Clinical Activity of Olvimulogene Nanivacirepvec-Primed Immunochemotherapy in Heavily Pretreated Patients With Platinum-Resistant or Platinum-Refractory Ovarian Cancer: The Nonrandomized Phase 2 VIRO-15 Clinical Trial.

Importance: Patients with platinum-resistant or platinum-refractory ovarian cancer (PRROC) have limited therapeutic options, representing a considerable unmet medical need. Objective: To assess antitumor activity and safety of intraperitoneal (IP) olvimulogene nanivacirepvec (Olvi-Vec) virotherapy and platinum-based chemotherapy with or without bevacizumab in patients with PRROC. Design, Setting, and Participants: This open-label, nonrandomized multisite phase 2 VIRO-15 clinical trial enrolled patients with PRROC with disease progression following their last prior line of therapy from September 2016 to September 2019. Data cutoff was on March 31, 2022, and data were analyzed between April 2022 and September 2022. Interventions: Olvi-Vec was administered via a temporary IP dialysis catheter as 2 consecutive daily doses (3 × 109 pfu/d) followed by platinum-doublet chemotherapy with or without bevacizumab. Main Outcomes and Measures: Primary outcomes were objective response rate (ORR) via Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) and cancer antigen 125 (CA-125) assay, and progression-free survival (PFS). Secondary outcomes included duration of response (DOR), disease control rate (DCR), safety, and overall survival (OS). Results: Twenty-seven heavily pretreated patients with platinum-resistant (n = 14) or platinum-refractory (n = 13) ovarian cancer were enrolled. The median (range) age was 62 (35-78) years. The median (range) prior lines of therapy were 4 (2-9). All patients completed both Olvi-Vec infusions and chemotherapy. Median follow-up duration was 47.0 months (95% CI, 35.9 months to NA). Overall, ORR by RECIST 1.1 was 54% (95% CI, 33%-74%), with a DOR of 7.6 months (95% CI, 3.7-9.6 months). The DCR was 88% (21/24). The ORR by CA-125 was 85% (95% CI, 65%-96%). Median PFS by RECIST 1.1 was 11.0 months (95% CI, 6.7-13.0 months), and the PFS 6-month rate was 77%. Median PFS was 10.0 months (95% CI, 6.4-NA months) in the platinum-resistant group and 11.4 months (95% CI, 4.3-13.2 months) in the platinum-refractory group. The median OS was 15.7 months (95% CI, 12.3-23.8 months) in all patients, with a median OS of 18.5 months (95% CI, 11.3-23.8 months) in the platinum-resistant group and 14.7 months (95% CI, 10.8-33.6 months) in the platinum-refractory group. Most frequent treatment-related adverse events (TRAEs) (any grade, grade 3) were pyrexia (63.0%, 3.7%, respectively) and abdominal pain (51.9%, 7.4%, respectively). There were no grade 4 TRAEs, and no treatment-related discontinuations or deaths. Conclusions and Relevance: In this phase 2 nonrandomized clinical trial, Olvi-Vec followed by platinum-based chemotherapy with or without bevacizumab as immunochemotherapy demonstrated promising ORR and PFS with a manageable safety profile in patients with PRROC. These hypothesis-generating results warrant further evaluation in a confirmatory phase 3 trial. Trial Registration: ClinicalTrials.gov Identifier: NCT02759588.

A Rare Case of Idiopathic Pyometra in a Premenopausal Patient.

Pyometra is a very uncommon disease principally occurring in postmenopausal women. It is characterized by the accumulation of purulent material within the uterine cavity. This paper presents the clinical history of a 35-year-old premenopausal woman with otherwise normal menstruation who developed heavy menstruation and was diagnosed with a benign pyometra of indeterminate etiology in March 2017. The patient underwent repeated ultrasound-guided drainage, dilation and curettage, and antibiotic therapy. Biopsies of the pelvic sidewall revealed endometriosis in June 2017. The heavy menstruation and suppurative fluid in the uterus of the patient persisted in which intramuscular leuprolide acetate was prescribed to address the endometriosis and heavy menstrual bleeding. Ultimately, the leuprolide acetate effectively resolved the patient's bleeding and pyometra. The medication was concluded after 12 months of supervision and the patient is currently symptom free. Pyometra is an unusual condition rarely identified in premenopausal women. Drainage and antibiotic therapy are routinely employed; however, one may consider gonadotropin-releasing hormone agonist medication to potentially confer a beneficial patient outcome in rare cases where endometriosis and bleeding are intractable.

Pronounced clinical response following the oncolytic vaccinia virus GL-ONC1 and chemotherapy in a heavily pretreated ovarian cancer patient.

