Pub Date : 2025-04-09DOI: 10.1016/j.jtocrr.2025.100834
Sabine Raimann MD , Sämi Schär PhD , Stefanie Hayoz PhD , Matthias Guckenberger MD , Tobias Finazzi MD, PhD , Isabelle Opitz MD , Sabine Schmid MD , Michael Mark MD , Alfredo Addeo MD , Laetitia A. Mauti MD, PhD , Daniel C. Betticher MD , Hans-Beat Ris MD , Roger Stupp MD , Alessandra Curioni-Fontecedro MD , Solange Peters MD, PhD , Martin Früh MD , Sacha I. Rothschild MD, PhD , Miklos Pless MD , David König MD
Introduction
Neoadjuvant or perioperative treatment, including an immune checkpoint inhibitor (ICI), has emerged as a new standard for patients with resectable stage III NSCLC. Nevertheless, approximately 20% of patients who start neoadjuvant chemo-immunotherapy will not undergo definitive surgery. Little is known about these patients.
Methods
We analyzed outcomes of patients without definitive surgery from five Swiss Group for Clinical Cancer Research (SAKK) trials that investigated different neoadjuvant treatment modalities in patients with resectable stage III-N2 NSCLC. Study treatment included neoadjuvant cisplatin-docetaxel chemotherapy (with or without radiotherapy), either combined with peri-operative durvalumab in the SAKK 16/14 trial (n = 68) or without an ICI (non-ICI trials, n = 431).
Results
Of the 499 patients, 102 (20%) did not have definitive surgery. Cancellation of surgery occurred in a similar proportion of patients with or without neoadjuvant ICI (19% versus 21%, p = 0.9). Reasons were in non-ICI trials and SAKK 16/14: disease progression (47% and 54%), nonresectability (18% and 8%), medical reasons (17% and 31%), and unknown (18% and 8%), respectively. Of these patients, no patient in SAKK 16/14 and 17 patients (19%) in the non-ICI trials received curative-intended salvage therapy. Three-year overall survival was higher in patients who had definitive surgery compared with those who did not: 78% versus 32% (SAKK 16/14) and 54% versus 10% (non-ICI trials).
Conclusions
In our pooled analysis, patients with definitive surgery had higher survival rates than those without definitive surgery. Prognosis in patients without definitive surgery seems to have improved in the era of ICI.
{"title":"Outcomes in Patients With Resectable Stage III NSCLC Who Did Not Have Definitive Surgery After Neoadjuvant Treatment—A Retrospective Analysis of the SAKK Trials 16/96, 16/00, 16/01, 16/08, and 16/14: A Brief Report","authors":"Sabine Raimann MD , Sämi Schär PhD , Stefanie Hayoz PhD , Matthias Guckenberger MD , Tobias Finazzi MD, PhD , Isabelle Opitz MD , Sabine Schmid MD , Michael Mark MD , Alfredo Addeo MD , Laetitia A. Mauti MD, PhD , Daniel C. Betticher MD , Hans-Beat Ris MD , Roger Stupp MD , Alessandra Curioni-Fontecedro MD , Solange Peters MD, PhD , Martin Früh MD , Sacha I. Rothschild MD, PhD , Miklos Pless MD , David König MD","doi":"10.1016/j.jtocrr.2025.100834","DOIUrl":"10.1016/j.jtocrr.2025.100834","url":null,"abstract":"<div><h3>Introduction</h3><div>Neoadjuvant or perioperative treatment, including an immune checkpoint inhibitor (ICI), has emerged as a new standard for patients with resectable stage III NSCLC. Nevertheless, approximately 20% of patients who start neoadjuvant chemo-immunotherapy will not undergo definitive surgery. Little is known about these patients.</div></div><div><h3>Methods</h3><div>We analyzed outcomes of patients without definitive surgery from five Swiss Group for Clinical Cancer Research (SAKK) trials that investigated different neoadjuvant treatment modalities in patients with resectable stage III-N2 NSCLC. Study treatment included neoadjuvant cisplatin-docetaxel chemotherapy (with or without radiotherapy), either combined with peri-operative durvalumab in the SAKK 16/14 trial (n = 68) or without an ICI (non-ICI trials, n = 431).</div></div><div><h3>Results</h3><div>Of the 499 patients, 102 (20%) did not have definitive surgery. Cancellation of surgery occurred in a similar proportion of patients with or without neoadjuvant ICI (19% versus 21%, <em>p</em> = 0.9). Reasons were in non-ICI trials and SAKK 16/14: disease progression (47% and 54%), nonresectability (18% and 8%), medical reasons (17% and 31%), and unknown (18% and 8%), respectively. Of these patients, no patient in SAKK 16/14 and 17 patients (19%) in the non-ICI trials received curative-intended salvage therapy. Three-year overall survival was higher in patients who had definitive surgery compared with those who did not: 78% versus 32% (SAKK 16/14) and 54% versus 10% (non-ICI trials).</div></div><div><h3>Conclusions</h3><div>In our pooled analysis, patients with definitive surgery had higher survival rates than those without definitive surgery. Prognosis in patients without definitive surgery seems to have improved in the era of ICI.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 6","pages":"Article 100834"},"PeriodicalIF":3.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-09DOI: 10.1016/j.jtocrr.2025.100833
Angelos Vasilopoulos BS , Alexander Pohlman MD , Ayham Odeh MD , K. Robert Shen MD , Julia M. Coughlin MD , Zaid M. Abdelsattar MD, MS, FACS
Introduction
Osimertinib is now approved as adjuvant therapy for stage IB to III NSCLC with EGFR mutations. Nevertheless, this treatment is lengthy and expensive. Its cost-effectiveness profile as monotherapy versus combination with chemotherapy is unknown. In this context, we investigate the cost-effectiveness of adjuvant osimertinib with and without chemotherapy for NSCLC.
