Rechallenge with Anti-PD-1 Inhibitors in Patients with Recurrent Gynecologic Malignancies.

PURPOSE: We investigated the treatment outcomes of immune checkpoint inhibitor (ICI) rechallenge in patients with recurrent gynecologic cancers. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 20 patients who underwent rechallenge with PD-1 inhibitors for recurrent gynecologic cancers at two tertiary centers between January 2018 and September 2022. RESULTS: The median age of the patients was 56 years (range, 35-79). Seven (35%), 1 (5%), 11 (55%), and 1 (5%) patients presented with cervical, vulvar, ovarian, and endometrial cancers, respectively. Sixteen (80%) patients received pembrolizumab and 4 (20%) received nivolumab at first treatment. Eight (40%) and 12 (60%) patients received pembrolizumab and nivolumab, respectively, at second treatment. At initial ICI treatment, 1 (5%) and 4 (20%) cases of a complete response (CR) and a partial response (PR) were observed, respectively, with a median progression-free survival (PFS) of 2.8 months (range, 1.4-49.6). Reasons for first ICI discontinuation were disease progression (n=16), severe adverse events (AEs) (n=2), and treatment withdrawal (n=2). During second ICI treatment, 1 (5%) patient achieved CR, 2 (10%) showed PR, and 5 (25%) experienced stable disease. The median PFS to second ICI was 1.8 months (range, 0.4-10.4). The median overall survival was 21.3 months (range, 10.1-52.7). Neither patient who discontinued ICI treatment due to AEs experienced AE relapse during second ICI treatment. CONCLUSION: These results suggest that responses to ICI rechallenge are not as intolerable as responses to previous ICI. Clinicians should carefully consider rechallenge with PD-1 inhibitors outside of clinical trials until there are sufficient data to routinely support this practice.

Identification of Lynch Syndrome in Patients with Endometrial Cancer Based on a Germline Next Generation Sequencing Multigene Panel Test.

We aimed to investigate the prevalence and relative contributions of LS and non-LS mutations in patients with endometrial cancer in Korea. We retrospectively reviewed the medical records of 204 patients diagnosed with endometrial cancer who underwent a germline next generation sequencing multigene panel test covering MLH1, MSH2, MSH6, PMS2, and EPCAM at three tertiary centers. Thirty patients (14.7%) with pathogenic mutations (12 MLH1; 6 MSH2; 10 MSH6; 2 PMS2) and 20 patients (9.8%) with 22 unclassified variants (8 MLH1; 8 MSH2; 2 MSH6; 3 PMS2; 1 EPCAM) were identified. After excluding four close relatives of a proband, the prevalence of LS was 13.0% (26/200). Patients with LS were more likely than those with sporadic cancer to be younger at diagnosis (48 vs. 53 years, p = 0.045) and meet the Amsterdam II criteria (66.7 vs. 3.5%, p < 0.001). Non-endometrioid histology was more prevalent in patients with MSH6 or PMS2 mutations (41.7%) than those with MLH1 or MSH2 mutations (5.6%, p = 0.026). In this pre-selected cohort of endometrial cancer patients who underwent next generation sequencing, the prevalence of LS was 13%, thus supporting the use of gene panel testing for endometrial cancer patients.

Long-term outcomes of photodynamic therapy for a positive resection margin after conization for cervical intraepithelial neoplasia grade 3.

BACKGROUND: Positive resection margins after conization or loop electrosurgical excision procedure (conization/LEEP) are associated with increased risks of recurrence or residual cervical intraepithelial neoplasia (CIN). Herein, we investigated the long-term outcomes of photodynamic therapy (PDT) for incomplete excision of CIN3. METHODS: We retrospectively reviewed the medical charts of 73 patients treated with PDT between 2000 and 2011. Patients who underwent conization/LEEP before PDT within 6 months were included. The primary outcomes were the complete response (CR) rate after 1 year and human papillomavirus (HPV) eradication rate at 6 months after PDT. RESULTS: A total of 34 patients with positive resection margins were finally enrolled. The median patient age was 33 years. Carcinoma in situ was diagnosed in 25 patients and CIN3 in 7 patients. The CR rate was 97.1% after 1 year. Except for one case of a persistent disease, there was no recurrence or newly developed disease during the median follow-up of 84 months (range, 12-224 months). The HPV eradication rate of PDT following conization/LEEP after 6 months was 96.9% (31/32). Photosensitivity was identified in five patients and cervical stenosis in one patient. CONCLUSIONS: In conclusion, PDT could be an effective therapeutic option for patients with a positive resection margin after conization/LEEP for CIN3. It could reduce the residual or recurrence rate of CIN lesions with tolerable adverse events.

The Association Between the Number of Retrieved Pelvic Lymph Nodes and Ipsilateral Lower Limb Lymphedema in Patients With Gynecologic Cancer.

