Risk Of Primary Cancer Research Articles

Updated Standardized Definitions for Efficacy End Points (STEEP) in Adjuvant Breast Cancer Clinical Trials: STEEP Version 2.0.

The Standardized Definitions for Efficacy End Points (STEEP) criteria, established in 2007, provide standardized definitions of adjuvant breast cancer clinical trial end points. Given the evolution of breast cancer clinical trials and improvements in outcomes, a panel of experts reviewed the STEEP criteria to determine whether modifications are needed. We conducted systematic searches of ClinicalTrials.gov for adjuvant systemic and local-regional therapy trials for breast cancer to investigate if the primary end points reported met STEEP criteria. On the basis of common STEEP deviations, we performed a series of simulations to evaluate the effect of excluding non-breast cancer deaths and new nonbreast primary cancers from the invasive disease-free survival end point. Among 11 phase III breast cancer trials with primary efficacy end points, three had primary end points that followed STEEP criteria, four used STEEP definitions but not the corresponding end point names, and four used end points that were not included in the original STEEP manuscript. Simulation modeling demonstrated that inclusion of second nonbreast primary cancer can increase the probability of incorrect inferences, can decrease power to detect clinically relevant efficacy effects, and may mask differences in recurrence rates, especially when recurrence rates are low. We recommend an additional end point, invasive breast cancer-free survival, which includes all invasive disease-free survival events except second nonbreast primary cancers. This end point should be considered for trials in which the toxicities of agents are well-known and where the risk of second primary cancer is small. Additionally, we provide end point recommendations for local therapy trials, low-risk populations, noninferiority trials, and trials incorporating patient-reported outcomes.

Total cholesterol, alanine aminotransferase and the risk of primary liver cancer: A population-based prospective study.

Previous studies have shown that serum total cholesterol (TC) and serum alanine aminotransferase (ALT) are associated with liver cancer risk. However, the common contribution of TC and normal-high ALT to primary liver cancer (PLC) has not been reported. We aim to assess the separate and joint effect of low TC level and normal-high ALT level on the risk of PLC, a large prospective cohort was conducted in our study.The participants were divided into 4 groups via the cross-matching method according to TC [low level (−)/non-low level (+)] and ALT [normal level (−)/normal-high level(+)] status, and using the lower quartile value of TC and the upper quartile value of ALT as a threshold, respectively. Incident PLC was confirmed by review of medical records. Cox proportional hazards regression models and interactive additive models were used to evaluate whether the joint effect of low TC level and normal-high ALT level is associated with the risk of PLC.During 1,248,895 person-years follow-up, 298 participants were diagnosed with PLC among 114,972 subjects. In male population, TC < 4.24 mmol/L was group “TC (−)”; TC ≥ 4.24 mmol/L was group “TC (+)”; ALT < 23 U/L was group “ALT (−)”: 33 U/L ≥ ALT ≥ 23 U/L was group “ALT (+)”. Compared with the group “TC (+)”, group “ALT (−)”, respectively, the adjusted hazard ratio (HR) and 95% confidence interval (95%CI) for PLC risk was 1.74 (1.36–2.25) in group “TC (−)” and 1.49 (1.15–1.94) in group “ALT (+)”. In combinatorial analysis, compared with group “TC (+) and ALT (−)”, the significant increased risk of PLC were observed in group “TC (+) and ALT (+)” (HR = 1.41; 95% confidence intervals [CI]: 1.02–1.95), group “TC (−) and ALT (−)” (HR = 1.67; 95%CI: 1.24–2.27) and group “TC (−) and ALT (+)” (HR = 2.72; 95%CI: 1.81–4.09), respectively. However, no statistical significance was found among female.The separate and joint effect of low TC level and normal-high ALT level was observed for PLC risk in males. When combined, individuals with coexistence of low TC level and normal-high ALT level significantly increase the risk of PLC.

Increased risk of secondary lung cancer in patients with tuberculosis: A nationwide, population-based cohort study.

