A step towards international prospective trials in carbon ion radiotherapy: investigation of factors influencing dose distribution in the facilities in operation based on a case of skull base chordoma.

BACKGROUND: Carbon ion radiotherapy (CIRT) has been delivered to more than 20,000 patients worldwide. International trials have been recommended in order to emphasize the actual benefits. The ULICE program (Union of Light Ion Centers in Europe) addressed the need for harmonization of CIRT practices. A comparative knowledge of the sources and magnitudes of uncertainties altering dose distribution and clinical effects during the whole CIRT procedure is required in that aim. METHODS: As part of ULICE WP2 task group, we sent a centrally reviewed questionnaire exploring candidate sources of uncertainties in dose deposition to the ten CIRT facilities in operation by February 2017. We aimed to explore native beam characterization, immobilization, anatomic data acquisition, target volumes and organs at risks delineation, treatment planning, dose delivery, quality assurance prior and during treatment. The responders had to consider the clinical case of a clival chordoma eligible for postoperative CIRT according to their clinical practice. With the results, our task group discussed ways to harmonize CIRT practices. RESULTS: We received 5 surveys from facilities that have treated 77% of the patients worldwide per November 2017. We pointed out the singularity of the facilities and beam delivery systems, a divergent definition of target volumes, the multiplicity of TPS and equieffective dose calculation approximations. CONCLUSION: Multiple uncertainties affect equieffective dose definition, deposition and calculation in CIRT. Although it is not possible to harmonize all the steps of the CIRT planning between the centers, our working group proposed counter-measures addressing the improvable limitations.

Concepts and terms for dose/volume parameters in carbon-ion radiotherapy: Conclusions of the ULICE taskforce.

PURPOSE: The Union of Light Ion Centers in Europe (ULICE) program addressed the need for uniting scientific results for carbon-ion radiation therapy obtained by several institutions worldwide in different fields of excellence, and translating them into a real benefit to the community. Particularly, the concepts for dose/volume parameters developed in photon radiotherapy cannot be extrapolated to high linear energy transfer particles. METHODS AND MATERIALS: The ULICE-WP2 taskforce included radiation oncologists involved in carbon-ion radiation therapy and International Commission on Radiation Units and Measurements, radiation biologists, expert physicists in the fields of carbon-ion radiation therapy, microdosimetry, biological modeling and image-guided radiotherapy. Consensual reports emerged from multiple discussions within both the restricted group and the wider ULICE community. Public deliverables were produced and disseminated to the European Commission. RESULTS: Here we highlight the disparity in practices between treating centers, then address the main topics to finally elaborate specific recommendations. Although it appears relatively simple to add geometrical margins around the clinical target volume to obtain the planning target volume as performed in photon radiotherapy, this procedure is not appropriate for carbon-ion radiation therapy. Due to the variation of the radiation quality in depth, there is no generic relative biological effectiveness value for carbon-ions outside of an isolated point, for a given fractionation and specific experimental conditions. Absorbed dose and "equieffective dose" for specified conditions must always be reported. CONCLUSIONS: This work contributed to the development of standard operating procedures for carbon-ion radiation therapy clinical trials. These procedures are now being applied, particularly in the first phase III international, multicenter trial (PHRC Étoile).

Fifteen symposia on microdosimetry: implications for modern particle-beam cancer radiotherapy.

The objective of microdosimetry was, and still is, to identify physical descriptions of the initial physical processes of ionising radiation interacting with biological matter which correlate with observed radiobiological effects with a view to improve the understanding of radiobiological mechanisms and effects. The introduction of therapy with particles starting with fast neutrons followed by negative pions, protons and light ions necessitated the application of biological weighting factors for absorbed dose in order to account for differences of the relative biological effectiveness (RBE). Dedicated radiobiological experiments in therapy beams with mammalian cells and with laboratory animals provided sets of RBE values which are used to evaluate empirical 'clinical RBE values'. The combination of such experiments with microdosimetric measurements in identical conditions offered the possibility to establish semi-empirical relationships between microdosimetric parameters and results of RBE studies.

Isoeffective dose: a concept for biological weighting of absorbed dose in proton and heavier-ion therapies.

