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Background: In non-small cell lung cancer (NSCLC), social determinants of health (SDOHs) influence treatment, but SDOHs with geographic precision are infrequently used in real-world research due to privacy considerations. This research aims to characterize the influence of census-tract level SDOHs on treatment for stage I and IIa NSCLC., Methods: Patients diagnosed between 1/1/17 and 9/30/22 with stages I and IIa NSCLC in the Syapse Learning Health Network had their addresses geocoded and linked to five census tract-level indicators of SDOH (social vulnerability index (SVI), percent (%) housing burden, % broadband internet access, primary care shortage area, and rurality). Clinical and demographic characteristics were ascertained from medical records. Nested multinomial logistic regression models estimated associations between SDOHs and initial treatment using two-sided Wald tests. The collective statistical significance of SDOHs was assessed with a likelihood ratio test (LRT) comparing nested models. Descriptive statistics described time-to-treatment-initiation., Results: Among 3595 patients, 58% were initially treated with surgery, 29% with radiation, and 12% with "other." Two SDOH variables were associated with increased relative risk ratios (RRR) for radiation therapy compared to surgery: living in primary care shortage areas (RRR 1.61, 95% CI: (1.23-2.10)) and living in non-metropolitan areas (RRR 1.45 (1.02-2.07)). The LRT suggested that the five SDOH variables collectively improved the treatment model. Further, patients in areas with high SVI, low internet access, and high housing-burden initiated treatment later., Conclusion: When using precise estimates of geospatial SDOHs, these measures were associated with treatment, and should be considered in analyses of cancer outcomes., (© The Author(s) 2024. Published by Oxford University Press.)

Objectives: Lisocabtagene maraleucel (liso-cel; Breyanzi), an autologous chimeric antigen receptor T-cell therapy, has demonstrated efficacy and safety in relapsed/refractory large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma, and mantle cell lymphoma. Outpatient monitoring after liso-cel administration has shown lower health care resource utilization and cost and high patient satisfaction. However, outpatient monitoring programs require well-designed processes with collaborations from multiple stakeholders across several facilities. The study objective is to provide learnings and key considerations from nurses and advanced practice providers (APP) with experience setting up and managing liso-cel outpatient monitoring programs., Data Source: Author experience gathered from 3 institutions at 2 workshops., Results: In the reviewed programs, patients are discharged on the same day after liso-cel infusion and observation. They are required to remain within a short distance of the facility for ≥4 weeks with admission to treatment facilities upon experiencing adverse events (AE). Nurses/APPs report several key features of successful programs: flexibility to carry out essential roles/functions based on institution's resources and staff structure, a phased or hybrid (hospital/clinic) approach to program launch, a core team to run and guide the program, robust training for staff, options to tailor AE monitoring based on institution guidelines, and coordinated transitions between multiple stakeholders and facilities., Conclusions: Nurses/APPs are critical contributors to liso-cel outpatient monitoring programs. Success in providing appropriate, complex individualized care in these programs can be achieved by using a multistakeholder approach with appropriate staff and patient/caregiver training and careful coordination across multiple functions and facilities., Implications for Nursing Practice: The learnings and resources presented may provide insight to considerations around the development of a cell therapy outpatient monitoring program. However, the information provided here should be taken together with other relevant resources and guidelines and should be adapted to align with the institution's own guidelines., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: NM declares support from Bristol Myers Squibb for the preparation of this manuscript and participation on the Bristol Myers Squibb PAN CAR T live roundtable advisory board. JM, CCL, and LH have no conflicts to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Over the past decade, treatment recommendations for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) have shifted from traditional chemoimmunotherapy to targeted therapies. Multiple new therapies are commercially available, and in many cases a lack of randomized clinical trial data makes selection of the optimal treatment for each patient challenging. Additionally, many patients continue to receive chemoimmunotherapy in the US, suggesting a gap between guidelines and real-world practice. The Lymphoma Research Foundation convened a workshop comprised of a panel of CLL/SLL experts in the US to develop consensus recommendations for selection and sequencing of therapies for patients with CLL/SLL in the US. Herein, the recommendations are compiled for use as a practical clinical guide for treating providers caring for patients with CLL/SLL, which complement existing guidelines by providing a nuanced discussion relating how our panel of CLL/SLL experts in the US care for patients in a real-world environment., (Copyright © 2024 American Society of Hematology.)

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This is a comprehensive review of intraoperative, early postoperative, and late postoperative complications of Per Oral Endoscopic Myotomy with a focus on prevention, intraoperative management, and postoperative management., Competing Interests: Disclosure F. Khazoom: None. B.E. Louie: Consultant, Implantica; Data and Safety Monitoring Board: Omega Cuff, Aplos Medical., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rationale: Intrapleural enzyme therapy (IET) with tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) has been shown to reduce the need for surgical intervention for complicated parapneumonic effusion/empyema (CPPE/empyema). Failure of IET may lead to delayed care, and increased length of stay., Objective: The goal of this study was to identify risk factors for failure of IET., Methods: We performed a multicenter, retrospective study of patients who received IET for the treatment of CPPE/empyema. Clinical and radiological variables at the time of diagnosis were included. We compared four different machine learning classifiers (L1-penalized logistic regression, support vector machine (SVM), XGBoost and LightGBM) by multiple bootstrap-validated metrics, including F-beta to demonstrate model performances., Results: 466 participants who received IET for pleural infection were included from five institutions across the United States. Resolution of CPPE/empyema with IET was achieved in 78% (n=365). SVM performed superior with median F-beta of 56%, followed by L1-penalized logistic regression, LGBM and XGBoost. Clinical and radiological variables were graded based on their ranked variable importance. The top two significant predictors of IET failure using SVM were the presence of an abscess/necrotizing pneumonia (17%) and pleural thickening (13%). Similarly, LightGBM identified abscess/necrotizing pneumonia (35%) and pleural thickening (26%) and XGBoost indicated pleural thickening (36%) and abscess/necrotizing pneumonia (17%) as the most significant predictors of treatment failure. Predictors identified by L1-penalized logistic regression model were pleural thickening (18%) and pleural fluid LDH (9%)., Conclusions: The presence of abscess/necrotizing pneumonia and pleural thickening consistently ranked among the strongest predictors of IET failure in all machine learning models. The difference in rankings between models may be a consequence of the different algorithms used by each model. These results indicate that the presence of abscess/necrotizing pneumonia, and pleural thickening may predict IET failure. These results should be confirmed in larger studies.

Background: Clinical studies have demonstrated that intraoperative molecular imaging (IMI) with pafolacianine identifies occult pulmonary lesions that are not identified by preoperative CT or by intraoperative inspection techniques in ∼20% of patients. In this study we provide a description of occult lesion clinical data and evaluate characteristics so that surgeons can better incorporate this emerging technology into clinical decision making., Methods: Participants (n=100) enrolled in a Phase 3 trial of IMI with pafolacianine during pulmonary resection (ELUCIDATE, NCT04241315) were identified. Participants underwent preoperative computed tomography (CT)with 1.25mm slices. Variables and lesion characteristics were analyzed. Positive predictive value and false positive rates were tabulated for IMI fluorescent lesions with predictors of malignant versus benign occult lesions described., Results: IMI identified 29 occult lesions in 23 (23%) participants. Seventeen of 29 (58%) lesions were identified within the same lobe as known lesions; 12 of 29 (42%) identified in a different lobe from the suspicious nodule known by preoperative assessment. Twenty-three of 29 (79%) of occult lesions found by IMI were resected with an additional wedge resection. Ten of 29 (34%) lesions identified by IMI were malignant. There was no additional morbidity in participants with lesions resected. With pafolacianine, 7 participants had a synchronous primary stage I lung cancer identified and one subject had additional metastases identified. ., Conclusions: IMI with pafolacianine identifies occult malignant lesions during pulmonary resection despite thorough preoperative imaging and intraoperative assessment by experienced surgeons., (Copyright © 2024. Published by Elsevier Inc.)

The Association of Program Directors for Colon and Rectal Surgery (APDCRS) has sponsored a standardized robotics course for colorectal and minimally invasive surgery fellows since 2011. The study objective was to assess the impact of the APDCRS-sponsored course on surgical approaches adopted by young colorectal surgeons before, during, and after fellowship. An internet-based survey was administered to 2014-2022 ACGME-accredited colorectal surgery program graduates. Study variables were summarized using frequencies and proportions. Survey response rate was 43.2%. Laparoscopic and robotic volumes were consistently higher than open and hand-assist laparoscopic volumes over the study period. About 70.0% of fellows performed ≥ 20 laparoscopic cases before 2017, and over 80% had experience with ≥ 20 laparoscopic cases during/after 2017. An increasing trend of performing ≥ 20 robotic colorectal cases during fellowship was observed (before 2017: 75.0%, 2018-2019: 76.9%, and 2021-2022: 84.8%). Multivariate logistic regression analysis showed that higher robotic volume (≥ 25 colorectal cases) during general surgery residency increased odds of performing ≥ 50 robotic cases during fellowship (OR: 4.38, 95% CI 0.88, 26.1). Higher robotic volumes during fellowship correlated with higher robotic volumes in the first year of post-fellowship practice. 88.6% of respondents agree (21.0%) or strongly agree (67.6%) that the APDCRS robotics training course met expectations, and 83.8% agree or strongly agree that the course prepared them for post-graduate robotics practice. The APDCRS-sponsored robotics training course met expectations and prepared colorectal surgery fellows for adopting the robotic approach after graduation, with the majority of respondents reporting that they utilize robotics in their post-graduation colorectal practice., (© 2024. The Author(s).)