BackgroundTuberculosis (TB) presents a global threat in the world and the lung is the frequent site of metastatic focus. A previous study demonstrated that TB might increase primary lung cancer risk by two-fold for more than 20 years after the TB diagnosis. However, no large-scale study has evaluated the risk of TB and secondary lung cancer. Thus, we evaluated the risk of secondary lung cancer in patients with or without tuberculosis (TB) using a nationwide population-based dataset.MethodsIn a cohort study of 1,936,512 individuals, we selected 6934 patients among patients with primary cancer and TB infection, based on the International Classification of Disease (ICD-p-CM) codes 010–011 from 2000 to 2015. The control cohort comprised 13,868 randomly selected, propensity-matched patients (by age, gender, and index date) without TB exposure. Using this adjusted date, a possible association between TB and the risk of developing secondary lung cancer was estimated using a Cox proportional hazards regression model.ResultsDuring the follow-up period, secondary lung cancer was diagnosed in 761 (10.97%) patients with TB and 1263 (9.11%) patients without TB. After adjusting for covariates, the risk of secondary lung cancer was 1.67 times greater among primary cancer in the cohort with TB than in the cohort without TB. Stratification revealed that every comorbidity (including diabetes, hypertension, cirrhosis, congestive heart failure, cardiovascular accident, chronic kidney disease, chronic obstructive pulmonary disease) significantly increased the risk of secondary lung cancer when comparing the TB cohort with the non-TB cohort. Moreover, the primary cancer types (including head and neck, colorectal cancer, soft tissue sarcoma, breast, kidney, and thyroid cancer) had a more significant risk of becoming secondary lung cancer.ConclusionA significant association exists between TB and the subsequent risk for metastasis among primary cancers and comorbidities. Therefore, TB patients should be evaluated for the subsequent risk of secondary lung cancer.

Examining the gut-liver axis in liver cancer using organoid models.

The World Health Organization predicts that by 2030 liver cancer will cause 1 million deaths annually, thus becoming the third most lethal cancer worldwide. Hepatocellular carcinoma and cholangiocarcinoma are the two major primary cancer subtypes involving the liver. Both are often diagnosed late, and hence response to treatment and survival are poor. It is therefore of utmost importance to understand the mechanisms by which liver cancers initiate and progress. The causes of primary liver cancer are diverse, resulting primarily from obesity, chronic alcohol abuse or viral hepatitis. Importantly, both alcohol and high fat diet can promote intestinal permeability, enabling microbial translocation from the gut into the liver. As a result, these microbial antigens and metabolites exacerbate hepatic inflammation and fibrosis, increasing the risk of primary liver cancer. Organoids are primary, three-dimensional, stem cell derived liver models that can recapitulate many of the disease phenotypes observed in vivo. This review aims to summarize the advantages of organoid culture to examine the gut-liver axis with respect to cancer initiation and progression. In particular, the use of gut and liver organoid mono- and co-cultures together and with immune cell populations to best recapitulate disease mechanisms and develop therapeutic interventions.

Smoking, Radiation Therapy, and Contralateral Breast Cancer Risk in Young Women.

Evidence is mounting that cigarette smoking contributes to second primary contralateral breast cancer (CBC) risk. Whether radiation therapy (RT) interacts with smoking to modify this risk is unknown. In this multicenter, individually matched, case-control study, we examined the association between RT, smoking, and CBC risk. The study included 1521 CBC cases and 2212 controls with unilateral breast cancer, all diagnosed with first invasive breast cancer between 1985 and 2008 aged younger than 55 years. Absorbed radiation doses to contralateral breast regions were estimated with thermoluminescent dosimeters in tissue-equivalent anthropomorphic phantoms, and smoking history was collected by interview. Rate ratios (RRs) and 95% confidence intervals (CIs) for CBC risk were estimated by multivariable conditional logistic regression. There was no interaction between any measure of smoking with RT to increase CBC risk (eg, the interaction of continuous RT dose with smoking at first breast cancer diagnosis [ever/never]: RR = 1.00, 95% CI = 0.89 to 1.14; continuous RT dose with years smoked: RR = 1.00, 95% CI = 0.99 to 1.01; and continuous RT dose with lifetime pack-years: RR = 1.00, 95% CI = 0.99 to 1.01). There was no evidence that RT further increased CBC risk in young women with first primary breast cancer who were current smokers or had smoking history.

Serum Levels of Androgens, Estrogens, and Sex Hormone Binding Globulin and Risk of Primary Gastric Cancer in Chinese Men: A Nested Case-Control Study.

