bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic role of % changes in longest tumor diameter (LTD) in localized high-risk soft tissue sarcoma (STS) treated with neoadjuvant chemotherapy in a randomized clinical trial.
Authors: Stacchiotti Silvia , Morosi Carlo , Braglia Luca , Palmerini Emanuela , Quagliuolo Vittorio , Martin Broto Javier , Lopez-Pousa Antonio , Grignani Giovanni , Brunello Antonella , Blay Jean-Yves , Tendero Oscar , Diaz Beveridge Robert , Lugowska Iwona , Fontana Valeria , Marchesi Emanuela , Palassini Elena , Bruzzi Paolo , Merlo Franco Domenico , Casali Paolo Giovanni , Gronchi Alessandro 
Published: May 2020

11558 Background: We investigated the prognostic relevance of % change in LTD in patients (pts) with localized high-risk STS treated with neoadjuvant chemotherapy in a phase 3 randomized trial (NCT01710176), aimed at comparing 3 cycles of a neoadjuvant histology-tailored (HT) over 3 cycles of standard anthracycline + ifosfamide chemotherapy (S). Methods: Pts with localized high-risk STS of extremities or trunk wall, and a diagnosis of myxoid liposarcoma, leiomyosarcoma, synovial sarcoma, malignant peripheral nerve sheath tumors, undifferentiated pleomorphic sarcoma were randomly assigned to receive 3 cycles of S or HT. Pts affected by myxofibrosarcoma, pleomorphic liposarcoma, pleomorphic rhabomyosarcoma unclassified spindle cell sarcoma were prospectively registered and treated by S. Change of LTD was assessed comparing baseline dimension with that measured after 3 cycles of S or HT, before surgery. Only pts treated with neodjuvant chemotherapy alone were selected for the analysis. We first investigated Overall Survival (OS) from surgery of the groups identified by “any % reduction”, “no-change” or “increase” in LTD by Kaplan-Meier estimates and log-rank tests. Then we searched for cutoffs able to separate prognosis among pts with a LTD reduction applying the change-point method proposed by Contal - O’Quigley. Results: Of 325 pts who entered the study and evaluable for response, 181 received neoadjuvant chemotherapy alone (92 S and 89 HT group respectively) and were analyzed, while 144 received concurrent chemo-radiotherapy and were excluded. In the whole population, % changes in LTD were significantly associated (log rank p = 0.032) to OS. “Any % reduction in LTD (101/181pts) displayed a better prognosis compared to “no-change” (28/181 pts) or “any % increase” (52/181). The change-point analysis was applied to all, S and HT groups separately; a cutoff of = / > 18.75% decrease in LTD was the optimal predictor of outcome for the S group (p = 0.031), while no size cut-off could be identified for the HT group. Conclusions: In our study, % change in LTD of pts treated with neoadjuvant chemotherapy for localized high-risk STS correlated with OS. However, a % decrease in LTD cut-off able to predict the best outcome could be identified only for pts treated in the S group, while no differences in outcome were found by any % LTD change in the HT group. Interestingly, the LTD cut-off identified in the S group was lower than the one selected to define a response by RECIST ( = / > 18.75% decrease in LTD vs = / > 30%). Clinical trial information: NCT01710176 .
Nationwide incidence of sarcomas and tumors of intermediate malignancy in the NETSARC network with central pathology review: Correlation with published clinical research.
