JTO Clinical and Research Reports最新文献

Acknowledgment of Reviewers

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-02-26 DOI: 10.1016/S2666-3643(25)00026-8

引用次数: 0

Durvalumab, Tremelimumab, and Platinum Chemotherapy in EGFR Mutation–Positive NSCLC: An Open-Label Phase 2 Trial (ILLUMINATE)

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-02-01 DOI: 10.1016/j.jtocrr.2024.100771

Chee Khoon Lee PhD , Bin-Chi Liao MD , Shalini Subramaniam MMed (Clin Epi) , Chao-Hua Chiu MD , Antony J. Mersiades MMed (Clin Epi) , Chao-Chi Ho MD, PhD , Chris Brown MBiostats , Chun-Liang Lai MD, PhD , Brett G.M. Hughes M.B.B.S. (Hons) , Tsung-Ying Yang MD, PhD , Ken O’Byrne MD , Yung-Hung Luo MD, PhD , Sonia Yip PhD , Ching-Liang Ho MD , Victoria Bray PhD , Wu-Chou Su MD, PhD , Melissa Moore PhD , Wei-Lien Feng MS , Ya-Ying Bai MS , Kate Ford MHSc , James Chih-Hsin Yang MD, PhD

Introduction

EGFR-mutant NSCLC is associated with low mutation burden and low levels of PD-L1 expression. We conducted a phase 2 trial to determine the efficacy of durvalumab, tremelimumab, and platinum-pemetrexed in EGFR-mutant NSCLC after progression with EGFR tyrosine kinase inhibitors (TKIs).

Methods

Participants were treated with induction durvalumab, tremelimumab, and platinum-pemetrexed, followed by durvalumab-pemetrexed maintenance. Participants were divided into two cohorts: (1) EGFR exon 20 T790M negative (T790M−, progressing on either first-line osimertinib, or on a single line of first/second generation TKI), and (2) T790M positive (T790M+, progressing on greater than or equal to 1 lines of TKI, including osimertinib). The primary endpoint was the confirmed objective response rate (ORR) assessed by the investigators. Progression-free survival and safety were secondary outcomes.

Results

One hundred participants from Australia and Taiwan were enrolled. Median follow-up was 26 months with 88% and 96% experiencing progression events for T790M− and T790M+, respectively. The ORR for T790M− was 31% (95% confidence interval: 20–45), including two complete responses. The ORR for T790M+ was 21% (95% confidence interval: 12–34). Median durations of response were 9.5 months and 6.3 months for T790M− and T790M+, respectively; median progression-free survival rates were 6.5 months and 4.9 months, respectively. For T790M−, ORR was 27% for 50% or higher PD-L1 (n = 22) and 0% for less than 50% PD-L1 (n = 10), respectively. For T790M+, ORR was 17% for 50% or higher PD-L1 (n = 24). The safety profile was consistent with previous reports.

Conclusions

Durvalumab, tremelimumab, and platinum-pemetrexed had modest anti-tumor activity in EGFR-mutant NSCLC after progression on TKI. The T790M− cohort had higher ORR and a longer duration of response. Immune adverse events were not increased with tremelimumab. The clinical registration number of this trial is NCT03994393.

