Purpose
The Oriatron eRT6 is an experimental high dose‐per‐pulse linear accelerator (linac) which was designed to deliver an electron beam with variable dose‐rates, ranging from a few Gy/min up to ...hundreds of Gy/s. It was built to study the radiobiological effects of high dose‐per‐pulse/dose‐rate electron beam irradiation, in the context of preclinical and cognitive studies. In this work, we report on the commissioning and beam monitoring of the Oriatron eRT6 prototype linac.
Materials and Methods
The beam was characterized in different steps. The output stability was studied by performing repeated measurements over a period of 20 months. The relative output variations caused by changing beam parameters, such as the temporal electron pulse width, the pulse repetition frequency and the pulse amplitude were also analyzed. Finally, depth dose curves and field sizes were measured for two different beam settings, resulting in one beam with a conventional radiotherapy dose‐rate and one with a much higher dose‐rate. Measurements were performed with Gafchromic EBT3 films and with a PTW Advanced Markus ionization chamber. In addition, we developed a beam current monitoring system based on the signals from an induction torus positioned at the beam exit of the waveguide and from a graphite beam collimator.
Results
The stability of the output over repeated measurements was found to be good, with a standard deviation smaller than 1%. However, non‐negligible day‐to‐day variations of the beam output were observed. Those output variations showed different trends depending on the dose‐rate. The analysis of the relative output variation as a function of various beam parameters showed that in a given configuration, the dose‐rate could be reliably varied over three orders of magnitude. Interdependence effects on the output variation between the parameters were also observed. The beam energy and field size were found to be slightly dose‐rate‐dependent and suitable mainly for small animal irradiation. The beam monitoring system was able to measure in a reproducible way the total charge of electrons that exit the machine, as long as the electron pulse amplitude remains above a given threshold. Furthermore, we were able to relate the charge measured with the monitoring system to the absorbed dose in a solid water phantom.
Conclusion
The Oriatron eRT6 was successfully commissioned for preclinical use and is currently in full operation, with studies being performed on the radiobiological effects of high dose‐per‐pulse irradiation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Patients with acute myeloid leukemia (AML) in morphological first complete remission (CR1) pre‐allogeneic hematopoietic cell transplantation (HCT) may have measurable residual disease (MRD) by ...molecular and immunophenotyping criteria. We assessed interactions of MRD status with HCT conditioning regimen intensity in patients aged <50 years (y) or ≥50y. This was a retrospective study by the European Society for Blood and Marrow Transplantation registry. Patients were >18y with AML CR1 MRD NEG/POS and recipients of HCT in 2000‐2015. Conditioning regimens were myeloablative (MAC), reduced intensity (RIC) or non‐myeloablative (NMA). Outcomes included leukemia free survival (LFS), overall survival (OS), relapse incidence (RI), non‐relapse mortality (NRM), chronic graft‐vs‐host (cGVHD), and GVHD‐free and relapse‐free survival (GRFS). The 2292 eligible patients were categorized into four paired groups: <50y MRD POS MAC (N = 240) vs RIC/NMA (N = 58); <50y MRD NEG MAC (N = 665) vs RIC/NMA (N = 195); ≥50y MRD POS MAC (N = 126) vs RIC/NMA (N = 230), and ≥50y MRD NEG MAC (N = 223) vs RIC/NMA (N = 555). In multivariate analysis RIC/NMA was only inferior to MAC for patients in the <50y MRD POS group, with worse RI (HR 1.71) and LFS (HR 1.554). Patients <50Y MRD NEG had less cGVHD after RIC/NMA HCT (HR 0.714). GRFS was not significantly affected by conditioning intensity in any group. Patients aged <50y with AML CR1 MRD POS status should preferentially be offered MAC allo‐HCT. Prospective studies are needed to address whether patients with AML CR1 MRD NEG may be spared the toxicity of MAC regimens. New approaches are needed for ≥50y AML CR1 MRD POS.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Purpose
The purpose of this work was to establish an empirical model of the ion recombination in the Advanced Markus ionization chamber for measurements in high dose rate/dose‐per‐pulse electron ...beams. In addition, we compared the observed ion recombination to calculations using the standard Boag two‐voltage‐analysis method, the more general theoretical Boag models, and the semiempirical general equation presented by Burns and McEwen.
