Pub Date : 2024-11-19DOI: 10.1016/j.lungcan.2024.108034
A. John , D.J. McMahon , D. Chauhan , S. Mullings , N. Samuel , F. Kalofonou , C. Milner-Watts , N. Tokaca , N. Yousaf , M. Davidson , J. Bhosle , A. Minchom , O’Brien MER , S. Popat
Objectives
The objective of our study was to benchmark the incidence and severity of lorlatinib-related weight gain and dyslipidaemia in a real-world context, to guide future therapeutic strategies to mitigate these toxicities.
Methods
We conducted a retrospective, observational analysis of patients with ALK and ROS1-positive NSCLC at a single institution in the UK who were commenced on lorlatinib from 11/2016 to 11/2022. Non-small cell lung cancer (NSCLC) patients prescribed lorlatinib were identified through institutional electronic pharmacy records. Descriptive analyses were conducted. Patients without recorded baseline weight were excluded from the analysis. Changes in weight, body mass index (BMI), triglycerides, and total/low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol were calculated from serial measurements and graded in accordance with CTCAE v5.0.
Results
43 patients were evaluated. 81 % of patients developed weight gain on lorlatinib (median: 4.5 kg, 6.5 % increase from baseline); Grade < 1 in 37 % (n = 16/43), Grade 1 in 23 % (n = 10/43), Grade 2 in 12 % (n = 5/43), and Grade ≥ 3 in 9 % (n = 4/43). BMI increase was observed in 79 % of patients. 35 % of patients with healthy baseline BMI moved into overweight/obese categories.
Of patients with recorded baseline lipid levels, 91 % developed increase in total cholesterol, and 68 % an increase in triglycerides, respectively. 7 % (n = 1/15) patients with normal baseline total cholesterol developed Grade ≥ 3 elevated cholesterol; no patients with normal baseline triglycerides developed Grade ≥ 3 elevated hypertriglyceridaemia (n = 12). Median time to onset of total cholesterol elevation was 21 days. Lipid-lowering therapy was required in most patients (86 %). One patient developed a non-ST elevation myocardial infarction (NSTEMI) which may have been attributable to lorlatinib.
Conclusion
Weight gain and dyslipidaemia are commonly observed with lorlatinib, highlighting the need for effective pharmacologic and non-pharmacologic strategies to manage these toxicities. Rates were similar to those reported in the CROWN trial. Given the 60 % 5-year progression-free survival (PFS) demonstrated in CROWN, mitigation of treatment-related toxicities is paramount to minimise impact on patient quality of life (QOL) and cancer-independent morbidity in this subgroup of NSCLC patients with favourable outcomes.
{"title":"Lorlatinib-associated weight gain and dyslipidaemia: A retrospective analysis and implications for future care","authors":"A. John , D.J. McMahon , D. Chauhan , S. Mullings , N. Samuel , F. Kalofonou , C. Milner-Watts , N. Tokaca , N. Yousaf , M. Davidson , J. Bhosle , A. Minchom , O’Brien MER , S. Popat","doi":"10.1016/j.lungcan.2024.108034","DOIUrl":"10.1016/j.lungcan.2024.108034","url":null,"abstract":"<div><h3>Objectives</h3><div>The objective of our study was to benchmark the incidence and severity of lorlatinib-related weight gain and dyslipidaemia in a real-world context, to guide future therapeutic strategies to mitigate these toxicities.</div></div><div><h3>Methods</h3><div>We conducted a retrospective, observational analysis of patients with <em>ALK</em> and <em>ROS1</em>-positive NSCLC at a single institution in the UK who were commenced on lorlatinib from 11/2016 to 11/2022. Non-small cell lung cancer (NSCLC) patients prescribed lorlatinib were identified through institutional electronic pharmacy records. Descriptive analyses were conducted. Patients without recorded baseline weight were excluded from the analysis. Changes in weight, body mass index (BMI), triglycerides, and total/low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol were calculated from serial measurements and graded in accordance with CTCAE v5.0.</div></div><div><h3>Results</h3><div>43 patients were evaluated. 81 % of patients developed weight gain on lorlatinib (median: 4.5 kg, 6.5 % increase from baseline); Grade < 1 in 37 % (<em>n</em> = 16/43), Grade 1 in 23 % (<em>n</em> = 10/43), Grade 2 in 12 % (<em>n</em> = 5/43), and Grade ≥ 3 in 9 % (<em>n</em> = 4/43). BMI increase was observed in 79 % of patients. 35 % of patients with healthy baseline BMI moved into overweight/obese categories.</div><div>Of patients with recorded baseline lipid levels, 91 % developed increase in total cholesterol, and 68 % an increase in triglycerides, respectively. 7 % (<em>n</em> = 1/15) patients with normal baseline total cholesterol developed Grade ≥ 3 elevated cholesterol; no patients with normal baseline triglycerides developed Grade ≥ 3 elevated hypertriglyceridaemia (<em>n</em> = 12). Median time to onset of total cholesterol elevation was 21 days. Lipid-lowering therapy was required in most patients (86 %). One patient developed a non-ST elevation myocardial infarction (NSTEMI) which may have been attributable to lorlatinib.</div></div><div><h3>Conclusion</h3><div>Weight gain and dyslipidaemia are commonly observed with lorlatinib, highlighting the need for effective pharmacologic and non-pharmacologic strategies to manage these toxicities. Rates were similar to those reported in the CROWN trial. Given the 60 % 5-year progression-free survival (PFS) demonstrated in CROWN, mitigation of treatment-related toxicities is paramount to minimise impact on patient quality of life (QOL) and cancer-independent morbidity in this subgroup of NSCLC patients with favourable outcomes.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"198 ","pages":"Article 108034"},"PeriodicalIF":4.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682123","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}
Pub Date : 2024-11-19DOI: 10.1016/j.lungcan.2024.108033
Zhuchen Yu , Juntao Zou , Fei Xu
Background
Lung cancer, a prevalent and deadly malignancy, is classified into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). SCLC is further subdivided into four molecular subtypes—SCLC-A, SCLC-N, SCLC-P, and SCLC-I—based on key transcription factor expression.
