Hazards of sparing the ipsilateral parotid gland in the node-positive neck with intensity modulated radiation therapy: Spatial analysis of regional recurrence risk.

PURPOSE: The practice of deliberately sparing the ipsilateral parotid gland with intensity modulated radiation therapy (IMRT) in patients with node-positive head and neck cancer is controversial. We sought to compare the clinical outcomes among consecutive cohorts of patients with head and neck cancer who were treated with differing strategies to spare the parotid gland that is ipsilateral to the involved neck using IMRT. METHODS AND MATERIALS: A total of 305 patients were treated with IMRT for node-positive squamous cell carcinoma of the head and neck. The first 139 patients were treated with IMRT whereby the ipsilateral parotid gland was delineated and intentionally designated as an avoidance structure during planning. The subsequent 166 patients were treated by IMRT without the deliberate sparing of the ipsilateral parotid gland. RESULTS: The 2-year estimates of overall survival, local-regional control, and distant metastasis-free survival were 84%, 73%, and 87%, respectively. The 2-year estimates of overall survival were 77% and 86% among patients who were treated by IMRT with and without the sparing of the ipsilateral parotid gland, respectively (P = .01). The respective rates of 2-year regional control were 76% and 90% (P < .001). A trend was observed between increased nodal burden in the ipsilateral cervical neck and the likelihood of regional failure for both groups. A spatial evaluation revealed a significantly higher incidence of marginal failures and true misses in the cohort of patients who underwent IMRT with the sparing of the ipsilateral parotid gland. CONCLUSION: Caution is urged when using IMRT to spare patients' parotid gland on the involved side of neck disease. Our study showed a significantly higher preponderance of regional failure, which highlights the need for careful patient selection and consideration of clinical and pathological factors that influence the likelihood of disease recurrence in the ipsilateral neck.

Effect of psychosocial distress on outcome for head and neck cancer patients undergoing radiation.

OBJECTIVES/HYPOTHESIS: To determine the impact of pretreatment psychosocial distress on compliance to radiation therapy (RT) and clinical outcomes for patients with head and neck cancer STUDY DESIGN: Self-reported responses to the mood and anxiety domains of the University of Washington Quality of Life instrument were reviewed among 133 patients with newly diagnosed head and neck cancer prior to initiating RT. METHODS: Varying definitions were used (total number of unexpectedly missed RT days, >5 days continuous interruption of RT outside of weekends, >10 days continuous interruption of RT, and failure to complete prescribed course of RT) to analyze the effect of psychosocial disruption on compliance. Survival was determined using the Kaplan-Meier method. RESULTS: The prevalence of pretreatment depression and anxiety was 23% and 47%, respectively. Continuous RT breaks >5 days occurred in 46%, 33%, 10%, 9%, and 0% of patients whose mood was rated as "extremely depressed," "somewhat depressed," "neither in a good mood or depressed," "generally good," and "excellent," respectively (P = .0016). The corresponding proportion of patients who did not complete their planned RT was 23%, 11%, 5%, and 3%, and 0%, respectively (P = .043). The 2-year overall survival of patients who were "extremely depressed" or "somewhat depressed" at baseline was 71% versus 86% for all others (P = .026). Depression was independently associated with decreased overall survival on logistical regression analysis. CONCLUSIONS: Pretreatment depression predicted for decreased RT compliance and inferior survival for head and neck cancer. Additional research to overcome potential barriers to treatment in this setting may be warranted. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:641-645, 2018.

Oropharynx-directed ipsilateral irradiation for p16-positive squamous cell carcinoma involving the cervical lymph nodes of unknown primary origin.

