bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome analysis of immunotherapy and possible prognostic role of pretreatment neutrophil-lymphocyte ratio in lung cancer: An Appalachian study.
Authors: Yadala Vivek , Kachynski Yury , Tahboub Ihab , Titus Abraham , Khatri Jai Kumar , Vemula Bhavana , Urella Madhulika , Marshall Kelsey , Shenouda Mina , Jamil Muhammad Omer , Tirona Maria Tria 
Published: June 2023

e21053 Background: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of lung cancer resulting in better survival benefits. We are reporting outcome analysis of lung cancer patients treated with ICI in our institution. Methods: We performed retrospective chart review of lung cancer patients treated with ICI at our institution between June 2016 and March 2022. Results: A total of 289 patients were identified- 241 had non-small cell lung cancer (NSCLC) and 48 had small cell lung cancer (SCLC). A total of 109 patients (37.7%) developed immunotherapy related adverse events (IRAE): 92 (38.1%) with NSCLC and 17 (35.4%) with SCLC. Average time to develop IRAE was 3 months in both NSCLC and SCLC. IRAE grades 1,2,3,4 were noted in 33%, 20%, 15%, 31% patients respectively. 34 of 63 (53%) patients who received Ipilimumab-Nivolumab developed more IRAE than any other ICI with fatigue and dermatitis being the most common IRAE associated with this ICI. 79 of 183 (43%) patients who received RT developed IRAE (p = 0.012). Median overall survival (OS) for NSCLC was 35 months, 41 months, 27 months, 15 months for stages 1,2,3,4, respectively (p = 0.03). Median OS for extensive stage SCLC was 14.6 months. Median OS for NSCLC with and without IRAE was 30 and 23 months, respectively (p = 0.02). Median OS for SCLC with and without IRAE was 16.7 and 16.2 months, respectively (p = 0.5). Median OS for NSCLC when steroids were used to treat IRAE was 25 months, and 63 months if no steroids were used (p = 0.027). Better median overall survival rate was noted in patients with low Neutrophil-Lymphocyte ratio (defined as NLR < 5) 29.23 months vs 20.59 months (high NLR) (p = 0.019). Although demographics like male sex, smoking history, higher BMI and poor ECOG performance status had numerically increased the risk of developing IRAE, no statistical significance was noted. Conclusions: Overall results of our analysis are mostly consistent with the current literature on survival rates in Lung Cancer. IRAE may have a predictive role in survival, as we observed that patients with NSCLC developing IRAE had better survival rates. Ipilimumab-Nivolumab combination resulted in more IRAE than any other ICI. Pneumonitis was the most common IRAE among all patients receiving ICI. Also, Radiation-therapy increased the risk of developing IRAE. Our observation that steroid use in treating IRAE was associated with lower survival is concerning. This may be due to higher grade IRAE/toxicities and possible decreased ICI effectiveness. Regardless of IRAE, low pretreatment NLR resulted in better survival rates. The role of pretreatment NLR as a potential prognostic tool to assess survival outcomes requires validation in a randomized clinical trial.
Treatment outcomes in patients (pts) with advanced/metastatic non-small cell lung cancer (NSCLC) harboring MET amplification as a secondary oncogenic driver.
