Integrating 31-Gene Expression Profiling With Clinicopathologic Features to Optimize Cutaneous Melanoma Sentinel Lymph Node Metastasis Prediction.

National guidelines recommend sentinel lymph node biopsy (SLNB) be offered to patients with > 10% likelihood of sentinel lymph node (SLN) positivity. On the other hand, guidelines do not recommend SLNB for patients with T1a tumors without high-risk features who have < 5% likelihood of a positive SLN. However, the decision to perform SLNB is less certain for patients with higher-risk T1 melanomas in which a positive node is expected 5%-10% of the time. We hypothesized that integrating clinicopathologic features with the 31-gene expression profile (31-GEP) score using advanced artificial intelligence techniques would provide more precise SLN risk prediction. METHODS: An integrated 31-GEP (i31-GEP) neural network algorithm incorporating clinicopathologic features with the continuous 31-GEP score was developed using a previously reported patient cohort (n = 1,398) and validated using an independent cohort (n = 1,674). RESULTS: Compared with other covariates in the i31-GEP, the continuous 31-GEP score had the largest likelihood ratio (G2 = 91.3, P < .001) for predicting SLN positivity. The i31-GEP demonstrated high concordance between predicted and observed SLN positivity rates (linear regression slope = 0.999). The i31-GEP increased the percentage of patients with T1-T4 tumors predicted to have < 5% SLN-positive likelihood from 8.5% to 27.7% with a negative predictive value of 98%. Importantly, for patients with T1 tumors originally classified with a likelihood of SLN positivity of 5%-10%, the i31-GEP reclassified 63% of cases as having < 5% or > 10% likelihood of positive SLN, for a more precise, personalized, and clinically actionable SLN-positive likelihood estimate. CONCLUSION: These data suggest the i31-GEP could reduce the number of SLNBs performed by identifying patients with likelihood under the 5% threshold for performance of SLNB and improve the yield of positive SLNBs by identifying patients more likely to have a positive SLNB.

Outcomes for lymph node-positive cutaneous melanoma over two decades.

BACKGROUND: Our aim was to demonstrate that, despite advances in treatment and surveillance of node-positive cutaneous melanoma, rates of overall survival (OS) and melanoma-specific survival (MSS) have not changed over the last two decades. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute to identify patients with node-positive cutaneous melanoma. Patients were categorized by treatment era; the first era encompassed patients diagnosed from 1988 to 1999 and the second era 2000 to 2006. Multivariate Cox proportional hazards models compared rates of OS and MSS between treatment eras while controlling for known prognostic factors. We reported risks of death as hazard ratios (HR) with 95% confidence intervals (CI) and set significance at P≤0.05. RESULTS: Entrance criteria were met by 6,868 patients, 1,631 (23.8%) treated in era I and 5,237 (76.3%) treated in era II. On multivariate analysis, era II patients did not demonstrate a significantly different risk of death from any cause (HR 0.89, CI 0.79-1.01; P<0.08), but they did have a lower risk of melanoma-specific mortality (HR 0.81, CI 0.71-0.93; P=0.003) relative to their era I counterparts. CONCLUSIONS: Over nearly two decades, MSS but not OS has improved for AJCC stage III melanoma patients. Stage migration is likely responsible for any improvement in MSS among patients in the most recently diagnosed era.

A rational surgical approach to the treatment of distant melanoma metastases.

The optimal treatment of melanoma involves multidisciplinary care. To many, this means surgical resection of early, localized disease and treatment of metastatic disease with chemotherapy, immunotherapy, or radiation. Because it is effective, results in little morbidity and may be repeated, surgery should have a central role in the treatment of selected patients with American Joint Committee on Cancer (AJCC) stage IV melanoma.

The role of surgery in treatment of stage IV melanoma.

