Mapping Bone Marrow Response in the Vertebral Column by Positron Emission Tomography Following Radiotherapy and Erlotinib Therapy of Lung Cancer (original) (raw)
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Radiotherapy and Oncology, 2012
Objectives: The objectives were (i) to confirm that diagnostic FDG-PET images could be obtained during thoracic radiotherapy, (ii) to verify that significant changes in FDG uptake or volume could be measured early enough to adapt the radiotherapy plan and (iii) to determine an optimal time window during the radiotherapy course to acquire a single FDG-PET examination that would be representative of tumour response. Methods: Ten non-small cell lung carcinoma (NSCLC) patients with significant PET/CT-FDG tumour radioactivity uptake (versus the background level), candidates for curative radiotherapy (RT, n = 4; 60-70 Gy, 2 Gray per fraction, 5 fractions per week) or RT plus chemotherapy (CT-RT, n = 6), were prospectively evaluated. Using a Siemens Biograph, 5 or 6 PET/CT scans (PET n , n = 0-5) were performed for each patient. Each acquisition included a 15-min thoracic PET with respiratory gating (RG) 60 ± 5 min post-injection of the FDG (3.5 MBq/kg), followed by a standard, 5-min non-gated (STD) thoracic PET. PET 0 was performed before the first RT fraction. During RT, PET 1-5 were performed every 7 fractions, i.e., at 14 Gy total dose increment. FDG uptake was measured as the variation of SUV max,PETn versus SUV max,PET0 . Each lesions' volume was measured by (i) visual delineation by an experienced nuclear physician, (ii) 40% SUV-⇑ Corresponding author. Address: (A. Edet-Sanson), bdubray@ rouen.fnclcc.fr (B. Dubray), shapdey@rouen.fnclcc.fr (S. Hapdey), rmodzelewski@ rouen.fnclcc.fr (R. Modzelewski), igardin@rouen.fnclcc.fr (I. Gardin), pierre.vera@ rouen.fnclcc.fr (P. Vera).
Molecular imaging and radionuclide therapy, 2011
A 64-year-old male patient with small cell lung cancer underwent Fluorine-18 fluorodeoxyglucose (F 18 FDG) positron emission tomography (PET)/CT scan which revealed multiple F 18 FDG uptake in the spine, both humeri, ribs, pelvis and proximal long bones. There was no obvious lytic or sclerotic bone destruction accompanying these lesions on CT component of the study. After the patient received six courses of chemotherapy a repeat F 18 FDG-PET/CT was performed for evaluation of therapy response. The PET/CT showed the presence of multiple sclerotic lesions on CT without FDG uptake, corresponding to the bone lesions on the previous PET/CT scan. A concomitant Tc 99m Methylene diphosphonate (Tc 99m MDP) bone scintigraphy (BS) revealed no pathologically increased Tc 99m MDP uptake in the skeletal system. The FDG avid lesions in the skeletal system, which were not sclerotic initially, were transformed into FDG non-avid sclerotic lesions after chemotherapy. This was attributed to the direct ...
