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The use of stereotactic ablative radiotherapy (SABR) for central lung tumors is increasing. Centrally located lung tumors can be subdivided into two categories, namely the ‘moderately central’ tumors where the planning target volume is located within 2 cm of the proximal bronchial tree, and the ‘ultracentral’ tumors where a planning target volume (PTV) overlaps the trachea or main stem bronchi. The toxicity of SABR appears acceptable when ‘moderately central’ tumors are treated using techniques that comply with organs at risk tolerance doses used for prospective trials and in recent publications. A high toxicity is seen when ultracentral tumors are treated using SABR, and conventional radiotherapy appears more appropriate in such tumors as the true normal organ tolerance doses remain unknown. When ultracentral tumors are treated with non-SABR hypofractionated radiotherapy, a homogenous dose distribution in the planning target volume and limitation of both normal organ maximum point doses and volumes receiving high doses seems to be needed.

PURPOSE: To investigate, in the setting of stereotactic ablative radiation therapy (SABR) for early-stage non-small cell lung cancer, the incidence and patterns of change in high-risk radiologic features (HRFs) in patients known to have no local recurrence.METHODS AND MATERIALS: Computed tomography (CT) scans of patients treated using volumetric modulated arc therapy SABR between 2008 and 2013 were eligible if follow-up scans were available for 2 years and no local recurrences were diagnosed. All scans were reviewed at a workstation using an add-on tool for ClearCanvas (Synaptive Medical). Five clinicians who were blinded to clinical outcomes scored the presence of HRFs: enlarging opacity (EO), sequential enlarging opacity, enlarging opacity after 12 months (EO12), bulging margin, loss of linear margins, cranio-caudal growth, and loss of air bronchogram. After each review, clinicians recommended follow-up procedures based on published recommendations.RESULTS: A total of 88 patients (747 CT scans) were evaluated. The HRFs most frequently recorded by ≥3 observers on at least 1 follow-up scan were EO (64.8%), EO12 (50.0%), and sequential enlarging opacity (13.6%). Fifty-six patients developed EO within the first year after SABR, and of these, 46 also developed subsequent EO (EO12). In 76 patients who developed EO after 1 year of follow-up, 30 had not manifested EO previously. Three or more HRFs have been associated with recurrences, and this was observed on CT scan in 22.7% of patients. In their routine care, 6 patients had undergone a positron emission tomography scan because of a suspected local recurrence, and 4 underwent an attempt at biopsy.CONCLUSIONS: More than 50% of patients without a local recurrence after SABR develop HRFs. Because ≥3 HRFs were present in nearly 25% of patients, further refinement of follow-up recommendations are necessary.

Purpose: To investigate the incorporation of pretherapy regional ventilation function in predicting radiation fibrosis (RF) in stage III nonsmall cell lung cancer (NSCLC) patients treated with concurrent thoracic chemoradiotherapy. Methods: Thirty-seven patients with stage III NSCLC were retrospectively studied. Patients received one cycle of cisplatin–gemcitabine, followed by two to three cycles of cisplatin–etoposide concurrently with involved-field thoracic radiotherapy (46–66 Gy; 2 Gy/fraction). Pretherapy regional ventilation images of the lung were derived from 4D computed tomography via a density change–based algorithm with mass correction. In addition to the conventional dose–volume metrics (V 20, V 30, V 40, and mean lung dose), dose–function metrics (fV20, fV30, fV40, and functional mean lung dose) were generated by combining regional ventilation and radiation dose. A new class of metrics was derived and referred to as dose–subvolume metrics (sV20, sV30, sV40, and subvolume mean lung dose); these were defined as the conventional dose–volume metrics computed on the functional lung. Area under the receiver operating characteristic curve (AUC) values and logistic regression analyses were used to evaluate these metrics in predicting hallmark characteristics of RF (lung consolidation, volume loss, and airway dilation). Results: AUC values for the dose–volume metrics in predicting lung consolidation, volume loss, and airway dilation were 0.65–0.69, 0.57–0.70, and 0.69–0.76, respectively. The respective ranges for dose–function metrics were 0.63–0.66, 0.61–0.71, and 0.72–0.80 and for dose–subvolume metrics were 0.50–0.65, 0.65–0.75, and 0.73–0.85. Using an AUC value = 0.70 as cutoff value suggested that at least one of each type of metrics (dose–volume, dose–function, dose–subvolume) was predictive for volume loss and airway dilation, whereas lung consolidation cannot be accurately predicted by any of the metrics. Logistic regression analyses showed that dose–function and dose–subvolume metrics were significant (P values ≤ 0.02) in predicting volume airway dilation. Likelihood ratio test showed that when combining dose–function and/or dose–subvolume metrics with dose–volume metrics, the achieved improvements of prediction accuracy on volume loss and airway dilation were significant (P values ≤ 0.04). Conclusions: The authors’ results demonstrated that the inclusion of regional ventilation function improved accuracy in predicting RF. In particular, dose–subvolume metrics provided a promising method for preventing radiation-induced pulmonary complications.

