JTO Clinical and Research Reports最新文献

{"title":"Treating Tobacco Dependency in National Health Service Workers in Greater Manchester: An Evaluation of a Bespoke Digital Service","authors":"Kavita Sivabalah MB BCh BAO, MRCP (UK) ,&nbsp;David Crane PhD ,&nbsp;Samantha Neville ,&nbsp;Mandy Hancock MSc ,&nbsp;Anthony Ryan ,&nbsp;Bincy Ajay ,&nbsp;Jane Coyne BA ,&nbsp;Elizabeth Benbow ,&nbsp;Andrea Crossfield MSc ,&nbsp;Sebastian Bate MMath ,&nbsp;Matthew Evison MD","doi":"10.1016/j.jtocrr.2024.100674","DOIUrl":"10.1016/j.jtocrr.2024.100674","url":null,"abstract":"<div><h3>Introduction</h3><p>Treating tobacco dependency in National Health Service (NHS) workers delivers substantial benefits at an individual, population, and health care system level. We report the outcomes from the Greater Manchester Integrated Care Partnership’s tobacco dependency treatment program for NHS workers which includes 6-months’ access to behavioral support and 12 weeks of treatment through a digital application.</p></div><div><h3>Methods</h3><p>Aggregate results for all participants across the program from January 1, 2022, to September 1, 2023, are reported including a deep-dive evaluation of 300 participants recruited to provide chemically validated outcomes.</p></div><div><h3>Results</h3><p>A total of 1567 NHS workers participated in the program within the evaluation period, completing 24,048 sessions with specialist advisors within the application, ordering 18,710 nicotine vape liquids, 6927 nicotine patches, and 297 short-acting nicotine products. Users reported achieving 89,464 smoke-free days, 1,258,069 less cigarettes smoked, and a financial saving of £622,231. The deep-dive evaluation revealed a CO-verified 12-week abstinence rate of 37% (111 of 300).</p></div><div><h3>Conclusion</h3><p>This evaluation provides assurance of clinical effectiveness within a bespoke digital tobacco dependency treatment program for NHS workers across an Integrated Care Partnership.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 6","pages":"Article 100674"},"PeriodicalIF":0.0,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000444/pdfft?md5=7c3c7a54d194921b994c0771480aff7a&pid=1-s2.0-S2666364324000444-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140764914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heart and Lung Dose as Predictors of Overall Survival in Patients With Locally Advanced Lung Cancer. A National Multicenter Study","authors":"Agon Olloni MD, PhD ,&nbsp;Carsten Brink PhD ,&nbsp;Ebbe Laugaard Lorenzen PhD ,&nbsp;Stefan Starup Jeppesen PhD ,&nbsp;Lone Hofmann PhD ,&nbsp;Charlotte Kristiansen MD ,&nbsp;Marianne Marquard Knap MD ,&nbsp;Ditte Sloth Møller PhD ,&nbsp;Lotte Nygård MD, PhD ,&nbsp;Gitte Fredberg Persson MD, PhD ,&nbsp;Rune Slot Thing PhD ,&nbsp;Hella Maria Brøgger Sand MD ,&nbsp;Axel Diederichsen MD, PhD ,&nbsp;Tine Schytte MD, PhD","doi":"10.1016/j.jtocrr.2024.100663","DOIUrl":"10.1016/j.jtocrr.2024.100663","url":null,"abstract":"<div><h3>Introduction</h3><p>It is an ongoing debate how much lung and heart irradiation impact overall survival (OS) after definitive radiotherapy for lung cancer. This study uses a large national cohort of patients with locally advanced NSCLC to investigate the association between OS and irradiation of lung and heart.</p></div><div><h3>Methods</h3><p>Treatment plans were acquired from six Danish radiotherapy centers, and patient characteristics were obtained from national registries. A hybrid segmentation tool automatically delineated the heart and substructures. Dose-volume histograms for all structures were extracted and analyzed using principal component analyses (PCAs). Parameter selection for a multivariable Cox model for OS prediction was performed using cross-validation based on bootstrapping.