Prognostic Impact of Tumor Status, Nodal Status and Tumor Sidedness in Metastatic Colon Cancer.

Background Locally advanced primary tumors have been associated with poor overall survival (OS) in non-metastatic colon cancer. However, their impact on metastatic colon cancer (mCC) is not fully defined. The association between primary tumor location and prognosis in mCC is also evolving. Methods Using National Cancer Data Base, we identified a cohort of 25,377 patients diagnosed with mCC from 2004-2009. Chi-square test was used for descriptive analyses, while all potential prognostic factors were evaluated using Kaplan-Meier survival estimates and Cox proportional hazards regression modeling. Results The five-year OS for the entire study cohort was 12.3%. Factors associated with significant survival impact in multivariate analysis included age, gender, race, comorbidity index, academic level of treating institution, insurance status, income, year of diagnosis, primary tumor site, histologic differentiation, pathologic tumor stage (pT), pathologic nodal stage (pN), and modality of chemotherapy. pT1 lesions demonstrated poor prognosis in stage IV colon cancers, not statistically different when compared to survival outcomes observed in cases with pT4 lesions. Regional nodal involvement demonstrated poor OS in full cohort analysis and subgroup analysis independent of primary tumor location. Both right-sided and transverse colon tumors had similarly worse OS compared to left-sided tumors (right-sided: HR: 1.21, 95% CI: 1.17-1.25; transverse: HR: 1.21, 95% CI: 1.15-1.27). Conclusions T1 lesions arising from right-side or transverse colon portend a poor prognosis in mCC, while regional lymph node involvement by itself is an independent poor prognostic factor. Right-sided tumors are associated with poor outcomes than left-sided tumors, suggesting the role of underlying molecular or biologic variants.

Adjuvant Chemotherapy and Tumor Sidedness in Stage II Colon Cancer: Analysis of the National Cancer Data Base.

Background: Current guidelines recommend discussion of adjuvant chemotherapy (AC) for stage II colon cancer (CC) with high-risk features despite lacking conclusive randomized trial data. We examined AC administration in this population and its effect on overall survival (OS) for available patient, tumor, and treatment characteristics Methods: Using National Cancer Data Base, a cohort of 42,971 stage II CC patients diagnosed from 2004 to 2009, who underwent surgery with curative intent, was identified. Chi-square test and multivariate logistic regression were used to analyze baseline characteristics and to calculate odds of chemotherapy administration, respectively. Survival analysis was conducted using Kaplan Meier survival analysis with log-rank test and Cox proportional hazards regression modeling. Results: AC was administered to 26% patients. The use decreased with advancing age and elderly patients received more single-agent than multi-agent chemotherapy (3 vs. 2.4%, p < 0.0001). Major predictors of AC use included pT4 status, evaluation of <12 lymph nodes, high grade tumors, positive resection margins, age <65 years, left sided tumors, and low comorbidity score. AC was associated with improved OS regardless of high-risk features (pT4, undifferentiated histology, <12 lymph node evaluation, or positive resection margins), tumor location, age, gender, comorbidity index, chemotherapy regimen or type of colectomy (adjusted HR: single-agent 0.55, multi-agent 0.6; p < 0.0001). In subgroup analysis, AC use compensated for the survival differences otherwise seen between left and right sided tumors in the non-chemotherapy population. Conclusion: AC in stage II CC was associated with improved OS regardless of age, chemotherapy type or high-risk features. It improved 5-years OS irrespective of tumor location and seemed to compensate for the survival difference seen between right and left sided tumors noted in the non-chemotherapy group.

Age-dependent overall survival benefit of androgen deprivation therapy for metastatic prostate cancer.

