tbuckley/cabot-search huggingface dataset:
Isatuximab, lenalidomide, dexamethasone and bortezomib in transplant-ineligible multiple myeloma: the randomized phase 3 BENEFIT trial
Authors: Xavier Leleu, Cyrille Hulin, Jerome Lambert, Arthur Bobin, Aurore Perrot, Lionel Karlin, Murielle Roussel, Lydia Montes, Brieuc Cherel, Thomas Chalopin, Borhane Slama, Marie-Lorraine Chretien, Kamel Laribi, Claire Dingremont, Christophe Roul, Clara Mariette, Sophie Rigaudeau, Claire Calmettes, Mamoun Dib, Mourad Tiab, Laure Vincent, Jacques Delaunay, Alberto Santagostino, Margaret Macro, Emmanuelle Bourgeois, Frederique Orsini-Piocelle, Julie Gay, Benoit Bareau, Noemie Bigot, François Vergez, Pierre Lebreton, Reza Tabrizi, Agathe Waultier-Rascalou, Laurent Frenzel, Ronan Le Calloch, Emilie Chalayer, Thorsten Braun, Florence Lachenal, Selim Corm, Celine Kennel, Rakiba Belkhir, Jean-Sebastien Bladé, Bertrand Joly, Valentine Richez-Olivier, Helene Gardeney, Helene Demarquette, Daniela Robu-Cretu, Laurent Garderet, Muriel Newinger-Porte, Amine Kasmi, Bruno Royer, Olivier Decaux, Bertrand Arnulf, Karim Belhadj, Cyrille Touzeau, Mohamad Mohty, Salomon Manier, Philippe Moreau, Hervé Avet-Loiseau, Jill Corre, Thierry Facon
Journal: Nature Medicine (2024)

CD38-targeting immunotherapy is approved in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma (NDMM) that are transplant ineligible (TI) and is considered the best standard of care (SOC). To improve current SOC, we evaluated the added value of weekly bortezomib (V) to isatuximab plus lenalidomide and dexamethasone (IsaRd versus Isa-VRd). This Intergroupe Francophone of Myeloma phase 3 study randomized 270 patients with NDMM that were TI, aged 65-79 years, to IsaRd versus Isa-VRd arms. The primary endpoint was a minimal residual disease (MRD) negativity rate at 10-5 by next-generation sequencing at 18 months from randomization. Key secondary endpoints included response rates, MRD assessment rates, survival and safety. The 18-month MRD negativity rates at 10-5 were reported in 35 patients (26%, 95% confidence interval (CI) 19-34) in IsaRd versus 71 (53%, 95% CI 44-61) in Isa-VRd (odds ratio for MRD negativity 3.16, 95% CI 1.89-5.28, P < 0.0001). The MRD benefit was consistent across subgroups at 10-5 and 10-6, and was already observed at month 12. The proportion of patients with complete response or better at 18 months was higher with Isa-VRd (58% versus 33%; P < 0.0001), as was the proportion of MRD negativity and complete response or better (37% versus 17%; P = 0.0003). At a median follow-up of 23.5 months, no difference was observed for survival times (immature data). The addition of weekly bortezomib did not significantly affect the relative dose intensity of IsaRd. Isa-VRd significantly increased MRD endpoints, including the 18-month negativity rate at 10-5, the primary endpoint, compared with IsaRd. This study proposes Isa-VRd as a new SOC for patients with NDMM that are TI. ClinicalTrials.gov identifier: NCT04751877 .
Artificial Intelligence in the Provision of Health Care: An American College of Physicians Policy Position Paper
Authors: Nadia Daneshvar, Deepti Pandita, Shari Erickson, Lois Snyder Sulmasy, Matthew DeCamp
Journal: Annals of Internal Medicine (2024)

