Radiotherapy-induced common carotid pseudoaneurysm presenting with initially occult upper airway hemorrhage and successfully treated by endovascular stent graft.

Radiation induced carotid vasculopathy may present as steno-occlusive disease or less commonly as a pseudoaneurysm. The latter most often presents with a pulsatile mass but is a potential cause of life threatening hemorrhage. We present a case of a small common carotid artery (CCA) pseudoaneurysm that was initially dismissed as the cause of the patients presenting epistaxis given its small size and location. After standard bilateral internal maxillary artery embolizations failed to prevent significant subsequent pharyngeal and tracheal blood loss and serial imaging demonstrated a progressive enlargement of the pseudoaneurysm, a stent graft was successfully placed across the lesion. At five months post stenting, follow-up imaging of the neck showed a stable obliteration of the pseudoaneurysm, good arterial patency, and the patient remained free of recurrent hemorrhage. This case demonstrates that even a small carotid pseudoaneurysm, can present with pharyngeal hemorrhage and should be treated aggressively--with endovascular stent grafting being a preferred treatment modality for arterial lesions in the irradiated neck.

Weekly carboplatin and paclitaxel followed by concomitant paclitaxel, fluorouracil, and hydroxyurea chemoradiotherapy: curative and organ-preserving therapy for advanced head and neck cancer.

PURPOSE: The paclitaxel, fluorouracil, and hydroxyurea regimen of paclitaxel, infusional fluorouracil, hydroxyurea, and twice-daily radiation therapy (TFHX) administered every other week has resulted in 3-year survival rates of 60% of stage IV patients. Locoregional and distant failure rates were 13% and 23%, respectively. To reduce distant failure rates, we added a brief course of induction chemotherapy to TFHX. PATIENTS AND METHODS: Sixty-nine patients received six weekly doses of carboplatin (AUC2) and paclitaxel (135 mg/m2) followed by five cycles of TFHX. RESULTS: Ninety-six percent had stage IV disease. Response to induction chemotherapy was partial response 52% and complete response (CR) 35%. Symptomatically, there was a significant reduction in mouth and throat pain. The most common grade 3 or 4 toxicity was neutropenia (36%). Best response following completion of TFHX was CR in 83%. Toxicities of TFHX consisted of grade 3 or 4 mucositis (74% and 2%) and dermatitis (47% and 14%). At a median follow-up of 28 months, locoregional or systemic disease progression were each noted in five patients. The overall 3-year progression-free survival was 80% (95% confidence interval [CI], 71% to 90%), and the 2- and 3-year overall survival rates were 77% (95% CI, 66% to 87%) and 70% (95% CI, 59% to 82%), respectively. At 12 months, five patients were completely feeding-tube dependent. CONCLUSION: Administration of carboplatin and paclitaxel before TFHX chemoradiotherapy results in high response activity and may decrease distant failure rates. Overall survival, progression, and organ preservation/functional outcome data support definitive evaluation of this approach.

Induction chemotherapy followed by concomitant TFHX chemoradiotherapy with reduced dose radiation in advanced head and neck cancer.

PURPOSE: Induction chemotherapy with carboplatin and paclitaxel followed by concomitant TFHX (paclitaxel, infusional 5-fluorouracil, hydroxyurea, and twice-daily radiation therapy administered every other week) has resulted in 70% 3-year survival in stage IV patients. Locoregional and distant control rates were 94 and 93%, respectively. In an attempt to decrease toxicity without compromising local control, a second cohort of patients was treated with a lower dose of radiation to sites of potential microscopic disease. EXPERIMENTAL DESIGN: Sixty-four patients were entered on study. Patients received six weekly doses of carboplatin (area under the curve 2) and paclitaxel (135 mg/m2) followed by five cycles of TFHX. The radiation dose to gross disease was 75 Gy as in the previous trial. The radiation dose to high-risk microscopic disease was reduced from 60 to 54 Gy, and the dose to low-risk microscopic disease was reduced from 45 to 39 Gy. RESULTS: Ninety-seven percent of patients had stage IV disease. The response rate to induction chemotherapy was 82% with a complete response rate of 42%. At the completion of therapy the clinical complete response rate rose to 100% with a median follow-up of 29 months. The actuarial 2 and 3-year survival was 77 and 70%, respectively. Five patients developed progressive disease for an overall 3-year progression-free survival of 90%. Two patients failed in locoregional sites alone, resulting in a 3-year locoregional control of 97%. The 3-year systemic control was 95%. Four patients were completely feeding tube dependent at the time of analysis. Only 1 of these patients had normal swallowing function before treatment. CONCLUSIONS: In this second trial, induction chemotherapy with carboplatin and paclitaxel followed by TFHX chemoradiotherapy results in high survival and progression-free survival. The reduction in radiation dose did not compromise survival or disease control compared with our prior study using higher radiation doses. Data continues to support definitive evaluation of this approach.