Methods
A set of Markov models was established to predict the cost-effectiveness of these different regimens. Data were sourced from the ADAURA trial’s publications and protocols. Health outcomes were quantified as quality-adjusted life-years (QALYs). Costs and incremental cost-effectiveness ratios (ICERs) were estimated in U.S. dollars (USD) and USD per QALY, respectively. Deterministic and probabilistic sensitivity analyses were performed. Data from the Surveillance, Epidemiology, and End Results Program were used to predict additional costs to the U.S. health care system.
Results
Compared with treatment with chemotherapy alone, treatment with osimertinib plus chemotherapy yielded 5.86 QALYs with incremental costs of $414,607.69 (ICER = $380,347.85 per QALY). Treatment with osimertinib alone yielded 6.63 QALYs with an incremental cost of $402,224.32 (ICER = $213,447.59 per QALY). Osimertinib is only likely to be cost-effective if the willingness-to-pay threshold per QALY is $200,000 or more. The price of osimertinib had the strongest influence on cost-effectiveness. On the basis of Surveillance, Epidemiology, and End Results Program data, these practices may cost the U.S. health care system an additional 8.9 billion USD/year.
Conclusions
Adjuvant osimertinib alone is more cost-effective than combination therapy, but only if the willingness-to-pay is high. A reduction in the price of osimertinib would improve its cost-effectiveness profile.
{"title":"Cost-Effectiveness of Adjuvant Osimertinib With and Without Chemotherapy for Surgically Resected NSCLC","authors":"Angelos Vasilopoulos BS , Alexander Pohlman MD , Ayham Odeh MD , K. Robert Shen MD , Julia M. Coughlin MD , Zaid M. Abdelsattar MD, MS, FACS","doi":"10.1016/j.jtocrr.2025.100833","DOIUrl":"10.1016/j.jtocrr.2025.100833","url":null,"abstract":"<div><h3>Introduction</h3><div>Osimertinib is now approved as adjuvant therapy for stage IB to III NSCLC with <em>EGFR</em> mutations. Nevertheless, this treatment is lengthy and expensive. Its cost-effectiveness profile as monotherapy versus combination with chemotherapy is unknown. In this context, we investigate the cost-effectiveness of adjuvant osimertinib with and without chemotherapy for NSCLC.</div></div><div><h3>Methods</h3><div>A set of Markov models was established to predict the cost-effectiveness of these different regimens. Data were sourced from the ADAURA trial’s publications and protocols. Health outcomes were quantified as quality-adjusted life-years (QALYs). Costs and incremental cost-effectiveness ratios (ICERs) were estimated in U.S. dollars (USD) and USD per QALY, respectively. Deterministic and probabilistic sensitivity analyses were performed. Data from the Surveillance, Epidemiology, and End Results Program were used to predict additional costs to the U.S. health care system.</div></div><div><h3>Results</h3><div>Compared with treatment with chemotherapy alone, treatment with osimertinib plus chemotherapy yielded 5.86 QALYs with incremental costs of $414,607.69 (ICER = $380,347.85 per QALY). Treatment with osimertinib alone yielded 6.63 QALYs with an incremental cost of $402,224.32 (ICER = $213,447.59 per QALY). Osimertinib is only likely to be cost-effective if the willingness-to-pay threshold per QALY is $200,000 or more. The price of osimertinib had the strongest influence on cost-effectiveness. On the basis of Surveillance, Epidemiology, and End Results Program data, these practices may cost the U.S. health care system an additional 8.9 billion USD/year.</div></div><div><h3>Conclusions</h3><div>Adjuvant osimertinib alone is more cost-effective than combination therapy, but only if the willingness-to-pay is high. A reduction in the price of osimertinib would improve its cost-effectiveness profile.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 6","pages":"Article 100833"},"PeriodicalIF":3.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-20DOI: 10.1016/j.jtocrr.2025.100825
V. Paul Doria-Rose DVM, PhD , Gerard A. Silvestri MD, MS , Danielle D. Durham PhD , Philip Connor BS , Lenka Goldman MSE , Lindsey Enewold PhD, MPH , Farhood Farjah MD, MPH , Eric A. Miller PhD, MSPH , Michael Simanowith MD , Robert A. Smith PhD , Louise M. Henderson PhD, MSPH , Raymond U. Osarogiagbon M.B.B.S., FASCO , Ella A. Kazerooni MD, MS , Andrew Ward PhD, MPH , Paul Pinsky PhD
Introduction
Lung cancer screening has been recommended by the United States Preventive Services Taskforce since 2013. The Centers for Medicare and Medicaid Services coverage decision in early 2015 required data submission to a Centers for Medicare and Medicaid Services–approved registry for facilities to receive payment for screening. Only the American College of Radiology’s Lung Cancer Screening Registry (LCSR) received approval for this purpose. Some LCSR elements, such as race, ethnicity, downstream diagnostic procedures, and cancer outcomes, were underreported.
