Hanne Tøndel1, Jo-Åsmund Lund2, Stian Lydersen3, Anne D Wanderås4, Bjørg Aksnessæther5, Christer Andre Jensen5, Stein Kaasa6, Arne Solberg7. 1. Cancer Clinic, St. Olavs Hospital, Trondheim University Hospital, Norway; Department of Cancer Research and Molecular Medicine, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology Trondheim, Norway. Electronic address: hanne.tondel@ntnu.no. 2. Department of Cancer Research and Molecular Medicine, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology Trondheim, Norway; Helse Møre and Romsdal, Ålesund, Norway. 3. Regional Centre for Child and Youth Mental Health and Child Welfare, Department of Mental Health, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology, Trondheim, Norway. 4. Cancer Clinic, St. Olavs Hospital, Trondheim University Hospital, Norway. 5. Helse Møre and Romsdal, Ålesund, Norway. 6. Department of Cancer Research and Molecular Medicine, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology Trondheim, Norway; Department of Oncology, Oslo University Hospital and University of Oslo, Norway; European Palliative Care Research Centre (PRC), Department of Cancer Research and Molecular Medicine, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology and St. Olavs Hospital, Trondheim University Hospital, Norway. 7. Cancer Clinic, St. Olavs Hospital, Trondheim University Hospital, Norway; Department of Cancer Research and Molecular Medicine, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology Trondheim, Norway.
Abstract
BACKGROUND: Novel cancer drugs are subject to strict scientific evaluation of safety and efficacy and usually undergo a cost effectiveness analysis before approval for use in clinical practice. For new techniques in radiotherapy (RT) such as image-guided radiotherapy (IGRT), this is often not the case. We performed a randomized controlled trial to compare daily cone beam computer tomography (CBCT) IGRT withreduced planning target volume (PTV) margins vs weekly orthogonal portal imaging with conventional PTV margins. The primary aim of the study was to investigate the effect of two different image guidance techniques on patient reported outcome (PRO) using early side effects as proxy outcome of late rectal side effects in patients receiving curative RT for prostate cancer. METHODS: This open label, phase 3 trial conducted at two RT centers in Norway enrolled men aged 18 years or older with previously untreated histologically proven intermediate or high-risk adenocarcinoma of the prostate. Patients eligible for radical RT received it after 3 months of total androgen blockage and were randomly assigned to 78 Gy in 39 fractions guided either by weekly offline orthogonal portal imaging (15 mm margins to PTV) or by daily online CBCT IGRT (7 mm margins to PTV). Based on previous results indicating that acute rectal side effects are a valid proxy outcome for late rectal side effects, the primary outcome was acute rectal toxicity at end of RT as evaluated by rectal bother scale (five of the items from PRO's QUFW94). The RIC-trial is registered with ClinicalTrials.gov, number NCT01550237. FINDINGS:Between October 2012 and June 2015, 257 patients were randomly assigned to weekly offline portal imaging (n = 129) or daily online CBCT IGRT (n = 128). Out of 250 evaluable patients, 96% completed PROs at baseline and 97% at end of RT. Baseline analyses demonstrated balance between groups for baseline characteristics as well as for PROs. In general, patients reported a small degree of side effects at end of RT, and there was no difference between groups for primary outcome (rectal bother scale of QUFW94 1.871 vs 1.884, p = 0.804). In addition, there were no significant differences between groups for any other gastrointestinal or urinary symptom as reported by QUFW94. Health related quality of life analyses (EORTC QLQ 30) demonstrated no differences between groups. INTERPRETATION: In radical RT for prostate cancer, daily CBCT IGRT with reduced PTV margins demonstrated no advantage with respect to patient reported side effects at end of RT as compared to weekly orthogonal offline portal imaging with standard PTV margins.
