Kajal Biswas,Sagar Ghosh,Payal P Khincha,Taylor Sundby,Anju Singh,Grace Ault,Mark Henderson,Andrea M Gross,Martha Donoghue,Sharon A Savage,Brigitte C Widemann,Robert H Shoemaker,Altaf Mohammed
In aggregate, rare cancers are not so rare as they collectively represent about one-fourth of all cancer cases. As defined by the National Cancer Institute (NCI), rare cancers are those that affect fewer than 15 people per 100,000 individuals annually. Research on this wide spectrum of malignancies has been limited, often due to their rarity. Survival rates for many rare cancers are worse than for more common cancers. To address many of the issues that impact the advancement of prevention/interception research for rare cancers, the NCI and the Department of Defense (DoD) hosted a two-day virtual workshop in May 2024. Key stakeholders, including scientists, clinicians, and patient advocates from across the United States, Canada, and the United Kingdom, came together to identify critical research gaps in rare cancers, address approaches for prevention, and discuss the emerging opportunities in the field. Participants engaged in an open discussion, exploring and promoting the prospects to further research on rare cancer prevention and interception. This article addresses the major challenges associated with rare cancers research and outlines potential strategies to advance efforts in the prevention and interception of rare cancers.
{"title":"Rare cancers research: Current state of knowledge and emerging opportunities for prevention and interception.","authors":"Kajal Biswas,Sagar Ghosh,Payal P Khincha,Taylor Sundby,Anju Singh,Grace Ault,Mark Henderson,Andrea M Gross,Martha Donoghue,Sharon A Savage,Brigitte C Widemann,Robert H Shoemaker,Altaf Mohammed","doi":"10.1093/jnci/djag068","DOIUrl":"https://doi.org/10.1093/jnci/djag068","url":null,"abstract":"In aggregate, rare cancers are not so rare as they collectively represent about one-fourth of all cancer cases. As defined by the National Cancer Institute (NCI), rare cancers are those that affect fewer than 15 people per 100,000 individuals annually. Research on this wide spectrum of malignancies has been limited, often due to their rarity. Survival rates for many rare cancers are worse than for more common cancers. To address many of the issues that impact the advancement of prevention/interception research for rare cancers, the NCI and the Department of Defense (DoD) hosted a two-day virtual workshop in May 2024. Key stakeholders, including scientists, clinicians, and patient advocates from across the United States, Canada, and the United Kingdom, came together to identify critical research gaps in rare cancers, address approaches for prevention, and discuss the emerging opportunities in the field. Participants engaged in an open discussion, exploring and promoting the prospects to further research on rare cancer prevention and interception. This article addresses the major challenges associated with rare cancers research and outlines potential strategies to advance efforts in the prevention and interception of rare cancers.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147383209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyeyeun Lim,Jinyoung Byun,Robert T Ripley,Jiyeon Choi,Chao Cheng,Aaron P Thrift,Younghun Han,Christopher I Amos
INTRODUCTIONLung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the two major histologic subtypes of non-small cell lung cancer and differ in prognosis, biological behavior, and molecular characteristics. Although aberrant DNA methylation has been implicated in lung cancer and patient survival, systematic investigations of subtype-specific methylation signatures distinguishing these subtypes remain limited.METHODSWe identified DNA methylation signatures that distinguish LUSC from LUAD and evaluated their associations with survival among ever-smokers using data from The Cancer Genome Atlas, with independent validation in the CURELUNG cohort. Survival analyses assessed associations between a methylation-based score and patient survival. Integrative analyses incorporating mRNA expression, global proteomic profiles, and transcription factor (TF) motifs enrichment were performed to explore potential regulatory features associated with the identified methylation markers.RESULTSEleven differentially methylated CpG sites distinguished LUSC and LUAD and demonstrated high classification accuracy in an independent validation cohort. Among LUSC cases, lower methylation scores (below the median) were associated with a 2.7-fold increased risk of mortality during the first two years of follow-up based on piecewise Cox regression models. Integrative analyses revealed subtype-specific differences in CALML3 expression and enrichment of TF binding motifs near the identified signatures, particularly C2H2 zinc-finger motifs.CONCLUSIONThis study identified a subtype-specific DNA methylation signature that robustly distinguishes LUAD and LUSC and is associated with early survival among ever-smokers with LUSC. These findings highlight biologically meaningful epigenetic patterns that may contribute to histology-specific tumor behavior and provide a foundation for future mechanistic and biomarker development studies.
