The effects of cofactors on the impact of body mass index (BMI) change on breast and endometrial cancer are rarely investigated. This cohort study included cancer-free women who underwent national health examinations in 2010-2014 (Cohort 1) and 2009-2013 (Cohort 2), with follow-up through 2021 and 2017, respectively. BMI at baseline and follow-up was combined and categorized into 25 BMI change patterns. Cohort 1 (2.24 million) had 30,323 breast and 5465 uterine corpus cancers, while Cohort 2 (1.46 million) had 8580 breast and 1170 uterine corpus cancers. In Cohort 1, persistent low BMI was associated with a reduced risk of both cancers, particularly in postmenopausal women and never-smokers. However, persistent overweight, obesity I/II, and BMI fluctuation (loss or gain) were linked to an increased risk of both cancers, particularly in postmenopausal women and ever-smokers. Among premenopausal women, substantial BMI loss was associated with increased breast cancer risk. In postmenopausal women, a transition from overweight to underweight (adjusted hazard ratio [aHR]: 4.63, 95% confidence interval [CI]: 1.15-18.59) and from overweight to obesity class II (aHR: 4.06, 95% CI: 1.01-16.30) significantly increased uterine cancer risk. Among smokers, most BMI changes did not show significant association, except for persistent obesity I (aHR: 1.57, 95% CI: 1.01-2.43) and progression from obesity class I to II (aHR: 4.03, 95% CI: 1.97-8.26). Cohort 2 findings were largely consistent with those from Cohort 1. In conclusion, persistent high BMI and further BMI gain were associated with increased risk of both cancers, particularly in postmenopausal women and never-smokers.
{"title":"The effect of body mass index change on breast and uterine cancer risk in middle- and older-aged adults.","authors":"Su Youn Nam, Junwoo Jo","doi":"10.1002/ijc.70325","DOIUrl":"https://doi.org/10.1002/ijc.70325","url":null,"abstract":"<p><p>The effects of cofactors on the impact of body mass index (BMI) change on breast and endometrial cancer are rarely investigated. This cohort study included cancer-free women who underwent national health examinations in 2010-2014 (Cohort 1) and 2009-2013 (Cohort 2), with follow-up through 2021 and 2017, respectively. BMI at baseline and follow-up was combined and categorized into 25 BMI change patterns. Cohort 1 (2.24 million) had 30,323 breast and 5465 uterine corpus cancers, while Cohort 2 (1.46 million) had 8580 breast and 1170 uterine corpus cancers. In Cohort 1, persistent low BMI was associated with a reduced risk of both cancers, particularly in postmenopausal women and never-smokers. However, persistent overweight, obesity I/II, and BMI fluctuation (loss or gain) were linked to an increased risk of both cancers, particularly in postmenopausal women and ever-smokers. Among premenopausal women, substantial BMI loss was associated with increased breast cancer risk. In postmenopausal women, a transition from overweight to underweight (adjusted hazard ratio [aHR]: 4.63, 95% confidence interval [CI]: 1.15-18.59) and from overweight to obesity class II (aHR: 4.06, 95% CI: 1.01-16.30) significantly increased uterine cancer risk. Among smokers, most BMI changes did not show significant association, except for persistent obesity I (aHR: 1.57, 95% CI: 1.01-2.43) and progression from obesity class I to II (aHR: 4.03, 95% CI: 1.97-8.26). Cohort 2 findings were largely consistent with those from Cohort 1. In conclusion, persistent high BMI and further BMI gain were associated with increased risk of both cancers, particularly in postmenopausal women and never-smokers.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145891747","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}
Yi-Long Wu, Li Zhang, Yun Fan, JianYing Zhou, Li Zhang, Qing Zhou, Wei Li, ChengPing Hu, GongYan Chen, Xin Zhang, CaiCun Zhou, Carmen González Arenas, Zhenghong Chen, Wen Cheng Yu, Tony S K Mok
In the phase 3 KEYNOTE-042 China study of participants enrolled in China in the global KEYNOTE-042 (NCT02220894) and China extension (NCT03850444) studies, pembrolizumab improved overall survival (OS) versus chemotherapy in locally advanced or metastatic non-small-cell lung cancer (NSCLC) with programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥50% (hazard ratio [HR], 0.63; 95% CI, 0.43-0.94), ≥20% (0.66; 0.47-0.92), and ≥1% (0.67; 0.50-0.89). We present outcomes from this study after 5 years of follow-up. Chinese participants with previously untreated locally advanced or metastatic NSCLC with PD-L1 TPS ≥1% without EGFR or ALK alterations were eligible. Participants were randomized 1:1 to pembrolizumab 200 mg every 3 weeks for up to 35 cycles or carboplatin plus paclitaxel or pemetrexed with optional pemetrexed maintenance (nonsquamous only). Primary endpoints were OS in the PD-L1 TPS ≥50%, ≥20%, and ≥1% subgroups. Median follow-up was 63.7 (range, 56.3-72.6) months among 262 participants (pembrolizumab, n = 128; chemotherapy, n = 134) included in this study. Pembrolizumab prolonged OS versus chemotherapy in participants with PD-L1 TPS ≥50% (HR, 0.65; 95% CI, 0.45-0.93), ≥20% (0.67; 0.49-0.91), and ≥1% (0.66; 0.51-0.87). Grade 3 to 5 treatment-related AEs occurred in 19.5% and 68.8% of participants in the pembrolizumab and chemotherapy groups, respectively. In conclusion, after 5 years of follow-up, pembrolizumab continued to demonstrate improved OS versus chemotherapy with manageable safety in Chinese participants with previously untreated locally advanced or metastatic NSCLC that expressed PD-L1. These data further support pembrolizumab monotherapy as a standard of care for these patients.
