bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemoradiation-induced pneumonitis in patients with unresectable stage III non-small cell lung cancer: A meta-analysis.
Authors: Pierce Christine , Kuang Yuting , Chang Hsiu-Ching , Nevo Arianna , Deitz Anne , Keller Steven M. , Piperdi Bilal , Uyei Jennifer 
Published: June 2021

e20532 Background: Recent clinical trials have shown positive results for therapies combining concurrent chemoradiation therapy (cCRT) and checkpoint immunotherapy in unresectable non-small cell lung cancer (NSCLC). cCRT is associated with an increased risk of pneumonitis, a severe and life-threatening inflammation of the lungs. To further inform clinical decision-making and support the evaluation of new therapies combining immunotherapies with cCRT, it is important to understand the baseline risk of pneumonitis associated with cCRT alone. The objective of this study was to quantify the incidence of cCRT-induced grade 3−5 pneumonitis (immune-mediated and radiation pneumonitis) in unresectable stage III NSCLC patients. Methods: A systematic literature review and meta-analysis were performed in accordance with PRISMA guidelines. MEDLINE, Embase, and the Cochrane Central Register were searched from 2014 to April 24, 2020. Chemotherapies of interest were cisplatin, pemetrexed, etoposide, carboplatin, and paclitaxel. Randomized controlled trials (RCTs), observational studies, and non-randomized trials were included. Bayesian meta-analysis using a binomial model random effects model was conducted with SAS 9.4. Results: Among 1,889 records identified from the search, 17 studies (6 RCTs, 8 observational studies, 3 single-arm trials) met inclusion criteria. Eleven studies were included in the meta-analysis (5 RCTs, 6 observational studies; 1,788 patients). All studies specified radiation-related pneumonitis (RP), although this is clinically indistinguishable from immune-mediated pneumonitis. Patient populations were comparable across studies; the most common chemotherapies were paclitaxel + carboplatin (n = 6) and pemetrexed + cisplatin (n = 5), and radiation doses ranged from 60–74 Gy. There was variation across studies in intervention, outcome reporting, and follow-up (median range: 12–73 months), but this variation was considered acceptable based on sensitivity analyses. The estimated pooled incidence of grade 3−5 RP in cCRT-treated unresectable stage III NSCLC patients was 3.62% [95% confidence interval (CI): 1.65−6.21] in RCTs and 5.98% [95% CI: 2.26−12.91] in observational studies. The pooled incidence of fatal (grade 5) RP was 0.37% [95% CI: 0−2.78] in RCTs and 1.73% [95% CI: 0.53−4.33] in observational studies. Conclusions: This study estimates that 3.62–5.98% of patients with unresectable stage III NSCLC develop grade 3−5 RP when treated with cCRT, with incidence varying by study design. Estimates of RP incidence were higher in the real-world setting compared to RCTs. These results can be used to contextualize the baseline risk of cCRT-induced pneumonitis in unresectable stage III NSCLC to better understand the adverse event of pneumonitis associated with novel immunotherapy treatments indicated for concomitant use with this modality.
Observed survival benefit with limited exposure of durvalumab in unresectable stage III non-small cell lung cancer at a large community-based institution.
Authors: Vadehra Deepak , Pallas Christopher R , Moore Donald , Villadolid Jeryl Jean , Robinson Myra M. , Mileham Kathryn Finch , Carrizosa Daniel R. 
