Low-risk Cancer Research Articles

Assessing the impact of contraceptive use on reproductive cancer risk among women of reproductive age—a systematic review

BackgroundContraceptives play a crucial role in women's reproductive health, their hormonal components may be linked to cancer risks, specifically breast, and gynecological cancers. Given the high usage rates of hormonal contraceptives, it is vital to systematically evaluate their potential impact on cancer outcomes, especially among women with a family history of gynecological cancers.ObjectivesThis study aims to evaluate the evidence on the association between modern contraceptive use and the risk of breast and reproductive cancers (ovarian, endometrial, and cervical cancer) among women of reproductive age, to inform healthcare providers, women, and program managers about cancer outcomes related to contraceptive use.MethodsA systematic review was conducted according to PRISMA guidelines. Searches were performed in databases such as CINAHL, OVID Medline, EMBASE, and more from inception to February 2022. Eligible studies included randomized controlled trials, cohort studies, and case-control studies that compared cancer outcomes between contraceptive users and non-users. Data extraction, quality assessment, and meta-analyses were conducted following predefined protocols. Subgroup and sensitivity analyses examined variations in contraceptive methods, doses, and duration.ResultsA total of 51 studies were included, comprising 2 RCTs and 49 observational studies. The review identified a significant reduction in ovarian and endometrial cancer incidence among contraceptive users. Hormonal contraceptive users had a 36% lower risk of ovarian cancer (RR 0.64, 95% CI 0.60–0.68), with specific reductions seen in combined oral contraceptive users (RR 0.62, 95% CI 0.57–0.68) and hormonal IUD users (RR 0.68, 95% CI 0.48–0.96). The rate ratio of cervical cancer was higher among non- users compared to hormonal contraceptive users when we pooled the results (1.28, 95% CI 1.21, 1.35). No significant association was found between contraceptive use and breast cancer risk among healthy women (RR 1.00, 95% CI 0.94–1.06). However, BRCA1/2 mutation carriers using oral contraceptives showed a heightened risk of breast cancer (HR 1.39, 95% CI 1.15–1.67).ConclusionThis systematic review highlights the protective effects of modern contraceptives against ovarian and endometrial cancers while identifying an increased risk of cervical. No significant breast cancer risk was found for healthy women, but BRCA1/2 mutation carriers faced increased risks. These findings underscore the need for personalized contraceptive counselling that considers cancer risk factors. Further research is needed to explore contraceptive impacts across different genetic profiles and dosing regimens.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, Prospero (CRD42022332647).

Abstract 4123540: Cardiovascular Health and Cancer Incidence and Mortality: NHANES-III and -Continuous study

Background: Cancer and cardiovascular disease (CVD) are the leading causes of death worldwide. Limited evidence is available regarding the relationship between CVD, cardiovascular risk factors (CVRF), and cancer mortality; and how CVRF further modify that relationship. Methods: The first part included 438 and 2100 CVD patients aged 65+ from NHANES-III and Continuous (1999-2016) datasets, respectively. Competing risk models with subdistribution hazards ratio (aHR) were used to identify risk factors for cancer incidence. The second part included 44,591 adult individuals from NHANES-Continuous merged with Medicare and National Death Index mortality data until the end of 2018. We included individuals with no history of cancer at baseline. We used competing risk modeling to test the relationship between CVD at baseline and cancer mortality. We also conducted a comprehensive risk factor analysis. Results: In the first part (Figure), females in NHANES-III had lower cancer risk (aHR 0.39, P=0.001) compared to males. Poor physical activity was associated with increased cancer risk in both datasets (aHR 2.59 in NHANES-III, aHR 1.59 in Continuous). In NHANES-Continuous, age (aHR 1.07, P<0.001) and current smoking (aHR 2.55, P=0.001) showed a significant association with developing cancer. No other factors investigated showed significant associations. In the second analysis (Table), the included sample size represented 1,738,423,317 individuals (52% females, 67% non-Hispanic Whites, and 9% Hispanics). Competing risk modeling showed a significantly higher risk of cancer mortality in individuals with CVD (aHR 1.37, 95% CI 1.07-1.76, P=0.01) after adjusting for age, sex, and race/ethnicity. Notably, cancer mortality increased with aging (aHR 1.08, 95%CI 1.05-1.11, P<0.0001), current smoking status (aHR 6.78, 95%CI 3.43-13.42, P<0.0001), and obesity (aHR 2.32, 95%CI 1.13-4.79, P=0.02). Finally, a significant interaction (P=0.034) was found where those with CVD and obesity showed higher cancer mortality than those with normal BMI (aHR, 95%CI 1.03-2.91, P=0.04). Conclusions: Our study highlights the close relationship between cardiovascular health and cancer, including among CVD patients. Our findings suggest that physical activity and obesity may play a significant role in cancer incidence and mortality among the general population and CVD patients. These findings emphasize the need for more proactive approach in the management of shared risk factors for CVD and cancer.

