bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of patients with unresectable stage III non-small cell lung cancer treated with durvalumab and subsequent therapies after disease progression.
Authors: Dickson Franco Adjei-Baffour , Raez Luis E. , Dumais Katerine , Powery Herman W. , Walker Damaal 
Published: June 2021

e20531 Background: The PACIFIC trial demonstrated that durvalumab improved 3-year overall survival in unresectable Stage III non-small-cell lung cancer (NSCLC) following chemoradiotherapy (CRT). However, there is no consensus on the preferred therapy after patients progress on durvalumab. This study aimed to determine the real-world outcomes of patients treated with durvalumab and subsequent therapies after disease progression. Methods: Forty-five NSCLC patients previously treated in a large multi-site community cancer center with concurrent CRT followed by durvalumab were evaluated for progression-free survival (PFS). Subsequent lines of therapy for patients who progressed on durvalumab were also evaluated. Treatment characteristics of the patients were also reviewed. PFS was reported using the Kaplan-Meier method using a p-value of < 0.05 for statistical significance. Results: Baseline characteristics of patients included a median age of 65 years (46-90), 99% with ECOG 0 or 1, and 89% with PDL-1>50%. The median duration between the end of CRT and initiation of durvalumab was 1.3 months and the median treatment duration was 8.1 months the A total of 13 patients (29%) progressed on durvalumab; the 12-month PFS was 65.9% (49-79.7) and the 18-month PFS was 59.1% (36.7-76.1). The median PFS observed was 38.4 months (Table 1). The subsequent lines of therapy for the 14 patients that progressed were as follows: 8(62%). immunotherapy/chemotherapy combination, 2(15%) chemotherapy only, 2(15%) targeted therapy, and 1(8%) radiation therapy. Conclusions: Evaluation of consolidation durvalumab in patients with locally advanced NSCLC finds PFS in clinical practice to be consistent with trial data. Subsequent lines of therapy were consistent with guideline recommendations for newly diagnosed stage IV NSCLC. Longer follow-up will be needed to determine the PFS associated with the different subsequent therapies and how immunotherapy failure could potentially affect outcomes of subsequent chemo/immunotherapy combinations.[Table: see text]
Non-small cell lung cancer population mortality and stage shift.
Authors: Patel Parth Bhargav , Alpert Naomi , Pyenson Bruce , Taioli Emanuela , Flores Raja Michael 
Published: June 2021

e20536 Background: Lung cancer population mortality has decreased over the last decade. Smoking cessation, medical therapies, CT screening, and earlier therapeutic interventions may all contribute to this decrease. We investigate the role of stage shift on population mortality of non-small cell lung cancer (NSCLC). Methods: Data from Surveillance, Epidemiology, and End Results (SEER) were queried to assess all patients from 2006-2016 with microscopically confirmed NSCLC. Incidence based mortality was evaluated by year of diagnosis. In order to assess shifts in diagnostic characteristics, stage and histology distributions were examined by year using χ2 tests. Trends were assessed by using the average annual percentage change (AAPC), calculated with JoinPoint software. Kaplan-Meier survival analysis was also performed to assess overall survival according to stage and to compare those missing any stage to those with a reported stage. Results: Between 2006-2016, 312,382 patients in SEER were diagnosed with NSCLC. Incidence based mortality within 5 years of diagnosis for NSCLC has significantly decreased over the last decade (AAPC -3.7 (95% confidence interval (CI): -4.1 - -3.4)). When assessing stage shift, there was a significant association between year of diagnosis and stage (p < 0.0001), with the percent in each year diagnosed at stage I/II increasing from 26.5% to 31.2% from 2006-2016, corresponding to a statistically significant AAPC of 1.5 (95% CI: 0.5-2.5); the percent diagnosed at stage III/IV decreased significantly from 70.8% to 66.1% (AAPC: -0.6 (95% CI: -1.0 - -0.2)). The percent missing staging information was relatively stable in this timeframe and not significant (AAPC: -1.6 (-7.4 - 4.5)). Year of diagnosis was significantly associated with tumor histology (p < 0.0001). There was a statistically significant increase in the percent of those diagnosed with adenocarcinomas, from 42.9% in 2006 to 59.0% in 2016 (AAPC: 3.4 (95% CI: 2.9-3.9)). Median survival for those with stage I/II was 57 (interquartile range (IQR): 18- - ) months; for stage III/IV was 7 (IQR: 2-19) months; and for those missing stage was 10 (IQR: 2-28) months. Patients with stage I/II had significantly better survival compared to those diagnosed with stage III/IV, or missing stage (p < 0.0001). Conclusions: Population-level mortality for NSCLC has decreased from 2006-2016. While advances in treatments, particularly targeted therapeutics have played a role in affecting mortality, our analysis suggests that decreased mortality is also due to a diagnostic shift from later to earlier stage lung cancer. Studies investigating the effectiveness of treatment on lung cancer mortality must take into account the confounding effect of stage shift on survival and mortality outcome.
Immune-related histologic phenotype in pretreatment tumor biopsy predicts pathologic response to neoadjuvant anti-PD-1 treatment in squamous lung cancer.
Authors: Yuan Pei , Guo Changyuan , Li Lin , Ling Yun , Guo Lei , Li Junling , Ying Jianming 
Published: June 2021

