Germline Variants in Cancer Predisposition Genes in Pediatric Patients with Central Nervous System Tumors.

Central nervous system (CNS) tumors comprise around 20% of childhood malignancies. Germline variants in cancer predisposition genes (CPGs) are found in approximately 10% of pediatric patients with CNS tumors. This study aimed to characterize variants in CPGs in pediatric patients with CNS tumors and correlate these findings with clinically relevant data. Genomic DNA was isolated from the peripheral blood of 51 pediatric patients and further analyzed by the next-generation sequencing approach. Bioinformatic analysis was done using an "in-house" gene list panel, which included 144 genes related to pediatric brain tumors, and the gene list panel Neoplasm (HP:0002664). Our study found that 27% of pediatric patients with CNS tumors have a germline variant in some of the known CPGs, like ALK, APC, CHEK2, ELP1, MLH1, MSH2, NF1, NF2 and TP53. This study represents the first comprehensive evaluation of germline variants in pediatric patients with CNS tumors in the Western Balkans region. Our results indicate the necessity of genomic research to reveal the genetic basis of pediatric CNS tumors, as well as to define targets for the application and development of innovative therapeutics that form the basis of the upcoming era of personalized medicine.

What did COVID-19 pandemics teach us about single-fraction radiotherapy for painful bone metastases-State of the art or undertreatment?

BACKGROUND: Choosing the optimal treatment approach for patients with painful bone metastases during the COVID-19 pandemic became challenging. A simple technique, single fraction radiotherapy was recommended for these patients usually referring to bone metastases as a single entity, although it is a very heterogeneous group of patients. AIM: This study aimed to analyze the response to palliative single fraction radiotherapy in relation to age, performance status, primary tumor, histopathology, and bone localization in the group of patients with painful bone metastases. METHODS: A clinical, prospective, non-randomized study was conducted at the Institute for Oncology and Radiology of Serbia, which included 64 patients with noncomplicated, painful bone metastases who underwent palliative, pain-relieving radiation therapy with a single tumor dose of 8Gy in a single hospital visit. Response to treatment was patient reported via telephone interview using visual analog scale. The response assessment was based on the international consensus panel of radiation oncologists. RESULTS: In the entire group of patients, 83% responded to radiotherapy. No statistically significant difference was observed in response to therapy, time to reach the maximum response, degree of pain reduction, nor in response duration depending on the patient's age, performance status, the primary origin of the tumor, histopathology, or location of the metastasis (bone) that was irradiated. CONCLUSION: Regardless of clinical parameters, palliative radiotherapy with a single dose of 8Gy can be considered very effective in quick pain relief in patients with noncomplicated painful bone metastases. Single fraction radiotherapy in a single hospital visit, as well as patient-reported outcome for these patients may be considered favorable beyond Covid pandemics.

Total diagnostic interval in children with brain tumours in a middle-income country: national experience from Serbia.

PURPOSE: The aim was to evaluate the total diagnostic interval (TDI) and presenting complaints in children with brain tumours in Serbia. METHODS: This study retrospectively analysed 212 children aged 0-18 years newly diagnosed with brain tumours in two tertiary centres from mid-March 2015 to mid-March 2020 covering virtually all children with brain tumours in Serbia. TDI was calculated as the difference between the date of diagnosis and the date of symptom onset presented as a median in weeks. This variable has been evaluable for 184 patients. RESULTS: Overall TDI was 6 weeks. TDI was significantly longer in patients with low-grade tumours (11 weeks) than in patients with high-grade tumours (4 weeks). Children with the most frequent complaints (headache, nausea/vomiting and gait disturbance) were more likely to be diagnosed sooner. Patients with a single complaint had significantly longer TDI (12.5 weeks) contrasted to patients with multiple complaints (5 weeks). CONCLUSION: TDI with a median of 6 weeks is similar to other developed countries. Our study supports the view that low-grade tumours will present later than high-grade tumours. Children with the commonest complaints and children with multiple complaints were more likely to be diagnosed sooner.

Clinical Profile and Outcome of 806 Pediatric Oncology Patients Treated With Radiotherapy at the Serbian National Cancer Center.

