bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does the quality of patient-reported outcomes (PROs) assessment in randomized controlled trials (RCTs) differ across cancer types and over time? A pooled analysis of 610 RCTs published between 2004 and 2018.
Authors: Sparano Francesco , Aaronson Neil K , Sprangers Mirjam A.G. , Fayers Peter , Pusic Andrea , Kieffer Jacobien M , Rees Jonathan , Wan Chonghua , Pezold Mike , Fuzesi Sarah , Isharwal Sumit , Anota Amelie , Charton Emilie , Vignetti Marco , Cottone Francesco , Blazeby Jane M. , Efficace Fabio 
Published: May 2019

e18218 Background: PRO endpoints are increasingly being used in cancer RCTs. However, the PRO assessment in such trials often suffers from serious methodological shortcomings, and the results seldom impact on clinical policy or practice. Methods: We performed a systematic review to identify RCTs with a PRO endpoint in breast, colorectal, lung, prostate, gynaecological and bladder cancer. A checklist score for quality of PRO reporting (ranging between 0-100), based on that of the International Society for Quality of Life Research (ISOQOL) and the CONSORT PRO extension, was computed for each RCT. Analyses were also conducted by type of PRO endpoint (primary versus secondary) and year of publication (i.e. before and after the publication of the CONSORT PRO extension). Results: We identified 610 RCTs with a total of 323,482 patients. PROs were most frequently used in RCTs of breast (N = 176), followed by lung (N = 123), prostate (N = 108), colorectal (N = 103), gynaecological (N = 83) and bladder (N = 17) cancer. Quality of PRO reporting (mean score: 56.4) was highest in RCTs conducted in prostate cancer (PCa) (Table). Regardless of cancer type, quality of reporting was typically higher in RCTs where PROs were primary endpoints. Quality of reporting was higher for RCTs published after the CONSORT PRO Extension (2013), with the exception of RCTs conducted in PCa, where quality was stable over time. Conclusions: PRO reporting of RCTs conducted in PCa has better quality than in the other cancer sites that were reviewed. Regardless of cancer site, quality of PRO reporting has improved after the publication of the CONSORT PRO Extension. [Table: see text]
Pretreatment symptom prevalence in patients with myelodysplastic syndromes (MDS) across all disease risk categories: Analysis of 914 patients.
Authors: Efficace Fabio , Niscola Pasquale , Patriarca Andrea , Cottone Francesco , Palumbo Giuseppe A. , Breccia Massimo , Caocci Giovanni , Platzbecker Uwe , Specchia Giorgina , Stauder Reinhard , Fianchi Luana , Sanpaolo Grazia , Petranovic Duska , Frairia Chiara , Caers Jo , Santini Valeria , Bergamaschi Micaela , Capodanno Isabella , Di Renzo Nicola , Vignetti Marco 
Published: May 2019

e18220 Background: Whilst a substantial body of knowledge is available on the genetics and biology of MDS, very little is known on quality of life of these patients. We aimed to 1) examine patient-reported symptom prevalence in newly diagnosed MDS patients by disease risk at diagnosis; 2) investigate prevalence of other key symptoms by fatigue severity. Methods: Newly diagnosed MDS patients were recruited in an international prospective observational study from Nov. 2008 to Dec. 2018. As per standard practice, all patients were classified according to the International Prognostic Scoring System (IPSS) that identifies four risk subgroups of patients, i.e. low, intermediate-1 (i.e., lower risk, LR), intermediate-2, and high-risk (i.e., higher risk, HR). At baseline (i.e., pretreatment) patients also completed the validated FACIT-Fatigue scale and the EORTC QLQ-C30 questionnaires. Based on the FACIT-Fatigue median score, two groups were also identified: a lower and a higher fatigue group. Results: Out of 929 patients enrolled, 914 patients were available for current analysis of whom 496 with LR (median age of 74 years) and 418 with HR (median age of 72 years). Prevalence (i.e., with any level of concern) of symptoms by disease risk group is reported in Table. Patients with higher fatigue had a significantly higher prevalence of many other symptoms, such as pain (p < .001), dyspnea (p < .001), insomnia (p < .001), appetite loss (p < .001), diarrhea (p < .001) and constipation (p < .001) than patients with lower fatigue. To illustrate, moderate to severe dyspnea was reported by 38% of patients with higher fatigue and only by 5% of patients who reported lower fatigue. Conclusions: Pretreatment symptom prevalence in newly diagnosed MDS is high, and broadly similar in LR and HR patients. Regardless of disease severity at diagnosis, fatigue is associated with a substantial burden of other symptoms. [Table: see text]
A conundrum in cancer quality measurement: Performance on long-term survival reflects performance a long time ago.
Authors: Lipitz-Snyderman Allison , Curry Michael A. , Rubin David M. , Li Diane G. , Duck Elaine , Radzyner Mark H. , Bach Peter 
Published: May 2019

