Christin Glowa1, Christian P Karger2, Stephan Brons3, Dawen Zhao4, Ralph P Mason4, Peter E Huber5, Jürgen Debus6, Peter Peschke7. 1. Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany; Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany. Electronic address: c.glowa@dkfz.de. 2. Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany. 3. National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany; Heidelberg Ion Beam Therapy Center (HIT), Heidelberg, Germany. 4. Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 5. Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany; National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany; Department of Molecular Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 6. Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany; National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany. 7. National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany; Department of Molecular Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Abstract
OBJECTIVE: To quantitatively study the impact of intrinsic tumor characteristics and microenvironmental factors on local tumor control after irradiation with carbon ((12)C-) ions and photons in an experimental prostate tumor model. MATERIAL AND METHODS: Three sublines of a syngeneic rat prostate tumor (R3327) differing in grading (highly (-H) moderately (-HI) or anaplastic (-AT1)) were irradiated with increasing single doses of either (12)C-ions or 6 MV photons in Copenhagen rats. Primary endpoint was local tumor control within 300 days. The relative biological effectiveness (RBE) of (12)C-ions was calculated from the dose at 50% tumor control probability (TCD50) of photons and (12)C-ions and was correlated with histological, physiological and genetic tumor parameters. RESULTS: Experimental findings demonstrated that (i) TCD50-values between the three tumor sublines differed less for (12)C-ions (23.6-32.9 Gy) than for photons (38.2-75.7 Gy), (ii) the slope of the dose-response curve for each tumor line was steeper for (12)C-ions than for photons, and (iii) the RBE increased with tumor grading from 1.62 ± 0.11 (H) to 2.08 ± 0.13 (HI) to 2.30 ± 0.08 (AT1). CONCLUSION: The response to (12)C-ions is less dependent on resistance factors as well as on heterogeneity between and within tumor sublines as compared to photons. A clear correlation between decreasing differentiation status and increasing RBE was found. (12)C-ions may therefore be a therapeutic option especially in patients with undifferentiated prostate tumors, expressing high resistance against photons.
OBJECTIVE: To quantitatively study the impact of intrinsic tumor characteristics and microenvironmental factors on local tumor control after irradiation with carbon ((12)C-) ions and photons in an experimental prostate tumor model. MATERIAL AND METHODS: Three sublines of a syngeneic ratprostate tumor (R3327) differing in grading (highly (-H) moderately (-HI) or anaplastic (-AT1)) were irradiated with increasing single doses of either (12)C-ions or 6 MV photons in Copenhagen rats. Primary endpoint was local tumor control within 300 days. The relative biological effectiveness (RBE) of (12)C-ions was calculated from the dose at 50% tumor control probability (TCD50) of photons and (12)C-ions and was correlated with histological, physiological and genetic tumor parameters. RESULTS: Experimental findings demonstrated that (i) TCD50-values between the three tumor sublines differed less for (12)C-ions (23.6-32.9 Gy) than for photons (38.2-75.7 Gy), (ii) the slope of the dose-response curve for each tumor line was steeper for (12)C-ions than for photons, and (iii) the RBE increased with tumor grading from 1.62 ± 0.11 (H) to 2.08 ± 0.13 (HI) to 2.30 ± 0.08 (AT1). CONCLUSION: The response to (12)C-ions is less dependent on resistance factors as well as on heterogeneity between and within tumor sublines as compared to photons. A clear correlation between decreasing differentiation status and increasing RBE was found. (12)C-ions may therefore be a therapeutic option especially in patients with undifferentiated prostate tumors, expressing high resistance against photons.
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