Jeffrey D. Wayne

Small bowel cancer in the United States: changes in epidemiology, treatment, and survival over the last 20 years.

Background:Previous studies have shown an increasing incidence of small bowel tumors in the United States. Our objective was to assess this increase by examining changes in histology-specific incidence, treatment, and survival. Methods:Patients with small bowel malignancies were identified from the National Cancer Data Base (NCDB, 1985–2005) and the Surveillance Epidemiology and End Results (SEER, 1973–2004) database. Age-adjusted incidence rates were calculated using SEER. Treatment and survival trends over time were examined using the National Cancer Data Base. Regression models were developed to assess survival over time. Results:Sixty-seven thousand eight hundred forty-three patients were identified with small bowel malignancies: 37.4% carcinoid, 36.9% adenocarcinomas, 8.4% stromal tumors, and 17.3% lymphomas. From 1973 to 2004, the incidence of carcinoid tumors increased more than 4-fold (2.1 to 9.3 per million), whereas changes in adenocarcinomas, stromal tumors, and lymphomas were less pronounced. From 1985 to 2005, utilization of surgery increased significantly for carcinoid tumors from 78.8% to 87.4% (P < 0.0001). Adjuvant chemotherapy utilization for adenocarcinoma increased from 8.1% in 1985 to 23.8% in 2005 (P < 0.0001). Treatment over time was generally unchanged for lymphoma and stromal tumors. Five-year survival after resection remained unchanged over time for all histologic subtypes even after adjusting for changes in patient demographics, tumor characteristics, and treatment approaches. Conclusions:The overall incidence of small intestine malignancies has increased considerably, primarily because of carcinoid tumors which are now the most common small bowel cancer. With current treatments, survival has remained relatively unchanged over the last 20 years. Novel therapeutic options need to be investigated.

A multi-institutional phase II trial of preoperative full-dose gemcitabine and concurrent radiation for patients with potentially resectable pancreatic carcinoma

BackgroundWe report the results of a multi-institutional phase II trial that used preoperative full-dose gemcitabine and radiotherapy for patients with potentially resectable pancreatic carcinoma.MethodsPatients were treated before surgery with three cycles of full-dose gemcitabine (1000 mg/m2 intravenously), with radiation during the second cycle (36 Gy in daily 2.4-Gy fractions). Patients underwent surgery 4 to 6 weeks after the last gemcitabine infusion.ResultsThere were 10 men and 10 women, with a median age of 58 years (range, 50–80 years). Nineteen patients (95%) completed therapy without interruption, and one experienced grade 3 gastrointestinal toxicity. The mean weight loss after therapy was 4.0%. Of 20 patients taken to surgery, 17 (85%) underwent resections (16 pancreaticoduodenectomies and 1 distal pancreatectomy). The complication rate was 24%, with an average length of stay of 13.5 days. There were no operative deaths. Pathologic analysis revealed clear margins in 16 (94%) of 17 and uninvolved lymph nodes in 11 (65%) of 17 specimens. One specimen contained no residual tumor, and three specimens revealed only microscopic foci of residual disease. With a median follow-up of 18 months, 7 (41%) of the 17 patients with resected disease are alive with no recurrence, 3 (18%) are alive with distant metastases, and 7 (41%) have died.ConclusionsPreoperative gemcitabine/radiotherapy is well tolerated and safe when delivered in a multi-institutional setting. This protocol had a high rate of subsequent resection, with acceptable morbidity. The high rate of negative margins and uninvolved nodes suggests a significant tumor response. Preliminary survival data are encouraging. This regimen should be considered in future neoadjuvant trials for pancreatic cancer.

Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma

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.)

New therapeutic possibilities in primary invasive breast cancer.

OBJECTIVE Current therapy for small invasive breast cancer, particularly when discovered mammographically, was re-examined. Axillary dissection may be avoided when lymph node metastases incidence is low (< 10%) or when primary cancer features determine adjuvant therapy. Radiation therapy may be avoided when risk of recurrence is very low. SUMMARY BACKGROUND DATA Recent studies by the Surveillance, Epidemiology, and End Results program (SEER) have shown increases in small invasive breast cancers (< 1 cm) attributable to mammographic screening. The incidence of axillary metastases in mammographically discovered small cancers (< 1 cm) may be less than 10%. Follow-up data from the Breast Cancer Detection Demonstration Project (BCDDP) indicate a disease-free survival rate exceeding 95% at 8 years if the cancer was discovered mammographically. METHODS Maximum diameter and lymph node metastases of invasive breast cancer diagnosed between 1969 and 1988 were analyzed and compared to cases diagnosed between 1929 and 1968. One hundred thirty patients have been treated without either axillary dissection or radiation therapy since 1980. RESULTS The mean and median diameters of invasive breast cancers decreased to 2.31 and 2.0 cm, respectively, between 1984 and 1988; 13% were less than 1 cm in diameter. Only 13% of patients had axillary metastases if the primary cancer was 1 cm or less in diameter in the last 10 years; 71% had only 1 or 2 nodes involved. Isolated local recurrence, total local recurrence, and distant metastases were unchanged when radiated and nonirradiated patients were compared. Axillary nodal recurrence was decreased in irradiated patients because the lower half of the axilla was treated. CONCLUSION In selected patients with very small invasive breast cancers detected by mammography, breast conservation without axillary dissection or radiation therapy may be used. Entirely outpatient treatment markedly reduces morbidity and cost, and furthers the gains from screening programs.

