bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk stratification tools to help decide on adjuvant chemotherapy usage in resected soft tissue sarcomas: A 10 year review of an Irish sarcoma centre experience.
Authors: Weadick Catherine , Keogh Rachel J , Goggin Caitriona , Murphy Jake , Feeley Linda , Bennett Michael William , O'Reilly Seamus , Redmond Henry Paul , Kelly Jason , O'Mahony Deirdre , Noonan Sinead , Clover Jim , Bambury Richard Martin 
Published: June 2023

11575 Background: Soft tissue sarcoma (STS) is comprised of 80 pathologic subtypes based on a combination of distinctive morphological, immunohistochemical and molecular features. Adult-type soft tissue and visceral sarcomas are rare, with an estimated incidence of 4-5/100,000/year in Europe. The National Comprehensive Cancer Network (NCCN) guidelines recommend consideration of neo-adjuvant or adjuvant systemic treatment in resectable stage III (high grade tumours which are >5cm) and also in those who need to undergo an amputation or radical resection with adverse functional outcomes. The Sarculator risk prediction tool has identified a threshold of risk above which the administration of chemotherapy may provide an overall survival benefit. This can be applied to the most common histologic subtypes. Patients affected by these subtypes and with a 10-year predicted OS likelihood <60% are considered as high risk and therefore, should be considered for adjuvant chemotherapy. Alternatively, tumours considered at high risk of recurrence based on size >5cm and high grade histology, may benefit from adjuvant chemotherapy. Therefore, the aim of this project is to review the outcomes of resected extremity/trunk soft tissue sarcoma and assess the prognostic accuracy of these risk prediction methods. Methods: All new patients with resected STS discussed in the STS MDT in Cork University Hospital between Jan 2012 – Dec 2021 were identified. The histology and imaging of the identified patients were reviewed. Data regarding demographics, histology, treatment and outcomes was collected. Risk assessment using AJCC and Sarculator score was done on all patients with an extremity or trunk sarcoma. Overall survival was recorded and assessed including Kaplan Meier method for time to event analysis. Results: 200 patients were identified as having an STS resected - 134 of these were located on the trunk or extremities representing 24 different histological subtypes. Sarculator score was calculated for 60 of these (well differentiated liposarcomas, desmoid tumours, and dermatofibrosarcoma protuberans were excluded). 3 patients received adjuvant chemotherapy and 4 patient neoadjuvant chemotherapy. Overall survival data is presented below. Conclusions: Our cohort is representative of the broad histological subtypes expected in sarcoma. Sarculator score results correlate with international outcomes, with higher scores associated with increased mortality. In our cohort, sarculator score was more predictive of outcome than tumour grade/size alone. [Table: see text]
DCK expression by RNAseq as a potential biomarker of gemcitabine response in sarcoma.
Authors: Liebner David A. , Fetzer Erin A , Husain Marium , Chen James Lin , Tinoco Gabriel 
Published: June 2023

11578 Background: Deoxycytidine kinase (DCK) is responsible for activation of gemcitabine by phosphorylation of gemcitabine to its monophosphate form. Studies have suggested that DCK expression may be correlated to response to gemcitabine in various solid tumors, and that downregulation of DCK may be at least partly responsible for gemcitabine-resistance in vitro. However, the significance of DCK expression in sarcomas as a biomarker of response to gemcitabine remains poorly characterized. Methods: Participants enrolled in the prospective Electronic Health Record (EHR)-Based Comprehensive Bone and Soft Tumor Registry ( NCT02677961 ) at The Ohio State James Cancer Center who had received gemcitabine-based chemotherapy for the treatment of bone and soft tissue sarcoma were eligible for this study. A total of 179 patients were identified who had received at least one cycle of gemcitabine-based chemotherapy, between January 1st, 2014, to December 31st, 2022. Whole exome RNASeq expression data was available for 36 of these patients who had received gemcitabine-based chemotherapy in the setting of active disease. Results: Of the 36 patients included in this study, 22 were female and 14 were male. Nine different main disease types were identified in the patient subset. These include angiosarcoma (8), chondrosarcoma (1), leiomyosarcoma (16), liposarcoma (3), malignant peripheral nerve sheath tumor (1), myxofibrosarcoma (2), osteosarcoma (2), undifferentiated pleomorphic sarcoma (3), and undifferentiated spindle cell sarcoma (1). The median time to treatment discontinuation (TTD) among all patients was 178 days. Among DCK low-expressors (n = 16), the median TTD was 86 days; among high-expressors (n = 16), the median TTD was not reached. Differences between groups did not reach statistical significance (HR = 0.55, p = 0.14). Conclusions: DCK expression by clinical RNASeq is a potential biomarker of gemcitabine-response in sarcoma, but larger studies are necessary to evaluate the potential clinical significance and possible role of DCK expression in identifying patients most likely to benefit from gemcitabine-based chemotherapy.
