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Purpose To develop a deep learning model that generates consistent, high-quality lymph node clinical target volumes (CTV) contours for head and neck cancer (HNC) patients, as an integral part of a fully automated radiation treatment planning workflow. Methods and Materials Computed tomography (CT) scans from 71 HNC patients were retrospectively collected and split into training (n = 51), cross-validation (n = 10), and test (n = 10) data sets. All had target volume delineations covering lymph node levels Ia through V (Ia-V), Ib through V (Ib-V), II through IV (II-IV), and retropharyngeal (RP) nodes, which were previously approved by a radiation oncologist specializing in HNC. Volumes of interest (VOIs) about nodal levels were automatically identified using computer vision techniques. The VOI (cropped CT image) and approved contours were used to train a U-Net autosegmentation model. Each lymph node level was trained independently, with model parameters optimized by assessing performance on the cross-validation data set. Once optimal model parameters were identified, overlap and distance metrics were calculated between ground truth and autosegmentations on the test set. Lastly, this final model was used on 32 additional patient scans (not included in original 71 cases) and autosegmentations visually rated by 3 radiation oncologists as being “clinically acceptable without requiring edits,” “requiring minor edits,” or “requiring major edits.” Results When comparing ground truths to autosegmentations on the test data set, median Dice Similarity Coefficients were 0.90, 0.90, 0.89, and 0.81, and median mean surface distance values were 1.0 mm, 1.0 mm, 1.1 mm, and 1.3 mm for node levels Ia-V, Ib-V, II-IV, and RP nodes, respectively. Qualitative scoring varied among physicians. Overall, 99% of autosegmented target volumes were either scored as being clinically acceptable or requiring minor edits (ie, stylistic recommendations, Conclusions We developed a fully automated artificial intelligence approach to autodelineate nodal CTVs for patients with intact HNC. Most autosegmentations were found to be clinically acceptable after qualitative review when considering recommended stylistic edits. This promising work automatically delineates nodal CTVs in a robust and consistent manner; this approach can be implemented in ongoing efforts for fully automated radiation treatment planning.

Purpose To study radiation-induced esophageal expansion as an objective measure of radiation esophagitis in patients with non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy. Methods and Materials Eighty-five patients had weekly intra-treatment CT imaging and esophagitis scoring according to Common Terminlogy Criteria for Adverse Events 4.0, (24 Grade 0, 45 Grade 2, and 16 Grade 3). Nineteen esophageal expansion metrics based on mean, maximum, spatial length, and volume of expansion were calculated as voxel-based relative volume change, using the Jacobian determinant from deformable image registration between the planning and weekly CTs. An anatomic variability correction method was validated and applied to these metrics to reduce uncertainty. An analysis of expansion metrics and radiation esophagitis grade was conducted using normal tissue complication probability from univariate logistic regression and Spearman rank for grade 2 and grade 3 esophagitis endpoints, as well as the timing of expansion and esophagitis grade. Metrics' performance in classifying esophagitis was tested with receiver operating characteristic analysis. Results Expansion increased with esophagitis grade. Thirteen of 19 expansion metrics had receiver operating characteristic area under the curve values >0.80 for both grade 2 and grade 3 esophagitis endpoints, with the highest performance from maximum axial expansion (MaxExp1) and esophageal length with axial expansion ≥30% (LenExp30%) with area under the curve values of 0.93 and 0.91 for grade 2, 0.90 and 0.90 for grade 3 esophagitis, respectively. Conclusions Esophageal expansion may be a suitable objective measure of esophagitis, particularly maximum axial esophageal expansion and esophageal length with axial expansion ≥30%, with 2.1 Jacobian value and 98.6 mm as the metric value for 50% probability of grade 3 esophagitis. The uncertainty in esophageal Jacobian calculations can be reduced with anatomic correction methods.

