Planning Benchmark Study for Stereotactic Body Radiation Therapy of Pancreas Carcinomas with Simultaneously Integrated Boost and Protection: Results of the DEGRO/DGMP Working Group on Stereotactic Radiation Therapy and Radiosurgery.

PURPOSE/OBJECTIVE: The proximity or overlap of PTV and OAR poses a major challenge in SBRT of pancreatic cancer (PACA). This international treatment planning benchmark study investigates whether Simultaneously Integrated Boost (SIB) and Protection (SIP) concepts in PACA SBRT can lead to improved and harmonized plan quality. MATERIALS/METHODS: A multiparametric specification of desired target doses (GTVD50%, GTVD99%, PTVD95%, PTV0.5cc) with two prescription doses of GTVD50%=5×9.2Gy (46Gy) and GTVD50%=8×8.25Gy (66Gy) and OAR limits were distributed with planning CT and contours from 3 PACA patients. In phase 1, plans were ranked using a scoring system for comparison of trade-offs between GTV/PTV and OAR. In phase 2, re-planning was performed for the most challenging case and prescription with dedicated SIB and SIP contours provided for optimization after group discussion. RESULTS: For all 3 cases and both phases combined, 292 plans were generated from 42 institutions in 5 countries using commonly available treatment planning systems. The GTVD50% prescription was performed by only 76% and 74% of planners within 2% for 5 and 8 fractions, respectively. The GTVD99% goal was mostly reached, while the balance between OAR and target dose showed initial SIB/SIP-like optimization strategies in about 50% of plans. For plan ranking, 149 and 217 score penalties were given for 5 and 8 fractions, pointing to improvement possibilities. For phase 2, the GTVD50% prescription was performed by 95% of planners within 2% and GTVD99% as well as OAR doses were better harmonized with notable less score penalties. Fourteen of 19 planners improved their plan rank, 9 of them by at least 2 ranks. CONCLUSION: Dedicated SIB/SIP concepts in combination with multiparametric prescriptions and constraints can lead to overall harmonized and high treatment plan quality for PACA SBRT. Standardized SIB/SIP treatment planning in multicenter clinical trials appears feasible after group consensus and training.

Improving dose delivery accuracy with EPID in vivo dosimetry: results from a multicenter study.

PURPOSE: To investigate critical aspects and effectiveness of in vivo dosimetry (IVD) tests obtained by an electronic portal imaging device (EPID) in a multicenter and multisystem context. MATERIALS AND METHODS: Eight centers with three commercial systems-SoftDiso (SD, Best Medical Italy, Chianciano, Italy), Dosimetry Check (DC, Math Resolution, LCC), and PerFRACTION (PF, Sun Nuclear Corporation, SNC, Melbourne, FL)-collected IVD results for a total of 2002 patients and 32,276 tests. Data are summarized for IVD software, radiotherapy technique, and anatomical site. Every center reported the number of patients and tests analyzed, and the percentage of tests outside of the tolerance level (OTL%). OTL% was categorized as being due to incorrect patient setup, incorrect use of immobilization devices, incorrect dose computation, anatomical variations, and unknown causes. RESULTS: The three systems use different approaches and customized alert indices, based on local protocols. For Volumetric Modulated Arc Therapy (VMAT) treatments OTL% mean values were up to 8.9% for SD, 18.0% for DC, and 16.0% for PF. Errors due to "anatomical variations" for head and neck were up to 9.0% for SD and DC and 8.0% for PF systems, while for abdomen and pelvis/prostate treatments were up to 9%, 17.0%, and 9.0% for SD, DC, and PF, respectively. The comparison among techniques gave 3% for Stereotactic Body Radiation Therapy, 7.0% (range 4.7-8.9%) for VMAT, 10.4% (range 7.0-12.2%) for Intensity Modulated Radiation Therapy, and 13.2% (range 8.8-21.0%) for 3D Conformal Radiation Therapy. CONCLUSION: The results obtained with different IVD software and among centers were consistent and showed an acceptable homogeneity. EPID IVD was effective in intercepting important errors.

Hippocampal sparing in stereotactic radiotherapy for brain metastases: To contour or not contour the hippocampus?

