tbuckley/cabot-search huggingface dataset:
Patterns and risk factors of immune-related adverse events in a real-world cohort with lung cancer receiving immunotherapy.
Authors: Xiao Hu, Anastasia Gurinovich, Stacey Pan, Yana Salei, Jeffrey Lin, Susan K. Parsons
Journal: Journal of Clinical Oncology (2024)

12130 Background: Immune checkpoint inhibitors (ICIs) have emerged as a core pillar of lung cancer (LC) therapy, but ICIs are commonly associated with a spectrum of immune-related adverse effects (irAEs). The real-world patterns and risk factors of irAEs in LC remain uncertain. Methods: Patients with LC newly started on ICIs between 10/01/2018 and 09/30/2021 were retrospectively collected from the Tufts Medical Center cancer registry and pharmacy records. irAEs occurring within 12 months after initiation of ICIs were identified. Univariable logistic regression was used to assess the risk factors of irAEs. Those with p-value&lt;0.20 were included in multivariable logistic regression analysis (MVA), along with clinically relevant factors. Results: Of 125 LC adult patients (median age: 70 years, 68 males), 104 had non-small cell lung cancer (NSCLC), 123 had advanced stages, and 16 had preexisting autoimmune diseases (ADs). Six patients were treated with dual-agent ICIs. Pembrolizumab was the most often used single agent (67.2%). In total 50 irAEs occurred in 39 patients. The most common irAEs were endocrinopathies (34%), pneumonitis (20%), dermatitis (14%), and gastrointestinal toxicity (14%) with the median onset time of 148, 136, 19, and 68 days, respectively. 70% of irAEs were grade 1 or 2. 44% of irAEs were treated with immunosuppression, 38% were referred to specialist care, and 30% required hospitalizations. 56% of irAEs resolved within 12 months and 67.9 % of those were rechallenged with ICIs. In exploratory univariable analyses among all the patients, age, small cell lung cancer (SCLC), PDL1 positivity (TPS≥1%), concurrent NSAIDs use, and radiation therapy had p&lt; 0.2. In MVA, SCLC remained significantly associated with irAEs (OR=4.14, 95% CI [1.50, 12.09], p=0.007). Among NSCLC subset (N=104), age, PDL1 positivity, concurrent NSAIDs, and acetaminophen use had p&lt;0.2. Age (OR=0.94, 95% CI [0.883, 0.990], p=0.026) and PDL1 positivity (OR=3.17, 95% CI [1.12, 9.87], p=0.036) remained significant in MVA (Table). Conclusions: Our study described the real-world patterns of irAEs in LC patients. SCLC was found to be an independent risk factor of irAEs in our cohort. In NSCLC, younger age and PDL1 positivity were associated with irAEs occurrence. Future studies are required to validate these findings in larger samples. [Table: see text]
The impact of cannabidiol (CBD) on aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS).
Authors: Nicole Margo Grogan Fleege, Elise Miller, Kelley M. Kidwell, Kelly L. Scheu, Kathleen A. Kemmer, Kevin Boehnke, Norah Lynn Henry
Journal: Journal of Clinical Oncology (2024)

e24060 Background: Although treatment with an AI for 5-10 years decreases 10-year breast cancer (BC) mortality by about 40%, up to 25% of patients will stop treatment early because of treatment-related, intolerable joint and muscle pain and stiffness, called AIMSS. Only acupuncture, duloxetine, and exercise have been shown to reduce AIMSS. While the exact underlying mechanism is unknown, it is thought to be due in part to ongoing systemic inflammation. CBD has anti-nociceptive and anti-inflammatory properties, making it a potential treatment option for AIMSS. Methods: Women with stage 0-3 hormone receptor-positive BC experiencing AIMSS (defined as worst joint pain ≥4/10 during prior 7 days that developed or worsened since starting AI therapy) were eligible for enrollment in this single arm, single center phase 2 open label clinical trial (NCT04754399). Patients received an FDA-approved formulation of CBD (Epidiolex), titrated over 4 weeks from 25 mg BID to 100 mg BID and then continued at maximum tolerated dose for a total of 15 weeks. Patient-reported outcomes (PRO) data were collected serially, including the Brief Pain Inventory (BPI) and the PROMIS Profile 29+2 v2.1. The primary endpoint was the number of CBD-treated patients with at least a 2-point reduction (minimal clinically important difference) in worst pain from baseline to 15 weeks. Statistical analysis was completed using paired t-tests and linear mixed models. Results: Of 39 eligible patients (Table 1), 11 discontinued participation early due to patient discretion (n = 6) or adverse event (n = 5). There were no grade 3-4 toxicities. Analyzing data from all 39 patients, there was an improvement in BPI worst pain (0-10 scale) of 0.13 per week of treatment after baseline (p &lt; 0.001), resulting in an average improvement in worst pain of 1.95 at the end of 15 weeks. Of the 28 patients who completed the study, 17 (60.7%) reported a ≥2-point improvement in BPI worst pain between baseline and week 15. There was a significant improvement in PROMIS T score at week 15 in both physical function (2.34, p = 0.01) and ability to participate in social roles and activities (2.71, p = 0.02). Conclusions: Treatment with CBD was associated with an improvement in joint pain for a subset of patients. Additional analyses are ongoing to further investigate the impact of CBD on AIMSS and to explore which patients are most likely to benefit from treatment with CBD. Clinical trial information: NCT04754399 . [Table: see text]
Network pharmacology-based strategy for screening active compounds and significant pathways of <i>huachansu</i> capsule on cancerous pain.
Authors: Luchang Cao, Xinmiao Wang, Jie Li
Journal: Journal of Clinical Oncology (2024)

