IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-02-27 DOI: 10.1016/j.lungcan.2025.108463

Stephanie P.L. Saw , Angela Takano , Siqin Zhou , Nwe Oo Hlaing , Anne James , Craig Joseph , Gillianne G.Y. Lai , Darren W.T. Lim , Ravindran Kanesvaran , Mei-Kim Ang , Quan Sing Ng , Amit Jain , Wan Ling Tan , Yi Lin Teh , Aaron C. Tan , Boon-Hean Ong , Tony K.H. Lim , Joe P.S. Yeong , Sze Huey Tan , Daniel S.W. Tan

Background

The predictive value of PD-L1 to select patients for immunotherapy in resectable NSCLC remains imprecise, confounded by different assays used across trials and intra-tumoural heterogeneity (ITH). We sought to compare the concordance between 3 PD-L1 antibodies stratified by EGFR mutation status, evaluate ITH and implications on survival outcomes.

Methods

Tissue microarrays were constructed from stage IA-IIIA NSCLC with 3 tumour cores per patient. Tumour proportion score (TPS) was evaluated by 3 pathologists for SP263, SP142, 22C3 and analysed in tertiles of < 1 %, 1–49 % and ≥ 50 %. ITH was defined as discordant TPS in ≥ 2/3 tumour cores. Cohen’s kappa test was used to assess agreement. Survival outcomes were estimated using Kaplan-Meier.

Results

A total of 561 patients were included, 59.5% (334/561) were EGFR-mutant. Stage IA comprised 45.5%(255/561), IB 24.1%(135/561), IIA 12.7%(71/561), IIB 4.5%(25/561) and IIIA 13.4%(75/561).

Across 1683 tumour cores, SP263 and 22C3 had the highest concordance (Kappa = 0.689), followed by 22C3 and SP142 (Kappa = 0.354), then SP263 and SP142 (Kappa = 0.284), similar between EGFR-mutant and EGFR-wildtype. Agreement between pathologists was almost perfect.

ITH by SP263 was observed in 14.1 % of EGFR-mutant versus 24.2 % in EGFR-wildtype(p = 0.002). Discordance was highest among TPS 1–49 % at 92.6 % (88/95) followed by ≥ 50 % at 37.8 % (14/37) and least among < 1 % at 0 % (0/429) (p < 0.001). For tumour cores scored 1–49 %, 63 %/70 % of adjacent cores were scored < 1 % for EGFR-wildtype/mutant respectively. Histological grade was the only independent predictor of PD-L1 ITH on multivariable analysis. PD-L1 ITH was not associated with survival on multivariable analysis.

Conclusion

PD-L1 scoring by SP263 and 22C3 are interchangeable but not SP142 regardless of EGFR status. PD-L1 ITH was more common in EGFR-wildtype versus EGFR-mutant tumours. Extra care should be taken to select the most representative tumour core for tumours with high histological grade or TPS 1–49% as this may influence peri-operative treatment decisions.

{"title":"EGFR mutation status affects intra-tumoural heterogeneity of PD-L1 expression but not agreement between assays in resectable non-small cell lung cancer","authors":"Stephanie P.L. Saw , Angela Takano , Siqin Zhou , Nwe Oo Hlaing , Anne James , Craig Joseph , Gillianne G.Y. Lai , Darren W.T. Lim , Ravindran Kanesvaran , Mei-Kim Ang , Quan Sing Ng , Amit Jain , Wan Ling Tan , Yi Lin Teh , Aaron C. Tan , Boon-Hean Ong , Tony K.H. Lim , Joe P.S. Yeong , Sze Huey Tan , Daniel S.W. Tan","doi":"10.1016/j.lungcan.2025.108463","DOIUrl":"10.1016/j.lungcan.2025.108463","url":null,"abstract":"<div><h3>Background</h3><div>The predictive value of PD-L1 to select patients for immunotherapy in resectable NSCLC remains imprecise, confounded by different assays used across trials and intra-tumoural heterogeneity (ITH). We sought to compare the concordance between 3 PD-L1 antibodies stratified by EGFR mutation status, evaluate ITH and implications on survival outcomes.</div></div><div><h3>Methods</h3><div>Tissue microarrays were constructed from stage IA-IIIA NSCLC with 3 tumour cores per patient. Tumour proportion score (TPS) was evaluated by 3 pathologists for SP263, SP142, 22C3 and analysed in tertiles of < 1 %, 1–49 % and ≥ 50 %. ITH was defined as discordant TPS in ≥ 2/3 tumour cores. Cohen’s kappa test was used to assess agreement. Survival outcomes were estimated using Kaplan-Meier.</div></div><div><h3>Results</h3><div>A total of 561 patients were included, 59.5% (334/561) were EGFR-mutant. Stage IA comprised 45.5%(255/561), IB 24.1%(135/561), IIA 12.7%(71/561), IIB 4.5%(25/561) and IIIA 13.4%(75/561).</div><div>Across 1683 tumour cores, SP263 and 22C3 had the highest concordance (Kappa = 0.689), followed by 22C3 and SP142 (Kappa = 0.354), then SP263 and SP142 (Kappa = 0.284), similar between EGFR-mutant and EGFR-wildtype. Agreement between pathologists was almost perfect.</div><div>ITH by SP263 was observed in 14.1 % of EGFR-mutant versus 24.2 % in EGFR-wildtype(p = 0.002). Discordance was highest among TPS 1–49 % at 92.6 % (88/95) followed by ≥ 50 % at 37.8 % (14/37) and least among < 1 % at 0 % (0/429) (p < 0.001). For tumour cores scored 1–49 %, 63 %/70 % of adjacent cores were scored < 1 % for EGFR-wildtype/mutant respectively. Histological grade was the only independent predictor of PD-L1 ITH on multivariable analysis. PD-L1 ITH was not associated with survival on multivariable analysis.</div></div><div><h3>Conclusion</h3><div>PD-L1 scoring by SP263 and 22C3 are interchangeable but not SP142 regardless of EGFR status. PD-L1 ITH was more common in EGFR-wildtype versus EGFR-mutant tumours. Extra care should be taken to select the most representative tumour core for tumours with high histological grade or TPS 1–49% as this may influence <em>peri</em>-operative treatment decisions.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"202 ","pages":"Article 108463"},"PeriodicalIF":4.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to "Real-world treatment sequencing and effectiveness of second- and third-generation ALK tyrosine kinase inhibitors for ALK-positive advanced non-small cell lung cancer" [Lung Cancer 195 (2024) 107919].

