umu.sePublications
Change search
Link to record
Permanent link

Direct link
BETA
Thellenberg-Karlsson, Camilla
Alternative names
Publications (10 of 33) Show all publications
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
Show others...
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-RT-PC 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.

Funding: The Nordic Cancer Union, the Swedish Cancer Society, and the Swedish Research Council.

Place, publisher, year, edition, pages
Elsevier, 2019
National Category
Nursing
Identifiers
urn:nbn:se:umu:diva-162730 (URN)10.1016/S0140-6736(19)31131-6 (DOI)000478698300023 ()31227373 (PubMedID)2-s2.0-85069673767 (Scopus ID)
Available from: 2019-08-27 Created: 2019-08-27 Last updated: 2019-08-30Bibliographically approved
Gronlund, E., Johansson, S., Nyholm, T., Thellenberg, C. & Ahnesjo, A. (2018). Dose painting of prostate cancer based on Gleason score correlations with apparent diffusion coefficients. Acta Oncologica, 57(5), 574-581
Open this publication in new window or tab >>Dose painting of prostate cancer based on Gleason score correlations with apparent diffusion coefficients
Show others...
2018 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 5, p. 574-581Article in journal (Refereed) Published
Abstract [en]

Background: Gleason scores for prostate cancer correlates with an increased recurrence risk after radiotherapy (RT). Furthermore, higher Gleason scores correlates with decreasing apparent diffusion coefficient (ADC) data from diffusion weighted MRI (DWI-MRI). Based on these observations, we present a formalism for dose painting prescriptions of prostate volumes based on ADC images mapped to Gleason score driven dose-responses.

Methods: The Gleason score driven dose-responses were derived from a learning data set consisting of pre-RT biopsy data and post-RT outcomes for 122 patients treated with a homogeneous dose to the prostate. For a test data set of 18 prostate cancer patients with pre-RT ADC images, we mapped the ADC data to the Gleason driven dose-responses by using probability distributions constructed from published Gleason score correlations with ADC data. We used the Gleason driven dose-responses to optimize dose painting prescriptions that maximize the tumor control probability (TCP) with equal average dose as for the learning sets homogeneous treatment dose.

Results: The dose painting prescriptions increased the estimated TCP compared to the homogeneous dose by 0–51% for the learning set and by 4–30% for the test set. The potential for individual TCP gains with dose painting correlated with increasing Gleason score spread and larger prostate volumes. The TCP gains were also found to be larger for patients with a low expected TCP for the homogeneous dose prescription.

Conclusions: We have from retrospective treatment data demonstrated a formalism that yield ADC driven dose painting prescriptions for prostate volumes that potentially can yield significant TCP increases without increasing dose burdens as compared to a homogeneous treatment dose. This motivates further development of the approach to consider more accurate ADC to Gleason mappings, issues with delivery robustness of heterogeneous dose distributions, and patient selection criteria for design of clinical trials.

National Category
Urology and Nephrology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-147489 (URN)10.1080/0284186X.2017.1415457 (DOI)000430114000002 ()29260950 (PubMedID)
Funder
Swedish Cancer Society, 130632
Available from: 2018-05-04 Created: 2018-05-04 Last updated: 2018-06-09Bibliographically approved
Björeland, U., Jonsson, J., Alm, M., Beckman, L., Nyholm, T. & Thellenberg-Karlsson, C. (2018). Inter-fraction movements of the prostate and pelvic lymph nodes during IGRT. Journal of radiation oncology, 7(4), 357-366
Open this publication in new window or tab >>Inter-fraction movements of the prostate and pelvic lymph nodes during IGRT
Show others...
2018 (English)In: Journal of radiation oncology, ISSN 1948-7894, Vol. 7, no 4, p. 357-366Article in journal (Refereed) Published
Abstract [en]

Objectivities: The aim of this study was to evaluate inter-fraction movements of lymph node regions that are commonly included in the pelvic clinical target volume (CTV) for high-risk prostate cancer patients. We also aimed to evaluate if the movements affect the planning target volumes. Methods: Ten prostate cancer patients were included. The patients underwent six MRI scans, from treatment planning to near end of treatment. The CTV movements were analyzed with deformable registration technique with the CTV divided into sections. The validity of the deformable registration was assessed by comparing the results for individual lymph nodes that were possible to identify in all scans. Results: Using repetitive MRI, measurements showed that areas inside the CTV (lymph nodes) in some extreme cases were as mobile as the prostate and not fixed to the bones. The lymph node volumes closest to the prostate did not tend to follow the prostate motion. The more cranial lymph node volumes moved less, but still independently, and they were not necessarily fixed to the pelvic bones. In 95% of the cases, the lymph node motion in the R-L direction was 2-4mm, in the A-P direction 2-7mm, and in the C-C direction 2-5mm depending on the CTV section. Conclusion: Lymph nodes and prostate were most mobile in the A-P direction, followed by the C-C and R-L directions. This movement should be taken into account when deciding the margins for the planning target volumes (PTV).

