Radiotherapy combined with deep regional hyperthermia in elderly and frail patients with muscle-invasive bladder cancer: quality analysis of hyperthermia and impact on clinical results.

Purpose: Radiotherapy (RT) in combination with deep regional hyperthermia (HT) after transurethral removal of bladder tumor (TURBT) can be offered to elderly and frail patients with muscle-invasive bladder cancer (MIBC).Methods: In total, 21 patients (mean age 84 years) with unifocal or multifocal MIBC received radiation to a dose of 48-50 Gy/16-20 fractions with weekly HT. The primary endpoint was the variation in temperature metrics, thermal dose expressed as cumulative equivalent minutes at 43 °C when the measured temperature is T90 (CEM43T90) and net power applied in target volume per each HT session. Secondary endpoints were three-year overall survival (OS), disease-free survival (DFS), local progression-free survival (LPFS) and toxicity.Results: The temperature metrics, CEM43T90, mean and maximum net power applied did not differ significantly among the HT sessions of the 21 patients. With a median follow-up of 65 months, 52% (95% CI 32-72%) of patients had died 3 years after treatment. The three-year DFS and LPFS rates were 62% (95%CI 41-79%) and 81% (95%CI 60-92%), respectively. The three-year bladder preservation rate was 100%. Three out of four patients with local failure received a thermal dose CEM43T90 below a median of 2.4 min. The rates of acute and late grade-3 toxicities were 10% and 14%, respectively.Conclusion: The reproducibility of HT parameters between sessions was high. A moderately high CEM43T90 (> 2.4 min) for each HT session seems to be preferable for local control. RT combined with HT is a promising organ-preservation therapy for elderly and frail MIBC patients.

Real World Analysis of Quality of Life and Toxicity in Cancer Patients Treated with Hyperthermia Combined with Radio(chemo)therapy.

Hyperthermia (HT) in combination with radio(chemo)therapy (RCT) is a well-established cancer treatment strategy. This report analyses the quality of life (QoL), toxicity and survival outcomes in patients with different tumor entities who received HT in combination with RCT. The primary endpoint of this study was the assessment of QoL scale items 3 and 12 months after treatment in patients who were treated with palliative intent and curative intent, respectively. The secondary endpoints of this study were acute toxicities, 1-year overall survival (OS), and local progression-free survival (LPFS). Patients treated with curative intent experienced significant improvement in emotional functioning (EF), social functioning (SF), financial difficulties (FI) and insomnia (SL) 12 months after treatment. Patients had significantly improved FI and pain (PA) three months after palliative treatment. Acute toxicity of grade 3 or more was 26% during treatment and 4% after three months. The 1-year OS rates were 90% (95% CI: 79-96%) and 44% (95% CI: 31-59%) for patients treated with curative and palliative RCT combined with HT, respectively. Moreover, the 1-year LPFS rates were 94% (95% CI: 84-98%) for patients treated with curative intent and 64% (95% CI: 50-77%) for palliative patients. In summary, combined RCT and HT stabilized or improved QoL scale items for both curative and palliative indications.

A patterns of care analysis of hyperthermia in combination with radio(chemo)therapy or chemotherapy in European clinical centers.

PURPOSE: The combination of hyperthermia (HT) with radio(chemo)therapy or chemotherapy (CT) is an established treatment strategy for specific indications. Its application in routine clinical practice in Europe depends on regulatory and local conditions. We conducted a survey among European clinical centers to determine current practice of HT. METHODS: A questionnaire with 22 questions was sent to 24 European HT centers. The questions were divided into two main categories. The first category assessed how many patients are treated with HT in combination with radio(chemo)therapy or CT for specific indications per year. The second category addressed which hyperthermia parameters are recorded. Analysis was performed using descriptive methods. RESULTS: The response rate was 71% (17/24) and 16 centers were included in this evaluation. Annually, these 16 centers treat approximately 637 patients using HT in combination with radio(chemo)therapy or CT. On average, 34% (range: 3-100%) of patients are treated in clinical study protocols. Temperature readings and the time interval between HT and radio(chemo)therapy or CT are recorded in 13 (81%) and 9 (56%) centers, respectively. The thermal dose quality parameter "cumulative equivalent minutes at 43 °C" (CEM43°C) is only evaluated in five (31%) centers for each HT session. With regard to treatment sequence, 8 (50%) centers administer HT before radio(chemo)therapy and the other 8 in the reverse order. CONCLUSION: There is a significant heterogeneity among European HT centers as to the indications treated and the recording of thermometric parameters. More evidence from clinical studies is necessary to achieve standardization of HT practice.

