Aim:Determination of impact of variations during voluntary moderately deep inspiration breath hold (vmDIBH) on doses to organs at risk (OAR) and target coverage in patients undergoing radiotherapy (RT) for left-sided breast cancer (BC). Methods:We recorded vmDIBH-breathing signals using a Surface Guidance system, without visual coaching, in 21 BC patients. In 13 patients, cone-beam CT (CBCT) scans were acquired with vmDIBH, immediately after treatment delivery. A 3D dose recalculation was performed on CBCT, cranio-caudally stitched with the planning CT for full dose evaluation. Mean Heart Dose (MHD), Mean Lung Dose (MLD) and V95% of the clinical target volume (CTV) were calculated. Relationships between vmDIBH level, stability and differences in Dose-Volume Histogram (DVH) parameters were analysed using linear regression and Mann-Whitney U-tests. Results:Of 150 recorded vmDIBHs, 39% of the breath-holds were within a predefined 3 mm gating window. The average deviation from this window was 0.6 mm (SD 1.9 mm), with the mean value just outside predefined boundaries. All recalculated CBCTs (n = 95) met predefined DVH criteria for MHD, MLD, and V95% of tumourbed CTV. The V95% of the whole breast CTV showed minor deviations from the planned dose (mean delta V95%: -0.8%, SD 1.6%). For patients with excursions beyond the 3 mm window, average differences were 1.43% in V95%-CTV, 0.02 Gy in MHD, and 0.05 Gy in MLD. Conclusion:Only small breathing excursions beyond 3 mm were observed during vmDIBH without visual coaching, not resulting in clinically relevant CTV Underdosage with MHD and MLD remaining within tolerance.

We report a case of a 32-week pregnant patient (at the initial radiotherapy intake) with stage III small cell lung cancer (SCLC) treated with concurrent chemo-proton radiotherapy.A total dose of 45 Gy(RBE) was delivered in 30 fractions (1.5 Gy(RBE) twice daily). Fetal dose estimates were calculated for both photon and proton radiotherapy scenarios. Synthetic CTs (sCTs) generated from daily cone-beam CTs (CBCT) enabled daily dose evaluation and treatment dose accumulation while minimizing imaging dose.The estimated cumulative fetal dose was 45.5 mSv, versus an estimated 182 mSv (without shielding) if photon therapy had been used for the whole treatment. Using sCTs instead of repeated weekly CTs saved 6 mSv. One plan adaptation was necessary after 10 days of treatment due to tumor shrinkage. The accumulated V95% of the clinical target volume (CTV) computed on the sCTs remained above 96.5% during the whole treatment course. A healthy boy was delivered at 37.5 weeks.This case illustrates how proton therapy and sCTs can safely minimize fetal exposure in pregnant patients requiring thoracic radiotherapy, even in the third trimester.

Supplementary Figure S1: Example of the FDG and HX4 parameters (FDG-SUVmean, HX4-SUVmean and HX4-TBR) sub-classified by tumor pathology. Adenocarcinoma (AC), squamous cell carcinoma (SCC), large cell carcinoma (LCC).

Supplementary Tables S1-S3. Supplementary Table S1: Patient characteristics. Supplementary Table S2 Pearson's correlation coefficient (R) and corresponding p-values of GTVln based parameters on FDG Supplementary Table S3: Average distribution (mean+SD) of high (+) and low (-), HX4 and FDG uptake within the primary GTV.