PURPOSE: The aim of our study was to evaluate hippocampal irradiation in patients treated with fractionated stereotactic brain radiotherapy. PATIENTS AND METHODS: Retrospective hippocampal dosimetric analysis performed on 22 patients with one to four brain metastases treated with fractionated stereotactic radiotherapy using volumetric intensity-modulated arc therapy. Original plans did not include hippocampus as avoidance structure in optimization criteria; hippocampus was retrospectively delineated on magnetic resonance coregistered with planning CT and using as reference the RTOG 0933 atlas. Hippocampus was defined both as a single and as pair organ. Constraints analysed were: Dmax<16Gy, D40%<7.3Gy, D100%=Dmin<9Gy. Assuming a α/ß ratio of 2Gy, biologically equivalent dose in 2Gy fractions was calculated. Hippocampal-sparing plans were developed in cases where hippocampal constraints were not respected in the original plan. RESULTS: Among constraints analysed Dmax and D40% have been exceeded in ten out of 22 cases. The constraints were not respected in patients with more than one metastatic lesion and in three patients with only one lesion. Considering all exceeded constraints values in non-hippocampal sparing plans, the 50% of them was respected after replanning. No significant differences were found among conformity and homogeneity index between non-hippocampal sparing and hippocampal sparing plans. CONCLUSION: Volumetric intensity-modulated arc therapy hippocampal sparing plans significantly decreases dose to hippocampus assuring an equal target coverage and organs at risk avoiding.

A novel synthetic single crystal diamond device for in vivo dosimetry.

PURPOSE: Aim of the present work is to evaluate the synthetic single crystal diamond Schottky photodiode developed at the laboratories of "Tor Vergata" University in Rome in a new dosimeter configuration specifically designed for offline wireless in vivo dosimetry (IVD) applications. METHODS: The new diamond based dosimeter, single crystal diamond detector (SCDD-iv), consists of a small unwired detector and a small external reading unit that can be connected to commercial electrometers for getting the detector readout after irradiation. Two nominally identical SCDD-iv dosimeter prototypes were fabricated and tested. A basic dosimetric characterization of detector performances relevant for IVD application was performed under irradiation with (60)Co and 6 MV photon beams. Preirradiation procedure, response stability, short and long term reproducibility, leakage charge, fading effect, linearity with dose, dose rate dependence, temperature dependence, and angular response were investigated. RESULTS: The SCDD-iv is simple, with no cables linked to the patient and the readout is immediate. The range of response with dose has been tested from 1 up to 12 Gy; the reading is independent of the accumulated dose and dose rate independent in the range between about 0.5 and 5 Gy/min; its temperature dependence is within 0.5% between 25 and 38 °C, and its directional dependence is within 2% from 0° to 90°. The combined relative standard uncertainty of absorbed dose to water measurements is estimated lower than the tolerance and action level of 5%. CONCLUSIONS: The reported results indicate the proposed novel offline dosimeter based on a synthetic single crystal diamond Schottky photodiode as a promising candidate for in vivo dosimetry applications with photon beams.

Characterization of a microDiamond detector in high-dose-per-pulse electron beams for intra operative radiation therapy.

PURPOSE: To characterize a synthetic diamond dosimeter (PTW Freiburg microDiamond 60019) in high dose-per-pulse electron beams produced by an Intra Operative Radiation Therapy (IORT) dedicated accelerator. METHODS: The dosimetric properties of the microDiamond were assessed under 6, 8 and 9 MeV electron beams by a NOVAC11 mobile accelerator (Sordina IORT Technologies S.p.A.). The characterization was carried out with dose-per-pulse ranging from 26 to 105 mGy per pulse. The microDiamond performance was compared with an Advanced Markus ionization chamber and a PTW silicon diode E in terms of dose linearity, percentage depth dose (PDD) curves, beam profiles and output factors. RESULTS: A good linearity of the microDiamond response was verified in the dose range from 0.2 Gy to 28 Gy. A sensitivity of 1.29 nC/Gy was measured under IORT electron beams, resulting within 1% with respect to the one obtained in reference condition under (60)Co gamma irradiation. PDD measurements were found in agreement with the ones by the reference dosimeters, with differences in R50 values below 0.3 mm. Profile measurements evidenced a high spatial resolution of the microDiamond, slightly worse than the one of the silicon diode. The penumbra widths measured by the microDiamond resulted approximately 0.5 mm larger than the ones by the Silicon diode. Output factors measured by the microDiamond were found within 2% with those obtained by the Advanced Markus down to 3 cm diameter field sizes. CONCLUSIONS: The microDiamond dosimeter was demonstrated to be suitable for precise dosimetry in IORT applications under high dose-per-pulse conditions.

Radiotherapy electron beams collimated by small tubular applicators: characterization by silicon and diamond diodes.

