RADIATION ONCOLOGY GUIDELINES

Transcription

1 MedSolutions, Inc. Clinical Decision Support Tool Diagnostic Strategies This tool addresses common symptoms and symptom complexes. Requests for patients with atypical symptoms or clinical presentations that are not specifically addressed will require physician review. Consultation with the referring physician, specialist and/or patient s Primary Care Physician (PCP) may provide additional insight. RADIATION ONCOLOGY GUIDELINES Version 3.0 Effective: MedSolutions, Inc. Clinical Decision Support Tool for Radiation Oncology This version incorporates MSI accepted revisions prior to 12/31/2014 Common symptoms and symptom complexes are addressed by this tool. Requests for patients with atypical clinical presentations that are not specifically addressed will require physician review. Consultation with the referring physician may provide additional insight. CPT (Current Procedural Terminology) is a registered trademark of the American Medical Association (AMA). CPT five digit codes, nomenclature and other data are copyright 2015 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values or related listings are included in the CPT book. AMA does not directly or indirectly practice medicine or dispense medical services. AMA assumes no liability for the data contained herein or not contained herein MedSolutions, Inc. Radiation Oncology Guidelines

2 RADIATION ONCOLOGY GUIDELINES Radiation Oncology Guidelines ABBREVIATIONS 3 RO-Preface~PREFACE to the RADIATION ONCOLOGY GUIDELINES 4 RO-1~Central Nervous System 21 RO-2~Breast Cancer 26 RO-3~Lung and Other Thoracic Cancers 29 RO-4~Lymphoma 32 RO-5~Bone Metastasis (including radiopharmaceutical therapy) 34 RO-6~Cancers of the Upper Gastrointestinal System (Hepatic, Gastric, Pancreatic, Billiary) 36 RO-7~Prostate Cancer 38 RO-8~Proton Beam Therapy 41 RO-9~Head and Neck Cancer 43 RO-10~Gynecological Cancer (Vaginal, Vulvar, Uterine, Cervical) 46 RO-11~Sarcoma 50 RO-12~Rectal and Anal Cancer 52 REFERENCES 53 APPENDIX: RADIATION ONCOLOGY PROGRAM 2015 Code Update 65 Radiation Oncology Guidelines Version 3.0 RETURN 2 P age

3 IMRT CRT 2DRT PBT HDR LDR EBRT SRS SBRT MLC IORT IGRT Abbreviations for the Radiation Oncology Guidelines ABBREVIATIONS intensity modulated radiation therapy conformal radiation therapy or 3-dimensional radiation therapy or 3- dimensional conformal radiation therapy 2-dimensional radiation therapy or conventional radiation therapy proton beam therapy high dose rate brachytherapy low dose rate brachytherapy external beam radiation therapy stereotactic radiosurgery stereotactic body radiation therapy multileaf collimator intraoperative radiation therapy Image Guided Radiotherapy Radiation Oncology Guidelines Version 3.0 RETURN 3 P age

4 PREFACE TO THE RADIATION ONCOLOGY GUIDELINES PREFACE RO PREFACE-1 Guideline Development and General Use 5 RO PREFACE-2 Benefits, Coverage Policies and Eligibility 6 RO PREFACE-3 Clinical Information 7 RO PREFACE-4 Copyright and Trademark Information 7 RO PREFACE-5 Allowable Number of Treatments/Fractions 8 RO PREFACE-6 Radiation Treatment Modalities 8 RO PREFACE-7 CODING GUIDELINES for Specific Procedures 10 Radiation Oncology Guidelines Version 3.0 RETURN 4 P age

5 PREFACE TO THE RADIATION ONCOLOGY GUIDELINES RO PREFACE-1~Guideline Development and General Use MedSolutions, Inc. (MSI) has developed and maintains evidence-based, proprietary clinical guidelines to evaluate radiation oncology procedures. MSI reserves the right to update the guidelines periodically and conducts a formal review of the clinical guidelines annually. These guidelines have incorporated well known and widely accepted criteria and standards including those from medical societies such the American Society for Radiation Oncology (ASTRO), the Choose Wisely campaign s recommendations, the American College of Radiation Oncology (ACRO), and the National Comprehensive Cancer Network (NCCN) current peer-reviewed medical literature. Additional contributions from panels of renowned subject matter experts and community physicians have been incorporated. MedSolutions guidelines are updated annually as well as on an ad hoc basis if new technology or new uses of existing technology emerge. Medsolutions guidelines are also informed by health plan specific policies. To promote transparency, the current version of these guidelines is always available for review on the MedSolutions website ( Medsolutions Guidelines sources: o nationally accepted guidelines and consensus statements published by specialty societies and organizations (e.g., Choose Wisely, NCCN, ASTRO Guidelines, etc.) o published peer reviewed evidence-based clinical data o health plan medical policies (see RO-Preface-2 for more details) o practicing physicians from academic and community-based centers These clinical guidelines are not intended to replace good medical judgment but rather to augment medical decision-making pertaining to the selection of the most clinically appropriate procedure for a patient s medical condition. These guidelines are written to describe appropriate general management of defined medical conditions; however, these guidelines may not be applicable in all clinical presentations of a defined medical condition, and physician judgment may then override the management recommended by these guidelines. The health care provider retains final authority and responsibility on all decision making related to patient care. Radiation Oncology Guidelines Version 3.0 RETURN 5 P age

6 PREFACE TO THE RADIATION ONCOLOGY GUIDELINES RO PREFACE-2~Benefits, Coverage Policies and Eligibility Benefits, coverage policies, and eligibility issues pertaining to each Health Plan (payor) may take precedence over MedSolutions guidelines. Providers are urged to obtain current written instructions, clinical policy bulletins and all other requirements directly from each payor. Current information can often be found via the individual payor s website. Medicare Coverage Policies For Medicare and Medicare Advantage enrollees, National Coverage Determinations (NCDs), the coverage policies of CMS (Centers for Medicare and Medicaid Services), may take precedence over MedSolutions guidelines. Regional Medicare Administrative Contractors (MACs) process Medicare claims within their jurisdictions and establish and maintain additional policy information through Local Coverage Determination (LCDs). LCDs, where available and active, may take precedence over MedSolutions guidelines. Providers are encouraged to submit MAC documentation for specific requests, particularly when LCD policy may take precedence over Medsolutions Guidelines. Investigational and/or Experimental Studies Certain forms of advanced imaging or radiotherapy described in these guidelines are considered investigational and/or experimental by various payors, and their coverage policies may take precedence over MedSolutions guidelines. Clinical and Research Trials Similar to investigational and experimental studies, clinical trial imaging and therapy requests will be evaluated to determine whether they meet Health Plan and MedSolutions evidence-based guidelines. Providers are encouraged to review the current medical/clinical coverage policies for each payor. Medsolutions guidelines incorporate state and federal legislation in the review of advanced imaging and radiotherapy requests. Radiation Oncology Guidelines Version 3.0 RETURN 6 P age

7 PREFACE TO THE RADIATION ONCOLOGY GUIDELINES RO PREFACE-3~Clinical Information MSI guidelines use a medical evidence-based approach to determine what procedures are appropriate, following submission by a provider for a course of radiotherapy. MSI guidelines pertain to the patient s overall health needs and not to any specific treatment equipment or technique. Providers should request specific procedures after an initial patient consultation, at which time the physician should have developed an overall treatment plan that may include a course of radiation therapy. Consultation provides current oncologic clinical information which may include signs and symptoms, history, physical examination findings, staging information, imaging and pathology reports. Such information is necessary for determining the medical necessity of radiation therapy requests. Clinical information provided to MSI must be sufficient to establish a clinical basis for each of the requested procedures. Additionally, each non-clinical (technical or ancillary) procedure and amount requested must be relevant to the radiotherapy requested and supported by the submitted documentation. RO PREFACE-4~Copyright and Trademark Information 2015 MedSolutions, Inc. All rights reserved. No part of these materials may be changed, reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying or recording, or in any information storage or retrieval system, without the prior expressed written permission of MSI. These guidelines abstract coding information from the 2014 and/or 2015 Physicians Current Procedural Terminology CPT manual. This information should not be used in place of the CPT manual. CPT five digit codes, nomenclature and other data are Copyright 2012 American Medical Association (AMA). All Rights Reserved. (No fee schedules, basic units, relative values or related listings are included in CPT. AMA does not directly or indirectly practice medicine or dispense medical services. The AMA assumes no liability for the data contained herein or not contained herein.). CPT is a registered trademark of the AMA. Radiation Oncology Guidelines Version 3.0 RETURN 7 P age

8 PREFACE TO THE RADIATION ONCOLOGY GUIDELINES RO PREFACE-5~Allowable Number of Treatments/Fractions Representations in these guidelines concerning allowable number of fractions are intended to be an allowable maximum for most indications discussed. It is understood that in most circumstances of curative treatment, a conventional fractionation of Gy daily is utilized for external beam radiotherapy unless otherwise stated in these guidelines. In most cases of palliative treatment, larger external beam dose fractions given in fewer fractions would be expected to expedite symptom relief and are consistent with national guidelines such as ASTRO s Choose Wisely. Allowable fractionation for stereotactic radiotherapy and brachytherapy can vary widely according to disease site and treatment modality, and additional detail is provided within the pertinent disease and modality sections of these guidelines. Exceptions to the allowable number of treatment fractions are uncommon. Such requests are reviewed on a case by case basis, and require complete supporting documentation to be submitted Personnel responsible for coding and/or billing are reminded that treating facilities and professionals may only code/bill for procedures actually performed, rather than for procedures authorized. RO PREFACE-6~Radiation Treatment Modalities Radiation therapy broadly includes External Beam Radiation Therapy (EBRT), Brachytherapy, Stereotactic Radiotherapy and Brachytherapy alone or combined with EBRT for select cases. o EBRT includes Intensity Modulated Radiation Therapy (IMRT), Conformal 3D Radiation Therapy (CRT) and 2D Radiation Therapy (2DRT) modalities. o Brachytherapy includes High Dose Rate (HDR) and Low Dose Rate (LDR) modalities for interstitial, intracavity or intraluminal means of treatment delivery. o Stereotactic Radiotherapy includes Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiation Therapy (SBRT) modalities. Regarding CRT and 2DRT: For the purposes of these guidelines, the terms "Conformal Radiation Therapy" and "3D Therapy" are interchangeable, since the allowable treatment planning and delivery codes for these procedures are interchangeable. Likewise, "2D Radiation Therapy" and Conventional Radiation Therapy are interchangeable, since the allowable treatment planning and delivery codes for these procedures are interchangeable. Though treatment delivery codes for both CRT and 2DRT are common to both forms of external beam therapy, each form of external beam therapy reports different treatment planning codes. Regarding IMRT: This sophisticated modality of highly conformal external beam therapy may be indicated for cases where there is clinical need to treat a target volume Radiation Oncology Guidelines Version 3.0 RETURN 8 P age

9 such that any of the following conditions are met. o Clinically meaningful dose homogeneity is achieved. o Treatment area is adjacent to previously irradiated fields. o Dose tolerances of surrounding tissue can be maintained. IMRT procedure requests must meet the requirements of the published CPT language for simple or complex IMRT delivery (CPT or CPT respectively). Beginning Jan 1, 2015 IGRT is bundled into the delivery code for IMRT and is not billable as a separate procedure. Teletherapy and brachytherapy are the codes that did change. Regarding SRS and SBRT: o SRS utilizes linear accelerators (including TomoTherapy and Cyberknife ) as well as cobalt based Gamma Knife for treatment delivery. o SBRT only utilizes linear accelerators for treatment delivery. Radiation Oncology Guidelines Version 3.0 RETURN 9 P age

10 PREFACE TO THE RADIATION ONCOLOGY GUIDELINES RO PREFACE-7 CODING GUIDELINES for Specific Procedures 7.1 Special Treatment Procedure Basic Radiation Dosimetry Calculation Special Physics Consultation MLC (Multi-Leaf Collimator) Treatment Device Procedure Codes Treatment Planning and Case Complexity 20 Radiation Oncology Guidelines Version 3.0 RETURN 10 P age

11 PREFACE TO THE RADIATION ONCOLOGY GUIDELINES RO PREFACE-7~CODING GUIDELINES for Specific Procedures RO PREFACE-7.1 Special Treatment Procedure Definition: CPT Special treatment procedure (ie, total body irradiation, hemibody radiation, per oral or endocavitary irradiation). o A special treatment procedure would be generally reported in addition to clinical treatment planning and is reported only once per course of therapy. o The medical record must specifically reflect the additional time and effort to justify coding a special treatment procedure in addition to clinical treatment planning. o A consultation note, treatment prescription and other medical chart documentation typically support coding a special treatment procedure. Providers must submit a unique separate note highlighting the requirements of being met if there is not documentation otherwise clearly provided for elsewhere within the submitted case documents. o The use of IGRT does not justify reporting of special treatment procedures. o The sole use of check boxes for documentation support is not sufficient. A special treatment procedure should never be automatically requested or billed. A special treatment procedure must be billed on the date documented in the patient medical record. o The professional and technical components of CPT must be reported on the same date of service. o It is expected that CPT special treatment procedure will be used infrequently relative to the overall radiotherapy treatment population. Specific clinical and coding guidance: the following represents common but not a comprehensive set of clinical scenarios where a special treatment procedure should not be reported routinely. o Providers should not report this procedure for administering hormone therapy, amifostine or other non-chemotherapy or non-cytotoxic chemotherapy agents in absence of concurrent chemoradiotherapy. o Providers should not report this procedure in the setting of sequential chemoradiotherapy (i.e., chemotherapy precedes or follows but does not overlap radiotherapy administration) o Providers should not report this procedure only on the basis that the patient has another, concurrent medical diagnosis (i.e., diabetes, COPD, hypertension, among others) that may impact the patient s tolerance to radiotherapy. o Providers should not report this procedure to indicate a modification of a course of treatment that would otherwise be described through reporting of other services (i.e., simulation, dosimetry, quality assurance, etc.) Radiation Oncology Guidelines Version 3.0 RETURN 11 P age

12 References 1. CPT Assistant, Winter CPT Assistant, October The ASTRO/ACR Guide to Radiation Oncology Coding 2010 Radiation Oncology Guidelines Version 3.0 RETURN 12 P age

13 PREFACE TO THE RADIATION ONCOLOGY GUIDELINES RO PREFACE-7~CODING GUIDELINES for Specific Procedures RO PREFACE-7.2 Basic Radiation Dosimetry Calculation Definition: CPT Basic radiation dosimetry calculation, central axis depth dose calculation, TDF, NSD, gap calculation, off axis factor, tissue inhomogeneity factors, calculation of nonionizing radiation surface and depth dose, as required during course of treatment, only when prescribed by the treating physician. Dosimetry is the mathematical calculation of the radiation dose distribution within a tumor site or a given treatment volume. This calculation may be performed by hand or computer, and by a medical physicist, dosimetrist or radiation therapist. There is both a professional and technical component for basic dosimetry services. One unit of basic dosimetry is appropriately billed for each unique MU calculation. o This code is typically billed once per port for standard external beam. o There is no separate charge for a tissue inhomogeneity calculation. o Multiple control points are not charged as separate units of basic dosimetry when the fields are merged into a single MU calculation. o Mirror image calculations (ie, same MU and/or same prescription point depth) completed for a pair of opposed ports are billed as one unit. o Only calculations used for patient treatment should be billed; any calculations retained in the record and not used should be clearly notated as not used. Specific clinical and coding guidance: the following represents common but not a comprehensive set of clinical scenarios where basic dosimetry calculations may or may not be routinely reported. Basic dosimetry calculations are appropriately repeated during a course of radiation therapy when: o There are changes in the patient s weight or girth. o There are new treatment targets. o The tumor volume or conformation has changed significantly. o A medically necessary boost field will be created that is different in size and shape from the original plan. Basic dosimetry calculations may be reported for IMRT, SRS or SBRT treatments but not for teletherapy CPT 77306, CPT (2D) or brachytherapy CPT 77316, CPT or CPT isodose plans. o Calculations are appropriately reported at a frequency of one unit per gantry angle, arc or path, unless considered inclusive of the dosimetry plan by the payor. Many payors have payment policies that cap the allowable number of basic dosimetry calculations during a course of treatment. Written payor policies and guidelines take precedence over MSI guidelines. Radiation Oncology Guidelines Version 3.0 RETURN 13 P age

14 References 1. CPT Assistant, Fall 91:14 2. CPT Assistant, Oct 97:3 3. CPT Assistant, Dec 08:9 4. CPT Assistant, Nov 09:3 5. CPT Changes: An Insider s View The ASTRO/ACR Guide to Radiation Oncology Coding 2010 Radiation Oncology Guidelines Version 3.0 RETURN 14 P age

