Journal of the National Comprehensive Cancer Network最新文献

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Physical Activity and Dexamethasone for Cancer-Related Fatigue: A Preliminary Placebo-Controlled, Randomized, Double-Blind Trial. 身体活动和地塞米松治疗癌症相关疲劳:一项初步安慰剂对照、随机、双盲试验。
IF 14.8 2区 医学
Journal of the National Comprehensive Cancer Network Pub Date : 2025-01-07 DOI: 10.6004/jnccn.2024.7071
Sriram Yennurajalingam, Vicente Valero, Brandon G Smalgo, Michael J Overman, Aravind Dasari, Robert A Wolff, Kanwal Pratap Singh Raghav, Carlos H Barcenas, Naifa L Busaidy, Bryan Fellman, Karen Basen-Engquist, Kenneth R Hess, Debasish Tripathy, Eduardo Bruera
{"title":"Physical Activity and Dexamethasone for Cancer-Related Fatigue: A Preliminary Placebo-Controlled, Randomized, Double-Blind Trial.","authors":"Sriram Yennurajalingam, Vicente Valero, Brandon G Smalgo, Michael J Overman, Aravind Dasari, Robert A Wolff, Kanwal Pratap Singh Raghav, Carlos H Barcenas, Naifa L Busaidy, Bryan Fellman, Karen Basen-Engquist, Kenneth R Hess, Debasish Tripathy, Eduardo Bruera","doi":"10.6004/jnccn.2024.7071","DOIUrl":"10.6004/jnccn.2024.7071","url":null,"abstract":"<p><strong>Background: </strong>Physical activity (PA) and dexamethasone (Dex) when used independently have modest benefits for cancer-related fatigue (CRF) in patients with advanced cancer. In this study we aimed to determine the feasibility (adherence, safety, and satisfaction) of combining PA with Dex versus PA with placebo (PBO) for CRF, and to explore the effects of PA+Dex and PA+PBO on CRF.</p><p><strong>Patients and methods: </strong>In this phase II, randomized, double-blind controlled trial, eligible patients had advanced cancer and a CRF score of ≥4 on the Edmonton Symptom Assessment Scale (ESAS) for fatigue (0-10 scale). Patients were randomized to standardized PA for 4 weeks with either 4 mg of Dex (PA+Dex arm) or PBO (PA+PBO arm) twice daily for the first 7 days. Changes in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scores from baseline to days 8 and 29 were assessed. Other outcomes included change in quality-of-life scores.</p><p><strong>Results: </strong>A total of 64 (89%) patients were evaluable. Adherence rates for study medication, resistance exercise, and aerobic exercise were 91% and 92% (P=.15), 83% and 70.6% (P=.35), and 82.9% and 78.3% (P=.73), respectively, in the PA+Dex and PA+PBO arms. The satisfaction rates for the PA+Dex and PA+PBO arms were 98% and 79%, respectively. Median (IQR) changes in FACIT-F scores at days 8 and 29 from baseline were 9 (2 to 16; P<.001) and 5.75 (0 to 12.5; P=.015) for the PA+Dex arm, respectively, and 3.5 (-2.1 to 10; P=.054) and 6.5 (2.5 to 15.5; P=.006) for the PA+PBO arm, respectively. We found a significant treatment effect in the PA+Dex arm using exploratory linear mixed model analysis, with treatment showing an improvement of 5.63 units for FACIT-F scores (95% CI, 1.74-9.52; P=.005). We found significant improvement in Functional Assessment of Cancer Therapy-General (FACT-G), Patient-Reported Outcomes Measurement Information System-Fatigue Short Form 7a (PROMIS-Fatigue SF-7a), and Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) totals on days 8 and 29 in the PA+Dex arm. There was no significant difference in grade ≥3 adverse events between the arms (P=.36).</p><p><strong>Conclusions: </strong>Our study found that the use of combination PA+Dex and PA+PBO for CRF was feasible and associated with high rates of satisfaction, adherence to medication and PA intervention, and tolerability. CRF improvement with PA+Dex was clinically significant at days 8 and 29. Further larger studies are justified.</p><p><strong>Clinicaltrials: </strong>gov identifier: NCT03583255.</p>","PeriodicalId":17483,"journal":{"name":"Journal of the National Comprehensive Cancer Network","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950743","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
The Prognostic Role of HPV or p16INK4a Status in Penile Squamous Cell Carcinoma: A Meta-Analysis. HPV或p16INK4a在阴茎鳞状细胞癌中的预后作用:一项荟萃分析