Abstract 4138519: A Scoping Review Exploring Cardiovascular Risk and Health Metrics and Cancer Prediction

Introduction: Cardiovascular disease (CVD) and cancer are leading causes of morbidity and mortality. Since they share risk factors, it is plausible that CVD risk scores and cardiovascular health (CVH) metrics could also be used to predict cancer. Research Question: What is the relationship between established CVD risk scores and CVH metrics and the incidence of cancer? Methods: A librarian searched four databases (Embase, PubMed, Scopus, Web of Science: Core) in February 2024 without language restriction. Using Covidence, two reviewers independently screened the titles, abstracts, and full texts of the retrieved articles based on the inclusion criteria (prospective observational studies, adults aged ≥18 years, reported incidence of any type of cancer as an outcome, and used at least one CVD risk score or CVH metric as an exposure). A third reviewer resolved conflicts. The characteristics of the studies retained after screening and the summary estimates of the associations were extracted using Excel. Results: Of the 4,165 records screened, 13 studies (reporting 14 CVD or CVH metrics) were included. The heterogeneity in the scales (comparison group) precluded a meta-analysis. Four studies evaluated CVD risk scores (Atherosclerotic Cardiovascular Disease [ASCVD], Framingham Risk Score, Systematic Coronary Risk Evaluation), and 10 reported CVH metrics (American Heart Association [AHA] Life’s Simple 7, AHA Life’s Essential 8). Sample size ranged from 1,880 to 342,226, with median follow-up from 8.1 to 29.6 years. Most of the studies included more women than men (61.5%) and mean age ranged from 44.8 to 72 years. The majority of studies included all cancer types (71.4%), including breast, lung, colorectal, and prostate cancer subtypes, and the total number of cancer events ranged from 387 to 11,643. Studies utilizing CVD risk scores consistently reported that individuals with a higher CVD risk, developed any type of cancer, with hazard ratios (HRs) ranging from 1.02 to 3.71, and studies employing CVH metrics generally indicated an ideal CVH is associated with a lower cancer risk, with HRs ranging from 0.49 to 0.95. Conclusion: Despite heterogeneity in CVD risk metrics and cancer subtypes, most studies reported that higher CVD risk scores or worse CVH metrics may increase future cancer risk. More rigorous studies are needed focusing on specific CVD risk metrics and cancer types of cancer to produce evidence suitable for a meta-analysis.

Examining the Effect of Parental COVID-19 Vaccination Prior to Birth and the Association Between COVID-19 and Cancer in Children Under Six.

The biology of COVID-19 has intricate links to childhood cancer, exacerbated by pandemic disturbances. This research aims to explore the association between childhood cancer in children under 6 years old and COVID-19 immunisation, in addition to the effects of vaccination on parents before delivery. The study employs a case-control approach, gathering informed consent and matching factors like age, marital status, and socioeconomic status between cases and controls. A survey was distributed, culminating in 191 children under six, with data from 136 diagnosed cancer cases collected in 2023, adhering to methodological standards in epidemiological research. The analysis utilised SPSS28, employing chi-square testing and logistic regression. Chi-square testing confirmed a significant rise in childhood cancer rates post-COVID-19 pandemic compared to pre-pandemic rates. Key factors influencing cancer incidence include the mother's age at childbirth, parental vaccination history before pregnancy, maternal vaccination details during pregnancy, the child's COVID-19 infection status, and maternal marriage age. Notably, younger mothers faced higher COVID-19 infection risks, but vaccination appears to mitigate paediatric cancer risk. The post-pandemic surge in childhood cancer underscores a complex interplay of early exposures and maternal viral infections. Emphasising vaccination's protective effects before and during pregnancy, the study advocates integrating vaccination into maternal health programs. Public health measures should promote immunisation and address socioeconomic inequalities to lower paediatric cancer risk, aligning with previous studies linking parental health behaviours to childhood cancer incidence.

Predictive factors of immediate continence after conventional robot-assisted radical prostatectomy: a single-institution retrospective study.

To assess the predictive factors of immediate urinary continence after robot-assisted radical prostatectomy. This study included 282 patients who underwent conventional robot-assisted radical prostatectomy at our institution from April 2019 to March 2024. The primary outcome was immediate urinary continence, defined as the absence of urine leakage immediately after urinary catheter removal on postoperative day 6 or 7. In addition, the immediate urine loss rate, defined as the 24-h urine loss volume divided by the total urine volume after catheter removal, was calculated. The multivariable logistic model was used to assess the possible predictive factors of immediate continence (urine loss rate of 0%). The factors included age, body mass index, Charlson Comorbidity Index, pre-existing lower urinary tract symptoms, presence of an inguinal hernia, prostate volume, membranous urethral length, stratified cancer risk, surgeon's experience, and nerve-sparing procedure. In addition, a multiple linear regression model was established to investigate the associations of the same predictors with immediate urine loss rate (%). We also presented our techniques to achieve immediate continence. The patients' median age was 70 (interquartile range: 63.0-73.0) years. Approximately 39% (n = 111) of patients presented with immediate continence. Age, inguinal hernia, membranous urethral length, and low risk for prostate cancer were associated with immediate continence. These were also statistically significant predictors of immediate urine loss rate. Our study identified factors predicting immediate urinary continence after conventional robot-assisted radical prostatectomy. This information is potentially valuable for preoperative counseling in patients undergoing robot-assisted radical prostatectomy.

