bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial disparities in the clinical use of durvalumab for patients with stage III unresectable non–small cell lung cancer treated at Veterans Health Administration facilities.
Authors: Moore Amanda , Nooruddin Zohra , Reveles Kelly R , Datta Paromita , Brannman Lance , Cotarla Ion , Frankart Andrew , Mulrooney Tiernan , Jones Xavier , Frei Christopher R 
Published: June 2022

8526 Background: Evidence from the PACIFIC study and real-world data highlight the benefit of durvalumab in patients with stage III unresectable non-small cell lung cancer (UR-NSCLC). However, limited literature exists regarding disparities in durvalumab treatment patterns such as treatment initiation delays (TID), treatment interruptions (TI), number of doses, duration of therapy (DOT), adverse effects (AEs), and treatment discontinuation (TD) in minority populations. Methods: Patients with stage III UR-NSCLC and a self-reported racial identity of Black or White treated with durvalumab following chemoradiotherapy (CRT) at any Veterans Health Administration (VHA) facility from January 1, 2017 to June 30, 2020 were included. Patients were followed from their date of durvalumab initiation through the earliest of their last VHA visit, loss to follow up, death, or end of the study; therefore, all patients had the opportunity to be treated for 12 months. Patients were excluded if durvalumab therapy was ongoing at the end of the study. Patient charts were retrospectively reviewed for baseline characteristics and durvalumab treatment patterns including TID (>42 days from end of CRT to durvalumab start), TI (>28 days between doses), number of doses, DOT, AEs, and TD. Nominal variables were compared using chi-square/Fisher’s exact tests. Continuous variables were compared using Student’s t-tests/Wilcoxon Rank Sum tests. Results: Among 924 patients, Black patients were younger than White patients (median age 67 years [IQR, 63-71] vs. 70 years [IQR, 65-73]; p<0.01), more likely to be current smokers (54% vs. 45%; p=0.03), with more chronic liver disease (22% vs. 9%; p<0.01), but less COPD (63% vs. 72%; p=0.01). Black patients experienced more TI (25% vs. 18%; p=0.03) but TID, number of doses, DOT, and TD were similar between the groups. Black patients were less likely to have an immune-related AE (irAE) (28% vs. 36%; p=0.03) (and less pneumonitis (7% vs. 14%; p<0.01)). Toxicity was the reason for TD in 12% of Black patients vs. 20% of White patients (p=0.01), with no other significant (α < 0.05) differences in reported reasons for TID, TI, or TD between the groups. Conclusions: In this real-world study, Black patients experienced similar TID, number of doses, and DOT as White patients. Black patients were less likely to experience an irAE (including pneumonitis) but experienced more TI; TD were similar but more likely to be from toxicity for White patients. Future research is needed to validate these findings.[Table: see text]
Pre-existing interstitial lung abnormalities are independent risk factors for interstitial lung disease during durvalumab treatment after chemoradiotherapy in patients with locally advanced non–small lung cancer.
Authors: Daido Wakako , Masuda Takeshi , Imano Nobuki , Matsumoto Naoko , Shoda Hiroyasu , Hamai Kosuke , Iwamoto Yasuo , Takayama Yusuke , Mishima Shohei , Masuda Ken , Kawase Shigeo , Awaya Yoshikazu , Nishimura Yoshifumi , Shiota Naoki , Ishikawa Nobuhisa , Yamasaki Masahiro , Kitaguchi Soichi , Fujitaka Kazunori , Nagata Yasushi , Hattori Noboru 
Published: June 2022

8528 Background: The standard treatment for locally advanced non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by treatment of durvalumab, one of immune checkpoint inhibitors (ICI). Interstitial lung disease (ILD) is a clinically life-threatening toxicity of CRT or durvalumab. The patient-characteristics or dose-volume histogram parameters of radiotherapy have been reported to be the risk factors for radiation-induced pneumonitis. However, the risk factors for ILD during durvalumab therapy has not been established. Interstitial lung abnormalities (ILA) are generated by aging or smoking, and manifest as minor interstitial shadow on lung computed tomography (CT). We previously reported that ILA were risk factors for ICI-induced ILD in patients with advanced NSCLC, as well as non-lung cancer. Therefore, we investigated whether ILA could be risk factors for ILD during the durvalumab therapy. Methods: We retrospectively enrolled NSCLC patients who received durvalumab after CRT at 10 institutions from July 2018 to June 2021. Patient-information, patient-characteristics, dose-volume histogram parameters, chest CT findings, and laboratory data, were obtained. CT findings were examined using CT obtained after CRT and prior to durvalumab therapy. Results: A total of 153 patients were enrolled, and the prevalence of ILA was 37.8% (56 patients) before durvalumab treatment. Among the enrolled patients, 94 (63.5%) developed ILD during durvalumab therapy. The proportion of patients with grade 1, grade 2, or grade 3 ILD was observed to be 29.7% (44 patients), 25.7% (38 patients), and 8% (12 patients), respectively. Univariate logistic regression analysis revealed that higher age, higher dose volume histogram parameters (V5, V20, mean lung dose), and the presence of ILA were significant risk factors for grade 2 or more ILD. Multivariate logistic regression analysis showed that ILA, especially ground grass attenuation in ILA, was an independent risk factor for grade 2 or more ILD (odds ratio: 7.02, 95% CI: 2.95-16.69, p < 0.0001). Conclusions: Pre-existing ILA are risk factors for ILD during durvalumab treatment after CRT. This observation is consistent with previously reported findings in patients with advanced lung cancer and non-lung cancer. Therefore, we should pay more attention to the development of grade 2 or more ILD during durvalumab treatment in patients with ILA.
