Kate Johnson

April 24, 2013

GENEVA, Switzerland — A high-dose-rate interstitial brachytherapy boost after external-beam radiotherapy is associated with "acceptable" local control and overall survival in base-of-tongue cancer, according to a prospective phase 2 study.

"The low incidence of serious late side effects justifies the use of high-dose-rate interstitial brachytherapy as a local dose-escalation method," said lead author Zoltán Takácsi-Nagy, MD, from Bacs-Kiskun County Hospital in Kecskemét, Hungary.

He presented the results here at the 2nd European Society for Radiotherapy & Oncology (ESTRO) Forum.

The addition of chemotherapy to external-beam radiotherapy significantly improved results in this study, he noted. "The 5-year overall survival was significantly better (30%) in those who received radiochemotherapy than in those who received radiotherapy alone," he reported.

Although one expert said that brachytherapy is a good way of targeting these base-of-tongue cancers, another said he is "unconvinced" that it shows the benefit of a brachytherapy boost.

Small Prospective Study

Dr. Takácsi-Nagy and colleagues conducted a prospective study of 60 patients with T1–4 and N0–3 base-of-tongue carcinoma (mean age, 57 years) from January 1992 and June 2011. Median follow-up was 121 months.

In total, 93% of patients had advanced-stage (III/IV) disease, 60% with T4 and 29% with T3 cancers, he said.

Patients were initially treated with external-beam irradiation, and 17 (28%) received radiochemotherapy. The mean external-beam irradiation dose was 62 Gy, most frequently given as 5 fractions of 3 Gy or 5 fractions of 4 Gy, he explained.

External-beam irradiation was followed 2 to 6 weeks later with a high-dose-rate brachytherapy boost (mean dose, 17 Gy).

Two to 3 months after treatment, computed tomography or magnetic resonance imaging revealed that 46 patients (77%) had achieved complete remission and 14 (23%) had achieved partial remission.

Table. Five- and 10-Year Actuarial Rates for Outcomes

Outcomes 5-Year Rates, % 10-Year Rates, %
Local control 57 57
Locoregional control 50 50
Overall survival 47 35
Cancer-specific survival 61 61


Overall survival was significantly better in the patients who received radiochemotherapy than in those who received radiotherapy alone (69% vs 39%; = 0.005).

Delayed soft tissue ulceration occurred in 12% of patients, and osteoradionecrosis occurred in 1%, Dr. Takácsi-Nagy reported.

On multivariate analysis, N-stage (P < .001) and radiotherapy (= .003) were found to be a prognostic factors for overall survival, and N-stage was found to be a prognostic factor for cancer-specific survival (= .017).

"Further studies are needed to define the optimal dose and fractionation of high-dose-rate brachytherapy in the treatment of base-of-tongue cancer," he concluded.

One Expert "Unconvinced"

William Mendenhall, MD, professor of radiation oncology at the University of Florida College of Medicine in Gainesville, said that these new data leave him "unconvinced" of the benefits of brachytherapy boost. Dr. Mendenhall, who has published extensively on various radiotherapy techniques for oropharyngeal squamous cell carcinoma, was asked to comment on the findings by Medscape Medical News.

"There are no convincing data, including those reported by the authors, that a brachytherapy boost results in improved outcomes. In fact, their data suggest the reverse," he said.

"The outcomes reported by the authors are, if anything, worse than those reported after external-beam irradiation alone or combined with adjuvant chemotherapy," he noted, adding that "brachytherapy is likely more morbid and expensive."

Dr. Mendenhall and colleagues recently studied intensity-modulated radiotherapy in 160 patients with oropharyngeal squamous cell carcinoma, and found a lower rate of severe late complications than Dr. Takácsi-Nagy's team (8% vs 13%) (Laryngoscope. 2010;120:2218-2222).

Although the percentage of patients with late-stage disease was similar in the studies by Dr. Mendenhall's group and Dr. Takácsi-Nagy's group (90% vs 93%), Dr. Mendenhall's group had fewer T3/T4 cancers (36% vs 89%). In addition, Dr. Mendenhall showed better 5-year results for local control (87% vs 57%), locoregional control (84% vs 50%), overall survival (76% vs 47%), and cause-specific survival (85% vs 61%).

In an earlier study using definitive radiotherapy alone, Dr. Mendenhall and colleagues reported similarly superior results (Am J Clin Oncol. 2006;29:32-39).

He noted the high proportion of T4 tumors in the results presented by Dr. Takácsi-Nagy's. "These are likely not adequately covered by a brachytherapy boost," he explained.

Good Approach to Treatment

However, another expert, Eugene Myers, MD, professor and emeritus chair in the Department of Otolaryngology at the University of Pittsburgh Medical Center in Pennsylvania, said that "brachytherapy is a proven method of directly boosting the intensity of treatment at the particular target. We feel that this is a good way of treating this cancer," he told Medscape Medical News.

In a study of chemoradiation followed by brachytherapy for base-of-tongue squamous cell carcinoma (Head Neck. 2009;31:1431-1438), Dr. Myers and colleagues found results similar to those of Dr. Takácsi-Nagy's group. However, "our results are better with respect to the neck," he noted. "One important aspect is that in their study, they had more patients with advanced local cancer."

Dr. Myers' series included 37 patients with T1 and T2 tumors and 51 with T3 and T4 tumors. Cervical lymph node metastasis was present in 71 (80.7%). A brachytherapy boost delivered 5 weeks after chemoradiation resulted in a 3-year control rate of 87.5% in the primary site and of 93.2% in the neck, with a 3-year survival rate of 80.9%.

"We were very impressed with this program since, in addition to these results, there was also a decrease in morbidity from the treatments, in the sense that xerostomia was not as intense and very few patients developed trismus or soft or hard tissue necrosis," he said.

Dr. Takácsi-Nagy, Dr. Mendenhall, and Dr. Myers have disclosed no relevant financial relationships.

2nd European Society for Radiotherapy & Oncology (ESTRO) Forum: Abstract OC-0363. Presented April 21, 2013.


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