Discontinuous stereotactic body radiotherapy schedule increases overall survival in early-stage non-small cell lung cancer.

OBJECTIVES: The duration of stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) may affect patient outcomes. We aimed to determine the impact of a continuous versus discontinuous SBRT schedule on local control (LC) and overall survival (OS) in NSCLC patients. MATERIALS AND METHODS: Consecutive NSCLC stage I patients (475) treated with SBRT in four centers were retrospectively analyzed. The delivered dose ranged from 48 to 75 Gy in 3-10 fractions. Based on the ratio between the treatment duration (TD) and number of fractions (n), patients were divided into two groups: continuous schedule (CS) (TD ≤ 1.6n; 239 patients) and discontinuous schedule (DS) (TD > 1.6n; 236 patients). LC and OS were compared using Cox regression analyses after propensity score matching (216 pairs). RESULTS: The median follow-up period was 41 months. Multivariate analysis showed that the DS (hazard ratio (HR): 0.42; 95 % confidence interval (CI): 0.22-0.78) and number of fractions (HR: 1.24; 95 % CI: 1.07-1.43) were significantly associated with LC. The DS (HR: 0.67; 95 % CI: 0.51-0.89), age (HR: 1.02; 95 % CI: 1-1.03), WHO performance status (HR: 2.27; 95 % CI: 1.39-3.7), and T stage (HR: 1.4; 95 % CI: 1.03-1.87) were significantly associated with OS. The 3-year LC and OS were 92 % and 64 % and 81 % and 53 % for DS and CS treatments, respectively (p < 0.01). Cox analysis confirmed that the discontinuous SBRT schedule significantly increased LC and OS. CONCLUSION: DS is associated with significantly improved LC and OS in early-stage NSCLC patients treated with SBRT.

Review of clinical applications of radiation-enhancing nanoparticles.

PURPOSE: Clinical evidence of the radiation-enhancing effects of nanoparticles has emerged. MATERIALS AND METHODS: We searched the literature in English and French on PubMed up to October 2019. The search term was "nanoparticle" AND "radiotherapy", yielding 1270 results. RESULTS: The two main NP used in clinical trials were hafnium oxide and gadolinium involving a total of 229 patients. Hafnium oxide NP were used in three phase 1/2 trials on sarcoma, head and neck squamous cell carcinoma or liver cancer and one phase 2/3 trial. There are six ongoing phase 1/2 clinical trials to evaluate the combination of gadolinium-based NP and RT for the treatment of brain metastases and cervical cancer. CONCLUSION: So far, intratumoral hafnium oxide nanoparticles were safe and improved efficacy in locally advanced sarcoma.

ITV versus mid-ventilation for treatment planning in lung SBRT: a comparison of target coverage and PTV adequacy by using in-treatment 4D cone beam CT.

BACKGROUND: The internal target volume (ITV) approach and the mid-ventilation (MidV) concept are the two main respiratory motion-management strategies under free breathing. The purpose of this work was to compare the actual in-treatment target coverage during volumetric modulated arctherapy (VMAT) delivered through both ITV-based and MidV-based planning target volume (PTV) and to provide knowledge in choosing the optimal PTV for stereotactic body radiotherapy (SBRT) for lung lesions. METHODS AND MATERIALS: Thirty-two lung cancer patients treated by a VMAT technique were included in the study. For each fraction, the mean time-weighted position of the target was localized by using a 4-dimensional cone-beam CT (4D-CBCT)-based image guidance procedure. The respiratory-correlated location of the gross tumor volume (GTV) during treatment delivery was determined for each fraction by using in-treatment 4D-CBCT images acquired concurrently with VMAT delivery (4D-CBCTin-treat). The GTV was delineated from each of the ten respiratory phase-sorted 4D-CBCTin-treat datasets for each fraction. We defined target coverage as the average percentage of the GTV included within the PTV during the patient's breathing cycle averaged over the treatment course. Target coverage and PTVs were reported for a MidV-based PTV (PTVMidV) using dose-probabilistic margins and three ITV-based PTVs using isotropic margins of 5 mm (PTVITV + 5mm), 4 mm (PTVITV + 4mm) and 3 mm (PTVITV + 3mm). The in-treatment baseline displacements and target motion amplitudes were reported to evaluate the impact of both parameters on target coverage. RESULTS: Overall, 100 4D-CBCTin-treat images were analyzed. The mean target coverage was 98.6, 99.6, 98.9 and 97.2% for PTVMidV, PTVITV + 5mm, PTVITV + 4mm and PTVITV + 3mm, respectively. All the PTV margins led to a target coverage per treatment higher than 95% in at least 90% of the evaluated cases. Compared to PTVITV + 5mm, PTVMidV, PTVITV + 4mm and PTVITV + 3mm had mean PTV reductions of 16, 19 and 33%, respectively. CONCLUSION: When implementing VMAT with 4D-CBCT-based image guidance, an ITV-based approach with a tighter margin than the commonly used 5 mm margin remains an alternative to the MidV-based approach for reducing healthy tissue exposure in lung SBRT. Compared to PTVMidV, PTVITV + 3mm significantly reduced the PTV while still maintaining an adequate in-treatment target coverage.

