<p>The combination of tarlatamab plus a PD-L1 inhibitor as maintenance therapy after first-line chemoimmunotherapy demonstrated a manageable safety profile and promising activity in patients with extensive-stage small cell lung cancer (ES-SCLC). Results of the phase 1b DeLLphi-303 trial showed that first-line maintenance with tarlatamab plus either atezolizumab or durvalumab yielded progression-free survival (PFS) and overall survival (OS) beyond what had been previously reported in trials of patients treated with first-line chemoimmunotherapy and a maintenance PD-L1 inhibitor plus lurbinectedin.<span><sup>1</sup></span></p><p>DeLLphi-303 enrolled 88 patients with ES-SCLC without disease progression after platinum–etoposide chemotherapy plus a PD-L1 inhibitor. Patients received tarlatamab with atezolizumab or durvalumab as maintenance therapy until disease progression. The median follow-up from the initiation of maintenance therapy was 18.4 months.</p><p>Common grade 3/4 adverse events included hyponatremia, anemia, and neutropenia. More than half (57%) of the patients experienced a serious adverse event, the most common of which were cytokine release syndrome (24%), pyrexia (7%), immune effector cell–associated neurotoxicity syndrome (5%), and pneumonia (5%).</p><p>With tarlatamab plus atezolizumab or durvalumab, the median PFS was 5.6 months, and the median OS was 25.3 months.</p><p>According to the DeLLphi-303 researchers, who were led by Kelly G. Paulson, MD, PhD, a clinical researcher at the Providence Swedish Cancer Institute in Edmonds, Washington, this median OS was higher than the median OS reported for atezolizumab in first-line maintenance in the IMpower133 maintenance-phase analysis (12.5 months)<span><sup>2</sup></span> and what was reported for lurbinectedin plus atezolizumab in IMforte (13.2 months).<span><sup>3</sup></span></p><p>“The current first-line treatment for patients with ES-SCLC is platinum plus etoposide and an anti-PD-L1 antibody, which is continued into the maintenance phase,” explains Daniel Morgensztern, MD, a professor of medicine at Washington University School of Medicine in St. Louis, Missouri. “More recently, the addition of lurbinectedin to maintenance atezolizumab was associated with improved OS compared to atezolizumab alone in the IMforte trial.”</p><p>Although cross-trial comparisons should be done with caution, Dr Morgensztern says that “it is already known that tarlatamab is more effective than lurbinectedin, topotecan, or amrubicin in previously treated patients based on the DeLLphi-304 study,<span><sup>4</sup></span> and the results from the DeLLphi-303 are promising.”</p><p>“T-cell engagers and antibody–drug conjugates are providing unprecedented benefit in patients with SCLC,” says Dr Morgensztern. “The tendency is for both to be moved into the first-line setting, starting either during the induction phase or maintenance. Although it is very tempting to add tarlatamab to the maintenance phase, the mo
{"title":"Tarlatamab plus anti–PD-L1 as first-line maintenance for ES-SCLC demonstrates promising results","authors":"Leah Lawrence","doi":"10.1002/cncr.70179","DOIUrl":"10.1002/cncr.70179","url":null,"abstract":"<p>The combination of tarlatamab plus a PD-L1 inhibitor as maintenance therapy after first-line chemoimmunotherapy demonstrated a manageable safety profile and promising activity in patients with extensive-stage small cell lung cancer (ES-SCLC). Results of the phase 1b DeLLphi-303 trial showed that first-line maintenance with tarlatamab plus either atezolizumab or durvalumab yielded progression-free survival (PFS) and overall survival (OS) beyond what had been previously reported in trials of patients treated with first-line chemoimmunotherapy and a maintenance PD-L1 inhibitor plus lurbinectedin.<span><sup>1</sup></span></p><p>DeLLphi-303 enrolled 88 patients with ES-SCLC without disease progression after platinum–etoposide chemotherapy plus a PD-L1 inhibitor. Patients received tarlatamab with atezolizumab or durvalumab as maintenance therapy until disease progression. The median follow-up from the initiation of maintenance therapy was 18.4 months.</p><p>Common grade 3/4 adverse events included hyponatremia, anemia, and neutropenia. More than half (57%) of the patients experienced a serious adverse event, the most common of which were cytokine release syndrome (24%), pyrexia (7%), immune effector cell–associated neurotoxicity syndrome (5%), and pneumonia (5%).</p><p>With tarlatamab plus atezolizumab or durvalumab, the median PFS was 5.6 months, and the median OS was 25.3 months.</p><p>According to the DeLLphi-303 researchers, who were led by Kelly G. Paulson, MD, PhD, a clinical researcher at the Providence Swedish Cancer Institute in Edmonds, Washington, this median OS was higher than the median OS reported for atezolizumab in first-line maintenance in the IMpower133 maintenance-phase analysis (12.5 months)<span><sup>2</sup></span> and what was reported for lurbinectedin plus atezolizumab in IMforte (13.2 months).<span><sup>3</sup></span></p><p>“The current first-line treatment for patients with ES-SCLC is platinum plus etoposide and an anti-PD-L1 antibody, which is continued into the maintenance phase,” explains Daniel Morgensztern, MD, a professor of medicine at Washington University School of Medicine in St. Louis, Missouri. “More recently, the addition of lurbinectedin to maintenance atezolizumab was associated with improved OS compared to atezolizumab alone in the IMforte trial.”</p><p>Although cross-trial comparisons should be done with caution, Dr Morgensztern says that “it is already known that tarlatamab is more effective than lurbinectedin, topotecan, or amrubicin in previously treated patients based on the DeLLphi-304 study,<span><sup>4</sup></span> and the results from the DeLLphi-303 are promising.”</p><p>“T-cell engagers and antibody–drug conjugates are providing unprecedented benefit in patients with SCLC,” says Dr Morgensztern. “The tendency is for both to be moved into the first-line setting, starting either during the induction phase or maintenance. Although it is very tempting to add tarlatamab to the maintenance phase, the mo","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70179","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145891843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tuo Lan PhD, Mei Wang MS, AnnaLynn M. Williams PhD, Matthew J. Ehrhardt MD, MS, Jennifer Q. Lanctot PhD, Zhaoming Wang PhD, Shu Jiang PhD, Kevin R. Krull PhD, Gregory T. Armstrong MD, MSCE, Melissa M. Hudson MD, Graham A. Colditz MD, DrPH, Leslie L. Robison PhD, Kirsten K. Ness PhD, Yikyung Park ScD
Background
Adult survivors of childhood cancer are at higher risk of premature aging compared to their cancer-free peers due to the cancer and its treatments. However, little is known about the effect of adherence to healthy dietary patterns on aging in childhood cancer survivors.
