Gynecologic cancer care in the first year of the COVID-19 pandemic.

OBJECTIVE: To analyze the impact of the early COVID-19 pandemic on the diagnosis and initiation of treatment for patients with gynecologic cancer. METHODS: Patients diagnosed with gynecologic cancer in the National Cancer Database during 2017-2020 were included. For the first aim, incidence rate ratios were calculated to compare gynecologic cancer diagnosis in the first year of the COVID-19 pandemic to the three years prior, and factors associated with a reduction in diagnosis were identified. For the second aim, patients who experienced an 8-week delay in cancer treatment were compared to those who did not. Multivariate logistic regression was used to identify factors associated with treatment delay. Propensity score analysis was utilized to compare the rate of cancer treatment delay in patients who were diagnosed with COVID-19 to those who were not. RESULTS: The incidence rate ratio of being diagnosed with gynecologic cancer in 2020 versus 2017-2019 was 0.90 (95%CI 0.90-0.91). Factors associated with increased risk of missed or delayed diagnosis in 2020 included cervical cancer, earlier cancer stage, younger age, lower levels of medical comorbidity, and lack of health insurance. In 2020, factors associated with treatment delay included COVID-19 diagnosis (aOR 1.50, 95%CI 1.35-1.67), in addition to race and ethnicity, insurance type, comorbidity, cancer stage, and primary site. The risk of treatment delay remained significantly elevated in patients diagnosed with COVID-19 after propensity-score matching. CONCLUSIONS: Gynecologic cancer diagnosis and timely provision of care were negatively impacted during the first year of the COVID-19 pandemic, with certain subgroups at elevated risk.

Efficacy and Safety of Pembrolizumab in Combination With Bevacizumab and Oral Metronomic Cyclophosphamide in the Treatment of Recurrent Ovarian Cancer: A Phase 2 Nonrandomized Clinical Trial.

IMPORTANCE: Treatment options for recurrent ovarian cancer are of limited clinical benefit and adversely affect patient quality of life, representing an unmet need for tolerable effective therapies. OBJECTIVE: To assess the efficacy and safety of a combination of pembrolizumab with bevacizumab and oral metronomic cyclophosphamide in patients with recurrent platinum-sensitive, platinum-resistant, or refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer. DESIGN, SETTING, AND PARTICIPANTS: This open-label, single-arm phase 2 cohort study enrolled patients from September 6, 2016, to June 27, 2018, at a single institution in the United States. Eligible patients had recurrent ovarian cancer, measurable disease per immune-related Response Evaluation Criteria In Solid Tumors (irRECIST), and Eastern Cooperative Oncology Group performance status of 0 to 1. Data were analyzed from September 6, 2016, to February 20, 2020. INTERVENTIONS: Patients received intravenous pembrolizumab, 200 mg, and bevacizumab, 15 mg/kg, every 3 weeks and oral cyclophosphamide, 50 mg, once daily during the treatment cycle until disease progression, unacceptable toxic effects, or withdrawal of consent. MAIN OUTCOMES AND MEASURES: Primary outcomes were objective response rate (ORR) and progression-free survival (PFS). RESULTS: Of the 40 women enrolled, 30 (75.0%) had platinum-resistant and 10 (25.0%) had platinum-sensitive ovarian cancer with a mean (SD) age of 62.2 (9.4) years. Three women (7.5%) had complete responses, 16 (40.0%) had partial responses, and 19 (47.5%) had stable disease in response to treatment based on irRECIST criteria, with an ORR of 47.5%, clinical benefit in 38 (95.0%), and durable response in 10 (25.0%). Median PFS was 10.0 (90% CI, 6.5-17.4) months. The most common grade 3 to 4 treatment-related adverse events were hypertension (6 [15.0%]) and lymphopenia (3 [7.5%]). The most frequently reported adverse events included fatigue (18 [45.0%]), diarrhea (13 [32.5%]), and hypertension (11 [27.5%]). CONCLUSIONS AND RELEVANCE: In this phase 2 nonrandomized clinical trial, the combination of pembrolizumab with bevacizumab and oral cyclophosphamide was well tolerated and demonstrated clinical benefit in 95.0% and durable treatment responses (>12 months) in 25.0% of patients with recurrent ovarian cancer. This combination may represent a future treatment strategy for recurrent ovarian cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02853318.

Immunotherapy for Gynecologic Cancer: Current Applications and Future Directions.

The role of the immune system in the development of cancer has been a subject of ongoing clinical investigation in recent years. Emerging data demonstrate that tumorigenesis resulting in ovarian, uterine, and cervical cancers is a consequence of impaired host immune responses to cancerous cells. Leveraging the immune system through the use of immune checkpoint inhibitors, therapeutic vaccine therapy, and adoptive cell transfer presents a profound opportunity to revolutionize cancer treatment. This review will encompass the role of the immune system in development of gynecologic cancers and highlight recent data regarding immunotherapy applications in ovarian, uterine, and cervical cancers.

