Anlan Cao, Denise A Esserman, Brenda Cartmel, Melinda L Irwin, Leah M Ferrucci
Background: Research on diet quality and ovarian cancer is limited. We examined the association between diet quality and ovarian cancer risk and survival in a large prospective cohort.
Methods: We used data from women in the prospective National Institutes of Health-AARP Diet and Health Study enrolled from 1995 to 1996 who were aged 50-71 years at baseline with follow-up through December 31, 2017. Participants completed a 124-item food frequency questionnaire at baseline, and diet quality was assessed via the Healthy Eating Index-2015, the alternate Mediterranean diet score, and the Dietary Approaches to Stop Hypertension score. Primary outcomes were first primary epithelial ovarian cancer diagnosis from cancer registry data and among those diagnosed with ovarian cancer all-cause mortality. We used a semi-Markov multistate model with Cox proportional hazards regression to account for semicompeting events.
Results: Among 150 643 participants with a median follow-up time of 20.5 years, 1107 individuals were diagnosed with a first primary epithelial ovarian cancer. There was no evidence of an association between diet quality and ovarian cancer risk. Among those diagnosed with epithelial ovarian cancer, 893 deaths occurred with a median survival of 2.5 years. Better prediagnosis diet quality, according to the Healthy Eating Index-2015 (quintile 5 vs quintile 1: hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.60 to 0.93) and alternate Mediterranean diet score (quintile 5 vs quintile 1: HR = 0.68, 95% CI = 0.53 to 0.87), was associated with lower all-cause mortality. There was no evidence of an association between Dietary Approaches to Stop Hypertension score and all-cause mortality.
Conclusions: Better prediagnosis diet quality was associated with lower all-cause mortality after ovarian cancer diagnosis but was not associated with ovarian cancer risk.
{"title":"Association between diet quality and ovarian cancer risk and survival.","authors":"Anlan Cao, Denise A Esserman, Brenda Cartmel, Melinda L Irwin, Leah M Ferrucci","doi":"10.1093/jnci/djae040","DOIUrl":"10.1093/jnci/djae040","url":null,"abstract":"<p><strong>Background: </strong>Research on diet quality and ovarian cancer is limited. We examined the association between diet quality and ovarian cancer risk and survival in a large prospective cohort.</p><p><strong>Methods: </strong>We used data from women in the prospective National Institutes of Health-AARP Diet and Health Study enrolled from 1995 to 1996 who were aged 50-71 years at baseline with follow-up through December 31, 2017. Participants completed a 124-item food frequency questionnaire at baseline, and diet quality was assessed via the Healthy Eating Index-2015, the alternate Mediterranean diet score, and the Dietary Approaches to Stop Hypertension score. Primary outcomes were first primary epithelial ovarian cancer diagnosis from cancer registry data and among those diagnosed with ovarian cancer all-cause mortality. We used a semi-Markov multistate model with Cox proportional hazards regression to account for semicompeting events.</p><p><strong>Results: </strong>Among 150 643 participants with a median follow-up time of 20.5 years, 1107 individuals were diagnosed with a first primary epithelial ovarian cancer. There was no evidence of an association between diet quality and ovarian cancer risk. Among those diagnosed with epithelial ovarian cancer, 893 deaths occurred with a median survival of 2.5 years. Better prediagnosis diet quality, according to the Healthy Eating Index-2015 (quintile 5 vs quintile 1: hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.60 to 0.93) and alternate Mediterranean diet score (quintile 5 vs quintile 1: HR = 0.68, 95% CI = 0.53 to 0.87), was associated with lower all-cause mortality. There was no evidence of an association between Dietary Approaches to Stop Hypertension score and all-cause mortality.</p><p><strong>Conclusions: </strong>Better prediagnosis diet quality was associated with lower all-cause mortality after ovarian cancer diagnosis but was not associated with ovarian cancer risk.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":null,"pages":null},"PeriodicalIF":9.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11223874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nirmal Choradia, Fatima Karzai, Ryan Nipp, Abdul Rafeh Naqash, James L Gulley, Charalampos S Floudas
Background: We described participant demographics for National Cancer Institute (NCI) clinical trials at the clinical center (NCI-CC participants) of the National Institutes of Health to identify enrollment disparities.
Methods: We analyzed NCI-CC data from 2005 to 2020, calculated enrollment fractions, compared with the US cancer population represented by the Surveillance, Epidemiology, and End Results cancer incidence data (2018) and the Cancer in North America database (2018), and compared further with clinical trial disparities data from the NCI Community Oncology Research Program and National Clinical Trials Network (2005-2019), and from ClinicalTrials.gov (2003-2016).
Results: NCI-CC (38 531 participants) had higher enrollment fractions for older adults (8.5%), male (5.6%), non-Hispanic (5.1%), and Black or African American (5.3%) participants; lower women proportion across race and ethnicity; and fewer female sex-specific cancer (6.8%) than male sex-specific cancer (11.7%) participants. NCI-CC had lower median age than Surveillance, Epidemiology, and End Results (54.0 vs 65.4); more Black or African American participants (12.0% vs 11.1%); and fewer women (41.7% vs 49.5%), White (76.1% vs 80.5%), Asian or Pacific Islander (4.6% vs 6.0%), American Indian or Alaska Native (0.3% vs 0.5%), and Hispanic participants (7.1% vs 13%). NCI-CC had more Black or African American and Asian or Pacific Islander participants; fewer Hispanic participants than the NCI Community Oncology Research Program and National Clinical Trials Network; more Black or African American and Hispanic participants; fewer Asian or Pacific Islander participants than ClinicalTrials.gov data. Improvement was noted for NCI-CC (older adults, Black or African American, Asian or Pacific Islander, Hispanic participants).
