Revisiting Exclusion of Prior Cancer in Clinical Trials of Male Breast Cancer

Background: Eligibility criteria for cancer clinical trials present challenges to enrollment. Many trials exclude patients with a prior cancer. This common practice may be especially detrimental to trials of rare cancers, such as male breast cancer, that struggle to accrue adequate numbers of participants. Objectives: to estimate prevalence of prior cancer among men newly diagnosed with breast cancer and describe characteristics of men with prior cancer compared to those without. Methods: We identified men diagnosed with breast cancer between 2011-2015 using population-based data from National Cancer Institute\u27s Surveillance, Epidemiology, and End Results program of cancer registries. We used sequence number and diagnosis year to identify cancers diagnosed prior to breast cancer (inclusive of prior breast, different, and unknown types of cancer). We compared sociodemographic, tumor, and treatment characteristics of men with and without prior cancer using chi-square tests. Results: Among 2317 men, nearly one quarter (24.3%) had any prior cancer, and the majority (58.7%) of these were of a different cancer type. A higher proportion of men with a prior cancer of a different type were older, had smaller (≤ 2 cm) breast tumors, were diagnosed with stage 0-1 breast cancer, and did not receive surgery compared to men without any prior cancer; there were no statistically significant differences by race and ethnicity, county median income, hormone receptor status, or surgery type. Conclusion: Given prevalence of prior cancer in this rare and understudied population of men diagnosed with breast cancer, including men with prior cancer in clinical trials may improve accrual

Potential Impact of Revised Nci Eligibility Criteria Guidance: Prior Malignancy Exclusion in Breast Cancer Clinical Trials

BACKGROUND: Many individuals with cancer have survived a prior cancer and for this reason may have been excluded from clinical trials. Recent NCI guidance recommends including these individuals, especially when the risk of the prior malignancy interfering with either safety or efficacy endpoints is very low. Using breast cancer as an example, we determined the potential effect this policy change may have on clinical trial accrual. PATIENTS AND METHODS: We reviewed protocols of NCI-sponsored breast cancer clinical trials activated in 1991 through 2016. We quantified prevalence of prior cancer-related exclusion criteria and assessed the association with trial characteristics using Fisher\u27s exact tests. Using SEER data, we estimated the prevalence and timing of prior primary (nonbreast) cancer diagnoses among patients with breast cancer. RESULTS: Among 87 clinical trials (total target enrollment, 137,253 patients), 77% excluded individuals with prior cancer, most commonly (79%) within the preceding 5 years. Among trials with radiographic response or toxicity endpoints, 69% excluded prior cancer. In SEER data, the prevalence of a prior (nonbreast) cancer diagnosis ranged from 5.7% to 7.7%, depending on breast cancer stage, of which 39% occurred within 5 years of the incident breast cancer. For trials excluding prior cancer, the estimated proportion of patients excluded for this reason ranged from 1.3% to 5.8%, with the estimated number of excluded patients ranging from 1 to 288. CONCLUSIONS: More than three-fourths of NCI-sponsored breast cancer clinical trials exclude patients with prior cancer, including almost 70% of trials with response or toxicity endpoints. Given that \u3e5% of patients with breast cancer have a history of prior cancer, in large phase III trials this practice may exclude hundreds of patients. Following recent NCI eligibility guidance, the inclusion of patients with prior cancer on breast cancer trials may have a meaningful impact on accrual

Designing a Longitudinal Survey on the Development of Iranian Children and Adolescents

Background: Investigating the effect of environmental factors, such as parental guidance and upbringing, on the individuals’ growth during their childhood and adolescence requires a long-term longitudinal study. So that, its effect on the individual cannot be sought immediately after an educational or psychological intervention. This article describes the designed protocol for the longitudinal survey of the development of Iranian children and adolescents. Methods: After performing a comparative study and reviewing similar global experiences in designing such surveys, the Iranian longitudinal survey on the development of children and adolescents was designed for five waves with a two-year interval. The longitudinal sample at the beginning of the study comprised children aged 0 to 11 years. Several questionnaires were designed for families, parents, children, adolescents and young people, teachers, and principals of schools in which the child was studying, as well as caregivers at home and kindergarten. In this survey, a three-stage probability sampling method with stratum at the provincial and national levels with two different scenarios was proposed. Findings: A roadmap for longitudinal study on the development of Iranian children and adolescents was designed and presented. Thirteen questionnaires were prepared and also, the sampling method and the method of implementing survey in different waves was determined. Conclusion: In this survey, for the first time, Iranian longitudinal studies of children and adolescents’ development have been designed with the aim of in-depth and comprehensive study of the children and adolescents’ development process and the effect of individual, family, and educational factors on their growth and development. Keywords: Longitudinal studies; Child development; Adolescents; Sampling studies; Surveys and questionnaire

