bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy, safety, and immune priming effect of tazemetostat in patients with epithelioid sarcoma.
Authors: Gounder Mrinal M. , Stacchiotti Silvia , Schoffski Patrick , Cote Gregory Michael , Villalobos Victor Manuel , Jahan Thierry Marie , Chen Tom Wei-Wu , Ratan Ravin , Gupta Abha A. , Dileo Palma , Agulnik Mark , Italiano Antoine , Attia Steven , Mir Olivier , Pressey Joseph Gerald , Sierra Laura , Lingaraj Trupti , Yang Jay , Agarwal Shefali , Jones Robin L. 
Published: May 2020

11564 Background: Epithelioid sarcoma (ES) is a rare, aggressive soft tissue sarcoma characterized by loss of inhibitor of integrase 1 (INI1), allowing enhancer of zeste homologue 2 (EZH2) to repress cell differentiation and promote tumorigenesis. Tazemetostat (TAZ) is a selective inhibitor of EZH2 approved by the FDA for treatment of patients (pts) aged ≥16 years with metastatic or locally advanced ES ineligible for complete resection. Methods: This open-label, multicenter, multi-cohort phase 2 study (NCT02601950) evaluated safety and efficacy of TAZ in pts with INI1-negative tumors. ES pts were enrolled in Cohorts 5 and 6; pts in Cohort 6 underwent mandatory pre-dose (at screening) and post-dose biopsies (at Day 1 of cycle 2). Herein, we report the interim efficacy and safety data from Cohort 6. Results: As of July 31 2019, 44 pts were enrolled into Cohort 6 and treated with TAZ 800 mg BID. The objective response rate (ORR) was 11.4%; 4 pts (9.1%) had a partial response and 1 pt (2.3%) had a complete response (Table). Another 17 pts (38.6%) had stable disease (SD). 18 pts had progressive disease; 13 of these pts remained on study beyond progression. Progression-free survival (PFS) and overall survival (OS) at 56 weeks were 19.4% and 59.4%, respectively. In a pooled posthoc analysis of 106 ES pts from Cohorts 5 (n = 62), and 6, ORR was 13.2%. Grade 3–4 adverse events (AEs) were reported in 16 pts (36.4%), most commonly anemia (6.8%; n = 3) and tumor pain (6.8%; n = 3). 3 pts (6.8%) experienced grade 3–4 treatment-related AEs. One pt discontinued study drug and there were no treatment-emergent dose reductions or treatment-related deaths. These safety data from Cohort 6 are consistent with previously reported data from Cohort 5. 19 paired biopsies were included for translational endpoint analyses. Preliminary RNA seq and pathway analyses are currently ongoing and updated data, including additional biomarker data will be presented. Conclusions: Consistent with previously reported data from the completed Cohort 5, TAZ demonstrated clinically meaningful, durable, single agent activity in ES pts. Efficacy data from Cohort 6 continue to mature with 8 patients still on treatment. TAZ was well tolerated with a low incidence of treatment related AEs. Clinical trial information: NCT02601950 . [Table: see text]
Effect of early integration of specialized palliative care into standard oncologic treatment on the quality of life of patients with advanced head and neck cancers: A phase III randomized controlled trial.
Authors: Singhai Pankaj , Patil Vijay Maruti , Muckaden Mary Ann , Deodhar Jayita , Salins Naveen , Noronha Vanita , Joshi Amit , Menon Nandini Sharrel , Khake Ashwini , Dhumal Sachin Babanrao , Prabhash Kumar 
Published: May 2020

12013 Background: Early palliative care is an important aspect of palliative treatment but has never been evaluated in head and neck cancer. Hence we performed this study. Methods: This was an open-label phase 3 randomised study which enrolled adult patients with squamous cell carcinoma of the head and neck region which warranted palliative systemic therapy. They were 1:1 allocated to either systemic therapy with (EPC arm) or without the addition of early palliative care service (STD arm). Patients were administered the Edmonton Symptom Assessment Scale (ESAS-r) and FACIT HN questionnaire at baseline and 4 weekly thereafter for 12 weeks. The primary endpoint was change in the quality of life (QOL) measured using FACIT HN 12 weeks after randomization. The secondary endpoints were changed in symptom burden at 12 weeks in ESAS-r and overall survival. A repeated-measures analysis of covariance (ANCOVA) was performed to examine the effects of arm and stratum on change in QOL (or symptom score), after controlling for baseline score. Results: Ninety patients were randomised in each arm between 1st June 2016 to 14th August 2017. The compliance with the questionnaires was 100% at baseline. In EPC arm the 70 patients were alive at 3 months and 67 (95.7%) completed the FACIT HN and 64 (91.4%) completed ESAS-r questionnaires. While in the STD arm out of 69 alive the corresponding figures were 61(88.4%) and 59 (85.5%) respectively. There was no statistical difference in change in QOL scores and ΔESAS-r at 12 weeks between the 2 arms (Table). The median overall survival was similar between the 2 arms. (Hazard ratio for death-1.006 (95%CI 0.7347-1.346)). Conclusion: In this phase 3 study, integration of early palliative care in head and neck cancer patients did not result in improvement in the quality of life scores, symptom scores or overall survival. Clinical trial information: CTRI/2016/03/006693 . [Table: see text]
Prevalence and temporal trends of prescription drug use in cancer survivors: A population study, 2001 to 2016.
Authors: Liu Elisa , Kurz Sylvia Christine , Ahn Jiyoung , Sulman Erik P. 
Published: May 2020

