Impact of Biopsy Compliance on Outcomes for Patients on Active Surveillance for Prostate Cancer.

PURPOSE: Active surveillance for prostate cancer relies on regular prostate specific antigen tests and surveillance biopsies. Compliance rates with biopsies vary but the subsequent impact on oncologic outcomes is not known. The objective of this study was to determine whether noncompliance with the confirmatory biopsy negatively impacts prostate cancer specific outcomes. MATERIALS AND METHODS: A retrospective analysis was performed on a prospective single-arm cohort of men enrolled in active surveillance for prostate cancer between 1995 and 2018 with a median followup of 9.1 years. A total of 1,275 patients were enrolled and 1,043 had a minimum of 3 years of followup and were included in the analysis. Patients were stratified by compliance with a confirmatory biopsy within 24 months of enrollment in active surveillance. The primary outcome was recurrence-free survival. Secondary outcomes included metastatic-free survival and cause specific survival. RESULTS: A total of 1,275 patients were enrolled, and 1,043 had a minimum of 3 years of followup and were included in the analysis, of whom 425 were treated for localized prostate cancer. Patients noncompliant with the confirmatory biopsy had higher rates of recurrence after treatment (19% vs 12%, HR 1.64, 95% CI 1.19-2.26, p=0.003) and metastases (7% vs 2%, HR 3.56, 95% CI 1.8-7.0, p=0.0003) even after accounting for age, prostate specific antigen and Grade Group. Cause specific survival was not significantly different between the 2 groups. The results were consistent even in the subset of patients with Grade Group 1 disease at study entry. CONCLUSIONS: Noncompliance with a confirmatory biopsy compromises the control of prostate cancer in men followed on active surveillance. Patients and physicians should be aware of the importance of adhering to protocol for men on active surveillance.

Palliative Radiotherapy: Inpatients, Outpatients, and the Changing Role of Supportive Care in Radiation Oncology.

Palliative radiotherapy is an effective treatment in alleviating many symptoms of advanced cancer. Short courses of radiotherapy provide rapid symptom relief and minimize impact on patients. Patients referred for palliative radiotherapy have many concerns beyond radiotherapy; often, these concerns are not fully addressed in traditional radiotherapy clinics. Discussions of prognosis, patient goals, and concerns are areas for improved collaboration. Innovative, dedicated palliative radiotherapy programs have developed over the past 20 years to provide holistic care to patients referred for palliative radiotherapy and have improved patient-focused outcomes. Advanced radiotherapy techniques may provide opportunities to further improve palliative radiotherapy outcomes.

Spine SBRT With Halcyon™: Plan Quality, Modulation Complexity, Delivery Accuracy, and Speed.

Purpose: Spine SBRT requires treatment plans with steep dose gradients and tight limits to the cord maximal dose. A new dual-layer staggered 1-cm MLC in Halcyon™ treatment platform has improved leakage, speed, and DLG compared to 120-Millennium (0.5-cm) and High-Definition (0.25-cm) MLCs in the TrueBeam platform. Halcyon™ 2.0 with SX2 MLC modulates fluence with the upper and lower MLCs, while in Halcyon™ 1.0 with SX1 only the lower MLC modulates the fluence and the upper MLC functions as a back-up jaw. We investigated the effects of four MLC designs on plan quality for spine SBRT treatments. Methods: 15 patients previously treated at our institution were re-planned according to the NRG-BR-002 guidelines with a prescription of 3,000 cGy in 3 fractions, 6xFFF, 800 MU/min, and 3-arc VMAT technique. Planning objectives were adjusted manually by an experienced planner to generate optimal plans and kept the same for different MLCs within the same platform. Results: All treatment plans were able to achieve adequate target coverage while meeting NRG-BR002 dosimetric constraints. Planning parameters were evaluated including: conformity index, homogeneity index, gradient measure, and global point dose maximum. Delivery accuracy, modulation complexity, and delivery time were also analyzed for all MLCs. Conclusion: The Halcyon™ dual-layer MLC can generate comparable and clinically equivalent spine SBRT plans to TrueBeam plans with less rapid dose fall-off and lower conformity. MLC width leaf can impact maximum dose to organs at risk and plan quality, but does not cause limitations in achieving acceptable plans for spine SBRT treatments.

Factors influencing serum concentration of CA125 and CA15-3 in Iranian healthy postmenopausal women.

