tbuckley/cabot-search huggingface dataset:
An optimized mathematical model for cancer patient care planning in the COVID-19 era.
Authors: Isabel Blancas, David Martínez-Rodríguez, Fernando Rodríguez-Serrano, Rafael Jacinto Villanueva, Jose Manuel Garrido
Journal: Journal of Clinical Oncology (2021)

e18663 Background: The COVID-19 pandemic has threatened to collapse hospital and Intensive Care Unit (ICU) services, and it seems to limit the care of oncologic patients. The objective was to develop a mathematical model designed to predict the hospitalization and ICU admission demands due to COVID-19 to forecast the availability of hospital resources for the scheduling of oncological surgery and medical treatment that require hospitalitation or possible use of ICU services. Methods: We have implemented a SEIR model designed to predict the number of patients requiring hospitalization and ICU admissions for COVID-19. We evaluated the model using the number of cases registered in the hospitals of the province of Granada (Spain), that altogether cover 914,678 inhabitants. Calibration was performed using data recorded between March 15 and September 22, 2020. After that, the model was validated by comparing the predictions with data registered between September 23 and November 7, 2020. Besides, we performed a predictive analysis of scenarios regarding different possible sanitary measures. Results: Using patient registered data we developed a mathematical model that reflects the flow among the different sub-groups related to COVID-19 pandemics (Table). The best algorithm that fitted the disease dynamics was Particle Swarm Optimization, that minimized the difference between model output and real data used to calibrate the model. The validation phase showed the accuracy of the predictions, especially concerning trends in hospitalizations and ICU admissions. The different scenarios modelled on November 10, 2020 allowed us to predict the evolution of the pandemic until July 1, 2021, and to detect the peaks and valleys of disease prevalence. Conclusions: The mathematical model presented provides predictions on the evolution of COVID-19, the prevalence and hospital or ICU care demands. The predictions can be used to detect periods of greater availability of hospital resources that make it possible to schedule the oncologic surgery and intensify the care for oncologic patients. Furthermore, our model can be adapted to other population by recalibrating the model according to demographic data, the local evolution of the pandemic and the health policies. [Table: see text]
Wireless Power Delivery Techniques for Miniature Implantable Bioelectronics
Authors: Amanda Singer, Jacob T. Robinson
Journal: Advanced Healthcare Materials (2021)

Progress in implanted bioelectronic technology offers the opportunity to develop more effective tools for personalized electronic medicine. While there are numerous clinical and pre-clinical applications for these devices, power delivery to these systems can be challenging. Wireless battery-free devices offer advantages such as a smaller and lighter device footprint and reduced failures and infections by eliminating lead wires. However, with the development of wireless technologies, there are fundamental tradeoffs between five essential factors: power, miniaturization, depth, alignment tolerance, and transmitter distance, while still allowing devices to work within safety limits. These tradeoffs mean that multiple forms of wireless power transfer are necessary for different devices to best meet the needs for a given biological target. Here six different types of wireless power transfer technologies used in bioelectronic implants-inductive coupling, radio frequency, mid-field, ultrasound, magnetoelectrics, and light-are reviewed in context of the five tradeoffs listed above. This core group of wireless power modalities is then used to suggest possible future bioelectronic technologies and their biological applications.
Association of a very high tumor mutational load with increased CD8+ and PD-1+ T-cell infiltration and improved clinical outcomes to PD-(L)1 blockade across different PD-L1 expression levels in non-small cell lung cancer.
Authors: Biagio Ricciuti, Kathryn Cecilia Arbour, Joao Victor Machado Alessi, Navin Mahadevan, James Lindsay, Rileen Sinha, Natalie I. Vokes, Gonzalo Recondo, Giuseppe Lamberti, Hira Rizvi, Giulia Costanza Leonardi, Andrew J. Plodkowski, Kristen Felt, Michael Tolstorukov, Pasi A. Janne, Eliezer Mendel Van Allen, Lynette M. Sholl, Scott J. Rodig, Matthew D. Hellmann, Mark M. Awad
Journal: Journal of Clinical Oncology (2021)

