tbuckley/cabot-search huggingface dataset:
Trainings needs of allied health professionals caring for sexual and gender minority adolescents and young adults with cancer: A qualitative analysis.
Authors: Ash B. Alpert, Vikas Gampa, Susan Thomas Vadaparampil, Gwendolyn P. Quinn
Journal: Journal of Clinical Oncology (2021)

e18532 Background: Little is known about the training needs of allied health professionals who provide reproductive health counseling and other support services to sexual and gender minority (SGM) adolescent and young adult (AYA) people with cancer. Methods: A 28-item electronic survey with 4 qualitative items was distributed to 601 allied health professionals who had participated in a training focused on reproductive health needs in AYA people with cancer. Open-ended questions invited respondents to describe personal experiences, reservations, and suggestions for improving SGM AYA cancer care. Using an interpretive description methodology, two investigators independently analyzed qualitative survey responses noting thematic saturation. Together, they refined themes, resolving disagreements with consensus. Interrater reliability was 88%. Results: 321 people participated in the survey and 190 answered open-ended questions. Themes included: 1) an ecosystem exists around patients’ interactions with clinicians and institutions; 2) institutional and individual assumptions result in stigmatization of SGM AYA people with cancer; 3) accommodating patients and providing clinicians with relevant education and experiences are initial steps to decrease stigma; and 4) improving the care for SGM AYA people with cancer may require transformative approaches that incorporate intersectional frameworks and challenge current systems. Conclusions: Improving the quality of care for SGM AYA people with cancer will require systemic and institutional change as well as educational interventions.
RETRACTED ARTICLE: Trans-silencing effect of the 3′RR immunoglobulin heavy chain enhancer on Igκ transcription at the pro-B cell stage
Authors: Nour Ghazzaui, Hussein Issaoui, Ophélie Alyssa Martin, Alexis Saintamand, Jeanne Cook-Moreau, Yves Denizot, François Boyer
Journal: Cellular and Molecular Immunology (2018)
The role of <i>HPSE</i> in <i>BRAF</i> V600E-mutant colorectal cancer.
Authors: Mengling Liu, Xiaojing Xu, Ke Peng, Pengcong Hou, Qing Liu, Yiyi Yu, Tianshu Liu
Journal: Journal of Clinical Oncology (2021)

3530 Background: BRAF mutations occur in about 10% of colorectal cancer (CRC), more than 90% of which are BRAF V600E mutation. Patients (pts) with BRAF V600E mutation present poor prognosis. Complex molecular biological mechanisms in this population have not been well annotated. HPSE plays a multifunctional role in cell proliferation, invasion and angiogenesis in cancer. Here we identified differentially expressed genes (DEGs) between pts with and without BRAF V600E mutation, and then focused on the function of HPSE, one of top DEGs, in BRAF V600E-mutant CRC. Methods: Clinical and transcriptional data of pts with CRC from The Cancer Genome Atlas (TCGA, n = 525) database and GSE39582 dataset (n = 510) were analyzed to explore the top overlapped DEGs between BRAF V600E mutant and wild-type pts. Records and tumor samples of 172 pts with BRAF V600E-mutant CRC diagnosed at Zhongshan Hospital Fudan University between 6/2015-12/2018 were collected. The HPSE protein expression status of tumor samples was evaluated by immunohistochemistry staining. Moderate or strong staining in &gt; 25% of tumor cells was interpreted as HPSE positive. Overall survival (OS) was analyzed using Kaplan-Meier Curves with Log-rank test and multivariable Cox regression. Next, lentiviral shRNA-based silencing of HPSE was performed in two BRAF V600E-mutant CRC cell lines (HT-29, RKO). The effect of HPSE on tumor growth was investigated through colony formation assays, cell cycle assays and subcutaneous xenograft models. Results: The top overlapped genes of the DEGs list included HPSE, TFF2, AXIN2, MLH1, RNF43, EPM2AIP1. Among them, HPSE had significantly high expression in BRAF V600E-mutant group. Of 172 pts with BRAF V600E mutation, 83 were identified as HPSE positive and 89 were negative. Two groups were generally well balanced on age (p = 0.096), gender (p = 1.000), location (p = 0.658), stage (p = 0.249) and MMR status (p = 0.129). HPSE positive pts had a significantly worse OS in comparison to HPSE negative pts (p = 0.037, median OS not reached). The multivariate analysis showed that HPSE positive was independently associated with inferior OS [HR 1.97 (95%CI: 1.02 – 3.80), p = 0.044). Silencing HPSE gene impaired colony formation activity significantly and arrested more cells in G0/G1 phase of BRAF V600E-mutant CRC cell lines. Tumor growth was inhibited apparently in HPSE-silencing xenograft models. Conclusions: Pts with BRAF V600E-mutant CRC had a high HPSE expression level, while HPSE protein expression was an independent prognostic factor for this population. The silencing of HPSE expression in BRAF V600E-mutant CRC cell lines inhibited cell proliferation and tumor growth in vitro and in vivo. HPSE may contribute to the poor prognosis of BRAF V600E-mutant CRC and might be a promising therapeutic target for this subtype of CRC.
