Evaluation of spatiotemporal heterogeneity of PDL1 expression in gastroesophageal adenocarcinoma (GEA) at baseline diagnosis and after chemotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4528-4528 ◽  
Author(s):  
Katherine I. Zhou ◽  
Bryan Peterson ◽  
Anthony Serritella ◽  
Natalie Reizine ◽  
Yan Wang ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Stage Iv ◽  
Predictive Marker ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Molecular Heterogeneity ◽  
Therapeutic Implications ◽  
Hazards Model ◽  
Before And After

4528 Background: PDL1 expression is a predictive marker for response to anti-PD1/PDL1 agents (IO) for GEA. As a prognostic biomarker, data are conflicting. Molecular heterogeneity of various biomarkers for GEA has been established. To characterize heterogeneity of PDL1 expression and its clinical relevance, we compared PDL1 expression in primary (10) and metastatic (met) tumors of newly diagnosed stage IV advanced GEA (aGEA), and before and after chemotherapy treatment (tx) for stage II–IV GEA. We assessed the prognostic relevance of PDL1 expression in aGEA. Methods: We retrospectively reviewed a cohort of 130 patients (pts) diagnosed with GEA in 2013–2019, with a total of 328 tumor samples with PDL1 expression data. PDL1 was defined as positive if combined positive score (CPS) was ≥1 using the 22C3 pharmDx assay. Analysis was performed by McNemar’s test for paired PDL1 and univariate Cox proportional-hazards model for overall survival (OS). Results: Of 328 tumors, 45% were PDL1+ and 55% PDL1-. CPS ranged 0–100 (median 1, IQR 0–5), and CPS was ≥10 for 19% of tumors. Concordance between PDL1 status of paired baseline 10 and baseline met tumors was 63% (32/51) (Table). Of 31 PDL1+ baseline 10 tumors, 52% (16/31) had PDL1- paired baseline met tumors, while of 20 PDL1- baseline 10 tumors, only 15% (3/20) had PDL1+ paired baseline met tumors. Only 35% (18/51) of met tumors were PDL1+, compared to 61% (31/51) PDL1+ 10 tumors ( p< 0.003). Post-tx tumors exhibited 62% (46/74) concordance of PDL1 status compared to pre-tx 10 tumors. Of 43 PDL1+ baseline tumors, 35% (15/43) were PDL1- post-tx; of 31 PDL1- baseline tumors, 42% (13/31) were PDL1+ post-tx ( p= 0.71). In pts with aGEA at diagnosis, OS did not significantly differ depending on baseline 10 tumor PDL1 status (median OS of 17.9 [95% CI 14.6–26.5] months for PDL1- and 16.7 [12.0–26.3] months for PDL1+; p= 0.6), nor depending on baseline met PDL1 status. Conclusions: PDL1 expression demonstrated notable baseline discordance between 10 and met tumors, particularly directional from PDL1+ 10 tumor to PDL1- met. Discordance before and after chemotherapy was also observed, but with similar proportions of PDL1+ pre-tx and post-tx tumors. These findings may have predictive IO therapeutic implications if confirmed in larger independent analyses. [Table: see text]

Evaluation of spatiotemporal heterogeneity of tumor mutational burden (TMB) in gastroesophageal adenocarcinoma (GEA) at baseline diagnosis and after chemotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4546-4546 ◽  
Author(s):  
Katherine I. Zhou ◽  
Bryan Peterson ◽  
Anthony Serritella ◽  
Natalie Reizine ◽  
Yan Wang ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Stage Iv ◽  
Predictive Marker ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Molecular Heterogeneity ◽  
Mutational Burden ◽  
Tumor Mutational Burden ◽  
Spatiotemporal Heterogeneity

