Preoperative Treatment of Locally Advanced Rectal Cancer.

BACKGROUND: Pelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain. METHODS: We conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy. Adults with rectal cancer that had been clinically staged as T2 node-positive, T3 node-negative, or T3 node-positive who were candidates for sphincter-sparing surgery were eligible to participate. The primary end point was disease-free survival. Noninferiority would be claimed if the upper limit of the two-sided 90.2% confidence interval of the hazard ratio for disease recurrence or death did not exceed 1.29. Secondary end points included overall survival, local recurrence (in a time-to-event analysis), complete pathological resection, complete response, and toxic effects. RESULTS: From June 2012 through December 2018, a total of 1194 patients underwent randomization and 1128 started treatment; among those who started treatment, 585 were in the FOLFOX group and 543 in the chemoradiotherapy group. At a median follow-up of 58 months, FOLFOX was noninferior to chemoradiotherapy for disease-free survival (hazard ratio for disease recurrence or death, 0.92; 90.2% confidence interval [CI], 0.74 to 1.14; P = 0.005 for noninferiority). Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy group. The groups were similar with respect to overall survival (hazard ratio for death, 1.04; 95% CI, 0.74 to 1.44) and local recurrence (hazard ratio, 1.18; 95% CI, 0.44 to 3.16). In the FOLFOX group, 53 patients (9.1%) received preoperative chemoradiotherapy and 8 (1.4%) received postoperative chemoradiotherapy. CONCLUSIONS: In patients with locally advanced rectal cancer who were eligible for sphincter-sparing surgery, preoperative FOLFOX was noninferior to preoperative chemoradiotherapy with respect to disease-free survival. (Funded by the National Cancer Institute; PROSPECT ClinicalTrials.gov number, NCT01515787.).

Optimal care and survival for signet-ring cell and non-signet-ring cell gastric cancer are more achievable at academic cancer centers.

BACKGROUND: Western literature lacks large-scale population studies comparing the influence of academic and high-volume (HV) versus low-volume (LV) cancer centers on gastric cancer oncologic outcomes. METHODS: The National Cancer Database from 2004 to 2016 was used. RESULTS: 22871 patients were studied. Patients with stage III signet-ring cell gastric carcinoma (SRGC) received neoadjuvant treatment (NAT) more frequently at academic and HV comprehensive cancer centers (OR: 4.27 and 2.42; p < 0.0001 and 0.009) compared to community centers. Patients with stage III non-SRGC (NSRGC) had a 2.4 times higher odds of receiving NAT at academic centers. The R1 resection rate for NSRGC was lower at academic centers (OR: 0.67; p = 0.0018). Lymph node harvest ≥15 nodes was 1.6 and 1.9 times higher at academic centers for NSRGC and SRGC, respectively. Patients treated at academic centers had a significantly improved overall survival (OS). CONCLUSIONS: Treatment at academic centers is associated with significant improvements in oncologic metrics and OS.

Granular cell tumor experience at a comprehensive cancer center.

BACKGROUND: Granular cell tumors (GCTs) are rare lesions occurring almost anywhere in the body. Multiple case reports have been published. However, there are very few large-scale studies regarding GCT. The aim of this study was to define characteristics, treatment patterns and outcomes of patients with GCT. METHODS: An institutional review board-approved retrospective chart review was performed. Descriptive statistics, chi-square analyses, and Kaplan-Meier survival estimates were produced. RESULTS: Fifty patients were treated for GCT at our institution between 1992 and 2015. The median age was 47 y; 62% of patients were female and 64% were whites. Median tumor size was 0.8 cm. Four percent of patients had malignant tumors, 10.0% had atypical tumors, and 86.0% had benign tumors. The most frequent location of tumors was the gastrointestinal tract (n = 30; 60%), followed by skin/subcutaneous tissues (n = 19; 38%), then respiratory tract (n = 1; 2%). Most patients underwent surgical excision or endoscopic removal of their tumors without prior biopsy. Three patients (6%) had multifocal tumors; they were more likely to experience recurrence than patients with unifocal tumors (33.3% versus 10.6%, respectively; P = 0.05). Six patients (12.0%) experienced recurrence, with a median time to recurrence of 13.5 mo. Overall cancer-specific 5-y survival was 98.0%. Overall recurrence-free 5-y survival was 86.4%. Patients with atypical tumors had a lower recurrence-free 5-y survival rate than those with benign tumors (75.0% versus 89.7%, respectively; P = 0.04). CONCLUSIONS: Patients with GCT fair well, particularly when tumors are benign. Patients with multifocal tumors are more likely to experience recurrence and should be closely monitored.

Incidence of minimally invasive colorectal cancer surgery at National Comprehensive Cancer Network centers.

