Long-term outcomes of modern multidisciplinary management of sinonasal cancers: The M. D. Anderson experience.

PURPOSE: To report long-term outcomes of modern radiotherapy for sinonasal cancers. METHODS AND MATERIALS: A retrospective analysis of patients with sinonasal tumors treated with intensity-modulated radiotherapy or proton therapy. Multivariate analysis was used to determine predictive variables of progression free survival (PFS) and overall survival (OS). RESULTS: Three hundred and eleven patients were included, with median follow-up of 75 months. The most common histologies were squamous cell (42%), adenoid cystic (15%), and sinonasal undifferentiated carcinoma (15%). Induction chemotherapy was administered to 47% of patients; 68% had adjuvant radiotherapy. Ten-year local control, regional control, distant metastasis free survival, PFS, and overall survival rates were 73%, 88%, 47%, 32%, and 51%, respectively. Age, non-nasal cavity tumor site, T3-4 stage, neck dissection, and radiation dose were predictive of PFS, while age, non-nasal cavity tumor site, T3-4 stage, positive margins, neck dissection, and use of neoadjuvant chemotherapy were predictive of OS. There was a 13% rate of late grade ≥3 toxicities. CONCLUSION: This cohort of patients with sinonasal cancer treated with modern radiotherapy demonstrates favorable disease control rate and acceptable toxicity profile.

Stereotactic body ablative radiotherapy for reirradiation of small volume head and neck cancers is associated with prolonged survival: Large, single-institution, modern cohort study.

BACKGROUND: Recurrent head and neck cancer has poor prognosis. Stereotactic body radiotherapy (SBRT) may improve outcomes by delivering ablative radiation doses. METHODS: We reviewed patients who received definitive-intent SBRT reirradiation at our institution from 2013 to 2020. Patterns of failure, overall survival (OS), and toxicities were analyzed. RESULTS: One hundred and thirty-seven patients were evaluated. The median OS was 44.3 months. The median SBRT dose was 45 Gy and median target volume 16.9 cc. The 1-year local, regional, and distant control was 78%, 66%, and 83%, respectively. Systemic therapy improved regional (p = 0.004) and distant control (p = 0.04) in nonmetastatic patients. Grade 3+ toxicities were more common at mucosal sites (p = 0.001) and with concurrent systemic therapy (p = 0.02). CONCLUSIONS: In a large cohort of SBRT reirradiation for recurrent, small volume head and neck cancers, a median OS of 44.3 months was observed. Systemic therapy improved regional and distant control. Toxicities were modulated by anatomic site and systemic therapy.

Work Outcomes after Intensity-Modulated Proton Therapy (IMPT) versus Intensity-Modulated Photon Therapy (IMRT) for Oropharyngeal Cancer.

PURPOSE: We compared work outcomes in patients with oropharyngeal cancer (OPC), randomized to intensity-modulated proton (IMPT) versus intensity-modulated photon therapy (IMRT) for chemoradiation therapy (CRT). PATIENTS AND METHODS: In 147 patients with stage II-IVB squamous cell OPC participating in patient-reported outcomes assessments, a prespecified secondary aim of a randomized phase II/III trial of IMPT (n = 69) versus IMRT (n = 78), we compared absenteeism, presenteeism (i.e., the extent to which an employee is not fully functional at work), and work productivity losses. We used the work productivity and activity impairment questionnaire at baseline (pre-CRT), at the end of CRT, and at 6 months, 1 year, and 2 years. A one-sided Cochran-Armitage test was used to analyze within-arm temporal trends, and a χ2 test was used to compare between-arm differences. Among working patients, at each follow-up point, a 1-sided Wilcoxon rank-sum test was used to compare work-productivity scores. RESULTS: Patient characteristics in IMPT versus IMRT arms were similar. In the IMPT arm, within-arm analysis demonstrated that an increasing proportion of patients resumed working after IMPT, from 60% (40 of 67) pre-CRT and 71% (30 of 42) at 1 year to 78% (18 of 23) at 2 years (P = 0.025). In the IMRT arm, the proportion remained stable, with 57% (43 of 76) pre-CRT, 54% (21 of 39) at 1 year, and 52% (13 of 25) working at 2 years (P = 0.47). By 2 years after CRT, the between-arm difference between patients who had IMPT and those who had IMRT trended toward significance (P = 0.06). Regardless of treatment arm, among working patients, the most severe work impairments occurred from treatment initiation to the end of CRT, with significant recovery from absenteeism, presenteeism, and productivity impairments by the 2-year follow-up (P < 0.001 for all). Higher magnitudes of recovery from absenteeism (at 1 year, P = 0.05; and at 2 years, P = 0.04) and composite work impairment scores (at 1 year, P = 0.04; and at 2 years, P = 0.04) were seen in patients treated with IMPT versus those treated with IMRT. CONCLUSION: In patients with OPC receiving curative CRT, patients randomized to IMPT demonstrated increasing work and productivity recovery trends. Studies are needed to identify mechanisms underlying head and neck CRT treatment causing work disability and impairment.

