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Objectives Low-grade serous ovarian cancer (LGSC) is a relatively chemo-resistant disease with limited effective treatment options for patients with recurrence. Secondary cytoreductive surgery (SCS) is commonly offered at recurrence, although any benefit this has on survival is not fully determined. This review evaluates the impact of SCS, including residual disease, on progression-free survival (PFS) and overall survival (OS) in recurrent LGSC. Methods A comprehensive search of Medline ALL, Embase Classic + Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science was conducted to obtain studies evaluating optimal or complete SCS versus suboptimal SCS and the amount of residual disease in recurrent LGSC. Meta-analysis was performed and PFS and OS outcomes were calculated. Results 1Of 5296 studies screened, 350 progressed to full-text review, with 9 ultimately selected for inclusion in the systematic review. Two studies met criteria for meta-analysis of PFS and of OS. The presence of visible residual disease at the conclusion of SCS negatively impacted PFS (HR = 3.51, 95% CI = 1.72-7.14), whereas SCS with no residual disease significantly improved OS (HR = 0.4, 95% CI = 0.23-0.7) in patients with recurrent LGSC. Diffuse and extensive disease distribution was inversely linked to survival. In addition, SCS as an initial treatment for recurrent LGSC was associated with superior survival in comparison to chemotherapy. A short platinum-free interval was not associated with worse survival in this cohort. Conclusions Complete SCS, and to a lesser extent optimal SCS, are associated with improved PFS and OS in patients with recurrent LGSC. SCS may be a better initial treatment strategy than systemic chemotherapy for recurrent disease. Patients with recurrent LGSC should be evaluated for the role of SCS based on disease distribution and functional status, irrespective of the platinum-free interval. Prospective studies are needed to further study the role of SCS in patients with recurrent LGSC.

Objective Low-grade serous ovarian cancer (LGSOC) is a rare form of ovarian cancer that accounts for 5–10% of epithelial ovarian cancers. LGSOCs are difficult to treat as they respond poorly to traditional chemotherapy treatments. This systematic review aims to appraise the literature describing the efficacy of hormone maintenance therapy (HMT) in patients with LGSOC given after cytoreductive surgery. Methods Medline, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews were searched from inception to November 2020. No language restrictions were applied. Publications describing HMT in the primary setting following cytoreductive surgery with or without chemotherapy in women with LGSOC were included. Publications describing HMT in recurrence, non-LGSOC carcinomas, and in-vitro or animal studies were excluded along with case reports, case series, and conference proceedings. We summarized oncologic outcomes, HMT used, and hormone receptor status where reported. Studies were assessed for risk of bias and quality of evidence. Results The literature search identified 14,799 records. Four cohort studies met eligibility criteria. A total of 558 patients were included, of which 127 were treated with HMT. There was significant heterogeneity between studies demonstrated by differences in HMT regimens used, dosing, and study population, leading to various outcomes following treatment with HMT. Conclusions Treatment of LGSOC remains a challenge. One retrospective study demonstrated improved progression-free survival following HMT for LGSOC, while two others failed to show significant improvements. However, there is limited data available in the literature which restricts the generalizability of these results. Therefore, well-designed, prospective, and randomized trials are needed to confirm the benefit of HMT in patients with this rare subgroup of ovarian cancer.

Background Systemic inflammatory response (SIR) may influence prognosis in epidermal growth factor receptor (EGFR)-mutated (m) non–small-cell lung cancer (NSCLC). Pretreatment SIR markers (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio [LMR], lactate dehydrogenase [LDH], and lung immune prognostic index [LIPI]) were assessed as prognostic factors in NSCLC survival. Patients and Methods Retrospective survival analysis (overall survival [OS] and progression-free survival [PFS]) of EGFR-mutated NSCLC patients at Princess Margaret Cancer Centre were performed separately for early (I-IIIa) and late (IIIb-IV) stage disease for individual SIR variables, dichotomized by optimal cutoff points by Kaplan-Meier survival analysis and multivariable Cox proportional hazard modeling. A systematic review and meta-analysis of known SIR studies in patients with late-stage EGFR-mutated were also performed. Results From 2012 to 2019, in 530 patients, significant adjusted hazard ratios (aHR) for OS comparing high versus low NLR were 2.12 for early stage and 1.79 for late stage disease. Additionally, late stage cohorts had significant associations, as follows: high versus low derived NLR, aHR = 1.53; LMR, aHR = 0.62; LDH, aHR = 2.04; and LIPI, aHR = 2.04. Similar patterns were found for PFS in early stage NLR (aHR = 1.96) and late stage NLR (aHR = 1.46), while for PFS, only late stage derived NLR (aHR = 1.34), LDH (aHR = 1.75), and LIPI (aHR = 1.66) were significant. A meta-analysis confirmed that NLR, LMR, LDH, and LIPI were all significantly associated with OS and PFS in the late stage. Conclusion This primary study and meta-analysis demonstrated that LMR and LDH were significantly associated with late stage EGFR-mutated NSCLC outcomes, and the LIPI scoring system was prognostic. NLR remained an independent prognostic factor across all stages and could represent an early marker of immuno-oncology interactions.

Background There are limited data regarding the quality of patient‐reported outcome (PRO) data in immune checkpoint inhibitor (ICI) clinical trial publications. Methods A systematic search of citations from various databases was conducted to identify prospective clinical trials involving ICI in advanced tumors from 2003 to 2020. A 30‐point score was adapted from the CONSORT PRO extension statement to assess adherence to CONSORT PRO reporting. Linear regression was used to identify factors associated with quality reporting. Results After the review of 8058 articles, 33 trials were included with ICIs as either monotherapy (91%) or part of a combination regimen (9%). The median score was 23.5 points (range 15–29). In the majority of cases (82%), PROs were reported in a separate publication from the original study. Most of the trials were conducted in the metastatic setting and predominantly in melanoma, lung, and renal cell carcinoma (RCC) (73%). Univariate analysis revealed that trials with greater than 250 patients were associated with a higher score. The score was more likely to be lower in disease sites other than melanoma, lung, and RCC and was higher in the KEYNOTE than in the CHECKMATE trial series. There was no significant correlation between the score and whether a trial met its primary end‐point or if the trial improved or worsened the quality of life. In the multivariate analysis, the number of patients enrolled to the trial, disease site, and trial series remained significant. Conclusions The quality of reporting of PROs in ICI phase II and III clinical trials is heterogeneous across various cancer sites. As PRO data are increasingly used to counsel patients and complement clinical decision making, innovative and collaborative efforts are required to improve the reporting of these essential data., There are limited data regarding the quality of patient‐reported outcome data in immune checkpoint inhibitor clinical trial publications. A systematic review was conducted of published clinical trials to assess the quality of reporting.

Background:Screening for problematic opioid use is increasingly recommended in patients receiving palliative care.Aim:To identify tools used to assess for the presence or risk of problematic opioid use in palliative care.Design:Scoping review.Data sources:Bibliographic databases (inception to January 31, 2020), reference lists, and grey literature were searched to find primary studies reporting on adults receiving palliative care and prescription opioids to manage symptoms from advanced cancer, neurodegenerative diseases, or end-stage organ diseases; and included tools to assess for problematic opioid use. There were no restrictions based on study design, location, or language.Results:We identified 42 observational studies (total 14,431 participants) published between 2009 and 2020 that used questionnaires ( n = 32) and urine drug tests ( n = 21) to assess for problematic opioid use in palliative care, primarily in US ( n = 38) and outpatient palliative care settings ( n = 36). The questionnaires were Cut down, Annoyed, Guilty, and Eye-opener (CAGE, n = 8), CAGE-Adapted to Include Drugs (CAGE-AID, n = 6), Opioid Risk Tool ( n = 9), Screener and Opioid Assessment for Patients with Pain (SOAPP; n = 3), SOAPP-Revised ( n = 2), and SOAPP-Short Form ( n = 5). Only two studies’ primary objectives were to evaluate a questionnaire’s psychometric properties in patients receiving palliative care. There was wide variation in how urine drug tests were incorporated into palliative care; frequency of abnormal urine drug test results ranged from 8.6% to 70%.Conclusion:Given the dearth of studies using tools developed or validated specifically for patients receiving palliative care, further research is needed to inform clinical practice and policy regarding problematic opioid use in palliative care.

Objectives The optimal systemic therapy strategy for advanced epithelial ovarian cancer (EOC) remains unclear. We performed a systematic review and meta-analysis to assess oncologic outcomes and toxicity of bevacizumab combination treatment in advanced EOC. Methods We conducted an electronic search of all phase 2 and 3 clinical trials involving bevacizumab combination therapy in advanced-stage EOC between 2010 and March 2020, using Embase, Medline, Epub Ahead of Print, Cochrane for clinical trials, Cochrane Database of Systematic Reviews, Web of Science and clinicaltrials.gov databases. Progression-free survival (PFS), overall survival (OS), and their hazard ratios (HR) when available were extracted. Pooled HR were calculated for each efficacy endpoint in the meta-analysis using inverse variance weighted method. Bias was assessed using the Cochrane Collaboration Risk of Bias I (ROB1) tool for randomized controlled trials. Results Thirty-five studies were included in the qualitative analysis and eight studies in the quantitative synthesis. In the first-line setting, bevacizumab combined with chemotherapy revealed a significant improvement in PFS (pooled HR = 0.72, 95% CI 0.65–0.81) when compared to chemotherapy alone but no significant OS benefit (pooled HR = 0.88, 95% CI 0.72–1.06). In the recurrent setting, bevacizumab combinations showed significant PFS (pooled HR = 0.52, 95% CI 0.47–0.58) and OS benefits (pooled HR = 0.88, 95% CI 0.79–0.99) compared with non-bevacizumab regimens. Rate of bowel perforation was low at 1.24% (range 0–4.2%). Conclusions Bevacizumab-containing regimens are associated with significant PFS benefit in advanced and recurrent epithelial ovarian cancer. While the difference in OS did not reach statistical significance in the first-line setting, bevacizumab was associated with improved survival in the recurrent setting.

