Alon D. Altman

Mode of Minimally Invasive Surgery Associated with Venous Thromboembolism Incidence in Gynecologic Cancer Patients

Postoperative venous thromboembolism (VTE) after minimally invasive surgery (MIS) for gynecologic malignancy is uncommon. Our objective was to characterize the rates and identify risk factors of postoperative VTE. A retrospective cohort study of patients undergoing MIS for gynecologic malignancy at three Canadian institutions from 2014 to 2020 was performed. The primary outcome was incidence of VTE within 90 days post-operatively. Descriptive statistics were used for clinicopathologic factors, and univariate analysis compared differences between groups. Rate and 95% confidence interval for VTE per 1000 surgeries were calculated. A total of 1786 patients met inclusion criteria, 85.3% uterine, 11.5% cervical, and 2.3% had ovarian cancer. Modes of surgery included robotic (49.4%), laparoscopic (20.7%), or combined laparoscopic/vaginal (29.9%). There were 15 VTE events at 90 days post-operatively (0.84%). Rates of VTE were lowest in patients who underwent robotic surgery, followed by combined laparoscopic/vaginal, and highest in a laparoscopic approach (p = 0.047). Pelvic lymphadenectomy (p = 0.038) and adjuvant chemotherapy (p = 0.022) were the only significant factors associated with risk of VTE. The incidence of VTE after MIS for gynecologic malignancy is low. Robotic surgery was associated with a lower incidence, although event rates are low, and further research is warranted.

Ovarian Cancer in the Older Manitoban Population—Treatment Tolerance and Cancer-Related Outcomes: A Manitoba Ovarian Cancer Outcomes (MOCO) Group Study

Background: In Canada, individuals with gynecologic reproductive organs (ovaries, fallopian tubes, uterus) over the age of 70 comprise a large proportion of epithelial ovarian cancer patients. These patients often have co-morbidities, polypharmacy, or decreased functional status that may impact treatment initiation and tolerance. Despite this, there is limited evidence to guide treatment for older patients diagnosed with ovarian epithelial carcinoma. Methods: This is a retrospective study with data from Manitoba, Canada. The data were obtained from the Manitoba Ovarian Cancer Database, the Manitoba Cancer Registry, and electronic health records. All individuals with epithelial ovarian, fallopian tube, or peritoneal cancer diagnosed between 2009 and 2018 were identified. Patients aged > 70 at the time of diagnosis were included in the study cohort. Results: Four hundred and forty individuals were included. The majority had advanced stage disease (56%). Moreover, 59% of patients received no chemotherapy. Of the patients who received chemotherapy, 20% received <2 cycles and 21% required a dose reduction due to toxicity. Univariable and multivariable analysis identified advanced stage (p < 0.001), treatment modality (p < 0.001), and advanced age at diagnosis (p < 0.001) with poorer overall survival. Conclusions: Our study demonstrated a high rate of chemotherapy dose reduction and discontinuation in the elderly epithelial ovarian cancer population. Further research is needed to identify risk factors for treatment discontinuation and intolerance in this population.

Olaparib as treatment for platinum‐sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency: Phase 2 LIGHT study final overall survival analysis

AbstractBackgroundLIGHT (oLaparib In HRD‐Grouped Tumor types; NCT02983799) prospectively evaluated olaparib treatment in patients with platinum‐sensitive relapsed ovarian cancer (PSROC) assigned to cohorts by known BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD‐positive non‐BRCAm, and HRD‐negative. At the primary analysis, olaparib treatment demonstrated activity across all cohorts, with greatest efficacy in terms of objective response rate and progression‐free survival observed in the g/sBRCAm cohorts. The authors report final overall survival (OS).MethodsIn this phase 2, open‐label, noncomparative study, patients with PSROC and one or more prior line of platinum‐based chemotherapy were assigned to cohorts by BRCAm and HRD status. OS was a secondary end point. Tumors were analyzed using Myriad BRACAnalysis CDx and MyChoice CDx assays; HRD‐positive tumors were defined using a genomic instability score of ≥42.ResultsOf 272 enrolled patients, 271 received olaparib and 270 met the inclusion criteria for the efficacy analysis. At data cutoff, 18‐month OS rates in the gBRCAm, sBRCAm, HRD‐positive non‐BRCAm, and HRD‐negative cohorts were 86.4%, 88.0%, 78.6%, and 59.6%, respectively. No new safety signals were observed. In a post hoc analysis, patients on treatment for >18 months were most frequently present in g/sBRCAm cohorts (31.0%).ConclusionsOlaparib treatment continued to demonstrate benefit across all cohorts. Consistent with the primary analysis, the highest OS rates were observed in the BRCAm cohorts, regardless of g/sBRCAm. In patients without a BRCAm, a higher OS rate was observed in the HRD‐positive non‐BRCAm than the HRD‐negative cohorts. These results highlight the importance of biomarker testing in this treatment setting.

