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Treatment adaptation based on response to induction chemotherapy in nasopharyngeal carcinoma: An evolving landscape
IF 254.7 1区 医学 Q1 ONCOLOGY Pub Date : 2025-03-20 DOI: 10.3322/caac.70004
Nadia A. Saeed, Annie W. Chan
<p>Patients with nasopharyngeal carcinoma (NPC) represent a distinct group with head and neck cancer. They are often nontobacco users, nonalcohol users, and on average are 10 to 20 years younger than patients with cancers of other head and neck sites. Given good baseline health status and the effectiveness of contemporary treatment,<span><sup>1-3</sup></span> patients with NPC typically have long projected life expectancies and commonly develop late treatment effects, such as cranial nerve deficits and dysphagia. Previous efforts in reducing radiation-related toxicity included the use of reduced target doses<span><sup>4</sup></span> and volumes.<span><sup>3, 5-8</sup></span></p><p>In this issue of <i>CA: A Cancer Journal for Clinicians</i>, Tang et al. report the results of their multicenter phase 3 trial of 445 patients with locoregionally advanced NPC, in which patients were randomized to receive either reduced-volume radiotherapy based on the postinduction chemotherapy (post-IC) gross tumor volume (GTV) or standard radiotherapy based on the preinduction (pre-IC) chemotherapy GTV.<span><sup>9</sup></span> The primary end point was locoregional relapse-free survival at 3 years, with a noninferiority margin of 8%. Overall survival, distant metastasis-free survival, failure-free survival, adverse events, and quality of life (QoL) were also reported as secondary end points. The study is well designed, has a large patient cohort, and provides high-quality data exploring this essential question. With a median follow-up of 40.4 months, patients in the post-IC arm had noninferiority in locoregional relapse-free and overall survival as well as lower toxicities and improved QoL compared with patients in the pre-IC arm. This study has important implications for the future of tailored radiotherapy in NPC. Long-term follow-up, however, is necessary to confirm the findings.</p><p>The findings of Tang et al. shared similarities with those of another recently published randomized trial.<span><sup>8</sup></span> In that multicenter trial of 212 patients with stage III–VB, locally advanced NPC, the authors demonstrated that treating the post-IC GTV resulted in noninferior locoregional relapse compared with treating the pre-IC GTV, with potentially improved QoL and less late toxicity. Different chemotherapy regimens and schedules were used in the study. Given the results of these two randomized trials demonstrating noninferiority in both locoregional relapse and survival with this de-intensification approach, should the use of the post-IC GTV for intensity-modulated radiotherapy planning be adopted universally? Before we make a conclusion, let us first examine some fundamental questions in NPC treatment.</p><p>First, does chemosensitivity equate with radiosensitivity? In these studies, the determination for radiosensitivity was based on chemosensitivity. It is important to recognize that chemosensitivity does not necessarily correlate with radiosensitivity. Th
{"title":"Treatment adaptation based on response to induction chemotherapy in nasopharyngeal carcinoma: An evolving landscape","authors":"Nadia A. Saeed, Annie W. Chan","doi":"10.3322/caac.70004","DOIUrl":"https://doi.org/10.3322/caac.70004","url":null,"abstract":"&lt;p&gt;Patients with nasopharyngeal carcinoma (NPC) represent a distinct group with head and neck cancer. They are often nontobacco users, nonalcohol users, and on average are 10 to 20 years younger than patients with cancers of other head and neck sites. Given good baseline health status and the effectiveness of contemporary treatment,&lt;span&gt;&lt;sup&gt;1-3&lt;/sup&gt;&lt;/span&gt; patients with NPC typically have long projected life expectancies and commonly develop late treatment effects, such as cranial nerve deficits and dysphagia. Previous efforts in reducing radiation-related toxicity included the use of reduced target doses&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; and volumes.&lt;span&gt;&lt;sup&gt;3, 5-8&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;\u0000&lt;p&gt;In this issue of &lt;i&gt;CA: A Cancer Journal for Clinicians&lt;/i&gt;, Tang et al. report the results of their multicenter phase 3 trial of 445 patients with locoregionally advanced NPC, in which patients were randomized to receive either reduced-volume radiotherapy based on the postinduction chemotherapy (post-IC) gross tumor volume (GTV) or standard radiotherapy based on the preinduction (pre-IC) chemotherapy GTV.