bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of lymph node metastasis using 5-point visual scale criteria of [18F]-fluoro-2-deoxy-D-glucose on positron emission tomography / computed tomography for early stage lung adenocarcinoma.
Authors: Kagimoto Atsushi , Tsutani Yasuhiro , Handa Yoshinori , Mimae Takahiro , Miyata Yoshihiro , Okada Morihito 
Published: May 2020

e21084 Background: This study aimed to investigate the efficacy of the Deauville criteria, a 5-point visual scale criteria to assess the maximum standardized uptake value (SUVmax) of [18F]-fluoro-2-deoxy-D-glucose (FDG) on positron emission tomography (PET)/computed tomography (CT), in predicting lymph node metastasis and other pathological invasive characteristics of early-stage lung adenocarcinoma. Methods: In this retrospective study including 453 patients undergoing lobectomy or segmentectomy with lymph node dissection for clinical N0 lung adenocarcinoma with a whole size ≤ 3 cm between April 2011 and March 2019, the FDG-PET/CT scans were evaluated using the Deauville criteria to analyze the relationship of Deauville score with the clinicopathological characteristics and prognosis.The scoring method was as follows: Deauville score of 1, no FDG uptake by the primary tumor (same as background); Deauville score of 2, tumor FDG uptake that is the same as or weaker than that of mediastinum; Deauville score of 3, tumor FDG uptake that is stronger than that of mediastinum but same as or weaker than that of liver; Deauville score of 4, tumor FDG uptake that is moderately higher than that of liver; Deauville score of 5, tumor FDG uptake that is markedly stronger than that of liver. Results: The lymph node metastases were present in 0 (0%), 2 (1.1%), 6 (9.5%), 6 (15.8%), and 13 (15.7%) patients with Deauville scores of 1, 2, 3, 4 and 5, respectively. The pathological invasive characteristics (lymphatic, vascular, or visceral pleural invasion) were detected in 2 (2.4%), 17 (9.9%), 18 (28.6%), 23 (60.5%), and 54 (65.1%) patients, respectively. Similar results were found when the study cohort was analyzed according to the institutions where the FDG-PET/CT scans were performed. The 3-year recurrence-free survival was longer in the patients with a Deauville score of 1–2 (97.2%) than those with a Deauville score of 3 (86.2%, p < 0.001) or 4–5 (80.7%, p < 0.001). Conclusions: The 5-point-scale evaluation of the SUVmax on FDG-PET/CT using the Deauville score was useful in predicting not only lymph node metastasis but also other malignancy characteristics of early-stage lung adenocarcinoma.
Propensity score matching analysis of patients with inoperable stage III NSCLC treated with chemoradio- vs. chemoradioimmunotherapy.
Authors: Manapov Farkhad , Taugner Julian , Käsmann Lukas , Eze Chukwuka , Roengvoraphoj Olarn , Belka Claus 
Published: May 2020

e21087 Background: Chemoradiotherapy (CRT) followed by consolidation treatment with the PD-L1 Inhibitor durvalumab is the new standard of care for inoperable stage III NSCLC. The present study compares outcome of patients treated with CRT alone to those treated with additional concurrent and/or sequential immune check-point inhibition (CRT-IO) using propensity-score matching analysis (PSM). Methods: PSM was performed with retro- and prospectively collected data of patients treated with CRT or CRT-IO (consolidation with durvalumab/concurrent and consolidation with nivolumab). Overall survival (OS), progression free survival (PFS) and time to loco-regional recurrence (defined as progression in the mediastinum and ipsilateral lung) were calculated from last day of thoracic irradiation. Results: Sixty-two (37%) of 166 treated patients were successfully matched; 31 received CRT and 31 CRT-IO. 18F-FDG-PET/CT for treatment planning was performed in 97% and cranial contrast enhanced MRI in 81% of patients. PSM was based on age, gender, PTV volume, histology, T- and N-stage. 36 and 51% vs. 42 and 46% of patients had T4- and N3-disease in the CRT and CRT-IO cohorts, respectively. All patients were irradiated to a total dose of at least 60Gy (EQD2). 90% of patients received two cycles of concomitant platinum-based chemotherapy (CRT: 82%, CRT-IO 96%). The median follow-up for 62 patients was 17.3 (range: 1.7-96.0) months. Median PFS was 7.1 (95%CI 2.2-12.1) months in CRT vs. 13.8 (95%CI 13.1-14.5) in CRT-IO patients (p = 0.004). Twelve-month PFS rates were 30% and 55% in the CRT and the CRT-ICI cohort, respectively. Median time to loco-regional recurrence was 15.3 months for CRT vs. not reached for CRT-IO patients (p = 0.050). 12-month loco-regional recurrence rates were 43% vs. 22%; 6- and 12-month brain metastases rates after completion of radiotherapy in the CRT vs. CRT-ICI cohort were 8% and 26% vs. 0% and 20%, respectively. Median OS was 19.1 (8.4-29.8 95%CI) months for CRT and not reached for CRT-IO patients (p < 0.001). 12-month survival rates were 62% and 93% in the CRT and CRT-IO cohort, respectively. Conclusions: The addition of concurrent and/or sequential IO to CRT led to an impressive improvement of loco-regional control, PFS and OS in the matching cohorts.
