139 results on '"tumour oxygenation"'
Search Results
2. Biologically-optimised IMRT based on molecular imaging of tumour hypoxia–the impact of the tracer used
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Toma-Dasu, I., Dasu, A., and Long, Mian, editor
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- 2013
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3. Quantifying Tumour Hypoxia By Pet Imaging - A Theoretical Analysis
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Toma-Daşu, Iuliana, Daşuu, Alexandru, Brahmeu, Anders, Back, Nathan, editor, Cohen, Irun R., editor, Lajtha, Abel N.S., editor, Lambris, John D., editor, Paoletti, Rodolfo, editor, Liss, Per, editor, Hansell, Peter, editor, Bruley, Duane F., editor, and Harrison, David K., editor
- Published
- 2009
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4. The Relationship Between Vascular Oxygen Distribution And Tissue Oxygenation
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Daşu, Alexandru, Toma-Daşu, Iuliana, Back, Nathan, editor, Cohen, Irun R., editor, Lajtha, Abel N.S., editor, Lambris, John D., editor, Paoletti, Rodolfo, editor, Liss, Per, editor, Hansell, Peter, editor, Bruley, Duane F., editor, and Harrison, David K., editor
- Published
- 2009
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5. The effect of rhEPO on survival in anemic cancer patients
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Littlewood, Tim J. and Nowrousian, Mohammad Resa, editor
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- 2008
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6. Exogenous and Endogenous Markers of Tumour Oxygenation Status : Definitive markers of tumour hypoxia?
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Williams, Kaye J., Parker, Catriona A., Stratford, Ian J., Back, Nathan, editor, Cohen, Irun R., editor, Kritchevsky, David, editor, Lajtha, Abel, editor, Paoletti, Rodolfo, editor, Okunieff, Paul, editor, Williams, Jacqueline, editor, and Chen, Yuhchyau, editor
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- 2005
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7. The Effects of Tumour Blood Flow and Oxygenation Modifiers on Subcutaneous Tumours as Determined by NIRS
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Howe, Franklyn A., Connelly, James P., Robinson, Simon P., Springett, Roger, Griffiths, John R., Back, Nathan, editor, Cohen, Irun R., editor, Kritchevsky, David, editor, Lajtha, Abel, editor, Paoletti, Rodolfo, editor, Okunieff, Paul, editor, Williams, Jacqueline, editor, and Chen, Yuhchyau, editor
- Published
- 2005
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8. Effect of Breathing Carbogen on the Oxygen Tension Of Murine and Human Tumours Measured Using an Eppendorf pO2 Histograph
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Minchinton, Andrew I., Fryer, Karen H., Lim, Peter, Aquino-Parsons, Christina, Eke, Andras, editor, and Delpy, David T., editor
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- 1999
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9. Tumour Oxygenation : The Influence of Normobaric and Hyperbaric Oxygen
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van der Kleij, A. J., Kooijman, R., Kipp, J. B. A., Obertop, H., Ince, C., editor, Kesecioglu, J., editor, Telci, L., editor, and Akpir, K., editor
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- 1996
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10. Measurement of PO2 in a Murine Tumour and Its Correlation with Hypoxic Fraction
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Horsman, Michael R., Khalil, Azza A., Nordsmark, Marianne, Grau, Cai, Overgaard, Jens, Vaupel, Peter, editor, Zander, Rolf, editor, and Bruley, Duane F., editor
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- 1994
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11. Tumour Radiosensitization by Nicotinamide: Is It the Result of an Improvement in Tumour Oxygenation?
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Horsman, Michael R., Nordsmark, Marianne, Khalil, Azza, Chaplin, David J., Overgaard, Jens, Vaupel, Peter, editor, Zander, Rolf, editor, and Bruley, Duane F., editor
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- 1994
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12. The Combination of Nicotinamide and Carbogen Breathing to Improve Tumour Oxygenation Prior to Radiation Treatment
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Horsman, Michael R., Siemann, Dietmar W., Nordsmark, Marianne, Khalil, Azza A., Overgaard, Jens, Chaplin, David J., Hogan, Michael C., editor, Mathieu-Costello, Odile, editor, Poole, David C., editor, and Wagner, Peter D., editor
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- 1994
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13. Pre-radiotherapy Haemoglobin Level is A Prognosticator in Locally Advanced Head and Neck Cancers Treated with Concurrent Chemoradiation
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Rajesh Kar Narayanaswamy, Mahadev Potharaju, A N Vaidhyswaran, and Karthikeyan Perumal
- Subjects
haemoglobin concentration ,hypoxia ,oxygen transport capacity ,tumour oxygenation ,Medicine - Abstract
Introduction: Radiation plays a major role in treatment of locoregional control of Head and Neck Squamous cell carcinoma (HNSCC). Anaemia is considered a contributor to intra-tumour hypoxia and tumour resistance to ionizing radiation and most evidences are from developed world, we prospectively investigated the exact role of anaemia in treatment outcome of Stage III/IVA HNSCC in our patient population. Aim of the Study: Primary end point: To analyse the PreRadiotherapy haemoglobin level and early response of treatment in stage III/IVA HNSCC and to determine the relationship of Pre-Radiotherapy haemoglobin level with other prognostic factors. Materials and Methods: This non-interventional single blinded randomized study enrolled patients attending the OPD consecutively, who met our eligibility criteria. Inclusion Criteria: HNSCC patients of Stage III/IVA aged ≥18 years and ≤ 70 years with ECOG status of 1or 2 and willing for concurrent chemoradiation and at least 6 weeks of follow up. Exclusion Criteria: 1) Previous history of treatment for malignancy or radiation in head and neck site. 2) Patients with other fatal and non-fatal pre-morbid or co-morbid conditions that can affect the outcome or the overall survival. Patients with Pre-radiotherapy haemoglobin status < 10 g/dl were given haematinic support and/or blood transfusion. All patients received concurrent chemotherapy (weekly cisplatin) and radiation in conventionally fractionated dose of 66Gy. Early treatment responses were evaluated with Revised RECIST version 1.1 and Data analysis using SPSS version 17.0. Results: Ninety one patients enrolled had mean age of 55.63 (range: 32-69), a median of 56 and mode of 60. Seventy one were males (78%) and 20 females (22%) with a performance status of ECOG 1 in 43 (47%) patients and ECOG 2 in 48 (53%); Pre-RT Hb level of 5 days (p = 5 days and nondevelopment of grade III mucositis was found to be significantly associated with good loco-regional control. Haemoglobin level ≥10.7 g/dl was associated with better treatment outcome, higher performance status, fewer treatment interruptions and lesser degree of mucositis. Transfusion did not affect the outcome. Definitive conclusions and recommendations need further expansion of our study for better statistical power.
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- 2015
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14. The Control of Tumour Oxygenation in Mice: The Importance of Tumour Site
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Hirst, David G., Hill, Sally A., Adams, G. E., editor, Breccia, A., editor, Fielden, E. M., editor, and Wardman, P., editor
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- 1990
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15. Perfluorochemicals and Photodynamic Therapy in Mice
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Berenbaum, M. C., Akande, S. L., Armstrong, F. H., Bentley, P. K., Bonnett, R., White, R. D., Lowe, K. C., Piiper, Johannes, editor, Goldstick, Thomas K., editor, and Meyer, Michael, editor
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- 1990
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16. Tumour Radiosensitization by Clofibrate and its Analogs: Possible Mechanisms
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Hirst, David G., Piiper, Johannes, editor, Goldstick, Thomas K., editor, and Meyer, Michael, editor
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- 1990
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17. Hypoxia Induced by Vascular Damage at High Doses Could Compromise the Outcome of Radiotherapy
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Emely Lindblom, Iuliana Toma-Dasu, and Alexandru Dasu
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Cancer Research ,medicine.medical_specialty ,Cell Survival ,medicine.medical_treatment ,Radiosurgery ,Models, Biological ,Radiation Tolerance ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Vascular collapse ,medicine ,High doses ,Humans ,Computer Simulation ,Hypoxia ,business.industry ,General Medicine ,Hypoxia (medical) ,Tumour oxygenation ,Oxygen ,Radiation therapy ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Blood Vessels ,Dose Fractionation, Radiation ,Radiology ,medicine.symptom ,business ,Stereotactic body radiotherapy - Abstract
This study investigated the impact of temporary vascular collapse on tumour control probability (TCP) in stereotactic body radiotherapy (SBRT), taking into account different radiosensitivities of chronically and acutely hypoxic cells.Three-dimensional tumours with heterogeneous oxygenation were simulated assuming different fractions of collapsed vessels at every treatment fraction. The modelled tumours contained a chronically hypoxic subvolume of 30-60% of the tumour diameter, and a hypoxic fraction ≤5 mm Hg of 30-50%. The rest of the tumours were well-oxygenated at the start of the simulated treatment.For all simulated cases, the largest reduction in TCP from 97% to 2% was found in a tumour with a small chronically hypoxic core treated with 60 Gy in eight fractions and assuming a treatment-induced vascular collapse of 35% in the well-oxygenated region.The timing of SBRT fractions should be considered together with the tumour oxygenation to avoid loss of TCP in SBRT.
