Risk Of Cancer-specific Mortality Research Articles

Recommendations for broadening eligibility criteria in esophagus cancer clinical trials: the mortality disparity of esophagus cancer as a first or second primary malignancy.

Esophagus cancer as a second primary malignancy (esophagus-2) is increasingly common, but its prognosis is poorly understood. This study aims to examine the overall, non-cancer related and cancer-specific survival of patients diagnosed with esophagus-2 compared to the first primary esophagus cancer (esophagus-1). We included primary esophagus cancer patients diagnosed from 1975 to 2019 in the Surveillance, Epidemiology, and End Results program. Esophagus-2 was identified in patients with a previous diagnosis of non-esophageal primary malignancy. Hazard ratios of overall, esophagus cancer-specific and non-cancer related mortality were estimated among patients with esophagus-2 compared to esophagus-1, adjusting for age, gender, tumor stage and other demographic and clinical characteristics. A total of 74,521 and 14,820 patients were identified as esophagus-1 and esophagus-2 respectively. Esophagus-2 patients suffered lower risk of esophagus cancer-specific mortality in initial 5 years but with similar risk thereafter, independent of tumor characteristics and treatment. In the first 5 years after diagnosis, patients with esophagus-2 had similar risk of overall mortality with those with esophagus-1 but increased risk thereafter. As for non-cancer related mortality, esophagus-2 patients had higher risk all along. Esophagus-2 patients should not be entirely excluded from clinical trial and a 3-year exclusion window is suggested. A conservative approach to manage esophagus-2 solely based on malignancy history is not supported but effort should be put into surveillance, prevention and management of the comorbidities and complications for the first malignancy.

Association of depressive symptoms and sleep disturbances with survival among US adult cancer survivors

BackgroundDepression and sleep disturbances are associated with increased risks of various diseases and mortality, but their impacts on mortality in cancer survivors remain unclear. The objective of this study was to characterize the independent and joint associations of depressive symptoms and sleep disturbances with mortality outcomes in cancer survivors.MethodsThis population-based prospective cohort study included cancer survivors aged ≥ 20 years (n = 2947; weighted population, 21,003,811) from the National Health and Nutrition Examination Survey (NHANES) 2007–2018 cycles. Depressive symptoms and sleep disturbances were self-reported. Depressive symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9). Death outcomes were determined by correlation with National Death Index records through December 31, 2019. Primary outcomes included all-cause, cancer-specific, and noncancer mortality.ResultsDuring the median follow-up of 69 months (interquartile range, 37–109 months), 686 deaths occurred: 240 participants died from cancer, 146 from heart disease, and 300 from other causes. Separate analyses revealed that compared with a PHQ-9 score (0–4), a PHQ-9 score (5–9) was associated with a greater risk of all-cause mortality (hazard ratio [HR], 1.28; 95% CI, 1.03–1.59), and a PHQ-9 score (≥ 10) was associated with greater risk of all-cause mortality (HR, 1.37; 95% CI, 1.04–1.80) and noncancer mortality (HR, 1.45; 95% CI, 1.01–2.10). Single sleep disturbances were not associated with mortality risk. In joint analyses, the combination of a PHQ-9 score ≥ 5 and no sleep disturbances, but not sleep disturbances, was associated with increased risks of all-cause mortality, cancer-specific mortality, and noncancer mortality. Specifically, compared with individuals with a PHQ-9 score of 0–4 and no sleep disturbances, HRs for all-cause mortality and noncancer mortality in individuals with a PHQ-9 score of 5–9 and no sleep disturbances were 1.72 (1.21–2.44) and 1.69 (1.10–2.61), respectively, and 2.61 (1.43–4.78) and 2.77 (1.27–6.07), respectively, in individuals with a PHQ-9 score ≥ 10 and no sleep disturbances; HRs for cancer-specific mortality in individuals with a PHQ-9 score ≥ 5 and no sleep disturbances were 1.95 (1.16–3.27).ConclusionsDepressive symptoms were linked to a high risk of mortality in cancer survivors. The combination of a PHQ-9 score (≥ 5) and an absence of self-perceived sleep disturbances was associated with greater all-cause mortality, cancer-specific mortality, and noncancer mortality risks, particularly in individuals with a PHQ-9 score (≥ 10).

Low Expression of GRIM-19 Correlates with Poor Prognosis in Patients with Upper Urinary Tract Urothelial Carcinoma

Purpose: This study aimed to clarify the expression of a gene associated with Retinoid- Interferon-Induced Mortality-19 (GRIM-19) in Upper Urinary Tract Urothelial Carcinoma (UUTUC) and its prognostic significance for UUTUC patients. Materials and Methods: Immunohistochemical (IHC) staining was used to determine the GRIM-19 expression in 70 paired samples. Progression-Free Survival (PFS) and Cancer-Specific Survival (CSS) were assessed using the Kaplan-Meier method. The independent prognostic factors for PFS and CSS were analyzed by multivariable Cox regression models. Results: IHC staining showed that GRIM-19 expression was significantly decreased in UUTUC, and its cellular location changed from being both cytoplasmic and nuclear to only cytoplasmic. Kaplan- Meier analysis revealed that the patients with tumors expressing low GRIM-19 had a significantly higher risk for tumor progression (P = 0.002) and cancer-specific mortality (P < 0.001) compared to those with high GRIM-19 levels. The Cox regression showed that both GRIM-19 expression (P = 0.025) and lymph node metastasis (LN) (P = 0.007) were independent predictors of progression in the muscle-invasive (MIC) subgroup. GRIM-19 expressions (entire cohort: P = 0.011; MIC subgroup: P = 0.025), LN (entire cohort: P = 0.019; MIC subgroup: P = 0.007), and progression (entire cohort: P < 0.001; MIC subgroup: P < 0.001) were independent predictors of cancer-specific survival. Conclusion: Low expression of GRIM-19 in patients with UUTUC had significantly shorter PFS or CSS compared to those with high GRIM-19-expressing tumors. High GRIM-19 expression was also strongly associated with longer PFS in MIC patients. It indicates that GRIM-19 might serve as a promising prognostic biomarker for UUTUC patients.