Methods
To address underreporting, we linked data from the LCSR to Medicare and Surveillance, Epidemiology, and End Results cancer registry data from 2015 to 2021. We created two different cohorts of individuals aged 65 years and older: (1) those who were enrolled in Medicare fee-for-service plans with parts A and B coverage at the time of at least one LCSR-reported screen, and (2) Medicare beneficiaries (regardless of whether fee-for-service or managed care) living within a Surveillance, Epidemiology, and End Results catchment area at the time of at least one LCSR-reported screen. We compared the characteristics of individuals in the linked cohorts with those of all individuals in the LCSR aged 65 years and over.
Results
Demographic, smoking history, and screening examination data elements in the linked data were generally similar to those in the overall LCSR.
Conclusions
On the basis of these results, the linked populations seem to be generally representative of older individuals in the LCSR. These unique data linkages provide an unprecedented opportunity to better understand the early implementation of lung cancer screening in the United States.
{"title":"The United States’ Early Experience With Lung Cancer Screening—Creation of a National Data Linkage: A Brief Report","authors":"V. Paul Doria-Rose DVM, PhD , Gerard A. Silvestri MD, MS , Danielle D. Durham PhD , Philip Connor BS , Lenka Goldman MSE , Lindsey Enewold PhD, MPH , Farhood Farjah MD, MPH , Eric A. Miller PhD, MSPH , Michael Simanowith MD , Robert A. Smith PhD , Louise M. Henderson PhD, MSPH , Raymond U. Osarogiagbon M.B.B.S., FASCO , Ella A. Kazerooni MD, MS , Andrew Ward PhD, MPH , Paul Pinsky PhD","doi":"10.1016/j.jtocrr.2025.100825","DOIUrl":"10.1016/j.jtocrr.2025.100825","url":null,"abstract":"<div><h3>Introduction</h3><div>Lung cancer screening has been recommended by the United States Preventive Services Taskforce since 2013. The Centers for Medicare and Medicaid Services coverage decision in early 2015 required data submission to a Centers for Medicare and Medicaid Services–approved registry for facilities to receive payment for screening. Only the American College of Radiology’s Lung Cancer Screening Registry (LCSR) received approval for this purpose. Some LCSR elements, such as race, ethnicity, downstream diagnostic procedures, and cancer outcomes, were underreported.</div></div><div><h3>Methods</h3><div>To address underreporting, we linked data from the LCSR to Medicare and Surveillance, Epidemiology, and End Results cancer registry data from 2015 to 2021. We created two different cohorts of individuals aged 65 years and older: (1) those who were enrolled in Medicare fee-for-service plans with parts A and B coverage at the time of at least one LCSR-reported screen, and (2) Medicare beneficiaries (regardless of whether fee-for-service or managed care) living within a Surveillance, Epidemiology, and End Results catchment area at the time of at least one LCSR-reported screen. We compared the characteristics of individuals in the linked cohorts with those of all individuals in the LCSR aged 65 years and over.</div></div><div><h3>Results</h3><div>Demographic, smoking history, and screening examination data elements in the linked data were generally similar to those in the overall LCSR.</div></div><div><h3>Conclusions</h3><div>On the basis of these results, the linked populations seem to be generally representative of older individuals in the LCSR. These unique data linkages provide an unprecedented opportunity to better understand the early implementation of lung cancer screening in the United States.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 6","pages":"Article 100825"},"PeriodicalIF":3.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-20DOI: 10.1016/j.jtocrr.2025.100826
Jia Liao MD , Song Wu MD , Yi Min MD , Yiran Li MD , Yuanhang Nie MD , Quwen Chen MD , Zhiliang Mao MD , Qinglan Zong MS , Ning Gao MS , Ding Zhang PhD , Weiquan Liang MD
Introduction
MET exon 14 (METex14) skipping mutations are observed in approximately 0.9% to 4% of patients with NSCLC. This study aimed to compare the detection rates of METex14 skipping in Chinese patients with lung cancer using DNA-based next-generation sequencing (NGS) with capture-based library construction and synchronous DNA-based and RNA-based NGS with amplicon-based library construction.
Methods
A total of 11,330 tissue samples from 11,330 Chinese patients with lung cancer were included in the study to confirm the presence of METex14 skipping. Simultaneously, MET immunohistochemistry testing was performed on 30 patients.
Results
The highest detection rate of METex14 skipping was observed in the synchronous DNA and RNA-based NGS with amplicon-based library construction, reaching 2.20%. A total of 45 different variants leading to METex14 skipping were detected at the DNA level. These variants were widely distributed across a 197–base pair DNA sequence. In the overall population, the incidence of METex14 skipping was significantly higher in individuals aged 60 years and above (p < 0.0001) and needle biopsy samples (p < 0.0001) and reported no significant association with gender and tumor location. A positive correlation was observed between microsatellite instability–high and METex14 skipping (p < 0.0001).
Conclusions
The mutations causing METex14 skipping exhibit diversity in terms of variant types and are widely distributed across various genomic regions. Synchronous DNA-based and RNA-based NGS is considered the optimal method for detecting METex14 skipping. Furthermore, METex14 skipping is enriched in specific populations, including individuals aged 60 years and above, with advanced-stage disease and a microsatellite instability-high status.
