Pub Date : 2025-06-28DOI: 10.1016/j.jtocrr.2025.100871
Sun Min Lim MD, PhD , Joo Sung Gabriel Shim MD , Hyo Sup Shim MD, PhD , Junko Tanizaki MD, PhD , Jorn Nutzinger MD , Byoung Chul Cho MD, PhD , Ross A. Soo MBBS, PhD
SCLC is a high-grade neuroendocrine malignancy associated with poor prognosis, comprising 15% of lung cancer cases globally. Advances in genetic profiling have revealed that SCLC is a molecularly heterogeneous disease, categorized into subtypes such as SCLC-A, SCLC-N, SCLC-P, and SCLC-I, on the basis of their neuroendocrine and immune-related characteristics. This heterogeneity underscores the need for tailored therapeutic strategies.
Large cell neuroendocrine carcinoma (LCNEC) shares histologic and molecular similarities with SCLC but remains a distinct entity. LCNEC is categorized into two major subtypes: Type I, characterized by STK11 and KEAP1 mutations and a neuroendocrine phenotype, and Type II, defined by TP53 and RB1 alterations with higher proliferative indices. LCNEC's rarity and molecular diversity present challenges for standardized treatment, further highlighting the need for comparative research with SCLC.
In this review, we highlight the genetic and clinicopathologic features of SCLC and LCNEC. Furthermore, we discuss emerging therapeutics and future directions in the treatment of SCLC and LCNEC.
{"title":"What Is On the Horizon for the Diagnosis and Treatment of SCLC and Large Cell Neuroendocrine Cancer?","authors":"Sun Min Lim MD, PhD , Joo Sung Gabriel Shim MD , Hyo Sup Shim MD, PhD , Junko Tanizaki MD, PhD , Jorn Nutzinger MD , Byoung Chul Cho MD, PhD , Ross A. Soo MBBS, PhD","doi":"10.1016/j.jtocrr.2025.100871","DOIUrl":"10.1016/j.jtocrr.2025.100871","url":null,"abstract":"<div><div>SCLC is a high-grade neuroendocrine malignancy associated with poor prognosis, comprising 15% of lung cancer cases globally. Advances in genetic profiling have revealed that SCLC is a molecularly heterogeneous disease, categorized into subtypes such as SCLC-A, SCLC-N, SCLC-P, and SCLC-I, on the basis of their neuroendocrine and immune-related characteristics. This heterogeneity underscores the need for tailored therapeutic strategies.</div><div>Large cell neuroendocrine carcinoma (LCNEC) shares histologic and molecular similarities with SCLC but remains a distinct entity. LCNEC is categorized into two major subtypes: Type I, characterized by <em>STK11</em> and <em>KEAP1</em> mutations and a neuroendocrine phenotype, and Type II, defined by <em>TP53</em> and <em>RB1</em> alterations with higher proliferative indices. LCNEC's rarity and molecular diversity present challenges for standardized treatment, further highlighting the need for comparative research with SCLC.</div><div>In this review, we highlight the genetic and clinicopathologic features of SCLC and LCNEC. Furthermore, we discuss emerging therapeutics and future directions in the treatment of SCLC and LCNEC.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 9","pages":"Article 100871"},"PeriodicalIF":3.5,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144780077","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}
Lenvatinib, an orally administered multitargeted kinase inhibitor, has exhibited antitumor activity against several cancer types, including thymic carcinomas. Although “disease flare” (a rapid worsening of the tumor on the discontinuation of lenvatinib) has been reported, such cases are rare in thymic carcinoma. Understanding this phenomenon is clinically significant, as it may cause rapid deterioration requiring urgent therapeutic intervention and patient death. This retrospective study aimed to determine the frequency and characteristics of disease flares in patients with thymic carcinoma.
Methods
We retrospectively reviewed the records of patients with thymic carcinoma who received lenvatinib between January 2018 and March 2024 at the National Cancer Center Hospital in Tokyo, Japan. Patients were categorized into flare and nonflare groups, with their characteristics, clinical outcomes, and genetic profiles compared.
Results
Of the 52 patients, four patients (8%) experienced disease flares after lenvatinib failure. Baseline characteristics according to the presence of disease flares after discontinuation revealed no significant differences. All four patients experienced increased pleural effusions within 1 week of lenvatinib discontinuation. Progression-free survival (p = 0.307) or objective response rates (p = 0.257) did not differ significantly between the flare and nonflare groups regarding lenvatinib treatment efficacy. Similarly, 24 of the 52 patients underwent comprehensive genomic profiling using next-generation sequencing platforms and RNA sequencing. In the flare group, KIT mutations occurred in 50% of patients, with KMT2C mutations being significantly more common (p = 0.022).
Conclusions
The discontinuation of lenvatinib in patients with thymic carcinoma caused disease flare in 8% of cases, with KMT2C and KIT mutations emerging as potential contributing factors. These findings suggest that molecular profiling helps in identifying patients at high risk of disease flare and informs future treatment sequencing strategies.
