Neurosurgery: Skull Base Craniofacial Trauma.

Much of craniofacial trauma involves the frontal sinuses. Because of its response to injury, the frontal sinus mucosa has an innate ability to develop mucoceles, and if infected, mucopyocoeles. This article presents a therapeutic algorithm for all forms of craniofacial trauma with concentration on the most severe injury-the through and through fracture and its surgical remediation.

Evaluating risk factors and predicting complications in head and neck reconstructive surgery.

PURPOSE OF REVIEW: Complications in head and neck reconstructive surgery can have devastating effects. There is a tremendous body of literature examining risk factors that may predict complications in this patient population, thereby minimizing or avoiding adverse outcomes. RECENT FINDINGS: Rotational thromboelastometry may provide a mechanism to predict coagulopathy in patients undergoing microvascular reconstruction. Surveillance of serum C-reactive protein levels may provide an additional tool for early intervention in wound complications Controversy persists in the literature regarding specific risk factors and associated perioperative complications. SUMMARY: Perioperative medical and surgical complications are commonplace in the management of complex oncologic disease and attendant defect reconstructions. Potential risk factors have been examined exhaustively in the literature without a consensus being established.

Combined Balloon Test Occlusion and SPECT Analysis for Carotid Sacrifice: Angiographic Predictors for Success or Failure?

Objectives To evaluate angiographic patterns that may predict the success or failure of carotid artery balloon test occlusion (BTO) and single-photon emission computed tomography (SPECT) analysis for carotid sacrifice. Study Design This is a retrospective nonrandomized study. Study Setting Conducted at the University of California Davis Medical Center, Sacramento, California. Patients A total of 31 patients, ranging from 24 to 83 years of age, with a mean age of 61 years (22 men, 9 women) with head and neck cancer (26 patients), malignant glomus tumor (1 patient) or giant carotid aneurysms (4 patients) as possible candidates for surgical carotid artery sacrifice were evaluated from September 2005 to September 2012. Methods All patients underwent unilateral internal carotid artery balloon test occlusion with SPECT analysis (20 mCi technetium 99m-hexamethyl propyleneamine oxime [HMPAO]) imaging before and during carotid occlusion. Carotid angiography with carotid cross-compression (manual compression of the cervical artery contralateral to the side of contrast injection) was used to analyze filling through the anterior communicating artery to the contralateral hemisphere. Intervention The balloon occlusion was terminated in two patients because of deterioration of the neurologic exam. Main Outcome Measures All patients who passed the neurologic examination during BTO and also passed the SPECT occlusive study underwent successful carotid sacrifice without neurologic sequelae. Patients failing the occlusive neurologic examination and/or the SPECT study elected chemoradiation, with the exception of one patient who underwent a successful carotid bypass graft and carotid resection. Results The success of carotid sacrifice in patients passing both the occlusive test and the SPECT analysis for carotid sacrifice was 100%. Three patients failed both the BTO and the SPECT, with two demonstrating no anterior circulation cross-fill, but one showed some cross-fill. Six additional patients passed the BTO but failed the SPECT, with poor cross-fill in five patients. In addition, three patients who had excellent cross-fill through the anterior communicating artery to the contralateral hemisphere failed the SPECT examination in two cases and failed both tests in another case.

Level IB nodal involvement in oropharyngeal carcinoma: implications for submandibular gland-sparing intensity-modulated radiotherapy.

