tbuckley/cabot-search huggingface dataset:
An anti-EpCAM x anti-CD3 bispecific antibody, M701, for the treatment of malignant ascites due to epithelial cancer: Interim results of a prospective randomized controlled phase II trial.
Authors: Rongbo Lin, Jianming Xu, Rongrui Liu, Ning Li, Guiling Li, Tao Zhang, Jun Zhao, Jiayi Li, Meili Sun, Ke Wang, Hanxiang An, Weijie Zhang, Huiting Xu, Shan Zeng, Mingjun Zhang, Pengfei Zhou, Shaoyi Huang, Xiong Wang
Journal: Journal of Clinical Oncology (2024)

12060 Background: Malignant ascites (MA) is a significant complication in patients with late-stage epithelial cancer, associated with poor prognosis, reduced quality of life, and severe symptoms. It is usually caused by tumor cells seeding into the peritoneum, which obstructs lymphatic drainage and increases capillary permeability. Currently, there is no approved drug therapy specifically for the treatment of MA worldwide. Methods: Patients with MA due to epithelial cancer, who had received at least two prior systemic chemotherapy regimens, were enrolled and randomly assigned to the experimental arm (Arm E) and control arm (Arm C). Arm E received paracentesis and intraperitoneal (IP) infusions of 50, 400, 400, and 400μg of M701 on days 1, 4, 11, and 18. Additional M701 infusions could be given every 2 weeks without requiring punctures. Arm C received paracentesis alone as needed from day 1 to day 18. Both arms received systemic tumor treatment as determined by investigators. The primary endpoint was puncture-free survival (PuFS), defined as the time from random assignment to the next puncture or death, whichever occurred first. Secondary endpoints included overall survival (OS) and incidence of adverse events (AEs). Results: As of December 15, 2023, a total of 84 pts were enrolled, with 43 in Arm E and 41 in Arm C. The characteristics of Pts are outlined in the table. PuFS was significantly longer in Arm E compared to Arm C (median 54 vs 24 days, hazard ratios (HR) = 0.39, 95% CI 0.21-0.72, p=0.001). Subgroup analysis of PuFS indicated that patients with different types of cancer (gastric, colorectal and ovarian) all benefited from M701 infusion. OS analysis demonstrated a trend towards prolonged survival in Arm E compared to Arm C (median 113 vs 76 days, HR=0.56, 95% CI 0.31-1.03, p=0.0575). The 6-month survival rates were 35.2% and 15.8%, respectively. Subgroup analysis showed that patients with gastric cancer had significantly longer OS than the controls (median 128 vs 64 days, HR= 0.45, 95%CI 0.20-1.00, p=0.0438). Grade 3 or higher treatment-emergent AEs occurred in 52% of patients in Arm E and 57.5% of patients in Arm C. Serious AEs occurred in 38% and 50% of patients in the two arms, respectively. Only 2 cases of cytokine release syndrome (both grade 2) were reported in patients treated with M701. Conclusions: IP infusions of M701, based on systemic tumor therapy, were well tolerated and did not pose a higher risk compared to the control arm. Epithelial cancer patients with MA who received M701 treatment had longer PuFS and OS. These results are promising and support the pivotal trial of M701 as a novel treatment for MA. [Table: see text]
Chemotherapy-induced peripheral neuropathy research: A National Institute of Health (NIH) grant portfolio analysis.