Conclusion: We found lower representation of older adults, women, Asian or Pacific Islander, American Indian or Alaska Native, and Hispanic participants vs the US cancer population and higher representation of Black or African American vs US cancer population and oncology clinical trials. Multifaceted efforts are underway to reduce disparities in cancer clinical trials at the NCI-CC.
背景:我们描述了美国国立卫生研究院(NIH)临床中心(CC)的美国国立癌症研究所(NCI)临床试验参与者(NCI-CC参与者)的人口统计学特征,以确定入学差异:我们分析了2005-2020年的NCI-CC数据,计算了入组比例(EF),并与监测、流行病学和最终结果(SEER)癌症发病率数据(2018年)和北美癌症(CiNA)数据库(2018年)所代表的美国癌症人群进行了比较,还与NCI的社区肿瘤学研究计划(NCORP)和国家临床试验网络(NCTN)(2005-2019年)以及ClinicalTrials.gov(2003-2016年)的临床试验差异数据进行了比较:NCI-CC(38,531 名参与者)中,老年人(OA)(8.5%)、男性(5.6%)、非西班牙裔(5.1%)、黑人/非洲裔美国人(AA)(5.3%)参与者的 EF 较高;不同种族和族裔的女性比例较低;女性特定性别癌症参与者(6.8%)少于男性特定性别癌症参与者(11.7%)。NCI-CC的中位年龄低于SEER(54.0 vs 65.4),AA参与者较多(12.0% vs 11.1%),女性(41.7% vs 49.5%)、白人(76.1% vs 80.5%)、亚太裔(AP)(4.6% vs 6.0%)、美国印第安人/阿拉斯加原住民(AI)(0.3% vs 0.5%)和西班牙裔参与者(7.1% vs 13%)较少。与 NCORP 和 NCTN 相比,NCI-CC 的 AA、AP 参与者较多,西班牙裔参与者较少;与 ClinicalTrials.gov 数据相比,AA、西班牙裔参与者较多,AP 参与者较少。NCI-CC的情况有所改善(OA、AA、AP、西班牙裔参与者):我们发现,OA、女性、AP、AI、西班牙裔参与人数低于美国癌症人口,AA参与人数高于美国癌症人口和肿瘤临床试验。国家癌症临床试验中心(NCI-CC)正在开展多方面的努力,以减少癌症临床试验中的不平等现象。
{"title":"Increasing diversity in clinical trials: demographic trends at the National Cancer Institute, 2005-2020.","authors":"Nirmal Choradia, Fatima Karzai, Ryan Nipp, Abdul Rafeh Naqash, James L Gulley, Charalampos S Floudas","doi":"10.1093/jnci/djae018","DOIUrl":"10.1093/jnci/djae018","url":null,"abstract":"<p><strong>Background: </strong>We described participant demographics for National Cancer Institute (NCI) clinical trials at the clinical center (NCI-CC participants) of the National Institutes of Health to identify enrollment disparities.</p><p><strong>Methods: </strong>We analyzed NCI-CC data from 2005 to 2020, calculated enrollment fractions, compared with the US cancer population represented by the Surveillance, Epidemiology, and End Results cancer incidence data (2018) and the Cancer in North America database (2018), and compared further with clinical trial disparities data from the NCI Community Oncology Research Program and National Clinical Trials Network (2005-2019), and from ClinicalTrials.gov (2003-2016).</p><p><strong>Results: </strong>NCI-CC (38 531 participants) had higher enrollment fractions for older adults (8.5%), male (5.6%), non-Hispanic (5.1%), and Black or African American (5.3%) participants; lower women proportion across race and ethnicity; and fewer female sex-specific cancer (6.8%) than male sex-specific cancer (11.7%) participants. NCI-CC had lower median age than Surveillance, Epidemiology, and End Results (54.0 vs 65.4); more Black or African American participants (12.0% vs 11.1%); and fewer women (41.7% vs 49.5%), White (76.1% vs 80.5%), Asian or Pacific Islander (4.6% vs 6.0%), American Indian or Alaska Native (0.3% vs 0.5%), and Hispanic participants (7.1% vs 13%). NCI-CC had more Black or African American and Asian or Pacific Islander participants; fewer Hispanic participants than the NCI Community Oncology Research Program and National Clinical Trials Network; more Black or African American and Hispanic participants; fewer Asian or Pacific Islander participants than ClinicalTrials.gov data. Improvement was noted for NCI-CC (older adults, Black or African American, Asian or Pacific Islander, Hispanic participants).</p><p><strong>Conclusion: </strong>We found lower representation of older adults, women, Asian or Pacific Islander, American Indian or Alaska Native, and Hispanic participants vs the US cancer population and higher representation of Black or African American vs US cancer population and oncology clinical trials. Multifaceted efforts are underway to reduce disparities in cancer clinical trials at the NCI-CC.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":null,"pages":null},"PeriodicalIF":9.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11223850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139905682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jennifer W Mack, Colin Cernik, Lanfang Xu, Cecile A Laurent, Lauren Fisher, Nancy Cannizzaro, Julie Munneke, Robert M Cooper, Joshua R Lakin, Corey M Schwartz, Mallory Casperson, Andrea Altschuler, Lori Wiener, Lawrence H Kushi, Chun R Chao, Hajime Uno
Background: Adolescents and young adults frequently receive chemotherapy near death. We know less about the use of targeted agents and immunotherapy or trends over time.