Gastric cancer shows a strong male predominance, and sex steroid hormones have been hypothesized to explain this sex disparity. Previous studies examining the associations between sex hormones and sex hormone binding globulin (SHBG) and risk of gastric cancer come primarily from western populations and additional studies in diverse populations will help us better understand the association. We performed a nested case-control study in Linxian Nutrition Intervention Trials cohorts to evaluate the associations among Chinese men, where we had sufficient cases to perform a well-powered study. Using radioimmunoassays and immunoassays, we quantitated androgens, estrogens, and SHBG in baseline serum from 328 men that developed noncardia gastric cancer and matched controls. We used multivariable unconditional logistic regression to calculate ORs and 95% confidence intervals (CI) and explored interactions with body mass index (BMI), age, alcohol drinking, smoking, and follow-up time. Subjects with SHBG in the highest quartile, as compared with those in the lowest quartile, had a significantly increased risk of gastric cancer (OR = 1.87; 95% CI, 1.01-3.44). We found some evidence for associations of sex steroid hormones in men with lower BMI. Our study found a novel association suggesting that higher serum concentrations of SHBG may be associated with risk of gastric cancer in men. We found no overall associations with sex hormones themselves, but future studies should expand the scope of these studies to include women and further explore whether BMI modifies a potential association. PREVENTION RELEVANCE: It was the first study to investigate the association of gastric cancer with prediagnostic sex steroid hormones and SHBG in an Asian male population. Although there were no overall associations for sex steroid hormone concentrations, higher concentrations of SHBG was associated with increased risk of noncardia gastric cancer.

Advances in the study of occult malignant tumor-related pyogenic liver abscesses in the digestive system

Pyogenic liver abscess (PLA) accompanied by occult malignant tumors is a rare kind of life-threatening disease. Studies have shown that it can predict the occurrence of cancer, especially hepatobiliary and colorectal cancer. The risk of combined occult primary liver cancer, cholangiocarcinoma, and gastrointestinal cancer is high in PLA patients. Malignant tumor-related PLA lacks specific symptoms and signs. The iodine concentration ratio between the energy spectrum CT lesions and normal liver tissue is of certain value in the differentiation of liver cancer and liver abscess. Computed tomography colonography has a dual role. It can screen patients with PLA for occult colorectal cancer and determine the treatment response of abscess lesions. Klebsiella pneumoniae and Escherichia coli is the main microorganism of PLA related to colorectal cancer, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma. PLA treatment related to hepatobiliary malignant tumor has high complications and mortality, and poor prognosis. Most occult colorectal cancers are in the early stage, and their early detection and prognosis are better than those of PLA patients combined with hepatobiliary malignancies.

Tobacco Smoking and Risk of Second Primary Lung Cancer

IntroductionLung cancer survivors are at high risk of developing a second primary lung cancer (SPLC). However, SPLC risk factors have not been established and the impact of tobacco smoking remains controversial. We examined the risk factors for SPLC across multiple epidemiologic cohorts and evaluated the impact of smoking cessation on reducing SPLC risk. MethodsWe analyzed data from 7059 participants in the Multiethnic Cohort (MEC) diagnosed with an initial primary lung cancer (IPLC) between 1993 and 2017. Cause-specific proportional hazards models estimated SPLC risk. We conducted validation studies using the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N = 3423 IPLC cases) and European Prospective Investigation into Cancer and Nutrition (N = 4731 IPLC cases) cohorts and pooled the SPLC risk estimates using random effects meta-analysis. ResultsOverall, 163 MEC cases (2.3%) developed SPLC. Smoking pack-years (hazard ratio [HR] = 1.18 per 10 pack-years, p < 0.001) and smoking intensity (HR = 1.30 per 10 cigarettes per day, p < 0.001) were significantly associated with increased SPLC risk. Individuals who met the 2013 U.S. Preventive Services Task Force’s screening criteria at IPLC diagnosis also had an increased SPLC risk (HR = 1.92; p < 0.001). Validation studies with the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and European Prospective Investigation into Cancer and Nutrition revealed consistent results. Meta-analysis yielded pooled HRs of 1.16 per 10 pack-years (pmeta < 0.001), 1.25 per 10 cigarettes per day (pmeta < 0.001), and 1.99 (pmeta < 0.001) for meeting the U.S. Preventive Services Task Force’s criteria. In MEC, smoking cessation after IPLC diagnosis was associated with an 83% reduction in SPLC risk (HR = 0.17; p < 0.001). ConclusionsTobacco smoking is a risk factor for SPLC. Smoking cessation may reduce the risk of SPLC. Additional strategies for SPLC surveillance and screening are warranted.

