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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.

Objective: In patients with head and neck carcinoma of unknown primary (HNCUP;pT0) following TORS-assisted workup, we have adopted a pharyngeal-sparing radiation therapy (PSRT) approach targeting only the at-risk neck and omitting treatment of the pharynx. We report outcomes following PSRT, and compare to institutional historical control subjects who received pharyngeal-targeted RT (PRT)., Methods: Between 2009 and 2018, 172 patients underwent TORS-assisted endoscopy as part of their workup for HNCUP. Following TORS, 54 patients had pT0 disease, of which 45 received RT. Forty-nine percent received PSRT and 51% received PRT., Results: No statistically significant differences existed between the PSRT and PRT groups with respect to overall nodal distribution, p16 positivity (55% vs. 43%, P = .12), neck dissection rates (77% vs. 65%, P = .51), and administration of chemotherapy (55% vs. 65%, P = .55). Median follow-up for PSRT and PRT groups were 24 and 28 months, respectively (P = .04). Two-year RFS was 86% and 74% for PSRT and PRT patients, respectively (log-rank P = .30). Three and six patients recurred after PSRT and PRT, respectively. Two-year OS for PSRT and PRT patients was 91% and 74%, respectively (log-rank P = .31). Compared to PRT, PSRT was associated with statistically significantly less: grade 2+ mucositis (18% vs. 91%, P < .01), new opioid requirement (27% vs. 91%, P < .01), mean weight loss during RT (6.2 lbs vs. 17.4 lbs, P < .01), feeding tube placement during RT (5% vs. 43%, P < .01), and treatment-related unplanned hospitalizations (9% vs. 39%, P = .04)., Conclusion: Following TORS-assisted management of patients with pT0 HNCUP, we observed reduced toxicity following PSRT compared to PRT without apparent compromise of disease cure., Level of Evidence: Level 3 evidence, retrospective review comparing cases and controls Laryngoscope, 130:691-697, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: For patients with head and neck squamous cell carcinoma (SCC) undergoing surgery followed by postoperative radiotherapy (PORT), time from surgery to completion of adjuvant therapy, "package time" impacts locoregional control (LRC). However, the significance of package time in HPV+ oropharyngeal SCC (OPSCC) is unknown., Methods: We examined patients undergoing TORS resection with PORT for HPV+ OPSCC from January 2010 to December 2015 with ≥18 months follow-up (n = 267). A cutoff of 15 weeks was used to delineate patients into short and long package time groups. LRC loss was defined as any recurrence after surgery., Results: Prolonged package time >15 weeks was associated with inferior LRC in this HPV+ OPSCC cohort, driven primarily by interval from surgery to PORT initiation. Multivariate analysis showed that package time and T classification are both independently associated with LRC., Conclusions: Among HPV+ OPSCC, prolongation of package time appears to compromise LRC, but not survival., (© 2019 Wiley Periodicals, Inc.)

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.

Purpose: Quality of life (QOL) for patients with oropharyngeal squamous cell cancer is negatively affected by conventional radiation (RT) owing to radiation exposure to normal tissues. Proton therapy, via pencil beam scanning (PBS), can better spare many of these tissues, and may thereby improve QOL., Patients and Methods: Patient-reported outcomes were prospectively collected from patients treated from April 2013 to April 2015. Patients were treated with PBS or intensity-modulated radiation therapy (IMRT) via volumetric arc therapy after transoral robotic surgery. Validated QOL questionnaires were collected before RT, and 3, 6, and 12 months post RT., Results: Sixty-four patients were treated with adjuvant RT after transoral robotic surgery, 33 (52%) with volumetric arc therapy, and 31 (48%) with PBS. Both groups were similar in terms of age, site, stage, and dose delivered. Patients receiving PBS had significantly less dose to many normal structures than those receiving IMRT. These dosimetric advantages with PBS were reflected in higher scores in head and neck specific, as well as general, QOL measures. Most notable was significantly less xerostomia with PBS, on multiple patient-reported outcomes at multiple timepoints (6 and 12 months)., Conclusion: Pencil beam scanning, when compared to IMRT, confers a significant dosimetric advantage to many normal organs at risk, with a corresponding benefit in multiple patient-reported QOL parameters in patients receiving adjuvant RT for oropharyngeal squamous cell cancer., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to disclose., (© Copyright 2018 International Journal of Particle Therapy.)

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.

Interleukin-18 [IL-18] gene promoter polymorphism is reported to be a genetic risk factor for several types of cancer. The aims of this investigation were to evaluate and compare the frequencies of IL-18 gene promoter polymorphisms at positions -137 [G/C] and -607 [C/A] in breast cancer patients and healthy controls as well as to study the contribution of these data with clinicopathological parameters at diagnosis. The studied populations comprised 250 cases with breast carcinoma and 206 healthy subjects. IL-18 gene promoter polymorphisms at positions -137 and -607 were amplified in patient and control groups using allele specific polymerase chain reaction [AS-PCR]. The frequencies of GG, GC and CC genotypes of -137 SNP were 141 [56.4%], 96 [38.4%] and 13 [5.2%] in patients vs. 110 [53.4%], 72 [34.9%] and 24 [11.7%] in controls, respectively. A significant decrease of the CC genotype was observed in patients [p = 0.04]. The frequency of the CC genotype at position -137 was also significantly higher in patients with metastasis than non-metastatic patients [21.4% vs. 4.3%] [p = 0.02]. There was no significant association between genotype frequencies at position -607 with breast cancer or its clinicopathological parameters at diagnosis. Moreover, allelic frequencies at these positions did not contribute to breast cancer incidence. The distribution of IL-18 gene haplotypes and genotype combinations were not significantly different between patients and normal control individuals. This is the first report investigating the contribution of IL-18 gene promoter polymorphisms to breast cancer. These results suggest contrast effects of IL-18 gene in cancer induction and progression. Key words: Breast cancer, IL-18, polymorphism.

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.

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.

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.

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.

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.

Although, the cytotoxic T lymphocyte antigen-4 gene polymorphism at position 49 of exon-1 has been strongly elucidated in different autoimmune diseases, but its role in predisposition to systemic sclerosis (SSc) is yet controversial. This study intends to analyze the genetic correlation of the ctla-4 gene locus with diffuse systemic sclerosis (dSSc), as well as to understand the influence of these genotypes in disease expression. Seventy known cases of SSc, and 151 age-matched healthy controls, were participated in this investigation. The frequencies of AA, GG and AG genotypes were found to be 26 (37.1%), 5 (7.2%) and 39 (55.7%) in patients, and 60 (39.7%), 19 (12.6%) and 72 (47.7%) in controls, respectively. As indicated, the differences in genotype and allele frequencies between patients and controls were insignificant (P>0.05). Moreover, the distribution of CTLA-4 polymorphism between patients did not differ significantly according to clinical and serologic features. In Iranian patients, susceptibility to SSc is not influenced by a bi-allelic ctla-4 gene (A49G) polymorphism.