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Potentially Lethal Damage Repair and Sublethal Damage Repair After Proton Beam Irradiation: Comparison With X-ray Treatment
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Volume 96 Number 2S Supplement 2016 metastatic lesion. Changes in tumor size were measured for two (if possible) lesions located outside of the X-ray beams per patient: the largest lesion and if present, the smallest lesion among those 1cm. We measured the longest diameter of the lesions on CT images and evaluated the growth curves before, during, and after cDC-RT. Results: Among the 14 lesions evaluated, 3 lesions (21%) in 2 patients showed decrease in tumor size during the observation period. The other lesions continued to grow, and no abscopal effects were observed. The first case was a 66-year-old female with ovarian cancer. She underwent DCI for 11 months followed by concurrent RT using tomotherapy (55 Gy in 25 fractions) to liver metastases. Her enlarged right external iliac lymph node was evaluated; it kept growing until 11 months after RT but then turned to diminish. The second case was a 62-year-old female with colorectal cancer. She underwent DCI for 24 months and concurrent RT twice (39 Gy in 13 fractions and 50Gy in 4 fractions) to lung metastases at intervals. Other lung metastatic lesions were measured; both of them followed the same course as that of the first case, i.e., growth during 11 months and subsequent shrinkage. Conclusion: We experienced tumor shrinkage outside the RT fields in patients treated with cDC-RT. The treatment may produce abscopal effects in a proportion of patients. There seems to be an interval of up to 1 year after RT before the effects become evident. Further investigation appears to be warranted. Author Disclosure: K. Nakajima: None. Y. Shibamoto: None. M. Kobayashi: None. T. Takaoka: None. T. Murai: None. Y. Manabe: None. C. Sugie: None. T. Yanagi: None.
3399 Comparison of the Biology Optimization and Physical Optimization for Cervical Carcinoma Z. Feng,1 C. Tao,2 G. Yu,1 S. Qin,1 J. Zhu,2 C. Ma,2 Y. Yin,2 and D. Li1; 1 Shandong Province Key Laboratory of Medical Physics and Image Processing Technology, School of Physics and Electronics, Shandong Normal University, Jinan, China, 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China Purpose/Objective(s): Intensity modulated radiation therapy (IMRT) is the most used radiation planning technique for cervical carcinoma. In common commercial treatment planning systems, physical parameters are used for IMRT optimization. However, these physical parameters didn’t consider the biological effects. In this work, we applied the biologically based IMRT optimization model in the clinical environment for cervical carcinoma cases and evaluated the results with the physical optimization. Materials/Methods: Twenty patients of advanced stage cervical carcinoma were selected for this study. IMRT plans with biological optimization were compared to their corresponding plans with physical optimization. Plan evaluation was performed using both physical parameters and biological parameters. Results: The target coverage and conformity were very similar between the 2 optimization, and there were no significant differences in the tumor control probability (TCP) values between the 2 optimizations. The volume of bladder and rectum received doses of above 40 Gy were comparable, and there were no significant differences between these two optimizations. The same situation was observed in mean dose of bladder and rectum. The normal tissue complication probability (NTCP) of bladder and rectum produced by biological optimization were 0.144 and 0.108, respectively, while those of physical optimization were 0.178 and 0.186, respectively, and there were significant differences in the NTCP values between the two optimizations. Conclusion: Our results showed that applying the biological optimization in IMRT did not decrease the plan quality for cervical carcinoma. The
biological optimization could be a potential alternative method to the physical optimization. Author Disclosure: Z. Feng: None. C. Tao: None. G. Yu: None. S. Qin: None. J. Zhu: None. C. Ma: None. Y. Yin: None. D. Li: None.
