Search

Purpose: Recurrent or previously irradiated head and neck cancers (HNC) are therapeutically challenging and may benefit from high-dose, highly accurate radiation techniques, such as stereotactic ablative radiation therapy (SABR). Here, we compare set-up and positioning accuracy across HNC subsites to further optimize the treatment process and planning target volume (PTV) margin recommendations for head and neck SABR.Methods and Materials: We prospectively collected data on 405 treatment fractions across 79 patients treated with SABR for recurrent/previously irradiated HNC. First, interfractional error was determined by comparing ExacTrac x-ray to the treatment plan. Patients were then shifted and residual error was measured with repeat x-ray. Next, cone beam computed tomography (CBCT) was compared with ExacTrac for positioning agreement, and final shifts were applied. Lastly, intrafractional error was measured with x-ray before each arc. Results were stratified by treatment site into skull base, neck/parotid, and mucosal.Results: Most patients (66.7%) were treated to 45 Gy in 5 fractions (range, 21-47.5 Gy in 3-5 fractions). The initial mean ± standard deviation interfractional errors were -0.2 ± 1.4 mm (anteroposterior), 0.2 ± 1.8 mm (craniocaudal), and -0.1 ± 1.7 mm (left-right). Interfractional 3-dimensional vector error was 2.48 ± 1.44, with skull base significantly lower than other sites (2.22 vs 2.77; P = .0016). All interfractional errors were corrected to within 1.3 mm and 1.8°. CBCT agreed with ExacTrac to within 3.6 mm and 3.4°. CBCT disagreements and intrafractional errors of >1 mm or >1° occurred at significantly lower rates in skull base sites (CBCT: 16.4% vs 50.0% neck, 52.0% mucosal, P < .0001; intrafractional: 22.0% vs 48.7% all others, P < .0001). Final PTVs were 1.5 mm (skull base), 2.0 mm (neck/parotid), and 1.8 mm (mucosal).Conclusions: Head and neck SABR PTV margins should be optimized by target site. PTV margins of 1.5 to 2 mm may be sufficient in the skull base, whereas 2 to 2.5 mm may be necessary for neck and mucosal targets. When using ExacTrac, skull base sites show significantly fewer uncertainties throughout the treatment process, but neck/mucosal targets may require the addition of CBCT to account for positioning errors and internal organ motion. [ABSTRACT FROM AUTHOR]

Chemoradiotherapy (CRT) combined with immune checkpoint inhibitors (ICIs) is the standard of care for patients with unresectable and locally advanced non-small cell lung cancer. This study aimed to determine whether the addition of ICIs to CRT is associated with an increased risk of pneumonitis. The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for eligible studies published between January 1, 2015, and July 31, 2023. The outcome of interest was the incidence rate of pneumonitis. A random-effects model was used for statistical analysis. A total of 185 studies with 24,527 patients were included. The pooled rate of grade ≥2 pneumonitis for CRT plus ICIs was significantly higher than that for CRT alone (29.6%; 95% CI, 25.7%-33.6% vs 20.2%; 95% CI, 17.7%-22.8%; P <.0001) but not that of grade ≥3 (5.7%; 95% CI, 4.8%-6.6% vs 5.6%; 95% CI, 4.7%-6.5%; P =.64) or grade 5 (0.1%; 95% CI, 0.0%-0.2% vs 0.3%; 95% CI, 0.1%-0.4%; P =.68). The results from the subgroup analyses of prospective studies, retrospective studies, Asian and non-Asian studies, concurrent CRT (cCRT), and durvalumab consolidation were comparable to the overall results. However, CRT or cCRT plus PD-1 inhibitors not only significantly increased the incidence of grade ≥2 but also that of grade ≥3 pneumonitis compared to CRT alone or cCRT plus PD-L1 inhibitors. Compared with CRT alone, durvalumab consolidation after CRT appears to be associated with a higher incidence of moderate pneumonitis and CRT plus PD-1 inhibitors with an increased risk of severe pneumonitis. Nevertheless, these findings are based on observational studies and need to be validated in future large head-to-head studies. [ABSTRACT FROM AUTHOR]