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-02-22 DOI: 10.1016/j.lungcan.2025.108441

Jessica R Bauman, Geoffrey Liu, Isabel Preeshagul, Stephen V Liu, Barbara Melosky, Devin Abrahami, Benjamin Li, Despina Thomaidou, Kirsten Duncan, Stan Krulewicz, Martin Rupp, Jessica J Lin

引用次数: 0

Long-term outcomes of neoadjuvant gefitinib in resectable stage II-IIIA non-small cell lung cancer: A phase II, prospective cohort study

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-02-22 DOI: 10.1016/j.lungcan.2025.108457

Zhanming Ma , Fangqiu Fu , Yang Zhang , Haiquan Chen

Background

Our previous study has showed the safety and efficacy of preoperative gefitinib in patients with stage II-IIIA resectable non–small cell lung cancer (NSCLC). This study aimed to report the long-term survival analysis and recurrent patterns.

Methods

This was a single-arm, phase II clinical trial. Patients with resectable stage II-IIIA NSCLC harboring EGFR exon 19 deletion or exon 21 L858R mutations were enrolled. Patients were administrated with preoperative gefitinib (250 mg once daily for 42 days), followed by surgical resection. The primary endpoint was objective response rate (ORR); secondary endpoints included the rate of major pathologic response (MPR), disease-free survival (DFS), overall survival (OS). MPR was defined as the presence of no more than 10 % viable tumor. Chi-square test was used to assess the differences in CNS recurrence rates and recurrent patterns.

Results

Of the 33 intention-to-treat patients, ORR was 54.5 % (95 % confidence interval (CI), 37.7–70.7), and the rate of MPR was 24.2 % (95 % CI, 11.9–40.4). Among the investigated 28 patients, the median follow-up was 108.5 months. The median OS was 89.8 months (95 % CI, 44.37–NC), and the median DFS was 36.4 months (95 % CI, 18.9–NC). In addition, MPR continued to indicate significantly improved DFS, as well as OS (DFS, p = 0.015; OS, p = 0.037). The neoadjuvant gefitinib group showed prolonged DFS and OS than platinum doublet group (hazard ratio (HR) = 1.71, 95 % CI, 1.02–2.85, p = 0.038; and HR = 2.31; 95 % CI, 1.28–4.16, p = 0.0044, respectively). There was a significant difference in the distant recurrence patterns between the two groups (p = 0.032). Moreover, the gefitinib group showed similar overall brain metastasis rate than platinum doublet group (21.4 % versus 27.5 %).

Conclusions

With satisfying prognosis benefits and acceptable brain metastasis rate in long-term follow-up, gefitinib exhibited clinical viability for operable stage II-IIIA EGFR-mutant NSCLC over chemotherapy in the neoadjuvant setting. MPR was significantly associated with both prolonged DFS and OS, manifesting its potential as an essential endpoint for future neoadjuvant trials.