</p></div><div><h3>Results</h3><p>The population consisted of 644 patients with a median survival of 26 months (95% confidence interval [CI]: 24–29). The cross-validation selected two PCA variables to be included in the multivariable model. PCA1 represented irradiation of the heart and affected OS negatively (hazard ratio, 1.14; 95% CI: 1.04–1.26). PCA2 characterized the left-right balance (right atrium and left ventricle) irradiation, showing better survival for tumors near the right side (hazard ratio, 0.92; 95% CI: 0.84–1.00). Besides the two PCA variables, the multivariable model included age, sex, body-mass index, performance status, tumor dose, and tumor volume.</p></div><div><h3>Conclusions</h3><p>Besides the classic noncardiac risk factors, lung and heart doses had a negative impact on survival, while it is suggested that the left side of the heart is a more radiation dose–sensitive region. The data indicate that overall heart irradiation should be reduced to improve the OS if possible.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 4","pages":"Article 100663"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266636432400033X/pdfft?md5=e293483a3ddac4c0c51545322e9a2609&pid=1-s2.0-S266636432400033X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140280135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphoproteomic Analysis Identified Mutual Phosphorylation of FAK and Src as a Mechanism of Osimertinib Resistance in EGFR-Mutant Lung Cancer","authors":"Takehiro Tozuka MD ,&nbsp;Rintaro Noro MD, PhD ,&nbsp;Keisuke Yoshida PhD ,&nbsp;Satoshi Takahashi MD, PhD ,&nbsp;Mariko Hirao XX ,&nbsp;Kuniko Matsuda XX ,&nbsp;Yasuhiro Kato MD ,&nbsp;Shinji Nakamichi MD, PhD ,&nbsp;Susumu Takeuchi MD, PhD ,&nbsp;Masaru Matsumoto MD, PhD ,&nbsp;Akihiko Miyanaga MD, PhD ,&nbsp;Shinobu Kunugi MD, PhD ,&nbsp;Kazufumi Honda DDS, PhD ,&nbsp;Jun Adachi PhD ,&nbsp;Masahiro Seike MD, PhD","doi":"10.1016/j.jtocrr.2024.100668","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2024.100668","url":null,"abstract":"<div><h3>Introduction</h3><p>Osimertinib is a standard treatment for patients with <em>EGFR</em>-mutant NSCLC. Although some osimertinib resistance mechanisms have been identified, nearly 50% of the mechanisms remain to be elucidated. This study was aimed at identifying non-genetic mechanisms underlying osimertinib resistance.</p></div><div><h3>Methods</h3><p>We established two osimertinib-resistant cell lines from <em>EGFR</em> mutation-positive PC-9 and HCC827 NSCLC cell lines (PC-9OR and HCC827OR, respectively) using a stepwise method. We compared the phosphoproteomic profiles of the osimertinib-resistant and parental cells using mass spectrometry. Upstream kinases were identified using the application Kinase Enrichment Analysis version 3.</p></div><div><h3>Results</h3><p>Phosphoproteomic analysis revealed 80 phosphorylation sites that were mutually up-regulated in PC-9OR and HCC827OR cells. The Kinase Enrichment Analysis version 3 analysis identified focal adhesion kinase (FAK) and proto-oncogene tyrosine-protein kinase Src (Src) as upstream kinases of these up-regulated phosphoproteins. The small-interfering RNA–mediated knockdown of FAK reduced Src phosphorylation and that of Src reduced FAK phosphorylation in both cell lines. Furthermore, FAK- or Src-specific small-interfering RNA treatments restored EGFR phosphorylation in PC-9OR and HCC827OR cells. The combination of FAK and Src inhibitors inhibited PC-9OR and HCC827OR cell proliferation in vitro and suppressed tumor growth in a xenograft mouse model. Immunohistochemistry of tumors from patients with <em>EGFR</em>-mutant NSCLC suggested that phosphorylated FAK and Src are involved in initial and acquired resistance to osimertinib.</p></div><div><h3>Conclusions</h3><p>Phosphoproteomic analysis may help elucidate the mechanisms of resistance to molecular-targeted therapies in lung cancer. Mutual phosphorylation of FAK and Src is involved in osimertinib resistance. Thus, FAK and Src inhibition may be novel treatment strategies for osimertinib-resistant NSCLC.