bluuebunny/crossref_metadata_2025_split huggingface dataset:
Confirmed tumor response by molecular subtype in patients with metastatic breast cancer: Sub-analysis from a phase 3 clinical study comparing oral paclitaxel and encequidar to IV paclitaxel.
Authors: Umanzor Funez Gerardo Antonio , Rugo Hope S. , Umanzor Jorge , Barrios Francisco , Vasallo Rosa , Chivalan M , Bejarano Suyapa A. , Ramirez Julio Roberto , Fein Luis Enrique , Kowalyszyn Ruben Dario , Wang Hui , Cutler David 
Published: June 2021

1073 Background: Paclitaxel, a foundation treatment in MBC, is hydrophobic and must be formulated for IV administration with Cremophor EL, increasing the risk of infusion reactions and necessitating pre-treatment with corticosteroids and antihistamines. Paclitaxel cannot be administered orally because it is a substrate for P-gp. The oral bioavailability of paclitaxel is improved when administered 1 hour after the highly selective, potent, and minimally absorbed P-gp inhibitor encequidar. As oral paclitaxel is Cremophor-free there is no need for pretreatment for infusion reactions. While targeted therapies have improved outcomes in patients with HER2+ tumors there is still an unmet need for therapies that prolong survival with reduced toxicity across all tumor subtypes. Methods: A phase 3, open-label, randomized, multicenter study in women with histologically- or cytologically-confirmed MBC for whom treatment with IV paclitaxel monotherapy had been recommended by their oncologist randomized 402 patients 2:1 to either oral paclitaxel and encequidar (oPac+E) or IV paclitaxel (IVPac). Oral paclitaxel 205 mg/m2 was administered once daily for 3 consecutive days, weekly. Encequidar 12.9 mg was administered 1 hour before each dose of oral paclitaxel. IV paclitaxel 175 mg/m2 was infused over 3 hours on day 1 of every 3 weeks. Results: In the ITT population oPac+E was superior to IV paclitaxel with a confirmed tumor response rate of 35.8% vs 23.4% for IVPac: a difference of 12.4% (p = 0.0107). A post-hoc subgroup efficacy analysis was conducted based on tumor subtypes, however, the study was not powered to detect statistical differences within these subgroups. Patients in the HR+/HER2- subgroup had a better tumor response to oPac+E (44.8% vs 21.4% IVPac-response rate difference of 23.4%) as did patients in the TNBC (30.5% vs 20.2%-response rate difference of 10.3%) subgroup. Responses were similar (49% vs 47.4% IVPac) in the HER2+ subgroup. Patients with unknown HER2 status receiving oPac+E had a 58.8% response rate vs 14.3% with IVPac (response rate difference of 44.5%). Conclusions: oPac+E is the first oral taxane to demonstrate superiority in radiologically confirmed tumor response rate compared to IVPac in a group of 402 women with metastatic breast cancer. Patients with HR+/HER2-, TNBC, and Unknown subtypes responded considerably better to oPac+E vs IVPac—especially the HR+/HER2- subtype which represented 63% of the patients treated with oPac+E and 55% of the patients treated with IVPac. Clinical trial information: NCT 02594371 .
Trends in female representation in clinical practice guidelines (CPGs) among major cancer organizations.
Authors: Chengappa Madhuri , Go Ronald S. , Poonacha Thejaswi K. 