Effect of a telephone-based weight loss intervention (WLI) on weight at 12-months in women with early breast cancer: Results from the Breast Cancer Weight Loss (BWEL) trial.
Authors: Ligibel Jennifer A. , Ballman Karla V. , McCall Linda Mackie , Goodwin Pamela Jean , Weiss Anna , Delahanty Linda , Alfano Catherine M. , Crane Tracy E , Neuhouser Marian L. , Spears Patricia , Hershman Dawn L. , Paskett Electra D. , Hopkins Judith O. , Bernstein Vanessa , Stearns Vered , White Julia R. , Wadden Thomas , Winer Eric P. , Partridge Ann H. , Carey Lisa A. 
Published: June 2023

12001 Background: Obesity is a poor prognostic factor in early breast cancer. The Breast Cancer Weight Loss (BWEL) trial (Alliance for Clinical Trials in Oncology A011401; NCT02750826) evaluates the impact of a WLI on invasive disease-free survival in breast cancer patients (pts) with a body mass index (BMI) ³27 kg/m2. Here we report the impact of the WLI on weight change. Methods: Eligible pts were within 14 months of diagnosis of stage 2-3 HER2-negative breast cancer, had completed chemotherapy and radiation (if administered), and were randomized 1:1 to a telephone-based WLI plus health education (HE) or an HE alone control group. The WLI was delivered by telephone-based health coaching and focused on caloric restriction and increased exercise. Height and weight were measured at baseline and 12 months. Changes in weight were compared between groups. Analysis was performed with univariable and multivariable (including arm, baseline weight, menopausal status, race/ethnicity, and hormone receptor [HR] status) regression models. A 0.05 level of significance was used. Results: 3181 women were randomized between 8/2016 and 2/2021. At baseline, mean BMI was 34.5 (±5.74) kg/m2, mean age was 53.4 (±10.58) years, and 57% of pts were postmenopausal at the time of diagnosis. 80.3% of participants were White, 12.8% were Black, and 7.3% were Hispanic. Follow-up weight was available from 2293 pts alive and disease-free at 12 months. The WLI led to a significant decrease in weight relative to controls; pts randomized to WLI lost an average of 4.8% (±7.9) of baseline body weight at 12 months vs. 0.8% (± 6.4) weight gain in controls (p<0.0001). Pts randomized to WLI experienced significant weight loss (vs controls) across demographic and tumor factors (Table). WLI effect differed significantly by menopausal status (interaction p value = 0.0057) and race/ethnicity (interaction p-value = 0.019), but not HR status (interaction p-value = 0.17). Conclusions: A telephone-based WLI induced significant, clinically meaningful weight loss in breast cancer pts with overweight and obesity across demographic and tumor factors. Additional tailoring of the WLI could be useful to enhance weight loss in Black and younger pts. Further follow-up of the BWEL trial will evaluate whether the WLI improves disease outcomes. Support: U10CA180821, U10CA180882, UG1CA189823; https://acknowledgments.alliancefound.org . Clinical trial information: NCT02750826 . [Table: see text]
Chemotherapy induced peripheral neuropathy (CIPN) due to paclitaxel versus docetaxel in patients with early-stage breast cancer receiving taxane therapy: SWOG S1714.
