bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oligo-residual disease in PD-1/PD-L1 inhibitor-treated metastatic non-small cell lung cancer: Incidence, pattern of failure and clinical value of local consolidative therapy.
Authors: Zhang Jinmeng , Gao Jie , Jiang Shanshan , Zhou Yue , Guo Tiantian , Ni JianJiao , Zhu Zhengfei , Zhang Zhen 
Published: June 2023

e21143 Background: Growing numbers of clinical trials are testing the efficacy of incorporating local therapy into programmed death receptor (ligand) 1 (PD-1/PD-L1) inhibitors in metastatic non-small cell lung cancer (NSCLC), but the optimal timing and patient selection are still controversial. We aimed to examine the patterns of maximum tumor response and treatment failure in PD-1/PD-L1 inhibitor-treated NSCLC, and explore the potential clinical value of local consolidative therapy (LCT) in those with oligo-residual disease (ORD). Methods: Metastatic NSCLC treated with PD-1/PD-L1 inhibitors in three academic centers from May 2018 to December 2021 were retrospectively reviewed and those derived clinical benefit, defined as having objective response or durable stable disease lasting≥6months, were finally enrolled. Patterns of tumor response and treatment failure were extensively analyzed. ORD was defined as residual tumor distribution limited to 3 organs and 5 lesions, otherwise was defined as multiple residual disease (MRD). Local therapies targeting the residual tumor lesions performed after PD-1/PD-L1 inhibitors initiation and before initial disease progression, were considered as LCT. The primary endpoints were the overall survival (OS) and progression-free survival (PFS). Results: Of the 318 patients enrolled, ORD and MRD were documented in 122 (38.4%) and 196 (61.6%) patients, respectively. Those who developed ORD had a significantly longer OS than those with MRD (p = 0.006). The median time to best response was 4 months and more than 50% of the initial disease progression developed only from the residual tumor lesions, providing the preliminary rationale of LCT. Among the 122 patients with ORD, those receiving LCT (n = 39) had significantly longer PFS (p = 0.04) and OS (p < 0.001) than those without LCT. Moreover, LCT remained one of the independent predictors of improved PFS and OS after Cox analyses. Conclusions: Local consolidative therapy seems to be feasible and may provide extra survival benefit for metastatic NSCLC patients with oligo-residual disease after PD-1/PD-L1 inhibitor treatment.
Impact of next generation sequencing on a clinicians’ first line treatment decision in patients with stage IV non-small cell lung cancer.
Authors: Megahed Ahmed , Zheng Dominick , Chen Lie H. , Haque Reina , McGary Eric C 
Published: June 2023

e21160 Background: National Comprehensive Cancer Network (NCCN) guidelines strongly recommend biomarker testing for patients with advanced non-small cell lung cancer (NSCLC), specifically with broad, panel-based sequencing via NGS. Our study characterized how clinicians utilized NGS testing to make first line treatment decisions in patients with stage IV NSCLC. Methods: We conducted a cross-sectional study of members within an integrated healthcare system (Kaiser Permanente Southern California) diagnosed with stage IV NSCLC who completed NGS testing (Strata Oncology) between May 2019 to June 2021. Treatment start dates were used to divide patients into those who started treatment before and after NGS results, and those who did not receive treatment after NGS results. Patients harboring alterations in seven genes (EGFR, ALK, ROS-1, BRAF, KRAS, RET, and MET) were considered candidates for targeted first line therapy. Results: A sample of 760 patients with stage IV NSCLC completed NGS testing. The mean time from NGS order to result was 25 days. Of the 760 in the sample, 284 (37%) and 262 (34%) initiated treatment before and after NGS results were reported, respectively, while the remaining 214 (28%) did not receive any treatment up to 120 days after the NGS results were reported. 43% (323/760) of the sample was found to have a targetable mutation on NGS, of whom only 38% (124/323) initiated first line treatment with a targeted therapy. 56/124 (45%) were treated with targeted therapy prior to NGS results and 68/124 (55%) were treated with targeted therapy after NGS results. 61% (118/193) of EGFR, ALK, or ROS mutated patients started targeted therapy. 67/323 with a driver mutation did not receive any treatment and were referred to hospice. For those patients who initiated targeted therapy prior to NGS results, it suggests that clinicians ordered single gene testing in parallel with NGS, and that these results were available prior to NGS. Conclusions: NGS tests results were not exclusively used to inform first line treatment decisions in most patients with stage IV NSCLC, as most patients found to have a targetable mutation, were not treated with targeted therapy. Possible explanations include lengthy turnaround times for NGS testing and the availability of more timely single gene testing.
