Development of programs to predict the occurrence of mucositis from digital imaging and communications in medicine data by machine learning in head and neck volumetric modulated radiotherapy.

Volumetric modulated arc therapy (VMAT) with cisplatin for head and neck cancer is often accompanied by symptoms of pharyngeal and oral mucositis. However, no standard medical program exists for the prevention and treatment of mucositis, and the mechanisms of mucositis have not yet been fully proven. Therefore, adaptive radiotherapy (ART), which is a re-planning process, is administered when severe mucositis develops during the treatment period. We extracted the treatment plans of patients who developed severe mucositis from DICOM data and used machine learning to determine its quantitative features. This study aimed to develop a machine learning program that can predict the development of mucositis requiring ART. This study included 61 patients who received concurrent chemotherapy and radiotherapy (RT). For each patient, the equivalent square field size of each segmental irradiation field used for VMAT, dose per segment (Gy), clinical target volume high, and mean dose of the oral cavity (Gy) were calculated. Furthermore, 671 five-dimensional lists were generated from the acquired data. Support vector machine (SVM) and K-nearest neighbor (KNN) were used for machine learning. For the accuracy score, the test size was varied from 10% to 90%, and the random number of data extracted in each test size was further varied from 1 to 100 to calculate a mean accuracy score. The mean accuracy scores of SVM and KNN were 0.981 ± 0.020 and 0.972 ± 0.033, respectively. The presence or absence of ART for mucositis was classified with high accuracy. The classification of the five-dimensional list was implemented with high accuracy, and a program was constructed to predict the onset of mucositis requiring ART before treatment began. This study suggests that it may support preventive measures against mucositis and the completion of RT without having to re-plan.

Upper-neck irradiation versus standard whole-neck irradiation in nasopharyngeal carcinoma: A systematic review and meta-analysis.

PURPOSE: To evaluate the role of upper-neck irradiation versus standard whole-neck irradiation in patients with N0-1 nasopharyngeal carcinoma. METHODS: We conducted a PRISMA guideline based systematic review and meta-analysis. Randomized clinical trials assessing upper-neck irradiation versus whole-neck irradiation with or without chemotherapy in non-metastatic N0-1 nasopharyngeal carcinoma patients were identified. The studies were searched on the PubMed, Embase and Cochrane library up to March 2022. Survival outcomes, including overall survival, distant metastasis-free survival and relapse-free survival, and toxicities rate were evaluated. RESULTS: There were two randomized clinical trials with 747 samples finally included. Upper-neck irradiation had similar overall survival (hazard ratio = 0.69, 95% confidence interval = 0.37-1.30), distant metastasis-free survival (hazard ratio = 0.92, 95% confidence interval = 0.53-1.60) and relapse-free survival (risk ratio = 1.03, 95% confidence interval = 0.69-1.55) compared to whole-neck irradiation. No differences in both acute and late toxicities were recorded between upper-neck irradiation and whole-neck irradiation. CONCLUSION: This meta-analysis supports the potential role of upper-neck irradiation in this population of patients. Further research is needed to confirm results.

Upper-Neck Versus Whole-Neck Irradiation at the Contralateral Uninvolved Neck in Patients With Unilateral N3 Nasopharyngeal Carcinoma.

PURPOSE: Upper-neck irradiation (UNI) at the uninvolved neck has shown similar regional relapse-free survival as standard whole-neck irradiation (WNI) in patients with N0-1 nasopharyngeal carcinoma. However, whether UNI at the contralateral uninvolved neck is feasible in unilateral N3 disease, defined as >6 cm and/or below the caudal border of the cricoid cartilage, remains unclear. METHODS AND MATERIALS: Data for 291 patients with nasopharyngeal carcinoma with unilateral N3 disease who were treated with intensity modulated radiation therapy from 2009 to 2015 were retrospectively analyzed. Among them, 190 received bilateral WNI (WNI group); the remaining 101 received WNI at the involved neck and UNI at the contralateral uninvolved neck (UNI group). Survival rates were estimated using the Kaplan-Meier method, and differences between groups were compared using the log rank tests. RESULTS: The median follow-up was 79.4 months (interquartile range, 56.0-89.3). Twenty-five patients had regional lymph node relapses (UNI: 10.9%, 11/101 vs WNI: 7.4%, 14/190; P = .31). Of these, 23 patients relapsed within the previously involved neck regions, while only 2 patients had relapses in the contralateral uninvolved neck (1 each in the UNI and WNI groups). Five-year regional relapse-free survival rates were similar between groups (89.7% vs 92.7%, P = .29). Similar between-group findings were also observed for 5-year overall survival (76.1% vs 80.4%, P = .40), distant metastasis-free survival (74.9% vs 79.2%, P = .44), and local relapse-free survival (95.6% vs 94.7%, P = .64). Furthermore, oncologic outcomes in subgroup and multivariable analyses were similar between groups. CONCLUSIONS: Regional control and survival outcomes were comparable in UNI at the contralateral uninvolved neck and standard WNI in patients with nasopharyngeal carcinoma with unilateral N3 disease. Our findings provide evidence for future radiation therapy guidelines of nasopharyngeal carcinoma.

