| 1. |
- Benedek, Hunor, et al.
(författare)
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The effect of prostate motion during hypofractionated radiotherapy can be reduced by using flattening filter free beams
- 2018
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Ingår i: Physics and imaging in radiation oncology. - : Elsevier BV. - 2405-6316. ; 6, s. 66-70
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Hypofractionated radiotherapy of prostate cancer reduces the overall treatment time but increases the per-fraction beam-on time due to the higher fraction doses. This increased fraction treatment time results in a larger uncertainty of the prostate position. The purpose of this study was to investigate the effect of prostate motion during flattening filter free (FFF) Volumetric Modulated Arc Therapy (VMAT) in ultrahypofractionation of prostate cancer radiotherapy with preserved plan quality compared to conventional flattened beams.Materials and methods: Nine prostate patients from the Scandinavian HYPO-RT-PC trial were re-planned using VMAT technique with both conventional and flattening filter free beams. Two fractionation schedules were used, one hypofractionated (42.7 Gy in 7 fractions), and one conventional (78.0 Gy in 39 fractions). Pre-treatment verification measurements were performed on all plans and the treatment time was recorded. Measurements with simulated prostate motion were performed for the plans with the longest treatment times. Results: All the 10FFF plans fulfilled the clinical gamma pass rate, 90% (3%, 2 mm), during all simulated prostate motion trajectories. The 10MV plans only fulfilled the clinical pass rate for three of the trajectories. The mean beam-on-time for the hypofractionated plans were reduced from 2.3 min to 1.0 min when using 10FFF compared to 10MV. No clinically relevant differences in dose distribution were identified when comparing the plans with different beam qualities. Conclusion: Flattening-filter free VMAT reduces treatment times, limiting the dosimetric effect of organ motion for ultrahypofractionated prostate cancer with preserved plan quality.
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| 2. |
- Bonde, Tiago M., et al.
(författare)
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Risk of prostate cancer death after radical radiotherapy with neoadjuvant and adjuvant therapy with bicalutamide or gonadotropin-releasing hormone agonists
- 2023
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 62:12, s. 1815-1821
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Tidskriftsartikel (refereegranskat)abstract
- Background: Oncological outcome after radical radiotherapy (RRT) combined with neoadjuvant and adjuvant androgen suppression therapy (AST) may differ according to type of AST. The aim of this nationwide register-based study was to investigate risk of prostate cancer (Pca) death after different neoadjuvant and adjuvant ASTs; (i) bicalutamide, (ii) gonadotropin-releasing hormone agonists (GnRH) or (iii) combined bicalutamide and GnRH (CAB), together with RRT.Materials and MethodsData for 6882 men diagnosed with high-risk Pca between 2007 and 2020 and treated with primary RRT was retrieved from Prostate Cancer data Base Sweden (PCBaSe) 5.0. Time to Pca death according to type of neoadjuvant and adjuvant AST was assessed by use of Kaplan-Meier plots and Cox proportional hazard models adjusted for putative confounders.Results: Data were stratified by RRT type since the effect of AST in risk of Pca death differed according to type of RRT. Compared with the reference RRT combined with neoadjuvant CAB/adjuvant GnRH, risk of Pca death for men treated with CAB/bicalutamide and conventionally fractionated external beam radiotherapy (CF-EBRT) was hazard ratio (HR) 0.73 (95% CI: 0.50-1.04), hypofractionated EBRT (HF-EBRT), HR 1.35 (95% CI: 0.65-2.81) and EBRT with high dose rate brachytherapy (EBRT-HDRBT), HR 0.85 (95% CI: 0.37-1.95). Risk of Pca death for men treated with bicalutamide/bicalutamide and: (i) CF-EBRT was HR 2.35 (95% CI: 1.42-3.90), (ii) HF-EBRT, HR 0.70 (95% CI: 0.26-1.85), (iii) HF-EBRT, HR 4.07 (95% CI: 1.88-8.77) vs the reference.Conclusion: In this observational study, risk of Pca death between men receiving different combinations of AST varied according to RRT type. No difference was found in risk of Pca death for men treated with bicalutamide or GnRH as adjuvant therapy to RRT following neoadjuvant CAB. Risk of Pca death was increased for men with monotherapy neo-/adjuvant bicalutamide in combination with CF-EBRT or EBRT-HDRBT.
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| 3. |
- Bosco, Cecilia, et al.
(författare)
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Prostate Cancer Radiation Therapy and Risk of Thromboembolic Events
- 2017
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : ELSEVIER SCIENCE INC. - 0360-3016 .- 1879-355X. ; 97:5, s. 1026-1031
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the risk of thromboembolic disease (TED) after radiation therapy (RT) with curative intent for prostate cancer (PCa).Patients and Methods: We identified all men who received RT as curative treatment (n=9410) and grouped according to external beam RT (EBRT) or brachytherapy (BT). By comparing with an age-and county-matched comparison cohort of PCa-free men (n = 46,826), we investigated risk of TED after RT using Cox proportional hazard regression models. The model was adjusted for tumor characteristics, demographics, comorbidities, PCa treatments, and known risk factors of TED, such as recent surgery and disease progression.Results: Between 2006 and 2013, 6232 men with PCa received EBRT, and 3178 underwent BT. A statistically significant association was found between EBRT and BT and risk of pulmonary embolism in the crude analysis. However, upon adjusting for known TED risk factors these associations disappeared. No significant associations were found between BT or EBRT and deep venous thrombosis.Conclusion: Curative RT for prostate cancer using contemporary methodologies was not associated with an increased risk of TED.
