{"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}
Purpose: 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.
Patients and methods: 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.
Results: 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.
Conclusions: 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.
{"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}
Xue Yang, Xintong Li, Jiaqi Yan, Yuanxin Liu, Jie Yin, Weikang Shao, You Lu, Jianxin Xue
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.
{"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":"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":""},"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}
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
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.
{"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}
Longbin Xiong, Xingli Shan, Huali Ma, Shengjie Guo, Jiyan Liu, Xianda Chen, Wenjun Meng, Bin Guo, Lijuan Jiang, Ru Yan, Xin An, Yanxia Shi, Yijun Zhang, Ting Xue, Lichao Wei, Daming Xu, Zhiling Zhang, Zike Qin, Kai Yao, Yajian Li, Philippe E Spiess, Linjun Hu, Nianzeng Xing, Hui Han
Background: The purpose of this study was to evaluate the efficacy and safety of PD-1 blockade combined with cisplatin and paclitaxel (TP)-based chemotherapy as first-line treatment for advanced penile squamous cell carcinoma (PSCC).
Patients and methods: A retrospective review was performed of 32 eligible patients with high-risk stage IV (cN3M0-1) PSCC who received first-line PD-1 blockade combined with TP-based chemotherapy at 5 medical centers (2019-2023). Clinical responses were assessed using RECIST version 1.1. Treatment-related adverse events (TrAEs) and postsurgical complications were graded according to CTCAE version 5.0. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Multiplex immunofluorescence was used to explore potential biomarkers and to present the tumor microenvironment landscape before and after treatment.
Results: After a median treatment duration of 4 cycles (range, 2-6), the overall objective response rate was 78.1% (25/32). Among 27 patients with locally advanced PSCC, 13 (48.1%) subsequently underwent consolidative surgery and 6 (22.2%) achieved a pathologic complete response (pCR). Additionally, 8 (25.0%) patients in the overall cohort underwent consolidated radiotherapy. Median follow-up was 21.1 months (95% CI, 14.1-42.7). Median PFS and OS were 15.0 months (95% CI, 11.4-not available [NA]) and 19.3 months (95% CI, 16.7-NA), respectively. All patients experienced TrAEs, with 50% (16/32) of them having grade ≥3 TrAEs. Higher intratumoral CD8+ T-cell infiltration was observed in pretreatment samples of responders compared with nonresponders (P=.03). CD4+ T-cells, natural killer cells, and macrophages, among others, exhibited significant changes after treatment (all P<.05), suggesting their potential involvement in the antitumor response to immunochemotherapy.
Conclusions: PD-1 blockade plus TP-based chemotherapy was effective and well tolerated, with favorable survival outcomes for patients with stage IV PSCC. High pretreatment intratumoral CD8+ T-cell infiltration may help to identify potential responders.
{"title":"First-Line PD-1 Blockade Combined With Chemotherapy for Stage IV Penile Squamous Cell Carcinoma: A Multicenter Retrospective Study.","authors":"Longbin Xiong, Xingli Shan, Huali Ma, Shengjie Guo, Jiyan Liu, Xianda Chen, Wenjun Meng, Bin Guo, Lijuan Jiang, Ru Yan, Xin An, Yanxia Shi, Yijun Zhang, Ting Xue, Lichao Wei, Daming Xu, Zhiling Zhang, Zike Qin, Kai Yao, Yajian Li, Philippe E Spiess, Linjun Hu, Nianzeng Xing, Hui Han","doi":"10.6004/jnccn.2024.7074","DOIUrl":"10.6004/jnccn.2024.7074","url":null,"abstract":"<p><strong>Background: </strong>The purpose of this study was to evaluate the efficacy and safety of PD-1 blockade combined with cisplatin and paclitaxel (TP)-based chemotherapy as first-line treatment for advanced penile squamous cell carcinoma (PSCC).</p><p><strong>Patients and methods: </strong>A retrospective review was performed of 32 eligible patients with high-risk stage IV (cN3M0-1) PSCC who received first-line PD-1 blockade combined with TP-based chemotherapy at 5 medical centers (2019-2023). Clinical responses were assessed using RECIST version 1.1. Treatment-related adverse events (TrAEs) and postsurgical complications were graded according to CTCAE version 5.0. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Multiplex immunofluorescence was used to explore potential biomarkers and to present the tumor microenvironment landscape before and after treatment.