Background and purpose: Image-guided radiotherapy using cone beam-CT (CBCT) images is used to eval-uate patient anatomy and positioning before radiotherapy. In this study we analyzed and optimized a traffic light protocol (TLP) used in lung cancer patients to identify patients requiring treatment adapta-tion. Materials and methods: First, CBCT review requests of 243 lung cancer patients were retrospectively ana-lyzed and divided into 6 pre-defined categories. Frequencies and follow-up actions were scored. Based on these results, the TLP was optimized and evaluated in the same way on 230 patients treated in 2018. Results: In the retrospective study, a total of 543 CBCT review requests were created during treatment in 193/243 patients due to changed anatomy of lung (24%), change of tumor volume (24%), review of match (18%), shift of the mediastinum (15%), shift of tumor (15%) and other (4%). The majority of requests (474, 87%) did not require further action. In 6% an adjustment of the match criteria sufficed; in 7% treatment plan adaptation was required. Plan adaptation was frequently seen in the categories changed anatomy of lung, change of tumor volume and shift of tumor outside the PTV. Shift of mediastinum outside PRV and shift of GTV outside CTV (but inside PTV) never required plan adaptation and were omitted to opti-mize the TLP, which reduced the CBCT review requests by 23%.Conclusions: The original TLP selected patients that required a treatment adaptation, but with a high false positive rate. The optimized TLP reduced the amount of CBCT review requests, while still correctly iden-tifying patients requiring adaptation.(c) 2022 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 175 (2022) 152-158 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background and purpose: Dose painting by numbers (DPBN) require a high degree of dose modulation to fulfill the image-based voxel wise dose prescription. The aim of this study was to assess the dosimetric accuracy of 18Ffluoro-2-deoxy-glucose positron emission tomography(18F-FDG-PET)-based DPBN in an anthropomorphic lung phantom using alanine dosimetry. Materials and methods: A linear dose prescription based on 18F-FDG-PET image intensities within the gross tumor volume (GTV) of a lung cancer patient was employed. One DPBN scheme with low dose modulation (Scheme A; minimum/maximum fraction dose to the GTV 2.92/4.26 Gy) and one with a high modulation (Scheme B; 2.81/ 4.52 Gy) were generated. The plans were transferred to a computed tomograpy (CT) scan of a thorax phantom based on CT images of the patient. Using volumetric modulated arc therapy (VMAT), DPBN was delivered to the phantom with embedded alanine dosimeters. A plan was also delivered to an intentionally misaligned phantom. Absorbed doses at various points in the phantom were measured by alanine dosimetry. Results: A pointwise comparison between GTV doses from prescription, treatment plan calculation and VMAT delivery showed high correspondence, with a mean and maximum dose difference of <0.1 Gy and 0.3 Gy, respectively. No difference was found in dosimetric accuracy between scheme A and B. The misalignment caused deviations up to 1 Gy between prescription and delivery. Conclusion: DPBN can be delivered with high accuracy, showing that the treatment may be applied correctly from a dosimetric perspective. Still, misalignment may cause considerable dosimetric erros, indicating the need for patient immobilization and monitoring.

Abstract Background and purpose Reducing breathing motion in radiotherapy (RT) is an attractive strategy to reduce margins and better spare normal tissues. The objective of this prospective study (NCT03729661) was to investigate the feasibility of irradiation of non-small cell lung cancer (NSCLC) with visually guided moderate deep inspiration breath-hold (IBH) using nasal high-flow therapy (NHFT). Material and methods Locally advanced NSCLC patients undergoing photon RT were given NHFT with heated humidified air (flow: 40 L/min with 80% oxygen) through a nasal cannula. IBH was monitored by optical surface tracking (OST) with visual feedback. At a training session, patients had to hold their breath as long as possible, without and with NHFT. For the daily cone beam CT (CBCT) and RT treatment in IBH, patients were instructed to keep their BH as long as it felt comfortable. OST was used to analyze stability and reproducibility of the BH, and CBCT to analyze daily tumor position. Subjective tolerance was measured with a questionnaire at 3 time points. Results Of 10 included patients, 9 were treated with RT. Seven (78%) completed the treatment with NHFT as planned. At the training session, the mean BH length without NHFT was 39 s (range 15–86 s), and with NHFT 78 s (range 29–223 s) (p = .005). NHFT prolonged the BH duration by a mean factor of 2.1 (range 1.1–3.9s). The mean overall stability and reproducibility were within 1 mm. Subjective tolerance was very good with the majority of patients having no or minor discomfort caused by the devices. The mean inter-fraction tumor position variability was 1.8 mm (-1.1–8.1 mm;SD 2.4 mm). Conclusion NHFT for RT treatment of NSCLC in BH is feasible, well tolerated and significantly increases the breath-hold duration. Visually guided BH with OST is stable and reproducible. We therefore consider this an attractive patient-friendly approach to treat lung cancer patients with RT in BH.

