Background: Total neoadjuvant therapy (TNT) is a preferred method for the treatment of locally advanced rectal cancer (LARC). Two techniques of radiotherapy have been used in TNT trials so far, including long-course chemoradiotherapy (LCRT) and short-course radiotherapy (SCRT). However, to date, no study compares these techniques in a head-to-head fashion. Our objective is to compare the complete clinical response among patients with LARC who receive long or short-course radiation therapy in combination with the same chemotherapy regimen.
Methods: 158 patients (18-80 years old) with standard or high-risk LARC (T3/T4 tumor or lymph node positive) located at least 5 cm from the anal verge will be randomized into two groups: LCRT (with a dose of 50.4 Gy in 28 sessions) or SCRT (with a dose of 25 Gy in five sessions). Both of these groups will receive concurrent chemotherapy (capecitabine 825 mg/m2 twice daily) followed by consolidation chemotherapy with the CAPEOX regimen for 6 cycles or mFOLFOX7 for 9 cycles. We will compare the complete clinical response (initially 12-16 weeks after the last RT fraction and eventually 2 weeks after the last chemotherapy cycle) by MRI as the primary endpoint. Overall survival (OS), metastasis-free survival (MFS), local control, and toxicities will be evaluated after 3-5 years as the secondary endpoints.
Discussion: Advances in the treatment of rectal cancer focus on metastasis control, besides local control by using neoadjuvant therapy. Determining the complete clinical response, OS, and MFS of short-course versus long-course chemoradiation will assist in choosing the best LARC treatment protocol.
{"title":"Comparison of the Clinical Response in Total Neoadjuvant Treatment With Long-Term or Short-Term Chemoradiotherapy Followed by Consolidation Chemotherapy in Patients With Locally Advanced Rectal Cancer (TEHRAN); the Protocol for a Randomized Controlled Clinical Trial.","authors":"Mahdi Aghili, Reza Ghalehtaki, Mahdiyeh Yaghooti-Khorasani, Seyed Masoud Miratashi Yazdi, Kasra Kolahdouzan","doi":"10.1002/cam4.71472","DOIUrl":"10.1002/cam4.71472","url":null,"abstract":"<p><strong>Background: </strong>Total neoadjuvant therapy (TNT) is a preferred method for the treatment of locally advanced rectal cancer (LARC). Two techniques of radiotherapy have been used in TNT trials so far, including long-course chemoradiotherapy (LCRT) and short-course radiotherapy (SCRT). However, to date, no study compares these techniques in a head-to-head fashion. Our objective is to compare the complete clinical response among patients with LARC who receive long or short-course radiation therapy in combination with the same chemotherapy regimen.</p><p><strong>Methods: </strong>158 patients (18-80 years old) with standard or high-risk LARC (T3/T4 tumor or lymph node positive) located at least 5 cm from the anal verge will be randomized into two groups: LCRT (with a dose of 50.4 Gy in 28 sessions) or SCRT (with a dose of 25 Gy in five sessions). Both of these groups will receive concurrent chemotherapy (capecitabine 825 mg/m<sup>2</sup> twice daily) followed by consolidation chemotherapy with the CAPEOX regimen for 6 cycles or mFOLFOX7 for 9 cycles. We will compare the complete clinical response (initially 12-16 weeks after the last RT fraction and eventually 2 weeks after the last chemotherapy cycle) by MRI as the primary endpoint. Overall survival (OS), metastasis-free survival (MFS), local control, and toxicities will be evaluated after 3-5 years as the secondary endpoints.</p><p><strong>Discussion: </strong>Advances in the treatment of rectal cancer focus on metastasis control, besides local control by using neoadjuvant therapy. Determining the complete clinical response, OS, and MFS of short-course versus long-course chemoradiation will assist in choosing the best LARC treatment protocol.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT05920928, 2023.06.27.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 24","pages":"e71472"},"PeriodicalIF":3.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12714538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145779807","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}
Alexander J Didier, Charlotte Lennox, Mingjia Li, Jinesh Gheeya, Asrar Alahmadi, Jacob Kaufman, Regan Memmott, Kai He, Peter Shields, Christian Rolfo, David P Carbone, Carolyn Presley, Dwight Owen, Logan Roof
Introduction: Pleural mesothelioma (PM) is a rare, aggressive cancer with significant variation in incidence based on geographic factors. Previous studies have highlighted cancer survival disparities between metropolitan and nonmetropolitan populations for other cancers; this data is largely unreported for PM. We aimed to compare incidence trends and cancer-specific survival (CSS) between metropolitan and nonmetropolitan areas in the United States using the Surveillance, Epidemiology, and End Results (SEER) database.
Methods: We analyzed SEER 18 registries for patients aged ≥ 20 diagnosed with PM between 2004 and 2021. Incidence rates, CSS, and demographic and clinical characteristics were compared between metropolitan and nonmetropolitan areas. Incidence rate ratios (IRRs) were calculated using the Tiwari method. Joinpoint regression was used to assess temporal trends, while Kaplan-Meier and Cox proportional hazard models analyzed survival outcomes.
Results: A total of 8519 PM cases were identified, with 89.3% in metropolitan areas. Nonmetropolitan patients were more likely to be non-Hispanic Black and had lower chemotherapy (p = 0.031) and surgery (p < 0.001) rates. The incidence rate in metropolitan areas declined from 1.4 in 2004 to 0.8 in 2021, while nonmetropolitan areas saw a stable incidence until 2017, followed by a decline to 0.5 in 2021. Metropolitan areas had significantly higher CSS, with 50.3% 1-year CSS by 2020, compared to 27.7% in nonmetropolitan areas. Multivariate analysis indicated a higher hazard of death in nonmetropolitan areas (HR = 1.18, p < 0.001).