{"title":"Genetic Characteristics of Disease Flare After Lenvatinib Discontinuation in Patients With Thymic Carcinoma: A Brief Report","authors":"Tomoaki Nakamura MD , Tatsuya Yoshida MD, PhD , Ken Masuda MD , Jun Sato MD, PhD , Yuki Shinno MD, PhD , Yuji Matsumoto MD, PhD , Yusuke Okuma MD, PhD , Yasushi Goto MD, PhD , Hidehito Horinouchi MD, PhD , Noboru Yamamoto MD, PhD , Yuichiro Ohe MD, PhD","doi":"10.1016/j.jtocrr.2025.100872","DOIUrl":"10.1016/j.jtocrr.2025.100872","url":null,"abstract":"<div><h3>Introduction</h3><div>Lenvatinib, an orally administered multitargeted kinase inhibitor, has exhibited antitumor activity against several cancer types, including thymic carcinomas. Although “disease flare” (a rapid worsening of the tumor on the discontinuation of lenvatinib) has been reported, such cases are rare in thymic carcinoma. Understanding this phenomenon is clinically significant, as it may cause rapid deterioration requiring urgent therapeutic intervention and patient death. This retrospective study aimed to determine the frequency and characteristics of disease flares in patients with thymic carcinoma.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed the records of patients with thymic carcinoma who received lenvatinib between January 2018 and March 2024 at the National Cancer Center Hospital in Tokyo, Japan. Patients were categorized into flare and nonflare groups, with their characteristics, clinical outcomes, and genetic profiles compared.</div></div><div><h3>Results</h3><div>Of the 52 patients, four patients (8%) experienced disease flares after lenvatinib failure. Baseline characteristics according to the presence of disease flares after discontinuation revealed no significant differences. All four patients experienced increased pleural effusions within 1 week of lenvatinib discontinuation. Progression-free survival (<em>p</em> = 0.307) or objective response rates (<em>p</em> = 0.257) did not differ significantly between the flare and nonflare groups regarding lenvatinib treatment efficacy. Similarly, 24 of the 52 patients underwent comprehensive genomic profiling using next-generation sequencing platforms and RNA sequencing. In the flare group, <em>KIT</em> mutations occurred in 50% of patients, with <em>KMT2C</em> mutations being significantly more common (<em>p</em> = 0.022).</div></div><div><h3>Conclusions</h3><div>The discontinuation of lenvatinib in patients with thymic carcinoma caused disease flare in 8% of cases, with <em>KMT2C</em> and <em>KIT</em> mutations emerging as potential contributing factors. These findings suggest that molecular profiling helps in identifying patients at high risk of disease flare and informs future treatment sequencing strategies.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 12","pages":"Article 100872"},"PeriodicalIF":3.5,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145469060","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 : 2025-06-20DOI: 10.1016/j.jtocrr.2025.100868
Koichi Goto MD, PhD , Herbert H. Loong M.B.B.S. , Caicun Zhou MD, PhD , Kazumi Nishino MD, PhD , Dae Ho Lee MD, PhD , Se-Hoon Lee MD , James Chih-Hsin Yang MD, PhD , Dan Liu PhD , Minji Kim Uh PhD , Hongmei Han MS, MAS , Tarun Puri MD , Aimee Bence Lin PhD , Ying Cheng MD
Introduction
Selpercatinib’s consistent efficacy and manageable safety profile were observed in patients with RET fusion–positive NSCLC across geographies in single-arm studies (LIBRETTO-001 and LIBRETTO-321). Here, we report the efficacy and safety of the phase 3 study LIBRETTO-431 in patients from East Asia.
Methods
LIBRETTO-431 (NCT04194944) is a randomized, open-label phase 3 trial comparing first-line selpercatinib versus pemetrexed and platinum with or without pembrolizumab. Geography (East Asia versus non-East Asia) was a stratification factor. Efficacy end points including progression-free survival (PFS), objective response rate, and duration of response as assessed by means of blinded independent central review were evaluated in patients from East Asia. Pharmacokinetics were assessed in the selpercatinib group. Safety data were collected for all patients who received at least one dose of study treatment.
Results
Of the 261 patients enrolled, 142 (54.4%) were from East Asia, with 116 randomized to the intention-to-treat-pembrolizumab population (selpercatinib: n = 75, control: n = 41). With a median follow-up of 19.4 and 21.2 months in the selpercatinib and control groups respectively, the median PFS in patients from East Asia was not yet reached for selpercatinib (95% confidence interval (CI): 16.4–not evaluable) versus 11.1 months (95% CI: 7.0–16.8) for control (hazard ratio: 0.38 [95%CI: 0.22–0.68]; p = 0.0008). Safety and pharmacokinetics were consistent with those previously reported across the development program and adverse events were generally manageable with dose adjustments.
Conclusions
Consistent with results in the overall LIBRETTO-431 population, selpercatinib exhibited superior PFS compared with chemotherapy plus pembrolizumab in patients from East Asia with a manageable safety profile. These data further highlight the importance of early comprehensive genomic testing and the use of selpercatinib as a preferred first-line regimen in patients with RET fusion–positive NSCLC across geographies.
