bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective analysis of change in frequency of STK11 mutation in lung adenocarcinomas over a 10-year period.
Authors: Parekh Deevyashali , Basnet Alina , Pavlick Dean , Ross Jeffrey S. , Graziano Stephen L. 
Published: June 2024

8032 Background: Previous studies have linked the presence of inactivating mutations in the tumor suppressor gene STK11 with reduced efficacy of immune checkpoint inhibitor (ICI) treatments in lung adenocarcinoma (LA). We queried whether there has been a change in the STK11 mutation frequency over the last 10-year period that could potentially reflect the emergence of additional acquired resistance mutations. Methods: Over a 10-year period from 2013 through 2022, 109,763 clinically advanced LA underwent hybrid capture based comprehensive genomic profiling (CGP) to assess all classes of genomic alterations (GA) at a single reference laboratory (Foundation Medicine). MSI-high status and tumor mutational burden (TMB) were determined from the sequencing data. PD-L1 status was measured by immunohistochemistry (IHC) using the Dako 22C3 kit with TPS scoring. Statistical comparisons utilized the 2-tailed Chi Square method with the Yates’ correction. Results: The frequency of STK11 inactivating GA in all cases of LA significantly increased during the study period from 2013 to 2022 (16.1% vs 20.1%; p=0.0005). This increase appeared to be predominantly in KRAS wild type LA (10.1% vs 15.5%; p<0.0001). The STK11 GA frequency slightly declined in the KRAS mutated LA over the 10-year period (29.9% vs o 27.0%, P=0.25). During the same time period, the KEAP1 GA frequency increased from 12.6% to 14.9% (p= 0.076) and the frequency of combined STK11 and KEAP1 GA increased from 4.8% to 8.0% (p=.0006). The frequencies of MSI-high status, TMB and PD-L1 expression did not significantly change over the observation period. Conclusions: The continuously increasing approved indications for ICI-based treatments for both early stage and clinically advanced LA appears to be accompanied by a significant increase in the frequency of inactivating STK11 GA predominantly in the KRAS mutation negative LA population. This inactivation is associated with an attenuated response rate and progression-free survival in this population. Given the development of novel therapies focused on potential restoration of STK11 function by HDAC/CoREST inhibition, further study of the STK11 GA distribution in LA appears warranted. [Table: see text]
Differentially expressed microRNAs in prediagnostic serum linked to lung cancer up to eight years before diagnosis in prospective, population-based cohorts: A HUNT study.
Authors: Nguyen Olav Toai Duc , Fotopoulos Yannis , Nøst Therese Haugdahl , Markaki Maria , Lagani Vincenzo , Sætrom Pål , Tsamardinos Ioannis , Røe Oluf Dimitri D. 
Published: June 2024

8041 Background: With lung cancer incidence and mortality on the rise, blood biomarkers are increasingly in demand for early detection. The aim of this study is to discover and validate novel biomarkers based on next-generation sequencing performed on blood samples from non-cancer, ever-smokers up to eight years prior to diagnosis. Methods: Initial consideration was given to serum samples from the population-based prospective HUNT2 and HUNT3 cohorts, age > 18 (n = 98,737). Inclusion criteria for cases were ever-smokers, no prior cancer at study entry, and 0–8 years between blood sampling and lung cancer diagnosis in the discovery and 0-4 years in the validation cohort. Among future cases, equal numbers of adenocarcinoma, squamous cell carcinoma and small-cell lung carcinoma were included. Every subsequent case of lung cancer had a matched control, ratio 1:1. The controls were matched for sex, age at study entry, pack-years, smoking cessation duration, comparable HUNT Lung Cancer Model risk score and no cancer diagnosis until the end of the study. The total number of serum samples included in the discovery and validation dataset were 240 (from HUNT2) and 72 (from HUNT3), respectively. The samples were analyzed by genome-wide small RNA seq (Illumina). Results: When we contrasted all cases against all controls, nine differentially expressed microRNAs with AUC > 0.60 (FDR < 0.25) and total raw count of > 0.5 appeared in common in the discovery and validation datasets. Among these, three microRNAs were associated with non-small cell metastatic with mean AUC of 0.65 and 0.76 in the discovery and validation datasets, respectively. Furthermore, the signature of these three microRNAs in combination reached an AUC of 0.75 (discovery) and 0.90 (validation). Conclusions: Up to eight years before diagnosis, a small number of substantially differentially expressed microRNAs were found in serum. These intriguing microRNAs can potentially function as early diagnostic indicators for lung cancer, either alone or in combination. Further investigation and validation of these results in a larger prospective serum dataset are required.
Comprehensive analysis of predictive factors for efficacy in concurrent chemo-radiotherapy for locally advanced non-small cell lung cancer, utilizing individual patient data from the Japan lung cancer society integrated clinical trial database: Is there room for further improvement?
Authors: Ozawa Yuichi , Yamamoto Kouji , Sugawara Shunichi , Niho Seiji , Ohe Yuichiro , Okamoto Hiroaki , Hotta Katsuyuki , Ikeda Norihiko , Yamamoto Nobuyuki 
Published: June 2024