The prognosis for patients with melanoma has not improved over the last 30 years. So far, almost without exception, clinical trials conducted with single or multiple agent chemotherapy, biological therapy (interferon-alpha, interleukin-2), and biochemotherapy have failed to demonstrate consistent survival benefit. Without effective alternate treatments, surgery must be considered the primary treatment of melanoma, independent of disease stage. Although surgery is clearly favored as the treatment of localized melanoma, consensus opinion and clinician preference become divided once melanoma progresses beyond its primary site. Many physicians will adopt an attitude of resignation and hesitancy when treating metastatic melanoma. As a result, patients with advanced disease are often treated with medications that produce little survival or palliative benefit at the expense of significant toxicity. Numerous studies have demonstrated clear and durable survival advantages for patients undergoing complete resection of metastatic melanoma. Further, surgical resection can produce an immediate decrease in tumor burden with minimal morbidity and mortality at a reasonable cost.

Can surgical therapy alone achieve long-term cure of melanoma metastatic to regional nodes?

BACKGROUND: Anecdotal reports of melanoma recurrence 15 years after complete lymphadenectomy have led to claims that the onset of nodal metastasis invariably signals systemic metastases and a terminal diagnosis. Few series in the literature are able to refute this assertion. We therefore examined rates of long-term (> 15-25 years) survival for patients with regional (nodal) melanoma. PATIENTS AND METHODS: We performed an analysis of patients with American Joint Committee on Cancer stage III melanoma entered into a prospective database for the last 30 years. All patients were seen at the treating institution within 4 months of their diagnosis and monitored thereafter. All patients underwent complete lymphadenectomy. Patients receiving melanoma vaccines were excluded. Statistical comparisons used Chi-square analysis and the log-rank test. RESULTS: At a maximum follow up of 386 months (32 years) for the population of 1422 patients, rates of 15-, 20-, and 25-year melanoma-specific survival were 36% +/- 1%, 35% +/- 1%, and 35% +/- 1%, respectively. When patients were stratified by clinical status of regional lymph nodes, survival rates were significantly lower (P = 0.001) if nodes were palpable. The number of tumor-positive nodes (P < 0.0001), the pathological primary tumor stage (P = 0.005), age (P = 0.0001), and gender (P = 0.002) also were significantly related to long-term survival. DISCUSSION: Long-term survivors of melanoma metastatic to regional lymph nodes are not uncommon, and the extremely low rate of recurrence beyond 15 years suggests that this disease-free interval is usually synonymous with cure. Although some risk factors decrease the likelihood of long-term survival, the high overall rates of extended survival in all risk groups clearly support surgical management as the primary treatment for regional metastatic melanoma.

Colorectal cancer screening and surveillance: current standards and future trends.

Its prevalence, long premalignant course, and favorable response to early intervention make colorectal cancer an ideal target for screening regimens. The success of these regimens depends on accurate assessment of risk factors, patient compliance with scheduled visits and tests, and physician knowledge of screening strategies. We review the current recommendations for colorectal cancer screening in general and at-risk populations, comment on surveillance methods in high-risk patients, and examine current trends that will likely influence screening regimens in the future.

The utility of estrogen receptor, progesterone receptor, and Her-2/neu status to predict survival in patients undergoing hepatic resection for breast cancer metastases.

BACKGROUND: Hepatic metastases from breast cancer signal a dismal prognosis, with a median survival of 9.5 months. METHODS: Twenty breast cancer patients with liver metastases underwent hepatic resection, biopsy, or ablation between 1995 and 2004. Hormone receptor status and Her-2/neu expression of primary and metastatic tumors were correlated with overall survival. RESULTS: At a mean follow-up of 39 months after hepatic resection, median survival was 32 months. Patients undergoing anatomic resection with or without ablation lived significantly longer than those undergoing more limited resections (46 vs. 25 months, P = .016). Survival was significantly greater in patients with estrogen receptor (ER)-positive primary (P = .02) and metastatic (P < .004) tumors, Her-2/neu-positive metastases (P = .02), 50 years at metastasectomy (P = .02). CONCLUSIONS: The ER status of the primary tumor and ER and Her-2/neu status of hepatic metastases, in addition to other clinical factors, may help select patients who would benefit from hepatic metastasectomy.