Nicholas J. Cassisi

Squamous Cell Carcinoma of the Oropharynx Surgery, Radiation Therapy, or Both

The treatment of patients with squamous cell carcinoma (SCC) of the oropharynx remains controversial. No randomized trial has addressed adequately the question of whether surgery (S), radiation therapy (RT), or combined treatment is most effective.

Postoperative irradiation for squamous cell carcinoma of the head and neck: an analysis of treatment results and complications☆

One hundred thirty-four patients with advanced head and neck cancer were treated with radical surgery and postoperative radiation therapy between October 1964 and October 1984. All patients had greater than or equal to 2 years and 84% had greater than or equal to 5 years of follow-up. All patients included in the study were scheduled to receive continuous-course irradiation following a major cancer operation for previously untreated squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx and began radiation treatment less than or equal to 3 months after the surgical procedure. Ninety-six percent had AJCC pathologic Stage III or IV cancer, and all were without evidence of gross disease at the start of irradiation. The majority of recurrences above the clavicles occurred in the primary field (84%) as opposed to the posterior strip (8%) or low neck (8%). Based on multivariate analysis and tabular comparisons, 4 factors were found to be significantly important for predicting disease control above the clavicles: (a) Surgical margin (5-year actuarial control with invasive cancer at the margin, 53%, versus 81% with negative margins, p = .009). Patients with close margins or in situ cancer at the margins had the same rate of control as those with negative margins. (b) Primary site (oral cavity, 64%, versus other sites, 83%; p = .029). (c) Neck Stage (N0-1 versus N2-3). (d) Number of indications for irradiation--for example, bone invasion, multiple positive nodes, perineural invasion (1-3 indications, 85%, versus greater than or equal to 4, 62%; p = .06). The rate of disease control above the clavicles did not correlate well with AJCC pathologic stage: Stage I-II, 67%; Stage III, 81%; Stage IVA (T1-3, N2-3A), 68%; Stage IVB (T4 and/or N3B), 80%. The interval between surgery and the start of irradiation (range 1-10 weeks) also was not prognostically important, even with stratification by tumor dose, surgical margin, and number of indications for irradiation. At 5 years, the actuarial survival rate was 33% for the entire group; for patients with invasive cancer at the margin, the survival rate was approximately half that of those whose margins were free of invasive cancer (17% versus 37%). Based on multivariate analysis, 2 factors were found to significantly increase the probability of death due to cancer: (a) neck Stage (N0-1 versus N2-3); (b) extension of tumor from the primary site into the skin or soft tissues of the neck.(ABSTRACT TRUNCATED AT 400 WORDS)

Squamous cell carcinoma of the head and neck treated with radiation therapy the role of neck dissection for clinically positive neck nodes

This is an analysis of 161 patients with squamous cell carcinoma of the head and neck treated with irradiation to the primary site and neck followed by a neck dissection(s) for clinically positive neck nodes. Patients were treated between October 1964 and December 1982; there was a minimum 2-year follow-up. Fifty-two patients were deleted from analysis of neck disease control because they died of intercurrent disease or cancer less than 2 years from treatment with the neck continuously disease-free. All patients are included in the analysis of complications. Neck disease control rate was the same for radiation plus neck dissection or radiation therapy alone for solitary nodes less than 3 cm. As the size and number of nodes increased, there was a higher rate of neck disease control for combined treatment as compared with irradiation alone. The neck disease control rate, size for size, was lower for patients with fixed nodes and for those with residual tumor in the pathologic specimen. There was no difference in neck disease control as a function of the interval between irradiation and neck dissection. For nodes less than or equal to 6 cm, a minimum node dose of 5000 rad appeared to be sufficient for control, whereas for nodes greater than 6 cm, at least 6000 rad appeared to be required for optimal control. Fixed nodes required a higher dose compared to mobile masses. The incidence of postoperative complications was increased with maximum subcutaneous doses of greater than or equal to 6000 rad. There was also an increased incidence of postoperative complications for patients undergoing simultaneous, as compared with staged, bilateral neck dissection.

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

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.

