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Johansson, Bengt
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Widmark, A., Gunnlaugsson, A., Beckman, L., Thellenberg-Karlsson, C., Hoyer, M., Lagerlund, M., . . . Nilsson, P. (2019). Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial. The Lancet, 394(10196), 385-395
Open this publication in new window or tab >>Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial
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2019 (English)In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 394, no 10196, p. 385-395Article in journal (Refereed) Published
Abstract [en]

Background: Hypofractionated radiotherapy for prostate cancer has gained increased attention due to its proposed high radiation-fraction sensitivity. Recent reports from studies comparing moderately hypofractionated and conventionally fractionated radiotherapy support the clinical use of moderate hypofractionation. To date, there are no published randomised studies on ultra-hypofractionated radiotherapy. Here, we report the outcomes of the Scandinavian HYPO-RTPC phase 3 trial with the aim to show non-inferiority of ultra-hypofractionation compared with conventional fractionation.

Methods: In this open-label, randomised, phase 3 non-inferiority trial done in 12 centres in Sweden and Denmark, we recruited men up to 75 years of age with intermediate-to-high-risk prostate cancer and a WHO performance status between 0 and 2. Patients were randomly assigned to ultra-hypofractionation (42.7 Gy in seven fractions, 3 days per week for 2.5 weeks) or conventional fractionated radiotherapy (78.0 Gy in 39 fractions, 5 days per week for 8 weeks). No androgen deprivation therapy was allowed. The primary endpoint was time to biochemical or clinical failure, analysed in the per-protocol population. The prespecified non-inferiority margin was 4% at 5 years, corresponding to a critical hazard ratio (HR) limit of 1.338. Physician-recorded toxicity was measured according to the Radiation Therapy Oncology Group (RTOG) morbidity scale and patient-reported outcome measurements with the Prostate Cancer Symptom Scale (PCSS) questionnaire. This trial is registered with the ISRCTN registry, number ISRCTN45905321.

Findings: Between July 1, 2005, and Nov 4, 2015, 1200 patients were randomly assigned to conventional fractionation (n=602) or ultra-hypofractionation (n=598), of whom 1180 (591 conventional fractionation and 589 ultra-hypofractionation) constituted the per-protocol population. 1054 (89%) participants were intermediate risk and 126 (11%) were high risk. Median follow-up time was 5.0 years (IQR 3.1-7.0). The estimated failure-free survival at 5 years was 84% (95% CI 80-87) in both treatment groups, with an adjusted HR of 1.002 (95% CI 0.758-1.325; log-rank p=0.99). There was weak evidence of an increased frequency of acute physician-reported RTOG grade 2 or worse urinary toxicity in the ultra-hypofractionation group at end of radiotherapy (158 [28%] of 569 patients vs 132 [23%] of 578 patients; p=0.057). There were no significant differences in grade 2 or worse urinary or bowel late toxicity between the two treatment groups at any point after radiotherapy, except for an increase in urinary toxicity in the ultra-hypofractionation group compared to the conventional fractionation group at 1-year follow-up (32 [6%] of 528 patients vs 13 [2%] of 529 patients; (p=0.0037). We observed no differences between groups in frequencies at 5 years of RTOG grade 2 or worse urinary toxicity (11 [5%] of 243 patients for the ultra-hypofractionation group vs 12 [5%] of 249 for the conventional fractionation group; p=1.00) and bowel toxicity (three [1%] of 244 patients vs nine [4%] of 249 patients; p=0.14). Patient-reported outcomes revealed significantly higher levels of acute urinary and bowel symptoms in the ultra-hypofractionation group compared with the conventional fractionation group but no significant increases in late symptoms were found, except for increased urinary symptoms at 1-year follow-up, consistent with the physician-evaluated toxicity.

