Publications by authors named "Tine Schytte"

38 Publications

ESTRO-ACROP recommendations on the clinical implementation of hybrid MR-linac systems in radiation oncology.

Radiother Oncol 2021 Mar 25. Epub 2021 Mar 25.

Department of Radiation Oncology, University Hospital, LMU Munich, Germany.

Online magnetic resonance-guided radiotherapy (oMRgRT) represents one of the most innovative applications of current image-guided radiation therapy (IGRT). The revolutionary concept of oMRgRT systems is the ability to acquire MR images for adaptive treatment planning and also online imaging during treatment delivery. The daily adaptive planning strategies allow to improve targeting accuracy while avoiding critical structures. This ESTRO-ACROP recommendation aims to provide an overview of available systems and guidance for best practice in the implementation phase of hybrid MR-linac systems. Unlike the implementation of other radiotherapy techniques, oMRgRT adds the MR environment to the daily practice of radiotherapy, which might be a new experience for many centers. New issues and challenges that need to be thoroughly explored before starting clinical treatments will be highlighted.
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http://dx.doi.org/10.1016/j.radonc.2021.03.025DOI Listing
March 2021

High-dose versus standard-dose twice-daily thoracic radiotherapy for patients with limited stage small-cell lung cancer: an open-label, randomised, phase 2 trial.

Lancet Oncol 2021 03;22(3):321-331

Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway; Department of Oncology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

Background: Concurrent chemoradiotherapy is standard treatment for limited stage small-cell lung cancer (SCLC). Twice-daily thoracic radiotherapy of 45 Gy in 30 fractions is considered to be the most effective schedule. The aim of this study was to investigate whether high-dose, twice-daily thoracic radiotherapy of 60 Gy in 40 fractions improves survival.

Methods: This open-label, randomised, phase 2 trial was done at 22 public hospitals in Norway, Denmark, and Sweden. Patients aged 18 years and older with treatment-naive confirmed limited stage SCLC, Eastern Cooperative Oncology Group (ECOG) performance status 0-2, and measurable disease according to the Response Evaluation Criteria in Solid Tumors version 1.1 were eligible. All participants received four courses of intravenous cisplatin 75 mg/m or carboplatin (area under the curve 5-6 mg/mL × min, Calvert's formula) on day 1 and intravenous etoposide 100 mg/m on days 1-3 every 3 weeks. Participants were randomly assigned (1:1) in permuted blocks (sized between 4 and 10) stratifying for ECOG performance status, disease stage, and presence of pleural effusion to receive thoracic radiotherapy of 45 Gy in 30 fractions or 60 Gy in 40 fractions to the primary lung tumour and PET-CT positive lymph node metastases starting 20-28 days after the first chemotherapy course. Patients in both groups received two fractions per day, ten fractions per week. Responders were offered prophylactic cranial irradiation of 25-30 Gy. The primary endpoint, 2-year overall survival, was assessed after all patients had been followed up for a minimum of 2 years. All randomly assigned patients were included in the efficacy analyses, patients commencing thoracic radiotherapy were included in the safety analyses. Follow-up is ongoing. This trial is registered at ClinicalTrials.gov, NCT02041845.

Findings: Between July 8, 2014, and June 6, 2018, 176 patients were enrolled, 170 of whom were randomly assigned to 60 Gy (n=89) or 45 Gy (n=81). Median follow-up for the primary analysis was 49 months (IQR 38-56). At 2 years, 66 (74·2% [95% CI 63·8-82·9]) patients in the 60 Gy group were alive, compared with 39 (48·1% [36·9-59·5]) patients in the 45 Gy group (odds ratio 3·09 [95% CI 1·62-5·89]; p=0·0005). The most common grade 3-4 adverse events were neutropenia (72 [81%] of 89 patients in the 60 Gy group vs 62 [81%] of 77 patients in the 45 Gy group), neutropenic infections (24 [27%] vs 30 [39%]), thrombocytopenia (21 [24%] vs 19 [25%]), anaemia (14 [16%] vs 15 [20%]), and oesophagitis (19 [21%] vs 14 [18%]). There were 55 serious adverse events in 38 patients in the 60 Gy group and 56 serious adverse events in 44 patients in the 45 Gy group. There were three treatment-related deaths in each group (one neutropenic fever, one aortic dissection, and one pneumonitis in the 60 Gy group; one thrombocytic bleeding, one cerebral infarction, and one myocardial infarction in the 45 Gy group).

Interpretation: The higher radiotherapy dose of 60 Gy resulted in a substantial survival improvement compared with 45 Gy, without increased toxicity, suggesting that twice-daily thoracic radiotherapy of 60 Gy is an alternative to existing schedules.

Funding: The Norwegian Cancer Society, The Liaison Committee for Education, Research and Innovation in Central Norway, the Nordic Cancer Union, and the Norwegian University of Science and Technology.
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http://dx.doi.org/10.1016/S1470-2045(20)30742-7DOI Listing
March 2021

Tumor-site specific geometric distortions in high field integrated magnetic resonance linear accelerator radiotherapy.

Phys Imaging Radiat Oncol 2020 Jul 19;15:100-104. Epub 2020 Aug 19.

Laboratory of Radiation Physics, Odense University Hospital, Kløvervænget 19, 5000 Odense C, Denmark.

Magnetic resonance imaging (MRI) has exquisite soft-tissue contrast and is the foundation for image guided radiotherapy (IGRT) with integrated magnetic resonance linacs. However, MRI suffers from geometrical distortions. In this study the MRI system- and patient-induced geometric distortion at four different tumor-sites was investigated: adrenal gland (7 patients), liver (4 patients), pancreas (6 patients), prostate (20 patients). Maximum level of total distortion within the gross-tumor-volume (GTV) was 0.96 mm with no significant difference between abdominal patients (adrenal gland, liver, pancreas) and pelvic patients (prostate). Total tumor-site specific distortion depended on location in the field-of-view and increased with the distance to MRI iso-center.
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http://dx.doi.org/10.1016/j.phro.2020.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807890PMC
July 2020

Prospectively scored pulmonary toxicities in non-small cell lung cancer: Results from a randomized phase II dose escalation trial.

Clin Transl Radiat Oncol 2021 Mar 26;27:8-14. Epub 2020 Nov 26.

Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.

Purpose: Prospectively scored radiation pneumonitis (RP) observed in a national, randomized phase II dose-escalation trial for patients with locally advanced non-small cell lung cancer (NSCLC) was investigated.