{"title":"Methylation signatures distinguish non small cell lung cancer subtypes and associated with survival in smokers with lung squamous cell carcinoma.","authors":"Hyeyeun Lim,Jinyoung Byun,Robert T Ripley,Jiyeon Choi,Chao Cheng,Aaron P Thrift,Younghun Han,Christopher I Amos","doi":"10.1093/jnci/djag067","DOIUrl":"https://doi.org/10.1093/jnci/djag067","url":null,"abstract":"INTRODUCTIONLung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the two major histologic subtypes of non-small cell lung cancer and differ in prognosis, biological behavior, and molecular characteristics. Although aberrant DNA methylation has been implicated in lung cancer and patient survival, systematic investigations of subtype-specific methylation signatures distinguishing these subtypes remain limited.METHODSWe identified DNA methylation signatures that distinguish LUSC from LUAD and evaluated their associations with survival among ever-smokers using data from The Cancer Genome Atlas, with independent validation in the CURELUNG cohort. Survival analyses assessed associations between a methylation-based score and patient survival. Integrative analyses incorporating mRNA expression, global proteomic profiles, and transcription factor (TF) motifs enrichment were performed to explore potential regulatory features associated with the identified methylation markers.RESULTSEleven differentially methylated CpG sites distinguished LUSC and LUAD and demonstrated high classification accuracy in an independent validation cohort. Among LUSC cases, lower methylation scores (below the median) were associated with a 2.7-fold increased risk of mortality during the first two years of follow-up based on piecewise Cox regression models. Integrative analyses revealed subtype-specific differences in CALML3 expression and enrichment of TF binding motifs near the identified signatures, particularly C2H2 zinc-finger motifs.CONCLUSIONThis study identified a subtype-specific DNA methylation signature that robustly distinguishes LUAD and LUSC and is associated with early survival among ever-smokers with LUSC. These findings highlight biologically meaningful epigenetic patterns that may contribute to histology-specific tumor behavior and provide a foundation for future mechanistic and biomarker development studies.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147383211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael A O'Rorke,Tao Xu,Rhonda R Decook,Bradley D Mcdowell,Brian M Gryzlak,Nicholas J Rudzianski,Kimberly C Serrano,Abigayle M Wehrheim,Udhayvir S Grewal,Chandrikha Chandrasekharan,Joseph S Dillon,Thorvardur R Halfdanarson,T Clark Gamblin,Lindsay G Cowell,Tobias Else,Heloisa P Soares,Vineeth Sukrithan,Sravani Chandaka,Hanna K Sanoff,Fiona C He,David Geller,Robert A Ramirez,Mei Liu,William Lancaster,Josh A Mailman,Heather Moran,Maryann Wahmann,Elyse Gellerman,Elizabeth A Chrischilles,
BACKGROUNDNeuroendocrine tumors (NETs) are rare, heterogeneous neoplasms associated with prolonged survival and substantial symptom burden. However, patient-reported outcomes (PROs) across NET subtypes remain poorly characterized, particularly in real-world settings. This study describes baseline health-related quality of life (HRQoL) and care experiences among patients with gastroenteropancreatic (GEP) and lung NETs, examining differences by tumor site and time since diagnosis.METHODSThe Neuroendocrine Tumors-Patient Reported Outcomes (NET-PRO) study is a prospective, multi-institutional U.S. cohort of adults (≥18 years) with incident small intestinal (SI-NET), pancreatic (pNET), GEP, or lung NETs diagnosed from January 2018 through September 2024, identified via a validated electronic medical record (EMR)-based computable phenotype. Baseline surveys assessed HRQoL, symptoms, care experiences, and clinical characteristics using validated instruments. Descriptive statistics and standardized mean differences (SMDs) compared responses by NET site and time since diagnosis.RESULTSAmong 2,367 participants (mean age 57.8 years; 57.3% female), 1,974 had GEP-NETs (659 SI-NET, 555 pNET) and 393 had lung NETs. Fatigue (mean 33.0), insomnia (32.5), and diarrhea (25.7) were the most burdensome symptoms. Lung NET patients reported worse dyspnea (SMD = 0.58, p < 0.001) and lower physical, role, and global QoL scores than those with GEP-NETs, while pNET patients reported better functioning. Diarrhea worsened over time, especially in SI-NETs. Most rated care highly (75.3%) but cited concerns about treatment side effects (80.4%), costs (60.7%), and travel burden (58.8%).CONCLUSIONSThis large U.S. cohort reveals persistent symptom burden and HRQoL variation by tumor site and disease duration, underscoring the need for longitudinal HRQoL assessment in NET care.
