bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant chemotherapy in high-risk soft tissue sarcomas: Results of the expanded cohort of myxoid liposarcoma of the randomized clinical trial from the Italian Sarcoma Group (ISG), the Spanish Sarcoma Group (GEIS), the French Sarcoma Group (FSG), and the Polish Sarcoma Group (PSG).
Authors: Gronchi Alessandro , Palmerini Emanuela , Quagliuolo Vittorio , Martin Broto Javier , Lopez-Pousa Antonio , Grignani Giovanni , Brunello Antonella , Blay Jean-Yves , Diaz Beveridge Robert , Ferraresi Virginia , Lugowska Iwona , Pizzamiglio Sara , Verderio Paolo , Fontana Valeria , Donati Davide Maria , Palassini Elena , Stacchiotti Silvia , Miceli Rosalba , Dei Tos Angelo Paolo , Casali Paolo Giovanni 
Published: June 2022

11508 Background: An ISG, GEIS, FSG and PSG randomized trial on 3 cycles of neoadjuvant epirubicine+ifosfamide (EI) versus a histology-tailored (HT) regimen in selected localized high-risk STS showed some superiority of EI in all histologies with the exception of Myxoid Liposarcoma (MLPS) where EI and HT regimens seemed equivalent (J Clin Oncol 2020; 38:2178-86). This MLPS cohort was expanded with the aim to assess the non-inferiority of the HT regimen compared to EI. Methods: This was a multicenter European randomized trial comparing EI versus a HT regimen. Patients (pts) had localized high-risk (grade = 3; size >5 cm; deeply seated) undifferentiated pleomorphic sarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, synovial sarcoma or MLPS of extremities or trunk wall. Primary end-point was Disease Free Survival (DFS). Secondary end-point was Overall Survival (OS). The MLPS cohort was expanded after the results of the 3rd interim analysis (Lancet Oncol 2017; 18:812-22) in order to reject the hypothesis that HT regimen trabectedin is associated with a HR of relapse = 1.25 with a non-inferiority design. To this aim, a Bayesian monitoring approach was used until the probability that the true HR is higher than 1.25 was greater than 80% or smaller than 5%. Results: From May 2011 to June 2020, 101 pts affected by high-risk MLPS were randomized, 56 to EI and 45 to HT regimen. The median follow-up was 66 months (IQ range 37-89). Median size was 107 mm (IQ range 84-143), 108 mm (IQ range 86-150) in the EI and 106 mm (IQ range75-135) in the HT arm. The DFS and OS probabilities at 60 months were 0.86 and 0.73 (HR:0.60; 95%CI: 0.24-1.46; log rank p = 0.26 for DFS) and 0.88 and 0.90 (HR:1.20; 95%CI:0.37-3.93; log rank p = 0.77 for OS), in the HT and EI arm, respectively. 5-yr observed and Sarculator-predicted OS were 0.89 (95% CI 0.82-0.97) and 0.80 in all patients (p = 0.020), 0.90 (95% CI 0.81-1.00) and 0.79 in the EI arm (p = 0.049) and 0.88 (95% CI 0.77-1.00) and 0.81 in the HT arm (p = 0.204) respectively. Conclusions: In the expanded cohort of MLPS, the HT neoadjuvant therapy trabectedin was not inferior to EI. While survival in both arms was better than predicted by Sarculator, it is left to understand whether this patient population, who had on average a lower Sarculator-predicted risk of death compared with the rest of the trial population, may benefit from a neoadjuvant therapy. Clinical trial information: NCT01710176.
Platelet derived growth factor receptor alpha (PDGFRA) mutant gastrointestinal stromal tumours (GISTs): Clinicopathological characteristics and outcomes from a regional centre in the United Kingdom.
