bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD-L1 expression and progression risk of stage III NSCLC patients on durvalumab consolidation.
Authors: Jazieh Khalid , Gad Mohamed , Saad Anas M , Pennell Nathan A. 
Published: May 2020

e21070 Background: Durvalumab is an anti-PD-L1 agent used as consolidation for patients with stage III non-small cell lung cancer (NSCLC) following chemoradiation. In the PACIFIC trial similar progression-free survival (PFS) and overall survival (OS) benefits were seen whether patients had PD-L1 expression of ≥25% or <25%. In this study we sought to examine outcomes for patients with PD-L1 expression using the more commonly used <1%, 1-49%, and 50-100% cutoff points. Methods: This was a retrospective analysis of 52 patients with stage III NSCLC who underwent treatment with chemoradiation followed by durvalumab maintenance. Patients were divided into groups of PD-L1 Negative (<1% positivity), Low PD-L1 (1-49%), and High PD-L1 (50-100%) based on the percentage of tumor PD-L1 expression using local testing with the Dako 22C2 antibody. The primary endpoint was presence or absence of radiographic progression while on durvalumab or after completing therapy, while PFS and OS were also determined. Results: Of the 52 patients, 25% were in the High PD-L1 group, 21% in the Low PD-L1 group, 27% in the PD-L1 Negative group, and the remaining were not tested for PD-L1. The progression rates were 64.3%, 90.9%, and 23.1% for the PD-L1 Negative, Low PD-L1, and High PD-L1 groups respectively (Table). Using Chi-square analysis there was a significant association between the extent of PD-L1 expression and progression (p = 0.003). The odd’s ratio (OR) of progression in the High PD-L1 group compared to the PD-L1 Negative group was 0.167 (0.031-0.904, p = 0.038), and the OR of progression in the Low PD-L1 group compared to PD-L1 Negative was 5.556 (0.541-57.00, p = 0.149). There was a statistically significant difference in PFS between the groups (p = 0.019), but not OS. Conclusions: Our results show that PD-L1 expression may be useful in predicting the risk of cancer progression in stage III NSCLC patients undergoing durvalumab consolidation. Patients with high PD-L1 (50-100%) expression had significantly lower odds of disease progression and longer PFS compared to those who were negative for PD-L1. While the rate of progression was higher in the Low PD-L1 group, the OR was not statistically significant when compared to the PD-L1 Negative group. [Table: see text]
Trends in management of locally advanced large cell neuroendocrine carcinoma of the lung.
Authors: Limonnik Vladimir , Abel Stephen , Colonias Athanasios , Monga Dulabh K. , Finley Gene Grant , Wegner Rodney E. 
Published: May 2020

e21073 Background: Large cell neuroendocrine carcinoma (LCNEC) is a rare pulmonary malignancy with clinicopathologic features of both non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). The optimal treatment approach for LCNEC is not well established, likely a result of the histology’s underrepresentation in randomized clinical trials. Given the paucity of available data regarding LCNEC management, we queried the National Cancer Database (NCDB) to describe trends in management, identify predictors of treatment receipt, and compare outcomes in patients receiving chemotherapy (ChT) and chemoradiotherapy (CRT). Methods: We identified patients with locally advanced (Stage III) LCNEC of the lung treated with definitive ChT or CRT between the years of 2004-2015. Odds ratios were calculated to determine predictors of CRT receipt. Multivariable cox regression was used to determine predictors of overall survival. Results: Using the above criteria, 6,802 patients were identified, 46% of whom received CRT (n = 3,153) while 39% (n = 2,644) received ChT alone. Median age of the entire cohort was 68 years old. Most patients had T4 (35%) and N2 (59%) disease. Median overall survival was 11.9 months (11.3-12.6) in patients receiving ChT compared to 16.1 months (15.4-16.9) in patients receiving CRT (p < 0.0001). Overall survival at 1, 3, and 5 years was 50%, 20%, and 13% versus 60%, 27%, and 18%, in patients receiving ChT and CRT, respectively. Older patients and those with higher comorbidity scores were less likely to receive CRT; whereas patients with higher education level, treatment receipt at an academic/research program facility, N2 disease, and later treatment year were more likely to receive CRT. On multivariable analysis, older age, greater comorbidity score, presence of N2 disease, and presence of T4 disease were all associated with decreased OS, whereby female sex, private insurance, higher income, lower T stage, and more recent treatment were associated with increased overall survival. CRT receipt was an independent predictor of increased overall survival. Conclusions: Definitive CRT was an independent predictor of increased overall survival in patients with locally advanced LCNEC of the lung. Findings from our study may help guide potential areas of future investigation to help define an ideal treatment approach for LCNEC.
Stereotactic body radiotherapy and systemic dose chemotherapy for locally advanced lung cancer, single-arm phase II study.
Authors: Kubicek Greg , Khrizman Polina , Squillante Christian Michael , Xu Qianyi , Abouzgheib Wissam , Boujaoude Ziad , Patel Ashish Bharat , Hageboutros Alexandre 
Published: May 2020

