A review of uncertainties in radiotherapy dose reconstruction and their impacts on dose-response relationships.

Proper understanding of the risk of radiation-induced late effects for patients receiving external photon beam radiotherapy requires the determination of reliable dose-response relationships. Although significant efforts have been devoted to improving dose estimates for the study of late effects, the most often questioned explanatory variable is still the dose. In this work, based on a literature review, we provide an in-depth description of the radiotherapy dose reconstruction process for the study of late effects. In particular, we focus on the identification of the main sources of dose uncertainty involved in this process and summarise their impacts on the dose-response relationship for radiotherapy late effects. We provide a number of recommendations for making progress in estimating the uncertainties in current studies of radiotherapy late effects and reducing these uncertainties in future studies.

Evaluation of MVCT imaging dose levels during helical IGRT: comparison between ion chamber, TLD, and EBT3 films.

The purpose of this investigation was to evaluate the dose on megavoltage CT (MVCT) images required for tomotherapy. As imaging possibilities are often used before each treatment and usually used several times before the session, we tried to evaluate the dose delivered during the procedure. For each scanning mode (fine, normal, and coarse), we first established the relative variation of these doses according to different technical parameters (explored length, patient setup). These dose variations measured with the TomoPhant, also known as Cheese phantom, showed the expected variations (due to the variation of scattered radiation) of 15% according to the explored length and ± 5% according to the phantom setup (due to the variation of the point of measurement in the bore). In order to estimate patient doses, an anthropomorphic phantom was used for thermoluminescent and film dosimetry. The degree of agreement between the two methods was very satisfactory (the differences correspond to 5 mGy per imaging session) for the three sites studied (head & neck, thorax, and abdomen). These measurements allowed us to estimate the delivered dose of between 1 cGy and 4 cGy according to the site and imaging mode. Finally, we attempted to investigate a way to calculate this delivered dose in our patients from the study conducted on a cylindrical phantom and by taking into account data from the initial kV-CT scan. The results we obtained were close to our measurements, with discrepancies below 5 mGy per MVCT.

Clinical outcomes of definitive chemoradiation followed by intracavitary pulsed-dose rate image-guided adaptive brachytherapy in locally advanced cervical cancer.

OBJECTIVE: To report the outcomes and late toxicities of patients with locally advanced cervical cancer treated with concomitant chemoradiation (CRT) followed by intracavitary image-guided adaptive brachytherapy (IGABT). METHODS: Data from consecutive patients with histologically proven stage IB-IVA cervical cancer treated with curative intent in a single institution were analyzed. After pelvic +/- para-aortic external-beam radiation therapy, they received pulsed-dose rate IGABT following GEC-ESTRO recommendations. RESULTS: Two hundred and twenty-five patients were enrolled. Sixty-five percent were stage≥IIB according to FIGO classification. Ninety-five percent received CRT. Mean D90 to HR and IR-CTV were 80.4+/-10.3Gy and 67.7+/-6.1Gy. After a median follow-up of 38.8months, 3-year local control and overall survival rates were 86.4% and 76.1%, respectively. A trend for a detrimental effect of tumor stage on local control rates was observed with 3-year local control rates of 100% for stages IB1 and IIA, 90.5 for IB2, 85.8% for IIB, 50% for IIIA, 77.1 for IIIB, and 66.7% for IVA tumors (p=0.06). Local control rates at 3years were 95.6% in the group of patients with D90 of HR-CTV≥85Gy, 88.8% in those with D90 between 80 and 85Gy, and 80% when D90<80Gy (p=0.018). Eighteen severe late gastrointestinal and urinary effects affecting 14 patients were reported corresponding with a crude incidence of 6.6%. CONCLUSIONS: CRT followed by IGABT provides high local control rates with limited toxicity. Reaching high doses is mandatory to achieve local control and interstitial brachytherapy is necessary in advanced diseases.

Experimental assessment of out-of-field dose components in high energy electron beams used in external beam radiotherapy.

