Recommendations for stereotactic body radiation therapy for spine and non-spine bone metastases. A GETUG (French society of urological radiation oncolgists) consensus using a national two-round modified Delphi survey.

Background and purpose: The relevance of metastasis-directed stereotactic body radiation therapy (SBRT) remains to be demonstrated through phase III trials. Multiple SBRT procedures have been published potentially resulting in a disparity of practices. Therefore, the french society of urological radiation oncolgists (GETUG) recognized the need for joint expert consensus guidelines for metastasis-directed SBRT in order to standardize practice in trials carried out by the group. Materials and methods: After a comprehensive literature review, 97 recommendation statements were created regarding planning and delivery of spine bone (SBM) and non-spine bone metastases (NSBM) SBRT. These statements were then submitted to a national online two-round modified Delphi survey among main GETUG investigators. Consensus was achieved if a statement received ≥ 75 % agreements, a trend to consensus being defined as 65-74 % agreements. Any statement without consensus at round one was re-submitted in round two. Results: Twenty-one out of 29 (72.4%) surveyed experts responded to both rounds. Seventy-five statements achieved consensus at round one leaving 22 statements needing a revote of which 16 achieved consensus and 5 a trend to consensus. The final rate of consensus was 91/97 (93.8%). Statements with no consensus concerned patient selection (3/19), dose and fractionation (1/11), prescription and dose objectives (1/9) and organs at risk delineation (1/15). The voting resulted in the writing of step-by-step consensus guidelines. Conclusion: Consensus guidelines for SBM and NSBM SBRT were agreed upon using a validated modified Delphi approach. These guidelines will be used as per-protocole recommendations in ongoing and further GETUG clinical trials.

Management of oropharyngeal squamous cell carcinoma.

This article reviews the various treatment options, by primary or postoperative external radiotherapy and by brachytherapy for the p16-negative oropharyngeal squamous cell carcinoma. Dose levels, fractionation and association with systemic treatments are presented. The need for neck node dissection post local treatment is discussed, as well as specificities for the management of p16-positive tumours. Guidelines for target volume selection and delineation are thoroughly elaborated. Last, the management by radiotherapy of locoregional recurrences is discussed.

Management and work-up procedures of patients with head and neck malignancies treated by radiation.

Radiotherapy alone or in association with systemic treatment plays a major role in the treatment of head and neck tumours, either as a primary treatment or as a postoperative modality. The management of these tumours is multidisciplinary, requiring particular care at every treatment step. We present the update of the recommendations of the French Society of Radiation Oncology on the radiotherapy of head and neck tumours from the imaging work-up needed for optimal selection of treatment volume, to optimization of the dose distribution and delivery.

Quality assurance of radiotherapy in the ongoing EORTC 1420 "Best of" trial for early stage oropharyngeal, supraglottic and hypopharyngeal carcinoma: results of the benchmark case procedure.

INTRODUCTION: The current phase III EORTC 1420 Best-of trial (NCT02984410) compares the swallowing function after transoral surgery versus intensity modulated radiotherapy (RT) in patients with early-stage carcinoma of the oropharynx, supraglottis and hypopharynx. We report the analysis of the Benchmark Case (BC) procedures before patient recruitment with special attention to dysphagia/aspiration related structures (DARS). MATERIALS AND METHODS: Submitted RT volumes and plans from participating centers were analyzed and compared against the gold-standard expert delineations and dose distributions. Descriptive analysis of protocol deviations was conducted. Mean Sorensen-Dice similarity index (mDSI) and Hausdorff distance (mHD) were applied to evaluate the inter-observer variability (IOV). RESULTS: 65% (23/35) of the institutions needed more than one submission to achieve Quality assurance (RTQA) clearance. OAR volume delineations were the cause for rejection in 53% (40/76) of cases. IOV could be improved in 5 out of 12 OARs by more than 10 mm after resubmission (mHD). Despite this, final IOV for critical OARs in delineation remained significant among DARS by choosing an aleatory threshold of 0.7 (mDSI) and 15 mm (mHD). CONCLUSIONS: This is to our knowledge the largest BC analysis among Head and neck RTQA programs performed in the framework of a prospective trial. Benchmarking identified non-common OARs and target delineations errors as the main source of deviations and IOV could be reduced in a significant number of cases after this process. Due to the substantial resources involved with benchmarking, future benchmark analyses should assess fully the impact on patients' clinical outcome.