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- 2019
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18. Measurement of the acute metabolic response to hypoxia in rat tumours in vivo using magnetic resonance spectroscopy and hyperpolarised pyruvate.
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Bluff, Joanne E., Reynolds, Steven, Metcalf, Stephen, Alizadeh, Tooba, Kazan, Samira M., Bucur, Adriana, Wholey, Emily G., Bibby, Becky A.S., Williams, Leigh, Paley, Martyn N., and Tozer, Gillian M.
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TUMOR diagnosis , *HYPOXEMIA , *NUCLEAR magnetic resonance spectroscopy , *PYRUVATES , *METABOLISM , *LABORATORY rats - Abstract
Purpose To estimate the rate constant for pyruvate to lactate conversion in tumours in response to a hypoxic challenge, using hyperpolarised 13 C 1 -pyruvate and magnetic resonance spectroscopy. Methods and materials Hypoxic inspired gas was used to manipulate rat P22 fibrosarcoma oxygen tension (pO 2 ), confirmed by luminescence decay of oxygen-sensitive probes. Hyperpolarised 13 C 1 -pyruvate was injected into the femoral vein of anaesthetised rats and slice-localised 13 C magnetic resonance (MR) spectra acquired. Spectral integral versus time curves for pyruvate and lactate were fitted to a precursor-product model to estimate the rate constant for tumour conversion of pyruvate to lactate ( k pl ). Mean arterial blood pressure (MABP) and oxygen tension (ArtpO 2 ) were monitored. Pyruvate and lactate concentrations were measured in freeze-clamped tumours. Results MABP, ArtpO 2 and tumour pO 2 decreased significantly during hypoxia. k pl increased significantly ( p < 0.01) from 0.029 ± 0.002 s −1 to 0.049 ± 0.006 s −1 (mean ± SEM) when animals breathing air were switched to hypoxic conditions, whereas pyruvate and lactate concentrations were minimally affected by hypoxia. Both ArtpO 2 and MABP influenced the estimate of k pl , with a strong negative correlation between k pl and the product of ArtpO 2 and MABP under hypoxia. Conclusion The rate constant for pyruvate to lactate conversion, k pl , responds significantly to a rapid reduction in tumour oxygenation. [ABSTRACT FROM AUTHOR]
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- 2015
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19. Pre-radiotherapy Haemoglobin Level is A Prognosticator in Locally Advanced Head and Neck Cancers Treated with Concurrent Chemoradiation.
- Author
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NARAYANASWAMY, RAJESH KAR, POTHARAJU, MAHADEV, VAIDHYSWARAN, A. N., and PERUMAL, KARTHIKEYAN
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HEAD & neck cancer , *HEMOGLOBINS , *RADIOTHERAPY , *ELECTROTHERAPEUTICS , *CLINICAL medicine , *MEDICAL care - Abstract
Introduction: Radiation plays a major role in treatment of locoregional control of Head and Neck Squamous cell carcinoma (HNSCC). Anaemia is considered a contributor to intra-tumour hypoxia and tumour resistance to ionizing radiation and most evidences are from developed world, we prospectively investigated the exact role of anaemia in treatment outcome of Stage III/IVA HNSCC in our patient population. Aim of the Study: Primary end point: To analyse the Pre- Radiotherapy haemoglobin level and early response of treatment in stage III/IVA HNSCC and to determine the relationship of Pre-Radiotherapy haemoglobin level with other prognostic factors. Materials and Methods: This non-interventional single blinded randomized study enrolled patients attending the OPD consecutively, who met our eligibility criteria. Inclusion Criteria: HNSCC patients of Stage III/IVA aged ≥18 years and ≤ 70 years with ECOG status of 1or 2 and willing for concurrent chemoradiation and at least 6 weeks of follow up. Exclusion Criteria: 1) Previous history of treatment for malignancy or radiation in head and neck site. 2) Patients with other fatal and non-fatal pre-morbid or co-morbid conditions that can affect the outcome or the overall survival. Patients with Pre-radiotherapy haemoglobin status < 10 g/dl were given haematinic support and/or blood transfusion. All patients received concurrent chemotherapy (weekly cisplatin) and radiation in conventionally fractionated dose of 66Gy. Early treatment responses were evaluated with Revised RECIST version 1.1 and Data analysis using SPSS version 17.0. Results: Ninety one patients enrolled had mean age of 55.63 (range: 32-69), a median of 56 and mode of 60. Seventy one were males (78%) and 20 females (22%) with a performance status of ECOG 1 in 43 (47%) patients and ECOG 2 in 48 (53%); Pre-RT Hb level of <10.7 g/dl in 38 (42%) patients and ≥10.7 in 53 (58%) patients; Pre-RT Hb level was <12 g/dl in 67 (74%) patients and ≥12 in 24 (26%) patients. Tumour sites were - Nasopharynx 7 (8 %), Oral Cavity 18 (20 %), Oropharynx 32 (35 %), Hypopharynx 23 (25 %) and Larynx 11 (12 %). Twenty five (27%) had Grade 2 mucositis and 66 (73%) had Grade 3 mucositis. Fifty eight (64%) patients completed treatment with NO breaks and 33 (36%) with treatment breaks for ≥5 days. Pre-radiotherapy haemoglobin ≥ 10.7 g/dl (p < 0.001), ECOG performance status (p = 0.0002), Treatment interruptions for > 5 days (p = <0.0001), Mucositis reaction (p = <0.0001) showed statistical significance with outcome of response. Conclusion: The study found that performance status, pre-RT haemoglobin level, radiotherapy interruptions > 5 days and nondevelopment of grade III mucositis was found to be significantly associated with good loco-regional control. Haemoglobin level ≥10.7 g/dl was associated with better treatment outcome, higher performance status, fewer treatment interruptions and lesser degree of mucositis. Transfusion did not affect the outcome. Definitive conclusions and recommendations need further expansion of our study for better statistical power. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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- View/download PDF
20. PO-1805 In silico tumour modelling accounting for tumour oxygenation and its dynamics
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Iuliana Toma-Dasu, F. Schiavo, and E. Kjellsson Lindblom
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Oncology ,Chemistry ,In silico ,Dynamics (mechanics) ,Radiology, Nuclear Medicine and imaging ,Hematology ,Computational biology ,Tumour oxygenation - Published
- 2021
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21. Impact of hyperthermic isolated limb perfusion on tumour oxygenation in soft tissue sarcoma.
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Jakob, Jens, von Rege, Inez, Weiss, Christel, and Hohenberger, Peter
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FEVER , *PERFUSION , *OXYGENATION (Chemistry) , *SOFT tissue tumors , *TUMOR necrosis factors - Abstract
Purpose: Hyperthermic isolated limb perfusion (ILP) with recombinant tumour necrosis factor alpha (TNF) and melphalan contributes to limb-saving treatment in patients with locally advanced extremity soft tissue sarcoma (STS). This study was conducted to evaluate the dynamic changes of tumour oxygenation and temperature during ILP and their effects on treatment response. Patients and methods: Tumour oxygenation (pO2) and tumour temperature were measured by intratumourally placed O2-sensitive catheter electrodes in 34 patients who underwent ILP for locally advanced or recurrent STS. Tumour response to ILP was assessed by the fraction of tumour necrosis in the resection specimen. Results: Mean tumour pO2 prior to application of TNF and melphalan was 36 mm Hg (range: 2-116 mm Hg) and dropped significantly to 13 mm Hg (range: 0-67 mm Hg, p = 0.03) during ILP. Mean tumour tissue temperature increased from 34.4°C (range 32.4-36.4) to 38.5°C (range 34.1-40.4, p = 0.0001). The mean fraction of necrosis in the resection specimen was 65% (range 5-99). Only the tumour tissue temperature at the onset of ILP correlated with the extent of tumour necrosis ( p = 0.01). Conclusion: ILP with TNF and melphalan induces severe oxygen deprivation in soft tissue sarcoma. However, changes in tumour oxygenation did not correlate with treatment response. [ABSTRACT FROM AUTHOR]
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- 2012
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22. Pathophysiological and vascular characteristics of tumours and their importance for hyperthermia: Heterogeneity is the key issue.
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Vaupel, Peter W. and Kelleher, Debra K.
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TUMORS , *FEVER , *BLOOD flow , *PATHOLOGICAL physiology , *HEMODYNAMICS - Abstract
Tumour blood flow before and during clinically relevant mild hyperthermia exhibits pronounced heterogeneity. Flow changes upon heating are not predictable and are both spatially and temporally highly variable. Flow increases may result in improved heat dissipation to the extent that therapeutically relevant tissue temperatures may not be achieved. This holds especially true for tumours or tumour regions in which flow rates are substantially higher than in the surrounding normal tissues. Changes in tumour oxygenation tend to reflect alterations in blood flow upon hyperthermia. An initial improvement in the oxygenation status, followed by a return to baseline levels (or even a drop to below baseline at high thermal doses) has been reported for some tumours, whereas a predictable and universal occurrence of sustained increases in O2 tensions upon mild hyperthermia is questionable and still needs to be verified in the clinical setting. Clarification of the pathogenetic mechanisms behind possible sustained increases is mandatory. High-dose hyperthermia leads to a decrease in the extracellular and intracellular pH and a deterioration of the energy status, both of which are known to be parameters capable of acting as direct sensitisers and thus pivotal factors in hyperthermia treatment. The role of the tumour microcirculatory function, hypoxia, acidosis and energy status is complex and is further complicated by a pronounced heterogeneity. These latter aspects require additional critical evaluation in clinically relevant tumour models in order for their impact on the response to heat to be clarified. [ABSTRACT FROM AUTHOR]
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- 2010
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23. Dose prescription and optimisation based on tumour hypoxia.
