bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between patient-reported nutritional status, survival, and toxicity among patients with limited stage small-cell lung cancer (LS SCLC) in a randomized trial of high-dose, twice-daily (BID) thoracic radiotherapy (TRT).
Authors: Taranova Evgenia , Gronberg Bjorn H. Henning , Halvorsen Tarje Onsøien , Killingberg Kristin Toftaker , Slaaen Marit , Aanerud Marianne 
Published: June 2023

8519 Background: Up to 1/3 of LS SCLC patients are cured by chemoradiotherapy (CRT), but severe toxicity is frequent and population-based studies show that many patients do not receive standard CRT. More knowledge on how to predict who experiences side-effects or achieves long term disease control is needed. Poor nutritional status is strongly associated with inferior survival in many types of cancer including non-small cell lung cancer, but little is known about whether this is the case in LS SCLC. We investigated whether nutritional status reported by patients on the Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF) was associated with toxicity and survival among participants in a trial comparing high dose with standard dose twice-daily TRT in LS-SCLC (NCT02041845, n=170). Methods: Patients received four courses of platinum/etoposide chemotherapy and were randomized to TRT of 60 Gy/40 fractions or 45 Gy/30 fractions. Patients completed PG-SGA SF before treatment commenced and were categorized as having low (PG-SGA SF score 0–3.9), intermediate (4.0–8.9) and high (≥9) risk of malnutrition. Toxicity was graded according to CTCAE 4.0. Median follow-up for survival was 49 months. Results: 113/170 (66.5%) patients completed PG-SGA SF at baseline. Median age was 65 years, 46.0% were men, 88.5% had PS 0-1, 87.6% stage III disease and 22.1% weight loss of >5% the three months before inclusion. Median PG-SGA SF score was 3.0, 52.2% of patients had low, 29.2% intermediate, and 18.6% high risk of malnutrition. Numerically, there were more patients with stage III, PS 1-2 and pleural fluid among those at high risk. There was no difference in mean no. of chemotherapy courses (low: 3.85, intermediate: 3.88, high: 3.90, p=0.95) or TRT completion (low: 96.6%, intermediate: 97.0%, high: 95.2%, p=1.0). There were no statistically significant differences in proportions who experienced grade 3-4 toxicity (low: 88%, intermediate: 91%, high: 86%, p=0.86), median PFS (low: 15.1 months, intermediate: 11.8 months, high: NR, p=0.23), 2-year survival (low: 68%, intermediate: 52%, high: 67%, p=0.28) or median OS (low: 38.1 months, intermediate: 25.8 months, high: NR, p=0.15). Patients with weight loss >5% did not experience more grade 3-4 toxicity (92% vs. 87%, p=0.73), had similar median PFS (24.0 vs. 15.9 months, p=0.69), 2-year survival (64.0% vs. 66.2%, p=0.84) and median OS (30.6 vs. 35.1 months, p=0.93) as those without. Conclusions: Our study suggest that LS SCLC patients tolerate and should receive concurrent chemotherapy and twice-daily TRT regardless of nutritional status and weight loss.
A study of tumor neoantigen burden and HLA-LOH by whole-exome sequencing to characterize immune biomarkers of lung cancer.
Authors: Wang Wei , Liao Wenting , Zhen Baoling , Ji Tianrong , Du Chen , Cheng Shaochen , Chen Yaru , Yang Jie 
Published: June 2023

8527 Background: Lung cancer is a leading cause of cancer-related death worldwide. Precision immunotherapy, such as the use of immune checkpoint inhibitors (ICIs), has been shown to improve the survival of lung cancer patients. Cancer cells with high amount of neoantigens are more likely to be captured by immune cells and thus patients with high Tumor Mutation Burden(TMB) and high Tumor Neoantigen Burden(TNB) are estimated to be prone to ICIs treatment. HLA class Ⅰ is one of the main factors affecting the prognosis of ICI in treatment. Studies have indicated that patients with highly heterozygous HLA-I are more likely to have better responses to ICI treatment. Some specific HLA-Ⅰ genotypes and somatic mutations can affect the prognosis of ICIs treatment. Methods: In this study, we performed whole-exome sequencing (WES) of 200 pairs of tumor and gDNA samples from lung cancer patients. Tumor sample comes from tumor tissue or paraffin-embedded tissue and gDNA is extracted from white blood cells from peripheral blood. We analyze the WES data to obtain the TMB and HLA types of each sample. Then the peptide affinity of MHC-I genes were quantified based on IC50(nM) by netMHCpan software, and the level of