tbuckley/cabot-search huggingface dataset:
Avelumab first-line (1L) maintenance plus best supportive care (BSC) versus BSC alone for advanced urothelial carcinoma (UC): Analysis of time to end of next-line therapy in JAVELIN Bladder 100.
Authors: Petros Grivas, Se Hoon Park, Eric Voog, Evgeny Kopyltsov, Howard Gurney, David Queiroz Borges Muniz, Frederic Rolland, Anne Birgitte Als, Begoña P. Valderrama, Jing Wang, Nuno Matos Costa, Robert J Laliberte, Alessandra Di Pietro, Thomas Powles, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2021)

4525 Background: Avelumab 1L maintenance is approved in various countries for patients (pts) with advanced UC that has not progressed with 1L platinum-based chemotherapy based on significantly prolonged overall survival (OS) seen with avelumab + BSC vs BSC alone in the phase 3 JAVELIN Bladder 100 trial. OS was prolonged despite the more frequent use of subsequent anticancer therapy in the BSC alone arm (42.3% in the avelumab + BSC arm vs 61.7% in the BSC alone arm), most commonly with immune checkpoint inhibitors (6.3% vs 43.7%, respectively). To further characterize the efficacy benefits of avelumab 1L maintenance, we report a post hoc analysis of the time to end of next-line therapy (for any reason) in the randomized trial population. Methods: In JAVELIN Bladder 100 (NCT02603432), eligible pts had unresectable locally advanced or metastatic UC without disease progression with 4 to 6 cycles of 1L gemcitabine + either cisplatin or carboplatin. The primary endpoint was OS from randomization, assessed in 2 populations: all pts and pts with PD-L1+ tumors (Ventana SP263). In this exploratory analysis, time from randomization until end of next-line treatment received after first progression (due to death or discontinuation) was assessed. Results: A total of 700 pts were randomized 1:1 to avelumab 1L maintenance + BSC or BSC alone. Among all randomized pts, time to end of next-line therapy was prolonged in the avelumab + BSC arm vs the BSC alone arm (Table). Time to end of next-line therapy was also longer in the avelumab + BSC arm vs the BSC alone arm in pts with PD-L1+ tumors (n = 358) or PD-L1− tumors (n = 270). Conclusions: Pts who received avelumab 1L maintenance + BSC had prolonged time to end of next-line treatment compared with those who received BSC alone, irrespective of PD-L1 status. These data provide further evidence of the efficacy of a maintenance approach with avelumab in pts with advanced UC that has not progressed with 1L platinum-based chemotherapy. Clinical trial information: NCT02603432. [Table: see text]
Schistosome W-Linked Genes Inform Temporal Dynamics of Sex Chromosome Evolution and Suggest Candidate for Sex Determination
Authors: Marwan Elkrewi, Mikhail A Moldovan, Marion A L Picard, Beatriz Vicoso
Journal: Molecular Biology and Evolution (2021)

