Use and Outcomes of Dexamethasone in the Management of Malignant Small Bowel Obstruction.

Objective: To describe rates of dexamethasone use in the nonoperative management of malignant small bowel obstruction (mSBO) and their outcomes. Background: mSBO is common in patients with advanced abdominal-pelvic cancers. Management includes prioritizing quality of life and avoiding surgical intervention when possible. The use of dexamethasone to restore bowel function is recommended in the National Comprehensive Cancer Network guidelines for mSBO. Yet, it is unknown how often dexamethasone is used for mSBO and whether results from nonresearch settings support its use. Methods: This is a multicenter retrospective cohort study including unique admissions for mSBO from January 1, 2019 to December 31, 2021. Dexamethasone use and management outcomes were summarized with descriptive statistics and multiple logistic regression. Results: Among 571 admissions (68% female, mean age 63 years, 85% history of abdominal surgery) that were eligible and initially nonoperative, 26% [95% confidence interval (CI) = 23%-30%] received dexamethasone treatment (69% female, mean age 62 years, 87% history of abdominal surgery). Dexamethasone use by site ranged from 13% to 52%. Among dexamethasone recipients, 13% (95% CI = 9%-20%) subsequently required nonelective surgery during the same admission and 4 dexamethasone-related safety-events were reported. Amongst 421 eligible admissions where dexamethasone was not used, 17% (95% CI = 14%-21%) required nonelective surgery. Overall, the unadjusted odds ratio (OR) for nonelective surgery with dexamethasone use compared to without its use was 0.7 (95% CI = 0.4-1.3). Using multiple logistic regression, OR after adjusting for site, age, sex, history of abdominal surgery, nasogastric tube, and Gastrografin use was 0.6 (95% CI = 0.3-1.1). Conclusion: Dexamethasone was used in about 1 in 4 eligible mSBO admissions with high variability of use between tertiary academic centers. This multicenter retrospective cohort study suggested an association between dexamethasone use and lower rates of nonelective surgery, representing a potential opportunity for quality improvement.

Surgical versus non-surgical management for patients with malignant bowel obstruction (S1316): a pragmatic comparative effectiveness trial.

BACKGROUND: Malignant small bowel obstruction has a poor prognosis and is associated with multiple related symptoms. The optimal treatment approach is often unclear. We aimed to compare surgical versus non-surgical management with the aim to determine the optimal approach for managing malignant bowel obstruction. METHODS: S1316 was a pragmatic comparative effectiveness trial done within the National Cancer Trials Network at 30 hospital and cancer research centres in the USA, Mexico, Peru, and Colombia. Participants had an intra-abdominal or retroperitoneal primary cancer confirmed via pathological report and malignant bowel disease; were aged 18 years or older with a Zubrod performance status 0-2 within 1 week before admission; had a surgical indication; and treatment equipoise. Participants were randomly assigned (1:1) to surgical or non-surgical treatment using a dynamic balancing algorithm, balancing on primary tumour type. Patients who declined consent for random assignment were offered a prospective observational patient choice pathway. The primary outcome was the number of days alive and out of the hospital (good days) at 91 days. Analyses were based on intention-to-treat linear, logistic, and Cox regression models combining data from both pathways and adjusting for potential confounders. Treatment complications were assessed in all analysed patients in the study. This completed study is registered with ClinicalTrials.gov, NCT02270450. FINDINGS: From May 11, 2015, to April 27, 2020, 221 patients were enrolled (143 [65%] were female and 78 [35%] were male). There were 199 evaluable participants: 49 in the randomised pathway (24 surgery and 25 non-surgery) and 150 in the patient choice pathway (58 surgery and 92 non-surgery). No difference was seen between surgery and non-surgery for the primary outcome of good days: mean 42·6 days (SD 32·2) in the randomised surgery group, 43·9 days (29·5) in the randomised non-surgery group, 54·8 days (27·0) in the patient choice surgery group, and 52·7 days (30·7) in the patient choice non-surgery group (adjusted mean difference 2·9 additional good days in surgical versus non-surgical treatment [95% CI -5·5 to 11·3]; p=0·50). During their initial hospital stay, six participants died, five due to cancer progression (four patients from the randomised pathway, two in each treatment group, and one from the patient choice pathway, in the surgery group) and one due to malignant bowel obstruction treatment complications (patient choice pathway, non-surgery). The most common grade 3-4 malignant bowel obstruction treatment complication was anaemia (three [6%] patients in the randomised pathway, all in the surgical group, and five [3%] patients in the patient choice pathway, four in the surgical group and one in the non-surgical group). INTERPRETATION: In our study, whether patients received a surgical or non-surgical treatment approach did not influence good days during the first 91 days after registration. These findings should inform treatment decisions for patients hospitalised with malignant bowel obstruction. FUNDING: Agency for Healthcare Research and Quality and the National Cancer Institute. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