Field output factors for small fields: A large multicentre study.

PURPOSE: The determination of output factors in small field dosimetry is a crucial point, especially when implementing stereotactic radiotherapy (SRT). Herein, a working group of the French medical physicist society (SFPM) was created to collect small field output factors. The objective was to gather and disseminate information on small field output factors based on different detectors for various clinical SRT equipment and measurement configurations. METHOD: Participants were surveyed for information about their SRT equipment, including the type of linear particle accelerator (linac), collimator settings, measurement conditions for the output factors and the detectors used. Participants had to report both the ratio of detector readings and the correction factors applied as described in the IAEA TRS-483 code of practice for nominal field sizes smaller or equal to 3 cm. Mean field output factors and their associated standard deviations were calculated when data from at least 3 linacs were available. RESULTS: 23 centres were enrolled in the project. Standard deviations of the mean field output factors were systematically smaller than 1.5% for field sizes larger or equal to 1 cm and reached 5% for the smallest field size (0.5 cm). Deviations with published data were smaller than 2% except for the 0.5 cm circular fixed aperture collimator of the CyberKnife where it reached 3.5%. CONCLUSION: These field output factor values obtained via a large multicentre study can be considered as an external cross verification for any radiotherapy centre starting a SRT program and should help minimize systematic errors when determining small field output factors.

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

PURPOSE: The 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 60Gy delivered with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: All consecutive patients that received a definitive CRT>50Gy 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. RESULTS: A 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 60Gy (54-66) and 48Gy (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 11.4Gy (IC 95%: 4.8-19.8), the median volumes receiving up to 20Gy (V20) and 30Gy (V30) were 13.5% (3.0-46.0) and 4.6% (0.7-19.8) respectively. The mean dose delivered to the heart was 13.9Gy (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%). CONCLUSION: We 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.

Subventricular zone involvement at recurrence is a strong predictive factor of outcome following high grade glioma reirradiation.

We aimed to assess the efficacy of stereotactic irradiation for patients with recurrent high-grade glioma (HGG) and identify predictive factors of progression-free survival (PFS) and overall survival (OS) following reirradiation. We identified 32 patients with recurrent brain HGG who had been treated with either single-dose (stereotactic radiosurgery) or fractionated stereotactic radiotherapy between April 2008 and October 2015. Median follow up was 21.4 months (range 12.9-23.2) and median PFS was and 3.3 months (95% CI [2.3-4.7]), respectively. OS was 90.40% (95% CI [73.09-96.80]) at 6 months and 79.55% (95% CI [59.9-90.29]) at 12 months. Univariate analysis showed that biological effective dose at isocenter ≤ 76 Gy was a poor prognostic factor for both OS (83.33 vs. 100% at 6 months, p = 0.032) and median PFS (2.7 vs. 4.7 months, p = 0.025), as was gross tumor volume (GTV) above 1 cm3 for OS (86.15 vs. 94.12% at 6 months, p = 0.043). Contact with the subventricular zone (SVZ) was also a poor prognostic factor for median PFS (2.3 vs. 4.7 months, p = 0.002). Multivariate analysis showed that SVZ contact remained a poor prognostic factor for PFS (hazard ratio = 3.44, 95% CI [1.21-9.82], p = 0.021). Results suggest that reirradiation is a safe and effective treatment option for recurrent HGG in patients with a good Karnosfsky Performance Scale score, a long progression-free interval since first radiation and limited GTV, and that contact to SVZ is a strong prognostic factor for PFS.

[Acute toxicity of breast cancer irradiation with modulated intensity by tomotherapy®]. / Toxicité aiguë de la tomothérapie des cancers mammaires.