Benefit of systemic therapy in MINDACT patients with small, ER-positive, HER2-negative breast cancers

Small, hormone receptor-positive (HR+), HER2-negative (HER2-), lymph node-negative breast cancers are associated with relatively low rates of disease recurrence and have therefore been underrepresented in clinical trials assessing the effects of systemic therapy. Consequently, it remains uncertain if this patient population derives benefit from these treatments. For this exploratory analysis, we selected MINDACT (NCT00433589) patients with a HR+, HER2-, T1ab (≤1 cm) tumor and negative lymph nodes. Patients with discordant clinical risk and MammaPrint genomic risk classification were randmomized to receive chemotherapy based on either the clinical or the genomic risk assessment. Endocrine therapy treatment was based on local guidelines. 715/6693 (10.7%) MINDACT patients had HR+, HER2-, T1abN0 breast cancer and were included in this analysis. All were clinically low-risk, 124/715 (17.3%) were genomic high-risk. For genomic high-risk tumors, 8-year distant metastasis-free survival (DMFS) was 92.9% (95% CI 86.2–96.4%) compared to 95.0% (95% CI 92.8–96.6%) for genomic low-risk tumors. For genomic high-risk tumors treated with or without chemotherapy, 8-year DMFS was 89.2% (95% CI 73.6–95.8%) and 94.1% (95% CI 82.9–98.1%), respectively. For genomic low-risk tumors, the 8-year DMFS and disease-free survival (DFS) were 96.1% (95% CI 93.4–97.6%) and 89.3% (95% CI 85.5–92.2%) when treated with endocrine therapy and 92.9% (95% CI 87.9–95.9%) and 79.4% (95% CI 72.5–84.8%) without. In conclusion, although the number of randomized patients is small, patients with small, genomic high-risk breast cancer did not seem to derive benefit from chemotherapy. Endocrine therapy was associated with improved outcomes even in genomic low-risk breast cancers.

Human papillomavirus-based cervical screening and long-term cervical cancer risk: a randomised health-care policy trial in Sweden.

Human papillomavirus (HPV)-based cervical screening is a globally recommended public health policy. Randomised clinical trials find superior performance of primary HPV-based screening compared with cytology for preventing cervical cancer. However, additional evidence from real-world public health policies is needed. In preplanned secondary analysis of a randomised health-care policy trial in Sweden we aimed to evaluate which policy provided better protection against invasive cervical cancer, after two full rounds of screening. The organised cervical screening programme in the capital region of Sweden invited all women aged 30-64 years and eligible for screening to a randomised health-care policy trial of HPV-based versus cytology-based screening. During 2014-16, 395 725 eligible women were randomly assigned (non-concealed) to either policy and the invasive cervical cancer incidences over 8 years of follow-up were compared. Intention-to-screen analyses included all invited women and per-protocol analyses the women that attended baseline screening according to protocol. This trial is registered with ClinicalTrials.gov, NCT01511328. Women invited to HPV-based cervical screening had a 17% lower invasive cervical cancer risk compared with women invited to cytology (hazard ratio [HR] 0·83, 95% CI 0·70-0·98). Women participating in HPV-based screening had a 28% lower invasive cervical cancer risk compared with women participating with cytology (HR 0·72, 95% CI 0·54-0·95). Adverse events were a higher number of referrals to colposcopy with biopsy in the HPV policy (15 832 [7·5%] of 212 199 in intention to screen analyses and 9968 [9·0%] of 110 176 per protocol at baseline) than in the cytology policy (12 650 [6·9%] of 183 120 in intention to screen analyses, and 7179 [7·9%] of 90 821 per protocol at baseline). Women who were HPV-negative at baseline had invasive cervical cancer risks of 1·3 (95% CI 0·6-2·4) per 100 000 person-years, whereas the risk for women with normal cytology was 9·1 (6·7-11·8) per 100 000 person-years. HPV-positive women with negative cytology triage had invasive cervical cancer risks of 79·2 per 100 000 person-years and HPV 16 or HPV 18-positive women with negative cytology triage had risks of 318·2 per 100 000 person-years. This randomised policy trial found HPV-based screening to be superior for preventing invasive cervical cancer in the real-world setting. A single baseline HPV-negative test was associated with a very low invasive cervical cancer risk after 8 years. However, HPV positivity with negative cytology triage was associated with high invasive cervical cancer risks. Region Stockholm, Swedish Cancer Society, and European Union Horizon 2020.

