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Objectives/hypothesis To evaluate the long-term disease control, survival, and complications after definitive radiotherapy (RT) alone or combined with adjuvant chemotherapy with or without planned neck dissection for base of tongue squamous cell carcinoma (SCC). Study design We retrospectively reviewed the medical records of 467 patients treated at the University of Florida with definitive RT alone or combined with adjuvant chemotherapy between 1964 and 2011 for base of tongue SCC. Methods Median follow-up was 5.6 years. Median total dose to the primary site was 74.4 Gy. Eighty-seven patients (19%) were treated with once-daily fractionation, and 380 (81%) received altered fractionation schedules. Intensity-modulated RT was used in 128 patients (27%). Chemotherapy was administered to 173 (37%) patients. Planned neck dissection after RT was performed in 226 patients (48%). Data regarding p16 pathway activation were available for 25 patients. Results At 5 years, the local, local-regional, and regional control rates were 85.5%, 80.0%, and 90.0%, respectively. The 5-year overall, cause-specific, and distant metastasis-free survival rates were 59.1%, 71.5%, and 84.1%, respectively. Sixty-four patients (14%) developed one or more severe late complications. Fifty patients (11%) required late gastrostomy tube placement. Conclusions This study supports the continued use of RT alone or combined with adjuvant chemotherapy for patients with base of tongue SCC, as this treatment yields high rates of cause-specific survival and disease control, with a relatively low rate of late complications. Level of evidence 4. Laryngoscope, 127:1589-1594, 2017.

BACKGROUND Oropharyngeal squamous cell carcinoma (SCC) is known for its propensity for aggressive local progression and regional lymphatic spread. Distant metastases are relatively uncommon and the likelihood of hematogenous dissemination is primarily related to the extent and location of cervical lymph node metastases. Common sites of distant metastasis include the liver and lung. METHODS We report an unusual case of base of tongue SCC with infiltrative bone marrow carcinomatosis presenting months after definitive chemoradiation despite locoregional control. RESULTS Our patient exhibited an unusual pattern of distant dissemination after definitive chemoradiation had resulted in locoregional control. CONCLUSION Patients who present with bone marrow failure after definitive treatment with apparent disease control should be monitored for bone marrow infiltration by the tumor and, if such infiltration is present, should be evaluated for palliative chemotherapy. Unfortunately, the prognosis for such patients is poor. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2449-E2453, 2016.

Objective Patients with mucosal squamous cell carcinoma (SCC) of the head and neck almost always have a primary site in the base of tongue or tonsillar fossa. Lingual tonsillectomy has recently been advocated as part of the diagnostic evaluation as opposed to directed biopsies of the base of tongue and thought to possibly result in an increased likelihood or cure. The purpose of this project is to determine whether this is probable. Materials and methods We reviewed the medical records of patients treated with primary radiotherapy (RT) between January 1983 and March 2013. The outcomes were compared following RT in consecutively treated patients with either T1-2 base of tongue or unknown primary (cancer of unknown primary) SCC with predominantly level 2 adenopathy. Results At 10 years, there were no clinically significant differences in the 2 groups, in local control, regional control, freedom from distant metastases, disease-specific, or cause-specific survival. Overall survival at 10 years was improved with T1-2 base of tongue cancers but not for those with T0 N3 disease. The reasons for this are unclear. Conclusions Tongue base biopsy (or lingual tonsillectomy) likely increases the probability of identifying an unknown primary in the base of tongue, but it does not improve outcome following RT for patients with cancer of unknown primary SCC with predominantly level 2 adenopathy.