Conclusion: Significant disparities in PM outcomes between metropolitan and nonmetropolitan areas were revealed. Although both regions experienced a decline in incidence over time, survival outcomes remained worse in nonmetropolitan areas. Patients in nonmetropolitan areas were also less likely to receive chemotherapy and surgery, further contributing to the survival gap. These findings highlight the need for targeted interventions to improve treatment access and enhance survival for nonmetropolitan patients with PM.
{"title":"Trends in Pleural Mesothelioma Incidence and Survival in Metropolitan and Nonmetropolitan Areas in the United States.","authors":"Alexander J Didier, Charlotte Lennox, Mingjia Li, Jinesh Gheeya, Asrar Alahmadi, Jacob Kaufman, Regan Memmott, Kai He, Peter Shields, Christian Rolfo, David P Carbone, Carolyn Presley, Dwight Owen, Logan Roof","doi":"10.1002/cam4.71474","DOIUrl":"10.1002/cam4.71474","url":null,"abstract":"<p><strong>Introduction: </strong>Pleural mesothelioma (PM) is a rare, aggressive cancer with significant variation in incidence based on geographic factors. Previous studies have highlighted cancer survival disparities between metropolitan and nonmetropolitan populations for other cancers; this data is largely unreported for PM. We aimed to compare incidence trends and cancer-specific survival (CSS) between metropolitan and nonmetropolitan areas in the United States using the Surveillance, Epidemiology, and End Results (SEER) database.</p><p><strong>Methods: </strong>We analyzed SEER 18 registries for patients aged ≥ 20 diagnosed with PM between 2004 and 2021. Incidence rates, CSS, and demographic and clinical characteristics were compared between metropolitan and nonmetropolitan areas. Incidence rate ratios (IRRs) were calculated using the Tiwari method. Joinpoint regression was used to assess temporal trends, while Kaplan-Meier and Cox proportional hazard models analyzed survival outcomes.</p><p><strong>Results: </strong>A total of 8519 PM cases were identified, with 89.3% in metropolitan areas. Nonmetropolitan patients were more likely to be non-Hispanic Black and had lower chemotherapy (p = 0.031) and surgery (p < 0.001) rates. The incidence rate in metropolitan areas declined from 1.4 in 2004 to 0.8 in 2021, while nonmetropolitan areas saw a stable incidence until 2017, followed by a decline to 0.5 in 2021. Metropolitan areas had significantly higher CSS, with 50.3% 1-year CSS by 2020, compared to 27.7% in nonmetropolitan areas. Multivariate analysis indicated a higher hazard of death in nonmetropolitan areas (HR = 1.18, p < 0.001).</p><p><strong>Conclusion: </strong>Significant disparities in PM outcomes between metropolitan and nonmetropolitan areas were revealed. Although both regions experienced a decline in incidence over time, survival outcomes remained worse in nonmetropolitan areas. Patients in nonmetropolitan areas were also less likely to receive chemotherapy and surgery, further contributing to the survival gap. These findings highlight the need for targeted interventions to improve treatment access and enhance survival for nonmetropolitan patients with PM.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 24","pages":"e71474"},"PeriodicalIF":3.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12704024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754878","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}
Jordyn A Brown, Taylor D Ellington, Leah Moubadder, Maya Bliss, Anjali D Kumar, Chantel L Martin, Laura Farnan, Adrian Gerstel, Lauren E McCullough, Hazel B Nichols
Background: Historical and contemporary mortgage lending practices have been associated with worse cancer outcomes. We estimated the association between mortgage loan denial risk and health-related quality of life (HRQoL) among survivors at a large tertiary medical center in North Carolina (NC).
Methods: Mortgage denial risk, calculated using Home Mortgage Disclosure Act data (2010-2014), was linked by census tract to UNC Cancer Survivorship Cohort survivors who resided within NC metropolitan statistical areas (MSAs). HRQoL was measured using the validated Functional Assessment of Cancer Therapy-General (FACT-G). Differences in well-being across seven MSAs were assessed using Pearson chi-square tests and modified Poisson regression models adjusted for demographic and socioeconomic characteristics.
Results: Over 40% of survivors reported low overall well-being, while more than one-third of survivors reported low physical, social, emotional, or functional well-being. FACT-G scores were 6.2 (95% CI: 1.5, 10.9) points lower among Greensboro survivors; 4.1 (95% CI: 0.1, 8.1) points lower among Fayetteville MSA survivors; and 9.6 (95% CI: 2.5, 16.8) points lower among Charlotte survivors at a higher risk for mortgage loan denial compared to those at lower risk. Racial differences in FACT-G scores were only observed among Greensboro and Charlotte MSA survivors, whereas sex differences were limited to Charlotte survivors.
Conclusions: Mortgage loan denial was associated with worse overall HRQoL in Greensboro, Fayetteville, and Charlotte, but not in other NC MSAs. Further investigation into the role of place in other NC MSAs is needed to identify opportunities to support survivors across the cancer control continuum.