Radiotherapy plays an important role in the multimodal treatment of childhood cancer. Our objective was to provide an analysis of pediatric oncology patients treated with radiotherapy in a national referral institution in Serbia. A retrospective chart review of children treated with radiotherapy between January 2007 and July 2018 was conducted. Of the 806 patients who were identified, 767 formed the basis of this study. CNS tumors (31.2%) were the most common tumors followed by leukemias (17.3%) and bone tumors (14.3%). The most common indication for radiotherapy was in adjuvant setting (69.1%). Anesthesia or sedation was performed on 115 patients. The 5-year and 10-year overall survival rates were 65.7% and 62.1%, respectively. A significant difference in survival in relation to tumor type was seen. The best survival rates were obtained in patients with retinoblastoma, followed by lymphomas and nephroblastoma, while patients with bone sarcomas had the worst survival. The intent of radiotherapy treatment was also a parameter associated with survival. Patients treated with palliative and definitive intent lived shorter than patients treated with prophylactic and adjuvant intent. Our study showed that good treatment outcomes can be achieved in specialized centers with an experienced team of professionals who are dedicated to pediatric oncology.

Association of polymorphisms in TGFB1, XRCC1, XRCC3 genes and CD8 T-lymphocyte apoptosis with adverse effect of radiotherapy for prostate cancer.

The genetic background of each person might affect the severity of radiotherapy (RT)-induced normal tissue toxicity. The aim of study was to evaluate the influence of TGFB1 C-509T and Leu10Pro, XRCC1 Arg280His and XRCC3 Thr241Met polymorphisms as well as the level of radiation-induced CD8 T-lymphocyte apoptosis (RILA) on adverse effects of RT for prostate cancer (PCa). The study included 88 patients with localized or locally advanced PCa who were treated with RT. The polymorphisms were determined by PCR-RFLP analysis on DNA from peripheral blood mononuclear cells. RILA values were measured by flow cytometry. We found that CT genotype of TGFB1 C-509T could be protective biomarker for acute genitourinary (GU) and gastrointestinal (GI) radiotoxicity, while Thr variant of XRCC3 Thr241Met could predict the risk for acute GU radiotoxicity. Correlation between RILA values and toxicity was not detected. Univariate logistic regression analysis showed that Gleason score and risk group were risk factors for late GU, while for late GI radiotoxicity it was diabetes mellitus type 2. However, in multivariate model those were not proven to be significant and independent risk factors. Identification of assays combination predicting individual radiosensitivity is a crucial step towards personalized RT approach.

Evaluation of In Vitro Cytotoxic Potential of Avarol towards Human Cancer Cell Lines and In Vivo Antitumor Activity in Solid Tumor Models.

The goal of this study was to determine the activity in vitro and in vivo of avarol, a sesquiterpene hydroquinone originating from the Dysidea avara sponge from the south Adriatic Sea, against different cancer cell lines and two types of mouse carcinoma. To investigate the in vitro cytotoxicity, a human cervix adenocarcinoma cell line (HeLa), human colon adenocarcinoma (LS174), human non-small-cell lung carcinoma (A549), and a normal human fetal lung fibroblast cell line (MRC-5) were used. The in vivo antitumor activity was investigated against two transplantable mouse tumors, the Ehrlich carcinoma (EC) and cervical cancer (CC-5). The effect of avarol on cancer cell survival, which was determined by the microculture tetrazolium test, confirmed a significant in vitro potency of avarol against the investigated cell lines, without selectivity towards MRC-5. The highest cytotoxicity was exhibited against HeLa cancer cells (10.22 ± 0.28 µg/mL). Moreover, potent antitumor activity against two tumor models was determined, as the intraperitoneal administration of avarol at a dose of 50 mg/kg resulted in a significant inhibition of tumor growth in mice. After three administrations of avarol, a 29% inhibition of the EC growth was achieved, while in the case of CC-5, a 36% inhibition of the tumor growth was achieved after the second administration of avarol. Therefore, the results indicate that this marine sesquiterpenoid hydroquinone could be a promising bioactive compound in the development of new anticancer medicine.

Circulating levels of IL-6 and TGF-ß1 in patients with prostate cancer undergoing radiotherapy: associations with acute radiotoxicity and fatigue symptoms.