OBJECTIVES/HYPOTHESIS: Submandibular gland-sparing intensity-modulated radiotherapy (SMG-sparing IMRT) has been proposed to reduce xerostomia following head and neck irradiation. However, the safety of this practice has been questioned. Data from a large surgical series of oropharyngeal carcinoma patients were extracted to identify clinicopathological correlates for submandibular involvement and to create a risk stratification scheme to guide decision making to refine selection guidelines for SMG-sparing IMRT. STUDY DESIGN: Clinicopathologic analysis. METHODS: The medical records of 153 consecutive patients with squamous cell carcinoma of the oropharynx treated by primary surgery and neck dissection were reviewed. Univariate and multivariate analysis was performed with logistic regression to identify factors predictive of submandibular involvement. Recursive partitioning was used to develop risk stratification schemas based on preoperative data alone and in combination with pathologic data to guide treatment decisions in the definitive and postoperative settings, respectively. RESULTS: Submandibular (level IB) nodal dissection was performed in 119 heminecks (85 ipsilateral and 17 contralateral). The incidence of submandibular involvement was 18%. Young age, T3-4 disease, N2b-3 disease, and perineural invasion were identified as risk factors for submandibular nodal involvement on multivariate analysis (P < .01). Three distinct risk groups for submandibular involvement were identified: age >60 years and N0-2a disease (low risk, 2%), age ≤60 years and T1-2N2b-3 (intermediate risk, 16%), age ≤60 years and T3-4N2b-3 disease (high risk, 57%). CONCLUSIONS: These data provide assurances that SMG-sparing IMRT can reasonably be offered to appropriately selected patients. Risk stratification schemas were successfully developed for SMG-sparing IMRT in both the definitive and adjuvant settings.

Comparison of functional outcomes and quality of life between transoral surgery and definitive chemoradiotherapy for oropharyngeal cancer.

BACKGROUND: The purpose of this study was to compare patient-reported outcomes between patients treated by initial transoral resection versus definitive chemoradiotherapy for oropharyngeal cancer. METHODS: Thirty-one patients with oropharyngeal cancer treated by initial transoral CO2 laser microsurgery (n = 16) or robotic surgery (n = 15) followed by postoperative radiotherapy were identified. Each patient was matched to 1 control patient treated by definitive chemoradiotherapy. The University of Washington Quality of Life (UW-QOL) scores at 1 year were compared. RESULTS: No significant differences were observed in any of the UW-QOL functional domains at 1 year with the exception of swallowing (91.5 vs 72.1; p = .01). Twenty-three of 31 patients (74%) treated by transoral surgery reported swallowing "as well as ever," versus 10 of 31 patients (32%) treated by chemoradiotherapy. CONCLUSION: Similar quality of life was observed among patients treated by transoral surgery or chemoradiotherapy. Although the rates of subjective swallowing dysfunction were higher among the latter, confounding biases must be considered.

Widefield optical imaging of changes in uptake of glucose and tissue extracellular pH in head and neck cancer.

The overall objective of this study was to develop an optical imaging approach to simultaneously measure altered cell metabolism and changes in tissue extracellular pH with the progression of cancer using clinically isolated biopsies. In this study, 19 pairs of clinically normal and abnormal biopsies were obtained from consenting patients with head and neck cancer at University of California, Davis Medical Center. Fluorescence intensity of tissue biopsies before and after topical delivery of 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose) and Alexa 647-pHLIP [pH (low) insertion peptide] was measured noninvasively by widefield imaging, and correlated with pathologic diagnosis. The results of widefield imaging of clinical biopsies demonstrated that 2-NBDG and pHLIP peptide can accurately distinguish the pathologically normal and abnormal biopsies. The results also demonstrated the potential of this approach to detect subepithelial lesions. Topical application of the contrast agents generated a significant increase in fluorescence contrast (3- to 4-fold) in the cancer biopsies as compared with the normal biopsies, irrespective of the patient and location of the biopsy within a head and neck cavity. This unpaired comparison across all the patients with cancer in this study highlights the specificity of the imaging approach. Furthermore, the results of this study indicated that changes in intracellular glucose metabolism and cancer acidosis are initiated in the early stages of cancer, and these changes are correlated with the progression of the disease. In conclusion, this novel optical molecular imaging approach to measure multiple biomarkers in cancer has a significant potential to be a useful tool for improving early detection and prognostic evaluation of oral neoplasia.

Patterns of nodal involvement for clinically N0 salivary gland carcinoma: refining the role of elective neck irradiation.