{"title":"Contemporary Area-Level Mortgage Loan Denial Risk and Health-Related Quality of Life Among Cancer Survivors.","authors":"Jordyn A Brown, Taylor D Ellington, Leah Moubadder, Maya Bliss, Anjali D Kumar, Chantel L Martin, Laura Farnan, Adrian Gerstel, Lauren E McCullough, Hazel B Nichols","doi":"10.1002/cam4.71433","DOIUrl":"10.1002/cam4.71433","url":null,"abstract":"<p><strong>Background: </strong>Historical and contemporary mortgage lending practices have been associated with worse cancer outcomes. We estimated the association between mortgage loan denial risk and health-related quality of life (HRQoL) among survivors at a large tertiary medical center in North Carolina (NC).</p><p><strong>Methods: </strong>Mortgage denial risk, calculated using Home Mortgage Disclosure Act data (2010-2014), was linked by census tract to UNC Cancer Survivorship Cohort survivors who resided within NC metropolitan statistical areas (MSAs). HRQoL was measured using the validated Functional Assessment of Cancer Therapy-General (FACT-G). Differences in well-being across seven MSAs were assessed using Pearson chi-square tests and modified Poisson regression models adjusted for demographic and socioeconomic characteristics.</p><p><strong>Results: </strong>Over 40% of survivors reported low overall well-being, while more than one-third of survivors reported low physical, social, emotional, or functional well-being. FACT-G scores were 6.2 (95% CI: 1.5, 10.9) points lower among Greensboro survivors; 4.1 (95% CI: 0.1, 8.1) points lower among Fayetteville MSA survivors; and 9.6 (95% CI: 2.5, 16.8) points lower among Charlotte survivors at a higher risk for mortgage loan denial compared to those at lower risk. Racial differences in FACT-G scores were only observed among Greensboro and Charlotte MSA survivors, whereas sex differences were limited to Charlotte survivors.</p><p><strong>Conclusions: </strong>Mortgage loan denial was associated with worse overall HRQoL in Greensboro, Fayetteville, and Charlotte, but not in other NC MSAs. Further investigation into the role of place in other NC MSAs is needed to identify opportunities to support survivors across the cancer control continuum.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 24","pages":"e71433"},"PeriodicalIF":3.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12710087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145766630","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}
Angelique Quartier, Ahmed Y. Sanin, Julia Nagelschmitz, Justine Schneider, Wenjie Shi, Thomas Wartmann, Maximilian Dölling, Frederike Stelter, Mihailo Andric, Roland S. Croner, Pierre Eftekhari, Ulf D. Kahlert
<div> <section> <h3> Background</h3> <p>Panitumumab shows limited clinical benefit in colorectal cancer (CRC), and reliable predictive biomarkers to guide patient selection remain lacking. To address this gap, we investigated molecular determinants of therapeutic response using tumor samples from patients with primary and metastatic CRC. By integrating PIMS-based metastatic classification, NPOT interaction profiling and quantitative proteomics, this study aimed to identify response-associated pathways and potential prognostic biomarkers that could support improved stratification for panitumumab therapy.</p> </section> <section> <h3> Method</h3> <p>Twenty-one tumor resection samples from twenty CRC patients from primary site (<i>n</i> = 12) and from intrahepatic metastasis (<i>n</i> = 9), female (<i>n</i> = 6) and male (<i>n</i> = 14) were analyzed. Clinical metadata of donors was associated with molecular properties of each sample. Patients’ cryostored tumor material was blinded before subjecting to PIMS analysis. PIMS analysis was at first performed to separate metastatic and non-metastatic patients. After uncovering the blind, tumors were all challenged by 1 μg of panitumumab in PIMS to identify responder and non-responder with or without metastasis. Tumors from metastatic (<i>n</i> = 3) and non-metastatic (<i>n</i> = 2) patients were thereafter analyzed by NPOT to identify EGFR-related signaling pathway. All group tumors were analyzed using label-free quantitative proteomics.</p> </section> <section> <h3> Results</h3> <p>PIMS identified with 82% accuracy metastatic (<i>n</i> = 9) from non-metastatic (<i>n</i> = 7) tumor. The metastatic tumor had higher resonance volumes (2948–5094) compared to non-metastatic (1076–2759) tumor. NPOT identified EGFR only in metastatic tumor. The metastatic interactome was composed of 34 proteins (EGFR, PTPN1, CTNNB1, CTNND1, YWHAZ, CD44, FN1, ITGB1, GADPH, ENO1, HSPA4, HSPA8, HSP90AA1, HSP90AB1, ANXA2, A1BG, DNTM1, TSR1, RPS27, PPM1G, SMC2, LIG1, NCAPD2, POLD1, PRKDC, YBX1, ANK1, FTL, NCL, ITGB2, SERPINA7, HP, and A2M). The first 10 proteins (underlined) were shared also with non-metastatic tumors. Label-free quantitative proteomics identified 145 differentiated protein, 15 of which were enriched and 130 impoverished specifically in metastatic tumors. Evidence suggests that HSPA4, HSP90AB1, DNTM1, RPS27, FTL, NCL, A2M are implicated in the pathogenesis and progression of colorectal cancer, positioning them as potential prognostic biomarkers for the onset of metastasis.</p> </section> <section> <h3> Conclusion</h3>
{"title":"Molecular Resonance Quantification and Label-Free Interactome Characterization of Total Proteome of Tumor Specimens Decipher Responder and Success Predictors in Colorectal Cancer Patients Treated With Panitumumab","authors":"Angelique Quartier, Ahmed Y. Sanin, Julia Nagelschmitz, Justine Schneider, Wenjie Shi, Thomas Wartmann, Maximilian Dölling, Frederike Stelter, Mihailo Andric, Roland S. Croner, Pierre Eftekhari, Ulf D. Kahlert","doi":"10.1002/cam4.71387","DOIUrl":"10.1002/cam4.71387","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Panitumumab shows limited clinical benefit in colorectal cancer (CRC), and reliable predictive biomarkers to guide patient selection remain lacking. To address this gap, we investigated molecular determinants of therapeutic response using tumor samples from patients with primary and metastatic CRC. By integrating PIMS-based metastatic classification, NPOT interaction profiling and quantitative proteomics, this study aimed to identify response-associated pathways and potential prognostic biomarkers that could support improved stratification for panitumumab therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>Twenty-one tumor resection samples from twenty CRC patients from primary site (<i>n</i> = 12) and from intrahepatic metastasis (<i>n</i> = 9), female (<i>n</i> = 6) and male (<i>n</i> = 14) were analyzed. Clinical metadata of donors was associated with molecular properties of each sample. Patients’ cryostored tumor material was blinded before subjecting to PIMS analysis. PIMS