</p><p><strong>Results: </strong>After a median treatment duration of 4 cycles (range, 2-6), the overall objective response rate was 78.1% (25/32). Among 27 patients with locally advanced PSCC, 13 (48.1%) subsequently underwent consolidative surgery and 6 (22.2%) achieved a pathologic complete response (pCR). Additionally, 8 (25.0%) patients in the overall cohort underwent consolidated radiotherapy. Median follow-up was 21.1 months (95% CI, 14.1-42.7). Median PFS and OS were 15.0 months (95% CI, 11.4-not available [NA]) and 19.3 months (95% CI, 16.7-NA), respectively. All patients experienced TrAEs, with 50% (16/32) of them having grade ≥3 TrAEs. Higher intratumoral CD8+ T-cell infiltration was observed in pretreatment samples of responders compared with nonresponders (P=.03). CD4+ T-cells, natural killer cells, and macrophages, among others, exhibited significant changes after treatment (all P<.05), suggesting their potential involvement in the antitumor response to immunochemotherapy.</p><p><strong>Conclusions: </strong>PD-1 blockade plus TP-based chemotherapy was effective and well tolerated, with favorable survival outcomes for patients with stage IV PSCC. High pretreatment intratumoral CD8+ T-cell infiltration may help to identify potential responders.</p>","PeriodicalId":17483,"journal":{"name":"Journal of the National Comprehensive Cancer Network","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872431","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}
Daniel Sentana-Lledo, Anurag Saraf, Alicia K Morgans
Prostate cancer survivors represent a growing population of patients with a diagnosis of prostate cancer, whether they were cured using local therapies or continue to receive systemic treatment of advanced disease. Many patients receive androgen deprivation therapy (ADT) during treatment, which is associated with many long-lasting physical and psychological effects. Identifying and addressing the needs of survivors is imperative for improving their health and well-being. This narrative review highlights the most common issues associated with ADT affecting survivorship in prostate cancer, including cardiovascular and metabolic effects, musculoskeletal health, sexual morbidity, and local therapy effects, as well as the mental and psychological toll. A special emphasis is placed on the existing literature examining specific interventions to alleviate these symptoms, along with describing existing gaps in knowledge, with the goal of promoting dedicated studies aimed at enhancing the survivorship experience of patients with prostate cancer.
{"title":"Symptom Burden and Survivorship Care for Patients With Prostate Cancer on Androgen Deprivation Therapy.","authors":"Daniel Sentana-Lledo, Anurag Saraf, Alicia K Morgans","doi":"10.6004/jnccn.2024.7047","DOIUrl":"10.6004/jnccn.2024.7047","url":null,"abstract":"<p><p>Prostate cancer survivors represent a growing population of patients with a diagnosis of prostate cancer, whether they were cured using local therapies or continue to receive systemic treatment of advanced disease. Many patients receive androgen deprivation therapy (ADT) during treatment, which is associated with many long-lasting physical and psychological effects. Identifying and addressing the needs of survivors is imperative for improving their health and well-being. This narrative review highlights the most common issues associated with ADT affecting survivorship in prostate cancer, including cardiovascular and metabolic effects, musculoskeletal health, sexual morbidity, and local therapy effects, as well as the mental and psychological toll. A special emphasis is placed on the existing literature examining specific interventions to alleviate these symptoms, along with describing existing gaps in knowledge, with the goal of promoting dedicated studies aimed at enhancing the survivorship experience of patients with prostate cancer.</p>","PeriodicalId":17483,"journal":{"name":"Journal of the National Comprehensive Cancer Network","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872433","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}
Taymeyah Al-Toubah, Mintallah Haider, Eleonora Pelle, Maria Grazia Maratta, Jonathan Strosberg
Background: Neuroendocrine tumors (NETs) of the appendix are typically detected incidentally during appendectomy. Recent studies reported no metachronous metastases among patients with primary tumors <2 cm, regardless of lymph node status or referral for completion hemicolectomy. However, questions persist regarding the possibility of metastases developing decades after surgical resection, particularly because appendiceal NETs are frequently diagnosed in young adults and children. Therefore, we sought to evaluate patients with metastatic appendiceal NETs to assess whether any had been diagnosed previously with an early-stage appendiceal NET.
