bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between psoas muscle area (PMA) and density (PMD) with phase I oncology clinical trial outcomes.
Authors: Iyer Pritish , Whooley Peter , Handorf Elizabeth A. , Blau Matthew , Chertock Yana , Levin Laura , Hall Michael J. , Jain Rishi 
Published: May 2020

7007 Background: Malnutrition and cancer cachexia can lead to loss of muscle mass (sarcopenia) and are associated with poor outcomes. Muscle status can be evaluated by computed tomography (CT)-based radiographic measures, specifically at the L3 vertebrae where the psoas and other core muscles reside. We previously found that baseline malnutrition was associated with worse phase 1 clinical trial outcomes including increased toxicity and reduced survival (Jain et al. Oncologist, 2019). We sought to evaluate the relationship between muscle status and phase 1 trial outcomes. Methods: CT-based psoas muscle area (PMA) and psoas muscle density (PMD) were evaluated in 83 patients who enrolled in a phase 1 trial. We localized the L3 vertebral body on axial imaging and manually outlined the psoas muscle to calculate PMA (standardized to height) and PMD. Two reviewers independently conducted the analyses. We stratified patients by having a PMA or PMD above or below the group’s median. We evaluated for associations between PMA/PMD and the following clinical trial outcomes: rates of grade ≥ 3 toxicity, frequency of dose reductions/interruptions, hospitalizations, tumor response, duration on study (DOS), and overall survival (OS). We also evaluated for correlations between PMA/PMD and a validated measure of nutritional status, the PG-SGA. Chi-square analysis was used to determine statistical significance between groups. Kaplan-Meier curves were used to compare DOS and OS. Results: 83 patients were included (38 male, 45 female), with a median age of 60 (range 28-85). The most common cancer type was gastrointestinal (33%). Mean PMA was 2.89 cm2/m2 (range 1.41-5.72) and mean PMD 37.77 Hounsfield units (range 13.27-56.18). PMA above the median was associated with a reduced risk of grade ≥ 3 toxicity (32.5% vs 67.4%, p = 0.001). There was no association between PMD and grade ≥ 3 toxicity, or between PMA/PMD and other phase 1 trial outcomes. There was a significant correlation between nutritional status and PMA (r = -0.278, p = 0.01) but not PMD. Conclusions: PMA and PMD are readily available CT-based measures of muscle status. In oncology phase 1 clinical trial participants, lower baseline PMA was associated with a two-fold increased risk of grade ≥ 3 toxicity. Baseline PMA was moderately correlated with nutritional status which was previously shown to be associated with poor trial outcomes. More research is necessary to further understand the specific mechanisms by which nutritional status and muscle mass may influence toxicity risk in this population.
Association between Medicaid expansion status and metastatic disease at diagnosis in patients with melanoma.
Authors: Fabregas Jesus C. , Brant Jeannine M. 
Published: May 2020

7030 Background: The Affordable Care Act (ACA) expanded Medicaid coverage in 2010. It is unknown what impact the ACA expansion has had on a timely diagnosis for patients with melanoma. We hypothesize Medicaid ACA expansion has decreased the odds of being diagnosed with Stage IV melanoma. Methods: The National Cancer Database was queried. Analysis was restricted to patients diagnosed (dx’d) in or after 2010. Stage IV dx was the outcome variable. Predictors were dx’d at an already expanded ACA state (ES) or not (NES). Covariates were age, race, sex, education status, income, rural setting, and Charlson co-morbidity index. Univariate and Multivariate analyses were performed using logistic regression (table). The outcome model was adjusted using a generated Propensity Score as a continuous variable. An interaction term was used to evaluate for effect modification of ES on the association between race and Stage IV. Results: 219,475 patients diagnosed in 2010 or later were included. Median age was 62 years. By Univariate analysis, NES, age > = 65, black race, male sex, lower educational and income level, rural area, and a higher Charlson score were significantly associated with increased odds of being dx’d with Stage IV melanoma (all p < 0.001). By Multivariate Analysis, these associations persisted except for rural area and age. After adjusting for propensity score, ES patients were 9% less likely to be diagnosed with Stage IV melanoma as compared with NES patients (OR = 0.91 p < 0.001; 95% CI 0.867 – 0.959). ACA expansion status was an effect modifier on the association between race and late diagnosis (p = 0.004 for interaction term). For NES patients, black race had 3.26 odds (p < 0.001 95% CI 2.56 – 4.18) of being diagnosed with Stage IV as compared with white patients. The odds dropped to 1.76 (p 0.004; 95% CI 1.20 – 2.57) for ES patients. Conclusions: ES patients were less likely to be diagnosed with Stage IV melanoma as compared to NES patients. Medicaid expansion decreased the likelihood for black patients to be diagnosed with Stage IV as compared with whites. This suggests Medicaid expansion improves access to care and earlier diagnosis of melanoma and decreases racial gaps. [Table: see text]
Association of medical comorbidities and cardiovascular disease with toxicity and survival in patients receiving checkpoint inhibitor immunotherapy.
