Final results of a multi-institutional phase II trial of reirradiation with concurrent weekly cisplatin and cetuximab for recurrent or second primary squamous cell carcinoma of the head and neck.

Background: The optimal regimen of chemotherapy and reirradiation (re-XRT) for recurrent head and neck squamous cell carcinoma (HNSCC) is controversial. We report the final outcomes of a multicenter phase II trial evaluating cetuximab and cisplatin-based chemotherapy concurrent with re-XRT for patients with recurrent HNSCC. Materials and methods: Patients with unresectable recurrent disease or positive margins after salvage surgery arising within a previously irradiated field with KPS ≥ 70 were eligible for this trial. Cetuximab 400 mg/m2 was delivered as a loading dose in week 1 followed by weekly cetuximab 250 mg/m2 and cisplatin 30 mg/m2 concurrent with 6 weeks of intensity-modulated radiotherapy to a dose of 60-66 Gy in 30 daily fractions. Patients who previously received both concurrent cetuximab and cisplatin with radiation or who received radiotherapy less than 6 months prior were ineligible. Results: From 2009 to 2013, 48 patients enrolled on this trial, 2 did not receive any protocol treatment. Of the remaining 46 patients, 34 were male and 12 female, with a median age of 62 years (range 36-85). Treatment was feasible and only 1 patient did not complete the treatment course. Common grade 3 or higher acute toxicities were lymphopenia (46%), pain (22%), dysphagia (13%), radiation dermatitis (13%), mucositis (11%) and anorexia (11%). There were no grade 5 acute toxicities. Eight grade 3 late toxicities were observed, four of which were swallowing related. With a median follow-up of 1.38 years, the 1-year overall survival (OS) was 60.4% and 1-year recurrence-free survival was 34.1%. On univariate analysis, OS was significantly improved with young age (P = 0.01). OS was not associated with radiation dose, surgery before re-XRT or interval from prior XRT. Conclusions: Concurrent cisplatin and cetuximab with re-XRT is feasible and offers good treatment outcomes for patients with high-risk features. Younger patients had significantly improved OS. ClinicalTrials.Gov Identifier: NCT00833261.

Posterior scleritis with annular ciliochoroidal detachment.

PURPOSE: We studied an unusual case of posterior scleritis in a patient with sarcoidosis. METHOD: The medical record was reviewed for clinical manifestation, course, and tests performed, including laboratory evaluations, fluorescein angiography, and ultrasonography. RESULTS: The patient had posterior scleritis and unilateral angle-closure glaucoma caused by an annular ciliochoroidal detachment. Sarcoidosis was confirmed by biopsy of an enlarged parotid gland. CONCLUSION: The mechanism of angle-closure glaucoma may not be clinically or echographically apparent for a week or more in patients who develop annular ciliochoroidal detachment. We also found an unusual association of sarcoidosis and annular ciliochoroidal detachment secondary to posterior scleritis.

Aggressive fibromatosis of the prevertebral and retropharyngeal spaces: MR and CT characteristics.

A 47-year-old man had aggressive fibromatosis, and CT and MR showed a large, multilobulated soft-tissue mass within the prevertebral and retropharyngeal spaces. On CT, the lesion was slightly higher in attenuation than adjacent muscle; on MR, it was intermediate between muscle and fat on unenhanced T1-weighted images, isointense with fat on intermediate-weighted images, hyperintense relative to fat on T2-weighted images, and markedly enhanced after administration of gadopentetate dimeglumine. Multiple small focal and linear areas of decreased signal intensity that did not enhance with gadopentetate dimeglumine were observed on all pulse sequences.

Multiple myeloma involving the thyroid cartilage.

Extraosseous multiple myeloma involving the larynx is rare. We describe a patient with multiple myeloma and a plasmacytoma involving the thyroid cartilage. Ossification of the thyroid cartilage with formation of a marrow space could explain the occurrence of multiple myeloma in this unusual location.

The AO system for primary mandibular reconstruction.

