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8595 Background: Use of adjuvant systemic therapy in patients with stage III melanoma is widely known to be variable based upon multiple factors such as patient age and comorbidities as well as the preference and even geographic location of the oncologist and patient. The purpose of this study was to compare the use of adjuvant therapy among patients treated in teaching hospitals and community hospitals. Methods: The study population consisted of patients with stage III melanoma enrolled into the National Cancer Database (NCDB) between 2000-2008. Patients were selected based upon surgery as the first course of therapy which resulted in a total of 27,353 eligible for analysis. The study population was then categorized into those who were treated at Teaching Hospitals (TH) including National Cancer Institute-designated cancer centers or Community Hospitals (CH). Multiple variables including age, median household income, insurance status, race and overall survival were compared between patients in the two hospital groups. Results: The overall proportion of stage III patients who received adjuvant systemic therapy was approximately 30%. There was no difference in the proportion of patients receiving adjuvant systemic therapy between patients treated in TH as compared to CH, and there was no obvious trend towards increased use over time. Of interest was that the cohort of patients designated as being treated at TH had a higher proportion of patients less than 70 years old as compared to CH. Median household income was found to be higher in patients treated at TH. Finally, despite the observation that the proportion of patients who received adjuvant therapy was not different, there a significantly higher 5-year overall survival in patients treated at TH as compared to CH. Conclusions: Although the proportion of patients who received adjuvant systemic therapy was comparable in TH and CH, there was a significant increase in 5-year overall survival within TH. Additional factors such as age, lesser comorbidities, more favorable socioeconomic factors or other unmeasured factors such as type of adjuvant therapy or whether adjuvant therapy was completed may have contributed to the improved survival in patients treated at TH.

8551 Background: Patients with regionally disseminated malignant cutaneous melanoma, stage III, have a variable prognosis with reported 5-year survival of 24-67%, depending on subcategory. There is...

8506 Background: High dose IFNalfa2b, according to the ECOG 1684 schedule, is the only approved adjuvant treatment for stage III melanoma. The risk/benefit profile has limited its use, while effica...

8556 Background: Patients with advanced (AJCC Stage III & IV) malignant melanoma (MM) have variable outcomes despite similar stage. Defining prognostic factors is important to identify patients mos...

8506b Background: EORTC 18991 is the largest adjuvant trial ever conducted in stage III melanoma. It assessed the efficacy and toxicity of long-term PEG-IFN vs Observation (Obs.). Methods: PEG-IFN (Induction at 6µg/Kg/wk, sc, 8 weeks; followed by Maintenance at 3µg/Kg/wk, sc) for a total treatment duration of up to 5 years was compared to Obs. in 1256 patients (pts) with stage III melanoma (anyTN1-2M0 without in-transit metastases). Randomization was stratified for nodal involvement N1 (microscopic) vs N2 (palpable nodes), # of nodes, Breslow and ulceration of primary, sex and center. Distant metastasis-free survival (DMFS) was the primary endpoint. Relapse-free survival (RFS) was the pre-specified regulatory primary endpoint. Overall survival (OS) was the secondary endpoint. Intent-to-treat analysis was performed Results: Median follow-up was 7.6 yrs is shown in the table. Conclusions: Long-term PEG-IFN therapy in stage III melanoma had a significant and sustained impact on RFS, but not on DMFS and OS. P...

