XWL-5-11

We evaluated the role of total body irradiation (TBI) and its interaction with smoking in relation to subsequent lung cancer after blood or marrow transplantation (BMT) by leveraging the BMT Survivor Study. Participants included individuals who underwent BMT (1974-2014) at 3 centers and who survived ≥2 years. The impact of TBI and smoking was evaluated using Fine-Gray subdistribution hazard models. Standardized incidence ratios were calculated using age- and sex-specific incidence rates obtained from the Surveillance, Epidemiology, and End Results Program. Of the 6981 BMT survivors (median age, 46 years; 58.5% male), 113 developed subsequent lung cancer at a median of 7 years after BMT, representing a 40% higher risk when compared with the general population (95% confidence interval [CI], 1.2-1.7). In the subcohort with smoking data available (n = 3767), there was a significant TBI-smoking interaction (P< .0001). When compared with no TBI never smokers, the risk was increased among TBI-exposed ≥10-year smokers (adjusted subdistribution hazard ratio [asHR], 3.9; 95% CI, 3.0-8.9) and no TBI ≥10-year smokers (asHR, 3.0; 95% CI, 1.3-5.6). Among the <10-year smokers, the risk was not increased, regardless of TBI exposure (TBI: asHR, 1.4; 95% CI, 0.9-3.5; no TBI: asHR, 1.1; 95% CI, 0.30-4.3; reference: no TBI never smokers). TBI exposure in the absence of smoking did not increase the risk (asHR, 0.6; 95% CI, 0.2-1.7). Additional risk factors included older age at BMT, male sex, and pre-BMT exposure to anthracyclines and/or topoisomerase II inhibitors. These findings support personalized surveillance for BMT survivors at heightened risk for subsequent lung cancer.

Etoposide is a semisynthetic derivative of podophyllotoxin and an FDA‐approved topoisomerase II inhibitor that induces DNA strand breaks leading to cancer cell death. Cervical cancer remains the fourth most common cancer among women worldwide, with platinum‐based chemotherapy constituting the standard of care. Although etoposide has demonstrated broad anticancer activity, its role in cervical cancer therapy is considered secondary and is mainly explored in combination regimens.

This review summarizes published clinical and preclinical studies evaluating the use of etoposide in cervical cancer, both as monotherapy and in combination with other chemotherapeutic agents. Emphasis is placed on treatment regimens, disease stages, routes of administration, limitations, and emerging strategies aimed at improving therapeutic outcomes.

The etoposide has been administered orally or intravenously and has shown clinical benefit primarily when used in combination therapies, including cisplatin, topotecan, mitomycin, epirubicin, doxorubicin, vincristine, cyclophosphamide, bevacizumab, and adriamycin. Its application is mainly observed in FIGO stage IA2–IB2, as well as in recurrent or metastatic cervical cancer. However, platinum‐based regimens, particularly cisplatin or carboplatin combined with paclitaxel, topotecan, fluorouracil, or bevacizumab, remain superior in efficacy. Limitations such as drug resistance and systemic toxicity have restricted the widespread use of etoposide. Recent research has focused on nanocarriers, dual inhibitors, and polymeric implants to enhance its therapeutic index and reduce adverse effects.

While etoposide is an effective topoisomerase II inhibitor with proven anticancer activity, its role in cervical cancer remains adjunctive rather than primary. Combination‐based strategies and advanced drug‐delivery systems hold promise for improving its clinical utility. Continued research is essential to overcome resistance and toxicity, potentially expanding the therapeutic relevance of etoposide in cervical cancer management.