tbuckley/cabot-search huggingface dataset:
Association of concomitant NSAID and immunotherapy on outcomes in patients with non-small cell lung cancer: Analysis of the National Veterans Health Administration Database.
Authors: Drew Moghanaki, William A. Stokes, Madhusmita Behera, Renjian Jiang, David Gutman, Felipe Giuste, Abigail Burns, Nikhil Sebastian, Selvi Ramalingam, Vidula Sukhatme, Michael C. Lowe, Suresh S. Ramalingam, Vikas Sukhatme
Journal: Journal of Clinical Oncology (2021)

9107 Background: Preclinical data suggests the efficacy of immune checkpoint inhibitors (ICI) may be enhanced with concomitant nonsteroidal anti-inflammatory (NSAID) medications. Real-world evidence to support investigating this hypothesis in prospective randomized trials are needed. Methods: A retrospective cohort study queried the VA Corporate Data Warehouse (VA-CDW) to identify patients diagnosed with NSCLC who were treated with ICI between 2010-18. Exposure to concomitant NSAID was determined whenever NSAID prescriptions were released from the VA pharmacy within 90 days of the first ICI infusion. Chi-square and ANOVA tests were used to compare baseline characteristics. The outcome of overall survival (OS) was measured from the start of ICI. Cox proportional hazard regression was used to adjust for demographic, clinical, tumor, and treatment characteristics. Results: The study cohort consisted of 3,415 patients with NSCLC treated with ICI, and 2,336 (64%) were exposed to concomitant NSAID. The median age was 69, male 97%, race: white 73%, black 21%, and 66% lived in urban areas. Most patients were initially diagnosed with stage III or IV disease (68%); tumor histology: adenocarcinoma 48% and squamous cell 38%. Comorbidity counts were 0 in 40%, 1-3 in 30%, and 4+ in 30%. Chemotherapy was delivered before ICI in 54% and concurrently with ICI in 31%. The most commonly used NSAIDs were aspirin (35%), ketorolac (11%), and ibuprofen (7%); 44% were exposed to more than one NSAID. With a median follow-up of 8 months, exposure to concomitant NSAIDs was associated with a longer OS (HR = 0.90; 0.83-0.98, p = 0.01) after adjusting for all available potential confounders on multivariable analyses. Longer OS persisted following propensity score matching (HR = 0.89; 0.82-0.97 p = 0.007). Other factors significant for OS on multivariable testing included use of chemotherapy after ICI (HR = 0.53 [0.40-0.69], p &lt; 0.001), concurrent chemotherapy during ICI (HR = 0.68 [0.62-0.74], p &lt; 0.001), younger age, black race, female gender, and adenocarcinoma histology. Among the various NSAIDs analyzed on the multivariable analyses, only diclofenac approached statistical significance (HR = 0.78 [0.59-1.03], p = 0.08). Limiting the comparison to patients exposed to diclofenac (n = 101) versus no NSAIDs (n = 1,298), the comparison demonstrated a similar trend for OS (HR = 0.79 [0.60-1.04], p = 0.094), although the association was attenuated after propensity-score matching (HR = 0.90 [0.63-1.29], p = 0.57). Conclusions: This retrospective cohort study of Veterans with NSCLC who were treated with ICI identified that concomitant receipt of NSAIDs is associated with longer OS.
Perpetrators of workplace bullying and gender discriminations experienced by women gynecologic oncologists.
