tbuckley/cabot-search huggingface dataset:
The mechanism of the growth inhibitory effect of paclitaxel on gefitinib-resistant non-small cell lung cancer (NSCLC) cells during the COVID-19 pandemic.
Authors: Md Mohiuddin, Hideharu Kimura, Satoshi Watanabe, Miki Abo, Takashi Sone, Keigo Saeki, Nanao Terada, Kota Tanimura, Kazuo Kasahara
Journal: Journal of Clinical Oncology (2021)

e15007 Background: Coronavirus disease 2019 (COVID-19) poses a great challenge for the treatment of cancer patients. It presents as a severe respiratory infection in aging individuals, including lung cancer patients. COVID-19 may be linked to the progression of aggressive lung cancer. In addition, the side effects of chemotherapy, such as chemotherapy resistance and the acceleration of cellular senescence, can worsen COVID-19. Given this situation, we investigated the role of paclitaxel (a chemotherapy drug) in the cell proliferation, apoptosis, and cellular senescence of gefitinib-resistant non-small-cell lung cancer (NSCLC) cells (PC9-MET) to clarify the underlying mechanisms. Methods: PC9-MET cells were treated with paclitaxel for 72 h and then evaluated by a cell viability assay, DAPI staining, Giemsa staining, apoptosis assay, a reactive oxygen species (ROS) assay, SA-β-Gal staining, a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and Western blotting. Results: Our results revealed that paclitaxel significantly reduced the viability of PC9-MET cells and induced morphological signs of apoptosis. The apoptotic effects of paclitaxel were observed by increased levels of cleaved caspase-3 (Asp 175), cleaved caspase-9 (Asp 330) and cleaved PARP (Asp 214). In addition, paclitaxel increased ROS production, leading to DNA damage. Inhibition of ROS production by N-acetylcysteine attenuates paclitaxel-induced DNA damage. Importantly, paclitaxel eliminated cellular senescence, as observed by SA-β-Gal staining. Cellular senescence elimination was associated with p53/p21 and p16/pRb signaling inactivation. Conclusions: Given these findings, paclitaxel may be a promising anticancer drug and offer a new therapeutic strategy for managing gefitinib-resistant NSCLC during the COVID-19 pandemic.
Relevance of Platinum-free Interval and <i>BRCA</i> Reversion Mutations for Veliparib Monotherapy after Progression on Carboplatin/Paclitaxel for g<i>BRCA</i> Advanced Breast Cancer (BROCADE3 Crossover)
Authors: Shannon L. Puhalla, Véronique Diéras, Banu K. Arun, Bella Kaufman, Hans Wildiers, Hyo S. Han, Jean-Pierre Ayoub, Vered Stearns, Yuan Yuan, Teresa Helsten, Bridget Riley-Gillis, Erin Murphy, Madan G. Kundu, Meijing Wu, David Maag, Christine K. Ratajczak, Cyril Y. Ramathal, Michael Friedlander
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Safety, efficacy, and exploratory biomarker analyses were evaluated in patients with advanced HER2-negative germline breast cancer susceptibility gene (gBRCA)-associated breast cancer enrolled in the BROCADE3 trial who received crossover veliparib monotherapy after disease progression on placebo plus carboplatin/paclitaxel. Patients and Methods: Eligible patients (N = 513) were randomized 2:1 to veliparib plus carboplatin/paclitaxel or placebo plus carboplatin/paclitaxel; patients had variable platinum-free intervals (PFI) at progression. In the placebo arm, patients were eligible to receive crossover veliparib monotherapy (300–400 mg twice daily continuous). Antitumor activity and adverse events were assessed during crossover veliparib treatment. BRCA reversion mutations at crossover were analyzed retrospectively using next-generation sequencing on plasma circulating tumor DNA (ctDNA). Results: Seventy-five patients in the placebo plus carboplatin/paclitaxel arm received ≥1 dose of crossover veliparib postprogression (mean treatment duration: 154 days). Eight of 50 (16%) patients with measurable disease had a RECIST v1.1 response. Activity was greater in patients with PFI ≥180 days compared with &amp;lt;180 days [responses in 23.1% (3/13) vs. 13.5% (5/37) of patients]. BRCA reversion mutations that restored protein function were detected in ctDNA from 4 of 28 patients tested, and the mean duration of crossover veliparib monotherapy was &amp;lt;1 month in these 4 patients versus 7.49 months in patients lacking reversion mutations. The most frequent adverse events were nausea (61%), vomiting (29%), and fatigue (24%). Conclusions: Crossover veliparib monotherapy demonstrated limited antitumor activity in patients who experienced disease progression on placebo plus carboplatin/paclitaxel. PFI appeared to affect veliparib activity. BRCA reversion mutations may promote cross-resistance and limit veliparib activity following progression on platinum.
