Low-risk Cancer Research Articles

BREATH TEST TO DETECT WOMEN AT LOW RISK FOR BREAST CANCER: POTENTIAL CLINICAL AND ECONOMIC BENEFITS.

A breath test for volatile organic compounds has identified biomarkers associated with breast cancer. We evaluated the potential clinical and economic benefits of a breath test to detect women at low risk for breast cancer by comparing its negative predictive value (NPV) to the NPV of screening mammography. Sensitivity and specificity values for screening mammography were obtained from the Food & Drug Administration Mammography Quality Standards Act; Amendments to Part 900 Regulations Docket No. FDA-2013-N-0134. The high values were sensitivity = 79.0%, specificity = 88.9% and the low values were sensitivity = 66.0%, specificity = 88.9%. In two previous studies of 771 women undergoing mammography, breath testing identified breast cancer with sensitivity=84% and specificity = 68.6% in 178 asymptomatic women, and sensitivity=82% and specificity = 77% in 593 who were symptomatic. These values were projected to a hypothetical screening population of 100,000 asymptomatic women with average breast cancer prevalence of 450/100,000, in order to estimate the NPV and PPV (positive predictive value) for breath testing and screening mammography respectively. Breath test in asymptomatic women: NPV = 99.895% and PPV = 1.19%; in symptomatic women: NPV = 99.895% and PPV = 1.59%. For screening mammography, NPV = 99.83% and PPV = 2.82% (low values), increasing to NPV= 99.89% and PPV = 3.12% (high values). A negative breath test identified 68.3% of the screening population as having low risk of breast cancer, with NPV similar to mammography. Based on Medicare reimbursement rates, elimination of mammography in women with a negative breath test could reduce the annual cost of breast cancer screening by 38.9. In a hypothetical screening population, a negative breath test ruled out breast cancer with the same accuracy as a negative mammogram. A screening breath test could potentially eliminate the need for two thirds of all mammograms and reduce the costs of screening without increasing the risk of false-negative findings. If applied in clinical practice, this approach could potentially reduce the costs and burdens of breast cancer screening services, and benefit women by lessening the discomfort, anxiety, radiation exposure, and costs associated with mammography.

Australian males and females have similar rates of presentation for symptomatic and advanced thyroid cancer: Retrospective analysis of the Australian New Zealand Thyroid Cancer Registry.

Thyroid cancer is more commonly diagnosed in females, however recent research has challenged whether this finding is due to a true difference in biology or rates of diagnosis, with concerns that over-diagnosis may be a factor in differences. The rates of symptomatic versus incidental diagnosis by males and females is not well known. This study used the Australian and New Zealand Thyroid Cancer Registry (ANZTCR) to explore whether symptomatic presentation varies between sexes. Retrospective analysis on ANZTCR data between 2017 and 2022 was performed. Symptomatic cases were those with thyroid compressing symptoms, toxic goiter, Graves' disease, or abnormal laryngoscopy. Cases with asymptomatic goiter or surgeries for a thyroid nodule were classified as incidental. Among 1082 patients with differentiated thyroid cancer, 32% of males and 38% of females presented with symptomatic thyroid disease (p=0.06). A similar rate of presentation of advanced thyroid cancer (T3/4) was seen with male and female patients (n=70, 47% vs. n=79, 53%). Females exhibited a higher prevalence of low-risk relapse cancers according to American Thyroid Association stratification (66.3% vs. 50.4%), whereas males exhibited a higher prevalence of high-risk relapse cancers compared to females (27.3% vs. 15.3%, p<0.001). Regression showed symptoms were associated with more advanced T stage (OR=1.62, p=0.02). Symptomatic presentation was similar between males and females, but symptomatic presentation was associated with larger cancers. This study highlights comparable rates of symptomatic detection between males and females with DTCs and symptomatic presentations were responsible for less than 40% of presentations.

Association between provegetarian food patterns and micronutrient adequacy in preschoolers: the SENDO project.

Adherence to a healthful provegetarian food pattern is associated with improved nutritional adequacy in preschoolers, while following an unhealthful pattern is detrimental to micronutrient adequacy. These results suggest that moderate reductions in animal food consumption within a healthy diet may not compromise micronutrient adequacy in young children. Further research is needed to explore the impact of diets reduced in animal food intake on the health of children. • There's a notable trend towards plant-based diets due to health and sustainability concerns. • Research links plant-based diets in adults with lower risks of obesity, cardiovascular disease, and cancer. •A new study examines how different versions of a provegetarian food pattern affect micronutrient adequacy in children, using a moderate andstepwise approach. •Following a healthful provegetarian food pattern enhances nutritional adequacy in preschoolers, whereas an unhealthful pattern negativelyimpacts micronutrient adequacy.