3400 Potentially Lethal Damage Repair and Sublethal Damage Repair After Proton Beam Irradiation: Comparison With X-ray Treatment S. Hashimoto,1,2 C. Sugie,2 H. Iwata,1 H. Ogino,1 C. Omachi,3 K. Yasui,4 J.E. Mizoe,1,2 and Y. Shibamoto2; 1Department of Radiation Oncology, Nagoya Proton Therapy Center, Nagoya, Japan, 2Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, 3Department of Proton Therapy Physics, Nagoya Proton Therapy Center, Nagoya, Japan, 4Department of Proton Therapy Technology, Nagoya Proton Therapy Center, Nagoya, Japan Purpose/Objective(s): After irradiation, potentially lethal damages can be repaired depending on the conditions of environments around the cells. Sublethal damage can be repaired in hours unless additional sublethal damage occurs. In order to clarify the biological response of tumor cells to proton beam irradiation, potentially lethal damage repair (PLDR) and sublethal damage repair (SLDR) after proton beam irradiation were investigated in comparison with those after X-irradiation. Materials/Methods: EMT6 mouse sarcoma cells and HSG human salivary gland neoplastic cells were used in this study. Irradiation was carried out using 210-kVp X-rays at a dose rate of 1.0 Gy/min and using 225-MeV proton beams at a dose rate of 1.0 GyE/min. We used a relative biological effectiveness value of 1.1 according to our previous investigation. In Experiment 1 to investigate the extent of PLDR, a delayed plating assay was conducted with the cells in exponential growth phase (EGP) cultures and plateau phase (PP) cultures. For EGP cultures, the cells were grown sparsely with adequate nutrition, while in confluent PP cultures the cell number per dish did not show further increase. The cells were plated in plastic dishes for colony assay immediately or 0.5-24 h after irradiation at 8 Gy/GyE with proton beams or X-rays. In Experiment 2 to investigate the extent of SLDR, a total dose of 8 Gy/GyE was given to the EGP cells in two fractions with an interfraction interval of 0.5e6 h, or without interruption. In Experiment 3 to investigate SLDR during fractionated irradiation, a total dose of 8 GyE was given to the EGP cells in 5 fractions of 1.6 GyE each with interfraction intervals of 1e5 min each, or without interruption. In Experiment 3, the data were compared those previously obtained for X-rays. In all experiments, the standard colony assay was used to determine cell survival. Assays were repeated 3 times for each experiment. Results: In Experiment 1, apparent PLDR was observed in EMT6 cells for both X-rays and proton beams; the PLDR appeared to reach a plateau within 2 h, and the surviving fractions of the PP cells were significantly higher than for those of the EGP cells. While apparent PLDR was observed after X-irradiation in PP HSG cells, PLDR after proton beam irradiation was much lower. In Experiment 2, apparent SLDR was observed with X-irradiation to EMT6 and HSG cells, and it appeared to reach a plateau within 2 h. On the other hand, SLDR was remarkably suppressed after proton irradiation in EMT6 and HSG cells. In Experiment 3, SLDR also appeared to take place to a lesser extent during proton irradiation in EMT6 cells, compared to X-irradiation. The differences were significant when the interval was 3 min or longer. However, SLDR in HSG cells was not significant with any interval after proton irradiation. Conclusion: Compared to X-irradiation, PLDR and SLDR may take place to a lesser extent after proton beam irradiation. Author Disclosure: S. Hashimoto: None. C. Sugie: None. H. Iwata: None. H. Ogino: None. C. Omachi: None. K. Yasui: None. J. Mizoe: None. Y. Shibamoto: None.
Volume 96 Number 2S Supplement 2016 metastatic lesion. Changes in tumor size were measured for two (if possible) lesions located outside of the X-ray beams per patient: the largest lesion and if present, the smallest lesion among those 1cm. We measured the longest diameter of the lesions on CT images and evaluated the growth curves before, during, and after cDC-RT. Results: Among the 14 lesions evaluated, 3 lesions (21%) in 2 patients showed decrease in tumor size during the observation period. The other lesions continued to grow, and no abscopal effects were observed. The first case was a 66-year-old female with ovarian cancer. She underwent DCI for 11 months followed by concurrent RT using tomotherapy (55 Gy in 25 fractions) to liver metastases. Her enlarged right external iliac lymph node was evaluated; it kept growing until 11 months after RT but then turned to diminish. The second case was a 62-year-old female with colorectal cancer. She underwent DCI for 24 months and concurrent RT twice (39 Gy in 13 fractions and 50Gy in 4 fractions) to lung metastases at intervals. Other lung metastatic lesions were measured; both of them followed the same course as that of the first case, i.e., growth during 11 months and subsequent shrinkage. Conclusion: We experienced tumor shrinkage outside the RT fields in patients treated with cDC-RT. The treatment may produce abscopal effects in a proportion of patients. There seems to be an interval of up to 1 year after RT before the effects become evident. Further investigation appears to be warranted. Author Disclosure: K. Nakajima: None. Y. Shibamoto: None. M. Kobayashi: None. T. Takaoka: None. T. Murai: None. Y. Manabe: None. C. Sugie: None. T. Yanagi: None.