TP53 Sequencing and p53 Immunohistochemistry Predict Outcomes When Bevacizumab Is Added to Frontline Chemotherapy in Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study.

PURPOSE: The status of p53 in a tumor can be inferred by next-generation sequencing (NGS) or by immunohistochemistry (IHC). We examined the association between p53 IHC and sequence and whether p53 IHC alone, or integrated with TP53 NGS, predicts the outcome. METHODS: From GOG-86P, a randomized phase II study of chemotherapy combined with either bevacizumab or temsirolimus in advanced endometrial cancer, 213 cases had p53 protein expression data measured by IHC and TP53 NGS data. An analysis was designed to integrate p53 expression by IHC with the presence or absence of a TP53 mutation. These variables were further correlated with progression-free survival (PFS) and overall survival (OS) in the chemotherapy plus bevacizumab arms versus the chemotherapy plus temsirolimus arm. RESULTS: In the analysis of p53 IHC, the most striking treatment effect favoring bevacizumab was in cases where p53 was overexpressed (PFS hazard ratio [HR]: 0.46, 95% CI, 0.26 to 0.88; OS HR: 0.31, 95% CI, 0.16 to 0.62). On integrated analysis, patients with TP53 missense mutations and p53 protein overexpression had a similar treatment effect on PFS (HR: 0.41, 95% CI, 0.22 to 0.83) and OS (HR: 0.28, 95% CI, 0.14 to 0.59) favoring bevacizumab plus chemotherapy relative to temsirolimus plus chemotherapy. Concordance between TP53 NGS and p53 IHC was 88%. Concordance was 92% when cases with TP53 mutations and POLE mutations or mismatch repair deficiency were removed. CONCLUSION: IHC for p53 alone or when integrated with sequencing for TP53 identifies a specific, high-risk tumor genotype/phenotype for which bevacizumab is particularly beneficial in improving outcomes when combined with chemotherapy.

Phase III Randomized Trial of Maintenance Taxanes Versus Surveillance in Women With Advanced Ovarian/Tubal/Peritoneal Cancer: A Gynecologic Oncology Group 0212:NRG Oncology Study.

PURPOSE: To compare taxane maintenance chemotherapy, paclitaxel (P) and paclitaxel poliglumex (PP), with surveillance (S) in women with ovarian, peritoneal, or fallopian tube (O/PC/FT) cancer who attained clinical complete response after first-line platinum-taxane therapy. METHODS: Women diagnosed with O/PC/FT cancer who attained clinical complete response after first-line platinum-taxane-based chemotherapy were randomly allocated 1:1:1 to S or maintenance, P 135 mg/m2 once every 28 days for 12 cycles, or PP at the same dose and schedule. Overall survival (OS) was the primary efficacy end point. RESULTS: Between March 2005 and January 2014, 1,157 individuals were enrolled. Grade 2 or worse GI adverse events were more frequent among those treated with taxane (PP: 20%, P: 27% v S: 11%). Grade 2 or worse neurologic adverse events occurred more often with taxane treatment (PP: 46%, P: 36% v S: 14%). At the fourth scheduled interim analysis, both taxane regimens passed the OS futility boundary and the Data Monitoring Committee approved an early release of results. With a median follow-up of 8.1 years, 653 deaths were reported; none were attributed to the study treatment. Median survival durations were 58.3, 56.8, and 60.0 months for S, P, and PP, respectively. Relative to S, the hazard of death for P was 1.091 (95% CI, 0.911 to 1.31; P = .343) and for PP, it was 1.033 (95% CI, 0.862 to 1.24; P = .725). The median times to first progression or death (PFS) were 13.4, 18.9, and 16.3 months for S, P, and PP, respectively. Hazard ratio = 0.801; 95% CI, 0.684 to 0.938; P = .006 for P and hazard ratio = 0.854; 95% CI, 0.729 to 1.00; P = .055 for PP. CONCLUSION: Maintenance therapy with P and PP did not improve OS among patients with newly diagnosed O/tubal/peritoneal cancer, but may modestly increase PFS. GI and neurologic toxicities were more frequent in the taxane treatment arms.