The purpose of this work was to experimentally investigate the out-of-field dose in a water phantom, with several high energy electron beams used in external beam radiotherapy (RT). The study was carried out for 6, 9, 12, and 18 MeV electron beams, on three different linear accelerators, each equipped with a specific applicator. Measurements were performed in a water phantom, at different depths, for different applicator sizes, and off-axis distances up to 70 cm from beam central axis (CAX). Thermoluminescent powder dosimeters (TLD-700) were used. For given cases, TLD measurements were compared to EBT3 films and parallel-plane ionization chamber measurements. Also, out-of-field doses at 10 cm depth, with and without applicator, were evaluated. With the Siemens applicators, a peak dose appears at about 12-15 cm out of the field edge, at 1 cm depth, for all field sizes and energies. For the Siemens Primus, with a 10 × 10 cm(²) applicator, this peak reaches 2.3%, 1%, 0.9% and 1.3% of the maximum central axis dose (Dmax) for 6, 9, 12 and 18 MeV electron beams, respectively. For the Siemens Oncor, with a 10 × 10 cm(²) applicator, this peak dose reaches 0.8%, 1%, 1.4%, and 1.6% of Dmax for 6, 9, 12, and 14 MeV, respectively, and these values increase with applicator size. For the Varian 2300C/D, the doses at 12.5 cm out of the field edge are 0.3%, 0.6%, 0.5%, and 1.1% of Dmax for 6, 9, 12, and 18 MeV, respectively, and increase with applicator size. No peak dose is evidenced for the Varian applicator for these energies. In summary, the out-of-field dose from electron beams increases with the beam energy and the applicator size, and decreases with the distance from the beam central axis and the depth in water. It also considerably depends on the applicator types. Our results can be of interest for the dose estimations delivered in healthy tissues outside the treatment field for the RT patient, as well as in studies exploring RT long-term effects.

Risk of second bone sarcoma following childhood cancer: role of radiation therapy treatment.

Bone sarcoma as a second malignancy is rare but highly fatal. The present knowledge about radiation-absorbed organ dose-response is insufficient to predict the risks induced by radiation therapy techniques. The objective of the present study was to assess the treatment-induced risk for bone sarcoma following a childhood cancer and particularly the related risk of radiotherapy. Therefore, a retrospective cohort of 4,171 survivors of a solid childhood cancer treated between 1942 and 1986 in France and Britain has been followed prospectively. We collected detailed information on treatments received during childhood cancer. Additionally, an innovative methodology has been developed to evaluate the dose-response relationship between bone sarcoma and radiation dose throughout this cohort. The median follow-up was 26 years, and 39 patients had developed bone sarcoma. It was found that the overall incidence was 45-fold higher [standardized incidence ratio 44.8, 95 % confidence interval (CI) 31.0-59.8] than expected from the general population, and the absolute excess risk was 35.1 per 100,000 person-years (95 % CI 24.0-47.1). The risk of bone sarcoma increased slowly up to a cumulative radiation organ absorbed dose of 15 Gy [hazard ratio (HR) = 8.2, 95 % CI 1.6-42.9] and then strongly increased for higher radiation doses (HR for 30 Gy or more 117.9, 95 % CI 36.5-380.6), compared with patients not treated with radiotherapy. A linear model with an excess relative risk per Gy of 1.77 (95 % CI 0.6213-5.935) provided a close fit to the data. These findings have important therapeutic implications: Lowering the radiation dose to the bones should reduce the incidence of secondary bone sarcomas. Other therapeutic solutions should be preferred to radiotherapy in bone sarcoma-sensitive areas.

Breast cancer following radiotherapy for a hemangioma during childhood.

