Biomedical subjects
Publications and source records attributed to J J Battermann.
Since November 1972 a pilot study of fast neutron therapy has been carried out in Amsterdam at the Antoni van Leeuwenhoek Hospital (the Netherlands Cancer Institute). With a d + T machine almost 200 patients were treated in 2 years. In this paper the preliminary results will be discussed.
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INTRODUCTION: The aim of this prospective study was to describe quality of life (QoL) in patients with locally advanced prostate carcinoma treated with conventional radiotherapy and to evaluate the influence of adding regional or interstitial hyperthermia. MATERIALS AND METHODS: All patients were irradiated using a CT-planned conventional three field technique, administering 70 Gy to prostate and vesicles. In two different phase I studies, hyperthermia was added to the radiotherapy. Twelve patients were treated with one interstitial hyperthermia treatment, lasting 60 min. Fourteen patients have been treated with five regional hyperthermia treatments, lasting 75 min each. In both hyperthermia studies, the body, bladder and rectum temperatures remained below safety limits. Patients treated with radiotherapy alone (n = 58) or combined with regional (n = 8) or interstitial hyperthermia (n = 12) completed the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire (C30 + 3), the EORTC prostate cancer module (PR25) and the Rand 36 health survey before treatment and 1 and 6 months after completion of treatment. Analysis of Variance (ANOVA) for repeated measurements has been performed to describe the data. RESULTS: All patient groups were comparable concerning patient characteristics. No significant interaction or difference in QoL has been noticed between the two hyperthermia patient groups and the patient group without hyperthermia. Therefore, all groups were analysed together (n = 78) to detect QoL changes in time. A deterioration of QoL has been measured from baseline to 1 month after treatment. Fatigue, pain, urinary symptoms, bowel symptoms and financial difficulties increased significantly. Social, physical and role functioning worsened significantly. No differences in QoL were measured 6 months after treatment compared to the baseline measurement, except for a decrease in sexual activity. CONCLUSIONS: After radiotherapy with or without hyperthermia only a temporary deterioration of QoL occurs, concerning social, psychological and disease related symptoms. Additional hyperthermia does not seem to decrease QoL.
A study was performed on regional hyperthermia for patients with locally advanced prostate carcinoma. The primary objective was to analyse the thermometry data with an emphasis on the possibility of replacing invasive thermometry by tumour-related intra-luminal thermometry. Fourteen patients were treated with a combination of conformal external beam radiotherapy (70 Gy) and hyperthermia. Hyperthermia was delivered using the Coaxial TEM system, one treatment per week, to a total of five treatments. Thermometry was performed in bladder, urethra, rectum and esophagus. Invasive thermometry in the prostate was carried out during one or two treatments for each patient by placing transperineally a central and a peripheral catheter. Heterogeneous temperature distributions were measured in the prostate. The mean average invasive temperature range was 1.1 degrees C. Due to the temperature heterogeneity and a limited number of thermometry sensors (mean 7, range 2-13), large variability between treatments and patients existed regarding achieved temperatures and dose. The mean invasive T90 was 40.2 +/- 0.6 degrees C and T50 was 40.8 +/- 0.6 degrees C. The mean Cum min T90>40.5 degrees C per treatment was 22 (range 0-50). Importantly, intra-luminal temperatures did not reliably predict invasively measured temperatures. Invasive thermometry, therefore, remains compulsory to calculate a thermal dose for an individual patient. Changes in temperature during treatment, measured by the urethral sensors, corresponded well with changes in temperature measured by the individual invasive sensors. Similar comparison of rectal temperature changes with intra-prostatic temperature changes was not as predictive. The similarity in temperature changes between the urethral and interstial sites, suggests that urethral temperatures are sufficient for treatment optimization. The SAR profile did not correspond with the temperature profile indicating heterogeneous perfusion. Although regional hyperthermia in combination with external beam radiotherapy for locally advanced prostate carcinoma is clinically feasible, the question on the importance of invasive thermometry remains.
The renewed application of fast neutrons in clinical radiotherapy has been stimulated by fundamental radiobiological findings. The biological effects of high LET radiation, including fast neutrons, are different from those obtained with x rays in at least three respects: the oxygen enhancement ratio, the sensitivity of cells at different phases of the cell cycle, and the contribution of sublethal damage to cell reproductive death. Furthermore, wide variations in relative biological effectiveness (RBE) have been observed for different tumors and normal tissues. Measurements of volume changes in human pulmonary metastases indicate that the RBE for slowly growing tumors which are generally well-differentiated is higher than that for poorly differentiated lesions. Six thousand patients have now been treated with fast neutron beams. The results of the clinical applications vary according to the method of application and to the type of cancer involved: treatment of inoperable malignancies of the salivary gland is very encouraging: the therapeutic gain is rather small for bladder and rectal cancers, soft tissue sarcomas and advanced carcinomas of the cervix; the responses of brain tumors are very disappointing. Most neutron radiotherapy applications have been less than optimal because of inadequate physical and technical conditions. Despite these difficulties, some interesting clinical data have become available. Due to the technical shortcomings, the possible advantages of fast neutrons are probably underestimated for many tumor sites. Well-designed clinical trials, preferably performed with high energy cyclotrons in clinical environments, will provide a decisive answer to the question of the usefulness of the new radiation modality.
