Prevalence of pathogenic germline cancer risk variants in testicular cancer patients: Identifying high risk groups

Author(s):  
Chethan Ramamurthy ◽  
Amin H. Nassar ◽  
Sarah Abou Alaiwi ◽  
Elio Adib ◽  
Elie W. Akl ◽  
...  
Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 671
Author(s):  
Margherita Rimini ◽  
Pierfrancesco Franco ◽  
Berardino De Bari ◽  
Maria Giulia Zampino ◽  
Stefano Vagge ◽  
...  

Anal squamous cell carcinoma (SCC) is a rare tumor, and bio-humoral predictors of response to chemo-radiation (CT-RT) are lacking. We developed a prognostic score system based on laboratory inflammation parameters. We investigated the correlation between baseline clinical and laboratory variables and disease-free (DFS) and overall (OS) survival in anal SCC patients treated with CT-RT in five institutions. The bio-humoral parameters of significance were included in a new scoring system, which was tested with other significant variables in a Cox’s proportional hazard model. A total of 308 patients was included. We devised a prognostic model by combining baseline hemoglobin level, SII, and eosinophil count: the Hemo-Eosinophils Inflammation (HEI) Index. We stratified patients according to the HEI index into low- and high-risk groups. Median DFS for low-risk patients was not reached, and it was found to be 79.5 months for high-risk cases (Hazard Ratio 3.22; 95% CI: 2.04–5.10; p < 0.0001). Following adjustment for clinical covariates found significant at univariate analysis, multivariate analysis confirmed the HEI index as an independent prognostic factor for DFS and OS. The HEI index was shown to be a prognostic parameter for DFS and OS in anal cancer patients treated with CT-RT. An external validation of the HEI index is mandatory for its use in clinical practice.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10541-10541
Author(s):  
Bhavika K. Patel ◽  
Kay Pepin ◽  
Kathy R Brandt ◽  
Gina L. Mazza ◽  
Barbara A. Pockaj ◽  
...  

10541 Background: Biomechanical tissue properties may vary in the breasts of patients at elevated risk for breast cancer. We aim to quantify in vivo biomechanical tissue properties in various breast densities and in both normal risk and high risk women using Magnetic Resonance Imaging (MRI)/MRE and examine the association of biomechanical properties of the breast with cancer risk. Methods: In this IRB–approved prospective single-institution study, we recruited two groups of women differing by breast cancer risk to undergo a 3.0 T dynamic contrast enhanced MRI/MRE of the breast. Low-average risk women were defined as having no personal or significant family history of breast cancer, no prior high risk breast biopsies and a negative mammography within 12 months. High-risk breast cancer patients were recruited from those patients who underwent standard of care breast MR. Within each breast density group (non-dense versus dense), two-sample t-tests were used to compare breast stiffness, elasticity, and viscosity across risk groups (low-average vs high). Results: There were 50 low-average risk and 86 high-risk patients recruited to the study. The risk groups were similar on age (mean age = 55.6 and 53.6 years), density (68% vs. 64% dense breasts) and menopausal status (66.0% vs. 69.8%). Among patients with dense breasts, mean stiffness, elasticity, and viscosity were significantly higher in high risk patients ( N = 55) compared to low-average risk patients ( N = 34; all p < 0.001). In the multivariate logistic regression model, breast stiffness remained a significant predictor of risk status (OR=4.26, 95% CI [1.96, 9.25]) even after controlling for breast density, MRI BPE, age, and menopausal status. Similar results were seen for breast elasticity (OR=4.88, 95% CI [2.08, 11.43]) and viscosity (OR=11.49, 95% CI [1.15, 114.89]). Conclusions: Structurally-based, quantitative biomarker of tissue stiffness obtained from global 3D breast MRE is associated with differences in breast cancer risk in dense breasts. As such, tissue stiffness could provide a novel prognostic marker to help identify the subset of high-risk women with dense breasts who would benefit from increased surveillance.[Table: see text]


2020 ◽  
Vol 21 (9) ◽  
pp. 82-89
Author(s):  
Emel Haciislamoglu ◽  
Gorkem Gungor ◽  
Gokhan Aydin ◽  
Emine Canyilmaz ◽  
Ozan Cem Guler ◽  
...  

