Hans S Poulsen

Copenhagen University Hospital, København, Capital Region, Denmark

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Publications (78)404.15 Total impact


  • No preview · Article · Nov 2015 · Neuro-Oncology

  • No preview · Article · Nov 2015 · Neuro-Oncology
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    Preview · Article · Nov 2015 · Neuro-Oncology
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    Preview · Article · Nov 2015 · Neuro-Oncology
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    Full-text · Article · Nov 2015 · Neuro-Oncology
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    Full-text · Article · Nov 2015 · Neuro-Oncology
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    ABSTRACT: Methods: uPAR mRNA expression analysis of tumors from 19 GBM patients was performed and a cell culture derived from one of these patients was used to establish an orthotopic GBM xenograft model. Tumor growth was monitored using bioluminescence imaging. Five to six weeks after inoculation, all mice were microPET/CT scanned with two new uPAR PET ligands ((64)Cu-NOTA-AE105 and (68)Ga-NOTA-AE105) and with (18)F-fluoroethyl-1-tyrosine (FET) for comparison. One MRI scan was performed in each mouse to confirm tumor location. The uPAR specificity of (64)Cu-NOTA-AE105 was confirmed by alignment of H&E and uPAR immunohistochemistry stained slides of the brain, with distribution of activity using autoradiography. Results: uPAR expression was found in all 19 GBM patient tumors investigated and high expression of uPAR correlated with decreased overall survival (P = 0.04). Radiolabeling of NOTA-AE105 with (64)Cu and (68)Ga was straightforward resulting in a specific activity of approximately 20 GBq/µmol and a radiochemical purity of >98% for (64)Cu-NOTA-AE105 and >97% for (68)Ga-NOTA-AE105. High image contrast, resulting in clear tumor delineation, was found for both (68)Ga-NOTA-AE105 and (64)Cu-NOTA-AE105. A higher absolute uptake of (18)F-FET in tumor (3.5±0.8 %ID/g) was observed compared to (64)Cu-NOTA-AE105 (1.2±0.4 %ID/g) and (68)Ga-NOTA-AE105 (0.4±0.1 %ID/g). Similar pattern was also observed in background brain tissue, where uptake of (18)F-FLT was 1.9±0.1 %ID/g, compared to (68)Ga-NOTA-AE105 (0.05±0.01 %ID/g) and (64)Cu-NOTA-AE105 (0.11±0.02 %ID/g). This resulted in a significantly higher tumor-to-background ratio for both (68)Ga-NOTA-AE105 (7.6±2.1, p< 0.05) and (64)Cu-NOTA-AE105 (10.6±2.3, p<0.01) compared with (18)F-FET-PET (1.8±0.3). Autoradiography of brain slides confirmed that the accumulation of (64)Cu-NOTA-AE105 corresponded well with uPAR positive cancer cells. Conclusion: Based on our translational study uPAR PET could be a highly promising new imaging biomarker for GBM. Further clinical explorations of uPAR PET in GBM are therefore justified.
    No preview · Article · Oct 2015 · Journal of Nuclear Medicine
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    ABSTRACT: Purpose: Both [(18)F]-fluoroethyltyrosine (FET) PET and blood volume (BV) MRI supplement routine T1-weighted contrast-enhanced MRI in gliomas, but whether the two modalities provide identical or complementary information is unresolved. The aims of the study were to investigate the feasibility of simultaneous structural MRI, BV MRI and FET PET of gliomas using an integrated PET/MRI scanner and to assess the spatial and quantitative agreement in tumour imaging between BV MRI and FET PET. Methods: A total of 32 glioma patients underwent a 20-min static simultaneous PET/MRI acquisition on a Siemens mMR system 20 min after injection of 200 MBq FET. The MRI protocol included standard structural MRI and dynamic susceptibility contrast (DSC) imaging for BV measurements. Maximal relative tumour FET uptake (TBRmax) and BV (rBVmax), and Dice coefficients were calculated to assess the quantitative and spatial congruence in the tumour volumes determined by FET PET, BV MRI and contrast-enhanced MRI. Results: FET volume and TBRmax were higher in BV-positive than in BV-negative scans, and both VOLBV and rBVmax were higher in FET-positive than in FET-negative scans. TBRmax and rBVmax were positively correlated (R (2) = 0.59, p < 0.001). FET and BV positivity were in agreement in only 26 of the 32 patients and in 42 of 63 lesions, and spatial congruence in the tumour volumes as assessed by the Dice coefficients was generally poor with median Dice coefficients exceeding 0.1 in less than half the patients positive on at least one modality for any pair of modalities. In 56 % of the patients susceptibility artefacts in DSC BV maps overlapped the tumour on MRI. Conclusion: The study demonstrated that although tumour volumes determined by BV MRI and FET PET were quantitatively correlated, their spatial congruence in a mixed population of treated glioma patients was generally poor, and the modalities did not provide the same information in this population of patients. Combined imaging of brain tumour metabolism and perfusion using hybrid PET/MR systems may provide complementary information on tumour biology, but the potential clinical value remains to be determined in future trials.
