Treatment of paragangliomas with radiation therapy.

Paragangliomas of the head and neck may be treated successfully with surgery, radiation therapy, or stereotactic radiosurgery. The choice of treatment depends on the location and extent of the tumor, the presence of multiple tumors, the age and health of the patient, and the preference of the patient and attending physician. This article reviews the role of radiation therapy in the treatment of patients with paragangliomas of the head and neck.

Squamous cell carcinoma metastatic to the neck from an unknown head and neck primary site.

Squamous cell carcinoma metastatic to the neck from an unknown head and neck primary site is relatively uncommon and presents a challenging diagnostic and therapeutic dilemma. Diagnostic evaluation includes fine-needle aspiration of the neck mass, chest roentgenography, computed tomography, and/or magnetic resonance imaging of the head and neck, followed by panendoscopy and biopsies. The primary tumor will be detected in approximately 40% of patients; approximately 80% of cancers are located in the base of the tongue or tonsillar fossa. Management options include treatment of the neck alone or both sides of the neck and the potential head and neck primary sites. The latter approach is associated with better long-term control above the clavicles. The 5-year survival rate is approximately 50% after treatment and is influenced by the extent of neck disease. In this article, we review the pertinent literature.

Long-term results of radiation therapy for juvenile nasopharyngeal angiofibroma.

PURPOSE: To analyze 15 patients treated with radiation therapy for juvenile nasopharyngeal angiofibroma (JNA) between June 1975 and March 1996. MATERIALS AND METHODS: All patients had a 2.5-year minimum follow-up. All patients had advanced disease (Chandler stage III or stage IV); two thirds of the patients had intracranial extension. RESULTS: Local control after radiotherapy was obtained in 13 of 15 patients (85%). Two patients had local recurrences, and both were salvaged with surgery for an ultimate local control rate of 100%. Late complications included cataracts in 3 patients, delayed transient central nervous system (CNS) syndrome in 1 patient, and a basal cell carcinoma of the skin in 1 patient. Of 15 patients, 13 (85%) had a complete response (CR) on physical examination following radiation therapy. The median time to CR was 13 months (range, 1 to 39 months). Of 6 patients with residual disease in more than 24 months, 2 (33%) had a recurrence, whereas no patient achieving CR in less than 24 months experienced a recurrence. CONCLUSIONS: Radiotherapy is an effective treatment for advanced JNA. Tumor regression usually occurs slowly over several months. JNAs that are slow to regress (greater than 2 years) may have an increased risk of recurrence.

Definitive radiotherapy in the management of chemodectomas arising in the temporal bone, carotid body, and glomus vagale.

PURPOSE: To evaluate the results of treatment for 71 patients with 80 chemodectomas of the temporal bone, carotid body, or glomus vagale who were treated with radiation therapy (RT) alone (72 tumors in 71 patients) or subtotal resection and RT (8 tumors) at the University of Florida between 1968 and 1998. METHODS AND MATERIALS: Sixty-six lesions were previously untreated, whereas 14 had undergone prior treatment (surgery, 11 lesions; RT, 1 lesion; or both, 2 lesions) and were treated for locally recurrent disease. All three patients who received prior RT had been treated at other institutions. Patients had minimum follow-up times as follows: 2 years, 66 patients (93%); 5 years, 53 patients (75%); 10 years, 37 patients (52%); 15 years, 29 patients (41%); 20 years, 18 patients (25%); 25 years, 12 patients (17%); and 30 years, 4 patients (6%). RESULTS: There were five local recurrences at 2.6 years, 4.6 years, 5.3 years, 8.3 years, and 18.8 years, respectively. Four were in glomus jugulare tumors and one was a carotid body tumor. Two of the four patients with glomus jugulare failures were salvaged, one with stereotactic radiosurgery and one with surgery and postoperative RT at another institution. Two of the five recurrences had been treated previously at other institutions with RT and/or surgery. Treatment for a third recurrence was discontinued, against medical advice, before receiving the prescribed dose. There were, therefore, only 2 failures in 65 previously untreated lesions receiving the prescribed course of RT. The overall crude local control rate for all 80 lesions was 94%, with an ultimate local control rate of 96% after salvage treatment. The incidence of treatment-related complications was low. CONCLUSIONS: Irradiation offers a high probability of tumor control with relatively minimal risks for patients with chemodectomas of the temporal bone and neck. There were no severe treatment complications.

