bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-life experience of rare hepatoid adenocarcinomas of the lung: A large retrospective french cohort.
Authors: Favé Thomas , Quere Gilles , Robinet Gilles , Babey Hélène , Renaud Emmanuelle , Dhamelincourt Estelle , Nguyen Jessica , Simaki Amah Arnaud , Basse Victor , Descourt Renaud , Geier Margaux 
Published: June 2022

e21091 Background: Hepatoid adenocarcinoma of the lung (HAL) is a rare subtype of lung cancer exhibiting common histological features with hepatocellular carcinomas (HCC). Therapeutic landscape is currently similar to lung adenocarcinoma standards. We report here the largest descriptive cohort of HAL with focus on (chemo)-immunotherapy (CT-IO) efficacy. Methods: In this single-center retrospective observational study, we selected all consecutive cases of HAL patients from January 2013 to January 2022. Eligible patients had primary lung tumor with positive immunohistochemical hepatocyte marker. HCC was eliminated with liver imaging. We provide a descriptive analysis of HAL population and describe our therapeutic experience. Results: A total of 21 patients were included. Main characteristics at diagnosis were: median age of 63 years [41-81], 80,9% of males, with 76,2% of PS 0-1. All patients had smoking history, with 8 active smokers. Twenty patients (95,2%) had stage IV disease. Median number of metastatic sites was 2; 7 (33,3%) patients had brain metastases. PD-L1 status was < 1% (n = 10), 1-5% (n = 2), ≥50% (n = 5), unknown (n = 4). Six (28,6%) patients harbored KRAS mutation: G12C (n = 4), G60D (n = 1), G12V (n = 1). One patient had Lynch syndrome with MMR deficiency. Median follow-up was 5 months. Median overall survival (mOS) since diagnosis achieved 9 months (95% CI, 3 to 21). Early palliative care concerned 6 patients. Five patients received first-line CT-IO. Best response was: partial response (n = 3), stable disease (n = 1), progressive disease (n = 1). One patient treated with first-line pembrolizumab achieved stable disease. Four patients received second-line IO but experienced early progressive disease. Conclusions: Our results highlighted the aggressive metastatic profile of HAL accounting for the poor mOS of 9 months. Patients could benefit from upfront CT-IO but further studies are warranted to confirm it.
Immunotherapy plus chemotherapy versus chemotherapy alone as first-line treatment for non-small cell lung cancer: A systematic review and meta-analysis.
Authors: Abdelazeem Basel , Abbas Kirellos Said , Labieb Fatma , Arida Abdul Karim , El-Shahat Nahla Ahmed , Shehata Joseph , Kandah Emad , Malik Bilal , Akanbi Maxwell Oluwole , Rafae Abdul , Tahir Nayha , Wahab Ahsan , Ehsan Hamid 
Published: June 2022

e21092 Background: There is an emerging role of immunotherapy plus chemotherapy (ICC) in the front-line setting for the treatment of Non-Small Cell Lung Cancer (NSCLC) with reported improvement in overall survival (OS) and progression-free survival (PFS). In this review, we highlighted the efficacy and safety of combination regimens as a first-line therapy for NSCLC. Methods: A comprehensive literature search was done on PubMed, Cochrane, Embase, WOS, and Scopus until Dec-2021. The outcomes included progression free survival (PFS) and/or overall survival (OS) and treatment-related adverse events (TRAEs). The inverse variance method was used to generate hazard ratios (HR) with the corresponding 95% confidence intervals for the OS and PFS. Meanwhile, Mantle-Hazard variance was used to create risk ratios for TRAEs. Results: The total eleven randomized controlled trials (RCTs) involving 6,386 patients (pts) were included. 3,850 pts received ICC while 2536 pts received chemotherapy., Four studies each used atezolizumab and pembrolizumab while one study each used nivolumab, tislelizumab, and camrelizumab. The ICC group showed a significant improvement in both PFS (HR, 0.60; 95% CI, 0.54-0.66; p = < 0.00001) and OS (HR, 0.77; 95% CI, 0.68-0.87; p = < 0.0001). Atezolizumab combinations have better PFS and OS compared to the other combinations; HR 0.65 (0.59-0.71) and 0.82 (0.74-0.90), respectively. There was no statistically significant difference between the ICC and control groups regarding TRAEs (RR, 1.07; 95% CI, 0.99-1.16; p = 0.09). Further subgroup analysis is mentioned in the table. Conclusions: The ICC seems to be a promising front-line therapy for NSCLC with superior PFS and OS compared to chemotherapy alone and without significant increase in TRAES. [Table: see text]
Prognostic value of PIOS (Patras Immunotherapy Score) model in patients with advanced NSCLC treated with combination of immunotherapy with chemotherapy: Preliminary results from a European retrospective study.