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| 4. |
- Fransson, Per, et al.
(författare)
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Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC) : patient-reported quality-of-life outcomes of a randomised, controlled, non-inferiority, phase 3 trial
- 2021
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Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 22:2, s. 235-245
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The HYPO-RT-PC trial compared conventionally fractionated radiotherapy with ultra-hypofractionated radiotherapy in patients with localised prostate cancer. Ultra-hypofractionation was non-inferior to conventional fractionation regarding 5-year failure-free survival and toxicity. We aimed to assess whether patient-reported quality of life (QOL) differs between conventional fractionation and ultra-hypofractionation up to 6 years after treatment in the HYPO-RT-PC trial.METHODS: HYPO-RT-PC is a multicentre, open-label, randomised, controlled, non-inferiority, phase 3 trial done in 12 centres (seven university hospitals and five county hospitals) in Sweden and Denmark. Inclusion criteria were histologically verified intermediate-to-high-risk prostate cancer (defined as T1c-T3a with one or two of the following risk factors: stage T3a; Gleason score ≥7; and prostate-specific antigen 10-20 ng/mL with no evidence of lymph node involvement or distant metastases), age up to 75 years, and WHO performance status 0-2. Participants were randomly assigned (1:1) to conventional fractionation (78·0 Gy in 39 fractions, 5 days per week for 8 weeks) or ultra-hypofractionation (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) via a minimisation algorithm with stratification by trial centre, T-stage, Gleason score, and prostate-specific antigen. QOL was measured using the validated Prostate Cancer Symptom Scale (PCSS) and European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) at baseline, the end of radiotherapy, months 3, 6, 12, and 24 after radiotherapy, every other year thereafter up to 10 years, and at 15 years. The primary endpoint (failure-free survival) has been reported elsewhere. Here we report QOL, a secondary endpoint analysed in the per-protocol population, up to 6 years after radiotherapy. The HYPO-RT-PC trial is registered with the ISRCTN registry, ISRCTN45905321.FINDINGS: Between July 1, 2005, and Nov 4, 2015, 1200 patients were enrolled and 1180 were randomly assigned (conventional fractionation n=591, ultra-hypofractionation n=589); 1165 patients (conventional fractionation n=582, ultra-hypofractionation n=583) were included in this QOL analysis. 158 (71%) of 223 patients in the conventional fractionation group and 146 (66%) of 220 in the ultra-hypofractionation group completed questionnaires at 6 years. The median follow-up was 48 months (IQR 25-72). In seven of ten bowel symptoms or problems the proportion of patients with clinically relevant deteriorations at the end of radiotherapy was significantly higher in the ultra-hypofractionation group than in the conventional fractionation group (stool frequency [p<0·0001], rush to toilet [p=0·0013], flatulence [p=0·0013], bowel cramp [p<0·0001], mucus [p=0·0014], blood in stool [p<0·0001], and limitation in daily activity [p=0·0014]). There were no statistically significant differences in the proportions of patients with clinically relevant acute urinary symptoms or problems (total 14 items) and sexual functioning between the two treatment groups at end of radiotherapy. Thereafter, there were no clinically relevant differences in urinary, bowel, or sexual functioning between the groups. At the 6-year follow-up there was no difference in the incidence of clinically relevant deterioration between the groups for overall urinary bother (43 [33%] of 132 for conventional fractionation vs 33 [28%] of 120 for ultra-hypofractionation; mean difference 5·1% [95% CI -4·4 to 14·6]; p=0·38), overall bowel bother (43 [33%] of 129 vs 34 [28%] of 123; 5·7% [-3·8 to 15·2]; p=0·33), overall sexual bother (75 [60%] of 126 vs 59 [50%] of 117; 9·1% [-1·4 to 19·6]; p=0·15), or global health/QOL (56 [42%] of 134 vs 46 [37%] of 125; 5·0% [-5·0 to 15·0]; p=0·41).INTERPRETATION: Although acute toxicity was higher for ultra-hypofractionation than conventional fractionation, this long-term patient-reported QOL analysis shows that ultra-hypofractionation was as well tolerated as conventional fractionation up to 6 years after completion of treatment. These findings support the use of ultra-hypofractionation radiotherapy for intermediate-to-high-risk prostate cancer.
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| 5. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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A prospective phase II study of prostate-specific antigen-guided salvage radiotherapy and Ga-68-PSMA-PET for biochemical relapse after radical prostatectomy-The PROPER 1 trial
- 2022
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Ingår i: Clinical and Translational Radiation Oncology. - : Elsevier BV. - 2405-6308. ; 36, s. 77-82
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: The treatment of biochemical recurrence (BCR) after prostatectomy is challenging as the site of the recurrence is often undetectable. Our aim was to test a personalised treatment concept for BCR based on PSA kinetics during salvage radiotherapy (SRT) combined with prostate-specific membrane antigen positron emission tomography (PSMA-PET). Materials and methods: This phase II trial included 100 patients with BCR. PSMA-PET was performed at baseline. PSA was measured weekly during SRT. Initially, 70 Gy in 35 fractions was prescribed to the prostate bed. Radiotherapy was adapted after 50 Gy. Non-responders (PSA still >= 0.15 ng/mL) received sequential lymph node irradiation with a boost to PSMA-PET positive lesions, while responders (PSA < 0.15 ng/mL) continued SRT as planned. PET-findings were only taken into consideration for treatment planning in case of PSA non-response after 50 Gy. Results: Data from 97 patients were eligible for analysis. Thirty-four patients were classified as responders and 63 as non-responders. PSMA-PET was positive in 3 patients (9%) in the responder group and in 22 (35%) in the non-responder group (p = 0.007). The three-year failure-free survival was 94% for responders and 68% for non-responders (median follow-up 38 months). There were no significant differences in physician-reported urinary and bowel toxicity. Patient-reported diarrhoea at end of SRT was more common among non-responders. Conclusion: This new personalised treatment concept with intensified SRT based on PSA response demonstrated a high tumour control rate in both responders and non-responders. These results suggest a clinically significant effect with moderate side effects in a patient group with otherwise poor prognosis. PSMA-PET added limited value. The treatment approach is now being evaluated in a phase III trial.