Implementation of a restrictive blood transfusion protocol in a gynecologic oncology service.

OBJECTIVES: The purpose of this study was to evaluate the impact of a restrictive blood transfusion protocol in a postoperative gynecologic oncology population. The primary objective was the rate of blood transfusions after surgery before and after implementation of a restrictive transfusion protocol (from July 1st 2011 to December 30th 2016). Secondary outcomes were patient morbidity and included rates of surgical site infection, pneumonia, sepsis, unplanned intubation, prolonged ventilator use, renal insufficiency, acute renal failure, urinary tract infection, cerebral vascular accident, cardiac complications, venous thromboembolism, and death within 30 days of surgery, readmissions and length of stay. METHODS: A restrictive blood transfusion protocol was implemented by the gynecologic oncology service at a National Comprehensive Cancer Network designated Comprehensive Cancer Center on January 1st, 2014. The restrictive protocol required that no patient receive a blood transfusion for hemoglobin greater than 7.0 g/dL (or hematocrit greater than 21.0%) and that all red blood cells were administered in one unit increments followed by re-evaluation of blood parameters. Exceptions to this protocol were postoperative symptomatic anemia, intraoperative or day of surgery transfusion, active bleeding, postoperative severe sepsis, postoperative active coronary ischemia, and postoperative transfusion after 1.5 liter or greater blood loss. RESULTS: 1482 patients were identified for this study (755 in the pre-protocol group and 727 in the post-protocol group). Patients treated under the restrictive protocol had decreased rates of red blood cell transfusion (11.0% vs 5.9% p<0.001), superficial surgical site infection (7.7% vs 4.1% p=0.005), deep surgical site infection (2.3% vs 0.7% p=0.02), and median length of stay (3.0 days vs 2.0 days p<0.001). CONCLUSIONS: A restrictive blood transfusion protocol is associated with reductions in the rates of blood transfusions and postoperative morbidity with a 46.8% reduction in superficial surgical site infection and a 69.6% decrease in deep surgical site infection in the gynecologic oncology patient population.

Efficacy of Hyperthermic Intraperitoneal Chemotherapy and Cytoreductive Surgery in the Treatment of Recurrent Uterine Sarcoma.

OBJECTIVE: Uterine sarcomas (USs) are characterized by poor response to systemic chemotherapy and high recurrence rates. This study evaluates whether the use of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) confers survival benefit in comparison with conventional treatment modalities in patients with recurrent US. METHODS/MATERIALS: A retrospective analysis of patients with recurrent US at a single institution for an 11-year study period was performed. All women with a pathologic diagnosis of leiomyosarcoma, adenosarcoma, endometrial stromal sarcoma, or undifferentiated US were identified. Overall and disease-free survival was estimated using Kaplan-Meier method. Comparisons between the study groups were performed with the log-rank test and Cox regression. RESULTS: A total of 26 patients were identified. Five patients received chemotherapy and/or radiotherapy without surgical intervention, 14 patients underwent surgery alone or a combination of surgery and adjuvant systemic chemotherapy, and 7 patients received cytoreductive surgery with HIPEC. There was no treatment-related mortality in any group, and only 1 patient had grade III-IV surgical complications. Median disease-free survival was 2.4 months for patients with nonsurgical treatments, 5.3 months for patients treated with conventional surgery, and 11.3 months for patients treated with HIPEC. Median overall survival was 35.9 months for patients treated with conventional surgery and 43.8 months for patients treated with HIPEC. CONCLUSIONS: Our study is the first to compare survival outcomes of HIPEC versus conventional therapies for recurrent US and is suggestive of treatment benefit. Further studies with more patients and longer follow-up to evaluate the role of HIPEC in management of this disease are warranted.

Ultrarestrictive Opioid Prescription Protocol for Pain Management After Gynecologic and Abdominal Surgery.