Authors: Dimtrakopoulos Foteinos-Ioannis D. , Christopoulos Petros , Elshiaty Mariam , Daniello Lea , Pyrousis Ioannis , Kottorou Anastasia E , Makatsoris Thomas , Kalofonos Haralabos , Koutras Angelos 
Published: June 2022

e21096 Background: Ιmmune checkpoint inhibitors (ICIs) have tremendously changed the daily clinical practice on the treatment of advanced non-small cell lung cancer (aNSCLC). However, clinical useful biomarkers remain an unmet need. Recently, a new score, Patras Immunotherapy Score (PIOS), has been proposed by our group proving its prognostic value in aNSCLC patients treated with ICIs monotherapy. The objective of the current study was to assess the clinical significance of PIOS formula in aNSCLC patients treated with combination of immunotherapy with chemotherapy. Methods: PIOS is a baseline formula derived by combining the following non-interventional clinical parameters, Performance Status (PS), Body Mass Index (BMI), age and Line Of Treatment (LOT) and it is calculated as PIOS = (PS×BMI)/(LOT×AGE). In the current study, 159 aNSCLC patients, treated with combination of immunotherapy with chemotherapy, were retrospectively selected, blindly to the clinical outcome, and enrolled. In addition, a second subcohort with 444 aNSCLC patients, who had been treated with chemotherapy alone, were also retrospectively included. The primary endpoint of this study was to investigate the prognostic value of PIOS in terms of progression free survival (PFS) and overall survival (OS). Results: Patients with higher PIOS score had longer PFS compared to patients with lower PIOS score (ΗR 0.575, 95% CI 0.364-0.908, p= 0.016), while multivariate analysis for PFS, adjusted for PD-L1, confirmed the clinical value of PIOS score (HR 0.561, 95% CI 0.352-0.893, p= 0.015). Moreover, PIOS score was also associated with prognosis ( p= 0.003). The median OS for the favorable group was 1067 days compared to 528 days for the unfavorable group with low PIOS score (HR 0.487, 95% CI 0.302-0.787, p< 0.001) at univariate analysis. This association remained statistically significant (HR 0.468, 95% CI 0.286-0.764, p= 0.002) after adjusting for PD-L1 expression. Specificity of PIOS formula was also confirmed in the second cohort (n = 444) of patients with metastatic disease who had been treated with chemotherapy alone, in which no prognostic significance for PIOS was observed. Conclusions: This study for the first time documents the prognostic significance of PIOS model in aNSCLC patients treated with immunotherapy/chemotherapy combination and provides adequate evidence regarding the specificity of this association, since no similar finding was observed in the patients treated with chemotherapy alone.
Clinical outcomes of immune checkpoint inhibitors in HER2-amplified non-small cell lung cancers.
Authors: DeMatteo Raymond , Goldman Debra A. , Lin Sabrina T. , Buonocore Darren J. , Gao JianJiong , Chang Jason C. , Rekhtman Natasha , Offin Michael , Yu Helena Alexandra , Isbell James M. , Jones David Randolph , Rudin Charles M. , Travis William D. , Kris Mark G. , Drilon Alexander E. , Arcila Maria E. , Ginsberg Michelle S. , Iasonos Alexia , Liu Dazhi , Li Bob T. 
