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A Coray

Publications and source records attributed to A Coray.

15 recordsLinked to original sources

Initial experience of using an active beam delivery technique at PSI.

At PSI a new proton therapy facility has been assembled and commissioned. The major features of the facility are the spot scanning technique and the very compact gantry. The operation of the facility was started in 1997 and the feasibility of the spot scanning technique has been demonstrated in practice with patient treatments. In this report we discuss the usual initial difficulties encountered in the commissioning of a new technology, the very positive preliminary experience with the system and the optimistic expectations for the future. The long range goal of this project is to parallel the recent developments regarding inverse planning for photons with a similar advanced technology optimized for a proton beam.

Humans↗

Proton dosimetry intercomparison based on the ICRU report 59 protocol.

BACKGROUND AND PURPOSE: A new protocol for calibration of proton beams was established by the ICRU in report 59 on proton dosimetry. In this paper we report the results of an international proton dosimetry intercomparison, which was held at Loma Linda University Medical Center. The goals of the intercomparison were, first, to estimate the level of consistency in absorbed dose delivered to patients if proton beams at various clinics were calibrated with the new ICRU protocol, and second, to evaluate the differences in absorbed dose determination due to differences in 60Co-based ionization chamber calibration factors. MATERIALS AND METHODS: Eleven institutions participated in the intercomparison. Measurements were performed in a polystyrene phantom at a depth of 10.27 cm water equivalent thickness in a 6-cm modulated proton beam with an accelerator energy of 155 MeV and an incident energy of approximately 135 MeV. Most participants used ionization chambers calibrated in terms of exposure or air kerma. Four ionization chambers had 60Co-based calibration in terms of absorbed dose-to-water. Two chambers were calibrated in a 60Co beam at the NIST both in terms of air kerma and absorbed dose-to-water to provide a comparison of ionization chambers with different calibrations. RESULTS: The intercomparison showed that use of the ICRU report 59 protocol would result in absorbed doses being delivered to patients at their participating institutions to within +/-0.9% (one standard deviation). The maximum difference between doses determined by the participants was found to be 2.9%. Differences between proton doses derived from the measurements with ionization chambers with N(K)-, or N(W) - calibration type depended on chamber type. CONCLUSIONS: Using ionization chambers with 60Co calibration factors traceable to standard laboratories and the ICRU report 59 protocol, a distribution of stated proton absorbed dose is achieved with a difference less than 3%. The ICRU protocol should be adopted for clinical proton beam calibration. A comparison of proton doses derived from measurements with different chambers indicates that the difference in results cannot be explained only by differences in 60Co calibration factors.

Algorithms↗

Proton dosimetry intercomparison.

BACKGROUND AND PURPOSE: Methods for determining absorbed dose in clinical proton beams are based on dosimetry protocols provided by the AAPM and the ECHED. Both groups recommend the use of air-filled ionization chambers calibrated in terms of exposure or air kerma in a 60Co beam when a calorimeter or Faraday cup dosimeter is not available. The set of input data used in the AAPM and the ECHED protocols, especially proton stopping powers and w-value is different. In order to verify inter-institutional uniformity of proton beam calibration, the AAPM and the ECHED recommend periodic dosimetry intercomparisons. In this paper we report the results of an international proton dosimetry intercomparison which was held at Loma Linda University Medical Center. The goal of the intercomparison was two-fold: first, to estimate the consistency of absorbed dose delivered to patients among the participating facilities, and second, to evaluate the differences in absorbed dose determination due to differences in 60Co-based ionization chamber calibration protocols. MATERIALS AND METHODS: Thirteen institutions participated in an international proton dosimetry intercomparison. The measurements were performed in a 15-cm square field at a depth of 10 cm in both an unmodulated beam (nominal accelerator energy of 250 MeV) and a 6-cm modulated beam (nominal accelerator energy of 155 MeV), and also in a circular field of diameter 2.6 cm at a depth of 1.14 cm in a beam with 2.4 cm modulation (nominal accelerator energy of 100 MeV). RESULTS: The results of the intercomparison have shown that using ionization chambers with 60Co calibration factors traceable to standard laboratories, and institution-specific conversion factors and dose protocols, the absorbed dose specified to the patient would fall within 3% of the mean value. A single measurement using an ionization chamber with a proton chamber factor determined with a Faraday cup calibration differed from the mean by 8%. CONCLUSION: The adoption of a single ionization chamber dosimetry protocol and uniform conversion factors will establish agreement on proton absorbed dose to approximately 1.5%, consistent with that which has been observed in high-energy photon and electron dosimetry.

Calibration↗

The 200-MeV proton therapy project at the Paul Scherrer Institute: conceptual design and practical realization.