Methods
Immunohistochemistry (IHC) was used to assess ASCL1, NEUROD1, and POU2F3 expression in tumor tissues. The H-Score quantified these results. Clinical characteristics, overall survival (OS), progression-free survival (PFS), and treatment responses were analyzed by subtype, and sensitivity to different treatments was assessed. Risk factors were identified through univariate and multivariate analyses.
Results
IHC and H-Score analysis showed that POU2F3 expression was mutually exclusive with ASCL1 or NEUROD1. Subtype distribution was as follows: SCLC-A (40 %), SCLC-N (33 %), SCLC-P (7 %), and SCLC-I (20 %). There were no significant differences in baseline characteristics, OS (p = 0.829), or PFS (p = 0.924) among subtypes. However, the SCLC-I subtype showed a trend toward improved outcomes with platinum-based doublet chemotherapy plus immune checkpoint inhibitors. Multivariate COX regression identified M stage (HR: 1.72, 95 % CI: 1.13–2.63, p = 0.012) and bone metastasis at diagnosis (HR: 1.58, 95 % CI: 1.02–2.43, p = 0.040) as independent risk factors.
Conclusion
This study confirmed the SCLC subtyping based on key transcription factors. While no significant differences in OS and PFS among subtypes were found, the SCLC-I subtype showed potential benefit from platinum-based chemotherapy combined with immune checkpoint inhibitors. M stage and bone metastasis at diagnosis were identified as independent risk factors for SCLC.
{"title":"The molecular subtypes of small cell lung cancer defined by key transcription factors and their clinical significance","authors":"Zhuchen Yu , Juntao Zou , Fei Xu","doi":"10.1016/j.lungcan.2024.108033","DOIUrl":"10.1016/j.lungcan.2024.108033","url":null,"abstract":"<div><h3>Background</h3><div>Lung cancer, a prevalent and deadly malignancy, is classified into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). SCLC is further subdivided into four molecular subtypes—SCLC-A, SCLC-N, SCLC-P, and SCLC-I—based on key transcription factor expression.</div></div><div><h3>Methods</h3><div>Immunohistochemistry (IHC) was used to assess ASCL1, NEUROD1, and POU2F3 expression in tumor tissues. The H-Score quantified these results. Clinical characteristics, overall survival (OS), progression-free survival (PFS), and treatment responses were analyzed by subtype, and sensitivity to different treatments was assessed. Risk factors were identified through univariate and multivariate analyses.</div></div><div><h3>Results</h3><div>IHC and H-Score analysis showed that POU2F3 expression was mutually exclusive with ASCL1 or NEUROD1. Subtype distribution was as follows: SCLC-A (40 %), SCLC-N (33 %), SCLC-P (7 %), and SCLC-I (20 %). There were no significant differences in baseline characteristics, OS (p = 0.829), or PFS (p = 0.924) among subtypes. However, the SCLC-I subtype showed a trend toward improved outcomes with platinum-based doublet chemotherapy plus immune checkpoint inhibitors. Multivariate COX regression identified M stage (HR: 1.72, 95 % CI: 1.13–2.63, p = 0.012) and bone metastasis at diagnosis (HR: 1.58, 95 % CI: 1.02–2.43, p = 0.040) as independent risk factors.</div></div><div><h3>Conclusion</h3><div>This study confirmed the SCLC subtyping based on key transcription factors. While no significant differences in OS and PFS among subtypes were found, the SCLC-I subtype showed potential benefit from platinum-based chemotherapy combined with immune checkpoint inhibitors. M stage and bone metastasis at diagnosis were identified as independent risk factors for SCLC.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"198 ","pages":"Article 108033"},"PeriodicalIF":4.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687382","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}
Pub Date : 2024-11-17DOI: 10.1016/j.lungcan.2024.108030
F.W.J. Heijboer , T.A. Mulders , M. van Straten , L. Moonen , E.M. Speel , J.H. von der Thüsen , J.L. Derks , A.C. Dingemans
Introduction
After primary resection of pulmonary carcinoids, the recurrence rate is low (approximately 10 %). However, long-term radiological follow-up is generally recommended due to the risk of late recurrence. This must be weighed against risk of radiation-induced cancer, particularly in young patients.