IF 14.8 2区 医学
Journal of the National Comprehensive Cancer Network Pub Date : 2025-01-03 DOI: 10.6004/jnccn.2024.7078
Arfa Mustasam, Kevin Parza, Filip Ionescu, Keerthi Gullapalli, Mahati Paravathaneni, Youngchul Kim, Reagan E Sandstrom, Majd Al Assaad, G Daniel Grass, Peter Johnstone, Steven Eschrich, Houssein Safa, Juskaran Chadha, Gabriel Roman Souza, Jerel David, Adele Semaan, Niki M Zacharias, Curtis Pettaway, Anna R Giuliano, Philippe E Spiess, Jad Chahoud
{"title":"The Prognostic Role of HPV or p16INK4a Status in Penile Squamous Cell Carcinoma: A Meta-Analysis.","authors":"Arfa Mustasam, Kevin Parza, Filip Ionescu, Keerthi Gullapalli, Mahati Paravathaneni, Youngchul Kim, Reagan E Sandstrom, Majd Al Assaad, G Daniel Grass, Peter Johnstone, Steven Eschrich, Houssein Safa, Juskaran Chadha, Gabriel Roman Souza, Jerel David, Adele Semaan, Niki M Zacharias, Curtis Pettaway, Anna R Giuliano, Philippe E Spiess, Jad Chahoud","doi":"10.6004/jnccn.2024.7078","DOIUrl":"https://doi.org/10.6004/jnccn.2024.7078","url":null,"abstract":"<p><strong>Background: </strong>HPV infection is implicated in approximately half of global penile squamous cell carcinoma (PSCC) cases. Previous studies on HPV DNA and p16INK4a status in PSCC have yielded inconclusive prognostic findings. This meta-analysis aims to elucidate the prognostic role of HPV in PSCC by pooling data on disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS).</p><p><strong>Methods: </strong>We systematically searched Medline and Embase up to January 2023 for relevant human studies. Data from eligible publications reporting HPV DNA or p16INK4a status, along with and DFS, DSS, or OS outcomes, were extracted. A random-effects meta-analysis model was used to synthesize data, with study weights based on size and significance. The study protocol was registered with PROSPERO (CRD42019131355).</p><p><strong>Results: </strong>Out of 544 studies screened, 34 publications were included, comprising a pooled sample size of 3,944 patients. p16INK4a-positive status was associated with improved OS (hazard ratio [HR], 0.54; 95% CI, 0.39-0.75; I2=31%), DFS (HR, 0.52; 95% CI, 0.29-0.94; I2=20%), and DSS (HR, 0.34; 95% CI, 0.23-0.50; I2=18%). HPV DNA positivity was significantly associated with improved DFS (HR, 0.63; 95% CI, 0.46-0.87; I2=13%) and DSS (HR, 0.46; 95% CI, 0.29-0.75; I2=47%) but not OS (HR, 0.92; 95% CI, 0.74-1.11; I2=0%).</p><p><strong>Conclusions: </strong>This meta-analysis, comprising the largest number of patients with PSCC to date, shows a notable correlation between p16INK4a immunohistochemistry positivity and survival outcomes. These findings support the understanding that penile cancer cases not associated with HPV tend to behave more aggressively. We support p16INK4a immunohistochemistry testing as part of the initial diagnostic evaluation of patients with PSCC.</p>","PeriodicalId":17483,"journal":{"name":"Journal of the National Comprehensive Cancer Network","volume":" ","pages":"1-9"},"PeriodicalIF":14.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927172","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
Development of KRAS Inhibitors and Their Role for Metastatic Colorectal Cancer. KRAS抑制剂的发展及其在转移性结直肠癌中的作用。
IF 14.8 2区 医学
Journal of the National Comprehensive Cancer Network Pub Date : 2025-01-03 DOI: 10.6004/jnccn.2024.7067
Dustin A Deming
{"title":"Development of KRAS Inhibitors and Their Role for Metastatic Colorectal Cancer.","authors":"Dustin A Deming","doi":"10.6004/jnccn.2024.7067","DOIUrl":"10.6004/jnccn.2024.7067","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a heterogeneous group of diseases comprising several molecular subtypes. Comprehensive DNA sequencing is now standard practice to identify these subtype. Until recently, KRAS mutation status in metastatic CRC was primarily used as a biomarker to predict resistance to EGFR inhibition. However, with up to 40% of CRC cases harboring KRAS mutations, therapeutic targeting of RAS has been an area of great need. The development of KRASG12C inhibitors has led to the FDA approval of drugs for treating non-small cell lung cancer. Recently, these and other newly developed inhibitors have been investigated as monotherapies and in combination for metastatic KRASG12C-mutant CRC. This review examines the development of these inhibitors and highlights data supporting the inclusion of sotorasib and adagrasib, in combination with either panitumumab or cetuximab, in the NCCN Guidelines for CRC for the treatment of refractory metastatic disease.