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 4","pages":"Article 100668"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000389/pdfft?md5=7b6560c60e702d1983547e4ee3c5ef18&pid=1-s2.0-S2666364324000389-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140550838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brief Report: Clinical Outcomes by Infusion Timing of Immune Checkpoint Inhibitors in Patients With Locally Advanced NSCLC","authors":"Tsuyoshi Hirata MD ,&nbsp;Yuji Uehara MD ,&nbsp;Taiki Hakozaki MD ,&nbsp;Takayuki Kobayashi MD ,&nbsp;Yuto Terashima MD ,&nbsp;Kageaki Watanabe MD ,&nbsp;Makiko Yomota MD, PhD ,&nbsp;Yukio Hosomi MD, PhD","doi":"10.1016/j.jtocrr.2024.100659","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2024.100659","url":null,"abstract":"<div><h3>Introduction</h3><p>Previous studies reported an association between immune checkpoint inhibitor infusion timing and the treatment effect in metastatic NSCLC. The present study assessed the association between durvalumab infusion timing and survival outcomes in patients with locally advanced NSCLC.</p></div><div><h3>Methods</h3><p>Patients receiving durvalumab after chemoradiotherapy for locally advanced NSCLC at a single institution were retrospectively analyzed, and the association of the proportion of durvalumab infusions greater than or equal to 20% versus less than 20% after 3 <span>PM</span> with progression-free survival (PFS) and overall survival was assessed.</p></div><div><h3>Results</h3><p>A total of 82 patients were included, with a median age of 69 years (interquartile range, 62–74 years); of these, 67 patients (82%) were of male sex, and 78 patients (95%) had a history of smoking. The median number of durvalumab infusions per patient was 16 (interquartile range, 8–24). Patients with at least 20% of their durvalumab infusions after 3 <span>PM</span> (n = 12/82, 15%) had a significantly shorter PFS than those who did not (median: 7.4 mo versus not available [NA]; hazard ratio [HR], 2.43; 95% confidence interval [CI]: 1.11–5.34, <em>p</em> = 0.027), whereas overall survival was shorter among the former compared with the latter group (median: 22.4 versus NA; HR, 1.80; 95% CI: 0.73–4.42, <em>p</em> = 0.20). In addition, both backward stepwise multivariable analysis and propensity score–matching analysis revealed that receiving at least 20% of durvalumab infusions after 3 <span>PM</span> was significantly associated with worse PFS (HR, 2.54; 95% CI: 1.03–5.67, <em>p</em> = 0.047; and HR, 4.64; 95% CI: 1.95–11.04; <em>p</em> &lt; 0.001, respectively).</p></div><div><h3>Conclusions</h3><p>The time of day of durvalumab infusions may impact survival outcomes in patients with locally advanced NSCLC.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 4","pages":"Article 100659"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000298/pdfft?md5=d84cbc04706013262d06e8a2bc481903&pid=1-s2.0-S2666364324000298-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140351009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Checkpoint Inhibitor Monotherapy in Potentially Trial-Eligible or Trial-Ineligible Patients With Metastatic NSCLC in the German Prospective CRISP Registry Real-World Cohort (AIO-TRK-0315)","authors":"Frank Griesinger MD, PhD ,&nbsp;Martin Sebastian MD ,&nbsp;Wolfgang M. Brueckl MD, PhD ,&nbsp;Horst-Dieter Hummel MD, PhD ,&nbsp;Bastian Jaeschke MD ,&nbsp;Jens Kern MD ,&nbsp;Claas Wesseler MD ,&nbsp;Martina Jänicke PdD ,&nbsp;Annette Fleitz PhD ,&nbsp;Stefan Zacharias PhD ,&nbsp;Annette Hipper PhD ,&nbsp;Annika Groth MD, PhD ,&nbsp;Wilko Weichert MD, PhD ,&nbsp;Steffen Dörfel ,&nbsp;Volker Petersen MD ,&nbsp;Jan Schröder MD ,&nbsp;Jochen Wilke MD ,&nbsp;Wilfried E.E. Eberhardt MD, PhD ,&nbsp;Michael Thomas MD, PhD ,&nbsp;Matthias Zeth","doi":"10.1016/j.jtocrr.2023.100626","DOIUrl":"10.1016/j.jtocrr.2023.100626","url":null,"abstract":"<div><h3>Introduction</h3><p>Patients with metastatic NSCLC (mNSCLC) treated with immune checkpoint inhibitors in clinical practice may often not meet the strict inclusion criteria of clinical trials. Our aim was to assess the trial eligibility of patients with mNSCLC treated with pembrolizumab monotherapy in real-world and to compare the outcome of “trial-ineligible” and “potentially trial-eligible” patients.