ADJUVANT RADIATION FOR MALIGNANT MELANOMA

Transcription

1 ADJUVANT RADIATION FOR MALIGNANT MELANOMA Effective Date: February 2014 The recommendations contained in this guideline are a consensus of the Alberta Cutaneous Tumour Team and are a synthesis of currently accepted approaches to management, derived from a review of relevant scientific literature. Clinicians applying these guidelines should, in consultation with the patient, use independent medical judgment in the context of individual clinical circumstances to direct care.

2 BACKGROUND The role of adjuvant radiation therapy in the management of melanoma remains unclear. It should rarely be employed for definitive treatment of a primary melanoma site. The main role of adjuvant radiation is the treatment of the nodal basin after resection of regionally advanced melanoma. Several nonrandomized studies have suggested that postoperative radiation to the neck or axilla after radical lymph node dissection decreases regional recurrence rates in node-positive patients. 1-3 Until larger randomized trials are conducted, it is reasonable to consider postoperative radiation therapy in patients with gross extra-capsular extension or multiple involved lymph nodes. 4 GUIDELINE QUESTION Should adjuvant radiation therapy be offered to patients with early stage melanoma who have been rendered disease-free following the resection of cutaneous melanomas and who are at high risk for subsequent recurrence? Should adjuvant radiation therapy be offered to patients with advanced stage melanoma? Should adjuvant radiation therapy be offered to patients with recurrent melanoma? What considerations should be made when treating patients with radiation therapy? DEVELOPMENT PANEL This guideline was reviewed and endorsed by the Alberta Cutaneous Tumour Team. Members of the Alberta Cutaneous Tumour Team include medical oncologists, radiation oncologists, surgical oncologists, dermatologists, nurses, pathologists, and pharmacists. Evidence was selected and reviewed by a working group comprised of members from the Alberta Provincial Cutaneous Tumour Team and a Knowledge Management Specialist from the Guideline Utilization Resource Unit. A detailed description of the methodology followed during the guideline development process can be found in the Guideline Utilization Resource Unit Handbook. SEARCH STRATEGY The MEDLINE (1966 through January 2011), CINAHL, Cochrane, ASCO Abstracts and proceedings, and CANCERLIT databases were searched. The search included practice guidelines, systematic reviews, meta-analyses, randomized controlled trials, and clinical trials. Search terms included: radiation or adjuvant radiation and malignant melanoma. PubMed was again searched in 2013 for evidence on radiation therapy in cutaneous melanoma. The search term melanoma was used and results were limited to clinical trials, published between January 2012 and January Citations were hand-searched for studies pertaining to radiation therapy, resulting in one new phase III clinical trial. Updates to the National Comprehensive Cancer Network guideline (2013) on melanoma were cross referenced with this guideline as well. Following a review of the evidence by the Alberta Cutaneous Tumour Team, no changes to the recommendations were made. Using the same search strategy, two relevant articles published between January 2013 and January 2014 were identified during the 2014 update. Following a review of the evidence by the Alberta Cutaneous Tumour Team, no changes were made to the recommendations. Page 2 of 9

3 TARGET POPULATION The recommendations outlined in this guideline apply to adults over the age of 18 years with malignant melanoma. Different principles may apply to pediatric patients. RECOMMENDATIONS Most patients with in-situ or early-stage melanoma (Stage 0; Stage 1A/B; Stage II, 1 mm thick with ulceration or Clark level IV, V or > 1 mm thick, any characteristic; and Stage III, sentinel node positive): There is no recommendation for the use of adjuvant radiation therapy, as most of these patients 5 will be cured by primary excision alone. Post-operative radiotherapy may be used after close or positive margins where further excision is not practical or possible, inoperative lentigo maligna, rapid or multiple recurrences or extensive perineural spread (as seen with Desmoplastic melanoma). Patients with Stage IIIC or Stage IV disease should be referred for the consideration of adjuvant 5 radiation therapy to improve local and regional control of their disease. Stage IIIC with multiple nodes involved or extranodal extension: consider radiation therapy to nodal basin Stage III in transit: consider radiation therapy Stage IV Metastatic: if disseminated (unresectable) with brain metastases, consider radiation for symptomatic patients Consider the following for patients with recurrence: Recurrence (true local scar): base treatment on stage of recurrence Recurrence (local, satellitosis, and/or in-transit): consider radiation therapy Recurrence (nodal): consider adjuvant radiation therapy Recurrence (distant): if disseminated (unresectable) with brain metastases, consider radiation for symptomatic patients If Interferon is to be part of the treatment regimen: Radiation should not be given concurrently. Interferon may act as a radiosensitizer, and patients receiving both may experience increased toxicities. Radiation therapy may be delayed until completion of the induction phase of interferon administration. DISCUSSION Surgery is the primary treatment of patients with stage I-III melanoma. However, high recurrence rates have prompted attempts to develop effective adjuvant therapies after primary local and regional surgical interventions. Primary indications for consideration of adjuvant radiation include nodal extracapsular extension (ECE), large lymph node size, multiple lymph nodes involved with metastatic disease, and recurrent disease after prior nodal surgery. Regional recurrence rates after surgical dissection alone when any one of these features is present range from 30-50%, although higher rates have been reported Additional high-risk 5 Page 3 of 9