&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; The primary end point was locoregional relapse-free survival at 3 years, with a noninferiority margin of 8%. Overall survival, distant metastasis-free survival, failure-free survival, adverse events, and quality of life (QoL) were also reported as secondary end points. The study is well designed, has a large patient cohort, and provides high-quality data exploring this essential question. With a median follow-up of 40.4 months, patients in the post-IC arm had noninferiority in locoregional relapse-free and overall survival as well as lower toxicities and improved QoL compared with patients in the pre-IC arm. This study has important implications for the future of tailored radiotherapy in NPC. Long-term follow-up, however, is necessary to confirm the findings.&lt;/p&gt;\u0000&lt;p&gt;The findings of Tang et al. shared similarities with those of another recently published randomized trial.&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; In that multicenter trial of 212 patients with stage III–VB, locally advanced NPC, the authors demonstrated that treating the post-IC GTV resulted in noninferior locoregional relapse compared with treating the pre-IC GTV, with potentially improved QoL and less late toxicity. Different chemotherapy regimens and schedules were used in the study. Given the results of these two randomized trials demonstrating noninferiority in both locoregional relapse and survival with this de-intensification approach, should the use of the post-IC GTV for intensity-modulated radiotherapy planning be adopted universally? Before we make a conclusion, let us first examine some fundamental questions in NPC treatment.&lt;/p&gt;\u0000&lt;p&gt;First, does chemosensitivity equate with radiosensitivity? In these studies, the determination for radiosensitivity was based on chemosensitivity. It is important to recognize that chemosensitivity does not necessarily correlate with radiosensitivity. Th","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"20 1","pages":""},"PeriodicalIF":254.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Defeating lethal cancer: Interrupting the ecologic and evolutionary basis of death from malignancy
IF 254.7 1区 医学 Q1 ONCOLOGY Pub Date : 2025-03-09 DOI: 10.3322/caac.70000
Kenneth J. Pienta, Patrick L. Goodin, Sarah R. Amend
Despite the advances in cancer prevention, early detection, and treatments, all of which have led to improved cancer survival, globally, there is an increased incidence in cancer-related deaths. Although each patient and each tumor is wholly unique, the tipping point to incurable disease is common across all patients: the dual capacity for cancers to metastasize and resist systemic treatment. The discovery of genetic mutations and epigenetic variation that emerges during cancer progression highlights that evolutionary and ecology principles can be used to understand how cancer evolves to a lethal phenotype. By applying such an eco-evolutionary framework, the authors reinterpret our understanding of the metastatic process as one of an ecologic invasion and define the eco-evolutionary paths of evolving therapy resistance. With this understanding, the authors draw from successful strategies optimized in evolutionary ecology to define strategic interventions with the goal of altering the evolutionary trajectory of lethal cancer. Ultimately, studying, understanding, and treating cancer using evolutionary ecology principles provides an opportunity to improve the lives of patients with cancer.
{"title":"Defeating lethal cancer: Interrupting the ecologic and evolutionary basis of death from malignancy","authors":"Kenneth J. Pienta, Patrick L. Goodin, Sarah R. Amend","doi":"10.3322/caac.70000","DOIUrl":"https://doi.org/10.3322/caac.70000","url":null,"abstract":"Despite the advances in cancer prevention, early detection, and treatments, all of which have led to improved cancer survival, globally, there is an increased incidence in cancer-related deaths. Although each patient and each tumor is wholly unique, the tipping point to incurable disease is common across all patients: the dual capacity for cancers to metastasize and resist systemic treatment. The discovery of genetic mutations and epigenetic variation that emerges during cancer progression highlights that evolutionary and ecology principles can be used to understand how cancer evolves to a lethal phenotype. By applying such an eco-evolutionary framework, the authors reinterpret our understanding of the metastatic process as one of an ecologic invasion and define the eco-evolutionary paths of evolving therapy resistance. With this understanding, the authors draw from successful strategies optimized in evolutionary ecology to define strategic interventions with the goal of altering the evolutionary trajectory of lethal cancer. Ultimately, studying, understanding, and treating cancer using evolutionary ecology principles provides an opportunity to improve the lives of patients with cancer.","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"54 1","pages":""},"PeriodicalIF":254.7,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143576106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cancer statistics for African American and Black people, 2025.