Purpose: To investigate a deformable image registration method to improve soft-tissue contrast in four-dimensional (4D) computed tomography (CT) images of the liver. Methods and Materials: Ten patients with hepatocellular carcinoma underwent 4D CT scan for radiotherapy treatment planning on a positron emission tomography/CT scanner. Four-dimensional CT images were binned into 10 equispaced phases. The exhale phase served as the reference phase, and images from the other nine phases were coregistered to the reference phase image using an intensity-based, automatic deformable image registration method. Then the coregistered images were combined to create a single, high-quality reconstructed CT image at exhale phase as the new reference for target delineation. The extent of image quality enhancement was quantified relative to the original CT by calculating the signal-to-noise ratio and the contrast-to-noise ratio. Results: The soft tissue image contrast was noticeably better after deformable image registration than in the original scans. Signal-to-noise ratios inside the liver region of interest increased for all patients by a factor of 3.0 (range, 2.3–3.7). The improvement in image quality was not linearly proportionate to the number of images averaged. Using only 6 phases can achieve at least 85% of the contrast enhancement that can be achieved using all 10 phases. We also found that contrast enhancement was inversely proportional to the original image quality (p = 0.006), and the contrast enhancement is attained with little loss of spatial resolution. Conclusions: This deformable image registration method is feasible to improve soft-tissue image quality in 4D CT images. [Copyright &y& Elsevier]

Purpose: Auto-propagation of anatomic regions of interest from the planning computed tomography (CT) scan to the daily CT is an essential step in image-guided adaptive radiotherapy. The goal of this study was to quantitatively evaluate the performance of the algorithm in typical clinical applications. Methods and Materials: We had previously adopted an image intensity-based deformable registration algorithm to find the correspondence between two images. In the present study, the regions of interest delineated on the planning CT image were mapped onto daily CT or four-dimensional CT images using the same transformation. Postprocessing methods, such as boundary smoothing and modification, were used to enhance the robustness of the algorithm. Auto-propagated contours for 8 head-and-neck cancer patients with a total of 100 repeat CT scans, 1 prostate patient with 24 repeat CT scans, and 9 lung cancer patients with a total of 90 four-dimensional CT images were evaluated against physician-drawn contours and physician-modified deformed contours using the volume overlap index and mean absolute surface-to-surface distance. Results: The deformed contours were reasonably well matched with the daily anatomy on the repeat CT images. The volume overlap index and mean absolute surface-to-surface distance was 83% and 1.3 mm, respectively, compared with the independently drawn contours. Better agreement (>97% and <0.4 mm) was achieved if the physician was only asked to correct the deformed contours. The algorithm was also robust in the presence of random noise in the image. Conclusion: The deformable algorithm might be an effective method to propagate the planning regions of interest to subsequent CT images of changed anatomy, although a final review by physicians is highly recommended. [Copyright &y& Elsevier]

Purpose: To investigate the dosimetric effects of translational and rotational patient positioning errors on the treatment of spinal and paraspinal metastases using computed tomography image-guided stereotactic body radiotherapy. The results of this study provide guidance for the treatment planning process and recognition of the dosimetric consequences of daily patient treatment setup errors. Methods and Materials: The data from 20 patients treated for metastatic spinal cancer using image-guided stereotactic body radiotherapy were investigated in this study. To simulate the dosimetric effects of residual setup uncertainties, 36 additional plans (total, 756 plans) were generated for each isocenter (total, 21 isocenters) on the planning computed tomography images, which included isocenter lateral, anteroposterior, superoinferior shifts, and patient roll, yaw, and pitch rotations. Tumor volume coverage and the maximal dose to the organs at risk were compared with those of the original plan. Six daily treatments were also investigated to determine the dosimetric effect with or without the translational and rotational corrections. Results: A 2-mm error in translational patient positioning error in any direction can result in >5% tumor coverage loss and >25% maximal dose increase to the organs at risk. Rotational correction is very important for patients with multiple targets and for the setup of paraspinal patients when the isocenter is away from bony structures. Compared with the original plans, the daily treatment data indicated that translational adjustments could correct most of the setup errors to mean divergences of −1.4% for tumor volume coverage and −0.3% for the maximal dose to the organs at risk. Conclusion: For the best dosimetric results, spinal stereotactic treatments should have setup translational errors of ≤1 mm and rotational errors of ≤2°. [Copyright &y& Elsevier]

