Oscar A. Mendiondo

Relative biological effectiveness of modulated proton beams in various murine tissues

The relative biological effectiveness (RBE) of proton beams produced by Harvard University 160 MeV synchrocyclotron was studied in various murine tissues. Reference radiation was Cobalt-60 gamma-rays from a teletherapy unit at the Massachusetts General Hospital. Animals were C3Hf/Sed mice derived from our defined flora mouse colony. Test tissues are: lens, lung, testes and tail vertebrae. The RBE of the third generation isotransplants of a spontaneous mouse mammary carcinoma was also investigated. The proton and Cobalt-60 irradiations were carried out simultaneously by 2 teams. The dose response curves obtained for testes weight loss and growth stunting of tail vertebrae indicated that the RBE for our protons was independent of radiation dose in the range of 0.4 to 16 Gy. This finding was identical to our previous studies of the murine fibrosarcoma, skin and small intestine. The RBE values for lens and lung tissues were obtained by determining radiation dose to result in a complete cataract in half the irradiated eyes in 210 days and a 50% mortality in 180 days respectively. We have studied proton RBE in 7 normal tissues and 2 tumors including previously reported results. The RBE values for these tissues were found to fall between 1.09 and 1.32. No significant differences in the proton RBE were found between the several normal and tumor tissues studied.

Relative biological effectiveness of a high energy modulated proton beam using a spontaneous murine tumor In vivo

Abstract The relative biological effectiveness (RBE) for proton beams produced by 160 MeV Harvard University synchrocyclotron was studied in C3Hf/Sed mouse fibrosarcoma (FSa-II). Reference radiation was Cobalt-60 γ-ray. Cell survival was determined by 2 types of lung colony assays. Type A assays involved irradiation of solid tumors followed by immediate preparation of single cell suspension and the intravenous injection of the suspension. In type B assays, intravenous injection of single cell suspension, prepared from non-treated tumors, was followed by mouse thorax irradiation. The type B assay was used to determine survival of aerobic cells while the type A assay was used to analyze the survival of acutely hypoxic cells. Tumors were irradiated with 1 to 10 doses in the center of spread-out Bragg peak (SOBP) or in an incident plateau area. Survival curves were analyzed by alpha-beta (linear quadratic) model and RBE was determined at various survival levels. The RBE in SOBP was found to be independent of fraction size although 2 % of the proton beam was reported to be a result of high linear energy transfer (LET) events of greater than 100 KeV/μ. The RBEs at survival levels of 0.5, 0.1, and 0.01 were 1.16 ± 0.12, 1.16 ± 0.06 and 1.17 ± 0.05 respectively. The RBE in the incident plateau was not significantly different from that in SOBP.

Endobronchial brachytherapy in the treatment of recurrent bronchogenic carcinoma.

Abstract Local recurrence of lung cancer after high dose irradiation poses a difficult management problem. Three patients have been treated at the University of Kentucky Medical Center and Veterans Administration Hospital, Lexington, Kentucky with a combination of low dose external irradiation and endobronchial brachytherapy with satisfactory palliative results. Simple techniques for transbronchoscopic implantation or insertion of afterloading tubes are described.

A precision repeat localization head frame for fractionated stereotactic radiotherapy

An immobilization device was constructed for Fractionated Stereotactic Radiotherapy (FSRT) based on registration of the teeth and facial bones in a single thermoplastic mask system, along with a custom hardened foam pillow for posterior head immobilization relative to the mask. The unit interfaces mechanically with all of our current radiosurgery equipment and can be used with any standard stereotactic planning system. After initial trials to design a reproducible radiographic localization test, we performed a series of daily AP and Lateral port films on 3 patients over five isocenters. Seventy-nine films were reviewed and the maximum deviation in anatomical projection in both sagittal and coronal planes was less than 2 mm, with over 60% of films showing no distinguishable deviations from initial port films. Ninety-three percent of the test films showed a repositioning accuracy of less than 1 mm for all tested structures. We have developed an accurate, non-invasive means of repeat head immobilization that, when properly constructed, can facilitate precise fractionated stereotactic radiation therapy with patient comfort, ease of construction and long term stability.

A clinical trial for advanced cervico-vaginal pelvic carcinomas using californium CF-252 fast neutron therapy: Report of early responses☆

Abstract This report summarizes clinical experiences with Californium (Cf) 252 for the radiotherapy of advanced cervicovaginal carcinomas at the University of Kentucky Medical Center from November 1976 to April 1979. Fifty-nine patients were treated with Cf-252 during this period. After pilot studies, a treatment schedule was developed which appeared to offer improved local control and clearance of these tumors in ∼90% of treated patients. However, a longer follow-up period is essential to determine whether local tumor control is sustained or whether local tumor recurrence remains as great a problem as for patients who receive conventional radio-nuclide therapy. Ultimate long term survival and outcome will depend upon the frequency of control of local-regional disease and the frequency of appearance of more disseminated and metastatic disease. Cf-252 neutron brachytherapy was combined with 4500–5500 rad of Cobalt 60 or linear accelerator external beam fractionated radiotherapy for 4–6 weeks. Neutron treated patients whose disease was in appropriate clinical stages were also treated with combined radiotherapy-surgery without problems. Stage dependent regression was noted; low stage tumors responded distinctly better and more rapidly than higher stage tumors. All histological patterns responded, and no unusual severe or unanticipated early side effects or toxic tissue reactions were observed.