Radiotherapy dose-volume parameters predict facial lymphedema after concurrent chemoradiation for nasopharyngeal carcinoma.

BACKGROUND: To investigate risk factors for developing radiation-associated facial lymphedema (FL) in nasopharyngeal carcinoma (NPC) patients after concurrent chemoradiation (CCRT). METHODS: Clinical data from 87 patients who underwent definitive CCRT for NPC in 2010-2018 was retrospectively evaluated. FL severity was graded using MD Anderson Cancer Center head and neck lymphedema rating scale. Logistic regression analysis was used to examine the factors associated with the presence of moderate/severe FL (grade ≥ 2). RESULTS: At a median follow-up of 34 months (range, 18-96), 26/87 (29.9%) patients experienced grade ≥ 2 FL. A majority (84.6%) was experienced grade ≥ 2 FL 3-6 months after CCRT. Mean dose to the level IV, level I-VII neck node and N stage were significantly correlated with grade ≥ 2 FL at univariate analysis. At multivariate analysis, mean dose of level IV neck node (hazard ratio [HR], 1.238; 95% confidence interval [CI] = 1.084-1.414; p = 0.002) and level I-VII neck node (HR, 1.384; 95% CI = 1.121-1.708; p = 0.003) were independent predictors. Receiver Operating Characteristics (ROC) curve analysis showed that cut-off value of mean level IV neck node dose was 58.7 Gy (area under the curve [AUC] = 0.726; 95% CI = 0.614-0.839, p = 0.001) and mean level I-VII neck node dose was 58.6 Gy (AUC = 0.720; 95% CI = 0.614-0.826, p = 0.001) for grade ≥ 2 FL. CONCLUSIONS: Keeping mean dose to the level IV and level I-VII below 58.7 Gy and 58.6 Gy may reduce the likelihood of moderate/severe FL after CCRT for NPC.

Radiotherapy as Elective Treatment of the Node-negative Neck in Oral Squamous Cell Cancer.

BACKGROUND/AIM: Previous studies of node-negative oral squamous cell carcinoma have shown a benefit of elective neck dissection compared to observation. Evidence for radiotherapy as single-modality elective treatment of the node-negative neck is so far lacking. PATIENTS AND METHODS: In a retrospective material of 420 early-stage oral cancers from 2000 to 2016, overall survival, disease-free survival, and regional relapse-free survival were calculated with the Kaplan-Meier method. RESULTS: At five years, overall survival was 59.7%, disease-specific survival was 77.2%, and regional relapse-free survival was 83.5%. Among those with adjuvant treatment of the neck after surgery of T1-T2 tumours during 2009-2016, regional relapse-free survival at five years was 85.7% for elective radiotherapy of the neck and 87.4% for elective neck dissection. CONCLUSION: Elective radiotherapy to the neck with a modern technique and adequate dose might be an alternative to neck dissection for patients with early-stage oral squamous cell cancer.

Geometric and dosimetric impact of 3D generative adversarial network-based metal artifact reduction algorithm on VMAT and IMPT for the head and neck region.