15 PREFACE TO THE RADIATION ONCOLOGY GUIDELINES RO PREFACE-7~CODING GUIDELINES for Specific Procedures RO PREFACE-7.3 Special Physics Consultation Definition: CPT Special medical radiation physics consultation This code is reported when the radiation oncologist requests medical physics assistance, analysis and/or explanation for a specific problem or concern. It is expected that a qualified medical physicist, upon consultation request, will spend considerable time and effort on behalf of a specific patient. The medical physicist will provide a customized written report to the radiation oncologist referable to the specific problem being analyzed. o This report should not be a cloned note or completed template. It is a distinct document created by the medical physicist for a patient-specific problem or concern. o Generally, only one such report will be required for a course of therapy. o The radiation oncologist is then expected to review the report and use its findings to appropriately design or modify the current treatment plan. o A dose summary prepared for informational purposes but not used for patient treatment is not considered a special physics consultation for purposes of reporting this service. Specific clinical and coding guidance: the following represents common but not a comprehensive set of clinical scenarios where special physics consultation may not be routinely reported: o for any complex treatment, such as brachytherapy (ie. Tandem and ovoids or cylinder), IMRT, SBRT or SRS planning procedures, or o for quality assurance and verification of any treatment plan. Specific clinical and coding guidance: the following represents common but not a comprehensive set of clinical scenarios where special physics consultation may be routinely reported: o analysis of the effects of previous courses of radiation therapy with calculation of cumulative radiation dose to critical organs o computation of dose to the fetus of a pregnant patient undergoing radiation therapy o treatment plan development for multiple targets with abutting or overlapping fields and treated simultaneously o analysis and recommendations for transplanted organ protection o special brachytherapy devices developed by a qualified medical physicist to treat a particular patient (for example, unique custom templates) o unique circumstances that require greater than normal physics consultation effort, when supported by submitted provider documentation Radiation Oncology Guidelines Version 3.0 RETURN 15 P age

16 References 1. CPT Assistant, Fall 91:14 2. CPT Assistant, Oct 97:4 3. CPT Assistant, May 09:8 4. Clinical Examples in radiology Summer 08:12 5. CPT Changes: An Insider s View The ASTRO/ACR Guide to Radiation Oncology Coding 2010 Radiation Oncology Guidelines Version 3.0 RETURN 16 P age

17 PREFACE TO THE RADIATION ONCOLOGY GUIDELINES RO PREFACE-7~CODING GUIDELINES for Specific Procedures RO PREFACE-7.4 MLC (Multi-Leaf Collimator) Treatment Device Requesting providers should use the appropriate level of complexity. Non-IMRT o Multi-leaf collimator (MLC) devices can either be simple (CPT 77332), intermediate (CPT 77333), or complex (CPT 77334). o This code set is appropriately used to report MLC devices for non-imrt therapy. IMRT o MLCs may be used to construct a beam-modulating device for an IMRT treatment plan and may be reported once per IMRT plan using CPT o CPT may not be reported for physical compensator based IMRT (use CPT 77334). o Cases requiring cone down fields using IMRT are permitted to bill a second CPT when such requests are supported by documentation (see RO PREFACE-7.6) References 1. CPT Changes: An Insider s View 2010 Radiation Oncology Guidelines Version 3.0 RETURN 17 P age

18 PREFACE TO THE RADIATION ONCOLOGY GUIDELINES RO PREFACE-7~CODING GUIDELINES for Specific Procedures RO PREFACE-7.5 Procedure Codes Providers may reference a complete summary of code changes for 2015 in the Appendix: RADIATION ONCOLOGY PROGRAM 2015 Code Update. CLICK HERE Image Guided Radiotherapy (IGRT) CPT Providers are reminded that IGRT procedures are included in all the 2015 IMRT and SBRT delivery codes. IGRT can be requested when field sizes are small, with close margins (PTV) being used to minimize normal tissue exposure, and when daily visualization is necessary to ensure optimal accuracy. For example, where a small peripheral lung tumor is being treated with a postage stamp type field using 3D, IGRT would be considered a covered request. Intensity Modulated Radiotherapy (IMRT) Complexity Providers requesting IMRT should use the appropriate level of complexity as defined by the criteria below. Note that all guidance and tracking (IGRT) is included regardless of number or format used (Calypso, ultrasound, kv, MV, etc.): o Simple (CPT 77385): Any of the following: prostate, breast, and all sites using physical compensator-based IMRT (Note for 2015, Category III code 0073T is no longer reported) o Complex (CPT 77386): Includes all other sites, non-physical compensator based IMRT Conventional Radiotherapy Complexity (2D, 3D) Providers requesting conventional treatment delivery should use the appropriate level of complexity as defined by the criteria below: o Simple (CPT 77402): Radiation treatment delivery, >1MeV; and all of the following criteria are met: single treatment area, one or two ports and two or fewer simple blocks o Intermediate Treatment Delivery (CPT 77407): Radiation treatment delivery, >1MeV; and any of the following criteria are met (and none of the complex criteria are met): two separate treatment areas, three or more ports on a single treatment area, or three or more simple blocks o Complex (CPT 77412): Radiation treatment delivery, >1MeV; and any of the following criteria are met: three or more separate treatment areas, custom blocking, tangential ports, wedges, rotational beam, field in field or other tissue compensation that does not meet IMRT guidelines, or use of electron beam Radiation Oncology Guidelines Version 3.0 RETURN 18 P age

19 Brachytherapy and 2DRT The 2015 isodose plan codes below, used for brachytherapy and 2DRT, include basic dosimetry calculations; CPT should not be reported with these codes. o Isodose Plan, Simple (CPT 77316): calculations made from 1 to 4 sources or remote afterloading device 1 channel o Isodose Plan, Intermediate (CPT 77317): calculations made from 5 to 10 sources or remote afterloading device 2 to 12 channels o Isodose Plan, Complex (CPT 77318): calculations made from over 10 sources or remote afterloading device over 12 channels IMRT CPT Requests for multiple IMRT plans (CPT 77301) as a result of complex treatment planning will not be considered for approval unless all of the following occur: o an additional CT simulation with new images are acquired o both normal tissue target volumes and a tumor volume are redrawn o the clinical case supports such re-simulation due to significant changes in tumor volume and/or patient habitus Respiratory Motion (CPT 77293) This code represents the physician work and other resources involved in obtaining a respiratory correlated or 4-D CT simulation study for conformal treatment planning. This code must be billed with either code CPT or CPT on the same date of service, although the work may take place over multiple days. The work involved may include physicians, therapists, dosimetrists and physicists and has both a professional and a technical component. The work is performed in both the simulator and dosimetry. Thus, the work is part of the simulation and isodose planning process, not part of treatment delivery. Therefore, requests for CPT should never be requested for the purposes of reporting use of IGRT. Radiation Oncology Guidelines Version 3.0 RETURN 19 P age

20 PREFACE TO THE RADIATION ONCOLOGY GUIDELINES RO PREFACE-7~CODING GUIDELINES for Specific Procedures RO PREFACE-7.6 Treatment Planning and Case Complexity As stated earlier in the guidelines, the lowest case complexity to achieve satisfactory clinical target coverage while reasonably minimizing normal tissue toxicity is preferred. Many cases will require cone down(s) or boost(s), however, this does not necessarily support the use of additional treatment plans or repeat CT simulation. For example, after completing EBRT for breast, a boost to the tumor bed using electrons or photons may be used; however, neither will support the use of an additional plan and billing of CPT or CPT The target is small and normal tissue tolerance can be determined from the previously acquired simulation imaging. Isodose or electron calculations for the boost are permitted however. Similarly, for prostate cancer cases, a single plan may be utilized for cone downs involving pelvic, seminal vesicle and prostate targets. The subsequent cone down target(s) following pelvic radiotherapy (i.e., seminal vesicles, prostate) are typically unchanged, and therefore, no repeat CT simulation will be covered. Multiple devices may however be charged for the unique MLC fields used during the cone down, when supported by appropriate documentation Palliative cases should typically require a single modality. Palliative cases should also treat multiple targets within a given site on the same day whenever possible. For example, a patient with multiple brain mets should receive SRS to all sites for each treatment delivery request. Sequential treatment that extends the number of treatment days typically provides no clinical benefit but substantially increases overall treatment cost. Radiation Oncology Guidelines Version 3.0 RETURN 20 P age

21 RO-1.0 General Considerations RADIATION ONCOLOGY GUIDELINES RO-1~CENTRAL NERVOUS SYSTEM This guideline covers malignant and benign tumors of the brain and spinal cord in addition to other non-neoplastic conditions of the central nervous system for which radiation therapy may be indicated. Radiation therapy modalities used to treat tumors and other non-neoplastic conditions of the central nervous system most commonly include EBRT and SRS. RO-1.1 Non-Neoplastic Conditions Common non-neoplastic conditions responsive to radiotherapy include intracranial arteriovenous malformations (AVM), cerebral aneurysms, hemangiomas and trigeminal neuralgia. Stereotactic Radiosurgery SRS is appropriate for any of these conditions, provided that the target(s) is/are small and for a single fraction. RO-1.2 Low Grade Malignant and Benign Brain Tumors CRT and IMRT are indicated for any of these malignant or benign conditions, and stereotactic therapy may be prescribed for selected benign lesions. Stereotactic Radiosurgery/Radiotherapy SRS (1 fraction) or Fractionated Stereotactic Radiotherapy (up to 5 fractions) is considered appropriate for the following benign neoplastic indications when the target is 4 cm: o acoustic neuroma o meningioma: either recurrent after prior resection, grossly residual after current resection attempt or inoperable o pituitary adenoma, pinealoma, or craniopharyngioma CRT or IMRT CRT or IMRT can be authorized up to 33 fractions for meningioma, either recurrent after prior resection, grossly residual after current resection attempt or inoperable. CRT or IMRT can be authorized up to 30 fractions for the following indications: o low grade malignant glioma: recurrent after prior resection, grossly residual after current resection attempt or inoperable o pituitary adenoma, pinealoma, or craniopharyngioma Radiation Oncology Guidelines Version 3.0 RETURN 21 P age

22 References 1. Int J Radiat Oncol Biol Phys 2007;68: J Clin Oncol 2002;20: Int J Radiat Oncolo Biol Phys 1996;36: RO-1.3 High Grade Malignant Brain Tumors Stereotactic therapy is not indicated for previously untreated cases. For cases that have recurred following EBRT and retain good performance status, stereotactic therapies may be indicated to impair further disease progression. CRT or IMRT For high grade glioma, including anaplastic astrocytoma, anaplastic oligodendroglioma and glioblastoma multiforme, authorization may include up to 34 total fractions. For high grade ependymoma and medulloblastoma, authorizations may be include the following: o Two separate, concurrent courses (for whole brain and spinal cord, respectively) of CRT up to 20 fractions for a total dose of 36 Gy followed by: o Up to an additional 15 boost fractions of either CRT or IMRT to the site of original intracranial disease to a total dose of 63 Gy. o If gross spinal cord disease were noted at presentation, then an additional 5 boost fractions of either CRT or IMRT for a total dose of 45 Gy to site(s) of spinal disease may be allowed. Stereotactic Radiosurgery/Radiotherapy SRS (1 fraction) and Fractionated Stereotactic Radiotherapy (up to 5 fractions) are each considered appropriate for high grade malignant tumors only in the setting of small volume ( 4 cm maximum diameter) recurrent disease when surgical resection is not feasible. Lymphoma of the central nervous system is considered separately from other high grade malignant brain tumors. Elderly patients without history of immunocompromise achieving complete response following chemotherapy may be observed and treated with radiotherapy at progression. All other patients may be treated immediately following chemotherapy. Total prescribed dose for these cases is commonly Gy. IMRT is not required as the total prescription dose does not exceed tolerance doses of normal intracranial structures. 2DRT or CRT Authorization may include up to 25 fractions. Radiation Oncology Guidelines Version 3.0 RETURN 22 P age

23 References 1. Int J Radiat Oncol Biol Phys 2008;71(4): Int J Radiat Oncol Biol Phys 1996;36: Int J Radiat Oncol Biol Phys 2005;63: Neurology 1980;30(9): Int J Radiat Oncol Biol Phys 2004;60: Int J Radiat Oncol Biol Phys 2012;82: Radiation Oncology Guidelines Version 3.0 RETURN 23 P age

24 RO-1.4 Metastatic Disease to the Brain For patients never previously treated with radiotherapy for metastatic brain disease: In general, patients presenting with more than four brain metastases are most appropriately treated with whole brain irradiation alone, given the dosimetric restrictions of treating such patients stereotactically and overall poor prognosis. Commonly, schedules of 30.0 Gy in 10 fractions and Gy in fractions are prescribed for these cases. Patients presenting with a single brain metastasis appear to benefit from aggressive local treatment of the lesion. Whole brain irradiation alone results in suboptimal disease control for this patient group but may be offered in the setting of poor performance status and/or widely uncontrolled extracranial disease. Patients presenting with 2 4 brain metastases represent a more heterogeneous cohort with respect to technical and prognostic factors impacting decisions for modality selection. Additionally, prospective data to guide clinical decision-making is limited in this setting. In general, these patients may be treated with whole brain irradiation. A subset of these patients with control of extracranial disease, at least good overall performance status and limited intracranial tumor volume may be considered for stereotactic radiosurgery alone or with external beam radiotherapy. For patients previously treated with radiotherapy for metastatic brain disease: Patients previously treated with whole brain radiotherapy may be considered for SRS when extracranial disease is controlled, or when such treatment may reduce acute neurological deficits in patients with poor prognosis. Patients previously treated with stereotactic and other partial brain therapies may be treated with whole brain irradiation. Highly selected patients previously treated with whole brain therapy presenting with significant neurologic symptoms and poor short-term prognosis may be considered for whole brain re-irradiation. Stereotactic Radiosurgery/Radiotherapy SRS (1 fraction) and Fractionated Stereotactic Radiotherapy (up to 5 fractions), either as a monotherapy or as a boost therapy, can be authorized in patients with all of the following: o One to four metastatic brain lesions with no one lesion measuring greater than 4 cm, and/or the total volume of lesions < 34 cc, and o Controlled systemic disease, and KPS > 70 2DRT and CRT Whole Brain Irradiation 2DRT and CRT up to 15 fractions may be authorized for all other cases of brain metastases where whole brain irradiation is prescribed. CRT and IMRT Partial Brain Irradiation o CRT or IMRT for non-stereotactic boost of four or fewer lesions following whole brain irradiation can be authorized for up to 10 fractions. o CRT or IMRT for partial brain irradiation of relapsed disease following prior whole brain irradiation can be authorized for up to 20 fractions. Radiation Oncology Guidelines Version 3.0 RETURN 24 P age

25 References 1. Int J Radiat Oncol Biol Phys 1980;6: Int J Radiat Oncol Biol Phys 1981;7: Int J Radiat Oncol Biol Phys 1997;39: Int J Radiat Oncol Biol Phys 1997;37: JAMA 1998;280: NEJM 1990;322: Int J Radiat Oncol Biol Phys 1994;28: Int J Radiat Oncol Biol Phys 2002;53: Lancet 2004;363: Int J Radiat Oncol Biol Phys 2000;47: Cancer 1996;78: Radiation Oncology Guidelines Version 3.0 RETURN 25 P age

26 RO-2.0 General Considerations RADIATION ONCOLOGY GUIDELINES RO-2~BREAST CANCER Radiotherapy is used in the adjuvant setting in the management of breast cancer in order to sterilize residual microscopic disease remaining in the breast parenchyma, musculoskeletal chest wall, skin of the chest wall and/or regional lymphatics following surgery. The appropriate target volume selected for treatment varies according to the extent of surgery and disease. In rare cases, radiotherapy may be used in the definitive setting for technically or medically inoperable patients or may be used in the neoadjuvant setting for locally advanced cases in order augment disease response to chemotherapy and facilitate subsequent resection. RO-2.1 Post-Lumpectomy Radiotherapy This group of patients has been surgically treated with the intent of preserving breast parenchyma for the purpose of optimizing cosmetic outcome following cancer treatment. Patients with primary tumors small enough to permit local resection with negative margins and achieve an acceptable cosmetic outcome are considered appropriate for breast conservation surgical therapy. Other breast conserving surgical procedures include quadrantectomy and partial mastectomy. For patients treated with lumpectomy, adjuvant whole breast irradiation using conventional fractionation is indicated to reduce the risk of local disease recurrence. Additional clinical and technical considerations include the following: o Selected patients may be considered appropriate for hypofractionated radiotherapy if the following factors are present: age 50 years, pathologic stage T1-2N0 disease, no chemotherapy and low (± 7%) dose inhomogeneity in the central axis plane (see ASTRO Choosing Wisely #1). o Hypofractionated short course whole breast radiotherapy is typically 42.5 Gy delivered in 16 fractions, with boost optional. This treatment technique has long term data showing equivalence to standard fractionation o A boost to the lumpectomy cavity may be indicated to enhance local disease control rates. Boost may follow either conventionally fractionated or hypofractionated radiotherapy to the whole breast. Patients with high risk factors for local failure following surgery and adjuvant whole breast irradiation including age < 50 years, close or positive surgical margins or node-positive disease are particularly benefited by boost therapy. Electron beam radiotherapy is most commonly utilized to deliver a boost dose, although tangential (i.e. mini tangents) and other photon beam arrangements may be used instead for deepseated surgical cavities. Brachytherapy boosts LDR, HDR or IORT Radiation Oncology Guidelines Version 3.0 RETURN 26 P age

