Jose A. Monteiro MD, Yong Teng PhD, Nicole C. Schmitt MD, Nabil F. Saba MD
{"title":"Integrating systemic therapy into larynx preservation: Lessons from 3 decades of progress","authors":"Jose A. Monteiro MD, Yong Teng PhD, Nicole C. Schmitt MD, Nabil F. Saba MD","doi":"10.1002/cncr.70258","DOIUrl":"10.1002/cncr.70258","url":null,"abstract":"","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Approximately half of patients with chronic myeloid leukemia (CML) who attempted tyrosine kinase inhibitor (TKI) discontinuation for the first time experienced molecular relapse and restarted TKIs. Although several studies have already investigated first treatment-free remission (TFR) attempts (TFR1), few previously published articles have focused on the plausibility and predictors of second TFR (TFR2).
Methods
To evaluate the feasibility and likelihood of TFR2 success in real-life, 90 patients with CML regularly followed in 23 Italian hematological centers were analyzed; these patients reattempted TKI discontinuation after a first failed attempt.
Results
Forty-five (50.0%) patients lost major molecular response after a median of 4.0 months off therapy, whereas 45 (50.0%) remained treatment-free for a median of 18.8 months. In univariate analysis, there was no association between TFR2 and the following variables: age, gender, Sokal risk score, BCR::ABL1 transcript type, prior interferon exposure, type and number of previous TKIs, resistance to any prior TKIs, and TKI switching after TFR1. In contrast, factors identified as associated with TFR2 success included a lower ELTS risk score, a longer time from TFR1 to molecular relapse (≥3 months), as well as a longer TKI treatment and deep molecular response (DMR) duration (≥4 years) before TFR2.
Conclusions
While confirming the critical prognostic role of ELTS risk and TKI treatment and DMR duration even before TFR2, this real-life study provides further information to support the safety of a second effort to discontinue TKIs in patients with CML, as a failed first attempt does not appear to preclude a second successful one.
{"title":"Second attempt to discontinue TKI after molecular relapse in patients with chronic myeloid leukemia: A real-life Italian multicenter study","authors":"Alessandra Iurlo MD, PhD, Daniele Cattaneo MD, Carmen Fava MD, PhD, Fausto Castagnetti MD, PhD, Massimiliano Bonifacio MD, Mariella D’Adda MD, Maria Cristina Miggiano MD, Isabella Capodanno MD, Chiara Elena MD, Luciano Levato MD, Anna Rita Scortechini MD, PhD, Francesca Lunghi MD, Marianna Caramella MD, Nicola Orofino MD, Margherita Maffioli MD, Valentina Bellani MD, Valentina Bonuomo MD, Selene Grano MD, Giulia Cotilli MD, Emilia Scalzulli MD, Matteo Dalmazzo MD, Sabrina Leonetti Crescenzi MD, Luigiana Luciano MD, Bruno Martino MD, Tamara Intermesoli MD, Davide Rapezzi MD, Gianni Binotto MD, Mario Tiribelli MD, Dario Consonni MD, PhD, Fabrizio Pane MD, Giuseppe Saglio MD, Carlo Gambacorti-Passerini MD, Massimo Breccia MD, Gianantonio Rosti MD","doi":"10.1002/cncr.70261","DOIUrl":"10.1002/cncr.70261","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Approximately half of patients with chronic myeloid leukemia (CML) who attempted tyrosine kinase inhibitor (TKI) discontinuation for the first time experienced molecular relapse and restarted TKIs. Although several studies have already investigated first treatment-free remission (TFR) attempts (TFR1), few previously published articles have focused on the plausibility and predictors of second TFR (TFR2).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To evaluate the feasibility and likelihood of TFR2 success in real-life, 90 patients with CML regularly followed in 23 Italian hematological centers were analyzed; these patients reattempted TKI discontinuation after a first failed attempt.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Forty-five (50.0%) patients lost major molecular response after a median of 4.0 months off therapy, whereas 45 (50.0%) remained treatment-free for a median of 18.8 months. In univariate analysis, there was no association between TFR2 and the following variables: age, gender, Sokal risk score, <i>BCR::ABL1</i> transcript type, prior interferon exposure, type and number of previous TKIs, resistance to any prior TKIs, and TKI switching after TFR1. In contrast, factors identified as associated with TFR2 success included a lower ELTS risk score, a longer time from TFR1 to molecular relapse (≥3 months), as well as a longer TKI treatment and deep molecular response (DMR) duration (≥4 years) before TFR2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>While confirming the critical prognostic role of ELTS risk and TKI treatment and DMR duration even before TFR2, this real-life study provides further information to support the safety of a second effort to discontinue TKIs in patients with CML, as a failed first attempt does not appear to preclude a second successful one.