neoantigen affinity were classified as strong (IC50≤50nM), weak (50nM < IC50≤500nM), and negative (IC50 > 500nM). TNB is defined as the number of high- affinity neoantigens per megabase of interrogated genomic sequence. Then we conducted linear regression analysis to study the statistical relationship between TMB and TNB. Finally, we analyzed the LOH status at the major region of HLA (HLA-A, HLA-B, and HLA-C) and classified the individuals who have LOH at all three types of HLA as HLA-LOH strong positive, samples with one or two LOH among the three HLA types as weak positive, and samples have no LOH are classified as HLA-LOH negative. Results: Among the 200 samples, the median value of TMB and TNB is 3.25 Muts/Mb and 1.09 Neos/Mb, respectively. 8.5% of the sample have high TMB(TMB≥10). TMB and TNB are also significantly positively correlated (p-value < 0.0001). For HLA typing, 82.0% HLA-A, 96.0% HLA-B, and 92.5% HLA-C are heterozygous. The dominant HLA types are: (A*11:01), (A*02:01), (B*46:01), (B*40:01), (C*01:02), and (C*07:02). As for LOH status among the three HLA types, 14.57% of the individuals are HLA-LOH strong positive, 31.66% are HLA-LOH weak positive, and 53.77% of the samples are HLA-LOH negative. Lastly, the average numbers of detected high-affinity neoantigens are statistically significantly related to the occurrence of HLA-LOH (Analysis of Variance p-value < 0.01). Conclusions: HLA-LOH occurs in nearly half of our lung cancer samples, and it is associated with TMB-High and TNB-High. The analysis of HLA-LOH refines the prediction of neoantigen and gain understanding of drug resistance and immunotherapy.
Prevalence of EGFR mutations in patients with resected stage I-III non-squamous NSCLC: Results from the EARLY-EGFR study.
Authors: Soo Ross A. , Reungwetwattana Thanyanan , Perroud Herman Andres , Batra Ullas , Kilickap Saadettin , Gallegos Luis Fernando Tejado , Donner Natalia , Alsayed Mohamed , Huggenberger Reto , Dao Tu Van 
Published: June 2023

8531 Background: The prevalence of EGFR mutations ( EGFRm) in resected stage I-III NSCLC remains controversial as prior research studies were retrospective in nature. EARLY-EGFR is the first prospective, international study to determine the prevalence of EGFRm and treatment patterns in patients (pts) with early-stage NSCLC. Methods: EARLY-EGFR (NCT04742192), a non-interventional real-world study, captured data on EGFRm status, treatment patterns, demographic, clinical and pathological characteristics in consecutively enrolled pts with surgically resected stage IA-IIIB (AJCC 8th) non-squamous NSCLC (Mar 2021 – Oct 2022). The primary endpoint was prevalence of EGFRm and secondary endpoints included prevalence of EGFRm subtypes and treatment patterns. Results: Of 601 pts (median [range] age: 62 [30-86] yrs) enrolled at 33 centers across Middle East and Africa (n=16), Latin America (n=80), and Asia (n=505), 317 (52.7%) were females, 354 (58.9%) were never smokers. The majority had stage IA-IB NSCLC (64.1%) involving right lung (62.9%), no nodal involvement (81.5%), T1a-T2b tumor (82.7%), adenocarcinoma histology (98.7%), and 105/420 (25.0%) tumors were poorly differentiated. About 23.3% (130/559) were diagnosed through a screening program; 60/539 (11.1%) reported family history of lung cancer. The overall prevalence of EGFRm was 50.7% (300/592). Exon-19 deletions accounted for 50.3%, L858R mutations for 35.7%, and compound mutations for 2.3% of mutations. EGFRm tumors were found to be PD-L1 positive in 38.5% of cases (15/39). Women had higher EGFRm rate than men (63.6% vs 36.2%). Compared with EGFR wild type (wt), pts with EGFRm were more likely to be never smokers (39.5% vs 60.5%) and have stage I/II NSCLC (46.5% vs 53.5%) (Table). Of 216 stage II/III NSCLC pts, only 51.4% received systemic adjuvant therapy. Significantly higher EGFRm rates in stages I and II than in stage III NSCLC (p<0.001 and p=0.050) were found, while no significant difference was found between stages I and II NSCLC (p=0.158). Conclusions: In this first prospective, real-world study of EGFRm prevalence in resected NSCLC, stage III and smoking were independent predictors associated with decreased odds of EGFRm. The results highlight the need to adhere to ASCO adjuvant chemotherapy guidelines, as only half of stage II/III NSCLC pts received adjuvant systemic therapy. Clinical trial information: NCT04742192 . [Table: see text]
Multi-genomic analysis of compound and uncommon EGFR mutations in patients with non-small cell lung cancer.