9039 Background: This is a pilot study evaluating of high-risk melanoma patients (pts) treated with peptide-DC vaccine after lymphadenectomy (LND). DC vaccination was designed to induce the immune response against melanoma antigens in melanoma pts who remain at high risk of dissemination after LND. Methods: DCs were generated from the bone marrow with the use GM-CSF, SCF, FLT3-L and TNFa or from peripheral blood adherent monocytes with GM-CSF and IL-4. DCs pulsed with HLA-A2-binding TYR, MART-1 and gp100 peptides and/or HLA-A1-binding MAGE-1, MAGE-3 peptides, tumor lysate if available, or with tracer antigen keyhole limpet hemocyanin (KLH), were injected sc 9 times within 8 months (mos). Boost injections were performed after 12 and 24 mos. Vaccinated pts were matched to unvaccinated controls (22 of 587) by sex, number of metastatic lymph nodes, extracapsular involvement, completion or therapeutic LND, Breslow stage (T), and ulceration. Results: HLA-A2+, -A1+ or -A3+ melanoma pts (n=22), stage III, N1b-N3, enrolled between Sept. 2002 and Apr. 2004, received 5–16 vaccinations (median: 11) within 2 yrs. Cutaneous delayed type hypersensitivity (DTH) to melanoma peptides was induced in 12 of 22 pts. Peptide-specific IFNg producing CD8+ cells were detected in peripheral blood of 13 of 19 pts after vaccination. At least one of these responses to melanoma antigens was elicited in 17 of 22 pts. DTH to KLH was positive in 15 of 22 pts. Nine vaccinated pts are free of disease, and 1 is stable by Dec. 2008 (follow up is 58–76 mos after LND). Survival analysis for vaccinated pts and matched controls is presented in the Table . Conclusions: The DC/peptide vaccine elicited immune responses to melanoma antigens. Vaccinated pts had clinically substantially longer overall survival (OS) and disease free survival (DFS) than matched control. OS was associated with the immune responsiveness to melanoma antigens and to KLH. [Table: see text] No significant financial relationships to disclose.

9069 Background: Follow up (F/U) of patients (pts) with AJCC stage III melanoma but with NED is currently empiric with respect to frequency of clinical exams, F/U duration, and diagnostic tests. Data-based F/U guidelines are needed. Methods: Clinical records of 429 pts with stage III NED pts seen at MSKCC between 1998 and 2002 and who ultimately relapsed were reviewed retrospectively to evaluate: site and date of 1st relapse, interval between the stage III NED and 1st relapse; how the 1st relapse was detected, date of death or last F/U. We also determined the overall 5 yr relapse-free survival (RFS) of all stage III pts seen at MSKCC during this period. Results: The overall 5 yr RFS for stage IIIA, B, and C patients at MSKCC was: 52%, 29%, and 15%, respectively. Among the relapsing pts, 280 had adequate F/U to be evaluable for all parameters (35 stage IIIA, 155 stage IIIB, 90 stage IIIC). The site of 1st relapse was local/in-transit (28%), regional nodal (20%), or systemic sites (52%). The most common sites of 1st systemic relapse were lung, liver, brain. There were significant differences among substages. First relapses were detected by the pt or family, MD, or by screening radiological tests in 52%, 19%, and 29% of cases, respectively. Multivariate analysis revealed better overall survival (OS) was not associated with time to relapse but was associated with younger age and if 1st relapse was: a) local/in-transit or nodal, b) asymptomatic, or c) resectable. By noting when the risk for 1st local/intransit, nodal, or systemic (lung, liver, brain) relapse became sufficiently low ( [Table: see text] No significant financial relationships to disclose.

Radiation therapy has several roles in the management of stage III melanoma. Perhaps the most controversial is in the post-operative setting where several retrospective studies and one prospective trial have suggested that radiation therapy results in a reduction in regional recurrence. On the basis of this and the fact that late toxicity is not increased, many cancer centres have adopted the use of radiation therapy in “high risk” patients with large nodes, multiple node involvement and the presence of extracapsular extension. The benefit of radiation therapy for this indication remains to be proven in a randomised trial and the outcome of the Trans Tasman Radiation Oncology group/Australian and New Zealand Melanoma Trials Group in settling this question is awaited. At the present time the only clear indications for post-operative radiation therapy are in those patients where the dissection may reveal an inadequate number of dissected nodes, those with positive margins, tumour spill at surgery or where disease has already recurred after a previous dissection. The area which is gaining more interest is the role of radiation therapy in the pre-operative setting for bulky, tethered or fixed nodal disease where the use of such therapy can not only result in significant reduction in tumour volume, thus aiding resection, but also separate out patients at high risk of metastatic disease where a major operation may be counterproductive to quality of life. If patients having this approach do develop distant metastases during or shortly after receiving radiation therapy, they may still obtain reasonable palliation with the use of such local therapy.

9069 Background: An important part in the treatment planning for metastatic melanoma is an evaluation of the presence or absence of distant melanoma metastases. However, melanoma has the well-known...