Intratumoral heterogeneity and tumor evolution of small cell lung cancer through multi-regional sequencing.
Authors: Zhang Yaxiong , Zhou Ningning , Zhou Huaqiang , Song Mengmeng , Li Pansong , Guan Yan-Fang , Xia Xuefeng 
Published: May 2020

e21103 Background: Small cell lung cancer (SCLC) is a type of aggressive malignancy with poor prognosis, accounting for 15% of lung cancers. Intratumoral heterogeneity (ITH) has been investigated in lung adenocarcinoma or squamous cell carcinoma, but its role in SCLC still remains unclear. Exploring ITH and tumor evolution of SCLC is essential for its treatment and prognosis. Methods: 102 multi-regional tumor tissues were collected from 34 operative SCLC patients (pts) before systemic therapy during Sep. 2009 to Sep.2018 from Sun Yat-sen University Cancer Center. All of the enrolled cases were confirmed as SCLC by immunohistochemistry. We performed whole-exome sequencing (WES) of all the tumor tissues and assessed the ITH using clonal and subclonal somatic mutations or copy number variants. ITH was defined as the proportion of subclonal genetic alterations of all. The relationship between ITH and overall survival (OS) was also explored. Results: Among the enrolled 34 SCLC pts, the median age was 64 year. 28 pts had the smoking history. 23 pts received adjuvant therapy after surgery. Stage I-II and III-IV pts accounted for 50% respectively. The most frequent mutated genes were TP53 (88%), RB1 (70%), TTN (68%), TCEB3CL (65%), MUC16 (56%), and all of them were clonal. The median overall ITH was 0.36 (ranging from 0 to 1), while the mutational ITH and the CNV ITH were 0.50 (0.22 to 1) and 0.49 (0.22 to 1). Univariate analysis revealed that postoperative treatment (HR = 0.27, 0.07-0.97, p= 0.006) and higher CNV ITH (HR = 0.28, 0.08-0.99, p= 0.009) were significant positive predictors of OS, while higher mutational heterogeneity was not associated with OS (HR = 3.34, 0.91-12.25, p= 0.21) significantly. Conclusions: TP53, RB1, TTN, TCEB3CL and MUC16 were probably clonal mutations as early events in SCLC evolution. CNV ITH might be a prognostic predictor in SCLC, which should be verified in a large-sample cohort.
Is there a role for hypofractionated thoracic radiotherapy in limited-stage small cell lung cancer? a propensity score matched analysis.
