Re-administration of platinum-based chemotherapy for recurrent endometrial cancer: an ancillary analysis of the SGSG-012/GOTIC-004/Intergroup study.

BACKGROUND: We previously demonstrated the applicability of the concept of "platinum sensitivity" in recurrent endometrial cancer. Although immune checkpoint inhibitors have been widely incorporated into endometrial cancer treatment, the debate continues regarding treatment options in patients with recurrent endometrial cancer who have previously received platinum-based chemotherapy. In this study, we assessed the duration of response to secondary platinum-based treatment using pooled data from the SGSG-012/GOTIC-004/Intergroup study. METHODS: Among the 279 participants in the SGSG-012/GOTIC-004/Intergroup study wherein platinum-based chemotherapy was re-administered for managing recurrent endometrial cancer between January 2005 and December 2009, 130 (47%) responded to chemotherapy. We compared the relationship between platinum-free interval and duration of secondary platinum-based treatment using pooled data. RESULTS: In 40 patients (31%), the duration of response to secondary platinum-based treatment exceeded the platinum-free interval. The duration of response to secondary platinum-based treatment exceeded 12 months in 51 patients (39%) [platinum-free interval: < 12 months, 14/48 (29%); 12-23 months, 18/43 (42%); 24-35 months, 8/19 (42%); ≥ 36 months, 11/20 (55%)]. In particular, in eight patients (6%), the duration of response to secondary platinum-based treatment exceeded 36 months [platinum-free interval: < 12 months, 3/48 (6%); 12-23 months, 0/19 (0%); 24-35 months, 2/19 (11%); ≥ 36 months, 3/20 (15%)]. CONCLUSIONS: Re-administration of platinum-based chemotherapy for recurrent endometrial cancer may result in a long-term response exceeding the platinum-free interval in some patients. Even in the current situation, where immune checkpoint inhibitors have been introduced, re-administration of platinum-based chemotherapy is worth considering.

2α-Substituted Vitamin D Derivatives Effectively Enhance the Osteoblast Differentiation of Dedifferentiated Fat Cells.

The active form of vitamin D3, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], is a principal regulator of calcium homeostasis through activation of the vitamin D receptor (VDR). Previous studies have shown that 2α-(3-hydroxypropyl)-1,25D3 (O1C3) and 2α-(3-hydroxypropoxy)-1,25D3 (O2C3), vitamin D derivatives resistant to inactivation enzymes, can activate VDR, induce leukemic cell differentiation, and increase blood calcium levels in rats more effectively than 1,25(OH)2D3. In this study, to further investigate the usefulness of 2α-substituted vitamin D derivatives, we examined the effects of O2C3, O1C3, and their derivatives on VDR activity in cells and mouse tissues and on osteoblast differentiation of dedifferentiated fat (DFAT) cells, a cell type with potential therapeutic application in regenerative medicine. In cell culture experiments using kidney-derived HEK293 cells, intestinal mucosa-derived CaCO2 cells, and osteoblast-derived MG63 cells, and in mouse experiments, O2C2, O2C3, O1C3, and O1C4 had a weaker effect than or equivalent effect to 1,25(OH)2D3 in VDR transactivation and induction of the VDR target gene CYP24A1, but they enhanced osteoblast differentiation in DFAT cells equally to or more effectively than 1,25(OH)2D3. In long-term treatment with the compound without the medium change (7 days), the derivatives enhanced osteoblast differentiation more effectively than 1,25(OH)2D3. O2C3 and O1C3 were more stable than 1,25(OH)2D3 in DFAT cell culture. These results indicate that 2α-substituted vitamin D derivatives, such as inactivation-resistant O2C3 and O1C3, are more effective than 1,25(OH)2D3 in osteoblast differentiation of DFAT cells, suggesting potential roles in regenerative medicine with DFAT cells and other multipotent cells.

A case of low-grade endometrial stromal sarcoma presented as an intramyometrial mass mimicking uterine leiomyoma on MRI.

A low-grade endometrial stromal sarcoma (ESS) has a pattern of presenting as an intramyometrial mass and is often misdiagnosed as cellular leiomyoma or degenerative uterine leiomyoma. A low-grade ESS is a malignant tumour that requires total hysterectomy with bilateral salpingo-oophorectomy; while a leiomyoma is a benign tumour and could be acceptable for enucleation. As the treatment strategies differ between a low-grade ESS and leiomyoma, radiologists should be familiar with the characteristic MRI findings of a low-grade ESS. A 51-year-old woman with abnormal uterine bleeding had been observed for 2 years at a previous hospital for a uterine leiomyoma based on MRI findings. A contrast-enhanced MRI demonstrated an intramyometrial mass composed of three components with the hypointense rim on T2-weighted images (T2WI): the first component was a homogeneous solid structure with mild hyperintensity on T2WI with a low apparent diffusion coefficient value; the second component was cystic; the third component was a structure of low signal intensity on T2WI similar to the muscle. Although a degenerative uterine leiomyoma was a differential diagnosis, these MRI findings were suggestive of a low-grade ESS. A total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic lymphadenectomy, and partial omentectomy were performed. The pathological diagnosis was a low-grade ESS. In a low-grade ESS, there are three major patterns of MRI findings: one of these patterns is the less popular but clinically important intramyometrial mass pattern, which can be misdiagnosed as a leiomyoma, and this case conformed to this pattern.

Prevention of symptomatic pulmonary embolism for gynecologic malignancies with preoperative asymptomatic venous thromboembolism: GOTIC-VTE trial.

OBJECTIVE: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. METHODS: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. RESULTS: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82 patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). CONCLUSION: The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE. TRIAL REGISTRATION: JRCT Identifier: jRCTs031180124.

Combination treatment with paclitaxel, carboplatin and cetuximab in maxillary sinus cancer: A case report.

The standard treatment for maxillary sinus cancer is surgery; however, surgery for advanced cases often leads to significant aesthetic and functional disability. Combination treatment (induction chemotherapy) with paclitaxel, carboplatin and cetuximab (PCE) can be effective in head and neck cancer. The present study describes the case of a patient with advanced maxillary sinus cancer that was successfully treated using the PCE regimen. A 69-year-old man presented to the Department of Dentistry and Oral Surgery, Hokuto Hospital (Obihiro, Japan) with left buccal swelling and an irregular mass on the left maxillary gingiva. The lesion filled the ethmoid and maxillary sinus, and destroyed the pterygoid process. Numerous lymph node metastases were suspected in the bilateral cervical region. The patient was diagnosed with left maxillary sinus cancer T4aN2cM0 and treated with PCE. The size of the tumor was markedly reduced after the initial treatment. After six cycles of PCE, bioradiotherapy (BRT; 66 Gy/33 Fr) was performed for the remaining lesion, and a complete response was achieved. Ten months after BRT, the tumor recurred in the anterior wall of the left maxillary sinus, which was treated by partial maxillary resection and split-thickness skin grafting. No local or cervical recurrence was observed 2 years after the surgery. These findings suggested that PCE could be considered as the first step for the treatment of highly advanced malignant tumors in the head and neck.