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Explorotory study of proton radiation therapy using large field techniques and fractionated dose schedules.

Three patients have been treated with 160-MeV protons combined with high-energy photons to examine the advantages and difficulties associated with the clinical implementation of a program of large-field, fractionated-dose, protonradiation therapy. We havefound it necessary to 1) obtain an accurate three-dimensional determination of the treatment volume including the density of all tissues in the beam path; 2) construct an adequate bolus to compensate for tissue heterogeneities; 3) use much more precise and accurate immobilization and patient positioning devices than used in photon irradiation; 4) treat with both protons and photons so as to keep the skin dose within an acceptable level. IN TISSUES WITHOUT SIGNIFICANT INHOMOGENETIES DUE TO BONE AND AIR SPACES WE HAVE DELIVEREDA WELL-DEFINED DOSE TO INVOLVED TISSUES WHILE SPARING DISTAL SENSITIVE STRUCTURES. However, in those regions where there is much "fine structure" of tissue density, it has been difficult to compensate satisfactorily for the inhomogeneties.

Adult↗

High-energy photon and electron beam.

The optimum radiation treatment plan for any given clinical situation can be achieved by combining various irradiation modalities and beam energies. The availability of equipment that provides photon and electron beams of energies from 4 MeV to 25 MeV permits optimal dose distribution throughout the treatment volume. Since no difference in the biological effectiveness of electrons compared with megavoltage photons has been demonstrated in laboratory studies, there is no hesitation in combining electrons with photons. The selection of the various energies, the combination of electrons with photons, and the ratio of the given doses of each beam depend on the location of the tumor and the maximum depth to be treated. With the use of one beam alone, a combination of 25 MeV and 4 to 6 MeV photon beams, or a combination of photons and electrons, the most effective treatment plan with the available beams can be designed for any clinical situation.

Adult↗

Experience with pion radiotherapy.

Forty-one patients with a total of 86 tumors were treated with negative pimesons (pions) at the Los Alamos Meson Physics Facility (LAMPF) through December 31, 1977. An additional 30 tumors in the total patient population were treated with 100 kVp x-rays to assess comparative effects on skin nodules and 8 patients received additive photon or electron radiation to pion-treated portals. Of 52 evaluable tumors in 20 patients treated with pions only and followed for 3 to 22 months, 81% (42 tumors) completely regressed; 6% (3 tumors) partially regressed; and 13% (7 tumors) did not respond, although 5 of the 7 have shown no growth for 10 months. Of eight tumors in seven patients treated with a combination of pions and conventional radiation, three tumors showed complete response and five tumors showed partial response, though the resected specimens in two (one with complete and one with partial response) revealed no tumor microscopically. Reactions in normal tissues have been mild, with some patients exhibiting no normal tissue reaction, as compared with relatively marked tumor response.

Abdominal Neoplasms↗

Radiotherapy for Kaposi's sarcoma.

Between 1954 and 1976, 60 patients with Kaposi's sarcoma were treated in the Department of Radiotherapy of the Lahey Clinic Foundation at the High Voltage Research Laboratory of Massachusetts Institute of Technology. Only 2 patients were free of clinical disease in the lower extremities at the time of initial presentation, and 40 patients (69%) had cutaneous lesions involving areas extending above the knees. Eight patients (13%) also presented with mucous membrane involvement in addition to skin disease. Twenty-one patients were treated only with megavoltage electrons during the initial course of radiotherapy, and 12 patients were treated with supervoltage photons alone. The remaining 27 patients were treated with a combination of electrons and photons; in 17 patients, the same tumor sites were irradiated with both modalities. Eleven patients received whole-body surface electron irradiation. The choice of treatment modalities was based on the extent and distribution of cutaneous disease and depth of the lesions. The overall response rate was 93% after a single fractionated course of radiotherapy. Twenty-five patients achieved complete regression and 18 were in remission for 2-13 years. Response rates were also analyzed with respect to the three subgroups in terms of treatment modalities. A single dose of 800 to 1200 rads or its equivalent was required to control local cutaneous lesions. Widespread visceral metastasis was the most common cause of failure and death; the incidence of second malignancies was increased. Trial of systemic chemotherapy and immunotherapy would seem to be a reasonable therapeutic adjunct.

