Cancer Medicine最新文献_第6页

Screening for Hepatocellular Carcinoma Recurrence After Liver Transplantation: Prospective Validation of Binary Criteria 肝移植后肝癌复发的筛查：二元标准的前瞻性验证

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-11-29 DOI: 10.1002/cam4.71428

Wesley Dixon, Shaun Chandna, Jordan S. Sack, Meagan Gray, Christina N. Brown, Sampath Poreddy, Kai Ha, Michael R. Schoech, Stephen D. Zucker

Background

Many centers screen all recipients for hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). This approach may add substantial burdens of cost, incidental findings, and, depending on the imaging modality, radiation and/or contrast-induced complications. We created simple criteria to help clinicians identify low-risk patients in whom post-LT surveillance offers marginal utility.

Methods

Criteria were developed retrospectively using adults with HCC who underwent LT at the University of Cincinnati from 2000 to 2014. Low-risk patients had none of the following at LT: (1) outside Milan criteria, (2) alpha-fetoprotein ≥ 200 ng/mL, (3) prior hepatectomy with vascular invasion or unknown histology, and (4) any vascular invasion or > 3 lesions on explant, or extrahepatic extension noted intraoperatively. Criteria were retrospectively validated in adults transplanted for HCC at Mass General Brigham from 2015 to 2023 and prospectively assessed at Cincinnati where low-risk patients received no post-LT surveillance.

Results

Among 132 development cohort patients, 14 (10.6%) developed recurrent HCC at a median of 2.0 (range 0.1–9.7) years. Only 1 (1.1%) of the 91 (68.9%) patients deemed low-risk by the proposed criteria developed recurrence compared to 13 (31.7%) of the high-risk patients (p < 0.001). In the validation cohort (n = 188), recurrence occurred in 1 (0.9%) of 114 (60.6%) low-risk and 16 (21.6%) high-risk patients. In the prospective cohort (n = 55), none of 42 (76.4%) low-risk patients developed recurrence versus 3 (23.1%) high-risk patients (p = 0.011) after 8.0 (0.1–9.4) years of follow-up. The criteria performed similarly to the RETREAT score 0 across cohorts (n = 375) in identifying patients without recurrence as low-risk (negative predictive value 99.2% vs. 97.1%) but required screening significantly fewer patients (34.1% vs. 81.9%).

Conclusions

These prospectively validated criteria offer clinicians a practical tool for easily and accurately determining which patients would benefit from surveillance for HCC recurrence after LT. Surveillance targeting only high-risk patients could reduce the harms of excess screening.

背景：许多中心对肝移植（LT）后所有受者进行肝细胞癌（HCC）复发筛查。这种方法可能会增加大量的费用负担、意外发现，并且根据成像方式，可能会出现辐射和/或造影剂引起的并发症。我们创建了简单的标准来帮助临床医生识别低风险患者，在这些患者中，肝移植后监测具有边际效用。方法回顾性研究2000年至2014年在辛辛那提大学接受肝移植的成年HCC患者的标准。低风险患者在肝移植时无以下情况：(1)超出米兰标准，(2)甲胎蛋白≥200 ng/mL，(3)既往肝切除术伴血管侵犯或组织学未知，(4)任何血管侵犯或术中发现外植体病变，或肝外延伸。2015年至2023年，在麻省总医院布里格姆进行HCC移植的成人标准回顾性验证，并在辛辛那提进行前瞻性评估，其中低风险患者未接受肝移植后监测。结果在132例发展队列患者中，14例（10.6%）在中位2.0年（0.1-9.7年）发生复发性HCC。在91例（68.9%）低危患者中，只有1例（1.1%）复发，而高危患者中有13例（31.7%）复发（p < 0.001）。在验证队列（n = 188）中，114例（60.6%）低危患者中有1例（0.9%）复发，16例（21.6%）高危患者复发。在前瞻性队列（n = 55）中，随访8.0年（0.1-9.4）后，42例（76.4%）低危患者无复发，3例（23.1%）高危患者无复发（p = 0.011）。在所有队列（n = 375）中，该标准在确定无复发患者为低风险（阴性预测值99.2%对97.1%）方面的表现与RETREAT评分0相似，但需要筛查的患者明显减少（34.1%对81.9%）。这些前瞻性验证的标准为临床医生提供了一种实用的工具，可以轻松准确地确定哪些患者将受益于肝移植后HCC复发的监测。仅针对高危患者的监测可以减少过度筛查的危害。

{"title":"Screening for Hepatocellular Carcinoma Recurrence After Liver Transplantation: Prospective Validation of Binary Criteria","authors":"Wesley Dixon, Shaun Chandna, Jordan S. Sack, Meagan Gray, Christina N. Brown, Sampath Poreddy, Kai Ha, Michael R. Schoech, Stephen D. Zucker","doi":"10.1002/cam4.71428","DOIUrl":"https://doi.org/10.1002/cam4.71428","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Many centers screen all recipients for hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). This approach may add substantial burdens of cost, incidental findings, and, depending on the imaging modality, radiation and/or contrast-induced complications. We created simple criteria to help clinicians identify low-risk patients in whom post-LT surveillance offers marginal utility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Criteria were developed retrospectively using adults with HCC who underwent LT at the University of Cincinnati from 2000 to 2014. Low-risk patients had none of the following at LT: (1) outside Milan criteria, (2) alpha-fetoprotein ≥ 200 ng/mL, (3) prior hepatectomy with vascular invasion or unknown histology, and (4) any vascular invasion or > 3 lesions on explant, or extrahepatic extension noted intraoperatively. Criteria were retrospectively validated in adults transplanted for HCC at Mass General Brigham from 2015 to 2023 and prospectively assessed at Cincinnati where low-risk patients received no post-LT surveillance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 132 development cohort patients, 14 (10.6%) developed recurrent HCC at a median of 2.0 (range 0.1–9.7) years. Only 1 (1.1%) of the 91 (68.9%) patients deemed low-risk by the proposed criteria developed recurrence compared to 13 (31.7%) of the high-risk patients (<i>p</i> < 0.001). In the validation cohort (<i>n</i> = 188), recurrence occurred in 1 (0.9%) of 114 (60.6%) low-risk and 16 (21.6%) high-risk patients. In the prospective cohort (<i>n</i> = 55), none of 42 (76.4%) low-risk patients developed recurrence versus 3 (23.1%) high-risk patients (<i>p</i> = 0.011) after 8.0 (0.1–9.4) years of follow-up. The criteria performed similarly to the RETREAT score 0 across cohorts (<i>n</i> = 375) in identifying patients without recurrence as low-risk (negative predictive value 99.2% vs. 97.1%) but required screening significantly fewer patients (34.1% vs. 81.9%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These prospectively validated criteria offer clinicians a practical tool for easily and accurately determining which patients would benefit from surveillance for HCC recurrence after LT. Surveillance targeting only high-risk patients could reduce the harms of excess screening.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 23","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71428","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626550","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

Fertility Concerns and Outcomes Among Adolescent and Young Adult Males With Melanoma Receiving Immunotherapy: A Mixed-Methods Study 青少年和年轻成年男性黑色素瘤患者接受免疫治疗的生育问题和结果：一项混合方法研究

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-11-29 DOI: 10.1002/cam4.71437

Haadi Ali, Ellen Wold, Tarek Haykal, Peter Dawood, Victoria Wytiaz

Introduction

Immune checkpoint inhibitors (ICIs) are often the initial treatment choice for melanoma, the third most common cancer in the adolescent and young adult (AYA) male population. Although ICIs have improved survival rates, their effects on male fertility and the adequacy of related counseling remain unclear. This study aimed to both characterize the current state of fertility discussions in male AYA patients with melanoma receiving first-line ICIs and to explore their experiences and concerns regarding reproductive health.

Methods

We conducted a mixed-methods study of 38 male patients aged 18–39 with metastatic or locally advanced melanoma treated with first-line PD-1/PD-L1/CTLA-4 therapies at a single academic center between 2013 and 2024. Quantitative medical record review assessed fertility counseling and preservation actions. Semi-structured interviews were conducted with ten living patients from this cohort to explore knowledge, concerns, and experiences surrounding fertility and reproductive health. Thematic analysis identified key patient perspectives.