Thyroid-stimulating hormone suppression in low-risk papillary thyroid cancer: a large-scale retrospective analysis of real-world data

Over 500,000 new cases are diagnosed with papillary thyroid cancer (PTC) globally per year, of whom the vast majority are in the low-risk stratification. Although thyroid-stimulating hormone (TSH) suppression is traditionally recommended for all postoperative PTCs in current guidelines, its necessity remains highly controversial in low-risk patients. Since relevant recommendations in current guidelines are still empirical, we aim to provide a direct, large-scale, real-world evidence. This large-scale real-world retrospective study included 11,140 low-risk PTC patients from two Chinese large-volume centers (Fudan University Shanghai Cancer Center [FUSCC] and Cancer Hospital of Chinese Academy of Medical Sciences [CH-CAMS]) treated from January 1, 2000 to June 30, 2022. The mean TSH level was calculated based on postoperative serum TSH values during follow-up. The primary outcome was the association between postoperative TSH level and structural recurrence assessed by Kaplan-Meier, log-rank, multivariate Cox regression analyses and equivalence testing by Two One-Sided Tests (TOST) procedure. Propensity score matching (PSM) was used to adjust for confounders among groups. A total of 11,140 patients with low-risk PTC were included with a median follow-up of 70 months. Based on the mean TSH level, we classified these patients into ≤0.5 (n=1,504, 13.5%), (0.5-1] (n=4,336, 38.9%), (1-2] (n=4,285, 38.5%), (2-3] (n=704, 6.3%) and >3 (n=311, 2.8%) mU/L groups. After PSM adjusting for age, sex, T and N stage, 8991 patients were included in further analysis, for whom the log-rank analyses showed no significant differences between any two groups (all P>0.05) in recurrence-free survival (RFS), locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS), and suppressed TSH was not associated with tumor recurrence in the multivariate Cox analysis (TSH > 2 group vs TSH ≤ 2 group: HR=1.30, 95% CI=0.85-2.01, P=0.23). Furthermore, the TOST equivalence tests showed that tumor recurrence status of any two TSH groups were statistically comparable (all Bonferroni-corrected P values<0.005). Subgroup multivariate analyses showed that TSH level did not impact tumor recurrence regardless of age, tumor size, lymph node metastasis, multifocality, surgical extent, biochemical evidence. Our results suggested that postoperative TSH level was not associated with tumor recurrence in patients with low-risk PTC, for whom deliberate TSH suppression may be exempted to avoid potential secondary complications. Maintaining a TSH level within the normal range may be safe for these patients. The study was supported by the National Natural Science Foundation of China (82072951 to Y.W.; 82373008 to X.S.), Shanghai Hospital Development Center (SHDC2020CR6003-001 to Y.W., SHDC2024CRI087 to Y.-J.W.), the Science and Technology Commission of Shanghai Municipality (22Y21900100/23DZ2305600 to Y.W.; 23ZR1412000 to X.S.), the Shanghai Anticancer Association Foundation (SACA-AX202213 to Yu Wang), Shanghai Municipal Health Commission and Shanghai Medicine and Health Development Foundation (WJWRC202302 to X.S.).

From weight loss to cancer treatment: Fasting as an adjuvant anticancer therapy

The number of studies that have been conducted on the possible benefits of different types of fasting or calorie restriction on cancer therapy, including the likelihood that these treatments lessen side effects, has been limited. However, the results are nevertheless promising. Chemotherapy’s adverse effects have led to a quest for options that reduce reliance on it. The susceptibility of tumorous cells to specific metabolites and nutrient deficiency is increasingly recognized as a key characteristic of the disease. This review delves into the data on various fasting methods and calorie restriction in rodents and humans, with a focus on biological adaptations that could potentially lower cancer risk or enhance cancer treatment results. We also emphasize recent scientific developments regarding the use of prolonged fasting and fasting-mimicking diets as a possible additional treatment for patients receiving immunotherapy or other treatments. This approach shows promise in enhancing treatment effectiveness, preventing resistance, and minimizing side effects. This study proposes that combining fasting and calorie restriction with chemotherapy, immunotherapy, or other therapies might be a potential technique to improve treatment efficacy, avoid resistance, and reduce adverse effects.