Screening for breast and ovarian cancers are required due to the late stage at diagnosis and poor survival. Serum CA125 and CA15-3 are important cancerdetecting agents in patients with ovarian and breast cancers, respectively. Elevation of CA125 and CA15-3 level correlates with malignant and non-malignant conditions. Moreover, a series of individual characteristics affect the serum level of these markers. The objective of the present study was to evaluate CA125 and CA15-3 levels in cancer-free postmenopausal women to investigate the impacts of patient parameters on the serum level of these markers. 203 subjects were studied prospectively. Serum CA125 and CA15-3 assessment was done subsequent to the direct interview. The associations between marker levels and presenting features were examined. CA125 and CA15-3 levels were elevated in 35 (17.2%) and 12 (5.9%) of persons, respectively. A higher CA125 level was associated with advanced age (p = 0.046), while a lower level was correlated with hormone replacement therapy (HRT) and having smoking habits (p = 0.000 and p = 0.01, respectively). CA15-3 level was remarkably lower amongst oral contraceptive (OCP) users (p = 0.03). Serum marker levels were not significantly related to menarche age, age at menopause, height, weight, BMI and parity. Serum CA125 is imperative indicator for malignancies of the ovary; however, personal and medical factors influence its serum level. A fair interpretation of results must be due to an accurate attention to the individual characteristics.

Substance dependency in Iranian patients with hemophilia.

AIMS: The prevalence and predisposing factors of substance dependency in 100 Iranian hemophilic patients were investigated. MEASUREMENTS: A confidential questionnaire and DSM-IV criteria were used. Data were gathered from 100 randomly selected hemophilic patients. RESULTS: The mean age of studied patients was 23.42+/-9.67 years, ranging from 12 to 74 years. The rate of substance dependency was high in hemophilic patients (39%), particularly while comparing with normal population. Prevalence of substance dependency was significantly related to age, marital status, number of family members, and being another substance-dependent in the family. Intensity of disease and its associated physical problems were not the main factors moving the patients toward substance dependency. Release of tension and enjoyment were the leading reasons for substance dependency. The nicotine was the most prevalent form of used substance. CONCLUSIONS: The high rate of substance dependency among Iranian hemophilic patients is expected due to the characteristics of disease, loss of psychiatric supports and treatment facilities and the geographic locality of the country.

Bone mineral density in beta-thalassemia major and intermedia.

OBJECTIVE: This study was conducted to assess bone mineral density (BMD) and bone mineral content (BMC) in patients with thalassemia major and intermedia, and to correlate them with biochemical and hematological profile. DESIGN: 106 thalassemic patients (49 major and 57 intermedia) were scanned by dual energy xray absorptiometry technique for BMD and BMC at lumbar spine and femoral neck. The effects of sex, transfusion/chelation program as well as hemoglobin, calcium, phosphorus, alkaline phosphatase and serum ferritin level were also evaluated on BMD and BMC. RESULTS: Patients with thalassemia major and intermedia, younger than 20 yr, showed lower BMD and BMC in the lumbar region (p < 0.05). Both parameters correlated significantly with hemoglobin level; other biochemical and hematological parameters did not influence BMD and BMC values. CONCLUSION: Bone marrow density is a good index of bone status in patients with Thalassemia and should be done in these patients annually.

Long non-coding RNAs: new frontiers for advancing personalized cancer medicine in prostate cancer.

Long non-coding RNAs (lncRNAs) are a group of non-coding transcripts of more than 200 nucleotides that play important biological and clinical roles in prostate cancer (PCa) tumorigenesis, progression and metastasis. They have also shown potential as a biomarker in the diagnosis and prognosis of this disease. LncRNA prostate cancer associated transcript-14 (PCAT-14) was recently identified as a novel prognostic biomarker in PCa, whose low expression was associated with poor outcomes. Here, we briefly discuss future perspectives and clinical applications of lncRNAs as biomarkers and therapeutic targets for PCa.

Interleukin-18 gene promoter polymorphisms and recurrent spontaneous abortion.