8043 Background: The standard treatment for unresectable, locally advanced NSCLC is concurrent chemoradiotherapy followed by durvalumab. While the effectiveness of chemoradiotherapy is pivotal, the exploration into predictive factors of the efficacy is notably limited. Methods: The Japanese Lung Cancer Society (JLCS) integrated eight randomized Phase II/III trials (JCOG9812, JCOG0301, NJLCG0601, OLCSG0007, SPECTRA, TORG1018, WJOG5008L, WJTOG0105) concerning chemoradiotherapy for locally advanced NSCLC, constructing the JLCS Integrated Clinical Trial Database (JIDB), with individual data of 1288 patients. This study analyzed 1162 patients who underwent concurrent chemoradiotherapy, focusing on factors impacting PFS. A logistic regression with the least absolute shrinkage and selection operator (LASSO) analyses for 3-yr PFS were performed, and the five most related factors were further evaluated using the Kaplan-Meier method and log-rank tests. The impact of pneumonitis and esophagitis on PFS was also explored. Results: Age [median (Q1;Q3)]; 64 (57;71), male/female; 961/201, Ad/Sq/Oth; 580/446/134, PS 0/1/2; 562/578/5, stage IIIA/IIIB; 468/694, T factor 4/3/2/1/0; 436/158/341/156/3, N factor 3/2/1/0; 300/692/44/62, PS 0/1/2; 562/578/5, primary site; upper, middle/lower lobe; 599/161, BMI; 21.8 (19.7;24.0), weight loss (≥5% within 6m) yes/no; 135/644, LDH (IU/l); 203 (175;276), CRP (mg/dl); 0.70 (0.20;2.60), irradiated dose (Gy); 60 (60;60), combined regimen; platinum/taxane 303, CDDP/mitomycin/vindesine; 254, CDDP/5-FU-based; 196, CDDP/vinorelbine 87, CDDP/pemetrexed 50, others 272. The median PFS in all patients was 9.72m (95% CI; 9.33 – 10.38), with 3-yr, 5-yr, and 10-yr PFS rates of 19.7, 14.3, 10.1%. LASSO logistic regression identified Sq, lower lobe primary, age, pack-years, and weight loss as the top negative influencers. The PFS curve was significantly shorter in patients with lower lobe primary (median of 8.15 vs. 9.46m, p = 0.023) and weight loss (median of 7.29 vs. 9.72m, p < 0.0001). Pneumonitis occurred in 50.9% (grade≥3 in 6.7%) and esophagitis in 41.9% (grade≥3 in 3.9%). Grade≥2 pneumonitis shortened PFS (8.2 vs. 10.2m, p = 0.00015), while, unexpectedly, grade≥1 esophagitis was associated with longer PFS (12.9 vs. 8.6m, p < 0.0001). Conclusions: The efficacy of concurrent chemoradiotherapy varies significantly based on the primary site. Weight loss is a significant predictor of efficacy, as is in metastatic disease. The impact of pneumonitis and esophagitis suggest that modifying lung and esophageal irradiation might enhance treatment efficacy. Further research in this area is still certainly warranted.
Biomarker testing in early-stage NSCLC: Results from the MYLUNG Consortium.
Authors: Evangelist Makenzi Colleen , Butrynski James Edward , Paschold John C. , Ward Patrick J. , Waterhouse David Michael , Spira Alexander I. , Ali Kashif , Hakimian David , Jotte Robert M. , Larson Timothy , Meshad Michael W. , Owera Rami , Richards Donald A. , Neubauer Marcus A. , Robert Nicholas J , Yori Jennifer L. , Pant Manoj , Coleman Robert L. , Spigel David R. 
Published: June 2024