Tetramodal therapy with transurethral resection followed by chemoradiation in combination with hyperthermia for muscle-invasive bladder cancer: early results of a multicenter phase IIB study.

BACKGROUND: Transurethral resection of bladder tumor (TUR-BT) followed by chemoradiation (CRT) is a valid treatment option for patients with muscle-invasive bladder cancer (MIBC). This study aimed to investigate the efficacy of a tetramodal approach with additional regional hyperthermia (RHT). METHODS: Patients with stages T2-4 MIBC were recruited at two institutions. Treatment consisted of TUR-BT followed by radiotherapy at doses of 57-58.2 Gy with concurrent weekly platinum-based chemotherapy and weekly deep RHT (41-43 °C, 60 min) within two hours of radiotherapy. The primary endpoint was a complete response six weeks after the end of treatment. Further endpoints were cystectomy-free rate, progression-free survival (PFS), local recurrence-free survival (LRFS), overall survival (OS) and toxicity. Quality of life (QoL) was assessed at follow-up using the EORTC-QLQ-C30 and QLQ-BM30 questionnaires. Due to slow accrual, an interim analysis was performed after the first stage of the two-stage design. RESULTS: Altogether 27 patients were included in the first stage, of these 21 patients with a median age of 73 years were assessable. The complete response rate of evaluable patients six weeks after therapy was 93%. The 2-year cystectomy-free rate, PFS, LRFS and OS rates were 95%, 76%, 81% and 86%, respectively. Tetramodal treatment was well tolerated with acute and late G3-4 toxicities of 10% and 13%, respectively, and a tendency to improve symptom-related quality of life (QoL) one year after therapy. CONCLUSION: Tetramodal therapy of T2-T4 MIBC is promising with excellent local response, moderate toxicity and good QoL. This study deserves continuation into the second stage.

Clinical Evidence for Thermometric Parameters to Guide Hyperthermia Treatment.

Hyperthermia (HT) is a cancer treatment modality which targets malignant tissues by heating to 40-43 °C. In addition to its direct antitumor effects, HT potently sensitizes the tumor to radiotherapy (RT) and chemotherapy (CT), thereby enabling complete eradication of some tumor entities as shown in randomized clinical trials. Despite the proven efficacy of HT in combination with classic cancer treatments, there are limited international standards for the delivery of HT in the clinical setting. Consequently, there is a large variability in reported data on thermometric parameters, including the temperature obtained from multiple reference points, heating duration, thermal dose, time interval, and sequence between HT and other treatment modalities. Evidence from some clinical trials indicates that thermal dose, which correlates with heating time and temperature achieved, could be used as a predictive marker for treatment efficacy in future studies. Similarly, other thermometric parameters when chosen optimally are associated with increased antitumor efficacy. This review summarizes the existing clinical evidence for the prognostic and predictive role of the most important thermometric parameters to guide the combined treatment of RT and CT with HT. In conclusion, we call for the standardization of thermometric parameters and stress the importance for their validation in future prospective clinical studies.

Investigation of the effect of air gap size on the spatial resolution in proton- and helium radio- and tomography.