{"title":"Long-term outcomes of neoadjuvant gefitinib in resectable stage II-IIIA non-small cell lung cancer: A phase II, prospective cohort study","authors":"Zhanming Ma , Fangqiu Fu , Yang Zhang , Haiquan Chen","doi":"10.1016/j.lungcan.2025.108457","DOIUrl":"10.1016/j.lungcan.2025.108457","url":null,"abstract":"<div><h3>Background</h3><div>Our previous study has showed the safety and efficacy of preoperative gefitinib in patients with stage II-IIIA resectable non–small cell lung cancer (NSCLC). This study aimed to report the long-term survival analysis and recurrent patterns.</div></div><div><h3>Methods</h3><div>This was a single-arm, phase II clinical trial. Patients with resectable stage II-IIIA NSCLC harboring EGFR exon 19 deletion or exon 21 L858R mutations were enrolled. Patients were administrated with preoperative gefitinib (250 mg once daily for 42 days), followed by surgical resection. The primary endpoint was objective response rate (ORR); secondary endpoints included the rate of major pathologic response (MPR), disease-free survival (DFS), overall survival (OS). MPR was defined as the presence of no more than 10 % viable tumor. Chi-square test was used to assess the differences in CNS recurrence rates and recurrent patterns.</div></div><div><h3>Results</h3><div>Of the 33 intention-to-treat patients, ORR was 54.5 % (95 % confidence interval (CI), 37.7–70.7), and the rate of MPR was 24.2 % (95 % CI, 11.9–40.4). Among the investigated 28 patients, the median follow-up was 108.5 months. The median OS was 89.8 months (95 % CI, 44.37–NC), and the median DFS was 36.4 months (95 % CI, 18.9–NC). In addition, MPR continued to indicate significantly improved DFS, as well as OS (DFS, <em>p</em> = 0.015; OS, <em>p</em> = 0.037). The neoadjuvant gefitinib group showed prolonged DFS and OS than platinum doublet group (hazard ratio (HR) = 1.71, 95 % CI, 1.02–2.85, <em>p</em> = 0.038; and HR = 2.31; 95 % CI, 1.28–4.16, <em>p</em> = 0.0044, respectively). There was a significant difference in the distant recurrence patterns between the two groups (<em>p</em> = 0.032). Moreover, the gefitinib group showed similar overall brain metastasis rate than platinum doublet group (21.4 % versus 27.5 %).</div></div><div><h3>Conclusions</h3><div>With satisfying prognosis benefits and acceptable brain metastasis rate in long-term follow-up, gefitinib exhibited clinical viability for operable stage II-IIIA <em>EGFR</em>-mutant NSCLC over chemotherapy in the neoadjuvant setting. MPR was significantly associated with both prolonged DFS and OS, manifesting its potential as an essential endpoint for future neoadjuvant trials.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"201 ","pages":"Article 108457"},"PeriodicalIF":4.5,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to "Real-world comparative effectiveness of sotorasib versus docetaxel in second line and beyond among patients with advanced non-small cell lung cancer (NSCLC)" [Lung Cancer 197 (2024) 107960].

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-02-20 DOI: 10.1016/j.lungcan.2025.108440

Melissa Johnson, Diana Younan, Shia T Kent, Marco Mesa Frias, M Alan Brookhart, Akhila Balasubramanian, Alexander Spira

引用次数: 0

A randomised non-comparative phase II study of atezolizumab, bevacizumab and chemotherapy in EGFR-mutant NSCLC with acquired resistance – The ETOP 15-19 ABC-lung trial

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-02-20 DOI: 10.1016/j.lungcan.2025.108454

R.A. Soo , K. Vervita , M. Früh , B.C. Cho , M. Majem , D. Rodriguez Abreu , K. Ribi , A. Callejo , T. Moran , M. Domine Gomez , M. Provencio , A. Addeo , J.Y. Han , A.L. Ortega Granados , M. Reck , A. Blasco , R. Garcia Campelo , M.A. Sala González , C. Britschgi , H. Roschitzki-Voser , R.A. Stahel

Background

ABC-lung explores the potential effect of combining atezolizumab and bevacizumab with either carboplatin/paclitaxel (ABCPac) or pemetrexed (ABPem) in patients with EGFR-mutant NSCLC, resistant to tyrosine kinase inhibitors (TKIs).

Methods

ABC-lung is a 1:1 randomised, non-comparative, phase II trial, stratified by prior treatment with a third-generation EGFR TKI, evaluating atezolizumab (1200 mg, Q3W) and bevacizumab (15mg/kg, Q3W) with either 4-6 cycles of carboplatin (AUC5, Q3W) and paclitaxel (175-200 mg/m2, Q3W) or pemetrexed (500 mg/m2, Q3W) until progression (PD). The study aimed to improve the 1-year progression-free survival (PFS) rate from 18% to 37%, assessed per RECISTv1.1, separately in each arm. To reject the null hypothesis, at least 14 of 45 evaluable patients in each arm needed to be progression-free at 1-year (power 83%, 1-sided a=0.023). Secondary endpoints included overall survival (OS), objective response rate (ORR), PFS, quality of life (QoL) and adverse events (AEs).

