Pub Date : 2025-12-10DOI: 10.1158/1557-3265.earlyonsetca25-b022
Sunyeop Lee, Erica J. Lee Argov, Parisa Tehranifar
Introduction: Survivors of a first primary cancer (FPC) have a higher risk of developing a second primary cancer (SPC) compared to the general population, potentially driven by shared etiologic factors, genetic susceptibility, treatment-related effects, or heightened surveillance and screening. However, this elevated risk has not been well-characterized in the context of the rising incidence rate of adult early-onset cancers. Methods: Using data from 9 cancer registries in the U.S. from 1975 to 2022 in the Surveillance, Epidemiology, and End Results (SEER) Program, we estimated 5-year cumulative incidence of invasive SPC among those diagnosed with invasive FPC and the average annual percent change (AAPC) by age at FPC diagnosis (18-29, 30-49, 50-59, 60-69, 70-79, 80+), and examined these trends by sex and race/ethnicity. Results: Among FPC survivors, the age-standardized 5-year cumulative incidence of SPC steadily increased from 4.10 [3.90, 4.29]% to 6.54 [6.38, 6.69]% with AAPC of 1.12 [1.03, 1.20]% during the study period. The cumulative incidence increased across all age groups at FPC diagnosis. Among early-onset cancer survivors (i.e., those with FPC diagnosis at age 18-49 years old), female individuals had a higher SPC cumulative incidence than male individuals over the study period. However, the increase over time was steeper among males (e.g., for age 30-49 years old, AAPC: 1.59 [1.20, 1.98]% vs. 0.57 [0.37, 0.78]%), making the cumulative incidences similar in males and females by the end of the study period. Among those with FPC diagnosis at age 30-49 years old, the SPC cumulative incidence increased for all racial/ethnic groups, but the increase was steeper for Hispanic and non-Hispanic (NH) Asian or Pacific Islander (API) individuals compared to NH Black and NH White individuals. Notably, NH API individuals had a higher AAPC at this age group than at older age groups, a pattern unique to this racial/ethnic group. Among those with FPC diagnosis at age 18-29 years old, the trends were inconsistent across racial and ethnic groups, with positive AAPC for NH White individuals (1.93 [1.35, 2.51]%) and negative AAPC for Hispanic individuals (-2.59 [-4.26, -0.89]%). Conclusion: For nearly five decades, the burden of SPC following early-onset cancer has risen steadily across demographic groups. These trends suggest a compounded burden of cancer for more recent generations, who face an elevated risk of both an early-onset first cancer and a subsequent cancer, which may also occur at a young age. Potential drivers of these patterns, including improved survival, harmful treatment effects, and other etiologic factors, should be investigated in future research. Citation Format: Sunyeop Lee, Erica J. Lee Argov, Parisa Tehranifar. Trends in the Cumulative Incidence of Second Primary Cancers Among Survivors of Early-Onset Cancer in the United States, 1975-2022 [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Ear
与一般人群相比，第一原发性癌症（FPC）的幸存者发生第二原发性癌症（SPC）的风险更高，这可能是由共同的病因、遗传易感性、治疗相关效应或加强监测和筛查所驱动的。然而，在成人早发性癌症发病率上升的背景下，这种升高的风险并没有得到很好的表征。方法：利用美国监测、流行病学和最终结果（SEER）项目中从1975年到2022年9个癌症登记处的数据，我们估计了浸润性FPC患者的5年累积浸润性SPC发病率，以及FPC诊断时年龄（18-29岁、30-49岁、50-59岁、60-69岁、70-79岁、80岁以上）的平均年百分比变化（AAPC），并按性别和种族/民族检查了这些趋势。结果：在FPC幸存者中，研究期间年龄标准化5年累计SPC发病率从4.10[3.90,4.29]%稳步上升至6.54 [6.38,6.69]%，AAPC为1.12[1.03,1.20]%。在FPC诊断时，所有年龄组的累积发病率均有所增加。在早发性癌症幸存者（即18-49岁诊断为FPC的患者）中，女性个体在研究期间的SPC累积发病率高于男性个体。然而，随着时间的推移，男性的增加幅度更大（例如，在30-49岁年龄段，AAPC: 1.59 [1.20, 1.98]% vs. 0.57[0.37, 0.78]%），使得男性和女性的累积发病率在研究期结束时相似。在30-49岁诊断为FPC的人群中，所有种族/族裔群体的SPC累积发病率都有所增加，但与NH黑人和NH白人相比，西班牙裔和非西班牙裔（NH）亚洲人或太平洋岛民（API）个体的增加幅度更大。值得注意的是，NH API个体在该年龄组的AAPC高于较年长年龄组，这是该种族/族裔群体特有的模式。在18-29岁诊断为FPC的人群中，不同种族和民族的趋势不一致，NH白人的AAPC阳性（1.93[1.35,2.51]%），西班牙裔的AAPC阴性（-2.59[-4.26,-0.89]%）。结论：近50年来，早发性癌症后的SPC负担在不同人群中稳步上升。这些趋势表明，对最近几代人来说，癌症的负担是复杂的，他们面临着患早发性第一种癌症和随后癌症的风险增加，这也可能发生在年轻时。这些模式的潜在驱动因素，包括生存率的提高、有害的治疗效果和其他病因因素，应该在未来的研究中进行调查。引用格式：Sunyeop Lee， Erica J. Lee Argov, Parisa Tehranifar。1975-2022年美国早发性癌症幸存者中第二原发癌累积发病率趋势[摘要]。摘自：美国癌症研究协会癌症研究特别会议论文集：早发性癌症的增加——知识差距和研究机会；2025年12月10-13日；加拿大蒙特利尔，QC。费城（PA）： AACR；临床癌症研究2025；31(23_supl): no B022。
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Background: Early-onset colorectal cancer (EOCRC) is rising among adults aged 18–49, with disproportionately high mortality rates observed in Southeast. Hispanic adults frequently experience lifestyle-related and cardiometabolic health challenges, such as poor diet quality, obesity, and elevated rates of diabetes and hypertension, that could contribute to increased risk of developing CRC. Most CRC risk research has focused on White/ Black populations, often excluding other racial minorities or younger adults due to underrepresentation in datasets. Thus, we evaluated various contributing factors of CRC risk among Hispanic adults aged 18-49 years, both overall and stratified by sex and age. Methods: We used the National Cancer Institute’s Colorectal Cancer Risk Assessment Tool (CCRAT), supplemented with clinical indicators (blood pressure, glucose, and cholesterol), to enhance CRC risk assessment. While CCRAT isn’t validated for adults under 50 or Hispanic populations, its core variables combined with clinical data may offer useful insights for early CRC prevention strategies. Data were collected during a health fair held in Trenton, South Carolina in July 2025, specifically organized to serve Hispanic farm workers, with interpretation services provided. Variables included demographics (sex, age), body mass index, diet and physical activity, medical history (aspirin use, CRC screening, polyps), family history of CRC, and clinical indicators. Descriptive statistics were used. Results: Of the 34 young Hispanic adults, most were female (61.8%), overweight/obese (76.5%), physically active (70.6%), and regularly consumed vegetables (88.2%). Few used aspirin frequently, and none reported polyps or a family history of CRC. There were around 47.1% of participants who had elevated blood pressure (BP; Systolic BP ≥ 120 and/or Diastolic BP ≥ 80), 8.8% of those who had high glucose levels (≥126 mg/dL), and 11.8% of those who had high total cholesterol levels (≥200 mg/dL). All adults with elevated glucose levels were either females or aged 31-49, and among those with high cholesterol, 75% were female. Additionally, 65.4% of females aged 31-49 were classified as overweight or obese. Notably, two 47-year-old females, eligible for CRC screening under the updated age threshold of 45, had not been screened; however, both presenting with elevated BP. Descriptively, no clear patterns emerged by sex or age in relation to other factors. Conclusions: While this community-based pilot study uncovered unexpected patterns among racial minorities using self-reported CCRAT data, clinical findings indicated minor cardiometabolic risks in young Hispanic women. The observed discrepancies between data sources may be influenced by social desirability bias. Despite limitations, the identified factors could be linked to increased CRC susceptibility and warrant further investigation in these populations. This preliminary data may also support local efforts to promote healthy behaviors
