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Early Urinary Potassium Level Predicts High-dose Methotrexate Elimination Delay in Primary Central Nervous System Lymphoma. 原发性中枢神经系统淋巴瘤患者早期尿钾水平可预测大剂量甲氨蝶呤的消除延迟
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.21873/anticanres.17272
Vincent Harlay, Alexandre Bertucci, Céline Boucard, Gregorio Petrirena, Chantal Campello, Maryline Barrié, Didier Autran, Olivier Chinot, Emeline Tabouret

Background/aim: Treatment of primary central nervous system lymphoma (PCNSL) includes high dose methotrexate-based polychemotherapy (HD-MTX). This study aimed to identify early predictive factors of methotrexate (MTX) delayed elimination.

Patients and methods: We prospectively included all patients with newly-diagnosed PCNSL. Daily serum and urinary creatinine and ionogram were collected. We generated two independent cohorts: a training cohort (TC) and a confirmatory cohort (CC).

Results: We included for analysis 64 cures of HD-MTX (20 patients) in the TC and 59 cures (22 patients) in the CC. Median elimination time of MTX was 95 h and 96 h in the TC and CC, respectively. In multivariate analysis, older age (p=0.004), low Karnofsky Performance Status (p=0.036) and high urinary K+ (p=0.001) were associated with delayed MTX elimination. An optimal cutoff for urinary K+ was defined. In the CC, we confirmed that high urinary K+ (p=0.004) remained associated with delayed MTX elimination.

Conclusion: High urinary K+ may be predictive of delayed MTX elimination in primary central nervous system lymphoma. Its relevance as a decision-making factor needs to be validated in additional prospective studies.

背景/目的:原发性中枢神经系统淋巴瘤(PCNSL)的治疗包括基于甲氨蝶呤的大剂量多化学疗法(HD-MTX)。本研究旨在确定甲氨蝶呤(MTX)延迟消除的早期预测因素:我们前瞻性地纳入了所有新诊断的 PCNSL 患者。收集每日血清肌酐、尿肌酐和离子图。我们建立了两个独立队列:训练队列(TC)和确诊队列(CC):结果:我们在 TC 中纳入了 64 例 HD-MTX 治愈患者(20 例)进行分析,在 CC 中纳入了 59 例治愈患者(22 例)进行分析。TC和CC中MTX的中位消除时间分别为95小时和96小时。在多变量分析中,年龄大(p=0.004)、卡诺夫斯基表现状态低(p=0.036)和尿 K+ 高(p=0.001)与 MTX 消除延迟有关。我们确定了尿 K+ 的最佳临界值。在CC中,我们证实高尿K+(p=0.004)仍与MTX消除延迟相关:结论:高尿 K+ 可预测原发性中枢神经系统淋巴瘤的 MTX 消退延迟。结论:高尿 K+ 可预测原发性中枢神经系统淋巴瘤的 MTX 消退延迟,但其作为决策因素的相关性还需要在更多的前瞻性研究中加以验证。
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引用次数: 0
Serum Inflammatory Dynamics as Novel Biomarkers for Immune Checkpoint Inhibitors in Non-small-cell Lung Cancer With Bone Metastases. 血清炎症动态作为骨转移非小细胞肺癌免疫检查点抑制剂的新型生物标记物
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.21873/anticanres.17278
Yohei Asano, Norio Yamamoto, Katsuhiro Hayashi, Akihiko Takeuchi, Satoshi Kato, Shinji Miwa, Miho Okuda, Isao Matsumoto, Seiji Yano, Satoru Demura

Background/aim: The aim of the study was to develop a novel predictive scoring system based on the dynamics of serum inflammatory indicators in immune checkpoint inhibitor (ICI) treatment on non-small-cell lung cancer (NSCLC) with bone metastases.

Patients and methods: Sixty patients with NSCLC and bone metastases treated with ICIs between January 2016 and March 2021 were included in the development cohort. Serum neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) levels were assessed before (pre-value) and 6 weeks after (post-value) ICI treatment, and a novel predictive score was developed: pre-value ≥ post-value, 0 points; pre-value < post-value, 1 point; total score: 0-2 points. The associations of these dynamics and the score with clinical outcomes, including overall survival (OS), progression-free survival (PFS), response rate (RR) of bone metastases, and disease control rate (DCR), were evaluated. Furthermore, cross-validation was performed with 23 patients after April 2021 using the same inclusion criteria.

Results: The patients with decreased serum inflammation levels had significantly better OS, PFS, and RR than those with increased levels. Applying the developed score to the development cohort, the patients with 0 points had significantly better OS, PFS, and RR than others. In multivariable analysis, the score independently predicted treatment response to ICI for bone metastasis and prognosis. Cross-validation showed that OS, PFS, and RR were significantly better in the patients in the 0-point group.

Conclusion: The early NLR and CRP dynamics were associated with therapeutic responses to ICIs in NSCLC with bone metastases. Our novel scoring system based on these dynamics is simple and has a high predictive accuracy.