Methods
A cross-sectional analysis was conducted of 3322 participants (mean age, 30.5 years; standard deviation [SD], 8.4) from the St. Jude Lifetime Cohort Study. Diet was measured by a food frequency questionnaire and used to assess the Healthy Eating Index (HEI)-2015 and alternate Mediterranean diet (aMED) scores. Premature aging was assessed by the deficit accumulation index and categorized into low, medium, and high risk. Multinomial logistic regressions adjusting for confounders were used to estimate odds ratios (ORs) with 95% confidence intervlas (CIs).
Results
The mean (SD) HEI-2015 score was 60.0 (10.9) of 100, and the aMED score was 4.2 (2.0) of 9. Twenty percent and 8% of survivors were in the medium and high deficit accumulation index categories, respectively. Higher adherence to HEI-2015 (ORhigh vs. low = 0.80; 95% CI, 0.69–0.93 per 10-point increment) and aMED (ORhigh vs. low = 0.91; 95% CI, 0.84–0.98 per 1-point increment) were associated with a lower risk of premature aging. The associations remained consistent among survivors who received radiation or chemotherapy.
Conclusion
Adherence to a healthy diet may contribute to reducing the premature aging risk in adult survivors of childhood cancer. Interventions that support healthy eating in this population could potentially have benefits for long-term health outcomes.
{"title":"Adherence to healthy dietary patterns and risk of premature aging in adult survivors of childhood cancer in the St. Jude Lifetime Cohort Study","authors":"Tuo Lan PhD, Mei Wang MS, AnnaLynn M. Williams PhD, Matthew J. Ehrhardt MD, MS, Jennifer Q. Lanctot PhD, Zhaoming Wang PhD, Shu Jiang PhD, Kevin R. Krull PhD, Gregory T. Armstrong MD, MSCE, Melissa M. Hudson MD, Graham A. Colditz MD, DrPH, Leslie L. Robison PhD, Kirsten K. Ness PhD, Yikyung Park ScD","doi":"10.1002/cncr.70246","DOIUrl":"10.1002/cncr.70246","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Adult survivors of childhood cancer are at higher risk of premature aging compared to their cancer-free peers due to the cancer and its treatments. However, little is known about the effect of adherence to healthy dietary patterns on aging in childhood cancer survivors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cross-sectional analysis was conducted of 3322 participants (mean age, 30.5 years; standard deviation [SD], 8.4) from the St. Jude Lifetime Cohort Study. Diet was measured by a food frequency questionnaire and used to assess the Healthy Eating Index (HEI)-2015 and alternate Mediterranean diet (aMED) scores. Premature aging was assessed by the deficit accumulation index and categorized into low, medium, and high risk. Multinomial logistic regressions adjusting for confounders were used to estimate odds ratios (ORs) with 95% confidence intervlas (CIs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mean (SD) HEI-2015 score was 60.0 (10.9) of 100, and the aMED score was 4.2 (2.0) of 9. Twenty percent and 8% of survivors were in the medium and high deficit accumulation index categories, respectively. Higher adherence to HEI-2015 (OR<sub>high vs. low</sub> = 0.80; 95% CI, 0.69–0.93 per 10-point increment) and aMED (OR<sub>high vs. low</sub> = 0.91; 95% CI, 0.84–0.98 per 1-point increment) were associated with a lower risk of premature aging. The associations remained consistent among survivors who received radiation or chemotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Adherence to a healthy diet may contribute to reducing the premature aging risk in adult survivors of childhood cancer. Interventions that support healthy eating in this population could potentially have benefits for long-term health outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Umut Yılmaz MD, Mehmet Sinan Dal MD, Turgay Ulaş MD, Elif Birtaş Ateşoğlu MD, Fatma Keklik Karadağ MD, Meral Uluköylü Mengüç MD, Esra Terzi Demirsoy MD, Kıvanç Koruk MD, Ebru Pekgüç MD, Taner Tan MD, Uğur Hatipoğlu MD, Eda Nuhoğlu Kantarcı MD, Merve Apaydın Kayer MD, Ahmet Bahadır Ak MD, Serdar Örnek MD, Ali Durdu MD, Abdulkadir Şahin MD, Emre Osmanbaşoğlu MD, Nazik Okumuş MD, Metban Mastanzade MD, Tuğba Zorlu MD, Mert Seyhan MD, Mustafa Murat Özbalak MD, Tuğrul Elverdi MD, Asu Fergün Yılmaz MD, Derya Demir MD, Deram Büyüktaş MD, Deniz Gören MD, Sinem Civriz Bozdağ MD, Tayfur Toptas MD, Işık Atagündüz MD, Meltem Akay MD, Öner Doğan MD, Muhlis Cem Ar MD, Özgür Mehtap MD, Güray Saydam MD, Fevzi Altuntaş MD, Burhan Ferhanoğlu MD
Introduction
Rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone (R-CHOP) is a standard first-line treatment in large B-cell lymphoma (LBCL). Dose intensity is frequently reduced because of toxicity or concerns of tolerability. The true impact of such treatment modifications on the response rates is difficult to assess in nonrandomized comparisons because of complex and reciprocal interactions between various determinants of both variables. To avoid these confounding biases, this study was designed to analyze subsequent outcomes after a complete response is achieved with frontline therapy, aiming to uncover an independent link between R-CHOP dose-intensity and long-term outcomes in LBCL.
Methods
Patients treated between 2012 and 2024 were included. Reduced dose-intensity was predefined as more than 20% dose reduction for any one of the drugs for two cycles or a cumulative delay of ≥21 days. The primary and secondary objectives were the duration of complete response and the cumulative incidence of relapse (CIR), respectively.
