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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.

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.

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.

PRISMA Extension for Scoping Reviews (PRISMA-ScR) (PDF 616 kb)

Figure S1. Medline Search Strategy (PDF 265 kb)

SMS Taxonomy (PDF 45 kb)

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]

Background Cancer survivors face a myriad of biopsychosocial consequences due to cancer and treatment that may be potentially mitigated through enabling their self-management skills and behaviors for managing illness. Unfortunately, the cancer system lags in its systematic provision of self-management support (SMS) in routine care, and it is unclear what implementation approaches or strategies work to embed SMS in the cancer context to inform health policy and administrator decision-making. Methods/design A comprehensive scoping review study of the literature will be conducted based on methods and steps identified by Arksey and O’Malley and experts in the field. Electronic searches will be conducted in multiple databases including CINAHL, CENTRAL, EMBASE, PsycINFO, MEDLINE, AMED, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE) (up to Issue 2, 2015), ISI Proceedings (Web of Science), PsychAbstracts, and Sociological Abstracts from January 1997 to November 5, 2018. Following the PRISMA-Extension for Scoping Reviews (PRISMA-ScR), two authors will independently screen all titles/abstracts to determine eligibility, data will be abstracted by one author and checked by a second author, and findings will be narratively summarized based on constructs of implementation in the Normalization Process Theory. Discussion This will be the first scoping review study to synthesize knowledge of implementation of SMS in the cancer care context and the implementation approaches and strategies on embedding in care. This information will be critical to inform health policy and knowledge end users about the necessary changes in care to embed SMS in practices and to stimulate future research. Electronic supplementary material The online version of this article (10.1186/s13643-019-0952-5) contains supplementary material, which is available to authorized users.

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.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.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.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.

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.

Supplemental material, sj-pdf-1-pmj-10.1177_02692163211015567 for Assessment tools for problematic opioid use in palliative care: A scoping review by Jenny Lau, Paolo Mazzotta, Rouhi Fazelzad, Suzanne Ryan, Alissa Tedesco, Andrew J. Smith, Abhimanyu Sud, Andrea D. Furlan and Camilla Zimmermann in Palliative Medicine