Purpose To evaluate the long-term effectiveness of radiotherapy (RT) in the treatment of sinonasal undifferentiated carcinoma (SNUC). Materials and methods The medical records of 23 patients treated with definitive or postoperative RT between 1992 and 2010 at the University of Florida were retrospectively reviewed. Fifteen patients (65%) received primary surgery and postoperative RT. Radiation doses ranged from 59.0 to 74.8 Gy (median, 70.2 Gy). The median follow-up time for all patients was 3.0 years (range, 0.9–19.9), and for living patients was 7.7 years (range, 2.5–19.9). Results The actuarial 5-year survival outcomes were as follows: progression-free survival, 42%; cause-specific survival, 43%; and overall survival, 32%. Actuarial 5-year disease control rates were as follows: local control (infield or marginal), 74%; local-regional control (excluding leptomeningeal spread), 58%, regional control 78%, freedom from leptomeningeal recurrence, 72%, and distant metastasis-free survival, 73%. Five of the 8 (62.5%) patients treated with definitive RT died with disease, and 6 of the 15 patients (40%) treated with primary surgery and postoperative RT died with disease. Three patients (13%) experienced severe complications including unilateral eye removal, osteoradionecrosis of the maxilla requiring hyperbaric oxygen and surgery, and brain necrosis. One patient died due to an infected bone graft and brain abscess. Conclusions A multimodal approach is best when treating SNUC patients. The prognosis for patients treated with definitive RT ± chemotherapy is less promising than for those who receive surgery and postoperative RT ± chemotherapy. Severe complications occur in about 17% of patients due to the high dose of RT alone or combined with surgery required for acceptable disease control.

Objectives The aim of this study was to evaluate the long-term effectiveness and complications of radiotherapy (RT) in the treatment of patients with mucosal melanomas of the head and neck. Materials and methods The medical records of 21 patients treated with definitive or postoperative (RT) between 1974 and 2011 at the University of Florida Department of Radiation Oncology in Gainesville, FL, and the University of Florida Proton Therapy Institute in Jacksonville, FL, were retrospectively reviewed under an Institutional Review Board-approved protocol. Primary sites included nasal cavity, oropharynx, and paranasal sinuses. Sixteen patients (76%) received surgery and postoperative RT and 5 patients (24%) received RT alone. Seventeen patients received photon RT alone, whereas 4 patients received combined photon-based and proton-based RT. Median follow-up for all patients was 1.05 years (range, 0.36 to 12.97 y); median follow-up for survivors was 2.2 years (range 0.9 to 13.0 y). Results The 5-year outcomes were: local control, 79%; regional control, 85%; local-regional control, 65%; distant metastasis-free survival, 20%; cause-specific survival, 22%; and overall survival, 22%. Three patients (14%) experienced severe complications including bilateral blindness and skin necrosis. Conclusions Definitive or postoperative RT for mucosal melanoma of the head and neck yields fairly good local-regional control of disease. The prognosis for patients treated with definitive RT is less promising than for those who receive surgery and postoperative RT.

A single-institution review of long-term outcomes and factors affecting local control (LC) following radiotherapy for non-metastatic medulloblastoma.From 1963 to 2008, 50 children (median age, 7.3 years; range 1.2-18.5) with stage M0 medulloblastoma were treated with radiotherapy; half underwent a gross total resection (no visible residual tumor) or near-total resection (1.5 cm(3) of gross disease remaining after resection). Median craniospinal dose was 28.8 Gy (range 21.8-38.4 Gy). Median total dose to the posterior fossa was 54.3 Gy (range 42.4-64.8 Gy). Eighteen patients (36%) received chemotherapy as part of multimodality management, including 11 who received concurrent chemotherapy.Median follow-up was 15.7 years (range 0.3-44.4 years) for all patients and 26.6 years (range 7.3-44.4 years) for living patients. The 10-year overall survival, cancer-specific survival, and progression-free survival rates were 65%, 65%, and 69%. The 10-year LC rate was 84% and did not significantly change across eras. Four percent of patients experienced local progression five years after treatment. On univariate analysis, chemotherapy and overall duration of radiotherapy ≤ 45 days were associated with improved LC. Patients receiving chemotherapy had a 10-year 100% LC rate versus 76% in patients not receiving chemotherapy (p = 0.0454). When overall radiotherapy treatment lasted ≤ 45 days, patients experienced a superior 95% 10-year LC rate (vs. 73% in patients treated45 days; p = 0.0419). Three patients (6%) died from treatment complications, including radionecrosis/cerebellar degeneration, severe cerebral edema leading to herniation, and secondary malignancy.While we cannot draw definitive conclusions given the retrospective nature of our study, our long-term data suggest that reductions in craniospinal dose and boost target volume to reduce toxicity have not compromised disease control in the modern era. Our data also support analyses that implicate duration of radiotherapy, rather than interval between surgery and radiotherapy, as a factor in LC. Chemotherapy in multimodality management of medulloblastoma may have an underappreciated role in improving LC rates.

