Effect of conventional and ultra-high dose rate "FLASH" irradiations on preclinical tumour models: A systematic analysis: Tumour response to CONV and UHDR irradiation.

When compared to conventional dose rate irradiation (CONV), ultra-high dose rate irradiation (UHDR) has shown superior normal tissue sparing. However, a clinically relevant widening of the therapeutic window by UHDR, termed "FLASH effect", also depends on the tumour toxicity obtained by UHDR. Based on a combined analysis of published literature, the current study re-examines the hypothesis of tumour isoefficacy for UHDR versus CONV and aims to identify potential knowledge gaps to inspire future in vivo studies. A systematic literature search identified publications assessing in vivo tumour responses comparing UHDR and CONV. Qualitative and quantitative analyses were performed, including combined analyses of tumour growth and survival data. We identified 66 data sets from 15 publications that compared UHDR and CONV for tumour efficacy. The median number of animals per group was 9 (range: 3-15) and the median follow-up period was 30.5 (range: 11-230) days after the first irradiation. Tumour growth assays were the predominant model used. Combined statistical analyses of tumour growth and survival data are consistent with UHDR isoefficacy compared to CONV. Only one study determined tumour-controlling dose (TCD <sub>50</sub> ) and reported statistically non-significant differences. The combined quantitative analyses of tumour responses support the assumption of UHDR isoefficacy compared to CONV. However, the comparisons are primarily based on heterogeneous tumour growth assays with limited numbers of animals and short follow-up, and most studies do not assess long-term tumour control probability. Therefore, the assays may be insensitive in resolving smaller response differences, such as responses of radio-resistant tumour sub-clones. Hence, tumour cure experiments, including additional TCD <sub>50</sub> experiments, are needed to confirm the assumption of isoeffectiveness in curative settings

Cancer de l'oesophage : quel standard de traitement pour quel patient?

Le traitement optimal des patients atteints de cancers de l'oesophage et de la Jonction oeso-gastrique est assuré par une prise en charge multidisciplinaire. L'étape fondamentale du bilan préopératoire Inclut non seulement le staging, mais aussi l'évaluation des comorbidités qui conditionneront l'approche médicale, chirurgicale ou combinée. Une résection chirurgicale complète (R0) est à même d'assurer une survie globale à cinq ans de 20 à 30%. Le pronostic est peu modifié dans les nombreuses études de traitements adjuvants et néoadjuvants, difficilement comparables entre elles en raison de l'hétérogénéité des collectifs, des traitements chirurgicaux et oncologiques

Current landscape of palliative radiotherapy for non-small-cell lung cancer.

Radiotherapy (RT) is a cornerstone in the management of advanced stage III and stage IV non-small-cell lung cancer (NSCLC) patients. Despite international guidelines, clinical practice remains heterogeneous. Additionally, the advent of stereotactic ablative RT (SABR) and new systemic treatments such as immunotherapy have shaken up dogmas in the approach of these patients. This review will focus on palliative thoracic RT for NSCLC but will also discuss the role of stereotactic radiotherapy, endobronchial brachytherapy (EBB), the interest of concomitant treatments (chemotherapy and immunotherapy), and the role of RT in lung cancer emergencies with palliative intent

Improvement of saliva production in ENT cancer patients treated by IMRT

Intensity modulated radiotherapy (IMRT) is a conformal radiotherapy that produces concave and irregular target volume dose distributions. IMRT has a potential to reduce the volume of healthy tissue irradiated to a high dose, but this often at the price of an increased volume of normal tissue irradiated to a low dose. Clinical benefits of IMRT are expected to be most pronounced at the body sites where sensitive normal tissues surround or are located next to a target with a complex 3D shape. The irradiation doses needed for tumor control are often markedly higher than the tolerance of the radiation sensitive structures such as the spinal cord, the optic nerves, the eyes, or the salivary glands in the treatment of head and neck cancer. Parotid gland salivary flow is markedly reduced following a cumulative dose of 30 50 Gy given with conventional fractionation and xerostomia may be prevented in most patients using a conformal parotid-sparing radiotherapy technique. However, in cohort studies where IMRT was compared with conventional and conformal radiotherapy techniques in the treatment of laryngeal or oropharyngeal carcinoma, the dosimetric advantage of IMRT translated into a reduction of late salivary toxicity with no apparent adverse impact on the tumor control. IMRT might reduce the radiation dose to the major salivary glands and the risk of permanent xerostomia without compromizing the likelihood for cure. Alternatively, IMRT might allow the target dose escalation at a given level of normal tissue damage. We describe here the clinical results on postirradiation salivary gland function in head and neck cancer patients treated with IMRT, and the technical aspects of IMRT applied. The results suggest that the major salivary gland function can be maintained with IMRT without a need to compromise the clinical target volume dose, or the locoregional control

Vertebral compression fracture during stereotactic body radiotherapy for spinal metastasis: A rare case of tracking failure.

