Recurrence Patterns After Surgical Resection of Gastroenteropancreatic Neuroendocrine Tumors: Analysis From the National Comprehensive Cancer Network Oncology Outcomes Database.

OBJECTIVE: Current National Comprehensive Cancer Network guidelines for gastroenteropancreatic neuroendocrine tumors (GEPNETs) recommend complete (R0) surgical resection of the primary tumor and metastases, if feasible. However, large multicenter studies of recurrence patterns of GEPNETs after resection have not been performed. METHODS: Patients 18 years or older who presented to 7 participating National Comprehensive Cancer Network institutions between 2004 and 2008 with a new diagnosis of a small bowel, pancreas, or colon/rectum neuroendocrine tumor (NET) and underwent R0 resection of the primary tumor, and synchronous metastases, if present, were included in this analysis. Descriptive statistics and Kaplan-Meier estimates were used to calculate recurrence rates and time-associated end points, respectively. RESULTS: Of 294 patients with GEPNETs, 50% were male, 88% were White, and 99% had Eastern Cooperative Oncology Group performance status 0 to 1. The median age was 55 years (range, 20-90). The median follow-up time from R0 resection was 62.1 months. Recurrence rates were 18% in small bowel NETs (n = 110), 26% in pancreatic NETs (n = 141), and 10% in colon/rectum NETs (n = 50). The frequency of surveillance imaging was highly variable. CONCLUSIONS: R0 resection was associated with variable risk of recurrence across subtypes. Further research to inform refinement of guidelines for the appropriate duration of surveillance after R0 resection is needed.

Non-home Discharge and Prolonged Length of Stay After Cytoreductive Surgery and HIPEC.

BACKGROUND: Predictive models for nonhome discharge (NHD) have been proposed in major surgical specialties. The rates and risk factors associated with NHD and prolonged length of stay (PLOS) after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) have not been evaluated. The aim of this study is to identify risk factors for NHD and PLOS after CRS/HIPEC in a national cohort of patients. MATERIALS AND METHODS: CRS/HIPEC cases were identified from the National Surgical Quality Improvement Program 2011-2012 data set. Patients with an NHD or PLOS (>30 d) were compared with a group of patients discharged to home within 30 d. Univariate analysis was used to compare patient characteristics, operative variables, and postoperative complications among both groups. Multivariate regression analysis was used to identify independent predictors of NHD and PLOS. RESULTS: Five hundred fifty-six patients undergoing CRS/HIPEC were identified, of which 44 (7.9%) were not discharged to home within 30 d. The rate of NHD and PLOS in this cohort was 4.1% and 3.7%, respectively. Multivariate analysis identified age ≥65 y, pre-op albumin <3.0 g/dL, and having a multivisceral resection as independent predictors of NHD/PLOS. If all three predictors are met preoperatively, the probability of NHD/PLOS was calculated to be 30.2%. CONCLUSIONS: The main risk factors for NHD/PLOS after CRS/HIPEC were advanced age, hypoalbuminemia, and multivisceral resection. Adequate identification of these risk factors may facilitate preoperative discussion with patients, and improve discharge planning and resource utilization.

Failure to rescue following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) can significantly improve the survival in selected patients with peritoneal carcinomatosis. This study aims to identify perioperative patient characteristics predictive of failure to rescue (FTR), mortality following postoperative complications from CRS/HIPEC. METHODS: Patients suffering a complication following CRS/HIPEC between 2005 and 2013 were identified in the American College of Surgeons National Surgical Quality Improvement Program data set. FTR was defined as 30-d mortality in the setting of a complication. Patients who suffered FTR were compared against those who survived a complication (non-FTR). Predictors of FTR were identified using a multivariable logistic regression model. RESULTS: A total of 915 eligible CRS/HIPEC cases were identified. In all, 382 patients (42%) developed ≥1 postoperative complication, and 88 patients (10%) suffered ≥1 major complication. Seventeen patients died following a complication, amounting to an FTR rate of 4%. FTR patients were more likely than non-FTR patients to have dependent functional status (18% versus 2%, P = 0.01), have American Society of Anesthesiologists (ASA) class 4 status (29% versus 8%, P = 0.01), develop ≥3 complications (65% versus 24%, P < 0.01), and suffer a major complication (94% versus 20%, P < 0.01). The following were independently associated with FTR: ASA class 4 (odds ratio [OR]: 13.4, 95% confidence interval [CI], 1.2-146.8) and major complications (OR: 66.0, 95% CI, 8.4-516.6). CONCLUSIONS: ASA class 4, major morbidity, and likely dependent functional status are independent predictors of FTR following CRS/HIPEC to treat peritoneal carcinomatosis. Therefore, ASA class 4 and dependent functional status should be considered as contraindications for CRS/HIPEC and only offered in highly selective cases.