Methods: Patients with stage IIB-IIIB histologically proven NSCLC were treated with concomitant chemo-radiotherapy (oral Vinorelbine 3times/week) at 60 Gy/30fx (A-59pts) and 66 Gy/33fx (B-58pts) from 2009 to 2013 at five Danish RT centers. Grade 2 RP (CTCAEv3.0) was investigated with univariate analysis for association with clinical and dosimetric parameters, including dyspnea and cough at baseline and during RT. Multivariable logistic regression and Cox regression with regularization were used to find a multivariable model for RP ≥ G2.

Results: Despite a tendency of higher mean lung dose in the high-dose arm (median[range] A = 14.9 Gy[5.8,23.1], B = 17.5 Gy[8.6,24.8], p = 0.075), pulmonary toxicities were not significantly different (RP ≥ G2 41%(A) and 52%(B), p = 0.231). A Kaplan Meier analysis of the time to RP ≥ G2 between the two arms did not reach statistical significance (p = 0.180). Statistically significant risk factors for RP ≥ G2 were GTV size (OR = 2.091/100 cm3, p = 0.002), infection at baseline or during RT (OR = 8.087, p = 0.026), dyspnea at baseline (OR = 2.184, p = 0.044) and increase of cough during RT (OR = 2.787, p = 0.008). In the multivariable logistic regression and the Cox regression analysis, the deviances of the most predictive models were within one standard deviation of the null model.

Conclusion: No statistical difference between the high- and low dose arm was found in the risk of developing RP. The univariate analysis identified target volume, infection, dyspnea at baseline, and increase of cough during RT as risk factors for RP. The number of patients was too small to establish a statistically sound multivariable model.
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http://dx.doi.org/10.1016/j.ctro.2020.11.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770437PMC
March 2021

End-to-end validation of the geometric dose delivery performance of MR linac adaptive radiotherapy.

Phys Med Biol 2021 Feb 12;66(4):045034. Epub 2021 Feb 12.

Laboratory of Radiation Physics, Department of Oncology, Odense University Hospital, Odense, Denmark. Department of Clinical Research, University of Southern Denmark, Odense, Denmark.

The clinical introduction of hybrid magnetic resonance (MR) guided radiotherapy (RT) delivery systems has led to the need to validate the end-to-end dose delivery performance on such machines. In the current study, an MR visible phantom was developed and used to test the spatial deviation between planned and delivered dose at two 1.5 T MR linear accelerator (MR linac) systems, including pre-treatment imaging, dose planning, online imaging, image registration, plan adaptation, and dose delivery. The phantom consisted of 3D printed plastic and MR visible silicone rubber. It was designed to minimise air gaps close to the radiochromic film used as a dosimeter. Furthermore, the phantom was designed to allow submillimetre, reproducible positioning of the film in the phantom. At both MR linac systems, 54 complete adaptive, MR guided RT workflow sessions were performed. To test the dose delivery performance of the MR linac systems in various adaptive RT (ART) scenarios, the sessions comprised a range of systematic positional shifts of the phantom and imaging or plan adaptation conditions. In each workflow session, the positional translation between the film and the adaptive planned dose was determined. The results showed that the accuracy of the MR linac systems was between 0.1 and 0.9 mm depending on direction. The highest mean deviance observed was in the posterior-anterior direction, and the direction of the error was consistent between centres. The precision of the systems was related to whether the workflow utilized the internal image registration algorithm of the MR linac. Workflows using the internal registration algorithm led to a worse precision (0.2-0.7 mm) compared to workflows where the algorithm was decoupled (0.2 mm). In summary, the spatial deviation between planned and delivered dose of MR-guided ART at the two MR linac systems was well below 1 mm and thus acceptable for clinical use.
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http://dx.doi.org/10.1088/1361-6560/abd3edDOI Listing
February 2021

[Thermal ablation of brain tumours].

Ugeskr Laeger 2020 Jul;182(28)

The diagnosis of a malignant brain tumour is often associated with a poor prognosis. Current treatment is surgical resection followed by radio-chemotherapy. Surgical resection is most favourable in relation to survival time. Unfortunately, many patients are not suitable for surgical resection, due to inoperable tumour location or the patients' poor state. Minimally invasive thermal ablation may pose an interesting new treatment alternative. In this review, we describe the evolution, the underlying physiology and the clinical applications of cryo- and laser-induced thermal therapy of primary and secondary brain tumours.
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July 2020

Delineation of whole heart and substructures in thoracic radiation therapy: National guidelines and contouring atlas by the Danish Multidisciplinary Cancer Groups.

Radiother Oncol 2020 09 13;150:121-127. Epub 2020 Jun 13.

Danish Centre for Particle Therapy, Aarhus, Denmark; Odense University Hospital, Laboratory of Radiation Physics, Odense, Denmark.

Background And Purpose: This study presents Danish consensus guidelines for delineation of the heart and cardiac substructures across relevant Danish Multidisciplinary Cancer Groups.

Material And Methods: Consensus guidelines for the heart and cardiac substructures were reached among 15 observers representing the radiotherapy (RT) committees of four Danish Multidisciplinary Cancer Groups. The guidelines were validated on CT scans of 12 patients, each with five independent contour sets. The Sørensen-Dice similarity coefficient (DSC), the distance between the centers of the arteries and the mean surface distance were used to evaluate the inter-observer variation.

Results: National guidelines for contouring the heart and cardiac substructures were achieved. The median DSC was 0.78-0.96 for the heart and the four cardiac chambers. For the four substructures of the left ventricle, the median DSC was 0.35-0.57. The coronary arteries were contoured in ten segments, with the best agreement for the left anterior descending coronary artery segments, with a median distance between the arteries ranging from 2.4-4.4 mm. The median variation was 3.7-12.8 mm for the right coronary artery segments and 3.7-6.2 mm for the left circumflex coronary artery segments, with the most pronounced inter-observer variation in the distal segment for all three coronary arteries.

Conclusion: National guidelines for contouring the heart and cardiac substructures were developed across relevant Danish Multidisciplinary Cancer Groups, where RT dose to the heart is of concern. The inter-observer contour overlap was best for the heart and chambers and decreased for smaller structures.
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http://dx.doi.org/10.1016/j.radonc.2020.06.015DOI Listing
September 2020

Surveillance With PET/CT and Liquid Biopsies of Stage I-III Lung Cancer Patients After Completion of Definitive Therapy: A Randomized Controlled Trial (SUPER).

