Radiation Oncology/Melanoma/Overview

Malignant Melanoma Overview Overview Lentigo maligna - type of melanoma in-situ, induced by long-term cumulative UV injury. Slow horizontal growth of atypical melanocytes, that are partially replacing the basal layer of epidermis, with no evidence of dermal invasion Lentigo maligna melanoma (10-15%) - arise from lentigo maligna precursor lesion. Most benign behavior. Occupational sun exposure, frequently on head and neck. Typically in the elderly Superficial spreading melanoma (70%) - often arise from a pigmented dysplastic nevus. Associated with intermittent sun exposure, most common on trunk and extremities. Initial radial growth over many years has 5% metastatic potential; following vertical growth has 35-80% metastatic potential Nodular melanoma (10-15%) - most malignant type. Arises de novo. Early vertical growth. Acral lentiginous melanoma (5%) - occur on palms, soles, and subungal areas. High incidence in blacks, asians, and hispanics. Commonly metastatic Desmoplastic melanoma (1-3%) - pronounced neurotropism, and locally aggressive behavior. Frequent local recurrences, but lymph and distal mets are rare. Often amelanotic mucosal melanoma (1%) - arise from mucosal epithelium of respiratory, GI and GU tracts ocular melanoma (5%) - arise mostly in uvea or conjunctiva NCDB; 1998 (1985-1994) 9781962 -- "The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society." (Chang AE, Cancer. 1998 Oct 15;83(8):1664-78.) Population study. 84,836 cases of melanom reported to National Cancer Data Base Outcome: cutaneous 91.2%, ocular 5.2%, mucosal 1.3%, unknown primary 2.2% Cutaneous: Stage 0 15%, Stage I 48%, Stage II 23%, Stage III 9%, Stage IV 5% Ocular: uveal 85%, conjunctival 5%, other sites 10% Mucosal: H&N 55%, female genital tract 18%, anal/rectal 24%, urinary tract 3% Lentigo maligna Subtype of melanoma in-situ Usually occurs in elderly patients, usually on the face Slow horizontal growth. May progress to lentigo maligna melanoma Treatment is surgery with negative margins. When surgery is undesirable, RT or topical Imiquimod may be used Prevention Sunscreen: Australia (1992-6) -- "Reduced Melanoma After Regular Sunscreen Use: Randomized Trial Follow-Up" (Green AC, J Clin Oncol online early release 6 December 2010) 1621 pts (ages 25-75) randomized to daily vs discretionary use of sunscreen application to head and arms in combination with beta carotene or placebo supplements. Followed through 2006. 11 new primary melanomas in the daily sunscreen group vs 22 in the discretionary group (HR=0.50). Reduction in invasive melanomas (3 vs 11) was substantial compared with preinvasive melanomas. Conclusion: Melanoma may be preventable by regular sunscreen use in adults. Adjuvant systemic therapy Interferon alfa 2b: EORTC 18952, 2005 (1996-2000) - 16198768 — "Post-surgery adjuvant therapy with intermediate doses of interferon alfa 2b versus observation in patients with stage IIb/III melanoma (EORTC 18952): randomised controlled trial." Eggermont AM et al. The Lancet 2005; 366:1189-1196. 1388 pts. Thickness > 4mm, Stage IIb-III. Randomized to 1) 13 months or 2) 25 months of IFN-alfa-2b vs 3) observation. Median f/u 4.6 yrs. For 25-month group, 7.2% increase in distant metastases free interval (S.S.) and 5.4% increase in OS (p=0.12); for 13-month, N.S. difference for DMFI and OS. 18% of pts went off study due to toxicity or refusal of treatment. Conclusion: does not improve outcome. Autoimmunity as a prognostic factor: Hellenic Cooperative Oncology Group, 2006 (1998-2004) — "Prognostic Significance of Autoimmunity during Treatment of Melanoma with Interferon." Gogas H et al. N Engl J Med Feb 16 2006; 354:709-718. 200 pts (subgroup of a larger study) receiving interferon alfa-2b after surgery for Stage IIB, IIC, or III melanoma. Tested blood for the presence of antithyroid, antinuclear, anti-DNA, and anticardiolipin autoantibodies before and after treatment. Median f/u 45 mo. Autoantibodies in 26% of pts. 108 of 148 pts without autoantibodies had a relapse (median RFS 16 mo) vs 7 of 52 pts with autoantibodies (median RFS not reached). Median time to detection of autoantibodies was after 3 mo of treatment. Conclusion: development of autoimmunity was an independent prognostic factor for improved RFS and OS. Supportive Care Denmark Psychoeducation (1991-2001) Randomized. 262 patients, primary malignant melanoma, T1-4N1-2aM0. Arm 1) control vs. Arm 2) six weekly 2-hour sessions of psychoeducation. Replication study of UCLA study 2007 18089864 -- "Survival after a psychoeducational intervention for patients with cutaneous malignant melanoma: a replication study." (Boesen EH, J Clin Oncol. 