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Biomedical subjects

H Blattmann

Publications and source records attributed to H Blattmann.

At least 19 recordsLinked to original sources

Beam delivery systems for charged particles.

Heavy charged particle therapy, started at research institutes three decades ago, is now on the verge of entering a clinical phase. This phase has resulted from the evolution and development of various beam delivery systems and techniques with existing research accelerators and with newly built accelerators. For the first thirty years, heavy charged particle therapy was administered with a fixed horizontal beam line. In 1991, the first treatment with an isocentric gantry was administered. The development of the isocentric gantry, the newest beam delivery system, and clearly a consequence of all the experience gained at the earlier facilities has many advantages. It offers advantageous physical properties of the particles as well as being equal in the flexibility of dose delivery to the modern photon radiotherapy gantries.

Humans

Conformal radiotherapy for unresectable retroperitoneal soft tissue sarcoma.

Local tumor control remains a continuing challenge in the treatment of retroperitoneal soft tissue sarcoma. Though complete resection by means of wide excision or excisional biopsy can be performed in a minority of patients only, aggressive surgical approach remains the treatment of choice. Unresectable sarcoma can rarely be controlled by conventionally applied radiotherapy--only a few percent of patients survive. A superior dose distribution of external radiation is demanded in order to spare healthy tissue. The presumably greatest advantage will occur when radiotherapy is used preoperatively. The possible clinical gain of superior dose distribution is demonstrated by results of the dynamic, 3-D conformal pion radiotherapy at PSI. Between April 1983 and June 1988 a total of 21 patients were treated with high doses (greater than or equal to 30 Gy) for unresectable retroperitoneal soft tissue sarcoma. The follow-up time is 13-74 months, median 24. Fifteen patients were treated with 20 fx, and 19 patients were treated with fraction sizes of 150 or 165 cGy. Except for one patient with thrombocytopenia after chemotherapy, no treatment interruption was necessary. Five patients developed late reactions, caused also by surgery and chemotherapy: two intestinal obstructions, one liver abscess, one leg edema, and one superficial skin necrosis. Nine patients had laparotomy after pion irradiation, five for resection of the previous unresectable tumor; 3/5 sarcoma were completely resected. Morbidity rate after post-pion laparotomy did not increase. Three patients had local tumor progression, 1/3 inside the treatment volume. The actuarial five-year local tumor control rate of these unresectable retroperitoneal sarcoma is 60%, the actuarial five-year survival rate is 33%. Out of the 21 patients, 15 are alive, two have died from local progression, one from peritoneal progression, and three from metastases.

Humans

Effects of respiratory motion on dose uniformity with a charged particle scanning method.

A three-dimensional spot-scanning technique for radiotherapy with protons is being developed at the Paul Scherrer Institute. As part of the effort to optimize the design and ensure clinically useful dose distributions, a computer simulation of the dose deposition in the presence of respiratory motion was performed. Preliminary experiments have characterized the proton beam and the scanning procedure. Using these parameters, the computer program calculated the dose within a uniform volume of water in the presence of respiratory motion. Respiration amplitude, respiration period, respiration direction, number of fractions, size and position of the beamspots and rescanning multiplicity were systematically varied and the effect on the dose distribution determined. The dose uniformity is very dependent on the direction of the respiration relative to the three independent beam scanning directions. The dose uniformity decreases with increasing respiration amplitude, but has little response to changes in respiration frequency. Rescanning the volume, such as with fractionation, improves the dose uniformity roughly as the square root of the number of fractions. Broad, Gaussian beams result in better dose uniformity than narrow, sharply delineated ones, but produce slower dose fall-off at the edges of the scanned volume. Results of this work are being incorporated into the design of the system.

Computer Simulation

[Improving function by decortication. Functional studies with particular evaluation of lung perfusion scintigraphy].

The study presents functional and scintigraphic lung perfusion measurements before and after decortication of 9 patients treated for chronic pleural empyema with special emphasis to changes in perfusion scintigraphy. Preoperatively, the average vital capacity was 60% and the average FEV1 was 65% of the predicted. Perfusion of the affected side showed an average reduction to 22%. After decortication all functional data showed an improvement (average VC 78.5%, average FEV1 79.5%) the percentage of lung perfusion having increased to a mean of 37.8%.