9018 Background: Although high TMB correlates with improved outcomes to immune checkpoint inhibitors (ICI) in patients (pts) with non-small cell lung cancer (NSCLC), an optimal TMB cutoff to discriminate cancers most likely to respond to ICI has not been identified. Whether TMB impacts outcomes to ICI in different PD-L1 levels subgroups is also unclear. Methods: Unbiased recursive partitioning (URP) was used to identify an optimal TMB cutoff for objective response rate (ORR) in two independent cohorts of pts with NSCLC treated with ICI at DFCI and MSKCC. TCGA was interrogated to find differences in tumor immune cell subsets according to the TMB cutoff identified. Multiplexed immunofluorescence (IF) for CD8, PD-1, PD-L1, Foxp3, and CK7 was also performed on NSCLC samples at the DFCI. Results: In the DFCI (N=686) and MSKCC (N=672) cohorts, URP found an optimal TMB cutoff for ORR at 19 mutations/megabase (mut/Mb), corresponding to the ̃90th percentile in each cohort. Median progression-free (PFS) and overall survival (OS) were significantly longer in NSCLCs with TMB ≥19 mut/Mb vs &lt;19 mut/Mb, in both cohorts (Table). After harmonizing TMB between DFCI OncoPanel and MSK-IMPACT NGS platforms, URP confirmed an optimal TMB cutoff for ORR at the 90th percentile in the combined cohort, which also associated with longer PFS/OS to ICI (Table). A TMB ≥90th percentile correlated with longer PFS/OS to ICI among NSCLCs with PD-L1 levels ≥50% and 1-49%, and longer PFS among those with PD-L1 &lt;1% (Table). Cell subset transcriptome analysis from the TCGA showed higher proportions of CD8+ T cells (P=0.02) and M1 macrophages (P&lt;0.01) among NSCLCs with a TMB ≥ vs &lt;90th percentile. IF confirmed increased CD8+, CD8+ PD1+ T-cell infiltration (P&lt;0.01), and increased CD8+/Foxp3+ ratio in NSCLC with very high TMB Conclusions: A very high TMB is associated with better outcomes to ICI and a distinct immunophenotype in NSCLC. Rational integration of TMB and PD-L1 expression may identify NSCLCs most likely to respond to ICI.[Table: see text]
Expression of multidrug resistance marker MDR1 in patients with ovarian cancer and its possible predictive significance.
Authors: Elena P. Ulianova, Darya Yu. Yakubova, Aleksandr B. Sagakyants, Galina V. Zhukova, Evgeniya M. Nepomnyashchaya, Anna P. Menshenina, Oksana G. Shulgina, Anna Yu. Ardzha, Oksana E. Zhenilo, Ekaterina V. Verenikina
Journal: Journal of Clinical Oncology (2021)

e17530 Background: Despite the progress made in diagnosis and treatment, ovarian cancer (OC) is still the third most common genital cancer. Poor results of therapy for various forms of OC stimulate the search for fundamentally new approaches to the treatment. One of the main reasons for resistance to chemotherapeutic agents includes multidrug resistance (MDR) of tumor cells. The most characterized of its various mechanisms is the elevated activity of the ABC family protein - ABCB1 (Pgp or MDR1). The purpose of the study was evaluation of the expression of this ABC transporter as a predictive factor in platinum-containing chemotherapy in OC patients. Methods: 100 patients aged 29-79 years with advanced stage IIIC - IV OC with/without ascites were recruited between 2016 and 2020. Depending on the treatment results, patients were divided into 2 groups: group 1 (n = 59) - patients with platinum sensitivity; group 2 (n = 41) - patients with platinum resistance during the treatment or within 6 months after its completion. IHC analysis was performed using rabbit polyclonal anti-MDR1 antibodies (Affinity Biosciences) diluted 1:600 and the Reveal Polyvalent HRP-DAB Detection System. The percentage and the intensity of staining were assessed: 0, 1+ weak, 2+ moderate, 3+ strong. MDR1 expression was considered positive when staining was detected in more than 10% (cut-off) tumor cells with intensities of 2+ and 3+. Statistical analysis of results was performed in the Statistica 13.0 program (StatSoftInc., USA). Results: Patients with MDR1+ prevailed in group 2 (98%), and patients with MDR1- in group 1 (32%). The average expression of MDR1 in tumor cells in group 2 (64.0±7.0) was statistically significantly higher by 1.7 times (p = 0.003) than in group 1 (37.2±6.8) by the Mann-Whitney U-test. When distributed according to Pearson's χ2 criterion, positive MDR1 as a risk factor in the platinum-resistant group increased the risks of refractory to platinum therapy by 19 times (95% CI 2.4-148.8). Conclusions: The study demonstrated predictive significance of the MDR1 biomarker in platinum treatment in patients with ovarian cancer.
Incidence of neutropenia in breast cancer patients with administration of mecapegfilgrastim.
Authors: Peifen Fu, Yongsheng Wang, Yongqing Li, Yumin Yao, Huiping Li, Yanxia Shi, Zhiyong Yu, Lihua Song, Guifang Zhang, Zhangxia Ren, Gang Cheng, Lifang Ding, Jun Yan, Jing Zhang, Jun Bie, Chao Yuan, Zhanggui Wang, Jun Ma
Journal: Journal of Clinical Oncology (2021)