12023 Background: The burden of prescription drug use is higher in cancer survivors than the general population. We examined the prevalence and temporal trends of prescription drug use among cancer survivors, with an emphasis on central nervous system (CNS) active medications used to manage long-term cancer sequelae. Methods: Adult respondents with (n=3207) and without (n=40,440) a prior cancer diagnosis from 8 cycles (2001-2016) of the National Health and Nutritional Examinational Survey (NHANES) were evaluated for prescription drug usage. Cross-sectional analyses and temporal trends across cycles were evaluated and weighted to represent the US adult population. Results: Cancer survivors report higher rates of prescription drug usage (85.1% vs 54.3%, p<0.001, and 75.8%, p<0.001) and polypharmacy (27.8% vs 10.7%, p<0.001, and 22.7%, p<0.001) than both unadjusted and age-adjusted controls. Younger survivors report greater usage of CNS (36.8% vs 13.1%, p<0.001), psychotherapeutic (18.4% vs 7.7%, p<0.001), hormonal agents (19.1% vs 10.1%, p=0.003), and gastrointestinal (10.7% vs 4.7%, p=0.02) than controls, while differences are attenuated in older cohorts. Among broad drug categories, the usage of cardiovascular (p-trend<0.001), metabolic (p-trend<0.001), and immunologic agents (p-trend=0.01) has increased. Among CNS active subclasses, the usage of anticonvulsants (p-trend<0.001), anxiolytics (p-trend =0.02), narcotics (p-trend=0.02) and GABA analogs (p-trend<0.001) has increased. When comparing respondents with and without a history of cancer, the increased usage of anti-depressant prescription medications (18.3% vs 1.5% p<0.001), including SSRIs (11.2% vs 1.0%, p<0.001), SSNRIs (3.5% vs 0.3%, p<0.001), tricyclics (2.8% vs 0.1%, p<0.001), among cancer survivors was disproportionate compared to the increased proportion of positive depression screens (9.2% vs 7.0%, p=0.006). Conclusions: Cancer survivors report higher prescription drug use for both chronic conditions and late effects of cancer. The usage of CNS active medications, many of which are used on and off label for their pain management properties, has increased. The higher rates of pharmaceutical use may result in unanticipated long-term toxicities and financial burdens.
The adoption of immune checkpoint inhibitors and patterns of care at the end of life.
Authors: Riaz Fauzia , Gan Geliang , Li Fangyong , Davidoff Amy J. , Adelson Kerin B. , Presley Carolyn J , Adamson Blythe J.S. , Shaw Pooja , Parikh Ravi Bharat , Mamtani Ronac , Gross Cary Philip 
Published: May 2020