Phase I study of concomitant chemoradiotherapy with paclitaxel, fluorouracil, gemcitabine, and twice-daily radiation in patients with poor-prognosis cancer of the head and neck.

PURPOSE: We previously demonstrated high locoregional control, in patients with poor-prognosis head and neck cancer (HNC), using paclitaxel, 5-fluorouracil, hydroxyurea, and concomitant hyperfractionated radiotherapy. In the present phase I trial, gemcitabine, a novel antimetabolite with strong radiation-enhancing activity, replaces hydroxyurea. We sought to determine the recommended phase II dose and clinical efficacy in poor-prognosis HNC patients. EXPERIMENTAL DESIGN: Seventy-two patients enrolled. Eligibility criteria included recurrent or second primary HNC, metastases or expected 2-year survival <20%. Chemoradiotherapy consisted of 5-fluorouracil, 600 mg/m(2)/d, for 5 days; paclitaxel, 100 mg/m(2) on Day 1; and concurrent 1.5 Gy twice-daily radiation for 5 days. Gemcitabine was dose escalated, 50-300 mg/m(2) on day 1. Cycles repeated every 14 days until the completion of chemoradiation. Dose-limiting toxicities (DLTs) included: neutropenic fever; grade > or =4 neutropenia or thrombocytopenia for >4 days; grade > or =4 mucositis or dermatitis for >7 days; or grade 3 toxicity necessitating chemotherapy dose reductions. Non-DLT dose reductions in 5-fluorouracil and/or paclitaxel were allowed. RESULTS: Seventy-nine percent of assessable patients experienced a clinical response. Five-year actuarial survival is 33.0%, and locoregional control is 61.4%. The recommended phase II dose of gemcitabine in this regimen is 100 mg/m(2) during cycles 1-5 (1 of 7 patients with DLT) or 200 mg/m(2) delivered only during cycles 3-5 (3 of 19 with DLT). Grades 3 and 4 mucositis (56 and 21%, respectively) and dermatitis (25 and 21%, respectively) were common. CONCLUSIONS: Gemcitabine, 5-fluorouracil, paclitaxel, and twice-daily radiation, delivered on alternating weeks, is active in patients with poor-prognosis HNC, although severe mucositis limits the clinical applicability of this regimen. Refinements in radiotherapy, including intensity-modulated radiation therapy, may improve the tolerance for this regimen.

Multicenter randomized Phase II study of paclitaxel (1-hour infusion), fluorouracil, hydroxyurea, and concomitant twice daily radiation with or without erythropoietin for advanced head and neck cancer.