Authors: Linda Hong, Lisa Rubinsak, Michelle F. Benoit, Deanna Gek Koon Teoh, Yevgenia Ioffe, Uma Chandavarkar, Amy Brockmeyer, Erin E. Stevens, Sarah Madhu Temkin
Journal: Journal of Clinical Oncology (2021)

11013 Background: A high prevalence of gender discrimination and harassment has been described among gynecologic oncologists (GOs). This study examined the work environment for women GOs and delineated the perpetrators of negative behaviors. Methods: An internet-based, IRB exempt survey of members of a 472-member Facebook group “Women of Gynecologic Oncology (WGO)” was conducted. Using REDcap survey platform, members provided demographics, practice infrastructure, personal experience with workplace bullying, gender discrimination, microaggressions, and outcomes. Demographic, practice and work environments and perpetrators of negative behaviors were summarized using descriptive statistics. Results: Between 7/20 and 8/19/2020, 250 (53%) of active WGO members participated in this survey. Most respondents were younger than 50 years old (93.6%); white (82.2%) and non-Hispanic (94.3%). A majority were married (84.7%) with children (75.2%). Practice environments included academic (152, 61.0%), private practice (31, 12.4%), and hospital employed (57, 22.9%). 89.9% supervised trainees. 130 (52.0%) respondents reported bullying, 140 (56.0%) gender discrimination, and 83% having experienced gender-based microaggressions. Age, race, ethnicity, practice setting, division director or chair gender or department reporting structure were not significantly associated with these experiences. Perpetrators of bullying, gender discrimination, and microaggressions were widely distributed (Table). Of those reporting bullying, 61 (46.6%) reported a male perpetrator, 25 (19.1%) female and 45 (34.4%) an equal gender distribution; of those reporting discrimination 105 (74.5%) reported a male perpetrator, 9 (6.4%) female and 27 (19.1%) an equal gender distribution. 32.9% of survey respondents acknowledged having been written up for speaking up in a way that would have been tolerated from a male colleague. 18.3% of respondents have changed jobs because of bullying; 13.5% because of discrimination. Conclusions: Women GOs report high rates of workplace bullying, gender discrimination, and microaggressions regardless of practice setting that often impact their careers. Perpetrators of these behaviors are multiple and varied. Proactive and deliberate interventions to improve the work environments for women GOs are urgently needed.[Table: see text]
COVID-19 and medical education: Rethinking student assessment—The Virtual Observational Standard Clinical Examination.
Authors: Mariana Abal, Lourdes Gil Deza, Ernesto Gil Deza, Marta Dragosky, Claudia Lorena Acuna, Alba Marin Ordoñez, Monica Montiel, Flavio A Tognelli, Leonel Smolje, Cesar Gonzalez, Maximiliano Brandon, Carlos Garcia Gerardi, Gaston Martin Reinas, María del Huerto Jaunarena, Natasha Gercovich, Edgardo G. J. Rivarola, Eduardo L. Morgenfeld, Felipe G. Gercovich
Journal: Journal of Clinical Oncology (2021)

11005 Background: The COVID-19 pandemic introduced new challenges for medical education. In particular, student assessment posed some of the most urging questions. How do we evaluate practical skills when our universities are on lockdown and our hospitals are working on a shortage of personnel? Is it possible to evaluate these skills via online means, mitigating the effects in students’ career development? This paper presents an online evaluation experience implemented at Instituto Oncológico Henry Moore-Universidad del Salvador, Buenos Aires in the postgraduate program of Clinical Oncology. The Virtual Observational Standard Clinical Examination (V-OSCE) is a technology-based adaptation of the Observational Standard Clinical Examination (OSCE) (JCO 34 (15), Abstract e18150, 2017) implemented in previous years. Methods: The V-OSCE took place in November 14, 2020 and consisted on a half-day evaluation during which students rotated through 8 stations (Table). The exam ran on three platforms: Blackboard Collaborate for the interactive elements of all stations; University online campus (Moodle platform) for student questionnaires, and Google Forms for the evaluators’ assessment of each student. Students and evaluators participated in various training sessions, and were given a month to practice before the exam. All interactions were recorded and an anonymous survey on students’ experience and opinions was conducted after the exam. Results: A total of 25 postgraduate Oncology students participated in the V-OSCE. 24 students (96%) completed all stations on time with minimum or no network connection issues. Student opinions: 24 students completed the exam experience anonymous survey; 23 found the exam tech-friendly and valued the practice time provided. When asked to score the exam in a scale of 1 to 10: 80% of the students ranked the exam with 9 or 10; and 20%, with 7 or 8. Conclusions: A) It is feasible to design new ways to assess medical students via online means. B) The experience of an OSCE can be translated to an online environment with minimum technological requirements. C) The COVID-19 pandemic effects are extensive, with serious implications in medical education. However, it has proved to be an opportunity to rethink our educational practices, design innovative formative experiences, and assess new skills that will remain significant even long after the pandemic has ended.[Table: see text]