{"title":"Five-year outcomes of pembrolizumab versus chemotherapy in Chinese patients with non-small-cell lung cancer and programmed cell death ligand 1 tumor proportion score ≥1%: KEYNOTE-042 China study.","authors":"Yi-Long Wu, Li Zhang, Yun Fan, JianYing Zhou, Li Zhang, Qing Zhou, Wei Li, ChengPing Hu, GongYan Chen, Xin Zhang, CaiCun Zhou, Carmen González Arenas, Zhenghong Chen, Wen Cheng Yu, Tony S K Mok","doi":"10.1002/ijc.70265","DOIUrl":"https://doi.org/10.1002/ijc.70265","url":null,"abstract":"<p><p>In the phase 3 KEYNOTE-042 China study of participants enrolled in China in the global KEYNOTE-042 (NCT02220894) and China extension (NCT03850444) studies, pembrolizumab improved overall survival (OS) versus chemotherapy in locally advanced or metastatic non-small-cell lung cancer (NSCLC) with programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥50% (hazard ratio [HR], 0.63; 95% CI, 0.43-0.94), ≥20% (0.66; 0.47-0.92), and ≥1% (0.67; 0.50-0.89). We present outcomes from this study after 5 years of follow-up. Chinese participants with previously untreated locally advanced or metastatic NSCLC with PD-L1 TPS ≥1% without EGFR or ALK alterations were eligible. Participants were randomized 1:1 to pembrolizumab 200 mg every 3 weeks for up to 35 cycles or carboplatin plus paclitaxel or pemetrexed with optional pemetrexed maintenance (nonsquamous only). Primary endpoints were OS in the PD-L1 TPS ≥50%, ≥20%, and ≥1% subgroups. Median follow-up was 63.7 (range, 56.3-72.6) months among 262 participants (pembrolizumab, n = 128; chemotherapy, n = 134) included in this study. Pembrolizumab prolonged OS versus chemotherapy in participants with PD-L1 TPS ≥50% (HR, 0.65; 95% CI, 0.45-0.93), ≥20% (0.67; 0.49-0.91), and ≥1% (0.66; 0.51-0.87). Grade 3 to 5 treatment-related AEs occurred in 19.5% and 68.8% of participants in the pembrolizumab and chemotherapy groups, respectively. In conclusion, after 5 years of follow-up, pembrolizumab continued to demonstrate improved OS versus chemotherapy with manageable safety in Chinese participants with previously untreated locally advanced or metastatic NSCLC that expressed PD-L1. These data further support pembrolizumab monotherapy as a standard of care for these patients.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145861403","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}
Adino T Tsegaye, Sizeka A Mashele, Jaimie Z Shing, Judith Mwansa-Kambafwile, Aimée R Kreimer, Carole Metekoua, Meredith S Shiels, Mazvita Muchengeti
Evaluating trends in HPV-related cancer rates by race is essential for identifying high-risk populations and improving prevention efforts. Using 2011-2022 South African National Cancer Registry data, we analyzed age-standardized incidence rates by race and sex across three periods (2011-2014, 2015-2018, 2019-2022) using linear regression. Significant increases were observed for oropharyngeal squamous cell carcinoma (SCC) among White females (p < .01), vulvar SCC among Asian (p < .01) and Black (p = .02) females, and anal SCC among Colored females and Black males (p < .01). Cervical carcinoma rates remained stable for most racial groups, except for the annual trends showing a 1.9% increase per year (95% CI = 1.0, 2.7) among White females. These findings suggest rising incidence rates for some HPV-related cancers across racial groups in South Africa. Further research is needed to explore the constellation of risk factors contributing to these trends and to guide targeted interventions.