4 features include macroscopic nodal disease, positive margins and head and neck lymph node location and consideration for patients with positive nodal disease who refuse dissection A retrospective study by Ballo and colleagues involving 160 patients who had surgery followed by radiotherapy (30 Gy in 6 Gy fractions two times per week) revealed 10-year actuarial local, regional, and locoregional control rates of 94%, 94%, and 91%, respectively, and 10-year actuarial disease-specific, disease-free, and distant metastasis-free survival rates of 48%, 42%, and 43%, respectively. 19,20 Similar control rates and survival rates have been reported from more recent retrospective studies Strojan, et al. (2010) published retrospective data showing significant improvements in regional control at two years with the use of adjuvant radiotherapy (60 Gy in 2 Gy fractions five times per week) as compared to surgery alone (78 vs. 56%; P=.015) among patients with regionally advanced melanoma to the neck and/or parotid. 23 A prospective randomized controlled trial by Agrawal, et al. (2009), among patients with clinically advanced, regional lymph node-metastatic disease (n=615), compared therapeutic lymphadenectomy and adjuvant radiotherapy with surgery alone and demonstrated a reduction in the regional recurrence rate (10.2 vs. 40.6%); furthermore, adjuvant radiotherapy was significantly associated with five-year regional control (P<.0001), distant metastasis-free survival (P=.0006), and disease-specific survival (P<.0001). 27 A more recent randomized trial compared adjuvant radiotherapy (48 Gy in 20 fractions) with observation, following lymphadenectomy among 217 patients with nodal metastases and a high risk of recurrence (based on number of nodes involved, extranodal spread, and maximum size of involved nodes). After a median follow-up of 40 months, the risk of lymph-node field relapse was found to be significantly reduced in the adjuvant radiotherapy group (20 relapses in RT vs. 34 in observation; HR 0.56, 95% CI ; p=.041). However, there were no differences in relapse-free survival (70 events vs. 73, HR 0.91, 95% CI ; p=.56) or overall survival (59 deaths vs. 47, HR 1.37, 95% CI ; p=.12). 28 The axillary control rate with adjuvant radiotherapy versus surgery alone has been reported to be as high as 87%. However, the risk of adjacent-field recurrences with the use of radiotherapy (OR 4.27, 95% CI ; p=0.02) should be considered when planning radiotherapy. 29 Current guidance from the National Comprehensive Cancer Network supports the use of adjuvant radiotherapy, based on lower level evidence. The guideline states that adjuvant radiation may be considered in special cases where adequate surgical treatment is not possible, for selected patients with desmoplastic melanoma with extensive neurotrophism, and for patients at significant risk of nodal basin relapse. The suggested regimen is Gy (2-6 Gy per fraction) over weeks. 30 DISSEMINATION Present the guideline at the local and provincial tumour team meetings and weekly rounds. Post the guideline on the Alberta Health Services website. Send an electronic notification of the new guideline to all members of CancerControl Alberta. MAINTENANCE A formal review of the guideline will be conducted at the Annual Provincial Meeting in If critical new evidence is brought forward before that time, however, the guideline working group members will revise and update the document accordingly. Page 4 of 9

