Pub Date : 2024-08-21eCollection Date: 2024-01-01DOI: 10.1177/17588359241266164
Astrid Kramer, Marjolein J E Greuter, Suzanna J Schraa, Geraldine R Vink, Jillian Phallen, Victor E Velculescu, Gerrit A Meijer, Daan van den Broek, Miriam Koopman, Jeanine M L Roodhart, Remond J A Fijneman, Valesca P Retèl, Veerle M H Coupé
Background: Current patient selection for adjuvant chemotherapy (ACT) after curative surgery for stage II colon cancer (CC) is suboptimal, causing overtreatment of high-risk patients and undertreatment of low-risk patients. Postoperative circulating tumor DNA (ctDNA) could improve patient selection for ACT.
Objectives: We conducted an early model-based evaluation of the (cost-)effectiveness of ctDNA-guided selection for ACT in stage II CC in the Netherlands to assess the conditions for cost-effective implementation.
Methods: A validated Markov model, simulating 1000 stage II CC patients from diagnosis to death, was supplemented with ctDNA data. Five ACT selection strategies were evaluated: the current guideline (pT4, pMMR), ctDNA-only, and three strategies that combined ctDNA status with pT4 and pMMR status in different ways. For each strategy, the costs, life years, quality-adjusted life years (QALYs), recurrences, and CC deaths were estimated. Sensitivity analyses were performed to assess the impact of the costs of ctDNA testing, strategy adherence, ctDNA as a predictive biomarker, and ctDNA test performance.
Results: Model predictions showed that compared to current guidelines, the ctDNA-only strategy was less effective (+2.2% recurrences, -0.016 QALYs), while the combination strategies were more effective (-3.6% recurrences, +0.038 QALYs). The combination strategies were not cost-effective, since the incremental cost-effectiveness ratio was €67,413 per QALY, exceeding the willingness-to-pay threshold of €50,000 per QALY. Sensitivity analyses showed that the combination strategies would be cost-effective if the ctDNA test costs were lower than €1500, or if ctDNA status was predictive of treatment response, or if the ctDNA test performance improved substantially.
Conclusion: Adding ctDNA to current high-risk clinicopathological features (pT4 and pMMR) can improve patient selection for ACT and can also potentially be cost-effective. Future studies should investigate the predictive value of post-surgery ctDNA status to accurately evaluate the cost-effectiveness of ctDNA testing for ACT decisions in stage II CC.
{"title":"Early evaluation of the effectiveness and cost-effectiveness of ctDNA-guided selection for adjuvant chemotherapy in stage II colon cancer.","authors":"Astrid Kramer, Marjolein J E Greuter, Suzanna J Schraa, Geraldine R Vink, Jillian Phallen, Victor E Velculescu, Gerrit A Meijer, Daan van den Broek, Miriam Koopman, Jeanine M L Roodhart, Remond J A Fijneman, Valesca P Retèl, Veerle M H Coupé","doi":"10.1177/17588359241266164","DOIUrl":"10.1177/17588359241266164","url":null,"abstract":"<p><strong>Background: </strong>Current patient selection for adjuvant chemotherapy (ACT) after curative surgery for stage II colon cancer (CC) is suboptimal, causing overtreatment of high-risk patients and undertreatment of low-risk patients. Postoperative circulating tumor DNA (ctDNA) could improve patient selection for ACT.</p><p><strong>Objectives: </strong>We conducted an early model-based evaluation of the (cost-)effectiveness of ctDNA-guided selection for ACT in stage II CC in the Netherlands to assess the conditions for cost-effective implementation.</p><p><strong>Methods: </strong>A validated Markov model, simulating 1000 stage II CC patients from diagnosis to death, was supplemented with ctDNA data. Five ACT selection strategies were evaluated: the current guideline (pT4, pMMR), ctDNA-only, and three strategies that combined ctDNA status with pT4 and pMMR status in different ways. For each strategy, the costs, life years, quality-adjusted life years (QALYs), recurrences, and CC deaths were estimated. Sensitivity analyses were performed to assess the impact of the costs of ctDNA testing, strategy adherence, ctDNA as a predictive biomarker, and ctDNA test performance.</p><p><strong>Results: </strong>Model predictions showed that compared to current guidelines, the ctDNA-only strategy was less effective (+2.2% recurrences, -0.016 QALYs), while the combination strategies were more effective (-3.6% recurrences, +0.038 QALYs). The combination strategies were not cost-effective, since the incremental cost-effectiveness ratio was €67,413 per QALY, exceeding the willingness-to-pay threshold of €50,000 per QALY. Sensitivity analyses showed that the combination strategies would be cost-effective if the ctDNA test costs were lower than €1500, or if ctDNA status was predictive of treatment response, or if the ctDNA test performance improved substantially.</p><p><strong>Conclusion: </strong>Adding ctDNA to current high-risk clinicopathological features (pT4 and pMMR) can improve patient selection for ACT and can also potentially be cost-effective. Future studies should investigate the predictive value of post-surgery ctDNA status to accurately evaluate the cost-effectiveness of ctDNA testing for ACT decisions in stage II CC.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241266164"},"PeriodicalIF":4.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037063","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 : 2024-08-15eCollection Date: 2024-01-01DOI: 10.1177/17588359241266140
Julia Zarychta, Adrian Kowalczyk, Anna Marszołek, Joanna Zawitkowska, Monika Lejman
