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Background: Systematic mediastinal lymph node staging by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) improves accuracy of staging in patients with early-stage non-small-cell lung cancer (NSCLC). However, patients with locally advanced NSCLC commonly undergo only selective lymph node sampling. This study aimed to determine the proportion of patients with locally advanced NSCLC in whom systematic endoscopic mediastinal staging identified PET-occult lymph node metastases, and to describe the consequences of PET-occult disease on radiotherapy planning., Methods: This prospective, international, multicentre, single-arm, international study was conducted at seven tertiary lung cancer centres in four countries (Australia, Canada, the Netherlands, and the USA). Patients aged 18 years or older with suspected or known locally advanced NSCLC underwent systematic endoscopic mediastinal lymph node staging before combination chemoradiotherapy or high-dose palliative radiotherapy. The primary endpoint was the proportion of participants with PET-occult mediastinal lymph node metastases shown following systematic endoscopic staging. The study was prospectively registered with Australian New Zealand Clinical Trials Registry, ACTRN12617000333314., Findings: From Jan 30, 2018, to March 23, 2022, 155 patients underwent systematic endoscopic mediastinal lymph node staging and were eligible for analysis. 58 (37%) of patients were female and 97 (63%) were male. Discrepancy in extent of mediastinal disease identified by PET and EBUS-TBNA was observed in 57 (37% [95% CI 29-44]) patients. PET-occult lymph node metastases were identified in 18 (12% [7-17]) participants, including 16 (13% [7-19]) of 123 participants with clinical stage IIIA or cN2 NSCLC. Contralateral PET-occult N3 disease was identified in nine (7% [2-12]) of 128 participants staged cN0, cN1, or cN2. Identification of PET-occult disease resulted in clinically significant changes to treatment in all 18 patients. In silico dosimetry studies showed the median volume of PET-occult lymph nodes receiving the prescription dose of 60 Gy was only 10·1% (IQR 0·1-52·3). No serious adverse events following endoscopic staging were reported., Interpretation: Our findings suggests that systematic endoscopic mediastinal staging in patients with locally advanced or unresectable NSCLC is more accurate than PET alone in defining extent of mediastinal involvement. Standard guideline-recommended PET-based radiotherapy planning results in suboptimal tumour coverage. Our findings indicate that systematic endoscopic staging should be routinely performed in patients with locally advanced NSCLC being considered for radiotherapy to accurately inform radiation planning and treatment decision making in patients with locally advanced NSCLC., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Radiation therapy treatment for non-small cell lung cancer (NSCLC) may result in radiation damage to the perfused lung. The loss in perfusion may be measured from positron tomography emission (PET) perfusion imaging; however, this modality may not be widely available. Dual-energy computed tomography (DECT) with contrast may be an alternative to PET/CT. The purpose of this work is to investigate the equivalence of dose-response curves (DRCs) determined from PET and DECT in NSCLC., Methods and Materials: PET and DECT data sets from the prospective clinical trial HI-FIVE (NTC03569072) were included in this preplanned trial analysis. Patients underwent 68 Ga-macroaggregated albumin PET/CT examination and DECT with contrast on the same day at baseline and at 3 and 12 months after treatment. The perfused lung was defined from a threshold based on the maximum standardized uptake value (%SUVmax)/iodine concentration (%IoMax) in PET/DECT. The equivalence between PET and DECT DRC was established by comparing (1) the average of the normalized overlap of the 2 DRCs ranging from 0 (no overlap) to 1 (perfect overlap) and (2) the slope of a linear model applied to DRCs., Results: Of the 19 patients enrolled in the clinical trial, 14/10 patients had a posttreatment imaging session at a median of 4.5/13.5 months, respectively. With 30%SUVmax/35%IoMax, the average normalized overlap was maximized, and the difference between