bluuebunny/crossref_metadata_2025 huggingface dataset:
Remote delivery of a mindfulness-based intervention to decrease stress levels and promote coping among health-care workers during the COVID-19 pandemic.
Authors: Helou Joelle Antoine , Barry Aisling S , Ye Philip , Liu Fei-Fei , Julius Anet , Letourneau Daniel , Wong Philip , Dawson Laura A. , Elliott Mary
Published: June 2023

11007

Background: The COVID-19 pandemic has caused significant stress amongst everyone around the world. Healthcare workers (HCW) in particular, experience substantial stress in these challenging environments. In an effort to find supportive interventions for radiation oncology providers, while respecting the requirements of physical distancing, we proposed the remote delivery of a mindfulness-based intervention (MBI). The primary aim of this study is to determine the association of this intervention with a reduction of perceived stress. Secondary aims are to evaluate the impact on coping and burnout amongst HCW in the Radiation Program (RP). Methods: This is a single-centre, single-arm, pilot study. All HCW associated with the RP were eligible. This was a voluntary effort. The intervention - manualized, mindfulness-based group for HCW, entitled Mindfulness-Based Resilience and Well-Being Training, consisted of four 1-hour sessions per week for 4 weeks. From Nov 2020 to Dec 2021, 6 consecutive closed groups MBI were delivered remotely using Zoom. Each group consisted of 5-12 participants and one professional with a background in mindfulness facilitation. The Perceived Stress Scale (PSS), The Maslach Burnout Inventory and the BriefCOPE questionnaire were collected pre-intervention, and at 1, 4 and 12 weeks post-intervention. Linear mixed effect models with a random intercept to account for the repeated measures were used to assess the change of outcomes over time. Results: Amongst 43 HCWs who expressed initial interest, 33 completed the study. At 1-, 4- and 12-weeks post-intervention 25, 24 and 21 participants provided completed questionnaires respectively. Time constraint was the main reason for withdrawal and missing data. There was a significant decrease in perceived stress at week 1, 4 and 12 when compared to baseline [mean baseline PSS score: 22.5 (SD = 4.6), week 1: 18.4 (4.9), p= 0.002, week 4: 16.8 (6.5), p< 0.001, week 12: 16.3 (6.8), p< 0.001]. Overall, 7 (21%) participants reported high PSS (27-40) at baseline while none reported high levels at 1 and 12 weeks. Problem focused coping( p= 0.02), and active coping ( p= 0.009) were significantly higher at 1 week but not at 4 and 12 weeks. Conclusions: The remote delivery of a MBI is feasible and effective to reduce perceived stress levels and to promote coping across HCWs. These findings need to be validated in a larger cohort. Time was a major constraint preventing the participation of interested HCWs. It would be extremely valuable for departments to support such interventions and programs to help HCWs cultivate skills to meet the demands related to working in healthcare environments throughout and beyond this crisis.
Assessment of YouTube as an information source for immune checkpoint inhibitors (ICIs).
Authors: Garg Tulika , Chahal Rutvi , Khosla Atulya Aman , Singh Rohit , Karass Susan Hosny , Sharma Rakesh Kumar , Roy Arya Mariam , Thakkar Astha , Jatwani Karan
Published: June 2023

11009

Background: YouTube is an open-access source of information. With more than 2.5 billion users, it can play a pivotal role in educating or misinforming cancer patients. ICI has changed the treatment paradigm for cancer over the past decade. There is scarce data to evaluate the quality of information on ICI uploaded on YouTube. We aim to assess the quality and engagement parameters of the 100 most viewed videos on YouTube focusing on ICI. Methods: A systematic search was conducted on YouTube using the search terms (“Immunotherapy AND Cancer”; “Immune Checkpoint Inhibitors AND Cancer”). The 100 most viewed English videos were selected. We utilized the already validated PEMAT1 and DISCERN2 tools to assess the quality of these videos on ICI. Additionally, we looked at the number of views, comments, and likes. Descriptive statistics and Pearson correlation tests were performed using R studio v2022.12.0-353. Results: The videos in our study had up to 42 million views (median views: 17,617). These videos were categorized by sources; academic (54%), media (31%), and industry (15%). The mean DISCERN score for the videos was 43.4. Only 22% videos were in the good or excellent category. Most videos (53%) discussed the benefits of ICI, whereas only 29% discussed the adverse effects of ICI. Shared decision-making was promoted by 34% of videos, and only 6.7% of videos summarized the information at the end, based on the DISCERN criteria. The medical terminologies were defined by 48.5% of videos, and 31% were broken into short sections with informative headers per PEMAT understandability criteria. There was no significant association between the video source and video engagement parameters, including likes, views, and comments. However, a trend towards an increased number of likes (r=-0.195, p=0.04) and comments (r=-0.213, p=0.03) was noticed with lower DISCERN scores (poor quality videos). Conclusions: The majority of YouTube videos are focused on the benefits of ICI. They are less likely to discuss the adverse effects or shared decision-making . In summary, YouTube videos contain biased information on ICI. Further efforts from academic institutions are needed to improve the quality and engagement of these videos. 1. Shoemaker SJ et al. The Patient Education Materials Assessment Tool (PEMAT) and User’s Guide; 2. Charnock D et al. DISCERN: an instrument for judging the quality of written consumer health information on treatment choices. J Epidemiol Community Health. 1999. Pearson correlation coefficient (r) between quality assessment scores and video variables. [Table: see text]
Defining the educational needs for a community-based hematology/oncology career: A national needs assessment.
Authors: Agrawal Shubham , Patell Rushad , Dodge Laura E. , Pegher Jennifer W , Coleman Robert L. , Waterhouse David Michael , Roberts Daniel Aaron , Rangachari Deepa
Published: June 2023