Demographic aspects of human hydatidosis in Iranian general population based on serology: A systematic review and meta-analysis

Aim: Human cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus cestodes, is a globally distributed chronic disease that is an important socioeconomic and public health problem in humans and livestock in developing countries, including Iran. The aim of this study was to determine the overall seroprevalence of hydatid infection in the general population of Iran. Materials and Methods: This systematic review began by searching electronic databases in English (PubMed, Science Direct, Scopus, and Google Scholar) and Persian (Magiran, Scientific Information Database, Iran Medex, and Iran Doc). Results: Our search resulted in a total of 40 reports published from 1995 to 2015. Of 49,460 individuals surveyed, 3090 cases of hydatidosis were reported. Community-based studies showed that the seroprevalence of CE in the Iranian general population was 6.0% (95% confidence interval: 5.0-7.0%). The age group with the highest CE seroprevalence was 20-40 years, and the lowest one was in the under 20 year's group. The seroprevalence of hydatidosis in males was significantly higher than that in females. In addition, the intended rate was significantly higher in rural regions than in urban areas. Conclusion: Management program for developing more efficient diagnostic tests should be established. Further, cost-effective preventive approaches, including relevant research, should be considered. Finally, hydatid cyst control programs that are important for interrupting the transmission of human CE should be improved

Comprehensive target geometric errors and margin assessment in stereotactic partial breast irradiation

Abstract Background Recently developed stereotactic partial breast irradiation (S-PBI) allows delivery of a high biologically potent dose to the target while sparing adjacent critical organs and normal tissue. With S-PBI tumoricidal doses, accurate and precise dose delivery is critical to achieve high treatment quality. This study is to investigate both rigid and non-rigid components of target geometric error and their corresponding margins in S-PBI and identify correlated clinical factors. Methods Forty-three early-stage breast cancer patients with implanted gold fiducial markers were enrolled in the study. Fiducial positions recorded on the orthogonal kV images on a Cyberknife system during treatment were used to estimate intra-fraction errors and composite errors (including intra-fraction errors and residual errors after patient setup). Both rigid and non-rigid components of intra-fraction and composite errors were analyzed and used to estimate rigid and non-rigid margins, respectively. Univariate and multivariate linear regressions were conducted to evaluate correlations between clinical factors and errors. Results For the study group, the intra-fraction rigid and non-rigid errors are 2.0 ± 0.6 mm and 0.3 ± 0.2 mm, respectively. The composite rigid and non-rigid errors are 2.3 ± 0.5 mm and 1.3 ± 0.8 mm, respectively. The rigid margins in the left-right, anterior-posterior, and superior-inferior directions are estimated as 2.1, 2.4, and 2.3 mm, respectively. The estimated non-rigid margin, assumed to be isotropic, is 1.7 mm. The outer breast quadrants are more susceptible to composite errors occurrence than the inner breast quadrants. The target to chest wall distance is the clinical factor correlated with target geometric errors. Conclusions This is the first comprehensive analysis of breast target geometric rigid and non-rigid errors in S-PBI. Upon the estimation, the non-rigid margin is comparable to rigid margin, and therefore should be included in planning target volume as it cannot be accounted for by the Cyberknife system. Treatment margins selection also need to consider the impact of relevant clinical factor

Additional file 1: Appendix A. of Comprehensive target geometric errors and margin assessment in stereotactic partial breast irradiation

2D fiducial coordinates to 3D fiducial position conversion. Appendix B. Margin calculations. Appendix C. Multivariate linear regression model. (DOCX 29 kb