</p></div><div><h3>Methods</h3><p>Data from the prospective, clinical research platform CRISP were used to compare patient characteristics, treatment, and outcome of patients with programmed cell death-ligand 1 tumor proportion score greater than or equal to 50% tumors treated with pembrolizumab monotherapy who are deemed either “potentially trial-eligible” or “trial-ineligible” according to inclusion and exclusion criteria of the registrational studies (KEYNOTE-024 and -042).</p></div><div><h3>Results</h3><p>Of 746 patients included, 343 patients (46.0%) were classified as “trial-ineligible” and had significantly worse outcomes compared with “potentially trial-eligible” patients (n = 403, 54.0%): median progression-free survival: 6.2 (95% confidence interval [CI]: 5.2–8.4) versus 10.3 (95% CI: 8.4–13.8) months, hazard ratio (trial-ineligible versus potentially trial-eligible) of 1.43 (95% CI: 1.19–1.72), <em>p</em> less than 0.001; median overall survival: 15.9 (95% CI: 11.4–20.3) versus 25.3 (95% CI: 19.8–30.4) months, hazard ratio of 1.36 (95% CI: 1.10–1.67), <em>p</em> equals 0.004.</p></div><div><h3>Conclusions</h3><p>Our data reveal that a considerable proportion of patients with mNSCLC are not eligible to participate in a clinical trial and were found to have worse outcomes than potentially trial-eligible patients, whose outcomes were comparable with those obtained from pivotal clinical trials. This is of substantial clinical relevance for physicians discussing outcomes to be expected with their patients and stresses the need for real-world effectiveness analyses.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 4","pages":"Article 100626"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364323001698/pdfft?md5=5b8cc1593fb9bfb461f4fe4c69a65c3a&pid=1-s2.0-S2666364323001698-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139191820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brief Report: Risk of Recurrent Interstitial Lung Disease From Osimertinib Versus Erlotinib Rechallenge After Symptomatic Osimertinib-Induced Interstitial Lung Disease","authors":"Molly S.C. Li M.B.B.S. ,&nbsp;Kirsty W.C. Lee MBChB ,&nbsp;Kevin K.S. Mok MBChB ,&nbsp;Herbert H.F. Loong M.B.B.S. ,&nbsp;K.C. Lam MBChB ,&nbsp;Florence S.T. Mok M.B.B.S. ,&nbsp;Landon L. Chan MBChB ,&nbsp;Y.M. Lau M.B.B.S. ,&nbsp;K.P. Chan MBChB ,&nbsp;Joyce T.Y. Ng MBChB ,&nbsp;Wesley K.Y. Wong M.B.B.S. ,&nbsp;Benjamin H.W. Lam M.B.B.S. ,&nbsp;Allen C.C. Chen BM ,&nbsp;Matthew M.P. Lee MBChB ,&nbsp;Olivia H. Chen MD, PhD ,&nbsp;Tony S.K. Mok MD","doi":"10.1016/j.jtocrr.2024.100648","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2024.100648","url":null,"abstract":"<div><h3>Introduction</h3><p>Interstitial lung disease (ILD) is the most frequent cause of drug-related mortality from EGFR tyrosine kinase inhibitors (TKIs). Yet, for patients with symptomatic osimertinib-induced ILD, the risk of recurrent ILD associated with EGFR TKI rechallenge, either with osimertinib or another TKI, such as erlotinib, is unclear.</p></div><div><h3>Methods</h3><p>Retrospective study of 913 patients who received osimertinib treatment for <em>EGFR</em> mutation-positive NSCLC. Clinical characteristics, ILD treatment history, and subsequent anticancer therapy of patients with symptomatic osimertinib-induced ILD were collated. The primary end point was to compare the incidence of recurrent ILD with osimertinib versus erlotinib rechallenge.