Delayed publication of clinical trials in gynecologic oncology.

OBJECTIVES: Delays in clinical trial publication can hinder timely implementation of evidence-based practices. We sought to determine publication rates and time to publication for clinical trials addressing gynecologic malignancies. METHODS: All clinical trials addressing gynecologic cancers in the ClinicalTrials.gov registry with a primary completion date between 1/1/2018 and 1/1/2020 were identified. The primary outcome was publication rate. All included studies had been completed for at least 3 years. Secondary outcomes were time to publication and associations between publication rate and sponsor, cancer type, and the number and location of primary study sites. RESULTS: Of the 290 trials included, 161 (55.5%) had a peer-reviewed publication for the primary outcome within at least 3 years after completion. Of these, 123 had positive results (76.4%) and 38 were negative (23.6%). The average duration from primary completion to manuscript publication was 23.6 months (SD 13.9; median 21.4, IQR 15.1-32.4). Only 73 had results posted on the ClinicalTrials.gov registry (25.2%). Studies with positive findings had a significantly faster time to publication than those with negative results (22.0 mo vs 29.0 mo, p = 0.009). There was no significant difference between publication rate and funding source, cancer type, or location and number of primary sites. CONCLUSIONS: Timely publication of clinical trials addressing gynecologic cancers remains an issue. Studies with positive findings were published faster than those with negative results, but the average publication time was still almost 2 years from trial completion. Further efforts should be made to identify and address barriers to clinical trial publication.

Predictors of Breastfeeding among Patients Admitted with Preterm Prelabor Rupture of Membranes.

OBJECTIVE: We sought to describe rates of breastmilk feeding (BF) at hospital discharge and 6 weeks postpartum and to identify risk factors for noninitiation or cessation among pregnancies complicated by preterm prelabor rupture of membranes (PPROM). STUDY DESIGN: Retrospective cohort study of pregnant persons with PPROM admitted to a single tertiary center (2013-2019). Patients with deliveries complicated by intrauterine or neonatal demise or with incomplete BF data were excluded. Demographic, antepartum, and delivery characteristics were evaluated. Primary analysis identified rate of BF initiation at maternal discharge and factors associated with noninitiation. Secondary analysis evaluated BF continuation and factors associated with cessation at 6 weeks postpartum. Bivariate statistics were used to compare characteristics and logistic regression was used to estimate adjusted odds ratios (aOR). RESULTS: Of 397 patients with PPROM, 342(86%) initiated BF prior to discharge. Those reporting tobacco use in pregnancy were less likely to initiate BF (aOR: 0.32; 95% confidence interval [CI]: 0.16, 0.64). In contrast, private insurance (aOR: 2.53; 95% CI: 1.19, 5.37) and pregnancy latency ≥ 14 days (aOR: 3.02; 95% CI: 1.09, 8.38) were associated with BF initiation at hospital discharge. Of the 293 patients with postpartum follow-up, only 214 (73%) had BF continuation at 6 weeks postpartum. Maternal age <20 years (aOR: 0.07; 95% CI: 0.01, 0.68) and multiparity (aOR: 0.54; 95% CI: 0.29, 0.99) were associated with BF cessation. Patients with private insurance were observed to have increased odds of BF continuation (aOR: 2.10; 95% CI: 1.07, 4.12). CONCLUSION: Among patients with PPROM, tobacco use may be associated with noninitiation of BF prior to discharge, whereas age < 20 years and multiparity were associated with cessation by 6 weeks postpartum. Longer pregnancy latency ≥ 14 days was associated with BF initiation prior to discharge. Private insurance was associated with increased rates of BF initiation and continuation postpartum. BF education and support should be offered to all patients admitted for PPROM. KEY POINTS: · Tobacco use may be associated with BF noninitiation.. · Young age and multiparity are linked with BF cessation.. · Private insurance resulted in BF initiation and continuation..

Risk Factors for Adverse Maternal Outcomes following Expectantly Managed Preterm Prelabor Rupture of Membranes.