    No preview · Article · Sep 2015 · European Journal of Nuclear Medicine

  • No preview · Article · Aug 2015 · Cancer Research

  • No preview · Article · Aug 2015 · Cancer Research
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    ABSTRACT: The survival times of patients with glioblastoma differ widely and biomarkers that would enable individualized treatment are needed. The objective of this study was to measure changes in the vascular physiology of tumor using T1-dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in patients with glioblastoma during early stages of radio- and chemotherapy (Tx) and explore possible correlations with treatment outcomes. An exploratory prospective study was planned. Patients underwent DCE-MRI at baseline, after approximately one and six weeks of Tx and three and six months post-Tx. DCE-MRI at three Tesla generated maps of blood flow (BF), blood volume (BV), permeability (Ki) and volume of distribution (Vd) using a combination of model-free deconvolution and Patlak plots. Regions of interest in contrast enhancing tumor and in normal appearing white matter were contoured. Progression-free survival (PFS) was the primary clinical outcome. Patients with PFS > 6 months were compared with those with PFS < 6 months. Parameters of vascular physiology and changes in these during Tx were compared for these two groups at all time points using non-parametric statistics. Eleven eligible patients were included and 46 DCE-MRI examinations were carried out. BF in tumor increased for all patients early during Tx (p = 0.005) and then fell to a level below baseline at post-Tx examinations (p = 0.016). A similar but non-significant trend was seen for tumor BV. There was no detectable difference between patients with PFS > 6 months versus PFS < 6 months with regards to baseline values or changes during and after Tx. Although no correlations to outcomes were found, the results of this exploratory study may be hypothesis generating and will be examined in a larger patient group.
    Preview · Article · Jul 2015 · Acta oncologica (Stockholm, Sweden)
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    ABSTRACT: Small cell lung cancer (SCLC) is an aggressive disease with high mortality, and the identification of effective pharmacological strategies to target SCLC biology represents an urgent need. Using a high-throughput cellular screen of a diverse chemical library, we observe that SCLC is sensitive to transcription-targeting drugs, in particular to THZ1, a recently identified covalent inhibitor of cyclin-dependent kinase 7. We find that expression of super-enhancer-associated transcription factor genes, including MYC family proto-oncogenes and neuroendocrine lineage-specific factors, is highly vulnerability to THZ1 treatment. We propose that downregulation of these transcription factors contributes, in part, to SCLC sensitivity to transcriptional inhibitors and that THZ1 represents a prototype drug for tailored SCLC therapy. Copyright © 2014 Elsevier Inc. All rights reserved.
    Full-text · Article · Dec 2014 · Cancer Cell
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    ABSTRACT: BACKGROUND AND PURPOSE: Re-irradiation of HGG at recurrence may be a viable treatment option for some patients. Positron emission tomography (PET) using the amino acid tracer, 18F-fluoro-ethyltyrosine (FET) may have higher specificity and sensitivity than MRI in this setting. Both FET PET and MRI were used for target delineation in a prospective trial. The purpose of this study was to evaluate the impact of FET PET on the radiotherapy target. MATERIAL AND METHODS: A phase I trial examined the safety of hypofractionated stereotactic re-irradiation at different dose levels. Patients in PS 0-2 with localized recurrence of HGG and no other treatment options were eligible. With MRI, tumor was manually contoured using T1 contrast enhanced sequences. For PET, a threshold of 1.6x mean in background was used in a semi-automatic segmentation procedure. The planning target volume for treatment was the combination of both tumor volumes (MRI and PET) plus a 2 mm margin. Matlab software was used for spatial analyses. (Trial identifier: NCT02025231). RESULTS: Twenty-eight patients were included (GBM: n = 22; grade 3 glioma: n = 6). All patients had received radiotherapy and temozolomide, and 61 % had previously received bevacizumab. Median tumor volume defined by MRI and PET was 34 cm3 (range: 0-230 cm3) and 24 cm3 (range:0-214 cm3), respectively. Using PET increased the total gross tumor volume by a median of 10 cm3 (range:0-77 cm3), compared to MRI alone. The median longest distance from the MRI-target to encompass the PET-target was 10 mm (range: 0.6 to 43 mm). CONCLUSION: Tumor volumes defined by MRI and PET were spatially separated by up to 43 mm indicating that large portions of PET positive tumor would be missed if the target was solely based on MRI (T1 + contrast). FET PET may be useful for tumor delineation in re-irradiation of HGG.