Results

Among 38 patients (median age 32), 71% had stage IV disease and received combination immunotherapy. 74% of patients experienced at least one immune-related adverse event (irAE). Fertility counseling was documented for 27 patients, with eight referred for fertility preservation. Of the ten interviewees, nine recalled discussing fertility, while only three pursued preservation. Qualitative themes included challenges accepting uncertainty about family planning, pressure to accelerate planning, feelings of forced maturity, difficulty processing complex information, and concerns about the reliability of information from family, providers, and social media.

Conclusion

Although most young males with advanced melanoma treated with first-line ICIs had documented fertility discussions, few elected fertility preservation. Patient experiences highlight the need for collaboration among oncologists, fertility specialists, and supportive professionals to develop tailored counseling and educational materials for male AYA patients with advanced melanoma.

免疫检查点抑制剂（ICIs）通常是黑色素瘤的初始治疗选择，黑色素瘤是青少年和年轻成人（AYA）男性人群中第三大常见癌症。虽然ICIs提高了生存率，但其对男性生育能力的影响和相关咨询的充分性仍不清楚。本研究旨在描述接受一线ICIs治疗的男性AYA黑色素瘤患者生育讨论的现状，并探讨他们在生殖健康方面的经历和担忧。2013年至2024年，我们在一个学术中心对38名年龄在18-39岁的转移性或局部晚期黑色素瘤患者进行了一项混合方法研究，这些患者接受了一线PD-1/PD-L1/CTLA-4治疗。定量医疗记录审查评估生育咨询和保存行动。对来自该队列的10名在世患者进行了半结构化访谈，以探索有关生育和生殖健康的知识、关注和经验。专题分析确定了关键的患者观点。结果38例患者（中位年龄32岁）中，71%为IV期，接受了联合免疫治疗。74%的患者经历了至少一次免疫相关不良事件（irAE）。记录了27例患者的生育咨询，其中8例为生育保留。在10位受访者中，有9位回忆起讨论过生育问题，而只有3位追求保护。定性主题包括接受计划生育不确定性的挑战、加速计划的压力、被迫成熟的感觉、处理复杂信息的困难，以及对来自家庭、提供者和社交媒体的信息可靠性的担忧。结论：虽然大多数接受一线ICIs治疗的晚期黑色素瘤年轻男性有生育讨论记录，但很少有人选择保留生育能力。患者的经验强调了肿瘤学家、生育专家和支持性专业人员之间合作的必要性，以开发针对晚期黑色素瘤男性AYA患者的量身定制的咨询和教育材料。

{"title":"Fertility Concerns and Outcomes Among Adolescent and Young Adult Males With Melanoma Receiving Immunotherapy: A Mixed-Methods Study","authors":"Haadi Ali, Ellen Wold, Tarek Haykal, Peter Dawood, Victoria Wytiaz","doi":"10.1002/cam4.71437","DOIUrl":"https://doi.org/10.1002/cam4.71437","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Immune checkpoint inhibitors (ICIs) are often the initial treatment choice for melanoma, the third most common cancer in the adolescent and young adult (AYA) male population. Although ICIs have improved survival rates, their effects on male fertility and the adequacy of related counseling remain unclear. This study aimed to both characterize the current state of fertility discussions in male AYA patients with melanoma receiving first-line ICIs and to explore their experiences and concerns regarding reproductive health.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a mixed-methods study of 38 male patients aged 18–39 with metastatic or locally advanced melanoma treated with first-line PD-1/PD-L1/CTLA-4 therapies at a single academic center between 2013 and 2024. Quantitative medical record review assessed fertility counseling and preservation actions. Semi-structured interviews were conducted with ten living patients from this cohort to explore knowledge, concerns, and experiences surrounding fertility and reproductive health. Thematic analysis identified key patient perspectives.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 38 patients (median age 32), 71% had stage IV disease and received combination immunotherapy. 74% of patients experienced at least one immune-related adverse event (irAE). Fertility counseling was documented for 27 patients, with eight referred for fertility preservation. Of the ten interviewees, nine recalled discussing fertility, while only three pursued preservation. Qualitative themes included challenges accepting uncertainty about family planning, pressure to accelerate planning, feelings of forced maturity, difficulty processing complex information, and concerns about the reliability of information from family, providers, and social media.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although most young males with advanced melanoma treated with first-line ICIs had documented fertility discussions, few elected fertility preservation. Patient experiences highlight the need for collaboration among oncologists, fertility specialists, and supportive professionals to develop tailored counseling and educational materials for male AYA patients with advanced melanoma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 23","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71437","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626551","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

Maritoclax Overcomes FBW7 Deficiency-Driven Irinotecan Resistance in Colorectal Cancer by Targeting MCL1 Maritoclax通过靶向MCL1克服FBW7缺陷驱动的结直肠癌伊立替康耐药

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-11-28 DOI: 10.1002/cam4.71419

Qian Lin, Shuting Liu, Hongfei Jiang, Shasha Wang, Yixin Duan

Introduction

FBW7, a tumor suppressive E3 ubiquitin ligase frequently mutated in colorectal cancer (CRC), mediates chemotherapy resistance. While irinotecan (via its active metabolite SN38) is a first-line TOP1 inhibitor for advanced CRC, the mechanistic link between FBW7 dysfunction and irinotecan resistance remains elusive.

Methods

CRISPR/Cas9 gene editing and RNA interference were applied to establish FBW7-knockout and -knockdown CRC cells. CCK8 assay was performed to detect the inhibition ratio of SN38 and Maritoclax on CRC cells. Western blot, immunochemistry, RT-qPCR and co-immunoprecipitation were performed to detect the expression and interaction of FBW7 and MCL1. The conformational change of the FBW7 R465C mutation and its interaction with substrates were elucidated through AlphaFold. An animal experiment was performed to detect the in vivo therapeutic effect of irinotecan and Maritoclax.

Results

FBW7 deficiency (including loss, low expression and mutation) reduced SN38 sensitivity and upregulated MCL1 expression in both CRC cells and patient tissues. The R465C mutation disrupted FBW7-MCL1 binding and stabilized MCL1. Moreover, SN38 modulated MCL1 expression, elevated MCL1 expression led to SN38 resistance in CRC cells. Maritoclax, a specific MCL1 inhibitor, reversed irinotecan/SN38 resistance in FBW7-deficient CRC cells and xenograft models, synergizing with irinotecan to suppress tumor growth.

Conclusions

FBW7 deficiency induces irinotecan resistance via MCL1 stabilization, which is therapeutically exploitable by Maritoclax. Our work identifies MCL1 inhibition as a precision strategy for FBW7-deficient CRC and supports clinical translation of Maritoclax-irinotecan combinations.

FBW7是一种肿瘤抑制E3泛素连接酶，在结直肠癌（CRC）中经常突变，介导化疗耐药。虽然伊立替康（通过其活性代谢物SN38）是晚期结直肠癌的一线TOP1抑制剂，但FBW7功能障碍与伊立替康耐药之间的机制联系尚不明确。方法采用CRISPR/Cas9基因编辑和RNA干扰技术，建立fbw7敲除和敲低CRC细胞。CCK8法检测SN38和Maritoclax对CRC细胞的抑制率。Western blot、免疫化学、RT-qPCR、共免疫沉淀检测FBW7与MCL1的表达及相互作用。通过AlphaFold分析了FBW7 R465C突变的构象变化及其与底物的相互作用。采用动物实验检测伊立替康和马里托克的体内治疗效果。结果FBW7缺失（包括缺失、低表达和突变）降低了CRC细胞和患者组织中SN38的敏感性，上调了MCL1的表达。R465C突变破坏了FBW7-MCL1的结合，稳定了MCL1。此外，SN38调节MCL1表达，MCL1表达升高导致CRC细胞中SN38耐药。特异性MCL1抑制剂Maritoclax在fbw7缺陷CRC细胞和异种移植模型中逆转伊立替康/SN38耐药，与伊立替康协同抑制肿瘤生长。结论FBW7缺乏通过mcl - 1稳定诱导伊立替康耐药，可用于马里托克的治疗。我们的工作确定MCL1抑制是fbw7缺陷CRC的精确策略，并支持马里托克-伊立替康联合治疗的临床翻译。