Methods
The frequency and modality of radiological follow-up according to the ENETS, ESMO, and CommNETs-NANETS guidelines were assessed. Cumulative radiation exposure per guideline and subsequent increased lifetime cancer risk were estimated using sex- and age-dependent risk factors. Data from the Netherlands Cancer Registry (2003–2012) of adults with resected pulmonary carcinoids were used as a reference.
Results
Of 706 reference patients, 32 (4.5 %) were 18–30 years (y). After median follow-up of 127 months, none of the patients aged 18-30y at diagnosis developed recurrence. For these patients, the additional radiation exposure at the age of 40y due to follow-up ranges from 140-308 mSv following ENETS and 35–42 mSv following ESMO guidelines. The additional risk of death due to carcinogenic effects ranged from 0.7 % (male 30y) to 3.1 % (female 18y) following ENETS and 0.2 % (male) to 0.4 % (female) following ESMO guidelines.
Conclusions
Individualised, less extensive follow-up for young patients with resected carcinoids and a low risk of recurrence are worth exploring to decrease radiation exposure and the corresponding risk of cancer induction. The use of predictive biomarkers to personalise follow-up is warranted.
{"title":"Radiological follow-up in patients with resected pulmonary carcinoids: Should we reduce radiation exposure?","authors":"F.W.J. Heijboer , T.A. Mulders , M. van Straten , L. Moonen , E.M. Speel , J.H. von der Thüsen , J.L. Derks , A.C. Dingemans","doi":"10.1016/j.lungcan.2024.108030","DOIUrl":"10.1016/j.lungcan.2024.108030","url":null,"abstract":"<div><h3>Introduction</h3><div>After primary resection of pulmonary carcinoids, the recurrence rate is low (approximately 10 %). However, long-term radiological follow-up is generally recommended due to the risk of late recurrence. This must be weighed against risk of radiation-induced cancer, particularly in young patients.</div></div><div><h3>Methods</h3><div>The frequency and modality of radiological follow-up according to the ENETS, ESMO, and CommNETs-NANETS guidelines were assessed. Cumulative radiation exposure per guideline and subsequent increased lifetime cancer risk were estimated using sex- and age-dependent risk factors. Data from the Netherlands Cancer Registry (2003–2012) of adults with resected pulmonary carcinoids were used as a reference.</div></div><div><h3>Results</h3><div>Of 706 reference patients, 32 (4.5 %) were 18–30 years (y). After median follow-up of 127 months, none of the patients aged 18-30y at diagnosis developed recurrence. For these patients, the additional radiation exposure at the age of 40y due to follow-up ranges from 140-308 mSv following ENETS and 35–42 mSv following ESMO guidelines. The additional risk of death due to carcinogenic effects ranged from 0.7 % (male 30y) to 3.1 % (female 18y) following ENETS and 0.2 % (male) to 0.4 % (female) following ESMO guidelines.</div></div><div><h3>Conclusions</h3><div>Individualised, less extensive follow-up for young patients with resected carcinoids and a low risk of recurrence are worth exploring to decrease radiation exposure and the corresponding risk of cancer induction. The use of predictive biomarkers to personalise follow-up is warranted.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"198 ","pages":"Article 108030"},"PeriodicalIF":4.5,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142652703","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}
Pub Date : 2024-11-17DOI: 10.1016/j.lungcan.2024.108029
Sebastian Fernandez-Bussy , Rodrigo Funes-Ferrada , Alejandra Yu Lee-Mateus , Bryan F. Vaca-Cartagena , Alanna Barrios-Ruiz , Sofia Valdes-Camacho , Mohamed I. Ibrahim , Neal M. Patel , Britney N. Hazelett , Kelly S. Robertson , Ryan M. Chadha , David Abia-Trujillo
Introduction
Cystic and cavitary pulmonary lesions (PLs) frequently require histologic confirmation for an accurate diagnosis. Shape-sensing robotic-assisted bronchoscopy (ssRAB) with mobile cone beam computed tomography (mCBCT) offers a minimally invasive alternative to traditional biopsy techniques like CT-guided transthoracic biopsy. This study aimed to evaluate the diagnostic performance and safety of ssRAB in cystic and cavitary PLs.
Material and Methods
A retrospective study was conducted at Mayo Clinic Florida, of patients who underwent ssRAB with mCBCT for cavitary and cystic PLs from October 2020 to February 2024. Baseline clinical, demographic, lesion characteristics, and procedure-related data were collected. Diagnostic yield, accuracy, sensitivity for malignancy and complication rates were calculated while logistic models identified associations between variables and diagnostic yield.
Results
52 patients were included, 54 nodules were sampled. ssRAB provided a diagnostic yield of 83 % and a diagnostic accuracy of 83 %, with a sensitivity for malignancy of 97 % and specificity of 58 %. Pneumothorax occurred in 4 % of cases, with one requiring chest tube insertion. Nashville bleeding scale ≥ 2 occurred in 4 % of procedures. There was no significant association between lesion size, distance to chest wall, type of lesion and diagnostic yield.