e24054 Background: Cancerous pain (CP) is a troublesome symptom which can not be adequately controlled. It is reported by several clinical studies that Huachansu can help to relieve CP. However, its mechanism is unclear. In this study, we try to use network pharmacology to explore the underlying mechanism of Huachansu capsule (a capsule form of Huachansu) in the treatment of CP. Methods: Firstly, we collected Huachansu capsule’s active compounds from the literature. And then DrugBank and SwissTargetPrediction were used to obtain the drug targets. Genecards, OMIM, Drugbank, CTD, TTD and DisGeNET were used to gather CP-related genes. Cytoscape 3.7.2 was applied to construct the PPI network. The candidate genes were screened according to betweenness centrality (BC), closeness centrality (CC), degree centrality (DC) and local average connectivity (LAC). A PPI enrichment analysis was performed by MCODE. GO and KEGG analysis were carried out by Metascape. Results: In this study, we collected 11 active compounds and 235 CP-related targets of Huachansu capsule. Go analysis showed that the main related-biological functions included immune response, cytokine-mediated signaling, hypoxia. The main related-KEGG pathways included MAPK, AMPK, mTOR, erbB, Chemokine, TNF, HIF-1, toll-like receptor, PI3K-Akt, cAMP and NF-Kappa B signaling pathway. Conclusions: This study provides a systematic view of the polypharmacological characteristics of Huachansu capsule for pain treatment. Nevertheless, it still need to be verified by in vitro or in vivo studies.
Three-year disease-free survival after transanal vs. laparoscopic total mesorectal excision for rectal cancer (TaLaR): A randomized clinical trial.
Authors: Liang Kang, Ziwei Zeng, Huashan Liu
Journal: Journal of Clinical Oncology (2024)

3516 Background: Transanal total mesorectal excision (taTME) has gained significant traction as an effective approach for treating rectal cancer. Many previous studies reported positive relevant short-term results, histopathological results and associated complications of taTME compared to laparoscopic total mesorectal excision (laTME). Nonetheless, long-term oncological outcomes of taTME remain controversial. This study aimed to compare the 3-year DFS of taTME with laTME. Methods: We conducted a phase 3, randomized, open-label, noninferiority trial to compare the survival outcomes of taTME versus laTME in patients with rectal cancer located below the peritoneal reflection. This trial encompassed 16 hospitals across 10 provinces in China, with a total enrollment of 1,115 patients. We set the 3-year disease-free survival (DFS) and 5-year overall survival (OS) as the primary endpoints for analysis. The analysis of the 3-year DFS was conducted following a predefined modified intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT02966483. Results: The taTME group exhibited a 3-year DFS rate of 83.42%, and the laTME group achieved a 3-year DFS rate of 82.86%. The marginal difference of 0.56% between the DFS rates of the two groups (97.5% CI, −4.83 to 5.95, P &lt; 0.0001 for noninferiority) suggests comparable outcomes. Moreover, the rates of local recurrence were 3.90% in the taTME group and 3.62% in the laTME group, indicating similar degrees of localized tumor control. Regarding overall survival, the taTME group demonstrated a rate of 94.50% compared to 92.01% in the laTME group. In the taTME group, patients who are male or underwent neoadjuvant showed a higher 3-year OS than that in the laTME group. Conclusions: In patients with mid-low rectal cancer, the 3-year DFS of taTME is not inferior to that of laTME. This study provides evidence supporting the clinical effectiveness of taTME in the treatment of rectal cancer. Clinical trial information: NCT02966483 .
The relationship between PIK3CA mutations and survival in patients with human epidermal growth factor receptor 2–positive breast cancer receiving pyrotinib combined with trastuzumab for neoadjuvant treatment.
Authors: Qiyun Shi, Hao Tian, Dandan Ma, Juncheng Xuhong, Jia Ge, Feng Liu, Yang Lan, Peng Tang, Yan Liang, Li Chen, Linjun Fan, Yi Zhang, Tao Luo, Xiuwu Bian, Jun Jiang, Xiaowei Qi
Journal: Journal of Clinical Oncology (2024)