{"title":"Quality of life and care experiences in a US multi-institutional neuroendocrine tumor cohort.","authors":"Michael A O'Rorke,Tao Xu,Rhonda R Decook,Bradley D Mcdowell,Brian M Gryzlak,Nicholas J Rudzianski,Kimberly C Serrano,Abigayle M Wehrheim,Udhayvir S Grewal,Chandrikha Chandrasekharan,Joseph S Dillon,Thorvardur R Halfdanarson,T Clark Gamblin,Lindsay G Cowell,Tobias Else,Heloisa P Soares,Vineeth Sukrithan,Sravani Chandaka,Hanna K Sanoff,Fiona C He,David Geller,Robert A Ramirez,Mei Liu,William Lancaster,Josh A Mailman,Heather Moran,Maryann Wahmann,Elyse Gellerman,Elizabeth A Chrischilles, ","doi":"10.1093/jnci/djag069","DOIUrl":"https://doi.org/10.1093/jnci/djag069","url":null,"abstract":"BACKGROUNDNeuroendocrine tumors (NETs) are rare, heterogeneous neoplasms associated with prolonged survival and substantial symptom burden. However, patient-reported outcomes (PROs) across NET subtypes remain poorly characterized, particularly in real-world settings. This study describes baseline health-related quality of life (HRQoL) and care experiences among patients with gastroenteropancreatic (GEP) and lung NETs, examining differences by tumor site and time since diagnosis.METHODSThe Neuroendocrine Tumors-Patient Reported Outcomes (NET-PRO) study is a prospective, multi-institutional U.S. cohort of adults (≥18 years) with incident small intestinal (SI-NET), pancreatic (pNET), GEP, or lung NETs diagnosed from January 2018 through September 2024, identified via a validated electronic medical record (EMR)-based computable phenotype. Baseline surveys assessed HRQoL, symptoms, care experiences, and clinical characteristics using validated instruments. Descriptive statistics and standardized mean differences (SMDs) compared responses by NET site and time since diagnosis.RESULTSAmong 2,367 participants (mean age 57.8 years; 57.3% female), 1,974 had GEP-NETs (659 SI-NET, 555 pNET) and 393 had lung NETs. Fatigue (mean 33.0), insomnia (32.5), and diarrhea (25.7) were the most burdensome symptoms. Lung NET patients reported worse dyspnea (SMD = 0.58, p < 0.001) and lower physical, role, and global QoL scores than those with GEP-NETs, while pNET patients reported better functioning. Diarrhea worsened over time, especially in SI-NETs. Most rated care highly (75.3%) but cited concerns about treatment side effects (80.4%), costs (60.7%), and travel burden (58.8%).CONCLUSIONSThis large U.S. cohort reveals persistent symptom burden and HRQoL variation by tumor site and disease duration, underscoring the need for longitudinal HRQoL assessment in NET care.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"267 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147383210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advance care planning and caregiver outcomes in advanced cancer: an essential metric of success.","authors":"Elise C Carey,Jacob J Strand","doi":"10.1093/jnci/djaf382","DOIUrl":"https://doi.org/10.1093/jnci/djaf382","url":null,"abstract":"","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147383212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Social factors influence cancer trial participation: can digital interventions help close the disparities gap?","authors":"Sarah Nechuta,Theresa Bacon-Baguley,Lauren Hamel","doi":"10.1093/jnci/djag040","DOIUrl":"https://doi.org/10.1093/jnci/djag040","url":null,"abstract":"","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"From promise to proof: reference sets for validation of multicancer early detection.","authors":"Peter Sasieni,Jonathan C M Wan,Matejka Rebolj","doi":"10.1093/jnci/djag031","DOIUrl":"https://doi.org/10.1093/jnci/djag031","url":null,"abstract":"","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"253 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jennifer Rogers,Michael Michael,Jeanne Tie,Benjamin J Solomon,Sam Harris,Craig Underhill,Rory Wolfe,Kate Burbury,Marliese Alexander
Thromboembolism (TE) is a major cause of early mortality in cancer. TARGET-TP randomised high-risk patients with lung or gastrointestinal cancers, identified using a d-dimer/fibrinogen model, to enoxaparin or no thromboprophylaxis; low-risk patients were observed. Thromboprophylaxis reduced TE and 6-month mortality. This study reports extended overall survival (OS) and progression-free survival (PFS) to 36 months. Among high-risk patients, thromboprophylaxis improved OS at 6 and 12 months, with convergence thereafter; no PFS differences were observed. Adjustment for on-study TE attenuated the OS effect, consistent with thrombosis-specific risk reduction. These findings describe the duration and extent of survival benefit achievable with biomarker-guided thromboprophylaxis and highlight that TARGET-TP is the first trial to demonstrate a survival advantage, likely driven by cohort enrichment for thrombotic risk. The improved risk-benefit profile supports real-world evaluation of d-dimer/fibrinogen-guided thromboprophylaxis in lung and gastrointestinal cancers, with validation of the model warranted in additional tumour groups.