When reporting radiation therapy procedures, International Commission on Radiation Units and Measurements (ICRU) recommends specifying absorbed dose at/in all clinically relevant points and/or volumes. In addition, treatment conditions should be reported as completely as possible in order to allow full understanding and interpretation of the treatment prescription. However, the clinical outcome does not only depend on absorbed dose but also on a number of other factors such as dose per fraction, overall treatment time and radiation quality radiation biology effectiveness (RBE). Therefore, weighting factors have to be applied when different types of treatments are to be compared or to be combined. This had led to the concept of 'isoeffective absorbed dose', introduced by ICRU and International Atomic Energy Agency (IAEA). The isoeffective dose D(IsoE) is the dose of a treatment carried out under reference conditions producing the same clinical effects on the target volume as those of the actual treatment. It is the product of the total absorbed dose (in gray) used and a weighting factor W(IsoE) (dimensionless): D(IsoE)=D×W(IsoE). In fractionated photon-beam therapy, the dose per fraction and the overall treatment time (in days) are the two main parameters that the radiation oncologist has the freedom to adjust. The weighting factor for an alteration of the dose per fraction is commonly evaluated using the linear-quadratic (α/ß) model. For therapy with protons and heavier ions, radiation quality has to be taken into account. A 'generic proton RBE' of 1.1 for clinical applications is recommended in a joint ICRU-IAEA Report [ICRU (International Commission on Radiation Units and Measurements) and IAEA (International Atomic Energy Agency). Prescribing, recording and reporting proton-beam therapy. ICRU Report 78, jointly with the IAEA, JICRU, 7(2) Oxford University Press (2007)]. For heavier ions (e.g. carbon ions), the situation is more complex as the RBE values vary markedly with particle type, energy and depth in tissue.

Response to 'Patient dose measurements in radiological practices'.

A lack of suitable dosimetric quantities for application in diagnostic radiology is noted by Dr Moores. It is concluded by Dr Moores that it is not possible to adhere to the basic principles of the International Commission on Radiation Units and Measurements (ICRU) regarding patient dosimetry in diagnostic radiology due to the extremely wide variety of quantities and units employed. The conclusion of the ICRU on similar observations, however, was that there is a need for harmonization of quantities and terminology for dosimetry in diagnostic and interventional radiology and they established a Report Committee with the aim of formulating an ICRU report on 'dosimetric procedures in diagnostic radiology'. The report produced by this committee entitled 'Patient dosimetry for x rays used in medical imaging' was accepted for publication in December 2005 and is currently at press, and may serve to improve the current situation with regard to patient dose measurement in diagnostic and interventional radiology.

The RBE issues in ion-beam therapy: conclusions of a joint IAEA/ICRU working group regarding quantities and units.

This paper summarises the conclusions of a working group established jointly by the International Atomic Energy Agency (IAEA) and the International Commission on Radiation Units and Measurements (ICRU) to address some of the relative biological effectiveness (RBE) issues encountered in ion-beam therapy. Special emphasis is put on the selection and definition of the involved quantities and units. The isoeffective dose, as introduced here for radiation therapy applications, is the dose that delivered under reference conditions would produce the same clinical effects as the actual treatment in a given system, all other conditions being identical. It is expressed in Gy. The reference treatment conditions are: photon irradiation, 2 Gy per fraction, 5 daily fractions a week. The isoeffective dose D(IsoE) is the product of the physical quantity absorbed dose D and a weighting factor W(IsoE). W(IsoE) is an inclusive weighting factor that takes into account all factors that could influence the clinical effects like dose per fraction, overall time, radiation quality (RQ), biological system and effects. The numerical value of W(IsoE) is selected by the radiation-oncology team for a given patient (or treatment protocol). It is part of the treatment prescription. Evaluation of the influence of RQ on W(IsoE) raises complex problems because of the clinically significant RBE variations with biological effect (late vs. early) and position in depth in the tissues which is a problem specific to ion-beam therapy. Comparison of the isoeffective dose with the equivalent dose frequently used in proton- and ion-beam therapy is discussed.

Radiation exposure and cause specific mortality among nuclear workers in Belgium (1969-1994).