    No preview · Article · Nov 2014 · Neuro-Oncology
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    ABSTRACT: BACKGROUND: The radiolabeled amino acid O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) and thymidine analog 3'-deoxy-3'-18F-fluorothimidine (18F-FLT) are widely used for positron emission tomography (PET) brain tumor imaging; however, results from comparative studies are scarce. Due to the limited transport of FLT across the intact blood-brain barrier (BBB) we hypothesize that anti-VEGF response assessment with FLT PET primarily reflects changes in the BBB, whereas FET PET is less affected by the tumor vasculature. The aim of this study was therefore to evaluate and compare the value of FLT and FET MicroPET for anti-VEGF response assessment in orthotopic human glioma xenografts. METHODS: Cells of human glioblasoma multiforme (GBM) neurosphere culture (NGBM_CPH048p6_LUC) were injected orthotopically in NMRI nude mice. At confirmed tumor take, mice were treated with anti-VEGF therapy (B20-4.1) or saline as control. Treatment response was followed by weekly bioluminescence, 18F-FLT and 18F-FET MicroPET/CT. The end-point was survival and brains from sacrificed mice were used for immunohistochemistry and subsequent quantification of the Ki67 proliferation index and micro-vessel density (MVD). RESULTS: The relative 18F-FET tumor-to-brain of (T/B) ratio of SUVmax was significantly decreased after one week (99 ± 6%, n = 6 vs. 124 ± 9%, n = 5; p = 0.04) and after two weeks (106 ± 10%, n = 5 vs. 156 ± 17%, n = 4; p = 0.03) in the B20-4.1 group as compared with the control group. However, with 18F-FLT MicroPET there was no significant difference in the T/B ratio of SUVmax neither after one week of treatment (134 ± 12%, n = 6 vs. 144 ± 6%, n = 6; p = 0.49) nor after two weeks of treatment (174 ± 11%, n = 5 vs. 208 ± 30%, n = 5; p = 0.34). We found a significant lower MVD in the B20-4.1 group as compared to the control group (66 ± 8%, n = 8 vs. 100 ± 10%, n = 7; p = 0.02). However, we found no difference in the Ki67 proliferation index in the treatment group as compared to the control group (18.9 ± 1%, n = 7 vs. 19.8 ± 2%; n = 6; p = 0.7). In addition, the median survival was not prolonged in the treatment group as compared to the control group (19 vs. 21 days, p = 0.34). CONCLUSION: In NGBM_CPH048p6_LUC xenografts B20-4.1 anti-VEGF treatment induced changes in the MVD and in 18F-FET uptake without affecting the Ki67 proliferation index. Surprisingly and in contradiction with the hypothesis, the 18F-FLT uptake was not affected by the changes in the MVD.