The new proton therapy facility is being assembled at the Paul Scherrer Institute (PSI). The beam delivered by the PSI sector cyclotron can be split and brought into a new hall where it is degraded from 590 MeV down to an energy in the range of 85-270 MeV. A new beam line following the degrader is used to clean the low-energetic beam in phase space and momentum band. The analyzed beam is then injected into a compact isocentric gantry, where it is applied to the patient using a new dynamic treatment modality, the so-called spot-scanning technique. This technique will permit full three-dimensional conformation of the dose to the target volume to be realized in a routine way without the need for individualized patient hardware like collimators and compensators. By combining the scanning of the focused pencil beam within the beam optics of the gantry and by mounting the patient table eccentrically on the gantry, the diameter of the rotating structure has been reduced to only 4 m. In the article the degrees of freedom available on the gantry to apply the beam to the patient (with two rotations for head treatments) are also discussed. The devices for the positioning of the patient on the gantry (x rays and proton radiography) and outside the treatment room (the patient transporter system and the modified mechanics of the computer tomograph unit) are briefly presented. The status of the facility and first experimental results are introduced for later reference.

Cyclotrons↗

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↗

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↗

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↗

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↗

Dynamic pion irradiation of unresectable soft tissue sarcomas.

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, 3-dimensional spot scan treatment technique has been in use. To exploit this technique a special optimization treatment planning system has been designed. Of a total of 331 patients treated with pions from November 1981-December 1987, 35 were irradiated for unresectable soft tissue sarcomas. In 32/35 patients, tumor sites were retroperitoneal, pelvic or in the groin or thigh. Twenty-nine tumors had a maximum diameter of greater than 10 cm, 18 tumors of greater than 15 cm; 30 tumors had grade 2/3 and 32 Stage III B/IV A/IV B. Eight of 35 patients received a low pion total dose, 7-27 Gy. Twenty-seven patients received a total dose of 30-36 Gy, fraction size 150-170 cGy (90%-isodose), 20 fractions, 4 times per week. Of these 27 patients, severe late reactions appeared in five: 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 used). Seven of 27 patients had metastases at the beginning of irradiation. Three of 27 were treated with excisional biopsy, 9 with incisional biopsy or partial resection and in 15 patients biopsies were performed for histology only. The median follow-up of these 27 patients was 17 months (5-66). There was no progression in eight extremity/groin tumors but in 4 of 19 retroperitoneal/pelvic tumors. Three of these were marginal progressions. The actuarial 5-year rate of local tumor control is 64%; the actuarial 5-year survival rate of patients without metastases at the beginning of treatment is 58%. 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.

Adult↗

[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↗

[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↗

Sodium/calcium exchange in mammalian ventricular muscle: a study with sodium-sensitive micro-electrodes.

A method for mounting and rapidly perfusing small ventricular trabeculae (diameter around 250 micron) from either ferret or guinea-pig is described. Tension, membrane potential (Em) and intracellular Na activity (aiNa) were measured. aiNa was measured using Na-sensitive micro-electrodes. At room temperature (22-26 degrees C), [Na]o 155 mmol/l and [Ca]o 5.4 mmol/l, aiNa was 10.9 mmol/l +/- S.D. 4.2 mmol/l (n = 148). When [Na]o was reduced from 155 to 1.5 mmol/l contractures developed. These were about twitch height in guinea-pig but less than the twitch height in ferret. Associated with the development of the contracture there was a decrease in aiNa. The aiNa halved within 30 s. The decrease in aiNa was not influenced by changing pHo from 7.4 to 9.5, K-free solution or strophanthidin 50 mumol/l and was not passive since, even when the [Na]o was 1.5 mmol/l, the driving force for Na ions remained inward. The aiNa decreased if [Ca]o was increased and [Na]o decreased or vice versa. On the basis of these findings it is concluded that the decrease in aiNa is mainly due to Na/Ca exchange. Despite the large decrease in aiNa the [Ca]i, as monitored by tension changes, hardly increased. Since Ca uptake does occur in Na-free conditions in heart muscle it is proposed that the mitochondria take up Ca ions and so prevent an excessive rise in cytoplasmic Ca. Strophanthidin increased both aiNa and the withdrawal contracture, but collected results from a number of experiments showed no clear correlation between the initial aiNa and contracture amplitude. Strophanthidin may, therefore, have actions additional to increasing aiNa.

Animals↗

Cow ventricular muscle. I. The effect of the extracellular potassium concentration on the current-voltage relationship. II. Evidence for a time-dependent outward current.

1. The effect of [K]0 on the current-voltage relationship is described. In the negative potential range the curves cross over as [K]0 is increased. At positive potentials the curves re-cross so that in low [K]0 there is more outward current than in high [K]0. 2. Chord conductance has been calculated from the current-voltage relationship and this is taken as a measure of gK. It is shown gK is a function of both the potassium driving force (EM--EK) and [K]0. 3. Current-voltage relationships obtained by the voltage clamp technique have been compared to net current-voltage relationships obtained by phase plane analysis of the action potential. [K]0 is shown to have similar effects on both. 4. The effect of [K]0 at positive potentials suggests that delayed outward current during large depolarizing voltage clamp steps is due to an activation of a time-dependent outward current and not to potassium accumulation. An analysis of current tails also suggests the presence of a time-dependent outward current. 5. In contrast delayed outward current changes during small depolarizing voltage clamp steps are probably due to potassium accumulation. 6. Evidence is presented which indicates that inward current tails following depolarizing voltage clamp steps are due to potassium accumulation.

Action Potentials↗