High Dose Rate Brachytherapy as Monotherapy for Localised Prostate Cancer: Review of the Current Status.

The aim of this article is to review and present the published data on high dose rate (HDR) brachytherapy as monotherapy in the treatment of localised prostate cancer. A search and review of the literature was carried out on PubMed and MedLine using the medical subject headings 'high-dose-rate, brachytherapy, prostate cancer, monotherapy' as search terms. The search yielded more than 100 articles and abstracts published between 2000 and 2016. Only original clinical data on HDR monotherapy reporting oncological outcomes were included. When more than one series from the same institution were identified, the most recent one encompassing the largest patient number was considered for analysis. For citation crosscheck, the ISI web of science database was used employing the same search terms. Data tables were generated and summary descriptions created. The main outcome parameters used were biochemical control and toxicity scores. Fifteen articles comprising 3546 patients reported clinical outcome and toxicity, with follow-up ranging from median 1.4 to 8.0 years. A variety of dose and fractionation schedules were described, including 19.0 Gy as a single fraction to 54.0 Gy in nine fractions. Biochemical control rates ranged from 66 to 100% in low-risk, 63 to 98% in intermediate-risk and 81-93% in high-risk patients. Late grade 3 genitourinary and gastrointestinal toxicity was 0-16% and 0-2%, respectively. The reported potency preservation rates ranged from 60 to 90%. In conclusion, high biochemical control and low complication rates are reported with HDR monotherapy. It is a safe and effective local treatment modality for organ-confined prostate cancer with reproducible high-quality dosimetry.

Evaluation of time, attendance of medical staff, and resources during interstitial brachytherapy for prostate cancer : DEGRO-QUIRO trial.

INTRODUCTION: The German Society of Radiation Oncology initiated a multicenter trial to evaluate core processes and subprocesses of radiotherapy by prospective evaluation of all important procedures in the most frequent malignancies treated by radiation therapy. The aim of this analysis was to assess the required resources for interstitial high-dose-rate (HDR) and low-dose-rate (LDR) prostate brachytherapy (BRT) based on actual time measurements regarding allocation of personnel and room occupation needed for specific procedures. PATIENTS AND METHODS: Two radiotherapy centers (community hospital of Offenbach am Main and community hospital of Eschweiler) participated in this prospective study. Working time of the different occupational groups and room occupancies for the workflow of prostate BRT were recorded and methodically assessed during a 3-month period. RESULTS: For HDR and LDR BRT, a total of 560 and 92 measurements, respectively, were documented. The time needed for treatment preplanning was median 24 min for HDR (n = 112 measurements) and 6 min for LDR BRT (n = 21). Catheter implantation with intraoperative HDR real-time planning (n = 112), postimplantation HDR treatment planning (n = 112), and remotely controlled HDR afterloading irradiation (n = 112) required median 25, 39, and 50 min, respectively. For LDR real-time planning (n = 39) and LDR treatment postplanning (n = 32), the assessed median duration was 91 and 11 min, respectively. Room occupancy and overall mean medical staff times were 194 and 910 min respectively, for HDR, and 113 and 371 min, respectively, for LDR BRT. CONCLUSION: In this prospective analysis, the resource requirements for the application of HDR and LDR BRT of prostate cancer were assessed methodically and are presented for first time.

Time management in radiation oncology: evaluation of time, attendance of medical staff, and resources during radiotherapy for prostate cancer: the DEGRO-QUIRO trial.

PURPOSE: In order to evaluate resource requirements, the German Society of Radiation Oncology (DEGRO) recorded the times needed for core procedures in the radio-oncological treatment of various cancer types within the scope of its QUIRO trial. The present study investigated the personnel and infrastructural resources required in radiotherapy of prostate cancer. METHODS: The investigation was carried out in the setting of definitive radiotherapy of prostate cancer patients between July and October 2008 at two radiotherapy centers, both with well-trained staff and modern technical facilities at their disposal. Personnel attendance times and room occupancy times required for core procedures (modules) were each measured prospectively by two independently trained observers using time measurements differentiated on the basis of professional group (physician, physicist, and technician), 3D conformal (3D-cRT), and intensity-modulated radiotherapy (IMRT). RESULTS: Total time requirements of 983 min for 3D-cRT and 1485 min for step-and-shoot IMRT were measured for the technician (in terms of professional group) in all modules recorded and over the entire course of radiotherapy for prostate cancer (72-76 Gy). Times needed for the medical specialist/physician were 255 min (3D-cRT) and 271 min (IMRT), times of the physicist were 181 min (3D-cRT) and 213 min (IMRT). The difference in time was significant, although variations in time spans occurred primarily as a result of various problems during patient treatment. CONCLUSION: This investigation has permitted, for the first time, a realistic estimation of average personnel and infrastructural requirements for core procedures in quality-assured definitive radiotherapy of prostate cancer. The increased time needed for IMRT applies to the step-and-shoot procedure with verification measurements for each irradiation planning.

