Background: Experimental and clinical evidence suggest that hypoxia in solid tumours reduces their sensitivity to conventional treatment modalities modulating response to ionizing radiation or chemotherapeutic agents. The aim of the present study was to show the feasibility of determining radiotherapeutically relevant hypoxia and early tumour response by ([ 18 F] Fluoromisonidazole (FMISO) and [ 18 F]-2-fluoro-2'-deoxyglucose (FDG) PET.
Summarizing the FMISO uptake represents a global value for macroscopic tumor parts. As a noninvasive measurement this method seems highly feasible to evaluate the state of oxygenation in subjacent tumors.
These results support the hypothesis that tumour hypoxia has an effect on glucose metabolism. However, other factors affecting FDG uptake may be more predominant in chronic hypoxia, and thus FDG PET cannot reliably differentiate hypoxic from normoxic tumours.
There is controversy whether simultaneous thyrostatic medication influences the outcome of radioiodine (131I) therapy in Graves' disease by reducing the absorbed energy dose of 131I when delivering a standard dose. We therefore sought to ascertain whether the outcome of ablative 131I therapy is in any way affected by simultaneous thyrostasis (carbimazole) by aiming for a constant absorbed dose of 200-250 Gy. We prospectively studied 207 patients with Graves' disease (106 with and 101 without simultaneous carbimazole at the time of 131I therapy). All patients were reexamined 3, 6, and 12 months after 131I therapy. The 101 nonthyrostatic patients showed a highly significantly greater success rate (93%) than the 106 thyrostatic patients (49%). Stepwise logistic regression demonstrated that failure was related to the administration of carbimazole during 131I therapy (P < 0.00005) and the absorbed dose (P < 0.025), but was not related to free T3, free T4, TSH receptor antibodies, or thyroid volume. The success rate was 100% in 93 nonthyrostatic patients with absorbed doses of 200 Gy or more, but was only 12.5% (1 of 8) for absorbed doses less than 200 Gy. Correlation between success and absorbed dose was significantly higher for nonthyrostatic than for thyrostatic patients (r = 0.93 vs. r = 0.24). Sixteen patients who discontinued thyrostasis 1-3 days before 131I therapy showed 94% successes. Simultaneous thyrostasis is the decisive factor against a successful 131I therapy even if the significantly reduced 131I uptake/half-life values under thyrostasis are compensated with a higher delivered dose to ensure a comparable absorbed dose, possibly due to the additionally effective radioprotective properties of carbimazole. Therefore, if clinically feasible, we recommend discontinuing thyrostasis at least 1 day before beginning 131I therapy, because even in hyperthyroid nonthyrostatic patients the success rate was 100%.
Summary:We investigated the predictive value of sequential FDG PET before and after high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) in 24 patients suffering from non-Hodgkin's lymphoma (NHL). FDG PET was performed at baseline, after three cycles of induction therapy, before and after HDT with ASCT. Response assessment from sequential PET scans using standardized uptake values (SUV) was available in 22 patients at the time of transplantation. Partial metabolic response (PMR) was defined as a Ͻ25% decrease of SUV between successive PET scans. Six of seven patients who did not achieve a PMR after complete induction therapy developed lymphoma progression, while 10 of 15 patients with complete metabolic response (CMR) or PMR remained in continuous remission. Four of seven patients with less than PMR after induction therapy died vs two of 15 patients with CMR/PMR. Median progression-free and overall survival of patients with less than PMR after HDT and ASCT was 9 and 29 months, respectively. In contrast, neither conventional re-staging nor the International Prognostic Index were predictive. These data suggest that sequential quantitative PET imaging does enlarge the concept of chemosensitivity used to select patients with high-risk NHL for HDT and ASCT or to route them to alternative treatments. High-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) has been shown to be the best available treatment in patients who have relapsed from nonHodgkin's lymphoma (NHL) after conventional chemotherapy, but who remained chemotherapy-sensitive.1 This has prompted the use of HDT with ASCT as a front-line therapy in patients with high-intermediate or high risk disease according to the International Prognostic Index.2 However, clinical results have been discrepant and additional prognostic factors are needed to predict final outcome of the patients at the time of transplantation.Positron emission tomography (PET) using the glucose analogue fluorine-18-fluorodeoxglucose (FDG) has been demonstrated to improve primary staging of lymphoma and to be more precise than conventional radiological imaging for re-staging after chemotherapy.3-7 Several groups including our own have reported the high predictive value of persisting abnormal FDG uptake for residual or recurrent disease in this context.
7-9Thus FDG-PET does have a potential role in the identification of patients requiring further intensified chemotherapy. Moreover, FDG-PET can be used as a functional and quantitative measure of tumor response to induction chemotherapy 10 and may be able to differentiate between responders and non-responders at an earlier time-point than conventional CT or MRI imaging. Preliminary results in a small patient population studied before onset of treatment and again after one and two chemotherapy cycles support this hypothesis.
11We prospectively enrolled consecutive patients with NHL who were scheduled for HDT including ASCT. Progression-free and overall survival were chosen as end points of the study....
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