The influence of hyperbaric oxygen therapy and irradiation on hydroxyapatite ocular implant exposure and fibrovascular ingrowth in New Zealand white rabbits.

PURPOSE: Lack of adequate fibrovascular ingrowth has been implicated as a cause of exposure of hydroxyapatite (HA) implants in anophthalmic sockets. We investigated the vasculopathic effects of external beam irradiation, and the fibrovascular-enhancement effects of hyperbaric oxygen (HBO), on HA implant exposure and fibrovascular ingrowth in a rabbit model. METHODS: Eighteen rabbits underwent enucleation with implantation of a 12-mm HA sphere. Six rabbits received 20 Gy of external beam orbital irradiation prior to enucleation. Three irradiated and 6 nonirradiated rabbits received postoperative HBO. Three weeks postoperatively, all rabbits were evaluated clinically for evidence of implant exposure. Implants were then removed, and histopathologic analysis of fibrovascular ingrowth was performed. RESULTS: The amount of vascularization as measured by the depth of ingrowth was greater for nonirradiated (89% ingrowth) than for irradiated (71% ingrowth) animals. HA implant exposure occurred in 1 of 12 (8%) of the nonirradiated, and 4 of 6 (67%) of the irradiated rabbit orbits. HBO did not protect irradiated rabbits from exposure, but did enhance fibrovascular ingrowth in nonirradiated rabbits (100% ingrowth vs. 77% ingrowth). CONCLUSION: Impaired orbital vascularization from prior irradiation appears to retard fibrovascular ingrowth into HA implants, and is associated with an increased incidence of exposure. While HBO did not diminish the likelihood of exposure in irradiated sockets, HA fibrovascular ingrowth in normal orbits appeared to increase with HBO. This may have beneficial clinical application in cases of exposure in nonirradiated orbits.

Post-mastectomy radiotherapy following adjuvant chemotherapy and autologous bone marrow transplantation for breast cancer patients with greater than or equal to 10 positive axillary lymph nodes. Cancer and Leukemia Group B.

Between 2/87 and 2/91, 49 women with operable breast cancer involving greater than or equal to 10 axillary nodes were treated following mastectomy, with four cycles of Cyclophosphamide, Adriamycin, 5FU, followed by high doses of Cyclophosphamide, Cisplatin, Carmustine (HDCT) with autologous bone marrow transplant support. Forty patients received local-regional radiotherapy (generally to the chest wall, internal mammary, supraclavicular, +/- axillary nodal areas; minimum 44-50 Gy, 1.8-2 Gy/fraction, +/- 10-15 Gy scar boost; standard radiation techniques). The first nine patients did not receive local-regional radiotherapy. Three developed a local-regional failure (6-12 months after HDCT); six are without evidence of disease. Local-regional radiotherapy (LR XRT) was delivered to the subsequent 40 patients following HDCT+autologous bone marrow transplant. Six received less than 44 Gy of the planned local-regional radiotherapy due to significant toxicity and one of these failed locally. Only one local failure was observed among the 34 patients who received greater than or equal to 44 Gy. Two additional patients developed distant metastases. None of these 40 patients have failed in the axilla despite the fact that the axilla was irradiated in only 18 cases. Overall, 36/40 (90%) of these patients are without evidence of disease 4-30 months following HDCT (approximately 10-36 months after mastectomy, median 22 months). Radiotherapy was interrupted or discontinued because of progressive dyspnea, thrombocytopenia, or neutropenia in nine patients. Further studies to determine the roles of local-regional radiotherapy and HDCT in the development of these toxicities are underway. These encouraging results suggest that HDCT + autologous bone marrow transplant+local-regional radiotherapy may improve the survival rate in these high risk patients. A national randomized study to test the efficacy of this HDCT regimen is currently underway (Cancer and Leukemia Group B#9082 and Southwest Oncology Group #9114).

Effects of hyperthermia and irradiation on the growth of mouse melanoma tumors following immunotherapy.

Recent investigations suggest that adjuvant hyperthermia enhances the response of human malignant melanoma to ionizing radiation. A study was undertaken to explore the effect of radiation and hyperthermia on the responsiveness of melanoma following active immunization with lethally irradiated B16 melanoma cells in C57 BL 6 mice. Two groups of mice were treated: group 1 received immunotherapy on days 2-5 following tumor inoculation, and group 2 received immunotherapy on days 15-18 following tumor inoculation. The mice in each group were subsequently randomized into one of three subgroups: 1) no further treatment; 2) radiation therapy alone (6 Gy in a single fraction); 3) radiation therapy and regional hyperthermia (43 degrees C x 1 hour). Tumor sizes were measured regularly, and between day 52 and 63 the animals were sacrificed and the lungs sectioned for counting of metastatic tumors. Results from this study show that the immunomodulated B16 murine melanoma is responsive to radiation therapy alone and that this responsiveness is enhanced by the addition of adjuvant regional hyperthermia. There did not appear to be any significant effect of radiation therapy or radiation therapy plus hyperthermia on the development of lung metastases in this tumor model system.

The Duke AFM Program. Intensive induction chemotherapy for metastatic breast cancer.

Forty-five patients have completed treatment with AFM, an intensive induction chemotherapy regimen composed of Adriamycin (doxorubicin, Adria Laboratories, Columbus, Ohio), 5-fluorouracil, and methotrexate with folinic acid rescue. This regimen was designed to produce rapid and extensive tumor shrinkage prior to high-dose alkylating agent chemotherapy with autologous marrow support. The overall response rate was 91%, and 38% of patients achieved complete clinical responses after a mean of 70 days on treatment. Hematologic and mucosal toxicity were extensive, but no toxic deaths were noted. AFM is a potent remission induction regimen for metastatic breast cancer, but its considerable toxicity suggests caution in its use for routine breast cancer treatment.

Ophthalmic applications of biofeedback.

Biofeedback therapy has been shown to be of value in the treatment of numerous psychological and physiological problems. In this paper, applications of biofeedback for correction of oculomotor abnormalities including strabismus, nystagmus and amblyopia, refractive error correction, reduction of intraocular pressure (IOP), and blepharospasm suppression are reviewed.