BACKGROUND: The purpose of this study was to present our findings on the use of limited-field, oropharynx-directed ipsilateral irradiation for p16-positive squamous cell carcinoma of unknown primary origin. METHODS: Between April 2011 and January 2016, 25 patients with a histological diagnosis of p16-positive squamous cell carcinoma were selectively irradiated to the ipsilateral oropharynx and cervical neck for tumors of unknown primary origin. The dose to the oropharynx ranged from 54-60 Gy (median 60 Gy) in 30-33 fractions. Concurrent cisplatin-based chemotherapy was administered to 8 patients (32%). RESULTS: The actuarial 2-year estimates of locoregional control, progression-free survival, and overall survival were 91%, 87%, and 92%, respectively. One patient failed in the contralateral neck. There was no grade 3 + toxicity in either the acute or late setting. CONCLUSION: Oropharynx-directed, ipsilateral radiation results in disease control that compares favorably with historical controls treated by comprehensive mucosal and bilateral neck radiation.

Tolerance of the Brachial Plexus to High-Dose Reirradiation.

PURPOSE: To study the tolerance of the brachial plexus to high doses of radiation exceeding historically accepted limits by analyzing human subjects treated with reirradiation for recurrent tumors of the head and neck. METHODS AND MATERIALS: Data from 43 patients who were confirmed to have received overlapping dose to the brachial plexus after review of radiation treatment plans from the initial and reirradiation courses were used to model the tolerance of this normal tissue structure. A standardized instrument for symptoms of neuropathy believed to be related to brachial plexus injury was utilized to screen for toxicity. Cumulative dose was calculated by fusing the initial dose distributions onto the reirradiation plan, thereby creating a composite plan via deformable image registration. The median elapsed time from the initial course of radiation therapy to reirradiation was 24 months (range, 3-144 months). RESULTS: The dominant complaints among patients with symptoms were ipsilateral pain (54%), numbness/tingling (31%), and motor weakness and/or difficulty with manual dexterity (15%). The cumulative maximum dose (Dmax) received by the brachial plexus ranged from 60.5 Gy to 150.1 Gy (median, 95.0 Gy). The cumulative mean (Dmean) dose ranged from 20.2 Gy to 111.5 Gy (median, 63.8 Gy). The 1-year freedom from brachial plexus-related neuropathy was 67% and 86% for subjects with a cumulative Dmax greater than and less than 95.0 Gy, respectively (P=.05). The 1-year complication-free rate was 66% and 87%, for those reirradiated within and after 2 years from the initial course, respectively (P=.06). CONCLUSION: The development of brachial plexus-related symptoms was less than expected owing to repair kinetics and to the relatively short survival of the subject population. Time-dose factors were demonstrated to be predictive of complications.

Inadequate target volume delineation and local-regional recurrence after intensity-modulated radiotherapy for human papillomavirus-positive oropharynx cancer.

PURPOSE: To perform a spatial analysis of local-regional recurrences, in relation to quantitative dose distribution, among patients treated by intensity-modulated radiotherapy (IMRT) for human papillomavirus (HPV)-positive oropharyngeal cancer. METHODS AND MATERIALS: The records of 107 consecutive patients who presented for consideration of re-irradiation for local-regional recurrent disease occurring in a previously irradiated field were reviewed. The original IMRT plans were retrieved for those with HPV-positive disease originating from the oropharynx, and deformable image registration was used to fuse the magnetic resonance imaging (MRI) and positron emission tomography (PET) scans obtained at recurrence to the pre-treatment planning computed tomography (CT) dataset. The recurrent tumor volume (Vrecur) was subsequently identified on axial imaging, and the dose of radiation received by Vrecur was then calculated and analyzed using dose-volume histograms. RESULTS: A total of 83 recurrent lesions occurring in 50 oropharyngeal cancer patients were HPV-positive and met inclusion criteria. Using PET-defined Vrecur, thirty-three lesions were classified as in-field recurrences (40%), 35 were marginal misses (41%), and 15 were true misses (18%). Using the MRI-defined Vrecur, thirty-seven lesions were classified as in-field recurrences (45%), 32 were marginal misses (39%), and 14 were true misses (17%). CONCLUSION: A significant proportion of local-regional recurrences from HPV-positive oropharyngeal cancer represented geographical misses which possibly could have been prevented with more meticulous attention to IMRT planning. This finding has important implications with respect to ongoing attempts to de-escalate radiation dose for this disease. Our data highlight the importance of robust quality assurance with careful review of target volumes prior to the initiation of IMRT.