Hyperfractionation for head and neck cancer

Between March 1978 and April 1984, 144 patients with 148 moderately advanced to advanced primary squamous cell carcinomas of the head and neck received treatment with curative intent with twice-a-day irradiation (120 cGy/fraction, 4-6 hour interfraction interval). Eighty-eight percent of the patients had AJCC Stage III-IV cancers. One hundred and thirty-two patients received irradiation alone to the primary site with or without radical neck dissection, with surgery reserved for salvage. The total doses administered were 7440-7920 cGy in the majority of instances. In 19 patients with oropharyngeal lesions, a 1000-1500 cGy radium needle boost was added after the basic dose. Twelve patients received preoperative irradiation (5040-6000 cGy) followed by primary resection and radical neck dissection. Local control results following irradiation alone to total doses of greater than 7000 cGy with minimum 2-year follow-up were 25/31 (81%), 38/50 (76%), and 5/25 (20%) for T2, T3, and T4 cancers, respectively. Local control rates did not correlate well with total dose. Local control following preoperative irradiation plus primary resection was obtained in 4 of 5 T3 and 2 of 3 T4 primary lesions. The 5-year actuarial rates of neck control were 100% for N0 (45 patients), 90% for N1 (25 patients), 77% for N2 (23 patients), 50% for N3A (9 patients), and 70% for N3B (42 patients). The 5-year actuarial rates of continuous disease control above the clavicles were 73% for Stage III, 64% for Stage IVA, and 32% for Stage IVB. The actuarial 4-year rate of continuous disease control above the clavicles was 78% for Stage II. For patients whose disease was controlled above the clavicles, distant metastases developed in 4% of patients with Stage II-III disease and in 18% of patients with Stage IV disease. Radiation complications following irradiation alone to the primary site correlated with total dose. Complications of planned neck dissection(s) were acceptable. Complications of salvage surgery at the primary site were similar to those seen in patients treated once a day. The actuarial 5-year survival rates, according to modified AJCC stage, were 59% for Stage III, 37% for Stage IVA, and 23% for Stage IVB. The actuarial 4-year survival rate for Stage II was 69%. Compared to historical control groups treated with once-a-day, continuous-course irradiation at our institution, twice-a-day treatment has produced local control results that are higher by 10-15 percentage points.

Malignant tumors of the nasal cavity and ethmoid and sphenoid sinuses

Between October 1964 and December 1983, 48 patients with malignant tumors of the nasal cavity (31), ethmoid sinus (13), or sphenoid sinus (4) were treated with curative intent by radiation therapy. There were 21 squamous cell carcinomas, 14 minor salivary gland tumors (adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma), 3 malignant melanomas, 2 soft tissue sarcomas, and 8 esthesioneuroblastomas. Forty-two patients were treated with irradiation alone and six with planned combined irradiation and surgery. The 10-year actuarial local control rate for Stage I (limited to site of origin; 7 patients) was 100%; for Stage II (extension to adjacent sites, e.g., adjacent sinuses, orbit, pterygomaxillary fossa, nasopharynx; 19 patients) was 53%; and for Stage III (destruction of skull base or pterygoid plates, or intracranial extension; 22 patients) was 30%. Of 24 failures at the primary site, 10 occurred greater than 24 months after completion of irradiation. With the exception of adenoid cystic carcinoma (17% local control at 15 years), the ultimate local control rates for all histologies were in the range of 40% to 60%. Of 7 patients with documented intracranial extension, 3 (43%) remained free from local recurrence 3.5, 4, and 9 years after treatment. The 5-, 10-, 15-, and 20-year uncorrected actuarial survival rates for all 48 patients were 52%, 30%, 22%, and 22%, respectively. Continuous disease-free survival according to stage at 10 years was 86% for Stage I, 42% for Stage II, and 22% for Stage III. The single failure in a patient with Stage I disease was a lymph node metastasis that was successfully managed by radical neck dissection. The orbit was grossly invaded by tumor prior to treatment in 22 patients (46%). Sixteen (33%) of 48 patients developed unilateral blindness secondary to radiation retinopathy or optic neuropathy; in the majority of these patients the complication was anticipated because the ipsilateral eye was irradiated to a high dose. Four patients (8%) unexpectedly developed bilateral blindness 17, 35, 46, and 90 months following treatment owing to optic nerve injury. A discussion of possible means of avoiding this latter, unacceptable complication is included.

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.

Oropharyngeal carcinoma treated with radiotherapy: A 30-year experience

PURPOSE This study was done to determine the outcome in patients with oropharyngeal carcinoma treated at the University of Florida with radiotherapy alone to the primary site, for comparison with reported results of other types of treatment. METHODS AND MATERIALS Of a consecutive cohort of 785 patients with biopsy-proven, previously untreated, invasive squamous cell carcinoma of the oropharynx, this report is based on the 490 patients who had continuous-course irradiation with curative intent at the University of Florida between October 1964 and January 1991. All patients had a minimum 2-year follow-up. Forty-eight percent had Stage T3 or T4 disease, and 64% had clinically apparent neck node metastases. The median radiation dose was 68 Gy for once-a-day treatment and 76.8 Gy for twice-a-day treatment. Patients with advanced neck node disease had planned neck dissection(s) after radiotherapy. RESULTS The overall local control rate after radiotherapy alone was 73%. The ultimate local control rate (including surgical salvage) was 78%. At 5 years, the probability of control of neck disease was 85%; control above the clavicles, 67%; absolute survival, 44%; cause-specific survival, 77%; distant metastasis (as the first or only site of failure), 11%. Thirteen patients (2.6%) experienced severe treatment complications. CONCLUSION Radiotherapy results in tumor control and survival rates comparable with rates achieved with combined irradiation and surgery, with less morbidity.

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.