Published: June 2021

11006 Background: While women representation and sex disparities in National Comprehensive Cancer Network (NCCN) and European Society of Medical Oncology (ESMO) has been studied in a limited set of CPGs, the sex representation and disparity trend over time among all NCCN and ESMO CPG panelists has not been studied. Our study evaluates the current sex disparities and female representation for all NCCN and ESMO CPGs as of 2020 and compared it to the 2010 CPGs of both organizations. Methods: The 2010 and 2020 version of NCCN and ESMO CPGs were examined from their respective websites and archives. We catalogued the number of female versus male panelist for each CPG. We discerned the sex of the panelists based on google search and the panelists’ affiliated institutional websites. Results: 60 NCCN (2020), 51 NCCN (2010), 78 ESMO (2020) and 55 ESMO (2010) CPGs inclusive of all cancers by site, detection prevention and risk reduction, supportive care, and guidelines for specific population were reviewed. NCCN 2020 CPGs had 55.5% female representation. 35 (58%) NCCN CPGs had predominant female representation (>50% of the members being female) whereas 24 CPG (40%) were male predominant (>50% of the members being male). Solid tumors had 24 CPGs with male predominance and hematological malignancies had 14 CPGs with female predominance. Cancers specific to women had higher proportion of female panelist. NCCN 2010 CPGs had 27.1% female representation. Both solid tumors and hematological malignancies had male predominance (82% and 75% respectively). Breast cancer screening, palliative care and older adult oncology CPGs were female predominant. ESMO 2020 had 27.8% female representation. Both solid tumors (37 CPGs) and hematological malignancies (17 CPGs) had predominant male representation (72% and 85% respectively). Breast and ovarian cancer CPGs were female predominant. ESMO 2010 had 23.2% female representation. Male representation was predominant in both solid tumors (35 CPGs) and hematological malignancies (9 CPGs). Breast, cervical and ovarian cancer CPGs were female predominant. Conclusions: Over the last decade, proportion of female panelists in NCCN CPGs has doubled with more than 50% representation among its 60 CPGs, indicating adequate representation of women. In ESMO, although there has been a significant improvement in female representation in hematological malignancies over time, it continues to have overall female underrepresentation (<30%).[Table: see text]
Corresponding about death: Analyzing letters from patients with cancer to medical students.
Authors: Zhang Tianyi , Tilahun Mekaleya , Perlis Cynthia , Brondfield Sam 
Published: June 2021

11021 Background: Clinicians frequently discuss death and dying with patients who have cancer. However, the doctor-patient hierarchy and the unfamiliar clinical environment may prevent these patients from discussing death and dying authentically. Patients may feel more comfortable expressing themselves when given the time and space to write at home. Firefly, an award-winning program at UCSF, facilitates written correspondence between patients with cancer and medical students over the course of one year. Firefly’s archive contains thousands of patient letters and constitutes a unique resource for analyzing authentic patient expression outside of the clinical context. The aim of the current study is to improve curricula pertaining to severe illness and end-of-life by providing educators with an analysis of authentic patient perspectives about death and dying expressed in these letters. Methods: We (two medical students, an expressive artist, and an oncologist) read all Firefly letters written by patients between 2014 and 2019 and identified 12 patients whose letters meaningfully discussed death or dying. We performed a thematic analysis of these letters using the Buckman three-stage model of dying as a reference. Results: Four themes emerged: turmoil; grief; making peace; and past, present and future. The first three themes aligned with the Buckman stages. The fourth theme—past, present and future—spanned the three stages and also elaborated the Buckman model by describing multiple paths that patients may take after passing through these stages. Conclusions: The authentic ways in which patients with cancer discussed death and dying in their letters provided deep insight into their coping process. The Buckman model appears useful for framing death and dying from the patient perspective but may not fully reflect modern oncologic care in which many patients live for years beyond a severe or terminal diagnosis. Educators can use the identified themes to shape medical school curricula pertaining to severe illness and end-of-life care.
Improving feedback for hematologists and oncologists in training.
Authors: Schlam Ilana , Sewaralthahab Sarah , Peravali Monica , Chou Calvin , Gilligan Timothy D. , Veytsman Irina , Shenoy Aarthi G. 
