ABSTRACT
BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. RESULTS: Immediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in the per-protocol analysis. In the per-protocol analysis, the mean (±SE) 3-year rate of melanoma-specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively; P=0.42 by the log-rank test) at a median follow-up of 43 months. The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively; P=0.05 by the log-rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%; P<0.001 by the log-rank test); these results must be interpreted with caution. Nonsentinel-node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence (hazard ratio, 1.78; P=0.005). Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. CONCLUSIONS: Immediate completion lymph-node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma-specific survival among patients with melanoma and sentinel-node metastases. (Funded by the National Cancer Institute and others; MSLT-II ClinicalTrials.gov number, NCT00297895 .).
Subject(s)
Lymph Node Excision , Melanoma/secondary , Sentinel Lymph Node Biopsy , Sentinel Lymph Node/surgery , Watchful Waiting , Adult , Aged , Disease-Free Survival , Female , Humans , Intention to Treat Analysis , Lymph Node Excision/adverse effects , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Lymphatic Metastasis/diagnosis , Lymphedema/etiology , Male , Melanoma/mortality , Melanoma/pathology , Melanoma/surgery , Middle Aged , Neoplasm Staging/methods , Postoperative Complications , Prognosis , Proportional Hazards Models , Sentinel Lymph Node/pathology , Sentinel Lymph Node Biopsy/adverse effects , Survival Analysis , Ultrasonography , Young AdultABSTRACT
The sequencing of the human genome and the ability to rapidly identify genes and proteins, both normal and mutant, that are involved in tumorigenesis and malignant phenotypes, have changed the ability to understand malignant cells. Understanding and applying this information to the diagnosis and treatment of cancer are facilitated best with a multidisciplinary team. The cancer surgeon plays a pivotal role in this team. This article briefly summarizes: (1) the clinically relevant applications of molecular biology to the cancer surgeon, (2) the current understanding of the molecular basis for cancer, and (3) the current targeted agents and their clinical applications.
Subject(s)
Neoplasms/genetics , Neoplasms/therapy , Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , DNA Repair , Disease Progression , Epigenesis, Genetic , Humans , Neoplasms/drug therapy , Neoplastic Stem Cells/drug effects , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Phenotype , Vascular Endothelial Growth Factor A/antagonists & inhibitorsABSTRACT
BACKGROUND: We determined the effect of positron emission tomography (PET) on surgical decision-making in patients with metastatic or recurrent colorectal cancer. METHODS: A total of 114 patients with advanced colorectal cancer were imaged with computed tomography (CT) and PET scans. The PET and CT scans were independently interpreted before surgery and recorded. RESULTS: Forty-two of the 114 patients had resectable disease on the basis of CT. PET altered therapy in 17 (40%) of these 42 patients on the basis of the following results: extrahepatic disease (n = 9), bilobar involvement (n = 3), thoracic involvement (n = 5), retroperitoneal lymphadenopathy (n = 2), bone involvement (n = 1), and supraclavicular disease (n = 1). In 25 patients with liver metastases only, PET found additional disease in 18 (72%), extrahepatic disease in 11, chest disease in 13, retroperitoneal lymphadenopathy in 4, and bone disease in 3. In five patients, both scans underestimated small-volume peritoneal metastases discovered at laparotomy. CONCLUSIONS: PET altered therapy in 40% of patients. In patients with isolated liver involvement, 72% had more extensive disease that precluded surgical resection. PET scans should be used in the management of patients with recurrent colorectal cancer who are being considered for potentially curative surgery.