High-energy electron beams generated by linear accelerators, typically in the range 6 to 20 MeV, are used in small field sizes for radiotherapy of localized superficial tumors. Unshielded silicon diodes (Si-D) are commonly considered suitable detectors for relative dose measurements in small electron fields due to their high spatial resolution. Recently, a novel synthetic single crystal diamond diode (SCDD) showed suitable properties for standard electron beams and small photon beams dosimetry. The aim of the present study is twofold: to characterize 6 to 15 MeV small electron beams shaped by using commercial tubular applicators with 2, 3, 4 and 5 cm diameter and to assess the dosimetric performance under such irradiation conditions of the novel SCDD dosimeter by comparison with commercially available dosimeters, namely a Si-D and a plane­parallel ionization chamber. Percentage depth dose curves, beam profiles and output factors (OFs) were measured. A good agreement among the dosimeters was observed in all of the performed measurements. As for the tubular applicators, two main effects were evidenced: (i) OFs larger than unity were measured for a number of field sizes and energies, with values up to about 1.3, that is an output 30% greater than that obtained at the 10 × 10 cm2 reference field; (ii) for each diameter of the tubular applicator a noticeable increase of the OF values was observed with increasing beam energy, up to about 100% in the case of the smaller applicator. This OF behavior is remarkably different from what typically observed for small blocked fields having the same size and energy as those used in this study. OFs for tubular applicators depend considerably on the field size, so interpolation is unadvisable to predict the linear accelerator output for such applicators whereas reliable high-resolution detectors, as the silicon and diamond diodes used in this work allow OF measurements with uncertainties of about 1%.

Fatigue in patients undergoing radiation therapy: an observational study.

AIM: Fatigue can be defined as an unpleasant feeling of tiredness, weakness and lack of energy. It is found in about 80% of the patients receiving radiation therapy and has a significant impact on quality of life. The aim of this paper was to assess the frequency, severity and changes of fatigue before, during and after administration of a nutraceutical (mixture of whey protein with an high biological value, with an high content in native cysteine, albumin and lactoferrin in patients undergoing treatment for breast and prostate cancer. METHODS: Thirty patients (20 breast and 10 prostate ones) were enrolled in our test and they received a questionnaire about Fatigue developed by the University of Texas, MD Anderson Cancer Center, 1999. The patients who achieved a score between 4 and 6 were administered the nutraceutical (Prother) at a dose of 20 g / day for the first 10 days of radiation treatment and then 10 g/day for the following 20 days without considering the terms of the radiation oncology treatment [corrected]. Each patient was reassessed using the same Fatigue test after 10 and 30 days from the start of the administration of nutraceutical. We enrolled 30 control patients who did not receive Prother. RESULTS: The results showed the effectiveness of Prother in all patients with moderate-to-mild fatigue. CONCLUSION: The administration of Prother has therefore been effective in terms of both improving the compliance of the radiation treatment and the quality of life.

Characterization of a synthetic single crystal diamond Schottky diode for radiotherapy electron beam dosimetry.

PURPOSE: To investigate the dosimetric properties of synthetic single crystal diamond based Schottky diodes under irradiation with therapeutic electron beams from linear accelerators. METHODS: A single crystal diamond detector was fabricated and tested under 6, 8, 10, 12, and 15 MeV electron beams. The detector performances were evaluated using three types of commercial detectors as reference dosimeters: an Advanced Markus plane parallel ionization chamber, a Semiflex cylindrical ionization chamber, and a p-type silicon detector. Preirradiation, linearity with dose, dose rate dependence, output factors, lateral field profiles, and percentage depth dose profiles were investigated and discussed. RESULTS: During preirradiation the diamond detector signal shows a weak decrease within 0.7% with respect to the plateau value and a final signal stability of 0.1% (1σ) is observed after about 5 Gy. A good linear behavior of the detector response as a function of the delivered dose is observed with deviations below ±0.3% in the dose range from 0.02 to 10 Gy. In addition, the detector response is dose rate independent, with deviations below 0.3% in the investigated dose rate range from 0.17 to 5.45 Gy∕min. Percentage depth dose curves obtained from the diamond detector are in good agreement with the ones from the reference dosimeters. Lateral beam profile measurements show an overall good agreement among detectors, taking into account their respective geometrical features. The spatial resolution of solid state detectors is confirmed to be better than that of ionization chambers, being the one from the diamond detector comparable to that of the silicon diode. A good agreement within experimental uncertainties was also found in terms of output factor measurements between the diamond detector and reference dosimeters. CONCLUSIONS: The observed dosimetric properties indicate that the tested diamond detector is a suitable candidate for clinical electron beam dosimetry.

Preliminary experience of a predictive model to define rectal volume and rectal dose during the treatment of prostate cancer.