Exploring the role of a multidisciplinary hereditary gynecologic oncology clinic in epithelial ovarian cancer risk‐reducing surgical decision‐making practices: A mixed‐methods study

AbstractIndividuals that have gynecologic reproductive organs with pathogenic variants in BRCA1 or BRCA2 (“BRCA‐positive”) have an increased risk of developing high‐grade serous ovarian cancer (HGSOC). The majority of HGSOC develops in the fallopian tubes and later spreads to the ovaries and peritoneal cavity. Therefore, risk‐reducing salpingo‐oophorectomy (RRSO) is recommended for those who are BRCA‐positive to preventatively remove their ovaries and fallopian tubes. The Hereditary Gynecology Clinic (HGC) is a provincial program in Winnipeg, Canada, that specifically targets care to the unique needs of such individuals through an interdisciplinary team of gynecological oncologists, menopause specialists, and registered nurses. A mixed‐methods study design was used to explore the decision‐making processes of these BRCA‐positive individuals who have been recommended (or who completed) RRSO and experiences with healthcare providers at the HGC influenced this decision. Individuals who are BRCA‐positive without a previous diagnosis of HGSOC and who had previously received genetic counselling were recruited from the HGC and the provincial cancer genetics program (Shared Health Program of Genetics & Metabolism). Forty‐three people completed a survey and 15 participated in an in‐depth interview about their experiences and decisions surrounding RRSO. Surveys were analyzed to compare scores on validated scales related to decision‐making and cancer‐related worry. Qualitative interviews were transcribed, coded, and analyzed using interpretive description. Participants described the complex decisions faced by those who are BRCA‐positive, which are intertwined with life experiences and circumstances including age, marital status, and family disease history. Participants interpreted their HGSOC risk through a personalized “lens” of contextual factors that impacted perceptions about the practical and emotional implications of RRSO and the need for surgery. Mean scores on validated scales evaluating the HGC's impact on decisional outcomes and preparedness for decision‐making about RRSO were not significant, indicating that the HGC played a supportive role, rather than helping with decision‐making itself. Therefore, we present a novel framework that consolidates the various influences on decision‐making and connects them to the psychological and practical implications of RRSO in the context of the HGC. Strategies for improving support, decisional outcomes, and the overall experiences of individuals who are BRCA‐positive attending the HGC are also described.

Response to Multi-Line Chemotherapy in Non-Serous Epithelial Ovarian Cancer

To describe the response rate to chemotherapy, rates of recurrence, and overall survival in patients with non-serous epithelial ovarian cancers. This retrospective cohort study used the Manitoba Cancer Registry to identify all women with non-serous epithelial ovarian, fallopian, or peritoneal cancer treated between 1995 and 2010. Chart review entailed extracting information regarding therapy and outcomes. All patients with recurrence were identified and response to chemotherapy was assessed. We identified 392 patients with non-serous ovarian cancers, 192 of whom received chemotherapy in the first-line setting. Optimal debulking resulted in improvements in rates of recurrence and overall survival (P mucinous > clear cell > endometrioid) and in the third-line setting, 33.3%-75.0% of patients (other > mucinous > clear cell > endometrioid) received >6 lines of chemotherapy. Twenty-three percent of patients experienced a recurrence within 2 years of first-line therapy. Two-year survival was 79.4% after first-line treatment, 27.6% after second-line treatment, and 19.5% after third-line treatment. Patients with clear cell ovarian cancer had chemotherapy continuation rates similar to those of previously reported studies. This is one of the first studies reporting response rates for mucinous and endometrioid subtypes. Recurrent disease responds to treatment with second- and third-line therapy, emphasizing the importance of offering patients subsequent lines of chemotherapy for disease management. Further studies are needed to determine the optimal regimen.