Authors: Zayed Sondos , Chen Hanbo , Ali Emma M , Rodrigues George , Warner Andrew , Palma David A. , Louie Alexander V 
Published: May 2020

e21107 Background: Concurrent chemoradiotherapy is the standard of care for limited-stage small cell lung cancer (LS-SCLC). While conventional fractionation (CF) and hyperfractionation are the most commonly used radiotherapy schedules worldwide, hypofractionation (HF) continues to be a standard radiation regimen used in several countries. In the absence of randomized evidence comparing CF and HF, the aim of this study was to compare overall survival (OS), progression-free survival (PFS), and toxicity outcomes for CF and HF in LS-SCLC. Methods: In this single institution retrospective review, consecutive LS-SCLC patients treated between 2000-2013 with HF (40Gy/15, 45Gy/15, 45Gy/20 fractions) or CF (60Gy/30 or 66Gy/33 fractions) were included. Propensity scores were generated using a multivariable logistic regression model. Patients were matched on a 1:1 ratio with a caliper distance of 0.20. OS and PFS were estimated using the Kaplan-Meier method with differences evaluated using log-rank tests. As a sensitivity analysis, univariable and multivariable Cox regression was performed in all unmatched patients. Logistic regression was performed to identify predictors of all pulmonary and esophageal adverse events. Results: In the 117 patients, there were significant baseline differences between the CF and HF cohorts. Patients who received CF were older, smoked more often concurrently with treatment, had higher ECOG performance status, different T and N stage patterns, and more commonly received concurrent chemoradiotherapy and prophylactic cranial irradiation. After propensity score matching, 72 patients were included, 36 in the HF and CF cohorts respectively. No statistically significant difference was noted between matched HF and CF cohorts for OS (P = 0.724) or PFS (P = 0.862). Similarly, multivariable Cox regression revealed no differences in OS (P = 0.886) or PFS (P = 0.717) between HF and CF in all unmatched patients. There was no difference in any pulmonary (P = 0.350) or esophageal (P = 0.097) adverse events between matched HF and CF cohorts. Skin adverse events were significantly higher for CF (41.7%) compared with HF (16.7%, P = 0.020) in matched patients. No grade 5 adverse events were observed. Conclusions: In this propensity score matched comparison of HF and CF in LS-SCLC patients who underwent curative-intent radiation treatment, HF and CF were associated with comparable OS, PFS, and toxicity outcomes. HF may therefore be a reasonable alternative to CF, should its efficacy be confirmed in prospective studies.
Real-world data on liquid biopsies utilization in lung cancer patients in the community setting: The Mount Sinai experience.
Authors: Dvir Kathrin , Galarza Fortuna Gliceida , Haines Joel M. , Drusbosky Leylah , Febres-Aldana Christopher , Gines Paulina , Rodriguez Estelamari 
Published: May 2020

e21502 Background: Liquid biopsy describes the extraction of circulating tumor DNA (ctDNA) from peripheral blood via next-generation-sequencing (NGS). The yield of adding plasma-based NGS to tissue NGS for the detection of Actionable Mutations (AM) have been reported scarcely and additional “real world” data is needed. Methods: In this retrospective data review, we included patients with non-small cell lung cancer (NSCLC) who had plasma NGS genomic testing ordered between Nov 2014 and July 2019, as part of routine management. Plasma testing was performed using Guardant360 commercial platform and was analyzed for therapeutically AM in: EGFR, ALK, MET, BRCA1, BRCA2, KRAS, ROS1, RET, ERBB2, BRAF, and NTRK2. Results: Over a period of 5 years, 337 samples taken from 279 patients were sent for ctDNA NGS testing. The median age at diagnosis was 73 years [range 36-93, SD:10.4], 51% (N=141) were males and 49% (N=138) were females. Excluding synonymous mutations and variants of unknown significance, 239 samples (71%) and 201 patients (72%) had 705 somatic mutations. Of them, 36% (N=254) were therapeutically actionable and were detected in 139 samples (58%), taken from 106 patients (53%). Commonly detected AM were EGFR (N=127; 50%), KRAS (N=61; 24%), BRAF (N=24; 9.5%), MET (N=23; 9%), RET (N=5; 1.9%), BRCA1 (N=5; 1.9%), BRCA2 (N=4; 1.6%), ERBB2 (N=4; 1.6%) and ALK (N=1, 0.4%). None of the samples had mutations in ROS1, NTRK2. One patient had Microsatellite instability (MSI). Common co-occurring mutations were EGFR and BRAF (N=14), EGFR and MET (N=13) and MET and BRAF (N=10) (p<0.001). Common mutually exclusive mutations were KRAS and EGFR (p<0.001). Tissue NGS analysis was performed in 62/106 patients (58%), with AM found in 45 patients (72%). Concordance agreement in AM between plasma and tissue NGS modalities was detected in 39/45 patients (87%) and was demonstrated in EGFR (N=25), KRAS (N=11), BRAF (N=2) and MET (N=1). In the reminder 6 patients (13%), tissue NGS was discordant from their plasma NGS results. In 44/106 patients, for whom tissue sampling was not performed, utilizing plasma NGS increased AM detection yield by 41%. Conclusions: Integration of plasma NGS testing into the routine management of NSCLC patients demonstrated substantial yield of therapeutically targetable mutations detection rate, when tissue NGS was not available.
