tbuckley/cabot-search huggingface dataset:
Unveiling the impact: Exploring malnutrition rates in patients with cancer and its association with anticancer treatments.
Authors: Roshini Pradeep, Kunal Deora, Emily Danca, Tarra Young, Kelly Mott, Ashley Chezik, Neychelle Rocca, Andrzej Piotr Kudelka
Journal: Journal of Clinical Oncology (2024)

189 Background: Malnutrition is a common cause of morbidity and mortality in patients with cancer. Malnutrition is seen in 40 to 80% of patients with cancer. Recent literature has shown loss of lean body mass in cancer population can be an independent factor for poorer outcomes. Anorexia, the loss of appetite has been either secondary to the disease itself or as a side effect of treatment. The mechanism of anorexia development is due to physiologic alteration in metabolism during carcinogenesis. Hence, it becomes important to screen for malnutrition in all patients with diagnosis of cancer. Methods: This single-center cohort study, conducted between January 15, 2024, and February 9, 2024, involved 106 patients receiving outpatient oncology care. Patients aged 18 to 90 years who consented to participate were administered the Mini Nutritional Assessment (MNA) questionnaire at the oncology registration desk. Exclusion criteria included patients with a dietician and those with pure nonmalignant hematological diagnoses. Data analysis comprised identifying patients at risk of malnutrition (8-11 points) or malnourished (0-7 points) using the MNA scale, followed by retrospective chart review. Primary outcomes focused on identifying prevalent cancer types among malnourished or at-risk patients, while secondary outcomes included comparing malnutrition proportions among different treatment groups and assessing gastrointestinal tract metastases and common causes of malnutrition. Results: The data encompassed 106 patients, among whom 29 (27.3%) were identified as at risk of malnutrition, while 9 (8.4%) were malnourished. Notably, a majority of at-risk or malnourished patients (60.5%) were classified as overweight or obese. The most prevalent cancers among these patients were breast cancer (26.3%), genitourinary cancer (23.6%), and gastrointestinal cancer (18.4%). Chemotherapy use was noted in 16 (42.1%) patients, immune checkpoint inhibitor treatment in 12 (31.5%), and a combination of both in 7 (18.4%). Gastrointestinal metastasis was observed in 5 (13.1%) patients. Among those at risk of malnutrition, the primary contributing factors identified were tumor impact and location (63.1%), diarrhea (18.4%), and fatigue (18.4%). Conclusions: The study underscores the significant prevalence of malnutrition risk among cancer patients, emphasizing the importance of systematic screening during outpatient oncology follow-ups.
The use of adjuvant radiotherapy in resected adult intracranial atypical meningioma in United States: A SEER analysis.
Authors: Jayson L. Co
Journal: Journal of Clinical Oncology (2024)

27 Background: It is unclear whether adjuvant external beam radiotherapy (EBRT) in atypical meningiomas after surgical resection provided overall survival advantage. Although meta-analysis were previously reported, there is heterogeneity in the included studies. With lack of prospective trial, we rely on observational data for management. This project aims to determine if the addition of adjuvant EBRT after resection compared to resection alone in atypical meningioma is associated with better prolonged survival among patients within United States. Methods: The National Cancer Institute Surveillance, Epidemiology and End Results database was queried for list of patients diagnosed with atypical meningioma from 2000 to 2020 according to International Classification of Disease (ICD) for Oncology, third edition with morphology codes 9539/0 and 9539/1.This was limited to intracranial location. Rate of dying among those receiving adjuvant EBRT after surgery for atypical meningiomas was compared to the rate of dying of those who had resection alone without adjuvant EBRT postoperatively. Other covariates included, age at diagnosis, gender, marital status, race, tumor laterality, tumor site, tumor, extent of resection and household median income. Chi-squared test was used to test the association between institution of adjuvant EBRT and other co-variates for categorical variable. Cox-proportional analysis was used to test the association between adjuvant EBRT and death. Observed survival was estimated using Kaplan-Meyer method. Survival curves were generated for both cohorts and log rank test was performed. Results: A total of 3,328 patients were included in analysis.1,004(30.17%) patients received adjuvant EBRT and 767(23.05%) died in the entire cohort. Rate of dying in the entire cohort is 43.84 per 1,000 person-years. Death rate for patients receiving adjuvant EBRT is 44.95 per 1,000 person-years, while patients who did not receive adjuvant EBRT had a death rate of 40.95 per 1,000 person-years. Patients aged 80 years or older, divorced and separated tend not to receive adjuvant EBRT, while patients with tumor size of 51-100mm and 101-200mm are more likely to receive adjuvant RT. Crude rate ratio among those patients receiving RT compared to the rate of those who did not receive adjuvant RT is 0.91 (95% CI: 0.76-1.07). Adjusting for possible confounders did not change the rate ratio between adjuvant EBRT compared to resection alone. Extent of resection did not modify the effect of adjuvant RT to death (likelihood ratio test-0.363). Survival analysis using Kaplan Meier curve showed no difference whether a patient received adjuvant EBRT or not (log rank test-0.238). Conclusions: There is no clear evidence on the survival benefit for use of adjuvant EBRT in resected atypical meningioma compared resection alone. This is true both in incomplete and completely resected atypical meningiomas.
Exploratory study of PD-1 inhibitors for recurrent meningioma.
Authors: Yali Wang, Feng Chen, Zhen Wu, Wenbin Li
Journal: Journal of Clinical Oncology (2024)