e12637 Background: Our previous study suggested that HER2-positive breast cancer patients with activated mutations in PIK3CA are less likely to achieve a pathological complete response (pCR) from pyrotinib combined with trastuzumab in the neoadjuvant setting. The relationship of PIK3CA mutations and survival remains unknown. Methods: The genomic characteristics of 425 cancer-related genes from the archived tumour blocks of 50 patients enrolled in a prospective neoadjuvant pyrotinib and trastuzumab plus chemotherapy clinical trial (ChiCTR1900022293) were assessed by next-generation sequencing (NGS). The relationship between PIK3CA mutations and event-free survival (EFS) and overall survival (OS) were explored. Results: Among the cohort of 50 cases, five patients dropped out during treatment due to various reasons, whereas the other 45 patients were followed up until August 31, 2023. The median follow-up was 36.1 months, and mEFS and mOS were not reached yet. Kaplan-Meier estimated 3-year EFS rate and OS rate were 91.1% (95% confidence interval [CI]=83.2%-99.8%) and 97.1% (95% CI=91.8%-100%), respectively. Patients with wild-type PIK3CA tended to achieve a better 3-year EFS rate (96.2% vs 63.2%, hazard ratio [HR]=0.18, 95% CI=0.02-1.59, log-rank P = 0.081) compared with the patients with mutated PIK3CA. Besides, patients with pCR showed a better 3-year EFS rate (96.2% vs 84.2%, HR=0.16,95% CI=0.02-1.45, log-rank P = 0.063) compared with the patients without pCR. Conclusions: HER2-positive breast cancer patients with activated mutations in PIK3CA are less likely to benefit from pyrotinib combined with trastuzumab in the neoadjuvant setting, but this conclusion still needs to be confirmed by large-sample studies and long-term follow-up results. Clinical trial information: 1900022293.
The association between age, toxicity and outcomes of abemaciclib treatment in HR+/HER2- metastatic breast cancer.
Authors: Tanja Ovcaricek, Erika Matos, Simona Borstnar, Domen Ribnikar, Cvetka Grasic Kuhar, Kaja Cankar
Journal: Journal of Clinical Oncology (2024)

e13062 Background: The efficacy and safety of abemaciclib in patients (pts) with HR+/HER2− metastatic breast cancer (MBC) was demonstrated in the MONARCH clinical trials; however, real-world evidence is lacking, particularly in elderly pts. The dose reduction strategy used in the MONARCH trials has been shown to be an effective way of managing toxicity without compromising survival. Here, we provide real-world data on the efficacy and safety of abemaciclib treatment, focusing also on elderly pts with HR+/HER2− MBC and the association between abemaciclib dose reduction and survival. Methods: The efficacy and safety of abemaciclib in patients (pts) with HR+/HER2− metastatic breast cancer (MBC) was demonstrated in the MONARCH clinical trials; however, real-world evidence is lacking, particularly in elderly pts. The dose reduction strategy used in the MONARCH trials has been shown to be an effective way of managing toxicity without compromising survival. Here, we provide real-world data on the efficacy and safety of abemaciclib treatment, focusing also on elderly pts with HR+/HER2− MBC and the association between abemaciclib dose reduction and survival. Results: The median age of 134 pts was 62 yrs (IQR, 54-71), with 40 pts (29.9%) older than 70 yrs. Median rwPFS (mrwPFS) with abemaciclib + endocrine therapy in the ≥70 vs &lt;70 age group was 15 vs 17 months (HR:1.1, 95% CI 0.70-1.76; p=0.65) and median OS (mOS) was 25 vs 34 months (HR:1.4, 95% CI 0.82-2.39, p=0.21). The most common rwAEs are shown (Table). Abemaciclib dose reductions occurred in 40% of pts ≥70 yrs of age compared to 28% of younger pts (χ2 (1)=1.98; p=0.22). There was no difference in mrwPFS between pts who had a dose reduction and those who did not (mrwPFS 15 vs 17 months (HR: 1.03, 95% CI 0.65-1.63, p=0.91) and mOS 28 vs 30 months (HR: 1.16, 95% CI 0.68-1.99; p=0.58)). Conclusions: The results of our study support the efficacy and safety of abemaciclib treatment in pts with HR+/HER2- MBC in real-world clinical practice. Age did not appear to be an important factor associated with higher rates of toxicity and similar efficacy of abemaciclib was demonstrated in the elderly pts population compared to younger pts. Importantly, abemaciclib dose reductions did not compromise survival. Clinical trial information: ERIDNPVO-0060/2022. [Table: see text]
Adenocarcinoma in multiple adenomatous polyps: An analysis of demographic and socioeconomic factors.
Authors: Amit Johanis, Kat Chin, Amaan Zafar, Rick Robin, Peter T. Silberstein, Craig Heise, Beau Hsia
Journal: Journal of Clinical Oncology (2024)

