D. Thorwarth

Geometric analysis of loco-regional recurrences in relation to pre-treatment hypoxia in patients with head and neck cancer

Abstract Introduction: A previous pattern-of-failure study has suggested that up to 50% of the loco-regional failures (LRF) in head and neck squamous cell carcinoma (HNSCC) occur outside the initial hypoxic volume determined by [18F]-fluoromisonidazole-PET ([18F]-FMISO-PET). The aim of the present analysis was to correlate spatial patterns of failure with respect to the pretherapeutic dynamic [18F]-FMISO-PET/CT in HNSCC after radiochemotherapy (RCT). Material and methods: Within a running phase 2 trial using [18F]-FMISO-PET imaging prior to RCT in HNSCC patients (nu2009=u200954), we have observed so far 11 LRF with a minimum follow-up of 12 months. For nine patients, LRF imaging (CT or [18F]-FDG-PET/CT) for pattern-of-failure analysis was available. Analysis included the static 4-h hypoxic subvolume (VH) as well as a M-parameter volume (VM), which is derived from modeling of dynamic PET. Deformable image registration of the CT scan with the recurrent tumor to the pre-treatment [18F]-FMISO-PET/CT and the planning CT was done to quantify the hypoxic subvolumes compared to the recurrent tumor volume. Moreover, a point-of-origin analysis was performed. Results: A total of five local, two regional and two loco-regional recurrences were detected. After deformable image registration of the CT scan with the recurrent tumor to the pre-treatment [18F]-FMISO-PET/CT and the planning CT, a significant overlap of the recurrence volume with [18F]-FMISO-positive subvolumes in the initial gross tumor volume (GTV) was observed. Median overlap of 40.2%, range 9.4–100.0%, for VH and 49.0%, range 4.4–96.4%, for VM was calculated. The point-of-origin analysis showed median distances of 0.0u2009mm, range 0.0–11.3u2009mm to VH and 8.6u2009mm, range 0.0–15.5u2009mm to VM, respectively. Conclusions: Our data suggest that loco-regional recurrences after RCT originate from the initial GTV (primary tumor and/or lymph node metastases) containing hypoxic subvolumes, which supports the concept of hypoxia imaging-based dose escalation.

Distortion correction of diffusion-weighted magnetic resonance imaging of the head and neck in radiotherapy position