{"title":"The Landscape of MET Exon 14 Skipping Mutations in Patients With Lung Cancer Identified by Next-Generation Sequencing","authors":"Jia Liao MD , Song Wu MD , Yi Min MD , Yiran Li MD , Yuanhang Nie MD , Quwen Chen MD , Zhiliang Mao MD , Qinglan Zong MS , Ning Gao MS , Ding Zhang PhD , Weiquan Liang MD","doi":"10.1016/j.jtocrr.2025.100826","DOIUrl":"10.1016/j.jtocrr.2025.100826","url":null,"abstract":"<div><h3>Introduction</h3><div><em>MET</em> exon 14 (<em>MET</em>ex14) skipping mutations are observed in approximately 0.9% to 4% of patients with NSCLC. This study aimed to compare the detection rates of <em>MET</em>ex14 skipping in Chinese patients with lung cancer using DNA-based next-generation sequencing (NGS) with capture-based library construction and synchronous DNA-based and RNA-based NGS with amplicon-based library construction.</div></div><div><h3>Methods</h3><div>A total of 11,330 tissue samples from 11,330 Chinese patients with lung cancer were included in the study to confirm the presence of <em>MET</em>ex14 skipping. Simultaneously, MET immunohistochemistry testing was performed on 30 patients.</div></div><div><h3>Results</h3><div>The highest detection rate of <em>MET</em>ex14 skipping was observed in the synchronous DNA and RNA-based NGS with amplicon-based library construction, reaching 2.20%. A total of 45 different variants leading to <em>MET</em>ex14 skipping were detected at the DNA level. These variants were widely distributed across a 197–base pair DNA sequence. In the overall population, the incidence of <em>MET</em>ex14 skipping was significantly higher in individuals aged 60 years and above (<em>p</em> < 0.0001) and needle biopsy samples (<em>p</em> < 0.0001) and reported no significant association with gender and tumor location. A positive correlation was observed between microsatellite instability–high and <em>MET</em>ex14 skipping (<em>p</em> < 0.0001).</div></div><div><h3>Conclusions</h3><div>The mutations causing <em>MET</em>ex14 skipping exhibit diversity in terms of variant types and are widely distributed across various genomic regions. Synchronous DNA-based and RNA-based NGS is considered the optimal method for detecting <em>MET</em>ex14 skipping. Furthermore, <em>MET</em>ex14 skipping is enriched in specific populations, including individuals aged 60 years and above, with advanced-stage disease and a microsatellite instability-high status.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 7","pages":"Article 100826"},"PeriodicalIF":3.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemoradiotherapy (CRT) followed by durvalumab is the standard of care for unresectable locally advanced NSCLC. Limited prospective data have been reported on intensity-modulated radiotherapy (IMRT)–adapted CRT in the immunotherapy era.
Methods
In this multicenter prospective observational study, patients underwent IMRT-adapted CRT (platinum-doublet chemotherapy plus 60 Gy IMRT in 30 fractions under a prespecified radiation protocol), followed by consolidative durvalumab. The primary outcome was the durvalumab introduction rate within 42 days post-CRT.
Results
Thirty-two patients with unresectable locally advanced NSCLC were enrolled between November 2019 and February 2021. Among the 28 evaluable cases, durvalumab was introduced in 24 (85.7%, 90% confidence interval: 70.2%–95.0%) of 28 patients after CRT, achieving the primary end point. All 29 patients who received IMRT completed the scheduled 60 Gy radiotherapy dose. One year of durvalumab treatment was completed in 12 of 24 patients (50%). In the 24 patients who were durvalumab-introduced, the median progression-free survival and overall survival were 20.9 (95% confidence interval: 6.9–not evaluable) months and not reached, respectively. Two-year progression-free survival and overall survival rates were 44% and 73%, respectively. Among the 29 patients in the safety analysis set, there were no treatment-related deaths or grade 4 nonhematological adverse events. Pneumonitis grade 1 was observed in 13 patients (45%), grade 2 in seven (24%), and grade 3 in one (3%).
Conclusions
High durvalumab introduction rate was reported after the completion of IMRT-adapted CRT under a prespecified radiation protocol. Its efficacy has been suggested, with favorable safety profiles, including a low incidence of severe pneumonitis.
