Deformable registration
Assessment by a deformable registration method of the volumetric and positional changes of target volumes and organs at risk in pharyngo-laryngeal tumors treated with concomitant chemo-radiation

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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 44.9 Gy. 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 5 mm 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 44.9 Gy 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 1.3 mm, PET-based GTVs a posterior shift of 3.4 mm and the nodal GTVs a medial shift of 1.0 mm, translating into parallel shifts of the therapeutic CTVs. The ipsilateral prophylactic nodal CTV shifted medially by 1.8 mm. The ipsilateral parotid gland shifted medially by 3.4 mm. The ipsilateral submandibular gland showed a medial shift of 1.7 mm and a superior shift of 2.7 mm. The contralateral submandibular gland only showed a superior shift of 1.7 mm.

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.

Section snippets

Patient selection

The set of images used was acquired in a previously reported study [23]. Briefly, 10 patients with stage III-IV (1997 AJCC Classification) H&N squamous cells carcinoma (SCC) were imaged before (pre-treatment) and weekly during (per-treatment) concomitant chemo-RT. Patients’ characteristics are shown in Table 1. All patients were treated by radical concomitant chemo-RT (70 Gy in 7 weeks for the therapeutic PTVs and 50 Gy in 5 weeks for the prophylactic PTVs; concomitant chemotherapy with

Metric analysis

All volumes were calculated from the contoured axial slices using IMRE-viewer. The slopes of the relative change in volume over time for each organ and each patient were calculated using linear regression analyses. Then the mean slope for each volume was calculated and bilateral paired t-test for parametric data, and the Wilcoxon Signed-Rank test for non-parametric data were performed. CT-based and PET-based slopes were compared to each other using the bilateral paired t-test for parametric

Volumetric analysis

The mean relative slopes of the volume variations, confidence intervals and performed statistical tests are described in Table 2.

The GTVT,CT, GTVT,PET and GTVN,CT decreased throughout fractionated RT (Fig. 2), at a mean rate of 3.2 (p < 0.01, paired t-test), 3.9 (p = 0.005, Wilcoxon) and 2.2% (p = 0.018, Wilcoxon) per treatment day, respectively . This decrease in GTVs translated in a parallel decrease of the corresponding CTVther,T,CT, CTVther,T,PET and CTVther,N,CT of 2.6 (p < 0.001, paired t-test),

Discussion

The collected data show that during fractionated concomitant chemo-RT for locally advanced H&N SCC marked volumetric and positional modifications occur in TVs and OARs. These changes most likely resulted from tumor response resulting in changes in patients’ anatomy, as well as a consequence of patients’ morbidity encountered during treatment, e.g. weight loss. In this study as in other published data, the volume decrease with dose was fitted assuming a linear relationship [7]. This is likely an

Conclusions

Major volumetric and positional changes in TVs and OARs were observed during fractionated concomitant chemo-RT treatments. Such modifications affect the parotid glands, the submandibular glands, the prophylactic and the therapeutic CTVs for both the primary tumors and the lymph nodes. Such volumetric and positional modifications are likely to affect the dose distribution, and thus support the evaluation of adaptive dose re-planning solutions.

Acknowledgements

Pierre Castadot is a Research Fellow with the F.N.R.S. (Fonds National de la Recherche Scientifique). John A. Lee and Xavier Geets are Postdoctoral Researchers with the F.N.R.S. (Fonds National de la Recherche Scientifique). Nicolas Christian is a research fellow with the F.R.I.A. (Fonds pour la formation à la Recherche dans l’Industrie et dans l’Agriculture).

This work is supported by a grant from the Belgian Federation against Cancer (convention #SCIE 2003-23FR), by a grant from the

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