</p>","PeriodicalId":17483,"journal":{"name":"Journal of the National Comprehensive Cancer Network","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927167","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
NCCN Guidelines® Insights: Lung Cancer Screening, Version 1.2025. NCCN指南®见解:肺癌筛查,版本1.2025。
IF 14.8 2区 医学
Journal of the National Comprehensive Cancer Network Pub Date : 2025-01-01 DOI: 10.6004/jnccn.2025.0002
Douglas E Wood, Ella A Kazerooni, Denise R Aberle, Christine Argento, Jonathan Baines, Brian Boer, Lisa M Brown, Jessica Donington, Georgie A Eapen, J Scott Ferguson, Lifang Hou, Donald Klippenstein, Ana S Kolansky, Rohit Kumar, Lorriana E Leard, Ann N C Leung, Peter Mazzone, Robert E Merritt, Kim Norris, Mark Onaitis, Sudhakar Pipavath, Varun Puri, Dan Raz, Chakravarthy Reddy, Mary E Reid, Kim L Sandler, Jacob Sands, Matthew B Schabath, Catherine R Sears, Jamie L Studts, Lynn Tanoue, Amber L Thacker, Betty C Tong, William D Travis, Benjamin Wei, Kenneth Westover, Beth McCullough, Swathi Ramakrishnan
{"title":"NCCN Guidelines® Insights: Lung Cancer Screening, Version 1.2025.","authors":"Douglas E Wood, Ella A Kazerooni, Denise R Aberle, Christine Argento, Jonathan Baines, Brian Boer, Lisa M Brown, Jessica Donington, Georgie A Eapen, J Scott Ferguson, Lifang Hou, Donald Klippenstein, Ana S Kolansky, Rohit Kumar, Lorriana E Leard, Ann N C Leung, Peter Mazzone, Robert E Merritt, Kim Norris, Mark Onaitis, Sudhakar Pipavath, Varun Puri, Dan Raz, Chakravarthy Reddy, Mary E Reid, Kim L Sandler, Jacob Sands, Matthew B Schabath, Catherine R Sears, Jamie L Studts, Lynn Tanoue, Amber L Thacker, Betty C Tong, William D Travis, Benjamin Wei, Kenneth Westover, Beth McCullough, Swathi Ramakrishnan","doi":"10.6004/jnccn.2025.0002","DOIUrl":"https://doi.org/10.6004/jnccn.2025.0002","url":null,"abstract":"<p><p>The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Lung Cancer Screening provide criteria for selecting individuals for screening and offer recommendations for evaluating and managing lung nodules detected during initial and subsequent annual screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.</p>","PeriodicalId":17483,"journal":{"name":"Journal of the National Comprehensive Cancer Network","volume":"23 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007760","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
Changes for JNCCN in 2025. 2025年JNCCN的变化。
IF 14.8 2区 医学
Journal of the National Comprehensive Cancer Network Pub Date : 2025-01-01 DOI: 10.6004/jnccn.2025.0003
Daniel M Geynisman
{"title":"Changes for JNCCN in 2025.","authors":"Daniel M Geynisman","doi":"10.6004/jnccn.2025.0003","DOIUrl":"https://doi.org/10.6004/jnccn.2025.0003","url":null,"abstract":"","PeriodicalId":17483,"journal":{"name":"Journal of the National Comprehensive Cancer Network","volume":"23 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007758","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
Dermatofibrosarcoma Protuberans, Version 1.2025, NCCN Clinical Practice Guidelines In Oncology. 皮肤纤维肉瘤隆突,版本1.2025,NCCN临床实践指南在肿瘤学。
IF 14.8 2区 医学
Journal of the National Comprehensive Cancer Network Pub Date : 2025-01-01 DOI: 10.6004/jnccn.2025.0001
Jeremy Bordeaux, Rachel Blitzblau, Sumaira Z Aasi, Murad Alam, Arya Amini, Kristin Bibee, Diana Bolotin, Pei-Ling Chen, Carlo M Contreras, Dominick DiMaio, Jessica M Donigan, Jeffrey M Farma, Karthik Ghosh, Kelly Harms, Nicole LeBoeuf, John Nicholas Lukens, Susan Manber, Lawrence Mark, Theresa Medina, Kishwer S Nehal, Paul Nghiem, Kelly Olino, Gyorgy Paragh, Soo Park, Tejesh Patel, Jason Rich, Ashok R Shaha, Bhavina Sharma, Yemi Sokumbi, Divya Srivastava, Valencia Thomas, Courtney Tomblinson, Puja Venkat, Yaohui Gloria Xu, Siegrid Yu, Mehran Yusuf, Beth McCullough, Sara Espinosa