在单臂研究（LIBRETTO-001和LIBRETTO-321）中，selpercatinib在不同地区的RET融合阳性NSCLC患者中具有一致的疗效和可管理的安全性。在此，我们报告了3期研究LIBRETTO-431在东亚患者中的有效性和安全性。方法：slibretto -431 （NCT04194944）是一项随机、开放标签的3期试验，比较了一线selpercatinib与培美曲塞和铂在使用或不使用派姆单抗时的疗效。地理（东亚与非东亚）是一个分层因素。疗效终点包括无进展生存期（PFS）、客观缓解率和持续时间，通过盲法独立中心评价在东亚患者中进行评估。观察自泊替尼组的药代动力学。收集了所有接受至少一剂研究治疗的患者的安全性数据。在纳入的261例患者中，142例（54.4%）来自东亚，其中116例随机分配到意向治疗派姆单抗人群（selpercatinib: n = 75，对照组：n = 41）。selpercatinib组和对照组的中位随访时间分别为19.4和21.2个月，selpercatinib组东亚患者的中位PFS尚未达到（95%置信区间（CI）： 16.4 -不可评估），而对照组的中位PFS为11.1个月（95% CI: 7.0-16.8）（风险比：0.38 [95%CI: 0.22-0.68]; p = 0.0008）。安全性和药代动力学与先前在整个开发项目中报道的一致，不良事件通常可以通过剂量调整来控制。与LIBRETTO-431总体人群的结果一致，selpercatinib在东亚患者中与化疗加派姆单抗相比表现出更高的PFS，并且具有可控的安全性。这些数据进一步强调了早期全面基因组检测的重要性，以及将selpercatinib作为RET融合阳性NSCLC患者首选一线治疗方案的重要性。
{"title":"First-line Selpercatinib or Chemotherapy and Pembrolizumab in Patients From East Asia With RET Fusion–Positive NSCLC: A LIBRETTO-431 Subgroup Analysis","authors":"Koichi Goto MD, PhD , Herbert H. Loong M.B.B.S. , Caicun Zhou MD, PhD , Kazumi Nishino MD, PhD , Dae Ho Lee MD, PhD , Se-Hoon Lee MD , James Chih-Hsin Yang MD, PhD , Dan Liu PhD , Minji Kim Uh PhD , Hongmei Han MS, MAS , Tarun Puri MD , Aimee Bence Lin PhD , Ying Cheng MD","doi":"10.1016/j.jtocrr.2025.100868","DOIUrl":"10.1016/j.jtocrr.2025.100868","url":null,"abstract":"<div><h3>Introduction</h3><div>Selpercatinib’s consistent efficacy and manageable safety profile were observed in patients with <em>RET</em> fusion–positive NSCLC across geographies in single-arm studies (LIBRETTO-001 and LIBRETTO-321). Here, we report the efficacy and safety of the phase 3 study LIBRETTO-431 in patients from East Asia.</div></div><div><h3>Methods</h3><div>LIBRETTO-431 (NCT04194944) is a randomized, open-label phase 3 trial comparing first-line selpercatinib versus pemetrexed and platinum with or without pembrolizumab. Geography (East Asia versus non-East Asia) was a stratification factor. Efficacy end points including progression-free survival (PFS), objective response rate, and duration of response as assessed by means of blinded independent central review were evaluated in patients from East Asia. Pharmacokinetics were assessed in the selpercatinib group. Safety data were collected for all patients who received at least one dose of study treatment.</div></div><div><h3>Results</h3><div>Of the 261 patients enrolled, 142 (54.4%) were from East Asia, with 116 randomized to the intention-to-treat-pembrolizumab population (selpercatinib: n = 75, control: n = 41). With a median follow-up of 19.4 and 21.2 months in the selpercatinib and control groups respectively, the median PFS in patients from East Asia was not yet reached for selpercatinib (95% confidence interval (CI): 16.4–not evaluable) versus 11.1 months (95% CI: 7.0–16.8) for control (hazard ratio: 0.38 [95%CI: 0.22–0.68]; <em>p</em> = 0.0008). Safety and pharmacokinetics were consistent with those previously reported across the development program and adverse events were generally manageable with dose adjustments.</div></div><div><h3>Conclusions</h3><div>Consistent with results in the overall LIBRETTO-431 population, selpercatinib exhibited superior PFS compared with chemotherapy plus pembrolizumab in patients from East Asia with a manageable safety profile. These data further highlight the importance of early comprehensive genomic testing and the use of selpercatinib as a preferred first-line regimen in patients with <em>RET</em> fusion–positive NSCLC across geographies.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100868"},"PeriodicalIF":3.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933603","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 : 2025-06-19DOI: 10.1016/j.jtocrr.2025.100869
Kirstin Perdrizet MD , Lisa W. Le MSc , Anthea Lau BSc , Xiaochen Tai MSc , Mary R. Rabey BMBS , Jennifer H. Law MSc , Donna Maziak MD , Natasha Leighl MD
Introduction
The coronavirus disease 2019 pandemic disrupted cancer care delivery globally, with many jurisdictions reporting reductions in lung cancer diagnoses and delays in treatment. In Ontario, Canada, both institutional and provincial data have reported mixed trends in NSCLC presentation and care. This study aimed to assess the short-term impact of the coronavirus disease 2019 pandemic on NSCLC diagnoses and treatment pathways across Ontario using population-level data from Cancer Care Ontario administrative health databases.
Methods
We conducted a retrospective cohort study of patients diagnosed with NSCLC in Ontario between January 1, 2019 and December 31, 2020. The cohort was created using relevant diagnostic codes and linked provincial databases to evaluate diagnostic trends and access to surgical, medical, and radiation oncology services. Statistical analyses included Poisson regression to assess changes in diagnosis rates and multivariable linear regressions to evaluate wait times, adjusting for age, sex, income quintile, and geographic region.
Results
A total of 13,407 NSCLC cases were identified. There was a 6% overall decline in diagnoses in 2020, with a 31% drop during quarter 2 (April–June 2020). The mean wait times for surgical consultation and treatment and also medical and radiation oncology consults improved or remained stable. No delays were found in systemic therapy initiation. Multivariable analyses confirmed these findings.
Conclusions
NSCLC care delivery in Ontario remained stable during the early pandemic period. Declines in diagnosis warrant further investigation using longer-term data. Real-time data systems are essential for future pandemic preparedness and response.
