Feasibility of Proton Beam Therapy for Infants with Brain Tumours: Experiences from the Prospective KiProReg Registry Study.

AIMS: Proton beam therapy (PBT) has increasingly been applied for the treatment of young children when radiotherapy is needed. The treatment requires intensive multimodality care and is logistically demanding. In this analysis, we evaluated our experiences in treating infants with tumours of the central nervous system with PBT. MATERIALS AND METHODS: Children younger than 2 years of age treated with PBT for central nervous system tumours enrolled in the prospective registry study KiProReg were retrospectively analysed. Information on patient characteristics, treatment, toxicities and outcome were evaluated. Adverse events were classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE V4.0) before, during and after PBT. RESULTS: Between September 2013 and June 2018, 51 infants were eligible. The median age was 19 months (range 11-23 months) at the time of PBT. Tumour entities were ependymoma (51.0%), atypical teratoid rhabdoid tumour (39.0%), high-grade glioma (6.0%), pineoblastoma (2.0%) and medulloblastoma (2.0%). The prescribed median total dose was 54.0 Gy (range 45.0-59.4 Gy). Most received local radiotherapy. In four patients, craniospinal irradiation followed by a boost to the local tumour bed was applied. The median follow-up time was 42.0 months (range 7.3-86.2 months). The estimated 3-year local control, progression-free survival and overall survival rates for all patients were 62.7, 47.1 and 76.5%, respectively. During radiotherapy, 24 events of higher-grade (CTCAE ≥ °III) toxicities were reported. Interruption of radiotherapy for more than 2 days was due to infection (n = 3) or shunt complication (n = 2). Unexpected hospitalisation during radiotherapy affected 12 patients. Late adverse events attributable to radiotherapy included endocrinopathy (CTCAE °II; 7.8%), new onset of hearing loss (CTCAE °III; 5.8%) and visual impairment (CTCAE °IV; 1.9%). Transient radiation-induced imaging changes occurred in five patients (9.8%). CONCLUSIONS: Our study indicates that PBT is feasible for very young children with central nervous system tumours, at least in the short term. However, it requires challenging interdisciplinary medical care and high logistical effort. For evaluation of late effects, longer follow-up and evaluation of neurocognitive outcome are desirable. More data have to be gathered to further define the role of radiotherapy in infants over time.

Evolving Radiotherapy Techniques in Paediatric Oncology.

AIMS: Childhood cancer is rare and survival of childhood cancer has increased up to 80% at 5 years after diagnosis. Radiotherapy is an important element of the multimodal treatment concept. However, due to growing tissue, children are particularly sensitive to radiation-related side-effects and the induction of secondary malignancies. However, radiotherapy techniques have continuously progressed. In addition, modern treatment concepts have been improved in order to minimise long-term effects. Today, radiotherapy is used for various tumour types in childhood, such as sarcomas and tumours of the central nervous system. MATERIALS AND METHODS: External beam therapy with either photons or protons and brachytherapy are predominantly used for the treatment of childhood tumours. Technical developments and features, as well as clinical outcomes, for several tumour entities are presented. RESULTS: The development of radiotherapy techniques, as well as risk-adapted therapy concepts, resulted in promising outcome regarding tumour control, survival and therapy-related side-effects. It is assumed that proton therapy will be increasingly used for treating children in the future. However, more data have to be collected through multi-institutional registries in order to strengthen the evidence. CONCLUSION: The development of radiotherapy techniques is beneficial for children in terms of reducing dose exposure. As compared with other modern and highly conformal techniques, particularly proton therapy may achieve high survival rates and tumour control rates while decreasing the risk for side-effects. However, clinical evidence for modern radiotherapy techniques is still limited today. An optimal patient triaging with the selection of the most appropriate radiation technique for each individual patient will be an important goal for the future.

Retirement and wealth.