Between August 1989 and July 1992 a total of 22 patients (64 treatments) with inoperable or recurrent deep seated pelvic tumours were treated with regional hyperthermia and radiotherapy. The 70 Mhz Coaxial TEM applicator with its characteristic open waterbolus was used as heating device. The main objective of this pilot study was to evaluate the feasibility, toxicity and temperature data. The results showed that the major treatment limiting factors were insufficient power and systemic stress. Local pain was observed in only 10% of all treatments. Most of the treatments resulted in elevated systemic temperatures with the overall mean maximum oesophagus temperature reaching 38.9 +/- 0.7 degrees C, however, in only 6% of these treatments this was found to be treatment limiting. From the measured data the following intratumoral temperatures were calculated: T90 = 39.9 +/- 1.0 degrees C; T50 = 40.7 +/- 1.0 degrees C; T10 = 41.4 +/- 1.0 degrees C. In addition, the overall mean average normal tissue temperatures were determined: Trectum = 40.8 +/- 0.7 degrees C; Tvagina = 41.3 +/- 0.9 degrees C; Turethra = 40.8 +/- 0.9 degrees C. The temperatures in normal tissue were frequently higher than in tumour, indicating that a large volume was heated. The open waterbolus allows strong cooling, but the strategy was changed during the study: higher systemic temperatures were allowed to improve the pelvic temperatures. This pilot study proved that the open waterbolus is clinically a success, because it offers patient comfort and SAR-steering by patient repositioning, and that regional hyperthermia with the Coaxial TEM is feasible.
The quality of temperature distributions that can be generated with the Multi Electrode Current Source (MECS) interstitial hyperthermia (IHT) system, which allows 3D control of the temperature distribution, has been investigated. For the investigations, computer models of idealised anatomies containing discrete vessels, were used. A 7-catheter hexagonal implant geometry with a nearest neighbour distance of 15 mm was used. In each interstitial catheter with a diameter of 2.1 mm a number of 1 up to 4 electrodes were placed along an 'active section' with a length of 50 mm. The electrode segments had lengths of 50, 20, 12 and 9 mm respectively. Both single vessel and vessel network situations were analysed. This study shows that even in situations with discrete vasculature and perfusion heterogeneity it remains possible to obtain satisfactory temperature distributions with the MECS IHT system. Due to its 3D spatial control the temperature homogeneity in the implant can be made quite satisfactory.
UNLABELLED: The aim of this study was to investigate the influence of the duration of waiting time between the end of induction chemotherapy and the start of radiotherapy on tumour control probability (TCP). PATIENTS AND METHODS: Twenty-three patients with inoperable stage III non-small cell lung cancer (NSCLC) received induction chemotherapy followed by radiotherapy. The mean waiting period between the end of induction chemotherapy and the start of radiotherapy was 80 days; in this period, the median tumour volume increased by a factor of about 6. The Poisson model for TCP and the linear-quadratic model were used to calculate changes in TCP in the waiting time. RESULTS: The 2-year survival of patients treated with curative intent was 8%, lower than the mean value of 26% derived from other studies. Assuming that radiotherapy started on the day of restaging or on the first day of radiotherapy (RT1), the calculated mean TCP at restaging was 13.3% and at RT1 was 0.5% for patients treated with curative intent. CONCLUSION: The calculated TCP decreased in the waiting period from 13.3 to less than 1%. Hence, the relatively long interval time between chemo- and radiotherapy had a deleterious effect on local control. We recommend the waiting time to be as short as possible.
AIM: To define the best sequence of radiotherapy and chemotherapy for inoperable stage III non-small cell lung (NSCL) tumours. MATERIALS AND METHODS: A systematic review was performed on the clinical results of radiotherapy, combined or not with chemotherapy, for inoperable NSCL cancer stage III. The mean median survival time (MST) and mean overall survival (OS) percentages were derived for radiotherapy only, for sequential and for concurrent chemo-radiotherapy. RESULTS: The mean median survival duration +/- standard deviation for radiotherapy only was 10.4 +/- 1.8 months. For sequential chemo- and radiotherapy it was increased to 13.0 +/- 1.2 months. When radiotherapy in the sequential regimen was accompanied by chemotherapy, the mean median duration was 15.8 +/- 2.6 months. For concurrent radio-chemotherapy it was further increased to 16.4 +/- 2.7 months. The mean 2- and 3-year overall survivals for radiotherapy alone, sequential and concurrent radio-chemotherapy were 17.1 +/- 4.6 and 10, 23.8 +/- 6.3 and 18.5 +/- 7.0, and 32.5 +/- 8.7 and 25.7 +/- 6.3%, respectively. CONCLUSION: Concurrent chemo-radiotherapy demonstrated increased efficacy over sequential chemotherapy and radiotherapy and should be the treatment of choice. Further improvements may be obtained by optimising the conditions for concurrent chemo-radiotherapy.