Epidemiology and Genetics of Venous Thromboembolism and Chronic Venous Disease
Authors: Richard A. Baylis, Nicholas L. Smith, Derek Klarin, Eri Fukaya
Journal: Circulation Research (2021)

Venous disease is a term that broadly covers both venous thromboembolic disease and chronic venous disease. The basic pathophysiology of venous thromboembolism and chronic venous disease differ as venous thromboembolism results from an imbalance of hemostasis and thrombosis while chronic venous disease occurs in the setting of tissue damage because of prolonged venous hypertension. Both diseases are common and account for significant mortality and morbidity, respectively, and collectively make up a large health care burden. Despite both diseases having well-characterized environmental components, it has been known for decades that family history is an important risk factor, implicating a genetic element to a patient's risk. Our understanding of the pathogenesis of these diseases has greatly benefited from an expansion of population genetic studies from pioneering familial studies to large genome-wide association studies; we now have multiple risk loci for each venous disease. In this review, we will highlight the current state of knowledge on the epidemiology and genetics of venous thromboembolism and chronic venous disease and directions for future research.
Evaluating the user-perceived benefit of a virtual patient education and support community: LVNG With Lung Cancer.
Authors: Mona L. Martin, Kristin Bucklen, Lise J. Hall, Beth Sandy, Dann Wonser, Genevieve de Renne
Journal: Journal of Clinical Oncology (2021)

92 Background: The accessibility and quality of network support for people living with lung cancer (PLW) and their support partners (SP) can vary. Virtual platforms provide a unique opportunity for PLW/SP peer support and disease education; the challenge is to measure impact. Methods: Our aim was to determine user-perceived benefit of the Facebook-based virtual community LVNG With Lung Cancer ( https://www.facebook.com/LVNGWithLungCancerUS ). Qualitative interviews were conducted with community members aged ≥18 yrs and living with lung cancer or actively supporting someone who had lung cancer. Also, inbound community comments (Dec 2015–Oct 2016) were retrospectively analyzed and grouped by similarity of content. Results: 18 PLW and 2 SP were interviewed (N = 20, saturation of concept met within the first 10). Mean yrs since diagnosis was 2.75 (range 0.08–17). Of the total expressions of benefit (n = 513) made during the interviews, 32% focused on increased health knowledge, with most participants calling out cancer information, good health behaviors, and coping strategies as key community benefits. Social impacts of the community accounted for 28% of benefit expressions; having a forum to share experiences and having a supportive environment were most frequently cited. An additional 18% of benefit expressions revealed that the community gives members feelings of empowerment, including feeling less alone (55% of respondents) and feeling inspired to help others (40% of respondents). Benefits received from community membership led to behavioral change in many respondents: 55% asked their doctor more questions, 50% shared helpful experiences with other members, and 35% took a more active role in their healthcare. In a notable example, an SP member said the community provided her with the knowledge she needed to address her symptoms and fears with her doctor, who was hesitant to biopsy because she did not meet typical risk criteria. Her self-advocacy was successful and ultimately led to an early lung cancer diagnosis. Results from the retrospective analysis of actual postings (n = 24,336; all unique users during evaluation period: n = 12,187) reflected the themes patients offered during interviews as important reasons to participate: 63% of postings were asking for or sharing cancer information, 98% provided emotional support and/or understanding, and 84% were inspirational/optimistic. Conclusions: This dual approach of assessing real-world impact of a virtual Facebook community provided insight into the benefit that members derive and highlighted the integral role of support groups in patient-centric care. Importantly, once members’ emotional and educational needs were met, they were empowered and/or inspired to take positive actions leading to better health behaviors and increased quality of life – an outcome that may have wider applicability for diseases beyond lung cancer.