Organ preservation with radiotherapy for T1-T2 carcinoma of the pyriform sinus.

PURPOSE: To report long-term results using radiotherapy with or without a planned neck dissection for T1-T2 carcinoma of the pyriform sinus. METHODS: An analysis of 101 patients treated at the University of Florida with RT with or without a planned neck dissection for organ preservation. RESULTS: The 5-year local control rates after RT were 90% for T1 cancers and 80% for T2 lesions. The only parameter that significantly influenced local control in univariate analyses was apex involvement for T1 tumors. Multivariate analysis revealed no parameter that significantly affected local control. Cause-specific survival rates at 5 years were as follows: stage I-II, 96%; stage III, 62%; stage IVA, 49%; and stage IVB, 33%. The absolute survival rates were as follows: stage I, 57%; stage II, 61%; stage III, 41%; stage IVA, 29%; and stage IVB, 25%. Moderate to severe long-term complications developed in 12% of patients. CONCLUSIONS: RT alone or combined with a planned neck dissection resulted in local control with larynx preservation in a high proportion of patients. The chance of cure is comparable to that observed after conservation surgery, and the risk of major complications is lower. The addition of adjuvant chemotherapy is unlikely to improve the probability of organ preservation, but might improve locoregional control for patients with advanced nodal disease.

Radiation therapy in inverted papillomas of the nasal cavity and paranasal sinuses.

PURPOSE: Between December 1969 and September 1989, a total of 10 patients with advanced and/or recurrent inverted or cylindrical cell papillomas were treated with irradiation at the University of Florida in Gainesville. MATERIALS AND METHODS: Nine of 10 patients had 1 or more recurrences before they received radiation therapy. Three patients were treated with irradiation alone, and 7 patients received surgery and irradiation (preoperatively in 1 patient and postoperatively in 6 patients). Eight patients had inverted papillomas (3 with concomitant squamous cell carcinoma), and 2 patients had cylindrical cell papillomas. RESULTS: Local recurrence developed in 4 patients at 1.5, 6.5, 12, and 13 years after treatment. No evidence of recurrence was observed in 6 patients at 7, 8.5, 8.5, 9, 9, and 20.5 years after treatment. Four patients died of intercurrent disease. No patient developed a malignant transformation. Significant complications of treatment included, in 1 patient, an area of bone exposure in the orbit that necessitated debridement. CONCLUSION: Surgery is the primary treatment of this entity. Radiation therapy should be considered in patients with incompletely resectable lesions, multiply recurrent tumors, and tumors associated with malignancy.

Radiation therapy for squamous cell carcinoma of the tonsillar region: a preferred alternative to surgery?

PURPOSE: There are no definitive randomized studies that compare radiotherapy (RT) with surgery for tonsillar cancer. The purpose of this study was to evaluate the results of RT alone and RT combined with a planned neck dissection for carcinoma of the tonsillar area and to compare these data with the results of treatment with primary surgery. PATIENTS AND METHODS: Four hundred patients were treated between October 1964 and December 1997 and observed for at least 2 years. One hundred forty-one patients underwent planned neck dissection, and 18 patients received induction (17 patients) or concomitant (one patient) chemotherapy. RESULTS: Five-year local control rates, by tumor stage, were as follows: T1, 83%; T2, 81%; T3, 74%; and T4, 60%. Multivariate analysis revealed that local control was significantly influenced by tumor stage (P =.0001), fractionation schedule (P =.0038), and external beam dose (P =.0227). Local control after RT for early-stage cancers was higher for tonsillar fossa/posterior pillar cancers than for those arising from the anterior tonsillar pillar. Five-year cause-specific survival rates, by disease stage, were as follows: I, 100%; II, 86%; III, 82%; IVa, 63%; and IVb, 22%. Multivariate analysis revealed that cause-specific survival was significantly influenced by overall stage (P =.0001), planned neck dissection (P =.0074), and histologic differentiation (P =.0307). The incidence of severe late complications after treatment was 5%. CONCLUSION: RT alone or combined with a planned neck dissection provides cure rates that are as good as those after surgery and is associated with a lower rate of severe complications.