Results

Between 09/2020 and 09/2022, 95 patients were randomized (ABCPac:45; ABPem:50) with median follow-up time of 19 months. From the evaluable patients, 9 in ABCPac and 11 in ABPem arms reached 1-year without progression, lower than the success criterion of 14 patients. Median PFS was 6.4 months in ABCPac and 7.6 months in the ABPem arms, while median OS was 15.4 months and 15.6 months, respectively. Grade ≥3 treatment-related AEs were experienced by 50% and 42% of patients in ABCPac and ABPem arms, respectively, while no grade 5 AEs were recorded.

Conclusions

The observed 1-year PFS rate with atezolizumab, bevacizumab in combination with either carboplatin-paclitaxel or pemetrexed was below the aspired rate of 37% in both arms. The safety is consistent with the known toxicity profiles.

Clinical trial identification: NCT04245085.

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引用次数: 0

Delayed central nervous system progression with atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer (LU23-15) 阿特珠单抗联合化疗治疗广泛期小细胞肺癌可延缓中枢神经系统进展 (LU23-15)

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-02-19 DOI: 10.1016/j.lungcan.2025.108455

Kyoungmin Lee , Tae-Hwan Kim , Sung Yong Lee , Yun-Gyoo Lee , Juwhan Choi , Jin-Hyuk Choi , Jung Yoon Choi , Ah-reum Lim , Jung Sun Kim , Ji Won Lee , Yoon Ji Choi , Ji Hyun Park , Yoon Namgung , Hee Kyung Ahn , Eun Joo Kang

Background

The combination of atezolizumab with etoposide and carboplatin (AECb) has become a new standard of care for extensive-stage small-cell lung cancer (ES-SCLC). This study evaluates its impact on central nervous system (CNS) progression, specifically brain metastases.

Method

We analyzed the outcomes of 550 ES-SCLC patients who received first-line therapy between 2016 and 2022, focusing on time to intracranial progression (TTicP), progression-free survival (PFS), and overall survival (OS).

Results

Of the 550 patients, 247 (44.9 %) received AECb, while 303 (55.1 %) received conventional chemotherapy (CTx). Intracranial progression occurred in 179 patients (32.5 %), with the AECb group showing a significantly prolonged TTicP compared to the CTx group (median 24.4 vs. 14.3 months; p = 0.038). In patients without brain metastasis at diagnosis (n = 408), TTicP was also longer in the AECb group (27.2 vs. 15.3 months; p = 0.016). This benefit persisted even after excluding patients who underwent prophylactic cranial irradiation (PCI) (27.2 vs. 15.2 months; p = 0.02) (n = 394). These findings remained consistent after adjusting for age, initial metastatic site, and PCI. Additionally, the AECb group showed improved PFS (5.0 vs. 4.7 months; p = 0.004) and OS (11.1 vs. 9.8 months; p = 0.003).

Conclusion

Our findings suggest that the AECb regimen is superior to conventional chemotherapy in delaying CNS progression and controlling systemic disease in ES-SCLC. These results support the AECb regimen as the new standard of care. Further research is needed to explore the mechanisms behind these improved CNS outcomes and to reassess the necessity of PCI in this treatment era.

{"title":"Delayed central nervous system progression with atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer (LU23-15)","authors":"Kyoungmin Lee , Tae-Hwan Kim , Sung Yong Lee , Yun-Gyoo Lee , Juwhan Choi , Jin-Hyuk Choi , Jung Yoon Choi , Ah-reum Lim , Jung Sun Kim , Ji Won Lee , Yoon Ji Choi , Ji Hyun Park , Yoon Namgung , Hee Kyung Ahn , Eun Joo Kang","doi":"10.1016/j.lungcan.2025.108455","DOIUrl":"10.1016/j.lungcan.2025.108455","url":null,"abstract":"<div><h3>Background</h3><div>The combination of atezolizumab with etoposide and carboplatin (AECb) has become a new standard of care for extensive-stage small-cell lung cancer (ES-SCLC). This study evaluates its impact on central nervous system (CNS) progression, specifically brain metastases.</div></div><div><h3>Method</h3><div>We analyzed the outcomes of 550 ES-SCLC patients who received first-line therapy between 2016 and 2022, focusing on time to intracranial progression (TTicP), progression-free survival (PFS), and overall survival (OS).</div></div><div><h3>Results</h3><div>Of the 550 patients, 247 (44.9 %) received AECb, while 303 (55.1 %) received conventional chemotherapy (CTx). Intracranial progression occurred in 179 patients (32.5 %), with the AECb group showing a significantly prolonged TTicP compared to the CTx group (median 24.4 vs. 14.3 months; p = 0.038). In patients without brain metastasis at diagnosis (n = 408), TTicP was also longer in the AECb group (27.2 vs. 15.3 months; p = 0.016). This benefit persisted even after excluding patients who underwent prophylactic cranial irradiation (PCI) (27.2 vs. 15.2 months; p = 0.02) (n = 394). These findings remained consistent after adjusting for age, initial metastatic site, and PCI. Additionally, the AECb group showed improved PFS (5.0 vs. 4.7 months; p = 0.004) and OS (11.1 vs. 9.8 months; p = 0.003).</div></div><div><h3>Conclusion</h3><div>Our findings suggest that the AECb regimen is superior to conventional chemotherapy in delaying CNS progression and controlling systemic disease in ES-SCLC. These results support the AECb regimen as the new standard of care. Further research is needed to explore the mechanisms behind these improved CNS outcomes and to reassess the necessity of PCI in this treatment era.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"201 ","pages":"Article 108455"},"PeriodicalIF":4.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NUT carcinoma in children and adolescents: An analysis of the European Cooperative Study Group on pediatric rare tumors (EXPeRT)