Authors: Johns Andrew , Wei Lai , Grogan Madison , Patel Sandipkumar , Li Mingjia , Husain Marium , Kendra Kari Lynn , Otterson Gregory Alan , Burkart Jarred Thomas , Owen Dwight Hall , Presley Carolyn J 
Published: May 2020

7039 Background: Checkpoint inhibitor immunotherapy (IO) is widely used to treat advanced cancer in pts. with medical comorbidities (MC), but the effect of MC on outcomes is poorly understood. Methods: We performed a single institution retrospective cohort study of pts. who received IO from 2011-2018. Immune-related adverse events (irAEs) were graded by Common Terminology for Adverse Events criteria, v4.0. MC were abstracted by query of ICD-10 codes corresponding to diagnoses in the Charlson Comorbidity Index (CCI) at any time prior to IO start. Modified CCI scores excluding points for cancer were calculated for each pt. Bivariate analysis with chi-squared statistics was used to describe characteristics and MC of pts. with vs. without irAEs. Overall survival (OS) was estimated by the Kaplan-Meier method (from start of first-line IO) and compared using the log-rank test. The association of CCI score and individual MC with irAEs and OS was tested with regression models adjusted for pt. characteristics. Results: Among 671 pts. with advanced cancer (39.6% melanoma; 21.8% non-small cell lung) treated with IO, median age 65 (IQR 55-74) years, the most common MC were COPD (24%) and diabetes (20%). 33.8% of pts. had CCI score ≥2. Neither CCI score nor any specific MC were associated with any grade or ≥G3 irAEs (P > 0.05). Increasing CCI score was significantly associated with decreased OS (P = 0.002). CHF (13.9 vs. 8.1 months, P = 0.008) and previous MI (14.2 vs. 10.1 months, P = 0.009) were associated with decreased median OS but did not remain significant in the regression model. Among pts. without cardiovascular disease (CVD), pts. with ≥G3 irAEs had longer OS than pts. with no ≥G3 irAEs (P < 0.001). This OS benefit for ≥G3 irAEs was not seen in pts. with CVD (P = 0.94). See table for adjusted HR. Conclusions: Risk for irAEs does not appear to be impacted by MC. Pts. with MC have shorter OS, but no specific MC are associated with OS after adjustment for pt. characteristics. OS is significantly increased among pts. without CVD who experience ≥G3 irAEs. CVD may be an important predictor of OS in pts. with irAEs and should be evaluated in patients receiving IO. [Table: see text]
Nurse, oncologist, and patient impressions of electronic symptom monitoring via patient-reported outcomes in community oncology practices: Qualitative results from the U.S. national PRO-TECT trial (AFT-39, NCT03249090).
Authors: Basch Ethan M. , Teal Randall , Dueck Amylou C. , Jansen Jennifer , Henson Sydney , Vu Maihan , Carda-Auten Jessica , Carr Philip M , Wang Mian , Bennett Antonia Vickery , Stover Angela M. 