Authors: Trivedi Meghna S. , Unger Joseph M. , Hershman Dawn L. , Darke Amy , Hertz Daniel Louis , Brannagan Thomas , Smith Stephanie , Schneider Bryan P. , Irvin William Johnson , Hathaway Amanda Redden , Vander Woude Amy C. , Gudena Vinay K. , Henry Norah Lynn , Fisch Michael Jordan 
Published: June 2023

12003 Background: Paclitaxel (Pac) and docetaxel (Doc) are used to treat early-stage breast cancer (BC). CIPN due to taxane therapy can cause sensory and motor deficits. CIPN symptoms caused by Pac versus Doc are not well described. Methods: SWOG S1714 enrolled patients ≥ 18 years with Stage I-III primary NSCLC, BC, or ovarian cancer starting treatment with a taxane-based regimen. CIPN was assessed by the patient-reported EORTC QLQ-CIPN20 (CIPN-20) and clinician-assessed NCI-CTCAE. Assessments occurred at baseline and 4, 8, 12, and 24 weeks after registration. Increase in CIPN-20 sensory subscale score ≥ 8 points was considered clinically meaningful. Chi-square and Fisher tests were used for baseline comparisons; logistic regression was used for multivariable analyses. Results: Among 1336 enrolled patients, 1106 of eligible patients had a diagnosis of BC, with median age 54.8 y (range 23.9-84.2 y), 99.3% female, and 72.3% White/11.3% Black/4.6% Asian/11.1% Hispanic/Latino. Pac was administered to 615 (55.6%) and Doc to 491(44.3%) patients. Between the Pac and Doc cohorts, there were significant baseline differences in median age, diabetes, and performance status. At 24 weeks, the proportion of patients with ≥8 point increase in CIPN-20 sensory score was lower for Doc (40.5%) vs Pac (50.2%) (odds ratio [OR] 0.64, 95% CI 0.50, 0.82; multivariable adjusted p<.001). At nearly every timepoint through 24 weeks, patients treated with Pac had more sensory and motor neuropathy as measured by both the CIPN-20 and NCI-CTCAE (Table). Conclusions: In this diverse cohort of patients with BC, the frequency of CIPN was higher than expected for both Pac and Doc and more severe in patients receiving Pac. These findings based on CIPN-20 can assist in treatment decision-making about taxane therapy. Long term follow up will better characterize the differences in the trajectory of CIPN between Pac and Doc. Funding: NIH/NCI/NCORP grant UG1CA189974. Clinical trial information: NCT03939481. [Table: see text]
Randomized double-blind, placebo-controlled study of topical diclofenac in prevention of hand-foot syndrome in patients receiving capecitabine.
Authors: Santhosh AKHIL , Batra Atul , kumar akash , Pramanik Raja , Gogia Ajay , Cheung Winson Y. , Sharma Atul , Prasad Chandra Prakash , Sehgal Tushar 
Published: June 2023

12005 Background: Capecitabine induced HFS is associated with deterioration of quality of life of patients and dose of capecitabine is often reduced to manage this adverse event. Celecoxib is the only effective intervention in preventing HFS; however, its widespread use is limited due to its own safety concerns. We conducted this study to assess the efficacy of topical diclofenac in preventing capecitabine induced HFS. Methods: Patients with breast and gastrointestinal (GI) cancers, planned for capecitabine (monotherapy or combination) treatment were randomized in 1:1 to receive topical diclofenac or placebo gel for 4 cycles or until development of HFS, whichever was earlier. Stratified (male or female; capecitabine monotherapy or combination therapy) permuted variable size block randomization was done using a computer-generated random numbers sequence. Primary objective was to compare the incidence of grade 2 or higher HFS in diclofenac and placebo arms. Secondary objectives were incidence of any grade HFS, capecitabine dose changes due to HFS and self-reported adherence with application. Results: A total of 263 patients were randomized to apply topical diclofenac gel (n=130) or placebo (n=133). Baseline characteristics were similar in both the arms (Table). The incidence of grade 2 or higher HFS was 3.8% (95% CI, 1.6%-8.9%) in the diclofenac arm compared with 15.0% (95% CI, 9.9%-22.2%) in the placebo arm (P=0.003). Any grade HFS was significantly lower in the study arm compared with the placebo arm (6.1% vs 18.1%; P=0.003). A lower incidence of HFS was observed in the diclofenac arm across the subgroups (breast and GI cancers; males and females). Capecitabine dose reductions were less frequent in the diclofenac arm (3.8%) compared with the placebo arm (15%) (P=0.002). Adherence to topical treatment was similar in the diclofenac arm (96.7 +/- 19.1%) compared with the placebo arm (94.0 +/- 28.3%) (P=0.36). Other capecitabine associated adverse events, including diarrhea, mucositis, and myelosuppression were not significantly different in both the arms. Conclusions: Topical diclofenac is effective in preventing all grades of HFS in patients receiving capecitabine. Diclofenac application was also associated with lesser dose reductions of capecitabine. This trial establishes topical diclofenac as the new standard of care to prevent capecitabine associated HFS. Clinical trial information: CTRI/2021/01/030592 . [Table: see text]
Telehealth-based psychological intervention for caregivers of patients with primary malignant brain tumors: A randomized controlled trial.
