Abstract Purpose To assess quantitative signal intensity (SI) kinetics obtained from serial MRI of swallowing muscles as a potential imaging biomarker of radiation-induced dysphagia in oropharyngeal cancer (OPC) patients receiving radiotherapy (RT). Methods Patients were enrolled under an IRB approved Phase II/III randomized trial. Patients underwent serial MRIs at pre-, mid-, and post-RT. Normalized T1, T1+ contrast (T1 + C), and T2 SI for swallowing muscle volumes-of-interest (VOIs) were collected and delta SI changes (Δ) were calculated. Mid- and post-RT SI relative to baseline were assessed and correlations between radiation dose and percent change in SI were calculated. Independent samples’ t-tests were used to compare the percent change of SI between patients divided into two groups based on dysphagia status post-RT. Results Forty-six patients with stage III/IV HPV+ OPC were included in this study. Relative to baseline, mean T2 and T1 + C SIs for middle pharyngeal constrictor were both significantly higher at mid- and post-RT (p < 0.004 for all). Superior pharyngeal constrictor also showed a significant increase in T1 + C SI at mid-RT (p = 0.0004). Additional muscle VOIs showed significant changes post-RT, but not earlier at mid-RT. Both mid- and post-RT doses were significantly correlated with the percent change of normalized T2 and T1 + C SI for examined muscle VOIs (p < 0.002). Mean percent changes of normalized T2 SI at mid-RT relative to baseline for all muscle VOIs were significantly higher in patients who developed grade ≥2 dysphagia relative to patients with no/mild dysphasia (mean Δ%: 8.2% vs 1.9%; respectively, p = 0.002). However, at post-RT, these changes were only significant in T1 SI (11.2% vs −1.3%; p < 0.0001). Conclusion Signal intensity kinetics of radiation injury can be broadly correlated with the functional muscular defect. Serial MRI during the course of RT may provide an opportunity to quantitatively track muscular pathology for subclinical detection of patients at high risk to develop dysphagia.

Abstract Purpose To describe long-term failure pattern after early-stage breast cancer in relation to local treatment (breast-conserving therapy (BCT) or mastectomy) and age. Materials and methods Cohort study with balanced 5-year age groups and prospectively collected data; 813 Danish lymph-node-negative breast cancer patients diagnosed in 1989–98 and treated with mastectomy (N = 515) or BCT (N = 298) and no adjuvant systemic treatment. Results The 20-year local recurrence (LR) risk was 20% after BCT; 8.7% after mastectomy. LR developed in mastectomy patients within the first 10 years; in BCT patients throughout the entire 20-year period. Younger patients’ (⩽45 years) 20-year LR risk was generally higher than older patients’ (>45 years) (19% vs. 5%, p < 0.001). In younger patients, LR was significantly associated with distant metastasis (DM) (hazard ratio (HR) = 2.7(1.8–4.2)) and 20-year breast-cancer mortality (HR = 2.7(1.7–4.4)). BCT was associated with higher 20-year breast-cancer mortality (HR = 1.5(1.0–2.4)) and higher 20-year all-cause mortality (HR = 1.7(1.2–2.5)) than mastectomy. In older patients, LR was not associated with DM, and breast-cancer mortality was similar for BCT and mastectomy. Conclusion BCT patients with no adjuvant systemic treatment developed LR throughout 20-year period and faced higher LR risk than mastectomy patients. LR was associated with DM among younger patients, and younger BCT patients had higher mortality than younger mastectomy patients.

Abstract Background The objective of this HERO study was to assess the number of new cancer patients that will require at least one course of radiotherapy by 2025. Methods European cancer incidence data by tumor site and country for 2012 and 2025 was extracted from the GLOBOCAN database. The projection of the number of new cases took into account demographic factors (age and size of the population). Population based stages at diagnosis were taken from four European countries. Incidence and stage data were introduced in the Australian Collaboration for Cancer Outcomes Research and Evaluation (CCORE) model. Results Among the different tumor sites, the highest expected relative increase by 2025 in treatment courses was prostate cancer (24%) while lymphoma (13%), head and neck (12%) and breast cancer (10%) were below the average. Based on the projected cancer distributions in 2025, a 16% expected increase in the number of radiotherapy treatment courses was estimated. This increase varied across European countries from less than 5% to more than 30%. Conclusion With the already existing disparity in radiotherapy resources in mind, the data provided here should act as a leverage point to raise awareness among European health policy makers of the need for investment in radiotherapy.