Plant-based diets and urological health.

Plant-based diets have grown in popularity owing to multiple health and environmental benefits. Some evidence suggests that plant-based diets are associated with benefits for urological health. In genitourinary oncology, most research has focused on prostate cancer. Clinical trial results suggest a favourable influence of healthy lifestyle modifications including plant-based diets before and after prostate cancer treatment. Epidemiological evidence shows that a diet higher in plant-based and lower in animal-based food is associated with a lower risk of aggressive prostate cancer and better quality-of-life scores than a diet with less plant-based and more animal-based food. Studies on bladder and kidney cancer are scarce, but limited data suggest that vegetarian or plant-forward dietary patterns (increased consumption of fruits and vegetables and minimizing meat) are associated with a lower risk of development of these cancers than dietary patterns with fewer fruits and vegetables and more meat. With respect to benign urological conditions, epidemiological studies suggest that plant-based dietary patterns are associated with a lower risk of benign prostatic hyperplasia and urinary tract infections than non-plant-based dietary patterns. Compared with diets high in animal-based foods and low in plant-based foods, a substantial body of epidemiological evidence also suggests that increased consumption of healthy plant-based food is associated with a lower risk of erectile dysfunction. Plant-based dietary patterns that are high in fruits and vegetables with normal calcium intake, while limiting animal protein and salt, are associated with a lower risk of kidney stone development than dietary patterns that do not follow these parameters. Overall, increasing consumption of plant-based foods and reducing intake of animal-based foods has favourable associations with multiple urological conditions.

Assessing radioiodine therapy long-term outcomes in differentiated thyroid cancer using nomograms.

This study explored the role of radioiodine therapy (RAI) in low-risk thyroid cancer patients and examined the disease-specific survival (DSS) rates in a large cohort of differentiated thyroid cancer patients (DTC). We obtained patient data from SEER database. Patients who underwent total thyroidectomy were included and categorized into three groups based on histology: classical papillary thyroid carcinoma (C-PTC), follicular type variant carcinoma (FV-PTC), and follicular thyroid cancer (FTC). Patients with distant metastasis, tumor size ≥ 200mm, chemotherapy, or any type of radiation other than RAI were also excluded. A nomogram was developed and tested for discrimination and calibration. In total, 96,532 thyroid cancer cases were examined, including 59,460 C-PTC, 31,583 FV-PTC, and 5,489 FTC cases. Age > 65years and male sex were correlated with lower survival rates across the subtypes. In addition, extrathyroidal extension had a worse survival effect in patients with FTC. DSS rates were compared between patients who received RAI and those who did not, with a 3% difference in C-PTC (94% vs. 91%, p < 0.001), 2% in FV-PTC (92% vs. 90%, p < 0.001), and 1% in FTC (89% vs. 88%, p = 0.084) at 15years. The nomograms for long-term DSS showed high discriminatory abilities with C-indices of 0.815, 0.805, and 0.781 for C-PTC, FV-PTC, and FTC, respectively. The developed nomogram can be used in the treatment plan for patients with DTC. Our study emphasizes the prognostic factors for DTC and highlights the need for personalized treatment plans based on individual risk profiles.

