Rational for seven day per week accelerated radiation schedules

Radiation Oncology

150

??Biology ??Physics

October 1984, Volume 10, Sup. 2

rad. The biphasic clearance curves, corrected for physical decay, are least-squares fitted to a sum of two exponentials. In unirradiated skin, the initial rate constant, y 2 (fast component), is in the range 0.04 to O.l-min-I. The second constant, y 1 (slow component) has control valves from .003 to -05 min-I. These clearance rates reflect the functional status of the dermal microvasculature or lymphatics. A transient decrease is seen in the fast component, with return to control levels by approximately day 90. The slow component decreases in time correlating with the degree of dermal fibrotic change. The amount of fibrosis increases with increasing irradiated volume. Minimum clearance rates in large fields are several times smaller than those in small fields for both the fast and slow components. This decrease in clearance is anticipated from a previous analysis of isoeffect data. It supports a model of skin function in which epidermal basal cells, capable of increased proliferation rates, return to control population levels by day 36, even following large exposures. The subsequent fibrotic changes leading to necrosis result from disruption of vascular continuity in the dermis, which in turn depends on endothelial cell survival. Accepting that changes in y I reflect changes in flow rates, these results support our previous suggestion that long term skin tolerance is more dependent on vascular integrity in the dermis than on basal cell kinetics.

1007 RATIONALE Ronald

FOR SEVEN DAY PER WEEK ACCELERATED

M. Shymko,

Ph.D.,

City of Hope National

James

Medical

A. Lipsett, Center,

RADIATION M.D.,

Duarte,

CA

Kanta

SCHEDULES R. Oesai,

M.D., John 0. Archambeau,

M.D.

91010

Accelerated fractionation schedules giving multiple 180-200 rad exposures daily 5 days/week are being used to overcome the effects of cell proliferation in rapidly growing tumors. However, such schedules may be suboptimal if tumor cell proliferation proceeds rapidly through the weekend hiatus of about 72 hours between the Friday and Monday exposures. Another way to achieve accelerated delivery of radiation that can potentially reduce weekend proliferation effects is to give one exposure daily and to treat 7 days per week. This schedule has several other possible advantages over those using multiple daily exposures. First, the time between exposures is longer than for multiple daily exposures, so that more normal tissue repair of radiation injury can take place. Second, because normal tissue repair will be essentially complete between exposures, small variations in the timing of the exposures and/or inter-patient differences may be less significant. Third, the interval between exposures is constant, so that radiobiological variation between exposures is more symmetric. Fourth, patients come to the radiation therapy department only once per day, rather than coming two or more times or remaining in the department for several hours. This may be less of a hardship for many patients, and improves patient acceptance of treatment. To identify situations where 7 day/week irradiation may gfve improved results, we have simulated the tumor and normal tissue responses for 7 vs 5 day/week schedules, for one or multiple exposures per day, and have compared the predictions with observations in swine skin and in clinical trials of 7 day/week irradiation using exposures of 180-200 rad. Dose survival parameters, repair capability, repair half-times, proliferation rates and radiation-induced division delays were chosen as relevant variables. Rased on our results with swine skin irradiated 5 or 7 days per week, a cell density dependent switch in proliferation rate was included in the formulation. The results show that 7 day/week irradiation can be useful in a number of circumstances: 1) Tumor proliferation is rapid. 2) Tumor cell proliferation rate recovers in a short time after irradiation. 3) Normal cell repair times are sufficiently long, while tumor repair is minimal. 4) Normal, but not tumor, 5) Normal cell proliferation rate switches to a hiah value when cell densitv droos below a threshold level. cell proliferation is less inhibited by &ccessive small radiation doses than tumor cell proliferation. Our swine skin measurements and clinical results suggest that some of these conditions exist in these systems. The clinical data show that normal tissues tolerate the 7 day/week schedule well and that cancer control can be achieved. These results indicate a role for 7 day/week irradiation.

1008 SWINE EPIDERMAL POPULATION PROLIFERATION DURING SCHEDULES DAYS/WEEK TO 6000 RAD: A PRE-CLINICAL EVALUATION John 0. Archambeau, Department

M.D., Douglas

of Radiation

Research,

Hauser,

B.A., Ronald

City of Hope National

USING DAILY EXPOSURES

M. Shymko, Medical

5 DAYS/WEEK;

AND 7

Ph.D.

Center,

Duarte,

CA

Proliferation of cancer cells in the interim between daily exposures is cited to justify the use of multiple daily 180-220 rad exposures given 5 days a week for cancers with a rapid doubling time. While cell proliferation is implied, it has not been documented. If the argument is valid, why not irradiate over the weekend which is 72 hours long (Fri.-Sat.; Sat.-Sun.; Sun.-Mon.)? This hiatus is 3/7ths (43%) of