12027 Background: As immune checkpoint inhibitors (ICIs) have transformed the care of patients with cancer, it is unclear whether treatment at end of life (EOL) has changed. Because aggressive therapy at EOL is associated with increased costs and patient distress, we explored the association between the FDA approvals of ICIs and treatment patterns at EOL. Methods: We conducted a retrospective, observational study using patient-level data from the Flatiron health EHR-derived de-identified database. Patients had advanced melanoma, non-small cell lung cancer (NSCLC) (cancer types with an ICI indication) or microsatellite stable (MSS) colon cancer (a cancer type without an ICI indication) and died between 2013 and 2017. We calculated annual proportions of decedents who received systemic cancer therapy in the final 30 days of life and used logistic regression to model the association between the post-ICI Federal Drug Administration (FDA) approval time period and use of systemic therapy at EOL, adjusting for patient characteristics. We also assessed the use of chemotherapy or targeted/biologic therapies at EOL, before and after FDA approval of ICIs using Pearson Chi Square test. Results: There was an increase in use of EOL systemic cancer therapy in the post-ICI approval period for both melanoma (33.9% to 43.2%, p-value < 0.001) and NSCLC (37.4% to 40.3%, p-value < 0.001). In contrast, the control group of decedents with MSS colon cancer demonstrated no significant increase in use of systemic therapy at EOL. After controlling for patient characteristics, there was a significantly higher odds of receiving systemic treatment at EOL in the post-ICI time period compared to the pre-ICI time period in melanoma (OR 1.42, 95% CI 1.09-1.86, p-value < 0.001) and NSCLC (OR 1.13, 95% CI 1.06-1.20, p value < 0.001), with no significant difference in receipt of systemic therapy in patients with MSS colon cancer. After FDA approval of ICIs, patients with NSCLC and melanoma had a decrease in the use of chemotherapy, with a concomitant increase in use of ICIs at EOL. Decedents with MSS colon cancer did not have a statistically significant change in use of chemotherapy or targeted/biologic therapies during the study period. Conclusions: The adoption of ICIs was associated with a substantive increase in the use of systemic therapy at EOL in melanoma, and a smaller yet significant increase in NSCLC.
Abbreviated geriatric assessment (GA) in new oncology patients and its association with early death.
Authors: Maranzano Michael , Neerukonda Anu Radha , Wallace James Alfred , Dale William , Polite Blase N. , Chow Selina Lai-ming 
Published: May 2020

12035 Background: The ASCO 2018 Geriatric Oncology Guidelines support the broad application of GA to risk-stratify patients age ≥65 undergoing cancer-directed therapy. Despite this, GA has not been widely adopted due largely to perceived time and resource constraints. We administered an abbreviated GA by medical assistants (MAs) in an outpatient oncology clinic to explore its feasibility and correlation with adverse events. Methods: This is a single-institution, retrospective study of adults establishing oncology care at an academic medical center from 11/2016-4/2017. MAs completed an abbreviated GA of well-validated tests. Cognitive function was screened by the Mini-Cog (score < 4) and physical function by the Five Times Sit-to-Stand Test (FTSST ≥ 15 seconds). Patient-reported Outcomes (PRO) screened for malnutrition by the Malnutrition Screening Test (MST ≥ 2), for vulnerability by Vulnerable Elders Survey (VES-13 ≥ 3) and for depression by Patient Health Questionnaire-4 (PHQ-4 > 2). The first result within 3 months of the initial visit was used for analysis. ED visits, inpatient admissions and early death, defined as within the first 6 months from the initial visit, were collected from the electronic medical record. GA results and baseline characteristics were modeled for these events using univariate logistic regression. Multivariable regression was performed when univariate regression revealed at least 2 factors with p< 0.1. Results: New patients 65+ years (n=304, median age 72) established care in our practice during this six-month period. Nearly all patients (n=285, 94%) completed at least one GA test. Fewer patients completed the Mini-Cog and FTSST (60% completed) compared to the PRO screenings (83-90% completed). Those with any positive GA screening test were nearly 3 times as likely to die within 6 months of their initial outpatient visit compared with those with no deficits (OR 2.95, 95% CI 1.11-9.30). Those with FTSST ≥ 15 sec or unable to complete were more likely to have an ED visit within 6 months (OR 2.40, 95%CI 1.04-5.46).No other individual screening test had a statistically significant association with adverse events. Conclusions: An abbreviated version of GA completed by MAs can be incorporated into new oncology patient visits for all older adults, and those with any abnormalities on screening tests had a higher likelihood of early death. [Table: see text]
Communication about comorbidities among 527 older patients with advanced cancer and their oncologists and caregivers: A multisite cluster-randomized controlled trial.
Authors: Kleckner Amber , Gilmore Nikesha , Belcher Elizabeth , Magnuson Allison , Dunne Richard Francis , Kleckner Ian , Xu Huiwen , Culakova Eva , Wells Megan , Vogelzang Nicholas J. , Dib Elie G. , Targia Valerie , Peppone Luke Joseph , Mustian Karen Michelle , Mohile Supriya Gupta 
Published: May 2020

