3D printing for dosimetric optimization and quality assurance in small animal irradiations using megavoltage X-rays

PurposeNew therapeutic options in radiotherapy (RT) are often explored in preclinical in-vivo studies using small animals. We report here on the feasibility of modern megavoltage (MV) linear accelerator (LINAC)-based RT for small animals using easy-to-use consumer 3D printing technology for dosimetric optimization and quality assurance (QA).MethodsIn this study we aimed to deliver 5 × 2 Gy to the half-brain of a rat using a 4 MV direct hemi-field X-ray beam. To avoid the beam's build-up in the target and optimize dosimetry, a 1 cm thick, customized, 3D-printed bolus was used. A 1:1 scale copy of the rat was 3D printed based on the CT dataset as an end-to-end QA tool. The plan robustness to HU changes was verified. Thermoluminescent dosimeters (TLDs), for both MV irradiations and for kV imaging doses, and a gafchromic film were placed within the phantom for dose delivery verifications. The phantom was designed using a standard treatment planning software, and was irradiated at the LINAC with the target aligned using kV on-board imaging.ResultsThe plan was robust (dose difference < 1% for HU modification from 0 to 250). Film dosimetry showed a good concordance between planned and measured dose, with the steep dose gradient at the edge of the hemi-field properly aligned to spare the contralateral half-brain. In the treated region, the mean TLDs percentage dose differences (±2 SD) were 1.3% (±3.8%) and 0.9% (±1.7%) beneath the bolus. The mean (±2 SD) out-of-field dose measurements was 0.05 Gy (±0.02 Gy) for an expected dose of 0.04 Gy. Imaging doses (2 mGy) still spared the contralateral-brain.ConclusionsUse of consumer 3D-printers enables dosimetry optimization and QA assessment for small animals MV RT in preclinical studies using standard LINACS.     

Radiation dose to the low axilla in patients treated for early-stage breast cancer by locoregional intensity-modulated radiotherapy (IMRT)

PurposeTo determine the dose received by the low axilla during locoregional radiotherapy (RT) for early-stage breast cancer and to assess the impact of the treatment technique (three-dimensional conformal radiotherapy (3D-CRT) or rotational IMRT (VMAT) or helical tomotherapy (HT).Materials and methodsThe dosimetric study was performed on patients receiving normofractionated (NFRT - 50 Gy in 25 fractions) or hypofractionated (HFRT - 40 Gy in 15 fractions) locoregional radiotherapy (breast or chest wall and internal mammary, supraclavicular and infraclavicular nodes ± axillary nodes) by 3D-CRT or VMAT or HT at the Institut Curie Paris. Patients treated by breast-conserving surgery received a boost dose of 16 Gy and 10 Gy to the tumour bed, respectively.ResultsSixty-eight patients treated by RT from February 2017 to January 2019 were studied. The mean dose received by the low axilla when it was not part of the target volume was 30.8 Gy, 41.0 Gy and 44.4 Gy by 3D-CRT, VMAT and HT, respectively for NFRT and 24.2 Gy, 33.0 Gy and 34.9 Gy, respectively, for HFRT. With NFRT, 4.1% of the axilla received 95% (V95) of the prescribed dose by 3D-CRT compared to 24.5% and 33.6% by VMAT and HT, respectively; with HFRT, V95 was 3.9%, 19.5% and 24.1%, respectively.ConclusionThe axilla receives a non-negligible dose during locoregional radiotherapy; this dose is greater when VMAT or HT are used. Prospective studies must be conducted to assess the impact of this axillary dose in terms of morbidity, which currently remains unknown.     

Can we predict the cardiac benefit of deep inspiration breath hold for left breast and regional nodal irradiation?