Cause specific mortality was studied in nuclear workers from five nuclear facilities in Belgium and compared to the general population. For the 1969-1994 period, mortality in male nuclear workers is significantly lower for all causes of death and for all cancer deaths. The same conclusions are reached if one assumes a latency period of 20 y between the first irradiation and cancer induction. In female workers, mortality due to all causes and all cancer deaths is not different from that of the general population. Analysis of cause specific mortality was performed for male and female workers for three endpoints: specific cancer sites, cardiovascular and respiratory diseases. No significant increase in mortality was observed. In male workers, the influence of cumulative dose was also investigated using four dose levels: no significant correlation was found. Smoking habits may be a confounding factor in smoking related health conditions.

Characteristics of dosemeter types for skin dose measurements in practice.

A growing number of papers report deterministic effects in the skin of patients who have undergone interventional radiological procedures. Dose measurements, and especially skin dose measurements, are therefore increasingly important. Methods and acceptable dosemeters are, however, not clearly defined. This paper is the result of a literature overview with regard to assessing the entrance skin dose during radiological examinations by putting a dosemeter on the patient's skin. The relevant intrinsic characteristics, as well as some examples of clinical use of the different detector types, are presented. In this respect, thermoluminescence, scintillation, semiconductor and film dosemeters are discussed and compared with respect to their practical use.

The ICRU (International Commission on Radiation Units and Measurements): its contribution to dosimetry in diagnostic and interventional radiology.

The ICRU (International Commission on Radiation Units and Measurements was created to develop a coherent system of quantities and units, universally accepted in all fields where ionizing radiation is used. Although the accuracy of dose or kerma may be low for most radiological applications, the quantity which is measured must be clearly specified. Radiological dosimetry instruments are generally calibrated free-in-air in terms of air kerma. However, to estimate the probability of harm at low dose, the mean absorbed dose for organs is used. In contrast, at high doses, the likelihood of harm is related to the absorbed dose at the site receiving the highest dose. Therefore, to assess the risk of deterministic and stochastic effects, a detailed knowledge of absorbed dose distribution, organ doses, patient age and gender is required. For interventional radiology, where the avoidance of deterministic effects becomes important, dose conversion coefficients are generally not yet developed.

Biological weighting of absorbed dose in radiation therapy.

Absorbed dose is a quantity which is scientifically rigorously defined and used to quantify the exposure of biological objects, including humans, to ionising radiation. There is, however, no unique relationship between absorbed dose and induced biological effects. The effects induced by a given absorbed dose to a given biological object depend also on radiation quality and temporal distribution of the irradiation. In radiation therapy, empirical approaches are still used today to account for these dependencies in practice. In hadron therapy (neutrons, protons, ions), radiation quality is accounted for with a diversity of (almost hospital specific) methods. The necessity to account for temporal aspects is well known in external beam therapy and in high dose rate brachytherapy. The paper reviews the approaches for weighting the absorbed dose in radiation therapy, and focusses on the clinical aspects of these approaches, in particular the accuracy requirements.

Proton RBE for early intestinal tolerance in mice after fractionated irradiation.

BACKGROUND AND PURPOSE: To determine the influence of the number of fractions (or the dose per fraction) on the proton relative biological effectiveness (RBE). MATERIALS AND METHODS: Intestinal crypt regeneration in mice was used as the biological endpoint. RBE was determined relative to cobalt-60 gamma rays for irradiations in one, three and ten fractions separated by a time interval of 3.5h. Proton irradiations were performed at the middle of a 7-cm Spread Out Bragg Peak (SOBP). RESULTS: Proton RBEs (and corresponding gamma dose per fraction) at the level of 20 regenerated crypts per circumference were found equal to 1.15+/-0.04 (10.0 Gy), 1.15+/-0.05 (4.8 Gy) and 1.14+/-0.07 (1.7 Gy) for irradiations in one, three and ten fractions, respectively. Alpha/beta ratios as derived from direct analysis of the 'quantal radiation response data' were found to be 7.6 Gy for gamma rays and 8.2 Gy for protons. Additional proton irradiations in ten fractions at the end of the SOBP were found to be more effective than at the middle of the SOBP by a factor of 1.14 (1.05-1.23). CONCLUSION: Proton RBE for crypt regeneration was found to be independent of fractionation up to ten fractions. One can expect that it remains unchanged for higher number of fractions as the lethalities for doses smaller than 3 Gy are exclusively due to direct lethal events. As a tendency for increased effectiveness at the end of the SOBP is reported in the majority of the studies, for clinical applications it would be advisable to allow for by arranging a sloping depth dose curve in the deeper part of the target volume. Finally, it must be noticed that most of in vitro and in vivo RBE values for protons are larger than the current clinical RBE (RBE=1.10).