Schistosomes, the human parasites responsible for snail fever, are female-heterogametic. Different parts of their ZW sex chromosomes have stopped recombining in distinct lineages, creating "evolutionary strata" of various ages. Although the Z-chromosome is well characterized at the genomic and molecular level, the W-chromosome has remained largely unstudied from an evolutionary perspective, as only a few W-linked genes have been detected outside of the model species Schistosoma mansoni. Here, we characterize the gene content and evolution of the W-chromosomes of S. mansoni and of the divergent species S. japonicum. We use a combined RNA/DNA k-mer based pipeline to assemble around 100 candidate W-specific transcripts in each of the species. About half of them map to known protein coding genes, the majority homologous to S. mansoni Z-linked genes. We perform an extended analysis of the evolutionary strata present in the two species (including characterizing a previously undetected young stratum in S. japonicum) to infer patterns of sequence and expression evolution of W-linked genes at different time points after recombination was lost. W-linked genes show evidence of degeneration, including high rates of protein evolution and reduced expression. Most are found in young lineage-specific strata, with only a few high expression ancestral W-genes remaining, consistent with the progressive erosion of nonrecombining regions. Among these, the splicing factor u2af2 stands out as a promising candidate for primary sex determination, opening new avenues for understanding the molecular basis of the reproductive biology of this group. Keywords: sex chromosomes, evolutionary strata, W-linked gene, sex determining gene, schistosome parasites.
Physical Activity, Subclinical Myocardial Injury, and Risk of Heart Failure Subtypes in Black Adults
Authors: Kershaw V Patel, Shawn Simek, Colby Ayers, Ian J Neeland, Christopher deFilippi, Stephen L Seliger, Katy Lonergan, Nicole Minniefield, Robert J Mentz, Adolfo Correa, Wondwosen K Yimer, Michael E Hall, Carlos J Rodriguez, James A de Lemos, Jarett D Berry, Ambarish Pandey
Journal: JACC Heart Failure (2021)
Polygenic prediction of atopic dermatitis improves with atopic training and filaggrin factors
Authors: Christopher H. Arehart, Michelle Daya, Monica Campbell, Meher Preethi Boorgula, Nicholas Rafaels, Sameer Chavan, Gloria David, Jon Hanifin, Mark K. Slifka, Richard L. Gallo, Tissa Hata, Lynda C. Schneider, Amy S. Paller, Peck Y. Ong, Jonathan M. Spergel, Emma Guttman-Yassky, Donald Y.M. Leung, Lisa A. Beck, Christopher R. Gignoux, Rasika A. Mathias, Kathleen C. Barnes
Journal: Journal of Allergy and Clinical Immunology (2021)
Preoperative stereotactic ablative body radiotherapy with postoperative conventional irradiation of soft tissue sarcomas: Protocol overview with a preliminary safety report.
Authors: Mariia Ebert, Sergey Novikov, Grigory Zinovev, Georgy Gafton, Svetlana Protsenko, Ivan Gafton, Mikhail Sinyachkin
Journal: Journal of Clinical Oncology (2021)

e23546 Background: Preoperative radiotherapy in patients with soft tissue sarcomas is characterized by important advantages: high precision of dose delivery, reduction of tumour volume and implantation potential, induction of immunologic response. Postoperative irradiation is associated with a reduced risk of complication, and a comprehensive radiotherapy planning in accordance with the pathologic report. Combination of pre- and postoperative irradiation gives the opportunity to use the best of both methods. Methods: from 06.2018 to 01.2021 24 patients with soft tissue sarcomas of extremities were included in the protocol (NCT04330456) and 14 cases with at least 12 months follow-up were eligible for analysis. Preoperative stereotactic ablative body radiotherapy (SBRT) was performed as 5 fraction of 7 Gy with dose reduction (5 fractions of 5 Gy) on the margins of the tumor. Postoperative radiotherapy started 5-8 weeks after the surgery and was performed as standard compartmental irradiation in 25 fractions of 2Gy. Complications were determined according to CTCAE and wound complication scales. Results: Preoperative SBRT and subsequent radical resection with tumor free surgical margins were performed in all 14 cases. Primary wound closure was mentioned in all patients. Postoperative radiotherapy started 51.8 days (range 33-99 days) days after the surgery. With a relatively short follow-up of 21.5 (13-30) months, we recorded 2 cases (14%) of severe complications (Canadian sarcoma group criteria), and there were no local recurrences. Conclusions: Our preliminary results demonstrate that the combination of preoperative SBRT and postoperative conventional radiotherapy is feasible and does not increase the risk of postoperative complications. Clinical trial information: NCT04330456.
Platinum-based chemotherapy combined with endostar in the treatment of advanced NSCLC: A real world study.
Authors: Wei Jiang, Wei Sun, Wenhui Li, Jing Gao, Hui Wang, Wei Zhou, Jing Liang, Lixiang Aa, Changhong Zhao, Luhua Wang
Journal: Journal of Clinical Oncology (2021)