OBJECTIVE: We sought to characterize the incidence and risk factors associated with developing maternal morbidity following preterm prelabor rupture of membranes. STUDY DESIGN: Retrospective case-control study of patients with preterm prelabor rupture of membranes at a single institution from 2013 to 2019 admitted at ≥23 weeks gestational age. The primary outcome was a composite of maternal morbidity which included: death, sepsis, intensive care unit (ICU) admission, acute kidney injury, postpartum dilation and curettage, postpartum hysterectomy, venous thromboembolism, postpartum hemorrhage, postpartum wound complication, postpartum endometritis, pelvic abscess, postpartum pneumonia, readmission, and/or need for blood transfusion were compared with patients without above morbidities. Severe morbidity was defined as: death, ICU admission, venous thromboembolism, acute kidney injury, postpartum hysterectomy, sepsis, and/or transfusion >2 units. Demographics, antenatal, and delivery characteristics were compared between patients with and without maternal morbidity. Bivariate statistics and regression models were used to compare outcomes and calculate adjusted odd ratios. RESULTS: Of 361 included patients, 64 patients (17.7%) experienced maternal morbidity and nine (2.5%) had severe morbidity. Patients who experienced maternal morbidity were significantly (p < 0.05) more likely to be older, have private insurance, have BMI ≥40, have chorioamnionitis at delivery, and undergo cesarean or operative vaginal delivery when compared with patients who did not experience morbidity. After controlling for confounders, cesarean delivery (aOR 2.38, 95% CI[1.30,4.39]), body mass index ≥40 at admission (aOR 2.54, 95% CI[1.12,5.79]), private insurance (aOR 3.08, 95% CI[1.54,6.16]), and tobacco use (aOR 3.43, 95% CI[1.58,7.48]) were associated with increased odds of maternal morbidity. CONCLUSION: In this cohort, maternal morbidity occurred in 17.7% of patients with preterm prelabor rupture of membranes. Private insurance, body mass index ≥40, tobacco use, and cesarean delivery were associated with higher odds of morbidity. These data can be used in counseling and to advocate for smoking cessation. KEY POINTS: · 17.7% of patients with PPROM experienced maternal morbidity.. · BMI ≥40 was associated with higher odds of maternal morbidity.. · Tobacco use and cesarean delivery were associated with higher odds of maternal morbidity..

Estimating the Impact of Extended Delay to Surgery for Stage I Non-small-cell Lung Cancer on Survival.

OBJECTIVE: The purpose of this study is to evaluate the impact of extended delay to surgery for stage I NSCLC. SUMMARY OF BACKGROUND DATA: During the COVID-19 pandemic, patients with NSCLC may experience delays in care, and some national guidelines recommend delays in surgery by >3 months for early NSCLC. METHODS: Using data from the National Lung Screening Trial, a multi-center randomized trial, and the National Cancer Data Base, a multi-institutional oncology registry, the impact of "early" versus "delayed" surgery (surgery received 0-30 vs 90-120 days after diagnosis) for stage I lung adenocarcinoma and squamous cell carcinoma (SCC) was assessed using multivariable Cox regression analysis with penalized smoothing spline functions and propensity score-matched analyses. RESULTS: In Cox regression analysis of the National Lung Screening Trial (n = 452) and National Cancer Data Base (n = 80,086) cohorts, an increase in the hazard ratio was seen the longer surgery was delayed. In propensity score-matched analysis, no significant differences in survival were found between early and delayed surgery for stage IA1 adenocarcinoma and IA1-IA3 SCC (all P > 0.13). For stage IA2-IB adenocarcinoma and IB SCC, delayed surgery was associated with worse survival (all P < 0.004). CONCLUSIONS: The mortality risk associated with an extended delay to surgery differs across patient subgroups, and difficult decisions to delay care during the COVID-19 pandemic should take substage and histologic subtype into consideration.

Stereotactic Body Radiotherapy Versus Delayed Surgery for Early-stage Non-small-cell Lung Cancer.

OBJECTIVE: To evaluate the overall survival of patients with operable stage IA non-small-cell lung cancer (NSCLC) who undergo "early" SBRT (within 0-30 days after diagnosis) versus "delayed" surgery (90-120 days after diagnosis). SUMMARY OF BACKGROUND DATA: During the COVID-19 pandemic, national guidelines have recommended patients with operable stage IA NSCLC to consider delaying surgery by at least 3 months or, alternatively, to undergo SBRT without delay. It is unknown which strategy is associated with better short- and long-term outcomes. METHODS: Multivariable Cox proportional hazards modeling and propensity score-matched analysis was used to compare the overall survival of patients with stage IA NSCLC in the National Cancer Data Base from 2004 to 2015 who underwent "early" SBRT (0-30 days after diagnosis) versus that of patients who underwent "delayed" wedge resection (90-120 days after diagnosis). RESULTS: During the study period, 570 (55%) patients underwent early SBRT and 475 (45%) underwent delayed wedge resection. In multivariable analysis, delayed resection was associated with improved survival [adjusted hazard ratio 0.61; (95% confidence interval (CI): 0.50-0.76)]. Propensity-score matching was used to create 2 groups of 279 patients each who received early SBRT or delayed resection that were well-matched with regard to baseline characteristics. The 5-year survival associated with delayed resection was 53% (95% CI: 45%-61%) which was better than the 5-year survival associated with early SBRT (31% [95% CI: 24%-37%]). CONCLUSION: In this national analysis, for patients with stage IA NSCLC, extended delay of surgery was associated with improved survival when compared to early treatment with SBRT.

Morbidity of late-season influenza during pregnancy.