guided adaptive radiotherapy in the treatment of lung cancer patients. Acta Oncol. 2015;54:1430–1437. [10] Guckenberger M, Wilbert J, Richter A, et al. Potential of adaptive radiotherapy to escalate the radiation dose in combined radiochemotherapy for locally advanced non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 2011;79:901–908. [11] Korreman S, Rasch C, McNair H, et al. The European Society of Therapeutic Radiology and Oncology-European Institute of Radiotherapy (ESTRO-EIR) report on 3D CT-based in-room image guidance systems: a practical and technical review and guide. Radiother Oncol. 2010;94:129–144. [12] Kwint M, Conijn S, Schaake E, et al. Intra thoracic anatomical changes in lung cancer patients during the course of radiotherapy. Radiother Oncol. 2014;113:392–397. [13] Knap MM, Hoffmann L, Nordsmark M, et al. Daily cone-beam computed tomography used to determine tumour shrinkage and localisation in lung cancer patients. Acta Oncol. 2010;49: 1077–1084. [14] Persoon LC, Egelmeer AG, Ollers MC, et al. First clinical results of adaptive radiotherapy based on 3D portal dosimetry for lung cancer patients with atelectasis treated with volumetricmodulated arc therapy (VMAT). Acta Oncol. 2013;52:1484–1489. [15] Kilburn JM, Soike MH, Lucas JT, et al. Image guided radiation therapy may result in improved local control in locally advanced lung cancer patients. Pract Radiat Oncol. 2016;6:e73–e80. [16] Berkovic P, Paelinck L, Lievens Y, et al. Adaptive radiotherapy for locally advanced non-small cell lung cancer, can we predict when and for whom? Acta Oncol. 2015;54:1438–1444. [17] Derycke S, De Gersem WR, Van Duyse BB, et al. Conformal radiotherapy of Stage III non-small cell lung cancer: a class solution involving non-coplanar intensity-modulated beams. Int J Radiat Oncol Biol Phys. 1998;41:771–777. [18] De Ruysscher D, Faivre-Finn C, Nestle U, et al. European Organisation for Research and Treatment of Cancer recommendations for planning and delivery of high-dose, high-precision radiotherapy for lung cancer. JCO. 2010;28:5301–5310. [19] Shin KE, Chung MJ, Jung MP, et al. Quantitative computed tomographic indexes in diffuse interstitial lung disease: correlation with physiologic tests and computed tomography visual scores. J Comput Assist Tomogr. 2011;35:266–271. [20] Guckenberger M, Richter A, Wilbert J, et al. Adaptive radiotherapy for locally advanced non-small-cell lung cancer does not underdose the microscopic disease and has the potential to increase tumor control. Int J Radiat Oncol Biol Phys. 2011;81: e275–e282. [21] Michienzi A, Kron T, Callahan J, et al. Cone-beam computed tomography for lung cancer – validation with CT and monitoring tumour response during chemo-radiation therapy. J Med Imaging Radiat Oncol. 2017;61:263–270. [22] Juhler-Nøttrup T, Korreman SS, Pedersen AN, et al. Interfractional changes in tumour volume and position during entire radiotherapy courses for lung cancer with respiratory gating and image guidance. Acta Oncol. 2008;47:1406–1413. [23] Pantarotto JR, Piet AHM, Vincent A, et al. Motion analysis of 100 mediastinal lymph nodes: potential pitfalls in treatment planning and adaptive strategies. Int J Radiat Oncol. 2009;74:1092–1099. [24] Weiss E, Robertson SP, Mukhopadhyay N, et al. Tumor, lymph node, and lymph node-to-tumor displacements over a radiotherapy series: analysis of interfraction and intrafraction variations using active breathing control (ABC) in lung cancer. Int J Radiat Oncol Biol Phys. 2012;82:e639–e645. [25] Bosmans G, van Baardwijk A, Dekker A, et al. Time trends in nodal volumes and motion during radiotherapy for patients with stage III non-small-cell lung cancer. Int J Radiat Oncol. 2008;71:139–144. [26] Sonke J-J, Belderbos J. Adaptive radiotherapy for lung cancer. Semin Radiat Oncol. 2010;20:94–106. [27] Chun SG, Hu C, Choy H, et al. Impact of intensity-modulated radiation therapy technique for locally advanced non-small-cell lung cancer: a secondary analysis of the NRG oncology RTOG 0617 randomized clinical trial. J Clin Oncol. 2017;35:56–62. [28] Speirs CK, DeWees TA, Rehman S, et al. Heart dose is an independent dosimetric predictor of overall survival in locally advanced non–small cell lung cancer. J Thorac Oncol. 2017;12:293–301. [29] Jabbour SK, Kim S, Haider SA, et al. Reduction in tumor volume by cone beam computed tomography predicts overall survival in non-small cell lung cancer treated with chemoradiation therapy. Int J Radiat Oncol. 2015;92:627–633.

Overlap of highly FDG-avid and FMISO hypoxic tumor subvolumes in patients with head and neck cancer

Abstract Background: PET imaging may be used to personalize radiotherapy (RT) by identifying radioresistant tumor subvolumes for RT dose escalation. Using the tracers [18F]-fluorodeoxyglucose (FDG) and [18F]-fluoromisonidazole (FMISO), different aspects of tumor biology can be visualized. FDG depicts various biological aspects, e.g., proliferation, glycolysis and hypoxia, while FMISO is more hypoxia specific. In this study, we analyzed size and overlap of volumes based on the two markers for head-and-neck cancer patients (HNSCC). Material and methods: Twenty five HNSCC patients underwent a CT scan, as well as FDG and dynamic FMISO PET/CT prior to definitive radio-chemotherapy in a prospective FMISO dose escalation study. Three PET-based subvolumes of the primary tumor (GTVprim) were segmented: a highly FDG-avid volume VFDG, a hypoxic volume on the static FMISO image acquired four hours post tracer injection (VH) and a retention/perfusion volume (VM) using pharmacokinetic modeling of dynamic FMISO data. Absolute volumes, overlaps and distances to agreement (DTA) were evaluated. Results: Sizes of PET-based volumes and the GTVprim are significantly different (GTVprim>VFDG>VH >VM; pu2009<u2009.05). VH is covered by VFDG or DTAs are small (mean coverage 74.4%, mean DTA 1.4u2009mm). Coverage of VM is less pronounced. With respect to VFDG and VH, the mean coverage is 48.7% and 43.1% and the mean DTA is 5.3u2009mm and 6.3u2009mm, respectively. For two patients, DTAs were larger than 2u2009cm. Conclusions: Hypoxic subvolumes from static PET imaging are typically covered by or in close proximity to highly FDG-avid subvolumes. Therefore, dose escalation to FDG positive subvolumes should cover the static hypoxic subvolumes in most patients, with the disadvantage of larger volumes, resulting in a higher risk of dose-limiting toxicity. Coverage of subvolumes from dynamic FMISO PET is less pronounced. Further studies are needed to explore the relevance of mismatches in functional imaging.

