Smart (simultaneous modulated accelerated radiation therapy) boost: a new accelerated fractionation schedule for the treatment of head and neck cancer with intensity modulated radiotherapy.

PURPOSE: To report the initial experience in the definitive treatment of head and neck carcinomas using SMART (Simultaneous Modulated Accelerated Radiation Therapy) boost technique. Radiation was delivered via IMRT (Intensity Modulated Radiotherapy). The following parameters were evaluated: acute toxicity, initial tumor response, clinical feasibility, dosimetry and cost. METHODS AND MATERIALS: Between January 1996 and December 1997, 20 patients with primary head and neck carcinomas were treated with SMART boost technique. The treatment fields encompassed two simultaneous targets. The primary target included palpable and visible disease sites. The secondary target included regions at risk for microscopic disease. Daily fractions of 2.4 Gy and 2 Gy were prescribed and delivered to the primary and secondary targets to a total dose of 60 Gy and 50 Gy, respectively. Lower neck nodes were treated with a single conventional anterior portal. This fractionation schedule was completed in 5 weeks with 5 daily fractions weekly. Toxicity was evaluated by RTOG acute toxicity grading criteria, evidence of infection at immobilization screw sites, subjective salivary function, weight loss, and the need for treatment split. Mean follow-up was 15.2 months. Initial tumor response was assessed by clinical and radiographical examinations. Clinical feasibility was evaluated by the criteria: time to treat patient, immobilization, and treatment planning and QA time. In dosimetry, we evaluated the mean doses of both targets and normal tissues and percent targets' volume below goal. To evaluate cost, Medicare allowable charge for SMART boost was compared to those of conventional fractionated and accelerated radiotherapy. RESULTS: ACUTE TOXICITY: None of the patients had a screw site infection and all patients healed well after completion of radiotherapy. Sixteen of 20 patients (80%) completed the treatment within 40 days without any split. Sixteen patients (80%) had RTOG Grade 3 mucositis while 10 patients (50%) had Grade 3 pharyngitis. Three of 20 patients (15%) had weight loss greater than 10% of their pretreatment weight. Ten patients (50%) required intravenous fluids, tube feeding or both. Nine patients (45%) reported moderate xerostomia with significant relief reported within 6 months. INITIAL TUMOR RESPONSE: 19 patients (95 %) had complete response (CR) while one had partial response (PR). The patient with PR had stable disease on imaging at 12 months follow-up. Two patients were found to have lung metastases at 2 months and 5 months follow-up. To date, there have been two local recurrences in the complete responders. Both patients had nasopharyngeal primary; one was retreated with radioactive Cesium-137 implant and the other died from the disease. CLINICAL FEASIBILITY: The average treatment time for a three-arc treatment was 17.5 minutes and 2.5 minutes for each additional arc. Eleven patients (55%) had four-arc treatment while six patients (30%) had five-arc treatment and three patients (15%) had three-arc treatment. Immobilization was reproducible within less than 2 mm. The treatment planning, QA and documentation prior to treatment averaged 2 days. DOSIMETRY: The mean doses to the primary and secondary targets were 64.4 Gy and 54.4 Gy, respectively; 8.9% of the primary target volume and 11.6% of the secondary target volume were below prescribed dose goal. The mean dose delivered to the mandible was 30 Gy, spinal cord 17 Gy, ipsilateral parotid 23 Gy, and contralateral parotid 21 Gy. COST: Total Medicare allowable charge for SMART boost was $7000 compared to $8600 (conventional) and $9400 (accelerated fractionation). CONCLUSIONS: SMART boost technique is an accelerated radiotherapy scheme that can be delivered with acceptable toxicity. It allows parotid sparing as evidenced both clinically and by dosimetry. Initial tumor response has been encouraging. It is clinically feasible and cost saving. A larger population of patients and a long-term fol

Oncocytic mucoepidermoid carcinoma of the salivary glands.