Authors: De Pinieux Gonzague , Karanian Marie , Le Loarer Francois , Le Guellec Sophie , Terrier Philippe , Bouvier Corinne , Battistella Maxime , Robin Yves Marie , Emile Jean-François , Moreau Anne , Larousserie Frederique , Leroux Agnès , Stock Nathalie , Laé Marick , Collin Françoise , Italiano Antoine , Le Cesne Axel , Penel Nicolas , Coindre Jean Michel , Blay Jean-Yves ,   on behalf of the RREPS/RESOS/NETSATC ( NETSARC+) and French Sarcoma Group-Groupe d’Etude des Tumeurs Osseuses (GSF-GETO) Networks
Published: May 2020

11560 Background: Since 2010, presentation to a designated sarcoma tumor board and pathological review by an expert network are mandatory for sarcoma patients in France. NETSARC+ (merging the 3 initial RREPS, RESOS & NETSARC) collected prospectively all cases of reviewed sarcomas and tumors of intermediate malignancy (TIM) nationwide. We report on the incidence of subtypes according to WHO classification from 2013 to 2016. Methods: Sarcoma expert pathologists reviewed samples were all prospectively integrated in the database; the results using the latest WHO classification are presented for the years 2013 to 2016, including yearly variations. Correlation of the incidence of each histotype with dedicated published clinical trials was conducted. Results: 139 different histological subtypes are reported among the 25172 patients with sarcomas (n = 18710, 64%) or TIM (n = 6460, 36%), respectively n = 5838, n = 6153, n = 6654, and n = 6527 yearly from 2013 to 2016. Over these 4 years, the observed yearly incidence of sarcomas, TIM, and all was therefore 79.7, 24.9 and 95.1/10e6/year, above that previously reported. GIST, liposarcoma, leiomyosarcomas, undifferentiated sarcomas represented 13%, 13%, 11% and 11% of all sarcomas. Only GIST, as a single entity exceeded a yearly incidence above 10/million per year. There were respectively 30, 63 and 66 different histological subtypes of sarcomas or TIM (single entities or lumped together, e.g. MPNST, or vascular sarcomas...) with an incidence ranging from 10 to 1/10e6/year, 1-0.1/10e6 per year, or < 0.1/10e6/year respectively. The 2 later “incidence groups” included 21% of the patients. The incidence of 8 histotypes varied significantly over this 4 years. Patients with tumors with an incidence above 1/10e6 per year have significantly higher numbers of dedicated published phase III and phase II clinical trials (p < 10e-6). Conclusions: This nationwide registry of sarcoma patients with an histology reviewed by sarcoma experts shows that the incidence of sarcoma and TIM is higher than previously reported, may vary over years for some histotypes, and that tumors with an incidence < 10e6 have a much lower access to clinical trials.
A randomized phase II study of MLN0128 (M) versus pazopanib (P) in patients (pt) with advanced sarcoma (Alliance A091304).
Authors: Ingham Matthew , Mahoney Michelle R. , Remotti Fabrizio , Shergill Ardaman , Dickson Mark Andrew , Riedel Richard F. , Attia Steven , Elias Anthony D. , Liebner David A. , Agulnik Mark , Thornton Katherine Anne , Monga Varun , Van Tine Brian Andrew , Schwartz Gary K. , Tap William D. 
Published: May 2020

11562 Background: Soft tissue sarcoma (STS) is a heterogeneous malignancy of connective tissue. Although mTOR is implicated in STS pathogenesis, clinical activity from mTORC1 inhibitors is modest. M, a potent selective mTORC1/mTORC2 inhibitor, was more effective in STS preclinical models than inhibitors of mTORC1, IGF1R and mTORC1+IGF1R, owing to more complete suppression of PI3K/AKT/mTOR and abrogation of feedback AKT activation. P, an oral multikinase inhibitor, is approved for non-adipocytic STS and often used after progression (PD) on chemotherapy. In phase 1, the RP2D of M was 30 mg weekly. A091304 was to evaluate M as a novel targeted therapy for STS. Methods: In A091304, pts were randomized 1:1 to M 30 mg weekly or P 800 mg daily. Eligibility required Eastern Cooperative Oncology Group PS ≤ 1, progression on ≥ 1 prior chemotherapy and specific STS subtypes (cohort 1: UPS; 2: LMS; 3: MPNST, SS). Crossover to M was allowed after PD on P. 1° endpoint was progression-free survival (PFS). Assuming median PFS of P was 4.6 months (mo), 98 pts yielded 80% power to detect a hazard ratio of 0.66 favoring M [1-sided test, alpha = 0.15] and including 1 planned futility analysis. 