bluuebunny/crossref_metadata_2025_split huggingface dataset:
ESMO Magnitude of Clinical Benefit Scale (MCBS): An evaluation of systemic treatment trials for soft tissue sarcomas (STS).
Authors: Salawu Abdulazeez , Lemieux Christopher , Abdul Razak Albiruni Ryan 
Published: June 2021

11553 Background: Patients with STS have poor prognosis in the metastatic setting. Although some treatment options are associated with improved outcomes, such as progression-free (PFS) or overall survival (OS), the overall magnitude of clinical benefit can be unclear. The ESMO MCBS is a validated and reproducible tool developed to quantify the clinical benefit of treatments evaluated in trials ( www.esmo.org/guidelines/esmo-mcbs ). Herein, we report the application of ESMO MCBS to systemic treatment trials involving metastatic STS patients. Methods: A systematic search of Medline, Embase and Cochrane databases for adult phase II and III trials in advanced STS (01/1998 to 12/2020) was carried out. Gastrointestinal stromal tumor trials were excluded. Outcomes, including but not limited to OS, PFS, objective response rate (ORR), toxicity and quality of life (QoL) data were extracted and analyzed. Studies with outcomes that met the criteria for ESMO MCBS v1.1 were evaluated to generate a score of 1 to 5 (score of ≥ 4: substantial benefit). MCBS scoring of each study was performed by at least 2 co-authors for consensus. Results: Among 3454 abstracts screened, a total of 140 Phase II and 28 phase IIII trials were identified. A total of 41 studies fulfilled the criteria for ESMO MCBS scoring. These include 5 phase III studies, as well as 9 randomized and 27 single-arm phase II trials. Fifteen studies involved specific histology, while remaining 26 studies were of all STS subtypes. Chemotherapy, alone or in combination was evaluated in 29 trials, while molecular-targeted agents (MTA) and immune checkpoint inhibitors (IO) were evaluated in 11 and 3 studies, respectively (Table). The median MCBS score was 2 (range 1-4), regardless of drug class or combination. Only 3 studies, all randomized in design, had a MCBS score of 4. All three trials were in the 2nd line setting or beyond, where there is no standard control treatment. None of the trials, irrespective of drug class had a score of 5 and no study showed evidence of significant improvement in QoL. The observed MCBS scores were low, partly because the trials evaluated mainly comprise single-arm studies without QoL assessments, restricting to a maximum MCBS score of 3. Conclusions: Most systemic therapy trials in advanced STS did not confer substantial clinical benefit when evaluated using MCBS. Although randomized phase 3 trials remain the gold standard of treatment evaluation, clinical benefit evaluation of STS trials using tools such as MCBS may be useful. Incorporation of QoL evaluation, even in single-arm studies should be prioritized in metastatic STS trials.[Table: see text]
The efficacy and safety of anlotinib in refractory/recurrent/advanced pediatric solid tumors: A retrospective study.
Authors: Lu Suying , Hong Ye , Chen Huimou , Wu Liuhong , Zhu Jia , Wang Juan , Sun Feifei , Zhen Zijun , Que Yi , Zhang Lian , Sun Xiaofei , Huang Junting , Zhang Yizhuo 
Published: June 2021

11556 Background: Refractory and recurrent advanced pediatric solid tumors are short of effective treatment and with a dismal outcome, thus an urgent need for novel and effective treatment. The aim of the study is to evaluate the efficacy and safety of anlotinib, a novel and oral multi-target receptor tyrosine kinase inhibitor, in refractory or recurrent advanced pediatric solid tumors. Methods: The retrospective, single-institutional, observed study was conducted in Sun Yat-sen University cancer center in China. Refractory, recurrent, or advanced pediatric solid tumors patients treated with anlotinib between 2018 to 2020 were evaluated. Results: Forty-one patients and thirty patients were enrolled in the study to evaluated efficacy and safety, respectively. The objective response ratio (ORR) was 12.2% (95%CI 1.7-22.7): complete response (n = 0) and partial response (n = 5) (Table). The disease control rate (DCR) was 65.9% (95%CI 50.7-81). The median progression-free survival (PFS) was 2.87 months (95%CI 0.86-4.88). According to anlotinib treatment schedule, all patients were divided into three groups: anlotinib monotherapy (A, n = 16), anlotinib combined with immune checkpoint inhibitor treatment (A + ICI, n = 6), anlotinib combined with salvage chemotherapy (A + SC, n = 19). The ORR, DCR and median PFS for three groups were 6.3% (95%CI 7.1-19.6), 56.3% (95%CI 28.9-83.6), 2.43months, 16.7% (95%CI 26.2-59.5), 66.7% (95%CI 12.5-120.9), 1.13months, 15.8% (95%CI 2.3-33.8), 73.7% (95%CI 51.9-95.5), 2.87months, respectively. There was no significantly difference between three groups in aforementioned response index. The incidence rates of any grade and grade 3-4 adverse events were 80% and 20%, respectively. Bleeding (20%), hand-foot syndrome (13.3%), and diarrhea (13.3%) were the most common adverse events. Grade 3-4 adverse events include hypertension, hand-foot syndrome, diarrhea, anemia, and thrombocytopenia. There was no adverse events-related death. Conclusions: For heavily pretreated pediatric solid tumors, anlotinib may be an effective treatment with tolerable adverse events. Further prospective randomized controlled clinical study is warranted.[Table: see text]
Evaluation of homologous recombination deficiency (HRD) score and immuno-tumor microenvironment (iTME) as biomarkers of soft tissue sarcoma (STS) survival and response to immune checkpoint inhibitor therapy.
