4.CLINICAL RESEARCH

  1. Dose-volume Histogram Analysis of High Dose Rate Intracavitary Brachytherapy for Uterine Cervix Cancer
  2. Correlation Between c-erbB-2 Oncogene and Cell Proliferation Parameters in Radiation Therapy for Cervical Cancer.
  3. MnĦSOD Expression Correlates with p53 Status and Local Recurrence of Cervical Carcinoma Treated with Radiation Therapy



a Higher Contents

1.Dose-volume Histogram Analysis of High Dose Rate Intracavitary Brachytherapy for Uterine Cervix Cancer

Atsuro Terahara, Takashi Nakano, Atsuko Ishikawa, Shinroku Morita, Hirohiko Tsujii, and Yuzuru Nakamura

Keywords: uterine cervix cancer, dose-volume histogram, brachytherapy


@We retrospectively analyzed the relationship between dose distribution and local control using a dose-volume histogram (DVH) in patients with cancer of the uterine cervix treated by definitive radiotherapy including intracavitary brachytherapy. @Twenty-five patients with squamous cell carcinoma of the uterine cervix who underwent definitive radiotherapy between August 1987 and April 1994 were selected for the present study. They included 15 patients with local control and 10 patients with local recurrence. In principle, these patients were treated with 50 Gy of external beam pelvic radiotherapy and a point A dose of 24 Gy, in four fractions, of intracavitary brachytherapy. The DVHs of tumor volumes were calculated by superimposing three-dimensional dose distributions on computed tomography (CT) images taken before brachytherapy (Fig. 1). @Differential DVHs revealed a tendency for the portion of the total tumor volume to which the delivered dose was low to be larger in patients with local recurrence. The tumor volumes and the absolute dose volumes of which the absorbed dose was less than 24 Gy [DV (ƒ 24 Gy)] were significantly larger in patients with local recurrence than those in local control patients (p  0.02 and 0.03, respectively). The actuarial local control rate of patients whose absolute DV (ƒ 24 Gy) was more than 50 Ħ was significantly lower than that of patients with absolute DV (ƒ 24 Gy) of 50 Ħ or less (p  0.02). The percent DV (ƒ 24 Gy) was not significantly different in the two groups. In patients with larger tumor volume, the absolute DV (ƒ 24 Gy) was also larger and a strong linear correlation was noted between them. The analysis of dose distribution of brachytherapy using DVH was useful to evaluate the quality of dose distribution quantitatively. The absolute dose volume was considered more important than the percent dose volume for evaluation of the clinical outcome. Our study suggested that unfavorable dose distribution for the tumor volume in brachytherapy was one of the reasons for poor local control in patients with large tumor volume.
[Publications]
Terahara, A., Nakano, T., Ishikawa, A., Morita, S., Tsuji, H.: Int. J. Radiat. Oncol. Biol. Phys. 35, 549-54, 1996.


Fig.1 Differential DVH by local control (absolute volume). (a) Absolute version of differential DVH of patients with local control (n15). Most patients in this group had a small tumor volume for which irradiation dose was relatively low.(b) Absolute version of differential DVH of patients with local recurrence (n10). There was a trend that the portions of the tumors receiving lower dose were relatively large compared with (a). 

a Higher Contents
Contents
Next
a Higher Next

2.Correlation Between c-erbB-2 Oncogene and Cell Proliferation Parameters in Radiation Therapy for Cervical Cancer.

Takashi Nakano,Kuniyuki Oka,Atsuko Ishikawa, and Shinroku Morita.