PURPOSE: To expand on our experience with the combination of paclitaxel, fluorouracil, hydroxyurea, and twice daily irradiation (T-FHX) and to assess the impact of weekly administration of erythropoietin (r-HuEpo) on transfusion requirements, we conducted a Phase II multi-institutional trial with a simplified 1-h paclitaxel infusion schedule and randomized patients to receive weekly doses of r-HuEpo. PATIENTS AND METHODS: A total of 90 patients with locally advanced head and neck cancers (stage IV, 96%; N(2)/N(3), 66%) were treated on a regimen of 1-h infusion of paclitaxel (100 mg/m(2)/day, day 1), 120-h infusion of 5-fluorouracil (600 mg/m(2)/day, days 0-5); hydroxyurea 500 mg p.o. every 12 h for 11 doses; and radiation 150cGy bid, days 1-5 of each 14-day cycle repeated for five cycles over 10 weeks (7200-7500 cGy). Before initiating therapy, patients were randomized to receive r-HuEpo 40,000 IU s.c. once weekly. RESULTS: At median follow-up of 40 months, 3-year progression-free survival is 62%, locoregional control is 84%, and systemic control is 79%. Overall survival is 59%. Anemia, leucopenia, dermatitis, and mucositis were the most frequent grade 3 or 4 toxicities. Patients randomized to erythropoietin experienced less grade 2/3 anemia (52 versus 77%; P = 0.02), but transfusion requirements were not significantly different. CONCLUSIONS: T-FHX is an active and tolerable regimen inducing local tumor control and promising survival with organ preservation in high-risk patients. One h infusion of paclitaxel simplified the regimen without compromising efficacy. Addition of erythropoietin does not reduce the need for transfusion with this nonplatinum-containing regimen. T-FHX should be advanced to a randomized trial and compared with a cisplatin-based concomitant regimen.

Preoperative radiation therapy and its effects on outcomes in microsurgical head and neck reconstruction.

OBJECTIVE: Preoperative radiation therapy is considered a significant factor in head and neck reconstruction. STUDY AND DESIGN AND SETTING: In our consecutive series of 114 patients, 44 patients had prior head and neck irradiation. The 2 groups were compared on the basis of age, ischemic time, and flap size and were found not to be statistically different. The average ischemic time for the irradiated group was 94.1 minutes, and the average was 102.8 minutes for the nonirradiated group. The average flap size for the irradiated group was 69.5 cm 2 and was 72.0 cm 2 for the nonirradiated group. RESULTS: Using a single-factor analysis of variance, the 2 groups did not differ statistically. The overall major flap complication rate for both irradiated and nonirradiated groups was approximately 10%. CONCLUSION: Microvascular reconstruction was accomplished in both irradiated and nonirradiated head and neck patients, with a 99% total flap survival rate and a 10% major flap complication rate.

Prevalence of penicillin allergy in adults with peritonsillar abscess.

We noticed a seemingly high prevalence of penicillin allergy in patients who had been diagnosed with peritonsillar abscess (PTA) at our institution. To formally investigate this observation, we reviewed the emergency room (ER) records of 118 patients who had presented between Jan. 1, 1995, and Dec. 31, 1999, with suspected PTA. A diagnosis of PTA was confirmed by the presence of pus on incision and drainage in 78 of these patients (66.1%). The remaining 40 patients (33.9%) were diagnosed with peritonsillar cellulitis (PTC). Of the 78 patients with confirmed PTA, 13 (16.7%) self-reported an allergy to an antibiotic, including 11 (14.1%) who claimed to be allergic to penicillin. In the 40 patients with PTC, the corresponding figures were only 3 (7.5%) and 1 (2.5%). The difference between the PTA and PTC groups with respect to the prevalence of self-reported penicillin allergy was statistically significant (p < 0.05). We also compared the prevalence of antibiotic allergies in our patients with that of 1,893 consecutively presenting patients whose records had been entered into a pharmacy database at our institution. We found that the overall prevalence of patient-reported penicillin allergy in our PTA group was similar to that of the database population, although penicillin allergy did account for a greater percentage of all antibiotic allergies (84.6%) in our PTA group than in the larger population (62.8%). In our series, patients with PTA were more likely to have reported an allergy to penicillin than were patients without an abscess. Additionally, the prevalence of patient-reported antibiotic allergy is high at our institution. Although self-reported penicillin allergy may not represent a true hypersensitivity reaction, it can influence antibiotic selection and/or compliance. Prospective studies are needed to determine what influence allergic status and antibiotic choice has on abscess development.

Whole-Field Sequential Intensity-Modulated Radiotherapy for Local-Regional Advanced Head-and-Neck Squamous Cell Carcinoma.