Clin Lung Cancer 2020 03 21;21(2):e61-e64. Epub 2019 Nov 21.

Department of Nuclear Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; PET Center, School of Biomedical Engineering and Imaging Sciences Kings College London, St Thomas' Hospital, London, UK. Electronic address:

Despite increased focus on prevention as well as improved treatment possibilities, lung cancer remains among the most frequent and deadliest cancer diagnoses worldwide. Even lung cancer patients treated with curative intent have a high risk of relapse, leading to a dismal prognosis. More knowledge on the efficacy of surveillance with both current and new technologies as well as on the impact on patient treatment, quality of life, and survival are urgently needed. We therefore designed a randomized phase 3 trial. In one arm, every other computed tomography (CT) scan is replaced by positron emission tomography/CT, the other arm is the standard follow-up scheme with CT. The standard arm is identical to the current national Danish follow-up program. The primary endpoint is to compare the number of relapses treatable with curative intent in the 2 arms. We aim to include 750 patients over a 3-year period. Additionally, we will test the feasibility of noninvasive lung cancer diagnostics and surveillance in the form of circulating tumor DNA analysis. For this purpose, blood samples are collected before treatment and at each following control. The blood samples are stored in a biobank for later analysis and will not be used for guiding patient treatment decisions.
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http://dx.doi.org/10.1016/j.cllc.2019.11.002DOI Listing
March 2020

Survival after stereotactic radiotherapy in patients with early-stage non-small cell lung cancer.

Acta Oncol 2019 Oct 4;58(10):1399-1403. Epub 2019 Jul 4.

Department of Oncology, Odense University Hospital , Odense , Denmark.

Stereotactic radiotherapy (SBRT) is the treatment of choice for inoperable early stage non-small cell lung cancer (NSCLC). We report analyses of the influence of age on survival after SBRT. : From 2005 to 2017, 544 previously un-irradiated patients with early stage NSCLC had SBRT. The data were analyzed in four age groups: A: -69 (176 pts), B: 70-74 (115 pts), C: 75-79 (131 pts) and D: 80 years or older (122 pts). Two SBRT dose regimes were used: 45 Gy/3F ( = 103) and 66 Gy/3F ( = 441). All patients had a follow up (time to censoring, FU) of at least 16 months, the median FU being 48.0 months. The median age was 74.4 years. The overall survival (OS) was associated with age. The median OS was 50.7, 45.9, 45.4 and 33.0 months, and the 5-year OS was 45%, 32%, 33% and 18% in groups A, B, C and D, respectively. No difference was found between groups B and C, while OS in group A was significantly better than remaining groups, and the OS in group D significantly poorer. In multivariable analyses, OS was heavily influenced by age, Charlson's comorbidity index (CCI) and performance status (PS). For lung cancer-specific survival (LCSS), only increasing tumor diameter and PS were associated with poor survival. The OS was influenced by age, but the study suggests that a cut point of 75 year is inappropriate in evaluating the effect of old age on survival. Poor PS was associated with poor OS. CCI influenced OS, but not LCSS, which was only affected by PS and tumor size.
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http://dx.doi.org/10.1080/0284186X.2019.1631476DOI Listing
October 2019

The effect of tumor laterality on survival for non-small cell lung cancer patients treated with radiotherapy.

Acta Oncol 2019 Oct 4;58(10):1393-1398. Epub 2019 Jul 4.

Department of Clinical Research, University of Southern Denmark , Odense , Denmark.

The treatment of choice for patients with locally advanced non-small cell lung cancer (LA-NSCLC) in good performance status is definitive radiotherapy (RT), the five-year survival being approximately 25-30%. Advances in the diagnostic procedures and treatment modalities in NSCLC have increased the overall survival, making identifying factors with impact on survival increasingly relevant. Recent research indicates that tumor laterality has impact on the survival of patients with LA-NSCLC treated with definitive RT. The aim of this study was to investigate whether tumor laterality impacted overall survival. All patients with stage IIa-IIIb NSCLC planned for curative intended RT from 2008 to 2013 at Odense University Hospital were analyzed to compare overall survival of patients with right-sided vs. left-sided tumors. Log-rank test was performed to test for differences in survival rates and Cox regression analyses to test for possible confounders. No patients were lost to follow-up. In total, 164 patients had a tumor in the right lung and 118 had tumor in the left lung. All patients had at least 4.5 years' follow-up. Median overall survival was 19 months (right) and 22.5 months (left)  = .729. Three-year overall survival was 31% (right) and 35% (left). In Cox regression analyses age, performances status and total mean lung dose were statistically significant with a hazard ratio (HR) = 1.03 (95% Cl: 1.01-1.05), HR = 1.60 (95% Cl: 1.12-2.28), and HR = 1.11 (95% Cl: 1.06-1.16), respectively. This study did not verify that laterality has a significant impact on survival in LA-NSCLC patients treated with curative intended RT.
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http://dx.doi.org/10.1080/0284186X.2019.1629011DOI Listing
October 2019

First clinical experiences with a high field 1.5 T MR linac.

Acta Oncol 2019 Oct 26;58(10):1352-1357. Epub 2019 Jun 26.

Laboratory of Radiation Physics, Odense University Hospital , Odense , Denmark.

A 1.5 T MR Linac (MRL) has recently become available. MRL treatment workflows (WF) include online plan adaptation based on daily MR images (MRI). This study reports initial clinical experiences after five months of use in terms of patient compliance, cases, WF timings, and dosimetric accuracy. Two different WF were used dependent on the clinical situation of the day; Adapt To Position WF (ATP) where the reference plan position is adjusted rigidly to match the position of the targets and the OARs, and Adapt To Shape WF (ATS), where a new plan is created to match the anatomy of the day, using deformable image registration. Both WFs included three 3D MRI scans for plan adaptation, verification before beam on, and validation during IMRT delivery. Patient compliance and WF timings were recorded. Accuracy in dose delivery was assessed using a cylindrical diode phantom. Nineteen patients have completed their treatment receiving a total of 176 fractions. Cases vary from prostate treatments (60Gy/20F) to SBRT treatments of lymph nodes (45 Gy/3F) and castration by ovarian irradiation (15 Gy/3F). The median session time (patient in to patient out) for 127 ATPs was 26 (21-78) min, four fractions lasted more than 45 min due to additional plan adaptation. For the 49 ATSs a median time of 12 (1-24) min was used for contouring resulting in a total median session time of 42 (29-91) min. Three SBRT fractions lasted more than an hour. The time on the MRL couch was well tolerated by the patients. The median gamma pass rate (2 mm,2% global max) for the adapted plans was 99.2 (93.4-100)%, showing good agreement between planned and delivered dose. MRL treatments, including daily MRIs, plan adaptation, and accurate dose delivery, are possible within a clinically acceptable timeframe and well tolerated by the patients.
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http://dx.doi.org/10.1080/0284186X.2019.1627417DOI Listing
October 2019

Efficacy and safety of immune checkpoint inhibitors in a Danish real life non-small cell lung cancer population: a retrospective cohort study.