A gEUD-based inverse planning technique for HDR prostate brachytherapy: feasibility study.

PURPOSE: The purpose of this work was to study the feasibility of a new inverse planning technique based on the generalized equivalent uniform dose for image-guided high dose rate (HDR) prostate cancer brachytherapy in comparison to conventional dose-volume based optimization. METHODS: The quality of 12 clinical HDR brachytherapy implants for prostate utilizing HIPO (Hybrid Inverse Planning Optimization) is compared with alternative plans, which were produced through inverse planning using the generalized equivalent uniform dose (gEUD). All the common dose-volume indices for the prostate and the organs at risk were considered together with radiobiological measures. The clinical effectiveness of the different dose distributions was investigated by comparing dose volume histogram and gEUD evaluators. RESULTS: Our results demonstrate the feasibility of gEUD-based inverse planning in HDR brachytherapy implants for prostate. A statistically significant decrease in D10 or/and final gEUD values for the organs at risk (urethra, bladder, and rectum) was found while improving dose homogeneity or dose conformity of the target volume. CONCLUSIONS: Following the promising results of gEUD-based optimization in intensity modulated radiation therapy treatment optimization, as reported in the literature, the implementation of a similar model in HDR brachytherapy treatment plan optimization is suggested by this study. The potential of improved sparing of organs at risk was shown for various gEUD-based optimization parameter protocols, which indicates the ability of this method to adapt to the user's preferences.

Time management in radiation oncology: development and evaluation of a modular system based on the example of rectal cancer treatment. The DEGRO-QUIRO trial.

PURPOSE: The goal was to develop and evaluate a modular system for measurement of the work times required by the various professional groups involved in radiation oncology before, during, and after serial radiation treatment (long-term irradiation with 25-28 fractions of 1.8 Gy) based on the example of rectal cancer treatment. MATERIALS AND METHODS: A panel of experts divided the work associated with providing radiation oncology treatment into modules (from the preparation of radiotherapy, RT planning and administration to the final examination and follow-up). The time required for completion of each module was measured by independent observers at four centers (Rostock, Bamberg, Düsseldorf, and Offenbach, Germany). RESULTS: A total of 1,769 data sets were collected from 63 patients with 10-489 data sets per module. Some modules (informed consent procedure, routine treatments, CT planning) exhibited little deviation between centers, whereas others (especially medical and physical irradiation planning) exhibited a wide range of variation (e.g., 1 h 49 min to 6 h 56 min for physical irradiation planning). The mean work time per patient was 12 h 11 min for technicians, 2 h 59 min for physicists, and 7 h 6 min for physicians. CONCLUSION: The modular system of time measurement proved to be reliable and produced comparable data at the different centers. Therefore, the German Society of Radiation Oncology (DEGRO) decided that it can be extended to other types of cancer (head and neck, prostate, and breast cancer) with appropriate modifications.

On the use of HDR 60Co source with the MammoSite radiation therapy system.