Results
The LBCL cohort consisted of 1369 consecutive cases. For this study, 953 were eligible, with 728 and 225 patients in the dose-intense and reduced-intensity groups, respectively. Duration of complete response was significantly longer for the dose-intense group with a 3-year estimate of 87.8% vs 68.8% (hazard ratio: 0.39, p < .0001). The estimated 3-year cumulative incidence of relapse was 10.3% vs 21.4% (hazard ratio: 0.51, p = .004), favoring the dose-intense group. Reduced dose intensity was an independent risk factor on multivariate analysis for both endpoints.
Conclusions
Focusing on long-term outcomes after CR, this study demonstrates an increased risk of relapse when R-CHOP intensity is reduced, providing novel evidence that complements the association between reduced treatment intensity and inferior LBCL outcomes.
利妥昔单抗-环磷酰胺-阿霉素-长春新碱-强的松龙（R-CHOP）是大b细胞淋巴瘤（LBCL）的标准一线治疗药物。由于毒性或耐受性的考虑，剂量强度经常被降低。在非随机比较中，由于这两个变量的各种决定因素之间复杂的相互作用，很难评估这种治疗修改对反应率的真正影响。为了避免这些混杂偏差，本研究旨在分析一线治疗达到完全缓解后的后续结果，旨在揭示R-CHOP剂量强度与LBCL长期结局之间的独立联系。方法：纳入2012 ~ 2024年收治的患者。降低剂量强度被定义为任何一种药物的剂量减少超过20%，持续两个周期或累积延迟≥21天。主要和次要目标分别是完全缓解持续时间和累积复发发生率（CIR）。结果：LBCL队列包括1369例连续病例。在这项研究中，953名患者符合条件，分别有728名和225名患者被分为剂量强化组和降低强度组。剂量强化组的完全缓解持续时间明显更长，3年估计为87.8% vs 68.8%（风险比：0.39,p）。结论：关注CR后的长期结果，本研究表明R-CHOP强度降低时复发风险增加，提供了新的证据，补充了降低治疗强度与较差LBCL结果之间的关联。
{"title":"Exploring an independent association between rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone dose intensity and clinical outcomes in large B-cell lymphoma: Analyses of subsequent endpoints following a complete response in a real-world cohort of 1369 patients","authors":"Umut Yılmaz MD, Mehmet Sinan Dal MD, Turgay Ulaş MD, Elif Birtaş Ateşoğlu MD, Fatma Keklik Karadağ MD, Meral Uluköylü Mengüç MD, Esra Terzi Demirsoy MD, Kıvanç Koruk MD, Ebru Pekgüç MD, Taner Tan MD, Uğur Hatipoğlu MD, Eda Nuhoğlu Kantarcı MD, Merve Apaydın Kayer MD, Ahmet Bahadır Ak MD, Serdar Örnek MD, Ali Durdu MD, Abdulkadir Şahin MD, Emre Osmanbaşoğlu MD, Nazik Okumuş MD, Metban Mastanzade MD, Tuğba Zorlu MD, Mert Seyhan MD, Mustafa Murat Özbalak MD, Tuğrul Elverdi MD, Asu Fergün Yılmaz MD, Derya Demir MD, Deram Büyüktaş MD, Deniz Gören MD, Sinem Civriz Bozdağ MD, Tayfur Toptas MD, Işık Atagündüz MD, Meltem Akay MD, Öner Doğan MD, Muhlis Cem Ar MD, Özgür Mehtap MD, Güray Saydam MD, Fevzi Altuntaş MD, Burhan Ferhanoğlu MD","doi":"10.1002/cncr.70248","DOIUrl":"10.1002/cncr.70248","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone (R-CHOP) is a standard first-line treatment in large B-cell lymphoma (LBCL). Dose intensity is frequently reduced because of toxicity or concerns of tolerability. The true impact of such treatment modifications on the response rates is difficult to assess in nonrandomized comparisons because of complex and reciprocal interactions between various determinants of both variables. To avoid these confounding biases, this study was designed to analyze subsequent outcomes after a complete response is achieved with frontline therapy, aiming to uncover an independent link between R-CHOP dose-intensity and long-term outcomes in LBCL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients treated between 2012 and 2024 were included. Reduced dose-intensity was predefined as more than 20% dose reduction for any one of the drugs for two cycles or a cumulative delay of ≥21 days. The primary and secondary objectives were the duration of complete response and the cumulative incidence of relapse (CIR), respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The LBCL cohort consisted of 1369 consecutive cases. For this study, 953 were eligible, with 728 and 225 patients in the dose-intense and reduced-intensity groups, respectively. Duration of complete response was significantly longer for the dose-intense group with a 3-year estimate of 87.8% vs 68.8% (hazard ratio: 0.39, <i>p <</i> .0001). The estimated 3-year cumulative incidence of relapse was 10.3% vs 21.4% (hazard ratio: 0.51, <i>p =</i> .004), favoring the dose-intense group. Reduced dose intensity was an independent risk factor on multivariate analysis for both endpoints.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Focusing on long-term outcomes after CR, this study demonstrates an increased risk of relapse when R-CHOP intensity is reduced, providing novel evidence that complements the association between reduced treatment intensity and inferior LBCL outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145861718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pojsakorn Danpanichkul MD, Yanfang Pang MSc, Primrose Tothanarungroj, Disatorn Dejvajara, Donghee Kim MD, PhD, Preenapun Saokhieo, Kanokphong Suparan MD, Mark D. Muthiah MBBS, Kwanjit Duangsonk PhD, Diego Olavarria Bernal MD, Rashid N. Lui MBChB, Karn Wijarnpreecha MD, MPH, Ghassan K. Abou-Alfa MD, PhD, Michael B. Wallace MD, MPH, Lewis R. Roberts MD, PhD, Amit G. Singal MD, MS, Ju Dong Yang MD, MS
Background
Gastrointestinal (GI) cancer remains a major global health challenge. This study provides updated 2022 estimates of GI cancer incidence and mortality worldwide, along with projections of incident cases and deaths through 2050 to inform cancer control strategies.
Methods
In this population-based study, data from the GLOBOCAN 2022 database were used to examine incidence and deaths associated with GI cancer. By using global demographic projections, this study estimated the projected number of incident cases and deaths until the year 2050.
