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Toma-Dasu, I., Uhrdin, J., Lazzeroni, M., Carvalho, S., van Elmpt, W., Lambin, P. & Dasu, A. (2015). Evaluating tumor response of non-small cell lung cancer patients with 18F-fludeoxyglucose positron emission tomography: potential for treatment individualization. International Journal of Radiation Oncology, Biology, Physics, 91(2), 376-384
Open this publication in new window or tab >>Evaluating tumor response of non-small cell lung cancer patients with 18F-fludeoxyglucose positron emission tomography: potential for treatment individualization
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2015 (English)In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 91, no 2, p. 376-384Article in journal (Refereed) Published
Abstract [en]

Objective: To assess early tumor responsiveness and the corresponding effective radiosensitivity for individual patients with non-small cell lung cancer (NSCLC) based on 2 successive 18F-fludeoxyglucose positron emission tomography (FDG-PET) scans.

Methods and Materials: Twenty-six NSCLC patients treated in Maastricht were included in the study. Fifteen patients underwent sequential chemoradiation therapy, and 11 patients received concomitant chemoradiation therapy. All patients were imaged with FDG before the start and during the second week of radiation therapy. The sequential images were analyzed in relation to the dose delivered until the second image. An operational quantity, effective radiosensitivity, αeff, was determined at the voxel level. Correlations were sought between the average αeff or the fraction of negative αeff values and the overall survival at 2 years. Separate analyses were performed for the primary gross target volume (GTV), the lymph node GTV, and the clinical target volumes (CTVs).

Results: Patients receiving sequential treatment could be divided into responders and nonresponders, using a threshold for the average αeff of 0.003 Gy-1 in the primary GTV, with a sensitivity of 75% and a specificity of 100% (P<.0001). Choosing the fraction of negative αeff as a criterion, the threshold 0.3 also had a sensitivity of 75% and a specificity of 100% (P<.0001). Good prognostic potential was maintained for patients receiving concurrent chemotherapy. For lymph node GTV, the correlation had low statistical significance. A cross-validation analysis confirmed the potential of the method.

Conclusions: Evaluation of the early response in NSCLC patients showed that it is feasible to determine a threshold value for effective radiosensitivity corresponding to good response. It also showed that a threshold value for the fraction of negative αeff could also be correlated with poor response. The proposed method, therefore, has potential to identify candidates for more aggressive strategies to increase the rate of local control and also avoid exposing to unnecessary aggressive therapies the majority of patients responding to standard treatment.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-113350 (URN)10.1016/j.ijrobp.2014.10.012 (DOI)000348045400019 ()25636761 (PubMedID)
Note

Supported by the QuIC-ConCePT project, which is partly funded by EFPI A companies and the Innovative Medicine Initiative Joint Undertaking under Grant Agreement No. 115151; the National Institute of Health (NIH-USA U01 CA 143062-01, Radiomics of NSCLC); EU 7th framework program (EURECA, ARTFORCE); euroCAT (IVA Interreg - www.eurocat.info); Kankeronderzoekfonds Limburg from the Health Foundation Limburg and the Dutch Cancer Society (KWF UM 2009-4454, KWF MAC 2013-6425); and the Cancer Research Funds of Radiumhemmet.

Available from: 2015-01-16 Created: 2015-01-16 Last updated: 2017-12-05
Dasu, A. & Toma-Dasu, I. (2015). Impact of increasing irradiation time on the treatment of prostate cancers. In: Jaffray David A. (Ed.), World Congress on Medical Physics and Biomedical Engineering, June 7-12, 2015, Toronto, Canada: . Paper presented at World Congress on Medical Physics and Biomedical Engineering (pp. 490-493). Springer, 51
Open this publication in new window or tab >>Impact of increasing irradiation time on the treatment of prostate cancers
2015 (English)In: World Congress on Medical Physics and Biomedical Engineering, June 7-12, 2015, Toronto, Canada / [ed] Jaffray David A., Springer, 2015, Vol. 51, p. 490-493Conference paper, Published paper (Refereed)
Abstract [en]

