A phase III, multicenter, randomized study of olvimulogene nanivacirepvec followed by platinum-doublet chemotherapy and bevacizumab compared with platinum-doublet chemotherapy and bevacizumab in women with platinum-resistant/refractory ovarian cancer.

BACKGROUND: Treatment options for patients with platinum-resistant/refractory ovarian cancers are limited and only marginally effective. The development of novel, more effective therapies addresses a critical unmet medical need. Olvimulogene nanivacirepvec (Olvi-Vec), with its strong immune modulating effect on the tumor microenvironment, may provide re-sensitization to platinum and clinically reverse platinum resistance or refractoriness in platinum-resistant/refractory ovarian cancer. PRIMARY OBJECTIVE: The primary objective is to evaluate the efficacy of intra-peritoneal Olvi-Vec followed by platinum-based chemotherapy and bevacizumab in patients with platinum-resistant/refractory ovarian cancer. STUDY HYPOTHESIS: This phase III study investigates Olvi-Vec oncolytic immunotherapy followed by platinum-based chemotherapy and bevacizumab as an immunochemotherapy evaluating the hypothesis that such sequential combination therapy will prolong progression-free survival (PFS) and bring other clinical benefits compared with treatment with platinum-based chemotherapy and bevacizumab. TRIAL DESIGN: This is a multicenter, prospective, randomized, and active-controlled phase III trial. Patients will be randomized 2:1 into the experimental arm treated with Olvi-Vec followed by platinum-doublet chemotherapy and bevacizumab or the control arm treated with platinum-doublet chemotherapy and bevacizumab. MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients must have recurrent, platinum-resistant/refractory, non-resectable high-grade serous, endometrioid, or clear-cell ovarian, fallopian tube, or primary peritoneal cancer. Patients must have had ≥3 lines of prior chemotherapy. PRIMARY ENDPOINT: The primary endpoint is PFS in the intention-to-treat population. SAMPLE SIZE: Approximately 186 patients (approximately 124 patients randomized to the experimental arm and 62 to the control arm) will be enrolled to capture 127 PFS events. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Expected complete accrual in 2024 with presentation of primary endpoint results in 2025. TRIAL REGISTRATION: NCT05281471.

Prominent decidualization following progestin treatment for endometrial hyperplasia and carcinoma as a mimic of large residual tumor: A cautionary tale.

OBJECTIVE: Progestin-based therapy is common for patients with endometrial neoplasia who desire fertility preservation, but some patients ultimately require surgery. Intraoperative assessment, which can use gross lesion size, may impact the extent of surgery performed. We sought to characterize the extent to which grossly identified lesions in the setting of progestin therapy correspond to microscopic findings. METHODS: Thirteen hysterectomy specimens with progestin-treated atypical hyperplasia or endometrioid carcinoma were identified. Clinicopathologic factors were collected by chart review. Slides were assessed for the extent to which decidualized stroma (DS) comprised grossly identified lesions and comparisons were drawn with tumor size, age, and menopausal status. RESULTS: Mass lesions were described in 11 cases with a median of 4.5 cm (range 1-8.2) and the 2 cases without discrete masses had diffuse thickening. Two patients had only focal residual hyperplasia despite having mass lesions (7 & 2.2 cm). DS was more prominent in premenopausal patients (median 65%, range 10-90%) than in postmenopausal patients (median 18%, range 10-40%; p = 0.06). The distribution of DS throughout mass lesions was variable. CONCLUSIONS: Large mass lesions following progestin therapy may histologically consist of DS with little to no residual neoplastic disease, such that perceived tumor size does not necessarily reflect extensive residual disease, especially in pre-menopausal patients. Intraoperative gross assessment alone may lead to unnecessary lymphadenectomy and/or oophorectomy, but this can potentially be prevented by using frozen section.

Using simple radiologic measurements to anticipate surgical challenge in endometrial cancer: a prospective study.