Methods: We conducted a retrospective cohort study of 1836 adolescents and young adults with cancer who died between 2009 and 2019 after receiving care at 1 of 3 sites (Dana-Farber Cancer Institute, Kaiser Permanente Northern California, and Kaiser Permanente Southern California). We reviewed electronic health data and medical records to examine use of cancer-directed therapy in the last 90 days of life, including chemotherapy, targeted therapy, immunotherapy, and investigational drugs.
Results: Over the study period, 35% of adolescents and young adults received chemotherapy in the last 90 days of life; 24% received targeted therapy, 7% immunotherapy, and 5% investigational drugs. Additionally, 56% received at least 1 form of systemic cancer-directed therapy in the last 90 days of life. After adjustment for patient sex, race, ethnicity, age, site of care, diagnosis, and years from diagnosis to death, the proportion of adolescents and young adults receiving targeted therapy (odds ratio [OR] = 1.05 per year of death, 95% confidence interval [CI] = 1.02 to 1.10; P = .006), immunotherapy (OR = 1.27, 95% CI = 1.18 to 1.38; P < .0001), and any cancer-directed therapy (OR = 1.04, 95% CI = 1.01 to 1.08; P = .01) in the last 90 days of life increased over time.
Conclusions: More than half of adolescents and young adults receive cancer therapy in the last 90 days of life, and use of novel agents such as targeted therapy and immunotherapy is increasing over time. Although some adolescents and young adults may wish to continue cancer therapy while living with advanced disease, efforts are needed to ensure that use of cancer-directed therapy meets preferences of adolescents and young adults approaching death.
{"title":"Use of cancer-directed therapy at the end of life among adolescents and young adults.","authors":"Jennifer W Mack, Colin Cernik, Lanfang Xu, Cecile A Laurent, Lauren Fisher, Nancy Cannizzaro, Julie Munneke, Robert M Cooper, Joshua R Lakin, Corey M Schwartz, Mallory Casperson, Andrea Altschuler, Lori Wiener, Lawrence H Kushi, Chun R Chao, Hajime Uno","doi":"10.1093/jnci/djae038","DOIUrl":"10.1093/jnci/djae038","url":null,"abstract":"<p><strong>Background: </strong>Adolescents and young adults frequently receive chemotherapy near death. We know less about the use of targeted agents and immunotherapy or trends over time.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of 1836 adolescents and young adults with cancer who died between 2009 and 2019 after receiving care at 1 of 3 sites (Dana-Farber Cancer Institute, Kaiser Permanente Northern California, and Kaiser Permanente Southern California). We reviewed electronic health data and medical records to examine use of cancer-directed therapy in the last 90 days of life, including chemotherapy, targeted therapy, immunotherapy, and investigational drugs.</p><p><strong>Results: </strong>Over the study period, 35% of adolescents and young adults received chemotherapy in the last 90 days of life; 24% received targeted therapy, 7% immunotherapy, and 5% investigational drugs. Additionally, 56% received at least 1 form of systemic cancer-directed therapy in the last 90 days of life. After adjustment for patient sex, race, ethnicity, age, site of care, diagnosis, and years from diagnosis to death, the proportion of adolescents and young adults receiving targeted therapy (odds ratio [OR] = 1.05 per year of death, 95% confidence interval [CI] = 1.02 to 1.10; P = .006), immunotherapy (OR = 1.27, 95% CI = 1.18 to 1.38; P < .0001), and any cancer-directed therapy (OR = 1.04, 95% CI = 1.01 to 1.08; P = .01) in the last 90 days of life increased over time.</p><p><strong>Conclusions: </strong>More than half of adolescents and young adults receive cancer therapy in the last 90 days of life, and use of novel agents such as targeted therapy and immunotherapy is increasing over time. Although some adolescents and young adults may wish to continue cancer therapy while living with advanced disease, efforts are needed to ensure that use of cancer-directed therapy meets preferences of adolescents and young adults approaching death.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":null,"pages":null},"PeriodicalIF":9.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11223859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paola Gonzalo-Encabo, Alexi Vasbinder, Jennifer W Bea, Kerryn W Reding, Deepika Laddu, Michael J LaMonte, Marcia L Stefanick, Candyce H Kroenke, Su Yon Jung, Aladdin H Shadyab, Michelle J Naughton, Manali I Patel, Juhua Luo, Hailey R Banack, Yangbo Sun, Michael S Simon, Christina M Dieli-Conwright
Background: Postmenopausal women with cancer experience an accelerated physical dysfunction beyond what is expected through aging alone due to cancer and its treatments. The aim of this study was to determine whether declines in physical function after cancer diagnosis are associated with all-cause mortality and cancer-specific mortality.