This study aimed to investigate the expected impact of intrafraction repair during increasing irradiation times for the treatment of prostate cancers. Lengthy sessions are indeed expected for some advanced irradiation techniques capable to deliver the large fractional doses required by the increased fractionation sensitivity of the prostates. For this purpose, clinically-derived parameters characterizing repair rates and dose response curves for prostate tumors have been used to calculate the expected loss of effectiveness when increasing the irradiation time. The results have shown that treatment sessions lasting more than about 20 to 40 minutes could reduce the probability of biochemical control of prostate tumors by more than 20 to 30 percentage points. These results are in agreement with some observed clinical results and therefore they suggest that treatment durations in prostate radiation therapy should be carefully recorded in order to explicitly account for intrafraction repair, especially when irradiation techniques make use of multiple beams and imaging sessions. Failure to do so might overestimate the expected effectiveness of the treatment and could lead to disappointing clinical results precisely from the demanding treatment modalities expected to increase the therapeutic gain in prostate radiotherapy.

Place, publisher, year, edition, pages
Springer, 2015
Series
IFMBE Proceedings, ISSN 1680-0737 ; 51
Keywords
prostate cancer, external beam radiotherapy, hypofractionation, intra-fraction repair
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-120262 (URN)10.1007/978-3-319-19387-8_120 (DOI)000381813000120 ()978-3-319-19387-8 (ISBN)978-3-319-19386-1 (ISBN)
Conference
World Congress on Medical Physics and Biomedical Engineering
Available from: 2015-07-22 Created: 2015-07-22 Last updated: 2017-12-18
Lindblom, E., Dasu, A. & Toma-Dasu, I. (2015). Optimal fractionation in radiotherapy for non-small cell lung cancer - a modelling approach. Acta Oncologica, 54(9), 1592-1598
Open this publication in new window or tab >>Optimal fractionation in radiotherapy for non-small cell lung cancer - a modelling approach
2015 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 9, p. 1592-1598Article in journal (Refereed) Published
Abstract [en]

Background. Conventionally fractionated radiotherapy (CFRT) has proven ineffective in treating non-small cell lung cancer while more promising results have been obtained with stereotactic body radiotherapy (SBRT). Hypoxic tumours, however, might present a challenge to extremely hypofractionated schedules due to the decreased possibility for inter-fraction fast reoxygenation. A potentially successful compromise might be found in schedules employing several fractions of varying fractional doses. In this modelling study, a wide range of fractionation schedules from single-fraction treatments to heterogeneous, multifraction schedules taking into account repair, repopulation, reoxygenation and radiosensitivity of the tumour cells, has been explored with respect to the probability of controlling lung tumours.

Material and methods. The response to radiation of tumours with heterogeneous spatial and temporal oxygenation was simulated including the effects of accelerated repopulation and intra-fraction repair. Various treatments with respect to time, dose and fractionation were considered and the outcome was estimated as Poisson-based tumour control probability for local control.

Results. For well oxygenated tumours, heterogeneous fractionation could increase local control while hypoxic tumours are not efficiently targeted by such treatments despite reoxygenation. For hypofractionated treatments employing large doses per fraction, a synergistic effect was observed between intra-fraction repair and inter-fraction fast reoxygenation of the hypoxic cells as demonstrated by a reduction in D50 from 53.3 Gy for 2 fractions to 52.7 Gy for 5 fractions.