Soft Tissue Sarcoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.

Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for STS provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumors, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis, staging, and treatment of STS of the extremities, superficial trunk, or head and neck; outlines treatment recommendations by disease stage; and reviews the evidence to support the guidelines recommendations.

Surgical outcomes of patients with gastric carcinoma: the importance of primary tumor location and microvessel invasion

BACKGROUND This study was done to identify clinicopathologic predictors of disease-free survival (DFS) and overall survival (OS) among patients undergoing potentially curative resections for gastric carcinoma. METHODS We reviewed 110 patients surgically treated between 1987 and 2001. There were 74 men and 36 women with a mean age of 65.2 years (range 27 to 87 years). Log-rank tests and Kaplan-Meier survival curves were generated to determine clinicopathologic factors influencing DFS and OS. Significant factors were then determined with Cox multivariate analysis. RESULTS Median survival for all patients was 38.2 months and the estimated 5-year OS was 42.3%. There were no significant differences in DFS or OS for female sex, black race, or age>65. Symptoms associated with lower DFS were weight loss and palpable abdominal mass (P<.05), although none were predictive for OS. Median survival was markedly worse in patients undergoing esophagogastrectomy versus gastrectomy (26.8 vs 52.3 months; P<.05), although there were no significant differences between patients undergoing total gastrectomy versus subtotal gastrectomy. As expected, OS was inversely proportional to the American Joint Committee on Cancers tumor stage. When compared with patients with partial-thickness tumors (T(1-2)), full-thickness (T(3-4)) tumors had a decreased median survival (63.8 vs 27.9 months; P<.01). Although N(2) stage was associated with decreased survival (20.6 months), patient outcomes were similar for N(0) and N(1) stages (52.5 and 48.8 months). Lymphatic and capillary invasion (21.4 vs 45.3 months; P<.02) and proximal location of primary tumors (28.5 vs 58.6 months; P<.02) were the only other factors adversely affecting survival. Lauren classification and histologic grade were not significant predictors of patient outcomes. CONCLUSIONS In addition to the American Joint Committee on Cancer stage, microvessel involvement and tumor location are important predictors of DFS and OS in gastric cancer and should be included in risk stratification and selection criteria for patients entering novel adjuvant or neoadjuvant clinical trials.

National Assessment of Melanoma Care Using Formally Developed Quality Indicators

PURPOSE There is considerable variation in the quality of cancer care delivered in the United States. Assessing care by using quality indicators could help decrease this variability. The objectives of this study were to formally develop valid quality indicators for melanoma and to assess hospital-level adherence with these measures in the United States. METHODS Quality indicators were identified from available literature, consensus guidelines, and melanoma experts. Thirteen experts ranked potential measures for validity on the basis of the RAND/University of California, Los Angeles Appropriateness Methodology. Adherence with individual valid indicators and a composite measure of all indicators were assessed at 1,249 Commission on Cancer hospitals by using the National Cancer Data Base (NCDB; 2004 through 2005). RESULTS Of 55 proposed quality indicators, 26 measures (47%) were rated as valid. These indicators assessed structure (n = 1), process (n = 24), and outcome (n = 1). Of the 26 measures, 10 are readily assessable by using cancer registry data. Adherence with valid indicators ranged from 11.8% to 96.5% at the patient level and 3.7% to 83.0% at the hospital level. (Adherence required that >OR= 90% of patients at a hospital receive concordant care.) Most hospitals were adherent with 50% or fewer of the individual indicators (median composite score, five; interquartile range, four to seven). Adherence was higher for diagnosis and staging measures and was lower for treatment indicators. CONCLUSION There is considerable variation in the quality of melanoma care in the United States. By using these formally developed quality indicators, hospitals can assess their adherence with current melanoma care guidelines through feedback mechanisms from the NCDB and can better direct quality improvement efforts.