e21081 Background: The outcomes for locally advanced non-small cell lung cancer (NSCLC) are overall poor. This is a single arm phase 2 study (Clinical trials.gov NCT02568033) evaluating the role of stereotactic body radiosurgery (SBRT) along with full dose systemic chemotherapy in the treatment of unresectable stage 2 and stage 3 NSCLC. Methods: patients were treated with SBRT to all sites of gross disease. Dosing consisted of 60 Gy in 3 fractions for peripheral lung tumors, 50 Gy in 5 fractions for central lung tumors, and 40-50 Gy in 5 fractions for hilar and mediastinal lymph nodes. Chemotherapy was histology dependent and consisted of 4 cycles, there was a 7 days break between chemotherapy and SBRT. Quality of life was measured using FACT-L. Results: Twenty two patients were enrolled and analyzed. 17 (77 %) were stage III and 19 (86%) had lymph node involvement. Median follow-up for all patients was 23.1 months. Median overall survival is 27.2 months. Overall survival at one year was 82% and overall survival at two years was 53%. Two year regional failure rate 19%. Two year distant failure rate 47.2%. Quality of life scores at one year were available for 12 patients and were unchanged compared to baseline. Acute toxicity grade 3 or greater was seen in 6 patients and late toxicity grade 3 or higher was seen in 2 patients. Conclusions: A combination of SBRT and full dose chemotherapy appears to be a safe and effective treatment for locally advanced NSCLC and warrants further investigation. Clinical trial information: NCT02568033 .
Mutational distinction between adenocarcinoma in situ, minimally invasive adenocarcinoma and invasive adenocarcinoma in lung cancer patients with multiple tumors.
Authors: Liu Jixian , Li Yingmei , Xie Yuancai , Luan Xinyu , Peng Xuxing , Mu Tianhao , Chen Shifu , Wu Da 
Published: May 2020

e21089 Background: Lung adenocarcinoma is the most popular lung cancer type, and it can be classified as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IA) based on histology. The mutational similarities and differences have not been discussed in these subtypes. Methods: Targeted deep sequencing was performed on 31 lung adenocarcinomas with matched blood samples from 15 patients with multiple tumors. We compared mutations among each subtype. Results: The 31 tumors consisted of 10 AIS, 6 MIA and 15 IA subtypes; the median mutation number in each type was 1, 1 and 3 respectively. Eleven, six and fifty-three mutations were identified in AIS, MIA, and IA respectively. Among all the 67 mutations, only EGFR_p.L858R was found in all three types; BRAF_p.K601E was found in AIS and IA. Conclusions: AIS, MIA and IA harbor distinct mutational signatures, except for several popular driver mutations, suggesting their distinct origin and evolution path.
A single-center retrospective cohort study evaluating the role of neoadjuvant chemotherapy in malignant peritoneal mesothelioma.
Authors: Wang Xiao , Katz Sharyn I. , Roshkovan Leonid , Walker Suzanne , McNulty Sally , Ciunci Christine Agnes , Muira John , Karakousis Giorgos , Cengel Keith A. , Langer Corey J. , Marmarelis Melina Elpi 
Published: May 2020