Acta Oncol 2019 Jul 12;58(7):953-961. Epub 2019 May 12.

a Department of Clinical Oncology , Odense University Hospital , Odense , Denmark.

To investigate effect and toxicity of immune checkpoint inhibition (ICI) in a Danish real-life non-small cell lung cancer (NSCLC) population. By including patients underrepresented in clinical trials, such as those with brain metastasis (BM), higher age, more comorbidity and poorer performance status (ECOG), comparison of unselected patients to clinical trial populations is possible. Real life data were gathered from 118 consecutive NSCLC patients with incurable NSCLC treated with ICI at the Department of Oncology at the University Hospital of Odense, Denmark from September 2015 to April 2018. Immune-related adverse events (irAEs) grades 3-5 were registered prospectively during the same period. Additional patient related data were obtained retrospectively from patients' files. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier estimates, the log-rank test and cox regression analysis performed for factors affecting survival. Median age for patients was 66 years (IQR 59-71) and 62 years (range: 55-64) for those with BM. Females 63%; adenocarcinoma (AC)/squamous/others 69%/23%/8%; ECOG ≥ 2 10%; bone/brain/liver metastases 36%/18%/15%; PD-L1 (TPS) <1%/ ≥ 1%/ ≤ 49%/ ≥ 50%/NR: 3%/14%/68%/15%; baseline autoimmunity 10%, Charlson's Comorbidity Index Score (CCIS) ≥ 2 39%, treatment line: 1st/2nd/ ≥ 3rd 39%/30%/31%. Median OS for patients receiving ICI in ≥2 line was 11.5 months versus not reached in first line (HR 2.6, [95% CI: 1.3-5.0],  = .005). For patients with BM, the median OS was 8.2 months (HR 1.38, [95% CI: 0.7-2.5],  = .37). Twenty-four percent of patients terminated ICI due to irAE grades 3-5 alone (grade 5,   =  1), which were not associated with higher age or BM. OS and PFS were comparable to clinical trial reports. Long-lasting remission is also possible in patients with BM. Real-life populations have higher rates of irAE grades 3 and 4 than reported in clinical trials, but it does not seem to impact median OS.
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http://dx.doi.org/10.1080/0284186X.2019.1615636DOI Listing
July 2019

Impact of comprehensive geriatric assessment on quality of life, overall survival, and unplanned admission in patients with non-small cell lung cancer treated with stereotactic body radiotherapy.

J Geriatr Oncol 2018 11 3;9(6):575-582. Epub 2018 Jun 3.

Department of Oncology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark; Institute of Clinical Research, University of Southern Denmark, Winsløwparken, 5000 Odense C, Denmark. Electronic address:

Objectives: Overall survival ﴾OS﴿ for patients with localized non-small cell lung cancer ﴾NSCLC﴿ treated with stereotactic body radiotherapy ﴾SBRT﴿ is poorer than for patients undergoing surgery. Patients who undergo SBRT are often ineligible for surgery due to significant comorbidities that can impact their mortality. A comprehensive geriatric assessment (CGA) that identifies and treats aging related comorbidities could improve OS and quality of life (QoL). This randomized study investigated if a CGA added to SBRT impacts QoL, survival, and unplanned admissions.

Materials And Methods: From January 2015 to June 2016, 51 patients diagnosed with T1-2N0M0 NSCLC treated with SBRT were enrolled. The patients were randomized 1:1 to receive SBRT +/- CGA. EuroQoL Group 5D (EQ-5D) health index and visual analogue scale (VAS) scores were assessed at start of SBRT, at five weeks, and every third month for a year after SBRT.

Results: There were 26 and 25 patients randomized to receive ± CGA, respectively. The repeated measures one-way analysis of variance (ANOVA) test of the EQ-5D health index and VAS scores did not show statistically significant differences between groups. For the EQ-5D VAS scores at twelve months follow-up there was a small difference between the groups although not statistically significant. Even though more patients deceased in the no-CGA group, no statistically significant difference in survival rates and unplanned admission rate was observed between groups.

Conclusion: In patients with localized NSCLC treated with SBRT, a CGA did not impact the overall QoL, the prevalence/length of unplanned admissions, or survival. There was an indication of small differences in QoL and survival in the data, but such differences can only be validated in larger studies.
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http://dx.doi.org/10.1016/j.jgo.2018.05.009DOI Listing
November 2018

Heterogeneous FDG-guided dose-escalation for locally advanced NSCLC (the NARLAL2 trial): Design and early dosimetric results of a randomized, multi-centre phase-III study.

Radiother Oncol 2017 08 5;124(2):311-317. Epub 2017 Jul 5.

Department of Oncology, Vejle Hospital, Vejle, Denmark; Leeds Institute of Cancer and Pathology, University of Leeds and Leeds Cancer Centre, St James's University Hospital, Leeds, UK.

Background And Purpose: Local recurrence is frequent in locally advanced NSCLC and is primarily located in FDG-avid parts of tumour and lymph nodes. Aiming at improving local control without increasing toxicity, we designed a multi-centre phase-III trial delivering inhomogeneous dose-escalation driven by FDG-avid volumes, while respecting normal tissue constraints and requiring no increase in mean lung dose. Dose-escalation driven by FDG-avid volumes, delivering mean doses of 95Gy (tumour) and 74Gy (lymph nodes), was pursued and compared to standard 66Gy/33F plans.

Material And Methods: Dose plans for the first thirty patients enroled were analysed. Standard and escalated plans were created for all patients, blinded to randomization, and compared for each patient in terms of the ability to escalate while protecting normal tissue.

Results: The median dose-escalation in FDG-avid areas was 93.9Gy (tumour) and 73.0Gy (lymph nodes). Escalation drove the GTV and CTV to mean doses for the tumour of 87.5Gy (GTV-T) and 81.3Gy (CTV-T) in median. No significant differences in mean dose to lung and heart between standard and escalated were found, but small volumes of e.g. the bronchi received doses between 66 and 74Gy due to escalation.