Heavily pretreated ovarian cancer patients become progressively chemoresistant, and thereafter, only scant treatments potentially accord reasonable, albeit limited clinical efficacy. We describe a case involving a 67-year-old ovarian cancer patient who underwent multiple lines of chemotherapy and presented with recurrent disease and a CA-125 of 4112 U/mL. Thenceforth, she was treated with GL-ONC1 oncolytic viral therapy that was administered laparoscopically in accordance with a clinical trial. The patient subsequently received chemotherapy and during the fourth cycle, her CA-125 decreased to 99 U/mL; moreover, a computed tomography scan of the pelvis exhibited significant disease reduction. Viral therapy hypothetically confers significant promise in the treatment of recurrent ovarian cancer, especially in patients who remain unresponsive to traditional medications.

The incidence of occult malignancy following uterine morcellation: A ten-year single institution experience retrospective cohort study.

INTRODUCTION: When the Food and Drug Administration (FDA) initially reported on the parlous incidence (0.28%) of occult malignancy identified following uterine power morcellation, investigations thereafter documented their particular experience with this surgical procedure. Nevertheless, the precise risk of identifying a sarcoma following uterine morcellation remains indeterminate, primarily due to varying study patient risk factors, diagnostic criteria and operative approach. METHOD: We retrospectively evaluated subjects who underwent an endoscopic hysterectomy and uterine power morcellation for the treatment of a presumptive, benign indication from January 2006 until December 2015. The primary outcome was the incidence of an occult malignancy. Secondarily, we were interested in characterizing the patients' specific clinical (age, menopausal status, body mass index (BMI)) risk factors within the context of a confirmed malignant or pre-malignant pathology. RESULTS: We identified 281 patients who underwent endoscopic surgery that incorporated uterine morcellation. During the study period, one subject was ultimately diagnosed with a uterine leiomyosarcoma; the overall incidence of occult malignancy was 0.36%. There were also 3 cases of uterine premalignant disease on final pathology (2 patients had complex hyperplasia with or without atypia and 1 subject was diagnosed with a smooth muscle tumor of uncertain malignant potential (an incidence of 1.1%)). We were unable to establish any relationship between patient age, uterine weight, menopausal status or BMI and the incidence of a malignant or pre-malignant pathology (P > 0.05). CONCLUSION: The rate of occult malignancy in the present investigation was similar to previously documented studies and that which has been reported by the FDA. Additional study of methods in which to enhance preoperative work-up and mitigate the surgical risk for tumor cell dissemination is warranted.

The safety and feasibility of minimally invasive sentinel lymph node staging using indocyanine green in the management of endometrial cancer.

OBJECTIVES: The purpose of this study was to report on the feasibility of laparoscopic sentinel lymph node (SLN) staging using indocyanine green (ICG) in the management of endometrial cancer. STUDY DESIGN: We retrospectively evaluated the charts of presumed, clinical stage I endometrial cancer patients who underwent robotic-assisted surgery that incorporated mapping with ICG and SLN dissection from January 2016 until February 2017. Patient demographics, operative characteristics (e.g., complications, lymph node counts) and pathology data were evaluated. RESULTS: There were 87 patients who were included in the study. A total of 370 lymph nodes were removed, of which 245 were SLNs; unilateral and bilateral mapping of the SLNs was achieved in 84 (96.5%) and 71 (81.6%) of subjects, respectively. There were 10 (11.5%) patients who had metastatic disease identified within 22 (5.9%) of the total (n = 370) lymph nodes extracted, 19 (7.7%) of which were sentinel lymph nodes. We did not observe any intraoperative complications. CONCLUSION: The results from our study suggest that minimally invasive SLN staging using ICG is a feasible procedure that is potentially effective at detecting metastases, which may ultimately attenuate the incidence of surgical morbidity.

Consolidation hyperthermic intraperitoneal chemotherapy for the treatment of advanced stage ovarian carcinoma: a 3 year experience.

PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) potentially confers significant survival benefits in the management of ovarian cancer although the long-term data remain scant. We sought to compare the survival rates of advanced stage ovarian cancer patients who were treated with primary induction therapy alone or in conjunction with consolidation HIPEC. METHODS: 69 ovarian cancer patients who underwent surgery and completed their primary induction chemotherapy were treated with consolidation carboplatin (AUC 10) based HIPEC and compared to a historical cohort that received surgery and primary chemotherapy alone (n = 69). The demographic and clinical characteristics on which we were primarily focused, included patient age, body mass index, surgery and pathology data, chemotherapy regimen, toxicity, and progression free/overall survival. RESULTS: The two patient groups' demographic and clinical characteristics were similar (P > 0.05). Progression-free survival was significantly more pronounced in the HIPEC (25.1 months) patients compared to the control group (20 months) (P = 0.024) and there was a decreased risk of disease progression accorded to the patients treated with HIPEC (HR 2.1028; 95% CI 1.2941-3.4167; P = 0.0027). However, we did not discern any HIPEC related overall survival advantages (P = 0.29). CONCLUSIONS: The results from our ovarian cancer study suggest that adjunctive HIPEC proffers a significant progression-free survival advantage and a decreased risk for disease progression. There was, however, no overall survival advantage discerned by the HIPEC group. We also recognize that HIPEC remains controversial, and thus randomized studies evaluating HIPEC compared to standard chemotherapy in the management of ovarian cancer are warranted.