e21093 Background: Malignant peritoneal mesothelioma (MPM) is a rare variant of malignant mesothelioma, representing < 30% of cases. Standard of care is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) when feasible. The benefit of systemic chemotherapy (chemo) (Neoadjuvant- N, Adjuvant- A, or 1st-line metastatic –M) is not well established and some retrospective studies report worse outcomes with N chemo. However, our institution has favored use of N chemo prior to surgery for symptom relief and surgical optimization. We conducted a single-center retrospective cohort study of MPM patients treated at our institution to evaluate the effect of N vs. A chemo on outcomes. Methods: We identified non-papillary MPM patients via ICD9/10 codes seen at our institution between 1/1/2009 and 9/1/2019. Pts were followed until 1/1/2020. Patients without pathologic diagnosis were excluded. We explored the effect of receipt of CRS, type of systemic therapy, and histology on overall survival. Median overall survival (mOS) from diagnosis was estimated from Kaplan-Meier curves. A Cox proportional hazard model computed hazard ratios (HR) to assess the effect of the exposure on OS. Results: We identified 47 patients with non-papillary MPM: median age 62 years, 77% epithelioid histology, 74.5% white, 55.3% known asbestos exposure. CRS was performed in 24 (51%) and 18/24 (75%) received HIPEC. The majority received systemic therapy (34/47 (72%)). Among those that received chemo and surgery, N chemo was more common than A chemo (N:12 (all platinum/pemetrexed), A:7). Median OS was 52.7 months (mo) overall and 77.2 mo with surgery vs 20.2 mo without (log rank p = 0.006). Toxicity from N chemo did not prevent surgery with 8/12 successfully receiving surgery (1 surgery scheduled, 2 lost to follow up). Of the 10 pts with evaluable scans: 5 had radiographic reduction of disease (2 complete responses by RECIST 1.1), 4 stable disease and 1 with disease growth. N chemo reduced ascites in 3 out of 4 pts with baseline ascites. N chemo was not associated with worse mOS compared to A chemo (HR 0.64, 95% CI 0.1-3.0, p = 0.62). Non-epithelioid histology was not associated with a worse OS compared to epithelioid (HR 1.5, 95% CI 0.6-4.1, p = 0.4). Conclusions: N chemo was not associated with worse outcomes compared to A chemo and toxicity from N chemo did not preclude surgery. In addition, N chemo resulted in reduction of disease burden and ascites in pts with MPM.
Identifying genomic alterations in small cell lung cancer using the liquid biopsy of bronchial washing fluid.
Authors: Zhai Jinfang , Han Songyan , Guo Qinxiang , Shan Binbin , Wang Jing , Guo Yanrong , Tong Guoping , Zhao Chang , Li Yuan , Han Qiao , An Xiaoqin , Yue Ruiqing , Wang Li , Guo Tingting , Yang Weihua 
Published: May 2020

e21098 Background: With the rapid development of cancer genomics, the precision medicine of small cell lung cancer (SCLC) is emerging. However, there are limitations to the clinical use of tumor tissue and peripheral blood biopsies. The main purpose of this study was to evaluate the potential use of bronchial washing fluid (BWF) in the liquid biopsy of SCLC. Methods: Twenty-one SCLC patients diagnosed in 2019 were enrolled in this study. BWF (separated as supernatant and precipitate), treatment-naive plasma and tumor tissue samples were collected from all of patients and subjected to next-generation sequencing (NGS) using a 1021-gene panel. The concordance rates of genomic profiling using NGS in these four types of samples were evaluated. Results: Of these 21 patients, 20 BWF supernatant (BWFs) samples, 21 BWF precipitate (BWFp) samples, 21 tumor tissue samples and 20 plasma samples were successfully tested. The detectability of somatic mutations was 100% for BWFs, BWFp and tumor tissues, and only one plasma was absent with any mutation. Matched tumor tissue, BWFs, BWFp and plasma samples were subsistent for 19 patients. For these patients, 204 genomic alterations were identified in tissue samples, of which 189 (92.6%), 175 (85.5%) and 163 (79.9%) alterations were detected in the matched BWFs, BWFp and plasma samples, respectively. Moreover, tumor mutation burden (TMB) was also calculated. Compared with the proportion of TMB-H samples in tissue samples counting 61.9% (13/21), 60% (12/20) of BWFs samples and 52.38 % (11/21) of BWFp samples were TMB-H (defined as more than or equal to 9 mutations per megabase), which was a molecular biomarker that can be used in immunotherapy efficacy prediction. The TMBs of BWFs, BWFp and treatment-naive plasma samples all had strong correlation with that of tissue samples. The TMB of BWFs had the strongest correlation (Pearson r = 0.9512, p < 0.0001), and the TMB of treatment-naive plasma had relatively lower correlation (Pearson r = 0.8782, p < 0.0001) compared with those of BWFs (Pearson r = 0.936, p < 0.0001) and BWFp (Pearson r = 0.8782, p < 0.0001). Conclusions: For SCLC patients, the liquid biopsy of BWF showed high potential to identify DNA alterations and calculate TMB grades, which suggested that genomic analysis of BWF liquid biopsy may have clinical value in predicting the effectiveness of targeted therapy and immunotherapy. It can be widely used in routine clinical practice.
Genetic landscape and PD-L1 expression of Chinese patients with small cell lung cancer.
Authors: Chen Meifang , Zhang Ding , Wang Guoqiang , Wang Bijiong 
Published: May 2020