Constructing a prognostic model for colorectal cancer with synchronous liver metastases after preoperative chemotherapy: a study based on SEER and an external validation cohort.

The combination of preoperative chemotherapy and surgical treatment has been shown to significantly enhance the prognosis of colorectal cancer with liver metastases (CRLM) patients. Nevertheless, as a result of variations in clinicopathological parameters, the prognosis of this particular group of patients differs considerably. This study aimed to develop and evaluate Cox proportional risk regression model and competing risk regression model using two patient cohorts. The goal was to provide a more precise and personalized prognostic evaluation system. We collected information on individuals who had a pathological diagnosis of colorectal cancer between 2000 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) Database. We obtained data from patients who underwent pathological diagnosis of colorectal cancer and got comprehensive therapy at the hospital between January 1, 2010, and June 1, 2022. The SEER data collected after screening according to the inclusion and exclusion criteria were separated into two cohorts: a training cohort (training cohort) and an internal validation cohort (internal validation cohort), using a random 1:1 split. Subgroup Kaplan-Meier (K-M) survival analyses were conducted on each of the three groups. The data that received following screening from the hospital were designated as the external validation cohort. The subsequent variables were chosen for additional examination: age, gender, marital status, race, tumor site, pretreatment carcinoembryonic antigen level, tumor size, T stage, N stage, pathological grade, number of tumor deposits, perineural invasion, number of regional lymph nodes examined, and number of positive regional lymph nodes. The primary endpoint was median overall survival (mOS). In the training cohort, we conducted univariate Cox regression analysis and utilized a stepwise regression approach, employing the Akaike information criterion (AIC) to select variables and create Cox proportional risk regression models. We evaluated the accuracy of the model using calibration curve, receiver operating characteristic curve (ROC), and area under curve (AUC). The effectiveness of the models was assessed using decision curve analysis (DCA). To evaluate the non-cancer-related outcomes, we analyzed variables that had significant impacts using subgroup cumulative incidence function (CIF) and Gray's test. These analyses were used to create competing risk regression models. Nomograms of the two models were constructed separately and prognostic predictions were made for the same patients in SEER database. This study comprised a total of 735 individuals. The mOS of the training cohort, internal validation cohort, and QDU cohort was 55.00months (95%CI 46.97-63.03), 48.00months (95%CI 40.65-55.35), and 68.00months (95%CI 54.91-81.08), respectively. The multivariate Cox regression analysis revealed that age, N stage, presence of perineural infiltration, number of tumor deposits and number of positive regional lymph nodes were identified as independent prognostic risk variables (p < 0.05). In comparison to the conventional TNM staging model, the Cox proportional risk regression model exhibited a higher C-index. After controlling for competing risk events, age, N stage, presence of perineural infiltration, number of tumor deposits, number of regional lymph nodes examined, and number of positive regional lymph nodes were independent predictors of the risk of cancer-specific mortality (p < 0.05). We have developed a prognostic model to predict the survival of patients with synchronous CRLM who undergo preoperative chemotherapy and surgery. This model has been tested internally and externally, confirming its accuracy and reliability.

Physical activity attenuates the excess mortality risk from prolonged sitting time among adults with osteoporosis or osteopenia.

Osteoporosis is a common generalized skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. This study aims to crystallize associations of physical activity (PA) and sedentary behaviour with the survival of adults with osteoporosis or osteopenia. A total of 3103 participants aged 50 years or older from the National Health and Nutrition Examination Survey (NHANES) were included in the study. All participants were diagnosed with osteopenia or osteoporosis. Multivariable Cox proportional hazards regression models were used to assess the association of PA and sedentary behaviour with overall mortality, cancer-related mortality, and cardiovascular disease (CVD)-related mortality. During 21349 person-years of follow-up, 675 deaths were documented. Highly active participants had a lower risk of all-cause (hazard ratios [HR] = 0.61; 95% confidence interval [CI], 0.42-0.87; P for trend = 0.004), cancer-specific (HR = 0.64; 95%CI, 0.35-1.17; P for trend = 0.132), CVD-specific (HR = 0.75; 95%CI, 0.45-1.25; P for trend = 0.452), and other (HR, 0.51; 95%CI, 0.29-0.88; P for trend = 0.005) mortality than inactive participants. And sitting time was not associated with mortality among physically active participants; while among those who were insufficiently active or inactive, longer sitting time was associated with increased risks of all-cause (HR per 1-h increase = 1.05; 95% CI, 1.01-1.09), cancer-specific (HR per 1 h increase = 0.98; 95% CI, 0.90-1.07), CVD-specific (HR per 1-h increase = 1.11; 95% CI = 1.04-1.18), and other (HR per 1-h increase = 1.05; 95% CI, 0.98-1.13) mortality in a dose-response manner. PA can attenuate the excess mortality risk from prolonged sitting for individuals with osteoporosis and/or osteopenia. The combination of prolonged sedentary behaviour with inactive (participants without any PA during a week) PA was associated with an increased risk of mortality. The all-cause mortality risk of individuals who engage in less than 150 min/wk PA and sit more than 8 h/d is 2.02 (95% CI, 1.37-2.99) times higher than that of individuals who engage in more than 150 min/wk PA and sit less than 4 h/d.