IF 503.1 1区 医学 Q1 ONCOLOGY Pub Date : 2025-02-20 DOI: 10.3322/caac.21874
Anatu H Saka, Angela N Giaquinto, Lauren E McCullough, Katherine Y Tossas, Jessica Star, Ahmedin Jemal, Rebecca L Siegel

African American and other Black individuals (referred to as Black people in this article) have a disproportionate cancer burden, including the lowest survival of any racial or ethnic group for most cancers. Every 3 years, the American Cancer Society estimates the number of new cancer cases and deaths for Black people in the United States and compiles the most recent data on cancer incidence (herein through 2021), mortality (through 2022), survival, screening, and risk factors using population-based data from the National Cancer Institute and the Centers for Disease Control and Prevention. In 2025, there will be approximately 248,470 new cancer cases and 73,240 cancer deaths among Black people in the United States. Black men have experienced the largest relative decline in cancer mortality from 1991 to 2022 overall (49%) and in almost every 10-year age group, by as much as 65%-67% in the group aged 40-59 years. This progress largely reflects historical reductions in smoking initiation among Black teens, advances in treatment, and earlier detections for some cancers. Nevertheless, during the most recent 5 years, Black men had 16% higher mortality than White men despite just 4% higher incidence, and Black women had 10% higher mortality than White women despite 9% lower incidence. Larger inequalities for mortality than for incidence reflect two-fold higher death rates for prostate, uterine corpus, and stomach cancers and for myeloma, and 40%-50% higher rates for colorectal, breast, cervical, and liver cancers. The causes of ongoing disparities are multifactorial, but largely stem from inequalities in the social determinants of health that trace back to structural racism. Increasing diversity in clinical trials, enhancing provider education, and implementing financial incentives to ensure equitable care across the cancer care continuum would help close these gaps.

{"title":"Cancer statistics for African American and Black people, 2025.","authors":"Anatu H Saka, Angela N Giaquinto, Lauren E McCullough, Katherine Y Tossas, Jessica Star, Ahmedin Jemal, Rebecca L Siegel","doi":"10.3322/caac.21874","DOIUrl":"https://doi.org/10.3322/caac.21874","url":null,"abstract":"<p><p>African American and other Black individuals (referred to as Black people in this article) have a disproportionate cancer burden, including the lowest survival of any racial or ethnic group for most cancers. Every 3 years, the American Cancer Society estimates the number of new cancer cases and deaths for Black people in the United States and compiles the most recent data on cancer incidence (herein through 2021), mortality (through 2022), survival, screening, and risk factors using population-based data from the National Cancer Institute and the Centers for Disease Control and Prevention. In 2025, there will be approximately 248,470 new cancer cases and 73,240 cancer deaths among Black people in the United States. Black men have experienced the largest relative decline in cancer mortality from 1991 to 2022 overall (49%) and in almost every 10-year age group, by as much as 65%-67% in the group aged 40-59 years. This progress largely reflects historical reductions in smoking initiation among Black teens, advances in treatment, and earlier detections for some cancers. Nevertheless, during the most recent 5 years, Black men had 16% higher mortality than White men despite just 4% higher incidence, and Black women had 10% higher mortality than White women despite 9% lower incidence. Larger inequalities for mortality than for incidence reflect two-fold higher death rates for prostate, uterine corpus, and stomach cancers and for myeloma, and 40%-50% higher rates for colorectal, breast, cervical, and liver cancers. The causes of ongoing disparities are multifactorial, but largely stem from inequalities in the social determinants of health that trace back to structural racism. Increasing diversity in clinical trials, enhancing provider education, and implementing financial incentives to ensure equitable care across the cancer care continuum would help close these gaps.</p>","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":" ","pages":""},"PeriodicalIF":503.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reduced-volume radiotherapy versus conventional-volume radiotherapy after induction chemotherapy in nasopharyngeal carcinoma: An open-label, noninferiority, multicenter, randomized phase 3 trial.
IF 503.1 1区 医学 Q1 ONCOLOGY Pub Date : 2025-02-19 DOI: 10.3322/caac.21881
Ling-Long Tang, Lin Chen, Gui-Qiong Xu, Ning Zhang, Cheng-Long Huang, Wen-Fei Li, Yan-Ping Mao, Guan-Qun Zhou, Feng Lei, Lu-Si Chen, Shao Hui Huang, Lei Chen, Yu-Pei Chen, Yuan Zhang, Xu Liu, Cheng Xu, Yin Zhao, Ji-Bin Li, Na Liu, Fang-Yun Xie, Rui Guo, Ying Sun, Jun Ma

Background: Nearly 90% locoregionally advanced nasopharyngeal carcinoma (LANPC) responds to induction chemotherapy (IC) with significant tumor volume shrinkage. Radiotherapy always follows IC, and reduced volume has been proposed. However, the efficacy and safety of reduced-volume radiotherapy is uncertain.

Methods: In this multi-center, noninferiority, randomized, controlled trial, patients with LANPC who completed IC were randomly assigned (1:1) to receive reduced-volume radiotherapy based on post-IC tumor volume (Post-IC group) or conventional volume radiotherapy based on pre-IC tumor volume (Pre-IC group). The primary endpoint was locoregional relapse-free survival, with a noninferiority margin of 8%. Secondary endpoints comprised adverse events, and quality of life (QoL).