{"title":"Race-specific temporal trends of HPV-related cancers in South Africa: An analysis of the South African National Cancer Registry, 2011-2022.","authors":"Adino T Tsegaye, Sizeka A Mashele, Jaimie Z Shing, Judith Mwansa-Kambafwile, Aimée R Kreimer, Carole Metekoua, Meredith S Shiels, Mazvita Muchengeti","doi":"10.1002/ijc.70323","DOIUrl":"https://doi.org/10.1002/ijc.70323","url":null,"abstract":"<p><p>Evaluating trends in HPV-related cancer rates by race is essential for identifying high-risk populations and improving prevention efforts. Using 2011-2022 South African National Cancer Registry data, we analyzed age-standardized incidence rates by race and sex across three periods (2011-2014, 2015-2018, 2019-2022) using linear regression. Significant increases were observed for oropharyngeal squamous cell carcinoma (SCC) among White females (p < .01), vulvar SCC among Asian (p < .01) and Black (p = .02) females, and anal SCC among Colored females and Black males (p < .01). Cervical carcinoma rates remained stable for most racial groups, except for the annual trends showing a 1.9% increase per year (95% CI = 1.0, 2.7) among White females. These findings suggest rising incidence rates for some HPV-related cancers across racial groups in South Africa. Further research is needed to explore the constellation of risk factors contributing to these trends and to guide targeted interventions.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145861454","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}
Esraa Ali, Wenjing Ye, Sergii Pavlov, Lenka Červenková, Filip Ambrozkiewicz, Ondřej Vyčítal, Petr Hošek, Ondřej Daum, Václav Liška, Kari Hemminki, Andriy Trailin
Analyzing T-cell subsets in and between primary colorectal cancer (pCRC) and adjacent non-tumor mucosa (NM) may reveal distinct prognostic value in stage IV versus stages I-III patients. Specimens of pCRC and NM were collected retrospectively from stage IV patients (n = 55) with synchronous liver metastases (LM), and stages I-III patients (n = 44) who developed metachronous LM. CD3+, CD8+, CD45RO+, CD4+, and Foxp3+ T-cells were quantified in NM and the tumor center (TC) of pCRC using immunohistochemistry. T-cell densities in NM and TC and their ratios (TC/NM) were tested as prognostic variables for overall survival (OS), along with Foxp3+/CD8+, Foxp3+/CD4+ and CD4+/CD8+ ratios. In stages I-III, associations with the time to occurrence of LM were also evaluated. In both groups, NM exhibited greater densities of CD3+, CD8+, CD45RO+, and CD4+ cells compared to TC, whereas Foxp3+ cells were more abundant in the TC. In stage IV, high densities of Foxp3+ cells, high Foxp3+/CD4+ and Foxp3+/CD8+ ratios in the NM, and high CD4+ cell densities in the TC were associated with longer OS. Stages I-III patients with a high CD4+/CD8+ ratio in the NM had longer OS, whereas a high Foxp3+/CD8+ ratio in the TC was associated with a shorter time to LM. We revealed a significant difference in the T-cell landscape between pCRC and adjacent NM with Foxp3+ cells predominating in the TC and other subsets in the NM. Assessing T-cells and their ratios in both regions may improve prediction of survival in CRC patients and the time to LM in stages I-III.
{"title":"Distribution and prognostic value of T-cells in primary colorectal cancer and adjacent non-tumor mucosa in stage IV versus stage I-III patients.","authors":"Esraa Ali, Wenjing Ye, Sergii Pavlov, Lenka Červenková, Filip Ambrozkiewicz, Ondřej Vyčítal, Petr Hošek, Ondřej Daum, Václav Liška, Kari Hemminki, Andriy Trailin","doi":"10.1002/ijc.70319","DOIUrl":"https://doi.org/10.1002/ijc.70319","url":null,"abstract":"<p><p>Analyzing T-cell subsets in and between primary colorectal cancer (pCRC) and adjacent non-tumor mucosa (NM) may reveal distinct prognostic value in stage IV versus stages I-III patients. Specimens of pCRC and NM were collected retrospectively from stage IV patients (n = 55) with synchronous liver metastases (LM), and stages I-III patients (n = 44) who developed metachronous LM. CD3<sup>+</sup>, CD8<sup>+</sup>, CD45RO<sup>+</sup>, CD4<sup>+</sup>, and Foxp3<sup>+</sup> T-cells were quantified in NM and the tumor center (TC) of pCRC using immunohistochemistry. T-cell densities in NM and TC and their ratios (TC/NM) were tested as prognostic variables for overall survival (OS), along with Foxp3<sup>+</sup>/CD8<sup>+</sup>, Foxp3<sup>+</sup>/CD4<sup>+</sup> and CD4<sup>+</sup>/CD8<sup>+</sup> ratios. In stages I-III, associations with the time to occurrence of LM were also evaluated. In both groups, NM exhibited greater densities of CD3<sup>+</sup>, CD8<sup>+</sup>, CD45RO<sup>+</sup>, and CD4<sup>+</sup> cells compared to TC, whereas Foxp3<sup>+</sup> cells were more abundant in the TC. In stage IV, high densities of Foxp3<sup>+</sup> cells, high Foxp3<sup>+</sup>/CD4<sup>+</sup> and Foxp3<sup>+</sup>/CD8<sup>+</sup> ratios in the NM, and high CD4<sup>+</sup> cell densities in the TC were associated with longer OS. Stages I-III patients with a high CD4<sup>+</sup>/CD8<sup>+</sup> ratio in the NM had longer OS, whereas a high Foxp3<sup>+</sup>/CD8<sup>+</sup> ratio in the TC was associated with a shorter time to LM. We revealed a significant difference in the T-cell landscape between pCRC and adjacent NM with Foxp3<sup>+</sup> cells predominating in the TC and other subsets in the NM. Assessing T-cells and their ratios in both regions may improve prediction of survival in CRC patients and the time to LM in stages I-III.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145852933","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}
Persistent infection with human papillomavirus (HPV) is associated with an increased risk of head and neck cancers (HNC), particularly oropharyngeal cancer. This longitudinal cohort study investigated the prevalence and dynamics of oral HPV infection among healthy adults in South India. A total of 5325 participants were enrolled, and demographic, behavioral, and oral gargle samples were collected. HPV deoxyribonucleic acid (DNA) was detected using nested PCR (PGMY/GP) and genotyped by Sanger sequencing. HPV16 messenger ribonucleic acid (mRNA) expression was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and validated using droplet digital polymerase chain reaction (ddPCR). Logistic regression analyses were performed to estimate odds ratios. At baseline, 5011 samples were analyzed; 274 (5.5%) were HPV-positive and 4737 were negative. Among 3792 initially HPV-negative participants followed up, 126 (3.3%) acquired new infections (median 8 months; range, 6-15 months). Of 274 baseline HPV-positive individuals, 241 were followed up: 24 (10%) showed persistence, while 217 (90%) cleared infection after a median of 9 months (range, 6-20 months). Sanger sequencing of 471 samples from prevalent and incident infections yielded 290 (61.6%) high-quality sequences; 284 (98%) were HPV16, with isolated detections of HPV18, HPV66, HPV70, and HPV89. Ten novel variants were identified-nine HPV16 and one HPV89-while remaining sequences aligned with established Indian cervical HPV lineages. None of the 176 HPV16 DNA-positive samples analyzed expressed mRNA by RT-PCR, confirmed in 136 samples using ddPCR. Oral HPV infection among healthy individuals in India appears predominantly transient. Long-term monitoring may elucidate the oncogenic potential of oral HPV in this population.
