Edith Brutcher

Modified FOLFIRINOX regimen with improved safety and maintained efficacy in pancreatic adenocarcinoma.

Objectives FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, and irinotecan) as compared with gemcitabine in pancreatic cancer (PC) has superior activity and increased toxicity. The bolus 5-FU contributes to the toxicity. We hypothesized that the elimination of bolus 5-FU and use of hematopoietic growth factor will improve the safety profile without compromising the activity of FOLFIRINOX. Methods Sixty patients with PC treated with modified FOLFIRINOX (no bolus 5-FU) were reviewed. Patients were divided into metastatic or nonmetastatic (locally advanced or borderline resectable) disease. Toxicity, response rate, progression-free survival, and overall survival were evaluated. Results Nonmetastatic and metastatic disease were present in 24 (40%) and 36 (60%) patients, respectively. The incidence of grade 4 neutropenia, grade 3/4 diarrhea, and fatigue were 3%, 13%, and 13%, respectively. Response rate was 30%. The median progression-free survival for nonmetastatic disease was 13.7 months (95% confidence interval [CI], 9.6–24.6 months), and that for metastatic disease was 8.5 months (95% CI, 3.7–11.0 months), respectively. The median overall survival for nonmetastatic disease was 17.8 months (95% CI, 9.9 months to not estimable), and that for metastatic disease was and 9.0 months (95% CI, 7.1 months to not estimable), respectively. Conclusions Modified FOLFIRINOX has an improved safety profile with maintained efficacy in metastatic PC. Modified FOLFIRINOX has promising activity in nonmetastatic disease.

Incidence and Survival of Appendiceal Mucinous Neoplasms: A SEER Analysis.

Objectives: The aim of this study is to characterize the changes in the incidence, presentation, surgical treatment, and survival of patients with appendiceal mucinous neoplasm (AMN) over the past 4 decades using nationwide cancer surveillance data. Methods: Patients with the diagnosis of AMN were identified in the Surveillance Epidemiology and End Results (SEER) database. Information on demographics, disease characteristics, and surgical treatment was collected. Temporal changes in AMN incidence, characteristics of cases, and survival were analyzed from 1973 to 2011. Determinants of overall survival (OS) were examined using both crude and multivariable Cox proportional hazard models. Results: The overall incidence rate of AMN increased on average 3.1%/1,000,000 persons-years (P<0.001). A significant decline in the age at diagnosis was observed (P=0.014). The proportion of patients presenting with distant disease at diagnosis also significantly increased (P=0.004). Five-year survival of patients with distant stage AMN increased at a rate of 3.5%/y between 1984 and 2006 (P<0.001). Median OS was not reached for localized and regional stage disease. Median OS for distant stage disease was 42 months. Conclusions: There has been an increase in the overall incidence of AMN with an observed increase in the proportion of younger age and distant stage at diagnosis. The OS has improved over time.

Clinicopathologic Features and Outcome of Young Adults With Stage IV Colorectal Cancer.

Purpose:Colorectal cancer has a distinct clinicopathologic presentation in younger patients. The aim of this paper was to evaluate the outcome of younger (age below 50 y) and older patients with stage IV (advanced) colorectal cancer in the modern era of combination chemotherapy. Methods:Cases of metastatic colorectal cancer reported in Surveillance, Epidemiology, and End Results registry (1973 to 2008) were reviewed. Demographics, tumor characteristics, and overall and cancer-specific survivals in patients below 50 and above 50 years of age were compared by Cox proportional hazard analyses. Joinpoint regression analysis was used to evaluate secular trends in 2-year survival. Results:Younger patients had a greater proportion of negative clinicopathologic features (male sex, African American ethnicity, and signet ring or mucinous histology). In multivariate analysis, older age, male sex, African American ethnicity, right-sided tumors, and signet ring histology were associated with higher mortality risk. Younger patients had improved survival (hazard ratio 0.72; 95% confidence interval: 0.70-0.75) compared with older patients, whereas all patients experienced increased 2-year survival by joinpoint analysis beginning in 1999-2000. Conclusions:The results confirm decreased mortality from advanced colorectal cancer in the era of modern combination chemotherapy in younger and older patients. Younger age, non–right-sided tumors, and absence of signet ring histology significantly associate with better survival.