Despite significant progress in the treatment of some types of cancer, high-grade gliomas (HGGs) remain a significant clinical problem. In the case of glioblastoma (GBM), the most common solid tumor of the central nervous system in adults, the average survival time from diagnosis is only 15-18 months, despite the use of intensive multimodal therapy. Chimeric antigen receptor (CAR)-expressing T cells, which have already been approved by the Food and Drug Administration for use in the treatment of certain hematologic malignancies, are a new, promising therapeutic option. However, the efficacy of CAR-T cells in solid tumors is lower due to the immunosuppressive tumor microenvironment (TME). Reprogramming the immunosuppressive TME toward a pro-inflammatory phenotype therefore seems particularly important because it may allow for increasing the effectiveness of CAR-T cells in the therapy of solid tumors. The following literature review aims to present the results of preclinical studies showing the possibilities of improving the efficacy of CAR-T in the TME of GBM by reprogramming the TME toward a pro-inflammatory phenotype. It may be achievable thanks to the use of CAR-T in a synergistic therapy in combination with oncolytic viruses, radiotherapy, or epigenetic inhibitors, as well as by supporting CAR-T cells crossing of the blood-brain barrier, normalizing impaired angiogenesis in the TME, improving CAR-T effector functions by cytokine signaling or by blocking/knocking out T-cell inhibitors, and modulating the microRNA expression. The use of CAR-T cells modified in this way in synergistic therapy could lead to the longer survival of patients with HGG by inducing an endogenous anti-tumor response.
{"title":"Strategies to overcome tumor microenvironment immunosuppressive effect on the functioning of CAR-T cells in high-grade glioma.","authors":"Julia Zarychta, Adrian Kowalczyk, Anna Marszołek, Joanna Zawitkowska, Monika Lejman","doi":"10.1177/17588359241266140","DOIUrl":"10.1177/17588359241266140","url":null,"abstract":"<p><p>Despite significant progress in the treatment of some types of cancer, high-grade gliomas (HGGs) remain a significant clinical problem. In the case of glioblastoma (GBM), the most common solid tumor of the central nervous system in adults, the average survival time from diagnosis is only 15-18 months, despite the use of intensive multimodal therapy. Chimeric antigen receptor (CAR)-expressing T cells, which have already been approved by the Food and Drug Administration for use in the treatment of certain hematologic malignancies, are a new, promising therapeutic option. However, the efficacy of CAR-T cells in solid tumors is lower due to the immunosuppressive tumor microenvironment (TME). Reprogramming the immunosuppressive TME toward a pro-inflammatory phenotype therefore seems particularly important because it may allow for increasing the effectiveness of CAR-T cells in the therapy of solid tumors. The following literature review aims to present the results of preclinical studies showing the possibilities of improving the efficacy of CAR-T in the TME of GBM by reprogramming the TME toward a pro-inflammatory phenotype. It may be achievable thanks to the use of CAR-T in a synergistic therapy in combination with oncolytic viruses, radiotherapy, or epigenetic inhibitors, as well as by supporting CAR-T cells crossing of the blood-brain barrier, normalizing impaired angiogenesis in the TME, improving CAR-T effector functions by cytokine signaling or by blocking/knocking out T-cell inhibitors, and modulating the microRNA expression. The use of CAR-T cells modified in this way in synergistic therapy could lead to the longer survival of patients with HGG by inducing an endogenous anti-tumor response.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241266140"},"PeriodicalIF":4.3,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11327996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000720","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 : 2024-08-10eCollection Date: 2024-01-01DOI: 10.1177/17588359241259466
Francesca Sofia Di Lisa, Alice Villa, Lorena Filomeno, Teresa Arcuri, Benito Chiofalo, Giuseppe Sanguineti, Laura Pizzuti, Eriseld Krasniqi, Maddalena Barba, Domenico Sergi, Francesco Lombardo, Francesco Romanelli, Claudio Botti, Giovanni Zoccali, Gennaro Ciliberto, Patrizia Vici
Transgender individuals exhibit a higher prevalence of cancer-related risk factors, such as substance abuse and sexually transmitted infections. These factors, coupled with suboptimal adherence to cancer screening recommendations, may lead to a higher incidence of cancers, such as breast and cervical cancer, and contribute to delayed diagnoses in transgender patients. Herein, we report a unique case of a transgender man with a history of alcohol and drug abuse, undergoing gender-affirming exogenous testosterone therapy, who developed synchronous locally advanced breast cancer and human papilloma virus (HPV)-related cervical cancer. He underwent concurrent chemoradiation for cervical cancer and surgery followed by endocrine therapy for breast cancer. The treatments were suboptimals due to patient's comorbidities, among them liver cirrhosis leading to an early death. Additionally, we have conducted a review of existing literature, including case reports, clinical studies, and review articles investigating the role of potential risk factors specifically related to breast and cervical tumors in transgender men. Gender-affirming testosterone therapy is common among transgender men to induce gender affirmation, but its link to breast cancer risk remains ambiguous, with studies being limited and sometimes contradictory. Conversely, HPV is a well-established cause of up to 99% of cervical cancers. Despite persistent risk for cervical cancer in transgender men who retain their cervix, several studies indicate notable disparities in screening adherence, due to personal and structural barriers. Moreover, alcohol and drug use disorders, commonly encountered in transgender population, may negatively influence the adherence to screening programs. Current cancer screening guidelines for this population are somewhat unclear, and specific programs based on more robust data are urgently required along with further tailored studies.