PurposeDeep inspiration breath hold (DIBH) is used to decrease the dose of radiotherapy delivered to the heart. There is a need to define criteria to select patients with the potential to derive a real clinical benefit from DIBH treatment. Our study's main goal was to investigate whether two CT-scan cardiac anatomical parameters, cardiac contact distance in the parasagittal plane (CCDps) and lateral heart-to-chest distance (HCD), were predictive of unmet dosimetric cardiac constraints for left breast and regional nodal irradiation (RNI).Materials and methodsThis retrospective single-institution dosimetric study included 62 planning CT scans of women with left-sided breast cancer (BC) from 2016 to 2021. Two independent radiation oncologists measured HCD and CCDps twice to assess inter- and intra-observer reproducibility. Dosimetric constraints to be respected were defined, and dosimetric parameters of interest were collected for each patient.ResultsMean heart dose was 7.9 Gy. Inter-rater reproducibility between the two readers was considered excellent. The mean heart dose constraint < 8 Gy was not achieved in 25 patients (40%) and was achieved in 37 patients (60%). There was a significant correlation between mean heart dose and HCD (r_s = –0.25, P = 0.050) and between mean heart dose and CCDps (r_s = 0.25, P = 0.047). The correlation between HCD and CCDps and unmet cardiac dosimetric constraints was not statistically significant.ConclusionOur dosimetric analysis did not find that the cardiac anatomical parameters HCD and CCDps were predictive of unmet dosimetric cardiac constraints, nor that they were good predictors for cardiac exposure in left-sided BC radiotherapy comprising RNI.     

Tolerance and efficacy of dose escalation using IMRT combined with chemotherapy for unresectable esophageal carcinoma: Long-term results of 51 patients

PurposeThe optimal dose in esophageal cancer patients treated with definitive chemoradiation (CRT) remains debated. We herein report on the dosimetric results, treatment-related toxicities and long-term outcomes of escalated dose up to 60 Gy delivered with intensity-modulated radiotherapy (IMRT).Materials and methodsAll consecutive patients that received a definitive CRT > 50 Gy for an unresectable esophageal carcinoma between 2010 and 2015 were retrospectively evaluated for this study. Methodology included data base search, delayed toxicity grading, statistical testing including frequency analysis and survival analysis.ResultsA total of 51 patients were irradiated for a squamous cell carcinoma (86.3%) or an adenocarcinoma (13.7%). The median age at diagnosis was 62 years. Seven patients were simultaneously irradiated for another synchronous primary tumor. Forty-six patients (90.2%) received concurrent platin-based chemotherapy. The median prescribed doses were 60 Gy (54–66) and 48 Gy (44.8–56) delivered in 30 (27–35) fractions to the high and the low risks PTV respectively. The mean dose delivered to the lungs was 11.4 Gy (IC 95%: 4.8–19.8), the median volumes receiving up to 20 Gy (V20) and 30 Gy (V30) were 13.5% (3.0–46.0) and 4.6% (0.7–19.8) respectively. The mean dose delivered to the heart was 13.9 Gy (IC 95%:0.3–31.3) with a median V40 of 3.3% (0.0–25.0). One treatment-related death occurred within days after RT completion (neutropenic aplasia). After a median follow-up of 2.7 years (95% CI: 1.9–4.3), the 2-year overall survival, disease free survival and loco-regional control rates were 53.6%, 42.0% and 72.8% respectively. Delayed treatment related-toxicities ≤ grade 3 occurred among 25 patients (62.5%) mostly esophageal stricture (79.2%).ConclusionWe demonstrated in this study that dose escalation using IMRT in combination with platin-based chemotherapy as a definitive treatment for esophageal carcinoma is safe and results in higher loco-regional and control survival when compared to previously reported data.     

Dose distribution of the brain tissue associated with cognitive functions in high-grade glioma patients

PurposeThe purpose of this prospective dosimetric study was to assess the dose distribution regarding the brain areas implied in cognitive functions using two approaches: volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT).Patients and methodsThirty-seven patients were treated using a dual-arc VMAT approach for supratentorial glioblastoma between 2016 and 2018. The total dose of 60 Gy in 30 daily fractions was administered to the planning target volume (PTV). The brain structures that play an important role in cognitive physiology, such as the hippocampi, corpus callosum, cerebellum, subventricular zones (SVZ), were delineated. For each patient, a new treatment plan in HT was determined by a second medical physicist in a blindly fashion according to the same dose constraints and priorities. Statistical analyses were performed using the Wilcoxon-signed rank test.ResultsConformity indexes remained similar with both techniques. The mean values were 0.96 (0.19–1.00) for VMAT and 0.98 (range, 0.84–1.00) for HT, respectively (P = 0.73). Significant D_50% reductions were observed with VMAT compared to HT: 14.6 Gy (3.8–28.0) versus 17.4 Gy (12.1–25.0) for the normal brain (P = 0.014); 32.5 Gy (10.3–60.0) versus 35.6 Gy (17.1–58.0) for the corpus callosum (P = 0.038); 8.1 Gy (0.4–34.0) versus 12.8 Gy (0.8–27.0) for the cerebellum (P < 0.001), respectively.ConclusionThe VMAT approach seemed to improve the sparing of the key brain areas implied in cognitive functions without jeopardizing PTV coverage.     

