Homayoon Shidnia

Carcinoma of major salivary glands

Ninety‐four patients with carcinoma of the major salivary glands seen at Indiana University Hospitals from 1960–1977 were studied. Eighty‐four patients completed their planned course of therapy, and 49 of 84 patients remain alive with no evidence of disease 2–17 years following treatment. Comparison has been made for three modalities: surgery alone, radiation therapy alone, and a combined approach. Surgery alone was used for treatment of early lesions, and 22 of 38 patients (58%) remain free of disease. Radiation therapy alone was used for advanced cases and palliation, and 6 of 16 patients (37.5%) remain free of disease. In the combination treatment, 21 of 30 patients (70%) are alive and free of disease from 2–17 years after treatment. Ten patients did not complete treatment and all of these patients died of disease. Cancer 45:693‐697, 1980.

The Clinical and Radiographic Aspects of Radiation Osteitis

Patients with radiation osteitis were studied in regard to the protean manifestations of this entity as it affects the skeleton, with emphasis on distinguishing radiation osteitis from radiation osteogenic sarcoma, metastatic bony involvement, or simple changes of disuse. Bone fragmentation, resorption, and soft tissue calcification may mimic the appearance of a radiation-induced osteogenic sarcoma. In the absence of infectious or traumatic complications, an area of known radiation osteitis which suddenly changes in appearance, becomes symptomatic, or is associated with a mass lesion should be considered neoplastic.

Preliminary clinical results of combined 433 megahertz microwave therapy and radiation therapy on patients with advanced cancer

Seventy patients with far‐advanced histologically proven malignancies were treated with a combination of microwave irradiation (433.92 MHz) and ionizing radiation. Of the twenty‐one patients who completed the planned course of treatments and are eligible for a minimum of nine‐month follow‐up, 90% experienced complete relief of symptoms and 10% received partial relief of symptoms. Complete regression of all localized tumor occurred in sixteen of the twenty patients (80%), and nine of the complete responders remain free of disease from nine to fourteen months. It was the opinion of the clinicians involved in this study that the heat administered by the microwave unit potentiated the effects of ionizing radiation over those which would have been seen if radiation were used alone. In view of the fact that all patients in this study had cancers which were previously considered to be refractory to further medical treatment, the marked relief of symptoms and tumor response to combined therapy were encouraging. This preliminary study confirms the impression that the effects of radiation are enhanced by heat and forms the basis for a randomized series involving far‐advanced but previously untreated head and neck and gynecological malignancies. Cancer 40:2854‐2863, 1977.

Influence of elevated temperature on natural killer cell activity, lymphokine-activated killer cell activity and lectin-dependent cytotoxicity of human umbilical cord blood and adult blood cells

PURPOSE To determine whether hyperthermia is to the benefit or detriment of host immune function, the effect of hyperthermia was evaluated on various functions of T-lymphocytes from human umbilical cord blood and compared to that of adult blood. METHODS AND MATERIALS Nonadherent mononuclear cells from cord blood or adult blood were used as the effector cells. To generate lymphokine activated killer (LAK) cells, effector cells were kept in culture for 5 days in complete medium containing recombinant human interleukin-2. To activate effector cells to become cytotoxic, cells were kept in culture in complete medium containing Con A. Cytotoxicity was determined in a standard 4-h chromium release assay using K-562 human erythroleukemic cells (in the natural killer cell activity assay) or Daudi cells (in the LAK cell activity or Lectin dependent cytotoxicity assay) as targets. For heat effects, cells in complete medium were heated at the desired temperature in a water bath for 1 h. RESULTS Lymphokine-activated killer cell activity, lectin-dependent cytotoxicity and T-cell proliferative capacity were not deficient in human cord blood. Cytotoxic activities of T-cells from adult blood as well as from cord blood can be enhanced at febrile range (< or = 40 degrees C), and were significantly decreased by exposure to 1 h at 42 degrees C. CONCLUSION The febrile responses (< or = 40 degrees C) to infection, in the course of malignant disease and with biological response modifiers treatment, may all be related to host defense mechanisms. Based on these observations, whole body hyperthermia (< or = 40 degrees C), in combination with the appropriate cytokines, may have therapeutic potential in the treatment of neonatal infections and malignancies under certain circumstances. Hyperthermia in febrile range may, therefore, confer an important immunoregulatory advantage to the host. In contrast, tumor killing therapeutic temperature (> 42 degrees C) which inhibits host immunocompetence should probably be used only for local hyperthermia.

Oat cell carcinoma of the lung. Early treatment results of combination radiation therapy and chemotherapy.