Advancing prostate cancer detection: High-accuracy urine test distinguishes between high and low-risk cancers

Prostate cancer remains one of the leading causes of cancer-related deaths among men. The standard method for early detection involves measuring Prostate-specific antigen (PSA) levels in the blood, with elevated PSA levels prompting further diagnostic procedures, such as a prostate biopsy. While effective, biopsies can be painful and carry risks of complications such as fever and urinary tract infections. To reduce unnecessary biopsies, researchers have sought alternative diagnostic methods. In recent years, a urine test was developed for early-stage prostate cancer detection. However, this test struggled to differentiate between aggressive and slow-growing cancers, the latter of which often require minimal treatment and are managed through active surveillance. To address this limitation, scientists at Wunderkind University have significantly enhanced the urine test. By analysing the genomes of thousands of prostate cancer patients, they identified a panel of 16 genes detectable in urine that can effectively distinguish between high-risk and low-risk cancers. When applied to individuals with elevated PSA levels, this improved test demonstrated an impressive 97% accuracy in identifying advanced prostate cancer. This advancement holds great promise for reducing unnecessary biopsies and improving patient outcomes by accurately identifying those needing aggressive treatment versus those suitable for observation. This review paper will explore the development, validation, and clinical implications of this novel urine test, highlighting its potential to transform prostate cancer diagnostics and patient management.

Can Ki-67 serve as a suitable marker to indicate the necessity of staging diagnostics in cases of low-risk breast cancer?

For many years, staging tests have not been routinely employed for low-risk early breast cancer (EBC). However, the role of Ki-67 in determining the need for staging tests in low-risk EBC remains unclear. Our study aimed to assess the number and types of staging diagnostics, additional imaging, false-positive results, and rate of distant metastases in low-risk EBC with low and high Ki-67 (< / ≥ 25%). This is a retrospective, single institution cohort study. All patients with newly diagnosed low-risk breast cancer at the University Medical Center in Freiburg in 2017 and 2021 were included. Low-risk was defined as clinical tumor stage T1/2, node negative (N0), hormone receptor positive, HER2 negative, asymptomatic EBC. Information on demographics, clinical and pathological characteristics, as well as number and type of performed staging diagnostics was obtained. Rate and type of additional imaging or follow-up diagnostics due to suspicious findings was analyzed. The patients were divided into two groups (Ki-67 < and ≥ 25%) and rates of distant metastases, performed staging diagnostics and false positive rates were compared. A total of 189 patients with low-risk EBC were identified, with 54% (n = 102) having Ki-67 < 25% and 46% (n = 87) having Ki-67 ≥ 25%. Risk for distant metastases was 0% in Ki-67 < 25% and 1.1% in patients with Ki-67 ≥ 25% (p = 0.46). Due to suspicious findings in the initial staging diagnostic, additional imaging was required for 11.8% (n = 12) of patients with Ki-67 < 25% compared to 19.5% (n = 17) of patients with Ki-67 ≥ 25% (p = 0.16). False positive rates did not differ significantly between the two groups (7.6% in Ki-67 < 25% vs. 9.8% in Ki-67 ≥ 25%; p = 0.55). Distant metastases are rare in low-risk EBC. All in all, staging diagnostics should not be routinely employed in this patient population. Only patients with high Ki-67 developed distant metastases. In these cases, staging diagnostics may be discussed with the patient.

Childhood-to-adulthood body size trajectory and cancer risk: a prospective cohort study

Abstract Background While excess weight in adulthood and childhood has been associated with increased cancer risk, the link between childhood-to-adulthood body size trajectories and cancer risk requires further investigation. Methods We used data from the UK Biobank, a prospective population-based cohort study. The main exposure was childhood-to-adulthood body size trajectory, constructed from self-reported body at age 10 (categories: thinner, average, and plumper than average) and measured body mass index (BMI) at recruitment (normal weight, overweight, and obese). Primary outcome was obesity-related cancer (13 different cancer types). Results During a median follow-up of 11.7 years, 21,289 participants developed obesity-related cancers. Having a larger body size at age 10 was strongly associated with being overweight or obese in adulthood. Compared to participants with average childhood to normal adulthood body size trajectory, all trajectories ending in overweight or obesity in adulthood were strongly associated with an increased risk of obesity-related cancers. The strength of the association was mostly determined by adulthood BMI, and similar patterns were observed for colorectal, endometrial, kidney, pancreatic and esophageal cancer. However, a larger body size in childhood was associated with a lower risk of postmenopausal breast cancer. Conclusions Although a larger body size in childhood predisposes to overweight and obesity in adulthood, it does not necessarily predispose to an increased obesity-related cancer risk if measures to maintain a healthy weight are taken in adulthood. Key messages • While larger body size in childhood predisposes individuals to overweight and obesity in adulthood, maintaining a healthy weight in adulthood may help mitigate the risk of obesity-related cancers. • Our findings highlight the importance of preventing and reducing overweight and obesity in adulthood for primary cancer prevention.