Conclusions. For well oxygenated tumours, heterogeneous fractionation schedules could increase local control rates substantially compared to CFRT. For hypoxic tumours, SBRT-like hypofractionated schedules might be optimal despite the increased risk of intra-fraction repair due to a synergistic effect with inter-fraction reoxygenation.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-120307 (URN)10.3109/0284186X.2015.1061207 (DOI)000366674700049 ()26217986 (PubMedID)
Available from: 2015-07-28 Created: 2015-07-28 Last updated: 2017-12-04
Fowler, J. F., Dasu, A. & Toma-Dasu, I. (2015). Optimum overall treatment time in radiation oncology. Madison, Wisconsin: Medical Physics Publishing
Open this publication in new window or tab >>Optimum overall treatment time in radiation oncology
2015 (English)Book (Refereed)
Abstract [en]

John "Jack" Fowler has been a busy radiation biology researcher and teacher. He has written 581 papers over the last 65 plus years. He has also received nearly every honor the medical physics field can bestow. But Jack is not done. He says it is time he wrote a book. Jack's new book, Optimum overall treatment time in radiation oncology, sums up the key concepts relating to optimum fractionation in radiation therapy that have interested him all these years.

Place, publisher, year, edition, pages
Madison, Wisconsin: Medical Physics Publishing, 2015. p. 93
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-112889 (URN)978-19-3052-473-6 (ISBN)978-19-305-2474-3 (ISBN)
Available from: 2014-12-19 Created: 2014-12-19 Last updated: 2015-05-07
Marcu, L. G., Bezak, E., Toma-Dasu, I. & Dasu, A. (2015). Predictive models of tumour response to treatment using functional imaging techniques. Computational & Mathematical Methods in Medicine, 2015, Article ID 571351
Open this publication in new window or tab >>Predictive models of tumour response to treatment using functional imaging techniques
2015 (English)In: Computational & Mathematical Methods in Medicine, ISSN 1748-670X, E-ISSN 1748-6718, Vol. 2015, p. Article ID 571351-Article in journal, Editorial material (Other academic) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-112756 (URN)10.1155/2015/571351 (DOI)000352877300001 ()
Available from: 2014-12-14 Created: 2014-12-14 Last updated: 2017-12-05
Antonovic, L., Dasu, A., Furusawa, Y. & Toma-Dasu, I. (2015). Relative clinical effectiveness of carbon ion radiotherapy: theoretical modelling for H&N tumours. Journal of radiation research, 56(4), 639-645
Open this publication in new window or tab >>Relative clinical effectiveness of carbon ion radiotherapy: theoretical modelling for H&N tumours
2015 (English)In: Journal of radiation research, ISSN 0449-3060, E-ISSN 1349-9157, Vol. 56, no 4, p. 639-645Article in journal (Refereed) Published
Abstract [en]

Comparison of the efficiency of photon and carbon ion radiotherapy (RT) administered with the same number of fractions might be of limited clinical interest, since a wide range of fractionation patterns are used clinically today. Due to advanced photon treatment techniques, hypofractionation is becoming increasingly accepted for prostate and lung tumours, whereas patients with head and neck tumours still benefit from hyperfractionated treatments. In general, the number of fractions is considerably lower in carbon ion RT. A clinically relevant comparison would be between fractionation schedules that are optimal within each treatment modality category. In this in silico study, the relative clinical effectiveness (RCE) of carbon ions was investigated for human salivary gland tumours, assuming various radiation sensitivities related to their oxygenation. The results indicate that, for hypoxic tumours in the absence of reoxygenation, the RCE (defined as the ratio of D50 for photons to carbon ions) ranges from 3.5 to 5.7, corresponding to carbon ion treatments given in 36 and 3 fractions, respectively, and 30 fractions for photons. Assuming that interfraction local oxygenation changes take place, results for RCE are lower than that for an oxic tumour if only a few fractions of carbon ions are used. If the carbon ion treatment is given in more than 12 fractions, the RCE is larger for the hypoxic than for the well-oxygenated tumour. In conclusion, this study showed that in silico modelling enables the study of a wide range of factors in the clinical considerations and could be an important step towards individualisation of RT treatments.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-116625 (URN)10.1093/jrr/rrv016 (DOI)000360990700005 ()
Note

Funding text: Radiumhemmets Forskningsfonder; Radiumhemmets Forskningsfonder, Stockholm, Sweden