{"title":"Durvalumab, Tremelimumab, and Platinum Chemotherapy in EGFR Mutation–Positive NSCLC: An Open-Label Phase 2 Trial (ILLUMINATE)","authors":"Chee Khoon Lee PhD , Bin-Chi Liao MD , Shalini Subramaniam MMed (Clin Epi) , Chao-Hua Chiu MD , Antony J. Mersiades MMed (Clin Epi) , Chao-Chi Ho MD, PhD , Chris Brown MBiostats , Chun-Liang Lai MD, PhD , Brett G.M. Hughes M.B.B.S. (Hons) , Tsung-Ying Yang MD, PhD , Ken O’Byrne MD , Yung-Hung Luo MD, PhD , Sonia Yip PhD , Ching-Liang Ho MD , Victoria Bray PhD , Wu-Chou Su MD, PhD , Melissa Moore PhD , Wei-Lien Feng MS , Ya-Ying Bai MS , Kate Ford MHSc , James Chih-Hsin Yang MD, PhD","doi":"10.1016/j.jtocrr.2024.100771","DOIUrl":"10.1016/j.jtocrr.2024.100771","url":null,"abstract":"<div><h3>Introduction</h3><div><em>EGFR</em>-mutant NSCLC is associated with low mutation burden and low levels of PD-L1 expression. We conducted a phase 2 trial to determine the efficacy of durvalumab, tremelimumab, and platinum-pemetrexed in <em>EGFR-</em>mutant NSCLC after progression with EGFR tyrosine kinase inhibitors (TKIs).</div></div><div><h3>Methods</h3><div>Participants were treated with induction durvalumab, tremelimumab, and platinum-pemetrexed, followed by durvalumab-pemetrexed maintenance. Participants were divided into two cohorts: (1) <em>EGFR</em> exon 20 T790M negative (T790M−, progressing on either first-line osimertinib, or on a single line of first/second generation TKI), and (2) T790M positive (T790M+, progressing on greater than or equal to 1 lines of TKI, including osimertinib). The primary endpoint was the confirmed objective response rate (ORR) assessed by the investigators. Progression-free survival and safety were secondary outcomes.</div></div><div><h3>Results</h3><div>One hundred participants from Australia and Taiwan were enrolled. Median follow-up was 26 months with 88% and 96% experiencing progression events for T790M− and T790M+, respectively. The ORR for T790M− was 31% (95% confidence interval: 20–45), including two complete responses. The ORR for T790M+ was 21% (95% confidence interval: 12–34). Median durations of response were 9.5 months and 6.3 months for T790M− and T790M+, respectively; median progression-free survival rates were 6.5 months and 4.9 months, respectively. For T790M−, ORR was 27% for 50% or higher PD-L1 (n = 22) and 0% for less than 50% PD-L1 (n = 10), respectively. For T790M+, ORR was 17% for 50% or higher PD-L1 (n = 24). The safety profile was consistent with previous reports.</div></div><div><h3>Conclusions</h3><div>Durvalumab, tremelimumab, and platinum-pemetrexed had modest anti-tumor activity in <em>EGFR-</em>mutant NSCLC after progression on TKI. The T790M− cohort had higher ORR and a longer duration of response. Immune adverse events were not increased with tremelimumab. The clinical registration number of this trial is NCT03994393.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 2","pages":"Article 100771"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059562","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}

引用次数: 0

Impact of Prophylactic Use of PEG-rhG-CSF on First-Line Immunochemotherapy in Advanced NSCLC: A Cohort Study

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-02-01 DOI: 10.1016/j.jtocrr.2024.100780

Li Sun MD, Yuan Tian MD, Shuling Zhang MD, PhD, Letian Huang MD, Jietao Ma MD, PhD, Chengbo Han MD, PhD

Introduction

This study aimed to assess the impact of prophylactic use of PEG-rhG-CSF on first-line immunochemotherapy in advanced NSCLC.

Methods

A cohort of patients with advanced NSCLC who received first-line immunochemotherapy at Shengjing Hospital of China Medical University between January 2019 and July 2024 was selected for this study. Patients were divided into the following two groups: a treatment group that received prophylactic PEG-rhG-CSF (≥1 cycle) 48 hours after immunochemotherapy and a control group that did not receive PEG-rhG-CSF. The primary end points were progression-free survival (PFS), overall survival (OS), overall response rate, and safety. A propensity score-matched analysis was performed to reduce potential confounders.

Results

A total of 220 patients were enrolled, with 87 in the treatment group and 133 in the control group. Median PFS was 10.5 months in both the treatment and control groups (p = 0.86), and median OS was 33.9 months in the treatment group versus not reached in the control group (p = 0.71). The overall response rate was 64.4% in the treatment group and 58.6% in the control group (p = 0.40). After propensity score-matched analysis (each group included 78 patients), median PFS was 12.6 months in the treatment group versus 10.5 months in the control group (p = 0.99), and median OS remained 30.3 months in the treatment group versus not reached in the control group (p = 0.85). The treatment group had a reduced incidence of chemotherapy interruptions, any grade of leukopenia, any grade of neutropenia, and grades 3 to 5 neutropenia, without an increase in immune-related adverse events.

Conclusions

The prophylactic use of PEG-rhG-CSF in patients with advanced NSCLC undergoing first-line immunochemotherapy did not compromise efficacy and safety. It reduced chemotherapy interruptions and neutropenia, without increasing immune-related adverse events, thus supporting safe and uninterrupted treatment.

