Characteristics, treatment patterns, and survival outcomes of primary GI melanoma cases compared to cutaneous melanoma, SEER:1973-2015 Amanda Kahl, MPH Mary E. Charlton, PhD, Imran Hassan, MD, Paolo Goffredo, MD, Catherine Chioreso, MPH, & Chi Lin, MD Oral Presentation, NAACCR June 14, 2018
Background Melanoma: ~10% of all primary cancer diagnoses in US 5 th and 6 th most common cancer in males and females Rare cases of primary gastrointestinal (GI) melanoma Reported to arise from mucosal membranes of the Esophagus Stomach Small intestine Colon Rectum Anus
Background 60% of metastatic skin melanomas have GI involvement at autopsy HOWEVER, several studies reported GI melanoma in the absence of skin melanoma But HOW?? Stem cells differentiating into melanocytes in the GI tract Cell migration
Primary GI Melanoma Most studies of GI melanoma have been based on case series Population-based cancer registries allow for examination of rare cancers over long periods of time
Study objective Compare characteristics, treatment, and survival between skin melanoma and primary GI melanoma Including sites of the esophagus, stomach, small intestine, colon, rectum, and anus
INCLUSION CRITERIA Diagnosed between 1973-2015 Histology of 8720-8799 GI melanoma sites: Esophagus (C150-C159) Stomach (C160-C169) Small intestine (C170-C179) Colon (C180-C189, C260) Rectum (C199, C209) Anus (C210, C211, C212, C218) Skin melanoma: C440-C449 First primary malignant melanoma: - GI melanoma N=828 - Skin melanoma N=304,797 Not reported via autopsy or death certificate - GI melanoma N=827 - Skin melanoma N=304,082 Ages 18-100 - GI melanoma N=827 - Skin melanoma N=302,194 Excluded: GI melanoma N=1 Skin melanoma N=715 Excluded: GI melanoma N=0 Skin melanoma N=1,888
Methods SEER*Stat used to extract patient, tumor and treatment variables Statistical analysis performed in SAS Chi-square tests for bivariate analyses Cause-specific Survival Cox proportional hazard models Incidence rates (1973-2015) were calculated in SEER*Stat and analyzed in Joinpoint
Results
GI Melanoma Incidence Rate, SEER 18 1973-2015
Skin Melanoma vs GI Melanoma Patient characteristics between GI melanoma and skin melanoma, 1973-2015 Cutaneous Melanoma GI Melanoma (N=302,194) (N=827) N % N % p-value Age at diagnosis 18-49 98,994 33% 95 12% <0.0001 50-69 125,842 42% 327 40% 70-100 77,358 26% 405 49% Sex Female 135,090 45% 483 58% <0.0001 Male 167,104 55% 344 42% Race White 285,387 94% 695 84% <0.0001 Non-White 16,807 6% 132 16% Married Yes 156,993 52% 434 53% 0.762 No 145,201 48% 393 48% Year of diagnosis 1973-1987 26,754 9% 68 8% 0.973 1988-1994 23,102 8% 62 8% 1995-2001 47,936 16% 130 16% 2002-2008 93,313 31% 259 31% 2009-2015 111,089 37% 308 37%
Skin Melanoma vs GI Melanoma Tumor characteristics between patients with GI melanoma and skin melanoma, 1973-2015 Cutaneous Melanoma GI Melanoma (N=302,194) (N=827) N % N % p-value SEER Summary Localized 248,669 82% 268 32% <0.0001 Stage Regional 28,033 9% 206 25% Distant 11,675 4% 260 31% Unstaged 13,817 5% 93 11% Tumor Size* <2 mm/cm 216,272 72% 85 10% - 2-<5 mm/ cm 24,789 8% 251 30% >=5 mm/cm 10,816 4% 176 21% Unknown 50,317 17% 315 38% *Tumor size is thickness in mm for cutaneous melanoma and size in cm for GI melanom
Skin Melanoma vs GI Melanoma Treatment characteristics between patients with GI melanoma and skin melanoma, 1988-2015 Surgery* Cutaneous Melanoma GI Melanoma (N=257,391) (N=827) N % N % p-value Local tumor 228562 83% 293 38.6 <0.000 excision 1 Major resection 25595 9% 254 33.5 Surgery, NOS 1500 1% 23 3% None or local tumor destruction only 18750 7% 188 25% Unknown 1033 0.4% 1 0.2% Radiation* Yes 6212 2% 154 20% <0.000 1 No/Unknown 269228 98% 605 80% Chemotherap Yes 5437 2% 151 20% <0.000 y* *Due to the large number of unknown surgery for cases diagnosed prior to 1988, they were excluded No/Unknown from the treatment 270003 variables 98% 608 80% 1
Anorectal vs Other GI site Melanoma Characteristics between anorectal and other GI site melanoma, 1973-2015 Anorectal Melanoma Other GI Melanoma Sites (N=688) (N=139) N % N % p- value GI cancer sites Esophagus - - 53 38% - Stomach - - 27 19% Intestine - - 38 27% Colon - - 21 15% Rectum 275 40% - - Anus 413 60% - -
Anorectal vs Other GI site Melanoma Patient characteristics between anorectal and other GI site melanoma, 1973-2015 Anorectal Melanoma Other GI Melanoma Sites (N=688) (N=139) N % N % p- value Age at diagnosis 18-49 79 12% 16 12% 0.920 50-69 270 39% 57 41% 70-100 339 49% 66 48% 0.000 3 Sex Female 421 61% 62 45% Male 267 39% 77 55% Race White 572 83% 123 89% 0.116 Non-White 116 17% 16 12% Married Yes 361 53% 73 53% 0.992 No 327 48% 66 48% Year of diagnosis 1973-1987 54 8% 14 10% 0.507 1988-1994 52 8% 10 7% 1995-2001 109 16% 21 15%