This work summarizes Monte Carlo results in order to evaluate the potential of using HDR 60Co sources in accelerated partial breast irradiation (APBI) with the MammoSite applicator. Simulations have been performed using the MCNP5 Monte Carlo Code, in simple geometries comprised of two concentric spheres; the internal consisting of selected concentrations, C, of a radiographic contrast solution in water (Omnipaque 300) to simulate the MammoSite balloon and the external consisting of water to simulate surrounding tissue. The magnitude of the perturbation of delivered dose due to the radiographic contrast medium used in the MammoSite applicator is calculated. At the very close vicinity of the balloon surface, a dose build-up region is observed, which leads to a dose overestimation by the treatment planning system (TPS) which depends on Omnipaque 300 solution concentration (and is in order of 2.3%, 3.0%, and 4.5%, respectively, at 1 mm away from the balloon - water interface, for C=10%, 15%, and 20%). However, dose overestimation by the TPS is minimal for points lying at the prescription distance (d=1 cm) or beyond, for all simulated concentrations and radii of MammoSite balloon. An analytical estimation of the integral dose outside the CTV in the simple geometries simulated shows that dose to the breast for MammoSite applications is expected to be comparable using HDR 60Co and 192Ir sources, and higher than that for 169Yb. The higher enegies of 60Co sources result to approximately twice radiation protection requirements as compared to 169Ir sources. However, they allow for more accurate dosimetry calculation with currently used treatment planning algorithms for 60Co sources, compared to 169Ir.

Adjuvant cytotoxic and endocrine therapy in pre- and postmenopausal patients with breast cancer and one to nine infiltrated nodes: five-year results of the Hellenic Cooperative Oncology Group randomized HE 10/92 study.

SUMMARY: The present randomized phase III trial was designed to detect a 15% benefit in relapse-free survival (RFS) or overall survival (OS) from the incorporation of adjuvant tamoxifen to the combination of CNF [cyclophosphamide, 500 mg/m2; mitoxantrone (Novantrone), 10 mg/m2; fluorouracil, 500 mg/m2 chemotherapy and ovarian ablation in premenopausal patients with node-positive breast cancer and conversely from the incorporation of CNF chemotherapy to adjuvant tamoxifen in node-positive postmenopausal patients. From April 1992 until March 1998, 456 patients with operable breast cancer and one to nine infiltrated axillary nodes entered the study. Premenopausal patients were treated with six cycles of CNF chemotherapy followed by ovarian ablation with monthly injections of triptoreline 3.75 mg for 1 year (Group A, 84 patients) or the same treatment followed by 5 years of tamoxifen (Group B, 92 patients). Postmenopausal patients received 5 years of tamoxifen (Group C, 145 patients) or 6 cycles of CNF followed by 5 years of tamoxifen (Group D, 135 patients). Adjuvant radiation was administered to all patients with partial mastectomy. After a median follow-up period of 5 years, 125 patients (27%) relapsed and 79 (17%) died. The 5-year actuarial RFS for premenopausal patients was 65% in Group A and 68% in Group B (p = 0.86) and for postmenopausal patients 70% in Group C and 67% in Group D (p = 0.36). Also, the respective OS rates were 77% and 80% (p = 0.68) for premenopausal and 84% and 78% (p = 0.10) for postmenopausal patients. Severe toxicities were infrequently seen, with the exception of leukopenia (18%), among the 311 patients treated with CNF. In conclusion, the present study failed to demonstrate a 15% difference in RFS in favor of node-positive premenopausal patients treated with an additional 5 years of tamoxifen after CNF adjuvant chemotherapy and ovarian ablation. Similarly, six cycles of CNF preceding 5 years of tamoxifen did not translate to a 15% RFS benefit in node-positive postmenopausal patients.

In vivo thermoluminescence dosimetry dose verification of transperineal 192Ir high-dose-rate brachytherapy using CT-based planning for the treatment of prostate cancer.

PURPOSE: To evaluate the potential of in vivo thermoluminescence dosimetry to estimate the accuracy of dose delivery in conformal high-dose-rate brachytherapy of prostate cancer. METHODS AND MATERIALS: A total of 50 LiF, TLD-100 cylindrical rods were calibrated in the dose range of interest and used as a batch for all fractions. Fourteen dosimeters for every treatment fraction were loaded in a plastic 4F catheter that was fixed in either one of the 6F needles implanted for treatment purposes or in an extra needle implanted after consulting with the patient. The 6F needles were placed either close to the urethra or in the vicinity of the median posterior wall of the prostate. Initial results are presented for 18 treatment fractions in 5 patients and compared to corresponding data calculated using the commercial treatment planning system used for the planning of the treatments based on CT images acquired postimplantation. RESULTS: The maximum observed mean difference between planned and delivered dose within a single treatment fraction was 8.57% +/- 2.61% (root mean square [RMS] errors from 4.03% to 9.73%). Corresponding values obtained after averaging results over all fractions of a patient were 6.88% +/- 4.93% (RMS errors from 4.82% to 7.32%). Experimental results of each fraction corresponding to the same patient point were found to agree within experimental uncertainties. CONCLUSIONS: Experimental results indicate that the proposed method is feasible for dose verification purposes and suggest that dose delivery in transperineal high-dose-rate brachytherapy after CT-based planning can be of acceptable accuracy.