27 (Mammosite, Axxent, etc.) are not considered medically necessary when megavoltage electron and photon alternatives are available. o Specific clinical and coding guidance: When performing a breast boost to the surgical bed, either a teletherapy isodose planning request (with bundled dose calculation, CPT or CPT 77307) or CPT special teletherapy port plan, may be used depending on the modality (photons, electrons) selected. o Concurrent treatment of the regional lymphatics is indicated for selected patients. Although controversy remains as to precise selection criteria for nodal radiotherapy, a general consensus of high-risk factors for regional disease recurrence may include the following: 4 pathologically axillary positive lymph nodes, extracapsular nodal disease extension and/or no pathologic assessment of axillary nodal status. o Although controversial, adjuvant radiotherapy may be omitted for selected elderly patients (age > 70, favorable tumor characteristics, and minimal tumor size) with significant medical comorbidities who are surgically treated with lumpectomy for favorable, early-stage breast cancer. Considerations for IMRT will include review of the following factors in making determinations: o Breast size: patients with large intact breast volumes for who adequate dose homogeneity cannot be achieved with CRT techniques may be considered for IMRT. o Proximity of cardiac structures (for left-sided disease only): patients with history of cardiac disease and/or cardiotoxic systemic therapy and inadequate dose sparing with CRT techniques may be considered for IMRT. o Prior radiotherapy to an adjacent or overlapping treatment site: such patients are considered appropriate for IMRT. o IMRT should not be routinely used to treat whole breast as part of breast conservation therapy (see ASTRO Choosing Wisely #5). Selected early stage patients treated with lumpectomy may be offered accelerated partial breast irradiation (APBI) in lieu of whole breast irradiation, delivered in 10 fractions over a 5 day period (twice per day). APBI is a more recent strategy in the adjuvant radiotherapy of breast cancer and intends to deliver a dose of radiation to a defined margin of breast tissue surrounding the lumpectomy cavity after surgery. The entire breast parenchyma is not the intended target with this approach. APBI may be delivered using EBRT or brachytherapy, although HDR is most commonly used and is more established. Preferable patient criteria for APBI include: o age > 50 years, o unifocal invasive ductal cancer < 2 cm in greatest dimension, o no positive adenopathy, negative surgical margins, o estrogen receptor positivity and no EIC or LCIS. Radiation Oncology Guidelines Version 3.0 RETURN 27 P age

28 Other newer brachytherapy modalities such as electronic brachytherapy (Axxent ), noninvasive image guided brachytherapy (Accuboost ) and intraoperative radiotherapy (IORT) are more recent applications for breast cancer and are considered investigational for the purposes of this guideline. Payor policy may supersede MedSolutions guidelines. CRT or IMRT Whole Breast Irradiation Up to 28 fractions for whole-breast +/- regional nodal treatment (where clinically indicated) and an additional 8 fractions for boost treatment are allowed. The boost fractions may be either CRT or electron beam radiotherapy. Accelerated Partial Breast Irradiation o HDR brachytherapy: up to 10 fractions are allowed RO-2.2 Post-Mastectomy Radiotherapy For selected patients treated surgically with mastectomy, adjuvant chest wall irradiation using a conventional treatment schedule is indicated in order to reduce the risks of locoregional disease recurrence and cancer-specific mortality. Mastectomy patients generally thought to benefit from adjuvant radiotherapy include those with pathologic findings such as primary tumor invasion of skin and/or chest wall structures and/or involvement of 4 axillary lymph nodes. Patients with pathologic TisNX, TisN0, T1N0, or T2N0 following mastectomy are generally not considered likely to benefit from adjuvant radiotherapy. Post-mastectomy radiotherapy is usually comprehensive and includes treatment of the musculoskeletal chest wall, chest wall skin and regional lymphatics (axillary, supraclavicular). EBRT is the standard radiotherapy modality technically indicated to treat these volumes. CRT or IMRT Chest Wall Irradiation Up to 28 fractions for whole-breast +/- regional nodal treatment and, for select cases, an additional 6 fractions for boost treatment are allowed. The boost fractions are typically expected to be delivered with electron beam radiotherapy only. References 1. Oncology 2009;23(4): J Natl Compr Canc Netw 2009;7: Int J Radiat Oncol Biol Phys 2009;74: Keisch M, Arthur D, Patel R, et al. American Brachytherapy Society Breast Brachytherapy Task Group. February 2007, N Engl J Med 2010;362: Int J Radiat Oncol Biol Phys 2010;Jul J Clin Oncol 2008;26: START trial, 2013 The Lancet Oncology, Vol. 14 No. 11 pp ) Radiation Oncology Guidelines Version 3.0 RETURN 28 P age

29 RADIATION ONCOLOGY GUIDELINES RO-3~LUNG and OTHER THORACIC CANCERS RO-3.0 General Considerations This disease group largely consists of non-small cell (NSCLC) and small cell lung cancers (SCLC) and also includes less common malignancies such as mesotheliomas and thymomas. Radiotherapy has multiple applications in the management of non-small cell and small cell lung cancers, depending on disease histology, stage and integration of other modalities into the overall course of care for the given patient. Broadly speaking, radiotherapy utilization for lung cancer may be categorized accordingly: o definitive radiotherapy for early-stage disease or solitary pulmonary nodule o definitive radiotherapy for locoregionally advanced, non-metastatic non-small cell lung carcinoma o definitive radiotherapy for limited stage small cell lung carcinoma o neoadjuvant or adjuvant radiotherapy for locoregionally confined non-small cell lung carcinoma o prophylactic cranial irradiation (PCI) for selected extensive stage small cell (ES- SCLC) carcinoma patients and all limited stage small cell carcinoma patients (LS- SCLC) RO-3.1 Definitive Radiotherapy of Early-Stage NSCLC Surgery is the preferred definitive treatment modality for early stage non-small cell lung cancer but may be contraindicated by patient medical comorbidities or patient choice. According to Choosing Wisely recommendation #7 for radiation oncology, do not offer radiation therapy for patients who have resected NSCLC negative margins NO-1 disease ( If medically inoperable, then EBRT or SBRT may be considered. Such patients should radiographically demonstrate a single focus of disease. Most patients should undergo assessment for mediastinal adenopathy prior to definitive parenchymal only radiotherapy. o For tumors < 5 cm, SBRT is the preferred radiotherapy modality. o For tumors > 5 cm, EBRT is the preferred modality normal lung tissue toxicity. SBRT regimen may vary depending on tumor location (i.e. central, peripheral, or adjacent to rib). Use of combined EBRT and boost SBRT for borderline large tumors is considered investigational and not supported in this guideline. CRT or IMRT Up to 37 fractions are approved. Up to 5 fractions are approved. SBRT Radiation Oncology Guidelines Version 3.0 RETURN 29 P age

30 RO-3.2 Definitive Radiotherapy of Locoregionally Advanced NSCLC CRT is expected to produce appropriate dosimetry for the majority of NSCLC cases. Patient and disease criteria for which IMRT may be considered include the following: o Superior sulcus involvement o Invasion of vertebral body, paraspinal disease involvement o Bilateral mediastinal involvement o Immediately adjacent or overlapping prior radiotherapy fields CRT or IMRT Up to 37 fractions for definitive treatment may be approved. RO-3.3 Definitive Radiotherapy of Limited Stage SCLC For limited stage small cell lung cancer, combined radiotherapy and chemotherapy represents the standard of care. CRT Up to 37 fractions for definitive treatment may be approved. RO-3.4 Neoadjuvant or Adjuvant Radiotherapy for Locoregionally Confined NSCLC Selected patients with stage III non-small cell disease may be treated with radiotherapy either (1) neoadjuvantly in order to cytoreduce borderline resectable disease and facilitate subsequent resection or (2) adjuvantly following surgery to treat grossly residual tumor and/or thoracic sites thought to be at high risk for harboring microscopically residual disease. CRT or IMRT For neoadjuvant radiotherapy: up to 28 fractions are approved. For adjuvant radiotherapy with negative margins and no grossly residual disease: up to 28 fractions are approved. For adjuvant radiotherapy with positive margins and/or grossly residual disease: up to 39 fractions are approved. Radiation Oncology Guidelines Version 3.0 RETURN 30 P age

31 RO-3.5 Prophylactic Cranial Irradiation (PCI) for SCLC Patients with limited stage SCLC and extensive stage SCLC may be considered for PCI. Extensive stage patients receiving PCI should have controlled extracranial disease. EBRT is directed to the entire brain and is delivered following completion of chemotherapy. Given the low doses commonly prescribed in this setting, IMRT is not considered necessary. Up to 10 fractions are approved. 2DRT or CRT RO-3.6 Other Thoracic Cancers Up to 30 fractions are approved. CRT or IMRT RO-3.7 Palliative Chest Radiotherapy For patients receiving palliative chest radiotherapy, up to 15 fractions may be approved using 2D or CRT. References 1. Lung Cancer 2010;69(2): Oncol 2011;22: Int J Radiat Oncol Biol Phys 2010;77(2): Int J Radiat Oncol Biol Phys 2010;78(3): Int J Radiat Oncol Biol Phys 2010;76(1): ASTRO stereotactic body radiation therapy (SBRT) model coverage policy. August 2, 2010, documents/sbrtmp.pdf. Accessed February 1, Int J Radiat Oncol Biol Phys 2010;77(2): J Natl Compr Canc Netw 2010 July;8(7): Int J Radiat Oncol Biol Phys 2009;75(3suppl):S3 10. SBRT for Lung Cancer: report of the ASTRO Emerging Technology Committee (ETC). January 1, 2010, pdf. Accessed February 1, N Engl J Med 1986;315: N Engl J Med 1999;340: N Engl J Med 2007;357: J Clin Oncol Aug 1; 30(22): doi: /JCO Epub 2012 Jul Jpn J Radiol Jun; 28(5): doi: /s x. Epub 2010 Jun Lancet Oncol May; 10(5): doi: /S (09) Epub 2009 Apr 20 Radiation Oncology Guidelines Version 3.0 RETURN 31 P age

32 RO-4.0 General Considerations RADIATION ONCOLOGY GUIDELINES RO-4~LYMPHOMA This disease group includes Hodgkins and non-hodgkins lymphoma. Radiotherapy is commonly used in stages I II intermediate grade non-hodgkins lymphoma and Hodgkin s disease as a consolidative treatment following chemotherapy to initial sites of disease presentation. For early-stage, low-grade non-hodgkins lymphoma and highly favorable cases of Hodgkins disease, radiotherapy may be used alone as a definitive treatment. RO-4.1 Hodgkins Disease EBRT is commonly prescribed for patients with stages I II disease following chemotherapy, and all sites of initial disease presentation are treated to the cytoreduced volume. Selected patients presenting with bulky stages III IV disease may be offered consolidative radiotherapy to initial sites of bulky involvement. Total doses are similar to those used for stages I II bulky disease and titrated according to chemotherapy response. Selected patients with highly favorable disease may be treated with EBRT alone. In absence of chemotherapy, initial field doses of Gy and boost field doses of 40 Gy and higher may be prescribed. Given the low doses used and concern for secondary tumor induction in these commonly younger patients, simple CRT field arrangements are preferred over IMRT. 2DRT or CRT For non-bulky disease following complete response to chemotherapy: up to 17 fractions. For bulky disease following complete response to chemotherapy: up to 20 fractions. For suboptimal response to chemotherapy or treatment with EBRT alone: up to 25 fractions. Radiation Oncology Guidelines Version 3.0 RETURN 32 P age

33 RO-4.2 Non-Hodgkins Lymphoma Use of radiotherapy in the management of follicular low grade lymphoma is highly individualized. Stages I II disease may be treated with EBRT alone or with consolidative EBRT to initial disease sites following systemic therapy. Dosing is commonly Gy using conventional fractionation. MALTomas of the stomach and other sites is commonly treated with EBRT alone to doses of Gy. Mantle cell lymphoma, diffuse large cell B-cell lymphoma and peripheral T-cell lymphoma are commonly treated with chemotherapy followed by consolidative EBRT for stages I II disease. Chemotherapy alone is more commonly used in the management of advanced stage lymphomas. Radiation doses used in this setting are commonly Gy with higher doses prescribed for suboptimal chemotherapy response. Appropriate EBRT techniques for non-hodgkins lymphoma include 2DRT and CRT. Electron beam radiotherapy may be used for primary skin lymphomas and other superficial target volumes. Primary CNS lymphoma may be treated definitively with radiotherapy, and dose typically ranges from Gy depending on a variety of factors. 2DRT or CRT techniques are sufficient for most cases given the lower total dose used and preference to minimize integral dose. 2DRT or CRT For low grade lymphomas and MALTomas: up to 20 fractions is allowed. For other, more aggressive lymphomas: up to 25 fractions is allowed. Radioimmunotherapy: including Zevalin and Bexxar, may be indicated for the following: o CD20 positive newly diagnosed low grade B-cell lymphomas o relapsed low grade B-cell lymphomas refractory to Rituxan o transformed B-cell lymphomas o CD20-positive, intermediate-grade non-hodgkin s lymphoma following fullcourse CHOP-based chemotherapy References 1. J Clin Oncol 2009;27(27): Cancer 1993;71(7): J Clin Oncol 2005;23: N Engl J Med 2003;348: N Engl J Med 2010;363: Radiother Oncol 2006;79(3): J Clin Oncol 2004;22: N Engl J Med 1998;339: J Clin Oncol 2003:21: Cancer 2010;116: J Clin Oncol 2002;20: Radiation Oncology Guidelines Version 3.0 RETURN 33 P age

34 RADIATION ONCOLOGY GUIDELINES RO-5~BONE METASTASIS RO-5.1 General Considerations Multiple radiotherapy modalities are available in this setting, including EBRT, SBRT and radiopharmaceutical therapy. RO-5.1 EBRT Multiple prospective studies have evaluated a wide range of EBRT dose-fractionation schedules for these patients, and protracted fractionation (i.e., > 10 fractions) treatment courses have largely been found to no more effective than shorter courses in the degree and durability of pain palliation. This is supported by ASTRO s recommendation to Choosing Wisely (recommendation #3) states: Don t routinely use extended fractionation schemes (>10 fractions) for palliation of bone metastases. Patients with poor overall performance status may be treated with very short course treatment schedules (i.e., 5 fractions or fewer, or one fraction of 8 Gy), whereas selected favorable patients with multiple bone metastases may be considered for longer treatment courses (i.e., up to 15 fractions). In most cases, 2DRT is appropriate for treatment delivery due to the lower doses commonly delivered in this setting. CRT and IMRT will be considered for the following case types: o Immediately adjacent or overlapping radiotherapy treatment fields have been previously delivered for the patient o Only a single bone metastasis is identified by technetium or sodium fluoride-based whole-body skeletal imaging for a patient with otherwise good or excellent performance status o Patients with a significant extraosseous component of disease where conformal treatment may limit normal tissue toxicity EBRT Up to 10 fractions is allowed using 2DRT. RO-5.2 SBRT SBRT should not, per the ASTRO Task Force, be used as the primary treatment of vertebral bone lesions causing spinal cord compression. SBRT may be offered to patients with recurrent spinal disease following a prior course of EBRT where pain and/or clinical or radiographic evidence of spinal cord encroachment are present. SBRT is particularly useful in this setting to administer meaningful radiation dose while maintaining adequate sparing of the spinal cord. SBRT is not indicated for recurrent bone metastases involving non-spinal skeletal sites. Up to 5 fractions is allowed. SBRT Radiation Oncology Guidelines Version 3.0 RETURN 34 P age

35 RO-5.3 Radiopharmaceutical Therapy Radiopharmaceutical therapy may be used in the setting of diffuse and symptomatic bone metastasis not amenable to palliation with limited EBRT fields. o Strontium-89 and Samarium-153 are injectable agents indicated for patients with diffuse and symptomatic bone metastases secondary to prostate and breast cancer only for which treatment with local field external beam radiotherapy is not clinically practical. Prescribing physicians are advised to verify each patient considered for such therapy has adequate bone marrow reserves as per the manufacturers guidelines prior to ordering the agent for injection. o Radium-223 is an injectable agent indicated for patients with bone metastases secondary to prostate cancer only and with good or excellent performance status. Only 1 injection is allowed. Strontium-89 or Samarium-153 Radium-223 The following general clinical requirements are necessary prior to approval of the agent (more specific criteria are evaluated during the authorization process): o castrate-resistant disease with at least 2 skeletal metastases on imaging and no lung, liver or brain metastases (lymph node only metastasis is allowed) o symptomatic disease with radiographic or biochemical evidence of disease progression o adequate hematologic, liver and renal function: o no recent chemotherapy (within 4 weeks of request) o no prior hemibody radiotherapy A series of 6 monthly injections is allowed per the patient s lifetime. References 1. Int J Radiat Oncol Biol Phys 2011;79: Int J Radiat Oncol Biol Phys 2009;75: J Am Coll Radiol 2010;7: J Neurosurg Spine 2011;14: Int J Radiat Oncol Biol Phys 2003; 55: Choosing Wisely. ChoosingWisely%20List_FINAL_ pdf) Radiation Oncology Guidelines Version 3.0 RETURN 35 P age