Published: June 2021

e20539 Background: The PACIFIC trial ushered in a paradigm shift in the management of unresectable, non-metastatic non-small cell lung cancer (NSCLC), demonstrating improvement in 12,24,36-month overall survival (OS) and leading to the 2018 FDA approval for durvalumab in unresectable or locally advanced stage III NSCLC. With almost 3 years of FDA approval, we performed a retrospective analysis of patient experiences and outcomes at Levine Cancer Institute analyzing patient data to assess survival and potential points of clinical significance. Methods: Patients over the age of 18, who met criteria similar to the PACIFIC trial (i.e. unresectable or locally advanced stage III NSCLC) from February 2018 through September 2020 were analyzed. Those who were receiving active treatment at the data cutoff were excluded. Patient characteristics, prior treatment, durvalumab administration, immune-related adverse events (irAEs), and efficacy data were summarized and evaluated. OS and progression free survival (PFS) were evaluated with Kaplan Meier methods. Results: A total of 159 patients were evaluated. 40.9% were female and 59.1% were male. The median age was 67 (range 38-83 years). Of note, 86.8% of patients were white, whereas 13.2% were nonwhite. 50.3% patients experienced an irAE. The most common reasons for discontinuation of durvalumab were completion (at least 24 doses), progressive disease, or toxicity (33.3%, 30.8%, 26.4%, respectively). The median number of doses of durvalumab received was 14 (range 1-26 doses). The median PFS was 15.3 months with 12-and 24-month PFS being 54% and 41.1 %, respectively. Median OS was 42 months with 12-and 24-month OS being 78.1% and 67.8%, respectively. Our analysis compared outcomes in those who completed adjuvant durvalumab versus those who did not complete adjuvant therapy (Table). Conclusions: Data shows the best survival in those who completed durvalumab (comparable to historic values) and novel data shows a perceived survival benefit in those completing 12 doses compared to those who did not. Thus, partial treatment may provide a survival advantage. Further multivariate analysis will look for possible correlations to increased immune events and inability to complete therapy. Further investigation will delve into this cohort’s small proportion of non-white patients, evaluating for possible barriers to care that may lead to more patients being diagnosed with stage IV NSCLC.[Table: see text]
Molecular and clinical characteristics of primary pulmonary lymphoepithelioma-like carcinoma.
Authors: Fan Ying , Shan Qian Yun , Gong Jia Li , Qin Jing , Lu Hongyang 
Published: June 2021

e20541 Background: Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is an extremely rare subtype of non-small cell lung cancer (NSCLC) and there are no established treatment protocols due to its rarity. At present there are only limited studies about the molecular and clinical characteristics of PPLELC and the results are often inconsistent. Methods: The study collected patients with PPLELC who were admitted to Zhejiang Cancer Hospital from 2009 to 2020 retrospectively. Next-generation sequencing (NGS) was performed to obtain a more comprehensive mutation profile of PPLELE, tumor mutation burden (TMB) level and the expression of programmed cell death 1 ligand 1(PD-L1) was detected for 7 patients. In addition, we review the studies concerning the immunotherapy of advanced PPLELC. Results: 18 patients diagnosed as PPLELC pathologically were collected. 71.4% (5/7) patients expressed PD-L1 (≥ 1%) and the median TMB was 2.5 mutations/Mb. TP53 (43%) and CYLD (43%) were the two most common mutations and other variants included LRIG1 (14%), PTPRT (14%), PPP2R2A (14%). 15 patients survived, 3 patients died and 1 patient was lost after a followed up time for 8.8 to 138 months. A total of 11 cases of advanced PPLELC patients who received immunotherapy were analyzed retrospectively and the disease control rate (DCR) was 90.9%. Conclusions: The prognosis of PPLELC is better than that of other NSCLC and immunotherapy may be a promising treatment to prolong the survival time of advanced PPLELC.Whether the immunotherapy efficacy of PPLELC can be predict by PD-L1 and TMB is worthy of further clinical research. CYLD genetic alterations may participate in Epstein-Barr virus (EBV) -mediated tumorigenesis in PPLELC and expected to provide a new therapeutic target.
Treatment patterns and characteristics in the second and third-line therapy setting for real-world small cell lung cancer patients.