Prediction of brain metastases progression and overall survival in patients with metastatic non-small cell lung cancer treated by immune checkpoint inhibitors using a radiomic model.
Authors: Henon Clemence , Hendriks Lizza , Carré Alexandre , Mezquita Laura , Reuzé Sylvain , Ammari Samy , Aldea Mihaela , Robert Charlotte , Le Pechoux Cecile , Audigier-Valette Clarisse , Mazieres Julien , Lefebvre Corentin , Rabeau Audrey , Duchemann Boris , Botticella Angela , Planchard David , Deutsch Eric , Besse Benjamin , Sun Roger 
Published: June 2023

e21169 Background: Brain metastases (BMs) incidence is high in patients with metastatic non-small cell lung cancer (NSCLC). Immune Checkpoints Inhibitors (ICIs) are now standard of care for metastatic NSCLC in the first-line or beyond settings. However, less than half of patients will have a tumor response, and the determinants of BMs response to ICIs remain unknown. This study aims to evaluate the value of radiomics to predict control/progression of BMs at a lesion level, and outcomes at a patient level in the BM+ NSCLC population treated by ICIs. Methods: We conducted a retrospective multicenter (5 European centers) study including consecutive patients with NSCLC BMs and available baseline MRI before ICIs (evaluation cohort) or chemotherapy (control cohort) with a 2:1 ratio, between 2011 and 2021. After modified RANO (Response Assessment in Neuro-Oncology) assessment of individual BMs, we developed a radiomic model to predict BMs control/progression to ICIs at the first brain follow-up imaging. The ICIs cohort was split into two datasets used for (i) model training with 5-fold cross-validation and (ii) model testing. The Chemotherapy cohort was used to ensure the specificity of our model to ICIs-treated patients. Results: Ninety-four and 49 patients were included in the ICIs and Chemotherapy cohorts respectively, of which 56 (59.6%, N = 227 BMs) and 39 (79.6%, N = 192 BMs) patients had available brain follow-up imaging. The ICIs cohort was specifically enriched in radiomic features which were significantly associated to BMs progression. Our final model, based on extreme gradient boosting (xgboost) on BMs > 10mm from the training set (N = 39 BMs), could predict individual BMs progression to ICIs with an area under curve (AUC) of 0.77 (p-value = 0.029, 95% CI [0.56-0.98]) in the test set (N = 20 BMs). We further generated a radiomic score to stratify BM+ NSCLC ICIs-treated patients between High-Risk or Low-Risk groups according to the predicted individual BMs progression. High-risk patients were associated with worse overall survival (OS) (median OS of 6.3 months, 95% CI [3.02-10.49]) compared to Low-risk patients (median OS of 11.87 months, 95% CI [7.02-21.90], p = 0.042). The prognostic value of the radiomic score on OS was validated in a multivariate analysis in the ICIs cohort (Table). Conclusions: To our knowledge, this is the first study to explore the value of radiomics in the prediction of BMs response to immunotherapy. Prospective evaluation will confirm the generalizability of our model in clinical practice.[Table: see text]
Biomarkers to predict the efficacy of immune checkpoint inhibitors in patients with non-small-cell lung cancer with actionable genetic alterations.