Radiotherapy and Oncology, 2011
Objectives: To investigate the changes in tumour proliferation (using FLT), metabolism (using FDG), and hypoxia (using F-miso) during curative (chemo-) radiotherapy (RT) in patients with non-small-cell lung cancer (NSCLC). Patients and methods: Thirty PET scans were performed in five patients (4 males, 1 female) that had histological proof of NSCLC and were candidates for curative-intent RT. Three PET-CT (Biograph S16, Siemens) scans were performed before (t 0 ) and during (around dose 46 Gy, t 46 ) RT with minimal intervals of 48 h between each PET-CT scan. The tracers used were 18 fluoro-2deoxyglucose (FDG) for metabolism, 18 fluorothymidine (FLT) for proliferation, and 18 F-misonidasole (F-miso) for hypoxia. The 3 image sets obtained at each time point were co-registered (rigid: n = 9, elastic: n = 1, Leonardo, TrueD, Siemens) using FDG PET-CT as reference. VOIs were delineated (40% SUV max values were used as a threshold) for tumours and lymph nodes on FDG PET-CT, and they were automatically pasted on FLT and F-miso PET-CT images. ANOVA and correlation analyses were used for comparison of SUV max values. Results: Four tumours and twelve nodes were identified on initial FDG PET-CT images. FLT SUV max values were significantly lower (p < 0.0006) at t 46 in both tumours and nodes. The decrease in FDG SUV max values had a trend towards significance (p = 0.048). F-Miso SUV max values were significantly higher in tumours than in nodes (p = 0.02) and did not change during radiotherapy (p = 0.39). A significant correlation was observed between FLT and FDG uptake (r = 0.56, p < 10 À4 ) when all data were pooled together, and they remained similar when the before and during RT data were analysed separately. FDG and F-miso uptakes were significantly correlated (r = 0.59, p = 0.0004) when all data were analysed together. The best fit was obtained after adjusting for lesion type (tumour vs. node). This correlation was observed for the SUV max measured during RT (r = 0.70, p = 0.008) but not for the pre-RT data (r = 0.19, p = 0.35). The weak correlation between FLT and F-miso uptakes only became significant (r = 0.66, p = 0.002) when the analysis was restricted to the data acquired during RT. Conclusion: Three different PET acquisitions can be performed quasi-simultaneously (4-7 days) before and during radiotherapy in patients with NSCLC. Our results at 46 Gy suggest that a fast decrease in the proliferation of both tumours and nodes exists during radiotherapy with differences in metabolism (borderline significant decrease) and hypoxia (stable).
Journal of Cancer, 2015
The purposes of this study were: 1) to show bone marrow (BM) functional heterogeneity, 2) to demonstrate site-dependent responses of BM to cancer treatment utilizing whole body FDG-PET/CT and 3) to identify correlations between FDG uptake in different bone sites and long term complete blood count (CBC). Methods: Thirty two patients who had pre-and post-treatment FDG-PET/CT scans were selected retrospectively. Each patient received either head and neck radiation for cancer of the tongue, or pelvic radiation for rectal or cervical cancer with chemotherapy. Patients had FDG-PET/CT performed prior to the first radiation therapy session and at least one FDG-PET/CT after completion of the prescribed radiation therapy. Results: FDG uptake before radiotherapy was significantly different among bone regions (p < 0.01). This heterogeneity was felt to reflect site-dependent amounts of BM contents possibly due to structural and functional requirements. FDG uptake in the irradiated regions was significantly decreased on the first and second follow-ups after radiation. Feasibly, this could be due to a reduction in the number of active BM cells following intensive radiation in addition to concurrent chemotherapy. Overall, CBC significantly decreased after treatment. Correlation values of each hematological parameter with FDG uptake varied among skeletal regions and scan time points. FDG uptake in sacrum and lumbar regions had better correlation with white blood cells and neutrophils. Conclusions: Longitudinal FDG-PET revealed a regional functional heterogeneity of the BM site-dependent response to treatment. Patients experienced immediate and prolonged marrow metabolic damage that correlates with hematological parameters. FDG-PET/CT may provide additional capabilities to assess BM health.