{"title":"Impact of Prophylactic Use of PEG-rhG-CSF on First-Line Immunochemotherapy in Advanced NSCLC: A Cohort Study","authors":"Li Sun MD, Yuan Tian MD, Shuling Zhang MD, PhD, Letian Huang MD, Jietao Ma MD, PhD, Chengbo Han MD, PhD","doi":"10.1016/j.jtocrr.2024.100780","DOIUrl":"10.1016/j.jtocrr.2024.100780","url":null,"abstract":"<div><h3>Introduction</h3><div>This study aimed to assess the impact of prophylactic use of PEG-rhG-CSF on first-line immunochemotherapy in advanced NSCLC.</div></div><div><h3>Methods</h3><div>A cohort of patients with advanced NSCLC who received first-line immunochemotherapy at Shengjing Hospital of China Medical University between January 2019 and July 2024 was selected for this study. Patients were divided into the following two groups: a treatment group that received prophylactic PEG-rhG-CSF (≥1 cycle) 48 hours after immunochemotherapy and a control group that did not receive PEG-rhG-CSF. The primary end points were progression-free survival (PFS), overall survival (OS), overall response rate, and safety. A propensity score-matched analysis was performed to reduce potential confounders.</div></div><div><h3>Results</h3><div>A total of 220 patients were enrolled, with 87 in the treatment group and 133 in the control group. Median PFS was 10.5 months in both the treatment and control groups (<em>p</em> = 0.86), and median OS was 33.9 months in the treatment group versus not reached in the control group (<em>p</em> = 0.71). The overall response rate was 64.4% in the treatment group and 58.6% in the control group (<em>p</em> = 0.40). After propensity score-matched analysis (each group included 78 patients), median PFS was 12.6 months in the treatment group versus 10.5 months in the control group (<em>p</em> = 0.99), and median OS remained 30.3 months in the treatment group versus not reached in the control group (<em>p</em> = 0.85). The treatment group had a reduced incidence of chemotherapy interruptions, any grade of leukopenia, any grade of neutropenia, and grades 3 to 5 neutropenia, without an increase in immune-related adverse events.</div></div><div><h3>Conclusions</h3><div>The prophylactic use of PEG-rhG-CSF in patients with advanced NSCLC undergoing first-line immunochemotherapy did not compromise efficacy and safety. It reduced chemotherapy interruptions and neutropenia, without increasing immune-related adverse events, thus supporting safe and uninterrupted treatment.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 2","pages":"Article 100780"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059496","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}

引用次数: 0

A Response Letter to Kosaka et al. Regarding Manuscript Titled: “Radiotherapy Improves Survival in Non–Small Cell Lung Cancer Following Oligoprogression on Immunotherapy: A Cohort Study”

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-02-01 DOI: 10.1016/j.jtocrr.2024.100767

Lauren Julia Brown M.B.B.S., MClinTRes, FRACP, Julie Ahn M.B.B.S., Bo Gao BmedSci, M.B.B.S., FRACP, PhD, Harriet Gee M.B.B.S., DPhil, FRANZCR, Adnan Nagrial M.B.B.S., FRACP, PhD, Inês Pires da Silva MD, FRACP, PhD, Eric Hau BSc (Med), M.B.B.S., Grad Cert (Biostat), FRANZCR, PHD

引用次数: 0

Afatinib and Necitumumab in EGFR-Mutant NSCLC with Acquired Resistance to Tyrosine Kinase Inhibitors

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-02-01 DOI: 10.1016/j.jtocrr.2024.100757

Nathaniel J. Myall MD , Jennifer G. Whisenant PhD , Joel W. Neal MD, PhD , Wade T. Iams MD , Karen L. Reckamp MD , Sally York MD, PhD , Lynne D. Berry PhD , Yu Shyr PhD , Leora Horn MD , Heather A. Wakelee MD , Sukhmani K. Padda MD

Introduction

Although tyrosine kinase inhibitors (TKIs) are effective against NSCLC harboring sensitizing EGFR gene mutations, acquired resistance is inevitable. Preclinical studies suggest that combining EGFR TKI and monoclonal antibody therapies may have activity in EGFR-mutated NSCLC that has progressed on TKI therapy alone. Therefore, we prospectively evaluated afatinib plus necitumumab in patients with EGFR-mutated NSCLC.

Methods

This was a phase 1, dose-escalation, dose-expansion trial assessing the safety and efficacy of afatinib plus necitumumab. Patients had advanced or metastatic EGFR-mutated NSCLC with progression after (1) first-generation TKI if T790M negative, (2) subsequent line third-generation TKI if T790M positive, or (3) third-generation TKI in the first-line setting. Dose-escalation followed a 3+3 design. The primary end point of dose-expansion was objective response rate.

Results

A total of 22 patients with EGFR-mutated NSCLC were enrolled. The maximum tolerated dose was afatinib 40 mg oral daily plus necitumumab 600 mg intravenous on days 1 and 15 every 28 days. There were no grade 4 to 5 adverse events observed, and seven patients (32%) experienced grade 3 treatment-related adverse events (three rash; one each oral mucositis, diarrhea, headache, ventricular arrhythmia, and tachycardia). In the entire cohort, there were no responses observed, the median progression-free survival was 1.8 months, and the disease control rate was 36% but varied between the subgroups.

Conclusions

Afatinib plus necitumumab was safe but had limited activity in patients with EGFR-mutated NSCLC. Biomarker studies may identify patient subgroups that are more likely to benefit.

