Total body irradiation using helical tomotherapy: Set-up experience and in-vivo dosimetric evaluation.

PURPOSE: Helical Tomotherapy (HT) appears as a valuable technique for total body irradiation (TBI) to create highly homogeneous and conformal dose distributions with more precise repositioning than conventional TBI techniques. The aim of this work is to describe the technique implementation, including treatment preparation, planning and dosimetric monitoring of TBI delivered in our institution from October 2016 to March 2019. MATERIAL AND METHOD: Prior to patient care, irradiation protocol was set up using physical phantoms. Gafchromic films were used to assess dose distribution homogeneity and evaluate imprecise patient positioning impact. Sixteen patients' irradiations with a prescribed dose of 12Gy were delivered in 6 fractions of 2Gy over 3 days. Pre-treatment quality assurance (QA) was performed for the verification of dose distributions at selected positions. In addition, in-vivo dosimetry was carried out using optically stimulated luminescence dosimeters (OSLD). RESULTS: Planning evaluation, as well as results of pre-treatment verifications, are presented. In-vivo dosimetry showed the strong consistency of OSLD measured doses. OSLD mean relative dose differences between measurement and calculation were respectively +0,96% and -2% for armpit and hands locations, suggesting better reliability for armpit OSLD positioning. Repercussion of both longitudinal and transversal positioning inaccuracies on phantoms is depicted up to 2cm shifts. CONCLUSION: The full methodology to set up TBI protocol, as well as dosimetric evaluation and pre-treatment QA, were presented. Our investigations reveal strong correspondence between planned and delivered doses shedding light on the dose reliability of OSLD for HT based TBI in-vivo dosimetry.

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.

[Radiation-oncology horizon 2030: From microbiota to plasma laser]. / Oncologie-radiothérapie horizon 2030 : du microbiote au laser plasma.

Advances in physical, technological and biological fields have made radiation oncology a discipline in continual evolution. New current research areas could be implemented in the clinic in the near future. In this review in the form of several interviews, various promising themes for our specialty are described such as the gut microbiota, tumor organoids (or avatar), artificial intelligence, connected therapies, nanotechnologies and plasma laser. The individual prediction of the best therapeutic index combined with the integration of new technologies will ideally allow highly personalized treatment of patients receiving radiation therapy.

[Use of nanoparticles as radiosensitizing agents in radiotherapy: State of play]. / Utilisation de nanoparticules comme agent radiosensibilisant en radiothérapie : où en est-on ?

Nanomedicine has undergone significant development since the 2000s and it is only very recently that two metallic nanoparticles have emerged in clinical trials. The mechanism of these radiosensitizing agents is based on the presence of atoms with a high atomic number (Z) allowing a higher dose deposition into the tumor during irradiation. The first nanoparticle used in humans is NBTXR3, composed of hafnium (Z=79), with intratumor injection for the treatment of sarcoma. Another gadolinium-based nanoparticle (Z=64), AGuIX, has been used for intravenous injection in the treatment of brain metastases. The preliminary results are promising in terms of feasibility, safety and efficacy, as evidenced by the significant number of ongoing clinical trials. The upcoming challenges for the development of nanoparticles will be the targeting of cancer cells, their biodistribution into the body, their eventual toxicity and their industrial production. In the coming years, modalities of administration and optimal combinations with radiotherapy should be defined in connection with fundamental research.

Significant dose reduction using synchrotron radiation computed tomography: first clinical case and application to high resolution CT exams.

Since the invention of Computed Tomography (CT), many technological advances emerged to improve the image sensitivity and resolution. However, no new source types were developed for clinical use. In this study, for the first time, coherent monochromatic X-rays from a synchrotron radiation source were used to acquire 3D CTs on patients. The aim of this work was to evaluate the clinical potential of the images acquired using Synchrotron Radiation CT (SRCT). SRCTs were acquired using monochromatic X-rays tuned at 80 keV (0.350 × 0.350 × 2 mm3 voxel size). A quantitative image quality comparison study was carried out on phantoms between a state of the art clinical CT and SRCT images. Dedicated iterative algorithms were developed to optimize the image quality and further reduce the delivered dose by a factor of 12 while keeping a better image quality than the one obtained with a clinical CT scanner. We finally show in this paper the very first SRCT results of one patient who received Synchrotron Radiotherapy in an ongoing clinical trial. This demonstrates the potential of the technique in terms of image quality improvement at a reduced radiation dose for inner ear visualization.