{"title":"Maritoclax Overcomes FBW7 Deficiency-Driven Irinotecan Resistance in Colorectal Cancer by Targeting MCL1","authors":"Qian Lin, Shuting Liu, Hongfei Jiang, Shasha Wang, Yixin Duan","doi":"10.1002/cam4.71419","DOIUrl":"https://doi.org/10.1002/cam4.71419","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>FBW7, a tumor suppressive E3 ubiquitin ligase frequently mutated in colorectal cancer (CRC), mediates chemotherapy resistance. While irinotecan (via its active metabolite SN38) is a first-line TOP1 inhibitor for advanced CRC, the mechanistic link between FBW7 dysfunction and irinotecan resistance remains elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CRISPR/Cas9 gene editing and RNA interference were applied to establish FBW7-knockout and -knockdown CRC cells. CCK8 assay was performed to detect the inhibition ratio of SN38 and Maritoclax on CRC cells. Western blot, immunochemistry, RT-qPCR and co-immunoprecipitation were performed to detect the expression and interaction of FBW7 and MCL1. The conformational change of the FBW7 R465C mutation and its interaction with substrates were elucidated through AlphaFold. An animal experiment was performed to detect the in vivo therapeutic effect of irinotecan and Maritoclax.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>FBW7 deficiency (including loss, low expression and mutation) reduced SN38 sensitivity and upregulated MCL1 expression in both CRC cells and patient tissues. The R465C mutation disrupted FBW7-MCL1 binding and stabilized MCL1. Moreover, SN38 modulated MCL1 expression, elevated MCL1 expression led to SN38 resistance in CRC cells. Maritoclax, a specific MCL1 inhibitor, reversed irinotecan/SN38 resistance in FBW7-deficient CRC cells and xenograft models, synergizing with irinotecan to suppress tumor growth.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>FBW7 deficiency induces irinotecan resistance via MCL1 stabilization, which is therapeutically exploitable by Maritoclax. Our work identifies MCL1 inhibition as a precision strategy for FBW7-deficient CRC and supports clinical translation of Maritoclax-irinotecan combinations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 23","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71419","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626227","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

METTL14 Regulates the Expression of Genes Related to Interferon, Interleukin and MHC Class I in Nasopharyngeal Carcinoma Cells METTL14调控鼻咽癌细胞中干扰素、白细胞介素和MHC I类相关基因的表达

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-11-28 DOI: 10.1002/cam4.71371

Zhihao Zhou, Jing Wang, Lingjun Shen, Liuxin Han, Qiwen Li, Aibing Wu, Jing Li, Zuming Liang, Litong Zhu, Danhua He, Ying Zhou, Shihao Huang, Zhanlin Zhao, Jinge Cong, Zhitao Peng, Ping Zhao, Shuna Ye, Binyi Bai, Xuanjia Hong, Guanqi Dai, Ye Lei, Wentao Zhao, Junshuang Jia, Xiaolin Lin, Dong Xiao, Yuqin Zhang, Taoyan Lin

Background

Nasopharyngeal carcinoma (NPC), highly prevalent in southern China, often leads to treatment failure in advanced stages due to recurrence or metastasis. While METTL14 plays a crucial role in cancer, its regulation of immune- and inflammation-related genes remains poorly understood. This study aims to investigate whether METTL14 is involved in regulating the expression of genes associated with tumor necrosis factor (TNF), interferon (IFN), interleukin (IL), and MHC class I in NPC cells.

Methods

Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to examine METTL14 expression in NPC cells with either shMETTL14 knockdown or METTL14 overexpression. RNA sequencing was performed to identify differentially expressed genes associated with TNF, IFN, IL, and MHC class I in NPC cells, and qRT-PCR was used to validate the expression of these genes. A cytokine production assay was conducted to measure the levels of TNFSF9, IFI16, IL-6, IL-7, CXCL10, and HLA-B.

Results

Our study demonstrates that METTL14 potentially plays a fundamental role in modulating the expression of genes associated with TNF, IFN, IL, and MHC class I in NPC cells. RNA sequencing of NPC cells showed that METTL14 upregulated or downregulated several genes associated with immunity and inflammation, including TNF, IFN, IL, and MHC class I. RNA interference-mediated knockdown of METTL14 revealed its regulatory effects on TNF-related genes (e.g., TNFRSF12A, TNFRSF9, TNFSF15), IFN-induced genes (e.g., PSMC6, PSMD1, PSMA2, PSMA3, PSMB2), and IL-related genes (e.g., CCL5, IL1B, IL32, IL7R, IL6, IL7, CXCL2). Furthermore, METTL14 was found to positively regulate MHC class I gene expression (e.g., HLA-A, -B, -C, -E, -F) in NPC cells.

Conclusions

These findings demonstrate, for the first time, that METTL14 modulates the expression of genes related to TNF, IFN, IL, and MHC class I in NPC, proposing a novel role for METTL14 in linking inflammation with cancer, a function that has not been fully elucidated.

背景：鼻咽癌（NPC）在中国南方地区高发，常因复发或转移导致晚期治疗失败。虽然METTL14在癌症中起着至关重要的作用，但其对免疫和炎症相关基因的调节仍知之甚少。本研究旨在探讨METTL14是否参与调节鼻咽癌细胞中肿瘤坏死因子（TNF）、干扰素（IFN）、白细胞介素（IL）和MHC I类相关基因的表达。方法采用实时荧光定量聚合酶链反应（qRT-PCR）和免疫印迹法检测METTL14在鼻咽癌细胞中低表达和过表达的表达情况。通过RNA测序鉴定鼻咽癌细胞中与TNF、IFN、IL和MHC I类相关的差异表达基因，并使用qRT-PCR验证这些基因的表达。通过细胞因子产生测定测定TNFSF9、IFI16、IL-6、IL-7、CXCL10和HLA-B的水平。我们的研究表明，METTL14可能在鼻咽癌细胞中调节TNF、IFN、IL和MHC I类相关基因的表达中起着重要作用。鼻鼻癌细胞的RNA测序显示，METTL14上调或下调了几种与免疫和炎症相关的基因，包括TNF、IFN、IL和MHC i类。RNA干扰介导的METTL14敲低揭示了其对TNF相关基因（如TNFRSF12A、TNFRSF9、TNFSF15）、IFN诱导基因（如PSMC6、PSMD1、PSMA2、PSMA3、PSMB2）和IL相关基因（如CCL5、IL1B、IL32、IL7R、IL6、IL7、CXCL2）的调节作用。此外，METTL14在鼻咽癌细胞中正调控MHC I类基因（如HLA-A、-B、-C、-E、-F）的表达。这些发现首次表明，METTL14调节鼻咽癌中与TNF、IFN、IL和MHC I类相关基因的表达，提出了METTL14在炎症与癌症之间的联系中的新作用，该功能尚未完全阐明。

{"title":"METTL14 Regulates the Expression of Genes Related to Interferon, Interleukin and MHC Class I in Nasopharyngeal Carcinoma Cells","authors":"Zhihao Zhou, Jing Wang, Lingjun Shen, Liuxin Han, Qiwen Li, Aibing Wu, Jing Li, Zuming Liang, Litong Zhu, Danhua He, Ying Zhou, Shihao Huang, Zhanlin Zhao, Jinge Cong, Zhitao Peng, Ping Zhao, Shuna Ye, Binyi Bai, Xuanjia Hong, Guanqi Dai, Ye Lei, Wentao Zhao, Junshuang Jia, Xiaolin Lin, Dong Xiao, Yuqin Zhang, Taoyan Lin","doi":"10.1002/cam4.71371","DOIUrl":"https://doi.org/10.1002/cam4.71371","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nasopharyngeal carcinoma (NPC), highly prevalent in southern China, often leads to treatment failure in advanced stages due to recurrence or metastasis. While METTL14 plays a crucial role in cancer, its regulation of immune- and inflammation-related genes remains poorly understood. This study aims to investigate whether METTL14 is involved in regulating the expression of genes associated with tumor necrosis factor (TNF), interferon (IFN), interleukin (IL), and MHC class I in NPC cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to examine METTL14 expression in NPC cells with either shMETTL14 knockdown or METTL14 overexpression. RNA sequencing was performed to identify differentially expressed genes associated with TNF, IFN, IL, and MHC class I in NPC cells, and qRT-PCR was used to validate the expression of these genes. A cytokine production assay was conducted to measure the levels of TNFSF9, IFI16, IL-6, IL-7, CXCL10, and HLA-B.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our study demonstrates that METTL14 potentially plays a fundamental role in modulating the expression of genes associated with TNF, IFN, IL, and MHC class I in NPC cells. RNA sequencing of NPC cells showed that METTL14 upregulated or downregulated several genes associated with immunity and inflammation, including TNF, IFN, IL, and MHC class I. RNA interference-mediated knockdown of METTL14 revealed its regulatory effects on TNF-related genes (e.g., TNFRSF12A, TNFRSF9, TNFSF15), IFN-induced genes (e.g., PSMC6, PSMD1, PSMA2, PSMA3, PSMB2), and IL-related genes (e.g., CCL5, IL1B, IL32, IL7R, IL6, IL7, CXCL2). Furthermore, METTL14 was found to positively regulate MHC class I gene expression (e.g., HLA-A, -B, -C, -E, -F) in NPC cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings demonstrate, for the first time, that METTL14 modulates the expression of genes related to TNF, IFN, IL, and MHC class I in NPC, proposing a novel role for METTL14 in linking inflammation with cancer, a function that has not been fully elucidated.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 23","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626396","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