Referral, Genetic Counselling, and BRCA Testing in the Manitoba High-Grade Serous Ovarian Cancer Population, 2004–2019

(1) Background: The primary objective of this study was to examine the rate of genetic referral, BRCA testing, and BRCA positivity amongst all patients with high-grade serous ovarian cancers (HGSOC) from 2004–2019. The secondary objective was to analyze secondary factors that may affect the rates of referral and testing. (2) Methods: This population-based cohort study included all women diagnosed with HGSOC using the Manitoba Cancer Registry, CervixCheck registry, Medical Claims database at Manitoba Health, the Hospital Discharge abstract, the Population Registry, and Winnipeg Regional Health Authority genetics data. Data were examined for three different time cohorts (2004–2013, 2014–2016; 2017–2019) correlating to practice pattern changes. (3) Results: A total of 944 patients were diagnosed with HGSOC. The rate of genetic referrals changed over the three timeframes (20.0% → 56.7% → 36.6%) and rate of genetic testing increased over the entire timeframe. Factors found to increase rates of referral and testing included age, histology, history of oral contraceptive use, and family history of ovarian cancer. Prior health care utilization indicators did not affect genetic referral or testing. (4) Conclusion: The rate of genetic referral (2004–2016) and BRCA1/2 testing (2004–2019) for patients with a diagnosis of HGSOC increased over time. A minority of patients received a consultation for genetics counselling, and even fewer received testing for a BRCA1/2. Without a genetic result, it is difficult for clinicians to inform treatment decisions. Additional efforts are needed to increase genetics consultation and testing for Manitoban patients with HGSOC. Effects of routine tumour testing on rates of genetic referral will have to be examined in future studies.

Perioperative Incidence of Venous Thromboembolism in Patients With Ovarian Cancer Using Four Different Data Collection Methods: A Manitoba Ovarian Cancer Outcomes (MOCO) Group Study

To evaluate the incidence of venous thromboembolism (VTE) in 90-day pre-operative period and at 30 and 90 days post surgery in patients who underwent debulking for ovarian cancer, analyze the impact of extended prophylaxis that was initiated in 2012, and examine the influence of data collection technique on reported rates of VTE. This retrospective database and records study examined rates of VTE in epithelial ovarian cancer patients in Manitoba, Canada between 2004 and 2016. Cases of VTE were identified using ICD codes, drug prescriptions, and records reviews; 4 different data collection methods were used. Analysis was performed with analysis of variance, Kruskal-Wallis and χ Data collection identified 823 debulking surgeries, with a final cohort of 779 patients; data were analyzed before and after extended prophylaxis intervention. Overall rates of VTE varied by collection method and were 1.82%-5.47%, 0.36%-3.16%, 0.85%-1.46%, and 1.46%-2.79%, respectively. During this timeframe, we noted a significant increase in the use of neoadjuvant chemotherapy (P = 0.010) and stage migration to stage 3 (P < 0.001). We report the rates of VTE utilizing 4 different data collection methods. We found a low overall rate, with some trends requiring further investigation. This study highlights the importance of data collection method on the reported rates of VTE in research.

A Pan-Canadian Consensus Statement on First-Line PARP Inhibitor Maintenance for Advanced, High-Grade Serous and Endometrioid Tubal, Ovarian, and Primary Peritoneal Cancers

The majority of patients with advanced, high-grade epithelial-tubo ovarian cancer (EOC) respond well to initial treatment with platinum-based chemotherapy; however, up to 80% of patients will experience a recurrence. Poly(ADP-ribose) Polymerase (PARP) inhibitors have been established as a standard of care maintenance therapy to prolong remission and prevent relapse following a response to first-line platinum-chemotherapy. Olaparib and niraparib are the PARP inhibitors currently approved for use in the first-line maintenance setting in Canada. Selection of maintenance therapy requires consideration of patient and tumour factors, presence of germline and somatic mutations, expected drug toxicity profile, and treatment access. This paper discusses the current clinical evidence for first-line PARP inhibitor maintenance therapy in patients with advanced, high-grade EOC and presents consensus statements and a treatment algorithm to aid Canadian oncologists on the selection and use of PARP inhibitors within the Canadian EOC treatment landscape.