Two parotid mucoepidermoid carcinomas with predominant oncocytic features were initially assessed on frozen section. Because of extensive oncocytic change, it was inferred that the lesions were most likely benign. Permanent sections revealed low-grade mucoepidermoid carcinoma with prominent oncocytic change (in more than 75% of the neoplasms) in both cases. Review of 48 additional consecutive cases of mucoepidermoid carcinoma of the salivary glands revealed prominent oncocytic change (accounting for 60% of the neoplasm) in one high-grade lesion. Phosphotungstic acid-hematoxylin stains revealed strong granular cytoplasmic staining in the oncocytic elements; immunohistochemical stains for antimitochondrial antibodies also showed intense immunoreactivity in these cells. Oncocytic change is not typically a prominent feature of mucoepidermoid carcinoma of the salivary glands, and to our knowledge, only three such cases have been reported previously. Because most salivary gland lesions with oncocytic change are benign, it is important to distinguish mucoepidermoid carcinoma from other entities that may show prominent oncocytic change. We report three additional examples of this rare lesion, two low-grade tumors and one high-grade tumor, and review our experience with oncocytic change in mucoepidermoid carcinoma of the salivary glands.

Neurotropic melanoma of the head and neck.

Neurotropic melanoma is a lesion which simulates a cutaneous fibrous tumor whose clinical course is characterized by local infiltration, multiple recurrences, and commonly by metastasis. Like adenoid-cystic tumors of the head and neck, the neurotropic melanoma has a predilection for perineural invasion and extension along peripheral nerves. Its microscopic picture is characterized by atypical "neuroma-like" patterns of Schwann cells and spindle cells, by poorly defined margins, and by neurotropism. Lentigo malignant melanoma (LMM) is a precursory lesion. The neurotropic melanoma is of particular interest to the head and neck surgeon because in the less than 50 reported cases of this rare tumor the preponderant sites were head, neck, and lip. We report two cases of neurotropic melanoma of the head and neck which demonstrate the characteristic perineural invasion of cranial nerves and extension along cranial nerves to the central nervous system. The clinical and pathologic features of the neurotropic melanoma are reviewed and the key diagnostic and therapeutic considerations in these patients are discussed.

Capsular significance in parotid tumor surgery: reality and myths of lateral lobectomy.

Historically, parotid gland surgery has evolved from an operation of surgical enucleation to that of lateral lobectomy or total parotidectomy with facial nerve dissection. While the enucleation operation originally resulted in recurrence rates as high as 45% in some series, the technique of lateral lobectomy has resulted in recurrence rates of 2% in benign tumors. However, the currently recommended procedure of lateral lobectomy or total parotidectomy with facial nerve preservation for benign or low grade malignant tumors is not a pure en bloc resection in most cases, and in fact enucleation in part or total is often the reality of the operation. Tumor characterization, technical features, and operative findings of parotid gland surgery are examined in 100 consecutive cases. In over 60% of the cases, superficial or total parotidectomy with facial nerve preservation incorporated the principle of limited enucleation or capsular dissection at some point in the technique. The illusion that en bloc removal of parotid tumors with wide surgical margins is discredited. The reality of the procedure and the reasons for its success are examined.

Neuroendocrine neoplasms of the larynx.

Neuroendocrine neoplasms of the larynx are a rare group of tumors that include carcinoid tumor, atypical carcinoid tumor, and small cell carcinoma. These neoplasms pose interesting diagnostic, prognostic, and therapeutic dilemmas, and they are, as a whole, aggressive tumors with a tendency for local and distant spread. The authors of this study examined six new cases of laryngeal neuroendocrine neoplasms. One case manifested itself as a primary atypical carcinoid tumor and caused a "carcinoid syndrome." The remaining five cases were small cell carcinomas of the larynx. Histologic, immunocytochemical, DNA flow cytometric, and p53 studies were performed on all cases. The expression of neuron-specific enolase and chromogranin were the most useful markers in this group of tumors. Overexpression of p53 protein was present in the majority of cases, including the atypical carcinoid tumor. The implications of these studies for diagnosis, classification, and treatment are discussed.

Isotretinoin therapy for recurrent respiratory papillomatosis.