Defining the dose-volume criteria for laryngeal sparing in locally advanced oropharyngeal cancer utilizing split-field IMRT, whole-field IMRT and VMAT.

PURPOSE: To determine the optimal dose-volume constraint for laryngeal sparing using three commonly employed intensity modulated radiation therapy (IMRT) approaches in patients with oropharyngeal cancer treated to the bilateral neck. MATERIALS AND METHODS: Thirty patients with stage II-IVA oropharynx cancers received definitive radiotherapy with split-field IMRT (SF-IMRT) to the bilateral neck between 2008 and 2013. Each case was re-planned using whole-field IMRT (WF-IMRT) and volumetric modulated arc therapy (VMAT) and plan quality metrics and dose to laryngeal structures was evaluated. Two larynx volumes were defined and compared on the current study: the Radiation Therapy Oncology Group (RTOG) larynx as defined per the RTOG 1016 protocol and the MDACC larynx defined as the components of the larynx bounded by the superior and inferior extent of the thyroid cartilage. RESULTS: Target coverage, conformity, and heterogeneity indices were similar in all techniques. The RTOG larynx mean dose was lower with WF-IMRT than SF-IMRT (22.1 vs 25.8 Gy; P < 0.01). The MDACC larynx mean dose was 17.5 Gy ± 5.4 Gy with no differences between the 3 techniques. WF-IMRT and VMAT plans were associated with lower mean doses to the supraglottic larynx (42.1 vs 41.2 vs 54.8 Gy; P < 0.01) and esophagus (18.1 vs 18.2 vs 36 Gy; P < 0.01). CONCLUSIONS: Modern whole field techniques can provide effective laryngeal sparing in patients receiving radiotherapy to the bilateral neck for advanced oropharyngeal cancers. SUMMARY: We evaluated laryngeal dose in patients with locally advanced oropharyngeal cancer treated to the bilateral neck using split-field IMRT (SF-IMRT), whole-field IMRT (WF-IMRT) and volumetric arc therapy (VMAT). All three techniques provided good sparing of laryngeal structures and were able to achieve a mean larynx dose < 33 Gy. There were no significant differences in dose to target structures or non-laryngeal organs at risk among techniques.

Neurologic sequelae following radiation with and without chemotherapy for oropharyngeal cancer: Patient reported outcomes study.

BACKGROUND: There is little data describing neurocognitive late sequelae in patients treated for oropharyngeal cancer. METHODS: Using PROs, scores for "numbness/tingling" and "difficulty remembering" were assessed. Wilcoxon testing was utilized to compare mean assessment scores (1-10) between treatment subgroups. RESULTS: Four-hundred ninety-seven patients were evaluated and 267 (54%) received chemotherapy. The mean score for numbness/tingling for patients receiving radiation alone was 0.99 and for each chemotherapy subgroup were: Induction chemotherapy (IC), 1.35 (n = 99); concurrent chemotherapy (CCRT), 1.04 (n = 111) and IC + CCRT, 2.48 (n = 57); 30% of patients who received IC + CCRT had scores ≥5. The mean scores for difficulty remembering were XRT: 1.44, chemotherapy: 1.45, and IC + CCRT subgroup: 2.42. CONCLUSIONS: The symptom burden related to peripheral neuropathy and cognitive complaints was minimal. A minority of patients reported high burdens. Particularly, 30% of patients receiving IC + CCRT described moderate to severe numbness/tingling.