BACKGROUND: The purpose of this study was to analyze the pattern of occult cervical lymph node metastasis among patients with clinically N0 salivary gland carcinoma. METHODS: One hundred nineteen patients underwent primary surgery and ipsilateral neck dissection for clinically N0 carcinomas of the major and minor salivary glands. Eighty patients (67%) had parotid tumors. Distribution of T classification was: T1 (18%), T2 (28%), T3 (23%), and T4 (32%). RESULTS: Twenty-five patients (21%) had pathological cervical disease. The incidence was highest among patients with adenocarcinoma (35%) and high-grade mucoepidermoid carcinoma (35%). The most common site of cervical lymph node metastasis was level II (71%), followed by level III (15%), and level IB (8%). On multivariate analysis, histological subtype was independently predictive of occult pathological lymph node metastasis (p < .001). CONCLUSION: The likelihood of occult cervical lymph node metastasis for patients with salivary gland carcinoma is driven predominantly by histological subtype. Implications for elective neck irradiation are discussed.

Tobacco use among long-term survivors of head and neck cancer treated with radiation therapy.

PURPOSE: The objective of this study is to determine the prevalence of tobacco consumption (i.e., cigarette use) among survivors of head and neck cancer after treatment with radiation therapy (RT). METHODS AND MATERIALS: A longitudinal study was conducted with 230 patients previously treated with RT for squamous cell carcinoma of the head and neck. All patients were clinically without evidence of disease and had a minimum of 1 year follow-up. Patients were summarily asked about the use of tobacco products at each follow-up visit. To explore for associations between potential predictors of post-RT smoking, the Chi-square test and Spearman's correlation coefficient were employed. RESULTS: The percentage of patients who were actively smoking was 21%, 21%, and 20%, at 1, 2, and 3 years post-RT, respectively. When the analysis was limited to patients with a former smoking history (i.e., excluding all never-smokers), these percentages increased to 32%, 27%, and 25%, respectively. The intensity of smoking at follow-up ranged from one cigarette daily to 2.5 packs daily. Forty-two of 76 (55%) patients who were smoking at diagnosis were found to be smoking at 1-year follow-up compared to 7 of 154 patients who were not (p < 0.001). The only factor that significantly predicted for persistent smoking at follow-up was the presence of a preexisting psychiatric condition (most commonly, a mood disorder) at initial cancer diagnosis. CONCLUSIONS: A significant proportion of former smokers are actively smoking during follow-up despite having completed intensive RT and having their cancers evidently under control. Innovative interventional approaches to target those at highest risk for continued smoking are warranted.

Improved clinical outcomes with multi-modality therapy for sinonasal undifferentiated carcinoma of the head and neck.

OBJECTIVE: To examine outcomes among patients treated for sinonasal undifferentiated carcinoma (SNUC) of the head and neck. STUDY DESIGN: Retrospective review. METHODS: The records of 16 consecutive patients with newly diagnosed, non-metastatic SNUC were analyzed. Initial treatment consisted of: surgery alone (6 patients), surgery with post-operative chemoradiotherapy (4 patients), and primary radiation therapy with concurrent chemotherapy (6 patients). RESULTS: The median survival for patients treated by surgery followed by postoperative chemoradiotherapy was 30 months compared to 7 months and 9 months for patients treated by surgery alone and upfront chemoradiotherapy, respectively (p=0.20). The 2-year locoregional control was 18% for patients treated with upfront chemoradiotherapy, 37% for patients treated with surgery alone, and 78% for patients treated with surgery plus chemoradiotherapy (p=0.49). CONCLUSION: While the potential role of selection bias must be considered, multi-modality therapy using surgery and post-operative chemoradiotherapy yielded the most favorable outcomes for SNUC and should be recommended whenever feasible.

Depression among long-term survivors of head and neck cancer treated with radiation therapy.

