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Biomedical subjects

M M Kligerman

Publications and source records attributed to M M Kligerman.

At least 55 records · Page 3Linked to original sources
PubMed1980

Tissue reaction & tumor response with negative pi mesons.

As a prelude to a randomized trial of negative pi meson (pion) radiotherapy, as compared to conventional radiation treatment, tolerance of several normal tissues was investigated. Fifty-three of 108 patients received at least 2700 peak pion rads at a usual dose rate between 100 and 125 rads daily. The major sites treated were head and neck, pancreas, prostate, rectum and brain. Acute normal tissue reactions, late effects, and tumor response are correlated with the two dose levels. Pancreatic tumors have not fared well. At this point, tumors that can be observed disappear more rapidly, and, for tumors that cannot be observed, symptoms disappear more rapidly and normal tissues exhibit less reaction than with conventional radiotherapy. It is believed that the dose level can be raised an additional 7 percent above the current 4100 rads, measured at the maximum within the treatment volume.

Elementary Particles↗
PubMed1979

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↗
PubMed1979

Potential for therapeutic gain similar to pions by daily combinations of neutrons and low-LET radiations.

Biological studies with negative pi mesons (pions) at the Los Alamos Meson Physics Facility (LAMPF) have shown a relatively constant reduction of shoulder of the survival curve for single cell cultures and relatively constant reduction in the no response region for multicellular tumor spheroids (MTS) with little change in sensitivity (or slope), in both single dose and fractionated experiments. In clinical studies, a trend toward therapeutic gain for pions has been demonstrated in patients treated at LAMPF, with marked, rapid turmor regression for relatively mild acute normal tissue injury and no untoward effects observed over 7 to 24 months. Since the pion beams used therapeutically at LAMPF are characterized by a small amount of high-linear-energy-transfer (LET) radiation (in the range 10 to 20%), it is hypothesized that pion radiation as compared to x-rays increased the differential tolerance to sublethal injury in favor of normal tissues, resulting in therapeutic gain. It is further proposed that the near simultaneous application of high-LET radiation (such as neutrons) and low-LET radiation (such as x-rays) might create a bilogical situation similar to that of pion treatment, potentially resulting in therapeutic gain, although without the added benefit of dose localization obtainable with pions.

Animals↗
PubMed1979

Comparative late effects of X-rays and negative pimesons on the mouse kidney.

A system is described for comparing various modalities and fractionation schedules of radiation by means of their long-term morphologic effects upon the mouse kidney. The comparison system utilizes a grading scale for histopathologic changes in which a given histologic grade depends upon meeting defined threshold criteria, rather than quantitation of a particular measurement. Renal tubular alterations served as the basis for comparison, since they appeared more reliably defined than glomerular changes. The radiation dose that induced a specific threshold effect in kidneys from 50% of the animals at 6 months was defined as the effective dose-50%, or ED50.ED50 was found for x-rays and negative pimesons administered in 1, 2, or 5 fractions. From these data, the relative biologic effectiveness (RBE) of negative pi-mesons with respect to x-rays was determined for each fractionation schedule.

Animals↗
PubMed1978

Dose outside the treatment volume for irradiation with negative pions.

Irradiation of humans with negative pions requires a knowledge of the absorbed dose and radiation quality outside the primary pion beam. In conjunction with early clinical trials at LAMPF, experimental data have been obtained with microdosimetric techniques and multiwire proportional counters. Theoretical calculations have been made for the neutron contribution to the dose and are consistent with these data. Measurements were made with in 40 cm x 51 cm x 76 cm water phantom for a negative pion beam of initial momentum of 170 MeV/c, deltap = +/- 3MeV/c. The absorbed dose outside the treatment volume is the result of: (1) neutrons and photons from the pion interactions,(2) treatment room background and (3) peripheral muons, electrons and pions in the primary beam. The first two components are nearly isotropic and are congruent to 0.02% of the peak dose at a distance of 24 cm from the treatment volume; the third component is anisotropic and varies from 0.01 to 0.1% of the peak dose. Collimation of the bean increases the dose outside the treatment volume typically by 50%.

Elementary Particles↗
PubMed1977

Radiotherapy and rectal cancer.