BACKGROUND: The goal of research was to investigate the possible relations between serum concentrations of IL-6 and TGF-ß1, individual and clinical characteristics, and adverse effects of radiotherapy in patients with prostate cancer: acute and late genitourinary and gastrointestinal toxicity, and fatigue. METHODS: Thirty-nine patients with localized or locally advanced prostate cancer who were treated with radiotherapy were enrolled in this study. The acute radiotoxicity grades and fatigue levels were assessed during the radiotherapy and 1 month after the radiotherapy. Estimation of the late radiotoxicity was performed every three months in the first year, every four months in the second year, and then every six months. Serum levels of IL-6 and TGF-ß1 were determined before radiotherapy and after the 25th radiotherapy fraction by ELISA. RESULTS: The significant positive association between diabetes mellitus and changes in acute genitourinary toxicity grades during the radiotherapy was observed in prostate cancer patients. In addition, patients who were smokers had significantly higher maximum fatigue levels in comparison with patients who were non-smokers. The circulating IL-6 levels were significantly higher after the 25th radiotherapy fraction in comparison with levels determined before radiotherapy. The significant positive correlations between pretreatment TGF-ß1 levels and maximum genitourinary toxicity grades and between TGF-ß1 levels after the 25th fraction and genitourinary toxicity grades after the 25th fraction, were found. The pretreatment IL-6 concentrations and TGF-ß1 concentrations after the 25th fraction were positively correlated with maximum genitourinary toxicity grades. The IL-6 levels after the 25th fraction were positively associated with genitourinary toxicity grades after this fraction. The pretreatment IL-6 concentrations were significantly positively correlated with maximum fatigue scores. The significant positive correlation between IL-6 concentrations and fatigue scores after the 25th fraction was determined. The positive correlations between IL-6 and TGF-ß1 concentrations measured after the 25th fraction and maximum fatigue scores were observed. CONCLUSIONS: Our results suggest that serum levels of IL-6 and TGF-ß1 might influence the severity of acute genitourinary radiotoxicity and fatigue in patients with prostate cancer. Combining clinical parameters and circulating cytokine levels might be useful for the prediction of adverse reactions to radiotherapy.

The Association of Polymorphisms in Genes Encoding Antioxidant Enzymes GPX1 (rs1050450), SOD2 (rs4880) and Transcriptional Factor Nrf2 (rs6721961) with the Risk and Development of Prostate Cancer.

Background and Objectives: Mounting evidence implicates oxidative damage in prostate carcinogenesis, contributing to modifications of macromolecules that drive cellular malignant transformation. Functional single-nucleotide polymorphisms (SNPs) of enzymes involved in redox homeostasis can disrupt pro-oxidant-antioxidant balance, leading to accumulation of reactive oxygen species and oxidative damage. We investigated the potential role of genetic polymorphisms of antioxidant enzymes glutathione peroxidase 1 (GPX1 rs1050450) and superoxide dismutase 2 (SOD2 rs4880) and regulatory antioxidant protein nuclear factor erythroid 2-related factor 2 (Nrf2 rs6721961) in the susceptibility to prostate cancer development (PC) and prognosis. Materials and Methods: We conducted a case-control study consisting of 235 patients with PC and 240 controls. Gene polymorphisms were determined by quantitative polymerase chain reaction (qPCR) and polymerase chain reaction with confronting two-pair primers (PCR-CTTP) methods. Multiple risk models were composed to inspect the separate and mutual effect of multiple genes and in combination with acquired contributory factors on the risk of PC development. Results: Independently, carriers of at least one SOD2*C allele had increased risk of PC development, which was significantly further amplified in advanced statistical models. When tested in combination, individuals with both SOD2*C allele and Nrf2*C/C genotype were also at increased risk of PC development, which was augmented when combined with acquired contributory factors. During the mean 75 ± 25 months of follow-up, investigated gene polymorphisms did not affect overall survival. Conclusion: Our results suggest that these gene polymorphisms could be used as risk biomarkers of PC evolution.

Association between microRNAs 10b/21/34a and acute toxicity in glioblastoma patients treated with radiotherapy and temozolomide.

