Andreas Obermair

Description:Background: The standard treatment for endometrial cancer is hysterectomy with or without bilateral salpingo-oophorectomy; however, this may not be an optimal choice for women who have not completed childbearing or who are at a high risk of surgical complications. Conservative treatment with levonorgestrel intrauterine devices appear to be effective in patients with early-stage endometrial cancer; however, patients with mismatch repair-deficient (dMMR) tumors have a low likelihood of responding to levonorgestrel intrauterine devices. Objective: To assess the efficacy of dostarlimab, an active immune checkpoint inhibitor that targets the programmed cell death protein-1 receptor, in patients with early-stage dMMR endometrioid endometrial adenocarcinoma. Objective: Administration of 4 3-weekly cycles of 500 mg dostarlimab followed by a 3-week rest period and 3 6-weekly cycles of 1000 mg dostarlimab will be safe and efficacious in early-stage dMMR endometrial cancer patients. Methods: Non-randomized, open-label, pilot, multicenter phase2b study designed to evaluate the efficacy and safety of dostarlimab in 10 women aged ≥18 years with a clinically confirmed diagnosis of early-stage and dMMR endometrioid endometrial adenocarcinoma. Eligible patients must have histologically proven stage I, International Federation of Gynecology and Obstetrics grade 1 or 2 dMMR endometrioid endometrial adenocarcinoma and desire for fertility preservation. Exclusions include, but are not limited to, patients with other high-risk endometrial cancer cell types, a poor medical risk due to uncontrolled medical conditions, or those who experienced grade 3 or higher immune-related adverse events from prior immunotherapy. The primary endpoint is the number of participants achieving investigator-assessed pathological complete response within 6 months of treatment. Methods: Ten (10) women ≥18 years of age will be enrolled. Accruals are expected to be completed by 2027, with the presentation of results by 2029. Background: NCT06278857.