Place, publisher, year, edition, pages
Springer, 2018
Keywords
Prostate, Lymph nodes, CTV, Movements
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-154896 (URN)10.1007/s13566-018-0366-3 (DOI)000452890500007 ()30595810 (PubMedID)
Available from: 2019-01-07 Created: 2019-01-07 Last updated: 2019-01-07Bibliographically approved
Tjon-Kon-Fat, L.-A., Lundholm, M., Schröder, M., Wurdinger, T., Thellenberg-Karlsson, C., Widmark, A., . . . Nilsson, R. J. (2018). Platelets harbor prostate cancer biomarkers and the ability to predict therapeutic response to abiraterone in castration resistant patients. The Prostate, 78(1), 48-53
Open this publication in new window or tab >>Platelets harbor prostate cancer biomarkers and the ability to predict therapeutic response to abiraterone in castration resistant patients
Show others...
2018 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 78, no 1, p. 48-53Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Novel therapies for castration resistant prostate cancer (CRPC) have been introduced in the clinic with possibilities for individualized treatment plans. Best practice of those expensive drugs requires predictive biomarker monitoring. This study used circulating biomarker analysis to follow cancer-derived transcripts implicated in therapy resistance.

METHOD: The isolated platelet population of blood samples and digital-PCR were used to identify selected biomarker transcripts in patients with CRPC prior chemo- or androgen synthesis inhibiting therapy.

RESULTS: Fifty patients received either docetaxel (n = 24) or abiraterone (n = 26) therapy, with therapy response rates of 54% and 48%, respectively. Transcripts for the PC-associated biomarkers kallikrein-related peptidase-2 and -3 (KLK2, KLK3), folate hydrolase 1 (FOLH1), and neuropeptide-Y (NPY) were uniquely present within the platelet fraction of cancer patients and not detected in healthy controls (n = 15). In the abiraterone treated cohort, the biomarkers provided information on therapy outcome, demonstrating an association between detectable biomarkers and short progression free survival (PFS) (FOLH1, P < 0.01; KLK3, P < 0.05; and NPY, P < 0.05). Patients with biomarker-negative platelets had the best outcome, while FOLH1 (P < 0.05) and NPY (P = 0.05) biomarkers provided independent predictive information in a multivariate analysis regarding PFS. KLK2 (P < 0.01), KLK3 (P < 0.001), and FOLH1 (P < 0.05) biomarkers were associated with short overall survival (OS). Combining three biomarkers in a panel (KLK3, FOLH1, and NPY) made it possible to separate long-term responders from short-term responders with 87% sensitivity and 82% specificity.

CONCLUSION: Analyzing tumor-derived biomarkers in platelets of CRPC patients enabled prediction of the outcome after abiraterone therapy with higher accuracy than baseline serum PSA or PSA response.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2018
Keywords
biomarkers, liquid biopsy, personalized medicine, platelet, prostate cancer, therapy stratification
National Category
Cancer and Oncology Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-142384 (URN)10.1002/pros.23443 (DOI)000417131400007 ()29094381 (PubMedID)
Available from: 2017-11-29 Created: 2017-11-29 Last updated: 2018-06-09Bibliographically approved
Adjeiwaah, M., Bylund, M., Lundman, J. A., Thellenberg Karlsson, C., Jonsson, J. H. & Nyholm, T. (2018). Quantifying the effect of 3T MRI residual system and patient-induced susceptibility distortions on radiotherapy treatment planning for prostate cancer. International Journal of Radiation Oncology, Biology, Physics, 100(2), 317-324
Open this publication in new window or tab >>Quantifying the effect of 3T MRI residual system and patient-induced susceptibility distortions on radiotherapy treatment planning for prostate cancer
Show others...
2018 (English)In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 100, no 2, p. 317-324Article in journal (Refereed) Published
Abstract [en]

Purpose: To investigate the effect of magnetic resonance system- and patient-induced susceptibility distortions from a 3T scanner on dose distributions for prostate cancers.

Methods and Materials: Combined displacement fields from the residual system and patient-induced susceptibility distortions were used to distort 17 prostate patient CT images. VMAT dose plans were initially optimized on distorted CT images and the plan parameters transferred to the original patient CT images to calculate a new dose distribution.

Results: Maximum residual mean distortions of 3.19 mm at a radial distance of 25 cm and maximum mean patient-induced susceptibility shifts of 5.8 mm were found using the lowest bandwidth of 122 Hz per pixel. There was a dose difference of <0.5% between distorted and undistorted treatment plans. The 90% confidence intervals of the mean difference between the dCT and CT treatment plans were all within an equivalence interval of (−0.5, 0.5) for all investigated plan quality measures.

Conclusions: Patient-induced susceptibility distortions at high field strengths in closed bore magnetic resonance scanners are larger than residual system distortions after using vendor-supplied 3-dimensional correction for the delineated regions studied. However, errors in dose due to disturbed patient outline and shifts caused by patient-induced susceptibility effects are below 0.5%.