PET and DECT slopes of the linear model was minimized at each time point (slope = 0.76%/Gy / 0.75%/Gy at 3 months and 0.86%/Gy / 0.87%/Gy at 12 months determined from PET/DECT)., Conclusions: The dose-response relationship determined from DECT was comparable to that from PET at 3 and 12 months after treatment in patients with NSCLC., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The TROG 09.02 CHISEL trial compared conventional radiation therapy (CRT) with stereotactic body radiation therapy (SBRT) in patients with inoperable early-stage non-small cell lung cancer. Patients randomized to SBRT had less local failure and improved overall survival. This analysis reports differences in pulmonary function tests (PFTs) and the 6-minute walk test (SMWT) between patients who received SBRT and those who received CRT., Methods and Materials: We analyzed the PFTs and SMWTs of all patients recruited to the CHISEL [trial. During this trial, patients underwent serial PFTs. Linear regression models were used to compare parameters between SBRT and CRT at 3 and 12 months after treatment., Results: One hundred and one patients were enrolled; 33 patients were treated with CRT, 61 were treated with SBRT, and 7 did not receive treatment. Primary tumor size was similar between arms: SBRT 25 mm (standard deviation [SD], 9) and CRT 28 mm (SD, 9). On regression analysis, at 3 and 12 months, there was no evidence of a difference between arms in PFT decline or distance walked in the SMWT. Planning target volume size was significantly larger in the CRT arm, 142.79 cc (SD, 61.14), compared with the SBRT group, 46.15 cc (SD, 23.39). The mean biologically effective dose received by the target was significantly larger in the SBRT group, 125.92 Gy (SD, 21.58), compared with CRT, 65.49 Gy (SD, 6.32). Mean dose to the lungs minus the gross target volume incorporating motion was 8.9 Gy (SD, 2.34) in the CRT group and 4.37 Gy (SD, 1.42) in the SBRT group., Conclusions: Despite the considerably higher biologically effective doses delivered to the tumor in SBRT, there was no difference in decline in respiratory function observed between the 2 groups., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective. Functional lung avoidance (FLA) radiotherapy treatment aims to spare lung regions identified as functional from imaging. Perfusion contributes to lung function and can be measured from the determination of pulmonary blood volume (PBV). An advantageous alternative to the current determination of PBV from positron emission tomography (PET) may be from dual energy CT (DECT), due to shorter examination time and widespread availability. This study aims to determine the correlation between PBV determined from DECT and PET in the context of FLA radiotherapy. Approach. DECT and PET acquisitions at baseline of patients enrolled in the HI-FIVE clinical trial (ID: NCT03569072) were reviewed. Determination of PBV from PET imaging (PBVPET), from DECT imaging generated from a commercial software (Syngo.via, Siemens Healthineers, Forchheim, Germany) with its lowest (PBVsyngoR=1) and highest (PBVsyngoR=10) smoothing level parameter value ( R ), and from a two-material decomposition (TMD) method (PBVTMDL) with variable median filter kernel size ( L ) were compared. Deformable image registration between DECT images and the CT component of the PET/CT was applied to PBV maps before resampling to the PET resolution. The Spearman correlation coefficient ( r s ) between PBV determinations was calculated voxel-wise in lung subvolumes. Main results. Of this cohort of 19 patients, 17 had a DECT acquisition at baseline. PBV maps determined from the commercial software and the TMD method were very strongly correlated [ r s (PBVsyngoR=1,PBVTMDL=1) = 0.94 ± 0.01 and r s (PBVsyngoR=10,PBVTMDL=9) = 0.94 ± 0.02].PBVPETwas strongly correlated withPBVTMDL[ r s (PBVPET,PBVTMDL=28) = 0.67 ± 0.11]. Perfusion patterns differed along the posterior-anterior direction [ r s (PBVPET,PBVTMDL=28) = 0.77 ± 0.13/0.57 ± 0.16 in the anterior/posterior region]. Significance . A strong correlation between DECT and PET determination of PBV was observed. Streak and smoothing effects in DECT and gravitational artefacts and misregistration in PET reduced the correlation posteriorly., (© 2023 Institute of Physics and Engineering in Medicine.)