Background: The heterodimeric cytokine interleukin-12 (IL-12) can both induce and suppress cellular immunity; the IL-12 p40 subunit is also a component of IL-23, which can promote tumor growth. IL-12 plasma levels have been reported to rise with age. Since survival in melanoma patients also depends on age, we investigated the relationship between IL-12, age and survival in a large cohort of melanoma patients. Methods: Melanoma patients underwent blood draw for determination of combined IL-12-p40 levels by ELISA. Clinical data was obtained from a prospective database. AJCC stage of disease, age and overall survival (OS) were determined from the date of blood draw. Results: Plasma IL-12 levels were determined in 658 patients (445 stages I-II, 150 stage III, 63 stage IV). IL-12 levels rose with age, with mean levels of 75, 84, 96 and 112 pg/ml in ages 150 pg/ml) was >4-fold greater than that of patients with normal IL-12. Furthermore, the association of elevated IL-12 with OS in stage III patients was independent of the extent of regional disease. Conclusions: An elevated plasma level of IL-12 is an independent predictor of poor prognosis in melanoma patients with regional metastasis. The association between IL-12 and advanced age could help explain the link between age and poorer prognosis in melanoma. Elevated IL-12 may be a marker of an immunosuppressive, tumor-promoting response in melanoma patients. Prognostic factorUnivariate PMultivariate PHazard ratio (95% CI)Gender (M v. F)0.461--Age (yr)0.0300.349-Extent of disease (stage III A v. B v. C)0.0310.031Elevated IL-12 (> 150 pg/ml)0.0010.0044.763 (1.660-13.669)

8504 Background: EORTC 18991 is the largest adjuvant trial ever conducted in stage III melanoma. It assessed the efficacy and toxicity of long term PEG-IFN vs Observation (Obs.). Methods: PEG-IFN (Induction at 6μg/Kg/wk, sc, 8 weeks; followed by Maintenance at 3μg/Kg/wk, sc) for a total treatment duration of 5 years was compared to Obs. in 1256 patients (pts) with stage III melanoma (anyTN1–2M0 without in-transit metastases). Randomization was stratified for nodal involvement N1 (microscopic) vs N2 (palpable nodes), # of nodes, Breslow and ulceration of primary, sex and center. Distant Metastasis-Free Survival (DMFS) was the primary endpoint. Relapse-Free Survival (RFS) was the pre-specified regulatory primary endpoint. Overall survival (OS) was the secondary endpoint. Intent-to-treat analysis was performed. Results: Median follow-up was 3.8 yrs: HR = Hazard Ratio; NR = Not Reached In N1-pts (n=543) the benefit of PEG-IFN seemed more pronounced than in N2-pts (n=713): RFS (HR 0.73 p=0.02 and HR 0.86 p=0.12 for N1 and N2, respectively), DMFS (HR 0.75 p=0.03 and HR 0.94 p=0.53) and OS (HR 0.88 p=0.43 and HR 1.01 p=0.91). PEG-IFN therapy relative dose intensity (actual/planned dose while treated) reached median 88% (induction) and 83% (maintenance). 251 pts (40 %) stopped PEG-IFN because of toxicity. Grade 3–4 - mostly grade 3 - toxicities were reported in 45% (PEG-IFN), vs 12% (Obs.), including most frequently fatigue (15%), hepatotoxicity (10%) and depression (6%) with ECOG 0–1 Performance Status maintained in 83% of pts during maintenance. Conclusions: Long term PEG-IFN therapy in stage III melanoma had a significant and sustained impact on RFS, but not on DMFS and OS. Pts with only microscopic nodal involvement (Sentinel Node positive) seemed to have greater benefit in terms of both RFS and DMFS. Similar better effects of adjuvant IFN therapy in pts with lower disease burden are observed in 2 consecutive EORTC trials (18952 and 18991) involving 2644 pts. [Table: see text] [Table: see text]

