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PubMed1982

Mixed beam radiotherapy and combination chemotherapy in localized pancreatic adenocarcinoma-preliminary results.

A pilot study of mixed beam radiotherapy (fast neutrons alternating with photons) followed by combination chemotherapy with SMF (streptozotocin, 5-fluorouracil, mitomycin C) in localized pancreatic cancer was performed. Thirteen patients were treated and a median survival of 10.0 months was noted (range 5-30+). Toxicity was mild to moderate. Further studies of sequential radiation and chemotherapy are indicated.

Adenocarcinoma↗
PubMed1982

An interpretation of some biological results obtained in range-modulated negative pion beams.

Recent biological date show little change in relative biological effectiveness (RBE) across the peak region of range-modulated pion beams in contrast to previous works which showed increasing RBE with depth. These biological results are shown to be consistent with each other and with previously measured microdosimetric data. The differences are attributed to differences in the lateral spread of the beams. Large lateral distributions result in an increased dose as a result of neutrons emitted in pion "stars" an effect that is quantified using a high-energy neutron transport code. For a large beam which is of the type used in therapy, the neutron dose is as much as 50% of the total "star" dose and of the high linear energy transfer (LET) dose, this percentage increasing peak volume. Preliminary measurements are in agreement with the calculated results. The rapid increase in neutron dose with field size should be an important factor in pion treatment planning.

Animals↗
PubMed1982

Radiobiology of pions at TRIUMF.

Radiobiological studies at TRIUMF of the effects of pion beams have been carried out using cultured cells, mice and pigs. CHO cells in gel/medium were used for RBE determinations throughout the dose distributions. The RBE was shown to increase with depth in the stopping region, while the average RBE value decreased with increasing width of the stopping peak and also increased with increasing field size. The results suggest that the effects of peak width and field size will approximately cancel out when treatment volumes are changed, provided that all three dimensions are changed more or less proportionally. The peak center RBE values ranged from 1.2-1.3 for single doses. The oxygen enhancement ratio (OER) for pions was 2.2 compared to 2.8 for X rays. Split dose recovery was found to be somewhat reduced in the peak region. In vivo studies with mouse and pig skin have been done for 1 to 20 fractions. For mouse skin, pions showed an RBE of 1.5-1.6 for fraction numbers greater than 10. The RBE for pig skin was 1.4 for early reactions, but it may be higher for medium term reactions.

Animals↗
PubMed1982

Radiobiology of pions at LAMPF.

Recent radiobiology data for pion beams used in therapy are presented. The biological systems used were cultured cells suspended in gelatin and intestinal crypt assay. The importance of fast neutrons from pion stars in large treatment volumes is discussed. The data for compensating the depth dose distribution to produce uniform cell killing across the peak region are presented. The changes in biological effectiveness with peak width for pion beams (unlike heavy ions) are small because of fast neutron contribution from pion stars. The need for innovative radiobiology programs to guide high-LET radiotherapy is discussed.

Animals↗
PubMed1982

Pion radiotherapy at LAMPF.

Clinical investigations of pi meson radiotherapy were conducted by the Cancer Research and Treatment Center of the University of New Mexico and the Los Alamos National Laboratory from 1974 until 1982. Two hundred and thirty patients have been treated for a variety of locally advanced primary and metastatic neoplasms. One hundred and ninety-six patients have been followed for a minimum of 18 months. Crude survival data range from 11% for unresectable pancreatic carcinoma to 82% for Stages C and D1 adenocarcinoma of the prostate. Acute tolerance of normal tissues is approximately 4500 pion rad in 36 fractions over 7 weeks. Severe chronic reactions have appeared with increasing frequency after doses in excess of 4000 pion rad.

Adenocarcinoma↗
PubMed1982

Pions, Vancouver.