{"title":"Impact of the COVID-19 Pandemic on Diagnosis and Multidisciplinary Treatment of NSCLC in Ontario, Canada","authors":"Kirstin Perdrizet MD , Lisa W. Le MSc , Anthea Lau BSc , Xiaochen Tai MSc , Mary R. Rabey BMBS , Jennifer H. Law MSc , Donna Maziak MD , Natasha Leighl MD","doi":"10.1016/j.jtocrr.2025.100869","DOIUrl":"10.1016/j.jtocrr.2025.100869","url":null,"abstract":"<div><h3>Introduction</h3><div>The coronavirus disease 2019 pandemic disrupted cancer care delivery globally, with many jurisdictions reporting reductions in lung cancer diagnoses and delays in treatment. In Ontario, Canada, both institutional and provincial data have reported mixed trends in NSCLC presentation and care. This study aimed to assess the short-term impact of the coronavirus disease 2019 pandemic on NSCLC diagnoses and treatment pathways across Ontario using population-level data from Cancer Care Ontario administrative health databases.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study of patients diagnosed with NSCLC in Ontario between January 1, 2019 and December 31, 2020. The cohort was created using relevant diagnostic codes and linked provincial databases to evaluate diagnostic trends and access to surgical, medical, and radiation oncology services. Statistical analyses included Poisson regression to assess changes in diagnosis rates and multivariable linear regressions to evaluate wait times, adjusting for age, sex, income quintile, and geographic region.</div></div><div><h3>Results</h3><div>A total of 13,407 NSCLC cases were identified. There was a 6% overall decline in diagnoses in 2020, with a 31% drop during quarter 2 (April–June 2020). The mean wait times for surgical consultation and treatment and also medical and radiation oncology consults improved or remained stable. No delays were found in systemic therapy initiation. Multivariable analyses confirmed these findings.</div></div><div><h3>Conclusions</h3><div>NSCLC care delivery in Ontario remained stable during the early pandemic period. Declines in diagnosis warrant further investigation using longer-term data. Real-time data systems are essential for future pandemic preparedness and response.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 9","pages":"Article 100869"},"PeriodicalIF":3.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144830548","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}
Despite the efficacy of osimertinib in the first-line treatment of advanced EGFR-mutated NSCLC, the development of resistance is nearly inevitable. BRAF mutations and fusions are reported in 1% to 3% of patients with EGFR-mutated NSCLC receiving osimertinib and represent potential targetable alterations.
In this case report, we discuss the rationale for EGFR-MEK co-inhibition in a patient with EGFR-mutated NSCLC treated with osimertinib that developed a CTNNA1-BRAF fusion at progression. In addition, we provide a brief overview of the current evidence of BRAF fusions as an acquired resistance mechanism to osimertinib and potential treatment strategies.
{"title":"BRAF Fusion as Resistance Mechanism to Osimertinib in EGFR-Mutated NSCLC: A Case Report and Review of Literature","authors":"Marianna Peroni MD , Alessandro Leonetti MD, PhD , Roberta Minari MSc, PhD , Michela Verzè MSc , Letizia Gnetti MD , Lorena Bottarelli MSc, PhD , Cinzia Azzoni MSc, PhD , Marco Galaverni MD , Nicola Simoni MD , Gabriele Missale MD , Elisabetta Biasini MD , Marcello Tiseo MD, PhD","doi":"10.1016/j.jtocrr.2025.100867","DOIUrl":"10.1016/j.jtocrr.2025.100867","url":null,"abstract":"<div><div>Despite the efficacy of osimertinib in the first-line treatment of advanced <em>EGFR</em>-mutated NSCLC, the development of resistance is nearly inevitable. <em>BRAF</em> mutations and fusions are reported in 1% to 3% of patients with <em>EGFR</em>-mutated NSCLC receiving osimertinib and represent potential targetable alterations.</div><div>In this case report, we discuss the rationale for EGFR-MEK co-inhibition in a patient with <em>EGFR</em>-mutated NSCLC treated with osimertinib that developed a <em>CTNNA</em><em>1-BRAF</em> fusion at progression. In addition, we provide a brief overview of the current evidence of <em>BRAF</em> fusions as an acquired resistance mechanism to osimertinib and potential treatment strategies.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 8","pages":"Article 100867"},"PeriodicalIF":3.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144632070","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 : 2025-06-19DOI: 10.1016/j.jtocrr.2025.100866
Jay M. Lee MD , Alessandro Brunelli MD , Amy L. Cummings MD , Enriqueta Felip MD, PhD , Catherine A. Shu MD , Benjamin J. Solomon M.B.B.S., PhD , Masahiro Tsuboi MD , Heather Wakelee MD , Anjali Saqi MD , Yi-Long Wu MD , Pao-Chen Li PhD , Barbara J. Gitlitz MD
Phase 3 trials of neoadjuvant, perioperative, and adjuvant immune checkpoint inhibitors combined with chemotherapy (ICI-CT) in resectable early-stage NSCLC (eNSCLC) have reported that all three approaches confer an event-free or disease-free survival benefit over CT alone, with acceptable safety profiles. All three strategies are approved standards of care for eNSCLC. This review provides a detailed analysis of these phase 3 ICI-CT trials and addresses the considerations regarding the selection of each approach, including protocol schema and baseline patient and tumor differences, preoperative staging, surgical outcomes, efficacy end points, safety, treatment disposition, and the programmed death-ligand 1 (PD-L1) efficacy biomarker. The differences between regimens and study populations among these ICI-CT trials hamper cross-trial comparisons and highlight the need for head-to-head trials. Patients achieving pathologic complete response with neoadjuvant ICI-CT have better survival outcomes irrespective of subsequent treatment, but the optimal number of preoperative ICI-CT cycles needed to achieve pathologic complete response has not been defined. The choice between a neoadjuvant or perioperative versus adjuvant treatment approach involves a risk-benefit assessment of the potential for preoperative attrition to surgery, postoperative attrition to ICI-CT, and the anticipated toxicity profile. Current limitations of invasive lymph node staging mean that adjuvant ICI remains an important treatment strategy, but preoperative node staging is imperative. Future studies that identify the safety and toxicity contributions of each treatment phase in perioperative trials will confirm whether a pre- or postoperative ICI approach is superior, whether there is added benefit to adjuvant after neoadjuvant ICI-CT, and which patients will benefit the most from each approach.
