Late results in patients treated with Pi-mesons for bladder cancer

Abstract

Background. The treatment of bladder cancer with 60 converging pion beams was expected to have certain dose‐distribution advantages with possibly fewer side effects than other high linear‐energy‐transfer (LET) radiation therapies, such as neutrons. Results. Early results were promising: 20 of 24 (83%) evaluable patients with sessile invasive bladder carcinomas had clinically complete responses. However, only 3 of 10 (30%) evaluable patients with superficial bladder tumors had clinically complete responses. This article reports the long‐term follow‐up (6–8 years) of these patients with emphasis on the late side effects of pion radiation therapy. Thirty‐eight of the 41 (93%) patients treated died after a median survival time of 17 months (range, 4–98 months). Seventeen (45%) died of metastatic disease (in two instances, this was combined with a local recurrence) 5–27 months after radiation therapy. Four (10%) died of locally progressive disease, and eight (21%) died of late side effects of radiation therapy 9–98 months after treatment. All these patients were treated with more than 33 pion Gy and had generally a symptom‐free interval of 9–18 months. The observed side effects were severe, consisting of chronic inflammation and vascular damage in the pelvic region often followed by ulceration, fistulas, and perforations throughout the intestines. In 11 patients, cystectomy and urinary diversion was necessary because of excessive fibrosis and bladder shrinkage. In eight patients, a colostomy was required for stenotic inflammatory disease, necrosis, and perforations of the intestines. The remaining nine patients (24%) died of causes unrelated to the primary disease 4–60 months after radiation therapy. Conclusions. The results of the first Phase I/II trial using the Swiss piotron showed a high complete response rate in patients with sessile bladder cancers but also a high incidence of local recurrences and severe, in some instances lethal side effects. Although it is expected that these results will be the basis for future improvements, particularly regarding dosing and fractionation, this experience emphasizes the need for a sufficiently long observation period before reaching conclusions about any high LET treatment, such as neutron, pion, or heavy ion radiation therapy.

An Evaluation of the Results of Neutron Therapy Trials

“…The RBE for late effects is, in the case of the bowel, much higher than for early morbidity (29). The late morbidity experienced after pion therapy for bladder cancer has also been shown to be unacceptably high (30). An RTOG trial, (81-lo), of pre-operative photon or mixed schedule irradiation before cystectomy for bladder cancer did not recruit more than about 3 patients and was closed in 1984, without any useful data being obtained.…”

Superficial bladder cancer

“…It appears that superficial bladder cancer may be more resistant to radiation therapy than muscle-invasive disease. In a study of pion beam radiation, an encouraging 83% of 24 patients with invasive cancer had complete response compared with only three of 10 patients with superficial bladder cancer [19]. Unfortunately, 93% of the patients died after a median of 17 months, many of treatment-related side effects.…”

European Developments in Radiotherapy with Beams of Large Radiobiological Effectiveness

“…Although the dose improvement at the end of the range could be confirmed in physics measurements, the clinical trials performed at PSI (Switzerland) at the 'Piotron' facility in the years from 1980 to 1993 could not demonstrate an improved cure rate and the pion trials were terminated worldwide after the treatment of some 800 patients. [6][7][8] Today the proposed use of antiprotons represents in many aspects a revival of the basic ideas of pion treatment but, considering also cost and complication, its advantages with respect to the multiply charged ions discussed in this paper are by far not obvious. The way in front of the proponents of this large radiobiological effectiveness therapy is still long but it has to be underlined that recently an interesting paper has been published on the measurements performed at CERN on the RBE of stopping antiprotons.…”