Adolescent

Anaplastic astrocytoma and glioblastoma: pion irradiation with the dynamic conformation technique at the Swiss Institute for Nuclear Research (SIN).

Clinical phase I/II studies have been performed at the Swiss Institute for Nuclear Research (SIN) since February 1982. Fifty-two out of 249 patients accepted for pion treatment by the end of 1986 were treated for malignant glioma with high dose pion irradiation. A substantial influence of their radioresistance was expected from increased radiation quality due to the contribution of high LET particles from pion capture, and by the possibility of target volume shaping and dose distribution related to the dynamic spot-scan conformation technique. The patients' treatment followed a dose escalation program with total doses from 2720-3420 cGy, fraction sizes from 170 to 205 cGy (90% isodose, minimum target dose), and treatment times from 4 to 5 weeks. 12/52 patients received an accelerated treatment with 3280 cGy in 14-22 days. 49/52 patients are eligible: 3 with astrocytoma of clinical aggressive behaviour, 14 with anaplastic astrocytoma (median age 42 years), and 32 patients with glioblastoma (median age 52 years). 8/49 patients had total/subtotal tumour resection, 19 patients a stereotactic biopsy. The patients were divided into three groups according to total dose, and a fourth group which received the accelerated treatment. There was no statistically significant difference in the median survival rate between the four groups, which was 13 months for the non-glioblastoma patients and 9 months for the glioblastoma patients. No radiation necrosis and no demyelination was found in 17 patients (6 recraniotomies, 11 autopsies). In 10/17 patients, clearly identifiable tumour cells were not demonstrated. NMR findings showed the tumour-surrounding oedema mostly stimulated by tumour necrosis and tumour progression. From these findings, further dose escalation programs, together with a shaping of the target volume close to the tumour, are not contraindicated.

Adult

Decortication in chronic pleural empyema. Investigation of lung function based on perfusion scintigraphy.

The study presents measurements in spirometry and scintigraphic lung perfusion, before and after decortication, in 9 patients treated for chronic pleural empyema with special emphasis on measuring changes by perfusion scintigraphy. Preoperatively, the average vital capacity (VC) was 60% and the average FEV1 was 65% of the predicted. Perfusion of the affected side showed an average reduction to 22%. After decortication all functional data showed an improvement (average VC 78.5%, average FEV1 79.5%) the percentage of lung perfusion having increased to a mean of 37.8%.

Adolescent

Spot scanning for 250 MeV protons.

Protons have a long tradition in precision treatment of lesions of limited size at limited depth. Recently interest has developed in hospital based proton therapy accelerators, able to treat deep seated tumors. Heavy charged particles, and especially protons, are particularly suited to treat well localized tumors. Protons can be collimated as precisely as photons, but in addition have a well defined range. Protons are therefore predestinated for conformation radiotherapy also for larger target volumes. At the Swiss Institute for Nuclear Research a computer optimized treatment planning system has been developed for pion radiotherapy. The principle of this dynamic treatment technique can be adapted for proton therapy. It could prove to be a valid alternative to passive scattering for proton treatment especially of large irregularly shaped volumes. Dose calculations have been performed for specific cases using a 250 MeV pencil beam. The dose distributions and dose volume histograms have been compared with pion therapy. A horizontal experimental beam line, using a degraded 590 MeV proton beam of the PSI ring cyclotron, is set up to verify calculations in phantoms.

Humans

Repair inhibition in tumours irradiated with fast protons and negative pions.

Solid Ehrlich mouse tumours were irradiated in the 80 MeV proton beam of the Paul-Scherrer-Institute. The tumour volume was measured as a function of time after irradiation and two experimental endpoints were determined: local tumour control and minimal tumour volume after irradiation. The application of 2-deoxy-D-glucose (2-DG; 2 mg/kg) increased the radiation effect of protons by a factor of 1.4. The same tumour system was used with negative pions. Human tumours are usually irradiated with a mixed radiation produced by the "spot-scan-technique". This radiation quality was simulated in the mouse experiment by two successive irradiations with a spot of densely ionizing peak pions and a spot of sparsely ionizing plateau pions. Application of 2-DG raised the radiation effect due to the sparsely ionizing component again by a factor of 1.4. This indicates that clinical results in radiotherapy might be improved by application of 2-DG during the treatment.