Authors: Favara David M , Wong Han Hsi , Harrington Jennifer , Giger Olivier , Bulusu Venkata Ramesh 
Published: June 2022

11534 Background: GISTs are the most common mesenchymal tumours of the gastrointestinal tract with an annual incidence of 10-15 per million. 10% of GISTS have activating mutations in the PDGFRA gene. We report our 13 year experience of all the PDGFRA-mutated GISTs in our regional centre in Cambridge. Methods: PDGFRA-mutant GISTs were identified from the Cambridge GIST database. Demographics, clinical and histopathological features, survival and response to tyrosine kinase inhibitors of all the patients from 2008-2021 were reviewed. Results: n = 50 (male:female 1.5:1) Median age 68 years (range 19-87). 8% of patients were under the age of 40 years. Tumour size ranged from 1-26 cm with a median of 5 cm. Mitotic index ranged from 1-51 with a median of 1 mitosis/5mm2. 52% of GISTs were located in the gastric body. Histological subtypes: 44% epithelioid, 36% mixed and 20% spindle cell. 38% of cases had high KIT expression (immunohistochemistry), whilst 48% had patchy expression and 14% were negative. Most were DOG1-positive (94%). 76% had radical surgery, 60% had laparoscopic resection. 24% were assessed as being high risk GISTs using the modified AFIP model contrasted to 13% being high risk with prognostic contour mapping. 13% developed metastatic disease with liver being the most common metastatic site. The table shows PDGFRA mutational analysis results: 58% had a D842V mutation. None had a KIT mutation. With a median follow up of 55.1 months, 82% were alive. 6 patients died from metastatic GIST and 3 from other causes. Median time to metastatic disease in resected GISTs was 30.1 months and median time from metastatic diagnosis to death was 18.5 months. Patients who presented with metastatic disease had poor survival compared with patients with localised disease ( p=0.001). 8 patients were treated with tyrosine kinase inhibitors including imatinib, sunitinib and regorafenib prior to 2020 with no objective responses. 3 patients were treated with Avapritinib since 2020 within the compassionate use programme. All 3 patients had partial responses and 2 patients are continuing Avapritinib with no grade 3 adverse events. Conclusions: We report the largest single centre PDGFRA-mutant GIST cohort from Europe. Male preponderance and exclusive gastric location were observed. KIT expression was patchy to negative in the majority of patients. 58% had PDGFRA D842V mutations for which Avapritinib has been recently approved. No objective responses were seen with imatinib, sunitinib or regorafenib. Our early experience with Avapritinib is promising.[Table: see text]
Clinical markers of immunotherapy outcomes in sarcoma.
Authors: Husain Marium , Liebner David A. , Kim Hangil , Xu Menglin , Chen James Lin , Tinoco Gabriel 
Published: June 2022

11578 Background: Despite immunotherapy’s promise in oncology, its use for sarcoma remains challenging. There are no sarcoma-specific biomarkers for immune checkpoint inhibitors (ICI). Previously, we reported our institutional experience highlighting ICI activity in 29 patients with sarcoma. In this updated study, we further explore responses to ICI based on ICI regimen and other covariates to identify significant clinical factors in sarcoma outcomes. Methods: Patients in the Ohio State University Sarcoma clinics were enrolled in the Sarcoma Retrospective ICI database from January 1, 2015 through November 1, 2021. Data included treatment regimen (single agent ICI or ICI+combination) along with covariates: stage, age, gender, histology, change in neutrophil-to-lymphocyte ratio (NLR), number of cycles of ICI and immune-related adverse events (irAE). ICI+combination was further categorized into ICI+chemotherapy, ICI+radiation, ICI+surgery or ICI+multiple (more than 2 modalities). Statistical analysis included log rank tests and proportional hazard regression. The primary objective was to evaluate overall survival (OS) and progression-free survival (PFS). Results: One hundred and thirty-five patients met inclusion criteria. We demonstrated improved OS in patients treated with ICI+combination (p = 0.014, median 64 weeks), but no effect on PFS (p = 0.471, median 31 weeks). Whether patients had received single agent or combination ICI, those who received more than 3 cycles of ICI had an improved OS and PFS (p < 0.05 for both). Patients who received single-agent ICI and whose change in NLR was less than 5 had an