背景：早发性结直肠癌（EOCRC）在18-49岁的成年人中呈上升趋势，东南地区的死亡率高得不成比例。西班牙裔成年人经常经历与生活方式相关的心脏代谢健康挑战，如饮食质量差、肥胖、糖尿病和高血压发病率升高，这些都可能导致患结直肠癌的风险增加。大多数CRC风险研究集中在白人/黑人人群，由于数据集中代表性不足，通常排除其他少数种族或年轻人。因此，我们评估了18-49岁西班牙裔成年人结直肠癌风险的各种影响因素，包括总体因素和按性别和年龄分层的因素。方法：采用美国国家癌症研究所大肠癌风险评估工具（CCRAT），辅以临床指标（血压、血糖、胆固醇），加强结直肠癌风险评估。虽然CCRAT尚未在50岁以下的成年人或西班牙裔人群中得到验证，但其核心变量与临床数据相结合可能为早期CRC预防策略提供有用的见解。数据是在2025年7月在南卡罗来纳州特伦顿举行的卫生博览会期间收集的，该博览会专门为西班牙裔农场工人组织，并提供口译服务。变量包括人口统计学（性别、年龄）、体重指数、饮食和体力活动、病史（阿司匹林使用、结直肠癌筛查、息肉）、结直肠癌家族史和临床指标。采用描述性统计。结果：在34名年轻的西班牙裔成年人中，大多数是女性（61.8%），超重/肥胖（76.5%），身体活跃（70.6%），经常食用蔬菜（88.2%）。很少有人经常使用阿司匹林，没有人报告有息肉或CRC家族史。大约47.1%的参与者血压升高（BP；收缩压≥120和/或舒张压≥80），8.8%的参与者血糖水平高（≥126 mg/dL）， 11.8%的参与者总胆固醇水平高（≥200 mg/dL）。所有血糖水平升高的成年人要么是女性，要么是31-49岁的人，而在高胆固醇人群中，75%是女性。此外，年龄在31-49岁的女性中有65.4%被归类为超重或肥胖。值得注意的是，有两名47岁的女性，在更新的年龄阈值45岁以下有资格进行CRC筛查，但没有接受筛查；但两者均表现为血压升高。描述性地说，与其他因素相关的性别或年龄没有出现明确的模式。结论：虽然这项以社区为基础的试点研究使用自我报告的CCRAT数据揭示了少数种族中意想不到的模式，但临床结果表明年轻西班牙裔女性有轻微的心脏代谢风险。观察到的数据源之间的差异可能受到社会期望偏差的影响。尽管存在局限性，但已确定的因素可能与CRC易感性增加有关，值得在这些人群中进一步调查。这些初步数据也可能支持当地努力促进健康行为，监测心脏代谢健康，并提高年轻西班牙裔妇女的CRC筛查意识。引用格式：蔡梦涵，张冬雨，Bayu B. Bekele，黄颖，Pamela Cromer, Debbie Layman，朱海东，董彦斌。以社区为基础的西班牙裔年轻人结直肠癌易感性和心脏代谢风险的试点研究[摘要]。摘自：美国癌症研究协会癌症研究特别会议论文集：早发性癌症的增加——知识差距和研究机会；2025年12月10-13日；加拿大蒙特利尔，QC。费城（PA）： AACR；临床癌症研究2025；31(23_supl): no A033。
{"title":"Abstract A033: Community-Based Pilot Study of Colorectal Cancer Susceptibility and Cardiometabolic Risk in Young Hispanic Adults","authors":"Meng-Han Tsai, Dongyu Zhang, Bayu B. Bekele, Ying Huang, Pamela Cromer, Debbie Layman, Haidong Zhu, Yanbin Dong","doi":"10.1158/1557-3265.earlyonsetca25-a033","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-a033","url":null,"abstract":"Background: Early-onset colorectal cancer (EOCRC) is rising among adults aged 18–49, with disproportionately high mortality rates observed in Southeast. Hispanic adults frequently experience lifestyle-related and cardiometabolic health challenges, such as poor diet quality, obesity, and elevated rates of diabetes and hypertension, that could contribute to increased risk of developing CRC. Most CRC risk research has focused on White/ Black populations, often excluding other racial minorities or younger adults due to underrepresentation in datasets. Thus, we evaluated various contributing factors of CRC risk among Hispanic adults aged 18-49 years, both overall and stratified by sex and age. Methods: We used the National Cancer Institute’s Colorectal Cancer Risk Assessment Tool (CCRAT), supplemented with clinical indicators (blood pressure, glucose, and cholesterol), to enhance CRC risk assessment. While CCRAT isn’t validated for adults under 50 or Hispanic populations, its core variables combined with clinical data may offer useful insights for early CRC prevention strategies. Data were collected during a health fair held in Trenton, South Carolina in July 2025, specifically organized to serve Hispanic farm workers, with interpretation services provided. Variables included demographics (sex, age), body mass index, diet and physical activity, medical history (aspirin use, CRC screening, polyps), family history of CRC, and clinical indicators. Descriptive statistics were used. Results: Of the 34 young Hispanic adults, most were female (61.8%), overweight/obese (76.5%), physically active (70.6%), and regularly consumed vegetables (88.2%). Few used aspirin frequently, and none reported polyps or a family history of CRC. There were around 47.1% of participants who had elevated blood pressure (BP; Systolic BP ≥ 120 and/or Diastolic BP ≥ 80), 8.8% of those who had high glucose levels (≥126 mg/dL), and 11.8% of those who had high total cholesterol levels (≥200 mg/dL). All adults with elevated glucose levels were either females or aged 31-49, and among those with high cholesterol, 75% were female. Additionally, 65.4% of females aged 31-49 were classified as overweight or obese. Notably, two 47-year-old females, eligible for CRC screening under the updated age threshold of 45, had not been screened; however, both presenting with elevated BP. Descriptively, no clear patterns emerged by sex or age in relation to other factors. Conclusions: While this community-based pilot study uncovered unexpected patterns among racial minorities using self-reported CCRAT data, clinical findings indicated minor cardiometabolic risks in young Hispanic women. The observed discrepancies between data sources may be influenced by social desirability bias. Despite limitations, the identified factors could be linked to increased CRC susceptibility and warrant further investigation in these populations. This preliminary data may also support local efforts to promote healthy behaviors","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"113 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717379","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}
Pub Date : 2025-12-10DOI: 10.1158/1557-3265.earlyonsetca25-b033
Farzana Sultana
Background: Cervical cancer is the second most prevalent cancer among females, following breast cancer, accounting for 13.3% of cases, whereas breast cancer accounts for 18% (WHO, 2022, version 11). The mortality rate of cervical cancer is around 5%, with post-menopausal patients being the most frequently affected group. Older patients tend to present at more advanced stages of the disease, leading to poorer treatment outcomes compared to those in the reproductive age group. This study aims to compare the treatment outcomes between reproductive-aged women and post-menopausal women. Methodology: Data were collected from Chittagong Health Point Hospital Ltd in Bangladesh, spanning from September 2019 to May 2023, focusing on cervical cancer treatment outcomes, including hysterectomy followed by chemotherapy and radiotherapy, with follow-ups at 3- and 6-months post-treatment. Results: A total of 35 patient records were analyzed. Of these, 15 (42.85%) were under 45 years old (reproductive age group), and 20 (57.15%) were over 50 years old (post-menopausal group). Most younger patients (73.33%) were diagnosed at an early stage (1A-1B1), while 4 out of 15 (26.66%) were diagnosed at a locally advanced stage (1B2-4A). After treatment, 93.33% of the younger patients showed positive prognoses. At the 3-month follow-up, two patients (13.33%) were found to have stage 1 cancer and underwent further chemotherapy and radiotherapy, achieving remission by the 6-month follow-up. One patient (6.67%) passed away during treatment. Among post-menopausal women, 65% (13 out of 20) were diagnosed at a locally advanced stage, with only 7 patients (53.85%) fully recovering by the 6-month follow-up. Four patients (20%) presented with advanced stage (4B) cancer and showed poor outcomes. Only three patients (15%) were diagnosed at an early stage, with relatively better prognoses. Notably, 35% (7 out of 20) refused to continue treatment, and 3 patients (15%) died during their treatment. Conclusion: The data indicate that younger patients are more likely to be diagnosed early, resulting in significantly better prognoses compared to their older counterparts. Citation Format: Farzana Sultana. A Comparative Study of Cervical Cancer Treatment Outcomes Between Reproductive-Aged and Post-Menopausal Women in a Tertiary Hospital in Bangladesh. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl): nr B033.