PURPOSE: A cohort study was performed to investigate the carcinogenic effect of treatment of skin hemangioma with ionizing radiation in early childhood. This paper presents the incidence of breast cancer (BC) in this cohort and its association with radiotherapy. METHODS AND MATERIALS: In an incidence study, 3,316 women treated for a skin hemangioma between 1941 and 1977 at the Institut Gustave-Roussy were included, among whom 2,697 had received radiotherapy. The mean age at first exposure was 0.7 years, and the mean absorbed dose to the breast was 70 mGy. Treatment reconstruction and the estimation of radiation doses delivered to the breast were obtained for 92% of the women who had received radiotherapy. External and internal analyses were performed. RESULTS: During an average follow-up of 35 years, a total of 17 women developed an invasive BC, compared to 7.5 expected in the French general population (SIR = 2.3, 95% CI, 1.4-3.5), and the absolute excess risk strongly increased with attained age. Compared to individuals with no radiotherapy, the risk of BC increased with increasing radiation dose with RRs of 3.2, 6.3, and 8.0 for dose categories of >0-10, 10-100, and >100 mGy, respectively; however, dose-response relationship was not significant. CONCLUSION: This study confirms that radiation treatment performed in the past for hemangioma during childhood increases the risk of BC.

Interfractional set-up errors evaluation by daily electronic portal imaging of IMRT in head and neck cancer patients.

INTRODUCTION: Interfractional set-up errors were assessed from daily portal images (PI) registration for head and neck cancer patients. We aimed to evaluate whether a daily PI is worthwhile and we derived the Planning Target Volume (PTV) margins from the estimation of systematic and random errors. MATERIAL AND METHODS: Twenty patients were treated in supine position with a fixed 5-point mask immobilisation system and head-and-knee supports. DRRs (Digitally Reconstructed Radiograph) were obtained from the planning CT-scan and considered the reference images to be compared with two orthogonal PI by matching bone anatomy landmarks. A total of 567 PI were done. For the set-up errors analysis, we determined the systematic, random, and overall standard deviations (SD), as well as the overall means in three directions (cranio caudal CC, medio lateral ML and anterior posterior AP). PTV-margins were calculated according to three methods. Differences of SD regarding the overall displacements among portals performed every day and each 2, 3, or 4 days were tested. RESULTS: The systematic set-up errors were less than 1 mm in the three directions whereas the random set-up errors were around 2 mm. PTV margins varied from 3 to 4 mm in the 3 directions. Corrections were significant in the CC direction only, in which the set-up error increased significantly when the scenario of one PI every 3 fractions was adopted. CONCLUSIONS: It is of practical importance to apply on-line protocols with contouring of the bony landmarks on the PI in order to decrease the systematic mean error in this patient group. This study suggested that a PI in AP and ML directions once a week and every two days in the CC direction would be adequate to overcome the problem of set-up errors.

Risk of a second malignant neoplasm after cancer in childhood treated with radiotherapy: correlation with the integral dose restricted to the irradiated fields.

PURPOSE: After successful treatment of cancers in childhood, the occurrence of second malignant neoplasm (SMN) came to the fore. Few studies have considered the relationship between the radiation dose received and the risk of developing an SMN. To take into account the heterogeneity of the dose distribution so as to evaluate the overall risk of an SMN after a childhood cancer, we therefore focused on the integral dose restricted to the irradiated fields. METHODS AND MATERIALS: The study was performed in a cohort of 4,401 patients who were 3-year survivors of all types of childhood cancer treated between 1947 and 1986 in France and Great Britain. For each patient, the integral dose was estimated for the volume inside the beam edges. RESULTS: We found a significant dose-response relationship between the overall risk of an SMN and the estimated integral dose. The excess relative risk for each incremental unit of the integral dose was only 0.008 in a linear model and 0.017 when a negative exponential term was considered, when adjusted for chemotherapy. The risk of SMN occurrence was 2.6 times higher in the case of irradiation. However among patients who had received radiotherapy, only those who had received the highest integral dose actually had a higher risk. CONCLUSIONS: The integral dose in our study cannot be considered as a good predictor of later risks. However other studies with the same study design are obviously needed to evaluate the use of the integral dose as a tool for decision making concerning different radiotherapy techniques.

Evaluation of an atlas-based automatic segmentation software for the delineation of brain organs at risk in a radiation therapy clinical context.