improved OS (p = 0.002); this was not seen in patients who received ICI+combination therapy (p = 0.441). Patients who had a documented irAE of dermatitis had improved OS but only in the ICI+combination cohort (p = 0.021). There were no differences in OS based on age, gender, histology or sub-categories of ICI+combination. This was not the case for PFS; patients who received any ICI regimen and were younger than 70 had a worse PFS (p = 0.036). Patients who developed an irAE, specifically colitis (p = 0.009), hepatitis (p = 0.048) and dermatitis (p = 0.003) had an improved PFS. There were no differences in PFS based on ICI regimen (or sub-categories of ICI+combination), gender, histology, change in NLR or grade of irAE. Our ICI cohort results are consistent with historical data from our previous study. Further, irAEs are similar to historical data. Conclusions: This retrospective study demonstrates that ICI+combination therapy can improve OS in sarcoma. This is consistent with our prior results of ICI in sarcoma. Benefits in OS/PFS were seen in patients who received more than 3 cycles of ICI and developed certain irAE. These results can direct the optimal duration of ICI therapy. Those with decreased change in NLR also had improved OS, demonstrating a potential prognostic biomarker. Further studies are needed to validate our findings.
Rural-urban disparities in Geriatric Assessment (GA) impairments and mortality among older adults with cancer: Results from the Cancer and Aging Resilience Evaluation (CARE) Registry.
Authors: Fowler Mackenzie , Kenzik Kelly , Al-Obaidi Mustafa , Harmon Christian , Giri Smith , Arora Sankalp , Khushman Moh'd M. , Outlaw Darryl Alan , Bhatia Smita , Williams Grant Richard 
Published: June 2022

12012 Background: Rural-urban disparities persist in cancer incidence and mortality, despite improvement in cancer screening and treatment. Older adults are at increased risk for cancer, represent the majority of cancer cases, and are more likely to reside in rural areas than younger adults are. GAs are recommended in clinical management of older adults with cancer, in part to identify aging-related impairments predictive of adverse outcomes; few studies have explored rural-urban disparities in GA impairments and mortality among older patients with cancer. Methods: We included 937 older adults (≥60y) from the CARE registry recently diagnosed with cancer who underwent GA at their first pre-chemotherapy visit to the UAB oncology clinic. Rural-urban status using Rural-Urban Commuting Area (RUCA) codes, classified the cohort by residence in metropolitan, micropolitan, and rural/small town areas. We included self-rated performance status (PS) (≥2 on Eastern Cooperative Oncology Group PS), instrumental activities of daily living (IADL) [≥1 impairment], physical and mental health-related quality of life (HRQoL) [t-score < 40 on PROMIS 10-item Global Health], and overall survival as outcomes. Logistic regression evaluated the association between rural-urban status and each outcome (except overall survival, where we used Cox regression analyses). Micropolitan residence was chosen as the reference category due to similar high risk in both rural and urban areas. Results: Median age at study participation was 69.0y (Interquartile range: 64.0-74.0); 12.4% resided in rural, 14.8% in micropolitan and 72.8% in urban areas; 22.5% were diagnosed with colorectal cancer, 19.0% with pancreatic, and 12.4% with hepatobiliary; 74.7% were Stage III/IV. Participants in rural areas were more likely to be white and less educated. After adjustment for age, sex, race, education and cancer type/stage, rural residence was associated with increased odds of impaired PS (OR = 1.93, 95% CI: 1.10-3.40), limitations in IADLs (OR = 1.79, 95% CI: 1.03-3.10), and impaired physical HRQoL (OR = 1.84, 95% CI: 1.05-3.22) compared to micropolitan residence. Urban residence was not significantly associated with any GA outcomes compared to micropolitan residence. Rural residence was associated with higher hazard of death compared to micropolitan residence (HR = 1.88, 95% CI: 1.09-3.24) as well as urban residence (HR = 1.67, 95% CI: 1.13-2.45). Conclusions: Among older adults with newly diagnosed cancer, rural residence was associated with impaired PS, limitations in IADLs, impaired physical HRQoL, and reduced overall survival. Implementation of routine GA among older adults in rural areas may aid in early identification and intervention on GA impairments to improve cancer outcomes.