Authors: Rachel D. Altshuler, Lori M. Minasian, Catherine Schweppe, Nina S. Kadan-Lottick
Journal: Journal of Clinical Oncology (2024)

12064 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating cancer treatment-related toxicity associated with considerable discomfort, functional loss, and impaired quality of life both acutely and long-term. Unfortunately, limited prevention and treatment options for CIPN currently exist. In this portfolio analysis, we sought to describe the landscape of CIPN research and identify gaps and opportunities to meet the needs of patients with CIPN. Methods: Using the NIH Query View Report system to search all NIH-funded competitive grants awarded between fiscal years 2014-2023, we identified 660 grants containing text pertaining to CIPN in the Abstract or Specific Aims. Grants were then manually reviewed and 480 were excluded as not specifically addressing CIPN. We categorized the final 180 grants as preclinical, clinical, or preclinical/clinical, followed by ascertainment of preclinical model, clinical population, CIPN assessment techniques, and/or clinical trial design, as applicable. Results: Of the 180 grants, 119 were preclinical, 51 clinical, and 10 with both preclinical and clinical components. The larger number of CIPN grants (n=27) were awarded in fiscal year 2022 vs. the lowest number (n=10) in 2014. Among the preclinical grants, 89% of grants utilized rodent models of CIPN, of which 19% proposed tumor-bearing models. A large majority of preclinical grants investigated paclitaxel (71%), followed by oxaliplatin (23%); none proposed studies of newer immune therapies. Among clinical grants, 41% (n=21) were interventional trials, 38% were prospective observational studies, and 15% retrospective studies. Clinical grants most frequently focused on breast cancer patients (41%), followed by unspecified cancer diagnoses (33%) and colorectal cancer (18%). For age of eligibility, 11% included patients younger than 18 years, while a higher proportion included 18-39 (82%), 40-64 (88%), and ≥65 (89%). The 21 interventional study grants investigated behavioral interventions (44%), pharmacological agents (28%), and devices (28%). Conclusions: The number of CIPN grants awarded annually by NIH have generally increased since fiscal year 2014, indicating increased investment by NIH. However, multiple gaps and opportunities remain. At the preclinical level, in addition to current rodent models and the narrow range of treatment exposures, novel strategies to mimic human CIPN conditions may improve translatability. Clinical studies are needed in younger patients that can be impacted by CIPN long-term. Also, there are important gaps in the CIPN-associated cancer diagnoses and therapy exposures (including novel agents) in current studies. Addressing the highlighted gaps may identify avenues to study additional interventions that achieve the highest impact in the populations that most need them.
Symptom burden in adolescents and young adults with cancer: A subgroup analysis of the enhanced, EHR-facilitated cancer symptom control (E2C2) trial.
Authors: Michael H. Storandt, Zhaohui Jin, Oudom Kour, Kathryn Jean Ruddy, Deirdre R. Pachman, Kurt Kroenke, Joan M. Griffin, Jessica Austin, Linda L. Chlan, Ewan Kemar Cobran, Jacob Greenmyer, Veronica Grzegorczyk, Wendy A Allen-Rhoades, Shawna L. Ehlers, Ashley Wilder Smith, Sandra A. Mitchell, Qian Shi, Andrea L. Cheville
Journal: Journal of Clinical Oncology (2024)

12065 Background: Incidence of cancer, including colorectal, breast, pancreas, kidney, and uterine cancer, is increasing in younger populations. Adolescents and young adults (AYA, defined as age 15-39) with cancer face unique challenges. This study aimed to characterize how symptom burden differs between AYA and non-AYA (aged 40+) patients with cancer. Methods: We performed a subgroup analysis of the E2C2 study, a cluster-randomized, pragmatic trial examining the effectiveness of routine symptom assessment and guideline-based management on patient-centered and healthcare utilization metrics during and following cancer treatment. Six symptoms [Sleep disturbance, Pain, Physical function impairment, Anxiety, Depression, and Energy deficit/fatigue (SPPADE)] were evaluated using 11-point numerical rating scales (NRS). Symptom severity was classified as mild (0-3), moderate (4-6), or severe (7-10). We conducted a subgroup analysis of symptom burden among AYA patients (defined as age 18-39 in this study), using their first-reported NRS scores. Results: The E2C2 cohort included 2,598 AYA patients and 38,061 non-AYA patients who completed &gt;1 SPPADE NRS on at least one survey. AYA patients were more likely than non-AYA patients to report severe anxiety ( p&lt;0.0001) and depression ( p&lt;0.0001) (Table). Non-AYA patients were more likely to report severe pain ( p=0.02179), fatigue ( p=0.0022), and physical function limitations ( p&lt;0.0001). Sociodemographic differences were also noted. A higher proportion of AYA patients held a bachelor’s degree or higher (38% vs 28%), were employed (73% vs 37%), and lived in an urban setting (67% vs 56%), compared to non-AYA patients. Non-AYA patients were more likely to have government insurance (63% vs 21%) and to be married (72% vs 59%). Conclusions: AYA patients with cancer were more likely to report severe depression and anxiety compared to their counterparts age 40 and above, underscoring the need for targeted and tailored psycho-oncology care for this population. [Table: see text]
Factors associated with sexual function and sexual satisfaction in young women with breast cancer.