Clinical treatments at TRIUMF started in November, 1979. Ten patients with malignant subcutaneous nodules had 14 lesions treated with pions and 37 other nodules treated with 280 kV X rays. Three different fractionation regimens were used with X ray doses spanning the expected RBE range of pions. The RBE for pions for acute skin reaction for 10 fractions had a mean value about 1.5, while for 3 fractions it was 1.3 maximum. No dissociation of acute and late skin effects was seen with follow-up to 27 months after treatment. Phase 1-2 studies of Pion-Boost Therapy for patients with glioblastoma multiforme will begin in May, 1982. These will be followed in August with treatments of advanced pelvic malignancies using pions only. The existing beam line at TRIUMF will be upgraded and commitments have been given to go to higher beam currents. As a result, the dose rate should increase by a factor of at least two, allowing treatment of clinically relevant volumes in acceptable times by 1983-1984.

Brain Neoplasms↗
PubMed1982

The PIOTRON: initial performance, preparation and experience with pion therapy.

The PIOTRON is a large solid angle superconducting channel built for the use of negative pi-mesons in radiotherapy. The pions are produced by protons of 590 MeV striking a target of molybdenum or beryllium. The pions are divided into 60 channels and deflected twice to enter the treatment volume radially. The momentum and the momentum band for all 60 channels can be chosen and the beam spot of Bragg peak pions at the isocenter of the applicator is a few centimeters in each direction. Dynamic scanning can thus achieve 3-dimensionally shaped treatment volumes. Two different methods are available: the ring scan, using changes of pion range; and the spot scan, involving translation of the patient through the fixed beam spot. Dose distributions of individual and multiple beams were plotted in a cylindrical water phantom. Radiobiological experiments with mammalian cells in gel and with mouse feet were performed. A special beam geometry using a sector of 15 beams was selected for the first treatments of patients with metastatic skin nodules. Six patients were treated. Acute skin reactions were scored and compared with those from orthovoltage therapy with comparable beam geometry. The RBE for 10 fractions is between 1.4 and 1.5. The next step involved treatment of patients inside water-bolus rings in preparation for dynamic therapy. Patients were then treated with the spot scan dynamic mode in the water bolus. The initial responses and reactions are favorable and confirm the feasibility and accuracy of dynamic pion therapy.

Elementary Particles↗
PubMed1983

Biopsy and definitive radiation therapy in stages I and II carcinoma of the female breast.

One hundred-twenty patients with Stages I and II carcinoma of the female breast were treated by biopsy followed by definitive radiation therapy without mastectomy. The breast received 4500-5000 cGy (rad) using a 6 MV linear accelerator followed by a supplement to the area of the primary tumor of 2000 cGy (rad) using electrons in 99 patients (83%) and interstitial implantation in 21 patients (17%). Local recurrence was not recorded in the 43 patients with Stage I disease, while three of 77 patients (4%) with Stage II disease suffered a local recurrence. The actuarial five-year relapse-free survival was 91% and 60% in Stages I and II respectively. Cosmetic results were considered excellent by both physician and patient in the majority of cases. Axillary dissection was the recommended method of staging the axilla but was noted to be more morbid than axillary sampling. Electrons may be as effective as interstitial implantation as a means of supplementation following external beam therapy if specific guidelines are followed.

Actuarial Analysis↗
PubMed1983

Biological effects of pion therapy beams: I. Cultured cells.

The results of cell killing by pion beams of different peak widths, ranges and sizes used in therapy are reported. Cultured hamster cells (V79) suspended in gelatin were used. The results indicate that: 1) there are no significant differences in cell-killing between pion beams of different ranges but of the same peak width; 2) there is a slight decrease in biological effectiveness with increasing peak width; and 3) the range-modulation functions used to produce uniform cell-killing are satisfactory for intermediate-range pion beams, but slight corrections may be required for shorter- and longer-range pion beams.

Animals↗
PubMed1983

Neutron therapy for head and neck cancer: II. Further follow-up on the M. D. Anderson TAMVEC randomized clinical trial.