4546 Background: Tumor mutational burden (TMB) may be a predictive marker for response to anti-PD1/PDL1 agents (IO). Molecular heterogeneity of various biomarkers for GEA has been established. To characterize heterogeneity of TMB and its clinical relevance, we compared TMB in primary (10) & metastatic (met) tumors at baseline newly diagnosed stage IV advanced GEA (aGEA), and before & after chemotherapy treatment (tx) for stage II–IV GEA. We assessed the prognostic relevance of TMB in aGEA. Methods: We retrospectively reviewed a cohort of 127 patients (pts) diagnosed with GEA in 2012–2019, for a total of 280 tumor samples with TMB data. TMB level was defined as low (≤5/Mb), intermediate (int) ( > 5/Mb, ≤15/Mb), or high (hi) (≥15/Mb), determined by Foundation One. Analysis was performed by Fisher’s exact test for PDL1/TMB, McNemar’s test for paired TMB, and univariate Cox proportional-hazards model for overall survival (OS). Results: Of 280 tumors, 50% (140/280) had low TMB, 45% (125/280) int TMB, & 5% (15/280) hi TMB. TMB ranged 0–58.6/Mb (median 5.3/Mb). Of tumors with hi TMB, 53% (8/15) were MSI-Hi, while of MSI-Hi tumors, 100% (8/8) were TMB hi. TMB level did not correlate with PDL1 status ( p= 0.83). Concordance between TMB levels of paired baseline 10 and baseline met tumors was 66% (29/44) (Table). TMB level was lower in the met than in the 10 in 23% (10/44) of cases, and higher in the met in 11% (5/44). Of 4 TMB hi baseline 10 tumors, 2 were not TMB hi in the met; of 40 TMB low/int baseline 10 tumors, 0 were TMB hi in the met ( p= 0.16). Post-tx tumors exhibited 71% (42/59) concordance of TMB levels compared to pre-tx 10 tumors. Of 2 TMB hi baseline tumors, 1 was not TMB hi in the post-tx tumor; of 57 TMB low/int baseline tumors, 0 were TMB hi in the post-tx tumor ( p= 0.32). In pts with aGEA at diagnosis, OS did not significantly differ depending on baseline 10 tumor TMB level (median OS of 21.4 [95% CI 15.4–27.9] months for TMB low, 14.6 [10.9–23.5] months for TMB int, and 9.6 [3.9–NA] for TMB hi; p= 0.3), nor depending on baseline met TMB level. Conclusions: Notable baseline spatial discordance of TMB was observed, particularly TMB hi 10 to low/int met. Discordance was also observed before & after tx, without significant increase towards TMB hi temporally. Spatiotemporal heterogeneity may impact the role of TMB as a predictive biomarker & warrants further study. [Table: see text]

scholarly journals Reductions in AFP and PIVKA-II can predict the efficiency of anti-PD-1 immunotherapy in HCC patients

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuqi Sun ◽  
Jie Mei ◽  
Wenping Lin ◽  
Ziliang Yang ◽  
Wei Peng ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Objective Response ◽  
Binary Logistic Regression ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Related Factors ◽  
Hazards Model ◽  
Before And After

Abstract Background Few biomarkers can predict the efficiency of PD-1 blockade in patients with hepatocellular carcinoma (HCC). This study aimed to investigate the prognostic role of AFP and PIVKA-II in HCC patients receiving anti-PD-1 immunotherapy. Methods A total of 235 HCC patients treated with PD-1 blockade were enrolled. Serum AFP and PIVKA-II levels were collected before and after treatments. The patients were divided into groups based on the reduction in AFP and PIVKA-II: AFP reduction ≤50% vs AFP reduction > 50% and PIVKA-II reduction ≤50% vs PIVKA-II reduction > 50%. The primary endpoints included objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Binary logistic regression analyses were used to explore the related factors of ORR. A Cox proportional hazards model was employed to identify the potential prognostic factors of PFS and OS. Results Among all the patients, 34.9% (82/235) achieved a complete or partial response. There was a positive correlation between AFP reduction > 50% or PIVKA-II reduction> 50% and the ORR of PD-1 blockade (P < 0.001 and = 0.003). PFS was significantly improved in patients with AFP reduction > 50% and PIVKA-II reduction > 50% (p < 0.001 and = 0.021). In addition, AFP reduction > 50% and PIVKA-II reduction> 50% were positively correlated with longer OS (p = 0.003 and 0.006). Conclusion Early reductions in AFP and PIVKA-II can be predictors of the efficacy of PD-1 blockade in HCC patients.