36 RADIATION ONCOLOGY GUIDELINES RO-6~CANCERS of the UPPER GASTROINTESTINAL SYSTEM RO-6.0 General Considerations Tumor sites included in this group are esophageal, gastric, pancreatic, hepatic and biliary system cancer. With rare exception, EBRT is the sole radiation treatment modality used in the management of these tumors. EBRT may be used adjuvantly following attempt at curative resection or definitively for medically or technically inoperable cancers, often in conjunction with chemotherapy. SBRT may be considered for a few uncommon clinical scenarios: o For definitive treatment of small and medically inoperable hepatocellular carcinoma o For salvage of local recurrence of previous treated pancreatic cancer RO-6.1 Esophageal and Gastric Cancers Patients undergoing curative resection of esophageal and gastric cancers are often candidates for adjuvant chemoradiotherapy due to the high rate of locoregional and distant disease recurrence. Post-operative radiotherapy doses of Gy are commonly prescribed to address microscopic disease risk in the primary surgical bed and draining lymphatics. Patients with technically or medically unresectable disease without evidence of distant metastases may be considered for definitive chemoradiotherapy. Either CRT or IMRT is indicated to deliver higher radiation doses to achieve local disease control while limiting exposure to surrounding radiosensitive organs, including the heart, liver, small bowel, spinal cord and kidneys. CRT or IMRT For postoperative radiotherapy: up to 28 fractions is allowed. For definitive radiotherapy for unresectable disease: up to 30 fractions is allowed. Reference 1. J Natl Compr Canc Netw 2010;8(4): N Engl J Med 2001;345: RO-6.2 Pancreatic Cancer and Extrahepatic Cholangiocarcinoma Whether delivered with neoadjuvant, adjuvant or definitive intent, IMRT offers improved dosimetry that may help to spare the multiple radiosensitive organs and structures of the upper abdomen, including kidneys, small bowel and spinal cord. Palliative patients (with unresectable or metastatic disease) may receive 3DRT. Radiation Oncology Guidelines Version 3.0 RETURN 36 P age

37 SBRT for definitive treatment is considered investigational. However, SBRT may be offered for highly selected cases demonstrating all of the following: o local recurrence or persistent disease after prior attempt at curative surgery or radiotherapy o tumor 5 cm o no radiographic evidence of distant metastasis CRT or IMRT For adjuvant radiotherapy following curative resection: up to 28 fractions is allowed. For definitive radiotherapy for unresectable disease: up to 34 fractions is allowed. Up to 5 fractions is allowed. Reference SBRT 1. Int J Radiat Oncol Biol Phys 2010 Sep 22 Abstract 2. Cancer 1987;59: Cancer 1981;48: RO-6.3 Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma If used, radiotherapy is commonly offered for patients with localized but unresectable disease. Either CRT or IMRT is an appropriate radiation therapy modality in this setting where tumor is surrounded by multiple critical radiosensitive structures and where high radiation doses are needed to establish local disease control. SBRT may be considered for patients with medically unresectable and solitary hepatocellular carcinoma 5 cm. Up to 35 fractions is allowed. Up to 5 fractions is allowed. CRT or IMRT SBRT Radioactive Yttrirum-90 Microspheres Yttrirum-90 Microspheres use is permitted in accordance with FDA approved guidelines for unresectable liver metastases or hepatocellular carcinoma. Reference 1. J Natl Compr Canc Netw 2009;7: SIR-Spheres microspheres (Yttrium-90 Microspheres). Package insert. November Sirtex Medical Inc. Wilmington MA. U.S. Food and Drug Administration (FDA). TheraSphere. Humanitarian Device Exemptions. Updated January 4, Accessed September 9, U. S. Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH). Medical Device Reporting. Searched MAUDE Database for SIR-Spheres. Updated August 31, Accessed September 9, Radiation Oncology Guidelines Version 3.0 RETURN 37 P age

38 RO-7.0 General Considerations RADIATION ONCOLOGY GUIDELINES RO-7~PROSTATE CANCER The management of localized prostate cancer is controversial with regard to both the selection of treatment modality between surgery and radiotherapy and the need for treatment versus surveillance for early stage disease. ASTRO recommends that the management of low-risk prostate cancer management should not be initiated without discussing active surveillance (Choosing Wisely #2). For the purposes of selecting an appropriate treatment, several multi-tiered risk systems have been proposed. Each roughly assigns a risk level according to clinical stage, Gleason score and serum PSA at presentation. o Low risk disease may include patients with clinical stage T1 T2a disease, Gleason score of 5 6 and presenting PSA of < 10 ng/ml. These patients are often recommended monotherapy such as prostatectomy, external beam radiotherapy or brachytherapy alone. Select patients with anticipated survival of < 10 years may be offered active surveillance in lieu of definitive treatment. o Intermediate risk disease may include patients with clinical stage T2b T3 disease, Gleason score of 7 or presenting PSA of ng/ml. These patients are often recommended prostatectomy, combined hormonal deprivation therapy and external beam radiotherapy or combined external beam radiotherapy and brachytherapy. Unless the patient s overall performance status is chronically poor, active surveillance may not be recommended for this more advanced disease group. o High risk disease may include patients with clinical stage T3 T4 disease, Gleason score > 7 or presenting PSA of > 20 ng/ml. These patients are often recommended combined hormonal deprivation therapy and external beam radiotherapy. Select patients with small volume, high risk disease may be offered prostatectomy instead. Among radiotherapy modalities, EBRT, HDR brachytherapy and LDR brachytherapy represent standard treatment options. SBRT (e.g. Cyberknife ) is considered an investigational therapy within the context of these guidelines but may be supported as a standard of care by a given payor s medical policy and therefore authorized. RO-7.1 EBRT IMRT and CRT are both considered appropriate EBRT modalities for localized prostate cancer. Total prescribed doses with vary according to treatment intent, for example definitive versus salvage, and whether brachytherapy boost is planned. Combined EBRT and brachytherapy may be offered for patients with at least intermediate risk disease as defined by the criteria below. Combined modality therapy is Radiation Oncology Guidelines Version 3.0 RETURN 38 P age

39 not considered medically necessary for low-risk prostate cancer. Criteria for combined therapy include all of the following: o Pre-treatment prostate specific antigen (PSA) < 20 ng/ml o Gleason s score 7 or greater in multiple biopsy cores Adjuvant or salvage EBRT is indicated following definitive prostatectomy for any of the following pathologic findings: o Seminal vesicle involvement o Positive surgical margin o Extracapsular disease extension o Detectable or rising postoperative PSA Proton beam therapy has not demonstrated any disease or toxicity advantage over CRT or IMRT in a controlled study and is considered investigational. ASTRO s recommendation (Choosing Wisely #4) state: Don t routinely recommend proton beam therapy for prostate cancer outside of a prospective clinical trial or registry. Most payors also recognize proton treatment for prostate cancer as investigational. Payors may allow treatment when patients are enrolled on a national registry or national clinical trial. For additional details, please refer to section RO-8 Proton Beam Radiotherapy. CRT or IMRT For definitive radiotherapy of intact prostate cancer: up to 45 fractions allowed. For definitive radiotherapy of intact prostate cancer when combined with brachytherapy: up to 28 fractions allowed. For adjuvant radiotherapy following definitive prostatectomy with high-risk pathologic features: up to 38 fractions allowed. For adjuvant radiotherapy following definitive prostatectomy where there is gross residual disease, higher doses would be appropriate, up to 39 fractions For salvage radiotherapy of local recurrence following prior definitive prostatectomy: up to 40 fractions allowed. References 1. Int J Radiat Oncol Biol Phys 2010;76(2): J Clin Oncol 2007;25(15): JAMA 2008;299(23): JAMA 2006;296(19): J Urol 2009;181(3): Int J Radiat Oncol Biol Phys 2010:76(3): J Clin Oncol 2005;23(32): American Urological Association Prostate Cancer: guideline for the management of clinically localized prostate cancer: 2007 update. guidelines-and-qualitycare/clinical-guidelines/main-reports/proscan07/content.pdf. Accessed February 2, 2011Choosing Wisely. ChoosingWisely%20List_FINAL_ pdf). Radiation Oncology Guidelines Version 3.0 RETURN 39 P age

40 RO-7.2 Brachytherapy Either LDR or HDR brachytherapy as monotherapy is appropriate in the management of localized prostate cancer. LDR seed implant is always administered as a single operative procedure, whereas HDR may be administered with catheter placements and is typically delivered in several fractions over multiple days. Combined EBRT and brachytherapy is appropriate for at least intermediate risk disease but is considered medically not necessary for low risk disease. LDR or HDR As monotherapy: up to 6 HDR fractions or 1 LDR fraction allowed. As boost therapy: up to 4 HDR fractions or 1 LDR fraction allowed. References 1. Merrick GS, Zelefsky MJ, Sylvester J, et al. American Brachytherapy Society Prostate Low-Dose Rate Task Group. Not dated. therapy.org/guidelines/prostate_lowdoseratetaskgroup.pdf. Accessed February 2, Hsu IC, Yamada Y, Vigneault E, et al. American Brachytherapy Society Prostate High-Dose Rate Task Group. August 2008, therapy.org/guidelines/hdrtaskgroup.pdf. Accessed February 2, Int J Radiat Oncol Biol Phys 2010;76(2): Int J Radiat Oncol Biol Phys 2010 Jun 2 (E-pub ahead of print) 5. Int J Radiat Oncol Biol Phys 2004;59: Int J Radiat Oncol Biol Phys 2002;53: Radiation Oncology Guidelines Version 3.0 RETURN 40 P age

41 RO-8.0 General Considerations RADIATION ONCOLOGY GUIDELINES RO-8~PROTON BEAM THERAPY All requests for PBT will be sent for Medical Director review. Clinical trial coverage for proton beam therapy is solely at the discretion of the payors. If no payor policy exists, MedSolutions policy will be used which follows Medicare policy and ASTRO guidelines regarding use of proton therapy, and as further described below. ASTRO recommendation (Choosing Wisely #4):Don t routinely recommend proton beam therapy for prostate cancer outside of a prospective clinical trial or registry. Approved requests for PBT as a substitution for stereotactic radiosurgery will be authorized for the same fraction number as the stereotactic course but will substitute CPT for the treatment delivery code. RO-8.1 Specific Disease Considerations Prostate Cancer PBT is considered not medically necessary for localized prostate cancer. ASTRO recommendation (Choosing Wisely #4): Don t routinely recommend proton beam therapy for prostate cancer outside of a prospective clinical trial or registry. Lung and Upper Abdominal Cancers PBT is not indicated for the treatment of lung, pancreatic and other tumor sites subject to respiratory movement. Brain Tumors PBT is considered not medically necessary for this disease group. Ocular Melanoma PBT is considered medically necessary for the management of this disease. Stereotactic PBT has been performed for this specific indication. PBT has been utilized for several decades as an alternative to episcleral plaque brachytherapy for uveal melanoma with high rates of local disease control published. Spinal and Base of Skull Chordoma and Chondrosarcoma PBT is considered medically necessary in these settings. Radiation Oncology Guidelines Version 3.0 RETURN 41 P age

42 PBT has been used adjuvantly and definitively for technically unresectable disease in order to deliver adequate radiation doses to target volumes proximal to brain and spinal cord. Long-term results on its use and efficacy have been published. References 1. J Am Coll Radiol 2009;6: Ann Intern Med 2009;151: J Am Coll Radiol 2010;7: Oncology 2009;23: Radiother Oncol 2012;103: Radiother Oncol 2007;83: J Clin Oncol 2008;28: The Cancer J 2009;15: Int J Radiat Oncol Biol Phys 2011;81: Clin Lung Cancer 2012;13: Int J Radiat Oncol Biol Phys 2013;86: Choosing Wisely. ChoosingWisely%20List_FINAL_ pdf). Radiation Oncology Guidelines Version 3.0 RETURN 42 P age

43 RO-9.0 General Considerations RADIATION ONCOLOGY GUIDELINES RO-9~HEAD and NECK CANCER Radiation therapy is a common treatment modality in the management of head and neck cancers, both as a curative modality and as an adjuvant treatment following surgery. Fractionation can vary widely in head and neck radiotherapy. Conventional fractionation consists of daily fractions of Gy (2.0 Gy daily is generally preferred, particularly in cases where radiotherapy is the sole curative modality). When combined with chemotherapy, standard fractionation is typically utilized. Dose may vary within a plan from 54 to 72 Gy (for example, CTV low risk vs. gross disease) depending on the modality used. Maximum plan dose varies with overall stage and fractionation schedule. Altered fractionation, typically used without chemotherapy, may consist of either: o Twice-daily fractions throughout the course of treatment (ie, hyperfractionation to total doses of Gy using twice daily fractions); or o Twice-daily fractions during the boost portion of treatment only (ie, concomitant boost accelerated therapy to a total dose of 72 Gy delivered over 6 weeks) Although either IMRT or CRT may be used for most cases of head and neck cancer, IMRT is preferred in cases where treatment of the target volume with CRT may result in increased risks to the major salivary glands, temporal lobes, mandibles, auditory structures and optic structures as compared to IMRT. Occult Primary Head and Neck Cancer This designation refers to a squamous cell carcinoma presenting in cervical lymph node(s) and without evidence of either a primary disease site or distant disease, suggestive of an undetected primary site in the upper aerodigestive tract. This clinical diagnosis is potentially curative. Conversely, discovery of any other pathology, a positive radiographic finding below the neck, and/or a clinical finding or history suggesting another probable primary site suggests metastatic disease from a distant primary site. Metastatic disease is considered incurable, and therefore palliative therapy guidelines would apply. Requests for aggressive local control using higher curative dose radiotherapy will be sent for Medical Director review. References 1. Lancet Oncol 2010; 11: Br J Radiol 2009; 82: Ann Oncol 2010; 21 Suppl 5:v184-6.: v184-v Radiother Oncol 2009; 92:4. Pignon JP, le Maître A, Maillard E, et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiation Oncology Guidelines Version 3.0 RETURN 43 P age

44 RO-9.1 Definitive Radiotherapy CRT or IMRT is appropriate for all head neck primary tumors treated with definitive intent except for early stage glottis, early stage supraglottic and lip cancer, where non- IMRT techniques are more appropriate for these small and simple target volumes. Conventional fractionation is appropriate for all stages of disease. Locally advanced disease is typically treated with concurrent chemoradiotherapy. Alternate fractionation schedules may be considered for advanced stage disease, particularly when chemotherapy is omitted. CRT or IMRT Early Stage Disease may receive up to 74 Gy in 37 fractions using conventional fractionation. Early stage larynx T1-2N0 may receive up to 66 Gy at 2 Gy per fraction. Exception: for laryngeal cancers, the following dose schedules are appropriate and preferred in addition to standard fractionation as described above: o Tis (carcinoma in situ): Gy at 2.25 Gy per fraction o T1 2, N0: 62.5 Gy at 2.5 Gy per fraction or 63 Gy at 2.25 Gy per fraction. Late Stage Disease may receive up to 74 Gy in 37 fractions using conventional fractionation. Exception: for selected definitive cases treated with radiotherapy alone, doses up to ~ 81 Gy in 68 fractions using hyperfractionation and 72 Gy in 40 fractions using concomitant boost fractionation may be used instead. References 1. Radiother Oncol 2007; 85: Ann Oncol 2010; 21 Suppl 5:v184-6.: v184-v Cancer 2009; 115: Radiation Oncology Guidelines Version 3.0 RETURN 44 P age

45 RO-9.2 Adjuvant Radiotherapy Patients may require postoperative radiotherapy with any of the following risk factors for locoregional disease recurrence: o close or positive margins o pathologic N2-3 disease o cartilage invasion o nodal disease extracapsular extension (ECE) o nodal disease involving levels IV or V o pathologic T3 or T4 primary disease o perineural (PNI) or lymphovascular invasion (LVSI) CRT or IMRT Intermediate Risk patients with 1 above risk factor, excluding extracapsular extension should receive: 1.8 Gy fractions to a total dose of 57.6 Gy or 2 Gy fractions to a total dose of 60 Gy (maximum 32 fractions) High Risk patients with either 2 or more above risk factors or extracapsular extension: 1.8 Gy fractions to a total dose of 63 Gy or 2 Gy fractions to a total dose of 66 Gy (maximum 35 fractions) The benefit of postoperative concurrent chemoradiotherapy over postoperative RT alone has been demonstrated primarily for patients with positive surgical margins and/or extracapsular extension (e.g. EORTC/RTOG trial data). RO-9.3 Brachytherapy Brachytherapy as a monotherapy is appropriate for certain early stage lip and oral cavity tumors. Brachytherapy as a boost is appropriate after external beam radiotherapy for technically implantable lip and oral cavity tumors; brachytherapy boost for nasopharyngeal tumors is also appropriate but using intracavitary techniques instead. External beam radiotherapy doses of Gy using conventional fractionation are commonly used prior to brachytherapy boost. Brachytherapy dosing and fractionation may vary widely and are reviewed on a case-by-case basis. Oral cavity tumors with attachment to periosteum or with frank invasion of bone are contraindicated for brachytherapy given the high risk of osteoradionecrosis in this setting. References 1. Radiother Oncol 2007; 85: Ann Oncol 2010; 21 Suppl 5:v184-6.: v184-v Cancer 2009; 115: Int J Radiat Oncol Biol Phys 2012; 84:1198 Radiation Oncology Guidelines Version 3.0 RETURN 45 P age