Purpose To determine whether previously identified quantitative image features (QIFs) based on 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) (co-occurrence matrix energy and solidity) are able to isolate subgroups of patients who would receive a benefit or detriment from dose escalation in terms of overall survival (OS) or progression-free survival (PFS). Methods and Materials Subgroups of a previously analyzed 225 patient cohort were generated with the use of 5-percentile increment cutoff values of disease solidity and primary tumor co-occurrence matrix energy. The subgroups were analyzed with a log-rank test to determine whether there was a difference in OS and PFS between patients treated with 60 to 70 Gy and those receiving 74 Gy. Results In the entire patient cohort, there was no statistical difference in terms of OS or PFS between patients receiving 74 Gy and those receiving 60 to 70 Gy. It was qualitatively observed that as disease solidity and primary co-occurrence matrix energy increased, patients receiving 74 Gy had an improved OS and PFS compared with those receiving 60 to 70 Gy. The opposite trend (detriment of receiving 74 Gy) was also observed regarding low values of disease solidity and primary co-occurrence matrix energy. Conclusions FDG-PET–based QIFs were found to be capable of isolating subgroups of patients who received a benefit or detriment from dose escalation.

Purpose To evaluate early swallowing after intensity-modulated radiotherapy for head and neck squamous cell carcinoma and determine factors correlating with aspiration and/or stricture. Methods and Materials Consecutive patients treated with intensity-modulated radiotherapy with or without chemotherapy between September 2004 and August 2006 at the Dana Farber Cancer Institute/Brigham and Women's Hospital were evaluated with institutional review board approval. Patients underwent swallowing evaluation after completion of therapy; including video swallow studies. The clinical- and treatment-related variables were examined for correlation with aspiration or strictures, as well as doses to the larynx, pharyngeal constrictor muscles, and cervical esophagus. The correlation was assessed with logistic regression analysis. Results A total of 96 patients were evaluated. Their median age was 55 years, and 79 (82%) were men. The primary site of cancer was the oropharynx in 43, hypopharynx/larynx in 17, oral cavity in 13, nasopharynx in 11, maxillary sinus in 2, and unknown primary in 10. Of the 96 patients, 85% underwent definitive RT and 15% postoperative RT. Also, 28 patients underwent induction chemotherapy followed by concurrent chemotherapy, 59 received concurrent chemotherapy, and 9 patients underwent RT alone. The median follow-up was 10 months. Of the 96 patients, 31 (32%) had clinically significant aspiration and 36 (37%) developed a stricture. The radiation dose–volume metrics, including the volume of the larynx receiving ≥50 Gy ( p = 0.04 and p = 0.03, respectively) and volume of the inferior constrictor receiving ≥50 Gy ( p = 0.05 and p = 0.02, respectively) were significantly associated with both aspiration and stricture. The mean larynx dose correlated with aspiration ( p = 0.003). Smoking history was the only clinical factor to correlate with stricture ( p = 0.05) but not aspiration. Conclusion Aspiration and stricture are common side effects after intensity-modulated radiotherapy for head-and-neck squamous cell carcinoma. The dose given to the larynx and inferior constrictors correlated with these side effects.

To improve the target coverage and normal tissue sparing of intensity-modulated radiotherapy (IMRT) for mesothelioma after extrapleural pneumonectomy.Thirteen plans from patients previously treated with IMRT for mesothelioma were replanned using a restricted field technique. This technique was novel in two ways. It limited the entrance beams to 200 degrees around the target and three to four beams per case had their field apertures restricted down to the level of the heart or liver to further limit the contralateral lung dose. New constraints were added that included a mean lung dose of9.5 Gy and volume receivingor=5 Gy of55%.In all cases, the planning target volume coverage was excellent, with an average of 97% coverage of the planning target volume by the target dose. No change was seen in the target coverage with the new technique. The heart, kidneys, and esophagus were all kept under tolerance in all cases. The average mean lung dose, volume receivingor=20 Gy, and volume receivingor=5 Gy with the new technique was 6.6 Gy, 3.0%, and 50.8%, respectively, compared with 13.8 Gy, 15%, and 90% with the previous technique (p0.0001 for all three comparisons). The maximal value for any case in the cohort was 8.0 Gy, 7.3%, and 57.5% for the mean lung dose, volume receivingor=20 Gy, and volume receivingor=5 Gy, respectively.Restricted field IMRT provides an improved method to deliver IMRT to a complex target after extrapleural pneumonectomy. An upcoming Phase I trial will provide validation of these results.