背景/目的:该研究旨在开发一种基于免疫检查点抑制剂(ICI)治疗非小细胞肺癌(NSCLC)骨转移患者血清炎症指标动态的新型预测评分系统:在2016年1月至2021年3月期间接受ICIs治疗的60例NSCLC骨转移患者被纳入开发队列。评估了ICI治疗前(前值)和治疗后6周(后值)的血清中性粒细胞与淋巴细胞比值(NLR)和C反应蛋白(CRP)水平,并制定了新的预测评分:前值≥后值,0分;前值<后值,1分;总分:0-2分。研究人员评估了这些动态指标和评分与临床结果的关联,包括总生存期(OS)、无进展生存期(PFS)、骨转移反应率(RR)和疾病控制率(DCR)。此外,在2021年4月之后,采用相同的纳入标准对23名患者进行了交叉验证:结果:血清炎症水平降低的患者的OS、PFS和RRR明显优于炎症水平升高的患者。将所制定的评分应用于发展队列,0 分患者的 OS、PFS 和 RR 均明显优于其他患者。在多变量分析中,该评分能独立预测骨转移对 ICI 的治疗反应和预后。交叉验证显示,0分组患者的OS、PFS和RR明显更好:结论:早期NLR和CRP动态与NSCLC骨转移患者对ICI的治疗反应有关。我们基于这些动态变化的新型评分系统既简单又具有很高的预测准确性。
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引用次数: 0
Role of the Hippo-YAP/TAZ Pathway in Epithelioid Hemangioendothelioma and its Potential as a Therapeutic Target. Hippo-YAP/TAZ通路在上皮样血管内皮细胞瘤中的作用及其作为治疗靶点的潜力
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.21873/anticanres.17245
Hirotaka Suto

Epithelioid hemangioendothelioma (EHE) is a rare malignant vascular tumor arising from vascular endothelial cells. This study delves into the molecular mechanisms underlying EHE, with a specific focus on the Hippo-YAP/TAZ pathway. EHE is characterized molecularly by transcriptional co-activator with a PDZ-motif (TAZ)-calmodulin binding transcription activator 1 (CAMTA1) or Yes-associated protein (YAP)-transcription factor E3 (TFE3) fusions. YAP/TAZ, a transcription co-activator, binds to transcription factors and regulates gene expression. The YAP/TAZ and its upstream Hippo pathway are involved in cell proliferation and cell contact inhibition, regulating organ size and carcinogenesis. In addition to oncogenic effects, dysfunction or gene duplication of the Hippo pathway results in a poor prognosis due to epithelial-mesenchymal transformation of epithelial cells, stem cell transformation, and increased drug resistance. Notably, the TAZ-CAMTA1 fusion is specific to EHE, and genetic alterations in the Hippo pathway other than this fusion gene are absent in EHE. The TAZ-CAMTA1 fusion is a promising therapeutic target. This review summarizes recent advances in EHE, focusing on the role of the Hippo-YAP/TAZ pathway in EHE and its potential as a therapeutic target for drug development.

上皮样血管内皮细胞瘤(EHE)是一种罕见的血管内皮细胞恶性肿瘤。本研究深入探讨了 EHE 的分子机制,重点关注 Hippo-YAP/TAZ 通路。EHE的分子特征是带有PDZ-motif(TAZ)的转录共激活因子-钙调蛋白结合转录激活因子1(CAMTA1)或Yes-相关蛋白(YAP)-转录因子E3(TFE3)融合。YAP/TAZ是一种转录共激活因子,可与转录因子结合并调节基因表达。YAP/TAZ 及其上游 Hippo 通路参与细胞增殖和细胞接触抑制,调节器官大小和致癌作用。除了致癌作用外,Hippo 通路的功能障碍或基因重复也会导致上皮细胞的上皮-间质转化、干细胞转化和耐药性增强,从而导致不良预后。值得注意的是,TAZ-CAMTA1 融合基因是 EHE 的特异性基因,除该融合基因外,EHE 中不存在 Hippo 通路的基因改变。TAZ-CAMTA1 融合基因是一个很有前景的治疗靶点。本综述总结了 EHE 的最新进展,重点探讨了 Hippo-YAP/TAZ 通路在 EHE 中的作用及其作为药物开发治疗靶点的潜力。
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引用次数: 0
CD8-Positive T-Cells Are Key Immune Cells for Predicting the Therapeutic Effect of Neoadjuvant Chemotherapy in Triple-negative Breast Cancer. CD8阳性T细胞是预测三阴性乳腺癌新辅助化疗疗效的关键免疫细胞
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.21873/anticanres.17281
Natsuki Uenaka, Eiichi Sato, Yoshiya Horimoto, Saori Kawai, Mariko Asaoka, Hiroshi Kaise, Kimito Yamada, Takashi Ishikawa

Background/aim: Patients with triple-negative breast cancer (TNBC) who obtain a pathological complete response (pCR) after neoadjuvant chemotherapy have an improved prognosis. Lymphocyte-predominant breast cancer is more likely to respond to neoadjuvant chemotherapy. Here, we investigated the correlation between tumor-infiltrating lymphocytes (TILs) in pre-treatment biopsy specimens from patients with TNBC in relation to response to NAC.

Patients and methods: The level of infiltration by immune cells expressing immune cell lineage surface markers (CD8, CD4, CD19, CD14, CD11c, and CD11b) in biopsy specimens from 52 patients with TNBC was examined using multispectral immunofluorescent labelling.

