Clinical Stage of Cancer Affects Perioperative Mortality for Gastrointestinal Cancer Surgeries.

BACKGROUND: The impact of the stage of cancer on perioperative mortality remains obscure. The purpose of this study was to investigate whether cancer stage influences 30-d mortality for gastric, pancreatic, and colorectal cancers. METHODS: Data were collected from the National Cancer Database for patients undergoing resections for cancers of the stomach, pancreas, colon, or rectum between 2004 and 2015. The main analysis was conducted among patients with cancer stages 1-3. A sensitivity analysis also included cancer stage 4. Descriptive statistics were used to compare the patients' baseline characteristics. Generalized linear mixed models were used to evaluate the relationship between stage and 30-d mortality, controlling for other disease-, patient- and hospital-level factors. Pseudo R2 statistics (%Δ pseudo R2) were used to quantify the relative explanatory capacity of the variables to the model for 30-d mortality. All analyses were performed using SAS 9.4. RESULTS: The cohort included 24,468, 28,078, 176,285, and 64,947 patients with stomach, pancreas, colon, and rectal cancers, respectively. After adjusting for other variables, 30-d mortality was different by stage for all cancer types examined. The factor most strongly associated with 30-d mortality was age (%Δ pseudo R2 range 14%-39%). The prognostic impact of cancer stage (Stages 1, 2, or 3) on 30-d mortality was comparable to that of the Charlson comorbidity index. CONCLUSIONS: Cancer stage contributes to explaining differences observed in short-term mortality for gastrointestinal cancers. Short-term mortality models would benefit by including more granular cancer stage, beyond disseminated status alone.

Modest advances in survival for patients with colorectal-associated peritoneal carcinomatosis in the era of modern chemotherapy.

BACKGROUND: The treatment of metastatic colorectal cancer (CRC) has evolved rapidly over the last decade, with combination chemotherapy and targeted biologic agents leading to significant improvements in survival. Despite these advances, little is known about their effectiveness in CRC-associated peritoneal carcinomatosis. The purpose of this study was to evaluate outcomes in patients with CRC-associated PC treated in the era of modern chemotherapy. METHODS: We retrospectively reviewed an institutional tumor database from 1996 to 2008. Survival data were evaluated for patients treated with PC before and after 2003. No patients before 2003 were treated with combination chemotherapy or biologic therapy. The modern chemotherapy group consisted of patients treated after 2003. Survival curves were estimated. RESULTS: Overall, 173 patients were identified. Median follow-up was 8.6 months. Median survival in the historic group (n = 91) was 8.9 months and 16.3 months in the modern chemotherapy group (n = 82) (P < 0.004). Age was the only significant covariate. The survival difference between the modern chemotherapy cohort and control cohort persisted after adjustment for age. In a subset of patients in the modern chemotherapy era group, for which treatment regimen could be definitively identified, survival was even greater-23.8 months. CONCLUSIONS: Patients with CRC-associated PC treated with modern combination chemotherapy and biologic therapy have a significantly longer median survival compared to our historical cohort. Despite these improvements, outcomes still remain poor. Therapeutic adjuncts such as surgical cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) in appropriately selected patients remain promising options to improve outcomes for patients with peritoneal-based disease.

Does preoperative therapy optimize outcomes in patients with resectable pancreatic cancer?