Objectives: The aim of this work was to evaluate the operation of the 1600SRS detector and to develop a calibration procedure for verifying the dose delivered by a single isocenter stereotactic radiosurgery (SRS) treatment of small multiple brain metastases (BM). Methods: 14 clinical treatment cases were selected with the number of BM ranging from 2 to 11. The dosimetric agreement was investigated between the calculated and the measured dose by an OCTAVIUS 1600SRS array detector in an OCTAVIUS 4D phantom equipped with dedicated SRS top. The cross-calibration procedure deviated from the manufacturer’s as it applied field sizes and dose rates corresponding to the volumetric modulated arc therapy segments in each plan. Results: Measurements with a plan specific cross-calibration showed mean ± standard deviation (SD) agreement scores for cut-off values 50%, 80%, 95%, of 98.6 ± 1.7%, 96.5 ± 4.6%, 97.3 ± 4.4% for the 6 MV plans respectively, and 98.6 ± 1.5%, 96.6 ± 4.0% 96.4 ± 6.3%, for the 6 MV flattening filter free (FFF) plans respectively. Using the default calibration procedure instead of the plan specific calibration could lead to a combined systematic dose offset of 4.1% for our treatment plans. Conclusion: The 1600SRS detector array with the 4D phantom offers an accurate solution to perform routine quality assurance measurements of single isocenter SRS treatments of multiple BM. This work points out the necessity of an adapted cross-calibration procedure. Advances in knowledge: A dedicated calibration procedure enables accurate dosimetry with the 1600SRS detector for small field single isocenter SRS treatment of multiple brain metastases for a large amount of BM.

Purpose Modern computed tomography (CT) scanners have an extended field‐of‐view (eFoV) for reconstructing images up to the bore size, which is relevant for patients with higher BMI or non‐isocentric positioning due to fixation devices. However, the accuracy of the image reconstruction in eFoV is not well known since truncated data are used. This study introduces a new deep learning‐based algorithm for extended field‐of‐view reconstruction and evaluates the accuracy of the eFoV reconstruction focusing on aspects relevant for radiotherapy. Methods A life‐size three‐dimensional (3D) printed thorax phantom, based on a patient CT for which eFoV was necessary, was manufactured and used as reference. The phantom has holes allowing the placement of tissue mimicking inserts used to evaluate the Hounsfield unit (HU) accuracy. CT images of the phantom were acquired using different configurations aiming to evaluate geometric and HU accuracy in the eFoV. Image reconstruction was performed using a state‐of‐the‐art reconstruction algorithm (HDFoV), commercially available, and the novel deep learning‐based approach (HDeepFoV). Five patient cases were selected to evaluate the performance of both algorithms on patient data. There is no ground truth for patients so the reconstructions were qualitatively evaluated by five physicians and five medical physicists. Results The phantom geometry reconstructed with HDFoV showed boundary deviations from 1.0 to 2.5 cm depending on the volume of the phantom outside the regular scan field of view. HDeepFoV showed a superior performance regardless of the volume of the phantom within eFOV with a maximum boundary deviation below 1.0 cm. The maximum HU (absolute) difference for soft issue inserts is below 79 and 41 HU for HDFoV and HDeepFoV, respectively. HDeepFoV has a maximum deviation of −18 HU for an inhaled lung insert while HDFoV reached a 229 HU difference. The qualitative evaluation of patient cases shows that the novel deep learning approach produces images that look more realistic and have fewer artifacts. Conclusion To be able to reconstruct images outside the sFoV of the CT scanner there is no alternative than to use some kind of extrapolated data. In our study, we proposed and investigated a new deep learning‐based algorithm and compared it to a commercial solution for eFoV reconstruction. The deep learning‐based algorithm showed superior performance in quantitative evaluations based on phantom data and in qualitative assessments of patient data.