PURPOSE: Proton computed (transmission) tomography (pCT) refers to the process of imaging an object by letting protons pass through it, while measuring their energy after, and their position and (optionally) direction both before and after their traversal through that object. The so far experimental technique has potential to improve treatment planning of proton therapy by enabling the direct acquisition of a proton stopping power map of tissue, thus removing the need to obtain it by converting X-ray CT attenuation data and thereby eliminating uncertainties which arise in the mentioned conversion process. The image reconstruction in pCT requires accurate estimates of the proton trajectories. In experimental pCT detector setups where the direction of the protons is not measured, the air gap between the detector planes and the imaged object worsens the spatial resolution of the image obtained. In this work we determined the mean proton paths and the corresponding spatial uncertainty, taking into account the presence of the air gap. METHODS: We used Monte Carlo simulations of radiation transport to systematically investigate the effect of the air gap size between detector and patient on the spatial resolution of proton (ion) computed tomography for protons with an energy of 200MeV and 250MeV as well as for helium ions (He-4) with an energy of 798MeV. For the simulations we used TOPAS which itself is based on Geant4. RESULTS: For all particles, which are detected at the same entrance and exit coordinate, the average ion path and the corresponding standard deviation was computed. From this information, the dependence of the spatial resolution on the air gap size and the angular confusion of the particle beam was inferred. CONCLUSION: The presence of the airgap does not pose a problem for perfect fan beams. In realistic scenarios, where the initial angular confusion is around 5mrad and for typical air gap sizes up to 10cm, using an energy of 200MeV a spatial resolution of about 1.6mm can be achieved. Using protons with E=250MeV a spatial resolution of about 1.1mm and using helium ions (He-4) with E=798MeV even a spatial resolution below 0.7mm respectively is attainable.

Feasibility study of macroscopic simulations of nanodosimetric parameters for proton therapy.

PURPOSE: In view of the potential of treatment plan optimization based on nanodosimetric quantities, fast Monte Carlo methods for obtaining nanodosimetric quantities in macroscopic volumes are important. In this work, a "fast" method for obtaining nanodosimetric parameters from a clinical proton pencil beam in a macroscopic volume is compared with a slow and detailed method. Furthermore, the variations of these parameters, when obtained with the Monte Carlo codes TOPAS and NOREC, are investigated. METHODS: Monte Carlo track structure simulations of 1 keV-100 MeV protons and 12 eV-1 MeV electrons in a volume of 8 nm 3 liquid water provided us with an atlas of cluster size distributions. Two kinds of ionization cluster size distributions were recorded, counting all ionizations or only ionizations directly produced by the primary particle. The simulations of the proton pencil beam were performed in two different ways. A "fast" method where only the protons were simulated and a "slow and detailed" method where protons and electrons were simulated in order to obtain spectra at different depths. The obtained spectra were then convoluted with cluster size distributions. RESULTS: It was shown that the nanodosimetric quantity F 2 from the "fast" method is, depending on the location, between 43.6% and 63.6% smaller than the F 2 obtained by the "slow and detailed" method. However, it was also shown that variations of nanodosimetric quantities are even larger when the cluster size distributions of the electrons are simulated with the Monte Carlo code NOREC, that is, the cumulative F 2 probabilities obtained with NOREC were between 50.8% and 75.5% smaller than the F 2 probabilities obtained with TOPAS. CONCLUSIONS: As long as the uncertainties of different Monte Carlo codes are not improved, it is feasible to only simulate protons in a macroscopic volume. It must be noted, however, that the uncertainty is in the order of 100%.

Technical note: No increase in effective dose from half compared to full rotation pelvis cone beam CT.

PURPOSE: To image the abdomen of a patient with a gantry mounted imaging system of a linear accelerator, different cone beam computed tomography (CBCT) protocols are available. The whole-body dose of a full rotation abdomen CBCT and a half rotation CBCT was compared. In our clinic, both CBCT protocols are used in daily routine work. METHODS: With an adult anthropomorphic Alderson phantom, the whole-body dose per CBCT scan was measured with thermoluminescence dosimeters. The half rotation CBCT was applied such that the gantry mounted X-ray source rotated around the right side of the phantom. The 183 measurement locations covered all ICRP recommended critical organs (except the gonads). The effective dose was calculated with the mean organ dose and the corresponding tissue weighting factors. A point-by-point dose comparison of both protocols was conducted. RESULTS: The effective dose was 5.4 mSv ±5% and 5.0 mSv ±5% (estimated type B 1σ) for the full and the half rotation CBCT respectively. There was no significant difference (α = 0.05) in the effective dose within the precision of the measurement (1σ = 5%). The half rotation CBCT displayed an inhomogeneous dose distribution in a transversal phantom slice in contrast with the full rotation CBCT. In the imaging region, the mean dose was (20.5 ± 3.4) mGy and (19.2 ± 7.4) mGy (measured type A 1σ) for the full and the half rotation CBCT respectively. CONCLUSION: The half compared to the full rotation CBCT displays a smaller field-of-view in a transversal slice and no significant difference in the effective dose. Hence, the full rotation CBCT is favorable compared to the half rotation CBCT. However, by using the half rotation protocol, critical volumes in the patient can be spared compared to the full rotation protocol.