2007 Dec 20;25(36):5698-703.) Outcome: No difference for OS or for recurrence; however, nonparticipants had 2x higher death rate Conclusion: Psychoeducation doesn't increase survival UCLA (1985-1986) Randomized. 68 patients. Stage I-II melanoma, surgical treatment only (wide excision, some with LND). Arm 1) controls vs. Arm 2) 6 week structured psychiatric group intervention 1993 8357293 -- "Malignant melanoma. Effects of an early structured psychiatric intervention, coping, and affective state on recurrence and survival 6 years later." (Fawzy FI, Arch Gen Psychiatry. 1993 Sep;50(9):681-9.) Outcome: Death rate control 29% vs. intervention 9% (SS); recurrence rate 38% vs. 21% Poor predictors: male, greater Breslow depth Conclusion: Psychiatric intervention had beneficial impact on survival Treatment toxicity Lymphedema after radiotherapy: Using hypofractionated RT At 5-yrs (needing compressive device, surgery, or medical treatment): Cervical - 11% Axillary - 30% Groin - 39% From 16814209, 2006 — "Dispelling the myths surrounding radiotherapy for treatment of cutaneous melanoma." Stevens G et al. Lancet Oncol. 2006 Jul;7(7):575-83. Review University of Florida; 2008 18260153 -- "Adjuvant radiotherapy for cutaneous melanoma." (Mendenhall WM, Cancer. 2008 Mar 15;112(6):1189-96.) Moffitt Cancer Center; 2008 18596675 -- "Radiation therapy as primary and adjuvant treatment for local and regional melanoma." (Berk LB, Cancer Control. 2008 Jul;15(3):233-8.) Auckland, New Zealand; 2006 16814209 -- "Dispelling the myths surrounding radiotherapy for treatment of cutaneous melanoma." (Stevens G, Lancet Oncol. 2006 Jul;7(7):575-83.) Groningen, Netherlands; 2005 15707701 -- "Radiation therapy following lymph node dissection in melanoma patients: treatment, outcome and complications." (Bastiaannet E, Cancer Treat Rev. 2005 Feb;31(1):18-26. Epub 2004 Nov 18.) MD Anderson; 2004 14768409 Full text — "Radiotherapy for cutaneous malignant melanoma: rationale and indications." Ballo MT et al. Oncology (Williston Park). 2004 Jan;18(1):99-107 Recommend RT to primary for: desmoplastic melanoma, positive margins, locally recurrent disease, Brewslow > 4 mm with ulceration or satellitosis Recommend RT to nodes for: extracapsular extension, >= 4 involved nodes, lymph node >= 3 cm in size, cervical lymph node location, recurrent nodal disease, sentinel lymph node positive but dissection not planned Dutch Melanoma Working Party, 1999 10465575 -- "Consensus on the management of malignant melanoma of the skin in The Netherlands. Dutch Melanoma Working Party." (Kroon BB, Melanoma Res 1999 Jun;9(3):207-12.) RT Utilization CCORE Australia; 2004 15022299 -- "Estimation of an optimal radiotherapy utilization rate for melanoma: a review of the evidence." (Delaney G, Cancer. 2004 Mar 15;100(6):1293-301.) Evidence-based estimate for proportion of patients who should receive RT Estimate: 23%. New South Wales utilization 13%, American College of Surgeons utilization 6%, SEER data 1% Conclusion: Shortfall in the use of RT in the treatment of melanoma Quality of Care American College of Surgeons; 2009 (2004-2005) 19826131 -- "National assessment of melanoma care using formally developed quality indicators." (Bilimoria KY, J Clin Oncol. 2009 Nov 10;27(32):5445-51. Epub 2009 Oct 13.) Development of 26 valid quality indicators assessing structure, process, and outcome. 10 of these assessed at 1249 hospitals using NCDB registry data Outcome: Adherence at patient level 12-96%, at hospital level 4-83%. Most hospitals adherent with <=50% of indicators Conclusion: Considerable variation in quality of melanoma care in the U.S. Rush Medical Center; 2008 18600380 -- "Adverse outcomes associated with noncompliance with melanoma treatment guidelines." (Erickson Foster J, Ann Surg Oncol. 2008 Sep;15(9):2395-402. Epub 2008 Jul 4.) Retrospective. 327 patients with cN0 melanoma. Compliance with NCCN guidelines assessed. Mean F/U 4.2 years Outcome: Margin non-compliance 28%, lymph node non-compliance 17%. Postop complications: margin compliance 10% vs noncompliant 30% (SS); lymph node compliant 13% vs. non-compliant 33% (SS). Locoregional recurrence: margin compliant 6% vs non-compliant 24% (SS); lymph node compliant 6% vs non-compliant 33% (SS). 10-year OS margin compliant 84% vs. noncompliant 73% (SS). 10-year OS lymph node compliant 91% vs. noncompliant 47% (SS) Conclusion: Compliance with NCCN guidelines seems to improve outcome and decrease morbidity