MONEO: A phase II study of avelumab (Av) plus FLOT in the peri-operative treatment for patients (pts) with resectable gastric or gastroesophageal junction cancer (GC).
Authors: MARIA ALSINA, Mariano Ponz-Sarvise, Dario Lopez Garcia, Marta Gonzalez, Carlos E De Andrea, Alena Gros, Ana Vivancos, Paula Jiménez-Fonseca, Marc Diez Garcia, Virginia Arrazubi, Enrique Sanz-Garcia, Eva Martínez de Castro, Raquel Guardeno, Mariona Calvo, Cristina Buges, Federico Longo, Josep Tabernero, Guillermo Villacampa, Susana Muñoz, Ignacio Melero
Journal: Journal of Clinical Oncology (2021)

TPS4155 Background: GC represents a worldwide problem; radical surgery remaining the gold standard of curative treatment. In the West, even with peri-operative chemotherapy, 5-year survival rate is approximately 40%. GC is a heterogeneous disease, well characterized by different molecular classifications, all having in common the role of the immune system and a T-cell inflamed phenotype across all subtypes. The anti-PD-L1 Av antibody has demonstrated efficacy in GC with response rates of around 10% in the refractory setting. The addition of other immune checkpoint inhibitors to chemotherapy have demonstrated efficacy in the metastatic setting. The combination of Av to perioperative chemotherapy may increase pathological responses by a synergistic effect, and then improving the survival (OS). Methods: The MONEO is an open-label, non-randomized, multicentric, phase II study that explores the combination of Av plus peri-operative FLOT (docetaxel, oxaliplatin, fluorouracil/leucovorin) in resectable GC pts. EudraCT 2019-000782-21; ClinicalTrials NCT03979131. Main inclusion criteria require pts with histologically proven GC, stage Ib (T1N1 only) - IIIC (7th AJCC Ed), available paraffin block from diagnosis and surgery, evaluable disease (RECIST 1.1) amenable to radical surgery. Significant comorbidities and active autoimmune diseases are excluded. Treatment consists of surgery with 4 peri-operatory cycles of FLOT + Av, followed by Av up to one year. The primary objective is the pathological complete response (pCR) rate, compared to historical data. Secondary objectives include OS, disease-free survival, R0 resection rate, tolerability and biomarker analysis. Key point is the comprehensive biomarker analysis from tissue and blood samples (pathological immune response, TCR clonality, immune contexture characterization, immunodynamic monitoring). Statistics for an estimated 33% pCR (historical 16%), 82% power, 0.1 one-side type I error. 37 pts will be recruited from 10 Spanish centers. The sponsor is Vall d'Hebron Institute of Oncology (VHIO), principal investigators Dr. Melero and Dr. Alsina. In compliance with the Helsinki Declaration. At a data cut-off day of 5 th of February 2021, 38 patients have been enrolled, 27 of them have had the surgery. Although the difficulties during the COVID19 pandemia, only two patients had been withdrawn from the study. Clinical trial information: NCT03979131.