Results
By 2050, the global burden of GI cancer is projected to reach 9.06 million incident cases (+85%) and 6.42 million deaths (+93%) from 2022. Increases in incidence are projected for both females (+87%) and males (+83%), as are increases in mortality for both females (+97%) and males (+91%). Whereas the Western Pacific region will have the highest absolute burden, with 3.88 million new cases and 2.79 million deaths, the greatest relative increase is expected in Africa, with incidence and deaths rising by 157% and 160%, respectively. As measured by the Human Development Index (HDI), the steepest increases are projected in low (+151% incidence; +152% deaths) and medium (+112% incidence; +114% deaths) HDI countries. Overall, all GI cancer types are projected to increase, led by pancreatic cancer in incidence (+95%) and colorectal cancer in deaths (+103%).
Conclusions
GI cancer incidence and deaths are expected to nearly double by 2050, with increases across sexes, cancer types, and regions, especially in lower HDI countries.
{"title":"Gastrointestinal cancer statistics in 2022 and projection to 2050: GLOBOCAN estimates across 185 countries","authors":"Pojsakorn Danpanichkul MD, Yanfang Pang MSc, Primrose Tothanarungroj, Disatorn Dejvajara, Donghee Kim MD, PhD, Preenapun Saokhieo, Kanokphong Suparan MD, Mark D. Muthiah MBBS, Kwanjit Duangsonk PhD, Diego Olavarria Bernal MD, Rashid N. Lui MBChB, Karn Wijarnpreecha MD, MPH, Ghassan K. Abou-Alfa MD, PhD, Michael B. Wallace MD, MPH, Lewis R. Roberts MD, PhD, Amit G. Singal MD, MS, Ju Dong Yang MD, MS","doi":"10.1002/cncr.70245","DOIUrl":"10.1002/cncr.70245","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Gastrointestinal (GI) cancer remains a major global health challenge. This study provides updated 2022 estimates of GI cancer incidence and mortality worldwide, along with projections of incident cases and deaths through 2050 to inform cancer control strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this population-based study, data from the GLOBOCAN 2022 database were used to examine incidence and deaths associated with GI cancer. By using global demographic projections, this study estimated the projected number of incident cases and deaths until the year 2050.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>By 2050, the global burden of GI cancer is projected to reach 9.06 million incident cases (+85%) and 6.42 million deaths (+93%) from 2022. Increases in incidence are projected for both females (+87%) and males (+83%), as are increases in mortality for both females (+97%) and males (+91%). Whereas the Western Pacific region will have the highest absolute burden, with 3.88 million new cases and 2.79 million deaths, the greatest relative increase is expected in Africa, with incidence and deaths rising by 157% and 160%, respectively. As measured by the Human Development Index (HDI), the steepest increases are projected in low (+151% incidence; +152% deaths) and medium (+112% incidence; +114% deaths) HDI countries. Overall, all GI cancer types are projected to increase, led by pancreatic cancer in incidence (+95%) and colorectal cancer in deaths (+103%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>GI cancer incidence and deaths are expected to nearly double by 2050, with increases across sexes, cancer types, and regions, especially in lower HDI countries.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145861782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lan Chen MD, Ge Chen MD, Fei Tian MD, Shengtao Wei MD, Zhengmin (Min) Qian PhD, Maya Tabet PhD, Chuanbo Xie PhD, Hualiang Lin PhD
Background
Evidence is limited concerning whether and to what extent fine particulate matter pollution (particulate matter with an aerodynamic diameter less than 2.5 μm [PM2.5]) is linked to the risk and the time to occurrence of site-specific cancers along with the key constituents of PM2.5 and the sensitive exposure window.
Methods
By using data from 277,446 participants in the UK Biobank, the authors estimated exposures to PM2.5 and its 15 constituents during each participant's lifetime and at different life stages using a bilinear interpolation method. The incidence and time to occurrence of 14 cancers were ascertained. Cox proportional hazard models and accelerated failure time models were applied to investigate the associations between air pollutants and incidence risk and occurrence time of 14 cancers.
Results
During a mean follow-up of 11.15 years, 25,820 patients with incident cancer were identified. Lifetime exposure to PM2.5 and to its constituents was associated with an increased incidence risk of 12 of 14 cancers, with hazard ratios and 95% confidence intervals ranging from 1.04 (95% confidence interval, 1.01–1.07) for breast cancer to 1.18 (95% confidence interval, 1.10–1.27) for esophageal cancer. The constituents chloride ion, ammonium, nitrate, and sodium demonstrated the most pronounced effects. The middle-aged and elderly life stage (individuals aged 45 years and older) comprised the sensitive exposure window. The time to occurrence of cancers was earlier by from 0.05 years (ovarian cancer) to 1.95 years (esophageal cancer) because of overexposure to PM2.5 levels greater than 5 μg/m3.
Conclusions
Lifetime exposure to PM2.5 and its constituents might increase the risk and accelerate the onset of various cancers. Combustion-sourced and agriculture-sourced components mainly account for this influence, with the middle-aged and elderly life stage (aged 45 years and older) a sensitive exposure window.