The purpose of this study is to review late toxicity following craniospinal radiation for early-stage medulloblastoma.Between 1963 and 2008, 53 children with stage M0 (n = 50) or M1 (n = 3) medulloblastoma were treated at our institution. The median age at diagnosis was 7.1 years (range 1.2-18.5). The median craniospinal irradiation (CSI) dose was 28.8 Gy (range 21.8-38.4). The median total dose, including boost, was 54 Gy (range 42.4-64.8 Gy). Since 1963, the CSI dose has been incrementally lowered and the high-risk boost volume reduced. Twenty-one patients (40%) received chemotherapy in their initial management, including 12 who received concurrent chemotherapy. Late sequelae were evaluated by analyzing medical records and conducting phone interviews with surviving patients and/or care-takers. Complications were graded using the NCI Common Terminology Criteria for Adverse Events, version 4.0.The median follow-up for all patients was 15.4 years (range 0.4-44.4) and for living patients it was 24 years (range 5.6-44.4). The overall survival, cause-specific survival, and progression-free survival rates at 10 years were 67%, 67%, and 71%, respectively. Sixteen patients (41% of patients who survived five years or more) developed grade 3 + toxicity; 15 of these 16 patients received a CSI dose23.4 Gy. The most common grade 3 + toxicities for long-term survivors are hearing impairment requiring intervention (20.5%) and cognitive impairment (18%) prohibiting independent living. Four patients developed secondary (non-skin) malignancies, including three meningiomas, one rhabdomyosarcoma, and one glioblastoma multiforme. Three patients (5.6%) died from treatment complications, including radionecrosis, severe cerebral edema, and fatal secondary malignancy.Ongoing institutional and cooperative group efforts to minimize radiation exposure are justified given the high rate of serious toxicity observed in our long-term survivors. Follow-up through long-term multidisciplinary clinics is important and warranted for all patients exposed to radiotherapy in childhood.

Purpose/Objective(s): To assess postoperative changes of cerebral glucose metabolism in craniopharyngioma patients receiving proton therapy. Materials/Methods: From 2011 to 2012, 17 patients enrolled in a prospective proton therapy trial for craniopharyngioma and received longitudinal PET and MR imaging for tumor and normal tissue response. Sixteen of them underwent craniotomies before baseline FDG PET studies followed by proton therapy of 54 CGEs. One did not require surgical intervention before radiation. Patient FDG PET images were nonlinearly warped to a 3D reference template in Talairach coordinates created from images of normal subjects. Left-right asymmetry of the count per voxel in each of 63 anatomical regions and region-based statistics of activity were computed. Regional asymmetry was considered significant when its Z score exceeded two standard deviations of normal population. To exclude any potential bias in PET acquisition, 12 control children with extracranial diseases but normal cerebral PET scans were also analyzed. Results: Median age of craniopharyngioma patients at diagnosis was 13 years (range, 4-18 years). Median time from craniotomies to baseline PET studies and from PET to proton therapy was 136 days (range, 7-226 days) and 32 days (range, 20-52 days). Significantly decreased glucose uptake was most prominent in right frontal lobe, striatum, and thalamus. It occurred in 7 of 10 patients who underwent transcranial craniotomies and in 2 of 3 patients receiving endoscopic craniostomy for cyst drainage, but in none of the 4 patients who received transphenoidal surgery or no surgery. Significant asymmetry in superior frontal gyrus is related to the surgical approach (89% occurrence in right frontal, bifrontal, and interhemispheric approaches vs 0% in other approaches). Significant asymmetry in caudate nucleus, putamen, and thalamus likely resulted from mass effect, venous occlusion, and surgical damage. A large, but not significant, uptake asymmetry (averaged 9%) in the inferior occipital gyrus was observed in both craniopharyngioma and control patients. This asymmetry is possibly due to the left occipital petalia commonly seen in right handers. None of the uptake asymmetry in superior frontal lobe, striatum, and thalamus was significant in control subjects. Conclusions: Postoperative metabolic abnormalities in the right superior frontal gyrus, striatum, and thalamus were noted in craniopharyngioma patients before proton therapy. The latter two are of particular interest since they subsequently receive the tumoricidal dose or are in high dose gradient regions and play an important role in regulation of motor control, sensory function, memory, sleep, and consciousness. The association with observed clinical deficits before and after proton therapy in this population will be reported. Author Disclosure: C. Hua: None. H.M. Conklin: None. M.A. Madey: None. D.J. Indelicato: None. B.L. Shulkin: None. T.E. Merchant: None.