Head-and-Neck MRI-only radiotherapy treatment planning: From acquisition in treatment position to pseudo-CT generation.

PURPOSE: In context of head-and-neck radiotherapy, this study aims to compare MR image quality according to diagnostic (DIAG) and radiotherapy (RT) setups; and to optimise an MRI-protocol (including 3D T1 and T2-weighted sequences) for dose-planning (based on pseudo-CT generation). MATERIALS AND METHODS: To compare DIAG and RT setups, signal-to-noise-ratio (SNR) and percentage-image-uniformity (PIU) were computed on T1 images of phantoms and volunteers. Influence of the sample conductivity on SNR was quantified using homemade phantoms. To obtain reliable T1 and T2 images for RT-planning, an experimental design was performed on volunteers by using SNR, contrast-to-noise-ratio (CNR) and mean-opinion-score (MOS). Further, pseudo-CTs were generated from 8 patients T2 images with a state-of-art deep-learning method. These pseudo-CTs were evaluated by mean-absolute-error (MAE) and mean-error (ME). RESULTS: SNR was higher for DIAG-setup compared to RT-setup (SNR-ratio=1.3). A clear influence of the conductivity on SNR was observed. PIU was higher for DIAG-setup (38.8%) compared to RT-setup (33.5%). Regarding the protocol optimisation, SNR, CNR, and MOS were 20.6, 6.16, and 3.91 for the optimal T1 sequence. For the optimal T2 sequence, SNR, CNR and MOS were 25.6, 44.46 and 4.0. In the whole head-and-neck area, the mean MAE and ME of the pseudo-CTs were 82.8 and -3.9 HU. CONCLUSION: We quantified the image quality decrease induces by using an RT-setup for head-and-neck radiotherapy. To compensate this decrease, an MRI protocol was optimised by using an experimental design. This protocol of 15minutes provides accurate images which could be used for MRI-dose-planning in clinical practice.

Implementation of an optimization method for parotid gland sparing during inverse planning for head and neck cancer radiotherapy.

PURPOSE: To guide parotid gland (PG) sparing at the dose planning step, a specific model based on overlap between PTV and organ at risk (Moore et al.) was developed and evaluated for VMAT in head-and-neck (H&N) cancer radiotherapy. MATERIALS AND METHODS: One hundred and sixty patients treated for locally advanced H&N cancer were included. A model optimization was first performed (20 patients) before a model evaluation (110 patients). Thirty cases were planned with and without the model to quantify the PG dose sparing. The inter-operator variability was evaluated on one case, planned by 12 operators with and without the model. The endpoints were PG mean dose (Dmean), PTV homogeneity and number of monitor units (MU). RESULTS: The PG Dmean predicted by the model was reached in 89% of cases. Using the model significantly reduced the PG Dmean: -6.1±4.3Gy. Plans with the model showed lower PTV dose homogeneity and more MUs (+10.5% on average). For the inter-operator variability, PG dose volume histograms without the optimized model were significantly different compared to those with the model; the Dmean standard deviation for the ipsilateral PG decreased from 2.2Gy to 1.2Gy. For the contralateral PG, this value decreased from 2.9Gy to 0.8Gy. CONCLUSION: During the H&N inverse planning, the optimized model guides to the lowest PG achievable mean dose, allowing a significant PG mean dose reduction of -6.1Gy. Integrating this method at the treatment-planning step significantly reduced the inter-patient and inter-operator variabilities.

