Abstract
Purpose
The aim of the study was to determine the prognostic impact of preepiglottic space (PES) involvement on local failure after concurrent chemoradiation therapy for squamous cell carcinoma.
Materials and methods
Retrospective chart review of patients who underwent concurrent chemoradiation therapy for T3 or T4 laryngeal, T4 hypopharyngeal, and T3 or T4 oropharyngeal squamous cell carcinoma were eligible for inclusion. Patients were then stratified by the presence or absence of PES tumor involvement. A multivariate analysis was performed on the presence of recurrence using the following pretreatment variables: PES involvement, tumor extent, pathologic cell differentiation, lymph node involvement, age, and sex.
Results
A total of 102 patients were included in the study. Twenty-seven (28%) patients had documented PES involvement. Mean follow-up for all patients was 46 months. Involvement of the PES was not significantly associated with local tumor persistence or recurrence ( P = .69). No other variables significantly impacted tumor recurrence.
Conclusion
Preepiglottic space involvement does not negatively impact local tumor control after concurrent chemoradiation therapy.
1
Introduction
The treatment of head and neck squamous cell carcinoma has evolved significantly for the past several decades. One such advancement has been the development of organ preservation protocols using concurrent chemoradiation therapy. Concurrent chemoradiation therapy has been used at the Cleveland Clinic (Cleveland, OH) for treatment of select patients with advanced squamous cell carcinoma of the head and neck since 1989. The addition of chemotherapy to definitive radiation therapy delivered in a concomitant fashion has been shown to produce a significant benefit in locoregional control and survival . Most clinical trials have included patients with advanced tumors arising from multiple head and neck subsites, but there appears to be little available data on tumor response involving specific anatomical regions such as the preepiglottic space (PES) .
Involvement of the PES signifies advancement of a tumor into a discreet anatomical region sequestered by fibroelastic and cartilaginous tumor barriers . The preepiglottic space was first described by Boyer in the late 1700s who considered the region function as a prethyrohyoid bursa. It is separated from mucosal surfaces of the head and neck by the hyoepiglottic ligament superiorly, the thyrohyoid membrane anteriorly, and the anterior surface of the epiglottis and thyroepiglottic ligaments posteroinferiorly ( Fig. 1 ). These boundaries demarcate a relatively avascular, inverted pyramid-shaped space that contains lymphatics, fat, and loose areolar tissue . Invasion of tumor into such a sequestered avascular space signifies advanced disease that may be difficult to eliminate by radiation therapy, which is in part dependent on adequate tissue oxygenation.
In supraglottic carcinomas, PES invasion is sufficient for at least a T3 tumor classification. Indeed, some authors have argued that PES invasion should justify T4 classification . Ljumanovic reported that PES involvement in patients with supraglottic tumors is predictive of local recurrence in patients treated with definitive radiation therapy alone. Furthermore, given its location and the expected inflammatory response that occurs with radiation treatment, tumor status in the PES is difficult to evaluate after completion of such therapy, making assessment of clinical response difficult. To the best of our knowledge, no study has evaluated the prognostic impact of PES invasion in patients with advanced squamous cell carcinoma treated with definitive concurrent chemoradiation therapy. We hypothesize that PES involvement may portend a poor prognosis of local persistence or recurrence in patients undergoing concurrent chemoradiation therapy.
2
Materials and methods
All patients treated with definitive concurrent chemoradiation therapy at our institution are entered into an institutional review board-approved registry. An international review board-approved retrospective chart review was performed on all patients in this registry who had undergone treatment between 1989 and 2002. Patients who underwent concurrent chemoradiation therapy for T3 or T4 supraglottic laryngeal, T4 hypopharyngeal, and oropharyngeal squamous cell carcinoma were eligible for inclusion. These specific tumors were chosen for their potential involvement of the PES. Data were analyzed with respect to local tumor control before consideration of surgical salvage. The chemoradiation therapy treatment schedule included 4-day continuous infusions of 5-fluorouracil (1000 mg/m 2 per day) and cisplatin (20 mg/m 2 per day) during the first and fourth week of either once daily (QD) or twice daily (BID) conventional external beam radiation therapy. Patients receiving QD treatments received standard fractions of 1.8 to 2.0 Gy, to a total dose of 66 to 72 Gy. Patients receiving BID treatments received twice daily fractions of 1.2 Gy to a total dose of 72 Gy. Patients were then sorted by the presence or absence of PES tumor involvement. For those patients with PES involvement, further analysis was performed to determine either major or minor tumor involvement. Major involvement was defined as radiographic PES involvement ( Fig. 2 ) with tumor palpable on examination under anesthesia. Minor PES involvement was defined as radiographic evidence without palpable tumor on examination under anesthesia. The main outcome measure was local tumor control, and the length of follow-up was also recorded.
2
Materials and methods
All patients treated with definitive concurrent chemoradiation therapy at our institution are entered into an institutional review board-approved registry. An international review board-approved retrospective chart review was performed on all patients in this registry who had undergone treatment between 1989 and 2002. Patients who underwent concurrent chemoradiation therapy for T3 or T4 supraglottic laryngeal, T4 hypopharyngeal, and oropharyngeal squamous cell carcinoma were eligible for inclusion. These specific tumors were chosen for their potential involvement of the PES. Data were analyzed with respect to local tumor control before consideration of surgical salvage. The chemoradiation therapy treatment schedule included 4-day continuous infusions of 5-fluorouracil (1000 mg/m 2 per day) and cisplatin (20 mg/m 2 per day) during the first and fourth week of either once daily (QD) or twice daily (BID) conventional external beam radiation therapy. Patients receiving QD treatments received standard fractions of 1.8 to 2.0 Gy, to a total dose of 66 to 72 Gy. Patients receiving BID treatments received twice daily fractions of 1.2 Gy to a total dose of 72 Gy. Patients were then sorted by the presence or absence of PES tumor involvement. For those patients with PES involvement, further analysis was performed to determine either major or minor tumor involvement. Major involvement was defined as radiographic PES involvement ( Fig. 2 ) with tumor palpable on examination under anesthesia. Minor PES involvement was defined as radiographic evidence without palpable tumor on examination under anesthesia. The main outcome measure was local tumor control, and the length of follow-up was also recorded.
3
Results
A total of 102 patients met inclusion criteria and were entered into the study. Four patients were lost to follow-up immediately after treatment, and 1 patient died during treatment of a pulmonary embolus. Thus, a total of 97 patients were able to be analyzed. There were 79 males and 18 females with an average age of 58 years. Mean follow-up for all patients was 46 months. Local persistence or recurrence of tumor was documented in 10 patients. One patient had radiologic findings suggestive of tumor recurrence, but the patient refused a biopsy. Eighty-six patients had local tumor control. Data regarding patient demographics, site of tumor, degree of differentiation, and radiation fractionation schedule are summarized in Table 1 and stratified according to the presence or absence of PES involvement. Twenty-seven (28%) patients had documented PES involvement as determined radiologically and/or clinically. Major preepiglottic involvement was found in 21 patients, whereas minor involvement was determined in 6 patients. There was no statistical difference ( P = .78) in mean follow-up between patients with and without PES involvement ( Table 2 ).