Technical Note: Comparison of peripheral patient dose from MR-guided 60 Co therapy and 6 MV linear accelerator IGRT.

PURPOSE: The use of X-ray imaging in radiation therapy can give a substantial dose to the patient. A Cobalt machine combined with an magnetic resonance imaging (MRI) was recently introduced to clinical work. One positive aspect of using non-ionizing imaging devices is the reduction of the patient exposure. The purpose of this study was to quantify the difference in out-of-field dose to the patient between the image guided radiation therapy (IGRT) treatment applied with a linear accelerator with cone beam CT (CBCT) equipment and a Cobalt machine combined with an MRI. METHODS: The treatment of a rhabdomyosarcoma in the prostate was planned and irradiated using different modalities and radiation therapy machines. The whole-body dose was measured for a 3D-conformal radiation therapy (3DCRT), an intensity-modulated radiation therapy (IMRT), and a volumetric-modulated arc therapy plan applied with a conventional linear accelerator operated at 6 MV beam energy. Additionally, the dose of an IMRT plan applied with a 60 Co machine combined with an MRI was measured. Furthermore, the dose of one CBCT scan using the linear accelerator's on-board imaging system was determined. The 3D dose measurements were performed in an anthropomorphic phantom containing 168 slots for thermoluminescence dosimeters (TLDs). A combination of LiF:Mg,Ti (TLD100) and LiF:Mg,Cu,P (TLD100H) was used to accurately determine the in- and out-of-field dose. The plans were rescaled to different fractionation schemes (2 Gy, 3 Gy, and 5 Gy fraction dose) and the dose of one CBCT scan was additionally added to the treatment dose per fraction applied with the linear accelerator. The resulting absorbed doses per fraction of the two machines were compared. RESULTS: In the target region, all measured treatment plans presented the same magnitude of dose, while the CBCT dose was a factor of 100 smaller. Close to the planned target volume (PTV), the dose from the 60 Co machine was a factor of two higher compared with the 3DCRT + CBCT dose. Up to 45 cm from the PTV, the treatment applied with the 60 Co-sources showed an increased out-of-field dose compared to the linear accelerator + CBCT IGRT treatments. Further away from the PTV in the region where leakage from the gantry head is dominating, the out-of-field dose of the Cobalt machine was smaller compared to the linear accelerator + CBCT. CONCLUSION: The peripheral dose of the 60 Co machine combined with an MRI is larger up to 45 cm from the PTV and further away, it is lower than the dose from a linear accelerator + CBCT treatment. The presented fractionation schemes had a marginal impact on the results.

Neutrons in active proton therapy: Parameterization of dose and dose equivalent.