Long-term quality of life after definitive treatment of sinonasal and nasopharyngeal malignancies.

OBJECTIVE: To evaluate long-term global and site-specific health-related quality of life (HRQoL) in patients treated for sinonasal and nasopharyngeal malignancies. STUDY DESIGN: Cross-sectional. METHODS: One hundred fourteen patients with sinonasal and nasopharyngeal malignancies received surgery, radiation, systemic chemotherapy, or a combination thereof, with curative intent. Validated global ([EuroQol-5D] Visual Analogue Scale [EQ-5D VAS]) and disease-specific instruments (MD Anderson Symptom Inventory-Head and Neck [MDASI-HN], Anterior Skull Base Questionnaire [ASBQ]) were administered to patients who were both free of disease and had completed treatment at least 12 months previously. Associations between instruments, instrument domains, and specific clinical parameters were analyzed. RESULTS: The median age was 55 years. The mean EQ-5D VAS, MDASI-22 composite score, and ASBQ score were 74 (standard deviation [SD] 21), 48 (SD 36), and 130 (SD 27), respectively. The most frequently reported high-severity items in MDASI-HN were dry mouth and difficulty tasting food. The most frequently reported high-severity items in ASBQ were difficulty with smell and nasal secretions. Advanced Tumor (T) classification was associated with worse overall ASBQ sum score (P = 0.02). ASBQ performance at home and MDASI-HN drowsy symptom items independently predicted worse global HRQoL as measured by the EQ-5D VAS (P < 0.001). CONCLUSION: Global HRQoL for survivors of sinonasal and nasopharyngeal malignancies after multimodality treatment approximates that of the U.S. population for the same age group. ASBQ and MDASI-HN correlate well with global HRQoL outcomes as measured by EQ-5D VAS. MDASI-HN and ASBQ elicited unique symptoms, highlighting the complex symptom burden experienced by these patients. Further studies should identify patients predisposed to reduced long-term QOL. LEVEL OF EVIDENCE: 3 Laryngoscope, 130:86-93, 2020.

Evaluation of the accuracy of deformable image registration on MRI with a physical phantom.

BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) has gained popularity in radiation therapy simulation because it provides superior soft tissue contrast, which facilitates more accurate target delineation compared with computed tomography (CT) and does not expose the patient to ionizing radiation. However, image registration errors in commercial software have not been widely reported. Here we evaluated the accuracy of deformable image registration (DIR) by using a physical phantom for MRI. METHODS AND MATERIALS: We used the "Wuphantom" for end-to-end testing of DIR accuracy for MRI. This acrylic phantom is filled with water and includes several fillable inserts to simulate various tissue shapes and properties. Deformations and changes in anatomic locations are simulated by changing the rotations of the phantom and inserts. We used Varian Velocity DIR software (v4.0) and CT (head and neck protocol) and MR (T1- and T2-weighted head protocol) images to test DIR accuracy between image modalities (MRI vs CT) and within the same image modality (MRI vs MRI) in 11 rotation deformation scenarios. Large inserts filled with Mobil DTE oil were used to simulate fatty tissue, and small inserts filled with agarose gel were used to simulate tissues slightly denser than water (e.g., prostate). Contours of all inserts were generated before DIR to provide a baseline for contour size and shape. DIR was done with the MR Correctable Deformable DIR method, and all deformed contours were compared with the original contours. The Dice similarity coefficient (DSC) and mean distance to agreement (MDA) were used to quantitatively validate DIR accuracy. We also used large and small regions of interest (ROIs) during between-modality DIR tests to simulate validation of DIR accuracy for organs at risk (OARs) and propagation of individual clinical target volume (CTV) contours. RESULTS: No significant differences in DIR accuracy were found for T1:T1 and T2:T2 comparisons (P > 0.05). DIR was less accurate for between-modality comparisons than for same-modality comparisons, and was less accurate for T1 vs CT than for T2 vs CT (P < 0.001). For between-modality comparisons, use of a small ROI improved DIR accuracy for both T1 and T2 images. CONCLUSION: The simple design of the Wuphantom allows seamless testing of DIR; here we validated the accuracy of MRI DIR in end-to-end testing. T2 images had superior DIR accuracy compared with T1 images. Use of small ROIs improves DIR accuracy for target contour propagation.