e21033 Background: Recombinant human endostatin (endostar), an angiogenesis inhibitor, has been approved for the treatment of NSCLC in combination with chemotherapy in China. This study aims to evaluate real world efficacy and safety of endostar combined with platinum-based chemotherapy in the treatment of advanced NSCLC. Methods: This study retrospectively collected electronic medical record system (EMR) information of NSCLC patients (pts) who received endostar combined with platinum-based chemotherapy regiments from June 2012 to August 2019 in 7 cancer hospitals after obtaining ethical approval. Baseline characteristics, efficacy evaluation and safety data were analyzed. Tumor response was evaluated according to RECIST 1.1. Adverse events (AEs) were graded according to NCI-CTC AE 4.0. The endpoints include objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety. Results: 512 advanced NSCLC pts who received endostar combined with platinum-based chemotherapy regiments were analyzed. The median age of pts was 59.2 years. Most pts were male, accounting for 75.2%. 63.3% pts was diagnosed at stage IV. 40.0% pts was adenocarcinoma and 35.4% pts was squamous cell carcinoma. 81.4% pts received endostar combined with chemotherapy as first-line. 292 people were included in the efficacy analysis set. The ORR, DCR and median PFS were 34%, 73% and 8.2 (95% CI 6.0-13.7) months, respectively. There were no significant differences of ORR and DCR among common platinum-based chemotherapy. The most common AEs were gastrointestinal reactions (29%), bone marrow suppression (14%), and liver damage (12%). Conclusions: The real-world data confirmed the superiority of endostar plus platinum-based chemotherapy in Chinese advanced NSCLC pts, with acceptable adverse effects. Clinical trial information: ChiCTR2000035129.
U.S. budget impact analysis of an intravenousrituximab biosimilar versus subcutaneous rituximab for the treatment of non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL).
Authors: Elizabeth James, Holly Trautman, Ali McBride, Azhar Choudhry, Stephen Thompson
Journal: Journal of Clinical Oncology (2021)

e18821 Background: Rituximab-abbs is a CD20-directed monoclonal antibody and the first rituximab biosimilar approved in the US, expected to significantly reduce drug acquisition costs. This budget impact model (BIM) estimated budgetary impact of replacing a proportion of rituximab/hyaluronidase human subcutaneous injection (SC-R) utilization for NHL (diffuse large B-cell lymphoma [DLBCL], follicular lymphoma [FL]) and CLL with rituximab-abbs (IV-R-BIOSIM). The objective was to project incremental cost differences between IV-R-BIOSIM and SC-R over one year for a hypothetical 5-million-member US healthcare insured (Medicare) population. Methods: An illustrative BIM was developed to estimate 1-year drug and administration costs for a one-quarter shift in SC-R market utilization to IV-R-BIOSIM, with equal efficacy and safety assumed. Values for epidemiology, market share, drug dosing, administration, and costs were derived from scientific literature, product labels, and publicly available cost resources. Infused rituximab (IV-R) dosing assumed a mean body surface area (BSA) of 1.8m 2 . Annual dose counts of IV-R-BIOSIM or SC-R per patient were: 10 untreated FL with maintenance; 8 untreated FL (without maintenance), relapsed/refractory FL, or untreated DLBCL; 6 CLL. IV-R infusion duration was 3 hours. Drug acquisition and infusion/subcutaneous administration costs were from 2020 Average Sales Price pricing file and Centers for Medicare and Medicaid Services Physician Fee Schedule. SC-R costs included an initial IV-R originator dose. Patient cost share was based on 2020 Medicare Part B 20% cost-share for office visits and drugs. Univariate sensitivity analyses were conducted. A scenario analysis used 2-year dosing to estimate costs for further FL maintenance treatment. Results: For a 5-million-member insured population, an estimated 972 patients would receive rituximab for NHL or CLL; 49 would receive SC-R. Estimated total incremental savings for one year for a 13-patient shift from SC-R to IV-R-BIOSIM were $57,864, equating to $0.02 per enrolled member per year (PMPY). Per-patient incremental annual savings with IV-R-BIOSIM for one year ranged between $2,359–$8,186 (Table). The model was most sensitive to low or high BSA dosing and proportion of patients with CLL. Conclusions: This BIM estimated annual savings of over $57,000 ($0.02 PMPY) for a 5-million-member US payer following a 25% shift of current SC-R use to IV-R-BIOSIM. These findings demonstrate the potential economic benefits of IV-R-BIOSIM vs SC-R that may result in expanded access to rituximab therapy.[Table: see text]
The impact of COVID-19 on delivery of systemic anti-cancer treatment in urological cancer patients: A comparison with 2019 data from Guy’s Cancer Center.
Authors: Christina Karampera, Muhammad Khan, Beth Russell, Charlotte Moss, Maria J Monroy-Iglesias, Saoirse Dolly, Kiruthikah Thillai, Debra Hannah Josephs, Elias Pintus, Sarah Rudman, Mieke Van Hemelrijck, Deborah Enting
Journal: Journal of Clinical Oncology (2021)