Methods: This prospective cohort study included 8068 postmenopausal women enrolled in the Women's Health Initiative with a cancer diagnosis and who had physical function assessed within 1 year of that diagnosis. Self-reported physical function was measured using the 10-item physical function subscale of the 36-Item Short Form Health Survey. Cause of death was determined by medical record review, with central adjudication and linkage to the National Death Index. Death was adjudicated through February 2022.
Results: Over a median follow-up of 7.7 years from cancer diagnosis, 3316 (41.1%) women died. Our results showed that for every 10% difference in the physical function score after cancer diagnosis versus pre-diagnosis, all-cause mortality and cancer-specific mortality were reduced by 12% (hazard ratio [HR] = 0.88, 95% confidence interval [95% CI] = 0.87 to 0.89 and HR = 0.88, 95% CI = 0.86 to 0.91, respectively). Further categorical analyses showed a significant dose-response relationship between postdiagnosis physical function categories and mortality outcomes (P < .001 for trend), where the median survival time for women in the lowest physical function quartile was 9.1 years (Interquartile range [IQR] = 8.6-10.6 years) compared with 18.4 years (IQR = 15.8-22.0 years) for women in the highest physical function quartile.
Conclusion: Postmenopausal women with low physical function after cancer diagnosis may be at higher risk of mortality from all causes and cancer-related mortality.
{"title":"Low physical function following cancer diagnosis is associated with higher mortality risk in postmenopausal women.","authors":"Paola Gonzalo-Encabo, Alexi Vasbinder, Jennifer W Bea, Kerryn W Reding, Deepika Laddu, Michael J LaMonte, Marcia L Stefanick, Candyce H Kroenke, Su Yon Jung, Aladdin H Shadyab, Michelle J Naughton, Manali I Patel, Juhua Luo, Hailey R Banack, Yangbo Sun, Michael S Simon, Christina M Dieli-Conwright","doi":"10.1093/jnci/djae055","DOIUrl":"10.1093/jnci/djae055","url":null,"abstract":"<p><strong>Background: </strong>Postmenopausal women with cancer experience an accelerated physical dysfunction beyond what is expected through aging alone due to cancer and its treatments. The aim of this study was to determine whether declines in physical function after cancer diagnosis are associated with all-cause mortality and cancer-specific mortality.</p><p><strong>Methods: </strong>This prospective cohort study included 8068 postmenopausal women enrolled in the Women's Health Initiative with a cancer diagnosis and who had physical function assessed within 1 year of that diagnosis. Self-reported physical function was measured using the 10-item physical function subscale of the 36-Item Short Form Health Survey. Cause of death was determined by medical record review, with central adjudication and linkage to the National Death Index. Death was adjudicated through February 2022.</p><p><strong>Results: </strong>Over a median follow-up of 7.7 years from cancer diagnosis, 3316 (41.1%) women died. Our results showed that for every 10% difference in the physical function score after cancer diagnosis versus pre-diagnosis, all-cause mortality and cancer-specific mortality were reduced by 12% (hazard ratio [HR] = 0.88, 95% confidence interval [95% CI] = 0.87 to 0.89 and HR = 0.88, 95% CI = 0.86 to 0.91, respectively). Further categorical analyses showed a significant dose-response relationship between postdiagnosis physical function categories and mortality outcomes (P < .001 for trend), where the median survival time for women in the lowest physical function quartile was 9.1 years (Interquartile range [IQR] = 8.6-10.6 years) compared with 18.4 years (IQR = 15.8-22.0 years) for women in the highest physical function quartile.</p><p><strong>Conclusion: </strong>Postmenopausal women with low physical function after cancer diagnosis may be at higher risk of mortality from all causes and cancer-related mortality.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":null,"pages":null},"PeriodicalIF":9.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11223816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140049564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: We quantified the pathological spatial intratumor heterogeneity of programmed death-ligand 1 (PD-L1) expression and investigated its relevance to patient outcomes in surgically resected non-small cell lung carcinoma (NSCLC).
Methods: This study enrolled 239 consecutive surgically resected NSCLC specimens of pathological stage IIA-IIIB. To characterize the spatial intratumor heterogeneity of PD-L1 expression in NSCLC tissues, we developed a mathematical model based on texture image analysis and determined the spatial heterogeneity index of PD-L1 for each tumor. The correlation between the spatial heterogeneity index of PD-L1 values and clinicopathological characteristics, including prognosis, was analyzed. Furthermore, an independent cohort of 70 cases was analyzed for model validation.
Results: Clinicopathological analysis showed correlations between high spatial heterogeneity index of PD-L1 values and histological subtype (squamous cell carcinoma; P < .001) and vascular invasion (P = .004). Survival analysis revealed that patients with high spatial heterogeneity index of PD-L1 values presented a significantly worse recurrence-free rate than those with low spatial heterogeneity index of PD-L1 values (5-year recurrence-free survival [RFS] = 26.3% vs 47.1%, P < .005). The impact of spatial heterogeneity index of PD-L1 on cancer survival rates was verified through validation in an independent cohort. Additionally, high spatial heterogeneity index of PD-L1 values were associated with tumor recurrence in squamous cell carcinoma (5-year RFS = 29.2% vs 52.8%, P < .05) and adenocarcinoma (5-year RFS = 19.6% vs 43.0%, P < .01). Moreover, we demonstrated that a high spatial heterogeneity index of PD-L1 value was an independent risk factor for tumor recurrence.