A prospective evaluation of health-related quality of life after skull base re-irradiation.

PURPOSE: To report cancer control outcomes and health-related quality of life (HRQoL) outcomes after highly conformal skull-based re-irradiation (re-RT). METHODS: Patients planned for curative intent re-RT to a recurrent or new skull base tumor were enrolled. HRQoL were assessed using the MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) and the anterior skull base surgery quality of life (ASBQ) questionnaires. RESULTS: Thirty-nine patients were treated with stereotactic body RT or intensity modulated RT. Median follow-up was 14 months. Progression free survival was 71% at 1-year. There was mild clinically significant worsening of fatigue, lack of appetite and drowsiness (MDASI-BT), and physical function (ASBQ) at the end of RT, followed by recovery to baseline on subsequent follow-ups. Subjective emotions were clinically improved at 12 months, with patients reporting feeling less tense/nervous. CONCLUSION: Conformal skull base re-RT is associated with mild immediate deterioration in physical function followed by rapid and sustained recovery.

Quantifying the accuracy of deformable image registration for cone-beam computed tomography with a physical phantom.

PURPOSE: Kilo-voltage cone-beam computed tomography (CBCT) is widely used for patient alignment, contour propagation, and adaptive treatment planning in radiation therapy. In this study, we evaluated the accuracy of deformable image registration (DIR) for CBCT under various imaging protocols with different noise and patient dose levels. METHODS: A physical phantom previously developed to facilitate end-to-end testing of the DIR accuracy was used with Varian Velocity v4.0 software to evaluate the performance of image registration from CT to CT, CBCT to CT, and CBCT to CBCT. The phantom is acrylic and includes several inserts that simulate different tissue shapes and properties. Deformations and anatomic changes were simulated by changing the rotations of both the phantom and the inserts. CT images (from a head and neck protocol) and CBCT images (from pelvis, head and "Image Gently" protocols) were obtained with different image noise and dose levels. Large inserts were filled with Mobil DTE oil to simulate soft tissue, and small inserts were filled with bone materials. All inserts were contoured before the DIR process to provide a ground truth contour size and shape for comparison. After the DIR process, all deformed contours were compared with the originals using Dice similarity coefficient (DSC) and mean distance to agreement (MDA). Both large and small volume of interests (VOIs) for DIR volume selection were tested by simulating a DIR process that included whole patient image volume and clinical target volumes (CTV) only (for CTVs propagation). RESULTS: For cross-modality DIR registration (CT to CBCT), the DSC were >0.8 and the MDA were <3 mm for CBCT pelvis, and CBCT head protocols. For CBCT to CBCT and CT to CT, the DIR accuracy was improved relative to the cross-modality tests. For smaller VOIs, the DSC were >0.8 and MDA <2 mm for all modalities. CONCLUSIONS: The accuracy of DIR depends on the quality of the CBCT image at different dose and noise levels.

Prospective quantitative quality assurance and deformation estimation of MRI-CT image registration in simulation of head and neck radiotherapy patients.

BACKGROUND: MRI-guided radiotherapy planning (MRIgRT) may be superior to CT-guided planning in some instances owing to its improved soft tissue contrast. However, MR images do not communicate tissue electron density information necessary for dose calculation and therefore must either be co-registered to CT or algorithmically converted to synthetic CT. No robust quality assessment of commercially available MR-CT registration algorithms is yet available; thus we sought to quantify MR-CT registration formally. METHODS: Head and neck non-contrast CT and T2 MRI scans acquired with standard treatment immobilization techniques were prospectively acquired from 15 patients. Per scan, 35 anatomic regions of interest (ROIs) were manually segmented. MRIs were registered to CT rigidly (RIR) and by three commercially available deformable registration algorithms (DIR). Dice similarity coefficient (DSC), Hausdorff distance mean (HD mean) and Hausdorff distance max (HD max) metrics were calculated to assess concordance between MRI and CT segmentations. Each DIR algorithm was compared to DIR using the nonparametric Steel test with control for individual ROIs (n = 105 tests) and for all ROIs in aggregate (n = 3 tests). The influence of tissue type on registration fidelity was assessed using nonparametric Wilcoxon pairwise tests between ROIs grouped by tissue type (n = 12 tests). Bonferroni corrections were applied for multiple comparisons. RESULTS: No DIR algorithm improved the segmentation quality over RIR for any ROI nor all ROIs in aggregate (all p values >0.05). Muscle and gland ROIs were significantly more concordant than vessel and bone, but DIR remained non-different from RIR. CONCLUSIONS: For MR-CT co-registration, our results question the utility and applicability of commercially available DIR over RIR alone. The poor overall performance also questions the feasibility of translating tissue electron density information to MRI by CT registration, rather than addressing this need with synthetic CT generation or bulk-density assignment.