PURPOSE: Helical radiation intensity modulated by tomotherapy improves dose distribution to complex and large volumes. The aim of the study was to assess acute toxicity of this technique during breast cancer irradiation after conserving surgery or mastectomy. PATIENTS AND METHODS: Cutaneous toxicities, lung and oesophageal side effects, and breast lymphedema were retrospectively collected according to the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) in 292 patients treated for a breast cancer by tomotherapy between May 2010 and December 2014. After conservative surgery, the dose administered to breast volume and the tumour bed was respectively 52.2Gy and 63.8Gy in 29 fractions. After mastectomy, the dose was 50Gy in 25 fractions. Univariate and multivariate analyses were performed to highlight risk factors for dermatitis and breast oedema. RESULTS: The rate of dermatitis grade 2 and 3 were 22.9% and 1.7% respectively. In univariate analysis, factors associated with acute radiation dermatitis were breast volume (P=0.002), body mass index (BMI) (P<0.0001), the use of chest compression mask (net) (P=0.005) and the localization of the irradiation (P <0.0001). In multivariate analysis, BMI greater than 25kg/m2 (odds ratio [OR]: 3.61, 95% confidence interval [CI]: [1.93-6.74], P<0.0001), the use of a chest mask (OR 2.01, 95% CI [1.06-3.79] P=0.0328) and irradiation after conservative treatment increase the risk of acute radiation dermatitis (mastectomy: OR 0.64, 95% CI [0.04-0.43]; mastectomy with immediate reconstruction with prosthesis: OR 0.13 95% CI [0.10-0.38] P=0.0003). The incidence of breast oedema grade 2 or above was 19.5%, in univariate analysis, there was a correlation with BMI (P=0.003) and smoking (P=0.009). In multivariate analysis, smoking and BMI greater than 25kg/m2 increased the risk of breast oedema (OR 2.47, respectively [95% CI 1.22-5.01] P=0.012 and OR 2.37 [95% CI 1.22-4.59] P=0.01). The rate of radiation pneumonitis of grade 2 or above was 1.4%. Among the patients, 19.9% had esophagitis grade 1 or 2. CONCLUSION: The helical irradiation intensity modulation tomotherapy is a well-tolerated treatment for breast cancer that reduces the high radiation doses to organs at risk.

Monte Carlo dose calculation in presence of low-density media: Application to lung SBRT treated during DIBH.

PURPOSE: Commercial algorithms used in Radiotherapy include approximations that are generally acceptable. However their limits can be seen when confronted with small fields and low-density media. These conditions exist during the treatment of lung cancers with Stereotactic Body Radiation Therapy (SBRT) achieved with the "Deep Inspiration Breath Hold" (DIBH) technique. A Monte Carlo (MC) model of a linear accelerator was used to assess the performance of two algorithms (Varian Acuros and AAA) in these conditions. This model is validated using phantoms with different densities. Lastly, results for SBRT cases are compared to both Acuros and AAA. METHODS: A Varian TrueBeam linac was modeled using GATE/Geant4 and validated by comparing dose distributions for simple fields to measurements in water and in heterogeneous phantoms composed of PMMA and two types of cork (corresponding to lung densities during free-breathing and DIBH). Experimental measurements are also compared to AAA and Acuros. Finally, results of Acuros/AAA are compared to MC for a clinical case (SBRT during DIBH). RESULTS: Based on 1D gamma index comparisons with measurements in water, the TrueBeam model was validated (>97% of points passed this test). In heterogeneous phantoms, and in particular for small field sizes, very low density (0.12g.cm-3) and at the edge of the field, MC model was still in good agreement with measurements whilst AAA and Acuros showed discrepancies. With the patient CT, similar differences between MC and AAA/Acuros were observed for static fields but disappeared using an SBRT arc field. CONCLUSIONS: Our MC model is validated and limits of commercial algorithms are shown in very low densities.

[Radiotherapy of oropharynx carcinoma]. / Radiothérapie des cancers de l'oropharynx.

Indication, doses, technique of radiotherapy and concomitant chemotherapy for oropharynx carcinoma are presented. The recommendations for delineation of the target volumes and organs at risk are detailed.

[Intensity modulation by inverse planning: preliminary results]. / Modulation d'intensité par planification inverse: résultats préliminaires.

An inverse planning algorithm for determining the intensity of modulated beams that generates conformal radiotherapy dose distributions is presented. This algorithm is based on the mathematical analysis of the singular values decomposition. It is integrated in the DOSIGRAY 3D treatment planning software. The dose is calculated by the separation of the primary and scattered radiation. We presented, for a prostate cancer, the modulated intensity profiles and the optimal dose distribution obtained by the inverse optimization software developed and integrated in the treatment planning system. We obtained a region with high doses which geometrically conforms the target volume and spares the neighboring critical structures. This preliminary study showed the feasibility and the managing of the singular value decomposition to generate conformal dose distribution in a clinical environment.