BACKGROUND AND PURPOSE: Conformal radiation therapy techniques require the delineation of volumes of interest, a time-consuming and operator-dependent task. In this work, we aimed to evaluate the potential interest of an atlas-based automatic segmentation software (ABAS) of brain organs at risk (OAR), when used under our clinical conditions. MATERIALS AND METHODS: Automatic and manual segmentations of the eyes, optic nerves, optic chiasm, pituitary gland, brain stem and cerebellum of 11 patients on T1-weighted magnetic resonance, 3-mm thick slice images were compared using the Dice similarity coefficient (DSC). The sensitivity and specificity of the ABAS were also computed and analysed from a radiotherapy point of view by splitting the ROC (Receiver Operating Characteristic) space into four sub-regions. RESULTS: Automatic segmentation of OAR was achieved in 7-8 min. Excellent agreement was obtained between automatic and manual delineations for organs exceeding 7 cm3: the DSC was greater than 0.8. For smaller structures, the DSC was lower than 0.41. CONCLUSIONS: These tests demonstrated that this ABAS is a robust and reliable tool for automatic delineation of large structures under clinical conditions in our daily practice, even though the small structures must continue to be delineated manually by an expert.

Comparison of dose contribution to normal pelvic tissues among conventional, conformal and intensity-modulated radiotherapy techniques in prostate cancer.

High-energy external radiotherapy has become one of the most common treatment in localized prostate cancer. We compared the difference of dose distribution, mainly at the 5-30 Gy dose level, in the irradiated pelvic volume among three modalities of radiotherapy for patients with prostate cancer: conventional, conformal and intensity-modulated radiotherapy (IMRT). We selected six patients with prostate cancer treated by conformal radiotherapy at the doses of 46 Gy to PTVN (prostate and seminal vesicles), and 70 Gy to PTV-T (prostate). The conventional technique": an 8-field arrangement was used; the conformal technique 4 fields with a boost through 6 fields. For IMRT, a five-beam arrangement was used. Dose-volume histograms (DVH) were analyzed and compared among the three techniques. The IMRT technique significantly increased the pelvic volume covered by the isodose surfaces below 15 Gy as compared with the conventional and conformal techniques. The mean absolute increase for the pelvic volume included between 5-30 Gy for the IMRT technique, was about 2 900 ml as compared with the conventional technique. However, IMRT significantly reduced the irradiated volume of the rectum in the dose range of 5 to 40 Gy, also significantly reduced the irradiated volume of bladder and femoral heads, and obtained a similar or improved isodose distribution in the PTVs. In addition, the use of IMRT slightly increased the relative dose delivered to the body volume outside the pelvis, as estimated by the use of specific software. A long-term follow-up will be needed to evaluate potential late treatment complications related to the use of IMRT and the low or moderate irradiation dose level obtained in the pelvis and in the whole body.

Inverse planning approach for 3-D MRI-based pulse-dose rate intracavitary brachytherapy in cervix cancer.

PURPOSE: The purpose of this study was to evaluate the inverse planning simulated annealing (IPSA) software for the optimization of dose distribution in patients with cervix carcinoma treated with MRI-based pulsed-dose rate intracavitary brachytherapy. METHODS AND MATERIALS: Thirty patients treated with a technique using a customized vaginal mold were selected. Dose-volume parameters obtained using the IPSA method were compared with the classic manual optimization method (MOM). Target volumes and organs at risk were delineated according to the Gynecological Brachytherapy Group/European Society for Therapeutic Radiology and Oncology recommendations. Because the pulsed dose rate program was based on clinical experience with low dose rate, dwell time values were required to be as homogeneous as possible. To achieve this goal, different modifications of the IPSA program were applied. RESULTS: The first dose distribution calculated by the IPSA algorithm proposed a heterogeneous distribution of dwell time positions. The mean D90, D100, and V100 calculated with both methods did not differ significantly when the constraints were applied. For the bladder, doses calculated at the ICRU reference point derived from the MOM differed significantly from the doses calculated by the IPSA method (mean, 58.4 vs. 55 Gy respectively; p = 0.0001). For the rectum, the doses calculated at the ICRU reference point were also significantly lower with the IPSA method. CONCLUSIONS: The inverse planning method provided fast and automatic solutions for the optimization of dose distribution. However, the straightforward use of IPSA generated significant heterogeneity in dwell time values. Caution is therefore recommended in the use of inverse optimization tools with clinical relevance study of new dosimetric rules.