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>Adjuvant chemoradiation did not significantly improve recurrence-free survival (RFS) or overall survival (OS) in comparison with radiation alone in patients with intermediate-risk, early-stage cervical cancer after radical hysterectomy and lymphadenectomy according to results of the NRG Oncology/GOG-263/KGOG 1008 trial.<span><sup>1</sup></span></p><p>“As it was designed and evaluated, this was a negative study,” says study researcher Charles A. Leath III, MD, a professor in the Department of Obstetrics and Gynecology at the University of Alabama at Birmingham. “The addition of chemotherapy to radiation did not improve outcomes in terms of 3-year RFS, which was the primary endpoint.”</p><p>Historically, the addition of chemotherapy, specifically cisplatin, to radiotherapy was noted to improve clinical outcomes for patients with different clinical scenarios of cervical cancer, Dr Leath explains. In 1999, the National Cancer Institute (NCI) issued a clinical announcement recommending that clinicians consider adding chemotherapy to radiation therapy rather than using radiation alone for certain patients with cervical cancer.<span><sup>2</sup></span> Since then, chemoradiation has become the standard of care for patients with locally advanced cervical cancer as well as high-risk features after radical hysterectomy. However, the role of adjuvant chemoradiation in patients with intermediate risk factors has not been fully investigated, Dr Leath says.</p><p>The phase 3 NRG Oncology/GOG-263/KGOG 1008 trial enrolled 340 postsurgical patients with stage I–IIA cervical cancer with intermediate risk factors. Patients were randomly assigned to receive either adjuvant chemoradiation with cisplatin or radiation alone. Of the 340 randomized patients, 316 were eligible.</p><p>The 3-year RFS rates of the study arms were similar: 88.5% for chemoradiation and 85.4% for radiation alone. Although the results were not statistically significant, survival outcomes favored chemoradiation for both RFS (hazard ratio [HR], 0.698; 95% CI, 0.408–1.192; <i>p</i> = .09) and OS (HR, 0.586; 95% CI, 0.286–1.199; <i>p</i> = .07). Interestingly, the recurrence rates of the two arms were not statistically different (15.8% for radiation therapy vs. 12.7% for chemoradiation therapy [CRT]), and there was not a significant difference in the pattern of recurrence.</p><p>Dr Leath notes that the study did not accrue the planned number of patients, so “there remains a chance that had the trial been able to accrue the planned number of patients, we would have seen not only a clinically significant difference [in survival] but a statistically significant difference.”</p><p>Commenting on the results, Linda R. Duska, MD, the Lawrence W. Penniston, MD, Family Endowed Professor of Women’s Oncology Research at the University of Virginia School of Medicine in Charlottesville, Virginia, says that this trial was indeed an important one asking an important question. Although it was negative, clinician
根据NRG Oncology/GOG-263/KGOG 1008试验的结果，与单独放疗相比，辅助放化疗没有显著提高根治性子宫切除术和淋巴结切除术后中高危早期宫颈癌患者的无复发生存期（RFS）或总生存期（OS）。“从设计和评估的角度来看，这是一项消极的研究，”研究人员查尔斯·a·利斯三世医学博士说，他是伯明翰阿拉巴马大学妇产学系的教授。“在放疗的基础上增加化疗并没有改善3年的RFS，这是主要终点。”Leath博士解释说，从历史上看，在放疗的基础上增加化疗，特别是顺铂，可以改善不同临床情况的宫颈癌患者的临床结果。1999年，美国国家癌症研究所（NCI）发布了一份临床声明，建议临床医生考虑在放射治疗中加入化疗，而不是对某些宫颈癌患者单独使用放射治疗从那时起，放化疗成为局部晚期宫颈癌患者以及根治性子宫切除术后高危患者的标准治疗方法。然而，Leath博士说，辅助放化疗在具有中等危险因素的患者中的作用尚未得到充分调查。NRG Oncology/GOG-263/KGOG 1008 3期临床试验招募了340例具有中等危险因素的I-IIA期宫颈癌术后患者。患者被随机分配接受顺铂辅助放化疗或单独放化疗。在340名随机患者中，316名符合条件。研究组的3年RFS率相似：放化疗组为88.5%，单纯放化疗组为85.4%。虽然结果无统计学意义，但生存结果对RFS（危险比[HR]， 0.698; 95% CI, 0.408-1.192; p = 0.09）和OS（危险比[HR]， 0.586; 95% CI, 0.286-1.199; p = 0.07）均有利放化疗。有趣的是，两组的复发率无统计学差异（放疗组为15.8%，放化疗组为12.7% [CRT]），复发方式也无显著差异。利思博士指出，这项研究并没有累积到计划的患者数量，所以“如果试验能够累积到计划的患者数量，我们不仅会看到临床上的显著差异，而且会看到统计学上的显著差异。”Linda R. Duska，医学博士，Lawrence W. Penniston，医学博士，弗吉尼亚州夏洛茨维尔市弗吉尼亚大学医学院女性肿瘤研究的家庭捐赠教授，在评论结果时说，这项试验确实是一个重要的试验，提出了一个重要的问题。虽然结果是负面的，但临床医生仍然可以从这项试验中学到很多东西。这表明了nci资助研究的重要性，以及发表“负面”结果的价值。Duska博士说：“这项重要且设计良好的试验增加了我们在这一领域的前瞻性文献，但我不认为它明确地回答了这个问题。”“这项试验显示出放化疗组有改善的趋势，但不能对CRT的RFS和OS的改善做出结论性的陈述。”Leath博士和他的同事们进行了亚组分析，以确定是否有哪一组患者从添加顺铂中获益更多。有趣的是，在适形外部放射治疗与调强放射治疗（IMRT）的患者中，似乎有一种倾向于放化疗而不是单独放疗的趋势。Duska博士说：“人们可以假设，如果患者无法获得现代放射治疗（IMRT），临床医生可能会考虑在该方案中添加铂。”“我会将这些信息纳入我与个别患者的共同决策讨论中。”Duska博士补充说，事实上，研究结果为与患者进行共同决策对话提供了额外的知识。在与具有这些中间危险因素的患者交谈时，她会建议“有可能，但不确定，增加化疗可能会增加RFS并改善OS，但我们不确定。”我们也知道它会增加化疗期间的不良事件，降低生活质量。”在试验中，单独接受放疗的患者比接受放化疗的患者经历了更少的3级或4级不良事件（15% vs 43%; p < 0.01）。这些包括更多的3级或4级血液毒性，如贫血、中性粒细胞减少症和血小板减少症，在分配放化疗的患者中。Leath博士说：“令人欣慰的是，生活质量数据显示，在完成治疗后相对较短的时间内，大多数问题恢复到基线水平。”“没有明显的长期毒性。 在另一篇文章中，Leath博士和他的同事发表了NRG肿瘤学/GOG-263试验的患者报告结果（PROs）分配给放化疗或单独放疗的患者在基线和3,7和36周完成PRO/QOL评估。研究显示，尽管两组患者的生活质量都有所下降，但那些接受放化疗的患者的短期恶化程度更大。然而，对于两个研究组，生活质量和生活质量在36周后都恢复到基线。根据Leath博士的说法，人们必须看看这些数据，并承认在分配给放化疗和单独放疗的患者的生存结果上存在差异。“它们在统计学上没有显著差异，但如果患者多一些或事件少一些，那么p值可能会达到。”05或。2004年，突然之间，这成为了事实上的全球护理标准，”Leath博士说。