Management of locally advanced prostate cancer: a European consensus.

This report summarises the findings of a European Consensus Group review of current standards of care in locally advanced prostate cancer defined as (a) untreated cancer extending clinically beyond the prostatic capsule in patients with no evidence of lymph node invasion or distant metastases, and (b) residual disease remaining after local treatment with positive surgical margins, seminal vesicle invasion, persistent prostate-specific antigen (PSA) and/or secondary PSA relapse. There was no overall consensus as to the standard of care in clinically apparent locally advanced prostate cancer. It was agreed, however, that hormonal therapy (e.g. with a gonadotrophin releasing hormone analogue [GnRHa]) represents a valid treatment in these patients. Treatment practices and regimens vary considerably between European countries, but GnRHa is widely used, either alone or in combination with antiandrogens. Hormonal therapy alone is a valid option, though the optimal modality, timing and duration of treatment remain to be defined. Adjuvant therapy with a GnRHa has been shown to improve survival in patients undergoing external beam radiotherapy. It is a viable option after prostatectomy in patients with persistent or secondary relapsing PSA. It was determined that optimal treatment will be different according to PSA, clinical staging and Gleason score, and the treatment of locally advanced disease should be individually tailored after discussion between physician and patient. In many instances, patients prefer and expect some form of treatment in preference to watchful waiting. Treatment nomograms such as the Kattan nomograms provide precise, comprehensive and invaluable tools for everyday use and may be used to predict outcomes and guide treatment decisions.

A hybrid evolutionary algorithm for multi-objective anatomy-based dose optimization in high-dose-rate brachytherapy.

Multiple objectives must be considered in anatomy-based dose optimization for high-dose-rate brachytherapy and a large number of parameters must be optimized to satisfy often competing objectives. For objectives expressed solely in terms of dose variances, deterministic gradient-based algorithms can be applied and a weighted sum approach is able to produce a representative set of non-dominated solutions. As the number of objectives increases, or non-convex objectives are used, local minima can be present and deterministic or stochastic algorithms such as simulated annealing either cannot be used or are not efficient. In this case we employ a modified hybrid version of the multi-objective optimization algorithm NSGA-II. This, in combination with the deterministic optimization algorithm, produces a representative sample of the Pareto set. This algorithm can be used with any kind of objectives, including non-convex, and does not require artificial importance factors. A representation of the trade-off surface can be obtained with more than 1000 non-dominated solutions in 2-5 min. An analysis of the solutions provides information on the possibilities available using these objectives. Simple decision making tools allow the selection of a solution that provides a best fit for the clinical goals. We show an example with a prostate implant and compare results obtained by variance and dose-volume histogram (DVH) based objectives.

Multiobjective anatomy-based dose optimization for HDR-brachytherapy with constraint free deterministic algorithms.

In high dose rate (HDR) brachytherapy, conventional dose optimization algorithms consider multiple objectives in the form of an aggregate function that transforms the multiobjective problem into a single-objective problem. As a result, there is a loss of information on the available alternative possible solutions. This method assumes that the treatment planner exactly understands the correlation between competing objectives and knows the physical constraints. This knowledge is provided by the Pareto trade-off set obtained by single-objective optimization algorithms with a repeated optimization with different importance vectors. A mapping technique avoids non-feasible solutions with negative dwell weights and allows the use of constraint free gradient-based deterministic algorithms. We compare various such algorithms and methods which could improve their performance. This finally allows us to generate a large number of solutions in a few minutes. We use objectives expressed in terms of dose variances obtained from a few hundred sampling points in the planning target volume (PTV) and in organs at risk (OAR). We compare two- to four-dimensional Pareto fronts obtained with the deterministic algorithms and with a fast-simulated annealing algorithm. For PTV-based objectives, due to the convex objective functions, the obtained solutions are global optimal. If OARs are included, then the solutions found are also global optimal, although local minima may be present as suggested.

Tumor volumetry as predictive and prognostic factor in the management of ovarian cancer.