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-02-19 DOI: 10.1016/j.lungcan.2025.108449

Tim Flaadt , Lauriane Lemelle , Michael Abele , Calogero Virgone , Tal Ben-Ami , Denis Kachanov , Apostolos Pourtsidis , Andrea Ferrari , Gianni Bisogno , Ewa Bien , Nuno Jorge Dos Reis Farinha , Jan Godzinski , Yves Reguerre , Jelena Roganovic , Linus D. Kloker , Ulrich M. Lauer , Dominik T. Schneider , Ines B. Brecht , Daniel Orbach

Background and Aims

NUT carcinoma (NC) is a sporadic, highly aggressive tumor that primarily affects children, adolescents, and young adults and is characterized by the presence of somatic NUTM1 rearrangements. This analysis by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) aims to fill the knowledge gap regarding the clinical characteristics of children with NC.

Methods

A retrospective case series of NC-patients aged 0–18 years treated between 2011 and 2023 was conducted using the EXPeRT database. Relevant clinical characteristics, including treatment and outcome were recorded.

Results

Twenty-seven patients with a median age of 13 years (range 7–18) were analyzed. Thirteen patients were initially misdiagnosed. Sixteen patients had thoracic and 11 extra-thoracic tumors, including three in the nasal/sinus region and two in the submandibular glands. Despite intense multimodal treatment, median event-free and overall survivals were 1.5 and 6.5 months, respectively.

Conclusions

Early diagnosis of NC by examination of the NUTM1 rearrangement in undifferentiated or poorly differentiated carcinomas is crucial in order to initiate specific and intensive therapy as quickly as possible. Similar to adult patients, only a minority of pediatric patients achieved prolonged survival. Therefore, the development of novel therapeutic strategies in future joint clinical trials is essential.

{"title":"NUT carcinoma in children and adolescents: An analysis of the European Cooperative Study Group on pediatric rare tumors (EXPeRT)","authors":"Tim Flaadt , Lauriane Lemelle , Michael Abele , Calogero Virgone , Tal Ben-Ami , Denis Kachanov , Apostolos Pourtsidis , Andrea Ferrari , Gianni Bisogno , Ewa Bien , Nuno Jorge Dos Reis Farinha , Jan Godzinski , Yves Reguerre , Jelena Roganovic , Linus D. Kloker , Ulrich M. Lauer , Dominik T. Schneider , Ines B. Brecht , Daniel Orbach","doi":"10.1016/j.lungcan.2025.108449","DOIUrl":"10.1016/j.lungcan.2025.108449","url":null,"abstract":"<div><h3>Background and Aims</h3><div>NUT carcinoma (NC) is a sporadic, highly aggressive tumor that primarily affects children, adolescents, and young adults and is characterized by the presence of somatic <em>NUTM1</em> rearrangements. This analysis by the European Cooperative Study Group for Pediatric Rare Tumors (<em>EXPeRT</em>) aims to fill the knowledge gap regarding the clinical characteristics of children with NC.</div></div><div><h3>Methods</h3><div>A retrospective case series of NC-patients aged 0–18 years treated between 2011 and 2023 was conducted using the <em>EXPeRT</em> database. Relevant clinical characteristics, including treatment and outcome were recorded.</div></div><div><h3>Results</h3><div>Twenty-seven patients with a median age of 13 years (range 7–18) were analyzed. Thirteen patients were initially misdiagnosed. Sixteen patients had thoracic and 11 extra-thoracic tumors, including three in the nasal/sinus region and two in the submandibular glands. Despite intense multimodal treatment, median event-free and overall survivals were 1.5 and 6.5 months, respectively.</div></div><div><h3>Conclusions</h3><div>Early diagnosis of NC by examination of the NUTM1 rearrangement in undifferentiated or poorly differentiated carcinomas is crucial in order to initiate specific and intensive therapy as quickly as possible. Similar to adult patients, only a minority of pediatric patients achieved prolonged survival. Therefore, the development of novel therapeutic strategies in future joint clinical trials is essential.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"201 ","pages":"Article 108449"},"PeriodicalIF":4.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparative effectiveness and safety of tislelizumab versus other anti–PD-(L)1 agents in first- and subsequent lines in locally advanced or metastatic non–small cell lung cancer: Systematic literature review and network meta-analysis tislelizumab 与其他抗 PD-(L)1 药物在局部晚期或转移性非小细胞肺癌一线和后续治疗中的有效性和安全性比较：系统文献综述和网络荟萃分析