We reviewed the records of 27 patients who underwent primary mandibular reconstruction with AO plates to investigate the outcome and complications of this procedure. Immediate soft-tissue flap coverage was required in 26 patients. Early complications were seen in 44% of the patients, with the highest incidence after irradiation (P = 0.02). Late complications were mostly related to tumor recurrence (12). Late complications not associated with recurrence were persistent pain (2), minor infections (3), plate exposure (3), and plate fracture (1). Good to excellent cosmetic results were obtained in all but 1 patient. Full mastication was not possible for any of our patients, and therefore function was not fully restored. Speech and deglutition were mostly influenced by the amount of soft-tissue resection. Mean follow-up was 20 months (range 3 to 52). At last evaluation, 12 patients were alive and free of disease, and 15 were dead of disease or other causes. Our results show that primary mandibular reconstruction with rigid plates is a safe, effective, and reliable technique to restore mandibular continuity and cosmesis. For lateral defects, this method is a viable alternative to free vascularized osseocutaneous flaps.

P53 and Ki-67 as outcome predictors for advanced squamous cell cancers of the head and neck treated with chemoradiotherapy.

HYPOTHESIS: P53 and Ki-67 status will predict response to treatment, organ preservation, and survival in patients with advanced squamous cell cancers of the head and neck treated with chemoradiotherapy (CRT). STUDY DESIGN: Retrospective analysis of p53 and Ki-67 status from the CRT arm of a randomized, controlled trial (n = 50) and from patients receiving the same treatment but not enrolled in the trial (n = 55). METHODS: P53 and Ki-67 status were established from archived tissue samples using immunohistochemical (IHC) staining. Tumors were positive for p53 (p53+) when more than 2% of cells stained for p53 and were positive for Ki-67 (Ki-67+) when any cell stained for Ki-67. End points were tumor response, tumor recurrence, survival status, and organ preservation at last follow-up, and time to events. Predictive models were calculated for each outcome. RESULTS: Neither marker predicted tumor response to treatment. P53+ status was associated with tumor recurrence (P =.003) and locoregional recurrence (P =.003). Adjusting for time to event, p53+ status was significantly related to a lower recurrence-free survival (P =.004), lower disease-specific survival (P =.04), lower overall survival with primary site preservation (P =.03), and lower disease-specific survival with primary site preservation (P =.003). Multivariate analysis revealed that p53+ status was significantly related to a lower recurrence-free survival (P =.01, risk ratio [RR] = 3.65) and lower disease-specific survival with organ preservation (P =.02, RR = 3.41). Ki-67+ status was not related to any variables. However, multivariate analysis revealed that Ki-67+ was significantly related to a lower overall survival (P =.05, RR = 2.03). The combination of both markers negative (p53-/Ki-67-) was associated with a lower incidence of tumor recurrence (P =.02), lower locoregional recurrence (P =.01), and fewer second primary lesions (P =.04). Adjusting for time to event, p53-/Ki-67- status was significantly related to a higher recurrence-free survival (P =.02), higher disease-specific survival with primary site preservation (P =.02), and higher overall survival with primary site preservation (P =.02). Multivariate analysis revealed that p53-/Ki-67- status was significantly related to a higher overall survival with site preservation (P =.01, RR = 2.78). CONCLUSIONS: P53 and Ki-67 status appear to be related to the various survival end points considered in this study. However, this relation does not seem to be sufficient to warrant treatment modifications. Closer follow-up may be justified in both p53+ and Ki67+ patients to detect recurrence or a second primary at an earlier stage, possibly improving survival.

Surgical outcome in 87 patients with Zenker's diverticulum.