Long-term changes in frailty and incident atrial fibrillation: multicenter prospective cohort study

Abstract Background Atrial fibrillation is the most common sustained cardiac arrhythmia and is prevalent among the elderly. Previous findings indicated a higher prevalence of AF in frail adults and frailty prevalent in AF patients. However, the association between dynamic changes of frailty and risk of new-onset AF is unclear. Purpose We aimed to investigate the associations of long-term changes in frailty with incident AF. Its associations with heart failure (HF), coronary heart disease (CHD), and stroke were also evaluated as a secondary aim. Methods Over 50,000 participants from UK Biobank cohort were included, with available frailty index (FI) data and free of AF, HF, CHD or stroke in both baseline and final follow-up assessments. Participants were categorized into nonfrailty, prefrailty and frailty based on their FI scores. Changes of frailty status from baseline to final follow-up assessment included alleviation, maintenance, and aggravation. Thus, transitions of frailty status included 7 categories: nonfrailty maintenance, nonfrailty aggravation (nonfrailty to prefrailty or frailty), prefrailty alleviation (prefrailty to nonfrailty), prefrailty maintenance, prefrailty aggravation (prefrailty to frailty), frailty alleviation (frailty to prefrailty or nonfrailty), and frailty maintenance. FI in baseline and follow-ups are used to calculate the trajectories of frailty (ΔFI). Cox proportional hazard models were used. Results Compared with nonfrailty at baseline, the HRs (95% CI) of AF for prefrailty and frailty were 1.32 (1.29, 1.36) and 1.89 (1.83, 1.96) in the multivariable-adjusted model. During a median of 5.1 years of follow-up from the final assessment, 1729 cases of AF were recorded. Frailty trajectory analysis showed that even a 0.01 point/year increase in ΔFI was associated with 14% (95% CI 1.08-1.20) higher risk of AF, independent of baseline FI and the risk rose to 1.89 (1.45, 2.46) with per 0.05 point/year increase in ΔFI. This association was strengthened in low genetic risk of AF, but sex, age, smoking status, alcohol intake, obesity, hypertension, diabetes and cancer did not materially modify the associations. Moreover, compared with nonfrailty maintenance, sustained frailty had the highest risk of AF (HR 1.95, 1.61-2.36). Alleviation from frailty reduced the risk of AF by 30% (95%CI 0.53-0.94), compared to sustained frailty. These associations were similar in HF and CHD, however, not significant in stroke. Conclusions Middle aged and elderly people, including those with diabetes, obesity and hypertension, may gain substantial benefits in risk of AF, HF and CHD by becoming less frail or maintaining nonfrailty, irrespective of past frailty status and established risk factors, delivering public health implications for the necessity of early identification and timely interventions of frailty in heart health management.

Risk of subsequent primary cancers in bladder cancer survivors

We aimed to investigate the risk of bladder cancer (BCa) survivors developing or dying from 15 specific-subsequent primary cancers (SPCs). A total of 229,554 BCa survivors were identified from the Surveillance, Epidemiology, and End Results database. Incidence and mortality per 10,000 person-years, absolute excess risk (AER) per 10,000 person-years, standardized incidence ratios, and standardized mortality ratios were calculated. Among BCa survivors, 38,207 developed SPCs and 17,546 died of SPCs. The risk of developing and dying from SPCs was significantly high for 10 and 6 of the 12 common SPCs in men, respectively, while for 6 and 5 of the 14 common SPCs in women, respectively. The SPCs with high risk of development in men were colorectal, breast, liver, and pancreatic cancer, and the ones with high risk of death were liver and pancreatic cancer. Moreover, SPCs with a high risk of development or death among young BCa survivors include ureter, kidney and renal pelvis, and lung cancer. In addition, BCa survivors within 1 year of diagnosis have a significantly higher risk of development and death from ureter, kidney and renal pelvis, prostate, and cervix cancer, but a lower risk of prostate cancer than the general population after 5 years of diagnosis. Lung cancer had a significantly high risk of development but a low risk of death. Among BCa survivors, the risk of developing or dying from few SPCs is significantly high. These findings may provide an important basis for clinical follow-up of BCa survivors.

Multistage carcinogenesis in occupational cholangiocarcinoma: the impact of clonal expansion and risk estimation

BackgroundBoth mutation induction and clonal expansion of mutated cells cause cancer. The probability of cancer development depends on mutations, clonal growth rates, and carcinogenic mechanisms. A recent study showed cases of occupational cholangiocarcinomas that originate multifocally, with higher mutation burden levels than those in common cholangiocarcinomas. This study aimed to identify the effect of clonal expansion on and estimate the risk of occupational and common intrahepatic cholangiocarcinomas (ICCs) using a multistage model modified to include the effect of cell expansion at any carcinogenic stage.MethodsThe age-specific incidence of common ICC estimated from the Vital Statistics in Japan and the prognosis of ICC, and mutation frequencies of occupational and common ICC available from the previous report, were applied to a multistage model modified with cell proliferation effects. From the fittest model, the risk after exposure was estimated.ResultsThe required number of stages for carcinogenesis was estimated to be three based on the incidences and mutation frequencies of occupational and common ICCs. Based on this estimation, the predicted incidence curve under the model was similar to that estimated from the ICC mortality rate, except for older adults. The model indicated a minor effect of clonal expansion on the observed occupational ICC risk. It predicted a rapid decrease in ICC risk after the cessation of occupational exposure, although the time of clinical detection of cancer after the exposure was affected by latency. The model predicted an increase in cancer risk in older adults caused by cell expansion and common background mutations. However, the risk in older adults was overestimated in the case of common ICC; this divergence could influence occupational ICC cases.ConclusionsThree-stage ICC carcinogenesis has been proposed. The high mutation burden levels caused by occupational exposure led to an immediate incidence of cancer. After a long period of relatively low cancer risk, an increased risk in older adults was also predicted.