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-02-17 DOI: 10.1016/j.lungcan.2025.108450

Nicolas Girard , Ji-Youn Han , Ross A. Soo , Kaijun Wang , Wenxi Tang , Georgios F. Nikolaidis , Anastasios Tasoulas , Ifigeneia Barouma , JeanPierre Coaquira Castro , Zheyuan Yang , Tanushree Chaudhary , Lin Zhan

Objectives

To estimate the relative efficacy and safety of tislelizumab with or without chemotherapy in patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) in first-line (1L) squamous, 1L non-squamous with programmed death-ligand 1 (PD-L1) ≥ 50 %, and second- and subsequent lines (2L + ) settings via indirect treatment comparisons, following a systematic literature review (SLR) of studies investigating existing anti–programmed cell death protein-(ligand)1 (PD-[L]1) therapies.

Methods

The SLR was originally conducted in 2022 and updated in 2023. A feasibility assessment (FA) was undertaken to assess the assumptions required for network meta-analysis (NMA) among therapies approved in the UK and European Union aligning with tislelizumab’s license. Outcomes included overall survival (OS), progression-free survival (PFS), and grade ≥ 3 treatment-related adverse events (TRAEs). Analyses were conducted in the hazard ratio scale for OS and PFS and in the odds ratio scale for TRAEs. Uncertainty was expressed in 95 % credible intervals.

Results

The SLR identified 277 total studies in 1L and 176 in 2L + NSCLC, with 23 and eight carried forward to their respective FAs. After the FA stage, 20 and eight studies qualified for the 1L and 2L + NMAs, respectively. Tislelizumab with or without chemotherapy was statistically significantly more favorable than most comparator treatments and ranked as best or second-best treatment overall for the following: PFS in 1L squamous NSCLC, OS/PFS in 1L non-squamous NSCLC with PD-L1 ≥ 50 %, and OS/PFS/TRAEs in 2L + NSCLC of any histology. For the remaining analyses (i.e. OS/TRAEs in 1L squamous NSCLC), tislelizumab with or without chemotherapy was comparable to other anti–PD-(L)1 therapies and combination therapies.

Conclusions

Tislelizumab with or without chemotherapy appears to be comparable to or more favorable than other regimens of anti–PD-(L)1 therapies or combination therapies in OS/PFS/TRAEs across patients with 1L squamous NSCLC, 1L non-squamous NSCLC with PD-L1 ≥ 50 %, and 2L + NSCLC of any histology.

