A phase I study was performed to determine the recommended dose of carbon ion radiotherapy and 3D image-guided brachytherapy for histologically confirmed stage II (≥4 cm), III, or IVA cervical cancer. Dose-limiting toxicities (treatment-related toxicities occurring within three months from the start of carbon ion radiotherapy) included Grade 3 non-hematological toxicity, Grade 4 hematological toxicity, or interruption of treatment for more than two weeks due to treatment-related toxicities. Carbon ion radiotherapy consisted of whole-pelvic irradiation with 36.0 Gy (relative biological effectiveness) in 12 fractions and local boost with 19.2 Gy in four fractions for the primary site, and for positive lymph nodes. Three sessions of three-dimensional (3D) image-guided brachytherapy were administered after completion of carbon ion radiotherapy. Weekly cisplatin at a dose of 40 mg/m² was given concurrently. At a dose level of one, a total rectosigmoid D2cc dose between 67.2 Gy and 71.3 Gy at a biological equivalent dose of 2 Gy per fraction from carbon ion radiotherapy and 3D image-guided brachytherapy was prescribed. Six patients were enrolled into this dose level. No patients developed the pre-defined dose-limiting toxicities. For late toxicities, however, one patient developed Grade 3 rectal hemorrhage requiring transfusion at 10 months after treatment. The median survival time was 50.0 months for the five surviving patients. No further dose escalation was performed, and we determined the dose of level one as the recommended rectosigmoid dose. Although our results are preliminary, the study regimen encourages further investigation (registration: UMIN000013340).

Endometriosis-associated ovarian malignancies have been well documented. Although these malignancies also occur as extraovarian lesions, little is known about them. Thus, this literature review aimed to further explore these rarely experienced tumors. A total of 257 published cases between April 1990 and April 2020 were found using PubMed, and 212 cases were included in the analysis considering Sampson’s criteria and the history of endometriosis. We classified these cases as follows: intestine, abdominal scar, vagina and vulva, peritoneum and deep endometriosis, urinary tract, uterine cervix, and others. Age of patients, history of endometriosis, types of past hormonal therapy, symptoms, histological types, and treatment were identified. The most common tumor site was the intestine. Endometrioid carcinoma was the dominant histological type. Contrary to the ovary, clear cell carcinoma was rare in extraovarian sites. On the other hand, clear cell carcinoma represented the largest number of abdominal scars. This difference may help us to understand the development of endometriosis-related malignancies. Hormonal treatment was mentioned in 67 cases and estrogen replacement therapy in 33 cases. Although risks of estrogen therapy are still controversial, the highly differentiated histological types and hormone-dependent characteristics of endometriosis-associated malignancy should be considered. Physicians should be careful about estrogen monotherapy after hysterectomy and long-term hormone replacement therapy in patients with a history of endometriosis.

Tate S, et al. J Gynecol Oncol. 2025 Mar;36:e80. https://doi.org/10.3802/jgo.2025.36.e80

Takahashi Y, et al. J Gynecol Oncol. 2024 Jan;35:e37. https://doi.org/10.3802/jgo.2024.35.e37

Objective: Endometrial cancer (EC) is one of the most common cancers in women, and its incidence is increasing worldwide. The prognosis of recurrent and advanced cancer remains poor because treatment options are limited. Ubiquitin C-terminal hydrolase-L1 (UCHL1) is associated with the progression of several cancers including EC. In this study, we analyzed the function of UCHL1 in EC progression. Methods: UCHL1 expression in the serum of patients with EC was measured using an enzyme-linked immunosorbent assay. Changes in cell migration and invasion were analyzed in UCHL1-overexpressing or UCHL1-knockdown cells (UCHL1-OE/UCHL1-KD) using wound-healing and transwell assays. Messenger RNA expression of epithelial–mesenchymal transition (EMT)-related genes in each cell was detected using quantitative real-time polymerase chain reaction (qRT-PCR). UCHL1 and EMT marker proteins were detected with Western blotting and an immunofluorescence assay (IFA). Results: Serum UCHL1 expression was significantly elevated in patients with metastases. Wound-healing assays and transwell assays showed that UCHL1 could promote cell migration and invasion. These effects were suppressed by UCHL1 knockdown and inhibition. UCHL1 overexpression modulated the expressions of EMT-related molecules in EC cells at the mRNA and protein levels. Furthermore, IFA analysis showed that changes in EMT-related molecules were consistent with lesions of UCHL1 expression. Conclusions: This study revealed that UCHL1 could contribute to promoting cell migration and invasion. These results may be associated with EMT regulation in EC cells.