RCT Entities:
BACKGROUND: Novel cancer drugs are subject to strict scientific evaluation of safety and efficacy and usually undergo a cost effectiveness analysis before approval for use in clinical practice. For new techniques in radiotherapy (RT) such as image-guided radiotherapy (IGRT), this is often not the case. We performed a randomized controlled trial to compare daily cone beam computer tomography (CBCT) IGRT with reduced planning target volume (PTV) margins vs weekly orthogonal portal imaging with conventional PTV margins. The primary aim of the study was to investigate the effect of two different image guidance techniques on patient reported outcome (PRO) using early side effects as proxy outcome of late rectal side effects in patients receiving curative RT for prostate cancer. METHODS: This open label, phase 3 trial conducted at two RT centers in Norway enrolled men aged 18 years or older with previously untreated histologically proven intermediate or high-risk adenocarcinoma of the prostate. Patients eligible for radical RT received it after 3 months of total androgen blockage and were randomly assigned to 78 Gy in 39 fractions guided either by weekly offline orthogonal portal imaging (15 mm margins to PTV) or by daily online CBCT IGRT (7 mm margins to PTV). Based on previous results indicating that acute rectal side effects are a valid proxy outcome for late rectal side effects, the primary outcome was acute rectal toxicity at end of RT as evaluated by rectal bother scale (five of the items from PRO's QUFW94). The RIC-trial is registered with ClinicalTrials.gov, number NCT01550237. FINDINGS: Between October 2012 and June 2015, 257 patients were randomly assigned to weekly offline portal imaging (n = 129) or daily online CBCT IGRT (n = 128). Out of 250 evaluable patients, 96% completed PROs at baseline and 97% at end of RT. Baseline analyses demonstrated balance between groups for baseline characteristics as well as for PROs. In general, patients reported a small degree of side effects at end of RT, and there was no difference between groups for primary outcome (rectal bother scale of QUFW94 1.871 vs 1.884, p = 0.804). In addition, there were no significant differences between groups for any other gastrointestinal or urinary symptom as reported by QUFW94. Health related quality of life analyses (EORTC QLQ 30) demonstrated no differences between groups. INTERPRETATION: In radical RT for prostate cancer, daily CBCT IGRT with reduced PTV margins demonstrated no advantage with respect to patient reported side effects at end of RT as compared to weekly orthogonal offline portal imaging with standard PTV margins.
Authors: Mona Splinter; Ilias Sachpazidis; Tilman Bostel; Tobias Fechter; Constantinos Zamboglou; Christian Thieke; Oliver Jäkel; Peter E Huber; Jürgen Debus; Dimos Baltas; Nils H Nicolay Journal: Front Oncol Date: 2020-09-29 Impact factor: 6.244
Authors: Tilman Bostel; Ilias Sachpazidis; Mona Splinter; Nina Bougatf; Tobias Fechter; Constantinos Zamboglou; Oliver Jäkel; Peter E Huber; Dimos Baltas; Jürgen Debus; Nils H Nicolay Journal: Front Oncol Date: 2019-09-27 Impact factor: 6.244
Authors: Julia Murray; Clare Griffin; Sarah Gulliford; Isabel Syndikus; John Staffurth; Miguel Panades; Christopher Scrase; Chris Parker; Vincent Khoo; Jamie Dean; Helen Mayles; Philip Mayles; Simon Thomas; Olivia Naismith; Angela Baker; Helen Mossop; Clare Cruickshank; Emma Hall; David Dearnaley Journal: Radiother Oncol Date: 2019-11-22 Impact factor: 6.280
Authors: Mona Splinter; Tilman Bostel; Ilias Sachpazidis; Tobias Fechter; Constantinos Zamboglou; Oliver Jäkel; Peter E Huber; Jürgen Debus; Dimos Baltas; Nils H Nicolay Journal: Front Oncol Date: 2019-11-08 Impact factor: 6.244
Authors: Michael Yan; Andre G Gouveia; Fabio L Cury; Nikitha Moideen; Vanessa F Bratti; Horacio Patrocinio; Alejandro Berlin; Lucas C Mendez; Fabio Y Moraes Journal: Nat Rev Urol Date: 2021-08-13 Impact factor: 14.432