Clinical Outcomes of Different Regimens in Patients Newly Diagnosed with Acute Promyelocytic Leukemia
Authors: Rui Qin, Xiaofan Li, Nainong Li, Meijuan Huang, Zheng Jing, Fenge Yang, Yuanzhong Chen, Jianda Hu, Rong Zhan, Shaoyuan Wang, Zhizhe Chen, Jianzhen Shen, Danhui Fu, Yanjuan Lin, Tingbo Liu
Journal: Blood (2017)
Pediatric cancer communication in Guatemala.
Authors: Dylan E. Graetz, Silvia Elena Rivas, Huiqi Wang, Yuvanesh Vedaraju, Meenakshi Devidas, Ana Lucia Fuentes, Annie Caceres-Serrano, Federico Antillon-Klussmann, Monika Metzger, Carlos Rodriguez-Galindo, Jennifer W. Mack
Journal: Journal of Clinical Oncology (2021)

e18508 Background: Effective diagnostic communication is a cornerstone of cancer care. While &gt; 90% of children with cancer live in low- and middle-income countries, little is known about patients’ and families’ communication priorities and experiences. We examined parent priorities for communication and the quality of information-exchange and decision-making during diagnostic communication in Guatemala. Methods: This study was conducted at Unidad Nacional de Oncologia Pediatrica. A cross-sectional survey was verbally administered in Spanish to 100 parents of children with cancer within 8 weeks of diagnosis. The survey included items utilized in pediatric communication studies from high-income countries and novel questions developed specifically for the study population. Results: Guatemalan parents prioritized communication functions including information exchange (99%), fostering healing relationships (98%), decision-making (97%), enabling self-management (96%) and managing uncertainty (94%) over functions such as responding to emotions (66%) and cultural awareness (48%). Almost all Guatemalan parents (96%) wanted as many details as possible about their child’s cancer. However, only 67% reported that they were always given the information they needed without asking for it, and most said they sometimes (56%) or always (18%) had questions they wanted to discuss with the doctor but did not. Half of parents (54%) correctly identified their child’s diagnosis, primary site, extent of disease (localized versus metastatic), length of proposed treatment, and treatment intent (curative versus palliative). Parents of children diagnosed with leukemia were more likely to understand all pieces of information than those whose children had solid tumors (p &lt; 0.001). Most parents (76%) preferred to share in decision-making with oncologists. Two-thirds of parents (65%) held their preferred role in decision-making, with fathers more likely to hold their preferred role than mothers (p = 0.02). Reflecting on decisions they had made, 94% of parents strongly agreed they had made the right decisions. However, 17% of parents endorsed feeling that their choices had caused their children harm. Conclusions: Similar to findings from the United States, parents in Guatemala prioritize many aspects of diagnostic communication, especially information exchange, development of healing relationships, and decision-making. Nonetheless, many parents report challenges in information exchange and decision-making, suggesting a need for interventions to support communication processes.
Evaluating the dyadic management of sexuality-related parameters in women with early breast cancer (EBC): The emergence of “partner reported outcome measurements” (pROMs).