Conclusions: FDG-driven inhomogeneous dose-escalation achieves large increment in tumour and lymph node dose, while delivering similar doses to normal tissue as homogenous standard plans.
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http://dx.doi.org/10.1016/j.radonc.2017.06.022DOI Listing
August 2017

A randomized phase II trial of concurrent chemoradiation with two doses of radiotherapy, 60Gy and 66Gy, concomitant with a fixed dose of oral vinorelbine in locally advanced NSCLC.

Radiother Oncol 2017 05 11;123(2):276-281. Epub 2017 Apr 11.

Department of Oncology, Odense University Hospital, Denmark.

Introduction: In order to test the best performing radiation dose with a convenient chemotherapy schedule of an oral formulation of radio-sensitizing vinorelbine in inoperable locally advanced non-small cell lung cancer (NSCLC), we performed a randomized phase II trial based on a "pick the winner" design.

Methods: After 2 cycles of neoadjuvant chemotherapy, 117 patients with NSCLC stage IIB-IIIB in performance status 0-1 were randomized to radiotherapy 60Gy/30 fractions or 66Gy/33 fractions concurrent with a fixed dose of oral vinorelbine 50mg administered 3 times weekly. The primary endpoint was local progression free interval. A scheduled FDG-PET-CT-scan was performed 9months after randomization. The study was registered at ClinicalTrials.gov (NCT 00887783).

Results: Both arms were well tolerated. The local progression free interval at 9months was 54% in the 60Gy arm and 59% in the 66Gy arm (log rank test p=0.55). There was no statistically significant difference in overall survival. The median survival was 23.3 and 23.7months in the 60 and 66Gy arm, respectively. No significant difference in toxicity was observed.

Conclusion: Both 60 and 66Gy administered concomitant with oral vinorelbine showed similar local control and overall survival, and was well tolerated. The pick the winner design choose 66Gy as the winning arm.
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http://dx.doi.org/10.1016/j.radonc.2017.03.017DOI Listing
May 2017

Extent and computed tomography appearance of early radiation induced lung injury for non-small cell lung cancer.

Radiother Oncol 2017 04 1;123(1):93-98. Epub 2017 Mar 1.

Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Laboratory of Radiation Physics, Odense University Hospital, Odense, Denmark.

Background And Purpose: The present study investigates the extent and appearance of radiologic injury in the lung after radiotherapy for non-small cell lung cancer (NSCLC) patients and correlates radiologic response with clinical and dosimetric factors.

Methods And Materials: Eligible follow-up CT scans acquired up to six months after radiotherapy were evaluated for radiologic injuries in 220 NSCLC patients. Radiologic injuries were divided into three categories: (1) interstitial changes, (2) ground-glass opacity, or (3) consolidation. The relationship between the fraction of injured lung of each category and clinical or dosimetric factors was investigated.

Results: Radiological injuries of category 1-3 were found in 67%, 52%, and 51% of the patients, and the mean (and maximum) fraction of injured lung was 4.4% (85.9%), 2.4% (46.0%), and 2.1% (22.9%), respectively. Traditional lung dose metrics and time to follow-up predicted lung injury of all categories. Older age increased the risk of interstitial changes and current smoking reduced the risk of consolidation in the lung.

Conclusion: Radiologic injuries were frequently found in follow-up CT scans after radiotherapy for NSCLC patients. The risk of a radiologic response increased with increasing time and lung dose metrics, and depended on patient age and smoking status.
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http://dx.doi.org/10.1016/j.radonc.2017.02.001DOI Listing
April 2017

Comparison of survival of chronic obstructive pulmonary disease patients with or without a localized non-small cell lung cancer.

Lung Cancer 2016 10 11;100:90-95. Epub 2016 Aug 11.

Department of Oncology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark; Institute of Clinical Research, University of Southern Denmark, Winsløwparken 19.3, 5000 Odense C, Denmark. Electronic address:

Objectives: Chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) are often co-existing diseases with poor prognosis. The aim of this study was to compare survival in COPD patients with localized NSCLC treated with stereotactic body radiotherapy (NSCLC group) with COPD patients without a malignant diagnosis (non-malignant group).

Materials And Methods: The NSCLC group was prospectively recorded at the Department of Oncology from 2007 to 2013. The non-malignant group was selected among patients referred to the Department of Respiratory Medicine from 2005 until 2011 suspected of thoracic malignancy but without the malignant diagnosis maintained.

Results: In a propensity score matched comparison the median overall survival was 53 vs. 71 months in the NSCLC and non-malignant groups, respectively (p<0.001). Subgroup analyses showed survival for patients with mild/moderate COPD was affected statistically significant with a higher mortality rate by a diagnosis of localized NSCLC with hazard ratio=2.62 (95% CI: 1.47-4.68) while an insignificant higher mortality rate with hazard ratio=1.22 (95% CI: 0.71-2.08) was found in patient with severe/very severe COPD.

Conclusion: Despite the serious prognosis of COPD, a localized NSCLC diagnosis negatively affects survival in COPD patients. However, stereotactic body radiotherapy should still be considered for COPD patients diagnosed with localized NSCLC.
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http://dx.doi.org/10.1016/j.lungcan.2016.08.006DOI Listing
October 2016

Acute esophagitis for patients with local-regional advanced non small cell lung cancer treated with concurrent chemoradiotherapy.

Radiother Oncol 2016 Mar 20;118(3):465-70. Epub 2016 Jan 20.

Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Oncology, Odense University Hospital, Denmark. Electronic address:

Purpose: Esophagitis is common in patients treated with definitive radiotherapy for local-regional advanced non small cell lung cancer (NSCLC). The purpose of this study was to estimate the dose-effect relationship using clinical and dosimetric parameters in patients receiving intensity modulated radiotherapy (IMRT) and concomitant chemotherapy (CCT).

Methods: Between 2009 and 2013, 117 patients with stages IIB-IIIB NSCLC were treated in a multicenter randomized phase II trial with 2 cycles of induction chemotherapy followed by IMRT and CCT. The esophagitis was prospectively scored using the Common Toxicity Criteria 3.0. Clinical and dosimetric variables were analyzed for the correlation with grade ⩾2 esophagitis through logistic regression.