Expression of tryptophan metabolizing enzymes (TMEs) and its transporter, LAT1, in metastatic melanoma (MM): Prognostic and therapeutic implications.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e21014-e21014
Author(s):  
Dimitri G. Trembath ◽  
Paul B. Googe ◽  
Jill S. Frank ◽  
Madeline H Kowalski ◽  
Marcus Spearman ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Stage Iv ◽  
Tumor Infiltrating Lymphocytes ◽  
Melanoma Cells ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Therapeutic Implications ◽  
The Status

e21014 Background: The ECHO-301/KEYNOTE-252 trial failed to show clinical benefit of adding epacadostat to pembrolizumab in PD-1 inhibitor-naïve MM. We reasoned that the expression of other TMEs and/or LAT1 by melanoma cells plays a more important role. Methods: Melanoma tissues from stage III/IV pts were stained for the 4 TMEs (TPH1, TPH2, TDO2, IDO1) and LAT1 by single-color immunohistochemistry. Tissues were scored for the status of tumor-infiltrating lymphocytes (TILs) and the expression of 5 proteins separately in melanoma cells and TILs (if present). Association between protein expression, TIL status, and melanoma-specific overall survival was performed. Results: Tissues from 87 pts (stage IV, n = 25) were available. Expression of all 4 TMEs and LAT1 was significantly higher in melanoma cells compared to TILs ( p< 0.001); TPH1, TPH2, and TDO2 expression in melanoma cells was significantly higher than IDO1 (p < 0.001). Lower TPH1 expression in melanoma cells was associated with presence of TILs. Multivariate analysis using a Cox proportional hazards model that included expression of the 5 proteins in melanoma cells showed that high IDO1 was a favorable and high LAT1 expression was an adverse prognostic factor. Conclusions: Expression of TMEs and LAT1 by melanoma cells may have more important role in metastatic melanoma by depleting an essential amino acid from the tumor microenvironment. Pharmacologic targeting of TPH1/TPH2 (e.g. telotristat) may be more clinically relevant in MM as opposed to IDO1 inhibition.

scholarly journals Survival Benefit of Post-Operative Radiotherapy in Patients with Resectable Pancreatic Head Adenocarcinoma

2020 ◽  
Author(s):  
yu gan ◽  
su song ◽  
li bo ◽  
cheng fan
Keyword(s):  
Survival Benefit ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Pancreatic Head ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Beneficial Effects ◽  
Hazards Model ◽  
Before And After

Abstract Background Controversy still exis ts with regard to the beneficial effects of adjuvant radiotherapy (RT) on patients with resectable pancreatic head adenocarcinoma. The aim was to investigate the role of post-operative RT in resectable pancreatic head adenocarcinoma.Methods A total of 2092 patients with resectable pancreatic head adenocarcinoma were enrolled from 2004 to 2016. The data of these patients were obtained from the Surveillance, Epidemiology and End Results (SEER) database of the National Cancer Institute. The propensity score matching method was used to avoid selection bias of the treatment. A multivariable Cox proportional hazards model was used in analyzing the survival benefit from the utilization of post-operative RT.Results In total, 186 patients received post-operative RT after pancreatic head adenocarcinoma resection. Compared with patients who only underwent surgery (n = 1906), the subjects who had postoperative RT were younger (P = 0.000) and had a greater TNM stage (P = 0.00). The baseline characteristics of the two groups were well matched, and more notable in the clinicopathologic and demographic aspects. Before and after matching, the patients who received post-operative RT after pancreatic head adenocarcinoma resection had a higher survival rate than those who underwent only resection (P = 0.00). Subgroups analyses revealed that this benefit was restricted to patients with Lymph node invasion (P = 0.00).Conclusions Pancreatic head adenocarcinoma resection followed by post-operative RT demonstrated considerable survival benefit in relation to surgery alone.