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is established as the preferred method of mediastinal lymph node (LN) staging in non-small cell lung cancer (NSCLC). Selective (targeted) LN sampling is most commonly performed however studies in early stage NSCLC and locally advanced NSCLC confirm systematic EBUS-TBNA evaluation improves accuracy of mediastinal staging. This study aims to establish the rate of detection of positron emission tomography (PET)-occult LN metastases following systematic LN staging by EBUS-TBNA, and to determine the utility of systematic mediastinal staging for accurate delineation of radiation treatment fields in patients with locally advanced NSCLC., Methods: Consecutive patients undergoing EBUS-TBNA for diagnosis/staging of locally advanced NSCLC will be enrolled in this international multi-centre single arm study. Systematic mediastinal LN evaluation will be performed, with all LN exceeding 6 mm to be sampled by TBNA. Where feasible, endoscopic ultrasound staging (EUS-B) may also be performed. Results of minimally invasive staging will be compared to FDG-PET. The primary end-point is proportion of patients in whom systematic LN staging identified PET-occult NSCLC metastases. Secondary outcome measures include (i) rate of nodal upstaging, (ii) false positive rate of PET for mediastinal LN assessment, (iii) analysis of clinicoradiologic risk factors for presence of PET-occult LN metastases, (iv) impact of systematic LN staging in patients with discrepant findings on PET and EBUS-TBNA on target coverage and dose to organs at risk (OAR) in patients undergoing radiotherapy., Discussion: With specificity of PET of 90%, guidelines recommend tissue confirmation of positive mediastinal LN to ensure potentially early stage patients are not erroneously denied potentially curative resection. However, while confirmation of pathologic LN is routinely sought, the exact extent of mediastinal LN involvement in NSCLC in patient with Stage III NSCLC is rarely established. Studies examining systematic LN staging in early stage NSCLC report a significant discordance between PET and EBUS-TBNA. In patients with locally advanced disease this has significant implications for radiation field planning, with risk of geographic miss in the event of PET-occult mediastinal LN metastases. The SEISMIC study will examine both diagnostic outcomes following systematic LN staging with EBUS-TBNA, and impact on radiation treatment planning., Trial Registration: ACTRN12617000333314, ANZCTR, Registered on 3 March 2017., (© 2022. The Author(s).)

Stereotactic ablative radiotherapy (SABR) is a well-established treatment for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) and pulmonary oligometastases. The use of single-fraction SABR in this setting is supported by excellent local control and safety profiles which appear equivalent to multi-fraction SABR based on the available data. The resource efficiency and reduction in hospital outpatient visits associated with single-fraction SABR have been particularly advantageous during the COVID-19 pandemic. Despite the increased interest, single-fraction SABR in subgroups of patients remains controversial, including those with centrally located tumours, synchronous targets, proximity to dose-limiting organs at risk, and concomitant severe respiratory illness. This review provides an overview of the published randomised evidence evaluating single-fraction SABR in primary lung cancer and pulmonary oligometastases, the common clinical challenges faced, immunogenic effect of SABR, as well as technical and cost-utility considerations., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Artificial intelligence and radiomics have the potential to revolutionise cancer prognostication and personalised treatment. Manual outlining of the tumour volume for extraction of radiomics features (RF) is a subjective process. This study investigates robustness of RF to inter-observer variation (IOV) in contouring in lung cancer. We utilised two public imaging datasets: 'NSCLC-Radiomics' and 'NSCLC-Radiomics-Interobserver1' ('Interobserver'). For 'NSCLC-Radiomics', we created an additional set of manual contours for 92 patients, and for 'Interobserver', there were five manual and five semi-automated contours available for 20 patients. Dice coefficients (DC) were calculated for contours. 1113 RF were extracted including shape, first order and texture features. Intraclass correlation coefficient (ICC) was computed to assess robustness of RF to IOV. Cox regression analysis for overall survival (OS) was performed with a previously published radiomics signature. The median DC ranged from 0.81 ('NSCLC-Radiomics') to 0.85 ('Interobserver'-semi-automated). The median ICC for the 'NSCLC-Radiomics', 'Interobserver' (manual) and 'Interobserver' (semi-automated) were 0.90, 0.88 and 0.93 respectively. The ICC varied by feature type and was lower for first order and gray level co-occurrence matrix (GLCM) features. Shape features had a lower median ICC in the 'NSCLC-Radiomics' dataset compared to the 'Interobserver' dataset. Survival analysis showed similar separation of curves for three of four RF apart from 'original_shape_Compactness2', a feature with low ICC (0.61). The majority of RF are robust to IOV, with first order, GLCM and shape features being the least robust. Semi-automated contouring improves feature stability. Decreased robustness of a feature is significant as it may impact upon the features' prognostic capability., (© 2022. Crown.)