Results: Grade 2 esophagitis was experienced by 31 (27%). All models including gender, institution, a dosimetric parameter and a position parameter were significantly associated with esophagitis. The two models using the relative esophagus volume irradiated above 40 Gy (V40, OR=2.18/10% volume) or the length of esophagus irradiated above 40 Gy (L40, OR=4.03/5 cm) were optimal. The upper part of esophagus was more sensitive and females experienced more toxicity than men.

Conclusion: V40 and L40 were most effective dosimetric predictors of grade ⩾2 esophagitis. The upper part of esophagus was more sensitive.
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http://dx.doi.org/10.1016/j.radonc.2016.01.007DOI Listing
March 2016

Trends in lung cancer in elderly in Denmark, 1980-2012.

Acta Oncol 2016 15;55 Suppl 1:46-51. Epub 2016 Jan 15.

a Department of Oncology , Odense University Hospital , Odense , Denmark ;

Background: Lung cancer is an increasing problem in the older patient population due to the improvement in life expectation of the Western population. In this study we examine trends in lung cancer incidence and mortality in Denmark from 1980 to 2012 with special focus on the elderly.

Material And Methods: Lung cancer was defined as ICD-10 codes C33-34. Data derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence, and relative survival in the Nordic countries, where the Danish data were delivered from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up for death or emigration until the end of 2013.

Results: In 2012, about 50% of lung cancers were diagnosed among persons aged 70 years or more. For men and women older than 75 years the incidence rates have been increasing and for those aged 80-84 years, the rates have doubled since 1980. Due to the poor survival, similar trends were seen in mortality rates. Over the period, the one-year relative survival rates almost doubled in patients aged 70 years or more, but still only 25% of the patients aged 80-89 years survived their lung cancer for one year.

Conclusion: The incidence of lung cancer is closely linked to the pattern of tobacco smoking with the differences between gender and age groups reflecting smoking behavior in birth cohorts. Elderly patients with lung cancer are a heterogeneous group in whom treatment should be offered according to comorbidity and a geriatric assessment.
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http://dx.doi.org/10.3109/0284186X.2015.1114676DOI Listing
September 2016

Planned FDG PET-CT Scan in Follow-Up Detects Disease Progression in Patients With Locally Advanced NSCLC Receiving Curative Chemoradiotherapy Earlier Than Standard CT.

Medicine (Baltimore) 2015 Oct;94(43):e1863

From the Southern Medical University (YP, Y-LW), Department of Radiation Oncology, Guangdong General Hospital & Guangdong Academy of Medical Science, Guangzhou, P.R. China (YP), Department of Oncology, Odense University Hospital (YP, TS, OH), Institution of Clinical Research, University of Southern Denmark (YP, CB, TS, OH), Laboratory of Radiation Physics, Odense University Hospital (CB), Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark (HP); and Guangdong Lung Cancer Institute, Guangzhou, P.R. China (Y-LW).

The role of positron emission tomography-computed tomography (PET-CT) in surveillance of patients with nonsmall cell lung cancer (NSCLC) treated with curatively intended chemoradiotherapy remains controversial. However, conventional chest X-ray and computed tomography (CT) are of limited value in discriminating postradiotherapy changes from tumor relapse. The aim of this study was to evaluate the clinical value of PET-CT scan in the follow-up for patients with locally advanced (LA) NSCLC receiving concomitant chemoradiotherapy (CCRT).Between 2009 and 2013, eligible patients with stages IIB-IIIB NSCLC were enrolled in the clinical trial NARLAL and treated in Odense University Hospital (OUH). All patients had a PET-CT scan scheduled 9 months (PET-CT9) after the start of the radiation treatment in addition to standard follow-up (group A). Patients who presented with same clinical stage of NSCLC and received similar treatment, but outside protocol in OUH during this period were selected as control group (group B). Patients in group B were followed in a conventional way without PET-CT9. All patients were treated with induction chemotherapy followed by CCRT.Group A included 37 and group B 55 patients. The median follow-up was 16 months. Sixty-six (72%) patients were diagnosed with progression after treatment. At the time of tumor progression, patients in group A had better performance status (PS) than those in group B (P = 0.02). Because of death (2 patients), poor PS (3) or retreatment of relapse (9), only 23 patients had PET-CT9 in group A. Eleven (48%) patients were firstly diagnosed with progression by PET-CT9 without any clinical symptoms of progression. The median progression-free survival (PFS) was 8.8 months in group A and 12.5 months in group B (P = 0.04). Hazard function PFS showed that patients in group A had higher risk of relapse than in group B.Additional FDG PET-CT scan at 9 months in surveillance increases probability of early detection of disease progression in advanced NSCLC patients treated with curatively intended CCRT.
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http://dx.doi.org/10.1097/MD.0000000000001863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985411PMC
October 2015

Changes in pulmonary function after definitive radiotherapy for NSCLC.

Radiother Oncol 2015 Oct 8;117(1):23-8. Epub 2015 Oct 8.

Department of Oncology, Odense University Hospital, Denmark; Institute of Clinical Research, University of Southern Denmark, Denmark.

Introduction: The objective of this study was to identify factors associated with early and long-term pulmonary function (PF) changes after definitive radiotherapy for NSCLC patients. PF was measured by spirometry i.e. forced expiratory volume in 1s (FEV1), and forced vital capacity (FVC).

Materials: Early (within the first year) PF change was analyzed in 211 patients with 986 pairs of PF-tests (PFTs). Long-term PF change was analyzed relative to the PF at 12months after radiotherapy in 106 patients (1286 PFTs). To investigate the impact of patient and treatment related factors on PF, they were tested as covariates in multivariable analysis.

Results: Early PF change was quantified at six months after the start of radiotherapy. Smoking status and increasing V60 was associated with a significant decrease in PF, whereas smoking was protective. In addition, neoadjuvant chemotherapy had a negative impact on FVC. Long-term FEV1 and FVC were analyzed using linear regression. Treatment year and V60 had a significant impact on loss of FEV1. V60 had a significant impact on FVC changes.

Conclusion: In this study, early PF change reached a plateau at 6months after the start of radiotherapy for NSCLC. Large volume of lung receiving high dose was associated with long-term FEV1 change.
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http://dx.doi.org/10.1016/j.radonc.2015.09.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537552PMC
October 2015

Prediction of lung density changes after radiotherapy by cone beam computed tomography response markers and pre-treatment factors for non-small cell lung cancer patients.

Radiother Oncol 2015 Oct 6;117(1):17-22. Epub 2015 Aug 6.

Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Laboratory of Radiation Physics, Odense University Hospital, Denmark.