{"title":"Adjuvant chemoradiation offers minimal survival improvements over radiation alone in intermediate-risk, early cervical cancer","authors":"Leah Lawrence","doi":"10.1002/cncr.70207","DOIUrl":"10.1002/cncr.70207","url":null,"abstract":"<p>Adjuvant chemoradiation did not significantly improve recurrence-free survival (RFS) or overall survival (OS) in comparison with radiation alone in patients with intermediate-risk, early-stage cervical cancer after radical hysterectomy and lymphadenectomy according to results of the NRG Oncology/GOG-263/KGOG 1008 trial.<span><sup>1</sup></span></p><p>“As it was designed and evaluated, this was a negative study,” says study researcher Charles A. Leath III, MD, a professor in the Department of Obstetrics and Gynecology at the University of Alabama at Birmingham. “The addition of chemotherapy to radiation did not improve outcomes in terms of 3-year RFS, which was the primary endpoint.”</p><p>Historically, the addition of chemotherapy, specifically cisplatin, to radiotherapy was noted to improve clinical outcomes for patients with different clinical scenarios of cervical cancer, Dr Leath explains. In 1999, the National Cancer Institute (NCI) issued a clinical announcement recommending that clinicians consider adding chemotherapy to radiation therapy rather than using radiation alone for certain patients with cervical cancer.<span><sup>2</sup></span> Since then, chemoradiation has become the standard of care for patients with locally advanced cervical cancer as well as high-risk features after radical hysterectomy. However, the role of adjuvant chemoradiation in patients with intermediate risk factors has not been fully investigated, Dr Leath says.</p><p>The phase 3 NRG Oncology/GOG-263/KGOG 1008 trial enrolled 340 postsurgical patients with stage I–IIA cervical cancer with intermediate risk factors. Patients were randomly assigned to receive either adjuvant chemoradiation with cisplatin or radiation alone. Of the 340 randomized patients, 316 were eligible.</p><p>The 3-year RFS rates of the study arms were similar: 88.5% for chemoradiation and 85.4% for radiation alone. Although the results were not statistically significant, survival outcomes favored chemoradiation for both RFS (hazard ratio [HR], 0.698; 95% CI, 0.408–1.192; <i>p</i> = .09) and OS (HR, 0.586; 95% CI, 0.286–1.199; <i>p</i> = .07). Interestingly, the recurrence rates of the two arms were not statistically different (15.8% for radiation therapy vs. 12.7% for chemoradiation therapy [CRT]), and there was not a significant difference in the pattern of recurrence.</p><p>Dr Leath notes that the study did not accrue the planned number of patients, so “there remains a chance that had the trial been able to accrue the planned number of patients, we would have seen not only a clinically significant difference [in survival] but a statistically significant difference.”</p><p>Commenting on the results, Linda R. Duska, MD, the Lawrence W. Penniston, MD, Family Endowed Professor of Women’s Oncology Research at the University of Virginia School of Medicine in Charlottesville, Virginia, says that this trial was indeed an important one asking an important question. Although it was negative, clinician","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 2","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70207","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008061","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}
Mckenzie DiLeo MD, Samantha Oglesby BS, Cheuk Hong Leung MS, Kristen E. Pauken PhD, Sahira Farooq MD, Lauren E. Haydu PhD, MPH, Shelby L. Kubicki MD, Rebeca Martinez MD, Macartney Welborn MD, Sana Zahiruddin MD, Jun Zou MD, PhD, Kai Cao MS, MD, Anisha B. Patel MD
Background
While immune checkpoint inhibitors (ICIs) have shown significant efficacy, a common side effect is cutaneous immune-related adverse events (irAEs). This study focuses on exploring the association between specific human leukocyte antigen (HLA) alleles and the development of cutaneous irAEs in melanoma patients undergoing ICI monotherapy and combination therapy. As certain HLA types are indicative of susceptibility to autoimmune diseases, it was hypothesized that HLA typing could serve as a potential screening tool for identifying patients at increased risk for developing irAEs.
Methods
A retrospective chart review was performed of 515 patients with melanoma who underwent ICI therapy, either as monotherapy or in combination, and had HLA typing available. This analysis spans from 2003 to 2023 with a focus on cutaneous irAEs. Statistical analyses were conducted to assess the association between HLA alleles and irAEs.
Results
Our analysis revealed that the HLA-B*51:01 allele was associated with a higher risk of cutaneous irAEs after adjusting for ICI regimen (hazard ratio: 1.71 [95% CI, 1.12–2.61], p = .013.)