PURPOSE: There is little published data on the technique and results of whole-field (WF) sequential intensity-modulated radiotherapy (S-IMRT) for patients with head-and-neck squamous cell carcinoma (HNSCC). We report the treatment outcomes, adverse events (AEs), and dosimetric parameters in local-regional advanced (LRA) HNSCC patients treated with the WF S-IMRT technique. METHODS: The IRB approved this retrospective study. Patients received WF S-IMRT with or without concomitant chemotherapy. Three separate IMRT plans corresponding to 3 planning target volumes were generated. This study reports patient and tumor characteristics, treatment-induced acute AEs based on CTCAE version 3.0, chronic AEs according to RTOG scale and treatment outcomes, local-regional control (LRC), distant metastases (DM), relapse-free survival (RFS), and overall survival (OS). RESULTS: Between January 2003 and December 2010, 103 patients with LRA HNSCC were treated either definitively or postoperatively with WF S-IMRT, with (99 patients) or without (4 patients) concurrent chemotherapy. The median age was 55 years (range, 30 to 89 y). The median cumulative target dose was 70 Gy (range, 60 to 75 Gy). At a median follow-up of 40 months (range, 4 to 95 mo), the 2- and 5-year rates of OS were 94% and 77%, RFS were 90% and 84%, LRC were 97% and 93%, and DM were 9% and 11%, respectively. Grade 3 acute AEs included mucositis (68%), dysphagia (35%), weight loss (19.6%), and xerostomia (7.8%). Chronic worst grade 3 AEs included xerostomia (21.9%), weight loss (12.8%), and dysphagia (12.5%). Chronic grade 3 AEs at last follow-up included weight loss (6.25%), dysphagia (6.2%), and xerostomia (6.2%). No patient had an acute or chronic grade 4 AE, brachial plexopathy, or spinal cord injury. CONCLUSIONS: WF S-IMRT results in excellent tumor control and an acceptable toxicity profile in LRA HNSCC patients treated with this technique.

Does laryngectomy improve swallowing after chemoradiotherapy? A case study.

Organ preservation protocols of high-dose chemoradiotherapy have become fairly common to treat head and neck cancers. However, significant swallowing problems can occur. This study examines swallowing, oral tongue pressures, and tongue base-to-pharyngeal wall pressures in a patient who underwent total laryngectomy for improvement of swallowing after chemoradiotherapy for treatment of a hypopharyngeal tumor. The patient underwent concurrent videofluorographic and manometric examination of swallowing and examination of oral tongue pressures after the laryngectomy. One healthy subject was used as a control. After the laryngectomy, the patient no longer aspirated; however, he could swallow only liquids and pureed foods. He demonstrated difficulty with bolus clearance through the oral cavity and pharyngocervical esophagus. Pharyngeal pressures were reduced compared with those of the control subject. While total laryngectomy will stop unremitting aspiration, swallowing after chemoradiation may be severely compromised. This may not be overcome by total laryngectomy.

Osteophyte formation after multilevel anterior cervical discectomy and fusion causing a delayed presentation of functional dysphagia.

BACKGROUND CONTEXT: Anterior cervical discectomy and fusion (ACDF) is a common procedure used to treat radiculopathy and myelopathy from cervical degenerative disc disease. The complications for this procedure are well known. Dysphagia can occur in the postoperative setting. However, it is typically transient and does not last longer than 1 month after an operation. A de novo presentation of dysphagia occurring years after an operation is unique. Osteophyte formation can cause mass effect on the esophagus leading to obstruction of this conduit. However, there have been no reported cases of osteophyte growth fusing to surrounding structures leading to a functional dysphagia. PURPOSE: The authors describe a delayed presentation of functional dysphagia 9 years after an ACDF. This resulted from osteophyte formation originating from the cervical plate and tethering the thyroid cartilage and hyoid bone, thus limiting mobilization of the larynx. STUDY DESIGN/SETTING: Case report. METHODS: The osteophyte was disconnected at the origin of the plate allowing the contents of the neck to move independently. RESULT: After removal of the osteophyte complex at the base of the cervical plate, this patient experienced resolution of his dysphagia. CONCLUSION: Functional dysphagia can occur in a delayed fashion after ACDF from osteophytes tethering the cervical plate to the surrounding contents of the neck used for swallowing. Freeing the contents of the neck from the tethering osteophytes can alleviate symptoms related to a dysfunctional swallowing mechanism.