2010 ◽  
Vol 17 (2) ◽  
pp. 329-334 ◽  
Author(s):  
Kari Hemminki ◽  
Seyed Mohsen Mousavi ◽  
Andreas Brandt ◽  
Jianguang Ji ◽  
Jan Sundquist

The changes of cancer incidence upon immigration have been used as an estimator of environmental influence on cancer risk. The previous immigrant studies have indicated that the origins of testicular cancer are at an early age in life, probably in the intrauterine period. We wanted to reexamine the critical periods on histology-specific testicular cancer in sons of immigrants to Sweden. We used the nationwide Swedish Family-Cancer Database to calculate standardized incidence ratios (SIRs) for testicular cancer in sons of parents immigrating to Sweden from low- and high-risk countries compared with the native Swedes. Among the large immigrant groups, the SIRs for sons of two Finnish and Asian parents were decreased if the sons were born outside Sweden. The sons of a Danish immigrant couple showed an increased risk of testicular cancer. The changes in SIR were most systematic for seminoma. The present patterns of testicular cancer risk among sons of immigrants point to the early environmental risk factors, which influence the risk probably after the intrauterine period. These factors appear to influence seminoma risk in a more enduring way than they influence non-seminoma.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 542-542
Author(s):  
Martin Filipits ◽  
Peter Christian Dubsky ◽  
Margaretha Rudas ◽  
Jan C. Brase ◽  
Ralf Kronenwett ◽  
...  

542 Background: Many ER-positive, HER2-negative breast cancer patients are treated by adjuvant chemotherapy according to current clinical guidelines. We retrospectively assessed whether the combined gene expression/ clinicopathological EndoPredict-clin (EPclin) score improved the accuracy of risk classification in addition to considering clinical guidelines. Methods: Three clinical breast cancer guidelines (National Comprehensive Cancer Center Network (NCCN), German S3 and St. Gallen 2011), and the EPclin score - assessed by quantitative RT-PCR in formalin-fixed paraffin-embedded tissue - were used to assign risk groups in 1,702 ER-positive, HER2-negative breast cancer patients from two randomized phase III trials (Austrian Breast and Colorectal Cancer Study Group 6 and 8) treated with endocrine therapy only. Results: Although all analyzed clinical guidelines identified a low-risk group with improved metastasis-free survival, the overwhelming majority of all patients (81-94%) were classified as intermediate / high risk. In contrast to that, the EPclin classified only 37% of all patients as high risk and that stratification resulted in the best separation between low and high risk groups (p < 0.001, HR = 5.11 (3.48-7.51). Consequently, the majority of all patients deemed intermediate / high risk by the clinical guidelines was re-classified as low risk by the EPclin score. Kaplan Meier analyses demonstrated that the re-classified subgroups (47 to 57% of all patients) had an excellent 10-year metastasis-free survival of 95% comparable to the clinical assigned low-risk groups although encompassing a higher proportion of the trial patients. Conclusions: The EPclin score predicted distant recurrence more accurately than all three clinical guidelines and is especially useful to reclassify patients considered as intermediate / high risk by the guidelines. The data suggests that the EPclin score provides clinically useful prognostic information beyond common clinical guidelines and can be used to accurately identify the clinically relevant group of patients who are adequately and sufficiently treated with adjuvant endocrine therapy alone.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 555-555
Author(s):  
Dennis Sgroi ◽  
Yi Zhang ◽  
Catherine A. Schnabel

555 Background: Identification of N+ breast cancer patients with a limited risk of recurrence improves selection of those for which chemotherapy and/or extended endocrine therapy (EET) may be most appropriate to reduce overtreatment. BCIN+ integrates gene expression with tumor size and grade, and is highly prognostic for overall (0-10yr) and late (5-10yr) distant recurrence (DR) in N1 patients. Clinical Treatment Score post-5-years (CTS5) is a prognostic model based on clinicopathological factors (nodes, age, tumor size and grade) and significantly prognostic for late DR. The current analysis compares BCIN+ and CTS5 for risk of late DR in N1 patients. Methods: 349 women with HR+, N1 disease and recurrence-free for ≥5 years were included. BCIN+ results were determined blinded to clinical outcome. CTS5 was calculated as previously described (Dowsett et al, JCO 2018; 36:1941). Kaplan-Meier analysis and Cox proportional hazards regression for late DR (5-15y) were evaluated. Results: 64% of patients were > 50 years old, 34% with tumors > 2cm, 79% received adjuvant chemotherapy and 64% received up to 5 years of ET. BCIN+ stratified 23% of patients as low-risk with 1.3% risk for late DR vs those classified as high-risk with 16.1% [HR 12.4 (1.7-90.4), p = 0.0014]. CTS5 classified patients into 3 risk groups: 29% of patients as low-risk (4.2% DR), 37% as intermediate-risk (10.6% DR), and 34% as high-risk (22.1% DR) [HR intermediate vs. low: 2.3 (0.7-7.0), p = 0.16; high vs. low: 5.3 (1.8-15.5), p = 0.002]. In a subset of patients who completed 5 years of ET (N = 223), BCIN+ identified 22% of patients as low-risk with a late DR rate of 2.1%, while CTS5 identified 29% and 37% of patients as low- and intermediate-risk with late DR rates of 5.2% and 10.3%, respectively. Conclusions: BCIN+ classified N1 patients into binary risk groups and identified 20% patients with limited risk of late DR ( < 2%) that may be advised to forego EET and its attendant toxicities/side effects. In comparison, CTS5 classified patients into 3 risk groups, with low- and intermediate-risk of late DR of 4-5% and 10%, wherein the risk-benefit profile for extension of endocrine therapy is less clear.