Authors: Ryder Alex , Oksen Dina , Boutmy Emmanuelle , Ellers-Lenz Barbara , Stroh Christopher , Karachaliou Niki 
Published: June 2023

e21056 Background: There is limited published evidence on the treatment outcomes of pts with oncogene driven NSCLC who have developed resistance to targeted therapies or novel therapies such as immune checkpoint inhibitors (ICIs) and have MET amplification ( METamp). METamp has been identified as a secondary driver of EGFR TKI resistance. We report here on real-world (rw) outcomes for these pts. Methods: A non-interventional, descriptive cohort study design was applied using ConcertAI electronic medical record data derived from US community oncology centers and linked with ASCO/CancerLinQ data. Eligible pts had stage IIIB–IV NSCLC, and METamp. Study period: Jan 1, 2004 – Oct 31, 2021. Subgroup analyses included 1: pts with oncogene driven NSCLC who received targeted therapy or ICIs after diagnosis of advanced NSCLC, then progressed and had a positive test for METamp, and 2: pts from subgroup 1 who received an EGFR TKI after diagnosis of advanced NSCLC, then progressed and had a positive test for METamp. The presence of METamp after progression on a therapy was hypothesized to indicate METamp as a secondary driver of resistance. Outcomes were analyzed for pts who received a subsequent line of systemic therapy after progression. Results: Of 8,454 pts with lung cancer and minimum 1 molecular test including MET alterations, 164 had METamp (1.9%) and were included in the study cohort. In subgroup 1, 35 pts had METamp detected (21.3%) after disease progression on a targeted therapy or ICIs (EGFR TKI n = 17, ICIs n = 11, other n = 7). Of those pts, 27 received a subsequent systemic therapy after disease progression. The rw overall response rate (ORR) was 18.5% (95% CI: 6.3, 38.1), the median rw progression-free survival (PFS) was 2.2 months (95% CI: 1.6, 4.2) and the median overall survival (OS) from start of the subsequent therapy was 11.3 months (95% CI: 3.4, 21.3). In subgroup 2, 17 pts had METamp detected after disease progression on an EGFR TKI (erlotinib or afatinib n = 13, osimertinib n = 4). Of those pts, 15 received a subsequent systemic therapy after disease progression. The rw-ORR was 13.3% (95% CI: 1.7, 40.5), median rw-PFS was 2.1 months (95% CI: 1.1, 4.6), and median OS from start of the subsequent therapy was 8.5 months (95% CI: 1.7, 15.2). Conclusions: METamp as a secondary driver of resistance is a new target for systemic therapy in pts with EGFR-mutant NSCLC who have developed resistance to EGFR TKIs. Overcoming this resistance using combinations with MET inhibitors is currently under investigation in several clinical trials. The analyses reported here suggests that the treatments available and current standard of care result in poor outcome for pts with METamp, highlighting the high medical unmet need in this population.
Biomarker testing and treatment patterns in US patients (pts) with advanced/metastatic non-small cell lung cancer (NSCLC) harboring MET amplification.
Authors: Ryder Alex , Oksen Dina , Boutmy Emmanuelle , Wang Yuexi , Nisbett Alnecia R. , Stroh Christopher , Johne Andreas 
Published: June 2023

e21057 Background: Limited published evidence exists on pts with advanced stage NSCLC harboring MET amplification ( METamp), a rare oncogenic driver. We report here real-world biomarker testing and treatment patterns for these patients. Methods: This was a non-interventional, descriptive cohort study using ConcertAI electronic medical record data derived from US community oncology centers and linked with ASCO/CancerLinQ data. Eligible pts had stage IIIB–IV NSCLC and METamp. Study period: Jan 1, 2004 – Oct 31, 2021. Results: Of 8,454 lung cancer pts with minimum 1 molecular test including MET, 164 had METamp (1.9%). Pts were mainly identified from 2015 onwards and primarily in oncology in the Southern and Midwest regions (86.6%). Majority of pts were tested by tissue biopsy (67.1%), 20.7% by liquid biopsy and 12.2% not specified. At least 64.5% of pts were highly MET amplified (either gene copy number ≥8 or by liquid biopsy ++, +++). Other mutations screened for were ALK, ROS1 and EGFR (99.4%, 98.2% and 97.6%), with oncogenic ALK, ROS1 fusions and activating EGFR mutations in 0.6% and 13.1%, respectively. BRAF and KRAS were less frequently screened for (90.2% and 87.2%), with potential oncogenic alterations in 2.0% and 12.6%. Of 127 pts tested for PD-L1 (by immunohistochemistry), 63.0% were positive, and 72.5% had tumor proportion score ≥50. Eighteen pts had METamp detected after receiving an EGFR tyrosine kinase inhibitor (TKI), indicating METamp as a secondary oncogenic driver. RB1 loss and MYC amplification, as potential mechanisms of MET inhibition resistance, were not frequently screened for (30.5% and 46.3%). RB1 loss was identified in 2.0% and MYC amplification in 15.8%. Next generation sequencing was the most frequent diagnostic used overall. A total of 144 pts (87.8% of 164 pts) received first-line (1L) anticancer therapy; platinum-based chemotherapy 57/144 (39.6%), immune-checkpoint inhibitors 50/144 (34.7%) or EGFR TKI monotherapy 24/144 (16.7%), other 2/144 (1.4%) and MET TKIs (mainly crizotinib) were used in 11/144 pts (7.6%) in 1L, 14/78 (17.9) in second line and 7/42 (16.7%) in third line. Conclusions: In this cohort of pts identified in a US community oncology setting, biomarker screening even for rarer genetic alterations occurred. Concomitant genetic alterations to METamp were infrequent except for alterations of EGFR and KRAS. The frequency of pts with high level of METamp in the cohort may explain the lower frequency of other biomarkers, as high level of amplification indicates a cleaner MET profile. Overall MET inhibitor treatment was not common. Screening for novel and rare biomarkers such as METamp as a primary or secondary oncogenic driver is becoming increasingly important to enable efficacious targeted treatment.