A personalized approach to chemoradiation is important in reducing its potential side effects and identifying a group of patients prone to toxicity. MicroRNAs have been shown to have a predictive potential for radiotoxicity. The goal of the study was to test if levels of miRNA in peripheral blood mononuclear cells of glioblastoma patients are associated with toxicity and to identify the peak time point for toxicity. MicroRNA-10b/21/34a levels were measured in 43 patients with and without toxicity, at baseline, at the 15th, and at the 30th fraction by Real-Time quantitative Polymerase Chain Reaction. MicroRNA-10b/21 levels increased with toxicity grade (p = 0.014; p = 0.013); miR-21/34a levels were significantly different between patients with and without toxicity at the 15th fraction (p = 0.030; p = 0.045), while miR-34a levels significantly changed during treatment (p < 0.001). All three miRNAs showed a significantly high positive correlation with one another. MiR-34a might be considered as a predictive factor for toxicity due to its changes during treatment, and differences between the groups with and without toxicity; miR-10b might be used to predict toxicity; miR-10b/21 might be used for predicting the grade of toxicity in GB patients.

MicroRNAs in Prostate Cancer Following Radiotherapy: Towards Predicting Response to Radiation Treatment.

Prostate cancer (PCa) is the second most frequently diagnosed male cancer worldwide. Early diagnosis of PCa, response to therapy, and prognosis still represent a challenge. Nearly 60% of PCa patients undergo radiation therapy (RT) which might cause side effects. Despite numerous researches in this field, predictive biomarkers for radiation toxicity are still not elucidated. MicroRNAs as posttranscriptional regulators of gene expression are shown to be changed during and after irradiation. MicroRNA level changes might be utilized to predict response to RT in the near future, which might help clinicians to make the decision on treatment regimens if needed. Individual radiation response results from the interactions among radiation treatment parameters and the biological background of each patient. In this review, we have listed and described miRNAs involved in response to RT in PCa and highlighted potential candidates for future biological tests predicting radiation response to RT, with the special focus on side effects of RT. According to described literature, we concluded that let-7, miR-21, miR-34a, miR-146a, miR-155, and members of miR-17/92 cluster might be promising candidates for biological tests predicting radiosensitivity of PCa patients undergoing radiation treatment. Predictive miRNA panels, especially for acute and late side effects of RT, can serve as a starting point for decisions for individualized RT planning. We believe that this review might be one step closer to understanding molecular mechanisms underlying individual radiation response of patients with PCa.

Clinical analysis of COVID-19 positive cancer inpatients in National Cancer Center in Serbia.

INTRODUCTION: The outbreak of COVID-19 has had an impact on global healthcare as well as on radiotherapy practice in many countries. This study aimed to identify clinical characteristics of Coronavirus Disease 2019 (COVID-19) infected cancer inpatients, as well as what impact this infection had on radiation treatment of the patients. METHODOLOGY: In this retrospective study, we included cancer inpatients with laboratory confirmed COVID-19 infection during the radiotherapy or chemoradiation in April 2020 in National Cancer Research Center in Serbia. Data were obtained from the medical records between 1 April and 1 July 2020. RESULTS: A total of 49 COVID-19 infected cancer inpatients were included. The most frequently reported cancers were head and neck cancers, in twenty-three patients (46.8%). Lymphopenia was present in 77.5% of the patients. Red blood cells, haemoglobin and platelets were significantly lower during incubation or diagnosis of COVID-19. Twenty-seven (55.1%) patients did not finish radiotherapy. The age of patients who finished radiotherapy after COVID-19 infection was significantly lower compared to the patients who did not finish radiotherapy (60.5 ± 7.8 vs. 68.6 ± 11.2; p < 0.005). CONCLUSIONS: COVID-19 infected cancer patients in radiotherapy practice show similar symptoms and demographic characteristics as the general population infected with SARS-CoV-2 virus. Patients with head and neck cancers may be susceptible to infection with COVID-19. Old age and male gender may be risk factors for discontinuation of radiotherapy in COVID-19 infected cancer patients.

Clinical profile, treatment and outcome of pediatric brain tumors in Serbia in a 10-year period: A national referral institution experience.

