Glucose-6-phosphate dehydrogenase (G6PD) deficiency impairs cellular redox balance through reduced NADPH production and is the most common enzymatic disorder-causing anemia. Venetoclax combined with azacitidine (Ven-Aza) targets leukemic stem cells by disrupting oxidative phosphorylation and inducing mitochondrial stress. This study hypothesized that G6PD deficiency may enhance the efficacy of Ven-Aza in acute myeloid leukemia (AML) by reducing leukemic cell metabolic resilience.
Methods
The authors studied 73 consecutive patients with newly diagnosed (ND) AML treated with Ven-Aza. G6PD activity was systematically assessed at diagnosis in all patients and categorized as normal (n = 47), borderline (n = 11), or deficient (n = 15).
Results
Composite complete remission rates were 93% in the G6PD deficient group versus 69% in the normal/borderline group (p = .03). Patients with G6PD deficiency had a significantly longer median overall survival (23.8 months; 95% confidence interval [CI], 8.9–38.7), as compared to 8.96 months (95% CI, 2.9–15.0) in the normal/borderline group (p = .034). In multivariate analysis, G6PD-deficiency was associated with improved survival as compared to patients with normal G6PD activity (hazard ratio, 0.417; 95% CI, 0.181–0.965, p = .043). No significant differences were observed across groups in rates of febrile neutropenia, pneumonia, sepsis, or grade 3–4 cytopenia.
Conclusion
G6PD deficiency is associated with higher response rates and improved survival in patients with ND-AML treated with Ven-Aza. These findings support G6PD deficiency as a potential biomarker of therapeutic sensitivity to Ven-AZA and may uncover metabolic vulnerabilities in AML with potential therapeutic implications.
{"title":"Glucose-6-phosphate dehydrogenase deficiency is associated with improved survival in patients with acute myeloid leukemia treated with venetoclax and azacitidine","authors":"Shira Buchrits MD, Alon Rozental MD, Noa Korngold BSc, Ofer Algor MD, Shirly Partouche PhD, Galit Granot PhD, Pia Raanani MD, Ofir Wolach MD","doi":"10.1002/cncr.70265","DOIUrl":"10.1002/cncr.70265","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Glucose-6-phosphate dehydrogenase (G6PD) deficiency impairs cellular redox balance through reduced NADPH production and is the most common enzymatic disorder-causing anemia. Venetoclax combined with azacitidine (Ven-Aza) targets leukemic stem cells by disrupting oxidative phosphorylation and inducing mitochondrial stress. This study hypothesized that G6PD deficiency may enhance the efficacy of Ven-Aza in acute myeloid leukemia (AML) by reducing leukemic cell metabolic resilience.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The authors studied 73 consecutive patients with newly diagnosed (ND) AML treated with Ven-Aza. G6PD activity was systematically assessed at diagnosis in all patients and categorized as normal (<i>n</i> = 47), borderline (<i>n</i> = 11), or deficient (<i>n</i> = 15).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Composite complete remission rates were 93% in the G6PD deficient group versus 69% in the normal/borderline group (<i>p</i> = .03). Patients with G6PD deficiency had a significantly longer median overall survival (23.8 months; 95% confidence interval [CI], 8.9–38.7), as compared to 8.96 months (95% CI, 2.9–15.0) in the normal/borderline group (<i>p</i> = .034). In multivariate analysis, G6PD-deficiency was associated with improved survival as compared to patients with normal G6PD activity (hazard ratio, 0.417; 95% CI, 0.181–0.965, <i>p</i> = .043). No significant differences were observed across groups in rates of febrile neutropenia, pneumonia, sepsis, or grade 3–4 cytopenia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>G6PD deficiency is associated with higher response rates and improved survival in patients with ND-AML treated with Ven-Aza. These findings support G6PD deficiency as a potential biomarker of therapeutic sensitivity to Ven-AZA and may uncover metabolic vulnerabilities in AML with potential therapeutic implications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12824983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146016730","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}
Rachel E. Aubrey HBSc, BScN, RN, Pamela Psarianos PhD, MSc, HBSc, Anna T. Santiago MSc, MPH, BSc, Anthony M. Griffin MSc, Peter C. Ferguson MD, MSc, FRCSC, Abha A. Gupta MD, MSc, FRCPC, Hagit Peretz Soroka PhD, David B. Shultz MD, PhD, FRCPC
Background
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas with a 5-year survival rate of approximately 50%, secondary to their metastatic potential and resistance to therapy. MPNSTs can arise sporadically, as a late toxicity from therapeutic radiotherapy, or in patients with neurofibromatosis type 1 (NF1). Prior studies have demonstrated conflicting results regarding the prognosis of NF1 associated MPNST compared to non-NF1 associated MPNST (NF0). The authors hypothesized that NF1-associated MPNSTs metastasize at a higher rate and are therefore associated with worse clinical outcomes.