Serious concerns regarding quality of conduct and reporting of noninferiority trials (NITs) have been raised. Systematic analysis of the quality of the surgical NITs is lacking. Assessing the quality of conduct, reporting, and interpretation of surgical NITs in cancer patients is critical given their potential clinical impact. We aim to assess the quality of conduct, reporting, and interpretation of NITs that investigate the effects of surgical management in cancer patients. A cross-sectional analysis of papers identified through a comprehensive literature database search was performed. Forty papers employing a phase III noninferiority (NI) randomized trial design to study effects of surgical methodology or sequencing of surgery in patients with solid cancers were included. Papers were assessed for type of analysis, justification of the noninferiority margin (NIM), consistency of type I error with confidence intervals (CIs), ability to achieve the predefined sample size, and interpretations regarding NI. Only half of the papers used both intention-to-treat and per protocol analyses; 62.5% provided no or poor justification for the NIM; 42.5% showed inconsistency of the type I error rate with CIs; 52.5% were deemed poor or fair quality, and 60.0% did not achieve the predefined sample size. One-fifth of the papers provided interpretation of the NI hypothesis that was not in concordance with the CONSORT guidelines. The quality of conduct, reporting, and interpretation of surgical NITs is suboptimal, requiring further improvements through adherence to guidelines and rigorous assessment at the stages of the study approval, funding, and the peer-review process.

Supplemental Digital Content is available in the text., Purpose The aim of this scoping review is to understand the motivations for the creation of global medical curricula, summarize methods that have been used to create these curricula, and understand the perceived premises for the creation of these curricula. Method In 2018, the authors used a comprehensive search strategy to identify papers on existing efforts to create global medical curricula published from 1998 to March 29, 2018, in the following databases: MEDLINE; MEDLINE Epub Ahead of Print, In-Process, and Other Non-Indexed Citations; Embase; Cochrane Central Register of Controlled Trials; Cochrane Database of Systematic Reviews; PsycINFO; CINAHL; ERIC; Scopus; African Index Medicus; and LILACS. There were no language restrictions. Two independent researchers applied the inclusion and exclusion criteria. Demographic data were abstracted from publications and summarized. The stated purposes, methods used for the development, stated motivations, and reported challenges of curricula were coded. Results Of the 18,684 publications initially identified, 137 met inclusion criteria. The most common stated purposes for creating curricula were to define speciality-specific standards (50, 30%), to harmonize training standards (38, 23%), and to improve the quality or safety of training (31, 19%). The most common challenges were intercountry variation (including differences in health care systems, the operationalization of medical training, and sociocultural differences; 27, 20%), curricular implementation (20, 15%), and the need for a multistakeholder approach (6, 4%). Most curricula were developed by a social group (e.g., committee; 30, 45%) or Delphi or modified Delphi process (22, 33%). Conclusions The challenges of intercountry variation, the need for a multistakeholder approach, and curricular implementation need to be considered if concerns about curricular relevance are to be addressed. These challenges undoubtedly impact the uptake of global medical curricula and can only be addressed by explicit efforts to make curricula applicable to the realities of diverse health care settings.

Background: The addition of platinum agents to anthracycline and taxane-based chemotherapy in early-stage triple negative breast cancer (TNBC) patients improves pathological complete response (pCR). Long-term outcomes, such as disease-free survival (DFS) and overall survival (OS), have not been well-established. Methods: A systematic literature review identified studies using platinum-based treatment in TNBC patients in the neoadjuvant or adjuvant setting with reportable long-term outcomes. Hazard ratios (HR) from collected data were pooled in a meta-analysis using generic inverse-variance and random effects modeling. Subgroup analyses were conducted based on treatment setting (neoadjuvant vs. adjuvant) and study design (retrospective vs. randomized controlled trials). When available, odds ratios (OR) for commonly reported safety and tolerability measures such as treatment-related death, treatment discontinuation without progression, dose reduction, neuropathy, renal impairment and hematological toxicity were calculated. Results: Seven studies comprising 1699 patients met the inclusion criteria. Median follow up was 54.5 months. All studies reported DFS and 4 studies reported OS. DFS was significantly better in platinum-based treatment (HR 0.71, 95% confidence interval (CI) 0.53-0.96; P = 0.03). However, OS was no different with a higher number of events in the platinum-based treatment arm (HR 1.17, 95% CI 0.81-1.69; P = 0.42). There was no significant difference between treatment settings (p = 0.74) or between study designs (p = 0.74), although a higher HR for OS was observed for studies in the adjuvant (HR 1.34, 95% CI 0.54-3.35) compared to neoadjuvant setting (HR 1.14, 95% CI 0.76-1.70). The reporting of toxicity was suboptimal with most studies not reporting safety and tolerability metrics clearly. Platinum-based treatment was associated with more neutropenia and thrombocytopenia and treatment discontinuation, however, the magnitude of this effect could not be estimated accurately. Conclusions: Platinum-based treatment improves DFS but has no effect on OS and increases toxicity. The discordant effect of platinum-based treatment on DFS and OS suggest the potential development of platinum resistance and worse outcomes after recurrence. The higher magnitude of discordance in adjuvant compared to neoadjuvant studies suggests an effect of platinum-based therapy on loco-regional control prior to surgery rather than prevention of distant metastatic disease. Platinum-based chemotherapy cannot be recommended in unselected patients with TNBC. Citation Format: Ramy Saleh, Michelle B Nadler, Alexandra Desnoyers, Rouhi Fazelzad, Eitan Amir. Platinum-based chemotherapy in early-stage triple negative breast cancer: A meta-analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-14-09.

ObjectivesIn response to the COVID-19 pandemic there have been significant developments in research, its conduct and the supporting ethical framework. While many protocols have been delayed, halted or modified, other research efforts have been accelerated, generating controversy. The goal of this paper is to determine the rates of references surrounding the ethical oversight of research as reported in current COVID-19-related research publications.DesignScoping review.SettingPopulation-based observational or interventional studies from December 2019 to May 2020 with sample size of two or more. Studies were searched through electronic databases including Medline, EMBASE, and Cochrane CENTRAL Register of Controlled Trials.ParticipantsEligibility criteria included participants within published studies who tested positive for COVID-19.Main outcomes and measuresData were extracted and charting methods included taking note of references to ethical frameworks, institutional review board (IRB), ethics committee (EC) or research ethics board (REB) involvement, consent processes, and other variables.Results11 556 articles were screened, with 656 included in the final analysis. References to ethics were present in 530 (80.8%) studies, with 491 (74.8%) involving IRB/ECs/REBs and 126 (19.2%) not referencing ethics. Consent processes were outlined in 201 (30.6%) studies, with 198 (30.2%) reporting that they obtained consent waivers, however, 257 (39.2%) did not mention consent at all. Differences (pConclusionsThe majority of published articles pertaining to COVID-19 research made mention of ethical considerations, however, national and regional variations in research ethics review requirements introduce heterogeneity between studies and raise important questions about the conduct of scientific research during global public emergencies.Trial registration numberOpen Science Framework: https://osfio/z67wb.

Some thyroid cancer (TC) survivors experience cognitive symptoms. The purpose of this study is to perform a systematic literature review and meta-analysis comparing cognitive performance in TC survivors to controls. We performed a seven-database electronic search and hand-search. We performed duplicate independent reviews and data abstraction. Random effects meta-analyses reported standardized mean differences (SMDs) with 95% confidence intervals (CIs), where a negative value implies worse performance in the TC group. We reviewed 1174 unique citations and 10 full-text papers. We included seven studies of 241 treated TC survivors and 273 controls. Cognitive function was statistically significantly worse in TC survivors in the following domains: Attention and Concentration (Digit Span Forwards) SMD − 0.37 (95% CI − 0.62, − 0.13, p = 0.003, four studies), Speed of Processing (Trail Making A) SMD − 0.36 (95% CI − 0.66, − 0.05, p = 0.022, four studies), and Language (Controlled Oral Word Association [COWAT]-Categories) SMD − 0.97 (95% − 1.31, − 0.64, p

The prevalence of human papillomavirus (HPV) in squamous cell carcinoma of unknown primary in the head and neck (SCCUPHN), and prognosis by HPV status of SCCUPHN patients has been difficult to estimate because of the rarity of this subtype. In MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, EMBASE, Cochrane library and Web of Science searches, observational studies and clinical trials that reported survival rates of patients with SCCUPHN by HPV status were identified. Meta-analysis estimated the prevalence and prognosis (overall survival, OS; progression-free survival, PFS) of SCCUPHN by HPV status, and compared them to studies of oropharyngeal squamous cell carcinoma (OPSCC) from the same institutions and across continents. In 17 SCCUPHN studies (n = 1,149) and 17 institution-matched OPSCC studies (n = 6,522), the pooled HPV prevalence of SCCUPHN was 49%, which was only 10% (95%CI: 1-19%) lower than OPSCC prevalence in the underlying population. Estimated 5-year OS for HPV-negative SCCUPHN was 44% (95%CI: 36-51%) vs. HPV-positive SCCUPHN of 91% (95%CI: 86-96%); hazard ratio (HR) for OS was 3.25 (95%CI: 2.45-4.31) and PFS was 4.49 (95%CI: 2.88-7.02). HRs by HPV status for OPSCC were similar to that in SCCUPHN. While North American SCCUPHNs had higher HPV prevalence than European SCCUPHNs (OR = 2.68 (95%CI: 1.3-5.6)), HR of OS for HPV-negative vs. HPV-positive patients were similar in both continents (HRs of 3.78-4.09). Prevalence of HPV among SCCUPHN patients were lower than in OPSCC. The survival benefit conferred by being HPV-positive was similar in SCCUPHN as in OPSCCs, independent of continent.