Adult↗

Phase I pilot study on fast neutron teletherapy for advanced carcinomas of the head and neck region. Final report on local control rate and survival.

A final report is presented on the local control rate and length of survival for 100 patients with advanced squamous cell carcinomas of the head and neck region who received fast neutron teletherapy at the University of Washington during the period 1973 through 1977. Sixty-two patients were treated with neutrons alone and 38 were treated with a combination of neutrons and photons as part of a mixed beam fractionation scheme. The overall initial complete remission rate was 68% for the mixed beam group and 44% for the group treated with neutrons alone. Initial complete remission rates for the two groups of patients are given as a function of T-stage and N-stage and acturarial curves are presented which show the time course of local control and survival for the two treatment groups. For T3 and T4 lesions the initial complete remission rate appears to be greater using the mixed beam form of treatment than using neutrons alone. Treatment to high-dose levels using neutrons alone gave rise to significantly greater morbidity--both acute and late effects--than resulted from the mixed beam form of treatment. Local control rates and survival rates are compared with similar groups of patients treated with neutrons at other institutions.

Adult↗

Preliminary results of a Phase I/II study with pi-meson (pion) treatment for bladder cancer.

Radiation therapy with negative pi-mesons (pions) was administered to 36 patients with bladder cancer. According to a Phase I/II study, doses varied from 3000 to 3600 pion rad. Although only two complete responses were achieved among 8 evaluable patients who had predominantly papillary bladder tumors, more promising results were obtained in 22 evaluable patients who had sessile, invasive carcinomas: 19 bladders were cystoscopically and cytologically cleared of tumor after 6 months. Although the side effects during the ambulatory treatment were minimal or tolerable, a steep dose-response curve for late side effects was observed with severe complications in 7 of 11 patients who received 3600 or more pion rad.

Adenocarcinoma↗

Aneurysm clips: evaluation of magnetic field interactions with an 8.0 T MR system.

This study was conducted to evaluate magnetic field interactions for aneurysm clips exposed to an 8.0 T magnetic resonance (MR) system. Twenty-six different aneurysm clips were tested for magnetic field translational attraction (deflection angle test) and torque (qualitative assessment method) using previously described techniques. Six of the specific aneurysm clips (i.e. type, model, blade length) made from stainless steel alloy (Perneczky) and Phynox (Yasargil, models FE 748 and FE 750) displayed deflection angles above 45 degrees and torque measurements of +4, indicating that these aneurysm clips maybe unsafe for patients or individuals in an 8.0 T MR environment. The specific aneurysm clips (i.e. type, model, blade length) made from commercially pure titanium (Spetzler), Elgiloy (Sugita), titanium alloy (Yasargil, model FE 750T), and MP35N (Sundt) displayed deflection angles less than 45 degrees and torque that ranged from + 1 to +4. Accordingly, these aneurysm clips are likely to be safe for patients or individuals exposed to an 8.0 T MR system. Depending on the actual dimensions and mass, an aneurysm clip made from Elgiloy may or may not be acceptable for a patient or individual in the 8.0 T MR environment.

Electromagnetic Fields↗

Pi meson radiotherapy for advanced head and neck neoplasms: preliminary results.

Under the auspices of the University of New Mexico Cancer Research and Treatment Center, trials are under way at the Los Alamos Meson Physics Facility to evaluate the effects of pi meson irradiation on locally advanced human tumors. This paper summarizes the preliminary results in patients with locally advanced head and neck tumors treated under Phase 1 and Phase II studies. A total of 26 patients were treated between June 1977 and May 1979 with a minimum follow-up of 9 months and a maximum follow-up of 33 months. Sites of disease included the oropharynx in 10 cases (base of tongue in 7, tonsil in 2, and pharyngoepiglottic fold in 1), the supraglottic larynx in 4, the nasopharynx in 5, the oral cavity in 4, the hypopharynx in 2, and the sublingual salivary gland in 1. Twelve of the 26 patients are alive, and 10 survive with no evidence of disease. Doses employed ranged from a minimum of 1,000 peak pion rad in 7 fractions over 9 days to a maximum of 5,4000 peak pion rad in 51 fractions of 89 days. The minimum dose employed for any patients treated with peak pions alone was 3,000 rad. These data are analyzed according to dose, sit, histology, tumor response, local control, and survival. Results from these cases form the basis of the Phase III randomized trials for advanced squamous-cell carcinomas of the head and neck, which are currently in progress.