{"title":"Afatinib and Necitumumab in EGFR-Mutant NSCLC with Acquired Resistance to Tyrosine Kinase Inhibitors","authors":"Nathaniel J. Myall MD , Jennifer G. Whisenant PhD , Joel W. Neal MD, PhD , Wade T. Iams MD , Karen L. Reckamp MD , Sally York MD, PhD , Lynne D. Berry PhD , Yu Shyr PhD , Leora Horn MD , Heather A. Wakelee MD , Sukhmani K. Padda MD","doi":"10.1016/j.jtocrr.2024.100757","DOIUrl":"10.1016/j.jtocrr.2024.100757","url":null,"abstract":"<div><h3>Introduction</h3><div>Although tyrosine kinase inhibitors (TKIs) are effective against NSCLC harboring sensitizing <em>EGFR</em> gene mutations, acquired resistance is inevitable. Preclinical studies suggest that combining EGFR TKI and monoclonal antibody therapies may have activity in <em>EGFR-</em>mutated NSCLC that has progressed on TKI therapy alone. Therefore, we prospectively evaluated afatinib plus necitumumab in patients with <em>EGFR-</em>mutated NSCLC.</div></div><div><h3>Methods</h3><div>This was a phase 1, dose-escalation, dose-expansion trial assessing the safety and efficacy of afatinib plus necitumumab. Patients had advanced or metastatic <em>EGFR-</em>mutated NSCLC with progression after (1) first-generation TKI if T790M negative, (2) subsequent line third-generation TKI if T790M positive, or (3) third-generation TKI in the first-line setting. Dose-escalation followed a 3+3 design. The primary end point of dose-expansion was objective response rate.</div></div><div><h3>Results</h3><div>A total of 22 patients with <em>EGFR</em>-mutated NSCLC were enrolled. The maximum tolerated dose was afatinib 40 mg oral daily plus necitumumab 600 mg intravenous on days 1 and 15 every 28 days. There were no grade 4 to 5 adverse events observed, and seven patients (32%) experienced grade 3 treatment-related adverse events (three rash; one each oral mucositis, diarrhea, headache, ventricular arrhythmia, and tachycardia). In the entire cohort, there were no responses observed, the median progression-free survival was 1.8 months, and the disease control rate was 36% but varied between the subgroups.</div></div><div><h3>Conclusions</h3><div>Afatinib plus necitumumab was safe but had limited activity in patients with <em>EGFR-</em>mutated NSCLC. Biomarker studies may identify patient subgroups that are more likely to benefit.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 2","pages":"Article 100757"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046289","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}

引用次数: 0

EGFR-Mutated Lung Adenocarcinoma With Li–Fraumeni Syndrome: The Imperative for Germline Testing in Patients With a Family History, a Case Report 表皮生长因子受体突变肺腺癌伴 Li-Fraumeni 综合征：有家族史的患者必须进行基因检测，病例报告

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-02-01 DOI: 10.1016/j.jtocrr.2024.100691

Hiroyuki Fujii MD , Yusuke Okuma MD, PhD , Makoto Hirata MD, PhD , Yuki Shinno MD, PhD , Tatsuya Yoshida MD, PhD , Yasushi Goto MD, PhD , Hidehito Horinouchi MD, PhD , Noboru Yamamoto MD, PhD , Yuichiro Ohe MD, PhD

Comprehensive genomic profiling (CGP) has progressed rapidly and plays an important role in advancing precision medicine in oncology. However, CGP provides opportunities for molecular-targeted therapy, but it also unveils incidental germline findings, posing challenges and opportunities in patient care.

We present the case of a 32-year-old female patient, diagnosed with stage IVB lung adenocarcinoma harboring an EGFR p.L746_A750del, who was also subsequently diagnosed with Li–Fraumeni syndrome (LFS) through CGP testing. Remarkably, despite the presence of EGFR mutation, the response to EGFR-tyrosine kinase inhibitor was poor, whereas the response to cytotoxic anticancer drugs and immunotherapy was favorable. After the diagnosis of LFS, she underwent genetic counseling and has been screened for the development of a second cancer based on the Toronto protocol.

This case highlights the importance of family history interviews and considering the practice of germline genomic testing for optimal management of lung cancer patients with a hereditary cancer syndrome such as LFS. Further research is warranted to delineate the impact of germline variants on treatment outcomes and secondary cancer prevention in lung cancer.