Purpose: Daily prostate deformation hinders accurate calculation of dose, especially to intraprostatic targets. We implemented a three-dimensional deformable registration algorithm to aid dose tracking for targeted prostate radiotherapy. Methods and Materials: The algorithm registers two computed tomography (CT) scans by iteratively minimizing their differences in image intensity. For validation, we measured the accuracy in registering (a) a pelvic CT set to its mathematically deformed counterpart, (b) CT scans of a deformable pelvic phantom with and without an endorectal balloon inflated, to simulate intraprostatic targets, 23 CT-opaque seeds were embedded in the prostate, and (c) two pelvic CT scans of a patient obtained on 2 separate days. Results: The mean (SD) error in registering the pelvic CT set to its transformed set was 0.5 mm (1.5), with correlation coefficient improvement from 0.626 to 0.991. Using the deformable pelvic phantom, the correlation coefficient improved from 0.543 to 0.816 after registration. The mean (SD) error in tracking the intraprostatic seeds was 0.8 mm (0.5). The correlation coefficient improved from 0.610 to 0.944 after registration of the two patient CT sets. Conclusion: The algorithm had an accuracy of about 1 mm. It could be used for optimizing dose calculation and delivery for prostate radiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Recent imaging studies have demonstrated that there can be significant changes in anatomy from day to day and over the course of radiotherapy as a result of daily positioning uncertainties and physiologic and clinical factors. There are a number of strategies to minimize such changes, reduce their impact, or correct for them. Measures to date have included improved immobilization of external and internal anatomy or adjustment of positions based on portal or ultrasound images. Perhaps the most accurate way is to use CT image–guided radiotherapy, for which the possibilities range from simple correction of setup based on daily CT images to on-line near real-time intensity modulated radiotherapy (IMRT) replanning. In addition, there are numerous intermediate possibilities. In this paper, we report the development of one such intermediate method that takes into account anatomic changes by deforming the intensity distributions of each beam based on deformations of anatomy as seen in the beam''s-eye–view. Methods and materials: The intensity distribution deformations are computed based on anatomy deformations discerned from the changes in the current image relative to a reference image (e.g., the pretreatment CT scan). First, a reference IMRT plan is generated based on the reference CT image. A new CT image is acquired using an in-room CT for every fraction. The anatomic structure contours are obtained for the new image. (For this article, these contours were manually drawn. When image guided IMRT methods are implemented, anatomic structure contours on subsequent images will likely be obtained with automatic or semiautomatic means. This could be achieved by, for example, first deforming the original CT image to match today''s image, and then using the same deformation transformation to map original contours to today''s image.) The reference intensity distributions for each beam are then deformed so that the projected geometric relationship within the beam''s-eye–view between the anatomy (both target and normal tissues) extracted from the reference image and the reference intensity distribution is the same as (or as close as possible to) the corresponding relationship between anatomy derived from today''s image and the newly deformed intensity distributions. To verify whether the dose distributions calculated using the deformed intensity distributions are acceptable for treatment as compared to the original intensity distributions, the deformed intensities are transformed into leaf sequences, which are then used to compute intensity and dose distributions expected to be delivered. The corresponding dose–volume histograms and dose–volume and dose–response indices are also computed. These data are compared with the corresponding data derived (a) from the original treatment plan applied to the original image, (b) from the original treatment plan applied to today''s image, and (c) from a new full-fledged IMRT plan designed based on today''s image. Results: Depending on the degree of anatomic changes, the use of an IMRT plan designed based on the original planning CT for the treatment of the current fraction could lead to significant differences compared to the intended dose distributions. CT-guided setup compared to the setup based on skin marks or bony landmarks may improve dose distributions somewhat. Replanning IMRT based on the current fraction''s image yields the best physically deliverable plan (the “gold standard”). For the prostate and head-and-neck examples studied as proof of principle, the results of deforming intensities within each beam based on the anatomy seen in the beam''s-eye–view are a good approximation of full-fledged replanning compared with other alternatives. Conclusions: Our preliminary results encourage us to believe that deforming intensities taking into account deformation in the anatomy may be a rapid way to produce new treatment plans on-line in near real-time based on daily CT images. The methods we have developed need to be applied to a group of patients for both prostate and head-and-neck cases to confirm the validity of our approach. [Copyright &y& Elsevier]

Purpose: To evaluate the outcomes associated with stereotactic body radiotherapy (SBRT) in the management of spinal metastases from renal cell carcinoma (RCC). Methods and Materials: SBRT was used in the treatment of patients with spinal metastases from RCC. Patients received either 24 Gy in a single fraction, 27 Gy in three fractions, or 30 Gy delivered in five fractions. Effectiveness of SBRT with respect to tumor control and palliation of pain was assessed using patient-reported outcomes. Results: A total of 48 patients with 55 spinal metastases were treated with SBRT with a median follow-up time of 13.1 months (range, 3.3–54.5 months). The actuarial 1-year spine tumor progression free survival was 82.1%. At pretreatment baseline, 23% patients were pain free; at 1 month and 12 months post-SBRT, 44% and 52% patients were pain free, respectively. No Grade 3-4 neurologic toxicity was observed. Conclusions: The data support SBRT as a safe and effective treatment modality that can be used to achieve good tumor control and palliation of pain associated with RCC spinal metastases. Further evaluation with randomized trials comparing SBRT to conventional radiotherapy may be warranted. [Copyright &y& Elsevier]