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Toma-Daşu, Iuliana, Daşu, Alexandru, and Brahme, Anders
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TUMORS , *HYPOXEMIA , *RADIOTHERAPY , *RADIATION , *ASPHYXIA - Abstract
Introduction. Tumour hypoxia is an important factor that confers radioresistance to the affected cells and could thus decrease the tumour response to radiotherapy. The development of advanced imaging methods that quantify both the extent and the spatial distribution of the hypoxic regions has created the premises to devise therapies that target the hypoxic regions in the tumour. Materials and methods. The present study proposes an original method to prescribe objectively dose distributions that focus the radiation dose to the radioresistant tumour regions and could therefore spare adjacent normal tissues. The effectiveness of the method was tested for clinically relevant simulations of tumour hypoxia that take into consideration dynamics and heterogeneity of oxygenation. Results and discussion. The results have shown that highly heterogeneous dose distributions may lead to significant improvements of the outcome only for static oxygenations. In contrast, the proposed method that involves the segmentation of the dose distributions and the optimisation of the dose prescribed to each segment to account for local heterogeneity may lead to significantly improved local control for clinically-relevant patterns of oxygenation. The clinical applicability of the method is warranted by its relatively easy adaptation to functional imaging of tumour hypoxia obtained with markers with known uptake properties. [ABSTRACT FROM AUTHOR]
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- 2009
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24. Nitric oxide delivery to cancer: Why and how?
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Sonveaux, Pierre, Jordan, Bénédicte F., Gallez, Bernard, and Feron, Olivier
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THERAPEUTIC use of nitric oxide , *HYPOXEMIA , *BLOOD flow , *CANCER radiotherapy , *CANCER chemotherapy , *CELL respiration , *HYPERBARIC oxygenation - Abstract
Abstract: Hypoxia and blood flow heterogeneities are characteristics of solid tumours and are major obstacles for therapy. Exploiting the biology of nitric oxide (NO), a small radical with multiple functions, is particularly attractive to circumvent these sources of resistance and to sensitise tumour to cytotoxic treatments such as radiotherapy and chemotherapy. Indeed, while NO mediates angiogenic effects, NO may also promote tumour perfusion, drug delivery and oxygenation. Different strategies to deliver NO to tumours and pertaining to the FECS-EJC award laureate’s work are reviewed, with a focus on their therapeutic potential. The development of techniques to monitor how and to which extent NO delivery influences the phenotype of a given tumour in a given patient is also discussed. [Copyright &y& Elsevier]
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- 2009
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25. Non-linear conversion of HX4 uptake for automatic segmentation of hypoxic volumes and dose prescription
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Ana Ureba, Philippe Lambin, Wouter van Elmpt, Peter Wersäll, Emely Lindblom, Aniek J.G. Even, Alexandru Dasu, Iuliana Toma-Dasu, J. Uhrdin, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and Radiotherapie
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Fluorine Radioisotopes ,Lung Neoplasms ,medicine.medical_treatment ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,RADIATION-THERAPY ,Carcinoma, Non-Small-Cell Lung ,Radioresistance ,medicine ,ESCALATION ,Humans ,Radiology, Nuclear Medicine and imaging ,Radiation treatment planning ,Tumor hypoxia ,business.industry ,Radiotherapy Planning, Computer-Assisted ,Imidazoles ,Hematology ,General Medicine ,Triazoles ,Tumour oxygenation ,Dose prescription ,MODEL ,Radiation therapy ,PET ,Oncology ,Positron-Emission Tomography ,030220 oncology & carcinogenesis ,Anesthesia ,Tumor Hypoxia ,Automatic segmentation ,FMISO ,Radiopharmaceuticals ,business ,Biomedical engineering - Abstract
Background: Tumour hypoxia is associated with increased radioresistance and poor response to radiotherapy. Pre-treatment assessment of tumour oxygenation could therefore give the possibility to tailor the treatment by calculating the required boost dose needed to overcome the increased radioresistance in hypoxic tumours. This study concerned the derivation of a non-linear conversion function between the uptake of the hypoxia-PET tracer F-18-HX4 and oxygen partial pressure (pO(2)).Material and methods: Building on previous experience with FMISO including experimental data on tracer uptake and pO(2), tracer-specific model parameters were derived for converting the normalised HX4-uptake at the optimal imaging time point to pO(2). The conversion function was implemented in a Python-based computational platform utilising the scripting and the registration modules of the treatment planning system RayStation. Subsequently, the conversion function was applied to determine the pO(2) in eight non-small-cell lung cancer (NSCLC) patients imaged with HX4-PET before the start of radiotherapy. Automatic segmentation of hypoxic target volumes (HTVs) was then performed using thresholds around 10mmHg. The HTVs were compared to sub-volumes segmented based on a tumour-to-blood ratio (TBR) of 1.4 using the aortic arch as the reference oxygenated region. The boost dose required to achieve 95% local control was then calculated based on the calibrated levels of hypoxia, assuming inter-fraction reoxygenation due to changes in acute hypoxia but no overall improvement of the oxygenation status.Results: Using the developed conversion tool, HTVs could be obtained using pO(2) a threshold of 10mmHg which were in agreement with the TBR segmentation. The dose levels required to the HTVs to achieve local control were feasible, being around 70-80Gy in 24 fractions.Conclusions: Non-linear conversion of tracer uptake to pO(2) in NSCLC imaged with HX4-PET allows a quantitative determination of the dose-boost needed to achieve a high probability of local control.
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- 2017
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26. Tumour hypoxia: lessons learnt from preclinical imaging
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Silvia Valtorta, Isabella Raccagni, Rosa Maria Moresco, Sara Belloli, Raccagni, I, Valtorta, S, Moresco, R, and Belloli, S
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Oncology ,Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,PET imaging ,Hypoxia-specific radiopharmaceutical ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Preclinical research ,Hypoxia-specific radiopharmaceuticals ,0302 clinical medicine ,Internal medicine ,medicine ,Radiology, Nuclear Medicine and imaging ,Treatment outcome ,Treatment resistance ,Hypoxia ,business.industry ,Pet imaging ,Hypoxia (medical) ,Tumour oxygenation ,Preclinical ,Radiation therapy ,030220 oncology & carcinogenesis ,Tracer uptake ,medicine.symptom ,business ,Preclinical imaging - Abstract
Purpose: In tumour, the imbalance between oxygen supply and demand leads to hypoxia, which represents a negative prognostic factor associated with aggressive tumour phenotype and therapy resistance. This review provides an overview of the use of positron emitter-labelled radiopharmaceutical used to image hypoxia in preclinical models of cancer. Methods: A critical and comprehensive PubMed search was performed identifying articles related to PET imaging for hypoxia assessment in preclinical setting from January 2007 up to January 2017. Results: We have considered and described a total of 54 original articles, exploring tumour-associated hypoxia in preclinical models. Results underlined the potential application together with the advantages and pitfalls of the use of PET in preclinical research. Multi-target imaging allowed to better define the relationship between hypoxia and other biological hallmarks of tumour; imaging of hypoxia was proved as a useful tool for lesions stratification and response prediction to radiotherapy; however, cutoff indexes were identified in few studies. Hypoxia PET showed remarkable tracer delivery limitations in the study of vascular disrupting agents but suggested the potential use of PET as a marker of response or resistance to anti-angiogenics. Finally, the effect of anaesthesia on tracer kinetics and tumour oxygenation as well as perfusion dependency in tracer uptake should be carefully evaluated to avoid artefactual results. Conclusions: Preclinical studies highlight the advantages and the limitations of the available hypoxia-radiotracers and their potential usefulness for the evaluation of treatments outcome and radiotherapy planning.