{"title":"Long-term survival outcomes after biomarker-guided thromboprophylaxis in cancer: extended follow-up of the TARGET-TP randomised trial.","authors":"Jennifer Rogers,Michael Michael,Jeanne Tie,Benjamin J Solomon,Sam Harris,Craig Underhill,Rory Wolfe,Kate Burbury,Marliese Alexander","doi":"10.1093/jnci/djag065","DOIUrl":"https://doi.org/10.1093/jnci/djag065","url":null,"abstract":"Thromboembolism (TE) is a major cause of early mortality in cancer. TARGET-TP randomised high-risk patients with lung or gastrointestinal cancers, identified using a d-dimer/fibrinogen model, to enoxaparin or no thromboprophylaxis; low-risk patients were observed. Thromboprophylaxis reduced TE and 6-month mortality. This study reports extended overall survival (OS) and progression-free survival (PFS) to 36 months. Among high-risk patients, thromboprophylaxis improved OS at 6 and 12 months, with convergence thereafter; no PFS differences were observed. Adjustment for on-study TE attenuated the OS effect, consistent with thrombosis-specific risk reduction. These findings describe the duration and extent of survival benefit achievable with biomarker-guided thromboprophylaxis and highlight that TARGET-TP is the first trial to demonstrate a survival advantage, likely driven by cohort enrichment for thrombotic risk. The improved risk-benefit profile supports real-world evaluation of d-dimer/fibrinogen-guided thromboprophylaxis in lung and gastrointestinal cancers, with validation of the model warranted in additional tumour groups.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147373830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Grace Lu-Yao,Nikita Nikita,Scott W Keith,Krupa Gandhi,Amy L Shaver,Swapnil Sharma,Christina Steinbock-Malfer,Hushan Yang,Christopher Yang,Kevin K Zarrabi,Stephen J Freedland,William K Kelly
BACKGROUNDThis population-based study aimed to quantify fracture risk after ARPIs in PCa patients by pre-existing health conditions.PATIENTS AND METHODSPatients were identified from the SEER-Medicare files who received abiraterone with prednisone (AAP) or enzalutamide (ENZA) between 1/1/2013 and 12/31/2020. Health and fracture history were based on claims one year before ARPI with follow-up through 12/31/2020. The main outcome of the study was the cumulative fracture risk after first date of ARPI. Fine and Gray's sub-distribution hazard model was used to obtain adjusted relative risks with confounding factors.RESULTSThis study included 10,463 patients (6,037- AAP; 4,426-ENZA). The 3-year fracture risk after ARPI was high, exceeding 25% among those without a prior fracture. Among 1,445 men with a fracture the year before ARPI, 3-year fracture risk exceeded 50%, and remained high (above 44%) despite using bone health agents (BHA). A recent history of fracture was associated with a 2.84-fold fracture risk (aHR: 2.84, 95% CI 2.58-3.12). Pre-existing osteoporosis and a comorbidity score ≥ 2 were associated with 15% (aHR : 1.15, 95% CI 1.03-1.29) and 11% (aHR : 1.11, 95% CI 1.00 to 1.24) higher fracture risks. Bone health agent (BHA) use was associated with a 23% lower fracture risk (aHR: 0.77, 95% CI 0.70-0.83).CONCLUSIONFracture risk after ARPI was high, exceeding 44% within 3 years in those with prior fractures despite BHA, suggesting limited benefit in patients with poor bone quality. Early identification and intervention for patients at high risk of fractures is critical.
