gms | German Medical Science

48th Meeting of the Particle Therapy Co-Operative Group

Particle Therapy Co-Operative Group (PTCOG)

28.09. - 03.10.2009, Heidelberg

Prognostic Impact of Mitotic Index Of Proliferating Cell Populations (pMI) in Cervical Cancer Patients Treated with Carbon Ion Beam

Meeting Abstract

  • Y. Suzuki - Gunma University Graduate School of Medicine, Maebashi, Japan
  • K. Oka - Mito Saiseikai General Hospital, Mito, Japan
  • T. Ohno - Gunma University Graduate School of Medicine, Maebashi, Japan
  • S. Kato - Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan
  • H. Tsujii - Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan
  • T. Nakano - Gunma University Graduate School of Medicine, Maebashi, Japan

PTCOG 48. Meeting of the Particle Therapy Co-Operative Group. Heidelberg, 28.09.-03.10.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. Doc09ptcog196

DOI: 10.3205/09ptcog196, URN: urn:nbn:de:0183-09ptcog1965

Published: September 24, 2009

© 2009 Suzuki et al.
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Outline

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Purpose: We previously reported that the Mitotic Index of a Proliferating Cell Population (pMI) was a potent prognostic factor in cervical cancer patients treated with photon beam therapy (Nakano T and Oka K. Cancer. 1993.15;72(8):2401-8.). In this study, we investigated whether the pMI accurately predicted prognosis in cervical cancer patients treated with carbon ion beam.

Methods and materials: Tissue sections were obtained from 27 consecutively treated patients with stage IIIB bulky (19 patients) and IVA (8 patients) squamous cell carcinomas of the cervix treated with carbon ion beam at the National Institute of Radiological Sciences, Japan , as a phase I&II study with dose escalation methodology (52.8-72GyE/24fraction). All patients were followed for a minimum of 5 years or until death. Tissue sections were obtained from all 27 patients before treatment. They were excised from the cervical tumors and fixed in 10% formaldehyde for approximately 24 hours and embedded in paraffin. The Mitotic Index (MI) and Ki-67 labeling index (Ki-67-LI) were determined by hematoxylin and eosin staining and immunohistochemical staining, respectively. The pMI was calculated using the following formula; (pMI)=(MI)/(Ki-67-LI).

Results: The pMI ranged from 0.6 to 8.9 (mean and median: 3.9+2.6 and 3.2). Twelve of the 27 specimens had a pMI greater than 3.5. The local control rate in tumors with a pMI of greater than 3.5 was 17%, significantly lower than the 73% in the tumors with a pMI of less than 3.5 (p=0.005). The local control rate of the tumors with a greater than 1.5% MI was 17%, significantly lower than the 66% of the tumors with less than 1.5% pMI (p=0.02). The local control rate of the tumors with a Ki-67-LI of greater than 33% was 64%, which was higher than the 37% of the tumors with a Ki-67-LI of less than 33% , although the difference was not significant (p=0.13). Multivariate analysis indicated that the pMI had the strongest impact on local control (standard regression coefficient=0.48, p=0.002) among the variables, including clinical stage, irradiated dose, age and tumor volume. The metastasis-free survival rate of the tumors with greater than 3.5 pMI was 23%, lower than the 58% of the tumors with less than 3.5 pMI, although the difference was not significant (p=0.26).

Conclusions: These results suggest that a high pMI is an indication of a poorer prognosis, and is a powerful prognostic factor for local control in patients with squamous cell carcinomas of the cervix treated with carbon ion beam therapy. Altough further studies with larger datasets is warranted, to improve the local control rate of CIRT for cervical squamous cell carcinoma, especially for those tumors having a high pMI, a hypofractionated short-treatment-time regimen and together with the use of chemotherapy should be further explored.