11011

Background: Fellowship training is largely rooted in academic medical centers, though many graduates will ultimately pursue careers in community-based settings. We initiated a national survey of hematologists/oncologists practicing in community or academic-community hybrid settings to understand providers’ educational needs. We hypothesized that the current model of fellowship training is not optimized for those pursuing community-based hematology/oncology careers. Methods: An electronic questionnaire was developed surveying current attitudes and practices of community-based hematologists/oncologists. Survey participants from across the United States were contacted via professional organizations. We primarily assessed whether survey participants received any specific training during fellowship for community-based practice. Participants were also surveyed regarding whether such training may have affected their preparation. Relative risk (RR) and 95% confidence intervals (CI) were calculated using modified Poisson regression with robust error variance adjusted for: time in clinical practice ( < 10 years), size of graduating fellowship training program ( > 5), board certification (hematology and oncology vs. either), and training program geographic location (by region) to identify factors associated with receiving community oncology-specific training. Results: Of the preliminary cohort of 120 participants from across 25 states, 66% were male, 69% identified as White, and 69% had been in practice for > 10 years. Less than half (43.2%, binomial 95% CI 34.6%-52.2%) received any training for a career in a community-based setting. Participants identified rotations in community settings (48%), direct mentorship from community-based physicians (41%), and longitudinal clinic in a community setting (39%) as experiences that would have been valuable. Specific curricula of interest included: medical operations and administration (67%), health policy (38%), and quality improvement (30%). Respondents in clinical practice for < 10 years were more likely to have received any community oncology-specific training (RR 2.02, 95% CI 1.10–3.72); other factors were not significantly associated with the primary outcome (P > 0.05). Conclusions: National trends indicate a growing need for hematology/oncology graduates in community-based settings. Our study demonstrates substantial unmet needs as they relate to training fellows destined for careers in community-based practice. Prospective design of clinical training and curricula emphasizing longitudinal exposures to and key aspects of health care delivery in the community setting are paramount to achieving optimal, goal-concordant hematology and oncology training.
Early introduction to clinical radiation oncology through a self-directed competency-based medical student curriculum.
Authors: Claunch Cheryl , Dalwadi Shraddha , Wang Jarey , Ludwig Michelle Suzanne
Published: June 2023

11038

Background: Specialty training is not traditionally incorporated into standard medical education and there is a deficiency in exposure to Radiation Oncology for “last minute” interested candidates, particularly from underrepresented backgrounds. Therefore, we implemented MERAO-200, an introductory 2-week in-person and virtual medical education curriculum without clinical prerequisites to facilitate early introduction to the field of Radiation Oncology and report its effect on student comfort and familiarity with radiation planning and contouring. Methods: Clinical students were enrolled in a 2-week elective without clinical prerequisites that integrated both clinical activities and self-directed learning through virtual contouring modules. The virtual curriculum was designed around three modules available on EduCase. A survey was conducted after completion of the modules that solicited self-identifying information and to assess their efficacy in increasing understanding of basic contouring skills. Paired t-tests were used to compare pre- and post-elective assessment results. Results: Twenty-three total students have completed MERAO-200 from Fall 2020 to Spring 2023. Of those, 15 submitted the survey. Eight (53%) students did not answer self-identifying information such as gender, race, ethnicity, or country of origin. Four (27%) students identified as Asian and 3 (20%) as white. No students identified as Hispanic, Latino or Spanish origin. Seven (46%) students identified as having USA as country of origin. Seven (47%) students reported interest in radiation oncology, medical oncology or surgical oncology. Three (20%) students were MS2, 7 (47%) were MS3, and 5 (33%) were MS4. Overall, there was a significant increase in comfort level using radiation planning software (p = 1.1e-4) as well as ability to find relevant contouring references (p = 4.2e-5). Knowledge of the anatomy and contouring principles also improved for the three modules: eye and brain (p = 2.8e-7), high grade glioma (3.2e-6), and head and neck nodal stations (4.5e-6). CNS module difficulty on a scale of 1-10 had a median difficulty score of 7 (range 3-8) and head and neck module difficulty was a median of 7 (range 3-10). Conclusions: Implementation of MERAO-200 improved medical student exposure to the field of Radiation Oncology and improved medical student comfort and familiarity with radiation planning and across all disease sites covered. More outreach work needs to be done to facilitate inclusion of minority student populations and students from underrepresented backgrounds. Early introduction at the medical student level could be a pathway to improve disparity in the field of Radiation Oncology.
Efficacy and safety of nivolumab and trabectedin in pretreated patients with advanced soft tissue sarcomas (STS): Results of a phase II trial of the German Interdisciplinary Sarcoma Group (GISG-15, NitraSarc).
Authors: Reichardt Peter , Andreou Dimosthenis , Flörcken Anne , Groß Thorben , Richter Stephan , Kessler Torsten , Kortüm Martin , Schmidt Christian Andreas , Kasper Bernd , Wardelmann Eva , Benedict Atzler , Sookthai Disorn , Mueller Daniel Wilhelm , Pink Daniel
Published: June 2023