Bruton tyrosine kinase inhibitors (BTKi) have transformed the treatment of B-cell malignancies, but intolerance has often led to their discontinuation. The phase 1/2 BRUIN study evaluated pirtobrutinib, a highly selective non-covalent (reversible) BTKi, in patients with R/R B-cell malignancies (NCT03740529). Pirtobrutinib was investigated in 127 patients with intolerance to at least one prior BTKi therapy in the absence of progressive disease. The most common adverse event (AE) leading to BTKi discontinuation was cardiac disorders (n=40, 31.5%), specifically atrial fibrillation (n=30, 23.6%). The median follow-up was 17.4 months and the median time on pirtobrutinib was 15.3 months. The most common reasons for pirtobrutinib discontinuation were progressive disease (26.8%), AE (10.2%), or death (5.5%). The most frequent treatment-emergent AEs were fatigue (39.4%) and neutropenia (37.0%). Among patients who discontinued a prior BTKi for a cardiac issue, 75% had no recurrence of their cardiac AE. No patient discontinued pirtobrutinib for the same AE that led to discontinuation of the prior BTKi. In 78 CLL/SLL and 21 MCL patients intolerant to prior BTKi, ORR to pirtobrutinib was 76.9% and 81.0%, respectively. Median PFS for CLL/SLL was 28.4 months and was not estimable for MCL. These results suggest that pirtobrutinib was safe, well-tolerated, and an efficacious option in patients with prior BTKi-intolerance.

Purpose: Targeted Agent and Profiling Utilization Registry is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and targetable genomic alterations. Two cohorts of patients with cyclin-dependent kinase inhibitor 2A ( CDKN2A )-mutated tumors treated with palbociclib are reported: one with head and neck cancer (HNC) with both squamous and nonsquamous cell histologies, and one with histology-pooled (HP) cancers., Methods: Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration. For the HNC cohort, Simon's two-stage design with a null DC rate of 15% versus 35% (power = 0.85; α = .10) was used. For the HP cohort, the null hypothesis of a DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points included OR, safety, progression-free survival, overall survival, duration of response, and duration of SD., Results: Seventy patients with HNC (N = 28) or HP cancers (N = 42) were treated with palbociclib. For the HNC cohort, DC and OR rates were 40% (one-sided 90% CI, 27 to 100) and 4% (95% CI, <1 to 18), respectively. The null hypothesis was rejected ( P = .002). For the HP cohort, DC and OR rates were 13% (one-sided 90% CI, 6 to 100) and 5% (95% CI, <1 to 17), respectively. The null hypothesis was not rejected. Thirty-one of 70 patients experienced treatment-related grade 3 to 4 adverse events (AEs) or serious AEs, the most common including neutropenia, thrombocytopenia, and leukopenia., Conclusion: Palbociclib met prespecified criteria to declare a signal of activity in patients with HNC with CDKN2A alterations, but not in the HP cohort.

High-Grade Serous Ovarian Cancer (HGSOC) originates from fallopian tube (FT) precursors. However, the molecular changes that occur as precancerous lesions progress to HGSOC are not well understood. To address this, we integrated high-plex imaging and spatial transcriptomics to analyze human tissue samples at different stages of HGSOC development, including p53 signatures, serous tubal intraepithelial carcinomas (STIC), and invasive HGSOC. Our findings reveal immune modulating mechanisms within precursor epithelium, characterized by chromosomal instability, persistent interferon (IFN) signaling, and dysregulated innate and adaptive immunity. FT precursors display elevated expression of MHC-class I, including HLA-E, and IFN-stimulated genes, typically linked to later-stage tumorigenesis. These molecular alterations coincide with progressive shifts in the tumor microenvironment, transitioning from immune surveillance in early STICs to immune suppression in advanced STICs and cancer. These insights identify potential biomarkers and therapeutic targets for HGSOC interception and clarify the molecular transitions from precancer to cancer., Competing Interests: DECLARATION OF INTERESTS PKS is a co-founder and member of the BOD of Glencoe Software and member of the SAB for RareCyte, NanoString, and Montai Health; he holds equity in Glencoe and RareCyte. PKS is a consultant for Merck. RD is a member of the SAB for Repare Therapeutics and is a consultant for Light Horse Therapeutics and Abbvie. The other authors declare no outside interests.

Objective: Data on graded complications and their frequency after laparoscopic revisional antireflux and hiatal hernia surgery compared with primary surgery are lacking. We describe 30- and 90-day morbidity using the Clavien-Dindo classification., Methods: A total of 298 patients underwent revision surgery between 2003 and 2020 and were propensity matched to primary surgeries (1:2 ratio) based on age, sex, body mass index, American Society of Anesthesiology classification, Los Angeles grade esophagitis, presence of Barrett's, and indication for surgery. Complications were graded using the Clavien-Dindo classification, with the highest grade of complication reported per patient., Results: After matching, both groups had a majority of female patients, with a median age of 60 years and a median body mass index of 29.5 kg/m 2 . Most were healthy, with nonerosive esophagitis and modest levels of Barrett's esophagus. A laparoscopic Nissen fundoplication was most common; however, a partial fundoplication was more common in revisions. Mesh, relaxing incisions, and Collis were more common in revisional surgery. At 30 days, total complications were similar (23.5% [70/298] vs 20.6% [123/596], P = .373) with 1 death in each group. Minor complications (less than Clavien-Dindo 3A) were comparable. Patients undergoing revisional surgery experienced Clavien-Dindo 3B complications (4.7% [14] vs 0.8% [5], P > .001) more frequently, with esophageal obstruction requiring revision and esophageal/gastric leak being most common. Grade Clavien-Dindo 4 A/B complications were comparable in both groups. At 90 days, patients undergoing revisional surgery experienced overall complications (7.1% [21] vs 2.0% [12], P = .003), and Clavien-Dindo 3B complications (1.0% [3] vs 0, P = .037) more frequently, with intra-abdominal abscess washout being the most common Clavien-Dindo 3B complication., Conclusions: Revisional surgery results in similar total complications at 30 days, but additional complications can occur out to 90 days., Competing Interests: Conflict of Interest Statement Dr Louie discloses relationships with Implantica (Reflux Stop), consultant, and Aplos Medical (Omega Cuff), member, Data and Safety Monitoring Board. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

This multicenter, open-label, phase 1b study (ACE-LY-106) assessed the safety and efficacy of acalabrutinib, bendamustine, and rituximab (ABR) in treatment-naive (TN) and relapsed or refractory (R/R) mantle cell lymphoma (MCL). Patients received acalabrutinib from cycle 1 until disease progression or treatment discontinuation, bendamustine on days 1 and 2 of each cycle for up to 6 cycles, and rituximab on day 1 of each cycle for 6 cycles, continuing every other cycle from cycle 8 for 12 additional doses (TN cohort). Eighteen patients enrolled in the TN and 20 in the R/R cohort. Median duration of exposure to acalabrutinib was 34.0 and 14.6 months in the TN and R/R cohorts, respectively. No new safety risks were identified, and most adverse events (AEs) were grades 1 or 2. Thirteen patients from the TN cohort (72.2%) and 17 patients from the R/R cohort (85.0%) reported grade 3-4 AEs, most commonly neutropenia (TN: 38.9%, R/R: 50.0%). AEs leading to death were pneumonitis (n=1, TN cohort), COVID-19, and cerebrospinal meningitis (n=1 each, R/R cohort). Overall response was 94.4% and 85.0% in the TN and R/R cohorts, respectively; complete response rates were 77.8% and 70.0%, respectively. After a median follow-up of 47.6 months, median progression-free survival (PFS) and overall survival (OS) were not reached in the TN cohort. After a median follow-up of 20.4 months, median PFS was 28.6 months and OS was not reached in the R/R cohort. Results indicate that ABR was safe and efficacious, supporting further study in patients with TN MCL. ClinicalTrials.gov identifier: NCT02717624.