Statin use and risks of breast cancer recurrence and mortality.

Preclinical evidence suggests improved breast cancer survival associated with statin use, but findings from observational studies are conflicting and remain inconclusive. The objective of this study was to assess the association between statin use after cancer diagnosis and cancer outcomes among breast cancer patients. In this retrospective cohort study, 38,858 women aged ≥66 years who were diagnosed with localized and regional stage breast cancer from 2008 through 2017 were identified from the linked Surveillance, Epidemiology, and End Results Medicare database. Statin use was ascertained from Medicare Part D pharmacy claims data. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between post-diagnosis statin use and risks of breast cancer recurrence and breast cancer-specific mortality. Over a median follow-up of 2.9 years for recurrence and 3.7 years for mortality, 1446 women experienced a recurrence, and 2215 died from breast cancer. The mean duration of post-diagnosis statin use was 2.2 years. Statin use post-diagnosis was not associated with recurrence risk (HR, 1.05; 95% CI, 0.91-1.21), but was associated with a reduced risk of cancer-specific mortality (HR, 0.85; 95% CI, 0.75-0.96). The reduction was more pronounced in women with hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer (HR, 0.71; 95% CI, 0.57-0.88). These findings suggest that post-diagnosis statin use is associated with improved cancer-specific survival in women with breast cancer and should be confirmed in randomized trials of statin therapy in breast cancer patients.

Survival benefit of radical prostatectomy in patients with advanced TURP-diagnosed prostate cancer: a population-based real-world study

ObjectivesA considerable number of patients are diagnosed with prostate cancer (PCa) by transurethral resection of the prostate (TURP). We aimed to evaluate whether radical prostatectomy (RP) brings survival benefits for these patients, especially in the elderly with advanced PCa.Patients and methodsWe used the Surveillance, Epidemiology, and End Results (SEER) database to obtain PCa cases diagnosed with TURP. After the propensity matching score (PSM) for case matching, univariate, multivariate, and subgroup analyses were performed to investigate whether RP impacts the survival benefit.Results4,677 cases diagnosed with PCa by TURP from 2010 to 2019 were obtained, including 1,313 RP patients and 3,364 patients with no RP (nRP). 9.6% of RP patients had advanced PCa. With or without PSM, cancer-specific mortality (CSM) and overall mortality (OM) were significantly reduced in the RP patients compared to the nRP patients, even for older (> 75 ys.) patients with advanced stages (all p < 0.05). Except for RP, younger age (≤ 75 ys.), being married, and earlier stage (localized) contributed to a significant reduction of CSM risk (all p < 0.05). These survival benefits had no significant differences among patients of different ages, married or single, and at different stages (all p for interaction > 0.05).ConclusionsBased on this retrospective population-matched study, we first found that in patients diagnosed with PCa by TURP, RP treatment may lead to a survival benefit, especially a reduction in CSM, even in old aged patients (> 75 ys.) with advanced PCa.

Abstract PO1-11-05: Diet quality and cardiovascular disease risk among breast cancer survivors in the Pathways Study

Abstract Background: While studies have shown that breast cancer survivors with healthier diets have a lower risk of non-breast cancer-specific and all-cause mortality after a breast cancer diagnosis, the relationship between diet quality and cardiovascular disease (CVD) among breast cancer survivors is not well characterized. We examined the association between diet quality at the time of breast cancer diagnosis and CVD-related outcomes in the Pathways Study, a prospective cohort of 3,415 women diagnosed with invasive breast cancer. Methods: This analysis included four diet quality indices (DQIs) consistent with healthy eating: 1. Dietary Approaches to Stop Hypertension (DASH), 2. healthy plant-based dietary index (hPDI), 3. 2015 Healthy Eating Index (HEI), 4. American Cancer Society nutrition guidelines (ACS). Each DQI was calculated from food frequency questionnaires (FFQ) at or around the time of breast cancer diagnosis, between 2005 and 2013, with a higher score representing a more healthful dietary pattern. DQI scores were categorized into quartiles with the most concordant diets in the highest quartile and the least concordant diets in the lowest quartile, for each DQI. CVD outcomes were ascertained through December 31, 2021 and included ischemic heart disease, heart failure, cardiomyopathy, stroke/transient ischemic attack, arrhythmia, cardiac arrest, valvular disease, venous thromboembolic disease and CVD-related death. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated from proportional hazards regression accounting for clinical and demographic factors. Results: FFQs were completed an average 2.2 (range=0.3-7.6) months after a breast cancer diagnosis, and a total 623 (18.2%) incident CVD events and 340 (10.0%) CVD-related deaths were ascertained over 39,263 person-years of follow-up. Participants in the highest quartile of the DASH DQI had substantially reduced risks of heart failure (HR=0.50, 95% CI 0.31-0.81), arrhythmia (HR=0.76, 95% CI 0.62-0.93), cardiac arrest (HR=0.75, 95% CI 0.60-0.93), valvular disease (HR=0.77, 95% CI 0.62-0.96), venous thromboembolic disease (HR=0.74, 95% CI 0.59-0.92), and a 33% reduced risk of CVD-related death (HR=0.67, 95% CI 0.48-0.95) relative to those in the lowest quartile. Tests for trend across quartiles of the DASH DQI were also statistically significant at a p-value &amp;lt; 0.03. The only notable association found in the other three DQIs was between hPDI and lower risk of heart failure (HR=0.61, 95% CI 0.39-0.95) in women in the highest quartile compared to the lowest quartile (Table 1). Summary: These findings suggest that diets concordant with DASH and hPDI dietary patterns, may be beneficial for preventing CVD and CVD-related death after a breast cancer diagnosis. Table 1. Cox proportional hazard ratios and 95% confidence intervals for quartiles of diet quality indices and CVD events and CVD-related death Citation Format: Isaac Ergas, Janise Roh, Lawrence Kushi, Carlos Iribarren, Mai Nguyen-Huynh, Jamal Rana, Eileen Rillamas-Sun, Cecile Laurant, Valerie Lee, Richard Cheng, Heather Greenlee, Marilyn Kwan. Diet quality and cardiovascular disease risk among breast cancer survivors in the Pathways Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-11-05.