PURPOSE: One of the essential elements of an epidemiological study to decide if proton therapy may be associated with increased or decreased subsequent malignancies compared to photon therapy is an ability to estimate all doses to non-target tissues, including neutron dose. This work therefore aims to predict for patients using proton pencil beam scanning the spatially localized neutron doses and dose equivalents. METHODS: The proton pencil beam of Gantry 1 at the Paul Scherrer Institute (PSI) was Monte Carlo simulated using GEANT. Based on the simulated neutron dose and neutron spectra an analytical mechanistic dose model was developed. The pencil beam algorithm used for treatment planning at PSI has been extended using the developed model in order to calculate the neutron component of the delivered dose distribution for each treated patient. The neutron dose was estimated for two patient example cases. RESULTS: The analytical neutron dose model represents the three-dimensional Monte Carlo simulated dose distribution up to 85cm from the proton pencil beam with a satisfying precision. The root mean square error between Monte Carlo simulation and model is largest for 138MeV protons and is 19% and 20% for dose and dose equivalent, respectively. The model was successfully integrated into the PSI treatment planning system. In average the neutron dose is increased by 10% or 65% when using 160MeV or 177MeV instead of 138MeV. For the neutron dose equivalent the increase is 8% and 57%. CONCLUSIONS: The presented neutron dose calculations allow for estimates of dose that can be used in subsequent epidemiological studies or, should the need arise, to estimate the neutron dose at any point where a subsequent secondary tumour may occur. It was found that the neutron dose to the patient is heavily increased with proton energy.

Neutrons in proton pencil beam scanning: parameterization of energy, quality factors and RBE.

The biological effectiveness of neutrons produced during proton therapy in inducing cancer is unknown, but potentially large. In particular, since neutron biological effectiveness is energy dependent, it is necessary to estimate, besides the dose, also the energy spectra, in order to obtain quantities which could be a measure of the biological effectiveness and test current models and new approaches against epidemiological studies on cancer induction after proton therapy. For patients treated with proton pencil beam scanning, this work aims to predict the spatially localized neutron energies, the effective quality factor, the weighting factor according to ICRP, and two RBE values, the first obtained from the saturation corrected dose mean lineal energy and the second from DSB cluster induction. A proton pencil beam was Monte Carlo simulated using GEANT. Based on the simulated neutron spectra for three different proton beam energies a parameterization of energy, quality factors and RBE was calculated. The pencil beam algorithm used for treatment planning at PSI has been extended using the developed parameterizations in order to calculate the spatially localized neutron energy, quality factors and RBE for each treated patient. The parameterization represents the simple quantification of neutron energy in two energy bins and the quality factors and RBE with a satisfying precision up to 85 cm away from the proton pencil beam when compared to the results based on 3D Monte Carlo simulations. The root mean square error of the energy estimate between Monte Carlo simulation based results and the parameterization is 3.9%. For the quality factors and RBE estimates it is smaller than 0.9%. The model was successfully integrated into the PSI treatment planning system. It was found that the parameterizations for neutron energy, quality factors and RBE were independent of proton energy in the investigated energy range of interest for proton therapy. The pencil beam algorithm has been extended using the developed parameterizations in order to calculate the neutron energy, quality factor and RBE.

A general model for stray dose calculation of static and intensity-modulated photon radiation.

PURPOSE: There is an increasing number of cancer survivors who are at risk of developing late effects caused by ionizing radiation such as induction of second tumors. Hence, the determination of out-of-field dose for a particular treatment plan in the patient's anatomy is of great importance. The purpose of this study was to analytically model the stray dose according to its three major components. METHODS: For patient scatter, a mechanistic model was developed. For collimator scatter and head leakage, an empirical approach was used. The models utilize a nominal beam energy of 6 MeV to describe two linear accelerator types of a single vendor. The parameters of the models were adjusted using ionization chamber measurements registering total absorbed dose in simple geometries. Whole-body dose measurements using thermoluminescent dosimeters in an anthropomorphic phantom for static and intensity-modulated treatment plans were compared to the 3D out-of-field dose distributions calculated by a combined model. RESULTS: The absolute mean difference between the whole-body predicted and the measured out-of-field dose of four different plans was 11% with a maximum difference below 44%. Computation time of 36 000 dose points for one field was around 30 s. By combining the model-calculated stray dose with the treatment planning system dose, the whole-body dose distribution can be viewed in the treatment planning system. CONCLUSIONS: The results suggest that the model is accurate, fast and can be used for a wide range of treatment modalities to calculate the whole-body dose distribution for clinical analysis. For similar energy spectra, the mechanistic patient scatter model can be used independently of treatment machine or beam orientation.

Accuracy of out-of-field dose calculation of tomotherapy and cyberknife treatment planning systems: a dosimetric study.