Results: The level of CD8-positive TILs was significantly higher in patients with a pCR (p=0.045). The Cox proportional hazard model confirmed that lymph node involvement was associated with poorer disease-free survival (p=0.008). A high level of CD8-positive TILs was related to significantly prolonged disease-free survival in patients with node-positive TNBC (p=0.018).

Conclusion: Assessing infiltration by CD8-positive TILs in the primary tumor is a useful biomarker to predict pCR and improved outcome in patients with node-positive TNBC.

背景/目的:新辅助化疗后获得病理完全反应(pCR)的三阴性乳腺癌(TNBC)患者预后较好。淋巴细胞占优势的乳腺癌更有可能对新辅助化疗产生反应。在此,我们研究了TNBC患者治疗前活检标本中肿瘤浸润淋巴细胞(TILs)与新辅助化疗反应之间的相关性:采用多谱免疫荧光标记法检测了52例TNBC患者活检标本中表达免疫细胞系表面标记(CD8、CD4、CD19、CD14、CD11c和CD11b)的免疫细胞的浸润水平:结果:CD8阳性TIL的水平在pCR患者中明显更高(p=0.045)。Cox比例危险模型证实,淋巴结受累与较差的无病生存率相关(p=0.008)。高水平的CD8阳性TIL与结节阳性TNBC患者无病生存期显著延长有关(p=0.018):结论:评估CD8阳性TIL在原发肿瘤中的浸润是预测结节阳性TNBC患者pCR和改善预后的有用生物标志物。
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引用次数: 0
Safety and Efficacy of Durvalumab After Chemoradiotherapy in Antinuclear Antibody-positive Patients With Non-small Cell Lung Cancer. 抗核抗体阳性非小细胞肺癌患者化疗后使用 Durvalumab 的安全性和有效性
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.21873/anticanres.17280
Akihiro Tsukaguchi, Akihiro Tamiya, Shoichi Fukuda, Yuki Iwahashi, Kensuke Kanaoka, Yuya Tanaka, Yuji Inagaki, Yoshihiko Taniguchi, Keiko Nakao, Tomoko Kagawa, Yoshinobu Matsuda, Kyoichi Okishio

Background/aim: Pneumonitis during durvalumab consolidation therapy after chemoradiotherapy (CRT) is a major cause of treatment discontinuation. Although previous studies have revealed an association between antinuclear antibody (ANA) positivity and the safety and efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer (NSCLC), there are no reports on durvalumab consolidation therapy. This study investigated the safety and efficacy of durvalumab after CRT in ANA-positive patients.

Patients and methods: We retrospectively reviewed patients with unresectable NSCLC treated with durvalumab after CRT between August 2018 and July 2022 at our institution. We evaluated the association among ANA positivity, treatment-related adverse events (AEs), and survival outcomes.

Results: Overall, 80 patients were enrolled, 39 of whom were ANA-positive. Although there were no significant differences in the incidence of each AE of any grade, ANA-positive patients tended to have a higher frequency of pneumonitis of grade 3 to 5 than ANA-negative patients (12.8% vs. 2.4%, p=0.104). ANA-positive patients had a significantly shorter median progression-free survival (PFS) and overall survival (OS) than ANA-negative patients [14.9 months vs. not reached (NR), p=0.005; NR vs. NR, p=0.013]. Multivariate analysis revealed that ANA positivity was an independent predictor of shorter PFS (HR=2.23; 95% CI=1.16-4.29; p=0.016) and OS (HR=2.28; 95% CI=1.01-5.12; p=0.046).

Conclusion: ANA-positive patients receiving durvalumab after CRT tended to have a higher frequency of severe pneumonitis and significantly worse PFS and OS compared with ANA-negative patients.