2° endpoints were response rate, clinical benefit rate (CBR) at 4 mo and safety. After 4 of the first 12 pts randomized to P experienced ≥ grade (gr) 3 toxicity, the study was amended to begin at P 400 mg, allowing titration to 800 per investigator discretion. Results: After protocol amendment, 114 pt underwent randomization (M: 56, P: 58), and 111 initiated treatment. Median PFS was 2 mo for M and 2.1 mo for P (HR = 1.47; 1-sided 85% upper confidence boundary = 1.85), with 2 partial responses in each arm. CBR was 5.4% for M and 13.8% for P. Median OS was 10.7 mo for M and 13.9 mo for P (HR = 1.41; 95% CI 0.80-2.49). 26/43 pt with PD on P crossed over to M. Median PFS after crossover was 1.8 mo (95% CI 1.5-3.5). Gr 3 drug-related adverse events (AEs) occurred in 36% on M and 41% on P; gr 4 toxicity was rare. AEs were consistent with known effects of M and P. Conclusions: P at 400 mg daily (allowing escalation to 800 mg per investigator discretion) demonstrated a shorter PFS as compared prior randomized studies with P. Despite this, M failed to demonstrate superior clinical activity as compared to P at the interim analysis. Further work will examine activity within histology-specific cohorts and evaluate available tissue samples for evidence of pharmacodynamic activity. Support: U10CA180821, U10CA180882, U10CA180888, UG1CA233324 (SWOG); https://acknowledgments.alliancefound.org . Clinical trial information: NCT02601209 .
Effects of electroacupuncture and auricular acupuncture for chronic pain in cancer survivors: The PEACE randomized controlled trial.
Authors: Mao Jun J. , Liou Kevin , Panageas Katherine , Baser Raymond E , Romero Sally A. D. , Li Qing Susan , Xiao Han , Bao Ting , Kantoff Philip W. 
Published: May 2020

12004 Background: The national opioid crisis has created new challenges in oncology pain management and highlighted an urgent need for non-pharmacological treatments. We evaluated the comparative effectiveness of electro-acupuncture (EA) and auricular acupuncture (AA) versus usual care (UC) for chronic musculoskeletal pain in cancer survivors. Methods: We conducted a randomized controlled trial of cancer survivors experiencing moderate-severe musculoskeletal pain for at least 3 months. EA used a semi-individualized protocol involving electrical stimulation of needles placed in the body. AA used the standardized Battlefield Acupuncture protocol involving up to 10 needles placed in the ears. EA and AA groups received 10 weekly treatments, whereas participants in the UC group received standard care prescribed by their providers. The primary endpoint was average pain severity change measured by the Brief Pain Inventory at week 12 compared to baseline. Functional interference and quality of life were secondary outcomes. We analyzed longitudinal mixed-effects models based on intent-to-treat principles. Results: Among 360 participants, mean age (SD) was 62.1 (12.7) years, 251 (69.7%) were women, and 88 (24.4%) were non-white. Compared from baseline to week 12, EA significantly reduced pain severity by 1.9 points (95% Confidence Interval 1.5-2.3, p < 0.001), and AA significantly reduced pain severity by 1.6 points (1.1-2.0, p < 0.001). AA was non-inferior to EA at reducing pain severity (p = 0.04). Both EA and AA also significantly improved functional interference (both p < 0.001), physical health (both p < 0.001), and mental health (p = 0.003, p < 0.001) compared to UC. Adverse events (AEs) were mild in both groups; however, 16 (11.2%) in AA stopped treatment due to AEs (mostly ear discomfort) as compared to 1 in EA (0.7%), p = 0.001. Conclusions: Among cancer survivors with chronic musculoskeletal pain, both EA and AA effectively reduced pain and improved quality of life. AA was non-inferior to EA at reducing pain but associated with higher discontinuation rates. These results will guide implementation of acupuncture in oncology care to address the unmet pain management needs of cancer survivors in the era of the opioid epidemic. Clinical trial information: NCT02979574 .