BACKGROUND: The usefulness of tumor volumetry in ovarian epithelial cancer has never been intensively investigated. The aim of the present study was to determine the value of quantitative analysis of tumor volume as a predictive method for response to treatment and as a prognostic method for disease outcome. MATERIALS AND METHODS: Seventy-five women with advanced ovarian cancer who presented with measurable disease on CT scan prior to chemotherapy were retrospectively studied. The patients were treated with platinum-based chemotherapy. The median follow-up was 113.36 weeks. An independent radiologist identified and delineated tumor contours in each slice of sequential CT scans before and after therapy. Volumetry was measured with a three-dimensional approach by utilizing a digitizer and a specific algorithm on a software computed program. RESULTS: Data were analyzed according to initial and to residual tumor volumes. Patients with low initial volume of <52 cm3 exhibited higher responses (p<0.01), while patients with medium (52-165 cm3) or high (>165 CM3) initial tumor volume had a shorter time to progression (p<0.01). Patients without or with low residual volume of <35 cm3 were found to have a longer time to progression (p<0.05) and longer survival (p<0.01 and p<0.05). In addition, serum CA 125 levels followed precisely tumor volumetry for both initial and residual disease. CONCLUSION: Tumor volumetry in advanced ovarian cancer was found to have predictive value for response to platinum-based chemotherapy. Initial tumor volume has prognostic significance only for the time to progression, whereas residual tumor volume has for both time to progression and survival.

Brachytherapy dose-volume histogram computations using optimized stratified sampling methods.

A stratified sampling method for the efficient repeated computation of dose-volume histograms (DVHs) in brachytherapy is presented as used for anatomy based brachytherapy optimization methods. The aim of the method is to reduce the number of sampling points required for the calculation of DVHs for the body and the PTV. From the DVHs are derived the quantities such as Conformity Index COIN and COIN integrals. This is achieved by using partial uniform distributed sampling points with a density in each region obtained from a survey of the gradients or the variance of the dose distribution in these regions. The shape of the sampling regions is adapted to the patient anatomy and the shape and size of the implant. For the application of this method a single preprocessing step is necessary which requires only a few seconds. Ten clinical implants were used to study the appropriate number of sampling points, given a required accuracy for quantities such as cumulative DVHs, COIN indices and COIN integrals. We found that DVHs of very large tissue volumes surrounding the PTV, and also COIN distributions, can be obtained using a factor of 5-10 times smaller the number of sampling points in comparison with uniform distributed points.

Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG).

BACKGROUND: Concurrent platinum etoposide chemotherapy given in combination with hyperfractionated thoracic radiation therapy (HTRT) in limited disease (LD) small cell lung cancer (SCLC) is associated with a high response rate and significant prolongation of survival. Given these results, the Hellenic Cooperative Oncology Group (HeCOG) performed a multicenter randomized phase II study in patients with LD SCLC to evaluate the timing of HTRT (early vs. late) when given concurrently with chemotherapy. PATIENTS AND METHODS: To be eligible for the study, patients were required to have histologically or cytologically proven LD SCLC, confined to one hemithorax and/or ipsilateral mediastinal or supraclavicular lymphnodes and absence of pleural effusion or controlateral supraclavicular lymphnode involvement. Moreover, patients had to have a good performance status and adequate haematological, liver and renal function. Patients with LD SCLC were randomized to receive HTRT either concurrently with the first (Group A) or with the fourth (Group B) cycle of chemotherapy. Chemotherapy consisted of carboplatin administered at an AUC of six given as an i.v. 1-hour-infusion immediately followed by etoposide at a dose of 100 mg/m2 i.v. as a two-hour infusion for three consecutive days every three weeks up to a total of six cycles. Prophylactic cranial irradiation was also given to patients achieving a complete response. RESULTS: 42 and 39 patients, were eligible for efficacy evaluation in group A and B respectively. The overall response rate was 76% in group A and 92.5% in group B (P = 0.07) with a complete response rate of 40.5% and 56.5%, respectively. After a median follow-up of 35 months, time to progression was 9.5 months in group A and 10.5 in group B (NS) while overall median survival was 17.5 and 17 months respectively (NS). The 2-year survival was 36% in group A and 29% in group B (NS) and the 3-year survival 22% and 13%, respectively (NS). The distant relapse rate was 38% in group A and 61% in group B (P = 0.046). Severe grade 3 4 anemia was recorded in 19% of group A and 12.5% of group B (NS), while severe leucopenia was recorded in 35.5% and 20.5% (P = 0.09) and neutropenic fever in 5% and 2.5% (NS), respectively. Severe thrombocytopenia did not differ significantly between the two treatment groups being 21.5% and 23%, respectively. Severe grade 2-3 esophageal toxicity was 19% in group A and 23% in group B (NS), while grade 3 lung toxicity was 5% and 7.5% (NS), respectively. No toxicity-related deaths were recorded. CONCLUSION: Concurrent administration of HTRT with carboplatin etoposide is associated with a high response and survival rate. Although a trend for higher response rate was recorded in the group of patients who received late HTRT, the overall median, 2-year and 3-year survival rates did not differ significantly between the two treatment groups. The toxicity of this promising therapeutic approach was acceptable. Comparative phase III studies with an adequate number of patients are recommended in order to answer this question.