Magnesium intake is associated with a reduced risk of incident liver cancer, based on an analysis of the NIH-American Association of Retired Persons (NIH-AARP) Diet and Health Study prospective cohort

Liver cancer incidence and mortality are escalating globally. Magnesium intake has been studied extensively in nonmalignant liver pathology, but the association between dietary intake of magnesium and primary liver malignancy has not been previously evaluated. We aimed to determine the association between total magnesium intake and primary liver cancer risk. Using the NIH-American Association of Retired Persons (NIH-AARP) Diet and Health Study prospective cohort, we estimated the association between magnesium intake and the risk of incident primary liver cancer using Cox proportional hazard modeling adjusted for relevant confounders. Comprehensive stratified and sensitivity analyses were performed. During 6.4 million person-years of follow-up time, 1067 primary liver cancers occurred in 536,359 participants. Higher magnesium intake was independently associated with a lower risk of liver cancer (P-trend=0.005), with intakes in the highest compared with lowest quartile associated with 35% lower risk (HR: 0.65; 95% CI: 0.48, 0.87). The dose-related inverse association was more pronounced in moderate and heavy alcohol users (HR: 0.54; 95% CI: 0.35, 0.82; P-trend=0.006), and this interaction was statistically significant (P-interaction=0.04). Based on a prospective cohort analysis, we demonstrated that magnesium intake is associated with a lower risk of primary liver cancer, which was more pronounced among moderate and heavy alcohol users. Robust experimental and mechanistic data provide a biological basis to support these findings.

ES24.02 The Rationale for FDA (and EMA) Regulatory Review of Tobacco Use in Clinical Trials

ES24.02 The Rationale for FDA (and EMA) Regulatory Review of Tobacco Use in Clinical Trials

The Risk of Primary Uterine and Cervical Cancer After Hysteropexy

The aim of the study was to determine the rate of subsequent uterine/cervical cancer after hysteropexy compared with hysterectomy with apical prolapse repair. The study used a retrospective cohort of women with uterovaginal prolapse using the Cerner Health Facts database between 2010 and 2018. We identified sacrospinous or uterosacral ligament suspensions or sacral colpopexy/hysteropexy and excluded those with previous hysterectomy. We used the International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes for endometrial cancer/hyperplasia and cervical cancer and then reviewed each case, excluding those whose cancer existed at time of prolapse repair. Given that 0 cancer cases were identified, we used Wilson, Jeffreys, Agresti-Coull, Clopper-Pearson, and Rule of 3 to define 95% confidence intervals to estimate the highest possible rate of cancer in each cohort. A total of 8,927 patients underwent apical prolapse surgery. Of 4,510 with uterovaginal prolapse, 755 (16.7%) underwent hysteropexy. Seventy one with hysterectomy and 5 with hysteropexy had codes for subsequent gynecologic cancer but were excluded on further review. This left 0 gynecologic cancer cases with the largest 95% confidence interval of 0%-0.61% for hysteropexy versus 0%-0.13% for hysterectomy (P > 0.05). The hysteropexy cohort was older (62.6 years vs 57.3 years, P < 0.0001), more likely to have public insurance (51.0% vs 37.9%, P < 0.0001), and less likely to smoke (4.5% vs 7.6%, P = 0.0026). Median follow-up was longer after hysteropexy (1,480 days vs 1,164 days, P < 0.0009). We can say with 95% certainty that uterine or cervical cancer will develop after hysteropexy in fewer than 0.61% of women, which was not different if hysterectomy was performed. This should be included in preoperative counseling for hysteropexy. Studying longer follow-up after hysteropexy may capture more cases of subsequent cancer development.

Race, ethnicity and risk of second primary contralateral breast cancer in the United States.