{"title":"Dermatofibrosarcoma Protuberans, Version 1.2025, NCCN Clinical Practice Guidelines In Oncology.","authors":"Jeremy Bordeaux, Rachel Blitzblau, Sumaira Z Aasi, Murad Alam, Arya Amini, Kristin Bibee, Diana Bolotin, Pei-Ling Chen, Carlo M Contreras, Dominick DiMaio, Jessica M Donigan, Jeffrey M Farma, Karthik Ghosh, Kelly Harms, Nicole LeBoeuf, John Nicholas Lukens, Susan Manber, Lawrence Mark, Theresa Medina, Kishwer S Nehal, Paul Nghiem, Kelly Olino, Gyorgy Paragh, Soo Park, Tejesh Patel, Jason Rich, Ashok R Shaha, Bhavina Sharma, Yemi Sokumbi, Divya Srivastava, Valencia Thomas, Courtney Tomblinson, Puja Venkat, Yaohui Gloria Xu, Siegrid Yu, Mehran Yusuf, Beth McCullough, Sara Espinosa","doi":"10.6004/jnccn.2025.0001","DOIUrl":"https://doi.org/10.6004/jnccn.2025.0001","url":null,"abstract":"<p><p>Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous soft tissue sarcoma and affects an estimated 1,500 people annually in the United States. DFSP frequently exhibits extensive local infiltration. Initial treatment is through surgical excision, and care should be taken to ensure that negative margins are achieved to minimize recurrence. Although DFSP has a reported high rate of recurrence, metastasis is more uncommon. Fibrosarcomatous DFSP is an aggressive variant with an increased risk for local recurrence and metastasis. If achieving negative margins or resection is not feasible, radiation therapy or systemic treatment are options that may be considered by a multidisciplinary team. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) outline recommended treatment options available for DFSP.</p>","PeriodicalId":17483,"journal":{"name":"Journal of the National Comprehensive Cancer Network","volume":"23 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007759","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
Uncharted Territory: Investigating Long-Term Quality of Survival After A Prostate Cancer Diagnosis. 未知领域:调查前列腺癌诊断后的长期生存质量。
IF 14.8 2区 医学
Journal of the National Comprehensive Cancer Network Pub Date : 2025-01-01 DOI: 10.6004/jnccn.2024.7354
Alicia K Morgans, Charles J Ryan
{"title":"Uncharted Territory: Investigating Long-Term Quality of Survival After A Prostate Cancer Diagnosis.","authors":"Alicia K Morgans, Charles J Ryan","doi":"10.6004/jnccn.2024.7354","DOIUrl":"https://doi.org/10.6004/jnccn.2024.7354","url":null,"abstract":"","PeriodicalId":17483,"journal":{"name":"Journal of the National Comprehensive Cancer Network","volume":"23 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007761","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
Urinary Circular RNA Panels to Detect HBV-Related Hepatocellular Carcinoma: A Multicenter, Large-Scale, Case-Control Study. 尿环状RNA检测hbv相关肝细胞癌:一项多中心、大规模病例对照研究
IF 14.8 2区 医学
Journal of the National Comprehensive Cancer Network Pub Date : 2024-12-27 DOI: 10.6004/jnccn.2024.7058
Zijun Xie, Guangping Gan, Guanlin Zhou, Jiabao Zhang, Jiamin Ling, Jianhong Zhang, Yijun Zeng
{"title":"Urinary Circular RNA Panels to Detect HBV-Related Hepatocellular Carcinoma: A Multicenter, Large-Scale, Case-Control Study.","authors":"Zijun Xie, Guangping Gan, Guanlin Zhou, Jiabao Zhang, Jiamin Ling, Jianhong Zhang, Yijun Zeng","doi":"10.6004/jnccn.2024.7058","DOIUrl":"10.6004/jnccn.2024.7058","url":null,"abstract":"<p><strong>Purpose: </strong>More than 60% of patients with hepatocellular carcinoma (HCC) do not receive curative therapeutics due to late clinical manifestations and diagnosis. The 5-year survival rate for advanced HCC is approximately 2%. However, curative therapies for HCC detected early can improve the 5-year survival rate to >70%. We aimed to identify sensitive and noninvasive biomarkers in urine for detecting HCC.