Louis G. Portugal

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.

Concomitant Infusional Paclitaxel and Fluorouracil, Oral Hydroxyurea, and Hyperfractionated Radiation for Locally Advanced Squamous Head and Neck Cancer

PURPOSE To improve local disease control and survival with organ preservation, we conducted a phase II multi-institutional trial with a concomitant taxane-based chemotherapy and hyperfractionated radiation regimen. PATIENTS AND METHODS Sixty-four patients with locally advanced squamous cancers (stage IV, 98%; N2/3, 81%) were treated on an intensive regimen consisting of 5-day (120-hour) infusions of paclitaxel (20 mg/m(2)/d) and fluorouracil (600 mg/m(2)/d), oral hydroxyurea 500 mg every 12 hours for 11 doses, and radiation 1.5 Gy bid (T-FH2X). Chemoradiation was administered concomitantly on days 1 to 5 of each 14-day cycle. A full treatment course consisted of five cycles during a 10-week period to a total radiation dose of 72 to 75 Gy. RESULTS The median follow-up for the group is 34 months. At 3 years, progression-free survival is 63%, locoregional control is 86%, and systemic control is 79%; overall survival is 60%. Seventeen patients died of recurrent cancer, two died of second primary cancers, and four died of other causes. Side effects observed include anemia (22% required transfusion), leucopenia (34%, grade 3 to 4), and mucositis (84%, grade 3 to 4). Organ preservation principles were maintained. At 1 year posttreatment, 61% of patients had severe xerostomia and 47% had compromised swallowing. There was little disturbance of speech quality in 97% of patients at the same follow-up point. CONCLUSION T-FH2X is a highly active and tolerable concomitant chemotherapy and hyperfractionated radiation regimen that induces sustained local tumor control and holds promise for improved survival with organ preservation in high-risk patients. Identification of less toxic therapy and improved distant disease control are needed. T-FH2X should be tested in a randomized trial and compared with a less intensive concomitant regimen that uses once-daily radiation fractionation.

Salvage treatment for recurrent squamous cell carcinoma of the oral cavity.

Squamous cell carcinoma (SCCA) of the oral cavity recurs with a frequency of 25%–48%, a fact that usually portends a poor prognosis. Recent studies have reported salvage cure rates as high as 67%. Investigators have also claimed that restaging recurrent tumors provides useful prognostic information, although this has not been demonstrated with tumors of the oral cavity. The purposes of this study were: (1) to report the patterns of recurrent SCCA of the oral cavity; (2) to examine the benefit of restaging oral cavity tumors, and (3) to compare different treatment modalities in the management of recurrent SCCA of the oral cavity.

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

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.

Prior chemoradiotherapy adversely impacts outcomes of recurrent and second primary head and neck cancer treated with concurrent chemotherapy and reirradiation.

It has been shown that concomitant chemotherapy (C) with reirradiation (ReRT) is feasible and effective for select patients with recurrent or second primary head and neck cancer (HNC). To examine potential prognostic factors associated with survival, the authors of this report retrospectively reviewed the outcomes of patients who received CReRT.

Prognostic Indicators for Squamous Cell Carcinoma of the Oral Cavity: A Clinicopathologic Correlation†

Fifty‐three patients with T1 squamous cell cancer of the floor of mouth and ventral surface of the tongue with a known clinical outcome were retrospectively analyzed and arbitrarily divided into “aggressive” and “nonaggressive” groups based on their clinical behavior. Various host and tumor factors were then evaluated in an attempt to determine whether the tumor behavior could have been predicted. The paraffin‐embedded tumor specimens were evaluated for tumor differentiation, tumor thickness and tumor invasion, microvessel density, and p53 expression. In addition, a composite morphologic grading score was obtained by combining cell differentiation, nuclear polymorphism, mitosis activity, depth of infiltration, type of infiltration, and lymphatic infiltration. No single technique appeared capable of identifying “aggressive” behavior, although possibly an evaluation of composite factors might show promise in the future.