BACKGROUND: We investigated the geometric and dosimetric impact of three-dimensional (3D) generative adversarial network (GAN)-based metal artifact reduction (MAR) algorithms on volumetric-modulated arc therapy (VMAT) and intensity-modulated proton therapy (IMPT) for the head and neck region, based on artifact-free computed tomography (CT) volumes with dental fillings. METHODS: Thirteen metal-free CT volumes of the head and neck regions were obtained from The Cancer Imaging Archive. To simulate metal artifacts on CT volumes, we defined 3D regions of the teeth for pseudo-dental fillings from the metal-free CT volumes. HU values of 4000 HU were assigned to the selected teeth region of interest. Two different CT volumes, one with four (m4) and the other with eight (m8) pseudo-dental fillings, were generated for each case. These CT volumes were used as the Reference. CT volumes with metal artifacts were then generated from the Reference CT volumes (Artifacts). On the Artifacts CT volumes, metal artifacts were manually corrected for using the water density override method with a value of 1.0 g/cm3 (Water). By contrast, the CT volumes with reduced metal artifacts using 3D GAN model extension of CycleGAN were also generated (GAN-MAR). The structural similarity (SSIM) index within the planning target volume was calculated as quantitative error metric between the Reference CT volumes and the other volumes. After creating VMAT and IMPT plans on the Reference CT volumes, the reference plans were recalculated for the remaining CT volumes. RESULTS: The time required to generate a single GAN-MAR CT volume was approximately 30 s. The median SSIMs were lower in the m8 group than those in the m4 group, and ANOVA showed a significant difference in the SSIM for the m8 group (p < 0.05). Although the median differences in D98%, D50% and D2% were larger in the m8 group than the m4 group, those from the reference plans were within 3% for VMAT and 1% for IMPT. CONCLUSIONS: The GAN-MAR CT volumes generated in a short time were closer to the Reference CT volumes than the Water and Artifacts CT volumes. The observed dosimetric differences compared to the reference plan were clinically acceptable.

Cervical Fibrosis as a Predictor of Dysphagia.

OBJECTIVE: Radiotherapy of head and neck cancer (HNCA) causes dysfunction through radiation-induced fibrosis (RIF). We hypothesize that the degree of cervical fibrosis is associated with swallowing dysfunction. This study evaluated the association between cervical fibrosis and swallowing dysfunction in patients after radiation therapy for HNCA. STUDY DESIGN: Cross sectional study. METHODOLOGY: A convenience sample of patients with dysphagia who were at least 1 year post radiation therapy for HNCA underwent simultaneous cervical ultrasound (US) and video-fluroscopic swallow study (VFSS). US determinants of fibrosis were measurements of sternocleidomastoid fascia (SCMF) thickness bilaterally at the level of the cricoid. Primary and secondary outcome variables on VFSS were pharyngeal constriction ratio, a validated measure of pharyngeal contractility, and penetration aspiration scale (PAS). A qualitative assessment of lateral neck rotation was performed as a functional measure of neck fibrosis. RESULTS: Simultaneous cervical US and VFSS examinations were performed on 18 patients with a history of radiotherapy for HNCA and on eight controls. The mean (±SD) age of the entire cohort (N = 26) was 66 (±10) years. Individuals with a history of radiation had significantly thinner mean SCMF (0.26 [±0.04 mm]) compared to controls (0.48 [±0.06 mm]; P < .05). Individuals with thinner SCMF were more likely to have moderate to severe restriction in lateral neck rotation, a higher PCR, and a higher PAS (P < .05). CONCLUSION: Thinner sternocleidomastoid fascia on ultrasound in patients having undergone radiotherapy for head and neck cancer was associated with reduced lateral neck movement, poorer pharyngeal constriction and greater penetration/aspiration scale. The data suggest that cervical fibrosis is associated with swallowing dysfunction in head and neck cancer survivors and support the notion that, "As the neck goes, so does the swallow." LEVEL OF EVIDENCE: 3. Laryngoscope, 131:548-552, 2021.

CT-based attenuation correction of whole-body radiotherapy treatment positioning devices in PET/MRI hybrid imaging.