IMPORTANCE: The diagnosis and subsequent treatment of head and neck cancer can have a potentially devastating impact on psychosocial functioning. Although the long-term physical adverse effects of radiation therapy (RT) for head and neck cancer have been well described, relatively few studies have evaluated psychosocial functioning after treatment. OBJECTIVE: To determine the prevalence of self-reported depression among survivors of head and neck cancer returning for follow-up after being treated with RT. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis among 211 comprehensive cancer center patients with squamous cell carcinoma of the head and neck, who had been previously treated with RT and were disease-free with at least 1 year of follow-up. Patients with a history of mood disorder, use of mental health services in the past, or previous or current use of antidepressants or anxiolytics, excluding sleep medications, were specifically excluded. INTERVENTIONS: The University of Washington Quality of Life instrument (UW-QOL), a brief, previously validated, self-administered questionnaire, was used to analyze rates of depression. MAIN OUTCOMES AND MEASURES: The UW-QOL assigned scores of 0, 25, 50, 75, and 100 subjective responses of mood being "extremely depressed," "somewhat depressed," "neither in a good mood or depressed," "generally good," and "excellent," respectively. RESULTS: The mean mood score did not differ at 1, 3, and 5 years after treatment, with scores of 52.0, 55.7, and 62.1, respectively. The proportion of patients who reported their mood as "somewhat depressed" or "extremely depressed" was 17%, 15%, and 13% at 1, 3, and 5 years, respectively. Variables that were significantly associated with post-RT depression included the presence of tracheostomy tube or laryngeal stoma (P = .01), gastrostomy tube dependence (P = .01), and continued smoking at the time of follow-up (P < .001). Among the patients reporting their mood as either "somewhat depressed" or "extremely depressed" at 1, 3, and 5 years, the proportion using antidepressants at the time was 6%, 11%, and 0%, respectively. The corresponding proportion of patients actively undergoing or seeking psychotherapy and/or counseling was 3%, 6%, and 0%, respectively. CONCLUSIONS AND RELEVANCE: Despite a relatively high rate of depression among patients with head and neck cancer in the post-RT setting, mental health services are severely underutilized.

Feasibility and toxicity of concurrent chemoradiation for elderly patients with head and neck cancer.

OBJECTIVES: Although concurrent chemoradiation is increasingly used for patients with locally advanced head and neck cancer, many elderly patients receive radiation alone due to toxicity concerns. We evaluate acute and late toxicity among patients age ≥ 65 who received concurrent chemoradiation for head and neck cancer. DESIGN: Retrospective review. SETTING: Tertiary care center. PARTICIPANTS: Between 6/2003 and 8/2011, 40 consecutive patients age ≥ 65 underwent combined chemoradiation for head and neck cancer. Ten patients were treated in the postoperative setting and 30 underwent definitive chemoradiation. Twenty-eight patients received concurrent platinum-based chemotherapy and 12 received concurrent weekly paclitaxel. Treatment plans were designed to provide a dose of 66-72 Gy at 2-2.12 Gy/fraction to >95% of the gross tumor volume in the definitive setting or for positive margins and 60-66 Gy at 2 Gy/fraction post-operatively. Median follow-up was 23.2 months (range: 0-94.4 months). MAIN OUTCOMES MEASURES: Acute skin and mucosal toxicity, unplanned treatment interruptions, and chronic treatment related toxicity including gastrostomy tube dependence as graded by the CTCAE v3.0. RESULTS: Eight patients (20%) required a radiation treatment break of ≥ 3 days. Thirteen (33%) required unplanned hospitalization during or immediately following treatment. No grade 4+ skin or mucosal toxicity was noted. Five patients remained PEG tube dependent at >1 year. One patient developed non-healing mandibular osteoradionecrosis >3 years following chemoradiation. The 2-year Kaplan-Meier estimate of overall survival was 55%. CONCLUSION: Higher-than-expected rates of in-patient hospitalization with significant acute toxicity were noted in this cohort with a correspondingly high rate of radiation treatment breaks. Late toxicity rates were similar to those observed in historical controls with younger patients. Careful patient selection criteria should be employed for elderly patients considering concurrent chemoradiation for head and neck cancer.

Mucoepidermoid carcinoma of the parotid gland treated by surgery and postoperative radiation therapy: clinicopathologic correlates of outcome.