Pre- and postoperative radiotherapy for extremity soft tissue sarcoma: Evaluation of inter-observer target volume contouring variability among French sarcoma group radiation oncologists.

PURPOSE: The purpose of this study was to evaluate, during a national workshop, the inter-observer variability in target volume delineation for primary extremity soft tissue sarcoma radiation therapy. METHODS AND MATERIALS: Six expert sarcoma radiation oncologists (members of French Sarcoma Group) received two extremity soft tissue sarcoma radiation therapy cases 1: one preoperative and one postoperative. They were distributed with instructions for contouring gross tumour volume or reconstructed gross tumour volume, clinical target volume and to propose a planning target volume. The preoperative radiation therapy case was a patient with a grade 1 extraskeletal myxoid chondrosarcoma of the thigh. The postoperative case was a patient with a grade 3 pleomorphic undifferentiated sarcoma of the thigh. Contour agreement analysis was performed using kappa statistics. RESULTS: For the preoperative case, contouring agreement regarding GTV, gross tumour volume GTV, clinical target volume and planning target volume were substantial (kappa between 0.68 and 0.77). In the postoperative case, the agreement was only fair for reconstructed gross tumour volume (kappa: 0.38) but moderate for clinical target volume and planning target volume (kappa: 0.42). During the workshop discussion, consensus was reached on most of the contour divergences especially clinical target volume longitudinal extension. The determination of a limited cutaneous cover was also discussed. CONCLUSION: Accurate delineation of target volume appears to be a crucial element to ensure multicenter clinical trial quality assessment, reproducibility and homogeneity in delivering RT. radiation therapy RT. Quality assessment process should be proposed in this setting. We have shown in our study that preoperative radiation therapy of extremity soft tissue sarcoma has less inter-observer contouring variability.

[Biochemical recurrence after curative treatment for localized prostate cancer: Performance of choline PET/CT in the assessment of local recurrence]. / Récidive biochimique après traitement curatif d'un adénocarcinome prostatique localisé: intérêt de la TEP à la choline dans l'évaluation de la récidive locale.

OBJECTIVE: To establish 18 fluorocholine-positron emission tomography/computed tomography (F-PET/CT) performances for the detection of local recurrence in a population of patients with biochemical failure after primary curative treatment for localized prostate carcinoma. MATERIAL AND METHOD: From February 2011 to February 2014, 55 patients underwent a F-PET/CT for biochemical relapse after primary radical therapy for prostate cancer localized or locally advanced. Primary therapies for prostate cancer were 19 radical prostatectomy, 18 radiotherapy, 13 radiotherapy with hormonal treatment, 3 brachytherapy. The median age was 65 years (50-79). The initial staging was 17 T1, 23 T2 and 15 T3, 52 were N0 and N1 3. The median PSA was 12 (3-127). The Gleason score was less than 7, equal to 7 and greater than 7 at 21, 25 and 9 patients respectively. The average time to recurrence was 69.5 months (8-147) with a median PSA of 2.9 ng/mL (0.48-41). RESULTS: In 42 cases, F-PET/CT showed uptake, suggesting a recurrence, metastatic (6), nodal (26) or local isolated (10). The focal uptake in PET commissioned in 5 cases prostate biopsy, confirming the histological recurrence of prostate cancer in 4 cases. Among the 10 patients with isolated local recurrence, 8 underwent salvage radiotherapy. Of the 13 cases where the (F-PET/CT) showed no recurrence, 7 multiparametric MRI were performed. The MRI showed a local recurrence in 3 patients, the diagnoses were confirmed with prostate biopsy for two of them. CONCLUSION: In our study, for the patients with biochemical relapse of prostate adenocarcinoma localized or locally advanced, (F-PET/CT) was able to detect local recurrence isolated in nearly half the cases but did not show sufficient sensitivity to exclude recurrence local if negative. It does not replace MRI or additional prostate biopsy.

