Current management of melanoma patients with nodal metastases.

The management of melanoma patients with nodal metastases has undergone dramatic changes over the last decade. In the past, the standard of care for patients with a positive sentinel lymph node biopsy (SLNB) was a completion lymph node dissection (CLND), while patients with palpable macroscopic nodal disease underwent a therapeutic lymphadenectomy in cases with no evidence of systemic spread. However, studies have shown that SLN metastases present as a spectrum of disease, with certain SLN-based factors being prognostic of and correlated with outcomes.

Preoperative Ultrasound Assessment of Regional Lymph Nodes in Melanoma Patients Does not Provide Reliable Nodal Staging: Results From a Large Multicenter Trial.

Objective: To assess whether preoperative ultrasound (US) assessment of regional lymph nodes in patients who present with primary cutaneous melanoma provides accurate staging.

Background: It has been suggested that preoperative US could avoid the need for sentinel node (SN) biopsy, but in most single-institution reports, the sensitivity of preoperative US has been low.

Methods: Preoperative US data and SNB results were analyzed for patients enrolled at 20 centers participating in the screening phase of the second Multicenter Selective Lymphadenectomy Trial.

Lymph node metastasis in melanoma: a debate on the significance of nodal metastases, conditional survival analysis and clinical trials.

While there is no doubt that regional lymph node metastases are an enormously important factor in melanoma staging and treatment, the biology behind this significance and its precise implications for treatment planning have been a leading controversy in melanoma and other solid tumors for over a century. Recent clinical data, including data from prospective randomized clinical trials have refined our understanding of the process of nodal metastases and the advantages and disadvantages of different clinical management strategies. This review presents two points of view in this debate and discusses the results of new data analyses as well as pivotal clinical trials informing the discussion.

Phase III Randomized Study of 4 Weeks of High-Dose Interferon-α-2b in Stage T2bNO, T3a-bNO, T4a-bNO, and T1-4N1a-2a (microscopic) Melanoma: A Trial of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group (E1697).

Purpose To test the efficacy of 4 weeks of intravenous (IV) induction with high-dose interferon (IFN) as part of the Eastern Cooperative Oncology Group regimen compared with observation (OBS) in patients with surgically resected intermediate-risk melanoma. Patients and Methods In this intergroup international trial, eligible patients had surgically resected cutaneous melanoma in the following categories: (1) T2bN0, (2) T3a-bN0, (3) T4a-bN0, and (4) T1-4N1a-2a (microscopic). Patients were randomly assigned to receive IFN α-2b at 20 MU/m/d IV for 5 days (Monday to Friday) every week for 4 weeks (IFN) or OBS.

Localization Methods for Excisional Biopsy in Women With Nonpalpable Mammographic Abnormalities.

Introduction: With the advent and proliferation of breast cancer screening programs, more women are being diagnosed with mammographic abnormalities that require tissue diagnosis. If imaged-guided biopsy is not possible or previous image-guided biopsies reveal pathologies that require more extensive surgery, guided excisional biopsy/lumpectomy may be necessary.

Methods: Fifteen women were enrolled in the study of the feasibility of off-site or day-before wire-localization excisional biopsy of the breast with mammographic abnormalities.

Breast Lymphatic Mapping and Sentinel Lymph Node Biopsy: State of the Art: 2015.

Lymphatic mapping with sentinel lymph node biopsy (SLNB) was introduced in the 1990s as a method to stage the nodal axilla in women with breast cancer. Very quickly the technique became the standard of care because pathologic staging was more accurate and sensitive and the surgical procedure resulted in low morbidity. SLNB has continued to evolve, and the applications in breast cancer have been expanded.

Final Results of the Sunbelt Melanoma Trial: A Multi-Institutional Prospective Randomized Phase III Study Evaluating the Role of Adjuvant High-Dose Interferon Alfa-2b and Completion Lymph Node Dissection for Patients Staged by Sentinel Lymph Node Biopsy.

Purpose: The Sunbelt Melanoma Trial is a prospective randomized trial evaluating the role of high-dose interferon alfa-2b therapy (HDI) or completion lymph node dissection (CLND) for patients with melanoma staged by sentinel lymph node (SLN) biopsy.

Patients And Methods: Patients were eligible if they were age 18 to 70 years with primary cutaneous melanoma ≥ 1.0 mm Breslow thickness and underwent SLN biopsy.

Comparison of sentinel lymph node micrometastatic tumor burden measurements in melanoma.

Background: Multiple methods have been proposed to classify the micrometastatic tumor burden in sentinel lymph nodes (SLN) for melanoma. The purpose of this study was to determine the classification scheme that best predicts nonsentinel node (NSN) metastasis, disease-free survival (DFS), and overall survival (OS).

Study Design: A single reviewer reanalyzed tumor-positive SLN from a multicenter, prospective clinical trial of patients with melanoma ≥ 1.

Diversity of stage III melanoma in the era of sentinel lymph node biopsy.

Background: Sentinel lymph node (SLN) biopsy for melanoma often detects minimal nodal tumor burden. Although all node-positive patients are considered stage III, there is controversy regarding the necessity of adjuvant therapy for all patients with tumor-positive SLN.

Methods: Post hoc analysis was performed of a prospective multi-institutional study of patients with melanoma ≥ 1.

Evidence for a better nodal staging system for melanoma: the clinical relevance of metastatic disease confined to the sentinel lymph nodes.