Conclusion
This is the largest study to link an HLA allele with ICI-induced cutaneous irAEs. The findings may support the use of HLA typing as an initial screen for developing irAEs, providing a simple, straightforward metric that can be rapidly performed on patients prior to initiation of ICIs. However, further research is needed across different cancer and toxicity types.
背景：虽然免疫检查点抑制剂（ICIs）已经显示出显著的疗效，但一个常见的副作用是皮肤免疫相关不良事件（irAEs）。本研究的重点是探讨特异性人类白细胞抗原（HLA）等位基因与接受ICI单药和联合治疗的黑色素瘤患者皮肤irAEs发展之间的关系。由于某些HLA类型表明对自身免疫性疾病的易感性，因此假设HLA分型可以作为一种潜在的筛查工具，用于识别发生irae风险增加的患者。方法：对515例黑色素瘤患者进行回顾性图表回顾，这些患者接受了ICI治疗，无论是单一治疗还是联合治疗，并有HLA分型。该分析的时间跨度为2003年至2023年，重点是皮肤irAEs。统计分析HLA等位基因与irae之间的关系。结果：我们的分析显示，在调整ICI方案后，HLA-B*51:01等位基因与皮肤irAEs的高风险相关（风险比：1.71 [95% CI, 1.12-2.61], p = 0.013）。结论：这是将HLA等位基因与ici诱导的皮肤irAEs联系起来的最大规模的研究。这些发现可能支持将HLA分型作为开发irae的初始筛选，提供了一个简单、直接的指标，可以在开始ICIs之前对患者快速执行。然而，需要对不同的癌症和毒性类型进行进一步的研究。
{"title":"Retrospective analysis of cutaneous immune-related adverse events following checkpoint inhibitor therapy in melanoma patients reveals increased risk associated with the HLA-B*51:01 allele","authors":"Mckenzie DiLeo MD, Samantha Oglesby BS, Cheuk Hong Leung MS, Kristen E. Pauken PhD, Sahira Farooq MD, Lauren E. Haydu PhD, MPH, Shelby L. Kubicki MD, Rebeca Martinez MD, Macartney Welborn MD, Sana Zahiruddin MD, Jun Zou MD, PhD, Kai Cao MS, MD, Anisha B. Patel MD","doi":"10.1002/cncr.70262","DOIUrl":"10.1002/cncr.70262","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>While immune checkpoint inhibitors (ICIs) have shown significant efficacy, a common side effect is cutaneous immune-related adverse events (irAEs). This study focuses on exploring the association between specific human leukocyte antigen (HLA) alleles and the development of cutaneous irAEs in melanoma patients undergoing ICI monotherapy and combination therapy. As certain HLA types are indicative of susceptibility to autoimmune diseases, it was hypothesized that HLA typing could serve as a potential screening tool for identifying patients at increased risk for developing irAEs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective chart review was performed of 515 patients with melanoma who underwent ICI therapy, either as monotherapy or in combination, and had HLA typing available. This analysis spans from 2003 to 2023 with a focus on cutaneous irAEs. Statistical analyses were conducted to assess the association between HLA alleles and irAEs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our analysis revealed that the HLA-B*51:01 allele was associated with a higher risk of cutaneous irAEs after adjusting for ICI regimen (hazard ratio: 1.71 [95% CI, 1.12–2.61], <i>p</i> = .013.)</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This is the largest study to link an HLA allele with ICI-induced cutaneous irAEs. The findings may support the use of HLA typing as an initial screen for developing irAEs, providing a simple, straightforward metric that can be rapidly performed on patients prior to initiation of ICIs. However, further research is needed across different cancer and toxicity types.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70262","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008221","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}
Yibin Qiu MD, Long Wu MD, Weifeng Cai MD, Minyan Chen MD, Meichen Jiang MD, Yali Wang MD PhD, Shunyi Liu MD, Peng He MD, Yuxiang Lin MD PhD, Lili Chen MD, Yinghong Yang MD, Chuan Wang MD PhD, Jie Zhang MD PhD, Fangmeng Fu MD PhD
Background
The prognostic relevance of HER2-low, HER2-ultralow, and null status in HER2-negative early breast cancer (eBC), and its evolution during neoadjuvant chemotherapy (NAC), remains unclear.
Methods
The authors analyzed 810 HER2-negative eBC patients (2011–2021) with centrally confirmed pre- and post-NAC HER2 status. Pathologic complete response (pCR, ypT0/is ypN0) rates were analyzed using logistic regression, and invasive disease-free survival (iDFS) and overall survival (OS) were evaluated via multivariable Cox proportional hazards models.
Results
HER2-null tumors demonstrated significantly higher rates of hormone receptor negativity, grade III histology, and Ki-67 ≥20% compared to HER2-low subgroup (p < .05 for all). The pCR rates were 8.4% (HER2-low), 20.4% (HER2-ultralow), and 25.0% (HER2-null), respectively. HER2 expression inversely correlated with pCR rates across the entire cohort (odds ratio, 0.75; 95% confidence interval [CI], 0.58–0.98; p for trend = .033). After a median follow-up of 70.8 months, survival analysis indicated that higher HER2 expression was associated with significantly improved iDFS (hazard ratio, 0.72; 95% CI, 0.62–0.83) and OS (hazard ratio, 0.67; 95% CI, 0.57–0.80) in the overall population (p for trend <.001 for both). Following NAC, nearly 41.0% of baseline HER2-null tumors converted to HER2-low or ultralow status. Notably, post-NAC HER2 status remained predictive of improved survival in patients with residual disease (iDFS, hazard ratio, 0.72; 95% CI, 0.62–0.84; OS, hazard ratio, 0.65; 95% CI, 0.55–0.78; p for trend <.001 for both).
