Denis Fabrice, Garaud Pascal, Bardet Etienne, Alfonsi Marc, Sire Christian, Germain Thierry, Bergerot Philippe, Rhein Béatrix, Tortochaux Jacques, Oudinot Patrick, Calais Gilles
Clinique d'Oncologie et de Radiothérapie, Centre Hospitalier Universitaire, Tours, France.
Int J Radiat Oncol Biol Phys. 2003 Jan 1;55(1):93-8. doi: 10.1016/s0360-3016(02)03819-1.
To prospectively assess 5-year late toxicity in patients treated by concomitant radiochemotherapy for locally advanced oropharynx carcinoma using three different toxicity scales.
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.
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.
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.
使用三种不同的毒性量表对局部晚期口咽癌同步放化疗患者的5年迟发性毒性进行前瞻性评估。
共有226例患者进入一项III期多中心随机试验，比较单纯放疗（35次分割，70 Gy：A组）与同步放化疗（35次分割，70 Gy，联合三个周期含卡铂和5-氟尿嘧啶的4天方案：B组）。5例存活且无局部或远处复发的患者无法评估迟发性毒性。44例患者符合迟发性毒性评估标准，中位随访时间为5年。放射肿瘤学家使用一份包含120项混合内容的大问卷对迟发性毒性进行评估，该问卷涵盖三种量表（美国国立癌症研究所常见毒性标准（NCI-CTC）、晚期效应正常组织不良反应评价标准（LENT/SOMA）和美国放射肿瘤学会（RTOG））。然后将数据按照相应等级转换到各自的量表上。
B组5年总生存率为22%，A组为16%（p = 0.05）。B组5年局部区域控制率为48%，A组为25%（p = 0.002）。脊髓未受同步化疗的影响，且无迟发性毒性导致的死亡。使用三种迟发性毒性量表评估，联合治疗组（B组）1（）%的患者出现一种或多种迟发性并发症，而单纯放疗组（A组）为94%。差异无统计学意义。最常受损的器官（所有1 - 4级）为唾液腺（B组100%，A组82%，p <0.05）、皮肤（78%对47%，p <0.05）、牙齿（67%对18%，p <0.05）、黏膜（59%对63%，p无统计学意义）和下颌骨（44%对12%，p <0.05）。B组82%的患者发生一种或多种3 - 4级并发症，A组为47%（p = 0.02），但仅涉及牙齿。对于1 - 4级毒性，RTOG与LENT/SOMA量表之间以及NCI-CTC与LENT/SOMA量表之间的相关性较低（接近30%）。使用LENT/SOMA或RTOG/EORTC量表系统时，患者症状的可转换性明显高于使用NCI-CTC系统。
同步放化疗提高了总生存率和局部区域控制率。两个治疗组在3 - 4级并发症方面的差异仅在牙齿方面具有统计学意义。治疗的迟发性毒性评估可能取决于所使用的毒性量表。LENT/SOMA量表似乎是最准确的量表，但大多数评分结果与其他量表不一致。本研究结果证实了在临床试验中使用通用迟发性毒性量表的必要性。
