A pilot study of accelerated preoperative hyperfractionated pelvic irradiation with or without low-dose preoperative prophylactic liver irradiation in patients with locally advanced rectal cancer.

BACKGROUND AND PURPOSE

To evaluate the feasibility of low-dose preoperative prophylactic liver irradiation (PLI) combined with preoperative accelerated hyperfractionated pelvic irradiation (HART) in patients with locally advanced rectal cancer.

PATIENTS AND METHODS

Between 1999 and 2003 62 patients were enrolled: 38 (61%) received HART and 24 (39%) HART+PLI. The pelvis was irradiated twice a day, with a minimal interfraction interval of 6h: the total dose of 42 Gy was given in 1.5 Gy per fractions over 18 days. The PLI (14 Gy in 10 daily fractions of 1.4 Gy) was given simultaneously with the morning fraction of HART. Twenty patients (32%), including 7 in PLI group, received 5-Fu based postoperative chemotherapy.

RESULTS

In general, acute normal tissue reactions appeared tolerable irrespectively of PLI. Six to twelve months after completion of combined therapy the mean ALAT levels in patients treated with HART alone (25 pts), HART+chemotherapy (13 pts), HART+PLI (17 pts), and HART+PLI+chemotherapy (7 pts) were 15, 21, 26 and 55 IU/l, respectively. A mild increase of ALAT levels observed in the HART+PLI+chemotherapy sub-group was non-symptomatic. Three-year actuarial loco-regional control rate in a group of 62 patients was 94%. None of the patients who received PLI developed metastases during the follow-up, compared to 10 out of 38 patients (26%) with no PLI. A difference in metastases-free survival in favor of HART+PLI can be, however, attributed to selection of patients for PLI who were in better general health and stage of disease than those treated with HART.

CONCLUSIONS

Further use of PLI may be limited due to asymptomatic, but detectable biochemical changes of liver function when PLI is sequentially combined with chemotherapy. HART, on the other hand, provides acceptable rate of local control, and is well tolerated, also when combined with postoperative chemotherapy.