Internal medicine physicians are increasingly interacting with systems that implement artificial intelligence (AI) and machine learning (ML) technologies. Some physicians and health care systems are even developing their own AI models, both within and outside of electronic health record (EHR) systems. These technologies have various applications throughout the provision of health care, such as clinical documentation, diagnostic image processing, and clinical decision support. With the growing availability of vast amounts of patient data and unprecedented levels of clinician burnout, the proliferation of these technologies is cautiously welcomed by some physicians. Others think it presents challenges to the patient-physician relationship and the professional integrity of physicians. These dispositions are understandable, given the "black box" nature of some AI models, for which specifications and development methods can be closely guarded or proprietary, along with the relative lagging or absence of appropriate regulatory scrutiny and validation. This American College of Physicians (ACP) position paper describes the College's foundational positions and recommendations regarding the use of AI- and ML-enabled tools and systems in the provision of health care. Many of the College's positions and recommendations, such as those related to patient-centeredness, privacy, and transparency, are founded on principles in the ACP Ethics Manual. They are also derived from considerations for the clinical safety and effectiveness of the tools as well as their potential consequences regarding health disparities. The College calls for more research on the clinical and ethical implications of these technologies and their effects on patient health and well-being.
Sleep disturbance and fatigue in patients with ovarian cancer during chemotherapy and surgery compared to PARPi maintenance therapy.
Authors: Abigail Newell, Elizabeth A. Szamreta, Erica E. Fortune, Maria Belen Gonzalo, M. Claire Saxton, Elif Andac-Jones
Journal: Journal of Clinical Oncology (2024)

e23248 Background: Sleep disturbance and fatigue are prevalent among advanced ovarian cancer (OC) patients and are associated with poor health outcomes. It is unclear how sleep disturbance and fatigue vary across treatment timelines. This study evaluated how patients rate their sleep disturbance and fatigue levels at different points in their treatment trajectory. Methods: 200 U.S. patients with stage III/IV OC diagnosed in 2020-2023 were enrolled. Survey items asked patients to retrospectively assess their sleep disturbance and fatigue levels prior to diagnosis, during treatment, and presently. Sleep disturbance and fatigue were measured using a custom set of Patient-Reported Outcomes Measurement Information System (PROMIS) items based on previous findings. Most were receiving maintenance therapy (44%) or other treatments (34%), and 23% completed treatment. Nearly all participants received surgery (93%) and chemotherapy (97%). 44% of patients had received PARP inhibitor (PARPi) therapy, 18% received immunotherapy, and &lt; 10% received other therapies. Repeated sample t-tests compared symptom burdens. Results: Participants ranked sleep disturbance as most intense during chemotherapy (52%), followed by surgery (33%), hormone therapy (32%), and PARPi (15%). Most participants ranked fatigue as most intense during chemotherapy (67%), followed by hormone therapy (31%), surgery (20%), and PARPi therapy (17%). Paired t-tests show that among participants who received only surgery, chemotherapy and PARPi therapy, sleep disturbance was perceived to be significantly more intense during chemotherapy than when receiving PARPi, t(55) = -2.83, p = .006) and in the 2 weeks after surgery than PARPi therapy, (t(55) = -2.08, p = .043) ( Table). Fatigue was significantly more intense during chemotherapy than when receiving PARPi, (t(55) = -6.21, p &lt; .001) and following surgery than PARPi (t(54) = -4.16, p &lt; .001). Conclusions: OC patients experience intense sleep disturbance and fatigue and perceive levels differently depending on treatment. Chemotherapy was rated the worst for both sleep disturbance and fatigue compared to PARPi and other therapies. Targeted screening and psychosocial support can address these symptoms throughout treatment, especially after chemotherapy. [Table: see text]
Immunotherapy related patient-reported outcomes from five randomized controlled trials in patients with triple negative breast cancer: A systematic review.
Authors: Carrie Sha, Marie Liu, Johanna Goldberg, Larry Norton, Mark E. Robson, Iris Zhi
Journal: Journal of Clinical Oncology (2024)