{"title":"Prevalence, incidence, and dynamics of oral human papillomavirus infection among healthy individuals-A molecular epidemiology field study from India.","authors":"Nandimandalam Venkata Vani, Rajendran Madhanagopal, Malliga J Subramanian, Shirley Sundersingh, Antony Xavier Helen, Balaiah Meenakumari, Deva Magendhra Rao, Trivadi Sundaram Ganesan, Rajaraman Swaminathan","doi":"10.1002/ijc.70298","DOIUrl":"https://doi.org/10.1002/ijc.70298","url":null,"abstract":"<p><p>Persistent infection with human papillomavirus (HPV) is associated with an increased risk of head and neck cancers (HNC), particularly oropharyngeal cancer. This longitudinal cohort study investigated the prevalence and dynamics of oral HPV infection among healthy adults in South India. A total of 5325 participants were enrolled, and demographic, behavioral, and oral gargle samples were collected. HPV deoxyribonucleic acid (DNA) was detected using nested PCR (PGMY/GP) and genotyped by Sanger sequencing. HPV16 messenger ribonucleic acid (mRNA) expression was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and validated using droplet digital polymerase chain reaction (ddPCR). Logistic regression analyses were performed to estimate odds ratios. At baseline, 5011 samples were analyzed; 274 (5.5%) were HPV-positive and 4737 were negative. Among 3792 initially HPV-negative participants followed up, 126 (3.3%) acquired new infections (median 8 months; range, 6-15 months). Of 274 baseline HPV-positive individuals, 241 were followed up: 24 (10%) showed persistence, while 217 (90%) cleared infection after a median of 9 months (range, 6-20 months). Sanger sequencing of 471 samples from prevalent and incident infections yielded 290 (61.6%) high-quality sequences; 284 (98%) were HPV16, with isolated detections of HPV18, HPV66, HPV70, and HPV89. Ten novel variants were identified-nine HPV16 and one HPV89-while remaining sequences aligned with established Indian cervical HPV lineages. None of the 176 HPV16 DNA-positive samples analyzed expressed mRNA by RT-PCR, confirmed in 136 samples using ddPCR. Oral HPV infection among healthy individuals in India appears predominantly transient. Long-term monitoring may elucidate the oncogenic potential of oral HPV in this population.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145852865","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}
Tamara König, Nikolaus Christian Simon Mezger, Ole Stoeter, Phoebe Mary Amulen, Margaret Borok, Gladys C Chesumbai, Moudiongui MBoungou Dimitry, Ima-Obong Ekanem, Adugna Fekadu, Bakarou Kamaté, William Muller, Alex Alain Kabena Nzambikolo, Abidemi Omonisi, Furaha Serventi, Markus Wallwiener, Biying Liu, Donald Maxwell Parkin, Pablo Sandro Carvalho Santos, Eva Johanna Kantelhardt, Eric Sven Kroeber
Chemotherapy is an essential component of cancer treatment, as outlined in the National Comprehensive Cancer Network (NCCN) guidelines for Sub-Saharan Africa (SSA). Lack of access to treatment is a key driver of impaired survival rates. This study assessed patient-perceived barriers to chemotherapy in SSA according to the five dimensions of access to care: availability, accessibility, accommodation, affordability, and acceptability. Telephone interviews were conducted with 553 randomly selected cancer patients (or caretakers), registered between 2018 and 2019 in 11 urban population-based cancer registries across nine countries in SSA. Malignancy types included breast, cervical, prostate, and colorectal cancer; non-Hodgkin lymphoma; and Kaposi sarcoma. Patients rated barriers using a 3-point Likert scale. Barriers to chemotherapy and their associations with patient characteristics were analysed using multivariate ordinal regression analysis. Major barriers included accessibility (cost of transport), affordability (cost of treatment, being absent from home), and acceptability (lack of knowledge/awareness and fear of treatment). Results varied between countries: affordability was especially severe in the Republic of Congo, while in Gabon, fear of treatment prevailed. Knowledge and awareness were particularly concerning in Ethiopia and Zimbabwe. A combined educational level and self-reported wealth variable, and national human development index (HDI) were consistently associated with reported barriers. Overall, 58.6% of participants received chemotherapy, while 13.2% were recommended chemotherapy but did not receive it. A higher HDI correlated with an increased probability of receiving treatment. A complex set of barriers influenced patients' non-receipt of treatment. Regionally adapted strategies, including psychosocial support, financial assistance for vulnerable groups, and education, are essential to improve treatment uptake in SSA.