背景：宫颈癌是女性中发病率第二高的癌症，仅次于乳腺癌，占13.3%，而乳腺癌占18% （WHO, 2022, version 11）。宫颈癌的死亡率约为5%，绝经后患者是最常受影响的群体。老年患者往往出现在疾病的更晚期，与育龄组相比，导致治疗效果较差。本研究旨在比较育龄妇女和绝经后妇女的治疗结果。方法：数据收集自孟加拉国吉大港健康点医院有限公司，时间跨度为2019年9月至2023年5月，重点关注宫颈癌治疗结果，包括子宫切除术后化疗和放疗，并在治疗后3个月和6个月进行随访。结果：共分析35例患者病历。其中45岁以下15例（42.85%）为生育年龄组，50岁以上20例（57.15%）为绝经后组。大多数年轻患者（73.33%）诊断为早期（1A-1B1），而15名患者中有4名（26.66%）诊断为局部晚期（1B2-4A）。经治疗后，93.33%的年轻患者预后良好。随访3个月，发现2例（13.33%）患者为1期癌症，并进一步进行了化疗和放疗，6个月随访时缓解。1例患者（6.67%）在治疗过程中死亡。在绝经后妇女中，65%（13 / 20）被诊断为局部晚期，只有7例（53.85%）患者在6个月的随访中完全康复。4例（20%）患者表现为晚期（4B）癌症，预后较差。只有3名患者（15%）在早期被诊断出来，预后相对较好。值得注意的是，35%（20人中有7人）拒绝继续治疗，3名患者（15%）在治疗期间死亡。结论：数据表明，年轻患者更有可能被早期诊断，与老年患者相比，预后明显更好。引文格式：Farzana Sultana。孟加拉国某三级医院育龄妇女与绝经后妇女宫颈癌治疗效果的比较研究[摘要]。摘自：美国癌症研究协会癌症研究特别会议论文集：早发性癌症的增加——知识差距和研究机会；2025年12月10-13日；加拿大蒙特利尔，QC。费城（PA）： AACR；临床癌症研究2025；31(23_supl): no B033。
{"title":"Abstract B033: A Comparative Study of Cervical Cancer Treatment Outcomes Between Reproductive-Aged and Post-Menopausal Women in a Tertiary Hospital in Bangladesh.","authors":"Farzana Sultana","doi":"10.1158/1557-3265.earlyonsetca25-b033","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-b033","url":null,"abstract":"Background: Cervical cancer is the second most prevalent cancer among females, following breast cancer, accounting for 13.3% of cases, whereas breast cancer accounts for 18% (WHO, 2022, version 11). The mortality rate of cervical cancer is around 5%, with post-menopausal patients being the most frequently affected group. Older patients tend to present at more advanced stages of the disease, leading to poorer treatment outcomes compared to those in the reproductive age group. This study aims to compare the treatment outcomes between reproductive-aged women and post-menopausal women. Methodology: Data were collected from Chittagong Health Point Hospital Ltd in Bangladesh, spanning from September 2019 to May 2023, focusing on cervical cancer treatment outcomes, including hysterectomy followed by chemotherapy and radiotherapy, with follow-ups at 3- and 6-months post-treatment. Results: A total of 35 patient records were analyzed. Of these, 15 (42.85%) were under 45 years old (reproductive age group), and 20 (57.15%) were over 50 years old (post-menopausal group). Most younger patients (73.33%) were diagnosed at an early stage (1A-1B1), while 4 out of 15 (26.66%) were diagnosed at a locally advanced stage (1B2-4A). After treatment, 93.33% of the younger patients showed positive prognoses. At the 3-month follow-up, two patients (13.33%) were found to have stage 1 cancer and underwent further chemotherapy and radiotherapy, achieving remission by the 6-month follow-up. One patient (6.67%) passed away during treatment. Among post-menopausal women, 65% (13 out of 20) were diagnosed at a locally advanced stage, with only 7 patients (53.85%) fully recovering by the 6-month follow-up. Four patients (20%) presented with advanced stage (4B) cancer and showed poor outcomes. Only three patients (15%) were diagnosed at an early stage, with relatively better prognoses. Notably, 35% (7 out of 20) refused to continue treatment, and 3 patients (15%) died during their treatment. Conclusion: The data indicate that younger patients are more likely to be diagnosed early, resulting in significantly better prognoses compared to their older counterparts. Citation Format: Farzana Sultana. A Comparative Study of Cervical Cancer Treatment Outcomes Between Reproductive-Aged and Post-Menopausal Women in a Tertiary Hospital in Bangladesh. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl): nr B033.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"232 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717380","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}
Pub Date : 2025-12-10DOI: 10.1158/1557-3265.earlyonsetca25-a008
Manisha Salinas
Background: The incidence of cancers diagnosed before age 50 has risen steadily over the past several decades. Survivorship research has not advanced at the same pace as these trends. Existing models of care were developed primarily for older adults and emphasize medical surveillance and risk reduction. Psychosocial dimensions, including anxiety, fear of recurrence, uncertainty about long-term health, and difficulty returning to social or professional roles, remain less consistently addressed. These needs are increasingly relevant as more individuals face the long-term impact of early-onset cancers. Methods: We are developing a digital survivorship model designed to extend support beyond the clinic and focus on psychosocial recovery in the early post-treatment period. The intervention integrates evidence-based behavioral strategies with participatory input from survivors, providers, and community partners. Features under development include educational modules, guided reflection, and interactive prompts to strengthen coping, resilience, and self-management. Evaluation will examine feasibility, acceptability, and early signals of impact using surveys, usage metrics, and qualitative interviews. Preliminary Results: Stakeholder engagement to date has demonstrated strong demand for resources that are both accessible and relevant to the life stage of early-onset survivors. Survivors report that many existing programs feel generic or better suited to older adults. Key priorities identified include managing fear of recurrence, navigating uncertainty about long-term effects, and balancing recovery with the responsibilities of family, career, and caregiving. These themes are informing design decisions and shaping evaluation measures. Conclusion: The rise in early-onset cancers creates an opportunity to expand the scope of cancer control to include survivorship as a central focus. Addressing psychosocial outcomes such as coping, resilience, and quality of life is essential for long-term health. Digital health strategies provide a scalable way to meet these needs by delivering tailored support that complements advances in prevention, detection, and treatment. Integrating survivorship into the broader response to early-onset cancers ensures progress is measured not only by survival but also by the ability of survivors to live well after treatment. Citation Format: Manisha Salinas. Psychosocial Survivorship Gaps in Early-Onset Cancers: Opportunities for Digital Health Research [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl): nr A008.