Abstract PO5-18-02: A Population-Based Analysis of the Impact of Omission of Anthracyclines in the Neoadjuvant Setting on the Risk of Mortality

Abstract Background Most patients with high-risk non-metastatic breast cancer are treated with neoadjuvant chemotherapy (NAC), which includes the administration of anthracyclines. The omission of anthracyclines was shown to be associated with excellent outcomes in selected patients. However, the extent to which anthracyclines are omitted among a population of women treated with NAC and its impact on mortality remain unclear. Objective To investigate the extent to which anthracyclines are omitted among a population of patients with invasive breast cancer treated with NAC and to examine the impact of non-anthracycline NAC on risks of breast cancer-specific and all-cause mortality. Methods We performed a retrospective population-based cohort analysis using patient-level health administrative data. The cohort includes women aged ≥18 years with stage I – III invasive breast cancer diagnosed between January 2012 and December 2020, treated with NAC and surgery. Patients were excluded if they received &amp;lt; 50% of the planned chemotherapy regimen, had bilateral breast cancer and/or a previous malignancy. The exposure of interest was anthracycline versus non-anthracycline NAC regimen. The primary and secondary endpoints were breast cancer-specific mortality and overall (all-cause) mortality. Multivariable Cox proportional hazards models adjusted by propensity score, and clinical/pathologic variables including a measure of comorbidity was performed to examine impact of omission of anthracyclines on outcomes. Cumulative incidence curves were generated to calculate the 5-year cumulative incidence of breast cancer and all-cause mortality for the whole cohort and in subset analyses, stratified by stage and receptor subtype. Results The cohort includes 4,180 women. Median follow was 62 months (IQR 44-85) and median age was 51 years (IQR 43-60). Most patients had low co-morbidities (96.0%), Stage II (44.1%) or Stage III (47.7%) disease, underwent mastectomy (72.6%), had axillary node dissection (64.4%) and received post-operative radiotherapy (88.8%). 279 (6.7%) individuals were treated with a non-anthracycline NAC and 3,901 (93.3 %) received an anthracycline NAC. Women who received non-anthracycline NAC were older (median 62 years vs. 50 years; p&amp;lt; 0.001), more likely to have stage I-II disease (77.0% vs. 51.3%; p&amp;lt; 0.001), and more likely to have triple-negative breast cancer (TNBC) (14.0% vs. 24.4%; p&amp;lt; 0.001) than those who received anthracyclines.On propensity adjusted multivariable analysis, factors associated with an increased risk of BC mortality include Stage III (HR 9.3, 95%CI 4.5 - 19.2, p&amp;lt; 0.0001) or stage II at presentation (HR 2.57 95% CI 1.24, 5.34, p=.01) (ref: stage I) or triple negative subtype (HR 3.7 95% CI 3.03, 4.51, p&amp;lt; .0001) (ref: hormone positive/HER2-). There was no significant difference in the relative risks of BC death (HR 0.8, 95% CI 0.5-1.27) or all-cause mortality (HR 0.85, 95% CI 0.60-1.21) for patients selected for treatment without anthracyclines compared to those treated with anthracyclines.Overall, among individuals selected for treatment without or with anthracycline NAC there was no significant difference in the 5-year cumulative incidence of BC (15.4% vs 10.5%, P=.05) or all-cause mortality (16.4% vs 11.9%, P=.07). However, the 5-year cumulative incidence of BC specific death (31.8% vs 16.5%, p=.03) and 5-year cumulative incidence of all-cause death (31.8% vs. 18.2%, p=.06) was higher among 420 women with HER2+ Stage III breast cancer who received non-anthracycline versus anthracycline-based chemotherapy. No difference was observed for other subgroups. Conclusions The omission of anthracyclines in NAC for individuals with stage III HER2+ breast cancer was associated with higher cumulative risks of breast cancer and all-cause mortality but no difference was observed for other subgroups. Further research is warranted to better understand in whom anthracyclines can be safely omitted. Citation Format: Danilo Giffoni M. M. Mata, Rinku Sutradhar, Matthew Castelo, Lena Nguyen, Danielle Rodin, Ezra Hahn, Omolara Fatiregun, Cindy Fong, Sabina Trebinjac, Andrea Eisen, Lawrence Paszat, Katarzyna Jerzak, Eileen Rakovitch. A Population-Based Analysis of the Impact of Omission of Anthracyclines in the Neoadjuvant Setting on the Risk of Mortality [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-18-02.