PURPOSE/OBJECTIVE(S) The management of oligo-metastatic disease (OMD) is evolving, with increasing data supporting the use of stereotactic body radiotherapy. The aim of this systematic review and meta-analysis is to analyses health related quality of life (HRQOL) outcomes and the side-effects of SBRT in patients with OMD. MATERIALS/METHODS We searched MEDLINE, Epub Ahead of Print, EMBASE, Cochrane CT, Cochrane SR, Emcare, and PsycInfo databases (from inception to March 2020). Randomized clinical trials (RCTs) or observational studies were included if HRQOL outcomes were reported from patients with defined OMD (£5 metastases) who received SBRT as metastasis-directed therapy, and who completed validated HRQOL questionnaires at baseline and 12-months. Meta-analysis using weighted mean difference was performed to estimate a difference between baseline and 12-month scores. Secondary outcome, calculated by the pooled incidence rate approach using the inverse variance method, was the estimated event rate of clinically significant Common Terminology Criteria for Adverse Events (CTCAE) grade 2-4 and grade 5 toxicity, expressed per person-time of follow-up. Authors of studies included were contacted to obtain additional information. Methods adhered to PRISMA guidelines. RESULTS Four of 7,545 studies screened were eligible for inclusion. Two studies were phase II RCTs and two were prospective single arm studies. Among 277 patients who received SBRT, median follow-up was 31 months (range 24-41 months). Two studies included only prostate cancer patients and two studies included mixed histologies. Two studies measured European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and two measured Functional Assessment of Cancer Therapy - General (FACT-G) scores. Using a fixed effects model, the mean change in 12-month EORTC QLQ-C30 global health QOL score from baseline demonstrated a statistically significant decline (pooled weighted mean difference -5.2, 95% CI -9.3 to -1.2, both prostate cancer studies, 57 patients total). Meta-analysis of total FACT-G scores in the other two studies was not possible as mean difference results for one study were unavailable. For the available multi-histology study, no statistically significant difference was seen in baseline to 12-month mean FACT-G total scores in the SBRT arm. We estimated an event rate of 0.06 (95% CI: 0.024, 0.15) CTCAE grade 2-4 toxicities per person-year and 0.008 (95% CI: 0.002, 0.031) grade 5 toxicities per person-year. CONCLUSION Although a statistically significant decline in the EORTC QLQ C30 global health/QOL measure was seen, it was small and unlikely to be of clinical importance. Rates of SBRT-related clinical toxicities are low. There is limited QOL data published for patients with OMD, with varying HRQOL tools used.

Objective A sentinel lymph node biopsy is widely accepted as the standard of care for surgical staging in low-grade endometrial cancer, but its value in high-grade endometrial cancer remains controversial. The aim of this systematic review and meta-analysis was to evaluate the performance characteristics of sentinel lymph node biopsy in patients with endometrial cancer with high-grade histology (registered in the International Prospective Register of Systematic Reviews with identifying number CRD42020160280). Data Sources We systematically searched the MEDLINE, Epub Ahead of Print, MEDLINE In-Process & Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Embase databases all through the OvidSP platform. The search was performed between January 1, 2000, and January 26, 2021. ClinicalTrials.gov was searched to identify ongoing registered clinical trials. Study Eligibility Criteria We included prospective cohort studies in which sentinel lymph node biopsy were evaluated in clinical stage I patients with high-grade endometrial cancer (grade 3 endometrioid, serous, clear cell, carcinosarcoma, mixed, undifferentiated or dedifferentiated, and high-grade not otherwise specified) with a cervical injection of indocyanine green for sentinel lymph node detection and at least a bilateral pelvic lymphadenectomy as a reference standard. If the data were not reported specifically for patients with high-grade histology, the authors were contacted for aggregate data. Methods We pooled the detection rates and measures of diagnostic accuracy using a generalized linear mixed-effects model with a logit and assessed the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Results We identified 16 eligible studies of which the authors for 9 of the studies provided data on 429 patients with high-grade endometrial cancer specifically. The study-level median age was 66 years (range, 44–82.5 years) and the study-level median body mass index was 28.6 kg/m2 (range, 19.4–43.7 kg/m2). The pooled detection rates were 91% per patient (95% confidence interval, 85%–95%; I2=59%) and 64% bilaterally (95% confidence interval, 53%–73%; I2=69%). The overall node positivity rate was 26% (95% confidence interval, 19%–34%; I2=44%). Of the 87 patients with positive node results, a sentinel lymph node biopsy correctly identified 80, yielding a pooled sensitivity of 92% per patient (95% confidence interval, 84%–96%; I2=0%), a false negative rate of 8% (95% confidence interval, 4%–16%; I2=0%), and a negative predictive value of 97% (95% confidence interval, 95%–99%; I2=0%). Conclusion Sentinel lymph node biopsy accurately detect lymph node metastases in patients with high-grade endometrial cancer with a false negative rate comparable with that observed in low-grade endometrial cancer, melanoma, vulvar cancer, and breast cancer. These findings suggest that sentinel lymph node biopsy can replace complete lymphadenectomies as the standard of care for surgical staging in patients with high-grade endometrial cancer.

Importance Active surveillance is sometimes considered as a disease management option for individuals with small, low-risk papillary thyroid carcinoma. Objective To assess whether patient age is associated with progression of low-risk papillary thyroid carcinoma (tumor growth or incident metastatic disease) in adults under active surveillance. Evidence Review Eight electronic databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Emcare, PsycINFO, Web of Science, and ClincalTrials.gov) were searched from inception to March 2019, supplemented with a hand search. Two investigators independently screened citations, reviewed full-text articles, and abstracted data. Additional data were sought from authors. Random-effects meta-analyses were performed using incidence data (statistically adjusted for confounders and crude rates). Findings A total of 1658 unique citations were screened, and 62 full-text articles were reviewed, including 5 studies. Three studies included exclusively microcarcinomas and 2 included tumors up to 2 cm in maximal diameter. The mean age of participants was 51.0 to 55.2 years in 4 studies reporting this value. The mean or median follow-up was 5 years or more in 3 studies and approximately 2 years in 2 studies. The pooled risk ratio for tumor growth of 3 mm or more in maximal diameter in individuals aged 40 to 50 years or older compared with younger individuals was 0.51 when adjusted for confounders (95% CI, 0.29-0.89; 1619 patients, 2 studies), and the unadjusted risk ratio of this outcome for individuals 40 years or older was 0.55 (95% CI, 0.36-0.82; 2097 patients, 4 studies). In adults aged 40 to 45 years or older, the unadjusted risk ratio for any tumor volume increase compared with younger individuals was 0.65 (95% CI, 0.51-0.83; 1232 patients, 4 studies). The pooled risk ratio for incident nodal metastases in individuals 40 years or older was 0.22 (95% CI, 0.10-0.47; 1806 patients, 3 studies); however, in a secondary analysis, the risk difference was not significantly different. There was no statistically significant heterogeneity in any of the meta-analyses. There were no thyroid cancer–related deaths nor incident distant metastases. Conclusions and Relevance This study suggests that older age may be associated with a reduced risk of primary papillary thyroid carcinoma tumor growth under active surveillance. Incident metastatic disease is uncommon during active surveillance.

Objectives Heated intraperitoneal chemotherapy (HIPEC) has not been universally adopted at the time of interval cytoreductive surgery for primary epithelial ovarian cancer (EOC) despite evidence of a 12-month overall survival (OS) benefit in a recent landmark randomized trial. We performed a systematic review and meta-analysis to assess oncologic outcomes and perioperative morbidity following HIPEC among primary EOC patients. Methods We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, from inception to August 2019, for observational and randomized studies of primary EOC patients undergoing HIPEC. We assessed risk of bias using the Institute of Health Economics Quality Appraisal Checklist for single-arm cohort studies, Newcastle-Ottawa Scale for comparative cohort studies, and Cochrane Collaboration's Tool for randomized trials. We qualitatively summarized survival outcomes and calculated the pooled proportion of 30-day grade III-IV morbidity and postoperative death. Results: We identified 35 articles including 2252 primary EOC patients; one study was a randomized trial, and only six studies included a comparator group of surgery alone. The timing, temperature, and chemotherapeutic agents used for HIPEC differed across studies. Reported OS was highly variable (3-year OS range: 46–77%); three comparative cohort studies and the sole randomized trial reported statistically significant survival benefits for HIPEC over surgery alone, while two comparative cohort studies did not. The pooled proportions for grade III-IV morbidity and postoperative death at 30 days were 34% (95% CI 20–52) and 0% (95% CI 0–5) respectively. Conclusion One randomized trial suggests that HIPEC at time of interval cytoreductive surgery should be considered in patients with primary EOC. However, there is significant heterogeneity in literature with respect to an appropriate HIPEC regimen, short- and long-term outcomes. High-quality prospective randomized trials are urgently needed to clarify the role of HIPEC in the first-line treatment of primary EOC.