Associations Between Ostomy Creation and Health-Related Quality of Life in Colorectal Cancer Patients: A Longitudinal Observational Study 结直肠癌患者造口术与健康相关生活质量的关系：一项纵向观察研究

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-11-28 DOI: 10.1002/cam4.71388

Jerrald Lau, Alyssa Ng, Wei-Ling Koh, Cherie Hui Peh, The Singapore Colorectal Cancer Research Group, Nan Luo, Ker-Kan Tan

Background

Many colorectal cancer (CRC) patients require stoma creation following surgical resection. Stomas can significantly impact health-related quality of life (HRQOL), yet prospective longitudinal studies exploring this are limited. This study aimed to assess HRQOL among CRC patients comparing between those with and without stomas, and examining differences between subgroups.

Methods

This prospective longitudinal study was conducted across five hospitals in Singapore from 2018 to 2023. CRC patients undergoing surgical resection were assessed at six timepoints from diagnosis to 12-month post-surgery. HRQOL was measured using the EORTC QLQ-C30 instrument. Multilevel mixed-effects tobit regression models were used to evaluate HRQOL changes over time and identify significant predictors of HRQOL outcomes.

Results

Among 240 patients, 91 (37.9%) underwent stoma creation. Stoma patients reported significantly poorer HRQOL, particularly in global health status and functional domains at 1 month post-surgery, which persisted into the 3-month timepoint for role (77.43 vs. 86.67, p < 0.05) and emotional (82.11 vs. 90.20, p < 0.05) functioning. Stoma creation predicted reduced physical (β = −10.39, 95% CI: −15.80, −4.97) and role functioning (β = −12.24, 95% CI: −24.38, −0.10). Subgroup differences were mostly non-significant, except for consistently lower cognitive functioning scores in patients with permanent as opposed to temporary stomas (e.g., 1 month; 73.08 vs. 91.19, p < 0.025).

Conclusions

Stoma creation adversely affects HRQOL, particularly in the early postoperative period. Comprehensive post-surgical support addressing physical, psychological, and financial challenges may be crucial to enhance overall HRQOL for stoma patients. Further research should explore tailored support strategies and the effect of early versus delayed stoma closure on HRQOL outcomes.

背景：许多结直肠癌（CRC）患者在手术切除后需要造口。气孔可以显著影响健康相关生活质量（HRQOL），但对此进行前瞻性纵向研究的研究有限。本研究旨在评估结直肠癌患者的HRQOL，比较有和没有造口的患者，并检查亚组之间的差异。方法本前瞻性纵向研究于2018年至2023年在新加坡的五家医院进行。接受手术切除的结直肠癌患者在从诊断到术后12个月的6个时间点进行评估。HRQOL采用EORTC QLQ-C30仪器测定。使用多水平混合效应tobit回归模型来评估HRQOL随时间的变化，并确定HRQOL结果的重要预测因子。结果240例患者中91例（37.9%）行造口术。造口患者报告的HRQOL明显较差，尤其是在术后1个月的整体健康状况和功能领域，这种情况持续到3个月的角色功能（77.43比86.67,p < 0.05）和情绪功能（82.11比90.20,p < 0.05）。造气孔预示着身体机能（β = - 10.39, 95% CI: - 15.80, - 4.97）和角色功能（β = - 12.24, 95% CI: - 24.38, - 0.10）的降低。亚组差异大多不显著，除了永久性造口患者的认知功能评分一直低于暂时性造口患者（例如，1个月；73.08比91.19,p < 0.025）。结论造口对HRQOL有不利影响，尤其是在术后早期。针对生理、心理和财务挑战的综合术后支持可能是提高造口患者整体HRQOL的关键。进一步的研究应该探索量身定制的支持策略以及早期和延迟造口关闭对HRQOL结果的影响。

{"title":"Associations Between Ostomy Creation and Health-Related Quality of Life in Colorectal Cancer Patients: A Longitudinal Observational Study","authors":"Jerrald Lau, Alyssa Ng, Wei-Ling Koh, Cherie Hui Peh, The Singapore Colorectal Cancer Research Group, Nan Luo, Ker-Kan Tan","doi":"10.1002/cam4.71388","DOIUrl":"https://doi.org/10.1002/cam4.71388","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Many colorectal cancer (CRC) patients require stoma creation following surgical resection. Stomas can significantly impact health-related quality of life (HRQOL), yet prospective longitudinal studies exploring this are limited. This study aimed to assess HRQOL among CRC patients comparing between those with and without stomas, and examining differences between subgroups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective longitudinal study was conducted across five hospitals in Singapore from 2018 to 2023. CRC patients undergoing surgical resection were assessed at six timepoints from diagnosis to 12-month post-surgery. HRQOL was measured using the EORTC QLQ-C30 instrument. Multilevel mixed-effects tobit regression models were used to evaluate HRQOL changes over time and identify significant predictors of HRQOL outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 240 patients, 91 (37.9%) underwent stoma creation. Stoma patients reported significantly poorer HRQOL, particularly in global health status and functional domains at 1 month post-surgery, which persisted into the 3-month timepoint for role (77.43 vs. 86.67, <i>p</i> < 0.05) and emotional (82.11 vs. 90.20, <i>p</i> < 0.05) functioning. Stoma creation predicted reduced physical (<i>β</i> = −10.39, 95% CI: −15.80, −4.97) and role functioning (<i>β</i> = −12.24, 95% CI: −24.38, −0.10). Subgroup differences were mostly non-significant, except for consistently lower cognitive functioning scores in patients with permanent as opposed to temporary stomas (e.g., 1 month; 73.08 vs. 91.19, <i>p</i> < 0.025).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Stoma creation adversely affects HRQOL, particularly in the early postoperative period. Comprehensive post-surgical support addressing physical, psychological, and financial challenges may be crucial to enhance overall HRQOL for stoma patients. Further research should explore tailored support strategies and the effect of early versus delayed stoma closure on HRQOL outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 23","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71388","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626318","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

From Gene to Enzyme: Multidimensional Decoding of the GGT Molecular Family and Its Clinical Tumor Diagnosis 从基因到酶：GGT分子家族的多维解码及其临床肿瘤诊断

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-11-28 DOI: 10.1002/cam4.71165

Fei Wang, Jianshan Yang, Feng Zhu, Xuebing Xu, Junpeng Zhao, Xudong Xie, Xuyang He, Yuxuan Huang, Lirong Zhou, Xiaogang Hu, Xiaomin Lu, Mingbing Xiao

