Alessandra De Finis

Pattern of recurrence in endometrial cancer. The murderer always returns to the scene of the crime

Endometrial cancer recurrence occurs in about 18 % of patients. This study aims to analyze the pattern recurrence of endometrial cancer and the relationship between the initial site of primary disease and the relapse site in patients undergoing surgical treatment. We retrospectively reviewed all surgically treated patients with endometrial cancer selecting those with recurrence. We defined primary site disease as uterus, lymph nodes, or peritoneum according to pathology analysis of the surgical specimen. The site of recurrence was defined as vaginal cuff, lymph nodes, peritoneum, and parenchymatous organs. Our primary endpoint was to correlate the site of initial disease with the site of recurrence. The study enrolled 1416 patients. The overall recurrence rate was 17,5 % with 248 relapses included in the study. An increase of 9.9, 5.7, and 5.7 times in the odds of relapse on the lymph node, peritoneum, and abdominal parenchymatous sites respectively was observed in case of nodal initial disease (p < 0.001). A not significant difference in odds was observed in terms of vaginal cuff relapse (OR 0.9) between lymph node ad uterine primary disease (p = 0.78). An increasing OR of 8.7 times for nodal recurrences, 46.6 times for peritoneum, and 23.3 times for parenchymatous abdominal recurrences were found in the case of primary peritoneal disease (p < 0.001). Endometrial cancer tends to recur at the initial site of the disease. Intraoperative inspection of the adjacent sites of primary disease and targeted instrumental examination of the initial sites of disease during follow-up are strongly recommended.

Proton Beam Therapy in Gynecological Cancers: A Systematic Review of Indications, Complications, and Limitations

Background and Objectives: Gynecological cancers frequently require radiation therapy (RT) in primary, adjuvant, or salvage settings. However, photon-based RT is associated with non-negligible toxicity, and treatment of pelvic recurrences after prior irradiation remains challenging. Proton beam therapy (PBT), due to its favorable dose distribution and reduced exposure of organs at risk (OARs), has emerged as a potential alternative, particularly in re-irradiation scenarios. Despite its expanding use in other malignancies, evidence supporting PBT in gynecologic cancers remains limited. This systematic review aims to investigate the use of PBT in gynecological cancers and its associated complications. Materials and Methods: This systematic review was conducted according to PRISMA guidelines and registered in PROSPERO. A comprehensive search (2000–2025) identified studies investigating PBT in gynecologic cancers. Eligible designs included randomized trials and prospective and retrospective series. Reported adverse events were categorized as GI, GU, or other, and only grade ≥3 CT-CAE complications were considered. Results: Of 580 records screened, 9 studies comprising 232 patients met inclusion criteria. Most patients were treated for endometrial (n = 147) or cervical (n = 75) cancer; 90 received chemotherapy. Overall, severe toxicity occurred in 15.2% of patients. GI complications ranged from 0–14% and GU from 0–33%. Complication rates were lowest in adjuvant or de novo treatment series (0–10%), whereas re-irradiation cohorts showed higher rates (up to 33% GU). Comparative studies suggested a possible advantage of PBT over IMRT, particularly for GI toxicity, though data remain limited. Conclusions: Severe GI and GU toxicity after PBT in gynecologic cancers appears infrequent, particularly in primary and adjuvant settings, though re-irradiation remains challenging. Current evidence is restricted to small and heterogeneous studies. Ongoing phase II trials will provide prospective data to clarify feasibility, toxicity, and long-term outcomes. Until then, PBT in gynecologic oncology should be regarded as investigational.