Authors: Ana Ferrigno Guajardo, Alan Fonseca, Melina Miaja, Marlid Cruz-Ramos, Bryan Vaca-Cartagena, Fernanda Mesa-Chavez, Alejandra Platas, Ana Laura Rodriguez, Paula Anel Cabrera-Galeana, Alejandro Mohar, Cynthia Villarreal-Garza
Journal: Journal of Clinical Oncology (2024)

12062 Background: Young women with breast cancer (YWBC) are vulnerable to sexual dysfunction and dissatisfaction due to age-specific psychosocial concerns and treatment side effects. This study aimed to identify factors associated with sexual health in a prospective cohort of YWBC. Methods: Patients aged ≤40 yrs with non-metastatic BC from 3 referral centers completed emotional health, quality of life (QoL), and sexual health assessments at baseline, 6 mos, 1 yr, 2-3 yrs, and 4-5 yrs post-diagnosis. Sexual activity was defined as having had intercourse in the 4 wks preceding each assessment. Female sexual dysfunction (FSD) was defined as a total score &lt;26.55 in the Female Sexual Function Index (FSFI), while hypoactive sexual desire disorder (HSDD) was defined as a score &lt;5 in the desire subscale. Sexual enjoyment was classified with the Sexual Satisfaction Index (SSI), with &lt;110 indicating dissatisfaction. Results: A total of 474 patients with a median age of 36 yrs were included, of which most were married/in a domestic partnership (65%), unemployed (61%), and had an educational level &lt;high school (51%). Most had stage II (49%) or III (39%) disease. The most common molecular subtype was HR+/HER2- (53%), followed by HR-/HER- (26%) and HR+/HER2+ (14%). The prevalence of relevant outcomes at each assessment are shown in the Table. Factors associated with being sexually inactive were low educational level (χ 2 =7.7), being single (χ 2 =112.6), having children (χ 2 =8.12), and higher treatment side effects burden ( p=0.002). Factors associated with worse sexual function were being single (χ 2 =13.8), amenorrhea (χ 2 =40.8), HADS-D ≥8 (χ 2 =11.7), and HADS-A ≥8 (χ 2 =13.9). Factors associated with lower sexual satisfaction were low educational level (χ 2 =10.3), being single (χ 2 =15.5), having undergone bilateral oophorectomy (χ 2 =5.74), amenorrhea (χ 2 =8.48), HADS-D ≥8 (χ 2 =14.98,), and HADS-A ≥8 (χ 2 =13.91). Additionally, both FSFI and SSI scores directly correlated with QoL (QLQ SumScore) and body image (QLQ-BRBI), and inversely correlated with systemic therapy side effects (QLQ-BRST) ( p&lt;0.001). When analyzing sexual health outcomes according to type of treatment (total vs partial mastectomy, chemotherapy vs no, hormone therapy vs no, anti-HER2 agent vs no), no significant differences were found. Conclusions: Sexual dysfunction and dissatisfaction are highly prevalent in YWBC the first 5 yrs post-diagnosis. As poor sexual health correlates with inferior QoL, patients at an increased risk might benefit from early targeted interventions. [Table: see text]
Effect of anti CTLA-4 and PD-1 monoclonal antibodies on systemic SDF-1 and galectin-3 levels through NLRP3 and MyD-88 pathways in preclinical models.