Phase 2 study of erlotinib combined with adjuvant chemoradiation and chemotherapy in patients with resectable pancreatic cancer.

PURPOSE: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. METHODS AND MATERIALS: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m(2) twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m(2) on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). RESULTS: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. CONCLUSION: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer.

Rectal cancer.

These NCCN Clinical Practice Guidelines in Oncology provide recommendations for the management of rectal cancer, beginning with the clinical presentation of the patient to the primary care physician or gastroenterologist through diagnosis, pathologic staging, neoadjuvant treatment, surgical management, adjuvant treatment, surveillance, management of recurrent and metastatic disease, and survivorship. This discussion focuses on localized disease. The NCCN Rectal Cancer Panel believes that a multidisciplinary approach, including representation from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology, is necessary for treating patients with rectal cancer.

National trends in the management and survival of surgically managed gallbladder adenocarcinoma over 15 years: a population-based analysis.

INTRODUCTION: National Comprehensive Cancer Network (NCCN) guidelines recommend hepatic resection and lymphadenectomy (LND) for gallbladder adenocarcinoma (GBA). We sought to evaluate compliance with these recommendations and to assess trends in the management and survival of patients with GBA. METHODS: Using Surveillance, Epidemiology and End Results (SEER)-Medicare-linked data, we identified 2,955 patients with GBA who underwent cancer-directed surgery from 1991 to 2005. We assessed clinicopathologic data, trends in surgical management, and survival. RESULTS: From 1991 to 2005, preoperative evaluation included CT (62%), MRI (6%), and PET (2%). Only 383 (13%) patients underwent radical resection/hepatectomy with a temporal increase over the study period (1991-1995, 12%; 1996-1999, 10%; 2000-2002, 12.0%; 2003-2005, 16%; P < 0.001). For patients undergoing radical resection/hepatectomy, LND ≥ 3 nodes was performed in 96 (3%) patients. Among patients who had LND, 47% had nodal metastasis. The overall 1-, 3-, and 5-year survival was 56%, 30%, and 21%. On multivariate analysis, radical resection/hepatectomy (hazard ratio (HR) = 0.71) and LND ≥ 3 nodes (HR = 0.56) were independently associated with increased survival. There was no significant improvement in survival over time (P = 0.60). CONCLUSIONS: Compliance with NCCN guidelines for GBA remains poor. Survival of patients with surgically managed GBA has not improved over time.

Adjuvant chemoradiation therapy for adenocarcinoma of the distal pancreas.

BACKGROUND: This study was designed to examine the effect of adjuvant 5-FU-based chemoradiation therapy (CRT) after distal pancreatectomy for adenocarcinoma of the distal pancreas. METHODS: All patients underwent curative resection for adenocarcinoma of the distal pancreas between December 1985 and June 2006. Patients who received adjuvant CRT were compared with those who underwent surgery alone. A Kaplan-Meier estimate of the survival curve was used to determine estimates of the median survival and proportion alive at 1 and 2 years; log-rank tests were used to make comparisons between groups. RESULTS: A total of 123 patients underwent distal pancreatectomy; 29 patients were excluded for distant metastases at the time of surgery (n = 12, 10%) or before adjuvant therapy (n = 11, 9%), death within 2 months of surgery (n = 2, 2%), or if CRT treatment status was unknown (n = 4, 3%). Of the remaining 94 patients, 72% received adjuvant 5-FU-based CRT and 28% underwent surgery alone. Overall median survival was 16.2 (95% confidence interval (CI), 13.1-18.9) months. The groups were similar with respect to tumor size, nodal status, and margin status. There was no significant difference in overall survival between patients treated with adjuvant CRT versus surgery alone (p = 0.23). An exploratory subgroup analysis suggested a potential survival benefit of adjuvant CRT in patients with lymph node metastases (16.7 vs. 12.1 months, p < 0.01). CONCLUSIONS: Adjuvant CRT did not increase survival compared with surgery alone; however, patients with node-positive disease appear to benefit from adjuvant CRT.

Effect of age on survival benefit of adjuvant chemotherapy in elderly patients with Stage III colon cancer.