46 RO-10.1 General Considerations RADIATION ONCOLOGY GUIDELINES RO-10~GYNECOLOGICAL CANCER (Vaginal, Vulvar, Uterine, Cervical) This disease group includes endometrial/uterine, cervical, vaginal and vulvar cancers. Management considerations with radiotherapy are complex, owing to the variety of applicable radiotherapy modalities and treatment indications. RO-10.2 Endometrial Cancer Almost all cases of endometrial cancer requiring radiotherapy are in the adjuvant setting following curative surgery (see American Brachytherapy Society Guidelines). Recommendations for adjuvant radiotherapy are based on the stage of disease and the absence or presence of adverse pathologic features. Adverse pathologic features indicating adjuvant treatment include the following: o grade 2 or 3 disease o myometrial invasion > 50% o age > 60 years o lymphovascular (LVSI) invasion o large tumor size (> 4 cm) o lower uterine segment (cervical) involvement Low risk patients (those patients who have none of the above features, i.e. grade 1 or 2 with less than 50% myometrial invasion) should not receive adjuvant radiotherapy due to demonstrated minimal risk of recurrence versus surgery alone (see ASTRO Choosing Wisely #6). For all other early stage disease, EBRT or vaginal cylinder brachytherapy (typically HDR) alone appear to offer equivalent disease control outcomes. Unusual histologies of endometrial malignancy include papillary serous adenocarcinoma, clear cell adenocarcinoma, endometrial stromal sarcoma, undifferentiated sarcoma and leiomyosarcoma), carcinosarcomas and malignant mixed mesodermal tumors. These tumors tend to be of higher grade and behave more aggressively than the more common endometrioid carcinomas. Post-operative radiotherapy is almost always indicated. Uncommon medically inoperable cases may be treated with pelvic EBRT followed by HDR or LDR boost therapy. Radiation Oncology Guidelines Version 3.0 RETURN 46 P age

47 RO-10.2 Endometrial Cancer CRT or IMRT Up to 28 fractions allowed in the adjuvant setting. Up to 35 fractions allowed in the definitive setting if brachytherapy cannot be performed LDR or HDR Up to 5 HDR fractions or 1 LDR fraction allowed when used as a monotherapy in the adjuvant setting. Up to 3 HDR fractions or 1 LDR fraction allowed when combined with EBRT in the adjuvant setting. Up to 5 HDR fractions or 1 LDR fraction allowed when combined with EBRT in the definitive setting. RO-10.3 Cervix Cancer Postoperative radiotherapy may be considered for patients undergoing surgery as primary treatment. In these instances, pelvic EBRT should be delivered to a dose of Gy. Postoperative EBRT is indicated in patients with the following adverse pathology. locoregional recurrence risk scenarios: o 2 or more of the following risk factors (if negative margins and lymph nodes): lymphovascular invasion, > 1/3 cervical stoma invasion, or tumor > 4 cm, or o Any one of the following risk factors: lymph node positivity or positive margin. For cases considered for definitive radiotherapy, combined EBRT and brachytherapy (typically multiple fractions of tandem and ovoid HDR) represents the standard of care (see American Brachytherapy Society Guidelines). IMRT should not be used to deliver high dose treatment to the cervix as replacement for brachytherapy, as this has resulted in inferior outcomes. When clinically indicated for treatment, para-aortic fields should be treated concurrently with pelvic nodes using IMRT to minimize toxicity. CRT or IMRT Up to 28 fractions allowed in the adjuvant setting or definitive setting with planned brachytherapy boost. Up to 39 fractions allowed in the definitive setting when brachytherapy cannot be delivered. LDR or HDR LDR boost as part of definitive treatment may be given using up to 2 implants. HDR boost as part of definitive treatment may be given in a maximum of 5 fractions. Up to 5 HDR fractions or 1 LDR fraction allowed when used as monotherapy adjuvantly. Up to 3 HDR fractions or 1 LDR fraction allowed when combined with EBRT adjuvantly. Radiation Oncology Guidelines Version 3.0 RETURN 47 P age

48 RO-10.4 Vaginal Cancer Primary radiotherapy consists of external beam radiotherapy with or without brachytherapy boost. EBRT dose is typically Gy with a brachytherapy boost or Gy if EBRT is used alone. Brachytherapy alone may be considered for patients with early stage disease characteristics as follows: o < 2 cm tumor size o well differentiated pathology o < 0.5 cm tumor thickness, o well defined lesion borders o no involvement of the rectovaginal septum CRT or IMRT Up to 28 fractions allowed in the adjuvant setting or definitive setting with planned brachytherapy boost. Up to 39 fractions allowed in the definitive setting when boost brachytherapy cannot be delivered. LDR or HDR Up to 3 HDR fractions and 1 LDR fraction allowed after pelvic EBRT. Up to 5 HDR fractions and 2 LDR fractions allowed if brachytherapy is used as a monotherapy. RO-10.5 Vulvar Cancer CRT or IMRT can be used in the treatment of vulvar cancer. Following definitive surgery, it is customary to deliver a postoperative dose of Gy to the pelvis with a boost dose to 60 Gy delivered to the inguinal bed when positive disease or extracapsular extension is noted at surgery. When the patient is being treated definitively with chemoradiation, boost to gross disease of up to 70 Gy with EBRT is allowed. Brachytherapy is not generally indicated in the management of vulvar cancer. References Cervical Cancer. In: Clinical Radiation Oncology 2 nd Ed Handbook of Evidence-Based Radiation Oncology. 2nd Ed 4. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Endometrial Cancers 5. Handbook of Evidence-Based Radiation Oncology. 2nd Ed. 6. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Endometrial Cancers 7. Lancet Mar 6; 375(9717): Radiation Oncology Guidelines Version 3.0 RETURN 48 P age

49 8. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Endometrial Cancers 9. Int J Radiat Oncol Biol Phys Apr 1; 82(5): Int J Radiat Oncol Biol Phys Jul 1; 53(3): Rev Assoc Med Bras Jul-Aug; 57(4): Gynecol Oncol. 2004; 92: Ann Oncol. 2007; 18(10): Lancet Mar 6; 375(9717): J Clin Oncol Apr 1; 22(7): Gynecol Oncol Mar; 92(3): Clinical Radiation Oncology. 3 rd Ed 2012, Chapter Principles and Practice of Radiation Oncology. 3 rd Ed. 1998, Chapter Handbook of Evidence-Based Radiation Oncology. 2nd Ed. 20. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Endometrial Cancers 21. Clinical Radiation Oncology. 3 rd Ed 2012, Chapter Principles and Practice of Radiation Oncology. 3 rd Ed. 1998, Chapter Int J Gynecol Cancer Nov; 21(8): National Comprehensive 25. Cancer Network. Clinical Practice Guidelines in Oncology: Endometrial Cancers 26. Clinical Radiation Oncology. 3 rd Ed 2012, Chapter Eur J Cancer Apr; 44(6): Eur J Surg Oncol May; 31(4): Curr Opin Oncol Jul; 16(4): Cervical Cancer. In: Clinical Radiation Oncology 2 nd Ed pp Principles and Practice of Radiation Oncology. 3 rd Ed. 1998, Chapter Handbook of Evidence-Based Radiation Oncology. 2 nd Ed. 33. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Cervical Cancers 34. Vaginal Cancer. In: Clinical Radiation Oncology 2 nd Ed Principles and Practice of Radiation Oncology. 3 rd Ed Handbook of Evidence-Based Radiation Oncology. 2nd Ed. 37. Int J Radiat Oncol Biol Phys May 1; 62(1): Int J Radiat Oncol Biol Phys. 1992; 24(4): J Obstet Gynaecol Can ;35(4): American Brachytherapy Society. Radiation Oncology Guidelines Version 3.0 RETURN 49 P age

50 RADIATION ONCOLOGY GUIDELINES RO-11~SARCOMA RO-11.0 General Considerations Surgery is the primary treatment modality for sarcoma, however a multidisciplinary approach is generally recommended to facilitate anatomic and functional preservation. Treatment for resectable disease may include neoadjuvant, IORT and/or adjuvant radiation therapy. All resected tumors with close or positive surgical margins should be considered for adjuvant radiation therapy due to high risk of local recurrence. Unresectable or medically inoperable sarcomas may be considered for definitive radiation therapy. Borderline resectable disease may be rendered technically resectable following a course of neoadjuvant radiotherapy. Primary treatment for gastrointestinal stromal tumors (GISTs) is surgery +/- systemic therapy. Radiation therapy is not indicated in the adjuvant setting and is generally reserved for palliation of drug-resistant disease. RO-11.1 Soft Tissue Sarcoma Preoperative treatment is indicated for patients presenting with selected tumors with high likelihood of close or positive surgical margins in order to facilitate subsequent complete resection. Commonly, a dose of Gy is prescribed in the neoadjuvant setting. Intraoperative and postoperative treatment is indicated for patients following surgery of deep compartment tumors and selected large superficial compartment tumors. Intraoperative and/or postoperative radiotherapy using external beam therapy, IORT or brachytherapy may be necessary for cases with close or positive margins following neoadjuvant therapy and attempted resection. If surgical margins are positive, then boost doses up to 70 Gy are appropriate. Patients deemed unresectable following preoperative therapy may require radiation dose escalation to Gy. Typically CRT is considered sufficient, but IMRT may also be considered appropriate for this disease group. CRT or IMRT Up to 35 fractions is allowed in the adjuvant setting with negative margins. Up to 39 fractions is allowed in the adjuvant setting with positive margins. Up to 42 fractions is allowed in the definitive setting for medically or technically inoperable disease. Up to 28 fractions is allowed in the neoadjuvant setting. Radiation Oncology Guidelines Version 3.0 RETURN 50 P age

51 RO-11.2 Sarcoma of Bone These uncommon malignancies can often be treated using CRT. o For Ewing s sarcoma, a dose of 45 Gy in 25 fractions followed by a boost dose to Gy is commonly used. o For chondrosarcoma, a dose of 45 Gy in 25 fractions followed by a boost dose to Gy is commonly used. o For osteosarcoma, a dose of 45 Gy in 25 fractions followed by a boost dose to Gy is commonly used. Radiation Oncology Guidelines Version 3.0 RETURN 51 P age

52 RADIATION ONCOLOGY GUIDELINES RO-12~RECTAL and ANAL CANCER Radiotherapy is used in the adjuvant and neoadjuvant settings for the management of rectal cancer. In the neoadjuvant setting, radiotherapy may allow for cytoreduction of tumor to permit sphincter-sparing surgery. In the adjuvant setting, radiotherapy addressed microscopic disease risk at the primary site and regional lymphatics. Tumors located below the peritoneal reflection and with T3N0 and greater pathologic stage are considered appropriate for adjuvant radiotherapy In almost all cases, EBRT is the sole radiotherapy modality used. Intraoperative radiotherapy boost may be necessary for treatment of selected cases following attempted resection with positive margins. Among EBRT modalities, CRT is considered most appropriate for rectal cancer therapy. Typically bowel displacement technique allows for adequate small bowel tissue sparing. Patients with a history of bowel surgery or inability to tolerate a displacement technique may benefit from IMRT use. Anal cancer of early stage may be treated with surgical resection alone. Advanced disease typically includes definitive chemoradiotherapy. CRT is typically utilized however patients with a history of bowel surgery or inability to tolerate a displacement technique may benefit from IMRT use. CRT or IMRT Up to 30 fractions is allowed in the neoadjuvant setting or adjuvant setting with negative surgical margins Up to 35 fractions is allowed in the adjuvant setting with positive surgical margins Up to 39 fractions is allowed in the definitive setting for unresectable disease Radiation Oncology Guidelines Version 3.0 RETURN 52 P age

53 RADIATION ONCOLOGY GUIDELINE REFERENCES RO-1~CENTRAL NERVOUS SYSTEM RO-1.1 Conditions not Associated with Tumors Han JH, Kim DG, Chung HT, et al. Long-term outcome of gamma knife radiosurgery for treatment of typical trigeminal neuralgia. Int J Radiat Oncol Biol Phys 2009 Nov 1; 75(3): RO-1.2 Benign Brain Tumors (including Pituitary) Pollock BE, Foote RL, Link MJ, et al. Repeat radiosurgery for idiopathic trigeminal neuralgia. Int J Radiat Oncol Biol Phys 2005 Jan 1;61(1): Fuss M, Debus J, Lohr F, et al. Conventionally fractionated stereotactic radiotherapy (FSRT) for acoustic neuromas. Int J Radiat Oncol Biol Phys 2000;48: RO-1.3 Malignant or High Grade Tumors Schroeder TM, Chintagumpala M, Okcu MF, et al. Intensity-modulated radiation therapy in childhood ependymoma. Int J Radiat Oncol Biol Phys 2008 July 15; 71(4): Halperin EC. Impact of radiation technique upon the outcome of treatment for medulloblastoma. Int J Radiat Oncol Biol Phys 1996;36: Tsao MN, Mehta MP, Whelan TJ, et al. The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for malignant glioma. Int J Radiat Oncol Biol Phys 2005;63: Hochberg FH and Pruitt A. Assumptions in the radiotherapy of glioblastoma. Neurology 1980 Sept. 1;30(9): Souhami L, Seiferheld W, Brachman D, et al. Randomized comparison of stereotactic radiosurgery followed by conventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastoma multiforme: report of Radiation Therapy Oncology Group protocol. Int J Radiat Oncol Biol Phys 2004;60: RO-1.4 Metastatic Disease Videtic GM, Gaspar LE, Aref AM, et al. American College of Radiology appropriateness criteria on multiple brain metastases. Int J Radiat Oncol Biol Phys 2009;75: Koyfman SA, Tendulkar RD, Chao ST, et al. Stereotactic radiosurgery for single brainstem metastases: the Cleveland Clinic experience. Int J Radiat Oncol Biol Phys 2010 Oct. 1;78(2): Chang EL, Wefel JS, Hess KR, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncology 2009 Nov;10(11): Andrews DW, Scott CB, Sperduto PW, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet 2004 May 22;363(9422): Gaspar LE, Scott C, Murray K, et al. Validation of the RTOG recursive partitioning analysis (RPA) classification for brain metastases. Int J Radiat Oncol Biol Phys 2000;47: RO-2~BREAST CANCER RO-2.1 External Beam Therapy Vikram B, Coleman CN, Deye JA. Current status and future potential of advanced technologies in radiation oncology. Part 2. State of the science by anatomic site. Oncology 2009 April 15;23(4): RO-2.2 Brachytherapy Dirbas FM. Accelerated partial breast irradiation: where do we stand? J Natl Compr Canc Netw 2009 April 15;23(4): Consensus statement: APBI from ASTRO. Int J Radiat Oncol Biol Phys 2009;74: Keisch M, Arthur D, Patel R, et al. American Brachytherapy Society Breast Brachytherapy Task Group. February 2007, Accessed January 28, Radiation Oncology Guidelines Version 3.0 RETURN 53 P age

54 RADIATION ONCOLOGY GUIDELINE REFERENCES RO-3~LUNG AND OTHER THORACIC CANCERS RO-3.0 General Considerations Ettinger DS, Akerley W, Belpler G, et al. Non-small cell lung cancer: clinical practice guidelines in oncology. J Natl Compr Canc Netw 2010 July;8(7): RO-3.1 Small Cell Lung Cancer (SCLC) Paumier A and Le Pechoux C. Radiotherapy in small-cell lung cancer: where should it go? Lung Cancer 2010 Aug;69(2): Zhu H, Zhou Z, Ou G, et al. Thoracic radiation therapy (TRT) improved overall survival for patients with extensive stage small cell lung cancer. Abstract 2712 presented at 52 nd ASTRO Annual Meeting. October 31-November 4, 2010;San Diego, California. RO-3.2 Non-Small Cell Lung Cancer (NSCLC) Timmerman RD, Paulus R, Galvin J, et al. Stereotactic body radiation therapy for medically inoperable early-stage lung cancer patients: analysis of RTOG Int J Radiat Oncol Biol Phys 2009;75(3suppl):S3. SBRT for Lung Cancer: report of the ASTRO Emerging Technology Committee (ETC). January 1, 2010, Accessed February 1, Bradley JD, Moughan J, Graham MV, et al. A phase I/II radiation dose escalation study with concurrent chemotherapy for patients with inoperable stages I to III non-small cell lung cancer: phase I results of RTOG Int J Radiat Oncol Biol Phys Jun 1;77(2): Nakayama H, Satoh H, Kurishima K, et al. High-dose conformal radiotherapy for patients with stage III non-small-cell lung carcinoma. Int J Radiat Oncol Biol Phys 2010 Nov 1;78(3): Ramella S, Trodella L, Mineo TC, et al. Adding ipsilateral V20 and V30 to conventional dosimetric constraints predicts radiation pneumonitis in stage IIIA-B NSCLC treated with combined-modality therapy. Int J Radiat Oncol Biol Phys Jan 1;76(1): Videtic GM, Stephans K, Reddy C, et al. Intensity-modulated radiotherapy-based stereotactic body radiotherapy for medically inoperable early-stage lung cancer: excellent local control. Int J Radiat Oncol Biol Phys Jun 1;77(2): ASTRO stereotactic body radiation therapy (SBRT) model coverage policy. August 2, 2010, Accessed February 1, Ettinger DS, Akerley W, Belpler G, et al. Non-small cell lung cancer: clinical practice guidelines in oncology. J Natl Compr Canc Netw 2010 July;8(7): RO-4~LYMPHOMA Engert A, Diehl V, et al. Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin s lymphoma.: 10 years of follow-up of the GHSG HD9 study. J Clin Oncol 2009 Sept 20;27(27): Yahalom J, Varsos G, Fuks Z, et al. Adjuvant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy after radiation therapy in stage I low-grade and intermediate-grade non- Hodgkin lymphoma. Results of a prospective randomized study. Cancer 1993 Apr 1;71(7): o Meyer RM, Gospodarowicz MK, Connors JM, et al. Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin s lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group. J Clin Oncol 2005;23: Aleman BMP, Raemaekers JMM, Tirelli U, et al. Involved-field radiotherapy for advanced Hodgkin s Lymphoma. N Engl J Med 2003;348: Engert A, Plütschow A, Eich HT, et al. Reduced treatment intensity in patients with early-stage Hodgkin s Lymphoma. N Engl J Med 2010;363: Radiation Oncology Guidelines Version 3.0 RETURN 54 P age