Intensity modulated proton therapy (IMPT) - The future of IMRT for head and neck cancer.

Radiation therapy plays an integral role in the management of head and neck cancers (HNCs). While most HNC patients have historically been treated with photon-based radiation techniques such as intensity modulated radiation therapy (IMRT), there is a growing awareness of the potential clinical benefits of proton therapy over IMRT in the definitive, postoperative and reirradiation settings given the unique physical properties of protons. Intensity modulated proton therapy (IMPT), also known as "pencil beam proton therapy," is a sophisticated mode of proton therapy that is analogous to IMRT and an active area of investigation in cancer care. Multifield optimization IMPT allows for high quality plans that can target superficially located HNCs as well as large neck volumes while significantly reducing integral doses. Several dosimetric studies have demonstrated the superiority of IMPT over IMRT to improve dose sparing of nearby organs such as the larynx, salivary glands, and esophagus. Evidence of the clinical translation of these dosimetric advantages has been demonstrated with documented toxicity reductions (such as decreased feeding tube dependency) after IMPT for patients with HNCs. While there are relative challenges to IMPT planning that exist today such as particle range uncertainties and high sensitivity to anatomical changes, ongoing investigations in image-guidance techniques and robust optimization methods are promising. A systematic approach towards utilizing IMPT and additional prospective studies are necessary in order to more accurately estimate the clinical benefit of IMPT over IMRT and passive proton therapy on a case-by-case basis for patients with sub-site specific HNCs.

Optimizing laryngeal sparing with intensity modulated radiotherapy or volumetric modulated arc therapy for unilateral tonsil cancer.

BACKGROUND AND PURPOSE: Minimizing radiation dose exposure to nearby organs is key to limiting clinical toxicities associated with radiotherapy. Several treatment modalities such as split- or whole-field intensity-modulated radiotherapy (SF-IMRT, WF-IMRT) and volumetric modulated arc therapy (VMAT) are being used to treat tonsillar cancer patients with unilateral neck radiotherapy. Herein, we provide a modern dosimetric comparison of all three techniques. MATERIALS AND METHODS: Forty patients with tonsillar cancer treated with definitive, ipsilateral neck SF-IMRT were evaluated. Each patient was re-planned with WF-IMRT and VMAT techniques, and doses to selected organs-at-risk (OARs) including the larynx, esophagus, and brainstem were compared. RESULTS: No significant differences in target coverage existed between plans; however, the heterogeneity index improved using WF-IMRT and VMAT relative to SF-IMRT. Compared to SF-IMRT, WF-IMRT and VMAT plans had significantly lower mean doses to the supraglottic larynx (31 Gy, 18.5 Gy, 17 Gy; p < 0.01), the MDACC-defined larynx (13.4 Gy, 10.5 Gy, 9.8 Gy; p < 0.01), and RTOG-defined larynx (15.8 Gy, 12.1 Gy, 11.1 Gy; p < 0.01), respectively. Mean esophageal dose was lowest with SF-IMRT over WF-IMRT and VMAT (5.9 Gy, 12.2 Gy, 11.1 Gy; p < 0.01) but only in the absence of lower neck disease. On average, VMAT plans had shorter treatment times and required less monitor units than both SF-IMRT and WF-IMRT. CONCLUSION: In the setting of unilateral neck radiotherapy, WF-IMRT and VMAT plans can be optimized to significantly improve dose sparing of critical structures compared to SF-IMRT. VMAT offers additional advantages of shorter treatment times and fewer required monitor units.