Importance: Opioids are routinely prescribed for postoperative home pain management for most patients in the United States, with limited evidence of the amount needed to be dispensed. Opioid-based treatment often adversely affects recovery. Prescribed opioids increase the risk of chronic opioid use, abuse, and diversion and contribute to the current opioid epidemic. Objective: To evaluate whether after hospital discharge, postsurgical acute pain can be effectively managed with a markedly reduced number of opioid doses. Design, Setting, and Participants: In this case-control cohort study, an ultrarestrictive opioid prescription protocol (UROPP) was designed and implemented from June 26, 2017, through June 30, 2018, at a single tertiary-care comprehensive cancer center. All patients undergoing gynecologic oncology surgery were included. Patients undergoing ambulatory or minimally invasive surgery (laparoscopic or robotic approach) were not prescribed opioids at discharge unless they required more than 5 doses of oral or intravenous opioids while in the hospital. Patients who underwent a laparotomy were provided a 3-day opioid pain medication supply at discharge. Main Outcomes and Measures: Total number of opioid pain medications prescribed in the 60-day perioperative period, requests for opioid prescription refills, and postoperative pain scores and complications were evaluated. Factors associated with increased postoperative pain, preoperative and postoperative pain scores, inpatient status, prior opioid use, and all opioid prescriptions within the 60-day perioperative window were monitored among the case patients and compared with those from consecutive control patients treated at the center in the 12 months before the UROPP was implemented. Results: Patient demographics and procedure characteristics were not statistically different between the 2 cohorts of women (605 cases: mean [SD] age, 56.3 [14.5] years; 626 controls: mean [SD] age, 55.5 [13.9] years). The mean (SD) number of opioid tablets given at discharge after a laparotomy was 43.6 (17.0) before implementation of the UROPP and 12.1 (8.9) after implementation (P < .001). For patients who underwent laparoscopic or robotic surgery, the mean (SD) number of opioid tablets given at discharge was 38.4 (17.4) before implementation of the UROPP and 1.3 (3.7) after implementation (P < .001). After ambulatory surgery, the mean (SD) number of opioid tablets given at discharge was 13.9 (16.6) before implementation of the UROPP and 0.2 (2.1) after implementation (P < .001). The mean (SD) perioperative oral morphine equivalent dose was reduced to 64.3 (207.2) mg from 339.4 (674.4) mg the year prior for all opioid-naive patients (P < .001). The significant reduction in the number of dispensed opioids was not associated with an increase the number of refill requests (104 patients [16.6%] in the pre-UROPP group vs 100 patients [16.5%] in the post-UROPP group; P = .99), the mean (SD) postoperative visit pain scores (1.1 [2.2] for the post-UROPP group vs 1.4 [2.3] for pre-UROPP group; P = .06), or the number of complications (29 cases [4.8%] in the post-UROPP group vs 42 cases [6.7%] in the pre-UROPP group; P = .15). Conclusions and Relevance: Implementation of a UROPP was associated with a significant decrease in the overall amount of opioids prescribed to patients after gynecologic and abdominal surgery at the time of discharge for all patients, and for the entire perioperative time for opioid-naive patients without changes in pain scores, complications, or medication refill requests.

Primary Placement of Incisional Negative Pressure Wound Therapy at Time of Laparotomy for Gynecologic Malignancies.

OBJECTIVE: Wound complications are an important cause of postoperative morbidity amongst patient with gynecologic malignancies. We evaluated whether the placement of prophylactic negative pressure wound therapy (NPWT) at the time of laparotomy for gynecologic cancer surgery reduces wound complication rates. METHODS: A retrospective analysis of patients undergoing laparotomy with primary wound closure performed by a gynecologic oncologist at a single academic institution over a 5-year study period was performed. Patients who had placement of prophylactic NPWT dressing were compared with patients with a standard closure. Postoperative outcomes were examined. RESULTS: A total of 230 patients were identified: 208 women received standard wound care, 22 received NPWT. Groups were similar in age, prevalence of diabetes, tobacco use, and number of previous abdominal procedures. Intraoperative factors including length of procedure and transfusion requirements were similar. Body mass index for patients receiving standard treatment was 30.67 compared with 41.29 for NPWT group (P < 0.001). Incidence of all wound complications was 19.7% for those receiving standard treatment versus 27.3% for NPWT group (P = 0.40). Length of hospital stay was similar between the 2 groups (5.25 vs 6.22 days, P = 0.20). There were 3 hospital readmissions for wound complications-none occurred in women with a prophylactic NPWT dressing. CONCLUSIONS: Despite significantly higher obesity rates, patients with prophylactic NPWT dressing placement had similar rates of wound complications. Our findings suggest a potential therapeutic benefit in the use of prophylactic NPWT for the reduction of wound complications in this high-risk gynecologic oncology patient population.

Risk, risk reduction and management of occult malignancy diagnosed after uterine morcellation: a commentary.

Minimally invasive surgical techniques compared with laparotomy offer the advantages of less intraoperative blood loss, shorter hospitalization, fewer wound complications and faster return to baseline activity for both hysterectomy and myomectomy. While morcellation allows for the laparoscopic removal of large specimens, it may result in intraperitoneal dissemination of benign disease or upstaging of occult malignancy leading to compromised survival. There has been heightened scrutiny over appropriate patient selection and preoperative assessment in light of recent warnings against power morcellation issued by the US FDA. This commentary therefore summarizes the magnitude of such risks associated with uterine morcellation, current national regulatory statements and potential merits of risk-reducing approaches such as contained morcellation. The importance of patient counseling is underscored.