26 Background: Meningiomas are the most common primary intracranial tumor. Some patients still have poorly controlled conditions after multiple surgeries and radiotherapies. More effective treatment methods are urgently needed. Previous studies have suggested that meningioma may shape an inhibitory tumor immune microenvironment and achieve immune escape by expressing programmed cell death ligand 1 (PD-L1) and other factors. Immune checkpoint inhibitors (ICIs) such as PD-1 inhibitors have shown promising efficacy in cases, but large-sample studies are needed to confirm these findings. Methods: Recurrent meningioma patients were included and treated with PD-1 inhibitors until tumor progression or intolerance occurred. The efficacy evaluation of enrolled patients used the Response Assessment in Neuro-Oncology (RANO) criteria. The primary endpoint was progression-free survival at 6 months (PFS-6), and secondary endpoints were progression-free survival at 12 months (PFS-12) and overall survival (OS). Adverse events were also recorded. Regular imaging follow-ups were conducted, and clinical characteristics were collected for survival analysis. Peripheral blood lymphocyte subsets and cytokines were detected before and after treatment, and tumor paraffin sections were used for immunohistochemical detection of relevant molecular markers. Results: A total of 35 recurrent meningioma patients (10 grade I, 14 grade II, 11 grade III) were included. Among all grades of patients, the median PFS was 9 months, PFS-6 was 63.6%, and PFS-12 was 47.6%. In grade I patients, the median PFS was 14 months, PFS-6 was 83%, and PFS-12 was 67%. In grade II/III patients, the median PFS was 9 months, PFS-6 was 58.9%, and PFS-12 was 42%. Among all grades of meningioma patients, PFS was significantly correlated with Ki-67 index (P = 0.021) and tumor progression times (P = 0.019). In grade II/III meningioma patients, PFS was only correlated with tumor progression times (P = 0.012). Twenty-five patients had stable disease, and seven patients had disease progression, with no patient achieving partial or complete remission. There was no significant correlation between tumor mutation burden (TMB) and PFS. Further immunohistochemical analysis of tumor tissues in three recurrent high-grade patients revealed varying degrees of increase in local CD3+, CD4+, CD8+ and PD-1+ T lymphocytes after treatment compared to baseline. Conclusions: Our study suggests that PD-1 inhibitors may prolong PFS in recurrent meningioma patients (especially high-grade) with good drug safety, warranting further exploration. Recurrent meningiomas have an immunosuppressive tumor microenvironment, and PD-1 inhibitors may improve the immune status of tumor microenvironments. Clinical trial information: NCT04728568 .
Effect of oncolytic Newcastle disease virus harboring PTEN gene on pancreatic adenocarcinoma growth through inhibition of PI3K/mTOR signaling and promotion of apoptosis.
Authors: Hyun Jang
Journal: Journal of Clinical Oncology (2024)

