tbuckley/cabot-search huggingface dataset:
Digital health program for patients with cancer to support self-management: A retrospective real-world analysis.
Authors: Olof K. Bjarnadottir, Bartosz Dobies, Ari Páll Ísberg, Alice Jean White, Sigríður Svala Jónasdóttir, Saemundur Oddsson
Journal: Journal of Clinical Oncology (2024)

1570 Background: Sidekick Health’s 13-week digital health program was built to support cancer self-management. It was available free of charge to US-based cancer patients through commercial health insurance. The program includes disease education, mindfulness, medication adherence support, and asynchronous messaging with a care manager. We hypothesized that highly engaged users had reduced symptom frequency and severity, and improved quality of life (QoL) outcomes. Methods: In-app data were analyzed for registrations Aug 2021-Jan 2024: n(registered)=1286; n(retained ≥7 days)=795; n(QoL/symptoms)=284. QoL was defined as self-reported sleep quality, energy and stress (10-point scale, ≤4x/week). Symptoms were also self-reported (10-point scale, ≤7x/week). Generalized linear mixed models for repeated measures were used to investigate QoL, symptom frequency and severity changes over the program. Subgroup analysis: weekly iterative k-means clustering into highly- and less-engaged (based on total active days) to mitigate survival bias. Results: Diverse patients from 37 states engaged: mean age 58.0 years (SD=10.5), 71% female; 49% diagnosed &lt;6 months ago, 36% ≥12 months ago; 23% early-stage disease, 26% stable disease, 6% in remission and 2% terminal; 60% received chemotherapy, 24% radiation therapy, and 21% immunotherapy. Most (61%) registered users were active after 7 days and 29% after 90 days. Less-engaged users reported higher mean baseline weight (85.3kg (SD=26.7)) vs highly engaged (76.9kg (SD=18.3); p=0.010) but were otherwise similar (age, gender, height, time since diagnosis and treatment: p&gt;0.05). For QoL, highly engaged users had improved energy (p=0.013) and sleep (p=0.002), but not stress (p=0.164) vs less engaged. A significant time-group interaction for sleep (p&lt;0.001) showed highly engaged users had better sleep, and larger improvements over time vs less-engaged. Overall, users reported fewer symptoms over the program (IRR (95% CI)=0.965 (0.953, 0.978), p&lt;0.001). Symptom frequency decreased significantly for stress (p=0.034) and nausea (p=0.003), but not numbness (p=0.320) or fatigue (p=0.530). Highly engaged users’ symptom severity had a downward trajectory, compared with less-engaged, for fatigue (p=0.044) and nausea (p=0.001), but not stress (p=0.234) or numbness (p=0.680). Conclusions: Theprogram was accessed by a broad patient group and retention was high. Highly engaged users reported improved QoL (energy, sleep) and reduced symptom severity (fatigue, nausea). Total symptom frequency was reduced over the program, as well as for stress and nausea specifically. These findings indicate digital self-management is not only achievable for patients with cancer, but that higher engagement may improve patient-reported outcomes.
Use of IL-3RB to mediate antitumor effect of CAR-T cells through the JAK-STAT signaling pathway.