{"title":"EGFR-Mutated Lung Adenocarcinoma With Li–Fraumeni Syndrome: The Imperative for Germline Testing in Patients With a Family History, a Case Report","authors":"Hiroyuki Fujii MD , Yusuke Okuma MD, PhD , Makoto Hirata MD, PhD , Yuki Shinno MD, PhD , Tatsuya Yoshida MD, PhD , Yasushi Goto MD, PhD , Hidehito Horinouchi MD, PhD , Noboru Yamamoto MD, PhD , Yuichiro Ohe MD, PhD","doi":"10.1016/j.jtocrr.2024.100691","DOIUrl":"10.1016/j.jtocrr.2024.100691","url":null,"abstract":"<div><div>Comprehensive genomic profiling (CGP) has progressed rapidly and plays an important role in advancing precision medicine in oncology. However, CGP provides opportunities for molecular-targeted therapy, but it also unveils incidental germline findings, posing challenges and opportunities in patient care.</div><div>We present the case of a 32-year-old female patient, diagnosed with stage IVB lung adenocarcinoma harboring an <em>EGFR</em> p.L746_A750del, who was also subsequently diagnosed with Li–Fraumeni syndrome (LFS) through CGP testing. Remarkably, despite the presence of <em>EGFR</em> mutation, the response to EGFR-tyrosine kinase inhibitor was poor, whereas the response to cytotoxic anticancer drugs and immunotherapy was favorable. After the diagnosis of LFS, she underwent genetic counseling and has been screened for the development of a second cancer based on the Toronto protocol.</div><div>This case highlights the importance of family history interviews and considering the practice of germline genomic testing for optimal management of lung cancer patients with a hereditary cancer syndrome such as LFS. Further research is warranted to delineate the impact of germline variants on treatment outcomes and secondary cancer prevention in lung cancer.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 2","pages":"Article 100691"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141026230","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}

引用次数: 0

Next-Generation Sequencing Analysis on Image-Guided Biopsy Samples in Early-Stage Lung Cancer: Feasibility Study and Comparison With Surgical Samples

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-02-01 DOI: 10.1016/j.jtocrr.2024.100777

Louis Gros MD, Rowena Yip PhD, MPH, Arel Golombeck MD, David F. Yankelevitz MD, Claudia I. Henschke PhD, MD

Introduction

Limited information exists on next-generation sequencing (NGS) success for lung tumors of 30 mm or less. We aimed to compare NGS success rates across biopsy techniques for these tumors, assess DNA sequencing quality, and verify reliability against surgical resection results.

Methods

We used data from the Initiative for Early Lung Cancer Research on Treatment study, including patients with lung tumors measuring 30 mm or less who had surgery and NGS on biopsies since 2016. We collected data on biopsy type, nodule characteristics, complications, sequencing feasibility, clinical actionable variants, surgery type, and TNM classification. We compared NGS feasibility and quality between biopsy methods and, for those with NGS on surgical samples, compared feasibility, quality, and detection of actionable variants.

Results

Among the 654 participants with lung tumors of 30 mm or less who underwent surgery, 70 had NGS on prior biopsies. The median age was 68.5; 51.4% were male individuals, and 75.7% were smokers. The mean diameter of biopsied nodules was 17.7 mm, with 67.1% fine-needle aspiration, 17.1% computed tomography–guided transthoracic core needle biopsies, and 17.1% endobronchial ultrasound–guided transbronchial needle aspiration. DNA sequencing was feasible in 97.1% of biopsy samples; 2.9% had low tumor cellularity. Coverage depth was achieved in 89.7% of biopsies. RNA sequencing was successful in 66.2% of biopsies, especially in core needle biopsies. Actionable alterations were found in 41.4% of patients. Among the participants, 30% had NGS on surgical samples. RNA sequencing was more feasible on surgical samples (95.2% versus 42.9% for biopsies). NGS on surgical samples matched biopsy results in 90% of patients, with 10% showing additional alterations.

Conclusion

DNA sequencing succeeded in 97.1% of biopsies of nodules 30 mm or less, whereas RNA sequencing feasibility was lower. NGS on biopsy samples is generally reliable but requires careful review.

{"title":"Next-Generation Sequencing Analysis on Image-Guided Biopsy Samples in Early-Stage Lung Cancer: Feasibility Study and Comparison With Surgical Samples","authors":"Louis Gros MD, Rowena Yip PhD, MPH, Arel Golombeck MD, David F. Yankelevitz MD, Claudia I. Henschke PhD, MD","doi":"10.1016/j.jtocrr.2024.100777","DOIUrl":"10.1016/j.jtocrr.2024.100777","url":null,"abstract":"<div><h3>Introduction</h3><div>Limited information exists on next-generation sequencing (NGS) success for lung tumors of 30 mm or less. We aimed to compare NGS success rates across biopsy techniques for these tumors, assess DNA sequencing quality, and verify reliability against surgical resection results.</div></div><div><h3>Methods</h3><div>We used data from the Initiative for Early Lung Cancer Research on Treatment study, including patients with lung tumors measuring 30 mm or less who had surgery and NGS on biopsies since 2016. We collected data on biopsy type, nodule characteristics, complications, sequencing feasibility, clinical actionable variants, surgery type, and TNM classification. We compared NGS feasibility and quality between biopsy methods and, for those with NGS on surgical samples, compared feasibility, quality, and detection of actionable variants.</div></div><div><h3>Results</h3><div>Among the 654 participants with lung tumors of 30 mm or less who underwent surgery, 70 had NGS on prior biopsies. The median age was 68.5; 51.4% were male individuals, and 75.7% were smokers. The mean diameter of biopsied nodules was 17.7 mm, with 67.1% fine-needle aspiration, 17.1% computed tomography–guided transthoracic core needle biopsies, and 17.1% endobronchial ultrasound–guided transbronchial needle aspiration. DNA sequencing was feasible in 97.1% of biopsy samples; 2.9% had low tumor cellularity. Coverage depth was achieved in 89.7% of biopsies. RNA sequencing was successful in 66.2% of biopsies, especially in core needle biopsies. Actionable alterations were found in 41.4% of patients. Among the participants, 30% had NGS on surgical samples. RNA sequencing was more feasible on surgical samples (95.2% versus 42.9% for biopsies). NGS on surgical samples matched biopsy results in 90% of patients, with 10% showing additional alterations.</div></div><div><h3>Conclusion</h3><div>DNA sequencing succeeded in 97.1% of biopsies of nodules 30 mm or less, whereas RNA sequencing feasibility was lower. NGS on biopsy samples is generally reliable but requires careful review.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 2","pages":"Article 100777"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059497","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}