Authors: Zhang Chenlu , Guo Xi , Xu Fei , You Yang , Wang Zhiming , Zhuang Rongyuan , Liu Wenshuai , Ma Li-Jie , Tong Hanxing , Zhang Yong , Lu Weiqi , Liu Jun , Zhou Yuhong 
Published: June 2021

11568 Background: Soft tissue sarcoma (STS) are highly heterogenous in both histology and underlying genetic alterations, resulting in heterogenous outcomes of standard therapy. With recent stride of immunotherapies in oncology it is crucial to find the optimal match of the new therapies to disease subtypes. HRDScore and iTME parameters are two top candidate biomarkers to predict clinical outcomes in complex diseases such as STS. Methods: We prospectively profiled 102 Chinese STS patients who had received more than 1 line of prior treatment, mainly chemo-drugs. We then classified the patients according to their HRDScore (calculated from WES data using the Richardson method, ref. Telli M.L. et al. Clin. Cancer Res. 2016) and iTME parameters (calculated from RNAseq data using CIBERSORT method). Lastly, we tested the correlation of HRDScore or iTME with patient survival and clinic outcomes of anti-PD-1/L1 based combination therapy. Results: The histological subtypes of the patients included 32 LMS, 44 LPS, and 26 others (such as UPS, clear cell, myxofibrosarcoma, uterus LMS etc.). The top mutation genes (frequency > 5%) included TP53 29%, KMT2C 16%, NOTCH2 9%, ATRX 8%, NF1 8%, RB1 8% and PTEN 6%. The patients could be classified to HRD-high or HRD-low (HRDScore > or < = 42). Alternatively, unsupervised clustering of iTME revealed three patient subgroups (named iTME-I, -II, and -III). While all the three groups are characterized by a generally suppressed immune environment, iTME-I have high proportion of M0 macrophages and median M2 macrophages; iTME-II have high proportion of M2 macrophages but low M0 cells; and iTME-type III are low in both M0 and M2 cells. No significant M1 cells present in all the three iTME groups. Patient survivals were correlated with the iTME types but not HRDScore in Kaplan-Meyer analysis. The trend of survival time was iTME-III > iTME-II > iTME-I, with an HR = 0.156 for iTME-III over iTME-I (p = 0.008, log-rank test). Treatment response of anti-PD-1/L1 based combination therapies also showed a positive correlation to iTME-III, but not HRDScore although the small sample size prevented a definitive conclusion. Clinical evaluation of the 22 patients who received anti-PD-1/L1 therapy showed 1 PD (20%) and 4 SD/PR (80%) in iTME-III, 4 PD (40%) and 6 SD/PR (60%) in iTME-II, and 1 PD (33%) and 2 SD (67%) in iTME-I. Conclusions: iTME is a better biomarker than HRDScore in STS for survival and treatment outcomes. Differential Infiltration of M0 and M2 macrophages can distinguish patients with different survival and response to anti-PD-1/L1 combination therapy. The iTME subtypes may be used for treatment screen of combination immunotherapy but larger and randomized clinical studies are required to validate the discovery.
Intensity of end-of-life care for gynecologic cancer patients by primary oncologist specialty.