{"title":"Patient- and caregiver-reported barriers to chemotherapy in nine sub-Saharan African countries: A cross-sectional survey among population-based registries.","authors":"Tamara König, Nikolaus Christian Simon Mezger, Ole Stoeter, Phoebe Mary Amulen, Margaret Borok, Gladys C Chesumbai, Moudiongui MBoungou Dimitry, Ima-Obong Ekanem, Adugna Fekadu, Bakarou Kamaté, William Muller, Alex Alain Kabena Nzambikolo, Abidemi Omonisi, Furaha Serventi, Markus Wallwiener, Biying Liu, Donald Maxwell Parkin, Pablo Sandro Carvalho Santos, Eva Johanna Kantelhardt, Eric Sven Kroeber","doi":"10.1002/ijc.70309","DOIUrl":"https://doi.org/10.1002/ijc.70309","url":null,"abstract":"<p><p>Chemotherapy is an essential component of cancer treatment, as outlined in the National Comprehensive Cancer Network (NCCN) guidelines for Sub-Saharan Africa (SSA). Lack of access to treatment is a key driver of impaired survival rates. This study assessed patient-perceived barriers to chemotherapy in SSA according to the five dimensions of access to care: availability, accessibility, accommodation, affordability, and acceptability. Telephone interviews were conducted with 553 randomly selected cancer patients (or caretakers), registered between 2018 and 2019 in 11 urban population-based cancer registries across nine countries in SSA. Malignancy types included breast, cervical, prostate, and colorectal cancer; non-Hodgkin lymphoma; and Kaposi sarcoma. Patients rated barriers using a 3-point Likert scale. Barriers to chemotherapy and their associations with patient characteristics were analysed using multivariate ordinal regression analysis. Major barriers included accessibility (cost of transport), affordability (cost of treatment, being absent from home), and acceptability (lack of knowledge/awareness and fear of treatment). Results varied between countries: affordability was especially severe in the Republic of Congo, while in Gabon, fear of treatment prevailed. Knowledge and awareness were particularly concerning in Ethiopia and Zimbabwe. A combined educational level and self-reported wealth variable, and national human development index (HDI) were consistently associated with reported barriers. Overall, 58.6% of participants received chemotherapy, while 13.2% were recommended chemotherapy but did not receive it. A higher HDI correlated with an increased probability of receiving treatment. A complex set of barriers influenced patients' non-receipt of treatment. Regionally adapted strategies, including psychosocial support, financial assistance for vulnerable groups, and education, are essential to improve treatment uptake in SSA.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145852928","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}
Khadija Sana Hafeez, Carla Debernardi, Alessandra Allione, Elton Jalis Herman, Simonetta Guarrera, Daniela Ferrante, Anna Aspesi, Marika Sculco, Marta La Vecchia, Carlotta Sacerdote, Federica Grosso, Christina M Lill, Giovanna Masala, Marcela Guevara, Matthias B Schulze, Salvatore Panico, Yaszan Asgari, Seehyun Park, Giovanna Tagliabue, Anne Tjønneland, Antonio Agudo, Elisabete Weiderpass, Corrado Magnani, Irma Dianzani, Paolo Vineis, Elisabetta Casalone, Giuseppe Matullo
Pleural mesothelioma (PM) is a lethal cancer primarily caused by asbestos exposure. Not all exposed individuals develop PM, suggesting the involvement of additional factors. This underscores the need for robust predictive models integrating biomarkers from multi-omic domains to improve risk stratification and early detection. We developed and evaluated polygenic risk scores (PRS) and methylation risk scores (MRS) using a retrospective case-control study (749 participants: 387 PM cases, 362 controls) and a nested case-control European Prospective Investigation into Cancer and Nutrition (EPIC)-Meso study (268 participants: 134 preclinical PM cases, 134 matched controls) within the EPIC cohort. Genome-wide association analyses in the retrospective case-control study identified PM-associated variants. The PRS (1123 SNPs with p < 0.001) in the retrospective training subset stratified disease risk in the test set (ORs 3.46-9.54 across top percentiles) and improved model discrimination (AUC = 0.75 vs. 0.71 in baseline model, p = 0.04). In EPIC-Meso, PRS performance was limited (AUC = 0.52). External validation in the UK-Biobank (UKBB) confirmed a modest but consistent association with PM-risk. A Meta-PRS derived from the UKBB-FinnGen meta-analysis replicated this trend in the full retrospective dataset, showing higher OR across top percentiles (2.5-12.3) and improved discrimination (AUC 0.74 vs. 0.72, p = 0.016). MRS, with 68 differentially methylated CpGs (effect-size >|0.10|, FDR p < 0.05) in the retrospective training set, increased the AUC from 0.66 to 0.85 (p < 0.001) in the test set and from 0.51 to 0.62 in EPIC-Meso. PRS was most predictive in low-exposure groups, while MRS remained robust across exposure levels. Combined PRS-MRS models improved discrimination. Integrating multi-omic biomarkers can enhance PM-risk stratification and support earlier, targeted interventions in high-risk asbestos-exposed groups.
