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65. Clinico-pathological and Molecular Biological Analysis of Heavy Ion Radiation Effect
Takashi Nakano., Yoshiyuki Suzuki., Tatsuya Ohono., Michiya Suzuki., Atsuko Abe., Shinroku Morita., Shinichiro Sato., and Shigeru Yamada.,Nobuyuki Miyahara., Hirohiko Tsujii., Hideo Niibe*
(*Gunma University)
Keywords: carbon beam therapy, cervical cancer, pO2
Objective: High-LET particles are believed to decrease radiation resistance of tumors originating from hypoxia and different radiation sensitivity in the cell cycle. However, no proof of the effect has been provided by clinical trial and related clinical research. Hence, we investigated the radiation biological aspect of the high-LET carbon beam therapy on cervical cancer.
Materials and Methods: This study involved 27 patients with stage 3B and 4A squamous cell carcinomas of the cervix treated with high-LET carbon beams and, as control, 28 patients of the same disease treated with conventional photon beams between 1995 and 1998. The pO2 was measured by using a needle-type polarographic oxygen electrode and cell proliferation parameters were obtained with immunohistochemical staining.
Results: The cumulative survival rate and local control rate of 27 patients with advanced squamous cell carcinoma indicated the 3-year survival rate of 66.3 % and local control rate of 65 %. Of these, 23 patients were examined for tumor pO2 status. The mean and median pO2 of tumors before treatment were 16.5±9.0 mmHg and 13.7 mHg which were significantly increased to 24.4±9.7 mmHg and 25.2 mmHg, at The 5th Day, respectively (p=0.002). The numbers of patients with pO2 =< 20 mmHg and > 20 mm Hg before treatment were 14 and 9, respectively. The 3-year local control rate of patients with pO2 =< 20 mmHg and > 20 mmHg were 38 % and 44 %, respectively, which was not a significant difference (p=0.66). The local control rates of the pO2 =< 20 mmHg and > 20 mmHg before treatment were 64.3% and 66.7 %, respectively, which were almost the same between them and not significantly different. The numbers of patients with pO2 =< 20 mmHg and > 20 mmHg at The 5th Day were 8 and 15, respectively. The survival rates of the pO2 =< 20 mmHg and > 20 mmHg at The 5th Day were 33 % and 51%, respectively, which was not a significant difference. (p=0.20). The local control rates of pO2 =< 20 mmHg and > 20 mmHg at The 5th Day were 50.0 % and 73.3 %, respectively, which was not a significant difference. Recurrence did not correlate with tumor volume. Mitotic index of proliferating cell population of tumor (pMI) is considered to represent cell cycle speed of tumor. The 3 year local control rate of pMI=< 4% was 78.6 %, which was significantly poorer than the 38.5 % of pMI > 4%.
Conclusion: The increases in both pO2 at The 5th Day and the number of oxygenated tumors indicated that the reoxygenation phenomenon occurred within 1 week after initiation of carbon beam therapy, the same as with photon beam therapy. The similar survival and local control rates for oxygenated tumors and hypoxic tumors before treatment indicated that tumor oxygenation status had not so important a role in local control in carbon beam therapy. Tumors of high pMI or rapidly proliferating tumors developed significant recurrence. These results indicated that high-LET beam irradiation may overcome radiation resistant nature of anoxic tumors, but it can not overcome tumors with faster cell cycle speed.