背景/目的:在化放疗(CRT)后进行杜伐单抗巩固治疗期间出现肺炎是导致治疗中断的一个主要原因。尽管之前的研究显示抗核抗体(ANA)阳性与晚期非小细胞肺癌(NSCLC)免疫检查点抑制剂的安全性和疗效之间存在关联,但目前还没有关于durvalumab巩固治疗的报道。本研究调查了ANA阳性患者CRT后使用durvalumab的安全性和有效性:我们回顾性地回顾了2018年8月至2022年7月期间在我院接受CRT后使用度伐单抗治疗的不可切除NSCLC患者。我们评估了ANA阳性、治疗相关不良事件(AEs)和生存结果之间的关联:共有 80 名患者入组,其中 39 人 ANA 阳性。虽然各等级AE的发生率无明显差异,但ANA阳性患者发生3至5级肺炎的频率往往高于ANA阴性患者(12.8%对2.4%,P=0.104)。ANA阳性患者的中位无进展生存期(PFS)和总生存期(OS)明显短于ANA阴性患者[14.9个月 vs. 未达到(NR),p=0.005;NR vs. NR,p=0.013]。多变量分析显示,ANA阳性是较短PFS(HR=2.23;95% CI=1.16-4.29;P=0.016)和OS(HR=2.28;95% CI=1.01-5.12;P=0.046)的独立预测因素:结论:与ANA阴性患者相比,ANA阳性患者在CRT后接受度伐卢单抗治疗时,发生严重肺炎的频率更高,PFS和OS明显更差。
{"title":"Safety and Efficacy of Durvalumab After Chemoradiotherapy in Antinuclear Antibody-positive Patients With Non-small Cell Lung Cancer.","authors":"Akihiro Tsukaguchi, Akihiro Tamiya, Shoichi Fukuda, Yuki Iwahashi, Kensuke Kanaoka, Yuya Tanaka, Yuji Inagaki, Yoshihiko Taniguchi, Keiko Nakao, Tomoko Kagawa, Yoshinobu Matsuda, Kyoichi Okishio","doi":"10.21873/anticanres.17280","DOIUrl":"https://doi.org/10.21873/anticanres.17280","url":null,"abstract":"<p><strong>Background/aim: </strong>Pneumonitis during durvalumab consolidation therapy after chemoradiotherapy (CRT) is a major cause of treatment discontinuation. Although previous studies have revealed an association between antinuclear antibody (ANA) positivity and the safety and efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer (NSCLC), there are no reports on durvalumab consolidation therapy. This study investigated the safety and efficacy of durvalumab after CRT in ANA-positive patients.</p><p><strong>Patients and methods: </strong>We retrospectively reviewed patients with unresectable NSCLC treated with durvalumab after CRT between August 2018 and July 2022 at our institution. We evaluated the association among ANA positivity, treatment-related adverse events (AEs), and survival outcomes.</p><p><strong>Results: </strong>Overall, 80 patients were enrolled, 39 of whom were ANA-positive. Although there were no significant differences in the incidence of each AE of any grade, ANA-positive patients tended to have a higher frequency of pneumonitis of grade 3 to 5 than ANA-negative patients (12.8% vs. 2.4%, p=0.104). ANA-positive patients had a significantly shorter median progression-free survival (PFS) and overall survival (OS) than ANA-negative patients [14.9 months vs. not reached (NR), p=0.005; NR vs. NR, p=0.013]. Multivariate analysis revealed that ANA positivity was an independent predictor of shorter PFS (HR=2.23; 95% CI=1.16-4.29; p=0.016) and OS (HR=2.28; 95% CI=1.01-5.12; p=0.046).</p><p><strong>Conclusion: </strong>ANA-positive patients receiving durvalumab after CRT tended to have a higher frequency of severe pneumonitis and significantly worse PFS and OS compared with ANA-negative patients.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Changes in Bladder Volume During Radiotherapy for Prostate Cancer. 前列腺癌放疗期间膀胱容量的变化
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.21873/anticanres.17275
Dirk Rades, Florian Cremers, Christian Ziemann, Laura Splettstösser, Carlos A Narvaez-Wolf, Ahmed Al-Salool, Michael VON Staden, Jan-Dirk Küter, Stefan Janssen, Carmen Timke

Background/aim: Patients irradiated for prostate cancer may experience urinary toxicity, particularly if the bladder volume is small. A mobile application (app) that reminds the patients to drink water prior to each radiation fraction may help avoid small volumes. This study investigating bladder volumes during a radiotherapy course is a prerequisite for a prospective trial testing such a reminder app.

Patients and methods: Frequency of bladder volumes <200 ml and seven potential risk factors were retrospectively evaluated in 72 patients receiving external beam radiotherapy for non-metastatic prostate cancer.

Results: The mean and median values of the numbers of radiation fractions with bladder volumes <200 ml were 17.8 (standard deviation=12.0) and 16.5 (interquartile range Q1-Q3=7.5-29.5) fractions, respectively. Higher numbers of fractions with volumes <200 ml were significantly associated with pre-radiotherapy bladder volumes <200 ml (p<0.001) and high-risk prostate cancer (p=0.014).

Conclusion: The proportion of bladder volumes <200 ml during the radiotherapy course was high and needs to be decreased. Pre-radiotherapy bladder volume and risk level of prostate cancer were significant risk factors for higher numbers of fractions with volumes <200 ml. These results are important for designing a prospective trial.