Trial Registration
University Hospital Medical Information Network database ID: UMIN000038366
{"title":"Intensity-Modulated Radiotherapy for Locally Advanced Lung Cancer in the Immunotherapy Era: A Prospective Study WJOG12019L","authors":"Hideyuki Harada MD, PhD , Akito Hata MD , Masahiro Konno PhD , Nobuaki Mamesaya MD, PhD , Kiyoshi Nakamatsu MD, PhD , Koji Haratani MD, PhD , Takaya Yamamoto MD, PhD , Ryota Saito MD, PhD , Hiroshi Mayahara MD, PhD , Masaki Kokubo MD, PhD , Yuki Sato MD , Nobuki Imano MD, PhD , Takeshi Masuda PD, PhD , Haruyuki Fukuda MD, PhD , Toshikatsu Sado MD, PhD , Kenichi Yoshimura PhD , Yasumasa Nishimura MD, PhD , Kazuhiko Nakagawa MD, PhD , Isamu Okamoto MD, PhD , Nobuyuki Yamamoto MD, PhD","doi":"10.1016/j.jtocrr.2025.100828","DOIUrl":"10.1016/j.jtocrr.2025.100828","url":null,"abstract":"<div><h3>Introduction</h3><div>Chemoradiotherapy (CRT) followed by durvalumab is the standard of care for unresectable locally advanced NSCLC. Limited prospective data have been reported on intensity-modulated radiotherapy (IMRT)–adapted CRT in the immunotherapy era.</div></div><div><h3>Methods</h3><div>In this multicenter prospective observational study, patients underwent IMRT-adapted CRT (platinum-doublet chemotherapy plus 60 Gy IMRT in 30 fractions under a prespecified radiation protocol), followed by consolidative durvalumab. The primary outcome was the durvalumab introduction rate within 42 days post-CRT.</div></div><div><h3>Results</h3><div>Thirty-two patients with unresectable locally advanced NSCLC were enrolled between November 2019 and February 2021. Among the 28 evaluable cases, durvalumab was introduced in 24 (85.7%, 90% confidence interval: 70.2%–95.0%) of 28 patients after CRT, achieving the primary end point. All 29 patients who received IMRT completed the scheduled 60 Gy radiotherapy dose. One year of durvalumab treatment was completed in 12 of 24 patients (50%). In the 24 patients who were durvalumab-introduced, the median progression-free survival and overall survival were 20.9 (95% confidence interval: 6.9–not evaluable) months and not reached, respectively. Two-year progression-free survival and overall survival rates were 44% and 73%, respectively. Among the 29 patients in the safety analysis set, there were no treatment-related deaths or grade 4 nonhematological adverse events. Pneumonitis grade 1 was observed in 13 patients (45%), grade 2 in seven (24%), and grade 3 in one (3%).</div></div><div><h3>Conclusions</h3><div>High durvalumab introduction rate was reported after the completion of IMRT-adapted CRT under a prespecified radiation protocol. Its efficacy has been suggested, with favorable safety profiles, including a low incidence of severe pneumonitis.</div></div><div><h3>Trial Registration</h3><div>University Hospital Medical Information Network database ID: UMIN000038366</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 6","pages":"Article 100828"},"PeriodicalIF":3.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-20DOI: 10.1016/j.jtocrr.2025.100827
Micah Tratt BA , Anshu Bandhlish MD , Keith D. Eaton MD, PhD , Ted Gooley PhD , Nicholas Giustini MD , Lei Deng MD
Introduction
Lung adenocarcinoma (LUAD) with intestinal differentiation (LAID) comprises a rare and heterogeneous NSCLC of invasive mucinous, enteric, and colloid characteristics. In the era of chemotherapy, LAID was associated with a poorer prognosis compared with other LUADs. Leveraging the National Cancer Database, we assessed survival outcomes of LAID in the era of immunotherapy.
Methods
The National Cancer Database was queried for stage IV adenocarcinoma cases diagnosed from 2016 to 2019. LAID was defined as invasive mucinous adenocarcinoma, colloid adenocarcinoma, or enteric adenocarcinoma. An unadjusted comparison of survival distributions was performed using a log-rank test and adjusted by Cox multivariable regression.
Results
A total of 40,516 patients were identified, of whom 855 had LAID and 39,661 had other LUAD. Among the cases of LAID, 593 were classified as colloid, 253 as mucinous, and nine as enteric. Patients with LAID had a higher risk of death compared with other LUAD subtypes, with a hazard ratio (HR) of 1.31 (95% confidence interval: 1.21–1.43) and a median survival of 9.19 months and 11.81 months, respectively. This was relatively consistent across all treatment subgroups (HR = 1.40: immunotherapy alone, HR = 1.29: chemoimmunotherapy; HR = 1.25: chemotherapy alone). Patients with LAID treated with chemoimmunotherapy had a median overall survival of 11.16 months, 9.19 months when treated with immunotherapy alone, and 7.09 months when treated with chemotherapy alone.
Conclusions
Compared with other LUADs, LAID remains associated with poorer survival in the era of immunotherapy. Nevertheless, exposure to immunotherapy may be associated with improved survival compared with chemotherapy alone in this rare subgroup.