Conclusion
HER2 expression levels (low/ultralow/null) stratify prognosis in HER2-negative eBC. The dynamic evolution of HER2 status following NAC and its prognostic utility highlights the importance of reassessing HER2 status in residual disease in HER2-negative eBC.
{"title":"The evolution and prognostic impact of HER2-low, HER2-ultralow, and HER2-null status in HER2-negative early breast cancer: A pre– to post–neoadjuvant chemotherapy study","authors":"Yibin Qiu MD, Long Wu MD, Weifeng Cai MD, Minyan Chen MD, Meichen Jiang MD, Yali Wang MD PhD, Shunyi Liu MD, Peng He MD, Yuxiang Lin MD PhD, Lili Chen MD, Yinghong Yang MD, Chuan Wang MD PhD, Jie Zhang MD PhD, Fangmeng Fu MD PhD","doi":"10.1002/cncr.70269","DOIUrl":"10.1002/cncr.70269","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The prognostic relevance of HER2-low, HER2-ultralow, and null status in HER2-negative early breast cancer (eBC), and its evolution during neoadjuvant chemotherapy (NAC), remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The authors analyzed 810 HER2-negative eBC patients (2011–2021) with centrally confirmed pre- and post-NAC HER2 status. Pathologic complete response (pCR, ypT0/is ypN0) rates were analyzed using logistic regression, and invasive disease-free survival (iDFS) and overall survival (OS) were evaluated via multivariable Cox proportional hazards models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>HER2-null tumors demonstrated significantly higher rates of hormone receptor negativity, grade III histology, and Ki-67 ≥20% compared to HER2-low subgroup (<i>p</i> < .05 for all). The pCR rates were 8.4% (HER2-low), 20.4% (HER2-ultralow), and 25.0% (HER2-null), respectively. HER2 expression inversely correlated with pCR rates across the entire cohort (odds ratio, 0.75; 95% confidence interval [CI], 0.58–0.98; <i>p</i> for trend = .033). After a median follow-up of 70.8 months, survival analysis indicated that higher HER2 expression was associated with significantly improved iDFS (hazard ratio, 0.72; 95% CI, 0.62–0.83) and OS (hazard ratio, 0.67; 95% CI, 0.57–0.80) in the overall population (<i>p</i> for trend <.001 for both). Following NAC, nearly 41.0% of baseline HER2-null tumors converted to HER2-low or ultralow status. Notably, post-NAC HER2 status remained predictive of improved survival in patients with residual disease (iDFS, hazard ratio, 0.72; 95% CI, 0.62–0.84; OS, hazard ratio, 0.65; 95% CI, 0.55–0.78; <i>p</i> for trend <.001 for both).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>HER2 expression levels (low/ultralow/null) stratify prognosis in HER2-negative eBC. The dynamic evolution of HER2 status following NAC and its prognostic utility highlights the importance of reassessing HER2 status in residual disease in HER2-negative eBC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jingxuan Zhao PhD, MPH, Ilana Graetz PhD, David Howard PhD, K. Robin Yabroff PhD, Joseph Lipscomb PhD
Background
The objective of this study was to examine the associations between federal and state short-term limited-duration (STLD) insurance plan regulations and timely cancer treatment initiation.
Methods
Adults aged 18–64 years newly diagnosed with female breast, colorectal, or non–small cell lung cancers in 2017–2019 were identified from the National Cancer Database. Patients were categorized into five groups on the basis of their state of residence at diagnosis: (1) the state continuously prohibited STLD plans; (2) the state stopped offering STLD plans after the 2018 federal rule; (3) the state kept the same 3-month limit on STLD plans before and after the 2018 federal rule; (4) the state expanded the sale of STLD plans but imposed more stringent regulation of STLD plans; and (5) the state expanded the sale of STLD plans and did not impose additional regulation. A difference-in-differences (DID) approach examined the changes in the percentages of patients initiating treatment within 30 days of their cancer diagnosis before and after the 2018 federal rule.
Results
For all cancers combined, compared to patients living in states continuously prohibiting STLD plans, a net decrease was observed in the percentages receiving timely treatment among patients living in states continuously limiting STLD plans to 3 months (DID, −1.61 percentage points [ppts]; 95% confidence interval [CI], −2.86 to −0.37 ppts), in states with less stringent regulations (DID, −2.09 ppts; 95% CI, −3.33 to −0.84 ppts), and in states with the least stringent regulations (DID, −2.48 ppts; 95% CI, −3.52 to −1.44 ppts).
Conclusions
Limited or no state regulation of STLD plans after the 2018 federal expansion of plan coverage duration was associated with decreases in timely cancer treatment initiation.