Surgical treatment of Zenker's diverticulum is controversial because many different procedures exist. We retrospectively reviewed 87 consecutive patients surgically treated for Zenker's diverticulum at a tertiary care institution from 1976 through 1993. Four surgical procedures were performed: cricopharyngeal myotomy alone (n = 16), excision (hand-sewn) plus myotomy (n = 51), excision (stapler) plus myotomy (n = 11), and diverticulopexy plus myotomy (n = 9). There were three surgical mortalities (3.5%) and a complication rate of 24%. Eighty patients (92%) were available for follow up. Sixty-eight patients (78%) reported excellent relief of symptoms, 10 (13%) reported improvement with occasional symptoms, and two (3%) described persistent dysphagia. No statistical difference in complication rate was found among surgical groups (P = 0.15). Myotomy alone patients had worse outcomes (P = 0.04) compared with the other surgical groups. Median follow-up was 7.5 months.

Rigid endoscopic repair of paranasal sinus cerebrospinal fluid fistulas.

The advent of functional transnasal endoscopic sinus surgery has brought new opportunities in the repair of difficult cerebrospinal fluid leaks of the paranasal sinuses. The following four case reports illustrate the repair of cerebrospinal fluid leaks with the use of rigid transnasal endoscopy for enhanced angled visualization and illumination. A description of surgical techniques and instrumentation involving transnasal endoscopy in repair of sphenoidal and ethmoidal cerebrospinal fluid fistulas is reported. A discussion of etiology, diagnoses, and conservative versus surgical management of cerebrospinal fluid rhinorrhea is presented.

Complementary use of computed tomography and magnetic resonance imaging in assessing skull base lesions.

Twenty-six patients underwent computed tomography (CT) and magnetic resonance imaging (MRI) of skull base lesions at the Cleveland Clinic Foundation. CT provided improved bone detail, documenting invasion of the lamina papyracea, orbital floor, fovea ethmoidalis, cribriform plate, pterygoid plates, hard palate, and skull base. MRI defined invasion of the orbit, dura, brain, and cavernous sinus. Improved soft-tissue-tumor interface was evident on MRI. MRI was superior to CT in determining carotid artery involvement. MRI distinguished between tumor and retained secretions in the paranasal sinuses. Combining radiographic tumor staging reliably predicted surgical findings; however, MRI consistently yielded sufficient diagnostic information and the additional expense of performing two imaging procedures may not be justified.

Lymphoma of the parotid gland.

In a consecutive group of 452 patients undergoing parotid surgery at this institution, 18 (4%) were found to have lymphoma. Review and analysis of presenting symptoms, predisposing factors, histopathology, postsurgical morbidity, and long-term outcome with treatment are presented. The current literature on parotid lymphoma is reviewed, and management strategies are outlined. Although a relatively uncommon primary lesion, lymphoma must be considered in the differential diagnosis of any mass presenting in the parotid gland.

Impact of steroids on recovery after uvulopalatopharyngoplasty.

OBJECTIVE: To determine whether perioperative systemic corticosteroid administration can reduce uvulopalatopharyngoplasty (UPPP) postoperative morbidities (e.g., pain, anorexia, sleep disturbance, mouth odor, and fatigue) or reduce narcotic analgesic usage. STUDY DESIGN: A prospective, double-blinded study with random assignment of treatment agent (placebo or corticosteroid). METHODS: From 1995 to 1998, a consecutive sample of 48 adults presenting for elective UPPP surgery alone or in combination with tonsillectomy or septoplasty, or both, were enrolled. Twenty-eight subjects completed the protocol and were equally distributed by random assignment to intramuscular (IM) and intravenous (IV) doses of placebo (saline) or corticosteroid (60 mg methylprednisolone IM and 12 mg dexamethasone IV). Acetaminophen with codeine analgesic was available to both groups as needed. Subjects recorded a diary of symptom severity scores over the first postoperative week relating to eight commonly reported morbidities (1-4 points) and the daily quantity of narcotic consumed. RESULTS: Statistical comparison (Wilcoxon's rank sum test) showed no significant differences between subjects treated with placebo or corticosteroid on postoperative day 1 or 7. Three subjects (21%) in each treatment group reported no postoperative use of narcotic analgesic. CONCLUSIONS: No statistically or clinically significant benefits were derived from perioperative systemic corticosteroid treatment in this sample of 28 adults treated with UPPP alone or in combination with tonsillectomy or septoplasty, or both. Some individuals tolerate post-UPPP discomfort without a narcotic analgesic.