Authors: Forst Deborah Anne , Podgurski Alyx F. , Strander Sumita Madhok , Datta Shibani , Pintro Kedie , Horick Nora K. , Sannes Timothy S. , Greer Joseph A. , El-Jawahri Areej , Jacobs Jamie M. , Temel Jennifer S. 
Published: June 2023

12008 Background: Caregivers of patients with primary malignant brain tumors (PMBT) face unique challenges caring for someone with a progressive neurological illness. In preliminary studies, we found that 50% or more of caregivers had clinically significant anxiety symptoms in the months following the patient’s PMBT diagnosis. However, few interventions have been developed to specifically target anxiety symptoms in this population. Methods: We conducted a randomized controlled trial evaluating the efficacy of NeuroCARE, a population-specific intervention addressing anxiety in caregivers of patients receiving treatment at two academic centers. Eligible caregivers were within six months of the patient’s PMBT diagnosis and had clinically significant anxiety symptoms (score ≥ 5 on the Generalized Anxiety Disorder-7 tool). Participants were randomized 1:1 to NeuroCARE or usual care. NeuroCARE consisted of six one-on-one telehealth sessions with a mental health clinician or trainee and incorporated evidence-based skills for 1) coping with worry, 2) using assertive communication techniques, 3) optimizing social support, and 4) promoting relaxation and healthy sleep. Participants completed questionnaires at baseline, 11 weeks (immediately post-intervention) and 16 weeks (1 month post-intervention). Our primary endpoint was anxiety symptoms at 11 weeks (Hospital Anxiety and Depression Scale (HADS) – Anxiety Subscale score). We also assessed depression symptoms (HADS – Depression Subscale), quality of life (QOL; Caregiver QOL survey), caregiver burden (Caregiver Reaction Assessment), self-efficacy (Lewis Cancer Self-Efficacy scale), coping (Measure of Current Status) and post-traumatic stress disorder (PTSD) symptoms (PTSD Checklist for DSM-5). We used analysis of covariance to evaluate the effect of NeuroCARE versus usual care on these outcomes. Results: We enrolled 120 caregivers (60 per arm, mean age = 53 years, 83% female), the majority of whom were caring for their spouse/long-term partner (70%), child (17%), or parent (7%). At 11 weeks, NeuroCARE participants reported significantly lower anxiety symptoms than those assigned to usual care (means: 8.87 vs 10.69, p = 0.008). NeuroCARE caregivers also reported significantly lower depression symptoms (6.08 vs 7.77, p = 0.004) and better self-efficacy (128.81 vs 111.17, p < 0.001) and coping (32.25 vs 25.65, p < 0.001) at 11 weeks. Study groups did not differ with respect to caregiver burden, PTSD symptoms, or QOL at 11 weeks. Conclusions: A population-specific telehealth-based psychological intervention (NeuroCARE) led to significantly lower anxiety and depression symptoms and better self-efficacy and coping among caregivers of patients with PMBT compared with usual supportive care. Clinical trial information: NCT04109209 .
Cost-utility of geriatric assessment in older adults with cancer: Results from the 5C trial.
Authors: Sahakyan Yeva , Li Qixuan , Abrahamyan Lusine , Puts Martine , Brennenstuhl Sarah , Anwar Mohammed Rashidul , Yeretzian Shant , Matosyan Emma , Mclean Bianca , Strohschein Fay , Wills Aria , Tomlinson George , Alibhai Shabbir M.H. 
