Comparison of advanced irradiation techniques with photons for benign intracranial tumours.

BACKGROUND AND PURPOSE: The potential benefits and limitations of different radiation techniques (stereotactic arc therapy (SRS/T), intensity modulated radiotherapy (IMRT), helical tomotherapy (HT), Cyberknife and intensity-modulated multiple arc therapy (AMOA)) have been assessed using comparative treatment planning methods on twelve patients presenting with 'benign' brain tumours. MATERIALS AND METHODS: Plans for five acoustic neurinomas, five meningiomas and two pituitary adenomas were computed to generate dose distributions for all modalities using a common CT dataset to delineate planning target volume and organs at risk. RESULTS: HT, AMOA and IMRT resulted superior to SRS/T and Cyberknife for target coverage. For the first group V(95%) ranged from 98% to 100%, minimum dose ranged from 91% to 96% and standard deviation from 0.84% to 1.67%. For organs at risk all techniques respected planning objectives with a tendency of Cyberknife and SRS/T to better spare the brain stem and the healthy brain tissue (e.g., V(20Gy) of 2.0% and 2.3%, respectively, compared to 3.1-5.0% for the other techniques). AMOA is in general preferable to IMRT for all OARs. Conformity index (CI(95)) was better for HT and Cyberknife (both 1.8) and less for AMOA and IMRT (3.9 and 3.0, respectively). CONCLUSION: All techniques provided good OAR sparing and primarily differed in target coverage indices. For the class of tumours investigated in this report, HT, AMOA and IMRT had better target coverage with HT providing the best combination of indeces. Between AMOA and IMRT, target coverage was comparable and, considering organs at risk, AMOA was slightly preferable.     

Acute vascular rejection is associated with systemic complement activation in a pig-to-primate kidney xenograft model

The introduction of h-DAF transgenic porcine organs into pre-clinical pig-to-primate discordant xenotransplantation has led to complete and reliable abrogation of hyperacute xenograft rejection (HAR). Despite additional heavy immunosuppression however, most xenografts are still lost due to acute vascular rejection (AVR), with current treatment protocols being of only limited value. In a life-supporting model of pig-to-primate kidney transplantation, unmodified (n=8) or h-DAF-transgenic (n=9) porcine kidneys were transplanted into cynomolgus monkeys under cyclophosphamide (CyP), cyclosporine and low-dose steroid immunosuppression. Longest recipient survival was 11 days in the control group and 68 days in the h-DAF transgenic group. Stable initial graft function with recipient survival >4 days was generated in eight animals (two controls and six transgenics). In these animals, plasma complement levels were analyzed during ongoing AVR. Compared with baseline levels, a two-fold increase in C3a levels and a four-fold increase in sC5b-9 levels were measured. In parallel to systemic complement activation, increased deposition of C3 and C5b-9 along with massive staining for recipient IgM immunoglobulins was detected in the xenografts on immunohistochemistry. We conclude that acute vascular xenograft rejection of porcine kidneys in cynomolgus monkeys is associated with classical pathway complement activation following binding of induced recipient anti-porcine antibodies. This complement activation can be observed despite membrane bound expression of human complement regulators in the porcine xenografts. Therefore, additional short-term fluid phase complement inhibition seems necessary for the future development of protocols designed for treatment of AVR in the pig-to-primate combination.     

Nephron-sparing surgery for unilateral primary renal tumor in children

PURPOSE: Definition of the role of nephron-sparing surgery (NSS) in the treatment of children with primary unilateral renal tumor (URT). METHODS: Between January 1992 and June 2000, 28 children with URT were admitted to our surgical unit. Criteria for selection of patients eligible for NSS were at least 50% of affected kidney preservable and stage I at surgery (frozen section biopsies from regional lymph nodes, perirenal fat, and surrounding renal parenchyma). Preoperative 2-drug chemotherapy was given to all patients more than 6 months of age. Between 1992 and 1995, 3-drug chemotherapy was used after NSS. Thereafter, following NSS, 2-drug chemotherapy was given if no microscopic residual disease was found on final histologic examination. RESULTS: NSS was feasible in 10 of 28 children (35%). Enucleation of 6 tumors (1 metachronous) was performed in 5 patients. NSS was elective in 5 patients, mandatory in 3 patients (1 with aniridia and genitourinary anomalies, 1 with chronic glomerulonephritis, 1 with bilateral hyperplastic nephroblastomatosis), and advisable in 2 patients (1 with familial vesicoureteric reflux and 1 with cystic nephroma). Seven children had standard histology nephroblastoma, 1 highly differentiated epithelial type nephroblastoma, 1 oncocytoma, and 1 cystic nephroma. The only post-NSS complication was macroscopic hematuria in 1 patient. None of the patients had a relapse. All children are alive and disease free with good functioning of the affected kidney after NSS, at a mean follow-up of 40.7 months (range, 2 to 100 months). CONCLUSION: NSS should be considered in selected children with URT, especially in patients with increased risk for metachronous tumor or renal disease, and in patients with benign or low-grade malignant URT.     