e21099 Background: Small cell lung cancer (SCLC) is a highly aggressive carcinoma of the lung. Whereas, precise treatment options for SCLC are limited. Genomic profiling would be essential to understand drug resistance related mechanism. So far, little is known about an in-depth molecular characterization for SCLC in Chinese patients. Here we described the mutational landscape and programmed cell death-1 (PD-L1) expression profile in Chinese patients with SCLC by next-generation sequencing (NGS) assay. Methods: Chinese patients with SCLC were included in this study. Genomic profiling of DNA was performed on formalin-fixed paraffin-embedded tumor samples and matched blood through a NGS with 381 cancer-related genes panel. PD-L1 expression status of tumor tissue was determined by immunohistochemistry. Results: In total, 115 patients with SCLC were included in the present study. We identified 2,948 mutations, spanning 434 genes, with TP53, RB1 and LRP1B being the most frequently mutated genes, occurring in 109(94.78%), 88(76.52%) and 48(41.74%) of SCLC patients, respectively. For somatic single nucleotide variant (SNV), TP53 (108/115, 93.91%), RB1 (82/115, 71.30%) and LRP1B (43/115, 37.39%) were frequently mutated, which exhibited the similar mutation frequencies with TCGA database. To be noted, 79 (68.70%) SCLC patients harbored both RB1 and TP53 mutations, which was comparable with TCGA data (84/110, 76.36%). Germline SNV spectrum varied significantly compare with somatic SNV. BLM, MSH2 and VEGFA were the most frequently germline mutated genes. In our dataset, the tumor mutation burden (TMB) of 108 patients, PD-L1 expression status of 95 patients and microsatellite stabilities/instabilities (MSS/MSI) status of 112 patients were also analyzed. The median TMB was 10.61/MB. The positive rate of PD-L1 expression was 12.63%. All patients were MSS. Conclusions: Our study revealed the genetic landscape and PD-L1 expression of SCLC. The data may provide the support on immunotherapy and targeted therapy research.
First-line apatinib plus chemotherapy in extensive-stage small-cell lung cancer.
Authors: Shi Jian , Liu Jiayin , Duan Xiaoyang , Huang Guanglei , Wang Lixing , Zhao Yan 
Published: May 2020

e21104 Background: Angiogenesis plays a critical role in the growth, progression, and metastasis of numerous solid tumor types. Apatinib is a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR2), which is inhibits tumor angiogenesis. Etoposide plus cisplatin is a standard chemotherapy regimen for Extensive-Stage Small-Cell Lung Cancer (SCLC). Combining apatinib with chemotherapy may have a synergistic effect and improve efficacy. Methods: Eligible patients were adults with histologically or cytologically confirmed extensive-stage small-cell lung cancer, excluded patients with symptomatic brain metastases. Measurable extensive-stage small-cell lung cancer according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Eligible patients were received six 21-day cycles of apatinib (250mg, orally daily) and chemotherapy (etoposide:100 mg/m2, ivgtt d1-3 of each cycle; cisplatin: 80 mg/m2, ivgtt d1 of each cycle), followed by local radiotherapy, apatinib (250mg, orally daily) maintenance therapy. For patients who have received treatment less than 6 cycles have disease progression, change the chemotherapy regimen combined with local radiotherapy. Primary endpoint: 6-month ORR. Secondary endpoints: 6-month DCR, PFS, safety. Results: We enrolled 40 patients between November 15, 2017 and April 18, 2019. Median age was 56 (range 28-67), 92.5% had an ECOG PS of 0. At the data cutoff (December 31, 2019), 27 patients were evaluated. In 27 patients who received apatinib for 4-26 months, with average of 10.6 months. The 6-month ORR was 63%, DCR was 85% [17 PR, 6 SD]. 9 patients (33.3%) achieved PFS, of which 8 patients progressed within 9 months and 1 patient progressed within 22 months. Patients who progressed within 6 months, the average duration of apatinib was 5.1 months. During the therapy, adverse events (AEs) were mostly Common grade 1-2 related AE, hypertension (37%), hand-foot syndrome (3.7%), and Hepatic Insufficiency (7.4%). Conclusions: Our study suggests that oral apatinib plus chemotherapy should be considered an active and safe treatment in patients with first-line treatment of extensive-stage small-cell lung cancer.
Atezolizumab and platinum-based chemotherapy in extensive-stage small cell lung cancer: A single center experience.
Authors: JAKOPOVIC MARKO , Bitar Lela , Krpina Kristina , Seiwerth Fran , Marusic Ante , Plestina Sanja , Kukulj Suzana , Roglic Mihovil , Korsic Marta , Badovinac Sonja , Samarzija Miroslav 
Published: May 2020