e17057 Background: The provision of cancer services has been strongly impacted by the outbreak of SARS-CoV-2. Our Cancer Centre in South-East London treats approximately 8,800 patients annually and is one of the largest Comprehensive Cancer Centres in the UK. When dealing with the second wave of COVID-19, it is important to further evaluate the safety of cancer treatments whilst balancing the risks of COVID-19 infection and complications. Here, we report on the patient/tumour characteristics of those patients undergoing SACT for a urological cancer diagnosis during the first wave, so as to help establish clinical guidelines for the management of these patients in a SARS-CoV-2 epidemic. Methods: All urological cancer patients receiving at least one SACT between 1 st March- 31 st May 2020 (COVID-19 period) were compared to the same timeframe in 2019. SARS-CoV2 infection was defined as a positive RT-PCR test; patients with symptoms or radiological changes alone were excluded. As part of Guy’s Cancer Cohort, we collected information on demographics, and cancer type, stage, and treatment. Results: A total of 455 patients (305 prostate, 102 renal, 38 bladder, and 10 testicular) received SACT in 2020 as compared to 535 (353 prostate, 129 renal, 37 bladder, and 15 testicular) in 2019 (15% overall decline). Patient characteristics in terms of demographics were fairly comparable, with 10% female patients in 2019 and 9% in 2020; 49% aged 70+ vs 45%; and 77% in the low socio-economic category vs 78%. There was an increase in patients with stage 4 (89% vs 95% in 2020) and a slight change in distribution of SACT types (2019 vs 2020): chemotherapy (18% vs 14%), immunotherapy (7% vs 10%), biological or targeted (63% vs 66%), combination of biological/targeted (6% vs 5%), other combinations (5% vs 5%). The proportion of SACT delivered as part of radical treatment declined from 3% to 0.2% in 2020. A total of 5 patients (1%) developed COVID-19 (2 prostate, 2 renal, and 1 bladder). All were male and aged 60+; three had 2+ comorbidities. One patient was on immunotherapy and four on biological or targeted treatment. Four patients had severe pneumonia and one died of their COVID-19 (bladder cancer). Conclusions: Whilst there was a decline of number of patients receiving SACT during COVID-19, we were still able to provide a safe high-quality urological cancer SACT pathway during the peak of the COVID-19 pandemic, with very few COVID-19 positive patients. In a next step we will evaluate oncological outcomes at 6 months follow-up
Analyzing treatment patterns and time to the next treatment in chronic lymphocytic leukemia real-world data using automated temporal phenotyping.
Authors: Kyeryoung Lee, Zongzhi Liu, Meng Ma, Yun Mai, Christopher Gilman, Minghao Li, Mingwei Zhang, Tommy Mullaney, Qi Pan, Rong Chen, Eric Schadt, Xiaoyan Wang
Journal: Journal of Clinical Oncology (2021)

e19512 Background: Targeted therapy is an important treatment for chronic lymphocytic leukemia (CLL). However, optimal strategies for deploying small molecule inhibitors or antibody therapies in the real world are not well understood, largely due to a lack of outcomes data. We implemented a novel temporal phenotyping algorithm pipeline to derive lines of therapy (LOT) and disease progression in CLL patients. Here, the CLL treatment pattern and time to the next treatment (TTNT) were analyzed in real-world data (RWD) using patient electronic health records. Methods: We identified a CLL cohort with LOT from the Mount Sinai Data Warehouse (2003-2020). Each LOT consisted of either a single agent or combinations defined by NCCN CLL guidelines. We developed a natural language processing (NLP)-based temporal phenotyping approach to automatically identify the number of lines and therapeutic regimens. The sequence of treatment and time interval for each patient were derived from the systematic treatment data. Time to event analysis and multivariate (i.e., age, gender, race, other treatment patterns) Cox proportional hazard (CoxPH) models were used to analyze the patterns and predictors of TTNT. Results: Four hundred eleven CLL patients received 1 to 7 LOTs. Ibrutinib was the predominant 1 st LOT (40.8% of patients) followed by anti-CD20-based antibody therapies and chemotherapy in 30.6 and 19.2% of patients, respectively, followed by Acalabrutinib, Venetoclax, and Idelalisib in 3.4, 2.7, and 0.7% of patients, respectively (Table 1). The 2 nd to 5 th LOT showed the same or similar trends. We next analyzed the TTNT in the 1 st line of each therapeutic class. Acalabrutinib resulted in a longer median TTNT than Ibrutinib. Both Acalabrutinib and Ibrutinib showed longer TTNT compared to Venetoclax (median TTNTs were 742 and 598 vs. 373 days: HR = 0.23, p=0.015 and HR = 0.48, p=0.03, respectively). In addition, patients with age equal to or older than 65 showed longer TNNT (HR=0.16, p=0.016). Conclusions: Our result shows the potential of RWD usage in clinical decision making as real-world evidence reported here is consistent with results derived from clinical trial data. Linking this study to genetic data and other covariates affecting treatment outcomes may provide additional insights into the optimal sequences of the targeted therapies in CLL. Table 1: Therapeutic class and patient numbers (%) in each line.[Table: see text]
Change in the comprehensive geriatric assessment scores at day 30 post-cancer treatment in geriatric oncology patients.
Authors: Toufic Tannous, Dany Debs, Erkan Ceyhan, Ponnandai Sadasivan Somasundar
Journal: Journal of Clinical Oncology (2021)