Skin cancer of the head and neck with clinical perineural invasion.

PURPOSE: To review treatment and outcomes in 62 patients with clinical and/or gross evidence of perineural invasion from skin cancer of the head and neck. METHODS AND MATERIALS: Sixty-two patients received radiotherapy at the University of Florida as part or all of their treatment between January 1965 and April 1995. All patients had clinical signs and symptoms of perineural involvement and/or documentation of tumor extending to grossly involve nerve(s). Twenty-one patients underwent therapy for previously untreated lesions, including 12 who received radiotherapy alone and nine who had surgery with postoperative radiotherapy. Forty-one patients underwent therapy for recurrent lesions, including 18 treated with radiotherapy alone and 23 who received preoperative or postoperative radiotherapy. RESULTS: Factors on multivariate analysis that predicted local control included patient age, previously untreated vs. recurrent lesions, presence of clinical symptoms, and extent of radiotherapy fields. Recurrence patterns were predominantly local; 26 of 31 patients (84%) who developed local recurrence after treatment had recurrent cancer limited to the primary site. CONCLUSIONS: Many patients with skin cancer and symptomatic perineural invasion have disease that is incompletely resectable. Approximately half these patients will be cured with aggressive irradiation alone or combined with surgery. Age, prior treatment, and clinical symptoms influence the likelihood of cure.

Is radiation therapy a preferred alternative to surgery for squamous cell carcinoma of the base of tongue?

PURPOSE: To evaluate irradiation alone for treatment of base-of-tongue cancer. PATIENTS AND METHODS: Two hundred seventeen patients with squamous cell carcinoma of the base of tongue were treated with radiation alone and had follow-up for >/= 2 years. RESULTS: Local control rates at 5 years were as follows: T1, 96%; T2, 91%; T3, 81%; and T4, 38%. Multivariate analysis revealed that T stage (P =.0001) and overall treatment time (P =.0006) significantly influenced local control. The 5-year rates of local-regional control were as follows: I, 100%; II, 100%; III, 83%; IVA, 64%; and IVB, 65%. Multivariate analysis revealed that the following parameters significantly affect the probability of this end point: T stage (P =.0001), overall treatment time (P =.0001), overall stage (P =.0131), and addition of a neck dissection (P =.0021). The rates of absolute and cause-specific survival at 5 years were as follows: I, 50% and 100%; II, 81% and 100%; III, 65% and 76%; IVA, 42% and 56%; and IVB, 44% and 52%. Severe radiation complications developed in eight patients (4%). CONCLUSION: The likelihood of cure after external-beam irradiation was related to stage, overall treatment time, and addition of a planned neck dissection. The local-regional control rates and survival rates after radiation therapy were comparable to those after surgery, and the morbidity associated with irradiation was less.

Salvage treatment for neck recurrence after irradiation alone for head and neck squamous cell carcinoma with clinically positive neck nodes.

BACKGROUND: To analyze the likelihood of salvage for patients with recurrence in the neck after radiotherapy. METHOD: Recurrent disease developed in the neck of 51 patients after primary irradiation for head and neck carcinoma. Salvage was defined as no recurrence of cancer anywhere for at least 1 year after initial salvage treatment and continuously thereafter. RESULTS: Thirty-three patients (65%) did not undergo a salvage attempt: 18 had unresectable disease; 9 were medically unfit, 4 had distant metastasis; and 2 refused treatment. Eighteen patients (35%) underwent salvage treatment with chemotherapy alone (4 patients), chemotherapy and neck dissection (1 patient), neck dissection alone (11 patients), or surgery with radiotherapy (2 patients). After the initial salvage treatment, recurrent local-regional and/or distant disease developed in all patients. Recurrence was in the neck alone in 10 patients (55%); neck and distant sites in 3 patients (17%); neck, primary site, and distant sites in 2 patients (11%); and with distant metastasis alone in 3 patients (17%). Control of neck disease at 5 years was 9% for the 18 patients who underwent a salvage attempt, as well as for all 51 patients. For the overall group, absolute and cause-specific survival rates were both 10% at 5 years. CONCLUSIONS: The likelihood of successful salvage treatment after a neck recurrence following radiotherapy is remote.