Observer performance study to examine the feasibility of the AI-powered PD-L1 analyzer to assist pathologists’ assessment of PD-L1 expression using tumor proportion score in non–small cell lung cancer.
Authors: Kim Seokhwi , Kim Hyojin , Jung Wonkyung , Cho Soo Ick , Bentz Joel , Clingan Warren , Golden Kevin , Arcega Ramir , Bae Hyunsik , Butler Dawn L. , Choi Sangjoon , Farinola Maryam , Harrison Daniel , Hwang Soohyun , Jung Minsun , Kashikar Nilesh , Kim Hyunsung , Manny Julia , Winters Carmen , Hughes Jonathan H. 
Published: June 2022

8529 Background: Programmed death ligand 1 (PD-L1) expression is the standard biomarker for PD-L1 inhibitors in advanced non-small cell lung cancer (NSCLC). However, evaluation of PD-L1 tumor proportion score (TPS) by pathologists causes inter-observer variation and demands time to interpret. This study aimed to evaluate the benefit of the artificial intelligence (AI) algorithm in assisting pathologists to determine TPS on PD-L1 immunohistochemistry (IHC) whole-slide images (WSIs) in NSCLC. Methods: Lunit SCOPE PD-L1, an AI-powered PD-L1 TPS analyzer, was developed from 393,565 tumor cells annotated by board-certified pathologists for PD-L1 expression in 802 WSIs stained by 22C3 pharmDx IHC. The AI model was developed based on a region-based convolutional neural network, and the model can detect and count PD-L1 positive or negative tumor cells from WSIs to calculate TPS. Seven independent board-certified pathologists scored ground truth (GT) of PD-L1 TPS from 199 WSI of NSCLC stained by 22C3 pharmDx IHC. TPS from each GT reader was grouped as negative (< 1%), low (1% to 49%), or high (≥ 50%). The GT of each slide was determined by the consensus of GT readers. Another twelve independent board-certified pathologists scored PD-L1 TPS from the same WSIs as observer performance testers (OPT). They scored TPS twice with a washout interval of 4 weeks, with or without AI assistance. TPS accuracy change and reading time of OPT reader according to the presence or absence of AI assistance were analyzed. Results: The standalone accuracy of the AI model was 0.809 (95% CI: 0.690–0.941). With AI assistance, the overall accuracy of TPS had been changed from 0.799 (95% confidence interval [CI]: 0.764–0.836) to 0.832 (95% CI: 0.796–0.869) (P = 0.004). AI assistance increased the accuracy rate in 11 out of 12 OPT readers. The result of the generalized linear mixed model revealed that AI assistance and specimen type affected the probability of correct answer, while the order of reading did not (Table). The mean time to read with AI was 195.4±506.5 (mean±standard deviation) seconds, which was significantly shorter than the mean time to read without AI (285.1±1578.4, P <0.001). Conclusions: This study demonstrates that an AI-powered PD-L1 TPS analyzer can assist board-certified pathologists in evaluating TPS of NSCLC by improving the accuracy of TPS group evaluation and reducing the time to read slides.[Table: see text]
Equity for under-served populations in lung cancer screening and treatment: Does mobile low-dose CT scanning lead to stage shift and diagnosis with potential cures at 4 years of follow-up?
Authors: Raghavan Derek , Doege Darcy L. , Dungan Kia , Wheeler Mellisa S , Doty John , Hickman Glenn , Mileham Kathryn Finch , Carrizosa Daniel R. 