{"title":"Survival Outcomes of Lung Adenocarcinoma With Intestinal Differentiation in the Era of Immunotherapy","authors":"Micah Tratt BA , Anshu Bandhlish MD , Keith D. Eaton MD, PhD , Ted Gooley PhD , Nicholas Giustini MD , Lei Deng MD","doi":"10.1016/j.jtocrr.2025.100827","DOIUrl":"10.1016/j.jtocrr.2025.100827","url":null,"abstract":"<div><h3>Introduction</h3><div>Lung adenocarcinoma (LUAD) with intestinal differentiation (LAID) comprises a rare and heterogeneous NSCLC of invasive mucinous, enteric, and colloid characteristics. In the era of chemotherapy, LAID was associated with a poorer prognosis compared with other LUADs. Leveraging the National Cancer Database, we assessed survival outcomes of LAID in the era of immunotherapy.</div></div><div><h3>Methods</h3><div>The National Cancer Database was queried for stage IV adenocarcinoma cases diagnosed from 2016 to 2019. LAID was defined as invasive mucinous adenocarcinoma, colloid adenocarcinoma, or enteric adenocarcinoma. An unadjusted comparison of survival distributions was performed using a log-rank test and adjusted by Cox multivariable regression.</div></div><div><h3>Results</h3><div>A total of 40,516 patients were identified, of whom 855 had LAID and 39,661 had other LUAD. Among the cases of LAID, 593 were classified as colloid, 253 as mucinous, and nine as enteric. Patients with LAID had a higher risk of death compared with other LUAD subtypes, with a hazard ratio (HR) of 1.31 (95% confidence interval: 1.21–1.43) and a median survival of 9.19 months and 11.81 months, respectively. This was relatively consistent across all treatment subgroups (HR = 1.40: immunotherapy alone, HR = 1.29: chemoimmunotherapy; HR = 1.25: chemotherapy alone). Patients with LAID treated with chemoimmunotherapy had a median overall survival of 11.16 months, 9.19 months when treated with immunotherapy alone, and 7.09 months when treated with chemotherapy alone.</div></div><div><h3>Conclusions</h3><div>Compared with other LUADs, LAID remains associated with poorer survival in the era of immunotherapy. Nevertheless, exposure to immunotherapy may be associated with improved survival compared with chemotherapy alone in this rare subgroup.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 7","pages":"Article 100827"},"PeriodicalIF":3.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-19DOI: 10.1016/j.jtocrr.2025.100829
Anne C. Chiang MD, PhD , Russell W. Madison MS , Zoe June Assaf PhD , Alexander Fine PhD , Yi Cao PhD , Ole Gjoerup PhD , Yanmei Huang PhD , Dexter X. Jin PhD , Jason Hughes PhD , Vladan Antic MD, PhD , Amanda Young PhD , David Fabrizio MS , David Shames PhD , Sophia Maund PhD , Alexia Exarchos MPH , Shailendra Lakhanpal MD , Richard Zuniga MD , Lincoln W. Pasquina PhD , Katja Schulze PhD
Introduction
Circulating tumor DNA (ctDNA) monitoring is emerging as a minimally invasive complement to tumor imaging. We evaluated the validity of tissue-agnostic ctDNA quantification across four treatment modalities in NSCLC and SCLC.
Methods
Data from consenting patients were collected from electronic health records as part of the Prospective Clinico-Genomic study (NCT04180176). ctDNA tumor fraction (TF) was retrospectively calculated for plasma collected six to 15 weeks after therapy initiation. TF dynamics were compared among an exploratory cohort, NSCLC and SCLC validity cohorts, and by therapy class.
Results
In on-treatment plasma, undetectable TF was associated with longer real-world progression-free survival and real-world overall survival in exploratory (21.8 versus 8.8 mo; hazard ratio [HR] = 0.35, 95% confidence interval [CI]: 0.24–0.50), validity NSCLC (23.5 versus 9.5 mo; HR = 0.34, 95% CI: 0.22–0.53), and validity SCLC (15.9 versus 8.3 mo; HR = 0.19, 95% CI: 0.08–0.42) cohorts. Equal to or greater than 90% and equal to or greater than 50% TF reduction from baseline was also associated with significantly improved outcomes. ctDNA dynamics differed by treatment class: TF reported greater discriminatory power for selecting tumor responses to immunotherapy and targeted therapy (≥50% decrease in 91% of responders versus 24% of nonresponders) than chemotherapy and chemo-immunotherapy (86% versus 60%). TF dynamics correlated with outcomes, but models of real-world progression-free survival and real-world overall survival were improved when tumor response was included.
Conclusions
Tissue-agnostic monitoring of molecular response on the basis of ctDNA TF dynamics has utility in the real-world setting across four different treatment regimens. These results suggest that ctDNA dynamics may be complementary to tumor imaging in both NSCLC and SCLC to better inform patient care.