5 CONFLICT OF INTEREST Participation of members of the Alberta Provincial Cutaneous Tumour Team in the development of this guideline has been voluntary and the authors have not been remunerated for their contributions. There was no direct industry involvement in the development or dissemination of this guideline. CancerControl Alberta recognizes that although industry support of research, education and other areas is necessary in order to advance patient care, such support may lead to potential conflicts of interest. Some members of the Alberta Provincial Cutaneous Tumour Team are involved in research funded by industry or have other such potential conflicts of interest. However the developers of this guideline are satisfied it was developed in an unbiased manner. REFERENCES 1 Gershenwald J, Thompson W, Mansfield P, Lee J. Multiinstitutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage I or II melanoma patients. J Clin Oncol 1999;17:976/83. 2 Balch C, Soong S, Ross M, et al. Long-term results of a multi-institutional randomized trial comparing prognostic factors and surgical results for intermediate thickness melanomas (1.0 to 4.0 mm). Intergroup Melanoma Surgical Trial. Ann Surg Oncol 2001;7: Cascinelli N, Morabito A, Santinami M, et al. Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk. Lancet 1998;351: Pawlik T, Sondak V. Malignant melanoma: current state of primary and adjuvant Treatment. Critical Reviews in Oncology/Hematology 2003; 45: National Comprehensive Cancer Network. Melanoma Guidelines, URL: professionals/physician_gls/pdf/melanoma.pdf 6 Lee RJ, Gibbs JF, Proulx GM, et al. Nodal basin recurrence following lymph node dissection for melanoma implications for adjuvant radiotherapy. Int J Radiat Oncol Biol Phys 2000;46: Calabro A, Singletary SE, Balch CM. Patterns of relapse in 1001 consecutive patients with melanoma nodal metastases. Arch Surg 1989;124: Byers RM. The role of modified neck dissection in the treatment of cutaneous melanoma of the head and neck. Arch Surg 1986;121: O Brien CJ, Coates AS, Petersen-Schaefer K, et al. Experience with 998 cutaneous melanomas of the head and neck over 30 years. Am J Surg 1991;162: Shen P, Wanek LA, Morton DL. Is adjuvant radiotherapy necessary after positive lymph node dissection in head and neck melanomas? Ann Surg Oncol 2000;7: Bowsher WG, Taylor BA, Hughes LE. Morbidity, mortality and local recurrence following regional node dissection for melanoma. Br J Surg 1986;73: Miller EJ, Daly JM, Synnestvedt M, Schultz D, Elder D, Guerry D. Loco-regional nodal relapse in melanoma. Surg Oncol 1992;1: Kretschmer L, Neumann C, Preuber K, Marsch WC. Superficial inguinal and radical ilioinguinal lymph node dissection in patients with palpable melanoma metastases to the groin. Acta Oncologica 2001;40:72 8. Page 5 of 9

6 14 Monsour PD, Sause WT, Avent JM, Noyes RD. Local control following therapeutic nodal dissection for melanoma. J Surg Oncol 1993;54: Ballo MT, Ang KK: Radiation therapy for malignant melanoma. Surg Clin North Am 2003;83: Ballo MT, Ang KK: Radiotherapy for cutaneous malignant melanoma: rationale and indications. Oncology (Williston Park) 2004;18:99-107; discussion , Bastiaannet E, Beukema JC, Hoekstra HJ. Radiation therapy following lymph node dissection in melanoma patients: treatment, outcome and complications. Cancer Treat Rev 2005;31: Stevens G, McKay MJ: Dispelling the myths surrounding radiotherapy for treatment of cutaneous melanoma. Lancet Oncol 2006;7: Ballo MT, Bonnen MD, Garden AS, et al, Adjuvant irradiation for cervical lymph node metastases from melanoma. Cancer 2003; 97: Ballo M, Zagars G, Gershenwald J, et al. A Critical Assessment of Adjuvant Radiotherapy for Inguinal Lymph Node Metastases from Melanoma. Annals of Surgical Oncology, 2004; 11(12): Beadle BM, Guadagnolo BA, Ballo MT, Lee JE, Gershenwald JE, Cormier JN, Mansfield PF, Ross MI, Zagars GK. Radiation therapy field extent for adjuvant treatment of axillary metastases from malignant melanoma. Int J Radiat Oncol Biol Phys Apr 1;73(5): Epub 2008 Sep Conill C, Valduvieco I, Domingo-Domènech J, Arguis P, Vidal-Sicart S, Vilalta A. Loco-regional control after postoperative radiotherapy for patients with regional nodal metastases from melanoma. Clin Transl Oncol Oct;11(10): Strojan P, Jancar B, Cemazar M, Perme MP, Hocevar M. Melanoma metastases to the neck nodes: role of adjuvant irradiation. Int J Radiat Oncol Biol Phys Jul 15;77(4): Epub 2009 Nov Wu AJ, Gomez J, Zhung JE, Chan K, Gomez DR, Wolden SL, Zelefsky MJ, Wolchok JD, Carvajal RD, Chapman PB, Wong RJ, Shaha AR, Kraus DH, Shah JP, Lee NY. Radiotherapy after surgical resection for head and neck mucosal melanoma. Am J Clin Oncol Jun;33(3): Guadagnolo BA, Myers JN, Zagars GK. Role of postoperative irradiation for patients with bilateral cervical nodal metastases from cutaneous melanoma: a critical assessment. Head Neck Jun;32(6): Mendenhall WM, Shaw C, Amdur RJ, Kirwan J, Morris CG, Werning JW. Surgery and adjuvant radiotherapy for cutaneous melanoma considered high-risk for local-regional recurrence. Am J Otolaryngol Jul-Aug;34(4): Agrawal S. Kane JM 3rd. Guadagnolo BA. Kraybill WG. Ballo MT. The benefits of adjuvant radiation therapy after therapeutic lymphadenectomy for clinically advanced, high-risk, lymph node-metastatic melanoma. Cancer. 115(24): , 2009 Dec Burmeister BH, Henderson MA, Ainslie J, et al. Adjuvant radiotherapy versus observation alone for patients at risk of lymph-node field relapse after therapeutic lymphadenectomy for melanoma: a randomised trial. Lancet Oncol Jun;13(6): Pinkham MB, Foote MC, Burmeister E, Thomas J, et al. Stage III Melanoma in the Axilla: Patterns of Regional Recurrence After Surgery With and Without Adjuvant Radiation Therapy. Int J Radiation Oncol Biol Phys. 2013; 86(4): Page 6 of 9

