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Objective: This study aims to determine the added value of a geometrically accurate diffusion-weighted (DW-) MRI sequence on the accuracy of gross tumor volume (GTV) delineations, using pathological tumor delineations as a ground truth., Methods: Sixteen patients with laryngeal or hypopharyngeal carcinoma were included. After total laryngectomy, the specimen was cut into slices. Photographs of these slices were stacked to create a 3D digital specimen reconstruction, which was registered to the in vivo imaging. The pathological tumor (tumor HE ) was delineated on the specimen reconstruction. Six observers delineated all tumors twice: once with only anatomical MR imaging, and once (a few weeks later) when DW sequences were also provided. The majority voting delineation of session one (GTV MRI ) and session two (GTV DW-MRI ), as well as the clinical target volumes (CTVs), were compared to the tumor HE ., Results: The mean tumor HE volume was 11.1 cm 3 , compared to a mean GTV MRI volume of 18.5 cm 3 and a mean GTV DW-MRI volume of 15.7 cm 3 . The median sensitivity (tumor coverage) was comparable between sessions: 0.93 (range: 0.61-0.99) for the GTV MRI and 0.91 (range: 0.53-1.00) for the GTV DW-MRI . The CTV volume also decreased when DWI was available, with a mean CTV MR of 47.1 cm 3 and a mean CTV DW-MRI of 41.4 cm 3 . Complete tumor coverage was achieved in 15 and 14 tumors, respectively., Conclusion: GTV delineations based on anatomical MR imaging tend to overestimate the tumor volume. The availability of the geometrically accurate DW sequence reduces the GTV overestimation and thereby CTV volumes, while maintaining acceptable tumor coverage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Advances in diagnostic imaging create opportunities for improved therapeutic targeting of cancer but conceptual thinking about radiotherapy target volume definition and dose-prescription is not keeping up. In this opinion paper we discuss how modern imaging can contribute to new concepts for radiotherapy dose-prescription and target volume definition illustrated by the example of head and neck cancer. These new insights have the potential to significantly reduce radiation associated toxicity and may have important impact on the combination of radiotherapy with systemic cancer therapies., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: To quantify intrafractional motion to determine population-based radiotherapy treatment margins for head-and-neck tumors., Methods: Cine MR imaging was performed in 100 patients with head-and-neck cancer on a 3T scanner in a radiotherapy treatment setup. MR images were analyzed using deformable image registration (optical flow algorithm) and changes in tumor contour position were used to calculate the tumor motion. The tumor motion was used together with patient setup errors (450 patients) to calculate population-based PTV margins., Results: Tumor motion was quantified in 84 patients (12/43/29 nasopharynx/oropharynx/larynx, 16 excluded). The mean maximum (95th percentile) tumor motion (swallowing excluded) was: 2.3 mm in superior, 2.4 mm in inferior, 1.8 mm in anterior and 1.7 mm in posterior direction. PTV margins were: 2.8 mm isotropic for nasopharyngeal tumors, 3.2 mm isotropic for oropharyngeal tumors and 4.3 mm in inferior-superior and 3.2 mm in anterior-posterior for laryngeal tumors, for our institution., Conclusions: Intrafractional head-and-neck tumor motion was quantified and population-based PTV margins were calculated. Although the average tumor motion was small (95th percentile motion <3.0 mm), tumor motion varied considerably between patients (0.1-12.0 mm). The intrafraction motion expanded the CTV-to-PTV with 1.7 mm for laryngeal tumors, 0.6 mm for oropharyngeal tumors and 0.2 mm for nasopharyngeal tumors., (Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: The goal of this study was to improve target definition by deriving modality-specific margins for clinical target volumes (CTV) for laryngeal and hypopharyngeal cancer on CT, MRI and 18-FDG-PET., Material and Methods: Twenty-five patients with T3/T4 laryngeal/hypopharyngeal cancer underwent CT, MRI and 18-FDG-PET scans before laryngectomy. HE-sections were obtained from the surgical specimen and tumor was delineated (tumor HE ). The GTVs on CT and MRI were delineated in consensus. PET-based GTVs were automatically segmented. The three-dimensionally reconstructed specimen was registered to the various images. Modality-specific CTV margins were derived and added to the GTVs to achieve adequate tumor coverage. The resulting CTVs were compared with each other, to tumor HE , and to CTV CT10 constructed on CT with the clinical margin of 10mm., Results: CTV margins of 4.3mm (CT), 6.1mm (MRI) and 5.2mm (PET) were needed to achieve adequate tumor coverage. The median volumes of the resulting modality-specific CTVs were 44ml (CT), 48ml (MRI) and 39ml (PET), while the CTV 10mm was 80ml., Conclusion: For laryngohypopharyngeal tumors, 45-52% target volume reduction compared with CTV 10mm is achievable when modality-specific CTV margins are used. PET-based CTVs were significantly smaller compared to CT- and MRI-based CTVs., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To compare patient-reported xerostomia during daytime and during nighttime with objectively measured parotid and submandibular gland function in a cohort of head-and-neck cancer (HNC) patients treated with RT., Materials and Methods: A cohort of 138 HNC patients underwent objective measurements of parotid (PF) and submandibular (SMF) gland function and completed a xerostomia questionnaire (XQ) before RT, at 6 weeks, 6 months and 1 year after RT. No attempt was made to spare the submandibular