PURPOSE: While the risk of lower limb lymphedema (LLE) after radical surgery for gynecologic malignancies is multifactorial, the limited assessment of lymph nodes (LNs), such as sentinel LN biopsy, has been incorporated into a standard procedure. We assessed the relationship between the number of LNs retrieved from the hemipelvis and the incidence of ipsilateral LLE (iLLE). METHODS: This retrospective study included 103 women with gynecologic cancer who had LNs removed with minimally invasive surgery between January 2014 and December 2018. For early detection of LLE, the patients were followed up by a lymphedema specialist who complied with the International Society of Lymphedema criteria. Potential risk factors for LLE were collected, and the risk factors were further investigated according to the number of LNs removed in a side-specific manner. RESULTS: LLE was diagnosed in 32 (31.1%) patients, and most of them were diagnosed with unilateral (n = 22) LLE rather than bilateral (n = 10). The number of pelvic LNs removed (p = 0.018), no lymphatic mapping (p = 0.034), and radiation (p = 0.020) were associated with the development of one or both LLEs. A side-specific analysis revealed that the incidence of iLLE increased significantly when four or more LNs were removed from the hemipelvis compared with three or fewer LNs (22.9% vs. 8.3%, p = 0.048). CONCLUSIONS: The number of pelvic LNs retrieved was associated with the incidence of LLE in patients with early gynecologic cancer. We identified the cutoff number per hemipelvis through side-specific analysis that could minimize the risk of iLLE. Further studies are needed to validate our results.

Transcatheter Arterial Embolization in the Management of Postpartum Hemorrhage due to Genital Tract Injury after Vaginal Delivery.

PURPOSE: To evaluate efficacy and safety of transcatheter arterial embolization (TAE) in managing postpartum hemorrhage (PPH) due to genital tract injury after vaginal delivery and to investigate factors associated with outcome of TAE. MATERIALS AND METHODS: A retrospective review of 43 women (mean age, 32.6 years) who underwent TAE to manage PPH secondary to genital tract injury after vaginal delivery was performed at a single institution between January 2007 and December 2018. Clinical data and outcomes were obtained. Patients were classified into clinical success (n = 39) and failure (n = 4) groups, and comparisons between the groups were performed. RESULTS: The clinical success rate of TAE for PPH due to genital tract injury was 90.7%. In the clinical failure group, transfusion volumes were higher (failure vs success: packed red blood cells, 14 pt ± 3.37 vs 6.26 pt ± 4.52, P = .003; platelets, 10.33 pt ± 4.04 vs 2.92 pt ± 6.15, P = .036); hemoglobin levels before the procedure were lower (failure vs success: 7.3 g/dL vs 10.7, P = .016). Periprocedural complications included pulmonary edema (25.6%), fever (23.3%), and pain (9.3%). Twenty-four patients were either followed for > 6 months or answered a telephone survey; 23 (95.8%) recovered regular menstruation, and pregnancy was confirmed in 11 (45.8%). Regarding fertility desires, 7 women attempted to conceive, 6 of whom (85.7%) became pregnant. CONCLUSIONS: TAE is an effective and safe method for managing PPH due to genital tract injury after vaginal delivery. Lower hemoglobin levels before the procedure and higher transfusion volumes were associated with clinical failure of TAE.

Non-surgical management and obstetric outcomes of heterotopic interstitial pregnancies.

Objective: To assess the effectiveness and safety of non-surgical management for six heterotopic interstitial pregnancies.Material and methods: We retrospectively analyzed the data of six women diagnosed with heterotopic interstitial pregnancies who underwent non-surgical treatment at the CHA Bundang Medical Center between January 2007 and December 2017. Three heterotopic interstitial pregnancies were treated with sono-guided potassium chloride (KCl) injections. Two cases were managed expectantly. One heterotopic quadruplet pregnancy with twin, left interstitial, and tubal pregnancy was treated by sono-guided KCl injection and laparoscopic left salpingectomy. Complications and outcomes were measured.Results: Three cases were treated with sono-guided KCl injection and the intrauterine pregnancy continued to term. Intrauterine pregnancies were vaginally delivered without complications. One case that was treated expectantly was delivered at full term, while the other case resulted in spontaneous abortion. Quadruplet heterotopic pregnancy was successfully managed with sono-guided KCl injection and laparoscopic salpingectomy. Intrauterine twin pregnancy was successfully delivered by elective cesarean section at 37 + 0 weeks of gestation with healthy babies. Conclusions: KCl injection under ultrasonographic guidance could be a safer and more effective treatment option than surgical treatment in hemodynamically stable patients with fetal cardiac activity in interstitial pregnancy. Expectant management could be an option for patients with no fetal cardiac activity.