The impact of total parenteral nutrition on postoperative recovery in patients treated for advanced stage ovarian cancer.

OBJECTIVES: Total parenteral nutrition (TPN) presumably benefits cancer patients although reports have disputed the significance of this nutritional intervention. We sought to compare the postoperative outcomes of ovarian cancer patients treated with either TPN or conservative management. METHODS: We retrospectively evaluated the impact of TPN and conservative management in ovarian cancer patients who underwent debulking surgery and a bowel resection. The primary study variables encompassed patient time until restoration of bowel function, number of postoperative complications and duration of hospital stay. RESULTS: There were 147 subjects who were selected for this study. The patients who were treated with TPN (n = 69) demonstrated a longer time until restoration of bowel function (5.77 vs. 4.70 days; P < 0.001), experienced lower pre-operative albumin levels (2.22 vs. 2.97 g/dL; P < 0.001) and endured a significantly longer hospital stay (11.46 vs. 7.14 days; P < 0.001) compared to the conservative management (n = 78) cohort. CONCLUSIONS: Postoperative TPN in ovarian cancer patients may be inadvisable because of the increased risk for complications. Moreover, in the hypoalbuminemic patients, TPN may have not only delayed their postoperative recovery and increased hospital stay duration, but further precipitated the manifestation of nosocomial sequelae.

Synuclein-γ (SNCG) expression in ovarian cancer is associated with high-risk clinicopathologic disease.

BACKGROUND: Synuclein gamma (SNCG) expression is associated with advanced disease and chemoresistance in multiple solid tumors. Our goal was to determine if SNCG protein expression in ovarian cancer was correlated with clinicopathologic variables and patient outcomes. METHODS: Tissue microarrays from primary tumors of 357 ovarian, fallopian tube, and primary peritoneal cancer patients, who underwent primary surgery at Roswell Park Cancer Institute between 1995 and 2007, were immunohistochemically stained for SNCG. A pathologist blinded to patient data scored tumors as positive if ≥10 % of the sample stained for SNCG. Medical records were reviewed for clinicopathologic and demographic variables. Between the positive and negative groups, Wilcoxon rank-sum test was used to compare the median ages and Fisher's exact test was used to compare groups in categorical variables. Cox proportional hazard models examined associations between SNCG and overall and progression-free survival. RESULTS: The median follow-up was 36 months, median overall survival was 39 months, and median progression-free survival was 18 months. SNCG presence was associated with clinical variables of serous histology, grade 3 disease, suboptimal debulking, ascites at surgery, FIGO stage III-IV cancer, or initial CA-125 level >485. There was no significant difference in overall survival (HR 1.06 95 % CI 0.81-1.39 P 0.69) or progression-free survival (HR 1.16 95 % CI 0.89-1.50 P 0.28) for patients with or without SNCG expression. CONCLUSIONS: SNCG expression in ovarian cancer is frequent in patients with high-risk features, but it does not correlate with chemotherapy response, overall survival, or progression-free survival.

Minimally invasive surgery in gynecologic oncology.

Minimally invasive surgery has been utilized in the field of obstetrics and gynecology as far back as the 1940s when culdoscopy was first introduced as a visualization tool. Gynecologists then began to employ minimally invasive surgery for adhesiolysis and obtaining biopsies but then expanded its use to include procedures such as tubal sterilization (Clyman (1963), L. E. Smale and M. L. Smale (1973), Thompson and Wheeless (1971), Peterson and Behrman (1971)). With advances in instrumentation, the first laparoscopic hysterectomy was successfully performed in 1989 by Reich et al. At the same time, minimally invasive surgery in gynecologic oncology was being developed alongside its benign counterpart. In the 1975s, Rosenoff et al. reported using peritoneoscopy for pretreatment evaluation in ovarian cancer, and Spinelli et al. reported on using laparoscopy for the staging of ovarian cancer. In 1993, Nichols used operative laparoscopy to perform pelvic lymphadenectomy in cervical cancer patients. The initial goals of minimally invasive surgery, not dissimilar to those of modern medicine, were to decrease the morbidity and mortality associated with surgery and therefore improve patient outcomes and patient satisfaction. This review will summarize the history and use of minimally invasive surgery in gynecologic oncology and also highlight new minimally invasive surgical approaches currently in development.