49 Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and intractable cancer, warranting the need for more effective therapies. Cell proliferation, progression, and severity in PDAC are highly activated owing to KRAS mutations and low PTEN expression. Methods: A recombinant Newcastle disease virus (rNDV) harboring PTEN (rNDV-PTEN) was constructed to infect PDAC cells to artificially induce PTEN expression. The cancer killing effect of the rNDV-PTEN virus was observed in an in vitro assay, and 10 7.0 pfu/dose(0.1 ml) of the rNDV-PTEN virus was inoculated through intravenous injection into a PANC-1 cell transplanted mouse to prove the tumor growth inhibition effect. Apoptotic signaling-related proteins were analyzed with Western blotting and qPCR assays based on the mRNA. During the treatment, biomarkers were also analyzed. Results: Factitious PTEN expression in KRAS-mutated PDAC cells following rNDV-PTEN infection lowered PI3K/AKT/mTOR signaling, induced PDAC cell death, and suppressed tumor growth. PTEN overexpression promoted apoptotic and autophagic signaling pathways in PANC-1 cells and orthotopic xenograft mice. rNDV-PTEN has substantial cancer cell-killing effects and inhibits tumor growth. rNDV-PTEN injection into animals did not elicit an immune response against rNDV and improved blood parameters, such as glucose, triglyceride, and total cholesterol levels. Conclusions: rNDV-PTEN showed a strong tumor-suppressive effect on PDAC, which was caused by an abnormally activated PI3K/AKT/mTOR signaling pathway due to KRAS mutations and PTEN loss. We also showed that rNDV-PTEN is relatively safe for use in cancer therapy. Further studies using patient-derived PDAC cells with the same genetic background, as well as more extensive animal safety tests, are required to demonstrate rNDV-PTEN as a PDAC therapeutic. However, PTEN gene-containing rNDV may be a very promising therapeutic candidate for pancreatic cancer treatment.
Single centre real world data on disease profile and outcome of 700 patients with penile cancer treated with curative intent at an Indian cancer centre.
Authors: Gagan Prakash, Amandeep Arora, Mahendra Pal, Santosh Menon, Vedang Murthy, Ankit Misra, Priyamvada Maitre, Ajit Gujela, Manoj Tummala, Uday Chandankhede, Anand Mohan, Shraddha Bonkar Dethe, Aparna Ringe-Katdare, Archi Agrawal, Amit Joshi, Kumar Prabhash, Vanita Noronha, Ganesh Bakshi
Journal: Journal of Clinical Oncology (2024)

121 Background: Globocan 2022 reported that there are close to 10000 newly diagnosed penile cancer (PeCa) patients annually in India, which contributes to around 27% of the world’s burden of this disease. With the rarity of this male genitourinary cancer globally and absence of level I evidence on most aspects of the disease, real world data from a single Centre assumes importance and this retrospective study highlights the clinico-demographic profile, oncological outcome and surgical complications in patients treated with a curative intent. Methods: We retrospectively reviewed our prospectively maintained institutional database for patients with PeCa treated with curative intent from 2013 to 2021. Data was collected for demographic variables, clinico-pathological characteristics, post-operative complications and oncological outcomes. Descriptive data were expressed as mean / median / proportions. The Kaplan Meier method was used to calculate the cancer specific survival (CSS) of the patients, stratified by pN status. Results: From 2013 to 2021, 700 patients were treated for PeCa at our centre with curative intent, with a median age of 54 years (IQR 44-62) and a mean BMI of 24.1 kg/m 2 . Around 40% of the patients had history of tobacco use. The clinico-pathological features and Clavian Dindo complication rates are summarized in the table. With a median follow-up of 42 months, the CSS for cN0 patients under observation for their groins was 97.3%.CSS for patients with pN0, pN1, pN2 and pN3 was 90.6%, 79.4%, 71.4% and 55%. Amongst pN3, 24.3% received adjuvant chemo alone, 23.7% received adjuvant RT/CTRT alone while 33.7% received both adjuvant chemo and RT.CSS of pelvic nodal pN3 patients was 35% compared to 71% of inguinal perinodal extension pN3. Conclusions: Our series, one of the largest reported from a single centre, highlights the real world oncological outcome of PeCa patients. We reemphasize the importance of addressing inguinal nodes early and adequately and the worser outcome of pN3 due to pelvic node involvement compared to pN3 due to extra nodal extension of inguinal nodes. [Table: see text]
Infusion-related reactions from immune checkpoint inhibitors: A proportional and network meta-analysis.
Authors: Yu Fujiwara, Kazuya Tsuchiya, Mako Koseki, Jonathan Estaris, Evelyn Elias, Fnu Chesta, Kensuke Takaoka, Yoshito Nishimura, Dharmesh Gopalakrishnan, Igor Puzanov
Journal: Journal of Clinical Oncology (2024)