Keywords : CerbB2, Ki-67, cervical cancer, radiation therapy, growth fraction


Background. Although c-erbB-2 oncoprotein expression (CerbB-OPE) is regarded as being associated with tumor cell proliferation and prognosis, the correlation between CerbB-OPE and cell proliferation parameters has not been fully analyzed. Methods. Immunohistochemical study was performed on 64 cervical cancer patients treated with radiation therapy. Prognosis was analyzed by CerbB-OPE, growth fraction determined with Ki-67 immunohistochemistry (Ki-GF) and the mitotic index of proliferating cell population (pMI). Results. CerbB-OPE was observed on the cell membrane of cancer cells. Positivity of CerbB-OPE, which was 42.4“ in total,increased significantly with stage progression. No significant differences were observed between histologic subtypes. Mean Ki-GF and pMI were 36“ and 2.5“ in total, respectively.Mean Ki-GF for CerbB({) patients was 26.2“, significantly lower than the 38.3“ for CerbB(Ħ) patients (pƒ0.01). The mean pMI for CerbB({) patients was 3.70“, significantly higher than the 2.00“ of CerbB(Ħ) patients (pƒ0.05). The 5-year survival rates of CerbB({) and CerbB(Ħ) patients were 45.1“ and 75.6“. respectively, indicating that CerbB ({) patients showed significantly poorer survival than CarbB(Ħ) ones(Pƒ0.01). The difference in survival was mainly due to local recurrence rather than distant metastasis. There were significant correlations between prognosis and KiĦGF and pMI. Conclusions. The poor prognosis of the cervical cancer with CerbBĦOPE was due to local recurrence following radiation therapy. The correlations between CerbBĦOPE and KiĦGF and pMI suggest that cĦerbBĦ2 oncoprotein may play an important role in cell proliferation status of cancer of the uterine cervix.
[Publications]
1)Nakano, T., Oka, K., Ishikawa, A., and Morita, S.: Cancer, 79, 513520, 1997.
2)Nakano, T., Oka, K., and Taniguch, Y.: Cancer Res., 56, 2771Ħ2775, 1996.
3)Oka, K. Nakano, T., and Hoshi, T.: Cancer, 77, 2280Ħ2285, 1996

a Higher Contents
Contents
Next
a Higher Next

3.MnĦSOD Expression Correlates with p53 Status and Local Recurrence of Cervical Carcinoma Treated with Radiation Therapy

Takashi Nakano, Kuniyuki Oka, Atsuko Ishikawa, Shinroku Morita and Hirohiko Tsujii

Keywords: MnĦSOD, p53, Radiation therapy, Cervical cancer, prognosis


Background. Manganese superoxide dismutase (MnĦSOD) inactivates the radiation effect by removal of the radiation induced toxic superoxide radicals. The purpose of this study is to assess the correlation between MnĦSOD, radiation sensitivity and prognosis following radiation therapy. Methods. The MnĦSOD, p53 protein, and cĦerbB2 oncoprotein expressions in 52 specimens from patients with cervical cancer treated with radiation therapy were investigated immunohistochemically. The frozen sections were stained using anti human MnĦSOD, and anti p53 monoclonal antibodies, and anti cĦerbBĦ2 oncoprotein polyclonal antibody, following avidine biotine peroxidase complex methods. Correlations between the MnĦSOD expression and prognosis or failure patterns were analyzed. Additionally, correlations between p53 and cĦerbBĦ2 oncoproteins and MnĦSOD expression were investigated. Results. Positive expression of MnĦSOD in cervical cancer was 48.1“. No significant difference in positivity of MnĦSOD expression was noted according to stage and histologic subtypes. The 5Ħyear survival rate of MnĦSOD positive patients was 42.5“, significantly poorer than the 77.0“ of MnĦSOD negative patients (pƒ0.05). Fig.1 Analyzing the failure patterns, patients with MnĦSOD expression showed a significantly higher incidence of local recurrence than those without. However, there was no difference in distant matastasis between them. Although both p53 and cĦerbBĦ2 oncoprotein expressions were significantly associated with the prognosis of the same patients, MnĦSOD expression was associated with p53 oncoprotein expression but was not with that of cĦerbBĦ2 oncoprotein. Conclusions. Our results demonstrate that the MnĦSOD level of cancer cells is correlated with local control and is an important prognostic factor in radiation therapy for cervical cancer. MnĦSOD level may help explain the intrinsic radiation sensitivity of cervical cancer cells.
[Publications]
1)Nakano, T., Oka, K, and Taniguch, Y.: Cancer Res., 56. 2771Ħ2775, 1996.
2)Oka, K., Nakano, T., and Hoshi, T.: Cancer, 77, 2280Ħ2285, 1996.

a Higher Contents
Contents
a Higher Next