12040 Background: Older patients with advanced cancer often have comorbidities that increase the risk of toxicity from neoplastic therapy but are not always considered in treatment planning. We assessed the utility of a geriatric assessment (GA) intervention to increase the number and quality of discussions about comorbidities among oncologists, older patients, and caregivers. Methods: This multi-site trial enrolled patients who were ≥70 years, had advanced solid tumors or lymphoma, had ≥1 GA impairment, and who were considering or receiving cancer treatment. All patients received the GA and completed an Older Americans Resources and Services Comorbidity survey, which evaluated 15 conditions and interference with activities (clinical impairment = ≥3 comorbidities or ≥1 highly interfering). Oncology practices were randomized to intervention (GA with a summary with management recommendations provided to oncologists) or usual care (GA only). The clinic visit after GA was audio-recorded, transcribed, and coded for GA topics including comorbidity. Generalized linear mixed models adjusting for site (random effect) were used to assess the effect of the intervention. Results: Patients (n=527 evaluable, 76.6±5.2 years, 49% female) and oncologists (n=131, 63 in intervention) were enrolled from 31 sites. In total, 94.5% of patients had ≥1 comorbidity with an average of 3.2±1.9; 64% were clinically impaired by comorbidity (p=0.76 between arms). The intervention arm had twice the number of conversations about comorbidities (1.02 vs. 0.52 conversations per patient, difference 0.50, 95% CI 0.18-0.81, p=0.004) and conversations were more likely to be initiated by the oncologist (p<0.001, Table). Moreover, among patients who had conversations about comorbidities, more patients in the intervention arm had discussions specifically addressing comorbidities (e.g., cancer treatment modification, communication with the primary care physician; 24.3% vs. 7.5%, p=0.003). Conclusions: Providing oncologists with a GA summary and recommendations encouraged them to engage in more discussions about their patients’ comorbidities with the goal of addressing interactions between comorbidities, cancer, and its treatments. Funds: PCORI CD4634, NCI UG1CA189961 Clinical trial information: NCT02107443 . [Table: see text]
Gait speed and recommended treatment intensity among older adults with blood cancers.
Authors: Hantel Andrew , Odejide Oreofe O , Luskin Marlise Rachel , Sperling Adam Samuel , Hshieh Tammy , DuMontier Clark , Chen Richard , Soiffer Robert , Driver Jane A. , Abel Gregory A. 
Published: May 2020

12041 Background: Gait speed identifies frailty and predicts survival among older adults with hematologic malignancies (Liu, Blood, 2019). It is not known if gait speed correlates with the intensity of oncologists’ recommended treatment in this population. Methods: From 2/2015-11/2019, patients ≥75 years presenting for an initial hematologic malignancy consultation at the Dana-Farber Cancer Institute were approached for a screening frailty assessment including a 4-meter gait speed test, reported as <0.4, 0.4-0.6, 0.6-0.8, or >0.8 meters/second (m/s). Faster gait speed is associated with less frailty and predicts better survival. Gait speed was not reported to the oncologist. Treatment recommendations were categorized into standard, reduced, or no therapy based on NCCN guidelines, as applicable. Gait/treatment intensity “mismatches” were characterized as patients with lowest quartile gait speed recommended standard intensity and highest quartile not recommended standard intensity. Multivariable regression was performed to assess if gait speed predicted treatment intensity (controlling for age, sex, ECOG performance status [PS], and disease type). Results: Of 786 patients enrolled, 408 required active treatment where NCCN guidelines vary by fitness. Mismatches were seen in 26.7% of patients (Table: column percentages with 95% CI, mismatches starred): 10 (21.3%) with lowest quartile gait speed recommended standard intensity and 99 (55.0%) with highest quartile recommended reduced or no therapy. In multivariable analysis, PS was predictive of no therapy as compared to standard intensity (all p<0.02) and age was predictive of reduced as compared to standard intensity (p<0.01); gait speed was not reliably predictive in either case. Conclusions: In this large cohort of older adults with hematologic malignancies, gait/treatment intensity mismatches occurred in over one-quarter of patients. Oncologists’ recommendations were predicted by age and PS but not gait speed. Given that gait speed is a strong predictor of survival in this population, oncologists should integrate it to minimize over- and under-treatment when making treatment recommendations. [Table: see text]
External validation of two predictive scores of chemotherapy toxicities among older patients with solid cancer, from ELCAPA prospective cohort.
Authors: Frelaut Maxime , Caillet Philippe , Culine Stephane , Paillaud Elena , Tournigand Christophe , Canoui-Poitrine Florence 
Published: May 2020