Background and Purpose: Radiomics allows extraction of quantifiable features from imaging. This study performs a systematic review and meta-analysis of the performance of radiomics based prognostic models in non-small cell lung cancer (NSCLC)., Materials and Methods: A literature review was performed following PRISMA guidelines. Medline, EMBASE and Cochrane databases were searched for articles investigating radiomics features predictive of overall survival (OS) in NSCLC treated with curative intent radiotherapy. A random-effects meta-analysis of Harrell's Concordance Index (C-index) was performed on the performance of radiomics models., Results: Of the 2746 articles retrieved, 40 studies of 55 datasets and 6223 patients were eligible for inclusion in the systematic review. There was significant heterogeneity in the methodology for feature selection and model development. Twelve datasets reported the C-index of radiomics based models in predicting OS and were included in the meta-analysis. The C-index random effects estimate was 0.57 (95% CI 0.53-0.62). There was significant heterogeneity (I 2  = 70.3%)., Conclusions: Based on this review, radiomics based models for lung cancer have to date demonstrated modest prognostic capabilities. Future research should consider using standardised radiomics features, robust feature selection and model development, and deep learning techniques, absolving the need for pre-defined features, to improve imaging-based models., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Purpose: The purpose of this work is to present the clinical experience from the first-in-human trial of real-time tumor targeting via MLC tracking for stereotactic ablative body radiotherapy (SABR) of lung lesions., Methods and Materials: Seventeen patients with stage 1 non-small cell lung cancer (NSCLC) or lung metastases were included in a study of electromagnetic transponder-guided MLC tracking for SABR (NCT02514512). Patients had electromagnetic transponders inserted near the tumor. An MLC tracking SABR plan was generated with planning target volume (PTV) expanded 5 mm from the end-exhale gross tumor volume (GTV). A clinically approved comparator plan was generated with PTV expanded 5 mm from a 4DCT-derived internal target volume (ITV). Treatment was delivered using a standard linear accelerator to continuously adapt the MLC based on transponder motion. Treated volumes and reconstructed delivered dose were compared between MLC tracking and comparator ITV-based treatment., Results: All seventeen patients were successfully treated with MLC tracking (70 successful fractions). MLC tracking treatment delivery time averaged 8 minutes. The time from the start of CBCT to the end of treatment averaged 22 minutes. The MLC tracking PTV for 16/17 patients was smaller than the ITV-based PTV (range -1.6% to 44% reduction, or -0.6 to 18 cc). Reductions in mean lung dose (27 cGy) and V20Gy (50 cc) were statistically significant (p < 0.02). Reconstruction of treatment doses confirmed a statistically significant improvement in delivered GTV D98% (p < 0.05) from planned dose compared with the ITV-based plans., Conclusion: The first treatments with lung MLC tracking have been successfully performed in seventeen SABR patients. MLC tracking for lung SABR is feasible, efficient and delivers high-precision target dose and lower normal tissue dose., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: In the curative-intent treatment of locally advanced lung cancer, significant morbidity and mortality can result from thoracic radiation therapy. Symptomatic radiation pneumonitis occurs in one in three patients and can lead to radiation-induced fibrosis. Local failure occurs in one in three patients due to the lungs being a dose-limiting organ, conventionally restricting tumour doses to around 60 Gy. Functional lung imaging using positron emission tomography (PET)/CT provides a geographic map of regional lung function and preclinical studies suggest this enables personalised lung radiotherapy. This map of lung function can be integrated into Volumetric Modulated Arc Therapy (VMAT) radiotherapy planning systems, enabling conformal avoidance of highly functioning regions of lung, thereby facilitating increased doses to tumour while reducing normal tissue doses., Methods and Analysis: This prospective interventional study will investigate the use of ventilation and perfusion PET/CT to identify highly functioning lung volumes and avoidance of these using VMAT planning. This single-arm trial will be conducted across two large public teaching hospitals in Australia. Twenty patients with stage III non-small cell lung cancer will be recruited. All patients enrolled will receive dose-escalated (69 Gy) functional avoidance radiation therapy. The primary endpoint is feasibility with this achieved if ≥15 out of 20 patients meet pre-defined feasibility criteria. Patients