Expression of end-binding protein 1 (EB1), a potential response-predictive biomarker for lisavanbulin, in glioblastoma and various other solid tumor types.
Authors: Magdalena Skowronska, Crescens Diane Tiu, Alexandar Tzankov, Fatima König, Joanne Lewis, Igor Vivanco, Malte Kleinschmidt, Kirk Beebe, Stephanie Anderson, Felix Bachmann, Marc Engelhardt, Heidi A Lane, Thomas Kaindl, Alexandru C Stan, Elizabeth Ruth Plummer, T.R. Jeffry Evans, Inti Zlobec, Juanita Suzanne Lopez
Journal: Journal of Clinical Oncology (2021)

3118 Background: EB1, a protein located on the plus-ends of microtubules is involved in microtubule function and has been associated with glioblastoma (GBM) stem-cell-ness and more aggressive disease. Lisavanbulin (BAL101553) is a prodrug of the lipophilic small molecule BAL27862, that promotes tumor cell death by modulating the spindle assembly checkpoint and has been shown in rodents to efficiently penetrate the brain. Data from GBM mouse models and recent phase 1 clinical data (Lopez et al. ESMO 2020) suggest that EB1 is a response-predictive marker for lisavanbulin in GBM. A phase 2 study is ongoing to confirm this hypothesis (NCT02490800). A proof-of-concept in GBM would support an expansion of EB1-directed lisavanbulin clinical development in non-GBM tumors, which requires prevalence estimates of EB1-positivity in non-GBM tumor types. Methods: Tissue samples from GBM and other tumor types were stained for EB1 using a CE-marked immunohistochemistry Clinical Trial Assay (Targos Molecular Pathology GmbH, Kassel Germany). EB1-positivity was assessed by a board-certified pathologist based on the percentage of tumor cells showing moderate or strong staining for EB1, using thresholds of ≥50%, ≥60% and ≥70% of tumor cells with EB1 positivity. Whole transcriptome sequencing (WTS) using RNAseq was performed in a subset of tissue samples to develop a potential RNA-based predictive response signature for lisavanbulin. Results: 73 GBM tissue samples and 333 tissue samples from 13 other cancer types were stained for EB1. The strongest overall signal for EB1-positivity was obtained for medulloblastoma, neuroblastoma and GBM. In addition, moderate or strong EB1-staining in ≥50% of tumor cells was observed in samples from colorectal cancer (CRC), non small-cell lung cancer (NSCLC), metastatic melanoma, small-cell lung cancer (SCLC) and triple-negative breast cancer (TNBC). An expanded staining campaign is ongoing in these cancer types. Initial results from the ongoing WTS analyses show marked differences in gene expression profiles between EB1-positive and -negative cases. Conclusions: Strong EB1-positivity is infrequent but occurs in a variety of tumor types, with the strongest signals in medulloblastoma, neuroblastoma and GBM. A phase 2 study is ongoing to assess prospectively whether EB1 is a response-predictive biomarker for lisavanbulin in GBM.[Table: see text]
Efficacy of Wolbachia-Infected Mosquito Deployments for the Control of Dengue
Authors: Adi Utarini, Citra Indriani, Riris A. Ahmad, Warsito Tantowijoyo, Eggi Arguni, M. Ridwan Ansari, Endah Supriyati, D. Satria Wardana, Yeti Meitika, Inggrid Ernesia, Indah Nurhayati, Equatori Prabowo, Bekti Andari, Benjamin R. Green, Lauren Hodgson, Zoe Cutcher, Edwige Rancès, Peter A. Ryan, Scott L. O’Neill, Suzanne M. Dufault, Stephanie K. Tanamas, Nicholas P. Jewell, Katherine L. Anders, Cameron P. Simmons
Journal: New England Journal of Medicine (2021)

Aedes aegypti mosquitoes infected with the wMel strain of Wolbachia pipientis are less susceptible than wild-type A. aegypti to dengue virus infection.We conducted a cluster-randomized trial involving releases of wMel-infected A. aegypti mosquitoes for the control of dengue in Yogyakarta, Indonesia. We randomly assigned 12 geographic clusters to receive deployments of wMel-infected A. aegypti (intervention clusters) and 12 clusters to receive no deployments (control clusters). All clusters practiced local mosquito-control measures as usual. A test-negative design was used to assess the efficacy of the intervention. Patients with acute undifferentiated