12050 Background: Severe chemotherapy toxicities are frequent among older patients, and may have a major impact on mortality, comorbidities, and quality of life. Two scores were developed to predict severe toxicities: Chemotherapy Risk Assessment Scale for High-age patients (CRASH) score, and Cancer and Aging Research Group Study (CARG) score. The main objective of the present study was to evaluate the predictive value of both scores on an external cohort. Secondary objective was to identify individual predictive factors of severe chemotherapy toxicities. Methods: The Elderly Cancer Patients (ELCAPA) survey consists in a prospective cohort including patients aged 70 years or older referred for a geriatric assessment (GA) before anticancer treatment, such as chemotherapy for solid cancer. CARG and CRASH score were retrospectively collected. Main endpoint was grade 3/4/5 toxicities for CARG-score, hematologic grade 4/5 and non-hematologic grade 3/4/5 toxicities for CRASH-score. Calibration and discrimination (Area Under ROC Curve, AUC) were evaluated. Results: From July 2010 to March 2017, 248 patients were included. Among them, 150 (61%) experienced severe toxicity as defined in CARG study, and 126 (51%) as defined in CRASH study. There was no increased risk of toxicity in intermediate and high risk groups of CARG-score compared to low risk group (OR = 0.3, IC95% [0.1 – 1.4], p= 0.1; and OR = 0.4, IC95%[0.1 – 1.7], p= 0.2 respectively, AUC-ROC = 0.55). Similarly, there was no more risk of severe toxicities in intermediate low, intermediate high, and high risk groups compared to low risk groups of CRASH combined score (respectively OR = 1, IC95% [0.3 – 3.6], p= 0.99; OR = 1, IC95% [0.3 – 3.4], p= 0.9; OR = 1.5, IC95% [0.3 – 8.1], p= 0.67; AUC-ROC = 0.52). A multivariate predictive model including cancer type, performance status (PS 0 vs. PS 1-2), number of severe comorbidities (Cumulative Illness Rating Scale for Geriatrics, CIRS-G, ≥1 grade 3 or 4 comorbidity), body mass index (BMI > 25 kg/m² protective vs. normal BMI), and Chemotox score (1 vs. 0) had an AUC of 0.78. Conclusions: Neither CARG nor CRASH score was predictive of severe chemotherapy toxicities in the ELCAPA cohort. There is a need to identify new predictors of chemotherapy toxicity in older patients with solid cancers.
Randomized clinical trial on the effect of a supervised exercise program on quality of life, fatigue, and fitness following esophageal cancer treatment (PERFECT study).
Authors: May Anne Maria , van Vulpen Jonna , Hiensch Anouk E , Ruurda Jelle P. , Nieuwenhuijzen Grard , Kouwenhoven Ewout , Groenendijk Richard PR , Van der Peet Donald , Hazebroek Eric J , Rosman Camiel , Wijnhoven Bas P.L. , van Berge Henegouwen Mark I. , Van Laarhoven Hanneke W.M. , van Hillegersberg Richard , Siersema Peter 
Published: May 2020

12055 Background: Patients with potentially curable esophageal cancer are often treated with chemoradiotherapy followed by surgery. This treatment might have a negative impact on physical fitness, fatigue and quality of life (QoL). In patients with other types of cancer, evidence suggests that physical exercise reduces treatment related side effects. We investigated whether a supervised exercise program also beneficially affects QoL, fatigue and cardiorespiratory fitness (CRF) in patients after treatment for esophageal cancer. Methods: The multicenter PERFECT study randomly assigned patients in the first year after esophagectomy to an exercise intervention (EX) or usual care (UC) group. EX patients participated in a 12-week moderate to high intensity aerobic and resistance exercise program supervised by a physiotherapist. UC patients were advised to maintain their physical activity levels. Attendance and compliance with the exercise intervention protocol were retrieved from exercise logs. QoL (primary outcome, EORTC-QLQ-30, range 0-100), fatigue (MFI-20, range 4-20) and CRF (cardiopulmonary exercise testing) were assessed at baseline and after 12 weeks (post-intervention). The outcomes were analyzed as between-group differences using either linear mixed effects models or ANCOVA adjusted for baseline and stratification factors (i.e. sex, time since surgery, center), according to the intention-to-treat principle. Results: A total of 120 patients (age 64±8) were included and randomized to EX (n = 61) or UC (n = 59). Patients in the EX group participated in 96% (IQR:92-100%) of the supervised exercise sessions and compliance with all parts of the exercise program was high ( > 90%). Post-intervention, global QoL was not statistically different between groups, but significant (p < 0.05) beneficial EX effects were found for QoL-Summary scores (between-group difference 3.5, 95% CI 0.2;6.8) and QoL-role functioning (9.4, 1.3;17.5). Physical fatigue wat non-significantly lower in the EX group (-1.2; -2.6;0.1, p = 0.08). CRF was significantly higher (VO2peak (1.8 mL/min/kg, 0.6;3.0) following the EX intervention. Conclusions: Patients were well capable to complete an intensive supervised exercise program after esophageal cancer treatment, which led to small but significant improvements in several aspects of QoL and cardiorespiratory fitness. Our results suggest that supervised exercise is a beneficial addition to routine care of patients with esophageal cancer. Clinical trial information: NTR5045 .