Published: June 2022

e21098 Background: HER2 (ERBB2) amplification is a distinct actionable oncogenic driver in 2-3% of non-small cell lung cancer (NSCLC). While HER2-targeted agents are now in development for lung cancers harboring HER2 mutations, the therapeutic landscape for patients with HER2 amplification is not well elucidated. Although immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy are widely used as treatment for NSCLC, little is known about the impact of ICIs in patients with HER2-amplified NSCLC. This study aimed to assess the efficacy of ICIs in this patient population. Methods: Patients with HER2-amplified NSCLC were identified from January 2014 to October 2021. HER2 amplification was detected by next generation sequencing (NGS) on the MSK-IMPACT platform. Clinicopathologic and molecular features, as well as response to therapy with ICIs were assessed. Patients were excluded if they harbored concurrent HER2 mutations, had localized disease, or received concurrent chemotherapy. Patient records were reviewed to evaluate overall survival (OS), progression free survival (PFS) and overall response rate (ORR). Results: Eighteen patients with metastatic HER2-amplified NSCLC who received ICI alone as first line treatment or subsequent therapy after progression met inclusion criteria. Histologic subtypes included adenocarcinoma (78%) and squamous cell carcinoma (22%). PD-L1 expression was available for 16 patients, with 69% having no expression of PD-L1. The median tumor mutation burden (TMB) was 9.2 mutations/Mb (range 3.0-35.4). The median OS was 11 months (95% CI: 4 to 37), with 6-month and 12-month survival being 67% (95% CI: 40% to 83%) and 49% (95% CI: 25% to 70%), respectively. Median PFS was 2 months (95% CI: 1 to 7). In the 15 patients that were assessed for response, the ORR was 0% (95% CI 0% to 19%), including 3 cases with PD-L1 expression of ≥ 50% and 9 cases with TMB ≥ 10 mutation/Mb. Conclusions: Patients with HER2-amplified NSCLC showed minimal response to immunotherapy, regardless of PD-L1 status and TMB. These findings underscore the importance of developing novel HER2-targeted agents for these patients with unmet medical need.
Metastatic patterns plus clinical and molecular characteristics of ROS1 aberrations in non-small cell lung cancer patients without rearrangements.
Authors: Glaser Moritz , von Levetzow Cornelia , Michels Sebastian Yves Friedrich , Nogova Lucia , Katzenmeier Marianna , Wompner Claudia , Schmitz Jaqueline , Bitter Elisabeth , Terjung Inken , Passmann Elke , Schaufler Diana , Eisert Anna , Fischer Rieke Nila , Riedel Richard , Weber Jan-Phillip , Hahne Sabine , Merkelbach-Bruse Sabine , Büttner Reinhard , Wolf Juergen , Scheffler Matthias 
Published: June 2022

e21117 Background: Fusions in the ROS1 proto-oncogene are among the best treatable genetic aberrations in Non-small cell lung cancer (NSCLC). Besides the occurrence of solvent-front mutations (SFM) in acquired resistance to targeted therapy, little is known about ROS1 aberrations other than fusions. We analyzed molecular and clinical characteristics and metastatic patterns of ROS1 mutations in NSCLC patients without activating ROS1 fusions or SFMs. Methods: Next-generation sequencing (NGS) was performed on tissue samples from NSCLC patients within the National Network Genomic Medicine (nNGM). Patients with activating ROS1 fusions detected by fluorescence in-situ hybridization (FISH) were excluded. Staging and restaging procedures were performed following local standards from each partner. We analyzed the mutations’ characteristics, co-occurring mutations and metastatic patterns. Results: Of 8072 patients analyzed by NGS between 2018 and 2021, 118 (1.5%) patients harbored ROS1 mutations. Most patients were male (76.3%) and had adenocarcinoma histology (57.6%). The median age at diagnosis amounted to 68 years. Nearly all of the patients (96.5%) had a smoking history, amassing 40 pack-years on average. Besides TP53 mutations (61.0%), KRAS (25.4%), EGFR (7.6%), PIK3CA and FGFR1-4 mutations (5.9% each) co-occurred most frequently. In 12 (10.2%) patients, ROS1 mutation was the only detected aberration. The majority (59.3%) of patients had UICC stage IV whereby 27.2% of patients featured Stage III; about 7% fall upon stage I and II. The metastatic pattern of all stage IV patients shows that 22.9% of metastasis is allotted to cerebral, 12.5% to lung, 16.7% to subdiaphragmatic, 14.9% to bone and 6.3% to skin metastasis. Thereby, the patients’ subgroup with mutually exclusive ROS1 mutations (10.2%) resembles this trend: about a half of these patients had UICC stage IV, too, and the metastasis distribution featured similar characteristics. Conclusions: The cohort contrasts the clinical characteristics of patients with ROS1 fusion regarding sex, age, and histology. This evidence implies a basic clinical impact exerted by this molecular subtype. We warrant further research on the detected mutations to characterize the biological impact and the potential to act as a drug target.