Methods: We analyzed a large institutional neuroendocrine tumor database to identify appendiceal NETs of all stages and ascertain whether any patients with localized tumors developed metastases and whether any with metastatic disease had initially presented with an early-stage tumor.
Results: Of 3,795 patients with gastroenteropancreatic (GEP) NETs seen in an oncologic NET clinic between January 2008 and August 2023, 124 presented with appendiceal NETs. Of these, only 10 (<0.3% of the total GEP-NET population) had stage IV disease, 8 of whom were diagnosed synchronously at the time of initial diagnosis. Two patients with metastatic disease had reportedly undergone surgical resection for a primary appendiceal NET approximately 20 years before the diagnosis of metastatic disease, but medical records were not available to confirm an appendiceal primary.
Conclusions: Stage IV appendiceal NETs are exceptionally rare, and distant metastases are synchronous in nearly all cases. The risk of metastatic spread after resection of local appendiceal NETs is negligible. Patients with tumors <2 cm should not be managed with completion right hemicolectomy, and the role of this operation for larger tumors is questionable. Postoperative surveillance is unlikely to be of benefit.
{"title":"Do Appendiceal Neuroendocrine Tumors Metastasize Post Appendectomy or Right Hemicolectomy?","authors":"Taymeyah Al-Toubah, Mintallah Haider, Eleonora Pelle, Maria Grazia Maratta, Jonathan Strosberg","doi":"10.6004/jnccn.2024.7069","DOIUrl":"10.6004/jnccn.2024.7069","url":null,"abstract":"<p><strong>Background: </strong>Neuroendocrine tumors (NETs) of the appendix are typically detected incidentally during appendectomy. Recent studies reported no metachronous metastases among patients with primary tumors <2 cm, regardless of lymph node status or referral for completion hemicolectomy. However, questions persist regarding the possibility of metastases developing decades after surgical resection, particularly because appendiceal NETs are frequently diagnosed in young adults and children. Therefore, we sought to evaluate patients with metastatic appendiceal NETs to assess whether any had been diagnosed previously with an early-stage appendiceal NET.</p><p><strong>Methods: </strong>We analyzed a large institutional neuroendocrine tumor database to identify appendiceal NETs of all stages and ascertain whether any patients with localized tumors developed metastases and whether any with metastatic disease had initially presented with an early-stage tumor.</p><p><strong>Results: </strong>Of 3,795 patients with gastroenteropancreatic (GEP) NETs seen in an oncologic NET clinic between January 2008 and August 2023, 124 presented with appendiceal NETs. Of these, only 10 (<0.3% of the total GEP-NET population) had stage IV disease, 8 of whom were diagnosed synchronously at the time of initial diagnosis. Two patients with metastatic disease had reportedly undergone surgical resection for a primary appendiceal NET approximately 20 years before the diagnosis of metastatic disease, but medical records were not available to confirm an appendiceal primary.</p><p><strong>Conclusions: </strong>Stage IV appendiceal NETs are exceptionally rare, and distant metastases are synchronous in nearly all cases. The risk of metastatic spread after resection of local appendiceal NETs is negligible. Patients with tumors <2 cm should not be managed with completion right hemicolectomy, and the role of this operation for larger tumors is questionable. Postoperative surveillance is unlikely to be of benefit.</p>","PeriodicalId":17483,"journal":{"name":"Journal of the National Comprehensive Cancer Network","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872428","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}
Stephanie O Dudzinski, Maria E Cabanillas, Sarah Hamidi, Vicente R Marczyk, Naifa L Busaidy, Ramona Dadu, James Welsh, Mimi I Hu, G Brandon Gunn, Chenyang Wang, Steven G Waguespack, Jack Phan, Thomas H Beckham, Joe Y Chang, Steven I Sherman, Jay P Reddy, Anita K Ying, Michael S O'Reilly, Aileen Chen, Anna Lee, Saumil J Gandhi, Zhongxing Liao, Ethan B Ludmir, Quynh-Nhu Nguyen, Steven H Lin, Mark E Zafereo, Matthew S Ning
Background: Definitive radiotherapy (dRT) has been shown to be an effective option for patients with oligometastatic and oligoprogressive cancers; however, this approach has not been well-studied in metastatic thyroid cancer.