Neoantigen screening identifies EGFR L858R mutation immunogenicity in 1862 Chinese NSCLC patients.
Authors: Lin Jin , Chen Yu , Chen Gang , Jun Liu , Hao Shiguang , Xiong Jia-ni , Lan Bin , Xu Yaping , Guan Yan-Fang , Guo Zengqing , Chen Lin , Chen Li-zhu , Xia Xuefeng 
Published: May 2020

e21512 Background: Therapeutic vaccines targeting mutation-derived neoantigens prime T-cell responses and deliver long-term clinical benefit to patients. Last year we reported EGFR L858R mutation could be a possible target for individual-independent vaccine in 799 Chinese patients with non-small cell lung cancer (NSCLC). Here we verified the findings and explored possible immunological mechanisms in a larger sample size of 1862 Chinese NSCLC. Peripheral blood or normal tissue was used as control. Methods: DNA sequencing data was acquired using our targeted 1021-gene panel and HLA-I genotyping was determined based on DNA sequencing by OptiType v1.0. The peptide-HLA binding affinity was predicted with netMHCpan v4.0. Neoantigen was identified if the IC50 MT < 500 nM and IC50 WT > 500 nM, furthermore, IC50 MT < 50 nM was considered as strong-binders. Results: EGFR (50.05%) was the most prevalent mutated gene, with 22.61% and 13.16% harboring L858R mutations and E746_A750del respectively. HLA typing showed HLA-A*11:01(42.59%) was the top one allele and HLA-A*33:03(12.94%) ranked 12th. The combination of EGFR L858R and HLA-A*33:03 had both relatively strongest binding affinity (IC50 MT = 22.9 nM and IC50 WT = 12734.0 nM, 2.93%) and highest shared frequency (2.93%). In terms of mechanism, we examined 7 of 1862 (0.37%) B2M gene mutation and 1092 of 1731 (63.1%) HLA-I LOH (loss of heterozygosity) in our population, but didn’t see any statistical difference between L858R subtype and other position mutations in EGFR. We also calculated 26 immune cell types’ signature scores from Chinese CHOICE study and found L858R subtype was associated with elevated level of pDC (KW-test p = 0.02) and lower level of neutrophils signature(KW-test p = 0.07) compared with exon 19 deletion and other uncommon mutations of EGFR. Conclusions: (1) Targeting EGFR L858R mutation in patients with HLA-A*33:03 allele appeared to be valuable for the neoantigen-based vaccine designed for Chinese NSCLC patients. (2) The specific immunogenicity of L858R seemed to be little influenced by B2M mutation and HLA-I LOH which were important factors for neoantigen presentation. (3) High pDC and low neutrophils infiltration might contribute to the inhibitive microenvironment associated with L858R mutation.
Using real-world data to investigate time-dependent blood count response to PD-1 and PD-L1 inhibitors and its impact on survival in advanced non-small cell lung cancers.