{"title":"Federal and state policies regulating short-term limited-duration insurance plans and timely cancer treatment initiation","authors":"Jingxuan Zhao PhD, MPH, Ilana Graetz PhD, David Howard PhD, K. Robin Yabroff PhD, Joseph Lipscomb PhD","doi":"10.1002/cncr.70190","DOIUrl":"10.1002/cncr.70190","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The objective of this study was to examine the associations between federal and state short-term limited-duration (STLD) insurance plan regulations and timely cancer treatment initiation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Adults aged 18–64 years newly diagnosed with female breast, colorectal, or non–small cell lung cancers in 2017–2019 were identified from the National Cancer Database. Patients were categorized into five groups on the basis of their state of residence at diagnosis: (1) the state continuously prohibited STLD plans; (2) the state stopped offering STLD plans after the 2018 federal rule; (3) the state kept the same 3-month limit on STLD plans before and after the 2018 federal rule; (4) the state expanded the sale of STLD plans but imposed more stringent regulation of STLD plans; and (5) the state expanded the sale of STLD plans and did not impose additional regulation. A difference-in-differences (DID) approach examined the changes in the percentages of patients initiating treatment within 30 days of their cancer diagnosis before and after the 2018 federal rule.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>For all cancers combined, compared to patients living in states continuously prohibiting STLD plans, a net decrease was observed in the percentages receiving timely treatment among patients living in states continuously limiting STLD plans to 3 months (DID, −1.61 percentage points [ppts]; 95% confidence interval [CI], −2.86 to −0.37 ppts), in states with less stringent regulations (DID, −2.09 ppts; 95% CI, −3.33 to −0.84 ppts), and in states with the least stringent regulations (DID, −2.48 ppts; 95% CI, −3.52 to −1.44 ppts).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Limited or no state regulation of STLD plans after the 2018 federal expansion of plan coverage duration was associated with decreases in timely cancer treatment initiation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 2","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhehao Xiao MD, PhD, Zhongguo Liang MD, PhD, Hejing Huang MM, Yumei Qin MM, Shiting Huang MD, PhD, Jingni Wei MD, PhD, Ying Guan MD, PhD, Youqin Du MD, PhD, Fang Su MD, PhD, Kaiguo Li MM, Yang Liu MD, PhD, Junbao Wei MM, Fanyan Zeng MD, PhD, Ye Li MD, PhD, Chunmi Wei MD, PhD, Yanlin Mo MD, PhD, Binbin Yu MD, PhD, Song Qu MD, PhD
Background
Improving the efficacy of retreatment for locally recurrent nasopharyngeal carcinoma (rNPC) and extending patient survival are urgently required for the clinical prevention and treatment of NPC. This study explored the efficacy and safety of toripalimab in combination with concurrent chemoradiotherapy (CCRT) for the treatment of rNPC.
Methods
This single-arm, Phase 2 trial included patients with rNPC who met the inclusion criteria as confirmed by pathology or imaging. The patients received toripalimab combined with CCRT. The primary end point was the objective response rate (ORR) of the patients. Secondary end points included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety profile.
Results
Between April 2020 and September 2023, 40 patients with rNPC were recruited. The best response of ORR after radiotherapy was 87.5% (95% confidence interval [CI]: 72.0–95.0), with a DCR of 100%. The median PFS for rNPC was 18.1 months (95% CI, 15.2–28.8). The 1-year, 2-year, and 3-year PFS rates were 68.2%, 41.3%, and 15.5%, respectively. The median OS for rNPC was 28.3 months (95% CI, 18.6–Not Available [NA]). The 1-year, 2-year, and 3-year OS rates were 69.7%, 53.9%, 44.8%. The most common acute toxicities were hematological toxicities, including lymphopenia (100%) and anemia (92.5%), whereas the most common late toxicities were dry mouth (60.0%) and nasopharyngeal wall necrosis (40.0%). Fatal epistaxis was the cause of death in 22.5% of patients.
Conclusion
Toripalimab plus CCRT demonstrates antitumor efficacy in rNPC. The observed 22.5% rate of fatal epistaxis indicates that its potential benefits must be carefully weighed against this serious treatment-related risk.
{"title":"Toripalimab plus concurrent chemoradiotherapy for recurrent nasopharyngeal carcinoma: A single-arm, phase 2 clinical trial","authors":"Zhehao Xiao MD, PhD, Zhongguo Liang MD, PhD, Hejing Huang MM, Yumei Qin MM, Shiting Huang MD, PhD, Jingni Wei MD, PhD, Ying Guan MD, PhD, Youqin Du MD, PhD, Fang Su MD, PhD, Kaiguo Li MM, Yang Liu MD, PhD, Junbao Wei MM, Fanyan Zeng MD, PhD, Ye Li MD, PhD, Chunmi Wei MD, PhD, Yanlin Mo MD, PhD, Binbin Yu MD, PhD, Song Qu MD, PhD","doi":"10.1002/cncr.70257","DOIUrl":"10.1002/cncr.70257","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Improving the efficacy of retreatment for locally recurrent nasopharyngeal carcinoma (rNPC) and extending patient survival are urgently required for the clinical prevention and treatment of NPC. This study explored the efficacy and safety of toripalimab in combination with concurrent chemoradiotherapy (CCRT) for the treatment of rNPC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This single-arm, Phase 2 trial included patients with rNPC who met the inclusion criteria as confirmed by pathology or imaging. The patients received toripalimab combined with CCRT. The primary end point was the objective response rate (ORR) of the patients. Secondary end points included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety profile.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Between April 2020 and September 2023, 40 patients with rNPC were recruited. The best response of ORR after radiotherapy was 87.5% (95% confidence interval [CI]: 72.0–95.0), with a DCR of 100%. The median PFS for rNPC was 18.1 months (95% CI, 15.2–28.8). The 1-year, 2-year, and 3-year PFS rates were 68.2%, 41.3%, and 15.5%, respectively. The median OS for rNPC was 28.3 months (95% CI, 18.6–Not Available [NA]). The 1-year, 2-year, and 3-year OS rates were 69.7%, 53.9%, 44.8%. The most common acute toxicities were hematological toxicities, including lymphopenia (100%) and anemia (92.5%), whereas the most common late toxicities were dry mouth (60.0%) and nasopharyngeal wall necrosis (40.0%). Fatal epistaxis was the cause of death in 22.5% of patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Toripalimab plus CCRT demonstrates antitumor efficacy in rNPC. The observed 22.5% rate of fatal epistaxis indicates that its potential benefits must be carefully weighed against this serious treatment-related risk.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 2","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Insights into the role of chemotherapy and thyroid peroxidase antibodies in risk for primary hypothyroidism among childhood cancer survivors","authors":"Angela Delaney MD","doi":"10.1002/cncr.70260","DOIUrl":"10.1002/cncr.70260","url":null,"abstract":"","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 2","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145996824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hang-Ning Zhou MS, Tong Li MS, Yi-Nan Peng MS, Hui Li MD, PhD, Zhi-Cong Wu PhD, Yu-Ying Fan BS, Ann D. King FRCR, MD, Allan Hildesheim PhD, Wei Ling BS, Zhiwei Liu PhD, Su-Mei Cao MD, PhD
Background
The long-term impact of magnetic resonance imaging (MRI) on nasopharyngeal carcinoma (NPC) detection in screening remains unclear as a result of limited follow-up.