Appendiceal Neuroendocrine, Goblet and Signet-Ring Cell Tumors: A Spectrum of Diseases with Different Patterns of Presentation and Outcome

Purpose Appendiceal tumors are a heterogeneous group of diseases that include typical neuroendocrine tumors (TNET), goblet cell carcinoids (GCC), and atypical GCC. Atypical GCC are classified into signet-ring cell cancers (SRCC) and poorly differentiated appendiceal adenocarcinoids. The prognosis and management of these diseases is unclear because there are no prospective studies. The aim of this study is to assess the characteristics and outcome of appendiceal TNET, GCC, and SRCC patients. Materials and Methods Appendiceal TNET, GCC, and SRCC patients diagnosed between 1973 and 2011 were identified in the Surveillance Epidemiology and End Results (SEER) database. Demographics, type of surgery, and clinicopathologic characteristics were collected. Survival functions were estimated by the Kaplan-Meier method, and log-rank test was used to assess the difference in overall survival (OS) among the three histologies. Results The SEER database yielded 1,021 TNET patients, 1,582 with GCC, and 534 SRCC patients. TNET presented at a younger age (p < 0.001). Patients with SRCC presented with advanced stage disease (p < 0.001). The median OS (mOS) for GCC and TNET patients was not reached; mOS for SRCC was 24 months. Multivariate analysis stratified for stage revealed significantly longer survival for TNET and GCC than SRCC (p < 0.001). Conclusion This is the largest report to date for appendiceal neuroendocrine tumor patients, suggesting a spectrum of diseases with different characteristics and outcomes. In this report, we present a treatment approach for this complex spectrum of disease, based on the experience of Ohio State and Emory Universities investigators.

Treatment utilization and surgical outcome of ampullary and duodenal adenocarcinoma

Ampullary (AMP‐A) and duodenal adenocarcinomas (DA) are rare tumors. The literature regarding treatment and outcome is very limited. The objective of this project is to compare the outcomes of AMP‐A and DA.

Hyperthermic Intraperitoneal Chemotherapy Following Cytoreductive Surgery Improves Outcome in Patients With Primary Appendiceal Mucinous Adenocarcinoma: A Pooled Analysis From Three Tertiary Care Centers

PURPOSE Appendiceal mucinous neoplasms (AMN) are a rare heterogeneous group of diseases. In the absence of randomized trials, AMN management is controversial. The goal of this study was to evaluate the impact of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery on survival in AMN patients. PATIENTS AND METHODS Patient data including demographics, pathology, type of therapy, and outcomes were collected from Emory University, the Ohio State University, and Wayne State University databases. One of the three centers did not use HIPEC. Statistical analysis evaluating overall survival (OS) of AMN patients was performed. RESULTS Between 1990 and 2010, 163 AMN patients were identified. Histology showed 60 patients had diffuse peritoneal adenomucinosis, 88 had peritoneal mucinous carcinomatosis (PMCA), and 15 had PMCA with indeterminate or discordant features. Complete surgical resection was achieved in 76 patients. HIPEC was used in 79 patients. The median OS was 77 months for patients who received HIPEC compared with 25 months for patients who did not (p < .001). In multivariable analysis, histopathologic subtype (p < .001), complete surgical resection (p < .001), and HIPEC (p < .001) were independent predictors for improved OS. A survival advantage for AMN patients treated at HIPEC-treating centers was observed (p = .0026). After adjusting for HIPEC therapy, no significant survival difference was observed between the non-HIPEC-treating center and the HIPEC-treating centers (p = .094). CONCLUSION The addition of HIPEC to cytoreductive surgery likely provides a survival advantage and should be considered in the treatment strategy for AMN.

Combination gemcitabine/cisplatin therapy and ERCC1 expression for resected pancreatic adenocarcinoma: Results of a Phase II prospective trial

Standard adjuvant treatment for pancreatic adenocarcinoma (PDAC) is gemcitabine [Gem(CONKO‐001: Gem vs. placebo DFS:13.4 vs. 6.7 mo; P < 0.001; OS:22.8 vs. 20.2 mo; P = 0.01)]. Addition of cisplatin (Cis) to Gem has resulted in increased PFS for advanced and metastatic disease, which may be predicted by low expression of excision repair cross‐complementing group–1 (ERCC1), the key enzyme in nucleotide excision repair. This Phase II prospective trial assesses outcomes of patients treated with adjuvant Gem/Cis, stratifying results by tumor ERCC1 expression.

Phase 1b study of pasireotide, everolimus, and selective internal radioembolization therapy for unresectable neuroendocrine tumors with hepatic metastases: Pasireotide, Everolimus, and SIRT in NETs

Neuroendocrine tumors (NETs) metastasize to the liver. Everolimus and selective internal radioembolization (SIRT) are approved treatments. Pasireotide is a somatostatin analogue with an affinity for somatostatin receptors 1, 2, 3, and 5. Everolimus and pasireotide may potentiate SIRT radiosensitization and inhibit rebound angiogenesis. This study evaluated the safety of pasireotide, everolimus, and SIRT.