Long-term follow-up of efficacy and safety of selinexor maintenance treatment in patients with TP53wt advanced or recurrent endometrial cancer: A subgroup analysis of the ENGOT-EN5/GOG-3055/SIENDO study.

OBJECTIVE: To report long-term efficacy and safety of selinexor maintenance therapy in adults with TP53 wild-type (TP53wt) stage IV or recurrent endometrial cancer (EC) who achieved partial remission (PR) or complete remission (CR) following chemotherapy. METHODS: Analysis of the prespecified, exploratory subgroup of patients with TP53wt EC from the phase 3 SIENDO study was performed. Progression-free survival (PFS) benefit in patients with TP53wt EC and across other patient subgroups were exploratory endpoints. Safety and tolerability were also assessed. RESULTS: Of the 263 patients enrolled in the SIENDO trial, 113 patients had TP53wt EC; 70/113 (61.9%) had TP53wt/proficient mismatch repair (pMMR) EC, and 29/113 (25.7%) had TP53wt/deficient mismatch repair (dMMR) EC. As of April 1, 2024, the median PFS (mPFS) for TP53wt patients who received selinexor compared with placebo was 28.4 versus 5.2 months (36.8-month follow-up, HR 0.44; 95% CI 0.27-0.73). A benefit in mPFS was seen with selinexor versus placebo regardless of MMR status (patients with TP53wt/pMMR EC: 39.5 vs 4.9 months, HR 0.36; 95% CI 0.19-0.71; patients with TP53wt/dMMR EC: 13.1 vs 3.7 months, HR 0.49; 95% CI 0.18-1.34). Selinexor treatment was generally manageable, with no new safety signals identified. CONCLUSION: In the phase 3 SIENDO study, selinexor maintenance therapy showed a promising efficacy signal and a manageable safety profile in the prespecified subgroup of patients with TP53wt EC who achieved a PR or CR following chemotherapy. These results are being further evaluated in an ongoing randomized phase 3 trial (NCT05611931).

Circulating tumor cells in patients with cervical cancer undergoing chemoradiotherapy combined with brachytherapy.

Circulating tumor cells (CTCs) have significant potential to become an important tool for monitoring the effects of treatment in solid tumors. The present study reports the occurance of CTCs in cervical cancer (CC) patients during radical chemoradiotherapy (CRT), including brachytherapy (BRT), and during the follow-up period. Patients diagnosed with CC treated with radical CRT were included in the study (n=30). A total of 167 CTC-tests (MetaCell®) were provided at predefined testing time points during the study follow-up (e.g., before CRT, after CRT, every three months of follow-up). In parallel with CTC-testing, SCC-Ag were measured to compare their predictive values during treatment. CTCs were present in 96% (25/26) of patients at the time of diagnosis and in 61% (14/23) after treatment. Patients who relapsed during the 36-month follow-up (n=10) showed an elevation in pre-treatment CTC- numbers, similarly there was a significant increase in pre-treatment SCC-Ag. As next, an increased number of CTCs was observed approximately 12 weeks before relapse was diagnosed by standard imaging modalities (MRI, US, PET-CT) in 3 of 4 patients. In addition to standardized vital cytomorphology of enriched CTCs, quantitative PCR (qPCR) was used to inform the nature of CTCs before treatment. Analysis revealed increased SOX2 and POUSF expression in CTCs in the group of patients with recurrence (P < 0.02). Disease aggressiveness may be related to increased expression of stem cell markers, as found in samples from relapsed patients. CTCs may be an aid to assess tumor burden and disease aggressiveness. An increase in CTCs precedes an increase in SCC-Ag and confirmation of relapse by imaging, as shown in our study.

Radiation-Related Fractures after Radical Radiotherapy for Cervical and Endometrial Cancers: Are There Any Differences?

In this study, we reviewed CT/MRI scans and studied the rates of radiation-related fractures in subjects treated for cervical cancer (CC, 63 subjects) by radical radiotherapy (RT) and in subjects treated for endometrial cancer (EC, 64 subjects) by radical surgery and RT. The differences between bone density measured in L1 on pretreatment CT, age and body mass index (BMI) were evaluated. Despite significant differences in RT total dose, age, BMI, etc., between both groups, the rate of radiation-related fractures was similar: 28.6% of CC versus 26.6% of EC subjects. CC subjects with fractures were significantly older (62.4 ± 10.1 vs. 49.0 ± 12.4 years; p < 0.001), and their bone densities were significantly lower (106.3 ± 40.0 vs. 168.2 ± 49.5 HU; p < 0.001); no difference in BMI was found. EC subjects with fractures were without significant difference in age but had significantly lower bone densities (103.8 ± 29.0 vs. 133.8 ± 42.3 HU; p = 0.009) and BMIs (26.1 ± 4.9 vs. 31.8 ± 6.9 kg/m2; p = 0.003). Bone density strongly correlated with age (r = -0.755) only in CC subjects. Subjects with fractures from both groups had similarly low bone densities (106.3 ± 40.0 vs. 103.8 ± 29.0 HU; p = 0.829); however, no correlation between bone density and BMI was found. The rate of radiation-related fractures in both groups was clearly associated only with low pretreatment bone density, reflecting osteoporosis.

Late Radiation-Related Toxicities in Patients Treated for Early-Stage Cervical Carcinoma by Surgery and Adjuvant Radiotherapy: A Retrospective Imaging Study.

Surgical treatment is preferred therapy of early-stage cervical carcinoma. In the risk of cancer recurrence surgery is often followed by adjuvant radiotherapy. In our retrospective study we aimed at identifying late (≥6 months) and very late (≥5 years) radiation adverse effects on imaging scans as CT, PET/CT and MRI in patients who underwent successful treatment for cervical carcinoma by radical surgery combined with radiotherapy ± chemotherapy. We correlated imaging results with clinical manifestations. We selected young and middle-aged patients with long life expectancy, as late radiation-related toxicities may significantly affect their quality of life. Patients were selected from those who were primary diagnosed and treated between the years 1987-2011 and regularly visited our Oncology department in years 2011-2012. Following inclusion criteria were applied: age ≤55 years at diagnosis, clinical follow-up ≥5 years and at least one tomography scan ≥3 years after finished treatment. One hundred and three subjects were reviewed: 73 patients met all inclusion criteria, while 30 patients fulfilled the inclusion criteria except for available tomography scan ≥3 years after therapy. The mean imaging follow-up was 11.2 ± 7.6 years and the mean clinical follow-up was 15.0 ± 6.9 years. In 20 (27%) subjects 27 cases grade I radiation-related toxicities were found; 9 (33%) of those 27 cases were clinically silent. In 14 (19%) females only grade I toxicities were observed. Grade III-IV toxicities were found in 5 (6.8%) subjects. No grade V toxicities were observed. We concluded that severe late side effects caused by radiotherapy were exceedingly rare in females successfully treated for early-stage cervical carcinoma, only 1 bilateral osteonecrosis, 2 cases of ileus, and 2 potentially radiation-induced tumors were found. The majority of radiation-related comorbidities found on imaging scans were clinically silent.