Zheng Feng

Germline Mutational Landscape and Novel Targetable RAD51D Variant in Chinese Patients With Ovarian Cancer

PURPOSE Genetic variants of ovarian cancer (OV) show ethnic differences, but data from the Chinese population are still insufficient. Here, we elucidate the inheritance landscape in Chinese patients with OV and examine the functional implications of a Chinese-enriched RAD51D variant. METHODS Between 2015 and 2018, 373 consecutive patients with OV were prospectively enrolled. Variants of BRCA1/2, other homologous recombination repair (HRR) genes, and DNA mismatch repair (MMR) genes were analyzed using next-generation sequencing. An enriched RAD51D variant was identified, and its functional effects were examined using Cell Counting Kit-8, colony formation, transwell migration, and drug sensitivity assays. RESULTS Overall, 31.1% (116/373) of patients had at least one pathogenic or likely pathogenic germline variant. BRCA1 and BRCA2 accounted for 16.09% and 5.36%, respectively, with one patient having both variants. In addition, 32 (8.58%) patients carried other HRR gene variants, whereas three (0.8%) patients had MMR gene variants. The RAD51D variant ranked third (8/373, 2.1%), and its rate was much higher than that in other populations. Remarkably, all eight patients harbored the RAD51D K91fs variant (c.270_271dup, p.Lys91Ilefs*13) and demonstrated satisfactory platinum response and favorable prognosis. This variant confers enhanced sensitivity to poly (ADP-ribose) polymerase inhibitors in OV cells. However, the effects on platinum sensitivity were inconsistent across different cell lines. Against the background of the TP53 variant, RAD51D K91fs variant showed increased sensitivity to cisplatin. CONCLUSION Our study revealed the inheritance landscape of OV and identified an enriched RAD51D variant in Chinese patients with OV. This can serve as an important reference for OV management and a potential therapeutic target.

Management for perioperative complications of diaphragmatic surgery in ovarian cancer at a Chinese tertiary cancer center

Diaphragm is the common site of metastasis in advanced ovarian cancer. Diaphragmatic surgery is necessary to achieve complete resection. Relative complications also pose challenges to perioperative management. This study aims to explore the influencing factors and management strategies for perioperative complications of diaphragm surgery. This study retrospectively included 396 patients who underwent diaphragmatic surgery for advanced ovarian cancer at Fudan University Shanghai Cancer Center from July 2015 to June 2022. Diaphragm surgical methods were classified, and perioperative complications were regarded according to Memorial Sloan Kettering Cancer Center criteria. Clinical characteristics and perioperative complications were analyzed to find correlations to establish the nomogram. Among the 396 patients, 163 patients (41.2%) suffered from perioperative complications. Pleural effusion (33.1%) and pneumothorax (5.3%) were the most commonly reported. Patients with longer surgery duration (>3 hours) (p=0.003) and who underwent diaphragmatic incision surgery (p=0.004) had a higher incidence of postoperative complications. The incidence of postoperative pleural effusion was significantly higher in patients who underwent diaphragm full-thickness resection (49.3%) than diaphragmatic stripping (29.5%) (p=0.001), and patients who underwent diaphragm full-thickness resection are more likely to require drainage (p=0.001). Multi-variate analyses showed that stage IV tumor, long operation time, and diaphragm full-thickness resection are associated with postoperative pleural effusion. Pleural effusion is the most common complication of diaphragmatic surgery in patients with ovarian cancer. Routine placement of prophylactic chest tubes is not appropriate for all patients undergoing diaphragmatic surgery. Our nomogram could help to predict its risk and indicate prophylactic management.

Optimal adjuvant radiotherapy strategy for cervical cancer: a multi-center database cohort study

This study aimed to explore the prognostic impact of different post-operative radiotherapy patterns in cervical cancer and identify an optimal treatment strategy using a multi-center database. This cohort was derived from the Standardized Cervical Cancer-Specific Database, and enrolled patients with clinical International Federation of Gynecology and Obstetrics stage IB1 to IIA2 undergoing radical hysterectomy and adjuvant radiation therapy, concurrent chemoradiation, or sequential chemoradiotherapy between 2019 and 2023. Patients were stratified into high-risk and intermediate-risk groups. Kaplan-Meier curves and Cox proportional hazards model regression analyses were performed to identify potential prognostic factors. Propensity score matching was subsequently applied to balance relevant covariates. A total of 1436 patients were identified (radiation therapy: 308; concurrent chemoradiation: 950; sequential chemoradiotherapy: 178) with a median follow-up of 32 months (range; 10.3-72.9). Among high-risk patients, concurrent chemoradiation showed superior 3-year progression-free survival (94.1%) versus sequential chemoradiotherapy (87.4%) or radiation therapy (83.4%, p = .014), but no significant overall survival difference was observed (concurrent chemoradiation: 88.5%; sequential chemoradiotherapy: 82.0%; radiation therapy: 77.3%, p = .07). For intermediate-risk patients, radiation therapy and concurrent chemoradiation exhibited better 3-year progression-free survival than sequential chemoradiotherapy (radiation therapy: 97.9%; concurrent chemoradiation: 96.3%; sequential chemoradiotherapy: 90.8%, p = .0019), with comparable overall survival (radiation therapy: 96.9%; concurrent chemoradiation: 95.3%; sequential chemoradiotherapy: 89.1%, p = .37). Post-matching, concurrent chemoradiation retained progression-free survival superiority in high-risk patients compared with sequential chemoradiotherapy (96.1% vs 88.9%, p = .044), whereas no progression-free survival (radiation therapy: 97.5%; concurrent chemoradiation: 94.3%, p = .22) or overall survival (radiation therapy: 96.3%; concurrent chemoradiation: 96.4%, p = .52) differences emerged between radiation therapy and concurrent chemoradiation in intermediate-risk patients. This cohort study demonstrates that concurrent chemoradiation may be considered a preferred approach for high-risk populations, whereas adding chemotherapy to radiation therapy could not improve prognosis for intermediate-risk patients.