e15619 Background: Adenocarcinoma in multiple adenomatous polyps (AMAP) is a form of gastrointestinal cancer characterized by adenomatous polyps in the gastrointestinal mucosa and distinct lesions found outside the intestines. A rare form of cancer, AMAP can be traced back to mutations in the APC gene, with higher rates of mutation correlating with worse prognosis. There is an association with familial adenomatous polyposis, which can lead to colorectal cancer in patients as young as 15. Examining demographic statistics on AMAP from the National Cancer Database (NCDB) sheds light on this rare form of colorectal cancer, unlocking new possibilities for diagnostics and treatment. Methods: A retrospective cohort analysis identified 193 patients with AMAP from the 2004-2020 NCDB using ICD-O-3 Code 8221 to identify them. Demographic factors such as age, sex, treatment type, and Charles/Deyo score were explored with descriptive statistics. Linear regression analysis was utilized to study incidence trends. Results: A total of 193 cases of histologically confirmed AMAP were retrieved from the 2004-2020 NCDB with a slight decline in incidence rates during this time (R² = 0.39). The majority of patients were male (55%), White (86%), privately insured (46%), and resided in metropolitan areas with a population size of at least one million (60%). Most patients also comprised the top two income quartiles based on median household income (64%). The mean age at diagnosis was 56.5 years (SD = 19.15, range = 15 - 90). The top primary sites affected were the Colon (26%), Sigmoid Colon (16%), and Rectum (11%). Furthermore, most patients were treated surgically (88%) with the average tumor size of 35.3 mm (SD = 20.5, range = 5.0 - 77.0). More patients received chemotherapy (28%) than radiation therapy (10.4%), with few patients receiving hormone therapy (0.5%) and none receiving immunotherapy. Over half (51%) of the patients were categorized as experiencing Stage 0 and Stage 1 cancer according to the NCDB Analytic Stage Group. The vast majority of patients (74%) had no comorbidities (Charlson-Deyo = 0) and did not receive any palliative care (97%). Conclusions: Our NCDB analysis on AMAP is a novel examination that provides insight into various demographics to better understand the disease. The majority of patients were males with adenocarcinoma lesions most commonly diagnosed in the colon and rectal areas, consistent with previous studies on multiple adenomatous polyps. Our analysis revealed that the majority of patients diagnosed with AMAP tend to be White, privately insured, reside in metropolitan areas, and hail from the top two quartiles of median household income. Additional research is required to gain a greater understanding of the demographic and socioeconomic factors that are important for accurate diagnosis, effective treatments, and improved outcomes.
Antibody-drug conjugates (ADC) in patients with advanced/metastatic HER2-low expressing breast cancer: A systematic review and meta-analysis.
Authors: Isabella Michelon, Maria Inez Dacoregio, Maysa Vilbert, Jonathan N. Priantti, Caio Castro, Lucas Vian, Ludimila Cavalcante
Journal: Journal of Clinical Oncology (2024)