Breast cancer survivors have a high risk of a second primary contralateral breast cancer (CBC), but there are few studies of CBC risk in racial/ethnic minority populations. We examined whether the incidence and risk factors for CBC differed by race/ethnicity in the United States. Women with a first invasive Stage I-IIB breast cancer diagnosis at ages 20-74 years between 2000 and 2015 in the Surveillance, Epidemiology, and End Results Program (SEER) 18 registries were followed through 2016 for a diagnosis of invasive CBC ≥1 year after the first breast cancer diagnosis. We used cause-specific Cox proportional hazards models to test the association between race/ethnicity and CBC, adjusting for age, hormone receptor status, radiation therapy, chemotherapy and stage at first diagnosis, and evaluated the impact of contralateral prophylactic mastectomy, socioeconomic status, and insurance status on the association. After a median follow-up of 5.9 years, 9247 women (2.0%) were diagnosed with CBC. Relative to non-Hispanic (NH) White women, CBC risk was increased in NH Black women (hazard ratio = 1.44, 95% CI 1.35-1.54) and Hispanic women (1.11, 95% CI 1.02-1.20), with the largest differences among women diagnosed at younger ages. Adjustment for contralateral prophylactic mastectomy, socioeconomic status and health insurance did not explain the associations. Therefore, non-Hispanic Black and Hispanic women have an increased risk of CBC that is not explained by clinical or socioeconomic factors collected in SEER. Large studies of diverse breast cancer survivors with detailed data on treatment delivery and adherence are needed to inform interventions to reduce this disparity.

Expression of aquaporins 3 in low grade risk of recurrence primary bladder cancer.

Bladder cancer (BC) is one of the most frequent malignancy of the urinary tract. Recent studies demonstrated the role of aquaporins urothelial tumor cells (AQPs) as potential prognostic factor for tumor progression and invasion. In this study we investigated the AQP3 expression levels inside primary superficial (pTa) low grade bladder cancer, correlating with pathological parameters and clinical outcomes. We retrospectively analyzed tumor samples of 66 patients with diagnosis of superficial urothelial (pTa) bladder cancer between 1997 and 2007. All patients underwent transurethral bladder resection (TURB) and immediate single instillation of mitomycin C. All tumors samples were blindly reviewed by two expert anatomopathologists and only pTa low grade urothelial bladder cancer were included. Cancer recurrence was defined as the detection of bladder lesions during follow-up cystoscopy. AQP3-immunoreactive areas detected at immunohistochemical analysis were classified as AQP3 positive. Of these 60.6% of patients was detected as negative for AQP3 expression. Forty-two patients develop cancer recurrence during follow-up with a mean progression free survival of 16.44 months. The absence of reaction for AQP3 was observed 56% (9/16) tumor grading G1 and 62% (31/50) tumor grading G2. No correlation was observed with sexual gender, grading of tumor differentiation, and recurrence of cancer disease. Kaplan-Meier curves of disease-free survival (DFS) showed a significant separation (p = 0.028) between patients AQP3-positive and AQP3-negative. It was observed a mean DFS of 23.83 and 14.43 months respectively in absence and presence of AQP3 expression. AQP3 expression is related to disease-free interval (DFI) and the absence of AQP3 expression correlates with a late relapse. The expression of AQP3 does not provide a reproducible quantitative aspect. AQP3 are not suitable to forecast tumor cell behavior but they perform a role as regulator for tumor cell homeostasis and for additional therapeutic developments.

Abstract PD2-11: Breast cancer index is a molecular signature of endocrine responsiveness that determines extended endocrine benefit independent of prognostic risk