{"title":"Comparative effectiveness and safety of tislelizumab versus other anti–PD-(L)1 agents in first- and subsequent lines in locally advanced or metastatic non–small cell lung cancer: Systematic literature review and network meta-analysis","authors":"Nicolas Girard , Ji-Youn Han , Ross A. Soo , Kaijun Wang , Wenxi Tang , Georgios F. Nikolaidis , Anastasios Tasoulas , Ifigeneia Barouma , JeanPierre Coaquira Castro , Zheyuan Yang , Tanushree Chaudhary , Lin Zhan","doi":"10.1016/j.lungcan.2025.108450","DOIUrl":"10.1016/j.lungcan.2025.108450","url":null,"abstract":"<div><h3>Objectives</h3><div>To estimate the relative efficacy and safety of tislelizumab with or without chemotherapy in patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) in first-line (1L) squamous, 1L non-squamous with programmed death-ligand 1 (PD-L1) ≥ 50 %, and second- and subsequent lines (2L + ) settings via indirect treatment comparisons, following a systematic literature review (SLR) of studies investigating existing anti–programmed cell death protein-(ligand)1 (PD-[L]1) therapies.</div></div><div><h3>Methods</h3><div>The SLR was originally conducted in 2022 and updated in 2023. A feasibility assessment (FA) was undertaken to assess the assumptions required for network <em>meta</em>-analysis (NMA) among therapies approved in the UK and European Union aligning with tislelizumab’s license. Outcomes included overall survival (OS), progression-free survival (PFS), and grade ≥ 3 treatment-related adverse events (TRAEs). Analyses were conducted in the hazard ratio scale for OS and PFS and in the odds ratio scale for TRAEs. Uncertainty was expressed in 95 % credible intervals.</div></div><div><h3>Results</h3><div>The SLR identified 277 total studies in 1L and 176 in 2L + NSCLC, with 23 and eight carried forward to their respective FAs. After the FA stage, 20 and eight studies qualified for the 1L and 2L + NMAs, respectively. Tislelizumab with or without chemotherapy was statistically significantly more favorable than most comparator treatments and ranked as best or second-best treatment overall for the following: PFS in 1L squamous NSCLC, OS/PFS in 1L non-squamous NSCLC with PD-L1 ≥ 50 %, and OS/PFS/TRAEs in 2L + NSCLC of any histology. For the remaining analyses (i.e. OS/TRAEs in 1L squamous NSCLC), tislelizumab with or without chemotherapy was comparable to other anti–PD-(L)1 therapies and combination therapies.</div></div><div><h3>Conclusions</h3><div>Tislelizumab with or without chemotherapy appears to be comparable to or more favorable than other regimens of anti–PD-(L)1 therapies or combination therapies in OS/PFS/TRAEs across patients with 1L squamous NSCLC, 1L non-squamous NSCLC with PD-L1 ≥ 50 %, and 2L + NSCLC of any histology.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"201 ","pages":"Article 108450"},"PeriodicalIF":4.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evolving treatments and prognosis in Stage IV non-small cell lung cancer: 20 years of progress of novel therapies

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-02-17 DOI: 10.1016/j.lungcan.2025.108453

Hironori Satoh , Yusuke Okuma , Yuki Shinno , Ken Masuda , Yuji Matsumoto , Tatsuya Yoshida , Yasushi Goto , Hidehito Horinouchi , Noboru Yamamoto , Yuichiro Ohe

Background

Advancements in pharmacotherapy, including molecular targeted therapies and immune checkpoint inhibitors, have revolutionized the treatment for Stage IV non-small cell lung cancer (NSCLC) over the past two decades. However, differences in drug approval timelines across countries raise important questions about their impact on survival rates. This study investigates trends in overall survival (OS), patient characteristics, and the association between OS improvements and the introduction of new drugs.

Patients and methods

This retrospective review included patients with Stage IV NSCLC treated at the National Cancer Center Hospital in Japan from 2001 to 2021. Using data from the Department of Thoracic Oncology registries, 2,555 patients were identified and categorized into four time periods: 2001–2005 (Group A), 2006–2010 (Group B), 2011–2015 (Group C), and 2016–2021 (Group D).

Results

While baseline characteristics remained relatively consistent, Group D had an increased proportion of elderly patients (≥ 75 years) and those with brain metastases. Additionally, the gender ratio became more balanced over time. Notably, Group D patients with EGFR mutations or ALK fusion positivity and older age demonstrated significantly longer OS. Analysis revealed steady and substantial improvements in OS across time periods (median OS: Group A, 10.68 months; Group B, 14.12 months; Group C, 16.49 months; and Group D, 25.46 months, respectively).

Conclusions

This study demonstrates marked improvements in survival for patients with Stage IV NSCLC, particularly in the last six years, despite the increase in brain metastases and elderly patients. This finding suggests the crucial role of novel therapies in enhancing survival outcomes.

{"title":"Evolving treatments and prognosis in Stage IV non-small cell lung cancer: 20 years of progress of novel therapies","authors":"Hironori Satoh , Yusuke Okuma , Yuki Shinno , Ken Masuda , Yuji Matsumoto , Tatsuya Yoshida , Yasushi Goto , Hidehito Horinouchi , Noboru Yamamoto , Yuichiro Ohe","doi":"10.1016/j.lungcan.2025.108453","DOIUrl":"10.1016/j.lungcan.2025.108453","url":null,"abstract":"<div><h3>Background</h3><div>Advancements in pharmacotherapy, including molecular targeted therapies and immune checkpoint inhibitors, have revolutionized the treatment for Stage IV non-small cell lung cancer (NSCLC) over the past two decades. However, differences in drug approval timelines across countries raise important questions about their impact on survival rates. This study investigates trends in overall survival (OS), patient characteristics, and the association between OS improvements and the introduction of new drugs.</div></div><div><h3>Patients and methods</h3><div>This retrospective review included patients with Stage IV NSCLC treated at the National Cancer Center Hospital in Japan from 2001 to 2021. Using data from the Department of Thoracic Oncology registries, 2,555 patients were identified and categorized into four time periods: 2001–2005 (Group A), 2006–2010 (Group B), 2011–2015 (Group C), and 2016–2021 (Group D).</div></div><div><h3>Results</h3><div>While baseline characteristics remained relatively consistent, Group D had an increased proportion of elderly patients (≥ 75 years) and those with brain metastases. Additionally, the gender ratio became more balanced over time. Notably, Group D patients with <em>EGFR</em> mutations or <em>ALK</em> fusion positivity and older age demonstrated significantly longer OS. Analysis revealed steady and substantial improvements in OS across time periods (median OS: Group A, 10.68 months; Group B, 14.12 months; Group C, 16.49 months; and Group D, 25.46 months, <strong>respectively</strong>).</div></div><div><h3>Conclusions</h3><div>This study demonstrates marked improvements in survival for patients with Stage IV NSCLC, particularly in the last six years, despite the increase in brain metastases and elderly patients. This finding suggests the crucial role of novel therapies in enhancing survival outcomes.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"202 ","pages":"Article 108453"},"PeriodicalIF":4.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143507978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Site-specific follow-up strategy for surgically resected patients with NSCLC based on ten-year follow-up data