Conclusion
ssRAB with mCBCT demonstrated high diagnostic yield and sensitivity for malignancy in cavitary and cystic PLs, with a low complication rate. Its ability to perform mediastinal staging in the same anesthetic event, along with its safety profile, suggests ssRAB as a valuable tool in the assessment of air-filled pulmonary lesions.
{"title":"Diagnostic performance of Shape-Sensing Robotic-Assisted bronchoscopy with mobile Cone-Beam CT for cystic and cavitary pulmonary lesions","authors":"Sebastian Fernandez-Bussy , Rodrigo Funes-Ferrada , Alejandra Yu Lee-Mateus , Bryan F. Vaca-Cartagena , Alanna Barrios-Ruiz , Sofia Valdes-Camacho , Mohamed I. Ibrahim , Neal M. Patel , Britney N. Hazelett , Kelly S. Robertson , Ryan M. Chadha , David Abia-Trujillo","doi":"10.1016/j.lungcan.2024.108029","DOIUrl":"10.1016/j.lungcan.2024.108029","url":null,"abstract":"<div><h3>Introduction</h3><div>Cystic and cavitary pulmonary lesions (PLs) frequently require histologic confirmation for an accurate diagnosis. Shape-sensing robotic-assisted bronchoscopy (ssRAB) with mobile cone beam computed tomography (mCBCT) offers a minimally invasive alternative to traditional biopsy techniques like CT-guided transthoracic biopsy. This study aimed to evaluate the diagnostic performance and safety of ssRAB in cystic and cavitary PLs.</div></div><div><h3>Material and Methods</h3><div>A retrospective study was conducted at Mayo Clinic Florida, of patients who underwent ssRAB with mCBCT for cavitary and cystic PLs from October 2020 to February 2024. Baseline clinical, demographic, lesion characteristics, and procedure-related data were collected. Diagnostic yield, accuracy, sensitivity for malignancy and complication rates were calculated while logistic models identified associations between variables and diagnostic yield.</div></div><div><h3>Results</h3><div>52 patients were included, 54 nodules were sampled. ssRAB provided a diagnostic yield of 83 % and a diagnostic accuracy of 83 %, with a sensitivity for malignancy of 97 % and specificity of 58 %. Pneumothorax occurred in 4 % of cases, with one requiring chest tube insertion. Nashville bleeding scale ≥ 2 occurred in 4 % of procedures. There was no significant association between lesion size, distance to chest wall, type of lesion and diagnostic yield.</div></div><div><h3>Conclusion</h3><div>ssRAB with mCBCT demonstrated high diagnostic yield and sensitivity for malignancy in cavitary and cystic PLs, with a low complication rate. Its ability to perform mediastinal staging in the same anesthetic event, along with its safety profile, suggests ssRAB as a valuable tool in the assessment of air-filled pulmonary lesions.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"198 ","pages":"Article 108029"},"PeriodicalIF":4.5,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693277","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}
Pub Date : 2024-11-17DOI: 10.1016/j.lungcan.2024.108026
Shayan Bahadori , Mozhdeh Hosseini
This systematic review explored the feasibility and impact of interventions using commercial activity monitors to track physical activity and health-related outcomes during lung cancer treatment. Inclusion criteria focused on studies involving commercially available activity trackers that provided monitoring feedback to lung cancer patients. The devices selected were popular models, including Fitbit, Garmin, Apple, Samsung, and Polar. Studies assessing the reliability or validity of these trackers, as well as qualitative studies, protocols, non-English publications, and those featuring non-commercial devices, were excluded. Additionally, studies incorporating physical activity with other interventions (e.g., robotic surgery) were excluded if exercise outcomes could not be analysed independently. Searches were conducted across various electronic databases, including the Cochrane Database of Systematic Reviews, CINAHL Complete®, Science Citation Index, Google Scholar, Scopus, IEEE Xplore, and PubMed, covering the period from January 2000 to November 2023. The quality of the studies was assessed using the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) and the Risk of Bias in Randomised Trials (RoB 2.0) tools. Twelve studies met the inclusion criteria, utilising commercial wearable technology for monitoring lung cancer patients over an average of 6.3 ± 4.7 weeks. A key limitation of this review was the wide variation in how interventions were implemented across studies. Yet, the interventions significantly improved daily activity levels and intensity, quality of life, psychological impact, and physical function compared to usual care. These monitors show promise in predicting, monitoring, and detecting physical activity, motivating patients, and aiding in recovery. However, limitations exist, and further evidence is needed to confirm their efficacy as primary monitoring tools in lung cancer treatment.