e20540 Background: The neoadjuvant platform affords a rich and valuable resource for understanding the responses to therapy and carrying out reverse translation, including pathologic morphology. We aimed to develop a pretreatment histologic scoring system reflecting the preexisting immune response to predict the efficacy of neoadjuvant immunotherapy based on the morphological changes we mastered in the pathologic assessment after neoadjuvant immunotherapy. Methods: Surgical specimens from the 31 squamous cell lung cancer patients recruited in a phase Ib study of neoadjuvant anti-PD-1 therapy and eligible paired pretreatment biopsies from 15 of them were included in this study. The posttreatment surgical specimens were assessed according to the immune-related pathologic response criteria. Immune-related histologic phenotype assessment criteria (irHPC) were developed based on the pathologic features identified after neoadjuvant anti-PD-1 treatment. Three pathologists trained for irHPC independently scored the HE slides of the 15 pretreatment tumor biopsies according to irHPC. Results: Whether necrosis was included in the calculation of percent of residual viable tumor (%RVT) or not had almost no effect on the consistency of pathologic assessment ( P= 0.811) and the histological response grouping. The inter-pathologist variability of assessing %RVT with immune-activated phenotype was not statistically significant ( P= 0.480). Four immune-related features of pretreatment biopsies were included for calculating the predictive score, including three positive features (tumor-infiltrating lymphocytes, tumor-infiltrating eosinophils and dense plasma cells in stroma) and one negative feature (tumor-infiltrating neutrophils) according to the developed irHPC scoring system. The trained pathologist accurately predicted 6 out of 8 patients in the cPR/MPR group and 5 out of 7 patients in the non-cPR/MPR group according to irHPC. For inter-observer reproducibility using “2 points” as the cut-off point, the overall percent agreement (OPA) was 77.8%. The reliability between pathologists for a binary tumor evaluation showed “moderate” agreement (κ = 0.54). Conclusions: The irHPC scoring system reflecting the preexisting immune response could be used to predict the pathologic response of neoadjuvant immunotherapy, but still needs the larger trails to verify.
SMARCA4-mutated lung adenocarcinoma, a distinctive non-small cell lung cancer with worse prognosis.
Authors: Zhang Longfeng , Xiao Weijin , Wu Fangjun , Peng Ran , Shi Jialong , Li Chao , Lin Gen 
Published: June 2021