OBJECTIVES: To determine if linear measurements of adiposity from pre-operative imaging can improve anticipation of surgical difficulty among endometrial cancer patients. METHODS: Eighty patients with newly diagnosed endometrial cancer were enrolled. Routine pre-operative imaging (MRI or CT) was performed. Radiologic linear measurements of the following were obtained: anterior-to-posterior skin distance; anterior skin to anterior edge of L5 distance (total anterior); anterior peritoneum to anterior edge of L5 distance (visceral obesity); and posterior edge of L5 to posterior skin distance (total posterior). Surgeons completed questionnaires quantifying preoperative anticipated operative difficulty and postoperative reported operative difficulty. The primary objective was to assess for a correlation between linear measurements of visceral fat and reported operative difficulty. RESULTS: Seventy-nine patients had questionnaires completed, preoperative imaging obtained, and surgery performed. Univariate analysis showed all four linear measurements, body mass index, weight, and anticipated operative difficulty were associated with increased reported operative difficulty (P< 0.05). Multivariate analysis demonstrated that body mass index and linear measurements visceral obesity and total posterior were independently associated with increased reported operative difficulty (P< 0.05). Compared with body mass index, the visceral obesity measurement was more sensitive and specific for predicting increased reported operative difficulty (visceral obesity; sensitivity 54%, specificity 91 %; body mass index; sensitivity 38%, specificity 89%). A difficulty risk model combining body mass index, visceral obesity, and total posterior demonstrated better predictive performance than any individual preoperative variable. CONCLUSIONS: Simple linear measurements of visceral fat obtained from preoperative imaging are more predictive than body mass index alone in anticipating surgeon-reported operative difficulty. These easily obtained measurements may assist in preoperative decision making in this challenging patient population.

Preoperative obstructive sleep apnea screening in gynecologic oncology patients.

BACKGROUND: Women with a gynecologic cancer tend to be older, obese, and postmenopausal, characteristics that are associated with an increased risk for obstructive sleep apnea. However, there is limited investigation regarding the condition's prevalence in this population or its impact on postoperative outcomes. In other surgical populations, patients with obstructive sleep apnea have been observed to be at increased risk for adverse postoperative events. OBJECTIVE: We sought to estimate the prevalence of obstructive sleep apnea among gynecologic oncology patients undergoing elective surgery and to investigate for a relationship between obstructive sleep apnea and postoperative outcomes. STUDY DESIGN: Patients referred to an academic gynecologic oncology practice were approached for enrollment in this prospective, observational study. Patients were considered eligible for study enrollment if they were scheduled for a nonemergent inpatient surgery and could provide informed consent. Enrolled patients were evaluated for a preexisting diagnosis of obstructive sleep apnea. Those without a prior diagnosis were screened using the validated, 4-item STOP questionnaire (ie, Snore loudly, daytime Tiredness, Observed apnea, elevated blood Pressure). All patients who screened positive for obstructive sleep apnea were referred for polysomnography. The primary outcome was the prevalence of women with obstructive sleep apnea or those who screened at high risk for the condition. Secondary outcomes examined the correlation between body mass index (kg/m2) with obstructive sleep apnea and assessed for a relationship between obstructive sleep apnea and postoperative outcomes. RESULTS: Over a 22-month accrual period, 383 eligible patients were consecutively approached to participate in the study. A cohort of 260 patients were enrolled. A total of 33/260 patients (13%) were identified as having a previous diagnosis of obstructive sleep apnea. An additional 66/260 (25%) screened at risk for the condition using the STOP questionnaire. Of the patients who screened positive, 8/66 (12%) completed polysomnography, all of whom (8/8 [100%]) were found to have obstructive sleep apnea. The prevalence of previously diagnosed obstructive sleep apnea or screening at risk for the condition increased as body mass index increased (P < .001). Women with untreated obstructive sleep apnea and those who screened at risk for the condition were found to have an increased risk for postoperative hypoxemia (odds ratio, 3.5; 95% confidence interval, 1.8-4.7; P = .011) and delayed return of bowel function (odds ratio, 2.1; 95% confidence interval, 1.3-4.5; P = .009). CONCLUSION: The prevalence of obstructive sleep apnea or screening at risk for the condition is high among women presenting for surgery with a gynecologic oncologist. Providers should consider evaluating a patient's risk for obstructive sleep apnea in the preoperative setting, especially when risk factors for the condition are present.

Thrombocytosis is Predictive of Postoperative Pulmonary Embolism in Patients With Gynecologic Cancer.

OBJECTIVES: The prompt diagnosis of postoperative pulmonary embolism (PE) in gynecologic oncology patients is imperative, but the clinical presentation is nonspecific in this high-risk group. We sought to determine risk factors and clinical findings that may assist clinicians in diagnosing PE in the inpatient setting. METHODS: Radiology data were queried to identify patients with gynecologic cancer who had a postoperative PE evaluation with computed tomography pulmonary angiography (CT-PA). Patient clinical findings at the time of the PE evaluation were abstracted, and univariate and multivariate regression analyses were performed to identify predictors of PE. RESULTS: For 6 years, there were 2498 major gynecologic oncology surgical procedures performed at our institution. Within 14 days of surgery, 107 CT-PA studies were obtained with a positive study rate of 24.3%. In patients with and without PE, there was no significant difference noted for age, oxygen saturations, body mass index and heart rate. After controlling for stage, history of venous thromboembolism (VTE), heart rate, and oxygen saturation, platelet count (odds ratio, 1.26 per 50 counts increase; 95% confidence interval, 1.07-1.48; P = 0.006) and history of VTE (odds ratio, 17.1; 95% confidence interval, 1.77-Inf, P = 0.014) were identified as independent predictors of PE in the multivariate model. CONCLUSIONS: Although clinicians often use tachycardia and low oxygen saturation as triggers to order PE imaging studies, these signs have a very low specificity. Given the findings of our study, accounting for high platelet count and history of VTE increases the pretest probability of CT-PA study.