e18222 Background: Long term outcomes, such as five-year survival following cancer treatment, are widely accepted as important metrics of cancer care quality. But because they take years to accrue, they reflect the quality of care delivered in the past. The objective of this study was to delineate to what extent measures of long term outcomes related to cancer care could be reliably used to predict care quality in future periods. Methods: Taking advantage of FFS Medicare data from related studies, we assessed survival of cancer patients at one and four years by hospital for four separate index years 2006, 2011-2013. We assembled pairs of years across which we could compare risk adjusted outcomes separated by one year (2011 to 2012; 2012 to 2013), two years (2011 to 2013), and five through seven years comparing 2006 to 2011, 2012, or 2013 respectively. The outcome was risk adjusted mortality rates at the hospital level determined by dividing the observed number of deaths by an expected number, adjusting for age, and median income level of the zip code of residence. For each hospital and for every pair of analytic years we separately compared the correlation of one and four-year risk adjusted mortality using both Pearson and Spearman correlation statistics. A mixed effects model was fit to determine if size and year gap between measurements could explain possible differences in the correlation of hospital performance, while controlling for hospitals as a random effect. Results: There were 1,640 hospitals and more than 350,000 patients in each analysis year. Focusing on the correlation of the four year survival outcomes, the highest volume hospitals have significantly higher correlations compared to the other hospital categories (P < 0.001). The greater the elapsed time between measurement periods the lower the correlation. But in the mixed model analysis neither time elapsed between measurement periods (p = 0.51) nor the interaction between time elapsed and hospital volume (p = 0.95) were significant. Analyses of one-year outcomes produced similar findings. Conclusions: Performance on four-year survival outcomes of cancer patients was reasonably correlated for large volume hospitals, but less so for hospitals with lower volumes.
Effects of online education on the identification and management of immune-related adverse events over time.
Authors: Pender Lori Keys , Kadkhoda Haleh , Lucero Katie S. , Repetto Patti , Warren Charlotte , Gearhart Jacqueline , Weber Jeffrey S. 
Published: May 2019

e18224 Background: Immune checkpoint inhibitors (ICIs) are increasingly used in oncology care and produce a wide variety of immune-related adverse events (irAEs) that differ from toxicities of other systemic therapies. The objective of this study was to assess trends over time in oncologists’ knowledge, competence, and confidence managing irAEs. Methods: A series of online continuing medical education (CME) activities addressing irAEs was launched beginning in April 2014; 39 included multiple-choice knowledge/competence questions and a confidence question assessed on a 5-point Likert-type scale before and immediately after the activity. Activities that had at least 30 oncologists participate pre/post are included in this analysis. A pre-/post-assessment study design was used, and educational effect was assessed with chi-square tests. Analyses were conducted to examine trends in knowledge, competence, and confidence recognizing, identifying, and managing irAEs over four years on a quarterly basis. Weighted averages in each of the outcomes were calculated by quarter. Results: A total of 187,800 learners participated from April 2014-March 2018, including 96,177 physicians, of whom 25,127 were oncologists. The average increase pre- to post-test for 22 activities that asked a knowledge-based question was 18% (P < 0.001). The absolute increase from pre-test in 2014 (67%) to post-test in 2018 (87%) was 20 percentage points. For 16 activities with competence questions, the average increase from pre- to post-test was 8% (P < 0.001), and the absolute increase from pre-test in 2014 (39%) to post-test in 2017 (87%) was 48 percentage points. For 5 activities with a confidence question, the average increase from pre- to post-test was 8% (P < 0.05), and the mean rating pre-test in 2016 was 2.85 versus 3.53 post-test in 2018. Conclusions: Online CME is effective to improve oncologists’ knowledge, competence, and confidence managing irAEs; however, pre-test outcomes in 2018 demonstrate ongoing knowledge and competence gaps that should be addressed, and post-test confidence data indicate a persistent lack of confidence among oncologists even after participating in online CME.
Estimation of U.S. patients with cancer who may respond to cytotoxic chemotherapy.
Authors: Maldonado Edward , Parsons Scott , Chen Emerson Yu-sheng , Haslam Alyson , Prasad Vinay 
Published: May 2019