引用次数: 0

Epidemiology of SCLC in the United States From 2000 to 2019: A Study Utilizing the Surveillance, Epidemiology, and End Results Registry

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-01-20 DOI: 10.1016/j.jtocrr.2025.100799

Leah E. Wells MD , Sean Cohen MD , Benjamin Brennan MS , Mousumi Banerjee PhD , Gregory P. Kalemkerian MD

Introduction

From the late 1980s to 2000, SCLC represented a decreasing proportion of lung cancer cases in the United States. Nevertheless, survival outcomes in SCLC did not improve, reflecting the paucity of treatment advances. We sought to determine whether these trends continued into more recent decades, before the Food and Drug Administration approval of immunotherapy for SCLC in 2019, by evaluating the incidence and survival of SCLC from 2000 to 2019 in the United States population, with attention to variance across gender and racial subgroups.

Methods

Using the United States Surveillance, Epidemiology, and End Results 17 database, we evaluated the incidence of SCLC and NSCLC from 2000 to 2019. Demographic, staging, and survival data were collected for patients with SCLC by comparing the incidence and outcomes across groups.

Results

The percentage of SCLC among all newly diagnosed lung cancer cases decreased from 14.5% in 2000 to 11.8% in 2019. A decrease in SCLC incidence was observed in all sex and racial subgroups but was earlier and steeper in men than in women. This has resulted in a shift in the male-to-female ratio from 1.14:1 in 2000 to 0.93:1 in 2019. Among the racial subgroups, the incidence of SCLC declined most slowly in non-Hispanic Whites and most rapidly in non-Hispanic Asians and Pacific Islanders. There was a decline in limited-stage SCLC at diagnosis, from 31.1% in 2000 to 26.4% in 2019. Minimal improvement was observed in survival regardless of patient characteristics or stage.

Conclusions

In the preimmunotherapy era of 2000 to 2019, the incidence of SCLC continued to decline in both sexes and all racial subgroups. The male-to-female ratio continued to narrow with women outnumbering men in the most recent years. The proportion of patients with limited-stage disease continues to decline, likely because of improved staging procedures. The outcomes improved slightly but remained poor, highlighting the need for more effective treatment strategies.

{"title":"Epidemiology of SCLC in the United States From 2000 to 2019: A Study Utilizing the Surveillance, Epidemiology, and End Results Registry","authors":"Leah E. Wells MD , Sean Cohen MD , Benjamin Brennan MS , Mousumi Banerjee PhD , Gregory P. Kalemkerian MD","doi":"10.1016/j.jtocrr.2025.100799","DOIUrl":"10.1016/j.jtocrr.2025.100799","url":null,"abstract":"<div><h3>Introduction</h3><div>From the late 1980s to 2000, SCLC represented a decreasing proportion of lung cancer cases in the United States. Nevertheless, survival outcomes in SCLC did not improve, reflecting the paucity of treatment advances. We sought to determine whether these trends continued into more recent decades, before the Food and Drug Administration approval of immunotherapy for SCLC in 2019, by evaluating the incidence and survival of SCLC from 2000 to 2019 in the United States population, with attention to variance across gender and racial subgroups.</div></div><div><h3>Methods</h3><div>Using the United States Surveillance, Epidemiology, and End Results 17 database, we evaluated the incidence of SCLC and NSCLC from 2000 to 2019. Demographic, staging, and survival data were collected for patients with SCLC by comparing the incidence and outcomes across groups.</div></div><div><h3>Results</h3><div>The percentage of SCLC among all newly diagnosed lung cancer cases decreased from 14.5% in 2000 to 11.8% in 2019. A decrease in SCLC incidence was observed in all sex and racial subgroups but was earlier and steeper in men than in women. This has resulted in a shift in the male-to-female ratio from 1.14:1 in 2000 to 0.93:1 in 2019. Among the racial subgroups, the incidence of SCLC declined most slowly in non-Hispanic Whites and most rapidly in non-Hispanic Asians and Pacific Islanders. There was a decline in limited-stage SCLC at diagnosis, from 31.1% in 2000 to 26.4% in 2019. Minimal improvement was observed in survival regardless of patient characteristics or stage.</div></div><div><h3>Conclusions</h3><div>In the preimmunotherapy era of 2000 to 2019, the incidence of SCLC continued to decline in both sexes and all racial subgroups. The male-to-female ratio continued to narrow with women outnumbering men in the most recent years. The proportion of patients with limited-stage disease continues to decline, likely because of improved staging procedures. The outcomes improved slightly but remained poor, highlighting the need for more effective treatment strategies.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 4","pages":"Article 100799"},"PeriodicalIF":3.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508095","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}

