BSD-2000 Published Clinical Studies

Phase I, II & III Clinical Studies that used the BSD-2000

Authors: M Romano, S Maluta, C Cordiano, G.G Delaini, M Genna, C Oliani, P Capelli, A Tomezzolli, C Manfrini, A.B Porcaro, M Gabbani, G Chierego
Publication: International Journal of Radiation Oncology, October 1, 2003Volume 57, Issue 2, Supplement, Pages S386–S387

To evaluate toxicity and pathological complete response rate in treating preoperatively rectal cancer patients by radiation dose escalation combined with RH + CT.

Between October 1988 and December 2002, 109 pts with primary rectal cancer underwent pre-operative radiotherapy (RT) associated with CT and RH. 57 out of 109 patients were assessed suitable for surgical conservative treatment. Clinical stages, as assessed by rectal ultrasound, were as follows T3N0 in 24 pts, T3Nx in 36, T3N???? in 33, T4N0 in 3, T4N???? in 4, T4Nx in 6, and T3NxM???? in 3. Radiotherapy was delivered with daily doses of 1.8-2Gy and the median total dose was 62 Gy. The median total dose in this series was delivered and escalated as follows: 54 Gy (range 50.4-60) in the firsts 22 pts, 56 Gy (range 54-66) in the second group of 44 pts (range 54-64), 62 Gy (range 54-66) in the third group of 22 pts, and 64 Gy (range 62-68) in the fourth group of 25 pts. Chemotherapy consisted of a continuous infusion of 5FU at the doses of 200 mg/m day for all the period of the radiation treatment in 74 pts, and was associated with a weekly bolus of Oxaliplatin at the doses of 45-65 mg/m for the first 4 weeks of the treatment in
35 pts. Regional hyperthermia was delivered by using the sigma 60 applicator BSD 2000 and was performed once weekly prior to radiotherapy for the first four weeks.

The treatment was well tolerated without any significant side effect. All but 6 patient had surgical resection of the tumour, which was complete in 94 cases and incomplete in 9. In 76 cases the surgeon was able to perform a conservative surgery. Six pts, with a clinical complete response refused surgery and were submitted to an intensive surveillance protocol. Pathological stages resulted as follows: no evidence of tumour in 28 pts, pTmic-pT2 pN0 M0 in 23, pTmic-pT2 pN????M0 in 3, pT3pN0M0 in 30, pT3pN????M0 in 11, pT3pN????M????(lung res.) in 2 pts, pT4 pN0 M0 in 2, pT4pN????M0 in 1, pT0pN0M????(liver res.) in 2, and pT3pN0pM????(lung res.) in 1. With regard of surgical complication, 27% had a radiological evidence of fistula (mainly in pts with colo-anal anastomosis) which delayed the time to restore the canalization and was not related to the radiation dose. All patients with residual disease where submitted to a 5-FU based chemotherapy. Of the 6 pts that refused the surgery, 5 are still disease free (mean follow up 24 months) after receiving a radiation dose of 66 Gy, while l pt, who received a radiation dose of 58 Gy, showed liver disease after 6 months and than died 8 months later. A multivariate analysis showed that radiation dose ???? 60 Gy, tumour length less than 3 cm were related to a higher rate of complete pathological responses. The actuarial survival at one, two, tree and four years is 100%, 95%, 90%, 80%, respectively. Two pts showed local recurrence that was successfully operated in one case.

In our experience this trimodality treatment for pts. affected by rectal cancer is effective. Dose escalation was well tolerated and may have contributed to an increase of the complete pathological response rate.