Richard L. Scher

Hyperfractionated Irradiation with or without Concurrent Chemotherapy for Locally Advanced Head and Neck Cancer

BACKGROUND Radiotherapy is often the primary treatment for advanced head and neck cancer, but the rates of locoregional recurrence are high and survival is poor. We investigated whether hyperfractionated irradiation plus concurrent chemotherapy (combined treatment) is superior to hyperfractionated irradiation alone. METHODS Patients with advanced head and neck cancer who were treated only with hyperfractionated irradiation received 125 cGy twice daily, for a total of 7500 cGy. Patients in the combined-treatment group received 125 cGy twice daily, for a total of 7000 cGy, and five days of treatment with 12 mg of cisplatin per square meter of body-surface area per day and 600 mg of fluorouracil per square meter per day during weeks 1 and 6 of irradiation. Two cycles of cisplatin and fluorouracil were given to most patients after the completion of radiotherapy. RESULTS Of 122 patients who underwent randomization, 116 were included in the analysis. Most patients in both treatment groups had unresectable disease. The median follow-up was 41 months (range, 19 to 86). At three years the rate of overall survival was 55 percent in the combined-therapy group and 34 percent in the hyperfractionation group (P=0.07). The relapse-free survival rate was higher in the combined-treatment group (61 percent vs. 41 percent, P=0.08). The rate of locoregional control of disease at three years was 70 percent in the combined-treatment group and 44 percent in the hyperfractionation group (P=0.01). Confluent mucositis developed in 77 percent and 75 percent of the two groups, respectively. Severe complications occurred in three patients in the hyperfractionation group and five patients in the combined-treatment group. CONCLUSIONS Combined treatment for advanced head and neck cancer is more efficacious and not more toxic than hyperfractionated irradiation alone.

Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck

PURPOSE Tumor hypoxia adversely affects short term clinical radiation response of head and neck cancer lymph node metastases and long term disease-free survival (DFS) in cervix carcinoma. This study was performed to evaluate the relationship between tumor hypoxia and DFS in patients with squamous carcinoma of the head and neck (SCCHN). METHODS AND MATERIALS Pretreatment tumor pO2 was assessed polarographically in SCCHN patients. All patients were AJCC Stage IV and had pretreatment oxygen measurements taken from locally advanced primaries (T3 or T4) or neck nodes > or = 1.5 cm diameter. Treatment consisted of once daily (2 Gy/day to 66-70 Gy) or twice daily irradiation (1.25 Gy B.I.D. to 70-75 Gy) +/- planned neck dissection (for > or = N2A disease) according to institutional treatment protocols. RESULTS Twenty-eight patients underwent tumor pO2 measurement. The average pre-treatment median pO2 was 11.2 mm Hg (range 0.4-60 mm Hg). The DFS at 12 months was 42%. The DFS was 78% for patients with median tumor pO2 > 10 mm Hg but only 22% for median pO2 < 10 mm Hg (p = 0.009). The average tumor median pO2 for relapsing patients was 4.1 mm Hg and 17.1 mm Hg in non-relapsing (NED) patients (p = 0.007). CONCLUSION Tumor hypoxia adversely affected the prognosis of patients in this study. Understanding of the mechanistic relationship between hypoxia and treatment outcome will allow for the development of new and rational treatment programs in the future.

Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer

PURPOSE Hypoxia shifts the balance of cellular energy production toward glycolysis with lactate generation as a by-product. Quantitative bioluminescence imaging allows for the quantitation of lactate concentrations in individual tumors. We assessed the relationship between pretreatment tumor lactate concentrations and subsequent development of metastatic disease in patients with newly diagnosed head-and-neck cancer. METHODS AND MATERIALS At the time of biopsy of the primary site, a separate specimen was taken and flash-frozen for subsequent quantitation of lactate concentration using a luciferase bioluminescence technique. The two-dimensional spatial distribution of the bioluminescence intensity within the tissue section was registered directly using a microscope and an imaging photon counting system. Photon intensity was converted to distributions of volume-related tissue concentrations (micromol per gram wet weight). Treatment consisted of either surgery and postoperative radiotherapy or primary radiotherapy, based on presenting disease stage and institutional treatment policies. The subsequent development of metastatic disease constituted the primary clinical endpoint. RESULTS Biopsies obtained from 40 patients were evaluable in 34. The larynx was the most frequent primary site (n = 25). Other sites included oropharynx (n = 5), hypopharynx (n = 3), and oral cavity (n = 1). Most patients (74%) presented with an advanced stage T3 or T4 primary tumor. Nodal involvement was present in 19 (54%) patients. The median tumor lactate concentration was 7.1 micromol/g. Tumors were classified as having either low or high lactate concentrations according to whether these values were below or above the median. The median follow-up time for surviving patients is 27 months. Two-year actuarial survival was 90% for patients with low-lactate-concentration tumor vs. 35% for patients with high-lactate-concentration primaries (<0.0001). Two-year metastasis-free survival was adversely influenced by high tumor lactate concentrations (90% vs. 25%, p < 0.0001). The median lactate concentration for tumors that subsequently metastasized was 12.9 micromol/g vs. 4.8 micromol/g for patients who remained continuously free of disease (p < 0.005). Lactate concentration was not correlated with presenting T stage or N stage. DISCUSSION Elevated tumor lactate concentrations are associated with the subsequent development of nodal or distant metastases in head-and-neck cancer patients. This more aggressive malignant phenotype is probably associated with hypoxia-mediated radioresistance and the upregulation of metastasis-associated genes.

Endoscopic Staple Diverticulostomy for Zenker's Diverticulum: Review of Literature and Experience in 159 Consecutive Cases

Objectives/Hypothesis Several reports since the early 1990s have advocated a minimally invasive technique, endoscopic staple diverticulostomy (ESD), to treat Zenkers diverticulum. However, long‐term results and comparisons with the reported experience with external or other endoscopic approaches have been lacking in the literature. We present follow‐up on our experience with ESD since 1995 and compare it with the results obtained by other endoscopic or external techniques for treatment of Zenkers diverticulum.

Endoscopic Staple‐Assisted Esophagodiverticulostomy for Zenker's Diverticulum

We have used a new technique, endoscopic staple‐assisted esophagodiverticulostomy (ESED), for the treatment of Zenkers diverticulum. This technique is a modification of the endoscopic approach first described by Mosher 1 in 1917 and popularized by Dohlman and Mattsson 2 in which the common wall between the esophagus and diverticulum was divided without mucosal closure. ESED differs in that an endosurgical stapler is used to create an esophagodiverticulostomy by dividing the common wall between the esophagus and diverticulum, with the mucosal and muscular edges sealed by the staples. We have performed this procedure in six patients, with no perioperative morbidity in any patient. All patients resumed oral intake on either the first or second postoperative day, with no evidence of fistula formation or mediastinitis. Hospital stay has averaged 2 days (range, 1 to 3 days). Patient follow‐up after ESED averages 6 months and is available for five of the six patients treated. There has been complete resolution of pretreatment symptoms in these five patients, with resumption of regular diet between postoperative day 3 and day 14 (average, day 9). Our results demonstrate that ESED is a safe and effective treatment for Zenkers diverticulum. This endoscopic approach offers a number of advantages over previously used treatments for Zenkers diverticulum, including reduced morbidity, rapid convalescence, short hospitalization, brief operative time, and predictable resolution of symptoms.

Endoscopic Staple-Assisted Esophagodiverticulostomy: An Excellent Treatment of Choice for Zenker's Diverticulum†

Objectives The objectives of the present study are to review the technique of endoscopic staple‐assisted esophagodiverticulostomy (ESED) for the treatment of Zenkers diverticulum and to describe our e‐perience and modifications with ESED and the advantages of ESED over previous treatments of Zenkers diverticulum.

