Optimized therapy strategies for locally advanced adenoid cystic carcinomas using modern radiation therapy techniques

Abstract

To evaluate whether modern photon techniques such as fractionated stereotactic radiation therapy (FSRT) or stereotactically guided intensity modulated photon radiation therapy (IMRT) outweigh the biologic advantages of high-LET RT such as carbon ion RT in the treatment of locally advanced adenoid cystic carcinomas. Into our study we included 63 patients with macroscopic tumor residual after surgery or inoperable adenoid cystic carcinomas treated with modern RT techniques at the University of Heidelberg. Locoregional control, disease free survival and overall survival rates achieved with modern photon techniques alone were compared to the results obtained with combined photon RT and a carbon ion boost. Since September 1998, 29 patients with locally advanced adenoid cystic carcinomas have been treated with a combination of 45 to 54 Gy of photon RT (FSRT or IMRT) and a carbon ion boost of 18 GyE. The median dose to the macroscopic tumor was 72 GyE (63 to 72 GyE) for this patient group. Since carbon ion RT at the Heavy Ion Research Center (GSI) is available within 3 beam time blocks each year only, it was our institutional policy to treat patients with carbon ions only, if presentation of the patient allowed initiation of the treatment within 6 weeks. Patients who would have had to wait for carbon ion RT longer than 6 weeks, were offered photon RT using FSRT or IMRT alone. Between June 1995 and August 2003, thirty-four patients received high dose photon RT alone using FSRT (n = 13) or IMRT (n = 21) with a median total tumor dose of 66 Gy (range 54 to 70.4 Gy) to the macroscopic tumor. Inversely planned IMRT (step-and-shoot technique) was preferred for complex shaped targets since December 1999. Dose escalation within the macroscopic tumor was realized according to the integrated boost concept. Tumor stages and age of the patients were comparable for the different patient groups. Median follow-up was 16 months for patients treated with combined photon and carbon ion RT and 24 months (30 months for FSRT and 18 months for IMRT) for patients treated with FSRT or IMRT alone. Median GTV was comparable for both groups. Actuarial locoregional control rates at 4 years were 77.5% for combined photon and carbon ion RT and 24.6% for modern photon RT alone. However, the difference was not statistically significant (p = 0.08 log rank). Disease free survival rates and overall survival rates at 4 years were comparable with 53% and 75% for combined photon and carbon ion RT and 23% and 81% for photon RT alone, respectively. Rates for late toxicity CTC grade 3 were lower than 5% for both groups. We did not observe CTC grade 4 or 5 late toxicity. Modern RT techniques such as photon FSRT, IMRT or carbon ion RT allow a safe delivery of high target doses to locally advanced adenoid cystic carcinomas. Late toxicity rates can be kept lower as compared to the historic neutron therapy data. A combination of modern photon RT and carbon ion RT seems to be advantageous showing a trend towards higher rates of locoregional control as compared to photon RT alone. However, the difference was not statistically significant and bias can not be excluded as this was not a randomized trial. A randomized clinical trial comparing photon IMRT alone with combined photon IMRT and carbon ion RT as a standard arm is warranted