Locally advanced cervical cancer: Is it relevant to report image-guided adaptive brachytherapy using point A dose?

PURPOSE: To evaluate the usefulness of reporting the point A dose in patients with locally advanced cervical cancer treated with image-guided adaptive brachytherapy (IGABT). METHODS AND MATERIALS: Dosimetric data from patients treated with a combination of chemoradiation and intracavitary IGABT were examined in light of their outcomes. Prescribing followed the Groupe Européen de Curiethérapie-European Society for Radiation Oncology recommendations. All doses were converted in 2-Gy equivalent. The relationships between the D90 high-risk clinical target volume (CTVHR) and intermediate-risk clinical target volume (CTVIR) and point A doses were studied. Dose-effect relationships based on the probit model and log-rank test were assessed. RESULTS: Two hundred twelve patients were included with a median followup of 53.0 months. A total of 28 local relapses were reported, resulting in a local control rate of 86.6% at 3 years. Mean D90 CTVHR, CTVIR, and point A doses were: 79.7 ± 10.4 Gy, 67.4 ± 5.8 Gy, and 66.4 ± 5.6 Gy, respectively. The mean D90 were significantly different and independent from the mean point A dose, even in bulky tumors at diagnosis or in large CTVHR lesions. Point A dose appeared correlated with TRAK, and finally with the D90 CTVHR through a complex formula including the CTVHR volume (R2 = 0.55). Whereas significant relationships between the probability of achieving local control and the D90 CTVHR and CTVIR (p = 0.08 and 0.025) were observed, no similar relationship was found with point A dose except a trend of an inverse relation. After sorting patients according to three dose levels, highest local control rates were observed in patients with D90 CTVHR ≥85 Gy, whereas those with point A doses ≥70 Gy had the worst outcomes. CONCLUSIONS: In patients treated with IGABT, point A dose is not predictive of local control but a surrogate of the irradiated volume. Its relationships with the D90 CTVHR are indirect and complex rising the question of relevance of its reporting in routine.

Relationships between Regional Radiation Doses and Cognitive Decline in Children Treated with Cranio-Spinal Irradiation for Posterior Fossa Tumors.

Pediatric posterior fossa tumor (PFT) survivors who have been treated with cranial radiation therapy often suffer from cognitive impairments that might relate to IQ decline. Radiotherapy (RT) distinctly affects brain regions involved in different cognitive functions. However, the relative contribution of regional irradiation to the different cognitive impairments still remains unclear. We investigated the relationships between the changes in different cognitive scores and radiation dose distribution in 30 children treated for a PFT. Our exploratory analysis was based on a principal component analysis (PCA) and an ordinary least square regression approach. The use of a PCA was an innovative way to cluster correlated irradiated regions due to similar radiation therapy protocols across patients. Our results suggest an association between working memory decline and a high dose (equivalent uniform dose, EUD) delivered to the orbitofrontal regions, whereas the decline of processing speed seemed more related to EUD in the temporal lobes and posterior fossa. To identify regional effects of RT on cognitive functions may help to propose a rehabilitation program adapted to the risk of cognitive impairment.

Is intensity-modulated radiotherapy better than conventional radiation treatment and three-dimensional conformal radiotherapy for mediastinal masses in patients with Hodgkin's disease, and is there a role for beam orientation optimization and dose constraints assigned to virtual volumes?

