@article {93, title = {The posterior cerebellum, a new organ at risk?}, journal = {Clinical and Translational Radiation Oncology}, volume = {8}, year = {2018}, month = {Jan-01-2018}, pages = {22 - 26}, abstract = {

Eekers et al. have recently proposed a neuro-oncology atlas [doi:10.17195/candat.2017.08.1, Ed.], which was co-authored by most centers associated in the European Proton Therapy Network (EPTN). With the introduction of new treatment techniques, such as integrated magnetic resonance imaging and linear accelerators (MR-linac) or particle therapy, the prediction of clinical efficacy of these more costly treatment modalities becomes more relevant. One of the side-effects of brain irradiation, being cognitive decline, is one of the toxicities most difficult to measure and predict. In order to validly compare different treatment modalities, 1) a uniform nomenclature of the organs at risk (OARs), 2) uniform atlas-based delineation [e.g., Eekers et al.], 3) long-term follow-up data with standardized cognitive tests, 4) a large patient population, and 5) (thus derived) validated normal tissue complication probability (NTCP) models are mandatory.

Apart from the Gondi model, in which the role of the dose to 40\% of both hippocampi (HC) proves to be significantly related to cognition in 18 patients, no similar models are available. So there is a strong need for more NTCP models, on HC, brain tissue and possible other relevant brain structures.

In this review we summarize the available evidence on the role of the posterior cerebellum as a possible new organ at risk for cognition, which is deemed relevant for irradiation of brain and head and neck tumors.

}, keywords = {Cognition, Delineation atlas, Neuro-oncology, Organ at risk, Posterior cerebellum, Radiotherapy}, issn = {24056308}, doi = {10.1016/j.ctro.2017.11.010}, url = {http://linkinghub.elsevier.com/retrieve/pii/S2405630817300769}, author = {Eekers, Dani{\"e}lle B.P. and Lieke in {\textquoteright}t Ven and Deprez, Sabine and Jacobi, Linda and Erik Roelofs and Ann Hoeben and Lambin, Philippe and Dirk De Ruysscher and Troost, Esther G.C.} } @article {55, title = {PET-based dose painting in non-small cell lung cancer: Comparing uniform dose escalation with boosting hypoxic and metabolically active sub-volumes.}, journal = {Radiother Oncol}, volume = {116}, year = {2015}, month = {2015 Aug}, pages = {281-6}, abstract = {

BACKGROUND AND PURPOSE: We compared two imaging biomarkers for dose-escalation in patients with advanced non-small cell lung cancer (NSCLC). Treatment plans boosting metabolically active sub-volumes defined by FDG-PET or hypoxic sub-volumes defined by HX4-PET were compared with boosting the entire tumour.

MATERIALS AND METHODS: Ten NSCLC patients underwent FDG- and HX4-PET/CT scans prior to radiotherapy. Three isotoxic dose-escalation plans were compared per patient: plan A, boosting the primary tumour (PTVprim); plan B, boosting sub-volume with FDG >50\% SUVmax (PTVFDG); plan C, boosting hypoxic volume with HX4 tumour-to-background >1.4 (PTVHX4).

RESULTS: Average boost volumes were 507 {\textpm} 466 cm(3) for PTVprim, 173 {\textpm} 127 cm(3) for PTVFDG and 114 {\textpm} 73 cm(3) for PTVHX4. The smaller PTVHX4 overlapped on average 87 {\textpm} 16\% with PTVFDG. Prescribed dose was escalated to 87 {\textpm} 10 Gy for PTVprim, 107 {\textpm} 20 Gy for PTVFDG, and 117 {\textpm} 15 Gy for PTVHX4, with comparable doses to the relevant organs-at-risk (OAR). Treatment plans are available online (https://www.cancerdata.org/10.1016/j.radonc.2015.07.013).

CONCLUSIONS: Dose escalation based on metabolic sub-volumes, hypoxic sub-volumes and the entire tumour is feasible. Highest dose was achieved for hypoxia plans, without increasing dose to OAR. For most patients, boosting the metabolic sub-volume also resulted in boosting the hypoxic volume, although to a lower dose, but not vice versa.

}, keywords = {Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung, Cell Hypoxia, Female, Humans, Lung Neoplasms, Male, Middle Aged, Positron-Emission Tomography, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted}, issn = {1879-0887}, doi = {10.1016/j.radonc.2015.07.013}, author = {Even, Aniek J G and van der Stoep, Judith and Zegers, Catharina M L and Reymen, Bart and Troost, Esther G C and Lambin, Philippe and van Elmpt, Wouter} } @article {47, title = {Prognostic value of metabolic metrics extracted from baseline positron emission tomography images in non-small cell lung cancer.}, journal = {Acta Oncol}, volume = {52}, year = {2013}, month = {2013 Oct}, pages = {1398-404}, abstract = {

BACKGROUND: Maximum, mean and peak SUV of primary tumor at baseline FDG-PET scans, have often been found predictive for overall survival in non-small cell lung cancer (NSCLC) patients. In this study we further investigated the prognostic power of advanced metabolic metrics derived from intensity volume histograms (IVH) extracted from PET imaging.

METHODS: A cohort of 220 NSCLC patients (mean age, 66.6 years; 149 men, 71 women), stages I-IIIB, treated with radiotherapy with curative intent were included (NCT00522639). Each patient underwent standardized pre-treatment CT-PET imaging. Primary GTV was delineated by an experienced radiation oncologist on CT-PET images. Common PET descriptors such as maximum, mean and peak SUV, and metabolic tumor volume (MTV) were quantified. Advanced descriptors of metabolic activity were quantified by IVH. These comprised five groups of features: absolute and relative volume above relative intensity threshold (AVRI and RVRI), absolute and relative volume above absolute intensity threshold (AVAI and RVAI), and absolute intensity above relative volume threshold (AIRV). MTV was derived from the IVH curves for volumes with SUV above 2.5, 3 and 4, and of 40\% and 50\% maximum SUV. Univariable analysis using Cox Proportional Hazard Regression was performed for overall survival assessment.