<div> <section> <h3> Background</h3> <p>Gamma-glutamyltransferase (GGT) is a membrane-bound enzyme involved in glutathione metabolism and oxidative stress regulation. Although it is traditionally viewed as a liver function marker, emerging evidence suggests that its aberrant expression is closely associated with tumorigenesis, progression, and therapeutic resistance across multiple solid tumors. However, the comprehensive landscape of the GGT gene family and its clinical value in tumor diagnosis and prognosis remain unclear.</p> </section> <section> <h3> Objective</h3> <p>To systematically review the multidimensional roles of the GGT molecular family—including gene variants, mRNA isoforms, enzyme activity, and protein isoforms—in tumor biology and clinical oncology and to evaluate their potential as diagnostic and prognostic biomarkers.</p> </section> <section> <h3> Methods</h3> <p>We conducted a comprehensive literature review (PubMed, CNKI; inception–August 2025) focusing on (1) GGT family gene structure, expression patterns, and regulatory mechanisms; (2) GGT mRNA splice variants and isoforms; (3) GGT enzymatic activity and posttranslational modifications; and (4) clinical studies evaluating GGT as a biomarker in solid tumors. Data were synthesized narratively, emphasizing molecular mechanisms and clinical significance.</p> </section> <section> <h3> Results</h3> <p>The human GGT family comprises 13 homologous genes (e.g., GGT1-7 and GGTLC1-3) localized on chromosomes 20 and 22, which exhibit tissue-specific expression and functional diversity. GGT1 (22q11.23), which is the most extensively studied gene, is highly expressed in renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), gastric cancer (GC), and breast cancer (BRC) and is correlated with poor prognosis and metastasis. GGT5 acts as a tumor suppressor in HCC but promotes progression in gastric cancer via PI3K/AKT pathway activation. GGT7 overexpression predicts poor survival in patients with HCC and glioblastoma. The GGT-II isoform demonstrated 78.7% sensitivity and 92.3% specificity for HCC diagnosis, outperforming AFP (AUC: 0.89 vs. 0.67). Serum GGT activity ≥ 50 U/L independently predicts poor overall survival (OS) in patients with HCC (HR: 1.78, 95% CI: 1.26–2.50). GGT mRNA splice variants (e.g., the GGT-I mRNA-B subtype) enhance early HCC detection when combined with AFP (sensitivity: 98%).</p> </section> <section> <h3> Conclusions</h3> <p>The GGT molecular family plays pleiotro

γ -谷氨酰转移酶（GGT）是一种参与谷胱甘肽代谢和氧化应激调节的膜结合酶。虽然传统上认为它是一种肝功能标志物，但新出现的证据表明，它的异常表达与多种实体瘤的肿瘤发生、进展和治疗耐药性密切相关。然而，GGT基因家族的全面概况及其在肿瘤诊断和预后中的临床价值尚不清楚。目的系统回顾GGT分子家族（包括基因变异、mRNA同工型、酶活性和蛋白同工型）在肿瘤生物学和临床肿瘤学中的多维作用，并评估其作为诊断和预后生物标志物的潜力。方法对相关文献进行综述（PubMed， CNKI; beginning - august 2025），重点关注：(1)GGT家族基因结构、表达模式及调控机制；(2) GGT mRNA剪接变异体和异构体；(3) GGT酶活性及翻译后修饰；(4)评估GGT作为实体瘤生物标志物的临床研究。资料综合叙述，强调分子机制和临床意义。结果人类GGT家族包含13个同源基因（如GGT1-7和GGTLC1-3），分别位于20号和22号染色体上，具有组织特异性表达和功能多样性。GGT1 （22q11.23）是目前研究最广泛的基因，在肾细胞癌（RCC）、肝细胞癌（HCC）、胃癌（GC）、乳腺癌（BRC）中高表达，与预后不良和转移相关。GGT5在HCC中作为肿瘤抑制因子，但通过激活PI3K/AKT通路促进胃癌进展。GGT7过表达预示着HCC和胶质母细胞瘤患者的低生存率。GGT-II亚型对HCC诊断的敏感性为78.7%，特异性为92.3%，优于AFP （AUC: 0.89 vs. 0.67）。血清GGT活性≥50 U/L独立预测HCC患者总生存期（OS）差（HR: 1.78, 95% CI: 1.26-2.50）。GGT mRNA剪接变异体（例如，GGT- i mRNA- b亚型）与AFP联合可增强早期HCC的检测（灵敏度：98%）。结论GGT分子家族通过氧化还原稳态、EMT和免疫调节等多种途径参与肿瘤生物学。GGT1/5/7和GGT-II亚型是多种癌症早期诊断、预后和治疗靶向的有希望的生物标志物。未来的多中心研究应该验证基于GGT的生物标志物面板，并阐明组织特异性GGT功能的机制。

{"title":"From Gene to Enzyme: Multidimensional Decoding of the GGT Molecular Family and Its Clinical Tumor Diagnosis","authors":"Fei Wang, Jianshan Yang, Feng Zhu, Xuebing Xu, Junpeng Zhao, Xudong Xie, Xuyang He, Yuxuan Huang, Lirong Zhou, Xiaogang Hu, Xiaomin Lu, Mingbing Xiao","doi":"10.1002/cam4.71165","DOIUrl":"https://doi.org/10.1002/cam4.71165","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Gamma-glutamyltransferase (GGT) is a membrane-bound enzyme involved in glutathione metabolism and oxidative stress regulation. Although it is traditionally viewed as a liver function marker, emerging evidence suggests that its aberrant expression is closely associated with tumorigenesis, progression, and therapeutic resistance across multiple solid tumors. However, the comprehensive landscape of the GGT gene family and its clinical value in tumor diagnosis and prognosis remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To systematically review the multidimensional roles of the GGT molecular family—including gene variants, mRNA isoforms, enzyme activity, and protein isoforms—in tumor biology and clinical oncology and to evaluate their potential as diagnostic and prognostic biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a comprehensive literature review (PubMed, CNKI; inception–August 2025) focusing on (1) GGT family gene structure, expression patterns, and regulatory mechanisms; (2) GGT mRNA splice variants and isoforms; (3) GGT enzymatic activity and posttranslational modifications; and (4) clinical studies evaluating GGT as a biomarker in solid tumors. Data were synthesized narratively, emphasizing molecular mechanisms and clinical significance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The human GGT family comprises 13 homologous genes (e.g., GGT1-7 and GGTLC1-3) localized on chromosomes 20 and 22, which exhibit tissue-specific expression and functional diversity. GGT1 (22q11.23), which is the most extensively studied gene, is highly expressed in renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), gastric cancer (GC), and breast cancer (BRC) and is correlated with poor prognosis and metastasis. GGT5 acts as a tumor suppressor in HCC but promotes progression in gastric cancer via PI3K/AKT pathway activation. GGT7 overexpression predicts poor survival in patients with HCC and glioblastoma. The GGT-II isoform demonstrated 78.7% sensitivity and 92.3% specificity for HCC diagnosis, outperforming AFP (AUC: 0.89 vs. 0.67). Serum GGT activity ≥ 50 U/L independently predicts poor overall survival (OS) in patients with HCC (HR: 1.78, 95% CI: 1.26–2.50). GGT mRNA splice variants (e.g., the GGT-I mRNA-B subtype) enhance early HCC detection when combined with AFP (sensitivity: 98%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The GGT molecular family plays pleiotro","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 23","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626319","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

Monotherapy With Immune Checkpoint Inhibitors in Patients With Recurrent and/or Metastatic Sinonasal Squamous Cell Carcinoma 免疫检查点抑制剂单药治疗复发性和/或转移性鼻窦鳞状细胞癌

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-11-27 DOI: 10.1002/cam4.71391

Alexander Lein, Thorsten Fuereder, Manuel Stoeth, Agmal Scherzad, Stephan Hackenberg, Julia Schnöll, Lorenz Kadletz-Wanke, Gregor Heiduschka, Archana Jaiswal, Rajiv Bhalla, Lukas Kenner, Faris F. Brkic

Introduction

Sinonasal squamous cell carcinoma (SNSCC) is a rare malignancy with limited data on effective treatment modalities in the recurrent and/or metastatic (r/m) setting. While immune checkpoint inhibitors (ICIs) have shown promise in treating head and neck cancers, in general, their effects in SNSCC remain poorly understood. Furthermore, SNSCC patients are frequently excluded from clinical trials, limiting the evidence base for ICI efficacy in this specific subgroup. Therefore, our study evaluated the efficacy and safety of single-agent ICI therapy in r/m SNSCC.

Methods

We conducted a retrospective multicenter analysis of all r/m SNSCC patients treated with single-agent ICIs from July 2018 to December 2023 at two tertiary reference centers.