e18228 Background: Oncology drug development has shifted away from cytotoxic agents, while they remain widely used in clinical practice. We sought to estimate the proportion of U.S. patients with advanced or metastatic cancer who are eligible for and may respond to standard first-line cytotoxic chemotherapy alone based on National Comprehensive Cancer Network (NCCN) treatment guidelines. Methods: This retrospective review used publicly available annual mortality data from the American Cancer Society to estimate the number of patients who would have presented with advanced or metastatic disease. Published clinical trials of first-line cytotoxic-only regimens as advised by the NCCN were used to calculate overall response rates (complete plus partial response) for each cancer type. Chemotherapies in combination with immunotherapy or biologic agents were excluded. Mean response rate was used when there was more than one recommended regimen. The main outcome was to identify the proportion of patients with advanced or metastatic cancer who are eligible for and may respond to standard first-line cytotoxic chemotherapy regimens based on cancer type. Results: We identified 92 different cytotoxic chemotherapy regimens used in 25 cancer types. Among an estimated 609,640 cancer-related deaths in 2018, 479,823 (78.7%) would be eligible to receive standard first-line cytotoxic chemotherapy. We estimated 189,159 of 609,640 (31.0%) patients to achieve at least partial response. The median objective response rate was 48.6% (range 9.2%-90.6%). The following cancers had the highest response rate to cytotoxic chemotherapy: acute lymphoblastic leukemia (90.6%), acute myeloid leukemia (76.7%), and uterine cancer (75%). The following had the greatest number of patients who may respond to cytotoxic chemotherapy: lung cancer (60,234 of 609,640; 9.9%), colorectal cancer (23,138; 3.8%), and non-Hodgkin lymphoma (14,773; 2.4%). Conclusions: Given the large proportion of patients who may benefit from cytotoxic agents, drug development in this space may warrant continued interest in specific cancer types. Also, the regulatory approval of novel oncology drugs may justify head-to-head comparison against modern chemotherapy regimens.
Population health impact of genome-driven oncology by race and ethnicity.
Authors: Smieliauskas Fabrice , Sharma Hari , Catenacci Daniel V.T. , Huo Dezheng 
Published: May 2019

e18229 Background: The magnitude of clinical benefit from genome-driven oncology is the subject of controversy. Past estimates of the population health gains from genomic therapies have not explored differences by race and ethnicity (R/E) nor accounted for the lack of representativeness of commonly used tumor genomics databases. We assessed the attainable population health gains by R/E from cancer drugs with genomic biomarker indications for use. Methods: We used all patient (pt) samples of solid tumors from the AACR Project GENIE v3.0.0 tumor genomics data sharing initiative that met criteria for comprehensiveness of sequencing. We categorized biomarker-tumor site indications as actionable if FDA-approved or considered standard of care in the OncoKB Knowledge Base as of 1/25/19, and estimated actionability rates from genomic therapies. We modelled attainable median overall or progression free-survival gains for actionable pts and all pts from these therapies using results from registrational trials in pts with metastatic cancer. Analyses were performed for all pts and for Black, Asian, Hispanic, and non-Hispanic White R/E groups. To test for disparities in actionability rates (survival gains), we estimated logistic regression (least squares regression) models of having a clinically actionable gene abnormality (survival gains) regressed on minority R/E indicator variables and performed overall Chi-squared tests (F-tests) of whether the R/E coefficients were jointly equal to zero. All analyses were weighted to be representative of the U.S. cancer incident pt population by demographic and tumor site subgroup. Results: Data for 24,255 adult cancer patients met our criteria, including over 900 patients of each of the three minority R/E. Population-weighting showed that the Black and Hispanic pts were heavily underrepresented in the original sample. Weighted actionability rates were 18.2%, with disparities across R/E groups (p < 0.01) and Asians having the highest rates (24.0%). Median survival gains were 10.3 months among actionable pts (disparities test p < 0.10) and 1.9 months among all pts (disparities p < 0.01). Conclusions: Attainable population health gains from genome-guided oncology are modest with disparities across R/E groups.
Impact of dental insurance coverage on presentation, long-term outcomes, and symptom burden in locally advanced head and neck cancer.
Authors: Kacew Alec , Harris Ethan , Hanna Glenn J. , Haddad Robert I. , Tishler Roy B. , Schoenfeld Jonathan Daniel , Margalit Danielle Nina , Villa Alessandro , Limaye Sewanti Atul , Sanborn Matthew , Bae Ji Eun , Mahmood Umair , Cutler Jennifer , Criscitiello Shana , Huang Julian , Partridge Ann H. , Lorch Jochen H. 
Published: May 2019