Purpose: To investigate experimentally the impact of different head-and-neck intensity-modulated radiation therapy (IMRT) planning techniques on doses to the skin and shallow targets. Methods and Materials: A semicylindrical phantom was constructed with micro-MOSFET dosimeters (Thomson-Nielson, Ottawa, Ontario, Canada) at 0-, 3-, 6-, 9-, and 12-mm depths. The planning target volume (PTV) was pulled back 0, 3, or 5 mm from the body contour. The IMRT plans were created to maximize PTV coverage, with one of the following strategies: (a) aim for a maximum 110% hotspot, with 115% allowed; (b) aims for a maximum 105% hotspot; (c) aims for a maximum 105% hotspot and 50% of skin to get a maximum 70% of the prescribed dose; and (d) aim for 99% of the PTV volume to receive 90–93% of prescribed dose, with a maximum 105% hotspot, and with the dose to the skin structure minimized. Doses delivered using a linear accelerator were measured. Setup uncertainty was simulated by intentionally shifting the phantom in a range of ±8 mm, and calculating the delivered dose for a range of systematic and random uncertainties. Results: From lowest to highest skin dose, the planning strategies were in the order of c, d, b, and a, but c showed a tendency to underdose tissues at depth. Delivered doses varied by 10–20%, depending on planning strategy. For typical setup uncertainties, cumulative dose reduction to a point 6 mm deep was Conclusions: It is useful to use skin as a sensitive structure, but a minimum dose constraint must be used for the PTV if unwanted reductions in dose to nodes near the body surface are to be avoided. Setup uncertainties are unlikely to give excessive reductions in cumulative dose.

Purpose: To describe the initial experience at Dana-Farber Cancer Institute/Brigham and Women's Hospital with intensity-modulated radiation therapy (IMRT) as adjuvant therapy after extrapleural pneumonectomy (EPP) and adjuvant chemotherapy. Methods and Materials: The medical records of patients treated with IMRT after EPP and adjuvant chemotherapy were retrospectively reviewed. IMRT was given to a dose of 54 Gy to the clinical target volume in 1.8 Gy daily fractions. Treatment was delivered with a dynamic multileaf collimator using a sliding window technique. Eleven of 13 patients received heated intraoperative cisplatin chemotherapy (225 mg/m 2 ). Two patients received neoadjuvant intravenous cisplatin/pemetrexed, and 10 patients received adjuvant cisplatin/pemetrexed chemotherapy after EPP but before radiation therapy. All patients received at least 2 cycles of intravenous chemotherapy. The contralateral lung was limited to a V20 (volume of lung receiving 20 Gy or more) of 20% and a mean lung dose (MLD) of 15 Gy. All patients underwent fluorodeoxyglucose positron emission tomography (FDG-PET) for staging, and any FDG-avid areas in the hemithorax were given a simultaneous boost of radiotherapy to 60 Gy. Statistical comparisons were done using two-sided t test. Results: Thirteen patients were treated with IMRT from December 2004 to September 2005. Six patients developed fatal pneumonitis after treatment. The median time from completion of IMRT to the onset of radiation pneumonitis was 30 days (range 5–57 days). Thirty percent of patients (4 of 13) developed acute Grade 3 nausea and vomiting. One patient developed acute Grade 3 thrombocytopenia. The median V20, MLD, and V5 (volume of lung receiving 5 Gy or more) for the patients who developed pneumonitis was 17.6% (range, 15.3–22.3%), 15.2 Gy (range, 13.3–17 Gy), and 98.6% (range, 81–100%), respectively, as compared with 10.9% (range, 5.5–24.7%) ( p = 0.08), 12.9 Gy (range, 8.7–16.9 Gy) ( p = 0.07), and 90% (range, 66–98.3%) ( p = 0.20), respectively, for the patients who did not develop pneumonitis. Conclusions: Intensity-modulated RT treatment for mesothelioma after EPP and adjuvant chemotherapy resulted in a high rate of fatal pneumonitis when standard dose parameters were used. We therefore recommend caution in the utilization of this technique. Our data suggest that with IMRT, metrics such as V5 and MLD should be considered in addition to V20 to determine tolerance levels in future patients.