Background: The potential risk of subsequent malignant neoplasms (SMNs) after radioactive iodine (RAI) treatment of thyroid cancer (TC) is an important concern. Methods: A systematic review was upd...

PURPOSE To evaluate the performance of 18 F-fluorodeoxy-d-glucose positron emission tomography-computed tomography (18 F-FDG PET/CT) in identifying local failure and regional failure following curative radiotherapy or surgery for head and neck squamous cell carcinoma. METHODS A comprehensive literature search identified studies published between January 2010 and August 2016. Diagnostic performance of 18 F-FDG PET/CT was evaluated for local failure/regional failure stratified by treatment-to-scan time interval of ≤3 versus >3 months. RESULTS Twenty-four studies (2627 patients) were included. Compared to ≤3 months, 18 F-FDG PET/CT performed >3 months showed significantly improved sensitivity (87% vs 60%, P = 0.020) and specificity (93% vs 84%, P 3 versus ≤3 months. CONCLUSIONS This meta-analysis confirms high specificity but modest sensitivity of posttreatment 18 F-FDG PET/CT for local failure and regional failure. Sensitivity and specificity are significantly improved when 18 F-FDG PET/CT is performed >3 months for local failure.

Background Increasing demands on health care systems require patients to take on more active roles in their health. Effective self-management has been linked to improved health outcomes, and evidence shows that effective self-management is linked to health literacy (HL). HL is an important predictor of successful self-management in other chronic diseases but has had minimal testing in cancer. Methods A scoping review was conducted to examine and summarize what is known about the association between HL and self-management behaviors and health service utilization in the cancer setting. The methodological framework articulated by Arksey and O'Malley was used and was further refined with the Joanna Briggs Institute methodology. Inclusion criteria included the following: peer review; publication in English; and adult patients and caregivers of all races, ethnicities, and cultural groups. Use of a validated instrument to measure HL was required. Results The search yielded 2414 articles. After the removal of duplicates and the performance of title scans and abstract reviews, the number was reduced to 44. Of the 44 full-text articles reviewed, 17 met the inclusion criteria. A number of important self-management behaviors and related outcomes were found to be associated with HL. These included the uptake of cancer screening, the receipt of prescribed chemotherapy, and a greater risk of postoperative complications. Conclusions This literature review shows that HL is associated with important self-management behaviors in cancer. The implications of these associations for individuals with inadequate HL and for the health care system are significant. More research is needed to explore these associations.

Background: Progression free-survival (PFS) is the dominant endpoint in phase 3 randomized controlled trials (RCTs) in women with metastatic breast cancer (MBC), and requires the ability to measure target lesions. It is unknown whether treatment effect on PFS is consistent among patients with measurable and non-measurable disease. Methods: We searched MEDLINE, EMBASE and COCHRANE for phase 3 RCTs in MBC that reported outcomes in subgroups with non-measurable (or bone only disease, if not reported explicitly) and measurable disease. Data were extracted and a single hazard ratio (HR) and 95% confidence intervals (CI) were computed to compare the individual trial treatment effect in non-measurable versus measurable disease. Data were then pooled in a meta-analysis. We repeated the analysis comparing bone only to non-bone only disease and performed subgroup analyses based on drug mechanism of action. Results: Of 82 RCTs that enrolled patients with non-measurable disease, 16 trials comprising 8516 patients were eligible for analysis. All included RCTs used PFS or time to progression as primary endpoints. There was no difference in pooled treatment effect between patients with non-measurable and measurable disease (HR 1.01, 95% CI 0.89-1.15, p=0.82). However, compared to non-bone only disease, a significantly greater effect on PFS was seen in those with bone only disease (HR 0.82, 95% CI 0.70-0.98, p=0.03). Subgroups analyses according to drug mechanism are shown in Table 1 Intra-study comparison, according to evaluated drug mechanismCohort/ Investigational drugNo. studies includedMeasurable HR (95% CI)Non measurable HR (95% CI)Intra- study comparison HR (95% CI)P – for intra-study comparisonAll160.69 (0.65-0.73)0.72 (0.64-0.80)1.01 (0.89-1.15)0.82Chemotherapy30.99 (0.87-1.13)0.67 (0.44-1.02)0.73 (0.44-1.21)0.22Endocrine treatment40.86 (0.77-0.96)0.94 (0.80-1.10)1.13 (0.92-1.40)0.23Signal transduction inhibitors40.52 (0.48-0.57)0.41 (0.33-0.50)0.74 (0.59-0.94)0.01Anti-angiogenetic agents50.66 (0.59-0.73)0.84 (0.67-1.04)1.34 (1.05-1.71)0.02CI- confidence interval, HR- hazard ratio . Compared to patients with measurable disease, there was a greater effect on PFS in those with non-measurable disease in RCTs of signal transduction inhibitors and endocrine therapy (HR 0.74, 95% CI 0.59-0.94, p=0.01). There was a lesser effect on PFS in patients with non-measurable disease in RCTs of antiangiogenic drugs (HR 1.34, 95% CI 1.05-1.71, p=0.02). Comparable effect on PFS was shown in RCTs evaluating endocrine therapy and chemotherapy. Conclusions: There is variability in treatment effect on PFS in patients with measurable and non-measurable disease. There is greater effect on PFS in RCTs of endocrine therapy and signal transduction inhibitors and in patients with bone only disease. Standardization of PFS determination in patients with non-measurable and bone only disease is warranted. Citation Format: Goldvaser H, Ribnikar D, Fazelzad R, Seruga B, Templeton AJ, Ocana A, Amir E. Influence of non-measurable disease on progression-free survival in patients with metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-17-02.

Purpose Current guidelines recommend somatic genomic sequencing for patients with advanced pancreatic cancer to identify targetable alterations amenable to targeted therapy. The benefit of somatic genomic sequencing in pancreatic cancer remains unclear. This study aims to assess the evidence supporting genomic sequencing to inform treatment selection for patients with advanced pancreatic cancer. Methods A systematic review identified prospective studies of exocrine pancreatic cancer patients published before August 2020 which conducted genomic sequencing to inform treatment selection. Outcomes of interest included the proportion of patients with targetable alterations, the proportion that received targeted treatments, and the impact of targeted treatments on overall survival. Meta-analysis for proportions and hazard ratios was performed using Dersimonian and Laird random effect models. Results 19 studies (representing 2048 pancreatic cancer patients) were included. Sequencing methodologies, definitions of targetable alterations, and approaches treatment selection varied across studies and were incompletely reported. 590 of 1382 sequenced patients harboured a targetable alteration (random effects meta-analysis estimate of the proportion 0.46, 95% confidence interval 0.32–0.61). The proportion of patients with targetable alterations was highly heterogenous between studies (I2 93%, P Conclusions Genomic sequencing frequently identifies targetable alterations in pancreatic cancers. Further research is required to standardize the definitions of targetable alterations, the approach to treatment matching, and quantify the benefit of targeted therapy.

Background Although combined oral contraceptives (COC) are considered a transient risk factor for venous thromboembolism (VTE), the risk of recurrence after discontinuation of anticoagulation is unclear. Few studies have focused on the risk of recurrence in this group; studies report variable results and are limited by small sample size. The risk of recurrence appears to be low, but this could relate to the young age of affected women. Deciphering the absolute VTE recurrence risk after a COC-associated VTE is crucial in helping clinicians and patients decide if anticoagulation could be discontinued after the initial treatment period. Objectives The objectives of this systematic review and meta-analysis are to estimate the incidence of recurrent VTE among women with COC-associated VTE, compared with women with unprovoked VTE. Methods We searched the following databases: Cochrane Central Register of Controlled Trial, Cochrane Database of Systematic Reviews, Embase Classic +Embase, and Medline ALL, all from the OvidSP platform, from the database's inception to July 2020. Additional studies were identified by screening citations from included studies. Prospective cohort studies, randomized controlled trials (RCTs), and meta-analyses of prospective cohort studies or RCTs were reviewed by two authors for study inclusion (Figure 1). Studies were included if women had objectively confirmed COC-associated VTE, received a minimum of three months of anticoagulation, discontinued COC prior to or at time of discontinuation of anticoagulation, time of follow-up began after anticoagulation was stopped, and recurrent VTE data was available. Studies were excluded if patients were systematically treated with an alternative pharmacologic agent intended to reduce the risk of recurrent VTE such as aspirin. Authors of identified papers were contacted for additional data on critical variables. If there were multiple publications from a cohort, the study with the longest follow up was included. Two authors extracted study data and assessed included studies for risk of bias using the Newcastle Ottawa Scale. Meta-analysis was done using a random effects Poisson regression model. Heterogeneity was assessed using the I-squared measure. Results Our systematic review included 19 studies with a total of 1,537 women (5,828 patient years of follow up) with an index COC-associated VTE, and 1,974 women (7,798 patient years of follow up) with an index unprovoked VTE. Authors contributed additional unpublished data in 16 of the 19 studies. Overall, studies were at low risk of bias, with a mean of 7 stars (out of a possible 9) in the Newcastle Ottawa Scale. Among the 19 studies, the incidence rate of VTE recurrence in women with COC-associated VTE was 1.22 per patient year (95% confidence interval (CI) 0.94 to 1.59, I 2 = 6.4%, 95% prediction interval (PI) 0.81 to 1.85) (Figure 2). The incidence rate of VTE recurrence in women with an index unprovoked VTE not associated with COC was 3.89 per patient year (95% CI 2.98 to 5.07, I 2 =74.2%, 95% PI 1.37 to 11.03). The unadjusted incidence rate ratio of recurrent VTE comparing women with COC-associated events to women with unprovoked events was 0.34 (95% CI 0.26 to 0.45, I 2 = 2.6%, 95% PI 0.26 to 0.46). Only three studies had age-adjusted comparisons, but each with a different effect measure so they could not be combined, with a relative risk ratio 0.4 (95% CI 0.2 to 0.8) (also adjusted for site of VTE and congenital thrombophilia) (Eischer 2014), a hazard ratio of 0.11 (95% CI 0.01 to 0.85) (Kearon 2019), and an incidence rate ratio of 1 (95% CI 0.3 to 3.2) (Le Moigne 2013). Conclusions The estimated risk of VTE recurrence after a COC-associated VTE is low, and is lower compared to women with unprovoked VTE, however this comparison may be confounded by age. With only a minority of studies providing age adjusted analyses, the true difference remains unknown. Our meta-analysis is strengthened by the substantial contribution of unpublished data from individual study authors. This can help to guide clinicians and patient shared decision-making on the duration of anticoagulation. Figure 1 Figure 1. Disclosures Le Gal: LEO Pharma: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Bayer: Honoraria; Aspen: Honoraria; Sanofi: Honoraria. Schulman: Boehringer-Ingelheim: Research Funding; Octapharma: Research Funding. Skeith: CSL Behring: Research Funding; Leo Pharma: Honoraria; Sanofi: Honoraria.