    Full-text · Article · Sep 2014 · Neuro-Oncology
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    ABSTRACT: AIM: Assessment of amino acid transport using PET tracers such as [18F]-fluor-ethyl-thyrosine (FET) is a valuable supplement to routine contrast enhanced structural MRI in the initial and follow up evaluations of patients with brain tumors. MRI blood volume (BV) imaging using dynamic susceptibility contrast (DSC) has also been shown to give important information about tumor angiogenesis. The aim of the study was to investigate the feasibility of simultaneous imaging of structural MRI, angiogenic activity (BV DSC), and metabolic activity (FET) in a short single session using an integrated PET/MRI scanner. METHODS AND MATERIALS: Twenty-five scans were obtained in 22 referred brain tumor patients. A 20 min static simultaneous PET/MRI (Siemens mMR) acquisition 20 min. p.i. of 200 MBq FET was performed. The MRI protocol included axial FLAIR and post-contrast T1 MPRAGE. For BV imaging the contrast agent (0.1-0.2 ml/kg, Gadovist 1 mmol/ml) was administered using a power injector and BV maps were calculated using dedicated software. Metabolically active tumor volume (FET-vol) was defined in tissue as activity > 1.6 x background activity (B), and metabolic activity, Tmax/B, as maximal tumor activity/B. A low-dose CT scan was obtained for attenuation correction. RESULTS: The PET/MRI scans were well-accepted by patients. Fourteen had high grade glioma (glioblastoma n = 9, oligodendroglioma III n = 4, astrocytoma III n = 1), 7 patients had low grade glioma (ganglioglioma =1, brain stem glioma n = 1, astrocytoma II n = 1, pontine glioma, oligodendroglioma n = 2, unspecified n = 1) and one patients has brain metastasis (malignant melanoma). Five patients had been exposed to anti-angiogenetic chemotherapy (Bevacizumab + irinotecan). Median tumor volume was 1.6 ml (range 0-138 ml). Areas with visually increased BV were observed in 15 of 18 scans with metabolically active tumor tissue. Scans with increased BV had significantly larger median FET-vol (4.1 ml vs 0 ml, p < 0.0005) and median Tmax/B (2.5 vs 1.4, p < 0.005) compared to those with without increased BV. Excluding scans without metabolically active tumor tissue, neither FET-vol nor Tmax/B was different. There was a high variability in the regional signals observed using FLAIR, FET PET, BV, and post-contrast T1, and poor spatial congruence between FET and BV. The fraction of scans with and without increased BV was not related to tumor grade or exposure to Bevacizumab. CONCLUSION: In the clinical management of brain tumors a simultaneous and comprehensive evaluation of structure, metabolism and blood volume is feasible in a short single session FET PET/MRI DSC scan yielding complementary high quality information. This modality may provide valuable insight into tumor biology and increase the overall diagnostic quality, decrease clinical decision time, and increase acceptance of PET imaging with patients and treating clinicians in clinical management and in trials.
    Preview · Article · Sep 2014 · Neuro-Oncology
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    ABSTRACT: BACKGROUND: Recent research shows that the angiogenic mediator Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) is expressed in Glioblastoma Multiforme (GBM) cells and that inhibition of VEGFR2 results in reduced growth of GBM cells. Although autocrine VEGFA-VEGFR2 signaling has been identified in these GBM cells, VEGFA inhibition has very limited effect on growth in the cells, indicating that activation of VEGFR2 in GBM cells not solely is dependent on VEGFA. METHODS: Material consisted of 5 GBM cell cultures established under stem cell conditions and tumors from 18 GBM patients. Angiogenesis-related genes were deregulated using SU1498, recombinant VEGFA-165 and VEGFC protein and VEGFC specific siRNA and a corresponding control. Cell viability was measured using MTT assay, mRNA expression by Q-PCR, protein expression by western blotting and tumor growth by bioluminescence imaging. RESULTS: Examination of a panel of GBM cell cultures identified one culture positive for VEGFR2, while the receptor was undetectable in the remaining cultures. As shown by others, we found that inhibition of receptor phosphorylation by SU1498 resulted in significantly reduced proliferation of the VEGFR2-positive cells. Although VEGFR2 phoshorylation could be stimulated by recombinant VEGFA, inhibition of the VEGFA expressed by the cells using Bevacizumab only had minimal effect on proliferation. Examination of the expression of a range of genes revealed that the VEGFR2 positive cells also were positive for the VEGF variant VEGFC. Addition of recombinant VEGFC protein to the VEGFR2 positive cells resulted in VEGFR2 phosphorylation, while inhibition of VEGFC using specific siRNA constructs resulted in significantly reduced in vitro growth of VEGFR2 positive cells. Moreover, when transplanted as orthotopic brain tumors significantly reduced tumor growth was seen for VEGFC siRNA transfected cells as compared to control cells. In parallel, the median survival was increased from 34 days in mice injected with control cells to 55 days in mice injected with VEGFC siRNA transfected cells. Further, to establish the relevance of VEGFC in GBM patient tumors in general, we measured the VEGFC mRNA level in 18 GBM tumors. Although the level was varying, all examined tumors were positive for VEGFC expression. CONCLUSION: GBM cells can in addition to VEGFA also be dependent on VEGFC for VEGFR2 activation, cell viability and tumor growth.