Published: June 2021

11025 Background: Feedback is an integral part of the learning process, allowing learners to remain on course in reaching competence in clinical, research, and interpersonal skills. However, the impact of teaching feedback during hematology-oncology training has not been studied. We aimed to identify barriers in delivering and receiving high-quality feedback in our fellowship program and to create a curriculum aimed at teaching fellows and faculty how to engage in more effective feedback conversations. Methods: This pilot study aimed at determining and addressing perceived barriers to high-quality feedback in the hematology-oncology fellowship program. A pre-intervention questionnaire, consisting of Likert scale and open-ended questions, was administered to identify barriers to giving feedback and to assess satisfaction with the quality of feedback received in our fellowship program. The results of the baseline questionnaire were utilized to build a virtual interactive three-session workshop provided by the ASCO Quality Training Program in which the importance of feedback and methods of providing effective feedback were taught. Topics included feedback set-up, low-inference observation, and a structured approach to reinforcing and modifying feedback. One month after the intervention the participants completed a follow up questionnaire. This project was developed through the ASH Medical Educators Institute. Results: Each questionnaire was completed by 11 participants. The two main barriers to high-quality feedback identified were the discomfort with both giving and receiving feedback, and the lack of protected time. At baseline only 54% of the participants reported they were comfortable giving feedback, increasing to 81% post- intervention. Pre-intervention, 81% of participants reported they did not have protected time for feedback, decreasing to 64% after the intervention and institution of weekly protected time for feedback. Half of the participants reported that the feedback was not actionable in the initial questionnaire, decreasing to 10% post-intervention. Overall, fellows reported that their feedback was mostly focused on notes, followed by presentations and interpersonal skills. Faculty reported that most of the feedback they received was about time management and patient care. Conclusions: This pilot study helped address a major barrier to improvement and growth within our training program and confirmed that feedback skills must be taught and practiced. A 6-hour virtual workshop showed tangible results in the satisfaction with and quality of feedback given to both fellows and faculty. Our findings are salient as we completed the intervention during the COVID pandemic. Limitations of the study include its single-institutional design and sample size. A major challenge anticipated is sustainability, which will be addressed by maintaining periodic lectures and assigning protected time for feedback.
Genomic alterations and associated pathway abnormalities in Ewing sarcoma.
Authors: Rock Adam , Chow Warren Allen , Uche An , Millis Sherri Z. 
Published: June 2021

11532 Background: Ewing Sarcoma (ES) is an aggressive, translocation-associated, bone cancer associated with a poor prognosis in the recurrent or metastatic setting. ES is identified by the canonical balanced reciprocal chromosomal translocation involving EWSR1 and ETS transcription factors. Secondary somatic alterations in ES are rarely described and genomic alterations (GA) affecting various molecular pathways may work synergistically with ETS-FL1 translocations to promote oncogenesis. Alterations in fibroblast growth factor receptor 4 (FGFR4), a receptor tyrosine kinase protein that functions in cellular processes, have been observed to affect carcinogenesis. Moreover, the FGFR4-Gly388Arg (G388R) single nucleotide polymorphism (SNP) is found to increase the risk of cancer with mouse embryonic fibroblasts derived from knock-in strain of homologous Fgfr4 G385R mice exhibiting a transformed phenotype. We sought to further evaluate the frequency of FGFR4 G388R SNP in relation to other identifiable pathway alterations observed with Comprehensive Genomic Profiling (CGP). Methods: Next generation sequencing (NGS) analysis was obtained in the context of clinical care with clinical status, outcomes, and source acquisition (primary tumor, metastasis, or recurrence) unknown to Foundation Medicine. CGP, FoundationOne Heme, evaluated GAs including base substitutions, indels, amplifications, copy number alterations, gene fusions and rearrangements. 189 samples were assayed by hybrid-capture based CGP, including 406 DNA-sequenced genes in addition to 265 RNA-sequenced genes commonly reported to be rearranged in cancer, as previously described. Tumor mutational burden was assessed from a minimum 1.4 Mb sequenced DNA. Microsatellite instability (MSI) status was determined by a novel algorithm analyzing 114 specific loci. Results: The median age of evaluated patients was 20 (range 0-70) with the number of alterations averaging 7 per patient. Pathways noted to be altered in the presence of FGFR388R SNP occurred frequently with the following pathways most observed: MAPK (33%), WNT (32%), NOTCH1 (20%), HRR (19%), Histone/chromatin remodeling (18%). FGFR388R SNP was observed in more than half (51%) of evaluated samples. Most affected pathways irrespective of FGFR388R SNP status included: MAPK (n = 89), HRR (n = 75), and PIK3 (n = 64). All evaluated samples were TMB low ( < 10 mut/mb) and Microsatellite Stable. Conclusions: Secondary GAs affecting major pathways were observed in high frequency, often co-occurring with the FGFR4 G388R SNP. Secondary alteration of known oncogenic pathways may contribute to sarcoma formation in ES potentially informing further therapeutic strategies in the future.