Automatic replanning of VMAT plans for different treatment machines: A template-based approach using constrained optimization

PurposeTo investigate axa0new automatic template-based replanning approach combined with constrained optimization, which may be highly useful for axa0rapid plan transfer for planned or unplanned machine breakdowns. This approach was tested for prostate cancer (PC) and head-and-neck cancer (HNC) cases.MethodsThe constraints of axa0previously optimized volumetric modulated arc therapy (VMAT) plan were used as axa0template for automatic plan reoptimization for different accelerator head models. All plans were generated using the treatment planning system (TPS) Hyperion. Automatic replanning was performed for 16xa0PC cases, initially planned for MLC1 (4u202fmm MLC) and reoptimized for MLC2 (5u202fmm) and MLC3 (10u202fmm) and for 19xa0HNC cases, replanned from MLC2 to MLC3. EUD, Dmean, D2%, and D98% were evaluated for targets; for OARs EUD and D2% were analyzed. Replanning was considered successful if both plans fulfilled equal constraints.ResultsAll prostate cases were successfully replanned. The mean relative target EUD deviation was −0.15% and −0.57% for replanning to MLC2 and MLC3, respectively. OAR sparing was successful in all cases. Replanning of HNC cases from MLC2 to MLC3 was successful in 16/19xa0patients with axa0mean decrease of −0.64% in PTV60 EUD. In three cases target doses were substantially decreased by up to −2.58% (PTV60) and −3.44% (PTV54), respectively. Nevertheless, OAR sparing was always achieved as planned.ConclusionsAutomatic replanning of VMAT plans for axa0different treatment machine by using pre-existing constraints as axa0template for axa0reoptimization is feasible and successful in terms of equal constraints.ZusammenfassungZieleIn dieser Studie wurde ein neuer Template-basierter Ansatz zur automatischen Umplanung von Bestrahlungsplänen mit beschränkter Optimierung untersucht, der für die schnelle Planübertragung im Fall von planmäßigen und außerplanmäßigen Maschinenausfällen von großem Nutzen sein könnte. Der Ansatz wurde für Prostatakarzinom (PK) und Kopf-Hals-Tumor (HNO) Fälle getestet.MethodenDie Beschränkungen eines vorher optimierten Volumetric-modulated-arc-therapy(VMAT)-Plans wurden als Template für die automatische Reoptimierung mit einem anderen Strahlerkopfmodell genutzt. Alle Pläne wurden im Bestrahlungsplanungsprogramm Hyperion erstellt. 16xa0PK-Fälle, die ursprünglich für den Multi-Leaf-Kollimator MLC1 (4u202fmm MLC) geplant waren, wurden automatisch auf MLC2 (5u202fmm) und MLC3 (10u202fmm) umgeplant. Für 19xa0HNO-Fälle erfolgte die Umplanung von MLC2 auf MLC3. Für Zielvolumen (PTV) wurden die „equivalent uniform dose“ (EUD), DMean, D2u202f% und D98u202f% ausgewertet, für Risikoorgane EUD und D2u202f%. Eine Umplanung galt als erfolgreich, wenn beide Pläne gleiche Beschränkungen erfüllten.ErgebnisseAlle PK-Fälle konnten erfolgreich automatisch umgeplant werden. Die mittlere relative Abweichung der PTV EUD betrug −0,15u202fu202f% (MLC2) und −0,57u202f% (MLC3). Die Umplanung von MLC2 auf MLC3 war in 16 von 19xa0HNO-Fällen erfolgreich. Die EUD im PTV60 nahm dabei durchschnittlich um −0,64u202f% ab. In 3xa0Fällen wurden erhebliche Dosiseinbußen von bis zu −2,58u202f% (PTV60) bzw. −3,44u202f% (PTV54) beobachtet. Die Risikoorganschonung konnte jedoch immer wie geplant eingehalten werden.SchlussfolgerungDie automatische Umplanung von VMAT-Plänen für ein anderes Bestrahlungsgerät unter Nutzung eines Templates, automatisch generiert aus den Beschränkungen eines bereits existierenden Plans, ist möglich und erfolgreich im Hinblick auf gleichermaßen erfüllte Beschränkungen.