Purpose The addition of platinum agents to anthracycline and taxane-based chemotherapy in early-stage triple negative breast cancer (TNBC) patients improves pathological complete response (pCR). Long-term outcomes, such as disease-free survival (DFS) and overall survival (OS), have not been well-established. Methods A systematic literature review identified studies using platinum-based treatment in TNBC patients in the neoadjuvant or adjuvant setting with reportable long-term outcomes. Hazard ratios (HR) from collected data were pooled in a meta-analysis using generic inverse-variance and random effects modeling. Subgroup analyses were conducted based on treatment setting and study design. Results Fourteen studies comprising 3518 patients met the inclusion criteria. Median follow up was 56.2 months. All studies reported DFS and 9 studies (64%) reported OS. DFS was significantly better in platinum-based treatment (HR 0.71, 95% confidence interval (CI) 0.56–0.89; p = 0.03). However, OS was no different (HR 0.98, 95% CI 0.75–1.27; p = 0.87). There was a non-significant difference between platinum exposure in the adjuvant compared to neoadjuvant setting for both DFS (HR 0.75 vs 0.62, p = 0.43) and for OS (HR 0.90 vs 1.10, p = 0.58). The addition of platinum was associated with more thrombocytopenia and all-grade neuropathy and non-significant increases in neutropenia and grade 3–4 neuropathy. Conclusions Platinum-based treatment improves DFS but not OS. The reporting of toxicity was suboptimal, but in general adding platinum increased toxicity. The discordant effect of platinum-based treatment on DFS and OS suggest the potential development of platinum resistance and worse outcomes after recurrence. Platinum-based chemotherapy cannot be recommended in unselected patients with early TNBC.

IntroductionCommunicable disease epidemics and pandemics magnify the health inequities experienced by marginalised populations. People who use substances suffer from high rates of morbidity and mortality and should be a priority to receive palliative care, yet they encounter many barriers to palliative care access. Given the pre-existing inequities to palliative care access for people with life-limiting illnesses who use substances, it is important to understand the impact of communicable disease epidemics and pandemics such as COVID-19 on this population.Methods and analysisWe will conduct a scoping review and report according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews reporting guidelines. We conducted a comprehensive literature search in seven bibliographical databases from the inception of each database to August 2020. We also performed a grey literature search to identify the publications not indexed in the bibliographical databases. All the searches will be rerun in April 2021 to retrieve recently published information because the COVID-19 pandemic is ongoing at the time of this writing. We will extract the quantitative data using a standardised data extraction form and summarise it using descriptive statistics. Additionally, we will conduct thematic qualitative analyses and present our findings as narrative summaries.Ethics and disseminationEthics approval is not required for a scoping review. We will disseminate our findings to healthcare providers and policymakers through professional networks, digital communications through social media platforms, conference presentations and publication in a scientific journal.

21 Background: The Choosing Wisely (CW) campaign launched in 2012 includes oncology-related recommendations (CWR) aimed at promoting evidence-based care and de-implementing low value practices; however, it remains unclear to what extent practice has changed as a result of the campaign. We undertook a scoping review to evaluate the extent of CWR uptake in oncology, and barriers and facilitators to implementation. Methods: A systematic search of MEDLINE, EMBASE, Cochrane, Emcare Nursing and Scopus was conducted for articles published between 2012 and March 6, 2020 pertaining to cancer-specific CWR. Articles were excluded if they did not report on cancer-specific recommendations, were commentaries/opinions, reported on screening or prevention, focused on pediatric populations, or were not in English. Retained articles were thematically grouped based on study objective. Implementation strategies, barriers and facilitators were summarized for articles implementing a recommendation into practice. Results: The search yielded 8565 articles; 98 articles were retained, addressing 32 unique recommendations. Use of active surveillance for low-risk prostate cancer (14/98) and reduction of imaging in early breast cancer (13/98) were the most commonly evaluated CWR. Of the 29 articles reporting on pre-post CW campaign adherence, 20 reported improved compliance without further intervention. In articles evaluating factors associated with CWR-concordance (62/98), age (23/62), stage or risk (22/62), and geographic location (21/62) most commonly influenced care decisions. Few articles described the development of interventions to improve concordance (1/98) or a protocol to evaluate implementation (2/98) with no further testing of their design. Of the 10/98 articles that evaluated implementation of a CWR, all reported improved compliance (range: 3-73% improvement). Implementation strategies were used in combination and most often included provider education (8/10), stakeholder engagement (6/10), and forced function (4/10). Preconceived views and reluctance to adopt new practices were the most commonly reported barriers to implementation; the use of technology to update practice and the use of education and evidence to build provider buy-in were the most common facilitators. Conclusions: In the eight years since the initial publication of oncology-specific CW recommendations, uptake has been limited. Publication of the recommendations has resulted in some passive improvements in care. Further adoption of CWR likely requires an implementation strategy that includes building stakeholder buy-in, and utilization of updated order sets and forced functions in technology to facilitate change. Future studies should assess the impact of the COVID-19 pandemic on the adoption of CWR and the de-implementation of low-value care.

Background The presence of non-measurable disease is common in metastatic breast cancer. It is unknown whether treatment effect on progression free survival (PFS) is consistent among patients with measurable and non-measurable disease. Methods A systematic literature search identified phase III randomized controlled trials (RCTs) in metastatic breast cancer that reported outcomes in patients with non-measurable and measurable disease. Hazard ratios (HRs) and 95% confidence intervals were computed to compare the individual trial treatment effect on PFS in non-measurable versus measurable disease. Analyses were repeated for bone-only compared to non-bone-only disease and based on drug mechanism of action. Results Among 82 RCTs that enrolled patients with non-measurable disease, data were available from 16 trials comprising 8516 patients. Treatment effect on PFS was similar in patients with non-measurable and measurable disease (HR for intra-study comparison = 1.01, p = 0.82). However, compared to non-bone-only disease, a significantly greater effect on PFS was seen in those with bone-only disease (HR 0.83, p = 0.03). Compared to patients with measurable disease, there was a greater effect on PFS in those with non-measurable disease in RCTs of signal transduction inhibitors and endocrine therapy (HR 0.74, p = 0.01) and a lesser effect on PFS in RCTs of antiangiogenic drugs (HR 1.34, p = 0.02). Comparable effect on PFS was shown in RCTs evaluating endocrine therapy (HR 1.13, p = 0.23) and chemotherapy (HR 0.73, p = 0.22). Conclusions There is variability in treatment effect on PFS in patients with measurable and non-measurable disease, especially those with bone-only disease. Standardization of PFS determination in these patients is warranted.

Background The relative efficacy of interventions for primary prevention of anthracycline-associated cardiotoxicity is unknown. Methods We conducted a systematic review of randomized controlled trials for primary prevention of anthracycline-associated cardiotoxicity in adult cancer patients. We used hierarchal outcome definitions in the following order of priority: (1) composite of heart failure or decline in left ventricular ejection fraction, (2) decline in ejection fraction, or (3) heart failure. Data were analyzed using a Bayesian network meta-analysis with random effects. Results A total of 16 trials reported cardiotoxicity as a dichotomous outcome among 1918 patients, evaluating dexrazoxane, angiotensin antagonists, beta-blockers, combination angiotensin antagonists and beta-blockers, statins, Co-enzyme Q-10, prenylamine, and N-acetylcysteine. Compared with control, dexrazoxane reduced cardiotoxicity with a pooled odds ratio (OR) of 0.26 (95% credible interval [CrI] 0.11–0.74) and had the highest probability (33%) of being most effective. No other agent was demonstrably better than placebo. Angiotensin antagonists had an 84% probability of being most effective in a sensitivity analysis excluding one outlying study (OR 0.06 [95% CrI 0.01– 0.24]). When the outcome was restricted to heart failure, dexrazoxane was associated with an OR of 0.12 (95% CrI 0.06–0.23) relative to control and had 58% probability of being most effective, while angiotensin antagonists had an OR of 0.18 (95% CrI 0.05–0.55). Available data suggested that dexrazoxane and angiotensin antagonists did not affect malignancy response rate or risk of death. Conclusion Moderate quality data suggest that dexrazoxane, and low quality data suggest angiotensin antagonists, are likely to be effective for cardiotoxicity prevention.