Voxel-based identification of local recurrence sub-regions from pre-treatment PET/CT for locally advanced head and neck cancers.

BACKGROUND: Overall, 40% of patients with a locally advanced head and neck cancer (LAHNC) treated by chemoradiotherapy (CRT) present local recurrence within 2 years after the treatment. The aims of this study were to characterize voxel-wise the sub-regions where tumor recurrence appear and to predict their location from pre-treatment 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) images. MATERIALS AND METHODS: Twenty-six patients with local failure after treatment were included in this study. Local recurrence volume was identified by co-registering pre-treatment and recurrent PET/CT images using a customized rigid registration algorithm. A large set of voxel-wise features were extracted from pre-treatment PET to train a random forest model allowing to predict local recurrence at the voxel level. RESULTS: Out of 26 expert-assessed registrations, 15 provided enough accuracy to identify recurrence volumes and were included for further analysis. Recurrence volume represented on average 23% of the initial tumor volume. The MTV with a threshold of 50% of SUVmax plus a 3D margin of 10 mm covered on average 89.8% of the recurrence and 96.9% of the initial tumor. SUV and MTV alone were not sufficient to identify the area of recurrence. Using a random forest model, 15 parameters, combining radiomics and spatial location, were identified, allowing to predict the recurrence sub-regions with a median area under the receiver operating curve of 0.71 (range 0.14-0.91). CONCLUSION: As opposed to regional comparisons which do not bring enough evidence for accurate prediction of recurrence volume, a voxel-wise analysis of FDG-uptake features suggested a potential to predict recurrence with enough accuracy to consider tailoring CRT by dose escalation within likely radioresistant regions.

[Stereotactic body radiation therapy for hepatocellular carcinoma: Results from a retrospective multicentre study]. / Radiothérapie en conditions stéréotaxiques du carcinome hépatocellulaire : résultats d'une étude rétrospective multicentrique.

PURPOSE: The purpose of this paper was to describe local control, overall survival, progression-free survival and toxicity of CyberKnife®-based stereotactic body radiation therapy of hepatocellular carcinoma. MATERIAL AND METHODS: Records of all the patients treated for hepatocellular carcinoma at the Eugene-Marquis cancer centre, Rennes and the Bretonneau hospital, Tours (France), between November 2010 and December 2016, were reviewed. Radiation therapy was performed as a salvage treatment, while awaiting liver transplantation or if no other treatment was possible. RESULTS: One hundred and thirty-six patients were consecutively included in the study. The median follow-up was 13months. Median total dose prescribed, fractionation and overall treatment time were respectively 45Gy, three fractions and 5 days. Overall survival, progression-free survival and local control rates at 1year and 2years were 79.8 % and 63.5 %, 61.3 % and 39.4 %; 94.5 % and 91 %. Two grade 3 acute toxicity events and two grade 4 late toxicity events corresponding to a duodenal ulcer have been reported. Seven patients underwent classic radiation-induced hepatitis and 13 patients showed non-classical radiation-induced hepatitis. Barcelona Clinic Liver Cancer stage, World Health Organisation grade and planning target volume were correlated with overall survival in univariate Cox analysis. CONCLUSION: Stereotactic body radiation therapy is effective and well-tolerated for inoperable hepatocellular carcinoma or as a bridge to liver transplantation. Toxicity is mainly related to cirrhotic background and requires a selection of patients and strict dose constraints.

PET-based prognostic survival model after radiotherapy for head and neck cancer.