OBJECTIVE: This study aimed to evaluate the characteristics of children with primary brain tumors, the effectiveness of treatment modalities, and to detect factors related to the outcome. METHODS: A detailed analysis was performed on a series of 173 pediatric patients treated in a Serbian referral oncology institution between 2007 and 2016, based on their clinical, histological, treatment, and follow-up data. RESULTS: Mean survival time of all children was 94.5months. 2-, 5- and 10-year overall survival probabilities were 68.8%, 59.4%, and 52.8%, respectively. Patients with supratentorial tumors had longer survival than patients with infratentorial tumors and patients with tumors in both compartments (p = 0.011). Children with the unknown histopathology (brainstem glioma) and high-grade glioma had a shorter life than embryonal tumors, ependymoma, and low-grade glioma (p<0.001). Survival of the children who underwent gross total resection was longer than the children in whom lesser degrees of resection were achieved (p = 0.015). The extent of the disease is a very important parameter found to be associated with survival. Patients with no evidence of disease after surgery had a mean survival of 123 months, compared with 82 months in patients with local residual disease and 55 months in patients with disseminated disease (p<0.001). By the univariate analysis, factors predicting poor outcome in our series were the presentation of disease with hormonal abnormalities, tumor location, and the extent of the disease, while the factors predicting a better outcome were age at the time of diagnosis, presentation of the disease with neurological deficit, and type of resection. By the multivariate analysis, the extent of the disease remained as the only strong adverse risk factor for survival (HR 2.06; 95% CI = 1.38-3.07; p<0.001). CONCLUSIONS: With an organized and dedicated multidisciplinary team, the adequate outcomes can be achieved in a middle-income country setting. The presence of local residual disease after surgery and disseminated disease has a strong negative effect on survival.

Evaluation of Cyclin D1 expression by western blotting methods and immunohistochemistry in breast cancer patients.

PURPOSE: Considering that cyclin D1 had a prognostic and clinical value for breast cancer patients, adequate measurement of cyclin D1 is necessary. METHODS: In this investigation, we detect cyclin D1 expression in tumour and peritumoral tissue of breast cancer patients by Western blotting method and by immunohistochemistry. RESULTS: Cyclin D1 expression decreased significantly with each advanced clinical stage of disease and tumour size. Also, patients without lymph node involvement, with positive hormone receptors and Luminal A type of tumours had significantly increased the expression of cyclin D1. We show that cyclin D1 expression correlates with longer RFS in the entire group of patients, in the group of ER-positive and in the group of HER2-negative patients. Patients who were both ER and cyclin D1 positive had a better prognosis. CONCLUSION: Taken together, our results, showing correlation of cyclin D1 with clinical stage, tumour size and lymph nodes, suggest that cyclin D1 expression, detected by Western blotting, could be considered as an additional marker for the staging of breast cancer, as well as a marker for longer RFS and survival in ER-positive breast cancer patients.

Polymorphisms in Genes Encoding Glutathione Transferase Pi and Glutathione Transferase Omega Influence Prostate Cancer Risk and Prognosis.

Considering the pleiotropic roles of glutathione transferase (GST) omega class members in redox homeostasis, we hypothesized that polymorphisms in GSTO1 and GSTO2 might contribute to prostate cancer (PC) development and progression. Therefore, we performed a comprehensive analysis of GSTO1 and GSTO2 SNPs' role in susceptibility to PC, as well as whether they might serve as prognostic biomarkers independently or in conjunction with other common GST polymorphisms (GSTM1, GSTT1, and GSTP1). Genotyping was performed in 237 PC cases and 236 age-matched controls by multiplex PCR for deletion of GST polymorphisms and quantitative PCR for SNPs. The results of this study, for the first time, demonstrated that homozygous carriers of both GSTO1*A/A and GSTO2*G/G variant genotypes are at increased risk of PC. This was further confirmed by haplotype analysis, which showed that H2 comprising both GSTO1*A and GSTO2*G variant alleles represented a high-risk combination. However, the prognostic relevance of polymorphisms in GST omega genes was not found in our cohort of PC patients. Analysis of the role of other investigated GST polymorphisms (GSTM1, GSTT1, and GSTP1) in terms of PC prognosis has shown shorter survival in carriers of GSTP1*T/T (rs1138272) genotype than in those carrying at least one referent allele. In addition, the presence of GSTP1*T/T genotype independently predicted a four-fold higher risk of overall mortality among PC patients. This study demonstrated a significant prognostic role of GST polymorphism in PC.

Prevalence of burnout among healthcare professionals at the Serbian National Cancer Center.