Methods
The authors collected data from 166 MPNST patients included in the Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) database. Of these, 54 had NF1. Patient demographics, overall survival (OS), cumulative incidence of progression or relapse (CIPR), and cumulative incidence of disease metastasis (CIDM) were assessed.
Results
Patients with NF1 were younger (p < .001) and had larger tumors at MPNST diagnosis (p < .001). Two-year OS was lower, and CIPR and CIDM were higher in NF1-associated compared to NF0 MPNST. NF1 status, stage at diagnosis, tumor size, and positive surgical margins were adversely correlated to OS. Tumor location was an adverse prognostic factor for CIPR, and tumor size was the only adverse predictor for the CIDM in patients who underwent surgery.
Conclusion
In summary, this study suggests that patients with NF1-associated MPNSTs experience worse outcomes. NF1 associated MPNSTs were larger and arose in locations less amenable to negative (R0) resections. Among resectable tumors, CIDM, the primary driver of survival in patients initially diagnosed with localized disease, was correlated to tumor size but not NF1 status.
{"title":"Outcomes following definitive treatment of malignant peripheral nerve sheath tumor are significantly worse for patients with neurofibromatosis type 1: A Canadian Sarcoma Research and Clinical Collaboration study","authors":"Rachel E. Aubrey HBSc, BScN, RN, Pamela Psarianos PhD, MSc, HBSc, Anna T. Santiago MSc, MPH, BSc, Anthony M. Griffin MSc, Peter C. Ferguson MD, MSc, FRCSC, Abha A. Gupta MD, MSc, FRCPC, Hagit Peretz Soroka PhD, David B. Shultz MD, PhD, FRCPC","doi":"10.1002/cncr.70263","DOIUrl":"10.1002/cncr.70263","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas with a 5-year survival rate of approximately 50%, secondary to their metastatic potential and resistance to therapy. MPNSTs can arise sporadically, as a late toxicity from therapeutic radiotherapy, or in patients with neurofibromatosis type 1 (NF1). Prior studies have demonstrated conflicting results regarding the prognosis of NF1 associated MPNST compared to non-NF1 associated MPNST (NF0). The authors hypothesized that NF1-associated MPNSTs metastasize at a higher rate and are therefore associated with worse clinical outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The authors collected data from 166 MPNST patients included in the Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) database. Of these, 54 had NF1. Patient demographics, overall survival (OS), cumulative incidence of progression or relapse (CIPR), and cumulative incidence of disease metastasis (CIDM) were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with NF1 were younger (<i>p</i> < .001) and had larger tumors at MPNST diagnosis (<i>p</i> < .001). Two-year OS was lower, and CIPR and CIDM were higher in NF1-associated compared to NF0 MPNST. NF1 status, stage at diagnosis, tumor size, and positive surgical margins were adversely correlated to OS. Tumor location was an adverse prognostic factor for CIPR, and tumor size was the only adverse predictor for the CIDM in patients who underwent surgery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In summary, this study suggests that patients with NF1-associated MPNSTs experience worse outcomes. NF1 associated MPNSTs were larger and arose in locations less amenable to negative (R0) resections. Among resectable tumors, CIDM, the primary driver of survival in patients initially diagnosed with localized disease, was correlated to tumor size but not NF1 status.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12824984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146016755","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}