Interpretation: Ultra-hypofractionated radiotherapy is non-inferior to conventionally fractionated radiotherapy for intermediate-to-high risk prostate cancer regarding failure-free survival. Early side-effects are more pronounced with ultra-hypofractionation compared with conventional fractionation whereas late toxicity is similar in both treatment groups. The results support the use of ultra-hypofractionation for radiotherapy of prostate cancer. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-75781 (URN)10.1016/S0140-6736(19)31131-6 (DOI)000478698300023 ()31227373 (PubMedID)
Funder
Swedish Cancer SocietySwedish Research Council
Note

Funding Agency:

Nordic Cancer Union

Available from: 2019-08-16 Created: 2019-08-16 Last updated: 2019-08-16Bibliographically approved
Tagliaferri, L., Budrukkar, A., Lenkowicz, J., Cambeiro, M., Bussu, F., Guinot, J. L., . . . Kovacs, G. (2018). ENT COBRA ONTOLOGY: the covariates classification system proposed by the Head & Neck and Skin GEC-ESTRO Working Group for interdisciplinary standardized data collection in head and neck patient cohorts treated with interventional radiotherapy (brachytherapy). Journal of Contemporary Brachytherapy, 10(3), 260-266
Open this publication in new window or tab >>ENT COBRA ONTOLOGY: the covariates classification system proposed by the Head & Neck and Skin GEC-ESTRO Working Group for interdisciplinary standardized data collection in head and neck patient cohorts treated with interventional radiotherapy (brachytherapy)
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2018 (English)In: Journal of Contemporary Brachytherapy, ISSN 1689-832X, E-ISSN 2081-2841, Vol. 10, no 3, p. 260-266Article, review/survey (Refereed) Published
Abstract [en]

Purpose: Clinical data collecting is expensive in terms of time and human resources. Data can be collected in different ways; therefore, performing multicentric research based on previously stored data is often difficult. The primary objective of the ENT COBRA (COnsortium for BRachytherapy data Analysis) ontology is to define a specific terminological system to standardized data collection for head and neck (H&N) cancer patients treated with interventional radiotherapy.

Material and methods: ENT-COBRA is a consortium for standardized data collection for H&N patients treated with interventional radiotherapy. It is linked to H&N and Skin GEC-ESTRO Working Group and includes 11 centers from 6 countries. Its ontology was firstly defined by a multicentric working group, then evaluated by the consortium followed by a multi-professional technical commission involving a mathematician, an engineer, a physician with experience in data storage, a programmer, and a software expert.

Results: Two hundred and forty variables were defined on 13 input forms. There are 3 levels, each offering a specific type of analysis: 1. Registry level (epidemiology analysis); 2. Procedures level (standard oncology analysis); 3. Research level (radiomics analysis). The ontology was approved by the consortium and technical commission; an ad-hoc software architecture ("broker") remaps the data present in already existing storage systems of the various centers according to the shared terminology system. The first data sharing was successfully performed using COBRA software and the ENT COBRA Ontology, automatically collecting data directly from 3 different hospital databases (Lubeck, Navarra, and Rome) in November 2017.

Conclusions: The COBRA Ontology is a good response to the multi-dimensional criticalities of data collection, retrieval, and usability. It allows to create a software for large multicentric databases with implementation of specific remapping functions wherever necessary. This approach is well-received by all involved parties, primarily because it does not change a single center's storing technologies, procedures, and habits.

Place, publisher, year, edition, pages
Termedia Publishing, 2018
Keywords
data collection, ENT-COBRA, head and neck cancer, GEC-ESTRO, personalized medicine
National Category
Cancer and Oncology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:oru:diva-68257 (URN)10.5114/jcb.2018.76982 (DOI)000438333100011 ()30038647 (PubMedID)
Available from: 2018-07-27 Created: 2018-07-27 Last updated: 2018-09-12Bibliographically approved
Widmark, A., Gunnlaugsson, A., Beckman, L., Thellenberg-Karlsson, C., Hoyer, M., Lagerlund, M., . . . Nilsson, P. (2018). Ultrahypofractionation for prostate cancer: Outcome from the Scandinavian phase 3 HYPO-RT-PC trial. Paper presented at 37th Meeting of the European-Society-for-Radiotherapy-and-Oncology (ESTRO), Barcelona, Spain, April 20-24, 2018. Radiotherapy and Oncology, 127(Suppl. 1), S314-S314
Open this publication in new window or tab >>Ultrahypofractionation for prostate cancer: Outcome from the Scandinavian phase 3 HYPO-RT-PC trial
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2018 (English)In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 127, no Suppl. 1, p. S314-S314Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Elsevier, 2018
National Category
Cancer and Oncology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:oru:diva-68480 (URN)10.1016/S0167-8140(18)30909-5 (DOI)000437723401204 ()
Conference
37th Meeting of the European-Society-for-Radiotherapy-and-Oncology (ESTRO), Barcelona, Spain, April 20-24, 2018
Available from: 2018-08-15 Created: 2018-08-15 Last updated: 2018-09-05Bibliographically approved
Hjortshøj, C. S., Jensen, A. S., Sørensen, K., Nagy, E., Johansson, B., Kronvall, T., . . . Søndergaard, L. (2017). Epidemiological changes in Eisenmenger syndrome in the Nordic region in 1977-2012. Heart, 103(17), 1353-1358
Open this publication in new window or tab >>Epidemiological changes in Eisenmenger syndrome in the Nordic region in 1977-2012
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2017 (English)In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 17, p. 1353-1358Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Improved diagnostic tools, timely closure of the shunt and a better understanding of the complexity of Eisenmenger syndrome (ES) have led to improved care and treatment in tertiary centres. These may have decreased the incidence of ES and improved survival of patients with ES, although evidence is still lacking. The aim of this study was to investigate temporal changes in incidence, prevalence and mortality in patients with ES for 35 years in the Nordic region.