Authors: Ayers Kristin , Liu Zongzhi , Ma Meng , Lee Kyeryoung , Newman Scott , Li Li , Zhou Xiang , Mullaney Tommy , Redfern Arielle , Jappe Whitney , Zimmerman Michelle , Prentice Tony , Oh William , Schadt Eric , Li Dan , Chen Rong 
Published: May 2020

e21514 Background: Although some advanced non-small cell lung cancer (aNSCLC) patients respond favorably to immune checkpoint inhibitors, a larger portion either do not respond or experience negative side effects. At present, there is no consensus on how to best predict response to immunotherapy (IO) agents. Complete blood count (CBC) data have shown correlation with both progression and survival for patients treated with IO. However, previous studies have been relatively small, or did not focus on aNSCLC. Given CBCs are measured routinely for every patient throughout their course of therapy, we used real-world data (RWD) to assess the biomarker potential of CBCs in predicting response at the start and through the course of therapy. Methods: We performed a retrospective cohort study of 11,138 lung cancer patients treated at hospitals in the Mount Sinai Health System of whom 249 aNSCLC and were treated with anti-PD1/PD-L1 therapy. We extracted and harmonized medical record data using an automated abstraction engine and evaluated the impact of changes in CBCs, including eosinophils, lymphocytes, monocytes, neutrophils, red blood cells and platelets after treatment initiation. Time to treatment discontinuation (TTD) and overall survival (OS) were our clinical endpoints. Results: Abnormal baseline levels of monocytes, neutrophils, and red bloods cells were associated with OS; counts taken between 2-8 weeks were modestly to significantly associated with poorer OS, with hazard ratios ranging from 1.7-4.7. Most strikingly, neutrophil levels above 7 (HR = 4.3, p = 3.2*10−10, 95% CI = 2.7-6.7) and a neutrophil-to-lymphocyte ratio > 5 (HR = 3.4, p = 8.0*10−8, 95% CI = 2.2-5.4) were associated with poorer OS. For those with normal neutrophil levels at baseline, progressing to high levels at 2-8 weeks resulted in a hazard for OS of 5.0 (p = 4.4*10−8, 95% CI = 2.8-9.0). Those with progression are more likely to have high neutrophil levels at baseline, or an increase in neutrophil levels from normal to high levels between baseline and 2-8 weeks or 8-14 weeks. Our results remained consistent even after controlling for factors that may affect neutrophil levels including concurrent chemotherapy, administration of neutropenia medications, or concurrent infections. Repeating the analysis with TTD as the primary endpoint showed similar but less significant trends. Conclusions: RWD showed changes in blood cell counts after anti-PD1/PD-L1 therapy were associated with OS in aNSCLC and show promise as a predictive biomarker.
Clinical and molecular characteristics of the patients in the liquid biopsy study in mEGFR-NSCLC in a Spanish population (OPH-1).
Authors: Franco Fernando , Serna Roberto , Sanchez Alfredo , García Girón Carlos , Domine Manuel , Camps Carlos , Sanchez Torres Jose Miguel , Oramas Rodriguez Juana Maria , Chara Velarde Luis Enrique , Ortega Ana Laura , Sala Maria Angeles , Hernandez Berta , Sereno Maria , Bosch-Barrera Joaquim , Padilla Airam , Balsalobre Yago Jose , Blanco Remei , Mielgo Xabier , Romero Atocha , Provencio-Pulla Mariano 
Published: May 2020

e21515 Background: The liquid biopsy (LB) is an important tool in the diagnostic and follow up of the patients with non-small cell lung cancer (NSCLC) and can provide big information about the mutational variability of the disease during of the treatment. Methods: We conducted a multicenter study with 200 patients with EGFR-mutated NSCLC, treated with first-line TKI therapy. We analyse the ctDNA by dPCR pre-treatment, at 8 weeks, at 7 months and at the progression of the disease (PD). Results: A total of 200 patients (60% women / 40% men) were included. The median of age was 68-year. The never smokers were 56% and 34% ex-smokers. 