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2025-02-16 DOI: 10.1016/j.lungcan.2025.108451

Molin Zhang , Chaoqiang Deng , Fangqiu Fu , Yuan Li , Yang Zhang , Haiquan Chen

Objectives

There is currently no consensus regarding the optimal site-specific postoperative follow-up duration for patients with completely resected non-small cell lung cancer. Long-term surveillance for recurrence may lead to psychological distress or economic burdens for patients.We aimed to propose an appropriate site-specific follow-up strategy for patients with non-small cell lung cancer based on 10-year follow-up data.

Materials and methods

We analyzed recurrence patterns in 2,359 patients with non-small cell lung cancer who underwent surgical resection from 2008 to 2013. We established potential site-specific follow-up endpoints when the subsequent recurrence rates fell below 5% and proposed a corresponding follow-up strategy.

Results

With a median follow-up of 111.0 months, postoperative recurrences were observed in 985 patients (41.8 %). We identified several factors associated with site-specific recurrence recurrence patterns, including ground-glass opacity component, sex, histology type, and pathological TNM stage. No recurrence was observed in patients with pure ground-glass nodules, a consolidation-to-tumor ratio less than 0.5, or a pathological type classified as lepidic pattern-predominant adenocarcinoma. In thorax, brain and bone, patients with non-squamous cell carcinoma exhibited higher recurrence rates than those with squamous cell carcinoma. In abdomen and neck, male patients have a higher recurrence rate than female patients, particularly within the pathological stage III group.

Conclusions

The follow-up strategy was developed based on the recurrence patterns analyzed from ten-year follow-up data. The online tool may assist in determining the optimal site-specific duration for surveillance based on clinicopathologic features.

{"title":"Site-specific follow-up strategy for surgically resected patients with NSCLC based on ten-year follow-up data","authors":"Molin Zhang , Chaoqiang Deng , Fangqiu Fu , Yuan Li , Yang Zhang , Haiquan Chen","doi":"10.1016/j.lungcan.2025.108451","DOIUrl":"10.1016/j.lungcan.2025.108451","url":null,"abstract":"<div><h3>Objectives</h3><div>There is currently no consensus regarding the optimal site-specific postoperative follow-up duration for patients with completely resected non-small cell lung cancer. Long-term surveillance for recurrence may lead to psychological distress or economic burdens for patients.We aimed to propose an appropriate site-specific follow-up strategy for patients with non-small cell lung cancer based on 10-year follow-up data.</div></div><div><h3>Materials and methods</h3><div>We analyzed recurrence patterns in 2,359 patients with non-small cell lung cancer who underwent surgical resection from 2008 to 2013. We established potential site-specific follow-up endpoints when the subsequent recurrence rates fell below 5% and proposed a corresponding follow-up strategy.</div></div><div><h3>Results</h3><div>With a median follow-up of 111.0 months, postoperative recurrences were observed in 985 patients (41.8 %). We identified several factors associated with site-specific recurrence recurrence patterns, including ground-glass opacity component, sex, histology type, and pathological TNM stage. No recurrence was observed in patients with pure ground-glass nodules, a consolidation-to-tumor ratio less than 0.5, or a pathological type classified as lepidic pattern-predominant adenocarcinoma. In thorax, brain and bone, patients with non-squamous cell carcinoma exhibited higher recurrence rates than those with squamous cell carcinoma. In abdomen and neck, male patients have a higher recurrence rate than female patients, particularly within the pathological stage III group.</div></div><div><h3>Conclusions</h3><div>The follow-up strategy was developed based on the recurrence patterns analyzed from ten-year follow-up data. The online tool may assist in determining the optimal site-specific duration for surveillance based on clinicopathologic features.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"201 ","pages":"Article 108451"},"PeriodicalIF":4.5,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0