Two-year prevalence of dysphagia and related outcomes in head and neck cancer survivors: An updated SEER-Medicare analysis.

BACKGROUND: The aim of the study was to examine prevalence of dysphagia at the population level in head and neck cancer (HNC) survivors. METHODS: Surveillance, Epidemiology, and End Results-Medicare claims among 16 194 patients with HNC (2002-2011) were analyzed to estimate 2-year prevalence of dysphagia, stricture, and aspiration pneumonia, and derive treatment- and site-specific estimates. RESULTS: Prevalence of dysphagia, stricture, pneumonia, and aspiration pneumonia was 45.3% (95% confidence interval [CI]: 44.5-46.1), 10.2% (95% CI: 9.7-10.7), 26.3% (95% CI: 25.6-26.9), and 8.6% (95% CI: 8.2-9.1), respectively. Dysphagia increased by 11.7% over the 10-year period (P < .001). Prevalence was highest after chemoradiation and multimodality therapy. CONCLUSION: Comparing to published rates using similar methodology the preceding decade (1992-1999), prevalence of dysphagia based on claims data was similar in 2002-2011 in this study. These results suggest persistence of dysphagia as a highly prevalent morbidity, even in the decade in which highly conformal radiotherapy and minimally invasive surgeries were popularized.

Magnetic Resonance-based Response Assessment and Dose Adaptation in Human Papilloma Virus Positive Tumors of the Oropharynx treated with Radiotherapy (MR-ADAPTOR): An R-IDEAL stage 2a-2b/Bayesian phase II trial.

BACKGROUND: Current standard radiotherapy for oropharynx cancer (OPC) is associated with high rates of severe toxicities, shown to adversely impact patients' quality of life. Given excellent outcomes of human papilloma virus (HPV)-associated OPC and long-term survival of these typically young patients, treatment de-intensification aimed at improving survivorship while maintaining excellent disease control is now a central concern. The recent implementation of magnetic resonance image - guided radiotherapy (MRgRT) systems allows for individual tumor response assessment during treatment and offers possibility of personalized dose-reduction. In this 2-stage Bayesian phase II study, we propose to examine weekly radiotherapy dose-adaptation based on magnetic resonance imaging (MRI) evaluated tumor response. Individual patient's plan will be designed to optimize dose reduction to organs at risk and minimize locoregional failure probability based on serial MRI during RT. Our primary aim is to assess the non-inferiority of MRgRT dose adaptation for patients with low risk HPV-associated OPC compared to historical control, as measured by Bayesian posterior probability of locoregional control (LRC). METHODS: Patients with T1-2 N0-2b (as per AJCC 7th Edition) HPV-positive OPC, with lymph node <3 cm and <10 pack-year smoking history planned for curative radiotherapy alone to a dose of 70 Gy in 33 fractions will be eligible. All patients will undergo pre-treatment MRI and at least weekly intra-treatment MRI. Patients undergoing MRgRT will have weekly adaptation of high dose planning target volume based on gross tumor volume response. The stage 1 of this study will enroll 15 patients to MRgRT dose adaptation. If LRC at 6 months with MRgRT dose adaptation is found sufficiently safe as per the Bayesian model, stage 2 of the protocol will expand enrollment to an additional 60 patients, randomized to either MRgRT or standard IMRT. DISCUSSION: Multiple methods for safe treatment de-escalation in patients with HPV-positive OPC are currently being studied. By leveraging the ability of advanced MRI techniques to visualize tumor and soft tissues through the course of treatment, this protocol proposes a workflow for safe personalized radiation dose-reduction in good responders with radiosensitive tumors, while ensuring tumoricidal dose to more radioresistant tumors. MRgRT dose adaptation could translate in reduced long term radiation toxicities and improved survivorship while maintaining excellent LRC outcomes in favorable OPC. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03224000; Registration date: 07/21/2017.

Outcomes of oral cavity cancer patients treated with surgery followed by postoperative intensity modulated radiation therapy.