Conclusions: We presented an image analysis model to quantify the spatial intratumor heterogeneity of protein expression in tumor tissues. This model demonstrated that the spatial intratumor heterogeneity of PD-L1 expression in surgically resected NSCLC predicts poor patient outcomes.
{"title":"Spatial intratumor heterogeneity of programmed death-ligand 1 expression predicts poor prognosis in resected non-small cell lung cancer.","authors":"Yusuke Nagasaki, Tetsuro Taki, Kotaro Nomura, Kenta Tane, Tomohiro Miyoshi, Joji Samejima, Keiju Aokage, Seiyu Jeong-Yoo Ohtani-Kim, Motohiro Kojima, Shingo Sakashita, Naoya Sakamoto, Shumpei Ishikawa, Kenji Suzuki, Masahiro Tsuboi, Genichiro Ishii","doi":"10.1093/jnci/djae053","DOIUrl":"10.1093/jnci/djae053","url":null,"abstract":"<p><strong>Background: </strong>We quantified the pathological spatial intratumor heterogeneity of programmed death-ligand 1 (PD-L1) expression and investigated its relevance to patient outcomes in surgically resected non-small cell lung carcinoma (NSCLC).</p><p><strong>Methods: </strong>This study enrolled 239 consecutive surgically resected NSCLC specimens of pathological stage IIA-IIIB. To characterize the spatial intratumor heterogeneity of PD-L1 expression in NSCLC tissues, we developed a mathematical model based on texture image analysis and determined the spatial heterogeneity index of PD-L1 for each tumor. The correlation between the spatial heterogeneity index of PD-L1 values and clinicopathological characteristics, including prognosis, was analyzed. Furthermore, an independent cohort of 70 cases was analyzed for model validation.</p><p><strong>Results: </strong>Clinicopathological analysis showed correlations between high spatial heterogeneity index of PD-L1 values and histological subtype (squamous cell carcinoma; P < .001) and vascular invasion (P = .004). Survival analysis revealed that patients with high spatial heterogeneity index of PD-L1 values presented a significantly worse recurrence-free rate than those with low spatial heterogeneity index of PD-L1 values (5-year recurrence-free survival [RFS] = 26.3% vs 47.1%, P < .005). The impact of spatial heterogeneity index of PD-L1 on cancer survival rates was verified through validation in an independent cohort. Additionally, high spatial heterogeneity index of PD-L1 values were associated with tumor recurrence in squamous cell carcinoma (5-year RFS = 29.2% vs 52.8%, P < .05) and adenocarcinoma (5-year RFS = 19.6% vs 43.0%, P < .01). Moreover, we demonstrated that a high spatial heterogeneity index of PD-L1 value was an independent risk factor for tumor recurrence.</p><p><strong>Conclusions: </strong>We presented an image analysis model to quantify the spatial intratumor heterogeneity of protein expression in tumor tissues. This model demonstrated that the spatial intratumor heterogeneity of PD-L1 expression in surgically resected NSCLC predicts poor patient outcomes.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":null,"pages":null},"PeriodicalIF":9.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nosakhare Paul Ilerhunmwuwa, Abul Hasan Shadali Abdul Khader, Calvin Smith, Edward R Scheffer Cliff, Christopher M Booth, Evevanne Hottel, Muhammad Aziz, Wade Lee-Smith, Aaron Goodman, Rajshekhar Chakraborty, Ghulam Rehman Mohyuddin
Background: Prior systematic reviews addressing the impact of diet on cancer outcomes have focused on specific dietary interventions. In this systematic review, we assessed all randomized controlled trials (RCTs) investigating dietary interventions for cancer patients, examining the range of interventions, endpoints, patient populations, and results.
Methods: This systematic review identified all RCTs conducted before January 2023 testing dietary interventions in patients with cancer. Assessed outcomes included quality of life, functional outcomes, clinical cancer measurements (eg, progression-free survival, response rates), overall survival, and translational endpoints (eg, inflammatory markers).
Results: In total, 252 RCTs were identified involving 31 067 patients. The median sample size was 71 (interquartile range 41 to 118), and 80 (32%) studies had a sample size greater than 100. Most trials (n = 184, 73%) were conducted in the adjuvant setting. Weight or body composition and translational endpoints were the most common primary endpoints (n = 64, 25%; n = 52, 21%, respectively). Direct cancer measurements and overall survival were primary endpoints in 20 (8%) and 7 (3%) studies, respectively. Eight trials with a primary endpoint of cancer measurement (40%) met their endpoint. Large trials in colon (n = 1429), breast (n = 3088), and prostate cancer (n = 478) each showed no effect of dietary interventions on endpoints measuring cancer.
Conclusion: Most RCTs of dietary interventions in cancer are small and measure nonclinical endpoints. Although only a small number of large RCTs have been conducted to date, these trials have not shown an improvement in cancer outcomes. Currently, there is limited evidence to support dietary interventions as a therapeutic tool in cancer care.