Dosimetric analysis of urethral strictures following HDR 192Ir brachytherapy as monotherapy for intermediate- and high-risk prostate cancer

Background and purposeTo evaluate dosimetric parameters related to urethral strictures following high dose-rate brachytherapy (HDRBT) alone for prostate cancer.Material and methodsTen strictures were identified in 213 patients treated with HDRBT alone receiving 34 Gy in four fractions, 36 Gy in four fractions, 31.5 Gy in 3 fractions or 26 Gy in 2 fractions. A matched-pair analysis used 2 controls for each case matched for dose fractionation schedule, pre-treatment IPSS score, number of needles used and clinical target volume. The urethra was divided into membranous urethra and inferior, mid and superior thirds of the prostatic urethra.ResultsStricture rates were 3% in the 34 Gy group, 4% in the 36 Gy group, 6% in the 31.5 Gy group and 4% in the 26 Gy group. The median time to stricture formation was 26 months (range 8–40). The dosimetric parameters investigated were not statistically different between cases and controls. No correlation was seen between stricture rate and fractionation schedule.ConclusionsUrethral stricture is an infrequent complication of prostate HDRBT when used to deliver high doses as sole treatment, with an overall incidence in this cohort of 10/213 (4.7%). In a matched pair analysis no association with dose schedule or urethral dosimetry was identified, but the small number of events limits definitive conclusions.     

Total body irradiation: Significant dose sparing of lung tissue achievable by helical tomotherapy

PurposeTotal body irradiation (TBI) is an important procedure in the conditioning for bone marrow and hematopoietic stem cell transplantation. Doses up to 12 Gy are delivered in hyperfractionated regimes. TBI performed with helical Tomotherapy® (Accuray, Madison, Wisconsin, USA) is an alternative to conventional techniques to deliver dose in extended target volumes with the possibility of simultaneous dose sparing to organs at risk. In this study we focused on maximum dose reduction to the lungs in TBI using helical Tomotherapy®.Material and methodsForty treatment plans of patients who received TBI were calculated with TomoH® (Accuray, Madison, Wisconsin, USA, Version 2.0.4) with a dose of 12 Gy delivered in six equal fractions (2 × 2 Gy/day). Planning iterations necessary to accomplish ICRU 83 report should be less than 250. Treatment time should be practicable in daily routine (<60 min.). Besides the usual contouring of organs at risk special contouring was required for optimization processes which focused on maximum dose sparing in the central lung tissue. Dose constraints (D2, D98, D99) were predefined for target volumes (i.e. PTV TBI D99: 90% of prescribed dose). Homogeneity index <0.15 was defined for acceptability of the treatment plan.ResultsFor all patients acceptable treatment plan fulfilling the predefined constraints were achievable. An average time of 46 min is required for treatment. Thirty-four of forty patients fulfilled D2 in the PTV TBI. Four patients failed D2 due to a high BMI >28 (maximum dose 13.76 Gy = 114.7%). The D98 in the PTV TBI was not reached by 2/40 patients due to BMI > 31 (minimum dose 11.31 Gy = dose coverage of 94.2%). Also these two patients failed the homogeneity index <0.15. The mean lung dose over all patients of the right lung was 7.18 Gy (range 6.4–9.5 Gy). The left lung showed a median (D50) dose of 7.9 Gy (range 6.7–9.3 Gy). Central lung dose showed a mean dose (D50) of 5.16 Gy (range 4.02–7.29 Gy). The D80 of the central lung showed an average dose of 3.87 Gy.ConclusionsTotal body irradiation using helical Tomotherapy® can be delivered with maximum lung tissue sparing (<6 Gy) but without compromise in adjacent PTV TBI structures (i.e. ribs, heart). High conformity and homogeneity in extended radiation volumes can be reached with this technique in an acceptable planning and treatment time. Limitations may occurred in patients with high body mass index.     

