Androgen deprivation and radiation therapy: sequencing studies using the Shionogi in vivo tumor system

Purpose: To test the relative effect of neoadjuvant and adjuvant androgen deprivation on the radiation response of an androgen dependent tumor. Methods and Materials: The transplantable, androgen dependent, Shionogi adenocarcinoma was grown as allografts in the hind limbs of NCr/Sed (nu/nu) athymic nude mice. Bilateral orchiectomy was the chosen form of androgen deprivation. Groups of tumors were irradiated to graded tumor doses and then studied for durable tumor control. The radiation response was expressed as the radiation dose required to control 50% of the tumors (TCD50). The sequence of radiation and orchiectomy was studied. Results: When radiation was combined with orchiectomy the Shionogi tumor was significantly more likely to be controlled than when radiation was used alone. Orchiectomy 12 days prior to radiation (neoadjuvant therapy) produced a significantly greater decline in the TCD50 than when orchiectomy was used 1 day or 12 days after radiation (adjuvant therapy). If, before radiation, tumors were allowed to regrow after orchiectomy to their original size in an androgen independent fashion then the advantage was largely lost. Those tumors responding well to neoadjuvant orchiectomy (>50% volume decrease) were significantly more likely to be eradicated by radiation than those with a lesser response. Conclusion: When using combinations of androgen deprivation and radiation in the treatment of the Shionogi tumor, sequence and timing of the therapies are crucial to maximize the effect