analysis was at first performed to separate metastatic and non-metastatic patients. After uncovering the blind, tumors were all challenged by 1 μg of panitumumab in PIMS to identify responder and non-responder with or without metastasis. Tumors from metastatic (<i>n</i> = 3) and non-metastatic (<i>n</i> = 2) patients were thereafter analyzed by NPOT to identify EGFR-related signaling pathway. All group tumors were analyzed using label-free quantitative proteomics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PIMS identified with 82% accuracy metastatic (<i>n</i> = 9) from non-metastatic (<i>n</i> = 7) tumor. The metastatic tumor had higher resonance volumes (2948–5094) compared to non-metastatic (1076–2759) tumor. NPOT identified EGFR only in metastatic tumor. The metastatic interactome was composed of 34 proteins (EGFR, PTPN1, CTNNB1, CTNND1, YWHAZ, CD44, FN1, ITGB1, GADPH, ENO1, HSPA4, HSPA8, HSP90AA1, HSP90AB1, ANXA2, A1BG, DNTM1, TSR1, RPS27, PPM1G, SMC2, LIG1, NCAPD2, POLD1, PRKDC, YBX1, ANK1, FTL, NCL, ITGB2, SERPINA7, HP, and A2M). The first 10 proteins (underlined) were shared also with non-metastatic tumors. Label-free quantitative proteomics identified 145 differentiated protein, 15 of which were enriched and 130 impoverished specifically in metastatic tumors. Evidence suggests that HSPA4, HSP90AB1, DNTM1, RPS27, FTL, NCL, A2M are implicated in the pathogenesis and progression of colorectal cancer, positioning them as potential prognostic biomarkers for the onset of metastasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 ","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 23","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145627223","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}
Xiaoding Zhou, Ying Liu, Jie Zhu, Jingqiu Li, Yi Wang, Guiyu Huang, Lin Peng, Yongtao Han, Xuefeng Leng, Chenghao Wang, Wenwu He, Lei Wu, Qifeng Wang
Background
The method of lymph node (LN) irradiation for locally advanced esophageal squamous cell carcinoma (LA-ESCC) is still a topic of debate. We investigated the efficacy, toxicity, and rate of out-of-field LNs in irradiation across different target areas in patients with LA-ESCC undergoing neoadjuvant chemoradiotherapy (nCRT).
Methods
We retrospectively reviewed patient records from June 2017 to August 2022 and divided patients into elective nodal irradiation (ENI) and involved-field irradiation (IFI) groups. The differences in hematological and non-hematological toxicities of the out-of-field LNs were analyzed between the two groups. The log-rank test was used to evaluate the Kaplan–Meier curves for overall and progression-free survival.
Results
Among the 306 included patients, 202 (66.0%) received ENI and 104 (34.0%) received IFI. At the 3-year follow-up, the survival rate did not differ significantly between the groups (p > 0.05). Although the occurrence of radiation-induced pneumonia did not differ (p > 0.05), the incidence of radiation-induced esophagitis and the degree of leukopenia differed significantly (p < 0.05). While the average heart irradiation dose or heart V20, V30, and V40 did not differ significantly (p > 0.05), we observed significant differences in the clinical target volume, average lung irradiation dose, and lung V20, V30, and V40 (p < 0.05). Among all patients, 29 cases (9.5%) experienced out-of-field LNs with 26 (93.1%) in abdominal LNs, whereas only 3 cases (6.9%) with out-of-field LNs were in the upper esophagus. There was no statistical significance between out-of-field LNs and LN irradiation methods (p = 0.724).
Conclusions
Under similar prognostic conditions, IFI resulted in mild toxicity compared to ENI. Therefore, for patients with ESCC undergoing nCRT, IFI is the preferred irradiation approach for the lymphatic drainage area.
{"title":"Involved-Field Irradiation Versus Elective Nodal Irradiation in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma Treated With Neoadjuvant Chemoradiotherapy","authors":"Xiaoding Zhou, Ying Liu, Jie Zhu, Jingqiu Li, Yi Wang, Guiyu Huang, Lin Peng, Yongtao Han, Xuefeng Leng, Chenghao Wang, Wenwu He, Lei Wu, Qifeng Wang","doi":"10.1002/cam4.71392","DOIUrl":"10.1002/cam4.71392","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The method of lymph node (LN) irradiation for locally advanced esophageal squamous cell carcinoma (LA-ESCC) is still a topic of debate. We investigated the efficacy, toxicity, and rate of out-of-field LNs in irradiation across different target areas in patients with LA-ESCC undergoing neoadjuvant chemoradiotherapy (nCRT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively reviewed patient records from June 2017 to August 2022 and divided patients into elective nodal irradiation (ENI) and involved-field irradiation (IFI) groups. The differences in hematological and non-hematological toxicities of the out-of-field LNs were analyzed between the two groups. The log-rank test was used to evaluate the Kaplan–Meier curves for overall and progression-free survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 306 included patients, 202 (66.0%) received ENI and 104 (34.0%) received IFI. At the 3-year follow-up, the survival rate did not differ significantly between the groups (<i>p</i> > 0.05). Although the occurrence of radiation-induced pneumonia did not differ (<i>p</i> > 0.05), the incidence of radiation-induced esophagitis and the degree of leukopenia differed significantly (<i>p</i> < 0.05). While the average heart irradiation dose or heart V<sub>20</sub>, V<sub>30</sub>, and V<sub>40</sub> did not differ significantly (<i>p</i> > 0.05), we observed significant differences in the clinical target volume, average lung irradiation dose, and lung V<sub>20</sub>, V<sub>30</sub>, and V<sub>40</sub> (<i>p</i> < 0.05). Among all patients, 29 cases (9.5%) experienced out-of-field LNs with 26 (93.1%) in abdominal LNs, whereas only 3 cases (6.9%) with out-of-field LNs were in the upper esophagus. There was no statistical significance between out-of-field LNs and LN irradiation methods (<i>p</i> = 0.724).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Under similar prognostic conditions, IFI resulted in mild toxicity compared to ENI. Therefore, for patients with ESCC undergoing nCRT, IFI is the preferred irradiation approach for the lymphatic drainage area.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 23","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145627195","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}
Tomas Buchler, Lucie Pehalova Kusova, Alina Pirshtuk, Jan Muzik, Marek Babjuk, Ladislav Dusek
Background
Bladder cancer (BC) is one of the most common cancers and many patients will experience long-term survival. Non-urothelial second primary cancers (SPC) relatively frequently occur in the population of BC survivors.