BACKGROUND: IL-18 is a multifunctional cytokine capable of inducing either Th1 or Th2 polarization depending on the immunologic milieu. IL-18 is detected at the materno-fetal interface very soon in early pregnancy. Two polymorphisms in the promoter region of the IL-18 gene at positions of -607 and -137 appear to have functional impacts. OBJECTIVE: This study attempts to evaluate the frequency of these two polymorphisms in the IL-18 gene promoter in patients with recurrent spontaneous abortion (RSA) and normal pregnant women. SUBJECTS AND METHODS: One hundred and two RSA patients and 103 healthy pregnant women were enrolled in this study. Single nucleotide polymorphisms of the IL-18 gene at positions -607 (C/A) and -137 (G/C) were analyzed by the sequence-specific PCR method. RESULTS: There was no significant association between the allele, genotype, and haplotype frequencies of the two single nucleotide polymorphisms (SNPs) in the IL-18 gene promoter and RSA. CONCLUSION: The results of this study showed that IL-18 gene promoter polymorphisms at positions -607 and -137 did not confer susceptibility to RSA in southern Iranian patients.

Investigation of Helicobacter pylori infection in beta-thalassaemia major patients with recurrent abdominal pain.

BACKGROUND: Recurrent abdominal pain (RAP) affects many children, especially those affected by beta-thalassaemia major. The role of Helicobacter pylori is still unclear in children with RAP. OBJECTIVES: The aim of the present study was the comparison of beta-thalassaemia major patients and normal controls with RAP in H. pylori infection. The factors influencing H. pylori prevalence were also investigated. METHODS: A series of 50 beta-thalassaemia major cases (30 female, 20 male; aged 6-25 years) and 50 age-matched and sex-matched controls, both presenting with RAP, were recruited during a period of 18 months. The study participants were obtained through a multistage random sampling method among those that met Apley's criteria. All the patients and controls had undergone diagnostic oesophagogastroduodenoscopy with biopsy. H. pylori infection was confirmed by two histopathological examinations on an endoscopy sample and a rapid urease test. RESULTS: H. pylori infection in thalassaemic patients was more common than in controls [34/50 (68%) versus 30/50 (60%)], but this higher frequency was not statistically significant. A clear relationship was found between the prevalence of H. pylori and age, duration of transfusion/chelation programmes, pain duration and splenectomy. In contrast, H. pylori did not correlate with abdominal pain characteristics, blood group, serum ferritin level and pathology of the upper gastrointestinal tract. The most frequent endoscopy abnormality was gastritis (72%). Nausea and heartburn were the leading associated symptoms. CONCLUSION: The high prevalence of H. pylori infection suggests that H. pylori should be remembered as a probable cause of RAP in beta-thalassaemia major patients.

Current challenges and future perspectives of radiotherapy for locally advanced breast cancer.

PURPOSE OF REVIEW: To discuss current issues in the field of radiation oncology for locally advanced breast cancer (LABC). RECENT FINDINGS: Large randomized studies involving nodal irradiation have recently been completed. The incremental benefit of treating the internal mammary nodes (IMNs) remains controversial. A randomized study specifically evaluating internal mammary node radiation (IMNR) failed to demonstrate significant benefit. A high impact, population-based study detected a proportional increase in major coronary events with increasing radiation dose. Advanced treatment techniques should be employed to reduce cardiac exposure. In patients with stage IV breast cancer (BCa), there is increasing evidence to suggest that locoregional treatments may improve overall survival (OS). Radiotherapy alone, without surgery, may provide equivalent local control and OS in patients with distant metastasis. High-dose stereotactic radiation regimens can be used to treat breast tumors with good local control rates in as few as three visits.BCa biomarkers are predictive of locoregional recurrence risk and should be used to guide radiotherapy in conjunction with standard staging. Clinically validated genetic profiling can measure tumor radiosensitivity and also help to predict normal tissue toxicity. SUMMARY: We are entering an era of personalized radiotherapy for LABC. Radiation treatments must be tailored to each individual patient's risk and intrinsic tumor biology.

Lineage-specific transcription factors in multipotent hematopoietic progenitors: a little bit goes a long way.

Basal expression of lineage-specific transcription factors (TFs) in multipotent hematopoietic progenitor cells (HPCs) plays a pivotal role in normal hematopoiesis. Indeed, the interplay between lineage-specific TFs and chromatin modifying or remodeling complexes allows chromatin modifications at specific hematopoietic loci and promotes transcriptionally prone conformations. During hematopoiesis, the expression of various lineage-specific genes can be preceded by their potentiation i.e., by chromatin activation, in progenitor cells. Gene potentiation appears to counterbalance epigenetic silencing of lineage-specific genes in early progenitors, while maintaining an accessible chromatin conformation in the lineage pathway selected. Herein, we discuss the impact of lineage-specific TFs on gene potentiation and priming in normal hematopoiesis, and emphasize the complementary role of locus control region (LCR) or LCR-like structures and promoter regions in gene-specific potentiation events.