11500

Background: Programmed death-1 (PD-1) inhibitors alone have modest activity in the treatment of most STS. A possible synergistic effect of combined trabectedin with PD-1 inhibitor nivolumab has been previously reported. Herein we evaluated the efficacy and safety of trabectedin plus nivolumab as a second-line treatment of patients with anthracycline-pretreated metastatic or inoperable STS. Methods: The prospective, explorative, two-group, non-randomized phase II NiTraSarc trial enrolled patients with advanced lipo- or leiomyosarcomas (Group A; GA) or with non-L-sarcomas (Group B; GB). Patients were initially treated with 3 cycles of trabectedin 1.5 mg/m2, followed by the combination of trabectedin 1.5 mg/m2 plus nivolumab 240 mg in a so-called “late combination cohort” (LCC) for up to 16 cycles. After positive results of a preplanned interim analysis, patients received the combination therapy already starting from Cycle 2 in an “early combination cohort” (ECC). Primary efficacy endpoint was progression-free survival rate after 6 months (PFSR6) according to RECIST v.1.1. A central pathological assessment (CPA) was done from tumor specimen from all patients. Updated results according to cpa are presented. Results: A total of 92 patients were recruited in the trial: 43 patients in GA and 49 in GB. In GA, 28 patients (63%) had leiomyosarcoma and 15 (37%) had liposarcoma. Most common sarcoma types in GB were pleomorphic (n = 12), spindle cell (n = 11), fibromyxoid (n = 6), synovial (n = 5) and epithelial (n = 4) sarcoma. After median follow up of 16.6 months, overall PFSR6 as per CPA in GA was 47.6% (60% in LCC vs 36.4% in ECC) and 14.6% in GB. Median PFS was numerically higher in GA compared to GB (5.5 vs 2.3 months) and even longer in LCC vs ECC (9.8 vs 4.4 months). Median overall survival was more than three times longer in GA vs GB (18.7 vs 5.6 months) and, again, longer in LCC vs ECC (24.6 vs 13.9 months). Safety trabectedin and nivolumab was consistent with the safety profiles of each drug alone with no relevant new findings for the combination or between LCC and ECC. Conclusions: Our study confirms the activity of trabectedin plus nivolumab, particularly in patients with lipo- or leiomyosarcomas. There is a significant difference between ECC and LCC in terms of PFSR6, PFS and OS. The results in patients with non-L-sarcomas do not justify further investigation of this combination. Clinical trial information: NCT03590210 .
The clinical value of tumor-informed minimal residual disease detection in sarcoma.
Authors: Fu Yiwei , Shen Jingnan , Huang Gang , Zou Changye , Xie Xianbiao , Shi Xiaoliang , Jian Qijie , Huang Jintao , Pang Fei , Yin Junqiang
Published: June 2023

11510

Background: The high recurrence and metastasis rates lead to poor survival of patients with sarcoma. At present, circulating tumor DNA-based minimal residual disease (MRD) has been studied in varies solid tumors and proved to be valuable in guiding treatment and predicting recurrence, but its application in sarcomas is rarely reported. Methods: Tumor tissue samples were used for whole exome sequencing (WES) and clonal mutations were selected for the customized MRD panel. Blood samples were collected for MRD detection. Experiments were conducted at OrigiMed, a College of American Pathologists accredited and Clinical Laboratory Improvement Amendments certified laboratory. Results: A total of 84 sarcoma patients including 47 bone tumor (BT), 32 soft-tissue sarcoma (STS), and 5 undifferentiated small round cell sarcoma (USRCS) patients were enrolled. Patients consisted of 49 (58.3%) males and 35 (41.7%) females, with a median age of 23 years old (1-85 years old). Based on WES, we found that 64% (4936/7715) of the mutated genes were unique to each patient, and 70.4% (859/1220) of selected tumor-informed single nucleotide variants (SNV) were variants with unknown significance, suggesting that tumor-informed MRD is superior to panel-based MRD in sarcomas. In this cohort, 78.6% (66/84) of patients successfully constructed MRD panels, including 85.1% (40/47) of BT patients, 75% (24/32) of STS patients, and 40% (2/5) of USRCS patients. The main reason for failure was the scarcity of SNVs detected. Preoperative MRD detection was performed on 6 cases and revealed a positive rate of 100%. MRD detection was performed twice on 2 patients during preoperative neoadjuvant therapy. For the patient with constant allele frequencies detected throughout the treatment course, imaging showed tumor enlargement; While for another patient with a trend of reduction in allelic frequency, imaging showed tumor shrinkage and necrotic tumor tissue was observed in surgery one month later. These two patients had not recurred after surgery at the time of analysis. Post-surgery MRD detection were performed on 27 patients, of which 1 STS and 7 BTs were positive (30%, 8/27). Three of them confirmed recurrence by imaging at 12, 30, and 101 days after detection of positive MRD, respectively. However, there were still no imaging recurrence in the other patients so far, including the 5 remaining patients with positive MRD and 19 patients with negative MRD. Follow-up is still ongoing. Conclusions: MRD tests had been successfully performed in most of the sarcoma patients. Due to the heterogeneity of sarcomas, about 64% of mutated genes of sarcomas are unique individually, which may be more suitable for monitoring with tumor-informed MRD panel. Tumor-informed MRD could be used to predict the efficacy of preoperative neoadjuvant therapy and discover recurrence earlier than imaging in sarcoma.
Deep learning with whole slides images to predict histological response to neoadjuvant chemotherapy in patients with resectable high grade soft-tissue sarcomas: A multicenter study.
Authors: Adjadj Benjamin , Schutte Kathryn , Maussion Charles , Jean-Denis Myriam , Karanian Marie , Coindre Jean Michel , Italiano Antoine
Published: June 2023