Background: People with HIV are both at elevated risk of lung cancer and at high risk of multimorbidity, which makes shared decision-making (SDM) for lung cancer screening (LCS) in people with HIV complex. Currently no known tools have been adapted for SDM in people with HIV., Research Question: Can an SDM decision aid be adapted to include HIV-specific measures with input from both people with HIV and their providers?, Study Design and Methods: This study used qualitative methods including focus groups of people with HIV and interviews with HIV care providers to adapt and iterate an SDM tool for people with HIV. Eligible participants were those with HIV enrolled in an HIV primary care clinic who met age and smoking eligibility criteria for LCS and HIV care providers at the clinic. Both the focus groups and interviews included semistructured discussions of SDM and decision aid elements for people with HIV. We used a framework-guided thematic analysis, mapping themes onto the Health Equity Implementation framework., Results: Forty-three people with HIV participated in eight focus groups; 10 providers were interviewed. Key themes from patients included broad interest in adapting LCS SDM specifically for people with HIV, a preference for clear LCS recommendations, and the need for positive framing emphasizing survival. Providers were enthusiastic about personalized LCS risk assessments and point-of-care tools. Both patients and providers gave mixed views on the usefulness of HIV-specific risk measures in patient-facing tools. Themes were used to adapt a personalized and flexible SDM tool for LCS in people with HIV., Interpretation: People with HIV and providers were enthusiastic about specific tools for SDM that are personalized and tailored for people with HIV, that make recommendations, and that inform LCS decision-making. Divergent views on presenting patient-facing quantitative risk assessments suggests that these elements could be optional but available for review. This tool may have usefulness in complex decision-making for LCS in this population and currently is being evaluated in a pilot prospective trial.

Background: Pleural effusions in post-operative thoracic surgery patients are common. Effusions can result in prolonged hospitalizations or readmissions, with prior studies suggesting mixed effects of pleural drainage on hypoxia. We aimed to define the impact of pleural drainage on pulse oximetry (SpO2) in post-thoracic surgery patients., Methods: A retrospective study of post-operative thoracic surgery patients undergoing pleural drainage was performed. SpO2 and supplemental oxygen (FiO2) values were recorded at pre- and post-procedure. The primary outcome was difference in pre-procedural and post-procedural SpO2., Results: We identified 95 patients with a mean age of 65 (SD - 13.8) years undergoing 122 pleural drainage procedures. Mean drainage volume was 619 (SD-423) mL and the majority of procedures (88.5 %) included a drainage of <1000 mL. SpO2 was associated with an increase from 94.0 % (SD-2.6) to 97.3 % (SD-2.0) at 24-h (p < 0.0001). FiO2 was associated with a decrease from 0.31 (SD-0.15) to 0.29 (SD-0.12) at 24-h (p = 0.0081). SpO2/FiO2 was associated with an increase from 344.5 (SD-99.0) to 371.9 (SD-94.7) at 24-h post-procedure (p < 0.0001)., Conclusions: Pleural drainage within post-operative thoracic surgery patients offers statistically significant improvements in oxygen saturation by peripheral pulse oximetry and oxygen supplementation; however the clinical significance of these changes remains unclear. Pleural drainage itself may be requested for numerous reasons, including diagnostic (fevers, leukocytosis, etc.) or therapeutic (worsening dyspnea) evaluation. However, pleural drainage may offer minimal clinical impact on pulse oximetry in post-operative thoracic surgery patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Inequitable access to care continues to hinder improvements in diagnosis and treatment of lung cancer. This review describes healthcare disparities in the changing landscape of non-small cell lung cancer (NSCLC) in the United States, focusing on racial, ethnic, sex-based, and socioeconomic trends. Furthermore, strategies to address disparities, overcome challenges, and improve patient outcomes are proposed. Barriers exist across lung cancer screening, diagnosis, and treatment regimens, varying by sex, age, race and ethnicity, geography, and socioeconomic status. Incidence and mortality rates of lung cancer are higher among Black men than White men, and incidences in young women are substantially greater than in young men. Disparities may be attributed to geographic differences in screening access, with correlating higher incidence and mortality rates in rural versus urban areas. Lower socioeconomic status is also linked to lower survival rates. Several strategies could help reduce disparities and improve outcomes. Current guidelines could improve screening eligibility by incorporating sex, race, and socioeconomic status variables. Patient and clinician education on screening guidelines and patient-level barriers to care are key, and biomarker testing is critical since ~ 70% of patients with NSCLC have an actionable biomarker. Timely diagnosis, staging, and comprehensive biomarker testing, including cell-free DNA liquid biopsy, may provide valuable treatment guidance for patients with NSCLC. Efforts to improve lung cancer screening and biomarker testing access, decrease bias, and improve education about screening and testing are needed to reduce healthcare disparities in NSCLC., Competing Interests: Declarations Competing interests Dr. Kurzrock reported receiving research funding from Boehringer Ingelheim, Debiopharm, Foundation Medicine, Genentech, Grifols, Guardant, Incyte, Konica Minolta, MedImmune, Merck Serono, OmniSeq, Pfizer, Sequenom, Takeda, and Top Alliance; receiving consultant and/or speaker fees and/or advisory board fees from Actuate Therapeutics, AstraZeneca, Bicara Therapeutics, Inc., Biological Dynamics, Caris, Datar Cancer Genetics, Eisai, EOM Pharmaceuticals, Iylon, Merck, NeoGenomics, Neomed, Pfizer, prosperdtx, Regeneron, Roche, TD2/Volastra, Turning Point Therapeutics, and XBiotech; having an equity interest in CureMatch, Inc. and IDbyDNA; serving on the board of CureMatch and CureMetrix, and being a cofounder of CureMatch.Dr. Chaudhuri reported receiving consultant and/or speaker fees and/or advisory board fees from Roche, Tempus, Geneoscopy, Illumina, Daiichi Sankyo, AstraZeneca, Myriad Genetics, Invitae, AlphaSights, DeciBio, Guidepoint, Agilent, DAVA Oncology, and Geneoscopy; having licensed technologies related to cancer biomarkers; and being a cofounder of Droplet Biosciences and LiquidCell Dx.Dr. Feller-Kopman reported receiving consultant fees from Daiichi Sankyo and AstraZeneca.Dr. Florez is a consultant/advisor to AstraZeneca, Merck, DSI, Regeneron Janssen, Bristol Myers Squib, NeoGenomics, and Pfizer.Dr. Gorden reported receiving speaker fees from AstraZeneca.Dr. Wistuba reported receiving research funding to the institution from 4D Molecular Therapeutics, Adaptimmune, Adaptive Biotechnologies, Akoya Biosciences, Amgen, Bayer, EMD Serono, Genentech, Guardant Health, HTG Molecular Diagnostics, Iovance Biotherapeutics, Johnson & Johnson, Karus Therapeutics, MedImmune, Merck, Novartis, OncoPlex Diagnostics, Pfizer, Takeda, and Novartis; receiving personal research funding from Pfizer and Bayer; receiving grants/contracts from Asuragen, Genentech/Roche, Bristol Myers Squibb, AstraZeneca/MedImmune, HTG Molecular Diagnostics, Merck, and Guardant Health; and receiving consultant fees from AstraZeneca/MedImmune, Asuragen, Bayer, Bristol Myers Squibb, Genentech/Roche, GlaxoSmithKline, Guardant Health, HTG Molecular Diagnostics, Merck, MSD Oncology, OncoCyte, Novartis, Flame Inc., Pfizer, Regeneron, Merus, and G1 Therapeutics., (© 2024. The Author(s).)

Background: Human epidermal growth factor receptor 2 protein (HER2)-positive (+) metastatic breast cancer (MBC) is an aggressive disease and patients often undergo multiple lines of therapy following HER2 targeted therapies. The most recent National Comprehensive Cancer Network (NCCN) guidelines recommend margetuximab plus chemotherapy as fourth-line or later therapy for HER2+/hormone receptor (HR) + or negative (-) MBC. The aim of this case series is to provide information regarding margetuximab utilization in clinical practice as later-line therapy in women with HER2+ MBC., Case Summaries: Margetuximab plus chemotherapy was used as fourth- or later-line treatment in patients who had received multiple HER2-targeted agents, including trastuzumab, pertuzumab, ado-trastuzumab emtansine, trastuzumab deruxtecan, tucatinib, and neratinib. Patients responded to margetuximab plus chemotherapy with real-world progression-free survival (PFS) of 3, 4, and 7 months., Conclusion: Clinical outcomes from three heavily pretreated patients with metastatic HER2+/HR+ MBC demonstrated that margetuximab plus chemotherapy resulted in real-world PFS comparable to that reported in the controlled pivotal clinical trial and support use of this targeted therapy option in appropriately identified patients., Competing Interests: RM has the following disclosures to report: Agendia, Amgen, Astra Zeneca, Daiichi Sankyo, Eisai, Genentech, Gilead, Hologic, Eli Lilly, Merck, Novartis, Pfizer, Puma, Sanofi, SeaGen, Stemline, Sermonix. Author KP was employed by Eversana. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mahtani, Harpalani, Yan, Phiel and Kovalenko.)