Volumetric response to therapy has been suggested as a biomarker for patient-centered outcomes. The primary aim of this pilot study was to investigate whether the volumetric response to induction chemoradiotherapy was associated with pathological complete response (pCR) or survival in patients with superior sulcus tumors managed with trimodality therapy. The secondary aim was to evaluate a semiautomated method for serial volume assessment.In this retrospective study, treatment outcomes were obtained from a departmental database. The tumor was delineated on the computed tomography (CT) scan used for radiotherapy planning, which was typically performed during the first cycle of chemotherapy. These contours were transferred to the post-chemoradiotherapy diagnostic CT scan using deformable image registration (DIR) with/without manual editing.CT scans from 30 eligible patients were analyzed. Median follow-up was 51 months. Neither absolute nor relative reduction in tumor volume following chemoradiotherapy correlated with pCR or 2-year survival. The tumor volumes determined by DIR alone and DIR + manual editing correlated to a high degree (R(2) = 0.99, P 0.01).Volumetric response to induction chemoradiotherapy was not correlated with pCR or survival in patients with superior sulcus tumors managed with trimodality therapy. DIR-based contour propagation merits further evaluation as a tool for serial volumetric assessment.

Radiological pneumonitis and fibrosis are common after stereotactic body radiotherapy (SBRT) but current scoring systems are qualitative and subjective. We evaluated the use of CT density measurements and a deformable registration tool to quantitatively measure lung changes post-SBRT. Material and methods. Four-dimensional CT datasets from 25 patients were imported into an image analysis program. Deformable registration was done using a B-spline algorithm (VelocityAI) and evaluated by landmark matching. The effects of respiration, contrast, and CT scanner on density measurements were evaluated. The relationship between density and clinician-scored radiological pneumonitis was assessed. Results. Deformable registration resulted in more accurate image matching than rigid registration. CT lung density was maximal at end-expiration, and most deformation with breathing occurred in the lower thorax. Use of contrast increased mean lung density by 18 HU (range 16-20 HU; p = 0.004). Diagnostic scans had a lower mean lung density than planning scans (mean difference 57 HU in lung contralateral to tumor; p = 0.048). Post-treatment CT density measurements correlated strongly with clinician-scored radiological pneumonitis (r = 0.75; p < 0.001). Conclusions. Quantitative analysis of changes in lung density correlated strongly with physician-assigned radiologic pneumonitis scores. Deformable registration and CT density measurements permit objective assessment of treatment toxicity.

Purpose: To investigate the incorporation of pre-therapy regional ventilation function in predicting radiation fibrosis (RF) in stage III non-small-cell lung cancer (NSCLC) patients treated with concurrent thoracic chemoradiotherapy. Methods: 37 stage III NSCLC patients were retrospectively studied. Patients received one cycle of cisplatin-gemcitabine, followed by two to three cycles of cisplatin-etoposide concurrently with involved-field thoracic radiotherapy between 46 and 66 Gy (2 Gy per fraction). Pre-therapy regional ventilation images of the lung were derived from 4DCT via a density-change-based image registration algorithm with mass correction. RF was evaluated at 6-months post-treatment using radiographic scoring based on airway dilation and volume loss. Three types of ipsilateral lung metrics were studied: (1) conventional dose-volume metrics (V20, V30, V40, and mean-lung-dose (MLD)), (2) dose-function metrics (fV20, fV30, fV40, and functional mean-lung-dose (fMLD) generated by combining regional ventilation and dose), and (3) dose-subvolume metrics (sV20, sV30, sV40, and subvolume mean-lung-dose (sMLD) defined as the dose-volume metrics computed on the sub-volume of the lung with at least 60% of the quantified maximum ventilation status). Receiver operating characteristic (ROC) curve analysis and logistic regression analysis were used to evaluate the predictability of these metrics for RF. Results: In predicting airway dilation, the area under the ROC curve (AUC) values for (V20, MLD), (fV20, fMLD), and (sV20, and sMLD) were (0.76, 0.70), (0.80, 0.74) and (0.82, 0.80), respectively. The logistic regression p-values were (0.09, 0.18), (0.02, 0.05) and (0.004, 0.006), respectively. With regard to volume loss, the corresponding AUC values for these metrics were (0.66, 0.57), (0.67, 0.61) and (0.71, 0.69), and p-values were (0.95, 0.90), (0.43, 0.64) and (0.08, 0.12), respectively. Conclusion: The inclusion of regional ventilation function improved predictability of radiation fibrosis. Dose-subvolume metrics provided a promising method for incorporating functional information into the conventional dose-volume parameters for outcome assessment.

Objective: Positron emission tomography (PET)/CT scans can improve target definition in radiotherapy for non-small cell lung cancer (NSCLC). As staging PET/CT scans are increasingly available, we evaluated different methods for co-registration of staging PET/CT data to radiotherapy simulation (RTP) scans.Methods: 10 patients underwent staging PET/CT followed by RTP PET/CT. On both scans, gross tumour volumes (GTVs) were delineated using CT (GTVCT) and PET display settings. Four PET-based contours (manual delineation, two threshold methods and a source-to-background ratio method) were delineated. The CT component of the staging scan was co-registered using both rigid and deformable techniques to the CT component of RTP PET/CT. Subsequently rigid registration and deformation warps were used to transfer PET and CT contours from the staging scan to the RTP scan. Dice’s similarity coefficient (DSC) was used to assess the registration accuracy of staging-based GTVs following both registration methods with the GTVs delineated on the RTP PET/CT scan.Results: When the GTVCT delineated on the staging scan after both rigid registration and deformation was compared with the GTVCT on the RTP scan, a significant improvement in overlap (registration) using deformation was observed (mean DSC 0.66 for rigid registration and 0.82 for deformable registration, p50.008). A similar comparison for PET contours revealed no significant improvement in overlap with the use of deformable registration.Conclusions: No consistent improvements in similarity measures were observed when deformable registration was used for transferring PET-based contours from a staging PET/CT. This suggests that currently the use of rigid registration remains the most appropriate method for RTP in NSCLC.