Neutron or photon irradiation for prostate tumors: Enhancement of cytokine therapy in a metastatic tumor model

G. G. Hillman, R. L. Maughan, D. J. Grignon, M. Yudelev, J. Rubio, S. Tekyi-Mensah, A. Layer, M. Che, J. D. Forman

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Abstract

We have shown that implantation of human prostate carcinoma PC-3 cells in the prostates of nude mice led to the formation of prostate tumors with metastases to para-aortic lymph nodes. We found that day 6 prostate tumors were responsive to systemic injections of interleukin 2 (IL-2) therapy. We have now investigated the combination of primary tumor irradiation and IL-2 for metastatic prostate cancer in this preclinical tumor model. The effect of neutron radiation was compared with that of photon radiation. Advanced prostate tumors (∼0.4 cm) were irradiated, and a day later, mice were treated with systemic IL-2 for three weekly cycles. In separate experiments, mice were either sacrificed on day 30 to assess prostate tumor size and tumor histology or followed for survival. A dose-dependent inhibition of prostate tumor growth was caused either by photons or neutrons, but neutrons were more effective than photons with a relative biological effectiveness of 2. The tumor inhibition obtained with 250 cGy neutrons and 500 cGy photons was significant (>75%) and was further increased (≥90%) by addition of IL-2 therapy. In survival studies, the combination of radiation and IL-2 showed a significant survival advantage compared with untreated mice (P ≤ 0.005) or radiation alone (P ≤ 0.003) and an increase in median survival compared with IL-2 alone. Histologically, the combined regimen resulted in a greater degree of tumor destruction, inflammatory response, and vascular damage than that observed with each modality alone. After this combined treatment, no tumor was histologically detected in the para-aortic lymph nodes of these mice, and the lymph nodes were significantly smaller. These findings showed that primary tumor irradiation, either with neutrons or photons, enhanced IL-2 therapeutic effect for the treatment of advanced prostate cancer. This combined modality induced an antitumor response that controlled the growth of prostate tumors and their metastases.

Original languageEnglish (US)
Pages (from-to)136-144
Number of pages9
JournalClinical Cancer Research
Volume7
Issue number1
StatePublished - Feb 12 2001

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Hillman, G. G., Maughan, R. L., Grignon, D. J., Yudelev, M., Rubio, J., Tekyi-Mensah, S., Layer, A., Che, M., & Forman, J. D. (2001). Neutron or photon irradiation for prostate tumors: Enhancement of cytokine therapy in a metastatic tumor model. Clinical Cancer Research, 7(1), 136-144.