Artificial intelligence (AI) applications to medical care are currently under investigation. We aimed to evaluate and compare the quality and accuracy of physician and chatbot responses to common clinical questions in gynecologic oncology. In this cross-sectional pilot study, ten questions about the knowledge and management of gynecologic cancers were selected. Each question was answered by a recruited gynecologic oncologist, ChatGPT (Generative Pretreated Transformer) AI platform, and Bard by Google AI platform. Five recruited gynecologic oncologists who were blinded to the study design were allowed 15 min to respond to each of two questions. Chatbot responses were generated by inserting the question into a fresh session in September 2023. Qualifiers and language identifying the response source were removed. Three gynecologic oncology providers who were blinded to the response source independently reviewed and rated response quality using a 5-point Likert scale, evaluated each response for accuracy, and selected the best response for each question. Overall, physician responses were judged to be best in 76.7 % of evaluations versus ChatGPT (10.0 %) and Bard (13.3 %; p < 0.001). The average quality of responses was 4.2/5.0 for physicians, 3.0/5.0 for ChatGPT and 2.8/5.0 for Bard ( t -test for both and ANOVA p < 0.001). Physicians provided a higher proportion of accurate responses (86.7 %) compared to ChatGPT (60 %) and Bard (43 %; p < 0.001 for both). Physicians provided higher quality responses to gynecologic oncology clinical questions compared to chatbots. Patients should be cautioned against non-validated AI platforms for medical advice; larger studies on the use of AI for medical advice are needed., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Purpose: We present a phase I/II first-in-human trial evaluating the safety and efficacy of 50 mg and 200 mg doses of linvoseltamab, a B-cell maturation antigen × CD3 bispecific antibody in relapsed/refractory multiple myeloma (RRMM)., Methods: Phase II eligible patients had RRMM that either progressed on/after ≥three lines of therapy including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 antibody or was triple-class (PI/IMiD/anti-CD38) refractory. Phase II treatment was once a week through week 14 and then once every 2 weeks. Phase II 200 mg patients who achieved a ≥very good partial response by week 24 received linvoseltamab once every 4 weeks. The primary end point in phase II was overall response rate (ORR)., Results: Among the 117 patients treated with 200 mg, the median age was 70 years, 39% had high-risk cytogenetics, and 28% had penta-refractory disease. At a median follow-up of 14.3 months, the ORR was 71%, with 50% achieving ≥complete response (CR). In 104 patients treated with 50 mg at a median follow-up of 7.4 months, the ORR was 48%, with 21% achieving ≥CR. The median duration of response (DOR) for 200 mg patients (n = 83) was 29.4 months (95% CI, 19.2 to not evaluable). Among 200 mg patients, the most common adverse events included cytokine release syndrome (35.0% Gr1, 10.3% Gr2, 0.9% Gr3), neutropenia (0.9% Gr2, 18.8% Gr3, 23.1% Gr4), and anemia (3.4% Gr1, 4.3% Gr2, 30.8% Gr3). Immune effector cell-associated neurotoxicity syndrome occurred in 7.7% of patients (2.6% each Gr1, Gr2, Gr3). Infections were reported in 74.4% of patients (33.3% Gr3, 2.6% Gr4); infection frequency and severity declined over time., Conclusion: Linvoseltamab 200 mg induced deep and durable responses, with a median DOR of 29.4 months, in patients with RRMM with an acceptable safety profile.

Inhibition of histone lysine acetyltransferases (KATs) KAT6A and KAT6B has shown antitumor activity in estrogen receptor-positive (ER + ) breast cancer preclinical models. PF-07248144 is a selective catalytic inhibitor of KAT6A and KAT6B. In the present study, we report the safety, pharmacokinetics (PK), pharmacodynamics, efficacy and biomarker results from the first-in-human, phase 1 dose escalation and dose expansion study (n = 107) of PF-07248144 monotherapy and fulvestrant combination in heavily pretreated ER + human epidermal growth factor receptor-negative (HER2 - ) metastatic breast cancer (mBC). The primary objectives of assessing the safety and tolerability and determining the recommended dose for expansion of PF-07248144, as monotherapy and in combination with fulvestrant, were met. Secondary endpoints included characterization of PK and evaluation of antitumor activity, including objective response rate (ORR) and progression-free survival (PFS). Common treatment-related adverse events (any grade; grades 3-4) included dysgeusia (83.2%, 0%), neutropenia (59.8%, 35.5%) and anemia (48.6%, 13.1%). Exposure was approximately dose proportional. Antitumor activity was observed as monotherapy. For the PF-07248144-fulvestrant combination (n = 43), the ORR (95% confidence interval (CI)) was 30.2% (95% CI = 17.2-46.1%) and the median PFS was 10.7 (5.3-not evaluable) months. PF-07248144 demonstrated a tolerable safety profile and durable antitumor activity in heavily pretreated ER + HER2 - mBC. These findings establish KAT6A and KAT6B as druggable cancer targets, provide clinical proof of concept and reveal a potential avenue to treat mBC. clinicaltrial.gov registration: NCT04606446 ., (© 2024. The Author(s).)

Introduction: Chimeric antigen receptor T-cell (CAR T) therapies have transformed diffuse large B-cell lymphoma (DLBCL) treatment. It is important to better understand their use in Medicare Fee-for-Service (FFS) patients, who often differ from commercially insured populations in important ways., Methods: We analyzed Medicare FFS claims data, focusing on the utilization patterns across three CAR T products-lisocabtagene maraleucel (liso-cel), tisagenlecleucel (tisa-cel), and axicabtagene autoleucel (axi-cel)-which are indicated for the treatment of DLBCL. Our investigation covered the period from 2021 through 2022. This analysis spanned a 180-day period prior to CAR T procedure and extended to a 90-day post-CAR T. Utilization of healthcare services, healthcare spending, and comorbidities were assessed in the pre- and post-periods. Clinical trial and PPS-exempt center claims were removed from the analysis. Statistical comparisons between inpatient and outpatient cohorts were made using Wilcoxon's rank-sum tests for continuous variables and Chi-square tests or Fisher's exact tests for categorical variables., Results: Among the total 391 CAR T claims assessed, most of the CAR T therapies were administered in the inpatient setting (79%) compared to outpatient (21%). CAR T therapy in the inpatient setting received an average Medicare cost of US$498,723 ($276,138-$1,066,524), while the average Medicare cost for outpatient CAR T claims was $414,393 ($276,980-$849,878). There was a higher 3-month average post-period cost for those hospitals utilizing CAR T in the outpatient setting than the inpatient setting ($15,794 vs. $10,244). Despite the higher post-period cost, when looking at the CAR T procedure and pre- and post-periods as a single episode, beneficiaries receiving outpatient CAR T had less cost for the total episode of care ($587,908 vs. $529,188). Follow-up inpatient claims were also assessed post-CAR T procedure for 30 days. The rate of post-CAR T inpatient re-admission was significantly lower for beneficiaries receiving the index CAR T in the inpatient setting (21%) compared to outpatient CAR T (59%). Days between index CAR T discharge and IP admission were also significantly shorter for OP CAR T compared to IP CAR T (8.0 vs. 14.1 days, p < 0.0001). Additionally, IP CAR T had a longer ALOS on the admission claim (6.9 vs. 6.2 days)., Conclusion: CAR T therapy for the treatment of LBCL has become more common within the Medicare population, primarily in the inpatient setting. This study helps understand providers' cost and associated patient care around CAR T administration. The data show that the average cost received by hospitals encompasses the expenses related to both the CAR T drug and the medical services delivered to patients., (© 2024. The Author(s).)