Authors: Hicks-Courant Katherine , Kanter Genevieve P. , Schapira Marilyn M. , Brensinger Colleen , Liu Qing , Ko Emily Meichun 
Published: June 2021

12032 Background: The impact of primary oncologist specialty, medical oncology (MO) versus gynecologic oncology (GO), on intensity of care at the end of life (EOL) in elderly patients with gynecologic cancer is unclear. Methods: This retrospective cohort study used Surveillance, Epidemiology and End Results (SEER) Medicare data. Subjects were fee-for-service Medicare enrollees over 65 years old, who had seen a GO or MO in an outpatient setting in the last year of life and died of a gynecologic cancer between 2006 and 2015. The primary oncologist was defined as the provider with the majority of outpatient visits in the last year of life. The primary outcome was intensity of care at the EOL, a composite score defined by receipt of chemotherapy in the last 14 days of life, death in the hospital, enrollment in hospice for less than three days, more than one ED visit, more than one hospital admission, spending more than 14 days in the hospital, or any ICU admission in the last 30 days of life. Simple and multivariable linear regression analyses were conducted to evaluate for differences in EOL care outcomes by primary oncologist specialty. Linear regressions were repeated after creating a more similar control group through nearest-neighbor propensity score matching, with and without replacement. Results: Of 12,189 subjects, 63% were primarily treated by a MO and only 27% by a GO for EOL care. Most died of ovarian cancer (55.1%), followed by uterine (31.4%), cervical (6.9%), and other cancers (6.7%). Compared to GO patients, MO patients were younger, more likely to be white, married, not dual-eligible, higher stage, and to die of ovarian cancer. Overall, 55.4% (95% CI 54.73-56.49) received intense care at the EOL. Although both specialties engaged in high levels of intense EOL care, the adjusted rates for GO (54.03%; 95% CI 52.28-55.77) were significantly less compared to MO (56.53%; 95% CI 55.36-57.69; p=0.023) in unadjusted and adjusted analyses of the entire and propensity-matched cohorts (Table). Conclusions: Approximately 2/3 of women with gynecologic cancer will receive EOL care from a MO, compared to 1/3 from a GO. Both specialists engage in high levels of intense EOL care in over half of their patients, although GO less so. Future work should focus on identifying approaches to reduce high-intensity EOL care, which may include additional training or incorporation of palliative medicine into cancer care.[Table: see text]
Code status and outcomes in patients with cancer and COVID-19: A COVID-19 and cancer consortium (CCC19) registry analysis.
Authors: Loggers Elizabeth Trice , Wulff-Burchfield Elizabeth Marie , Subbiah Ishwaria Mohan , Khaki Ali Raza , Egan Pamela , Farmakiotis Dimitrios , Phull Hardeep , Nakasone Elizabeth , Labaki Chris , Yu Peter Paul , Joshi Monika , Griffiths Elizabeth A. , Wise-Draper Trisha Michel , Jani Chinmay , Thakkar Astha , Puc Matthew , Hwang Clara , Mavromatis Blanche H. , Shah Dimpy P , Warner Jeremy Lyle 
Published: June 2021

12035 Background: In-hospital mortality among patients with cancer (pts) and COVID-19 infection is high. The frequency of, and factors associated with, do-not-resuscitate (DNR) or do-not-intubate (DNI) orders at hospital admission (HA), and their correlation with care, has not been well studied. In November 2020, we began collecting this information for pts who were hospitalized at initial presentation in the CCC19 registry (NCT04354701). Methods: We investigated: 1. the frequency of, and factors associated with, DNR/DNI orders at HA; 2. change in code status during HA; and 3. the correlation between DNR/DNI orders and palliative care consultation (PC), mortality or length of stay (LOS). We included hospitalized, adult pts with cancer and COVID-19 from 57 participating sites. Reported characteristics include age, ECOG performance status (PS), and cancer status. Comparative statistics include 2-sided Wilcoxon rank sum and Fisher’s exact tests. Results: 744 pts had known baseline and/or changed code status (CS); most (79%) maintained their baseline CS (Table). Those with DNR±DNI orders at HA were older (median age 79 vs 69 yrs, p<0.001) and more likely to have: ECOG PS 2+ vs 0-1 (45% vs 22%, OR 3.95, p<0.001), metastatic