PURPOSE: The aims of this multicentre retrospective study of locally advanced head and neck cancer (LAHNC) treated with definitive radiotherapy were to (1) identify positron emission tomography (PET)-18F-fluorodeoxyglucose (18F-FDG) parameters correlated with overall survival (OS) in a training cohort, (2) compute a prognostic model, and (3) externally validate this model in an independent cohort. MATERIALS AND METHODS: A total of 237 consecutive LAHNC patients divided into training (n = 127) and validation cohorts (n = 110) were retrospectively analysed. The following PET parameters were analysed: SUVMax, metabolic tumour volume (MTV), total lesion glycolysis (TLG), and SUVMean for the primary tumour and lymph nodes using a relative SUVMax threshold or an absolute SUV threshold. Cox analyses were performed on OS in the training cohort. The c-index was used to identify the highly prognostic parameters. A prognostic model was subsequently identified, and a nomogram was generated. The model was externally tested in the validation cohort. RESULTS: In univariate analysis, the significant PET parameters for the primary tumour included MTV (relative thresholds from 6 to 83% and absolute thresholds from 1.5 to 6.5) and TLG (relative thresholds from 1 to 82% and absolute thresholds from 0.5 to 4.5). For the lymph nodes, the significant parameters included MTV and TLG regardless of the threshold value. In multivariate analysis, tumour site, p16 status, MTV35% of the primary tumour, and MTV44% of the lymph nodes were independent predictors of OS. Based on these four parameters, a prognostic model was identified with a c-index of 0.72. The corresponding nomogram was generated. This prognostic model was externally validated, achieving a c-index of 0.66. CONCLUSIONS: A prognostic model of OS based on primary tumour and lymph node MTV, tumour site, and p16 status was proposed and validated. The corresponding nomogram may be used to tailor individualized treatment.

A density assignment method for dose monitoring in head-and-neck radiotherapy.

BACKGROUND AND PURPOSE: During head-and-neck (H&N) radiotherapy, the parotid glands (PGs) may be overdosed; thus, a tool is required to monitor the delivered dose. This study aimed to assess the dose accuracy of a patient-specific density assignment method (DAM) for dose calculation to monitor the dose to PGs during treatment. PATIENTS AND METHODS: Forty patients with H&N cancer received an intensity modulated radiation therapy (IMRT), among whom 15 had weekly CTs. Dose distributions were calculated either on the CTs (CTref), on one-class CTs (1C-CT, water), or on three-class CTs (3C-CT, water-air-bone). The inter- and intra-patient DAM uncertainties were evaluated by the difference between doses calculated on CTref and 1C-CTs or 3C-CTs. PG mean dose (Dmean) and spinal cord maximum dose (D2%) were considered. The cumulated dose to the PGs was estimated by the mean Dmean of the weekly CTs. RESULTS: The mean (maximum) inter-patient DAM dose uncertainties for the PGs (in cGy) were 23 (75) using 1C-CTs and 12 (50) using 3C-CTs (p ≤ 0.001). For the spinal cord, these uncertainties were 118 (245) and 15 (67; p ≤ 0.001). The mean (maximum) DAM dose uncertainty between cumulated doses calculated on CTs and 3C-CTs was 7 cGy (45 cGy) for the PGs. Considering the difference between the planned and cumulated doses, 53% of the ipsilateral and 80% of the contralateral PGs were overdosed by +3.6 Gy (up to 8.2 Gy) and +1.9 Gy (up to 5.2 Gy), respectively. CONCLUSION: The uncertainty of the three-class DAM appears to be clinically non-significant (<0.5 Gy) compared with the PG overdose (up to 8.2 Gy). This DAM could therefore be used to monitor PG doses and trigger replanning.

Adaptive radiotherapy for head and neck cancer.