</p></div><div><h3>Results</h3><p>Of 913 patients, 35 (3.8%) had symptomatic osimertinib-induced ILD, of which 12 (34%), 15 (43%), and eight (23%) had grade 2, 3 to 4, and 5 ILD, respectively. On ILD recovery, 17 patients had EGFR TKI rechallenge with eight received osimertinib and nine received erlotinib. The risk of recurrent ILD was higher with osimertinib rechallenge than erlotinib (<em>p</em> = 0.0498). Of eight, five (63%) developed recurrent ILD on osimertinib rechallenge, including three patients with fatal outcomes. In contrast, only one of nine patients (11%) treated with erlotinib had recurrent ILD. Median time to second ILD occurrence was 4.7 (range 0.7–12) weeks. Median time-to-treatment failure of patients with erlotinib rechallenge was 13.2 months (95% confidence interval: 8.6–15.0).</p></div><div><h3>Conclusions</h3><p>The risk of recurrent ILD was considerably higher with osimertinib rechallenge than erlotinib. Osimertinib rechallenge should be avoided, whereas erlotinib may be considered in patients with symptomatic osimertinib-induced ILD.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 4","pages":"Article 100648"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000183/pdfft?md5=a61f22993f5c7bf6be994155930c4030&pid=1-s2.0-S2666364324000183-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140332581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Tumor Immune Microenvironment Is Associated With Recurrence in Early-Stage Lung Adenocarcinoma","authors":"Hiroaki Kanemura MD, MPH, PhD ,&nbsp;Toshihide Yokoyama MD ,&nbsp;Ryu Nakajima MD, PhD ,&nbsp;Atsushi Nakamura MD, PhD ,&nbsp;Hiroaki Kuroda MD, PhD ,&nbsp;Yoshitaka Kitamura MD, PhD ,&nbsp;Hiroyasu Shoda MD, PhD ,&nbsp;Nobuaki Mamesaya MD, PhD ,&nbsp;Yoshihiro Miyata MD, PhD ,&nbsp;Tatsuro Okamoto MD, PhD ,&nbsp;Kyoichi Okishio MD, PhD ,&nbsp;Masahide Oki MD, PhD ,&nbsp;Yuichi Sakairi MD, PhD ,&nbsp;Toyofumi Fengshi Chen-Yoshikawa MD, PhD ,&nbsp;Tadashi Aoki MD ,&nbsp;Tatsuo Ohira MD, PhD ,&nbsp;Isao Matsumoto MD, PhD ,&nbsp;Kiyonobu Ueno MD, PhD ,&nbsp;Takuro Miyazaki MD, PhD ,&nbsp;Haruhisa Matsuguma MD, PhD ,&nbsp;Masayuki Takeda MD, PhD","doi":"10.1016/j.jtocrr.2024.100658","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2024.100658","url":null,"abstract":"<div><h3>Introduction</h3><p>Immune checkpoint inhibitors have recently been approved for the treatment of early-stage NSCLC in the perioperative setting on the basis of phase 3 trials. However, the characteristics of such patients who are susceptible to recurrence after adjuvant chemotherapy or who are likely to benefit from postoperative immunotherapy have remained unclear.</p></div><div><h3>Methods</h3><p>This biomarker study (WJOG12219LTR) was designed to evaluate cancer stem cell markers (CD44 and CD133), programmed death-ligand 1 (PD-L1) expression on tumor cells, CD8 expression on tumor-infiltrating lymphocytes, and tumor mutation burden in completely resected stage II to IIIA NSCLC with the use of archived DNA and tissue samples from the prospective WJOG4107 trial. Tumors were classified as inflamed or noninflamed on the basis of the PD-L1 tumor proportion score and CD8⁺ tumor-infiltrating lymphocyte density. The association between each potential biomarker and relapse-free survival (RFS) during adjuvant chemotherapy was assessed by Kaplan-Meier analysis.</p></div><div><h3>Results</h3><p>A total of 117 patients were included in this study. The median RFS was not reached (95% confidence intervals [CI]: 22.4 mo–not reached; n = 39) and 23.7 months (95% CI: 14.5–43.6; n = 41) in patients with inflamed or noninflamed adenocarcinoma, respectively (log-rank <em>p</em> = 0.02, hazard ratio of 0.52 [95% CI: 0.29–0.93]). Analysis of the combination of tumor inflammation category and <em>TP53</em> mutation status revealed that inflamed tumors without <em>TP53</em> mutations were associated with the longest RFS.</p></div><div><h3>Conclusions</h3><p>PD-L1 expression on tumor cells, CD8⁺ T cell infiltration, and <em>TP53</em> mutation status may help identify patients with early-stage NSCLC susceptible to recurrence after adjuvant chemotherapy.