Local tumor recurrence after radiation therapy is due primarily to the fail
ure to eradicate all of the tumor cells within the treatment fields, Theore
tically, all cancers could be controlled locally ifa sufficiently high radi
ation dose could be delivered to a treatment volume that encompassed all of
the tumor cells, In practice, however, the administration of a radiation d
ose high enough to sterilize all of the tremor cells would pose an unaccept
ably high risk of severe damage to normal tissues. Technologic improvements
in the delivery of therapeutic radiation have led to some improvements in
the therapeutic ratio (ie, the ratio of the dose required to eradicate ever
y tumor cell to the dose that produces unacceptable normal tissue toxicity)
. Further significant improvements in the therapeutic ratio will derive fro
m an understanding of the mechanisms governing the sensitivity of malignant
and normal cells to radiation. Part 1 of this two-part article reviews the
clinical and tissue kinetic factors that govern the sensitivity of normal
tissues and organs to ionizing radiation. Part 2, which will appear in next
month's issue, describes recent insights into the cellular and molecular p
athways that determine the sensitivity of normal cells and tumor cells to r
adiation.