Pneumonitis in immunotherapy alone vs. chemoimmunotherapy: A systematic review and meta-analysis.
Authors: Barbaro Alexander Michael , Siskin Matthew , Grello Cassandra , Hernandez Adrian V , Dublin Jared , Breslin Sean , Punekar Salman Rafi , Velcheti Vamsidhar 
Published: June 2022

e21120 Background: Immune checkpoint inhibitors (ICIs) are commonly used in the treatment of non-small cell lung cancer (NSCLC), and are given alone or in combination with cytotoxic chemotherapy. These agents are sometimes associated with immune related adverse events (irAEs). Pneumonitis in particular is a common and sometimes life-threatening complication of treatment with ICIs, especially in lung cancer patients. Chemotherapy is known to cause immune suppression and deplete T cell populations, and might be expected to attenuate the incidence or severity of irAEs when given with ICIs. To date, few studies explore this possibility. This meta-analysis compared the incidence of any grade and severe (grade ≥3) pneumonitis in patients who received ICIs alone vs. combination ICI + chemotherapy for the treatment of advanced NSCLC. Methods: Embase and PubMed databases were searched through May 2021 for clinical trials investigating the use of ICIs for treatment of advanced NSCLC alone and/or in combination with chemotherapy. Interventions were categorized into ICI alone vs. ICI + chemotherapy and rates of any grade and severe (grade ≥3) pneumonitis for patients in each category were collected. The incidence of these events across interventions was aggregated using inverse variance weighting, and rates among patients who received ICI alone and ICI + chemotherapy were compared. Results: 1929 studies were identified by the initial search, of which 36 met inclusion criteria. From these, 24 interventional arms using ICIs alone (total patients n = 11,163) and 12 using combination therapy (n = 4,129) were identified and analyzed. ICIs included agents targeting PD1 (n = 22), PD-L1 (n = 11), CTLA-4 (n = 1), and the combination of CTLA-4 with PD1 or PD-L1 (n = 2). Rates of any grade pneumonitis did not differ significantly between patients who received ICI alone vs combination therapy (0.03; 95% CI 0.02-0.04 vs 0.04; 95% CI 0.02-0.08; P = 0.5). Rates of severe pneumonitis also did not differ between groups (0.01; 95% CI 0.01-0.02 vs 0.01; 95% CI 0.00 – 0.02; P = 0.5). Conclusions: No difference was found in the rates of any grade or severe pneumonitis between patients who received ICI alone vs. ICI + chemotherapy.
A phase 1 study in patients with advanced non-small cell lung cancer treated with stereotactic radiotherapy to the primary tumor combined with durvalumab and tremelimumab.