OBJECTIVES: Although treatment paradigms have not changed significantly, radiotherapy, surgery, and imaging techniques have improved, leading us to investigate oncologic and survival outcomes for oral cavity squamous cell cancer (OCSCC) patients treated with surgery followed by postoperative IMRT. MATERIAL AND METHODS: Records of patients with pathological diagnosis of OCSCC treated between 2000 and 2012 were retrospectively reviewed. Patients' demographic, disease, and treatment criteria were extracted. Kaplan-Meier method was used to calculate survival curves. RESULTS: Two hundred eighty-nine patients were analyzed. Median follow-up was 35months. Two hundred sixty-eight had neck dissections (93%), of which 66% had nodal involvement, and 51% of those positive dissections had extracapsular extension. Forty patients received induction chemotherapy and 107 received concurrent chemotherapy. Median dose to high risk clinical target volume was 60Gy/30 fractions. The 5-year locoregional control and overall survival rates were 76% and 57%, respectively. Tumors with >1.5cm depth of invasion had significantly higher risk of local failure compared with ≤1.5cm (p<0.001). In multivariate analysis, positive and no neck dissection (p=0.01), positive lymphovascular invasion (p=0.006) and >1.5cm depth of invasion (p=0.003) were independent predictors of poorer survival. CONCLUSIONS: Disease outcomes were consistent with historical data and did not appear compromised by the use of IMRT.

Patterns of locoregional failure following post-operative intensity-modulated radiotherapy to oral cavity cancer: quantitative spatial and dosimetric analysis using a deformable image registration workflow.

BACKGROUND: We sought to identify spatial/dosimetric patterns of failure for oral cavity cancer patients receiving post-operative IMRT (PO-IMRT). METHODS: Two hundred eighty-nine OCC patients receiving PO-IMRT were retrospectively reviewed from 2000 to 2012. Diagnostic CT documenting recurrence (rCT) was co-registered with planning CT (pCT) using a validated deformable image registration software. Manually segmented recurrent gross disease (rGTV) was deformed to co-registered pCTs. Mapped rGTVs were compared dosimetrically to planned dose and spatially to planning target volumes using centroid-based approaches. Failures types were classified using combined spatial/dosimetric criteria: A (central high-dose), B (peripheral high-dose), C (central intermediate/low-dose), D (peripheral intermediate/low-dose), and E (extraneous-dose). RESULTS: Fifty-four patients with recurrence were analyzed; 26 local recurrence, 19 regional recurrence, and 9 both local and regional recurrence. Median time to recurrence was 4 months (range 0-71). Median rGTVs volume was 3.7 cm3 (IQR 1.4-10.6). For spatial and dosimetric analysis of the patterns of failure, 30 patients (55.5%) were classified as type A (central high-dose). Non-central high dose failures were distributed as follows: 2 (3.7%) type B, 10 (18.5%) type C, 1 (1.8%) type D, and 9 (16.7%) type E. Non-IMRT failure in the matching low-neck field was seen in two patients. No failures were noted at the IMRT-supraclavicular field match-line. CONCLUSIONS: Approximately half of patients with local/regional failure had non-central high dose recurrence. Peripheral high dose misses were uncommon reflecting adequate delineation and dose delivery. Future strategies are needed to reduce types C and E failures.

Clinical outcomes after local field conformal reirradiation of patients with retropharyngeal nodal metastasis.

BACKGROUND: The purpose of this study was to present our experience with retropharyngeal node reirradiation using highly conformal radiotherapy (RT). METHODS: A retrospective screen of 2504 consecutively irradiated patients with head and neck malignancies between 2005 and 2015 identified 19 patients who underwent reirradiation for retropharyngeal node metastasis. Clinical and toxicity outcomes were assessed in these patients. RESULTS: Thirteen patients (68%) had squamous cell carcinoma. Eleven patients (58%) received conventionally fractionated intensity-modulated radiotherapy (IMRT) or proton therapy, and 8 patients (42%) received single-fractionated or hypofractionated stereotactic RT. Fourteen patients (74%) received chemotherapy. Median follow-up was 14.7 months. The 1-year local control, locoregional control, overall survival, and progression-free survival rates were 100%, 94%, 92%, and 92%, respectively. Three patients (16%) experienced acute grade 3 toxicity and occurred in those treated with IMRT. There was no late grade ≥3 toxicity. CONCLUSION: Retropharyngeal node reirradiation with conformal therapy is well tolerated and associated with excellent short-term disease control.