METHODS: This was a retrospective population-based study including 714 patients with ES. Survival analysis was performed based on all-cause mortality and accounting for immortal time bias.

RESULTS: The incidence of ES decreased from 2.5/million inhabitants/year in 1977 to 0.2/million inhabitants/year in 2012. Correspondingly, prevalence decreased from 24.6 to 11.9/million inhabitants. The median survival was 38.4 years, with 20-year, 40-year and 60-year survival of 72.5%, 48.4%, and 21.3%, respectively. Complex lesions and Down syndrome were independently associated with worse survival (HR 2.2, p<0.001 and HR 1.8, p<0.001, respectively). Age at death increased from 27.7 years in the period from 1977 to 1992, to 46.3 years from July 2006 to 2012 (p<0.001).

CONCLUSIONS: The incidence and prevalence of ES in the Nordic region have decreased markedly during the last decades. Furthermore, the median age at death increased throughout the study period, indicating prolonged life expectancy in the ES population. However, increasing age represents decreased incidence, rather than improved survival. Nonetheless, longevity with ES is still shorter than in the background population.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2017
Keywords
Eisenmenger syndrome, adult congenital heart disease, epidemiology, pulmonary arterial hypertension, survival
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:oru:diva-60907 (URN)10.1136/heartjnl-2016-310979 (DOI)000407613900010 ()28450553 (PubMedID)2-s2.0-85027546882 (Scopus ID)
Note

Funding agencies:

Actelion Denmark (a branch of Actelion Pharmaceuticals in Sweden)

Available from: 2017-09-19 Created: 2017-09-19 Last updated: 2017-10-22Bibliographically approved
Kovács, G., Martinez-Monge, R., Budrukkar, A., Guinot, J. L., Johansson, B., Strnad, V., . . . Siebert, F.-A. (2017). GEC-ESTRO ACROP recommendations for head & neck brachytherapy in squamous cell carcinomas: 1st update - Improvement by cross sectional imaging based treatment planning and stepping source technology. Radiotherapy and Oncology, 122(2), 248-254
Open this publication in new window or tab >>GEC-ESTRO ACROP recommendations for head & neck brachytherapy in squamous cell carcinomas: 1st update - Improvement by cross sectional imaging based treatment planning and stepping source technology
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2017 (English)In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 122, no 2, p. 248-254Article in journal (Refereed) Published
Abstract [en]

The Head and Neck Working Group of the GEC-ESTRO (Groupe Européen de Curiethérapie - European Society for Therapeutic Radiology and Oncology) published in 2009 the consensus recommendations for low-dose rate, pulsed-dose rate and high-dose rate brachytherapy in head & neck cancers. The use of brachytherapy in combination with external beam radiotherapy and/or surgery was also covered as well as the use of brachytherapy in previously irradiated patients. Given the developments in the field, these recommendations needed to be updated to reflect up-to-date knowledge.