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| 6. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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Change in prostate volume during extreme hypo-fractionation analysed with MRI
- 2014
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Ingår i: Radiation Oncology. - 1748-717X. ; 9, s. 22-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hypo-fractionated external beam radiotherapy with narrow CTV-PTV margins is increasingly applied for prostate cancer. This demands a precise target definition and knowledge on target location and extension during treatment. It is unclear how increase in fraction size affects changes in prostate volume during treatment. Our aim was to study prostate volume changes during extreme hypo-fractionation (7 x 6.1 Gy) by using sequential MRIs. Methods: Twenty patients treated with extreme hypo-fractionation were recruited from an on-going prospective randomized phase III trial. An MRI scan was done before start of treatment, at mid treatment and at the end of radiotherapy. The prostate was delineated at each MRI and the volume and maximum extension in left-right, anterior-posterior and cranial-caudal directions were measured. Results: There was a significant increase in mean prostate volume (14%) at mid treatment as compared to baseline. The prostate volume remained enlarged (9%) at the end of radiotherapy. Prostate swelling was most pronounced in the anterior-posterior and cranial-caudal directions. Conclusions: Extreme hypo-fractionation induced a significant prostate swelling during treatment that was still present at the time of last treatment fraction. Our results indicate that prostate swelling is an important factor to take into account when applying treatment margins during short extreme hypo-fractionation, and that tight margins should be applied with caution.
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| 7. |
- Gunnlaugsson, Adalsteinn
(författare)
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Chemoradiation in Gastrointestinal Cancer
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Locally advanced inextirpable gastrointestinal cancer has poor prognosis and is associated with high morbidity. One treatment option is to use radiotherapy, often combined with chemotherapy (chemoradiation), either as preoperative treatment to facilitate surgery or in the palliative setting to relieve symptoms. The aim of this thesis was to investigate efficacy and toxicity of intensive chemoradiation including conformal radiotherapy and newer chemotherapeutic agents. Oxaliplatin and capecitabine together with 50 Gy radiotherapy was used in a national phase I-II study (CORGI), divided in two parts by tumor location. Among 61 patients with locally advanced colorectal cancer, primary tumor or local recurrence, with or without distant metastases, the objective local response rate was 58% and 79% went to surgical resection (paper I) The main side-effect was diarrhea. 39 patients with pancreatic or biliary tract cancer were included (paper II). The maximum tolerated chemotherapy doses were determined. Dose-limiting toxicity was nausea/vomiting. The local response rate was 21 %. In both CORGI studies there was a high frequency of sustained local control at two years. The most important risk factor for diarrhea during chemoradiation was the volume of small bowel that received >15 Gy (paper III). Enteritis is thought to be mediated by eradication of intestinal crypts. In a mouse model we found that adding oxaliplatin and 5-FU to radiation increased the mucosal damage (paper IV). Thus, chemoradiation is effective and feasible in several types of gastrointestinal cancers. Sparing small bowel from radiation is important.
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| 8. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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Dose-volume relationships between enteritis and irradiated bowel volumes during 5-fluorouracil and oxaliplatin based chemoradiotherapy in locally advanced rectal cancer
- 2007
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 46:7, s. 937-944
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. Radiation enteritis is the main acute side-effect during pelvic irradiation. The aim of this study was to quantify the dose-volume relationship between irradiated bowel volumes and acute enteritis during combined chemoradiotherapy for rectal cancer. Material and methods. Twenty-eight patients with locally advanced rectal cancer received chemoradiotherapy. The radiation therapy was given with a traditional multi-field technique to a total dose of 50 Gy, with concurrent 5-Fluorouracil (5-FU) and oxaliplatin (OXA) based chemotherapy. All patients underwent three-dimensional CT-based treatment planning. Individual loops of small and large bowel as well as a volume defined as "whole abdomen'' were systematically contoured on each CT slice, and dose-volume histograms were generated. Diarrhea during treatment was scored retrospectively according to the NCI Common Toxicity Criteria scale. Results. There was a strong correlation between the occurrence of grade 2 + diarrhea and irradiated small bowel volume, most notably at doses > 15 Gy. Neither irradiated large bowel volume, nor irradiated "whole abdomen'' volume correlated significantly with diarrhea. Clinical or treatment related factors such as age, gender, hypertension, previous surgery, enterostomy, or dose fractionation (1.8 vs. 2.0 Gy/fraction) did not correlate with grade 2 + diarrhea. Discussion. This study indicates a strong dose-volume relationship between small bowel volume and radiation enteritis during 5-FU-OXA-based chemoradiotherapy. These findings support the application of maneuvers to minimize small bowel irradiation, such as using a "belly board'' or the use of IMRT technique aiming at keeping the small bowel volume receiving more than 15 Gy under 150 cc.
