Elsevier

Radiotherapy and Oncology

Volume 70, Issue 2, February 2004, Pages 183-188
Radiotherapy and Oncology

Accelerated postoperative radiotherapy with weekly concomitant boost in patients with locally advanced head and neck cancer

https://doi.org/10.1016/j.radonc.2003.11.007Get rights and content

Abstract

Background and purpose: To assess the feasibility and efficacy of accelerated 66-Gy postoperative radiotherapy (PORT) using a single-fraction regimen from Mondays to Thursdays and a concomitant boost on Friday afternoon sessions in patients with locally advanced head and neck cancer (LAHNC).

Patients and methods: Between December 1997 and June 2002, 89 consecutive patients with pT1–pT4 and/or pN0–pN3 LAHNC were included. PORT was indicated in patients with positive surgical margins, T4 tumors, or extracapsular nodal infiltration. RT consisted of 66 Gy (2 Gy/fr) in 5 weeks and 3 days. Median follow-up was 21 months (range 2–59).

Results: Acute morbidity was acceptable: grade 3 mucositis in 20 (22%) patients, grade 3 dysphagia in 22 (25%) patients, and grade 3 skin erythema in 18 (20%) patients. Median weight loss was 2 kg (range 0–14.5). No grade 4 toxicity was observed. Late effects included grade 3 xerostomia in 6 (7%) patients, and grade 3 edema in 2 (2%) patients. Median time to locoregional relapse was 10 months (range 2–21). Two-year overall, cause-specific, and disease-free survival rates were 70% (95% confidence interval (CI) 59–81), 75% (95% CI 64–86), and 63% (95% CI 52–74), respectively. The 2-year actuarial locoregional control rate was 80% (95% CI 70–90). Distant metastasis probability at 4 years was 38% (95% CI 20–56). Multivariate analysis revealed that pT-classification (pT1–2 vs. pT3–4) and extranodal extension (0, 1 vs. 2 or more) were the two factors independently influencing the outcome.

Conclusions: We conclude that reducing the overall treatment time using an accelerated PORT schedule including a once-weekly concomitant boost (six fractions per week) is easily feasible with excellent local control. Acute and late RT-related morbidity is acceptable. Given the disease progression pattern (distant metastases), adjuvant chemotherapy should be considered.

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]

References (37)

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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.

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