e24070 Background: Neutropenia is the frequently observed adverse events for breast cancer patients under chemotherapy. Prophylactic administration of mecapegfilgrastim could reduce the incidence of grade 3/4 neutropenia/febril neutropenia(FN). The effectiveness of mecapegfilgrastim in breast cancer patients and different subgroups were explored. Methods: Patients with breast cancer and tolerable of mecapegfilgrastim were prospectively enrolled in a real-world study. All the patients received mecapegfilgrastim prophylacticly at least in chemotherapy cycle one. The incidence of grade 3/4 neutropenia/febril neutropenia in all patients and subgroups were presented. Results: 322 eligible patients were enrolled. The median age was fifty one years. The ECOG performace score was 0 – 1. In total, 752 chemothrapy cycles were conducted. Grade 3/4 neutropenia occurred in 44 (5.9 %) cycles, grade 4 neutropenia occurred in 16 (2.1 %) cycles. FN were reported in 4 (1.2 %) patients. The incidence of grade 3/4 neutropenia were stratificated by age group (≥65, ＜65), chemotherapy history, radiotherapy history, baseline absolute white blood cell count (≥4.0 ×10 9 /L, ＜4.0 ×10 9 /L), baseline absolute neutrophil count (≥2.0 ×10 9 /L, ＜2.0 ×10 9 /L), baseline hemoglobin level (≥110 g/L, ＜110 g/L) and chemotherapy regimens (High risk of FN, intermediate risk of FN). The results showed that patients with baseline hemoglobin of ≥110 g/L and ＜110 g/L had grade 3/4 neutropenia of 5% and 14.8 % respectively (P = 0.017). Patients treated with high FN risk chemotherapy and intermediate FN risk chemotherapy had grade 3/4 neutropenia of 0.9 % and 8.9 % respectively (P = 0.003). No significant difference of incidence of grade 3/4 neutropenia between other subgroups were found. Patients treated with cyclophosphamide and epirubicin (AC, classified as intermediate risk of FN by investigator) had grade 3/4 neutropenia of 15.4 %; Patients treated with cyclophosphamide, docetaxel and epirubicin (TAC, classified as high risk of FN by investigator) had grade 3/4 neutropenia of 14.3 %; Patients treated with docetaxel monotherapy (classified as intermediate risk of FN by investigator) had grade 3/4 neutropenia of 4.9 %. Conclusions: Prophylactic administration of mecapegfilgratim reduced the incidence of grade 3/4 neutropenia/febril neutropenia. Baseline hemoglobin level and specific chemotherapy regimen could be a useful prognostic facots for neutropenic events after administered mecapegfilgrastim.
The impact of COVID-19 on clinical cancer care: An individual-patient level analysis.
Authors: Lynsey M Drewett, Sian Alexandra Pugh, Rosalind Kieran, Binu Nair, Hossameldin Attia, Muhammad Iftikhar Sabar, Isabel Milne, Sharon Saunders, Jennie Bragg, Deborah Whitehorn, Jonathan Lay, Oscar M Rueda, Fiona Harris, Sarah Joanne Welsh, Gary Doherty, Bristi Basu, Jean Abraham, Emma Beddowes, Philippa Gail Corrie, Brent O'Carrigan
Journal: Journal of Clinical Oncology (2021)