disease (45% vs 35%, OR 1.72, p=0.005) and progressing cancer (32% vs 16%, OR 2.69, p<0.001), but equally likely to have received systemic anticancer therapy in the prior 3 months (38% vs 45%, p=0.15). N=192 pts with a change in CS from full to DNR±DNI were younger (median age 73), had better PS (37% ECOG PS 2+), and were less likely to have progressing cancer (23%) than those with DNR±DNI orders at baseline. However, their LOS was significantly longer, median 9 vs 6 days, p<0.001. Compared to those with DNR±DNI orders at HA, pts whose CS changed to DNR±DNI were more likely to die, OR 2.94, 95% CI 1.76-4.97, p<0.001. PC was obtained in 106 (14%) pts and associated with transition to DNR±DNI in 47 (44%), affirmation of admission CS in 58 (55%), and reversal in 1 (1%). Median LOS for pts receiving PC was 11 vs 6 days, p<0.001. Conclusions: In our sample, the majority of patients with cancer and COVID-19 were full code at hospital admission. DNR±DNI status, whether at baseline or assigned during the hospital course, was associated with worse prognosis. Longer length of stay for patients changing code status and/or receiving palliative care consultation was observed likely suggesting earlier palliative care consultation is an important, but likely underutilized component in the care of patients with cancer and COVID-19.[Table: see text]
High intensity interval training safety and efficacy in patients with advanced NSCLC receiving systemic treatment: Results of a prospective trial.
Authors: Nait Ajjou Myriam , Bastarache Guillaume , Walsh Emily , Routy Bertrand , Blais Normand , Tehfe Mustapha , Coulombe Genevieve , Alameddine Raafat , Florescu Marie 
Published: June 2021

12054 Background: Patients with advanced NSCLC experience fatigue and physical deconditioning altering their quality of life. Safety and feasibility of high intensity exercise in advanced NSCLC has not been explored yet. Methods: We report the results of a single-center, prospective two-arm study. Patients with advanced NSCLC actively receiving systemic therapy or having completed treatment less than 2 months prior to enrollment were included. Patients were allocated to either an intervention arm consisting of kinesiologist supervised high intensity interval training (HIIT) at 2 sessions per week for a total of 12 weeks; or a control arm of home exercise guided by an informative pamphlet. All patients were evaluated at baseline, 6 and 12 weeks by a kinesiologist. Quality of life (QoL) exercise surveys and measurement of strength were measured. Results: Sixty patients were enrolled between January 2018 and March 2020. The study was interrupted due to COVID-19. Thirty-two patients were included in the exercise program and 28 patients in the control group. Both groups were balanced in respect to baseline characteristics. A total of 32 (53%) patients went off protocol, 13 (18%) patients stopped due to symptomatic disease progression which included 2 (3%) deaths, 2 (3%) stopped due to COVID-19 preoccupations and the remaining patients withdrew for other reasons. 42 (70%) patients were evaluated at 6-weeks and 28 (47%) completed the 12-week follow-up, with equal distribution in each group. There were no significant difference at 12 weeks in the physical assessment nor the overall QoL scores between both groups: FACT-L on 135 points (+4.1 vs +1.7, p = 0.342) and FACIT on 52 points (+3 vs -0.2, p = 0.832). Patients in the exercise group demonstrated a significant improvement at 12 weeks in the Lung Cancer Symptoms domain on 28 points (22.3 vs 19.8, p = 0.015) as well as the Physical Wellbeing domain on 28 points (23.6 vs 20.6, p = 0.056) compared to the control group, respectively. No significant exercise related complications were reported. After the study, 9 of the 14 patients (64%) who completed the HIIT program continued to exercise virtually with a kinesiologist in contrast to none in the control group. Conclusions: This study demonstrated the safety and potential benefit of a HIIT program on lung-specific and physical wellbeing in patients with advanced NSCLC on active treatment. This study provides further support on the role of supervised physical exercise in patients living with cancer. Clinical trial information: 16.229.
Weight management following endometrial cancer treatment: A pilot trial to evaluate the efficacy of the profile by Sanford program.