背景：在过去的几十年里，50岁之前被诊断出癌症的发病率稳步上升。生存研究并没有跟上这些趋势的步伐。现有的护理模式主要是为老年人制定的，强调医疗监督和减少风险。心理社会方面，包括焦虑、害怕复发、对长期健康的不确定以及难以重返社会或职业角色，仍然没有得到一致的解决。随着越来越多的人面临早发性癌症的长期影响，这些需求越来越重要。方法：我们正在开发一种数字生存模型，旨在将支持扩展到诊所之外，并专注于治疗后早期的心理社会康复。该干预措施将基于证据的行为策略与幸存者、提供者和社区合作伙伴的参与性投入相结合。正在开发的功能包括教育模块、引导反思和互动提示，以加强应对、恢复和自我管理。评估将检查可行性、可接受性，以及使用调查、使用度量和定性访谈的早期影响信号。初步结果：迄今为止，利益攸关方的参与表明，对可获得且与早发幸存者生命阶段相关的资源有强烈需求。幸存者报告说，许多现有的项目感觉很普通，或者更适合老年人。确定的关键优先事项包括管理对复发的恐惧，应对长期影响的不确定性，以及平衡康复与家庭、事业和照顾的责任。这些主题为设计决策提供了信息，并形成了评估措施。结论：早发性癌症的增加为扩大癌症控制的范围创造了机会，将生存作为中心焦点。处理心理社会结果，如应对、复原力和生活质量，对长期健康至关重要。数字卫生战略提供了一种可扩展的方式，通过提供量身定制的支持来满足这些需求，补充预防、检测和治疗方面的进展。将幸存者纳入对早发性癌症的更广泛的反应中，确保不仅通过生存，而且通过幸存者在治疗后良好生活的能力来衡量进展。引文格式：Manisha Salinas。早发性癌症的心理社会生存差距：数字健康研究的机会[摘要]。摘自：美国癌症研究协会癌症研究特别会议论文集：早发性癌症的增加——知识差距和研究机会；2025年12月10-13日；加拿大蒙特利尔，QC。费城（PA）： AACR；临床癌症研究2025；31(23_supl): no A008。
{"title":"Abstract A008: Psychosocial Survivorship Gaps in Early-Onset Cancers: Opportunities for Digital Health Research","authors":"Manisha Salinas","doi":"10.1158/1557-3265.earlyonsetca25-a008","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-a008","url":null,"abstract":"Background: The incidence of cancers diagnosed before age 50 has risen steadily over the past several decades. Survivorship research has not advanced at the same pace as these trends. Existing models of care were developed primarily for older adults and emphasize medical surveillance and risk reduction. Psychosocial dimensions, including anxiety, fear of recurrence, uncertainty about long-term health, and difficulty returning to social or professional roles, remain less consistently addressed. These needs are increasingly relevant as more individuals face the long-term impact of early-onset cancers. Methods: We are developing a digital survivorship model designed to extend support beyond the clinic and focus on psychosocial recovery in the early post-treatment period. The intervention integrates evidence-based behavioral strategies with participatory input from survivors, providers, and community partners. Features under development include educational modules, guided reflection, and interactive prompts to strengthen coping, resilience, and self-management. Evaluation will examine feasibility, acceptability, and early signals of impact using surveys, usage metrics, and qualitative interviews. Preliminary Results: Stakeholder engagement to date has demonstrated strong demand for resources that are both accessible and relevant to the life stage of early-onset survivors. Survivors report that many existing programs feel generic or better suited to older adults. Key priorities identified include managing fear of recurrence, navigating uncertainty about long-term effects, and balancing recovery with the responsibilities of family, career, and caregiving. These themes are informing design decisions and shaping evaluation measures. Conclusion: The rise in early-onset cancers creates an opportunity to expand the scope of cancer control to include survivorship as a central focus. Addressing psychosocial outcomes such as coping, resilience, and quality of life is essential for long-term health. Digital health strategies provide a scalable way to meet these needs by delivering tailored support that complements advances in prevention, detection, and treatment. Integrating survivorship into the broader response to early-onset cancers ensures progress is measured not only by survival but also by the ability of survivors to live well after treatment. Citation Format: Manisha Salinas. Psychosocial Survivorship Gaps in Early-Onset Cancers: Opportunities for Digital Health Research [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl): nr A008.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"139 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717385","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}
Pub Date : 2025-12-10DOI: 10.1158/1557-3265.earlyonsetca25-pr001
Ritika Modi, Ryan Hood, Divya Dasani, Catherine Blandon, Shria Kumar
Background: As early-onset colorectal cancer (EOCRC) incidence rises, identifying colorectal adenomas (CRAs) under age 50 remains a key prevention strategy. We previously published a model to predict CRA risk in individuals under 50, achieving an area under the curve (AUC) of 0.71 (PMID: 39280910). Here, we validate this in a separate cohort. We also explore whether accelerated aging could be associated with CRA risk, as prior studies have suggested. PhenoAge, a proposed biological aging metric derived from clinical lab values and associated with chronic disease and mortality risk, may capture physiological decline not reflected in chronological age. Methods: Retrospective cohort study of adults under age 50 who had a colonoscopy between 2014-2024 for benign indications (excluding those with high-risk indications, alarm symptoms, or inadequate bowel preparation). The primary outcome was pathologically confirmed CRA. The previous model was applied without refitting. Performance was assessed using area under the curve (AUC), Hosmer–Lemeshow goodness-of-fit test, and diagnostic metrics (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV)) at a pre-specified probability cutoff of 0.16. For the PhenoAge analysis, we included patients within the cohort who had available labs within 60 days of colonoscopy for the calculation of PhenoAge. We evaluated whether age acceleration (PhenoAge – chronological age) were different between persons with and without CRAs. Results: We identified 2874 persons who met inclusion criteria for inclusion in the validation cohort, median age 44 years, 230 were male (49.0%). Of these, 469 (16%) had at least 1 CRA. Applying the prior model, AUC was 0.67 (95% CI: 0.64–0.69). The overall sensitivity and specificity were 67.0% and 55.2%, respectively, with a PPV of 22.6% and a NPV of 89.5%. Performance differed across age groups: for participants under 45 years, sensitivity was 29.0% and specificity was 80.6%, while for the 45-49 age group, sensitivity was 85.7% and specificity was 21.6%. A total of 202 persons had labs available to calculate PhenoAge (median age 44 years, 32% male). Of these, 25 (12%) had >1 CRA. CRA group did not show statistically significant degrees of age acceleration (-0.3 years vs -2.8 years, p=0.12), but did show higher BMI (30 vs 26, p=0.01). There were no significant differences in race, ethnicity, marital status, or aspirin use between groups. Conclusion: External validation of our previously published risk prediction model demonstrates moderate discrimination, with higher sensitivity and precision for adults under age 45. Model refinement is needed to improve performance, but this shows excellent promise for a risk-stratified approach to EOCRC prevention in persons outside screening age. Given the median age of EOCRC diagnosis is 44, such strategies are essential. Biological age as measured by PhenoAge does not appear to improve model performance, but futu