Abstract Background and purpose Linac improvements in gantry speed, leaf speed and dose rate may increase the time-efficiency of volumetric modulated arc therapy (VMAT) delivery. The plan quality achievable with faster VMAT however remains to be investigated. In this study, a fast-rotating O-ring linac with fast-moving leaves is compared with a C-arm linac in terms of plan quality and delivery time for VMAT of head-and-neck cancer (HNC). Material and methods For 30 patients with HNC, treatment planning was performed using dual-arc (HA2) and triple-arc (HA3) VMAT on a Halcyon fast-rotating O-ring linac and using dual-arc VMAT on a TrueBeam C-arm linac (TB2). Target coverage metrics and complication probabilities were compared. Plan delivery was verified using 3%/3 mm gamma-index analysis of helical diode array measurements. Volumetric image acquisition and plan delivery times were compared. Results All studied VMAT-techniques fulfilled the target coverage objectives. D2% to the boost volume was higher for HA2 (median 103.7%, 1st–3rd quartile [103.5%;104.0%]) and HA3 (103.2% [103.0%;103.7%)] than for TB2 (102.6% [102.3%;103.0%)], resulting in an increased boost target dose heterogeneity for HA2 and HA3. Complication probabilities were comparable between HA2 and TB2, while HA3 showed a xerostomia probability reduction (0.8% [0.2%;1.8%]) and dysphagia probability reduction (1.0% [0.2%;1.8%]) compared with TB2. Gamma-index agreement scores were never below 93.0% for HA2, HA3 and TB2. Volumetric imaging and plan delivery time was shorter for HA2 (1 m 24 s ± 1 s) and HA3 (1 m 54 s ± 1 s) than for TB2 (2 m 47 s ± 1 s). Conclusion For VMAT of HNC, the fast-rotating O-ring linac at least maintains the plan quality of two arcs on a C-arm linac while reducing the image acquisition and plan delivery time.

Abstract Background and purpose Chemoradiotherapy (CRT) is the standard therapy for localized anal cancer (AC), but this treatment is associated with substantial toxicity. However, there is a lack of prospectively collected toxicity and patient reported outcome (PRO) data from larger cohorts. The purpose was to prospectively collect and determine agreement between physician assessed toxicity (CTCAE) and PRO during and after CRT and to compare IMRT, VMAT and proton-based planning in a subgroup of patients. Material and methods Patients, treated with CRT for AC, were included between 2015 and 2017. NCI-CTCAE v.4.0, EORTC QLQ-C30 and CR29 data were collected baseline, mid-therapy, end-of therapy and 2–4 weeks posttherapy. Treatment planning with 5- or 6-fixed field IMRT, 2 and 3 arc VMAT, and 3- and 4-field proton plans were compared. Results One-hundred patients were included. Both CTCAE and PROs related to acute toxicity reached a maximum at end of therapy. Incidences of PROs were markedly higher with only slight to fair agreement to CTCAE, (κ 13–37). Comparative planning revealed dosimetric equality of IMRT and VMAT plans, but superiority of proton plans. Conclusions The high incidence of PRO scores and weak agreement to CTCAE suggest that PROs are important tools complementary to CTCAE in evaluating patient symptoms during and after CRT. Proton therapy has the potential to lower radiation doses to most organs at risk.

Abstract Background and purpose In radiotherapy for rectum cancer, the target volume is highly deformable. An adaptive plan selection strategy can mitigate the effect of these variations. The purpose of this study was to evaluate the feasibility of an adaptive strategy by assessing the interobserver variation in CBCT-based plan selection. Material and methods Eleven patients with rectum cancer, treated with a non-adaptive strategy, were selected. Five CBCT scans were available per patient. To simulate the plan selection strategy, per patient three PTVs were created by varying the anterior upper mesorectum margin. For each CBCT scan, twenty observers selected the smallest PTV that encompassed the target volume. After this initial baseline measurement, the gold standard was determined during a consensus meeting, followed by a second measurement one month later. Differences between both measurements were assessed using the Wilcoxon signed-rank test. Results In the baseline measurement, the concordance with the gold standard was 69% (range: 60–82%), which improved to 75% (range: 60–87%) in the second measurement (p = 0.01). For the second measurement, 10% of plan selections were smaller than the gold standard. Conclusion With a plan selection consistency between observers of 75%, a plan selection strategy for rectum cancer patients is feasible.