{"title":"Phase 3 Trials of Neoadjuvant, Perioperative, and Adjuvant Chemoimmunotherapy for Resectable, Early-Stage NSCLC: Comprehensive Review and Detailed Analysis","authors":"Jay M. Lee MD , Alessandro Brunelli MD , Amy L. Cummings MD , Enriqueta Felip MD, PhD , Catherine A. Shu MD , Benjamin J. Solomon M.B.B.S., PhD , Masahiro Tsuboi MD , Heather Wakelee MD , Anjali Saqi MD , Yi-Long Wu MD , Pao-Chen Li PhD , Barbara J. Gitlitz MD","doi":"10.1016/j.jtocrr.2025.100866","DOIUrl":"10.1016/j.jtocrr.2025.100866","url":null,"abstract":"<div><div>Phase 3 trials of neoadjuvant, perioperative, and adjuvant immune checkpoint inhibitors combined with chemotherapy (ICI-CT) in resectable early-stage NSCLC (eNSCLC) have reported that all three approaches confer an event-free or disease-free survival benefit over CT alone, with acceptable safety profiles. All three strategies are approved standards of care for eNSCLC. This review provides a detailed analysis of these phase 3 ICI-CT trials and addresses the considerations regarding the selection of each approach, including protocol schema and baseline patient and tumor differences, preoperative staging, surgical outcomes, efficacy end points, safety, treatment disposition, and the programmed death-ligand 1 (PD-L1) efficacy biomarker. The differences between regimens and study populations among these ICI-CT trials hamper cross-trial comparisons and highlight the need for head-to-head trials. Patients achieving pathologic complete response with neoadjuvant ICI-CT have better survival outcomes irrespective of subsequent treatment, but the optimal number of preoperative ICI-CT cycles needed to achieve pathologic complete response has not been defined. The choice between a neoadjuvant or perioperative versus adjuvant treatment approach involves a risk-benefit assessment of the potential for preoperative attrition to surgery, postoperative attrition to ICI-CT, and the anticipated toxicity profile. Current limitations of invasive lymph node staging mean that adjuvant ICI remains an important treatment strategy, but preoperative node staging is imperative. Future studies that identify the safety and toxicity contributions of each treatment phase in perioperative trials will confirm whether a pre- or postoperative ICI approach is superior, whether there is added benefit to adjuvant after neoadjuvant ICI-CT, and which patients will benefit the most from each approach.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 9","pages":"Article 100866"},"PeriodicalIF":3.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725044","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 : 2025-06-13DOI: 10.1016/j.jtocrr.2025.100860
Herbert Ho-fung Loong MBBS, FRCP , Xuanqi Pan PhD , Carlos K.H. Wong PhD , Chao-Hua Chiu MD , Szu-Chun Yang MD , Matthew Shing Hin Chung BSc , Molly Siu Ching Li MBBS , Lisa de Jong PhD , Harry Groen MD, PhD , Maarten J. Postma PhD , Pan-Chyr Yang MD, PhD
Introduction
Lung cancer (LC) accounts for 26.4% of all cancer deaths in Hong Kong (HK). Lung cancer screening (LCS) with low-dose computed tomography (LDCT) can reduce LC mortality. The cost-effectiveness of LDCT screening in high-risk individuals on the basis of smoking history has previously been investigated. However, nearly half of patients with LC in HK never smoke, indicating a different LC epidemiology compared with Western countries, where most LC cases are associated with smoking. We conducted a cost-effectiveness analysis for LCS, utilizing local data and expanding the target population to include we not only high-risk individuals identified on the basis of smoking history but also those identified through other risk factors.
Methods
A decision tree combined with a state-transition Markov model was developed to simulate identification, diagnosis, and treatments for high-risk individuals, from a health care provider perspective. The selection criteria and screening effectiveness for high-risk individuals on the basis of smoking history were obtained from the Dutch-Belgian Lung Cancer Screening Study, targeting heavy smokers aged 50 to 74 years; whereas the Taiwan Lung Cancer Screening in Never-Smoker Trial was used to model high-risk individuals on the basis of factors other than smoking history. Local LC survival and cost data were used to populate the model. The willingness-to-pay threshold used in the study was US$24,302 to US$40,202 per quality-adjusted life-year (QALY).
Results
Screening led to additional early LC detected, and LC mortality reduction, compared with no screening. Over a lifetime horizon, the incremental cost-effectiveness ratio for high-risk individuals on the basis of smoking history was US$14,122 per QALY. The incremental cost-effectiveness ratio for high-risk individuals on the basis of factors other than smoking history was lower at US$9610 per QALY.
Conclusion
LCS with LDCT can be considered cost-effective in HK for high-risk individuals on the basis of smoking history and factors other than smoking history, contributing to the health benefits of the population. Our findings support a population-based LCS for all high-risk individuals identified through criteria beyond smoking history.