</p><p><strong>Patients and methods: </strong>For this study, 4 groups of individuals (healthy controls, patients with chronic hepatitis B [CHB], patients with hepatitis B virus [HBV]-induced liver cirrhosis, and patients with HBV-related HCC) were recruited, and each group was allocated to discovery, training, and validation phases. A total of 14 circular RNAs (circRNAs) were chosen as putative biomarkers in urine due to their differential expressions in HCC tissue and blood reported in related literature. Their expression levels in urine were measured by quantitative PCR (qPCR). Logistic regression models were created using a training cohort (n=312) and then validated using an independent cohort (n=741). Area under the receiver operating characteristic curve (AUC) was used to assess the diagnostic performances.</p><p><strong>Results: </strong>Three circRNA panels (circ_0075792, circ_0005397, and circ_0000976) were obtained with high diagnostic performances for differentiating HCC from the 3 control groups, with sensitivity >80%, specificity >90%, and AUC >0.9.</p><p><strong>Conclusions: </strong>Urinary circRNA panels identified and validated based on these results show desirable diagnostic performances for detecting HCC, especially early HCC. Accordingly, using these biomarkers to detect early HCC will enable patients who would have otherwise missed the curative therapeutic window to benefit from optimal treatments.</p>","PeriodicalId":17483,"journal":{"name":"Journal of the National Comprehensive Cancer Network","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895757","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
Response to EGFR/NTRK/MET Co-Inhibition Guided by Paired NGS in Advanced NSCLC With Acquired EGFR L858R/T790M/C797S Mutations. 在获得性EGFR L858R/T790M/C797S突变的晚期NSCLC中,配对NGS引导下EGFR/NTRK/MET共抑制的应答
IF 14.8 2区 医学
Journal of the National Comprehensive Cancer Network Pub Date : 2024-12-27 DOI: 10.6004/jnccn.2024.7070
Xue Yang, Xintong Li, Jiaqi Yan, Yuanxin Liu, Jie Yin, Weikang Shao, You Lu, Jianxin Xue
{"title":"Response to EGFR/NTRK/MET Co-Inhibition Guided by Paired NGS in Advanced NSCLC With Acquired EGFR L858R/T790M/C797S Mutations.","authors":"Xue Yang, Xintong Li, Jiaqi Yan, Yuanxin Liu, Jie Yin, Weikang Shao, You Lu, Jianxin Xue","doi":"10.6004/jnccn.2024.7070","DOIUrl":"https://doi.org/10.6004/jnccn.2024.7070","url":null,"abstract":"<p><p>EGFR tyrosine kinase inhibitors (TKIs) have significantly improved clinical outcomes for patients with non-small cell lung cancer (NSCLC) harboring EGFR-activating mutations. However, resistance to TKI therapy often develops due to secondary EGFR mutations or the activation of bypass signalling pathways. Next-generation sequencing (NGS) can efficiently identify actionable genetic alterations throughout treatment. MET amplification is a well-established off-target resistance mechanism. Additionally, rarer mechanisms, such as NTRK1 gene fusions, have been reported. This report highlights a case of a 58-year-old male diagnosed with bone-metastatic NSCLC harboring the EGFR L858R mutation. After receiving dacomitinib and almonertinib sequentially, plasma-based NGS revealed the emergence of EGFR T790M-trans-C797S mutations, prompting a switch to a combination therapy of almonertinib and gefitinib. Upon disease progression, repeat NGS identified EGFR T790M-cis&trans-C797S mutations and a novel POT1::NTRK3 fusion in the blood. The fusion retained a complete NTRK kinase domain without frameshift variants, making it a target for treatment. Larotrectinib was incorporated into the dual EGFR-TKI regimen, forming a triplet therapy. Although this resulted in grade 3 dermatitis, the condition resolved after discontinuing gefitinib. At multiorgan progression, matched tissue- and plasma-based NGS identified MET amplification. Subsequently, the patient was started on a triple-inhibition regimen targeting EGFR, NTRK, and MET, which achieved a partial response with favorable tolerability. This is the first reported case of a novel, targetable POT1::NTRK3 fusion as a potential off-target mechanism mediating EGFR-TKI resistance, occurring alongside MET amplification in a patient with NSCLC harboring acquired EGFR L858R/T790M/C797S mutations. Concomitant inhibition of EGFR, NTRK, and MET was safe and resulted in a significant response, underscoring the importance of precision medicine guided by matched NGS.</p>","PeriodicalId":17483,"journal":{"name":"Journal of the National Comprehensive Cancer Network","volume":" ","pages":"1-7"},"PeriodicalIF":14.8,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895754","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
