Accelerated postoperative radiotherapy with weekly concomitant boost in patients with locally advanced head and neck cancer☆
Introduction
Locoregional control (LRC) is currently the most important issue in the treatment of locally advanced head and neck cancer (LAHNC) [20], and combination of surgery and postoperative radiotherapy (PORT) is traditionally applied without the support of any randomized study [18]. Doses of 50–66 Gy in 5–7 weeks are accepted as the ‘standard’ therapeutic modality, with experience showing that the locoregional relapse rate is decreased by 50% with a final LRC of 70–80% [29], [36].
Prognostic factors influencing LRC include site and stage of the primary tumor, type of surgery, pathological findings, total RT dose, and interval between surgery and PORT [11], [19], [22], [28], [33]. Patients with positive surgical margins, perineural infiltration, or lymph node involvement with or without extracapsular nodal extension (ENE) constitute a subgroup of patients with a high risk of locoregional relapse (up to 30%) when treated with conventional RT doses [1], [2], [7], [8], [24].
In order to improve the outcome, two major approaches can be proposed. The first is to combine concomitant chemotherapy and PORT. The European Organization for Research and Treatment of Cancer (EORTC) group and the Radiation Therapy Oncology Group (RTOG) have both recently conducted randomized phase III trials comparing this approach with standard PORT [7], [8]. The EORTC 22931 study showed an improved LRC, disease-free survival (DFS), and overall survival (OS) at 3 years with the combined treatment modality. However, RTOG 10-95 study failed to show a significant difference in terms of OS whereas 2-year DFS was improved by the combined modality. The second approach, based on radiobiological concepts, involves using altered fractionation, namely accelerated RT, in order to minimize tumor repopulation, which is one of the recognized factors in LRC in LAHNC [25], [37].
There is little data in the literature concerning the role of accelerated RT in the postoperative setting [3], [4], [30], [31], [34], [35]. Starting in December 1997, we prospectively proposed a slightly accelerated PORT as an alternative option to patients refusing to participate in or ineligible for the EORTC 22931 protocol, in which our institution actively participated [7].
Section snippets
Eligibility criteria
From December 1997 to December 2002, 89 patients with LAHNC treated with surgery were enrolled in a prospective study in the Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne. Inclusion criteria consisted of non-metastatic LAHNC with high locoregional relapse risk, 18 years or older, no previous history of cancer other than non-melanoma skin cancer or in situ cervix cancer, and good performance status (WHO scale 0–1). Exclusion criteria included gross residual disease after surgery,
Results
All but one patient (who terminated treatment at 56 Gy for non-treatment-related reasons) received the planned total dose (66 Gy). After a median follow-up period of 21 months (range 2–59), 59 of 89 patients were alive with (n=4) or without (n=55) evidence of disease. Median time to locoregional relapse was 10 months (range 2–21); only 4 local (4%) and 9 (10%) regional relapses were observed. Median time to isolated local relapse was 10 months. Median time to distant metastasis (n=18) was 15
Discussion
Several altered fractionation techniques have been developed for LAHNC, including hyperfractionated RT, accelerated RT, the combination of those two modalities, and continuous hyperfractionated accelerated RT (CHART) [6].
The total treatment duration is a well-recognized factor influencing the outcome in head and neck cancer [21]. Several randomized studies have compared conventionally fractionated RT with accelerated RT for variously located LAHNC without curative surgery [12], [13], [14], [16]
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Presented at the 12th European Cancer Conference, Copenhagen, September 21–25, 2003, and at the 45th Annual Meeting of the American Society for Therapeutic Radiology and Oncology, Salt Lake City, October 19–23, 2003.