OBJECTIVE: The aim of this study was to investigate the level of burnout and identify who is at highest risk among healthcare professionals (HCPs) working at the largest referent national institution. METHODS: A cross-sectional survey was conducted at the Institute of Oncology and Radiology of Serbia from May 2019 to July 2019, evaluating the level of burnout, depression, fatigue, socio-demographic, behavioral and professional characteristics, and quality of life among healthcare professionals. Of the 576 distributed questionnaires among physicians, nurses/technicians and healthcare coworkers, 432 participants returned their questionnaires (75%). All instruments used in our study had been validated and cross-culturally adapted to Serbian language. RESULTS: The overall prevalence of burnout was 42.4%, with the greatest proportion of burned out in emotional exhaustion domain (66.9%). The multivariable-adjusted model analysis showed that nurses/technicians had a 1.41 times greater chance of experiencing burnout, compared to physicians (OR = 1.41, 95% CI 1.16-7.10), and that with each year of work experience, the chance of burnout increased by about 2% (OR = 1.02, 95% CI 1.00-1.92). Furthermore, it was shown that, with each point in the PHQ-9 score for depression, probability of burnout increased by 14% (OR = 1.14, 95% CI 1.07-1.94). Finally, after controlling all these potential confounders, the Mental Composite Score of SF-36 score showed an independent prognostic value in exploring the burnout presence among HCPs (OR = 1.17, 95% CI 1.03-2.47). CONCLUSION: Our research showed a significant level of burnout among healthcare professionals working in oncology, especially among nurses/technicians. The development of effective interventions at both individual and organizational level toward specific risk groups is needed.

Evaluation of cytokine expression and circulating immune cell subsets as potential parameters of acute radiation toxicity in prostate cancer patients.

One of the challenges of radiation oncology in the era of personalized medicine is identification of biomarkers associated with individual radiosensitivity. The aim of research was to evaluate the possible clinical value of the associations between clinical, physical, and biological factors, and risk for development of acute radiotoxicity in patients with prostate cancer. The study involved forty four patients treated with three-dimensional conformal radiotherapy. The concentrations of IL-1ß, IL-2, IL-6, IFN-γ and TGF-ß1 were assessed before radiotherapy, after 5th, 15th and 25th radiotherapy fractions, at the end, and 1 month after the end of radiotherapy. Cytokine gene expression was determined in peripheral blood mononuclear cells. The univariate analysis of circulating cytokine levels during radiotherapy showed that increased serum concentrations of IL-6 were significantly associated with higher grade of acute genitourinary toxicity. The multivariate analysis demonstrated that increased level of IL-6 during the radiotherapy was significantly associated with higher grade of acute genitourinary toxicity across treatment. TGF-ß expression levels significantly decreased during course of radiotherapy. Research indicates that changes in circulating cytokine levels might be important parameter of radiotoxicity in patients with prostate cancer. These findings suggest that future studies based on multi-parameter examination are necessary for prediction of individual radiosensitivity.

Long-lasting Thrombocytopenia after Transient Pancytopenia Induced by Short-Term Concomitant Radiotherapy and Temozolomide.

We describe long-lasting and incompletely resolved thrombocytopenia after transient profound pancytopenia in a 62-year-old female patient with glioblastoma after short-term radiotherapy with temozolomide. Pancytopenia was present for more than 4 weeks and thrombocytopenia for more than 6 months, without platelet recovery to normal levels. LEARNING POINTS: Some patients may experience severe haematological manifestations after even short-term radiotherapy with temozolomide.In everyday practice, clinical models precisely predicting the haematological toxicity of concomitant treatment with temozolomide and radiotherapy is necessary, especially in countries where genetic tests are not available.Incomplete recovery of the cells of a particular bloodline over a long period may necessitate permanent discontinuation of chemotherapy or radiotherapy.

Post-treatment FDG PET/CT predicts progression-free survival in young patients with small round blue cell tumors: Ewing sarcoma and PNET.