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 4","pages":"Article 100658"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000286/pdfft?md5=d33532546693496a34f932f2317fecfb&pid=1-s2.0-S2666364324000286-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140548984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing Opportunity: Pilot Intervention to Improve Lung Cancer Screening for Women Undergoing Breast Screening Mammography","authors":"Lye-Yeng Wong MD ,&nbsp;Tiffany Yue BS ,&nbsp;Ghazal Aghagoli BS ,&nbsp;Ioana Baiu MD ,&nbsp;Laura Shula PA-C ,&nbsp;Angela Lee NP ,&nbsp;Natalie S. Lui MD ,&nbsp;Leah M. Backhus MD, MPH","doi":"10.1016/j.jtocrr.2024.100671","DOIUrl":"10.1016/j.jtocrr.2024.100671","url":null,"abstract":"<div><h3>Introduction</h3><p>The screening mammogram could be a “teachable moment” to improve lung cancer screening (LCS) uptake. The aim of our project was to combine patient self-referral with eligibility identification by providers as a two-pronged approach to increase rates of LCS among eligible women.</p></div><div><h3>Methods</h3><p>LCS education materials were created to stimulate patient education and encourage self-referral. Chart review of patients scheduled for screening mammography was performed to identify patients who met LCS criteria. The primary outcome was rate of acceptance of targeted interventions as measured by qualitative survey material and rate of LCS uptake.</p></div><div><h3>Results</h3><p>Between August 2022 and August 2023, 116 patients were identified by providers for potential eligibility for LCS and 34 patients (29.3%) deemed eligible based on the U.S. Preventative Services Task Force 2021 guidelines. There were 19 patients (56%) who completed LCS with three patients (16%) with screen-detected nodules that led to further workup. Post-implementation qualitative survey results reveal that 100% of the participants rated their shared decision-making visit experience as “very helpful” and 67% responded “very likely” to seek simultaneous breast and LCS in the future. Informational materials were rated as 80% favorable among all respondents; however, the rate of self-referral alone was 0%. The combined rates of eligible patients lost to follow-up or refusal was 24%.</p></div><div><h3>Conclusion</h3><p>The self-referral aspect of the intervention revealed that patients are unlikely to self-refer for LCS. Nevertheless, patients undergoing screening mammograms individually identified for LCS were very responsive to learning more about dual screening.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 6","pages":"Article 100671"},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000419/pdfft?md5=3b5d1bb05b435fdd0c1018b1f30bbc6f&pid=1-s2.0-S2666364324000419-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140406595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cabozantinib Plus Atezolizumab or Cabozantinib Alone in Patients With Advanced NSCLC Previously Treated With an Immune Checkpoint Inhibitor: Results From the Phase 1b COSMIC-021 Study","authors":"","doi":"10.1016/j.jtocrr.2024.100666","DOIUrl":"10.1016/j.jtocrr.2024.100666","url":null,"abstract":"<div><h3>Introduction</h3><p>We evaluated efficacy and safety of cabozantinib plus atezolizumab or cabozantinib alone in advanced NSCLC previously treated with an immune checkpoint inhibitor (ICI).</p></div><div><h3>Methods</h3><p>COSMIC-021 (NCT03170960) is a phase 1b, multicenter study in advanced solid tumors. This analysis included patients with stage IV non-squamous NSCLC without actionable genomic aberrations in <em>EGFR, ALK, ROS1</em>, or <em>BRAF</em>-<em>V600E</em> who progressed on one prior ICI and less than or equal to two prior lines of systemic anticancer therapy. Patients received cabozantinib 40 mg orally/day plus atezolizumab 1200 mg intravenously every three weeks (combination cohort) or cabozantinib 60 mg orally/day (single-agent cabozantinib cohort). Primary end point of the combination cohort was objective response rate per Response Evaluation Criteria in Solid Tumors v1.1 by investigator. Outcomes in the single-agent cabozantinib cohort were exploratory.