Phase I/II trial evaluating carbon ion radiotherapy for the treatment of recurrent rectal cancer: the PANDORA-01 trial.
BMC cancer 12 (2012) 137
Abstract:
Background
Treatment standard for patients with rectal cancer depends on the initial staging and includes surgical resection, radiotherapy as well as chemotherapy. For stage II and III tumors, radiochemotherapy should be performed in addition to surgery, preferentially as preoperative radiochemotherapy or as short-course hypofractionated radiation. Advances in surgical approaches, especially the establishment of the total mesorectal excision (TME) in combination with sophisticated radiation and chemotherapy have reduced local recurrence rates to only few percent. However, due to the high incidence of rectal cancer, still a high absolute number of patients present with recurrent rectal carcinomas, and effective treatment is therefore needed.Carbon ions offer physical and biological advantages. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increase relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the cell line as well as the endpoint analyzed.Japanese data on the treatment of patients with recurrent rectal cancer previously not treated with radiation therapy have shown local control rates of carbon ion treatment superior to those of surgery. Therefore, this treatment concept should also be evaluated for recurrences after radiotherapy, when dose application using conventional photons is limited. Moreover, these patients are likely to benefit from the enhanced biological efficacy of carbon ions.Methods and design
In the current Phase I/II-PANDORA-01-Study the recommended dose of carbon ion radiotherapy for recurrent rectal cancer will be determined in the Phase I part, and feasibilty and progression-free survival will be assessed in the Phase II part of the study.Within the Phase I part, increasing doses from 12 × 3 Gy E to 18 × 3 Gy E will be applied.The primary endpoint in the Phase I part is toxicity, the primary endpoint in the Phase II part is progression-free survival.Discussion
With conventional photon irradiation treatment of recurrent rectal cancer is limited, and the clinical effect is only moderate. With carbon ions, an improved outcome can be expected due to the physical and biological characteristics of the carbon ion beam. However, the optimal dose applicable in this clincial situation as re-irradiation still has to be determined. This, as well as efficacy, is to be evaluated in the present Phase I/II trial.Trial registration
NCT01528683.Simulations of microdosimetric quantities with the Monte Carlo code FLUKA for carbon ions at therapeutic energies.
International journal of radiation biology 88:1-2 (2012) 176-182
Abstract:
Purpose
Microdosimetric quantities can be used to estimate the biological effectiveness of radiation fields. This study evaluates the capability of the general-purpose Monte Carlo code FLUKA to simulate microscopic patterns of energy depositions for mixed radiation fields which are created by carbon ions at therapeutic energies in phantoms.Materials and methods
Measured lineal energy spectra and linear energy transfer (LET) spectra produced by carbon ions of about 300 MeV/n at different depths in phantoms representing human tissue were chosen from published literature and were compared with results from simulations of the measurement set-ups with FLUKA.Results
Simulations of the dose-weighted lineal energy spectra yd(y) and dose-weighted LET spectra describe the main features of the respective measured spectra. All simulated frequency mean and dose mean lineal energy values are, respectively, within 21% and 11% of the measured ones. A slight underestimation of fragment fluences is notable. It is shown that the simultaneous detection of several charged fragments in the TEPC ('V effect') has considerable impact on the measured lineal energy spectra of fragments.Conclusions
Agreement between measurements and FLUKA results is encouraging and shows that FLUKA can predict microdosimetric spectra of mixed radiation fields created by therapeutic carbon ions in phantoms reasonably well.FLUKA simulations of the response of tissue-equivalent proportional counters to ion beams for applications in hadron therapy and space.
Physics in medicine and biology 56:20 (2011) 6545-6561
Abstract:
For both cancer therapy with protons and ions (hadron therapy) and space radiation environments, the spatial energy deposition patterns of the radiation fields are of importance for quantifying the resulting radiation damage in biological structures. Tissue-equivalent proportional counters (TEPC) are the principal instruments for measuring imparted energy on a microscopic scale and for characterizing energy deposition patterns of radiation. Moreover, the distribution of imparted energy can serve as a complementary quantity to particle fluences of the primary beam and secondary fragments for characterizing a radiation field on a physical basis for radiobiological models. In this work, the Monte Carlo particle transport code FLUKA is used for simulating energy depositions in TEPC by ion beams. The capability of FLUKA in predicting imparted energy and derived quantities, such as lineal energy, for microscopic volumes is evaluated by comparing it with a large set of TEPC measurements for different ion beams with atomic numbers ranging from 1 to 26 and energies from 80 up to 1000 MeV/n. The influence of different physics configurations in the simulation is also discussed. It is demonstrated that FLUKA can simulate energy deposition patterns of ions in TEPC cavities accurately and that it provides an adequate description of the main features of the spectra.Correction to 2010 83: 811-813 doi: 10.1259/bjr/49490647
British Journal of Radiology British Institute of Radiology 84:1001 (2011) 483-483
Benchmarking nuclear models of FLUKA and GEANT4 for carbon ion therapy.
Physics in medicine and biology 55:19 (2010) 5833-5847