Results: Between August 7, 2020, and May 27, 2022, 445 patients were randomly assigned to Post-IC (n = 225) or Pre-IC (n = 220) groups. The average volume receiving radical dose was 66.6 cm3 in Post-IC group versus 80.9 cm3. After a median follow-up of 40.4 months, the 3-year locoregional relapse-free survival was 91.5% in the Post-IC group versus 91.2%, with a difference of 0.3% (95% confidence interval -4.9% to 5.5%). The incidence of grade 3-4 radiation-related toxicity was lower in the Post-IC group including: acute mucositis (19.8% vs 34.1%), late otitis media (9.5% vs 20.9%) and late dry month (3.6% vs 9.5%). The Post-IC group had better QoL for global health status, physical functioning, emotional functioning, dry mouth and sticky saliva.

Conclusions: In this trial, reduced-volume radiotherapy was noninferior to conventional volume radiotherapy in locoregional relapse-free survival, and was associated with lower toxicities and improved QoL. (ClinicalTrials.gov identifier NCT04384627).

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引用次数: 0
Novel clinical trial designs emerging from the molecular reclassification of cancer 新的临床试验设计从癌症的分子重新分类出现
IF 254.7 1区 医学 Q1 ONCOLOGY Pub Date : 2025-01-22 DOI: 10.3322/caac.21880
Mina Nikanjam, Shumei Kato, Teresa Allen, Jason K. Sicklick, Razelle Kurzrock
Next-generation sequencing has revealed the disruptive reality that advanced/metastatic cancers have complex and individually distinct genomic landscapes, necessitating a rethinking of treatment strategies and clinical trial designs. Indeed, the molecular reclassification of cancer suggests that it is the molecular underpinnings of the disease, rather than the tissue of origin, that mostly drives outcomes. Consequently, oncology clinical trials have evolved from standard phase 1, 2, and 3 tissue-specific studies; to tissue-specific, biomarker-driven trials; to tissue-agnostic trials untethered from histology (all drug-centered designs); and, ultimately, to patient-centered, N-of-1 precision medicine studies in which each patient receives a personalized, biomarker-matched therapy/combination of drugs. Innovative technologies beyond genomics, including those that address transcriptomics, immunomics, proteomics, functional impact, epigenetic changes, and metabolomics, are enabling further refinement and customization of therapy. Decentralized studies have the potential to improve access to trials and precision medicine approaches for underserved minorities. Evaluation of real-world data, assessment of patient-reported outcomes, use of registry protocols, interrogation of exceptional responders, and exploitation of synthetic arms have all contributed to personalized therapeutic approaches. With greater than 1 × 1012 potential patterns of genomic alterations and greater than 4.5 million possible three-drug combinations, the deployment of artificial intelligence/machine learning may be necessary for the optimization of individual therapy and, in the near future, also may permit the discovery of new treatments in real time.
新一代测序揭示了一个颠覆性的现实,即晚期/转移性癌症具有复杂且个体不同的基因组景观,需要重新思考治疗策略和临床试验设计。事实上,癌症的分子重新分类表明,主要是疾病的分子基础,而不是起源组织,驱动了结果。因此,肿瘤临床试验已经从标准的1、2和3期组织特异性研究发展;组织特异性、生物标志物驱动的试验;不受组织学限制的组织不可知试验(所有以药物为中心的设计);最终,以患者为中心,N-of-1的精准医学研究,每个患者接受个性化的、生物标志物匹配的治疗/药物组合。基因组学之外的创新技术,包括转录组学、免疫组学、蛋白质组学、功能影响、表观遗传变化和代谢组学,正在进一步完善和定制治疗。分散的研究有可能改善服务不足的少数群体获得试验和精确医疗方法的机会。对真实世界数据的评估、对患者报告结果的评估、注册方案的使用、对特殊应答者的询问以及合成武器的利用都有助于个性化治疗方法。有超过1 × 1012种潜在的基因组改变模式和超过450万种可能的三种药物组合,人工智能/机器学习的部署对于优化个体治疗可能是必要的,并且在不久的将来,也可能允许实时发现新的治疗方法。
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引用次数: 0
Erectile dysfunction common within the first year after rectal cancer surgery 勃起功能障碍常见于直肠癌手术后的第一年
IF 503.1 1区 医学 Q1 ONCOLOGY Pub Date : 2025-01-20 DOI: 10.3322/caac.21879
Mike Fillon
