Ionizing irradiation is a well-established therapeutic modality for cancer. Photodynamic therapy (PDT), especially with 5-ALA and Photofrin, is highly effective in some tumor types. Chemical modifiers, so-called radiosensitizers, are used in order to increase the efficacy of radiotherapy. Most of the known and routinely used radiosensitizers are not tumor selective, so that the normal tissue reaction toxicity is also increased. In the present study we investigated whether a porphyrin derivative that is currently used as a tumor-photosensitizing agent in photodynamic therapy (PDT) may also act as a tumor-specific radiosensitizer.For our investigation we used Balb/c mice implanted with Lewis sarcoma and irradiated with 3 Gy combined with injection of 5-ALA or Photofrin at various concentrations before irradiation.5-ALA had no effect as a radiosensitizer at any of the concentrations examined. Photofrin at a concentration of 5 mg/kg proved to be a chemical modifier of ionizing radiation, delaying tumor growth and reducing the overall tumor volume by about 50% after six days.Photofrin has marked efficacy as a radiosensitizer and can be used in the future as a selective tumor radiosensitizer.
Pituitary metastases are found in about 1% of all pituitary resections. They often derive from breast, lung, and gastroenteric tract adenocarcinomas, very rarely from thyroid carcinoma. Presenting symptoms of thyroid carcinoma metastatic to the pituitary gland are usually chiasmatic with central neurological impairment due to space-occupying expansion in the parasellar region. Hypopituitarism is more often associated with papillary and medullary rather than follicular thyroid carcinoma (FTC). Here we describe a patient with pituitary metastasis from FTC who had hypopituitarism with thyrotropin (TSH) deficiency.A 61-year-old woman, who presented with visual deficits and pain to the right orbit, was found on magnetic resonance imaging to have a large mass involving the pituitary gland. She was found to have pituitary insufficiency based on corticotropin-releasing hormone and TSH-releasing hormone testing. Transnasopharyngeal biopsy of the mass revealed metastases from FTC. After total thyroidectomy, which confirmed widely invasive FTC, the patient underwent external beam radiation therapy of the metastases for progressive neurological symptoms and an increase in orbit pain. Since endogenous TSH production was insufficient, we used recombinant human TSH (rhTSH) as preparation for a series of radioiodine treatments. rhTSH administration, followed by 7.4 GBq of (131)I, was repeated seven times over a 10-year period. This was associated with a marked decrease in serum thyroglobulin levels accompanied by substantial clinical improvement, but after 7 years disease progression occurred.Seven patients with pituitary metastases from FTC have been reported. In all cases, some neurological signs and symptoms related to mass effect were reported, but no pituitary insufficiency was described. This may be the first case of FTC with metastases to the pituitary causing hypopituitarism. It seems likely that management of such cases could be limited to biopsy to confirm thyroid carcinoma, rather than more extensive surgery, and that this could be followed by multiple treatments with rhTSH followed by (131)I.
Background. Attempting to optimize treatment results in pediatric Hodgkin disease while minimizing major side effects, at least in early-stage patients, in 1983 the Italian Association of Pediatric Hematology and Oncology (AIEOP) conceived a multicenter study tailored according to stage, bulky mediastinal mass, and age. Methods. Between December, 1983 and January, 1989, 215 evaluable patients (median age, 9.9 years, range, 1–15 years) received the AIEOP-MH 1983 Hodgkin disease protocol of low-dose radiation therapy (20–25 Gy), with three cycles of adriamycin, bleomycin, vinblastine, and imidazole carboxamide (ABVD) for children with early-stage and favorable disease, and with alternating cycles of an eight non-cross-resistant drug combination regimen (nitrogen mustard, vincristine, procarbazine, and prednisone [MOPP]/ABVD) for 6 months for those with bulky and unfavorable disease. Patients in advanced stages received four additional courses of MOPP/ABVD as maintenance therapy. Results. The overall survival and freedom from progression (FFP) probabilities at 7 years are 85.7% and 81.5% respectively. FFP probabilities at 7 years in Groups 1 (58 patients in Stages I and IIA with mass/thorax [M/T] < 0.33), 2 (56 patients in Stages IIA, IB, IIA with M/T > 0.33, IIB, and IIIA), and 3 (38 patients in Stages IIIB and IVA and B) were 94.8%, 81.4%, and 60.3%, respectively. Multivariate analysis showed B symptoms, M/T > 0.33, and stage to be significant, independent prognostic factors affecting survival and FFP curves. Conclusions. The encouraging results in early-stage disease indicate the validity of using less toxic treatment in this subgroup to maximize quality of life. Patients with bulky mediastinal disease tended to fare worse than those with M/T < 0.33 or without mediastinal involvement (FFP at 7 years: 69.4% versus 93.3%) and showed early local recurrence. In advanced stages, the eight-drug combination regimen (MOPP/ABVD) plus low-dose radiation therapy provided no major improvement in outcome; here, alternative chemotherapeutic regimens should be tested in a large, randomized, clinical trial to evaluate their efficacy and determine the frequency of delayed toxicity.