BACKGROUND: In the Northern Hemisphere, influenza season typically starts in December and lasts through March. Pregnant people are at increased risk for influenza-related morbidity and mortality. Potentially, new viral strains or reduced provider suspicion leading to delayed diagnosis of late-season influenza could result in an increased risk of severe infection. OBJECTIVE: This study aimed to assess the incidence and morbidity associated with late-season influenza in pregnancy, compared with influenza in other seasons. STUDY DESIGN: This was a retrospective cohort study using the 2007-2018 National Inpatient Sample. Pregnant patients with discharge diagnosis codes consistent with influenza infection were compared on the basis of hospital admission quarter (quarter 1: October to December; quarter 2: January to March; quarter 3: April to June; quarter 4: July to September), with quarter 3 defined as "late-season." The primary outcome was the severe maternal morbidity composite defined by the Centers for Disease Control and Prevention. The secondary outcomes included sepsis, shock, acute renal failure, acute heart failure, temporary tracheostomy, and invasive mechanical ventilation. Associations between outcomes and quarter of infection were adjusted for age, hospitalization type (antepartum, delivery, or postpartum), and comorbid conditions using relative risk regression, weighted to reflect the National Inpatient Sample design. RESULTS: Of 7355 hospitalizations, corresponding to a weighted national estimate of 36,042, 2266 (30.8%) occurred in quarter 1, 4051 (55.0%) in quarter 2, 633 (8.6%) in quarter 3, and 405 (5.5%) in quarter 4. A nonsignificant trend toward higher rates of severe maternal morbidity was seen in the "late-season" compared with other quarters (13.9% [quarter 3] vs 10.5% [quarter 1] vs 12.1% [quarter 2] vs 13.6% [quarter 4]; P=.07). Moreover, sepsis was more common in patients with late-season influenza (8.0% [quarter 3] vs 4.8% [quarter 1] vs 5.8% [quarter 2] vs 5.9% [quarter 4]; P=.03). In the adjusted analyses, patients with late-season influenza had a 1.34 (95% confidence interval, 1.01-1.78) higher risk of severe maternal morbidity and 1.57 (95% confidence interval, 1.06-2.32) higher risk of sepsis than patients with influenza in quarter 1. CONCLUSION: Influenza infection between April and June, that is, late-season influenza, is associated with a higher risk of severe maternal morbidity and sepsis in pregnant patients. Obstetrical providers must continue to have awareness and suspicion for influenza infection during these months.

Gestational weight gain and patterns of breastfeeding among patients with class III obesity.

BACKGROUND: Maternal obesity is associated with delayed lactogenesis and shorter duration of breastfeeding compared to patients with a normal BMI. RESEARCH AIM/QUESTION: We investigated the impact of excessive gestational weight gain, defined as greater than the Institute of Medicine guidelines (>9.1 kg), on the initiation and duration of breastfeeding in patients with class III obesity. METHODS: Retrospective cohort of patients with body mass index ≥40 in first trimester, delivering a singleton term infant at a tertiary care center between July 2013 and December 2017. Primary outcome was exclusive breastfeeding at discharge and at postpartum visit. Secondary outcomes included any breastfeeding at discharge and postpartum visit, and cessation of breastfeeding by the postpartum visit. Descriptive statistics were used to compare those whose gestational weight gain exceeded (eIOM) versus met (mIOM) Institute of Medicine guidelines. Regression models were performed to adjust for baseline confounding factors. RESULTS: Of 294 women included, 117(39.8%) were in the eIOM group. These women were more likely to be primigravida, have a higher delivery BMI, greater delivery blood loss, and have a neonate admitted to the intensive care unit. Exclusive breastfeeding at discharge was not different between eIOM and mIOM (66.7% vs 70.9%, p = .44), nor did eIOM impact likelihood of exclusive breastfeeding at postpartum visit (40.1% vs 34.2%, p = .31). When controlling for confounding factors, breastfeeding at discharge (aOR 1.54 95% CI [0.68-3.49]) or postpartum visit (aOR 0.67[0.31-1.47]) did not differ between eIOM compared to mIOM. CONCLUSIONS: Among women with class III obesity, excessive gestational weight gain did not impact the rate of exclusive breastfeeding at discharge or postpartum visit.

Perioperative Outcomes and Survival After Preoperative Immunotherapy for Non-Small Cell Lung Cancer.