A retrospective analysis of the results of p(65) + Be neutrontherapy for the treatment of prostate adenocarcinoma at the cyclotron of Louvain-la-Neuve. Part I: Survival and progression-free survival.

PURPOSE: To retrospectively evaluate survival, progression-free survival (PFS) and biological response in a series of patients irradiated with mixed neutron/photon beams for locally advanced prostate cancer in our institution. PATIENTS AND METHODS: Three hundred and eight patients were treated between January 1990 and December 1996. Fifty-five of these were recruited for pT3 or pN1 tumors after radical prostatectomy. Neoadjuvant androgen deprivation was given in 106 patients. The treatment protocol consisted of a mixed photon/neutron irradiation in a two-to-three proportion, up to a total equivalent dose of 66 Gy (assuming a clinical RBE value of 2.8). Pre- and post-treatment PSA determinations were available in practically all cases. Study endpoints were overall survival (OAS) and progression-free survival (PFS). The Cox proportional hazard regression model was used to investigate the prognostic value of baseline characteristics on survival and progression-free survival were a progression was defined as local, regional, metastatic or biological progression. Mean age was 69 years (49-86); mean pretreatment PSA was 15 (0.5-330) in all patients and 14 (0.5-160) in those receiving neoadjuvant hormonotherapy; seven patients only had an initial PSA < or = 4 ng/mL; 15% were T1, 46% were T2, 28% were T3 or pT3 and 4% were T4 (7% unspecified); WHO grade of differentiation was I in 38%, II in 38% and III in 14% (5% unspecified). RESULTS: The median follow-up was 2.8 years (0-7.8). Five-year overall survival (OAS) was 79% (95% CI: 71-87%) and 5-year progression-free survival (PFS) was 64% (95% CI: 54-74%) for the entire series. PFS in patients with an initial PSA > or = 20 ng/mL was the same. PFS could be predicted by two optimal Cox regression models, one including histological grade (p = 0.003) and initial PSA (p = 0.0009) as cofactors, the other including histological grade (p = 0.003) and T stage (p = 0.02). The main prognostic factors for overall survival were PSA and age. Biological responses with PSA < 1.5 ng/mL, < 1 ng/mL and < 0.5 ng/mL at any time after treatment were documented in 70%, 61% and 47% of the patients, respectively. CONCLUSION: Five-year OAS was 79%, PFS was 64%, and biological response was 70% for prostate cancer patients treated with mixed photon/neutron beams as applied at Louvain-la-Neuve, which are good results as compared with the literature. The usual prognostic factors were confirmed.

Rectal sequelae after conformal radiotherapy of prostate cancer: dose-volume histograms as predictive factors.