Dosimetric challenges of small animal irradiation with a commercial X-ray unit

IntroductionA commercial X-ray unit was recently installed at the Medical University Vienna for partial and whole body irradiation of small experimental animals. For 200 kV X-rays the dose deviations with respect to the reference dose measured in the geometrical center of the potential available field size was investigated for various experimental setup plates used for mouse irradiations. Furthermore, the HVL was measured in mm Al and mm Cu at 200 kV for two types of filtration.Material and MethodsThree different setup constructions for small animal irradiation were dosimetrically characterized, covering field sizes from 9 × 20 mm² to 210 × 200 mm². Different types of detectors were investigated. Additionally LiF:MG,Ti TLD chips were used for mouse in-vivo dosimetry.ResultsThe use of an additional 0.5 mm Cu filter reduced the deviation of the dose between each irradiation position on the setup plates. Multiple animals were irradiated at the same time using an individual setup plate for each experimental purpose. The dose deviations of each irradiation position to the center was measured to be ±4% or better. The depth dose curve measured in a solid water phantom was more pronounced for smaller field sizes. The comparison between estimated dose and measured dose in a PMMA phantom regarding the dose decline yielded in a difference of 3.9% at 20 mm depth. In-vivo measurements in a mouse snouts irradiation model confirmed the reference dosimetry, accomplished in PMMA phantoms, in terms of administered dose and deviation within different points of measurement.Discussion and ConclusionThe outlined experiments dealt with a wide variety of dosimetric challenges during the installation of a new X-ray unit in the laboratory. The depth dose profiles measured for different field sizes were in good agreement with literature data. Different field sizes and spatial arrangement of the animals (depending on each purpose) provide additional challenges for the dosimetric measurements. Thorough dosimetric commissioning has to be performed before a new experimental setup is approved for biological experiments.     

Lumbosacral spine and marrow cavity modeling of acute hematologic toxicity in patients treated with intensity modulated radiation therapy for squamous cell carcinoma of the anal canal

PurposeTo identify various dosimetric parameters of bone marrow cavity that correlate with acute hematologic toxicity (HT) in patients with anal squamous cell carcinoma treated with definitive chemoradiation therapy (CRT).Methods and materialsWe analyzed 32 patients receiving CRT. The whole pelvic bone marrow (PBM) and the lumbosacral spine (LSS) subregion were contoured for each patient. Marrow cavities were contoured using the Hounsfield units (HUs) of 100, 150, 200, and 250 as maximum density threshold levels. The volume of each region receiving at least 5, 10, 15, 20, 30, and 40 Gy was calculated. The endpoint was grade ≥ 3 HT (HT3 +). Normal-tissue complication probability (NTCP) was evaluated with the Lyman-Kutcher-Burman (LKB) model. Maximal likelihood estimate was used to compare the parameter set. Logistic regression was used to test associations between HT and both dosimetric and clinical parameters.ResultsTen patients (31%) experienced HT3 +. While dose to both LSS and PBM significantly predicted for HT3 +, LSS was superior to PBM by logistic regression and LKB modeling. Constrained optimization of the LKB model for HT3 + yielded the parameters m = 0.21, n = 1, and TD₅₀ = 32 Gy for LSS. The NTCP fits were better with the whole bone than with marrow cavity using any HU threshold. Mean LSS doses of 21 Gy and 23.5 Gy result in a 5% and 10% risk of HT3 +, respectively. Mean dose and low-dose radiation parameters (V5, V10, V15, V20) of whole bone or bone cavities of LSS were correlated most significantly with HT3 +.ConclusionsFor predicting the risk of HT3 +, whole-bone contours were superior to marrow cavity and LSS was superior to PBM by LKB modeling. The results confirm PBM and LSS as parallel organs when predicting hematologic toxicity. Recommended dose constraints to the LSS are V10 ≤80%. An LSS mean dose of 23.5 Gy is associated with a 10% risk of HT.     

Systematic dosimetric evaluation of risk of osteoradionecrosis (DERO): First results of dose reporting for preventing teeth osteoradionecrosis after head and neck irradiation