Authors: Jun Soojin , Jung Hyun Ae , Ahn Myung-Ju , Ahn JinSeok , Lee Se-Hoon , Sun Jong Mu , Park Sehhoon , Cho Juhee 
Published: June 2023

e21175 Background: Although the efficacy of immune checkpoint inhibitors (ICI) in patients with actionable genetic alterations (AGAs) in non-small-cell lung cancer (NSCLC) has been known to be modest, some patients demonstrated improved survival. Thus, this study aimed to find predictive biomarkers for ICI in patients with NSCLC with various AGAs and to identify the predictive biomarkers for ICI efficacy. Methods: We compared the progression-free survival (PFS) of 324 advanced NSCLC patients who received ICI monotherapy (as over second-line therapy) by different AGAs from January 2018 and July 2022 at the Samsung Medical Center. To identify predictive markers of ICI, we adjusted the impacts on PFS of ICI in smoking status, PD-L1 expression, TP53, KEAP, STK11 mutation status, and steroid use during ICI monotherapy. Results: The median age was 63.1 years (range, 27.8–84.8) and 53.1% of patients was male, and 46.3% of patients was an ex-/or current smoker. A total of 324 patients were included with the following AGAs: EGFR mutation (n = 149, 46.0%), ALK rearrangement, (n = 12, 3.7%), KRAS mutation (n = 72, 22.2%), HER2 mutation or amplification (n = 34, 10.5%), and MET ex14 skipping or amplification (n = 32, 9.9%), ROS1 rearrangement (n = 9, 2.8%), BRAF V600E (n = 9, 2.8%), and RET rearrangement (n = 7, 2.2%). The median PFS was 2.0 months (95% confidence interval, 1.8–2.2) in the total AGA group. The 6-month PFS rate was 25.8% (19.5–34.3) in the group with KRAS/ BRAF V600E/ MET/ HER2 and 12.8% (8.6–19.1) in the group with EGFR/ ALK/ ROS1/ RET (P < 0.01). In the group with KRAS/ BRAF V600E/ MET/ HER2, KEAP, or STK11 wild-type (P = 0.03), PD-L1 (≥1%) (P < 0.01) and steroid use during ICI monotherapy due to immune-related adverse events (IRAE) (P < 0.01) were related to a favorable PFS of ICI; however, no statistical significance was found for TP53 mutation and smoking status for PFS of ICI. In the group with EGFR/ ALK/ ROS1/ RET, PD-L1(≥ 50%) was the only factor that was related to a favorable PFS, and not TP53 mutation status, KEAP, or STK11. Conclusions: This study showed a difference in PFS among each type of AGAs. Although there are limitations due to the small number of patients, the KRAS/ BRAF V600E/ MET/ HER2 group had a favorable PFS compared with the EGFR/ ALK/ ROS1/ RET group . KEAP/STK11/PD-L1 status and steroid use due to IRAE predicted favorable PFS of ICI in the KRAS/ BRAF V600E/ MET/ HER2 group .
Immune therapy related adverse events in metastatic non-small cell lung carcinoma patients at a rural academic center.
