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The proceedings contain 358 papers. The topics discussed include: role of early prophylactic aspirin on Covid-19 outcome in antenatal patients - an audit of a hospital in India;partial intestinal obstruction complicating pregnancy: diagnostic dilemma and management;a case report of uterine rupture recognized during cesarean section at the site of a previous hysteroscopy-related perforation;menstrual characteristics and its related morbidities among adolescent girls living in North Borneo, Malaysia: a questionnaire-based study;the volume of posterior cervical varicose correlates with intraoperative blood loss in placenta previa;implications of large fibroids in pregnancy: a multidisciplinary approach;unexpected ovarian malignancy in postmenopausal women following laparoscopic surgery for adnexal masses - a review of 5 years;post radiotherapy outcome on cervical cancer stage IIIB patients with and without paraaortic lymph nodes enlargement;and evaluation of the relationship between thrombocytosis and clinico-pathological factors of patients with epithelial ovarian cancer.
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Objectives: Immune checkpoint blockade (ICB) has demonstrated efficacy in a small fraction of patients with platinum-resistant ovarian cancer (PROC), some with durable responses. The receptor tyrosine kinase AXL and its sole ligand, GAS6, are possible mediators of T cell exclusion and an attractive target due to the expected synergy between AXL inhibition and immune targeting agents. The recommended phase II dose (RP2D), safety, and efficacy of the combination of AXL inhibition via AVB-S6-500 with durvalumab (MEDI4736) were evaluated in patients with PROC. Methods: In this open-label Phase Ib open-label study, patients with PROC received AVB-S6-500 and durvalumab therapy in escalating dosing regimens guided by a Bayesian optimal interval (BOIN) design: durvalumab (1500 mg Q4W) and AVB-S6-500 (10mg/kg Q2W, 15mg/kg Q2W, 20mg/kg Q2W) with durvalumab infused prior to AVB-S6-500. The response was evaluated using modified RECIST v1.1. Pharmacokinetic/pharmacodynamic (PK/PD) studies were collected, and PD-L1 status and tumor/tumor microenvironment AXL and GAS6 staining pre and on-treatment were assessed. Results: Eleven patients with epithelial ovarian cancer (six clear cells [55%], four high-grade serous [36%], one endometrioid histology [1%]) received treatment per protocol. The median number of prior lines of therapy was 3 (range: 1-5);73% (8/11) of patients had received prior bevacizumab. There were no DLTs noted over the 6-week period and no grade ≥3 adverse events attributed to study drugs. Five patients experienced an immune-related AE, most commonly liver enzyme elevations (36%). Infusion reaction with AVB-S6- 500 was noted in the first two subjects, prompting the institution of a premedication regimen, after which only one of the nine additional patients experienced an infusion reaction. Dose delays greater than one week occurred in six (55%) patients;three patients experienced delays for cancer-related complications (small bowel obstruction, pneumonia, severe fatigue), while three patients experienced delays for non-medical causes (COVID/travel, weather). Patients received therapy for a median of two cycles (range: 1-6), and there were no responses noted across all dosing levels. One patient had stable disease, with a duration of response of three months. Only two patients had strong (2+) AXLstaining on pretreatment biopsy, both with high-grade serous histology. The majority of serum AXL levels were within previously demonstrated ranges (range: 5.6-112ng/mL), though two patients had comparatively high levels (102, 112ng/mL). PK/PD analysis revealed expected AVB-S6-500 levels at initial postdose (C1D1), but low levels at trough (C2D1 predose) when compared to prior AVB-S6-500 data [1]. Conclusions: The combination of AVB-S6-500 and durvalumab was tolerable in this PROC patient population at all dosing levels tested. Exploratory studies to correlate lack of response to AXL-GAS6 pathway alterations, tumor microenvironment, and clinical characteristics, such as prior treatment, dosing delays, burden of disease, and ascites, are ongoing.