Background: The hypothesis tested in this study was whether patients with stage III metastatic melanoma confined to their sentinel lymph nodes (SLNs) had a more favorable prognosis than patients who had SLN and non-SLN (NSLN) metastases.

Methods: Patients were identified who were clinically negative in their regional basins but with lymphatic mapping were found to have positive SLNs (331 patients). All patients subsequently underwent a complete lymph node dissection of the lymphatic basin involved, and the total number of metastatic SLNs and NSLNs were documented.

Metastasectomy for distant metastatic melanoma: analysis of data from the first Multicenter Selective Lymphadenectomy Trial (MSLT-I).

Background: For stage IV melanoma, systemic medical therapy (SMT) is used most frequently; surgery is considered an adjunct in selected patients. We retrospectively compared survival after surgery with or without SMT versus SMT alone for melanoma patients developing distant metastases while enrolled in the first Multicenter Selective Lymphadenectomy Trial.

Methods: Patients were randomized to wide excision and sentinel node biopsy, or wide excision and nodal observation.

gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma.

Background: Stimulating an immune response against cancer with the use of vaccines remains a challenge. We hypothesized that combining a melanoma vaccine with interleukin-2, an immune activating agent, could improve outcomes. In a previous phase 2 study, patients with metastatic melanoma receiving high-dose interleukin-2 plus the gp100:209-217(210M) peptide vaccine had a higher rate of response than the rate that is expected among patients who are treated with interleukin-2 alone.

A phase 2 study of tasisulam sodium (LY573636 sodium) as second-line treatment for patients with unresectable or metastatic melanoma.

Background: Tasisulam sodium (hereafter, tasisulam) is a novel anticancer agent that induces apoptosis through the intrinsic pathway and has antiangiogenic activity in preclinical models. Tasisulam demonstrated activity across a broad range of tumors, including melanoma. The primary objective of this phase 2 study was to determine the objective response rate (ORR) in patients who had received 1 previous systemic chemotherapy for unresectable/metastatic melanoma; secondary objectives were to evaluate the clinical response rate (CRR), progression-free survival (PFS), overall survival (OS), duration of response, safety, and pharmacokinetics.

Ulceration as a predictive marker for response to adjuvant interferon therapy in melanoma.

Objective: This analysis was performed to investigate the hypothesis that ulceration predicts improved response to adjuvant interferon (IFN) therapy.

Summary Background Data: Several studies have demonstrated that adjuvant therapy for high-risk melanoma patients with IFN alfa-2b improves disease-free survival (DFS), although the impact on overall survival (OS) is controversial. Recent data have suggested that IFN therapy may preferentially benefit patients with ulcerated primary melanomas.

Second primary melanomas: incidence and outcome.

The objective of this study was to determine the incidence of multiple primary melanomas (MPM) and other cancers types among patients with melanoma. Factors associated with development of MPM were assessed in a post hoc analysis of the database from a multi-institutional prospective randomized trial of patients with melanoma aged 18 to 70 years with Breslow thickness 1 mm or greater. Disease-free survival (DFS) and overall survival (OS) were evaluated by Kaplan-Meier analysis.

The prognostic significance of nonsentinel lymph node metastasis in melanoma.

Background: We hypothesized that metastasis beyond the sentinel lymph nodes (SLN) to the nonsentinel nodes (NSN) is an important predictor of survival.

Materials And Methods: Analysis was performed of a prospective multi-institutional study that included patients with melanoma ≥ 1.0 mm in Breslow thickness.

Prognostic information from sentinel lymph node biopsy in patients with thick melanoma.

Hypothesis: Sentinel lymph node (SLN) biopsy provides valuable prognostic information for patients with thick (T4) melanoma.

Design: Post hoc analysis of data from a prospective, randomized trial.

Setting: Academic and private hospitals.

The impact on morbidity and length of stay of early versus delayed complete lymphadenectomy in melanoma: results of the Multicenter Selective Lymphadenectomy Trial (I).

Background: Complete lymph node dissection, the current standard treatment for nodal metastasis in melanoma, carries the risk of significant morbidity. Clinically apparent nodal tumor is likely to impact both preoperative lymphatic function and extent of soft tissue dissection required to clear the basin. We hypothesized that early dissection would be associated with less morbidity than delayed dissection at the time of clinical recurrence.

Advances in local-regional treatment for patients with early-stage breast cancer: a review of the field.

This review highlights advances in the field of the local-regional treatment for patients with early-stage breast cancer. Through the years, the surgical treatment for early-stage breast cancer has evolved into more conservative treatment, with breast-conserving measures replacing the mastectomy as the most common procedure performed to treat the primary tumor. Likewise, nodal staging has evolved so that the lymphatic mapping procedures have replaced axillary dissection, resulting in a less morbid procedure and better staging information.

The changing face of malignant melanoma.

Background And Objectives: There is currently an epidemic of malignant melanoma occurring in the United States. At the same time there has been a heightened awareness for early detection of melanoma in the professional ranks as well as in the lay population. A database review was performed to investigate the changing patterns of melanoma presentation during a 2 decade time period in the State of Florida.

Adherence to the National Quality Forum (NQF) breast cancer measures within cancer clinical trials: a review from ACOSOG Z0010.

Background: In 2007, the National Quality Forum (NQF) released four performance measures for the treatment of breast cancer. We proposed to study the degree of adherence with these measures among participating institutions in a multi-institutional trial.

Methods: American College of Surgeons Oncology Group (ACOSOG) Z0010 enrolled breast cancer patients onto a phase II trial studying the prognostic significance of bone marrow and sentinel node micrometastases.