55 Girinsky T, van der Maazen R, Specht L, et al. involved-node radiotherapy (INRT) in patients with early Hodgkin lymphoma: concepts and guidelines. Radiother Oncol 2006 June;79(3): RO-5~BONE METASTASIS RO-5.2 Radiation Therapy Techniques Lutz S, Berk L, Chang E, et al. Palliative radiotherapy for bone metastases: an ASTRO evidence-based guideline. (In print). Accessed February 1, Fairchild A, Barnes E, Ghosh S, et al. International patterns of practice in palliative radiotherapy for painful bone metastases: evidence-based practice? Int J Radiat Oncol Biol Phys 2009 Dec 1;75(5): Roberts CC, Daffner RH, Weissman BN, et al. ACR appropriateness criteria on metastatic bone disease. J Am Coll Radiol 2010 June;7(6): RO-6~ CANCERS of the UPPER GASTROINTESTINAL SYSTEM RO-6.1 Primary Hepatic Tumors Benson AB, Abrams TA, Ben-Josef E, et al. Hepatobiliary cancers. J Natl Compr Canc Netw 2009;7: RO-6.2 Gastric (Stomach) Cancer Callister MD and Gunderson LL. Advancements in radiation techniques for gastric cancer. J Natl Compr Canc Netw 2010;8(4): RO-6.3 Pancreatic and Extra-Hepatic Biliary Tumors Ghafoori AP, Nelson JW, Willett CG, et al. Radiotherapy in the treatment of patients with unresectable extrahepatic cholangiocarcinoma. Int J Radiat Oncol Biol Phys 2010 Sep 22 Abstract. RO-6.4 Treatment of Metastatic Disease in the Upper Abdomen and Liver Engstrom PF, Arnoletti JP, Benson AB, et al. Colon cancer. J Natl Compr Canc Netw 2009;7: ASTRO stereotactic body radiation therapy (SBRT) model coverage policy. August 2, 2010, SBRTMP.pdf. Accessed February 1, RO-7~PROSTATE CANCER RO-7.0 General Considerations Shao YH, Albertsen PC, Roberts CB, et al. Risk profiles and treatment patterns among men diagnosed as having prostate cancer and a prostate-specific antigen level below 4.0 ng/ml. Arch Intern Med 2010 July 26;170(14): RO-7.1 External Beam Therapy Buyyounouski MK, Price RA Jr, Harris EE, et al. Stereotactic body radiotherapy for primary management of early-stage, low- to intermediate-risk prostate cancer: report of the American Society for Therapeutic Radiology and Oncology Emerging Technology Committee. Int J Radiat Oncol Biol Phys 2010 Apr;76(5): Michalski JM, Lawton C, El Naqa I, et al. Development of RTOG consensus guidelines for the definition of the clinical target volume for postoperative conformal radiation therapy for prostate cancer. Int J Radiat Oncol Biol Phys Feb 1;76(2): Stephenson AJ, Scardino PT, Kattan MW, et al. Predicting the outcome of slvage radiation therapy for recurrent prostate cancer after definitive prostatectomy. J Clin Oncol 2007 May 20;25(15): Trock BJ, Han M, Freedland SJ, et al. Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after definitive prostatectomy. JAMA 2008;299(23): Thompson IM Jr, Tangen CM, Paradelo J, et al. Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA 2006 Nov 15;296(19): Radiation Oncology Guidelines Version 3.0 RETURN 55 P age

56 Thompson IM, Tangen CM, Paradelo J, et al. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial. J Urol 2009 March;181(3): Bernard JR Jr, Buskirk SJ, Heckman MG, et al. Salvage radiotherapy for rising prostate-specific antigen levels after definitive prostatectomy for prostate cancer: dose-response analysis. Int J Radiat Oncol Biol Phys 2010 March 1:76(3): Cooperberg MR, Moul JW, Carroll PR. The changing face of prostate cancer. J Clin Oncol 2005 Nov 10;23(32): American Urological Association Prostate Cancer: guideline for the management of clinically localized prostate cancer: 2007 update. guidelines-and-quality-care/clinicalguidelines/main-reports/proscan07/content.pdf. Accessed February 2, RO-7.2 Brachytherapy Merrick GS, Zelefsky MJ, Sylvester J, et al. American Brachytherapy Society Prostate Low-Dose Rate Task Group. Not dated. Accessed February 2, Hsu IC, Yamada Y, Vigneault E, et al. American Brachytherapy Society Prostate High-Dose Rate Task Group. August 2008, Accessed February 2, Taira AV, Merrick GS, Galbreath RW, et al. Natural history of clinically staged low- and intermediaterisk prostate cancer treated with monotherapeutic permanent interstitial brachytherapy. Int J Radiat Oncol Biol Phys 2010 Feb 1;76(2): Taira AV, Merrick GS, Butler WM, et al. Long-term outcome for clinically localized prostate cancer treated with permanent interstitial brachytherapy. Int J Radiat Oncol Biol Phys 2010 Jun 2 (e-pub ahead of print). doi: /j.ijrobp RO-10~HEAD and NECK CANCER Dirix P, Nuyts S. Evidence-based organ-sparing radiotherapy in head and neck cancer. Lancet Oncol 2010; 11: Clark CH et al. Pre-trial quality assurance processes for an intensity-modulated radiation therapy (IMRT) trial: PARSPORT, a UK multicentre Phase III trial comparing conventional radiotherapy and parotidsparing IMRT for locally advanced head and neck cancer. Br J Radiol 2009; 82: Pfister DG et al. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Head and neck cancers. J Natl Compr Canc Netw 2011; 9: Bhide SA, Nutting CM. Advances in radiotherapy for head and neck cancer. Oral Oncol 2010; 46: Bourhis J et al. Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an openlabel phase 3 randomised trial. Lancet Oncol 2012; 13: Chan AT, Gregoire V, Lefebvre JL, Licitra L, Felip E. Nasopharyngeal cancer: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21 Suppl 5:v187-9.: v187-v189. Chen L et al. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial. Lancet Oncol 2012; 13: Chen QY et al. Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: phase III randomized trial. J Natl Cancer Inst 2011; 103: Corvo R. Evidence-based radiation oncology in head and neck squamous cell carcinoma. Radiother Oncol 2007; 85: Daly-Schveitzer N, Julieron M, Tao YG, Moussier A, Bourhis J. Intensity-modulated radiation therapy (IMRT): toward a new standard for radiation therapy of head and neck cancer? Eur Ann Otorhinolaryngol Head Neck Dis 2011; 128: Radiation Oncology Guidelines Version 3.0 RETURN 56 P age

57 Erickson BA et al. American Society for Radiation Oncology (ASTRO) and American College of Radiology (ACR) practice guideline for the performance of high-dose-rate brachytherapy. Int J Radiat Oncol Biol Phys 2011; 79: Gregoire V, Lefebvre JL, Licitra L, Felip E. Squamous cell carcinoma of the head and neck: EHNS- ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21 Suppl 5:v184-6.: v184-v186. Hall SF, Groome PA, Irish J, O'Sullivan B. Radiotherapy or surgery for head and neck squamous cell cancer: establishing the baseline for hypopharyngeal carcinoma? Cancer 2009; 115: Mallick I, Waldron JN. Radiation therapy for head and neck cancers. Semin Oncol Nurs 2009; 25: Mazeron JJ et al. GEC-ESTRO recommendations for brachytherapy for head and neck squamous cell carcinomas. Radiother Oncol 2009; 91: McDonald MW et al. ACR appropriateness criteria retreatment of recurrent head and neck cancer after prior definitive radiation expert panel on radiation oncology-head and neck cancer. Int J Radiat Oncol Biol Phys 2011; 80: Mesia NR, Pastor BM, Cruz Hernandez JJ, Isla CD. SEOM clinical guidelines for the treatment of head and neck cancer. Clin Transl Oncol 2010; 12: NCCN Clinical Practice Guidelines in Oncology: Head and Neck Cancers ( - Version NCCN.org Nutting CM et al. Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial. Lancet Oncol 2011; 12: Salama JK et al. ACR appropriateness criteria(r) adjuvant therapy for resected squamous cell carcinoma of the head and neck. Oral Oncol 2011; 47: Shibuya H. Current status and perspectives of brachytherapy for head and neck cancer. Int J Clin Oncol 2009; 14: 2-6. Thariat J et al. New techniques in radiation therapy for head and neck cancer: IMRT, CyberKnife, protons, and carbon ions. Improved effectiveness and safety? Impact on survival? Anticancer Drugs 2011; 22: Zackrisson B et al. Two-year results from a Swedish study on conventional versus accelerated radiotherapy in head and neck squamous cell carcinoma--the ARTSCAN study. Radiother Oncol 2011; 100: RO-11~GYNECOLOGICAL CANCER RO-11.1 Ovarian Cancer Koh W, Moore DH, Ovarian Cancer. In: Gunderson LL, Tepper JE, et al., editors. Clinical Radiation Oncology 2 nd Ed. Philadelphia: Churchill Livingstone; National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Ovarian Cancers Available at: PDF/ovary.pdf. Accessed on June2012. CA, Brady LW, Principles and Practice of Radiation Oncology. 3 rd Ed. 1998, Philadelphia, PA. EK, Roach III M, Handbook of Evidence-Based Radiation Oncology. 2 nd Ed. Levanon K, Crum C, Drapkin R. New insights into the pathogenesis of serous ovarian cancer and its clinical impact. J Clin Oncol Nov 10; 26(32): Epub 2008 Oct 14. Chiara S, Conte P, Franzone P, Orsatti M, Bruzzone M, Rubagotti A, Odicino F, Rugiati S, Carnino F, Rosso R, et al. High risk early-stage ovarian cancer. Randomized clinical trial comparing cisplatin plus cyclophasphamide versus whole abdominal radiotherapy. Am J Clin Oncol Feb; 17(1):72-6. Redman CW, Mould J, Warwick J, Rollason T, Luesley DM, Budden J, Lawton FG, Blackledge GR, Chan KK. The West Midlands epithelial ovarian cancer adjuvant therapy trial. Clin Oncol (R Coll Radiol). 1993;5(1):1-5. Sorbe B; Swedish-Norgewian Ovarian Cancer Study Group. Consolidation treatment of advanced (FIGO stage III) ovarian carcinoma in complete surgical remission after induction chemotherapy: a randomized, controlled, clinical trial comparing whole abdominal radiotherapy, chemotherapy, and no further treatment. Int J Gynecol Cancer May-Jun; 13(3): Radiation Oncology Guidelines Version 3.0 RETURN 57 P age

58 Lambert HE, Rustin GJ, Gregory WM, Nelstrop AE. A randomized trial comparing single-agent carboplatin with carboplatin followed by radiotherapy for advanced ovarian cancer: a North Thames Ovary Group study. J Clin Oncol Mar; 11(3): ovariancancer.jhmi.edu/treatment.cfm Trimble EL. Innovative therapies for advanced ovarian cancer. Semin Oncol 3:24-30, Gore M, Ten Bokkel Huinink W, Carmichael J, Gordon A, Davidson N, Coleman et al. Clinical evidence for topotecan-paclitaxel non-cross-resistance in ovarian cancer. J Clin Oncol 19(7): , Clarke-Pearson DL, Van Le L, Iveson T, Whitney CW, Hanjani P, et al. Oral topotecan as single agent second line chemotherapy in patients with advanced ovarian cancer. J Clin Oncol 19: , Vermorken JB. The integration of paclitaxel and new platinum compounds in the treatment of advanced ovarian cancer. J Gynecol Cancer 11:21-30, Rainczuk A, Rao J, Gathercole J, Stephens A. The emerging role of CXC chemokines in epithelial ovarian cancer. Reproduction Jul 6. Chambers SK, Martinez JD. The significance of p53 isoform expression in serous ovarian cancer. Future Oncol Jun; 8(6): Högberg T, Glimelius B, Nygren P; SBU-group. Swedish Council of Technology Assessment in Health Care. A systematic overview of chemotherapy effects in ovarian cancer. Acta Oncol. 2001; 40(2-3): Chase DM, Wenzel LB, Monk BJ. Quality-of-life results used to endorse changes in standard of care for recurrent platinum-sensitive ovarian cancer. Expert Rev Pharmacoecon Outcomes Res Jun; 12(3): Sourbier C. Ovarian cancer: emerging molecular-targeted therapies. Biologics. 2012; 6: Pub 2012 Jun 20. Du XL, Jiang T, Sheng XG, Li QS, Wang C, Yu H. PET/CT scanning guided intensity-modulated radiotherapy in treatment of recurrent ovarian cancer. Eur J Radiol Apr 20. Hoskins PJ, Le N, Gilks B, Tinker A, Santos J, Wong F, Swenerton KD. Low-stage ovarian clear cell carcinoma: population-based outcomes in British Columbia, Canada, with evidence for a survival benefit as a result of irradiation. J Clin Oncol May 10; 30(14): Epub 2012 Apr 9. Ingersoll SB, Ahmad S, Finkler NJ, Edwards JR, Holloway RW. Cellular Therapy for Ovarian Cancer: Experimental and Clinical Perspectives. Curr Med Chem Jun 7. Kroep JR, Nortier JW. The role of bevacizumab in advanced epithelial ovarian cancer. Curr Pharm Des May 14 RO-11.2 Endometrial Cancer Gunderson, LL and Tepper JE, Clinical Radiation Oncology. 3 rd Ed. 2012, Philadelphia, Pa.: London: Saunders, Chapter 45. Perez CA, Brady LW, Principles and Practice of Radiation Oncology. 3 rd Ed. 1998, Philadelphia, PA. Chapter 63. Umar A, Boland CR, Terdiman JP, et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 96: , Silverberg, S.G., Mullen, D., Faraci, J. et al. Endometrial Carcinoma: Clinical-Pathologic comparison of cases in postmenopausal women receiving and not receiving exogenous estrogen. Cancer 45:3018, ASTEC/EN.5 Study Group, Blake P, Swart AM, Orton J, Kitchener H, Whelan T, Lukka H, Eisenhauer E, Bacon M, Tu D, Parmar MK, Amos C, Murray C, Qian W. Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN. 5 randomised trials): pooled trial results, systematic review, and meta-analysis. Lancet 2009; 373: Creasman WT, Mutch DE, Herzog TJ. Astec lymphadenectomy and radiation therapy studies: are conclusions valid? Gynecol Oncol Jan; 108(1): Epub 2007 Nov 9. Chino JP, Jones E, Berchuck A, Secord AA, Havrilesky LJ. The influence of radiation modality and lymph node dissection on survival in early-stage endometrial cancer. Lancet Jan10; 373(9658): Epub 2008 Dec 16. Hogberg T, Rosenberg P, Kristensen G, et al. a randomized phase III study on adjuvant treatment with radiation +/- chemotherapy in early staged high risk endometrial cancer (NSGO-EC -9501/EORTC 55991). J Clin Oncol.2007; 25(18S):5503. Radiation Oncology Guidelines Version 3.0 RETURN 58 P age

