Ami Patel

Tumor-Infiltrating Lymphocytes Predict Sentinel Lymph Node Positivity in Patients With Cutaneous Melanoma

PURPOSE Tumor-infiltrating lymphocytes (TILs) are considered a manifestation of the host immune response to tumor, but the influence of TILs on outcome remains controversial. Studies evaluating the prognostic significance of TILs were published before routine examination of draining lymph nodes by sentinel lymph node (SLN) biopsy, the most important predictor of survival in patients with melanoma. The prognostic implications of TILs were re-evaluated in a large group of patients undergoing SLN biopsy at our institution. PATIENTS AND METHODS All patients who underwent SLN mapping for primary cutaneous melanoma between January 1996 and July 2005 were evaluated. Univariate and multivariate analyses were performed to assess factors that predict SLN positivity and survival. Factors analyzed included Breslow thickness, ulceration, anatomic site, sex, Clark level, age, mitotic rate, and the presence (brisk or nonbrisk) or absence of TIL. RESULTS Eight hundred eighty-seven patients underwent SLN mapping, and a SLN was identified in 875 patients (98.8%). The SLN was positive for tumor in 156 patients (17.6%). Multivariate analysis revealed that only Breslow thickness (P < .0001), ulceration (P = .0004), male sex (P = .03), and absent TILs (P = .0003) were independently predictive of the presence of SLN metastases. In melanomas with a brisk TIL infiltrate, the probability of a positive SLN was 3.9% as compared with 26.2% for melanomas in which TILs were absent. TILs were not an independent predictive factor for survival. CONCLUSION The absence of TILs, together with increasing Breslow thickness, presence of ulceration and male sex, predicts SLN metastasis in patients undergoing SLN biopsy for primary cutaneous melanoma.

Variates of Survival in Metastatic Uveal Melanoma

PURPOSE The course and outcome of metastatic uveal melanoma are not well described. We evaluated the survival of our patients with metastatic uveal melanoma, described factors that correlated with survival, and evaluated the influence of screening tests on time of detection and survival. PATIENTS AND METHODS All patients with metastatic uveal melanoma seen at Memorial Sloan-Kettering Cancer Center between 1994 and 2004 were identified from our database. We recorded date of initial diagnosis, date of metastatic disease, date of last follow-up, site of the first metastasis, how the first metastasis was discovered, treatment, and outcome of therapy. RESULTS The estimated median survival of the 119 patients analyzed was 12.5 months; 22% of patients were alive at 4 years. Five variates correlated independently with prolonged survival: Lung/soft tissue as only site of first metastasis, treatment with surgery or intrahepatic therapy, female sex, age younger than 60, and a longer interval from initial diagnosis to metastatic disease. Discovering metastatic disease in asymptomatic patients did not correlate with overall survival; 89% of patients had a single organ as the site of first metastasis. Although liver was the most common site, 39.5% of patients had nonliver sites, most commonly lung, as the first site of metastasis. CONCLUSION A substantial subset of patients with metastatic uveal melanoma survive more than 4 years with metastatic disease. Data on variates of survival and site of first metastasis may guide strategies for screening patients, although our data failed to show a survival advantage in discovering asymptomatic metastatic disease.

A phase II trial of isolated limb infusion with melphalan and dactinomycin for regional melanoma and soft tissue sarcoma of the extremity

BackgroundIsolated limb infusion (ILI) is a minimally invasive technique of delivering regional chemotherapy in patients with advanced melanoma or soft tissue sarcoma of the limb. Reports from Australia of efficacy similar to that of isolated limb perfusion prompted us to conduct a phase II trial to evaluate the efficacy and safety of ILI.MethodsEligible patients had American Joint Committee on Cancer stage IIIB or IIIC melanoma or unresectable soft tissue sarcoma of the limb. Angiographic catheters were positioned just above the knee or elbow of the extremity. General anesthesia was performed, a proximal tourniquet was inflated, and a normothermic, low-flow, hypoxic infusion of melphalan and dactinomycin was circulated through the involved limb for 20 minutes. The tumor response was assessed by using standard criteria at 3 months. Morbidity was determined in the hospital and at 2, 6, and 12 weeks.ResultsTwenty-five patients were accrued to the trial, and 32 ILIs were performed (8 patients had 2 ILIs); 1 patient was not treated. Of the 22 assessable patients, 11 (50%) had a significant response at 3 months: 23% of patients had a complete response, and 27% of patients had a partial response. The median duration of complete response was 1 year (range, 6–32 months). Morbidity was acceptable. Peak morbidity occurred at 2 weeks and was considered moderate in most patients. Limb edema and erythema were common. No patient developed compartment syndrome or required amputation.ConclusionsILI is well tolerated. Half of the patients experienced a complete or partial response.