OBJECTIVES/HYPOTHESIS: To determine clinical and pathological correlates of outcome among patients treated by surgery and postoperative radiation therapy for mucoepidermoid carcinoma of the parotid gland. STUDY DESIGN: Retrospective review. METHODS: The medical records of 61 patients treated by surgery and postoperative radiation therapy for localized mucoepidermoid carcinoma of the parotid gland were retrospectively reviewed in an attempt to identify clinicopathologic correlates of overall survival. Secondary endpoints included local-regional control, distant metastasis-free survival, and complications. RESULTS: The 3- and 5-year estimates of overall survival were 85% and 79%, respectively. Multivariate analysis identified high tumor grade (hazard ratio [HR] = 7.92) and T4 disease (HR = 3.35) as independent predictors of decreased survival, with the former also predicting for distant metastasis and the latter predicting for local-regional recurrence. The 5-year estimate of overall survival was 83% for patients with non-high-grade tumors, compared to 52% for those with high-grade histology (P = 0.001). Late complications included trismus (2 patients), osteoradionecrosis (1 patient), and hearing loss (1 patient). CONCLUSION: Patients with high-grade tumors and T4 disease are at increased risk for treatment failure after surgery and postoperative radiation therapy for mucoepidermoid carcinoma of the parotid gland. Investigative strategies to improve outcome should be considered for these particular patients in the future.

High-resolution optical molecular imaging of changes in choline metabolism in oral neoplasia.

This study was aimed at developing an optical molecular imaging approach to measure differences in uptake and intracellular retention of choline in clinically isolated tissue biopsies from head and neck cancer patients. An optically detectable analogue of choline (propargyl choline) was synthesized and evaluated in 2D and 3D models and clinically isolated paired biopsies (n = 22 biopsies). Fluorescence contrast between clinically abnormal and normal tissues based on uptake and intracellular retention of propargyl choline was measured and correlated with pathologic diagnosis. Results in 2D and 3D models demonstrated a rapid uptake of propargyl choline in cancer cells, uniform permeation in tissue models, and specific detection of intracellular entrapped propargyl choline using the click chemistry reaction with an azide-modified Alexa 488 dye. Fluorescence imaging measurements following topical delivery of propargyl choline in clinically isolated biopsies showed that the mean fluorescence intensity (MFI) of neoplastic tissues was four-fold to five-fold higher than the MFI of clinically and pathologically normal samples. This difference in fluorescence contrast was measured on the basis of comparison of paired biopsy sets isolated from individual patients as well as comparison of clinically abnormal and normal biopsies independent of anatomic locations in the head and neck cavity and across diverse patients. In conclusion, a novel imaging approach based on monoalkyne-modified choline was developed and validated using cell and tissue models. Results in clinically isolated tissue biopsies demonstrate a significant fluorescent contrast between neoplastic and normal tissues and illustrate high specificity of the optical imaging approach.

Optical molecular imaging detects changes in extracellular pH with the development of head and neck cancer.

Noninvasive localized measurement of extracellular pH in cancer tissues can have a significant impact on the management of cancer. Despite its significance, there are limited approaches for rapid and noninvasive measurement of local pH in a clinical environment. In this study, we demonstrate the potential of noninvasive topical delivery of Alexa-647 labeled pHLIP (pH responsive peptide conjugated with Alexa Fluor(®) 647) to image changes in extracellular pH associated with head and neck squamous cell carcinoma using widefield and high resolution imaging. We report a series of preclinical analyses to evaluate the optical contrast achieved after topical delivery of Alexa-647 labeled pHLIP in intact fresh human tissue specimens using widefield and high-resolution fluorescence imaging. Using topical delivery, Alexa-647 labeled pHLIP can be rapidly delivered throughout the epithelium of intact tissues with a depth exceeding 700 µm. Following labeling with Alexa-647 labeled pHLIP, the mean fluorescent contrast increased four to eight fold higher in clinically abnormal tissues as compared to paired clinically normal biopsies. Furthermore, the imaging approach showed significant differences in fluorescence contrast between the cancer and the normal biopsies across diverse patients and different anatomical sites (unpaired comparison). The fluorescence contrast differences between clinically abnormal and normal tissues were in agreement with the pathologic evaluation. Topical application of fluorescently labeled pHLIP can detect and differentiate normal from cancerous tissues using both widefield and high resolution imaging. This technology will provide an effective tool to assess tumor margins during surgery and improve detection and prognosis of head and neck cancer.

Utility of daily image guidance with intensity-modulated radiotherapy for tumors of the base of skull.