{"title":"Real-World Validity of Tissue-Agnostic Circulating Tumor DNA Response Monitoring in Lung Cancers Treated With Chemotherapy, Immunotherapy, or Targeted Agents","authors":"Anne C. Chiang MD, PhD , Russell W. Madison MS , Zoe June Assaf PhD , Alexander Fine PhD , Yi Cao PhD , Ole Gjoerup PhD , Yanmei Huang PhD , Dexter X. Jin PhD , Jason Hughes PhD , Vladan Antic MD, PhD , Amanda Young PhD , David Fabrizio MS , David Shames PhD , Sophia Maund PhD , Alexia Exarchos MPH , Shailendra Lakhanpal MD , Richard Zuniga MD , Lincoln W. Pasquina PhD , Katja Schulze PhD","doi":"10.1016/j.jtocrr.2025.100829","DOIUrl":"10.1016/j.jtocrr.2025.100829","url":null,"abstract":"<div><h3>Introduction</h3><div>Circulating tumor DNA (ctDNA) monitoring is emerging as a minimally invasive complement to tumor imaging. We evaluated the validity of tissue-agnostic ctDNA quantification across four treatment modalities in NSCLC and SCLC.</div></div><div><h3>Methods</h3><div>Data from consenting patients were collected from electronic health records as part of the Prospective Clinico-Genomic study (NCT04180176). ctDNA tumor fraction (TF) was retrospectively calculated for plasma collected six to 15 weeks after therapy initiation. TF dynamics were compared among an exploratory cohort, NSCLC and SCLC validity cohorts, and by therapy class.</div></div><div><h3>Results</h3><div>In on-treatment plasma, undetectable TF was associated with longer real-world progression-free survival and real-world overall survival in exploratory (21.8 versus 8.8 mo; hazard ratio [HR] = 0.35, 95% confidence interval [CI]: 0.24–0.50), validity NSCLC (23.5 versus 9.5 mo; HR = 0.34, 95% CI: 0.22–0.53), and validity SCLC (15.9 versus 8.3 mo; HR = 0.19, 95% CI: 0.08–0.42) cohorts. Equal to or greater than 90% and equal to or greater than 50% TF reduction from baseline was also associated with significantly improved outcomes. ctDNA dynamics differed by treatment class: TF reported greater discriminatory power for selecting tumor responses to immunotherapy and targeted therapy (≥50% decrease in 91% of responders versus 24% of nonresponders) than chemotherapy and chemo-immunotherapy (86% versus 60%). TF dynamics correlated with outcomes, but models of real-world progression-free survival and real-world overall survival were improved when tumor response was included.</div></div><div><h3>Conclusions</h3><div>Tissue-agnostic monitoring of molecular response on the basis of ctDNA TF dynamics has utility in the real-world setting across four different treatment regimens. These results suggest that ctDNA dynamics may be complementary to tumor imaging in both NSCLC and SCLC to better inform patient care.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 9","pages":"Article 100829"},"PeriodicalIF":3.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-13DOI: 10.1016/j.jtocrr.2025.100824
Cheol-Kyu Park MD, PhD , Maryam Khalil BSc , Nhu-An Pham PhD , Stephanie Wong BSc , Dalam Ly PhD , Adrian Sacher MD, FRCPC , Ming-Sound Tsao MD, FRCPC
{"title":"Corrigendum to ‘Humanized Mouse Models for Immuno-Oncology Research: A Review and Implications in Lung Cancer Research’ [JTO Clinical and Research Reports Volume 6 Issue 3 (2025) 100781]","authors":"Cheol-Kyu Park MD, PhD , Maryam Khalil BSc , Nhu-An Pham PhD , Stephanie Wong BSc , Dalam Ly PhD , Adrian Sacher MD, FRCPC , Ming-Sound Tsao MD, FRCPC","doi":"10.1016/j.jtocrr.2025.100824","DOIUrl":"10.1016/j.jtocrr.2025.100824","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 5","pages":"Article 100824"},"PeriodicalIF":3.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705770","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}
Pub Date : 2025-03-10DOI: 10.1016/j.jtocrr.2025.100823
Margaret Stalker MD , Suzanne L. Walker PhD, CRNP, AOCN, BC , Emily Lebow MD , Emily Ling-Lin Pai MD, PhD , Alex Watts MS , Wei-Ting Hwang PhD , Amir Banihashemi MD , Evan Anderson MSN , Leonid Roshkovan MD , Sharyn I. Katz MD , Leslie Litzky MD , Andrew R. Haas MD, PhD , Sunil Singhal MD , Corey J. Langer MD , Keith Cengel MD, PhD , Melina E. Marmarelis MD, MSCE
Introduction
Immunotherapy (IO) has reported efficacy in pleural mesothelioma (PM). Brain metastases (BMs) in PM are rare; thus, surveillance brain imaging is not included in the guidelines. We evaluated the incidence of BM by treatment type.
Methods
In this retrospective analysis, patients with PM treated at the University of Pennsylvania between January 1, 2015, and August 31, 2023, were included. Demographic and clinical data were extracted from the medical records. The treatment categories included chemotherapy, single-agent IO, and dual-agent IO. A two-tailed Z score was used to determine a difference in the proportion of BM. Overall survival (OS) was analyzed using the Kaplan-Meier method. Of those with BM, available brain tissue was further analyzed.
Results
In total, 251 patients were included; the median age of the participants was 73 years (range: 35–92 y), 79% were male individuals, 91% were white, and 73% had epithelioid histology. In the study, 102 (40.6%) were treated with chemotherapy, 100 (39.8%) with single-agent IO, and 49 (19.5%) with dual-agent IO. The median OS (mOS) was 21.6 months (95% confidence interval: 17.7–25.5) and did not differ between treatment groups (p = 0.774). A higher proportion of patients treated with IO developed BM than those treated with chemotherapy (6/149 [4%] versus 0/102 [0%]; Z score p = 0.04). The mOS from BM diagnosis was 95 days (range: 16–1025 d). The histomorphology of three patients with available brain tissue were similar to the primary site and reported substantial edema and hemorrhage.
Conclusions
In this retrospective study, clinically significant BM was most prevalent in those exposed to IO and not seen in those receiving chemotherapy despite similar mOS between the groups. Brain imaging should be considered before starting IO in patients with PM.