Authors: Bell Maria , Reed Valerie , Wernisch Jan , Papini Natalie , Herrmann Steve 
Published: June 2021

12056 Background: Excess weight and weight gain are risk factors for endometrial cancer and cancer recurrence following treatment for women with endometrial cancer. Conversely, weight loss among women with obesity has been shown to reduce endometrial cancer risk. Intensive behavioral weight management programs may be an effective method to improve health and reduce weight following treatment. Methods: Twenty-two women following endometrial cancer treatment (age = 59.4 ± 11.5; weight = 241.3 ± 46.3; BMI = 40.5 ± 7.8; time since last treatment 19 ± 17.4 months) were enrolled in a behavioral weight management program and followed for 12 months and 28 matched controls (age = 58.4 ± 11.5; weight = 246.9 ± 60.3; BMI = 41.6 ± 8.6) were assessed over 12 months. The program consists of weekly health coaching meetings to discuss nutrition, activity, and behavior change topics. The nutrition plan targets ≥4 cups of vegetables per day, a ‘lean and green’ grocery meal, complimented with meal replacement foods to provide a nutritionally complete meal plan. Cost of participant membership, coaching, and meal replacements were covered for 6 months and available to purchase for months 7-12. Results: The treatment group completed 28.3 ± 14.1 appointments throughout 12 months resulting in an average weight change of -31.2 ± 17.3 pounds (-13.3 ± 7.4%) at 6 months and -36.1 ± 27.6 pounds (-15.3 ± 11.4%) at 12 months (all p<0.001). Controls had a weight change of -3.9 ± 18.4 pounds (-2.3 ± 7.6%) at 12 months which was significantly different than the treatment group (p<0.001). BMI was significantly reduced in the treatment group at 6 months (-4.8 ± 4.5, p<0.001) and 12 months (-5.2 ± 5.9, p<0.001) and significantly different than in the control group at 12 months (-0.9 ± 3.2, p=0.007). Conclusions: This behavioral weight management program with health coaching and structured nutrition provided clinically significant weight loss that was sustained to 12 months. Future research should examine long-term enrollment in the Profile by Sanford program with reduction in endometrial cancer recurrence.[Table: see text]
Late cardiac events and their impact on overall survival in patients receiving an allogeneic stem cell transplant.
Authors: Auberle Christine , Lenihan Daniel John , Gao Feng , Cashen Amanda F. 
Published: June 2021

12070 Background: There is limited data on the impact of cardiac disease on long term outcomes of allogeneic stem cell transplant (alloSCT). We sought to describe the importance of adverse cardiac events on long term outcomes of alloSCT. Methods: We performed a retrospective analysis of pts who underwent alloSCT from 2007 to 2017 and survived at least one year after transplantation. Late cardiac events were defined as occurring at least one year after transplant. Data was obtained through electronic medical records and the transplant database at Siteman Cancer Center. Univariate Cox proportional hazards model was used to assess the effect of baseline characteristics on cardiac events and overall survival. Time-dependent Cox model was used to determine the effect of cardiac events on overall survival. Gray’s sub-distribution methods, while accounting for death as a competing risk, were used to calculate the incidence of cardiac events. Results: 804 pts met our criteria (58.7% male, average age 49.7 years). Median duration of follow up was 59.3 months. Most pts were transplanted for acute myeloid leukemia (49.9%) and had a match-related or unrelated donor (56.1%). The majority received myeloablative conditioning (74.4%), and 34.6% received total body irradiation (TBI). The most common late cardiac events were an elevated troponin (20.9%), elevated brain natriuretic peptide (BNP) or N-terminal pro-BNP (16.9%), shock (15.3%), and reduced left ventricular ejection fraction (LVEF) defined as < 45% (10.4%). Pts were at significantly increased hazard of developing late cardiac events if they were of male sex (HR 1.29, P = 0.026), had pre-existing diabetes (HR 1.45, P = 0.022), pre-existing atrial fibrillation or flutter (HR 1.77, P = 0.008), history of congestive heart failure (HR 1.82, P = 0.032) or increasing age at time of transplant (HR 1.02, P < 0.001). Primary disease for alloSCT, donor type, TBI and myeloablative conditioning regimen had no significant association with late cardiac events. The cumulative incidence of developing any cardiac event in the period 1-5 years after transplant was 28.2% with a cumulative incidence of shock at 13.6%, reduced ejection fraction at 8.7% and an atrial arrythmia at 7.1%. Most cardiac events were associated with an increased risk of death (Table). Conclusions: Cardiac events after alloSCT have a substantial impact on overall survival. Efforts to optimally manage cardiac disease after alloSCT are likely to have a major benefit, and cardiac protection should be a major focus for post-alloSCT follow up.[Table: see text]