PURPOSE: To determine if post-treatment F-18 FDG PET/CT results (overall positive findings, specific localizations) are independent predictors of disease progression in young patients with Ewing sarcoma and Primitive neuroectodermal tumor. METHOD: A consecutive sample of 48 patients (age 14 ±â€¯5 years, 32 male) was referred to F-18 FDG PET/CT for the suspected progression of Ewing sarcoma (39 patients) and Primitive neuroectodermal tumor (PNET) (9 patients) and followed-up clinically for 4.3 ±â€¯2.3 years after F-18 FDG PET/CT (range 1-8 years). The diagnostic value of F-18 FDG PET/CT was determined in comparison to the biopsy. Kaplan-Meier analysis was used to compare progression-free survival between the groups with positive and negative F-18 FDG PET/CT findings. Variables included in the Cox regression for predicting the progression-free survival were sex, age, F-18 FDG PET/CT findings, MDCT findings, and MR ratio. RESULTS: F-18 FDG PET/CT findings were positive in 32 (67 %) patients (sensitivity 93.7 %, specificity 87.5 %, accuracy 91.7 %) with an average SUVmax of 5.8 ±â€¯3.2 (95 % CI 4.8-7.1). The progression-free survival was significantly lower (p = 0.001) in patients with positive F-18 FDG PET/CT findings (median 28 months) and when recurrence was located in bones, soft tissues, and muscles (p = 0.02, median 21 months). The significant predictors of the disease progression were the overall positive F-18 FDG PET/CT findings (HR 8.36, p = 0.004) and, specifically, the local recurrence in the bone with infiltration of soft tissue/muscles (HR 4.08, p = 0.003). CONCLUSION: Post-treatment F-18 FDG PET/CT findings are useful for predicting the progression of Ewing sarcoma and PNET and should be included in the clinical monitoring of these patients.

GSTP1 rs1138272 Polymorphism Affects Prostate Cancer Risk.

Background and Objectives: One of the most frequent genetic alterations reported to date in prostate cancer (PC) is aberrant methylation of glutathione transferase P1 (GSTP1). Taking into consideration the involvement of oxidative stress in PC pathogenesis and recent advances in scientific understanding of the role of GSTP1*Ala114Val rs1138272 polymorphism in carcinogenesis, we hypothesized that this single-nucleotide polymorphism (SNP) influences the risk of PC independently of, or in combination with, other GST polymorphisms, including GSTP1*IIe105Val rs1695 or GSTM1 and GSTT1 deletion polymorphisms. Materials and Methods: Genotyping was performed in 237 PC cases and in 236 age-matched controls by multiplex polymerase chain reaction (PCR) for deletion of GST polymorphisms and by quantitative PCR for SNPs. Results: We found that carriers of either GSTP1*Val (rs1138272) or GSTP1*Val (rs1695) variant alleles had a PC risk compared to individuals with both referent alleles (OR = 4.93, 95%CI: 2.89-8.40, p < 0.001 and OR = 1.8, 95%CI: 1.19-2.73, p = 0.006, respectively). Additionally, in a haplotype analysis we found that individuals with GSTP1*C haplotype, represented by both variant alleles (GSTP1*Val rs1695 + GSTP1*Val rs1138272), had a 5.46 times higher risk of PC development compared to individuals with the most frequent haplotype (95%CI = 2.56-11.65, p < 0.001), suggesting a potential role of those variants in PC susceptibility. A regression analysis on the number of risk-associated alleles per individual (GSTM1*active, GSTT1*null, GSTP1*Val rs1695 and GSTP1*Val rs1138272) showed a significant increase in the risk of developing PC, from 3.65-fold in carriers of two risk alleles (95%CI = 1.55-8.61, p = 0.003) to an approximately 12-fold increase in carriers of all four risk alleles (95%CI = 3.05-44.93, p < 0.001). Conclusion: Prostate cancer may be influenced by multiple glutathione transferase (GST) polymorphic genes, especially GSTP1, highlighting the role of gene-gene interactions in human susceptibility to this cancer.

Assessment of health-related quality of life among parents of children with solid tumors in Serbia.

PURPOSE: The aim of the study was to assess health-related quality of life (HRQoL) and contributing factors among parents of children with solid tumors in Serbia. METHODS: The cross-sectional study included 51 parents of children treated for different solid tumors at the Institute of Oncology and Radiology of Serbia. Parents filled out validated Serbian version of SF-36 questionnaire. Hierarchical multiple regression analysis was conducted to identify predictors of total score of SF-36. RESULTS: Almost all parents (94.1%) were mothers and average age was 38.6 ± 6.7 years. Majority of children had brain tumors (43.1%), followed by bone tumors (37.3%). The hierarchical regression analysis showed that socio-demographic characteristics explained 26% of the variance (p > 0.05) of the total score of SF-36. Addition of quality of life of children assessed by parents in the second model caused an increase of 21% in the variance explained (p < 0.05). After adding the Beck Depression Inventory score in the third block, an additional 18% of the variance in total score was explained (p < 0.05). CONCLUSIONS: This study showed that HRQoL measured by SF-36 in parents of children with cancer is strongly influenced by depression and quality of life of children assessed by parents.