Alexandra Charalampopoulou

Quality of radiation shapes survival, invasiveness, and migration in ovarian cancer cell lines with different molecular profiles and varying alpha/beta ratios: an in vitro study on behalf of the Multicenter Italian Trials in Ovarian Cancer (MITO) group

The results of radiotherapy (RT) in oligometastatic ovarian cancers (OCs) lead to the query whether it is possible to stratify patients based on tumor hallmarks to ensure the best-personalized RT treatment. To address this question, we designed a preclinical study to evaluate the effects of high and low linear energy transfer (LET) radiation while considering molecular features and alpha/beta ratios of different OC cell lines. Exponentially growing human OVSAHO, OVCAR8, COV362, and OVCAR3 cells cultured in T-25 and T-75 flasks were exposed to different single physical doses of photons, protons, and carbon ion (CIRT) irradiation. We assessed ovarian cells' in vitro response using clonogenic survival (fitted using LQ model), migration by Boyden chamber assay, and invasion through BioCoat Matrigel invasion assay. Following photon irradiation, OVCAR3 was the most radioresistant and OVCAR8 the most radiosensitive cell line. OC cell migration decreased in a dose-dependent manner after irradiation, with CIRT showing the strongest effect, evident by the α/β ratio. The number of invading cells decreased following irradiation with all types. However, the greatest reduction was seen in CIRT, particularly at higher α/β ratios. Proton irradiation demonstrated similar potential to photons but did not match the effects of carbon ions in terms of survival, migration, and invasion

Particle Beam Re-irradiation in Oligo Recurrent Gynecological Malignancies

This study aimed to evaluate the efficacy and safety of proton beam radiotherapy (PBRT) and carbon ion radiotherapy (CIRT) as salvage treatments for oligorecurrent gynecological cancers. A retrospective analysis was performed on consecutive patients treated with PBRT or CIRT for recurrent gynecological tumors. The primary endpoints included the objective response rate (ORR) as well as 1- and 2-year local control (LC) survival rates. Toxicity was assessed as a secondary endpoint and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) 5.0 scale. Actuarial outcomes were evaluated using the Kaplan-Meier method, and predictors were identified with the Log-rank test. A total of 27 patients (median age: 64.5 years; IQR = 56.0, 69.0) with 28 recurrent lesions were treated with either PBRT (N = 12) or CIRT (N = 16), without concurrent systemic therapies. The majority of patients were treated for recurrences of cervical cancer (N = 8, 29%), endometrial cancer (N = 7, 25%), and ovarian cancer (N = 6, 21%). The most frequent site of recurrence was lymph nodes (N = 14, 50%). Lesions treated with CIRT had a larger volume (median volume 118 [IQR = 66, 233.5] vs. 99 [IQR = 54, 152.3]) and lower alpha/beta ratios (median = 3.8 [IQR = 3.5, 4.5] vs. 7.3 [IQR = 3.5, 10.0]). The overall ORR was 68% within 6 months and did not significantly vary between the groups (p = 0.687). The 1- and 2-year LC rates were 100% and 100% for PBRT, compared to 83% and 62% for CIRT (p = 0.075). Larger lesion volumes (p = 0.035) and failure to achieve an ORR (p = 0.009) were associated with worse LC outcomes, while lymph node recurrences (p = 0.052) and lower alpha/beta ratios (p = 0.078) were potentially linked to better LC. Both treatments were well tolerated, with no grade ≥3 toxicities observed. PBRT and/or CIRT appeared as an effective and safe option for recurrent gynecological cancers in a real-world setting. Larger cohorts and longer follow-up are needed for further validation and refining patient selection.