Therapeutic effects of combination with EGFR-TKIs and radiotherapy on the prognosis of stage IV lung adenocarcinomas harboring 19-Del or 21-L858R: A retrospective study.
Authors: Liang Shuai , Li Chengming , Zhang Yingyun , Hua Dong 
Published: June 2023

e21067 Background: To evaluate the therapeutic effects of combining epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) with radiotherapy on the prognosis of patients with stage IV lung adenocarcinomas (LUAD) that harbor either exon 19 deletion (19-Del) or exon 21 L858R mutation (21-L858R). Methods: Clinical data in the real-world study were retrospectively collected and analyzed from 177 stage IV LUAD patients who received the combination of EGFR-TKIs and radiotherapy at Shandong Cancer Hospital between June 2012 and August 2017. And the primary endpoint of the study was overall survival (OS). Results: The results revealed that the stage IV LUAD patients harboring 19-Del showed similar clinical characteristics as those harboring 21-L858R (all P > 0.05). The median OS (mOS) of all patients was 32.0 (95%CI, 28.6-35.5) months. Multivariate analysis identified EFGR mutations and thoracic radiotherapy as the independent factors in predicting OS ( P = 0.001, 0.013, respectively). Moreover, subgroup analysis showed that patients who received EGFR-TKIs plus bone metastasis radiotherapy or thoracic radiotherapy showed a longer OS in 19-Del group than those in 21-L858R group (mOS, 34.7 vs. 25.1 months, 51.0 vs. 29.6 months; P = 0.0056, 0.0013, respectively), while not observed for patients with brain metastasis radiotherapy (mOS, 34.7 vs. 25.1 months; P = 0.088). Conclusions: Although there were no significant differences in clinical characteristics of stage IV LUAD patients between 19-Del group and 21-L858R group, patients harboring 19-Del could still achieve longer OS than those harboring 21-L858R after receiving EGFR-TKIs in combination with radiotherapy.
Predicting non-small cell lung cancer response to immune checkpoint inhibitors with machine learning based on heterogeneous biomarkers.
Authors: Schmutz Hugo , Mattei Pierre-Alexandre , Tricarico Pierre , Contu Sara , Hugonnet Florent , Guisier Florian , Decazes Pierre , Chardin David , Humbert Olivier 
Published: June 2023

e21068 Background: In patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICPI), individual clinical, biological, and imaging prognostic biomarkers have recently been identified. However, the combination of these biomarkers has not yet been studied. This study aims to analyse various clinical, biological and 18FDG PET/CT parameters using machine-learning algorithms to build more accurate prognostic models of NSCLC response to ICPI. Methods: The exploratory cohort consisted of patients with metastatic NSCLC, treated with either pembrolizumab or nivolumab in monotherapy, included in two prospective cohort studies of our institution. For all patients, a total of 28 baseline quantitative features were collected just before the initiation of ICPI (12 clinical, 6 biological and 10 PET/CT parameters), such as the patient’s ECOG performance status, PD-L1 tumour expression level (PD-L1%), neutrophil to lymphocyte blood ratio, number and metabolism of lesions, metabolic tumour volume (MTV). The two endpoints were the progression-free survival at 6 months (6M-PFS) and the overall survival at 12 months (12M-OS). The 28 features were sorted according to their selection frequency by a LASSO logistic regression on extensive cross-validation to predict 6M-PFS and 12M-OS. The top eight features were selected using the intersection of the most frequently selected features of both outcomes and used to build a logistic regression to predict 6M-PFS and 12M-OS. An independent validation cohort was collected to assess the performance of the 8-features model. This cohort consisted of metastatic NSCLC patients treated with monotherapy ICPI and retrospectively included in three different hospitals: Nice (N =16), Monaco (N =10) and Rouen (N =19). We reported the area under the receiver operating characteristic (AUROC). Results: 117 patients were included in the exploratory cohort (N = 93 for training and features selection and N = 24 for the test set). Without any feature selection, the AUROC of the logistic regression was 73.6% and 77.6% on the test set. Using LASSO, the top eight selected features were: age, MTV, number of lesions, PD-L1%, smoking status, ECOG, SUVmax of the most intense lesion and blood sugar level. The AUROC of the 8-features model was 74.3% for 6M-PFS and 85.5% for 12M-OS on the test set. 45 patients were retrospectively included in the validation cohort. The AUROC of the model were 81.9% for the 6M-FPS and 88.2% for the 12M-OS. Conclusions: The combination of heterogeneous biomarkers provides a powerful model for predicting the outcomes of NSCLC patients treated with ICPI. Rigorous feature selection is a critical point in ML approaches to avoid overfitting. [Table: see text]
Safety and efficacy of stereotactic body radiotherapy (SBRT) to oligoresidual sites combine with osimertinib in stage IV EGFR mutant NSCLC patients: A prospective pilot study.