{"title":"Use of commercial WAMs for monitoring individual with lung cancer. A systematic review","authors":"Shayan Bahadori , Mozhdeh Hosseini","doi":"10.1016/j.lungcan.2024.108026","DOIUrl":"10.1016/j.lungcan.2024.108026","url":null,"abstract":"<div><div>This systematic review explored the feasibility and impact of interventions using commercial activity monitors to track physical activity and health-related outcomes during lung cancer treatment. Inclusion criteria focused on studies involving commercially available activity trackers that provided monitoring feedback to lung cancer patients. The devices selected were popular models, including Fitbit, Garmin, Apple, Samsung, and Polar. Studies assessing the reliability or validity of these trackers, as well as qualitative studies, protocols, non-English publications, and those featuring non-commercial devices, were excluded. Additionally, studies incorporating physical activity with other interventions (e.g., robotic surgery) were excluded if exercise outcomes could not be analysed independently. Searches were conducted across various electronic databases, including the Cochrane Database of Systematic Reviews, CINAHL Complete®, Science Citation Index, Google Scholar, Scopus, IEEE Xplore, and PubMed, covering the period from January 2000 to November 2023. The quality of the studies was assessed using the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) and the Risk of Bias in Randomised Trials (RoB 2.0) tools. Twelve studies met the inclusion criteria, utilising commercial wearable technology for monitoring lung cancer patients over an average of 6.3 ± 4.7 weeks. A key limitation of this review was the wide variation in how interventions were implemented across studies. Yet, the interventions significantly improved daily activity levels and intensity, quality of life, psychological impact, and physical function compared to usual care. These monitors show promise in predicting, monitoring, and detecting physical activity, motivating patients, and aiding in recovery. However, limitations exist, and further evidence is needed to confirm their efficacy as primary monitoring tools in lung cancer treatment.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"198 ","pages":"Article 108026"},"PeriodicalIF":4.5,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693278","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}
Pub Date : 2024-11-15DOI: 10.1016/j.lungcan.2024.108032
Oluwaseun Ayoade , Maureen E. Canavan , Giorgio Caturegli , Daniel J. Boffa
Background
Clinical trials are designed to minimize factors capable of influencing patient outcomes beyond the specific diseases and treatments being studied; however, exclusion of prior cancer (PC) patients could potentially affect the generalizability of study results. We attempted to create a real-world proxy of recent immunotherapy trials in stage III and IV Non-Small Cell Lung Cancer (NSCLC) to understand the relevance of a PC history using the National Cancer Database.
Methods
Patients diagnosed between 2017 and 2020 were stratified by the presence of a prior cancer history and propensity matched to compare receipt of immunotherapy with those who did not. We analyzed overall survival using Kaplan Meier analysis and Cox proportional hazards models.
Results
The addition of immunotherapy to a regimen of chemotherapy and radiation was associated with superior survival whether stage III NSCLC patients had a PC history (HR): 0.65 (95% CI 0.59, 0.71) or had no PC history (HR:0.69 95% CI: 0.66, 0.72). The addition of immunotherapy was also associated with superior survival for stage IV patients with a PC history (HR) 0.78 95% CI 0.72, 0.85) or without PC history (HR:0.75 95% CI: 0.73, 0.78).
Discussion
Examination of real-world outcomes of two practice-changing trial regimens found the innovative treatment approach to be superior, regardless of patient PC history. Risk for a second malignancy is a reality of improving cancer treatment, thus, to individualize treatment for patients based on their personal and tumor attributes, cancer survivors will need to be included in trials.
背景：临床试验旨在最大限度地减少可能影响患者预后的因素，而不局限于所研究的特定疾病和治疗方法；然而，排除既往癌症（PC）患者可能会影响研究结果的普遍性。我们试图利用国家癌症数据库创建一个近期 III 期和 IV 期非小细胞肺癌（NSCLC）免疫疗法试验的真实世界代理，以了解 PC 病史的相关性：2017年至2020年间确诊的患者按是否有既往癌症病史进行分层，并进行倾向匹配，以比较接受免疫疗法和未接受免疫疗法的患者。我们使用卡普兰-梅耶尔分析和考克斯比例危险模型分析了总生存率：结果：无论III期NSCLC患者有PC病史（HR）：0.65（95% CI 0.59，0.71）还是无PC病史（HR：0.69 95% CI：0.66，0.72），在化疗和放疗方案中加入免疫疗法均可提高生存率。对于有PC病史（HR：0.78 95% CI：0.72, 0.85）或无PC病史（HR：0.75 95% CI：0.73, 0.78）的IV期患者，增加免疫疗法也与较高的生存率相关：讨论：对两种改变实践的试验方案的实际治疗效果的研究发现，无论患者是否有PC病史，创新治疗方法都更胜一筹。二次恶性肿瘤的风险是改进癌症治疗的一个现实问题，因此，为了根据患者的个人和肿瘤属性对其进行个体化治疗，需要将癌症幸存者纳入试验中。
{"title":"Brief Report: Should a prior cancer history be reevaluated as an exclusion for clinical trial participation?","authors":"Oluwaseun Ayoade , Maureen E. Canavan , Giorgio Caturegli , Daniel J. Boffa","doi":"10.1016/j.lungcan.2024.108032","DOIUrl":"10.1016/j.lungcan.2024.108032","url":null,"abstract":"<div><h3>Background</h3><div>Clinical trials are designed to minimize factors capable of influencing patient outcomes beyond the specific diseases and treatments being studied; however, exclusion of prior cancer (PC) patients could potentially affect the generalizability of study results. We attempted to create a real-world proxy of recent immunotherapy trials in stage III and IV Non-Small Cell Lung Cancer (NSCLC) to understand the relevance of a PC history using the National Cancer Database.</div></div><div><h3>Methods</h3><div>Patients diagnosed between 2017 and 2020 were stratified by the presence of a prior cancer history and propensity matched to compare receipt of immunotherapy with those who did not. We analyzed overall survival using Kaplan Meier analysis and Cox proportional hazards models.