Methods: This retrospective cohort included 119 patients with oligometastatic (34%) and oligoprogressive (66%) metastatic thyroid cancer treated from 2005 to 2024 with 207 dRT courses for 344 sites (50% thoracic, 37% bone, 7.5% brain, 4% abdominopelvic, and 1.5% neck/skull base). Histologies included 61% papillary, 15% poorly differentiated, 13% follicular, and 10% oncocytic, and 114 (96%) patients had radioiodine-refractory disease prior to dRT. Each course involved 1 to 5 sites, with prescriptions intended for definitive control (median BED10, 72 Gy), and palliative RT was excluded. Somatic mutation testing for oncologic drivers was performed in 103 (87%) patients.
Results: Each patient had an average of 3 sites (range, 1-23) treated over 2 courses (range, 1-9). Follow-up from first dRT was a median 2.5 years, with overall survival at 3 and 5 years of 81.5% and 70%, respectively. Actuarial local control per site was 91% at 3 years. Median progression-free survival (PFS) after first course was 17 months (95% CI, 10-24 months), with poorly differentiated histology associated with worse outcomes (hazard ratio [HR], 2.20; 95% CI, 1.24-3.90; P=.007), BRAF mutation with improved PFS (HR, 0.59; 95% CI, 0.37-0.95; P=.029), and no significant findings with respect to systemic therapy. At initial dRT, 92 (77%) patients were not on systemic therapy; and after first dRT, freedom from systemic therapy escalation was a median 4.1 years (95% CI, 1.7-6.5 years), with 2- and 5-year continued deferral rates of 73% and 46%, respectively. Grade 3 toxicities were noted for 1.5% of courses, with no grade 4-5 events observed.
Conclusions: This study underscores the potential of dRT as a feasible strategy for deferring systemic therapy escalation in patients with oligometastatic and oligoprogressive metastatic thyroid cancer, demonstrating that sequential dRT courses impart excellent local control and are safe to deliver repeatedly for multiple distant sites. Further studies are warranted to validate these findings and elucidate the full benefit of dRT as part of a multidisciplinary approach for metastatic thyroid cancer.
{"title":"Definitive Radiotherapy for Oligometastatic and Oligoprogressive Thyroid Cancer: A Potential Strategy for Systemic Therapy Deferral.","authors":"Stephanie O Dudzinski, Maria E Cabanillas, Sarah Hamidi, Vicente R Marczyk, Naifa L Busaidy, Ramona Dadu, James Welsh, Mimi I Hu, G Brandon Gunn, Chenyang Wang, Steven G Waguespack, Jack Phan, Thomas H Beckham, Joe Y Chang, Steven I Sherman, Jay P Reddy, Anita K Ying, Michael S O'Reilly, Aileen Chen, Anna Lee, Saumil J Gandhi, Zhongxing Liao, Ethan B Ludmir, Quynh-Nhu Nguyen, Steven H Lin, Mark E Zafereo, Matthew S Ning","doi":"10.6004/jnccn.2024.7072","DOIUrl":"10.6004/jnccn.2024.7072","url":null,"abstract":"<p><strong>Background: </strong>Definitive radiotherapy (dRT) has been shown to be an effective option for patients with oligometastatic and oligoprogressive cancers; however, this approach has not been well-studied in metastatic thyroid cancer.</p><p><strong>Methods: </strong>This retrospective cohort included 119 patients with oligometastatic (34%) and oligoprogressive (66%) metastatic thyroid cancer treated from 2005 to 2024 with 207 dRT courses for 344 sites (50% thoracic, 37% bone, 7.5% brain, 4% abdominopelvic, and 1.5% neck/skull base). Histologies included 61% papillary, 15% poorly differentiated, 13% follicular, and 10% oncocytic, and 114 (96%) patients had radioiodine-refractory disease prior to dRT. Each course involved 1 to 5 sites, with prescriptions intended for definitive control (median BED10, 72 Gy), and palliative RT was excluded. Somatic mutation testing for oncologic drivers was performed in 103 (87%) patients.