Clinical and Translational Radiation Oncology
To investigate effects of radiotherapy (RT) and erlotinib on pulmonary glucose uptake using 2-deoxy-2-(18F)fluoro-D-glucose (18 F-FDG) positron emission tomography (PET) during and after treatment of non-small cell lung cancer (NSCLC) and to identify associations between serum cytokine levels and lung glucose uptake. Material and methods: Twenty-seven patients with advanced NSCLC, receiving RT alone or concomitant RT and erlotinib therapy, were examined by 18 F-FDG PET before, during, and after treatment. A total of 57 18 F-FDG PET scans were analyzed. Pulmonary 18 F-FDG uptake and radiotherapy dose mapping were used to acquire dose-response curves for each patient, where subsequent linear regression gave a glucose uptake level in the un-irradiated parts of the lungs (SUV 0) and a response slope (DSUV). Serum cytokine levels at corresponding time points were assessed using a multiplex bioassay. Correlations between the most robust cytokines and lung 18 F-FDG dose response parameters were further investigated. Results: From the dose response analysis, SUV 0 at post-therapy was significantly higher (P < 0.001) than at mid-and pre-therapy (45% and 58%, respectively) for the group receiving RT + erlotinib. Also, SUV 0 at posttherapy was higher for patients receiving RT + erlotinib compared to RT alone (42%; P < 0.001). No differences in DSUV were seen with treatments or time. SUV 0 was positively associated (r = 0.47, P = 0.01) with serum levels of the chemokine CC motif ligand 21 (CCL21) for patients receiving RT + erlotinib. Conclusions: Concomitant RT and erlotinib causes an elevation in pulmonary 18 F-FDG uptake post treatment compared to RT alone. Pulmonary glucose uptake is associated with an upregulation of a chemokine (CCL21) involved in inflammatory reactions.
European Journal of Radiology, 2013
Purpose: To compare maximum and mean standardized uptake values (SUVmax/mean) of normal organ tissues derived from [ 18 F]-fluoro-desoxyglucose (FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) using MR attenuation correction (MRAC) (DIXON-based 4-segment -map) with [ 18 F]-FDG positron emission tomography/computed tomography (PET/CT) using CT-based attenuation correction (CTAC). Methods and materials: In 25 oncologic patients (15 men, 10 women; age 57 ± 13 years) after routine whole-body FDG-PET/CT (60 min after injection of 290 ± 40 MBq [ 18 F]-FDG) a whole-body PET/MRI was performed (Magnetom Biograph mMR TM , Siemens Healthcare, Erlangen, Germany). Volumes of interest of 1.0 cm 3 were drawn in 7 physiological organ sites in MRAC-PET and the corresponding CTAC-PET images manually. Spearman correlation coefficients were calculated to compare MRAC-and CTAC based SUV values; Wilcoxon-Matched-Pairs signed ranks test was performed to test for potential differences. Results: The mean delay between FDG-PET/CT and PET/MRI was 92 ± 18 min. Excellent correlations of SUV values were found for the heart muscle (SUVmax/mean: R = 0.97/0.97); reasonably good correlations were found for the liver (R = 0.65/0.72), bone marrow (R = 0.42/0.41) and the SUVmax of the psoas muscle (R = 0.41). For subcutaneous fat, the correlation coefficient was 0.66 for SUVmean (p < 0.05). Correlations between MRAC and CTAC were non-significant for SUVmean of the psoas muscle, SUVmax of subcutaneous fat, SUVmax and SUVmean of the lungs, SUVmax and SUVmean of the blood-pool. The median SUVmax and SUVmean in MRAC-PET were lower than the respective CTAC values in all organs (p < 0.05) but heart (SUVmax) and the bone marrow (SUVmean). Conclusion: In conclusion, in oncologic patients examined with PET/CT and PET/MRI SUVmax and SUVmean values generally correlate well in normal organ tissues, except the lung, subcutaneous fat and the blood pool. SUVmax and SUVmean derived from PET/MRI can be used reliably in clinical routine.