PurposeOsteoRadioNecrosis (ORN) is a late complication of radiation for head and neck cancer. Predicting ORN is a major challenge. We developed DERO (Dosimetric Evaluation of Risk of ORN), a semi-automatic tool which reports doses delivered to tooth-bearing sectors, to guide post-therapeutic dental care. We present the method and the first results of a 125-patient prospective cohort.Material and methodsDosimetric data of patients treated with IMRT for head and neck cancer were prospectively segmented to the DERO algorithm. Four arches corresponding to 8-tooth sectors were semi-automatically generated. Thirty-two cylindrical Regions Of Interest (ROI) corresponding to each tooth and surrounding periodontium were created by linear interpolation. Mean doses (Dmean) of ROI were extracted and included in a database, along with data about primary tumor site, laterality and dose values from organs at risk. Dmean to tooth sectors were computed for molar sectors, (teeth X5 to X8) and anterior sectors (teeth X1 to X4). An individual dose map was generated and delivered to patients and dentists.ResultsDosimetric data from 125 patients treated with Tomotherapy® were prospectively collected and analyzed: 9 parotid tumors (PA), 41 Sub-Hyoid tumors (larynx, hypopharynx) (SH), 43 Oropharynx tumors (OR), 32 Oral Cavity tumors (OC). Irradiation was unilateral for 100% of PA tumors (9), 12% of OR tumors (5) and 47% of OC tumors (15). For unilateral cervical irradiation, Dmean in ipsilateral molar sectors was 54 Gy for OC tumors, 45 Gy for OR tumors, 20 Gy for PA tumors. For Oral Cavity bilateral irradiation, Dmean was high in all tooth sectors, 49 to 55 Gy. For SH tumors, Dmean in molar sectors was 27 Gy. A dose gradient of 10 to 20 Gy was observed between molar and anterior sectors whether radiation was uni or bilateral.ConclusionMandibular molar sectors of Oropharynx and Oral Cavity tumors were exposed to high Dmean of 40 to 50 Gy. On the other hand, tooth sectors received lower doses for SH radiation. The DERO tool guide post-radiation dental care with a personalized dosimetric cartography to patient. With data update and patient follow-up, we will be able to determine ORN risk after head and neck radiation.     

Comparison between the ICRU rectal point and modern volumetric parameters in brachytherapy for locally advanced cervical cancer

PurposeThe implementation of image-guided brachytherapy in cervical cancer raises the problem of adapting the experience acquired with 2D brachytherapy to this technique. The GEC-ESTRO (Groupe européen de curiethérapie – European Society for Radiotherapy and Oncology) has recommended reporting the dose delivered to the rectum in the maximally exposed 2 cm³ volume, but so far, the recommended dose constraints still rely on 2D data. The aim of this study was to evaluate the relationship between the doses evaluated at the ICRU rectal point and modern dosimetric parameters.Material and methodsFor each patient, dosimetric parameters were generated prospectively at the time of dosimetry and were reported. For analysis, they were converted in 2 Gy equivalent doses using an α/β ratio of 3 with a half-time of repair of 1.5 hours.ResultsThe dosimetric data from 229 consecutive patients treated for locally advanced cervical cancer was analyzed. The mean dose calculated at ICRU point (DICRU) was 55.75 Gy ± 4.15, while it was 59.27 Gy ± 6.16 in the maximally exposed 2 cm³ of the rectum (P = 0.0003). The D2 cm³ was higher than the DICRU in 78% of the cases. The mean difference between D2 cm³ and DICRU was 3.53 Gy ± 4.91. This difference represented 5.41% ± 7.40 of the total dose delivered to the rectum (EBRT and BT), and 15.49% ± 24.30 of the dose delivered when considering brachytherapy alone. The two parameters were significantly correlated (P = 0.000001), and related by the equation: D2 cm³ = 0.902 × DICRU + 0.984. The r² coefficient was 0.369.ConclusionIn this large cohort of patients, the DICRU significantly underestimates the D2 cm³. This difference probably results from the optimization process itself, which consists in increasing dwell times above the ICRU point in the cervix. Considering these findings, caution must be taken while implementing image-guided brachytherapy and dose escalation.     

Brain dose-sparing radiotherapy techniques for localized intracranial germinoma: Case report and literature review of modern irradiation

We examined the effects of intensity-modulated radiation therapy with dose-sparing and avoidance technique on a pediatric patient with localized intracranial germinoma. We also reviewed the literature regarding modern irradiation techniques in relation to late neurocognitive sequelae. A patient with a localized intracranial germinoma in the third ventricle anterior to the pineal gland received a dose-sparing intensity-modulated radiation therapy. The planning was compared to the radiation oncologist's guide of organs at risk and dose constraints for dosimetric analyses. The patient received radiation therapy alone. The total dose was 54 Gy delivered in 2.0 Gy fractions to the primary tumour and 37 Gy in 1.4 Gy fractions to whole ventricles using a dose-sculpting plan. Dosimetry analyses showed that dose-sparing intensity-modulated radiation therapy delivered reduced doses to the whole brain, temporal lobes, hippocampi, cochleae, and optic nerves. With a follow-up of 22 months, failure-free survival was 100% for the patient and no adverse events during radiation treatment process. Intensity-modulated radiation therapy with dose sparing and avoidance technique can spare the limbic circuit, central nervous system, and hippocampus for pineal germ cell tumours. This technique reduces the integral dose delivered to the uninvolved normal brain tissues and may reduce late neurocognitive sequelae caused by cranial radiotherapy.     