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| 9. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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Multicentre phase I-II trial of capecitabine and oxaliplatin in combination with radiotherapy for unresectable pancreatic and biliary tract cancer: The CORGI-U study
- 2010
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 1879-0887 .- 0167-8140. ; 95:3, s. 292-297
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: In this multicentre phase I-II trial we evaluated the feasibility and efficacy of capecitabine and oxaliplatin followed by the combination of these two drugs with radiotherapy in patients with locally advanced pancreatic or biliary tract cancer. Material and methods: Thirty-nine patients with inextirpable adenocarcinoma of the pancreas, gallbladder or extrahepatic bile ducts were included. Two cycles of XELOX (capecitabine 1000 mg/m(2) bid d1-14 + oxaliplatin 130 mg/m(2) d1, q3w) were followed by XELOX-RT (radiotherapy (50.4 Gy), combined with capecitabine 750-675 mg/m(2) bid every radiotherapy day and oxaliplatin 40-30 mg/m(2) once weekly). Primary end-points were tolerance (phase I) and objective response (phase II). Results: The maximum tolerated doses of oxaliplatin and capecitabine to combine with irradiation were 30 mg/m(2) and 675 mg/m(2), respectively. Twenty-one percent (95% CI: 9-38%) of evaluable patients achieved partial response. Five patients went through surgery (three R0 resections). Two-year survival was 28%, and estimated local tumour control rate at 2 years was 72%. The most common grade 3-4 toxicity was nausea and vomiting. Conclusions: XELOX-RT (30 mg/m(2) oxaliplatin/675 mg/m(2) capecitabine in combination with 50.4 Gy/28 fractions) was well tolerated and effective for locally advanced pancreatic and biliary tract cancer. (C) 2010 Published by Elsevier Ireland Ltd. Radiotherapy and Oncology 95 (2010) 292-297
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| 10. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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Multicentre phase II trial of capecitabine and oxaliplatin in combination with radiotherapy for unresectable colorectal cancer : The CORGI-L study
- 2009
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 45:5, s. 807-813
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: This study assessed radiotherapy combined with capecitabine and oxaliplatin in patients with primary, inextirpable colorectal adenocarcinoma. PATIENTS AND METHODS: Forty-nine patients entered the trial. Two cycles of XELOX (capecitabine 1000mg/m(2) bid d1-14+oxaliplatin 130mg/m(2) d1, q3w) were followed by radiotherapy (50.4Gy), combined with capecitabine 825mg/m(2) bid every radiotherapy day and oxaliplatin 60mg/m(2) once weekly. The primary end-point was objective response. RESULTS: Forty-seven patients were evaluable. Twenty-nine (62% [95% CI: 46-75%]) achieved complete or partial response. Thirty-eight (81%) went through surgery of whom 37 (97%) had an R0 resection and five (13%) had a pathological complete response. Seventy-eight percent were alive and estimated local progression rate was 11% at 2 years. The most common grade 3+ toxicity during chemoradiotherapy was diarrhoea (24%). CONCLUSIONS: XELOX-RT was feasible and showed promising efficacy when treating patients with primary inextirpable colorectal cancer, establishing high local control rate.
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| 11. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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PSA decay during salvage radiotherapy for prostate cancer as a predictor of disease outcome – 5 year follow-up of a prospective observational study
- 2020
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Ingår i: Clinical and Translational Radiation Oncology. - : Elsevier BV. - 2405-6308. ; 24, s. 23-28
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Biochemical recurrence after prostatectomy is commonly treated with salvage radiotherapy (SRT). In this prospective observational study we investigated the PSA decay rate, determined by predefined serial PSA measurements during SRT, as a predictor for treatment outcome.Materials and methods: Between 2013 and 2016, 214 patients were included in the study. The prescribed dose to the prostate bed was 70 Gy in 35 fractions (7 weeks) without hormonal treatment. PSA was measured weekly during SRT. Assuming first order kinetics, a PSA decay-rate constant (k) was calculated for 196 eligible patients. The ability of k to predict disease progression was compared with known clinical prediction parameters using Cox regression, logistic regression and ROC analyses. Disease progression was defined as continuously rising PSA after SRT, PSA increase by ≥0.2 ng/ml above nadir after SRT, hormonal treatment or clinical progression.Results: After a median follow up of 4.7 years the estimated failure-free survival at 5 years was 56%. The PSA decay-rate constant (k) was found to be the strongest predictor of disease progression in both uni-and multivariable analyses.Conclusion: The addition of k to established clinical variables significantly improves the possibility to predict treatment outcome after SRT and could be used to personalize future therapies.
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| 12. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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Target definition in radiotherapy of prostate cancer using magnetic resonance imaging only workflow
- 2019
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Ingår i: Physics and imaging in radiation oncology. - : Elsevier BV. - 2405-6316. ; 9, s. 89-91
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Tidskriftsartikel (refereegranskat)abstract
- In magnetic resonance (MR) only radiotherapy, the target delineation needs to be performed without computed tomography (CT). We investigated in thirteenpatients with prostate cancer, how the clinical target volume (CTV) was affected, when the target delineation procedure was changed from using both CT and MRimages to using MR images only. The mean volume of the CTVCT/MR was 61.0 cm3 as compared to 49.9 cm3 from MR-only based target delineation, corresponding toan average decrease of 18%. Our results show that CTVMR-only was consistently smaller than CTVCT/MR, which has to be taken into consideration before clinicalcommissioning of MR-only radiotherapy.