6913 Clinical Prognosis in Patients with Thyroid Nodules Expressing PPAR-Gamma Gene Fusion on Thyroid FNA Cytology

Abstract Disclosure: R. Hammoudeh: None. E. Morariu: None. A. Wald: Other; Self; Technical consultant to Sonic Healthcare USA.. W.R. Doerfler: None. Y. Linwah: None. M. Nikiforova: Owner/Co-Owner; Self; Owner of intellectual property related to ThyroSeq, receive royalties through the University of Pittsburgh; consultants for Sonic Healthcare USA. Y.E. Nikiforov: Owner/Co-Owner; Self; Owner of intellectual property related to ThyroSeq, receive royalties through the University of Pittsburgh; consultants for Sonic Healthcare USA. Background: PPARG rearrangements, typically PAX8-PPARG, are common genetic alterations in follicular thyroid carcinoma and follicular variant of papillary thyroid carcinoma (FVPTC). Most tumors appear to be indolent, however distant metastasis has been reported. The aim of this study was to determine the prevalence and type of malignancy in a series of thyroid nodules positive for PAX8 rearrangement in thyroid fine-needle aspiration (FNA) samples. We also aimed to evaluate the impact on patient management, prognosis and outcomes. Methods: Thyroid nodules positive for PAX8 fusion on ThyroSeq v2 and v3 genomic classifier testing of FNA samples from May 2008 to February 2022 were identified. Clinical data was obtained by retrospective chart review. Results: Overall, 44 nodules positive for PAX8/PPARG fusion were identified. None of these nodules expressed additional genetic mutations on molecular testing. Surgical pathology was available for 40 patients, which identified 35 (87.5%) malignant, 3 NIFTP (7.5%), and 2 benign (5%) lesions. In the malignant group, FNA cytology revealed 1 (2.8%) benign, 13 (37.1%) AUS/FLUS, 12 (34.2%) suspicious for SFN/FN, 5 (14.3%) suspicious for PTC and 4 were not classified. In the non-malignant group, FNA cytology revealed 2 (40%) benign, 2 (40%) AUS/FLUS, 1 (20%) SFN/FN. With regards to surgical intervention, 30 (75%) patients had total thyroidectomy and 10 (25%) underwent lobectomy, of which 8 were followed by completion thyroidectomy. Among the malignant and non-malignant groups, there was no difference in sex (82.8% vs 100% female, p=1), age (43.6 vs 50.2 years, p=0.2), or tumor size on surgical pathology (3.26 vs 4 cm, p=0.23). In the malignant group, histology showed 30 (85.7%) FVPTC, 2 (5.7%) conventional PTC, 2 (5.7%) follicular carcinoma and 1 (2.9%) solid variant PTC. Of the FVPTC group, 9 had oncocytic cell features, 3 focal solid patterns, and 1 showed focal solid growth and progression to poorly differentiated thyroid carcinoma. Only 1 showed lymphatic invasion, 10 showed angioinvasion. Following the ATA thyroid cancer risk stratification, 23 (65.7%%) had low risk, 9 (25.7%) intermediate risk and 3 (8.6%) high risk. 18 patients in the malignant group underwent RAI ablation. Average follow up for the malignant nodules was 49.7 months (0-170). 1 had suspected recurrence on thyroid ultrasound after a year. No evidence of distant metastasis was documented. Conclusions: The majority of thyroid nodules with PAX8/PPARG rearrangement found on FNA were cancers, predominantly follicular variant PTC, and some were benign or NIFTP. The majority were low risk, but intermediate and high-risk cancers with more aggressive histology, angioinvasion, and poorly differentiated cancer were also identified. While only one recurrence was identified on short follow-up, longer follow-up duration is required for better understanding the behavior of these tumors. Presentation: 6/3/2024

7478 Effects of RAI on Papillary Thyroid Carcinoma with Positive Lymph Nodes

Abstract Disclosure: K.N. Rachmasari: None. A. Osman: None. D. Toro Tobon: None. S.B. Lund: None. D.J. Merlino: None. A.R. Hsu: None. M.M. Ryder: None. Background: In low-risk papillary thyroid cancer (PTC), radioactive iodine (RAI) remnant ablation has shown no impact on disease recurrence rates, which are overall low. The role of adjuvant RAI in intermediate risk disease (i.e. T3, N1) remains unproven with no randomized clinical trials to objectively assess efficacy. Thus, in our institution, its use is highly heterogenous. We retrospectively investigated the effects of adjuvant RAI on recurrence and recurrence free survival (RFS) in patients with PTC and positive cervical lymph nodes (CLN). Methods: We performed a retrospective review of patients who underwent surgery at Mayo Clinic Rochester, MN for PTC between January 2007 and December 2016. Adult patients with Tx-T3 disease according to the 8th edition of American Joint Committee on Cancer (AJCC) were identified. Patients with positive CLN (N1) and a minimum follow up of 36 months were included. Demographics, clinicopathologic characteristics, use of RAI therapy and recurrence were analyzed. Results: A total of 367 patients with PTC, Tx-3, N1, M0 were identified, of which 187 received adjuvant RAI and 180 did not. Most patients were female (63.8%), with a median age of 44 years (IQR 34-54), and a median follow up of 77 months (IQR 58.5-101.5). There were no differences in age, type of surgery, histology, multifocality, and follow up period between the RAI and no RAI subgroups. Adjuvant Thyrogen-stimulated or thyroid hormone withdrawal-based RAI was recommended at the discretion of the treating provider and/or per patient preference. Diagnostic I-123 whole body scans were performed in all patients and mostly demonstrated remnant uptake. The median dose of I-131 was 75 mCi (range 50-100). Recurrence was defined by new occurrence of disease after at least a year of absence of clinical, biochemical, and imaging evidence of disease since initial surgery. Within the entire cohort, 35 (9.5%) developed recurrence with a median time of 41 months (28-59.5). Overall, recurrence rate and RFS were not significantly different between both subgroups (p = 0.2). A subanalysis was performed in patients with clinically detectable nodal disease (n = 161), defined by abnormal cervical lymph node on preoperative neck ultrasound with or without positive fine needle aspiration biopsy. Overall recurrence rates were 17 (10.6%) in this group. There were no differences in recurrence rates and RFS in those that received RAI versus those that did not (p = 0.8). Conclusions: In patients with intermediate risk PTC defined by nodal disease and/or T3 disease, recurrences were not different between patients that did or did not receive adjuvant I-131 therapy postoperatively. A randomized, noninferiority study of adjuvant I-131 compared to no I-131 postoperatively for N1 disease is needed to determine the benefit of near total thyroidectomy and adjuvant I-131 for this cohort. Presentation: 6/3/2024