59 Susumu N, Sagae S, Udagawa Y, Niwa K, Kuramoto H, Satoh S, Kudo R; Japanese Gynecologic Oncology Group. Randomized phase III trial of pelvic radiotherapy versus cisplatin-based combined chemotherapy in patients with intermediate- high risk endometrial cancer: a Japanese Gynecologic Oncology Group study. Br J Cancer Aug 7; 95(3): Epub 2006 Jul 25. Lupe K, Kwon J, D Souza D, et al. Adjuvant paclitaxel and carboplatin chemotherapy with involved field radiation in advanced endometrial cancer: a sequential approach. Int J Radiat Oncol. Biol Phys. 2007; 67(1): Mahdavi A, Tajalli TR, Dalmar A, Vasilev SA, Lentz SE, Berman ML. Role of adjuvant chemotherapy in patients with early stage uterine papillary serous cancer. Int J Gynecol Cancer Nov; 21(8): Hansen EK, Roach III M, Handbook of Evidence-Based Radiation Oncology 2 nd Ed. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Endometrial Cancers Available at: PDF/endometrial.pdf. Accessed June2012. Maggi R, Lissoni A, Spina F, Melpignano M, Zola P, Favalli G, Colombo A, Fossati R. Adjuvant chemotherapy vs. radiotherapy in high-risk endometrial carcinoma: results of a randomized trial. Int J Radiat Oncol Biol Phys Apr 1; 82(5): Epub 2011 Jun 2. Alektiar KM, McKee A, Venkatraman E, McKee B, Zelefsky MJ, Mychalczak BR, Hoskins WJ, Barakat RR. Intravaginal high-dose-rate brachytherapy for Stage 1B (FIGO Grade 1, 2) endometrial cancer. Int J Radiat Oncol Biol Phys Jul 1; 53(3): Zuliani AC, Cairo AA, Esteves SC, Watanabe CC, Cunha Mde O, Souza GA. Adjuvant radiotherapy in early stage endometrial cancer. Rev Assoc Med Bras Jul-Aug; 57(4): Keys HM, Roberts JA, Brunetto VL, et al. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004; 92: Kong A, Simera I, Collingwood M, et al. Adjuvant radiotherapy for stage 1 endometrial cancer: systematic review and meta-analysis. Ann Oncol. 2007; 18(10): Nout RA, Putter H, Jurgenliemk-Schulz IM, et al. Vaginal brachytherapy versus external beam pelvic radiotherapy for high-intermediate risk endometrial cancer: results of the randomized PORTEC-2 trial. Lancet Mar 6; 375(9717): Creutzberg CL, van Putten WL, Wárlám-Rodenhuis CC, van den Bergh AC, de Winter KA, Koper PC, Lybeert ML, Slot A, Lutgens LC, Stenfert Kroese MC, Beerman H, van Lent M. Outcomes of high-risk stage 1C, grade 3, compared with stage 1 endometrial carcinoma patients: the Postoperative Radiation Therapy in Endometrial Carcinoma Trial. J Clin Oncol Apr 1; 22(7): Greven K, Winter K, Underhill K, Fontenesci J, Cooper J, Burke T. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol 2004 Mar; 92(3): Reed NS, Mangioni C, Malmström H, Scarfone G, Poveda A, Pecorelli S, Tateo S, Franchi M, Jobsen JJ, Coens C, Teodorovic I, Vergote I, Vermorken JB; European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group. Phase III randomized study to evaluate the role of adjuvant pelvic radiotherapy in the treatment of uterine sarcomas stages I and II: a European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study (protocol 55874) Eur J Cancer Apr; 44(6): Epub 2008 Apr 2. Benoit L, Arnould L, Cheynel N, Goui S, Collin F, Fraisse J, Cuisenier J. The role of surgery and treatment trends in uterine sarcoma. Eur J Surg Oncol May; 31(4): Giuntoli RL 2nd, Bristow RE. Uterine leimoyosarcoma: present management. Curr Opin Oncol Jul; 16(4): Randall ME, Filiaci VL, Muss H, Spirtos NM, Mannel RS, Fowler J, Thigpen JT, Benda JA; Gynecologic Oncology Group Study. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol Jan 1; 24(1): Epub 2005 Dec 5. RO-11.3 Cervix Cancer Koh W, Moore DH, Cervical Cancer. In: Gunderson LL, Tepper JE, et al., editors. Clinical Radiation Oncology 2 nd Ed. Philadelphia: Churchill Livingstone; Perez CA, Brady LW, Principles and Practice of Radiation Oncology. 3 rd Ed 1998, Philadelphia, PA. Chapter 62. Radiation Oncology Guidelines Version 3.0 RETURN 59 P age

60 Hansen EK, Roach III M, Handbook of Evidence-Based Radiation Oncology. 2 nd Ed. Detroit Free Press, A Gannett Company/Life; June 24, Small W Jr, Mell LK, Anderson P, Creutzberg C, De Los Santos J, Gaffney D, Jhingran A, Portelance L, Schefter. Consensus guidelines for delineation of clinical target volume for intensity-modulated pelvic radiotherapy in postoperative treatment of endometrial and cervical cancer. Int J Radiat Oncol Biol Phys Jun 1; 71(2): Epub 2007 Nov 26. Nag S, Cardenes H, Chang S, Das IJ, Erickson B, Ibbott GS, Lowenstein J, Roll J, Thomadsen B, Varia M; Image-Guided Brachytherapy Working Group. Proposed guidelines for image-based intracavitary brachytherapy for cervical carcinoma: report from Image-Guided Brachytherapy Working Group. Int J Radiat Oncol Biol Phys Nov 15; 60(4): Viswanathan AN, Thomadsen B; American Brachytherapy Society Cervical Cancer Recommendations Committee; American Brachytherapy Society. American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part I: general principles. Brachytherapy Jan-Feb; 11(1): Viswanathan AN, Beriwal S, De Los Santos JF, Demanes DJ, Gaffney D, Hansen J, Jones E, Kirisits C, Thomadsen B, Erickson B; American Brachytherapy Society. American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part II: high dose rate brachytherapy. Brachytherapy Jan-Feb; 11(1): Lee LJ, Das IJ, Higgins SA, Jhingran A, Small W Jr, Thomadsen B, Viswanathan AN, Wolfson A, Eifel P; American Brachytherapy Society. American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part III: low dose rate and pulsed dose rate brachytherapy. Brachytherapy Jan-Feb; 11(1):53-7. Sedlis A, Bundy BN, Rotman MZ, Lentz SS, Muderspach LI, Zaino RJ. A randomized trial of pelvic radiation therapy versus no further therapy in selected patients with stage IB carcinoma of the cervix after definitive hysterectomy and pelvic lymphadenectomy: A Gynecologic Oncology Group Study.Gynecol Oncol May; 73(2): Wang N, Guan QL, Wang K, Zhou X, Gao C, Yang HT, Ni TG. Radiochemotherapy versus radiotherapy in locally advanced cervical cancer: a meta-analysis. Arch Gynecol Obstet Jan; 283(1): Epub 2010 Feb 16. Eifel PJ, Winter K, Morris M, Levenback C, Grigsby PW, Cooper J, Rotman M, Gershenson D, Mutch DG. Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for highrisk cervical cancer: and update of radiation therapy oncology group trial (RTOG) J Clin Oncol Mar 1; 22(5): Pearcey R, Brundage M, Drouin P, Jeffrey J, Johnston D, Lukka H, MacLean G, Souhami L, Stuart G, Tu D. Phase III trial comparing definitive radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol Feb 15; 20(4): Peters WA 3rd, Liu PY, Barrett RJ 2nd, Stock RJ, Monk BJ, Berek JS, Souhami L, Grigsby P, Gordon W Jr, Alberts DS. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after surgery in high-risk early-stage cancer of the cervix. J Clin Oncol Apr; 18(8): Monk BJ, Wang J, Im S, Stock RJ, Peters WA 3rd, Liu PY, Barrett RJ 2nd, Berek JS, Souhami L, Grigsby PW, Gordon W Jr, Alberts DS; Gynecologic Oncology Group; Southwest Oncology Group; Radiation Therapy Oncology. Rethinking the use of radiation and chemotherapy after definitive hysterectomy: a clinical-pathologic analysis of a Gynecologic Oncology Group/Southwest Oncology Group/Radiation Therapy Oncology Group trial. Gynecol Oncol Mar; 96(3): Rotman M, Sedlis A, Piedmonte MR, Bundy B, Lentz SS, Muderspach LI, Zaino RJ. A phase III randomized trial of post operative pelvic irradiation in Stage IB cervical carcinoma with poor prognostic features: follow-up of a gynecologic oncology group study. Int J Radiat Oncol Biol Phys May 1; 65(1): Epub 2006 Jan 19. Lee KB, Lee JM, Ki KD, Lee SK, Park CY, Ha SY. Comparison of adjuvant chemotherapy and radiation in patients with intermediate risk factors after definitive surgery in FIGO stage IB-IIA cervical cancer. Int J Gynecol Cancer Sep-Oct;18(5): Epub 2007 Nov 16. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Cervical Cancers. Available at: PDF/cervical.pdf. Accessed on June2012. Radiation Oncology Guidelines Version 3.0 RETURN 60 P age

61 Swift PS, Hsu IC. Cancer of the Uterine Cervix. In: Leibel SA, Phillips TL, editors. Textbook of Radiation Oncology 2 nd Ed. Philadelphia: Saunders; pp RO-11.4 Vaginal Cancer Koh W, Moore DH, Vaginal Cancer. In: Gunderson LL, Tepper JE, et al., editors. Clinical Radiation Oncology 2 nd Ed. Philadelphia: Churchill Livingstone; Perez CA, Brady LW, Principles and Practice of Radiation Oncology. 3 rd Ed 1998, Philadelphia, PA. Hansen EK, Roach III M, Handbook of Evidence-Based Radiation Oncology. 2 nd Ed. Detroit Free Press, A Gannett Company/Life; June 24, Plentl AA, Friedman EA. Lymphatic system of the female genitalia. The morphologic basis of oncologic diagnosis and therapy. Major Probl Obstet Gynecol. 1971; 2: Choo YC, Anderson DG. Neoplasms of the vagina following cervical cancer. Gynecol Oncol Aug; 14(1): Sinha B, Stehman F, Schilder J, Clark L, Cardenes H. Indiana University experience in the management of vaginal cancer. Int J Gynecol Cancer May; 19(4): Frank SJ, Jhingran A, Levenback C, Eifel PJ. Definitive radiation therapy for squamous cell carcinoma of the vagina. Int J Radiat Oncol Biol Phys May 1; 62(1): Stock RG, Mychalczak B, Armstrong JG, Curtin JP, Harrison LB. The importance of brachytherapy technique in the management of primary carcinoma of the vagina. Int J Radiat Oncol Biol Phys. 1992; 24(4): Samant R, Lau B, E C, Le T, Tam T. Primary vaginal cancer treated with concurrent chemoradiation using Cis-platinum. Int J Radiat Oncol Biol Phys Nov 1; 69(3): Epub 2007 May 18. Micheletti L, Levi AC, Bogliatto F, Preti M, Massobrio M. Rationale and definition of the lateral extension of the inguinal lymphadenectomy for vulvar cancer derived from an embryological and anatomical study. J Surg Oncol Sep; 81(1): Wood WG, Giustini FG, Sohn S, Aranda RR. Verrucous carcinoma of the vagina. South Med J Apr; 71(4): Taylor MB, Dugar N, Davidson SE, Carrington BM. Magnetic resonance imaging of primary vaginal carcinoma. Clin Radiol Jun;62(6): Epub 2007 Apr 6. National Cancer Institute. Vaginal Cancer (PDQ):Treatment. Available at: Huh WK, Straughn JM Jr., Mariani A, et al. Salvage of isolated vaginal recurrences in women with surgical stage I endometrial cancer; a multiinstitutional experience. Int J Gynecol Cancer 2007; 17(4): Lian J, Dundas G, Carlone M, Ghosh S, Pearcey R. Twenty year review of radiotherapy for vaginal cancer: an institutional experience. Gynecol Oncol 2008; 111(2): Tran PT, Su Z, Lee P, et al. Prognostic factors for outcomes and complications for primary squamous cell carcinomas of the vagina treated with radiation. Int J Radiat Oncol Biol Phys 2006:S66:1052. RO-11.5 Vulvar Cancer Koh W, Moore DH, Vulvar Cancer. In: Gunderson LL, Tepper JE, et al., editors. Clinical Radiation Oncology 2 nd Ed. Philadelphia: Churchill Livingstone; Perez CA, Brady LW, Principles and Practice of Radiation Oncology. 3 rd Ed 1998, Philadelphia, PA. Hansen EK, Roach III M, Handbook of Evidence-Based Radiation Oncology. 2 nd Ed. Detroit Free Press, A Gannett Company/Life; June 24, RO-12~SARCOMA Gunderson LL and Tepper JE, Clinical Radiation Oncology. 3 rd Ed. 2012, Philadelphia, Pa.: London: Saunders. xvii, p Siegel R., D. Naishadham, and A. Jemal, Cancer Statistics, CA: A cancer journal for clinicians, (1): p O'Sullivan B., et al., Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet, (9325): p O'Sullivan B., et al., Preoperative radiotherapy for adult head and neck soft tissue sarcoma: assessment of wound complication rates and cancer outcome in a prospective series. World Journal of Surgery, (7): p Radiation Oncology Guidelines Version 3.0 RETURN 61 P age

62 Sadoski C., et al., Preoperative radiation, surgical margins, and local control of extremity sarcomas of soft tissues. Journal of Surgical Oncology, (4): p Tran Q.N., et al., Clinical outcomes of intraoperative radiation therapy for extremity sarcomas. Sarcoma, (1): p Sindelar W.F., et al., Intraoperative radiotherapy in retroperitoneal sarcomas. Final results of a prospective, randomized, clinical trial. Archives of Surgery, (4): p Pohar S., et al., Adjuvant high-dose-rate and low-dose-rate brachytherapy with external beam radiation in soft tissue sarcoma: a comparison of outcomes. Brachytherapy, (1): p Petersen, I.A., et al., Use of intraoperative electron beam radiotherapy in the management of retroperitoneal soft tissue sarcomas. Int J Radiat Oncol Biol Phys, (2): p Nag S., et al., The American Brachytherapy Society recommendations for brachytherapy of soft tissue sarcomas. Int J Radiat Oncol Biol Phys, (4): p Gieschen H.L., et al., Long-term results of intraoperative electron beam radiotherapy for primary and recurrent retroperitoneal soft tissue sarcoma. Int J Radiat Oncol Biol Phys, (1): p Pisters P.W., et al., Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol: official journal of the American Society of Clinical Oncology, (3): p Leibel S.A., et al., Intensity-modulated radiotherapy. Cancer, (2): p DeLaney T.F., et al., Advanced-technology radiation therapy in the management of bone and soft tissue sarcomas. Cancer control: Journal of the Moffitt Cancer Center, (1): p Alektiar K.M., M.F. Brennan, and S. Singer, Local control comparison of adjuvant brachytherapy to intensity-modulated radiotherapy in primary high-grade sarcoma of the extremity. Cancer, (14): p Alektiar K.M., et al., Impact of intensity-modulated radiation therapy on local control in primary softtissue sarcoma of the extremity. J Clin Oncol: official journal of the American Society of Clinical Oncology, (20): p Yang J.C., et al., Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol: official journal of the American Society of Clinical Oncology, (1): p Al-Absi E, et al., A systematic review and meta-analysis of oncologic outcomes of pre- versus postoperative radiation in localized resectable soft-tissue sarcoma. Annals of Surgical Oncology, (5): p Alektiar K.M., et al., Adjuvant radiation for stage II-B soft tissue sarcoma of the extremity. J Clin Oncol: official journal of the American Society of Clinical Oncology, (6): p Guadagnolo B.A., G.K. Zagars, and M.T. Ballo, Long-term outcomes for desmoid tumors treated with radiation therapy. Int J Radiat Oncol Biol Phys, (2): p Goy B.W., et al., The role of adjuvant radiotherapy in the treatment of resectable desmoid tumors. Int J Radiat Oncol Biol Phys, (3): p Ballo M.T., G.K. Zagars, and A. Pollack, Radiation therapy in the management of desmoid tumors Int J Radiat Oncol Biol Phys, (5): p Kepka L., et al., Results of radiation therapy for unresected soft-tissue sarcomas. Int J Radiat Oncol Biol Phys, (3): p Raney R.B., et al., Results of the Intergroup Rhabdomyosarcoma Study Group D9602 protocol, using vincristine and dactinomycin with or without cyclophosphamide and radiation therapy, for newly diagnosed patients with low-risk embryonal rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. J Clin Oncol: official journal of the American Society of Clinical Oncology, (10): p Arndt C.A., et al., Vincristine, actinomycin, and cyclophosphamide compared with vincristine, actinomycin, and cyclophosphamide alternating with vincristine, topotecan, and cyclophosphamide for intermediate-risk rhabdomyosarcoma: children's oncology group study D9803. J Clin Oncol: official journal of the American Society of Clinical Oncology, (31): p Pratt C.B., et al., Role of adjuvant chemotherapy in the treatment of surgically resected pediatric nonrhabdomyosarcomatous soft tissue sarcomas: A Pediatric Oncology Group Study. J Clin Oncol: official journal of the American Society of Clinical Oncology, (4): p Radiation Oncology Guidelines Version 3.0 RETURN 62 P age