Complications associated with preoperative radiation therapy and iodine-125 brachytherapy for localized prostatic carcinoma

Twenty-five consecutive patients with localized adenocarcinoma of the prostate treated with 1,050 rad preoperative radiation therapy and Iodine-125 seed brachytherapy arreviewed. Significant long-term postoperative complications included radiation cystitis (12%), radiation proctitis (4%), genital and leg edema (12%), stress incontinence (8%), total incontinence (4%), and impotence (26%). Complications occurred in 75 per cent of patients who received additional postoperative radiation. Improved staging with CT scan, lymphangiography, and Chiba needle biopsy of any possibly abnormal lymph nodes provided excellent preoperative staging with only 1 patient (6%) upstaged at surgery to Stage D1.

TOXICITY AND RADIATION PROTECTIVE EFFECT OF WR-77913 IN BALB/c MICE

The toxicity and radiation protective effect obtained by intraperitoneal injection of WR-77913 have been investigated in BALB/c mice. The toxic LD50/30 was 3574 mg/kg. When WR-77913 was given 30 min before whole body irradiation adequate protection was observed against bone marrow and gut death. Dose modifying factors of 1.91 and 1.76 for bone marrow and 1.95 and 1.80 for gut death were obtained with drug doses roughly equivalent to one half and one quarter of the maximum tolerable doses (MTD). No protective effect was observed against central nervous system injury. Preliminary experiments with the EMT6 tumor show limited tumor protection with a dose of WR-77913 equivalent to 70 per cent of the MTD. Because of its low toxicity, adequate bone marrow and gut protection at doses equivalent to one quarter MTD and limited protection of the EMT6 tumor, WR-77913 deserves further investigation to determine its value in multiple drug dose regimens and its capability to protect other normal tissues.

Afterloading interstitial radiation therapy

Abstract A technique for afterloadiug interstitial radiation therapy employing Angiocath- 192 Ir is hereby described. Its flexibility and applicability to various lesions arising from the skin, breast, lymph nodes and oral cavity is discussed. Four cases are presented to illustrate various points.

Concurrent and subsequent tumors in the same host: A model to evaluate the host tumor interaction

Abstract There is evidence which demonstrates an immune rejection response (IRR) directed against tumor cells in some experimental and human tumors. In the case of FSa-1, a methylcholanthrene-induced fibrosarcoma of the C 3 Hf/Sed mouse, the IRR is manifested by a decrease in the dose of radiation expected to control half of the treated tumors (TCD 50 ) and an increase in the number of tumor cells expected to transplant the tumor in half of the transplanted recipients (TD 50 ) in immunized hosts. FSaI was transplanted simultaneously in the right and left legs of male and female C 3 Hf/Sed mice and each tumor was given 3750 rad when it measured 8 mm. in diameter (viz the TCD 50 value for 8 mm FSaI growing as one isotransplant per animal). The two tumors in any one animal usually responded similarly with either permanent regression or local recurrence after irradiation. In a second experiment, a group of animals received also concurrent tumors. This time an immunogenic FSaI was transplanted in one side and a non immunogenic mammary carcinoma (MDAH-MCaIV) on the opposite side. The tumors were irradiated with TCD 50 doses (3750 rad for FSaI and 6500 for the less radioresponsive MCa). The distribution of local control and recurrence was probabilistic; 50% of the animals exhibited one tumor destroyed and one recurring. In a third experimental group mice were subsequently transplanted with FSaI Mice who showed no recurrence after irradiation of their first FSaI showed a stronger tendency to reject the second implantation than those who previously had local recurrence and subsequent amputation. Retransplants were controlled more easily by irradiation in the group that had been successfully treated for the first transplant. These data indicate that within the inbred population of C 3 Hf/Sed mice there is a relatively broad distribution of capacities to react effectively against the FSaI challenge. This was not predicted by the delayed hypersensitivity skin reaction (DHSR) to the FSaI antigen.

Lysozyme levels and macrophage content of tumor tissue in C3H mice bearing fibrosarcoma transplants treated by radiation and Corynebacterium parvum

Abstract Serum levels of lysozyme (SL) were measured in C3H mice bearing early generation isotransplants of a methylcholanthrene induced fibrosarcoma (FSa) and of a spontaneous mammary carcinoma (MCa). SL increased with growth of FSa beyond 1000 mm 3 ; in MCa mice, SL was independent of tumor volume. SL could not predict control probability for the FSa after treatment by irradiation or intravenous Corynebacterium parvum . The macrophage content of FSa decreased as tumors reached massive size; few macrophages were found in FSa growing in immunosuppressed hosts and in MCa in normal hosts. The administration of C. parvum did not substantially increase the macrophage infiltration of either FSa or MCa. The concentration of lysozyme per unit tumor volume increased slightly with progressive growth of the FSa, was low in FSa in immunosuppressed hosts and increased slightly in FSa mice given C. parvum . Macrophage content and TL of 8 mm diameter FSa did not predict control probability after treatment with irradiation or C. parvum. Moderate differences in macrophage content of immunogenic FSa may reflect degrees of efficiency of host response, but such differences are insufficient to serve as prognostic indicators. Macrophage content of tumors and TL may be of value in identifying weakly immunogenic tumors or hosts which mount only a feeble response.