Published: May 2020

7044 Background: There is growing interest to implement electronic patient-reported outcomes in oncology practices for symptom monitoring. It is not well known what nurse, physician, and patient impressions of benefits, acceptability, and challenges are in routine care use. Methods: PRO-TECT is an ongoing U.S. national trial including 26 community oncology practices across 15 states that implemented PRO symptom monitoring [NCT03249090]. Patients complete weekly PROs between visits, nurses receive alerts for severe/worsening symptoms, and oncologists review PROs at office visits. Interviews were conducted with 147 stakeholders including nurses (N = 46), oncologists (N = 27), data managers (N = 15), and patients (N = 59). Each stakeholder group had different interview guides with overlapping topics to explore experiences with the PRO system. Interviews lasted 15-60 minutes, were digitally recorded, transcribed, and entered into a qualitative analysis software program. A codebook was developed from the research questions, interview guides, and discussions with the project team. Standardized coding methods were applied, with transcripts double coded for thematic analysis. Feedback surveys were also completed by nurses (N = 57), oncologists (N = 38), and patients (N = 435). Results: Key benefits perceived across stakeholder groups included increased patient self-awareness of symptoms; improved direct communication of patients with care teams; more open and honest conveying of symptom experiences; ability to track symptoms over time; and increased involvement of patients in their own care. Most stakeholders felt PRO symptom monitoring had a positive impact on quality of care delivery, and believed benefits of PROs outweighed necessary staff efforts. Challenges included additional work by nurses to review and respond to alerts, staff turnover requiring retraining, and limited time of oncologists. In the survey, 39/56 (70%) nurses felt the PRO system improved quality of care; 27/33 (82%) oncologists noted PROs were useful for team discussions and care delivery; and 320/434 (74%) patients agreed that weekly PRO reporting improved discussions with their care team. Conclusions: Clinicians and patients perceived weekly PRO symptom monitoring between visits to be valuable despite added staff effort. Results of additional analyses are forthcoming. Clinical trial information: NCT03249090 .
Inclusion of economic outcomes in NCI grants: A portfolio analysis.
Authors: Halpern Michael T. , McCarthy Sharon , Tuovinen Priyanga 
Published: May 2020

7047 Background: While new interventions have improved cancer screening, treatment, and survivorship, the costs and other economic impacts of interventions may affect their uptake and availability. It is unknown what proportion of recently-funded National Cancer Institute (NCI) grants include economic outcomes. Methods: We used the NIH Query/View/Report (QVR) System to determine the number of competitive grants funded by NCI 2015-2020 that included economic outcomes. Grants were identified using the NIH Research, Condition, and Disease Categorization (RCDC) category “Cost Effectiveness Research”; 19 RCDC terms/concepts related to economic analyses; and 18 economic phrases searched for in grant titles, abstracts, and specific aims. The specific aims and abstracts of all grants meeting any of these search criteria were reviewed by an NCI scientist to ensure the presence of economic study outcomes. Results: Among over 13,700 competitive grants awarded by NCI 2015-2020, the search identified 149 grants; following abstract/specific aims review, 102 of these grants (0.74% of all grants) included an economic outcome. Most (69 of 102, 67.6%) included cost-effectiveness analysis; 24 included other cost analyses, 7 assessed financial hardship or similar outcomes, and 2 focused on developing economic methods. Among RCDC terms, more than half (53) listed modeling (9 listing Cancer Intervention and Surveillance Modeling Network), 24 randomized controlled trials, 15 QALYs, 11 implementation science, 3 willingness to pay. The most common cancer sites listed were breast (28), lung (23), cervical (19), and colorectal (17) cancer. Almost half (48) mentioned screening and 24 cancer prevention. Risk factors listed included 28 for smoking, 18 HPV, 8 HIV, 8 physical activity, 6 obesity, 4 nutrition. Ten listed treatment efficacy, 6 chemotherapy, 4 radiation therapy, 3 hormone therapy, and 1 chemoradiation. “Treatment as usual” was listed by 16, symptom management 4, and telehealth 4. Survivors were listed for 15, caregivers 3, health disparity 18, rural 15, young adult 4. The majority of grant mechanisms were R01 (76, 74.5%); 3 were R21/R03, 4 other R mechanisms, 7 K awards, 6 U grants, 6 P, F, or L grants. Conclusions: While this search may not have identified all funded NCI grants over the past 5 years involving economic analyses, we found that less than 1% included economic outcomes. Recommendations to assist NCI in supporting health economics research focused on cancer across the entire care spectrum should be considered.