e20548 Background: SMARCA4 gene is one of the catalytic subunits of the SWI/SNF chromosomal remodeling complex, which can regulate important cellular processes and functions and is closely associated to tumors. The clinical features, therapeutic efficacy, prognosis and pathological features of lung adenocarcinoma with this genetic variation are still unknown and controversial. Methods: The study recruited 274 patients (pts) with lung adenocarcinoma whose samples were sent to perform parallel hybridization-based next-generation sequencing. Two categories of SMARCA4 mutations were divided into Type1 mutations (frameshift mutations, nonsense mutations, splice-3 mutations, copy number amplification) and Type2 mutations (missense mutations and copy number loss) based on whether the mutation may result in defective protein. Furthermore, comparative analysis by using the clinical outcome data, the genomic and pathological characteristics were be performed in SMARCA4 Type 1 alterations corhort and Type 2 alterations corhort. Results: Among 274 pts were recruited, the mutation rate of SMARCA4 gene in lung adenocarcinoma was 9.1%. Furthermore, the presence of SMARCA4 alteration was associated with smoking (P＜0.05). Missense, nonsense, frameshift and splice were the most common types of mutations (92%). The pts with SMARCA4 Type1 alterations which probably lead to defective protein expression, had a worse prognosis compared with pts with SMARCA4 Type1 alterations (The role leading to defective protein expression is uncertain) and SMARCA4 Wild groups (P＜0.05). In addition, EGFR alterations were strongly associated with SMARCA4 Wild corhort compared to SMARCA4 Type1 alterations corhort (67% vs. 31% ), and SMARCA4 Type1 alterations was more associated with the absence of TP53, RB1, and Robo3 alterations. GO enrichment analysis suggested that the differentiated mutated genes between SMARCA4 Type1 alterations corhort and SMARCA4 Wild corhort were mainly enriched in cell cycle regulation. Pathologically, The SMARCA4 Type1 alterations was mostly poorly or moderately differentiated and strongly accompanied by the loss of expression of TTF-1(83.3%) and BRG1(80%) in immunohistochemistry. Conclusions: SMARCA4 Type1 alterations which probably lead to abnormality of protein was associated with poor prognosis and having different the genomic and pathological characteristics.
Adoption of consolidative durvalumab among patients with locally advanced non-small cell lung cancer.
Authors: Jairam Vikram , Pasha Saamir , Soulos Pamela R. , Goldberg Sarah B. , Yu James B. , Decker Roy H. , Gross Cary Philip , Park Henry S. 
Published: June 2021

e20550 Background: Soon after the publication of the PACIFIC trial, the Food and Drug Administration (FDA) approved durvalumab following definitive chemoradiation in patients with unresectable stage III non-small cell lung cancer (NSCLC). However, patterns of durvalumab adoption within the United States are currently unknown. We investigated the pace of uptake of durvalumab as well as patient and tumor characteristics associated with receipt of durvalumab following FDA approval. Methods: This study used the nationwide Flatiron Health database, a longitudinal electronic health record-derived de-identified database. During the study period, the de-identified data originated from approximately 280 US cancer clinics (̃800 sites of care). From this de-identified database, we selected patients with stage IIIB-C NSCLC who completed at least two cycles of first-line (1L) platinum doublet chemotherapy between February 16, 2018 (FDA approval date for durvalumab) and August 16, 2019, and did not develop disease progression over a follow-up period of at least 120 days after 1L chemotherapy. In the absence of radiation therapy and surgery details in the database, these criteria served as a proxy for selecting patients who were most likely to be eligible for consolidative durvalumab. We evaluated temporal trends in the uptake of durvalumab after completion of 1L chemotherapy using the Cochran-Armitage test, clustering the time periods in 3-month intervals. We also characterized patient and tumor characteristics associated with durvalumab receipt using the chi-square test and multivariable logistic regression. Results: A total of 424 patients were included in our study sample, among whom 282 (66.5%) patients had documentation of having received durvalumab after 1L chemotherapy. Within the first 3 months after FDA approval, 60.4% of potentially eligible patients received durvalumab, while in the final 3 months of the study period, this proportion rose modestly to 68.3% (p = 0.19). On univariable and multivariable analysis, patient characteristics like age, sex, race, insurance, smoking status, performance status, and comorbidity score, as well as tumor characteristics like histology, EGFR status, and PD-L1 status, were not significantly associated with receipt of durvalumab. However, there was significant geographic variability in receipt of durvalumab, ranging from 65.7% in the South to 85.3% in the Midwest (chi-square p = 0.04). Conclusions: Early adoption of durvalumab upon completion of 1L chemotherapy for stage IIIB-C lung cancer was rapid across the United States, starting at over 60% in the first three months after FDA approval. Regional variation appears to be a more powerful driver than patient characteristics in discrepancies of durvalumab dissemination. Further exploration into these regional variations may help improve guideline-concordant care.
Association of planning target volume with disease progression in inoperable stage III non-small cell lung cancer patients treated with chemoradiotherapy and concurrent and/or sequential immune checkpoint inhibition.
Authors: Taugner Julian , Karin Monika , Käsmann Lukas , Eze Chukwuka , Guggenberger Julian , Flörsch Benedikt , Tufman Amanda , Belka Claus , Manapov Farkhad 
Published: June 2021