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- 2017
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27. The prognostic value of pimonidazole and tumour pO2 in human cervix carcinomas after radiation therapy: A prospective international multi-center study
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Nordsmark, Marianne, Loncaster, Julie, Aquino-Parsons, Christina, Chou, Shu-Chuan, Gebski, Val, West, Catharine, Lindegaard, Jacob C., Havsteen, Hanne, Davidson, Susan E., Hunter, Robin, Raleigh, James A., and Overgaard, Jens
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TUMORS , *CERVICAL cancer , *RADIOTHERAPY , *CANCER research - Abstract
Abstract: Background and purpose: Hypoxia adversely affects treatment outcome in human uterine cervical cancer. Here, we present the results of a prospective international multi-centre study evaluating the prognostic value of pre-treatment tumour oxygen partial pressure (pO2) and the hypoxia marker pimonidazole (pimo). Materials and methods: One hundred and twenty-seven patients with primary cervix cancer were entered. Pre-treatment tumour pO2 measurements were obtained, and reported by the median tumour pO2, the fraction of pO2 values ⩽10mmHg (HP10), ⩽5mmHg (HP5) and ⩽2.5mmHg (HP2.5). Following intravenous pimonidazole administration, biopsies were taken, stained for pimonidazole adducts, and scored for the area of labelled tumour cells on a scale from 0 to 4. Treatment modalities were surgery (11%), radiotherapy (98%), chemotherapy (33%) and carbogen (14%). Results: None of the hypoxia descriptors were statistically significant prognostic factors for loco-regional tumour control or overall survival when analyzed as continuous variables or divided by the sample median. By univariate analysis only tumour size and nodal status were significant prognostic factors for local control. Tumour size and FIGO stage were significant for overall survival. In a multivariate analysis stratified by centre, only tumour size above 5cm and lower pre-treatment haemoglobin predicted poorer overall survival among FIGO stage, nodal involvement, tumour size, pre-treatment haemoglobin dichotomized at 12g/dl and pimo 1, pimo 4 and HP5 as continuous variables. Conclusion: Neither Eppendorf nor pimonidazole should be dismissed based on the current results. However, further investigations are needed to readdress the hypotheses of the current study having optimized statistical designs, and a population of sufficient size treated more homogenously following rigorous protocols. [Copyright &y& Elsevier]
- Published
- 2006
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28. Correction of anaemia through the use of darbepoetin alfa improves chemotherapeutic outcome in a murine model of Lewis lung carcinoma.
- Author
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Shannon, A. M., Bouchier-Hayes, D. J., Condron, C. M., and Toomey, D.
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LUNG cancer , *CANCER treatment , *ANEMIA , *THERAPEUTICS , *CANCER cells , *SERUM , *CANCER chemotherapy , *BIOLOGICAL models , *RESEARCH , *ANIMAL experimentation , *RESEARCH methodology , *CELL receptors , *ANTINEOPLASTIC agents , *EVALUATION research , *COMPARATIVE studies , *ERYTHROPOIETIN , *MICE , *PHARMACODYNAMICS - Abstract
Darbepoetin alfa (Aranesp), Amgen) is a novel erythropoiesis-stimulating protein with a serum half-life longer than recombinant human erythropoietin (Epo), used in the treatment of cancer-associated anaemia. Anaemia is known to adversely affect prognosis and response to treatment in cancer patients. Solid tumours contain regions of hypoxia due to poor vascular supply and cellular compaction. Although hypoxic stress usually results in cell death, hypoxia-resistant tumour cells are genetically unstable and often acquire a drug-resistant phenotype. Increasing tumour oxygenation and perfusion during treatment could have the doubly beneficial outcome of reducing the fraction of treatment-resistant cells, while increasing drug delivery to previously hypoxic tissue. In this study, we examined the effect of darbepoetin alfa on chemotherapy sensitivity and delivery in an in vivo model of Lewis lung carcinoma, shown here to express the Epo receptor (EpoR). We identified that weekly darbepoetin alfa treatment, commencing 10 days before chemotherapy, resulted in a significant reduction in tumour volume compared to chemotherapy alone. This was mediated by the prevention of anaemia, a reduction in tumour hypoxia and a concomitant increase in drug delivery. Darbepoetin alfa treatment alone did not modulate the growth of the EpoR-expressing tumour cells. This study identifies an important role for darbepoetin alfa in increasing the therapeutic index of chemotherapy. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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29. The impact of anaemia on outcome in cancer.
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Clarke, H. and Pallister, C. J.
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ANEMIA , *HYPOXEMIA , *CANCER , *THERAPEUTICS , *PROGNOSIS , *MEDICAL research - Abstract
Anaemia is not an inconsequential side effect of cancer and its treatment should not be ignored. Current practice for anaemia management varies and its role in influencing outcome in cancer patients is under recognized. As a common complication of cancer, anaemia is prevalent in virtually all tumour types to varying degrees. Predictive factors for anaemia include baseline haemoglobin concentration, decrease in haemoglobin concentration within the first month of treatment, tumour type, duration of treatment and prior blood transfusions. Interest in the prognostic significance of anaemia in cancer patients has generated extensive clinical research. Data is now published in a wide range of tumour types confirming that anaemia is a negative prognostic indicator of outcome (e.g. survival, disease-free recurrence and local relapse), with the strongest association in patients receiving radiotherapy. The association has also been documented in patients undergoing chemotherapy and chemoradiation. A retrospective meta-analysis has shown an overall 65% increased risk of death associated with anaemia in cancer patients. The impact of anaemia as an independent prognostic factor for outcome may be mediated by several factors, however the emerging consensus is on the central role of tumour hypoxia. It has been nearly 50 years since R. Thomlinson and L. Gray (British Journal of Cancer1955,9: 539) first documented the existence of hypoxia in tumours and it is now well accepted that tumour hypoxia protects tumour cells from therapeutic damage directly by reducing the availability of oxygen-free radicals which are necessary for optimal impact of radiotherapy, certain chemotherapeutic agents and photodynamic therapy. The indirect effects include the impact of hypoxia on gene expression, which affects genetic stability, proliferation kinetics and cellular metabolism. There has been an emergence of preclinical and circumstantial data over recent years that are suggestive of the ability to correct the negative effect of anaemia on outcome by the use of repeated blood transfusions or recombinant human erythropoietin. This has led to some attempts to measure the impact on survival in cancer patients of treating anaemia, but early attempts have served to underline the complexity of the relationship and have produced unexpected results. [ABSTRACT FROM AUTHOR]
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- 2005
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30. The Effect of Deep Inspiration Breath-hold on Tumour Oxygenation
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Aquino-Parsons, C., Ries, C.R., Minchinton, A.I., and D’yachkova, Y.
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CANCER patients , *METASTASIS , *OXYGEN therapy , *TUMORS - Abstract
Aim: To investigate the influence of deep inspiration breath-hold on the oxygen tension of in-vivo tumours measured using an Eppendorf pO2histograph.Materials and methods: Patients with accessible primary or metastatic tumours ≥2 cm diameter were entered into a protocol measuring tumour oxygenation with an Eppendorf pO2histograph during normal breathing (NB) and deep inspiration breath-hold (DIBH). Change in oxygen tension was assessed using the Wilcoxon Signed Ranks test.Results: Thirty patients were entered in to this protocol. The median maximum tumour dimension was 4 cm. The median of the median pO2of these tumours was 18 mmHg. Tumours were assessed during NB and DIBH. Oxygen tension measurements along 1–3 pairs of tracks per tumour (median of 2) were obtained. The median number of measurements per track was 30 for NB and 29 for DIBH (range 17–59). In six tumours, the values during NB were significantly higher than during DIBH, whereas, for six other tumours, the relationship was the opposite; for the remaining 18 patients, no significant difference was observed.Conclusion: These data show heterogeneity of tumour oxygenation seen with in-situ tumours both at baseline and as a result of DIBH. No systematic change in the Eppendorf pO2measurements was seen as a result of DIBH; however, the individual tumour responses to DIBH varied dramatically. [Copyright &y& Elsevier]
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- 2003
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31. Measurements of hypoxia using pimonidazole and polarographic oxygen-sensitive electrodes in human cervix carcinomas
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Nordsmark, Marianne, Loncaster, Juliette, Aquino-Parsons, Christina, Chou, Shu-Chuan, Ladekarl, Morten, Havsteen, Hanne, Lindegaard, Jacob C., Davidson, Susan E., Varia, Mahesh, West, Catharine, Hunter, Robin, Overgaard, Jens, and Raleigh, James A.
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TUMORS , *HYPOXEMIA - Abstract
Background and purpose: The measurement of tumour oxygenation using Eppendorf oxygen-sensitive needle electrodes can provide prognostic information but the method is limited to accessible tumours that are suitable for electrode insertion. In this paper the aim was to study the relationship between such physiological measurements of tumour hypoxia and the labelling of tumours with the hypoxia-specific marker pimonidazole.Materials and methods: Assessment of tumour oxygen partial pressure (pO2) using an Eppendorf pO2 histograph and immunohistochemical pimonidazole labelling was carried out in 86 patients with primary cervix carcinomas. Pimonidazole was given as a single injection (0.5 g/m2 i.v.) and 10–24 h later pO2 measurements were made and biopsies taken. Tumour oxygenation status was evaluated as the median tumour pO2 and the fraction of pO2 values ≤10 mmHg (HP10), ≤5 mmHg (HP5) and ≤2.5 mmHg (HP2.5). Hypoxia was detected by immunohistochemistry using monoclonal antibodies directed against reductively activated pimonidazole. Pimonidazole binding was scored using a light microscope. Each tumour was evaluated by the relative area pimonidazole at highest score and the accumulated area of pimonidazole labelling from score 1 to 4. Necrosis was measured in HE stained sections.Results and conclusions: The degree of hypoxia assessed by either pimonidazole binding or invasive electrode measurements varied significantly between tumours. There was a trend that the most hypoxic tumours measured by oxygen electrodes had the highest score of necrosis, and no or little pimonidazole binding. However, this observation was not consistent and there was no correlation between pimonidazole staining expressed in this way and oxygen electrode measurements of hypoxia. [Copyright &y& Elsevier]
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- 2003
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32. BOLD contrast fMRI of whole rodent tumour during air or carbogen breathing using echo-planar imaging at 1.5 T.