Strategic Planning and Essential Steps for Establishing a Uterine Transplant and Rehabilitation Program: From Idea to Reality.

UTx is performed to address absolute uterine infertility in the presence of uterine agenesis, a nonfunctional uterus, or after a prior hysterectomy. After the initial success of UTx resulting in a livebirth (2014) in Sweden, there are over 70 reported UTx surgeries resulting in more than 40 livebirths worldwide. Currently, UTx has been performed in over 10 countries. As UTx is transitioning from an "experimental procedure" to a clinical option, an increasing number of centers may contemplate a UTx program. This article discusses essential steps for establishment of a successful UTx program. These principles may be implemented in cis- and transgender UTx candidates.

Vaginal oligometastatic disease of colorectal primary: Report of a novel therapeutic approach.

Vaginal oligometastatic disease of colorectal primary is a rare malignancy with few reported cases in the literature and no standardized treatment paradigm. We report on the definitive management of an unusual case of an elderly woman with the aforementioned disease. A 78-year-old African-American woman presented with vaginal spotting and was found to have a vaginal lesion. Final pathology was consistent with moderately differentiated adenocarcinoma of colorectal primary. Extensive work up, which included endoscopies, pathologic analyzes, and imaging workup, did not reveal a primary gastrointestinal malignancy. The patient underwent partial vaginectomy and final pathology once again confirmed moderately differentiated adenocarcinoma of colorectal primary (CDX 2 and CEA positive, ER/PR, and CK 7 negative) with negative margins. She went on to receive adjuvant concurrent chemoradiation with 5-FU based chemotherapy. She received 45 Gy in 25 fractions to the whole pelvis followed by an HDR brachytherapy boost to 12 Gy in two fractions. Unfortunately, 10 months after completing radiation, she was found to have adenocarcinoma arising from a hepatic flexure colon polyp on colonoscopy. She required definitive surgical resection and was staged as mpT3N0M1. She received 12 cycles of 5-FU and at 2-year follow-up was found to be disease free with no evidence of locoregional recurrence or distant metastatic disease. Continued long-term follow up is warranted.

Mutated p53 portends improvement in outcomes when bevacizumab is combined with chemotherapy in advanced/recurrent endometrial cancer: An NRG Oncology study.

BACKGROUND: Successfully combining targeted agents with chemotherapy is an important future goal for cancer therapy. However, an improvement in patient outcomes requires an enhanced understanding of the tumor biomarkers that predict for drug sensitivity. NRG Oncology/Gynecologic Oncology Group (GOG) Study GOG-86P was one of the first attempts to combine targeted agents (bevacizumab or temsirolimus) with chemotherapy in patients with advanced endometrial cancer. Herein we performed exploratory analyses to examine the relationship between mutations in TP53, the most commonly mutated gene in cancer, with outcomes on GOG-86P. METHODS: TP53 mutational status was determined and correlated with progression-free survival (PFS) and overall survival (OS) on GOG-86P. RESULTS: Mutations in TP53 were associated with improved PFS and OS for patients that received bevacizumab as compared to temsirolimus (PFS: HR 0.48, 95% CI 0.31, 0.75; OS: HR: 0.61, 95% CI 0.38, 0.98). By contrast, there was no statistically significant difference in PFS or OS between arms for cases with WT TP53. CONCLUSIONS: This exploratory study suggests that combining chemotherapy with bevacizumab, but not temsirolimus, may enhance PFS and OS for patients whose tumors harbor mutant p53. These data set the stage for larger clinical studies evaluating the potential of TP53 mutational status as a biomarker to guide choice of treatment for endometrial cancer patients. Clintrials.gov: NCT00977574.

Seven decades of chemotherapy clinical trials: a pan-cancer social network analysis.