Neuroleptic rotation for refractory agitation in cancer patients with delirium in the acute palliative care unit: A double-blind randomized clinical trial.
Authors: Hui David , De La Rosa Allison , Wilson Annie , Nguyen Thuc , Wu Jimin , Delgado Guay Marvin , Azhar Ahsan , Arthur Joseph Anthony , Epner Daniel E. , Haider Ali , De La Cruz Maxine Grace Jaucian , Heung Yvonne , Tanco Kimberson Cochien , Dalal Shalini , Armstrong Terri , Breitbart William , Bruera Eduardo 
Published: May 2020

12006 Background: Terminal agitation commonly occurs in the last days of life and is highly distressing. The role of neuroleptics is controversial and few studies have examined agitation as a primary outcome. We assessed the effect of 3 neuroleptic strategies on refractory agitation in cancer patients with terminal delirium. Methods: In this single-center, double-blind, double-dummy parallel group randomized trial, patients admitted to a palliative and supportive care unit with refractory agitation despite low dose haloperidol were randomized in a 1:1:1 ratio to (1) haloperidol dose escalation, (2) neuroleptic rotation to chlorpromazine, or (3) combined haloperidol and chlorpromazine. Intravenous medications at equivalent doses were scheduled every 4 h and every 1 h as needed until discharge. The primary outcome was change in Richmond Agitation Sedation Scale (RASS) from time 0 to 24 hours. With 15 patients per group and 13 measurements over time, we had 90% power to detect an effect size of 0.2 with alpha=2.5%. One way ANOVA was used to examine within group differences. We also compared among groups with the Wilcoxon rank sum test. Results: 68 patients were enrolled and 45 received the blinded study interventions. The median survival was 73 h (95% CI 49, 106 h). RASS decreased significantly within 30 minutes and remained low at 24 hours in the dose escalation group (mean RASS change between 0 and 24 h [95% CI]: -3.6 [-5, -2.2]) v. rotation group (-3.3 [-4.4, -2.2]) v. combination group (-3 [-4.6, -1.4]), with no difference among groups (P=0.71). A majority of patients were perceived to be more comfortable after treatment by blinded caregivers (escalation v. rotation v. combination: 62% v. 71% v. 60%; P=0.83) and bedside nurses (64% v. 75% v. 64%; P=0.82); however, the rotation group had significantly fewer breakthrough restlessness (escalation v. rotation v. combination: 73% v. 19% v. 50%; P=0.009), required fewer upward dose titration (escalation v. rotation v. combination: 27% v. 6% v. 50%; P=0.03) and required less rescue neuroleptics in the first 24 hours (haloperidol equivalent: 4 mg vs. 2 mg vs. 6 mg, P=0.09, trend only). Hypotension was more frequently observed with chlorpromazine. Overall survival did not differ (>0.99). Conclusions: Preliminary data from this study supported that all 3 strategies of neuroleptics reduced agitation and improved comfort in patients with terminal delirium; however, neuroleptic rotation provided better agitation control and confirmatory studies are needed. Clinical trial information: NCT03021486 .
A phase III randomized, double-blind placebo controlled study of armodafinil (Nuvigil) to reduce cancer-related fatigue in patients with high-grade glioma (Alliance A221101).
Authors: Porter Alyx B. , Liu Heshan , Kohli Sadhna , Cerhan Jane H. , Sloan Jeff A. , McMurray Ryan , Le-Rademacher Jennifer , Loprinzi Charles L. , Villano John L. , Kizilbash Sani Haider , Mehta Minesh P. , Jaeckle Kurt A. , Brown Paul D. 