    Full-text · Article · Sep 2014 · Neuro-Oncology
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    ABSTRACT: It is suggested that Glioblastoma Multiforme (GBM) tumors contain a subpopulation of cells with stem cell features, termed brain cancer stem-like cells (bCSC), which are thought to be involved in tumorigenesis, treatment resistance and recurrence. The epidermal growth factor receptor (EGFR) and the constitutively active deletion variant, termed EGFRvIII, are frequently expressed in GBM and EGFRvIII is correlated to chemo- and radiation resistance and poor patient prognosis. Studies suggest that EGFRvIII is linked to the bCSC subpopulation and that its expression can be regulated by epigenetic treatment. The bCSC are capable of differentiating into more mature cells, and it has been proposed differentiation therapy of bCSC could reduce the self-renewing capacity and decrease the production of clones otherwise able to populate the tumor. Here we wanted to elucidate how the EGFRvIII expression is regulated by epigenetic events during induced differentiation, and which role it plays in the tumorigenic potential. A GBM neurosphere cell culture containing bCSC and expressing endogenous EGFR and EGFRvIII under serum-free conditions was used. When inducing differentiation of the GBM neurospheres by treatment with serum this led to a downregulation of EGFR and EGFRvIII expression. However, upon transfer of the neurospheres back to NB serum-free media the EGFRvIII expression was re-gained. When treating the cells over time with a HDAC inhibitor (TSA) the expression of EGFR, EGFRvIII and the stem cell marker Nestin was decreased. Furthermore, clonal growth in vitro was reduced in a dose-dependent manner by treatment with TSA as shown by a reduction of neurosphere colonies formed in soft agar. Treatment of the neurospheres with the DNA methyl-transferase inhibitor (AZA) reduced their expression of Nestin, whereas the expression of both EGFR and EGFRvIII seemed to be unaffected. When combining serum and TSA treatment, no further downregulation of EGFR/EGFRvIII could be observed. However, GFAP, CNPase and βIII-tubulin were all downregulated as compared to treatment with serum alone, suggesting that TSA impairs serum-induced differentiation of the neurospheres. In addition, treatment with a combination of AZA and serum, for 24 hours, did not affect the expression of EGFR/EGFRvIII but led to increased expression of bIII tubulin, GFAP and CNPase, suggesting induction of neurosphere differentiation. In conclusion these results indicate that treatment with drugs that induce differentiation or modify epigenetic gene expression leads to a decrease in the bCSC subpopulation, possibly via downregulation of signaling pathways, including EGFR/EGFRvIII, involved in bCSC maintenance.
    Preview · Article · Sep 2014 · Neuro-Oncology
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    ABSTRACT: Bevacizumab (BEV), a humanized monoclonal antibody against vascular endothelial growth factor A, has demonstrated activity in patients with recurrent glioblastoma multiforme (GBM). Few previous small sample-size studies have correlated various factors to treatment response, although no predictive parameters have yet been determined. More studies and new approaches to identify the patients that clinically benefit from BEV are therefore in great demand. The primary end-point was to identify the predictive factors of BEV response in patients with recurrent GBM, this single center study retrospectively analyze 196 consecutive, non-selected recurrent primary and secondary GBM patients with ECOG performance status 0-2 who were treated with BEV combination therapy from May 2005 to December 2013. The secondary end-point point was to identify prognostic factors for overall survival (OS) and progression-free survival (PFS). Factors that were analyzed as potential markers of predictive significance included: Age, corticosteroid at start of therapy, increase in corticosteroid dose during the 2 first series, PS at start of therapy, PS after 2 series, PS at best response, gender, extent of resection, tumor location, tumor size, secondary GBM, prior line of chemotherapy, p53, EGFR and MGMT expression. Univariate and multivariate analysis of response data were performed using logistic regression analysis modeling the probability of MacDonald response at 2 months as well as the best response. Estimates of survival probabilities for OS and PFS were performed by Kaplan-Meier method. Univariate and multivariate analyses of OS and PFS for the chosen explanatory variables were performed using Cox regression model. P values <.05 were considered significant. Calculations have been performed using SPSS and SAS software. Results from analysis will be presented.