Methods
Czech National Cancer Registry was the principal data source for this study. The risk of development of non-urothelial SPC after BC was assessed by the standardized incidence ratio (SIR). The standardized mortality ratio (SMR) was utilized to determine the risk of death from SPC following BC.
Results
Of the total of 61,314 patients with BC, a cohort of 12,645 survivors diagnosed with a SPC were analyzed. Compared to the general population, the SIR of neoplasia was significantly increased in BC survivors, with a SIR of 1.75 (95% confidence interval [CI] 1.72–1.78) for all cancers, especially during the first 5 years after BC diagnosis. The SMR was increased in BC survivors (1.25; 95% CI 1.21–1.29) for all cancers. Lung cancer frequently occurred as a SPC and was associated with high mortality in BC survivors. BC survivors also had a higher risk of laryngeal cancer and other cancers known to be strongly associated with smoking, but also of soft tissue tumors, colorectal cancer, chronic lymphocytic leukemia, and thyroid cancer.
Conclusions
The present large registry-based study shows that BC survivors have a significantly higher risk of being diagnosed with another primary cancer compared to the general population, especially during the first 5 years after BC diagnosis. In addition to smoking-related cancers, increased incidence of some cancers not known to be associated with smoking was observed.
背景：膀胱癌（BC）是最常见的癌症之一，许多患者将经历长期生存。非尿路上皮第二原发癌（SPC）相对频繁地发生在BC幸存者人群中。方法：捷克国家癌症登记处是本研究的主要数据来源。通过标准化发病率（SIR）评估BC后发生非尿路上皮性SPC的风险。标准化死亡率（SMR）用于确定BC后SPC的死亡风险。结果：在总共61314例BC患者中，有12645例被诊断为SPC的幸存者进行了分析。与一般人群相比，BC幸存者中肿瘤的SIR显著增加，所有癌症的SIR为1.75(95%可信区间[CI] 1.72-1.78)，特别是在BC诊断后的前5年。所有癌症的BC幸存者的SMR均升高（1.25;95% CI 1.21-1.29）。肺癌经常作为SPC发生，并且与BC幸存者的高死亡率相关。BC幸存者患喉癌和其他已知与吸烟密切相关的癌症的风险也较高，但软组织肿瘤、结直肠癌、慢性淋巴细胞白血病和甲状腺癌的风险也较高。结论：目前基于登记的大型研究表明，与普通人群相比，BC幸存者被诊断为另一种原发性癌症的风险明显更高，特别是在BC诊断后的前5年。除了与吸烟有关的癌症外，还观察到一些与吸烟无关的癌症的发病率增加。
{"title":"Second Primary Cancer After Bladder Cancer: A Comprehensive Analysis of a National Cancer Registry","authors":"Tomas Buchler, Lucie Pehalova Kusova, Alina Pirshtuk, Jan Muzik, Marek Babjuk, Ladislav Dusek","doi":"10.1002/cam4.71427","DOIUrl":"10.1002/cam4.71427","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bladder cancer (BC) is one of the most common cancers and many patients will experience long-term survival. Non-urothelial second primary cancers (SPC) relatively frequently occur in the population of BC survivors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Czech National Cancer Registry was the principal data source for this study. The risk of development of non-urothelial SPC after BC was assessed by the standardized incidence ratio (SIR). The standardized mortality ratio (SMR) was utilized to determine the risk of death from SPC following BC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the total of 61,314 patients with BC, a cohort of 12,645 survivors diagnosed with a SPC were analyzed. Compared to the general population, the SIR of neoplasia was significantly increased in BC survivors, with a SIR of 1.75 (95% confidence interval [CI] 1.72–1.78) for all cancers, especially during the first 5 years after BC diagnosis. The SMR was increased in BC survivors (1.25; 95% CI 1.21–1.29) for all cancers. Lung cancer frequently occurred as a SPC and was associated with high mortality in BC survivors. BC survivors also had a higher risk of laryngeal cancer and other cancers known to be strongly associated with smoking, but also of soft tissue tumors, colorectal cancer, chronic lymphocytic leukemia, and thyroid cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The present large registry-based study shows that BC survivors have a significantly higher risk of being diagnosed with another primary cancer compared to the general population, especially during the first 5 years after BC diagnosis. In addition to smoking-related cancers, increased incidence of some cancers not known to be associated with smoking was observed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 23","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145646824","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}
Several case reports have recounted hiccups as a possible symptom of cancer, but potential associations in large study samples have not been examined.
