Radiation dose response for subclinical metastases

The development of adjuvant therapies for subclinical metastases has been empiric. Decades of experience showed that 45 to 50 Gy resulted in high control rates for subclinical lymph node involvement. By analogy with the response of macroscopic tumors, in which doses below a threshold yield no benefit, it was commonly believed that doses lower than 40 to 50 Gy would not be useful in elective treatment of subclinical disease. Biological phenomena, such as presumed metastatic tumor cell burden and growth rate of micrometastases, which could guide the oncologist, had little or no role in the empirical development of adjuvant cytotoxic therapies. In this article, some assumptions regarding the biology of subclinical metastases are discussed and examined in the light of treatment responses reported from clinical experience. In particular, the importance of early initiation of adjuvant therapy can be appreciated as well as the significant reductions in the incidence of metastases that can be achieved even when doses less than 45 to 50 Gy have to be accepted if necessitated by normal tissue tolerance.