Description:In the original published version of this article, the following errors were introduced during the copyediting process by the Suppliers. The text originally published “This study (feaSibility sAfeTy Efficacy dostarLimab earLy-stage defIcient endomeTrial cancEr) aims to determine the anti-tumor activity and safety of dostarlimab in patients with dMMR earlystage endometrial cancer.” Has been corrected to “The aim of the SATELLITE study (feaSibility sAfeTy Efficacy dostarLimab earLy-stage defIcient endomeTrial cancEr) is to determine the anti-tumor activity and safety of dostarlimab in patients with dMMR earlystage endometrial cancer.” The text originally published “Dostarlimab at fixed doses of 500 mg administered intravenously every 3 weeks and 1000 mg administered every 6 weeks reflected the regimen used in standard oncology clinical practice.” Has been corrected to “The dosing of dostarlimab at fixed doses of 500 mg administered intravenously every 3 weeks and 1000 mg administered every 6 weeks reflects the regimen in standard oncology clinical practice.” The text originally published “Eligible participants with histologically or cytologically proven stage I, International Federation of Gynecology and Obstetrics (FIGO) grade 1 or 2, and dMMR endometrial adenocarcinoma will receive 7 cycles of intravenous infusion of dostarlimab as per protocol, comprising 4 cycles of 500 mg 3-weekly, a rest period of 3 weeks, followed by 3 cycles of 1000 mg 6-weekly, until the occurrence of any of the following: unacceptable toxicity or other conditions preventing further administration, progressive disease, termination of the trial, or clinicians’ or participants’ decision to withdraw from treatment (Fig.). Participants who withdrew from treatment owing to tumor progression at the interval evaluation will be referred to the gynecological oncology team and treated according to standard clinical practice.” Has been corrected to “Eligible participants with histologically or cytologically proven stage I, International Federation of Gynecology and Obstetrics (FIGO) grade 1 or 2, dMMR endometrial adenocarcinoma will receive 7 cycles of intravenous infusion of dostarlimab as per protocol, comprising 4 cycles of 500 mg 3-weekly, a rest period of 3 weeks, followed by 3 cycles of 1000 mg 6-weekly, until the occurrence of any of the following: unacceptable toxicity or other conditions preventing further administration, progressive disease, termination of the trial, or clinicians’ or participants’ decision to withdraw from treatment (Fig.). Participants who withdraw from treatment due to tumour progression at interval evaluation will be referred to the gynaecological oncology team and treated according to standard clinical practice.” The text originally published “This study was approved by the Metro North Health Human Research Ethics Committee (HREC/2023/MNHA/104200), and conducted at 3 sites in Australia.” Has been corrected to “This study was approved by the Metro North Health Human Research Ethics Committee (HREC/2023/MNHA/104200) and will take place at 3 sites in Australia.” The text originally published “Clinical investigations will be conducted according to local vendor requests and reporting protocols.” Has been corrected to “Clinical investigations will be conducted following local/vendor request and reporting protocols.” The text originally published “Potentially eligible patients had histologically or cytologically proven evidence of clinical stage I FIGO grade 1 or 2 endometrial cancer with dMMR, defined as the absence of at least 1 MMR protein (MLH1, PMS2, MSH2, or MSH6).” Has been corrected to “Potentially eligible patients have histologically or cytologically proven evidence of clinical stage I FIGO grade 1 or 2 endometrial cancer with dMMR, defined as the absence of at least 1 MMR protein (MLH1, PMS2, MSH2, or MSH6).” The text originally published “These investigations will include the following: medical, surgical, and gynecologic history; concurrent medical conditions; concomitant medications; physical examination; vital signs; cardiology evaluation, including echocardiography and 12-lead electrocardiogram; laboratory/diagnostic tests, including pregnancy test (serum human chorionic gonadotropin for females of childbearing potential only), full blood count, follicle-stimulating hormone (for post-menopausal women only), glycated hemoglobulin, CA125, full hematology and chemistry panel, coagulation panel, and full hormone and serology panel; urine analysis; ECOG functional status; adverse event assessment.” Has been corrected to “These investigations will include the following: medical, surgical, and gynecologic history; concurrent medical conditions; concomitant medications; physical examination; vital signs; cardiology evaluation, including echocardiography and 12-lead electrocardiogram; laboratory/diagnostic tests, including pregnancy test (serum human chorionic gonadotropin for females of childbearing potential only), full blood count, follicle-stimulating hormone (for post-menopausal women only), glycated hemoglobulin, CA125, full hematology and chemistry panel, coagulation panel, and full hormone and serology panel; urine analysis; ECOG functional status; adverse event assessment; and serum and plasma collection for exploratory outcomes/biobanking.” The text originally published “Exploratory objectives included assessing the feasibility of the study, qualitative evaluation of participation to inform future clinical research, changes in clinical and laboratory parameters after treatment with dostarlimab, fertility outcomes to inform fertility preservation approaches to treatment and utilization of biobanked tissue and blood samples of participants treated with dostarlimab to investigate biomarker relationships.” Has been corrected to “Exploratory objectives include assessing the feasibility of the study, qualitative evaluation of participation to inform future clinical research, changes in clinical and laboratory parameters after treatment with dostarlimab, fertility outcomes to inform fertility preservation approaches to treatment and utilization of biobanked tissue and blood samples of participants treated with dostarlimab to investigate biomarker relationships.” The text originally published “As a single-arm, open-label trial, it required no randomization or blind/unblinding procedures.” Has been corrected to “As a single-arm, open-label trial, it requires no randomization or blinding/unblinding procedures.” The text originally published “There will be no formal interim analysis; however, the pathological complete response event rate will be monitored to enable the implementation of the predefined early stopping rules, whereby after the enrollment and treatment of 5 participants, if fewer than 2 participants have achieved investigator-assessed pathological complete response or after the enrollment and treatment of 7 participants if fewer than 3 participants have achieved pathological complete response, the trial will be stopped.” Has been corrected to “There will be no formal interim analysis; however, the pathological complete response event rate will be monitored to enable the implementation of the predefined early stopping rules, whereby after the enrollment and treatment of 5 participants, if fewer than 2 participants have achieved investigator-assessed pathological complete response or after the enrollment and treatment of 7 participants if fewer than 3 participants have achieved pathological complete response, consideration will be given to stopping the trial.” The text originally published “The disposition listing created for each participant included the date of informed consent, date and time of administration of the first dose of dostarlimab, study completion or discontinuation, reasons for discontinuation, and inclusion in each analysis set.” Has been corrected to “A disposition listing created for each participant will include date of informed consent, date and time of administration of first dose of dostarlimab, study completion or discontinuation, the reason for discontinuation, and whether to include in each analysis set.” The text originally published “Safety endpoints included the incidence of treatment-emergent adverse events, immune-related adverse events of interest, and serious adverse toxicities graded 3-5 as to the National Cancer Institute Common Terminology Criteria for adverse events.” Has been corrected to “Safety endpoints included the incidence of treatment-emergent adverse events, immune-related adverse events of interest, and serious adverse toxicities graded 3-5 as per the National Cancer Institute Common Terminology Criteria for adverse events.” These errors bear no reflection on the article or its authors. The publisher apologizes to the authors and the readers for this unfortunate error.