INTRODUCTION: Large anatomical variations can be observed during the treatment course intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC), leading to potential dose variations. Adaptive radiotherapy (ART) uses one or several replanning sessions to correct these variations and thus optimize the delivered dose distribution to the daily anatomy of the patient. This review, which is focused on ART in the HNC, aims to identify the various strategies of ART and to estimate the dosimetric and clinical benefits of these strategies. MATERIAL AND METHODS: We performed an electronic search of articles published in PubMed/MEDLINE and Science Direct from January 2005 to December 2016. Among a total of 134 articles assessed for eligibility, 29 articles were ultimately retained for the review. Eighteen studies evaluated dosimetric variations without ART, and 11 studies reported the benefits of ART. RESULTS: Eight in silico studies tested a number of replanning sessions, ranging from 1 to 6, aiming primarily to reduce the dose to the parotid glands. The optimal timing for replanning appears to be early during the first two weeks of treatment. Compared to standard IMRT, ART decreases the mean dose to the parotid gland from 0.6 to 6 Gy and the maximum dose to the spinal cord from 0.1 to 4 Gy while improving target coverage and homogeneity in most studies. Only five studies reported the clinical results of ART, and three of those studies included a non-randomized comparison with standard IMRT. These studies suggest a benefit of ART in regard to decreasing xerostomia, increasing quality of life, and increasing local control. Patients with the largest early anatomical and dose variations are the best candidates for ART. CONCLUSION: ART may decrease toxicity and improve local control for locally advanced HNC. However, randomized trials are necessary to demonstrate the benefit of ART before using the technique in routine practice.

[Dose constraints to organs at risk for conformational and stereotactic radiotherapy: Small bowel and duodenum]. / Contraintes de doses aux organes à risque en radiothérapie conformationnelle et stéréotaxique : intestin grêle et duodénum.

Radiotherapy of abdominopelvic primary or secondary lesions in conformational or stereotactic techniques is in full development. The small bowel is highly sensitive to irradiation and is the main organ at risk limiting prescription doses. This literature review aims to define the dose constraints to the small bowel and the duodenum in conformational and stereotactic body radiotherapy. The small bowel including the duodenum, jejunum and ileum is delineated on the simulation scanner. The radio-induced intestinal toxicities are acute related to the cellular depopulation of the intestinal mucosa, and late of more complex pathophysiology associating depletion in stem cells, microangiopathy, chronic inflammation and fibrosis. The main predictive factor of intestinal toxicity is the dose-volume ratio. In conformational radiotherapy, the dose constraints to the duodenum are: V25Gy<45% and V35Gy<20%. The jejunum and ileum dose constraints are for delineation by intestinal loop or peritoneal cavity respectively: V15Gy<275mL or V15Gy<830mL and V45Gy<150mL. In stereotactic body radiotherapy, small bowel dose constraints depend on fractionation and are defined on a small volume and on a maximum dose at one point. Intestinal toxicity is also dependent on factors intrinsic to the patient and radiosensitizers such as targeted therapies or chemotherapies. With the development of new techniques allowing dose escalation on the tumour and the development of inverse planning, the definition of dose constraints to the small bowel is essential for current practice.

A PET-based nomogram for oropharyngeal cancers.

PURPOSE: In the context of locally advanced oropharyngeal cancer (LAOC) treated with definitive radiotherapy (RT) (combined with chemotherapy or cetuximab), the aims of this study were: (1) to identify PET-FDG parameters correlated with overall survival (OS) from a first cohort of patients; then (2) to compute a prognostic score; and (3) finally to validate this scoring system in a second independent cohort of patients. MATERIALS AND METHODS: A total of 76 consecutive patients (training cohort from Rennes) treated with chemoradiotherapy or RT with cetuximab for LAOC were used to build a predictive model of locoregional control (LRC) and OS based on PET-FDG parameters. After internal calibration and validation of this model, a nomogram and a scoring system were developed and tested in a validation cohort of 46 consecutive patients treated with definitive RT for LAOC in Lausanne. RESULTS: In multivariate analysis, the metabolic tumour volume (MTV) of the primary tumour and the lymph nodes were independent predictive factors for LRC and OS. Internal calibration showed a very good adjustment between the predicted OS and the observed OS at 24 months. Using the predictive score, two risk groups were identified (median OS 42 versus 14 months, p < 0.001) and confirmed in the validation cohort from Lausanne (median OS not reached versus 26 months, p=0.008). CONCLUSIONS: This is the first report of a PET-based nomogram in oropharyngeal cancer. Interestingly, it appeared stronger than the classical prognostic factors and was validated in independent cohorts markedly diverging in many aspects, which suggest that the observed signal was robust.

A Nomogram to predict parotid gland overdose in head and neck IMRT.