1533 Background: At the outset of the COVID-19 pandemic, concerns for the safety of patients receiving anti-cancer treatment coupled with pressures on healthcare services prompted review of standard clinical care pathways in the UK. Revised consensus treatment guidelines were generated. Individual patient-level data regarding actual treatment modifications implemented in clinical practice are lacking. Methods: All anti-cancer treatment plans of patients with breast, lung, renal, hepatopancreatobiliary, CNS cancers and melanoma attending a single academic cancer centre in the UK between 16 March and 31 May 2020 were reviewed and any modifications to standard practice were documented. The effect of patient (age, ECOG performance status [PS], sex) and cancer (site, stage, treatment intent) characteristics on likelihood of treatment modifications were analysed using univariable and multivariable models. Results: Treatment plans for 925 patients were reviewed: median patient age was 63 (range 19-97); 66% were female; 73% were PS 0-1; 45% were on a curative pathway. Overall, 47% of all patients had one or more modifications made to their treatment plans: 53% of surgeries (primarily being delayed); 41% of radiotherapy (primarily reduced fractions delivered); 39% of systemic therapy prescriptions. 96-100% of all systemic therapy modifications resulted in treatment de-escalation, excluding endocrine therapy used as a bridge to defer primary breast cancer surgery. Biological therapy was predominantly interrupted (49%), immunotherapy was mostly omitted entirely (36%), and chemotherapy varied between interruptions (39%) or omissions (31%). Relative to the likelihood of modification to chemotherapy, surgery was significantly more likely to be modified (OR 1.69 95%CI 1.20-2.38). Chemotherapy, radiotherapy, biological therapy and immunotherapy were all modified to a similar degree. Multivariate analysis identified PS ≥2 (OR 1.79, 95% CI 1.18–2.75), but not patient age, as a predictor of treatment modification. Some tumour types were less likely to undergo any modification: stage 1-3 lung (OR 0.13, 95%CI 0.04-0.37), stage 4 lung (OR 0.26 95%CI 0.24–0.60) and stage 4 renal cancer (OR 0.22 95%CI 0.09-0.52). Conclusions: This single centre analysis demonstrated almost half of cancer patients had their treatment modified, the overwhelming majority resulting in treatment de-escalation. The impact of the treatment modifications on overall cancer patient outcomes remains to be determined.
GERM-04. PRIMARY INTRACRANIAL GERM CELL TUMORS ARE MORE PREVALENT AMONG PEDIATRIC PATIENTS OF ASIAN/PACIFIC ISLANDER RACE/ETHNICITY IN THE UNITED STATES
Authors: Nayan Lamba, Bryan Iorgulescu
Journal: Neuro-Oncology (2021)

Abstract Introduction Primary intracranial germ cell tumors (GCTs) appear to be more prevalent among pediatric patients in eastern Asia than in the U.S. Herein we use cancer registry data to evaluate whether GCT prevalence differs by race/ethnicity among U.S. pediatric patients. Methods Pediatric patients (age≤14) presenting between 2004–2017 with a primary intracranial GCT were identified by ICD-O-3 histological and topographical coding from the National Cancer Database (comprising &amp;gt;70% of cancers newly-diagnosed cancers in the U.S.), and categorized by NICHD age stages. Patients’ age, sex, race/ethnicity, and overall survival, and tumor location and size were evaluated. Results 889 pediatric patients with primary intracranial GCTs were identified, which were overwhelmingly male (64.8%) and pure germinomas (64.0%). Non-germinomatous (24.5%) and mixed (11.5%) tumor types were in the minority. Overall, primary GCTs comprised 4.9% of intracranial tumors in pediatric males and 2.9% of intracranial tumors in pediatric females. Asian/Pacific Islander pediatric patients in the U.S. had a notably higher prevalence of GCTs: among Asian/Pacific Islander males, 10.6% of all brain tumors were GCTs, compared to only 4.5% in White non-Hispanic patients, 2.8% in Black non-Hispanic patients, and 6.0% in Hispanic patients. Despite the much lower prevalence of GCTs among female patients overall, this predominance also persisted for Asian/Pacific Islander females, among whom 7.5% of brain tumors were GCTs, compared to only 2.5% in White non-Hispanic patients, 2.4% in Black non-Hispanic patients, and 4.1% in Hispanic patients. Overall, 9.4% of pediatric primary intracranial GCTs occurred in patients of Asian/Pacific Islander race/ethnicity, in contrast to 4.0% of diffuse astrocytic/oligodendroglial tumors, 2.8% of other astrocytic tumors, or 4.6% of embryonal tumors. Conclusions Primary intracranial GCTs affect a substantially larger proportion of both male and female pediatric patients of Asian/Pacific Islander race/ethnicity in the United States.
Measuring the impact and sustainability of a statewide program for identifying minority and underserved clients at risk for hereditary breast and ovarian cancer (HBOC): An eight-year follow up including transitions during the COVID pandemic.
Authors: Alice S. Kerber, Sheryl G. A. Gabram, Diane Durrence, Janet Y. Shin, Nancy M. Paris, Lynn M. Durham
Journal: Journal of Clinical Oncology (2021)