Utility of Preoperative [(18)]F Fluorodeoxyglucose–Positron Emission Tomography Scanning in High-Risk Melanoma Patients

Background[(18)]F Fluorodeoxyglucose-positron emission tomography (PET) scanning provides functional imaging based on glucose uptake by tumors. Melanoma is a glucose-avid malignancy, and preoperative PET scanning in melanoma patients has the potential to guide appropriate treatment.MethodsWe performed a prospective trial to evaluate the clinical utility of whole-body fluorine 18–labeled deoxyglucose-PET scanning used in addition to standard imaging (contrast-enhanced computed tomographic [CT] imaging of the chest, abdomen, and pelvis) in preoperative stage IIC (T4N0M0), III (any T, N1 to N3, M0), and IV (any T, any N, M1) melanoma patients. Pathologic or clinical follow-up within 4 to 6 months of the imaging studies was used to determine the accuracy of preoperative PET and CT scan findings.ResultsPreoperative imaging findings led to a change in clinical management in 36 (35%) of 103 patients. In 32 (89%) of these patients, the information was accurate. Findings on PET scan alone (14 of 36; 39%) or in combination with CT (20 of 36; 56%) resulted in a treatment change in most patients (34 of 36; 94%). The most common decision was to cancel the operation (19 of 36; 53%). PET scanning was more sensitive than CT scanning in detecting occult disease (68% vs. 48%; P = .05), but both tests were highly specific (92% vs. 95%; P = .7, PET vs. CT).ConclusionsPET scanning facilitates the appropriate management of high-risk melanoma patients being considered for operative intervention. PET imaging in addition to CT scanning should be strongly considered before operation in patients at high risk for occult metastatic disease.

Stage-IV Melanoma and Pulmonary Metastases: Factors Predictive of Survival

BackgroundWe reviewed a contemporary, single-institution experience to evaluate the natural history of stage-IV melanoma metastatic to the lung and identify factors predictive of survival.MethodsA search of our prospective database was performed to identify patients with stage-IV melanoma and pulmonary metastases as the initial disease site; only patients seen at our institution prior to developing stage-IV disease and in whom treatment response was available were included. Patients’ demographic, clinical, and treatment variables were recorded. Cox regression was used to identify factors independently predictive of survival.ResultsThe study cohort was comprised of 122 patients. Median survival was 14 months (5-year survival of 8%). Clinical factors at time of diagnosis of stage IV independently predictive of survival were a solitary pulmonary metastasis (HR 2.7, CI 1.6–4.4, P<0.0005) and absence of extra-pulmonary disease (HR 1.9, CI 1.2–3.1, P = 0.01). Among treatment factors, only metastasectomy was independently predictive of survival (HR 0.42, CI 0.21–0.87, P = 0.02). Of the patients, 26 (21%) underwent metastasectomy, with a median survival of 40 months compared with 13 months in patients not selected for surgical treatment. Of these 26, 23 (88%) experienced recurrence at a median of 5 months after the procedure. No survival difference was seen between responders and non-responders to systemic therapy (P = 0.55).ConclusionsIn stage-IV melanoma with pulmonary metastases, a solitary metastasis and absence of extra-pulmonary disease are predictive of survival. While these factors are often present in patients selected for pulmonary metastasectomy, this independently predicts survival. However, response to systemic therapy does not correlate with a survival difference.

Matrix Metalloproteinase-9 ( MMP-9 ) polymorphisms in patients with cutaneous malignant melanoma

BackgroundCutaneous Malignant Melanoma causes over 75% of skin cancer-related deaths, and it is clear that many factors may contribute to the outcome. Matrix Metalloproteinases (MMPs) play an important role in the degradation and remodeling of the extracellular matrix and basement membrane that, in turn, modulate cell division, migration and angiogenesis. Some polymorphisms are known to influence gene expression, protein activity, stability, and interactions, and they were shown to be associated with certain tumor phenotypes and cancer risk.MethodsWe tested seven polymorphisms within the MMP-9 gene in 1002 patients with melanoma in order to evaluate germline genetic variants and their association with progression and known risk factors of melanoma. The polymorphisms were selected based on previously published reports and their known or potential functional relevance using in-silico methods. Germline DNA was then genotyped using pyrosequencing, melting temperature profiles, heteroduplex analysis, and fragment size analysis.ResultsWe found that reference alleles were present in higher frequency in patients who tend to sunburn, have family history of melanoma, higher melanoma stage, intransit metastasis and desmoplastic melanomas among others. However, after adjustment for age, sex, phenotypic index, moles, and freckles only Q279R, P574R and R668Q had significant associations with intransit metastasis, propensity to tan/sunburn and primary melanoma site.ConclusionThis study does not provide strong evidence for further investigation into the role of the MMP-9 SNPs in melanoma progression.