背景/目的:接受前列腺癌照射的患者可能会出现泌尿系统毒性,尤其是在膀胱容量较小的情况下。提醒患者在每次放疗前喝水的移动应用程序(App)可能有助于避免尿量过少。这项调查放疗过程中膀胱容量的研究是测试此类提醒应用的前瞻性试验的前提条件:膀胱容量的频率 结果:有膀胱容量的放疗次数的平均值和中位值 结论:有膀胱容量的放疗次数比例较高:膀胱容量的比例
{"title":"Changes in Bladder Volume During Radiotherapy for Prostate Cancer.","authors":"Dirk Rades, Florian Cremers, Christian Ziemann, Laura Splettstösser, Carlos A Narvaez-Wolf, Ahmed Al-Salool, Michael VON Staden, Jan-Dirk Küter, Stefan Janssen, Carmen Timke","doi":"10.21873/anticanres.17275","DOIUrl":"https://doi.org/10.21873/anticanres.17275","url":null,"abstract":"<p><strong>Background/aim: </strong>Patients irradiated for prostate cancer may experience urinary toxicity, particularly if the bladder volume is small. A mobile application (app) that reminds the patients to drink water prior to each radiation fraction may help avoid small volumes. This study investigating bladder volumes during a radiotherapy course is a prerequisite for a prospective trial testing such a reminder app.</p><p><strong>Patients and methods: </strong>Frequency of bladder volumes <200 ml and seven potential risk factors were retrospectively evaluated in 72 patients receiving external beam radiotherapy for non-metastatic prostate cancer.</p><p><strong>Results: </strong>The mean and median values of the numbers of radiation fractions with bladder volumes <200 ml were 17.8 (standard deviation=12.0) and 16.5 (interquartile range Q1-Q3=7.5-29.5) fractions, respectively. Higher numbers of fractions with volumes <200 ml were significantly associated with pre-radiotherapy bladder volumes <200 ml (p<0.001) and high-risk prostate cancer (p=0.014).</p><p><strong>Conclusion: </strong>The proportion of bladder volumes <200 ml during the radiotherapy course was high and needs to be decreased. Pre-radiotherapy bladder volume and risk level of prostate cancer were significant risk factors for higher numbers of fractions with volumes <200 ml. These results are important for designing a prospective trial.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
True Benefits of Immune Checkpoint Inhibitors in the Treatment of Malignant Pleural Mesothelioma in Japan. 免疫检查点抑制剂在日本治疗恶性胸膜间皮瘤中的真正优势。
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.21873/anticanres.17244
Kozo Kuribayashi, Jun Hirano

In February 2004, the Food and Drug Administration (FDA) was the first to approve the combination of cisplatin (CDDP) and pemetrexed (PEM) as standard first-line chemotherapy for untreated, unresectable malignant pleural mesothelioma (MPM). However, after that approval, no progress was made in the standard first-line treatment of MPM for almost 15 years. Positive results from a phase 3 study (Mesothelioma Avastin Cisplatin Pemetrexed Study: MAPS) verifying the effect of bevacizumab, an anti-angiogenesis agent added to CDDP/PEM for unresectable MPM, were published in The Lancet in December 2015; however, this did not lead to approval by national drug regulatory agencies. Furthermore, no second-line treatment was established for cases refractory to CDDP/PEM. In August 2018, the Pharmaceuticals and Medical Devices Agency of Japan was the first in the world to approve monotherapy with nivolumab, an immune checkpoint inhibitor (ICI), for previously unresectable, advanced, or recurrent MPM. Following Japan, in October 2020, the FDA approved the combination of nivolumab and ipilimumab for the treatment of previously untreated, unresectable MPM. In this article, we review the transition of drug treatment for MPM, in light of the historical background, focusing on the benefits of ICIs.

2004 年 2 月,美国食品和药物管理局(FDA)率先批准将顺铂(CDDP)和培美曲塞(PEM)联合疗法作为标准一线化疗药物,用于治疗未经治疗、无法切除的恶性胸膜间皮瘤(MPM)。然而,在获得批准后的近 15 年里,MPM 的标准一线治疗一直没有取得进展。2015 年 12 月,《柳叶刀》杂志发表了一项 3 期研究(间皮瘤阿瓦斯汀-顺铂-培美曲塞研究:MAPS)的积极结果,验证了在 CDDP/PEM 中添加抗血管生成药物贝伐单抗治疗不可切除的 MPM 的效果;然而,这并没有促使国家药品监管机构批准该药物。此外,CDDP/PEM难治性病例的二线治疗尚未确立。2018 年 8 月,日本药品和医疗器械管理局在世界上率先批准使用免疫检查点抑制剂(ICI)nivolumab 单药治疗既往不可切除的晚期或复发性 MPM。继日本之后,美国食品和药物管理局于 2020 年 10 月批准了 nivolumab 和 ipilimumab 联合疗法,用于治疗既往未经治疗、无法切除的 MPM。在本文中,我们将结合历史背景回顾 MPM 药物治疗的转型,重点介绍 ICIs 的益处。
{"title":"True Benefits of Immune Checkpoint Inhibitors in the Treatment of Malignant Pleural Mesothelioma in Japan.","authors":"Kozo Kuribayashi, Jun Hirano","doi":"10.21873/anticanres.17244","DOIUrl":"https://doi.org/10.21873/anticanres.17244","url":null,"abstract":"<p><p>In February 2004, the Food and Drug Administration (FDA) was the first to approve the combination of cisplatin (CDDP) and pemetrexed (PEM) as standard first-line chemotherapy for untreated, unresectable malignant pleural mesothelioma (MPM). However, after that approval, no progress was made in the standard first-line treatment of MPM for almost 15 years. Positive results from a phase 3 study (Mesothelioma Avastin Cisplatin Pemetrexed Study: MAPS) verifying the effect of bevacizumab, an anti-angiogenesis agent added to CDDP/PEM for unresectable MPM, were published in The Lancet in December 2015; however, this did not lead to approval by national drug regulatory agencies. Furthermore, no second-line treatment was established for cases refractory to CDDP/PEM. In August 2018, the Pharmaceuticals and Medical Devices Agency of Japan was the first in the world to approve monotherapy with nivolumab, an immune checkpoint inhibitor (ICI), for previously unresectable, advanced, or recurrent MPM. Following Japan, in October 2020, the FDA approved the combination of nivolumab and ipilimumab for the treatment of previously untreated, unresectable MPM. In this article, we review the transition of drug treatment for MPM, in light of the historical background, focusing on the benefits of ICIs.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Therapeutic Responses to Two New SN-38 Derivatives in Colorectal Cancer Patient-Derived Xenografts and Respective 3D In Vitro Cultures. 结直肠癌患者衍生异种移植物和相应三维体外培养物对两种新型 SN-38 衍生物的治疗反应
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.21873/anticanres.17252
Katarzyna Unrug-Bielawska, David Earnshaw, Magdalena Cybulska-Lubak, Ewelina Kaniuga, Zuzanna Sandowska-Markiewicz, Malgorzata Statkiewicz, Izabela Rumienczyk, Michalina Dąbrowska, Justyna Kocik-Krol, Krzysztof Klimkiewicz, Magdalena Urbanowicz, Beata Naumczuk, Lech Kozerski, Marcin Krzykawski, Michal Mikula, Jerzy Ostrowski