Treatment beyond progression with immune checkpoint inhibitors in advanced melanoma.
Authors: Pawel Sobczuk, Anna Malgorzata Czarnecka, Mateusz Spalek, Pawel Teterycz, Monika Dudzisz-Śledź, Tomasz Switaj, Pawel Rogala, Joanna Placzke, Katarzyna Kozak, Aneta Borkowska, Hanna Kosela-Paterczyk, Piotr Rutkowski
Journal: Journal of Clinical Oncology (2021)

e21541 Background: Immunotherapy (ITH) holds the possibility of tumor burden decrease after initial RECIST defined progression (PD). Clinical concept of treating of selected patients (pts) beyond PD is supported by this pseudoprogression phenomenon. The aim of this study was to evaluate real-life practice and outcomes related to treatment beyond progression (TBP) in melanoma patients. Methods: We evaluated advanced melanoma pts who started anti-PD1 treatment between 12/2015 and 12/2018 and identified pts who received TBP and had subsequent imaging to evaluate the tumor burden. Survival analyses were performed using the Kaplan-Meier method, Log-rank, chi-square and Fisher exact tests were used for comparison between groups. Data cut-off was 02/2021. Results: Of 399 subsequent melanoma pts treated, 57 (14%) patients received TBP. Anti-PD1 was 1st line treatment in 61.4% and 2nd line - in 38.6% of patients. 71.9% patients were diagnosed with skin, 7.0% - mucosal and 21.1% with FPI melanoma and 47.4% were BRAF mutated, 56.1% were male and 12.3% had 3 or more metastatic sites at treatment initiation. In this cohort median time to 1st PD (TTFP) was 4.43 months(m), while to 2nd PD (TTSP) – 8.01 m. On TBP 26.3% pts achieved objective response (OR), and next 42.1% - SD. 1st PD was reported most often as increase in 3 or more targets or one new lesion – both 22.8%; and in 24.6% cases involved central nervous system. In 56.8% second PD was observed in the same targets as 1st PD. 61.4% patients received multimodal treatment of ITH combined with radiation therapy – in 49.1%, surgery - 5.3% and both - 7.0%. There was no correlation of TTSP with gender, ECOG, initial disease stage or TNM, BRAF mutation, number of metastatic sites or pattern of progression. Multimodal treatment resulted in 13.6 m TTSP, while ITH alone - 8.0 m (p = 0.056). 1st line OR correlated with DCR on TBP while TTFP &gt; 6 m correlated with TTSP (HR = 0.53, 95%CI 0.28-0.99). Patients with 1st line CR – had median TTSP 16.4 m, with PR – 23.5 m, while those with PD – 5.1 m. Median OS after 1st PD was 26 months and correlated with OR on TBP. Conclusions: Selected clinically fit melanoma patients despite evidence of first radiographic progression may benefit from continued treatment with PD-1 inhibitors. Multidisciplinary treatment should be offered to these patients including radiosurgery or stereotactic radiotherapy of progressing loci. Molecular biomarkers of TTSP should be analyzed in prospective studies.
Brigatinib in Japanese patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC): First results from the J-ALTA tyrosine kinase inhibitor (TKI)-naive expansion cohort.