The objective of this study was to compare survival between all patients with radiographically resectable adenocarcinoma of the proximal pancreas who underwent preoperative chemoradiation therapy (PRE-OP CRT) or surgical exploration first (SURGERY) with "intention to resect." Pancreatic cancer patients who undergo resection after PREOP CRT live longer than patients who undergo resection without PREOP CRT, a difference that may be attributable to patient selection. We retrospectively identified 236 patients with pancreatic head adenocarcinoma seen between 1999 and 2007 with sufficient data to be confirmed medically and radiographically resectable. The outcomes of 144 patients who underwent PREOP CRT were compared to those of 92 patients who proceeded straight to SURGERY. The groups were similar in age and gender. Tumors were slightly larger in the PREOP CRT group (mean 2.5 cm vs. 2.1 cm, P < 0.01), and there were trends toward more venous abutment (54% vs. 39%, P = 0.06) and a higher Charlson comorbidity index (P = 0.1). In the PREOP CRT group, 76 patients (53%) underwent resection, 28 (19%) had metastatic and 17 (12%) locally unresectable disease after PREOP CRT, and 23 (16%) were not explored due to performance status or loss to follow-up. In the SURGERY group, 68 patients (74%) underwent resection. Sixteen patients (17%) had metastatic and eight patients (9%) locally unresectable disease at exploration. In patients who underwent resection, the PREOP CRT group had smaller pathologic tumor size and lower incidence of positive lymph nodes than the SURGERY group but no difference in positive margins or need for vascular resection. Median overall survival (OS) in patients undergoing resection was 27 months in the PREOP CRT group and 17 months in the SURGERY group (P = 0.04). Median OS in all patients treated with PREOP CRT or surgically explored with intention to resect was 15 and 13 months, respectively, with superimposable survival curves. Despite a lower resection rate, the PREOP CRT group as a whole had a similar OS to the SURGERY group as a whole. For patients who underwent resection, those in the PREOP CRT had longer survival than those in the SURGERY group, suggesting that PREOP CRT allows better patient selection for resection. PREOP CRT should be considered an acceptable alternative for most patients with resectable pancreatic cancer.

Understanding Racial Disparities in Gastrointestinal Cancer Outcomes: Lack of Surgery Contributes to Lower Survival in African American Patients.

BACKGROUND: Race/ethnicity-related differences in rates of cancer surgery and cancer mortality have been observed for gastrointestinal (GI) cancers. This study aims to estimate the extent to which differences in receipt of surgery explain racial/ethnic disparities in cancer survival. METHODS: The National Cancer Database was used to obtain data for patients diagnosed with stage I-III mid-esophageal, distal esophagus/gastric cardia (DEGC), noncardia gastric, pancreatic, and colorectal cancer in years 2004-2015. Mediation analysis was used to identify variables influencing the relationship between race/ethnicity and mortality, including surgery. RESULTS: A total of 600,063 patients were included in the study: 3.5% mid-esophageal, 12.4% DEGC, 4.9% noncardia gastric, 17.0% pancreatic, 40.1% colon, and 22.0% rectal cancers. The operative rates for Black patients were low relative to White patients, with absolute differences of 21.0%, 19.9%, 2.3%, 8.3%, 1.6%, and 7.7%. Adjustment for age, stage, and comorbidities revealed even lower odds of receiving surgery for Black patients compared with White patients. The observed HRs for Black patients compared with White patients ranged from 1.01 to 1.42. Mediation analysis showed that receipt of surgery and socioeconomic factors had greatest influence on the survival disparity. CONCLUSIONS: The results of this study indicate that Black patients appear to be undertreated compared with White patients for GI cancers. The disproportionately low operative rates contribute to the known survival disparity between Black and White patients. IMPACT: Interventions to reduce barriers to surgery for Black patients should be promoted to reduce disparities in GI cancer outcomes.See related commentary by Hébert, p. 438.

Resected pancreatic neuroendocrine tumors: patterns of failure and disease-related outcomes with or without radiotherapy.

PURPOSE: Pancreatic neuroendocrine tumors (NET) are rare and have better disease-related outcomes compared with pancreatic adenocarcinoma. Surgical resection remains the standard of care, although many patients present with locally advanced or metastatic disease. Little is known regarding the use of radiotherapy in the prevention of local recurrence after resection. To better define the role of radiotherapy, we performed an analysis of resected patients at our institution. METHODS: Between 1994 and 2009, 33 patients with NET of the pancreatic head and neck underwent treatment with curative intent at Duke University Medical Center. Sixteen patients were treated with surgical resection alone while an additional 17 underwent resection with adjuvant or neoadjuvant radiation therapy, usually with concurrent fluoropyrimidine-based chemotherapy (CMT). Median radiation dose was 50.4 Gy and median follow-up 28 months. RESULTS: Thirteen patients (39%) experienced treatment failure. Eleven of the initial failures were distant, one was local only and one was local and distant. Two-year overall survival was 77% for all patients. Two-year local control for all patients was 87%: 85% for the CMT group and 90% for the surgery alone group (p = 0.38). Two-year distant metastasis-free survival was 56% for all patients: 46% and 69% for the CMT and surgery patients, respectively (p = 0.10). CONCLUSIONS: The primary mode of failure is distant which often results in mortality, with local failure occurring much less commonly. The role of radiotherapy in the adjuvant management of NET remains unclear.