Recurrence and disease-specific survival after 10-year disease-free interval in patients with primary retroperitoneal liposarcoma: Implications for long-term surveillance.
Authors: Eckardt Mark Archer , Graham Danielle S. , Kadera Brian E. , Klingbeil Kyle D. , Nelson Scott D. , Dry Sarah M. , Kalbasi Anusha , Singh Arun S. , Chmielowski Bartosz , Eilber Frederick R. , Crompton Joseph G. , Eilber Frederick C. 
Published: June 2021

11546 Background: Surveillance imaging of patients with retroperitoneal liposarcoma (RP-LPS) following surgical resection is based on a projected risk of locoregional and distant recurrence. The duration of surveillance is not well defined as the long-term natural history of RP-LPS after treatment is poorly understood. We evaluate a cohort of RP-LPS patients—without evidence of disease 10 years following initial resection—to assess the long-term risk of recurrence and disease-specific survival (DSS). Methods: The prospectively maintained UCLA Sarcoma Database was used to identify RP-LPS patients who demonstrated 10-year progression-free survival (10yr-PFS) after initial diagnosis and treatment. Patients in the 10yr-PFS cohort were subsequently evaluated for recurrence and DSS. Time intervals start at date of initial surgical resection. Cox proportional hazards models were used to determine factors associated with recurrence and DSS. Results: From 1972-2010, 76 patients with RP-LPS had at least 10 years of follow-up. Of these, 37 (49%) demonstrated 10yr-PFS. Median follow-up was 15 years (range 10-35 years). Among the 10yr-PFS patients, 43% (16/37) developed a recurrence >10 years after the initial surgery, and 19% (7/37) died of disease. Neither long-term recurrence nor DSS were significantly associated with age, sex, tumor size, LPS subtype, surgical margin, or peri-operative treatment with radiation or chemotherapy (Table). Conclusions: Patients with primary RP-LPS treated with surgical resection +/- multimodality therapy have a long-term risk of recurrence and disease-specific death that is unacknowledged by current surveillance imaging guidelines. Among the patients with a 10yr-PFS, 43% developed a recurrence and 19% died of disease. These findings suggest a need for lifelong surveillance imaging in patients with RP-LPS.[Table: see text]
Patient reported outcomes in patients with desmoid type fibromatosis.