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| 13. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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The effect on the small bowel of 5-FU and oxaliplatin in combination with radiation using a microcolony survival assay
- 2009
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Ingår i: Radiation Oncology. - London : BioMed Central. - 1748-717X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Background: In locally advanced rectal cancer, 5-Fluorouracil (5-FU)-based chemoradiation is the standard treatment. The main acute toxicity of this treatment is enteritis. Due to its potential radiosensitizing properties, oxaliplatin has recently been incorporated in many clinical chemoradiation protocols. The aim of this study was to investigate to what extent 5-FU and oxaliplatin influence the radiation (RT) induced small bowel mucosal damage when given in conjunction with single or split dose RT.Methods: Immune competent balb-c mice were treated with varying doses of 5-FU, oxaliplatin (given intraperitoneally) and total body RT, alone or in different combinations in a series of experiments. The small bowel damage was studied by a microcolony survival assay. The treatment effect was evaluated using the inverse of the slope (D(0)) of the exponential part of the dose-response curve.Results: In two separate experiments the dose-response relations were determined for single doses of RT alone, yielding D(0) values of 2.79 Gy (95% CI: 2.65 - 2.95) and 2.98 Gy (2.66 - 3.39), for doses in the intervals of 5-17 Gy and 5-10 Gy, respectively. Equitoxic low doses (IC5) of the two drugs in combination with RT caused a decrease in jejunal crypt count with significantly lower D(0): 2.30 Gy (2.10 - 2.56) for RT+5-FU and 2.27 Gy (2.08 - 2.49) for RT+oxaliplatin. Adding both drugs to RT did not further decrease D(0):2.28 Gy (1.97 - 2.71) for RT+5-FU+oxaliplatin. A clearly higher crypt survival was noted for split course radiation (3 x 2.5 Gy) compared to a single fraction of 7.5 Gy. The same difference was seen when 5-FU and/or oxaliplatin were added.Conclusion: Combining 5-FU or oxaliplatin with RT lead to an increase in mucosal damage as compared to RT alone in our experimental setting. No additional reduction of jejunal crypt counts was noted when both drugs were combined with single dose RT. The higher crypt survival with split dose radiation indicates a substantial recovery between radiation fractions. This mucosalsparing effect achieved by fractionation was maintained also when chemotherapy was added.
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| 14. |
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| 15. |
- Gustafsson, Christian, et al.
(författare)
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Registration free automatic identification of gold fiducial markers in MRI target delineation images for prostate radiotherapy
- 2017
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Ingår i: Medical physics (Lancaster). - : Wiley. - 0094-2405. ; 44:11, s. 5563-5574
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The superior soft tissue contrast of magnetic resonance imaging (MRI) compared to computed tomography (CT) has urged the integration of MRI and elimination of CT in radiotherapy treatment (RT) for prostate. An intraprostatic gold fiducial marker (GFM) appears hyperintense on CT. On T2-weighted (T2w) MRI target delineation images, the GFM appear as a small signal void similar to calcifications and post biopsy fibrosis. It can therefore be difficult to identify the markers without CT. Detectability of GFMs can be improved using additional MR images, which are manually registered to target delineation images. This task requires manual labor, and is associated with interoperator differences and image registration errors. The aim of this work was to develop and evaluate an automatic method for identification of GFMs directly in the target delineation images without the need for image registration.Methods: T2w images, intended for target delineation, and multiecho gradient echo (MEGRE) images intended for GFM identification, were acquired for prostate cancer patients. Signal voids in the target delineation images were identified as GFM candidates. The GFM appeared as round, symmetric, signal void with increasing area for increasing echo time in the MEGRE images. These image features were exploited for automatic identification of GFMs in a MATLAB model using a patient training dataset (n = 20). The model was validated on an independent patient dataset (n = 40). The distances between the identified GFM in the target delineation images and the GFM in CT images were measured. A human observatory study was conducted to validate the use of MEGRE images.Results: The sensitivity, specificity, and accuracy of the automatic method and the observatory study was 84%, 74%, 81% and 98%, 94%, 97%, respectively. The mean absolute difference in the GFM distances for the automatic method and observatory study was 1.28 1.25 mm and 1.14 +/- 1.06 mm, respectively.Conclusions: Multiecho gradient echo images were shown to be a feasible and reliable way to perform GFM identification. For clinical practice, visual inspection of the results from the automatic method is needed at the current stage.
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| 16. |
- Gustafsson, Christian, et al.