63 Merchant T.E., et al., Brachytherapy for pediatric soft-tissue sarcoma. Int J Radiat Oncol Biol Phys, (2): p Arai Y, et al., Ewing's sarcoma: local tumor control and patterns of failure following limited-volume radiation therapy Int J Radiat Oncol Biol Phys, (6): p Grier, H.E, et al., Addition of ifosfamide and etoposide to standard chemotherapy for Ewing's sarcoma and primitive neuroectodermal tumor of bone. New Eng J Med, (8): p Paulussen M, et al., Results of the EICESS-92 Study: two randomized trials of Ewing's sarcoma treatment--cyclophosphamide compared with ifosfamide in standard-risk patients and assessment of benefit of etoposide added to standard treatment in high-risk patients. J Clin Oncol: official journal of the American Society of Clinical Oncology, (27): p Schuc, A, et al., Local therapy in localized Ewing tumors: results of 1058 patients treated in the CESS 81, CESS 86, and EICESS 92 trials. Int J Radiat Oncol Biol Phys, (1): p Schuck A, et al., Radiotherapy in Ewing's sarcoma and PNET of the chest wall: results of the trials CESS 81, CESS 86 and EICESS 92. Int J Radiat Oncol Biol Phys, (5): p Amichetti M, et al., A systematic review of proton therapy in the treatment of chondrosarcoma of the skull base. Neurosurgical Review, (2): p Gelderblom H, et al., The clinical approach towards chondrosarcoma. The Oncologist, (3): p Hug, E.B., et al., Proton radiation therapy for chordomas and chondrosarcomas of the skull base. Journal of Neurosurgery, (3): p Munzenrider J.E and N.J. Liebsch, Proton therapy for tumors of the skull base. Strahlentherapie und Onkologie: Organ der Deutschen Rontgengesellschaft, Suppl 2: p Riedel, R.F., et al., The clinical management of chondrosarcoma. Current Treatment Options in Oncology, (1-2): p Weber D.C, et al., Results of spot-scanning proton radiation therapy for chordoma and chondrosarcoma of the skull base: the Paul Scherrer Institut experience. Int J Radiat Oncol Biol Phys (2): p Ciernik, I.F., et al., Proton-based radiotherapy for unresectable or incompletely resected osteosarcoma. Cancer, (19): p Kempf-Bielack B, et al. Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). J Clin Oncol: official journal of the American Society of Clinical Oncology, (3): p RO-13~RECTAL CANCER Cancer Facts and Figures American Cancer Society, Gunderson, L.L. and J.E. Tepper, Clinical Radiation Oncology. 3rd Ed. 2012, Philadelphia, Pa.; London: Saunders. xvii, p Sauer, R., et al., Preoperative versus postoperative chemoradiotherapy for rectal cancer. New Eng J Med, (17): p Sauer, R., et al., Preoperative Versus Postoperative Chemoradiotherapy for Locally Advanced Rectal Cancer: Results of the German CAO/ARO/AIO-94 Randomized Phase III Trial After a Median Follow- Up of 11 Years. J Clin Oncol, (16): p Bosset, J.F., et al., Chemotherapy with preoperative radiotherapy in rectal cancer. The New Eng J Med, (11): p Guillem, J.G., et al., ct3n0 rectal cancer: potential overtreatment with preoperative chemoradiotherapy is warranted. J Clin Oncol, (3): p Ceelen, W.P., Y. Van Nieuwenhove, and K. Fierens, Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer. Cochrane database of systematic reviews, 2009(1): p. CD Gerard, J.P., et al., Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD J Clin Oncol (28): p Bosset, J.F., et al., Enhanced tumorocidal effect of chemotherapy with preoperative radiotherapy for rectal cancer: preliminary results--eortc J Clin Oncol (24): p Gerard, J.P, et al., Improved sphincter preservation in low rectal cancer with high-dose preoperative radiotherapy: the lyon R96-02 randomized trial. J Clin Oncol (12): p Radiation Oncology Guidelines Version 3.0 RETURN 63 P age

64 Lavertu S, et al., Endocavitary radiation therapy for rectal adenocarcinoma: 10-year results. Am J Clin Oncol, (5): p Rauch P, et al., Factors affecting local control and survival after treatment of carcinoma of the rectum by endocavitary radiation: a retrospective study of 97 cases. Int J Radiat Oncol Biol Phys, (1): p Gerard JP, et al., Sphincter preservation in rectal cancer. Endocavitary radiation therapy. Seminars in Radiation Oncology, (1): p Coatmeur O, et al., Treatment of T1-T2 rectal tumors by contact therapy and interstitial brachytherapy. Radiotherapy and Oncology (2): p Aumock A, et al., Treatment of rectal adenocarcinoma with endocavitary and external beam radiotherapy: results for 199 patients with localized tumors. Int J Radiat Oncol Biol Phys (2): p O'Connell, M.J., et al., Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. New Eng J Med (8): p Smalley, S.R., et al., Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT J Clin Oncol (22): p Thomas, P.R. and A.S. Lindblad, Adjuvant postoperative radiotherapy and chemotherapy in rectal carcinoma: a review of the Gastrointestinal Tumor Study Group experience. Radiotherapy and Oncology (4): p Krook, J.E., et al., Effective surgical adjuvant therapy for high-risk rectal carcinoma. New Eng J Med (11): p Fisher, B., et al., Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. Journal of the National Cancer Institute, (1): p NIH consensus conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA (11): p Wolmark, N., et al., Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02. Journal of the National Cancer Institute (5): p Prolongation of the disease-free interval in surgically treated rectal carcinoma. Gastrointestinal Tumor Study Group. New Eng J Med (23): p Steele, G.D., Jr., et al., Sphincter-sparing treatment for distal rectal adenocarcinoma. Ann Surg Oncol (5): p Benson, R., et al., Local excision and postoperative radiotherapy for distal rectal cancer. Int J Radiat Oncol Biol Phys (5): p Braendengen M, et al., Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol (22): p Hahnloser D, M.G. Haddock, and H. Nelson, Intraoperative radiotherapy in the multimodality approach to colorectal cancer. Surgical Oncology Clinics of North America (4): p , ix. Willett CG, B.G. Czito, and D.S. Tyler, Intraoperative radiation therapy. J Clin Oncol (8): p Nuyttens JJ, et al., High-dose-rate intraoperative radiotherapy for close or positive margins in patients with locally advanced or recurrent rectal cancer Int J Radiat Oncol Biol Phys (1): p Dresen R.C, et al., Definitive resection after IORT-containing multimodality treatment is the most important determinant for outcome in patients treated for locally recurrent rectal cancer. Ann Surg Oncol (7): p Lowy A.M, et al., Preoperative infusional chemoradiation, selective intraoperative radiation, and resection for locally advanced pelvic recurrence of colorectal adenocarcinoma. Ann Surg (2): p Alektiar K.M, et al., High-dose-rate intraoperative brachytherapy for recurrent colorectal cancer. Int J Radiat Oncol Biol Phys (1): p Guiney M.J, et al., Radiotherapy treatment for isolated loco-regional recurrence of rectosigmoid cancer following definitive surgery: Peter MacCallum Cancer Institute experience, Int J Radiat Oncol Biol Phys (5): p Radiation Oncology Guidelines Version 3.0 RETURN 64 P age

65 APPENDIX 2015 Radiation Oncology Guidelines RADIATION ONCOLOGY PROGRAM 2015 Procedure Code Update The American Medical Association (AMA) has established several 2015 code changes for radiation oncology. These changes include: (All code changes are effective 01/01/2015) All external beam treatment delivery codes have been rewritten. Codes for different levels of IMRT complexity have been created. A technology independent IGRT code has been created (which includes the previous Category III tracking code). IGRT has been bundled into IMRT delivery codes. Brachytherapy and Teletherapy planning codes have been revised and basic dosimetry calculations have been bundled into these codes. Nine codes traditionally used to report conventional radiation therapy treatment delivery have been deleted: CPT AMA CODE DESCRIPTION/DEFINITION Radiation treatment delivery, single treatment area, single port or parallel opposed ports, simple blocks or no blocks; 6-10 MeV ; MeV ; 20 MeV or greater Radiation treatment delivery, 2 separate treatment areas, 3 or more ports on a single treatment area, use of multiple blocks; 6-10 MeV ; MeV ; 20 MeV or greater Radiation treatment delivery, 3 or more separate treatment areas, custom blocking, tangential ports, wedges, rotational beam, compensators, electron beam; 6-10 MeV ; MeV ; 20 MeV or greater Conventional radiation therapy treatment delivery, performed with a megavoltage beam, is reported using the following three codes only. The code descriptors and criteria for reporting these codes have been revised: Radiation treatment delivery, single treatment area, single port or parallel opposed ports, simple blocks or no blocks; up to 5 MeV >1 MeV; simple Radiation treatment delivery, 2 separate treatment areas, 3 or more ports on a single treatment area, use of multiple blocks; up to 5 MeV >1 MeV; intermediate Radiation treatment delivery, 3 or more separate treatment areas, custom blocking, tangential ports, wedges, rotational beam, compensators, electron beam; up to 5 MeV >1 MeV; complex The energy level of the megavoltage beam no longer defines the complexity level of the codes. The criteria for reporting the newly revised conventional radiation therapy treatment delivery codes are different from the energy-based system previously used and are described below: Simple: All of the following criteria are met (and none of the complex or intermediate criteria are met): single treatment area; one or two ports; and two or fewer simple blocks. Intermediate: Any of the following criteria are met (and none of the complex criteria are met): two separate treatment areas; three or more ports on a single treatment area; or three or more simple blocks. Complex: Any of the following criteria are met: three or more separate treatment areas; custom blocking; tangential ports; wedges; rotational beam; field-in-field or other tissue compensation that does not meet IMRT guidelines; or electron beam. Red font = Deleted Blue font = New and strikethrough text = Revised RETURN CPT (Current Procedural Terminology) is a registered trademark of the American Medical Association (AMA). CPT five digit codes, nomenclature and other data are copyright 2015 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values or related listings are included in the CPT book. AMA does not directly or indirectly practice medicine or dispense medical services. AMA assumes no liability for the data contained herein or not contained herein.

66 APPENDIX 2015 Radiation Oncology Guidelines RADIATION ONCOLOGY PROGRAM 2015 Code Update Intensity Modulated Radiation Therapy (IMRT) Treatment Delivery Codes Code has been deleted: CPT AMA CODE DESCRIPTION/DEFINITION Intensity modulated treatment delivery, single or multiple fields/arcs, via narrow spatially and temporally modulated beams, binary, dynamic MLC, per treatment session IMRT treatment delivery is now reported using two new codes: CPT AMA CODE DESCRIPTION/DEFINITION Intensity modulated treatment delivery (IMRT), includes guidance and tracking, when performed; simple Intensity modulated treatment delivery (IMRT), includes guidance and tracking, when performed; complex Criteria for reporting the new IMRT delivery codes are: Simple: Any of the following: prostate, breast, and all sites using physical compensator-based IMRT. Complex: Includes all other sites if not using physical compensator-based IMRT. Compensator IMRT (0073T) has been deleted and will now be reported using 77385: CPT AMA CODE DESCRIPTION/DEFINITION Compensator-based beam modulation treatment delivery, of inverse planned treatment using 3 or 0073T more high resolution (milled or cast) compensator convergent beam modulated fields, per treatment session Guidance and tracking included in IMRT* The technical component (TC) of image guidance and tracking is now included in the IMRT delivery codes. When guidance and tracking are performed, the physician will only report the professional component (PC) of the new guidance and tracking code. Please note the complex conventional treatment delivery code (77412) now includes field-in-field techniques that are commonly used in treating breast cancer. This should not be confused with breast IMRT. *ASTRO Accessed: 09/18/2014 Red font = Deleted Blue font = New and strikethrough text = Revised RETURN NOTE: The Health Insurance Portability and Accountability Act (HIPAA) transaction and code set rules require the use of the medical code set that is valid at the time the service is provided. There is no grace period given to implement these changes changes are effective: 01/01/2015.

67 APPENDIX 2015 Radiation Oncology Guidelines RADIATION ONCOLOGY PROGRAM 2015 Code Update Image Guided Radiation Therapy (IGRT) Codes The following codes have been deleted: CPT 77421, CPT and 0197T. CPT should no longer be reported to describe the work associated with IGRT. CPT AMA CODE DESCRIPTION/DEFINITION Stereoscopic X-ray guidance for localization of target volume for the delivery of radiation therapy Ultrasonic guidance for placement of radiation therapy fields 0197T Intra-fraction localization and tracking of target or patient motion during delivery of radiation therapy (eg, 3D positional tracking, gating. 3D surface tracking), each fraction of treatment All guidance and tracking will be reported with the following new code: CPT AMA CODE DESCRIPTION/DEFINITION Guidance for localization of target volume for delivery of radiation treatment delivery, includes intrafraction tracking, when performed TC bundled into IMRT delivery codes* The TC of has been bundled into the new IMRT delivery codes (77385 and 77386). To report the professional component (PC) of guidance and tracking with IMRT, use with modifier 26. IGRT was not bundled into the conventional radiation therapy treatment delivery codes. Continue to report the global (TC and PC) of if image guidance is performed during conventional radiation treatment delivery. As in the past, do not report the TC of with 77371, or These codes have the work associated with image guidance included in their definition. *ASTRO Accessed: 09/18/2014 Red font = Deleted Blue font = New and strikethrough text = Revised RETURN NOTE: The Health Insurance Portability and Accountability Act (HIPAA) transaction and code set rules require the use of the medical code set that is valid at the time the service is provided. There is no grace period given to implement these changes changes are effective: 01/01/2015.

68 APPENDIX 2015 Radiation Oncology Guidelines RADIATION ONCOLOGY PROGRAM 2015 Code Update Teletherapy and Brachytherapy Isodose Planning Codes Three teletherapy codes (CPT 77305, CPT and CPT 77315) and three brachytherapy codes (CPT 77326, CPT and CPT 77328) have been deleted. CPT AMA CODE DESCRIPTION/DEFINITION Teletherapy, isodose plan; simple Teletherapy, isodose plan; intermediate Teletherapy, isodose plan; complex Brachytherapy isodose plan; simple Brachytherapy isodose plan; intermediate Brachytherapy isodose plan; complex Five new codes will be used to report these services. All five of these codes include the work associated with the basic dosimetry calculation. Do not report CPT with these codes: CPT AMA CODE DESCRIPTION/DEFINITION Teletherapy isodose plan; simple (1 or 2 unmodified ports directed to a single area of interest), includes basic dosimetry calculations Teletherapy isodose plan; complex (multiple treatment areas), includes basic dosimetry calculations Brachytherapy isodose plan; simple (calculation[s] made from 1 to 4 sources, or remote afterloading brachytherapy, 1 channel), includes basic dosimetry calculation(s) Brachytherapy isodose plan; intermediate (calculation[s] made from 5 to 10 sources, or remote afterloading brachytherapy, 2-12 channels), includes basic dosimetry calculation(s) Brachytherapy isodose plan; complex (calculation[s] made from over 10 sources, or remote afterloading brachytherapy, over 12 channels), includes basic dosimetry calculation(s) Red font = Deleted Blue font = New and strikethrough text = Revised RETURN NOTE: The Health Insurance Portability and Accountability Act (HIPAA) transaction and code set rules require the use of the medical code set that is valid at the time the service is provided. There is no grace period given to implement these changes changes are effective: 01/01/2015.

69 APPENDIX 2015 Radiation Oncology Guidelines Radiation Therapy G-Codes Replacing CY 2015 CPT Codes CMS has established the following set of G codes, for 2015, to report those services represented by the corresponding deleted 2014 codes. These are mandatory for Medicare only and optional for all other payors. The purpose of these codes, as described in CMS-1612-FC, is to aid in the revaluing of these services for future Medicare reimbursement. Medicare is delaying the use of the revised radiation therapy code set until CY 2016 when they will then be able to include proposals in the proposed rule for their valuation. All payment policies applicable to the CY 2014 codes will apply to this set of replacement G-codes. See list below: CY 2014 CY 2015 CPT HCPCS Long Descriptor G6001 Ultrasonic guidance for placement of radiation therapy fields G6002 Stereotactic X-ray guidance for localization of target volume for the delivery of radiation therapy G6003 Radiation treatment delivery, single treatment area, single port or parallel opposed ports, simple blocks or no blocks: up to 5MeV G6004 Radiation treatment delivery, single treatment area, single port or parallel opposed ports, simple blocks or no blocks: 6-10 MeV G6005 Radiation treatment delivery, single treatment area, single port or parallel opposed ports, simple blocks or no blocks: MeV G6006 Radiation treatment delivery, single treatment area, single port or parallel opposed ports, simple blocks or no blocks: 20 MeV or greater G6007 Radiation treatment delivery, 2 separate treatment areas, 3 or more ports on a single treatment area, use of multiple blocks; up to 5MeV G6008 Radiation treatment delivery, 2 separate treatment areas, 3 or more ports on a single treatment area, use of multiple blocks; 6-10 MeV G6009 Radiation treatment delivery, 2 separate treatment areas, 3 or more ports on a single treatment area, use of multiple blocks; MeV G6010 Radiation treatment delivery, 2 separate treatment areas, 3 or more ports on a single treatment area, use of multiple blocks; 20 MeV or greater G6011 Radiation treatment delivery, 3 or more separate treatment areas, custom blocking, tangential ports, wedges, rotational beam, compensators, electron beam; up to 5 MeV G6012 Radiation treatment delivery, 3 or more separate treatment areas, custom blocking, tangential ports, wedges, rotational beam, compensators, electron beam; 6-10 MeV G6013 Radiation treatment delivery, 3 or more separate treatment areas, custom blocking, tangential ports, wedges, rotational beam, compensators, electron beam; MeV G6014 Radiation treatment delivery, 3 or more separate treatment areas, custom blocking, tangential ports, wedges, rotational beam, compensators, electron beam; 20 MeV or greater G6015 Intensity modulated treatment delivery, single or multiple fields/arcs, via narrow spatially and temporally modulated beams, binary, dynamic MLC, per treatment session 0073T G6016 Compensator-based beam modulation treatment delivery of inverse planned treatment using 3 or more high resolution (milled or cast) compensator, convergent beam modulated fields, per treatment session 0197T G6017 Intra-fraction localization and tracking of target or patient motion during delivery of radiation therapy (eg, 3D positional tracking, gating, 3D surface tracking), each fraction of treatment RETURN NOTE: The Health Insurance Portability and Accountability Act (HIPAA) transaction and code set rules require the use of the medical code set that is valid at the time the service is provided. There is no grace period given to implement these changes changes are effective: 01/01/2015.