Authors: Martina Iovine, Vincenzo Quagliariello, Margherita Passariello, Francesca Bruzzese, Giuseppe Palma, Antonio Luciano, Carlo Maurea, Massimiliano Berretta, Ilaria Giacobbe, Matteo Barbato, Vienna Giordano, Raffaele Arianna, Francesca Izzo, Paolo Antonio Ascierto, Irma Bisceglia, Maria Laura Canale, Claudia De Lorenzo, Nicola Maurea
Journal: Journal of Clinical Oncology (2024)

12032 Background: Immune checkpoint inhibitors (ICIs) have significantly changed the oncology clinic in recent years, improving survival expectations in cancer patients. ICI therapy have a broad spectrum of side effects from endocrinopathies to cardiovascular diseases. In this study, pro-inflammatory and pro-fibrotic effects of short-term ICIs therapy in preclinical models were analyzed. Methods: Firstly, in a human in vitro model, human cardiomyocytes co-cultured with hPBMC were exposed to ICIs (with CTLA-4 or PD-1 blocking agents, at 200 nM) for 72h. After treatment, production of DAMPs and 12 cytokines were analyzed in the supernatant through colorimetric and enzymatic assays. C57/Bl6 mice were treated with CTLA-4 or PD-1 blocking agents (15 mg/kg) for 10 days. Before (T0), after three days (T3) and ten days (T10), ejection fraction, radial/longitudinal strain were calculated by using echocardiography. Fibrosis, necrosis, hypertrophy and vascular NF-kB expression were analyzed through Immunohistochemistry. Myocardial expression of DAMPs (S100- Calgranulin, Fibronectin and Galectine-3), MyD88, NLRP3 and twelve cytokines have been analyzed. Systemic levels of SDF-1, IL-1β and IL-6 were analyzed before, during and after ICIs therapy. Results: Radial and longitudinal strain were decreased after 10 days of ICIs therapy. Histological analysis of NF-kB expression shows that short-term anti-CTLA-4 or anti-PD-1 treatment increased vascular and myocardial inflammation. Myocardial fibrosis and expression of galectin-3, pro-collagen 1-α and MMP-9 were increased after treatment with all ICIs. Both anti-CTLA-4 or anti-PD-1 treatments increased the expression of DAMPs, NLRP3 and MyD88 and induced both in vitro and in vivo the secretion of IL-1β, TNF-α and IL-6. Systemic levels of SDF-1, IL-1β and IL-6 were increased during and after treatment with ICIs. Conclusions: Short therapy with PD-1 and CTLA-4 blocking agents increases vascular expression of NF-kB, systemic SDF-1, IL-1β, IL-6 levels and myocardial NLRP3 in preclinical models. The overall picture of the study suggests new putative biomarkers of ICIs-mediated systemic and myocardial damages potentially useful in clinical cardioncology.
The influence of yoga and cognitive behavioral therapy on mediational relationships between insomnia and cancer-related fatigue: A URCC NCORP RCT in 550 cancer survivors.