Retinoic acid has been advocated for use in several premalignant and malignant epithelial lesions of the head and neck, including benign recurrent respiratory papillomatosis, with varying results. We describe a 24-year-old man with extensive tracheoesophageal and bronchoalveolar papillomatosis that degenerated into squamous cell carcinoma. Multiple endoscopic carbon dioxide laser excisions, at one point performed on a weekly basis, as well as a prolonged trial of interferon, failed to control the progression of his disease. Isotretinoin (13-cis-retinoic acid) therapy (1 mg/kg per day) was instituted, with dramatic clinical, radiographic, and functional improvement. The patient experienced no significant toxic effects and required no endoscopic procedures over a 6-month period. We propose that isotretinoin may be an effective adjuvant therapy for aggressive respiratory papillomatosis.

Prevalence of human papillomavirus in inverted nasal papillomas.

Human papillomaviruses (HPVs) have been associated with both benign and malignant neoplasms of the head and neck. To determine the prevalence and types of HPVs in this neoplasm, we examined fixed tissue from 21 patients by in situ hybridization. Human papillomavirus types 6b and 11 probes were used, and hybridization was positive to both types in lesions from 16 (76%) of 21 patients. Hybridization to the HPV-11 probe resulted in the most intense nuclear staining throughout the epithelium, probably indicating a high copy number. The high incidence of viral DNA sequences found in this tumor suggests a potential etiologic role. Therapeutic implications are briefly discussed.

A new technique for total reconstruction of the lower lip in a patient with malignant melanoma.

A very rare case of malignant melanoma of the lower lip was presented. While there are many concepts and techniques for reconstruction of the lower lip including advancement flaps, switching flaps, rotation flaps, and regional flaps from the cheek, upper lip, tongue, forehead, neck, and chest, no single flap is ideal in every instance. Lower lip reconstruction utilizing a modification of bilateral nasolabial flaps has been described. The distinct advantages of utilizing myocutaneous flaps in a Z augmentation manner, including the maintenance of good functional competence of the lower lip, maintenance of adequate oral commissure diameter, and a good cosmetic result, have been demonstrated. While no single technique for reconstruction of the lower lip is ideal for every case, we feel that the method presented here offers a very good option when faced with the challenge of complete reconstruction of the lower lip.

Does the severity of sinus computed tomography findings predict outcome in chronic sinusitis?

OBJECTIVES: We studied the association between the severity of pretreatment CT scan findings and the improvement in symptoms of chronic sinusitis after treatment. METHODS: We analyzed data from an ongoing prospective, nonrandomized clinical outcomes study of patients treated for chronic sinusitis at a tertiary-care academic medical center (n = 57, mean age 46.8 years). Disease-specific symptom severity was measured with a validated health status instrument, and CT stage was quantified with the Harvard CT staging system. RESULTS: In a multivariate analysis, symptom severity based on CT findings emerged as a strong predictor of both improvement in symptom score outcome (beta = 0.47, P = 0.01) and absolute symptom level after treatment (beta = -0.58, P = 0.001). CONCLUSIONS: Severity as assessed by a pretreatment CT scan is a strong predictor of outcome. Patients with higher symptom severity based on CT scans showed significantly larger improvement and lower absolute levels of symptom severity after treatment. This study links CT scan findings and subjective patient-based outcomes (symptom scores) using a validated outcomes instrument.

Adenoid cystic carcinoma of the subglottic region.

Adenoid cystic carcinoma is one of the most common malignancies of the minor salivary glands in the head and neck. However, adenoid cystic carcinoma of the larynx is very rare, with less than 75 cases reported in the literature. We present three cases of adenoid cystic carcinoma of the subglottic region with 6-year, 9-year, and 18-year follow-up, respectively. The literature on adenoid cystic carcinoma of the subglottic area is reviewed. Symptoms of long duration, slow progressive growth with tendency for local recurrence, and eventual development of pulmonary metastasis is common. Five-year survival statistics do not appear as relevant as 10- and 20-year survival rates in this entity because of the often slow but pernicious nature of adenoid cystic carcinoma of the subglottic area. Despite aggressive therapy, the disease often leads to the eventual death of the patient. In our series one patient died, and two patients are alive and free of disease. The evaluation, treatment, and clinical course of this disease is discussed.

Further observations on the treatment of recurrent respiratory papillomatosis with interferon: a comparison of sources.