Authors: Masashi Kondo, Shunichi Sugawara, Toshihide Yokoyama, Toru Kumagai, Makoto Nishio, Koichi Goto, Yuichiro Ohe, Takashi Seto, Nobuyuki Yamamoto, Kentarou Kudou, Takayuki Asato, Pingkuan Zhang, Kazuhiko Nakagawa
Journal: Journal of Clinical Oncology (2021)

9042 Background: Brigatinib is a next-generation ALK inhibitor with demonstrated activity against ALK mutations. We report primary analysis results with brigatinib in Japanese patients with ALK-positive NSCLC who have not previously been treated with an ALK TKI in the phase 2 J-ALTA study (NCT03410108). Methods: J-ALTA, a multi-cohort study, included a TKI-naive expansion cohort. Patients in the TKI-naive cohort received brigatinib 180 mg qd with 7-day lead-in at 90 mg. Primary endpoint was 12-month progression-free survival (PFS) as assessed by an independent-review committee (IRC). Secondary endpoints included confirmed objective response rate (ORR; IRC- and investigator-assessed); IRC-assessed PFS and duration of response (DoR); overall survival (OS); intracranial PFS (iPFS by IRC); and safety. Results: A total of 104 patients were enrolled in the whole study; of these, 32 patients had TKI-naive NSCLC (median age, 60.5 y; 94% had adenocarcinoma; 22% had baseline brain metastases; 25% received prior chemotherapy). As of September 29, 2020, median follow-up was 14.2 months and 27 patients remained on treatment. IRC-assessed 12-month PFS was 93% (90% CI, 79–98). Confirmed ORR was 97% (90% CI, 84–100) by IRC, with 2 complete responses and 29 partial responses. Median DoR as assessed by the IRC was not mature; median PFS, iPFS, and OS were not reached. In the TKI-naive cohort, treatment-emergent adverse events (TEAEs) were reported in all 32 patients (most common: increased creatine phosphokinase, 81%; hypertension, 59%; diarrhea, 47%). Grade ≥3 TEAEs were reported in 91% of patients in this cohort (most common: increased creatinine phosphokinase, 44%; hypertension, 34%; increased lipase, 19%) and 75% of all patients. Three cases (9.4%) of interstitial lung disease/pneumonitis were reported in the TKI-naive cohort; all were grade 1 and occurred after day 15 of brigatinib treatment. Dose discontinuations/interruptions/reductions due to AEs in the TKI-naive cohort were 0%/94%/66%, respectively, and in the total study population were 5%/72%/41%. AE frequency and profile were similar in the TKI-naive and overall cohorts. Conclusions: In the J-ALTA TKI-naive cohort, brigatinib demonstrated substantial efficacy and manageable safety in the Japanese patient population. Brigatinib remains one of the treatment options in Japanese patients. Clinical trial information: NCT03410108.
Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial
Authors: Philippe Moreau, Meletios-Athanasios Dimopoulos, Joseph Mikhael, Kwee Yong, Marcelo Capra, Thierry Facon, Roman Hajek, Ivan Špička, Ross Baker, Kihyun Kim, Gracia Martinez, Chang-Ki Min, Ludek Pour, Xavier Leleu, Albert Oriol, Youngil Koh, Kenshi Suzuki, Marie-Laure Risse, Gaelle Asset, Sandrine Macé, Thomas Martin, Philippe Moreau, Meletios-Athanasios Dimopoulos, Joseph Mikhael, Kwee Yong, Marcelo Capra, Thierry Facon, Roman Hajek, Ivan Spicka, Ross Baker, Kim Kihyun, Gracia Martinez, Min Chang-Ki, Ludek Pour, Xavier Leleu, Albert Oriol, Koh Youngil, Kenshi Suzuki, Tom Martin, Hang Quach, Andrew Lim, Helen Crowther, Hanlon Sia, Cyrille Hulin, Mohamad Mohty, Gabor Mikala, Zsolt Nagy, Marta Reinoso Segura, Laura Rosinol, Munci Yagci, Mehmet Turgut, Mamta Garg, Gurdeep Parmar, Brad Augustson, Nelson Castro, Edvan Crusoe, Tomas Pika, Sosana Delimpasi, Kenichi Ishizawa, Anup George, Tatiana Konstantinova, Javier De La Rubia, Kim Sung-Hyun, Angelo Maiolino, Anthony Reiman, Richard LeBlanc, Shigeki Ito, Junji Tanaka, Alexander Luchinin, Irina Kryuchkova, Joaquin Martinez, Jesse Shustik, Lionel Karlin, Anargyros Symeonidis, Miklos Egyed, Mario Petrini, Michele Cavo, Michihiro Uchiyama, Hilary Blacklock, Mutlu Arat, James Griffin, Hannah Hunter, Tonda Buck, Achilles Anagnostopoulos, Konstantinos Konstantopoulos, Tamas Masszi, Sara Bringhen, Barbara Gamberi, Yawara Kawano, Kim Jin Seok, Hakan Ozdogu, Fahir Ozkalemkas