Background And Purpose: This study investigates the ability of pre-treatment factors and response markers extracted from standard cone-beam computed tomography (CBCT) images to predict the lung density changes induced by radiotherapy for non-small cell lung cancer (NSCLC) patients.

Methods And Materials: Density changes in follow-up computed tomography scans were evaluated for 135 NSCLC patients treated with radiotherapy. Early response markers were obtained by analysing changes in lung density in CBCT images acquired during the treatment course. The ability of pre-treatment factors and CBCT markers to predict lung density changes induced by radiotherapy was investigated.

Results: Age and CBCT markers extracted at 10th, 20th, and 30th treatment fraction significantly predicted lung density changes in a multivariable analysis, and a set of response models based on these parameters were established. The correlation coefficient for the models was 0.35, 0.35, and 0.39, when based on the markers obtained at the 10th, 20th, and 30th fraction, respectively.

Conclusions: The study indicates that younger patients without lung tissue reactions early into their treatment course may have minimal radiation induced lung density increase at follow-up. Further investigations are needed to examine the ability of the models to identify patients with low risk of symptomatic toxicity.
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http://dx.doi.org/10.1016/j.radonc.2015.07.021DOI Listing
October 2015

In reply to Yamazaki et al.

Int J Radiat Oncol Biol Phys 2015 Jan;91(1):245-6

Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland.

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http://dx.doi.org/10.1016/j.ijrobp.2014.09.001DOI Listing
January 2015

Age dependent prognosis in concurrent chemo-radiation of locally advanced NSCLC.

Acta Oncol 2015 Mar 7;54(3):333-9. Epub 2014 Oct 7.

Department of Oncology, Odense University Hospital , Odense , Denmark.

Background: Clinical trials indicate that the benefit of adding concurrent chemotherapy to radiotherapy of locally advanced non-small cell lung cancer (NSCLC) for fit elderly is similar to the benefit for younger patients. However, since elderly patients are under-represented in most trials, the results might be due to selection bias, thus reports from a cohort of consecutively treated patients are warranted. The current single institution study reports on the influence of age on survival of locally advanced NSCLC patients treated with radiotherapy combined with or without concurrent chemotherapy.

Material And Methods: Altogether, 478 patients completed radical radiotherapy in doses of 60-66 Gy/30-33 fractions from 1995 to June 2012; 137 of the patients had concurrent chemotherapy. The data was analyzed in age groups<60, 60-69, and ≥70 years.

Results: In the analyses of overall and lung cancer specific survival the hazard ratio was related to the use of concurrent chemotherapy was 0.49 (95% CI 0.29; 0.82), 0.68 (95% CI 0.48; 0.98) and 1.01 (95% CI 0.67; 1.51) for the age groups<60, 60-69, and ≥70, respectively.

Conclusion: Use of concurrent chemotherapy to radiotherapy of locally advanced NSCLC was associated with a survival benefit in patient younger than 70 years which was not the case for patients older than 70 years, indicating the need to be careful when selecting elderly patients for concurrent chemo-radiation.
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http://dx.doi.org/10.3109/0284186X.2014.958529DOI Listing
March 2015

Adjuvant chemotherapy compliance is not superior after thoracoscopic lobectomy.

Ann Thorac Surg 2014 Aug 4;98(2):411-5; discussion 415-6. Epub 2014 Jun 4.

Department of Cardiothoracic Surgery, Odense University Hospital, Odense, Denmark; Danish Lung Cancer Registry, Odense University Hospital, Odense, Denmark.

Background: It is generally assumed that patient compliance with adjuvant chemotherapy is superior after video-assisted thoracoscopic surgery compared with open lobectomy for non-small cell lung cancer (NSCLC). The level of evidence for this assumption, however, is limited to single-institution, case-control studies. We used a complete national lung cancer registry.

Methods: For better comparison and reduction of selection bias, we analyzed only patients who underwent standard lobectomy for clinical stage 1 NSCLC and subsequently had unsuspected lymph node metastases discovered at final histopathology. A clinical oncologist, who was blinded to the surgical approach, reviewed all medical oncology charts for types of adjuvant chemotherapy, reasons for not initiating or stopping treatment, number of cycles delivered, and time interval from surgery to initial chemotherapy.

Results: During a 6-year period (2007 to 2012), 1,968 patients underwent standard lobectomy for clinical stage 1 NSCLC by video-assisted thoracoscopic surgery (n=990; 50.3%) or thoracotomy (n=978; 49.7%). Unsuspected nodal upstaging was later found in 341 patients (17.3%), and 313 were analyzed: 189 patients (60.4%) received adjuvant chemotherapy and 121 (38.7%) completed all four cycles. Ordinal logistic regression revealed that chemotherapy compliance (none, partial, and full chemotherapy) was significantly reduced by the patient's age (p<0.001) and comorbidity index (p=0.003) but increased with N2 status (p=0.02). No significant difference between video-assisted thoracoscopic surgery and thoracotomy was seen regarding chemotherapy compliance (p=0.17), number of chemotherapy cycles (p=0.60), or time from surgery to chemotherapy (p = 0.41).

Conclusions: Complete national data do not support the widespread assumption that adjuvant chemotherapy compliance is superior after thoracoscopic lobectomy for NSCLC. Instead, significant predictors of chemotherapy compliance are patient's age, comorbidity, and pathologic N status.
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http://dx.doi.org/10.1016/j.athoracsur.2014.04.026DOI Listing
August 2014

Locoregional control of non-small cell lung cancer in relation to automated early assessment of tumor regression on cone beam computed tomography.

Int J Radiat Oncol Biol Phys 2014 Jul 24;89(4):916-23. Epub 2014 May 24.

Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD.

Purpose: Large interindividual variations in volume regression of non-small cell lung cancer (NSCLC) are observable on standard cone beam computed tomography (CBCT) during fractionated radiation therapy. Here, a method for automated assessment of tumor volume regression is presented and its potential use in response adapted personalized radiation therapy is evaluated empirically.

Methods And Materials: Automated deformable registration with calculation of the Jacobian determinant was applied to serial CBCT scans in a series of 99 patients with NSCLC. Tumor volume at the end of treatment was estimated on the basis of the first one third and two thirds of the scans. The concordance between estimated and actual relative volume at the end of radiation therapy was quantified by Pearson's correlation coefficient. On the basis of the estimated relative volume, the patients were stratified into 2 groups having volume regressions below or above the population median value. Kaplan-Meier plots of locoregional disease-free rate and overall survival in the 2 groups were used to evaluate the predictive value of tumor regression during treatment. Cox proportional hazards model was used to adjust for other clinical characteristics.