引用次数: 0

Automated Measurement of Coronary Artery Calcifications and Routine Perioperative Blood Tests Predict Survival in Resected Stage I Lung Cancer

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-01-08 DOI: 10.1016/j.jtocrr.2025.100788

Federica Sabia MSc , Camilla Valsecchi MSc , Roberta Eufrasia Ledda MD , Giorgio Bogani MD , Riccardo Orlandi MD , Luigi Rolli MD , Michele Ferrari MD , Maurizio Balbi MD , Alfonso Marchianò MD , Ugo Pastorino MD

Introduction

Coronary artery calcification (CAC) is a well-known cardiovascular risk factor. In the past year, the CAC score has been investigated in lung cancer (LC) screening, suggesting promising results in terms of mortality risk assessment. Nevertheless, its role in patients with LC is still to be investigated. This study aimed to evaluate the performance of a fully automated CAC scoring alone and combined with a prognostic index on the basis of perioperative routine blood tests in predicting 5-year survival of patients with stage I LC.

Methods

This study included 536 consecutive patients with stage I LC who underwent preoperative chest computed tomography followed by surgical resection. The CAC score was measured by commercially available, fully automated artificial intelligence software. The primary outcome was the 5-year overall survival rate.

Results

A total of 110 patients (20.5%) had a CAC score greater than or equal to 400, 149 (27.8%) between 100 and 399, and 277 (51.7%) had less than 100. Male smokers had the highest CAC values: 32% compared with only 17% of nonsmokers. Females had lower CAC values compared with males both in smokers and nonsmokers: CAC greater than or equal to 400 only for 10% of smoking females and 0% in nonsmoking females. The 5-year survival was 80.3% overall, 84.7% in CAC less than 100, 77.5% in CAC 100 to 399, and 73.5% in CAC greater than or equal to 400 (p = 0.0047).

Conclusions

We observed that the CAC score predicted the 5-year overall survival in patients with resected stage I LC, both alone and combined with the modified routine blood test score. These results open new prospects for the prevention of noncancer mortality in patients with early-stage LC.

{"title":"Automated Measurement of Coronary Artery Calcifications and Routine Perioperative Blood Tests Predict Survival in Resected Stage I Lung Cancer","authors":"Federica Sabia MSc , Camilla Valsecchi MSc , Roberta Eufrasia Ledda MD , Giorgio Bogani MD , Riccardo Orlandi MD , Luigi Rolli MD , Michele Ferrari MD , Maurizio Balbi MD , Alfonso Marchianò MD , Ugo Pastorino MD","doi":"10.1016/j.jtocrr.2025.100788","DOIUrl":"10.1016/j.jtocrr.2025.100788","url":null,"abstract":"<div><h3>Introduction</h3><div>Coronary artery calcification (CAC) is a well-known cardiovascular risk factor. In the past year, the CAC score has been investigated in lung cancer (LC) screening, suggesting promising results in terms of mortality risk assessment. Nevertheless, its role in patients with LC is still to be investigated. This study aimed to evaluate the performance of a fully automated CAC scoring alone and combined with a prognostic index on the basis of perioperative routine blood tests in predicting 5-year survival of patients with stage I LC.</div></div><div><h3>Methods</h3><div>This study included 536 consecutive patients with stage I LC who underwent preoperative chest computed tomography followed by surgical resection. The CAC score was measured by commercially available, fully automated artificial intelligence software. The primary outcome was the 5-year overall survival rate.</div></div><div><h3>Results</h3><div>A total of 110 patients (20.5%) had a CAC score greater than or equal to 400, 149 (27.8%) between 100 and 399, and 277 (51.7%) had less than 100. Male smokers had the highest CAC values: 32% compared with only 17% of nonsmokers. Females had lower CAC values compared with males both in smokers and nonsmokers: CAC greater than or equal to 400 only for 10% of smoking females and 0% in nonsmoking females. The 5-year survival was 80.3% overall, 84.7% in CAC less than 100, 77.5% in CAC 100 to 399, and 73.5% in CAC greater than or equal to 400 (<em>p</em> = 0.0047).</div></div><div><h3>Conclusions</h3><div>We observed that the CAC score predicted the 5-year overall survival in patients with resected stage I LC, both alone and combined with the modified routine blood test score. These results open new prospects for the prevention of noncancer mortality in patients with early-stage LC.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 3","pages":"Article 100788"},"PeriodicalIF":3.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143173714","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}