Between January 1977 and February 1980, 95 patients with inoperable squamous carcinomas of the head and neck were treated in a two-armed randomized clinical trial comparing 1) mixed schedule irradiation using two neutron and three photon fractions per week and 2) standard photon irradiation. Complete tumor regression was achieved in 80% of patients treated with mixed-schedule irradiation, and in 68% of patients treated with photons. The local control rate was 44% in patients treated with mixed-schedule irradiation and 41% in patients treated with photons. There were four complications of treatment in each treatment arm. Absolute survival was 20% with mixed-schedule treatment and 17% in photons. Actuarial analysis shows superior local control and survival rates with mixed-schedule irradiation over photons only in the first two years.

Carcinoma, Squamous Cell↗
PubMed1983

Fast neutron irradiation of metastatic cervical adenopathy: the results of a randomized RTOG study.

Between 1977 and 1982, 199 evaluable patients with measurable cervical adenopathy were entered on a prospective, randomized RTOG study evaluating the use of fast neutrons in treatment of advanced, inoperable squamous cell carcinomas of the head and neck region. One hundred-eleven patients were randomized to receive mixed beam radiation therapy, and 88 were randomized to the photon control treatment. The complete response rates were 86% for mixed beam vs 75% for photons for Stage N1 nodes, 62% for mixed beam vs 48% for photons for Stage N2 nodes, and 63% for mixed beam vs 53% for photons for N3 nodes. The percents of patients remaining free of their adenopathy for two years were 78% for mixed beam vs 55% for photons for Stage N1 nodes, 39% for both mixed beam and photons for N2 nodes and 24% for mixed beam vs 13% for photons for N3 nodes. The median disease-free status was 20.3 months for mixed beam treated patients and 6.4 months for photon-treated patients. Patients who had clearance of cervical adenopathy survived significantly longer than those who did not.

Carcinoma, Squamous Cell↗
PubMed1983

The effect of small radiation doses on the rat spinal cord: the concept of partial tolerance.

To evaluate the tolerance of the rat spinal cord to small radiation doses per fraction, an increasing number of fractions is required for induction of paralysis. The assessment of doses of 1-2 Gy, as used in the clinic, would require that over 100 fractions be given. The validity of replacing part of a fractionated irradiation of the spinal cord by a single large dose has been tested. Fractionated irradiation doses with 18 MeV X rays were followed by a "top-up" dose of 15 Gy as a single treatment. This is the fraction size of a treatment with two irradiation doses leading to paralysis in 50% of the animals (ED 50). Fractionated treatments were carried out with 2, 5, 10 and 20 fractions followed by the top-up dose of 15 Gy. The isoeffect curve, as a function of the number of fractions, has the same slope as experiments performed without top-up dose. The results show that the quality and quantity of cellular repair is not modified when part of a multifractionated exposure is replaced by a larger top-up dose. An important consequence of this finding is, that in treatments with unequal fraction sizes, the partial tolerances can simply be added. Since a top-up dose can replace a sizable number of irradiation treatments, its application will allow investigations of the extent of sublethal damage repair for fraction sizes as low as 1 Gy.

Animals↗
PubMed1983

Pathologic effects of fractionated fast neutrons or photons on the pancreas, pylorus and duodenum of dogs.

Thirty-nine adult male Beagles received either fast neutron or photon irradiation to the right thorax to determine the relative biological effectiveness (RBE) of fast neutrons on normal pulmonary tissue. The right anterior abdomen was included in the field of radiation. Twenty-four dogs (six/group) received fast neutrons with an average energy of 15 MeV to total doses of 1000, 1500, 2250 or 3375 rad in four fractions per week for six weeks. Fifteen dogs received 3000, 4500 or 6750 rad of photons (five/group) in an identical fractionation pattern. All neutron irradiated dogs receiving 3375 and 2250 rad and one receiving 1500 rad developed clinical signs of pancreatic, hepatic and gastrointestinal disturbances. The liver enzymes of these dogs became elevated and they died or were euthanatized in extremis 47-367 days after irradiation. Only one 6750 rad photon dog developed similar signs and died 708 days post-irradiation. Five neutron and 10 photon exposed dogs died of other causes. Neutron-induced lesions in the stomach and duodenum included hemorrhages, erosions, ulcerations and fibrosis. Ulcers perforated the GI tract of five dogs. Pancreatic lesions included degranulation and necrosis of acinar cells, fibrosis ans atrophy. Islet cells were not obviously damaged. All lesions were associated with degenerative and occlusive vascular changes. The RBE of fast neutrons, assessed by clinical signs, gross and microscopic pathology, is approximately 3-4.5 for pancreas and about 4.5 for pylorus and duodenum.