PURPOSE: To identify clinically relevant parameters predictive of late rectal bleeding derived from cumulative dose-volume histograms (DVHs) of the rectum after conformal radiotherapy of prostate cancer. MATERIALS AND METHODS: One hundred and nine patients treated with 3D conformal radiotherapy between 1/1994 and 1/1996 for localized prostate cancer (clinical stage T1-T3) were available for analysis. All patients received a total dose of 66 Gy/2 Gy per fraction (specified at the International Commission on Radiation Units and Measurements ICRU reference point). DVHs of the contoured rectum were analyzed by defining the absolute (aV) and relative (rV) rectum volume that received more than 30% (V30), 50% (V50), 70% (V70), 80% (V80), 90% (V90) and 100% (V100) of the prescribed dose. Additionally, a new aspect of DVH analysis was investigated by calculation of the area under the DVH-curve between several dose levels (area under the curve (AUC)-DVH). DVH-variables were correlated with radiation side effects evaluated in 3-6 months intervals and graded according to the EORTC/RTOG score. The median follow-up was 30 months (12-60 months). RESULTS: Univariate and multivariate stepwise Cox-Regression analysis including age, PTV, rectum size, rV100, rV90, rV80, rV70, rV50 rV30 and aV30 to aV100 were calculated. Late rectal bleeding (EORTC/RTOG grade 2) was significantly correlated with the percentage of rectum volume receiving > or = 90% of the prescribed dose (rV90) (P = 0.007) and inversely correlated in a significant way with the size of contoured rectum (P = 0.006) in multivariate analysis. In our series, a proportion of the rectum volume > or = 57% were included in the 90%-isodose (rV90 > or = 57%) in one half of the patients, with an actuarial incidence of 31% of late rectal bleeding at 3 years. In the other half of the patients, when rV90 < 57%, the 3-year actuarial incidence was 11% (P < 0.03). CONCLUSION: Our data demonstrate a dose-volume relationship at the reference dose of 60 Gy ( approximately 90% of the prescribed dose) with respect to late rectal toxicity. The rV90 seems to be the most useful and easily obtained parameter when comparing treatment plans to evaluate the risk of rectal morbidity.

Survey of the use of the ICRU 38 in recording and reporting cervical cancer brachytherapy.

BACKGROUND: A survey on the practice of reporting intracavitary cervix cancer brachytherapy (LDR and HDR) in clinical practice (CP) and in literature (LIT) was performed on the occasion of a workshop, 'ICRU 38: The Basis for a Revision', which took place at the Annual GEC ESTRO meeting in Naples in 1998. MATERIALS AND METHODS: The answers (n=85) to a specific questionnaire which had been sent to all ESTRO members (n=1600), were evaluated. In parallel, a systematic survey on the literature reporting cervix cancer brachytherapy since 1985 was performed using the MEDLINE database. The main recommendations for reporting as given in the ICRU 38 were addressed for both surveys: technique; total reference air kerma (TRAK); dose specification to the target volume '60 Gy reference volume', to organs at risk 'ICRU rectum and bladder point' and other reference points and time-dose pattern. In addition, some other items were investigated such as mg h, Point A, B, and in vivo dosimetry in bladder and rectum. RESULTS: Issues related to technique (source, machine and applicator type) and to time-dose pattern are reported in the majority of patients in CP and LIT. The same applies for the following parameters: Point A is indicated in 76% (LDR) to 89% (HDR) in CP, in 60% (LDR) to 96% (HDR) in LIT. Rectum and bladder ICRU points are recorded in 55% (HDR) to 90% (LDR) and 58% (HDR) to 84% (LDR), respectively, in CP. On the other hand, TRAK is given in 14% (HDR) to 43% (LDR) in CP, in 0% (HDR) to 10% (LDR) in LIT. '60 Gy reference volume' is recorded in 18% (HDR) to 51% (LDR) in CP, in 0% (HDR) to 17% (LDR) in LIT. Rectum and bladder ICRU points are reported in 18% (LDR) to 28% (HDR) and 14% (HDR) to 29% (LDR), respectively, in LIT. Other reference points and in vivo dosimetry measurements are given in a low percentage. Dose rate and overall treatment time is reported in 10-44%. CONCLUSION: Recording and reporting in CP and in LIT meets the recommendations as given in ICRU 38 to different degrees. Specific items such as TRAK and the 'Reference volume' have only limited penetration into CP and LIT, which applies in particular to centers using HDR brachytherapy. The discrepancies between CP and LIT may be due to the well-known delay between change in CP and its translation into LIT. In order to arrive at a more common language for the better exchange of clinical results, it seems to be necessary to adapt some terms and recommendations. In particular, comprehensive concepts are needed for reporting dose to points and volumes in the target and in critical organs, according to the new potential from imaging and computer technology and from modern radiobiological insights, bridging the gap between LDR and HDR brachytherapy.

Comparison of radiography- and computed tomography-based treatment planning in cervix cancer in brachytherapy with specific attention to some quality assurance aspects.