{"title":"Breast and cervical cancer in transgender men: literature review and a case report.","authors":"Francesca Sofia Di Lisa, Alice Villa, Lorena Filomeno, Teresa Arcuri, Benito Chiofalo, Giuseppe Sanguineti, Laura Pizzuti, Eriseld Krasniqi, Maddalena Barba, Domenico Sergi, Francesco Lombardo, Francesco Romanelli, Claudio Botti, Giovanni Zoccali, Gennaro Ciliberto, Patrizia Vici","doi":"10.1177/17588359241259466","DOIUrl":"10.1177/17588359241259466","url":null,"abstract":"<p><p>Transgender individuals exhibit a higher prevalence of cancer-related risk factors, such as substance abuse and sexually transmitted infections. These factors, coupled with suboptimal adherence to cancer screening recommendations, may lead to a higher incidence of cancers, such as breast and cervical cancer, and contribute to delayed diagnoses in transgender patients. Herein, we report a unique case of a transgender man with a history of alcohol and drug abuse, undergoing gender-affirming exogenous testosterone therapy, who developed synchronous locally advanced breast cancer and human papilloma virus (HPV)-related cervical cancer. He underwent concurrent chemoradiation for cervical cancer and surgery followed by endocrine therapy for breast cancer. The treatments were suboptimals due to patient's comorbidities, among them liver cirrhosis leading to an early death. Additionally, we have conducted a review of existing literature, including case reports, clinical studies, and review articles investigating the role of potential risk factors specifically related to breast and cervical tumors in transgender men. Gender-affirming testosterone therapy is common among transgender men to induce gender affirmation, but its link to breast cancer risk remains ambiguous, with studies being limited and sometimes contradictory. Conversely, HPV is a well-established cause of up to 99% of cervical cancers. Despite persistent risk for cervical cancer in transgender men who retain their cervix, several studies indicate notable disparities in screening adherence, due to personal and structural barriers. Moreover, alcohol and drug use disorders, commonly encountered in transgender population, may negatively influence the adherence to screening programs. Current cancer screening guidelines for this population are somewhat unclear, and specific programs based on more robust data are urgently required along with further tailored studies.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241259466"},"PeriodicalIF":4.3,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917486","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}
Neuroendocrine prostate cancer (NEPC) is a highly aggressive variant of castration-resistant prostate cancer. It is characterized by low or no expression of the androgen receptor (AR), activation of AR-independent signaling, and increased neuroendocrine phenotype. Most of NEPC is induced by treatment of androgen deprivation therapy and androgen receptor pathway inhibitors (ARPIs). Currently, the treatment of NEPC follows the treatment strategy for small-cell lung cancer, lacking effective drugs and specific treatment options. This review summarizes potential novel targets and therapies for NEPC treatment, including epigenetic regulators (zeste homolog 2 inhibitors, lysine-specific demethylase 1 inhibitors), aurora kinase A inhibitors, poly-ADP-ribose polymerase inhibitors, delta-like ligand 3 targeted therapies, a combination of immunotherapies, etc. Other promising targets and future directions are also discussed in this review. These novel targets and therapies may provide new opportunities for the treatment of NEPC.
{"title":"Promising therapy for neuroendocrine prostate cancer: current status and future directions.","authors":"Xin Fei, Jia-Wei Xue, Ji-Zhongrong Wu, Chong-Yi Yang, Ke-Jie Wang, Qi Ma","doi":"10.1177/17588359241269676","DOIUrl":"10.1177/17588359241269676","url":null,"abstract":"<p><p>Neuroendocrine prostate cancer (NEPC) is a highly aggressive variant of castration-resistant prostate cancer. It is characterized by low or no expression of the androgen receptor (AR), activation of AR-independent signaling, and increased neuroendocrine phenotype. Most of NEPC is induced by treatment of androgen deprivation therapy and androgen receptor pathway inhibitors (ARPIs). Currently, the treatment of NEPC follows the treatment strategy for small-cell lung cancer, lacking effective drugs and specific treatment options. This review summarizes potential novel targets and therapies for NEPC treatment, including epigenetic regulators (zeste homolog 2 inhibitors, lysine-specific demethylase 1 inhibitors), aurora kinase A inhibitors, poly-ADP-ribose polymerase inhibitors, delta-like ligand 3 targeted therapies, a combination of immunotherapies, etc. Other promising targets and future directions are also discussed in this review. These novel targets and therapies may provide new opportunities for the treatment of NEPC.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241269676"},"PeriodicalIF":4.3,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11311189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917487","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}
Background: Tumor necrosis (TN) is a common feature in lung squamous cell carcinoma (LSCC), which could provide useful predictive and prognostic information.
Objectives: This study aimed to investigate the effect of pretreatment pulmonary TN (PTN) on the prognosis of first-line anti-programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) inhibitor in advanced LSCC.
