NOTE The report of the Committee without its annexes appears as Official Records of the General Assembly, Sixty-third Session, Supplement No. 46. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. The country names used in this document are, in most cases, those that were in use at the time the data were collected or the text prepared. In other cases, however, the names have been updated, where this was possible and appropriate, to reflect political changes. Scientific Annexes Annex A. Medical radiation exposures Annex B. Exposures of the public and workers from various sources of radiation INTROdUCTION 1. In the course of the research and development for and the application of atomic energy and nuclear technologies, a number of radiation accidents have occurred. Some of these accidents have resulted in significant health effects and occasionally in fatal outcomes. The application of technologies that make use of radiation is increasingly widespread around the world. Millions of people have occupations related to the use of radiation, and hundreds of millions of individuals benefit from these uses. Facilities using intense radiation sources for energy production and for purposes such as radiotherapy, sterilization of products, preservation of foodstuffs and gamma radiography require special care in the design and operation of equipment to avoid radiation injury to workers or to the public. Experience has shown that such technology is generally used safely, but on occasion controls have been circumvented and serious radiation accidents have ensued. 2. Reviews of radiation exposures from accidents have been presented in previous UNSCEAR reports. The last report containing an exclusive chapter on exposures from accidents was the UNSCEAR 1993 Report [U6]. 3. This annex is aimed at providing a sound basis for conclusions regarding the number of significant radiation accidents that have occurred, the corresponding levels of radiation exposures and numbers of deaths and injuries, and the general trends for various practices. Its conclusions are to be seen in the context of the Committee's overall evaluations of the levels and effects of exposure to ionizing radiation. 4. The Committee's evaluations of public, occupational and medical diagnostic exposures are mostly concerned with chronic exposures of …

sources and effects of ionizing radiation

We explore a class of regression and generalized regression models in which the coefficients are allowed to vary as smooth functions of other variables. General algorithms are presented for estimating the models flexibly and some examples are given. This class of models ties together generalized additive models and dynamic generalized linear models into one common framework. When applied to the proportional hazards model for survival data, this approach provides a new way of modelling departures from the proportional hazards assumption

/pdf/varying-coefficient-models-tlerawxyj2.pdf

Varying-Coefficient Models

Modelling of censored survival data is almost always done by Cox proportional-hazards regression However, use of parametric models for such data may have some advantages For example, non-proportional hazards, a potential difficulty with Cox models, may sometimes be handled in a simple way, and visualization of the hazard function is much easier Extensions of the Weibull and log-logistic models are proposed in which natural cubic splines are used to smooth the baseline log cumulative hazard and log cumulative odds of failure functions Further extensions to allow non-proportional effects of some or all of the covariates are introduced A hypothesis test of the appropriateness of the scale chosen for covariate effects (such as of treatment) is proposed The new models are applied to two data sets in cancer The results throw interesting light on the behaviour of both the hazard function and the hazard ratio over time The tools described here may be a step towards providing greater insight into the natural history of the disease and into possible underlying causes of clinical events We illustrate these aspects by using the two examples in cancer

Flexible parametric proportional-hazards and proportional-odds models for censored survival data, with application to prognostic modelling and estimation of treatment effects.

Purpose To assess the clinical significance of tumor-infiltrating FOXP3-positive regulatory T cells (TR) in breast cancer patients with long-term follow-up. Patients and Methods FOXP3-positive TR were detected by immunohistochemistry with our new, extensively characterized FOXP3 monoclonal antibody, 236A/E7. Numbers of FOXP3-positive lymphocytes in tissue microarray cores from pure ductal carcinoma in situ (DCIS; n = 62), invasive breast cancer (n = 237) or from comparable areas of normal terminal duct lobular breast tissue (n = 10) were determined. A median cutoff of ≥ 15 defined patients with high numbers of TR. Results TR numbers were significantly higher in in situ and invasive breast carcinomas than in normal breast; invasive tumors have significantly higher numbers than DCIS (P = .001). High numbers of FOXP3-positive TR identified patients with DCIS at increased risk of relapse (P = .04) and patients with invasive tumors with both shorter relapse-free (P = .004) and overall survival (P = .007). High...