(författare)
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Using C-Arm X-ray images from marker insertion to confirm the gold fiducial marker identification in an MRI-only prostate radiotherapy workflow
- 2018
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Ingår i: Journal of Applied Clinical Medical Physics. - : Wiley. - 1526-9914. ; 19:6, s. 185-192
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer radiotherapy workflows, solely based on magnetic resonance imaging (MRI), are now in clinical use. In these workflows, intraprostatic gold fiducial markers (GFM) show similar signal behavior as calcifications and bleeding in T2-weighted MRI-images. Accurate GFM identification in MRI-only radiotherapy workflows is therefore a major challenge. C-arm X-ray images (CkV-images), acquired at GFM implantation, could provide GFM position information and be used to confirm correct identification in T2-weighted MRI-images. This would require negligible GFM migration between implantation and MRI-imaging. Marker migration was therefore investigated. The aim of this study was to show the feasibility of using CkV-images to confirm GFM identification in an MRI-only prostate radiotherapy workflow. An anterior-posterior digitally reconstructed radiograph (DRR)-image and a mirrored posterior-anterior CkV-image were acquired two weeks apart for 16 patients in an MRI-only radiotherapy workflow. The DRR-image originated from synthetic CT-images (created from MRI-images). A common image geometry was defined between the DRR- and CkV-image for each patient. A rigid registration between the GFM center of mass (CoM) coordinates was performed and the distance between each of the GFM in the DRR- and registered CkV-image was calculated. The same methodology was used to assess GFM migration for 31 patients in a CT-based radiotherapy workflow. The distance calculated was considered a measure of GFM migration. A statistical test was performed to assess any difference between the cohorts. The mean absolute distance difference for the GFM CoM between the DRR- and CkV-image in the MRI-only cohort was 1.7 ± 1.4 mm. The mean GFM migration was 1.2 ± 0.7 mm. No significant difference between the measured total distances of the two cohorts could be detected (P = 0.37). This demonstrated that, a C-Arm X-ray image acquired from the GFM implantation procedure could be used to confirm GFM identification from MRI-images. GFM migration was present but did not constitute a problem.
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| 17. |
- Haraldsdottir, Sigurdis, et al.
(författare)
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Krabbamein í ristli og endaþarmi - yfirlitsgrein
- 2014
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Ingår i: Laeknabladid. - 0023-7213. ; 100:2, s. 75-82
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Forskningsöversikt (refereegranskat)abstract
- Colorectal cancer is the third most common cancer in the Western hemisphere and the incidence increases with increasing age. Most colorectal cancers are localized with or without lymph node metastases. Up to 20% of patients present with metastatic disease, most commonly to the liver. Surgery is the only curative therapy for localized colorectal cancer and adjuvant chemotherapy is usually recommended for patients with lymph node metastases. Surgery, radiation therapy and chemotherapy are the key components of rectal cancer therapy. Selected patients with recurrent and metastatic disease can be salvaged with surgery but chemotherapy remains the mainstay of therapy for advanced colorectal cancer. Substantial progress has been observed in the treatment of metastatic colorectal cancer in recent years.
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| 18. |
- Jóhannesson, Vilberg, et al.
(författare)
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Adaptive sequential plan-on-plan optimization during prostate-specific antigen response guided radiotherapy of recurrent prostate cancer
- 2021
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Ingår i: Physics and imaging in radiation oncology. - : Elsevier BV. - 2405-6316. ; 18, s. 5-10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Treatment adaptation based on tumour biomarker response during radiotherapy of prostate cancer, could be used for both escalation and de-escalation of radiation doses and volumes. To execute an adaptation involving extension of treatment volumes during radiation can however be restricted by the doses already delivered. The aim of this work was to develop a treatment planning method that addresses this challenge. Material and methods: A volumetric-modulated-arc-therapy (VMAT) planning method with sequential plan-on-plan optimization was developed for a prospective phase II trial including 100 patients on salvage radiotherapy (SRT) for prostate cancer recurrence. A treatment adaptation was performed after five weeks of SRT based on prostate-specific antigen response during this phase of the treatment. This involved extension of treatment volumes for non-responders (n = 64) to include pelvic lymph nodes and boost to 68Gallium-Prostate-Specific-Membrane-Antigen-Positron-Emission-Tomography positive lesions. This method was evolved by introducing an EQD2 (equivalent dose in 2.0 Gy fractions) correction of the base plan for improved dose coverage. Results: All dose-volume criteria for target coverage were met for the non-responders when based on physical dose. An EQD2 correction of the base plan for non-responders, implemented for the final 29 patients, led to a statistically significant improvement in dose coverage as compared to the 35 patients treated without EQD2 correction. Conclusions: This is to our knowledge the only study presented on biomarker-guided sequential VMAT radiotherapy using a plan-on-plan technique in the pelvis. By using a biologically adapted technique an improved target coverage was achieved without compromising doses to organs at risk.
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| 19. |
- Jóhannesson, Vilberg, et al.
(författare)
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Dose-volume relationships of planned versus estimated delivered radiation doses to pelvic organs at risk and side effects in patients treated with salvage radiotherapy for recurrent prostate cancer
- 2024
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Ingår i: Technical Innovations and Patient Support in Radiation Oncology. - 2405-6324. ; 29
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate estimated delivered dose distributions using weekly cone-beam computed tomography (CBCT) scans for pelvic organs at risk (OARs) in salvage radiotherapy (SRT) after radical prostatectomy. Furthermore, to compare them with the originally planned dose distributions and analyse associations with gastrointestinal (GI) and genitourinary (GU) side effects.METHODS: This study is part of a phase II trial involving SRT for recurrent prostate cancer. Treatment was personalised based on PSA response during SRT, classifying patients as PSA responders or non-responders. Estimated radiation dose distributions were obtained using deformable image registration from weekly CBCT scans. GI and GU toxicities were assessed using the RTOG toxicity scale, while patient-reported symptoms were monitored through self-assessment questionnaires.RESULTS: The study included 100 patients, with similar treatment-related side effects observed in both responders and non-responders. Differences in dose-volume metrics between the planned and estimated delivered doses for the examined OARs were mostly modest, although generally statistically significant. We identified statistically significant associations between QUANTEC-recommended dose-volume constraints and acute bowel toxicity, as well as late urinary patient-reported symptoms, for both the estimated delivered and planned dose distributions.CONCLUSION: We found small but statistically significant differences between estimated delivered and planned doses to OARs. These differences showed trends toward improved associations for estimated delivered dose distributions with side effects. Enhanced registration methods and imaging techniques could potentially further enhance the assessment of truly delivered doses and yield more reliable dose-volume constraints for future therapies.