OBJECTIVE: To implement computed tomography (CT)-based attenuation maps of radiotherapy (RT) positioning hardware and radiofrequency (RF) coils to enable hybrid positron emission tomography/magnetic resonance imaging (PET/MRI)-based RT treatment planning. MATERIALS AND METHODS: The RT positioning hardware consisted of a flat RT table overlay, coil holders for abdominal scans, coil holders for head and neck scans and an MRI compatible hip and leg immobilization device. CT images of each hardware element were acquired on a CT scanner. Based on the CT images, attenuation maps of the devices were created. Validation measurements were performed on a PET/MR scanner using a 68Ge phantom (48 MBq, 10 min scan time). Scans with each device in treatment position were performed. Then, reference scans containing only the phantom were taken. The scans were reconstructed online (at the PET/MRI scanner) and offline (via e7tools on a PC) using identical reconstruction parameters. Average reconstructed activity concentrations of the device and reference scans were compared. RESULTS: The device attenuation maps were successfully implemented. The RT positioning devices caused an average decrease of reconstructed PET activity concentration in the range between -8.3 ± 2.1% (mean ± SD) (head and neck coil holder with coils) to -1.0 ± 0.5% (abdominal coil holder). With attenuation correction taking into account RT hardware, these values were reduced to -2.0 ± 1.2% and -0.6 ± 0.5%, respectively. The results of the offline and online reconstructions were nearly identical, with a difference of up to 0.2%. CONCLUSION: The decrease in reconstructed activity concentration caused by the RT positioning devices is clinically relevant and can successfully be corrected using CT-based attenuation maps. Both the offline and online reconstruction methods are viable options.

Radiation eye dose to medical staff during respiratory endoscopy under X-ray fluoroscopy.

Although the clinical value of fluoroscopically guided respiratory endoscopy (bronchoscopy) is clear, there have been very few studies on the radiation dose received by staff during fluoroscopically guided bronchoscopy. The International Commission on Radiological Protection (ICRP) is suggesting reducing the occupational lens dose limit markedly from 150 to 20 mSv/year, averaged over defined periods of five years. The purpose of this study was to clarify the current occupational eye dose of bronchoscopy staff conducting fluoroscopically guided procedures. We measured the occupational eye doses (3-mm-dose equivalent, Hp(3)) of bronchoscopy staff (physicians and nurses) over a 6-month period. The eye doses of eight physicians and three nurses were recorded using a direct eye dosimeter, the DOSIRIS. We also estimated eye doses using personal dosimeters worn at the neck. The mean ± SD radiation eye doses (DOSIRIS) to physicians and nurses were 7.68 ± 5.27 and 2.41 ± 1.94 mSv/6 months, respectively. The new lens dose limit, 20 mSv/year, may be exceeded among bronchoscopy staff, especially physicians. The eye dose of bronchoscopy staff (both physicians and nurses) was underestimated when measured using a neck dosimeter. Hence, the occupational eye dose of bronchoscopy staff should be monitored. To reduce the occupational eye dose, we recommend that staff performing fluoroscopically guided bronchoscopy wear Pb glasses. correct evaluation of the lens dose [Hp(3)] using an eye dosimeter such as the DOSIRIS is necessary for bronchoscopy staff.

Role and limitations of the geometric mean method regarding head rotation in salivary gland scintigraphy: a phantom study.

To investigate the possible influence of head rotation on the results of salivary gland scintigraphy, a phantom study was designed to simulate clinical salivary gland scintigraphy. The quantitative accuracy of regional activity counts was compared for two data acquisition methods involving head rotation: (i) an anterior planar projection-only (ANT) method and (ii) a geometric mean (GM) method using both the anterior and posterior planar projections. The roles and limitations of the GM and ANT methods when used at different head rotation angles were examined. Parallel planar projections of a head phantom with four salivary gland simulators, containing 3.7 MBq 99mTc-sodium pertechnetate, at various rotational settings were acquired using a dual-head gamma camera. The difference between the standard activity counts (no phantom rotation) and the activity counts affected by the phantom rotation was calculated and defined as the rotational bias that decreased the accuracy of activity quantification. For small-angle rotation (≤10°), use of the GM method decreased the bias for all salivary gland simulators. In contrast, the bias of large-angle rotation (>10°) between four salivary gland simulators became conspicuous and complex in both methods. This bias may reflect different attenuation effects caused by displacement of the structures. Our data suggest that the GM method can be used when the head rotation angle is small (≤10°); however, when the head rotation angle is >10°, the non-negligible influence of head rotation should be considered during image acquisition.