e18230 Background: Medical insurance coverage is known to correlate with improved long-term (LT) outcomes in head and neck cancers (HNC) patients. However, associations with dental insurance coverage (DI) are not established. Methods: In 2012, we sent surveys to determine DI and LT symptom (Sx) burden (EORTC QLQ-30, National Health and Nutrition Examination Survey Oral Health, and Vanderbilt Head and Neck Sx Survey) to patients who had completed definitive chemoradiotherapy (sequential or concurrent) for locally advanced (LA) HNC at the Dana-Farber Cancer Institute from 2002-2011 (2013 ASCO annual meeting, abstract 9530). In 2019, we retrospectively collected demographic and clinical information from patient charts and publicly available records and correlated these data with 2012 survey data. We used Fisher’s exact tests for association of categorical variables and Student’s t-tests for continuous variables. We used univariate and multivariate Cox proportional hazard modeling for hazard ratios (HRs). Results: Of the 103 survey responders, 84% were male. Most had oropharyngeal (90, 88%) or unknown primary (9, 9%) and 52 (50%) tested positive for human papilloma virus-associated disease (40% not tested). 71 (69%) had DI, while 100 (98%) had medical health insurance. Subjects with DI were diagnosed (Dxed) at a younger age (53 vs. 59, p < 0.01). Stage at Dx did not vary by DI status (p = 0.27). At median follow-up of 10.4 years from Dx (range 2.0 -16.6), recurrence was not associated with DI status (6 (8%) for DI vs. 4 (13%) for no DI, p = 0.27, HR 0.55, 95% CI 0.15-1.93, p = 0.35). We identified 9 subjects (9%) who had died of any cause. Subjects with DI experienced lower mortality from all causes than those without (3% vs. 19%, p = 0.01) and longer median overall survival (OS) (range 4.3 - 16.6 years, HR 0.19, 95% CI 0.05-0.76, p = 0.02) on univariate analysis. The longer OS was not significant when controlling for age and stage at Dx (p = 0.12). DI was also associated with less frequent need for liquid supplements to maintain weight (p = 0.01). Conclusions: In our cohort, DI was associated with Dx at a younger age and longer OS, although future work should consider possible confounding factors such as differences in socioeconomic status. Our data highlight the need for further research to investigate the importance of DI in improving LT outcomes in HNC patients.
Flu vaccination rate of patients with severe immune-related adverse events.
Authors: Allen Ian Matthew , Murciano-Goroff Yonina Robbie , Zubiri Leyre , Li Qun , Hughes Michael Sang , Velimirovic Marko , Chu Jacqueline N. , Durbin Sienna , Klauer Matthew J , Awadalla Magid , Petrillo Laura A , Dougan Michael , Letourneau Alyssa R , Mansour Michael , Neilan Tomas G. , Cohen Justine Vanessa , Bardia Aditya , Reynolds Kerry Lynn 
Published: May 2019