Authors: Kievit Hanneke , Muntinghe-Wagenaar M Benthe , Ubbels Fred , Wijsman Robin , Hijmering-Kappelle Lucie , Hiddinga Birgitta , Groen Harry J.M. , Kerstjens Huib A.M. , van der Wekken Anthonie J. , Hiltermann T.Jeroen Jeroen Nicolaas 
Published: June 2022

e21121 Background: Cancers can be recognized by the immune system and immunotherapy (ICI) has become an important treatment for lung cancer. Compared to chemotherapy, combining an anti-CTLA-4 and PD-L1 inhibitor increases response- and survival rates independent of PD-L1 status. We hypothesized that adding stereotactic radiotherapy (SBRT) to increase the release of cancer cell antigens might improve treatment results even further. Because of accumulating tumor heterogeneity it may be important to irradiate the primary tumor (addressing trunk mutations), rather than its metastases (branch mutations). We assessed toxicity of adding SBRT to (dual) ICI. Methods: In 3 sequential cohorts, ICI regimes combined with SBRT were studied in stage IIIB/IV NSCLC patients progressing on chemotherapy. All patients were irradiated on an FDG avid part of the primary tumor (1x20 Gy on 9cc) 1 week after the 1st dose of ICI; in case of dual ICI the 1st dose of the 2nd ICI was administered within 1 week following SBRT. Following treatments both ICI were combined. The 1st cohort (n = 3) received durvalumab (D) monotherapy for up to 1 year. The 2nd cohort starting with tremelimumab (T) and the 3rd cohort starting with D (both n = 6) received a combination of D and T (4 cycles) followed by D monotherapy for up to 1 year. The 2nd and 3rd cohort only proceeded when dose limiting toxicities (DLT) occurred in ≤33% of cases in the previous cohort. DLT was defined as any grade ≥3 toxicity that occurred during the first 8 weeks of therapy. Treatment related adverse events (TRAEs) were categorized using NCI CTCAE version 4.3. Descriptive statistics were used to summarize baseline characteristics and TRAEs. Results: Fifteen patients were included from June 2018 to November 2020. Last study visit was in September 2021. Baseline characteristics of the groups were comparable. The median irradiated tumor volume was 9.13 cc (8.98-9.60 cc) with a mean lung dose of 0.44 Gy (0.14-0.73 Gy). The V20 was nihil (0-0.1%) and the V5 1.8% (0-4%). There was 1 DLT in cohort 3 (colitis grade 3). There was 1 low grade TRAE (pneumonitis grade 2) in cohort 1. In cohort 2, 6 low grade TRAEs (CTC 1-2) were observed and 2 high grade (CTC 3) in 1 patient, who discontinued treatment. In cohort 3, 4 low grade and 1 high grade TRAE occurred. Median progression free survival was 2 months, median overall survival 10 months. Conclusions: No additional toxicity was observed by adding SBRT to the primary tumor to (dual) ICI. Clinical trial information: 2017-002797-39. [Table: see text]
Machine learning modeling of real-world primary resistance and hyperprogression in immune checkpoint inhibitor (ICI) treated advanced non-small cell lung cancer (aNSCLC) patients.