</p></div><div><h3>Results</h3><p>Eighty-one patients assigned to combination therapy and 31 assigned to single-agent cabozantinib received greater than or equal to one dose of study treatment. Median (range) follow-up was 26.1 months (12.1–44.2) and 22.4 months (1.5–29.0), respectively. Objective response rate was 20% (95% confidence interval: 11.7%–30.1%) in combination cohort and 6% (95% confidence interval: 0.8%–21.4%) in single-agent cabozantinib cohort. Treatment-related adverse events (TRAEs) occurred in 86% of patients in the combination cohort and 90% in the single-agent cabozantinib cohort; grade 3/4 TRAEs were 44% and 48%, respectively. There were two grade 5 TRAEs: pneumonitis (n = 1, combination) and gastric ulcer hemorrhage (n = 1, single-agent). Neither PD-L1 expression in tumor cells nor tumor mutation burden correlated with outcomes.</p></div><div><h3>Conclusions</h3><p>Cabozantinib plus atezolizumab demonstrated modest clinical activity and manageable toxicity in advanced NSCLC after progression on prior ICI.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 10","pages":"Article 100666"},"PeriodicalIF":3.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000365/pdfft?md5=8cbe6ed5619b31f78dc83383f890cb04&pid=1-s2.0-S2666364324000365-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140277898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brief Report: Long-Term Follow-Up of Adjuvant Pembrolizumab After Locally Ablative Therapy for Oligometastatic NSCLC","authors":"David J. Cantor MD, PhD ,&nbsp;Christiana Davis MD ,&nbsp;Christine Ciunci MD, MSCE ,&nbsp;Charu Aggarwal MD, MPH ,&nbsp;Tracey Evans MD ,&nbsp;Roger B. Cohen MD ,&nbsp;Joshua M. Bauml MD ,&nbsp;Corey J. Langer MD","doi":"10.1016/j.jtocrr.2024.100667","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2024.100667","url":null,"abstract":"<div><h3>Introduction</h3><p>Patients with oligometastatic NSCLC benefit from locally ablative therapies (LAT); the role of adjuvant systemic therapies, however, remains less clear. In a single-arm, phase II clinical trial, we found that patients with oligometastatic NSCLC treated with a year of pembrolizumab after LAT had superior progression-free survival (PFS) compared with a historical control cohort. Herein, we present long-term follow-up on PFS and overall survival (OS).</p></div><div><h3>Methods</h3><p>From February 1, 2015, to September 30, 2017, 45 patients with synchronous or metachronous oligometastatic (≤4 metastatic sites) NSCLC treated with LAT to all sites received adjuvant pembrolizumab every 21 days for up to 16 cycles. The primary efficacy end point was PFS from the start of pembrolizumab. Secondary end points included OS and safety. Median duration of follow-up was 66 months, and data cutoff was December 1, 2022.</p></div><div><h3>Results</h3><p>A total of 45 patients were enrolled and treated with pembrolizumab after LAT (median age, 64 y [range, 46–82]; 21 women [47%]; 31 with a solitary oligometastatic site [69%]). At the data cutoff, 32 patients had progressive disease, 19 patients had died, and 13 patients had no evidence of relapse. Median PFS was 19.7 months (95% confidence interval: 7.6–31.7 mo); median OS was not reached (95% confidence interval: 37.7 mo–not reached). OS at 5 years was 60.0% (SE, 7.4%). Metachronous oligometastatic disease was associated with improved OS and PFS through Cox proportional hazard models.</p></div><div><h3>Conclusions</h3><p>Pembrolizumab after LAT for oligometastatic NSCLC results in promising PFS and OS with a tolerable safety profile.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 6","pages":"Article 100667"},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000377/pdfft?md5=0687f20c1fa0d78bc4ac583db50c81dd&pid=1-s2.0-S2666364324000377-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141068189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}