Place, publisher, year, edition, pages
Elsevier, 2018
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-142319 (URN)10.1016/j.ijrobp.2017.10.021 (DOI)000423097500011 ()29229326 (PubMedID)
Available from: 2017-11-27 Created: 2017-11-27 Last updated: 2018-06-09Bibliographically approved
Glimelius, B., Melin, B., Enblad, G., Alafuzoff, I., Beskow, A., Ahlström, H., . . . Sjöblom, T. (2018). U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden. Acta Oncologica, 57(2), 187-194
Open this publication in new window or tab >>U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden
Show others...
2018 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 2, p. 187-194Article in journal (Refereed) Published
Abstract [en]

Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umea Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.

Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.

Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.

Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-144850 (URN)10.1080/0284186X.2017.1337926 (DOI)000423473200003 ()28631533 (PubMedID)
Available from: 2018-02-23 Created: 2018-02-23 Last updated: 2018-06-09Bibliographically 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), APR 20-24, 2018, Barcelona, SPAIN. Radiotherapy and Oncology, 127, S314-S314
Open this publication in new window or tab >>Ultrahypofractionation for prostate cancer: Outcome from the Scandinavian phase 3 HYPO-RT-PC trial
Show others...
2018 (English)In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 127, p. S314-S314Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Elsevier, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-150492 (URN)10.1016/S0167-8140(18)30909-5 (DOI)000437723401204 ()
Conference
37th Meeting of the European-Society-for-Radiotherapy-and-Oncology (ESTRO), APR 20-24, 2018, Barcelona, SPAIN
Available from: 2018-11-01 Created: 2018-11-01 Last updated: 2018-11-01Bibliographically approved
Wirth, M., Saad, F., Keizman, D., O'Sullivan, J. M., Carles, J., Gillessen, S., . . . Heinrich, D. (2017). Analysis of overall survival by number of radium-223 injections received in an international expanded access program (iEAP). Oncology Research and Treatment, 40, 320-320
Open this publication in new window or tab >>Analysis of overall survival by number of radium-223 injections received in an international expanded access program (iEAP)
Show others...
2017 (English)In: Oncology Research and Treatment, ISSN 2296-5270, Vol. 40, p. 320-320Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
S. Karger, 2017
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-137929 (URN)000405108300799 ()
Note

Supplement: 3, Meeting Abstract: V1031

Available from: 2017-08-04 Created: 2017-08-04 Last updated: 2018-06-09Bibliographically approved
Andren, O., Widmark, A., Falt, A., Ulvskog, E., Davidsson, S., Thellenberg Karlsson, C. & Hjalm-Eriksson, M. (2017). Cabazitaxel followed by androgen deprivation therapy (ADT) significantly improves time to progression in patients with newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC): A randomized, open label, phase III, multicenter trial. Paper presented at 42nd European-Society-for-Medical-Oncology Congress (ESMO), SEP 08-12, 2017, Madrid, SPAIN. Annals of Oncology, 28
Open this publication in new window or tab >>Cabazitaxel followed by androgen deprivation therapy (ADT) significantly improves time to progression in patients with newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC): A randomized, open label, phase III, multicenter trial
Show others...
2017 (English)In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 28Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2017
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-140910 (URN)000411324002002 ()
Conference
42nd European-Society-for-Medical-Oncology Congress (ESMO), SEP 08-12, 2017, Madrid, SPAIN
Note

Supplement:5, Meeting Abstract: 811P

Available from: 2017-11-20 Created: 2017-11-20 Last updated: 2018-06-09
Brynolfsson, P., Nilsson, D., Torheim, T., Asklund, T., Thellenberg Karlsson, C., Trygg, J., . . . Garpebring, A. (2017). Haralick texture features from apparent diffusion coefficient (ADC) MRI images depend on imaging and pre-processing parameters. Scientific Reports, 7, Article ID 4041.
Open this publication in new window or tab >>Haralick texture features from apparent diffusion coefficient (ADC) MRI images depend on imaging and pre-processing parameters
Show others...
2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 4041Article in journal (Refereed) Published
Abstract [en]

In recent years, texture analysis of medical images has become increasingly popular in studies investigating diagnosis, classification and treatment response assessment of cancerous disease. Despite numerous applications in oncology and medical imaging in general, there is no consensus regarding texture analysis workflow, or reporting of parameter settings crucial for replication of results. The aim of this study was to assess how sensitive Haralick texture features of apparent diffusion coefficient (ADC) MR images are to changes in five parameters related to image acquisition and pre-processing: noise, resolution, how the ADC map is constructed, the choice of quantization method, and the number of gray levels in the quantized image. We found that noise, resolution, choice of quantization method and the number of gray levels in the quantized images had a significant influence on most texture features, and that the effect size varied between different features. Different methods for constructing the ADC maps did not have an impact on any texture feature. Based on our results, we recommend using images with similar resolutions and noise levels, using one quantization method, and the same number of gray levels in all quantized images, to make meaningful comparisons of texture feature results between different subjects.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-134993 (URN)10.1038/s41598-017-04151-4 (DOI)000403874900024 ()28642480 (PubMedID)
Note

Originally included in thesis in manuscript form.

Available from: 2017-05-15 Created: 2017-05-15 Last updated: 2018-06-09Bibliographically approved
Organisations

Search in DiVA

Show all publications