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


METHODS
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.


CONCLUSIONS
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.
Denis
Fabrice
F
Clinique d'Oncologie et de Radiothérapie, Centre Hospitalier Universitaire, Tours, France. fcdenis@club-internet.fr
Garaud
Pascal
P
Bardet
Etienne
E
Alfonsi
Marc
M
Sire
Christian
C
Germain
Thierry
T
Bergerot
Philippe
P
Rhein
Béatrix
B
Tortochaux
Jacques
J
Oudinot
Patrick
P
Calais
Gilles
G
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D003131:Combined Modality Therapy; D006801:Humans; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D011446:Prospective Studies; D011878:Radiotherapy / Q000009:adverse effects*; D015996:Survival Rate