PURPOSE: Late toxicities such as second cancer induction become more important as treatment outcome improves. Often the dose distribution calculated with a commercial treatment planning system (TPS) is used to estimate radiation carcinogenesis for the radiotherapy patient. However, for locations beyond the treatment field borders, the accuracy is not well known. The aim of this study was to perform detailed out-of-field-measurements for a typical radiotherapy treatment plan administered with a Cyberknife and a Tomotherapy machine and to compare the measurements to the predictions of the TPS. MATERIALS AND METHODS: Individually calibrated thermoluminescent dosimeters were used to measure absorbed dose in an anthropomorphic phantom at 184 locations. The measured dose distributions from 6 MV intensity-modulated treatment beams for CyberKnife and TomoTherapy machines were compared to the dose calculations from the TPS. RESULTS: The TPS are underestimating the dose far away from the target volume. Quantitatively the Cyberknife underestimates the dose at 40 cm from the PTV border by a factor of 60, the Tomotherapy TPS by a factor of two. If a 50% dose uncertainty is accepted, the Cyberknife TPS can predict doses down to approximately 10 mGy/treatment Gy, the Tomotherapy-TPS down to 0.75 mGy/treatment Gy. The Cyberknife TPS can then be used up to 10 cm from the PTV border the Tomotherapy up to 35 cm. CONCLUSIONS: We determined that the Cyberknife and Tomotherapy TPS underestimate substantially the doses far away from the treated volume. It is recommended not to use out-of-field doses from the Cyberknife TPS for applications like modeling of second cancer induction. The Tomotherapy TPS can be used up to 35 cm from the PTV border (for a 390 cm(3) large PTV).

Measurement of skin and target dose in post-mastectomy radiotherapy using 4 and 6 MV photon beams.

BACKGROUND: For patients with high risk breast cancer and mastectomy, radiotherapy is the treatment of choice to improve survival and local control. Target dose is mainly limited due to skin reactions. The feasibility of using 4 MV beams for chest wall treatment was studied and compared to standard 6 MV bolus radiotherapy. METHODS: Post-mastectomy IMRT was planned on an Alderson-phantom using 4 and 6 MV photon beams without/with a 0.5 cm thick bolus. Dose was measured using TLDs placed at 8 locations in 1 and 3 mm depth to represent skin and superficial target dose, respectively. RESULTS: 4 MV and 6 MV beams with bolus perform equally regarding target coverage. The minimum and mean superficial target dose for the 6 MV and 4 MV were 93.0% and 94.7%, and 93.1% and 94.4%, respectively. Regarding skin dose the 4 MV photon beam was advantageous. The minimum and mean skin dose for the 6 MV and 4 MV was 76.7% and 81.6%, and 69.4% and 72.9%, respectively. The TPS was able to predict dose in the build-up region with a precision of around 5%. CONCLUSIONS: The use of 4 MV photon beams are a good alternative for treating the thoracic wall without the need to place a bolus on the patient. The main limitation of 4 MV beams is the limited dose rate.

Systematic measurements of whole-body imaging dose distributions in image-guided radiation therapy.

