Maki Umemiya

Comparison of nedaplatin and cisplatin in concurrent chemoradiotherapy for cervical cancer: a systematic review and meta-analysis

Abstract Background Cisplatin-based concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer; however, its nephrotoxicity and gastrointestinal toxicity often limit treatment eligibility and completion. Nedaplatin, a cisplatin analogue with reduced renal and gastrointestinal toxicity, has been increasingly used in East Asia, but its comparative efficacy and safety in cervical cancer have not been comprehensively evaluated. Methods We systematically searched MEDLINE, Embase, CENTRAL, CNKI, Ichushi Web, ICTRP, and ClinicalTrials.gov for randomized controlled trials comparing nedaplatin versus cisplatin-based CCRT. The primary efficacy outcome was all-cause mortality at 3 years, and the primary safety outcome was renal toxicity. Secondary outcomes included mortality at 1 and 5 years, progression or mortality, hematologic and gastrointestinal toxicities, liver dysfunction, and quality of life. Random-effects meta-analyses were performed using risk ratios. Results Seventeen trials met the eligibility criteria. All-cause mortality at 3 years did not differ significantly between the groups (RR 0.88; 95% CI 0.51–1.51; I 2  = 0%). Nedaplatin significantly reduced renal toxicity (RR 0.25; 95% CI 0.20–0.31; I 2  = 0%). Short-term outcomes favored nedaplatin, including lower 1 year mortality (RR 0.61; 95% CI 0.40–0.93) and fewer 1 year progression or mortality events (RR 0.63; 95% CI 0.44–0.91). The incidences of anemia and severe nausea/vomiting were also lower with nedaplatin. No eligible study assessed quality of life. Conclusion Nedaplatin showed fewer adverse effects and comparable or improved short-term outcomes compared with cisplatin. These findings support nedaplatin as a potential alternative for patients who are cisplatin-intolerant or frail. Confirmation in large, high-quality trials with long-term follow-up and patient-reported outcomes is warranted.

Possible overestimation of treatment effects of pelvic and para-aortic lymphadenectomy for early-stage ovarian clear cell carcinoma: a retrospective propensity-score weighted multi-center cohort study

The treatment effects of lymphadenectomy in early-stage ovarian clear cell carcinoma (OCCC) reported in previous studies may have been overestimated owing to confounding factors. This study aimed to investigate the treatment effect of pelvic and para-aortic lymphadenectomy (PeNPAN) in early-stage OCCC, with careful adjustment for potential confounders. This retrospective multi-center cohort study involved women with preoperatively suspected stage I OCCC. We included patients who underwent surgery for OCCC between 2005 and 2019 at 11 affiliated institutions. The exposure (PeNPAN) group comprised patients who underwent PeNPAN. The primary outcome was disease-free survival (DFS). Additionally, hazard ratios (HRs) of lymphadenectomy for DFS were estimated using unadjusted and propensity score-weighted Cox regression models and biased models applied in previous studies. To identify strong confounders, we further examined factors associated with recurrence that differed between the groups. We analyzed 304 women who underwent surgery for preoperatively suspected stage I OCCC. The unadjusted HR for DFS was 0.63 (95% confidence interval [CI]=0.36-1.09; p=0.10), and the propensity-score adjusted HR was 0.82 (95% CI=0.42-1.58; p=0.55). The biased model showed a statistically significant HR of 0.59 (95% CI=0.36-1.00; p=0.048). Adhesions in the Douglas' pouch and cardiovascular disease were associated with recurrence and were more prevalent in the control group, suggesting potential confounders. After adjusting for potential confounders, the observed treatment effects of lymphadenectomy in the biased models were no longer statistically significant. Future investigations should carefully account for possible confounders, including intraoperative adhesions and comorbidities.