Abstract Background: For patients with early stage, hormone receptor positive (HR+) breast cancer, extension of endocrine therapy beyond 5 years reduces the ongoing risk of late distant recurrence and new primary breast cancer but is associated with potentially serious toxicities and side effects that can impair quality of life. While risk stratification by clinicopathological factors and prognostic biomarkers is recommended to guide patient selection, predictive biomarkers that are directly informative of therapeutic response are critical for clinical utility. Breast Cancer Index (BCI) is a gene expression-based signature that reports: 1) BCI Prognostic (BCI Score), which combines the Molecular Grade Index (MGI) with the HOXB13/IL17BR (H/I) ratio to provide individualized risk of late (post-5y) distant recurrence, and 2) BCI Predictive (BCI H/I), which predicts benefit from extended endocrine therapy. In this study, BCI and endocrine benefit from 5 vs 2.5y of extended letrozole were examined by comparing the deterministic effects of prognostic risk vs endocrine response in patients treated in the IDEAL trial.Methods: 908 patients with available tumor tissue were included in this pre-specified and blinded analysis, with recurrence-free interval (RFI) as the primary endpoint. Kaplan-Meier and Cox proportional hazards regression were performed using pre-defined assay cut-points. Clinically high prognostic risk was defined as pN+ and ≥pT2; low prognostic risk was defined as pN0 or pN1 and pT1 or G1. Genomic risk was defined by BCI prognostic categories (High vs Low risk). Results: Patients classified with endocrine responsive disease by BCI (H/I)-High status showed a statistically significant benefit from 5 vs 2.5y of letrozole irrespective of clinical risk, whereas those classified as BCI (H/I)-Low did not show benefit in either clinical risk category. Both clinically High and Low risk patients derived a similar magnitude of benefit when stratified as BCI (H/I)-High (12.5% and 15.1%, respectively). Evaluation of BCI (H/I) predictive performance in the context of BCI prognostic risk categories showed similar results. In particular, patients with High Risk/High Likelihood to benefit showed significantly improved outcomes with extended therapy (HR 0.42 [0.20-0.89]; absolute benefit 10.7%; P=0.020), whereas those with High Risk but Low Likelihood to benefit did not show response to extended endocrine therapy (HR 1.05 [0.58-1.88]; absolute benefit -0.7%; P=0.880), despite considerable risk of late distant recurrence (~20%). Conclusion: Results from this study highlight distinct tumor biology underlying recurrence risk vs endocrine responsiveness in HR+ early stage breast cancer. BCI (H/I) as a molecular signature to identify patients with endocrine responsive disease is a key determinant of benefit and improved outcome with extended endocrine therapy. Prediction of endocrine benefit with BCI (H/I) is a more actionable approach vs risk assessment to individualize discontinuation of or continued treatment with prolonged durations of endocrine therapy. Prognostic RiskBCI Predictive NHR (95% CI)P valueClinical RiskHigh Risk: N+/ T2+ (N=353)High BCI(H/I)1620.32 (0.10-0.98)0.035Low BCI(H/I)1911.13 (0.55-2.31)0.742Low Risk: N0 or N1 &amp; T1 or grade 1 (N=404)High BCI(H/I)1910.15 (0.03-0.66)0.004Low BCI(H/I)2130.75 (0.33-1.70)0.484Genomic RiskHigh BCI Score(N=621)High BCI(H/I)3410.42 (0.20-0.89)0.020Low BCI(H/I)2801.05 (0.58-1.88)0.880Low BCI Score(N=227)High BCI(H/I)600.35 (0.04-3.38)0.344Low BCI(H/I)1670.64 (0.22-1.92)0.425 Citation Format: Gerrit-Jan Liefers, Iris Noordhoek, Kai Treuner, Hein Putter, Yi Zhang, Jenna Wong, Elma Meershoek-Klein Kranenbarg, Marjolijn Duijm-de Carpentier, Cornelis JH Van De Velde, Catherine A Schnabel. Breast cancer index is a molecular signature of endocrine responsiveness that determines extended endocrine benefit independent of prognostic risk [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD2-11.

Effect of Follow-Up Surveillance After Curative-Intent Treatment of NSCLC on Detection of New and Recurrent Disease, Retreatment, and Survival: A Systematic Review and Meta-Analysis

IntroductionPatients with NSCLC may be treated with curative intent, yet they remain at high risk of both disease recurrence and second primary lung cancer (SPLC) and increased risk of early death. Guidelines provide recommendations for follow-up, but there is little consensus, and review of available evidence is necessary. The use of a systematic follow-up strategy for the detection of disease recurrence or SPLC after curative-intent treatment of NSCLC may increase the proportion of patients available for retreatment and increase the survival of patients with surveillance detection. MethodsWe performed a systematic review and meta-analysis of prospective studies on follow-up of NSCLC after curative-intent treatment to answer the following three questions: What is the effect of follow-up on detection of recurrence or SPLC? What is the effect of surveillance detection on curative-intent retreatment? What is the survival impact? ResultsRecurrence or SPLC was observed in 17.8% to 71% of patients. Scheduled imaging-detected recurrence in 60% to 100% of cases, yet neither computed tomography–based (OR = 2.31, 95% confidence interval [CI]: 0.27–19.49, p = 0.44) nor positron emission tomography-computed tomography–based follow-up (OR = 1.431, 95% CI: 0.92–2.22, p = 0.12) was statistically superior to standard follow-up strategies. Detection of disease recurrence/SPLC significantly increased the odds of curative-intent retreatment (OR = 4.31; 95% CI: 2.10–8.84, p < 0.0001). Curative-intent retreatment prolonged survival in reported studies. ConclusionsThe early detection of disease recurrence/SPLC may increase the likelihood of curative-intent retreatment and prolong survival. There is a clear need for prospective randomized controlled studies of follow-up to confirm effectiveness of available follow-up modalities.