Association between dietary factors and breast cancer risk: a matched case-control study in Vietnam

BackgroundThe role of diet in breast cancer prevention is controversial and limited in low-middle-income countries (LMICs). This study aimed to investigate the association between different dietary factors and breast cancer risk in Vietnamese women.MethodsThree hundred seventy newly histologically confirmed breast cancer cases and 370 controls matched by 5-year age from September 2019 to March 2020 in Ho Chi Minh City were recorded dietary intake using a validated food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (95% CI) were evaluated using conditional logistic regression and adjusted with potential confounders.ResultsCompared to the lowest quartile of intake, we found that the highest intake of vegetables, fruit, soybean products, coffee, and egg significantly decreased breast cancer risk, including dark green vegetables (OR 0.46, 95% CI 0.27-0.78, ptrend=0.022), legumes (OR 0.19, 95% CI 0.08-0.44, ptrend <0.001), starchy vegetables (OR 0.37, 95% CI 0.21-0.66, ptrend=0.003), other vegetables (OR 0.46, 95% CI 0.28-0.77, ptrend=0.106), fruits (OR 0.44, 95% CI 0.26-0.74, ptrend <0.001), soybean product (OR 0.45, 95% CI 0.24-0.86, ptrend=0.311), coffee (OR 0.47, 95% CI 0.23-0.95, ptrend 0.004), and egg (OR 0.4, 95% CI 0.23-0.71, ptrend=0.002).ConclusionGreater consumption of vegetables, fruit, soybean products, coffee, and eggs is associated with a lower risk of breast cancer. This study provides evidence of breast cancer prevention by increasing the intake of these dietary groups, especially in LMICs.

Physical Health Among Black Immigrants by Region of Birth: A Test of the Racial Context Hypothesis.

We test the Racial Context Hypothesis by examining the association between racial context of origin and five physical health outcomes (self-rated health, activity limitation, functional activity limitation, lifetime hypertension, and lifetime cancer) among U.S.-born Black Americans and Black immigrants in the United States. This cross-sectional study used 2000 through 2018 waves of the National Health Interview Survey (NHIS). Our subsample was limited to adults 18years of age or older who self-identified as Black and selected a distinct global region of birth if not U.S. born (N = 212,269). We employed zero-order logistic regression models to estimate the relationships between each measure of health and racial context by region of birth. Supporting the Racial Context Hypothesis, we found Black immigrants from racially mixed (Mexico, Central America, the Caribbean, South America) and majority-Black contexts (Africa) had lower odds of being in fair or poor self-rated health [aOR 0.786; 0.616; 0.611], reporting any activity limitation [aOR = 0.537; 0.369; 0.678], reporting functional activity limitation [aOR 0.619; 0.425; 0.678], reporting lifetime hypertension diagnosis [aOR 0.596; 0.543; 0.618], and reporting lifetime cancer diagnosis [aOR 0.771; 0.326; 0.641] compared to U.S.-born Black Americans. After controlling for sociodemographic and socioeconomic covariates, Black immigrants from majority-White contexts (Europe) did not significantly differ from U.S.-born Black Americans on these five physical health measures. This study expands our understanding of the "Black immigrant advantage" by showing that Black immigrants from predominantly Black and racially mixed regions rated their health status as poor or fair less often, experienced less activity or functional activity limitations, and had a lower risk of lifetime hypertension and cancer compared to U.S.-born Black Americans. The significant associations persisted even after controlling for sociodemographic and socioeconomic characteristics. Black immigrant health is not homogenous, and the racial context of origin Black immigrants come from has an association with their health outcomes.