gland(s). The XQ contained specific questions concerning the sensation of dry mouth during day- (XD) and nighttime (XN), scored on a 5-point Likert scale. Patients with no or mild (grade 1-3) xerostomia and patients with more severe (grade 4-5) complaints were grouped together., Results: Before RT, no association existed between dry mouth complaints and PF or SMF. At 6 weeks, 6 months and 1 year after RT; 37%, 51% and 36% had grade 4-5 XD and 65%, 64% and 56% had grade 4-5 XN, respectively. Patients with grade 4-5 XD and XN had significantly worse SMF at all time points after RT compared to patients with grade 1-3 XD and XN, while PF was significantly worse only at 6 weeks after RT. In multivariate analyses, SMF was consistently the most important factor related to XN after treatment. PF significantly influenced XD at 6 weeks and 1 year after RT., Conclusions: Differentiating between complaints during day- and nighttime in xerostomia research is necessary. Dry mouth at night is a frequent problem after (parotid-sparing) RT for HNC and is explained by submandibular gland dysfunction. Sparing of the contralateral submandibular gland, in addition to parotid gland sparing, may result in improved patient-reported xerostomia., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: We investigated radiation-induced changes in the salivary glands, 6 weeks after RT, using MRI., Materials and Methods: Eighteen oropharyngeal cancer patients were treated with salivary gland sparing IMRT. All patients received a 3T MRI exam before and 6 weeks after the end of RT, including a T(1)-weighted (T(1)w), a T(2)-weighted (T(2)w), and a dynamic contrast-enhanced (DCE) MRI. For both time points separately, the parotid and submandibular glands were delineated on the MR images. Differences in median signal intensity and signal variation within the glands were tested for significance. Correlations were studied between the MR changes and the planned RT dose., Results: The volume of the glands reduced significantly by 25%. The T(1)w signal decreased by 10% and the T(2)w signal increased by 23%. The k(ep) value decreased, while the v(e) increased. A correlation of the changes in T(2)w signal with the mean dose was found in both glands., Conclusions: Overall radiation-induced changes and volume loss were observed in the parotid and submandibular gland using MR. The observed differences indicated an increased water content such as found in oedema. The overall changes could be related to the mean dose, with a slightly greater impact in the high dose area., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Besides sparing the parotid gland, sparing the submandibular gland is considered to be important in preventing xerostomia in head-and-neck cancer patients. Delineation of the submandibular gland at CT, and even on T(1)- and T(2)-weighted MR images, is difficult, due to low contrast with the surrounding tissues. MR sialography might be used for delineation., Methods and Materials: Sixteen oropharyngeal cancer patients received a CT and MRI exam as part of the standard treatment imaging protocol. Patients were scanned in their five-point RT immobilization mask. The MRI exam included T(1)- and T(2)-weighted MRI scans and an MR sialography scan. Thirty submandibular glands were delineated on only CT, on the combined CT and T(1)- and T(2)-weighted MRI scans and on all MR images. A Wilcoxon signed-rank test was performed to test if the delineated volumes were significantly different., Results: The delineated volume of the submandibular gland was 7.3mL in the CT-delineation, 7.1mL in the CT/MRI-delineation and 8.1mL in the MRI-delineation. The MRI-delineation was significantly larger than the other delineations (p<0.001). The differences were mainly located in the cranial direction., Conclusion: The delineation of the submandibular gland was improved in the cranial direction by using T(1)- and T(2)-weighted MRI and MR sialography, compared to the other delineations., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The benefits of a patient-specific head support, developed to improve immobilization during radiotherapy, were determined in head and neck cancer patients. Cone-beam CTs were registered to the planning CT in five regions. Compared to the standard head support, the individual head support decreased the systematic and random errors of the inter- and intrafraction displacements and reduced deformations., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: The submandibular glands are proposed to be important in preventing xerostomia in head-and-neck cancer patients. We investigated the feasibility of sparing the contralateral submandibular gland (cSMG) by reducing the dose to the contralateral planning target volume (PTV) and by reducing the clinical target volume (CTV)-to-PTV margin., Materials and Methods: Ten oropharyngeal cancer patients with a contralateral elective PTV were included in this planning study, using intensity modulated radiotherapy (IMRT). The effect on the mean dose to the cSMG of reducing the dose coverage to the contralateral elective PTV from 95 to 90% of the prescribed dose (54Gy in 1.8Gy daily fractions) was determined. The influence of reducing the margin for position uncertainty from 5 to 2mm was investigated., Results: The mean dose to the cSMG was reduced from 54Gy to approximately 40Gy if the dose coverage to the contralateral PTV was reduced to 90% of the prescribed dose. The estimated normal tissue complication probability (NTCP) was reduced below 50%. Reducing the margin from 5 to 2mm resulted in a decrease in the mean dose to the cSMG of approximately 6Gy., Conclusions: Reducing the mean dose to the cSMG below 40Gy is possible with a reasonable dose coverage of the contralateral elective PTV.