Authors: Park Jayoung , Lee Yu Min , Ka Sojeong , Kim Seoree , Kim In-Ho , Sung Yeoun Eun , Jung Chan-Kwon , Shin Jung-Young , Chun Sang Hoon , Lee Young Ho , Kang Jin Hyoung , Kim Joori 
Published: June 2023

8534 Background: There are similar and different properties between the epidermal growth factor receptor mutations (mEGFR), which are classified into common, uncommon, and compound mutation subtypes depending on their location and pattern on the EGFR gene. We investigated the RWD and RNA expression profile of uncommon and compound mutations in the mEGFR+ NSCLC patients. Methods: We collected the medical information for stage I-IIIA mEGFR+ NSCLC patients receiving curative surgical resection in Seoul St. Mary’s Hospital. We explored the RNA expression profile using multiplex IF and High-Plex Digital Spatial Profiling. A total of 18,676 DEG libraries were constructed, and 151 significance genes with > 2-fold changes, 4-log 2 normalized read counts, and p-value = 0.05 (up and down) were identified. Results: In hospital cohort, 941 mEGFR+ cases of total 6,609 cases consist of common, 860 (91.4%), uncommon, 60 (7.4%), and compound, 21 (2.2%). Median relapse-free survival in uncommon and compound mEGFRs (31.4M and 33.7M) was shorter than common mEGFRs (40.1M, p = 0.877), but median overall survival did not differ between the groups. CNS recurrence rates in the uncommon and compound mEGFRs (40.0% and 35.3%) tended to be higher than that of common mEGFRs (27.4%, p = 0.361). Spatial RNA-seq data of the ratio of deconvolution individual cells showed that genes involved in inflammatory and immune response were relatively lower in mEGFR+ groups. According to the difference in DEG library through clustering heat map, uncommon or compound mEGFR in the immune, inflammatory response category, extracellular matrix, RNA splicing gene category, JAK-STAT, p53, PI3K-AKT, and notch signaling pathway related genes were down regulated compared to common mEGFR+ group. Gene ontology string analysis revealed RNA expression of genes in compound mEGFR was functionally associated with chemokine production (23.4%), electron transfer activity (14.9%) and T cell selection (8.5%), and, in uncommon mEGFRs, was associated with regulation of oligopeptide transport (26.1%), hypermethylation of CpG island (21.7%), and CD4+ CD25+ αβ regulatory T cell lineage commitment (13.0%), compared to common mEGFR+ groups. Based on the GSEA, relatively highly clustered genes in compound mEGFR were the protein modification process, G-protein coupled receptor, regulation of cytosolic calcium ion concentration, and IL-5 production pathways, and lower ES levels in oxidative phosphorylation and RNA processing pathways, when compared to common mEGFR+ groups. Conclusions: In conclusion, our results suggest that uncommon and compound mEGFR+ subtypes exhibiting distinguished RNA expression profile of functional signaling pathways and protein network be not same disease entity as common mEGFR+ subtype.
Real-life efficacy of nivolumab plus ipilimumab combination in untreated, unresectable malignant pleural mesotheliomas: Result of French early access program—MESOIMMUNE – GFPC 04-2021.