INTRODUCTION: A modern approach in treatment planning for cervix carcinoma is based on a series of computed tomography (CT) sections and 3D dose computation. When these techniques were not yet available, dose evaluation was based on orthogonal radiographs. The CT based planning provides information on target and organ volumes and dose-volume histograms. The radiography based planning provides only dimensions and doses at selected points. The aim of the presented study is to correlate the information obtained with the two approaches for high dose-rate (HDR) brachytherapy of cervix carcinoma. METHODS: For the study 28 patients with 35 applications receiving HDR treatment with Ir-192 were investigated. The planning system PLATO (Nucletron) was used. The different aspects of available data, results and inaccuracies regarding quality assurance were looked at. RESULTS: From the CT based planning, the volume, location and dose-volume histograms were calculated for the CTV, rectum and bladder. From the radiography-based planning, the dose to point A (prescription), point B, rectum and bladder ICRU reference points [14], points related to the bony structures could be evaluated as well as volumes receiving different dose levels. These two sets of information were compared and following mean values derived. For a dose prescription of 7 Gy at point A, as an average, 83% (44 cm(3)) of the clinical target volume (CTV) receives at least 7 Gy. The mean dose at the rectum ICRU reference point is 4.3 Gy, and 12% (9 cm(3)) of the rectum is encompassed by the 4.3 Gy isodose. The mean dose at the bladder ICRU reference point is 5.8 Gy, and 8% (16 cm(3)) of the bladder is encompassed by the 5.8 Gy isodose. The maximum dose to the rectum is 1.5 times higher than the dose at the ICRU reference point, and for the bladder 1.4 times higher. Uncertainties caused by the reconstruction of the applicator and merging of isodoses could be evaluated. DISCUSSION: The subdivision of different approaches and the transfer from point doses to volumes in treatment planning is possible and practical for the treatment of cervix carcinoma in brachytherapy.

Endoscopic scoring of late rectal mucosal damage after conformal radiotherapy for prostatic carcinoma.

PURPOSE: To describe rectal mucosal damage in an endoscopic study after conformal radiotherapy of prostate cancer and to correlate this with clinical outcome. MATERIALS AND METHODS: Flexible rectosigmoidoscopy was performed on 44 patients who voluntarily accepted the examination. The median follow-up was 29 months (20-41 months) after 3-D-planned conformal radiotherapy of prostate cancer (66 Gy at the ICRU Reference point, 2 Gy per fraction). To enable a systematic topographic description of endoscopic findings the rectum was divided into four sections. Additionally we differentiated between anterior, posterior, right and left lateral rectal wall. Due to the lack of an existing valid graduation system for radiation induced proctitis, we introduced a six-scaled rectoscopy score for describing and reporting endoscopic findings based on the standardization of the endoscopic terminology published by the ESGE (European Society for Gastrointestinal Endoscopy). Endoscopic findings were compared to the EORTC/RTOG morbidity score. In addition, since 3-D dose distribution of organs at risks was available, a correlation could be made between the location of the rectal lesions and the absorbed dose at that level. RESULTS: In general, endoscopic findings increased from the proximal rectum to the anorectal transition, as well as from the posterior to the anterior rectum wall. Telangiectasia grade 1 and 2 were observed at the whole circumference, only telangiectasia grade 3 were limited to the high dose region at the anterior rectum wall. Similar results were found for congested mucosa (reddening and edematous mucosa). Correlation with symptoms, 7/9 patients who suffered from intermittent rectal bleeding (EORTC/RTOG grade 2) had multiple telangiectasia grade 2-3 and/or congested mucosa grade 3 and microulcerations. However, the same extent of mucosal damage (rectoscopy score 2-3) was found in seven out of 35 patients who have never developed a period of macroscopic rectal bleeding. CONCLUSION: Rectoscopy offers the possibility of detecting signs of tissue dysfunction below the level of subjective symptoms. Systematic analytic examinations such as rectoscopy, in addition to clinical examinations, as already foreseen in the LENT-SOMA-score, will be necessary due to the fact that even telangiectatic lesions have been observed for asymptomatic patients. For the opportunity of sharing and comparing data collected from endoscopy after radiotherapy a graduation system as proposed based on a standardisation of the endoscopic terminology will be necessary.

A consistent set of neutron kerma coefficients from thermal to 150 MeV for biologically important materials.