Published: May 2020

12007 Background: Up to 96% of patients with high grade glioma (HGG) report moderate to severe fatigue. Armodafinil, the R-enantiomer of modafinil, is a psychostimulant with low potential for abuse that has shown potential for improving severe fatigue in HGG patients. Methods: In this phase III double blinded placebo-controlled study, adults with HGG and moderate to severe fatigue, > 4 weeks after completing radiotherapy, were randomized to receive armodafinil daily (150 mg or 250 mg) or placebo for a total of 8 weeks. The primary outcome was efficacy in treating severe fatigue. Secondary outcomes included evaluation of tolerability, neurocognitive function, and quality of life. Patients were evaluated at baseline, 4 and 8 weeks. Results: A total of 328 patients were enrolled between 6/3/13-3/1/19. There were 103 (150 mg arm), 97 (250 mg arm) and 97 (placebo arm) evaluable patients with primary endpoint data available. The median age was 60 years (20-85) with a median Brief Fatigue Inventory (BFI) worst fatigue score of 8 (6-10). 60.3% were male, 80.5% received concomitant chemotherapy, and 39.7% were on corticosteroids. The global fatigue score at end of weeks 4 and 8 were lower than at baseline (p<0.0001) and in the 250 mg arm than placebo (p=0.0356) and was higher for corticosteroid users than non-users (p=0.0002). There was no statistically significant difference for clinically meaningful improvement in BFI usual fatigue score from baseline to end of week 8 between the three arms (p=0.9601). Patients reported an improvement in concentration at week 4 from baseline on the 150 mg arm(P=0.0311). There was no statistically significant difference on neurocognitive tests from baseline to end of week 4 (p>0.05) or week 8 (p>0.05) between arms. More patients reported insomnia on the 250 mg arm (p=0.0083). Conclusions: There is no meaningful benefit of the use of armodafinil to reduce moderate to severe fatigue in patients with HGG. In certain cases there may be benefit of armodafinil 150 mg to aid concentration without the risk of insomnia.Support: UG1CA189823;U10CA180868 (NRG). Clinical trial information: NCT01781468 .
Geriatric assessment-driven intervention (GAIN) on chemotherapy toxicity in older adults with cancer: A randomized controlled trial.
Authors: Li Daneng , Sun Can-Lan , Kim Heeyoung , Chung Vincent , Koczywas Marianna , Fakih Marwan , Chao Joseph , Chien Leana , Charles Kemeberly , Fernandes Dos Santos Hughes Simone , Trent Monica , Roberts Elsa , Soto Perez De Celis Enrique , Jayani Reena , Katheria Vani , Moreno Jeanine , Kelly Cynthia , Sedrak Mina S. , Hurria Arti , Dale William 
Published: May 2020

12010 Background: Geriatric assessment (GA) can predict chemotherapy (chemo) toxicity in older adults (age ≥65) with cancer. However, evidence regarding the effect of GA-driven intervention (GAIN) on the incidence of chemo toxicity has been limited. Therefore, we conducted a randomized controlled trial evaluating the impact of GAIN vs. standard of care (SOC) on chemo toxicity in older adults with cancer. Methods: Patients (pts) age ≥65, diagnosed with a solid malignancy, and starting a new chemo regimen at City of Hope were eligible (NCT02517034). In a 2:1 ratio, 600 pts were randomly assigned to either GAIN (n = 398) or SOC (n = 202) arms. All pts completed a baseline GA prior to chemo. In the GAIN arm, a multidisciplinary team led by a geriatric oncologist, nurse practitioner, social worker, physical/occupation therapist, nutritionist, and pharmacist, reviewed GA results and implemented interventions based on predefined triggers built into the GA’s various domains. In the SOC arm, GA results were sent to treating oncologists to use at their discretion. Pts were followed until either end of chemo or 6 months after start of chemo, whichever occurred first. The primary endpoint was incidence of grade 3-5 chemo-related toxicity (NCI CTCAE v.4.0). Secondary endpoints included advance directive (AD) completion, emergency room (ER) visits, hospitalizations, and average length of stay (ALOS). Chi-square and Fisher’s exact