背景：这项以人群为基础的研究旨在量化前列腺癌患者在arpi后的骨折风险。患者和方法从SEER-Medicare档案中确定在2013年1月1日至2020年12月31日期间接受阿比特龙合并强的松（AAP）或恩杂鲁胺（ENZA）治疗的患者。健康和骨折史基于ARPI前一年的索赔，随访至2020年12月31日。该研究的主要结果是ARPI首次日期后的累积骨折风险。采用Fine and Gray的亚分布风险模型，得到考虑混杂因素的调整后的相对风险。结果纳入10463例患者（6037例为AAP， 4426例为enza）。ARPI术后3年骨折风险高，在无骨折史的患者中超过25%。在ARPI前一年发生骨折的1445名男性中，3年骨折风险超过50%，尽管使用了骨骼健康剂（BHA），但仍然很高（超过44%）。近期骨折史与2.84倍的骨折风险相关（aHR: 2.84, 95% CI 2.58-3.12）。先前存在的骨质疏松症和合并症评分≥2与骨折风险增加15% （aHR: 1.15, 95% CI 1.03-1.29）和11% （aHR: 1.11, 95% CI 1.00 - 1.24）相关。骨健康剂（BHA）的使用与骨折风险降低23%相关（aHR: 0.77, 95% CI 0.70-0.83）。结论ARPI术后骨折风险较高，有BHA的患者3年内骨折风险超过44%，对骨质量较差的患者获益有限。骨折高危患者的早期识别和干预至关重要。
{"title":"Risk of fracture following androgen receptor pathway inhibitors in men with advanced prostate cancer.","authors":"Grace Lu-Yao,Nikita Nikita,Scott W Keith,Krupa Gandhi,Amy L Shaver,Swapnil Sharma,Christina Steinbock-Malfer,Hushan Yang,Christopher Yang,Kevin K Zarrabi,Stephen J Freedland,William K Kelly","doi":"10.1093/jnci/djag061","DOIUrl":"https://doi.org/10.1093/jnci/djag061","url":null,"abstract":"BACKGROUNDThis population-based study aimed to quantify fracture risk after ARPIs in PCa patients by pre-existing health conditions.PATIENTS AND METHODSPatients were identified from the SEER-Medicare files who received abiraterone with prednisone (AAP) or enzalutamide (ENZA) between 1/1/2013 and 12/31/2020. Health and fracture history were based on claims one year before ARPI with follow-up through 12/31/2020. The main outcome of the study was the cumulative fracture risk after first date of ARPI. Fine and Gray's sub-distribution hazard model was used to obtain adjusted relative risks with confounding factors.RESULTSThis study included 10,463 patients (6,037- AAP; 4,426-ENZA). The 3-year fracture risk after ARPI was high, exceeding 25% among those without a prior fracture. Among 1,445 men with a fracture the year before ARPI, 3-year fracture risk exceeded 50%, and remained high (above 44%) despite using bone health agents (BHA). A recent history of fracture was associated with a 2.84-fold fracture risk (aHR: 2.84, 95% CI 2.58-3.12). Pre-existing osteoporosis and a comorbidity score ≥ 2 were associated with 15% (aHR : 1.15, 95% CI 1.03-1.29) and 11% (aHR : 1.11, 95% CI 1.00 to 1.24) higher fracture risks. Bone health agent (BHA) use was associated with a 23% lower fracture risk (aHR: 0.77, 95% CI 0.70-0.83).CONCLUSIONFracture risk after ARPI was high, exceeding 44% within 3 years in those with prior fractures despite BHA, suggesting limited benefit in patients with poor bone quality. Early identification and intervention for patients at high risk of fractures is critical.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"236 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147373831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yashasvini Sampathkumar,Ziad Zakaria,Kelli O'Connell,Jenna Bhimani,Victoria S Blinder,Rachael Burganowski,Isaac J Ergas,Grace B Gallagher,Jennifer J Griggs,Narre Heon,Tatjana Kolevska,Yuriy Kotsurovskyy,Candyce H Kroenke,Cecile A Laurent,Raymond Liu,Maria J Monroy-Iglesias,Kanichi G Nakata,Sonia Persaud,Janise M Roh,Sara Tabatabai,Emily Valice,Peng Wang,Elisa V Bandera,Erin J Aiello Bowles,Lawrence H Kushi,Elizabeth D Kantor
BACKGROUNDChemotherapy dose reductions are associated with poorer survival. To better understand the role of clinician- and facility-level factors in chemotherapy dosing, we conducted an analysis within a large, real-world cohort of women with stages I-IIIA breast cancer.METHODSOur cohort included 8,540 breast cancer patients receiving chemotherapy at Kaiser Permanente Northern California between 2006 and 2019. Patients were treated across 22 facilities by 198 clinicians. We evaluated associations between clinician- and facility-level factors related to dose reductions at the start of chemotherapy (first cycle dose proportion, FCDP, <90%) and throughout treatment (average relative dose intensity, ARDI, <90%). Prevalence ratios (PR) and corresponding 95% confidence intervals (CI) were estimated for the clinician