Methods
Two independent methods were used to investigate the ion recombination: (a) Varying the grid tension of the linear accelerator (linac) gun (controls the linac output) and measuring the relative effect the grid tension has on the chamber response at different source‐to‐surface distances (SSD). (b) Performing simultaneous dose measurements and comparing the dose–response, in beams with varying dose rate/dose‐per‐pulse, with the chamber together with dose rate/dose‐per‐pulse independent Gafchromic™ EBT3 film. Three individual Advanced Markus chambers were used for the measurements with both methods. All measurements were performed in electron beams with varying mean dose rate, dose rate within pulse, and dose‐per‐pulse (10−2 ≤ mean dose rate ≤ 103 Gy/s, 102 ≤ mean dose rate within pulse ≤ 107 Gy/s, 10−4 ≤ dose‐per‐pulse ≤ 101 Gy), which was achieved by independently varying the linac gun grid tension, and the SSD.
Results
The results demonstrate how the ion collection efficiency of the chamber decreased as the dose‐per‐pulse increased, and that the ion recombination was dependent on the dose‐per‐pulse rather than the dose rate, a behavior predicted by Boag theory. The general theoretical Boag models agreed well with the data over the entire investigated dose‐per‐pulse range, but only for a low polarizing chamber voltage (50 V). However, the two‐voltage‐analysis method and the Burns & McEwen equation only agreed with the data at low dose‐per‐pulse values (≤ 10−2 and ≤ 10−1 Gy, respectively). An empirical model of the ion recombination in the chamber was found by fitting a logistic function to the data.
Conclusions
The ion collection efficiency of the Advanced Markus ionization chamber decreases for measurements in electron beams with increasingly higher dose‐per‐pulse. However, this chamber is still functional for dose measurements in beams with dose‐per‐pulse values up toward and above 10 Gy, if the ion recombination is taken into account. Our results show that existing models give a less‐than‐accurate description of the observed ion recombination. This motivates the use of the presented empirical model for measurements with the Advanced Markus chamber in high dose‐per‐pulse electron beams, as it enables accurate absorbed dose measurements (uncertainty estimation: 2.8–4.0%, k = 1). The model depends on the dose‐per‐pulse in the beam, and it is also influenced by the polarizing chamber voltage, with increasing ion recombination with a lowering of the voltage.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
•Updated proposal for the selection of nodal target volumes in definitive radiotherapy is provided.•Recommendations for both negative and positive neck are provided.•The locations addressed are: oral ...cavity, oropharynx, hypopharynx, larynx, nasopharynx, paranasal sinuses, nasal cavity and carcinoma of unknown primary.•Recommendations are according to the latest neck node level terminology and staging.
In 2000, a panel of experts published a proposal for the selection of lymph node target volumes for definitive head and neck radiation therapy (Radiother Oncol, 2000; 56: 135–150). Hereunder, this selection is updated and extended to also cover primary sites not previously covered.
The lymphatic spread of head and neck cancers into neck lymph nodes was comprehensively reviewed based on radiological, surgical and pathological literature regarding both initial involvement and patterns of failure. Then a panel of worldwide head and neck radiotherapy experts agreed on a consensus for the selection of both high- and low-risk lymph node target volumes for the node negative and the node positive neck.
An updated selection of lymph node target volumes is reported for oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, paranasal sinuses, nasal cavity and carcinoma of unknown primary as a function of the nodal staging (UICC 8th edition).
The selection of lymph node target volumes for head and neck cancers treated with IMRT/VMAT or other highly conformal techniques (e.g. proton therapy) requires a rigorous approach. This updated proposal of selection should help clinicians for the selection of lymph nodes target volumes and contribute to increase consistency.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The term "stereotactic body radiotherapy" (SBRT) refers to high-precision radiotherapy techniques using numerous beams converging in a small target volume, allowing the delivery of high doses per ...fraction (>6-7 Gy) in a very few number of fractions ....
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Because a pediatric-inspired Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) protocol yielded a markedly improved outcome in adults with Philadelphia chromosome–negative ALL, we ...aimed to reassess the role of allogeneic stem cell transplantation (SCT) in patients treated in the GRAALL-2003 and GRAALL-2005 trials. In all, 522 patients age 15 to 55 years old and presenting with at least 1 conventional high-risk factor were candidates for SCT in first complete remission. Among these, 282 (54%) received a transplant in first complete remission. At 3 years, posttransplant cumulative incidences of relapse, nonrelapse mortality, and relapse-free survival (RFS) were estimated at 19.5%, 15.5%, and 64.7%, respectively. Time-dependent analysis did not reveal a significant difference in RFS between SCT and no-SCT cohorts. However, SCT was associated with longer RFS in patients with postinduction minimal residual disease (MRD) ≥10−3 (hazard ratio, 0.40) but not in good MRD responders. In B-cell precursor ALL, SCT also benefitted patients with focal IKZF1 gene deletion (hazard ratio, 0.42). This article shows that poor early MRD response, in contrast to conventional ALL risk factors, is an excellent tool to identify patients who may benefit from allogeneic SCT in the context of intensified adult ALL therapy. Trial GRAALL-2003 was registered at www.clinicaltrials.gov as #NCT00222027; GRAALL-2005 was registered as #NCT00327678.