<p>Colorectal cancer studies commonly use broad “umbrella” terms when discussing the outcomes of rectal cancer surgery and fail to ferret out the prevalence of the individual side effects. A study from Denmark has investigated the prevalence of erectile dysfunction (ED) 1 year after rectal cancer surgery, especially because survival rates for patients with rectal cancer have increased substantially on account of improvements in surgical, oncological, perioperative, and chemotherapy care.</p><p>However, this also has led to a growing risk of postsurgical complications, noted the study authors. For example, resection of the rectum can cause intraoperative nerve damage to the pelvic plexus nerves, which is believed to be the leading cause of postoperative sexual dysfunction.</p><p>The study appears in the <i>European Journal of Surgical Oncology</i> (doi:10.1016/j.ejso.2024.108662).</p><p>According to the lead study author, Sebastian B. Hansen, PhD, who works at the Center for Perioperative Optimization in the Department of Surgery at the Copenhagen University Hospital in Denmark, the primary objective of this systematic review was to estimate the prevalence of ED within the first year after surgery for rectal cancer.</p><p>The second objective, Dr Hansen says, was to assess to what extent the surgical approach and techniques, including chemotherapy and radiotherapy, affected the occurrence of ED. “We wanted to investigate if the risk of developing sexual dysfunction following rectal cancer treatment was substantial, and if so, what contributed to it.” He adds that they were aware that the disease itself might contribute to the risk of sexual function impairment.</p><p>The researchers believe that their data overall are valid, even though the prevalence of moderate to severe ED varied between different studies. As a result, they are confident that “a great number of recovering rectal cancer patients are at risk.”</p><p>The overall confidence levels were low because even though the initial search resulted in 74 studies, only 22 studies were included in the analysis, as noted previously. The researchers wrote that this was due to “shortcomings” in the data reporting. For example, they noted that even though most of the studies used the 5- and 15-item versions of the International Index of Erectile Function, which allows for the stratification of ED degrees on a point score, the bulk of the studies reported only the mean or median results. They believe that this minimized their ability to gauge the level and intensity of ED. “The degree of ED is important since rectal cancer usually affects older men who (already) might have some deterioration in ED function at the time of diagnosis (and not an after effect from surgery),” they said.</p><p>Another key finding from the study was that overall, no significant difference was found with respect to the time of follow-up during the first year. However, the researchers speculate that a reason for the lower inc
“这些信息可能不会导致决策的改变,但可能有助于长期癌症幸存者的计划和治疗。”-Robert Krouse, md结直肠癌研究在讨论直肠癌手术的结果时通常使用宽泛的“总括性”术语,而无法找出个体副作用的普遍性。丹麦的一项研究调查了直肠癌手术后1年勃起功能障碍(ED)的患病率,特别是因为直肠癌患者的生存率由于手术、肿瘤、围手术期和化疗护理的改善而大幅增加。然而,该研究的作者指出,这也导致了术后并发症的风险增加。例如,切除直肠可引起术中盆腔丛神经损伤,这被认为是术后性功能障碍的主要原因。这项研究发表在欧洲外科肿瘤学杂志上(doi:10.1016/ j.j ejso.2024.108662)。
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引用次数: 0
Inhibiting monoclonal antibody GDF-15 improves cancer cachexia symptoms 抑制单克隆抗体GDF-15改善癌症恶病质症状
IF 503.1 1区 医学 Q1 ONCOLOGY Pub Date : 2025-01-20 DOI: 10.3322/caac.21878
Mike Fillon
<p>A new phase 2 study found that ponsegromab (Pfizer) helped with issues typically associated with cancer cachexia by suppressing weight loss and improving appetite and physical activity. Researchers found that the monoclonal antibody inhibited the serum level of growth differentiation factor 15 (GDF-15), which is associated with cachexia’s multifaceted syndrome. Currently, there are no medicines approved for treating cancer cachexia.</p><p>“We believe this study is a unique development elevating symptom science because it is a biomarker-driven symptom intervention,” says study author Eric Roeland, MD, an associate professor of medicine in the Division of Hematology/Medical Oncology at the Oregon Health and Science University’s Knight Cancer Institute Clinic in Portland, Oregon.</p><p>The study appears in <i>The New England Journal of Medicine</i> (doi:10.1056/NEJMoa2409515).</p><p>This first in-patient, open-label, phase 1b study assessed the use of ponsegromab in 10 patients with cancer cachexia and elevated GDF-15 serum concentrations. Researchers found that ponsegromab improved the patients’ body weight and appetite, with lower serum GDF-15 levels and few adverse events (doi:10.1158/1078-0432.CCR-23-1631).