Squamous cell carcinoma of the nasal vestibule.

BACKGROUND AND METHODS: Sixty patients were treated with radiation therapy alone (56 patients) or followed by surgery (4 patients) between 1970 and 1995 for squamous cell carcinoma of the nasal vestibule. RESULTS: Local control rates at five years after irradiation alone in 56 patients were: T1-T2, 94%; T4, 71%; and overall, 85%. Multivariate analysis revealed that tumor size and bone invasion significantly influenced local control. All four patients with extensive T4 tumors treated with radiation therapy plus surgery were cured. Cause-specific survival rates at five years for 56 patients treated with radiation therapy alone were: T1-T2, 94%; T4, 86%; and overall, 91%. Multivariate analysis revealed that bone invasion and tumor size adversely influenced cause-specific survival. No patient treated with irradiation alone experienced a major complication, compared with three of four patients who underwent irradiation and surgery. CONCLUSIONS: Radiation therapy results in a high cure rate with good cosmesis. Patients with extensive T4 cancers have an improved chance of cure with radiation and surgery but more complications.

Squamous cell carcinoma of the glottic larynx: a review emphasizing the University of Florida philosophy.

BACKGROUND: Squamous cell carcinoma of the glottic larynx is strongly related to cigarette smoking and excessive ethanol intake. It is the most common head and neck cancer other than skin cancer. METHODS: We reviewed pertinent literature relative to etiology, epidemiology, and treatment results, with emphasis on the treatment philosophy at the University of Florida. RESULTS: The goals of treatment are cure and retention of a functional larynx. The probability of achieving both goals is high for patients with early disease. In contrast, a significant proportion of patients with advanced disease may be cured but must have a total laryngectomy as part of the treatment. CONCLUSIONS: Treatment options are influenced by the extent of disease and patient preference. Options include transoral laser resection, open partial laryngectomy, radiation therapy, and total laryngectomy. Adjuvant chemotherapy may have a role in advanced disease.

Diagnostic evaluation of squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site.

BACKGROUND: The purpose of this study was to evaluate the efficacy of the modern diagnostic evaluation for squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site. METHODS: One hundred thirty patients were evaluated between June 1983 and June 1997. All underwent head and neck examinations, head and neck computed tomography (CT), and/or magnetic resonance imaging (MRI) scans, panendoscopies, and biopsies of head and neck mucosal sites. Twenty-four patients underwent 2-[fluorine-18]-2-deoxy-D-glucose (FDG) single photon emission computed tomography (SPECT); 34 patients underwent tonsillectomy. RESULTS: The primary site was identified in 56 patients (43%); the likelihood was increased in patients with suggestive findings on physical examination and/or radiographic evaluation. Eighty-three percent of the lesions were located in the tonsillar fossa and base of tongue. Results of FDG-SPECT scans were positive in 20 patients (83%); the primary tumor was detected in 7 patients (35%). Twelve (35%) of 34 patients who underwent tonsillectomy had a primary tumor discovered in the tonsillar fossa. Multivariate analysis of successful primary site detection revealed that suggestive findings on physical examination (p= .0225) and suggestive findings on CT and/or MRI (p = .0013) were significantly related to this end point. CONCLUSION: The primary lesion will be detected in over 40% of patients with physical examination of the head and neck and CT and/or MRI followed by panendoscopy and biopsies. Limited data pertaining to FDG-SPECT suggest that this provides additional useful information in a small subset of patients. Tonsillectomy is useful for those with suggestive findings on physical examination and/or radiographic evaluation.

Radiotherapy in the management of chemodectomas of the carotid body and glomus vagale.

