Laparoscopic predictability of minimally invasive interval debulking in advanced ovarian cancer: The MIID-SOC trial.

BACKGROUND: We sought to create a laparoscopic-based model to predict the ability to perform a minimally invasive (MIS) cytoreductive surgery in advanced epithelial ovarian cancer patients who have received neoadjuvant chemotherapy (NACT). METHODS: Fifty women were enrolled in a multi-institutional prospective pilot study (NCT03378128). Each patient underwent laparoscopic evaluation of 43 abdominopelvic sites followed by surgeon dictated surgical approach, either continue MIS or laparotomically. However, if the procedure continued MIS, the placement of a hand-assist port for manual palpation was mandated to emulate a laparotomic approach and all 43 sites were re-evaluated. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were calculated for each site to predict MIS resectability. Each parameter was assigned a numeric value based on the strength of statistical association and a total predictive index score (PIV) was assigned for each patient. Receiver operating characteristic curve analysis was used to assess the ability of the model to predict the MIS approach. RESULTS: Twenty-seven patients (61%) underwent MIS surgery. The following abdominopelvic sites were selected for inclusion in the model: gastrosplenic ligament, rectum, left mesocolon, transverse colon, right colon, cecum, appendix, liver capsule, intrahepatic fossa/gallbladder, ileum/jejunum. Using the PIV, a ROC was generated with an AUC = 0.695. In the final model, a PIV <2 identified patients able to undergo an optimal MIS cytoreductive surgery with an accuracy of 68.2%. The specificity, or the ability to identify patients who would not be able to undergo an optimal MIS interval cytoreductive surgery, was 66.7%. CONCLUSION: This predictive index model may help to guide future inclusion criteria in randomized studies evaluating the MIS approach in advanced epithelial ovarian cancer.

Opioid and benzodiazepine use in gynecologic oncology patients.

OBJECTIVE: The goals of this study were to describe opioid and benzodiazepine prescribing practices in the gynecologic oncology patient population and determine risks for opioid misuse in these patients. METHODS: Retrospective study of opioid and benzodiazepine prescriptions for patients treated for cervical, ovarian (including fallopian tube/primary peritoneal), and uterine cancers within a single healthcare system from January 2016 to August 2018. RESULTS: A total of 7643 prescriptions for opioids and/or benzodiazepines were dispensed to 3252 patients over 5754 prescribing encounters for cervical (n=2602, 34.1%), ovarian (n=2468, 32.3%), and uterine (n=2572, 33.7%) cancer. Prescriptions were most often written in an outpatient setting (51.0%) compared with inpatient discharge (25.8%). Cervical cancer patients were more likely to have received a prescription in an emergency department or from a pain/palliative care specialist (p=0.0001). Cervical cancer patients were least likely to have prescriptions associated with surgery (6.1%) compared with ovarian cancer (15.1%) or uterine cancer (22.9%) patients. The morphine milligram equivalents prescribed were higher for patients with cervical cancer (62.6) compared with patients with ovarian and uterine cancer (46.0 and 45.7, respectively) (p=0.0001). Risk factors for opioid misuse were present in 25% of patients studied; cervical cancer patients were more likely to have at least one risk factor present during a prescribing encounter (p=0.0001). Cervical cancer was associated with a higher number of risk factors (p<0.001). CONCLUSIONS: Opioid and benzodiazepine prescribing patterns differ for cervical, ovarian, and uterine cancer patients. Gynecologic oncology patients are overall at low risk for opioid misuse; however, patients with cervical cancer are more likely to have risk factors present for opioid misuse.

Molecular variations in uterine carcinosarcomas identify therapeutic opportunities.

OBJECTIVE: To perform comprehensive genomic profiling on a large cohort of patients with uterine carcinosarcomas to identify potential therapeutic targets. METHODS: Molecular profiling was conducted on 168 retrospectively de-identified patients with uterine carcinosarcomas using the Caris Life Sciences platform. Specimens were evaluated for aberrations in protein expression by immunohistochemistry, DNA sequence mutation using a 592-gene next generation sequencing panel, copy number amplification using next generation sequencing or in situ hybridization, and fusion events using NextGen RNA sequencing. Tumor mutational load and microsatellite instability were also evaluated. RESULTS: We identified 168 patients with uterine carcinosarcoma; median age of the cohort was 67 years. The most common mutations were observed in the following genes: TP53 (86%), PIK3CA (34%), FBXW7 (23%), PTEN (18%), KRAS (16%), PPP2R1A (10%). Tumor mutational load was low to moderate in most cases (50% and 45%, respectively). HER2/neu (ERBB2) was amplified in 9% of tumors. Immunohistochemistry protein expression was elevated in TOP2A (95%), TS (80%), PTEN (76%), and TUBB3 (66%). Mismatch repair deficiency was rare (4%). CONCLUSIONS: Multiple somatic mutations and copy number alterations in genes that are therapeutic targets were identified in half of cases. Uterine carcinosarcomas represent an aggressive histology with limited treatment options and poor outcomes, and clinical trials are needed to validate new therapeutic targets.