Clinical trials establish the standard of cancer care, yet the evolution and characteristics of the social dynamics between the people conducting this work remain understudied. We performed a social network analysis of authors publishing chemotherapy-based prospective trials from 1946 to 2018 to understand how social influences, including the role of gender, have influenced the growth and development of this network, which has expanded exponentially from fewer than 50 authors in 1946 to 29,197 in 2018. While 99.4% of authors were directly or indirectly connected by 2018, our results indicate a tendency to predominantly connect with others in the same or similar fields, as well as an increasing disparity in author impact and number of connections. Scale-free effects were evident, with small numbers of individuals having disproportionate impact. Women were under-represented and likelier to have lower impact, shorter productive periods (P < 0.001 for both comparisons), less centrality, and a greater proportion of co-authors in their same subspecialty. The past 30 years were characterized by a trend towards increased authorship by women, with new author parity anticipated in 2032. The network of cancer clinical trialists is best characterized as strategic or mixed-motive, with cooperative and competitive elements influencing its appearance. Network effects such as low centrality, which may limit access to high-profile individuals, likely contribute to the observed disparities.

A phase II evaluation of elesclomol sodium and weekly paclitaxel in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube or primary peritoneal cancer: An NRG oncology/gynecologic oncology group study.

OBJECTIVE: Preclinical data suggest elesclomol increases oxidative stress and enhances sensitivity to cytotoxic agents. The objective of this prospective multicenter phase 2 trial was to estimate the activity of IV elesclomol plus weekly paclitaxel in patients with platinum-resistant recurrent ovarian, tubal or peritoneal cancer through the frequency of objective tumor responses (ORR). METHODS: Patients with measurable disease, acceptable organ function, performance status ≤ 2, and one prior platinum containing regimen were eligible. A two-stage design was utilized with a target sample size of 22 and 30 subjects, respectively. Prior Gynecologic Oncology Group studies within the same population involving single agent taxanes showed an ORR of approximately (20%) and served as a historical control for direct comparison. The present study was designed to determine if the regimen had an ORR of ≥40% with 90% power. RESULTS: Fifty-eight patients were enrolled, of whom 2 received no study treatment and were inevaluable. The median number of cycles was 3 (268 total cycles, range 1-18). The number of patients responding was 11 (19.6%; 90% CI 11.4% to 30.4%) with one complete response. The median progression-free survival and overall survival was 3.6 months and 13.3 months, respectively. The median ORR duration was 9.2 months. Percentages of subjects with grade 3 toxicity included: Neutropenia 9%; anemia 5%; metabolic 5%; nausea 4%; infection 4%; neurologic (mostly neuropathy) 4%; and vascular (mostly thromboembolism) 4%. There were no grade 4 toxicities reported. CONCLUSIONS: This combination was well tolerated but is unworthy of further investigation based on the proportion responding [ClinicalTrials.gov Identifier: NCT00888615].

An Unusual Electrocardiogram.

A 56-year-old female was hospitalized and her admission ECG differed from previous tracings. Knowledge of variant cardiac anatomy along with awareness of common pitfalls in ECG recording reveals the clinical diagnosis and explains the difference.

Society of Gynecologic Oncology Clinical Outcomes Registry: From small beginnings come great things.

OBJECTIVE: Clinical registries within medical societies have demonstrated the capacity to promote quality improvement. Opportunities for well-designed data repositories could yield reliable national standards for informing reimbursement, determining adherence to care guidelines, maintaining board certification, and developing bundled payment models. Looking to the future, we set out to develop a gynecologic cancer registry serving the members of the Society of Gynecologic Oncology (SGO). METHODS: The SGO Clinical Outcomes Registry (COR) initiated a web-based data entry platform as a foray into developing a functional registry, compiling data elements specific to gynecologic oncology. Endometrial and ovarian cancer patients began enrollment in early 2014. Within one year, 19 sites were participating with the addition of cervical cancer patients in January 2015. RESULTS: To date, >6500 patients are currently entered from 29 sites, and the COR is being queried to address topics of quality improvement, disparities, and cancer outcomes. CONCLUSIONS: The SGO COR has proven the feasibility of developing a functional gynecologic cancer registry, with high uptake, rapid accrual, and ability to investigate topics of quality and outcome using the COR.

The role of neoadjuvant chemotherapy in the management of patients with advanced stage ovarian cancer: Survey results from members of the society of gynecologic oncologists, a 5-year follow-up.