Authors: Eli Sapir, Benjamin W. Corn, Lior Hasid, Irad Deutsch, Daniel A. Vorobiof
Journal: Journal of Clinical Oncology (2021)

e24118 Background: Patient-centered healthcare has focused on incorporating the values of patients (Pts) during clinical decision-making. Accordingly, assessments are often executed with patient reported outcome measurements (PROMs). In the context of tumors located in a sexual organ, life quality may be predicated on the perception of the patient’s partner when such a relational dyad exists. Therefore, we created a “partner” reported outcome measurements (pROMs). Accordingly, we sought to query the interconnection of PROMs and pROMs in the setting of early breast cancer (EBC) by using a digital health technology application. Methods: In this ongoing study, 93 EBC Pts and 18 partners, active members of Belong.life, a social engagement platform for cancer Pts and caregivers, replied anonymously and voluntarily to a targeted survey related to sexuality and intimacy parameters in the Pts and their partners. 72% of the partners were 50-69 years of age (yoa), 61% were Caucasian. 70% of the Pts were 50-69 yoa and 72% Caucasian. 72% of the Pts and 78% of the partners had college and university degrees. At diagnosis 78% of the Pts had Stages 1-2, 44% had breast conserving surgery, and most (78%) received chemotherapy. Results: We report the interim results of the first 14 patients-partner dyads. At the time of diagnosis, 86% of partners and 50% of Pts were very or extremely concerned about the patient’s health. Of note, 43% of Pts were not concerned at all or slightly concerned about their own health. With the passage of time, the concern about the patient’s health had decreased to 50% among the partners and 28% among the Pts. Regarding intimacy and sexuality issues prior to the EBC diagnosis, 64% of the Pts didn’t have any complaints but it changed dramatically after diagnosis with 50% mentioning less sex drive and 40% less intimacy. In the partners group 67% didn’t have complaints before the diagnosis but 28% voiced complaints after the diagnosis. Only half of Pts and partners felt they could speak freely about their mutual feelings. Only 23% of Pts and 11% of partners indicated they would agree to seek professional help for issues related to sexuality and intimacy. Ultimately, 71% of Pts and 79% of partners felt happy with each other. Conclusions: Partners were very concerned about the health of Pts; however, the dyad was not always synchronized. Notwithstanding it, the dyad adjusted their concerns during the course of treatment. Body changes had modest effect on the relationship. While dissatisfaction of sexual activity was evident it did not significantly affect the feelings of patients and partners towards each other. The development of pROMs could re-synchronize the dyad thereby creating a more meaningful cancer journey.
Distinct immune trajectories in patients with chromosome 22q11.2 deletion syndrome and immune-mediated diseases
Authors: T Blaine Crowley, Ian M Campbell, Emily J Liebling, Michele P Lambert, Lorraine E Levitt Katz, Jennifer Heimall, Alice Bailey, Daniel E McGinn, Donna M McDonald McGinn, Kathleen E Sullivan
Journal: Journal of Allergy and Clinical Immunology (2021)
A phase II study of short course FOLFOX chemotherapy with either nivolumab (Nivo) or Nivo plus radiation in the first line treatment of metastatic or unresectable gastroesophageal (GEA) cancers.
Authors: Rutika Mehta, Sarbajit Mukherjee, Kelsey Klute, Haeseong Park, Uqba Khan, Sahrish Khan, Carina Puello, Sabrina Machado, Paul J. Christos, Nicholas J. Sanfilippo, Manish A. Shah
Journal: Journal of Clinical Oncology (2021)

TPS4157 Background: GEA remains incurable and novel therapies are needed. Studies have shown that cytotoxic chemotherapy can enhance antigenicity of tumors, leading to the recent practice changing studies that demonstrate checkpoint inhibition therapy combined with chemotherapy in PD-L1 overexpressing patients significantly improves patient survival (Keynote-590 and Checkmate-649). But long-term use can also subsequently dampen the immune response. Moreover, the stop-and-go strategy with chemotherapy can maintain patient survival while minimizing chemotherapy related side effects when compared to the traditional strategy of continuous chemotherapy. These observations prompted the inception of this trial with the hypothesis that a short course of FOFLOX therapy combined with immunotherapy will likely have similar activity to that of continuing FOFLOX until disease progression when combined with immunotherapy. We also will examine the hypothesis that low dose radiotherapy can further augment immunotherapy efficacy. Methods: This is a multicenter, randomized phase II study examining Nivo alone vs radiation therapy (RT) with Nivo in subjects who did not have disease progression with 3 months of FOLFOX + Nivo. Subjects with advanced unresectable or metastatic GEA cancer are eligible. All subjects will receive FOLFOX + Nivo therapy. Subjects who demonstrate at least stable disease, on their first imaging assessment at 2 months will receive 1 additional month of FOLFOX + Nivo, and then will be randomly assigned at a 1:1 ratio to receive either Nivo alone or Nivo + RT. After 4 mos of therapy, patients who remain on study will receive Nivo Q4WKly. The primary endpoint is to demonstrate that the addition of fractionated radiation to immunotherapy is associated with an improvement in the 12-month progression-free survival (PFS) proportion from 25% (i.e., historical control estimate; Nivo alone; Arm A) to approximately 50% (i.e., with the fractional radiation and Nivo; Arm B). A key secondary aim is to demonstrate that short course FOLFOX of 3 months + Nivo is similar in efficacy to continuing FOLFOX until disease progression. Another secondary aim of this study is to demonstrate safety of the combination of fractionated RT + Nivo. Target sample size is 74 patients. The study is now open at six sites across the United States. Clinical trial information: NCT04021108.