Methods
This population-based cohort study examined associations between hiccups and subsequent cancer diagnoses. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated.
Results
Of 8466 patients diagnosed with hiccups during the study period (1997–2018), 7531 (89.0%) were men, 4013 (47.4%) were diagnosed in primary healthcare, and 325 (3.8%) were diagnosed with cancer. In men, hiccups were associated with nervous system (SIR 1.94; 95% CI, 1.08–3.20), hematologic (1.52; 1.17–1.93), and gastrointestinal (1.61; 1.36–1.89) cancers, including esophageal (2.63; 1.47–4.43), stomach (2.27; 1.42–3.45), colon (1.61; 1.23–2.08), and liver (1.77; 1.05–2.80) cancers. In women, hiccups were associated with gastrointestinal cancer (2.23; 1.27–3.63). Particularly strong associations were observed within 12 months of follow-up.
Conclusion
These findings may be useful for clinical practice and could provide foundations for detailed clinical studies on hiccups as a potential clinical cancer marker.
背景：一些病例报告称打嗝可能是癌症的一种症状，但在大量研究样本中，潜在的关联尚未得到检验。方法：这项以人群为基础的队列研究考察了打嗝与随后的癌症诊断之间的关系。计算标准化发生率比（SIRs）和95%置信区间（CIs）。结果：在研究期间（1997-2018年）诊断为打嗝的8466例患者中，7531例（89.0%）为男性，4013例（47.4%）为初级保健诊断，325例（3.8%）为癌症诊断。在男性中，打嗝与神经系统癌（SIR 1.94; 95% CI 1.08-3.20）、血液学癌（1.52;1.17-1.93）和胃肠道癌（1.61;1.36-1.89）相关，包括食管癌（2.63;1.47-4.43）、胃癌（2.27;1.42-3.45）、结肠癌（1.61;1.23-2.08）和肝癌（1.77;1.05-2.80）。在女性中，打嗝与胃肠道癌相关（2.23;1.27-3.63）。在12个月的随访中观察到特别强烈的关联。结论：本研究结果具有一定的临床应用价值，为进一步深入研究打嗝作为潜在癌症标志物的临床研究奠定了基础。
{"title":"Associations Between Hiccups and Subsequent Cancer Diagnoses: A Population-Based Cohort Study","authors":"Filip Jansåker, Xinjun Li, Kristina Sundquist","doi":"10.1002/cam4.71441","DOIUrl":"10.1002/cam4.71441","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Several case reports have recounted hiccups as a possible symptom of cancer, but potential associations in large study samples have not been examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This population-based cohort study examined associations between hiccups and subsequent cancer diagnoses. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 8466 patients diagnosed with hiccups during the study period (1997–2018), 7531 (89.0%) were men, 4013 (47.4%) were diagnosed in primary healthcare, and 325 (3.8%) were diagnosed with cancer. In men, hiccups were associated with nervous system (SIR 1.94; 95% CI, 1.08–3.20), hematologic (1.52; 1.17–1.93), and gastrointestinal (1.61; 1.36–1.89) cancers, including esophageal (2.63; 1.47–4.43), stomach (2.27; 1.42–3.45), colon (1.61; 1.23–2.08), and liver (1.77; 1.05–2.80) cancers. In women, hiccups were associated with gastrointestinal cancer (2.23; 1.27–3.63). Particularly strong associations were observed within 12 months of follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings may be useful for clinical practice and could provide foundations for detailed clinical studies on hiccups as a potential clinical cancer marker.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 23","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145627270","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}
Min Zhang, Chanjin Liang, Ting Chen, Xingyuan Shi, Jiqing Hao
Background
Liquid–liquid phase separation (LLPS) has emerged as a critical mechanism underlying oncogenic signaling and transcriptional regulation; however, its involvement in triple-negative breast cancer (TNBC) remains largely unknown. The pleckstrin homology-like domain family B member 2 (PHLDB2) has been implicated in cytoskeletal organization and cell migration, but its role in phase separation–mediated tumor progression has not been explored.
Methods
We conducted an integrative multi-omics analysis combining transcriptomic profiling, bioinformatic modeling, and molecular biology experiments to elucidate the function of PHLDB2 in TNBC. Expression, mutation, and copy number variation of phase separation–related genes were analyzed using TCGA, METABRIC, and GTEx datasets. PHLDB2 knockdown and overexpression models were established in MDA-MB-231 and HCC38 cells to assess cell proliferation, epithelial–mesenchymal transition (EMT), and extracellular matrix (ECM)–related pathways. Immunofluorescence and fluorescence recovery after photobleaching (FRAP) assays were performed to evaluate the phase separation properties of PHLDB2. In vivo, xenograft and pulmonary metastasis models were used to validate the effects of Phldb2 knockdown on TNBC growth and metastasis.
Results
PHLDB2 was significantly upregulated in TNBC and correlated with poor clinical prognosis. Gene ontology and KEGG analyses revealed its enrichment in ECM–receptor interaction and focal adhesion pathways. PHLDB2 knockdown inhibited cell proliferation and migration, suppressed EMT by upregulating E-cadherin and downregulating N-cadherin, vimentin, Snail, and MMP-2. PONDR analysis identified extensive intrinsically disordered regions (IDRs) within PHLDB2, and FRAP assays confirmed its ability to form dynamic, reversible condensates consistent with LLPS. In vivo, Phldb2 depletion markedly reduced tumor growth and pulmonary metastases and prolonged survival in TNBC-bearing mice.
Conclusion
Our findings demonstrate that PHLDB2 promotes TNBC progression by mediating ECM remodeling and EMT activation through phase separation–driven signal organization. These results establish PHLDB2 as a novel phase separation–dependent oncogenic regulator and highlight its potential as a prognostic biomarker and therapeutic target in TNBC.