38 Background: Immune checkpoint inhibitors (ICIs) have become the standard of care for the treatment of patients with solid tumors. Infusion-related reactions (IRRs) to ICIs have been reported in up to 20%, but the incidence varies among ICIs. Therefore, we aimed to report and compare the incidence of IRRs to each ICI therapy. Methods: We searched PubMed/MEDLINE, Embase, and Web of Science to identify phase 3 randomized controlled trials (RCTs) evaluating ICIs (CTLA-4, PD-1, PD-L1, and LAG-3 inhibitors) in solid tumors. We performed a random-effects model network meta-analysis to compare the odds ratio (OR) of IRRs by using RCTs comparing dual ICIs, ICI monotherapy, and placebo/observation. For a proportional meta-analysis, treatment arms evaluating ICI monotherapy, or dual ICIs, were selected to pool the incidence of IRRs. Results: A total of 25,250 patients from 47 phase 3 RCTs were included in the analysis. A network meta-analysis of treatment-related IRRs included 10 RCTs and showed that avelumab (OR 70.2, 95% confidence interval [CI]: 4.32-1140) and atezolizumab (40.72, 2.47-671.4) had a significantly higher risk of treatment-related IRRs compared with placebo/observation. Network ranking revealed that avelumab, atezolizumab, and relatlimab plus nivolumab were the top three therapies with risk of treatment-related IRRs. Proportional meta-analyses revealed that the pooled incidence of treatment-related IRRs was 5.39% for PD-1 plus CTLA-4 inhibitors, 8.25% for PD-L1 (avelumab: 13.1%, non-avelumab: 1.93%), 1.97% for CTLA-4, and 1.95% for PD-1 inhibitors. Results of immune-related IRRs were relatively consistent with those of treatment-related IRRs (Table). Conclusions: Avelumab has the highest risk of IRRs followed by atezolizumab and dual ICIs. This comparative study provides insight into the incidence of IRRs with ICI regimens. These results are useful in assessing which systemic therapies are responsible for IRRs, particularly when ICIs are combined with other agents. [Table: see text]
PD-1 blockade with camrelizumab after chemoradiotherapy in nasopharyngeal carcinoma.
Authors: Jun Ma, Ying Sun, Ye-Lin Liang, Xu Liu, Liangfang Shen, Guangyuan Hu, Guorong Zou, Ning Zhang, Chuanben Chen, Xiaozhong Chen, Xiao-Dong Zhu, Yawei Yuan, Kunyu Yang, Feng Jin, Shu-Bin Hong, Hongyun Zhao, Ji-Bin Li
Journal: Journal of Clinical Oncology (2024)

129 Background: Approximately 30% of locoregionally advanced nasopharyngeal carcinoma (NPC) experience disease relapse despite definitive chemoradiotherapy. The programmed death-1 (PD-1) blockade camrelizumab has demonstrated considerable value in recurrent/metastatic NPC, while its role in locoregionally advanced NPC is worth exploring. Methods: We conducted a randomized, open-label, phase 3 trial to evaluate adjuvant camrelizumab in locoregionally advanced NPC after definitive chemoradiotherapy. Patients with T4N1M0 or T1-4N2-3M0 NPC who have undergone induction chemotherapy and concurrent chemoradiotherapy were randomized in a 1:1 ratio to receive adjuvant camrelizumab (200mg intravenously once every 3 weeks for up to 12 cycles; Camrelizumab group) or observation ( Standard-therapy group). The primary endpoint was event-free survival (freedom from randomization to locoregional recurrence, distant metastasis, or death from any cause). The secondary endpoint included locoregional recurrence-free survival, distant metastasis-free survival, overall survival, safety, and quality of life. Results: A total of 226 patients were randomized to the Camrelizumab group and 224 to Standard-therapy group. At a median follow-up of 37 months, the 3-year event-free survival was 86.9% in the Camrelizumab group and 77.4% in the Standard-therapy groups (stratified hazard ratio, 0.61; 95% confidence interval [CI], 0.38 to 0.96; P = 0.03). Grade 3 or 4 adverse events were reported in 11.2% patients in the Camrelizumab group and 3.2% of those in the Standard-therapy group. The most common adverse event of grade 3 or 4 was leukopenia (4.9% and 1.4%, respectively). There was no meaningful deterioration in quality of life associated with the use of adjuvant camrelizumab. Conclusions: Adjuvant PD-1 blockade with camrelizumab significantly improved event-free survival, with mild toxicity, highlighting its compelling role in the management of locoregionally advanced NPC. (DIPPER,ClinicalTrials.gov numberNCT03427827). Clinical trial information: NCT03427827 . [Table: see text]
Proportional Hazards Violations in Phase 3 Cancer Clinical Trials: A Potential Source of Trial Misinterpretation
Authors: Timothy A. Lin, Zachary R. McCaw, Alex Koong, Christine Lin, Joseph Abi Jaoude, Roshal Patel, Ramez Kouzy, Molly B. El Alam, Alexander D. Sherry, Sonal S. Noticewala, Clifton D. Fuller, Charles R. Thomas, Ryan Sun, J. Jack Lee, Ruitao Lin, Ying Yuan, Yu Shyr, Tomer Meirson, Ethan B. Ludmir
Journal: Clinical Cancer Research (2024)