Background/aim: SN-38, an active metabolite of irinotecan, exhibits toxicity to all proliferating cells, causing dose-limiting and potentially life-threatening side effects. Newly established water-soluble derivatives of SN-38, 7-ethyl-9-(N-morpholinyl)methyl-10-hydroxycamptothecin (BN-MOA) and 7-ethyl-9-(N-methylamino)methyl-10-hydroxycamptothecin (BN-NMe), exhibit a unique mechanism of spontaneous alkylation of aromatic bases in DNA and show greater in vitro activity on cancer cell lines than SN-38. The aim of this study was to compare the therapeutic responses to irinotecan, BN-MOA and BN-NMe in vivo and in vitro in 3D cultures using colorectal cancer (CRC) patient derived xenografts (PDX).

Materials and methods: Seven established PDX tissues were subcutaneously grown on the flanks of NSG or NSG-SGM3 mice and tumor diameters were measured with a caliper. Compounds were administrated intraperitoneally at 40 mg/kg every five days. 3D PDX cultures were performed on 96-well LifeGel plates and cell viability was determined with the CellTiter Glo 3D reagent.

Results: Treatment with irinotecan significantly delayed or stopped the growth of 5 out of 7 PDXs, with a greater level of inhibition from BN-MOA compared to irinotecan and BN-NMe. In vitro studies exhibited the same trends in SN-38 and BN-NMe but not in BN-MOA.

Conclusion: The new SN-38 derivatives, BN-MOA and BN-NMe, showed enhanced therapeutic effects compared to irinotecan in CRC models. BN-MOA demonstrated superior tumor inhibition in vivo, while BN-NMe had similar in vitro activity to SN-38. These findings highlight the potential of BN-MOA for greater antitumor efficacy in vivo, with BN-NMe showing comparable effectiveness to SN-38 in vitro. Future studies should optimize growth models to better predict anticancer drug responses.

背景/目的:SN-38 是伊立替康的一种活性代谢物,对所有增殖细胞都有毒性,会产生剂量限制性和可能危及生命的副作用。新发现的 SN-38 水溶性衍生物--7-乙基-9-(N-吗啉基)甲基-10-羟基喜树碱(BN-MOA)和 7-乙基-9-(N-甲基氨基)甲基-10-羟基喜树碱(BN-NMe)--表现出一种独特的 DNA 芳基自发烷基化机制,对癌细胞株的体外活性高于 SN-38。本研究的目的是比较伊立替康、BN-MOA 和 BN-NMe 对结肠直肠癌(CRC)患者衍生异种移植物(PDX)的体内和体外三维培养的治疗反应:在 NSG 或 NSG-SGM3 小鼠腹部皮下注射七种已建立的 PDX 组织,并用卡尺测量肿瘤直径。每五天腹腔注射一次化合物,剂量为 40 毫克/千克。在 96 孔 LifeGel 板上进行三维 PDX 培养,用 CellTiter Glo 3D 试剂测定细胞存活率:结果:伊立替康治疗可明显延缓或阻止 7 个 PDX 中 5 个的生长,与伊立替康和 BN-NMe 相比,BN-MOA 的抑制程度更高。体外研究显示,SN-38 和 BN-NMe 具有相同的趋势,而 BN-MOA 则没有:结论:与伊立替康相比,新型 SN-38 衍生物 BN-MOA 和 BN-NMe 在 CRC 模型中显示出更强的治疗效果。BN-MOA 对体内肿瘤的抑制作用更强,而 BN-NMe 的体外活性与 SN-38 相似。这些发现凸显了 BN-MOA 在体内发挥更大抗肿瘤疗效的潜力,而 BN-NMe 在体外的疗效与 SN-38 不相上下。未来的研究应优化生长模型,以更好地预测抗癌药物的反应。
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引用次数: 0
Predictive Biomarkers of Lymph Node Metastasis in Early Gastric Cancer: A Reference of Clinicopathological Characteristics, Protein Expression, Epstein-Barr Virus Status, and Microsatellite Instability. 早期胃癌淋巴结转移的预测性生物标志物:临床病理特征、蛋白表达、Epstein-Barr 病毒状态和微卫星不稳定性的参考文献
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.21873/anticanres.17273
Sun-Ju Byeon, Mee Soo Chang, Hye Eun Park, Doehee Kang, Yuting Wang, Dong-Seok Han, Hye Sung Ahn, Seung Chul Heo, Myong Seok Lee, Won Kim, Su Hwan Kim, Dong-Won Ahn, Kook Lae Lee

Background/aim: Predicting lymph node metastasis (LNM) in early gastric cancer (EGC) is crucial for making treatment decisions. This study aimed to confirm risk factors for LNM and identify novel auxiliary biomarkers for predicting LNM in EGC.