e18234 Background: Infection with influenza in adults with cancer carries an increased risk of morbidity and mortality. Vaccination against seasonal influenza (Flu-V) can decrease the incidence of influenza, shorten its course, and reduce influenza-associated morbidity. Recent data has suggested that the administration of the Flu-V to patients on an ICI leads to an exaggerated inflammatory response and an increased risk of irAE. However, this trend was demonstrated in a small cohort of patients with lung cancer. Current recommendation for annual Flu-V in patients treated with ICI is unclear and literature about safety is limited. We compared rates of Flu-V for patients on ICI admitted with severe toxicity vs those patients on ICI who were admitted for reasons other than toxicity. We also evaluated rate of Flu-V among oncology patients who had received non-immunotherapy modalities. Methods: We retrospectively evaluated patients treated with ICI who were admitted to Massachusetts General Hospital from February 5, 2011- June 12, 2017. Patients received ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, or a combination in treatment of an advanced solid tumor malignancies including melanoma, NSCLC, SCCHN. Admissions due to irAE were confirmed by review of clinical, radiologic, and pathologic features. Flu-V status was determined by rigorous chart review. Nearest neighbor matching was used to create a control group of cancer patients treated with non-ICI modalities. Descriptive statistics compared rates and timing of Flu-V relative to admission. Statistical significance was determined using Fischer’s Exact Test, p < 0.05. Results: Of 540 patients on ICI, 28% were admitted for irAE, 72% had a non-irAE reason for admission. The rate of Flu-V in the flu season prior to admission for irAE group was lower than for non-irAE (18.5% vs 29.6%; p value = 0.01). There were no differences in vaccination rates within ≤30 days (2.7% vs 3.6%, p = 0.80), ≤90 days (4.0% vs 9.3%, p = 0.05), or ≤180 days of admission (11.9% vs 18.5%, p = 0.07). Flu-V rate overall in patients on ICI was 26.5%. In comparison, Flu-V rate in the nearest neighbor non-immunotherapy oncology patients was 67% (n = 101). Conclusions: Flu-V rates were much lower in patients treated with ICI compared to patients treated with non-ICI modalities. We did not see a higher rate of Flu-V in patients admitted with irAE compared to non-irAE which suggests that Flu-V and severe irAE may not be linked in clinical practice. Additional studies are needed, but Flu-V in patients on ICI holds potential to improve care.
Pregnancies in subjects on oncology clinical trials: Analysis from the Cancer Therapy Evaluation Program (CTEP) database.
Authors: Mittra Arjun , Murray James , Takebe Naoko , Chen Alice P. , Ivy S. Percy 
Published: May 2019

e18239 Background: The NCI Cancer Therapy Evaluation Program (CTEP) has developed guidance and reporting measures to balance inclusion of younger cancer patients on trials with minimizing potential risks. CTEP began mandating the use of 2 forms of contraception for all participants of child bearing potential starting in the early 2000s in trials of thalidomide in multiple myeloma. The development of oncology clinical trials using other known teratogens such as Hedgehog Inhibitors led to development of comprehensive guidance on enrolling women on clinical trials. In 2012, CTEP further updated its guidelines to develop a reporting system for pregnancies occurring on clinical trial. Methods: We performed a retrospective analysis of the CTEP Adverse Event Reporting System (AERS) to identify unanticipated pregnancies in subjects or their partners while on oncology clinical trials. Results: 33 events were identified between 2011 and 2018, including 21 female and 11 male. One female subject got pregnant twice on the same trial. In female subjects, there were 4 live births, 1 active pregnancy, 5 spontaneous abortions, 5 medical termination of pregnancy and 1 death of the mother due to cancer. Outcome of pregnancy was not reported for 6 female subjects. Of the live births: 3 received an immunotherapy checkpoint inhibitor, and 1 received trastuzumab. Of 5 spontaneous abortions: 3 received cytotoxic chemotherapy, one radiation and one trastuzumab. Of 12 male subjects whose partners got pregnant: 3 live births, 2 active pregnancy, no pregnancy loss. Outcome of pregnancy was not reported for 6 male subjects. Conclusions: Though uncommon, pregnancies on clinical trial still occur despite requiring subjects to use 2 effective forms of contraception. With the increasing number of younger subjects being included in clinical trials for cancer, information about pregnancy outcomes in patients being treated with experimental agents is scientifically valuable and important to collect from study subjects and their partners. Since not all anti-cancer agents are of equal teratogenic potential, it is vital that this data continues to be collected and reported, including long term follow up of the pregnancy and the health of the child.