Quantification of Regulatory T Cells Enables the Identification of High-Risk Breast Cancer Patients and Those at Risk of Late Relapse

PURPOSETo determine if the long-term increase of recurrence for breast cancer is stable or slowly decreasing, or if it ever reaches zero; and to determine the effect of prognostic factors on the hazard of recurrence.METHODSAll patients entered onto the seven completed and unblinded Eastern Cooperative Oncology Group (ECOG) coordinated studies of postoperative adjuvant therapy for breast cancer were analyzed in terms of annual hazard of recurrence of breast cancer.RESULTSFor the entire group, the peak hazard of recurrence occurred in the interval of 1 to 2 years. The hazard decreased consistently in the interval of 2 to 5 years. Beyond 5 years, the hazard of recurrence decreased very, very slowly through year 12. The average hazard of recurrence between years 5 and 12 for the entire population was 4.3% per year. The pattern of a peak hazard of recurrence during the first 5 years with a slowly decreasing hazard of recurrence beyond 5 years was also observed to varying degrees in most subsets. Higher risk su...

Annual hazard rates of recurrence for breast cancer after primary therapy.

Pain relief and quality of life following radiotherapy for bone metastases: a randomised trial of two fractionation schedules

A retrospective analysis was made of 3878 cases of breast carcinoma first seen in Edinburgh from 1954 to 1964. During this time there was a policy to treat breast cancer by simple mastectomy and x-ray therapy, and over 90% of cases classified as international stages I and II were so treated. The mortality in these women was compared with that in an equivalent normal population using Scottish national age-specific death rates. For every year of follow-up within 20 years of initial treatment there was an excess mortality from all causes. There was an overall excess mortality of 58% among patients with breast cancer 15-20 years after initial treatment, and 20 times more deaths occurred in this period from breast cancer than in a normal population. For patients disease-free after 15 years there was still a 28% excess mortality from all causes. Factors known to be of major prognostic significance for five-year survivorship had less influence than might have been expected when the ratio of observed to expected deaths was considered for longer periods of follow-up. The effect of clinical staging (I, II, or III), though initially marked, largely disappeared by the 10th year of follow-up, and after allowing for age there was no evidence beyond 10 years of an effect on survival of the original stage of the disease. Similarly, the effect of tumour size on survival disappeared after 10 years. Women who were premenopausal at presentation still had a significant excess of deaths in the fourth quinquennium of follow-up. In the menopausal and postmenopausal groups combined there was still a small non-significant excess of deaths from all causes after 15 years but this almost disappeared when patients who had already relapsed were excluded. In terms of overall mortality only patients who have undergone the menopause before presentation and who are disease-free 15 years after primary treatment may prove to be cured by conventional techniques such as simple mastectomy and postoperative radiotherapy.

https://www.bmj.com/content/bmj/2/6200/1247.full.pdf

Long-term survival of patients with breast cancer: a study of the curability of the disease.

Purpose: Data on patients with cancer of the larynx are analyzed using statistical models to estimate the effect of gaps in the treatment time on the local control of the tumor. Methods and Materials: Patients from four centers, Edinburgh, Glasgow, Manchester, and Toronto, with carcinoma of the larynx and treated by radiotherapy were followed up and the disease-free period recorded. In all centers the end point was control of the primary tumor after irradiation alone. The local control rates at <2 years, P c , were analyzed by log linear models, and Cox proportional hazard models were used to model the disease-free period. Results: T stage, nodal involvement, and site of the tumor were important determinants of the disease-free interval, as was the radiation schedule used. Elongation of the treatment time by 1 day, or a gap of 1 day, was associated with a decrease in P c of 0.68% per day for P c = 0.80, with a 95% confidence interval of (0.28, 1.08)%. An increase of 5 days was associated with a 3.5% reduction in P c from 0.80 to 0.77. At P c = 0.60 an increase of 5 days was associated with an 7.9% decrease in P c . The time factor in the Linear Quadratic model, γ/α, was estimated as 0.89 Gy/day, 95% confidence interval (0.35, 1.43) Gy/day. Conclusions: Any gaps (public holidays are the majority) in the treatment schedule have the same deleterious effect on the disease free period as an increase in the prescribed treatment time. For a schedule, where dose and fraction number are specified, any gap in treatment is potentially damaging.

Similar decreases in local tumor control are calculated for treatment protraction and for interruptions in the radiotherapy of carcinoma of the larynx in four centers

Gillian R. Kerr

Papers

Pain relief and quality of life following radiotherapy for bone metastases: a randomised trial of two fractionation schedules

Long-term survival of patients with breast cancer: a study of the curability of the disease.

Similar decreases in local tumor control are calculated for treatment protraction and for interruptions in the radiotherapy of carcinoma of the larynx in four centers

Regression Models and Non-Proportional Hazards in the Analysis of Breast Cancer Survival

Results of radical radiotherapy of squamous cell carcinoma of the oesophagus