Published: June 2022

8551 Background: Randomized trials proved that screening high-risk patients with LDCT of chest reduces lung cancer mortality. Under-served patients have missed this benefit in most studies through access issues. We showed that mobile LDCT improves access and now assess if this translates to equity of survival. Methods: We used two coaches with BodyTom © portable 32 slice low-dose CT scanners (Samsung) to screen uninsured and under-served heavy smokers for lung cancer (Oncologist, 2019). All films were reviewed by central panel using LUNG RADS technique. Protocol was approved by Advarra IRB. Medicare pts were excluded as insurance covered them for LDCT (causing negative bias for diagnosis as the elderly are at high risk). Results: We initially screened 1200 uninsured/under-insured subjects, mean age 61 years (range 55-64), with average pack year history of 47.8 (30-150); 61% male; 18% Black, 3% Hispanic/Latino; 78% rural. We found 97 pts with LUNG RADS 4 (high risk) lesions, 30 lung cancers (2.5%), including 18 at stage I-III treated with curative intent (60%); 5 incidental non-lung cancers (renal CA 2, head & neck CA 1, pancreas CA 2); > 50% with intercurrent cardiovascular disease and COPD seen on LDCT. Of eligible first-screen subjects, 51% attended 12 month repeat LDCT and 27% attended third LDCT. One pt (6%) treated with curative intent has relapsed to date (median follow up 2.5 years, with 25% beyond 3 years). An additional 288 screened pts revealed 9 lung cancers (5 stage I-III), confirming shift to early stage disease at diagnosis. Conclusions: Mobile LDCT yields higher screening rate for under-served pts than prior hallmark trials, with shift to early-stage detection of lung cancer, with sustained treatment-induced remissions beyond 4 years. This approach could be applied to improve national lung cancer survival in the under-served.
Clinical activity of pembrolizumab monotherapy in diffuse malignant peritoneal mesothelioma.
Authors: Wang Xiao , Offin Michael , Roshkovan Leonid , Miura John , Ginsberg Michelle S. , Ciunci Christine Agnes , Egger Jacklynn V. , Walker Suzanne , Cercek Andrea , Litzky Leslie , Nash Garrett Michael , Haas Andrew , Karakousis Giorgos , Cengel Keith A. , Katz Sharyn I. , Zauderer Marjorie Glass , Langer Corey J. , Marmarelis Melina Elpi 
Published: June 2022

8557 Background: Among patients with malignant mesothelioma, pembrolizumab has demonstrated activity in diffuse pleural mesothelioma (DPM), with limited data available for those with diffuse malignant peritoneal mesothelioma (DMPM). DMPM represents a clinically distinct entity from DPM and disease specific outcomes data is needed. We present real world data on the efficacy of pembrolizumab in DMPM. Methods: In this retrospective study, we identified patients with DMPM treated with pembrolizumab at two tertiary care cancer centers between 1/1/2009 and 1/1/2021. Clinicopathologic features were annotated. Median progression free survival (mPFS) and median overall survival (mOS) were calculated using Kaplan-Meier curves. Best overall response rate (BOR) was determined using RECIST 1.1 criteria. Association of partial response with disease characteristics was evaluated using Fisher’s exact test. Results: We identified 24 patients with DMPM who received pembrolizumab (median age 62 years, 63% never smokers, 58% female, 75% had epithelioid histology). All patients received systemic chemotherapy prior to pembrolizumab (median prior lines of therapy: 3). BOR was 17% (3 partial responses, 10 stable disease, 5 progressive disease, 6 lost to follow-up). With a median follow up time of 29.2 months, mPFS was 4.9 months and mOS 20.9 months from pembrolizumab initiation. Three patients experienced PFS of > 2 years. Among the 14 patients who underwent next generation sequencing of tumor tissue, there were 8 somatic BAP1 alterations. Among the 17 patients tested for PDL1, 6 had positive PDL1 expression (1-80%). There was no association between partial response and presence of a BAP1 somatic alteration (p = 0.453), PDL1 positivity (p = 0.7) or non-epithelioid histology (p = 0.55). Conclusions: Pembrolizumab is active in a PDL1 unselected cohort of patients with DMPM. The overall response rate of 17% and mPFS of 4.9 months in this 75% epithelioid histology cohort warrants further investigation to identify those most likely to respond to immunotherapy, especially among epithelioid histology.
A phase 1/2 trial of lurbinectedin (L) in combination with pembrolizumab (P) in relapsed small cell lung cancer (SCLC): The LUPER study.