Comparative effectiveness of proton versus photon chemoradiotherapy for patients with private insurance.
Authors: Baumann Brian Christopher , Mitra Nandita , Harton Joanna , Xiao Ying , Wojcieszynski Andrzej , Gabriel Peter Edward , Zhong Haoyu , Geng Huaizhi , Doucette Abigail , Wei Jenny J. , O'Dwyer Peter J. , Bekelman Justin E. , Metz James M. 
Published: May 2020

7049 Background: Proton therapy may increase the tolerability/efficacy of concurrent chemoradiotherapy (CRT) but is controversial & generally not covered by private insurers. There is little data on the comparative effectiveness (CE) of proton vs photon CRT among private insurance pts to guide payers on proton coverage policies. Methods: We conducted a CE study of adult non-metastatic cancer pts with private insurance treated with curative-intent proton vs photon CRT from 2011-2016 at Penn. The choice of radiation modality was heavily influenced by the insurer’s proton coverage policy. Data on adverse events (AEs) & survival were gathered prospectively using standardized templates. Primary endpoint was 90-day AEs associated with unplanned hospitalizations (CTCAEv4 grade ≥3 AEs). Secondary endpoints included 90-day grade ≥2 AEs, decline in ECOG performance status (PS) during treatment, disease-free survival (DFS) & overall survival (OS). Modified Poisson regression models with inverse propensity score weighting were used for adverse event outcomes. Weighted Cox proportional hazards models were used for survival outcomes. Propensity scores were estimated using an ensemble machine-learning approach. P<0.01 was significant. Results: 920 pts were included (178 proton/742 photon), with H&N(25 proton/296 photon); CNS(44/128); lung(41/120); upper GI(34/78) & lower GI/GYN(34/120). Median age was 57. Race, comorbidity score, BMI, baseline AEs & baseline PS were similar (p>0.05 for all). 11.2% of proton pts had grade ≥3 AE’s vs 26.8% of photon pts. On propensity score weighted-analyses, proton CRT was associated with significantly lower relative risk (RR) of 90-day grade ≥3 AEs (RR 0.51, 95%CI 0.32-0.81, p<0.01). 90-day grade ≥2 AE’s (RR 0.91, 95%CI 0.83-0.99, p=0.03); decline in PS (RR 0.85, 95%CI 0.70-1.04, p=0.11); DFS (HR 0.64, 95%CI 0.27-1.52, p=0.31) & OS (HR 0.53, 95%CI 0.18-1.52, p=0.24) favored protons. Sensitivity analysis showed that a substantial imbalance in an unmeasured confounder would be needed to alter the significance of the primary outcome. Proton accepting insurance status was not associated with a difference in 90-day grade ≥3 AE’s (RR 1.02, 95%CI 0.95-1.10, p=0.54) for pts treated with photon CRT (608 with non-proton accepting insurance & 134 with proton-accepting insurance). Conclusions: In adults with private insurance, proton CRT was associated with significantly reduced acute grade ≥3 AE’s with similar DFS & OS. Proton-accepting insurance status was not associated with better health outcomes when adjusting for RT modality.
Rates of adherence to bone health guidelines for women with breast cancer treated with anti-estrogen therapy.
Authors: Elliott Leighton Andrew , Vogel Victor G. 