fever who presented to local primary care clinics and were 3 to 45 years of age were recruited. Laboratory testing was used to identify participants who had virologically confirmed dengue (VCD) and those who were test-negative controls. The primary end point was symptomatic VCD of any severity caused by any dengue virus serotype.After successful introgression of wMel into the intervention clusters, 8144 participants were enrolled; 3721 lived in intervention clusters, and 4423 lived in control clusters. In the intention-to-treat analysis, VCD occurred in 67 of 2905 participants (2.3%) in the intervention clusters and in 318 of 3401 (9.4%) in the control clusters (aggregate odds ratio for VCD, 0.23; 95% confidence interval [CI], 0.15 to 0.35; P = 0.004). The protective efficacy of the intervention was 77.1% (95% CI, 65.3 to 84.9) and was similar against the four dengue virus serotypes. The incidence of hospitalization for VCD was lower among participants who lived in intervention clusters (13 of 2905 participants [0.4%]) than among those who lived in control clusters (102 of 3401 [3.0%]) (protective efficacy, 86.2%; 95% CI, 66.2 to 94.3).Introgression of wMel into A. aegypti populations was effective in reducing the incidence of symptomatic dengue and resulted in fewer hospitalizations for dengue among the participants. (Funded by the Tahija Foundation and others; AWED ClinicalTrials.gov number, NCT03055585; Indonesia Registry number, INA-A7OB6TW.).
Interim PSMA PET/CT for response evaluation during LuPSMA treatment in mCRPC (INTERIM PET): An explorative, multicenter study.
Authors: Andrei Gafita, Isabel Rauscher, Manuel Weber, Boris A. Hadaschik, Hui Wang, Wesley R Armstrong, Robert Tauber, Johannes Czernin, Matthew Rettig, Ken Herrmann, Jeremie Calais, Wolfgang A Weber, Matthias R. Benz, Wolfgang Peter Fendler, Matthias Eiber
Journal: Journal of Clinical Oncology (2021)

5066 Background: The aim of this analysis was to evaluate the prognostic value of interim PSMA PET/CT in men with metastatic castration-resistant prostate cancer (mCRPC) treated with 177 Lu-PSMA and to develop a novel framework for Response Evaluation Criteria In PSMA-imaging (RECIP). Methods: This was an explorative, multicenter, retrospective study; 124 men with mCRPC who underwent 177 Lu-PSMA treatment and received PSMA-PET/CT at baseline (bPET) and at interim after two cycles of treatment (iPET) met the eligibility criteria and were included in this analysis. The primary endpoint was overall survival (OS). Pairs of bPET and iPET were interpreted by three independent readers for appearance of new lesions. Whole-body tumor lesions were segmented using qPSMA software and total PSMA-positive tumor volume (PSMA-VOL) was obtained. Changes in PSMA-VOL on iPET relative to bPET were calculated. After being tested separately for associations with OS, appearance of new lesions and changes in PSMA-VOL were combined to develop RECIP. Results: The median OS was 13.5 months (95%CI, 11.6-15.4). Appearance of at least one new lesion on iPET was observed in 73 (59%) patients and was associated with poor OS (hazard ratio [HR] 2.23; 95%CI, 1.51-3.28; P &lt;.001). Based on the current data, RECIP were defined as: partial response (PSMA-PR) as a decline ≥20% in PSMA-VOL and no appearance of new lesions; progressive disease (PSMA-PD) as an increase ≥20% in PSMA-VOL and appearance of new lesions; stable disease (PSMA-SD) was defined as any condition but not PSMA-PR or PSMA-PD. The OS of men with PSMA-PD (n = 41) was significantly worse compared to men with PSMA-SD (n = 47; HR 2.52; 95%CI, 1.61–3.93; P &lt;.001) and PSMA-PR (n = 36; HR 4.16; 95%CI, 2.54–6.78; P &lt;.001). PSMA-SD was associated with significantly worse OS compared to PSMA-PR (HR 1.65; 95%CI, 1.02–2.65; P =.039). The time dependent C-index of associations with OS for response according to RECIP was 0.68 (95%CI, 0.63-0.72). Conclusions: Interim staging using PSMA-PET/CT and response classification by RECIP is prognostic for survival of men with mCRPC treated with 177 Lu-PSMA. Validation of these findings in clinical trials is warranted.
