GROWTH FRACTION DEFINED BY KI-67 IMMUNOSTAINING AS A SELECTION FOR COMBINED THERAPY OF RADIATION AND MITOMYCIN-C IN LOCALLY ADVANCED CERVICAL CANCERS
Keywords:
Cervical cancer, Radiation response, Growth fraction, Ki-67 immunostaining, hypoxic tumor, Mitomycin-CAbstract
OBJECTIVE To study the relationship between low growth fraction and hypoxic condition of the tumor that allows bioreductive agents, such as Mitomycin-C (MMC), to work more effectively in such environment. A prospective study was conducted at our institution between October 1994 and October 1996.
MATERIALS AND METHODS Sixty-one locally advanced cervical cancer patients with a low growth fraction as defined by Ki-67 immunostaining (Ki-67 index < 40%) were randomized into two groups. The first group of 30 patients were treated with irradiation alone and the second group of 31 patients were irradiated in combi- nation with MMC. External irradiation was given with Linear accelerator or Co-60 to the whole pelvis, 180 cGy/fraction, 5 days a week, with a total dose of 5040 cGy in 5.5 weeks. This was followed by intracavitary afterloading irradiation within 2 weeks using High Dose Rate Co-60 sources, two applications, one week interval with a dose of 850 cGy at point A in each application. MMC was concurrently given as bolus injection on the first day of external irradiation and the first intracavitary application with a dose of body surface 15 mg/m2 of each injection.
RESULTS Response of the tumors was determined within 3 months upon com- pletion of irradiation. In the first group, complete response was achieved in 11 of 30 patients (36.6%), while in the second group, this was achieved in 26 of 31 patients (83.8%), showing significant difference between the two groups (p=0.004). No marked difference of acute toxicity was observed.
CONCLUSIONS The results of the treatment suggested that low growth fraction tumors, which assumed as relatively hypoxic tumors, could be improved in their radiation response by Mitomycin-C.
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