International Journal of Radiation Oncology*Biology*Physics
Clinical investigation: head and neckFeasibility and toxicity of combined photon and carbon ion radiotherapy for locally advanced adenoid cystic carcinomas
Introduction
Adenoid cystic carcinomas (ACC) are rare salivary gland malignancies with an infiltrative growth pattern and a propensity for perineural spread. Surgical resection is considered the treatment of choice, but complete resection is exceptional for locally advanced ACC in the head-and-neck region. Postoperative irradiation is generally accepted as adjunct to surgery in a multimodal therapy approach. After complete and marginal resection, adjuvant radiation therapy (RT) improves locoregional control and overall survival rates. Actuarial local control rates after 5 years are reported to be as high as 95% after complete resection of malignant salivary gland tumors followed by irradiation with tumor doses in the range of 50 to 69 Gy (1). Clinical studies showed that skull base involvement and gross residual disease or inoperability have a negative impact on local control probability and overall survival even after radiotherapy (2). Local control rates after conventional low-LET (linear energy transfer) RT are suboptimal in patients with locally advanced ACC 3, 4. Vikram et al. obtained locoregional control in less than 10% of 49 patients treated with conventional RT for recurrent and unresectable ACC (4).
Several clinical trials were performed to investigate the role of high-LET radiotherapy such as fast neutrons for ACC. Several nonrandomized and randomized prospective trials proved the superiority of fast neutron RT over conventional low-LET RT for malignant salivary gland tumors 5, 6, 7. A main disadvantage of neutron RT is the relatively high rate of severe late effects 8, 9, 10.
Since December 1997, carbon ion therapy has been available for patient treatments at the heavy ion synchrotron (SIS) at the Heavy Ion Research Center (GSI) in Darmstadt, Germany. Carbon ions provide physical selectivity represented by an inverse dose profile (11). Additionally, carbon ion beams are expected to provide enhanced relative biologic effectiveness (RBE) in the target volume similar to neutron RT in ACC. But in the entrance channel dose and RBE are much lower compared with the neutrons. The raster scan system used for intensity-controlled beam delivery further improves target coverage and sparing of normal tissue and restricts the highly efficient part of the carbon beam to the target volume only (12). This is achieved by the integration of a biology-based optimization for treatment planning which represents a further gain in treatment quality 13, 14, 15, 16.
Simultaneous to developments in the field of carbon ion RT during the last few years, innovations in treatment planning and accelerator technology such as inverse treatment planning and intensity-modulated radiotherapy have widened the therapeutic window of photon RT and enabled dose escalation.
Within the German Heavy Ion Pilot Project, a feasibility project was started in 1998. Seventy patients with skull base tumors such as chordomas, low-grade chondrosarcomas, and ACC have been treated with carbon ions. In January 2001, a clinical Phase I/II study was begun to investigate combined photon RT and carbon ion RT for locally advanced ACC.
This report summarizes our first experience in the treatment of locally advanced ACC with combined photon RT and a carbon ion boost within a prospective trial.
Section snippets
Patient characteristics
Between September 1998 and April 2002, 16 patients with ACC of the head-and-neck region were treated with combined photon RT and a carbon ion boost to the macroscopic tumor. There were 9 female and 7 male patients. Median age at the time of RT was 56 years (range 25 to 76 years). All patients had histopathologically proven ACC. Eight of 16 patients (50%) showed a solid subtype. Perineural spread was diagnosed in 7 patients (43.7%). Eligibility criteria were histology of an ACC; the presence of
Feasibility
Median follow-up was 12 months (range 3–43) at the time of analysis. All patients completed the intended treatment. Five of 6 patients treated with combined fractionated stereotactic photon RT and carbon ions received a reduced photon dose of 45 to 52.2 Gy to respect the tolerance doses of neighboring organs at risk. Using photon IMRT, the desired target dose of 54 Gy to the CTV could be achieved in all 10 patients and enabled the delivery of a carbon ion boost with 18 GyE while respecting the
Discussion
Although the study primarily aimed at the evaluation of feasibility of combined photon RT with a carbon ion boost and follow-up is still short, the utilized therapy already resulted in relatively high local control rates. In our series, combined photon RT with a carbon ion boost resulted in local control rates at 80.8% and 64.6% at 1 and 3 years, which are comparable to the control rates obtained with neutron therapy alone in most of the reported trials. Furthermore, local control rates at 3
Conclusions
Our preliminary data indicate that combined photon RT and carbon ion boost is feasible and effective in the treatment of locally advanced ACC with unfavorable prognostic factors such as skull base involvement and macroscopic tumor residual. We did not observe severe late effects. Local control rates at 3 years appear to be comparable with local control rates reported after fast neutron RT, but a longer follow-up is needed to prove these initial results. A clinical Phase III study is warranted.
Acknowledgements
The authors wish to thank S. Kuhn, A. Miltner, E. Rittinghausen, and K. Kuhn for their excellent technical support.
References (39)
- et al.
The influence of positive margins and nerve invasion in adenoid cystic carcinoma of the head and neck treated with surgery and radiation
Int J Radiat Oncol Biol Phys
(1995) - et al.
Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy
Int J Radiat Oncol Biol Phys
(2000) - et al.
Radiation therapy in adenoid cystic carcinoma
Int J Radiat Oncol Biol Phys
(1984) - et al.
Radiotherapy for advanced adenoid cystic carcinomaNeutrons, photons and mixed beam?
Radiother Oncol
(2001) - et al.
Neutron versus photon irradiation for unresectable salivary gland tumors. Final report of an RTOG-MRC randomized clinical trial. Radiation Therapy Oncology Group Medical Research Council
Int J Radiat Oncol Biol Phys
(1993) - et al.
The implications of improved treatment of malignant salivary gland tumors by fast neutron radiotherapy
Int J Radiat Oncol Biol Phys
(1987) - et al.
Magnetic scanning system for heavy ion therapy
Nucl Instrum Meth
(1993) - et al.
Three dimensional accuracy and interfractional reproducibility of patient fixation using a stereotactic head mask system
Int J Radiat Oncol Biol Phys
(2001) - et al.
Stereotactically guided fractionated radiotherapyTechnical aspects
Radiother Oncol
(1993) - et al.
Inverse planning for photon and proton beams
Med Dosimetry
(2001)