Results

A total of 18 patients received either Pembrolizumab (n = 8) or Nivolumab (n = 10) for r/m SNSCC. The overall response rate (ORR) to immunotherapy was 11.1% (2/18), with a disease control rate (DCR) of 27.8% (5/18) and a mean PFS and OS of 11.7 (95% CI: 2.3–21.0) months and 18.9 (95% CI: 8.3–29.5) months respectively. Two (11.1%) immune-related adverse events led to treatment discontinuation. Univariable analysis revealed high pathological grading (p = 0.049) as a negative prognostic factor for PFS. In an exploratory comparison with a larger cohort of 121 patients with r/m SCC of the larynx, oropharynx, hypopharynx, or oral cavity receiving ICI therapy, outcomes in SNSCC appeared broadly similar, with no statistically significant differences in PFS (p = 0.153), OS (p = 0.152), ORR (p = 0.401), or DCR (p = 0.359).

Conclusion

Immunotherapy may represent a treatment option for patients with SNSCC. Given the limited sample size, these results should be interpreted with caution. Our findings highlight the urgent need to include SNSCC patients in future prospective trials to clarify the role of immunotherapy in this underrepresented population.

鼻窦鳞状细胞癌（SNSCC）是一种罕见的恶性肿瘤，关于复发和/或转移（r/m）的有效治疗方法的数据有限。虽然免疫检查点抑制剂（ICIs）在治疗头颈癌方面显示出希望，但总的来说，它们在SNSCC中的作用仍然知之甚少。此外，SNSCC患者经常被排除在临床试验之外，这限制了ICI在这一特定亚组疗效的证据基础。因此，我们的研究评估了单药ICI治疗r/m SNSCC的疗效和安全性。方法我们对2018年7月至2023年12月在两个三级参考中心接受单药ICIs治疗的所有r/m SNSCC患者进行了回顾性多中心分析。结果共有18例患者接受了Pembrolizumab （n = 8）或Nivolumab （n = 10）治疗r/m SNSCC。免疫治疗总有效率（ORR）为11.1%(2/18)，疾病控制率（DCR）为27.8%(5/18)，平均PFS和OS分别为11.7 （95% CI: 2.3-21.0）个月和18.9 （95% CI: 8.3-29.5）个月。2例（11.1%）免疫相关不良事件导致治疗中断。单变量分析显示，高病理分级（p = 0.049）是PFS的负面预后因素。在与接受ICI治疗的121例喉部、口咽、下咽或口腔r/m SCC患者的更大队列的探索性比较中，SNSCC的结果大致相似，PFS （p = 0.153）、OS （p = 0.152）、ORR （p = 0.401）或DCR （p = 0.359）无统计学差异。结论免疫治疗可能是SNSCC患者的一种治疗选择。鉴于有限的样本量，这些结果应谨慎解释。我们的研究结果强调，迫切需要在未来的前瞻性试验中纳入SNSCC患者，以阐明免疫治疗在这一代表性不足的人群中的作用。

{"title":"Monotherapy With Immune Checkpoint Inhibitors in Patients With Recurrent and/or Metastatic Sinonasal Squamous Cell Carcinoma","authors":"Alexander Lein, Thorsten Fuereder, Manuel Stoeth, Agmal Scherzad, Stephan Hackenberg, Julia Schnöll, Lorenz Kadletz-Wanke, Gregor Heiduschka, Archana Jaiswal, Rajiv Bhalla, Lukas Kenner, Faris F. Brkic","doi":"10.1002/cam4.71391","DOIUrl":"https://doi.org/10.1002/cam4.71391","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Sinonasal squamous cell carcinoma (SNSCC) is a rare malignancy with limited data on effective treatment modalities in the recurrent and/or metastatic (r/m) setting. While immune checkpoint inhibitors (ICIs) have shown promise in treating head and neck cancers, in general, their effects in SNSCC remain poorly understood. Furthermore, SNSCC patients are frequently excluded from clinical trials, limiting the evidence base for ICI efficacy in this specific subgroup. Therefore, our study evaluated the efficacy and safety of single-agent ICI therapy in r/m SNSCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective multicenter analysis of all r/m SNSCC patients treated with single-agent ICIs from July 2018 to December 2023 at two tertiary reference centers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 18 patients received either Pembrolizumab (<i>n</i> = 8) or Nivolumab (<i>n</i> = 10) for r/m SNSCC. The overall response rate (ORR) to immunotherapy was 11.1% (2/18), with a disease control rate (DCR) of 27.8% (5/18) and a mean PFS and OS of 11.7 (95% CI: 2.3–21.0) months and 18.9 (95% CI: 8.3–29.5) months respectively. Two (11.1%) immune-related adverse events led to treatment discontinuation. Univariable analysis revealed high pathological grading (<i>p</i> = 0.049) as a negative prognostic factor for PFS. In an exploratory comparison with a larger cohort of 121 patients with r/m SCC of the larynx, oropharynx, hypopharynx, or oral cavity receiving ICI therapy, outcomes in SNSCC appeared broadly similar, with no statistically significant differences in PFS (<i>p</i> = 0.153), OS (<i>p</i> = 0.152), ORR (<i>p</i> = 0.401), or DCR (<i>p</i> = 0.359).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Immunotherapy may represent a treatment option for patients with SNSCC. Given the limited sample size, these results should be interpreted with caution. Our findings highlight the urgent need to include SNSCC patients in future prospective trials to clarify the role of immunotherapy in this underrepresented population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 23","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71391","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626216","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

A Phase 1 Trial of Fimepinostat in Children and Adolescents With Relapsed and Refractory Solid and CNS Tumors 菲美匹诺他在儿童和青少年复发和难治性实体和中枢神经系统肿瘤中的一期临床试验

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-11-27 DOI: 10.1002/cam4.71417

David S. Shulman, Kieuhoa T. Vo, Frank M. Balis, Holly Lindsay, Rochelle Bagatell, Andrew E. Place, Susan N. Chi, Suzanne Shusterman, Suzanne Ezrre, Jeffrey Czaplinski, Ketki Bhushan, Pei-Chi Kao, Wendy B. London, Steven G. DuBois

Background

Fimepinostat, an oral dual inhibitor of histone deacetylase (HDAC) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), has shown activity in preclinical models of Myc-driven pediatric malignancies. This Phase 1 trial aimed to determine the recommended pediatric Phase 2 dose (RPP2D), describe the toxicity profile, and evaluate the pharmacokinetics of fimepinostat in children with relapsed and refractory solid and central nervous system (CNS) tumors.

Methods

This multicenter, Phase 1 study enrolled patients ages 1–21 years with relapsed or refractory solid tumors, CNS tumors, or lymphoma. The dose-escalation phase followed a 3 + 3 design, starting at 27.5 mg/m² and escalating to 45 mg/m². Following dose escalation, three expansion cohorts were opened including cohorts for patients with Myc(n)-driven neuroblastoma, Myc-driven extracranial solid tumors, and diffuse large B-cell lymphoma or Burkitt lymphoma. The pharmacokinetics of fimepinostat and its metabolites were studied after the first dose.

Results

Twenty-six patients were enrolled, with 25 receiving treatment. The median age was 13.6 years (range: 4.1–20.9). In the dose-escalation phase, 12 patients were evaluable for DLT assessment. The RPP2D was initially determined to be 45 mg/m² but was revised to 35 mg/m² after observing DLTs in the dose-expansion phase. Treatment-related adverse events were primarily hematologic and gastrointestinal. No objective responses were observed in 23 evaluable patients. Three patients had stable disease for over four cycles, including a patient with MYCN amplified neuroblastoma with stable disease for 24 cycles. Pharmacokinetic analysis showed significant interpatient variability and rapid conversion of fimepinostat to its metabolites.

Conclusion

Fimepinostat was tolerable at a dose of 35 mg/m² in children with relapsed and refractory solid and CNS tumors, but lacked significant clinical activity. Discovery of drugs to target Myc continues to be a high priority for childhood cancers.