8047 Background: The Molecularly Informed Lung Cancer Treatment in a Community Cancer Network: A Pragmatic Consortium (MYLUNG) program seeks to identify and resolve barriers to biomarker testing in patients (pts) with non-small-cell lung cancer (NSCLC). We previously reported prospectively collected molecular testing data in pts with Stage IB-IV NSCLC (Evangelist et al. 2023). Herein we report additional data on molecular testing rates and patterns in the cohort of pts with early-stage (ES) NSCLC. Methods: Pts were enrolled from 12/20-9/22 at 18 community practices (76 sites) across the US Oncology Network. Analyses performed in the ES cohort include rates of molecular testing for targets with approved (PD-L1 , EGFR) or emerging ( ALK) therapies for ES NSCLC and next-generation sequencing (NGS); reasons for not testing; and treatment (Tx) received, including targeted therapy and immunotherapy (IO). Analyses are preliminary as data collection continues over 5-year follow-up. Results: Included in this analysis were 284 pts with newly diagnosed Stage IB-IIIA NSCLC: median age 68y (range 32, 92); 50% female; 54% ECOG 0-1; 61% adenocarcinoma, 36% squamous cell carcinoma. In total, 76% of pts (82% of pts with adenocarcinoma vs 67% with squamous cell carcinoma) had molecular testing ordered prior to or within 12 weeks of initiating first systemic therapy. Rates of testing (either alone or inclusive of other tests) were PD-L1 ,74%; EGFR,71%; ALK, 62%; EGFR + PD-L1, 61%. In total, 52% of pts had NGS testing; overall, 16% received no molecular testing. The most common reasons for not testing were patient and/or provider attitude/perception (34%) and insufficient tumor tissue (25%). Conclusions: New therapeutic options provide a catalyst to increase molecular testing in ES NSCLC. EGFR and PD-L1 testing are now standard for the management of these pts, with other biomarkers emerging. In this study, 54% of pts received testing for PD-L1, EGFR, and ALK, with additional therapy being offered in pts with biomarker-positive tumors; however, 16% still received no molecular testing at all. For pts with EGFRwt/PD-L1+ tumors, prescription of IO increased 1.8-fold post-adjuvant FDA approval. Data from this and future analyses will be used to implement interventions to improve molecular testing rates in NSCLC. [Table: see text]
Outcomes of combined immunotherapy and palliative radiotherapy in patients with recurrent/metastatic head and neck cancers.
Authors: Cheng Yanshuang , Wang Juan , Sun Ji , Zhong Yahua , Wu Qiuji 
Published: June 2024

e18002 Background: Immunotherapy has revolutionized the treatment for recurrent/metastatic head and neck cancers (R/M HNC). It is uncertain whether the combination of immunotherapy and radiotherapy can provide survival benefits for R/M HNC. Methods: This study included patients with R/M HNC who underwent immunotherapy in our institute from November 2018 to October 2022. All patients received intravenous PD-1 inhibitors every 3 weeks. Palliative radiotherapy was administered to localized lesions for symptomatic treatment purposes in addition to systemic therapies. Tumor response was evaluated using RECIST1.1 criteria. The primary outcome measures were progression-free survival (PFS) and overall survival (OS). Other outcome measures were disease control rate (DCR) and objective response rate (ORR). The Kaplan-Meier method was utilized for survival analysis, and univariate and multivariate Cox regression analysis was conducted to identify prognostic factors associated with PFS and OS. Results: We included 129 R/M HNC patients. The median follow-up time was 14.0 months. The median number of immunotherapy courses received was 4 (range: 1-60). During immunotherapy, 43 patients received palliative radiotherapy, targeting primary tumors, lymph nodes, metastasis in liver, lung, bone, and other sites. Following the treatments, 16 (12.4%) patients achieved complete response (CR), 44 (34.1%) achieved partial response (PR), 35 (27.1%) had stable disease (SD), and 34 (26.4%) had progressive disease (PD). The ORR was 46.5% and the DCR was 73.6%. The group receiving immunotherapy combined with palliative radiotherapy had higher ORR (65.1% vs 37.2%, p = 0.005) and DCR (90.7% vs 65.1%, p = 0.004) than those without palliative radiotherapy. The PFS (15.0 months vs 4.0 months, p = 0.0027) and OS (not reached vs 26.0 months, p = 0.036) were improved in patients receiving palliative radiotherapy compared to those not. Patients who had received prior radiotherapy (n = 81) had a shorter PFS (4.0 months vs 14.0 months, p = 0.014), while there was no difference in OS (p = 0.16). We further showed that patients had better PFS (20.0 months vs 2.0 months; p < 0.0001) and OS (43 months vs 17 months; p = 0.0043) when they received more than 4 cycles of immunotherapy. At the same time, our findings demonstrated that immunotherapy combined with nanoparticle albumin‐bound (nab-) paclitaxel-based regimens may prolong PFS (14.0 months vs 4.0months vs 2.5months, p = 0.0055) than gemcitabine-based regimens and other regimens. Conclusions: In patients with R/M HNC, the combination of immunotherapy and palliative radiotherapy demonstrates a synergistic effect, resulting in survival benefits. Prior radiotherapy might compromise patients’ PFS. Increasing the number of immunotherapy cycles and combining with nab-paclitaxel chemotherapy may improve patient survival.
Real-world evaluation of nivolumab in patients with non-nasopharyngeal recurrent or metastatic head and neck cancer: A retrospective multi-center study by the Turkish Oncology Group (TOG).
Authors: Akyildiz Arif , Guven Deniz Can , Koksal Baris , Karaoğlan Beliz Bahar , Kivrak Salim Derya , Sütcüoğlu Osman , Erciyestepe Mert , Alan Ozkan , Taban Hakan , Yildirim Nilgun , Sakalar Teoman , Yazilitas Dogan , Ismayilov Rashad , On Sercan , Aslan Ferit , Demirci Nebi Serkan , Kemal Yasemin , Diker Omer , Gullu Ibrahim Halil , Aksoy Sercan 
Published: June 2024