New strategies for multimodal analgesia in patients with high-risk geriatric cancer in perioperative period.
Authors: Tumanyan Sergey V. , Rozenko Dmitry A. , Oros Oksana V. , Shepelenko Aleksandr V. , Chekmezova Svetlana A. , Popova Natalia N. 
Published: June 2022

12046 Background: Perioperative pain (POP) in high-risk geriatric patients with cancer (HRGCP) is an important issue. The purpose of this study was to optimize perioperative analgesia in HRGCP. Methods: This randomized study of the quality and effectiveness of perioperative analgesics included 115 HRGCP aged 64-88 years who underwent surgeries on the organs of the chest, abdomen and pelvis for various cancers. The patients were divided into 2 groups. Group 1 (n = 52): patient-controlled analgesia with morphine and nonsteroidal anti-inflammatory drugs (NSAIDs); group 2 (n = 63): ultrasound-guided bilateral transversus abdominis plane (TAP) block with ropivacaine. Intraoperative and perioperative analgesia was maintained with a continuous infusion of lidocaine, magnesium sulphate, microdoses of fentanyl and NSAIDs. Results and pain syndrome were assessed by monitoring the Efficacy Safety Score (ESS), personal and reactive anxiety, stress response (cortisol, insulin, lactate, glucose), rates of functional activity recovery, the need for opioid analgesics, frequency of postoperative nausea and vomiting (PONV). Results: Patients in group 2 showed a significant decrease in the perioperative need for opioid analgesics and significantly decreased POP. Analysis of variance of mean values revealed statistically lower scores of ESS, visual analogue scale and POP (p < 0.05) during the first 24 hours of perioperative period in group 2 compared with group 1. Patient-controlled analgesia showed analgesic effect in 88.5% (p < 0.05) cases. However, the effect was less pronounced, compared to multimodal analgesia, and did not reduce cognitive disorders. In group 2, opioid-sparing analgesic effect was 95.3% (p < 0.05). Multimodal analgesia reduced the stress response (p < 0.05) in perioperative period and did not cause cognitive dysfunction while reducing PONV episodes, unlike morphine. Despite the minimal doses of narcotic analgesics in group 2, multimodal analgesia provided safe analgesia and functional activity recovery in perioperative period with minimum negative effects of opioids. Conclusions: The strategy of multimodal analgesia based on a combination of intraoperative TAP block and infusions of lidocaine and microdoses of fentanyl can significantly improve the quality of analgesia in perioperative period.
Association of polypharmacy and potential drug-drug interactions with adverse outcomes in older adults with advanced cancer receiving systemic treatment.
Authors: Mohamed Mostafa Refaat , Mohile Supriya Gupta , Juba Katherine , Awad Hala , Wells Megan , Loh Kah Poh , Flannery Marie Anne , Culakova Eva , Tylock Rachael , Desai Nisarg , Bradley Thomas Paul , Onitilo Adedayo A. , Ramsdale Erika E. 