</p><p>Dr Roeland says that a key reason for this latest study was the recognition that the GDF-15 cytokine binds to the glial cell–derived neurotrophic factor family receptor alpha-like protein (GFRAL) in the hindbrain. The GDF–GFRAL pathway is recognized as a main modulator of anorexia and body-weight regulation that potentially results in cachexia. These reported results are included in Part A of the study; Part B, an optional open-label extension, is ongoing.</p><p>The study was conducted from February through December 2023 with 187 patients: 40% had non–small cell lung cancer (74 patients), 32% had pancreatic cancer (59 patients), and 29% had colorectal cancer (54 patients). Patients were at least 18 years old with a median age of 67 years. Approximately two thirds of the participants were male; 37% of the participants were female.</p><p>The potential cachexia symptoms that the researchers investigated included a non–diet-related weight loss of 5% or more in the prior 6 months and an elevated serum GDF-15 level (≥1500 pg/mL). Patients with cachexia due to a nonmalignant illness, planned surgery, or weight-gaining prescribed drugs were excluded.</p><p>Ponsegromab was administered to patients at 74 sites in 11 countries. Four similarly sized groups underwent randomization. Every 4 weeks, one group (46 patients) received 100 mg subcutaneously, the second group (46 patients) received 200 mg subcutaneously, the third group (50 patients) received 400 mg subcutaneously, and 45 patients received a placebo, for a total of three doses each.</p><p>All 187 patients were treated, with 137 patients (73%) completing the 12-week trial. A similar number of patients in each group did not complete the study.</p><p>The primary end point was weight variati
一项新的2期研究发现,ponsegromab(辉瑞)通过抑制体重下降、改善食欲和身体活动,帮助解决与癌症恶病质相关的问题。研究人员发现,单克隆抗体抑制了与恶病质多面综合征相关的血清生长分化因子15 (GDF-15)水平。目前,还没有药物被批准用于治疗癌症恶病质。“我们相信这项研究是一个提升症状科学的独特发展,因为它是一种生物标志物驱动的症状干预,”研究作者Eric Roeland医学博士说,他是俄勒冈州波特兰市俄勒冈健康与科学大学奈特癌症研究所诊所血液学/医学肿瘤学部门的医学副教授。这项研究发表在《新英格兰医学杂志》上(doi:10.1056/NEJMoa2409515)。
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引用次数: 0
Cancer statistics, 2025: A hinge moment for optimism to morph into hope? 癌症统计,2025年:乐观转变为希望的关键时刻?
IF 503.1 1区 医学 Q1 ONCOLOGY Pub Date : 2025-01-16 DOI: 10.3322/caac.21877
Benjamin W. Corn MD, David B. Feldman PhD
<p>Since 1951, the American Cancer Society has compiled and published data on an annual basis pertaining to the incidence and outcomes of most malignancies in the United States. This meticulous effort consistently manifests as one of the most cited articles in the literature, extensively referenced not only by oncologists but also by health scientists at large. The influence of this reporting is attributable to its comprehensiveness, readability, and the establishment of benchmarks for where we are, where we have been, and where we ought to be headed.</p><p>This year's article by Siegel et al.,<span><sup>1</sup></span> once again, provides important insights. Five-year relative all-cancer survival rates increased from 49% between 1975 and 1977 to approximately 69% between 2014 and 2020. Moreover, the general cancer mortality rate continues to fall. However, closer scrutiny reveals dramatic disparities. For instance, overall cancer incidence has declined in men but has been persistently rising in women. In addition, disproportionate cancer mortality is borne by Native Americans (particularly with regard to primary tumors of the colorectum, kidney, liver, lung, stomach, and uterine cervix), Black men (especially in the setting of prostate cancer), and Black women (for breast and uterine corpus cancers). Driving these disparities, Siegel et al. point to socioeconomic deprivation resulting from structural racism, including (but not limited to) inequities in access to screening and treatment.