Authors: Prince Patricia , Estrin Adina , Supina Dylan , Ben-Joseph Rami , Boccuti Anne , Asubonteng Kobby , Rengarajan Badri , Fridman Moshe , Hanvesakul Raj , Taylor Benjamin 
Published: June 2021

e20576 Background: With emerging treatment options for small-cell lung cancer (SCLC) patients after initial treatment failure, the real-world management of this disease should be assessed. This study aims to describe treatment patterns of real-world SCLC patients in the second-line therapy (2L) and third-line therapy (3L) setting. Methods: This was a descriptive study of real-world data sourced from ConcertAI electronic medical records, including data from CancerLinQ, an initiative of the American Society of Clinical Oncology of adults (age ≥ 18 years) with confirmed SCLC between January 1, 2016 and December 31, 2018. Patients were excluded based on evidence of other primary cancer at baseline, missing stage, death prior to diagnosis, or clinical trial participation. Patients entered the cohort on their SCLC diagnosis date and were followed through three tumor progressions to assess treatment patterns. Treatment patterns were assessed in 2L and 3L. Baseline characteristics were assessed in the 6 months prior to each line. Patients were classified as having unknown treatment if they had a gap in medical records > 90 days or no recorded tumor response or death within 180 days. Results: Overall, 538 patients were identified; 131 with unknown treatment, 108 with no treatment, 299 with 1st line therapy (1L), 124 with 2L, and 44 3L. The majority (76%) of patients were diagnosed in a community hospital setting. The most common comorbidities were chronic obstructive pulmonary disease (2L 25%, 3L 16%), diabetes (2L 15%, 3L 14%), congestive heart failure (2L 7%, 3L 9%), and myocardial infarction (2L 3%, 3L 2%). Radiation therapy was commonly used in 2L and 3L (2L 48%, 3L 43%) as were immunotherapies (2L 23%, 3L 23%). The most common systemic therapy in 2L and 3L was nivolumab (19% and 16%). Topotecan accounted for 11% of patients treated in 2L and 7% of those in 3L. Conclusions: During this treatment era (pre-immunotherapy 1L approval) there were limited treatment options available for SCLC patients. Radiation therapy and immunotherapies were frequently used as 2L and 3L therapy.[Table: see text]
The prognostic impact of KRAS, TP53, STK11 and KEAP1 mutations and the influence of the NLR in NSCLC patients treated with immunotherapy.
Authors: Proulx-Rocray Francis , Routy Bertrand , Nassabein Rami Mohamad , El Ouarzadi Omar , Belkaid Wiam , Tran-Thanh Danh , Florescu Marie , Tehfe Mustapha , Blais Normand 
Published: June 2021

e21010 Background: ICIs changed the way NSCLC is treated, but not all patients benefit from it. PD-L1 level is used to predict response to therapy, but its performance is sub-optimal. KRAS is important in NSCLC tumorigenesis, but the impact of its mutations in patients treated with ICIs is unclear. Similarly, studies evaluating co-mutations in TP53, STK11 and KEAP1 as well as the NLR showed that they may predict the benefit of ICIs. Methods: We conducted a retrospective study including all consenting patients with NSCLC treated with ICIs at the CHUM between July 2015 and June 2020. OS and PFS were compared in co-mutation subgroups using Kaplan-Meier and logrank methods. Co-mutations in TP53, STK11 and KEAP1 as well as the NLR were accounted for. Overall response rate (ORR) and safety data was also compared in subgroups and will be detailed at the meeting. Results: We included 100 patients with known KRAS status. From these, 50 were wild-type ( KRASWT) and 50 were mutated ( KRASMut). The most frequent mutation was G12C (54%). Co-mutation status for TP53, STK11 and KEAP1 were known for, respectively, 40, 39 and 38 patients. Co-mutations for these genes were present in respectively 19 (47.5%), 8 (20.5%) and 4 (10.5%). Data comparing KRASMut and KRASWT showed non-significant differences in survival (median OS of respectively 21.1 vs. 17.7 months, p = 0.27). The presence of STK11 and/or KEAP1 mutations was associated with a negative impact on survival when compared with wild-type (median OS 7.4 vs 20.4 months, p = 0.001). When the presence of a KRAS mutation was compounded with STK11 and KEAP1, KRASMut (vs KRASWT) trended to a better prognosis in STK11+KEAP1WT tumors (median OS of 21.1 for KRASMut vs 15.8 for KRASWT, p = 0.15), but not in STK11+/-KEAP1Mut tumors (7.4 for KRASMut vs 7.0 for KRASWT). No influence on survival was seen in relationship to the TP53 co-mutation. Interestingly, the NLR was significantly higher with STK11 mutations (6.66Mut vs 3.59WT, p = 00012), slightly lower with TP53 mutations (3.23Mut vs 4.82WT, p = 0.047) but not impacted by KEAP1 (3.72Mut vs 4.20WT, p = 0.72) or KRAS mutations (4.32Mut vs 5.21WT, p = 0.34). Conclusions: The STK11 and KEAP1 mutations are significant adverse predictors of ICI therapy benefit. The NLR is strongly impacted by STK11 mutations but not by KEAP1 mutations suggesting marked differences in the resistance mechanism for both mutations. In STK11-KEAP1WT tumors, KRAS mutations seems to be associated with improved survival in NSCLC patient treated with ICIs.