{"title":"Phase Separation of PHLDB2 Drives EMT and Tumor Progression in Triple-Negative Breast Cancer","authors":"Min Zhang, Chanjin Liang, Ting Chen, Xingyuan Shi, Jiqing Hao","doi":"10.1002/cam4.71308","DOIUrl":"10.1002/cam4.71308","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Liquid–liquid phase separation (LLPS) has emerged as a critical mechanism underlying oncogenic signaling and transcriptional regulation; however, its involvement in triple-negative breast cancer (TNBC) remains largely unknown. The pleckstrin homology-like domain family B member 2 (PHLDB2) has been implicated in cytoskeletal organization and cell migration, but its role in phase separation–mediated tumor progression has not been explored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted an integrative multi-omics analysis combining transcriptomic profiling, bioinformatic modeling, and molecular biology experiments to elucidate the function of PHLDB2 in TNBC. Expression, mutation, and copy number variation of phase separation–related genes were analyzed using TCGA, METABRIC, and GTEx datasets. PHLDB2 knockdown and overexpression models were established in MDA-MB-231 and HCC38 cells to assess cell proliferation, epithelial–mesenchymal transition (EMT), and extracellular matrix (ECM)–related pathways. Immunofluorescence and fluorescence recovery after photobleaching (FRAP) assays were performed to evaluate the phase separation properties of PHLDB2. In vivo, xenograft and pulmonary metastasis models were used to validate the effects of Phldb2 knockdown on TNBC growth and metastasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PHLDB2 was significantly upregulated in TNBC and correlated with poor clinical prognosis. Gene ontology and KEGG analyses revealed its enrichment in ECM–receptor interaction and focal adhesion pathways. PHLDB2 knockdown inhibited cell proliferation and migration, suppressed EMT by upregulating E-cadherin and downregulating N-cadherin, vimentin, Snail, and MMP-2. PONDR analysis identified extensive intrinsically disordered regions (IDRs) within PHLDB2, and FRAP assays confirmed its ability to form dynamic, reversible condensates consistent with LLPS. In vivo, Phldb2 depletion markedly reduced tumor growth and pulmonary metastases and prolonged survival in TNBC-bearing mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings demonstrate that PHLDB2 promotes TNBC progression by mediating ECM remodeling and EMT activation through phase separation–driven signal organization. These results establish PHLDB2 as a novel phase separation–dependent oncogenic regulator and highlight its potential as a prognostic biomarker and therapeutic target in TNBC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 23","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145627261","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}
Muhammad Ali Khan, Syed Arsalan Ahmed Naqvi, John K. Camoriano, Cecilia Y. Arana Yi, Jennifer T. Andres, Joshua L. Blocher, Heidi E. Kosiorek, Irbaz Bin Riaz, Jeanne M. Palmer
Background
Symptom management in myeloproliferative neoplasms (MPN) remains challenging despite advancements in disease-directed therapies. This study assessed the impact of demographic, clinical, laboratory and treatment-related variables on total symptom scores (TSS) and individual symptom scores in patients with polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF).
Methods
A cohort of 553 patients (PV: 200; ET: 190; MF: 163) was identified through a retrospective chart review. Symptom scores, demographic information and clinical variables were captured at the time of the first TSS assessment. Laboratory results within 1 month and treatment information within 90 days prior to the symptom assessment were captured. Univariable linear regression, followed by multivariable regression analyses using a robust variance estimator were performed, with a p value < 0.05 indicating a significant association.
Results
MF patients experienced the highest symptom burden and fatigue was the most reported symptom across all MPN subtypes. In PV, depression (β: 10.53; p = 0.001) was associated with a higher TSS whereas older age (−0.17; 0.01) and higher hemoglobin (−1.24; 0.003) were associated with a lower TSS. In ET, depression (β: 14.19; p < 0.001) was associated with a higher TSS, whereas in MF, depression (12.28; < 0.001) and higher WBC count (0.22; 0.02) were associated with a higher TSS. Depression and non-White race in PV, depression in ET, and depression, low hemoglobin, and higher WBC count in MF were associated with multiple symptoms.
Conclusions
Integrating depression screening and management and optimizing hematologic parameters alongside disease-directed therapy is crucial to improving patient outcomes.
