The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study.

PURPOSE: To answer the question whether a single fraction of radiotherapy that is considered more convenient to the patient is as effective as a dose of multiple fractions for palliation of painful bone metastases. PATIENTS: 1171 patients were randomised to receive either 8 Gy x 1 (n = 585) or 4 Gy x 6 (n = 586). The primary tumour was in the breast in 39% of the patients, in the prostate in 23%, in the lung in 25% and in other locations in 13%. Bone metastases were located in the spine (30%), pelvis (36%), femur (10%), ribs (8%), humerus (6%) and other sites (10%). METHOD: Questionnaires were mailed to collect information on pain, analgesics consumption, quality of life and side effects during treatment. The main endpoint was pain measured on a pain scale from 0 (no pain at all) to 10 (worst imaginable pain). Costs per treatment schedule were estimated. RESULTS: On average, patients participated in the study for 4 months. Median survival was 7 months. Response was defined as a decrease of at least two points as compared to the initial pain score. The difference in response between the two treatment groups proved not significant and stayed well within the margin of 10%. Overall, 71% experienced a response at some time during the first year. An analysis of repeated measures confirmed that the two treatment schedules were equivalent in terms of palliation. With regard to pain medication, quality of life and side effects no differences between the two treatment groups were found. The total number of retreatments was 188 (16%). This number was 147 (25%) in the 8 Gy x 1 irradiation group and 41 (7%) in the 4 Gy x 6 group. It was shown that the level of pain was an important reason to retreat. There were also indications that doctors were more willing to retreat patients in the single fraction group because time to retreatment was substantially shorter in this group and the preceding pain score was lower. Unexpectedly, more pathological fractures were observed in the single fraction group, but the absolute percentage was low. In a cost-analysis, the costs of the 4 Gy x 6 and the 8 Gy x 1 treatment schedules were calculated at 2305 and 1734 Euro respectively. Including the costs of retreatment reduced this 25% cost difference to only 8%. The saving of radiotherapy capacity, however, was considered the major economic advantage of the single dose schedule. CONCLUSION: The global analysis of the Dutch study indicates the equality of a single fraction as compared to a 6 fraction treatment in patients with painful bone metastases provided that 4 times more retreatments are accepted in the single dose group. This equality is also shown in long term survivors. A more detailed analysis of the study is in progress.

Radiation therapy for cancer of the piriform sinus. A failure analysis.

This paper analyzes the results of 109 piriform sinus (PS) cancers treated between 1973 and 1984 by surgery and/or external beam radiation therapy (EBRT) in a large comprehensive cancer center, and in particular tries to redefine the role of EBRT in the management of these tumors. At the time the policy was to start with EBRT to a dose of 40 Gy. A good response to a first series was to be continued by EBRT (RT-1); in case of poor responding tumors, the primary and neck were to be operated upon (RT-S). Poor responders unfit for S or those refusing S were also carried to a full course of EBRT (RT-2). The RT-S, RT-1, and RT-2 actuarial 5-year locoregional relapse-free survival (LR-RFS) and overall survival (OS) were 60%, 40%, and 20% and 40%, 30%, and 20%, respectively. In a multivariate Cox regression analysis the most important prognostic factor appeared to be N-stage, with hazard ratios of 1.16 (N1), 2.2 (N2), and 3.3 (N3). The RT-S treatment group fared best (hazard ratio 0.5). The risk of relapse for T3,4 was 1.3 times as high as opposed to T1,2. For stage I/II (19/21 treated by EBRT only), a LR-RFS and OS at 5 years of 60% and 40%, respectively, was observed. This analysis supports data for stage III/IV PS cancers to be treated by surgery combined with EBRT; in stage I/II there might be a role for EBRT alone. It is speculated that with further sophistication in RT-techniques, the locoregional control rates by EBRT alone could improve.

Interstitial hyperthermia using 27 MHz wire antennas and interstitial photodynamic therapy in a rat rhabdomyosarcoma: phantom and animal studies.

This paper deals with the interaction of interstitial hyperthermia (HT) and interstitial photodynamic therapy (PDT). Its main focus, however, is on a newly developed heating system; phantom studies as well as temperature-response data obtained from the in vivo experiments are presented. Heat was delivered by thin, flexible wire antennas operating at a frequency of 27 MHz. Measurements in muscle-equivalent phantom with infrared thermography were performed. Uniform heating over the inserted length of the antenna was obtained and impedance matching appears possible by simple variable air coils, thereby minimizing the reflected power to less than 20%. Light was obtained from an Argon-Dye laser system tuned to a wavelength of 625 nm at a dose rate of 75-100 mW per fiber to a total incident dose of 900 J from four linear light applicators. An experimental murine tumor (Rhabdomyosarcoma, type R-1) was transplanted in WAG/Rij rats and, after reaching an average diameter of 2 cm, the active component of haematoporphyrin derivative (HPD), Photofrin II, was injected intravenously. The tumors were subsequently implanted with four flexible catheters, through which either light or heat could be applied. Dose-response relationships for PDT alone, HT alone and PDT followed by HT were established with cure as endpoint. The animal experiments showed that with the use of low-frequency wires a good localized heat distribution in the tumors can be obtained. Moreover, this study showed that PDT and HT, in the proper sequence and only when optimal temperatures are reached, result in an augmented cytotoxicity on the tumor cells in vivo; i.e. a cure rate of 41% was obtained.