Background: Management of complicated pleural infections (CPIs) had historically been surgical; however, following the publication of the second multicenter intrapleural sepsis trial (MIST-2), combination tissue plasminogen (tPA) and dornase (DNase) offers a less invasive and effective treatment. Our aim was to assess the quality of life (QOL) and functional ability of patients' recovery from a CPI managed with either intrapleural fibrinolytic therapy (IPFT) or surgery., Methods: We identified 565 patients managed for a CPI between January 1, 2013 and March 31, 2018. There were 460 patients eligible for contact, attempted through 2 phone calls and one mailer. Two questionnaires were administered: the Short Form 36-Item Health Survey (SF-36) and a functional ability questionnaire., Results: Contact was made in 35% (159/460) of patients, and 57% (90/159) completed the survey. Patients had lower QOL scores compared to average US citizens; those managed with surgery had higher scores in physical functioning (surgery: 80, IPFT: 70, P=0.040) but lower pain scores (surgery: 58, IPFT: 68, P=0.045). Of 52 patients who returned to work, 48% (25) reported an impact on their work effectiveness during recovery, similarly between management strategies (IPFT: 50%, 13/26 vs. surgery: 46%, 12/26; P=0.781)., Conclusion: Patients with a CPI had a lower QOL compared with average US citizens. Surgically managed patients reported improved physical functioning but worse pain compared with patients managed with IPFT. Patients returned to work within 4 weeks of discharge, and nearly half reported their ability to work effectively was impacted by their recovery. With further research into recovery timelines, patients may be appropriately counselled for expectations., Competing Interests: Disclosure: There is no conflict of interest or other disclosures., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Despite advances in cervical cancer (CC) prevention, detection, and treatment in the US, health disparities persist, disproportionately affecting underserved populations or regions. This study analyzes the geographical distribution of both CC and recurrent/metastatic CC (r/mCC) in the US and explores potential risk factors of higher disease burden to inform potential strategies to address disparities in CC and r/mCC., Methods: We estimated CC screening rates, as well as CC burden (number of patients with CC diagnosis per 100,000 eligible enrollees) and r/mCC burden (proportion of CC patients receiving systemic therapy not in conjunction with surgery or radiation), at the geographic level between 2017-2022 using administrative claims. Data on income and race/ethnicity were obtained from US Census Bureau's American Community Survey. Brachytherapy centers were proxies for guideline-conforming care for locally advanced CC. Associations among demographic, socioeconomic, and healthcare resource variables, with CC and r/mCC disease burden were assessed., Results: Between 2017-2022, approximately 48,000 CC-diagnosed patients were identified, and approximately 10,000 initiated systemic therapy treatment. Both CC and r/mCC burden varied considerably across the US. Higher screening was significantly associated with lower CC burden only in the South. Lower income level was significantly associated with lower screening rates, higher CC and r/mCC burden. Higher proportion of Hispanic population was also associated with higher CC burden. The presence of ≥1 brachytherapy center in a region was significantly associated with a reduction in r/mCC burden (2.7%)., Conclusion: CC and r/mCC disparities are an interplay of certain social determinants of health, behavior, and race/ethnicity. Our findings may inform targeted interventions for a geographic area, and further highlight the importance of guideline-conforming care to reduce disease burden., Competing Interests: Tara Castellano has received consulting fees from Glaxo-Smith-Klein; Andrew K. ElHabr and Ezgi Berksoy are paid employees of Value Analytics Labs, a healthcare consultancy company; Jie Ting and Yitong J. Zhang are employees and stack holders of Pfizer Inc.; Kathleen Moore has participated in data monitoring or advisory boards for Astra Zeneca, Aravive, Alkemeres, Aadi, Blueprint pharma, Clovis, Caris, Duality, Elevar, Eisai, EMD Serono, GSK/Tesaro, Genentech/Roche, Hengrui, Immunogen, Janssen, Lilly, Mersana, Merck, Myriad, Mereo, Novartis, OncXerna, Onconova, SQZ, Tarveda, VBL Therapeutics, Verastem and Zentalis, received support for attending meetings from Astra Zeneca, GSK/Tesaro, and BioNTech, and holds a leadership role with GOG partners; Leslie Randall reports personal fees from Seagen Inc. for an educational webinar at drug launch and speaker’s bureau and personal fees from Merck for an unbranded educational video for cervical cancer. Her institute receives research funding for clinical research from Seagen and Merck. She reports personal fees from BluPrint Oncology, PER, CurioScience, Projects in Knowledge, AstraZeneca, Tesaro, Merck, Mersana, Agenus, Rubius Therapeutics, Myriad Genetics, EMD Serono, Genentech/Roche, Seattle Genetics, Novartis, and Eisai, all outside the submitted work; Jagpreet Chhatwal and Turgay Ayer are co-owners of Value Analytics Labs; Charles A. Leath III has received consulting fees from Seagen Inc. for service on Scientific Advisory boards, cervical cancer research funding from Agenus, Rubius Therapeutics, and Seagen Inc., and funding from the NCI UG1 CA23330 and P50 CA098252; Fernanda Musa and Christina Washington have no competing interests to disclose., (Copyright: © 2024 Castellano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objective: Rehabilitation therapy plays an important role in treating physical and functional impairments observed in individuals undergoing hematopoietic stem cell transplants (HSCT). This study assessed the rehabilitation practices implemented in the HSCT population internationally., Materials and Methods: A 48-question online survey comprising questions soliciting information regarding patient characteristics, therapy details (timing, indication, and administering providers), outcome measures, and precautions were developed by an international group of cancer rehabilitation physicians. As reported by European registries, surveys were administered to personnel providing care to patients receiving HSCT at cancer centers, which comprised the top 10% of HSCT volume. In addition, emails were sent to National Medical Societies and registries in the Latin America, Asia, and Pacific regions., Results: Forty-three institutions from 18 countries responded to the survey. Half of the centers provided referrals for rehabilitation therapy at the time of admission. Referrals were provided for functional decline (84.5%), risk of falls (53.3%), and discharge planning (42.2%). Rehabilitation therapies were administered by physical therapists (93.0%), occupational therapists (34.9%), therapy aides (14.0%), and speech-language pathologists (11.6%). Approximately 95% of the surveyed centers used objective functional measures such as sit-to-stand (46.5%), grip strength (46.5%), and 6-min walk/gait speed (both 34.9%). The blood counts were monitored to determine the appropriateness of the therapy modalities., Conclusion: Rehabilitation practices varied internationally; however, most centers provided skilled therapy during hospitalization for HSCT, utilized objective and patient-reported outcomes, and monitored blood counts to determine the safety of administering therapy., (Copyright © 2024 Hematology/Oncology and Stem Cell Therapy.)

Background: Acute upper airway compromise is a rare but catastrophic complication after anterior cervical discectomy and fusion. This study aims to develop a score to identify patients at risk of acute postoperative airway compromise (PAC)., Methods: Potential risk factors for acute PAC were selected by a modified Delphi process. Ten patients with acute PAC were identified of 1466 patients who underwent elective anterior cervical discectomy and fusion between July 2014 and May 2019. A comparison group was created by a randomized selection process (non-PAC group). Factors associated with PAC and a P value of < 0.10 were entered into a logistic regression model and coefficients contributed to each risk factor's overall score. Calibration of the model was evaluated using the Hosmer-Lemeshow goodness-of-fit test. Quantitative discrimination was calculated, and the final model was internally validated with bootstrap sampling., Results: We identified 18 potential risk factors from our Delphi process, of which 6 factors demonstrated a significant association with airway compromise: age >65 years, current smoking status, American Society of Anesthesiologists class >2, history of a bleeding disorder, surgery of upper subaxial cervical spine (above C4), and duration of surgery >179 minutes. The final prediction model included 5 predictors with very strong performance characteristics. These 5 factors formed the PAC score, with a range from 0 to 100. A score of 20 yielded the greatest balance of sensitivity (80%) and specificity (88%)., Conclusions: The acute PAC score demonstrates strong performance characteristics. The PAC score might help identify patients at risk of upper airway compromise caused by surgical site abnormalities., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Deep learning-based mammographic evaluations could noninvasively assess response to breast cancer chemoprevention. We evaluated change in a convolutional neural network-based breast cancer risk model applied to mammograms among women enrolled in SWOG S0812, which randomly assigned 208 premenopausal high-risk women to receive oral vitamin D3 20 000 IU weekly or placebo for 12 months. We applied the convolutional neural network model to mammograms collected at baseline (n = 109), 12 months (n = 97), and 24 months (n = 67) and compared changes in convolutional neural network-based risk score between treatment groups. Change in convolutional neural network-based risk score was not statistically significantly different between vitamin D and placebo groups at 12 months (0.005 vs 0.002, P = .875) or at 24 months (0.020 vs 0.001, P = .563). The findings are consistent with the primary analysis of S0812, which did not demonstrate statistically significant changes in mammographic density with vitamin D supplementation compared with placebo. There is an ongoing need to evaluate biomarkers of response to novel breast cancer chemopreventive agents., (© The Author(s) 2024. Published by Oxford University Press.)

Purpose: Targeted Agent and Profiling Utilization Registry (TAPUR) is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with soft tissue sarcoma with cyclin-dependent kinase 4 ( CDK4 ) amplification treated with palbociclib are reported., Methods: Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0 to 2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration (SD16+) according to RECIST v1.1. The DC rate was estimated with a 90% CI. Secondary end points included OR, progression-free survival (PFS), overall survival (OS), duration of response, duration of SD, and safety., Results: Forty-two patients with CDK4 amplification were enrolled. One patient was not evaluable for efficacy. One patient with partial response and 18 with SD16+ were observed for DC and OR rates of 46% (90% CI, 36 to 100) and 2% (95% CI, <1 to 13), respectively. Median PFS was 16 weeks (95% CI, 9 to 28) and median OS was 69 weeks (95% CI, 31 to 111) for evaluable patients. Twenty patients had at least one grade 3 to 4 adverse event (AE) at least possibly related to palbociclib, including alanine aminotransferase increase, anemia, fatigue, hypophosphatemia, leukopenia, neutropenia, and thrombocytopenia. No serious AEs were reported., Conclusion: Palbociclib met prespecified criteria to declare a signal of antitumor activity in patients with sarcoma and CDK4 amplification.