Background and Purpose: To determine the interobserver variability of clinical target volume delineation of glandular breast tissue and of boost volume in tangential breast irradiation., Patients and Methods: Eighteen consecutive patients with left sided breast cancer treated by breast conserving surgery agreed to participate in our study. Volumes of the glandular breast tissue (CTV breast) and of the boost (CTV boost) were delineated by five observers. We determined 'conformity indices' (CI) and the ratio between the volume of each CTV and the mean volume of all CTVs (CTV ratio). Subsequently we determined the most medial, lateral, anterior, posterior, cranial and caudal extensions both of CTV breast and CTV boost for all observers separately., Results: The mean CI breast was 0.87. For one observer we noted the highest CTV ratio in 17 out of 18 cases. No association was noted between CI breast and menopausal status. The mean CI boost was 0.56. We did not find a relation between the presence or absence of clips and the CI boost. For another observer we noted the lowest CTV boost ratio in 10 out of 17 cases., Conclusions: We recommend that each institute should determine its interobserver variability with respect to CTV breast and CTV boost before implementing the delineation of target volumes by planning CT in daily practice.

Background and Purpose: As the location of the regional lymph nodes (LNs) of the breast varies largely between patients and may be dependant on the position of the arm, adequate localization of these nodes is mandatory in order to fully take advantage of optimized conformal radiotherapy. For this purpose, the anatomical boundaries of the regional lymph node (LN) clinical target volumes (CTVs) for delineation on transverse CT-slices, made in treatment position, were established., Patients and Methods: Anatomical and surgical descriptions of the regional LNs of the breast, as well as a shoulder dissection, were studied. Axial slices of a human cadaver with one arm in abduction and the other in adduction were investigated, to assess the displacement of LNs by abduction of the arm into treatment position. Based on these findings, we defined the anatomical boundaries of the regional LN CTVs visible on transverse CT-slices., Results: Standard anatomical and surgical descriptions appeared to be inadequate for determination of the boundaries of the regional LN CTVs in treatment position. With abduction of the arm, a change in position of all regional LNs, except for the medial supraclavicular LNs and internal mammary LNs, was observed in the anatomical cross-sections. This was also taken into account in our delineation protocol proposal., Conclusions: Anatomically based guidelines for delineation of the regional LN CTVs for loco-regional irradiation of the breast on transverse CT-slices, made in treatment position, have been developed in this study. These could be used as a basis for conformal radiotherapy.

Background and Purpose: To develop a segmental intensity-modulated radiotherapy (IMRT) technique for the treatment of oropharyngeal cancer., Patients and Methods: Eight patients previously treated for oropharyngeal cancer were replanned with segmental IMRT. The dose distribution was optimized using beam geometries consisting of 3, 5, 7 and 9 equiangular beams. The optimization procedure resulted in a theoretical fluence for each beam. In order to vary the number of segments, the optimized fluence was divided into four different equidistant levels. The final dose distribution was calculated using clinically deliverable segments obtained from optimized fluence., Results: For our segmental IMRT technique the dose homogeneity within the target volumes improved when the total number of segments increased and reached a saturation level at approximately 150 segments. Seven beams were sufficient to achieve the saturation level for dose homogeneity. The mean dose to the parotid glands depended on the beam geometry and tumor location and did not depend on the number of segments. On average the mean dose to the contralateral parotid gland was 35.7 Gy (27.1-39.9 Gy) for all seven beam plans., Conclusions: Seven beams are sufficient to achieve an acceptable dose homogeneity within the target volumes and significant parotid sparing. These results will be used to introduce IMRT in routine clinical practice.

Purpose: The aim of this paper is to quantify the importance of the reduction of positioning margins applied to the clinical target volume (CTV) on the dose distribution of the parotid gland for different intensity-modulated radiotherapy (IMRT) strategies for the treatment of oropharyngeal cancer., Methods and Materials: CTVs and organs at risk were delineated in the planning computed tomographic (CT) scans of three patients. Margins of 0, 3, 6 and 9mm were applied to the CTVs in order to obtain the planning target volumes (PTVs). Three IMRT strategies were used to optimize the dose distribution., Results: The analysis of the three IMRT strategies resulted in: (1) an optimal dose distribution in the PTV; (2) optimal dose distribution in the PTV while sparing the parotid gland and (3) more parotid gland sparing but at expense of the dose homogeneity in the PTV. The mean parotid dose increased linearly with increasing margin by approximately 1.3Gy per mm. As a result, the normal complication probability (NTCP) for xerostomia decreased when smaller margins were applied. Reducing the margin from 6 to 3mm resulted in an NTCP reduction of approximately 20%., Conclusion: Reducing the CTV-PTV margin by improving the patient position accuracy may lead to a significant reduction of NTCP for the IMRT treatment of the oropharyngeal tumors and lymph nodes level II.