<p>Patients with metastatic breast cancer or metastatic non–small cell lung cancer (NSCLC) with leptomeningeal metastatic disease (LMD) who underwent proton craniospinal irradiation (pCSI) had improved central nervous system progression-free survival (CNS-PFS) in comparison with patients who underwent involved-field radiotherapy (IFRT) according to the results of a phase 2 study.<span><sup>1</sup></span></p><p>Receipt of pCSI resulted in a median 5.9-month improvement in CNS-PFS in comparison with the receipt of IFRT. This improvement, combined with an improvement in overall survival (OS) and a trend toward improved self-reported daily function, led study researcher Jonathan T. Yang, MD, PhD, a radiation oncology resident at Memorial Sloan Kettering Cancer Center in New York, New York (at the time of the study), and his colleagues to conclude “that patients should be considered for pCSI if available.”</p><p>The study included 98 patients with NSCLC or breast cancer with LMD. Patients with other solid tumors were enrolled as an exploratory pCSI cohort. Patients were randomly assigned 2:1 to pCSI or IFRT. The median follow-up was 26.8 months.</p><p>At 6 months, the patients assigned to IFRT had a cumulative incidence rate of CNS progression of 88% versus 22% for the patients who received pCSI (<i>p</i> < .001). The median CNS-PFS was 8.2 months with pCSI and 2.3 months with IFRT (<i>p</i> < .001). The median OS more than doubled in the pCSI arm in comparison with the IFRT arm (11 vs. 4.9 months; <i>p</i> = .04).</p><p>All patients in the exploratory arm of other solid tumor types received pCSI; the median CNS-PFS was 5.8 months, and the median OS was 7.0 months.</p><p>In discussing the results, Helen A. Shih, MD, MS, MPH, a radiation oncologist at Massachusetts General Hospital of Mass General Brigham in Boston, outlines the existing treatment options for patients with LMD.</p><p>“Once someone has LMD, disease can be anywhere in the cerebrospinal fluid, and if we want to treat it in entirety, we have to treat the entire spinal cord and brain and all the other tissue/fluid within the thecal sac. But doing so with a traditional photon technique is generally considered too toxic to be beneficial,” says Dr Shih. “Instead, we just treat the areas that are symptomatic. If a patient has bad headaches, for example, we may do whole brain irradiation.”</p><p>This approach of treating symptomatic areas is a palliative approach and was compared in this study with a more “curative” or comprehensive approach to managing the CNS disease with pCSI.</p><p>“It was predictable to have a positive study because we are treating the entire thecal sac, meaning all the CNS disease, versus a treatment that was never intended to result in a survival benefit,” says Dr Shih. “It is not apples to apples.”</p><p>Fortunately, these findings resulted in the initiation of the NRG-BN014 trial, which will compare pCSI and photon IFRT at a larger scale multi-institutionally to v
根据一项2期研究的结果，接受质子颅脊髓照射（pCSI）的转移性乳腺癌或转移性非小细胞肺癌（NSCLC）合并轻脑膜转移性疾病（LMD）的患者与接受受病灶放疗（IFRT）的患者相比，中枢神经系统无进展生存期（CNS-PFS）得到改善。与接受IFRT相比，接受pCSI导致CNS-PFS的中位改善5.9个月。这种改善，结合总生存期（OS）的改善和自我报告的日常功能改善的趋势，领导研究人员Jonathan T. Yang，医学博士，纽约纪念斯隆凯特琳癌症中心的放射肿瘤学住院医师（研究时），和他的同事得出结论：“如果有可能，患者应该考虑进行pCSI。”该研究纳入了98例伴有LMD的非小细胞肺癌或乳腺癌患者。其他实体肿瘤患者被纳入探索性pCSI队列。患者按2:1随机分配至pCSI或IFRT组。中位随访时间为26.8个月。在6个月时，分配给IFRT的患者的累积CNS进展发生率为88%，而接受pCSI的患者为22% （p < .001）。中位CNS-PFS为pCSI组8.2个月，IFRT组2.3个月（p < .001）。与IFRT组相比，pCSI组的中位生存期增加了一倍以上（11个月vs. 4.9个月；p = .04）。其他实体瘤类型探查组均行pCSI；中位CNS-PFS为5.8个月，中位OS为7.0个月。在讨论结果时，波士顿麻省总医院的放射肿瘤学家Helen a . Shih，医学博士，硕士，公共卫生硕士，概述了LMD患者现有的治疗方案。“一旦有人患有LMD，疾病可能出现在脑脊液的任何地方，如果我们想要全面治疗，我们必须治疗整个脊髓、大脑以及硬膜囊内的所有其他组织/液体。但是用传统的光子技术这样做通常被认为毒性太大而无益，”Shih博士说。“相反，我们只治疗有症状的部位。例如，如果患者头痛严重，我们可能会对其进行全脑照射。”这种治疗症状区域的方法是一种姑息性方法，在本研究中与pCSI治疗中枢神经系统疾病的更“治愈”或更全面的方法进行了比较。Shih博士说：“这是一个可以预测的阳性研究，因为我们治疗的是整个鞘囊，也就是所有的中枢神经系统疾病，而不是一种从未打算导致生存获益的治疗。”“这不是苹果对苹果。”幸运的是，这些发现导致了NRG-BN014试验的启动，该试验将在更大规模的多机构中比较pCSI和光子IFRT，以验证领先癌症中心的发现。“我们实际上已经有几十年没有做过光子治疗了，但随着质子治疗的进步，光子技术也在进步，”施博士说。“现在我们可以更准确地比较这些技术，也可以考虑使用更高度共形和现在广泛使用的强度调制放射治疗技术的光子CSI，更具体地说，是体积调制电弧治疗的亚型，与更有历史意义的光子CSI技术相比，它的副作用要小得多。”研究结果的另一个重要考虑因素是，大多数患者（88%）是新诊断的LMD。施博士说，在她的机构接受LMD放射治疗的患者通常经过大量的预处理，因为他们在CSI之前尝试了多种全身治疗。“[在这项研究中，]大多数患者在被诊断为LMD后立即接受放射治疗，我不确定所有患者都会这样做，”Shih博士说。鉴于越来越多的免疫治疗和靶向治疗方案，其中一些已显示出治疗中枢神经系统转移的有效性，患者可能会在决定尝试CSI之前选择全身治疗方案。这样做的好处是可以治疗中枢神经系统以外的潜在疾病，并避免辐射的其他风险，例如辐射整个大脑可能产生的神经认知影响。