Individualized Prophylactic Neck Irradiation in Patients with cN0 Head and Neck Cancer Based on Sentinel Lymph Node(s) Identification: Definitive Results of a Prospective Phase 1-2 Study.

PURPOSE: This prospective, nonrandomized, interventional phase 1-2 study investigated the individualization of elective node irradiation in clinically N0 head and neck squamous cell carcinoma by sentinel lymph node (SLN) mapping with single-photon emission computed tomography/computed tomography (SPECT/CT) and its impact on tumor control and radiation-related toxicity. METHODS AND MATERIALS: Forty-four patients with clinically N0 head and neck squamous cell carcinoma treated with definitive (chemo-)radiation therapy were imaged with SPECT/CT after 99mTc nanocolloid injection around the tumor. The neck levels containing up to the 4 hottest SLNs were selected for prophylactic irradiation. A comparative virtual planning was performed with the selection of neck levels based on the current international guidelines. Regional control was monitored as a function of the selected volume. Dosimetric data for the organs at risk were compared between the plans. Normal tissue complication probability (NTCP) rates were derived for xerostomia, dysphagia, and hypothyroidism to predict the clinical benefit and correlated to quality-of-life (QoL) assessments at 6 months. RESULTS: Sixteen percent of patients presented unpredicted lymphatic drainage, and 48% drained unilaterally. The nodal clinical target volume based on lymphoscintigraphy was smaller than the nodal clinical target volume based on international guidelines by a factor of 2 (P < .0001). After a median follow-up of 46 months, only 1 patient experienced a regional relapse in a nonirradiated area. Significant median dose reductions to organs at risk were observed, particularly to contralateral salivary glands in patients with unilateral drainage (14.6-28.1 Gy) and to the thyroid gland in all patients (22.4-48.9 Gy). Median NTCP reductions were observed for xerostomia (0.3% to 13.7%), dysphagia (1.7% to 10.8%), and hypothyroidism (14.0% to 36.1%). QoL at 6 months was improved, particularly in patients irradiated unilaterally. CONCLUSIONS: Neck SLN mapping with SPECT/CT individualizes and reduces the elective nodal target volumes without compromising the regional control. The NTCP rates were reduced and favorable QoL were observed in all patients, particularly in the case of unilateral irradiation.

Systematic review and meta-analysis of safety and efficacy of high-intensity focused ultrasound (HIFU) for face and neck rejuvenation.

High-intensity focused ultrasound (HIFU) is widely used for skin rejuvenation and tightening. The aim of this study was to determine the safety and efficacy of HIFU for face and neck rejuvenation. A systematic search of peer reviewed articles published before December 2017 was performed using Medline, Web of Science, and Scopus databases. Retrieved studies were screened, and clinical trials or follow-up studies which were evaluated the effect of HIFU on rejuvenation treatments of face and neck area were included. Risk of bias for each study was assessed and was reported. Safety and efficacy variables, which were reported more often in papers, were included in meta-analysis. Seventeen studies involving 477 participants were included in the analysis. Meta-analysis showed moderate improvement as scores of 2.74 (95% CI 2.06-3.43) and 2.68 (95% CI 1.92-3.45), out of 5 maximum score, for objective improvement score and subjective satisfaction score, respectively. Meta-analysis of mean pain score, assessed by a 0-10 Likert score, was 4.2 (95% CI 4.27-5.19). Edema and erythema showed considerable heterogeneity, and no hyperpigmentation was reported by included studies. Included studies used multiple and different outcome variables with different scoring at various time points. Long follow-up was not reported by majority of studies. HIFU is safe procedure in short term and has a moderate effect on rejuvenation of face and neck areas.

Face and neck rejuvenation using an improved non-ablative fractional high power 1064-nm Q-switched Nd:YAG Laser: clinical results in 16 women.