Optimizing Ewing Sarcoma and Osteosarcoma Biopsy Acquisition: A Children's Oncology Group Bone Tumor Committee Consensus Statement. 优化尤文氏肉瘤和骨肉瘤活检获取:儿童肿瘤组骨肿瘤委员会共识声明。
IF 14.8 2区 医学
Journal of the National Comprehensive Cancer Network Pub Date : 2024-12-27 DOI: 10.6004/jnccn.2024.7063
Matthew S Dietz, Alyaa Al-Ibraheemi, Jessica L Davis, C Matthew Hawkins, Brian T Craig, Roshni Dasgupta, David S Geller, David S Shulman, Sarah Cohen-Gogo, Ajay Gupta, Susan L Whiteway, Emily K Slotkin, Christine M Heske, Safia K Ahmed, Daniel J Indelicato, Catherine M Albert, Nicole Montgomery, Jesse K Sandberg, Holcombe E Grier, Mark Krailo, Michael S Isakoff, Elyssa Rubin, Elizabeth R Lawlor, Steven G DuBois, Leo Mascarenhas, Patrick J Grohar, Odion Binitie, Damon Reed, Katherine Janeway, Ryan D Roberts, Kelly M Bailey
{"title":"Optimizing Ewing Sarcoma and Osteosarcoma Biopsy Acquisition: A Children's Oncology Group Bone Tumor Committee Consensus Statement.","authors":"Matthew S Dietz, Alyaa Al-Ibraheemi, Jessica L Davis, C Matthew Hawkins, Brian T Craig, Roshni Dasgupta, David S Geller, David S Shulman, Sarah Cohen-Gogo, Ajay Gupta, Susan L Whiteway, Emily K Slotkin, Christine M Heske, Safia K Ahmed, Daniel J Indelicato, Catherine M Albert, Nicole Montgomery, Jesse K Sandberg, Holcombe E Grier, Mark Krailo, Michael S Isakoff, Elyssa Rubin, Elizabeth R Lawlor, Steven G DuBois, Leo Mascarenhas, Patrick J Grohar, Odion Binitie, Damon Reed, Katherine Janeway, Ryan D Roberts, Kelly M Bailey","doi":"10.6004/jnccn.2024.7063","DOIUrl":"10.6004/jnccn.2024.7063","url":null,"abstract":"<p><p>Trends in diagnostic biopsy sample collection approaches for primary bone sarcomas have shifted in the past 2 decades. Although open/incisional biopsies used to be the predominant approach to obtain diagnostic material for Ewing sarcoma and osteosarcoma, image-guided core needle biopsies have increased in frequency and are safe for patients. These procedures are less invasive and reduce recovery times but have potential limitations. The quantity and quality of tissue obtained through these procedures vary between institutions. Acquired viable tissue volumes can be low, limiting the conduct of downstream expanded clinical workup, molecular analyses, and research. Patients with advanced Ewing sarcoma and osteosarcoma continue to have overall poor outcomes despite dose-intensive cytotoxic chemotherapy. The biology of treatment resistance is not currently well understood, partly due to limited availability of relevant tissue to study. There is a need for access to quality tumor specimens for molecular and other analyses to identify high-risk tumor subsets and drive discovery to improve patient outcomes. Given broad variability in bone tumor tissue procurement and processing across member institutions, the Children's Oncology Group Bone Tumor Committee convened a multidisciplinary group of experts to outline the current and near-future tissue needs for optimal clinical care and access to research platforms. The goal of this working group was to provide high-level guidance on biopsy practices that safely meet these evolving needs. Harmonizing tissue collection practices is paramount to improving the care of children, adolescents, and young adults diagnosed with Ewing sarcoma and osteosarcoma.</p>","PeriodicalId":17483,"journal":{"name":"Journal of the National Comprehensive Cancer Network","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895751","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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