Squamous cell carcinoma of the paranasal sinuses: the Cleveland Clinic experience 1977-1986.

Fifty-four of 103 malignancies of the paranasal sinuses treated at the Cleveland Clinic Foundation between 1977 and 1986 were squamous cell carcinomas. Six arose from the ethmoid sinus and 48 from the maxillary sinus. Of the maxillary sinus patients, 11 presented with T1 or T2 lesions, 20 with T3, 16 with T4, and 7 of these had nodal disease. Treatment was surgery and/or radiation therapy. There was local recurrence in 25 of 48 maxillary sinus patients and in 1 of 6 ethmoid patients. Overall 5-year survival was 38.2% in the maxillary sinus group: T1, 100.0%; T2, 85.7%; T3, 31.8%; and T4, 6.7%. Three of six patients with ethmoid tumors were cured. There was a statistical trend for better prognosis in those patients presenting with ethmoid primaries, with early lesions, treated with both radiation and surgery, and with history of inverting papilloma. There were complications of treatment in 10 patients, four of which resulted in death. Local control was the major problem for these patients; therefore, early detection and aggressive local treatment are desirable.

Facial nerve morbidity following parotid surgery for benign disease: the Cleveland Clinic Foundation experience.

Standard surgical management for benign tumors of the parotid gland requires either superficial, subtotal, or total parotidectomy with preservation of the facial nerve. Although this approach is effective in minimizing recurrence, the resultant facial nerve morbidity is seldom addressed. Two hundred fifty-six consecutive patients who underwent parotid surgery for benign neoplasia at this institution in the past 15 years are reviewed, with attention to postoperative facial nerve function. Immediate dysfunction was frequently encountered (46.1%), but permanent dysfunction was uncommon (3.9%). The incidence of long-term dysfunction may be higher in revision cases and when an extended (total or subtotal) parotidectomy is performed.

Polymyositis presenting as a neck mass.

Polymyositis is a rare disease entity belonging to the class of enigmatic disorders known as the collagen vascular diseases. It is characterized by proximal muscle weakness. More than 50% of the patients with this disease have development of head and neck manifestations, most commonly a heliotrope rash or dysphagia. Weakness and atrophy of neck muscles, and lolling of the neck have also been described. We report a case of polymyositis presenting as a neck mass, a heretofore undescribed manifestation of this disease in the head and neck. A review of the literature and an interdisciplinary approach to the diagnosis and management of this unusual disease will be described.

Extranodal lymphomas of the head and neck. A 20-year experience.

BACKGROUND: Extranodal non-Hodgkin lymphoma (NHL) of the head and neck is a relatively uncommon disease. Over the last 3 decades, a variety of systems, including the Rappaport, Luke-Collins, and Working Formulation classifications, have been used to classify extranodal NHLs of the head and neck. Most studies have included a relatively small number of patients, used different modalities of therapy, and did not include all head and neck sites. These limitations make comparisons between different studies and drawing any conclusions difficult. OBJECTIVES: To describe in a uniform fashion a relatively large number of patients with extranodal NHL of the head and neck treated at the same institution, using only the most current classification system and to describe the clinical features, behavior, and outcome of this relatively uncommon, but potentially curable disease. DESIGN: A retrospective study of 98 patients with extranodal NHL of the head and neck. All patients were reclassified according to the Working Formulation system (regardless of the time of diagnosis) in order to uniformly define the clinical course of this disease in the head and neck. SETTING: A tertiary care referral center. RESULTS AND CONCLUSIONS: The sinonasal tract was the most commonly involved site (25%). If the nasopharynx (16%), tonsil (12%), and base of tongue (8%) are grouped together, this combined site (Waldeyer ring) becomes the most common site of disease (36%). Patients with tonsillar lymphoma had a 20% incidence of associated gastrointestinal involvement. Approximately 50% of the patients had associated nodal disease, and only 20% had systemic or B symptoms. Three fourths of the patients had stage I or II disease, and approximately two thirds had intermediate-grade lymphoma. Radiation therapy was the primary modality of therapy for localized disease (stages I and II), especially for low-grade lymphomas. Combination chemotherapy with or without radiation was used for more advanced disease and for intermediate- and high-grade lymphomas. Surgery was limited to establishing the diagnosis. Two thirds of the patients had a remission after initial therapy. Two thirds of these patients had no further relapse. Three fourths of the patients with relapse after initial remission died of their disease. The overall and disease-free survival rates for all patients were 60% and 50%, respectively. Outcome of therapy was related to stage and histologic grade. Patients with lymphomas of high histopathologic grade and recurrent and recurrent and disseminated disease had the poorest prognosis.