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| 20. |
- Johnsson, Anders, et al.
(författare)
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Determinants for local tumour control probability after radiotherapy of anal cancer
- 2018
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140. ; 128:2, s. 380-386
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Anal squamous cell carcinoma is primarily treated with radiotherapy (RT), but the optimal RT dose for anal tumours of different sizes is not known. The purpose of this study was to identify determinants for local tumour control probability (LTCP). Material and methods: From a large Nordic database 901 patients who received RT for anal cancer between 2000 and 2007 were selected. LTCP was analysed in a series of uni- and multivariable regression analyses. Results: Higher RT dose, female gender and addition of chemotherapy were associated with higher LTCP whereas increasing tumour size, tumour invasiveness (stage T4) and lymph node metastases (N+) were associated with lower LTCP. Male patients needed approximately 10 Gy higher RT dose than female patients for similar LTCP. The addition of chemotherapy corresponded to 5–10 Gy RT dose. Conclusions: Our results basically support current guidelines recommending: (1) lower RT dose in small tumours (<4 cm), (2) higher RT dose larger tumours and in stages T4 and /or N+, (3) Chemo should be used in combination with RT. These results will hopefully constitute the basis for future trials, aiming at individualized RT dosing in patients with anal cancer.
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| 21. |
- Koivula, Lauri, et al.
(författare)
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Intensity-based dual model method for generation of synthetic CT images from standard T2-weighted MR images - Generalized technique for four different MR scanners
- 2017
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140. ; 125:3, s. 411-419
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Recent studies have shown that it is possible to conduct entire radiotherapy treatment planning (RTP) workflow using only MR images. This study aims to develop a generalized intensity-based method to generate synthetic CT (sCT) images from standard T2-weighted (T2w) MR images of the pelvis. Materials and methods: This study developed a generalized dual model HU conversion method to convert standard T2w MR image intensity values to synthetic HU values, separately inside and outside of atlas-segmented bone volume contour. The method was developed and evaluated with 20 and 35 prostate cancer patients, respectively. MR images with scanning sequences in clinical use were acquired with four different MR scanners of three vendors. Results: For the generated synthetic CT (sCT) images of the 35 prostate patients, the mean (and maximal) HU differences in soft and bony tissue volumes were 16±6HUs (34HUs) and -46±56HUs (181HUs), respectively, against the true CT images. The average of the PTV mean dose difference in sCTs compared to those in true CTs was -0.6±0.4% (-1.3%). Conclusions: The study provides a generalized method for sCT creation from standard T2w images of the pelvis. The method produced clinically acceptable dose calculation results for all the included scanners and MR sequences.
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| 22. |
- Leon, Otilia, et al.
(författare)
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Phase I study of cetuximab in combination with 5-fluorouracil, mitomycin C and radiotherapy in patients with locally advanced anal cancer
- 2015
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 51:18, s. 2740-2746
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Tidskriftsartikel (refereegranskat)abstract
- Background: 5-fluorouracil (5FU) and mitomycin C (MMC)-based chemoradiotherapy (CRT) is standard treatment for anal squamous cell carcinoma. In this phase I study cetuximab was added and the primary aim was to determine the maximum tolerated dose (MTD) of 5FU and MMC in this combination. Methods and materials: Patients with locally advanced anal cancer, T2 (> 4 cm) -4N0-3M0, received weekly standard doses of cetuximab starting 1 week before CRT. Intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB) was given to 57.5/54.0/48.6 Gy in 27 fractions to primary tumour/lymph node metastases/adjuvant lymph node regions. 5FU/MMC was given concomitantly on RT weeks 1 and 5 according to a predefined dose escalation schedule. Results: Thirteen patients were enrolled. Two patients discontinued cetuximab due to hypersensitivity reaction. The median age was 65 years (range 46-70), nine were females, and 85% had stage IIIB disease. Dose-limiting toxicity events (diarrheoa, febrile neutropenia and thrombocytopenia) occurred in 3 of 11 patients. The most common grade 3-4 side-effects were radiation dermatitis (63%), haematologic toxicity (54%), and diarrheoa (36%). No treatment-related deaths occurred. Three months following completion of treatment, ten patients (91%) had a local complete remission (CR), but two patients had developed liver metastases, yielding a total CR rate of 73%. Conclusion: The MTDs were determined as 5FU 800 mg/m(2) on RT days 1-4 and 29-32 and MMC 8 mg/m(2) on days 1 and 29 when combined with IMRT/VMAT with SIB and cetuximab in locally advanced anal cancer.
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| 23. |
- Mannerberg, Annika, et al.