Design: We conducted a retrospective study to analyze the association between the presence of PTN and clinical outcomes in advanced LSCC patients treated with anti-PD-1/PD-L1 inhibitors.
Methods: Data from 240 eligible patients were collected from 27 hospitals across China between 2016 and 2020. The presence of PTN was assessed using contrast-enhanced chest computed tomography (CT) imaging at baseline. We utilized the Cox proportional-hazards regression model to analyze the association between PTN and clinical outcomes. In addition, to account for potential confounding factors and ensure comparability between groups, we employed propensity score-matching (PSM) analysis.
Results: In the overall patient cohort, the presence of PTN was 39.6%. The median follow-up duration was 20.3 months. The positive PTN group exhibited a notably inferior median progression-free survival (PFS; 6.5 months vs 8.6 months, p = 0.012) compared to the negative PTN group. Within the Cox proportional-hazards regression model, PTN emerged as an independent predictor of unfavorable PFS (hazard ratio (HR) = 1.354, 95% confidence interval (CI): 1.002-1.830, p = 0.049). After PSM, the median PFS for the positive PTN group (6.5 months vs 8.0 months, p = 0.027) remained worse than that of the negative PTN group. Multivariate analyses also further underscored that the presence of PTN independently posed a risk for shorter PFS (HR = 1.494, 95% CI: 1.056-2.112, p = 0.023). However, no statistically significant difference in overall survival was observed between the two groups.
Conclusion: Our study suggests that the presence of PTN on baseline contrast-enhanced chest CT is a potential negative prognostic imaging biomarker for the outcome of anti-PD-1/PD-L1 inhibitor therapy in advanced LSCC. Further studies are warranted to validate these findings and explore the underlying mechanisms.
{"title":"Pretreatment pulmonary tumor necrosis is a promising prognostic imaging biomarker for first-line anti-PD-1/PD-L1 therapy in advanced lung squamous cell carcinoma: a multi-institutional, propensity score-matching cohort analysis.","authors":"Qiaofeng Zhong, Longfeng Zhang, Lin Wu, Jun Zhao, Jianguo Sun, Yong Fang, Jin Zhou, Qian Chu, Yihong Shen, Zhenzhou Yang, Lijin Chen, Meijuan Huang, Xiaoyan Lin, Zhenhua Liu, Peng Shen, Zhijie Wang, Xin Wang, Huijuan Wang, Chengbo Han, Anwen Liu, Hongmei Zhang, Feng Ye, Wen Gao, Fang Wu, Zhengbo Song, Shengchi Chen, Chengzhi Zhou, Dingzhi Huang, Qiuyu Zhang, Xinlong Zheng, Xiaobin Zheng, Qian Miao, Kan Jiang, Zihua Zou, Yiquan Xu, Shiwen Wu, Haibo Wang, Yaping Hong, Tao Lu, Chao Li, Cheng Huang, Chuanben Chen, Gen Lin","doi":"10.1177/17588359241266188","DOIUrl":"10.1177/17588359241266188","url":null,"abstract":"<p><strong>Background: </strong>Tumor necrosis (TN) is a common feature in lung squamous cell carcinoma (LSCC), which could provide useful predictive and prognostic information.</p><p><strong>Objectives: </strong>This study aimed to investigate the effect of pretreatment pulmonary TN (PTN) on the prognosis of first-line anti-programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) inhibitor in advanced LSCC.</p><p><strong>Design: </strong>We conducted a retrospective study to analyze the association between the presence of PTN and clinical outcomes in advanced LSCC patients treated with anti-PD-1/PD-L1 inhibitors.</p><p><strong>Methods: </strong>Data from 240 eligible patients were collected from 27 hospitals across China between 2016 and 2020. The presence of PTN was assessed using contrast-enhanced chest computed tomography (CT) imaging at baseline. We utilized the Cox proportional-hazards regression model to analyze the association between PTN and clinical outcomes. In addition, to account for potential confounding factors and ensure comparability between groups, we employed propensity score-matching (PSM) analysis.</p><p><strong>Results: </strong>In the overall patient cohort, the presence of PTN was 39.6%. The median follow-up duration was 20.3 months. The positive PTN group exhibited a notably inferior median progression-free survival (PFS; 6.5 months vs 8.6 months, <i>p</i> = 0.012) compared to the negative PTN group. Within the Cox proportional-hazards regression model, PTN emerged as an independent predictor of unfavorable PFS (hazard ratio (HR) = 1.354, 95% confidence interval (CI): 1.002-1.830, <i>p</i> = 0.049). After PSM, the median PFS for the positive PTN group (6.5 months vs 8.0 months, <i>p</i> = 0.027) remained worse than that of the negative PTN group. Multivariate analyses also further underscored that the presence of PTN independently posed a risk for shorter PFS (HR = 1.494, 95% CI: 1.056-2.112, <i>p</i> = 0.023). However, no statistically significant difference in overall survival was observed between the two groups.</p><p><strong>Conclusion: </strong>Our study suggests that the presence of PTN on baseline contrast-enhanced chest CT is a potential negative prognostic imaging biomarker for the outcome of anti-PD-1/PD-L1 inhibitor therapy in advanced LSCC. Further studies are warranted to validate these findings and explore the underlying mechanisms.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241266188"},"PeriodicalIF":4.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11301739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898287","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 : 2024-08-02eCollection Date: 2024-01-01DOI: 10.1177/17588359241266179
J Robert Beecroft, Savtaj Brar, Xiaolan Feng, Trevor Hamilton, Cheng Han-Lee, Jan-Willem Henning, P David Josephy, Korosh Khalili, Yoo-Joung Ko, Christopher Lemieux, David M Liu, D Blair MacDonald, Jonathan Noujaim, Aaron Pollett, Abdulazeez Salawu, Ramy Saleh, Alannah Smrke, Blair E Warren, Kevin Zbuk, Albiruni Abdul Razak
Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours that originate from the interstitial cells of Cajal. GISTs are mainly driven by gain-of-function mutations in receptor tyrosine kinase or platelet-derived growth factor receptor alpha. Surgical resection is the only curative treatment for localized tumours and all currently approved medical GIST treatments are based on orally available tyrosine kinase inhibitors. Recent discoveries in the molecular and clinical features of GISTs have greatly impacted GIST management. Due to the provincially rather than nationally administered Canadian healthcare system, there have been inconsistencies in the treatment of GISTs across the country. Therefore, guidance on the latest knowledge, clinical management and treatment of GIST is needed to standardize the approach to GIST management nationwide. To establish pan-Canadian guidance, provide up-to-date data and harmonize the clinical practice of GIST management in high- and low-throughput centres across Canada; a panel of 20 physicians with extensive clinical experience in GIST management reviewed relevant literature. This included radiologists, pathologists, interventional radiologists, surgeons and medical oncologists across Canada. The structured literature focused on seven key domains: molecular profiling, radiological techniques/reporting, targeted localized therapy, intricacies of systemic treatments, emerging tests, multidisciplinary care and patient advocacy. This literature review, along with clinical expertise and opinion, was used to develop this concise and clinically relevant consensus paper to harmonize the knowledge and clinical practice on GIST management across Canada. The content presented here will help guide healthcare providers, especially in Canada, in terms of approaching and managing GIST.
{"title":"Pan-Canadian consensus recommendations for GIST management in high- and low-throughput centres across Canada.","authors":"J Robert Beecroft, Savtaj Brar, Xiaolan Feng, Trevor Hamilton, Cheng Han-Lee, Jan-Willem Henning, P David Josephy, Korosh Khalili, Yoo-Joung Ko, Christopher Lemieux, David M Liu, D Blair MacDonald, Jonathan Noujaim, Aaron Pollett, Abdulazeez Salawu, Ramy Saleh, Alannah Smrke, Blair E Warren, Kevin Zbuk, Albiruni Abdul Razak","doi":"10.1177/17588359241266179","DOIUrl":"10.1177/17588359241266179","url":null,"abstract":"<p><p>Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours that originate from the interstitial cells of Cajal. GISTs are mainly driven by gain-of-function mutations in receptor tyrosine kinase or platelet-derived growth factor receptor alpha. Surgical resection is the only curative treatment for localized tumours and all currently approved medical GIST treatments are based on orally available tyrosine kinase inhibitors. Recent discoveries in the molecular and clinical features of GISTs have greatly impacted GIST management. Due to the provincially rather than nationally administered Canadian healthcare system, there have been inconsistencies in the treatment of GISTs across the country. Therefore, guidance on the latest knowledge, clinical management and treatment of GIST is needed to standardize the approach to GIST management nationwide. To establish pan-Canadian guidance, provide up-to-date data and harmonize the clinical practice of GIST management in high- and low-throughput centres across Canada; a panel of 20 physicians with extensive clinical experience in GIST management reviewed relevant literature. This included radiologists, pathologists, interventional radiologists, surgeons and medical oncologists across Canada. The structured literature focused on seven key domains: molecular profiling, radiological techniques/reporting, targeted localized therapy, intricacies of systemic treatments, emerging tests, multidisciplinary care and patient advocacy. This literature review, along with clinical expertise and opinion, was used to develop this concise and clinically relevant consensus paper to harmonize the knowledge and clinical practice on GIST management across Canada. The content presented here will help guide healthcare providers, especially in Canada, in terms of approaching and managing GIST.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241266179"},"PeriodicalIF":4.3,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393607","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 : 2024-08-01eCollection Date: 2024-01-01DOI: 10.1177/17588359241265222
Ekaterina Kim, Natalia Kalinchenko, Anna Eremkina, Liliya Urusova, Rustam Salimkhanov, Natalia Mokrysheva
Parathyroid carcinoma (PC) is extremely rare in children and adolescent. PC is more often sporadic, but also it could be associated with germline mutations. The clinical features of primary hyperparathyroidism (PHPT) are nonspecific in children and adolescent, which delays the diagnosis for years. This case of PC in a pediatric patient, caused by germline heterozygous pathogenic variant in exon 1 of the CDC73 gene (c.70 G > T, p. Glu24Ter) is the first to be reported in Russia. Due to the rarity of pediatric parathyroid malignancy, the diagnosis of this endocrine neoplasm remains a challenge. The main difficulties that we faced in the management of the patient were the morphological confirmation of diagnosis, multiple surgical interventions, and disseminated PC metastases. We describe a 13-year-old girl with delayed diagnosis of PC and subsequent local recurrence after several surgeries, who underwent specific radiation therapy that allowed controlling hypercalcemia.