Between June 1982 and March 1983, 11 patients with aggressive recurrent respiratory papillomatosis were treated with alpha or human leukocyte interferon (IFN) that was produced by and purchased from the New York Blood Center, Inc. The year before, nine of these patients had been on a similar protocol utilizing alpha-IFN that had been supplied by the Finnish Red Cross Blood Transfusion Service. Comparisons regarding response and toxicity were made and are reported. In our series we have not seen an overall difference in response of papillomatosis to these two IFNs. As many of our patients responded better to the New York product as responded worse. There is a suggestion, however, that the New York product is associated with less toxicity than the Finnish IFN.

Life-threatening presentations of fibrovascular esophageal and hypopharyngeal polyps.

Giant fibrovascular polyps of the esophagus and hypopharynx are benign tumors of the upper digestive tract. Although a rare cause of asphyxiation, laryngeal impaction by a regurgitated polyp of the esophagus may be the initial symptom that brings the patient to request medical attention. Two new cases of giant fibrovascular polyps with dramatic and potentially life-threatening presentations illustrate the unpredictable behavior of these unusual tumors. Both patients presented to the emergency center with a history of coughing and eructation followed by temporary airway obstruction that was relieved by clenching a regurgitated fleshy mass between the teeth. Diagnostic and therapeutic intervention requires aggressive airway management, radiographic and endoscopic evaluation, and definitive surgical treatment. Tracheotomy was required in one patient, and successful endotracheal intubation provided satisfactory airway control in the second. Esophagoscopy revealed the origin of both tumors to be near the cricopharyngeal muscle. Complete surgical excision was curative in both cases.

The use of intensity modulated radiotherapy for the treatment of extensive and recurrent juvenile angiofibroma.

These case series are presented to describe the application and advantages of intensity modulated radiotherapy (IMRT) for the treatment of extensive and/or recurrent juvenile angiofibroma. Two patients were diagnosed with recurrence at 11 and 13 months postoperatively, and one was surgically unresectable. The affected areas included the base of skull, cavernous sinus, pterygopalatine fossa, infratemporal fossa, posterior orbit and nasopharynx. Highly conformal IMRT was delivered with limited radiation doses to the optic nerves, optic chiasm, brainstem, brain, spinal cord, lens, retina, mandible, and parotid. The total dose delivered to the tumor varied from 3400 to 4500 cGy. The tumor shrunk radiographically in all three cases and there was no endoscopic evidence of disease in two cases at 15 months and 40 months. There was no acute toxicity. Late toxicity was limited to one episode of epistaxis and persistent rhinitis in one patient. In conclusion, IMRT provides several advantages over conventional radiotherapy in the treatment of recurrent juvenile angiofibroma.

Intensity-modulated radiotherapy: first results with this new technology on neoplasms of the head and neck.

Intensity-modulated beam radiotherapy (IMRT) delivers a highly conformal, three-dimensional (3-D) distribution of radiation doses that is not possible with conventional methods. When administered to patients with head and neck tumors, IMRT allows for the treatment of multiple targets with different doses, while simultaneously minimizing radiation to uninvolved critical structures such as the parotid glands, optic chiasm, and mandible. With 3-D computerized dose optimization, IMRT is a vast improvement over the customary trial-and-error method of treatment planning. We retrospectively reviewed the charts of the first 28 head and neck patients at our institution who were treated with IMRT. All had head and neck neoplasms, including squamous cell carcinoma, adenoid cystic carcinoma, paraganglioma, and angiofibroma. Total radiation doses ranged from 1,400 to 7,100 cGy, and daily doses ranged from 150 to 400 cGy/day. A quality assurance system ensured that computer-generated dosimetry matched film dosimetry in all cases. For midline tumors, this system allowed us to decrease the dose to the parotid glands to less than 3,000 cGy. The incidence of acute toxicity was drastically lower than that seen with conventional radiotherapy delivery to similar sites. This is the first report of the application of IMRT strictly to head and neck neoplasms. We discuss the indications, technique, and initial results of this promising new technology. We also introduce the concept of the Simultaneous Modulated Accelerated Radiation Therapy boost technique, which has several advantages over other altered fractionation schemes.