Association of SGLT2 inhibitors with incident cancer

AimIt remains unknown whether sodium-glucose cotransporter 2 inhibitors (SGLT2i) could be associated with incident cancer. MethodsWe analyzed individuals having diabetes and newly prescribed SGLT2i or dipeptidyl peptidase 4 inhibitors (DPP4i) in a large-scale epidemiological database. The primary outcome was the incidence of cancer. A propensity score matching algorithm was employed to compare the subsequent development of cancer between the SGLT2i and DPP4i groups. ResultsAfter 1:2 propensity score matching, 26,823 individuals (8,941 SGLT2i, 17,882 DPP4i) were analyzed. During the mean follow-up duration of 2.0 ± 1.6 years, 1,076 individuals developed cancer. SGLT2i administration was associated with a reduced risk of cancer (HR 0.80, 95 % CI 0.70–0.91). Particularly, SGLT2i administration was related to a lower risk of colorectal cancer (HR 0.71, 95 % CI 0.50–0.998). Our primary findings remained consistent across various sensitivity analyses, including overlap weighting analysis (HR 0.79, 95 % CI 0.66–0.94), inverse probability of treatment weighting 0.75 (95 % CI 0.65–0.86), and induction period settings 0.78 (95 % CI 0.65–0.93). The risk of developing cancer was comparable among individual SGLT2is (P-value of 0.1738). ConclusionOur investigation using nationwide real-world data demonstrated the potential advantage of SGLT2i over DPP4i in reducing the development of cancer in individuals with diabetes.

The Influence of Physical Training on Breast Cancer: The Role of Exercise-Induced Myokines in Regulating Breast Cancer Cell Growth and Survival.

The beneficial impact of physical training in lowering cancer risk is well known. However, the precise mechanisms linking physical training and cancer are not fully understood. Skeletal muscle releases various myokines that seem to possess a direct anti-tumor effect. Although breast cancer (BC) is the prevalent form of cancer among women on a global scale, only limited data are available about the secretion of myokines following exercise in patients with BC. To study the effects of exercise on BC, the blood samples of patients with varied stages of BC were analyzed after 12 weeks of resistance training with whole-body electromyostimulation (WB-EMS). Following the training period, we observed that resistance training helps these patients to improve their physical characteristics and performance function by increasing skeletal muscle mass and strengthening their hand grip. Notably, the patient's serum was found to inhibit the growth and promote the apoptosis of BC cells in vitro. Moreover, the conditioned medium collected from in vitro stimulated human myotubes using electric pulse stimulation (EPS), an in vitro simulation of WB-EMS training, induced the cell death of BC cells. These results highlighted the direct cancer-protective effects of activated skeletal muscle. In line with our observed effects of serum from exercise-trained pancreatic and prostate cancer patients, the growth of BC cells was notably inhibited when supplemented directly with recombinant myokines C-X-C motif ligand 1 (CXCL1), Interleukin 10 (IL10), and C-C motif chemokine ligand 4 (CCL4). Notably, treatment with these myokines also increased the expression of caspase 3/7 (Casp3/7), resulting in enhanced BC cell death. Our data strongly suggest that physical exercise has a positive impact on skeletal muscle mass and hand grip strength in BC patients, along with a significant anti-tumor effect in BC cells. This shows promising potential for considering sports and physical training as supportive therapies for achieving more impactful cancer treatment.

Adherence to lifelines diet is associated with lower lung cancer risk in 98,459 participants aged 55 years and above: a large prospective cohort study.