{"title":"Associations of lifetime exposure to fine particulate matter (PM2.5) and its constituents with increased risk and earlier occurrence of 14 site-specific cancers","authors":"Lan Chen MD, Ge Chen MD, Fei Tian MD, Shengtao Wei MD, Zhengmin (Min) Qian PhD, Maya Tabet PhD, Chuanbo Xie PhD, Hualiang Lin PhD","doi":"10.1002/cncr.70240","DOIUrl":"10.1002/cncr.70240","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Evidence is limited concerning whether and to what extent fine particulate matter pollution (particulate matter with an aerodynamic diameter less than 2.5 μm [PM<sub>2.5</sub>]) is linked to the risk and the time to occurrence of site-specific cancers along with the key constituents of PM<sub>2.5</sub> and the sensitive exposure window.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>By using data from 277,446 participants in the UK Biobank, the authors estimated exposures to PM<sub>2.5</sub> and its 15 constituents during each participant's lifetime and at different life stages using a bilinear interpolation method. The incidence and time to occurrence of 14 cancers were ascertained. Cox proportional hazard models and accelerated failure time models were applied to investigate the associations between air pollutants and incidence risk and occurrence time of 14 cancers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>During a mean follow-up of 11.15 years, 25,820 patients with incident cancer were identified. Lifetime exposure to PM<sub>2.5</sub> and to its constituents was associated with an increased incidence risk of 12 of 14 cancers, with hazard ratios and 95% confidence intervals ranging from 1.04 (95% confidence interval, 1.01–1.07) for breast cancer to 1.18 (95% confidence interval, 1.10–1.27) for esophageal cancer. The constituents chloride ion, ammonium, nitrate, and sodium demonstrated the most pronounced effects. The middle-aged and elderly life stage (individuals aged 45 years and older) comprised the sensitive exposure window. The time to occurrence of cancers was earlier by from 0.05 years (ovarian cancer) to 1.95 years (esophageal cancer) because of overexposure to PM<sub>2.5</sub> levels greater than 5 μg/m<sup>3</sup>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Lifetime exposure to PM<sub>2.5</sub> and its constituents might increase the risk and accelerate the onset of various cancers. Combustion-sourced and agriculture-sourced components mainly account for this influence, with the middle-aged and elderly life stage (aged 45 years and older) a sensitive exposure window.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carlo Silvani MD, Anna Tylecki MS, Alfonso Santangelo MD, Alex Stephens MS, Jack Considine MD, Redi Gishto BS, Myles Perry BS, Sebastiano Nazzani MD, Alberto Briganti MD, Andrea Salonia MD, Francesco Montorsi MD, Nicola Nicolai MD, Emanuele Montanari MD, Craig Rogers MD, Firas Abdollah MD
Background
Penile cancer is a rare malignancy influenced by socioeconomic factors. The Area Deprivation Index (ADI) is a validated measure of neighborhood-level socioeconomic disadvantage, and its association with penile cancer stage at presentation has not been studied. This study aimed to assess the relationship between the ADI and advanced-stage disease at diagnosis in penile cancer.
Methods
A retrospective study was conducted with the Michigan Department of Health and Human Services database of patients aged ≥18 years with penile squamous cell carcinoma from 2004 to 2019. Advanced-stage disease was defined as pathological T stage ≥2, pathological evidence of nodal metastasis, or reported presence of distal metastasis. ADI scores were compared to the national median value. Univariable and multivariable logistic regression analyses were performed to assess the association between the ADI and advanced disease after adjusting for relevant covariates.
Results
Among 353 patients (median age, 72 years; 84.4% White), the median ADI score was 69. Patients were stratified into two groups on the basis of the national median; 76% were in the high-ADI group. Black patients were more prevalent in the higher ADI group (15.3% vs. 2.4%; p = .003). Advanced-stage penile cancer was more frequent in the higher ADI group (49.3% vs. 36.5%; p = .04). In multivariable analysis, each 10-point increase in the ADI was associated with 1.16-fold increased odds of advanced-stage disease (95% CI, 1.04–1.29; p = .02).
Conclusions
Greater neighborhood-level socioeconomic deprivation is associated with advanced-stage disease at penile cancer diagnosis. These findings emphasize the role of social determinants in disease presentation, and may guide targeted interventions in disadvantaged populations.
背景：阴茎癌是一种受社会经济因素影响的罕见恶性肿瘤。区域剥夺指数（ADI）是衡量社区社会经济劣势的有效指标，但其与阴茎癌发病阶段的关系尚未得到研究。本研究旨在评估阴茎癌诊断时ADI与晚期疾病之间的关系。方法：对2004 - 2019年密歇根州卫生与公众服务部数据库中年龄≥18岁的阴茎鳞状细胞癌患者进行回顾性研究。晚期疾病定义为病理T期≥2，病理证据表明淋巴结转移，或报告存在远端转移。ADI得分与全国中位数进行比较。在调整相关协变量后，进行单变量和多变量logistic回归分析以评估ADI与晚期疾病之间的关联。结果：353例患者（中位年龄72岁，白人84.4%）中位ADI评分为69。根据全国中位数将患者分为两组；76%为高adi组。黑色患者在高ADI组中更为普遍（15.3% vs. 2.4%; p = 0.003）。晚期阴茎癌在高ADI组更常见（49.3%比36.5%;p = 0.04）。在多变量分析中，ADI每增加10个点，晚期疾病的几率增加1.16倍（95% CI, 1.04-1.29; p = 0.02）。结论：较大的社区社会经济剥夺与晚期阴茎癌诊断相关。这些发现强调了社会决定因素在疾病表现中的作用，并可能指导对弱势群体进行有针对性的干预。
{"title":"Impact of the Area Deprivation Index on stage at diagnosis in penile squamous cell carcinoma: A statewide cohort analysis","authors":"Carlo Silvani MD, Anna Tylecki MS, Alfonso Santangelo MD, Alex Stephens MS, Jack Considine MD, Redi Gishto BS, Myles Perry BS, Sebastiano Nazzani MD, Alberto Briganti MD, Andrea Salonia MD, Francesco Montorsi MD, Nicola Nicolai MD, Emanuele Montanari MD, Craig Rogers MD, Firas Abdollah MD","doi":"10.1002/cncr.70241","DOIUrl":"10.1002/cncr.70241","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Penile cancer is a rare malignancy influenced by socioeconomic factors. The Area Deprivation Index (ADI) is a validated measure of neighborhood-level socioeconomic disadvantage, and its association with penile cancer stage at presentation has not been studied. This study aimed to assess the relationship between the ADI and advanced-stage disease at diagnosis in penile cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective study was conducted with the Michigan Department of Health and Human Services database of patients aged ≥18 years with penile squamous cell carcinoma from 2004 to 2019. Advanced-stage disease was defined as pathological T stage ≥2, pathological evidence of nodal metastasis, or reported presence of distal metastasis. ADI scores were compared to the national median value. Univariable and multivariable logistic regression analyses were performed to assess the association between the ADI and advanced disease after adjusting for relevant covariates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 353 patients (median age, 72 years; 84.4% White), the median ADI score was 69. Patients were stratified into two groups on the basis of the national median; 76% were in the high-ADI group. Black patients were more prevalent in the higher ADI group (15.3% vs. 2.4%; <i>p</i> = .003). Advanced-stage penile cancer was more frequent in the higher ADI group (49.3% vs. 36.5%; <i>p</i> = .04). In multivariable analysis, each 10-point increase in the ADI was associated with 1.16-fold increased odds of advanced-stage disease (95% CI, 1.04–1.29; <i>p</i> = .02).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Greater neighborhood-level socioeconomic deprivation is associated with advanced-stage disease at penile cancer diagnosis. These findings emphasize the role of social determinants in disease presentation, and may guide targeted interventions in disadvantaged populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hea Lim Choi MD, Bongseong Kim PhD, Yong-Moon Mark Park MD, PhD, Jung Eun Yoo MD, PhD, Seonghye Kim MD, PhD, Su Min Jeong MD, Kyungdo Han PhD, Dong Wook Shin MD, PhD, MBA
Background
Breast cancer risk varies across metabolic obesity phenotypes, but its associations with premenopausal status and carcinoma in situ remain unclear. The objective of this study was to investigate breast cancer risk across metabolic obesity phenotypes before and after menopause.