BACKGROUND: Although preoperative immunotherapy is increasingly utilized for non-small cell lung cancer, there remains a paucity of robust clinical data on its safety and long-term survival. Our objective was to evaluate the perioperative outcomes and survival associated with immunotherapy followed by surgery for patients with non-small cell lung cancer. METHODS: Outcomes of patients with non-small cell lung cancer who underwent lung resection after preoperative chemotherapy with or without radiation or immunotherapy (with or without chemotherapy or chemoradiation) in the National Cancer Database (2010 to 2017) were evaluated using Kaplan-Meier analysis, multivariable logistic regression, multivariable Cox proportional hazards analysis, and propensity score-matched analysis. RESULTS: From 2010 to 2017, 236 patients (2.2%) received immunotherapy and 10 715 patients received preoperative chemotherapy followed by surgery. There were no significant differences between the immunotherapy and preoperative chemotherapy groups with regard to margin positivity (8.5% [n = 20] vs 7.5% [n = 715], P = .98), 30-day readmission (4.2% [n = 10] vs 4.1% [n = 440], P = .87), and 30-day mortality (0.4% [n = 1] vs 2.4% [n = 253], P = .25). The immunotherapy and preoperative chemotherapy groups had similar overall survival (5-year survival 63% [95% confidence interval, 50% to 74%] vs 51% [95% confidence interval, 50% to 52%], log rank P = .06; multivariable adjusted hazard ratio 0.98; 95% confidence interval, 0.67 to 1.41; P = .90). A propensity score matched analysis of 344 patients, well matched by preoperative characteristics, showed no significant differences in short-term outcomes and overall survival (log rank P = 1.00) between the two groups. CONCLUSIONS: In this national analysis, preoperative immunotherapy followed by surgery for non-small cell lung cancer was found to be safe and feasible with similar short-term outcomes and overall survival when compared with preoperative chemotherapy followed by surgery.

Perioperative Outcomes and 5-year Survival After Open versus Thoracoscopic Sleeve Resection for Lung Cancer.

The objective of this study was to evaluate the impact of a video-assisted thoracoscopic (VATS) approach on outcomes in patients who underwent sleeve lobectomy for non-small-cell lung cancer (NSCLC). Outcomes of patients with cT1-T3, N0-N2, M0 NSCLC who underwent sleeve lobectomy in the National Cancer Data Base (NCDB) from 2010-2015 were assessed using Kaplan-Meier, propensity score-matching, and Cox proportional hazards analyses. An "intent-to-treat" analysis was performed. In the NCDB, 210 sleeve lobectomy patients met inclusion criteria (VATS 44 [21%], thoracotomy 166 [79%]). Nine (20%) of the VATS cases were converted to open. Compared to an open approach, VATS was associated with no significant differences in lymph nodes examined (median 9.5 vs 9.0; p = 0.72), length of stay (median 6 days vs 6 days; p = 0.36), 30-day mortality (4.5% vs 1.8%; p = 0.28), and 90-day mortality (6.8% vs 4.8%; p = 0.70). There were no significant differences in 5-year survival between the VATS and open groups in both the entire cohort (VATS [85%] vs open [79%]; log-rank p = 0.91) and in a propensity score-matched analysis of 86 patients (log-rank p = 0.75). Furthermore, a VATS approach was also not associated with worse survival in multivariable analysis (HR = 0.64; 95% CI [0.23-1.78]; p = 0.39). In this national analysis, a VATS approach for sleeve lobectomy for NSCLC was not associated with worse short-term or long-term outcomes when compared to an open approach.

Impact of Surveillance After Lobectomy for Lung Cancer on Disease Detection and Survival.

INTRODUCTION: Existing guidelines for surveillance after non-small-cell lung cancer (NSCLC) treatment are inconsistent and have relatively sparse supporting literature. This study characterizes detection rates of metachronous and recurrent disease during surveillance with computed tomography scans after definitive treatment of early stage NSCLC. MATERIALS AND METHODS: The incidence of metachronous and recurrent disease in patients who previously underwent complete resection via lobectomy for stage IA NSCLC at a single center from 1996 to 2010 were evaluated. A subgroup analysis was used to compare survival of patients whose initial surveillance scan was 6 ± 3 months (early) versus 12 ± 3 months (late) after lobectomy. RESULTS: Of 294 eligible patients, 49 (17%) developed recurrent disease (14 local only, 35 distant), and 45 (15%) developed new NSCLC. Recurrent disease was found at a mean of 22 ± 19 months, and new primaries were found at a mean of 52 ± 31 months after lobectomy (P < .01). Five-year survival after diagnosis of recurrent disease was significantly lower than after diagnosis of second primaries (2.3% vs. 57.5%; P < .001). In the subgroup analysis of 187 patients, both disease detection on the initial scan (2% [2/94] vs. 4% [4/93]; P = .44) and 5-year survival (early, 80.8% vs. late, 86.7%; P = .61) were not significantly different between the early (n = 94) and the late (n = 93) groups. CONCLUSION: Surveillance after lobectomy for stage IA NSCLC is useful for identifying both new primary as well as recurrent disease, but waiting to start surveillance until 12 ± 3 months after surgery is unlikely to miss clinically important findings.