PURPOSE: To evaluate the role of beam orientation optimization and the role of virtual volumes (VVs) aimed at protecting adjacent organs at risk (OARs), and to compare various intensity-modulated radiotherapy (IMRT) setups with conventional treatment with anterior and posterior fields and three-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: Patients with mediastinal masses in Hodgkin's disease were treated with combined modality therapy (three to six cycles of adriamycin, bleomycin, vinblastine, and dacarbazine [ABVD] before radiation treatment). Contouring and treatment planning were performed with Somavision and CadPlan Helios (Varian Systems, Palo Alto, CA). The gross tumor volume was determined according to the prechemotherapy length and the postchemotherapy width of the mediastinal tumor mass. A 10-mm isotropic margin was added for the planning target volume (PTV). Because dose constraints assigned to OARs led to unsatisfactory PTV coverage, VVs were designed for each patient to protect adjacent OARs. The prescribed dose was 40 Gy to the PTV, delivered according to guidelines from International Commission on Radiation Units and Measurements Report No. 50. Five different IMRT treatment plans were compared with conventional treatment and 3D-CRT. RESULTS: Beam orientation was important with respect to the amount of irradiated normal tissues. The best compromise in terms of PTV coverage and protection of normal tissues was obtained with five equally spaced beams (5FEQ IMRT plan) using dose constraints assigned to VVs. When IMRT treatment plans were compared with conventional treatment and 3D-CRT, dose conformation with IMRT was significantly better, with greater protection of the heart, coronary arteries, esophagus, and spinal cord. The lungs and breasts in women received a slightly higher radiation dose with IMRT compared with conventional treatments. The greater volume of normal tissue receiving low radiation doses could be a cause for concern. CONCLUSIONS: The 5FEQ IMRT plan with dose constraints assigned to the PTV and VV allows better dose conformation than conventional treatment and 3D-CRT, notably with better protection of the heart and coronary arteries. Of concern is the "spreading out" of low doses to the rest of the patient's body.

Tumor dose-volume response in image-guided adaptive brachytherapy for cervical cancer: A meta-regression analysis.

PURPOSE: Image-guided adaptive brachytherapy is a high precision technique that allows dose escalation and adaptation to tumor response. Two monocentric studies reported continuous dose-volume response relationships, however, burdened by large confidence intervals. The aim was to refine these estimations by performing a meta-regression analysis based on published series. METHODS AND MATERIALS: Eligibility was limited to series reporting dosimetric parameters according to the Groupe Européen de Curiethérapie-European SocieTy for Radiation Oncology recommendations. The local control rates reported at 2-3 years were confronted to the mean D90 clinical target volume (CTV) in 2-Gy equivalent using the probit model. The impact of each series on the relationships was pondered according to the number of patients reported. RESULTS: An exhaustive literature search retrieved 13 series reporting on 1299 patients. D90 high-risk CTV ranged from 70.9 to 93.1 Gy. The probit model showed a significant correlation between the D90 and the probability of achieving local control (p < 0.0001). The D90 associated to a 90% probability of achieving local control was 81.4 Gy (78.3-83.8 Gy). The planning aim of 90 Gy corresponded to a 95.0% probability (92.8-96.3%). For the intermediate-risk CTV, less data were available, with 873 patients from eight institutions. Reported mean D90 intermediate-risk CTV ranged from 61.7 to 69.1 Gy. A significant dose-volume effect was observed (p = 0.009). The D90 of 60 Gy was associated to a 79.4% (60.2-86.0%) local control probability. CONCLUSION: Based on published data from a high number of patients, significant dose-volume effect relationships were confirmed and refined between the D90 of both CTV and the probability of achieving local control. Further studies based on individual data are required to develop nomograms including nondosimetric prognostic criteria.

Vaginal dose assessment in image-guided brachytherapy for cervical cancer: Can we really rely on dose-point evaluation?