引用次数: 0

Temporal Trends in the Utilization and Survival Outcomes of Lobar, Segmental, and Wedge Resection for Early-Stage NSCLC, 2004 to 2020

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2025-01-08 DOI: 10.1016/j.jtocrr.2025.100794

Eden Z. Deng BS , Xiaofei Wang PhD , Jianrong Zhang MD, MPH , Thomas E. Stinchcombe MD , Chi-Fu (Jeffrey) Yang MD , Nasser Altorki MD

Introduction

Although lobectomy has long been the standard of surgical treatment for early-stage NSCLC, segmental and wedge resections have become another option often used over the past two decades.

Methods

To examine the trends over time in the utilization, quality, and overall survival (OS) differences of lobectomy, segmentectomy, and wedge resection, we performed an observational, population-level study of 76,466 patients with T1 or T2 N0M0 NSCLC tumors 2 cm or less in size in the National Cancer Database, from 2004 to 2020. To compare the OS of the three treatments, we used inverse probability of treatment weighting to analyze a subgroup of cases with nodal examination and minimal comorbidity burden.

Results

From 2004 to 2020, the use of lobectomy decreased from 75.2% to 67.6% of resections, wedge remained relatively stable (20.5%–22.8%), and segmentectomy increased from 4.3% to 9.7%. The likelihood of nodal assessments and negative margins has increased for all treatments. Younger patients, patients with low comorbidity burden, and patients with smaller tumors have become increasingly likely to receive segmental and wedge resections. Five-year OS of segmentectomy (80.6%, 95% confidence interval [CI]: 78.1%–83.2%) remained noninferior to lobectomy (83.6%, 95% CI: 83.1%–84.1%]), whereas wedge resection was inferior until 2016 to 2019 (five-y OS = 79.9%, 95% CI: 75.9%–83.8%).

Conclusions

Sublobar resections, particularly segmentectomies, have increased in frequency and quality. The growing use of sublobar resections for younger and healthier patients highlights the need for additional clinical evidence demonstrating whether these trends do indeed lead to better outcomes.

{"title":"Temporal Trends in the Utilization and Survival Outcomes of Lobar, Segmental, and Wedge Resection for Early-Stage NSCLC, 2004 to 2020","authors":"Eden Z. Deng BS , Xiaofei Wang PhD , Jianrong Zhang MD, MPH , Thomas E. Stinchcombe MD , Chi-Fu (Jeffrey) Yang MD , Nasser Altorki MD","doi":"10.1016/j.jtocrr.2025.100794","DOIUrl":"10.1016/j.jtocrr.2025.100794","url":null,"abstract":"<div><h3>Introduction</h3><div>Although lobectomy has long been the standard of surgical treatment for early-stage NSCLC, segmental and wedge resections have become another option often used over the past two decades.</div></div><div><h3>Methods</h3><div>To examine the trends over time in the utilization, quality, and overall survival (OS) differences of lobectomy, segmentectomy, and wedge resection, we performed an observational, population-level study of 76,466 patients with T1 or T2 N0M0 NSCLC tumors 2 cm or less in size in the National Cancer Database, from 2004 to 2020. To compare the OS of the three treatments, we used inverse probability of treatment weighting to analyze a subgroup of cases with nodal examination and minimal comorbidity burden.</div></div><div><h3>Results</h3><div>From 2004 to 2020, the use of lobectomy decreased from 75.2% to 67.6% of resections, wedge remained relatively stable (20.5%–22.8%), and segmentectomy increased from 4.3% to 9.7%. The likelihood of nodal assessments and negative margins has increased for all treatments. Younger patients, patients with low comorbidity burden, and patients with smaller tumors have become increasingly likely to receive segmental and wedge resections. Five-year OS of segmentectomy (80.6%, 95% confidence interval [CI]: 78.1%–83.2%) remained noninferior to lobectomy (83.6%, 95% CI: 83.1%–84.1%]), whereas wedge resection was inferior until 2016 to 2019 (five-y OS = 79.9%, 95% CI: 75.9%–83.8%).</div></div><div><h3>Conclusions</h3><div>Sublobar resections, particularly segmentectomies, have increased in frequency and quality. The growing use of sublobar resections for younger and healthier patients highlights the need for additional clinical evidence demonstrating whether these trends do indeed lead to better outcomes.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 3","pages":"Article 100794"},"PeriodicalIF":3.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143348352","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}

引用次数: 0