e23167 Background: Immunotherapy (IO) has improved clinical outcomes in patients with early-stage Triple Negative Breast Cancer (TNBC) receiving neoadjuvant therapy and certain patient subsets in the metastatic setting. This study aims to evaluate IO-related Patient-Reported Outcomes (PRO) in patients older than 65 years. Methods: We searched Medline ALL (Ovid), Embase (Elsevier), Cochrane Central (Wiley), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform. The searches combined terms reflecting (1) the immune checkpoint inhibitors atezolizumab, durvalumab, and pembrolizumab; (2) breast cancer; and (3) randomized controlled trials. Results were limited to items published in English from 2013 through September 2023. We excluded review articles and clinical trial records without results. Two independent reviewers (C.S. and M.L.) screened the studies using the systematic review management tool Covidence, and conflicts were resolved by a third reviewer (W.I.Z.). We included studies that reported on PRO in adults with TNBC receiving any of the three immunotherapies of interest. Results: Five publications composed of two peer-reviewed papers and three abstracts were identified, including 3878 total patients and 3184 with PRO. Three pembrolizumab studies had 2643 total patients (2056 with PRO) and two atezolizumab studies (IMPASSION 130, IMPASSION 031) had 1235 total patients (1128 with PRO). The PRO analysis in KEYNOTE 522 included 1145 patients in the neoadjuvant phase and 847 in the adjuvant phase. The PRO analysis in KEYNOTE 355 included total 847 patients and 317 with Combined Positive Score (CPS) ≥10. No study specified PRO data for patients older than 65 years. Baseline completion rates for all studies were &gt; 80%. All studies used standardized PRO instruments, including the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC- QLQ C30) and its Breast Cancer Module (QLQ-BR23), the Functional Assessment of Cancer-Therapy-General (FACT-G GP5), and the EuroQol-5 Dimension (EQ-D5). All studies showed no statistical difference, or clinical meaningful decline in PRO endpoints between patients who received chemo with IO versus chemo with placebo, during and post treatment follow up. The PRO analysis from KEYNOTE 119, which included total 594 patients of which 187 had CPS ≥10, demonstrated that patients receiving single agent chemotherapy had worse PROs related to systemic therapy side effects and hair loss while the pembrolizumab group had decreased worry about future health. None included subgroup analysis by age, including patients older than 65 years. Conclusions: Our systematic review demonstrates that in both early and advanced TNBC, IO did not worsen PRO. Prospective and retrospective data in IO-related PRO in older patient population are needed.
Real world outcomes of 2,339 patients with early-stage triple-negative breast cancer (TNBC) treated in British Columbia.
Authors: Mairi Lucas, Stephen K. L. Chia, Caroline Speers, Caroline A. Lohrisch, Alan Nichol, Zahi Ibrahim Mitri
Journal: Journal of Clinical Oncology (2024)

e23274 Background: TNBC represents 15-20% of all breast cancers, and tends to exhibit more aggressive features, more frequent distant metastasis and overall worse prognosis than other breast cancer subtypes. The treatment landscape for early-stage TNBC has changed considerably in the last decade, with new additions to neoadjuvant therapy (NAT) aimed at improving pathologic responses and outcomes. In this study, we assess real world data regarding treatment and outcomes in those with early-stage TNBC. Methods: The BC Cancer Breast Cancer Outcomes Unit database contains prospectively collected data on patients residing in British Columbia and diagnosed with breast cancer since 1989. This retrospective study evaluated patients diagnosed with stage I-III TNBC from 2010 to 2019. During this era, regimens containing anthracyclines and taxanes were routinely used. TNBC was defined as per ASCO-CAP guidelines as ER≤1%, PR≤1% and negative HER 2 (0, 1+ by immunohistochemistry, or 2+ ISH negative). Outcomes of interest included event free survival (EFS), overall survival (OS), and pathologic complete response (pCR). Results: 2,339 patients withstage I-III TNBC were identified with a mean follow up of 6.5 years. OS was 87% (95% CI 85-88%) at 3-years and 79% (95% CI 77-80%) at 5-years. The presenting stage was a significant prognostic factor, with 5-year EFS of 89%, 81% and 51%- and 5-year OS of 90%, 80%, and 53% for stages I, II, and III, respectively. There was an increase in NAT use in 2019 (n = 82/230,35.7%) when compared to 2010 (n = 20/227, 8.8%). The most common neoadjuvant regimens used included anthracycline and taxane chemotherapies (n = 343,81.4%), with only a small number receiving neoadjuvant platinum chemotherapy (n = 52, 12.4%). Pathological complete response (pCR) was achieved in 24.5% (103/421) of patients who received NAT. Patients with pCR had improved 5- year EFS (91% vs. 57%, HR 0.26 [95% CI 0.15-0.45]) and 5-year OS (90% vs. 59%, HR 0.26 [95% CI 0.15-0.45]) compared to those with residual disease. The subgroup that received salvage capecitabine had a poor 3-year EFS at 22% but was enriched for patients with residual nodal disease after NAT (n = 77/130, 59.2%). Conclusions: This real-world study of TNBC in the era prior to routine immunotherapy (IO), highlights the poor prognosis of TNBC, particularly patients with locally advanced disease and those who did not achieve pCR, despite adjuvant capecitabine. This stresses the need for advances in NAT and salvage therapies for TNBC with residual disease at high risk of recurrence. [Table: see text]
Improving adequacy rates of bone marrow aspirate and core biopsies through training and a bedside X-ray device.
Authors: Rathnamitreyee Vegunta, Kuaybe Karakus Gulen, Snigdha Ghanta, Karen Seiter, Rajan Dewar
Journal: Journal of Clinical Oncology (2024)