Journal: The Lancet (2021)
Novel Peptide-drug Conjugate Melflufen Efficiently Eradicates Bortezomib-resistant Multiple Myeloma Cells Including Tumor-initiating Myeloma Progenitor Cells
Authors: Konstantin Byrgazov, Andrej Besse, Marianne Kraus, Ana Slipicevic, Fredrik Lehmann, Christoph Driessen, Lenka Besse
Journal: HemaSphere (2021)

Introduction of the proteasome inhibitor bortezomib has dramatically improved clinical outcomes in multiple myeloma. However, most patients become refractory to bortezomib-based therapies. On the molecular level, development of resistance to bortezomib in myeloma cells is accompanied by complex metabolic changes resulting in increased protein folding capacity, and less dependency on the proteasome. In this study, we show that aminopeptidase B, encoded by the RNPEP gene, is upregulated in bortezomib-resistant myeloma cell lines, and in a murine in vivo model. Moreover, increased RNPEP expression is associated with shorter survival in multiple myeloma patients previously treated with bortezomib-containing regimens. Additionally, expression is increased in plasma cell precursors, a B-lymphoid compartment previously associated with myeloma stem cells. We hypothesized that increased aminopeptidase B expression in aggressive myeloma clones may be used therapeutically toward elimination of the cells via the use of a novel peptide-drug conjugate, melphalan flufenamide (melflufen). Melflufen, a substrate of aminopeptidase B, efficiently eliminates bortezomib-resistant myeloma cells in vitro and in vivo, and completely suppresses clonogenic myeloma growth in vitro at subphysiological concentrations. Thus, melflufen represents a novel treatment option that is able to eradicate drug-resistant myeloma clones characterized by elevated aminopeptidase B expression.
Allogeneic Stem Cell Transplantation Platforms With Ex Vivo and In Vivo Immune Manipulations: Count and Adjust
Authors: Moniek de Witte, Laura G. M. Daenen, Lotte van der Wagen, Anna van Rhenen, Reiner Raymakers, Kasper Westinga, Jürgen Kuball
Journal: HemaSphere (2021)

Various allogeneic (allo) stem cell transplantation platforms have been developed over the last 2 decades. In this review we focus on the impact of in vivo and ex vivo graft manipulation on immune reconstitution and clinical outcome. Strategies include anti-thymocyte globulin- and post-transplantation cyclophosphamide-based regimens, as well as graft engineering, such as CD34 selection and CD19/αβT cell depletion. Differences in duration of immune suppression, reconstituting immune repertoires, and associated graft-versus-leukemia effects and toxicities mediated through viral reactivations are highlighted. In addition, we discuss the impact of different reconstituting repertoires on donor lymphocyte infusions and post allo pharmacological interventions to enhance tumor control. We advocate for precisely counting all graft ingredients and therapeutic drug monitoring during conditioning in the peripheral blood, and for adjusting dosing accordingly on an individual basis. In addition, we propose novel trial designs to better assess the impact of variations in transplantation platforms in order to better learn from our diversity of “counts” and potential “adjustments.” This will, in the future, allow daily clinical practice, strategic choices, and future trial designs to be based on data guided decisions, rather than relying on dogma and habits.