Purpose: To quantify the interfraction variability in prostate and seminal vesicle (SV) positions during a course of intensity-modulated radiotherapy (IMRT) using an integrated computed tomography (CT)–linear accelerator system and to assess the impact of rectal and bladder volume changes. Methods and Materials: We studied 15 patients who had undergone IMRT for prostate carcinoma. Patients had one pretreatment planning CT scan followed by three in-room CT scans per week using a CT-on-rails system. The prostate, bladder, rectum, and pelvic bony anatomy were contoured in 369 CT scans. Using the planning CT scan as a reference, the volumetric and positional changes were analyzed in the subsequent CT scans. Results: For all 15 patients, the mean systematic internal prostate and SV variation was 0.1 ± 4.1 mm and 1.2 ± 7.3 mm in the anteroposterior axis, −0.5 ± 2.9 mm and −0.7 ± 4.5 mm in the superoinferior axis, and 0.2 ± 0.9 mm and −0.9 ± 1.9 mm in the lateral axis, respectively. The mean magnitude of the three-dimensional displacement vector was 4.6 ± 3.5 mm for the prostate and 7.6 ± 4.7 mm for the SVs. The rectal and bladder volume changes during treatment correlated with the anterior and superior displacement of the prostate and SVs. Conclusion: The dominant prostate and SV variations occurred in the anteroposterior and superoinferior directions. The systematic prostate and SV variation between the treatment planning CT and daily therapy as a result of the rectal and bladder volume changes emphasizes the need for daily directed target localization and/or immobilization techniques. [Copyright &y& Elsevier]

Purpose: To compare the effectiveness of daily ultrasound (US)- and computed tomography (CT)-guided alignments with an off-line correction protocol using daily bone alignment plus a correction factor for systematic internal prostate displacement (CFID). Methods and Materials: Ten prostate cancer patients underwent CT scans three times weekly using an integrated CT-linear accelerator system, followed by alignment using US for daily radiotherapy. Intensity-modulated radiotherapy plans were designed with our current clinical margins. The treatment plan was copied onto the repeat CT images and aligned using several methods: (1) bone alignment plus CFID after three off-line CT scans (bone+3CT), (2) bone alignment plus CFID after six off-line CT scans (bone+6CT), (3) US alignment, and (4) CT alignment. The accuracy of the repeated US and CT measurements to determine the CFID was compared. The target dosimetric effect was quantified. Results: The CFID for internal systematic prostate displacements was more accurately measured with limited repeat CT scans than with US (residual error, 0.0 ± 0.7 mm vs. 2.0 ± 3.2 mm). Bone+3CT, bone+6CT, and US provided equivalent prostate and seminal vesicle dose coverage, but bone+3CT and bone+6CT produced more precise daily alignments. Daily CT alignment provided the greatest target dose coverage. Conclusion: Daily bone alignment plus CFID for internal systematic prostate displacement provided better daily alignment precision and equivalent dose coverage compared with daily US alignment. The CFID should be based on at least three repeat CT scans, which could be collected before the start of treatment or during the first 3 treatment days. Daily bone alignment plus CFID provides another option for accurate prostate cancer patient positioning. [Copyright &y& Elsevier]