Methods
A prospective population-based screening study was conducted in Southern China from October 2014 to November 2018 among Epstein-Barr virus (EBV)–seropositive individuals aged 30–69 years. EBV-seropositive participants underwent both endoscopy and MRI. Suspicious findings from either modality triggered a second endoscopy with biopsy. Followup for cancer diagnoses was completed via multiple methods in October 2023. Primary end points included the 5-year NPC detection rate (overall and by stage) and the false-negative rate. Secondary end points were sensitivity, specificity, positive predictive value (PPV), and referral rate.
Results
The analysis included 814 individuals (455 females; 56%) with a median age of 53 years (interquartile range, 46–60 years). Thirty-two NPC cases were detected (30 via MRI; 21 via endoscopy) over 5 years. MRI showed a significantly higher overall NPC detection rate (36.9 [95% CI, 25.9–52.1] vs. 25.8 [95% CI, 16.9–39.1] per 1000; p = .007) and early-stage tumor detection (20.9 [95% CI, 13.1–27.1] vs. 12.3 [95% CI, 6.7–22.5] per 1000; p = .020) than endoscopy. MRI also demonstrated a lower false-negative rate (3.0 [95% CI, 0.8–11.0] vs. 14.9 [95% CI, 8.4–26.5] per 1000; p = .024) and higher sensitivity (93.8% vs. 65.6%; p = .007) but lower specificity (84.0% vs. 92.8%; p < .001) and PPV (19.6% vs. 27.6%; p = .019).
Conclusions
Single MRI demonstrated superior NPC detection versus endoscopy, particularly for early-stage tumors, in high-risk populations during a 5-year period, which suggests the potential for extending the rescreening interval to 5 years for MRI-negative individuals.
背景：由于随访有限，磁共振成像（MRI）对鼻咽癌（NPC）筛查的长期影响尚不清楚。方法：2014年10月至2018年11月，在中国南方对30-69岁EBV血清阳性个体进行了基于人群的前瞻性筛查研究。ebv血清阳性的参与者接受了内窥镜检查和MRI检查。任何一种模式的可疑发现都引发了第二次内镜活检。于2023年10月通过多种方法完成癌症诊断的随访。主要终点包括5年NPC检出率（总体和分期）和假阴性率。次要终点为敏感性、特异性、阳性预测值（PPV）和转诊率。结果：共纳入814例患者，其中女性455例，占56%，中位年龄53岁（四分位数范围46-60岁）。5年来共发现32例鼻咽癌（MRI 30例，内镜21例）。MRI显示整体鼻咽癌检出率（36.9 [95% CI, 25.9-52.1]比25.8 [95% CI, 16.9-39.1] / 1000, p = 0.007）和早期肿瘤检出率（20.9 [95% CI, 13.1-27.1]比12.3 [95% CI, 6.7-22.5] / 1000, p = 0.020）明显高于内镜检查。MRI也显示出较低的假阴性率（3.0 [95% CI, 0.8-11.0] vs. 14.9 [95% CI, 8.4-26.5] / 1000; p = 0.024）和较高的敏感性（93.8% vs. 65.6%; p = 0.007），但较低的特异性(84.0% vs. 92.8%； p结论：在高风险人群中，5年期间，单次MRI显示出比内窥镜更好的鼻咽癌检测，特别是早期肿瘤，这表明将MRI阴性个体的重新筛查间隔延长至5年的潜力。
{"title":"Five-year comparison of magnetic resonance imaging and endoscopy for nasopharyngeal carcinoma detection among high-risk populations undergoing screening","authors":"Hang-Ning Zhou MS, Tong Li MS, Yi-Nan Peng MS, Hui Li MD, PhD, Zhi-Cong Wu PhD, Yu-Ying Fan BS, Ann D. King FRCR, MD, Allan Hildesheim PhD, Wei Ling BS, Zhiwei Liu PhD, Su-Mei Cao MD, PhD","doi":"10.1002/cncr.70256","DOIUrl":"10.1002/cncr.70256","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The long-term impact of magnetic resonance imaging (MRI) on nasopharyngeal carcinoma (NPC) detection in screening remains unclear as a result of limited follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A prospective population-based screening study was conducted in Southern China from October 2014 to November 2018 among Epstein-Barr virus (EBV)–seropositive individuals aged 30–69 years. EBV-seropositive participants underwent both endoscopy and MRI. Suspicious findings from either modality triggered a second endoscopy with biopsy. Followup for cancer diagnoses was completed via multiple methods in October 2023. Primary end points included the 5-year NPC detection rate (overall and by stage) and the false-negative rate. Secondary end points were sensitivity, specificity, positive predictive value (PPV), and referral rate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The analysis included 814 individuals (455 females; 56%) with a median age of 53 years (interquartile range, 46–60 years). Thirty-two NPC cases were detected (30 via MRI; 21 via endoscopy) over 5 years. MRI showed a significantly higher overall NPC detection rate (36.9 [95% CI, 25.9–52.1] vs. 25.8 [95% CI, 16.9–39.1] per 1000; <i>p</i> = .007) and early-stage tumor detection (20.9 [95% CI, 13.1–27.1] vs. 12.3 [95% CI, 6.7–22.5] per 1000; <i>p</i> = .020) than endoscopy. MRI also demonstrated a lower false-negative rate (3.0 [95% CI, 0.8–11.0] vs. 14.9 [95% CI, 8.4–26.5] per 1000; <i>p</i> = .024) and higher sensitivity (93.8% vs. 65.6%; <i>p</i> = .007) but lower specificity (84.0% vs. 92.8%; <i>p</i> < .001) and PPV (19.6% vs. 27.6%; <i>p</i> = .019).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Single MRI demonstrated superior NPC detection versus endoscopy, particularly for early-stage tumors, in high-risk populations during a 5-year period, which suggests the potential for extending the rescreening interval to 5 years for MRI-negative individuals.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 2","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiubing Zhang MD, Dayang Wang MD, Guanzheng Liu PhD, Chaojie Bu MD, Guangming Lv MD, Minghao Li MD, Shaobin Wei MD, Ziyue Zhang MD, Yushuai Gao MD, Zhaoyue Yan MD, Chunxiao Ma PhD, Ruijiao Zhao PhD, Meiyun Wang PhD, Yujie Shi PhD, Xingyao Bu PhD