e21110 Background: In extensive stage small-cell lung cancer (ES-SCLC) immune check-point inhibitors, atezolizumab and durvalumab, when combined with chemotherapy in the first-line setting show better efficacy than chemotherapy alone with safety profile similar as the adverse events of individual agents. Methods: We administered atezolizumab, etoposide and platinum, either carboplatin or cisplatin, in the first-line treatment in 24 newly diagnosed patients with ES-SCLC. Patients were treated until disease progression or unacceptable toxicity. Results: Out of 24 treated patients 13 were males and 11 were females, median age 61 (ranging from 44 to 80). Majority of patients were ECOG 1. Median number of atezolizumab doses was 8 (ranging from 2 to 11). We observed median progression free survival of 6 months (95%CI 4,28-7,72), while median overall survival was not reached. 10 patients (41%) are still undergoing treatment and 9 patients (37%) have died. Immune-related adverse events occurred in 6 patients (25%). Four patients developed pneumonitis (all of them CTCAE grade 2), two patients colitis (CTCAE grade 2 and 3) and one patient rash, CTCAE grade 3. Median treatment pause was 5 weeks (ranging from 3 to 12 weeks). There were no treatment discontinuations due to adverse events nor treatment related deaths. Conclusions: Atezolizumab combined with chemotherapy in ES-SCLC showed good tolerability and effectiveness in real world setting. Our data are consistent with published clinical trial data. There was no new safety signal in our patient cohort. Limitations of our report are small sample size and short follow-up time.
Effect of personalized approach to therapy in non-small cell lung cancer (NSCLC) with liver metastasis with immunotherapy on outcomes.
Authors: Badin Kristine , Waseem Bushra , Ullah Asad , Abdel Karim Nagla Fawzy , Eldessouki Ihab , Guttery Boyd 
Published: May 2020

e21504 Background: Patients with NSCLC with liver metastasis tend to have significantly reduced overall survival (OS) compared to NSCLC with metastasis to other sites. We aimed looking at the patients with lung cancer at our institution over a five year period and assess the outcome of NSCLC with liver metastasis based on different treatment modalities. Methods: This is a retrospective study of patients with NSCLC and liver metastasis over the past five years. Patient data was securely collected and stratified based on demographics, histology, driver mutation analysis, date of diagnosis, place of metastasis, date of treatment, types of treatment received, and date of death, as applicable. Results: Eight of 132 patients had liver metastasis. Out of which one had SCLC and was treated with carboplatin-etoposide-atezolizumab with OS of 17 months. Remaining seven were NSCLC where five patients had adenocarcinoma and 2 had squamous histology. Pembrolizumab was part of treatment for all 4 patients with adenocarcinoma. 5th patient was treated with chemotherapy and had OS of 2 months. Female to male ratio 3:2 for adenocarcinoma and 0:2 for squamous histology with equal ethnic distribution. Two patients had squamous histology, both males and had average OS of 4.5 months. Conclusions: Patients with liver metastasis regardless of the histology, have short overall survival. However it was observed that such patients when treated with immunotherapy as part of their treatment modality do much better compared to those who did not. Specifically immunotherapy benefits are more pronounced in patients with adenocarcinoma histology compared to squamous. However further studies are indicated to evaluate personalized approach to therapy in NSCLC with liver metastasis. Our study was limited based on our limited number of patients.