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Abstract: Background and purpose: Weight loss, tumor shrinkage, and tissue edema induce substantial modification of patient’s anatomy during head and neck (HN) radiotherapy (RT) or chemo-radiotherapy. These modifications may impact on the dose distribution to both target volumes (TVs) and organs at risk (OARs). Adaptive radiotherapy (ART) where patients are re-imaged and re-planned several times during the treatment is a possible strategy to improve treatment delivery. It however requires the use of specific deformable registration (DR) algorithms that requires proper validation on a clinical material. Materials and methods: Twelve voxel-based DR strategies were compared with a dataset of 5 patients imaged with computed tomography (CT) before and once during RT (on average after a mean dose of 36.8Gy): level-set (LS), level-set implemented in multi-resolution (LSMR), Demons’ algorithm implemented in multi-resolution (DMR), DMR followed by LS (DMR-LS), fast free-form deformable registration via calculus of variations (F3CV) and F3CV followed by LS (F3CV-LS). The use of an edge-preserving denoising filter called “local M-smoothers” applied to the registered images and combined to all the aforesaid strategies was also tested (fLS, fLSMR, fDMR, fDMR-LS, fF3CV, fF3CV-LS). All these strategies were compared to a rigid registration based on mutual information (MI, fMI). Chronological and anti-chronological registrations were also studied. The various DR strategies were evaluated using a volume-based criterion (i.e. Dice similarity index, DSI) and a voxel-intensity criterion (i.e. correlation coefficient, CC) on a total of 18 different manually contoured volumes. Results: For the DSI analysis, the best three strategies were DMR, fDMR-LS, and fDMR, with the median values of 0.86, 0.85 and 0.85, respectively; corresponding inter-quartile range (IQR) reached 9.6%, 10% and 10.2%. For the CC analysis, the best three strategies were fDMR-LS, DMR-LS and DMR with the median values of 0.97, 0.96 and 0.94, respectively; corresponding IQR reached 11%, 9% and 15%. Concerning the time-sequence analysis, the anti-chronological registration (all deformable strategies pooled) showed a better median DSI value (0.84 vs 0.83, p <0.001) and IQR (11.2% vs 12.4%). For CC, the anti-chronological registration (all deformable strategies pooled) had a slightly lower median value (0.91 vs 0.912, p <0.001) but a better IQR (16.4% vs 21%). Conclusions: The use of fDMR-LS is a good registration strategy for HN-ART as it is the best compromise in terms of median and IQR for both DSI and CC. Even though less robust in terms of CC, DMR is a good alternative. None of the time-sequence appears superior. [Copyright &y& Elsevier]

Abstract: Background and purpose: The planning process in radiotherapy (RT) typically involves the acquisition of a unique set of CT images – and eventually of functional images – which is used for delineation of target volumes (TV) and organs at risk (OAR) and for dose calculation. Restricting the delineation and dose calculation solely on pre-treatment images is an oversimplification as it is only a snapshot of the patient’s anatomy. The objectives of the present study were (1) to assess the consequences of anatomic modification in dose distribution for both TVs and OARs; (2) to assess the potential benefit of adaptive strategies using Helical Tomotherapy (HT); and (3) to compare CT-based and FDG-PET-based adaptive planning strategies. Materials and methods: Ten patients with H&N SCC were imaged before and during concomitant chemo-RT using CT and FDG-PET acquisition after a mean dose of 14.2, 24.5, 35.0 and 44.9Gy. Simultaneous integrated boost IMRT planning was performed using HT. We compared (1) the planned dose distribution, (2) the delivered dose distributions that took into account impact of anatomical modifications on dose distribution, (3) the adaptive dose distributions after replanning to take into account the anatomic modifications and the anatomic or functional GTV shrinkage. Results: There was an increase between the planned and the delivered high dose volumes, which correlated with the slope of the GTV shrinkage. The adaptive high dose volumes were significantly smaller than the delivered ones. The difference between the adaptive and the delivered high dose volume also correlated with the slope of the GTV