Comparative analysis of GLP-1 receptor agonists versus metformin on cancer outcomes in patients with polycystic ovarian syndrome: A real-world multi-center cohort study in the United States.

402 Background: To compare the effects of GLP-1 receptor agonists (GLP1RA) versus metformin on incident cancer outcomes in the female polycystic ovarian syndrome (PCOS) population. Methods: This retrospective cohort study utilized electronic health records from over 50 U.S. healthcare organizations (TriNetX). The baseline cohort comprised females aged ≥ 18 with ≥ two prescriptions for GLP1 RAor metformin following a diagnosis of PCOS, between May 1, 2005 (first GLP1 RA approval date), and December 31, 2021. All cancer types were identified using ICD-10 codes. The index date was the initiation of GLP1RA or metformin. We performed a 1:1 propensity score matched based on demographics, comorbidities, socioeconomic factors, healthcare utilization, and biomarkers (HbA1c, LDL, HDL, triglycerides, and cholesterol), insulin use and PCOS medications before index date. Analysis was performed with intention-to-treat approach. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the comparison groups were calculated by the Cox regression model. Patients were followed and censored upon meeting any of the following criteria: development of an outcome, the study end date of May 19, 2024, or loss to follow-up, whichever occurred first. Results: A total of 8,223 pairs of GLP1RA initiators and metformin initiators were included. Compared to metformin, GLP1RA was associated with a lower risk of incident colorectal cancer (HR 0.35, 95% CI 0.22-0.57) and breast cancer (HR 0.55, 95% CI 0.39-0.78). There were no significant differences in risk between the GLP1RA group and metformin group for endometrial (HR 0.82, 95% CI 0.49-1.37), cervical (HR 1.17, 95% CI 0.64-2.12), ovarian (HR 1.09, 95% CI 0.56-2.11), respiratory (HR 0.32, 95% CI 0.17-0.60), skin (HR 0.51, 95% CI 0.37-0.69), kidney cancer(HR 0.99, 95% CI 0.33-3.06), thyroid cancer (HR 1.37, 95% CI 0.88-2.13), other endocrine (HR 0.81, 95% CI 0.15- 0.44), leukemia and lymphoma (HR 1.03, 95% CI 0.91-1.16), brain (HR 0.97, 95% CI 0.24-3.96), pancreatic cancer(HR 0.50, 95% CI 0.16-1.55), esophageal cancer (HR 1.99, 95% CI 0.24-16.18), stomach cancer (HR 0.33, 95% CI 0.07-1.47), and intrahepatic cancer (HR 0.89, 95% CI 0.40-1.99). Conclusions: GLP-1 receptor agonists were associated with a lower risk of colorectal and breast cancer compared to metformin in females with PCOS, with no significant differences in risk for other cancer types.Further investigation is necessary to verify the underlying therapeutic mechanisms.

Sexual Health and Quality of Life in Patients With Low-Risk Early-Stage Cervical Cancer: Results From GCIG/CCTG CX.5/SHAPE Trial Comparing Simple Versus Radical Hysterectomy.

Simple hysterectomy and pelvic node assessment (SHAPE) is a phase III randomized trial (ClinicalTrials.gov identifier: NCT01658930) reporting noninferiority of simple compared with radical hysterectomy for oncologic outcomes in low-risk cervical cancer. This study presents secondary outcomes of sexual health and quality of life (QOL) of the SHAPE trial. Participants were randomly assigned to receive either radical or simple hysterectomy. Sexual health was assessed up to 36 months postoperatively using the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised and QOL using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Cervical Cancer-Specific Module (QLQ-CX24) questionnaires. Among participants with at least one QOL measure, clinical and pathologic characteristics were balanced and with no differences in preoperative baseline scores for sexual health or QOL between groups. FSFI total score met the cutoff for dysfunction up to 6 months (P = .02) in the radical hysterectomy group. Group differences favored simple hysterectomy for FSFI subscales: desire and arousal at 3 months (P ≤ .001) and pain and lubrication up to 12 months (P ≤ .018). Both groups met the cutoff for sexual distress but was higher in radical hysterectomy at 3 months (P = .018). For QLQ-CX24, symptom experience was significantly better up to 24 months (P = .031) and body image better at 3, 24, and 36 months (P ≤ .01) for simple hysterectomy. Sexual-vaginal functioning was significantly better up to 24 months (P ≤ .022) and more sexual activity up to 36 months (P = .024) in the simple hysterectomy arm. Global health status was significantly higher at 36 months for simple hysterectomy (P = .025). Simple hysterectomy was associated with lower rates of sexual dysfunction than radical hysterectomy, with a lower proportion of women having sustained sexual-vaginal dysfunction. These results further support the benefit of surgical de-escalation for low-risk cervical cancer.