{"title":"Abstract PR001: Risk prediction modeling for colorectal adenomas in persons under age 50: a risk-stratified approach to early onset colorectal cancer prevention","authors":"Ritika Modi, Ryan Hood, Divya Dasani, Catherine Blandon, Shria Kumar","doi":"10.1158/1557-3265.earlyonsetca25-pr001","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-pr001","url":null,"abstract":"Background: As early-onset colorectal cancer (EOCRC) incidence rises, identifying colorectal adenomas (CRAs) under age 50 remains a key prevention strategy. We previously published a model to predict CRA risk in individuals under 50, achieving an area under the curve (AUC) of 0.71 (PMID: 39280910). Here, we validate this in a separate cohort. We also explore whether accelerated aging could be associated with CRA risk, as prior studies have suggested. PhenoAge, a proposed biological aging metric derived from clinical lab values and associated with chronic disease and mortality risk, may capture physiological decline not reflected in chronological age. Methods: Retrospective cohort study of adults under age 50 who had a colonoscopy between 2014-2024 for benign indications (excluding those with high-risk indications, alarm symptoms, or inadequate bowel preparation). The primary outcome was pathologically confirmed CRA. The previous model was applied without refitting. Performance was assessed using area under the curve (AUC), Hosmer–Lemeshow goodness-of-fit test, and diagnostic metrics (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV)) at a pre-specified probability cutoff of 0.16. For the PhenoAge analysis, we included patients within the cohort who had available labs within 60 days of colonoscopy for the calculation of PhenoAge. We evaluated whether age acceleration (PhenoAge – chronological age) were different between persons with and without CRAs. Results: We identified 2874 persons who met inclusion criteria for inclusion in the validation cohort, median age 44 years, 230 were male (49.0%). Of these, 469 (16%) had at least 1 CRA. Applying the prior model, AUC was 0.67 (95% CI: 0.64–0.69). The overall sensitivity and specificity were 67.0% and 55.2%, respectively, with a PPV of 22.6% and a NPV of 89.5%. Performance differed across age groups: for participants under 45 years, sensitivity was 29.0% and specificity was 80.6%, while for the 45-49 age group, sensitivity was 85.7% and specificity was 21.6%. A total of 202 persons had labs available to calculate PhenoAge (median age 44 years, 32% male). Of these, 25 (12%) had >1 CRA. CRA group did not show statistically significant degrees of age acceleration (-0.3 years vs -2.8 years, p=0.12), but did show higher BMI (30 vs 26, p=0.01). There were no significant differences in race, ethnicity, marital status, or aspirin use between groups. Conclusion: External validation of our previously published risk prediction model demonstrates moderate discrimination, with higher sensitivity and precision for adults under age 45. Model refinement is needed to improve performance, but this shows excellent promise for a risk-stratified approach to EOCRC prevention in persons outside screening age. Given the median age of EOCRC diagnosis is 44, such strategies are essential. Biological age as measured by PhenoAge does not appear to improve model performance, but futu","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"28 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717421","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}
Pub Date : 2025-12-10DOI: 10.1158/1557-3265.earlyonsetca25-b026
Sif Ingibergsdóttir. Novitski, Sidsel Christy. Lindgaard, Jessica Xin. Hjaltelin, Kevin Zi Ming. Lim, Isabella Friis. Jørgensen, Troels Dreier. Christensen, Charlotte Vestrup. Rift, Claus Fristrup, Inna Markovna. Chen, Julia Sidenious. Johansen, Søren Brunak
Introduction Early-onset cancers are emerging globally, and an alarming upward trend of young adults below 50 are being diagnosed with cancers in the gastrointestinal tract, including pancreatic cancer. It has been proposed that the rising incidence of early-onset gastrointestinal cancers appears to be related to nonhereditary factors, such as lifestyle, environmental exposures, and individual host mechanisms. Nevertheless, the specific risk factors, molecular characteristics, and genomic patterns driving the development of early-onset pancreatic cancer (EOPC) remain unknown. In our study, we investigated whether there are differences between EOPC and LOPC (late-onset pancreatic cancer) in their disease and medication history. Method We extracted pancreatic cancer patients from the period 1978–2022 using the Danish Cancer Registry (DCR) and included their disease history from the Danish National Patient Registry as well as their medication use from the Danish National Prescription Registry. Single disease differences between EOPC and LOPC were identified using a logistic regression model, and pairwise directional co-occurrences were identified using a disease-disease trajectory software program. This program calculates significant disease pairs and the strength of their directionality, i.e., whether one of the diseases occurs significantly more before or after the other, among pancreatic cancer patients compared to over 8 million Danish controls. Subsequently, the pancreatic cancer disease patterns were analyzed according to the age at disease onset for all disease pairs found. We compare these patterns and investigate whether pancreatic cancer progression differs for EOPC and LOPC according to disease history. Finally, we investigate the medication history prior to pancreatic cancer diagnoses. Results From the DCR, we identified 35,263 pancreatic cancer patients, comprising 1,612 EOPC (≤50 years) and 33,651 LOPC (>50 years) cases. EOPC was significantly associated with infertility diagnoses, mental disorders, and injuries compared to LOPC, although subgroups of LOPC patients also had these conditions. LOPC was significantly more associated with heart diseases and diabetes mellitus. LOPC had unique disease pairs related to older age, which were not observed in EOPC. EOPC patients redeemed painkillers such as paracetamol, tramadol, and codeine closer to their pancreatic cancer diagnosis compared to LOPC. Conclusion There are differences in certain disease and medication patterns prior to pancreatic cancer diagnosis between EOPC and LOPC, although some of these patterns may also be attributed to age differences. Pancreatic cancer patients with mental disorders were diagnosed at a younger age, suggesting that lifestyle factors or an unknown shared exposure may play a role in this patient group. Citation Format: Sif Ingibergsdóttir. Novitski, Sidsel Christy. Lindgaard, Jessica Xin. Hjaltelin, Kevin Zi Ming. Lim, Isabella Friis. Jørgensen, Troe
早发性癌症正在全球范围内出现，50岁以下的年轻人被诊断患有胃肠道癌症，包括胰腺癌，呈惊人的上升趋势。有人提出，早发性胃肠道癌症发病率的上升似乎与非遗传因素有关，如生活方式、环境暴露和个体宿主机制。然而，驱动早发性胰腺癌（EOPC）发展的具体危险因素、分子特征和基因组模式尚不清楚。在我们的研究中，我们调查了EOPC和LOPC（晚发性胰腺癌）在疾病和用药史上是否存在差异。方法使用丹麦癌症登记处（DCR）提取1978-2022年期间的胰腺癌患者，并纳入丹麦国家患者登记处的疾病史以及丹麦国家处方登记处的药物使用情况。使用逻辑回归模型确定EOPC和LOPC之间的单一疾病差异，并使用疾病-疾病轨迹软件程序确定两两方向共发生。该程序计算重要疾病对及其方向性的强度，即，与800多万丹麦对照相比，胰腺癌患者中一种疾病是在另一种疾病之前还是之后显著发生。随后，根据发现的所有疾病对的发病年龄，对胰腺癌疾病模式进行分析。我们比较了这些模式，并根据病史调查EOPC和LOPC的胰腺癌进展是否不同。最后，我们调查胰腺癌诊断前的用药史。从DCR中，我们确定了35,263例胰腺癌患者，其中包括1,612例EOPC（≤50年）和33,651例LOPC（50年）。与LOPC相比，EOPC与不孕症诊断、精神障碍和损伤显著相关，尽管LOPC患者亚组也有这些情况。LOPC与心脏病和糖尿病的相关性更大。LOPC有独特的与年龄相关的疾病对，这在EOPC中未见。与LOPC相比，EOPC患者更接近胰腺癌诊断时使用扑热息痛、曲马多和可待因等止痛药。结论EOPC和LOPC在胰腺癌诊断前的某些疾病和用药模式存在差异，尽管其中一些模式也可能归因于年龄差异。患有精神障碍的胰腺癌患者在较年轻时被诊断出来，这表明生活方式因素或未知的共同暴露可能在这一患者群体中起作用。引用格式：Sif Ingibergsdóttir。诺维茨基，我是塞尔·克里斯蒂。林嘉德，杰西卡·辛。我是凯文·子明。林，我是伊莎贝拉·弗里斯。Jørgensen, Troels Dreier。Christensen, Charlotte Vestrup。Rift, Claus Fristrup, Inna Markovna。陈，茱莉亚·西德尼斯。约翰森，Søren Brunak。来自大规模登记和电子病历数据的早发性胰腺癌的诊断前疾病和用药史[摘要]。摘自：美国癌症研究协会癌症研究特别会议论文集：早发性癌症的增加——知识差距和研究机会；2025年12月10-13日；加拿大蒙特利尔，QC。费城（PA）： AACR；临床癌症研究2025；31(23_supl): no B026。