and facility factors in relation to chemotherapy dose reductions.RESULTSFactors associated with an increased likelihood of dose reduction were increased clinician years since medical school (FCDP < 90%: PR≥30 vs <10 years : 1.78, p-trend = 0.03; ARDI < 90%: PR≥30 vs <10 years : 1.29, p-trend = 0.03) and treatment at less urban facilities (ARDI < 90%: PR<100% vs 100% urban : 1.38, p-trend = 0.002). Factors associated with a decreased likelihood of dose reduction were higher annual clinician volume of stages I-IIIA breast cancer patients (FCDP < 90%: PR≥30 vs ≤15 patients : 0.64, p-trend = 0.03; ARDI < 90%: PR≥30 vs ≤15 patients : 0.76, p-trend = 0.01), higher treatment facility annual volume of stages I-IIIA breast cancer patients (ARDI < 90%: PR≥200 vs <75 patients : 0.85, p-trend = 0.03), and a larger practice size (FCDP < 90%: PR≥10 vs ≤5 oncologists : 0.53, p-trend = 0.02).CONCLUSIONSClinician- and facility-level factors were associated with chemotherapy dose reductions. Practice-level changes, such as increasing breast cancer patient volumes and practice size, may support optimal dosing practices.
{"title":"Clinician- and facility-level factors associated with chemotherapy dose reductions in stages I-IIIA breast cancer.","authors":"Yashasvini Sampathkumar,Ziad Zakaria,Kelli O'Connell,Jenna Bhimani,Victoria S Blinder,Rachael Burganowski,Isaac J Ergas,Grace B Gallagher,Jennifer J Griggs,Narre Heon,Tatjana Kolevska,Yuriy Kotsurovskyy,Candyce H Kroenke,Cecile A Laurent,Raymond Liu,Maria J Monroy-Iglesias,Kanichi G Nakata,Sonia Persaud,Janise M Roh,Sara Tabatabai,Emily Valice,Peng Wang,Elisa V Bandera,Erin J Aiello Bowles,Lawrence H Kushi,Elizabeth D Kantor","doi":"10.1093/jnci/djag063","DOIUrl":"https://doi.org/10.1093/jnci/djag063","url":null,"abstract":"BACKGROUNDChemotherapy dose reductions are associated with poorer survival. To better understand the role of clinician- and facility-level factors in chemotherapy dosing, we conducted an analysis within a large, real-world cohort of women with stages I-IIIA breast cancer.METHODSOur cohort included 8,540 breast cancer patients receiving chemotherapy at Kaiser Permanente Northern California between 2006 and 2019. Patients were treated across 22 facilities by 198 clinicians. We evaluated associations between clinician- and facility-level factors related to dose reductions at the start of chemotherapy (first cycle dose proportion, FCDP, <90%) and throughout treatment (average relative dose intensity, ARDI, <90%). Prevalence ratios (PR) and corresponding 95% confidence intervals (CI) were estimated for the clinician and facility factors in relation to chemotherapy dose reductions.RESULTSFactors associated with an increased likelihood of dose reduction were increased clinician years since medical school (FCDP < 90%: PR≥30 vs <10 years : 1.78, p-trend = 0.03; ARDI < 90%: PR≥30 vs <10 years : 1.29, p-trend = 0.03) and treatment at less urban facilities (ARDI < 90%: PR<100% vs 100% urban : 1.38, p-trend = 0.002). Factors associated with a decreased likelihood of dose reduction were higher annual clinician volume of stages I-IIIA breast cancer patients (FCDP < 90%: PR≥30 vs ≤15 patients : 0.64, p-trend = 0.03; ARDI < 90%: PR≥30 vs ≤15 patients : 0.76, p-trend = 0.01), higher treatment facility annual volume of stages I-IIIA breast cancer patients (ARDI < 90%: PR≥200 vs <75 patients : 0.85, p-trend = 0.03), and a larger practice size (FCDP < 90%: PR≥10 vs ≤5 oncologists : 0.53, p-trend = 0.02).CONCLUSIONSClinician- and facility-level factors were associated with chemotherapy dose reductions. Practice-level changes, such as increasing breast cancer patient volumes and practice size, may support optimal dosing practices.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kirsten M Woolpert, Anders Kjærsgaard, Lidia Schapira, Henrik Toft Sørensen, Deirdre Cronin-Fenton