Authors: GARG VIKAS , Rastogi Sameer , Barwad Adarsh , Panday Rambha , Bhoriwal Sandeep Kumar , Dhamija Ekta 
Published: June 2021

11574 Background: Desmoid type fibromatosis (DTF) is a rare benign neoplasm with infiltrative growth and high local recurrences. Due to long disease course, unpredictable growth pattern, and low mortality, using only survival outcomes may be inappropriate. In this study we assessed the impact of DTF on health related quality of life (HRQoL). Methods: This was a cross-sectional study done in patients with DTF. The study participants were asked to fill the EORTC QLQ-C30, GAD-7 and PHQ- 9 q uestionnaires to assess HRQoL, anxiety and depression . Outcomes were also compared with healthy controls. Results: 204 subjects (102 DTF patients and 102 healthy controls) were recruited. Study parameters have been summarized in Table. Appendicular skeleton (limbs + girdle) was most commonly involved in 59 % patients and abdominal wall or mesentery was involved in 22.5 %. Patients have received median of 2 lines of therapy. 54 % patients were currently on sorafenib and 41 % were under active surveillance. Mean global health status in DTF patient 65.58 ± 22.64, was significantly lower than healthy controls. Similarly, DTF patients scored low on all functional scales except cognitive functioning. Symptom scale showed significantly higher symptom burden of fatigue, pain, insomnia and financial difficulties. Anxiety & depression was observed in 39.22 % and 50 % of DTF patients respectively. DTF patients had higher rates of mild, moderate and severe anxiety and depression compared to healthy controls. No difference was observed based on site of disease. Conclusions: DTF patients have significant symptom burden, poor functioning, and heightened anxiety and depression. Patient reported outcomes should be routinely used to assess treatment efficacy in DTF patients.[Table: see text]
Characteristics of elderly-specific oncology trials registered in ClinicalTrials.gov.
Authors: Wu Bian , Yang Yun , Tang Yun , Zheng Yongqiang , Xie Mingxing , Yang Kunyu , Wu Gang 
Published: June 2021

12040 Background: Clinical trials dedicated to the elderly cancer patients are essential to help to define optimal cancer therapy for this rapidly growing population. Our study aimed to analyze the characteristics and the evolution of elderly-specific oncology trials registered in ClinicalTrials.gov. Methods: A dataset of 61120 oncology trials registered in ClinicalTrials.gov between Jan 1th, 2000 and Dec 17th, 2019 was downloaded. Interventional trials were identified and systematically reviewed to validate classification into elderly-specific (at least using a chronological landmark to define the elderly) and age-unspecified trials. Cancer type and other registration information were extracted. Characteristics of elderly-specific trials were compared with characteristics of age-unspecified trials. Chronological shifts in elderly-specific trials between 2000 to 2009, and 2010 to 2019 were analyzed. Results: Of the 49273 trials eligible for analysis, only 791 (1.6%) were elderly-specific. The most frequently used threshold to define the old was 60 years (36%), followed by 70 years (28%) and 65 years (26%). More than half of the elderly-specific trials were phase 2 (56.8%) trials and enrolled 100 or fewer participants (59.4%). Compared with age-unspecified trials, elderly-specific trials were less likely to be funded by industry (28.3% vs 37.1%; p < 0.001), and more likely to be conducted in Europe (42.1% vs 24.5%, p < 0.001). During the two time periods between 2000 to 2009, and 2010 to 2019, the proportion of elderly-specific trials of all the oncology trials remained stable (1.57% vs 1.62%). The proportion of treatment-oriented trials decreased from 91.9% to 71.4% (p < 0.001) while supportive care-oriented trials increased from 1.9% to 13.2% (p < 0.001). Industry-funded elderly-specific trials decreased from 34.0% to 25.6% (p = 0.014). Concerningly, the use of clinically meaningful end points in elderly such as disease-specific survival, patient-reported outcomes (PROs) and functional status as a primary end point were uncommon (0.5%, 8.0%, and 6.9%, respectively). However, the use of PROs as a primary end point tended to increase in the second time period, from 2.4% to 10.5% (p < 0.001). There was no correlation between the number of trials for a given cancer type and relative incidence and mortality. 336/791 (42.5%) of the trials were conducted for patients with blood cancer, although the incidence and mortality of blood cancer were relatively low. The most common solid cancer types were breast cancer (13.9%), lung cancer (10.0%), and colorectal cancer (7.8%). Conclusions: Although the majority of all new cases of cancer occur in the elderly population, elderly-specific trials account for only a minority of all oncology trials. Our study helps us to better understand the current state of elderly-specific trials and provides insights for future development that can improve the care of elder patients with cancer.