e23228 Background: Bone marrow (BM) evaluation is crucial to the diagnosis of hematolymphoid disorders. WHO requires an adequate number of well-spread-out spicules in aspirates and defines an adequate BM core biopsy as ≥1.5 cm with at least 10 inter-trabecular areas (ITA). Gross examination of the core biopsy at the bedside can be misleading due to attached clot, thick periosteum, and cortical bone, or tangential biopsies, which histologically results in biopsy without adequate ITAs. Suboptimal BM biopsies hinder appropriate diagnosis, delay patient care, and may require the patient to undergo additional BM biopsies. Bedside image analysis via a cabinet x-ray system can be utilized as a point-of-care tool to assess the amount of evaluable marrow permitting re-biopsy at the time of the procedure. Methods: The study was conducted over 5 months at Westchester Medical Center. We retrospectively estimated BM adequacy rates by analyzing the aspirate quality and measuring the BM core biopsy length. Subsequently, a training demonstration to the proceduralist (fellows in training) by an experienced attending was performed and the adequacy rates were reassessed. BM biopsies were analyzed with a cabinet x-ray system, Faxitron, soon after biopsy, then subjected to routine histology and processing. High-resolution images of the core biopsy were obtained. The length of the core biopsy and the number of ITAs were calculated from the x-ray images. Measurement of the gross biopsy length and microscopic assessment of evaluable marrow were compared to the measurements obtained by x-ray imaging. Results: Our adequacy rates which met aspirate quality were 5% (1/20) pre-intervention and 65% (13/20) post-intervention. The aspirate smear quality improved after the demonstration technique to 65%. Only 13/53 core biopsies exceeded the WHO standard of 1.5 cm by microscopy, while 34/53 were grossly estimated to be &gt; 1.5 cm. There was general concordance between the number of ITAs and the length of core biopsies by microscopy. In approximately 20% of cases, the x-ray images highlighted suboptimal core biopsy ( &lt; 10 ITA/cortical bone/cartilage), which weren’t apparent by gross examination alone at the bedside. Utilizing x-ray image measurements, core biopsy fragment length was shown to be in concordance with microscopic estimation of length and number of ITAs. X-ray imaging readily identified clot sections (non-radiopaque), sclerotic cortical bone (absence of trabeculae), and periosteum (soft tissue shadow) in all 10 sub-1 cm biopsies. Conclusions: We conclude that a standard instruction technique of slide preparation can improve the quality of bone marrow aspirate. Core biopsy length and number of ITAs can easily be estimated using bedside point-of-care x-ray analysis to ensure adequate BM evaluations. We propose training and the routine use of bedside x-ray machine to improve the adequacy rates of BM biopsies.
An international expert consensus on improving the quality of care in patients with cancer by optimal central vascular access device selection.
Authors: Mohammad Jahanzeb, Ching Yang Wu, Howard J Lim, Kei Muro, Lichao Xu, Manjiri Somashekhar, S.P. Somashekhar, Xiaotao Zhang, Xiaoxia Qiu, Ying Fu, Mauro Pittiruti
Journal: Journal of Clinical Oncology (2024)

e23233 Background: In cancer patients (CPs), selection of an appropriate venous access is critical not only for delivering effective treatment, but also for enhancing patient comfort and quality of life to ensure treatment continuity. This consensus provides recommendations on the selection of the most appropriate central venous access device (CVAD) and its management in CPs. Methods: Eleven experts from three continents, including oncologists and healthcare professionals (HCPs) skilled in CVAD placement &amp; maintenance, convened electronically and face-to-face at a 2-day meeting. A comprehensive review of clinical trials &amp; guidelines on CVADs published between January 2013 and December 2023 from PubMed &amp; Cochrane Library was conducted. Preliminarily drafted statements were discussed by the panel and voted on. Evidence and panelists' expertise was employed in an anonymous polling for consensus. The final recommendations were approved by all panelists. Results: A summary of the panel’s consensus (ten statements) is shown in Table 1. Conclusions: The present consensus provides a robust clinical framework for HCPs to select the most suitable CVAD to facilitate therapy for CPs. [Table: see text]
Assessing the understanding and utilization of integrative oncology among patients with a history of cancer.
Authors: Meiqi Luo, Iqra Siddiqui, Ana Maria Lopez
Journal: Journal of Clinical Oncology (2024)