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Landuyt, Willy, Hermans, Robert, Bosmans, Hilde, Sunaert, Stefan, Béatse, Eric, Farina, Davide, Meijerink, Martijn, Zhang, Hao, Bogaert, Walter, Lambin, Philippe, Marchal, Guy, Landuyt, W, Hermans, R, Bosmans, H, Sunaert, S, Béatse, E, Farina, D, Meijerink, M, Zhang, H, and Van Den Bogaert, W
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TUMORS ,CYSTS (Pathology) ,ONCOLOGY ,CEREBRAL anoxia ,RESPIRATION ,MAGNETIC resonance imaging - Abstract
The aim of this study was to evaluate the feasibility of functional MR imaging (fMRI) at 1.5 T, exploiting blood oxygenation level-dependent (BOLD) contrast, for detecting changes in whole-tumour oxygenation induced by carbogen (5% CO2+95% O2) inhalation of the host. Adult WAG/Rij rats with rhabdomyosarcomas growing subcutaneously in the lower flank were imaged when tumours reached sizes between 1 and 11 cm3 (n=12). Air and carbogen were alternatively supplied at 2 l/min using a snout mask. Imaging was done on a 1.5-T MR scanner using a T2*-weighted gradient-echo, echo-planar imaging (GE-EPI) sequence. Analysis of the whole-tumour EPI images was based on statistical parametric maps. Voxels with and without signal intensity changes (SIC) were recorded. Significance thresholds were set at p<0.05, corrected for multiple comparisons. In continuous air breathing condition, 3 of 12 tumours showed significant negative SIC and 1 tumour had a clear-cut positive SIC. The remaining tumours showed very little or no change. When switching to carbogen breathing, the SIC were significantly positive in 10 of 12 tumours. Negative SIC were present in 4 tumours, of which three were simultaneously characterised by positive SIC. The overall analysis indicated that 6 of the 12 tumours could be considered as strong positive responders to carbogen. Our research demonstrates the applicability of fMRI GE-EPI at 1.5 T to study whole-tumour oxygenation non-invasively. The observed negative SIC during air condition may reflect the presence of transient hypoxia during these measurements. Selection of tumours on the basis of their individual response to carbogen is possible, indicating a role of such non-invasive measurements for using tailor-made treatments. [ABSTRACT FROM AUTHOR]
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- 2001
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33. Radiation-induced Vascular Damage and the Impact on the Treatment Outcome of Stereotactic Body Radiotherapy
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Maciej Kujawski, Jamison Brooks, Alexandru Dasu, Iuliana Toma-Dasu, Emely Lindblom, and Susanta K. Hui
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Cancer Research ,medicine.medical_specialty ,Treatment outcome ,Radiation induced ,Breast Neoplasms ,Radiosurgery ,Models, Biological ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Cell Line, Tumor ,medicine ,Animals ,Humans ,business.industry ,General Medicine ,Hypoxia (medical) ,Tumour oxygenation ,Cell Hypoxia ,Microscopy, Fluorescence, Multiphoton ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Blood Vessels ,Female ,Radiology ,Dose Fractionation, Radiation ,medicine.symptom ,business ,Stereotactic body radiotherapy ,Neoplasm Transplantation - Abstract
BACKGROUND/AIM: The aim of this study was to investigate radiation-induced tumour vascular damage and its impact thereof on the outcome of stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Vessel densities in animal tumours before and after a single dose of 20 Gy were quantified and used as input for simulations of three-dimensional tumours with heterogeneous oxygenation. SBRT treatments of the modelled tumours in 1–8 fractions were simulated. The impact of vessel collapse on the outcome of SBRT was investigated by calculating tumour control probability (TCP) and the dose required to obtain a TCP of 50% (D(50)). RESULTS: A radiation-induced increase of acute hypoxia in tumours during SBRT treatment could be simulated based on the experimental data. The D(50) values for these tumours were higher than for the simulated tumours without vessel collapse. CONCLUSION: The vascular changes after high doses of radiation could compromise the outcome of SBRT by increasing tumour hypoxia.
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- 2019
34. Radiation-induced Vascular Damage and the Impact on the Treatment Outcome of Stereotactic Body Radiotherapy
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Lindblom, Emely Kjellsson, Hui, Susanta, Brooks, Jamison, Dasu, Alexandru, Kujawski, Maciej, Toma-Dasu, Iuliana, Lindblom, Emely Kjellsson, Hui, Susanta, Brooks, Jamison, Dasu, Alexandru, Kujawski, Maciej, and Toma-Dasu, Iuliana
- Abstract
Background/Aim: The aim of this study was to investigate radiation-induced tumour vascular damage and its impact thereof on the outcome of stereotactic body radiotherapy (SBRT). Materials and Methods: Vessel densities in animal tumours before and after a single dose of 20 Gy were quantified and used as input for simulations of three-dimensional tumours with heterogeneous oxygenation. SBRT treatments of the modelled tumours in 1-8 fractions were simulated. The impact of vessel collapse on the outcome of SBRT was investigated by calculating tumour control probability (TCP) and the dose required to obtain a TCP of 50% (D-50). Results: A radiation-induced increase of acute hypoxia in tumours during SBRT treatment could be simulated based on the experimental data. The D-50 values for these tumours were higher than for the simulated tumours without vessel collapse. Conclusion: The vascular changes after high doses of radiation could compromise the outcome of SBRT by increasing tumour hypoxia.
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- 2019
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35. Hypoxia Induced by Vascular Damage at High Doses Could Compromise the Outcome of Radiotherapy
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Kjellsson Lindblom, Emely, Dasu, Alexandru, Toma-Dasu, Iuliana, Kjellsson Lindblom, Emely, Dasu, Alexandru, and Toma-Dasu, Iuliana
- Abstract
Background/Aim: This study investigated the impact of temporary vascular collapse on tumour control probability (TCP) in stereotactic body radiotherapy (SBRT), taking into account different radiosensitivities of chronically and acutely hypoxic cells. Materials and Methods: Three-dimensional tumours with heterogeneous oxygenation were simulated assuming different fractions of collapsed vessels at every treatment fraction. The modelled tumours contained a chronically hypoxic subvolume of 30-60% of the tumour diameter, and a hypoxic fraction ≤5 mm Hg of 30-50%. The rest of the tumours were well-oxygenated at the start of the simulated treatment. Results: For all simulated cases, the largest reduction in TCP from 97% to 2% was found in a tumour with a small chronically hypoxic core treated with 60 Gy in eight fractions and assuming a treatment-induced vascular collapse of 35% in the well-oxygenated region. Conclusion: The timing of SBRT fractions should be considered together with the tumour oxygenation to avoid loss of TCP in SBRT.
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- 2019
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36. Radiation-induced vascular damage and the impact on the treatment outcome of stereotactic body radiotherapy
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Kjellsson Lindblom, Emely, Hui, Susanta, Brooks, Jamison, Dasu, Alexandru, Kujawski, Maciej, Toma-Dasu, Iuliana, Kjellsson Lindblom, Emely, Hui, Susanta, Brooks, Jamison, Dasu, Alexandru, Kujawski, Maciej, and Toma-Dasu, Iuliana
- Abstract
Background/Aim: The aim of this study was to investigate radiation-induced tumour vascular damage and its impact thereof on the outcome of stereotactic body radiotherapy (SBRT). Materials and Methods: Vessel densities in animal tumours before and after a single dose of 20 Gy were quantified and used as input for simulations of three-dimensional tumours with heterogeneous oxygenation. SBRT treatments of the modelled tumours in 1-8 fractions were simulated. The impact of vessel collapse on the outcome of SBRT was investigated by calculating tumour control probability (TCP) and the dose required to obtain a TCP of 50% (D50). Results: A radiation-induced increase of acute hypoxia in tumours during SBRT treatment could be simulated based on the experimental data. The D50 values for these tumours were higher than for the simulated tumours without vessel collapse. Conclusion: The vascular changes after high doses of radiation could compromise the outcome of SBRT by increasing tumour hypoxia.
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- 2019
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37. Imaging tumour hypoxia with oxygen-enhanced MRI and BOLD MRI
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Simon P. Robinson, James P B O'Connor, and John C. Waterton
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medicine.medical_specialty ,medicine.medical_treatment ,Blood oxygenation level dependent ,Contrast Media ,Review Article ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Carbogen ,Neoplasms ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Tumor hypoxia ,medicine.diagnostic_test ,business.industry ,General Medicine ,Hypoxia (medical) ,Oxygen enhanced ,Tumour oxygenation ,Magnetic Resonance Imaging ,Radiation therapy ,Oxygen ,Positron emission tomography ,Tumor Hypoxia ,Radiology ,medicine.symptom ,business ,Biomarkers - Abstract
Hypoxia is known to be a poor prognostic indicator for nearly all solid tumours and also is predictive of treatment failure for radiotherapy, chemotherapy, surgery and targeted therapies. Imaging has potential to identify, spatially map and quantify tumour hypoxia prior to therapy, as well as track changes in hypoxia on treatment. At present no hypoxia imaging methods are available for routine clinical use. Research has largely focused on positron emission tomography (PET)-based techniques, but there is gathering evidence that MRI techniques may provide a practical and more readily translational alternative. In this review we focus on the potential for imaging hypoxia by measuring changes in longitudinal relaxation [R (1); termed oxygen-enhanced MRI or tumour oxygenation level dependent (TOLD) MRI] and effective transverse relaxation [R (2)*; termed blood oxygenation level dependent (BOLD) MRI], induced by inhalation of either 100% oxygen or the radiosensitising hyperoxic gas carbogen. We explain the scientific principles behind oxygen-enhanced MRI and BOLD and discuss significant studies and their limitations. All imaging biomarkers require rigorous validation in order to translate into clinical use and the steps required to further develop oxygen-enhanced MRI and BOLD MRI into decision-making tools are discussed.