There has been ongoing debate on the association between obesity and outcomes in acute myeloid leukemia (AML). Currently few studies have stratified outcomes by class I obesity, class II obesity, and class III obesity, and a more nuanced understanding is becoming increasingly important with the rising prevalence of obesity. We examined the association between body mass index (BMI) and outcomes in previously untreated AML in younger patients (age ≤60) enrolled in SWOG S1203 (n = 729). Class III obesity was associated with an increased rate of early death (p = 0.004) and worse overall survival (OS) in multivariate analysis (hazard ratio (HR) 2.48, 95% confidence interval (CI) 1.62-3.80 versus normal weight). Class III obesity was also associated with worse OS after allogeneic hematopoietic cell transplant (HR 2.37, 95% CI 1.24-4.54 versus normal weight). These findings highlight the unique risk of class III obesity in AML, and the importance of further investigation to better characterize this patient population., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Nintedanib is a small molecule tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR). The purpose of the study was to evaluate the response rate for patients with advanced non-small cell lung cancer (NSCLC) with mutations in TP53 , VEGFR1-3 , PDGFR-A , PDGFR-B , and FGFR1-3 treated with nintedanib as part of an open-label, single-arm pilot study., Methods: Patients with advanced NSCLC previously treated with platinum-doublet chemotherapy with the above mutations were enrolled. Exclusion criteria included necrotic tumors with invasion of blood vessels, history of recent thromboembolic events, increased risk of bleeding or thrombosis, myocardial infarction, and weight loss >10% within past 6 months. Nintedanib was administered at a dose of 200 mg orally twice daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Secondary endpoints included progression-free survival (PFS) and correlating outcomes with specific mutations. This study was registered with ClinicalTrials.gov, number NCT02299141., Results: Between 2015 and 2019, 20 patients were enrolled with a median age was 66 years, 15 (75%) were females, 15 (75%) had adenocarcinoma, and 17 patients had a TP53 mutation (85%). Seventeen (85%) had received prior immunotherapy and 11 (55%) had received at least three prior lines of systemic therapy. The ORR was 15% with three partial responses (PR), while 12 patients had stable disease (SD), with disease control rate (DCR) consisting of a PR and SD greater than or equal to 16 weeks of 65% (n=13). Median PFS was 4.3 months [95% confidence interval (CI): 1.8-7.9] and median overall survival (OS) was 11.3 months (95% CI: 3.5-44.2). Three patients experienced prolonged clinical benefit from nintedanib, remaining on treatment for over 1 year and all three had a TP53 mutation and received prior immunotherapy. The most common adverse events of any grade included nausea (80%), fatigue (70%), diarrhea (60%), and anorexia (60%)., Conclusions: In this pilot study in heavily pretreated and molecularly selected patients with metastatic NSCLC, nintedanib showed modest activity., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1717/coif). D.M. serves as an unpaid editorial board member of Journal of Thoracic Disease from October 2022 to September 2024. All authors report that the study was funded by the National Comprehensive Cancer Network (NCCN) Oncology Research program as an independent, investigator-initiated study supported through a grant from Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI) with funding supplied to the institution. S.D. reports an advisory role for AstraZeneca, Genentech, Merus and Jazz pharmaceuticals and royalties from Springer publications. D.M. reports research funding from Heat Biologics, Merck, Celgene, AstraZeneca, Baxter, Incyte, AbbVie, Bristol Myers Squibb, EpicentRx, Pfizer, Roche, Lilly, Altum Pharmaceuticals, Array BioPharma, Surface Oncology, Arcus Biosciences, Boehringer Ingelheim, Y-mAbs Therapeutics and serves in an advisory role for AbbVie, G1 Therapeutics, Lilly Medical, Miratic Therapeutics, Arcus Biosciences. S.N.W. reports research funding from SWOG-Clinical Trials Partnership, American Society of Hematology, AbbVie, Gilead, Immunomedics Inc., Daiichi Sankyo, Cullinan Pearl, Verastem Inc, Janssen Research and Development LLC, Elevation Oncology, Genentech, Verastem, Advenchen, Ribon, Loxo Oncology, Takeda, Hoffman-LaRoche, honoraria from ASCO, MJH Life Sciences, travel support from Gilead, and advisory roles for Janssen, Gilead, AstraZeneca, and Hoosier Cancer Research Network. The authors have no other conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Introduction: Pirtobrutinib, a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor, has demonstrated promising efficacy in B-cell malignancies and is associated with low rates of discontinuation and dose reduction. Pirtobrutinib is administered until disease progression or toxicity, necessitating an understanding of the safety profile in patients with extended treatment., Methods: Here we report the safety of pirtobrutinib in patients with relapsed/refractory B-cell malignancies with extended (≥12 months) drug exposure from the BRUIN trial. Assessments included median time-to-first-occurrence of adverse events (AEs), dose reductions, and discontinuations due to treatment-emergent AEs (TEAEs) and select AEs of interest (AESIs)., Results: Of 773 patients enrolled, 326 (42%) received treatment for ≥12 months. In the extended exposure cohort, the median time-on-treatment was 19 months. The most common all-cause TEAEs were fatigue (32%) and diarrhea (31%). TEAEs leading to dose reduction occurred in 23 (7%) and discontinuations in 11 (3%) extended exposure patients. One patient had a fatal treatment-related AE (COVID-19 pneumonia). Infections (73.0%) were the most common AESI with a median time-to-first-occurrence of 7.4 months. Majority of TEAEs and AESIs occurred during the first year of therapy., Conclusions: Pirtobrutinib therapy continues to demonstrate an excellent safety profile amenable to long-term administration without evidence of new or worsening toxicity signals., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objectives: The aim of this study was to evaluate if the previously reported improvements in lung cancer survival were consistent across age at diagnosis and by lung cancer subtypes., Materials and Methods: Data on lung cancers diagnosed between 1990 and 2016 in Denmark, Finland, Iceland, Norway and Sweden were obtained from the NORDCAN database. Flexible parametric models were used to estimate age-standardized and age-specific relative survival by sex, as well as reference-adjusted crude probabilities of death and life-years lost. Age-standardised survival was also estimated by the three major subtypes; adenocarcincoma, squamous cell and small-cell carcinoma., Results: Both 1- and 5-year relative survival improved continuously in all countries. The pattern of improvement was similar across age groups and by subtype. The largest improvements in survival were seen in Denmark, while improvements were comparatively smaller in Finland. In the most recent period, age-standardised estimates of 5-year relative survival ranged from 13% to 26% and the 5-year crude probability of death due to lung cancer ranged from 73% to 85%. Across all Nordic countries, survival decreased with age, and was lower in men and for small-cell carcinoma., Conclusion: Lung cancer survival has improved substantially since 1990, in both women and men and across age. The improvements were seen in all major subtypes. However, lung cancer survival remains poor, with three out of four patients dying from their lung cancer within five years of diagnosis., Competing Interests: Declaration of competing interest PCL received support from the Swedish Cancer Society and the Swedish Research Council for the submitted work. ML received support from the Swedish Cancer Society for the submitted work. ML owns stock in Pfizer and Astra Zeneca. The authors have no other relationships of activities that could appear to have influenced the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: The current staging system for esophageal adenocarcinoma only considers tumor grade in early tumors. The aim of this study was to evaluate the impact of tumor differentiation on response to neoadjuvant chemoradiotherapy and survival in patients with locally advanced esophageal adenocarcinoma., Methods: This was a multi-institution retrospective review of all patients with esophageal cancer who underwent neoadjuvant chemoradiotherapy followed by esophagectomy from January 2010 to December 2017. Response to neoadjuvant therapy and survival was compared between patients with well- or moderately differentiated (G1/2) tumors versus poorly differentiated (G3) tumors., Results: There were 550 patients, 485 men (88.2%) and 65 women. The median age was 61 years, and the tumor was G1/2 in 288 (52.4%) and G3 in 262 patients. Overall clinical stage before neoadjuvant therapy was similar between groups. Pathologic complete response (pCR) was found in 87 patients (15.8%). The frequency of pCR was similar between groups, but residual disease in the esophagus and lymph nodes was significantly more likely with G3 tumors. Median follow-up was 63 months and absolute survival, overall survival, and disease-free survival were all significantly worse in patients with G3 tumors. Further, even with pCR, patients with G3 tumors had significantly worse survival., Conclusions: This study showed that response to neoadjuvant therapy was not affected by tumor differentiation. However, poor differentiation was associated with worse survival compared with patients with G1/2 tumors, even among those with pCR. These results suggest that poor differentiation should be considered as an added risk factor for clinical staging in patients with locally advanced esophageal adenocarcinoma., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: The progression of ductal carcinoma in situ (DCIS) to invasive breast carcinoma (IBC) in humans is highly variable. To better understand the relationship between them, we performed a multi-omic characterization of co-occurring DCIS and IBC lesions in a cohort of individuals., Methods: Formalin-fixed paraffin-embedded tissue samples from 50 patients with co-occurring DCIS and IBC lesions were subjected to DNA-seq and whole transcriptome RNA-seq. Paired DCIS and IBC multi-omics profiles were then interrogated for DNA mutations, gene expression profiles and pathway analysis., Results: Most small variants and copy number variations were shared between co-occurring DCIS and IBC lesions, with IBC exhibiting on average a higher degree of additional mutations. However, 36% of co-occurring lesions shared no common mutations and 49% shared no common copy number variations. The most frequent genomic variants in both DCIS and IBC were PIK3CA, TP53, KMT2C, MAP3K1, GATA3 and SF3B1, with KMT2C being more frequent in DCIS and TP53 and MAP3K1 more frequent in IBC, though the numbers are too small for definitive conclusions. The most frequent copy number variations were seen in MCL1, CKSB1 and ERBB2. ERBB2 changes were not seen in IBC unless present in the corresponding DCIS. Transcriptional profiles were highly distinct between DCIS and IBC, with DCIS exhibiting upregulation of immune-related signatures, while IBC showed significant overexpression in genes and pathways associated with cell division and proliferation. Interestingly, DCIS and IBC exhibited significant differential expression of different components of extracellular matrix (ECM) formation and regulation, with DCIS showing overexpression of ECM-membrane interaction components while IBC showed upregulation of genes associated with fibronectin and invadopodia., Conclusion: While most co-occurring DCIS and IBC were mutationally similar and suggestive of a common clonal progenitor, transcriptionally the lesions are highly distinct, with IBC expressing key pathways that facilitate invasion and proliferation. These results are suggestive of additional levels of regulation, epigenetic or other, that facilitate the acquisition of invasive properties during tumor evolution., (© 2024. The Author(s).)