Authors: Po-Ju Lin, Brian James Altman, Richard Francis Dunne, Lindsey Jean Mattick, Alisha Chakrabarti, Stephen Rajan Samuel, Umang Gada, Eva Culakova, Anthony John Jaslowski, Charles S. Kuzma, Karen Michelle Mustian
Journal: Journal of Clinical Oncology (2024)

12015 Background: Cancer-related fatigue (CRF) often co-occurs with insomnia and both are incapacitating adverse toxicities of cancer and its treatment which may persist months and years after the completion of treatment. Yoga and Cognitive Behavioral Therapy for Insomnia (CBT-I) are promising behavioral approaches for improving CRF and insomnia among cancer survivors. However, the influence of changes in insomnia resulting from participating in yoga or CBT-I on the subsequent changes in CRF is not fully understood. Methods: We conducted mediation analyses on data collected from a multicenter phase III RCT among cancer survivors who were randomized to receive 1) Yoga for Cancer Survivors (YOCAS, 75-min./session, 2x/wk. for 4 wks.), 2) CBT-I (90-min./session, 1x/wk. for 8 wks.), or 3) a behavioral placebo (ASCO recommended Survivorship Education, 75-min/session, 2x/wk. for 4 wks.). Brief Fatigue Inventory and Insomnia Severity Index were used to assess CRF and insomnia, respectively, at pre-, mid-, and post-intervention. Causal mediation analyses were conducted to estimate the influence of changes in insomnia at mid-intervention resulting from participating in YOCAS, CBT-I, or behavioral placebo on subsequent changes in CRF at post-intervention. Results: 550 survivors (93% female; mean age 57 years; 75% were breast cancer survivors) completed baseline and post-intervention assessments. YOCAS, compared to placebo, significantly improved CRF and insomnia at mid-intervention (CRF: -0.38±0.16, p = 0.01; Insomnia: -1.15±0.35, p &lt; 0.01) and post-intervention (CRF: -0.35±0.17, p = 0.03; Insomnia: -1.43±0.41, p &lt; 0.01). Among YOCAS participants, improvement in insomnia at mid-intervention significantly influenced the subsequent reduction in CRF (-0.14±0.06, p = 0.01) and accounted for 37% (95% CI: 0% - 78%) of the total reduction in CRF at post-intervention. CBT-I, compared to placebo, also significantly improved CRF and insomnia at mid- (CRF: -0.32±0.18, p = 0.06; Insomnia: -2.64±0.40, p &lt; 0.01) and post-intervention (CRF: -0.59±0.18, p &lt; 0.01; Insomnia: -4.95±0.46, p &lt; 0.01). Among CBT-I participants, the improvement in insomnia at mid-intervention significantly influenced the subsequent reduction in CRF (-0.40±0.09, p &lt; 0.01) and accounted for 60% (95% CI: 21% - 99%) of the total reduction in CRF at post-intervention. Conclusions: Both YOCAS and CBT-I effectively improve CRF and insomnia among survivors. 37%-60% of the reduction in CRF resulting from participating in YOCAS or CBT-I is due to improvement in insomnia. Clinicians should consider prescribing YOCAS yoga or CBT-I for survivors who experience CRF and insomnia. Clinical trial information: NCT02613364 .
Identifying optimized assessment of nerve damage during chemotherapy.
Authors: Tiffany Li, Hannah C Timmins, Fawaz Mayez Mahfouz, David Mizrahi, Lisa Horvath, Michelle L. Harrison, Peter S. Grimison, Michael Friedlander, Gavin M. Marx, Frances M. Boyle, David Wyld, Robert Henderson, Tracy King, Sally E. Baron-Hay, Matthew C Kiernan, Claudia Rutherford, David Goldstein, Susanna B Park
Journal: Journal of Clinical Oncology (2024)

12016 Background: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a significant and persisting toxicity of anticancer treatments, impacting dose delivery and quality of life. There is a lack of consensus on the optimal method of CIPN assessment in clinical settings. This study compared the validity and responsiveness of patient reported outcome measures (PROMs) against neurological, neurophysiological and sensory assessment approaches of CIPN. Methods: A multi-centre dual study design evaluated patients treated with neurotoxic chemotherapy across two cohorts: patients commencing treatment assessed prospectively and patients who completed treatment assessed cross-sectionally. CIPN was assessed via PROMs (EORTC-CIPN20, FACT/GOG-Ntx, PRO-CTCAE), neurological and neurophysiological assessment (Total Neuropathy Score, sural and tibial compound nerve amplitudes) and sensory functional measures (Grating orientation, Von Frey monofilament and 2-Point discrimination tasks). Convergent