PURPOSE: To evaluate the predictive value of early and late residual (18)F-fluorodeoxyglucose (FDG) and (18)F-fluorothymidine (FLT) uptake using different SUV measurements in PET in patients with advanced non-small-cell lung cancer (NSCLC) treated with erlotinib. METHODS: We retrospectively reviewed data from 30 patients with untreated stage IV NSCLC who had undergone a combined FDG PET and FLT PET scan at 1 week (early) and 6 weeks (late) after the start of erlotinib treatment. Early and late residual FDG and FLT uptake were measured in up to five lesions per scan with different quantitative standardized uptake values (SUV(max), SUV(2Dpeak), SUV(3Dpeak), SUV(50), SUV(A50), SUV(A41)) and compared with short-term outcome (progression vs. nonprogression after 6 weeks of erlotinib treatment). Receiver-operating characteristics (ROC) curve analysis was used to determine the optimal cut-off value for detecting nonprogression after 6 weeks. Kaplan-Meier analysis and the log-rank test were used to evaluate the association between residual uptake and progression-free survival (PFS). RESULTS: Nonprogression after 6 weeks was associated with a significantly lower early and late residual FDG uptake, measured with different quantitative parameters. In contrast, nonprogression after 6 weeks was not associated with early and late residual FLT uptake. Furthermore, patients with a lower early residual FDG uptake measured in terms of SUV(max) and SUV(2Dpeak) had a significantly prolonged PFS (282 days vs. 118 days; p = 0.022) than patients with higher values. Similarly, lower late residual FDG uptake and early residual FLT uptake measured in terms of SUV(3Dpeak), SUV(A50) and SUV(A41), and late FLT uptake measured in terms of SUV(3Dpeak) and SUV(A50) was associated with an improved PFS. CONCLUSION: Early and late residual FDG uptake, measured using different quantitative SUV parameters, are predictive factors for short-term outcome in patients with advanced NSCLC treated with erlotinib. Additionally, low residual FDG and FLT uptake early and late in the course of erlotinib treatment is associated with improved PFS.
Nuclear medicine review. Central & Eastern Europe, 2019
Radiotherapy may result in long term effects and composition alterations in bones. Bone scintigraphy after radiotherapy may demonstrate decreased skeletal uptake; however, this is a transient effect with bone scan normalized after a few years. We describe a case of a 31-year-old female patient treated for left breast cancer with chemotherapy and radiotherapy, exhibiting reduced and diffuse diphosphonate uptake in the heavily irradiated sections of left ribs, even twelve years post-treatment. Similarly, quantitative computed tomography indicated altered bone composition. To our knowledge this is the first case describing such a long radiation side effect in breast cancer treatment.
According to the recommendations ofthe Dosimetry Task Group of the American Association of Physicists in Medicine, blood-derived estimates of the red marrow (RM) dose from radiolabeled monoclonal antibodies (MAbs) are valid only if the RM is devoid of any specific uptake. There is, therefore, a clear need for an alternative method for estimating the RM dose in patients receiving MAbs that target normal or abnormal (malig nant) bone marrow elements. Radiolabeled LL2, an anti-B-cell murine MAb, targets normal B cells and malignant lymphoma cells in the RM. This may result in an increased radiation dose to the RM through neigh boring targeted activity. We investigated whether imaging-based esti mates of the RM dose, particularly using sacral scintigraphy, correlate with myelotoxicity in non-Hodgkin's lymphoma patients who received ‘311-LL2. The sacrum-based RM dose (RMs) was estimated from sacral activity by assuming that 9.9% of the total adult RM is contained in the sacrum. The sacrum was not used if there was focally increased or decreased sacral uptake. Myelotoxicity was assessed based on Radiation Therapy Oncology Group criteria. Twelve of 21 non-Hodgldn's lym phoma patients treated had adequate imaging, dosimetry, and follow-up to evaluate myelotoxicity. Eight of these patients had diffusely increased RM uptake on their MAb scans. The average estimated RMs in the eight patients was 168 ±62 cGy (mean ±SD) with only 50 mCi ‘311-LL2. Six of these patients (75%) developed grade 3 or 4 myelotoxicity. In contrast, the average RMs in the four patients who did not have any enhanced uptake on their scans was 71 ±30 cGy (P < 0.02). None of these patients developed grade 3 or 4 toxicity. These results suggest that image-based estimates ofthe RM dose may be predictive ofmyelotoxicity and should be used in patients with diffuse RM uptake on their scans.