2.1

Patients

The medical records of 16 consecutive patients treated for newly-diagnosed SNUC of the head and neck between November 1999 and May 2009 were analyzed. Immunohistochemical staining, using a wide variety of markers including cytokeratin, vimentin, neuron-specific enolase, chromogranin, synatophysin, and/or S-100 was performed on all specimens to confirm the diagnostic entity. The median age of all patients was 50 years (range, 36–80 years). Fourteen men and two women were included. All patients underwent pre-treatment physical examination with direct nasopharyngolaryngoscopy and basic laboratory work including complete blood count, liver function tests, and electrolytes. Imaging consisted of computed tomography (CT) and magnetic resonance imaging (MRI) of the head and neck. Four patients (25%) underwent positron emission tomography prior to treatment. No patient had evidence of distant metastasis at initial diagnosis. All patients had locally advanced tumors at diagnosis, with 15 patients (94%) presenting as T4, and the remaining other patient having T3 disease, according to the 2009 American Joint Committee on Cancer (AJCC) staging classification. Four patients had clinically positive neck disease (4 level II, 1 level IB), all of whom were treated with non-surgical approaches. The primary sites were: maxillary sinus (7 patients), nasal cavity (5 patients), and ethmoid sinus (4 patients). This study was approved by all relevant Institutional Review Boards prior to the initiation of data collection.

2.2

Treatment

All patients were presented at a multi-disciplinary tumor conference at initial diagnosis for discussion about management. Treatment strategies were as follows: surgery alone (6 patients); surgery with post-operative radiation therapy with concurrent chemotherapy (4 patients); and non-surgical treatment of definitive radiation therapy with concurrent chemotherapy (6 patients). Generalized criteria for operability were established at the discretion of the surgeon. The surgical approach varied depending on tumor site, extent of disease, and physician expertise. In general, an attempt was made to maximize local control with preservation of cosmetic and functional outcome, while considering the medical comorbidities of the patient. Gross total resection with negative pathological margins was obtained in all patients who underwent surgery.

Radiation therapy technique varied depending on the site of disease, the time period of treatment, and the discretion of the radiation oncologist. All patients were treated with megavoltage equipment using photons or mixed photons and electrons. The clinical target volume was designed to cover the primary tumor site as defined by CT and/or MRI, considering physical examination findings, pathological findings, and the potential for microscopic extension. This typically included both halves of the nasal cavity and ipsilateral maxillary sinus extending to the medial wall of the orbit. Median doses were 60 Gy and 70 Gy in the postoperative and definitive settings, respectively, delivered at standard, once-daily fractionation. Seven patients received intensity-modulated radiotherapy. Concurrent chemotherapy regimens included cisplatin alone (4 patients) and cisplatin and etoposide (4 patients), carboplatin and paclitaxel (2 patients).

Treatment of the neck depended on multiple factors. All patients with clinical and/or radiographic evidence of cervical lymphadenopathy were treated with non-surgical therapy consisting of chemoradiotherapy with target volumes that included the ipsilateral neck. Among patients with clinically N0 disease, elective neck dissection was performed in 4 of 10 surgically-treated patients, with none having pathological evidence of disease. The use of elective neck irradiation after definitive surgery was administered at the discretion of the treating radiation oncologist and was performed in all but 1 case. The prophylactic dose to the uninvolved neck was typically 50–60 Gy.

2.3

Follow-up and statistical analysis

Patients were evaluated every 1 to 2 months during the first year after completion of treatment, every 3 months during the subsequent 6–12 months, every 4–6 months until 3 years post-treatment, and annually thereafter. Follow-up consisted of routine physical examination and review of systems, focusing particularly on the head and neck as well as the presence or absence of neurologic symptoms. A baseline post-treatment MRI scan of the head and neck was obtained within 2–6 months after completion of treatment, and then yearly or when clinically indicated. Patient follow-up was reported to the date last seen in clinic or to the date of expiration.

The endpoints analyzed were overall survival, local control, and distant metastasis-free survival. All events were measured from the first day of treatment. Local control was attained if there was no evidence of tumor growth at the primary site according to clinical and radiographic findings at follow-up. Median follow-up among surviving patients was 14 months (range, 1–97 months). Actuarial estimates of overall survival, local control, and distant metastases-free survival were calculated using the Kaplan–Meier method, with comparisons among groups performed with two-sided log–rank tests. All tests were two-tailed, with a probability value of < 0.05 considered statistically significant.