胸膜间皮瘤(PM)是一种主要由石棉暴露引起的致命癌症。并非所有暴露的个体都会发展为PM,这表明还涉及其他因素。这强调了整合来自多组学域的生物标志物的强大预测模型的需求,以改善风险分层和早期检测。我们通过一项回顾性病例对照研究(749名参与者:387例PM病例,362例对照)和一项嵌套病例对照欧洲癌症与营养前瞻性调查(EPIC)-Meso研究(268名参与者:134例临床前PM病例,134例匹配对照),在EPIC队列中开发并评估了多基因风险评分(PRS)和甲基化风险评分(MRS)。在回顾性病例对照研究中,全基因组关联分析确定了pm相关变异。PRS (1123 snp)与p |0.10|, FDR p
{"title":"Integrating polygenic and methylation risk scores for pleural mesothelioma risk stratification.","authors":"Khadija Sana Hafeez, Carla Debernardi, Alessandra Allione, Elton Jalis Herman, Simonetta Guarrera, Daniela Ferrante, Anna Aspesi, Marika Sculco, Marta La Vecchia, Carlotta Sacerdote, Federica Grosso, Christina M Lill, Giovanna Masala, Marcela Guevara, Matthias B Schulze, Salvatore Panico, Yaszan Asgari, Seehyun Park, Giovanna Tagliabue, Anne Tjønneland, Antonio Agudo, Elisabete Weiderpass, Corrado Magnani, Irma Dianzani, Paolo Vineis, Elisabetta Casalone, Giuseppe Matullo","doi":"10.1002/ijc.70316","DOIUrl":"https://doi.org/10.1002/ijc.70316","url":null,"abstract":"<p><p>Pleural mesothelioma (PM) is a lethal cancer primarily caused by asbestos exposure. Not all exposed individuals develop PM, suggesting the involvement of additional factors. This underscores the need for robust predictive models integrating biomarkers from multi-omic domains to improve risk stratification and early detection. We developed and evaluated polygenic risk scores (PRS) and methylation risk scores (MRS) using a retrospective case-control study (749 participants: 387 PM cases, 362 controls) and a nested case-control European Prospective Investigation into Cancer and Nutrition (EPIC)-Meso study (268 participants: 134 preclinical PM cases, 134 matched controls) within the EPIC cohort. Genome-wide association analyses in the retrospective case-control study identified PM-associated variants. The PRS (1123 SNPs with p < 0.001) in the retrospective training subset stratified disease risk in the test set (ORs 3.46-9.54 across top percentiles) and improved model discrimination (AUC = 0.75 vs. 0.71 in baseline model, p = 0.04). In EPIC-Meso, PRS performance was limited (AUC = 0.52). External validation in the UK-Biobank (UKBB) confirmed a modest but consistent association with PM-risk. A Meta-PRS derived from the UKBB-FinnGen meta-analysis replicated this trend in the full retrospective dataset, showing higher OR across top percentiles (2.5-12.3) and improved discrimination (AUC 0.74 vs. 0.72, p = 0.016). MRS, with 68 differentially methylated CpGs (effect-size >|0.10|, FDR p < 0.05) in the retrospective training set, increased the AUC from 0.66 to 0.85 (p < 0.001) in the test set and from 0.51 to 0.62 in EPIC-Meso. PRS was most predictive in low-exposure groups, while MRS remained robust across exposure levels. Combined PRS-MRS models improved discrimination. Integrating multi-omic biomarkers can enhance PM-risk stratification and support earlier, targeted interventions in high-risk asbestos-exposed groups.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145861432","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}
Timothy Mueller, Flavio Vasella, Julia Velz, Stefanos Voglis, Kevin Akeret, Luis Padevit, Morton Schubert, Jonathan Weller, Sarah Brüningk, Elisabeth Rushing, Johannes Sarnthein, Dorothee Gramatzki, Levin Häni, Andreas Raabe, Anna M Zeitlberger, Oliver Bozinov, Emilie Le Rhun, Michael Weller, Luca Regli, Marian C Neidert
Conditional survival provides insights into the evolution of prognosis over time and reveals changing associations of prognostic factors during disease progression. Data on the temporal evolution of prognostic factors in glioblastoma remain scarce. We analyzed 315 patients with IDH-wildtype glioblastoma from a prospectively collected registry (01/2008-06/2017). Our primary outcome was 12-month conditional survival (CS), defined as the probability of surviving the next 12 months given survival for "s" months. This analysis was conducted at five landmarks (s = 0, 6, 12, 18, 24) for baseline prognostic factors, including tumor volume compartments. 12-month conditional survival estimates at s = 0, 6, 12, 18, and 24 months from diagnosis were 0.51 (95% CI 0.45-0.56), 0.46 (95% CI 0.39-0.52), 0.41 (95% CI 0.33-0.49), 0.43 (95% CI 0.33-0.52), and 0.56 (95% CI 0.42-0.67), respectively. At diagnosis (s = 0), 12-month survival estimates varied significantly with age >60 at diagnosis, preoperative tumor rim volume >20 cm3, absence of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, postoperative KPS ≥70, residual postoperative tumor >1 cm3, or biopsy only. Residual tumor volume mainly influences survival in the initial months following surgery, while MGMT promoter methylation and age remain significant predictors beyond this period. These findings may refine stratification strategies in recurrent glioblastoma trials.