BACKGROUND: Because only limited data are available pertaining to radiotherapy for chemodectomas of the carotid body and glomus vagale, we reviewed our experience. METHODS: Fifteen patients with 23 chemodectomas of either the carotid body or glomus vagale were treated with radiotherapy at the University of Florida between 1981 and 1995. Eighteen lesions were previously untreated. One patient had received prior radiotherapy at another institution and four patients had received prior surgery. RESULTS: The local control rate at 10 years, calculated by the Kaplan-Meier product-limit method, was 96% for the overall group of 23 lesions and 100% for the subset of 22 lesions without prior radiotherapy. The 10-year cause-specific survival rate was 89% for all 15 patients and 100% for the 14 patients who had received no prior radiotherapy. No patient experienced a significant complication secondary to irradiation. CONCLUSIONS: Irradiation offers a high probability of tumor control with relatively minimal risks for patients with chemodectomas of the carotid body and glomus vagale.

Laryngeal recovery following type I thyroplasty.

OBJECTIVE: To describe the pattern of laryngeal recovery and its relationship to voice improvement following thyroplasty. DESIGN: We used a 5-point scale to rate 5 laryngeal characteristics preoperatively and 1 day, 1 week, 1 month, and 3 months following thyroplasty. SETTING: A university-affiliated health center. PATIENTS: Forty-four patients who underwent thyroplasty to correct incomplete glottal closure. RESULTS: Improved glottal closure and reduced supraglottic activity followed thyroplasty. Although evidence of postoperative irritation (erythema, edema, or hematoma) was present in many patients, it resolved within the first 1 to 4 weeks postoperatively in 22 (73%) of the 30 subjects available for follow-up at 3 months following thyroplasty. CONCLUSIONS: Thyroplasty is an effective procedure in correcting incomplete glottal closure and works to reduce excessive supraglottic activity in some patients. Recovery from postoperative vocal-fold irritation occurs rapidly, typically between the first week to first month, depending on the type and severity of irritation. These findings may help explain variations in postoperative voice improvement.

Carcinoma of the skin metastatic to the parotid area lymph nodes.

BACKGROUND: We performed an analysis of treatment outcome at the University of Florida for 77 patients with previously untreated carcinoma of the skin metastatic to parotid area lymph nodes. METHODS: Seventy-seven patients with 79 parotid node metastases were treated with curative intent between 1966 and 1994. All patients had a minimum 2-year follow-up. Treatment consisted of radiotherapy alone in 18 patients, preoperative radiotherapy in 6 patients (7 parotids), and postoperative radiotherapy in 53 patients (54 parotids). RESULTS: Overall rate of disease control in the parotid area at 5 years was 82%. Parotid area disease control according to treatment group revealed: surgery and postoperative radiotherapy, 43 of 48 (90%); preoperative radiotherapy and surgery, 4 of 5 (80%); and radiotherapy alone, 8 of 15 (53%). Multivariate analysis of parotid disease control revealed the following: treatment method (p = .0037), N stage (p = .0726), cranial nerve involvement (p = .1851), fixation (p = .1820), skin involvement (p = .1771), and sex (p = .5782). Overall 5-year absolute and cause-specific survival rates were 54% and 68%, respectively. The 5-year cause-specific survival rate was 72% after surgery and postoperative radiotherapy and 59% following radiotherapy alone. Multivariate analysis of cause-specific survival revealed the following: skin involvement (p = .0215), cranial nerve involvement (p = .1549), fixation (p = .0347), N stage (p = .4302), sex (p = .6806), and treatment method (p = .9599). CONCLUSIONS: Our current policy is to treat patients with tumor that is initially resectable with surgery followed by radiotherapy, whereas those who have initially unresectable disease undergo preoperative radiotherapy followed by surgical resection if the tumor becomes resectable. If surgery cannot be performed for medical reasons, patients still have better than a 50% chance of being cured with radiotherapy alone.

T4 laryngeal carcinoma: radiotherapy alone with surgery reserved for salvage.