Results: Automatic measurement of the tumor regression from standard CBCT images was feasible. Pearson's correlation coefficient between manual and automatic measurement was 0.86 in a sample of 9 patients. Most patients experienced tumor volume regression, and this could be quantified early into the treatment course. Interestingly, patients with pronounced volume regression had worse locoregional tumor control and overall survival. This was significant on patient with non-adenocarcinoma histology.

Conclusions: Evaluation of routinely acquired CBCT images during radiation therapy provides biological information on the specific tumor. This could potentially form the basis for personalized response adaptive therapy.
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http://dx.doi.org/10.1016/j.ijrobp.2014.03.038DOI Listing
July 2014

Pattern of loco-regional failure after definitive radiotherapy for non-small cell lung cancer.

Acta Oncol 2014 Mar 26;53(3):336-41. Epub 2013 Dec 26.

Department of Oncology, Odense University Hospital , Odense , Denmark.

Unlabelled: Non-small cell lung cancer (NSCLC) is associated with poor survival even though patients are treated with curatively intended radiotherapy. Survival is affected negatively by lack of loco-regional tumour control, but survival is also influenced by comorbidity caused by age and smoking, and occurrence of distant metastasis. It is challenging to evaluate loco-regional control after definitive radiotherapy for NSCLC since it is difficult to distinguish between radiation-induced damage to the lung tissue and tumour progression/recurrence. In addition it may be useful to distinguish between intrapulmonary failure and mediastinal failure to be able to optimize radiotherapy in order to improve loco-regional control even though it is not easy to discriminate between the two sites of failure.

Material And Methods: This study is a retrospective analysis of 331 NSCLC patients treated with definitive radiotherapy from 2002 to 2011. The patients were treated consecutively at the Department of Oncology, Odense University Hospital, Denmark with at least 60 Gy. All patients were followed in a planned follow-up schedule and no patients were lost for follow-up.

Results: At the time of the analysis 93 patients had loco-regional failure only. Of these patients, 68 had intrapulmonary failure only, one patient had failure in mediastinum only, and 24 patients had intrapulmonary failure as well as mediastinal failure. Of the patients which had lung failure only, 78% had mediastinal involvement at treatment start. The only covariate with significant impact on developing intrapulmonary failure only was gross tumour volume. Median survival for the total group of 331 patients was 19 months. The median survival for patients with intrapulmonary failure only was 19 months, and it was 20 months for the patients with mediastinal relapse.

Conclusion: We conclude that focus should be on increasing doses to intrapulmonary tumour volume, when dose escalation is applied to improve local tumour control in NSCLC patients treated with definitive radiotherapy, since most recurrences are located here.
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http://dx.doi.org/10.3109/0284186X.2013.868035DOI Listing
March 2014

Time evolution of regional CT density changes in normal lung after IMRT for NSCLC.

Radiother Oncol 2013 Oct 20;109(1):89-94. Epub 2013 Sep 20.

Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Laboratory of Radiation Physics, Odense University Hospital, Denmark. Electronic address:

Purpose: This study investigates the clinical radiobiology of radiation induced lung disease in terms of regional computed tomography (CT) density changes following intensity modulated radiotherapy (IMRT) for non-small-cell lung cancer (NSCLC).

Methods: A total of 387 follow-up CT scans in 131 NSCLC patients receiving IMRT to a prescribed dose of 60 or 66 Gy in 2 Gy fractions were analyzed. The dose-dependent temporal evolution of the density change was analyzed using a two-component model, a superposition of an early, transient component and a late, persistent component.

Results: The CT density of healthy lung tissue was observed to increase significantly (p<0.0001) for all dose levels after IMRT. The time evolution and the size of the density signal depend on the local delivered dose. The transient component of the density signal was found to peak in the range of 3-4 months, while the density tends to stabilize at times >12 months.

Conclusions: The radiobiology of lung injury may be analyzed in terms of CT density change. The initial transient change in density is consistent with radiation pneumonitis, while the subsequent stabilization of the density is consistent with pulmonary fibrosis.
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http://dx.doi.org/10.1016/j.radonc.2013.08.041DOI Listing
October 2013

Four-dimensional dose evaluation of inhomogeneous dose distributions planned for non-small cell lung cancer patients with lymph node involvement.

Acta Oncol 2014 May 12;53(5):707-12. Epub 2013 Sep 12.

Laboratory of Radiation Physics, Odense University Hospital , Odense , Denmark.

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http://dx.doi.org/10.3109/0284186X.2013.835492DOI Listing
May 2014

Stereotactic body radiation therapy versus conventional radiation therapy in patients with early stage non-small cell lung cancer: an updated retrospective study on local failure and survival rates.

Acta Oncol 2013 Oct 1;52(7):1552-8. Epub 2013 Aug 1.

Department of Oncology, Odense University Hospital , Denmark.

Introduction: Stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) is now an accepted and patient friendly treatment, but still controversy exists about its comparability to conventional radiation therapy (RT). The purpose of this single-institutional report is to describe survival outcome for medically inoperable patients with early stage NSCLC treated with SBRT compared with high dose conventional RT.

Material And Methods: From August 2005 to June 2012, 100 medically inoperable patients were treated with SBRT at Odense University Hospital. The thoracic RT consisted of 3 fractions (F) of 15-22 Gy delivered in nine days. For comparison a group of 32 medically inoperable patients treated with conventional RT with 80 Gy/35-40 F (5 F/week) in the period of July 1998 to August 2011 were analyzed. All tumors had histological or cytological proven NSCLC T1-2N0M0.

Results: The median overall survival was 36.1 months versus 24.4 months for SBRT and conventional RT, respectively (p = 0.015). Local failure-free survival rates at one year were in SBRT group 93% versus 89% in the conventional RT group and at five years 69% versus 66%, SBRT and conventional RT respectively (p = 0.99). On multivariate analysis, female gender and performance status of 0-1 and SBRT predicted improved prognosis.

Conclusion: In a cohort of patients with NSCLC there was a significant difference in overall survival favoring SBRT. Performance status of 0-1, female gender and SBRT predicted improved prognosis. However, staging procedure, confirmation procedure of recurrence and technical improvements of radiation treatment is likely to influence outcomes. However, SBRT seems to be as efficient as conventional RT and is a more convenient treatment for the patients.
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http://dx.doi.org/10.3109/0284186X.2013.813635DOI Listing
October 2013