Authors: Chen Cheng , Wang Ying , Liao Siqin , Zheng Bin , Chen Chen , Zeng Bangwei , Liao Lianming , Xu Benhua , Chen Chun 
Published: June 2023

e21069 Background: Presently osimertinib is used as first-line therapy in stage IV EGFR mutation NSCLC patients. Unfortunately, acquired resistance gradually develops, resulting in disease progression in most patients after 1 to 2 years. A retrospective study demonstrates that similar to the first- and second-generation EGFR-TKIs, half of the patients experienced failure within the residual disease. Consolidative local therapy had been evaluated as a promising strategy to improve PFS and delayed the appearance of new metastatic lesions in the pre-osimertinib era. It is intriguing to hypothesize that new distant metastases may arise from drug-resistant tumor cells at the residual tumor lesions. Therefore, compared to the salvage SBRT, preemptive consolidative SBRT to all oligo-residual tumor sites could potentially prevent recurrence and improve survival. Of note, this proposal is challenging because both EGFR-TKI and thoracic radiation have a detrimental effect on pulmonary interstitial tissue. Two retrospective studies had reported severe pneumonitis with radiotherapy plus osimertinib. Therefore, the potential toxicity profile needs to evaluate prospectively. Therefore, we performed this preliminary trial (ChiCTR2100053807) to evaluate the safety of consolidation SBRT at maximal osimertinib response. Methods: Patients were enrolled if residual metastasis was limited to five sites. Consolidative SBRT was initiated to all residual sites with different doses (30–50Gy) and fractions (3-10) when maximal tumor shrinkage was achieved with osimertinib. The primary endpoint was an adverse reaction defined by the Common Terminology Criteria for Adverse Events, version 4.0. Results: 5 consecutive patients were enrolled between December 2021 and December 2022. 80% of their residual disease was located in the lungs and lymph nodes, which constituted targets for thoracic SBRT. The median time to maximal response was 3 months (range, 2-6). The median follow-up time from consolidative SBRT was 6 months（range,6-12）. The most common grade 1-2 adverse events included leukopenia (60%, n = 3), anorexia (40%, n = 2), lymphopenia (40%, n = 2), paronychia (40%, n = 2), rash (40%, n = 2), which were thought to be likely related to osimertinib. One patient suffered from grade 1 pulmonary fibrosis at 16 months after SBRT. There was no Grade 3/4 acute and late radiation toxicity. So far, no disease progression occur with a median follow-up time of 18 months（range, 13-19）. Conclusions: This pilot studydemonstrated concurrent treatment with osimertinib and SBRT for the oligo-residue disease at TKI maximum response was well tolerated. Future prospective, randomized studies are desirable to confirm these preliminary findings. Clinical trial information: ChiCTR2100053807 .
Anaplastic lymphoma kinase (ALK) and ROS 1– positive advanced NSCLC: A real-world institutional experience.