2.1

Patients

The medical records of 16 consecutive patients treated for newly-diagnosed SNUC of the head and neck between November 1999 and May 2009 were analyzed. Immunohistochemical staining, using a wide variety of markers including cytokeratin, vimentin, neuron-specific enolase, chromogranin, synatophysin, and/or S-100 was performed on all specimens to confirm the diagnostic entity. The median age of all patients was 50 years (range, 36–80 years). Fourteen men and two women were included. All patients underwent pre-treatment physical examination with direct nasopharyngolaryngoscopy and basic laboratory work including complete blood count, liver function tests, and electrolytes. Imaging consisted of computed tomography (CT) and magnetic resonance imaging (MRI) of the head and neck. Four patients (25%) underwent positron emission tomography prior to treatment. No patient had evidence of distant metastasis at initial diagnosis. All patients had locally advanced tumors at diagnosis, with 15 patients (94%) presenting as T4, and the remaining other patient having T3 disease, according to the 2009 American Joint Committee on Cancer (AJCC) staging classification. Four patients had clinically positive neck disease (4 level II, 1 level IB), all of whom were treated with non-surgical approaches. The primary sites were: maxillary sinus (7 patients), nasal cavity (5 patients), and ethmoid sinus (4 patients). This study was approved by all relevant Institutional Review Boards prior to the initiation of data collection.

2.2

Treatment

All patients were presented at a multi-disciplinary tumor conference at initial diagnosis for discussion about management. Treatment strategies were as follows: surgery alone (6 patients); surgery with post-operative radiation therapy with concurrent chemotherapy (4 patients); and non-surgical treatment of definitive radiation therapy with concurrent chemotherapy (6 patients). Generalized criteria for operability were established at the discretion of the surgeon. The surgical approach varied depending on tumor site, extent of disease, and physician expertise. In general, an attempt was made to maximize local control with preservation of cosmetic and functional outcome, while considering the medical comorbidities of the patient. Gross total resection with negative pathological margins was obtained in all patients who underwent surgery.

Radiation therapy technique varied depending on the site of disease, the time period of treatment, and the discretion of the radiation oncologist. All patients were treated with megavoltage equipment using photons or mixed photons and electrons. The clinical target volume was designed to cover the primary tumor site as defined by CT and/or MRI, considering physical examination findings, pathological findings, and the potential for microscopic extension. This typically included both halves of the nasal cavity and ipsilateral maxillary sinus extending to the medial wall of the orbit. Median doses were 60 Gy and 70 Gy in the postoperative and definitive settings, respectively, delivered at standard, once-daily fractionation. Seven patients received intensity-modulated radiotherapy. Concurrent chemotherapy regimens included cisplatin alone (4 patients) and cisplatin and etoposide (4 patients), carboplatin and paclitaxel (2 patients).

Treatment of the neck depended on multiple factors. All patients with clinical and/or radiographic evidence of cervical lymphadenopathy were treated with non-surgical therapy consisting of chemoradiotherapy with target volumes that included the ipsilateral neck. Among patients with clinically N0 disease, elective neck dissection was performed in 4 of 10 surgically-treated patients, with none having pathological evidence of disease. The use of elective neck irradiation after definitive surgery was administered at the discretion of the treating radiation oncologist and was performed in all but 1 case. The prophylactic dose to the uninvolved neck was typically 50–60 Gy.

2.3

Follow-up and statistical analysis

Patients were evaluated every 1 to 2 months during the first year after completion of treatment, every 3 months during the subsequent 6–12 months, every 4–6 months until 3 years post-treatment, and annually thereafter. Follow-up consisted of routine physical examination and review of systems, focusing particularly on the head and neck as well as the presence or absence of neurologic symptoms. A baseline post-treatment MRI scan of the head and neck was obtained within 2–6 months after completion of treatment, and then yearly or when clinically indicated. Patient follow-up was reported to the date last seen in clinic or to the date of expiration.

The endpoints analyzed were overall survival, local control, and distant metastasis-free survival. All events were measured from the first day of treatment. Local control was attained if there was no evidence of tumor growth at the primary site according to clinical and radiographic findings at follow-up. Median follow-up among surviving patients was 14 months (range, 1–97 months). Actuarial estimates of overall survival, local control, and distant metastases-free survival were calculated using the Kaplan–Meier method, with comparisons among groups performed with two-sided log–rank tests. All tests were two-tailed, with a probability value of < 0.05 considered statistically significant.