IS ADJUVANT CHEMOTHERAPY BENEFICIAL IN ELDERLY PATIENTS WITH STAGE III APPENDICEAL ADENOCARCINOMA?
Tracey Pu*1, Shadin Ghabra1, Joanna T. Swinarska2, Sarfraz R. Akmal1, Lily L. Nguyen3, Thuy B. Tran3, Andrew M. Blakely1, Oliver S. Eng3
1Surgical Oncology Program, National Cancer Institute, Bethesda, MD; 2Northwestern Memorial HealthCare Corp, Chicago, IL; 3University of California Irvine, Irvine, CA
Limited evidence exists regarding survival benefit of adjuvant chemotherapy for non-metastatic appendiceal adenocarcinoma patients, and many providers defer to colorectal adenocarcinoma guidelines for adjuvant therapy regimens. Decision-making regarding systemic therapy initiation is often based on nodal positivity, to which adequate staging is achieved via right hemicolectomy (RHC). However, treatment in the elderly patient population can present additional considerations given the potential morbidity of surgery and systemic therapy. We sought to analyze outcomes in elderly patients with node-positive appendiceal adenocarcinoma.
Patients diagnosed with Stage III appendiceal adenocarcinoma who underwent a RHC with 12 or more examined lymph nodes were identified using the National Cancer Database (2004-2019). Elderly patients were defined as patients with age of diagnosis greater than 65 years old, while Non-elderly patients were defined as patients with age of diagnosis 65 years or younger. Propensity score matching (PSM) was performed between elderly and non-elderly patients adjusting for gender, race, Charlson-Deyo Comorbidity Index (CCI), number of positive lymph nodes, and grade. Chi-squared testing, Kaplan-Meier method with log-rank test, and Cox proportional hazards regression models were employed.
1475 patients were identified, with 58.2% (858) elderly patients and 41.8% (617) non-elderly patients. Elderly patients were more likely to present with a CCI ≥ 2 (9.7% v. 3.8%, p<0.001). Tumor grade or mucinous histology were similar between the groups. Elderly patients were less likely to receive chemotherapy (68.6% v. 85.3%, p<0.001) or multi-agent chemotherapy (48.4% v. 74.3%, p<0.001). On unadjusted Kaplan Meier analyses, elderly patients receiving single-agent chemotherapy had similar median survival (54.1 mo, 95% CI 11.5-31.6) compared to multi-agent (59.8 mo, 95% CI 49.0-70.6), while both conferred survival advantage compared to no chemotherapy (19.4 mo, 95% CI 13.0-25.7) (Figure 1A). On multivariate analyses after PSM, single-agent (HR 0.46) and multi-agent (HR 0.41) chemotherapy regimens conferred a survival advantage compared to elderly patients who did not receive chemotherapy. There was no survival advantage between single-agent versus multi-agent (p=0.55). Greater than 3 positive lymph nodes (HR 1.73) and grade (Grade 2 HR 2.32, Grade 3 HR 2.90, Grade 4 HR 4.02) were associated with decreased survival.
Elderly patients presenting with stage III appendiceal adenocarcinoma confer a survival benefit from adjuvant chemotherapy after right hemicolectomy, regardless of histological grade or CCI score. However, multiagent chemotherapeutic regimens demonstrate a diminished survival advantage, and toxicities of these regimens may outweigh benefit in elderly patients.
FIGURE 1. Kaplan Meier survival curves of Elderly (A) and Non-Elderly (B) appendiceal adenocarcinoma patients stratified by adjuvant chemotherapeutic regimens
TABLE 1. Cox regression multivariable analysis of factors affecting survival after propensity score matching for elderly appendiceal adenocarcinoma patients
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