{"title":"Abstract B026: Pre-diagnostic disease and medication history in early-onset pancreatic cancer from large-scale registry and EHR data","authors":"Sif Ingibergsdóttir. Novitski, Sidsel Christy. Lindgaard, Jessica Xin. Hjaltelin, Kevin Zi Ming. Lim, Isabella Friis. Jørgensen, Troels Dreier. Christensen, Charlotte Vestrup. Rift, Claus Fristrup, Inna Markovna. Chen, Julia Sidenious. Johansen, Søren Brunak","doi":"10.1158/1557-3265.earlyonsetca25-b026","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-b026","url":null,"abstract":"Introduction Early-onset cancers are emerging globally, and an alarming upward trend of young adults below 50 are being diagnosed with cancers in the gastrointestinal tract, including pancreatic cancer. It has been proposed that the rising incidence of early-onset gastrointestinal cancers appears to be related to nonhereditary factors, such as lifestyle, environmental exposures, and individual host mechanisms. Nevertheless, the specific risk factors, molecular characteristics, and genomic patterns driving the development of early-onset pancreatic cancer (EOPC) remain unknown. In our study, we investigated whether there are differences between EOPC and LOPC (late-onset pancreatic cancer) in their disease and medication history. Method We extracted pancreatic cancer patients from the period 1978–2022 using the Danish Cancer Registry (DCR) and included their disease history from the Danish National Patient Registry as well as their medication use from the Danish National Prescription Registry. Single disease differences between EOPC and LOPC were identified using a logistic regression model, and pairwise directional co-occurrences were identified using a disease-disease trajectory software program. This program calculates significant disease pairs and the strength of their directionality, i.e., whether one of the diseases occurs significantly more before or after the other, among pancreatic cancer patients compared to over 8 million Danish controls. Subsequently, the pancreatic cancer disease patterns were analyzed according to the age at disease onset for all disease pairs found. We compare these patterns and investigate whether pancreatic cancer progression differs for EOPC and LOPC according to disease history. Finally, we investigate the medication history prior to pancreatic cancer diagnoses. Results From the DCR, we identified 35,263 pancreatic cancer patients, comprising 1,612 EOPC (≤50 years) and 33,651 LOPC (>50 years) cases. EOPC was significantly associated with infertility diagnoses, mental disorders, and injuries compared to LOPC, although subgroups of LOPC patients also had these conditions. LOPC was significantly more associated with heart diseases and diabetes mellitus. LOPC had unique disease pairs related to older age, which were not observed in EOPC. EOPC patients redeemed painkillers such as paracetamol, tramadol, and codeine closer to their pancreatic cancer diagnosis compared to LOPC. Conclusion There are differences in certain disease and medication patterns prior to pancreatic cancer diagnosis between EOPC and LOPC, although some of these patterns may also be attributed to age differences. Pancreatic cancer patients with mental disorders were diagnosed at a younger age, suggesting that lifestyle factors or an unknown shared exposure may play a role in this patient group. Citation Format: Sif Ingibergsdóttir. Novitski, Sidsel Christy. Lindgaard, Jessica Xin. Hjaltelin, Kevin Zi Ming. Lim, Isabella Friis. Jørgensen, Troe","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"26 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717473","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}
Pub Date : 2025-12-10DOI: 10.1158/1557-3265.earlyonsetca25-c030
Casidhe-Nicole R. Bethancourt, Yosuke Mitani, Michelle Zhang, Tianxia Li, Yoanna Pumpalova, Beatrice Dionigi, Joel Gabre
Background: Diet and obesity play a role in the intestinal microenvironment. High-fat diet and metabolic changes associated with obesity has been shown to increased cellular remodeling and local inflammation. Given the rise in early onset colorectal cancer, here we explore the effect of a high-fat environment in colonic organoids derived from young versus older individuals. We propose that organoids derived from younger individuals have more cellular plasticity, allow them to proliferate in high-fat environment at the cost of increased mutational burden and an altered intestinal microenvironment that increases the risk of tumor development and progression. Method: We generated organoids obtained from normal colon tissue from patients undergoing colorectal resection for colon cancer, one £45 years old and the other >60 years old. After sufficient growth, organoids were chemically passaged, counted and seeded at 50,000 cells per 50µl of Matrigel in a 24-well plate. After 2 days of growth in standard organoid media, organoids were treated with 30µM of palmitic acid. Equivalent amounts of ethanol in 1% BSA served as a control. PDOs were examined under Celigo Image Cytometer (Nexcelom) at desired time points to quantify number of organoids per well. Following treatment, RNA was obtained using RNAqueous-Micro Kit and then converted to cDNA using Bio-Rad kit. qRT-PCR Bio-Rad was conducted using iCycler RT–PCR detection system. Results: A high-fat environment led to significantly increased organoid formation in normal colon organoids in £45YO group but not in the >60YO group (mean number of organoids 245 versus 314 in £45YO-control and £45YO-exposed respectively; p-value<0.0001 and 167 versus 197 in >60YO-control and >60YO-exposed respectively; p-value 0.0892). After 96hr of growth, this significant difference was lost. Following passage and despite adjustment to normal organoid media, the £45YO-exposed group had significantly increased organoid formation capacity compared to control (mean number of organoids 94 versus 182 in £45YO-control and £45YO-exposed; p-value=0.006). TLR4 gene expressions levels were quantified and found to be significantly increased by exposure to PA in the <45YO group but not the >60YO group (p-value 0.0299). Conclusion: Using palmitic acid, a known component of a high-fat diet, we demonstrate that exposure leads to increased proliferation in colonic organoids derived from young individuals but not older individuals. Despite normalization of the environment, the second generation of organoids derived from those exposed demonstrated continued proliferation compared to control. TLR4 gene expression was also significantly increased in this group. This receptor likely may modulate inflammation in the tumor microenvironment. Citation Format: Casidhe-Nicole R. Bethancourt, Yosuke Mitani, Michelle Zhang, Tianxia Li, Yoanna Pumpalova, Beatrice Dionigi, Joel Gabre. Effect of palmitic acid
背景：饮食和肥胖在肠道微环境中发挥作用。高脂肪饮食和与肥胖相关的代谢变化已被证明会增加细胞重塑和局部炎症。鉴于早发性结直肠癌的增加，本研究探讨了高脂肪环境对来自年轻人和老年人的结肠类器官的影响。我们提出，来自年轻个体的类器官具有更多的细胞可塑性，允许它们在高脂肪环境中增殖，代价是增加突变负担和改变肠道微环境，从而增加肿瘤发生和进展的风险。方法：我们从直肠癌结肠切除术患者的正常结肠组织中获得类器官，一名45岁，另一名45岁；60岁。充分生长后，类器官化学传代，计数并在24孔板上以每50µl Matrigel 50,000个细胞播种。在标准类器官培养基中生长2天后，类器官用30µM棕榈酸处理。1% BSA中等量的乙醇作为对照。在所需的时间点，在Celigo图像细胞仪（Nexcelom）下检测pdo，以量化每孔的类器官数量。处理后，使用RNAqueous-Micro Kit获得RNA，然后使用Bio-Rad Kit转化为cDNA。Bio-Rad采用icycle RT-PCR检测系统。结果：高脂肪环境导致£45YO组正常结肠类器官形成显著增加，而&；gt；60YO组（类器官的平均数量分别为245个和314个；p值&；lt；0.0001和167个，p值&；gt；60YO组和&；gt；60YO组分别为197个；p值0.0892）。生长96小时后，这种显著的差异消失了。通过后，尽管调整到正常的类器官培养基，与对照组相比，暴露于£45yo组的类器官形成能力显著增加（类器官的平均数量为94个，而对照组和暴露于£45yo组的类器官平均数量为182个；p值=0.006）。对TLR4基因表达水平进行了定量分析，发现暴露于PA后，TLR4基因表达水平显著升高。45YO组，但不是&；gt；60YO组（p值0.0299）。结论：使用棕榈酸（一种已知的高脂肪饮食成分），我们证明暴露于棕榈酸会导致来自年轻人的结肠类器官增殖增加，而不是老年人。尽管环境恢复正常，但与对照组相比，暴露于环境中的第二代类器官仍表现出持续的增殖。TLR4基因表达也显著升高。这种受体可能调节肿瘤微环境中的炎症。引文格式：Casidhe-Nicole R. Bethancourt, Yosuke Mitani, Michelle Zhang, Tianxia Li, Yoanna Pumpalova, Beatrice Dionigi, Joel Gabre。棕榈酸暴露对年轻人和老年人正常结肠类器官的影响[摘要]。摘自：美国癌症研究协会癌症研究特别会议论文集：早发性癌症的增加——知识差距和研究机会；2025年12月10-13日；加拿大蒙特利尔，QC。费城（PA）： AACR；临床癌症研究2025；31(23_supl): no C030。