Background: The standard of care in management of hypothyroidism is treatment with levothyroxine (L-T4). Sometimes patients are dissatisfied with L-T4 and the combination of levo-triiodothyronine (L-T3) with L-T4 is considered. Methods: We performed a systematic review and meta-analysis of blinded randomized controlled trials (RCTs), reporting how often hypothyroid patients prefer combination L-T3/L-T4 treatment to L-T4 alone. We also explored for explanatory factors for combination therapy preference in sensitivity analyses examining trial, patient, and disease characteristics. Potential dose-response relationships were explored using meta-regression analyses. We searched 9 electronic databases (from inception until February, 2019), supplemented with a hand-search. Two reviewers independently screened abstracts and citations and reviewed full-text papers, with consensus achieved on the included studies. Two reviewers independently critically appraised the quality of included studies and abstracted the data. Random effects meta-analyses were reported for the percentage of patients preferring combination L-T3/T-T4 therapy over L-T4 alone. A binomial distribution of choices (i.e., preference of combination therapy or no preference for combination therapy) was assumed. Results: We included 7 blinded RCTs including 348 hypothyroid individuals in the primary meta-analysis. The pooled prevalence rate for preference of combination therapy over L-T4 was 46.2% (95% confidence interval 40.2%, 52.4%) (p = 0.231 for the difference from chance). There was no significant statistical heterogeneity among study results (Q = 7.32, degrees of freedom = 6, p = 0.293, I2 = 18.0%). In sensitivity analyses, combination treatment preference was explained in part by treatment effects on TSH concentration, mood and symptoms, but not quality of life nor body weight. In a secondary dose-response meta-regression analyses, a statistically significant association of treatment preference was identified for total daily L-T3 dose, but not L-T3:L-T4 dose ratio. Conclusions: In conclusion, in RCTs in which patients and investigators were blinded to treatment allocation, approximately half of participants reported preferring combination L-T3 and L-T4 therapy compared to L-T4 alone; this finding was not distinguishable from chance. An observed potential positive L-T3 dose effect on treatment preference deserves further study, with careful consideration of thyroid biochemical indices and patient reported outcomes.

Background Globally, the rising cost of anticancer therapy has motivated efforts to quantify the overall value of new cancer treatments. Multicriteria decision analysis offers a novel approach to incorporate multiple criteria and perspectives into value assessment. Methods The authors recruited a diverse, multistakeholder group who identified and weighted key criteria to establish the drug assessment framework (DAF). Construct validity assessed the degree to which DAF scores were associated with past pan-Canadian Oncology Drug Review (pCODR) funding recommendations and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS; version 1.1) scores. Results The final DAF included 10 criteria: overall survival, progression-free survival, response rate, quality of life, toxicity, unmet need, equity, feasibility, disease severity, and caregiver well-being. The first 5 clinical benefit criteria represent approximately 64% of the total weight. DAF scores ranged from 0 to 300, reflecting both the expected impact of the drug and the quality of supporting evidence. When the DAF was applied to the last 60 drugs (with reviewers blinded) reviewed by pCODR (2015-2018), those drugs with positive pCODR funding recommendations were found to have higher DAF scores compared with drugs not recommended (103 vs 63; Student t test P = .0007). DAF clinical benefit criteria mildly correlated with ESMO-MCBS scores (correlation coefficient, 0.33; 95% CI, 0.009-0.59). Sensitivity analyses that varied the criteria scores did not change the results. Conclusions Using a structured and explicit approach, a criterion-based valuation framework was designed to provide a transparent and consistent method with which to value and prioritize cancer drugs to facilitate the delivery of affordable cancer care.

3089 Background: Oncogenic nonV600 BRAF mutations (muts) can be classified according to distinct molecular characteristics. TT strategies for class 2 and 3 BRAF muts have not been established. In recent years there have been numerous reports of clinical activity for various TT in pts with nonV600 muts. We performed a systematic scoping review and meta-analysis to assess treatment outcomes with MAPK TT according to BRAF class, cancer type and TT type. Methods: An extensive literature search was conducted from 2010-20. All studies were independently reviewed and extracted by 2 reviewers and in accordance with PRISMA guidelines. Individual patient level data were collected and analyzed from studies that met the following inclusion criteria: published reports of 1) advanced cancer pts with; 2) class 2 or class 3 nonV600 BRAF muts; 3) who received MAPK TT; 4) with treatment response (TR) data available. Primary outcome was overall TR rate (TRR). To assess differences between groups, odds ratios (OR) were calculated using a multi-level mixed-effects logistic regression model. Results: 15,171 studies were screened and 168 were included for data extraction. We identified 100 studies with a total of 396 pts that met inclusion criteria. There were 17 reports (161 pts) of prospective clinical trials and 83 retrospective studies (235 pts). RECIST criteria were used for TR assessment in 183 (46%) pts. The entire study included 280 pts with class 2 and 116 pts with class 3 BRAF muts. Overall, 111 (28%) pts achieved a TR. TRR according to primary tumor type, BRAF class, and TT type is indicated in Table. TRR was lower in reports of prospective studies compared to retrospective studies (OR 0.14, P = 0.002), and in studies that employed RECIST criteria vs. those that didn’t (OR 0.29, P = 0.044). TRR was higher among pts with class 2 muts vs. those with class 3 muts (OR 2.21, P = 0.042). Conclusions: These data establish that MAPK TT have demonstrated clinical activity in cancers with oncogenic nonV600 mutations, and that BRAF mutation class may dictate responsiveness to different TT strategies. TRR may be over-estimated in the retrospective literature. This analysis will be valuable for molecular tumor boards and to guide future clinical trial design. Prospective clinical trials of TT in this pt population are warranted.[Table: see text]

Purpose: The aims of this meta-analysis are to evaluate the diagnostic performance and to explore the optimal timing of post-treatment 18F-FDG PET/CT for HNSCC. Methods: January 2010 to August 2016 was the range for study selection. Subgroup analyses were performed for local/regional failure stratified by treatment-to-scan time interval of ≤3 vs. >3 months. Results: Twenty-four studies (2,256 patients) were included. Compared to ≤3 months, 18F-FDG PET/CT performed >3 months showed significantly improved sensitivity (87% vs. 60%, p=0.020) and specificity (93% vs. 84%, p3 months vs. ≤3 months (95% vs. 97%, p=0.35). Conclusions: This meta-analysis showed high NPV but modest PPV for post-treatment 18F-FDG PET/CT for local and regional failure. Sensitivity is improved if performed >3 months for local failure and marginally improved for regional failure. Citation Format: Erin T. Wong, Adam A. Dmytriw, Eugene Yu, John Waldron, Rouhi Fazelzad, John de Almeida, Patrick Veit-Haibach, Brian O’Sullivan, Wei Xu, Shao Hui Huang. Diagnostic performance and timing of post-treatment 18F-FDG PET/CT for head and neck cancer surveillance: A meta-analysis of reported studies [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A35.

e19121 Background: The programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) pathway plays a crucial role in cancer immuno-surveillance and is the target of approved immunotherapeutic drugs. Available data suggest a variable prognostic impact of PD-L1 expression in solid tumors. Methods: A systematic literature search of electronic databases identified publications exploring the effect of PD-L1 on overall survival (OS) and/or progression-free survival (PFS). Hazard ratios (HR) were pooled in a meta-analysis using generic inverse-variance and random effects modeling. Subgroup analyses were conducted based on disease site, stage of disease, and method of PD-L1 quantification using the Deeks method. Results: One hundred eighty-eight studies comprised of 212,748 patients met the inclusion criteria. PD-L1 expression was associated with worse OS (HR 1.32, 95% confidence interval (CI) 1.25 - 1.38; P < 0.001). There was significant heterogeneity between disease sites (subgroup P = 0.002) with pancreatic, hepatocellular and genitourinary cancers being associated with the highest magnitude of adverse outcome (Table). PD-L1 was also associated with worse overall PFS (HR 1.19, 95% CI 1.09 - 1.30; P < 0.001). Stage of disease did not significantly affect the results (subgroup P = 0.52), nor did the method of quantification (immunohistochemistry or mRNA) (subgroup P = 0.70). Conclusions: High expression of PD-L1 is associated with worse cancer outcomes albeit with significant heterogeneity between disease sites. The effect seems consistent in early stage and metastatic disease and is not sensitive to method of PD-L1 quantification. [Table: see text]

Objective.Research on psoriatic arthritis mutilans (PAM), the most severe form of psoriatic arthritis, is impeded by the lack of an accepted classification criteria. We performed a systematic review of the literature to identify and synthesize clinical and radiographic features associated with the definition of PAM.Methods.A systematic literature search limited to human studies was conducted without language restriction. Abstracts were independently screened by 2 investigators and studies that reported information on patients with PAM were included. A standardized form was used to independently collect clinical and radiographic items defining PAM, patient’s demographics, disease characteristics, and outcomes.Results.There were 8570 citations searched to identify 112 articles for full review and 58 articles for data abstraction. We identified 8 definitions of PAM that were used in 283 subjects with a mean age ± SD at diagnosis of PsA of 33.9 ± 8.2 years. Disease manifestations (prevalence) included dactylitis (29–64%), enthesitis (29–32%), axial disease (14–27%), and nail lesions (47%). PAM definitions include 1 (n = 2 studies) or more (n = 14 studies) joints involving interphalangeal, metacarpophalangeal, or metatarsophalangeal joints. The most prevalent PAM clinical features were digital telescoping (34%), digital shortening (33%), and flail joints (22%). The most prevalent PAM radiographic items were bone resorption (41%), pencil-in-cup change (16%), total joint erosions (14%), ankylosis (21%), and subluxation (7%).Conclusion.We have identified 8 definitions of PAM, and synthesized the clinical and radiographic items that are important for the classification of PAM. We have established the groundwork for future development classification criteria for PAM.