Neutron cross sections for nonelastic and elastic reactions on a range of elements have been evaluated for incident energies up to 150 MeV. These cross sections agree well with experimental cross section data for charged-particle production as well as neutron and photon production. Therefore they can be used to determine kerma coefficients for calculations of energy deposition by neutrons in matter. Methods used to evaluate the neutron cross sections above 20 MeV, using nuclear model calculations and experimental data, are described. Below 20 MeV, the evaluated cross sections from the ENDF/B-VI library are adopted. Comparisons are shown between the evaluated charged-particle production cross sections and measured data. Kerma coefficients are derived from the neutron cross sections, for major isotopes of H, C, N, O, Al, Si, P, Ca, Fe, Cu, W, Pb, and for ICRU-muscle, A-150 tissue-equivalent plastic, and other compounds important for treatment planning and dosimetry. Numerous comparisons are made between our kerma coefficients and experimental kerma coefficient data, to validate our results, and agreement is found to be good. An important quantity in neutron dosimetry is the kerma coefficient ratio of ICRU-muscle to A-150 plastic. When this ratio is calculated from our kerma coefficient data, and averaged over the neutron energy spectra for higher-energy clinical therapy beams [three p (68) + Be beams, and a d (48.5) + Be beam], a value of 0.94 +/- 0.03 is obtained. Kerma ratios for water to A-150 plastic, and carbon to oxygen, are also compared with measurements where available.

Nuclear data for radiotherapy: presentation of a new ICRU report and IAEA initiatives.

An ICRU report entitled "Nuclear Data for Neutron and Proton Radiotherapy and for Radiation Protection" is in preparation. The present paper presents an overview of this report, along with examples of some of the results obtained for evaluated nuclear cross sections and kerma coefficients. These cross sections are evaluated using a combination of measured data and the GNASH nuclear model code for elements of importance for biological, dosimetric, beam modification and shielding purposes. In the case of hydrogen both R-matrix and phase-shift scattering theories are used. In the report neutron cross sections and kerma coefficients will be presented up to 150 MeV and proton cross sections up to 250 MeV. An IAEA Consultants' Meeting was also convened to examine the "Status of Nuclear Data needed for Radiation Therapy and Existing Data Development Activities in Member States". Recommendations were made regarding future endeavours.

RBE, reference RBE and clinical RBE: applications of these concepts in hadron therapy.

Introduction of heavy particles (hadrons) into radiation therapy aims at improving the physical selectivity of the irradiation (e.g. proton beams), or the radiobiological differential effect (e.g. fast neutrons), or both (e.g. heavy-ion beams). Each of these new therapy modalities requires several types of information before prescribing safely the doses to patients, as well as for recording and reporting the treatments: (i) absorbed dose measured in a homogeneous phantom in reference conditions; (ii) dose distribution computed at the level of the target volume(s) and the normal tissues at risk; (iii) radiation quality from which a RBE evaluation could be predicted and (iv) RBE measured on biological systems or derived from clinical observation. In hadron therapy, the RBE of the different beams raises specific problems. For fast neutrons, the RBE varies within wide limits (about 2 to 5) depending on the neutron energy spectrum, dose, and biological system. For protons, the RBE values range between smaller limits (about 1.0 to 1.2). A clinical benefit can thus not be expected from RBE differences. However, the proton RBE problem cannot be ignored since dose differences of about 5% can be detected clinically in some cases. The situation is most complex with heavy ions since RBE variations are at least as large as for fast neutrons, as a function of particle type and energy, dose and biological system. In addition, RBE varies with depth. Radiation quality thus has to be taken into account when prescribing and reporting a treatment. This can be done in different ways: (a) description of the method of beam production; (b) computed LET spectra and/or measured microdosimetric spectra at the points clinically relevant; (c) RBE determination. The most relevant RBE data are those obtained for late tolerance of normal tissues at 2 Gy per fraction ("reference RBE"). The "clinical RBE" selected by the radiation oncologist when prescribing the treatment will be close to the reference RBE, but other factors (such as heterogeneity in dose distribution) may influence the selection of the clinical RBE. Combination of microdosimetric data and experimental RBE values improves the confidence in both sets of data.