Patterns of first-recurrence and post-recurrence survival in patients with primary cutaneous melanoma after sentinel lymph node biopsy.

BackgroundSentinel lymph node biopsy (SLNB) has become well accepted in management of patients with primary cutaneous melanoma. An understanding of the pattern of recurrence after SLNB is helpful in coordinating a rational plan of follow-up in these patients. We sought to determine the site and timing of initial recurrence and post-recurrence survival after SLNB.MethodsStage I/II melanoma patients who underwent SLNB during 1991–2004 were identified from a prospective single-institution database. Site and date of first recurrence after SLNB were recorded. Patterns of recurrence after SLNB and post-recurrence survival were analyzed.ResultsOne thousand and forty-six patients underwent SLNB. The sentinel lymph node (SLN) was positive in 164 patients (16%). Median follow-up was 36 months for survivors. Median and 3-year relapse-free survival for SLN-positive patients were 41 months and 56%, and for SLN-negative patients were not reached and 87%, respectively (P < .0001). Of the SLN-positive patients, 47% experienced recurrence, compared with 14% SLN-negative patients. The pattern of recurrence stratified by SLN status was similar between the two groups (P = NS). After recurrence, the site of recurrence was the only significant prognostic factor influencing survival (P < .0001).ConclusionsAlthough SLN-positive patients experience recurrence far earlier and more frequently than SLN-negative patients, the pattern of recurrence is similar. After recurrence, its site is the primary determinant of survival.

Estimates of stage-specific survival are altered by changes in the 2002 American Joint Committee on Cancer staging system for melanoma.

The objectives of the current study were to examine how the estimated stage‐specific survival is altered in the 2002 American Joint Committee on Cancer (AJCC) melanoma staging system compared with the 1997 AJCC staging system and to contrast the predictive accuracy of the 2 staging systems.

Isolated limb infusion with melphalan and dactinomycin for regional melanoma and soft-tissue sarcoma of the extremity: final report of a phase II clinical trial.

Isolated limb infusion (ILI) is a minimally invasive technique of delivering regional chemotherapy in patients with advanced melanoma or soft-tissue sarcoma of the limb. We report the final results of the first clinical trial of ILI in North America (NCT00004250). Eligible patients had recurrent melanoma or unresectable soft-tissue sarcoma of the limb. Angiographic catheters were positioned just above the knee or elbow of the extremity. General anesthesia was performed, a proximal tourniquet inflated, and a normothermic, low flow, hypoxic infusion of melphalan and dactinomycin circulated through the involved limb for 20 min. Tumor response and morbidity were assessed using standard criteria. Thirty-seven patients were accrued to the trial and 44 ILIs were performed (eight patients had two ILIs); one patient was not treated. Of the 32 evaluable patients, 17 (53%) had a significant response at 3 months: 25% of patients had a complete response and 28% of patients had a partial response. The median duration of complete response was 1 year (5–32 months). Morbidity was acceptable, with peak erythema, edema, and pain experienced at 2 weeks and considered ‘moderate’ in most patients. No patients developed compartment syndrome or required amputation because of ILI. ILI is well tolerated. More than half of the treated patients experienced a complete or partial response.

Variates of survival for stage IV uveal melanoma

7536 Background: Systemic therapy of stage IV uveal melanoma (mel) is not thought to improve survival. In selected patients (pts), local therapy of metastases (mets) (e.g. surgery or intrahepatic therapy) can be associated with long-term survival. The natural history of stage IV mel is heterogeneous and not well-described. We were interested in describing the natural history and factors that correlate with long-term survival in the stage IV uveal mel pts seen at our institution. Methods: A retrospective analysis of the 119 stage IV uveal mel pts in the MSKCC mel database. We recorded dates of initial diagnosis, stage IV, last follow up, and death; site of 1st met, how the 1st met was discovered, treatment. Results: 40 pts were still alive at last follow up (median follow up of survivors = 8 months). Median overall survival was 12.5 months (95% CI 9.6–16.8). 22% were alive at 4 years. A novel observation was that 28% of the pts had lung/soft tissue only as the site of first metastasis. In a multivariate an...