Where We Came From Frame-Based Spine Radiosurgery: 1995

Spine Radiosurgery John C Flickinger MD and Peter Gerszten MD Departments of Radiation Oncology and Neurological Surgery University of Pittsburgh Medical Center Pittsburgh, Pennsylvania

Where We Came From Frame-Based Spine Radiosurgery: 1995

Extracranial Stereotactic Radiosurgery Frame-based SRS Frameless Image-guided SRS

Dr. John Adler developed the CyberKnife (First treatment June 6, 1994)

First ever frameless spine radiosurgery case using the CyberKnife: 1997 T1 hemangioblastoma in a patient with VHL.

Our experience with Spine Radiosurgery in Pittsburgh began in 2001: The CyberKnife

Spine Radiosurgery Today: Many different technologies are currently available

Current Indications for Spine Radiosurgery In previously irradiated sites (i.e. salvage therapy ) As a primary treatment modality For medically inoperable patients As an adjunct to surgery For lesions not amenable to open surgery

Overall Clinical Outcomes: Metastases Long-term pain improvement 86% overall Radiographic control» Primary treatment 90%» Radiographic progression 88% Clinical improvement after progressive 84% neurological deficit

What does the current evidence support? Conventional Radiotherapy» 3 randomized trials (high quality evidence)» 4 prospective studies (moderate quality evidence)» Over 40 non-prospective data (low quality evidence)» Includes over 5,000 patients in the literature Stereotactic Radiosurgery» >45 single institution reports (as of January 2012)» No randomized data available to date

Evidence in the Literature for Radiosurgery What are the clinical outcomes of the current indications for radiosurgery for metastatic spine disease?» Despite the low quality of the available evidence, the reported outcomes are remarkably consistent.» 85-100% of reported patients experiencing effective palliation of pain.» 75-92% of patients experienced improvement of progressive neurologic symptoms after radiosurgery.

The Need for Class I Evidence: Radiation Therapy Oncology Group 0631 Phase II/III Study of Image-Guided Radiosurgery/SBRT for Localized Spine Metastases Phase II Component» 43 patients treated with 16 Gy single dose SBRT» (Accrual complete. ASTRO 2011 presentation.) Phase III Component» 240 patients randomized to 16 Gy single dose SBRT versus 8 Gy conventional single dose (2:1 ratio)

Purpose of RTOG 0631 Study Phase II component To determine the feasibility of successfully delivering image-guided radiosurgery/sbrt for localized spine metastases in an RTOG cooperative group setting. Phase III component To compare the efficacy of pain relief between spine radiosurgery/sbrt and conventional EBRT in patients with localized spine metastasis (1-3 sites). Primary endpoint Complete or partial pain relief at the treated index spine at 3 months after radiosurgery Secondary endpoints Rapidity and duration of pain response at the treated site(s) Overall quality of life; FACT-G, BPI, EQ-5D

RTOG 0631 Phase II/III Schema Solitary (1-3) spine metastasis Radiosurgery (16 Gy) Phase II (43 pts) feasibility Phase III (240 pts) Radiosurgery (16 or 18 Gy) EBRT (8 Gy single dose) Follow-up 1. Pain score & QoL q month 2. Clinical and neuro exams q month 3. Imaging (MRI) q 2 months

Target Volume for Metastasis Spinal cord volumes based on simulation CT and MRI image fusion 16 Gy in one fraction prescribed coverage at least 90% of GTV 80%-90% acceptable/minor variation <80% unacceptable/major deviation

Acute Adverse Events (NCI CTCAE v3.0) Grade 1-2 definitely, probably, or possibly related AEs in 11 pts (28%) back pain 4 headache, cough, palpitations 1 pruritus, bone pain 1 nausea 1 dysphagia 1 pharyngolaryngeal pain, neuropathy 1 extremity pain, neuropathy, dyspepsia 1 extremity/neck/back pain, neuropathy, dysphagia 1 Grade 3-4 definitely, probably, or possibly related AEs in 1 pt (3%) neck pain 1