{"title":"Dietary interventions in cancer: a systematic review of all randomized controlled trials.","authors":"Nosakhare Paul Ilerhunmwuwa, Abul Hasan Shadali Abdul Khader, Calvin Smith, Edward R Scheffer Cliff, Christopher M Booth, Evevanne Hottel, Muhammad Aziz, Wade Lee-Smith, Aaron Goodman, Rajshekhar Chakraborty, Ghulam Rehman Mohyuddin","doi":"10.1093/jnci/djae051","DOIUrl":"10.1093/jnci/djae051","url":null,"abstract":"<p><strong>Background: </strong>Prior systematic reviews addressing the impact of diet on cancer outcomes have focused on specific dietary interventions. In this systematic review, we assessed all randomized controlled trials (RCTs) investigating dietary interventions for cancer patients, examining the range of interventions, endpoints, patient populations, and results.</p><p><strong>Methods: </strong>This systematic review identified all RCTs conducted before January 2023 testing dietary interventions in patients with cancer. Assessed outcomes included quality of life, functional outcomes, clinical cancer measurements (eg, progression-free survival, response rates), overall survival, and translational endpoints (eg, inflammatory markers).</p><p><strong>Results: </strong>In total, 252 RCTs were identified involving 31 067 patients. The median sample size was 71 (interquartile range 41 to 118), and 80 (32%) studies had a sample size greater than 100. Most trials (n = 184, 73%) were conducted in the adjuvant setting. Weight or body composition and translational endpoints were the most common primary endpoints (n = 64, 25%; n = 52, 21%, respectively). Direct cancer measurements and overall survival were primary endpoints in 20 (8%) and 7 (3%) studies, respectively. Eight trials with a primary endpoint of cancer measurement (40%) met their endpoint. Large trials in colon (n = 1429), breast (n = 3088), and prostate cancer (n = 478) each showed no effect of dietary interventions on endpoints measuring cancer.</p><p><strong>Conclusion: </strong>Most RCTs of dietary interventions in cancer are small and measure nonclinical endpoints. Although only a small number of large RCTs have been conducted to date, these trials have not shown an improvement in cancer outcomes. Currently, there is limited evidence to support dietary interventions as a therapeutic tool in cancer care.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":null,"pages":null},"PeriodicalIF":9.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11223872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Randomized trials of the efficacy of multicancer early detection, by means of measurement of cell-free DNA and/or protein biomarkers in peripheral blood specimens, will attempt to document a difference in cancer mortality between persons assigned to intervention and control arms. Their ability to do so is limited by the relatively low rate of death from individual forms of cancer, the relatively low sensitivity of the tests currently being used, and the use of other cancer screening modalities among trial participants. However, if those same blood specimens also could be obtained from control arm participants in a given trial and then tested for the same markers, with results not known (or not made available) until the conclusion of follow-up for cancer mortality, it would be possible to compare mortality from given forms of cancer between test-positive individuals whose results were known and not known during the course of the trial. Such an analysis addresses the impact of a stimulus to offer targeted diagnostic testing, potentially leading to early treatment, against cancer mortality. Among persons who screen as positive, it should provide a relatively more sensitive means of gauging a possible mortality benefit resulting from multicancer screening.
通过测量外周血标本中的无细胞 DNA 和/或蛋白质生物标志物,对多种癌症早期检测的有效性进行随机试验,试图记录被分配到干预组和对照组的人在癌症死亡率方面的差异。由于个别癌症的死亡率相对较低、目前使用的检测灵敏度相对较低以及试验参与者使用其他癌症筛查方式,他们的能力受到了限制。不过,如果能从特定试验的对照组参与者那里获得相同的血液标本,然后进行相同标记物的检测,并且在癌症死亡率随访结束前不知道(或无法获得)检测结果,那么就有可能比较试验期间检测结果已知和未知的检测阳性者之间特定癌症的死亡率。这种分析针对的是提供有针对性诊断检测的刺激措施对癌症死亡率的影响,这种刺激措施有可能导致早期治疗。在筛查结果为阳性的人群中,它应能提供一种相对更灵敏的方法来衡量多种癌症筛查可能带来的死亡率益处。
{"title":"Randomized trials of multicancer screening tests: augmenting their ability to identify a genuine mortality benefit.","authors":"Noel S Weiss","doi":"10.1093/jnci/djae059","DOIUrl":"10.1093/jnci/djae059","url":null,"abstract":"<p><p>Randomized trials of the efficacy of multicancer early detection, by means of measurement of cell-free DNA and/or protein biomarkers in peripheral blood specimens, will attempt to document a difference in cancer mortality between persons assigned to intervention and control arms. Their ability to do so is limited by the relatively low rate of death from individual forms of cancer, the relatively low sensitivity of the tests currently being used, and the use of other cancer screening modalities among trial participants. However, if those same blood specimens also could be obtained from control arm participants in a given trial and then tested for the same markers, with results not known (or not made available) until the conclusion of follow-up for cancer mortality, it would be possible to compare mortality from given forms of cancer between test-positive individuals whose results were known and not known during the course of the trial. Such an analysis addresses the impact of a stimulus to offer targeted diagnostic testing, potentially leading to early treatment, against cancer mortality. Among persons who screen as positive, it should provide a relatively more sensitive means of gauging a possible mortality benefit resulting from multicancer screening.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":null,"pages":null},"PeriodicalIF":9.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11223825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140049565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Is it time to reconsider the role of upfront cytoreductive nephrectomy in metastatic renal cell carcinoma?","authors":"Avery E Braun, Maxwell V Meng","doi":"10.1093/jnci/djae099","DOIUrl":"10.1093/jnci/djae099","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":null,"pages":null},"PeriodicalIF":9.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Roshan Paudel, Andrea C Enzinger, Hajime Uno, Christine Cronin, Sandra L Wong, Don S Dizon, Hannah Hazard Jenkins, Jessica Bian, Raymond U Osarogiagbon, Roxanne E Jensen, Sandra A Mitchell, Deborah Schrag, Michael J Hassett
Background: Optimal methods for deploying electronic patient-reported outcomes to manage symptoms in routine oncologic practice remain uncertain. The electronic symptom management (eSyM) program asks chemotherapy and surgery patients to self-report 12 common symptoms regularly. Feedback from nurses and patients led to changing the recall period from the past 7 days to the past 24 hours.