Negative-pressure pulmonary edema in the otolaryngology patient☆☆☆

It is estimated that 11% of all patients requiring active intervention for acute upper airway obstruction develop negative-pressure pulmonary edema. This pathologic process typically has a benign and rapidly resolving clinical course with the prompt use of mechanical ventilation and positive end expiratory pressure. A review of the literature, however, has revealed a morbidity and mortality rate of 11% to 40% in reported series. During the years 1991 through 1993, six patients were identified in whom negative-pressure pulmonary edema developed after various otolaryngologic procedures. Five (84%) of the six patients had complete resolution of the pulmonary edema within 24 hours, and the sixth patient progressed to prolonged mechanical ventilation and eventual death. In an effort to further understand the pathophysiology of this disease, a cardiac evaluation was performed by use of echocardiography on all six patients. In three of the six patients, studies revealed an underlying cardiac anomaly not previously identified by history or physical examination. Findings included one case of hypertrophic cardiomyopathy and two cases of pulmonary and tricuspid valvular insufficiency. This 50% incidence of cardiac anomalies is striking, in contrast to the less than 1% incidence of these anomalies in the general adult population. To our knowledge, this is the first study to implicate an underlying cardiac cause for the generation of negative-pressure pulmonary edema. On the basis of this study, we recommend that echocardiography be a part of the routine evaluation of all patients who manifest negative-pressure pulmonary edema.

Objective assessment of the breathe-right device during exercise in adult males.

In order to improve nasal breathing during competition, many athletes recently have been wearing a spring-loaded, external nasal dilator referred to as the Breathe-Right device (BRD). Although there are many subjective claims that this device improves breathing during exercise, there are currently no controlled studies documenting its efficacy. To determine objectively whether the device improves the nasal airway, 20 subjects (10 Caucasian and 10 African-American) were studied during rest and after 15 minutes of exercise using anterior rhinomanometry and acoustic rhinometry to measure changes in airway resistance and minimal cross-sectional area, respectively. We found that the BRD exerts its main effect in the region of the nasal valve improving the airway an overall 21% in our group of subjects. This anatomic improvement in nasal airway resulted in an overall 27% reduction in nasal resistance in the Caucasian group. However, in the African-American group, a wider range of resistance changes was observed with application of the BRD with significant improvement in nasal resistance in some subjects but paradoxical worsening in others. In the African-American group as a whole, no significant change in nasal resistance occured with application of the BRD. These measured differences are likely due to variations in nasal anatomy that exist not only between races but also between individuals within a given race. In addition, this study confirms the well known decongestant effects of exercise providing anatomic data with acoustic rhinometry not previously documented in the literature. Overall improvement in nasal airway seen with application of the BRD occured independent of these exercise-related decongestant effects.

Adjuvant chemoradiotherapy for locoregionally advanced and high-risk salivary gland malignancies

BackgroundTo report the outcomes of patients with locoregionally advanced and high- risk salivary gland malignancies treated with surgery followed by adjuvant chemoradiotherapy.MethodsFrom 09/1991 - 06/2007, 24 high-risk salivary gland cancer patients were treated with surgery, followed by adjuvant chemoradiotherapy for high-risk pathologic features including, perineural involvement, nodal involvement, positive margins, or T3/T4 tumors. Chemoradiotherapy was delivered for 4-6 alternating week cycles: the most common regimen, TFHX, consisted of 5 days paclitaxel (100 mg/m2 on d1), infusional 5-fluorouracil (600 mg/m2/d × 5d), hydroxyurea (500 mg PO BID), and 1.5 Gy twice daily irradiation followed by a 9-day break without treatment.ResultsMedian follow-up was 42 months. The parotid gland was more frequently involved (n = 17) than minor (n = 4) or submandibular (n = 3) glands. The median radiation dose was 65 Gy (range 55-68 Gy). Acute treatment related toxicity included 46% grade 3 mucositis and 33% grade 3 hematologic toxicity. Six patients required feeding tubes during treatment. One patient progressed locally, 8 patients progressed distantly, and none progressed regionally. Five-year locoregional progression free survival was 96%. The 3 and 5 year overall survival was 79% and 59%, respectively. Long-term complications included persistent xerostomia (n = 5), esophageal stricture requiring dilatation (n = 1), and tempromandibular joint syndrome (n = 1).ConclusionsSurgical resection followed by adjuvant chemoradiotherapy results in promising locoregional control for high-risk salivary malignancy patients.

Well‐differentiated thyroid carcinomas: p53 mutation status and microvessel density

Risk‐stratification schemes exist for well‐differentiated thyroid carcinoma and include prognostic factors such as age, sex, extent of tumor, size of tumor, and presence of metastasis. Controversy continues, however, over the aggressiveness of initial surgical intervention because of anecdotal experiences of poor clinical outcomes in low‐risk patients. Our objective is to determine the prognostic significance of two biologic tumor markers, the p53 gene mutation and CD34 microvessel density (MVD) count, in well‐differentiated tumors of thyroid gland.