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Early evaluation of the effectiveness and cost-effectiveness of ctDNA-guided selection for adjuvant chemotherapy in stage II colon cancer. ctDNA指导下选择II期结肠癌辅助化疗的有效性和成本效益的早期评估。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-08-21 eCollection Date: 2024-01-01 DOI: 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.

背景:目前,II期结肠癌(CC)根治术后辅助化疗(ACT)的患者选择并不理想,导致高危患者治疗过度,低危患者治疗不足。术后循环肿瘤 DNA(ctDNA)可改善 ACT 患者的选择:我们对荷兰 II 期 CC 在 ctDNA 指导下选择 ACT 的(成本)有效性进行了基于模型的早期评估,以评估具有成本效益的实施条件:一个经过验证的马尔可夫模型模拟了1000名II期CC患者从诊断到死亡的整个过程,并补充了ctDNA数据。评估了五种 ACT 选择策略:现行指南(pT4、pMMR)、纯 ctDNA 以及以不同方式将 ctDNA 状态与 pT4 和 pMMR 状态相结合的三种策略。对每种策略的成本、生命年、质量调整生命年 (QALY)、复发率和 CC 死亡率进行了估算。进行了敏感性分析,以评估ctDNA检测成本、策略依从性、ctDNA作为预测性生物标志物以及ctDNA检测性能的影响:结果:模型预测显示,与现行指南相比,纯 ctDNA 策略的效果较差(复发率 +2.2%,-0.016 QALYs),而组合策略的效果较好(复发率 -3.6%,+0.038 QALYs)。由于增量成本效益比为每 QALY 67,413 欧元,超过了每 QALY 50,000 欧元的支付意愿阈值,因此联合疗法不具成本效益。敏感性分析表明,如果ctDNA检测成本低于1500欧元,或ctDNA状态可预测治疗反应,或ctDNA检测性能大幅提高,那么联合策略将具有成本效益:结论:在目前的高风险临床病理特征(pT4 和 pMMR)基础上增加 ctDNA 可改善 ACT 患者的选择,也可能具有成本效益。未来的研究应调查手术后ctDNA状态的预测价值,以准确评估ctDNA检测在II期CC的ACT决策中的成本效益。
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引用次数: 0
Strategies to overcome tumor microenvironment immunosuppressive effect on the functioning of CAR-T cells in high-grade glioma. 克服肿瘤微环境对 CAR-T 细胞在高级别胶质瘤中发挥作用的免疫抑制作用的策略。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-08-15 eCollection Date: 2024-01-01 DOI: 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.

尽管某些类型癌症的治疗取得了重大进展,但高级别胶质瘤(HGGs)仍然是一个严重的临床问题。胶质母细胞瘤(GBM)是成人中枢神经系统最常见的实体瘤,尽管采用了强化多模式疗法,但从确诊到存活的平均时间只有 15-18 个月。表达嵌合抗原受体(CAR)的 T 细胞已被美国食品和药物管理局批准用于治疗某些血液系统恶性肿瘤,是一种前景广阔的新疗法。然而,由于肿瘤微环境(TME)具有免疫抑制作用,CAR-T 细胞在实体瘤中的疗效较低。因此,将具有免疫抑制作用的肿瘤微环境重编程,使其趋向于促炎表型似乎尤为重要,因为这可以提高 CAR-T 细胞治疗实体瘤的疗效。下面的文献综述旨在介绍临床前研究的结果,这些结果表明,通过将 TME 重编程为促炎表型,有可能提高 CAR-T 在 GBM TME 中的疗效。CAR-T可以与溶瘤病毒、放疗或表观遗传抑制剂联合使用,也可以支持CAR-T细胞穿越血脑屏障,使TME中受损的血管生成正常化,通过细胞因子信号转导或阻断/敲除T细胞抑制剂以及调节microRNA的表达来改善CAR-T的效应功能。在协同治疗中使用经过这种方式修饰的 CAR-T 细胞,可以诱导内源性抗肿瘤反应,从而延长 HGG 患者的生存期。
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引用次数: 0
Breast and cervical cancer in transgender men: literature review and a case report. 变性男性的乳腺癌和宫颈癌:文献综述和病例报告。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-08-10 eCollection Date: 2024-01-01 DOI: 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.