</p><p>The authors assert identifiable factors linked to other statistical trends as well. Although some of the apparent spikes in cancer burden may be attributable to a return to previous levels of screening and incidental detection after a dip in provider visits because of the coronavirus disease 2019 pandemic, simultaneously, there is concern about the growing popularity of electronic cigarettes and vaping. Meanwhile, although there has been an increase in overall cancer incidence among women, it is encouraging to learn that national human papillomavirus vaccination programs have gained traction and—when conjoined with punctilious screening as well as aggressive treatment of precursor lesions—have reduced the incidence of cervical cancer in people with a cervix. Furthermore, Siegel and colleagues comment on the association between increased research funding and improved rates of survival for hematopoietic and lymphoid malignancies. This contrasts with the underfunding of research regarding uterine corpus cancer, the only malignancy for which survival has steadfastly decreased during the past 4 decades.</p><p>Given the increased relative cancer survival rate, it is not uncommon for oncologists and the general public to express optimism. There is a theme that emerges from these numbers building on the prior reports of recent years: most cancers are potentially controllable, provided there is appropriate investment of research dollars, sufficient screening, and ac
但对于许多癌症患者来说,这种强烈的不可控性可能已不再适用。虽然癌症显然仍有许多不可控因素,但在过去的 30 年中,癌症的结果比以前更容易控制。6 事实上,沙纳汉(Shanahan)等人7 发现,在可控的情况下,希望能预测具体的预期,而在不可控的情况下,乐观则更能预测。甚至有迹象表明,希望水平较高的患者与希望水平较低的患者相比,其癌症预后会有所改善。8 当情况的可控性较高时--尤其是在面对癌症这样一个具有挑战性的敌人时--设定目标、规划路径和唤起代入感的能力就变得至关重要。作为一个重要的旁观者,尽管治愈是一个值得追求的目标,但我们提醒不要将癌症患者的愿望局限于治愈这一单一目标。身体健康的人怀有许多希望,没有理由认为癌症患者会有什么不同。即使在西格尔等人确定的不可能治愈的亚人群中,也可以采用希望理论来追求广泛的目标,包括症状缓解以及一系列非医疗目标,这些都是我们珍视的人性本质。9 通过使用这些工具,我们和其他人10-12 已经证明,可以开展简单的工作坊来帮助个人--包括病人和照护者--掌握技能,帮助他们变得更有希望。事实上,医生和其他医疗保健专业人士都表示,学习如何利用希望理论中的工具是有价值的。13 在肿瘤环境中,这些工具也许比以往任何时候都更有意义,因为肿瘤环境提供了更大的可控性,这要归功于充满希望的发展,如创新且有效的疗法的出现、14 证明早期检测项目价值的长期随访15 以及对坚持这些理念的价值达成的共识16。16 然而,如前所述,癌症确诊后的治疗效果,包括整个癌症治疗过程中的创新,并没有得到公平分配,这就造成了明显的差距和社会公正问题。这也可能造成希望的落差。对于许多边缘化群体来说,过去的经历和结构性障碍,包括获得优质医疗服务的机会有限,可能会降低甚至消除他们找到希望的能力。17-19 这可能会对现实世界产生影响;例如,有新的证据表明,在各种医疗条件下,希望与坚持治疗有关。20, 21 作为社会,我们必须努力承认并纠正这些差异,我们的医疗保健系统必须继续解决导致希望减少并最终导致结果的潜在不平等。换句话说,"保持希望 "不仅仅是病人的任务,为他们提供这样做的理由也是医疗行业的责任。随着癌症越来越成为一种可控疾病,希望--而不是乐观--成为了更相关的心理结构。但事实上,并非所有患者都能抱有这种希望,这表明我们需要继续开展研究和积极行动。重要的是,希望是一种动态现象,而非静态现象--它促使我们设定目标,寻找通往美好未来的奋斗途径,并问自己:"我们现在该怎么办?"
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引用次数: 0
Cancer statistics, 2025 癌症统计,2025年
IF 503.1 1区 医学 Q1 ONCOLOGY Pub Date : 2025-01-16 DOI: 10.3322/caac.21871
Rebecca L. Siegel MPH, Tyler B. Kratzer MPH, Angela N. Giaquinto MSPH, Hyuna Sung PhD, Ahmedin Jemal DVM, PhD

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes using incidence data collected by central cancer registries (through 2021) and mortality data collected by the National Center for Health Statistics (through 2022). In 2025, 2,041,910 new cancer cases and 618,120 cancer deaths are projected to occur in the United States. The cancer mortality rate continued to decline through 2022, averting nearly 4.5 million deaths since 1991 because of smoking reductions, earlier detection for some cancers, and improved treatment. Yet alarming disparities persist; Native American people bear the highest cancer mortality, including rates that are two to three times those in White people for kidney, liver, stomach, and cervical cancers. Similarly, Black people have two-fold higher mortality than White people for prostate, stomach, and uterine corpus cancers. Overall cancer incidence has generally declined in men but has risen in women, narrowing the male-to-female rate ratio (RR) from a peak of 1.6 (95% confidence interval, 1.57–1.61) in 1992 to 1.1 (95% confidence interval, 1.12–1.12) in 2021. However, rates in women aged 50–64 years have already surpassed those in men (832.5 vs. 830.6 per 100,000), and younger women (younger than 50 years) have an 82% higher incidence rate than their male counterparts (141.1 vs. 77.4 per 100,000), up from 51% in 2002. Notably, lung cancer incidence in women surpassed that in men among people younger than 65 years in 2021 (15.7 vs. 15.4 per 100,000; RR, 0.98, p = 0.03). In summary, cancer mortality continues to decline, but future gains are threatened by rampant racial inequalities and a growing burden of disease in middle-aged and young adults, especially women. Continued progress will require investment in cancer prevention and access to equitable treatment, especially for Native American and Black individuals.