Authors: Pasli Melisa , Muzaffar Mahvish , Kannaiyan Radhamani 
Published: June 2023

e21203 Background: Immune checkpoint inhibitors (ICIs) have revolutionized treatment for stage IV non-small cell lung cancer (NSCLC) patients. Immune related adverse events (irAEs) are the diverse immunologic side effects of patients receiving ICIs and may result in significant patient morbidity, subsequently impacting quality of life. If severe enough, irAEs may lead to hospitalization and may necessitate administration of immunosuppressants or IL-6 receptor antagonists. Our study sought to characterize irAEs in a patient population receiving ICIs at a rural tertiary care center. Methods: This was an IRB-approved retrospective cohort study using SPSS version 28. Patients with stage IV NSCLC receiving ICIs at ECU Health Medical Center were analyzed and 190 patients met inclusion criteria. Results: Of our cohort, 66.3% (n = 126) experienced at least one irAE of any grade, 46.3% (n = 88) were hospitalized due to grade 3 or 4 irAE, 55.7%(n = 106) were either started on steroids or had a dose increase to treat the irAE, 48.9% (n = 93) received immunosuppression to treat the irAE, and 41.5% (n = 79) had immunotherapy held either temporarily or permanently due to the irAE. 25.7% (n = 49) were rechallenged and 18.9% (n = 36) experienced an irAE after being rechallenged. 34.7% (n = 66) experienced pneumonitis, 22.1%(n = 42) constitutional symptoms, 17.8%(n = 34) gastrointestinal, 10.5%(n = 20) neurological, 10.5%(n = 20) dermatological, 6.8%(n = 13) endocrine, 3.6%(n = 7) hematological, 3.1%(n = 6) musculoskeletal, and 3.1%(n = 6) cardiovascular irAEs. When adjusting for race, sex, line of therapy, and histological type, logistic regression analysis yielded no significant difference in the probability of developing an irAE when comparing patients treated with nivolumab versus atezolizumab and pembrolizumab. Patients treated with atezolizumab (OR:0.17; p = 0.020; 95% CI:0.039-0.757) and pembrolizumab (OR:0.20; p = 0.021; 95% CI:0.055-0.785) were less likely to be hospitalized for an irAE when compared to patients treated with nivolumab. When rechallenged, no difference was noted in recurrent irAE development when comparing pembrolizumab and nivolumab. Cox regression analysis demonstrated that patients treated with atezolizumab (OR:0.36; p = 0.010; 95% CI:0.167-0.781) and pembrolizumab (OR:0.29; p < 0.001; 95% CI:0.291-0.148) had better OS when compared to nivolumab. No difference was evident when comparing White and Black patients experiencing any grade irAE (n = 69, n = 53), grade 3 or 4 irAE (n = 44, n = 40), OS (n = 104, n = 80), and PFS (n = 104, n = 80). Conclusions: Our demonstrated irAE side effect profile is similar to those of published studies. No racial disparities were noted in our cohort when analyzing for any grade irAEs, grade 3 or 4 irAEs, OS, and PFS. Our study yields clinically pragmatic insight into better understanding how various factors, such as ICI selection and race, may impact patient outcomes.
Comparing survival and clinical characteristics of patients with non-small cell lung cancer who received immune checkpoint inhibitor therapy less than and more than 2 years.
Authors: Rose Brandon Edward , Edwards Kyle , Kareff Samuel A. , Ramos Leana , El-Abbar Nora , Lopes Gilberto , Rodriguez Estelamari 
Published: June 2023

e21214 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the management of non-small cell lung cancer (NSCLC). The current standard of care based on ICI trial design is to discontinue ICI treatment after 2 years, disease progression, or intolerance. The disease progression patterns and survival of patients treated with ICIs beyond 2 years have not been well described in real-world clinical settings. Methods: We retrospectively analyzed 689 patients with advanced NSCLC who received ICI treatment at the University of Miami between June 2004 and February 2020. Patients who survived ≥ 2 years after starting ICI were defined as long-term survivors (LTS) and were divided into two treatment groups: ICI < 2 years or ≥ 2 years. The primary outcome measured was overall survival (OS). The secondary outcomes were demographic, clinical, and pathologic characteristics. Results: A total of 689 patients with advanced NSCLC were administered immunotherapy. Amongst this group, 186 (27%) were designated as LTS, 53 (28%) were treated with ICI ≥ 2 years, and 133 (72%) were treated < 2 years. LTS who were treated for ≥ 2 years had a median OS of 77.4 months compared to 46.2 months for LTS who were treated for less than 2 years (p = 0.0045). The 3-year OS for the ≥ 2 year cohort was 85.9%, compared to 70.8% for the < 2 year cohort. The characteristics of the < 2 year and ≥ 2 year cohort are described in detail in Table 1. There were no statistically significant differences in median age, gender, race, ethnicity, tobacco use, histology, PD-L1 status, or BMI. Conclusions: In this real-world analysis, prolonged ICI therapy provided a long-term benefit with a 15.1% increase 3-year OS in LTS. Patients in both groups had similar demographic characteristics. PD-L1 expression was increased in the > 2 year group. Larger prospective trials are needed to reveal the potential benefits and toxicities of increased ICI treatment length in patients with advanced NSCLC. [Table: see text]
Hospitalization for immune related toxicity and overall survival (OS) among patients with metastatic non-small cell lung cancer (NSCLC) treated with first-line pembrolizumab.