tests were used to compare the categorical outcomes, and Kruskal-Wallis test was used to compare the ALOS between arms. Results: Pt characteristics were balanced between arms. Median age was 71 (range 65-91). Cancer types included: 33% gastrointestinal, 23% breast, 16% lung, 15% genitourinary, and 13% other. Most (71%) had stage IV disease. The incidence of grade 3-5 chemo-related toxicity was 50.5% (95% CI: 45.6-55.4%) in the GAIN arm and 60.4% (95% CI: 53.7-67.1%) in the SOC arm (p = 0.02). Compared to SOC, the GAIN arm had a reduction of 9.9% (95% CI: 1.6-18.2%) in chemo-related toxicity. At the end of study, AD completion increased 24.1% in the GAIN arm vs. 10.4% in the SOC arm (p < 0.001). No significant differences in ER visits (27.4% vs. 30.7%), hospitalizations (22.1% vs. 19.3%), or ALOS (median 4.8 vs. 5.0 days) were observed between the GAIN and SOC arms, respectively. Conclusions: Integration of multidisciplinary GA-driven interventions reduced grade 3-5 chemo-related toxicity and improved AD completion in older adults with cancer. GA-driven interventions should be included as a part of cancer care for all older adults. Clinical trial information: NCT02517034 .
Randomized trial of a symptom monitoring intervention for hospitalized patients with advanced cancer (NCT03396510).
Authors: Nipp Ryan David , Horick Nora K. , Qian Carolyn L. , Kaslow-Zieve Emilia R. , Azoba Chinenye C. , Elyze Madeleine , Knight Helen Perry , Jackson Vicki A. , Ryan David P. , Greer Joseph A. , El-Jawahri Areej , Temel Jennifer S. 
Published: May 2020

12014 Background: Hospitalized patients with advanced cancer experience a high symptom burden, which is associated with poor clinical outcomes and increased health care use. Symptom monitoring interventions are increasingly becoming standard of care in oncology, but studies of these interventions in the hospital setting are lacking. We evaluated the impact of a symptom monitoring intervention in hospitalized patients with advanced cancer. Methods: We randomly assigned hospitalized patients with advanced cancer who were admitted to the oncology service to a symptom monitoring intervention or usual care. Patients in both arms reported their symptoms (Edmonton Symptom Assessment System [ESAS] and Patient Health Questionnaire 4 [PHQ4], higher scores on both indicate greater symptom severity) daily via tablet computers. Patients assigned to the intervention had their symptom reports presented graphically with alerts for moderate/severe symptoms during daily oncology rounds. The primary endpoint was the proportion of days with improved symptoms for those who completed two or more days of symptoms. Secondary endpoints included hospital length of stay (LOS) and readmission rates. Results: From 2/2018-10/2019, we randomized 390 patients (76.2% enrollment rate); 320 completed two or more days of symptoms (median age=65.6 [range 18.8-93.2]; 43.8% female). The most common cancers were gastrointestinal (36.9%), lung (18.8%), and genitourinary (12.2%). Nearly half of patients (48.5%) had one or more comorbid conditions in addition to cancer. We found no significant differences between intervention and usual care regarding the proportion of days with improved ESAS total (B=-0.05, P=.17), ESAS physical (B=-0.02, P=.52), PHQ4 anxiety (B=-0.03, P=.33), and PHQ4 depression (B=-0.02, P=.44) symptoms. Intervention patients also did not differ from usual care with respect to secondary endpoints of hospital LOS (7.50 v 7.59 days, P=.88) and readmission rates within 30 days of discharge (32.5% v 25.6%, P=.18). Conclusions: For hospitalized patients with advanced cancer, this symptom monitoring intervention did not have a significant impact on their symptom burden and health care use. These findings do not support the routine integration of this type of symptom monitoring intervention for hospitalized patients with advanced cancer. The positive outcomes seen in previous studies of symptom monitoring interventions may not be reproduced in other patient populations and care settings. Support: UG1CA189823; Clinical trial information: NCT03396510 .