{"title":"Proton craniospinal irradiation option for leptomeningeal metastatic disease","authors":"Leah Lawrence","doi":"10.1002/cncr.70209","DOIUrl":"10.1002/cncr.70209","url":null,"abstract":"<p>Patients with metastatic breast cancer or metastatic non–small cell lung cancer (NSCLC) with leptomeningeal metastatic disease (LMD) who underwent proton craniospinal irradiation (pCSI) had improved central nervous system progression-free survival (CNS-PFS) in comparison with patients who underwent involved-field radiotherapy (IFRT) according to the results of a phase 2 study.<span><sup>1</sup></span></p><p>Receipt of pCSI resulted in a median 5.9-month improvement in CNS-PFS in comparison with the receipt of IFRT. This improvement, combined with an improvement in overall survival (OS) and a trend toward improved self-reported daily function, led study researcher Jonathan T. Yang, MD, PhD, a radiation oncology resident at Memorial Sloan Kettering Cancer Center in New York, New York (at the time of the study), and his colleagues to conclude “that patients should be considered for pCSI if available.”</p><p>The study included 98 patients with NSCLC or breast cancer with LMD. Patients with other solid tumors were enrolled as an exploratory pCSI cohort. Patients were randomly assigned 2:1 to pCSI or IFRT. The median follow-up was 26.8 months.</p><p>At 6 months, the patients assigned to IFRT had a cumulative incidence rate of CNS progression of 88% versus 22% for the patients who received pCSI (<i>p</i> < .001). The median CNS-PFS was 8.2 months with pCSI and 2.3 months with IFRT (<i>p</i> < .001). The median OS more than doubled in the pCSI arm in comparison with the IFRT arm (11 vs. 4.9 months; <i>p</i> = .04).</p><p>All patients in the exploratory arm of other solid tumor types received pCSI; the median CNS-PFS was 5.8 months, and the median OS was 7.0 months.</p><p>In discussing the results, Helen A. Shih, MD, MS, MPH, a radiation oncologist at Massachusetts General Hospital of Mass General Brigham in Boston, outlines the existing treatment options for patients with LMD.</p><p>“Once someone has LMD, disease can be anywhere in the cerebrospinal fluid, and if we want to treat it in entirety, we have to treat the entire spinal cord and brain and all the other tissue/fluid within the thecal sac. But doing so with a traditional photon technique is generally considered too toxic to be beneficial,” says Dr Shih. “Instead, we just treat the areas that are symptomatic. If a patient has bad headaches, for example, we may do whole brain irradiation.”</p><p>This approach of treating symptomatic areas is a palliative approach and was compared in this study with a more “curative” or comprehensive approach to managing the CNS disease with pCSI.</p><p>“It was predictable to have a positive study because we are treating the entire thecal sac, meaning all the CNS disease, versus a treatment that was never intended to result in a survival benefit,” says Dr Shih. “It is not apples to apples.”</p><p>Fortunately, these findings resulted in the initiation of the NRG-BN014 trial, which will compare pCSI and photon IFRT at a larger scale multi-institutionally to v","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.70209","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008142","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}