Anorectal vs Other GI site Melanoma Tumor characteristics between anorectal and other GI site melanoma, 1973-2015 Anorectal Other GI Melanoma Melanoma Sites (N=688) (N=139) N % N % SEER Summary Localized 228 33% 40 29% Stage Regional 183 27% 23 17% Distant 200 29% 60 43% Unstaged 77 11% 16 12% Tumor Size <2 cm 83 12% 2 1% 2-<5 cm 222 32% 29 21% >=5 cm 128 19% 48 35% Unknown 255 37% 60 43% p- value 0.005 4 <. 0001
Anorectal vs Other GI site Melanoma Treatment characteristics between between anorectal and other GI site melanoma, 1988-2015 Surgery* Other GI Anorectal Melanoma Melanoma Sites (N=688) (N=139) N % N % p-value Local tumor excision Major resection 183 29% 71 57% Surgery, NOS 22 4% 1 1% None or local tumor destruction only 289 46% 4 3% <.0001 139 22% 49 39% Unknown 1 0% - - Radiation* Yes 136 22% 18 14% 0.073 No/Unknown 498 79% 107 86% Chemotherap y* Yes 126 20% 25 20% 0.974 No/Unknown 508 80% 100 80% *Due to the large number of unknown surgery for cases diagnosed prior to 1988, they were excluded from the treatment variables
Kaplan Meier Cause-Specific Survival Curves
Survival of GI melanoma and skin melanoma patients, 1973-2015
Survival of localized GI melanoma and skin melanoma patients, 1973-2015 Localized
Survival of regional GI melanoma and skin melanoma patients, 1973-2015 Regional
Survival of distant GI melanoma and skin melanoma patients, 1973-2015 Distant
Cause-Specific Survival (CSS) Hazard Models
CSS adjusted hazard model including both GI melanoma and skin melanoma 1988-2015 (N=228,927) *Surgery NOS or Unknown Surgery; Unstaged, and Unknown size were excluded from model All cases HR 95% CI Cancer Type Cutaneous Melanoma 0.29 (0.25, 0.33) Anorectal Melanoma 1.00 REF Other GI site Melanoma 0.58 (0.42, 0.81) Age at diagnosis 18-49 0.37 (0.35, 0.38) 50-69 0.55 (0.53, 0.56) 70-100 1.00 REF Sex Female 0.67 (0.65, 0.69) Male 1.00 REF Race White 1.00 REF Non-White 0.74 (0.68, 0.80) Married Yes 1.00 REF No 1.08 (1.05, 1.11) Year of diagnosis 1988-1994 1.00 REF 1995-2001 0.85 (0.80, 0.89) 2002-2008 0.82 (0.78, 0.87) 2009-2015 0.76 (0.71, 0.81) SEER Summary Stage Localized 1.00 REF
CSS adjusted hazard model including both GI melanoma and skin melanoma 1988-2015 (N=228,927) *Surgery NOS or Unknown Surgery; Unstaged, and Unknown size were excluded from model All cases HR 95% CI Surgery Local tumor excision 1.00 REF Major resection 1.37 (1.30, 1.44) None or local tumor destruction only 1.54 (1.41, 1.68) Radiation Yes 1.00 REF No/Unknown 0.44 (0.41, 0.46) Chemotherapy Yes 1.00 REF No/Unknown 0.43 (0.41, 0.46)
CSS adjusted hazard model of GI melanoma 1988-2015 (N=440) *Surgery NOS or Unknown Surgery; Unstaged, and Unknown size were excluded from model GI Melanoma HR 95% CI Cancer Type Anorectal Melanoma 1.00 REF Other GI site Melanoma 0.92 (0.63, 1.34) Age at diagnosis 18-49 0.56 (0.38, 0.84) 50-69 0.88 (0.67, 1.15) 70-100 1.00 REF Sex Female 1.02 (0.80, 1.32) Male 1.00 REF Race White 1.00 REF Non-White 1.12 (0.82, 1.53) Married Yes 1.00 REF No 0.82 (0.65, 1.05) Year of diagnosis 1988-1994 1.00 REF 1995-2001 0.98 (0.59, 1.62) 2002-2008 0.82 (0.51, 1.32) 2009-2015 0.72 (0.44, 1.16) SEER Summary Stage Localized 1.00 REF
CSS adjusted hazard model of GI melanoma 1988-2015 (N=440) *Surgery NOS or Unknown Surgery; Unstaged, and Unknown size were excluded from model GI Melanoma HR 95% CI Tumor Size <2 cm 1.00 REF 2-<5 cm 1.13 (0.80, 1.61) >=5 cm 1.07 (0.72, 1.59) Surgery Local tumor excision 1.00 REF Major resection 0.92 (0.67, 1.27) None or local tumor destruction only 1.62 (1.04, 2.51) Radiation Yes 1.00 REF No/Unknown 1.08 (0.77, 1.52) Chemothera py Yes 1.00 REF No/Unknown 1.03 (0.74, 1.43)
Conclusions Incidence of GI melanoma has increased over time Skin melanoma has better prognosis overall and at every stage compared to GI melanoma Local tumor excision is no better than major resection for GI melanoma
Limitations & Strengths Limitations Small number of GI melanomas in individual sites Cases with GI melanoma may have undiagnosed primary skin melanoma Chemotherapy and radiation variables have sensitivity of 68% and 80%, respectively Strengths SEER data provide detailed information about cancer stage and treatment at time of diagnosis One of the first population based studies that characterizes the epidemiology, treatment, and survival of primary GI melanoma that includes sites of the esophagus, stomach, small intestine, colon, rectum, and anus compared to skin melanoma.
Questions? Thank you Contact information: amanda-kahl@uiowa.edu