Highlighting here a patient case with neuroblastoma, renal cancer & GIST from germline SDHA.

Purpose: Standard-of-care for HER2-positive metastatic breast cancer (HER2 + mBC) patients consists of trastuzumab ± pertuzumab with chemotherapy in first-line (1L), and ado-trastuzumab emtansine (T-DM1) or the more recently approved trastuzumab deruxtecan (T-DXd) in second-line (2L). Contemporary data on treatment sequencing and real-world effectiveness is limited. This study aims to report 2L treatments and outcomes among HER2 + mBC patients in the United States (US)., Methods: HER2 + mBC patients initiating 2L treatment (index date) between January 2014 and February 2021 were identified from the Syapse Learning Health Network (LHN) database. Summary statistics for patient characteristics, treatment received, reasons for 2L discontinuation and time to 2L-clinical outcomes are reported., Results: Of the 312 patients initiating 2L treatment, had a median age of 59 years (interquartile range [IQR], 50-66) at the start of 2L. The majority were white (69%) and had de novo mBC (62%). Top three 2L regimens included T-DM1 ± endocrine therapy (29%), trastuzumab/pertuzumab/taxane (10%) and T-DM1/trastuzumab (8%). Around 88% discontinued 2L and 63% received subsequent treatment. Median time-to-next-treatment was 10.6 months (95% CI, 8.8-13.3) and real-world progression-free-survival was 7.9 months (95% CI, 7.0-9.9). Among 274 patients who discontinued 2L, 47% discontinued due to progression and 17% because of intolerance/toxicity, respectively., Conclusion: This real-world US study showed that approximately two-thirds of 2L patients received subsequent therapy and disease progression was the most common reason for 2L discontinuation highlighting the need for timely 2L treatment with the most efficacious drug to allow patients to achieve longer treatment duration and delayed progression., (© 2024. The Author(s).)

Virion-mediated outbreaks are imminent and despite rapid responses, continue to cause adverse symptoms and death. Therefore, tunable, sensitive, high-throughput assays are needed to help diagnose future virion-mediated outbreaks. Herein, it is developed a tunable in situ assay to selectively enrich virions and extracellular vesicles (EVs) and simultaneously detect antigens and nucleic acids at a single-particle resolution. The Biochip Antigen and RNA Assay (BARA) enhanced sensitivities compared to quantitative reverse-transcription polymerase chain reaction (qRT-PCR), enabling the detection of virions in asymptomatic patients, genetic mutations in single virions, and enabling the continued long-term expression of viral RNA in the EV-enriched subpopulation in the plasma of patients with post-acute sequelae of the coronavirus disease of 2019 (COVID-19). BARA revealed highly accurate diagnoses of COVID-19 by simultaneously detecting the spike glycoprotein and nucleocapsid-encoding RNA in saliva and nasopharyngeal swab samples. Altogether, the single-particle detection of antigens and viral RNA provides a tunable framework for the diagnosis, monitoring, and mutation screening of current and future outbreaks., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Background and Purpose: Stage at cancer diagnosis is an important predictor of cancer survival. TNM stage is constructed for anatomic solid cancer diagnoses from tumor size (T), nodal spread (N) and distant metastasis (M) and categorized in groups 0-I, II, II and IV. TNM stage is imperative in cancer diagnosis, management and control, and of high value in cancer surveillance, for example, monitoring of stage distributions. This study yields an overview of TNM availability and trends in stage distribution in the Nordic countries for future use in monitoring and epidemiologic studies., Material and Methods: TNM information was acquired from the cancer registries in Denmark, Norway, Sweden, and Iceland during 2004-2016 for 26 cancer sites in the three former countries and four in Iceland. We studied availability, comparability, and distribution of TNM stage in three periods: 2004-2008, 2009-2013, and 2014-2016, applying a previously validated algorithm of 'N0M0 for NXMX'. For cancers of colon, rectum, lung, breast, and kidney, we examined TNM stage-specific 1-year relative survival to evaluate the quality in registration of TNM between countries., Results: Denmark, Sweden, and Iceland exhibited available TNM stage proportions of 75-95% while proportions were lower in Norway. Proportions increased in Sweden over time but decreased in Denmark. One-year relative survival differed substantially more between TNM stages than between countries emphasizing that TNM stage is an important predictor for survival and that stage recording is performed similarly in the Nordic countries., Interpretation: Assessment and registration of TNM stage is an imperative tool in evaluations of trends in cancer survival between the Nordic countries.

