Mature results from a Swedish comparison study of conventional versus accelerated radiotherapy in head and neck squamous cell carcinoma – The ARTSCAN trial

Zackrisson, Björn; Kjellén, Elisabeth; Söderstrom, Karin; Brun, Eva; Nyman, Jan; Friesland, Signe; Reizenstein, Johan; Sjödin, Helena; Ekberg, Lars; Lödén, Britta; Franzén, Lars; Ask, Anders; Wickart-Johansson, Gun; Lewin, Freddi; Björk‐Eriksson, Thomas; Lundin, Erik; Dalianis, Tina; Wennerberg, Johan; Johansson, Karl-Axel; Nilsson, Per

doi:10.1016/j.radonc.2015.09.024

Cited by 27 publications

(16 citation statements)

References 28 publications

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“…The control group of a four-arm trial 4 was triplicated (ie, data for patients in the control group were copied twice to have three control arms to compare with each experimental arm), a 2 × 2 trial (EORTC 22962 45 ) included three relevant comparisons for the meta-analysis, and three three-arm trials 36,37,55 included two relevant comparisons. The 33 trials included in the analysis of fractionation schedules (comparison 1) were divided into four predefined subgroups, depending on the type of radiotherapy: hyperfractionation (eight comparisons, including the unpublished EORTC 22962 trial), 4,33,44,45,49,50,56 moderately accelerated radiotherapy (19 comparisons), 2,4,30,32,34–39,41,42,46,54,55,57–59 very accelerated radiotherapy (seven comparisons, including the unpublished CHARTWEL trial), 3,47,51–53,60 and moderately hypofractionated (dose per fraction between 2–2·5 Gy [two comparisons]; 31,40 appendix pp 17–18). After discussion with the steering committee, the moderately hypofractionated trials were included in the moderately accelerated radiotherapy group.…”

Section: Resultsmentioning

confidence: 99%

Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis

Lacas

Bourhis

Overgaard

et al. 2017

The Lancet Oncology

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Summary Background The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials. Methods For this updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered fractionation radiotherapy (comparison 1) or conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone (comparison 2). Eligible trials had to start randomisation on or after Jan 1, 1970, and completed accrual before Dec 31, 2010; had to have been randomised in a way that precluded prior knowledge of treatment assignment; and had to include patients with non-metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing first-line curative treatment. Trials including a non-conventional radiotherapy control group, investigating hypofractionated radiotherapy, or including mostly nasopharyngeal carcinomas were excluded. Trials were grouped in three types of altered fractionation: hyperfractionated, moderately accelerated, and very accelerated. Individual patient data were collected and combined with a fixed-effects model based on the intention-to-treat principle. The primary endpoint was overall survival. Findings Comparison 1 (conventional fractionation radiotherapy vs altered fractionation radiotherapy) included 33 trials and 11 423 patients. Altered fractionation radiotherapy was associated with a significant benefit on overall survival (hazard ratio [HR] 0·94, 95% CI 0·90–0·98; p=0·0033), with an absolute difference at 5 years of 3·1% (95% CI 1·3–4·9) and at 10 years of 1·2% (−0·8 to 3·2). We found a significant interaction (p=0·051) between type of fractionation and treatment effect, the overall survival benefit being restricted to the hyperfractionated group (HR 0·83, 0·74–0·92), with absolute differences at 5 years of 8·1% (3·4 to 12·8) and at 10 years of 3·9% (−0·6 to 8·4). Comparison 2 (conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone) included five trials and 986 patients. Overall survival was significantly worse with altered fractionation radiotherapy compared with concomitant chemoradiotherapy (HR 1·22, 1·05–1·42; p=0·0098), with absolute differences at 5 years of −5·8% (−11·9 to 0·3) and at 10 years of −5·1% (−13·0 to 2·8). Interpretation This up...

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Section: Resultsmentioning

confidence: 99%

Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis

Lacas

Bourhis

Overgaard

et al. 2017

The Lancet Oncology

Self Cite

262

177

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“…Of the 17 institution‐matched OPSCC studies, the pooled proportion that was HPV‐positive was 0.60 (95%CI: 0.45–0.74), albeit with high heterogeneity of results across studies ( p heterogeneity <0.0001, I 2 = 0.99). On average, the HPV prevalence of OPSCC was 10% higher than SCCUPHN (95%CI: 1–19%; p < 0.0001; Fig.…”

Section: Resultsmentioning

confidence: 99%

Human papillomavirus and p16 immunostaining, prevalence and prognosis of squamous carcinoma of unknown primary in the head and neck region