Expression of breast cancer resistance protein (BCRP) in esophageal cancers (EC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13529-e13529
Author(s):  
A. Bharthuar ◽  
T. Khoury ◽  
K. N. Haas ◽  
T. Mashtare ◽  
J. Black ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Stage Iv ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Esophageal Mucosa ◽  
Cancer Resistance ◽  
Exact Test ◽  
Hazards Model ◽  
Stage 1

e13529 Background: EC patients face a dismal outcome despite tri-modality management strategy. Median survival remains 15–18 months despite platinum, fluropyrimidine & irinotecan based therapy. BCRP is an ATP-dependent efflux protein associated with chemotherapy (CT) (e.g. irinotecan) resistance. Role of BCRP expression in EC and normal esophageal cells is not known. We examined the expression of this protein and correlate it with survival (OS) in patients receiving irinotecan-based CT. Methods: With IRB approval, 40 cases of EC diagnosed between 2004 and 2008 were stained for BCRP expression by IHC & scored by the pathologist blinded to clinical data. Baseline demographics, therapy given & OS data were collected and correlated with BCRP expression. BCRP score (membrane or cytoplasm) >/= 30 was considered positive (calculated by multiplying BCRP intensity and % staining). Fisher's exact test used to determine association between BCRP expression & demographics. Cox proportional hazards model used for association of BCRP & OS. Results: Baseline patient and tumor characteristics: Gender: M 35, F 5; Histology: 37 Adenoca & 3 SCC; Stage 1-III 27, Stage IV 10, unknown 3; CT: cisplatin+irinotecan (n=16), oxaliplatin+fluoropyrimidine (n=8), other (n=16); IHC: 30 of 40 cancers (75%) expressed BCRP [strong (n=28) & intermediate (n=3); membranous (n=17), cytoplasmic (n=27) & both (n=14)]. Down-regulation of BCRP expression in tumor compared to normal cells seen in 40% of patients. Median OS was 19 months with no difference in OS between BCRP positive and negative patients (p=0.13). Estimated hazard ratio (HR) of death for BCRP positive patients was 2.29 (95% CI 0.79 - 6.64).There was no association between BCRP expression and stage, age, gender or histology. For patients who received cisplatin and irinotecan as first line CT there was no difference in OS (p=0.39) of BCRP negative versus positive patients. Conclusions: BCRP expression is seen in a majority of EC & normal esophageal mucosa. Response rates to irinotecan based therapies are seen in 30–40 % of EC, whether the 40% with low tumor BCRP constitute a majority of the responders needs to be prospectively validated in a larger dataset & should include markers that predict response to 5-FU & platinum based CT to allow individualizing therapy for this cancer. No significant financial relationships to disclose.

scholarly journals Risk factors associated with major adverse cardiac and cerebrovascular events following percutaneous coronary intervention: a 10-year follow-up comparing random survival forest and Cox proportional-hazards model

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Maryam Farhadian ◽  
Sahar Dehdar Karsidani ◽  
Azadeh Mozayanimonfared ◽  
Hossein Mahjub
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Coronary Intervention ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
Cerebrovascular Events ◽  
Long Term Follow Up ◽  
Stent Length