Patients and methods: We established a training set, comprising 63 patients with LNM-EGC and 274 patients with non-LNM EGC, and a test set, comprising 19 patients with LNM-EGC and 146 non-LNM EGC. Immunohistochemistry for lymphangiogenic and related pathway components (VEGF-C, TGF-β1, SMAD2/3, VEGF-D, pSTAT3, E-cadherin, CD44, c-MET, YAP, and HER2), in situ hybridization for Epstein-Barr virus-encoded small RNAs, and multiplex PCR for microsatellite instability were conducted.

Results: In the training set, Lauren's diffuse/mixed classification, stromal desmoplasia, submucosal invasion ≥500 μm, lymphatic invasion, and high VEGF-C and SMAD2/3 expression were independent risk factors for LNM (p<0.05). A large tumor size, mixed histology, submucosal invasion, perineural invasion, and ulceration were determined as risk factors using univariate analysis (p<0.05). The tumor cutoff size for predicting LNM was 2.65 cm, based on a ROC analysis. The test set study verified that stromal desmoplasia, submucosal invasion, and high VEGF-C expression were independent risk factors for LNM (p<0.05). Moreover, mixed histology, lymphatic invasion, ulceration, and high SMAD 2/3 expression were identified as additional risk factors using univariate analysis (p<0.05).

Conclusion: Stromal desmoplasia, submucosal invasion, and high VEGF-C expression are potential biomarkers for LNM in EGC. VEGF-C expression might serve as an adjunct biomarker for predicting LNM on forceps-biopsy tissue at initial diagnosis.

背景/目的:预测早期胃癌(EGC)的淋巴结转移(LNM)对治疗决策至关重要。本研究旨在确认淋巴结转移的风险因素,并确定预测EGC淋巴结转移的新型辅助生物标志物:我们建立了一个训练集,其中包括 63 名 LNM-EGC 患者和 274 名非 LNM EGC 患者;还建立了一个测试集,其中包括 19 名 LNM-EGC 患者和 146 名非 LNM EGC 患者。对淋巴管生成和相关通路成分(VEGF-C、TGF-β1、SMAD2/3、VEGF-D、pSTAT3、E-cadherin、CD44、c-MET、YAP和HER2)进行了免疫组化,对Epstein-Barr病毒编码的小RNA进行了原位杂交,并对微卫星不稳定性进行了多重PCR检测:结果:在训练集中,劳伦的弥漫/混合分类、基质脱落、粘膜下浸润≥500 μm、淋巴浸润、VEGF-C和SMAD2/3高表达是LNM的独立危险因素(p结论:基质脱落、粘膜下浸润≥500 μm、淋巴浸润、VEGF-C和SMAD2/3高表达是LNM的独立危险因素:基质脱落、粘膜下侵袭和 VEGF-C 高表达是 EGC LNM 的潜在生物标志物。VEGF-C的表达可作为辅助生物标志物,用于预测初诊时钳取活检组织中的LNM。
{"title":"Predictive Biomarkers of Lymph Node Metastasis in Early Gastric Cancer: A Reference of Clinicopathological Characteristics, Protein Expression, Epstein-Barr Virus Status, and Microsatellite Instability.","authors":"Sun-Ju Byeon, Mee Soo Chang, Hye Eun Park, Doehee Kang, Yuting Wang, Dong-Seok Han, Hye Sung Ahn, Seung Chul Heo, Myong Seok Lee, Won Kim, Su Hwan Kim, Dong-Won Ahn, Kook Lae Lee","doi":"10.21873/anticanres.17273","DOIUrl":"https://doi.org/10.21873/anticanres.17273","url":null,"abstract":"<p><strong>Background/aim: </strong>Predicting lymph node metastasis (LNM) in early gastric cancer (EGC) is crucial for making treatment decisions. This study aimed to confirm risk factors for LNM and identify novel auxiliary biomarkers for predicting LNM in EGC.</p><p><strong>Patients and methods: </strong>We established a training set, comprising 63 patients with LNM-EGC and 274 patients with non-LNM EGC, and a test set, comprising 19 patients with LNM-EGC and 146 non-LNM EGC. Immunohistochemistry for lymphangiogenic and related pathway components (VEGF-C, TGF-β1, SMAD2/3, VEGF-D, pSTAT3, E-cadherin, CD44, c-MET, YAP, and HER2), in situ hybridization for Epstein-Barr virus-encoded small RNAs, and multiplex PCR for microsatellite instability were conducted.</p><p><strong>Results: </strong>In the training set, Lauren's diffuse/mixed classification, stromal desmoplasia, submucosal invasion ≥500 μm, lymphatic invasion, and high VEGF-C and SMAD2/3 expression were independent risk factors for LNM (p<0.05). A large tumor size, mixed histology, submucosal invasion, perineural invasion, and ulceration were determined as risk factors using univariate analysis (p<0.05). The tumor cutoff size for predicting LNM was 2.65 cm, based on a ROC analysis. The test set study verified that stromal desmoplasia, submucosal invasion, and high VEGF-C expression were independent risk factors for LNM (p<0.05). Moreover, mixed histology, lymphatic invasion, ulceration, and high SMAD 2/3 expression were identified as additional risk factors using univariate analysis (p<0.05).</p><p><strong>Conclusion: </strong>Stromal desmoplasia, submucosal invasion, and high VEGF-C expression are potential biomarkers for LNM in EGC. VEGF-C expression might serve as an adjunct biomarker for predicting LNM on forceps-biopsy tissue at initial diagnosis.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Intraoperative Bleeding Complications Leading to Blood Transfusions (BloTs) in 17,412 Cholecystectomies in Finland: A Study With Special Reference to Elderly Patients. 芬兰 17,412 例胆囊切除术中导致输血的术中出血并发症 (BloTs):一项特别针对老年患者的研究。
IF 1.6 4区 医学 Q4 ONCOLOGY Pub Date : 2024-10-01 DOI: 10.21873/anticanres.17274
Antti Kivivuori, Pekka Lammi, Matti Eskelinen, Tuomo Rantanen, Hannu Paajanen, Jukka Pulkkinen, Mika Ukkonen