Risk factors for early-occurring and late-occurring incisional hernias after primary laparotomy for ovarian cancer.

OBJECTIVE: To evaluate a cohort of gynecologic oncology patients to discover risk factors for early- and late-occurring incisional hernia after midline incision for ovarian cancer. METHODS: We collected retrospective data from patients undergoing primary laparotomy for ovarian cancer at the University of Wisconsin Hospitals and Clinics from 2001 to 2007. Patient characteristics and potential risk factors for hernia formation were noted. Physical examination, abdominal computerized assisted tomography scans, or both were used to detect hernias 1 year after surgery (early hernia) and 2 years after surgery (late hernia). RESULTS: There were 265 patients available for the 1-year analysis and 189 patients for the 2-year analysis. Early and late hernia formation occurred in 9.8% (95% confidence interval [CI] 6.2-12%) and an additional 7.9% (95% CI 4.1-12%) of patients, respectively. Using multiple logistic regression, poor nutritional status (albumin less than 3 g/dL) and suboptimal cytoreductive surgery (1 cm or greater residual tumor) were significantly associated with the formation of early incisional hernia after midline incision (P<.001 for both). Late hernia formation was associated only with age 65 years or older (P=.01). CONCLUSION: The formation of early incisional hernias after midline incision is associated with poor nutritional status and suboptimal cytoreductive surgery, whereas late hernia formation is associated with advanced age.

Intensive postoperative glucose control reduces the surgical site infection rates in gynecologic oncology patients.

OBJECTIVE: SSI rates after gynecologic oncology surgery vary from 5% to 35%, but are up to 45% in patients with diabetes mellitus (DM). Strict postoperative glucose control by insulin infusion has been shown to lower morbidity, but not specifically SSI rates. Our project studied continuous postoperative insulin infusion for 24h for gynecologic oncology patients with DM and hyperglycemia with a target blood glucose of <139 mL/dL and a primary outcome of the protocol's impact on SSI rates. METHODS: We compared SSI rates retrospectively among three groups. Group 1 was composed of patients with DM whose blood glucose was controlled with intermittent subcutaneous insulin injections. Group 2 was composed of patients with DM and postoperative hyperglycemia whose blood glucose was controlled by insulin infusion. Group 3 was composed of patients with neither DM nor hyperglycemia. We controlled for all relevant factors associated with SSI. RESULTS: We studied a total of 372 patients. Patients in Group 2 had an SSI rate of 26/135 (19%), similar to patients in Group 3 whose rate was 19/89 (21%). Both were significantly lower than the SSI rate (43/148, 29%) of patients in Group 1. This reduction of 35% is significant (p = 0.02). Multivariate analysis showed an odd ratio = 0.5 (0.28-0.91) in reducing SSI rates after instituting this protocol. CONCLUSIONS: Initiating intensive glycemic control for 24h after gynecologic oncology surgery in patients with DM and postoperative hyperglycemia lowers the SSI rate by 35% (OR = 0.5) compared to patients receiving intermittent sliding scale insulin and to a rate equivalent to non-diabetics.

Angiosarcoma originating from an ovarian mature teratoma, a rare disease with complex treatment modalities.

► Ovarian angiosarcomas are rare and clinically aggressive neoplasms. ► In addition to surgery, taxol is the most studied adjuvant chemotherapy. ► Anti-angiogenic therapies can be considered as an option.

Uterine artery sparing robotic radical trachelectomy (AS-RRT) for early cancer of the cervix.

OBJECTIVE: To describe the surgical technique of uterine artery sparing robotic assisted radical trachelectomy (AS-RRT) for early stage cervical cancer. METHODS: We used our experience with AS-RRT performed at the University of Wisconsin-Carbone Comprehensive Cancer Center, USA, to present a detailed description of the surgical technique. RESULTS: The report details, step-by-step, our innovative surgical technique, supported by photos and illustrations. We also discuss potential difficulties with the surgical technique and offer solutions. CONCLUSION: Technically, the surgery is feasible and could be performed by any gynecologic oncologist who is skilled in radical pelvic surgery and the robotic system. The long-term obstetric and oncologic outcome of this technique would be expected to match the outcome of the other radical trachelectomy techniques in the published literature, but is yet to be fully elucidated.