Abstract Background Due to the limited number of studies with long term follow-up of patients undergoing Percutaneous Coronary Intervention (PCI), we investigated the occurrence of Major Adverse Cardiac and Cerebrovascular Events (MACCE) during 10 years of follow-up after coronary angioplasty using Random Survival Forest (RSF) and Cox proportional hazards models. Methods The current retrospective cohort study was performed on 220 patients (69 women and 151 men) undergoing coronary angioplasty from March 2009 to March 2012 in Farchshian Medical Center in Hamadan city, Iran. Survival time (month) as the response variable was considered from the date of angioplasty to the main endpoint or the end of the follow-up period (September 2019). To identify the factors influencing the occurrence of MACCE, the performance of Cox and RSF models were investigated in terms of C index, Integrated Brier Score (IBS) and prediction error criteria. Results Ninety-six patients (43.7%) experienced MACCE by the end of the follow-up period, and the median survival time was estimated to be 98 months. Survival decreased from 99% during the first year to 39% at 10 years' follow-up. By applying the Cox model, the predictors were identified as follows: age (HR = 1.03, 95% CI 1.01–1.05), diabetes (HR = 2.17, 95% CI 1.29–3.66), smoking (HR = 2.41, 95% CI 1.46–3.98), and stent length (HR = 1.74, 95% CI 1.11–2.75). The predictive performance was slightly better by the RSF model (IBS of 0.124 vs. 0.135, C index of 0.648 vs. 0.626 and out-of-bag error rate of 0.352 vs. 0.374 for RSF). In addition to age, diabetes, smoking, and stent length, RSF also included coronary artery disease (acute or chronic) and hyperlipidemia as the most important variables. Conclusion Machine-learning prediction models such as RSF showed better performance than the Cox proportional hazards model for the prediction of MACCE during long-term follow-up after PCI.

scholarly journals Elevated plasma growth and differentiation factor 15 predicts incident anemia in older adults aged 60 years and older

2020 ◽  
Author(s):  
Yuko Yamaguchi ◽  
Marta Zampino ◽  
Toshiko Tanaka ◽  
Stefania Bandinelli ◽  
Yusuke Osawa ◽  
...  
Keyword(s):  
Older Adults ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Differentiation Factor ◽  
Hazards Model ◽  
Increased Risk ◽  
The Relationship

Abstract Background Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts the development of anemia. Methods We examined the relationship between plasma GDF-15 concentrations at baseline in 708 non-anemic adults, aged 60 years and older, with incident anemia during 15 years of follow-up among participants in the Invecchiare in Chianti (InCHIANTI) Study. Results During follow-up, 179 (25.3%) participants developed anemia. The proportion of participants who developed anemia from the lowest to highest quartile of plasma GDF-15 was 12.9%, 20.1%, 21.2%, and 45.8%, respectively. Adults in the highest quartile of plasma GDF-15 had an increased risk of developing anemia (Hazards Ratio 1.15, 95% Confidence Interval 1.09, 1.21, P&lt;.0001) compared to those in the lower three quartiles in a multivariable Cox proportional hazards model adjusting for age, sex, serum iron, soluble transferrin receptor, ferritin, vitamin B12, congestive heart failure, diabetes mellitus, and cancer. Conclusions Circulating GDF-15 is an independent predictor for the development of anemia in older adults.

scholarly journals Dementia Adjudication Triggers Associated With Increased Mortality for Older Australians: Evidence From ASPREE

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 161-161
Author(s):  
Jane Banaszak-Holl ◽  
Xiaoping Lin ◽  
Jing Xie ◽  
Stephanie Ward ◽  
Henry Brodaty ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
The Elderly ◽  
Cox Proportional Hazards ◽  
Service Planning ◽  
Cox Proportional Hazards Model ◽  
Cognitive Test ◽  
Risk Of Death ◽  
Hazards Model ◽  
Using Data