e18004 Background: Head and neck cancers (HNCs) represent a significant global health concern due to high morbidity and mortality rates. The prognosis for advanced or recurrent cases remains challenging. Nivolumab obtained approval for recurrent or metastatic HNC based on the Phase III CheckMate 141 trial. This study aimed to evaluate the real-world outcomes of nivolumab in patients with non-nasopharyngeal HNC. Methods: In this multicenter retrospective study, we analyzed 124 patients with recurrent or metastatic non-nasopharyngeal HNC who received nivolumab in the second-line setting and beyond. Data were collected from 22 different cancer centers across Turkey. The effectiveness and safety of the treatment and survival outcomes were evaluated. Results: The median follow-up duration was 7.5 months (3-66.1 months). Overall survival (OS) and progression-free survival (PFS) were determined to be 11.8 and 3.8 months, respectively. Nivolumab exhibited clinical responses, yielding an objective response rate (ORR) of 29.9% and a disease control rate (DCR) of 55.7%. Safety assessments consistently revealed a well-tolerated profile, with no reported instances of treatment discontinuation or mortality attributed to adverse side effects. Notably, several factors, including performance status, neutrophil-to-lymphocyte ratio, tumor location, and p16 positivity, emerged as prognostic indicators significantly associated with OS. Conclusions: Nivolumab is an effective and safe treatment option for patient with recurrent or metastatic non-nasopharyngeal HNC in real-world setting. [Table: see text]
Prevalence and risk factors associated with chronic pain among survivors of head and neck cancer.
Authors: Jiang Rong , Chen Meng , White Melissa Christina , Ramos Katherine , Corbett Cheyenne , Watts Tammara L , Graboyes Evan Michael , Osazuwa-Peters Nosayaba 
Published: June 2024

e18016 Background: There are over 500,000 survivors of head and neck cancer (HNC) in the United States. Pain is one of the most common symptoms of HNC due to disease anatomy, treatment and post-treatment toxicities. While opioid treatment is a mainstay in HNC care, factors associated with chronic pain are not properly understood. Methods: We built a retrospective cohort of adult patients with a history of HNC using the National Health Interview Survey (NHIS) from 2010 to 2021 that collected through personal household interviews ( n = 353). Chronic pain was defined using the question: In the past three months, how often did you have pain? Would you say never, some days, most days, or every day? Chronic pain was coded as “yes” if the response was most or every day, and “no” if it was never or some days. Using weighted logistic regression analysis adjusting for age and sex, we examined the association between chronic pain and sociodemographic (race, insurance, education, income, employment and smoking history) and clinical (depression, and self-rated health status) factors. Results: Among individuals with a history of HNC, 149 (adjusted Prevalence Rate = 43.2%; 95% CI: 36.6%, 49.8%) had experienced chronic pain in the past three months. There were significant associations with clinical factors, as individuals with poor self-rated health (aOR = 6.42; 95% CI: 3.25, 12.70) and those with depression (aOR = 3.25; 95% CI: 1.73, 6.11) had increased odds of reporting chronic pain. Among sociodemographic factors White race (aOR = 2.52, 95% CI: 1.04, 6.10) and Medicaid insurance (aOR = 3.76, 95% CI: 1.40, 10.10) were associated with and increased odds of reporting chronic pain. There was no significant association of education, income, employment or smoking history with chronic pain among the study HNC survivors. Conclusions: Over 40% of individuals with a history of HNC may be living with chronic pain, unequally distributed based on race, payor status and comorbid depression. Given the current opioid crisis in the United States, and the poor outcomes associated mental health in cancer survivors, our findings highlight clinical and social determinants of health factors that should be taken into the consideration for management of chronic pain among survivors of HNC patients.
Prognostic impact of caspase-8 mutation in oral cavity squamous cell carcinoma: A real-world cohort study.
Authors: Lu Hsueh-Ju , Wu Ming-Fang , Yang Sung-Fa 
Published: June 2024