Background: The survival in patients diagnosed with cutaneous malignant melanoma (CMM) has improved in the Nordic countries in the last decades. It is of interest to know if these improvements are observed in all ages and for both women and men., Methods: Patients diagnosed with CMM in the Nordic countries in 1990-2016 were identified in the NORDCAN database. Flexible parametric relative survival models were fitted, except for Iceland where a non-parametric Pohar-Perme approach was used. A range of survival metrics were estimated by sex, both age-standardised and age-specific., Results: The 5-year relative survival improved in all countries, in both women and men and across age. While the improvement was more pronounced in men, women still had a higher survival at the end of the study period. The survival was generally high, with age-standardised estimates of 5-year relative survival towards the end of the study period ranging from 85% in Icelandic men to 95% in Danish women. The age-standardised and reference-adjusted 5-year crude probability of death due to CMM ranged from 5% in Danish and Swedish women to 13% in Icelandic men., Conclusion: Although survival following CMM was relatively high in the Nordic countries in 1990, continued improvements in survival were observed throughout the study period in both women and men and across age., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The combination of the phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor zandelisib with the Bruton's tyrosine kinase (BTK) inhibitor zanubrutinib was hypothesized to be synergistic and prevent resistance to single-agent therapy. This phase 1 study (NCT02914938) included a dose-finding stage in patients with relapsed/refractory (R/R) B-cell malignancies (n = 20) and disease-specific expansion cohorts in follicular lymphoma (FL; n = 31) or mantle cell lymphoma (MCL; n = 19). The recommended phase 2 dose was zandelisib 60 mg on Days 1-7 plus zanubrutinib 80 mg twice daily continuously in 28-day cycle. In the total population, the most common adverse events (AEs; all grades/grade 3-4) were neutropenia (35%/24%), diarrhoea (33%/2%), thrombocytopenia (32%/8%), anaemia (27%/8%), increased creatinine (25%/0%), contusion (21%/0%), fatigue (21%/2%), nausea (21%/2%) and increased aspartate aminotransferase (24%/6%). Three patients discontinued due to AEs. The overall response rate was 87% (complete response [CR] = 33%) for FL and 74% (CR = 47%) for MCL. The median duration of response and progression-free survival (PFS) were not reached in either group. The estimated 1-year PFS was 72.3% (95% confidence interval [CI], 51.9-85.1) for FL and 56.3% (95% CI, 28.9-76.7) for MCL (median follow-up: 16.5 and 10.9 months respectively). Zandelisib plus zanubrutinib was associated with high response rates and no increased toxicity compared to either agent alone., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Abstract: Bispecific antibodies (BsAb) that target CD3 and CD20 represent a new milestone in the treatment of patients with B-cell non-Hodgkin lymphoma. These drugs have demonstrated remarkable single-agent activity in patients with heavily pretreated disease, and 3 drugs have so far received regulatory approvals in various countries. However, BsAbs can potentially lead to severe toxicity associated with T-cell activation, particularly cytokine release syndrome (CRS). The anticipated widespread use of these off-the-shelf products poses challenges for implementation and highlights the need for guidance in anticipating, mitigating, and managing adverse events. In clinical trials, guidance for the evaluation and treatment of CRS and neurotoxicity associated with BsAb therapy has been modeled after algorithms originally created for chimeric antigen receptor (CAR) T-cell therapies and other immune effector therapies, yet notable differences in timing, quality, and severity exist between the toxicities of BsAbs and CAR T-cell therapies. We therefore convened an international panel of academic and community practice physicians, advanced practitioners, registered nurses, and pharmacists with experience using CD3×CD20 BsAbs in clinical trial and off-trial settings to provide comprehensive, consensus-based recommendations specific to the assessment and management of CD3×CD20 BsAb-related toxicities., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Since the early 2000s, overall and site-specific cancer survival have improved substantially in the Nordic countries. We evaluated whether the improvements have been similar across countries, major cancer types, and age groups., Material and Methods: Using population-based data from the five Nordic cancer registries recorded in the NORDCAN database, we included a cohort of 1,525,854 men and 1,378,470 women diagnosed with cancer (except non-melanoma skin cancer) during 2002-2021, and followed for death until 2021. We estimated 5-year relative survival (RS) in 5-year calendar periods, and percentage points (pp) differences in 5-year RS from 2002-2006 until 2017-2021. Separate analyses were performed for eight cancer sites (i.e. colorectum, pancreas, lung, breast, cervix uteri, kidney, prostate, and melanoma of skin)., Results: Five-year RS improved across nearly all cancer sites in all countries (except Iceland), with absolute differences across age groups ranging from 1 to 21 pp (all cancer sites), 2 to 20 pp (colorectum), -1 to 36 pp (pancreas), 2 to 28 pp (lung), 0 to 9 pp (breast), -11 to 26 pp (cervix uteri), 2 to 44 pp (kidney), -2 to 23 pp (prostate) and -3 to 30 pp (skin melanoma). The oldest patients (80-89 years) exhibited lower survival across all countries and sites, although with varying improvements over time., Interpretation: Nordic cancer patients have generally experienced substantial improvements in cancer survival during the last two decades, including major cancer sites and age groups. Although survival has improved over time, older patients remain at a lower cancer survival compared to younger patients.

Aim: Same day discharge (SDD) for colorectal surgery shows increasing promise in the era of enhanced recovery after surgery protocols and minimally invasive surgery. It has become increasingly relevant due to the constraints posed by the COVID-19 pandemic. The aim of this study was to compare SDD and postoperative day 1 (POD1) discharge to understand the clinical outcomes and financial impact on factors such as cost, charge, revenue, contribution margin and readmission., Method: A retrospective review of colectomies was performed at a single institution over a 2-year period (n = 143). Two populations were identified: SDD (n = 51) and POD1 (n = 92). Patients were selected by International Statistical Classification of Diseases and Related Health Problems-10 (ICD-10) and Diagnosis Related Grouper (DRG) codes., Results: There was a statistically significant difference favouring SDD in total hospital cost (p < 0.0001), average direct costs (p < 0.0001) and average charges (p < 0.0016). SDD average hospital costs were $8699 (values in USD throughout) compared with $11 652 for POD 1 (p < 0.0001), and average SDD hospital charges were $85 506 compared with $97 008 for POD1 (p < 0.0016). The net revenue for SDD was $22 319 while for POD1 it was $26 173 (p = 0.14). Upon comparison of contribution margins (SDD $13 620 vs. POD1 $14 522), the difference was not statistically significant (p = 0.73). There were no identified statistically significant differences in operating room time, robotic console time, readmission rates or surgical complications., Conclusions: Amidst the pandemic-related constraints, we found that SDD was associated with lower hospital costs and comparable contribution margins compared with POD1. Additionally, the study was unable to identify any significant difference between operating time, readmissions, and surgical complications when performing SDD., (© 2024 Association of Coloproctology of Great Britain and Ireland.)

Importance: Angiosarcoma is an aggressive vascular malignant neoplasm presenting either as a primary or secondary cancer, often arising after radiotherapy or in the context of preexisting lymphedema. Comprehensive data describing its incidence and presentation patterns are needed., Objective: To describe the incidence, presenting characteristics, and change over time of angiosarcoma in the US., Design, Setting, and Participants: This retrospective cross-sectional study used data from the US Cancer Statistics (USCS) National Program of Cancer Registries-Surveillance, Epidemiology, and End Results Combined Database, which captures more than 99% of newly diagnosed cancers in the US. The study included all 19 289 patients in the US with a new diagnosis of angiosarcoma between 2001 and 2020 captured in the USCS database. Statistical analysis was performed from June to September 2023., Main Outcomes and Measures: Incidence of angiosarcoma, demographics of patients with angiosarcoma, and extent of disease at presentation., Results: The study included 19 289 patients (median age, 71 years [IQR, 59-80 years]; 10 506 women [54.5%]) with a new diagnosis of angiosarcoma. The US incidence of angiosarcoma doubled between 2001 (657 cases) and 2019 (1312 cases), reflecting both an increase in the adjusted incidence rate of 1.6% per year (P = .001), to 3.3 cases per 1 000 000 person-years (95% CI, 3.1-3.5 cases per 1 000 000 person-years), and an increase in the population at risk. In 2020, the reported incidence rate (3.0 cases per 1 000 000 person-years) and cases of angiosarcoma (n = 1159) were modestly lower than in 2019. Overall, 72.3% of cases of angiosarcoma (n = 13 955) were cutaneous, subcutaneous, or breast angiosarcomas; 24.4% were visceral (n = 4701); and 3.3% were located in unknown or rare primary sites (n = 633). Secondary breast and chest wall angiosarcomas among women represented the largest contribution to increasing incidence. Among breast angiosarcomas, 99.2% (2684 of 2705) were in women and 71.9% (1944 of 2705) were secondary. A total of 80.4% of chest wall or thorax cases among women (1861 of 2316) were secondary vs 26.5% among men (112 of 422), and 63.9% of upper extremity cases among women (205 of 321) were secondary vs 26.8% (56 of 209) among men (P = .001). Rates of secondary angiosarcoma in the abdomen and lower extremities were similar between men and women. The incidence rate of visceral angiosarcoma was also found to be increasing (1.5% per year; P = .001)., Conclusions and Relevance: This cross-sectional study describes angiosarcoma presentation patterns and incidence rates in the US over a 20-year period and shows that the number of cases in men and women increased, with the greatest increase among women with secondary angiosarcoma of the chest, breast, and upper extremity. These data increase awareness of a rare but highly morbid disease and highlight the need for improved early detection of angiosarcoma among patients at high risk, such as women with a history of breast cancer.

Background: Rehabilitation therapy is important to treat physical and functional impairments that may occur in individuals receiving physically taxing, yet potentially curative hematopoietic stem cell transplants (HSCT). However, there is scarce data on how rehabilitation is delivered during HSCT in real-life setting. Our objective is to assess the rehabilitation practices for adult patients hospitalized for HSCT in the United States., Methods: A 48-question online survey with cancer centers with the top 10% HSCT volumes (per American registries). We obtained data on patient characteristics, rehabilitation therapy details (timing, indication, administering providers), physical function objective and subjective outcome measures, and therapy activity precautions., Results: Fourteen (out of 21) institutions were included. Rehabilitation therapy referrals occurred at admission for all patients at 35.7% of the centers for: functional decline (92.9%), fall risk (71.4%), and discharge planning (71.4%). Participating institutions had physical therapists (92.9%), occupational therapists (85.7%), speech language pathologists (64.3%) and therapy aides (35.7%) in their rehabilitation team. Approximately 71% of centers used objective functional measures including sit-to-stand tests (50.0%), balance measures (42.9%), and six-minute walk/gait speed (both 35.7%). Monitoring of blood counts to determine therapy modalities frequently occurred and therapies held for low platelet or hemoglobin values; but absolute neutrophil values were not a barrier to participate in resistance or aerobic therapies (42.9%)., Discussion: Rehabilitation practices during HSCT varied among the largest volume cancer centers in the United States, but most centers provided skilled therapy, utilized objective, clinician and patient reported outcomes, and monitored blood counts for safety of therapy administration.