Ren

Wen

et al. 2019

Intl Journal of Cancer

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Science searches, observational studies and clinical trials that reported survival rates of patients with SCCUPHN by HPV status were identified. Meta-analysis estimated the prevalence and prognosis (overall survival, OS; progression-free survival, PFS) of SCCUPHN by HPV status, and compared them to studies of oropharyngeal squamous cell carcinoma (OPSCC) from the same institutions and across continents. In 17 SCCUPHN studies (n = 1,149) and 17 institution-matched OPSCC studies (n = 6,522), the pooled HPV prevalence of SCCUPHN was 49%, which was only 10% (95%CI: 1-19%) lower than OPSCC prevalence in the underlying population. Estimated 5-year OS for HPV-negative SCCUPHN was 44% (95%CI: 36-51%) vs. HPV-positive SCCUPHN of 91% (95%CI: 86-96%); hazard ratio (HR) for OS was 3.25 (95%CI: 2.45-4.31) and PFS was 4.49 (95%CI: 2.88-7.02). HRs by HPV status for OPSCC were similar to that in SCCUPHN. While North American SCCUPHNs had higher HPV prevalence than European SCCUPHNs (OR = 2.68 (95%CI: 1.3-5.6)), HR of OS for HPV-negative vs. HPV-positive patients were similar in both continents (HRs of 3.78-4.09). Prevalence of HPV among SCCUPHN patients were lower than in OPSCC. The survival benefit conferred by being HPV-positive was similar in SCCUPHN as in OPSCCs, independent of continent.

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“…24 The result of this analysis was a displacement vector field map showing the difference in marker positions calculated by inverse mapping. 32 We used patient CT images from the prospective Swedish phase 3 multicenter randomized control study, ARTSCAN, 30 to estimate patient-induced susceptibility effects. All patients were scanned in the supine head-first position either on a Philips Brilliance Big Bore (120 kV voltage, 113-320 mA tube current) using an in-plane resolution of 1.07 Â 1.07 mm 2 or a Siemens Emotion 6 (130 KV voltage, 88 mAs tube current) CT camera with a resolution of 0.97 Â 0.97 mm 2 .…”

Section: Methods and Materials Distortion Quantification: Gradient Nomentioning

confidence: 99%

“…The CT images were for patients with oropharyngeal and oral cavity cancers included in the prospective Swedish phase 3 multicenter randomized control study, ARTSCAN. 30 We investigated the combined effect of simulated patient-induced susceptibility effects and phantom-measured residual MRI system distortions after 3D gradient nonlinearity correction on head and neck RTP at 3 T. Shimming on a modern scanner could be done either over the entire imaging volume or over a user-defined volume. Our first step was to identify the most clinically relevant strategy for this treatment region.…”

Section: Introductionmentioning

confidence: 99%

Dosimetric Impact of MRI Distortions: A Study on Head and Neck Cancers

Adjeiwaah

Bylund

Lundman

et al. 2019

International Journal of Radiation Oncology*Biology*Physics

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The dosimetric impact of distortions on 21 head and neck cancer magnetic resonanceeonly radiation therapy treatment plans was studied. Distorted computed tomography (CT) images were obtained by deforming patient CT scans with displacement fields from residual system and patientinduced susceptibility effects. The feasibility of magnetic resonanceeonly radiation therapy was demonstrated by a dose difference of less than 2% within the target volume for all dosimetric parameters evaluated between distorted CT and CT treatment plans. Purpose: To evaluate the effect of magnetic resonance (MR) imaging (MRI) geometric distortions on head and neck radiation therapy treatment planning (RTP) for an MRI-only RTP. We also assessed the potential benefits of patient-specific shimming to reduce the magnitude of MR distortions for a 3-T scanner. Methods and Materials: Using an in-house Matlab algorithm, shimming within entire imaging volumes and user-defined regions of interest were simulated. We deformed 21 patient computed tomography (CT) images with MR distortion fields (gradient nonlinearity and patient-induced susceptibility effects) to create distorted CT (dCT) images using bandwidths of 122 and 488 Hz/mm at 3 T. Field parameters from volumetric modulated arc therapy plans initially optimized on dCT data sets were transferred to CT data to compute a new plan. Both plans were compared to determine the impact of distortions on dose distributions. Results: Shimming across entire patient volumes decreased the percentage of voxels with distortions of more than 2 mm from 15.4% to 2.0%. Using the user-defined region of interest (ROI) shimming strategy, (here the Planning target volume (PTV) was the chosen ROI volume) led to increased geometric for volumes outside the PTV, as such voxels within the spinal cord with geometric shifts above 2 mm increased from 11.5% to 32.3%. The worst phantom-measured residual system distortions after 3dimensional gradient nonlinearity correction within a radial distance of 200 mm from the isocenter was 2.17 mm. For all patients, voxels with distortion shifts of more than 2 mm resulting from patient-induced susceptibility effects were 15.4% and 0.0% using bandwidths of 122 Hz/mm and 488 Hz/mm at 3 T. Dose differences between dCT and

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Mature results from a Swedish comparison study of conventional versus accelerated radiotherapy in head and neck squamous cell carcinoma – The ARTSCAN trial

Cited by 27 publications

References 28 publications

Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis

Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis

Human papillomavirus and p16 immunostaining, prevalence and prognosis of squamous carcinoma of unknown primary in the head and neck region

Dosimetric Impact of MRI Distortions: A Study on Head and Neck Cancers

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