8518 Background: S100B serum levels have been reported to correlate with tumor stage and outcome, especially in metastatic melanoma. In the EORTC 18952 randomized trial assessing the value of intermediate doses (10 MU or 5 MU) of IFNa vs Observation, a side study on S100B has been set-up in order to assess 1) the prognostic importance of initial measurement of S100B; 2) the risk of developing distant metastases in patients with a S100B≥0.2 μg/l; 3) the prognostic importance of the latest measurement of S100B level on the subsequent outcome. Methods: The serial measurements of S100B, made by immunoluminometric assay LIA-mat (Sangtec Medical, Sweden) have been performed at randomization in 18952 study, at end of 4-week IFNa induction/observation, and thereafter, at month 1, 3, 6, 9, 12, 16, 20, 24, 30 and 36. The prognostic impact regarding DMFS of the latest value of S100B was assessed via the Cox time-dependent model. Results: A total of 211 patients, stage IIb (N=51) or stage III (N=160), were randomized in the 18952 study between 1996 and 2000, had their initial serum S100B protein level assessed: in 178 patients (84%) S100B was [Table: see text]

The author discusses how a serious illness forced him to reassess the priorities in his life. After being diagnosed with stage III melanoma, he found the comfort and support of friends and colleagues indispensable to helping him cope. During this time he came to realize a need to ease up on professional responsibilities and take more time to enjoy the simple pleasures of life. Key to his experience was embracing the wisdom of letting things go, of consciously making decisions that contribute to more balance in his life.

8020 Background: Recent revisions in the AJCC staging system have increased its complexity without comparable improvement in prognostic accuracy for patients with Stage III melanoma. Furthermore, there remains significant prognostic heterogeneity, even within Stages IIIA, IIIB, and IIIC. The current study was undertaken to develop a model for individual patient risk assessment, both to facilitate patient care, and to help define prognostically homogeneous patient populations for entry into clinical trials. Methods: Patients with AJCC Stage III melanoma were identified from a prospective single institution database. Overall survival was calculated from the date of Stage III to last followup. A multivariate Cox model of independent prognostic factors was developed, and a multivariable individualized patient risk assessment nomogram was built from that model. Results: Among 1,064 patients with Stage III melanoma, 535 have died, at a median followup of 44 months. Independent predictors of overall survival are shown in the table. Individual patient three and five year survival was predicted by incorporating all eight variables into a prognostic nomogram. The nomogram was superior to the AJCC Staging system in predicting outcome in Stage III melanoma patients. Conclusions: Individual patient risk assessment is more accurate than traditional AJCC staging in predicting outcome in Stage III melanoma. This approach, which can be easily incorporated into a handheld computing environment, offers potential advantages for both patient care and clinical research, and should be explored in the next iteration of the AJCC staging system. [Table: see text] No significant financial relationships to disclose.

7568 Background: Data from randomized clinical trials consistently demonstrate that adjuvant HD-IFN in stage III melanoma patients (pts) is associated with approximamate 10% improvement in relapse-...

Lymphocytes from 16 stage I, 6 stage II and 31 stage III melanoma patients (MP) and 51 healthy donors (HD) were tested as far as possible in parallel on a melanoma cell line (NKI-4), a bladder carcinoma cell line (T 24) and 18 different short-term melanoma cultures. Lymphocytes from MP and HD showed cytotoxic effects towards all three types of target cells. Lymphocytes from HD showed the strongest "spontaneous" cytotoxic effects on NKI-4 cells whereas, in general, weak cytotoxic effects were seen on short-term cultured melanoma cells. Within the different lymphocyte donor groups an enormous variation in cytotoxic effects was observed. However, the overall cytotoxic effects of stage I and II MP were significantly higher than those of the HD-group. Stage I MP showed significantly stronger cytotoxic effects on NKI-4 cells than on T 24 cells, indicating that tumour-associated lymphocyte cytotoxicity was superimposed on spontaneous cytotoxicity.

We report clinical and ultrastructural results in eight patients with melanoma and widespread leukoderma. Leukoderma appears to be a good prognostic sign. Although some features of this entity are suggestive of vitiligo, the patients' age, the distribution and appearance of body lesions, and ultrastructural results show a more varied clinical and ultrastructural spectrum. The high frequency of ocular pigmentary disturbances and uveitis in this patient population is noteworthy and deserves further study. We would recommend routine use of Wood's light examination in following patients with thick stage I, stage II, or stage III melanoma to facilitate detection of this phenomenon.

e20103 Background: A large proportion of stage III melanoma patients will develop recurrent and metastatic disease. For these patients, treatment options are still limited. Significant progress has...