will be followed for 12 months post-treatment with serial imaging, biomarkers, toxicity assessment and quality of life assessment., Discussion: Using advanced techniques such as VMAT functionally adapted radiation therapy may enable safe moderate dose escalation with an aim of improving local control and concurrently decreasing treatment related toxicity. If this technique is proven feasible, it will inform the design of a prospective randomised trial to assess the clinical benefits of functional lung avoidance radiation therapy., Ethics and Dissemination: This study was approved by the Peter MacCallum Human Research Ethics Committee. All participants will provide written informed consent. Results will be disseminated via publications., Trials Registration Number: NCT03569072; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Advanced imaging techniques allow functional information to be derived and integrated into treatment planning., Methods: A systematic review was conducted with the primary objective to evaluate the ability of functional lung imaging to predict risk of radiation pneumonitis. Secondary objectives were to evaluate dose-response relationships on post treatment functional imaging and assess the utility in including functional lung information into treatment planning. A structured search for publications was performed following PRISMA guidelines and registered on PROSPERO., Results: 814 articles were screened against review criteria and 114 publications met criteria. Methods of identifying functional lung included using CT, MRI, SPECT and PET to image ventilation or perfusion. Six studies compared differences between functional and anatomical lung imaging at predicting radiation pneumonitis. These found higher predictive values using functional lung imaging. Twenty-one studies identified a dose-response relationship on post-treatment functional lung imaging. Nineteen planning studies demonstrated the ability of functional lung optimised planning techniques to spare regions of functional lung. Meta-analysis of these studies found that mean (95% CI) functional volume receiving 20 Gy was reduced by 4.2% [95% CI: 2.3: 6.0] and mean lung dose by 2.2 Gy [95% CI: 1.2: 3.3] when plans were optimised to spare functional lung. There was significant variation between publications in the definition of functional lung., Conclusion: Functional lung imaging may have potential utility in radiation therapy planning and delivery, although significant heterogeneity was identified in approaches and reporting. Recommendations have been made based on the available evidence for future functional lung trials., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Background: Ga-68-macroaggregated albumin ((68)Ga-perfusion) positron emission tomography/computed tomography (PET/CT) is a novel imaging technique for the assessment of functional lung volumes. The purpose of this study was to use this imaging technique for functional adaptation of definitive radiotherapy plans in patients with non-small cell lung cancer (NSCLC)., Methods: This was a prospective clinical trial of patients with NSCLC who received definitive 3-dimensional (3D) conformal radiotherapy to 60 Gy in 30 fx and underwent pretreatment respiratory-gated (4-dimensional [4D]) perfusion PET/CT. The "perfused" lung volume was defined as all lung parenchyma taking up radiotracer, and the "well-perfused" lung volume was contoured using a visually adapted threshold of 30% maximum standardized uptake value (SUV max). Alternate 3D conformal plans were subsequently created and optimized to avoid perfused and well-perfused lung volumes. Functional dose volumetrics were compared using mean lung dose (MLD), V5 (volume receiving 5 Gy or more), V10, V20, V30, V40, V50, and V60 parameters., Results: Fourteen consecutive patients had alternate radiotherapy plans created based on functional lung volumes. When considering the original treatment plan, the dose to perfused and well-perfused functional lung volumes was similar to that of the conventional anatomical lung volumes with an average MLD of 12.15, 12.67, and 12.11 Gy, respectively. Plans optimized for well-perfused lung improved functional V30, V40, V50, and V60 metrics (all P values <.05). The functional MLD of well-perfused lung was improved by a median of 0.86 Gy, P < .01. However, plans optimized for perfused lung only showed significant improvement in the functional V60 dose parameter (median 1.00%, P = .04) but at a detriment of a worse functional V5 (median 3.33%, P = .05)., Conclusions: This study demonstrates proof of principle that 4D-perfusion PET/CT may enable functional lung avoidance during treatment planning of patients with NSCLC. Radiotherapy plans adapted to well-perfused but not perfused functional lung volumes allow for reduction in dose to functional lung using 3D conformal radiotherapy., (© The Author(s) 2015.)