</p><p><strong>Results: </strong>Each patient had an average of 3 sites (range, 1-23) treated over 2 courses (range, 1-9). Follow-up from first dRT was a median 2.5 years, with overall survival at 3 and 5 years of 81.5% and 70%, respectively. Actuarial local control per site was 91% at 3 years. Median progression-free survival (PFS) after first course was 17 months (95% CI, 10-24 months), with poorly differentiated histology associated with worse outcomes (hazard ratio [HR], 2.20; 95% CI, 1.24-3.90; P=.007), BRAF mutation with improved PFS (HR, 0.59; 95% CI, 0.37-0.95; P=.029), and no significant findings with respect to systemic therapy. At initial dRT, 92 (77%) patients were not on systemic therapy; and after first dRT, freedom from systemic therapy escalation was a median 4.1 years (95% CI, 1.7-6.5 years), with 2- and 5-year continued deferral rates of 73% and 46%, respectively. Grade 3 toxicities were noted for 1.5% of courses, with no grade 4-5 events observed.</p><p><strong>Conclusions: </strong>This study underscores the potential of dRT as a feasible strategy for deferring systemic therapy escalation in patients with oligometastatic and oligoprogressive metastatic thyroid cancer, demonstrating that sequential dRT courses impart excellent local control and are safe to deliver repeatedly for multiple distant sites. Further studies are warranted to validate these findings and elucidate the full benefit of dRT as part of a multidisciplinary approach for metastatic thyroid cancer.</p>","PeriodicalId":17483,"journal":{"name":"Journal of the National Comprehensive Cancer Network","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813660","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}
Valentin H Meissner, Kolja Imhof, Matthias Jahnen, Lukas Lunger, Andreas Dinkel, Stefan Schiele, Donna P Ankerst, Jürgen E Gschwend, Kathleen Herkommer
Background: Frailty is emerging as an important determinant for quality of life (QoL) and emotional health in older patients with cancer, and specifically in long-term prostate cancer survivors, but quantitative studies are lacking. The current study assesses the prevalence of frailty and its association with QoL and emotional health in long-term prostate cancer survivors after radical prostatectomy.
Patients and methods: A total of 2,979 prostate cancer survivors from the multicenter German Familial Prostate Cancer cohort completed questionnaires on frailty (Groningen Frailty Indicator [GFI]), QoL (EORTC QoL Questionnaire-Core 30), and emotional health (anxiety/depression symptoms via the Patient Health Questionnaire-4). Modified Poisson regression analysis was used to assess factors associated with frailty.
Results: Average patient age was 79.4 years [SD, 6.4 years] and average time since radical prostatectomy was 17.4 years [SD, 3.8 years]. Among the cohort, 33.1% (n=985) of patients were classified as frail (GFI ≥4). Frail patients reported worse emotional health than nonfrail patients (depression symptoms: 24.0% vs 4.0%; anxiety symptoms: 20.6% vs 2.0%; both P<.001) and lower QoL (mean [SD], 53.4 [19.2] vs 72.7 [16.0]); P<.001). Higher age (relative risk [RR], 1.02; 95% CI, 1.01-1.03) and worse depressive (RR, 1.18; 95% CI, 1.12-1.24) and anxiety symptoms (RR, 1.17; 95% CI, 1.11-1.23) were associated with frailty. Living in a partnership (RR, 0.76; 95% CI, 0.67-0.86) and a higher QoL (RR, 0.86 for a 10-point increase; 95% CI, 0.84-0.89) were associated with nonfrailty.
Conclusions: In a large German cohort, every third long-term prostate cancer survivor after radical prostatectomy was frail. The association of frailty with lower QoL and poorer mental health indicates the need for an integrated care approach including further geriatric assessment and possible interventions to improve health outcomes targeted to frail patients.