•NACT use among SGO members for ovarian cancer is explored given recent trials.•Fewer SGO members feel they can't predict optimal cytoreduction pre-operatively.•Laparoscopy use has increased both for diagnosis and treatment of ovarian cancer.•Very high optimal cytoreduction rates are reported from SGO members.•Despite recent studies, SGO members don't regularly treat patients with NACT/ID.

Evaluation of Pulmonary Complications in Robotic-Assisted Gynecologic Surgery.

STUDY OBJECTIVE: To conduct a study to assess the incidence of pulmonary complications associated with robotic-assisted surgeries in women with various gynecologic conditions. DESIGN: Retrospective study. SETTING: Tertiary care center. PATIENTS: There were 296 patients included in this study. Patient characteristics and comorbidities were noted. Surgical characteristics and respiratory parameters were recorded for all patients. Intraoperative complications and postoperative complications were noted for up to 30 days after surgery. Patients were followed for a median of 231 days in an effort to detect any long-term complications. The primary outcome was postoperative pulmonary complications, and the secondary outcome measure was all complications. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study was composed of 296 patients. Only 5 patients (2%) experienced a pulmonary complication. Overall, 38 patients (13%) experienced complications, including both major and minor complications. Average airway pressure and maximum airway pressure were both associated with a significantly higher risk of pulmonary complications (p = .02 and p = .008, respectively). Age, body mass index, tidal volume, respiratory rate, estimated blood loss, and length of procedure were all found to not be statistically significant in patients who experienced a pulmonary complication versus patients who did not experience one. CONCLUSION: Robotic gynecologic surgery is safe and tolerated well by most patients. This study supports that there is a low rate of pulmonary complications in those who undergo robotic-assisted surgery for gynecologic indications, as well as a low overall complication rate.

Reducing Overtreatment in Gynecologic Oncology: The Case for Less in Endometrial and Ovarian Cancer.

A growing awareness of the harms of overtreatment in cancer care has reached physicians, patients, health policy makers, and medical researchers. Overtreatment exposes patients to the risk of adverse events from procedures or medications that were not necessary. This review examines common practices in gynecologic malignancies that are unlikely to produce direct benefit to patients with these malignancies, but are likely to produce harms. Specifically, we will explore the utility of lymphadenectomy and adjuvant radiation for women with early-stage endometrial cancer; and screening for recurrence and continuous chemotherapy for advanced-stage ovarian cancer patients.

A Delay from Diagnosis to Treatment Is Associated with a Decreased Overall Survival for Patients with Endometrial Cancer.

OBJECTIVES: While Caucasian women are more likely to be diagnosed with endometrial cancer compared to African-American women, the rate of mortality is higher for African Americans. The cause of this disparity is unknown. We analyzed the time interval from diagnosis of endometrial cancer to treatment as it pertains to race and socioeconomic factors and its possible impact on survival. METHODS: This was a retrospective, single institution chart review using a cancer registry database. We identified 889 patients who were diagnosed with endometrial cancer between January 2005 and June 2012. Clinicopathologic characteristics, demographics, insurance status, distance from medical center, body mass index (BMI), dates of diagnosis, and treatment were obtained from the medical records. Survival and association was determined by a one-way ANOVA test. RESULTS: At the time of the study, 699 patients were alive and 190 dead. The average age was noted to be 62 years (24-91 years). Stages I-IV disease accounted for 69, 6, 15, and 10%, respectively. White race accounted for 64%, African Americans 24%, and Hispanics 7% of our study population. Majority of patients were privately insured (n = 441) followed by Medicare (n = 375). The mean interval time from diagnosis to treatment was 47.5 days (0-363). A statistically significant difference was noted for this time interval with regard to both race and insurance status: white and African Americans (42.6 vs. 57.3 days, p = 0.048), privately insured and Medicare (38.4 vs. 54.1 days, p < 0.001). There was a significant association with increased risk of death with a longer delay (43.3 vs. 64.8 days, p < 0.001). No statistically significance was noted for distance from medical center or BMI. CONCLUSION: A significant increase in interval of time from diagnosis to treatment of endometrial cancer was seen in both race and insurance status. A longer interval from diagnosis to treatment was associated mortality. The causes of these delays are likely multifactorial but deem further investigation given these data.