INTRODUCTION Hemoglobinopathies, such as sickle cell disease (SCD) and thalassemia, are chronic blood disorders with a profound impact on a patient's life expectancy and quality. Patients often come from marginalized populations with variable health literacy. Prior studies have demonstrated improved outcomes in chronic illness as a result of empowering patients through various education strategies. This systematic review investigates the current state of patient education for SCD and thalassemia with the goal of elucidating which strategies have been effective in improving patient knowledge and/or ability to cope with illness. METHODS Literature was searched up to August 2018 in Medline, PsycINFO, Scopus, CINAHL, Cochrane Central, Cochrane Database of Systematic Reviews, EMBASE, Emcare, and the International Clinical Trials Registry Platform (ICTRP). Randomized controlled trials (RCTs) examining the effects of patient education on patients aged 18 years and older or transitioning into adulthood were included. Psychological interventions were excluded. Preliminary analysis focused on three outcomes: disease knowledge, self-efficacy, and coping ability. Meta-analysis was performed using RevMan 5.3. A random effects model with the inverse variance method was chosen. Standardized mean difference (SMD) was calculated for continuous outcomes due to the different scales used by each study. Changes from baseline with missing standard deviations were imputed from known standard deviations from other studies (Higgins 2011). Heterogeneity was evaluated using the I2 statistic. Domain-based approach was used to assess risk of bias (Higgins 2011). RESULTS The search yielded 12173 citations, 3575 were duplicates. Two reviewers screened the title and abstracts for full text retrieval. Of the 28 full-text citations reviewed, 8 met the inclusion criteria, representing 6 unique RCTs. Of the 6 RCTs, 2 were at high risk of attrition bias. The other domains generally exhibited an unclear risk of bias. Improvement in patient knowledge was a measured outcome in 3 RCTs totalling 351 participants with SCD, mostly of African-American descent. Standard deviations (SD) were lacking in the baseline and 6 month knowledge questionnaire results from Krishnamurti 2018. Attempts to impute the SDs were unsuccessful. Meta-analysis was conducted in the remaining 2 RCTs (n=274). Statistically significant SMD of 0.39 (95% CI 0.05 to 0.72, p=0.02, Figure 1A) in favour of the intervention group with low heterogeneity (I2=24%). These interventions were delivered as either a web-based multimedia education program or in a classroom setting. An increase in self-efficacy was reported in 2 RCTs (n=67) with a statistically significant SMD of 0.72 (95% CI 0.22 to 1.22, p=0.005, Figure 1B) in favour of patient education with no observed statistical heterogeneity (I2=0). Coping ability was reported in 2 RCTs (n=107) but one study was excluded from analysis due to lack of sufficient randomization data. For the remaining study (n=40), the SMD at 0.16 was not statistically significant (95% CI -0.46 to 0.78, p=0.60, Figure 1C). CONCLUSIONS This review summarizes the current state of patient education for adult hemoglobinopathy patients in which some efforts have been made for SCD but no comparable interventions exist for thalassemia. Interventions demonstrated a significant effect on improvement in knowledge and self-efficacy. However, this effect is of uncertain clinical significance due to lack of reporting on clinically relevant illness and healthcare utilization-related outcomes. Only one RCT adequately reported on improvement in coping ability with no statistical significance. Given these results, there is currently insufficient evidence to determine what intervention strategies might benefit adult patients with hemoglobinopathies. This review is limited by the paucity of high-quality RCTs addressing the impact of patient education on self-management. Notably, a considerable volume of studies that employ a non-RCT design were identified and also warrant appropriate analysis. Rigorously designed trials are needed to draw clinically-relevant conclusions regarding type and effectiveness of patient education for adult hemoglobinopathy patients. REFERENCE: Higgins JPT, Green S (eds.). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration, 2011. Disclosures Kuo: Agios: Consultancy; Alexion: Consultancy, Honoraria; Apellis: Consultancy; Bioverativ: Other: Data Safety Monitoring Board; Bluebird Bio: Consultancy; Celgene: Consultancy; Novartis: Consultancy, Honoraria; Pfizer: Consultancy.

247 Background: Creation of a culture of safety in healthcare organizations is fundamentally important to patient safety. However, there is limited guidance on how to effectively promote a culture of safety in healthcare settings including in oncology. We performed a systematic review to identify interventions or strategies to promote safety culture in cancer care. Methods: Medical Subject Headings and text words for “safety culture” and “cancer care” were combined to conduct structured searches in MEDLINE, EMBASE, CDSR, CINAHL, Cochrane CENTRAL, Epub Ahead of Print & In-Process, PsycINFO, Scopus, and Web of Science databases, for peer-reviewed articles published between 1999 and 2017. Articles were included if they described an intervention or strategy to promote safety culture in an oncology setting, and quantitative outcomes were reported. Study quality was assessed using the ROBINS-I risk of bias tool. Results: We screened 21,572 studies, of which 46 underwent full-text review, and 19 met the inclusion criteria. Studies described interventions in radiation oncology (15 articles), medical oncology (3), and general oncology (1) settings in either North America (15) or Europe (4). The most common experimental designs were interrupted time series (10) or before-and-after comparisons (6), and were of either moderate (89%) or severe (11%) risk of bias. Interventions varied but could be broadly categorized as incident learning systems (8), quality improvement programs (7), provider education programs (2), a provider scheduling system (1), and a patient safety champion intervention (1). While 89% of studies reported improvement in safety culture, there was substantial heterogeneity in evaluated outcomes. Most assessed provider outcomes such as number of reported adverse events (11) or Agency for Healthcare Research and Quality Safety Culture survey results (7). Conclusions: Despite a growing evidence base to identify interventions to promote safety culture in cancer care, definitive recommendations were difficult to make due to heterogeneity in study designs and outcomes. Given the importance of safety culture in cancer care, additional high-quality studies and standardization of outcome measures are needed.

e17093 Background: Heated intraperitoneal chemotherapy (HIPEC) following cytoreductive surgery in the treatment of primary epithelial ovarian cancer (EOC) after neoadjuvant chemotherapy was associated with a significant 12 months improved overall survival (OS) in a well-designed randomized controlled trial. Nonetheless, there remains uncertainty about the benefit and safety of HIPEC in ovarian cancer. The aim of this review was to assess efficacy and safety of HIPEC in primary EOC. Methods: We conducted a systematic search in Medline, Embase, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, from inception to February 22nd 2018 for observational and randomized studies of patients with primary EOC undergoing HIPEC at cytoreductive surgery with no language restrictions . We assessed risk of bias with the Institute of Health Economics Quality Appraisal Checklist for single-arm studies, and Newcastle-Ottawa Quality Scale for double-arm studies. We determined the pooled proportion of 30-day grade 3-4 morbidity, reoperation, and postoperative death. Results: Thirty-five articles including 1937 patients with primary EOC met inclusion criteria. Timing of HIPEC and type of chemotherapy regimens were not consistent between studies. There was significant variation in the reported OS of patients treated with HIPEC at cytoreductive surgery for primary EOC (3-year OS:48-77%; 5-year OS:17-72%). Thirteen articles were including in a meta-analysis to determine to the safety of HIPEC. The pooled proportions for 30-day Grade 3-4 morbidity, 30-day reoperation, and 30-day postoperative death were 33.0% (95% CI 23.0-45.0), 9.0% (95% CI 5.0-17.0) and 3.0% (95% CI 1.0-5.0) respectively. Conclusions: The use of HIPEC in primary EOC is associated with significant morbidity. There is significant heterogeneity in current literature. Higher quality, large prospective randomized control trials are needed to further support the benefit of HIPEC at cytoreductive surgery in the first-line treatment of primary EOC.

511 Background: Penile cancer is rare and there are scant data on the optimal chemotherapy regimen. The majority of trials are single arm, non-randomized studies. Here we report on a systematic review aiming to compare taxane combination chemotherapy regimens with non-taxane regimens for APC. Methods: A systematic review was conducted in accordance with the PRISMA guidelines. Medline, Embase and Cochrane Central Register of Controlled Trials databases were searched using the following terms: penile cancer, penis, antineoplastic combined chemotherapy, taxane, docetaxel, paclitaxel, platinum, cisplatin, carboplatin. Studies were identified using preplanned eligibility criteria by 2 investigators (EA-E and JR). Data were extracted independently by EA-E and JR. Studies were weighted by study sample size and those comparing taxane-based chemotherapy were compared to non-taxane therapy using the Mann Whitney test. Results: The search identified 1929 publications and 40 were selected for further assessment. Of these, 8 met eligibility criteria (7 prospective and 1 retrospective). Three studies tested taxane combinations (docetaxel, cisplatin and 5FU [DCF] and paclitaxel, ifosfamide and cisplatin [TIP]). A total of 148 men with APC were treated with non-taxane regimens and 98 men received a taxane combination. Patient characteristics (age, ECOG status, stage, number of cycles) were comparable between the two groups. Partial response and overall response rates were significantly higher in the taxane versus the non-taxane group (35.7% vs. 24.2% p = 0.01 and 41.9% vs. 32.5% p = 0.007) respectively. Grade3/4 neutropenia was significantly higher in taxane group than non-taxane group (27.8% vs 19.4% p = 0.02). Median PFS and OS was numerically but not significantly higher in the taxane versus the non-taxane group (5.7 vs. 4.4 months, p = 0.45 and 12.1 vs 10 months, p = 0.48, respectively). Conclusions: Compared to non-taxane-based regimens, taxane combinations have higher response rates and may improve survival in APC. Hematologic toxicities are worse with taxane containing regimens. Taxane combinations should be the preferred regimen for suitable men with APC.