2020 ◽  
Author(s):  
Humaid Al-Shamsi ◽  
Ibrahim Abu-Gheida ◽  
Amr Hassan ◽  
Fathi Azribi ◽  
Hassan Jaafar ◽  
...  

BACKGROUND Cancer care during this pandemic is challenging given the competing risks of death from cancer versus death or serious complications from SARS- CoV-2 infection, and the likely higher lethality of COVID-19 in immunocompromised patients. Question remains on serial screening for SARS-CoV-2 in asymptomatic adult cancer patients prior to anti-cancer therapy during the COVID-19 pandemic. OBJECTIVE Formulate a consensus guideline statement to guide practicing physicians METHODS We conducted a systematic review to formulate a consensus statement to guide the practising oncologists RESULTS Most of the current guidelines recommend RT-PCR SARS-CoV-2 testing of asymptomatic patients prior to initiating and during the anti-cancer therapy despite the lack of robust evidence. We suggested the following: If screening is indicated in adult cancer patients, we recommend using RT-PCR over serum antibody or serum antigen for adult cancer patients; we also recommend assessing the risk of exposure to and infection from SARS-CoV-2 prior to each anti-cancer cycle, to consider SARS-CoV-2 in asymptomatic adult cancer patients prior to anti-cancer therapy in high risk groups : highly cytotoxic chemotherapy with potential profound neutropenia based on the physician’s risk assessment of the chemotherapy , stem cell transplantation. For asymptomatic intermediate-high risk cancer patients, we suggest performing RT-PCR 48-72 hours prior to initiating any anti-cancer therapy. For asymptomatic low-risk cancer patients, we suggest not to routinely screen prior to initiating any anti-cancer therapy (weak recommendation, low quality evidence). CONCLUSIONS SARS-CoV-2 screening might be indicated with higher certainty to certain cancer risk groups. There remains a need for prospective trials to assess this intervention, and the outcome of such intervention. Current recommendations may change based on new and emerging evidence.


Author(s):  
Dawei Zhou ◽  
Junchen Wan ◽  
Jiang Luo ◽  
Yuhao Tao

Background: Liver cancer is one of the most common diseases in the world. At present, the mechanism of autophagy genes in liver cancer is not very clear. Therefore, it is meaningful to study the role and prognostic value of autophagy genes in liver cancer. Objective: The purpose of this study is to conduct a bioinformatics analysis of autophagy genes related to primary liver cancer to establish a prognostic model of primary liver cancer based on autophagy genes. Results: Through difference analysis, 31 differential autophagy genes were screened out and then analyzed by GO and KEGG analysis. At the same time, we built a PPI network. To optimize the evaluation of the prognosis of liver cancer patients, we integrated multiple autophagy genes to establish a prognostic model. By using univariate cox regression analysis, 15 autophagy genes related to prognosis were screened out. Then we included these 15 genes into the Least Absolute Shrinkage and Selection Operator (LASSO), and performed multi-factor cox regression analysis on the 9 selected genes to construct a prognostic model. The risk score of each patient was calculated based on 4 genes(BIRC5, HSP8, SQSTM1, and TMEM74) which participated in the establishing of the model, then the patients were divided into high-risk groups and low-risk groups. In the multivariate cox regression analysis, the risk score was the independent prognostic factors (HR=1.872, 95%CI=1.544-2.196, P<0.001). Survival analysis showed that the survival time of the low-risk group was significantly longer than that of the high-risk group. Combining clinical characteristics and autophagy genes, we constructed a nomogram for predicting prognosis. The external dataset GSE14520 proved that the nomogram has a good prediction for individual patients with primary liver cancer. Conclusion: This study provided potential autophagy-related markers for liver cancer patients to predict their prognosis and revealed part of the molecular mechanism of liver cancer autophagy. At the same time, the certain gene pathways and protein pathways related to autophagy may provide some inspiration for the development of anticancer drugs.


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