PURPOSE: Although dose-volume parameters in image-guided brachytherapy have become a standard, the use of posterior-inferior border of the pubic symphysis (PIBS) points has been recently proposed in the reporting of vaginal doses. The aim was to evaluate their pertinence. METHODS AND MATERIALS: Nineteen patients who received image-guided brachytherapy after concurrent radiochemotherapy were included. Per treatment, CT scans were performed at Days 2 and 3, with reporting of the initial dwell positions and times. Doses delivered to the PIBS points were evaluated on each plan, considering that they were representative of one-third of the treatment. The movements of the applicator according to the PIBS point were analysed. RESULTS: Mean prescribed doses at PIBS -2, PIBS, PIBS +2 were, respectively, 2.23 ± 1.4, 6.39 ± 6.6, and 31.85 ± 36.06 Gy. Significant differences were observed between the 5 patients with vaginal involvement and the remaining 14 at the level of PIBS +2 and PIBS: +47.60 Gy and +7.46 Gy, respectively (p = 0.023 and 0.03). The variations between delivered and prescribed doses at PIBS points were not significant. However, at International commission on radiation units and measurements rectovaginal point, the delivered dose was decreased by 1.43 ± 2.49 Gy from the planned dose (p = 0.019). The delivered doses at the four points were strongly correlated with the prescribed doses with R(2) ranging from 0.93 to 0.95. The movements of the applicator in regard of the PIBS point assessed with the Digital Imaging and Communications in Medicine coordinates were insignificant. CONCLUSION: The doses evaluated at PIBS points are not impacted by intrafractional movements. PIBS and PIBS +2 dose points allow distinguishing the plans of patients with vaginal infiltration. Further studies are needed to correlate these parameters with vaginal morbidity.

Field size dependent mapping of medical linear accelerator radiation leakage.

The purpose of this study was to investigate the suitability of a graphics library based model for the assessment of linear accelerator radiation leakage. Transmission through the shielding elements was evaluated using the build-up factor corrected exponential attenuation law and the contribution from the electron guide was estimated using the approximation of a linear isotropic radioactive source. Model parameters were estimated by a fitting series of thermoluminescent dosimeter leakage measurements, achieved up to 100 cm from the beam central axis along three directions. The distribution of leakage data at the patient plane reflected the architecture of the shielding elements. Thus, the maximum leakage dose was found under the collimator when only one jaw shielded the primary beam and was about 0.08% of the dose at isocentre. Overall, we observe that the main contributor to leakage dose according to our model was the electron beam guide. Concerning the discrepancies between the measurements used to calibrate the model and the calculations from the model, the average difference was about 7%. Finally, graphics library modelling is a readily and suitable way to estimate leakage dose distribution on a personal computer. Such data could be useful for dosimetric evaluations in late effect studies.

D2cm³/DICRU ratio as a surrogate of bladder hotspots localizations during image-guided adaptive brachytherapy for cervical cancer: assessment and implications in late urinary morbidity analysis.

PURPOSE: To evaluate the efficiency and potential implications of the lowest dose evaluated in the maximally exposed 2cm(3) of the bladder/dose evaluated at the International Commission for Radiation Units and Measurements (ICRU) bladder point (D2cm(3)/DICRU) ratio as surrogate to locate the D2cm(3) in patients treated with MRI-guided adaptive brachytherapy for cervical cancer. METHODS AND MATERIALS: The D2cm(3) area of the bladder was located in 69 patients, using the Digital Imaging and Communications in Medicine coordinates of its barycenter, with respect to the ICRU bladder point. The D2cm(3)/DICRU ratio was correlated with the longitudinal coordinate of the D2cm(3). Afterward, the ratio was used in a retrospective cohort of 216 patients to evaluate its impact in dose-effect analyses for late urinary incontinence. RESULTS: The mean position of the D2cm(3) was 1.73±0.98 cm cranially, 0.59±0.65 cm backwardly, and 0.02±0.89 cm to the right of the ICRU point. It was located above the ICRU point in 95.7% of the patients. Its position was lower in patients with vaginal involvement at diagnosis (p=0.03). The D2cm(3)/DICRU ratio was correlated with the position of the D2cm(3) (R²=0.716, p<10(-6)). In speculating that a ratio greater than one would predict a D2cm(3) located above the ICRU point, the sensibility, specificity, positive, and negative predictive values were 95.2%, 100%, 100%, and 66.8%, respectively. Among the retrospective cohort, 85 patients had a ratio lower than 1.1, reflecting a D2cm(3) located in the lower bladder. In these patients, analyses showed significant dose relationship with Grade 2-4 incontinence (p=0.017), whereas no correlation was demonstrated in the remaining patients. CONCLUSIONS: The D2cm(3)/DICRU ratio is a relevant surrogate to estimate the localization of the D2cm(3). Significant dose-effect correlations for incontinence were established in patients with low values for this ratio.