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- 2018
38. Impact of myo-inositol trispyrophosphate (ITPP) on tumour oxygenation and response to irradiation in rodent tumour models
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Arne Heyerick, Bernard Gallez, Thanh-Trang Cao-Pham, Ly-Binh-An Tran, Bénédicte F. Jordan, Sofie Deschoemaeker, Faculty of Economic and Social Sciences and Solvay Business School, and UCL - SSS/LDRI - Louvain Drug Research Institute
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0301 basic medicine ,ITPP ,Erythrocytes ,medicine.medical_treatment ,Inositol Phosphates ,Mice, Nude ,Rodentia ,03 medical and health sciences ,Hemoglobins ,Mice ,0302 clinical medicine ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Irradiation ,Oximetry ,Rhabdomyosarcoma ,radiotherapy ,Mice, Inbred C3H ,Chemistry ,hypoxia ,Therapeutic effect ,Cell Biology ,Oxygenation ,Glioma ,Original Articles ,Tumour oxygenation ,medicine.disease ,oxygen consumption ,In vitro ,Rats, Inbred F344 ,Rats ,EPR oximetry ,Radiation therapy ,Oxygen ,Disease Models, Animal ,030104 developmental biology ,Cell culture ,030220 oncology & carcinogenesis ,Cancer research ,Molecular Medicine ,Original Article - Abstract
Tumour hypoxia is a well‐established factor of resistance in radiation therapy (RT). Myo‐inositol trispyrophosphate (ITPP) is an allosteric effector that reduces the oxygen‐binding affinity of haemoglobin and facilitates the release of oxygen by red blood cells. We investigated herein the oxygenation effect of ITPP in six tumour models and its radiosensitizing effect in two of these models. The evolution of tumour pO2 upon ITPP administration was monitored on six models using 1.2 GHz Electron Paramagnetic Resonance (EPR) oximetry. The effect of ITPP on tumour perfusion was assessed by Hoechst staining and the oxygen consumption rate (OCR) in vitro was measured using 9.5 GHz EPR. The therapeutic effect of ITPP with and without RT was evaluated on rhabdomyosarcoma and 9L‐glioma rat models. ITPP enhanced tumour oxygenation in six models. The administration of 2 g/kg ITPP once daily for 2 days led to a tumour reoxygenation for at least 4 days. ITPP reduced the OCR in six cell lines but had no effect on tumour perfusion when tested on 9L‐gliomas. ITPP plus RT did not improve the outcome in rhabdomyosarcomas. In 9L‐gliomas, some of tumours receiving the combined treatment were cured while other tumours did not benefit from the treatment. ITPP increased oxygenation in six tumour models. A decrease in OCR could contribute to the decrease in tumour hypoxia. The association of RT with ITPP was beneficial for a few 9L‐gliomas but was absent in the rhabdomyosarcomas.
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- 2018
39. Photoacoustic imaging to probe tumour oxygenation and oxidative stress dynamics (Conference Presentation)
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Sarah E. Bohndiek
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Oncology ,medicine.medical_specialty ,business.industry ,Angiogenesis ,Photoacoustic imaging in biomedicine ,Cancer ,Oxygenation ,Hypoxia (medical) ,medicine.disease ,Tumour oxygenation ,medicine.disease_cause ,Unmet needs ,Internal medicine ,medicine ,medicine.symptom ,business ,Oxidative stress - Abstract
Hypoxia, or low oxygen partial pressure, is a common feature of many solid tumours, associated with therapy resistance and poor prognosis for cancer patients. This chemical feature of the tumour microenvironment represents an imbalance of blood oxygen supply and tissue oxygen demand. Given the prognostic significance of hypoxia, there is a clinical unmet need to provide validated, non-invasive, imaging biomarkers that can be used to detect and monitor the spatiotemporal distribution of hypoxia at the point of cancer diagnosis and during treatment. In this talk, I will give an overview of how photoacoustic imaging can address this unmet need, providing examples from both preclinical studies in mouse models of cancer and clinical studies in human patients.
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- 2018
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40. Simultaneous visualization of tumour oxygenation, neovascularization and contrast agent perfusion by real-time three-dimensional optoacoustic tomography
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Subhamoy Mandal, Xosé Luís Deán-Ben, Daniel Razansky, Vasilis Ntziachristos, and Vladimir Ermolayev
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Indocyanine Green ,Pathology ,medicine.medical_specialty ,media_common.quotation_subject ,Contrast Media ,Mice, Nude ,Mammary Neoplasms, Animal ,01 natural sciences ,030218 nuclear medicine & medical imaging ,Photoacoustic Techniques ,010309 optics ,Neovascularization ,03 medical and health sciences ,Imaging, Three-Dimensional ,Oxygen Consumption ,0302 clinical medicine ,0103 physical sciences ,medicine ,Animals ,Humans ,Contrast (vision) ,Radiology, Nuclear Medicine and imaging ,Tomography ,media_common ,Neuroradiology ,Neovascularization, Pathologic ,business.industry ,Ultrasound ,General Medicine ,Tumour oxygenation ,Perfusion ,Cross-Sectional Studies ,Female ,Radiology ,Molecular imaging ,medicine.symptom ,business ,Neoplasm Transplantation ,Biomedical engineering - Abstract
Intravital imaging within heterogenic solid tumours is important for understanding blood perfusion profiles responsible for establishment of multiple parameters within the tumour mass, such as hypoxic and nutrition gradients, cell viability, proliferation and drug response potentials. Herein, we developed a method based on a volumetric multispectral optoacoustic tomography (vMSOT) for cancer imaging in preclinical models and explored its capacity for three-dimensional imaging of anatomic, vascular and functional tumour profiles in real time. In contrast to methods based on cross-sectional (2D) image acquisition as a basis for 3D rendering, vMSOT has attained concurrent observations from the entire tumour volume at 10 volumetric frames per second. This truly four dimensional imaging performance has enabled here the simultaneous assessment of blood oxygenation gradients and vascularization in solid breast tumours and revealed different types of blood perfusion profiles in-vivo. The newly introduced capacity for high-resolution three-dimensional tracking of fast tumour perfusion suggests vMSOT as a powerful method in preclinical cancer research and theranostics. As the imaging setup can be equally operated in both stationary and handheld mode, the solution is readily translatable for perfusion monitoring in a clinical setting. • vMSOT visualizes 3D anatomic, vascular and functional tumour profiles in real time. • Three types of blood perfusion profiles are revealed in breast tumour model. • The method is readily adaptable to operate in a handheld clinical mode.