The present update does not repeat basic knowledge which was published in the first recommendation but covers in a general part developments in (1) dose and fractionation, (2) aspects of treatment selection for brachytherapy alone versus combined BT+EBRT and (3) quality assurance issues.

Detailed expert committee opinion intends to help the clinical practice in lip-, oral cavity-, oropharynx-, nasopharynx-, and superficial cancers. Different aspects of adjuvant treatment techniques and their results are discussed, as well the possibilities of salvage brachytherapy applications.

Place, publisher, year, edition, pages
Clare, Ireland: Elsevier, 2017
Keywords
Head & neck, brachytherapy, recommendation, GEC-ESTRO
National Category
Radiology, Nuclear Medicine and Medical Imaging Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-53661 (URN)10.1016/j.radonc.2016.10.008 (DOI)000395607300013 ()27889184 (PubMedID)2-s2.0-85007246630 (Scopus ID)
Available from: 2016-11-28 Created: 2016-11-28 Last updated: 2018-08-31Bibliographically approved
Wikström, J., Isacsson, U., Johansson, B. & Lennernäs, B. (2017). Magnetic Resonance Compatibility of a Transponder Aimed for Radiotherapy Positioning - A Phantom Study. Anticancer Research, 37(9), 4993-4996
Open this publication in new window or tab >>Magnetic Resonance Compatibility of a Transponder Aimed for Radiotherapy Positioning - A Phantom Study
2017 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 37, no 9, p. 4993-4996Article in journal (Refereed) Published
Abstract [en]

Background/Aim: Electromagnetic Positioning Systems (EMP) is a new position-ing technique in four-dimensional radiotherapy. Patients with implanted transponders may be referred for magnetic resonance imaging (MRI) making it important to establish the MR safety.

Materials and Methods: Oranges were prepared with transponders and imaged on a 3T MR scanner with different sequences. Computed tomography (CT) was performed as comparison. MR artifacts were assessed. An estimation of the maximum transponder de-flection force and heating was made.

Results: The mean measured displacement of transponders was 0.1 mm (range=0.03-0.3 mm). Artifacts were observed adjacent to transponders using all sequences. The deflection force on the transponder in the gantry was less than 38 mN. No heating was observed.

Conclusion: The absence of any substantial movement, the weak measured deflection force and absence of observed heating speaks for the safe use of MR imaging with transponder 3T. Local artefacts makes evaluation impossible adjacent to transponders.

Place, publisher, year, edition, pages
International Institute of Anticancer Research, 2017
Keywords
Prostate cancer, electromagnetic positioning, four dimensional radiotherapy
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-61934 (URN)10.21873/anticanres.11911 (DOI)000412578200034 ()28870923 (PubMedID)2-s2.0-85029427695 (Scopus ID)
Available from: 2017-10-24 Created: 2017-10-24 Last updated: 2018-08-07Bibliographically approved
Nyholm, T., Olsson, C., Agrup, M., Björk, P., Björk-Eriksson, T., Gagliardi, G., . . . Montelius, A. (2016). A national approach for automated collection of standardized and population-based radiation therapy data in Sweden. Radiotherapy and Oncology, 119(2), 344-350
Open this publication in new window or tab >>A national approach for automated collection of standardized and population-based radiation therapy data in Sweden
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2016 (English)In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 119, no 2, p. 344-350Article in journal (Refereed) Published
Abstract [en]

Purpose: To develop an infrastructure for structured and automated collection of interoperable radiation therapy (RT) data into a national clinical quality registry.

Materials and methods: The present study was initiated in 2012 with the participation of seven of the 15 hospital departments delivering RT in Sweden. A national RT nomenclature and a database for structured unified storage of RT data at each site (Medical Information Quality Archive, MIQA) have been developed. Aggregated data from the MIQA databases are sent to a national RT registry located on the same IT platform (INCA) as the national clinical cancer registries.

Results: The suggested naming convention has to date been integrated into the clinical workflow at 12 of 15 sites, and MIQA is installed at six of these. Involvement of the remaining 3/15 RT departments is ongoing, and they are expected to be part of the infrastructure by 2016. RT data collection from ARIA (R), Mosaiq (R), Eclipse (TM), and Oncentra (R) is supported. Manual curation of RT-structure information is needed for approximately 10% of target volumes, but rarely for normal tissue structures, demonstrating a good compliance to the RT nomenclature. Aggregated dose/volume descriptors are calculated based on the information in MIQA and sent to INCA using a dedicated service (MIQA2INCA). Correct linkage of data for each patient to the clinical cancer registries on the INCA platform is assured by the unique Swedish personal identity number.