Spinal metastasis are a daily challenge in clinical practice. Stereotactic body radiotherapy (SBRT) allows delivery of definitive treatment with excellent long-term control rates. Its implementation needs dedicated devices and day-to-day image-guided radiotherapy (IGRT). The XSight™ spine tracking system, integrates with the CyberKnife® (Accuray™), provides a fiducial-free tracking system for spinal SBRT. We report a rare case of tracking failure during treatment due to the occurrence of a vertebral compression fracture (VCF)

The Effect of Amifostine on Acute and Late Radiation Side Effects in Head and Neck Cancer Patients

Objective: We aimed to investigate the effect of amifostine on acute and late side effects, and its tolerability in head and neck cancer patients treated with radiotherapy (RT). Material and Methods: The study included 87 patients with primary head and neck cancers and cervical lymph node metastases from unknown primary cancers treated with RT alone or combined with chemotherapy (CT). Forty-one patients (47%) received amifostine combined with RT (ART group) and 46 patients (52%) received RT without amifostine (RT group). The patients were evaluated every week during the treatment and at month 1 and 2 after the completion of RT for acute side effects and month 3, 6, 9, 12, and 24 after the treatment for late side effects according to SOMA/LENT scale. Amifostine was administered prior to RT, along with anti-emetic prophylaxis. The two groups were compared with the Student's t and Mann-Whitney U and Chi-square tests. Results: The ART group had significantly less toxicity (grade! 1 mucositis, grade 2 fibrosis) than patients in the RT group (p=0.001, p=0.03, respectively). At week 3 of RT grade 2 mucositis developed in two patients (5%) in the ART group and 10 patients (22%) in the RT group (p=0.02). The protective effect of amifostine on skin reactions developed at week 4 of RT (p=0.05). Grade 3 xerostomia at 9, 12, and 15 months of follow-up (p=0.02, p=0.02, and p=0.02, respectively), grade 2 xerostomia at 18 and 24 months (p=0.02 and p=0.01, respectively) and fibrosis at 15, 18 and 24 months (p=0.05, p=0.02 and p=0.02, respectively) decreased markedly in the ART group compared with the RT group. Emesis was the most common adverse effect of amifostine. Conclusion: Daily administration of amifostine during RT was effective in avoiding late grade 2-3 xerostomia, as well as grade 2 fibrosis

Fiducial markers for stereotactic lung radiation therapy: review of the transthoracic, endovascular and endobronchial approaches.

Stereotactic body radiation therapy is an alternative to surgery for early-stage, inoperable peripheral non-small cell lung cancer. As opposed to linear accelerator (linac)-based (e.g. gating) and free-breathing techniques, CyberKnife® with Synchrony® technology allows accurate radiation delivery by means of a real-time respiratory motion tracking system using, in most cases, metal fiducial markers (FMs) placed in the vicinity of the target. The aims of this review are as follows. First, to describe the safety and efficacy of the transthoracic, endovascular and endobronchial FM insertion techniques for peripheral pulmonary lesions (PPLs). Second, to analyse performance in terms of the migration and tracking rates of different FM types. Recent developments in FM tracking for central lesions will also be reviewed. In conclusion, for PPLs, the endobronchial approach provides a low rate of pneumothorax, offers the possibility of concurrent diagnostic sampling for both the PPL and the lymph nodes, and, finally, reduces the intervention time compared to other techniques. In this context, coil-tailed and coil-spring FMs have shown the lowest migration rate with a consequently high tracking rate

Total-body irradiation using linac-based volumetric modulated arc therapy: Its clinical accuracy, feasibility and reliability.

To report the feasibility, accuracy, and reliability of volumetric modulated arc therapy (VMAT)-based total-body irradiation (TBI) treatment in patients with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). From 2015 to 2018, 30 patients with AML or ALL were planned and treated with VMAT-based TBI, which consisted of three isocenters and three overlapping arcs. TBI dose was prescribed to 90% of the planning treatment volume (PTV) receiving 12 Gy in six fractions, at two fractions per day. Mean lung and kidney doses were restricted less than 10 Gy, and maximum lens dose less than 6 Gy. Quality assurance (QA) comprised the verification of the irradiation plans via dose-volume histogram (DVH) based 3D patient QA system. Average mean lung dose was 9.7 ± 0.2 Gy, mean kidney dose 9.6 ± 0.2 Gy, maximum lens dose 4.5 ± 0.4 Gy, mean PTV dose 12.7 ± 0.1 Gy, and heterogeneity index of PTV was 1.16 ± 0.02 in all patients. Grade 3 or more acute radiation toxicity was not observed. When comparing plan and DVH-based 3D patient QA results, average differences of 3.3% ± 1.3 in mean kidney doses, 1.1% ± 0.7 in mean lung doses, and 0.9% ± 0.4 in mean target doses were observed. Linac-based VMAT increased the dose homogeneity of TBI treatment more than extended SSD techniques. Partial cone-beam CT and optical surface-guided system assure patient positioning. DVH-based 3D patient dose verification QA was possible with linac-based VMAT showing small differences between planned and delivered doses. It is feasible, accurate, and reliable