Background Pain is a common long-lasting effect of breast cancer treatment. However, adequate pain management can be a challenge in survivorship care. Opioids remain important for acute and chronic pain, yet prolonged use carries risks of dependence and overdose. Denmark has historically had high opioid prescription rates, but the duration, strength, and intensity of use among breast cancer survivors is not well described. Methods We conducted a nationwide registry-based study of 84,610 Danish women diagnosed with stage I–III breast cancer (1997 − 2020). We described temporal trends in opioid-prescribing and examined associations between sociodemographic and clinical characteristics and five potentially harmful opioid-related outcomes after breast cancer new and prolonged use, long-term use, long-term strong use, concurrent use with sedative-hypnotics, and diagnosed substance-related disorder or overdose. Results Within one year of diagnosis, 18% of women filled at least one opioid prescription; this proportion declined steadily after 2015. Codeine, the most common initial opioid in the late 1990s, was gradually replaced by tramadol, morphine, and oxycodone. Across the cohort, 6.1% had long-term use, 2.0% long-term strong use, 3.6% concurrent opioid and sedative-hypnotic use, and 0.4% developed an substance-related disorder or overdose. Among 74,771 opioid-naïve patients, 1.7% became new and prolonged users. Odds of these opioid-related behaviors were higher among women with socioeconomic hardships, psychiatric morbidity, comorbidity, and advanced disease. Discussion Opioid use after breast cancer was uncommon and declined over time in Denmark. Nonetheless, social and clinical disparities persisted, highlighting the importance of survivorship care that balances safe prescribing with adequate pain management.
{"title":"Opioid use after breast cancer in Denmark: a nationwide study of social and clinical factors","authors":"Kirsten M Woolpert, Anders Kjærsgaard, Lidia Schapira, Henrik Toft Sørensen, Deirdre Cronin-Fenton","doi":"10.1093/jnci/djag052","DOIUrl":"https://doi.org/10.1093/jnci/djag052","url":null,"abstract":"Background Pain is a common long-lasting effect of breast cancer treatment. However, adequate pain management can be a challenge in survivorship care. Opioids remain important for acute and chronic pain, yet prolonged use carries risks of dependence and overdose. Denmark has historically had high opioid prescription rates, but the duration, strength, and intensity of use among breast cancer survivors is not well described. Methods We conducted a nationwide registry-based study of 84,610 Danish women diagnosed with stage I–III breast cancer (1997 − 2020). We described temporal trends in opioid-prescribing and examined associations between sociodemographic and clinical characteristics and five potentially harmful opioid-related outcomes after breast cancer new and prolonged use, long-term use, long-term strong use, concurrent use with sedative-hypnotics, and diagnosed substance-related disorder or overdose. Results Within one year of diagnosis, 18% of women filled at least one opioid prescription; this proportion declined steadily after 2015. Codeine, the most common initial opioid in the late 1990s, was gradually replaced by tramadol, morphine, and oxycodone. Across the cohort, 6.1% had long-term use, 2.0% long-term strong use, 3.6% concurrent opioid and sedative-hypnotic use, and 0.4% developed an substance-related disorder or overdose. Among 74,771 opioid-naïve patients, 1.7% became new and prolonged users. Odds of these opioid-related behaviors were higher among women with socioeconomic hardships, psychiatric morbidity, comorbidity, and advanced disease. Discussion Opioid use after breast cancer was uncommon and declined over time in Denmark. Nonetheless, social and clinical disparities persisted, highlighting the importance of survivorship care that balances safe prescribing with adequate pain management.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"128 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147287364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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