•SCT in first complete remission is associated with 69.5% 3-year overall survival in high-risk ALL adult patients treated with intensified pediatric-like protocol.•Poor early MRD response is a powerful tool to select patients who may benefit from SCT in first complete remission.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Purpose The role of adjuvant chemotherapy (AC) or induction chemotherapy (IC) in the treatment of locally advanced nasopharyngeal carcinoma is controversial. The individual patient data from the ...Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma database were used to compare all available treatments. Methods All randomized trials of radiotherapy (RT) with or without chemotherapy in nonmetastatic nasopharyngeal carcinoma were considered. Overall, 20 trials and 5,144 patients were included. Treatments were grouped into seven categories: RT alone (RT), IC followed by RT (IC-RT), RT followed by AC (RT-AC), IC followed by RT followed by AC (IC-RT-AC), concomitant chemoradiotherapy (CRT), IC followed by CRT (IC-CRT), and CRT followed by AC (CRT-AC). P-score was used to rank the treatments. Fixed- and random-effects frequentist network meta-analysis models were applied. Results The three treatments with the highest probability of benefit on overall survival (OS) were CRT-AC, followed by CRT and IC-CRT, with respective hazard ratios (HRs 95% CIs) compared with RT alone of 0.65 (0.56 to 0.75), 0.77 (0.64 to 0.92), and 0.81 (0.63 to 1.04). HRs (95% CIs) of CRT-AC compared with CRT for OS, progression-free survival (PFS), locoregional control, and distant control (DC) were, respectively, 0.85 (0.68 to 1.05), 0.81 (0.66 to 0.98), 0.70 (0.48 to 1.02), and 0.87 (0.61 to 1.25). IC-CRT ranked second for PFS and the best for DC. CRT never ranked first. HRs of CRT compared with IC-CRT for OS, PFS, locoregional control, and DC were, respectively, 0.95 (0.72 to 1.25), 1.13 (0.88 to 1.46), 1.05 (0.70 to 1.59), and 1.55 (0.94 to 2.56). Regimens with more chemotherapy were associated with increased risk of acute toxicity. Conclusion The addition of AC to CRT achieved the highest survival benefit and consistent improvement for all end points. The addition of IC to CRT achieved the highest effect on DC.
Abstract Purpose The objective of this project was to define consensus guidelines for delineating organs at risk (OARs) for head and neck radiotherapy for routine daily practice and for research ...purposes. Methods Consensus guidelines were formulated based on in-depth discussions of a panel of European, North American, Asian and Australian radiation oncologists. Results Twenty-five OARs in the head and neck region were defined with a concise description of their main anatomic boundaries. The Supplemental material provides an atlas of the consensus guidelines, projected on 1 mm axial slices. The atlas can also be obtained in DICOM-RT format on request. Conclusion Consensus guidelines for head and neck OAR delineation were defined, aiming to decrease interobserver variability among clinicians and radiotherapy centers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We provide a long‐term evaluation of patients enrolled in the EORTC/GIMEMA AML‐10 trial which included a total of 2157 patients, 15‐60 years old, randomized to receive either daunorubicin (DNR, 50 ...mg/m2), mitoxantrone (MXR, 12 mg/m2), or idarubicin (IDA, 10 mg/m2) in addition to standard‐dose cytarabine and etoposide for induction chemotherapy and intermediate dose cytarabine for consolidation. Younger patients who reached complete remission with complete (CR) or incomplete (CRi) recovery were then scheduled to receive an allogeneic hematopoietic stem cell transplantation (HSCT). That was if they had a HLA‐identical sibling donor; in all other cases, an autologous HSCT had to be administered. At an 11‐year median follow‐up, the 5‐year, 10‐year and 15‐year overall survival (OS) rates were 33.2%, 30.1% and 28.0%, respectively. No significant difference between the three randomized groups regarding OS was observed (P = .38). In young patients, 15‐45 years old, no treatment difference (P = .89) regarding OS was observed, while in patients 46‐60 years old, MXR and IDA groups had a trend for a longer OS as compared to the DNR group (P = .029). Among younger patients without a favorable MRC cytogenetic risk subgroup who achieved a CR/CRi after induction chemotherapy, those with a HLA‐identical sibling donor had higher 10‐year and 15‐year OS rates than those without. In older patients who reached CR/CRi, the long‐term outcomes of those with or without a donor was similar. In conclusion, long‐term outcomes of the study confirmed similar OS in the three randomized groups in the whole cohort of patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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