Delayed lower cranial neuropathy after oropharyngeal intensity-modulated radiotherapy: A cohort analysis and literature review.

BACKGROUND: The purpose of this study was to examine swallowing-related lower cranial nerve palsy (LCNP) in oropharyngeal cancer (OPC) survivors after intensity-modulated radiotherapy (IMRT). METHODS: Patients treated with definitive IMRT (66-72 Gy) were pooled from institutional trial databases. Prospective analyses on parent trials included videofluoroscopy, clinical LCNP examination, and questionnaires pre-IMRT, 6 months post-IMRT, 12 months post-IMRT, and 24 months post-IMRT. Time-to-event and incidence of LCNP was estimated with competing risk methods. Literature review (1977-2015) summarized published LCNP outcomes. RESULTS: Three of 59 oropharyngeal cancer survivors with a minimum 2-year follow-up developed hypoglossal palsy ipsilateral to the index tumor (median latency 6.7 years; range 4.6-7.6 years). At a median of 5.7 years, cumulative incidence of LCNP was 5%. LCNP preceded progressive dysphagia in all cases. Published studies found median incidence of radiation-associated LCNP was 10.5% after NPC, but no OPC cancer-specific estimate. CONCLUSION: Although uncommon, the potential for late LCNP preceding swallowing deterioration highlights the importance of long-term functional surveillance in OPC survivorship.

Cohort study of oncologic emergencies in patients with head and neck cancer.

BACKGROUND: Treatments for head and neck squamous cell carcinoma (HNSCC) are associated with toxicities that lead to emergency department presentation. METHODS: We utilized data from an ongoing prospective cohort of newly diagnosed, previously untreated patients (N = 298) with HNSCC to evaluate the association between clinical and epidemiologic factors and risk for and frequency of emergency department presentation. Time to event was calculated from the date of treatment initiation to emergency department presentation, date of death, or current date. Frequency of emergency department presentation was the sum of emergency department visits during the follow-up time. RESULTS: History of hypertension, normal/underweight body mass index (BMI), and probable depression predicted increased risk for emergency department presentation. BMI and severe pain were associated with higher frequency of emergency department presentations. CONCLUSION: Clinical and epidemiologic factors can help predict patients with HNSCC who will present to the emergency department. Such knowledge may improve treatment-related patient outcomes and quality of life. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1195-1204, 2017.

Intensity-Modulated Proton Therapy Adaptive Planning for Patients with Oropharyngeal Cancer.

PURPOSE: The authors aimed to illustrate the potential dose differences to clinical target volumes (CTVs) and organs-at-risk (OARs) volumes after proton adaptive treatment planning was used. PATIENTS AND METHODS: The records of 10 patients with oropharyngeal cancer were retrospectively reviewed. Each patient's treatment plan was generated by using the Eclipse treatment planning system. Verification computed tomography (CT) scan was performed during the fourth week of treatment. Deformable image registrations were performed between the 2 CT image sets, and the CTVs and major OARs were transferred to the verification CT images to generate the adaptive plan. We compared the accumulated doses to CTVs and OARs between the original and adaptive plans, as well as between the adaptive and verification plans to simulate doses that would have been delivered if the adaptive plans were not used. RESULTS: Body contours were different on planning and week-4 verification CTs. Mean volumes of all CTVs were reduced by 4% to 8% (P ≤ .04), and the volumes of left and right parotid glands also decreased (by 11% to 12%, P ≤ .004). Brainstem and oral cavity volumes did not significantly differ (all P ≥ .14). All mean doses to the CTV were decreased for up to 7% (P ≤ .04), whereas mean doses to the right parotid and oral cavity increased from a range of 5% to 8% (P ≤ .03), respectively. CONCLUSION: Verification and adaptive planning should be recommended during the course of proton therapy for patients with head and neck cancer to ensure adequate dose deliveries to the planned CTVs, while safe doses to OARs can be respected.