Abstract Research Aims: This study seeks to understand whether those with dementia experience higher risk of death, using data from the ASPREE (ASPirin in Reducing Events in the Elderly) clinical trial study. Methods: ASPREE was a primary intervention trial of low-dose aspirin among healthy older people. The Australian cohort included 16,703 dementia-free participants aged 70 years and over at enrolment. Participants were triggered for dementia adjudication if cognitive test results were poorer than expected, self-reporting dementia diagnosis or memory problems, or dementia medications were detected. Incidental dementia was adjudicated by an international adjudication committee using the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV) criteria and results of a neuropsychological battery and functional measures with medical record substantiation. Statistical analyses used a cox proportional hazards model. Results: As previously reported, 1052 participants (5.5%) died during a median of 4.7 years of follow-up and 964 participants had a dementia trigger, of whom, 575 (60%) were adjucated as having dementia. Preliminary analyses has shown that the mortality rate was higher among participants with a dementia trigger, regardless of dementia adjudication outcome, than those without (15% vs 5%, Χ2 = 205, p &lt;.001). Conclusion: This study will provide important analyses of differences in the hazard ratio for mortality and causes of death among people with and without cognitive impairment and has important implications on service planning.

scholarly journals Evaluation of Changes on World Stock Exchanges in Connection with the SARS-CoV-2 Pandemic. Survival Analysis Methods

Risks ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 121
Author(s):  
Beata Bieszk-Stolorz ◽  
Krzysztof Dmytrów
Keyword(s):  
Survival Analysis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Stock Exchange ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Stock Exchanges ◽  
Analysis Methods ◽  
Hazards Model ◽  
Kaplan Meier

The aim of our research was to compare the intensity of decline and then increase in the value of basic stock indices during the SARS-CoV-2 coronavirus pandemic in 2020. The survival analysis methods used to assess the risk of decline and chance of rise of the indices were: Kaplan–Meier estimator, logit model, and the Cox proportional hazards model. We observed the highest intensity of decline in the European stock exchanges, followed by the American and Asian plus Australian ones (after the fourth and eighth week since the peak). The highest risk of decline was in America, then in Europe, followed by Asia and Australia. The lowest risk was in Africa. The intensity of increase was the highest in the fourth and eleventh week since the minimal value had been reached. The highest odds of increase were in the American stock exchanges, followed by the European and Asian (including Australia and Oceania), and the lowest in the African ones. The odds and intensity of increase in the stock exchange indices varied from continent to continent. The increase was faster than the initial decline.

scholarly journals Association between milk and yogurt intake and mortality: a community-based cohort study (Yamagata study)

BMC Nutrition ◽  
2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Akiko Nakanishi ◽  
Erika Homma ◽  
Tsukasa Osaki ◽  
Ri Sho ◽  
Masayoshi Souri ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Hazard Analysis ◽  
Total Mortality ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Milk Intake ◽  
Community Based ◽  
Hazards Model ◽  
Kaplan Meier

Abstract Background Dairy products are known as health-promoting foods. This study prospectively examined the association between milk and yogurt intake and mortality in a community-based population. Methods The study population comprised of 14,264 subjects aged 40–74 years who participated in an annual health checkup. The frequency of yogurt and milk intake was categorized as none (< 1/month), low (< 1/week), moderate (1–6/week), and high (> 1/day) intake. The association between yogurt and milk intake and total, cardiovascular, and cancer-related mortalities was determined using the Cox proportional hazards model. Results During the follow-up period, there were 265 total deaths, 40 cardiovascular deaths and 90 cancer-related deaths. Kaplan–Meier analysis showed that the total mortality in high/moderate/low yogurt intake and moderate/low milk intake groups was lower than that in none group (log-rank, P < 0.01). In the multivariate Cox proportional hazard analysis adjusted for possible confounders, the hazard ratio (HR) for total mortality significantly decreased in high/moderate yogurt intake group (HR: 0.62, 95% confidence interval [CI]: 0.42–0.91 for high intake, HR: 0.70, 95%CI: 0.49–0.99 for moderate intake) and moderate milk intake group (HR: 0.67, 95% CI: 0.46–0.97) compared with the none yogurt and milk intake groups. A similar association was observed for cancer-related mortality, but not for cardiovascular mortality. Conclusions Our study showed that yogurt and milk intake was independently associated with a decrease in total and cancer-related mortalities in the Japanese population.

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