Abstract PO1-08-05: Using the CTS5 Score to Predict Late Recurrence in Male and Female Estrogen Receptor-Positive Breast Cancer Patients: a SEER database analysis of 65,729 cases

Abstract Purpose: The Clinical Treatment Score post-5 years (CTS5) score is a prognostic prediction tool to predict the risk of late distant recurrence in postmenopausal women with estrogen receptor-positive (ER+) breast cancer. Here we aimed to evaluate the prediction role of CTS5 in male breast cancer patients using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: ER+ early male and female breast cancer patients from the SEER database 2010-2013 were included. Clinicopathological features and the CTS5 score between the gender groups were compared using chi-square test. Overall survival (OS) and breast cancer-specific survival (BCSS) were estimated by Kaplan-Meier plots and compared between the groups with Log-rank test and multivariate cox proportional hazard regression models was used to determine the relationship between the CTS5 score and breast cancer survival outcomes in different gender cohorts. Results: A total of 65,729 ER+ breast cancer patients were included in the study and 611 were men. Male breast cancer was more likely to be diagnosed later in life (&amp;gt;50 years old, 87.1% vs 73.6%, p &amp;lt; 0.001), with more aggressive biological features (grade Ⅱ 51.6% vs 47.2%, p &amp;lt; 0.001; grade Ⅲ 37.8% vs 28.3%, p &amp;lt; 0.001) , and higher tumor burden (stage Ⅱ 45.8% vs 32.9%, p &amp;lt; 0.001, stage Ⅲ 17.5% vs 10.5%, p &amp;lt; 0.001) when compared to female counterparts. More male patients were CTS5 intermediate- or high-risk than female patients (high 7.9% vs 6.3%, intermediate 41.1% vs 24.6%, low 51.1% vs 69.1%, p &amp;lt; 0.001). Patients were divided into 0-5 year and &amp;gt;5 year cohorts based on whether they had a BCSS event within 5 years. In the &amp;gt;5 year cohort, patients with CTS5 high- or intermediate- risk had worse survival outcomes compared with low-risk cases in male and postmenopausal female patients but not in premenopausal female patients. In the 0-5 year cohort, the CTS5 score was not predictive for disease recurrence in male or postmenopausal patients. Conclusion: Male breast cancer patients were more likely to have aggressive tumors and worse survival outcomes. The CTS5 score could be applied to predict breast cancer-specific mortality risk beyond 5 years in male ER+ breast cancer patients. Citation Format: Fenhua Wang, Fang Ren, Jian Qian, Yunxia Xu, Jiayi Wu, Yu Zong, Xidong Gu. Using the CTS5 Score to Predict Late Recurrence in Male and Female Estrogen Receptor-Positive Breast Cancer Patients: a SEER database analysis of 65,729 cases [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-08-05.

Plant-Based Diets and Disease Progression in Men With Prostate Cancer.

Plant-based diets are associated with many health and environmental benefits, including primary prevention of fatal prostate cancer, but less is known about postdiagnostic plant-based diet patterns in individuals with prostate cancer. To examine whether postdiagnostic plant-based dietary patterns are associated with risk of prostate cancer progression and prostate cancer-specific mortality. This longitudinal observational cohort study included men with biopsy-proven nonmetastatic prostate cancer (stage ≤T3a) from the diet and lifestyle substudy within the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) enrolled at 43 urology practices across the US from 1999 to 2018. Participants completed a comprehensive diet and lifestyle questionnaire (including a validated food frequency questionnaire [FFQ]) between 2004 and 2016. Data were analyzed from August 2022 to April 2023. Overall plant-based diet index (PDI) and healthful plant-based diet index (hPDI) scores were calculated from the FFQ. The primary outcome was prostate cancer progression (recurrence, secondary treatment, bone metastases, or prostate cancer-specific mortality). The secondary outcome was prostate cancer-specific mortality. Among 2062 participants (median [IQR] age, 65.0 [59.0-70.0] years), 61 (3%) identified as African American, 3 (<1%) identified as American Indian or Alaska Native, 9 (<1%) identified as Asian or Pacific Islander, 15 (1%) identified as Latino, and 1959 (95%) identified as White. Median (IQR) time from prostate cancer diagnosis to FFQ was 31.3 (15.9-62.0) months after diagnosis. During a median (IQR) follow-up of 6.5 (1.3-12.8) years after the FFQ, 190 progression events and 61 prostate cancer-specific mortality events were observed. Men scoring in the highest vs lowest quintile of PDI had a 47% lower risk of progression (HR, 0.53; 95% CI, 0.37-0.74; P for trend = .003). The hPDI was not associated with risk of progression overall. However, among 680 individuals with Gleason grade 7 or higher at diagnosis, the highest hPDI quintile was associated with a 55% lower risk of progression compared with the lowest hPDI quintile (HR 0.45; 95% CI, 0.25-0.81; P for trend = .01); no association was observed in individuals with Gleason grade less than 7. In this cohort study of 2062 men with prostate cancer, higher intake of plant foods after prostate cancer diagnosis was associated with lower risk of cancer progression. These findings suggest nutritional assessment and counseling may be recommended to patients with prostate cancer to help establish healthy dietary practices and support well-being and overall health.