Available from: 2015-03-27 Created: 2015-03-27 Last updated: 2017-12-04
Toma-Dasu, I., Hedman, M. & Dasu, A. (2015). The value of individual measurements for tumor control probability predictions in head and neck patients. In: Jaffray David A. (Ed.), World Congress on Medical Physics and Biomedical Engineering, June 7-12, 2015, Toronto, Canada: . Paper presented at World Congress on Medical Physics and Biomedical Engineering (pp. 1675-1678). Springer, 51
Open this publication in new window or tab >>The value of individual measurements for tumor control probability predictions in head and neck patients
2015 (English)In: World Congress on Medical Physics and Biomedical Engineering, June 7-12, 2015, Toronto, Canada / [ed] Jaffray David A., Springer, 2015, Vol. 51, p. 1675-1678Conference paper, Published paper (Refereed)
Abstract [en]

In the age of personalized cancer medicine, individual measurements of in vitro radiosensitivity and proliferation parameters have great potential for predicting treatment outcome. However, cellular radiosensitivity is quite heterogeneous and therefore concerns exist towards its impact on treatment predictions. It was therefore the purpose of this study to investigate this aspect. Individually-determined radiosensitivities and potential doubling times, as well as tumor volumes from 46 head-and-neck carcinomas treated with radiotherapy, were used to predict tumor control probabilities (TCP) under various biologically-relevant assumptions for heterogeneity in radiosensitivity. TCP predictions were then compared to clinical local control using a ROC curve analysis. The analysis showed that TCP calculated under the assumption of heterogeneous radiosensitivity have the same power of distinguishing between patients with or without local control as from single values for the radiobiological parameters (a sensitivity of 66% and a specificity of 80% for an area under the curve of 0.69). The only difference was in the discrimination criterion (TCP>93% for single parameters and TCP>65% for heterogeneous parameters), illustrating the difference in appearance of the TCP curve under the assumption of heterogeneity. Nevertheless, the results showed that individually determined radiobiological parameters could be quite effective towards predicting treatment outcome for individual patients.

Place, publisher, year, edition, pages
Springer, 2015
Series
IFMBE Proceedings, ISSN 1680-0737
Keywords
radiosensitivity, potential doubling time, head-and-neck carcinomas, TCP
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-120263 (URN)10.1007/978-3-319-19387-8_407 (DOI)000381813000407 ()978-3-319-19387-8 (ISBN)978-3-319-19386-1 (ISBN)
Conference
World Congress on Medical Physics and Biomedical Engineering
Available from: 2015-07-22 Created: 2015-07-22 Last updated: 2017-12-18
Marcu, L. G., Toma-Dasu, I. & Dasu, A. (2015). The six Rs of head and neck cancer radiotherapy. In: Loredana G. Marcu (Ed.), Contemporary Issues in Head and Neck Cancer Management: (pp. 35-58). Rijeka: InTech
Open this publication in new window or tab >>The six Rs of head and neck cancer radiotherapy
2015 (English)In: Contemporary Issues in Head and Neck Cancer Management / [ed] Loredana G. Marcu, Rijeka: InTech , 2015, p. 35-58Chapter in book (Refereed)
Abstract [en]

While the management of head and neck cancer has evolved over the last few decades, there are still several challenges and unanswered questions that need solutions. This book is a small compilation of some topical aspects regarding head and neck cancer treatment, including the etiology of HPV-positive oropharyngeal cancers and risk factors in the young population, the challenge of surgical margin definition and the perennial problem of systemic treatment due to distant metastases. Radiobiological aspects are also covered through the Rs of radiotherapy, with a couple of chapters being dedicated to radioresistance and tumour microenvironment. Contemporary Issues in Head and Neck Cancer Management comes as an addition to the existing literature that aims to tackle this radiobiologically challenging tumour.