BACKGROUND: This study was carried out to report our experience using intensity-modulated radiotherapy (IMRT) with daily image-guided radiotherapy (IGRT) for tumors involving the base of skull. METHODS: In all, 100 patients were prospectively treated with IMRT to a median dose of 64 Gy (range, 45-70 Gy). Daily helical megavoltage computed tomography (MVCT) scans were obtained as part of an IGRT registration protocol for patient alignment. RESULTS: The 2-year local-regional control was 91%. A total of 3295 daily MVCT scans were obtained. The mean shift to account for interfraction motion was 1.18 ± 1.75 mm, 1.81 ± 1.34 mm, and 1.33 ± 1.19 mm for the medial-lateral (ML), superior-inferior (SI), and anterior-posterior (AP) directions, respectively. Pretreatment shifts of >3 mm occurred in 10%, 26%, and 18%, in the ML, SI, and AP directions, respectively. CONCLUSIONS: The feasibility and efficacy of daily IGRT as a complement to IMRT for skull base were demonstrated.

Prospective trial of high-dose reirradiation using daily image guidance with intensity-modulated radiotherapy for recurrent and second primary head-and-neck cancer.

PURPOSE: To report a single-institutional experience using intensity-modulated radiotherapy with daily image-guided radiotherapy for the reirradiation of recurrent and second cancers of the head and neck. METHODS AND MATERIALS: Twenty-one consecutive patients were prospectively treated with intensity-modulated radiotherapy from February 2006 to March 2009 to a median dose of 66 Gy (range, 60-70 Gy). None of these patients received concurrent chemotherapy. Daily helical megavoltage CT scans were obtained before each fraction as part of an image-guided radiotherapy registration protocol for patient alignment. RESULTS: The 1- and 2-year estimates of in-field control were 72% and 65%, respectively. A total of 651 daily megavoltage CT scans were obtained. The mean systematic shift to account for interfraction motion was 1.38 ± 1.25 mm, 1.79 ± 1.45 mm, and 1.98 ± 1.75 mm for the medial-lateral, superior-inferior, and anterior-posterior directions, respectively. Pretreatment shifts of >3 mm occurred in 19% of setups in the medial-lateral, 27% in the superior-inferior, and 33% in the anterior-posterior directions, respectively. There were no treatment-related fatalities or hospitalizations. Complications included skin desquamation, odynophagia, otitis externa, keratitis, naso-lacrimal duct stenosis, and brachial plexopathy. CONCLUSIONS: Intensity-modulated radiotherapy with daily image guidance results in effective disease control with relatively low morbidity and should be considered for selected patients with recurrent and second primary cancers of the head and neck.

Evaluation of the planning target volume in the treatment of head and neck cancer with intensity-modulated radiotherapy: what is the appropriate expansion margin in the setting of daily image guidance?

PURPOSE: To compare patterns of disease failure among patients treated with intensity-modulated radiotherapy (IMRT) in conjunction with daily image-guided radiotherapy (IGRT) for head and neck cancer, according to the margins used to expand the clinical target volume (CTV) to create a planning target volume (PTV). METHODS AND MATERIALS: Two-hundred and twenty-five patients were treated with IMRT for squamous cell carcinoma of the head and neck. Daily IGRT scans were acquired using either kilovoltage or megavoltage volumetric imaging prior to each delivered fraction. The first 95 patients were treated with IMRT with 5-mm CTV-to-PTV margins. The subsequent 130 patients were treated using 3-mm PTV expansion margins. RESULTS: Two-year estimates of overall survival, local-regional control, and distant metastasis-free survival were 76%, 78%, and 81%, respectively. There were no differences with respect to any of these endpoints among patients treated with 5-mm and 3-mm PTV expansion margins (p > 0.05, all). The 2-year local-regional control rate for patients treated with IMRT with 5-mm and 3-mm PTV margins was 78% and 78%, respectively (p = 0.96). Spatial evaluation revealed no differences in the incidences of marginal failures among those treated with 5-mm and 3-mm PTV margins. CONCLUSIONS: The use of 3-mm PTV expansion margins appears adequate and did not increase local-regional failures among patients treated with IMRT for head and neck cancer. These data demonstrate the safety of PTV reduction of less than 5 mm and support current protocols recommending this approach in the setting of daily IGRT.