PURPOSE: The full benefit of the increased precision of contemporary treatment techniques can only be exploited if the accuracy of the patient positioning is guaranteed. Therefore, more and more imaging modalities are used in the process of the patient setup in clinical routine of radiation therapy. The improved accuracy in patient positioning, however, results in additional dose contributions to the integral patient dose. To quantify this, absorbed dose measurements from typical imaging procedures involved in an image-guided radiation therapy treatment were measured in an anthropomorphic phantom for a complete course of treatment. The experimental setup, including the measurement positions in the phantom, was exactly the same as in a preceding study of radiotherapy stray dose measurements. This allows a direct combination of imaging dose distributions with the therapy dose distribution. METHODS: Individually calibrated thermoluminescent dosimeters were used to measure absorbed dose in an anthropomorphic phantom at 184 locations. The dose distributions from imaging devices used with treatment machines from the manufacturers Accuray, Elekta, Siemens, and Varian and from computed tomography scanners from GE Healthcare were determined and the resulting effective dose was calculated. The list of investigated imaging techniques consisted of cone beam computed tomography (kilo- and megavoltage), megavoltage fan beam computed tomography, kilo- and megavoltage planar imaging, planning computed tomography with and without gating methods and planar scout views. RESULTS: A conventional 3D planning CT resulted in an effective dose additional to the treatment stray dose of less than 1 mSv outside of the treated volume, whereas a 4D planning CT resulted in a 10 times larger dose. For a daily setup of the patient with two planar kilovoltage images or with a fan beam CT at the TomoTherapy unit, an additional effective dose outside of the treated volume of less than 0.4 mSv and 1.4 mSv was measured, respectively. Using kilovoltage or megavoltage radiation to obtain cone beam computed tomography scans led to an additional dose of 8-46 mSv. For treatment verification images performed once per week using double exposure technique, an additional effective dose of up to 18 mSv was measured. CONCLUSIONS: Daily setup imaging using kilovoltage planar images or TomoTherapy megavoltage fan beam CT imaging can be used as a standard procedure in clinical routine. Daily kilovoltage and megavoltage cone beam computed tomography setup imaging should be applied on an individual or indication based protocol. Depending on the imaging scheme applied, image-guided radiation therapy can be administered without increasing the dose outside of the treated volume compared to therapies without image guidance.

Systematic measurements of whole-body dose distributions for various treatment machines and delivery techniques in radiation therapy.

PURPOSE: Contemporary radiotherapy treatment techniques, such as intensity-modulated radiation therapy and volumetric modulated arc therapy, could increase the radiation-induced malignancies because of the increased beam-on time, i.e., number of monitor units needed to deliver the same dose to the target and the larger volume irradiated with low doses. In this study, whole-body dose distributions from typical radiotherapy patient plans using different treatment techniques and therapy machines were measured using the same measurement setup and irradiation intention. METHODS: Individually calibrated thermoluminescent dosimeters were used to measure absorbed dose in an anthropomorphic phantom at 184 locations. The dose distributions from 6 MV beams were compared in terms of treatment technique (3D-conformal, intensity-modulated radiation therapy, volumetric modulated arc therapy, helical TomoTherapy, stereotactic radiotherapy, hard wedges, and flattening filter-free radiotherapy) and therapy machine (Elekta, Siemens and Varian linear accelerators, Accuray CyberKnife and TomoTherapy). RESULTS: Close to the target, the doses from intensity-modulated treatments (including flattening filter-free) were below the dose from a static treatment plan, whereas the CyberKnife showed a larger dose by a factor of two. Far away from the treatment field, the dose from intensity-modulated treatments showed an increase in dose from stray radiation of about 50% compared to the 3D-conformal treatment. For the flattening filter-free photon beams, the dose from stray radiation far away from the target was slightly lower than the dose from a static treatment. The CyberKnife irradiation and the treatment using hard wedges increased the dose from stray radiation by nearly a factor of three compared to the 3D-conformal treatment. CONCLUSIONS: This study showed that the dose outside of the treated volume is influenced by several sources. Therefore, when comparing different treatment techniques, the dose ratios vary with distance to the isocenter. The effective dose outside the treated volume of intensity-modulated treatments with or without flattening filter was 10%-30% larger when compared to 3D-conformal radiotherapy. This dose increase is much lower than the monitor unit scaled effective dose from a static treatment.

Monitor units are not predictive of neutron dose for high-energy IMRT.

BACKGROUND: Due to the substantial increase in beam-on time of high energy intensity-modulated radiotherapy (>10 MV) techniques to deliver the same target dose compared to conventional treatment techniques, an increased dose of scatter radiation, including neutrons, is delivered to the patient. As a consequence, an increase in second malignancies may be expected in the future with the application of intensity-modulated radiotherapy. It is commonly assumed that the neutron dose equivalent scales with the number of monitor units. METHODS: Measurements of neutron dose equivalent were performed for an open and an intensity-modulated field at four positions: inside and outside of the treatment field at 0.2 cm and 15 cm depth, respectively. RESULTS: It was shown that the neutron dose equivalent, which a patient receives during an intensity-modulated radiotherapy treatment, does not scale with the ratio of applied monitor units relative to an open field irradiation. Outside the treatment volume at larger depth 35% less neutron dose equivalent is delivered than expected. CONCLUSIONS: The predicted increase of second cancer induction rates from intensity-modulated treatment techniques can be overestimated when the neutron dose is simply scaled with monitor units.