11512

Background: Two recent randomized trials have confirmed the potential benefit of neoadjuvant anthracycline-based chemotherapy in patients with high-grade soft-tissue sarcomas (STS) (Issels et al 2018, Gronchi et al 2017). However, as for adjuvant chemotherapy, the main issue with neoadjuvant treatment of STS patients is the identification of predictive factors of response to chemotherapy that could avoid for a majority of patients ineffective and potentially toxic treatment with impaired quality of life. Histological response, defined as the percentage of stainable tumor cells on the surgical specimen, has been shown to be a reliable surrogate for metastasis-free survival and overall survival in bone but also in soft-tissue sarcomas (Crombe et al JCO Clin Inf 2021). Developing a tool to help medical oncologists predict the potential benefit of neoadjuvant chemotherapy prior to starting the treatment would be of great value for precision medicine in sarcomas. To address this need, we propose a deep learning-based approach to predict histological response to neoadjuvant chemotherapy patients from routine histological whole slide images sampled at diagnosis. Methods: A cohort of 220 patients with high grade limb and trunk wall STS enrolled in the NEOSARCOMICS study (NCT02789384, sponsor: Institut Bergonié, Bordeaux, France) was used to train a model to predict the binarized histological response from diagnostic biopsies. Responders are defined by a histological response inferior or equal to 10%. Digitized hematoxylin/eosin slides were preprocessed to segment the tissue and decompose the image into patches of smaller resolution. Features were extracted from each patch using a Vision Transformer pretrained in a self-supervised fashion on histology slides. A Multiple Instance Learning model was trained on the resulting features to compute a prediction at the patient level. The algorithm was trained and validated through a 5-fold, 5-repeat cross-validation scheme. Finally, external validation is performed on an unseen cohort from Centre Léon Bérard to assess the robustness of the model. Results: To predict histological response to neoadjuvant chemotherapy, a model using only diagnostic biopsies achieved an AUC of 0.69 (95% confidence interval, 0.60-0.76). External validation is ongoing and shows promising preliminary results with an AUC of 0.67 (95% confidence interval with bootstrapping, 0.45-0.89). Conclusions: This multi-center study demonstrates that deep-learning models can accurately predict the histological response to neoadjuvant chemotherapy from routine histological whole slide images sampled at diagnosis. This model could be used as a pre-screening tool to improve patient selection for neoadjuvant chemotherapy in STS.
A phase II basket trial of dual anti–CTLA-4 and anti–PD-1 blockade in rare tumors (DART) SWOG S1609: The desmoid tumors (cohort 27).
Authors: Chae Young Kwang , Othus Megan , Patel Sandip Pravin , Powers Benjamin , Hsueh Chung-Tsen , Govindarajan Rangaswamy , Bucur Silvana Z. , Chung Liam Il-Young , McLeod Christine , Chen Helen X. , Sharon Elad , Streicher Howard , Ryan Christopher W. , Blanke Charles David , Kurzrock Razelle
Published: June 2023

11516

Background: Dual inhibition with Anti-PD-1 and anti-CTLA4 checkpoint inhibitors is efficacious in many malignancies, but their potential role in numerous rare solid cancers is yet to be established. Desmoid tumors (DT; fibromatosis) are rare tumors of the soft tissue, and the mainstay of treatment is surgery (Richard Riedel, 2022). The utility of immunotherapy in this group of patients has not been explored. This study presents the first results of ipilimumab and nivolumab used in the DT cohort (#27) of the SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART) trial. Methods: DART is a prospective, open-label, multicenter/multi-cohort phase 2 clinical trial of ipilimumab (1mg/kg intravenously every 6 weeks) plus nivolumab (240mg intravenously every 2 weeks). The primary endpoint includes objective response rate (ORR) (RECIST v1.1) (confirmed complete (CR) and partial responses (PR)). Secondary endpoints include progression-free survival (PFS), overall survival (OS), stable disease (SD) > 6 months, and toxicity. Results: Sixteen evaluable patients (median age 37) with desmoid tumors were analyzed. Location of the tumors are: 8, abdomen; 3, lower limb: 2, upper limb; 2, pelvis; and 1, neck. ORR was 18.8% with 3 patients attaining PR: 40% regression with ongoing duration of response (DoR) at over 30+ months; 83% regression (PFS 16 months); and 71% regression (PFS of 8.4 months). Of note, 3 patients had SD (3/16, 18.8%) with some shrinkage of the tumors and a durable response; 23% regression with PFS of 1820+ days; 6% regression with PFS of 902 days; 1% regression with PFS of 1147+ days. Overall clinical benefit rate (CBR; no progression > 6 months) was 62.5%. The median PFS was 17.9 months, 6-month PFS 69%, 1-year PFS 62%. All patients were alive at 1 years; median OS was not assessable as 14 patients are showing ongoing survival. The most common adverse events were fatigue (43.8%, n = 7), nausea (37.5%, n = 6), hypothyroidism (31.3%, n = 5), diarrhea, hyperthyroidism, headache, and adrenal insufficiency (25%, n = 4 each). There were 8 incidents (50%) of grade 3-4 adverse events. 7 adverse events led to discontinuation. There were no grade 5 adverse events. Conclusions: Ipilimumab plus nivolumab in treatment of desmoid tumors resulted in an ORR of 18.8% and CBR of 62.5% with durable responses seen. This is the first prospective study demonstrating efficacy of the combination in this rare disease. Correlative studies to determine response and resistance markers are ongoing. Expanded prospective studies in desmoid tumors are needed. Clinical trial information: NCT02834013 .
Results from phase I/II study of NY-ESO-1-specific TCR gene-transduced T cell therapy (TBI-1301, mipetresgene autoleucel) in patients with advanced synovial sarcoma.
Authors: Kawai Akira , Ishihara Mikiya , Nakamura Tomoki , Kitano Shigehisa , Iwata Shintaro , Takada Kohichi , Emori Makoto , Kato Koji , Endo Makoto , Matsumoto Yoshihiro , Kakunaga Shigeki , Sato Eiichi , Miyahara Yoshihiro , Morino Kunihiko , Tanaka Shinya , Takahashi Shuichi , Matsumine Akihiko , Kageyama Shinichi , Ueda Takafumi
Published: June 2023