Authors: Bylicki Olivier , Guisier Florian , Daniel Catherine , Swalduz Aurélie , Grolleau Emmanuel , Bernardi Marie , Hominal Stephane , Cloarec Nicolas , Deshayes Simon , Raimbourg Judith , Veillon Remi , Oulkhouir Youssef , Audigier-Valette Clarisse , Gobert Aurélien , Falchero Lionel , Thibonnier Lise , Chasseray Matthieu , Raynaud-Donzel Christine , Decroisette Chantal , Greillier Laurent 
Published: June 2023

8536 Background: The SOC for unresectable malignant pleural mesothelioma (MPM) has changed in 2020 with the combination nivolumab plus ipilimumab (NIVO+IPI) results of CheckMate 743 study. As CheckMate 743 was therapeutic trial in selected MPM patients (pts), additional data would be of interest to confirm the results in real-life setting. Methods: The present multicenter, retrospective study assessed the outcomes of NIVO+IPI, via an early access program (EAP) in France, in pts with treatment naïve unresectable MPM. The primary objective was investigator-assessed real world progression-free survival (rwPFS) from initiation of NIVO+IPI, defined as time from first dose of NIVO+IPI to first documentation of objective disease progression or death from any cause. The secondary objectives were real world OS (rwOS), objective response rate (ORR), and safety of NIVO+IPI combination. Results: From April 1, 2021 to Feb 15, 2022 (last day of EAP) there were 143 pts included out of 350 pts treated by EAP for unresectable MPM in 44 centers. Population characteristics are described in the table. With a median follow-up of 14.1 months, median rwPFS was 7.8 months (95%CI 6.2-9.5). rwPFS rates no differ according to histological subtypes: rwPFS for epithelioid MPM was 8.1 months (95%CI 6.0-12.6) and 7.4 months (95% CI 5.3-11.2) for other histological subtypes. The median rwOS was not reached (NR), 1-year survival rate was 65% (95% CI 57-75%). Median rwOS was NR and 13.1 (95% CI 7.8- NA) in epithelioid and non-epithelioid MPM, respectively. At 1 year, 71.2% of pts with epithelioid MPM are still alive versus 51.2% in pts with other histological subtypes. ORR was 23.9% (95% CI 16.9-32.0%) with median time to response of 3.68 months (2.33-5.09) after introduction of NIVO+IPI. Disease control rate was 80.4%. Grade 3-4 adverse events (AE) occurred in 37.8%. Severe immune-related AE occurred in 13.9% of patients. Five deaths were associated with treatment-related AEs according to investigators judgment. Conclusions: While pt’s characteristics differed from the pivotal trial, notably with older and unselected patients, efficacy outcomes that we observed here compares favorably with CheckMate 743 results. Tolerance looks acceptable in real-life setting despite 5 toxic deaths reported. Extended follow-up of our cohort will allow consolidation of the results. Clinical trial information: NCT05308966 . [Table: see text]
Long-term outcomes of single and five fraction schedules of stereotactic body radiation therapy for early-stage central or peripheral NSCLC: Neither fractionation nor location matter?
Authors: Huang Karen , Prasad Sharan , Ma Sung Jun , Iovoli Austin , Farrugia Mark , Malik Nadia Karen , Singh Anurag K. 
Published: June 2023

8538 Background: Due to concerns with toxicity, treatment of early-stage non-small cell lung cancer (NSCLC) with stereotactic body radiation therapy (SBRT) often involves different fractionation schemes for peripheral and centrally located tumors. There is a paucity of long-term SBRT survival outcomes comparing peripheral versus central NSCLC. Methods: This is a single-institution observational cohort study of patients diagnosed with early-stage NSCLC (T1-2N0M0) who underwent 27 Gy in 1 fraction or 50 Gy in 5 fractions with heterogeneity correction at Roswell Park Comprehensive Cancer Center between September 2008 to December 2018. All patients treated with single-fraction SBRT had peripheral NSCLC and those treated with five-fraction SBRT had central NSCLC. Clinically relevant variables including age, gender, race, Karnofsky Performance Status (KPS), histology (adenocarcinoma, squamous cell carcinoma, NSCLC not otherwise specified), T stage, smoking status, tumor location, and the year of SBRT delivery were obtained retrospectively. Cox multivariable analysis (MVA), Kaplan-Meier plot, and log-rank test were performed to evaluate progression-free survival (PFS) and overall survival (OS). Fine-Gray competing risk MVA was performed to evaluate local failure (LF), nodal failure (NF), and distant failure (DF) with death as a competing event. To reduce selection bias, propensity score matching was performed between single- versus five-fraction SBRT cohorts. Results: A total of 265 patients (142 female [53.6%]; median age 77 years) met our criteria. There were 74 (27.9%) and 191 (72.1%) patients with central tumors treated with five-fraction SBRT and peripheral tumors treated with single-fraction SBRT, respectively. On Cox MVA, there was no statistically significant difference in OS (peripheral vs central tumors: adjusted hazards ratio [aHR] 1.04, 95% confidence interval [CI] 0.74-1.46, p=0.81) and PFS (peripheral vs central tumors: aHR 1.05, 95% CI 0.76-1.45, p=0.77). On Fine-Gray competing risk MVA comparing peripheral vs. central tumors, there was no statistically significant difference in LF, NF, and DF. After propensity score matching, 68 matched pairs were identified for peripheral vs. central tumors with similar results. Conclusions: Among patients with early-stage NSCLC treated with SBRT central versus peripheral location was associated with similar long-term survival and tumor recurrence outcomes.
The RESECT study: Factors associated with overall survival (OS) and relapse-free survival (RFS) among patients with stages I–III resected NSCLC without known EGFR mutations.
Authors: Gray Jhanelle Elaine , Salomonsen Rachel , Georgoulia Nefeli , Diaz Perez Ignacio , Wang Alice , Cai Ling , Wetherill Graham , Xiao Yang , Fielden Claire , Altorki Nasser K. 