Genetically Predicted C-Reactive Protein Associated With Postmenopausal Breast Cancer Risk: Interrelation With Estrogen and Cancer Molecular Subtypes Using Mendelian Randomization

BackgroundImmune-related etiologic pathways that influence breast cancer risk are incompletely understood and may be confounded by lifestyles or reverse causality. Using a Mendelian randomization (MR) approach, we investigated the potential causal relationship between genetically elevated C-reactive protein (CRP) concentrations and primary invasive breast cancer risk in postmenopausal women.MethodsWe used individual-level data obtained from 10,179 women, including 537 who developed breast cancer, from the Women’s Health Initiative Database for Genotypes and Phenotypes Study, which consists of five genome-wide association (GWA) studies. We examined 61 GWA single-nucleotide polymorphisms (SNPs) previously associated with CRP. We employed weighted/penalized weighted–medians and MR gene–environment interactions that allow instruments’ invalidity to some extent and attenuate the heterogeneous estimates of outlying SNPs.ResultsIn lifestyle-stratification analyses, genetically elevated CRP decreased risk for breast cancer in exogenous estrogen-only, estrogen + progestin, and past oral contraceptive (OC) users, but only among relatively short-term users (<5 years). Estrogen-only users for ≥5 years had more profound CRP-decreased breast cancer risk in dose–response fashion, whereas past OC users for ≥5 years had CRP-increased cancer risk. Also, genetically predicted CRP was strongly associated with increased risk for hormone-receptor positive or human epidermal growth factor receptor-2 negative breast cancer.ConclusionsOur findings may provide novel evidence on the immune-related molecular pathways linking to breast cancer risk and suggest potential clinical use of CRP to predict the specific cancer subtypes. Our findings suggest potential interventions targeting CRP–inflammatory markers to reduce breast cancer risk.

Second primary malignancies in colorectal cancer patients

The prevalence of second primary malignancies (SPMs) in the western world is continually increasing with the risk of a new primary cancer in patients with previously diagnosed carcinoma at about 20%. The aim of this retrospective analysis is to identify SPMs in colorectal cancer patients in a single-institution cohort, describe the most frequent SPMs in colorectal cancer patients, and discover the time period to occurrence of second primary tumors. We identified 1174 patients diagnosed with colorectal cancer in the period 2003–2013, with follow-up till 31.12.2018, and median follow-up of 10.1 years, (median age 63 years, 724 men). A second primary neoplasm was diagnosed in 234 patients (19.9%). Older age patients, those with early-stage disease and those with no relapse have a higher risk of secondary cancer development. The median time from cancer diagnosis to development of CRC was 8.9 years for breast cancer and 3.4 years for prostate cancer. For the most common cancer diagnosis after primary CRC, the median time to development was 0–5.2 years, depending on the type of malignancy. Patients with a diagnosis of breast, prostate, or kidney cancer, or melanoma should be regularly screened for CRC. CRC patients should also be screened for additional CRC as well as cancers of the breast, prostate, kidney, and bladder. The screening of cancer patients for the most frequent malignancies along with systematic patient education in this field should be the standard of surveillance for colorectal cancer patients.

Fasting Blood Glucose, Cholesterol, and Risk of Primary Liver Cancer: The Kailuan Study.

PurposeThe influence of fasting blood glucose (FBG) and cholesterolemia primary liver cancer (PLC) in China was analyzed via a large prospective cohort study based on a community population, and the combined effects between them were investigated.Materials and MethodsOverall, 98,936 staff from the Kailuan Group who participated in and finished physical examinations between 2006 and 2007 were included in the cohort study. Their medical information was collected and they were followed up after examination. The correlations of serum FBG or total cholesterol (TC) with PLC were analyzed. Then, we categorized all staff into four groups: normal FBG/non-hypocholesterolemia, normal FBG/hypocholesterolemia, elevated FBG/non-hypocholesterolemia, elevated FBG/hypocholesterolemia, and normal FBG/non-hypocholesterolemia was used as a control group. The combined effects of elevated FBG and hypocholesterolemia with PLC were analyzed using the Age-scale Cox proportional hazard regression model.ResultsDuring 1,134,843.68 person-years follow-up, a total of 388 PLC cases occurred. We found the elevated FBG and hypocholesterolemia increase the risk for PLC, respectively. Compared with the non-hypocholesterolemia/normal FBG group, the risk of PLC was significantly increased in the non-hypocholesterolemia/elevated FBG group (hazard artio [HR], 1.19; 95% confidence interval [CI], 0.88 to 1.62) and hypocholesterolemia/normal FBG group (HR, 1.53; 95% CI, 1.19 to 1.97), and in the hypocholesterolemia/elevated FBG group (HR, 3.16; 95% CI, 2.13 to 4.69). And, a significant interaction effect was found of FBG and TC on PLC. All results were independent from the influence of liver disease.ConclusionElevated serum FBG and hypocholesterolemia are risk factors for PLC, especially when combined. Thus, for the prevention and treatment of PLC, serum FBG and TC levels should be investigated.