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Objectives: In light of the COVID-19 pandemic, the Society of Gynecologic Oncology (SGO), National Cancer Institute, and Food and Drug Administration published clinical practice statements encouraging the use of telemedicine in clinical trials, which had previously been prohibited. Our study aimed to assess the feasibility and safety of telehealth utilization in clinical trials for gynecologic malignancies. Methods: A retrospective cohort study was performed. Patients who were enrolled in a gynecologic oncology clinical trial at the University of Pennsylvania Health System from March 16, 2020, to August 30, 2020, were included. Receipt of care during the telehealth period (March 16, 2020, to August 30, 2020) was compared to the pre-telehealth period (September 30, 2019, to March 15, 2020). Pairwise comparisons of clinical trial outcomes were performed between the two time periods, using paired t-test, Wilcoxon signed-rank test, simple linear regression, Chi-square, and ANOVA. Results: Thirty-one patients met the inclusion criteria. The mean age was 63.7 years (SD 10.3);84% were non-Hispanic White. The median distance from home zip code to study center was 25.2 miles (IQR: 16-46, range: 1.9-170). Most patients had high-grade serous ovarian carcinoma (84%) and had the disease at an advanced stage (Stage III 48%, Stage IV 38.7%). Trial drugs included 22.6% (n=7) intravenous only, 29% (n=9) oral only, and 48.4% (n=15) combination oral/intravenous therapies. The median duration of enrollment was similar between pre-telehealth (5.2 months, IQR: 3.2-5.6) and telehealth periods (5.6 months, IQR: 3.8-5.6), (p=0.682). During the TELEHEALTH period, significantly more virtual provider visits (p <0.001) and remote laboratory testing (p=0.015) occurred, with similar rates of remote imaging (p=0.551). Delayed provider visits (p = 0.965), laboratory testing (p = 0.989) and imaging (p = 0.999) occurred infrequently in both timeframes. The number of patient touchpoints (portal messages and phone calls) per month did not increase (p = 0.147). Patients who lived farther from the study center were more likely to use remote imaging (p = 0.013);however, the distance was not associated with the use of virtual provider visits (p = 0.309) or remote laboratory testing (p = 0.821). Number of dose reductions (p = 0.112) and toxicity-related treatment delays (p = 0.888) were similar. Increased need for extra imaging was noted in the telehealth period (p=0.007) and was not associated with disease progression (p=0.614). Extra provider visits, emergency department visits, and hospital admissions were infrequent and similar in both timeframes (Table 1). The total number of deviations was increased (p=0.010);however, when adjusted for minor deviations documenting telehealth use or deferment of research-related laboratory testing given the pandemic precautions, there was no difference between timeframes (p = 0.468). The total number of adverse events and severe adverse events did not increase in the telehealth period (p=0.494 and p=0.601, respectively). Conclusions: Utilizing telehealth in clinical trials for gynecologic oncology patients did not increase clinical workload or adverse patient outcomes. Documentation of telehealth use and pause of research-related laboratory collections resulted in a higher number of protocol deviations during the telehealth period. Telehealth should be incorporated into future clinical trials as it appears safe and feasible and may facilitate access for remote, rural, and under-served populations.
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Background: Carboplatin, gemcitabine +/-bevacizumab is a preferred regimen for recurrent, platinumsensitive ovarian cancer (PSOC). A phase III trial established that the regimen of carboplatin on Day 1 (D1) and gemcitabine on D1 and Day 8 (D8) was associated with acceptable toxicity and improved progression free survival (PFS) compared to carboplatin alone. Treatment with gemcitabine on D8 incurs more exposure to cytotoxic therapy and increased burden on patients and the healthcare system, especially during the COVID-19 pandemic. However, it is unknown whether D1/D8 gemcitabine imparts an improvement in efficacy compared to D1 alone. Our objective was to compare efficacy and toxicity of carboplatin and gemcitabine D1/D8 (CG-D1/8) with a modified D1 regimen (CG-D1). Methods: A retrospective single-institution cohort study was performed in women with recurrent PSOC treated with carboplatin, gemcitabine +/-bevacizumab from 2009-2020. Data was analyzed by intention to treat comparing women who received CG-D1/8 vs CG-D1. Data was also analyzed by 3 groups: CG-D1/8 vs CG-D1/8 but dropped D8 vs CG-D1. The primary endpoint was response rate (RR), defined as complete or partial response at 6 cycles or maximum cycles if <6. Secondary outcomes included PFS, overall survival (OS), toxicity, Neulasta use and dose reduction. Results: Of 200 patients, 26% completed CGD1/ D8, 21.5% started CG-D1/D8 but dropped D8, and 52.5% received CG-D1. There were no significant differences in age, race, or ECOG between cohorts. Among CG-D1/D8, 45.3% dropped D8 primarily due to neutropenia (51.2%) or thrombocytopenia (30.2%). The RR at 6 cycles was 68.7% for CG-D1/8 completed, 70.7% for CG-D1/8 dropped D8, and 69.3% for CG-D1 (p=0.97). The median PFS was 13.1, 12.1 and 12.4 months for CG-D1/8 completed, CG-D1/8 dropped D8, and CG-D1, respectively (p=0.29). Similarly, median OS was 28.2, 33.5 and 34.3 months for the above groups respectively (p=0.42). While there was no difference in concurrent bevacizumab use for CG-D1/8 and CG-D1 (34.7% vs 29.5%, p=0.43), among the CG-D1/8 patients, a significantly higher proportion of patients who dropped D8 received bevacizumab (51.2% vs 21.2%, p=0.006). Table 1 lists secondary outcomes. Conclusions: There was no significant difference in RR, PFS or OS among women with PSOC receiving CG-D1/8 vs CG-D1, regardless of whether D8 was dropped. CG-D1/8 was associated with significantly greater hematologic toxicity. These findings suggest a modified D1 regimen may be a suitable alternative to standard CG-D1/8 treatment and warrant prospective validation.
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Introduction/Background MIRRORS (Minimally Invasive Robotic surgery, Role in optimal debulking Ovarian cancer, Recovery & Survival) is the largest prospective cohort study of robotic interval debulking surgery (IDS) in women with advanced-stage epithelial ovarian cancer (EOC) to date. MIRRORS has investigated the feasibility of obtaining consent from women, the acceptability and success of robotic IDS and its impact on short-term surgical outcomes and quality of life. Methodology Eligibility Women with FIGO IIIc-IVb EOC undergoing neoadjuvant chemotherapy and suitable for IDS. Exclusions: pelvic mass >8cm, extensive HPB and/or extensive bowel involvement. Surgery commenced with an initial laparoscopic assessment, for all women recruited, followed by a decision to proceed immediately to robotic or open IDS. Result(s) 23/24 eligible women recruited. Following initial diagnostic laparoscopy, 20 women proceeded directly to robotic IDS, 3 women received open IDS. All patients were debulked with maximal surgical effort to R<1, 39% to R=0. No robotic cases were converted to open. Median EBL for robotic IDS: 50ml, open: 2026ml, median operating time 05:58 robotic vs 05:38 open, length of stay (LOS) 1.5 days robotic vs 6 days open. Bowel resection with stapled anastomosis 15% (3/20), diaphragmatic stripping 60% (12/20), fullthickness diaphragmatic resection 5% (1/20), pelvic peritoneal stripping 70% (14/20). Conclusion MIRRORS has shown significantly enhanced recovery with short LOS, reduced blood loss and reduced HDU/ITU demands, enabling faster re-commencement of chemotherapy in women with FIGO IIIc-IVb EOC. This proved to be greatly beneficial during the COVID-19 pandemic. In experienced hands robotic IDS proved feasible in cases with a pelvic mass up to 8cm. Robotic surgery is not suitable for peritoneal disease covering the anterior abdominal wall close to port sites but does facilitate pelvic and diaphragmatic stripping and arguably provides better visualisation of these peritoneal surfaces in women with high BMI. The planned multicentre MIRRORS-RCT will assess whether robotic IDS offers improved quality of life and recovery with non-inferior progression-free and overall survival. We present the evolution of our surgical technique with illustrative surgical videos and qualitative patient feedback, supported by the objective surgical outcomes for this trial.
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The coronavirus disease (COVID) pandemic has impacted the health sector in massive proportions. Perhaps the worst affected aspect is that of oncological care. Cancer patients continue to suffer silently due to nonavailability of consultations and shortage of operating rooms. We need to brace ourselves for the impact of this backlog of nearly 18 months of neglected care of such patients.