Purpose: To determine the effects of Fletcher Suit Delclos ovoid shielding on dose to the bladder and rectum during intracavitary radiotherapy for cervical cancer. Methods and Materials: The Monte Carlo method was used to calculate the dose in 12 patients receiving low-dose-rate intracavitary radiotherapy with both shielded and unshielded ovoids. Cumulative dose-difference surface histograms were computed for the bladder and rectum. Doses to the 2-cm 3 and 5-cm 3 volumes of highest dose were computed for the bladder and rectum with and without shielding. Results: Shielding affected dose to the 2-cm 3 and 5-cm 3 volumes of highest dose for the rectum (10.1% and 11.1% differences, respectively). Shielding did not have a major impact on the dose to the 2-cm 3 and 5-cm 3 volumes of highest dose for the bladder. The average dose reduction to 5% of the surface area of the bladder was 53 cGy. Reductions as large as 150 cGy were observed to 5% of the surface area of the bladder. The average dose reduction to 5% of the surface area of the rectum was 195 cGy. Reductions as large as 405 cGy were observed to 5% of the surface area of the rectum. Conclusions: Our data suggest that the ovoid shields can greatly reduce the radiation dose delivered to the rectum. We did not find the same degree of effect on the dose to the bladder. To calculate the dose accurately, however, the ovoid shields must be included in the dose model.

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.

Purpose The recent introduction of integrated CT/linear accelerator systems may mean that daily CT localization can become a reality in the clinic, possibly allowing further dose escalation to the prostate while limiting unwanted doses to the rectum and bladder. However, the implementation of CT localization is currently impeded by the lack of precise and robust techniques to align the treatment plan with the daily CT images. The purpose of this study was to evaluate a manual alignment technique, in which the gross target volume contours are overlaid on the daily CT images and then shifted to match the structures visible in the images. Methods and materials A total of 28 CT image sets were taken before the standard delivery of intensity-modulated radiotherapy for prostate cancer for 2 patients. Seven observers (four radiation oncologists and three medical physicists) manually shifted the gross target volume contours from the treatment plan to best match the daily CT images. One observer repeated the process 1 week later to evaluate intraobserver variations. The experiment was then repeated, but the CT images from the original treatment plan were used as a reference to reduce interobserver uncertainty when aligning the contours. The shifts in prostate position found by different observers, both with and without reference data, were evaluated using a factorial analysis of variance to determine the standard errors of measurement for the intra- and interobserver uncertainty (SEM intra and SEM inter , respectively). The differences in the SEM for the two groups of observers (radiation oncologists and medical physicists), the two alignment techniques (with and without reference information), and the two patients were evaluated using the t test at 90% confidence levels. Results With no reference information, the SEM inter using one patient data set (Patient 1) was 0.8 mm, 2.0 mm, and 2.2 mm in the right–left (RL), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. The use of the treatment plan as a reference reduced the SEM inter to 0.7 mm, 1.0 mm, and 1.6 mm in the RL, AP, and SI directions, respectively. In Patient 2, localization of the prostate was more difficult; the best SEM inter achieved with this patient was 0.8 mm, 1.9 mm, and 2.0 mm in the RL, AP, and SI directions, respectively. The SEM intra values with Patient 1 were also slightly better than with Patient 2. When reference data were used, the SEM intra value was 0.5 mm, 0.7 mm, and 0.5 mm for Patient 1 and 0.6 mm, 1.0 mm, and 0.7 mm for Patient 2 in the RL, AP, and SI directions, respectively. Despite the larger than expected interobserver variation reported here, the SEM inter was smaller than the typical day-to-day variation in prostate position. The contour alignment technique may still be useful to aid daily prostate localization or in a correction scheme to minimize the effect of target positional error. Conclusion The interobserver uncertainties associated with aligning the gross target volume contours with daily CT images were sufficiently small that this method may be used for daily CT localization of the prostate. The use of a reference image is important to improve the consistency among different users in this technique.