Animals

Pion irradiation at Paul Scherrer Institute. Results of dynamic treatment of unresectable soft tissue sarcoma.

Since November 1981, when pion irradiation was introduced for deep seated tumors at the Swiss Institute for Nuclear Research (SIN; now Paul Scherrer Institute, PSI) a dynamic, three-dimensional spot scan application technique has been in use. To exploit this technique a special planning system for optimisation of the dose distribution has been designed. From November 1981 to December 1988 a total of 406 patients have been treated with pions. From April 1983 to October 1987 a total of 35 patients were prospectively treated for unresectable soft tissue sarcomas in a phase I/II-study. In 32/35 patients, tumor sites were retroperitoneal, pelvic or in the groin or thigh. 27 patients received a high, curative total dose of 30 to 36 Gy. After a median follow-up time of 19 months (13 to 68) the actuarial five-year rate of local tumor control for these 27 patients was 64%; the actuarial five-year survival rate of the 20 patients treated without metastases was 58%. Late reactions appeared in 5/27 patients: 2/8 patients with extremity/groin sarcomas (1/2 caused by biopsy) and 3/19 patients with retroperitoneal/pelvic sarcomas (one a skin reaction after Actinomycin-D, one a small bowel reaction after 36 Gy, a dose no longer given). Dynamic spot scan pion irradiation proves to be a successful treatment technique for unresectable sarcomas with a high rate of tumor control and a very low rate of severe late reactions.

Aged

Radiation physics.

A review is presented of the recent literature in the areas of physics which deal with radiation effects on man and animals. Some consideration is given to natural and artificial radiation sources such as cosmic rays, radon and high energy accelerators. The interaction of radiation with matter is treated if it is related to an energy deposition pattern relevant to biological effects. Dosimetry is also treated, with special emphasis on papers dealing with spatial dose distribution on a microscopic level, and radiobiological models relating the energy deposition pattern to biological effects are cited. New techniques in the medical application of radiation in diagnostics and therapy are briefly mentioned.

Animals

Biological effectiveness of neutrons and pi-mesons in gut, bone, and transplantable tumours.

At the Munich RENT-facility a screening project was performed to define the biological characteristics of a fission neutron beam envisaged for radiotherapy. The quantitative endpoints used were jejunal crypt survival, late rectal stenosis in rats, osseous healing in traumatized rat femur and regrowth delay of murine transplantable tumours. The results obtained in normal tissues (with the possible exception of bone) demonstrate a high RBE, in accordance with the well documented dependence of RBE on neutron energy. The RBE-values measured in tumours after single dose treatment endorsed the high effectiveness, although--as has been the case with other beams--they gave no conclusive evidence of a therapeutic advantage. Nevertheless, the specific beam characteristics, i.e. a high RBE at the surface and a fast decline of the biologically effective depth dose suggest possible advantages of the RENT beam when applied in the treatment of selected superficial tumours.

Animals

[Pion radiation therapy of non-resectable bone- and soft tissue sarcomas at the Swiss Institute for Nuclear Research].

A dynamic, tumor conforming treatment technique ("spot scan") for deep-seated tumors using pions (negative pi-mesons) has been in use at the Swiss Institute for Nuclear Research (SIN) since November 1981. This technique, with a favorable integral dose distribution, allows curative irradiation especially for large, unresectable tumors in the retroperitoneal and pelvic region. Between 1983 and 1986, 26 patients with sarcomas were treated: 18 had soft tissue sarcomas and 8 bone sarcomas. The tumor volumes ranged from 36 to 3400 cc. After previous therapy (23/26 patients) 14 out of 23 patients had progressive disease. In 20 fractions over 5 weeks a total dose of 30-36 Gy (90%-isodose) was administered. In a follow-up period of 9-50 months (median 14 months), the two year local control rate (Kaplan-Meier) for the soft tissue sarcomas was 93.3% and the two year survival rate 67.9%. Each of the 6 patients with bone sarcomas treated with curative intent showed clinically local tumor control. After a total dose of 30-36 Gy, no severe radiation induced morbidity was found.