P4.04D.04 Efficiency of the Annual CT Screening Interval for Those at a Lower Risk of Lung Cancer - A CISNET Comparative Modelling Study

P4.04D.04 Efficiency of the Annual CT Screening Interval for Those at a Lower Risk of Lung Cancer - A CISNET Comparative Modelling Study

S2351 GLP-1 RA Use in Patients with T2DM is Associated with Lower Risk of Gastric Cancer: A National Analysis

S2351 GLP-1 RA Use in Patients with T2DM is Associated with Lower Risk of Gastric Cancer: A National Analysis

S727 GLP-1 RA Use in Patients with T2DM is Associated with Lower Risk of Esophageal Cancer: A National Analysis

S727 GLP-1 RA Use in Patients with T2DM is Associated with Lower Risk of Esophageal Cancer: A National Analysis

Association of SGLT2 Inhibitors with Incident Cancer: SGLT2i and 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.

Risk-prediction models in postmenopausal patients with symptoms of suspected ovarian cancer in the UK (ROCkeTS): a multicentre, prospective diagnostic accuracy study

Multiple risk-prediction models are used in clinical practice to triage patients as being at low risk or high risk of ovarian cancer. In the ROCkeTS study, we aimed to identify the best diagnostic test for ovarian cancer in symptomatic patients, through head-to-head comparisons of risk-prediction models, in a real-world setting. Here, we report the results for the postmenopausal cohort. In this multicentre, prospective diagnostic accuracy study, we recruited newly presenting female patients aged 16-90 years with non-specific symptoms and raised CA125 or abnormal ultrasound results (or both) who had been referred via rapid access, elective clinics, or emergency presentations from 23 hospitals in the UK. Patients with normal CA125 and simple ovarian cysts of smaller than 5 cm in diameter, active non-ovarian malignancy, or previous ovarian malignancy, or those who were pregnant or declined a transvaginal scan, were ineligible. In this analysis, only postmenopausal participants were included. Participants completed a symptom questionnaire, gave a blood sample, and had transabdominal and transvaginal ultrasounds performed by International Ovarian Tumour Analysis consortium (IOTA)-certified sonographers. Index tests were Risk of Malignancy 1 (RMI1) at a threshold of 200, Risk of Malignancy Algorithm (ROMA) at multiple thresholds, IOTA Assessment of Different Neoplasias in the Adnexa (ADNEX) at thresholds of 3% and 10%, IOTA SRRisk model at thresholds of 3% and 10%, IOTA Simple Rules (malignant vs benign, or inconclusive), and CA125 at 35 IU/mL. In a post-hoc analysis, the Ovarian Adnexal and Reporting Data System (ORADS) at 10% was derived from IOTA ultrasound variables using established methods since ORADS was described after completion of recruitment. Index tests were conducted by study staff masked to the results of the reference standard. The comparator was RMI1 at the 250 threshold (the current UK National Health Service standard of care). The reference standard was surgical or biopsy tissue histology or cytology within 3 months, or a self-reported diagnosis of ovarian cancer at 12 month follow-up. The primary outcome was diagnostic accuracy at predicting primary invasive ovarian cancer versus benign or normal histology, assessed by analysing the sensitivity, specificity, C-index, area under receiver operating characteristic curve, positive and negative predictive values, and calibration plots in participants with conclusive reference standard results and available index test data. This study is registered with the International Standard Randomised Controlled Trial Number registry (ISRCTN17160843). Between July 13, 2015, and Nov 30, 2018, 1242 postmenopausal patients were recruited, of whom 215 (17%) had primary ovarian cancer. 166 participants had missing, inconclusive, or other reference standard results; therefore, data from a maximum of 1076 participants were used to assess the index tests for the primary outcome. Compared with RMI1 at 250 (sensitivity 82·9% [95% CI 76·7 to 88·0], specificity 87·4% [84·9 to 89·6]), IOTA ADNEX at 10% was more sensitive (difference of -13·9% [-20·2 to -7·6], p<0·0001) but less specific (difference of 28·5% [24·7 to 32·3], p<0·0001). ROMA at 29·9 had similar sensitivity (difference of -3·6% [-9·1 to 1·9], p=0·24) but lower specificity (difference of 5·2% [2·5 to 8·0], p=0·0001). RMI1 at 200 had similar sensitivity (difference of -2·1% [-4·7 to 0·5], p=0·13) but lower specificity (difference of 3·0% [1·7 to 4·3], p<0·0001). IOTA SRRisk model at 10% had similar sensitivity (difference of -4·3% [-11·0 to -2·3], p=0·23) but lower specificity (difference of 16·2% [12·6 to 19·8], p<0·0001). IOTA Simple Rules had similar sensitivity (difference of -1·6% [-9·3 to 6·2], p=0·82) and specificity (difference of -2·2% [-5·1 to 0·6], p=0·14). CA125 at 35 IU/mL had similar sensitivity (difference of -2·1% [-6·6 to 2·3], p=0·42) but higher specificity (difference of 6·7% [4·3 to 9·1], p<0·0001). In a post-hoc analysis, when compared with RMI1 at 250, ORADS achieved similar sensitivity (difference of -2·1%, 95% CI -8·6 to 4·3, p=0·60) and lower specificity (difference of 10·2%, 95% CI 6·8 to 13·6, p<0·0001). In view of its higher sensitivity than RMI1 at 250, despite some loss in specificity, we recommend that IOTA ADNEX at 10% should be considered as the new standard-of-care diagnostic in ovarian cancer for postmenopausal patients. UK National Institute of Heath Research.