e20557 Background: The present study evaluates outcome after chemoradiotherapy (CRT) with concurrent and/or sequential Programmed Cell Death 1 (PD-1) or Ligand 1 (PD-L1) immune checkpoint inhibition (CPI) for inoperable stage III NSCLC patients depending on planning target volume (PTV). Methods: Prospective data of thirty-nine consecutive patients with inoperable stage III NSCLC who completed CRT with sequential durvalumab (72%, 28 patients) or concurrent and sequential nivolumab (28%, 11 patients) were analyzed. Different cut offs for PTV as well as PTV as a continuous variable were evaluated for association with progression-free survival (PFS) and extracranial metastasis-free survival (eMFS). Results: All patients were treated with conventionally fractionated TRT to a total dose of at least 60 Gy (range: 60-63.6Gy), 97% (27 patients) received two cycles of concurrent platinum-based chemotherapy. Median follow-up for the entire cohort was 23.2 (range: 6.0-42.6) months; median overall survival (OS) and eMFS were not reached. Median Progression-free survival (PFS) was 22.8 (95% CI: 10.3-35.2) months. Age (65 years), gender and UICC stage had no significant impact on PFS. There was no significant difference between durvalumab and nivolumab patients. Patients with PTV ≥ 900ccm had a significantly shorter PFS (11.77 vs 26.3 months, p = 0.049) and eMFS (11.7 months vs not reached, p = 0.019). Furthermore, patients with PTV ≥ 900ccm and stage IIIC disease (TNM 8th Ed.) achieved a dismal median PFS of only 3.6 months (vs. 26.3 months p < 0.001). PTV as a continuous variable showed a trend for association with PFS (p = 0.064) and was a significant negative prognosticator for eMFS (p = 0.030; HR: 4.065; 95%CI: 1.148-14.397). Conclusions: PTV has a significant impact on the PFS and eMFS after CRT combined with concurrent and/or sequential CPI in inoperable stage III NSCLC. Patients with PTV ≥ 900ccm had a significantly shorter PFS and eMFS.
Prognostic impact of inflammatory profiling during and after multimodal treatment for stage III NSCLC.
Authors: Käsmann Lukas , Cabeza-Boeddinghaus Natalia Christina , Taugner Julian , Eze Chukwuka , Hofer Thomas Philipp , Pelikan Carolyn , Belka Claus , Noessner Elfriede , Staab-Weijnitz Claudia , Manapov Farkhad 
Published: June 2021

e20559 Background: Immune cells have a broad impact on tumor initiation, growth, and progression, and many of these effects are mediated by proinflammatory cytokines. The prognostic impact of dynamic changes of inflammatory cytokines in non-operable stage III NSCLC patients treated with (chemo)-radiotherapy ± immune checkpoint inhibition is unknown. In a prospective analysis, pro-inflammatory cytokines including interleukin 2, 6, and 8 from peripheral blood samples were evaluated 5-10 days before treatment start (T1), on the last day of thoracic radiotherapy (T2), and 3 weeks after radiation (T3) for their impact on overall survival (OS) and progression-free survival (PFS). Methods: Twenty patients, 85% male, at a median age of 65.5 (range 33-77) years were prospectively enrolled in this study. Eighteen (90%) patients received platinum-based concurrent chemoradiotherapy (CRT); seven (35%) patients additional concurrent and/or sequential immune checkpoint inhibition (four patients nivolumab and three durvalumab); patients treated with nivolumab received induction chemotherapy. Thoracic irradiation (TRT) was applied in all patients with a median cumulative dose in equivalent 2Gy fractions (EQD2) of 64Gy (range: 52-65Gy). Results: Median follow-up achieved 25 (range 14-30) months, median OS was not reached and median PFS was 11.8 (95%CI 5.2-18.4) months. To analyze pre-treatment data, median values were used as cut-off for dichotomization. Higher IL6 levels (≥9.75pg/ml) before irradiation (T1) were associated with impaired OS (median 11 months vs. not reached; p < 0.001) and PFS (median 7.0 months vs. not reached; p = 0.041). Higher IL8 levels (≥4.62pg/ml) were also associated with shorter OS (median 16 months vs. not reached; p = 0.009) and PFS (median 7 months vs. not reached p = 0.040). Patients with a decline of ≥10% of IL8 level between T1 and T2 had a significantly shorter PFS (11.8 months vs. not reached; p = 0.028). Conclusions: High proinflammatory cytokine levels were significantly associated with deterioration of outcome regarding OS and PFS in patients enrolled in multimodal treatment for stage III NSCLC. A decline of ≥10% of IL8 level during TRT was associated with impaired PFS.
Residencial radon and small cell lung cancer: A case control study.
Authors: Rodriguez Martinez Angeles , Ruano Alberto 
Published: June 2021