7 30 National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Melanoma. V URL: 31 Balch, C.M. et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009; 27(36): Page 7 of 9

8 APPENDIX AJCC 2009 (7th Edition) Anatomic Stage Groupings for Cutaneous Melanoma 31 5-year Survival T N M T N M Clinical Staging a Pathologic Staging b (%) 0 Tis N0 M0 0 Tis N0 M0 100% IA T1a N0 M0 IA T1a N0 M0 95% IB T1b N0 M0 IB T1b N0 M0 90% T2a T2a IIA T2b N0 M0 IIA T2b N0 M0 78% T3a T3a IIB T3b N0 M0 IIB T3b N0 M0 65% T4a T4a IIC T4b N0 M0 IIC T4b N0 M0 45% III Any T N > N0 M0 IIIA IIIB IIIC N1a N2a N1a N2a N1b N2b N2c N1b M0 66% 50% 27% Any T N2b N2c N3 IV Any T Any N M1 IV Any T Any N M1 13% a Clinical staging includes microstaging of the primary melanoma and clinical/radiologic evaluation for metastases. By convention, it should be used after complete excision of the primary melanoma with clinical assessment for regional and distant metastases. b Pathologic staging includes microstaging of the primary melanoma and pathologic information about the regional lymph nodes after partial (i.e., sentinel node biopsy) or complete lymphadenectomy. Pathologic stage 0 or IA patients are the exception; they do not require pathologic evaluation of their lymph nodes. Page 8 of 9

9 AJCC 2009 (7 th Edition) TNM Staging Categories for Cutaneous Melanoma 31 T Thickness (mm) Ulceration Status/Mitoses Tis NA NA T a: without ulceration and mitosis < 1/mm b: with ulceration or mitoses 1/mm T a: without ulceration b: with ulceration T a: without ulceration b: with ulceration T4 > 4.00 a: without ulceration b: with ulceration N Number of Metastatic Nodes Nodal Metastatic Burden N0 0 NA N1 1 a a: micrometastasis b b: macrometastais N2 2-3 a a: micrometastasis b b: macrometastais c: in transit metastases/satellites without metastatic nodes N3 4+ metastatic nodes, or matted nodes, or in transit metastases/ satellites with metastatic nodes M Site Serum LDH (lactate dehydrogenase) M0 No distant metastases not applicable M1a M1b M1c Distant skin, subcutaneous or nodal metastases Lung metastases All other visceral metastases Normal Normal Normal Elevated Any distant metastases a Micrometastases are diagnosed after sentinel lymph node biopsy. b Macrometastases are defined as clinically detectable nodal metastases confirmed pathologically. 2 2 Page 9 of 9