{"title":"Incorporating High-Risk Individuals Beyond Smoking History Into Lung Cancer Screening in Hong Kong: A Cost-Effectiveness Study","authors":"Herbert Ho-fung Loong MBBS, FRCP , Xuanqi Pan PhD , Carlos K.H. Wong PhD , Chao-Hua Chiu MD , Szu-Chun Yang MD , Matthew Shing Hin Chung BSc , Molly Siu Ching Li MBBS , Lisa de Jong PhD , Harry Groen MD, PhD , Maarten J. Postma PhD , Pan-Chyr Yang MD, PhD","doi":"10.1016/j.jtocrr.2025.100860","DOIUrl":"10.1016/j.jtocrr.2025.100860","url":null,"abstract":"<div><h3>Introduction</h3><div>Lung cancer (LC) accounts for 26.4% of all cancer deaths in Hong Kong (HK). Lung cancer screening (LCS) with low-dose computed tomography (LDCT) can reduce LC mortality. The cost-effectiveness of LDCT screening in high-risk individuals on the basis of smoking history has previously been investigated. However, nearly half of patients with LC in HK never smoke, indicating a different LC epidemiology compared with Western countries, where most LC cases are associated with smoking. We conducted a cost-effectiveness analysis for LCS, utilizing local data and expanding the target population to include we not only high-risk individuals identified on the basis of smoking history but also those identified through other risk factors.</div></div><div><h3>Methods</h3><div>A decision tree combined with a state-transition Markov model was developed to simulate identification, diagnosis, and treatments for high-risk individuals, from a health care provider perspective. The selection criteria and screening effectiveness for high-risk individuals on the basis of smoking history were obtained from the Dutch-Belgian Lung Cancer Screening Study, targeting heavy smokers aged 50 to 74 years; whereas the Taiwan Lung Cancer Screening in Never-Smoker Trial was used to model high-risk individuals on the basis of factors other than smoking history. Local LC survival and cost data were used to populate the model. The willingness-to-pay threshold used in the study was US$24,302 to US$40,202 per quality-adjusted life-year (QALY).</div></div><div><h3>Results</h3><div>Screening led to additional early LC detected, and LC mortality reduction, compared with no screening. Over a lifetime horizon, the incremental cost-effectiveness ratio for high-risk individuals on the basis of smoking history was US$14,122 per QALY. The incremental cost-effectiveness ratio for high-risk individuals on the basis of factors other than smoking history was lower at US$9610 per QALY.</div></div><div><h3>Conclusion</h3><div>LCS with LDCT can be considered cost-effective in HK for high-risk individuals on the basis of smoking history and factors other than smoking history, contributing to the health benefits of the population. Our findings support a population-based LCS for all high-risk individuals identified through criteria beyond smoking history.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100860"},"PeriodicalIF":3.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046211","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 : 2025-06-13DOI: 10.1016/j.jtocrr.2025.100859
Jay M. Lee MD , Jean-Louis Pujol MD, PhD , Jun Zhang MD, PhD , Oleg Leonov MD, PhD , Masahiro Tsuboi MD, PhD , Edward S. Kim MD, MBA , Calvin Ng MD , Nicolas Moreno-Mata MD, PhD , Amy Cummings MD, PhD , Ilhan Hacibekiroglu MD , Abidin Sehitogullari MD , Nirmal Veeramachaneni MD , Cathy Spillane PhD , Jiawei Duan PhD , Claudia Bossen PhD , Alexander Savchenko MD, PhD , Chiara Lobetti-Bodoni MD, PhD , Tony Mok MD , Pilar Garrido MD
Introduction
Canakinumab is a human monoclonal anti–interleukin-1β antibody with the potential to enhance the activity of programmed death-ligand 1 inhibitors by inhibiting protumor inflammation.
Methods
CANOPY-N was a randomized, phase 2 study to evaluate safety and efficacy of neoadjuvant canakinumab (200 mg subcutaneous once every three weeks) and pembrolizumab (200 mg intravenous once every three weeks), either in combination or alone, in patients with early-stage (stage Ib–IIIa) NSCLC. The primary end point was major pathologic response (MPR) rates (≤10% of residual tumor cells) by central pathology review in the arms containing canakinumab. Secondary end points included overall response rates, safety, pharmacokinetics, surgical feasibility rates, and MPR rate in the pembrolizumab arm. The impact of treatment on surgical outcomes was assessed as an exploratory outcome.
Results
In total, 88 patients were enrolled: 35 to the canakinumab arm, 35 to the canakinumab + pembrolizumab arm, and 18 to the pembrolizumab arm. One patient (2.9%) in the canakinumab arm (95% confidence interval [CI]: 0.07–14.92), six patients (17.1%) in the canakinumab + pembrolizumab arm (95% CI: 6.56–33.65), and three patients (16.7%) in the pembrolizumab arm (95% CI: 3.58–41.42) achieved MPR. No unexpected safety signals were observed. Of the 84 patients (95.5%) who underwent operation, the prespecified 6-week window was achieved for 72 patients (85.7%).
Conclusions
Neoadjuvant treatment with canakinumab alone or combined with pembrolizumab did not improve MPR rates compared with pembrolizumab alone. No unexpected safety signals were observed and canakinumab did not adversely affect surgical outcomes. Intraoperative perihilar or perilobular fibrosis after neoadjuvant immunotherapy was rare.