Adolescent

An intercomparison of two dynamic treatment techniques, ring scan and spot scan, for head and neck tumors with the Piotron.

An evaluation of the ring scan and the spot scan was made for the pion irradiation of head and neck tumors with the Piotron. For the geometry of the Piotron, with its 60 radially converging beams, two scanning techniques have been developed, ring scan and spot scan. They have different characteristics concerning achievable dose distributions and sensitivity to tissue inhomogenities. The optimized 3-dimensional dose distributions for the treatment with ring scan and spot scan techniques were calculated for two examples of the target volume. The comparison of the dose distributions has shown that the ring scan is better in sparing normal tissues than the spot scan for a simple shape target volume but not for an irregular shape target volume with the present status of the technique. The irradiation time needed for the ring scan is longer, for the present examples three times, than for the spot scan. From the practical view point the spot scan is preferable to the ring scan for the treatment of head and neck tumors with the Piotron.

Elementary Particles

[Pion radiotherapy of unresectable soft tissue sarcomas at the Swiss Institute for Nuclear Research].

The Swiss Institute for Nuclear Research SIN at Villigen is one of the three centres in the world (LAMPF, Los Alamos; TRIUMF, Vancouver) where pion therapy is possible. A dynamic, tumour conforming spot scan technique for the treatment of deep-seated tumours has been in use since November 1981. With this technique with a favorable integral dose distribution, curative irradiation also of advanced tumours in the retroperitoneum and pelvis is possible. Only at SIN, the treatment of non-resectable soft tissue sarcomas with pions is part of the clinical program. Between 1983 and 1985 totally nine patients were treated, 1/9 with three manifestations, 1/9 with palliative intent. In 20 fractions over five weeks (four fractions a week) total doses of 30 to 36 Gy (90% isodose) were applied. In a follow-up period of eleven to 43 months (median 18 months) only 1/10 tumour manifestations treated with greater than or equal to 30 Gy failed locally. The two-year survival rate (Kaplan-Meier) is 56%. Metastases were the cause of death in 3/5 patients, 1/5 heart disease, 1/5 local tumour progression. Even though 9/11 tumours were located in the retroperitoneum or pelvis, no radiogenic morbidity of the bowel was found. These preliminary results stimulate the intensification of this clinical program. 1986 the same number of patients with non-resectable soft tissue sarcomas was treated as in the whole period 1982 to 1985 before.

Adolescent

Pionic carbon/oxygen capture ratios in blood and muscle tissue of pig.

The pionic carbon/oxygen capture ratio for the blood and muscle tissue of a pig was measured using an intrinsic Ge detector in order to investigate possible explanations for an enhanced lesion observed in the autopsy of pion-irradiated patients. Pure iron was also irradiated in order to determine the energies and intensities of pionic x-rays from iron. It was expected that some of them originated from haemoglobin and could be observed in the spectrum for a blood sample. TE plastic (Shonka A-150) and Lucite were also investigated for comparison with other work.

Animals

Variations of pion RBE in a volume with an asymmetric beam configuration.

The relative biological effectiveness for the radiation response of mouse jejunum for pions was determined in a clinically relevant asymmetric treatment geometry. A cylindrical volume of 570 ccm, with mouse holders in proximal and distal positions, was irradiated by spot scan technique with a sector of 31 concentric pion beams. The physical dose distribution within the treatment field was homogeneous and the average dose rate was 8.5 cGy/min. The aim was to determine RBE differences between the proximal and distal edge of the field and to compare it with the predictions. The RBE, relative to 200 kVp X-rays, was 1.3 for proximal position and 1.4 for the distal one. The results are in agreement with the calculations of the therapy planning computer program and with the microdosimetric characteristics at the two positions. The variation of the RBE is smaller than for the same field irradiated by a single pion beam.

Animals