Salivary gland-sparing other than parotid-sparing in definitive head-and-neck intensity-modulated radiotherapy does not seem to jeopardize local control.

International audienceBACKGROUND: The objective was to analyze locoregional (LR) failure patterns in patients with head-and-neck cancer (HNC) treated using intensity-modulated radiotherapy (IMRT) with whole salivary gland-sparing: parotid (PG), submandibular (SMG), and accessory salivary glands represented by the oral cavity (OC). METHODS: Seventy consecutive patients with Stage I-II (23%) or III/IV (77%) HNC treated by definitive IMRT were included. For all LR failure patients, the FDG-PET and CT scans documenting recurrence were rigidly registered to the initial treatment planning CT. Failure volumes (Vf) were delineated based on clinical, radiological, and histological data. The percentage of Vf covered by 95% of the prescription isodose (Vf-V95) was analyzed. Failures were classified as "in-field" if Vf--V95 >= 95%, "marginal" if 20% < Vf-V95 < 95%, and "out-of-field" if Vf-V95 <=20%. Correlation between Vf-V95 and mean doses (Dmean) in the PG, SMG, and OC was assessed using Spearman's rank-order correlation test. The salivary gland dose impact on the LR recurrence risk was assessed by Cox analysis. RESULTS: The median follow-up was 20 months (6--35). Contralateral and ipsilateral PGs were spared in 98% and 54% of patients, respectively, and contralateral and ipsilateral SMG in 26% and 7%, respectively. The OC was spared to a dose <=40 Gy in 26 patients (37%). The 2-year LR control rate was 76.5%. One recurrence was "marginal", and 12 were "in-field". No recurrence was observed in vicinity of spared structures. Vf-V95 was not significantly correlated with Dmean in PG, SMG, and OC. The LR recurrence risk was not increased by lower Dmean in the salivary glands, but by T (p = 0.04) and N stages (p = 0.03). CONCLUSION: Over 92% of LR failures occurred "in-field" within the high dose region when using IMRT with a whole salivary gland-sparing strategy. Sparing SMG and OC in addition to PG thus appears a safe strategy

The synergistic effect of radiotherapy and immunotherapy: A promising but not simple partnership

International audienceRadiotherapy (RT) is one of the main components in the treatment of cancer. The better understanding of the immune mechanisms associated with tumor establishment and how RT affects inflammation and immunity has led to the development of novel treatment strategies. Several preclinical studies support the use of RT in combination with immunotherapy obtaining better local and systemic tumor control. Current ongoing studies will provide information about the optimal RT approach, but the development of reliable predictors of the response from the preclinical and the early phases of clinical studies is necessary to avoid discarding treatment strategies with significant clinical benefit. This review summarize the current concepts of the synergism between RT and immunotherapy, the molecular effects of RT in the tumor microenvironment, their impact on immune activation and its potential clinical applications in trials exploring this important therapeutic opportunity. Finally, the potential predictors of clinical response are discussed

Simultaneously modulated accelerated radiation therapy reduces severe oesophageal toxicity in concomitant chemoradiotherapy of locally advanced non-small-cell lung cancer

International audienceOBJECTIVE: The aim of this study was to evaluate the potential of simultaneously modulated accelerated radiation therapy (SMART) to reduce the incidence of severe acute oesophagitis in the treatment of unresectable locally advanced non-small-cell lung cancer (LANSCLC). METHODS: 21 patients were treated with SMART and concomitant platinum-based chemotherapy. The prescribed doses were limited to 54 Gy at 1.8 Gy per day to the zones of presumed microscopic extent while simultaneously maintaining doses of 66 Gy at 2.2 Gy per day to the macroscopic disease. The whole treatment was delivered over 30 fractions and 6 weeks. Dosimetric parameters of SMART and the standard technique of irradiation [intensity-modulated radiation therapy (IMRT)] were compared. Acute toxicity was prospectively recorded. RESULTS: The highest grade of oesophagitis was 62% (13 patients) grade 1, 33% (7 patients) grade 2 and 5% (1 patient) grade 3. Three (14%) patients experienced acute grade 2 pneumonitis. There was no grade 4 oesophageal or pulmonary toxicity. Doses to the organs at risk were significantly reduced in SMART compared with IMRT [oesophagus: V50Gy, 28.5 Gy vs 39.9 Gy (p = 0.003); V60Gy, 7.1 Gy vs 30.7 Gy (p = 0.003); lung: V20Gy, 27.4 Gy vs 30.1 Gy (p = 0,002); heart: V40Gy, 7.3 Gy vs 10.7 Gy (p = 0.006); spine: Dmax, 42.4 Gy vs 46.4 Gy (p = 0.003)]. With a median follow-up of 18 months (6-33 months), the 1-year local control rate was 70% and the disease-free survival rate was 47%. CONCLUSION: SMART reduces the incidence of severe oesophagitis and improves the whole dosimetric predictors of toxicity for the lung, heart and spine. ADVANCES IN KNOWLEDGE: Our study shows that SMART optimizes the therapeutic ratio in the treatment of LANSCLC, opening a window for dose intensificatio

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

International audienceImage-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

: Quelle RCMI ? Point de vue du physicien.

International audienceIntensity-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

[From image-guided radiotherapy to dose-guided radiotherapy].

International audiencePURPOSE: 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

Optimized radiotherapy to improve clinical outcomes for locally advanced lung cancer

Abstract Background We aimed to evaluate the toxicity, loco-regional control (LRC) and overall survival (OS) associated with accelerated intensity-modulated radiotherapy (IMRT) for locally advanced lung cancer. Methods Seventy-three patients were consecutively treated with IMRT from November 2011 to August 2016. A total dose of 66 Gy was delivered using two different schedules of radiotherapy: simultaneous modulated accelerated radiotherapy (SMART) (30 × 2.2 Gy, across 6 weeks) with or without chemotherapy, or moderate hypofractionated radiotherapy (HRT) (24 × 2.75 Gy, across 4 weeks) in patients unfit to receive concomitant chemotherapy. Data on esophageal and pulmonary toxicities, LRC and OS were prospectively collected. Results The median follow-up duration was 44 months. Severe pneumonitis and esophagitis (grade 3–4) were observed in 7% and 1% of patients respectively, with only one case of grade 4 (pneumonitis). Overall, the 1-year and 2-year LRCs were 76% [95 confidence interval (CI)%: 66–87%] and 62% [95 CI%: 49–77%] respectively. The 1 and 2-year OS rates were 72% [95% CI: 63–83%] and 54% [95 CI%: 43–68%] respectively. None parameters were correlated with LRC or OS. In particular, no difference was observed between patients treated with SMART and H-RT (p = 0.26 and 0.6 respectively), with a 1-year LRC of 74% [95 CI%: 62–86%] for SMART and 91% [95 CI%: 74–100%] for H-RT. No significant differences were observed in the toxicity rates associated with each of the RT schedules. Conclusions Accelerated IMRT for locally advanced lung cancer is associated with low toxicities and high LRC. Moderate hypofractionated RT, by decreasing the total treatment time, may be promising in improving clinical outcomes