变性人具有更高的癌症相关风险因素,如药物滥用和性传播感染。这些因素加上对癌症筛查建议的不完全遵守,可能会导致乳腺癌和宫颈癌等癌症的发病率升高,并造成变性患者的诊断延迟。在此,我们报告了一例独特的病例:一名有酗酒和吸毒史的变性人在接受性别确认外源性睾酮治疗后,患上了同步的局部晚期乳腺癌和与人乳头瘤病毒(HPV)相关的宫颈癌。他同时接受了宫颈癌化疗和乳腺癌手术及内分泌治疗。由于患者合并有肝硬化等疾病,治疗效果不理想,导致患者过早死亡。此外,我们还对现有文献进行了综述,包括病例报告、临床研究和综述文章,调查变性男性乳腺癌和宫颈肿瘤的潜在风险因素的作用。性别确认睾酮疗法在变性男性中很常见,以诱导性别确认,但其与乳腺癌风险的联系仍不明确,研究有限,有时甚至相互矛盾。相反,人乳头状瘤病毒是高达 99% 宫颈癌的公认病因。尽管保留宫颈的变性男性患宫颈癌的风险持续存在,但多项研究表明,由于个人和结构性障碍,在坚持筛查方面存在明显差异。此外,变性人群中常见的酗酒和吸毒障碍可能会对坚持筛查计划产生负面影响。目前针对这一人群的癌症筛查指南尚不明确,迫切需要基于更可靠数据的具体方案以及进一步的定制研究。
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引用次数: 0
Promising therapy for neuroendocrine prostate cancer: current status and future directions. 神经内分泌性前列腺癌的有望治疗:现状与未来方向。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-08-08 eCollection Date: 2024-01-01 DOI: 10.1177/17588359241269676
Xin Fei, Jia-Wei Xue, Ji-Zhongrong Wu, Chong-Yi Yang, Ke-Jie Wang, Qi Ma

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.

神经内分泌性前列腺癌(NEPC)是具有高度侵袭性的去势抵抗性前列腺癌变种。它的特点是雄激素受体(AR)表达量低或不表达、AR 信号依赖性激活以及神经内分泌表型增加。大多数 NEPC 是通过雄激素剥夺疗法和雄激素受体通路抑制剂(ARPIs)诱发的。目前,NEPC 的治疗遵循小细胞肺癌的治疗策略,缺乏有效的药物和特定的治疗方案。本综述总结了治疗NEPC的潜在新靶点和疗法,包括表观遗传调节剂(zeste同源物2抑制剂、赖氨酸特异性去甲基化酶1抑制剂)、极光激酶A抑制剂、聚ADP核糖聚合酶抑制剂、δ样配体3靶向疗法、免疫疗法组合等。本综述还讨论了其他有前景的靶点和未来发展方向。这些新型靶点和疗法可能会为治疗 NEPC 提供新的机会。
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引用次数: 0
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. 治疗前肺肿瘤坏死是晚期肺鳞状细胞癌一线抗PD-1/PD-L1治疗的一种有希望的预后成像生物标志物:一项多机构倾向得分匹配队列分析。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-08-05 eCollection Date: 2024-01-01 DOI: 10.1177/17588359241266188
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

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.

背景:肿瘤坏死(TN)是肺鳞癌(LSCC)的常见特征:肿瘤坏死(TN)是肺鳞癌(LSCC)的常见特征,可提供有用的预测和预后信息:本研究旨在探讨治疗前肺TN(PTN)对晚期LSCC一线抗程序性细胞死亡1(PD-1)/PD配体1(PD-L1)抑制剂预后的影响:我们开展了一项回顾性研究,分析PTN的存在与接受抗PD-1/PD-L1抑制剂治疗的晚期LSCC患者临床预后之间的关系:2016年至2020年间,我们从全国27家医院收集了240名符合条件的患者数据。基线时使用对比增强胸部计算机断层扫描(CT)成像评估是否存在PTN。我们采用 Cox 比例危险回归模型来分析 PTN 与临床结局之间的关系。此外,为了考虑潜在的混杂因素并确保组间的可比性,我们采用了倾向得分匹配(PSM)分析:结果:在整个患者队列中,PTN的出现率为39.6%。中位随访时间为 20.3 个月。与阴性 PTN 组相比,阳性 PTN 组的中位无进展生存期(PFS;6.5 个月 vs 8.6 个月,P = 0.012)明显较低。在 Cox 比例危险回归模型中,PTN 成为不利 PFS 的独立预测因子(危险比 (HR) = 1.354,95% 置信区间 (CI):1.002-1.830,p = 0.049)。PSM 后,PTN 阳性组的中位 PFS(6.5 个月 vs 8.0 个月,p = 0.027)仍比 PTN 阴性组差。多变量分析还进一步强调,PTN 的存在会导致较短的 PFS(HR = 1.494,95% CI:1.056-2.112,p = 0.023)。然而,两组患者的总生存期在统计学上没有明显差异:我们的研究表明,基线对比增强胸部 CT 上 PTN 的存在是晚期 LSCC 抗 PD-1/PD-L1 抑制剂治疗结果的潜在阴性预后影像生物标志物。有必要开展进一步研究,以验证这些发现并探索其潜在机制。
{"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}
引用次数: 0
Pan-Canadian consensus recommendations for GIST management in high- and low-throughput centres across Canada. 加拿大各地高通量和低通量中心对 GIST 管理的泛加拿大共识建议。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-08-02 eCollection Date: 2024-01-01 DOI: 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.