shrinkage. For both parotid glands combined, the delivered D mean showed a statistical trend for an increase of 4.4% compared to the planned D mean. For the ipsilateral parotid glands, there was a correlation between the D mean gain and the slope of the GTV shrinkage when an adaptive planning was used. For the oral cavity, the adaptive D mean was 10% smaller than the delivered ones. For the PRV around the spinal cord, there was an increase of about 4.5% between the delivered and the planned D 2%. The adaptive planning translated into a decrease in D 2% of 7.2%. The differences between the delivered and planned D 2% and between the adaptive and the delivered D 2% were correlated with the slope of the GTV shrinkage. For the CTVproph and PTVproph coverage, adaptive strategy induced a better dose conformation. No significant difference was observed in the various figures of merit between PET-based plan and CT-based isodose distributions. Conclusions: The dose distribution that is actually delivered to patients significantly differs from what was planned because of anatomic modifications. Adaptive multi-modality IMRT is feasible in H&N tumors and could compensate and improve dose distribution. Some useful surrogate criteria or “flags” are, however, needed to identify patients who might benefit from an adaptive strategy. The optimal adaptive strategy still needs to be defined and prospective studies will have to be conducted to address the safety and the clinical impact of such approaches on patient outcome. [Copyright &y& Elsevier]

Abstract: Purpose: Anatomic changes occur during radiation therapy (RT) for head and neck (H&N) tumors. This study aims at quantifying the volumetric and positional changes of gross tumor volumes (GTV), clinical target volumes (CTV), and organs at risk (OAR). Anatomic (CT) and functional (FDG-PET) imaging were used for the delineation of the GTVs. Materials and methods: Ten patients with H&N tumors treated by chemo-RT were used. Contrast-enhanced CT and FDG-PET were acquired prior and during RT following delivery of mean doses of 14.2, 24.5, 35.0, and 44.9Gy. CT-based GTVs were manually delineated, and PET-based GTVs were segmented using a gradient-based segmentation method. Pre-treatment prophylactic dose CTVs were manually delineated on the pre-treatment CT using consistent and reproducible guidelines. Per-treatment prophylactic CTVs were obtained with an automatic re-contouring method based on deformable registration. For the therapeutic dose CTVs, a 5mm margin was applied around the corresponding GTVs. OARs such as the parotid glands and the submandibular glands were manually delineated on the pre-treatment CT. OARs on the per-treatment CT were automatically delineated using the method used for prophylactic CTVs. The mean slopes of the relative change in volume over time and the mean displacements of the center of mass after 44.9Gy were calculated for each volume. Results: Regarding volumetric changes, CT-based and PET-based primary tumor GTVs decreased at a mean rate of 3.2% and 3.9%/treatment day (td), respectively; nodal GTVs decreased at a mean rate of 2.2%/td. This led to a corresponding decrease of the CT-based and PET-based therapeutic CTVs by 2.4% and 2.5%/td, respectively. CT- and PET-based prophylactic tumor CTVs decreased by an average of 0.7% and 0.5%/td, respectively. No difference in volume shrinkage was observed between CT- and PET-based volumes. The ipsilateral and contralateral parotid glands showed a mean decrease of 0.9% and 1.0%/td, respectively. The ipsilateral and contralateral submandibular glands shrank at a mean rate of 1.5% and 1.3%/td, respectively. Regarding positional changes, CT-based GTVs showed a lateral shift of 1.3mm, PET-based GTVs a posterior shift of 3.4mm and the nodal GTVs a medial shift of 1.0mm, translating into parallel shifts of the therapeutic CTVs. The ipsilateral prophylactic nodal CTV shifted medially by 1.8mm. The ipsilateral parotid gland shifted medially by 3.4mm. The ipsilateral submandibular gland showed a medial shift of 1.7mm and a superior shift of 2.7mm. The contralateral submandibular gland only showed a superior shift of 1.7mm. Conclusions: Volumetric and positional changes in TVs and OARs were observed during concomitant chemo-RT suggesting that adaptive strategies, where patients are re-imaged and possibly re-planned during treatment, are worth evaluating. [Copyright &y& Elsevier]