Intermittent Fasting on Cancer: An Update

Intermittent fasting (IF) has garnered considerable interest as a dietary intervention with potential therapeutic benefits for various medical conditions, particularly cancer. This review provides a comprehensive update on the effects of IF on cancer, emphasizing its impact on metabolic, hormonal, and cellular mechanisms. IF has been shown to improve glycemic control and reduce liver enzyme levels in patients with non-alcoholic fatty liver disease (NAFLD), suggesting a reduction in liver cancer risk. It can significantly reduce tumor growth and enhance apoptosis in breast cancer by lowering insulin-like growth factor 1 (IGF-1) levels. In patients with polycystic ovary syndrome (PCOS), IF offers superior metabolic and hormonal regulation, potentially lowering cancer risk. IF mitigates chemotherapy-related toxicities, thereby improving patient quality of life. It modulates metabolic pathways, reduces inflammation, and enhances drug delivery in cancer therapy. Personalized dietary strategies, including IF and ketogenic diets, are crucial in cancer care. IF also benefits liver conditions by reducing inflammation and fibrosis, preventing the progression to hepatocellular carcinoma. In obesity-induced triple-negative breast cancer, IF disrupts critical processes involved in cancer progression. In addition, aligning IF with circadian rhythms has shown promise in treating lung cancer. Patient perspectives reveal that IF is feasible and acceptable, improving treatment adherence and quality of life. Overall, IF represents a multifaceted approach to cancer prevention and therapy. This review advocates for further research to establish standardized guidelines for implementing IF in oncology, aiming to develop more effective and holistic cancer treatment strategies.

Survival After Simple Compared With Radical Hysterectomy for Patients With Early-Stage Cervical Cancer.

To assess the effect on overall survival of simple hysterectomy with lymph node staging compared with radical hysterectomy with lymph node staging for patients with early-stage cervical cancer. We conducted a retrospective cohort study of patients in the National Cancer Database diagnosed with early cervical carcinoma of 2 cm or smaller (stage IA1 with lymphovascular space invasion through IIA1, International Federation of Gynecology and Obstetrics staging) from 2010 to 2019. After 1:1 propensity score matching, we compared patients who underwent simple hysterectomy with lymph node staging and those with radical hysterectomy with lymph node staging. The variables used for matching were age, tumor size, race and ethnicity, lymphovascular space invasion, year of diagnosis, Charlson-Deyo comorbidity score, histology, and surgical approach. The primary outcome was overall survival at the end of follow-up. Secondary outcomes included 30-day readmission rate and 30- and 90-day mortality rates. In total, 4,167 patients met the inclusion criteria, of whom 2,637 patients (63.3%) underwent radical hysterectomy and lymph node staging and 1,530 patients (36.7%) underwent simple hysterectomy and lymph node staging. After propensity score matching, 1,529 patients in each group were included. There was no statistically significant difference in overall survival between patients who underwent simple hysterectomy and those who underwent radical hysterectomy (hazard ratio 1.25, 95% CI, 0.91-1.73, P=.17). Subgroup analysis by histology, lymphovascular space invasion, tumor size, and surgical approach did not reveal statistically significant differences in overall survival according to hysterectomy type. The hysterectomy groups also did not significantly differ in 30-day readmission rate (4.6% vs 4.2%, P=.73), 30-day mortality rate (0.1% vs 0%, P=.14), or 90-day mortality rate (0.1% vs 0.1%, P=.93). Patients with low-risk cervical cancer could undergo less radical surgery without a negative effect on their oncologic outcomes.

