BackgroundTreatment for locally advanced rectal cancer (LARC) consists of chemoradiation therapy (CRT) and surgery. Approximately 15% of patients show a pathological complete response (pCR). Increased pCR-rates can be achieved through dose escalation, thereby increasing the number patients eligible for organ-preservation to improve quality of life (QoL). A randomized comparison of 65 versus 50Gy with external-beam radiation alone has not yet been performed. This trial investigates pCR rate, clinical response, toxicity, QoL and (disease-free) survival in LARC patients treated with 65Gy (boost + chemoradiation) compared with 50Gy standard chemoradiation (sCRT).Methods/designThis study follows the ‘cohort multiple randomized controlled trial’ (cmRCT) design: rectal cancer patients are included in a prospective cohort that registers clinical baseline, follow-up, survival and QoL data. At enrollment, patients are asked consent to offer them experimental interventions in the future. Eligible patients—histologically confirmed LARC (T3NxM0 <1 mm from mesorectal fascia, T4NxM0 or TxN2M0) located ≤10 cm from the anorectal transition who provided consent for experimental intervention offers—form a subcohort (n = 120). From this subcohort, a random sample is offered the boost prior to sCRT (n = 60), which they may accept or refuse. Informed consent is signed only after acceptance of the boost. Non-selected patients in the subcohort (n = 60) undergo sCRT alone and are not notified that they participate in the control arm until the trial is completed.sCRT consists of 50Gy (25 × 2Gy) with concomitant capecitabine. The boost (without chemotherapy) is given prior to sCRT and consists of 15 Gy (5 × 3Gy) delivered to the gross tumor volume (GTV). The primary endpoint is pCR (TRG 1). Secondary endpoints include acute grade 3–4 toxicity, good pathologic response (TRG 1-2), clinical response, surgical complications, QoL and (disease-free) survival. Data is analyzed by intention to treat.DiscussionThe boost is delivered prior to sCRT so that GTV adjustment for tumor shrinkage during sCRT is not necessary. Small margins also aim to limit irradiation of healthy tissue. The cmRCT design provides opportunity to overcome common shortcomings of classic RCTs, such as slow recruitment, disappointment-bias in control arm patients and poor generalizability.Trial registrationThe Netherlands Trials Register NL46051.041.13. Registered 22 August 2013. ClinicalTrials.gov NCT01951521. Registered 18 September 2013.

Purpose: Conventional techniques (3D-CRT) for craniospinal irradiation (CSI) are still widely used. Modern techniques (IMRT, VMAT, TomoTherapy V R , proton pencil beam scanning [PBS]) are applied in a limited number of centers. For a 14-year-old patient, we aimed to compare dose distributions of five CSI techniques applied across Europe and generated according to the participating institute protocols, therefore representing daily practice. Material and methods: A multicenter (n ¼ 15) dosimetric analysis of five different techniques for CSI (3D-CRT, IMRT, VMAT, TomoTherapy V R , PBS; 3 centers per technique) was performed using the same patient data, set of delineations and dose prescription (36.0/1.8 Gy). Different treatment plans were optimized based on the same planning target volume margin. All participating institutes returned their best treatment plan applicable in clinic. Results: The modern radiotherapy techniques investigated resulted in superior conformity/homogeneity-indices (CI/HI), particularly in the spinal part of the target (CI: 3D-CRT:0.3 vs. modern:0.6; HI: 3D-CRT:0.2 vs. modern:0.1), and demonstrated a decreased dose to the thyroid, heart, esophagus and pancreas. Dose reductions of >10.0 Gy were observed with PBS compared to modern photon techniques for parotid glands, thyroid and pancreas. Following this technique, a wide range in dosimetry among centers using the same technique was observed (e.g., thyroid mean dose: VMAT: 5.6-24.6 Gy; PBS: 0.3-10.1 Gy). Conclusions: The investigated modern radiotherapy techniques demonstrate superior dosimetric results compared to 3D-CRT. The lowest mean dose for organs at risk is obtained with proton therapy. However, for a large number of organs ranges in mean doses were wide and overlapping between techniques making it difficult to recommend one radiotherapy technique over another. ARTICLE HISTORY

Background and purpose: To reduce relapse risk, Total Body Irradiation (TBI) is part of conditioning regimens for hematopoietic stem cell transplantation (HSCT) in pediatric acute leukemia. The study purpose was to evaluate clinical practices regarding TBI, such as fractionation, organ shielding and delivery techniques, among SIOPE affiliated radiotherapy centers. Methods: An electronic survey was sent out to 233 SIOPE affiliated centers, containing 57 questions about clinical practice of TBI. Surveys could be answered anonymously. Results: From over 25 countries, 82 responses were collected. For TBI-performing centers, 40/48 irradiated 10 pediatric patients annually (range: 1-2 to >25). Most indications concerned acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Four different fractionation schedules were used, of which 12 Gy in 6 fractions was applied in 91% for ALL and 86% for AML. Dose reduction to the lungs, mostly to a mean dose of 8-10 Gy, was applied by 28/33 centers for ALL and 19/21 centers for AML, in contrast to much less applied dose reduction to the kidneys (7/33 ALL and 7/21 AML), thyroid (2/33 ALL and 2/21 AML), liver (4/33 ALL and 3/21 AML) and lenses (4/33 ALL and 4/21 AML). Conventional TBI techniques were used by 24/29 responding centers, while 5/29 used advanced optimized planning techniques. Conclusion: Across SIOPE, there is a high level of uniformity in fractionation and use of lung shielding. Practices vary regarding other organs-at-risk shielding and implementation of advanced techniques. A SIOPE radiotherapy working group will be established to define international guidelines for pediatric TBI.