Studies utilizing preoperative radiotherapy as an adjunct to surgery are reviewed, with results indicating marked increase in survival. Results of postoperative irradiation also appear beneficial, although less extensive data are available. Irradiation for inoperable and recurrent rectal cancer has demonstrated symptomatic relief, particularly avoidance of colostomy, and can render some patients operable and resectable. Adjuvant immunotherapy after irradiation and operation is suggested for further research.

Clinical Trials as Topic↗
PubMed1977

Current status of clinical pion radiotherapy.

An RBE for acute skin reaction to peak pions, for a specific fractionation scheme, has been established at 1.40-1.44. The time of development of acute skin reactions varied in 2 patients with 30 metastatic skin nodules treated with doses varying from 1,175 to 1,951 peak pions and 2,350 to 3,901 rads of 100 kVp x rays. The reactions reached their peak approximately one week apart at all dose levels with both forms of radiation. No untoward effects have been seen in epidermis or subcutaneous tissues as late as 169 days after the start of treatment. All nodules disappeared and have not returned 169 days after treatment. There is a strong suggestion that the response of thick tumors is sensitive to the proportion of high LET radiation deposited at various levels in the tumor.

Dose-Response Relationship, Radiation↗
PubMed1976

Initial comparative response to peak pions and x-rays of normal skin and underlying tissue surrounding superficial metastatic nodules.

Given the limitations of available material and methods for measuring skin response, the relative biological effectivenss (RBE) for the development and healing of skin reaction to pions in this experiment is 1.43. This is based on data obtained from a patient with malignant melanoma, in whom multiple skin nodules and the surrounding normal skin were randomized into three dose levels for pions and x-rays. The RBE for skin reaction was obtained while the skin tumor nodules appeared to regress at least as rapidly with pion therapy as with x-rays. Without benefit of adequate observation of time required for nodule regrowth, any estimate of tumor RBE is speculative.

Dose-Response Relationship, Radiation↗
PubMed1976

Radiation therapy for rectal carcinoma.

Rectal adenocarcinoma is a radiosensitive tumor. Radiation therapy can be safely given with acceptable tolerance during treatment. In clinically operable patients, this pretreatment appears to increase long-term survival by 43% or better. In symptomatic patients with primary inoperable recurrent disease, control of complants is possible in more than 80% of the patients, and colostomy is avoided in many. Finally, selected patients with inoperable cancer because of limited spread or nonresectable cancer, can be rendered operable by aggressive but tolerable pretreatment with supervoltage radiation. The possibility of long-term survival of such "bad" cases could possibly be enhanced.

Adenocarcinoma↗
PubMed1975

Preoperative radiation theration therapy in rectal cancer.

This paper outlines progress being made in the use of preoperative irradiation as an adjunct to surgery in the management of cancer of the rectum and rectosigmoid. Studies have shown that the normal rectal mucosa has a marked capacity for repair during fractionated radiation treatments. There is evidence that the use of preoperative irradiation reduces the number of involved lymph nodes found at operation. No marked interference with the ability of the surgeon to perform an abdominal perineal resection has been observed. In patients who subsequently undergo such a procedure, there are some data indicating that longevity may be increased when surgery is supplemented with preoperative irradiation, although further comparative studies are needed. Two studies are now under way by national clinical investigative groups.

Adenocarcinoma↗
PubMed1975

Biomedical program leading to therapeutic trials on pion radiation at Los Alamos.

Hypoxia and variations in cell cycle phase protect tumor cells being treated with x rays or gamma rays (cobalt). Heavy particles can overcome these protective effects, because of the dense ionization they deposit in tissues. Pions (negative pi mesons) can be directed to and stopped in a specific area, where they are captured by the nuclei of atoms, rendering the nuclei unstable. The nuclei disintegrate, releasing densely ionizing radiation. By confining the dense ionization to the tumor-bearing volume, pions have the potential of increasing the tolerance of the area under treatment to radiation, thus increasing the probability of destroying the tumor. A special channel at the proton factory at the Los Alamos Scientific Laboratory is producing pions for biomedical research. Considerable physical dosimetry has been completed. Cellular studies are underway to provide depth-dose-biological-effect curves. Animal studies will provide information on acute and late effects, which will permit the safe application of pions to a series of anatomical sites established by protocols for radiotherapy clinical trials.

Animals↗