OBJECTIVE: To evaluate the safety and efficacy of a specific treatment protocol using a new and improved non-ablative fractional high-power 1064-nm Q-switched Nd:YAG laser for face and neck rejuvenation. METHODS: Sixteen women, aged 30 to 60 years old, were selected to undergo three consecutive treatment sessions with this new laser at maximum energy (2,400 mJ/pulse, Clear Lift laser®-Harmony XL-Pro, Alma Lasers Ltd.). Face and neck were treated in eight patients, respectively. Each treatment used the same protocol. The efficacy was evaluated by the therapist (TS), the patient (PS), and two separate independent experts who were blind to the study (E1 and E2). RESULTS: According to E1 and E2, the mean reduction in signs of skin aging on a Global Esthetic Improvement Scale was 30-40%. Using a 0-10 points scale, TS and PS mean (range) satisfaction rates were 9.0 (8-10); 9.2 (6-10) for the face and 8.7 (8-10); 8.0 (3-10), for the neck, respectively. The procedure was practically painless, no significant adverse effects were observed, and the patients returned to their daily and work activities without downtime. CONCLUSION: This laser was safe and effective for face and neck minimally invasive rejuvenation, with excellent results using our usual routine use conditions.

Radiomics signature for prediction of lateral lymph node metastasis in conventional papillary thyroid carcinoma.

PURPOSE: Preoperative neck ultrasound (US) for lateral cervical lymph nodes is recommended for all patients undergoing thyroidectomy for thyroid malignancy, but it is operator dependent. We aimed to develop a radiomics signature using US images of the primary tumor to preoperatively predict lateral lymph node metastasis (LNM) in patients with conventional papillary thyroid carcinoma (cPTC). METHODS: Four hundred consecutive cPTC patients from January 2004 to February 2006 were enrolled as the training cohort, and 368 consecutive cPTC patients from March 2006 to February 2007 served as the validation cohort. A radiomics signature, which consisted of 14 selected features, was generated by the least absolute shrinkage and selection operator (LASSO) regression model in the training cohort. The discriminating performance of the radiomics signature was assessed in the validation cohort with the area under the receiver operating characteristic curve (AUC). RESULTS: The radiomics signature was significantly associated with lateral cervical lymph node status (p < 0.001). The AUC of its performance in discriminating metastatic and non-metastatic lateral cervical lymph nodes was 0.710 (95% CI: 0.649-0.770) in the training cohort and was 0.621 (95% CI: 0.560-0.682) in the validation cohort. CONCLUSIONS: The present study showed that US radiomic features of the primary tumor were associated with lateral cervical lymph node status. Although their discriminatory performance was slightly lower in the validation cohort, our study shows that US radiomic features of the primary tumor alone have the potential to predict lateral LNM.

Pharyngeal-sparing radiation for head and neck carcinoma of unknown primary following TORS assisted work-up.

OBJECTIVE: In patients with head and neck carcinoma of unknown primary (HNCUP;pT0) following TORS-assisted workup, we have adopted a pharyngeal-sparing radiation therapy (PSRT) approach targeting only the at-risk neck and omitting treatment of the pharynx. We report outcomes following PSRT, and compare to institutional historical control subjects who received pharyngeal-targeted RT (PRT). METHODS: Between 2009 and 2018, 172 patients underwent TORS-assisted endoscopy as part of their workup for HNCUP. Following TORS, 54 patients had pT0 disease, of which 45 received RT. Forty-nine percent received PSRT and 51% received PRT. RESULTS: No statistically significant differences existed between the PSRT and PRT groups with respect to overall nodal distribution, p16 positivity (55% vs. 43%, P = .12), neck dissection rates (77% vs. 65%, P = .51), and administration of chemotherapy (55% vs. 65%, P = .55). Median follow-up for PSRT and PRT groups were 24 and 28 months, respectively (P = .04). Two-year RFS was 86% and 74% for PSRT and PRT patients, respectively (log-rank P = .30). Three and six patients recurred after PSRT and PRT, respectively. Two-year OS for PSRT and PRT patients was 91% and 74%, respectively (log-rank P = .31). Compared to PRT, PSRT was associated with statistically significantly less: grade 2+ mucositis (18% vs. 91%, P < .01), new opioid requirement (27% vs. 91%, P < .01), mean weight loss during RT (6.2 lbs vs. 17.4 lbs, P < .01), feeding tube placement during RT (5% vs. 43%, P < .01), and treatment-related unplanned hospitalizations (9% vs. 39%, P = .04). CONCLUSION: Following TORS-assisted management of patients with pT0 HNCUP, we observed reduced toxicity following PSRT compared to PRT without apparent compromise of disease cure. LEVEL OF EVIDENCE: Level 3 evidence, retrospective review comparing cases and controls Laryngoscope, 130:691-697, 2020.