</div></div><div><h3>Results</h3><div>The addition of immunotherapy to a regimen of chemotherapy and radiation was associated with superior survival whether stage III NSCLC patients had a PC history (HR): 0.65 (95% CI 0.59, 0.71) or had no PC history (HR:0.69 95% CI: 0.66, 0.72). The addition of immunotherapy was also associated with superior survival for stage IV patients with a PC history (HR) 0.78 95% CI 0.72, 0.85) or without PC history (HR:0.75 95% CI: 0.73, 0.78).</div></div><div><h3>Discussion</h3><div>Examination of real-world outcomes of two practice-changing trial regimens found the innovative treatment approach to be superior, regardless of patient PC history. Risk for a second malignancy is a reality of improving cancer treatment, thus, to individualize treatment for patients based on their personal and tumor attributes, cancer survivors will need to be included in trials.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"198 ","pages":"Article 108032"},"PeriodicalIF":4.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676368","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}
Pub Date : 2024-11-15DOI: 10.1016/j.lungcan.2024.108023
Soravis Osataphan , Muhammad Awidi , Yu Jen Jan , Krishna Gunturu , Shriram Sundararaman , Hollis Viray , Edward Frankenberger , Melissa Mariano , Lauren O’Loughlin , Andrew Piper-Vallillo , Katherine Stafford , Aleksandra Kolnick , Hind Ghazalah , Kartik Sehgal , Mary-Elizabeth Patti , Daniel Costa , Prudence Lam , Deepa Rangachari
Background
Obesity and hypercholesterolemia have been associated with better responses to ICIs in NSCLC, while type 2 diabetes (T2D) has been associated with a worse response. However, the association between glucose levels and outcomes remains unknown. This study investigated the impact of mean baseline glucose levels, T2D, dyslipidemia, and obesity on overall survival (OS) in NSCLC patients undergoing ICI therapy.
Methods
A multicenter retrospective cohort study was conducted using data from three medical centers, with locally advanced or metastatic NSCLC patients receiving ICI, regardless of treatment line or concurrent therapy. Random venous glucose levels within 4 weeks prior to ICI initiation, BMI, history of dyslipidemia, and T2D, along with OS, were assessed. Patients with BMI < 18.5 were excluded.
Results
Among 438 patients, those with the highest quartile of baseline glucose levels had significantly shorter OS compared to those in the lowest quartile (HR, 1.53; 95 % CI, 1.08 – 2.15; p-value = 0.016). This association remind consistent after adjusting for steroid use, diabetes, performance status and glucose-lowering medication use. These effects were consistently observed in subsets of patients treated with ICI monotherapy and with PD-L1 TPS ≥ 1 %.
Conclusion
Higher mean baseline glucose levels correlated with shorter survival in patients with NSCLC treated with ICIs. The divergent effects of individual metabolic syndrome components on ICI response in patients with NSCLC underscore the complexity of metabolic influences on treatment outcomes.
{"title":"Association between higher glucose levels and reduced survival in patients with non-small cell lung cancer treated with immune checkpoint inhibitors","authors":"Soravis Osataphan , Muhammad Awidi , Yu Jen Jan , Krishna Gunturu , Shriram Sundararaman , Hollis Viray , Edward Frankenberger , Melissa Mariano , Lauren O’Loughlin , Andrew Piper-Vallillo , Katherine Stafford , Aleksandra Kolnick , Hind Ghazalah , Kartik Sehgal , Mary-Elizabeth Patti , Daniel Costa , Prudence Lam , Deepa Rangachari","doi":"10.1016/j.lungcan.2024.108023","DOIUrl":"10.1016/j.lungcan.2024.108023","url":null,"abstract":"<div><h3>Background</h3><div>Obesity and hypercholesterolemia have been associated with better responses to ICIs in NSCLC, while type 2 diabetes (T2D) has been associated with a worse response. However, the association between glucose levels and outcomes remains unknown. This study investigated the impact of mean baseline glucose levels, T2D, dyslipidemia, and obesity on overall survival (OS) in NSCLC patients undergoing ICI therapy.</div></div><div><h3>Methods</h3><div>A multicenter retrospective cohort study was conducted using data from three medical centers, with locally advanced or metastatic NSCLC patients receiving ICI, regardless of treatment line or concurrent therapy. Random venous glucose levels within 4 weeks prior to ICI initiation, BMI, history of dyslipidemia, and T2D, along with OS, were assessed. Patients with BMI < 18.5 were excluded.</div></div><div><h3>Results</h3><div>Among 438 patients, those with the highest quartile of baseline glucose levels had significantly shorter OS compared to those in the lowest quartile (HR, 1.53; 95 % CI, 1.08 – 2.15; p-value = 0.016). This association remind consistent after adjusting for steroid use, diabetes, performance status and glucose-lowering medication use. These effects were consistently observed in subsets of patients treated with ICI monotherapy and with PD-L1 TPS ≥ 1 %.</div></div><div><h3>Conclusion</h3><div>Higher mean baseline glucose levels correlated with shorter survival in patients with NSCLC treated with ICIs. The divergent effects of individual metabolic syndrome components on ICI response in patients with NSCLC underscore the complexity of metabolic influences on treatment outcomes.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"198 ","pages":"Article 108023"},"PeriodicalIF":4.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687477","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}
Objectives: There is limited consensus on resectability criteria for Stage IIIA-N2 non-small cell lung cancer (NSCLC). We examined the patient characteristics, N2 status, treatment decisions, and clinical outcomes according to the treatment modality for Stage IIIA-N2 NSCLC in Japan.