Purpose: To investigate (68)Ga-ventilation/perfusion (V/Q) positron emission tomography (PET)/computed tomography (CT) as a novel imaging modality for assessment of perfusion, ventilation, and lung density changes in the context of radiation therapy (RT)., Methods and Materials: In a prospective clinical trial, 20 patients underwent 4-dimensional (4D)-V/Q PET/CT before, midway through, and 3 months after definitive lung RT. Eligible patients were prescribed 60 Gy in 30 fractions with or without concurrent chemotherapy. Functional images were registered to the RT planning 4D-CT, and isodose volumes were averaged into 10-Gy bins. Within each dose bin, relative loss in standardized uptake value (SUV) was recorded for ventilation and perfusion, and loss in air-filled fraction was recorded to assess RT-induced lung fibrosis. A dose-effect relationship was described using both linear and 2-parameter logistic fit models, and goodness of fit was assessed with Akaike Information Criterion (AIC)., Results: A total of 179 imaging datasets were available for analysis (1 scan was unrecoverable). An almost perfectly linear negative dose-response relationship was observed for perfusion and air-filled fraction (r(2)=0.99, P<.01), with ventilation strongly negatively linear (r(2)=0.95, P<.01). Logistic models did not provide a better fit as evaluated by AIC. Perfusion, ventilation, and the air-filled fraction decreased 0.75 ± 0.03%, 0.71 ± 0.06%, and 0.49 ± 0.02%/Gy, respectively. Within high-dose regions, higher baseline perfusion SUV was associated with greater rate of loss. At 50 Gy and 60 Gy, the rate of loss was 1.35% (P=.07) and 1.73% (P=.05) per SUV, respectively. Of 8/20 patients with peritumoral reperfusion/reventilation during treatment, 7/8 did not sustain this effect after treatment., Conclusions: Radiation-induced regional lung functional deficits occur in a dose-dependent manner and can be estimated by simple linear models with 4D-V/Q PET/CT imaging. These findings may inform future studies of functional lung avoidance using V/Q PET/CT., (Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.)