Published: June 2023

12012 Background: Geriatric assessment is a guideline-recommended approach to optimize cancer management in older adults. We conducted a cost-utility analysis alongside the recently published 5C randomized controlled trial to compare geriatric assessment and management (GAM) with usual care in older adults with cancer. Methods: The economic evaluation was conducted from a societal perspective, using a 12-month time horizon. The 5C study enrolled patients age 65+ from 8 Canadian hospitals and randomly assigned them to receive GAM or usual care. Patients were initiating systemic therapy with curative or palliative intent. Quality-adjusted life years (QALYs) were measured using the EQ-5D-5L questionnaire. Healthcare utilization was evaluated using cost diaries and chart reviews. The primary outcome, an incremental monetary benefit (INMB), was evaluated for the full sample and for preselected subgroups. Multiple imputation was used to account for missing data. The 95% confidence intervals (CI) were computed using bootstrapping. Results: The study included 350 patients, of which 173 received GAM and 177 received usual care. At 12 months, the average QALYs per patient were 0.747 and 0.753 for GAM and usual care respectively (ΔQALY = -0.006, 95%CI: -0.06 to 0.05). The total average costs per patient were $48,397 and $45,342 for GAM and usual care (ΔCost = $3,078 (95% CI: -$5,336 to $12,050). At a cost-effectiveness threshold of $50,000/QALY the INMB was negative (-$3,962; 95% CI: -$7,117 to -$794) meaning that GAM was not cost-effective compared to usual care. In a subgroup analysis the INMB was positive ($4,639, 95% CI: $61 to $8,607) for patients treated with curative intent, and the intervention was cost effective in 78% of simulations, but remained negative (i.e. not cost-effective) for patients treated with palliative intent (INMB -$13,307, 95% CI -$18,063 to -$8,264). Conclusions: This is the first cost-utility analysis of GAM in cancer. The findings showed that GAM was cost-effective for cancer patients treated with curative intent but not for patients with palliative intent. Although the primary results of the 5C trial were negative, extrapolating our costing data to positive GAM trials like GAIN, GAP70, and INTEGERATE will provide a more complete picture of the cost effectiveness of GAM in this setting. Clinical trial information: NCT03154671 .
Impact of immune checkpoint inhibition on ovarian reserve in patients with melanoma enrolled in the ECOG-ACRIN E1609 adjuvant trial.
Authors: Buchbinder Elizabeth Iannotti , Song Zihe , Lee Sandra J. , Keefe Kimberly W. , Manos Michael P. , Tarhini Ahmad A. , Dougan Michael L. , Cohen Justine Vanessa 
Published: June 2023

12013 Background: Immunotherapy with immune checkpoint inhibition (ICI) is being widely adopted in the treatment of patients with a wide range of malignancies. However, we have no data on how these therapies influence fertility or ability to undergo fertility treatments after therapy. Within the melanoma community numerous women of childbearing age have been treated with ICI including ipilimumab, nivolumab and pembrolizumab. Anti-mullerian hormone (AMH) is a biomarker of ovarian reserve and a predictor of response to fertility treatments, including in vitro fertilization (IVF). In women under the age of 35 who have no reproductive pathology, AMH should be detectable and remain relatively stable over time. Above the age of 35 AMH decline accelerates as the number of eggs decreases more rapidly due to normal ovarian aging. Methods: Pre and post-treatment samples from women aged 20-35 whose melanoma was treated with 3 mg/kg ipilimumab (57%) or 10 mg/kg ipilimumab (43%) in the adjuvant setting on trial ECOG-ACRIN E1609 were analyzed in collaboration with the BWH Reproductive Endocrine Laboratory. Serum samples were tested for luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, AMH and prolactin. Results: Samples from E1609 were available from 28 female patients with a median age of 28 (min 20, max 35). The median time between samples was 8.0 months (min 0.7, max 16.4). 53% of patients had stage IIIB melanoma, 43% stage IIIC and one patient had M1a disease. AMH, estradiol and LH significantly decreased after treatment (p < 0.001, p = 0.016, p = 0.012, respectively) (Figure 1); there was no significant difference in the level of FSH and prolactin before and after the treatment (p = 0.68, p = 0.12, respectively). The median AMH was 4.24 ng/mL in the pre-treatment group and 3.51 in the post-treatment group. Conclusions: In this study of young women treated with ipilimumab there was a significant decrease in AMH before and after ICI therapy suggesting that ovarian reserve and possibly female fertility may be impacted by immune checkpoint inhibition. Further investigation is needed to look at PD-1 inhibition and combination immunotherapy effects on ovarian reserve and female fertility. In addition, there is a similar need to examine ICI effects on male fertility.