<p>Once daily low-dose aspirin significantly reduced the cumulative incidence of colorectal cancer recurrence at 3 years in comparison with a placebo in patients with <i>PIK3CA</i> hotspot mutations in Exon 9 or 20, with a similar benefit found for patients with other somatic alterations in the PI3K pathway, according to results of the ALASCCA trial.<span><sup>1</sup></span></p><p>Anna Martling, MD, PhD, a professor of surgery at the Karolinska Institutet in Stockholm, Sweden, and her colleagues identified 1103 patients with stage I–III colon and rectal cancer with somatic alterations in PI3K pathway genes and randomly assigned them to 160 mg of aspirin or a matched placebo once daily for 3 years.</p><p>For those patients with <i>PIK3CA</i> hotspot mutations in Exon 9 or 20 (Group A) assigned to an aspirin regimen, the estimated 3-year cumulative incidence of recurrence was almost half that of the patients assigned to a matched placebo (7.7% vs. 14.1%; hazard ratio [HR], 0.41; 95% CI, 0.24–0.98; <i>p</i> = .04).</p><p>The benefit was similar in patients with other moderate- or high-impact somatic variants in <i>PIK3CA</i>, <i>PIK3R1</i>, or <i>PTEN</i> (Group B); the estimated 3-year cumulative incidence of recurrence was 7.7% for those assigned to aspirin but 16.8% for those assigned to a placebo (HR, 0.42; 95% CI, 0.21–0.83).</p><p>Subgroup analyses showed an effect of aspirin in patients who had received neoadjuvant therapy, adjuvant therapy, both, or neither and revealed a larger effect of aspirin among female patients versus male patients.</p><p>The safety data reflected what is already known about low-dose aspirin according to the researchers. Severe adverse events occurred in 16.8% of the patients assigned to aspirin and in 11.6% of the patients assigned to a placebo. These severe adverse events commonly included postoperative complications, deep-vein thrombosis, embolism, and infection. Four deaths occurred, with one considered to be potentially related to aspirin use.</p><p>“It is not a standard of care to order next-generation sequencing for <i>PIK3CA</i> in early-stage disease,” says Cathy Eng, MD, FACP, the David H. Johnson Endowed Chair in Surgical and Medical Oncology at the Vanderbilt–Ingram Cancer Center in Nashville, Tennessee, “but more patients are asking for it, and I think it should be considered a standard if diagnosed with early-stage disease.”</p><p>In addition to results from ALASCCA, Dr Eng points out the SAKK 41/13 trial, which was underpowered because of early closure. It also supported the use of aspirin, as it demonstrated improved disease-free survival in favor of 100 mg of aspirin for 3 years in patients with stage II/III colon cancer (HR, 0.57).<span><sup>2</sup></span></p><p>Not all patients with <i>PIK3CA</i> mutations will qualify for use of low-dose aspirin, Dr Eng says. For example, low-dose aspirin should not be recommended for patients with a history of gastrointestinal bleeding, those with recent traumatic
根据ALASCCA试验的结果，与安慰剂相比，每日一次低剂量阿司匹林显著降低了PIK3CA外显子9或20热点突变患者3年结直肠癌复发的累积发生率，对于PI3K途径中其他体细胞改变的患者也有类似的益处。anna Martling，医学博士，瑞典斯德哥尔摩卡罗林斯卡学院的外科教授，和她的同事确定了1103例PI3K通路基因体细胞改变的I-III期结肠癌和直肠癌患者，并将他们随机分配到160毫克阿司匹林或匹配的安慰剂，每天一次，持续3年。对于那些具有PIK3CA外显子9或20热点突变的患者（A组），分配给阿司匹林方案，估计的3年累积复发率几乎是分配给匹配安慰剂的患者的一半（7.7% vs. 14.1%；风险比[HR]， 0.41; 95% CI, 0.24-0.98; p = 0.04）。在PIK3CA、PIK3R1或PTEN中其他中度或高影响体细胞变异的患者中，获益相似（B组）；阿司匹林组3年累积复发率为7.7%，安慰剂组为16.8% （HR, 0.42; 95% CI, 0.21-0.83）。亚组分析显示阿司匹林对接受新辅助治疗、辅助治疗、同时接受辅助治疗或不接受辅助治疗的患者的影响，并显示阿司匹林对女性患者的影响大于男性患者。研究人员表示，安全性数据反映了人们对低剂量阿司匹林的已知认识。严重不良事件发生在16.8%的阿司匹林组患者和11.6%的安慰剂组患者中。这些严重的不良事件通常包括术后并发症、深静脉血栓形成、栓塞和感染。发生了4例死亡，其中1例被认为可能与阿司匹林的使用有关。“在早期疾病中订购PIK3CA的下一代测序并不是标准的护理，”Cathy Eng，医学博士，FACP，田纳西州纳什维尔范德比尔特-英格拉姆癌症中心的大卫·h·约翰逊外科和内科肿瘤学教授说，“但越来越多的患者要求它，我认为如果诊断为早期疾病，它应该被视为标准。”除了ALASCCA的结果外，Eng博士还指出了SAKK 41/13试验，由于过早结束，该试验的动力不足。它也支持阿司匹林的使用，因为它表明，在II/III期结肠癌患者中，服用100 mg阿司匹林3年可提高无病生存期（HR, 0.57）。Eng博士说，并非所有PIK3CA突变患者都有资格使用低剂量阿司匹林。例如，低剂量阿司匹林不应推荐给有胃肠道出血史的患者、最近有创伤性头部创伤的患者或有出血性疾病的患者。“然而，我认为这些数据非常有趣，在遇到早期患者时应该考虑到这一点，”Eng博士说。“我已经开始与我所有的病人讨论这些结果，以及使用阿司匹林作为辅助治疗范例的一部分可能带来的好处。”