Outcomes of patients with germ cell tumors diagnosed with stage I disease who subsequently received high dose chemotherapy (HDCT) with peripheral stem cell transplant (PBSCT) following failure of initial therapy for metastatic disease: The Indiana University experience.
Authors: Stephen B Benzinger, Ryan Ashkar, Rafat Abonour, Mohammad Issam Abu Zaid, Nabil Adra, Lawrence H. Einhorn, Nasser H. Hanna
Journal: Journal of Clinical Oncology (2021)

5029 Background: Pts with stage I testicular germ cell tumors (GCT) have a 15-year DFS of 99%. However, 1% are not cured, despite orchiectomy and systemic therapy at relapse. Predictive variables for relapse in this small population have not been identified. Methods: Pts undergoing HDCT with PBSCT as salvage therapy for relapsed GCT after an initial diagnosis of stage I disease managed with orchiectomy and surveillance were evaluated from a database at Indiana University. Patient demographics, disease characteristics, adherence to standard surveillance guidelines for stage I disease, prognostic variables, treatment received in the first-line setting, pattern of relapse, and outcomes were analyzed. Results: From 1/92 to 10/19, 71 pts (34 seminoma, 37 NSGCT) initially diagnosed with stage I GCT managed with orchiectomy and surveillance but subsequently relapsed and eventually required HDCT with PBSCT were identified. Median f/u time was 5.1 years (range, 1.1-18.8). Median age was 34.1. First-line chemo consisted of BEP or EP in most pts. Risk category at relapse: good/intermediate/poor (52/8/11). Pattern of initial relapse included 22 (seminoma n=13, NSGCT n=9) with RPLN only. Relapse and death after HDCT occurred in 2 of these 22 pts. Strict adherence to standard surveillance guidelines was observed in 62/71 pts. Relapse and/or death after HDCT occurred in 3 of 9 with inadequate surveillance follow-up. At a minimum of 1 yr follow-up, 54 of 71 (76%) remain alive, including 47 (66%) who have no evidence of disease (NED). Conclusions: Most patients in this series progressed despite appropriate surveillance and first-line chemotherapy. Pattern of relapse was also not indicative of further progression in most patients. Further investigation should evaluate disease biology that puts patients with potentially easily curable disease at risk of multiple relapses.[Table: see text]
Improvement in incident resolution time with implementation of an electronic patient management solution at a community oncology practice.