Analysis of correlations between driver mutations and biomarkers with response to immunotherapy in patients with metastatic non-small cell lung cancer (NSCLC).
Authors: Yio Jiang , Wolf Brian , Yang Amber , Bayewitz Ashrei Y. , Xu Yiqing 
Published: June 2021

e21022 Background: Next-generation sequencing (NGS) performs genomic profiling on tumor tissue and provides information on mutations on 300+ selected genes. While driver mutations have targeted therapy options, apt therapies for passenger mutations are not clearly defined. The level of PD-L1 expression and the total mutation burden (TMB) score for NSCLC have independent predictive values in response to check-point inhibition immunotherapy. Using NGS data, we aimed to evaluate the correlations of driver mutations and other biomarkers with immunotherapy response. Methods: We performed a retrospective analysis on the NGS results for NSCLC patients treated between November 2011 and February 2018. Patients were identified from the Foundation Medicine Company database and were linked to records at our cancer center. Patients’ demographics and treatment data were assessed. Results: 99 NSCLC patients (44 males and 55 females) were included with a median age of 65 (range 32-89). Races included Asian (n=42), Caucasian (n= 40), African American (n=8), and Hispanic (n=7). 49 patients possessed driver mutations, which were EGFR (n=22), ALK (n=5), RET (n=5), ROS (n=2), BRAF (n=5), MET amplification (n=5), BRCA 1 or 2 (n=4), and NTRK (n=2); 3 patients had both a driver and a non-driver mutation. In the entire cohort, 40 patients (58 total, 69%) had PD-L1 tumor proportion score (TPS) > 0% and 31 (53%) had TPS ≥10%. 30 patients (48 total, 63%) had TMB <10 and 18 (37%) had TMB ≥10. Patients with driver mutations had a lower probability of high TMB (p=0.007), but no difference in PD-L1 expression (p=0.61). PD-L1 TPS score had no correlation with TMB high or low scores (Table). In patients with driver mutations, other mutations were detected by NGS. In EGFR+ patients, the most common additional mutations were TP53 and CDKN2A/B. 23 patients received immunotherapy; the response rate in non-mutation carriers was 45.4% (5/11). Among the 7 patients with an EGFR mutation, 4 had PD-L1 TPS ≥30% and none had TMB ≥10; based on RECIST 1.1, stable disease (SD) was the best response in 2 patients. One patient with a BRAF mutation and another patient with an ALK mutation had partial responses (PR); both had TMB ≥ 10. Conclusions: NGS provides additional information in NSCLC patients with driver mutations. In patients with driver mutations, while PD-L1 expression may not be associated with response to immunotherapy, a high TMB level may be a predictive biomarker, which warrants further study.[Table: see text]
Penpulimab in combination with anlotinib as first-line treatment in advanced nonsquamous non-small-cell lung cancer.
Authors: Han Baohui , Chen Jianhua , Wang Ziping , Li Xingya , WANG Lin , Wu Lin , Xie Qiang , Zhao Yanqiu , Wang Mengzhao , Lu Junguo , Shi Huaqiu , Ye Feng , Mei Xiaodong , Yao Weirong , Yue Lu , Jiang Da , Zhao Jian , Zhang Shucai , Chen Gongyan , Jiao Shunchang 
Published: June 2021

e21072 Background: Penpulimab is a human IgG1 monoclonal antibody (mAb) directed against human programmed cell death-1 (PD-1). Penpulimab, with its unique binding epitope, was engineered to eliminate Fc-mediated effector function that compromises anti-tumor immune cell function, and to optimize receptor occupancy by improving duration of drug binding. As a promising multi-target tyrosine kinase inhibitor (TKI), anlotinib significantly improved overall survival in advanced NSCLC patients (pts) in the phase 3 trial ALTER0303. Antiangiogenesis therapy combined with PD-1/PD-L1 inhibitors has shown excellent efficacy in advanced NSCLC pts. This is the trial evaluating chemo-free combination of penpulimab plus anlotinib in treatment-naive advanced NSCLC pts regardless of PD-L1 expression (NCT03866980). Methods: Pts with previously untreated, stage IIIB/IIIC/IV non-squamous NSCLC without sensitizing mutation of the epidermal growth factor receptor (EGFR) gene or translocation of the anaplastic lymphoma kinase (ALK) gene were enrolled. Eligible pts received penpulimab 200mg Q3W in combination with anlotinib 12mg QD (2 weeks on 1 week off) until loss of clinical benefit