PURPOSES: To generate a nomogram to predict parotid gland (PG) overdose and to quantify the dosimetric benefit of weekly replanning based on its findings, in the context of intensity-modulated radiotherapy (IMRT) for locally-advanced head and neck carcinoma (LAHNC). MATERIAL AND METHODS: Twenty LAHNC patients treated with radical IMRT underwent weekly computed tomography (CT) scans during IMRT. The cumulated PG dose was estimated by elastic registration. Early predictors of PG overdose (cumulated minus planned doses) were identified, enabling a nomogram to be generated from a linear regression model. Its performance was evaluated using a leave-one-out method. The benefit of weekly replanning was then estimated for the nomogram-identified PG overdose patients. RESULTS: Clinical target volume 70 (CTV70) and the mean PG dose calculated from the planning and first weekly CTs were early predictors of PG overdose, enabling a nomogram to be generated. A mean PG overdose of 2.5Gy was calculated for 16 patients, 14 identified by the nomogram. All patients with PG overdoses >1.5Gy were identified. Compared to the cumulated delivered dose, weekly replanning of these 14 targeted patients enabled a 3.3Gy decrease in the mean PG dose. CONCLUSION: Based on the planning and first week CTs, our nomogram allowed the identification of all patients with PG overdoses >2.5Gy to be identified, who then benefitted from a final 4Gy decrease in mean PG overdose by means of weekly replanning.

Toxicity and efficacy of cetuximab associated with several modalities of IMRT for locally advanced head and neck cancer.

PURPOSE: Intensity-modulated radiation therapy (IMRT) has shown its interest for head and neck cancer treatment. In parallel, cetuximab has demonstrated its superiority against exclusive radiotherapy. The objective of this study was to assess the acute toxicity, local control and overall survival of cetuximab associated with different IMRT modalities compared to platinum-based chemotherapy and IMRT in the ARTORL study (NCT02024035). PATIENTS AND METHOD: This prospective, multicenter study included patients with epidermoid or undifferentiated nasopharyngeal carcinoma, epidermoid carcinoma of oropharynx and oral cavity (T1-T4, M0, N0-N3). Acute toxicity, local control and overall survival were compared between groups (patients receiving cetuximab or not). Propensity score analysis at the ratio 1:1 was undertaken in an effort to adjust for potential bias between groups due to non-randomization. RESULTS: From the 180 patients included in the ARTORL study, 29 patients receiving cetuximab and 29 patients treated without cetuximab were matched for the analysis. Ten patients (34.5%) reported acute dermal toxicity of grade 3 in the cetuximab group versus three (10.3%) in the non-cetuximab group obtained after matching (P=0.0275). Cetuximab was not significantly associated with more grade 3 mucositis (P=0.2563). There were no significant differences in cutaneous or oral toxicity for patients treated with cetuximab between the different IMRT modalities (P=1.000 and P=0.5731, respectively). There was no significant difference in local relapse-free survival (P=0.0920) or overall survival (P=0.4575) between patients treated with or without cetuximab. CONCLUSION: Patients treated with cetuximab had more cutaneous toxicities, but oral toxicity was similar between groups. The different IMRT modalities did not induce different toxicity profiles.

[Image-guided and adaptive radiotherapy]. / Radiothérapie guidée par l'image et adaptative.

Image-guided radiotherapy (IGRT) aims to take into account anatomical variations occurring during irradiation by visualization of anatomical structures. It may consist of a rigid registration of the tumour by moving the patient, in case of prostatic irradiation for example. IGRT associated with intensity-modulated radiotherapy (IMRT) is strongly recommended when high-dose is delivered in the prostate, where it seems to reduce rectal and bladder toxicity. In case of significant anatomical deformations, as in head and neck tumours (tumour shrinking and decrease in volume of the salivary glands), replanning appears to be necessary, corresponding to the adaptive radiotherapy. This should ideally be "monitored" and possibly triggered based on a calculation of cumulative dose, session after session, compared to the initial planning dose, corresponding to the concept of dose-guided adaptive radiotherapy. The creation of "planning libraries" based on predictable organ positions (as in cervical cancer) is another way of adaptive radiotherapy. All of these strategies still appear very complex and expensive and therefore require stringent validation before being routinely applied.

