Clinical investigation: head and neck
Late toxicity results of the GORTEC 94-01 randomized trial comparing radiotherapy with concomitant radiochemotherapy for advanced-stage oropharynx carcinoma: comparison of LENT/SOMA, RTOG/EORTC, and NCI-CTC scoring systems

https://doi.org/10.1016/S0360-3016(02)03819-1Get rights and content

Abstract

Purpose: To prospectively assess 5-year late toxicity in patients treated by concomitant radiochemotherapy for locally advanced oropharynx carcinoma using three different toxicity scales.

Methods and Materials: A total of 226 patients were entered in a Phase III multicenter, randomized trial comparing radiotherapy alone (70 Gy in 35 fractions: Arm A) with concomitant radiochemotherapy (70 Gy in 35 fractions with three cycles of a 4-day regimen containing carboplatin and 5-fluorouracil: Arm B). Five living patients, free of local or distant recurrences, could not be evaluated for late toxicity. Forty-four patients were eligible for late toxicity with a median follow-up of 5 years. Late toxicity was evaluated by the radiation oncologist using a large questionnaire containing 120 mixed items of three scales (NCI-CTC, LENT/SOMA, and RTOG). The data were then transposed on separate scales using corresponding grades.

Results: The 5-year overall survival rate was 22% in Arm B and 16% in Arm A (p = 0.05). The 5-year locoregional control rate was 48% in Arm B and 25% in Arm A (p = 0.002). The spinal cord was not affected by the concomitant adjunct of chemotherapy, and no deaths were caused by late toxicity. Using the three late toxicity scales, 100% of the patients treated with the combined modality (Arm B) developed one or more late complications vs. 94% in the radiotherapy-alone arm (Arm A). The difference was not statistically significant. The most commonly damaged organs (all Grade 1–4) were the salivary glands (100% in Arm B vs. 82% in Arm A, p <0.05), skin (78% vs. 47%, p <0.05), teeth (67% vs. 18%, p <0.05), mucosa (59% vs. 63% p = not significant), and mandible (44% vs. 12%, p <0.05). One or more Grade 3–4 complications occurred in 82% of the patients in Arm B vs. 47% in Arm A (p = 0.02) but concerned only the teeth. The correlation between the RTOG and LENT/SOMA scale and between the NCI-CTC and LENT/SOMA scale were low for Grade 1–4 toxicity (near 30%). The transposability of a patient’s symptoms was significantly greater using the LENT/SOMA or RTOG/EORTC scaling systems than using the NCI-CTC system.

Conclusion: Concomitant radiochemotherapy increased overall survival and locoregional control rates. The difference between the two treatment groups for Grade 3–4 complications was only significant for the teeth. The late toxicity assessment of a treatment may depend on the toxicity scale used. The LENT/SOMA scale seems to be the most accurate scale, but most of the score results were not concordant with those obtained with other scales. The results of this study confirm the necessity of using a common late toxicity scale in clinical trials.

Introduction

Most oropharyngeal carcinomas are locally advanced at presentation 1, 2. Thus, patients are often treated using radiotherapy (RT), but the results are poor. In 1994, the French Head and Neck Oncology and Radiotherapy Group (GORTEC) initiated a randomized, Phase III, multicenter clinical trial to evaluate prospectively the benefit of a concomitant radiochemotherapy schedule vs. RT alone for advanced-stage oropharynx carcinoma. The combined modality treatment led to increased 3- and 5-year overall survival rates and 3- and 5-year locoregional control rates 3, 4. However, normal tissue radiation late effects remain a major problem for long-term surviving patients. In head-and-neck cancer, radiation late toxicity was usually assessed using the National Cancer Institute (NCI) or the Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) scale (5). Then, it was proposed to replace all late toxicity scales with the Late Effect Normal Tissue Task Force (LENT)/subjective, objective, management, analytic (SOMA) scale resulting from an international collaboration between the EORTC and RTOG subcommittees to standardized the toxic effects criteria (6). The purpose of this study was to assess prospectively the late toxic effects observed when patients are treated with RT alone or RT and concomitant chemotherapy. This analysis was performed using the three different toxicity scales (LENT/SOMA, NCI-Common Toxicity Criteria [CTC], and RTOG/EORTC) simultaneously. The accuracy and concordance of these scales were evaluated.

Section snippets

Study design

Patients were included in the study if all the following criteria were met: invasive squamous cell carcinoma of the oropharynx (Stage III or IV, without evidence of distant metastases), <75 years old, and Karnofsky performance score of ≥60. Patients were excluded if they had previously undergone treatment for this disease or any other cancer (except basal cell carcinoma of the skin) or if they had synchronous primary lesions. Other criteria for inclusion included a neutrophil count >1500

Toxicity scale comparison

In the combined-modality arm (Arm B), 27 patients were alive at 5 years; in the RT-alone arm (Arm A) 17 were alive. Thus, 44 questionnaires were studied to compare the toxicity scales with each other.

Transposability of patients’ symptoms to toxicity items

Ninety Grade 1–4 toxic events were assessed using the RTOG/EORTC combined with the LENT/SOMA scale. Seventy-four percent of the events were found using only the RTOG/EORTC scale and 80% were found using only the LENT/SOMA scale (p = not significant).

Eighty-four Grade 1–4 toxic events were assessed

Discussion

In this prospective study, we compared three toxicity scales to assess prospectively the late toxicity rate of a concomitant chemoradiation schedule vs. RT alone for locally advanced oropharynx carcinoma. We first found that the transposability of patients’ symptoms was significantly higher using the LENT/SOMA or RTOG/EORTC scaling systems than using the NCI-CTC system. The LENT-SOMA had the best transposability rate for all but one organ damage (salivary glands). For this toxicity, the

Conclusion

Concomitant chemoradiation for locally advanced oropharynx carcinoma increased the overall survival rate and locoregional control rate but did not increase severe complications. The late toxicity assessment of a treatment may depend on the toxicity scale used, confirming the necessity of using a common late toxicity scale in clinical trials.

Acknowledgements

Other authors included the following: Dr. Alavena (Avignon), Dr. Ardiet (Lyon Sud), Dr. Auregan (Bourges), Dr. Cailleux (Tours), Dr. Chaib-Rassou (Metz), Dr. Delpon (Le Mans), Dr. Desprez (Vannes), Dr. Favre (Orléans), Dr. Hardiet (Lyon), Dr. Maillard (Angers), Dr. Oudinot (Le Havre), Dr. Raoul (St. Grégoire), and Dr. Gesta (Niort).

Cited by (0)

View full text