Authors: Khorasanchi Adam , Zhao Songzhu , Wei Lai , Li Mingjia , Ho Kevin , Abu-Sbeih Hamzah , Alexander John Howard , Goodyear Evelyn , Secor Austin , Shields Peter G. , He Kai , Kaufman Jacob , Memmott Regan Michelle , Alahmadi Asrar , Carbone David Paul , Otterson Gregory Alan , Meara Alexa Simon , Presley Carolyn J , Owen Dwight Hall 
Published: June 2023

e21215 Background: Few studies have investigated the association between patients with NSCLC hospitalized due to complications of ICI and subsequent OS. Immune related adverse events (irAEs) are autoimmune syndromes, side effects of ICIs. We evaluated the rates of irAEs among patients with metastatic NSCLC hospitalized within 1 year of pembrolizumab treatment and OS. Methods: This retrospective study included 102 patients (out of 411 total patients screened) with Stage IV NSCLC treated with a first-line pembrolizumab regimen (alone or in combination with chemotherapy) at the Ohio State University from 2018-2022 who developed an irAE. A chart review was completed for patient demographics, unplanned hospitalizations (irAE or any reason) within 1 year of ICI, and type of irAEs leading to hospitalization. Descriptive statistics were summarized and compared by irAE hospitalizations (Yes vs No) or any reason hospitalizations (Yes vs No). Kaplan-Meier survival analysis and log-rank test were used to assess the associations between these two groups with OS. Results: Twenty-one percent (21/102) of patients were hospitalized for irAE within 1 year, for the following irAE types: 7 pneumonitis (33.3%), 6 colitis (28.6%), 2 dermatitis (9.5%), 1 hepatitis (4.8%), 1 myalgia (4.8%), 1 neurological (4.8%), and 1 hypophysitis (4.8%). 68 were hospitalized for any reason including irAE, infections, cancer progression, and pain. Patients age, gender, race, and body mass composition were similar between two groups. Patients with irAE hospitalization had shorter OS (13.8 m, 95% CI 2.73-NR) than those without irAE hospitalization (53.6 m, 95% CI 33.18-NR, p = 0.0105). Hospitalization irAE rates were not significantly different between pembrolizumab alone and pembrolizumab-chemotherapy, however overall hospitalization rate was higher in pembrolizumab-chemotherapy (77%) than pembrolizumab alone (55%), p = 0.0214. Conclusions: This study suggests patients who are hospitalized following ICI treatment may have worse outcomes. Hospitalization rates overall were higher for patients treated with pembrolizumab-chemotherapy than pembrolizumab alone. Further investigation is needed to confirm these findings as our study was limited to patients who experienced irAEs during treatment.
Ethnic disparities in biomarker testing and targeted therapy use in metastatic lung adenocarcinoma: A 2014-2021 analysis.