Authors: Das Rahul K , Hathi Deep K 
Published: June 2022

e21127 Background: Many ICI-eligible patients display primary resistance (10-res), with some experiencing hyperprogressive disease (HPD). Machine learning (ML) on real-world data (RWD) can improve our clinical and mechanistic understanding related to ICI response. Methods: XGBoost models were built on ConcertAI’s oncology clinicogenomic database, comprising structured EMR, curated records from unstructured documents, and NGS reports, to predict 10-res and HPD in aNSCLC patients treated with ICI or chemotherapy (CT) within their 1st three lines between January 2015 and June 2021. HPD was defined as either tumor progression, treatment (Tx) discontinuation, or death within 49 days from Tx start (index date). 10-res was defined as any of these events after 49 days but within 180 days from Tx start. Models were trained on a clinical (N = 7647, ICI = 3265, 10-res = 3909, HPD = 2076), and a clinicogenomic (CG) (2304, 1271, 1084, 596) cohort. A 60:20:20 split was used for training, validation, and testing. Baseline period was defined as 180 days prior to the index date. Prognostic and predictive factors were identified from Shapley Additive Explanation (SHAP) values. Results: The clinical model was superior at predicting HPD; the CG model was better at predicting 10-res (AUROC = 0.67 for both). Total metastases (≥ 2) and lower levels of hemoglobin (HGB), and lymphocytes, higher ALP were risk factors for both HPD and 10-res. Elevated WBC and bilirubin, higher heart rate, lower body temperature, and history of anti-inflammatory medications were risk factors for HPD. Non-ICI-based regimens, low TMB, lower PD-L1 expression, and mutations in EGFR or KEAP1 were risk factors for 10-res. Mutation in KRAS was protective of 10-res. In addition to PD-L1 and TMB, the models identified prior lung radiation, smokers, higher baseline comorbidities, and positive MMR status as predictive of lower risk of 10-res from ICI but not in CT. STK11 mutation was predictive of higher risk of 10-res from ICI vs. CT. Non-adenocarcinoma histology was predictive of higher risk of HPD from ICI vs. CT. Conclusions: ML on RWD generated evidence to support both established and emerging prognostic and predictive markers for ICI response.[Table: see text]
Mutational profile, clinical characterization, and outcomes of lung cancer in solid organ transplant recipients.
Authors: Li Shenduo , Manochakian Rami , Zhao Yujie , Lou Yanyan 
Published: June 2022

e21131 Background: Solid organ transplant recipients have increased risk for malignancies. Lung cancer is the second most common malignancy in this population. Those patients are usually on long-term immunosuppressive medications that may affect tumorigenesis, cancer characteristics, and treatment response. Previous studies have investigated the characteristics and outcomes of post-transplant patients with lung cancer in small-sized cohorts. However, the tumor mutational profile and detailed treatment response at different stages have not been reported. Methods: We conducted a retrospective study from a cohort of 52 solid organ transplant recipients who were diagnosed with lung cancer at Mayo Clinic from 2018 to 2021. We examined tumor molecular alteration using next generation sequencing (NGS), analyzed the treatment modalities, progression-free survival (PFS), and overall survival (OS) and compared those to the general population with lung cancer using historical data in previous large trials. Results: In our study, most transplanted solid organs are kidney (N = 28, 53.8%), followed by liver (N = 12, 23.1%) and heart (N = 9, 17.3%). The adenocarcinoma (N = 28, 53.8%) represented the most common histology, followed by squamous cell carcinoma (N = 19, 36.5%). It consisted of Stage I (30.8%), stage II (15.4%), stage III (25%), and stage IV (26.9%). The most common site of metastasis is bone (64.3%). Transplant recipients with lung cancer have a significantly high frequency of somatic BRCA 1/2 mutations (30.4%), compared to the general population with advanced lung cancer (2.1%, p < 0.001). The frequencies of TP53 mutations (52.2%) and EGFR mutations (30.4%) are also increased. For stage I patients who received surgery or radiation therapy, the disease-free survival (DFS) is 16.5 months. 9 of 14 stage IV patients received chemotherapy. The median number of cycles received is 4. The median PFS is 4.9 months, and the median OS of all stage IV patients is 6.1 months. 4 patients were found to have actionable EGFR mutations, and 3 of them were initially diagnosed with stage IIIA and received Osimertinib after progression. One stage IV patient who was post-liver transplant received pembrolizumab for up to 5 cycles before he developed aspiration pneumonia and then pursued hospice. The PFS is 3.7 months. No immune-related adverse event was reported. Conclusions: In our cohort of solid organ transplant recipients who developed lung cancer, we observed a much higher frequency of somatic BRCA 1/2 mutations, compared to the general population with lung cancer. In addition, our data suggested post-transplant patients with stage I lung cancer have a shorter disease-free survival, and patients with stage IV lung cancer have a shorter overall survival, compared to the general population with lung cancer. Further study containing a high number of solid transplant patients to validate these findings is warranted.