Authors: Qizhi Ma, Pei Shu, Fuchun Guo, Ning Liu, Yongmei Bai, Benxia Zhang, Yue Chen, Yongsheng Wang
Journal: Journal of Clinical Oncology (2024)

2541 Background: The application of CAR-T in solid tumors has not yet demonstrated significant clinical benefits. The continuous proliferation and decreased terminal differentiation of CAR-T cells in vivo are considered potential strategies that could alter this predicament. Cytokines, as the 3rd signal for T-cell activation, play a crucial role in the lifecycle and fate of T cells. In this study, we innovatively incorporated the IL-3 receptor β chain (IL-3RB) into the CAR structure to enhance signal transduction, potentially activating the anti-tumor function of CAR-T and maintaining the persistent proliferative activity. Methods: Transcriptional profiling analysis performed on HER2 or VEGFR1 CAR-T cells, with a specific focus on the gp140 cytokine family (IL-3/IL-5/CSF-2) and the receptor expression, validated by ELISA and Western blot. By cloning CAR genes containing different structural domains of the IL-3RB into the lentiviral vector pWPXLd, CAR expression, activation, depletion, proliferation, cytotoxicity, pSTAT3 and pSTAT5, and cytokine release of CAR-T cells were assessed using flow cytometry (FCM), Western blot (WB), RTCA, CCK-8, and ELISA. Subcutaneous/abdominal injections of SKOV3 cells or SKOV3-Luc cells into NSG mice, followed treated by CAR-T cells. Tumor burden was regularly monitored, and FCM and Q-PCR were utilized to assess the quantity and phenotype of CAR-T cells in vivo. Results: RNA-sequence, ELISA and WB revealed that upon activation of CAR-T cells, the expression of genes such as IL-3/IL-5/CSF-2 rapidly increased. However, their receptors were hardly expressed. IL-3RB modification did not affect the phenotype of resting CAR-T cells. But, co-cultured with target cells, IL-3RB significantly enhanced the anti-tumor effects of CAR-T cells. This was manifested by more rapid activation, promotion of persistent proliferation, delayed exhaustion phenotype, secretion of higher levels of cytokines (IL-2, IFN-γ, TNF-α) and efficient cytotoxicity. IL-3RB-expressing CAR-T cells exhibited activation of the JAK kinase and STAT3, STAT5 transcription factor signaling pathways in vitro. We established solid tumor models of subcutaneous (SKOV3) and intraperitoneal metastasis, where HER2/VEGFR1 CAR-T cells partially inhibited tumor cell growth in vivo. In contrast, IL-3RB-enhanced CAR-T cells completely eradicated tumor cells, and even achieving a state of complete remission. FCM and Q-PCR also confirmed that IL-3RB significantly improved the proliferation and survival of CAR-T cells in vivo. Conclusions: IL-3RB is scarcely expressed in T cells and not regulated by T cell activation. IL-3RB-modified CAR-T cells exhibit superior persistence and significant anti-tumor advantages in a solid tumor through the JAK-STAT signaling pathway. Our innovative CAR structure design has the potential to demonstrate promising anti-tumor effects in clinical translational applications.
Cost-utility of geriatric assessment (GA) in older adults with cancer: A model-based economic evaluation of four randomized controlled trials (RCTs).
Authors: Selai Akseer, Shant Yeretzian, Yeva Sahakyan, Lusine Abrahamyan, Martine Puts, Shabbir M.H. Alibhai
Journal: Journal of Clinical Oncology (2024)

1509 Background: Geriatric assessment (GA) is a guideline-recommended approach to optimize cancer management in older adults undergoing chemotherapy. Our recent cost-utility analysis of the published 5C (Clinical and Cost-effectiveness of a Comprehensive geriatric assessment and management for Canadian elders with Cancer) RCT comparing GA and management (GAM) with usual care in older adults with cancer did not demonstrate cost-effectiveness overall. However, the trial was limited by &lt;5% of study participants receiving GA prior to starting treatment. Three other GAM RCTs (GAIN, GAP-70, and INTEGERATE) have recently been published with evidence of efficacy on clinically relevant endpoints. Whether these are more cost effective than 5C is unclear. We evaluated the cost-effectiveness of GAM versus usual care in older adults with cancer using a decision model under a range of plausible scenarios representing the 4 trials. Methods: We performed cost-effectiveness analyses using the healthcare payer perspective and a 12-month time horizon. We incorporated Canadian costs and utility data from 5C, and used intervention details and effectiveness data from the three RCTs. We reported healthcare costs per quality-adjusted life year (QALY) and the incremental net monetary benefit (INMB) using a $50,000 per QALY threshold. In scenario analyses we examined the main cost drivers. Results: Across trials, the average QALY per patient ranged 0.577–0.662 for GA and 0.606–0.665 for UC, and the average total costs $31,234–$39,432 for GA and $29,261–$41,756 for UC. Chemotherapy expenses accounted for 46%-66% of total costs across trials. The INTEGERATE trial had a positive INMB of $6,074. The GAIN and GAP-70 trials had negative INMB value of -$2,123 and -$1,172, respectively. In comparison, in 5C, the total costs were $39,812 and $37,450 for GAM and UC, respectively, and QALYs were 0.728 and 0.751, respectively; the INMB was $-2,713. Conclusions: Trial results and the associated model of care from INTEGERATE suggested a positive net monetary benefit, primarily driven by reduced hospitalization. Evaluation of cost-effectiveness under a range of plausible scenarios from RCTs can provide important insights about GAM. Our results add to the growing data supporting the need to implement GAM in older adults with cancer starting chemotherapy and argue for its cost effectiveness under specific scenarios. Future trials should include hospitalization outcomes. Future economic analyses need to accurately capture chemotherapy costs.