Conclusions: An infrastructure for structured and automated prospective collection of syntactically inter operable RT data into a national clinical quality registry for RT data is under implementation. Future developments include adapting MIQA to other treatment modalities (e.g. proton therapy and brachytherapy) and finding strategies to harmonize structure delineations. How the RT registry should comply with domain-specific ontologies such as the Radiation Oncology Ontology (ROO) is under discussion. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
Radiation therapy data, Radiation Oncology informatics, Medical informatics, Data standardization, Data integration
National Category
Cancer and Oncology Radiology, Nuclear Medicine and Medical Imaging
Research subject
Oncology; Radiology
Identifiers
urn:nbn:se:oru:diva-51579 (URN)10.1016/j.radonc.2016.04.007 (DOI)000379559400023 ()27102842 (PubMedID)2-s2.0-84973639276 (Scopus ID)
Funder
VINNOVA
Note

Funding Agencies:

Swedish Radiation Safety Authority

Cancer Research Foundation in Northern Sweden

U-CAN, the Swedish testbed for innovative radiotherapy

Regional Cancer Centres and Gentle Radiotherapy

Available from: 2016-08-04 Created: 2016-08-04 Last updated: 2018-09-07Bibliographically approved
Tagliaferri, L., Kovacs, G., Autorino, R., Budrukkar, A., Luis Guinot, J., Hildebrand, G., . . . Valentini, V. (2016). ENT COBRA (Consortium for Brachytherapy Data Analysis): interdisciplinary standardized data collection system for head and neck patients treated with interventional radiotherapy (brachytherapy). Journal of Contemporary Brachytherapy, 8(4), 336-343
Open this publication in new window or tab >>ENT COBRA (Consortium for Brachytherapy Data Analysis): interdisciplinary standardized data collection system for head and neck patients treated with interventional radiotherapy (brachytherapy)
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2016 (English)In: Journal of Contemporary Brachytherapy, ISSN 1689-832X, E-ISSN 2081-2841, Vol. 8, no 4, p. 336-343Article, review/survey (Refereed) Published
Abstract [en]

Purpose: Aim of the COBRA (Consortium for Brachytherapy Data Analysis) project is to create a multicenter group (consortium) and a web-based system for standardized data collection.

Material and methods: GEC-ESTRO (Groupe Europeen de Curietherapie - European Society for Radiotherapy & Oncology) Head and Neck (H&N) Working Group participated in the project and in the implementation of the consortium agreement, the ontology (data-set) and the necessary COBRA software services as well as the peer reviewing of the general anatomic site-specific COBRA protocol. The ontology was defined by a multicenter task-group.

Results: Eleven centers from 6 countries signed an agreement and the consortium approved the ontology. We identified 3 tiers for the data set: Registry (epidemiology analysis), Procedures (prediction models and DSS), and Research (radiomics). The COBRA-Storage System (C-SS) is not time-consuming as, thanks to the use of "brokers", data can be extracted directly from the single center's storage systems through a connection with "structured query language database" (SQL-DB), Microsoft Access, FileMaker Pro, or Microsoft Excel. The system is also structured to perform automatic archiving directly from the treatment planning system or afterloading machine. The architecture is based on the concept of "on-purpose data projection". The C-SS architecture is privacy protecting because it will never make visible data that could identify an individual patient. This C-SS can also benefit from the so called "distributed learning" approaches, in which data never leave the collecting institution, while learning algorithms and proposed predictive models are commonly shared.

Conclusions: Setting up a consortium is a feasible and practicable tool in the creation of an international and multi-system data sharing system. COBRA C-SS seems to be well accepted by all involved parties, primarily because it does not influence the center's own data storing technologies, procedures, and habits. Furthermore, the method preserves the privacy of all patients.