Methods
For this retrospective cohort study, the authors used data from the Korean National Health Insurance Service, including 2,156,798 women who underwent health screening in 2009 (883,250 premenopausal and 1,273,548 postmenopausal). Metabolic obesity phenotypes were classified by the presence or absence of obesity and metabolic syndrome: metabolically healthy obesity, metabolically unhealthy normal weight, and metabolically unhealthy obesity, with metabolically healthy normal weight as the reference category. Breast cancer risk was estimated by using multivariable-adjusted Cox proportional hazards models.
Results
Over a mean follow-up period of 11.94 years, 17,052 premenopausal and 18,870 postmenopausal women developed breast cancer. Before menopause, no significant associations were identified except for a reduced risk of carcinoma in situ among women with metabolically healthy obesity (adjusted hazard ratio, 0.80; 95% confidence interval [CI], 0.74–0.87) and metabolically unhealthy obesity (adjusted hazard ratio, 0.84; 95% CI, 0.74–0.95). After menopause, metabolically healthy obesity, metabolically unhealthy normal weight, and metabolically unhealthy obesity were associated with increased breast cancer risk (adjusted hazard ratio: 1.20 [95% CI, 1.15–1.25], 1.11 [95% CI, 1.06–1.15], and 1.40 [95% CI, 1.35–1.45], respectively).
Conclusions
After menopause, obesity was associated with elevated breast cancer risk, which was further increased by metabolic syndrome. In contrast, no elevated risk was observed before menopause. The current findings highlight differences in breast cancer risk by menopausal status across metabolic obesity phenotypes, emphasizing the need for targeted prevention strategies and further research into underlying mechanisms.
{"title":"Metabolic obesity phenotypes and breast cancer risk before and after menopause: A nationwide cohort study in South Korea","authors":"Hea Lim Choi MD, Bongseong Kim PhD, Yong-Moon Mark Park MD, PhD, Jung Eun Yoo MD, PhD, Seonghye Kim MD, PhD, Su Min Jeong MD, Kyungdo Han PhD, Dong Wook Shin MD, PhD, MBA","doi":"10.1002/cncr.70244","DOIUrl":"10.1002/cncr.70244","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Breast cancer risk varies across metabolic obesity phenotypes, but its associations with premenopausal status and carcinoma in situ remain unclear. The objective of this study was to investigate breast cancer risk across metabolic obesity phenotypes before and after menopause.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>For this retrospective cohort study, the authors used data from the Korean National Health Insurance Service, including 2,156,798 women who underwent health screening in 2009 (883,250 premenopausal and 1,273,548 postmenopausal). Metabolic obesity phenotypes were classified by the presence or absence of obesity and metabolic syndrome: metabolically healthy obesity, metabolically unhealthy normal weight, and metabolically unhealthy obesity, with metabolically healthy normal weight as the reference category. Breast cancer risk was estimated by using multivariable-adjusted Cox proportional hazards models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Over a mean follow-up period of 11.94 years, 17,052 premenopausal and 18,870 postmenopausal women developed breast cancer. Before menopause, no significant associations were identified except for a reduced risk of carcinoma in situ among women with metabolically healthy obesity (adjusted hazard ratio, 0.80; 95% confidence interval [CI], 0.74–0.87) and metabolically unhealthy obesity (adjusted hazard ratio, 0.84; 95% CI, 0.74–0.95). After menopause, metabolically healthy obesity, metabolically unhealthy normal weight, and metabolically unhealthy obesity were associated with increased breast cancer risk (adjusted hazard ratio: 1.20 [95% CI, 1.15–1.25], 1.11 [95% CI, 1.06–1.15], and 1.40 [95% CI, 1.35–1.45], respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>After menopause, obesity was associated with elevated breast cancer risk, which was further increased by metabolic syndrome. In contrast, no elevated risk was observed before menopause. The current findings highlight differences in breast cancer risk by menopausal status across metabolic obesity phenotypes, emphasizing the need for targeted prevention strategies and further research into underlying mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Harshitha Dudipala MD, Shayan S. Nazari PhD, Isabela Werneck da Cunha MD, PhD, Nathan Coligado BS, Yasmine Baca MS, Shuanzeng Wei MD, PhD, Andrew Elliott PhD, Norm D. Smith MD, Daniel M. Geynisman MD, Jacqueline T. Brown MD, Kevin K. Zarrabi MD, Neeraj Agarwal MD, Emmanuel S. Antonarakis MD, Daniel Herchenhorn MD, PhD, Rana R. McKay MD
Background
Intraductal carcinoma of the prostate (IDC-P) is an intra-acinar and/or intraductal neoplastic epithelial proliferation that is a distinct histological entity according to the 2016 World Health Organization (WHO) classification system. Clinically, it is associated with higher grade tumors and a more aggressive disease course. However, the molecular underpinnings of IDC-P are not well elucidated.
Methods
This study identified radical prostatectomy (RP) cases from the Caris Life Sciences database, classified as prostatic adenocarcinoma with grade group 4/5 or with the words “cribriform,” “necrosis,” or “intraductal” in the pathology report. Digitized hematoxylin–eosin slides underwent central pathology review by a board-certified genitourinary pathologist to identify the presence of IDC-P according to the 2022 WHO classification. IDC-P cases (n = 175) were compared to non–IDC-P cases (n = 5334). Prostatic tumor specimens were sequenced via next-generation DNA/RNA sequencing.
