Radiation therapy salvage of Hodgkin's disease following chemotherapy failure.

PURPOSE: This study evaluates the efficacy of comprehensive salvage radiation therapy, with or without chemotherapy, in selected patients with Hodgkin's disease who have failed primary combination chemotherapy. METHODS AND MATERIALS: Between 1972 and 1991, 28 patients with advanced Hodgkin's disease failing intensive combination chemotherapy in previously unirradiated nodal and/or pulmonary sites were treated with salvage radiotherapy with curative intent. Treatment consisted of comprehensive extended field radiotherapy to all known areas of disease. Total radiation doses ranged from 17.0 to 50.0 Gy, with only five patients (18%) receiving < 30.0 Gy to any field. Twelve patients also received chemotherapy as part of their salvage regimen. RESULTS: Twenty-six patients (93%) achieved a complete response and 14 (50%) remain in continuous complete remission at 14 to 133 months. In addition, three patients (11%) who failed salvage radiotherapy are now without evidence of disease following additional therapy. With a median follow-up of 47 months (range 14+ to 198+), actuarial median relapse-free survival and overall survival are 46 and 97 months, respectively. Actuarial 5-year relapse-free survival and overall survival are 40% and 63%, respectively. Patients with an initial complete response to chemotherapy had a significantly longer actuarial relapse-free survival than those with an initial partial response (p = 0.02). Salvage therapy was generally well-tolerated and resulted in no treatment-related deaths. CONCLUSION: Comprehensive salvage radiotherapy is of significant benefit in selected patients and should be considered an option for patients with advanced Hodgkin's disease following chemotherapy failure.

Interstitial thermoradiotherapy with ferromagnetic implants for locally advanced and recurrent neoplasms.

PURPOSE: The University of Arizona, University of California at San Francisco, City of Hope Medical Center, and University of Wisconsin participated in a Phase I/II protocol to assess the heating ability and the toxicity of interstitial thermoradiotherapy using ferromagnetic implantation. METHODS AND MATERIALS: Forty-four patients with advanced primary or recurrent extra-cranial solid malignancies were enrolled in this study. Fourteen gauge catheters were implanted into tumors and, once in the department of Radiation Oncology, loaded with ferromagnetic seeds to deliver a 60 min hyperthermia treatment. Multi-point thermometry was continuously used throughout the heating sessions for all patients, sampling the periphery as well as the core of the tumor. After 192Iridium brachytherapy, 18 patients then had an additional treatment. The mean radiation dose while on protocol was 50.0 Gy, with total doses (including prior radiotherapy) ranging from 20.3-151.8 Gy (median = 88.7 Gy). Response and toxicity were assessed by inspection, palpation, and/or radiologic studies. Forty-one patients were evaluable for response, and there were 55 analyzable hyperthermia treatment sessions. RESULTS: The complete response rate was 61% (25/41). The partial response rate was 31.7% and only 7.3% failed to respond. Median duration of local control has not yet been reached. The mean maximum, minimum, and mean time-averaged temperatures for all in-tissue sensors were 43.7 degrees C, 38.7 degrees C, and 41.0 degrees C, respectively. Tumor size was the only factor significantly correlated with temperatures or with complete response rate; larger tumors attained higher temperatures but smaller tumors had a higher response probability. Nineteen patients (43%) experienced toxicities, however there was only a 7% (3/44) rate of serious complications (Grade 3 or 4). Prior treatment with hyperthermia was the only factor significantly correlated with serious toxicity. CONCLUSION: These results, a 93% total response with only 7% serious toxicity, are encouraging especially in the context of the patient population treated. Phase II/III studies involving ferromagnetic implantation are warranted.

Radiation therapy for the palliation of multiple myeloma.

PURPOSE: This reviews the experience at the University of Arizona in an effort to define the minimum effective radiation dose for durable pain relief in the majority of patients with symptomatic multiple myeloma. METHODS AND MATERIALS: The records of 101 patients with multiple myeloma irradiated for palliation at the University of Arizona between 1975 and 1990 were reviewed. Three hundred sixteen sites were treated. Ten sites were asymptomatic, including six hemibody fields with advanced disease unresponsive to chemotherapy and four local fields with impending pathological fractures. Three hundred six evaluable symptomatic sites remained. The most common symptom was bone pain. Other symptoms included neurological impairment and a palpable mass. RESULTS: Total tumor dose ranged from 3.0 to 60 Gy, with a mean of 25 Gy. Symptom relief was obtained in 297 of 306 evaluable symptomatic sites (97%). Complete relief of symptoms was obtained in 26% and partial relief in 71%. Symptom relief was obtained in 92% of sites receiving a total dose less than 10 Gy (n = 13) and 98% of sites receiving 10 Gy or more (n = 293). No dose-response could be demonstrated. The likelihood of symptom relief was not influenced by the location of the lesion or the use of concurrent chemotherapy. Of the 297 responding sites, 6% (n = 19) relapsed after a median symptom-free interval of 16 months. Neither the probability of relapse nor the time to relapse was related to the radiation dose. Retreatment of relapsing sites provided effective palliation in all cases. CONCLUSION: Radiation therapy is effective in palliating local symptoms in multiple myeloma. A total dose of 10 Gy should provide durable symptom relief in the majority of patients.

Prostate tumor cell invasion: a comparison of orthotopic and ectopic models.

Interest in orthotopic models has been generated by recent reports of increased invasive and metastatic potential demonstrated by tumor cell lines following injection into their tissue of origin rather than subcutaneously. We have previously demonstrated that transfection of the tumorigenic human prostate cell line, Du-145, with the metalloproteinase matrilysin increased its ability to invade the diaphragm following an intraperitoneal injection. In this study we compare the invasive and metastatic behavior of transfected Du-145 cell lines injected into the dorsal lateral lobe of the prostate to that observed when they are injected intraperitoneally. Immunohistochemistry was used to examine 37 orthotopically injected severe combined immunodeficient mice for local invasion and metastatic lesions. In addition, the effect of injection site on the level of expression of four genes thought to influence the invasiveness of tumor cells (matrilysin, stromelysin, TIMP-1, and TIMP-2), was determined by northern analysis of orthotopic and subcutaneous tumor tissue. The results demonstrate that the level of mRNA expression of the genes examined was similar at the two sites of injection and that the invasive properties of Du-145 cells following orthotopic implantation were comparable to that observed on the diaphragm following intraperitoneal injection. The advantages of the diaphragm invasion model are: less procedure-related mortality, ease of cell delivery, and provision of an easily orientated structure in which the earliest penetration of a basal lamina can be observed.