3399 Comparison of the Biology Optimization and Physical Optimization for Cervical Carcinoma Z. Feng,1 C. Tao,2 G. Yu,1 S. Qin,1 J. Zhu,2 C. Ma,2 Y. Yin,2 and D. Li1; 1 Shandong Province Key Laboratory of Medical Physics and Image Processing Technology, School of Physics and Electronics, Shandong Normal University, Jinan, China, 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China Purpose/Objective(s): Intensity modulated radiation therapy (IMRT) is the most used radiation planning technique for cervical carcinoma. In common commercial treatment planning systems, physical parameters are used for IMRT optimization. However, these physical parameters didn’t consider the biological effects. In this work, we applied the biologically based IMRT optimization model in the clinical environment for cervical carcinoma cases and evaluated the results with the physical optimization. Materials/Methods: Twenty patients of advanced stage cervical carcinoma were selected for this study. IMRT plans with biological optimization were compared to their corresponding plans with physical optimization. Plan evaluation was performed using both physical parameters and biological parameters. Results: The target coverage and conformity were very similar between the 2 optimization, and there were no significant differences in the tumor control probability (TCP) values between the 2 optimizations. The volume of bladder and rectum received doses of above 40 Gy were comparable, and there were no significant differences between these two optimizations. The same situation was observed in mean dose of bladder and rectum. The normal tissue complication probability (NTCP) of bladder and rectum produced by biological optimization were 0.144 and 0.108, respectively, while those of physical optimization were 0.178 and 0.186, respectively, and there were significant differences in the NTCP values between the two optimizations. Conclusion: Our results showed that applying the biological optimization in IMRT did not decrease the plan quality for cervical carcinoma. The
biological optimization could be a potential alternative method to the physical optimization. Author Disclosure: Z. Feng: None. C. Tao: None. G. Yu: None. S. Qin: None. J. Zhu: None. C. Ma: None. Y. Yin: None. D. Li: None.
3400 Potentially Lethal Damage Repair and Sublethal Damage Repair After Proton Beam Irradiation: Comparison With X-ray Treatment S. Hashimoto,1,2 C. Sugie,2 H. Iwata,1 H. Ogino,1 C. Omachi,3 K. Yasui,4 J.E. Mizoe,1,2 and Y. Shibamoto2; 1Department of Radiation Oncology, Nagoya Proton Therapy Center, Nagoya, Japan, 2Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, 3Department of Proton Therapy Physics, Nagoya Proton Therapy Center, Nagoya, Japan, 4Department of Proton Therapy Technology, Nagoya Proton Therapy Center, Nagoya, Japan Purpose/Objective(s): After irradiation, potentially lethal damages can be repaired depending on the conditions of environments around the cells. Sublethal damage can be repaired in hours unless additional sublethal damage occurs. In order to clarify the biological response of tumor cells to proton beam irradiation, potentially lethal damage repair (PLDR) and sublethal damage repair (SLDR) after proton beam irradiation were investigated in comparison with those after X-irradiation. Materials/Methods: EMT6 mouse sarcoma cells and HSG human salivary gland neoplastic cells were used in this study. Irradiation was carried out using 210-kVp X-rays at a dose rate of 1.0 Gy/min and using 225-MeV proton beams at a dose rate of 1.0 GyE/min. We used a relative biological effectiveness value of 1.1 according to our previous investigation. In Experiment 1 to investigate the extent of PLDR, a delayed plating assay was conducted with the cells in exponential growth phase (EGP) cultures and plateau phase (PP) cultures. For EGP cultures, the cells were grown sparsely with adequate nutrition, while in confluent PP cultures the cell number per dish did not show further increase. The cells were plated in plastic dishes for colony assay immediately or 0.5-24 h after irradiation at 8 Gy/GyE with proton beams or X-rays. In Experiment 2 to investigate the extent of SLDR, a total dose of 8 Gy/GyE was given to the EGP cells in two fractions with an interfraction interval of 0.5e6 h, or without interruption. In Experiment 3 to investigate SLDR during fractionated irradiation, a total dose of 8 GyE was given to the EGP cells in 5 fractions of 1.6 GyE each with interfraction intervals of 1e5 min each, or without interruption. In Experiment 3, the data were compared those previously obtained for X-rays. In all experiments, the standard colony assay was used to determine cell survival. Assays were repeated 3 times for each experiment. Results: In Experiment 1, apparent PLDR was observed in EMT6 cells for both X-rays and proton beams; the PLDR appeared to reach a plateau within 2 h, and the surviving fractions of the PP cells were significantly higher than for those of the EGP cells. While apparent PLDR was observed after X-irradiation in PP HSG cells, PLDR after proton beam irradiation was much lower. In Experiment 2, apparent SLDR was observed with X-irradiation to EMT6 and HSG cells, and it appeared to reach a plateau within 2 h. On the other hand, SLDR was remarkably suppressed after proton irradiation in EMT6 and HSG cells. In Experiment 3, SLDR also appeared to take place to a lesser extent during proton irradiation in EMT6 cells, compared to X-irradiation. The differences were significant when the interval was 3 min or longer. However, SLDR in HSG cells was not significant with any interval after proton irradiation. Conclusion: Compared to X-irradiation, PLDR and SLDR may take place to a lesser extent after proton beam irradiation. Author Disclosure: S. Hashimoto: None. C. Sugie: None. H. Iwata: None. H. Ogino: None. C. Omachi: None. K. Yasui: None. J. Mizoe: None. Y. Shibamoto: None.