Results
Compared to non–IDC-P cases, the IDC-P cohort had significantly more mutations in MUTYH (4.5% vs. 1.4%; p < .01), FANCA (2.7% vs. 0.5%; p < .01), NBN (2.5% vs. 0.6%; p < .05), and MTOR (0.6% vs. 0.1%; p < .05). IDC-P tumors were enriched for DLL3 and CEACAM5 expression, with lower expression of STEAP1, TROP2, ERBB2, PSCA, and B7-H3, compared to non–IDC-P tumors. IDC-P had significantly higher neuroendocrine prostate cancer signature scores and IFN-γ signature scores, and similar androgen receptor signature scores, compared to non–IDC-P. The tumor microenvironment of IDC-P had significantly higher cell fractions of M2 macrophages and fewer dendritic cells.
Conclusions
IDC-P possesses a distinct molecular and immunological profile. Understanding these molecular underpinnings is crucial for the development of personalized treatment strategies for histologically distinct prostate cancer subsets.
背景：前列腺导管内癌（IDC-P）是一种腺泡内和/或导管内肿瘤上皮增生，根据2016年世界卫生组织（WHO）分类系统，它是一种独特的组织学实体。在临床上，它与更高级别的肿瘤和更具侵袭性的病程相关。然而，IDC-P的分子基础尚未得到很好的阐明。方法：本研究从Caris生命科学数据库中确定根治性前列腺切除术（RP）病例，这些病例被分类为4/5级前列腺腺癌，或在病理报告中伴有“筛状”、“坏死”或“导管内”字样。数字化苏木精-伊红载玻片由委员会认证的泌尿生殖病理学家进行中心病理学检查，以根据2022年世卫组织分类确定IDC-P的存在。将175例IDC-P病例与5334例非IDC-P病例进行比较。通过下一代DNA/RNA测序对前列腺肿瘤标本进行测序。结果：与非IDC-P病例相比，IDC-P队列的MUTYH突变明显更多（4.5% vs. 1.4%）。结论：IDC-P具有独特的分子和免疫学特征。了解这些分子基础对于开发针对组织学上不同的前列腺癌亚群的个性化治疗策略至关重要。
{"title":"Molecular alteration profiles characterize intraductal carcinoma of the prostate","authors":"Harshitha Dudipala MD, Shayan S. Nazari PhD, Isabela Werneck da Cunha MD, PhD, Nathan Coligado BS, Yasmine Baca MS, Shuanzeng Wei MD, PhD, Andrew Elliott PhD, Norm D. Smith MD, Daniel M. Geynisman MD, Jacqueline T. Brown MD, Kevin K. Zarrabi MD, Neeraj Agarwal MD, Emmanuel S. Antonarakis MD, Daniel Herchenhorn MD, PhD, Rana R. McKay MD","doi":"10.1002/cncr.70238","DOIUrl":"10.1002/cncr.70238","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intraductal carcinoma of the prostate (IDC-P) is an intra-acinar and/or intraductal neoplastic epithelial proliferation that is a distinct histological entity according to the 2016 World Health Organization (WHO) classification system. Clinically, it is associated with higher grade tumors and a more aggressive disease course. However, the molecular underpinnings of IDC-P are not well elucidated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study identified radical prostatectomy (RP) cases from the Caris Life Sciences database, classified as prostatic adenocarcinoma with grade group 4/5 or with the words “cribriform,” “necrosis,” or “intraductal” in the pathology report. Digitized hematoxylin–eosin slides underwent central pathology review by a board-certified genitourinary pathologist to identify the presence of IDC-P according to the 2022 WHO classification. IDC-P cases (<i>n</i> = 175) were compared to non–IDC-P cases (<i>n</i> = 5334). Prostatic tumor specimens were sequenced via next-generation DNA/RNA sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to non–IDC-P cases, the IDC-P cohort had significantly more mutations in MUTYH (4.5% vs. 1.4%; <i>p</i> < .01), FANCA (2.7% vs. 0.5%; <i>p</i> < .01), NBN (2.5% vs. 0.6%; <i>p</i> < .05), and MTOR (0.6% vs. 0.1%; <i>p</i> < .05). IDC-P tumors were enriched for DLL3 and CEACAM5 expression, with lower expression of STEAP1, TROP2, ERBB2, PSCA, and B7-H3, compared to non–IDC-P tumors. IDC-P had significantly higher neuroendocrine prostate cancer signature scores and IFN-γ signature scores, and similar androgen receptor signature scores, compared to non–IDC-P. The tumor microenvironment of IDC-P had significantly higher cell fractions of M2 macrophages and fewer dendritic cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>IDC-P possesses a distinct molecular and immunological profile. Understanding these molecular underpinnings is crucial for the development of personalized treatment strategies for histologically distinct prostate cancer subsets.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Noemi A. Fuentes Bolanos MD, PhD, Philip J. Lupo PhD, MPH, Katherine M. Tucker MD, PhD, Douglas S. Hawkins MD, Christopher C. Porter MD, Anita Villani MD, MSc,, Logan G. Spector PhD
Background
Taking a family history of cancer (FH) is essential for identifying individuals with heritable cancer predisposition. Project:EveryChild (Children's Oncology Group [COG] trial APEC14B1), the registration and biobanking protocol of the COG, includes suggested questions about FH in first-degree relatives and personal history of genetic syndromes (GS) in pediatric oncology patients. The validity of these items is unclear; therefore, the authors assessed the data quality and face validity of the responses.
Methods
The authors analyzed case report forms regarding FH and GS of 30,157 participants (aged birth to 21 years) with newly diagnosed pediatric cancer enrolled in APEC14B1. FH and GS data were manually curated to interpret the responses and group them into categories, followed by face validity assessment—defined as the extent to which the information provided represented what it was intended to capture.
Results
Responses were provided for 65.7% of participants (n = 19,810), with 6.1% reporting FH (n = 1204). Of those, 97.9% (n = 1178) included sufficient free-text detail to assess face validity, although 49.4% required manual interpretation. Among FH reports, 48.3% (n = 595) were suggestive of heritable cancer risk. GS was reported in 4.3% of responders (n = 863), with 93.3% (n = 780) showing face validity after curation. Down syndrome (n = 302) and neurofibromatosis type 1 (n = 93) were the most frequently reported syndromes, with neurofibromatosis type 1 most common in patients who had central nervous system tumors.
Conclusions
Despite limitations and the need for manual curation, FH and GS data collected by using proposed questions were sufficient to identify known heritable cancer patterns. These findings support questionnaire-based data collection and highlight areas for improvement.