Association of serum 25-hydroxy-vitamin D concentration and risk of mortality in cancer survivors in the United States

PurposeCancer survivors have a high risk of mortality, and vitamin D (VD) is associated with the risk of mortality. This study is aim to examine the impact of VD on mortality in cancer survivors.MethodsA prospective study was conducted using data from the National Health and Nutrition Examination Survey. Participants were obtained information on their baseline characteristics, dietary habits, comorbidities, lifestyle, and serum 25-hydroxy VD [25(OH)D] concentrations. The weighted Cox proportional hazard and competing risk regression models were used to estimate the hazard ratio and 95% confidence intervals (HR, 95% CI) of mortality for different serum 25(OH)D concentrations. Restricted cubic spline (RCS) curves were utilized to illustrate the dose–response relationship between serum 25(OH)D concentrations and mortality.ResultsThe study encompassed 2,495 participants with cancer diagnoses. Multivariate models indicated that, compared to serum 25(OH)D concentrations below 58.5 nmol/L, concentrations exceeding 81.6 nmol/L were associated with reduced HRs for all-cause mortality (HR = 0.70; 95% CI: 0.56–0.87), cardiovascular mortality (HR = 0.53; 95% CI: 0.32–0.86), and cancer-specific mortality (HR = 0.66; 95% CI: 0.45–0.99). RCS curves revealed “L-shaped” associations between serum 25(OH)D concentration and both all-cause and cancer-specific mortality, with threshold effects at 87.9 nmol/L and 84.6 nmol/L, respectively. Conversely, the relationship between serum 25(OH)D concentration and cardiovascular mortality exhibited a more linear pattern, with a threshold at 88.7 nmol/L. Subgroup analyses highlighted a gender-specific interaction that elevated serum 25(OH)D concentrations were significantly more protective against mortality in males than in females, especially regarding cancer-specific mortality (P-interaction = 0.009).ConclusionElevated serum 25(OH)D concentrations were correlated with decreased risks of all-cause, cardiovascular, and cancer-specific mortality in cancer survivors, with benefit thresholds at 87.9, 88.7, and 84.6 nmol/L, respectively. These findings suggested that cancer survivors might benefit from higher vitamin D recommendations than the general population.

Association of food insecurity with overall and disease-specific mortality among cancer survivors in the US.

To investigate the association of food insecurity with overall and disease-specific mortality among US cancer survivors. Data from the National Health and Nutrition Examination Survey (NHANES 1999-2018) were used to examine the impact of food insecurity on mortality risks among cancer survivors in the US. Study participants aged ≥ 20years who had a history of cancer and completed the Adult Food Security Survey Module were included. Mortality data [all-cause, cancer, and cardiovascular (CVD) specific] through December 31, 2019 were obtained through linkage to the National Death Index. Using multivariable Cox proportional hazard regression, hazard ratios of mortality based on food security status were estimated. Among 5032 cancer survivors (mean age 62.5years; 58.0% women; 86.2% non-Hispanic White), 596 (8.8%) reported food insecurity. Overall, 1913 deaths occurred (609 cancer deaths and 420 CVD deaths) during the median follow-up of 6.8years. After adjusting for age, food insecurity was associated with a higher risk of overall (HR = 1.93; 95% CI = 1.56-2.39), CVD-specific (HR = 1.95; 95% CI = 1.24-3.05), and cancer-specific (HR = 1.70; 95% CI = 1.20-2.42) mortality (P < 0.001). However, after adjusting for socioeconomic characteristics and health-related factors (physical activity, diet quality measured by healthy eating index), the association between food insecurity and overall mortality was no longer statistically significant. Food insecurity was associated with a greater risk of overall mortality among cancer survivors. Further studies are needed to confirm these findings and evaluate whether the observed association represents a causal phenomenon and, if so, whether the effect is modifiable with food assistance programs.

A population-based propensity score matching analysis of risk factors and the impact on survival associated with refusal of cancer-directed surgery in patients with prostate cancer

Cancer-directed surgeries (CDS) play a crucial role in prostate cancer (PCa) management along with possible survival and therapeutic benefits. However, barriers such as socioeconomic factors may affect patients’ decision of refusing recommended CDS. This study aimed to uncover risk factors and the impact on survival associated with CDS refusal. We retrospectively reviewed the Surveillance, Epidemiology, and End Results database for patients diagnosed with PCa between 2000 and 2019. Multiple sociodemographic and clinical characteristics were extracted to assess predictors for physicians’ surgical recommendations and patients’ surgical refusal, respectively. Propensity score matching was performed to balance the covariates. The impact of surgical refusal on mortality risk was also investigated. A total of 185,540 patients were included. The physician’s recommendation of CDS was significantly influenced by the patient’s age, race, income, home location, diagnosis year, Gleason score, prostate-specific antigen (PSA), and TNM stage. About 5.6% PCa patients refused CDS, most of whom were older, non-White race, lack of partners, living outside of metropolitan areas, with higher PSA or lower clinical TNM stage. Patients who refused CDS had an increased risk of cancer-specific mortality and overall mortality than those who performed CDS. Physicians may weigh a host of sociodemographic and clinical factors prior to making a CDS recommendation. Patients’ refusal of recommended CDS affected survival and was potentially modifiable by certain sociodemographic factors. Physicians should fully consider the hindrances behind patients’ CDS refusal to improve patient-doctor shared decision-making, guide patients toward the best alternative and achieve better outcomes.

Implications of Pretreatment Serum Carcinoembryonic Antigen Levels and Perineural Invasion with Staging, Prognosis, and Management in Stage I-III Colon Cancer after Surgery: A Retrospective Cohort Study in the SEER Database.