Authors: Lalan S. Wilfong, Amila Patel, Lance Ortega, Rhonda Boren, Ben Pearson, Terry Lynn Jensen, Holly Books, Kathryn Elizabeth Hudson, Debra A. Patt
Journal: Journal of Clinical Oncology (2021)

1578 Background: Value-based care models such as the Oncology Care Model incentivize practices to reduce hospitalizations and emergency department (ED) visits. Texas Oncology found that most ED visits occurred during regular business hours. Prolonged patient call back times were consistently rated poorly on satisfaction surveys and often led to ED visits for symptoms that could be managed in our offices. We partnered with Navigating Cancer (NC) to implement an electronic patient management technology solution. Methods: For each of our 200 locations, call volume was estimated based on clinic volume. We then reallocated or hired dedicated triage nurses and operators. Incoming calls were entered into the NC dashboard by operators as incidents which were routed based on symptom priority following system generated prompts. Incident volumes and resolution times were tracked. We instituted PDSA cycles at all locations with a goal of less than 90-minute resolution of symptom-related incidents Utilizing the electronic dashboard allowed us to continue this initiative during the COVID-19 public health emergency as our staff could work remotely. Nurses were able to document if a potential ED visit was avoided. These data points allowed our practice to establish comprehensive and strategic actions plans for quality improvement. Results: We finalized implementation of the system in February of 2020. Total incidents for 2020 were over 1 million, averaging over 5000 per location. Resolution time for all incidents started at 3.2 hours pre-implementation and improved to 2.2 hours in December of 2020. Resolution times for symptom-related incidents started at 2.3 hours pre-implementation and ended at 1.5 hours in December of 2020 with over 60% resolved under one hour. 8% of symptom-related incidents resulted in definite or probable ED avoidances by nursing assessment. Shortness of breath, vomiting, chills, and weakness were the top symptom types addressed for ED avoidances. Conclusions: An electronic patient management solution with PDSA cycles of quality improvement can markedly reduce call back times, especially for symptom related calls. We believe managing symptoms in a timely fashion will lower ED visits and hospitalizations as well as improve patient satisfaction. We will report on these outcomes once available.[Table: see text]
Phase 1 expansion trial of the LSD1 inhibitor seclidemstat (SP-2577) with and without topotecan and cyclophosphamide (TC) in patients (pts) with relapsed or refractory Ewing sarcoma (ES) and select sarcomas.
Authors: Damon R. Reed, Sant P. Chawla, Bhuvana Setty, Leo Mascarenhas, Paul A. Meyers, Jonathan Metts, Douglas James Harrison, Stephen L. Lessnick, Brian D. Crompton, David Loeb, David D. Stenehjem, David S. Wages, Daniela Y. Santiesteban, Nadeem Q. Mirza, Steven G. DuBois
Journal: Journal of Clinical Oncology (2021)

TPS11577 Background: Several sarcomas possess chromosomal translocations in FET family members ( FUS, EWSR1, and TAF15) responsible for cancer development. Sarcomas caused by FET family gene rearrangements include ES, desmoplastic round cell small tumors (DSRCT), myxoid liposarcoma (ML), and several others. Lysine specific demethylase 1 (LSD1) is a critical protein for sarcoma development and progression through its colocalization and/or association with several FET family oncogenic transcription factors. This suggests that pharmacologic inhibition of LSD1 may be a therapeutic strategy. Seclidemstat (SP-2577, Salarius Pharmaceuticals) is an oral, first-in-class, small molecule with reversible, noncompetitive inhibition of LSD1 (IC 50 : 25–50 nM). In vitro and in vivo data demonstrate seclidemstat, or analogs, modulate EWS/ETS transcriptional activity, down-regulating oncogene expression and up-regulating tumor-suppressor gene expression, leading to significant tumor growth inhibition in ES mouse xenograft studies. Seclidemstat has shown in in vitro ES cell lines near additivity efficacy when added to TC. In in vitro studies of other FET-translocated sarcomas, including ML (FUS/DDIT3 fusion) and clear cell sarcoma (EWS/ATF1 fusion), seclidemstat showed anti-proliferative activity. In an ongoing Phase 1 trial investigating single agent seclidemstat in advanced solid tumors (NCT03895684), three pts with metastatic FET-translocated sarcomas had a median progression-free survival of 5.7 months (range: 4.3–7.2) with a best response of stable disease despite having a median of 5 (range: 1–7) prior therapies. Methods: This dose expansion Phase 1 study (NCT03600649) assesses seclidemstat at 900 mg PO BID, the recommended Phase 2 dose, in two expansion cohorts: a single agent expansion in select sarcoma pts (n = 30) and a safety lead-in dose escalation and expansion (n = 24) of seclidemstat combined with TC in pts with ES. Pts must be ≥12 years old, have ECOG performance status of 0 or 1, with a life expectancy &gt; 4 months. In the select sarcoma cohort, pts must have ML (n = 15) or other sarcomas with FET family translocations (n = 15) including DSRCT. One to 3 prior lines of therapy are allowed. In the ES combination cohort, up to 2 lines of prior therapy are allowed. Primary objective is safety/tolerability and secondary objective is efficacy. The trial is currently recruiting across 8 locations in the United States. Clinical trial information: NCT03600649.