Secondary tracheoesophageal puncture for voice rehabilitation after laryngectomy.

Since the introduction of the tracheoesophageal puncture technique for restoration of voice in 1980, 125 secondary punctures have been performed in 117 patients at the Cleveland Clinic Foundation. Preoperative evaluation, pharyngeal preparation, and their relation to final speech results were reviewed retrospectively. Critical factors in the rehabilitation of these patients are discussed based on our experience and a review of the literature.

Factors influencing survival in ethmoid sinus cancer.

Nineteen patients with primary ethmoid sinus malignancies were treated at the Cleveland (Ohio) Clinic Foundation between 1976 and 1989. Pathologic diagnoses included adenocarcinoma (eight), sarcoma (four), squamous cell carcinoma (three), mucoepidermoid carcinoma (two), adenoid cystic carcinoma (one), and undifferentiated carcinoma (one). All patients underwent surgical resection: 13 had craniofacial resection, four had craniofacial resection/orbital exenteration, one had radical ethmoidectomy/maxillectomy/orbital exenteration, and one had transantral ethmoidectomy. Twelve patients had combined treatment with radiation therapy. Ten patients were alive with no evidence of disease. A trend toward improved prognosis is associated with negative surgical margins. Preservation of the globe was not associated with local recurrence at this site. A poor prognosis was noted with involvement of the dura, brain, nasopharynx, or sphenoid sinus.

Comparison of surgical complications after organ-preservation therapy in patients with stage III or IV squamous cell head and neck cancer.

OBJECTIVE: To determine the incidence of minor and major complications in patients with squamous cell carcinoma of the upper aerodigestive tract who require surgical salvage or planned neck dissection after an initial treatment regimen with radiotherapy or concurrent chemoradiotherapy for organ preservation. DESIGN: The medical records of 100 patients treated in a phase 3 trial comparing radiotherapy alone with concurrent chemoradiotherapy for stage III and IV head and neck squamous cell carcinoma were reviewed. Fifty-four patients underwent 59 surgical procedures. Twenty-nine planned neck dissections were performed for persistent neck disease or initial stage N2 or greater. For persistent or recurrent disease at the primary site, 30 salvage operations were performed. SETTING: Academic tertiary care referral center. RESULTS: Complications occurred in 15 (46%) of the 33 procedures in the radiation-only group and 12 (46%) of the 26 procedures in the chemoradiotherapy group. Major complications occurred in 4 (12%) of the procedures in the radiation-only group and 3 (12%) of the procedures in the chemoradiotherapy group. The incidence of minor complications was 33% and 35% in the radiation-only and chemoradiotherapy groups, respectively. The major complication rate for salvage operations did not differ between the radiation-only and chemoradiotherapy groups (16% and 27%, respectively; P=.79 by chi2 test). The incidence of major complications in planned neck dissections was 7% of the radiation-only group and 0% of the chemoradiotherapy group. CONCLUSIONS: After radiation or concurrent chemoradiotherapy, surgery can be performed with an acceptable rate of major complications. Adding chemotherapy did not increase the incidence of surgical complications. These results differ from other reports in the literature.

Aggressive concurrent chemoradiotherapy for squamous cell head and neck cancer: an 8-year single-institution experience.