背景:衰弱正在成为老年癌症患者,特别是长期前列腺癌幸存者生活质量(QoL)和情绪健康的重要决定因素,但缺乏定量研究。本研究评估了根治性前列腺切除术后长期前列腺癌幸存者的虚弱患病率及其与生活质量和情绪健康的关系。患者和方法:来自多中心德国家族性前列腺癌队列的2979名前列腺癌幸存者完成了衰弱(格罗宁根衰弱指标[GFI])、生活质量(EORTC生活质量问卷- core 30)和情绪健康(患者健康问卷-4的焦虑/抑郁症状)的问卷调查。采用修正泊松回归分析评估与虚弱相关的因素。结果:患者平均年龄79.4岁[SD, 6.4岁],根治性前列腺切除术后平均时间17.4年[SD, 3.8年]。在队列中,33.1% (n=985)的患者被分类为虚弱(GFI≥4)。体弱多病患者报告的情绪健康状况比非体弱多病患者差(抑郁症状:24.0% vs 4.0%;焦虑症状:20.6% vs 2.0%;结论:在一项大型德国队列研究中,根治性前列腺切除术后三分之一的长期前列腺癌幸存者身体虚弱。虚弱与较低的生活质量和较差的精神健康之间的关联表明,需要采取综合护理方法,包括进一步的老年评估和可能的干预措施,以改善针对虚弱患者的健康结果。
{"title":"Frailty in Long-Term Prostate Cancer Survivors and Its Association With Quality of Life and Emotional Health.","authors":"Valentin H Meissner, Kolja Imhof, Matthias Jahnen, Lukas Lunger, Andreas Dinkel, Stefan Schiele, Donna P Ankerst, Jürgen E Gschwend, Kathleen Herkommer","doi":"10.6004/jnccn.2024.7066","DOIUrl":"10.6004/jnccn.2024.7066","url":null,"abstract":"<p><strong>Background: </strong>Frailty is emerging as an important determinant for quality of life (QoL) and emotional health in older patients with cancer, and specifically in long-term prostate cancer survivors, but quantitative studies are lacking. The current study assesses the prevalence of frailty and its association with QoL and emotional health in long-term prostate cancer survivors after radical prostatectomy.</p><p><strong>Patients and methods: </strong>A total of 2,979 prostate cancer survivors from the multicenter German Familial Prostate Cancer cohort completed questionnaires on frailty (Groningen Frailty Indicator [GFI]), QoL (EORTC QoL Questionnaire-Core 30), and emotional health (anxiety/depression symptoms via the Patient Health Questionnaire-4). Modified Poisson regression analysis was used to assess factors associated with frailty.</p><p><strong>Results: </strong>Average patient age was 79.4 years [SD, 6.4 years] and average time since radical prostatectomy was 17.4 years [SD, 3.8 years]. Among the cohort, 33.1% (n=985) of patients were classified as frail (GFI ≥4). Frail patients reported worse emotional health than nonfrail patients (depression symptoms: 24.0% vs 4.0%; anxiety symptoms: 20.6% vs 2.0%; both P<.001) and lower QoL (mean [SD], 53.4 [19.2] vs 72.7 [16.0]); P<.001). Higher age (relative risk [RR], 1.02; 95% CI, 1.01-1.03) and worse depressive (RR, 1.18; 95% CI, 1.12-1.24) and anxiety symptoms (RR, 1.17; 95% CI, 1.11-1.23) were associated with frailty. Living in a partnership (RR, 0.76; 95% CI, 0.67-0.86) and a higher QoL (RR, 0.86 for a 10-point increase; 95% CI, 0.84-0.89) were associated with nonfrailty.</p><p><strong>Conclusions: </strong>In a large German cohort, every third long-term prostate cancer survivor after radical prostatectomy was frail. The association of frailty with lower QoL and poorer mental health indicates the need for an integrated care approach including further geriatric assessment and possible interventions to improve health outcomes targeted to frail patients.</p>","PeriodicalId":17483,"journal":{"name":"Journal of the National Comprehensive Cancer Network","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813662","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}
{"title":"The Oncologist Outside the Exam Room.","authors":"Daniel M Geynisman","doi":"10.6004/jnccn.2024.0063","DOIUrl":"10.6004/jnccn.2024.0063","url":null,"abstract":"","PeriodicalId":17483,"journal":{"name":"Journal of the National Comprehensive Cancer Network","volume":"22 10","pages":"645-646"},"PeriodicalIF":14.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846799","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}