Materials and methods: Patients with Stage IIIA-N2 NSCLC in Japan were consecutively registered in the SOLUTION study between 2013 and 2014. Patients were divided according to treatment (chemoradiotherapy [CRT], surgery + perioperative therapy [neoadjuvant and/or adjuvant therapy], surgery alone). Demographic characteristics, N2 status (number and morphological features), pathological information, and treatments were analyzed descriptively. Overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) were estimated using the Kaplan-Meier method.
Results: Of 227 patients registered, 133 underwent CRT, 56 underwent surgery + perioperative therapy, and 38 underwent surgery alone. The physicians reported the following reasons for unresectability for 116 of 133 CRT patients: large number of metastatic lymph nodes (70.7 %), extranodal infiltration (25.0 %), poor surgical tolerance (19.0 %), or other reasons (18.1 %). CRT was more frequently performed in patients whose lymph nodes had an infiltrative appearance (64.3 %) and was the predominant treatment in patients with multiple involved stations (discrete: 60.0 %; infiltrative: 80.4 %). Distant metastasis with/without local progression was found in 50.4 %, 50.0 %, and 36.8 % of patients in the CRT, surgery + perioperative therapy, and surgery alone groups, respectively. The respective 3-year OS and DFS/PFS rates (median values) were as follows: surgery + perioperative therapy-61.9 % (not reached) and 37.1 % (22.4 months; DFS); CRT group-42.2 % (31.9 months) and 26.8 % (12.0 months; PFS); surgery alone group-37.7 % (26.5 months) and 28.7 % (12.6 months; DFS).
Conclusion: This study has illuminated the real-world decision rules for choosing between surgical and non-surgical approaches in patients with Stage IIIA-N2 NSCLC. Our landmark data could support treatment decision making for using immune checkpoint inhibitors and targeted therapy for driver oncogenes in the perioperative therapy era.
{"title":"Real-world status of multimodal treatment of Stage IIIA-N2 non-small cell lung cancer in Japan: Results from the SOLUTION study, a non-interventional, multicenter cohort study.","authors":"Hidehito Horinouchi, Haruyasu Murakami, Hideyuki Harada, Tomotaka Sobue, Tomohiro Kato, Shinji Atagi, Toshiyuki Kozuki, Takaaki Tokito, Satoshi Oizumi, Masahiro Seike, Kadoaki Ohashi, Tadashi Mio, Takashi Sone, Chikako Iwao, Takeshi Iwane, Ryo Koto, Masahiro Tsuboi","doi":"10.1016/j.lungcan.2024.108027","DOIUrl":"https://doi.org/10.1016/j.lungcan.2024.108027","url":null,"abstract":"<p><strong>Objectives: </strong>There is limited consensus on resectability criteria for Stage IIIA-N2 non-small cell lung cancer (NSCLC). We examined the patient characteristics, N2 status, treatment decisions, and clinical outcomes according to the treatment modality for Stage IIIA-N2 NSCLC in Japan.</p><p><strong>Materials and methods: </strong>Patients with Stage IIIA-N2 NSCLC in Japan were consecutively registered in the SOLUTION study between 2013 and 2014. Patients were divided according to treatment (chemoradiotherapy [CRT], surgery + perioperative therapy [neoadjuvant and/or adjuvant therapy], surgery alone). Demographic characteristics, N2 status (number and morphological features), pathological information, and treatments were analyzed descriptively. Overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) were estimated using the Kaplan-Meier method.</p><p><strong>Results: </strong>Of 227 patients registered, 133 underwent CRT, 56 underwent surgery + perioperative therapy, and 38 underwent surgery alone. The physicians reported the following reasons for unresectability for 116 of 133 CRT patients: large number of metastatic lymph nodes (70.7 %), extranodal infiltration (25.0 %), poor surgical tolerance (19.0 %), or other reasons (18.1 %). CRT was more frequently performed in patients whose lymph nodes had an infiltrative appearance (64.3 %) and was the predominant treatment in patients with multiple involved stations (discrete: 60.0 %; infiltrative: 80.4 %). Distant metastasis with/without local progression was found in 50.4 %, 50.0 %, and 36.8 % of patients in the CRT, surgery + perioperative therapy, and surgery alone groups, respectively. The respective 3-year OS and DFS/PFS rates (median values) were as follows: surgery + perioperative therapy-61.9 % (not reached) and 37.1 % (22.4 months; DFS); CRT group-42.2 % (31.9 months) and 26.8 % (12.0 months; PFS); surgery alone group-37.7 % (26.5 months) and 28.7 % (12.6 months; DFS).</p><p><strong>Conclusion: </strong>This study has illuminated the real-world decision rules for choosing between surgical and non-surgical approaches in patients with Stage IIIA-N2 NSCLC. Our landmark data could support treatment decision making for using immune checkpoint inhibitors and targeted therapy for driver oncogenes in the perioperative therapy era.</p>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"108027"},"PeriodicalIF":4.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872516","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}
Pub Date : 2024-11-13DOI: 10.1016/j.lungcan.2024.108025
Lei Wang , Biao Song , Zheng Zhang , Bing Bo , Anwen Xiong , Lingyun Ye , Dacheng Xie , Juanjuan Li , Sha Zhao , Chenlei Cai , Shanghu Wang , Yuan Li , Qilong Song , Zhaohua Wang , Mengjie Wang , Yanan Cao , Hui Yin , Kunpeng Ji , Chunfu Fang , Shu-ting Shen , Caicun Zhou
Background
Current percutaneous transthoracic needle biopsies (PTNB) navigation systems present challenges due to additional steps and limitations on the operating environment.