Background
This study evaluated tislelizumab combined with low-dose bevacizumab in recurrent glioblastoma (rGBM), assessing efficacy, safety, and mechanisms of immune escape.
Methods
This randomized phase 2 trial divided patients into treatment arms with distinct strategies. Longitudinal tumor in situ fluid (TISF) samples were collected for molecular analysis to monitor genome evolution. Immunohistochemical markers in paired primary and recurrent tumor specimens were analyzed to assess therapy-induced immune resistance.
Results
A total of 109 patients were included, with 59 in the control group and 50 in the experimental group. No grade 4 adverse events or treatment discontinuations occurred in the experimental group. The experimental group demonstrated a median overall survival of 13.3 months, compared to 6.6 months in the control group. The objective response rate and disease control rate were 32.6% and 79.1%, respectively. Post-treatment TISF analysis revealed a 68.4% reduction in detectable genomic alterations. Immunophenotypic analysis of paired tumor samples showed increased infiltration of CD163+ macrophages and elevated GDF-15 expression in recurrent tumors.
Conclusion
This study shows that combining tislelizumab and low-dose bevacizumab improves survival in rGBM patients with good safety and tolerability. Dynamic changes in TISF-based molecular markers reflect genomic evolution and predict prognosis. Increased CD163+ cell infiltration in recurrent tumors may activate M2 macrophages, promoting tumor growth and immune evasion. Elevated GDF-15 levels may further suppress antitumor immunity, facilitating immune escape.
{"title":"Dynamic signature for the effectiveness of anti–PD-1 therapy combined with vascular normalization therapy in recurrent glioblastoma: A randomized phase 2 trial","authors":"Jiubing Zhang MD, Dayang Wang MD, Guanzheng Liu PhD, Chaojie Bu MD, Guangming Lv MD, Minghao Li MD, Shaobin Wei MD, Ziyue Zhang MD, Yushuai Gao MD, Zhaoyue Yan MD, Chunxiao Ma PhD, Ruijiao Zhao PhD, Meiyun Wang PhD, Yujie Shi PhD, Xingyao Bu PhD","doi":"10.1002/cncr.70253","DOIUrl":"10.1002/cncr.70253","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This study evaluated tislelizumab combined with low-dose bevacizumab in recurrent glioblastoma (rGBM), assessing efficacy, safety, and mechanisms of immune escape.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This randomized phase 2 trial divided patients into treatment arms with distinct strategies. Longitudinal tumor in situ fluid (TISF) samples were collected for molecular analysis to monitor genome evolution. Immunohistochemical markers in paired primary and recurrent tumor specimens were analyzed to assess therapy-induced immune resistance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 109 patients were included, with 59 in the control group and 50 in the experimental group. No grade 4 adverse events or treatment discontinuations occurred in the experimental group. The experimental group demonstrated a median overall survival of 13.3 months, compared to 6.6 months in the control group. The objective response rate and disease control rate were 32.6% and 79.1%, respectively. Post-treatment TISF analysis revealed a 68.4% reduction in detectable genomic alterations. Immunophenotypic analysis of paired tumor samples showed increased infiltration of CD163<sup>+</sup> macrophages and elevated GDF-15 expression in recurrent tumors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study shows that combining tislelizumab and low-dose bevacizumab improves survival in rGBM patients with good safety and tolerability. Dynamic changes in TISF-based molecular markers reflect genomic evolution and predict prognosis. Increased CD163<sup>+</sup> cell infiltration in recurrent tumors may activate M2 macrophages, promoting tumor growth and immune evasion. Elevated GDF-15 levels may further suppress antitumor immunity, facilitating immune escape.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 2","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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