e18546 Background: The Georgia Breast Cancer Genomics Program was created with 2011-2014 funding from the Centers for Disease Control and Prevention and the Georgia Department of Public Health (GDPH). In collaboration with GDPH and the Georgia Center for Oncology Research and Education (Georgia CORE), the goal of the program has been to reduce disparities among high-risk minority and underserved women. The objective of this study is to report the 8-year surveillance data for women at increased risk for HBOC in statewide public health centers. The effect of the COVID pandemic on the program and sustainability is also reported. Methods: From 11/1/2012-12/31/2020, the program provided education, outreach and collected surveillance data using an online genetics referral screening tool as recommended by USPSTF. Providers in 159 counties and health centers across Georgia were educated in cancer family history collection and appropriate referral to genetics. When an individual was found to be at high risk, she was referred to the Georgia CORE Genetics Advanced Practice Nurse for additional education, genetic testing and follow-up. Results: Online screenings attributable to GDPH totaled 29,087 with 1,656 positive screens. 28 % of clients were less than 25 years of age and 56 % ranged from 25-54. Race: 33 % white, 41 % black, 15 % Hispanic and 11 % other or N/A. 92 % of referrals were uninsured. Genetic testing was started or completed on 430 clients. 36 individuals declined testing after counseling (reconsideration, insurance, unknown reasons) and were provided with contact information. 47 (11%) pathogenic, clinically significant mutations were identified including 37 (79 %) HBOC related mutations and 10 (21 %) Lynch related mutations. Variants of uncertain significance were identified in 90 (21 %) clients, with multiple variants in 40 of those. 27 clients have been served through GDPH for physician consultation and surveillance. 13 were referred to area resources: one diagnosed with cancer, and 7 chose referral to other health care providers. Because of the pandemic, the program transitioned to telecommunications and remote access to testing in 5/2020. From 5/2020-12/2020, 34 clients completed testing (41% minority, all uninsured). 10 (29%) clinically significant mutations were identified and heightened surveillance initiated. Conclusions: The GDPH and Georgia CORE collaborative genomics program has served clients over the past 8 years, adjusting to changing resources while reaching a significant number of minority and underserved women. The program successfully converted to remote services during the COVID pandemic. Lessons learned from this transition have been incorporated into planning for future program sustainability.
Randomized double-blind, placebo-controlled study of topical diclofenac in prevention of hand-foot syndrome in patients receiving capecitabine.
Authors: Atul Batra, Akhil P. Santosh, Raja Pramanik, Ajay Gogia, R. M. Pandey, akash kumar, Atul Sharma
Journal: Journal of Clinical Oncology (2021)

TPS12135 Background: The pathophysiology of capecitabine induced hand-foot syndrome (HFS) includes activation of cyclooxygenase (COX)-2, leading to an upregulation of the inflammatory cascade. Prophylaxis with oral celecoxib was previously reported to be associated with a significantly lower frequency of HFS (grade 1 [29.0% vs. 72.0%, p &lt; 0.001] and grade 2 [11.8% vs. 30.0%, p=0.024]) (1). The findings were confirmed in a phase III trial (2). However, the associated systemic adverse events limit routine prophylactic use. Till date, no clinical trials have assessed the role of topical non-steroidal anti-inflammatory drugs (NSAIDs) in preventing HFS. Methods: In this investigator-initiated randomised phase III double-blind, placebo controlled, parallel group trial, a total of 264 patients with any stage breast or gastrointestinal cancer planned to receive capecitabine as a single agent or in combination with other chemotherapy will be randomised (1:1) to 1% topical diclofenac or placebo (base for 1% topical diclofenac) arm at a single tertiary care cancer centre in India. Randomization will be done by stratified (male vs female, and capecitabine mono therapy vs combination) permuted block method using a computer generated random sequence and allocation concealment will be done by using sealed opaque envelopes. In both the arms, patients will be asked to apply 1 fingertip unit (FTU) of topical medication on both surfaces of bilateral hands twice daily for a total duration of 12 weeks or till development of grade 2 or higher HFS, whichever is earlier. The primary objective is to compare the effect of topical diclofenac with placebo in preventing clinically significant HFS (incidence of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 2 or higher HFS). The secondary objectives include comparison of topical diclofenac with placebo on (i) incidence of NCI CTCv5.0 all grade HFS, (ii) time to develop grade ≥2 HFS from start of capecitabine, (iii) patient-reported outcomes using HFS-14 questionnaire (iv) adherence with topical application using self-reported adherence diary, (v) capecitabine dose reductions, delays and cessation due to HFS and (vi) safety profile (NCICTCv5.0). The tertiary correlative endpoint is to correlate the occurrence and severity of HFS with serum COX-2 levels and polymorphism of dihydropyrimidine dehydrogenase (DPPD) enzyme. The trial is registered at the Clinical Trial Registry of India (CTRI/2021/01/030592). Till date, we have enrolled 12/264 patients. (1) Zhang RX et al. J Cancer Res Clin Oncol. 2011;137(6):953-957. (2) Zhang RX et al. Annals of oncology. 2012;23(5):1348-1353. Clinical trial information: CTRI/2021/01/030592.