RESULTS: Relative volume above higher SUV (80\%) was an independent predictor of OS (p = 0.05). None of the possible surrogates for MTV based on volumes above SUV of 3, 40\% and 50\% of maximum SUV showed significant associations with OS [p (AVAI3) = 0.10, p (AVAI4) = 0.22, p (AVRI40\%) = 0.15, p (AVRI50\%) = 0.17]. Maximum and peak SUV (r = 0.99) revealed no prognostic value for OS [p (maximum SUV) = 0.20, p (peak SUV) = 0.22].

CONCLUSIONS: New methods using more advanced imaging features extracted from PET were analyzed. Best prognostic value for OS of NSCLC patients was found for relative portions of the tumor above higher uptakes (80\% SUV).

}, keywords = {Aged, Carcinoma, Non-Small-Cell Lung, Female, Fluorodeoxyglucose F18, Humans, Lung Neoplasms, Male, Neoplasm Staging, Positron-Emission Tomography, Prognosis, Radiopharmaceuticals, Radiotherapy Planning, Computer-Assisted, Radiotherapy, Image-Guided, Tumor Burden}, issn = {1651-226X}, doi = {10.3109/0284186X.2013.812795}, author = {Carvalho, Sara and Leijenaar, Ralph T H and Velazquez, Emmanuel Rios and Oberije, Cary and Parmar, Chintan and van Elmpt, Wouter and Reymen, Bart and Troost, Esther G C and Oellers, Michel and Dekker, Andre and Gillies, Robert and Aerts, Hugo J W L and Lambin, Philippe} } @article {35, title = {The prognostic value of temporal in vitro and in vivo derived hypoxia gene-expression signatures in breast cancer}, journal = {Radiotherapy and Oncology}, volume = {102}, year = {2012}, month = {Jan-03-2012}, pages = {436 - 443}, issn = {01678140}, doi = {10.1016/j.radonc.2012.02.002}, url = {http://linkinghub.elsevier.com/retrieve/pii/S016781401200059X}, author = {Starmans, Maud H.W. and Chu, Kenneth C. and Haider, Syed and Nguyen, Francis and Seigneuric, Renaud and Magagnin, Michael G. and Koritzinsky, Marianne and Kasprzyk, Arek and Boutros, Paul C. and Wouters, Bradly G. and P. Lambin} } @article {36, title = {Preclinical evaluation and validation of [18F]HX4, a promising hypoxia marker for PET imaging}, journal = {Proceedings of the National Academy of Sciences}, volume = {108}, year = {2011}, month = {Jun-08-2013}, pages = {14620 - 14625}, issn = {0027-8424}, doi = {10.1073/pnas.1102526108}, url = {http://www.pnas.org/cgi/doi/10.1073/pnas.1102526108}, author = {L. J. Dubois and Lieuwes, N. G. and Marco H. M. Janssen and Peeters, W. J. M. and Windhorst, A. D. and Walsh, J. C. and H. C. Kolb and M. C. Oellers and Johan Bussink and van Dongen, G. A. M. S. and van der Kogel, A. and P. Lambin} } @article {37, title = {PET imaging of hypoxia using [18F]HX4: a phase I trial}, journal = {European Journal of Nuclear Medicine and Molecular Imaging}, volume = {37}, year = {2010}, month = {Jan-08-2010}, pages = {1663 - 1668}, abstract = {

Download the images using\ these instructions\ and this DOI :\ 10.1007/s00259-010-1437-x

Background and purpose
Non-invasive PET imaging of tumour hypoxia could help in the selection of those patients who could benefit from chemotherapy or radiation with specific antihypoxic treatments such as bioreductive drugs or hypoxic radiosensitizers. In this phase I trial, we aimed to determine the toxicity of [18F]HX4, a member of the 2-nitroimidazole family, at different dose levels. The secondary aim was to analyse image quality related to the HX4 dose and the timing of imaging.

Methods
Patients with a histologically proven solid cancer without curative treatment options were eligible for this study. A study design with two dose steps was used in which a single dose of a maximum of 222MBq (step 1) or 444 MBq (step 2) [18F]HX4 was injected. Toxicity was scored on day 0 and on days 3 and 7 after injection, according to the CTCAE 3.0 scoring system. PET/CT images of the largest tumour site were acquired 30, 60 and 120 min after injection.

Results
Six patients with stage IV carcinoma were included, four with non-small-cell lung carcinoma, one with thymus carcinoma, and one with colon carcinoma. No toxicity was observed in any of the patients at either dose level. The median tumour to muscle ratio 120 min after injection was 1.40 (range 0.63{\textendash}1.98).

Conclusion\ 
The findings of this study showed that [18F] HX4 PET imaging for the detection of hypoxia is not associated with any toxicity. Imaging was successful; however, future trials are needed to determine the optimal image parameters.

}, keywords = {2-Nitroimidazoles, HX4, Hypoxia, PET}, issn = {1619-7070}, doi = {10.1007/s00259-010-1437-x}, url = {http://link.springer.com/10.1007/s00259-010-1437-x}, author = {Loon, Judith and Marco H. M. Janssen and M. C. Oellers and Hugo J. W. L. Aerts and L. J. Dubois and Hochstenbag, Monique and Anne-Marie C. Dingemans and Lalisang, Roy and Brans, Boudewijn and Windhorst, Bert and Dongen, Guus A. and H. C. Kolb and Zhang, James and Dirk De Ruysscher and P. Lambin} } Error | CancerData.org

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