胃肠间质瘤(GIST)是一种间质肿瘤,起源于卡贾尔间质细胞。胃肠间质瘤主要由受体酪氨酸激酶或血小板衍生生长因子受体α的功能增益突变引起。手术切除是治疗局部肿瘤的唯一根治方法,目前所有获批的 GIST 药物治疗均以口服酪氨酸激酶抑制剂为基础。GIST 的分子和临床特征方面的最新发现极大地影响了 GIST 的治疗。由于加拿大的医疗保健系统由各省而非全国管理,因此全国各地对 GIST 的治疗方法不尽相同。因此,有必要就 GIST 的最新知识、临床管理和治疗提供指导,以便在全国范围内统一 GIST 的管理方法。为了制定泛加拿大指南、提供最新数据并协调加拿大各地高通量和低通量中心的 GIST 管理临床实践,一个由 20 名在 GIST 管理方面具有丰富临床经验的医生组成的小组对相关文献进行了审查。小组成员包括加拿大各地的放射科医生、病理科医生、介入放射科医生、外科医生和肿瘤内科医生。结构化文献主要集中在七个关键领域:分子剖析、放射技术/报告、有针对性的局部治疗、复杂的全身治疗、新兴检测、多学科护理和患者权益维护。通过文献综述以及临床专业知识和意见,我们编写了这份简明扼要且与临床相关的共识文件,以协调加拿大各地有关 GIST 管理的知识和临床实践。本文介绍的内容将有助于指导医疗服务提供者(尤其是加拿大的医疗服务提供者)如何处理和管理 GIST。
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引用次数: 0
Combination approach for CDC73-related parathyroid carcinoma in an adolescent female patient: a case report and literature review. 青少年女性患者 CDC73 相关性甲状旁腺癌的综合治疗方法:病例报告和文献综述。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-08-01 eCollection Date: 2024-01-01 DOI: 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。
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引用次数: 0
Research progress and future directions of immune checkpoint inhibitor combination therapy in advanced gastric cancer. 免疫检查点抑制剂联合疗法在晚期胃癌中的研究进展和未来方向。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-07-31 eCollection Date: 2024-01-01 DOI: 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.

近年来,随着分子免疫学的不断发展,免疫检查点抑制剂(ICIs)也被广泛应用于胃癌的治疗,但仍面临一些挑战:一是只有部分人能够获益,二是治疗过程中会出现治疗相关不良事件(TRAEs),三是长期使用会出现不同程度的耐药性。如何克服这些挑战,基于 ICIs 的联合疗法已成为重要策略之一。本文总结了ICIs与化疗、靶向治疗、放疗、光动力治疗、热疗、免疫辅助、双重免疫治疗等联合治疗的临床应用情况,探讨了其机制,并总结了目前联合治疗方式的优缺点及潜在的研究价值。本研究旨在为晚期胃癌患者的 ICI 联合治疗提供更多、更优化的联合方案,为临床和科研提供参考。
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引用次数: 0
Efficacy of ferric carboxymaltose or darbepoetin alfa for chemotherapy-induced anemia in patients with esophagogastric or pancreaticobiliary cancer: a retrospective comparative study. 食管胃癌或胰胆管癌患者化疗所致贫血的羧甲基亚铁或达贝泊汀α疗效:一项回顾性比较研究。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-07-31 eCollection Date: 2024-01-01 DOI: 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}
引用次数: 0
Analysis of surgical complexity and short-term prognostic indicators in NSCLC patients: neoadjuvant targeted therapy versus neoadjuvant chemoimmunotherapy. 新辅助靶向疗法与新辅助化疗免疫疗法:NSCLC 患者的手术复杂性和短期预后指标分析》(Analysis of surgical complexity and short-term progostic indicators in NSCLC patients: neoadjuvant targeted therapy versus neoadjuvant chemoimmunotherapy)。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-07-31 eCollection Date: 2024-01-01 DOI: 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.

背景:新辅助治疗可提高局部晚期非小细胞肺癌患者的生存率,但会增加组织密度,给外科医生带来挑战:比较新辅助靶向治疗(NTT)和新辅助化疗免疫治疗(NCI)在手术复杂性和短期预后结果方面的差异:本研究纳入了2020年1月至2023年12月期间在中国国家癌症中心接受新辅助治疗后进行根治性手术的106例患者。评估了两组新辅助治疗患者在手术复杂程度和短期预后方面的差异。然后分析病理指标,如病理反应率和淋巴结上/下分期:共有33名患者在术前接受了NTT治疗,73名患者在术前接受了NCI治疗。接受NTT的患者微创手术率更高(84.8%对53.4%,P<0.01),手术时间更短(144分钟对184分钟,P<0.01),转化率更低(3.3%对17.8%,P=0.03),术后引流量更少(第3天:140毫升对200毫升,P=0.03),术后并发症包括心律失常的发生率更低(6.1%对26%,P=0.02)。NTT 组和 NCI 组的病理反应率分别为 70% 和 75%,后者的完全病理反应率更高。两组的主要病理反应和淋巴结病理反应率无明显差异:结论:与接受NCI治疗的患者相比,接受NTT治疗的患者给外科医生带来的手术挑战更少,手术效果更好,两组患者的病理反应率相当。因此,NTT是突变状态患者的首选诱导方案。
{"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}
引用次数: 0
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Therapeutic Advances in Medical Oncology
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