Advances in surgical management of malignancies of the cranial base: the extended transbasal approach.

The extended transbasal approach combines a bifrontal craniotomy with an orbital nasal and potentially a sphenoethmoidal osteotomy to provide excellent access to malignancies of the anterior, middle and posterior skull base. The approach enables the en bloc resection of tumors within the frontal lobes, orbits, paranasal sinuses and sphenoclival corridors without brain retraction and may obviate the need for transfacial access. We present our 7-year experience during which 29 patients underwent surgery with the extended transbasal exposure. In 25 patients the extended transbasal approach was used alone; in the remaining four it was combined with additional approaches. With exception of two patients, all lesions were removed en bloc. Reconstruction was accomplished with the use of pericranium and in some instances a temporalis muscle pedicle or a gracilis microvascular free flap. There were no mortalities associated with this approach. Seven patients experienced infections, four patients experienced cerebral spinal fluid (CSF) leakage, two patients who had received adjuvant radiation experienced scalp necrosis, three patients experienced pneumocephalus, and 29 patients experienced cranial neuropathies, the majority of which were loss of olfaction. The average follow-up for our patients was 34 months with a range of 2--62 months.

Neck dissection in the combined-modality therapy of patients with locoregionally advanced head and neck cancer.

PURPOSE: The purpose of this study was to evaluate the role of neck lymph node (ND) in the combined dissection modality therapy for locoregionally advanced head and neck. METHODS: We identified patients with N2-N3 head and neck cancers who were enrolled in three consecutive multicenter phase II studies of concurrent chemoradiotherapy utilizing 5-fluorouracil and hydroxyurea on an alternate-week schedule with radiotherapy twice daily plus either cisplatin (C-FHX) or paclitaxel (T-FHX). Patients with unknown primary tumors, nasopharyngeal or paranasal sinus primaries, nonsquamous histology, progression or death during therapy, or incomplete therapy were excluded. RESULTS: A total of 131 patients were analyzed. Seventy-nine percent had N2 stage. ND was performed in 92 patients (70%), either prior to enrollment (n = 31) or after chemoradiotherapy (n = 61). With a median follow-up of 4.6 years, the 5-year locoregional and neck progression-free survival (PFS) rates were higher in patients with ND versus patients without ND: 88% versus 74% (p =.02) and 99% versus 82% (p =.0007). respectively; there was also a trend toward improved overall survival (OS) with ND, but PFS and distant PFS were comparable. In the subset of patients with N3 disease, ND was associated not only with better locoregional control but also with improved distant PFS. However, in patients with clinical complete response (n = 92), no significant differences in PFS (68% vs 75% at 5 years, p =.53) or any other survival parameters with or without ND were observed. CONCLUSIONS: ND improves neck control and is required for patients with clinically residual disease or N3 neck cancer but has no significant impact on the outcome of patients with N2 stage disease who are rendered clinically disease-free with intensive concurrent chemoradiotherapy.

Surgical variables affecting swallowing in patients treated for oral/oropharyngeal cancer.

BACKGROUND: Postoperative swallowing function may be influenced by a number of treatment variables; this study examines the relationship of various treatment factors to measures of swallow function. METHODS: Swallowing was examined with the modified barium swallow procedure in 144 patients surgically treated for oral or oropharyngeal cancer 3 months after healing. Univariate and multivariate correlations were used to examine the relationship between swallowing function and treatment. RESULTS: Percent tongue base resected and total volume resected were most often correlated with swallowing function in the univariate analyses. Multivariate analyses identified the following combinations with the strongest correlations: (1) percent tongue base resected and closure type for liquids; (2) percent tongue base resected and unreconstructed mandible for pastes; (3) total volume resected, percent lateral floor of mouth resected, and postoperative radiotherapy dose for masticated boluses. CONCLUSIONS: Total volume resected and percent tongue base resected had a profound impact on postoperative swallowing function. Combinations of percent tongue base resected with other surgical variables had the strongest relationships with overall swallowing function.