e20566 Background: Residential radon is the second most important risk factor for lung cancer. We aim to asses the effect of residential radon exposure on the risk of SCLC in general population. Methods: A multicentric hospital-based case-control study was designed including 10 hospitals from Spain and Portugal. Incident cases with pathological diagnosis of SCLC were prospectively recruited. Controls consisted in patients undergoing non-complex surgery unrelated to tobacco consumption. All study participants were sent a radon detector. Results: A total of 375 cases and 902 controls were recruited. 24.5% of cases were women. The median age at diagnosis was 66 for cases. 6.4% of the cases were younger than 50 years. Tobacco consumption was higher in cases compared to controls. Residential radon concentrations were higher than 147 Bq/m3 in 161 SCLC cases (42.9%). Median residential radon concentration was also higher in SCLC cases compared to controls (152.5 Bq/m3 vs 142 Bq/m3). Those people exposed to more than 147 Bq/m3 and heavy smokers showed an OR of 72,62 (95%CI 17.95 - 499.41) compared to never-smokers with less than 50 Bq/m3. Conclusions: radon exposure seems to increase the risk of small cell lung cancer. There is a significant lung cancer risk departing from 148 Bq/m3 and there is also a linear dose-response pattern. Tobacco consumption may also produce an important effect modification for radon exposure. Those individuals exposed to high radon concentrations and heavy smokers can have a very high risk of this cancer type compared with their low exposed and never-smoking counterparts. It is necessary to increase radon awareness among citizens and administrations in order they can establish the necessary protective and mitigation measures against residential radon. Effect modification between residential radon exposure and tobacco consumption on the risk of small cell lung cancer.[Table: see text]
Role of chest radiation in extensive-stage small cell lung cancer with ipsilateral pleural effusion.
Authors: Komiya Takefumi , Powell Emily , Vu Charles , Takamori Shinkichi 
Published: June 2021

e20567 Background: Prognosis of extensive-stage small cell lung cancer (ES-SCLC) remains poor. Previous randomized trials suggested consolidation chest radiation (CXRT) has a modest survival benefit; however, its role in subgroups of ES-SCLC, especially ipsilateral pleural effusion (IPE) have not been reported and unknown. Methods: Using National Cancer Database (NCDB), 283,347 ES-SCLC cases diagnosed between 2004 and 2017 were screened. Eligible cases must have been staged with 7th edition of staging system and have information about clinical T and N stage, and minimum follow-up of one month. Role of CXRT was examined in M1a, M1b, and IPE subgroups. Surveillance, Epidemiology, and End Results Program (SEER) was analyzed to independently validate our results. Univariate and multivariate analyses were conducted with Cox proportional hazard models. A p-value < 0.05 was considered as statistically significant. Results: A total of 36,762 (5,511 with M1a, 31,251 with M1b, and 2,013 with IPE) cases were analyzed. In both M1a and IPE groups, use of CXRT was significantly associated with younger age, female sex, non-academic institution, and clinical T stage. Both univariate and multivariate analyses showed that use of CXRT demonstrated significantly longer overall survival in all the groups, with lower hazard ratios in the M1a and IPE groups than in the M1b group (univariate hazard ratio 0.62, 0.56, and 0.72, respectively). Propensity score analysis of the IPE group also showed a survival advantage in the CXRT group (hazard ratio 0.54). The SEER data also showed a survival advantage of CXRT in the IPE group (univariate hazard ratio of 0.40). Conclusions: This retrospective database analysis suggests M1a and in particular IPE subgroups have more survival benefit of CXRT than the M1b subgroup. Further studies are warranted to confirm the hypothesis.