Chemoprevention of spontaneous tumorigenesis in nullizygous p53- deficient mice by dehydroepiandrosterone and its analog 16alpha-fluoro- 5-androsten-17-one

Transgenic mice with both alleles of the p53 tumor suppressor gene product 'knocked out' by gene targeting are susceptible to early development of tumors, chiefly lymphomas and sarcomas. Compared with the control group, administration of dehydroepiandrosterone (DHEA) at 0.3% of the diet to male p53-deficient mice extended their lifespan by delaying death due to neoplasms (from 105 to 166 days on study, P = 0.002), primarily by suppressing lymphoblastic lymphoma (from 45 to 6% of neoplastic deaths, P = 0.010). Treatment with a synthetic DHEA analog, 16alpha-fluoro-5-androsten-17-one (compound 8354), at 0.15% of the diet also increased lifespan, to 140 days for mice that developed tumors (P = 0.037). The effects of these steroids on lifespan and tumor development did not appear to be strongly related to inhibition of food consumption and weight gain, in that a group pair-fed with control diet to the reduced food consumption of the DHEA-treated group developed and died of the same types of neoplasms at the same rate as the controls fed ad libitum. The chemopreventive effect of these steroids has been proposed to be due to suppression of DNA synthesis by inhibition of glucose 6-phosphate dehydrogenase, the rate-limiting enzyme of the pentose phosphate pathway. Although DHEA and its analog are strong non- competitive inhibitors of this enzyme in vitro, treatment with DHEA did not deplete cellular nucleotide pools in the liver, as would have been predicted. The chemopreventive effect of DHEA in this model may be due to steroid-induced thymic atrophy and suppression of T cell lymphoma, permitting these mice to survive long enough to develop tumors with longer latency.      

Prevalence and impact of chronic childhood conditions in Auckland, New Zealand

Objective : To establish the prevalence of specific chronic conditions of childhood in the Auckland area and to quantify resource use by these children.
Methodology : Estimates were made from available registry data and published data sources of the population of children with selected chronic conditions resident in the Auckland Area Health Board area. Resource use data were extracted for admissions to Auckland public hospitals and from providers of community based technology services.
Results : The largest community prevalence groups are those with asthma, intellectual handicap, congenital heart disease and epilepsy. Children aged 0-14 with chronic conditions accounted for at least 14340 hospital days stay in Auckland in 1992 at an estimated minimum cost of $7.9 million. Over 200 children are dependent on technological aids at home.
Conclusions : There are sparse data on the numbers and needs of children with chronic conditions in the population. A non-categorical approach which crosses disease entities may be the best method of meeting common needs.     

Comparative analysis of dose volume histogram reduction algorithms for normal tissue complication probability calculations

A model for estimating radiotherapy treatment outcome through the probability of damage to normal tissue and the probability of tumour control is a useful tool for treatment plan optimization, dose escalation strategies and other currently used procedures in radiation oncology. Normal tissue complication estimation (NTCP) is here analysed from the point of view of the reliability and internal consistency of the most popular model. Five different dose volume histogram (DVH) reduction algorithms, applied to the Lyman model for NTCP calculation, were analysed and compared. The study was carried out for sets of parameters corresponding to quite different expected dose-response relationships. In particular, we discussed the dependence of the models on the parameters and on the dose bin size in the DVH. The sensitivity of the different reduction schemes to dose inhomogeneities was analysed, using a set of simple DVHs representing typical situations of radiation therapy routine. Significant differences were substantiated between the various reduction methods regarding the sensitivity to the degree of irradiation homogeneity, to the model parameters and to the dose bin size. Structural aspects of the reduction formalism allowed an explanation for these differences. This work shows that DVH reduction for NTCP calculation has still to be considered as a very delicate field and used with extreme care, especially for clinical applications, at least until the actual formulations are tuned against strong clinical data.     

The exchange of radiotherapy data as part of an electronic patient-referral system

Purpose: To describe the implementation and use of an electronic patient-referral system as an aid to the efficient referral of patients to a remote and specialized treatment center.

Methods and Materials: A system for the exchange of radiotherapy data between different commercial planning systems and a specially developed planning system for proton therapy has been developed through the use of the PAPYRUS diagnostic image standard as an intermediate format. To ensure the cooperation of the different TPS manufacturers, the number of data sets defined for transfer has been restricted to the three core data sets of CT, VOIs, and three-dimensional dose distributions. As a complement to the exchange of data, network-wide application-sharing (video-conferencing) technologies have been adopted to provide methods for the interactive discussion and assessment of treatments plans with one or more partner clinics.

Results: Through the use of evaluation plans based on the exchanged data, referring clinics can accurately assess the advantages offered by proton therapy on a patient-by-patient basis, while the practicality or otherwise of the proposed treatments can simultaneously be assessed by the proton therapy center. Such a system, along with the interactive capabilities provided by video-conferencing methods, has been found to be an efficient solution to the problem of patient assessment and selection at a specialized treatment center, and is a necessary first step toward the full electronic integration of such centers with their remotely situated referral centers.