Real-world outcomes in older adults treated with immunotherapy: A United Kingdom multicenter series of 2,049 patients.
Authors: Anna Claire Olsson-Brown, Mark Baxter, Caroline Dobeson, Laura Feeney, Rebecca Lee, Alec Maynard, Shagufta Mirza, Shefali Parikh, Lisa Jane Rodgers, Abdulazeez Salawu, Rohan Shotton, Nadina Tinsley, Jonathan Heseltine, Jenny Cotton, Daniel Hughes, Steven Zhao, James Parry, Christopher Jones, Michael Rowe, Ann Tivey
Journal: Journal of Clinical Oncology (2021)

12026 Background: Immune checkpoint inhibitor (ICI) therapy is now commonly used in a range of tumours and settings. Most data relating to outcomes and rates of immune-related adverse events (irAE) is derived from clinical trial or registry populations and small case series. Limited data exist for patients aged &gt; 75 years. Here we present a multi-centre, real-world analysis of the outcomes and incidence of irAEs in older adults managed within a single comprehensive public health service. We also compare these outcomes to younger patients in the same cohort. Methods: A retrospective analysis of 2049 patients treated with ICIs was undertaken across 12 centres. All patients were managed within the UK National Health Service outside of a trial setting between June 2016 and September 2018. Patients received either ICI monotherapy (MT) or duel combination ICI therapy (CT) for malignant melanoma (MM), non-small cell lung cancer (NSCLC) or renal cell cancer (RCC). Data were collected using a standardised, collection tool. IrAEs ≥ grade 2 or all-grade endocrinopathies were recorded as per the Common Terminology Criteria for Adverse Events (V5) (CTCAE). Statistical analyses were performed using T-tests, Mann-Whitney and Chi-squared. Kaplan-Meier analysis and log-rank test were used for overall survival (OS) analysis. Results: 409 (20%) of patients were aged &gt; 75 years(a), 1413 (69%) aged 50-75(b) and 227 (11.1%) aged &lt; 50(c). There was no difference in sex, ethnicity or PD-L1 status (in the NSCLC cohort) between groups. Older patients were less likely to receive combination therapy (3%(a) v 13%(b) v 34%(c), p &lt; 0.001). There was no difference in median OS across age groups in the cohort as a whole (p = 0.822) or for the individual tumour groups when treated with single agent ICI. Across the total cohort patients aged &gt; 75 had no increased risk of any irAE (35%(a) v 33%(b) v 41%(c),p = 0.074). However there was an increase in irAEs in older patients treated with MT (36%(a) v 26(b) v 25%(c), p = 0.011) However there was no difference in the &gt; 75s with regard to severe (G3/4) toxicity, toxicity type, admission or discontinuation due to toxicity in the aPD-1 group. In the overall cohort younger patients were more likely to develop irAEs and be admitted. Conclusions: Patients aged &gt; 75 years treated with anti-PD1 therapy in the standard of care setting derive similar survival benefit to younger patients. There was no increase in ≥G3 toxicity. Our data support the safety of single agent aPD-1 ICI therapy in older adults and provide reassurance relating to the impact of toxicity.[Table: see text]
Characterizing the United Kingdom Congenital Thrombotic Thrombocytopenic Purpura Population
Authors: Ferras Alwan, Chiara Vendramin, Ri Liesner, Tina Dutt, Amanda Clark, Jayashree Motwani, Will Lester, Vickie McDonald, Rachel Rayment, Nichola Cooper, Richard Gooding, Hamish Lyall, Tina Biss, Joost van Veen, Henry G Watson, John-Paul Westwood, Mari Thomas, Marie Scully
Journal: Blood (2017)
PALOMAGE, a French real-world cohort of elderly women beyond age 70 with advanced breast cancer receiving palbociclib: Baseline characteristics and safety evaluation.