Conclusions from RTOG Phase II Trial Despite the complexity of spine radiosurgery/sbrt, the phase II study results demonstrated its successful delivery and feasibility with acceptable toxicity in the cooperative group setting. The phase III component to assess pain relief and quality of life is now open and actively accruing patients. Radiosurgery (16 or 18 Gy) Solitary (1-3) spine metastasis 240 pts, 2:1 Randomization; Pain Relief @ 3 mo. EBRT (8 Gy)

Adoption of Spine Radiosurgery Parallels the way in which radiosurgery has been incorporated into the multimodality approach to intracranial lesions.» May avoid open surgery (and avoid associated morbidity).» Alters the actual surgery performed (i.e. extent of resection or approach). Allows for more minimally invasive separation surgery.» Integrated into the systemic therapy.» Used as a radiation boost after conventional fractionated radiotherapy for bulky or radioresistant tumors.» Neoadjuvant therapy (primary spine tumors such as chordomas) However, with certain issues unique to the spine.» Issues of spinal instability (i.e. biomechanics)» Combine with percutaneous fracture stabilization using methylmethacrylate.

Most Common Indication: e.g. Breast Cancer Pain recurrence after prior fractionated therapy

Combine Radiosurgery with Percutaneous Fracture Reduction and Fixation

Another issue unique to spine radiosurgery: Spinal Implants Concern has been raised of the ability to safely and accurately perform spine radiosurgery in post-surgical cases in which:» titanium instrumentation and/or» methylmethacrylate.have been implanted without using implanted fiducials for image guidance.

30% of our patients have spinal implants

We know what can safely be treated with SRS and what cannot.

Tomorrow: Radiosurgical Decompression?? Consideration of the Degree of Spinal Cord/Canal Compromise 0 1a 1b 1 1c 2 3

Intradural Malignant Tumors de novo Hemangioblastoma 35 year old school teacher. Developed right proximal leg pain. MRI revealed an intradural tumor. Biopsy positive for hemangioblastoma. Surgery would have been very difficult.

Case Example: de novo Hemangioblastoma 15 Gy in a single session. Long-term radiographic and symptomatic control. BETTER THAN SURGERY!

Spine Radiosurgery: Benign Tumors The role of stereotactic radiosurgery for the treatment of intracranial benign tumors is well established. There is now extensive experience with radiosurgery for malignant tumors of the spine. There is much less experience and more controversy regarding radiosurgery for benign tumors of the spine. This is the opposite of the development of intracranial radiosurgery, which began with the treatment of benign tumors.

SRS for Benign Tumors Differences between spine radiosurgery for malignant disease:» Lesions are often amenable to open surgery.» These lesions are often intradural.» Little precedence in Radiation Oncology for treating these lesions.» Paucity of data regarding doses and fractionation.» Indications are poorly understood. Pain? Radiographic control?» Patients have a longer life expectancy, causing special concerns for Late effects of radiation to normal structures (e.g. spinal cord) Concerns of radiation induced malignant transformation

Benign Tumors: Intradural Extramedullary Meningioma Schwannoma Neurofibroma

First large series: Dodd et al. 2006

Saghal et al. 2007

Pittsburgh Experience 2008 & 2012

Benign Tumors (N=120) Indications for radiosurgery» Pain 30» Primary treatment 22» Post-surgical 26» Progressive neurological deficit 15» Radiographic tumor progression 14 Follow-up: 3 months to 10 years (median 6 years) This length of follow-up allows for statements regarding late toxicities. Long-term pain improvement 83% Long-term radiographic tumor control 93%

Stanford Experience 2011

Stanford Experience 2011 103 total intradural extramedullary benign tumors» Meningioma 32» Neurofibroma 24» Schwannoma 47 25 patients with Neurofibromatosis Mean follow-up 33 months (up to 87 months)» Stable size 59%» Decrease size 40%» Increase size 1% Only 1 patient with a transient myelopathy at 9 months.

Summary for Benign Spine SRS While surgical extirpation remains the primary treatment option for most benign intradural spinal tumors, radiosurgery was demonstrated to have long-term clinical benefits for the treatment of these lesions. The long-term efficacy of radiosurgery for such tumors has now been established. Its role in patients with neurofibromatosis will also be further defined with greater clinical experience. Radiosurgery will transform the way that we treat benign tumors of the spine.

Complications

Spinal Cord Tolerance

Spinal Cord Tolerance to Reirradiation