PurposeModern type ‘c’ dose calculation algorithms like Acuros® can predict dose for lung tumors larger than approximately 4 cm3 with a relative uncertainty up to 5%. However, increasingly better tumor diagnostics are leading to the detection of very small early‐stage lung tumors that can be treated with stereotactic body radiotherapy (SBRT) for inoperable patients. This raises the question whether dose algorithms like Acuros® can still accurately predict dose within 5% for challenging conditions involving small treatment fields. Current recommendations for Quality Assurance (QA) and dose verification in SBRT treatments are to use phantoms that are as realistic as possible to the clinical situation, although water‐equivalent phantoms are still largely used for dose verification. In this work we aim to demonstrate that existing dose verification methods are inadequate for accurate dose verification in very small lung tumors treated with SBRT.MethodThe homogeneous PTW Octavius4D phantom with the Octavius 1000 SRS detector (“Octavius4D phantom”) and the heterogeneous CIRS Dynamic Thorax phantom (‘CIRS phantom’) were used for dose measurements. The CIRS phantom contained different lung‐equivalent film‐holding cylindrical phantom inserts (“film inserts”) with water‐equivalent spherical targets with diameters 0.5, 0.75, 1, 2, and 3 cm. Plans were calculated for 6 and 10 MV for each spherical target in the CIRS phantom, resulting in 14 treatment plans. The plans were delivered to both Octavius4D and CIRS phantom to compare measured dose in a commonly used homogeneous and more realistic heterogeneous phantom setup. In addition, treatment plans of seven clinical lung cancer patients with lung tumors below approximately 1.0 cm3 were irradiated in the heterogeneous CIRS phantom. The actual tumor size within the clinical treatment plans determined the choice of the spherical target size, such that both measurement geometry and clinical target volumes match as closely as possible. The Acuros® dose algorithm (version 15.5.11) was used for all dose calculations reporting dose‐to‐medium using a 0.1‐cm‐grid size.ResultsThe measurement discrepancies in the homogeneous Octavius4D phantom for the fourteen treatment plans were within 1.5%. Dose discrepancies between measurement and treatment planning systems (TPS) for the heterogeneous CIRS phantom increased for both 6 and 10 MV with decreasing target diameters up to 23.7 ± 1.0% for 6 MV and 8.8 ± 1.1% for 10 MV for the smallest target of 0.5 cm in diameter with a 2‐mm‐CTV‐PTV margin. For the seven clinical plans this trend of increasing dose difference with decreasing tumor size is less pronounced although the smallest tumors show the largest differences between measurement and TPS up to 16.6 ± 0.9%.ConclusionCurrent verification methods using homogenous phantoms are not adequate for lung tumors with diameters below approximately 0.75 cm. The current Acuros® dose calculation algorithm underestimates dose in very small lung tumors. Dose verification of small lung tumors should be performed in an anthropomorphic lung phantom incorporating a water‐equivalent target that matches clinical tumor size as closely as possible.