Efficacy and safety of immune checkpoint inhibitors in recurrent or metastatic nasopharyngeal carcinoma: A systematic review and meta-analysis.
Authors: Luis Felipe Leite da Silva, Maria Luísa Siegloch Barros, Raul Vinícius da Silva, Farley Reis Rodrigues, Maysa Vilbert
Journal: Journal of Clinical Oncology (2024)

e14612 Background: Treatment options for recurrent or metastatic nasopharyngeal carcinoma (NPC) are limited. Recently, the introduction of Immune Checkpoint Inhibitors (ICIs), either as single agents or combined with other treatment options, has emerged as a potential treatment for NPC. Hence, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of ICIs compared to standard chemotherapy. Methods: We systematically searched PubMed, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) comparing ICIs versus standard chemotherapy in patients with NPC. The main outcomes were progression-free survival (PFS), overall survival (OS) and adverse events rate. All analyses used a random-effects model, with 95% confidence intervals (CIs) and were conducted on Review Manager 5.4. Results: A total of 1,188 patients from 5 RCTs were included, of which 634 (53.3%) received PD-1 inhibitors. In a pooled analysis of all studies, treatment with ICIs demonstrated a statistically significant benefit in OS (HR 0.73; 95% CI 0.61-0.87; p&lt;0.01). In trials evaluating ICI monotherapy versus chemotherapy (617 patients), PFS was not significantly different between groups (p=0.91). However, pooling two studies evaluating ICI combined with chemotherapy vs. chemotherapy (541 patients) demonstrated higher PFS for the ICI group (HR 0.53; 95% CI 0.42-0.67; p&lt;0.01). Overall pooled PFS was non-significant (HR 0.75; 95% CI 0.49-1.16; p=0.20). In all subgroup analyses, patients treated with ICI achieved greater PFS than chemotherapy: low EBV DNA level (HR 0.61; 95% CI 0.42-0.87; p=0.007) or high EBV DNA level (HR 0.44; 95% CI 0.35-0.56; p&lt;0.01), without liver metastasis (HR 0.68; 95% CI 0.47-0.98; p=0.04), and with liver metastasis (HR 0.56; 95% CI 0.38-0.83; p=0.04). Moreover, ICIs were well tolerated and not associated with an increased risk of serious adverse events (HR 0.96; 95% CI 0.82-1.11; p=0.56). The frequency of hypothyroidism increased in the ICI group (HR 2.07; 95% CI 1.63-2.63; p&lt;0.01). Other adverse events had similar rates in both groups, such as AST and ALT levels, diarrhea, pruritus, rash, stomatitis, and vomiting. Conclusions: This meta-analysis demonstrated that immune checkpoint inhibitors significantly enhanced overall survival without substantially increasing serious adverse events in patients with M/R NPC. Further studies are needed to identify the patients who benefit the most from ICI monotherapy or combination therapies. [Table: see text]
Symptoms reported by patients using an ePRO compared with those reported to nurses via telephone triage.