12048 Background: The comprehensive geriatric assessment (CGA) is a multidimensional tool for assessing the functional, cognitive, nutritional and frailty status of patients above 65 years of age with cancer. It includes several components: patient health questionnaire (PHQ-9), timed up and go (TUG), mini mental status exam (MMSE), mini nutritional assessment (MNA), Poly Pharmacy (PP), activities of daily living (ADL), instrumental activities of daily living (IADL) and comorbidities. Previous studies showed that some baseline CGA scores (pre-treatment) are predictors of mortality. However, to our knowledge, there has been no study evaluating the change of those scores in response to treatment at different time periods. We sought to evaluate the evolution of the CGA scores after 30 days post-treatment. Methods: We conducted a single institution, prospective cohort registry of patients with solid cancers aged 65 or older in Rhode Island from 2013-2018. All patients underwent a CGA before starting treatment (day 0) and post-treatment (day 30). Treatment included surgery, chemotherapy, radiation, or any combination. Baseline demographic characteristics as well as CGA components were abstracted. TUG, MMSE, PHQ-9, IADL, PP, BMI, MNA and ADL performed at day 0 and 30 were collected. The mean for each score was obtained at both days. Student T test was used to test for significance for nominal data and Chi square test for ordinal data. A P value of less than 0.05 was deemed statistically significant. Results: 283 patients were enrolled. The mean age was 76 (+-6.86) of which 54% were females. 92% of patients were white and 8% were black. Colorectal and lung cancer were among the most common. The mean Charleston comorbidity index was 12.3 (+-3.2). The mean BMI decreased from 26.92 (+-5.84) at day 0 to 26.1 (+-5.45) at day 30 (p &lt; 0.01). The mean IADL decreased from 5.93 (+-2.03) to 5.2 (+-2.12) (p &lt; 0.01). At day 0, one patient had impaired ADLs compared to 7 patients at day 30 (p = 0.03). PHQ-9, MMSE, MNA, TUG and PP scores did not significantly differ at day 30 post treatment (Table). Conclusions: The ADL, IADL and BMI scores showed a statistically significant change at Day 30, indicating deteriorating scores in those patients. Our study showed that ADL, IADL and BMI were the only variables that worsened at day 30 post-treatment compared to PHQ-9, MMSE, MNA, TUG and PP. This suggests that they may be used as early markers of clinical deterioration in geri-onc patients undergoing treatment. More studies are needed to assess their prognostic significance.[Table: see text]
<i>TP53</i> Disruption in Chronic Lymphocytic Leukemia Under Ibrutinib: More is Worse?
Authors: Riccardo Bomben, Antonella Zucchetto, Massimo Gentile, Valter Gattei
Journal: Clinical Cancer Research (2021)

Abstract Patients with chronic lymphocytic leukemia carrying a single TP53 hit (chromosome 17p deletion or single TP53 mutation) demonstrate excellent progression-free survival and overall survival on ibrutinib compared with cases harboring multiple TP53 hits. Testing TP53 deletion/mutation combining FISH and deep next-generation sequencing should be performed for a correct patient evaluation. See related article by Brieghel et al., p. 4531