{"title":"Frequency and face validity of reported family history of cancer in first-degree relatives and genetic syndromes among children with cancer in Project:EveryChild: A report from the Children’s Oncology Group","authors":"Noemi A. Fuentes Bolanos MD, PhD, Philip J. Lupo PhD, MPH, Katherine M. Tucker MD, PhD, Douglas S. Hawkins MD, Christopher C. Porter MD, Anita Villani MD, MSc,, Logan G. Spector PhD","doi":"10.1002/cncr.70231","DOIUrl":"10.1002/cncr.70231","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Taking a family history of cancer (FH) is essential for identifying individuals with heritable cancer predisposition. Project:EveryChild (Children's Oncology Group [COG] trial APEC14B1), the registration and biobanking protocol of the COG, includes suggested questions about FH in first-degree relatives and personal history of genetic syndromes (GS) in pediatric oncology patients. The validity of these items is unclear; therefore, the authors assessed the data quality and face validity of the responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The authors analyzed case report forms regarding FH and GS of 30,157 participants (aged birth to 21 years) with newly diagnosed pediatric cancer enrolled in APEC14B1. FH and GS data were manually curated to interpret the responses and group them into categories, followed by face validity assessment—defined as the extent to which the information provided represented what it was intended to capture.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Responses were provided for 65.7% of participants (<i>n</i> = 19,810), with 6.1% reporting FH (<i>n</i> = 1204). Of those, 97.9% (<i>n</i> = 1178) included sufficient free-text detail to assess face validity, although 49.4% required manual interpretation. Among FH reports, 48.3% (<i>n</i> = 595) were suggestive of heritable cancer risk. GS was reported in 4.3% of responders (<i>n</i> = 863), with 93.3% (<i>n</i> = 780) showing face validity after curation. Down syndrome (<i>n</i> = 302) and neurofibromatosis type 1 (<i>n</i> = 93) were the most frequently reported syndromes, with neurofibromatosis type 1 most common in patients who had central nervous system tumors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Despite limitations and the need for manual curation, FH and GS data collected by using proposed questions were sufficient to identify known heritable cancer patterns. These findings support questionnaire-based data collection and highlight areas for improvement.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jaclyn LoPiccolo MD, PhD, Angela C. Tramontano MPH, Narjust Florez MD, Bruce E. Johnson MD, Alexander Gusev PhD, David C. Christiani MD, MPH, Pasi A. Jänne MD, PhD
Background
Although the incidence of several cancers diagnosed before age 50 years has increased, contemporary trends in early-onset lung cancer remain poorly defined, particularly across histologic and sociodemographic subgroups.
Methods
A population-based cohort study was conducted via Surveillance, Epidemiology, and End Results 22 Program registries of 81,568 individuals diagnosed with lung cancer at age 20–49 years from 2000 to 2021. Age-adjusted incidence rates and annual percent change (APC) were estimated via National Cancer Institute Joinpoint regression. Overall trends were stratified by histology, sex, race/ethnicity, and state-level smoking prevalence.
Results
From 2000 to 2021, early-onset lung cancer incidence declined overall (average APC, −3.81%; 95% CI, −4.01% to −3.64%; p < .0001), which contrasts with rising early-onset colorectal and female breast cancers. Declines among females occurred later but were steeper for lung adenocarcinoma (LUAD; −5.14% vs. −2.82%), whereas males declined faster for non–small cell lung cancer (NSCLC) and overall. Female declines were slower relative to males in Hispanic and non-Hispanic (NH) Black individuals (2.3- and 1.08-fold difference, respectively), whereas NH White females declined 1.3-fold faster than males. Among Asian females, NSCLC incidence did not decline, and LUAD increased through 2017 (+2.45%) and remained stable in Hispanic females. In high-smoking states, male rates declined steadily (−4.32%), whereas female rates were stable until 2010, then dropped sharply, and converged with males by 2021. In low-smoking states, male rates declined 48.75% faster than female rates (−4.76% vs. −3.20%).
Conclusions
Early-onset lung cancer incidence declined overall from 2000 to 2021, except for persistent or rising LUAD among Asian and Hispanic females, which implicates emerging non-tobacco risk factors and highlights the need for targeted prevention.
{"title":"Patterns of lung cancer incidence in adults diagnosed under age 50 in the United States, 2000–2021","authors":"Jaclyn LoPiccolo MD, PhD, Angela C. Tramontano MPH, Narjust Florez MD, Bruce E. Johnson MD, Alexander Gusev PhD, David C. Christiani MD, MPH, Pasi A. Jänne MD, PhD","doi":"10.1002/cncr.70217","DOIUrl":"10.1002/cncr.70217","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although the incidence of several cancers diagnosed before age 50 years has increased, contemporary trends in early-onset lung cancer remain poorly defined, particularly across histologic and sociodemographic subgroups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A population-based cohort study was conducted via Surveillance, Epidemiology, and End Results 22 Program registries of 81,568 individuals diagnosed with lung cancer at age 20–49 years from 2000 to 2021. Age-adjusted incidence rates and annual percent change (APC) were estimated via National Cancer Institute Joinpoint regression. Overall trends were stratified by histology, sex, race/ethnicity, and state-level smoking prevalence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From 2000 to 2021, early-onset lung cancer incidence declined overall (average APC, −3.81%; 95% CI, −4.01% to −3.64%; <i>p</i> < .0001), which contrasts with rising early-onset colorectal and female breast cancers. Declines among females occurred later but were steeper for lung adenocarcinoma (LUAD; −5.14% vs. −2.82%), whereas males declined faster for non–small cell lung cancer (NSCLC) and overall. Female declines were slower relative to males in Hispanic and non-Hispanic (NH) Black individuals (2.3- and 1.08-fold difference, respectively), whereas NH White females declined 1.3-fold faster than males. Among Asian females, NSCLC incidence did not decline, and LUAD increased through 2017 (+2.45%) and remained stable in Hispanic females. In high-smoking states, male rates declined steadily (−4.32%), whereas female rates were stable until 2010, then dropped sharply, and converged with males by 2021. In low-smoking states, male rates declined 48.75% faster than female rates (−4.76% vs. −3.20%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Early-onset lung cancer incidence declined overall from 2000 to 2021, except for persistent or rising LUAD among Asian and Hispanic females, which implicates emerging non-tobacco risk factors and highlights the need for targeted prevention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"132 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145825423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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