条件生存提供了对预后随时间演变的见解,并揭示了疾病进展过程中预后因素的变化关联。关于胶质母细胞瘤预后因素的时间演变的数据仍然很少。我们分析了来自前瞻性登记的315例idh野生型胶质母细胞瘤患者(2008年1月- 2017年6月)。我们的主要终点是12个月的条件生存(CS),定义为在生存期为“s”个月的情况下,未来12个月存活的概率。该分析在5个里程碑(s = 0、6、12、18、24)进行,以确定包括肿瘤体积区室在内的基线预后因素。诊断后0、6、12、18和24个月的条件生存估计分别为0.51 (95% CI 0.45-0.56)、0.46 (95% CI 0.39-0.52)、0.41 (95% CI 0.33-0.49)、0.43 (95% CI 0.33-0.52)和0.56 (95% CI 0.42-0.67)。诊断时(s = 0),诊断时年龄bbb60,术前肿瘤边缘体积>20 cm3, o6 -甲基鸟嘌呤- dna甲基转移酶(MGMT)启动子甲基化缺失,术后KPS≥70,术后残留肿瘤>1 cm3,或仅活检,12个月生存率估计差异显著。残留肿瘤体积主要影响手术后最初几个月的生存,而MGMT启动子甲基化和年龄仍然是这一时期后的重要预测因素。这些发现可以完善复发性胶质母细胞瘤试验的分层策略。
{"title":"Conditional survival in glioblastoma: The evolution of prognostic factors over time.","authors":"Timothy Mueller, Flavio Vasella, Julia Velz, Stefanos Voglis, Kevin Akeret, Luis Padevit, Morton Schubert, Jonathan Weller, Sarah Brüningk, Elisabeth Rushing, Johannes Sarnthein, Dorothee Gramatzki, Levin Häni, Andreas Raabe, Anna M Zeitlberger, Oliver Bozinov, Emilie Le Rhun, Michael Weller, Luca Regli, Marian C Neidert","doi":"10.1002/ijc.70285","DOIUrl":"10.1002/ijc.70285","url":null,"abstract":"<p><p>Conditional survival provides insights into the evolution of prognosis over time and reveals changing associations of prognostic factors during disease progression. Data on the temporal evolution of prognostic factors in glioblastoma remain scarce. We analyzed 315 patients with IDH-wildtype glioblastoma from a prospectively collected registry (01/2008-06/2017). Our primary outcome was 12-month conditional survival (CS), defined as the probability of surviving the next 12 months given survival for \"s\" months. This analysis was conducted at five landmarks (s = 0, 6, 12, 18, 24) for baseline prognostic factors, including tumor volume compartments. 12-month conditional survival estimates at s = 0, 6, 12, 18, and 24 months from diagnosis were 0.51 (95% CI 0.45-0.56), 0.46 (95% CI 0.39-0.52), 0.41 (95% CI 0.33-0.49), 0.43 (95% CI 0.33-0.52), and 0.56 (95% CI 0.42-0.67), respectively. At diagnosis (s = 0), 12-month survival estimates varied significantly with age >60 at diagnosis, preoperative tumor rim volume >20 cm<sup>3</sup>, absence of O<sup>6</sup>-methylguanine-DNA methyltransferase (MGMT) promoter methylation, postoperative KPS ≥70, residual postoperative tumor >1 cm<sup>3</sup>, or biopsy only. Residual tumor volume mainly influences survival in the initial months following surgery, while MGMT promoter methylation and age remain significant predictors beyond this period. These findings may refine stratification strategies in recurrent glioblastoma trials.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145861473","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}
Panpan Zhang, Miao Zhang, Yakun Wang, Lin Shen, Ming Lu
This single-center, open-label, single-arm phase II trial (NCT05165407) aimed to evaluate the efficacy and safety of surufatinib (250 mg orally once daily) combined with sintilimab (200 mg intravenously every 3 weeks) and IBI310 (1 mg/kg intravenously every 6 weeks) in patients with advanced high-grade neuroendocrine neoplasms (HG-NENs). The primary endpoint was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. As of March 28, 2025, 24 patients with measurable baseline lesions and at least one post-treatment tumor assessment were included in the efficacy-evaluable analysis set. The ORR was 37.5% (95% confidence interval [CI]: 18.8-59.4); DCR, 79.2% (95% CI: 57.8-92.9); and median DoR, 14.8 months. Among 31 treated patients in the full analysis set population, the median PFS was 3.81 months (95% CI: 2.79-4.50), and the median OS was 13.44 months (95% CI: 10.28-not estimable). Subgroup analyses showed improved response in patients with the following characteristics: female sex, age <55 years, ECOG performance status of 1, received ≤1 prior treatment line, without liver metastases, and <2 metastatic sites. Treatment-related adverse events (TRAEs) occurred in 96.8% of patients; 45.2% experienced grade ≥3 TRAEs. Among them, 71.0% experienced TRAEs attributed to sintilimab/IBI310, and 87.1% to surufatinib. Serious adverse events occurred in 45.2% of patients. These findings suggest that surufatinib, IBI310, and sintilimab may offer clinical benefit with manageable toxicity in patients with advanced HG-NENs.