Place, publisher, year, edition, pages
Termedia Publishing House Ltd., 2016
Keywords
consortium, data collection, ENT-COBRA, head and neck cancer
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-52696 (URN)10.5114/jcb.2016.61958 (DOI)000382808100008 ()27648088 (PubMedID)2-s2.0-84983611820 (Scopus ID)
Available from: 2016-10-03 Created: 2016-09-30 Last updated: 2018-07-17Bibliographically approved
Karlsson, L., Thunberg, P., Johansson, B. & Persliden, J. (2014). The impact of activating source dwell positions outside the CTV on the dose to treated normal tissue volumes in TRUS guided 3D conformal interstitial HDR brachytherapy of prostate cancer. Journal of Contemporary Brachytherapy, 6(3), 282-288
Open this publication in new window or tab >>The impact of activating source dwell positions outside the CTV on the dose to treated normal tissue volumes in TRUS guided 3D conformal interstitial HDR brachytherapy of prostate cancer
2014 (English)In: Journal of Contemporary Brachytherapy, ISSN 1689-832X, E-ISSN 2081-2841, Vol. 6, no 3, p. 282-288Article in journal (Refereed) Published
Abstract [en]

Purpose: Dose coverage is crucial for successful treatment in mono-brachytherapy. Since few and very high dose fractions are used, there is an important balance between dwell positioning outside the clinical target volume (CTV) and possible damage on adjacent normal tissue. The purpose of this study was to evaluate the possibility of having dwell positions close to the CTV surface, while maintaining an acceptable dose distribution, and to investigate the robustness in terms of known geometrical uncertainties of the implant.

Material and methods: This study included 37 patients who had received brachytherapy for prostate cancer as a monotherapy with the following schedules: 2 x 14 Gy or 3 x 11 Gy, each fraction separated by two weeks. The source dwell positions were activated 5 mm outside CTV. New optimizations were simulated for dwell positions at 3, 2, 1, and 0 mm. Inverse and graphical optimization were applied according to the relative dose constraints: V-100 CTV >= 97%, D-max,D- urethra <= 110%, and D-10 rectal mucosa <= 65%. The V-100 normal tissue outside CTV was used to evaluate dose variations caused by different dwell positions. Prostate geometries and dose distributions for the different dwell positions outside the CTV were used to investigate the impact on the CTV dose distribution due to geometrical uncertainties.

Results: Both V-100,V- CTV, and V-100,V- normal tissue decreased, 98.6% to 92.2%, and 17 cm(3) to 9.0 cm(3), for dwell activation from 5 rum to 0 mm. The evaluation of both simulated longitudinal geometrical uncertainties and different source dwell activations implied that V-100,V- CTV ranged from 98.6% to 86.3%.

Conclusions: It is possible to reduce the V-100,V- normal tissue by decreasing the source dwell positions outside the CTV from 5 to 3 mm, while maintaining dose constraints. In combination with the estimated geometrical uncertainties, however, the source dwell positions need to be 5 mm from the surface in order to maintain a robust implant.

Place, publisher, year, edition, pages
Termedia Publishing House, 2014
Keywords
brachytherapy, margins, optimization, prostate cancer
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-39464 (URN)10.5114/jcb.2014.45586 (DOI)000344200000006 ()25337130 (PubMedID)2-s2.0-84907706206 (Scopus ID)
Available from: 2014-12-10 Created: 2014-12-10 Last updated: 2018-06-14Bibliographically approved
Johansson, B. (2010). Long-term outcome research on PDR brachytherapy with focus on breast, base of tongue and lip cancer. (Doctoral dissertation). Örebro: Örebro universitet
Open this publication in new window or tab >>Long-term outcome research on PDR brachytherapy with focus on breast, base of tongue and lip cancer
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Brachytherapy (BT) with continuous low dose rate (LDR) has been used for 100 years and is considered as the radiotherapy method able to deliver a dose in the shortest time with high efficacy and low risk of side effects. The drawbacks are need for patient isolation and radiation exposure of the staff during the treatment.