Carcinoma↗

Structure-activity studies using valence molecular connectivity.

The extension of the molecular connectivity concept to the treatment of heteroatom molecules affords an opportunity to examine structure-activity relationships in a wide variety of molecule series that possess biological activity. Four series are described in this report. The correlations found indicate that molecular connectivity is an extremely useful descriptor of structure in studying drug molecule structure-activity relationships.

Aniline Compounds↗

The contribution of the physical sciences to the development of radiation therapy.

Radiation therapy is used in the treatment of about half of all cancer patients in the United States. The development of this specialty has been intimately involved with major advances in the physical sciences, from the discovery of x-rays by Roentgen and radium by the Curies, to the technological breakthroughs of World War II that led to the 60cobalt teletherapy unit and the modern linear accelerator--the principal treatment machines in use today. These historical events are described and the principal characters introduced.

Elementary Particles↗

Negative ion fragmentations of deprotonated peptides: backbone cleavages directed through both Asp and Glu.

The collision-induced spectra of [M - H](-) ions of a variety of natural and synthetic amphibian peptides containing Asp and/or Glu exhibit characteristic gamma backbone cleavage ions that identify the positions of these residues in the peptide. A theoretical study suggests that the Glu cleavage involves an S(N)i reaction of the carboxylate anion from the Glu alpha side chain to form a deprotonated cyclic lactone. The presence of either Asp or Glu or other residues that effect pronounced side-chain cleavages (e.g. Ser or Thr) results in the normal alpha and beta backbone cleavages being reduced in comparison to those cleavages which originate from side chains.

Amino Acid Sequence↗

Aggregation of Silver Hydrosols Prepared in Air.

The chemistry involved in the preparation and activation of silver hydrosols was monitored by pH, potential, and surface charge measurements, by absorption spectra in the visible region, and by surface-enhanced Raman spectroscopy (SERS). The activation, displayed by a red-shift of the colloid absorption at 392 nm, corresponds to a partial aggregation of elementary silver particles as displayed by transmission electron micrographs. The participation of carbonate species in the chemistry of hydrosols handled in air was made obvious by titration with strong acids. The colloid destabilization was performed either with protons, by adding strong non-complexing acids (HNO3, HClO4), or with low concentrations of Cu2+. In contrast, HCl determined a stabilization of hydrosols related to the complexing affinity of Cl- toward silver. The successive addition of Cu(NO3)2 and HCl allowed a balance between all the chemical reactions and a very efficient activation process. Whereas the chemical reactants used are nominally inorganic, at total concentrations lower than 10(-3) M, the activated hydrosols display anomalous SER spectra which were previously assigned to organic molecules. Copyright 1998 Academic Press.

Journal Article↗

Meson radiobiology and therapy.

High-linear energy transfer radiation (neutrons, heavy ions, and pions) have a greater relative biological effectiveness than low-linear energy transfer radiation by depositing a high density of ionization in irradiated cells. This overcomes the protective effect of oxygen; decreases the variation in sensitivity among the several stages of the cell cycles; and, inhibits the repair of sublethal damage as compared to x-rays, gamma rays, electrons and protons. Negative pi mesons (pions), appear particularly suited for radiation therapy as their penetration and depth-dose profile lend themselves to shaping the high dose area to the tumor size and location. Preliminary biological experiments with pions produced at the Los Alamos Meson Physics Facility studied cell survival at various radiation depths and cell cycle sensitivity. Histologic study of data from the first human experiments indicated severe tumor cell destruction by pions as compared to x-rays in treating malignant melanoma skin nodules, without increased effects on dermal elements.

Dose-Response Relationship, Radiation↗