Pretreatment levels of serum carcinoembryonic antigen (CEA) and perineural invasion (PNI) are related to poor prognosis in colon cancer. We analyzed the CEA and PNI (defined as incorporation of carcinoembryonic antigen and perineural invasion (CP)-stage), which are included in the Tumor-Node-Metastasis (TNM) staging system of the American Joint Committee on Cancer (AJCC), and evaluated the survival prognosis of patients treated with surgery in I-III stage colon carcinoma. We employed a retrospective study for eligible colon carcinoma patients obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Kaplan-Meier curve and Multivariate Cox regression analysis were used to analyze different TNM-CP stages for the cancer-specific survival (CSS) probabilities in colon cancer. In our study, CEA levels and PNI were significant prognostic factors (p < 0.05), and the newly proposed CP-stage was an independent prognostic index in stage I-III colon carcinoma after surgery. Multivariate Cox regression analyses indicated that CP1-stage was related to a 63.9% increased risk of cancer-specific mortality (hazard ratio (HR): 1.639, 95% confidence interval (CI): 1.544-1.739, p < 0.001), compared with CP0-stage in colon cancer. In respective TNM stages, the CP0-stage had an advantage over the CP1-stage for CSS (p < 0.001). Moreover, CP1-stage patients with node-negative colon cancer were contacted with similar or worse survival in comparison to CP0-stage patients with node-positive. For postoperative patients with stage I-III colon cancer, our study indicated that the CP stage is a significant prognostic factor for CSS, which deserves more clinical attention. It's worth noting that including the CP stage in the AJCC TNM staging system of colon carcinoma is beneficial to the survival prediction and clinical treatment.

Optimal timing for the first cystoscopic follow-up using time-to-treatment initiation analysis of oncologic outcomes in primary non-muscle invasive bladder cancer

Various guidelines recommend the first follow-up cystoscopy at 3 months; however, no data exist on the optimal timing for initial follow-up cystoscopy. We tried to provide evidence on the timing of the first cystoscopy after the initial transurethral resection of bladder tumor (TUR-BT) for patients with non-muscle invasive bladder cancer (NMIBC) using big data. This was a retrospective National Health Insurance Service database analysis. The following outcomes were considered: recurrence, progression, cancer-specific mortality, and all-cause mortality. Exposure was the time-to-treatment initiation (TTI), a continuous variable representing the time to the first cystoscopy from the first TUR-BT within 1 year. Additionally, we categorized TTI (TTIc) into five levels: < 2, 2–4, 4–6, 6–8, and 8–12 months. A landmark time of 1 year after the initial TUR-BT was described to address immortal-time bias. We identified the optimal time for the first cystoscopy using Cox regression models with and without restricted cubic splines (RCS) for TTI and TTIc, respectively. Among 26,660 patients, 16,880 (63.3%) underwent cystoscopy within 2–4 months. A U-shaped trend of the lowest risks at TTI was observed in the 2–4 months group for progression, cancer-specific mortality, and all-cause mortality. TTI within 0–2 months had a higher risk of progression (aHR 1.36; 95% confidence intervals [CI] 1.15–1.60; p < 0.001) and cancer-specific mortality (aHR 1.29; 95% CI 1.05–1.58; p = 0.010). Similarly, TTI within 8–12 months had a higher risk of progression (aHR 2.09; 95% CI 1.67–2.63; p < 0.001) and cancer-specific mortality (aHR 1.96; 95% CI 1.48–2.60; p < 0.001). Based on the RCS models, the risks of progression, cancer-specific mortality, and all-cause mortality were lowest at TTI of 4 months. The timing of the first cystoscopy follow-up was associated with oncologic prognosis. In our model, undergoing cystoscopy at 4 months has shown the best outcomes in clinical course. Therefore, patients who do not receive cystoscopy at approximately 4 months for any reason need more careful follow-up to predict a poor clinical course.

Cancer-Specific Mortality Odds Ratios in the Food, Accommodation, and Beverage Activities in Italy.

This study investigated cancer-specific mortality risks of workers employed in food, accommodation and beverage (FAB) activities. Methods: We performed a case-control study based on countrywide mortality and National Social Insurance data. Adjusted cancer-specific mortality odds ratios (MOR) were calculated. We modeled occupational exposure as "ever/never been employed" in FAB activities, using other sectors as reference. Analysis was performed by gender, length of employment and year of smoke banning. Results: About 20,000 cancer deaths in FAB were analyzed. Working in restaurants was positively associated with cancer of lung (MOR = 1.24), bladder (MOR = 1.24), pharynx, and larynx. Accommodation was associated with cancer of pharynx (MOR = 1.46), while beverage with cancer of liver (MOR = 1.22). Gender, length of employment and smoke banning were found effective in modifying some risks. Conclusions: Workers in FAB sectors were at risk for several cancers.

Survival outcome and optimal candidates of primary tumor resection for patients with metastatic medullary thyroid cancer.