Background and purpose: In pediatric renal tumors, conventional two opposing photon beams have been used to cover the postoperative flank target volume for decades. This single center study describes the locoregional outcome using highly conformal flank target volumes adjusted for postoperative changes and intra-fraction motion combined with Volumetric-Modulated Arc Therapy (VMAT). Materials and methods: Between 01-2015 and 12-2019, 36/161 newly diagnosed patients with renal tumors underwent flank only irradiation (n = 30) or flank + whole lung irradiation (n = 6) using highly conformal target volumes in line with the SIOP-RTSG consensus statement. VMAT consisted of full-arc 10MV photon beams optimized for constraints of the organs at risk. In case of locoregional relapses, image co-registration and dose reconstruction was performed. Each relapse was classified as either 'infield' (V95% relapse : 99.0%), 'marginal' (V95% relapse : 20.0-98.9%) or 'outfield' (V95% relapse : 0-19.9%). Results: At a median follow-up from diagnosis of 3.1 years (range:0.4-5.7), the estimated 2-year Locoregional Control Rate, Disease-Free Interval and Overall Survival were 94%, 91% and 94%, respectively. Locoregional relapse was observed in two patients. One patient had a combined tumor bed and regional recurrence, classified as infield (V95% relapse : 100%) and outfield (V95% relapse : 1.2%). The second patient had a regional relapse in the inferior vena cava classified as marginal recurrence (V95% relapse : 93%). Relapses would not have been adequately covered by conventional beams. Conclusions: This single center analysis provides encouraging evidence that excellent locoregional control can be obtained by using highly conformal flank target volumes with VMAT in pediatric renal tumors. The safety of this approach will be validated in a prospective multicenter study.

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Optic nerves are part of the craniospinal irradiation (CSI) target volume. Modern radiotherapy techniques achieve highly conformal target doses while avoiding organs-at-risk such as the lens. The magnitude of eye movement and its influence on CSI target-and avoidance volumes are unclear. We aimed to evaluate the movement-range of lenses and optic nerves and its influence on dose distribution of several planning techniques. Methods: Ten volunteers underwent MRI scans in various gaze directions (neutral, left, right, cranial, caudal). Lenses, orbital optic nerves, optic discs and CSI target volumes were delineated. 36-Gy cranial irradiation plans were constructed on synthetic CT images in neutral gaze, with Volumetric Modulated Arc Therapy, pencil-beam scanning proton therapy, and 3D-conventional photons. Movement-amplitudes of lenses and optic discs were analyzed, and influence of gaze direction on lens and orbital optic nerve dose distribution. Results: Mean eye structures' shift from neutral position was greatest in caudal gaze; − 5.8±1.2 mm (±SD) for lenses and 7.0±2.0 mm for optic discs. In 3D-conventional plans, caudal gaze decreased Mean Lens Dose (MLD). In VMAT and proton plans, eye movements mainly increased MLD and diminished D98 orbital optic nerve (D98 OON ) coverage; mean MLD increased up to 5.5 Gy [total ΔMLD range − 8.1 to 10.0 Gy], and mean D98 OON decreased up to 3.3 Gy [total ΔD98 OON range − 13.6 to 1.2 Gy]. VMAT plans optimized for optic disc Internal Target Volume and lens Planning organ-at-Risk Volume resulted in higher MLD over gaze directions. D98 OON became ≥95% of prescribed dose over 95/100 evaluated gaze directions, while all-gaze bilateral D98 OON significantly changed in 1 of 10 volunteers. Conclusion: With modern CSI techniques, eye movements result in higher lens doses and a mean detriment for orbital optic nerve dose coverage of <10% of prescribed dose.

Background and purpose: The aim of this study was to determine the feasibility of hypofractionated schedules for metastatic bone/bone marrow lesions in children and to investigate dosimetric differences to the healthy surrounding tissues compared to conventional schedules. Methods: 27 paediatric patients (mean age, 7 years) with 50 metastatic bone/bone marrow lesions (n = 26 cranial, n = 24 extra-cranial) from solid primary tumours (neuroblastoma and sarcoma) were included. The PTV was a 2 mm expansion of the GTV. A prescription dose of 36 and 54 Gy EQD2 a/b=10 was used for neuroblastoma and sarcoma lesions, respectively. VMAT plans were optimized for each single lesion using different fractionation schedules: conventional (30/20 fractions, V 95% ! 99%, D 0.1cm