A stochastic model was developed to validate the results obtained with the mammaglobin-nested RT-PCR assay for tumor cell detection in peripheral blood of breast cancer patients. Since the assay consists of four PCR setups per peripheral blood sample, the probabilities for receiving 0, 1, 2, 3, or 4 positive setups were calculated. In this model, samples with just 500 mammaglobin mRNA molecules are highly probable to result in at least three positive setups, whereas lower quantities shift the probabilities towards one or two positive setups. In the clinical trial, samples with one or two mammaglobin positive setups were detected in 6/143 (4%) patients with benign lesions of the breast, in 41/310 (13%) breast cancer patients with no evidence of disease and in 39/157 (25%) breast cancer patients with metastatic disease. On the contrary, no sample from patients with benign lesions of the breast resulted in three or four positive setups, but 5/310 (2%) breast cancer patients with no evidence of disease and 46/157 (29%) with metastatic disease. These results correspond with the model: an increased number of tumor cells in peripheral blood lead to a higher amount of mammaglobin mRNA molecules, and these samples may result in at least three positive setups. Samples with three orfour positive setups were mainly derived from breast cancer patients with metastatic disease and only occasionally from patients with no evidence of disease. On account of these results, samples with at least three positive setups are of prognostic value and regarded as tumor cell positive.
associated with high response rates and decreased rates of neurotoxicity compared with higher dose WBRT. Our treatment policy for PCL patients with residual disease following chemotherapy is whole-brain irradiation to a total dose of 23.4 Gy in 13 fractions of 1.8 Gy followed by a sequential boost up to 45-50 Gy in 25 fractions of 1.8-2 Gy to the primary site/residual tumor. We propose a new methodology in order to limit the dose to the healthy brain to the prescribed dose by using composite planning (bias dose planning). Materials/Methods: We treated two patients with PCL and residual disease after chemotherapy using our methodology. First, we prepared a "standard plan", where the WBRT dose was planned first for volumetric arc therapy (VMAT) using the Monoco TPS (Elekta), followed by the sequential boost dose plan; second, a "bias plan" where the sequential boost dose was planned first, and only thereafter the WBRT dose using the bias dose planning option with the Monaco TPS in order to have a final composite plan corresponding to the prescribed doses. Results: Treatment plans resulting from bias dose planning had a markedly reduced dose to the brain outside of the boost. The mean dose to the brain minus the boost volume was of 25.00 Gy AE 0.5 Gy (Bias plan) vs 30.00 AE 0.6 Gy (standard plan). Conclusion: Composite planning of the boost first and only thereafter planning the dose to the brain taking the boost plan into account allows a reduction of 5 Gy to the healthy brain. To our knowledge, in lymphoma treatment, the total delivered dose is important, rather than the dose per fraction. We recommend this procedure for PCL radiations that have a sequential boost.
The case of an 11-year-old girl with mediastinal stage III B-E Hodgkin's disease is described. She achieved complete remission with combined chemoradiotherapy according to the Swiss Pediatric Oncology Group-HD Protocol 1985. Six months after all therapy was stopped, a slowly growing retrosternal mass was detected. Computed tomography (CT) and gallium-67 single-photon emission CT (SPECT) could not elucidate the true origin of the tumor, nor did ultrasound-guided transthoracic fine-needle puncture. Open biopsy with histologic examination of the lesion has successfully identified the mass as thymic hyperplasia, a rebound immunologic reaction after chemoradiotherapy that mimicked tumor regrowth.
Observations on 29 children with Hodgkin's disease confirm that the initial spread, presence or absence of general symptoms, and histological type all have prognostic significance. The results of lymphangiography in 27, and laparotomy with multiple biopsies and splenectomy in 14 children demonstrated that - except in stage IV - both procedures are necessary for adequate classification as to stage of the disease. On the basis of these personal cases (5-year-survival rate of 53%) and published reports a therapeutic schema is suggested which is particularly appropriate for children.
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