Effect of Hospital Type and Volume on Lymph Node Evaluation for Gastric and Pancreatic Cancer

HYPOTHESIS For gastric and pancreatic cancer, regional lymph node evaluation is important to accurately stage disease in a patient and may be associated with improved survival. We hypothesized that National Comprehensive Cancer Network (NCCN), National Cancer Institute (NCI)-designated institutions, and high-volume hospitals examine more lymph nodes for gastric and pancreatic malignant neoplasms than do low-volume centers and community hospitals. DESIGN Volume-outcome study. SETTING Academic research. PATIENTS Using the National Cancer Data Base (January 1, 2003, to December 31, 2004), patients were identified who underwent resection for gastric (n = 3088) and pancreatic (n = 1130 [pancreaticoduodenectomy only]) cancer. MAIN OUTCOME MEASURES Multivariable logistic regression analysis was used to assess the effect of hospital type and volume on nodal evaluation (>or=15 nodes). RESULTS Only 23.2% of patients with gastric cancer and 16.4% of patients with pancreatic cancer in the United States underwent evaluation of at least 15 lymph nodes. Patients undergoing surgery had more lymph nodes examined at NCCN-NCI hospitals than at community hospitals (median, 12 vs 6 for gastric cancer and 9 vs 6 for pancreatic cancer; P < .001). Patients at highest-volume hospitals had more lymph nodes examined than patients at low-volume hospitals (median, 10 vs 6 for gastric cancer and 8 vs 6 for pancreatic cancer; P < .001). On multivariable analysis, patients undergoing surgery at NCCN-NCI and high-volume hospitals were more likely to have at least 15 lymph nodes evaluated compared with patients undergoing surgery at community hospitals and low-volume centers (P < .001 and P =.02, respectively). CONCLUSIONS Nodal examination is important for staging, adjuvant therapy decision making, and clinical trial stratification. Moreover, differences in nodal evaluation may contribute to improved long-term outcomes at NCCN-NCI centers and high-volume hospitals for patients with gastric and pancreatic cancer.

Health Care System and Socioeconomic Factors Associated With Variance in Use of Sentinel Lymph Node Biopsy for Melanoma in the United States

PURPOSE Guidelines recommend sentinel lymph node biopsy (SLNB) for patients with clinical stage IB/II melanomas, but not clinical stage IA melanoma. This study examines factors associated with SLNB use for clinically node-negative melanoma. METHODS Patients diagnosed with clinically node-negative invasive melanoma in 2004 and 2005 were identified from the National Cancer Data Base. Regression models were developed to assess the association of clinicopathologic (sex, age, race/ethnicity, comorbidities, T stage), socioeconomic (insurance status, educational level, income), and hospital (hospital type, geographic area) factors with SLNB use. RESULTS A total of 16,598 patients were identified: 8,073 patients with clinical stage IA and 8,525 patients with clinical stage IB/II melanoma. For clinical stage IB/II melanoma, SLNB use was reported in 48.7% of patients. Patients with clinical stage IB/II melanoma were less likely to undergo SLNB if they were older than 75 years; had T1b tumors, no tumor ulceration, or head/neck or truncal lesions; were covered by Medicaid or Medicare; or lived in the Northeast, South, or West census regions. SLNB use was reported in 13.3% of patients with clinical stage IA melanoma and was more likely in patients who were younger than 56 years or lived in the Mountain or Pacific census regions. Patients treated at National Comprehensive Cancer Network-or National Cancer Institute-designated hospitals were most likely to undergo SLNB in adherence with national consensus guidelines. CONCLUSION SLNB use was associated with clinicopathologic factors but also with health system factors, including type of insurance, geographic area, and hospital type. These findings have implications for provider education and health policy.

Gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy.

BACKGROUND A gene expression profile (GEP) test able to accurately identify risk of metastasis for patients with cutaneous melanoma has been clinically validated. OBJECTIVE We aimed for assessment of the prognostic accuracy of GEP and sentinel lymph node biopsy (SLNB) tests, independently and in combination, in a multicenter cohort of 217 patients. METHODS Reverse transcription polymerase chain reaction (RT-PCR) was performed to assess the expression of 31 genes from primary melanoma tumors, and SLNB outcome was determined from clinical data. Prognostic accuracy of each test was determined using Kaplan-Meier and Cox regression analysis of disease-free, distant metastasis-free, and overall survivals. RESULTS GEP outcome was a more significant and better predictor of each end point in univariate and multivariate regression analysis, compared with SLNB (P < .0001 for all). In combination with SLNB, GEP improved prognostication. For patients with a GEP high-risk outcome and a negative SLNB result, Kaplan-Meier 5-year disease-free, distant metastasis-free, and overall survivals were 35%, 49%, and 54%, respectively. LIMITATIONS Within the SLNB-negative cohort of patients, overall risk of metastatic events was higher (∼30%) than commonly found in the general population of patients with melanoma. CONCLUSIONS In this study cohort, GEP was an objective tool that accurately predicted metastatic risk in SLNB-eligible patients.