Summary of major radiation fractionation and chemotherapy trials for organ preservation therapy in locally advanced head and neck squamous cell carcinoma.

PURPOSE: To review radiation fractionation and chemotherapy trials for patients undergoing organ preservation therapy for locally advanced head and neck squamous cell carcinoma. METHODS AND MATERIALS: Radiation therapy fractionation and chemotherapy trial results as well as historical evidence are systematically reviewed. RESULTS: Trial results, which involve nearly 30,000 patients, have been interpreted, compared, and presented in a structured manner to demonstrate the changing approaches in treatment over the years from the 1960s to the present. The review includes data from the split-course radiation therapy era, meta-analyses of chemotherapy and radiation therapy fractionation trials, cetuximab trials, "triple-drug trials," and modern trials of induction chemotherapy followed by concomitant chemotherapy and radiation therapy. CONCLUSIONS: This summary will be useful to clinicians making treatment decisions today and to investigators designing trials in the future.

Neoadjuvant chemotherapy followed by concurrent hyperfractionated radiation therapy and sensitizing chemotherapy for locally advanced (T3-T4) oropharyngeal squamous cell carcinoma.

BACKGROUND: Radiation therapy (RT) is commonly used in the management of patients with advanced (T3-T4) oropharyngeal squamous cell carcinomas. In recent years, based upon the meta-analyses of randomized trials, chemotherapy administered concurrently with RT (chemoradiotherapy) has become the standard of care. Twice-a-day hyperfractionated or accelerated-fractionated RT regimens have been shown in a number of randomized trials to significantly improve the rate of local control compared with conventional once-a-day fractionation. Concurrent chemotherapy administered along with hyperfractionated or accelerated RT has been shown to add significant additional benefit over hyperfractionated or accelerated RT alone. Neoadjuvant chemotherapy (usually consisting of cisplatin and fluorouracil) also produces favorable responses in most patients (approximately 75% partial or complete response rates) with advanced head and neck cancer, but its role remains controversial. METHODS: The results of treatment of 23 patients with T3 or T4 oropharyngeal squamous cell carcinomas who received neoadjuvant chemotherapy, followed by hyperfractionated RT (120 cGy twice-a-day to 74.4-76.8 Gy) were retrospectively reviewed. The 14 patients who were most recently treated also received concurrent sensitizing doses of single agent chemotherapy, usually cisplatin. No patient was seen with distant metastasis, and all were treated with curative intent. Ten patients had T3 and 13 patients had T4 primary tumors. Three patients (13%) had stage III disease and 20 patients (87%) had stage IV disease. Ten patients had base of tongue primaries, 12 had tonsillar primaries, and 1 had an oropharyngeal wall primary. Eighteen patients (78%) had clinically involved neck nodes. RESULTS: Seventy-four percent of patients had partial (>50%) or complete response at the primary site following neoadjuvant chemotherapy. One patient died of cardiorespiratory arrest after the first cycle. Thirteen percent of patients had unplanned interruptions of their RT courses secondary to severe mucositis. Local control at the primary site (minimum 2 years follow-up) was achieved in 17 of 19 (89%) patients. Two- and 5-year absolute survival rates were 71% and 55%, respectively. No patient was gastrostomy dependent beyond 18 months. Four patients developed neck failure after RT alone and none was successfully salvaged. CONCLUSION: This study is noteworthy in that it uses both neoadjuvant and concurrent sensitizing chemotherapy along with hyperfractionated RT. There is little information in the literature on this approach. Although the regimen is somewhat toxic, it is less so than many other regimens, which combined full-dose multiagent chemotherapy during the course of RT. The latter regimens also have a significant incidence of permanent dysphagia, gastrostomy dependence, and/or aspiration, complications that were not encountered in this group. The local control rate was high (89%). We continue to recommend this regimen for patients with locally advanced head and neck squamous cell carcinomas.

Squamous cell carcinoma of the oropharynx: surgery, radiation therapy, or both.

BACKGROUND: 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. METHODS: Treatment results from North American academic institutions that used S with or without adjuvant RT (S +/- RT) or used RT alone or followed by neck dissection (RT +/- ND) for patients with SCC of the tonsillar region or the base of tongue were compiled through a MEDLINE search (from 1970 to August, 2000) and from the references cited in each report. Studies were eligible for inclusion if they contained direct, actuarial (life-table), or Kaplan-Meier calculations for the following end points: local control, local-regional control, 5-year absolute survival, 5-year cause specific survival, or severe or fatal treatment complications. Weighted average results, which took into account series size, were calculated for each end point for the purposes of treatment comparison. Results and conclusions were based on data from 51 reported series, representing the treatment of approximately 6400 patients from the United States and Canada. RESULTS: The results for patients with SCC of the base of tongue who underwent S +/- RT versus RT +/- ND, respectively, were as follows: local control, 79% versus 76% (P = 0.087); local-regional control, 60% versus 69% (P = 0.009); 5-year survival, 49% versus 52% (P = 0.2); 5-year cause specific survival, 62% versus 63% (P = 0.4); severe complications, 32% versus 3.8% (P < 0.001); and fatal complications, 3.5% versus 0.4% (P < 0.001). The results for patients with SCC in the tonsillar region who underwent S +/- RT versus RT +/- ND, respectively, were as follows: local control, 70% versus 68% (P = 0.2); local-regional control, 65% versus 69% (P = 0.1); 5-year survival, 47% versus 43% (P = 0.2); 5-year cause specific survival, 57% versus 59% (P = 0.3); severe complications, 23% versus 6% (P < 0.001); and fatal complications, 3.2% versus 0.8% (P < 0.001). CONCLUSIONS: The information in this article provides a useful benchmark for evidence-based counseling of patients with SCC of the oropharynx. The rates of local control, local-regional control, 5-year survival, and 5-year cause specific survival were similar for patients who underwent S +/- RT or RT +/- ND, whereas the rates of severe or fatal complications were significantly greater for the S +/- RT group. Furthermore, available data on the functional consequences of treatment suggest the superiority of RT +/- ND. The authors conclude that RT +/- ND is preferable for the majority of patients with SCC of the oropharynx.