Comparative simulations of neutron dose in soft tissue and phantom materials for proton and carbon ion therapy with actively scanned beams.

PURPOSE: In the clinical environment phantom materials are usually used to simulate the patient for neutron dosimetric measurements. It is not clear that the results of such phantom measurements represent the actual neutron dose in the patient. The aim of this study was to compare the difference in secondary neutron equivalent dose for different phantom materials to that in human tissue, for both proton and carbon ion radiation therapy. METHODS: In order to compare the neutron equivalent dose induced by primary particles in different materials, Monte Carlo simulations were performed using the FLUKA Monte Carlo package. The scored dosimetric quantities were absorbed dose and neutron ambient dose equivalent for monoenergetic proton and carbon ion beams of clinically relevant energies. It was shown that neutron equivalent dose, for which no scoring routine exists in the current FLUKA release, can be approximated by neutron ambient dose equivalent within 4% for the investigated energies of proton and carbon ion beams. RESULTS: The Monte Carlo simulations performed in this work showed differences in neutron ambient dose equivalent in radiation therapy phantom materials compared to ICRP soft tissue for primary proton and carbon ion beams. For Alderson soft tissue the maximum deviation was 11% for protons and 8% for carbon ions. For water the maximum deviation was 10% for protons and 9% for carbon ions. In the case of RW3 solid water, the maximum deviation compared to ICRP soft tissue was as large as 28% and 21% for protons and carbon ions, respectively. CONCLUSIONS: Alderson soft tissue and water are suitable phantom materials for neutron dosimetry for the accuracy which is achievable. When using solid water phantoms, the chemical and therefore nuclear composition of the phantom material has to be accounted for.

The value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography for staging of primary extranodal head and neck lymphomas.

OBJECTIVES/HYPOTHESIS: Using a retrospective approach, the aim of this study was to confirm the previously described value of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) in patients with primary extranodal lymphoma of the head and neck region. Additionally, the clinical significance of the semiquantitative analysis of the standardized uptake value (SUV), its predictive role in the follow-up setting, and its value in detection of synchronous primaries were studied. STUDY DESIGN: Retrospective chart review. METHODS: Twenty-six patients with a primary extranodal head and neck lymphoma (22 diffuse large B-cell lymphoma, one Hodgkin's lymphoma, three malignant T-cell lymphomas) were included. We retrospectively evaluated the clinical outcomes according to the maximum standardized uptake values of the primary lesion (SUV(max)) and whether a positron emission tomography/computed tomography (PET/CT) was performed or not in the follow-up studies. The median SUV(max) was chosen as the cutoff value. The patients were then grouped as those with either low or high SUV(max), respective to the cutoff value. Event-free survival and cumulative survival were endpoints of interest. RESULTS: Nineteen patients (73%) were above the age of 60 years; the median age was 70 years (range, 28-87 years). Most primary sites were in the Waldeyer's ring (15 patients, 60%), whereas in four patients (27%) only the palatine tonsil was affected. The SUV(max) ranged from 5.8 to 33.9. In one patient, relevant fluorodeoxyglucose (FDG) uptake within the intestine revealed a cecal adenocarcinoma as a secondary primary. Twenty of the 25 clinically followed patients (80%) achieved complete remission after treatment. Patients with high SUV(max) showed favorable survival (log-rank test, P = .044). A tendency for longer survival within the group with follow-up PET/CT studies could be noted but with no significant statistical difference (P = .349). CONCLUSIONS: (18)F-FDG-PET/CT imaging is a potent primary staging tool. It also has application as an instrument for evaluation of follow-up and response to therapy in patients suffering from primary extranodal lymphoma and for detection of secondary malignancies. Furthermore, (18)F-FDG uptake by the primary lesion may be related to better survival.