Authors: Michael A. Kolodziej, Mustafa S. Ascha, Andrew Frank, Chantel Hopper, Sibel Blau, Eric S. Schaefer, Bijoy Telivala, Lavi Kwiatkowsky
Journal: Journal of Clinical Oncology (2024)

1542 Background: It is unclear how symptoms reported by an electronic patient-reported outcomes (ePRO) tool compare to symptoms reported to triage nurses by patient-initiated telephone calls. This work describes symptoms reported using each of these methods, and the percent of patients requiring an acute office visit triggered by these symptom reports. Methods: Among patients diagnosed with breast, lung, or colon cancer at three community oncology practices from 2020 to 2023, we examined ePRO symptom reports and compared these with symptoms reported via telephone triage to nurses by patients not using the ePRO tool. Results: 3,509 patients reported symptoms by ePROs, and 9,071 patients only reported by phone. Among patients reporting by ePRO, 2,162 submitted both ePROs and used telephone triage services. The most common symptoms that patients reported by ePRO reports (47,284 reports) were weakness / fatigue (72.9% of patients), pain (62.0%), nausea (39.2%), and headache (33.1%). The most common symptoms that patients reported by phone reports (19,344 reports) were pain (32.9%), weakness / fatigue (13.4%), swelling (11.1%), cough (10.3%), and diarrhea (9.4%). The median number of reports in the ePRO group was 6.0 (mean 13.5, IQR: 2.0, 15.0) per patient and the median number of reports in the phone triage group was 1.0 (mean 2.1, IQR: 1.0, 2.0) per patient. The most common high-urgency symptoms in the ePRO group (defined by practice defined symptom threshold) were weakness / fatigue (67.2% of patients), pain (55.7%), headache (40.2%), nausea (32.0%), and difficulty breathing (29.2%), while the most common high-urgency symptoms (as determined by the triage nurse) in the phone triage group were pain (32.4%), weakness / fatigue (11.8%), swelling (11.4%), fever/chills (10.1%), and cough (9.7%). More patients reported high-urgency symptoms by ePRO (n = 1,873, 53.4%) compared to those reported by phone triage (n = 2,448, 27.0%). Of patients in the ePRO group with a severe symptom who visited a site with acute care visits data, 330 patients (45.4%) had an acute care visit within 72 hours of a symptom report compared to 745 patients (47.5%) in the telephone triage group. Conclusions: Patients using ePROs reported more symptoms than patients reporting by phone, possibly because electronic reporting allows patients to easily communicate symptoms to care providers and receive prompt attention. Pain and weakness/fatigue were the most common urgent symptoms in both groups. The need for an acute care visit was the same in both groups. Further refinement of the ePRO tool including standardization of symptom thresholds, more uniform implementation in practices, and patient education with respect to optimal use of the ePRO may enable practices to replace telephone triage with ePROs.
Assessing the environmental and downstream human health impacts of decentralizing cancer care.
Authors: Andrew Hantel, Colin Cernik, Thomas Walsh, Hajime Uno, Dalia Larios, Jonathan Slutzman, Gregory A. Abel
Journal: Journal of Clinical Oncology (2024)

1522 Background: Greenhouse gas emissions from healthcare are substantial and harm persons with cancer. Emissions from outpatient cancer care visits are not well described, nor are the downstream reduction in human harms that could be obtained through visit “decentralization” (telemedicine and local care when possible). Methods: This life-cycle assessment (LCA)-based study evaluated changes in emissions and downstream health harms associated with (1) telemedicine visits using retrospective observational analysis and (2) fully decentralized visits using counterfactual modeling. The retrospective observational cohort included persons receiving cancer care at Dana-Farber Cancer Institute (DFCI) and 20 affiliated facilities between 5/2015-12/2020. The main outcome was the adjusted per visit-day difference in emissions (in kilograms carbon dioxide equivalents: kgCO 2 e) between two periods: an in-person care period (5/2015-2/2020; “Pre”) and a telemedicine period (3/2020-12/2020; “Post”). Mixed effects log-linear model assessed emissions changes adjusted for age, sex, race, ethnicity, and cancer type, with random effects on person. The counterfactual model assessed emissions changes between actual in-person visits during the Pre period and a counterfactual with maximal decentralization. Visit-day eligibility for decentralization was obtained by categorizing appointments (e.g., clinician visit, infusion) as DFCI required, local care possible, or telemedicine possible. This cohort was matched to a national population diagnosed with cancer over the same period (Cancer in North America [CiNA] dataset) using mixed-effects linear modeling, through which annual changes in disability-adjusted life-years (DALY) from clinician visit decentralization were estimated using Eckelman’s mortality cost of carbon conversion. Results: There were123,890 unique patients in the DFCI cohort seen over 1.6 million visit-days (Pre N=110,180, Post N=61,691) at a median of 6 visit-days per patient (IQR 2, 15). An estimated 72,554,006 kgCO 2 e were within scope of the LCA emitted during the study period. In mixed-effects log-linear regression, the adjusted mean absolute reduction in per visit-day emissions between Pre and Post periods was 36.4 kgCO 2 e (95%CI 36.2,36.6), or a reduction of 81.3% (95%CI 80.8,81.7) compared to the baseline model. In the counterfactual decentralized care model of the Pre period, there was a relative emissions reduction of 33.1% (95%CI 32.9,33.3). When demographically matched to 10.3 million persons in the CiNA dataset, decentralized care would have reduced national emissions by 75.3 million kgCO 2 e annually; this corresponds to an estimated annual reduction of 15.0-47.7 DALYs. Conclusions: Employing decentralization through telemedicine and local care can substantially reduce emissions during cancer care delivery; this corresponds to a small reduction in human mortality.