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- 2015
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41. Measurement of the acute metabolic response to hypoxia in rat tumours in vivo using magnetic resonance spectroscopy and hyperpolarised pyruvate
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Becky A.S. Bibby, Gillian M. Tozer, Tooba Alizadeh, Stephen Metcalf, Emily G. Wholey, Adriana Bucur, Martyn N.J. Paley, L. J. Williams, Samira Kazan, Joanne E. Bluff, and Steven Reynolds
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Magnetic Resonance Spectroscopy ,Fibrosarcoma ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Reaction rate constant ,In vivo ,Pyruvic Acid ,Dynamic nuclear polarisation ,medicine ,Animals ,Radiology, Nuclear Medicine and imaging ,Lactic Acid ,Tumour oxygenation ,Hypoxia ,Carbon Isotopes ,Nuclear magnetic resonance spectroscopy ,Hematology ,Hypoxia (medical) ,equipment and supplies ,medicine.disease ,Lactic acid ,Rats ,Disease Models, Animal ,chemistry ,Oncology ,Radiology Nuclear Medicine and imaging ,030220 oncology & carcinogenesis ,Pyruvate metabolism ,Biophysics ,Pyruvic acid ,medicine.symptom ,human activities - Abstract
Purpose To estimate the rate constant for pyruvate to lactate conversion in tumours in response to a hypoxic challenge, using hyperpolarised 13C1-pyruvate and magnetic resonance spectroscopy. Methods and materials Hypoxic inspired gas was used to manipulate rat P22 fibrosarcoma oxygen tension (pO2), confirmed by luminescence decay of oxygen-sensitive probes. Hyperpolarised 13C1-pyruvate was injected into the femoral vein of anaesthetised rats and slice-localised 13C magnetic resonance (MR) spectra acquired. Spectral integral versus time curves for pyruvate and lactate were fitted to a precursor-product model to estimate the rate constant for tumour conversion of pyruvate to lactate (kpl). Mean arterial blood pressure (MABP) and oxygen tension (ArtpO2) were monitored. Pyruvate and lactate concentrations were measured in freeze-clamped tumours. Results MABP, ArtpO2 and tumour pO2 decreased significantly during hypoxia. kpl increased significantly (p
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- 2015
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42. TNF-alpha and melphalan-based isolated limb perfusion: no evidence supporting the early destruction of tumour vasculature
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Lars Erik Podleska, Lale Umutlu, H de Groot, K Funk, Florian Grabellus, and Georg Taeger
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Adult ,Melphalan ,Pathology ,medicine.medical_specialty ,Cancer Research ,Genetic enhancement ,Medizin ,tumour blood flow ,Hemoglobins ,tumour necrosis factor ,immune system diseases ,Neoplasms ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Antineoplastic Agents, Alkylating ,neoplasms ,Molecular Diagnostics ,Aged ,Aged, 80 and over ,Neovascularization, Pathologic ,Oncogene ,Tumor Necrosis Factor-alpha ,business.industry ,Muscles ,Extremities ,Hyperthermia, Induced ,Middle Aged ,medicine.disease ,Oxygen ,medicine.anatomical_structure ,Oncology ,Regional Blood Flow ,Apoptosis ,Chemotherapy, Cancer, Regional Perfusion ,soft tissue sarcoma ,Cancer cell ,Tumor necrosis factor alpha ,Bone marrow ,Erratum ,Liver cancer ,business ,tumour oxygenation ,medicine.drug ,isolated limb perfusion - Abstract
Background: Isolated limb perfusion with TNF-alpha and melphalan (TM-ILP) is a highly effective treatment for locally advanced tumours of the extremities. Previous research suggests an almost immediate disintegration of the blood supply of the tumour. The aim of the present study was to verify this hypothesis using non-invasive measurements of microvascular perfusion and tissue oxygenation. Methods: A total of 11 patients were included in the study. TM-ILP was performed under mildly hyperthermic conditions (39 °C) in the extremities via proximal vascular access. Capillary-venous microvascular blood flow, haemoglobin level (Hb) and oxygen saturation (SO2) were determined using laser Doppler and white-light spectroscopy, respectively, before TM-ILP and at 30 min, 4 h, 1 day, 4 days, 1 week, 2 weeks and 6 weeks after TM-ILP from tumour and healthy muscle tissues. Results: Blood flow and Hb were mostly higher, whereas SO2 was lower, in tumour tissue compared with muscle tissue. In both tumour and muscle tissues, blood flow significantly increased immediately after TM-ILP and remained elevated for at least 2 weeks, followed by a return to the initial values 6 weeks after the procedure. Conclusion: No signs were found of early destruction of the tumour vasculature. The observations suggest that an inflammatory reaction is one of the key elements of TM-ILP.
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- 2015
43. The effect of modulated electro-hyperthermia on temperature and blood flow in human cervical carcinoma
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Jong-Hun Kim, Dong-Hyu Cho, Sun Young Lee, and Yeon-Hee Han
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0301 basic medicine ,Hyperthermia ,Adult ,Cancer Research ,medicine.medical_specialty ,Physiology ,medicine.medical_treatment ,Uterine Cervical Neoplasms ,03 medical and health sciences ,Mild hyperthermia ,0302 clinical medicine ,Physiology (medical) ,Cervical carcinoma ,Medicine ,Humans ,Aged ,Aged, 80 and over ,Chemotherapy ,business.industry ,Ultrasound ,Temperature ,Blood flow ,Hyperthermia, Induced ,Middle Aged ,Tumour oxygenation ,medicine.disease ,Radiation therapy ,030104 developmental biology ,Regional Blood Flow ,030220 oncology & carcinogenesis ,Female ,Radiology ,business - Abstract
Mild hyperthermia has been known to enhance the response of tumours to radiotherapy or chemotherapy by increasing tumour blood flow, thereby increasing tumour oxygenation or drug delivery. The purpose of this study was to assess the changes in temperature and blood flow in human cervical cancer in response to regional heating with modulated electro-hyperthermia (mEHT).The pelvic area of 20 patients with cervical carcinoma was heated with mEHT. The peri-tumour temperature was measured using an internal organ temperature probe. The tumour blood flow was measured using 3D colour Doppler ultrasound by determining the peak systolic velocity/end-diastolic velocity ratio (S/D ratio) and the resistance index (RI) within blood vessels.The mean peri-tumour temperature was 36.7 ± 0.2 °C before heating and increased to 38.5 ± 0.8 °C at the end of heating for 60 min. The marked declines in RI and S/D values strongly demonstrated that heating significantly increased tumour blood perfusion.Regional heating of the pelvic area with mEHT significantly increased the peri-tumour temperature and improved the blood flow in cervical cancer. This is the first demonstration that the blood flow in cervical cancer is increased by regional hyperthermia. Such increases in temperature and blood flow may account for the clinical observations that hyperthermia improves the response of cervical cancer to radiotherapy or chemotherapy.
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- 2018
44. Mathematical Description of Changes in Tumour Oxygenation from Repeated Functional Imaging
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M. Lazzeroni, Dimos Baltas, Anca L. Grosu, Iuliana Toma-Dasu, Alexandru Dasu, and H. Bunea
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medicine.medical_specialty ,Future studies ,Tumor hypoxia ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Oxygenation ,Hypoxia (medical) ,Tumour oxygenation ,030218 nuclear medicine & medical imaging ,Functional imaging ,Radiation therapy ,03 medical and health sciences ,0302 clinical medicine ,Positron emission tomography ,030220 oncology & carcinogenesis ,medicine ,Radiology ,medicine.symptom ,business - Abstract
Functional imaging of tumour hypoxia has been suggested as a tool for refining target definition and treatment optimization in radiotherapy. The approach, however, has been slow to be adopted clinically as most of the studies on the topic do not take into account the in-treatment changes of hypoxia. The present study aimed to introduce a function that quantifies the changes of oxygen distributions in repeated PET images taken during treatment. The proposed approach for determining the reoxygenation function was tested for feasibility on patients with head and neck cancer, repeatedly imaged with FMISO PET during radiotherapy. Reoxygenation functions were derived by solving the convolution between functions describing the oxygen distributions of successive images. The method was found to be mathematically feasible. The results indicate that the reoxygenation functions describing the change in oxygenation have distinct shapes prompting the hypothesis that oxygenation changes reflected by them might have predictive power for treatment outcome. Future studies on a larger patient population to search for predictive correlations based on the reoxygenation function are planned.
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- 2018
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45. Optimal dose and fraction number in SBRT of lung tumours: A radiobiological analysis
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Stefania Naccarato, Ruggero Ruggieri, Nadejda Stavreva, Filippo Alongi, Alan E. Nahum, and Pavel Stavrev
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Oncology ,medicine.medical_specialty ,Pathology ,Lung Neoplasms ,Stereotactic body radiation therapy ,Population ,Biophysics ,General Physics and Astronomy ,Dose distribution ,NSCLC ,Radiosurgery ,030218 nuclear medicine & medical imaging ,Physics and Astronomy (all) ,03 medical and health sciences ,0302 clinical medicine ,Therapeutic index ,Fraction number ,Nuclear Medicine and Imaging ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,SBRT ,TCP ,Neoplasm Staging ,Radiobiology ,Dose Fractionation ,Radiology, Nuclear Medicine and Imaging ,Non-Small-Cell Lung ,education ,education.field_of_study ,business.industry ,Carcinoma ,General Medicine ,Tumour oxygenation ,Homogeneous ,030220 oncology & carcinogenesis ,Dose Fractionation, Radiation ,Lung tumours ,Radiology ,business - Abstract
The efficacy of Stereotactic Body Radiation Therapy (SBRT) in early-stage non-small cell lung cancer for severely hypofractionated schedules is clinically proven. Tumour control probability (TCP) modelling might further optimize prescription dose and number of treatment fractions (n). To this end, we will discuss the following controversial questions. Which is the most plausible cell-survival model at doses per fraction (d) as high as 20Gy? Do clinical data support a dose-response relationship with saturation over some threshold-dose? Given the reduced re-oxygenation for severe hypofractionation, is the inclusion of tumour hypoxia in TCP modelling relevant? Can iso-effective schedules be derived by assuming a homogeneous tumour-cell population with α/β≈10Gy, or should distinct cell subpopulations, with different α/β values, be taken into account? Is there scope for patient-specific individualization of n? Despite the difficulty of providing definite answers to the above questions, reasonable suggestions for lung SBRT can be derived from the literature. The LQ model appears to be the best-fitting model of cell-survival even at such large d, and is therefore the preferred choice for TCP modelling. TCP increases with dose, reaching saturation above 90% local control, but there is still uncertainty on the threshold-dose. In silico simulations accounting for variations in tumour oxygenation are consistent with an improved therapeutic ratio at 5-8 fractions instead of the current 3-fraction reference schedules. Tumour hypoxia modelling might also explain how α/β changes with n, identifying the clonogen subpopulation which determines tumour response. Finally, an optimal patient-specific n can be derived from the planned lung dose distribution.