{"title":"CANOPY-N: A Phase 2 Study of Canakinumab or Pembrolizumab, Alone or in Combination, as Neoadjuvant Therapy in Patients With Resectable, Stage IB–IIIA NSCLC","authors":"Jay M. Lee MD , Jean-Louis Pujol MD, PhD , Jun Zhang MD, PhD , Oleg Leonov MD, PhD , Masahiro Tsuboi MD, PhD , Edward S. Kim MD, MBA , Calvin Ng MD , Nicolas Moreno-Mata MD, PhD , Amy Cummings MD, PhD , Ilhan Hacibekiroglu MD , Abidin Sehitogullari MD , Nirmal Veeramachaneni MD , Cathy Spillane PhD , Jiawei Duan PhD , Claudia Bossen PhD , Alexander Savchenko MD, PhD , Chiara Lobetti-Bodoni MD, PhD , Tony Mok MD , Pilar Garrido MD","doi":"10.1016/j.jtocrr.2025.100859","DOIUrl":"10.1016/j.jtocrr.2025.100859","url":null,"abstract":"<div><h3>Introduction</h3><div>Canakinumab is a human monoclonal anti–interleukin-1β antibody with the potential to enhance the activity of programmed death-ligand 1 inhibitors by inhibiting protumor inflammation.</div></div><div><h3>Methods</h3><div>CANOPY-N was a randomized, phase 2 study to evaluate safety and efficacy of neoadjuvant canakinumab (200 mg subcutaneous once every three weeks) and pembrolizumab (200 mg intravenous once every three weeks), either in combination or alone, in patients with early-stage (stage Ib–IIIa) NSCLC. The primary end point was major pathologic response (MPR) rates (≤10% of residual tumor cells) by central pathology review in the arms containing canakinumab. Secondary end points included overall response rates, safety, pharmacokinetics, surgical feasibility rates, and MPR rate in the pembrolizumab arm. The impact of treatment on surgical outcomes was assessed as an exploratory outcome.</div></div><div><h3>Results</h3><div>In total, 88 patients were enrolled: 35 to the canakinumab arm, 35 to the canakinumab + pembrolizumab arm, and 18 to the pembrolizumab arm. One patient (2.9%) in the canakinumab arm (95% confidence interval [CI]: 0.07–14.92), six patients (17.1%) in the canakinumab + pembrolizumab arm (95% CI: 6.56–33.65), and three patients (16.7%) in the pembrolizumab arm (95% CI: 3.58–41.42) achieved MPR. No unexpected safety signals were observed. Of the 84 patients (95.5%) who underwent operation, the prespecified 6-week window was achieved for 72 patients (85.7%).</div></div><div><h3>Conclusions</h3><div>Neoadjuvant treatment with canakinumab alone or combined with pembrolizumab did not improve MPR rates compared with pembrolizumab alone. No unexpected safety signals were observed and canakinumab did not adversely affect surgical outcomes. Intraoperative perihilar or perilobular fibrosis after neoadjuvant immunotherapy was rare.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 8","pages":"Article 100859"},"PeriodicalIF":3.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144579962","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 : 2025-06-13DOI: 10.1016/j.jtocrr.2025.100861
Yota Suzuki MD , Rajeev Dhupar MD , Inderpal S. Sarkaria MD, MBA , Ian G. Christie MD , Summer N. Mazur BS , Arjun Pennathur MD , James D. Luketich MD , Ryan M. Levy MD , Rodney J. Landreneau MD , Matthew J. Schuchert MD
Objective
Besides the discussion on parenchymal margin, data on the extent of lymph node (LN) dissection are scarce, especially in segmentectomy. This study aimed to investigate the extent of LN dissection and detection of occult disease in segmentectomy compared with lobar resection.
Methods
We performed a single-institution, retrospective analysis for patients who underwent segmentectomy or lobectomy for clinical T1N0M0 (≤3 cm) NSCLC from 2012 to 2022. The extent of LN dissection and the rate of detection of occult LN disease were compared. N1 nodes were further classified as collected as a specimen during the operation (N1 dissection) and the nodes retrieved from lung specimens by pathologists (N1 lung specimen).
Results
During the study period, 957 lobectomies and 402 segmentectomies were performed for clinical T1N0M0 NSCLC. The median number of sampled LNs was significantly higher in the lobectomy group (18 versus 12; p < 0.001). This tendency was similar across all node groups, including N2 nodes (7 versus 5), N1 dissection nodes (6 versus 4), and most significantly N1 lung specimen nodes (4 versus 0; all p < 0.001) There was a significant difference in N1 occult nodes (13.3% versus 3.7%; p < 0.001), whereas the difference was not significant in N2 occult nodes (5.5% versus 3.2%; p = 0.074).
Conclusions
Segmentectomy was associated with less LN sampling, which translated into lower detection of occult nodal metastasis in N1 LNs. Although standardized pathologic dissection could potentially improve detection, there is likely an inevitable inferiority in LN sampling with segmentectomy.