Research Question
We developed a novel, registration-free navigation system for swift and precise CT-guided PTNB, eliminating the need for body surface markers and intraoperative registration. This study assesses its efficacy and safety.
Methods
A prospective study was conducted on participants aged 18–80 years prepared for PTNB at two clinical centers, from December 2021 to August 2022. The primary endpoint was the success rate of biopsies within 2 needle adjustments, and the secondary endpoint was the success rate within a single adjustment. Safety endpoints were defined by adverse events occurrence.
Results
The study included 98 patients (median age, 64 years, IQR 54–69 years, 71 men). The primary endpoint achieved a biopsy success rate of 98.98 %, and the secondary endpoint demonstrated 97.96 %. The overall success rate was 98.98 %, significantly exceeding the target value of 85 % (P < 0.0001). The median number of CT scans was 3, significantly fewer than predicted for the manual puncture scheme [3 (IQR 3–3) to 8 (IQR 6–8), P < 0.0001]. The average procedure duration was 18.0 min (IQR: 14.0–29.0 min). The most common adverse events were hemorrhage (14 instances) and pneumothorax (8 instances). Other adverse events included elevated blood pressure, hemoptysis, and other common events.
Interpretation
Our registration-free navigation system proved to be an effective and safe system for assisting percutaneous lung biopsies in clinical practice.
{"title":"Evaluating efficacy and safety of a novel registration-free CT-guided needle biopsy navigation system (RC 120): A multicenter, prospective clinical trial","authors":"Lei Wang , Biao Song , Zheng Zhang , Bing Bo , Anwen Xiong , Lingyun Ye , Dacheng Xie , Juanjuan Li , Sha Zhao , Chenlei Cai , Shanghu Wang , Yuan Li , Qilong Song , Zhaohua Wang , Mengjie Wang , Yanan Cao , Hui Yin , Kunpeng Ji , Chunfu Fang , Shu-ting Shen , Caicun Zhou","doi":"10.1016/j.lungcan.2024.108025","DOIUrl":"10.1016/j.lungcan.2024.108025","url":null,"abstract":"<div><h3>Background</h3><div>Current percutaneous transthoracic needle biopsies (PTNB) navigation systems present challenges due to additional steps and limitations on the operating environment.</div></div><div><h3>Research Question</h3><div>We developed a novel, registration-free navigation system for swift and precise CT-guided PTNB, eliminating the need for body surface markers and intraoperative registration. This study assesses its efficacy and safety.</div></div><div><h3>Methods</h3><div>A prospective study was conducted on participants aged 18–80 years prepared for PTNB at two clinical centers, from December 2021 to August 2022. The primary endpoint was the success rate of biopsies within 2 needle adjustments, and the secondary endpoint was the success rate within a single adjustment. Safety endpoints were defined by adverse events occurrence.</div></div><div><h3>Results</h3><div>The study included 98 patients (median age, 64 years, IQR 54–69 years, 71 men). The primary endpoint achieved a biopsy success rate of 98.98 %, and the secondary endpoint demonstrated 97.96 %. The overall success rate was 98.98 %, significantly exceeding the target value of 85 % (P < 0.0001). The median number of CT scans was 3, significantly fewer than predicted for the manual puncture scheme [3 (IQR 3–3) to 8 (IQR 6–8), P < 0.0001]. The average procedure duration was 18.0 min (IQR: 14.0–29.0 min). The most common adverse events were hemorrhage (14 instances) and pneumothorax (8 instances). Other adverse events included elevated blood pressure, hemoptysis, and other common events.</div></div><div><h3>Interpretation</h3><div>Our registration-free navigation system proved to be an effective and safe system for assisting percutaneous lung biopsies in clinical practice.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"198 ","pages":"Article 108025"},"PeriodicalIF":4.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648470","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}
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