Background/aim: Cholelithiasis (Chole) is one of the most common diseases needing operative management worldwide. However, there are few studies assessing the intraoperative bleeding (IOB) complications leading to blood transfusions (BloTs) in elderly patients with cholecystectomy (Ccy).

Patients and methods: Outcome after IOB complications and need for BloTs in a cohort of 17,412 patients with Ccys were assessed with special reference to elderly Ccy patients.

Results: A total of 17,412 patients underwent Ccy and 11% of Ccy patients (1,856/17,412) were aged ≥75 years. The Ccy patients ≥75 years underwent more often emergency/open Ccys. Red blood cell BloTs were administered five times more often to Ccy patients ≥75 years versus Ccy patients <75 years (13% versus 2.6%, p<0.001). In Ccys by emergency surgery indications, the need for BloTs was four times higher in Ccy patients ≥75 years versus Ccy patients <75 years (5.5% versus 1.3%, p<0.001).

Conclusion: The elderly Chole patients have a higher risk than younger Chole patients for perioperative IOB complications and thus are more likely to need BloTs.

背景/目的:胆石症(Chole)是全世界需要手术治疗的最常见疾病之一。然而,很少有研究评估老年胆囊切除术(Ccy)患者术中出血(IOB)并发症导致输血(BloTs)的情况:患者和方法:对17,412名胆囊切除术患者术中出血并发症后的结果和输血需求进行评估,特别是老年胆囊切除术患者:共有 17,412 名患者接受了 Ccy,其中 11% 的 Ccy 患者(1,856/17,412)年龄≥75 岁。年龄≥75 岁的 Ccy 患者更多地接受急诊/开放式 Ccy。结论:老年胆囊癌患者发生围手术期 IOB 并发症的风险高于年轻胆囊癌患者,因此更有可能需要 BloTs。
{"title":"Intraoperative Bleeding Complications Leading to Blood Transfusions (BloTs) in 17,412 Cholecystectomies in Finland: A Study With Special Reference to Elderly Patients.","authors":"Antti Kivivuori, Pekka Lammi, Matti Eskelinen, Tuomo Rantanen, Hannu Paajanen, Jukka Pulkkinen, Mika Ukkonen","doi":"10.21873/anticanres.17274","DOIUrl":"https://doi.org/10.21873/anticanres.17274","url":null,"abstract":"<p><strong>Background/aim: </strong>Cholelithiasis (Chole) is one of the most common diseases needing operative management worldwide. However, there are few studies assessing the intraoperative bleeding (IOB) complications leading to blood transfusions (BloTs) in elderly patients with cholecystectomy (Ccy).</p><p><strong>Patients and methods: </strong>Outcome after IOB complications and need for BloTs in a cohort of 17,412 patients with Ccys were assessed with special reference to elderly Ccy patients.</p><p><strong>Results: </strong>A total of 17,412 patients underwent Ccy and 11% of Ccy patients (1,856/17,412) were aged ≥75 years. The Ccy patients ≥75 years underwent more often emergency/open Ccys. Red blood cell BloTs were administered five times more often to Ccy patients ≥75 years versus Ccy patients <75 years (13% versus 2.6%, p<0.001). In Ccys by emergency surgery indications, the need for BloTs was four times higher in Ccy patients ≥75 years versus Ccy patients <75 years (5.5% versus 1.3%, p<0.001).</p><p><strong>Conclusion: </strong>The elderly Chole patients have a higher risk than younger Chole patients for perioperative IOB complications and thus are more likely to need BloTs.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Anticancer research
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