Survival analyses of novel agents with long-term responders often exhibit differential hazard rates over time. Such proportional hazards violations (PHV) may reduce the power of the log-rank test and lead to misinterpretation of trial results. We aimed to characterize the incidence and study attributes associated with PHVs in phase III oncology trials and assess the utility of restricted mean survival time and maximum combination test as additional analyses.
Effect of deconvoluting single-cell transcriptomics on cellular programs regulated by cell-cell communication in colorectal cancer.
Authors: Lujia Chen, Han Zhang, Binfeng Lu, Gregory F. Cooper, Anwaar Saeed, Xinghua Lu
Journal: Journal of Clinical Oncology (2024)

59 Background: Colorectal cancer (CRC) is the 3rd most common cancer. The consensus molecular subtypes among CRC tumors reflects the heterogeneity of composition and functional states of cells in the tumor microenvironments (TME), which in turn may underlie diverse behaviors of disease progression and responses to anticancer treatments. Cells within a TME communicate through intricate cell-cell communication (CCC) networks. The altered state of one cell can influence the states of other cells through ligand-receptor-mediated signal transduction. Gaining insight into the cellular states of cells and understanding their complex communications in a TME is vital for uncovering the heterogeneous mechanisms governing tumor growth, immune evasion, and therapy resistance. Methods: In this meta-analysis of eight single-cell cohorts encompassing 153 patients and 279 samples with more than 600,000 cells, we advance the understanding of CCC networks in CRC through a novel analytical framework. Employing hierarchical language modeling, we identify gene expression modules (GEMs) that mirror single-cell signaling states, crucial for deciphering the complexity of intercellular interactions. By applying causal discovery methods, we systematically uncover GEMs likely regulated by ligand-receptor signaling and cross-cell-type communication. We further validate the discovered CCC using spatial transcriptomic data by testing the spatial co-localization. Results: This analysis reveals nine cross-cell-type CCC programs, marked by highly correlated GEMs across various cell types, shedding light on the intricate CCC networks within the TME. The discovered CCC programs include malignant program, proliferation program, stromal interactions, stromal-myeloid interactions, innate immunity interactions, regulatory interactions, epithelial-lymphocyte interactions and exhaustion program. Each program is composed of GEMs from various cell types. Spatial transcriptomics further validate these findings by demonstrating the co-localization of GEMs within CCC programs in distinct spatial domains, emphasizing the spatial dynamics of tumor intercellular communication. We successfully construct the CCC subnetworks connected by ligand-receptor signaling. Our interactive website and analytical framework equip researchers with powerful tools to explore complex mechanisms, potentially uncovering novel drug targets and refining strategies for precision immunotherapies. Conclusions: This study provides an in-depth analysis of colorectal cancer by: 1) Cataloging GEMs that precisely depict the transcriptomic processes unique to individual cell clusters or shared among multiple cell clusters. 2) Presenting the CCC networks driven by ligand-receptor interactions within the TME supported by both single-cell RNA-seq data and spatial transcriptomic data.