MRIgRT head and neck anthropomorphic QA phantom: Design, development, reproducibility, and feasibility study.

PURPOSE: The purpose of this paper was to design, manufacture, and evaluate a tissue equivalent, dual magnetic resonance/computed tomography (MR/CT) visible anthropomorphic head and neck (H&N) phantom. This phantom was specially designed as an end-to-end quality assurance (QA) tool for MR imaging guided radiotherapy (MRIgRT) systems participating in NCI-sponsored clinical trials. METHOD: The MRIgRT H&N phantom was constructed using a water-fillable acrylic shell and a custom insert that mimics an organ at risk (OAR) and target structures. The insert consists of a primary and secondary planning target volume (PTV) manufactured of a synthetic Clear Ballistic gel, an acrylic OAR and surrounding tissue fabricated using melted Superflab. Radiochromic EBT3 film and thermoluminescent detectors (TLDs) were used to measure the dose distribution and absolute dose, respectively. The phantom was evaluated by conducting an end-to-end test that included: imaging on a GE Lightspeed CT simulator, planning on Monaco treatment planning software (TPS), verifying treatment setup with MR, and irradiating on Elekta's 1.5 T Unity MR linac system. The phantom was irradiated three times using the same plan to determine reproducibility. Three institutions, equipped with either ViewRay MRIdian 60 Co or ViewRay MRIdian Linac, were used to conduct a feasibility study by performing independent end-to-end studies. Thermoluminescent detectors were evaluated in both reproducibility and feasibility studies by comparing ratios of measured TLD to reported TPS calculated values. Radiochromic film was used to compare measured planar dose distributions to expected TPS distributions. Film was evaluated by using an in-house gamma analysis software to measure the discrepancies between film and TPS. RESULTS: The MRIgRT H&N phantom on the Unity system resulted in reproducible TLD doses (SD < 1.5%). The measured TLD to calculated dose ratios for the Unity system ranged from 0.94 to 0.98. The Viewray dose result comparisons had a larger range (0.95-1.03) but these depended on the TPS dose calculations from each site. Using a 7%/4 mm gamma analysis, Viewray institutions had average axial and sagittal passing rates of 97.3% and 96.2% and the Unity system had average passing rates of 97.8% and 89.7%, respectively. All of the results were within the Imaging and Radiation Oncology Core in Houston (IROC-Houston) standard credentialing criteria of 7% on TLDs, and >85% of pixels passing gamma analysis using 7%/4 mm on films. CONCLUSIONS: An MRIgRT H&N phantom that is tissue equivalent and visible on both CT and MR was developed. The results from initial reproducibility and feasibility testing of the MRIgRT H&N phantom using the tested MGIgRT systems suggests the phantom's potential utility as a credentialing tool for NCI-clinical trials.

Fractionated head and neck irradiation impacts taste progenitors, differentiated taste cells, and Wnt/ß-catenin signaling in adult mice.

Head and neck cancer patients receiving conventional repeated, low dose radiotherapy (fractionated IR) suffer from taste dysfunction that can persist for months and often years after treatment. To understand the mechanisms underlying functional taste loss, we established a fractionated IR mouse model to characterize how taste buds are affected. Following fractionated IR, we found as in our previous study using single dose IR, taste progenitor proliferation was reduced and progenitor cell number declined, leading to interruption in the supply of new taste receptor cells to taste buds. However, in contrast to a single dose of IR, we did not encounter increased progenitor cell death in response to fractionated IR. Instead, fractionated IR induced death of cells within taste buds. Overall, taste buds were smaller and fewer following fractionated IR, and contained fewer differentiated cells. In response to fractionated IR, expression of Wnt pathway genes, Ctnnb1, Tcf7, Lef1 and Lgr5 were reduced concomitantly with reduced progenitor proliferation. However, recovery of Wnt signaling post-IR lagged behind proliferative recovery. Overall, our data suggest carefully timed, local activation of Wnt/ß-catenin signaling may mitigate radiation injury and/or speed recovery of taste cell renewal following fractionated IR.