or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included ORR, disease control rate (DCR), duration of response (DoR) and overall survival. Results: As of January 13, 2021, 26 pts had received the combination therapy of penpulimab plus anlotinib (median age 59.5yrs [range 30-71], 76.9% male, 76.9% ECOG PS 1), with a median treatment duration of 3.5 months. Of 21 pts who have had at least one tumor assessment, the ORR was 57.1% (12 PRs) and DCR was 90.5% (12 PRs, 7 SDs). Median PFS has not been reached, and eleven responders remain in response. Treatment-related adverse events (TRAEs) occurred in 53.8% of pts (≥G3 TRAEs occurred in 15.4% [4/26]). Treatment-related SAEs occurred in 15.4% [4/26], and 7.7% of pts [2/26] had drug interruption or discontinuation due to TRAEs. Most common TRAEs (≥15%) were ALT increased, AST increased, hyperthyroidism and hypertension (15.4% each). Conclusions: The combination of penpulimab plus anlotinib as first-line treatment for locally advanced/metastatic NSCLC showed the promising efficacy with a manageable safety profile, thereby suggesting that this combination therapy may be a viable chemo-free treatment strategy for locally advanced/metastatic NSCLC pts. Clinical trial information: NCT03866980.
The effect of sex and BMI on outcomes in patients with metastatic non-small cell lung cancer treated with immunotherapy.
Authors: Jin Jingxiao , Visina Jacqueline , Burns Timothy F. , Diergaarde Brenda , Stabile Laura P. 
Published: June 2021

e21085 Background: Recent studies suggest that among non-small cell lung cancer (NSCLC) patients treated with immunotherapy (IT), those who are male and/or have higher body mass index (BMI) benefit most; however, the role of other factors such as pretreatment weight loss is not clear. We conducted a retrospective study to further characterize the relationship between sex, BMI and response to IT in NSCLC. Methods: Patients with stage IV NSCLC treated with IT between 2017 and 2019 at UPMC Hillman Cancer Center were included. Demographic and clinical data were obtained from medical records. Chi-square test was used to compare baseline patient characteristics, best response (CR, PR and SD vs. PD), and presence of immune-related adverse events (iRAEs) between BMI and sex categories. Cox proportional hazards models were used to assess the effect of BMI and sex on progression free survival (PFS) and overall survival (OS). Analyses were conducted overall as well as stratified by treatment regime (1st line monotherapy, non-1st line monotherapy, and concurrent chemotherapy). Results: The study population consisted of 297 patients; 50.2% female (N=149), 87.8% white (N=261), and mean age at IT initiation 68 yrs (range: 36-91 yrs). Median follow-up time: 21 months. At IT initiation, 27 patients were underweight (BMI <18.5), 107 normal weight (BMI 18.5-24.9), 96 overweight (BMI 25-29.9), and 67 obese (BMI ≥30). Among underweight patients, weight loss pretreatment (≥10 lbs) was significantly more common ( P=0.02), and response to IT significantly worse (33% vs 61% good response; P=0.005) compared to those with BMI ≥18.5. No significant difference in response was observed between normal, overweight and obese patients, nor between men and women. The presence of iRAEs did not differ by BMI or sex. Females had better OS than males [HR (95%CI): 0.65 (0.47-0.90)] but PFS was similar. In stratified analyses, better OS among females was limited to the concurrent chemotherapy group [0.52 (0.30-0.92)]. Overall, underweight patients had worse OS than those with BMI ≥18.5 [1.71 (1.01-2.92)]; this was not significant after adjusting for pretreatment weight loss [1.48 (0.87-2.53)]. No difference was observed in OS and PFS between normal, overweight and obese patients. In stratified analyses, underweight individuals had worse OS [4.12 (1.55-10.94)] and PFS [3.87 (1.44-10.38)] than those with BMI ≥18.5 when treated with 1st line monotherapy. Weight loss pretreatment was independently associated with worse OS [2.20 (1.51-3.20)] and PFS [1.47 (1.05-2.05)]. Conclusions: In contrast to prior reports, NSCLC patients receiving IT did not benefit from higher BMI or male sex. Females treated with concurrent chemotherapy had improved OS, and pretreatment weight loss was an indicator of poor prognosis. Further study is required to understand the pathobiology behind these predictors.