Purpose: To quantify the differences between planned and delivered parotid gland and target doses, and to assess the benefits of daily bone alignment for head and neck cancer patients treated with intensity-modulated radiotherapy (IMRT).Methods and Materials: Eleven head and neck cancer patients received two CT scans per week with an in-room CT scanner over the course of their radiotherapy. The clinical IMRT plans, designed with 3-mm to 4-mm planning margins, were recalculated on the repeat CT images. The plans were aligned using the actual treatment isocenter marked with radiopaque markers (BB) and bone alignment to the cervical vertebrae to simulate image-guided setup. In-house deformable image registration software was used to map daily dose distributions to the original treatment plan and to calculate a cumulative delivered dose distribution for each patient.Results: Using conventional BB alignment led to increases in the parotid gland mean dose above the planned dose by 5 to 7 Gy in 45% of the patients (median, 3.0 Gy ipsilateral, p = 0.026; median, 1.0 Gy contralateral, p = 0.016). Use of bone alignment led to reductions relative to BB alignment in 91% of patients (median, 2 Gy; range, 0.3-8.3 Gy; 15 of 22 parotids improved). However, the parotid dose from bone alignment was still greater than planned (median, 1.0 Gy, p = 0.007). Neither approach affected tumor dose coverage.Conclusions: With conventional BB alignment, the parotid gland mean dose was significantly increased above the planned mean dose. Using daily bone alignment reduced the parotid dose compared with BB alignment in almost all patients. A 3- to 4-mm planning margin was adequate for tumor dose coverage. [ABSTRACT FROM AUTHOR]

Purpose: To investigate strategies for designing compensator-based 3D proton treatment plans for mobile lung tumors using four-dimensional computed tomography (4DCT) images. Methods and Materials: Four-dimensional CT sets for 10 lung cancer patients were used in this study. The internal gross tumor volume (IGTV) was obtained by combining the tumor volumes at different phases of the respiratory cycle. For each patient, we evaluated four planning strategies based on the following dose calculations: (1) the average (AVE) CT; (2) the free-breathing (FB) CT; (3) the maximum intensity projection (MIP) CT; and (4) the AVE CT in which the CT voxel values inside the IGTV were replaced by a constant density (AVE_RIGTV). For each strategy, the resulting cumulative dose distribution in a respiratory cycle was determined using a deformable image registration method. Results: There were dosimetric differences between the apparent dose distribution, calculated on a single CT dataset, and the motion-corrected 4D dose distribution, calculated by combining dose distributions delivered to each phase of the 4DCT. The AVE_RIGTV plan using a 1-cm smearing parameter had the best overall target coverage and critical structure sparing. The MIP plan approach resulted in an unnecessarily large treatment volume. The AVE and FB plans using 1-cm smearing did not provide adequate 4D target coverage in all patients. By using a larger smearing value, adequate 4D target coverage could be achieved; however, critical organ doses were increased. Conclusion: The AVE_RIGTV approach is an effective strategy for designing proton treatment plans for mobile lung tumors. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to compare the dosimetric consequences of 4 treatment delivery techniques for prostate cancer patients treated with intensity-modulated radiotherapy (IMRT). Methods and Materials: During an 8-week course of radiotherapy, 10 patients underwent computed tomography (CT) scans 3 times per week (243 total) before daily treatment with a CT-linear accelerator. Treatment delivery was simulated by realigning a fixed-margin treatment plan on each CT scan and calculating doses. The alignment methods were those based on the following: skin marks, bony registration, ultrasonography (US), and in-room CT. For the last two methods, prostate was the alignment target. The dosimetric effects of these alignment methods on the prostate, seminal vesicles, rectum, and bladder were compared. The average daily minimum dose to 0.1 cm3 was used as the metric for target coverage. Results: Skin and bone alignments provided acceptable prostate coverage for only 70% of patients, US alignment for 90%, and CT alignment for 100%. CT-based alignment of the prostate provided seminal vesicle (SV) coverage of > or = 69 Gy for all patients; US and bone alignments provided SV coverage of > or = 60 Gy. This SV coverage may be acceptable for early-stage cancer (equivalent SV dose = 55.8 Gy at 1.8 Gy per fraction), but unacceptable for late-stage cancer (SV dose = 75.6 Gy). At 75.6 Gy, the acceptable rate for SV coverage was 40% for skin and bone alignments, 70% for US, and 80% for CT. Conclusions: Direct target alignment methods (US and CT) provided better target coverage. CT-guided alignment provided the best and most consistent dosimetric coverage. A larger planning target volume margin is needed for SV coverage when the alignment target is the prostate. [ABSTRACT FROM AUTHOR]