92% of the cases were adenocarcinomas. According to the stage of the disease, 52% were stage IVB, 38.5% stage IVA and 9.5% unknown. The first-line treatment was afatinib in 47.5%, erlotinib in 21.5% and gefitinib in 31%. According to the type of sensitivity mutation, 61.5% corresponded to Del19, 32% to L858R, 2.5% to G719X and 2.5% to L861Q. At the time of diagnosis, 63% had pulmonary metastatic involvement and 42.5% liver metastasis. At the time of data analysis, 66% of the patients had some progression of the disease (PD) and 37% died. 68% of the patients with Del19 received afatinib, while 20% of the patients with L858R received afatinib, 54.5% erlotinib and 32% gefitinib (p = 0.02). With a median follow-up of 20 months, progression-free survival was 11.8 months, without any differences according to the treatment (p = 0.93). The groups with worse PFS included: the squamous histology (HR 5.7; 95%CI 2.04-15.91, p = 0.001), the G719X mutation (HR 3.36; 95%CI 1.21-9.25, p = 0.019) and the liver metastasis (HR 1.65; 95%CI 1.01-2.68, p = 0.042). The sensitizing mutation was detected in the 80.8% of the patients in the LB by dPCR and the T790M in 2%. However, in the first control only was detectable in 18.5%. At the time of PD, the percentage of detection of T790M raised to 52.3%, and the sensitizing mutation 79.44%. At that moment, patients who developed T790M were mostly never smokers (66%, p = 0.006) and had Del19 (66%). Patients with bone progression developed T790M in 60.4% (p = 0.014) and hepatic 27% (p = 0.012). Conclusions: We concluded that the clinical characteristics of the patients of the OPH study are consistent with the previous reported in the Caucasian population and the subgroups with the worst prognosis include the squamous histology, the G719X mutation and the liver metastasis.
Association of HLA class 1 homozygosity with unfavorable clinical outcomes in patients with non-small cell lung cancer (NSCLC) treated with PD-1 inhibitor as first-line therapy.
Authors: Chae Young Kwang , Lee Dongyup , Park Jonghanne , Choi Horyun , Gim Gahyun , Cho Sukjoo , Kim Leeseul , Oh Youjin , Kang Cyra Y , Viveiros Pedro Antonio Hermida de 
Published: May 2020

e21519 Background: Homozygosity at human leukocyte antigen class I (HLA-I) locus has been reported to be an unfavorable predictive biomarker of second line or beyond immunotherapy in patients with different types of cancer including melanoma and NSCLC. The linkage between HLA-I homozygosity and survival outcomes in NSCLC patients treated with first-line immunotherapy has not been reported. Methods: Next generation sequencing with HLA genotyping was performed for patients with unresectable stage III or IV NSCLC treated with pembrolizumab plus chemotherapy as first line (N = 25). Progression free survival (PFS) was compared between HLA-I homozygous (defined as homozygosity in at least one locus A, B, or C) and heterozygous patients. Kaplan-Meier curves were built and Log-rank test was used to compare unadjusted survival statistics between the groups. Cox Proportional Hazards were then used to adjust for potential confounders; age, sex, and tumor mutation burden status (TMB, above vs. below median). Results: The median follow up time was 259 days [interquartile range,163 to 350]. Among 25 enrollees, 21 patients (84%) were HLA-I heterozygous and 4 patients (16%) were HLA-I homozygous. Treatment response was not available in 6 patients with HLA-I homozygosity. Among 15 patients with HLA-I homozygosity, 4 patients (26.7%) had partial response (PR), 7 patients (46.7%) had stable disease(SD), and 4 patients (26.7%) had progressive disease (PD). Among 4 patients with HLA-I heterozygosity, 1 patient (25%) had PR, 1 patient (25%) had SD, and 2 patients (50%) had PD. The disease control rates (PR and SD) were 73.4% in heterozygous group and 50% in homozygous group. The heterozygous group showed longer median PFS than the homozygous group (19 vs. 9.4 months, Log-rank p = 0.14). Patients with HLA-I homozygosity demonstrated shorter PFS (HR = 2.35, 95% CI = 0.56-9.9, p = 0.25). Adjusted HRs controlled for age, sex, and TMB were 3.6[0.65-20], 2.3[0.55-9.9] and 1.7[0.34-8.6] respectively. Conclusions: We observed a trend toward an inverse association between HLA-I homozygosity and survival outcomes in patients with NSCLC treated with first-line immunotherapy. Further perspective studies to validate such relationship are warranted.