[Mid-ventilation position planning: optimal model for dose distribution in lung tumour]. / Planification selon la position moyenne du cycle respiratoire : modèle de planification optimale pour une distribution de dose dans les tumeurs pulmonaires.

PURPOSE: The dose distribution for lung tumour is estimated using a 3D-CT scan, and since a person breathes while the images are captured, the dose distribution doesn't reflect the reality. A 4D-CT scan integrates the motion of the tumour during breathing and, therefore, provides us with important information regarding tumour's motion in all directions, the motion volume (ITV) and the time-weighted average position (MVP). PATIENT AND METHODS: Based on these two concepts, we have estimated, for a lung carcinoma case a 3D dose distribution from a 3D-CT scan, and a 4D dose distribution from a 4-D CT scan. To this, we have applied a non-rigid registration to estimate the cumulative dose. RESULTS: Our study shows that the 4D dose estimation of the GTV is almost the same when made using MVP and ITV concepts, but sparring of the healthy lung is better done using the MPV model (MVP), as compared to the ITV model. This improvement of the therapeutic index allows, from a projection on the theoretical maximal dose to PTV (strictly restricted to doses for the lungs and the spinal cord), for an increase of about 11% on the total dose (maximal dose of 86 Gy for the ITV and 96 Gy for the MVP). CONCLUSION: Further studies with more patients are needed to confirm our data.

[From image-guided radiotherapy to dose-guided radiotherapy]. / De la radiothérapie guidée par l'image à la radiothérapie guidée par la dose.

PURPOSE: In case of tumour displacement, image-guided radiotherapy (IGRT) based on the use of cone beam CT (tomographie conique) allows replacing the tumour under the accelerator by rigid registration. Anatomical deformations require however replanning, involving an estimation of the cumulative dose, session after session. This is the objective of this study. PATIENTS AND METHODS: Two examples of arc-intensity modulated radiotherapy are presented: a case of prostate cancer (total dose=80 Gy) with tomographie conique (daily prostate registration) and one head and neck cancer (70 Gy). For the head and neck cancer, the patient had a weekly scanner allowing a dose distribution calculation. The cumulative dose was calculated per voxel on the planning CT after deformation of the dose distribution (with trilinear interpolation) following the transformation given by a non-rigid registration step (Demons registration method) from: either the tomographie conique (prostate), or the weekly CT. The cumulative dose was eventually compared with the planned dose. RESULTS: In cases of prostate irradiation, the "cumulative" dose corresponded to the planned dose to the prostate. At the last week of irradiation, it was above the planned dose for the rectum and bladder. The volume of rectal wall receiving more than 50 Gy (V50) was 20% at the planning and 26% at the end of treatment, increasing the risk of rectal toxicity (NTCP) of 14%. For the bladder wall, V50 were 73% and 82%, respectively. In head and neck, the "cumulative" dose to the parotid exceeded the planned dose (mean dose increasing from 46 Gy to 54 Gy) from the 5th week of irradiation on, suggesting the need for replanning within the first 5 weeks of radiotherapy. CONCLUSION: The deformable registration estimates the cumulative dose delivered in the different anatomical structures. Validation on digital and physical phantoms is however required before clinical evaluation.

[Which IMRT? From "step and shoot" to VMAT: physicist point of view]. / Quelle RCMI? Du step and shoot au VMAT: point de vue du physicien.

Intensity-modulated radiation therapy (IMRT) is essential to have a dose distribution matching with the planning target volume (PTV) in case of concave-shape target. Today IMRT delivery techniques with linear accelerator can be divided into two classes: techniques with fixed gantry, called "step and shoot" (S&S) and "sliding window" (SW), and rotational techniques, called intensity modulated arc therapy (IMAT) and volumetric modulated arc therapy (VMAT). We discuss about constraints for IMRT implementation from dosimetric planning to treatment delivery. We compare S&S and VMAT performances concerning dose distribution quality, efficiency and delivery time. We describe quality controls that must be implemented and the methods for analysis and follow-up performances. VMAT tends to yield similar dose distribution to MRT with fixed gantry. VMAT also decreases monitor units as well as treatment delivery time to less than 5 minutes. However, VMAT is an IMRT technique more difficult to master than S&S technique because there are more variable parameters.