Published: June 2022

12053 Background: Polypharmacy (PP) is common in older adults starting cancer treatment and associated with increased risk of potential drug-drug interactions (PDI). PP and PDI may affect treatment-related outcomes in older patients. This study evaluates the association of PP and PDI with systemic treatment adverse outcomes in older adults with advanced cancer. Methods: This secondary analysis of prospectively collected data from the GAP 70+ Trial (NCT02054741; PI: Mohile) enrolled patients aged 70+ with advanced (i.e. incurable) cancer; had ≥1 geriatric assessment domain impairment; and planned to start a new chemotherapy regimen or another regimen with high risk of toxicity. PP was assessed prior to initiation of treatment and defined as concurrent use of ≥8 medications (meds). PDI among all drugs were reviewed prior to initiation of treatment using Lexi-Interact® Online with category D and X considered “major PDI”. Study outcomes were assessed within 3 months of treatment initiation and included: 1) total number of Grade ≥2 toxicities according to National Cancer Institute Common Toxicity Criteria; 2) total number of Grade ≥3 toxicities; and 3) early treatment discontinuation due to toxicity. Multivariable linear and logistic regression models were used to examine the association of PP and PDI with treatment adverse-outcomes adjusted for age, gender, cancer type, comorbidity, physical function, social support, and study arm. Results: Among 718 participants, the mean age was 77 (range 70-96); 43% were females; and 57% had lung or gastrointestinal cancers. The median number of meds was 5 (range 0-24); 28% received ≥8 concurrent meds; and 25% had ≥1 major PDI. The mean number of Grade ≥2 toxicities for patients with PP was 9.8 versus 7.7 in patients without PP (adjusted β=1.87, standard error [SE]=0.71, P<0.01). The mean number of Grade ≥3 toxicities for patients with PP was 2.9 versus 2.2 in patients without PP (adjusted β=0.59, SE=0.29, P=0.04). Patients with ≥1 major PDI had 59% higher odds of early treatment discontinuation versus those without major PDI (adjusted odds ratio 1.59, 95% confidence interval=1.03-2.46, P=0.03). There was no significant association between PP and early treatment discontinuation. Major PDI were not significantly associated with toxicity (Ps>0.05). Conclusions: In a cohort of vulnerable older adults with advanced cancer, PP and PDI are associated with increased risk of systemic treatment adverse outcomes. Providing meaningful screening and interventional tools to optimize medication use may improve treatment outcomes in these patients. Funding:UG1CA18996, U01CA233167.
Prevalence of frailty for middle-aged and older adults starting a new line of systemic cancer treatment: Is age just a number?
Authors: Pergolotti Mackenzi , Wood Kelley C , Hidde Mary , Kendig Tiffany , Williams Grant Richard , Giri Smith , Ronnen Ellen A. , Carroll Rachel 
Published: June 2022

12054 Background: Frailty is associated with adverse outcomes and increased risk of mortality for older adults (>60 years) with cancer. Geriatric assessment (GA) has gained popularity in routine cancer care as a clinical tool to screen for frailty in older adults starting a new line of cancer treatment, and to guide clinical decision making during systemic therapy. Emerging research indicates GA may also be useful to identify frailty in middle-aged adults (40-60 years) with cancer, but more research is needed. In this study, we used GA data to compare the prevalence of frailty between middle-aged and older adults starting a new line of systemic cancer treatment. Methods: Participants included adult patients with cancer due to begin a new line of systemic therapy at a multi-office community-based oncology private practice and enrolled in a clinical trial (NCT04852575). At baseline, participants completed an online version of the Cancer and Aging Resilience Evaluation (CARE) — a patient-reported GA adapted from the Cancer and Aging Research Group. Frailty score was constructed using a 44-item deficit accumulation method and categorized as frail (>0.35), pre-frail (0.2-0.35) or robust (0-0.2) using published cutoffs. We grouped participants by age, middle-aged (40-60 years) or older-aged (>60 years), then used independent t-test and chi-squared statistic to compare frailty scores (continuous) prevalence of frailty (categorical) between groups. Hypothesis testing