Innovation of the first-line strategy optimized as abemaciclib with endocrine therapy based on the <i>ESR1</i>mutation of ctDNA for patients with HR-positive HER2-negative advanced metastatic breast cancer (JBCRG-M08; AMBER study).
Authors: Tetsuhiro Yoshinami, Shinsuke Sasada, Meiko Nishimura, Madoka Iwase, Chiya Oshiro, Kaori Terata, Mikiya Ishihara, Hiroko Bando, Masahiko Tanabe, Nobuyasu Yoshimoto, Sayuri Akiyoshi, Masahiro Takada, Hiroshi Ishiguro, Shigehira Saji, Satoshi Morita, Norikazu Masuda
Journal: Journal of Clinical Oncology (2024)

TPS1134 Background: Aromatase inhibitor (AI) + CDK4/6 inhibitor (CDK4/6i) has been established as a standard of care of 1 st line treatment for hormone receptor (HR)-positive/HER2-negative advanced metastatic breast cancer (AMBC). ESR1 mutations are considered to be one of the causes of acquiring resistance against the AI +CDK4/6i. PADA-1 trial showed that replacing AI with fulvestrant (FUL) as a partner of palbociclib (PAL) at occurrence of some ESR1 mutations improved progression-free survival (PFS) and PFS2, suggesting PAL should be used based on the strategy of selecting endocrine agents according to ESR1 mutation status by ctDNA analysis. On the other hand, we don’t know if this strategy is effective in the case of abemaciclib (ABM), another CDK4/6i established as the standard of care for AMBC. We are conducting a study to make evidence on this clinical question. Methods: This multicenter, single-arm phase II study is designed to evaluate the efficacy and safety of the strategy to replace AI with FUL for detectable ESR1 mutations in combination with ABM. Key eligibility criteria include patients receiving AI+ABM for at least 6 months as first-line treatment for HR-positive/ HER2-negative AMBC without progressive disease (PD). While continuing AI+ABM, ctDNA analysis will be performed at approximately 3, 9, 15 months from enrollment. If ESR1 mutation is identified at any point and non-PD is confirmed by CT, FUL+ABM will be initiated instead of AI+ABM. In patients with ESR1 mutations completely cleared by ctDNA analysis 6 months after the start of FUL+ABM, AI+ABM will be resumed (Re-AI+ABM arm); the Re-AI+ABM arm is intended to investigate whether the discontinuation of FUL will allow clones with ESR1 mutations to proliferate again. Primary endpoint is 2-year PFS rate in full analysis set. Key secondary endpoints include 2-year PFS rate by treatment sequences, and rate of disappearance of ESR1mutations in ctDNA with FUL+ABM. Plasma-SeqSensei Breast Cancer IVD Kit, which can simultaneously detect mutations in a wide range of six genes including ESR1, as well as PIK3CA, AKT1, ERBB2, KRAS, and TP53, is used for ctDNA analysis in this study. Based on PFS data in MONARCH3 study, the threshold and expected value of the 2-year PFS rate were estimated to be 45% and 55%, respectively, and target sample size was calculated as 160 patients. Patient enrollment started in December 2022 and run through December 2024; as of December 2023, 54 patients have been enrolled. Clinical trial information: 051220133.