11558

Background: Synovial sarcoma is one of malignant soft tissue tumors with a poor prognosis. A cancer-testis antigen NY-ESO-1 is expressed in the tumors of 50-80% synovial sarcoma patients. The purpose of this study was to evaluate the safety and the efficacy of gene engineered autologous T cell product with NY-ESO-1 siTCR retroviral vector which expressed affinity-enhanced NY-ESO-1-specific TCR and siRNA to silence endogenous TCR (TBI-1301). Methods: This was an open label phase I/II study to evaluate safety, appearance of replication competent retrovirus (RCR), appearance of clonality, in vivo cell kinetics and clinical responses. TBI-1301 were manufactured from each subject’s leucocytes stimulated with anti-CD3 antibody and Retronectin and transduced with NY-ESO-1 siTCR retroviral vector. TBI-1301 was infused at split dose of 5 x 109 cells following cyclophosphamide treatment at 750 mg/m2 for two days to HLA-A*02:01 or HLA-A*02:06 positive subjects with synovial sarcoma expressing NY-ESO-1, which were surgically unresectable and refractory to anthracycline therapy. Results: Eight subjects were enrolled and treated with TBI-1301. The objective response rate was 50.0% with best overall partial response in 4 of 8 subjects according to RECIST v1.1/irRECIST and the median overall survival was 650 days. Cytokine release syndrome (CRS) occurred in 50.0% (4/8) and consisted of 1 subject with grade 1 CRS and 3 subjects with grade 2 CRS. All subjects who developed CRS recovered with prespecified treatment, in which 2 subjects were treated with symptomatic therapy, 1 subject was treated with tocilizumab and 1 subject was treated with both tocilizumab and corticosteroid. No subjects had immune effector cell- associated neurotoxicity syndrome (ICANS). RCR and clonal dominance were not detected in any subjects throughout the study period. Conclusions: Adoptive immunotherapy with TBI-1301 to selectively target NY-ESO-1 positive tumors will become a promising treatment for advanced or recurrent synovial sarcoma with acceptable toxicity. Clinical trial information: NCT03250325 .
Evaluation of hyperprogression in patients with sarcoma treated with targeted therapy and/or immunotherapy in early-phase clinical trials.
Authors: Alshibany Aisha , Al-Ezzi Esmail Mutahar , Gupta Abha A. , Salawu Abdulazeez , Watson Geoffrey Alan , Wang Lisa , Bedard Philippe L. , Spreafico Anna , Hansen Aaron Richard , Siu Lillian L. , Abdul Razak Albiruni Ryan
Published: June 2023

11560

Background: Hyper-progressive disease (HPD) is an adverse outcome with acceleration of tumor growth, often accompanied by clinical deterioration. This phenomenon is described with immunotherapy (IT) but its incidence in sarcoma and/or in the context of targeted therapy (TT) remains unknown. Tumor growth rate (TGR) allows for dynamic evaluation of tumor volume change over time and may complement RECIST. We evaluated HPD in sarcoma patients (pts) treated in early-phase trials by assessing TGR and describing their subsequent clinical outcomes. Methods: We retrospectively reviewed medical records from advanced soft tissue sarcoma (STS) pts enrolled in early phase trials at the Princess Margaret Cancer Centre between January 2012 and December 2022. TGR was calculated based on tumor measurements taken at pre-baseline, baseline, and on-treatment CT scans. We used the Champiat formula (Clin Cancer Res 2017) to calculate TGR ratio. Primary objective was to describe the incidence of HPD, defined as a TGR ratio of > 50%. Secondary objective was to investigate the correlation between HPD with progression-free survival (PFS) and overall survival (OS). Results: We identified a total of 192 pts involved in STS early phase trials from 2012-2022. Most common histology was leiomyosarcoma seen in 72 pts. Eighty-four pts (43.8%) received TT, 75 (39%) pts received IT-based, and the rest had combined TT/IT regimens (n = 33, 17.2%). The incidence of HPD was 6.8% (n = 13), including IT-based (n = 9) and non-IT-based (n = 4) regimens. HPD was associated with a worse PFS, and OS compared to non-HPD pts (median PFS 1.6m vs 4.6m HR: 5.5, 95%CI 2.8-10.6, P < 0.001; median OS 5.5 vs 16.1 months; HR: 3.7, 95%CI: 2.0-7.1, P < 0.001). On multivariable analysis, only IT was significantly associated with HPD (OR 3.9, 95%CI: 1.1-13, P = 0.021). There was no association between HPD and new lesions or sarcoma histology subtype. Conclusions: HPD occurs in a small subset of sarcoma patients undergoing clinical trials with TT or IT. Exploring TGR provides clinically meaningful data as it pertains to HPD as it predicts OS and PFS in sarcoma patients undergoing early-phase clinical trials.
Web-based patient-reported outcome measures (PROMs) in elderly cancer patients: A French multicentric prospective feasibility trial (the FASTOCH study).
Authors: Cancel Mathilde , Sauger Carine , Biogeau Julie , Dardaine Véronique , Lecomte Thierry , Deloigne Amandine , Hebrard Philippe , Wilmet Rémy , Solub David , Christiann François , Laplaige Philippe , Combe Pierre , Dorval Etienne
Published: June 2023