OBJECTIVES: To estimate the modifying effect of age on the survival benefit associated with adjuvant chemotherapy receipt in elderly patients with a diagnosis of Stage III colon cancer. DESIGN: Observational, retrospective cohort study using two samples: an overall sample of 7,182 patients to provide externally valid analyses and a propensity score-matched sample of 3,016 patients to provide more internally valid analyses by reducing the presence of treatment endogeneity. An interval-censored survival model with a complementary log-log link was used. Hazard ratios and 95% confidence intervals were obtained for all regressions. SETTINGS: Data from the National Cancer Institute's Surveillance, Epidemiology and End Results database and the linked Medicare enrollment and claims database were used. PARTICIPANTS: Selected patients were aged 66 and older and had a diagnosis of Stage III colon cancer. Patients were followed from surgery to time of death or censorship. MEASUREMENTS: The outcome was colon cancer-specific death during the follow-up period. Receipt of adjuvant chemotherapy was measured according to the presence of a claim for 5-fluorouracil or leucovorin within 6 months after surgery. RESULTS: All elderly patients had a significant survival benefit associated with adjuvant chemotherapy receipt, although the survival benefit of adjuvant chemotherapy was not uniform across all age groups. CONCLUSION: These findings have important clinical and policy implications for the risk-benefit calculation induced by treatment in older patients with Stage III colon cancer. The results suggest that there is a benefit from chemotherapy, but the benefit is lower with older age.

Determining pattern of recurrence following pancreaticoduodenectomy and adjuvant 5-flurouracil-based chemoradiation therapy: effect of number of metastatic lymph nodes and lymph node ratio.

BACKGROUND: There are limited data on patterns of recurrence and factors associated with local recurrence following pancreaticoduodenectomy for pancreatic adenocarcinoma and adjuvant 5-flurouracil-based chemoradiation therapy. METHODS AND MATERIALS: Between 1995 and 2005, 905 patients underwent pancreaticoduodenectomy for pancreatic adenocarcinoma; 154 patients had complete pattern of recurrence data available. RESULTS: At median follow-up of 20.2 months, 103 (66.9%) patients recurred with median time to recurrence of 16.2 months. Most patients recurred with distant disease only (68.9%), while 21.4% patients recurred with local disease only; ten (9.7%) patients recurred with local and distant disease. Several factors were associated with local recurrence: poor tumor differentiation (hazards ration [HR] 2.39) and presence of metastatic lymph nodes (HR 1.89, both p < 0.05). Among N1 patients, poor tumor differentiation (HR 3.92), >5 metastatic LN (HR 3.75), and lymph node ratio (LNR) >0.4 (HR 2.96) had the highest risk of local recurrence (all p < 0.05). Increasing LNR was associated with an incremental increased risk of local recurrence (LNR <0.2, 21.3% versus LNR >or=0.2 to 0.4, 25.2% versus LNR >0.4, 40.4%; p < 0.05). CONCLUSIONS: Although most patients who receive standard 5-flurouracil-based chemoradiation therapy will ultimately succumb to distant disease, about 30% recur locally. Poor tumor differentiation, a high number of metastatic LN (>5), and LNR >0.4 are associated with the highest risk of local failure. In these patients, radiation dose escalation and/or a combination of radiation with novel chemotherapeutic agents may be necessary to improve outcomes.

Transcatheter arterial chemoembolization of liver tumors: effects of embolization protocol on injectable volume of chemotherapy and subsequent arterial patency.

The purpose of this study was to determine whether transcatheter arterial chemoembolization (TACE) protocol affects the total volume of chemotherapy injected into the liver as well as subsequent arterial patency. A total of 160 patients with primary or secondary liver cancer were treated with 3 different chemoembolization protocols at a single institution. Data were analyzed retrospectively. Group 1 (n = 36) consisted of slurry of chemotherapy, oil and polyvinyl alcohol particles (PVA), group 2 (n = 91), chemotherapy and oil followed by PVA, and group 3 (n = 33), chemotherapy and oil followed by Gelfoam pledgets. The total volume of chemotherapy injected into the liver was recorded. Arterial patency was determined during subsequent chemoembolizations. The mean percentage of total intended chemotherapy dose administered was 54.6% for group 1, 75.3% for group 2, and 80.6% for group 3. Arterial patency at follow-up angiography was 56% for group 1, 74% for group 2, and 81% for group 3. The slurry protocol (group 1) significantly reduced arterial patency and injectable volume of chemotherapy during TACE.