Beta versus gamma dosimetry close to Ir-192 brachytherapy sources.

The relative importance of the dose rate component owing to the beta spectrum emitted by 192Ir brachytherapy sources at the short radial distances of interest in intravascular and endobronchial applications is investigated. Separate dosimetric calculations, using Monte Carlo simulations, were performed for the gamma and beta dose rate components of an 192Ir ideal point source as well as real 192Ir source designs used in clinical practice including wire and seed sources and both Nucletron and Varian, old and new, high dose rate (HDR) source designs. A significant dose rate enhancement due to the beta spectrum emitted by 192Ir, greater than 50% for radial distances r<2 mm, was observed for an ideal point source. For real source designs, however, the magnitude of this enhancement was found to depend strongly on the sources' geometric as well as compositional details of the active core and encapsulation. A detectable effect was found for the majority of the investigated sources at radial distances less than 1 mm, but overall findings suggest that the contribution of beta particles is not significant in 192Ir clinical intravascular applications that are currently carried out. However, since treatment of vessels with smaller diameters, in the future, may lead to the development of 192Ir sources and catheters of reduced diameters, the potential effect of the beta spectrum in terms of dose enhancement to tissues in close proximity to 192Ir sources should not be ignored.

Correcting organ motion artifacts in x-ray CT systems based on tracking of motion phase by the spatial overlap correlator. II. Experimental study.

This paper presents the experimental part of an investigation on tracking and eliminating organ motion artifacts in x-ray CT cardiac applications with emphasis on imaging coronary calcification. The system methodology consists of a software implementation of the spatial overlap correlator (SSOC) concept in x-ray CT scanners to track the net amplitude and phase of organ motion during the CT data acquisition process. A coherent sinogram synthesis (CSS) method is then used to identify the repeated phases of a periodic organ motion from the information provided by the SSOC process and hence synthesize a new sinogram with no motion effects. Since the SSOC scheme is capable of tracking cardiac motion, it identifies also the projection points associated with minimum amplitude cardiac motion effects. These points are used to identify a 180 degrees plus the fan angle sinogram for image reconstruction. This leads to a retrospective gating (RG) scheme that is based on the output of the SSOC process. Performance comparison of the proposed methodology with the retrospective ECG gating using real data sets with phantoms and human patients provides a performance assessment of the merits of the proposed methods. Real results demonstrate that the new methodology eliminates the requirement for ECG gating. Moreover, the CSS and the new RG methods do not require breath holding and they can be implemented in x-ray CT scanners to image coronary calcification and the heart's ventricles.

Long-term effects on the intelligence of children treated for acute lymphoblastic leukemia.

The purpose of this study was to investigate whether the intelligence quotient (IQ) in children treated for leukemia decreases in the years following whole brain irradiation. Twenty-seven leukemic children were assessed following a mean time lapse between radiotherapy and IQ measurement of 9 years. The IQ test used was the Hamburg Weschsler Intelligence Test for Adults. The IQ results did not differ significantly, p > 0.05, from the IQs of the general population. It was found that age and dose were not predictors of a decrease in IQ. The only predictor was time lapse between irradiation and IQ measurement, which we found to be indicative of an IQ decrease even after 9 years. Time lapse between irradiation is a useful predictor of IQ.