{"title":"Abstract C030: Effect of palmitic acid exposure in normal colon organoids derived from young versus older individuals","authors":"Casidhe-Nicole R. Bethancourt, Yosuke Mitani, Michelle Zhang, Tianxia Li, Yoanna Pumpalova, Beatrice Dionigi, Joel Gabre","doi":"10.1158/1557-3265.earlyonsetca25-c030","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-c030","url":null,"abstract":"Background: Diet and obesity play a role in the intestinal microenvironment. High-fat diet and metabolic changes associated with obesity has been shown to increased cellular remodeling and local inflammation. Given the rise in early onset colorectal cancer, here we explore the effect of a high-fat environment in colonic organoids derived from young versus older individuals. We propose that organoids derived from younger individuals have more cellular plasticity, allow them to proliferate in high-fat environment at the cost of increased mutational burden and an altered intestinal microenvironment that increases the risk of tumor development and progression. Method: We generated organoids obtained from normal colon tissue from patients undergoing colorectal resection for colon cancer, one £45 years old and the other &gt;60 years old. After sufficient growth, organoids were chemically passaged, counted and seeded at 50,000 cells per 50µl of Matrigel in a 24-well plate. After 2 days of growth in standard organoid media, organoids were treated with 30µM of palmitic acid. Equivalent amounts of ethanol in 1% BSA served as a control. PDOs were examined under Celigo Image Cytometer (Nexcelom) at desired time points to quantify number of organoids per well. Following treatment, RNA was obtained using RNAqueous-Micro Kit and then converted to cDNA using Bio-Rad kit. qRT-PCR Bio-Rad was conducted using iCycler RT–PCR detection system. Results: A high-fat environment led to significantly increased organoid formation in normal colon organoids in £45YO group but not in the &gt;60YO group (mean number of organoids 245 versus 314 in £45YO-control and £45YO-exposed respectively; p-value&lt;0.0001 and 167 versus 197 in &gt;60YO-control and &gt;60YO-exposed respectively; p-value 0.0892). After 96hr of growth, this significant difference was lost. Following passage and despite adjustment to normal organoid media, the £45YO-exposed group had significantly increased organoid formation capacity compared to control (mean number of organoids 94 versus 182 in £45YO-control and £45YO-exposed; p-value=0.006). TLR4 gene expressions levels were quantified and found to be significantly increased by exposure to PA in the &lt;45YO group but not the &gt;60YO group (p-value 0.0299). Conclusion: Using palmitic acid, a known component of a high-fat diet, we demonstrate that exposure leads to increased proliferation in colonic organoids derived from young individuals but not older individuals. Despite normalization of the environment, the second generation of organoids derived from those exposed demonstrated continued proliferation compared to control. TLR4 gene expression was also significantly increased in this group. This receptor likely may modulate inflammation in the tumor microenvironment. Citation Format: Casidhe-Nicole R. Bethancourt, Yosuke Mitani, Michelle Zhang, Tianxia Li, Yoanna Pumpalova, Beatrice Dionigi, Joel Gabre. Effect of palmitic acid ","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"139 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717344","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}
Pub Date : 2025-12-10DOI: 10.1158/1557-3265.earlyonsetca25-a014
Dr Nitin Gupta
Back ground: Tumor ASP (aspherecity) indicates a more irregular tumor shape and is a quantitative parameter indicating metabolic heterogeneity in tumor microenvironment. A higher degree of tumor ASP is associated with more aggressive behavior and confers a poorer prognosis. Aim: To evaluate role of tumor ASP on initial 18F-FDG PET/CT scans as a prognostic marker in patients with breast IDC. Materials and methods: Clinical and histopathological characterstics of 87 treatment naïve breast carcinoma patients (mean age 29.4 years; range, 28-83 years) and their 18F-FDG PET/CT scans performed between January 2017 and October 2023 were retrospectively analyzed in this study. Calculations: Primary tumor SULpeak, MTV and TLG were calculated using MetaVol (release 2022) and LIFEx software (version 7.6). For calculation of metabolic volumes, a fixed threshold of SUVmax of 2.5 was used. Tumor apshericity was calculated using the formula ASP % = 100 x (∛H-1), where H= (1S3)/(36πV2) where S and V are surface area and MTV of tumor respectively. Statistical analysis: All data analysis was carried out using Medcalc (version 23.0.9, MedCalc Software Ltd, Ostend, Belgium) and Minitab (version 22.1.1; Minitab LLC) statistical softwares. Cox univariate and multivariate regression analysis with forward selection were used to analyze relationship between independent variables and PFS. Kaplan - Meier curves were generated for PFS and difference in survival between groups was assessed using log-rank test. All P values were 2-sided and values of < 0.05 were considered statistically significant. Results: Mean follow-up time was 62 months for entire study sample. PFS rate among 87 patients was 81.6%. Whereas mean time period for regional or metastatic recurrence was 22 months. Cox univariate analysis revealed that primary tumor size (HR = 0.86; p value- 0.05), lymph node metastasis (HR = 14.6; p value = 0.224), negative hormonal receptor (ER, PR) status (HR =6.4; p = 0.038), HER2/neu negative status (HR =1.46; p = 0.947), SULpeak > 3.9 (HR =6.8; p value = 0.094) MTV > 6.8 mL (HR =5.8; p value = 0.046), TLG > 26.4g (HR =7.1; p value = 0.040) and ASP >19.8% (HR =15.6; p<0.0002) adversly influenced PFS. Cox multivariate analysis revealed lymph node metastasis (HR=19.4; P = 0.008) followed by ASP >19.8 (HR=17.3; P = 0.028.), and negative hormonal receptor status ((HR=14.2; P = 0.003) to be strong independent predictors of PFS. Conclusions: A pre-therapeutic tumor ASP of >19.4%, could identify breast IDC patients with reduced PFS. Tumor ASP fared better as an indicator of PFS compared to many clinico-pathological and other FGD PET/CT parameters and hence useful for prognostic stratification. Citation Format: Dr Nitin Gupta. Prognostic value of tumor asphericity on initial staging 18F- FDG PET/CT in patients with breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-On
{"title":"Abstract A014: Prognostic value of tumor asphericity on initial staging 18F- FDG PET/CT in patients with breast cancer","authors":"Dr Nitin Gupta","doi":"10.1158/1557-3265.earlyonsetca25-a014","DOIUrl":"https://doi.org/10.1158/1557-3265.earlyonsetca25-a014","url":null,"abstract":"Back ground: Tumor ASP (aspherecity) indicates a more irregular tumor shape and is a quantitative parameter indicating metabolic heterogeneity in tumor microenvironment. A higher degree of tumor ASP is associated with more aggressive behavior and confers a poorer prognosis. Aim: To evaluate role of tumor ASP on initial 18F-FDG PET/CT scans as a prognostic marker in patients with breast IDC. Materials and methods: Clinical and histopathological characterstics of 87 treatment naïve breast carcinoma patients (mean age 29.4 years; range, 28-83 years) and their 18F-FDG PET/CT scans performed between January 2017 and October 2023 were retrospectively analyzed in this study. Calculations: Primary tumor SULpeak, MTV and TLG were calculated using MetaVol (release 2022) and LIFEx software (version 7.6). For calculation of metabolic volumes, a fixed threshold of SUVmax of 2.5 was used. Tumor apshericity was calculated using the formula ASP % = 100 x (∛H-1), where H= (1S3)/(36πV2) where S and V are surface area and MTV of tumor respectively. Statistical analysis: All data analysis was carried out using Medcalc (version 23.0.9, MedCalc Software Ltd, Ostend, Belgium) and Minitab (version 22.1.1; Minitab LLC) statistical softwares. Cox univariate and multivariate regression analysis with forward selection were used to analyze relationship between independent variables and PFS. Kaplan - Meier curves were generated for PFS and difference in survival between groups was assessed using log-rank test. All P values were 2-sided and values of &lt; 0.05 were considered statistically significant. Results: Mean follow-up time was 62 months for entire study sample. PFS rate among 87 patients was 81.6%. Whereas mean time period for regional or metastatic recurrence was 22 months. Cox univariate analysis revealed that primary tumor size (HR = 0.86; p value- 0.05), lymph node metastasis (HR = 14.6; p value = 0.224), negative hormonal receptor (ER, PR) status (HR =6.4; p = 0.038), HER2/neu negative status (HR =1.46; p = 0.947), SULpeak &gt; 3.9 (HR =6.8; p value = 0.094) MTV &gt; 6.8 mL (HR =5.8; p value = 0.046), TLG &gt; 26.4g (HR =7.1; p value = 0.040) and ASP &gt;19.8% (HR =15.6; p&lt;0.0002) adversly influenced PFS. Cox multivariate analysis revealed lymph node metastasis (HR=19.4; P = 0.008) followed by ASP &gt;19.8 (HR=17.3; P = 0.028.), and negative hormonal receptor status ((HR=14.2; P = 0.003) to be strong independent predictors of PFS. Conclusions: A pre-therapeutic tumor ASP of &gt;19.4%, could identify breast IDC patients with reduced PFS. Tumor ASP fared better as an indicator of PFS compared to many clinico-pathological and other FGD PET/CT parameters and hence useful for prognostic stratification. Citation Format: Dr Nitin Gupta. Prognostic value of tumor asphericity on initial staging 18F- FDG PET/CT in patients with breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-On","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"20 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717476","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}