Description:Objective: To evaluate patterns of care, post-operative adverse events, and recurrence rates in patients with vulval squamous cell carcinoma, undergoing sentinel node biopsy or inguino-femoral lymph node dissection. Methods: A retrospective analysis was conducted on a cohort of 124 patients with vulval squamous cell carcinoma between 2016 and 2020 who met the study eligibility criteria. We compared the proportion of patients who underwent sentinel node biopsy versus inguino-femoral lymph node dissection, along with their rates of post-operative adverse events, recurrences, and associated socioeconomic factors. Results: Of the 124 patients, 58 (46.8%) underwent inguino-femoral lymph node dissection, and 66 (53.2%) underwent sentinel node biopsy. The utilization of sentinel node biopsy increased over the study period from 34.5% to 57.1%. Overall, 67 of 121 patients (55.4%) experienced at least one post-operative adverse event. The incidence of adverse events was significantly higher in the inguino-femoral lymph node dissection group compared to the sentinel node biopsy group (87.9% vs 24.4%, p < .0001). Lymphoedema (n = 26, 44.8% vs n = 4, 6.4%), seroma (n = 30, 24.6% vs n = 6, 9.5%), and infections (n = 23, 19.0% vs n = 8, 12.7%) were more frequent in the inguino-femoral lymph node dissection group than in the sentinel node biopsy group. Recurrence rates and time to recurrence were comparable between groups. Socioeconomic factors had no impact on patient outcomes. Conclusions: Only approximately half of the patients requiring a groin lymph node assessment had a sentinel node biopsy. Morbidity associated with vulval cancer treatment remains high. Further research is warranted to reduce the treatment burden without compromising survival outcomes.

Description:Objective: Intra-operative adverse events contribute to postoperative morbidity and mortality. Although these events vary in their impact on patient recovery, no classification system has been available that accounts for this variation. We propose a scoring system that groups intra-operative adverse events in gynecological cancer surgery based on their impact on patient outcomes. Methods: We conducted an investigator-led, multistage development of the Classification of intra-operative Adverse Surgical Events (CiASE) grading system. CiASE grades range from 0 (absence of intra-operative adverse events) to 4 (death) and were assigned by the investigators to 17 surgical case vignettes. Validation of the CiASE grading system was performed by 25 surgeons from 3 countries (Australia, New Zealand, and Ireland) who were blinded to the benchmark grade for each vignette. After validation, real-world analysis of CiASE was performed via applying grades to real cases reported to our institution for review between 2022 and 2023. Results: The benchmark CiASE grade assigned to the vignettes matched the surgeons' grading in 16.2 out of 17 cases on average, yielding an accuracy of 95.2%. Sensitivity for each individual grade ranged from 88% to 100%, and specificity ranged from 97.8% to 100%. Inter-rater agreement among the 25 surgeons was almost perfect, with a chance-adjusted weighted Krippendorff's Alpha score of 0.95 (95% CI 0.88 to 0.99). Among 179 real cases of intra-operative adverse events assessed, we classified 86 cases as CiASE grade 0 (48%; absence of intra-operative adverse events), 52 cases as grade 1 (29%; minimal impact on patient well-being), 24 cases as grade 2 (13%; moderate impact), 17 cases as grade 3 (10%; severe impact), and no cases as grade 4 (0%; death). Conclusions: CiASE is a grading system for intra-operative adverse events that accounts for their impact on patient outcomes in gynecological cancer surgery. Future research is required to assess its utility for quality assurance, education, teaching, and feedback.

Description:Objective: Imaging for staging ovarian cancer is important to determine the extent of disease. The primary objective of this study was to compare gated 18F-fluorodeoxyglucose positron emission tomography coupled with computed tomography (FDG PET/CT) and standard CT scan with intravenous contrast to diagnose thoracic involvement in patients with advanced ovarian cancer prior to treatment. The secondary objective was to estimate changes in the International Federation of Gynecology and Obstetrics (FIGO) stage and clinical management resulting from gated PET/CT. Methods: The IMAGE trial is a non-randomized phase II clinical trial comparing standard CT scanning with gated PET/CT in diagnosing thoracic involvement in a non-selected group of patients with suspected ovarian cancer on a contrast CT scan. Three sets of PET images were obtained comprising an ungated 2 min whole body image, a static 7.5 min image of the upper abdomen and thorax, and a gated end-expiratory image over the upper abdomen and thorax. Images were evaluated for specificity, sensitivity, diagnostic accuracy, and the proportion of patients with changes in FIGO stage and subsequent clinical management was compared between imaging techniques. Results: A total of 84 patients were enrolled based on a standard CT scan, 67 of whom were eligible for gated PET/CT scans. Diagnostic accuracy with gated PET/CT was more than 80% for lesions in lung, liver, extra-abdominal sites, and pleura, but less than 50% for extra-abdominal lymph nodes. Compared with CT scan at baseline, 46% of patients who had 7.5 min gated PET/CT had disease upstaged from stage III to IV, and 8% had disease downstaged from stage IV to III. However, this led to a change of management in only 5% of patients. Conclusions: Gated PET/CT enables upstaging; however, in our institution it altered clinical management only in a minority of patients.