Authors: Calles Antonio , Navarro Alejandro , Doger Bernard , de Miguel Maria J. , Alvarez Alvarez Rosa Maria , Moreno Victor , Ramón Jorge , Galera López María del Mar , Hernandez-Guerrero Tatiana , Corral Elena , Calvo Emiliano 
Published: June 2022

8581 Background: L is a novel anticancer agent that inhibits trans-activated transcription and modulates the tumor microenvironment. L is approved by the FDA for metastatic SCLC patients (pts) with progressive disease (PD) on or after platinum-based chemotherapy (CT). The LUPER study is assessing the safety, tolerability, and preliminary efficacy of L+P as second-line regimen for SCLC pts after failure of platinum-based CT. Phase 1 data are presented here. Methods: In this phase 1/2 trial (NCT04358237), adult pts with histologically confirmed SCLC, PD to a previous CT-containing regimen (≥4 weeks before study initiation), no prior exposure to immunotherapy, ECOG PS of 0-1, and measurable disease as per RECIST 1.1 are eligible. Pts with treated, stable, and asymptomatic brain metastases (BMs) are allowed. A 3+3 dose-escalation was done to determine the recommended phase 2 dose (RP2D) of L+P. L was dosed at 2.4 mg/m2 and 3.2 mg/m2 IV Q3W in the dose level (DL)1 and 2, respectively, in combination with fixed dose of P (200 mg IV Q3W). The RP2D was the highest DL at which 0/3 pts or ≤1/6 pts experienced dose-limiting toxicities (DLTs) during the first cycle. Treatment was administered until PD, unacceptable toxicity, or consent withdrawal. Secondary endpoints include safety as per CTCAE 5.0, preliminary efficacy, and pharmacokinetics. Results: Thirteen pts were enrolled across 3 hospitals in Spain (DL1, n = 7; DL2, n = 6). Median age was 66 (range 43–78) years, 46.2% were female, 61.5% had ECOG PS of 1, 38.5% had platinum-free interval < 90 days, 30.8% had LDH > upper normal limit, and 15.4% had BMs. One DLT (G3 asthenia) and one G4 neutropenia lasting > 3 days (controlled with G-CSF prophylaxis upon C2, without requiring dose delay or modification) occurred in the DL1. No DLT were reported in the DL2. The RP2D was identified as 3.2 mg/m2 L and 200 mg P IV Q3W. At data cutoff (Jan 21, 2022), 5 (38.4%) pts remained on treatment (1 pt in DL1 discontinued due to COVID-19 in cycle 1). Median duration of treatment was 2.1 (0–11.8) months, 5 (38.5%) pts had ≥8 cycles, and median relative dose intensity of L and P were 91.1% and 95.7%, respectively. Immune-related AEs (G2 pneumonitis; G3 ALT increased) led to P discontinuation in 2 (15.4%) pts. Responses were shown in both DLs, with ORR of 30.8% (1 confirmed complete response and 3 partial responses); 3 pts had stable disease (SD; including 1 patient with SD > 12 weeks) and 5 (38.5%) pts experienced PD. Conclusions: This is the first report to demonstrate a manageable safety profile and preliminary efficacy of second-line L+P for relapsed SCLC pts. This combination warrants further confirmation in the ongoing expansion phase 2. Clinical trial information: NCT04358237.
Circulating tumor DNA (ctDNA) mutations associate with response in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC) treated with talazoparib (TALA) and temozolomide (TMZ).
Authors: Velez Maria A , Cummings Amy Lauren , Mulroy Matthew C , Garon Edward B. , Slamon Dennis J. , Goldman Jonathan W. 
