Dr. G. Peter Raaphorst

Research Summary

The study of radiosensitization of human cancer cells to radiation using hyperthermia and drugs. This project includes the study of the response of a wide range of human tumour cells (glioma, ovarian carcinoma, breast cancer, melanoma etc) to radiation at different dose rates and the effect of hyperthermia (heating from 40 to 45oC) on radiosensitization. In addition the effect of chemotherapy agents in combination with hyperthermia and radiation is also being evaluated. In these studies we are also assessing the mechanisms of radiation resistance and the capacity of cells to repair radiation damage. The experimental results are being modelled in order to develop comprehensive models that can be used to predict radiotherapy outcome. These studies also include design of special radiation apparatus to deliver specific dose rates and require the development of a good understanding of radiation dosimetry.

Prediction of radiation response. In this study we are evaluating the response of human normal and tumour cells in culture to irradiation. The normal and tumour cells are obtained from patients before undergoing radiation therapy and are assessed for the radiation response and then compared to the response of the patient undergoing radiotherapy. To date we have found a correlation between the in-vitro and the patient tissue response. Further studies are ongoing to model these responses and to determine whether the results can be used as a predictor of radiation sensitivity and for customised dose prescription in order to optimise radiotherapy.

# Induction of radiation resistance with low doses of radiation. Our preliminary studies have shown that low dose and low dose rate irradiation can induce radiation resistance in human cells. This can have a major impact on radiation therapy where in some cases radiation is given either in fractions or at low dose rate. In addition such resistance can also have an impact on working in low level radiation fields such as those found in some industries or in outer space. We are currently characterising this induced resistance in human cells and will develop strategies for its optimization. In addition, we are also looking at other means to induce or possibly prevent induction of radiation resistance. These results are being put into models to help predict the radiotherapy response.

Publications/Presentations

1. M. Carlone, D. Wilkins and G.P. Raaphorst, "The modified linear quadratic model of Guerrero and Li can be derived from a mechanistic basis and exhibits -linear-quadratic-linear behavior", Physics in Medicine and Biology, 21, 4825-35 (2005).
2. G.P. Raaphorst, L.F. Li, D.P. Yang and J.M. Leblanc, "Cisplatin sensitization by concurrent mild hyperthermia in parental and mutant cell lines deficient in homologous recombination and nonhomologous endjoining repair", Oncology Reports. 14, 281-5 (2005).
3. G.P. Raaphorst and D.P. Yang, "Evaluation of thermal cisplatin sensitization in normal and XP human cells using mild hyperthermia at 40 and 41oC, Anticancer Res. 25,2649-53, (2005).
4. M. Carlone, D. Wilkins, G.P. Raaphorst. "In Regard to D'Souza et al. (Int. J. Radiat. Oncol. Biol Phys 2004 58:1540-1548). Dose volume conundrum for response of prostate cancer to brachytherapy: summary of dosimetric measures and their relationship to tumor control probability", Int. J. Radiat. Oncol. Biol. Phys, 62, 298-9, (2005).
5. G.P. Raaphorst, J-Maude Leblanc, D.P. Yang, L.F. Li, "Comparison of response to cisplatin, radiation and combined treatment in cell lines deficient in recombinational repair", Anti Cancer Res., 25, 53-58 (2005).
6. G.P. Raaphorst and J-Maude Leblanc, "Evaluation of thermal cisplatin sensitization in chicken DT40 cells normal and deficient in DNA homologous and nonhomologous endjoining repair", Letters in Drug Design & Discovery, 2, 55-61 (2005).
7. J-Maude Leblanc and G.P. Raaphorst, "The evaluation of cisplatin treatment given concurrently with pulsed irradiation treatment in cisplatin sensitive and resistant human ovarian carcinoma cell lines". Int. J. Radiat. Biol , 81,29 - 435 (2005).
8. M. Carlone, D. Wilkins, B. Nyiri and G.P. Raaphorst, "TCP isoeffect analysis using a heterogeneous distribution of radiosensitivity", Medical Physics 31, (5), 1176-82 (2004).
9. G.P. Raaphorst, D.P. Yang and M. Niedbala, "Is DNA polymerase beta important in thermal radiosensitization?", Int. J. Hyperthermia¡¨, 20, 140-143 (2004).
10. M. Carlone, D. Wilkins and G.P. Raaphorst, "Radiobiological parameter estimation for a predictive tumour control model for early stage prostate carcinoma", Polish Journal of Medical Physics and Engineering, 9, 931-945 (2004).
11. G.P. Raaphorst, D.P. Yang and L. Li, "Comparison of human tumour cell responses to cisplatin and ZD0473 with and without irradiation", Anti Cancer Research, 24, 613-618 (2004).
12. G.P. Raaphorst, J-M. Leblanc and L. Li, "Evaluation of recombination repair pathways in thermal radiosensitization", Radiat. Res., 161, 215-218 (2004).
13. E.P. Armour and G.P. Raaphorst, "Long duration mild hyperthermia in brachytherapy", Int. J. Hyperthermia 20, 175- 189 (2004).