Place, publisher, year, edition, pages
Rijeka: InTech, 2015
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-120100 (URN)10.5772/58653 (DOI)978-953-51-2135-0 (ISBN)
Available from: 2015-07-08 Created: 2015-07-08 Last updated: 2015-08-21
Toma-Dasu, I. & Dasu, A. (2015). Towards multidimensional radiotherapy: key challenges for treatment individualisation. Computational & Mathematical Methods in Medicine, 2015, Article ID 934380
Open this publication in new window or tab >>Towards multidimensional radiotherapy: key challenges for treatment individualisation
2015 (English)In: Computational & Mathematical Methods in Medicine, ISSN 1748-670X, E-ISSN 1748-6718, Vol. 2015, p. Article ID 934380-Article, review/survey (Refereed) Published
Abstract [en]

Functional and molecular imaging of tumours have offered the possibility of redefining the target in cancer therapy and individualising the treatment with a multidimensional approach that aims to target the adverse processes known to impact negatively upon treatment result. Following the first theoretical attempts to include imaging information into treatment planning, it became clear that the biological features of interest for targeting exhibit considerable heterogeneity with respect to magnitude, spatial, and temporal distribution, both within one patient and between patients, which require more advanced solutions for the way the treatment is planned and adapted. Combining multiparameter information from imaging with predictive information from biopsies and molecular analyses as well as in treatment monitoring of tumour responsiveness appears to be the key approach to maximise the individualisation of treatment. This review paper aims to discuss some of the key challenges for incorporating into treatment planning and optimisation the radiobiological features of the tumour derived from pretreatment PET imaging of tumour metabolism, proliferation, and hypoxia and combining them with intreatment monitoring of responsiveness and other predictive factors with the ultimate aim of individualising the treatment towards the maximisation of response.

Place, publisher, year, edition, pages
Taylor & Francis, 2015
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-110310 (URN)10.1155/2015/934380 (DOI)000352370300001 ()
Available from: 2014-09-06 Created: 2014-09-06 Last updated: 2017-12-05
Dasu, A. & Toma-Dasu, I. (2015). Will intrafraction repair have negative consequences on extreme hypofractionation in prostate radiation therapy?. British Journal of Radiology, 88(1056), Article ID 20150588
Open this publication in new window or tab >>Will intrafraction repair have negative consequences on extreme hypofractionation in prostate radiation therapy?
2015 (English)In: British Journal of Radiology, ISSN 0007-1285, E-ISSN 1748-880X, Vol. 88, no 1056, p. Article ID 20150588-Article in journal (Refereed) Published
Abstract [en]

Objective: The aim of the present study was to investigate the impact of increasing fraction delivery time on the outcome of hypofractionated radiation therapy for prostate cancer.

Methods: Monoexponential and biexponential repair models have been used for patients with prostate cancer to study the loss of biochemical control at 5 years for several clinically relevant irradiation times. The theoretical predictions were compared with newly reported clinical results from 4607 patients undergoing conventionally fractionated and hypofractionated prostate radiation therapy.

Results: Time-demanding irradiation techniques appear to lead to biochemical control rates that sometimes are about 10–20 percentage points below predictions that neglect intrafraction repair. This difference appears to be of the same order of magnitude as that predicted by moderately slow to slow repair taking place during the irradiation time. The impact is largest for the patient risk groups receiving doses corresponding to the steepest part of the dose–response curve. By contrast, for treatment techniques requiring irradiation times shorter than about 20 min, the impact of intrafraction repair appears to be much smaller and probably difficult to be observed in the light of other sources of uncertainty in clinical data.

Conclusion: Neglecting intrafraction repair might overestimate the effectiveness of some treatment schedules and could also influence any subsequent estimations of fractionation sensitivity for prostate tumours.

Advances in knowledge: The effect of intrafraction repair for prostate cancer should be taken into account for long irradiation sessions as might be expected from scanned beams and/or from multiple intrafraction imaging sessions to check the positioning of the patient.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-121847 (URN)10.1259/bjr.20150588 (DOI)000366681800020 ()26449127 (PubMedID)
Note

Funding agencies: ALF Grants, Region Ostergotland; Cancer Research Funds, Radiumhemmet

Available from: 2015-10-09 Created: 2015-10-09 Last updated: 2017-12-01
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-7101-240X

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