To evaluate the accuracy of a commercial optical surface tracking (OST) system and to demonstrate how it can be implemented to monitor patient positioning during non-coplanar single isocenter stereotactic treatments of brain metastases. A 3-camera OST system was used (Catalyst HD (TM), C-RAD) on a TruebeamSTx with a 6DoF couch. The setup accuracy and agreement between the OST system, and CBCT and kV-MV imaging at couch angles 0 degrees and 270 degrees, respectively, were examined. Film measurements at 3 depths in the Rando-Alderson phantom were performed using a single isocenter non-coplanar VMAT plan containing 4 brain lesions. Setup of the phantom was performed with CBCT at couch 0 degrees and subsequently monitored by OST at other couch angles. Setup data for 7 volunteers were collected to evaluate the accuracy and reproducibility of the OST system at couch angles 0 degrees, 45 degrees, 90 degrees, 315 degrees, and 270 degrees. These results were also correlated to the couch rotation offsets obtained by a Winston-Lutz (WL) test. The Rando-Alderson phantom, as well as volunteers, were fixated using open face masks (Orfit). For repeated tests with the Rando-Alderson phantom, deviations between rotational and translational isocenter corrections for CBCT and OST systems are always within 0.2 degrees (pitch, roll, yaw), and 0.1mm and 0.5mm (longitudinal, lateral, vertical) for couch positions 0 degrees and 270 degrees, respectively. Dose deviations between the film and TPS doses in the center of the 4 lesions were -1.2%, -0.1%, -0.0%, and -1.9%. Local gamma evaluation criteria of 2%/2 mm and 3%/1 mm yielded pass rates of 99.2%, 99.2%, 98.6%, 89.9% and 98.8%, 97.5%, 81.7%, 78.1% for the 4 lesions. Regarding the volunteers, the mean translational and rotational isocenter shift values were (0.24 +/- 0.09) mm and (0.15 +/- 0.07) degrees. Largest isocenter shifts were found for couch angles 45 & x2da; and 90 & x2da;, confirmed by WL couch rotation offsets. Patient monitoring during non-coplanar VMAT treatments of brain metastases is feasible with submillimeter accuracy.

BACKGROUND:Stage III non-small cell lung cancer (NSCLC) still has a poor prognosis. Prior studies with individualized, accelerated, isotoxic dose escalation (INDAR) with 3D-CRT showed promising results, especially in patients not treated with concurrent chemo-radiotherapy. We investigated if INDAR delivered with IMRT would improve the overall survival (OS) of stage III NSCLC patients treated with concurrent chemotherapy and radiotherapy. PATIENTS AND METHODS:Patients eligible for concurrent chemo-radiotherapy were entered in this prospective study. Radiotherapy was given to a dose of 45 Gy/30 fractions BID (1.5 Gy/fraction), followed by QD fractions of 2 Gy until a total dose determined by the normal tissue constraints. The primary endpoint was OS, secondary endpoints were loco-regional relapses and toxicity. RESULTS:From May 4, 2009 until April 26, 2012, 185 patients were included. The mean tumor dose was 66.0 ± 12.8 Gy (36-73 Gy), delivered in a mean of 39.7 fractions in an overall treatment time of 38.2 days. The mean lung dose (MLD) was 17.3 Gy. The median OS was 19.8 months (95% CI 17.3-22.3) with a 5-year OS of 24.3%. Loco-regional failures as first site of recurrence occurred in 59/185 patients (31.8%). Isolated nodal failures (INF) were observed in 3/185 patients (1.6%). Dyspnea grade 3 was seen in 3.2% of patients and transient dysphagia grade 3 in 22%. CONCLUSIONS:INDAR with IMRT concurrently with chemotherapy did not lead to a sign of an improved OS in unselected stage III NSCLC patients.