Trial Registration

ClinicalTrials.gov identifier: NCT02909777

Fimepinostat是一种组蛋白去乙酰化酶（HDAC）和磷脂酰肌醇-4,5-二磷酸3激酶（PI3K）的口服双重抑制剂，在myc驱动的儿科恶性肿瘤的临床前模型中显示出活性。该1期临床试验旨在确定儿童2期推荐剂量（RPP2D），描述其毒性特征，并评估非美匹诺他在复发和难治性实体和中枢神经系统（CNS）肿瘤儿童中的药代动力学。方法：这项多中心一期研究纳入了1 - 21岁的复发或难治性实体瘤、中枢神经系统肿瘤或淋巴瘤患者。剂量递增阶段遵循3 + 3设计，从27.5 mg/m2开始，逐步增加到45 mg/m2。剂量递增后，打开三个扩展队列，包括Myc(n)驱动的神经母细胞瘤、Myc驱动的颅外实体瘤和弥漫性大b细胞淋巴瘤或Burkitt淋巴瘤患者的队列。首次给药后，研究了非美匹诺他及其代谢物的药动学。结果纳入26例患者，其中25例接受治疗。中位年龄为13.6岁（范围：4.1-20.9）。在剂量递增阶段，12例患者可进行DLT评估。RPP2D最初确定为45 mg/m2，但在剂量膨胀期观察dlt后修改为35 mg/m2。治疗相关不良事件主要是血液学和胃肠道。23例可评估患者未观察到客观反应。3例患者病情稳定超过4个周期，其中1例MYCN扩增神经母细胞瘤患者病情稳定24个周期。药代动力学分析显示，非美匹诺他在患者间具有显著的差异，且其代谢产物转化迅速。结论35 mg/m2剂量的非美匹诺他对复发和难治性实体瘤和中枢神经系统瘤的儿童是耐受的，但缺乏明显的临床活性。发现针对Myc的药物仍然是儿童癌症的重中之重。试验注册ClinicalTrials.gov标识符：NCT02909777

{"title":"A Phase 1 Trial of Fimepinostat in Children and Adolescents With Relapsed and Refractory Solid and CNS Tumors","authors":"David S. Shulman, Kieuhoa T. Vo, Frank M. Balis, Holly Lindsay, Rochelle Bagatell, Andrew E. Place, Susan N. Chi, Suzanne Shusterman, Suzanne Ezrre, Jeffrey Czaplinski, Ketki Bhushan, Pei-Chi Kao, Wendy B. London, Steven G. DuBois","doi":"10.1002/cam4.71417","DOIUrl":"https://doi.org/10.1002/cam4.71417","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Fimepinostat, an oral dual inhibitor of histone deacetylase (HDAC) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), has shown activity in preclinical models of Myc-driven pediatric malignancies. This Phase 1 trial aimed to determine the recommended pediatric Phase 2 dose (RPP2D), describe the toxicity profile, and evaluate the pharmacokinetics of fimepinostat in children with relapsed and refractory solid and central nervous system (CNS) tumors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This multicenter, Phase 1 study enrolled patients ages 1–21 years with relapsed or refractory solid tumors, CNS tumors, or lymphoma. The dose-escalation phase followed a 3 + 3 design, starting at 27.5 mg/m<sup>2</sup> and escalating to 45 mg/m<sup>2</sup>. Following dose escalation, three expansion cohorts were opened including cohorts for patients with Myc(n)-driven neuroblastoma, Myc-driven extracranial solid tumors, and diffuse large B-cell lymphoma or Burkitt lymphoma. The pharmacokinetics of fimepinostat and its metabolites were studied after the first dose.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-six patients were enrolled, with 25 receiving treatment. The median age was 13.6 years (range: 4.1–20.9). In the dose-escalation phase, 12 patients were evaluable for DLT assessment. The RPP2D was initially determined to be 45 mg/m<sup>2</sup> but was revised to 35 mg/m<sup>2</sup> after observing DLTs in the dose-expansion phase. Treatment-related adverse events were primarily hematologic and gastrointestinal. No objective responses were observed in 23 evaluable patients. Three patients had stable disease for over four cycles, including a patient with <i>MYCN</i> amplified neuroblastoma with stable disease for 24 cycles. Pharmacokinetic analysis showed significant interpatient variability and rapid conversion of fimepinostat to its metabolites.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Fimepinostat was tolerable at a dose of 35 mg/m<sup>2</sup> in children with relapsed and refractory solid and CNS tumors, but lacked significant clinical activity. Discovery of drugs to target Myc continues to be a high priority for childhood cancers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov identifier: NCT02909777</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 23","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71417","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626217","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

“I Missed My Other Oncologist”: Established Relationships as Barriers and Facilitators to Accessing CAR-T and Autologous Transplantation “我错过了我的其他肿瘤学家”：建立关系作为获得CAR-T和自体移植的障碍和促进者

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-11-27 DOI: 10.1002/cam4.71425

Zachary A. K. Frosch, Clark Meshack, Caitlin Meeker, Asya Varshavsky-Yanovsky, Rashmi Khanal, Michael Bromberg, Ashwin Chandar, Emmanuel Quien, Jordan Carter, Shazia K. Nakhoda, Marcus Messmer, Charissa Montgomery, Jason A. Incorvati, Nadia D. Ali, Michael J. Styler, Carolyn Y. Fang

Background

Autologous stem cell transplantation (ASCT) and chimeric antigen receptor T-cell therapy (CAR-T) can provide significant clinical benefit, but are not equally available to all patients. Oncologist continuity and trust are important to patients, and may act as barriers to receipt of therapy. However, detailed data are lacking on the mechanism by which these might affect receipt of therapy, or how this barrier may be overcome.

Methods

We conducted a qualitative interview study with patients with non-Hodgkin lymphoma (NHL), classic Hodgkin lymphoma (cHL) or multiple myeloma (MM) eligible for or treated with ASCT/CAR-T. Participants were recruited from a multi-site academic health system that includes a safety net hospital considered to be one of the most racially inclusive in the country. Interviews were independently coded by two trained coders.

Results

Forty patients participated. Half were female, 65% had multiple myeloma, 45% identified as Black or African American, 22.5% had an income less than $30,000 and 33% were insured with Medicaid. In addition to treatment-specific factors and logistical factors such as housing and transportation, patients identified the need to establish care and trust with a new provider as potential barriers to receipt of therapy. This process could be facilitated by the perception of strong communication and existing relationships between patients' established and new providers.

Conclusions

In addition to logistical and clinical factors, several factors centering around existing and newly required patient-provider relationships may influence patients' acceptance of ASCT/CAR-T. Acceptance may be enhanced by addressing relationship-based barriers in a manner that emphasizes continuity and helps build trust with a new provider, such as by explicitly demonstrating seamless communication among care teams.

自体干细胞移植（ASCT）和嵌合抗原受体t细胞治疗（CAR-T）可以提供显着的临床益处，但并不是所有患者都能平等地获得。肿瘤医生的连续性和信任对病人很重要，也可能成为接受治疗的障碍。然而，关于这些可能影响治疗接受的机制或如何克服这一障碍的详细数据缺乏。方法对符合ASCT/CAR-T治疗条件的非霍奇金淋巴瘤（NHL）、经典霍奇金淋巴瘤（cHL）或多发性骨髓瘤（MM）患者进行定性访谈研究。参与者是从一个多站点的学术卫生系统中招募的，其中包括一个被认为是该国最具种族包容性的安全网医院。访谈由两名训练有素的程序员独立编写。结果40例患者参与。其中一半是女性，65%患有多发性骨髓瘤，45%是黑人或非裔美国人，22.5%的收入低于3万美元，33%的人参加了医疗补助计划。除了治疗特定因素和后勤因素，如住房和交通，患者认为需要与新的提供者建立护理和信任，这是接受治疗的潜在障碍。这一过程可以通过患者现有和新提供者之间强有力的沟通和现有关系来促进。结论除了后勤和临床因素外，围绕现有和新需要的医患关系的几个因素可能影响患者对ASCT/CAR-T的接受。通过强调连续性并帮助与新提供者建立信任的方式来解决基于关系的障碍，例如通过明确展示护理团队之间的无缝沟通，可以提高接受度。