{"title":"Aspirin use reduced recurrence in a molecularly defined subgroup of patients with CRC","authors":"Leah Lawrence","doi":"10.1002/cncr.70208","DOIUrl":"10.1002/cncr.70208","url":null,"abstract":"<p>Once daily low-dose aspirin significantly reduced the cumulative incidence of colorectal cancer recurrence at 3 years in comparison with a placebo in patients with <i>PIK3CA</i> hotspot mutations in Exon 9 or 20, with a similar benefit found for patients with other somatic alterations in the PI3K pathway, according to results of the ALASCCA trial.<span><sup>1</sup></span></p><p>Anna Martling, MD, PhD, a professor of surgery at the Karolinska Institutet in Stockholm, Sweden, and her colleagues identified 1103 patients with stage I–III colon and rectal cancer with somatic alterations in PI3K pathway genes and randomly assigned them to 160 mg of aspirin or a matched placebo once daily for 3 years.</p><p>For those patients with <i>PIK3CA</i> hotspot mutations in Exon 9 or 20 (Group A) assigned to an aspirin regimen, the estimated 3-year cumulative incidence of recurrence was almost half that of the patients assigned to a matched placebo (7.7% vs. 14.1%; hazard ratio [HR], 0.41; 95% CI, 0.24–0.98; <i>p</i> = .04).</p><p>The benefit was similar in patients with other moderate- or high-impact somatic variants in <i>PIK3CA</i>, <i>PIK3R1</i>, or <i>PTEN</i> (Group B); the estimated 3-year cumulative incidence of recurrence was 7.7% for those assigned to aspirin but 16.8% for those assigned to a placebo (HR, 0.42; 95% CI, 0.21–0.83).</p><p>Subgroup analyses showed an effect of aspirin in patients who had received neoadjuvant therapy, adjuvant therapy, both, or neither and revealed a larger effect of aspirin among female patients versus male patients.</p><p>The safety data reflected what is already known about low-dose aspirin according to the researchers. Severe adverse events occurred in 16.8% of the patients assigned to aspirin and in 11.6% of the patients assigned to a placebo. These severe adverse events commonly included postoperative complications, deep-vein thrombosis, embolism, and infection. Four deaths occurred, with one considered to be potentially related to aspirin use.</p><p>“It is not a standard of care to order next-generation sequencing for <i>PIK3CA</i> in early-stage disease,” says Cathy Eng, MD, FACP, the David H. Johnson Endowed Chair in Surgical and Medical Oncology at the Vanderbilt–Ingram Cancer Center in Nashville, Tennessee, “but more patients are asking for it, and I think it should be considered a standard if diagnosed with early-stage disease.”</p><p>In addition to results from ALASCCA, Dr Eng points out the SAKK 41/13 trial, which was underpowered because of early closure. It also supported the use of aspirin, as it demonstrated improved disease-free survival in favor of 100 mg of aspirin for 3 years in patients with stage II/III colon cancer (HR, 0.57).<span><sup>2</sup></span></p><p>Not all patients with <i>PIK3CA</i> mutations will qualify for use of low-dose aspirin, Dr Eng says. For example, low-dose aspirin should not be recommended for patients with a history of gastrointestinal bleeding, those with recent traumatic","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.70208","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008151","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}
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}
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