Authors: Bala Stalin Chowdary , G Sindhu , Chennamaneni Rachana , Konatam Meher Lakshmi , Gundeti Sadashivudu 
Published: June 2023

e21074 Background: A novel fusion gene of EML4-ALK and ROS 1 has been identified in a subset of non-small-cell lung cancers (NSCLCs). Patients with the ALK-EML4 and ROS1 fusion gene demonstrate unique clinicopathological characteristics and treatment with targeted therapy led to improved survivals. Various clinical trials had shown the efficacy of ALK inhibitors, and they had become the standard of care. The real-world data of ALK inhibitors from a developing country like India is sparse and the present study was designed to analyze the incidence and outcomes of ALK positive NSCLC. Methods: Data of advanced NSCLC patients diagnosed between 2016 and 2022 with ALK and ROS1 positivity was analyzed. Detection of ALK was done by IHC or fluorescent in situ hybridization (FISH) and ROS1 was done by FISH. Results: A total of 776 advanced NSCLC patients between 2016 and 2022 were tested for ALK of which 63(8.1%) were positive. The median age at presentation was 50 years (range, 19-80 years). Of 63 patients, 34(54%) and 29(46%) were males and females. Cough (83%) was the most common symptom at presentation followed by breathlessness (73%), anorexia (59%) weight loss (59%) and chest pain (43%). The median duration of symptoms was 3 months (range, 1-18). 44(86%) patients were never smokers and 9(14%) patients had history of smoking or tobacco usage. The most common site of metastases was opposite lung (59%) followed by bone (50%), pleural effusion (41%) and brain metastasis were seen in 13(21%) patients. Adenocarcinoma was the most common histology (95%). Detection of ALK positivity was done by IHC and FISH in 45(72%) and 18(28%) patients. Of 63 patients, 52 patients received at least 4 months of treatment and were assessed for survival. First line therapy was crizotinib, chemotherapy followed by maintenance crizotinib, ceritinib, Alectinib in 40(77%), 4(7.7%), 6(11.5%) and 2(3.8%) patients respectively. At a median follow up of 14 months, the one-year progression free and overall survival was 71% and 75% respectively. The 2 year and 3-year OS were 54% and 30% respectively. Of 322 patients tested for ROS1, 9(2.8%) were positive for ROS1 translocation and received first line therapy with crizotinib. The one-year PFS and OS of ROS 1 positive patients were 75% and 89% respectively. Conclusions: ALK and ROS1 positivity was seen in 8.1% and 2.8% of advanced NSCLC patients. Majority of patients were never smokers. Opposite lung and bone were the most common site of metastases. Approximately more than half of the patients had two-year survival rate and survivals are almost similar to clinical trials. Crizotinib is well tolerated in majority of patients.
Clinical efficacy analysis of furmonertinib and structural insights into sensitivity to diverse TKIs for NSCLC with EGFR exon 20 insertion.
Authors: Zhang Xiao , Feng Guoxing , Liu Baoxing , Han Huan , Dong Bosheng , Yang Yanfang , Zhu Hui , Wang Huijuan , Fan Saijun , Tang Hong 
Published: June 2023

e21084 Background: Currently approved EGFR TKIs have dissatisfactory efficacy in most advanced NSCLC with EGFR exon 20 insertion mutations (EGFRex20ins). Whereas，preclinical studies have shown that furmonertinib demonstrated significantly antitumor activity in NSCLC with EGFRex20ins in vitro and in vivo. Here, we analyzed the clinical efficacy of furmonertinib in patients(pts) who harboring EGFRex20ins and explored mechanism. Methods: A retrospective single-arm analysis was performed to evaluate the efficacy of 20 NSCLC pts harboring EGFRex20ins receiving furmonertinib treatment who were determined at three institutions between Feb 2021 to Jul 2022. ORR, DCR, PFS, DOR and OS were analysed. The last follow-up time was February 1, 2023. Meanwhile, we investigated the clinical efficacy of furmonertinib (8 pts) versus osimertinib (8 pts) as second-line treatment, because pts about furmonertinib as first-line treatment were immature. In addition, the binding activity of different EGFR TKIs to EGFRex20ins were computationally constructed based on the crystal structure of EGFR_D770_N771insNPG/V948R (PDB ID: 7LGS) by the Schrödinger software (2021-2 Release, Schrödinger Inc., Portland, Oregon). Results: There are 10 (50.0%) females and the median age was 51 (32-77) years old. Of the 20 pts selected, we found that EGFRex20ins p.S768_D770dup (n = 5) variants were more common. We observed 14 pts with PR and six pts with SD as best response to furmonertinib (ORR: 70.0%, DCR: 100%). All pts showed tumor shrinkage in target lesions (median best percent change, -36.43% [-74.78%, -5.56%]). Median PFS was 10.2 (95 % CI, 7.00-13.40) months(mo). Median DOR was 8.5 (95 % CI, 5.08-11.92) mo. 13 pts were still alive by the last follow-up date. Comparative analysis of the efficacy of different groups showed that median PFS was significantly longer in furmonertinib group than in osimertinib (10.2 vs 3.8 mo, p = 0.008). Median OS was numerically longer in furmonertinib group than in osimertinib (18.9 vs 11.7 mo, p = 0.148). No grade 3 or above adverse events were observed. Furthermore, rather than erlotinib (GlideScore: -5.564; MM/GBSA: -52.8044), gefitinib (-7.68; -47.317), and afatinib (-5.075; -44.64), furmonertinib (-11.085; -68.1575) and osimertinib (-10.031; -63.87) revealed favorable binding activity to EGFRex20ins, with furmonertinib being the most significant. Conclusions: Furmonertinib might have positive clinical efficacy to advanced NSCLC pts with EGFRex20ins on account of its favorable binding activity to EGFRex20ins. It may be the optimal choice for these pts in the future.