Published: May 2020

7051 Background: Long-term use of aromatase inhibitor (AI) therapy has been shown to decrease bone mineral density (BMD) and is associated with at least twice the fracture risk when compared to an age-matched healthy population. AI’s are a common treatment in hormone receptor-positive breast cancer for post-menopausal women. Similarly, tamoxifen has been shown to decrease BMD in premenopausal women. As a result, the National Comprehensive Cancer Network (NCCN) recommends BMD screening for women being treated with anti-estrogen therapy (AET), typically via Dual-energy X-ray absorptiometry (DEXA) scan. Previous studies have shown poor adherence to BMD screening with AI therapy, but no known study has evaluated compliance with tamoxifen therapy. Methods: We evaluated a retrospective cohort (December 2015 – July 2019) of all women with a breast cancer diagnosis initiating AET using data from the electronic health records of patients throughout a rural integrated health system. We assessed non-adherence to baseline and annual BMD screening using descriptive statistics along with preliminary data regarding fractures associated with AET therapy. Results: A total of 3,693 health records of women with a breast cancer diagnosis and documented prescription for AET were evaluated. In the year before AET initiation, 16% of women received BMD screening. Overall, 1,189 women treated with AET had a DEXA scan ordered at any point after drug initiation: 37% for AI’s and 12% for tamoxifen. Of those treated with AI, 84% had no DEXA ordered within 12 months of starting drug after a minimum of 9 months of continuous use; this value was 96% for tamoxifen use. Patients complied with the ordered DEXA scan within the first year 81% of the time. Repeat DEXA scans were ordered 34% of the time, and patient compliance decreased to 55%. There was no significant difference in the number of patient co-morbidities between patients who did and did not have a DEXA scan ordered. After starting an AI, 131 fractures were documented; 44% occurred within the first year following starting drug treatment with an average of 5 months from drug start to diagnosis. Conclusions: A significant proportion of breast cancer patients treated with AET did not receive guideline-recommended BMD screening. These findings should raise awareness of the importance of BMD screening by responsible providers, including oncologists, primary care physicians, care managers and insurance companies in order to decrease avoidable morbidity.
Factors associated with change in the magnitude of clinical benefit of anti-cancer drugs in the post-marketing period.
Authors: Bujosa Rodríguez Aida , Molto Consolacion , Hwang Thomas J , Vokinger Kerstin Noëlle , Tapia Jose Carlos , Gich Saladich Ignasi J. , Templeton Arnoud J. , Barnadas Agusti , Amir Eitan , Tibau Ariadna 
Published: May 2020

7052 Background: Initial drug approval is often based on surrogate endpoints. Definitive outcomes like Overall Survival (OS) or Quality of life (QoL) may not be available. Here, we evaluate changes in the magnitude of clinical benefit using the American Society of Clinical Oncology Value Framework (ASCO-VF) and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) comparing the time of approval to the most recent available data for cancer drugs approved by the US Food and Drug Administration (FDA) between 2006 and 2015. Methods: We examined data on trials supporting FDA accelerated (AA) and regular (RA) cancer drug approvals between January 2006 and December 2015. We performed a systematic search of Pubmed and ClinicalTrials.gov to identify updated OS and/or QoL data, with follow up through April 2019. For AA drugs we analysed initial and confirmatory trials as follow-up. ASCO-VF and ESMO-MCBS grades were applied for trials at approval and after marketing. We explored variables associated with improved clinical benefit scores using multivariable logistic regression. Results: We identified 102 trials supporting the approval of 59 drugs for 96 solid tumour indications. Of these indications, 22 (23%) were granted AA and 21 (95%) were converted to RA. At time of approval, 38% of trials showed improved OS and 17% improved QoL. Substantial clinical benefit was observed in 26% of initial approval trials using ESMO-MCSB and in 34% using ASCO-VF. After a median post-marketing period of 3.3 years, updated results changed substantial clinical benefit in 20 trials with ESMO-MCBS (19 upgrades, 1 downgrade) and in 23 trials using ASCO-VF (19 upgrades, 4 downgrades). For 25% of trials no updated information was found. In the palliative setting, multivariable analysis showed association between improved ASCO-VF scores and initial approvals based on single-arm trials (OR 9.21, 95%CI 1.36-62.29, P=0.023), drugs with companion diagnostics (OR 4.95, 95%CI 1.01-24.22, P=0.049) and second or later lines (OR 7.80, 95%CI 1.35-45.02, P=0.022) while for ESMO-MCBS, drugs with companion diagnostics (OR 6.86, 95%CI 1.82-25.86, P=0.004) and immunotherapy drugs (OR 6.42, 95%CI 1.27-32.59, P=0.025) were associated with greater clinical benefit. Conclusions: Drugs with companion diagnostic tests, immunotherapy as well as approved based on single-arm trials were associated with increased clinical benefit after marketing approval. For a quarter of trials there were no updated data in the post-marketing period.