{"title":"Occult Node Detection With Lobectomy Versus Segmentectomy for Stage IA NSCLC","authors":"Yota Suzuki MD , Rajeev Dhupar MD , Inderpal S. Sarkaria MD, MBA , Ian G. Christie MD , Summer N. Mazur BS , Arjun Pennathur MD , James D. Luketich MD , Ryan M. Levy MD , Rodney J. Landreneau MD , Matthew J. Schuchert MD","doi":"10.1016/j.jtocrr.2025.100861","DOIUrl":"10.1016/j.jtocrr.2025.100861","url":null,"abstract":"<div><h3>Objective</h3><div>Besides the discussion on parenchymal margin, data on the extent of lymph node (LN) dissection are scarce, especially in segmentectomy. This study aimed to investigate the extent of LN dissection and detection of occult disease in segmentectomy compared with lobar resection.</div></div><div><h3>Methods</h3><div>We performed a single-institution, retrospective analysis for patients who underwent segmentectomy or lobectomy for clinical T1N0M0 (≤3 cm) NSCLC from 2012 to 2022. The extent of LN dissection and the rate of detection of occult LN disease were compared. N1 nodes were further classified as collected as a specimen during the operation (N1 dissection) and the nodes retrieved from lung specimens by pathologists (N1 lung specimen).</div></div><div><h3>Results</h3><div>During the study period, 957 lobectomies and 402 segmentectomies were performed for clinical T1N0M0 NSCLC. The median number of sampled LNs was significantly higher in the lobectomy group (18 versus 12; <em>p</em> < 0.001). This tendency was similar across all node groups, including N2 nodes (7 versus 5), N1 dissection nodes (6 versus 4), and most significantly N1 lung specimen nodes (4 versus 0; all <em>p</em> < 0.001) There was a significant difference in N1 occult nodes (13.3% versus 3.7%; <em>p</em> < 0.001), whereas the difference was not significant in N2 occult nodes (5.5% versus 3.2%; <em>p</em> = 0.074).</div></div><div><h3>Conclusions</h3><div>Segmentectomy was associated with less LN sampling, which translated into lower detection of occult nodal metastasis in N1 LNs. Although standardized pathologic dissection could potentially improve detection, there is likely an inevitable inferiority in LN sampling with segmentectomy.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 8","pages":"Article 100861"},"PeriodicalIF":3.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588218","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 : 2025-06-13eCollection Date: 2025-09-01DOI: 10.1016/j.jtocrr.2025.100863
Heather Law, Huamao M Lin, Eileen Curran, Annette Szumski, Jacinta Wiens, Jennifer Blender, Emily S Venanzi, Erin L Schenk, Jessica J Lin, Jennifer C King
Introduction: This study investigated quality of life (QoL) and its role in treatment decision making among patients with anaplastic lymphoma kinase (ALK)+ NSCLC.
Methods: Adult patients with self-reported ALK+ NSCLC residing in the United States from the Lung Cancer Registry from GO2 for Lung Cancer were included. Measures included a core patient survey derived from Quality of Life Questionnaire - Core 30 items (QLQ-C30) and QLQ - lung cancer module 29 items domains and an ALK+ NSCLC module (ALK module). Associations were assessed between key domains and module questions using polyserial or Spearman's correlations and Cochran-Mantel-Haenszel tests.
Results: Seventy-one patients with ALK+ NSCLC completed the ALK module. Most patients (85%) felt their current therapy helped stop cancer growth, helped them live longer, and was worth taking despite side effects; however, 80% reported some cancer scan-related anxiety and only 32% reported having received "quite a bit" or "very much" mental health support information from their care team. Most patients (75%) reported QoL as a top concern in treatment decisions, regardless of responses to other ALK module questions (all associations p ≥ 0.50). Although most patients (87%) perceived their physicians as interested in their QoL, only 51% reported their physicians discussed QoL as a top concern in treatment decisions. QLQ-C30 composite global health status-QoL score had significant moderate to strong correlations with all other QLQ-C30 and lung cancer module 29 items domains (p ≤ 0.004) and some components of communication with care teams, treatment confidence, and impact on daily life.
Conclusions: QoL is important in treatment decision making for patients with ALK+ NSCLC. These findings highlight areas for improvement in mental health support and patient-provider communication.
{"title":"Role of Quality of Life in Daily Functioning, Communication with Care Teams, and Treatment Decisions in Patients with <i>ALK</i>+ NSCLC.","authors":"Heather Law, Huamao M Lin, Eileen Curran, Annette Szumski, Jacinta Wiens, Jennifer Blender, Emily S Venanzi, Erin L Schenk, Jessica J Lin, Jennifer C King","doi":"10.1016/j.jtocrr.2025.100863","DOIUrl":"10.1016/j.jtocrr.2025.100863","url":null,"abstract":"<p><strong>Introduction: </strong>This study investigated quality of life (QoL) and its role in treatment decision making among patients with anaplastic lymphoma kinase (<i>ALK</i>)+ NSCLC.</p><p><strong>Methods: </strong>Adult patients with self-reported <i>ALK</i>+ NSCLC residing in the United States from the Lung Cancer Registry from GO2 for Lung Cancer were included. Measures included a core patient survey derived from Quality of Life Questionnaire - Core 30 items (QLQ-C30) and QLQ - lung cancer module 29 items domains and an <i>ALK+</i> NSCLC module (ALK module). Associations were assessed between key domains and module questions using polyserial or Spearman's correlations and Cochran-Mantel-Haenszel tests.</p><p><strong>Results: </strong>Seventy-one patients with <i>ALK</i>+ NSCLC completed the ALK module. Most patients (85%) felt their current therapy helped stop cancer growth, helped them live longer, and was worth taking despite side effects; however, 80% reported some cancer scan-related anxiety and only 32% reported having received \"quite a bit\" or \"very much\" mental health support information from their care team. Most patients (75%) reported QoL as a top concern in treatment decisions, regardless of responses to other ALK module questions (all associations <i>p</i> ≥ 0.50). Although most patients (87%) perceived their physicians as interested in their QoL, only 51% reported their physicians discussed QoL as a top concern in treatment decisions. QLQ-C30 composite global health status-QoL score had significant moderate to strong correlations with all other QLQ-C30 and lung cancer module 29 items domains (<i>p</i> ≤ 0.004) and some components of communication with care teams, treatment confidence, and impact on daily life.</p><p><strong>Conclusions: </strong>QoL is important in treatment decision making for patients with <i>ALK+</i> NSCLC. These findings highlight areas for improvement in mental health support and patient-provider communication.</p>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 9","pages":"100863"},"PeriodicalIF":3.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873869","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}
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