e18029 Background: Identifying the drive genes and inhibiting its significant signals were persistently the main concept in cancer treatment. However, for oral cavity squamous cell carcinoma (OCSCC), the most influential genes for overall survival (OS) remain unclear. Methods: A total of 120 OCSCC patients, with corresponding pathologic specimens at initial diagnosis, were collected in Taiwan. After excluding eligible patients, 95 patients were enrolled for analysis. Whole-exome sequencing was done and the prognostic impact of each gene was analyzed. The Cancer Genome Atlas (TCGA) database was used to validate. Results: The incidences of caspase-8 mutation were 22.1% and 10.9% in the Taiwan and TCGA cohort, respectively. In the Taiwan cohort, caspase-8 mutation was the most significant independent for OS with an adjusted hazard ratio (HR) [95% confidence interval (CI)]: 3.83[1.84-7.99]). It was validated by the TCGA database (HR [95% CI]: 1.51[1.00-2.29]). The 5-year OSs of the patients with or without caspase-8 mutation were 38.1% vs. 75.3% ( P < 0.001) (HR [95% CI]: 3.264[1.645-6.438]) in the Taiwan cohort, and 26.1% vs. 49.0% ( P = 0.048) (1.513[1.001-2.288]) in the TCGA cohorts, respectively. Caspase-8 mutation was also individually associated with poor prognosis for TNM stage I/II/III/IV, respectively. L81F, R127*, R472*, R494*, S174*, and T528I were the intersected point mutations of caspase-8. Most of these intersected point mutations were pathologic/likely pathologic variants in the published bioinformatic databases. Conclusions: In conclusion, caspase-8 mutation was the most significant genetic alteration impacting prognosis. Novel agent development could be considered for this candidate.
Differential gene expression and methylation of upper aerodigestive tract and lung squamous cell carcinoma between European ancestry (EA) and African ancestry (AA) patients.
Authors: Thomas Hannah , Mukhina Vera , Saxena Anirudh , Mehra Ranee , Gaykalova Daria 
Published: June 2024

e18031 Background: Pan-cancer analysis of cancer disparities revealed both head and neck and lung cancer are among the top cancers with significant disparities in overall survival outcomes between EA and AA patients. Analysis of The Cancer Genome Atlas (TCGA) for all cancer in EA and AA found genetic signatures associated with noted disparities, such as somatic copy number alterations, TP53 mutations, CCNE1 amplification, and overexpression of genes correlated with chromosomal instability. To inform whether epigenetic and transcriptomic factors could be driving the disparities seen in squamous cell carcinoma (SCC) of the upper aerodigestive tract (UADT) and lung, we sought to analyze genomic data to identify differentially methylated and expressed genes between EA and AA patients and determine whether these affected survival. Methods: TCGA was queried to extract data from self-identified EA and AA patients with head and neck, esophageal, and lung SCC. Literature suggests that SCC tumors share genetic and epigenetic signatures and can be analyzed as a group. Human papillomavirus positive patients were excluded. Patients were separated into EA and AA groups matched for age, stage, and smoking to account for clinical biases of biological analysis. DNA methylation (Epic array) and gene expression (RNA-Seq) profiles were compared between tumor tissue samples in EA patients, tumors in AA patients, and normal tissue. The genes that were identified to be differentially methylated were then analyzed to compare overall survival between hypomethylation and hypermethylation of each identified gene, with and without subgrouping by race. Differentially expressed genes were similarly analyzed between high and low expression. Overall survival was estimated by the Kaplan-Meier method and compared using the log-rank test. Results: A comparison of DNA methylation profiles found 79 genes that were differentially methylated when comparing EA tumor, AA tumor, and normal tissue samples. Survival analysis was performed on top 21 of the differentially methylated genes. Of these, 9 were found to have significant differences in overall survival when stratifying by race and methylation status. Differentially methylated genes included MAD1L1 (Mitotic Arrest Deficient 1 Like 1), which is known for its role in the spindle assembly checkpoint in mitosis and tumor suppression. Similar analysis revealed 404 genes that were differentially expressed comparing EA tumor, AA tumor, and normal tissue. Candidate genes based on expression level will be discussed. Conclusions: Differential DNA methylation and gene expression were noted between EA and AA groups with lung and UADT SCC. This difference may contribute to the disparity in overall survival seen between these groups that persists even when controlling for variables commonly associated with worse survival.