Purpose The aim of this study was to evaluate experimentally the accuracy of the dose calculation algorithm AcurosXB in small field highly modulated Volumetric Modulated Arc Therapy (VMAT). Method The 1000SRS detector array inserted in the rotational Octavius 4D phantom (PTW) was used for 3D dose verification of VMAT treatments characterized by small to very small targets. Clinical treatment plans (n = 28) were recalculated on the phantom CT data set in the Eclipse TPS. All measurements were done on a Varian TrueBeamSTx, which can provide the jaw tracking technique (JTT). The effect of disabling the JTT, thereby fixing the jaws at static field size of 3 × 3 cm2 and applying the MLC to shape the smallest apertures, was investigated for static fields between 0.5 × 0.5−3 × 3 cm2 and for seven VMAT patients with small brain metastases. The dose calculation accuracy has been evaluated by comparing the measured and calculated dose outputs and dose distributions. The dosimetric agreement has been presented by a local gamma evaluation criterion of 2%/2 mm. Results Regarding the clinical plans, the mean ± SD of the volumetric gamma evaluation scores considering the dose levels for evaluation of 10%, 50%, 80% and 95% are (96.0 ± 6.9)%, (95.2 ± 6.8)%, (86.7 ± 14.8)% and (56.3 ± 42.3)% respectively. For the smallest field VMAT treatments, discrepancies between calculated and measured doses up to 16% are obtained. The difference between the 1000SRS central chamber measurements compared to the calculated dose outputs for static fields 3 × 3, 2 × 2, 1 × 1 and 0.5 × 0.5 cm2 collimated with MLC whereby jaws are fixed at 3 × 3 cm2 and for static fields shaped with the collimator jaws only (MLC retracted), is on average respectively, 0.2%, 0.8%, 6.8%, 5.7% (6 MV) and 0.1%, 1.3%, 11.7%, 21.6% (10 MV). For the seven brain mets patients was found that the smaller the target volumes, the higher the improvement in agreement between measured and calculated doses after disabling the JTT. Conclusion Fixing the jaws at 3 × 3 cm2 and using the MLC with high positional accuracy to shape the smallest apertures in contrast to the JTT is currently found to be the most accurate treatment technique.

Background and purposePET imaging of cetuximab uptake may help selecting cancer patients with the highest chance of benefit. The aim of this phase I trial was to determine the safety of the tracer 89Zr-cetuximab and to assess tumour uptake.MethodsTwo dose schedules were used; two consecutive doses of 60MBq 89Zr-cetuximab or a single dose of 120MBq, both preceded by 400mg/m2 of unlabelled cetuximab. Toxicity (CTCAE 3.0) was scored twice weekly. PET-CT scans were acquired on days 4, 5 and 6 (step 1) or 5, 6, 7 (step 2). Because tumour uptake could not be assessed satisfactorily, a third step was added including EGFR overexpressing tumours.ResultsNine patients were included (6 NSCLC; 3 HNC). No additional toxicity was associated with administration of 89Zr-cetuximab compared to standard cetuximab. A tumour to blood ratio (TBR)>1 was observed in all but one patient, with a maximum of 4.56. TBR was not different between dose schedules. There was a trend for higher TBR at intervals>5days after injection.ConclusionsBoth presented 89Zr-cetuximab administration schedules are safe. The recommended dose for future trials is 60MBq, with a minimum time interval for scanning of 6days.

Background and purpose: Anatomical changes in non-small cell lung cancer (NSCLC) patients may lead to unacceptable treatment results, requiring adaptive radiotherapy (ART). The method proposed in this study describes the proof-of-principle to automatically select patients eligible for ART.Materials and methods: A method was developed flagging patients potentially requiring replanning using changes in density information between the planning CT and cone-beam CT (CBCT) scan. Potential candidates were defined based on anatomical changes in the primary tumour, mediastinum and a region including the lungs. In total, CBCTs of 70 NSCLC patients were retrospectively scored by two independent experts for the need of replanning using the clinical guidelines. Expert evaluation was used as benchmark for the automatic method and accuracy was quantified using a leave-one-out cross-validation strategy.Results: The automatic method correctly selected 79%, 71%, and 89% of the pre-defined candidates based on anatomical change in the tumour, mediastinum and lungs, respectively. The false positive rate was 27%, 9%, and 19% for these regions, respectively. If a single criterion ('flag') per patient is sufficient for replanning, the overall sensitivity was 89% with a false positive rate of 34%. Most common reasons for false positives were changes in breathing pattern or anatomical shifts outside the evaluated region. Excluding these reasons, the false positive rate dropped to 21% and the accuracy was almost similar to expert evaluation: overall sensitivity of approx. 95% with a false positive rate below 19%.Conclusion: Our method based on daily CBCT allows automatic selection of patients that should be investigated for treatment adaptation. (C) 2017 The Authors. Published by Elsevier Ireland Ltd on behalf of European Society of Radiotherapy & Oncology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).