The decision to retire is related to the decision to save and to a number of other decisions, including decisions of when to claim Social Security benefits and what share of assets to hold as pensions, Social Security, and in other forms. This article explores the relationships among these various decisions and then explains why it is important to take them into account when attempting to understand the effects of changing Social Security and related policies on retirement outcomes. To understand how Social Security benefits affect retirement behavior, and the implications of changing such features as the Social Security early retirement age, the Social Security Administration and others have begun to estimate and use single-equation models of retirement. We explain why the kind of simple model they use is likely to provide a misleading guide for policy. Even if one's primary interest is in the relationship between Social Security policy and the decision to retire, it is important to incorporate other key decisions into the analysis. These simple models relate the probability of retiring to measures of changes in the value of Social Security benefits when retirement is postponed. The basic problem is that because the omitted factors are related systematically both to retirement outcomes and to the measured reward to postponing retirement, a simple retirement equation credits the effects of the omitted factors to the included measures of changes in Social Security benefits. New policies will change the relationship between retirement and the increase in the value of Social Security benefits with postponed retirement, resulting in incorrect predictions of the effects of new policies. When we fit single-equation retirement models, we find a variety of evidence that important behaviors have been omitted. These models include variables measuring the age of the respondent. These age variables suggest there is a sharp increase in the probability of retirement at age 62. This is a sign that even though the equations include measures of the increase in the value of Social Security with delayed retirement, the cause of the increased retirement behavior at age 62 has not been included in the model. In addition, the estimated effect of a variable measuring the future value of Social Security and pensions on retirement suggests that if the Social Security early retirement age were to be abolished, more people would retire earlier rather than later--a counter-intuitive prediction. There is even more direct evidence of the need for a more comprehensive model of behavior. We show that if individuals' preferences for leisure time were unrelated to their preferences for saving, then a simple retirement equation would yield an unbiased estimate of the effects of Social Security on retirement. An implication of such a model is that those who retire earlier for particular reasons would also save more for those same reasons. But when we estimate an equation with wealth accumulated through 1992 as a dependent variable, together with the simple retirement equation, we do not observe that the factors associated with earlier retirement are also associated with higher saving. These and related findings suggest that those who wish to retire earlier also have a weaker preference for saving, a relationship that is ignored in the simple model and can only be measured in a more complex model. Still other evidence also warns of internal inconsistencies in the simple retirement equations that are being estimated. Social Security incentives are often measured by the increment in the value of benefits associated with deferred retirement, but the incremental value depends on when benefits are claimed. Our findings show that those who retire completely are claiming their benefits too early to be maximizing the expected value of the benefits. Yet the measures of Social Security benefit accrual used in these retirement models often include the increase in the value of benefits from deferred claiming in their measure of the gain to deferring retirement. On the one hand, early retirees are seen not to defer benefit acceptance despite the actuarial advantage. On the other hand, later retirees are said to defer their retirement in order to gain the advantage of deferring benefit acceptance. Our empirical analysis is based on data from the first four waves of the Health and Retirement Study (HRS), a longitudinal survey of 12,652 respondents from 7,607 households with at least one respondent who was born from 1931 to 1941. Our analysis also uses linked pension and Social Security data together with respondents' records from the HRS. We also evaluate a number of specific features of retirement models and suggest improvements. We develop a measure of the future value of pensions and Social Security--the premium value--that is not subject to a problem plaguing other measures in that it handles the accrual of benefits under defined contribution plans very well. We also introduce a new definition of retirement status that blends information on objective hours worked with subjective self-reports of retirement status. Our findings also explore the effects of Social Security incentives on partial retirement and consider the importance of incorporating partial retirement in any study of the relation of Social Security to retirement behavior.

Retirement outcomes in the Health and Retirement Study.

This article examines retirement outcomes in the first four waves of the 1992-1998 Health and Retirement Study (HRS). Measured retirement is seen to differ, sometimes substantially, with the definition of retirement used and among various groups analyzed. Moreover, those differences vary with the wave of the survey as respondents age. Retirement comprises a complex set of flows among states representing nonretirement, partial retirement, and complete retirement. Using the self-reported definition of retirement, 77 percent of transitions continue in the same or equivalent states between adjoining waves of the HRS, 17 percent involve a move from greater to lesser labor force participation, and 6 percent involve a move from lesser to greater labor force participation. Twenty-two percent of the sample report they were partially retired at some time in the first four waves, and by age 65, over a fifth of the population is partially retired. Altogether, 17 percent of the sample experienced a reversal in the course of the survey, moving from a state of less work to a state of more work. A comparison of retirement flows for men between the HRS and the 1969-1979 Retirement History Study (RHS) shows that the large spike in the population leaving nonretirement at age 65 observed in the 1969-1979 RHS has fallen from 18 to 11 percentage points in the HRS and that the share leaving nonretirement at 62 has increased from 13 to 20 percentage points over time. The results presented here should help researchers improve their understanding of the structure of the dependent variable in retirement studies. Incorrect or arbitrary measurement of the retirement variable may lead to a misunderstanding of how Social Security and related policies affect retirement outcomes. Thus, the improved understanding of retirement gained from this research will be helpful to those designing retirement policies as they attempt to understand the effects of those policies.

Histiocytic differentiation in benign and malignant bone tumors.

In this study fresh frozen tissue samples of benign osseous tumors (five non-osteogenic fibromas, one fibrous dysplasia, one chondromyxoidfibroma), tumors of uncertain biological behaviour (eight cases of histiocytosis X, two giant-cell tumors), and of malignant intraosseous tumors (two malignant fibrous histiocytomas, two malignant histiocytosis, four osteosarcomas, one chondrosarcoma and two Ewing sarcomas) were studied with a panel of monoclonal antibodies reactive with monocyte/macrophages and various types of dendritic cells. In addition, tumors were further defined with a broad spectrum of antibodies against filamentous proteins and lymphocyte differentiation antigens. The specimens were stained with a triple-layer immunoalkaline phosphatase protocol. Tumors stained with these antibodies could be roughly divided into two groups. The first group comprised tumors with one predominant cell population reactive with one particular monoclonal antibody. In this group, cases of histiocytosis X were found to be consistently labelled with CD-1 antibodies. The giant-cell tumors showed a very homogeneous staining with certain monocyte/macrophage antibodies (Ki-M8). Nevertheless, even in these tumors, heterogeneity was demonstrated by the occurrence of cells with monocytic differentiation in histiocytosis X and conversely by the occurrence of cells with differentiation antigens of the dendritic cell system in giant-cell tumors. An exception has to be made for the two cases of malignant histiocytosis examined. These tumors were selectively labelled with antibodies against monocyte/macrophages (Ki-M8, IOM-1). The second group comprised tumors showing a high degree of heterogeneity demonstrated by the varying amounts of tumor cells reacting with the applied markers of the monocyte/macrophage and dendritic cell systems. In most cases it was difficult to ascribe labelled cells to the tumor cell population as opposed to an "innocent bystander" inflammatory cell population. This distinction was especially difficult in malignant fibrous histiocytomas underlining the current concept that these tumors are of primitive mesenchymal rather than true histiocytic origin.