Published: June 2022

8582 Background: Poly (ADP-ribose) polymerase (PARP) inhibition in combination with TMZ is a promising treatment strategy for ES-SCLC. In SCLC models, TALA, a potent PARP inhibitor, exhibits cytotoxic effects by impairing PARP proteins 1/2 and trapping PARP on DNA while TMZ potentiates antitumor response by contributing to genomic instability (Wainberg 2016). A prior analysis of ctDNA in 15 pts treated on trial with TALA and TMZ suggested that mutations in DNA damage repair (DDR) genes occurred with this combination and may associate with response (Mulroy ASCO 2021). Methods: Pts with relapsed or refractory ES-SCLC were treated with TALA 0.75 mg po daily with TMZ 37.5 mg/m2 po on days 1-5 of 28-day cycles in a phase 2 clinical trial (UCLA/TRIO-US L-07, NCT03672773). ctDNA was collected and assessed based on allele frequency and plasma copy number at baseline and every 8 weeks during treatment with the Guardant360 assay (Redwood City, CA). DDR status was defined as a mutation known or likely to result in aberrant expression of ATM or BRCA1/2 (other DDR genes not detected by assay) (Pearl 2015). Germline DDR mutations were evaluated with matched-normal (PBMC) whole exome sequencing (WES) with archival specimens by Tempus (Chicago, IL). Response to treatment was defined by RECIST 1.1 criteria. Fishers exact tests were used to compare proportions of patients, with P-values <0.05 considered statistically significant ( www.r-project.org , Vienna, AU). Results: For 27 pts with evaluable response, 78 ctDNA samples were collected. The most common baseline somatic alterations were mutations in TP53 (23 pts), RB1 (8 pts), ATM (5 pts), and BRCA2 (5 pts). There were no patients with germline DDR mutations. Overall, 22/27 (81.5%) had disease control (DC), including 11 with confirmed partial responses (PR) and 11 with stable disease while 5 had progressive disease. All those with PRs and ctDNA burden >0.2% at baseline experienced a ctDNA decrease at 8 weeks of treatment. DDR mutations were found in 18/27 (66.7%) pts. Of those with ≥ 1 follow-up ctDNA time point collected, 13/17 (76.4%) pts had at least one new mutation detected while on treatment, most commonly in ATM (6 pts). The appearance of new mutations associated with DC (P=0.042) and with a trend towards improved progression free survival (PFS, 5.9 m vs 3.6 m, P=0.099). All 5 pts with DDR mutations present at baseline had DC with TALA and TMZ, and 9/11 (81.8%) of those with PR had DDR mutations detected at some point during the trial, although the trend toward DC enrichment with DDR mutations did not maintain statistical significance (P=0.24). Conclusions: Mutations in DDR genes occur on treatment with TALA and TMZ and may associate with disease control. Validation in a larger cohort will be pursued.
Outcomes of first-line immune checkpoint inhibitors with or without chemotherapy according to KRAS mutational status and PD-L1 expression in patients with advanced NSCLC: FDA pooled analysis.
Authors: Nakajima Erica C. , Ren Yi , Vallejo Jonathon Joseph , Akinboro Oladimeji , Mishra-Kalyani Pallavi Shruti , Larkins Erin A. , Drezner Nicole Lauren , Tang Shenghui , Pazdur Richard , Beaver Julia A. , Singh Harpreet 
Published: June 2022

9001 Background: While existing data suggest a detriment of immune checkpoint inhibitors (ICI) in other targetable mutations in non-small cell lung cancer (NSCLC), limited retrospective analyses suggest patients with Kirsten rat sarcoma oncogene ( KRAS)-mutated NSCLC benefit from ICI in the front-line (1L). To better define this benefit, pooled data from 12 registrational clinical trials investigating 1L ICI with or without chemotherapy (chemo) in patients with documented KRAS status (mutant or wildtype) was evaluated for efficacy of ICI+chemo, ICI alone, and chemo alone. Methods: Pooled data was evaluated for objective response rate (ORR) and overall survival (OS) by KRAS status (mutant, G12C, or wildtype). ORR and 95% confidence intervals (CI) were estimated using Clopper-Pearson method; median OS was estimated using Kaplan-Meier methods. Subgroup analyses were performed using Cox model stratified by KRAS status and PD-L1 status (Positive (combined positive score (CPS) ≥1), Negative (CPS<1), High (CPS≥50), Low (CPS<50)). Results: KRAS mutational status was reported in 1430 patients (61% wildtype, 39% mutated). KRAS G12C was reported in 11% of patients with a KRAS mutation (157/555). Demographics were similar between KRAS mutated, G12C, and wildtype patients. Amongst all patients, 60% were male, 89% white, 60% positive PD-L1, 67% former or current smokers. Table 1 shows outcomes of chemo+ICI, ICI alone, and chemo alone in each population. Conclusions: This retrospective, pooled analysis suggests that patients with KRAS-mutated NSCLC benefit from 1L chemo-ICI similarly to those with KRAS wild-type NSCLC, and should receive combination therapy upfront. Patients with KRAS-mutated NSCLC derived the greatest benefit from the combination of chemo-ICI as compared to ICI or chemo alone. The small number of patients with documented KRAS G12C mutation limits interpretation of the data for this subgroup. Clinical trials investigating targeted therapies for KRAS-mutated NSCLC in the 1L should include a chemo-ICI comparator arm. [Table: see text]