Methods: Using questionnaires submitted during the 16 weeks surrounding the recall period change, we assessed the likelihood of reporting severe or moderate and severe symptoms across 12 common symptoms and separately for the 5 most prevalent symptoms. Interrupted time-series analyses modeled the effects of the change using generalized linear mixed-effects models. Surgery and chemotherapy cohorts were analyzed separately. Study-wide effects were estimated using a meta-analysis method.
Results: In total, 1692 patients from 6 institutions submitted 7823 eSyM assessments during the 16 weeks surrounding the recall period change. Shortening the recall period was associated with lower odds of severe symptom reporting in the surgery cohort (odds ratio = 0.65, 95% confidence interval = 0.46 to 0.93; P = .02) and lower odds of moderate and severe symptom reporting in the chemotherapy cohort (odds ratio = 0.83, 95% confidence interval = 0.71 to 0.97; P = .02). Among the most prevalent symptoms, 24-hour recall was associated with a lower rate of reporting postoperative constipation but no differences in reporting rates for other symptoms.
Conclusion: A shorter recall period was associated with a reduction in the proportion of patients reporting moderate-severe symptoms. The optimal recall period may vary depending on whether electronic patient-reported outcomes are collected for active symptom management, as a clinical trial endpoint, or another purpose. ClinicalTrials.gov ID NCT03850912.
背景:在常规肿瘤治疗中采用电子患者报告结果(ePRO)来管理症状的最佳方法仍不确定。eSyM 症状管理计划要求化疗和手术患者定期自我报告 12 种症状。根据护士和患者的反馈意见,将回忆时间从过去 7 天改为过去 24 小时:我们利用回忆期改变前后 16 周内提交的调查问卷,评估了所有 12 种症状中报告严重或中度严重症状的可能性,并分别评估了 5 种最常见症状的报告可能性。间断时间序列分析使用广义线性混合效应模型对变化的影响进行建模。手术组和化疗组分别进行分析。使用荟萃分析方法估算了整个研究的效果:在召回期变化前后的 16 周内,共有来自 6 家机构的 1,692 名患者提交了 7,823 次 eSyM 评估。缩短召回期与手术队列中严重症状报告几率降低(OR 0.65; 95% CI 0.46 to 0.93; p = .02)和化疗队列中中度严重症状报告几率降低(OR 0.83, 95% CI 0.71 to 0.97; p = .02)有关。在最常见的症状中,24 小时召回与较低的术后便秘报告率有关,但其他症状的报告率没有差异:结论:召回时间越短,报告中度-重度症状的患者比例越低。根据收集 ePRO 是为了进行积极的症状管理、作为临床试验终点还是其他目的,最佳召回期可能会有所不同。(Clinicaltrails.gov (NCT03850912)。
{"title":"Effects of a change in recall period on reporting severe symptoms: an analysis of a pragmatic multisite trial.","authors":"Roshan Paudel, Andrea C Enzinger, Hajime Uno, Christine Cronin, Sandra L Wong, Don S Dizon, Hannah Hazard Jenkins, Jessica Bian, Raymond U Osarogiagbon, Roxanne E Jensen, Sandra A Mitchell, Deborah Schrag, Michael J Hassett","doi":"10.1093/jnci/djae049","DOIUrl":"10.1093/jnci/djae049","url":null,"abstract":"<p><strong>Background: </strong>Optimal methods for deploying electronic patient-reported outcomes to manage symptoms in routine oncologic practice remain uncertain. The electronic symptom management (eSyM) program asks chemotherapy and surgery patients to self-report 12 common symptoms regularly. Feedback from nurses and patients led to changing the recall period from the past 7 days to the past 24 hours.</p><p><strong>Methods: </strong>Using questionnaires submitted during the 16 weeks surrounding the recall period change, we assessed the likelihood of reporting severe or moderate and severe symptoms across 12 common symptoms and separately for the 5 most prevalent symptoms. Interrupted time-series analyses modeled the effects of the change using generalized linear mixed-effects models. Surgery and chemotherapy cohorts were analyzed separately. Study-wide effects were estimated using a meta-analysis method.</p><p><strong>Results: </strong>In total, 1692 patients from 6 institutions submitted 7823 eSyM assessments during the 16 weeks surrounding the recall period change. Shortening the recall period was associated with lower odds of severe symptom reporting in the surgery cohort (odds ratio = 0.65, 95% confidence interval = 0.46 to 0.93; P = .02) and lower odds of moderate and severe symptom reporting in the chemotherapy cohort (odds ratio = 0.83, 95% confidence interval = 0.71 to 0.97; P = .02). Among the most prevalent symptoms, 24-hour recall was associated with a lower rate of reporting postoperative constipation but no differences in reporting rates for other symptoms.</p><p><strong>Conclusion: </strong>A shorter recall period was associated with a reduction in the proportion of patients reporting moderate-severe symptoms. The optimal recall period may vary depending on whether electronic patient-reported outcomes are collected for active symptom management, as a clinical trial endpoint, or another purpose. ClinicalTrials.gov ID NCT03850912.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":null,"pages":null},"PeriodicalIF":9.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11223809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alaina M Bever, Dong Hang, Dong Hoon Lee, Fred K Tabung, Tomotaka Ugai, Shuji Ogino, Jeffrey A Meyerhardt, Andrew T Chan, A Heather Eliassen, Liming Liang, Meir J Stampfer, Mingyang Song
Background: Inflammation and metabolic dysregulation are associated with increased risk of colorectal cancer (CRC); the underlying mechanisms are not fully understood. We characterized metabolomic signatures of inflammation and metabolic dysregulation and evaluated the association of the signatures and individual metabolites with CRC risk.