and known-groups validity were assessed cross-sectionally following treatment completion and responsiveness was evaluated prospectively during treatment. Neurological, neurophysiological, and sensory outcome measure scores were compared between high and low CIPN symptom reporters. Results: A total of 1,033 patients were recruited, incorporating 1,623 assessments. PROMs demonstrated superior ability to identify CIPN (convergent validity; α = 0.75-0.85, all P &lt; 0.001), to discriminate between CIPN severity (known-groups validity; all P &lt; 0.001) and to detect changes in CIPN development (responsiveness; Cohen’s d = 0.65-0.83) compared to neurological, neurophysiological and sensory assessment approaches. These other measures did not achieve threshold for convergent validity (α &lt; 0.7). and did not demonstrate acceptable responsiveness (Cohen’s d &lt; 0.5). Neurological, neurophysiological, and sensory outcome measures were significantly impaired in patients who were high CIPN symptom reporters compared to low (all P &lt; 0.05). Conclusions: PROMs represent a valid method of CIPN assessment, with preferential measurement properties over other approaches to assessing neuropathy. Adoption of PROMs in clinical practice will allow for accurate representation and early recognition of CIPN, leading to reduced long term morbidity in this key long-term toxicity in cancer survivors.
Using natural language processing to qualitatively assess goals of care conversations for patients with cancer.
Authors: Melissa Greene, Gloria Broadwater, Donna Niedzwiecki, Thomas William LeBlanc, Jessica Ma, David J. Casarett, Brittany Anne Davidson
Journal: Journal of Clinical Oncology (2024)

12035 Background: The importance of goals of care (GOC) discussions during end-of-life (EOL) care is well known. Institutions are increasingly tracking the frequency and timing of GOC documentation, but qualitative assessments of this content on a large scale have been limited given the person-power required and constraints of electronic health systems. Our aim is to use natural language processing to qualitatively assess the content of GOC documentation and associations with EOL care in patients who died with cancer. Methods: This is a retrospective review of patients with solid or hematologic malignancies who died between 2018-2022 with documented GOC notes in the last 12 months of life at a single academic National Cancer Institute-designated cancer center. Eight GOC components were identified based on prior literature: current understanding of patient’s illness, information preferences, disclosure of prognosis, goals, fears, acceptable function, trade-offs, and family involvement. GOC notes were extracted from the electronic health record and text annotation software Clinical Regex was utilized to search for the aggregate presence of these GOC components. Associations between these 8 components and receipt of aggressive EOL care (chemotherapy within 14 days of death, no hospice care, or hospice admission ≤3 days of death) were evaluated. Results: 2,031 patients met inclusion criteria. The most common disease sites were gynecologic (22.6%), gastrointestinal (20.3%), and thoracic (16.7%). The most common GOC components addressed were family involvement (75.0%), patient goals (72.0%), acceptable function, and decision making &amp; information preferences (both 65.8%). Only 5.4% had all 8 components addressed in documentation the last 12 months of life. More comprehensive GOC notes were associated with lower rates of aggressive EOL care; 73.2% received aggressive EOL when 0/8 components were documented, compared to 56.8% and 50.3% when 6 or 7 components were discussed, respectively. In multivariate logistic regression, GOC components documented (≤6 vs ≥7), primary tumor site, and inpatient palliative care referral were independent predictors of aggressive EOL care (p-values &lt;0.0001). Conclusions: GOC conversation documentation is largely not comprehensive. Increasingly comprehensive documentation is associated with a lower likelihood of receiving aggressive EOL care, suggesting opportunities to improve both the quality and documentation of GOC conversations may impact the EOL care for patients with cancer. Opportunities for increasing outpatient palliative care referrals may also improve the quality of the EOL experience for patients.[Table: see text]