Assessment of image quality of a radiotherapy-specific hardware solution for PET/MRI in head and neck cancer patients

Background and purpose Functional PET/MRI has great potential to improve radiotherapy planning (RTP). However, data integration requires imaging with radiotherapy-specific patient positioning. Here, we investigated the feasibility and image quality of radiotherapy-customized PET/MRI in head-and-neck cancer (HNC) patients using a dedicated hardware setup. Material and methods Ten HNC patients were examined with simultaneous PET/MRI before treatment, with radiotherapy and diagnostic scan setup, respectively. We tested feasibility of radiotherapy-specific patient positioning and compared the image quality between both setups by pairwise image analysis of 18F-FDG-PET, T1/T2-weighted and diffusion-weighted MRI. For image quality assessment, similarity measures including average symmetric surface distance (ASSD) of PET and MR-based tumor contours, MR signal-to-noise ratio (SNR) and mean apparent diffusion coefficient (ADC) value were used. Results PET/MRI in radiotherapy position was feasible – all patients were successfully examined. ASSD (median/range) of PET and MR contours was 0.6 (0.4–1.2) and 0.9 (0.5–1.3)u202fmm, respectively. For T2-weighted MRI, a reduced SNR of −26.2% (−39.0–−11.7) was observed with radiotherapy setup. No significant difference in mean ADC was found. Conclusions Simultaneous PET/MRI in HNC patients using radiotherapy positioning aids is clinically feasible. Though SNR was reduced, the image quality obtained with a radiotherapy setup meets RTP requirements and the data can thus be used for personalized RTP.

Experimental analysis of correction factors for reference dosimetry in a magnetic field

Abstract Today, hybrid systems of linear accelerator and MRI scanner are clinically available. Therefore it is important to investigate the feasibility of reference dosimetry with ionization chambers in the presence of a magnetic field and determine correction factors. In this work, correction factors under various conditions that influence the chamber response were experimentally investigated, using a conventional 6 MV linear accelerator together with a stand-alone magnet. We found that the correction factor for a PTW31010 ionization chamber ranges from 0.9873 to 1.009 depending on the magnetic field strength, magnetic field orientation and magnetic field size. The phantom material also does have an influence on the measured signal. Therefore, reference dosimetry with ionization chambers in the presence of a magnetic field is feasible, but requires dedicated correction factors, which depend on the experimental setup.

Optimal orientation for ionization chambers in MRgRT reference dosimetry

Abstract The interest in hybrid systems combining magnetic resonance imaging and medical linear accelerator (MR-Linac) is rapidly increasing due to the clinical availability of different systems. Reference dosimetry is a critical issue for integrating these devices into clinical practice. However, the response of ionization chambers changes according to the distinct orientation of the chamber with respect to the magnetic field. In this study, we have carried out Monte Carlo simulations to identify an optimal orientation for thimble type chambers in MRgRT reference dosimetry. Our findings suggest that an orientation where the chamber axis is parallel to the magnetic field axis should be preferred.

EP-1910: Evaluation of diffusion-weighted imaging properties of a RT-specific positioning solution for PET/MR

Purpose or Objective: A Varian TrueBeam with OBI was commissioned in 2014. During early clinical use concerns were raised regarding thoracic CBCT image quality in comparison with that observed in Elekta XVI images. Streaking artefacts caused by respiratory motion were the primary reason for the perceived poor quality. This study compared the image quality of the TrueBeam OBI with the other CBCT systems at the centre, a Varian Trilogy OBI and Elekta XVI, using quantitative and qualitative methods.

PO-0923: Comparing FMISO and FDG positive tumour sub-volumes for PET-based dose escalation in SCCHN

Conclusion: For 26% of the radiomics features there is good agreement between CT1 and CBCT. 81% of the image features show high correlation between CBCT-FX1 and CBCTFX2 where no large differences are expected. In the future, radiomic features derived from CBCT images will be investigated to monitor changes of CBCT features over the course of treatment. One has to be careful with mixing radiomic features derived on planning CT and CBCT scans.

PD-0458: Estimation of the robustness of hypoxia PET quantification for multicenter data comparison

Conclusions: A stoichiometric calibration is feasible using all three parameterizations. The resulting mean-calibration curves are similar for all three methods. However, when introducing a random variation in the measured CT-numbers, as is manifest daily from scan to scan, the parameterization using 3 fitting parameters demonstrates significantly larger variation in the calculated CT-numbers of the theoretical tissues. The impact of this to the uncertainty in the proton ranges in human tissues will be studied further.