Statins in the Cause and Prevention of Cancer: Confounding by Indication and Mediation by Rhabdomyolysis and Phosphate Toxicity.

Statins are drugs used in cardiovascular pharmacotherapy to decrease hypercholesterolemia and lower the risk of atherosclerosis. Statins also increase the risk of rhabdomyolysis, which is often minimized in comparison with large relative risk reductions of cardiovascular disease reported in clinical trials. By contrast, absolute risk reductions of cardiovascular disease are often clinically insignificant and unreported in statin clinical trials. Additionally, cytotoxic effects of statins inhibit cancer cell proliferation and reduce cancer risk, but other studies found that statins are carcinogenic. Due to an inverse association between incidence of cancer and atherosclerosis, the indication to prescribe statins likely biases the association of statins with cancer prevention. Dietary patterns associated with atherosclerosis and cancer contain inverse amounts of cholesterol and phosphate, an essential mineral that stimulates tumorigenesis. Accordingly, lower cancer risk is associated with high dietary cholesterol intake and increased risk of atherosclerosis. Furthermore, serum is exposed to excessive inorganic phosphate that could increase cancer risk as rhabdomyolysis induced by statins releases phosphate from skeletal muscle breakdown. Increased risk of comorbid conditions associated with statins may share the mediating factor of phosphate toxicity. More research is warranted on statins in the cause and prevention of cancer.

Risk of Esophageal and Gastric Cancer in Patients with Type 2 Diabetes Receiving Glucagon-like Peptide-1 Receptor Agonists (GLP-1 RAs): A National Analysis.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are becoming more popular in managing type 2 diabetes mellitus (T2DM). Concerns linger over potential links to malignancies like pancreatic and thyroid cancers, requiring more research to clarify their safety profiles. Additionally, evidence suggests GLP-1 RAs may lower colorectal and pancreatic cancer risk, especially in obese and overweight individuals, indicating a protective effect beyond weight loss. Current studies leave a gap in comprehensively understanding cancer risks associated with GLP-1 RAs, which prompts further research to enhance our understanding of their overall safety. We queried the US Collaborative Network (63 health care organizations) of the TriNetX research database. Patients with T2DM were identified and divided into two cohorts: patients on GLP-1 RAs and patients not on GLP-1 RAs. We excluded tobacco use and alcohol use disorders, obese patients with a body mass index (BMI) of >25 kg/m2, and those with a family history of gastrointestinal malignancy, infectious mononucleosis, chronic gastritis, pernicious anemia, helicobacter pylori infection, or gastroesophageal reflux disease (GERD). We used a 1:1 propensity score matching (PSM) model using patients' baseline characteristics, medications, labs, and genetics. We compared the rate of gastric cancer and esophageal cancer at the seven-year mark. A total of 2,748,431 patients with T2DM were identified. Of those, 6% (n = 167,077) were on a GLP-1 RA and 94% (n = 2,581,354) were not on a GLP-1 RA. After PSM, both cohorts included 146,277 patients. Patients with T2DM who were on a GLP-1 RA, compared to those who were not, had a statistically significant lower risk of both gastric cancer (0.05% vs. 0.13%, p < 0.0001) and esophageal cancer (0.04% vs. 0.13%, p < 0.0001) at the seven-year mark. The use of GLP-1 RAs in patients with T2DM does not significantly increase the risk of gastric or esophageal cancer. This finding supports the continued use of GLP-1 analogues as a therapeutic option in managing T2DM, considering their well-established benefits and low risk of complications. Based on the study results, these medications may even have a protective effect against these malignancies.