12011

Background: Web-based PROMs in cancer care improve overall survival and quality of life. There is, nonetheless, no data available on this type of follow-up in the elderly population. Methods: From February 2021 to April 2022, 75 or more years-old patients ongoing any active anti-cancer treatment (such as chemotherapy, targeted therapy, hormonotherapy, immune therapy) were included, in six French cancer centers. Feasibility of the web-based PROMs was assessed as the part of the population included that could use the Ana-Health’s web-based application “ANA” to monitor their symptoms, the others being considered as in “primary failure” due to technological barriers or refusal to participate. Among the patients that agreed to participate, we then defined as “active” those who filled at least one form during the three months follow up. We also searched for factors restraining elderly patients to use “ANA” and evaluated their satisfaction. Results: Overall, 473 patients were included in the study. There were 288 patients in “primary failure” (233 without Internet access, 17 not comfortable enough to use web-based PROMs, 38 refusals to participate). Among the 185 patients “willing to participate”, there were 122 “active” patients and 63 “inactive” ones, leading to a 26% feasibility in intention-to-test and a 66% feasibility in per protocol analysis. Patients “willing to participate” were from higher socio-professional category (p = 0.002) and had a significantly higher G8 score (13.5 versus 12, p < 0.001), particularly when considering the autonomy (p = 0.028), cognitive assessment (p = 0.003) and general condition (p < 0.001) items. In the multivariate analysis, the socio-professional category and the general condition were still significantly different (p = 0.009 and 0.002 respectively). The only factor that remained significantly different between the “active” and “inactive” populations was the better general condition in the “active” group (p < 0.001). The “inactive” patients prematurely ended their participation because they lost interest in the web-based follow up significantly more than the “active” group (28 “inactive” patients, i.e. 44%, vs 5 “active” patients, i.e. 4%, p < 0.001). Similarly, the “active” patients were significantly more satisfied with “ANA” than the “inactive” (71% vs 29%, p < 0.001). Conclusions: Our study shows that, in the elderly population treated for a cancer, a web-based application to measure PROs is feasible, however socio-professional category, general condition and above all technological barriers are of some concern.
Association of emotional support with quality of life, mental health, and survival among older adults with gastrointestinal (GI) malignancies.
Authors: Clausing Daniel , Fowler Mackenzie Elisha , Harmon Christian , Outlaw Darryl Alan , Akce Mehmet , El-Rayes Bassel F. , Giri Smith , Williams Grant Richard
Published: June 2023

12050

Background: Emotional support (ES) is the most frequently reported support need among older adults with cancer. Yet, the association of ES with cancer outcomes is largely unknown. This study examined the association of ES with health-related quality of life (HRQoL), mental health, and survival among older adults with GI malignancies. Methods: We included older adults (≥60y) newly diagnosed with GI cancer and undergoing a self-reported geriatric assessment (GA) at first clinic visit. Self-reported ES, measured by the Medical Outcomes Survey was the primary exposure. Outcomes included physical and mental HRQoL as measured by the Patient-Reported Outcomes Measurement Information System® (PROMIS) 10-item global assessment, anxiety and depression as measured by the PROMIS Anxiety and Depression Short Form 4a, respectively, and one-year, two-year, and overall survival. Linear regression evaluated the association between ES and t-scores of physical/mental HRQoL. Logistic regression evaluated the association of ES with anxiety and depression. Models were adjusted for age, race, sex, and cancer type/stage. Kaplan-Meier curves and log-rank tests evaluated the association between ES and survival outcomes. Results: Overall, 795 participants were included. The median age was 68 (IQR: 64-74) and patients were 58.0% male, and 74.6% White. The most common cancers included colorectal (37.9%) and pancreatic (30.8%), with mostly advanced staged disease (Stage III/IV: 72.1%). A majority (77.6%) had adequate ES. Patients with inadequate ES were more likely to be Black (31.5 vs. 20.8%, p=0.005), disabled (24.1 vs. 10.4%, p<0.001), and widowed/divorced (54.2 vs. 24.8%, p<0.001). After adjustment, patients with inadequate ES had lower physical and mental HRQoL t-scores (Physical β: -3.35, 95% CI: -5.25, -1.46; Mental β: -2.46, 95% CI: -4.11, -0.81) and higher odds of depression (aOR: 2.22, CI: 1.34-3.69). There was no statistically significant association with anxiety (aOR:1.15, CI: 0.73, 1.81). No differences were observed between patients with inadequate versus adequate ES in one-year, two-year, or overall survival (Log-Rank tests: one-year, p=0.952; two-year, p=0.606; overall, p=0.584). Conclusions: Older adults with inadequate ES have higher odds of poor physical and mental HRQoL and depression, but no difference in survival compared to those with adequate ES. Further work is necessary to determine if interventions to improve ES also improve HRQoL and depression.
Safety of checkpoint inhibitors in older patients with genitourinary cancers.
Authors: Ramnaraign Brian Hemendra , Patel Neil Jigish , Chatzkel Jonathan Alexander , Hitchcock Kathryn , Zlotecki Robert , O'Malley Padraic , Crispen Paul
Published: June 2023

12059

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the care of patients with genitourinary (GU) cancers however many of the clinical trials that have led to the approval of ICIs in GU cancers often have low enrollments of older patients aged 65 and above for which safety data in this cohort is limited. Methods: A retrospective study was performed that included all patients aged 65 and older with kidney, bladder, and upper tract urothelial carcinoma (UTUC), who were treated at the University of Florida Health Cancer Center between January 2018 and September 2022, and received at least one dose of ICI (pembrolizumab, nivolumab, ipilimumab with nivolumab, avelumab, or atezolizumab). Data was collected on all documented immune related adverse events (irAEs) that were deemed attributable to the checkpoint inhibitor by the treating provider. The grading of toxicities was determined by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: We identified a total of 139 patients who met the inclusion criteria of our study. The ages of patients ranged from 65 to 93 and the median age was 74. Females accounted for 31 patients (22%) while 108 patients (78%) were male. There were 56 patients (40%) with bladder cancer, 58 patients (42%) with kidney cancer, and 25 patients (18%) with UTUC. An irAE was documented in 76 patients (55%) while 63 patients (45%) had no documented irAE. Patients were categorized by the highest grade of toxicity experienced. A Grade 1 toxicity was found in 15 patients (11%), while a grade 2 toxicity was found in 41 patients (29%), with 18 patients (13%) having a grade 3 toxicity, and 2 patients (1%) experiencing a grade 4 toxicity. There were no documented grade 5 toxicities, i.e. no deaths were directly attributed to treatment. We found that 27 patients (19%) required either oral or intravenous steroids to manage their irAE. Discontinuation of treatment due to an irAE was observed in 16 patients (12%). Inpatient hospitalization due to an irAE occurred in 12 patients (9%). Conclusions: Our study demonstrates that the majority of patients aged 65 and older either have no irAEs or developed mild irAEs when treated with ICIs. Severe and life-threatening adverse events are uncommon, rarely require hospital admission, and did not lead to any deaths. This study should help to provide valuable information on the safety of checkpoint inhibitors in older patients with GU cancers and assist in the shared decision-making process for cancer treatment. [Table: see text]
Nutritional program among patients with prostate cancer receiving androgen deprivation therapy (ADT).
Authors: Lages Dr. Paulo Sergio , Vargas Pivato de Almeida Daniel , Bergerot Cristiane Decat , Bergerot Paulo Gustavo , Barbosa Michelle , Dutra Camila Rosa
Published: June 2023