Intrafractional organs movement in three-dimensional image-guided adaptive pulsed-dose-rate cervical cancer brachytherapy: assessment and dosimetric impact.

PURPOSE: To prospectively evaluate the intrafractional movements of organs at risk (OARs) and their dosimetric impact during the delivery of pulsed-dose-rate brachytherapy in cervical cancer. PATIENTS AND METHODS: An MRI on Day 1 was used for treatment planning in 19 patients. CT scans were acquired at Days 1, 2, and 3 with delineation of the OARs. The MRI plan was transferred to each CT. The intersection volume between the 10 Gy isodose and the OARs were monitored, reflecting movement. Lower dose evaluated in the maximally exposed 0.1 cm(3) of an organ and lower dose evaluated in the maximally exposed 2 cm(3) of an organ (D(2cm3)) were evaluated on each CT and compared. Results were averaged considering that each CT reflected one-third of the treatment course to evaluate the delivered dose. RESULTS: No major movements of the sigmoid and bladder were observed, whereas the rectum got significantly closer to the implant at Day 2. The consequence was an increase of 6% ± 5.3 (3.7 Gy, α/ß = 3 Gy) of the delivered D(2cm3) from the planned dose, in contrast to 0.2% ± 6.1 for the bladder and 1.1% ± 6.4 for the sigmoid. The increase of the D(2cm3) of the rectum was reported in 17 patients, ranging from 0.4 to 9.4 Gy, leading to a 10.5% overcoming of the dose constraint (75 Gy). Similar tendencies were reported for lower dose evaluated in the maximally exposed 0.1 cm(3) of an organ. CONCLUSIONS: A significant systematic variation was observed for the rectum (+3.7 Gy). As significant random variations were observed, caution should be exercised when the planned D(2cm3) is close to the dose constraints.

Impact of treatment time and dose escalation on local control in locally advanced cervical cancer treated by chemoradiation and image-guided pulsed-dose rate adaptive brachytherapy.

PURPOSE: To report the prognostic factors for local control in patients treated for locally advanced cervical cancer with image guided pulsed-dose rate brachytherapy. MATERIALS/METHODS: Patients treated with curative intent by a combination of external beam radiotherapy and pulsed-dose rate brachytherapy were selected. Local failure was defined as any relapse in the cervix, vagina, parametria, or uterus during follow-up. Prognostic factors were selected based on log rank tests and then analyzed with a Cox model. Dose/effect correlations were performed using the probit model. RESULTS: Two hundred and twenty-five patients treated from 2006 to 2011 were included. According to the FIGO classification, 29% were stage IB, 58% stage II, 10% stage III, and 3% stage IVA; 95% received concomitant chemotherapy. Thirty patients were considered having incomplete response or local failure. Among the selected parameters, D90 for HR-CTV, D90 for IR-CTV, the overall treatment time, the TRAK, and the HR-CTV volume appeared significantly correlated with local control in univariate analysis. In multivariate analysis, overall treatment time >55days and HR-CTV volume >30cm(3) appeared as independent. The probit analysis showed significant correlations between the D90 for both CTVs, and the probability of achieving local control (p=0.008 and 0.024). The thresholds to reach to warrant a probability of 90% of local control were 85Gy to the D90 of the HR-CTV and 75Gy to 90% of the IR-CTV (in 2Gy equivalent, α/ß=10). To warrant the same local control rate, the D90 HR-CTV should be significantly increased in stage III-IV tumors, in case of HR-CTV >30cm(3), excessive treatment time, or tumor width at diagnosis >5cm (97, 92, 105, and 92Gy respectively). CONCLUSIONS: Overall treatment time and HR-CTV volume were independent prognostic factors for local control. The D90 for HR and IR CTV were significantly correlated with local control, and D90 HR-CTV should be adapted to clinical criteria.