BACKGROUND: Laparoscopic colectomy has been shown to have equivalent oncologic outcomes to open colectomy for the management of colon cancer, but its adoption nationally has been slow. This study investigates the prevalence and factors associated with laparoscopic colorectal resection at National Comprehensive Cancer Network (NCCN) centers. METHODS: Data on patients undergoing surgery for colon and rectal cancer at NCCN centers from 2005 to 2010 were obtained from chart review of medical records for the NCCN Outcomes Project and included information on socioeconomic status, insurance coverage, comorbidity, and physician-reported Eastern Cooperative Oncology Group (ECOG) performance status. Associations between receipt of minimally invasive surgery and patient and clinical variables were analyzed with univariate and multivariable logistic regression. All statistical tests were two-sided. RESULTS: A total of 4032 patients, diagnosed between September 2005 and December 2010, underwent elective colon or rectal resection for cancer at NCCN centers. Median age of colon cancer patients was 62.6 years, and 49% were men. The percent of colon cancer patients treated with minimally invasive surgery (MIS) increased from 35% in 2006 to 51% in 2010 across all centers but varied statistically significantly between centers. On multivariable analysis, factors associated with minimally invasive surgery for colon cancer patients who had surgery at an NCCN institution were older age (P = .02), male sex (P = .006), fewer comorbidities (P ≤ .001), lower final T-stage (P < .001), median household income greater than or equal to $80000 (P < .001), ECOG performance status = 0 (P = .02), and NCCN institution (P ≤ .001). CONCLUSIONS: The use of MIS increased at NCCN centers. However, there was statistically significant variation in adoption of MIS technique among centers.

Predicting pathological response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer using 18FDG-PET/CT.

BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemoradiation (CRT) has been observed in 15-30% of patients with locally advanced rectal cancer (LARC). The objective of this study was to determine whether PET/CT can predict pCR and disease-free survival in patients receiving CRT with LARC. METHODS: This is a retrospective review of patients with EUS-staged T3-T4, N+rectal tumors treated with CRT, who underwent pre/post-treatment PET/CT from 2002-2009. All patients were treated with CRT and surgical resection. Standardized uptake value (SUV) of each tumor was recorded. Logistic regression was used to analyze the association of pre-CRT SUV, post-CRT SUV, %SUV change, and time between CRT and surgery, compared with pCR. Kaplan-Meier estimation evaluated significant predictors of survival. RESULTS: Seventy patients (age 62 years; 42M:28F) with preoperative stage T3 (n=61) and T4 (n=9) underwent pre- and post-CRT PET/CT followed by surgery. The pCR rate was 26%. Median pre-CRT SUV was 10.8, whereas the median post-CRT SUV was 4 (P=0.001). Patients with pCR had a lower median post-CRT SUV compared with those without (2.7 vs. 4.5, P=0.01). Median SUV decrease was 63% (7.5-95.5%) and predicted pCR (P=0.002). Patients with a pCR had a greater time interval between CRT and surgery (median, 58 vs. 50 days) than those without (P=0.02). Patients with post-CRT SUV<4 had a lower recurrence compared with those without (P=0.03). Patients with SUV decrease≥63% had improved overall survival at median follow-up of 40 months than those without (P=0.006). CONCLUSIONS: PET/CT can predict response to CRT in patients with LARC. Posttreatment SUV, %SUV decrease, and greater time from CRT to surgery correlate with pCR. Post-CRT, SUV<4, and SUV decrease≥63% were predictive of recurrence-free and overall survival.

Limited survival in patients with carcinomatosis from foregut malignancies after cytoreduction and continuous hyperthermic peritoneal perfusion.

Peritoneal carcinomatosis is a frequent mode of metastasis in patients with gastric, duodenal, or pancreatic cancer. Survival in this setting is short and therapeutic options are limited. This analysis examines the outcomes of 18 patients treated with operative cytoreduction and continuous hyperthermic peritoneal perfusion. Eighteen patients (6 males and 12 females) with gastric (n = 9), pancreatic (n = 7), or duodenal (n = 2) cancer were treated on protocol. Patients underwent optimal cytoreduction (complete gross resection, 11; minimal residual disease, 7) and a 90-minute perfusion with cisplatin. Clinical parameters and tumor and treatment characteristics were analyzed. Survival curves were estimated using the Kaplan-Meier method. Procedures included gastrectomy (n = 8), pancreaticoduodenectomy (n = 3), and hemicolectomy (n = 2). After cytoreduction, patients had no evidence of residual disease (n = 11), fewer than 100 implants less than 5 mm (n = 1), more than 100 implants between 5-10 mm (n = 3), or multiple implants with greater than 1 cm (n = 3). Five patients received a postoperative intraperitoneal dwell with 5-fluorouracil and paclitaxel. There was one perioperative mortality, and complications occurred in 10 patients. The median progression-free survival was 8 months (mean, 10 months; range, 1-47 months) with a median overall survival of 8 months (mean, 18 months; range, 1-74 months). In this cohort, peritoneal perfusion with cisplatin used to treat foregut malignancies has a high incidence of complications and does not significantly alter the natural history of the disease. Investigation of novel therapeutic approaches should be considered.