背景：尽管疾病导向疗法取得进展，骨髓增生性肿瘤（MPN）的症状管理仍然具有挑战性。本研究评估了真性红细胞增多症（PV）、原发性血小板增多症（ET）和骨髓纤维化（MF）患者的人口学、临床、实验室和治疗相关变量对总症状评分（TSS）和个体症状评分的影响。方法回顾性分析553例患者（PV: 200, ET: 190, MF: 163）。在第一次TSS评估时捕获症状评分、人口统计信息和临床变量。收集症状评估前1个月内的实验室结果和90天内的治疗信息。单变量线性回归，然后使用稳健方差估计器进行多变量回归分析，p值<； 0.05表示显著相关。结果MF患者的症状负担最重，疲劳是所有MPN亚型中报告最多的症状。在PV中，抑郁（β: 10.53; p = 0.001）与较高的TSS相关，而年龄较大（- 0.17;0.01）和较高的血红蛋白（- 1.24;0.003）与较低的TSS相关。在ET中，抑郁（β: 14.19; p < 0.001）与较高的TSS相关，而在MF中，抑郁（12.28;< 0.001）和较高的WBC计数（0.22;0.02）与较高的TSS相关。PV患者抑郁和非白种人，ET患者抑郁，MF患者抑郁、低血红蛋白和高白细胞计数与多种症状相关。结论整合抑郁症筛查和管理，优化血液学参数以及疾病定向治疗对改善患者预后至关重要。
{"title":"Predictors of Symptom Scores in Myeloproliferative Neoplasms: A Real-World Retrospective Cohort Study","authors":"Muhammad Ali Khan, Syed Arsalan Ahmed Naqvi, John K. Camoriano, Cecilia Y. Arana Yi, Jennifer T. Andres, Joshua L. Blocher, Heidi E. Kosiorek, Irbaz Bin Riaz, Jeanne M. Palmer","doi":"10.1002/cam4.71333","DOIUrl":"https://doi.org/10.1002/cam4.71333","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Symptom management in myeloproliferative neoplasms (MPN) remains challenging despite advancements in disease-directed therapies. This study assessed the impact of demographic, clinical, laboratory and treatment-related variables on total symptom scores (TSS) and individual symptom scores in patients with polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cohort of 553 patients (PV: 200; ET: 190; MF: 163) was identified through a retrospective chart review. Symptom scores, demographic information and clinical variables were captured at the time of the first TSS assessment. Laboratory results within 1 month and treatment information within 90 days prior to the symptom assessment were captured. Univariable linear regression, followed by multivariable regression analyses using a robust variance estimator were performed, with a <i>p</i> value < 0.05 indicating a significant association.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MF patients experienced the highest symptom burden and fatigue was the most reported symptom across all MPN subtypes. In PV, depression (<i>β</i>: 10.53; <i>p</i> = 0.001) was associated with a higher TSS whereas older age (−0.17; 0.01) and higher hemoglobin (−1.24; 0.003) were associated with a lower TSS. In ET, depression (<i>β</i>: 14.19; <i>p</i> < 0.001) was associated with a higher TSS, whereas in MF, depression (12.28; < 0.001) and higher WBC count (0.22; 0.02) were associated with a higher TSS. Depression and non-White race in PV, depression in ET, and depression, low hemoglobin, and higher WBC count in MF were associated with multiple symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Integrating depression screening and management and optimizing hematologic parameters alongside disease-directed therapy is crucial to improving patient outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 23","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71333","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626629","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}
Frantisek Zitricky, Kristina Sundquist, Jan Sundquist, Asta Försti, Akseli Hemminki, Kari Hemminki
Background
Familial clustering of initial primary lung cancer (IPLC) may be related to shared smoking habits, other environmental exposures and hereditary factors, but whether familial risk also influences the risk of second primary LC (SPLC) is not well known. We aimed to carry out a family study between first-degree relatives on SPLCs in Sweden.
Methods
Population data on Swedish family relationships and the diagnosed cancers were obtained from the national registers from 1961 to 2021. IPLC was diagnosed in 54,429 patients of whom 534 were diagnosed with SPLC. Familial risk was assessed through the standardized incidence ratio (SIR with 95% confidence interval) adjusted for several potential confounders, including sex, age, calendar period, educational level and geographic region. Familial risks were analyzed by type of proband, histology and sex. In addition, we estimated the effect of family history on the cumulative proportion of patients developing SPLC by sex and histology.
Results
The estimated SIR for SPLC was 3.98 in patients without family history and 5.24 among those with a history of lung cancer in first-degree relatives. The SIR values depended on the histology of IPLC and of SPLC, with the highest SIRs for concordant histologies. For the adenocarcinoma-adenocarcinoma sequence, SIR estimates were 5.60 and 7.51 for non-familial and familial patients, respectively. The familial risks were further modulated by sex and type of affected relative, with the highest SIR for females with affected mothers (9.14).
Conclusions
The results showed a positive association of family history of LC with risk of SPLC on top of high risk for SPLC in non-familial patients. The risks differed by sex, histology and type of affected relative. The data on family history of LC should alert about surveillance for SPLC and may be used in future risk stratification when eligibility for population screening is considered.
{"title":"Second Primary Lung Cancer Associated With Family History of Lung Cancer","authors":"Frantisek Zitricky, Kristina Sundquist, Jan Sundquist, Asta Försti, Akseli Hemminki, Kari Hemminki","doi":"10.1002/cam4.71431","DOIUrl":"https://doi.org/10.1002/cam4.71431","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Familial clustering of initial primary lung cancer (IPLC) may be related to shared smoking habits, other environmental exposures and hereditary factors, but whether familial risk also influences the risk of second primary LC (SPLC) is not well known. We aimed to carry out a family study between first-degree relatives on SPLCs in Sweden.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Population data on Swedish family relationships and the diagnosed cancers were obtained from the national registers from 1961 to 2021. IPLC was diagnosed in 54,429 patients of whom 534 were diagnosed with SPLC. Familial risk was assessed through the standardized incidence ratio (SIR with 95% confidence interval) adjusted for several potential confounders, including sex, age, calendar period, educational level and geographic region. Familial risks were analyzed by type of proband, histology and sex. In addition, we estimated the effect of family history on the cumulative proportion of patients developing SPLC by sex and histology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The estimated SIR for SPLC was 3.98 in patients without family history and 5.24 among those with a history of lung cancer in first-degree relatives. The SIR values depended on the histology of IPLC and of SPLC, with the highest SIRs for concordant histologies. For the adenocarcinoma-adenocarcinoma sequence, SIR estimates were 5.60 and 7.51 for non-familial and familial patients, respectively. The familial risks were further modulated by sex and type of affected relative, with the highest SIR for females with affected mothers (9.14).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The results showed a positive association of family history of LC with risk of SPLC on top of high risk for SPLC in non-familial patients. The risks differed by sex, histology and type of affected relative. The data on family history of LC should alert about surveillance for SPLC and may be used in future risk stratification when eligibility for population screening is considered.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 23","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71431","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626628","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}
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