{"title":"“I Missed My Other Oncologist”: Established Relationships as Barriers and Facilitators to Accessing CAR-T and Autologous Transplantation","authors":"Zachary A. K. Frosch, Clark Meshack, Caitlin Meeker, Asya Varshavsky-Yanovsky, Rashmi Khanal, Michael Bromberg, Ashwin Chandar, Emmanuel Quien, Jordan Carter, Shazia K. Nakhoda, Marcus Messmer, Charissa Montgomery, Jason A. Incorvati, Nadia D. Ali, Michael J. Styler, Carolyn Y. Fang","doi":"10.1002/cam4.71425","DOIUrl":"https://doi.org/10.1002/cam4.71425","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Autologous stem cell transplantation (ASCT) and chimeric antigen receptor T-cell therapy (CAR-T) can provide significant clinical benefit, but are not equally available to all patients. Oncologist continuity and trust are important to patients, and may act as barriers to receipt of therapy. However, detailed data are lacking on the mechanism by which these might affect receipt of therapy, or how this barrier may be overcome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a qualitative interview study with patients with non-Hodgkin lymphoma (NHL), classic Hodgkin lymphoma (cHL) or multiple myeloma (MM) eligible for or treated with ASCT/CAR-T. Participants were recruited from a multi-site academic health system that includes a safety net hospital considered to be one of the most racially inclusive in the country. Interviews were independently coded by two trained coders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Forty patients participated. Half were female, 65% had multiple myeloma, 45% identified as Black or African American, 22.5% had an income less than $30,000 and 33% were insured with Medicaid. In addition to treatment-specific factors and logistical factors such as housing and transportation, patients identified the need to establish care and trust with a new provider as potential barriers to receipt of therapy. This process could be facilitated by the perception of strong communication and existing relationships between patients' established and new providers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In addition to logistical and clinical factors, several factors centering around existing and newly required patient-provider relationships may influence patients' acceptance of ASCT/CAR-T. Acceptance may be enhanced by addressing relationship-based barriers in a manner that emphasizes continuity and helps build trust with a new provider, such as by explicitly demonstrating seamless communication among care teams.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 23","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71425","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626287","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

Efficacy of Almonertinib Versus Osimertinib as the First-Line Treatment for Non-Small Cell Lung Cancer With EGFR L858R Mutation and Prognostic Analysis: A Retrospective Comparative Cohort Study Almonertinib与Osimertinib一线治疗EGFR L858R突变非小细胞肺癌的疗效及预后分析：一项回顾性比较队列研究

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-11-27 DOI: 10.1002/cam4.71422

Xiujing Yao, Ruyue Li, Xue Dong, Ying Li, Yintao Li

Objectives

Epidermal growth factor receptor (EGFR)–specific tyrosine kinase inhibitors show less efficacy against the EGFR L858R mutation than EGFR 19del, but no current head-to-head clinical trials have been performed comparing the efficacy of almonertinib and osimertinib. Therefore, our study compared the efficacy of these drugs against the EGFR L858R mutation.

Materials and Methods

A total of 200 patients with non-small cell lung cancer harboring the EGFR L858R mutation were enrolled. Among these patients, 121 received 80 mg of osimertinib, while the other 79 received 110 mg of almonertinib once daily. The primary end point was progression-free survival (PFS). The secondary end points were continued response rate and safety.

Results

The median PFS was 18.5 months (95% confidence interval [CI] 16.1–22.5) for osimertinib and 19.4 months (95% CI 13.8–NA) for almonertinib, with a hazard ratio (HR) of 0.92 (95% CI 0.62–1.73), p = 0.69. Forest plots of subgroup analyses showed no significant difference in the median PFS between the almonertinib and osimertinib groups across the subgroups. Osimertinib and almonertinib demonstrated good efficacy in the treatment of patients with brain metastases. The median PFS was 18.6 months (95% CI 15.6–22.8) for patients with brain metastases and 17.1 months (95% CI 14.1–28.6) for those without brain metastases, p = 0.89. Patients with programmed cell death ligand 1 (PD-L1) expression between 1% and 49% and PD-L1 expression < 1% showed no significant differences for their median PFS. The continued response rates between almonertinib and osimertinib were comparable. The differences between almonertinib and osimertinib were minimal.

Conclusion

Both almonertinib and osimertinib demonstrated good efficacy in patients with brain metastases, and PD-L1 expression was not associated with the prognosis of EGFR L858R mutant NSCLC. Finally, no significant difference between osimertinib and almonertinib for the treatment of patients with EGFR L858R mutations was observed. Both options remain viable for these patients.

表皮生长因子受体（EGFR）特异性酪氨酸激酶抑制剂对EGFR L858R突变的疗效不如EGFR 19del，但目前还没有对阿莫尼替尼和奥西替尼的疗效进行正面对比的临床试验。因此，我们的研究比较了这些药物对EGFR L858R突变的疗效。材料与方法共纳入200例携带EGFR L858R突变的非小细胞肺癌患者。在这些患者中，121人接受80mg的奥西替尼治疗，另外79人接受110 mg的阿蒙替尼治疗，每天一次。主要终点为无进展生存期（PFS）。次要终点是持续缓解率和安全性。结果奥西替尼的中位PFS为18.5个月（95%可信区间[CI] 16.1-22.5），阿尔莫替尼的中位PFS为19.4个月（95% CI 13.8-NA），风险比（HR）为0.92 (95% CI 0.62-1.73), p = 0.69。亚组分析的森林图显示，almonertinib组和osimertinib组在亚组间的中位PFS无显著差异。奥西替尼和阿蒙尼替尼治疗脑转移患者疗效良好。脑转移患者的中位PFS为18.6个月（95% CI 15.6-22.8），无脑转移患者的中位PFS为17.1个月（95% CI 14.1-28.6）， p = 0.89。程序性细胞死亡配体1 （PD-L1）表达在1%到49%之间的患者和PD-L1表达在1%之间的患者的中位PFS没有显著差异。almonertinib和osimertinib的持续缓解率具有可比性。almonertinib和osimertinib之间的差异很小。结论almonertinib和osimertinib对脑转移患者均有较好的疗效，且PD-L1表达与EGFR L858R突变型NSCLC的预后无相关性。最后，对于EGFR L858R突变患者，奥西替尼与阿蒙尼替尼的治疗效果无显著差异。这两种选择对这些患者来说都是可行的。

{"title":"Efficacy of Almonertinib Versus Osimertinib as the First-Line Treatment for Non-Small Cell Lung Cancer With EGFR L858R Mutation and Prognostic Analysis: A Retrospective Comparative Cohort Study","authors":"Xiujing Yao, Ruyue Li, Xue Dong, Ying Li, Yintao Li","doi":"10.1002/cam4.71422","DOIUrl":"https://doi.org/10.1002/cam4.71422","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Epidermal growth factor receptor (EGFR)–specific tyrosine kinase inhibitors show less efficacy against the EGFR L858R mutation than EGFR 19del, but no current head-to-head clinical trials have been performed comparing the efficacy of almonertinib and osimertinib. Therefore, our study compared the efficacy of these drugs against the EGFR L858R mutation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>A total of 200 patients with non-small cell lung cancer harboring the EGFR L858R mutation were enrolled. Among these patients, 121 received 80 mg of osimertinib, while the other 79 received 110 mg of almonertinib once daily. The primary end point was progression-free survival (PFS). The secondary end points were continued response rate and safety.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The median PFS was 18.5 months (95% confidence interval [CI] 16.1–22.5) for osimertinib and 19.4 months (95% CI 13.8–NA) for almonertinib, with a hazard ratio (HR) of 0.92 (95% CI 0.62–1.73), <i>p</i> = 0.69. Forest plots of subgroup analyses showed no significant difference in the median PFS between the almonertinib and osimertinib groups across the subgroups. Osimertinib and almonertinib demonstrated good efficacy in the treatment of patients with brain metastases. The median PFS was 18.6 months (95% CI 15.6–22.8) for patients with brain metastases and 17.1 months (95% CI 14.1–28.6) for those without brain metastases, <i>p</i> = 0.89. Patients with programmed cell death ligand 1 (PD-L1) expression between 1% and 49% and PD-L1 expression < 1% showed no significant differences for their median PFS. The continued response rates between almonertinib and osimertinib were comparable. The differences between almonertinib and osimertinib were minimal.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Both almonertinib and osimertinib demonstrated good efficacy in patients with brain metastases, and PD-L1 expression was not associated with the prognosis of EGFR L858R mutant NSCLC. Finally, no significant difference between osimertinib and almonertinib for the treatment of patients with EGFR L858R mutations was observed. Both options remain viable for these patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 23","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71422","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626215","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