Results of a cohort of 200 hormone-naïve consecutive patients with prostate cancer treated with iodine 125 permanent interstitial brachytherapy by the same multidisciplinary team.

PURPOSE: To report survival and morbidity of a cohort of 200 hormone-naïve consecutive patients with localized prostate cancer, treated by low-dose rate brachytherapy within the frame of multidisciplinary approach. PATIENTS AND METHODS: Between 2001 and 2011, 200 patients were treated by the same team with 125 iodine seeds: 167 low-risk and 33 intermediate risk according to the d'Amico classification; eligible patients had clinical stage T1/T2a-b, Gleason score 3+3 or 3+4, baseline prostate-specific antigen level below 15ng/mL, prostate volume less than 60cm(3). The median number of random biopsies was 12 (range 6-32) and the breakdown of positive cores was as follows: 1 (29%), 2 (35%), 3 or more (36%). Acute morbidity was assessed according to the Common Terminology Criteria for Adverse Events and late toxicity according to the EORTC/RTOG scale. Data were prospectively collected. RESULTS: The median follow-up was 69 months (range 16 to 135). The 5- and 10-year biochemical relapse free survivals were 95.6% (95% confidence interval [CI]: 91-98) and 89.7% (95% CI: 79.4-95.0). The 5-year and 10-year overall survival were respectively 96.4% (95% CI: 92-98.4) and 89.7% (95% CI: 80.8-94.6%) and the 10-year disease specific survival, 99.1% (95% CI: 93.0-99.9). The 5- and 10-year grade 3 acute toxicity cumulative rate were respectively 3.3% (95% CI: 1.4-6.6) and 4% (95% CI: 1.4-6.6) and the 5- and 10-year grades 3 cumulative late toxicity 2.5% (95% CI: 2.0-5.9) and 4% (95% CI: 2.0-5.9). CONCLUSION: Brachytherapy managed within the frame of a multidisciplinary approach - from diagnosis to evaluation - may offer optimized results with a reduced late toxicity rate, while remaining opened to dosimetry and technical improvements.

The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy.

A new efficient type of gadolinium-based theranostic agent (AGuIX®) has recently been developed for MRI-guided radiotherapy (RT). These new particles consist of a polysiloxane network surrounded by a number of gadolinium chelates, usually 10. Owing to their small size (<5 nm), AGuIX typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes. For example, although a significant proportion of these particles accumulate in tumours, the remainder is rapidly eliminated by the renal route. In addition, in the absence of irradiation, the nanoparticles are well tolerated even at very high dose (10 times more than the dose used for mouse treatment). AGuIX particles have been proven to act as efficient radiosensitizers in a large variety of experimental in vitro scenarios, including different radioresistant cell lines, irradiation energies and radiation sources (sensitizing enhancement ratio ranging from 1.1 to 2.5). Pre-clinical studies have also demonstrated the impact of these particles on different heterotopic and orthotopic tumours, with both intratumoural or intravenous injection routes. A significant therapeutical effect has been observed in all contexts. Furthermore, MRI monitoring was proven to efficiently aid in determining a RT protocol and assessing tumour evolution following treatment. The usual theoretical models, based on energy attenuation and macroscopic dose enhancement, cannot account for all the results that have been obtained. Only theoretical models, which take into account the Auger electron cascades that occur between the different atoms constituting the particle and the related high radical concentrations in the vicinity of the particle, provide an explanation for the complex cell damage and death observed.

[Combination of external irradiation and androgen suppression for prostate cancer: facts and questions]. / Radiothérapie et hormonothérapie pour le cancer de la prostate: acquis et interrogations.

The combination of radiotherapy and androgen suppression with luteinizing hormone releasing hormone agonist is mainly devoted to locally advanced prostate cancer and intermediate or poor risk localized prostate cancer. They are based on phase III randomized trials which have shown that for locally advanced prostate cancer, a four-month complete androgen blockade initiated two months prior radiotherapy and stopped at the completion of radiotherapy increased overall survival in patients with Gleason scores 2-6, meanwhile, an adjuvant long-term androgen suppression (2.5 to three years) improved significantly the overall survival. Complete androgen blockade with a four to six months duration, combined with external irradiation, enhanced the overall survival in patients with intermediate or poor risk localized prostate cancer.