was two sided and the level of significance was 0.05. Results: Participants ( n=96) were predominantly female (62%), Caucasian (68%) and beginning first line systemic therapy (69%) for either newly diagnosed cancer or new recurrence of disease; median time since diagnosis was 1 month. Common cancer types included: breast (34%), gastrointestinal (23%), hematologic (15%) and lung (12%). Disease stage was predominantly stage 3 (28%) or stage 4 (38%). When comparing middle-aged ( n=31, Mage = 54.74 ± 4.79, range = 41.23 – 59.98 years) vs. older adult -groups ( n=65, Mage = 70.27 ± 5.91, range = 60.64 – 84.29 years), there was no significant difference in mean frailty score ( p = 0.22) or the proportion categorized as frail vs. pre-frail vs. robust ( p = 0.32); see Table. Stage of disease and prevalence of common cancer types was similar between age groups (p>.05). Conclusions: In our cohort, middle and older aged patients who completed patient-report GA had similar prevalence of frailty before starting systemic therapy. Using the GA as a functional-age assessment to detect frailty for adults of varied ages could allow for earlier intervention aimed at impacting tolerance to therapy. Clinical trial information: NCT04852575. [Table: see text]
Retrospective analysis of healthcare disparities in Philadelphia chromosome-positive ALL: A single-institution experience of a large metropolitan area.
Authors: Bouligny Ian Michael , Tran Valerie , Zacholski Kyle , Venn Chad Michael , Alnimer Yanal Mufeed , Ho Thuy , Maher Keri Renee 
Published: June 2022

12067 Background: Philadelphia chromosome-positive (Ph+) ALL is an aggressive hematological neoplasm with a dismal prognosis. Hematopoietic stem cell transplant (HSCT) remains the standard of care for those reaching complete remission due to high relapse rates with conventional therapy alone. We have previously demonstrated findings concerning for imbalanced outcomes among racial groups in AML. In the era of TKIs targeting BCR-ABL1 in combination with conventional therapy, it is unclear whether trends noted in AML are also seen in Ph+ ALL. Thus, the purpose of this study was to investigate the impact of healthcare disparities on outcomes in Ph+ ALL with regards to access to care, response rates, toxicities, and overall outcomes. Methods: We retrospectively analyzed 59 patients with Ph+ B-ALL treated at our institution with TKIs +/- chemoimmunotherapy during January 2015 to January 2021. Baseline patient demographics were obtained, including insurance type, performance status at diagnosis, cytogenetic and molecular profiling, dates and doses of induction, toxicity, response, MRD analysis, and HSCT access and outcomes. Race was determined by patient self-report as recorded in the electronic medical record. Results: We divided 58 patients (one excluded as race was unknown) into two cohorts: 23 (39.7%) patients that identified as minorities, including African American, Hispanic/Latino, and Asian, and 35 (60.3%) identifying as White. There were no differences in baseline characteristics including age (p =.367), sex (p =.788), ECOG at diagnosis (p =.438), Charlson Comorbidity Index scores (p =.551), or presence of additional poor-prognostic mutations (p >.999). Despite this, minorities were significantly more likely to be treated with lower-intensity regimens compared to non-minorities (p =.022). Achievement of CR by MRD was approaching statistical significance favoring the non-minority cohort (60.0% versus 27.3%, p =.055). Receipt of HSCT numerically favored the non-minority cohort, approaching statistical significance (54.3% versus 26.1%, p =.056). At a median follow-up time of 3.3 y., the median OS was not reached between the two groups and there was no difference in survival between the two groups (p =.662). Conclusions: Despite similar patient-related characteristics, minority populations are more likely to be treated with lower-intensity strategies, concerning for bias in regimen selection. Achievement of CR by MRD and receipt of HSCT appeared to be numerically lower in the minority cohort. While there appeared to be no difference between the two cohorts with regards to survival during the follow-up period, it is unclear if this would be maintained with longer follow-up. These findings highlight the need for ongoing vigilance regarding physician biases and increasing the need for improving access to curative treatment for all patients.