    Full-text · Article · Sep 2014 · Neuro-Oncology
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    ABSTRACT: ObjectivesBrain tumor imaging is challenging. Although 18F-FET PET is widely used in the clinic, the value of 18F-FET MicroPET to evaluate brain tumors in xenograft has not been assessed to date. The aim of this study therefore was to evaluate the performance of in vivo 18F-FET MicroPET in detecting a treatment response in xenografts. In addition, the correlations between the 18F-FET tumor accumulation and the gene expression of Ki67 and the amino acid transporters LAT1 and LAT2 were investigated. Furthermore, Ki67, LAT1 and LAT2 gene expression in xenograft and archival patient tumors was compared.MethodsHuman GBM cells were injected orthotopically in nude mice and 18F-FET uptake was followed by weekly MicroPET/CT. When tumor take was observed, mice were treated with CPT-11 or saline weekly. After two weeks of treatment the brain tumors were isolated and quantitative polymerase chain reaction were performed on the xenograft tumors and in parallel on archival patient tumor specimens.ResultsThe relative tumor-to-brain (T/B) ratio of SUVmax was significantly lower after one week (123±6%, n = 7 vs. 147±6%, n = 7; p = 0.018) and after two weeks (142±8%, n = 5 vs. 204±27%, n = 4; p = 0.047) in the CPT-11 group compared with the control group. Strong negative correlations between SUVmax T/B ratio and LAT1 (r = −0.62, p = 0.04) and LAT2 (r = −0.67, p = 0.02) were observed. In addition, a strong positive correlation between LAT1 and Ki67 was detected in xenografts. Furthermore, a 1.6 fold higher expression of LAT1 and a 23 fold higher expression of LAT2 were observed in patient specimens compared to xenografts.Conclusions18F-FET MicroPET can be used to detect a treatment response to CPT-11 in GBM xenografts. The strong negative correlation between SUVmax T/B ratio and LAT1/LAT2 indicates an export transport function. We suggest that 18F-FET PET may be used for detection of early treatment response in patients.
    Full-text · Article · Jun 2014 · PLoS ONE
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    ABSTRACT: INTRODUCTION: Brain cancer is uncommon but devastating in young patients. The deleterious cognitive effects of radiation are well documented. Proton radiotherapy promises reduced late effects through better tissue sparing. This has been modeled for selected cases, but not in wider, less biased, populations. Without data from trials comparing radiotherapy techniques, formulae have been proposed correlating radiation dosimetry to cognitive outcomes. METHODS AND MATERIALS: In a province-wide study, all adolescent-young-adult patients treated with photon radiotherapy in Quebec during a 6-month period of 2010 were identified. Of this 114 patient cohort, 19 were treated as children for CNS tumors. After excluding radiosurgery patients, it was possible to replan 10 IMRT cases for intensity modulated proton therapy (IMPT). These patients, aged 2–17, were treated for varied benign and malignant tumors (medulloblastoma, glial and germ cell tumors) to 50.4–59.4 Gy. IMRT and IMPT dose-volume data were applied in 4 published models. Statistical significance was tested using paired t-tests. RESULTS: Compared to photons, IMPT planning predicted modest and variable improvements in the intermediate dose-volumes associated with cognition: mean reduction in whole brain V35-65 of 2% (range -8 to 10, p = 0.02), mean reduction in supratentorial brain V35-65 of 2% (range -1 to 6, p = 0.04), mean reduction in temporal lobe V40 of 4% (range -40 to 38, p = 0.4). All models predicted that IMPT would lessen the impact of treatment on IQ by an average of 2-4 points at 5 years. Unrealistically, post-treatment IQ improvement was often predicted especially for older children. CONCLUSION: Our results suggest that increasing use of proton therapy will likely improve cognitive outcomes in young brain tumor patients. Current models may not reliably predict the magnitude of this improvement underlining the need to collect more data, particularly in patients treated as adolescents and with a wider range of diagnoses and radiation techniques.
    Full-text · Conference Paper · Nov 2013

Publication Stats

1k Citations
404.15 Total Impact Points

Institutions

  • 1999-2014
    • Copenhagen University Hospital
      København, Capital Region, Denmark
  • 1991-2012
    • Rigshospitalet
      • Department of Oncology
      København, Capital Region, Denmark
  • 1999-2010
    • National University (California)
      San Diego, California, United States
  • 2005
    • Louisiana State University Health Sciences Center New Orleans
      • Department of Pediatrics
      New Orleans, Louisiana, United States