BACKGROUND: Androgen deprivation therapy (ADT) remains a standard of care in metastatic prostate cancer. Recent prospective trials have explored addition of chemotherapy to ADT. We retrospectively examined overall survival in metastatic prostate cancer patients treated with ADT, chemotherapy plus ADT (C + ADT), or observation from 2004 to 2010 using National Cancer Database data. METHODS: Using the National Cancer Database, 21,977 patients with metastatic prostate cancer diagnosed from 2004 to 2010 were identified. Multivariate logistic regression, Kaplan-Meier survival analysis and Cox proportional hazards regression modeling were implemented, with overall survival as the primary endpoint. RESULTS: Five-year overall survival was 13.6% in patients aged ≥ 75 years vs. 30.1% (age 65-74) and 34.5% (age 18-64). Subgroup analysis of age-based cohorts (<65 and ≥65 years) showed poor overall survival for C + ADT vs. ADT alone, both in younger (HR 1.35, 95% CI 1.21-1.50; p < 0.0001) as well as older (HR 1.21, 95% CI 1.08-1.34; p = 0.0006) populations. Younger patients had no significant difference in overall survival for observation vs. ADT (HR 0.99, 95% CI 0.92-1.08; p = 0.9121). Besides age, other factors impacting overall survival included race, rural/urban settings, comorbidity score, income, PSA and radiation. DISCUSSION: Younger patients had no significant difference in overall survival between observation or ADT. This implies a group of younger patients in whom ADT does not confer any overall survival benefit. Future clinical trials with genetic and biologic markers are needed to delineate which subgroups would not benefit from C + ADT or ADT alone. This is of utmost clinical importance given the negative impact of ADT on quality of life and comorbidities.

Trends in Incidence and Factors Affecting Survival of Patients With Cholangiocarcinoma in the United States.

Background: Cholangiocarcinoma (CCA) includes cancers arising from the intrahepatic and extrahepatic bile ducts. The etiology and pathogenesis of CCA remain poorly understood. This is the first study investigating both incidence patterns of CCA from 1973 through 2012 and demographic, clinical, and treatment variables affecting survival of patients with CCA. Patients and Methods: Using the SEER database, age-adjusted incidence rates were evaluated from 1973-2012 using SEER*Stat software. A retrospective cohort of 26,994 patients diagnosed with CCA from 1973-2008 was identified for survival analysis. Cox proportional hazards models were used to perform multivariate survival analysis. Results: Overall incidence of CCA increased by 65% from 1973-2012. Extrahepatic CCA (ECC) remained more common than intrahepatic CCA (ICC), whereas the incidence rates for ICC increased by 350% compared with a 20% increase seen with ECC. Men belonging to non-African American and non-Caucasian ethnicities had the highest incidence rates of CCA. This trend persisted throughout the study period, although African Americans and Caucasians saw 50% and 59% increases in incidence rates, respectively, compared with a 9% increase among other races. Median overall survival (OS) was 8 months in patients with ECC compared with 4 months in those with ICC. Our survival analysis found Hispanic women to have the best 5-year survival outcome (P<.0001). OS diminished with age (P<.0001), and ECC had better survival outcomes compared with ICC (P<.0001). Patients who were married, were nonsmokers, belonged to a higher income class, and underwent surgery had better survival outcomes compared with others (P<.0001). Conclusions: This is the most up-to-date study of CCA from the SEER registry that shows temporal patterns of increasing incidence of CCA across different races, sexes, and ethnicities. We identified age, sex, race, marital status, income, smoking status, anatomic location of CCA, tumor grade, tumor stage, radiation, and surgery as independent prognostic factors for OS in patients with CCA.

Combined checkpoint inhibitor therapy causing diabetic ketoacidosis in metastatic melanoma.

BACKGROUND: There has been a significant improvement in survival of advanced malignancies with the advent of checkpoint inhibitors. These newer treatment modalities come with a wide spectrum of unique side effects, termed immune related adverse events (irAE), ranging from mild skin rash to severe colitis. Included in that spectrum is the rare side effect of autoimmune diabetes mellitus. Despite a few case reports illustrating the incidence of autoimmune diabetes associated with immunotherapy, there has not been much mentioned about exacerbation or acceleration of hyperglycemia in non-autoimmune settings leading to de novo diagnosis of type 2 diabetes mellitus. CASE PRESENTATION: We report the case of a 42 year old man with metastatic melanoma and no prior history of diabetes mellitus, who presented with diabetic ketoacidosis (DKA) after 3 cycles of combination checkpoint inhibitor therapy using nivolumab and ipilimumab. New onset diabetes mellitus was diagnosed on the basis of elevated hemoglobin A1c, in the absence of prior personal or family history. Autoimmune or type 1 diabetes mellitus was ruled out with normal levels of anti-glutamic acid decarboxylase 65 (GAD65) antibody, zinc transporter 8 (ZnT8) antibody, and islet antigen-2 (IA-2) antibody. CONCLUSIONS: This case report highlights the importance of recognizing rare but serious adverse events related to immunotherapy and incorporation of appropriate tools for early identification and management in national cancer treatment guidelines.