Results of an independent dosimetry audit for scanned proton beam therapy facilities

PurposeAn independent dosimetry audit based on end-to-end testing of the entire chain of radiation therapy delivery is highly recommended to ensure consistent treatments among proton therapy centers. This study presents an auditing methodology developed by the MedAustron Ion Beam Therapy Center (Austria) in collaboration with the National Physical Laboratory (UK) and audit results for five scanned proton beam therapy facilities in Europe.MethodsThe audit procedure used a homogeneous and an anthropomorphic head phantom. The phantoms were loaded either with an ionization chamber or with alanine pellets and radiochromic films. Homogeneously planned doses of 10 Gy were delivered to a box-like target volume in the homogeneous phantom and to two clinical scenarios with increasing complexity in the head phantom.ResultsFor all tests the mean of the local differences of the absolute dose to water determined with the alanine pellets compared to the predicted dose from the treatment planning system installed at the audited institution was determined. The mean value taken over all tests performed was −0.1 ± 1.0%. The measurements carried out with the ionization chamber were consistent with the dose determined by the alanine pellets with a mean deviation of −0.5 ± 0.6%.ConclusionThe developed dosimetry audit method was successfully applied at five proton centers including various “turn-key” Cyclotron solutions by IBA, Varian and Mevion. This independent audit with extension to other tumour sites and use of the correspondent anthropomorphic phantoms may be proposed as part of a credentialing procedure for future clinical trials in proton beam therapy.     

Étude de la dosimétrie in vivo par semi-conducteurs EPD-20 dans les conditions de l’irradiation corporelle totale

PurposeThe objective of this work was the study of in vivo dosimetry performed in a series of 54 patients receiving total body irradiation (TBI) at the Salah-Azaiz Institute of Tunis since 2004. In vivo dosimetry measurements were compared to analytically calculated doses from monitor units delivered.Patients and methodThe irradiation was conducted by a linear accelerator (Clinac^® 1800, Varian, Palo Alto, USA) using nominal X-rays energies of 6 MV and 18 MV, depending on the thickness of the patient at the abdomen. The dose was measured by semi-conductors p-type EPD-20. These diodes were calibrated in advance with an ionization chamber “PTW Farmer” type of 0.6 cm³ and were placed on the surface of plexiglas phantom in the same TBI conditions. A study of dosimetric characteristics of semi-conductors EPD-20 was carried out as a function of beam direction and temperature. Afterwards, we conducted a comparative analysis of doses measured using these detectors during irradiation to those calculated retrospectively from monitor units delivered to each patient conditioned by TBI.ResultsExperience showed that semi-conductors are sensitive to the angle of beam radiation (0–90°) and the temperature (22–40 °C). The maximum variation is respectively 5 and 7%, but in our irradiation conditions these correction factors are less than 1%. The analysis of the results of the in vivo dosimetry had shown that the ratio of the average measured doses and analytically calculated doses at the abdomen, mediastina, right lung and head are 1.005, 1.007, 1.0135 and 1.008 with a standard deviation “type A” respectively of 3.04, 2.37, 7.09 et 4.15%.ConclusionIn vivo dosimetry by semi-conductors is in perfect agreement with dosimetry by calculation. However, in vivo dosimetry using semiconductors is the only technique that can reflect the dose actually received instantly by the patient during TBI given the many factors that calculation can not take into account: patient and organs motions and the heterogeneity of the targets.     

Cardiac substructures exposure in left-sided breast cancer radiotherapy: Is the mean heart dose a reliable predictor of cardiac toxicity?