12072

Background: Treatment with ADT can lead to changes in body composition, including an increase in body fat and a decrease in muscle mass. To minimize the nutritional risks associated with ADT, a nutritional program was developed. Thus, this study sought to determine the benefit of this program among patients with prostate cancer receiving ADT. Methods: Patients were recruited in a cancer center located in Brasilia, Brazil. Patients were eligible if they were diagnosed with prostate cancer, and about to initiate treatment with ADT. They were assessed before starting ADT and at follow-up assessment (3 months). Based on their risk, patients were instructed to follow either a normocaloric (20-25 kcal/kg) or a hypocaloric (18-20 kcal/kg) diet, and both groups were required to consume a hyperproteic diet (1-1.2 g/kg), including the use of whey protein supplementation as needed. Outcomes measures included nutritional risk (Patient-Generated Subjective Global Assessment; PG-SGA), body composition (Medical software Lookin’Body120), and muscle strength (Jamar Hydraulic Hand Dynamometer). Descriptive statistics were generated, and paired T-test, Wilcoxon signed rank on paired samples and ANOVA-RM were used to evaluate changes in variables over time. Results: A total of 62 patients were included in this program. Participants had a median age of 75 years (range from 41-97) and were predominantly married (87%). A great proportion of patients (65%) were diagnosed with a stage IV disease. Notably, 23% were diagnosed with moderate to severe nutritional risk at baseline; 47% were overweight, 13% were obese and 14% were with sarcopenia. The nutritional program resulted in maintenance of total body weight (median 74.1 vs 75.6 kg, P=0.12), lean body weight (median 29.1 vs 29.4 kg, P=0.11), and muscle strength (median 30 vs 30 kg, P=0.62), while a statistically significant loss of body fat weight (median 22.0 vs 20 kg, P=0.003) was found over the 12-week period. Despite no change in the PG-SGA scores were noted overtime, the rate of sarcopenia has decreased (15% vs 13%, P=0.03) and the proportion of eutrophic patients has increased (18% vs 27%, P=0.001), as seen in the contingency table below. Conclusions: These findings suggest that this program may improve body composition and maintain muscle strength in men receiving treatment with ADT after only three months of intervention. Future studies should validate the benefit of this program in randomized trial with a longer follow-up assessment (6 and 12 months after treatment initiation). [Table: see text]
Impact of exercise on chemotherapy-induced peripheral neuropathy (CIPN) in survivors with post-treatment primary breast cancer.
Authors: Saint Kirin , Lessing Alexie , Nemirovsky David , Chen Yuan , Underwood Whitney P. , Galantino Mary Lou , Jones Lee , Bao Ting
Published: June 2023

12077

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of neurotoxic chemotherapy with limited treatment options. We examined the association between exercise and CIPN symptoms in patients with post-treatment primary breast cancer. Methods: Using a retrospective design, patients completing a standardized survey assessing exercise exposure, neuropathy symptoms, and pain in a tertiary cancer center survivorship clinic were included. Exercise was assessed using a standardized questionnaire quantified in standardized metabolic equivalent tasks (MET-h/wk). Chi-square tests, Mann-Whitney U-tests, Kendall’s rank correlations, and multivariable logistic regressions adjusting for important clinical covariates examined the relationship between exercise and CIPN and whether this differed as a function of chemotherapy regimen (taxane vs. non-taxane based therapy). Results: A total of 5,444 patients with primary breast cancer previously treated with adjuvant chemotherapy (median age 62 years (IQR: 55, 71); median of 4.7 years post chemotherapy completion (IQR: 3.3, 7.6)) were identified. The overall prevalence of CIPN was 34% (95% CI: 33%, 36%); 33% (95% CI: 31%, 34%) for non-taxane and 37% (95% CI: 35%, 39%) for taxane based chemotherapy. The prevalence of CIPN was 28% (95% CI: 26%, 30%) among exercisers (≥5 days of moderate or ≥3 days of strenuous exercise per week) and 38% (95% CI: 37%, 40%) among non-exercisers (difference 11%; 95% CI: 8%, 13%; p < 0.001). Associations appeared dose-dependent. CIPN prevalence was 42% for < 6 MET-h/wk, 33% for 6-20.24 MET-h/wk and 29% for > 20.25 MET-h/wk (p-value < 0.001). Exercise was associated with reduced prevalence of all individual CIPN symptoms (numbness and tingling, pain, interference in daily living). Higher exercise was associated with lower CIPN regardless of chemotherapy regimen. Conclusions: CIPN is persistent several years following chemotherapy cessation in patients with breast cancer but significantly reduced by exercise in a dose-dependent manner.
A genome-wide association study for doxorubicin-induced cardiomyopathy in childhood cancer survivors from the St. Jude lifetime cohort (SJLIFE) and the childhood cancer survivor (CCSS) studies.
Authors: Petrykey Kateryna , Wang Huiqi , Im Cindy , Dixon Stephanie B , Ehrhardt Matthew J. , Mulrooney Daniel A. , Sharafeldin Noha , Wang Xuexia , Jefferies John L. , Oeffinger Kevin C. , Chow Eric Jessen , Gramatges Maria Monica , Bhatia Smita , Robison Leslie L. , Ness Kirsten K. , Hudson Melissa M. , Burridge Paul , Armstrong Gregory T. , Yasui Yutaka , Sapkota Yadav
Published: June 2023