Preoperative radiotherapy and bevacizumab for angiosarcoma of the head and neck: Two case studies

Angiosarcoma of the face is a vascular tumor with poor local control and short median survival despite standard treatment. Bevacizumab is a humanized monoclonal antibody to vascular endothelial growth factor (VEGF), which can inhibit tumor growth. It is synergistic with radiotherapy in gastrointestinal malignancies. Given the vascular nature of angiosarcoma and the need for better treatment of this disease, we investigated the concurrent use of bevacizumab with preoperative radiotherapy for head and neck angiosarcoma.

Treatment of Cervical Necrotizing Fasciitis with Hyperbaric Oxygen Therapy

Hyperbaric oxygen therapy has significantly improved the management of necrotizing fasciitis of the extremities and trunk. Its role in cervical necrotizing fasciitis has not been fully evaluated. Historically, necrotizing fasciitis has been associated with considerable morbidity and mortality. This report discusses our experience with cervical necrotizing fasciitis in six patients treated from 1986 to 1993 who received hyperbaric oxygen therapy. All patients survived. In all cases infection was of probable odontogenic origin. Most patients in whom necrotizing fasciitis develops have identifiable risk factors; however, two patients in this series were previously healthy, and there was no relationship between hospital course and identified risk factors. Clinical presentation and microbiology are reviewed together with the rationale for hyperbaric oxygen therapy as an adjunct to broad-spectrum antibiotics and aggressive early surgical debridement.

Prospective Trial of Synchronous Bevacizumab, Erlotinib, and Concurrent Chemoradiation in Locally Advanced Head and Neck Cancer

Purpose: We assessed the safety and efficacy of synchronous VEGF and epidermal growth factor receptor (EGFR) blockade with concurrent chemoradiation (CRT) in locally advanced head and neck cancer (HNC). Experimental Design: Newly diagnosed patients with stage III/IV HNC received a 2-week lead-in of bevacizumab and/or erlotinib, followed by both agents with concurrent cisplatin and twice daily radiotherapy. Safety was assessed using Common Toxicity Criteria version 3.0. The primary efficacy endpoint was clinical complete response (CR) rate after CRT. Results: Twenty-nine patients enrolled on study, with 27 completing therapy. Common grade III toxicities were mucositis (n = 14), dysphagia (n = 8), dehydration (n = 7), osteoradionecrosis (n = 3), and soft tissue necrosis (n = 2). Feeding tube placement was required in 79% but no patient remained dependent at 12-month posttreatment. Clinical CR after CRT was 96% [95% confidence interval (CI), 82%–100%]. Median follow-up was 46 months in survivors, with 3-year locoregional control and distant metastasis-free survival rates of 85% and 93%. Three-year estimated progression-free survival, disease-specific survival, and overall survival rates were 82%, 89%, and 86%, respectively. Dynamic contrast enhanced MRI (DCE-MRI) analysis showed that patients who had failed had lower baseline pretreatment median Ktrans values, with subsequent increases after lead-in therapy and 1 week of CRT. Patients who did not fail had higher median Ktrans values that decreased during therapy. Conclusions: Dual VEGF/EGFR inhibition can be integrated with CRT in locally advanced HNC, with efficacy that compares favorably with historical controls albeit with an increased risk of osteoradionecrosis. Pretreatment and early DCE-MRI may prospectively identify patients at high risk of failure. Clin Cancer Res; 18(5); 1404–14. ©2012 AACR.

The craniofacial resection--eleven-year experience at the University of Virginia: problems and solutions.

From September 1976 to December 1987, 25 patients underwent 27 craniofacial resections at the University of Virginia Health Sciences Center. Two of these patients, who had recurrent disease Involving the cavernous sinus, underwent repeat, extended resections. Seventeen of the tumors were esthesloneuroblastomas. Only one patient had received no treatment before surgery. The complications of this surgical technique are reviewed. The most significant complications were neurologic problems and Infection. Additional issues, such as the handling of the eye, lacrimal sac, and medial canthal ligament, are also reviewed.