(författare)
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Dosimetric effects of adaptive prostate cancer radiotherapy in an MR-linac workflow
- 2020
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Ingår i: Radiation oncology (London, England). - : Springer Science and Business Media LLC. - 1748-717X. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The purpose was to evaluate the dosimetric effects in prostate cancer treatment caused by anatomical changes occurring during the time frame of adaptive replanning in a magnetic resonance linear accelerator (MR-linac) workflow. METHODS: Two MR images (MR1 and MR2) were acquired with 30 min apart for each of the 35 patients enrolled in this study. The clinical target volume (CTV) and organs at risk (OARs) were delineated based on MR1. Using a synthetic CT (sCT), ultra-hypofractionated VMAT treatment plans were created for MR1, with three different planning target volume (PTV) margins of 7 mm, 5 mm and 3 mm. The three treatment plans of MR1, were recalculated onto MR2 using its corresponding sCT. The dose distribution of MR2 represented delivered dose to the patient after 30 min of adaptive replanning, omitting motion correction before beam on. MR2 was registered to MR1, using deformable registration. Using the inverse deformation, the structures of MR1 was deformed to fit MR2 and anatomical changes were quantified. For dose distribution comparison the dose distribution of MR2 was warped to the geometry MR1. RESULTS: The mean center of mass vector offset for the CTV was 1.92 mm [0.13 - 9.79 mm]. Bladder volume increase ranged from 12.4 to 133.0% and rectum volume difference varied between -10.9 and 38.8%. Using the conventional 7 mm planning target volume (PTV) margin the dose reduction to the CTV was 1.1%. Corresponding values for 5 mm and 3 mm PTV margin were 2.0% and 4.2% respectively. The dose to the PTV and OARs also decreased from D1 to D2, for all PTV margins evaluated. Statistically significant difference was found for CTV Dmin between D1 and D2 for the 3 mm PTV margin (p < 0.01). CONCLUSIONS: A target underdosage caused by anatomical changes occurring during the reported time frame for adaptive replanning MR-linac workflows was found. Volume changes in both bladder and rectum caused large prostate displacements. This indicates the importance of thorough position verification before treatment delivery and that the workflow needs to speed up before introducing margin reduction.
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| 24. |
- Mannerberg, Annika, et al.
(författare)
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Faster and more accurate patient positioning with surface guided radiotherapy for ultra-hypofractionated prostate cancer patients
- 2021
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Ingår i: Technical Innovations and Patient Support in Radiation Oncology. - : Elsevier BV. - 2405-6324. ; 19, s. 41-45
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The aim of this study was to evaluate if surface guided radiotherapy (SGRT) can decrease patient positioning time for localized prostate cancer patients compared to the conventional 3-point localization setup method. The patient setup accuracy was also compared between the two setup methods. Materials and methods: A total of 40 localized prostate cancer patients were enrolled in this study, where 20 patients were positioned with surface imaging (SI) and 20 patients were positioned with 3-point localization. The setup time was obtained from the system log files of the linear accelerator and compared between the two methods. The patient setup was verified with daily orthogonal kV images which were matched based on the implanted gold fiducial markers. Resulting setup deviations between planned and online positions were compared between SI and 3-point localization. Results: Median setup time was 2:50 min and 3:28 min for SI and 3-point localization, respectively (p < 0.001). The median vector offset was 4.7 mm (range: 0–10.4 mm) for SI and 5.2 mm for 3-point localization (range: 0.41–17.3 mm) (p = 0.01). Median setup deviation in the individual translations for SI and 3-point localization respectively was: 1.1 mm and 1.9 mm in lateral direction (p = 0.02), 1.8 and 1.6 mm in the longitudinal direction (p = 0.41) and 2.2 mm and 2.6 mm in the vertical direction (p = 0.04). Conclusions: Using SGRT for positioning of prostate cancer patients provided a faster and more accurate patient positioning compared to the conventional 3-point localization setup.
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| 25. |
- Nilsson, Martin P., et al.
(författare)
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Patterns of recurrence in anal cancer : A detailed analysis
- 2020
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Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Anal cancer is a rare disease, which might be the reason for the "one size fits all" approach still used for radiotherapy target contouring. To refine and individualize future guidelines, detailed and contemporary pattern of recurrence studies are needed. Methods: Consecutive anal cancer patients, all treated with curative intent intensity-modulated radiotherapy (IMRT), were retrospectively studied (n = 170). Data was extracted from medical records and radiological images. Radiotherapy planning CT's and treatment plans were reviewed, and recurrences were mapped and categorized according to radiation dose. Results: The mean dose to the primary tumor was 59.0 Gy. With a median follow-up of 50 months (range 14-117 months), 5-year anal cancer specific survival was 86.1%. Only 1 of 20 local recurrences was located outside the high dose (CTVT) volume. More patients experienced a distant recurrence (n = 34; 20.0%) than a locoregional recurrence (n = 24; 14.1%). Seven patients (4.2%) had a common iliac and/or para-aortic (CI/PA) recurrence. External iliac lymph node involvement (P = 0.04), and metastases in ≥3 inguinal or pelvic lymph node regions (P = 0.02) were associated with a 15-18% risk of CI/PA recurrence. Following chemoradiotherapy, 6 patients with recurrent or primary metastatic CI/PA lymph nodes were free of recurrence at last follow-up. The overall rate of ano-inguinal lymphatic drainage (AILD) recurrence was 2 of 170 (1.2%), and among patients with inguinal metastases at initial diagnosis it was 2 of 65 (3.1%). Conclusions: We conclude that other measures than increased margins around the primary tumor are needed to improve local control. Furthermore, metastatic CI/PA lymph nodes, either at initial diagnosis or in the recurrent setting, should be considered potentially curable. Patients with certain patterns of metastatic pelvic lymph nodes might be at an increased risk of harboring tumor cells also in the CI/PA lymph nodes.
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