甲状旁腺癌(PC)在儿童和青少年中极为罕见。PC多为散发性,但也可能与种系突变有关。原发性甲状旁腺功能亢进症(PHPT)在儿童和青少年中的临床特征并无特异性,因此延误诊断多年。本例儿童患者的PC病因是CDC73基因第1外显子的种系杂合致病变异(c.70 G > T, p. Glu24Ter),这在俄罗斯尚属首次报道。由于小儿甲状旁腺恶性肿瘤的罕见性,这种内分泌肿瘤的诊断仍然是一项挑战。我们在处理该患者时遇到的主要困难是形态学确诊、多次手术干预和PC转移扩散。我们描述了一名 13 岁女孩的病例,她的 PC 诊断被延迟,随后在多次手术后局部复发,她接受了特殊的放射治疗,从而控制了高钙血症。
{"title":"Combination approach for <i>CDC73</i>-related parathyroid carcinoma in an adolescent female patient: a case report and literature review.","authors":"Ekaterina Kim, Natalia Kalinchenko, Anna Eremkina, Liliya Urusova, Rustam Salimkhanov, Natalia Mokrysheva","doi":"10.1177/17588359241265222","DOIUrl":"10.1177/17588359241265222","url":null,"abstract":"<p><p>Parathyroid carcinoma (PC) is extremely rare in children and adolescent. PC is more often sporadic, but also it could be associated with germline mutations. The clinical features of primary hyperparathyroidism (PHPT) are nonspecific in children and adolescent, which delays the diagnosis for years. This case of PC in a pediatric patient, caused by germline heterozygous pathogenic variant in exon 1 of the <i>CDC73</i> gene (c.70 G > T, p. Glu24Ter) is the first to be reported in Russia. Due to the rarity of pediatric parathyroid malignancy, the diagnosis of this endocrine neoplasm remains a challenge. The main difficulties that we faced in the management of the patient were the morphological confirmation of diagnosis, multiple surgical interventions, and disseminated PC metastases. We describe a 13-year-old girl with delayed diagnosis of PC and subsequent local recurrence after several surgeries, who underwent specific radiation therapy that allowed controlling hypercalcemia.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241265222"},"PeriodicalIF":4.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11295221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890138","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 : 2024-07-31eCollection Date: 2024-01-01DOI: 10.1177/17588359241266156
Puyi He, Long Ma, Bo Xu, Yunpeng Wang, Xiaomei Li, Hao Chen, Yumin Li
In recent years, with the continuous development of molecular immunology, immune checkpoint inhibitors (ICIs) have also been widely used in the treatment of gastric cancer, but they still face some challenges: The first is that only some people can benefit, the second is the treatment-related adverse events (TRAEs) that occur during treatment, and the third is the emergence of varying degrees of drug resistance with long-term use. How to overcome these challenges, combined therapy based on ICIs has become one of the important strategies. This article summarizes the clinical application of ICIs combined with chemotherapy, targeted therapy, radiotherapy, photodynamic therapy, thermotherapy, immune adjuvant, and dual immunotherapy and discusses the mechanism, and also summarizes the advantages and disadvantages of the current combination modalities and the potential research value. The aim of this study is to provide more and more optimized combination regimen for ICI combined therapy in patients with advanced gastric cancer and to provide reference for clinical and scientific research.
{"title":"Research progress and future directions of immune checkpoint inhibitor combination therapy in advanced gastric cancer.","authors":"Puyi He, Long Ma, Bo Xu, Yunpeng Wang, Xiaomei Li, Hao Chen, Yumin Li","doi":"10.1177/17588359241266156","DOIUrl":"10.1177/17588359241266156","url":null,"abstract":"<p><p>In recent years, with the continuous development of molecular immunology, immune checkpoint inhibitors (ICIs) have also been widely used in the treatment of gastric cancer, but they still face some challenges: The first is that only some people can benefit, the second is the treatment-related adverse events (TRAEs) that occur during treatment, and the third is the emergence of varying degrees of drug resistance with long-term use. How to overcome these challenges, combined therapy based on ICIs has become one of the important strategies. This article summarizes the clinical application of ICIs combined with chemotherapy, targeted therapy, radiotherapy, photodynamic therapy, thermotherapy, immune adjuvant, and dual immunotherapy and discusses the mechanism, and also summarizes the advantages and disadvantages of the current combination modalities and the potential research value. The aim of this study is to provide more and more optimized combination regimen for ICI combined therapy in patients with advanced gastric cancer and to provide reference for clinical and scientific research.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241266156"},"PeriodicalIF":4.3,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11292724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876048","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 : 2024-07-31eCollection Date: 2024-01-01DOI: 10.1177/17588359241265209
Minkwan Cho, Eunkyung Park, Yong-Pyo Lee, Hongsik Kim, Hee Sue Park, Hee Kyung Kim, Yaewon Yang, Jihyun Kwon, Ki Hyeong Lee, Hye Sook Han
Background: Esophagogastric and pancreaticobiliary cancers are associated with chronic blood loss, poor nutrition, and surgical interventions that interfere with iron absorption. Patients with these cancers often have a higher incidence of chemotherapy-induced anemia (CIA) than patients with other malignancies.