Long-term risk of primary liver cancers in entecavir versus tenofovir treatment for chronic hepatitis B

It remains controversial whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) is associated with different clinical outcomes for chronic hepatitis B (CHB). This study aimed to compare the long-term risk of ETV versus TDF on hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in CHB patients from a large multi-institutional database in Taiwan. From 2011 to 2018, a total of 21,222 CHB patients receiving ETV or TDF were screened for eligibility. Patients with coinfection, preexisting cancer and less than 6 months of follow-up were excluded. Finally, 7248 patients (5348 and 1900 in the ETV and TDF groups, respectively) were linked to the National Cancer Registry database for the development of HCC or ICC. Propensity score matching (PSM) (2:1) analysis was used to adjust for baseline differences. The HCC incidence between two groups was not different in the entire population (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.66–1.02, p = 0.078) and in the PSM population (HR 0.83; 95% CI 0.65–1.06, p = 0.129). Among decompensated cirrhotic patients, a lower risk of HCC was observed in TDF group than in ETV group (HR 0.54; 95% CI 0.30–0.98, p = 0.043, PSM model). There were no differences between ETV and TDF groups in the ICC incidence (HR 1.84; 95% CI 0.54–6.29, p = 0.330 in the entire population and HR 1.04; 95% CI 0.31–3.52, p = 0.954 in the PSM population, respectively). In conclusion, treatment with ETV and TDF showed a comparable long-term risk of HCC and ICC in CHB patients.

Expression of Biomarkers Estrogen Receptor, Progesterone Receptor, HER2 in Primary Breast Tumour and Synchronous Metastatic Axillary Lymph Node

Introduction: Estrogen Receptor (ER), Progesterone Receptor (PR), Human Epidermal growth factor Receptor 2 (HER2) status are routinely used to guide treatment decision for breast cancer. Treatment protocol in breast cancer is currently based on biomarker characteristic of primary tumour. But this biomarker status may change as the tumour progresses from primary to synchronous metastatic lymph node. Hence, it is important to know the biomarker status of these synchronous metastatic lymph nodes as it may serve as an important tool to guide management, evaluate prognosis and to anticipate the possibility of recurrent risk of primary invasive breast cancer. Aim: To study the expression of ER, PR, HER2 status in primary breast carcinoma and synchronous metastatic lymph node and to evaluate concordance and discordance between them. Materials and Methods: This study was observational, retrospective and prospective study conducted over a period of one and half years from February 2015 to October 2016 at ESI-PGIMSR, Maniktala, Kolkata, India, where 50 cases of breast carcinoma with positive axillary lymph node metastasis were studied. Haematoxylin and Eosin (H&amp;E) sections were reviewed and representative paraffin blocks were selected. Immunostains were performed and scoring was done following standard protocols. Standard statistical methods were applied for analysis of data using chi-square test and kappa statistics and data was analysed using Statistical Package for the Social Sciences (SPSS) version 6.1.3 software. Results: Out of 50 cases the mean age of the patients was 50.56±10.5 years. Amongst ER and PR status, 24 out of 50 (48%) and 18 out of 50 (36%) were ER and PR positive respectively. HER2 positive cases were 48% i.e., 24 out of 50 cases. The overall discordance rates of ER, PR and HER2 was found to be 10%, 8%, 18%, respectively. The discordance rates of ER positive and ER negative cases were 4.2% and 15.4%, respectively. The discordance rates of PR positive and PR negative cases were 5.6% and 9.4% respectively, whereas 29.2% of HER2 positive cases were discordant in lymph node metastases. Conclusion: There was discordance between ER, PR, HER2 status of primary tumour and metastatic lymph node. Hence, assessment of these biomarker status in axillary lymph node metastases may be considered along with primary tumour in breast carcinoma work-up.