{"title":"Surufatinib combined with sintilimab and IBI310 for the treatment of high-grade advanced-neuroendocrine neoplasms: A single arm, open-label, single-center, phase II study.","authors":"Panpan Zhang, Miao Zhang, Yakun Wang, Lin Shen, Ming Lu","doi":"10.1002/ijc.70311","DOIUrl":"https://doi.org/10.1002/ijc.70311","url":null,"abstract":"<p><p>This single-center, open-label, single-arm phase II trial (NCT05165407) aimed to evaluate the efficacy and safety of surufatinib (250 mg orally once daily) combined with sintilimab (200 mg intravenously every 3 weeks) and IBI310 (1 mg/kg intravenously every 6 weeks) in patients with advanced high-grade neuroendocrine neoplasms (HG-NENs). The primary endpoint was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. As of March 28, 2025, 24 patients with measurable baseline lesions and at least one post-treatment tumor assessment were included in the efficacy-evaluable analysis set. The ORR was 37.5% (95% confidence interval [CI]: 18.8-59.4); DCR, 79.2% (95% CI: 57.8-92.9); and median DoR, 14.8 months. Among 31 treated patients in the full analysis set population, the median PFS was 3.81 months (95% CI: 2.79-4.50), and the median OS was 13.44 months (95% CI: 10.28-not estimable). Subgroup analyses showed improved response in patients with the following characteristics: female sex, age <55 years, ECOG performance status of 1, received ≤1 prior treatment line, without liver metastases, and <2 metastatic sites. Treatment-related adverse events (TRAEs) occurred in 96.8% of patients; 45.2% experienced grade ≥3 TRAEs. Among them, 71.0% experienced TRAEs attributed to sintilimab/IBI310, and 87.1% to surufatinib. Serious adverse events occurred in 45.2% of patients. These findings suggest that surufatinib, IBI310, and sintilimab may offer clinical benefit with manageable toxicity in patients with advanced HG-NENs.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848429","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}
This descriptive analysis evaluates design strategies, regulatory outcomes, and temporal trends in oncology accelerated approvals (AAs) over three decades, comparing solid tumors with hematologic malignancies. We retrospectively reviewed publicly available U.S. Food and Drug Administration (FDA) data on oncology drugs granted AA between December 1992 and January 2025, focusing on those with completed post-approval assessments. Key measures included trial design, endpoints, conversion and withdrawal rates, and time to regulatory resolution. Of 204 AAs representing 204 drug-indication pairs (across 133 drugs), 138 had completed post-approval assessments; 77.5% converted to regular approval, 22.5% were withdrawn. Solid tumors accounted for 63% (87/138) of AAs, and had higher conversion rates to regular approvals compared to hematologic malignancies (82% vs. 71%, respectively). Withdrawals were more frequent in hematologic malignancies compared to solid tumors (29% vs. 18%, respectively). Orphan drug designation and post-approval label modifications were more common in hematologic malignancies than solid tumors (76% vs. 45%, and 18% vs. 11%, respectively). Randomized controlled trials (RCTs) drove most successful conversions (63%). Among 105 AA trials for solid tumors, overall response rate (ORR) was the primary endpoint in 74%, with progression-free survival (PFS) and overall survival (OS) in 13% and 9% AAs, respectively. Hematologic trials favored ORR (33%) and disease-specific endpoints. The most common AA → confirmatory pathway was ORR → PFS (46%). OS as a confirmatory endpoint after surrogate-based AA was linked to higher withdrawal rates, whereas consistent endpoints (e.g., OS → OS) had none. RCTs and aligned endpoints drive successful oncology AA conversions, while surrogate-confirmed OS often precedes withdrawal.
{"title":"Accelerated approvals in oncology: Trial design strategies and insights driving successful regulatory outcomes across three decades.","authors":"Rohini Sharma, Anamika Gulati, Kanwaljit Chopra","doi":"10.1002/ijc.70317","DOIUrl":"https://doi.org/10.1002/ijc.70317","url":null,"abstract":"<p><p>This descriptive analysis evaluates design strategies, regulatory outcomes, and temporal trends in oncology accelerated approvals (AAs) over three decades, comparing solid tumors with hematologic malignancies. We retrospectively reviewed publicly available U.S. Food and Drug Administration (FDA) data on oncology drugs granted AA between December 1992 and January 2025, focusing on those with completed post-approval assessments. Key measures included trial design, endpoints, conversion and withdrawal rates, and time to regulatory resolution. Of 204 AAs representing 204 drug-indication pairs (across 133 drugs), 138 had completed post-approval assessments; 77.5% converted to regular approval, 22.5% were withdrawn. Solid tumors accounted for 63% (87/138) of AAs, and had higher conversion rates to regular approvals compared to hematologic malignancies (82% vs. 71%, respectively). Withdrawals were more frequent in hematologic malignancies compared to solid tumors (29% vs. 18%, respectively). Orphan drug designation and post-approval label modifications were more common in hematologic malignancies than solid tumors (76% vs. 45%, and 18% vs. 11%, respectively). Randomized controlled trials (RCTs) drove most successful conversions (63%). Among 105 AA trials for solid tumors, overall response rate (ORR) was the primary endpoint in 74%, with progression-free survival (PFS) and overall survival (OS) in 13% and 9% AAs, respectively. Hematologic trials favored ORR (33%) and disease-specific endpoints. The most common AA → confirmatory pathway was ORR → PFS (46%). OS as a confirmatory endpoint after surrogate-based AA was linked to higher withdrawal rates, whereas consistent endpoints (e.g., OS → OS) had none. RCTs and aligned endpoints drive successful oncology AA conversions, while surrogate-confirmed OS often precedes withdrawal.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848603","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}