Methods: Among 684 incident CRC cases and 684 age-matched controls in the Nurses' Health Study (n = 818 women) and Health Professionals Follow-up Study (n = 550 men), we applied reduced rank and elastic net regression to 277 metabolites for markers of inflammation (C-reactive protein, interleukin 6, tumor necrosis factor receptor superfamily member 1B, and growth differentiation factor 15) or metabolic dysregulation (body mass index, waist circumference, C-peptide, and adiponectin) to derive metabolomic signatures. We evaluated the association of the signatures and individual metabolites with CRC using multivariable conditional logistic regression. All statistical tests were 2-sided.
Results: We derived a signature of 100 metabolites that explained 24% of variation in markers of inflammation and a signature of 73 metabolites that explained 27% of variation in markers of metabolic dysregulation. Among men, both signatures were associated with CRC (odds ratio [OR] = 1.34, 95% confidence interval [CI] = 1.07 to 1.68 per 1-standard deviation increase, inflammation; OR = 1.25, 95% CI = 1.00 to 1.55 metabolic dysregulation); neither signature was associated with CRC in women. A total of 11 metabolites were individually associated with CRC and biomarkers of inflammation or metabolic dysregulation among either men or women.
Conclusion: We derived metabolomic signatures and identified individual metabolites associated with inflammation, metabolic dysregulation, and CRC, highlighting several metabolites as promising candidates involved in the inflammatory and metabolic dysregulation pathways for CRC incidence.
{"title":"Metabolomic signatures of inflammation and metabolic dysregulation in relation to colorectal cancer risk.","authors":"Alaina M Bever, Dong Hang, Dong Hoon Lee, Fred K Tabung, Tomotaka Ugai, Shuji Ogino, Jeffrey A Meyerhardt, Andrew T Chan, A Heather Eliassen, Liming Liang, Meir J Stampfer, Mingyang Song","doi":"10.1093/jnci/djae047","DOIUrl":"10.1093/jnci/djae047","url":null,"abstract":"<p><strong>Background: </strong>Inflammation and metabolic dysregulation are associated with increased risk of colorectal cancer (CRC); the underlying mechanisms are not fully understood. We characterized metabolomic signatures of inflammation and metabolic dysregulation and evaluated the association of the signatures and individual metabolites with CRC risk.</p><p><strong>Methods: </strong>Among 684 incident CRC cases and 684 age-matched controls in the Nurses' Health Study (n = 818 women) and Health Professionals Follow-up Study (n = 550 men), we applied reduced rank and elastic net regression to 277 metabolites for markers of inflammation (C-reactive protein, interleukin 6, tumor necrosis factor receptor superfamily member 1B, and growth differentiation factor 15) or metabolic dysregulation (body mass index, waist circumference, C-peptide, and adiponectin) to derive metabolomic signatures. We evaluated the association of the signatures and individual metabolites with CRC using multivariable conditional logistic regression. All statistical tests were 2-sided.</p><p><strong>Results: </strong>We derived a signature of 100 metabolites that explained 24% of variation in markers of inflammation and a signature of 73 metabolites that explained 27% of variation in markers of metabolic dysregulation. Among men, both signatures were associated with CRC (odds ratio [OR] = 1.34, 95% confidence interval [CI] = 1.07 to 1.68 per 1-standard deviation increase, inflammation; OR = 1.25, 95% CI = 1.00 to 1.55 metabolic dysregulation); neither signature was associated with CRC in women. A total of 11 metabolites were individually associated with CRC and biomarkers of inflammation or metabolic dysregulation among either men or women.</p><p><strong>Conclusion: </strong>We derived metabolomic signatures and identified individual metabolites associated with inflammation, metabolic dysregulation, and CRC, highlighting several metabolites as promising candidates involved in the inflammatory and metabolic dysregulation pathways for CRC incidence.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":null,"pages":null},"PeriodicalIF":9.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11223797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}