PURPOSE: To review the results of primary radiation therapy for patients with T4 squamous cell carcinoma of the larynx. METHODS AND MATERIALS: Between October 1964 and October 1994, 43 patients with T4 invasive squamous cell carcinoma of the larynx received radiotherapy with curative intent in the University of Florida Department of Radiation Oncology. All patients had a minimum of 2 years follow-up. There were 26 primary cancers of the supraglottic larynx, 11 of the glottic larynx, and 6 of the subglottic larynx. RESULTS: The 5-year actuarial rate of local control was 52%. By direct calculation, local control was achieved in 8 (38%) of 21 supraglottic carcinomas, 8 (89%) of 9 glottic tumors, and 2 of 6 subglottic tumors. Local control of nonbulky lesions was achieved in 67%, and 38% of bulky lesions were locally controlled. Only 3 (17%) of 18 local recurrences were successfully salvaged by subsequent surgery. There were 2 (5%) severe complications of irradiation. CONCLUSION: From our series, as well as a review of the literature, local control by primary irradiation has been achieved in approximately 50% of patients with T4 laryngeal cancer. Selection factors for choosing irradiation have not been well described: the present series contains a small amount of information suggesting that tumor volume may be a reliable predictor of control, but further substantiation is required.

An analysis of factors influencing the outcome of postoperative irradiation for squamous cell carcinoma of the oral cavity.

PURPOSE: To analyze factors influencing outcome in patients who received postoperative irradiation for advanced squamous cell carcinoma of the oral cavity. METHODS AND MATERIALS: Between October 1964 and November 1993, 134 patients with 135 previously untreated primary invasive squamous cell carcinomas of the oral cavity (excluding the lip) were treated postoperatively with continuous courses of external-beam irradiation at the University of Florida. All patients had a minimum follow-up of 2 years (analysis, December 1995). No patient was lost to follow-up. RESULTS: The 10-year actuarial rates of primary site, neck, and local-regional control were 79%, 88%, and 71%, respectively. Recurrence of cancer above the clavicles developed in 35 patients. Ninety-four percent of the recurrences were within the primary field of irradiation (anterior to the plane of the spinal cord); there were 24 recurrences at the primary site and nine in the upper neck alone. There were no failures in the neck area behind the plane of the spinal cord (i.e., the "posterior strip"). Two failures occurred in the low neck below the level of the thyroid notch. In univariate analyses, factors that affected local-regional control included pathologic stage (I-II vs. III-IV, p = 0.04), margin status (invasive cancer at the margin vs. other, p = 0.0007), multifocal tumor (p = 0.05), perineural invasion (p = 0.04), and number of indications for postoperative irradiation (p = 0.05). Extracapsular nodal extension was marginally significant (p = 0.07). In multivariate analysis, positive margins and number of indications remained significant. These factors were used to define relatively favorable (< 4 indications, margins not positive) and unfavorable (> or = 4 indications and/or margins positive for invasive cancer) groups. For both favorable and unfavorable groups, there were nonsignificant trends toward improved local-regional control for patients who began irradiation within 45-50 days, compared with those whose irradiation began later. There were also nonsignificant trends toward improved control for patients treated with shorter overall irradiation treatment courses. An analysis was also performed on the effects of duration of the overall "treatment package" (from the date of surgery until the last day of irradiation). For patients with unfavorable tumors, there was a significantly higher probability of local-regional control for patients whose overall "treatment package" was < or = 100 days (60% vs. 14%, p = 0.04). The 5-year rate of distant metastasis as the sole site of failure was 8% and was predicted by pathologic N stage (N0-N1, 3%; N2-N3, 16%, p = 0.02), as well as the presence (20%) or absence (6%) of extracapsular nodal extension (p = 0.06). The 5-year freedom-from-relapse rate was 63%. The 5-year survival and cause-specific survival rates were 50% and 67%, respectively. Four severe radiation injuries occurred (3%). CONCLUSION: This paper provides data that define relatively favorable and unfavorable groups of patients in the postoperative setting. Patients with four or more indications for irradiation and/or invasive cancer at the surgical margins have a worse outcome than patients who do not have these negative factors; this is true in spite of the fact that the unfavorable group received higher doses of radiation. Attention should be focused on not only the interval between surgery and irradiation, but also time-dose parameters and the overall duration of the treatment "package."