12088

Background: Treatment of childhood cancer using doxorubicin is associated with a well-established dose-related risk of cardiomyopathy, which can lead to heart failure and affects ~7-10% of exposed children and adolescents. Here, we identified a genetic variant associated with risk of doxorubicin-induced cardiomyopathy (diCM) in survivors of childhood cancer. Methods: A genome-wide association study using common variants (MAF≥5%; whole-genome sequencing data) was performed among 993 SJLIFE survivors of European ancestry (median age, 36.6 years; range, 8.7-62.2 years) treated with doxorubicin only (210 with diCM; defined as CTCAE grade ≥2 clinically assessed cardiomyopathy). Replication analyses were performed separately among 1,430 CCSS survivors of European ancestry (median age, 35.4 years; range, 15.8-60.7 years) and 159 SJLIFE survivors of African ancestry (median age, 32.6 years; range, 8.9-61.1 years) exposed to doxorubicin only. Analyses were adjusted for age at primary cancer diagnosis, sex, doxorubicin dose, age at last contact and top five principal components. Results: We identified a genome-wide significant association between a novel locus near HS3ST4 and diCM risk in SJLIFE survivors of European ancestry (rs112474856; OR = 2.78; P= 3.3×10-8). This association replicated in CCSS survivors of European ancestry (OR = 1.74, P= 0.036) but had an opposite effect among SJLIFE survivors of African ancestry (OR = 0.34, P= 0.028). SNP rs112474856 did not show significant association with diCM risk in two independent datasets including survivors of European ancestry in SJLIFE (OR = 1.20; P= 0.71) and CCSS (OR = 1.02; P= 0.98) who were not exposed to doxorubicin but were treated with daunorubicin or chest radiotherapy, suggesting doxorubicin specificity. No association was observed between rs112474856 and risks of cardiomyopathy (OR = 1.00; P= 0.88) or heart failure (OR = 1.00; P= 0.59) in 361,194 UK Biobank participants from the general population. HS3ST4 was significantly upregulated ( P= 4.7×10-6) in response to doxorubicin treatment in human induced pluripotent stem-cell-derived cardiomyocytes from patients with diCM. HS3ST4 encodes heparan sulfate, the latter was recently linked to immune activation, cardiac fibrosis, and heart failure. Conclusions: Leveraging the two largest cohorts of childhood cancer survivors in North America, we identified and replicated a novel locus for diCM which was associated with increased risk in survivors of European ancestry but decreased in their African counterpart.
Long-term prospective data on correlation between overall mortality and HADS (Hospital Anxiety and Depression Scale) assessed psychological distress in prostate cancer patients (11 year follow-up data).
Authors: Sundar Santhanam , Shawcroft Ewan , Jones Lauren , O'Cathail Micheal , Hosni Shaymaa Usama , Little Jessica , Walker Georgina , Cox Ashley , Fergusson Eamonn
Published: June 2023

12091

Background: We prospectively assessed whether Psychological factors such as anxiety and depression can have a detrimental effect on long term overall survival of prostate cancer patients (pts). Methods: Prostate cancer pts participating in an ethics Committee approved, Prospective study evaluating an Andropause rating scale. All pts had radical radiotherapy with androgen deprivation therapy. Pts completed a baseline HADS questionnaire before any treatment was initiated & at 3mths & after completion of hormone therapy. Patient characteristics: Median age: 69 yrs (50 to 78 yrs). Charlson Comorbidity Index (CCI) prevalence at baseline as follows CCI-I 6.1%; CCI-II: 33.8%; CCI-III: 37.2%; CCI-IV: 14.2%; CCI-V: 6.1% and CCI-VI: 2.7%.; At the survival update in Feb 2023, 49.3% of patients have died [n = 148]; Gleeson grade was Low risk in 7.2%; Intermediate in 53.4% and high risk in 39.2%; Baseline PSA was < 10 ug/L in 45.3%; 10-20 ug/L in 33.1% and > 20 ug/L in 21.6% ; Tumour stage was T1 in 8.1% ; T2 in 63.5% and T3 in 28.4%. Baseline Median serum testosterone was 11.9 nmol/l (min 2.6 and max 26.7). Hormone duration was < 3 mths in 22.3%; 3-6mths in 35.8% ; 6 to < 36mths in 19.6% and > 36mths in 22.3%. Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) of overall mortality, while controlling for the following covariates (Age, T stage, Gleeson risk category, PSA Category, Baseline Serum Testosterone, ADT duration category and Charlson Comorbidity index). Results: Higher anxiety at time of diagnosis had a statistically significant adverse effect on overall survival (table); Higher depression symptoms at baseline did not affect survival but depressive symptoms after completing cancer treatment did affect all-cause mortality in this mature dataset with a median follow up of more than 11 years. Conclusions: Higher anxiety and depression symptoms in prostate cancer patients are associated with significantly higher long-term all-cause mortality. [Table: see text]