Brenner and Hall published the radiobiology concept for pulsed dose rate (PDR) in 1991.  Short (10-20 minutes), hourly pulses of high dose rate (HDR) given to the same dose, with same overall treatment time will virtually simulate continuous LDR. At the same time new afterloading machine technology became available, where a single millimetre sized radiation 192Iridium source sequentially moves through the applicator in small individually timed steps. The advantages are that the radiation dose can be optimized along the applicator and with no radiation exposure of the staff and no need for patient isolation more than during the pulse. This work deals with four different aspects of PDR BT

An experimental comparison of measured absorbed doses outside a left sided breast target on a body equivalent Alderson phantom was made.  Five external beam radiotherapy (EBRT) whole breast treatments to 50 Gy versus five accelerated partial breast irradiations (APBI) by PDR BT to 50 Gy were studied. The absorbed doses were measured in 67 different positions inside the body phantom by thermoluminescence dosimeters. The result shows that dose points distant to the left breast will have 1-1.4 % of the prescribed dose with no difference between EBRT and PDR BT. Organs at risk in short distance (<5 cm) to the target (such as parts of the left lung, heart muscle and the right breast) will have significantly less dose by PDR BT. In conclusion PDR BT has dosimetric advantages close to the target compared to EBRT and cannot do more damage to remote organs.

PDR APBI as the adjuvant RT treatment to breast conserving surgery after early breast cancer was studied. Between 1994-2004 we treated 50 women and 51 breasts. The median age of the population was 53 (40-72) years. The cases were radically resected, unifocal T1-2N0-1M0 tumours. PDR BT was given to a dose of 50 Gy for 5 days directed to the operated sector of the breast. The median treated volume was 160 cm3, constituting in median 31 % of the breast volume. The treatment is called accelerated because total treatment time is 5 days compared to 5 weeks for EBRT. After a median follow-up of 130 months (>10 years) we noted 5 (10 %) local recurrences in the treated breast. Four of these recurrences were outside the treated volume. Three women (6 %) developed cancers in the other breast. Early side effects were mild and less than with EBRT. As late side effects we found mild to moderate local fibroses in the treated volume. A cosmetic evaluation was done by both the patient and a nurse and was found to be lower than in other published data (56 % = good to excellent). The 10 years local failure rate is similar to the result from a large Swedish randomized study on whole breast radiotherapy to 50 Gy. The study indicates that PDR BT is highly effective.

A combination of EBRT (40.8 Gy) and PDR boost (35 Gy) to T1-4N0-3M0, base of tongue (BOT) cancer, treated during 1994-2007 was analyzed. The study is the first with PDR and second largest with BT worldwide. A number of 83 patients with a median age of 60 (38-82) years were included. BT was given to a mean volume of 58 ccm 2 days after the neck dissection. Median follow-up was 54 months. At 5 years we found 89 % local tumour control, 95 % neck control, 80 % disease free survival and an overall survival of 65 %. Late side effects were 13 % minor transient soft tissue necrosis and 12 % long lasting or permanent soft tissue- or osteoradio-necrosis. The results are among the best published worldwide. An extensive quality of life analysis was done on 45 patients at last follow-up and showed limited, persistent xerostomia and dysphagia. The global quality of life was rated good in 75 % of the patients.

The last study presented was PDR mono-brachytherapy (55-60 Gy) to cancer of the lip (T1-3N0M0). The study included 43 patients with a median age of 74 (37-92) years. The treatment time was 5.5-6 days and the mean treated volume was 15 ccm. The median follow-up time was 54 (1-158) months. Five year Kaplan-Meier data showed, local control 94 %, disease free survival 86 % and overall survival 59 %. An early side effect was a strong radiation mucositis and dermatitis, which healed in 1 month. Late side effects were uncommon and the cosmetic appearance and the lip function were found to be normal. Our data in total and per T-stage was compared to a European survey from 1993 on 2794 patients treated by LDR BT. The results are similar and are a strong indication of equal efficacy between PDR and LDR.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2010. p. 81
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 42
Keywords
PDR, brachytherapy, outcome, partial breast irradiation, base of tongue cancer, lip cancer, quality of life, dosimetry.
National Category
Cancer and Oncology Surgery
Research subject
Oncology; Surgery
Identifiers
urn:nbn:se:oru:diva-10423 (URN)978-91-7668-723-9 (ISBN)
Public defence
2010-05-21, Wilandersalen, M-huset, bottenvåning, Universitetssjukhuset, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2010-04-20 Created: 2010-04-20 Last updated: 2017-10-18Bibliographically approved
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