{"title":"Incidence and Outcomes of Brain Metastasis in Pleural Mesothelioma in the Era of Immunotherapy","authors":"Margaret Stalker MD , Suzanne L. Walker PhD, CRNP, AOCN, BC , Emily Lebow MD , Emily Ling-Lin Pai MD, PhD , Alex Watts MS , Wei-Ting Hwang PhD , Amir Banihashemi MD , Evan Anderson MSN , Leonid Roshkovan MD , Sharyn I. Katz MD , Leslie Litzky MD , Andrew R. Haas MD, PhD , Sunil Singhal MD , Corey J. Langer MD , Keith Cengel MD, PhD , Melina E. Marmarelis MD, MSCE","doi":"10.1016/j.jtocrr.2025.100823","DOIUrl":"10.1016/j.jtocrr.2025.100823","url":null,"abstract":"<div><h3>Introduction</h3><div>Immunotherapy (IO) has reported efficacy in pleural mesothelioma (PM). Brain metastases (BMs) in PM are rare; thus, surveillance brain imaging is not included in the guidelines. We evaluated the incidence of BM by treatment type.</div></div><div><h3>Methods</h3><div>In this retrospective analysis, patients with PM treated at the University of Pennsylvania between January 1, 2015, and August 31, 2023, were included. Demographic and clinical data were extracted from the medical records. The treatment categories included chemotherapy, single-agent IO, and dual-agent IO. A two-tailed Z score was used to determine a difference in the proportion of BM. Overall survival (OS) was analyzed using the Kaplan-Meier method. Of those with BM, available brain tissue was further analyzed.</div></div><div><h3>Results</h3><div>In total, 251 patients were included; the median age of the participants was 73 years (range: 35–92 y), 79% were male individuals, 91% were white, and 73% had epithelioid histology. In the study, 102 (40.6%) were treated with chemotherapy, 100 (39.8%) with single-agent IO, and 49 (19.5%) with dual-agent IO. The median OS (mOS) was 21.6 months (95% confidence interval: 17.7–25.5) and did not differ between treatment groups (<em>p</em> = 0.774). A higher proportion of patients treated with IO developed BM than those treated with chemotherapy (6/149 [4%] versus 0/102 [0%]; Z score <em>p</em> = 0.04). The mOS from BM diagnosis was 95 days (range: 16–1025 d). The histomorphology of three patients with available brain tissue were similar to the primary site and reported substantial edema and hemorrhage.</div></div><div><h3>Conclusions</h3><div>In this retrospective study, clinically significant BM was most prevalent in those exposed to IO and not seen in those receiving chemotherapy despite similar mOS between the groups. Brain imaging should be considered before starting IO in patients with PM.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 5","pages":"Article 100823"},"PeriodicalIF":3.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791223","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}
Pub Date : 2025-03-08DOI: 10.1016/j.jtocrr.2025.100822
Marcello Moro Queiroz MD , Ricardo Dahmer Tiecher MD , João Felipe Lima Feldmann MD , Elisangela Monteiro Coser BSc , Mariana Vargas Cruz PhD , Livia Loureiro PhD , Gabriela Franco Katz MD , Marina Henkin Behar MD , João Victor Machado Alessi MD , Leonardo de Abreu Testagrossa PhD , Anamaria Aranha Camargo PhD , Paula Fontes Asprino PhD , Fabiana Bettoni PhD , Artur Katz MD
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by ectopic fibroblast growth factor-23 (FGF23) production. We report a unique case of a 78-year-old female patient with refractory hypophosphatemia, ultimately diagnosed as TIO, in the context of two metastatic primary lung cancers: adenocarcinoma and SCLC. Molecular analyses of tumor samples highlighted FGF23 amplification in one adenocarcinoma sample and FGF23 deletion in one SCLC sample, suggesting a potential link between tumor FGF23 molecular alterations and elevated serum FGF23 levels. This case underscores the complexity of diagnoses and management of TIO when associated with solid tumors and highlights the need for awareness of this condition to prevent diagnostic delays. Future research should explore the mechanisms linking FGF23 alterations and cancer progression and evaluate targeted therapies for TIO in the context of resistant metastatic cancers.
{"title":"Tumor-Induced Osteomalacia in a Patient With FGF23-Amplified Lung Adenocarcinoma and FGF23-Deleted SCLC: Case Report","authors":"Marcello Moro Queiroz MD , Ricardo Dahmer Tiecher MD , João Felipe Lima Feldmann MD , Elisangela Monteiro Coser BSc , Mariana Vargas Cruz PhD , Livia Loureiro PhD , Gabriela Franco Katz MD , Marina Henkin Behar MD , João Victor Machado Alessi MD , Leonardo de Abreu Testagrossa PhD , Anamaria Aranha Camargo PhD , Paula Fontes Asprino PhD , Fabiana Bettoni PhD , Artur Katz MD","doi":"10.1016/j.jtocrr.2025.100822","DOIUrl":"10.1016/j.jtocrr.2025.100822","url":null,"abstract":"<div><div>Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by ectopic fibroblast growth factor-23 (FGF23) production. We report a unique case of a 78-year-old female patient with refractory hypophosphatemia, ultimately diagnosed as TIO, in the context of two metastatic primary lung cancers: adenocarcinoma and SCLC. Molecular analyses of tumor samples highlighted <em>FGF23</em> amplification in one adenocarcinoma sample and <em>FGF23</em> deletion in one SCLC sample, suggesting a potential link between tumor <em>FGF23</em> molecular alterations and elevated serum FGF23 levels. This case underscores the complexity of diagnoses and management of TIO when associated with solid tumors and highlights the need for awareness of this condition to prevent diagnostic delays. Future research should explore the mechanisms linking <em>FGF23</em> alterations and cancer progression and evaluate targeted therapies for TIO in the context of resistant metastatic cancers.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 6","pages":"Article 100822"},"PeriodicalIF":3.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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