Lifelines Diet Score (LLDS) was developed based on the 2015 Dutch Dietary Guidelines and current international scientific evidence. As a dietary quality assessment tool, the LLDS aims to evaluate the association between the Lifeline diet and the risk of chronic diseases. However, the evidence linking LLDS to lung cancer risk is currently limited. Our objective was to explore whether adherence to the LLDS is associated with reduced incidence and mortality of lung cancer, including its major histological subtypes: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Data for this research were sourced from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Trial. The LLDS for each participant was calculated based on responses to the dietary history questionnaire (DHQ), and subsequently analyzed after being categorized into quintiles. The Cox proportional hazards regression model was utilized to compute the hazard ratios (HRs) and 95% confidence intervals (CIs) for both the incidence and mortality of lung cancer, SCLC and NSCLC. Additionally, stratified analyses were conducted to ascertain possible effect modifiers, and several sensitivity analyses were performed to evaluate the robustness of the findings. During the mean follow-up periods of 8.8 years for incidence and 15.1 years for mortality, we identified 1,642 new cases and 1,172 related deaths from lung cancer. Participants in the highest quartiles of LLDS compared to those in the lowest exhibited a reduced incidence (HRQ4:Q1 = 0.80, 95% CI = 0.68-0.94, P for trend = 0.003) and mortality (HRQ4:Q1 = 0.81, 95%CI = 0.67-0.98, P for trend = 0.009) of lung cancer. Furthermore, this negative association remained for SCLC incidence (HRQ4:Q1 = 0.55, 95% CI = 0.35-0.87, P for trend = 0.002) and mortality (HRQ4:Q1 = 0.42, 95% CI = 0.25-0.70, P for trend <0.001). The association between LLDS and the incidence and mortality of lung cancer is not influenced by pre-defined potential effect modifiers (all P interaction > 0.05). The sensitivity analyses substantiated the robustness of the results. In conclusion, our research indicates that among 98,459 U.S. adults aged 55 and older, adherence to the LLDS is linked to a diminished incidence and mortality of lung cancer.

Association of Radioactive Iodine Administration With Outcome Among Patients With Low-Risk Differentiated Thyroid Cancer: A Real-World Data Analysis.

Despite the generally favourable long-term prognosis of low-risk differentiated thyroid cancer (DTC), questions remain about disease-free survival (DFS) after initial treatment, particularly regarding the use of radioactive iodine (RAI). Although there are RCT trial confirming that RAI ablation therapy is not superior to follow-up in terms of the 3-year DFS rate in low-risk thyroid cancer, its longer-term prognosis remains to be established. The objective of this study was to assess the impact of RAI ablation on the presence of structural persistent/recurrent disease in patients with low-risk DTC. We retrospectively identified 720 low-risk DTC patients who had undergone total or near-total thyroidectomy (TT) at a tertiary medical centre between January 2008 and July 2018. Propensity scores were calculated using a multivariable logistic regression model that accounted for age, sex, tumour size, neck dissection, multifocality, capsular invasion and lymph node (LN) metastasis. We compared DFS between patients who received RAI and those who did not using log-rank tests and multivariate Cox analyses. Subgroup analyses were also conducted. Of the total cohort, 180 (25.0%) patients received RAI, while 540 (75.0%) did not before matching. The median follow-up duration was 59.5 months. After matching, the RAI group comprised 135 (39.8%) patients and the non-RAI group comprised 204 (60.2%) patients. In the entire cohort, the 5-year DFS rate was 97.6% for patients receiving RAI compared to 96.8% for those not receiving RAI (p = 0.704). In the matched cohort, the rates were 98.5% and 95.6%, respectively (p = 0.090). Matched multivariate Cox analysis demonstrated that RAI was neither significantly nor independently associated with DFS (hazard ratio [HR] = 0.29; 95% CI 0.06-1.37; p = 0.118). Further subgroup analyses reaffirmed that RAI ablation did not significantly reduce the risk of developing structural persistent/recurrent disease. Administering RAI ablation following TT did not result in improved DFS for low-risk DTC patients. Our findings suggest that decisions regarding RAI should be made judiciously to avoid overtreatment in this clinical scenario.

Loss of vimentin expression in preoperative biopsies independently predicts poor prognosis, lymph node metastasis and recurrence in endometrial cancer

BackgroundPrecise preoperative risk classification of endometrial cancer is crucial for treatment decisions. Existing clinical markers often fail to accurately predict lymph node metastasis and recurrence risk. Loss of vimentin expression has emerged as a potential marker for predicting recurrence in low-risk endometrial cancer patients. We assessed whether vimentin expression in preoperative biopsies predicts poor prognosis and lymph node metastasis in a large multicentre cohort.MethodsVimentin expression was evaluated using immunohistochemistry in 1483 patients diagnosed with endometrial cancer across 14 hospitals in Europe. Expression levels of vimentin were analyzed in conjunction with clinical characteristics for predicting disease-specific survival and lymph node metastases.ResultsVimentin loss was significantly associated with aggressive disease and poor survival. Adjusted for clinicopathological variables, vimentin remained independently prognostic with a hazard ratio (HR) of 1.68 (95% CI 1.16–2.42, P = 0.006). Vimentin expression remained independently prognostic in endometrioid endometrial cancer- and FIGO staged 1 patient. Interestingly, vimentin loss independently predicted lymph node metastases, with an HR of 1.83 (95% CI 1.13–2.95, P = 0.014).ConclusionsLoss of vimentin in preoperative biopsies serves as an independent predictor of poor prognosis and lymph node metastases. Incorporating vimentin as a clinical marker can improve risk stratification and treatment decisions.