Pub Date : 2025-12-10DOI: 10.1158/1557-3265.earlyonsetca25-c031
Peter Cornelius, Benjamin A. Mayes, Andrew J. Dannenberg, Pierre J. Dufour, Sara Little, Douglas V. Guzior, John S. Petersen, James M. Shanahan, Bradley J. Carver
Obesity and diabetes are associated with worse prognosis for numerous malignancies. In independent non-clinical models, small molecule inhibitors of METAP2 inhibit tumor growth and induce weight loss but effects on obesity-accelerated tumor growth are unknown. SDX-7320 is a novel, optimized METAP2 inhibitor. Our first objective was to determine the effects of SDX-7320 on obesity and insulin resistance in DIO mice. Our second objective was to evaluate whether targeting METAP2 could attenuate obesity-accelerated tumor growth in DIO mice and to define underlying mechanisms. The final aim was to compare the anti-tumor activity of SDX-7320 vs. tirzepatide (TZP), a highly effective weight loss agent in DIO tumor-bearing mice. The anti-obesity activity of SDX-7320 was evaluated in male diet-induced obese (DIO) mice, following subcutaneous administration every four days. The insulin-sensitizing activity of SDX-7320 was assessed in male DIO mice using an insulin-tolerance test, following a single subcutaneous injection of SDX-7320. The effect of SDX-7320 on obesity-accelerated tumor growth was tested in male mice (lean and DIO) with B16F10 tumors, female ovariectomized mice (lean and DIO) with EO771 tumors, and male mice (lean and DIO) with MC38 tumors. The anti-tumor and anti-obesity efficacy of SDX-7320 and TZP were compared in DIO mice with MC38 tumors. Effects of these compounds on obesity were assessed by measuring body weight, adipose tissue mass and plasma adipokines. RNA-Seq was carried out to define the effects of SDX-7320 on MC38 tumors from lean and DIO mice. Untargeted metabolomics was used to compare the effects of SDX-7320 and TZP. SDX-7320 elicited weight loss in obese mice accompanied by increased insulin sensitivity, decreased plasma leptin, and increased plasma adiponectin. SDX-7320 significantly attenuated the growth of established tumors in all models tested, with greater inhibition in obese versus lean mice. Treatment with SDX-7320 led to significant alterations in MC38 tumor gene expression: increased interferon alpha- and gamma-response pathways and decreased cell cycle pathways. To assess the contribution of weight loss to anti-tumor activity, the effects of SDX-7320 and TZP were compared in DIO mice with MC38 tumors. Both agents inhibited obesity-accelerated tumor growth, but SDX-7320 was significantly more efficacious despite causing less weight loss. Plasma metabolomics revealed non-overlapping effects, consistent with distinct mechanisms of action for each agent. The potent anti-tumor activity of SDX-7320 in obesity-accelerated cancers is attributed to both direct and indirect effects, including cell cycle inhibition, immune stimulation, and favorable systemic metabolic changes occurring in association with weight loss. Since GLP-1 receptor expression in MC38 tumors was undetectable, our results with TZP support the concept that excess adipose tissue indirectly promotes tumor growth. The direct effects of SDX-7320 on tumors com
肥胖和糖尿病与许多恶性肿瘤的预后较差有关。在独立的非临床模型中，METAP2的小分子抑制剂抑制肿瘤生长并诱导体重减轻，但对肥胖加速肿瘤生长的影响尚不清楚。SDX-7320是一种新型、优化的METAP2抑制剂。我们的第一个目标是确定SDX-7320对DIO小鼠肥胖和胰岛素抵抗的影响。我们的第二个目标是评估靶向METAP2是否可以减轻肥胖加速的DIO小鼠肿瘤生长，并确定潜在的机制。最终目的是比较SDX-7320与替西帕肽（TZP）在DIO荷瘤小鼠中的抗肿瘤活性。SDX-7320每4天皮下给药，在雄性饮食性肥胖（DIO）小鼠中评估其抗肥胖活性。在单次皮下注射SDX-7320后，通过胰岛素耐量试验在雄性DIO小鼠中评估SDX-7320的胰岛素增敏活性。SDX-7320对B16F10肿瘤的雄性小鼠（瘦和DIO）、EO771肿瘤的雌性去卵巢小鼠（瘦和DIO）和MC38肿瘤的雄性小鼠（瘦和DIO）的肥胖加速肿瘤生长的影响进行了测试。比较SDX-7320和TZP对MC38肿瘤小鼠的抗肿瘤和抗肥胖作用。通过测量体重、脂肪组织质量和血浆脂肪因子来评估这些化合物对肥胖的影响。采用RNA-Seq方法确定SDX-7320对瘦小鼠和DIO小鼠MC38肿瘤的影响。非靶向代谢组学用于比较SDX-7320和TZP的作用。SDX-7320引起肥胖小鼠体重减轻，同时胰岛素敏感性增加，血浆瘦素降低，血浆脂联素增加。SDX-7320在所有测试的模型中显著减弱已建立的肿瘤的生长，在肥胖小鼠中比在瘦小鼠中具有更大的抑制作用。SDX-7320治疗导致MC38肿瘤基因表达的显著改变：干扰素α和γ反应途径增加，细胞周期途径减少。为了评估减肥对抗肿瘤活性的贡献，我们比较了SDX-7320和TZP在MC38肿瘤的DIO小鼠中的作用。这两种药物都抑制了肥胖加速的肿瘤生长，但SDX-7320明显更有效，尽管体重减轻较少。血浆代谢组学显示了非重叠效应，与每种药物的不同作用机制一致。SDX-7320在肥胖加速癌症中的有效抗肿瘤活性可归因于直接和间接作用，包括细胞周期抑制、免疫刺激和与体重减轻相关的有利的全身代谢变化。由于GLP-1受体在MC38肿瘤中的表达未检测到，我们的结果与TZP支持过量脂肪组织间接促进肿瘤生长的概念。SDX-7320对肿瘤的直接作用以及脂肪组织的减少导致其抗肿瘤活性优于TZP。引文格式：Peter Cornelius， Benjamin A. Mayes, Andrew J. Dannenberg, Pierre J. Dufour, Sara Little, Douglas V. Guzior, John S. Petersen, James M. Shanahan, Bradley J. Carver。Evexomostat （SDX-7320）是一种蛋氨酸氨肽酶2型（METAP2）抑制剂，可抑制肥胖加速肿瘤生长并促进肥胖患者体重减轻。摘自：美国癌症研究协会癌症研究特别会议论文集：早发性癌症的增加——知识差距和研究机会；2025年12月10-13日；加拿大蒙特利尔，QC。费城（PA）： AACR；临床癌症研究2025；31(23_supl): no C031。
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Pub Date : 2025-12-10DOI: 10.1158/1557-3265.earlyonsetca25-c028
MIR OWAIS AYAZ, MOHD JAMAL DAR JAMAL. DAR
Glycogen synthase kinase-3beta (GSK3β) is a multifunctional serine/threonine kinase seen at the convergence of several signaling cascades. GSK3β plays a central role in PI3K signaling and Wnt/beta-catenin signaling pathways, which are the key regulators of important biological functions like cell growth, survival, metabolism, epithelial–mesenchymal transition (EMT), cell proliferation and differentiation at various stages of embryonic and adult development. Accordingly, dysregulation of GSK3β has been linked to pathogenesis of cancer, diabetes, and several neurodegenerative disorders. Therefore, pharmacological interventions to inhibit GSK3β activity is an important therapeutic strategy to counter these abnormalities. Previously, we identified a highly selective, with a better pharmacokinetic profile pyrimidinylazaindole based small molecule inhibitor of GSK3β that showed potent growth inhibition in cell based and xenograft models of KRas mutant pancreatic cancers. Pertinently, this small molecule inhibitor was seen to induce apoptosis in a β-catenin and c-Myc dependent manner. Moreover, GSK3β inhibition decreased the nuclear activity of the NF-kB p65 in KRas mutated MiaPaCa-2 cells thereby impeding the cell survival and anti-apoptotic processes in these cells as well as in the xenograft model of pancreatic cancer. Since EMT driven chemoresistance remains one of the important factors involved in pancreatic cancer progression. Overcoming drug resistance in pancreatic cancer patients poses a prominent challenge, predominantly in cancers driven by K-RAS mutation. Here in this study, we have shown that small molecule inhibitor imapacts the EMT progresson in KRAS mutant pancreatic caners through mediating significant decreases in EMT markers like N Cadherins, and slug. No detectable levels of E-cadherin were seen, however, vimentin, ZEB and snail remained unchanged. While the recently FDA approved GSK3β inhibitor, elraglusib, inhibits both alpha and beta isoforms equally and shows relatively higher half maximal inhibitory concentration however, small mole identified in our study would prove a clinically-relevant choice for its higher potency, bioavailability, pharmacokinetic and drug like properties however further analysis. This study opens up new avenues for therapeutic treatment of mutant KRas-dependent human cancers through pharmacological inhibition of GSK3β. Citation Format: MIR OWAIS AYAZ, MOHD JAMAL DAR JAMAL. DAR. GSK3β: a therapeutic target in KRAS mutant pancreatic cancers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl): nr C028.
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