OBJECTIVES: The aim of this study was to define a method to evaluate the total dose delivered to the rectum during the whole treatment course in six patients undergoing irradiation for prostate cancer using an offline definition of organ motion with images from a cone beam CT (CBCT) scanner available on a commercial linear accelerator. METHODS: Patient set-up was verified using a volumetric three-dimensional CBCT scanner; 9-14 CBCT scans were obtained for each patient. Images were transferred to a commercial treatment planning system for offline organ motion analysis. The shape of the rectums were used to obtain a mean dose-volume histogram (), which was the average of the DVHs of the rectums as they appeared in each verification CBCT. A geometric model of an average rectum (AR) was produced using the rectal contours delineated on the CBCT scans (DVH(AR)). To check whether the first week of treatment was representative of the whole treatment course, we evaluated the DVHs related to only the first five CBCT scans ( and DVH(AR5)). Finally, the influence of a dietary protocol on the goodness of our results was considered. RESULTS: In all six patients the original rectal DVH for the planning CT scan showed higher values than all DVHs. CONCLUSION: Although the application of the model to a larger set of patients is necessary to confirm this trend, reconstruction of a representative volume of the rectum throughout the entire treatment course seems feasible.

[Assessment of exposure to laser radiation in research laboratories]. / Valutazione dell'esposizione alla radiazione laser nei laboratori di ricerca.

The problem of laser safety is now topical due to the wide use of laser systems in different working environments. The program of prevention and protection prescribed by law 626/94 gives general rules for the elimination (where possible) and/or reduction of risk factors. For this purpose, it is important to determine the parameters that characterize such risks. The Maximum Permissible Exposure (MPE) and the Nominal Ocular Hazard Distance (NOHD) are the most important parameters of laser safety. The evaluation of these parameters requires a detailed knowledge of the standards and of the various techniques which are necessary to measure them. In particular, the MPE parameters are obtained by CEI EN 60825-1 standard in relation to wavelength and emission duration of the investigated laser. Exposure to laser radiation is usually measured in terms of irradiance (W/m2) or radiant exposure (J/m2). The experimental values of irradiance must be compared with the MPE parameters obtained by safety standards. When the values of irradiance exceed the MPE parameters then the NOHD values must to be calculated. The aim of this paper is to offer a general view of the methods for measuring the above-mentioned parameters for the laser sources that are most widely used in research environments and to compare such parameters with those recommended by safety standards. Our results indicate that for almost all the laser sources analysed, the measured exposure values were greater than the MPE recommended by standards, both for eyes and skin. High values of NOHD indicate that it is necessary to use eye protection, beam stops or attenuators at the end of the useful beam path in normal working conditions and especially in research laboratories in which these conditions can often change.

[Epidemiological study of healthy carriers of Australia antigen. Analysis of contagiousness, and mechanism of spread of the infection (author's transl)]. / Estudio epidemiológico de los portadores sanos de antíaeno Australia. Análisis de su infecto-contagiosidad y mecanismo de aparición de nuevos casos.

Epidemiological studies in healthy carriers of HB Ag show variable results that might depend on the geographical area, ethnic group, and socio-economic level analyzed. For that reason an study was undertaken in the Spanish population with the purpose of analysing contagiousness of healthy carriers and mechanism of spread of the infection. The incidence of HB Ag and HB Ab was determined by radioimmunoassay in 211 relatives of 76 healthy carriers; all members of the family could be studied in 51 cases. The results were compared to those of a sizeable sample of the normal population. The overall incidence of HB Ag (13.1 %), and of HB Ab (18.9 %) in the probands was significantly higher than in the normal population (0.8 %, and 9 %, respectively). The distribution of new cases of HB Ag positivity in the 51 families in which the members could be studied demonstrated a significantly higher frequency in children of a carrier mother (28.9 %) than in those of a carrier father (10.8 %). In conclusion, the contagiousness of healthy carriers for their families can not be disregarded. It is likely that the mechanism of spread of the infection depends on a multifactorial inheritance of the genetic alteration of the selective immunologic response to the HB Ag, compounded by environmental factors.

[Persistent and asymptomatic carriers of Australia antigen. A method for the evaluation of big series (author's transl)]. / Portadores persistentes y asintomáticos de antígeno Australia. Sistemática para la valoración de series amplias.

The existence of an increasing number of apparently healthy carriers of the HBsAg demands a specific assisting attitude which must be highly reliable without increasing health care expenses. With that purpose, 129 asymptomatic carriers without prior history of jaundice and/or alcohol abuse were studied. The following discriminant criteria were used: hepatomegaly, other physical evidence of liver disease, hypertransaminasemia, and sulfobromophthalein retention. The carrier was defined as healthy after two consecutive examinations disclosing no abnormalities at intervals of six months, which occurred in 108 patients (84 %). No patient underwent liver biopsy, but the examination was still normal after two years in all cases. The presence of one or more abnormal findings was an indication for liver biopsy in 21 patients (16 %), and the procedure was accepted by 11 (52 %). The efficiency of the selection method was evaluated according to the histologic findings. The most useful criteria were hypertransaminasemia and sulfobromophthalein retention, in this order.