PurposeThis study aimed to assess radiation dose distribution to cardiac subvolumes in left-sided breast cancer radiotherapy (LBCRT) and to clarify whether the mean heart dose (MHD) reliably reflects cardiac substructures exposure.Materials and methodsFifty women referred for adjuvant LBCRT were prospectively evaluated. All patients received 3D-conformal hypofractionated radiotherapy (40 Gy delivered in 15 fractions of 2.67 Gy ± boost of 13.35 Gy). Cardiac substructures were contoured using the F. Duane's cardiac atlas. Dose distribution to cardiac chambers, left main (LM), left anterior descending (LAD), left circumflex (LCx) and right coronary artery (RCA)) was assessed. Dosimetric associations were analysed.ResultsThe mean MHD was 3.08 Gy (EQD2 = 3.67 Gy). The mean Dmean/Dmax LAD was 11.45 Gy (EQD2 = 13.64 Gy)/29.5 Gy (EQD2 = 35.15 Gy). Low doses were delivered to LM, LCx, and RCA (Dmean ≤ 1.3 Gy). The left ventricle (LV) was the most exposed cardiac chamber with Dmean/Dmax of 4.78 Gy/37 Gy. The strongest correlation with MHD was found for Dmean LAD (r = 0.81). For every 1 Gy increase in MHD, Dmean LAD rose by 3.4 Gy. However, the proportion of variance in Dmean LAD predictable from MHD was moderate (R² = 0.65). For all other cardiac substructures, R² values were < 0.7.ConclusionOur study showed high exposure of LAD and LV in LBCRT. With poor predictive value, MHD may underestimate doses to cardiac substructures. For optimal heart sparing radiotherapy, we recommend to consider LV and LAD as separate organ at risk.     

Stereotactic radiotherapy for large solitary brain metastases

PurposeTo assess effectiveness and toxicity levels of stereotactic radiation therapy without whole brain radiation therapy in patients with solitary brain metastases larger than 3 cm.Patients and methodsBetween June 2007 and March 2009, 12 patients received fractionated stereotactic radiation therapy and 24 patients underwent stereotactic radiosurgery. For the fractionated stereotactic radiation therapy group, 3 × 7.7 Gy were delivered to the planning target volume (PTV); median volume and diameter were 29.4 cm³ and 4.4 cm, respectively. For the stereotactic radiosurgery group, 14 Gy were delivered to the PTV; median volume and diameter were 15.6 cm³ and 3.7 cm, respectively.ResultsMedian follow-up was 218 days. For the fractionated stereotactic radiation therapy group, local control rates were 100% at 360 days and 64% at 720 days; for the stereotactic radiosurgery group, rates were 58% at 360 days and 48% at 720 days (P = 0.06). Median survival time was 504 days for the fractionated stereotactic radiation therapy group and 164 days for the stereotactic radiosurgery group (P = 0.049). Two cases of grade 2 toxicity were observed in the fractionated stereotactic radiation therapy group, and 6 cases of grade 1–2 toxicity, in the stereotactic radiosurgery group.ConclusionsThis study provides data to support that fractionated stereotactic radiation therapy without whole brain radiation therapy with a margin dose of 3 fractions of 7.7 Gy for treatment of solitary large brain metastases is efficient and well-tolerated. Because of the significant improvement in overall survival, this schedule should be assessed in a randomized trial.     

Comparison of dosimetric parameters and acute toxicity of intensity-modulated and three-dimensional radiotherapy in patients with cervix carcinoma: A randomized prospective study

PurposeThe use of intensity-modulated radiotherapy (IMRT) to treat cervix carcinoma has increased, however prospective randomized trials are still lacking.AimTo compare the dosimetric parameters and associated acute toxicity in patients with cervix carcinoma treated with three-dimensional (3D) conformal radiotherapy and IMRT.Patients and methodsForty patients were randomized in two arms each consisting of 20 patients. Patients in both arms received concurrent chemoradiation (cisplatin 40 mg/m² weekly; 50 Gy/25 fractions). Patients were treated with 3D conformal radiotherapy in one arm and with IMRT in another arm. After external beam radiotherapy, all patients received brachytherapy (21 Gy/3 fractions at weekly interval). For dosimetric comparison, both kinds of the plans were done for all the patients. All patients were assessed throughout and until 90 days after completion of treatment for acute gastrointestinal, genitourinary and hematologic toxicities.ResultsBoth plans achieved adequate planning target volume coverage, while mean conformity index was found significantly better in IMRT plans (P-value = 0.001). D₃₅ (dose to 35% volume) and D₅₀ for bladder was reduced by 14.62 and 32.57% and for rectum by 23.82 and 43.68% in IMRT. For IMRT, V₄₅ (volume receiving 45 Gy) of bowel were found significantly lesser (P-value = 0.0001), non-tumour integral dose was found significantly higher (P-value = 0.0240) and V₂₀ of bone marrow was found significantly reduced (P-value = 0.019) in comparison to that in 3D conformal radiotherapy. Significant reduction of grade 2 or more (20 vs 45%; P-value = 0.058) and grade ≥ 3 (5 vs 15%, P-value = 0.004) acute genitourinary toxicity and grade 2 or more (20 vs 45%, P-value = 0.003) and grade 3 or more (5 vs. 20%, P-value = 0.004) acute gastrointestinal toxicity while no significant difference for grade 2 and 3 or more haematological toxicity was noted in patients treated with IMRT compared to 3D conformal radiotherapy.ConclusionIMRT provide a good alternative for treatment of cervix carcinoma with lower acute gastrointestinal and acute genitourinary toxicity with similar target coverage compared to 3D conformal radiotherapy.     