Medullary thyroid cancer (MTC) often exhibits aggressive growth with distant organ metastasis, leading to poor survival. The question of whether primary tumor resection (PTR) is beneficial for patients with metastatic MTC remains a subject of debate. In this study, we evaluated the prognostic significance of organ-specific metastases and the number of metastatic organs in these patients, and we also conducted an analysis to determine the therapeutic value of PTR in managing this rare malignancy. Patients initially diagnosed with metastatic MTC were identified within the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable Cox proportional hazards regression models were performed to identify survival predictors. Survival outcomes were calculated using the Kaplan-Meier method and compared using the log-rank tests. A total of 186 patients with metastatic MTC at initial diagnosis from 2010 to 2020 were included. Bone, lung and liver were the most common metastatic organs. Patients with brain metastasis had significantly worse overall survival (OS) (p = 0.007) and cancer-specific survival (CSS) (p = 0.0013). Among all patients, 105 (56.45%) underwent PTR, and this group showed reduced overall mortality (OM) and cancer-specific mortality (CSM) (all p < 0.05). When analyzing different metastatic patterns, PTR significantly lowered the risk of OM and CSM for patients with bone, lung, liver, or distant lymph node (DLN) involvement (all p < 0.05). Additionally, among patients with one or two metastases, those undergoing surgical resection were significantly associated with favorable OS (p = 0.008) and CSS (p = 0.0247). PTR may confer therapeutic benefits for carefully selected individuals with metastatic MTCs. To integrate these insights into clinical decision-making settings, it is imperative to undertake multicenter prospective studies in the future.

356 The Effect of Regional Anesthesia on Breast Cancer Recurrence

OBJECTIVES/GOALS: To determine the impact of regional anesthesia (RA) on rates of breast cancer recurrence, breast cancer specific mortality, post mastectomy pain syndrome, and chronic opioid use among patients who received regional anesthesia during primary breast cancer surgery. METHODS/STUDY POPULATION: Study population: Patients who underwent primary breast cancer surgery at Emory University and among a national patient cohort. Methods: This is a retrospective analysis of patients who underwent primary breast cancer surgery. Invasive breast cancer specific survival &amp; breast cancer-specific survival will be estimated using Kaplan-Meier method and compared among patient groups. Cox proportional hazards will be utilized to estimate the unadjusted &amp; adjusted risk of breast cancer recurrence and breast cancer-specific mortality between the two groups. RESULTS/ANTICIPATED RESULTS: We will present on our work comparing rates of breast cancer recurrence among patients who received regional anesthesia compared to patients who did not. DISCUSSION/SIGNIFICANCE: This study aims to establish the effect of regional anesthesia on breast cancer recurrence,breast cancer specific mortality, post mastectomy pain syndrome, and chronic opioid use following primary breast cancer surgery.

Abstract 2239: Comparative effectiveness of cystoscopy surveillance strategies on mortality in non-muscle invasive bladder cancer: A target trial emulation using real-world data

Abstract Background: More than 60,000 U.S. adults are diagnosed with non-muscle invasive bladder cancer (NMIBC) each year. These patients are recommended to undergo surveillance via repeated cystoscopies. However, the ideal frequency of post-diagnostic cystoscopy surveillance remains unknown, and efforts are underway to de-escalate surveillance given uncertainty regarding its effect on mortality. We therefore aimed to compare the effectiveness of different post-diagnostic cystoscopy surveillance strategies on bladder cancer specific mortality. Methods: We used observational data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linkage to emulate a target trial, i.e., a hypothetical, pragmatic randomized trial that would answer our causal question. Eligible individuals were aged 66 years or older, diagnosed with NMIBC (Ta, Tis, or T1) classified as urothelial carcinoma between January 1, 2000 and December 31, 2017, and had completed their first post-diagnostic cystoscopy. We compared 10-year risks of bladder cancer specific mortality under cystoscopy surveillance every 3, 6, and 12 months separately among individuals at low, intermediate, and high risk. We estimated mortality risks using inverse probability weighted pooled logistic regression. Results: Among 58,004 eligible individuals, the median age at diagnosis was 77 years (interquartile range: 72, 82) and 75.6% were male. Over the 10 year follow-up period, 4,977 bladder cancer deaths occurred. Among individuals at high risk, the estimated 10-year bladder cancer mortality risks were 24.5% under the 3 month strategy, 26.6% under the 6 month strategy, and 27.3% under the 12 month strategy. Compared with cystoscopy every 3 months, the risk differences were 2.1% (95% confidence interval [CI]: -0.3, 3.8) for cystoscopy every 6 months, and 2.8% (95% CI: 1.0, 4.4) for cystoscopy every 12 months. For patients in the intermediate risk group, 10-year bladder cancer mortality risks were 14.4% under the 3 month strategy, 15.1% under the 6 month strategy, and 15.9% under the 12 month strategy. The risk differences were 0.7% (95% CI: -0.6, 2.0) for 6 vs. 3 months and 1.6% (95% CI: 0.3, 2.7) for 12 vs. 3 months. Among individuals at low risk, these mortality risks were 8.3% under the 3 month strategy, 9.2% under the 6 month strategy, and 9.6% under the 12 month strategy. Risk differences were 1.1% (95% CI: -0.1, 2.5) for 6 vs. 3 months and 1.5% (95% CI: 0.2, 3.0) for 12 vs. 3 months. Conclusions: We estimated that more frequent cystoscopy may result in clinically meaningful reductions in bladder cancer mortality among high risk patients. Among low and intermediate risk patients, more frequent cystoscopy may result in modest absolute risk reductions. Decision-makers should also consider the clinical and financial burden and risk of complications associated with more frequent surveillance. Citation Format: Emma E. McGee, Xabier García de Albéniz, A. Heather Eliassen, Kendrick Yim, Barbra A. Dickerman, Mark A. Preston, Miguel Hernán. Comparative effectiveness of cystoscopy surveillance strategies on mortality in non-muscle invasive bladder cancer: A target trial emulation using real-world data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2239.