Purpose: Measuring changes in lung perfusion resulting from radiation therapy dose requires registration of the functional imaging to the radiation therapy treatment planning scan. This study investigates registration accuracy and utility for positron emission tomography (PET)/computed tomography (CT) perfusion imaging in radiation therapy for non-small cell lung cancer., Methods: (68)Ga 4-dimensional PET/CT ventilation-perfusion imaging was performed before, during, and after radiation therapy for 5 patients. Rigid registration and deformable image registration (DIR) using B-splines and Demons algorithms was performed with the CT data to obtain a deformation map between the functional images and planning CT. Contour propagation accuracy and correspondence of anatomic features were used to assess registration accuracy. Wilcoxon signed-rank test was used to determine statistical significance. Changes in lung perfusion resulting from radiation therapy dose were calculated for each registration method for each patient and averaged over all patients., Results: With B-splines/Demons DIR, median distance to agreement between lung contours reduced modestly by 0.9/1.1 mm, 1.3/1.6 mm, and 1.3/1.6 mm for pretreatment, midtreatment, and posttreatment (P < .01 for all), and median Dice score between lung contours improved by 0.04/0.04, 0.05/0.05, and 0.05/0.05 for pretreatment, midtreatment, and posttreatment (P < .001 for all). Distance between anatomic features reduced with DIR by median 2.5 mm and 2.8 for pretreatment and midtreatment time points, respectively (P = .001) and 1.4 mm for posttreatment (P > .2). Poorer posttreatment results were likely caused by posttreatment pneumonitis and tumor regression. Up to 80% standardized uptake value loss in perfusion scans was observed. There was limited change in the loss in lung perfusion between registration methods; however, Demons resulted in larger interpatient variation compared with rigid and B-splines registration., Conclusions: DIR accuracy in the data sets studied was variable depending on anatomic changes resulting from radiation therapy; caution must be exercised when using DIR in regions of low contrast or radiation pneumonitis. Lung perfusion reduces with increasing radiation therapy dose; however, DIR did not translate into significant changes in dose-response assessment., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background and Purpose: To assess the utility of functional lung avoidance using IMRT informed by four-dimensional (4D) ventilation/perfusion (V/Q) PET/CT., Materials and Methods: In a prospective clinical trial, patients with non-small cell lung cancer (NSCLC) underwent 4D-V/Q PET/CT scanning before 60Gy of definitive chemoradiation. Both "highly perfused" (HPLung) and "highly ventilated" (HVLung) lung volumes were delineated using a 70th centile SUV threshold, and a "ventilated lung volume" (VLung) was created using a 50th centile SUV threshold. For each patient four IMRT plans were created, optimised to the anatomical lung, HPLung, HVLung and VLung volumes, respectively. Improvements in functional dose volumetrics when optimising to functional volumes were assessed using mean lung dose (MLD), V5, V10, V20, V30, V40, V50 and V60 parameters., Results: The study cohort consisted of 20 patients with 80 IMRT plans. Plans optimised to HPLung resulted in a significant reduction of functional MLD by a mean of 13.0% (1.7Gy), p=0.02. Functional V5, V10 and V20 were improved by 13.2%, 7.3% and 3.8% respectively (p-values<0.04). There was no significant sparing of dose to functional lung when adapting to VLung or HVLung. Plan quality was highly consistent with a mean PTV D95 and D5 ranging from 60.8Gy to 61.0Gy and 63.4Gy to 64.5Gy, respectively, and mean conformity and heterogeneity index ranging from 1.11 to 1.17 and 0.94 to 0.95, respectively., Conclusion: IMRT plans adapted to perfused but not ventilated lung on 4D-V/Q PET/CT allowed for reduced dose to functional lung whilst maintaining consistent plan quality., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Deformable image registration (DIR) is an attractive method for automatic propagation of regions of interest (ROIs) in adaptive lung radiotherapy. This study investigates DIR for automatic contour propagation in adaptive Non Small Cell Lung Carcinoma patients., Methods: Pre and mid-treatment fan beam 4D-kVCT scans were taken for 17 NSCLC patients. Gross tumour volumes (GTV), nodal-GTVs, lungs, esophagus and spinal cord were delineated on all kVCT scans. ROIs were propagated from pre- to mid-treatment images using three DIR algorithms. DIR-propagated ROIs were compared with physician-drawn ROIs on the mid-treatment scan using the Dice score and the mean slicewise Hausdorff distance to agreement (MSHD). A physician scored the DIR-propagated ROIs based on clinical utility., Results: Good agreement between the DIR-propagated and physician drawn ROIs was observed for the lungs and spinal cord. Agreement was not as good for the nodal-GTVs and esophagus, due to poor soft-tissue contrast surrounding these structures. 96% of OARs and 85% of target volumes were scored as requiring no or minor adjustments., Conclusions: DIR has been shown to be a clinically useful method for automatic contour propagation in adaptive radiotherapy however thorough assessment of propagated ROIs by the treating physician is recommended.