Objectives: To investigate the efficacy of intravenous iron or erythropoietin-stimulating agents (ESA) for CIA treatment in patients with esophagogastric or pancreaticobiliary cancer.
Design: Retrospective, comparative chart review of patients with esophagogastric or pancreaticobiliary cancer who received ferric carboxymaltose (FCM), or darbepoetin alfa (DA), and myelosuppressive chemotherapy at Chungbuk National University Hospital between June 2018 and December 2022.
Methods: To assess the efficacy of FCM or DA over time, data on hemoglobin (Hb) levels were collected from the time of administration of FCM or DA (baseline) until 6 months post-baseline, when available.
Results: In total, 214 patients (124 in the FCM and 90 in the DA group) were included in the analysis. The FCM group had a higher maximum Hb level and Hb changes for 3 months (mean ± standard deviation) following FCM or DA administration from baseline than the DA group (11.3 ± 1.5 versus 10.9 ± 1.2 g/dL, p = 0.02 and 2.0 ± 1.4 versus 1.5 ± 1.1 g/dL, p = 0.004, respectively). The FCM group had a higher proportion of Hb responders than the DA group (83.9% versus 68.9%, p = 0.013). Based on multivariable analysis, only the CIA treatment group was a significant factor for Hb response (odds ratio = 2.06, 95% confidence interval = 1.05-4.06, p = 0.036).
Conclusion: Both FCM and DA are effective, and FCM showed a higher Hb response than DA for CIA treatment in patients with esophagogastric or pancreaticobiliary cancer. Therefore, further randomized controlled trials should determine the optimal treatment for CIA in patients with these cancers undergoing myelosuppressive chemotherapy.
背景:食管胃癌和胰胆管癌与长期失血、营养不良以及影响铁吸收的手术干预有关。与其他恶性肿瘤患者相比,这些癌症患者的化疗诱发性贫血(CIA)发生率往往更高:研究静脉注射铁剂或促红细胞生成素(ESA)治疗食管胃癌或胰胆管癌患者 CIA 的疗效:对2018年6月至2022年12月期间在忠北国立大学医院接受羧甲基亚铁(FCM)或达贝泊汀α(DA)和骨髓抑制性化疗的食管胃癌或胰胆管癌患者进行回顾性、比较性病历审查:为评估FCM或DA随时间推移的疗效,收集了从服用FCM或DA时(基线)到基线后6个月的血红蛋白(Hb)水平数据(如有):共有 214 名患者(124 名 FCM 组和 90 名 DA 组)被纳入分析。与 DA 组相比,FCM 组的最大 Hb 水平更高,从基线开始服用 FCM 或 DA 后 3 个月的 Hb 变化(平均值 ± 标准差)也更大(分别为 11.3 ± 1.5 对 10.9 ± 1.2 g/dL,p = 0.02 和 2.0 ± 1.4 对 1.5 ± 1.1 g/dL,p = 0.004)。FCM 组的血红蛋白应答者比例高于 DA 组(83.9% 对 68.9%,p = 0.013)。根据多变量分析,只有 CIA 治疗组是影响 Hb 反应的重要因素(几率比 = 2.06,95% 置信区间 = 1.05-4.06,p = 0.036):结论:FCM 和 DA 均有效,在食管胃癌或胰胆管癌患者的 CIA 治疗中,FCM 比 DA 显示出更高的 Hb 反应。因此,应进一步开展随机对照试验,以确定对接受骨髓抑制性化疗的这些癌症患者进行 CIA 治疗的最佳方法。
{"title":"Efficacy of ferric carboxymaltose or darbepoetin alfa for chemotherapy-induced anemia in patients with esophagogastric or pancreaticobiliary cancer: a retrospective comparative study.","authors":"Minkwan Cho, Eunkyung Park, Yong-Pyo Lee, Hongsik Kim, Hee Sue Park, Hee Kyung Kim, Yaewon Yang, Jihyun Kwon, Ki Hyeong Lee, Hye Sook Han","doi":"10.1177/17588359241265209","DOIUrl":"10.1177/17588359241265209","url":null,"abstract":"<p><strong>Background: </strong>Esophagogastric and pancreaticobiliary cancers are associated with chronic blood loss, poor nutrition, and surgical interventions that interfere with iron absorption. Patients with these cancers often have a higher incidence of chemotherapy-induced anemia (CIA) than patients with other malignancies.</p><p><strong>Objectives: </strong>To investigate the efficacy of intravenous iron or erythropoietin-stimulating agents (ESA) for CIA treatment in patients with esophagogastric or pancreaticobiliary cancer.</p><p><strong>Design: </strong>Retrospective, comparative chart review of patients with esophagogastric or pancreaticobiliary cancer who received ferric carboxymaltose (FCM), or darbepoetin alfa (DA), and myelosuppressive chemotherapy at Chungbuk National University Hospital between June 2018 and December 2022.</p><p><strong>Methods: </strong>To assess the efficacy of FCM or DA over time, data on hemoglobin (Hb) levels were collected from the time of administration of FCM or DA (baseline) until 6 months post-baseline, when available.</p><p><strong>Results: </strong>In total, 214 patients (124 in the FCM and 90 in the DA group) were included in the analysis. The FCM group had a higher maximum Hb level and Hb changes for 3 months (mean ± standard deviation) following FCM or DA administration from baseline than the DA group (11.3 ± 1.5 <i>versus</i> 10.9 ± 1.2 g/dL, <i>p</i> = 0.02 and 2.0 ± 1.4 <i>versus</i> 1.5 ± 1.1 g/dL, <i>p</i> = 0.004, respectively). The FCM group had a higher proportion of Hb responders than the DA group (83.9% <i>versus</i> 68.9%, <i>p</i> = 0.013). Based on multivariable analysis, only the CIA treatment group was a significant factor for Hb response (odds ratio = 2.06, 95% confidence interval = 1.05-4.06, <i>p</i> = 0.036).</p><p><strong>Conclusion: </strong>Both FCM and DA are effective, and FCM showed a higher Hb response than DA for CIA treatment in patients with esophagogastric or pancreaticobiliary cancer. Therefore, further randomized controlled trials should determine the optimal treatment for CIA in patients with these cancers undergoing myelosuppressive chemotherapy.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241265209"},"PeriodicalIF":4.3,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11292682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876046","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 : 2024-07-31eCollection Date: 2024-01-01DOI: 10.1177/17588359241265214
Kun Wang, Hang Yi, Zhuoheng Lv, Donghui Jin, Li Fu, Yousheng Mao
Background: Neoadjuvant therapy improves survival benefits in patients with locally advanced non-small cell lung cancer but increases tissue density, presenting challenges for surgeons.