BACKGROUND: Since 1989, 105 patients with squamous head and neck cancer have been treated with combined chemoradiotherapy. OBJECTIVE: To examine the effectiveness of using combined chemoradiotherapy on patients with squamous head and neck cancer. DESIGN: Eight-year (1989-1997) single-institution evaluation of 105 patients. METHODS: Treatment consisted of fluorouracil, 1000 mg/m2 per day, and cisplatin, 20 mg/m2 per day, both given as continuous infusions during 4 days beginning on day 1 and 22 of a concurrent radiotherapy course. Radiation was given in single daily fractions of 1.8 to 2 Gy, to a total dose of 66 to 72 Gy. Salvage surgery was performed for any residual or recurrent locoregional disease. Planned neck dissection was recommended for all patients with N2+ neck disease, irrespective of clinical response. RESULTS: The 105-patient cohort consisted of 79 men and 26 women. The primary site was identified in the oral cavity in 6, oropharynx in 46, larynx in 30, and hypopharynx in 20 patients. Two patients had multiple primaries and 1 patient had an unknown primary. There were 4 patients with stage II, 24 with stage III, and 77 with stage IV disease. Grade 3 and 4 chemoradiotherapy toxic effects included mucositis in 88% of patients, cutaneous reaction in 50%, neutropenia in 49%, thrombocytopenia in 12%, and nausea in 5%. There were no deaths secondary to treatment. The mean weight loss was 12% of initial body weight. To date, primary site persistence or recurrence has occurred in only 14 patients (13%). With a mean follow-up of 39 months, 66 patients (63%) are alive and free of disease. The Kaplan-Meier 4-year projected overall survival is 60% with a disease-specific survival of 74%, a distant metastasis-free survival of 84%, and an overall survival with primary site preserved of 54%. CONCLUSIONS: This chemoradiotherapy regimen, although toxic, is tolerable with appropriate supportive intervention. Locoregional and distant control are likely. Primary site conservation is possible in most patients. Chemoradiotherapy appears to have an emerging role in the primary management of head and neck cancer.

Systemic adoptive T-cell immunotherapy in recurrent and metastatic carcinoma of the head and neck: a phase 1 study.

OBJECTIVE: To evaluate the feasibility and toxic effects of systemic adoptive T-cell immunotherapy in patients with unresectable squamous cell carcinoma of the head and neck (SCCHN). DESIGN: Nonrandomized phase 1 clinical trial. SETTING: Academic tertiary care hospital. PATIENTS: Between April 1, 1996, and September 30, 1998, 17 patients with confirmed recurrent and metastatic SCC of the upper aerodigestive tract were enrolled. Two patients did not receive T cells because of poor vaccine response. Fifteen patients were successfully treated with T-cell immunotherapy. INTERVENTION: Patients were vaccinated on the thigh with irradiated autologous tumor cells admixed with granulocyte-macrophage colony-stimulating factor (GM-CSF) followed by 3 additional daily injections of GM-CSF at the vaccination site. Eight to 10 days later, tumor cell vaccine-draining inguinal lymph nodes were resected, and lymph node lymphocytes were activated with staphylococcal enterotoxin A and expanded in interleukin 2 in vitro. Resulting cultured cells were infused into patients peripherally on an outpatient basis. RESULTS: Toxic effects of infusion were limited to grade 2 reactions in 3 of 16 treatments. One patient required overnight hospitalization for fever and emesis. Median cell expansion was 37 times (range, 4-416 times), and median cell dose was 7.5 x 10(9) (range, 1.3 x 10(8) to 4.2 x 10(10)). Infused cells were predominantly CD3+ (>97%), being a mixture of CD4+ and CD8+ cells. Three patients demonstrated stabilization of previously progressive disease. Two patients experienced favorable clinical courses after adoptive T-cell transfer, including 1 patient with no evidence of disease 4 years after surgical resection of a vertebral body metastasis. CONCLUSIONS: Adoptive immunotherapy is a technically feasible and safe treatment with low toxicity and may demonstrate therapeutic activity in patients with unresectable SCCHN.