e13174 Background: Historically, HER2-targeted therapies failed to improve survival of patients with HER2-low-expressing tumors. Recently, trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate (ADC), demonstrated superior outcomes compared with treatment of physician´s choice (TPC) in this population. Other ADCs have also shown encouraging results, including sacituzumab govitecan (SG), MRG002, and RC48-ADC. Hence, we performed a systematic review and meta-analysis to assess the effectiveness of ADCs in patients with HER2-low advanced/metastatic (a/m) breast cancer (BC). Methods: We searched PubMed, Embase, and Cochrane databases and ASCO, ESMO, and SABCS websites for studies evaluating ADCs on patients with HER2-low a/mBC. Outcomes of interest were objective response rate (ORR); disease control rate (DCR); clinical benefit rate (CBR); progression-free survival (PFS); and overall survival (OS). We used R software (v.4.2.2) and random effects models for all analyses. Heterogeneity was assessed using I 2 test. Results: Overall, 12 studies were included (3 real-world studies and 9 clinical trials), with 1,292 HER2-low a/mBC patients, 378 received TPC, and 914 received ADCs. Most were treated with T-DXd (63%, n=572), SG (29%, n=268), MRG002 (6%, n=56), and RC48-ADC (2%, n=18). Median age ranged from 48.1 to 58 years, and follow-up from 9.5 to 18.4 months. Patients treated with T-DXd achieved a significantly higher ORR and DCR compared to those who received SG, RC48-ADC, and MRG002 (Table). CBR was numerically higher in patients on T-DXd than those on SG but did not reach a significant difference. Patients with HR-positive tumors treated with SG had an ORR of 45% (95% CI 23 – 67%), and patients with pure HER2-low treated with any ADC, had an ORR of 38% (95% CI 30 – 45%). In the pooled analysis of 3 RCTs, ADCs significantly prolonged PFS compared with TPC (n=963, HR: 0.44, 95% CI 0.32 – 0.61, I 2 = 66%, p&lt;0.001), and OS (n= 680, HR: 0.56, 95% CI 0.36 – 0.89, I 2 = 73%, p=0.015). Patients on ADCs also achieved a greater anti-tumor response than TPC, including better ORR (OR: 4.18, 95% CI 2.40 - 7.28, I 2 = 52%, p&lt;0.001), DCR (OR: 2.82, 95% CI 2.06 - 3.85, I 2 = 7%, p&lt;0.001), and CBR (OR: 3.41, 95% CI 2.36 - 4.93, I 2 = 25%, p&lt;0.001). Conclusions: Our systematic review and meta-analysis supports the efficacy of ADCs in HER2-low a/mBC patients over TPC. Future studies should focus on bringing ADCs into earlier lines of therapy in this population.Anti-tumor activity of ADCs presented as overall % (95% CI). [Table: see text]
Human-AI teams to improve accuracy and timeliness of oncology trial prescreening: Preplanned interim analysis of a randomized trial.
Authors: Ravi Bharat Parikh, Matthew Guido, Anthony Girard, Yang Li, Likhitha Kolla, Jinbo Chen, Ezekiel J. Emanuel
Journal: Journal of Clinical Oncology (2024)

1524 Background: Identifying eligible patients for oncology clinical trials (“prescreening”) relies on manual chart review by clinical research coordinators (CRCs), which is time-consuming and often inaccurate. Consequently, 70% of patients with cancer who meet trial eligibility criteria are not offered participation. Natural language processing (NLP) may improve the accuracy and timeliness of prescreening. Methods: This was a preplanned interim analysis of a paired-design noninferiority trial, powered to assess timeliness. We adapted NLP algorithms to identify 13 common eligibility criteria related to cancer type/stage, prior systemic therapy, actionable biomarkers, and response criteria. NLP systems performed optical character recognition, entity and relationship extraction, and natural language inference through deep learning and symbolic AI techniques. Deidentified unstructured electronic health records (EHRs) from real-world patients with non-small cell lung (NSCLC) or colorectal (CrCa) cancer were presented to CRCs via a secure platform. Two CRCs were randomized 1:1 to view blocks of 20 charts each with (Human+AI) or without (Human-alone) NLP annotations. In pre-trial assessment, the CRCs had 86% inter-rater agreement. The primary outcome was overall chart-level accuracy, defined as percent of the 13 CRC-coded eligibility items matching a gold standard set, determined by 2-3 clinicians blinded to experimental arms. Paired t-tests compared overall accuracy (noninferiority margin 5%) and criteria-specific accuracy. Significant differences were assessed for superiority using two-sided paired t-tests. Mann-Whitney tests compared the secondary outcome of timeliness (time per chart review). Results: Among 74 (40 NSCLC; 34 CrCa) of a planned 400 patients, overall accuracy for Human+AI was noninferior to Human-alone (78.7% vs. 76.7%, mean difference 2.0%, p&lt;0.001 rejecting inferiority); both were greater than AI-alone (63.5%). Superiority for Human+AI was demonstrated for RECIST response, but not for overall nor other criteria-specific accuracy (Table). Median time per review was lower for Human+AI than Human-alone (34.1 vs 43.9 min, adjusted p=0.05). Conclusions: Human+AI teams can improve timeliness of trial prescreening with noninferior accuracy. This platform is being used for eligibility assessment in an ongoing clinical trial. [Table: see text]