美国癌症协会每年都会估算美国新发癌症病例和死亡人数,并利用中央癌症登记处收集的发病率数据(至 2021 年)和国家卫生统计中心收集的死亡率数据(至 2022 年),汇编最新的人口癌症发生率和结果数据。预计 2025 年美国将新增癌症病例 2,041,910 例,癌症死亡病例 618,120 例。到 2022 年,癌症死亡率将继续下降,自 1991 年以来,由于减少吸烟、提早发现某些癌症以及改善治疗,已避免近 450 万人死亡。然而,令人震惊的差距依然存在;美国原住民的癌症死亡率最高,其中肾癌、肝癌、胃癌和宫颈癌的死亡率是白人的两到三倍。同样,黑人的前列腺癌、胃癌和子宫癌死亡率是白人的两倍。男性的总体癌症发病率普遍下降,但女性的发病率有所上升,男女发病率比(RR)从 1992 年的峰值 1.6(95% 置信区间,1.57-1.61)缩小到 2021 年的 1.1(95% 置信区间,1.12-1.12)。然而,50-64 岁女性的发病率已经超过了男性(每 10 万人中有 832.5 人对 830.6 人),年轻女性(50 岁以下)的发病率比男性高出 82%(每 10 万人中有 141.1 人对 77.4 人),比 2002 年的 51% 有所上升。值得注意的是,2021 年,在 65 岁以下人群中,女性肺癌发病率超过男性(每 10 万人中 15.7 例对 15.4 例;RR,0.98,P = 0.03)。总之,癌症死亡率在继续下降,但种族不平等现象严重,中青年尤其是女性的疾病负担日益加重,这些都威胁着未来的进展。要想继续取得进展,就必须在癌症预防和获得公平治疗方面进行投资,尤其是对美国原住民和黑人而言。
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引用次数: 0
A pan-tumor review of the role of poly(adenosine diphosphate ribose) polymerase inhibitors 聚二磷酸腺苷核糖聚合酶抑制剂在泛肿瘤中的作用综述
IF 254.7 1区 医学 Q1 ONCOLOGY Pub Date : 2025-01-10 DOI: 10.3322/caac.21870
Chadi Hage Chehade, Georges Gebrael, Nicolas Sayegh, Zeynep Irem Ozay, Arshit Narang, Tony Crispino, Talia Golan, Jennifer K. Litton, Umang Swami, Kathleen N. Moore, Neeraj Agarwal
Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors, such as olaparib, talazoparib, rucaparib, and niraparib, comprise a therapeutic class that targets PARP proteins involved in DNA repair. Cancer cells with homologous recombination repair defects, particularly BRCA alterations, display enhanced sensitivity to these agents because of synthetic lethality induced by PARP inhibitors. These agents have significantly improved survival outcomes across various malignancies, initially gaining regulatory approval in ovarian cancer and subsequently in breast, pancreatic, and prostate cancers in different indications. This review offers a comprehensive clinical overview of PARP inhibitor approvals, emphasizing their efficacy across different cancers based on landmark phase 3 clinical trials.
聚(腺苷二磷酸核糖)聚合酶(PARP)抑制剂,如奥拉帕尼、塔拉唑帕尼、鲁卡帕尼和尼拉帕尼,包括针对参与DNA修复的PARP蛋白的治疗类。具有同源重组修复缺陷的癌细胞,特别是BRCA突变,由于PARP抑制剂诱导的合成致死性,对这些药物表现出更高的敏感性。这些药物显著改善了各种恶性肿瘤的生存结果,最初在卵巢癌中获得监管批准,随后在不同适应症中用于乳腺癌、胰腺癌和前列腺癌。本综述提供了PARP抑制剂批准的全面临床概述,强调了基于具有里程碑意义的3期临床试验对不同癌症的疗效。
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引用次数: 0
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CA: A Cancer Journal for Clinicians
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