Since August 1974, 50 patients with histologically proven oat cell carcinoma of the lung were treated at Indiana University Hospitals with a combination of adriamycin, cyclophosphamide, Oncovin, BCG immunotherapy, and radiation therapy to the primary lung tumor and whole brain. Twenty‐nine patients are eligible for a 6‐month follow‐up and are included in this report. All 29 patients responded to therapy; 12 patients (41%) had a minimum of 50% reduction in tumor mass and 17 patients (59%) had complete clinical remission of disease. Eight (38%) of the 29 patients have remained in complete remission from 6 to 14 months, and 90% of the patients survived a minimum of 6 months. This represents a considerable improvement in survival rates over what had been obtained at Indiana University Hospitals previously.

Advanced stage IIIB cancer of the cervix treatment by hyperthermia and radiation.

Treatment records of patients with primary untreated Stage IIIB carcinoma of the cervix treated at Indiana University Department of Radiation Oncology from November 1964 through January 1979 were reviewed. During this period, 79 patients were treated; 46 received external therapy using cobalt-60, 15 received a 25-MV photon beam, and 18 received a 25-MV photon beam followed by 45 min of 434-MHz microwave hyperthermia producing central tumor core temperatures of 39.5 to 41.5 degrees C. All patients received similar doses of radiation using combination intracavitary radioactive isotopes and external therapy. Patients who received heat therapy in combination with radiation therapy did not have increased acute or chronic complications of normal tissues. Local tumor control was superior when regional heat therapy was given; however, long-term absolute survival rates were not affected as the survival rate at 5 years was not statistically different in any of the three treatment groups.

Radiation and Microwave Therapy in the Treatment of Advanced Cancer

Seventy-two patients with advanced cancer were treated with combinations of heat and radiation in two groups: (a) heat + radiation, and (b) radiation + heat. Of those treated with heat prior to radiation therapy, 32/60 (53%) experienced complete remission of symptoms. In the group exposed to heat after radiotherapy, 11/12 patients (92%) achieved complete remission. The authors present two cases and a review of the literature.

Whole body hyperthermia: A potent radioprotector in vivo

Interleukin-1 has been reported to be an effective radioprotective agent in mice subjected to lethal doses of irradiation. Production of Interleukin-1 can be increased by whole body hyperthermia. Therefore, whole body hyperthermia was assessed for its efficacy in protecting the lethal effects of ionizing radiation in DBA/2 mice. One hour of 40 degrees C +/- 0.2 whole body hyperthermia given 20 hr before 900 cGy total body irradiation protected 100% of DBA/2 mice from an LD 100/16 radiation dose (dose of irradiation that killed 100% of the mice in 16 days). Lethal doses of total body irradiation produced profound monocytopenia, decreased cellularity of thymus, spleen, and bone marrow, and suppressed Interleukin-1 production. Interleukin-1 production was determined using the thymocyte proliferation assay. Whole body hyperthermia accelerated recovery of blood leukocytes by up to 5 days post-total body irradiation in DBA/2 mice. Thymocytes, spleen, and bone marrow cells were activated by whole body hyperthermia, as assessed by the cells response to Concanavalin A. This was accompanied by accelerated Interleukin-1 generation. Our results provide the first evidence that whole body hyperthermia acts as a potent radioprotector in vivo, effects that may be mediated by Interleukin-1.

Whole-body hyperthermia decreases lung metastases in lung tumor-bearing mice, possibly via a mechanism involving natural killer cells

The effects of whole-body hyperthermia (WBH) on the course of the Lewis lung carcinoma (LLC) and B16 melanoma (B16) were examined. WBH was generated by microwave (2450 MHz) at an intraperitoneal temperature of 39.5–40.0°C and an intratumoral temperature of 40.0–40.5°C for 30 min once a week, ×3 (LLC) or ×6 (B16). The mice were sacrificed 21 days (LLC) or 42 days (B16) after tumor implantation and lung metastases were scored. Natural killer (NK)-cell activity was determined against the YAC-1 tumor target in WBH-treated tumorbearing mice as well as in tumor-bearing mice but untreated controls. The number of lung metastases was significantly reduced and NK-cell activity was higher in animals treated with WBH. Thus, this study suggests that WBH interferes with the spread of organ metastases, possibly through a mechanism involving NK cells.

Treatment results of retinoblastoma at indiana university hospitals

This paper summarizes a review of all cases (70) of retinoblastoma seen at Indiana University Hospitals over the past 25 years (from 1952 to 1977) to determine the results of treatment and causes of failure. All cases from July, 1967, to the present were managed by the same group of physicians, thus following a consistent philosophy of treatment for those patients. Thirty‐two patients treated during this latter period have survived a minimum of two years and are alive. Visual acuity of 20/20 has been preserved in all 16 patients with unilateral disease and a range of 20/50 to 20/20 in 12 of the 16 patients with bilateral disease. Because of the highly specialized diagnostic and therapeutic techniques and equipment required for optimal treatment results, it is recommended that patients with retinoblastomas be referred to treatment centers specializing in the management of this disease. Cancer 40:2917‐2922, 1977.