Physician pain and discomfort during minimally invasive gynecologic cancer surgery.

OBJECTIVE: Despite increasing awareness of physical strain to surgeons associated with minimally invasive surgery (MIS), its use continues to expand. We sought to gather information from gynecologic oncologists regarding physical discomfort due to MIS. METHODS: Anonymous surveys were e-mailed to 1279 Society of Gynecologic Oncology (SGO) members. Physical symptoms (numbness, pain, stiffness, and fatigue) and surgical and demographic factors were assessed. Univariate and multivariate analyses were performed to determine risk factors for physical symptoms. RESULTS: We analyzed responses of 350 SGO members who completed the survey and currently performed >50% of procedures robotically (n=122), laparoscopically (n=67), or abdominally (n=61). Sixty-one percent of members reported physical symptoms related to MIS. The rate of symptoms was higher in the robotic group (72%) than the laparoscopic (57%) or abdominal groups (49%) (p=0.0052). Stiffness (p=0.0373) and fatigue (p=0.0125) were more common in the robotic group. Female sex (p<0.0001), higher caseload (p=0.0007), and academic practice (p=0.0186) were associated with increased symptoms. On multivariate analysis, robotic surgery (odds ratio [OR] 2.38, 95% CI 1.20-4.69) and female sex (OR 4.20, 95% CI 2.13-8.29) were significant predictors of symptoms. There was no correlation between seeking treatment and surgical modality (laparotomy 11%, robotic 20%, laparoscopy 25%, p=0.12). CONCLUSIONS: Gynecologic oncologists report physical symptoms due to MIS at an alarming rate. Robotic surgery and female sex appear to be risk factors for physical discomfort. As we strive to improve patient outcomes and decrease patient morbidity with MIS, we must also work to improve the ergonomics of MIS for surgeons.

Concurrent carboplatin and paclitaxel with pelvic radiation therapy in the primary treatment of cervical cancer.

OBJECTIVE: The objective of the study was to determine the feasibility of weekly carboplatin/paclitaxel with radiation therapy (RT) in the primary treatment of cervical cancer. STUDY DESIGN: Women diagnosed with stage IB-1 to stage IVA untreated primary cervical cancer were eligible. Carboplatin (area under the curve = 2.0) and paclitaxel 40 mg/m2 were administered weekly for 6 weeks with pelvic RT. Brachytherapy was completed after pelvic RT. Acute toxicities and response to treatment were assessed. RESULTS: Twenty-two evaluable patients were enrolled. The median duration of follow-up was 23 months. Carboplatin (mean dose 245 mg) and paclitaxel (mean dose 70 mg) were successfully administered in 97% and 90% of planned treatments, respectively. Median time to complete external radiation therapy was 36.6 days (25-57 days). Grade 3/4 hematologic or gastrointestinal toxicity was unusual. The complete response rate 3 months after completion of therapy was 91%. The estimated 3-year progression-free survival is 70% and overall survival is 65%. CONCLUSION: Weekly carboplatin/paclitaxel and RT is a reasonable treatment regimen for cervical cancer.

Concurrent carboplatin with pelvic radiation therapy in the primary treatment of cervix cancer.

OBJECTIVES: The objectives were to determine the acute toxicities of concurrent carboplatin and radiation therapy in the primary treatment of cervix cancer and to ascertain the antitumor activity of this regimen. METHODS: Patients with stage IB-1 to IVA untreated primary cervix cancers were eligible for enrollment into this study. Carboplatin was administered on a weekly basis with external radiation therapy (ERT). Low-dose brachytherapy was given after completion of ERT. Acute toxicities and response to treatment were assessed. RESULTS: Thirty-one evaluable patients were enrolled. The majority of patients had early stage disease. Carboplatin was successfully administered in 175 out of 186 (94%) planned treatments. All patients completed the prescribed course of radiation therapy. The mean treatment time was 50 days (36-73). There were no treatment delays for neutropenia or gastrointestinal toxicity. No patient was hospitalized for treatment related toxicities. Gastrointestinal toxicity equivalent to grade 3 or 4 was not reported. The objective tumor response based on physical exam findings and computed tomography measurements was 90%. CONCLUSION: Patients with cervix cancer can be treated on schedule with concurrent carboplatin and pelvic radiation therapy. This regimen is well tolerated and produces excellent response rates.