Abstract Purpose The aim was to assess changes of tumour hypoxia during primary radiochemotherapy (RCT) for head and neck cancer (HNC) and to evaluate their relationship with treatment outcome. Material and methods Hypoxia was assessed by FMISO-PET in weeks 0, 2 and 5 of RCT. The tumour volume (TV) was determined using FDG-PET/MRI/CT co-registered images. The level of hypoxia was quantified on FMISO-PET as TBRmax (SUVmaxTV/SUVmean background). The hypoxic subvolume (HSV) was defined as TV that showed FMISO uptake ⩾1.4 times blood pool activity. Results Sixteen consecutive patients (T3–4, N+, M0) were included (mean follow-up 31, median 44 months). Mean TBRmax decreased significantly (p < 0.05) from 1.94 to 1.57 (week 2) and 1.27 (week 5). Mean HSV in week 2 and week 5 (HSV2 = 5.8 ml, HSV3 = 0.3 ml) were significantly (p < 0.05) smaller than at baseline (HSV1 = 15.8 ml). Kaplan–Meier plots of local recurrence free survival stratified at the median TBRmax showed superior local control for less hypoxic tumours, the difference being significant at baseline and after 2 weeks (p = 0.031, p = 0.016). Conclusions FMISO-PET documented that in most HNC reoxygenation starts early during RCT and is correlated with better outcome.

Abstract Purpose This study automatically quantified calcifications in coronary arteries (CAC) and thoracic aorta (TAC) on breast planning computed tomography (CT) scans and assessed its reproducibility compared to manual scoring. Material and Methods Dutch (n = 1199) and Singaporean (n = 1090) breast cancer patients with radiotherapy planning CT scan were included. CAC and TAC were automatically scored using deep learning algorithm. CVD risk categories were based on Agatson CAC: 0, 1–10, 11–100, 101–400 and >400. Reliability between automatic and manual scoring was assessed in 120 randomly selected CT scans from each population, with linearly weighted kappa for CAC categories and intraclass correlation coefficient for TAC. Results Median age was higher in Dutch patients than Singaporean patients: 57 versus 52 years. CAC and TAC increased with age and were more present in Dutch patients than Singaporean patients: 24.2% versus 17.3% and 73.0% versus 62.2%, respectively. Reliability of CAC categories and TAC was excellent in the Netherlands (0.85 (95% confidence interval (CI) = 0.77–0.93) and 0.98 (95% CI = 0.96–0.98) respectively) and Singapore (0.90 (95% CI = 0.84–0.96) and 0.99 (95% CI = 0.98–0.99) respectively). Conclusions CAC and TAC prevalence was considerable and increased with age. Deep learning software is a reliable method to automatically measure CAC and TAC on radiotherapy breast CT scans.

Summary Retrospective evaluation of 188 advanced stage non-small cell lung cancer patients treated with IMRT or VMAT revealed a limited increase of moderate to severe acute esophageal toxicity after VMAT. Acute pulmonary toxicity and severe late toxicity were low. Overall survival did not differ between the IMRT and VMAT groups.

Abstract Background/Purpose This study describes late bowel morbidity prospectively assessed in the multi-institutional EMBRACE study on MRI-guided adaptive brachytherapy in locally advanced cervical cancer (LACC). Materials/Methods A total of 1176 patients were analyzed. Physician reported morbidity (CTCAE v.3.0) and patient reported outcome (PRO) (EORTC QLQ C30/CX24) were assessed at baseline and at regular follow-up. Results At 3/5 years the actuarial incidence of bowel morbidity grade 3–4 was 5.0%/5.9%, including incidence of stenosis/stricture/fistula of 2.0%/2.6%. Grade 1–2 morbidity was pronounced with prevalence rates of 28–33% during follow-up. Diarrhea and flatulence were most frequently reported, significantly increased after 3 months and remained elevated during follow-up. Incontinence gradually worsened with time. PRO revealed high prevalence rates. Diarrhea ≥“a little” increased from 26% to 37% at baseline to 3 months and remained elevated, difficulty in controlling bowel increased from 11% to 26% at baseline to 3 months gradually worsening with time. Constipation and abdominal cramps improved after treatment. Conclusion Bowel morbidity reported in this large cohort of LACC patients was limited regarding severe/life-threatening events. Mild-moderate diarrhea, flatulence and incontinence were prevalent after treatment with PROs indicating a considerable and clinically relevant burden. Critical knowledge based on the extent and manifestation pattern of treatment-related morbidity will serve future patient management.