Authors: Pereslete Alyssa , Ozair Ahmad , Khosla Atulya Aman , Bellur Shreyas S , Hurmiz Charlie , Marada Suresh , McCracken Andrea , Watson Mark Layton , Ahluwalia Manmeet Singh ,   Guardian Research Network Collaborators
Published: June 2023

e21216 Background: Racial and ethnic disparities have been demonstrated to be widespread in lung cancer, including in the US. Despite insurance coverage for standard biomarker testing, testing rates remain low in minority populations. This work sought to analyze institutional data to assess whether there existed ethnic disparities in biomarker testing rates and receipt of targeted therapy between Hispanic/Latino and non-Hispanic/Latino patients of metastatic lung adenocarcinoma (mAdenoCa). Methods: A retrospective study was conducted and reported following ‘strengthening the reporting of observational studies in epidemiology’ (STROBE) guidelines. All Hispanic white and non-Hispanic white patients of mAdenoCa seen at our tertiary care institution in South Florida from 01/2014 to 12/2021 were identified and included through Guardian Research Network (GRN) platform. Socio-demographic, clinicopathological, and tumor molecular features along with treatment-related characteristics were analyzed via descriptive and comparative statistics. Results: A total of 268 mAdenoCa patients were included, of which 179 patients were Hispanic or Latino and 89 were not Hispanic or Latino. Biomarker testing data is reported in the table. Data of MET, KRASG12C, VKIRAS, and HER3 was not available in all cases. The unadjusted product-limit survival analysis indicated worse outcomes for Hispanic whites as compared to non-Hispanic counterparts. There were no differences found regarding targeted therapy use in either population. Conclusions: While metastatic lung adenocarcinoma patients at our center showed no differences in biomarker testing or targeted therapy use, the non-availability of data regarding several key mutations indicates a major dearth of testing. Future studies need to evaluate actionable strategies for improving the existing low testing rates in patients with mAdenoCa, particularly in racial and ethnic minorities. [Table: see text]
Patient characteristics and treatment patterns in BRAF-mutated unresectable or metastatic melanoma in the United States: A snapshot from real-world data.
Authors: Mesana Laura , Chen Kristina , Li Benjamin , Rezai Nana , Noshad Sina , Zhao Yajin , Abraham Anup 
Published: June 2023

e21506 Background: BRAF mutations are found in 40-60% of patients with unresectable/metastatic melanoma (m-melanoma). Recently, several new BRAF-targeted therapies (TT) have been approved, transforming the treatment landscape for patients with BRAF-mutated (BRAFm) unresectable/m-melanoma. This analysis aimed to describe patient characteristics and treatment patterns in BRAFm unresectable/m-melanoma patients receiving treatment during November 2015-June 2021. Methods: A retrospective analysis using Flatiron Health’s database was conducted. Adult patients with unresectable/m-melanoma who had evidence of the BRAF-V600 activating mutation were included. Patients were indexed at first-line (1L) therapy initiation. Treatments of interest were classified into immuno-oncology (IO) therapies and TT. All analyses were descriptive. Results: 671 unresectable/m-melanoma patients (average age: 62.7 years, 64.1% male) were included. Among them, 64.4% of patients received IO, 34.4% received TT, and 1.2% received IO+TT. In 1L, ipilimumab+nivolumab and dabrafenib+trametinib were the most common IO (50.9%) and TT (71.9%), respectively. The median duration of 1L was 8.0 months (9.7 months in IO and 6.7 months in TT). Among IO-treated patients, 28.5% had Eastern Cooperative Oncology Group (ECOG)≥1, 23.4% had elevated lactate dehydrogenase (LDH) levels, and 4.9% had 3+ metastases identified. Among TT-treated patients, 42.9% had ECOG≥1, 27.3% had elevated LDH, and 7.8% had 3+ metastases identified. Approximately one-third of the patients (n = 204) received their 1L treatment prior to being tested for BRAF mutation; the majority of whom (90.2%) received IO. 273 patients (40.7%) advanced to a second line (2L). In 2L, 14.3% of patients received the same class of therapy as in 1L, 44.7% switched from 1L IO to 2L TT, and 35.2% switched from 1L TT to 2L IO. In 2L, ipilimumab+nivolumab (50.0%) in IO and dabrafenib+trametinib (60.7%) in TT were the most common combinations. The median duration of 2L was 5.0 months (3.7 months in IO and 6.5 months in TT). Conclusions: Despite the recent availability of TT combinations for BRAFm unresectable/m-melanoma, IO is about twice as frequently prescribed than TT in 1L. One-third of the patients received treatment before BRAFm testing results were available and most of them were prescribed IO. These findings along with elevated ECOG scores, the proportion of 3+ metastases, and elevated LDH levels seen in TT patients, suggest TT is often offered to patients with a high disease burden in the current practice settings.