Protontherapy versus best photon for mediastinal Hodgkin lymphoma: Dosimetry comparison and treatment using ILROG guidelines

The purpose of this work was reducing treatment-related toxicity for Hodgkin lymphomas using practical procedure inspired by the ILROG guidelines. Reporting the first case of localized Hodgkin lymphoma treated with protontherapy in France. A 24-year-old female with mediastinal, bulky, localized, mixed-cellularity, classic Hodgkin lymphoma required an involved-site radiation therapy after complete response following polychemotherapy. Three-dimensional conformal radiation therapy was not acceptable due to high doses to breasts, heart and lungs. We realized a four-dimensional computed tomography (CT) to evaluate target movements and another CT with gating and breath-hold technique. Delineation was performed on both CT using the initial fluorodeoxyglucose positron-emission tomography/CT. One dosimetric plan with rotational intensity-modulated radiation therapy with a helical Tomotherapy© was realized and compared to another one with conformational protontherapy. Ninety-five percent of the planning target volume was covered by 98 and 99% of the prescribed dose with protontherapy and helical Tomotherapy©. Protontherapy provided the best organ at risk protection. Lung and heart protections were better with protontherapy: lung mean dose (3.7 Gy vs. 8.4 Gy) and median dose (0.002 Gy vs. 6.9 Gy), heart mean dose (2.6 Gy vs. 3.7 Gy). Breast sparing was better for both breasts using protontherapy: right breast mean dose (2.4 Gy vs. 4.4 Gy) and left (1.9 Gy vs. 4.6 Gy). The biggest difference was seen with low doses, which were better with protontherapy: volume of lung receiving 5 Gy was 17.5% vs. 54.2% with Helical Tomotherapy©. In view of these results, we decided to treat our patient with protontherapy using respiratory assessment. We delivered 30 Gy (15 fractions) using protontherapy with one direct anterior field using pencil beam scanning and deep inspiration breath-hold technique. We observed only grade 1 skin erythema during treatment and no toxicity during early follow-up.     

Quel impact de la RCMI des carcinomes nasopharyngés sur les structures glandulaires ?

PurposeThe aim of this work is to evaluate the anatomical changes of the glandular structures during the NPC IMRT and to study their dosimetric impacts.Patients and methodsTwenty patients receiving IMRT for NPC were included. For each patient, a second dosimetric CT was performed at a dose of 38 Gy, which was fused with the initial planning dosimetric CT. We calculated the volume percent change, the positional and dosimetric variation between the 2 scanners for the glandular structures (parotid, submaxillary, thyroid and pituitary).ResultsWe observed a decrease in the volume of right and left parotids (− 27.9% and − 27.54%). It was correlated with the initial dose planned at its level. For the sub maxillary glands, the decrease was − 36.1% on the right and − 27.28% on the left. The value of reduction of the thyroid gland was − 18.01%. A medial supra-millimeter migration of 2 and 1.15 mm was found for right and left parotid glands respectively, correlated with GTV N reduction volume. We found a significant increase in mean doses for the parotid glands. It was 1.8 ± 2.3 Gy for the right and 1.5 ± 2.7 Gy for the left. For the right sub maxillary gland, the increase was about 0.35 ± 2 Gy and 3.79 ± 5.2 Gy for the thyroid.ConclusionThe modifications observed for glandular structures during NPC IMRT can explain the different toxicities caused by radiation. It seems also that a careful adaptation of the treatment plan should be considered during therapy.