e23231 Background: Integrative oncology (IO) is an evidence-informed field of cancer care the utilizes mind-body practices, natural products, lifestyle medicine from different traditions alongside conventional therapies. Many of these components have growing evidence of benefit and are part of guideline recommendations. The Sidney Kimmel Cancer Center (SKCC) at Thomas Jefferson University has an integrative oncology program that sought to identify patients’ understanding of integrative health, assess their utilization of integrative medicine approaches, and define interest in IO consultations. Methods: Patients with a history of cancer or at high risk for cancer who presented for care at an SKCC clinical site received an electronic record invitation to complete a brief survey with binary and free-response questions regarding current knowledge, experiences, and interest in IO. At the end of the survey, patients also had the option to express interest in an IO consultations at SKCC. Results: Among 1327 responders, 900 (67.8%) were female, and 998 (75.2%) were between 45-75 years of age. Most were white (980, 73.9%), followed by Black or African American (279, 21.0%). Breast cancer (435, 32.8%) and hematologic cancers (277, 20.9%) were the most reported malignancies. Overall, 340 (26.4%) and 123 (9.27%) had previously utilized in-person IO services and virtual IO services, respectively. 887 (66.8%) patients reported that IO was never discussed during their care. 946 (71.3%) expressed interest in an IO consultation. Conclusions: Approximately a third of patients who completed the survey had previously used an IO modality. More than double that number expressed interest in and IO consultation. With the increasing evidence of benefit for IO care and the inclusion of these recommendations in clinical guidelines, expansion of IO services is indicated. IO consultations would address knowledge gaps, enhance implementation of guideline-based care, and, perhaps, improve clinical outcomes.
In cryptogenic stroke and atrial cardiopathy, apixaban did not reduce recurrent stroke vs. aspirin
Authors: Thalia S. Field
Journal: Annals of Internal Medicine (2024)

Source CitationKamel H, Longstreth WT Jr, Tirschwell DL, et al; ARCADIA Investigators. Apixaban to prevent recurrence after cryptogenic stroke in patients with atrial cardiopathy: the ARCADIA randomized clinical trial. JAMA. 2024;331:573-581. https://pubmed.ncbi.nlm.nih.gov/38324415/AbstractClinical Impact RatingsGIM/FP/GP: Neurology:
Lessons learned in migrating from one commercial genetics decision-support tool to another: Assessment of data integrity and utilization readiness.
Authors: Calvin Le, Kevin Tatunay, Mercy Y. Laurino, Marianne E. Dubard-Gault
Journal: Journal of Clinical Oncology (2024)

e23232 Background: Rapid advancements in health information technology have greatly influenced how clinicians engage with patient health data. In the context of clinical genetics, the electronic health record (EHR) often contains a wide array of data to identify patients at elevated risk for hereditary cancer syndromes. However, these data often exist in multiple forms and disparate locations, which in the presence of numerous commercial EHR solutions, results in significant variations in how institutions codify genetic data. Furthermore, within an institution, there is often internal pressure to migrate from one support tool to another, necessitating a focus on data integrity during such a transition. Methods: Fred Hutchinson Cancer Center (Fred Hutch) is a large academic cancer care center associated with the University of Washington. Between July and December 2023, the Fred Hutch Clinical Cancer Genetics and Genetic Counseling Service migrated their family history database from commercial pedigree software, Progeny, to another commercial pedigree and decision-support tool, CancerIQ. Following completion of the data migration on more than 13,000 patient records, study team planned to review a total of 500 randomly selected patient charts in both support tools. Each chart was reviewed to determine: (1) the presence of genetic intake information, (2) the presence and results of genetic testing, if available, and (3) whether the patient met National Comprehensive Cancer Network (NCCN) criteria for testing. A chart was noted to be concordant between the two support tools if there was agreement in all three of the above. Results: So far, a total of 240 patient charts were reviewed between the two support tools. Of these, 226 (94.2%) were noted to be fully concordant. Of the 14 charts that were noted to be discordant, the distribution of the discordant data was: 5 charts differed on whether genetic testing had been ordered, 5 charts differed on the results of the testing (often omitting one or more variants), and 4 differed on whether the patient met NCCN criteria for testing. Conclusions: At our institution, there was high data integrity following migration from one commercial and pedigree-generating software solution to another. While these results can ease clinician concerns following such support tools transitions, it also highlights areas for improvement in how family and patient genetic data is recorded.