Authors: Philippe Caillet, Marina Pulido, Etienne Brain, Claire Falandry, Isabelle Desmoulins, Djamel Ghebriou, Pierre-Louis Soubeyran, Elena Paillaud, Nada Rifi, Jean Michel Vauthier, Louis Tassy, Elisabeth Carola
Journal: Journal of Clinical Oncology (2021)

1012 Background: Advanced breast cancer (ABC) is common in older patients, resulting from the high incidence of breast cancer beyond age 70. This population is often limited in clinical trials. Endocrine therapy (ET) combined with a CDK4/6 inhibitor is the standard of care in ABC overexpressing hormonal receptors (HR+). Data specific to older patients are scarce in the literature, deserving further research. Methods: PALOMAGE is an ongoing French prospective study evaluating palbociclib (PAL) + ET in real life setting in women aged ≥70 with HR+ HER2- ABC, split in 2 cohorts: ET sensitive patients with no prior systemic treatment for ABC (cohort A), and ET resistant patients and/or with prior systemic treatment for ABC (cohort B). Data collected include clinical characteristics, quality of life (EORTC QLQ-C30 and ELD14) and geriatric description [G8 and Geriatric-COre DatasEt (G-CODE)]. This analysis reports on baseline characteristics and safety data for the whole population. Results: From 10/2018 to 10/2020, 400 and 407 patients were included in cohort A and B, respectively. The median age was 79 years (69-98), 15.1% with an age &gt; 85. ECOG performance status (PS) was ≥2 in 17.9% patients, 68.3% had a G8 score ≤14 suggesting frailty, 32.1% had bone only metastasis, and 44% had visceral disease. 35.8% of patients in cohort B had no prior treatment for ABC. Safety data were available for 787 patients. The median follow-up was 6.7 months (IC95% = 6.1-7.6). At start of treatment, full dose of PAL (125 mg) was used in 76% of the patients: 62.6%, 68.7% and 71.6% of patients aged ≥ 80, those with ECOG PS ≥2 and those with a G8 score ≤14, respectively. In the safety population, 70% had ≥1 adverse event (AE), including 43.1% grade 3/4 AE, and 22.9% ≥ 1 serious AE. Most frequent AE reported were neutropenia (43.2%), anemia (17.5%), asthenia (16.3%) and thrombocytopenia (13.6%). Grade 3/4 neutropenia was observed in 32.3% of patients, with febrile neutropenia in 1.1%. Grade 3/4 AE PAL-related were reported in 40.1%, 31.4% of patients aged &lt; 80, ≥80, respectively. Regarding PAL, 23.4% of patients had a dose reduction and 41.8% had a temporary or permanent discontinuation due to AE. Safety data were similar in both cohorts. Geriatric data and impact on safety will be presented. Conclusions: PALOMAGE is a unique large real-world cohort focusing on older patients treated with PAL in France. These preliminary data do not suggest any new safety signal, matching data derived from PALOMA trials. The occurrence of less grade3/4 AE related to PAL in patients aged 80 and beyond might reflect the 30% decrease of PAL dose upfront. Effectiveness analyses are eagerly awaited. Clinical trial information: EUPAS23012 .