Animals↗
PubMed1984

Pleurectomy and intraoperative brachytherapy and postoperative radiation in the treatment of malignant pleural mesothelioma.

Forty-one patients with diffuse, pleural mesothelioma limited to one hemi-thorax underwent a thoracotomy at Memorial Sloan-Kettering Cancer Center from January 1976 to July 1982. Treatment at thoracotomy consisted of as complete a parietal pleurectomy as was possible to remove the bulk of the tumor. Measurable gross residual disease was treated whenever feasible, with permanent 125I implantation; residual diffuse disease was treated by a temporary 192Ir implantation or by postoperative instillation of 32P. External radiation therapy was given 4-6 weeks postoperatively to the involved hemi-thorax, shielding the lung and utilizing a combination of electron and a photon beam. A dose of 4500 rad in 4.5 weeks was given to the pleural surface by the mixed beam. There was no postoperative mortality in this group of 41 patients. Complications developed in 6 patients (15%). The median survival was 21 months; the one year survival was 65% and the two year survival was 40%. The median disease-free survival was 11 months and the one and two year disease-free survival 44 and 13% respectively. This study suggests that the combination of pleurectomy, intraoperative brachytherapy and postoperative external radiation increased the local control of the tumor and prolonged the survival.

Adult↗
PubMed1984

Dosimetry of rotational photon fields with gravity-oriented eye blocks.

Evolving radiotherapeutic technique is aimed at routine use of an eye protection accessory with uniformity of dose to facial tumors. Rotational 4 MV photon fields with gravity-oriented eye blocks are described in applications to patients and a phantom. A machine-oriented compensator with a slit and beveled edges at eye levels has been applied to increase uniformity of dose over the entire target, including partly blocked regions. Treatment planning parameters are derived from simple geometric relationships. Dose distributions and average tissue-air ratios (TAR) are calculated with a conventional radiotherapeutic treatment planning system, and measured during initial treatments via thermoluminescent dosemeters (TLD) in facial cavities. Machine monitor units of initial treatments (MU1) are calculated from prescribed dose D, TAR, percentage isodose lines, dose rates in air, and compensator transmission; for subsequent treatments, MU1 are modified using averages of unblocked target doses D measured during initial treatment: MU2 = (D/D)MU1. Doses measured on patients' eyelids have been 10 to 15% of prescribed dose. Three dimensional dose distributions were determined using TLD in an anthropomorphic phantom. With beam compensation, eye doses were 15% of unblocked target doses, doses to partly blocked target were 86 to 129% of unblocked target doses, and doses to unblocked target showed 5% mean standard deviations. In vivo and in phantom data were consistent with computer-calculated distributions. For uniformity of target dose, eye-sparing, and simplicity of irradiating tumors surrounding the eyes, the technique investigated compares favorably with conventional techniques.

Elementary Particles↗
PubMed1984

Pion treatment procedures and verification techniques.

Procedures and techniques developed for the negative pi-meson (pion) radiotherapy program at the Los Alamos Meson Physics Facility, Los Alamos, NM, are reviewed and described. A particular pion patient is followed through the entire planning and treatment sequence to describe CT scanning procedures, bolus and collimator and treatment techniques developed to minimize positioning errors (less than 5 mm). Comparison of 2-D and 3-D isodose calculations developed at Los Alamos showed differences of less than 10% attributable to multiple scattering effects and the computational models used. Treatment verification methods using in vivo ion chamber dosimetry generally confirmed the prescribed dose delivery within 10% and using TLD within 18%.

Elementary Particles↗