Purpose: To propose and evaluate online adaptive radiation therapy (ART) using in-room computed tomography (CT) imaging that detects changes in the target position and shape of the prostate and seminal vesicles (SVs) and then automatically modifies the multileaf collimator (MLC) leaf pairs in a slice-by-slice fashion. Methods and Materials: For intensity-modulated radiation therapy (IMRT) using a coplanar beam arrangement, each MLC leaf pair projects onto a specific anatomic slice. The proposed strategy assumes that shape deformation is a function of only the superior-inferior (SI) position. That is, there is no shape change within a CT slice, but each slice can be displaced in the anteroposterior (AP) or right-left (RL) direction relative to adjacent slices. First, global shifts (in SI, AP, and RL directions) were calculated by three-dimensional (3D) registration of the bulk of the prostate in the treatment planning CT images with the daily CT images taken immediately before treatment. Local shifts in the AP direction were then found using slice-by-slice registration, in which the CT slices were individually registered. The translational shift within a slice could then be projected to a translational shift in the position of the corresponding MLC leaf pair for each treatment segment for each gantry angle. Global shifts in the SI direction were accounted for by moving the open portal superiorly or inferiorly by an integral number of leaf pairs. The proposed slice-by-slice registration technique was tested by using daily CT images from 46 CT image sets (23 each from 2 patients) taken before the standard delivery of IMRT for prostate cancer. A dosimetric evaluation was carried out by using an 8-field IMRT plan. Results: The shifts and shape change of the prostate and SVs could be separated into 3D global shifts in the RL, AP, and SI directions, plus local shifts in the AP direction, which were different for each CT slice. The MLC leaf positions were successfully modified to compensate for these global shifts and local shape variations. The ART method improved geometric coverage of the prostate and SVs compared with the couch-shift method, particularly for the superior part of the prostate and all the SVs, for which the interfraction shape change was the largest. The dosimetric comparison showed that the ART method covered the target better and reduced the rectal dose more than a simple couch-translation method. Conclusions: ART corrected for interfraction changes in the position and shape of the prostate and SVs and gave dose distributions that were considerably closer to the planned dose distributions than could be achieved with simple alignment strategies that neglect shape change. The ART proposed in this investigation requires neither contouring of the daily CT images nor extensive calculations; therefore, it may prove to be an effective and clinically practical solution to the problem of interfraction shape changes. [ABSTRACT FROM AUTHOR]

Purpose: Many patients receiving fractionated radiotherapy (RT) for head-and-neck cancer have marked anatomic changes during their course of treatment, including shrinking of the primary tumor or nodal masses, resolving postoperative changes/edema, and changes in overall body habitus/weight loss. We conducted a pilot study to quantify the magnitude of these anatomic changes with systematic CT imaging.Methods and materials: Fourteen assessable patients were enrolled in this pilot study. Eligible patients had to have a pathologic diagnosis of head-and-neck cancer, be treated with definitive external beam RT, and had have gross primary and/or cervical nodal disease measuring at least 4 cm in maximal diameter. All patients were treated using a new commercial integrated CT-linear accelerator system (EXaCT) that allows CT imaging at the daily RT sessions while the patient remains immobilized in the treatment position. CT scans were acquired three times weekly during the entire course of RT, and both gross tumor volumes (GTVs: primary tumor and involved lymph nodes) and normal tissues (parotid glands, spinal canal, mandible, and external contour) were manually contoured on every axial slice. Volumetric and positional changes relative to a central bony reference (the center of mass of the C2 vertebral body) were determined for each structure.Results: Gross tumor volumes decreased throughout the course of fractionated RT, at a median rate of 0.2 cm3 per treatment day (range, 0.01–1.95 cm3/d). In terms of the percentage of the initial volume, the GTVs decreased at a median rate of 1.8%/treatment day (range, 0.2–3.1%/d). On the last day of treatment, this corresponded to a median total relative loss of 69.5% of the initial GTV (range, 9.9–91.9%). In addition, the center of the mass of shrinking tumors changed position with time, indicating that GTV loss was frequently asymmetric. At treatment completion, the median center of the mass displacement (after corrections for daily setup variation) was 3.3 mm (range, 0–17.3 mm). Parotid glands also decreased in volume (median, 0.19 cm3/d range, 0.04–0.84 cm3/d), and generally shifted medially (median, 3.1 mm; range, 0–9.9 mm) with time. This medial displacement of the parotid glands correlated highly with the weight loss that occurred during treatment.Conclusion: Measurable anatomic changes occurred throughout fractionated external beam RT for head-and-neck cancers. These changes in the external contour, shape, and location of the target and critical structures appeared to be significant during the second half of treatment (after 3–4 weeks of treatment) and could have potential dosimetric impact when highly conformal treatment techniques are used. These data may, therefore, be useful in the development of an adaptive RT scheme (periodic adjustment of the conformal treatment plan) that takes into account such treatment-related anatomic changes. In theory, such a strategy would maximize the therapeutic ratio of RT. [Copyright &y& Elsevier]