Objectives: To compare the differences in surgical complexity and short-term prognostic outcomes between neoadjuvant targeted therapy (NTT) and neoadjuvant chemoimmunotherapy (NCI).
Design/methods: This study enrolled 106 patients underwent curative surgery after neoadjuvant therapy between January 2020 and December 2023 at the National Cancer Center of China. Differences in surgical complexity and short-term prognostic outcomes between the two neoadjuvant therapy cohorts were evaluated. The pathological indicators such as pathological response rate and lymph node upstaging/downstaging were then analyzed.
Results: In total, 33 patients underwent NTT and 73 underwent NCI preoperatively. Patients who received NTT showed a higher minimally invasive surgery rate (84.8% versus 53.4%, p < 0.01), shorter operative time (144 versus 184 min, p < 0.01), lower conversion rate (3.3% versus 17.8%, p = 0.03), less postoperative drainage (day 3: 140 versus 200 mL, p = 0.03), and lower incidence of postoperative complications including arrhythmias (6.1% versus 26%, p = 0.02). The pathological response rate in the NTT and NCI groups was 70% and 75%, respectively, with the latter group showing a higher complete pathological response rate. The two groups had no significant differences in major pathological response and lymph node pathological response rate.
Conclusion: Patients who received NTT presented fewer surgical challenges for surgeons and had better surgical outcomes than those who received NCI therapy, with comparable pathological response rates between the two cohorts. Accordingly, NTT is the preferred induction regimen for patients harboring mutation status.
{"title":"Analysis of surgical complexity and short-term prognostic indicators in NSCLC patients: neoadjuvant targeted therapy <i>versus</i> neoadjuvant chemoimmunotherapy.","authors":"Kun Wang, Hang Yi, Zhuoheng Lv, Donghui Jin, Li Fu, Yousheng Mao","doi":"10.1177/17588359241265214","DOIUrl":"10.1177/17588359241265214","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant therapy improves survival benefits in patients with locally advanced non-small cell lung cancer but increases tissue density, presenting challenges for surgeons.</p><p><strong>Objectives: </strong>To compare the differences in surgical complexity and short-term prognostic outcomes between neoadjuvant targeted therapy (NTT) and neoadjuvant chemoimmunotherapy (NCI).</p><p><strong>Design/methods: </strong>This study enrolled 106 patients underwent curative surgery after neoadjuvant therapy between January 2020 and December 2023 at the National Cancer Center of China. Differences in surgical complexity and short-term prognostic outcomes between the two neoadjuvant therapy cohorts were evaluated. The pathological indicators such as pathological response rate and lymph node upstaging/downstaging were then analyzed.</p><p><strong>Results: </strong>In total, 33 patients underwent NTT and 73 underwent NCI preoperatively. Patients who received NTT showed a higher minimally invasive surgery rate (84.8% <i>versus</i> 53.4%, <i>p</i> < 0.01), shorter operative time (144 <i>versus</i> 184 min, <i>p</i> < 0.01), lower conversion rate (3.3% <i>versus</i> 17.8%, <i>p</i> = 0.03), less postoperative drainage (day 3: 140 <i>versus</i> 200 mL, <i>p</i> = 0.03), and lower incidence of postoperative complications including arrhythmias (6.1% <i>versus</i> 26%, <i>p</i> = 0.02). The pathological response rate in the NTT and NCI groups was 70% and 75%, respectively, with the latter group showing a higher complete pathological response rate. The two groups had no significant differences in major pathological response and lymph node pathological response rate.</p><p><strong>Conclusion: </strong>Patients who received NTT presented fewer surgical challenges for surgeons and had better surgical outcomes than those who received NCI therapy, with comparable pathological response rates between the two cohorts. Accordingly, NTT is the preferred induction regimen for patients harboring mutation status.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241265214"},"PeriodicalIF":4.3,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11292697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876044","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}