Patient education and psychosocial support to patients are important elements of comprehensive cancer care, but the needs of thyroid cancer survivors are not well understood.The published English-language quantitative literature on (i) unmet medical information and (ii) psychosocial support needs of thyroid cancer survivors was systematically reviewed. A librarian information specialist searched seven electronic databases and a hand search was conducted. Two reviewers independently screened citations from the electronic search and reviewed relevant full-text papers. There was consensus between reviewers on the included papers, and duplicate independent abstraction was performed. The results were summarized descriptively.A total of 1984 unique electronic citations were screened, and 51 full-text studies were reviewed (three from the hand search). Seven cross-sectional, single-arm, survey studies were included, containing data from 6215 thyroid cancer survivor respondents. The respective study sizes ranged from 57 to 2398 subjects. All of the studies had some methodological limitations. Unmet information needs were variable relating to the disease, diagnostic tests, treatments, and co-ordination of medical care. There were relatively high unmet information needs related to aftercare (especially long-term effects of the disease or its treatment and its management) and psychosocial concerns (including practical and financial matters). Psychosocial support needs were incompletely met. Patient information on complementary and alternative medicine was very limited.In conclusion, thyroid cancer survivors perceive many unmet information needs, and these needs extend to aftercare. Psychosocial information and supportive care needs may be insufficiently met in this population. More work is needed to improve knowledge translation and psychosocial support for thyroid cancer survivors.

Introduction Essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF) are a group of hematopoietic stem cell-derived clonal disorders collectively known as the classical, Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). Although MPN diagnoses are typically made in the sixth or seventh decade of life, approximately 20% of ET patients and 15% of PV patients are under the age of 40 years. Pregnancy with an MPN is associated with maternal thrombosis, hemorrhage and placental dysfunction leading to fetal growth restriction or loss. The aims of this systematic review were to determine the risk of maternal and fetal complications in pregnancy complicated by MPN and to quantify the benefit of commonly used interventions. Methods A systematic search was conducted using MEDLINE (1946 to July 2018), EMBASE (1947 to July 2018), Cochrane Database of Systematic Reviews (2005 to July 2018), CCRCT (inception to June 2018), and Epub Ahead of Print & Other Non-Indexed Citations (inception to July 2018). Bibliographic references were reviewed for additional studies. There were no date or language restrictions and the review was registered with PROSPERO (CRD42018090680). Studies were included if they reported on maternal or fetal outcomes of pregnancy in patients with an MPN. Case reports and series including fewer than 10 patients were excluded. Duplicate reports were excluded, with only the most recent or most informative included. Data were extracted independently by two investigators (D.M. and S.K.). The primary outcome was live birth. Secondary outcomes included fetal complications (e.g. intrauterine growth restriction) and maternal complications (e.g. pre-eclampsia, thrombosis, hemorrhage). Study quality was assessed using the Newcastle-Ottawa Scale. Analyses were performed using Open Meta-Analyst version 10.12 and Review Manager version 5.3. Results The search strategy resulted in 4191 records of which 22 met the inclusion criteria (Figure 1). The studies included a total of 779 women and 1226 pregnancies. Fifteen of the studies included patients with ET, 3 included patients with PV, and 4 included patients with any classical MPN. There were no studies of MF patients that met our inclusion criteria. Most of the studies were retrospective cohort studies (19) and 3 were prospective cohort studies. Among 1226 pregnancies, the live birth rate was 70%. Of 821 pregnancies with ET and 171 with PV, the live birth rate was 71% and 51%, respectively. The live birth rate was higher in patients with ET who received low dose aspirin during pregnancy than those managed with observation alone (OR 5.0; 95% CI 2.2 - 11.3; I226%; Figure 2). There was no further improvement with the addition of low molecular weight heparin (LMWH) to aspirin (OR 2.8; 95% CI 0.67 - 11.7; I20%). Interferon alpha (INF) during pregnancy was also associated with a higher live birth rate (OR 3.9; 95% CI 1.5 - 10.4; I22.5%; Figure 3). The presence of the JAK2 mutation resulted in a lower live birth rate (OR 0.58; 95% CI 0.4 - 0.9; I26%; Figure 4). Maternal events were unaffected by the addition of aspirin (OR 0.48; 95% CI 0.16 - 1.4; I20%) or INF (OR 0.1; 95% CI 0.01 - 1.5; I20%). Risk of bias assessment was performed using the Newcastle-Ottawa scale. Most studies included a representative cohort and follow up was generally adequate to at least 6 weeks postpartum. Only 3 studies included a control group. Conclusions The preliminary results of our systematic review determined that the live birth rate is lower in pregnant patients with MPN as compared to the general population. The chance of a successful pregnancy was higher in patients with ET than PV and the presence of the JAK2 mutation increased the risk of fetal loss. Patients who received low-dose aspirin during pregnancy had a 5-fold higher odds of a successful pregnancy than those managed with usual care and observation alone. Cytoreduction with INF improved the odds of live birth by nearly 4-fold. Maternal events were uncommon overall and no intervention was found to be beneficial. Our review is limited by generally small sample sizes and the retrospective nature of most studies. Additionally, given that the studies span up to 4 decades, our results may be affected by changing standards of care. Pregnancy in patients with MPN is uncommon and this is the only systematic review to determine the chance of successful pregnancy and quantify the benefit of commonly used interventions. Disclosures Maze: Novartis: Consultancy, Honoraria. Kazi:Shire: Other: Vonvendi was provided by Shire. Gupta:Novartis: Consultancy, Honoraria, Research Funding; Incyte: Research Funding.

Objective: Pulmonary hypertension (PH) is a rare but severe manifestation of systemic lupus erythematosus (SLE) that can ultimately result in death. The identification of factors that prognosticate survival in SLE-PH is necessary for appropriate monitoring, timing of therapeutics and lung transplantation. The primary objective of this study was to identify prognostic factors for survival in SLE-PH through review of the literature. The methodological quality of the prognostic studies was also evaluated .Methods: A systematic review of the literature was performed to identify studies evaluating prognostic factors for survival in SLE-PH. Medline, EMBASE, CINAHL, and Cochrane Central Registry of Controlled Trials (inception – week 2 2010) were searched. A standardized abstraction form was used by two independent reviewers to extract prognostic factors. Methodological quality was evaluated using a validated quality index. Results: Twenty-three observational studies from 375 citations were evaluated. Elevated mean pulmonary artery pressure, Raynaud’s phenomenon, thrombocytopenia, plexiform lesion, infection, thrombosis, pregnancy, pulmonary vasculitis and anticardiolipin antibodies were associated with decreased survival. Lupus disease activity, nephritis and central nervous system disease were not associated with survival. The sample sizes were small and methodological quality of the studies was variable. Conclusion: This study summarizes factors that may be associated with decreased survival in SLE-PH. The small sample sizes and variable methodological quality preclude definitive conclusions. This study provides the groundwork for further research using large cohorts.

40 Background: Continued smoking after a diagnosis of cancer negatively impacts cancer outcomes but the impact of tobacco on many innovative treatments has not yet been well established. Collecting and evaluating tobacco use in cancer clinical trials may advance understanding of the consequences of tobacco use on specific treatment modalities. We performed a systematic scoping review of the frequency of reporting and analysis of tobacco use in clinical trials run by cancer cooperative clinical trial groups. Methods: A comprehensive literature search was conducted to identify cancer cooperative group clinical trials published from January 2017 to October 2019 using Medline, Epub Ahead of Print and In-Process & Other Non-Indexed Citations, Embase, Cochrane Central Register of Controlled Trials using OvidSP. Eligible studies evaluated either systemic and/or radiation therapies, involved at least one cancer cooperative group, included > 100 adult patients and reported on at least one primary or secondary endpoint, which included overall survival (OS), disease/progression-free survival (DFS/PFS), response rates, toxicities/adverse events, or quality of life (QoL). Secondary analyses of previously published trials were excluded. Results: Among 14843 identified studies, 91 studies representing 90 trials met inclusion criteria. 24% were phase II trials, 2% phase II/III and 74% phase III. Trial start dates ranged from 1995-2015 with most (29%) between 2007-2008; median trial sample size was 406 (range: 100-4994); 86% involved systematic therapy, 35% involved radiation; 14% were lung and 5% were head and neck trials. 51% of trials had a curative intent, 33% were palliative and 16% involved hematologic cancers. 74 studies reported on OS, 73 DFS/PFS, and 88 toxicity/QoL. 19 studies reported baseline tobacco use information, while two reported collecting follow-up tobacco use. Of those collecting baseline tobacco use, only 7 reported any analysis of the impact of tobacco on clinical outcomes. There was significant heterogeneity in the reporting of baseline tobacco use: 5 reported never/ever status, 10 reported never/ex-smoker/current smoker status; 4 reported some measure of smoking intensity; none reported on verifying smoking status or second hand smoke exposure. Trials of tobacco related (lung and head and neck) cancers were more likely to report baseline tobacco use compared to non-tobacco related cancers (83% vs 6% p < 0.001). Conclusions: Few cancer cooperative group clinical trials report and analyze trial participants’ baseline tobacco use, and even fewer collect follow up information. Significant heterogeneity exists in reporting tobacco use. Routine standardized collection and reporting of tobacco use, both at baseline and follow up in clinical trials, should be implemented to enable investigators to evaluate the clinical impact of tobacco use on new cancer therapies.