Published: June 2023

8541 Background: Approximately one-third of patients with Stages I–III resected non-small-cell lung cancer (NSCLC) do not survive 5 years from diagnosis. This retrospective observational study analyzed factors associated with OS and real-world (rw) RFS among Stage I–III NSCLC patients before the introduction of immuno-oncology (IO) treatment. Methods: We analyzed data from the US CancerLinQ database for adult patients with no known EGFR mutations and no other cancers, who were diagnosed with Stage I–III NSCLC from 2014–2019 and had surgical resection within 140 days after initial diagnosis. 3081 patients met the study criteria of whom 1677 were Stage I, 853 were Stage II, and 551 were Stage III; 4 Stage I patients who received neoadjuvant or perioperative treatment were excluded (too few for analysis). Most patients received surgery only (71.5%); the rest also received adjuvant (24.7%), neoadjuvant (2.4%) or perioperative (1.5%) treatment, most often chemotherapy ± radiotherapy. Key demographics, clinical characteristics, treatment patterns, and relevant 2-way interactions were considered for inclusion in the model, based on Cox regression analyses and medical insights. Multivariable Cox regression analysis (backwards selection, p<0.05) was used to model OS and rwRFS. Results: In the multivariable analyses (in which no Stage I patients with neoadjuvant or perioperative treatment were included), factors associated with both OS and rwRFS (p<0.05) were disease stage, race, ethnicity, year of diagnosis, ECOG performance status, and neoadjuvant treatment. Factors associated with OS (p<0.05), but not rwRFS, were age, sex, time from diagnosis to surgery, and type of surgery. Factors associated with rwRFS (p<0.05), but not OS, were geographic region, nodal status, and adjuvant treatment in Stage II and III patients but not Stage I patients. Conclusions: This study identified several risk factors associated with OS and rwRFS, many of which are known. Notably, in this analysis, neoadjuvant treatment was associated with both improved OS and rwRFS in Stage II–III patients and was not evaluable in Stage I patients. However, adjuvant treatment was only associated with improved rwRFS, and only in Stage II–III patients. Based on these findings, there remains an unmet need for Stage I–III NSCLC patients. The recent introduction of IO treatment in this setting may help improve patient outcomes.
Two-year lung cancer survival between 2000 to 2020: Results from 3 French nationwide cohorts.
Authors: Debieuvre Didier , Monnet Isabelle , Bylicki Olivier , Schneider Sophie , Goupil Francois , Godbert Benoit , Dussopt Christine , Pegliasco Herve , Portel Laurent , Chikouche Reda , Masson Philippe , Jaafar Mohamad , Marty Clothilde , EL Khanjari Fethi , Obert Julie , Picaud Marjorie , Bravard Anne Sophie , Le Floch Herve , Letierce Alexia , Morel Hugues 
Published: June 2023

8542 Background: Each decade since 2000, the French College of General Hospital Pulmonologists (CPHG) conducts the KBP study, a real-life nationwide prospective multicenter study on LC in non-academic public hospital (NPH). Here, we report the two-year survival (2-y) rate among the 2020 cohort and the comparisons with the 2000 and 2010 cohorts. Methods: Collection of all consecutive diagnosed LC, all stage and all histology, between 01/01 and 12/31 in NPH pulmonology or oncology units in 2000, 2010 and 2020 with the same methodology. A Scientific Committee controlled inclusion exhaustivity and quality in each center. Survival rates were calculated using the Kaplan-Meier method and risk factors were assessed using Cox models. Results: 8,999 patients were included in 82 centers in 2020. The 2-y survival rate was 40.3%, the median overall survival was 15.3 months. Compared to 2000, mortality rates at 2 years decreased significantly (-19.1%), while early (1 month and 3 months) mortality remains similar. Survival improved in 20 years whatever histologic types (Table). Factors associated with 2-y survival were sex (36.1% vs 48.1% respectively for male and female respectively, significantly increased over 20 years: + 15.3% for M and + 24.5% for F), high age (>80 y-o), poor ECOG status (3 or 4) and advanced disease. As expected in 2020, TNM stage was still determining for 2-year mortality, 15.2 [12.6-17.7] stage I vs 75.6 [74.4-76.8] stage IV. In 2020 the Covid-19 infection (n=283) impacted the survival (HR = 4.02 95%CI [3.33-4.86]) on multivariate analysis adjusted to age, sex, tobacco consumption, histology, ECOG status, TNM stage. Conclusions: These results confirmed the major improvement in the last two decades for LC. 5-years survival will provide us more enlightenment. [Table: see text]