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- 2016
46. Impact of hyperthermic isolated limb perfusion on tumour oxygenation in soft tissue sarcoma
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Peter Hohenberger, Inez von Rege, Christel Weiss, and Jens Jakob
- Subjects
Adult ,Male ,Melphalan ,Cancer Research ,Pathology ,medicine.medical_specialty ,Necrosis ,Adolescent ,Physiology ,Locally advanced ,Soft Tissue Neoplasms ,Body Temperature ,Upper Extremity ,Young Adult ,Physiology (medical) ,medicine ,Humans ,Antineoplastic Agents, Alkylating ,Aged ,Aged, 80 and over ,Isolated limb perfusion ,Tumor Necrosis Factor-alpha ,business.industry ,Soft tissue sarcoma ,Sarcoma ,Hyperthermia, Induced ,Middle Aged ,Tumour oxygenation ,medicine.disease ,Combined Modality Therapy ,Oxygen ,Catheter ,Lower Extremity ,Chemotherapy, Cancer, Regional Perfusion ,Female ,Tumor necrosis factor alpha ,medicine.symptom ,business ,Nuclear medicine ,medicine.drug - Abstract
Hyperthermic isolated limb perfusion (ILP) with recombinant tumour necrosis factor alpha (TNF) and melphalan contributes to limb-saving treatment in patients with locally advanced extremity soft tissue sarcoma (STS). This study was conducted to evaluate the dynamic changes of tumour oxygenation and temperature during ILP and their effects on treatment response.Tumour oxygenation (pO(2)) and tumour temperature were measured by intratumourally placed O(2)-sensitive catheter electrodes in 34 patients who underwent ILP for locally advanced or recurrent STS. Tumour response to ILP was assessed by the fraction of tumour necrosis in the resection specimen.Mean tumour pO(2) prior to application of TNF and melphalan was 36 mm Hg (range: 2-116 mm Hg) and dropped significantly to 13 mm Hg (range: 0-67 mm Hg, p = 0.03) during ILP. Mean tumour tissue temperature increased from 34.4°C (range 32.4-36.4) to 38.5°C (range 34.1-40.4, p = 0.0001). The mean fraction of necrosis in the resection specimen was 65% (range 5-99). Only the tumour tissue temperature at the onset of ILP correlated with the extent of tumour necrosis (p = 0.01).ILP with TNF and melphalan induces severe oxygen deprivation in soft tissue sarcoma. However, changes in tumour oxygenation did not correlate with treatment response.
- Published
- 2012
- Full Text
- View/download PDF
47. DCE-MRI: a review and applications in veterinary oncology
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Donald E. Thrall, M. Keara Boss, and Naira Muradyan
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medicine.medical_specialty ,General Veterinary ,medicine.diagnostic_test ,business.industry ,Cancer ,Magnetic resonance imaging ,Veterinary oncology ,medicine.disease ,Tumour oxygenation ,Treatment efficacy ,Functional imaging ,Tumour perfusion ,medicine ,Quantitative assessment ,Radiology ,skin and connective tissue diseases ,business - Abstract
Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is a functional imaging technique that assesses the physiology of tumour tissue by exploiting abnormal tumour microvasculature. Advances made through DCE-MRI include improvement in the diagnosis of cancer, optimization of treatment choices, assessment of treatment efficacy and non-invasive identification of prognostic information. DCE-MRI enables quantitative assessment of tissue vessel density, integrity, and permeability, and this information can be applied to study of angiogenesis, hypoxia and the evaluation of various biomarkers. Reproducibility of DCE-MRI results is important in determining the significance of observed changes in the parameters. As improvements are made towards the utility of DCE-MRI and interpreting biologic associations, the technique will be applied more frequently in the study of cancer in animals. Given the importance of tumour perfusion with respect to tumour oxygenation and drug delivery, the use of DCE-MRI is a convenient and powerful way to gain basic information about a tumour.
- Published
- 2011
- Full Text
- View/download PDF
48. The hypoxic tumour microenvironment, patient selection and hypoxia-modifying treatments
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Henri A. M. Marres, Ilse J. Hoogsteen, A.J. van der Kogel, and Johannes H.A.M. Kaanders
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Niacinamide ,Oncology ,Radiation-Sensitizing Agents ,medicine.medical_specialty ,Pathology ,medicine.medical_treatment ,Treatment outcome ,Radiation Tolerance ,Translational research [ONCOL 3] ,Neoplasms ,Internal medicine ,Perception and Action [DCN 1] ,Biomarkers, Tumor ,Quantitative assessment ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Hyperbaric Oxygenation ,Chemotherapy ,business.industry ,Patient Selection ,Neoplasms therapy ,Anemia ,Carbon Dioxide ,Hypoxia (medical) ,Tumour oxygenation ,Cell Hypoxia ,Tumor microenvironment [UMCN 1.3] ,Oxygen ,Vitamin B Complex ,Treatment strategy ,Nuclear Medicine ,medicine.symptom ,business ,Functional Neurogenomics [DCN 2] - Abstract
Contains fulltext : 51464.pdf (Publisher’s version ) (Closed access) Tumour hypoxia has been found to be a characteristic feature in many solid tumours. It has been shown to decrease the therapeutic efficacy of radiation treatment, surgery and some forms of chemotherapy. Successful approaches have been developed to counteract this resistance mechanism, although usually at the cost of increased short- and long-term side-effects. New methods for qualitative and quantitative assessment of tumour oxygenation have made it possible to establish the prognostic significance of tumour hypoxia. The ability to determine the degree and extent of hypoxia in solid tumours is not only important prognostically, but also in the selection of patients for hypoxia-modifying treatments. To provide the best attainable quality of life for individual patients it is of increasing importance that tools be developed that allow a better selection of patients for these intensified treatment strategies. Several genes and proteins involved in the response to hypoxia have been identified as potential candidates for future use in predictive assays. Although some markers and combinations have shown potential benefit and are associated with treatment outcome, their clinical usefulness needs to be validated in prospective trials. A review of published studies was carried out, focusing on the assessment of tumour hypoxia, patient selection and the possibilities to overcome hypoxia during treatment.
- Published
- 2007
49. Pre-radiotherapy Haemoglobin Level is A Prognosticator in Locally Advanced Head and Neck Cancers Treated with Concurrent Chemoradiation
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A N Vaidhyswaran, Karthikeyan Perumal, Mahadev Potharaju, and Rajesh Kar Narayanaswamy
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haemoglobin concentration ,medicine.medical_specialty ,Blood transfusion ,medicine.medical_treatment ,Clinical Biochemistry ,lcsh:Medicine ,Oncology Section ,law.invention ,Randomized controlled trial ,law ,Statistical significance ,Internal medicine ,medicine ,Mucositis ,Clinical endpoint ,Performance status ,business.industry ,hypoxia ,lcsh:R ,General Medicine ,medicine.disease ,Head and neck squamous-cell carcinoma ,oxygen transport capacity ,Surgery ,Radiation therapy ,business ,tumour oxygenation - Abstract
Introduction: Radiation plays a major role in treatment of locoregional control of Head and Neck Squamous cell carcinoma (HNSCC). Anaemia is considered a contributor to intra-tumour hypoxia and tumour resistance to ionizing radiation and most evidences are from developed world, we prospectively investigated the exact role of anaemia in treatment outcome of Stage III/IVA HNSCC in our patient population. Aim of the Study: Primary end point: To analyse the PreRadiotherapy haemoglobin level and early response of treatment in stage III/IVA HNSCC and to determine the relationship of Pre-Radiotherapy haemoglobin level with other prognostic factors. Materials and Methods: This non-interventional single blinded randomized study enrolled patients attending the OPD consecutively, who met our eligibility criteria. Inclusion Criteria: HNSCC patients of Stage III/IVA aged ≥18 years and ≤ 70 years with ECOG status of 1or 2 and willing for concurrent chemoradiation and at least 6 weeks of follow up. Exclusion Criteria: 1) Previous history of treatment for malignancy or radiation in head and neck site. 2) Patients with other fatal and non-fatal pre-morbid or co-morbid conditions that can affect the outcome or the overall survival. Patients with Pre-radiotherapy haemoglobin status < 10 g/dl were given haematinic support and/or blood transfusion. All patients received concurrent chemotherapy (weekly cisplatin) and radiation in conventionally fractionated dose of 66Gy. Early treatment responses were evaluated with Revised RECIST version 1.1 and Data analysis using SPSS version 17.0. Results: Ninety one patients enrolled had mean age of 55.63 (range: 32-69), a median of 56 and mode of 60. Seventy one were males (78%) and 20 females (22%) with a performance status of ECOG 1 in 43 (47%) patients and ECOG 2 in 48 (53%); Pre-RT Hb level of 5 days (p = 5 days and nondevelopment of grade III mucositis was found to be significantly associated with good loco-regional control. Haemoglobin level ≥10.7 g/dl was associated with better treatment outcome, higher performance status, fewer treatment interruptions and lesser degree of mucositis. Transfusion did not affect the outcome. Definitive conclusions and recommendations need further expansion of our study for better statistical power.
- Published
- 2015
50. The Factors Affecting Tumour Oxygenation
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G. Froese
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Medicine ,business ,Tumour oxygenation - Published
- 2015
- Full Text
- View/download PDF
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