[en] In early stage non-small cell lung cancer (N.S.C.L.C.), recent data from both prospective clinical trials and single institutions indicate that local control rates in excess of 88% can be achieved using stereotactic radiotherapy (S.R.T.). Treatment-related toxicity is uncommon when 'risk-adapted' fractionation schemes are applied, with lower dose per fraction used for larger tumors and when the planning target volume is in the proximity of critical structures. Both the superior outcome and convenience of fewer visits have led to a preference for S.R.T. over conventional radiotherapy in countries such as Japan and the Netherlands. Reports on outcomes of S.R.T. in patients unfit to undergo surgery may underestimate late toxicity as such patients have significant non-cancer related mortality. The evolution of technology has allowed for further improvements in the accuracy and speed of S.R.T. delivery. Recent advances such as on-board imaging and intensity-modulated arc delivery techniques have improved treatment accuracy and tolerability, as well as the confidence of clinicians in applying S.R.T. outside the setting of specialized tertiary institutions. Studies comparing primary surgery with S.R.T. are underway, but the available data are compelling enough to allow S.R.T. to be considered an established treatment option in patients who are aged 75 years and older, and in whom the estimated risks of postoperative mortality rates are high. The clinical development of S.R.T. will be greatly facilitated by improvements in diagnostic procedures for peripheral pulmonary nodules. However, treatment without pathological confirmation may be justified in medically inoperable patients if the risk of malignancy is sufficiently high as to warrant an invasive diagnostic procedure. (authors)

[en] Purpose: To identify visible structures in the thorax which exhibit little internal motion during irradiation and, to determine random and systematic setup deviations in lung cancer patients with the use of these structures. Methods: Ten patients with lung cancer were set up in the supine position, and aligned using lasers. No immobilization devices were used. With an electronic portal imaging device (Siemens Beam View^PLUS), 12 sequential images (exposure 0.54 sec.; processing time 1.5 sec.) were obtained during a single fraction of radiotherapy. These 'movie loops' were generated for the A-P fields during each of 3-5 fractions. In order to determine the mobility of internal structures during each fraction, visible structures such as the trachea, carina, the upper chest wall, aortic arch, clavicle and paraspinal line were contoured manually in each image and matched with the first image of the corresponding movie loop by means of a cross-correlation algorithm. Translations in the cranial and lateral directions and in-plane rotations were determined for each structure separately. As the reference image represents a random position, relative movements were determined by comparing the translations and rotation for every image to the calculated means per movie-loop. Standard deviations of the relative movements were determined for each structure and each patient. Patient setup was evaluated for 15 patients with lung cancer. Setup was not corrected at any time during the treatment. The electronic portal images of each fraction were matched with the digitized simulator films by using a combination of the structures which had been determined to be relatively stable in the infra-fractional analysis. Results: In the infra-fractional analysis 120 to 380 matches were made per structure (a total of 1400). The standard deviation (SD) of translations in the lateral direction was small (≤1 mm) for the trachea, thoracic wall, paraspinal line and aortic arch. This was also the case for the SD of the translations in the cranial direction of the clavicle, aortic arch and upper thoracic wall. The carina was found to be relatively mobile (up to 6 mm) in both directions. The SD for in-plane rotations was negligible (<0.5 deg.) for all structures. The interpatient variation was very small (SD < 0.5 mm). In a preliminary analysis of patient setup, the random errors for translations are 2.0 mm in the lateral direction and 2.4 mm in the cranial direction (1 SD). The standard deviations of systematic errors are about 3 mm in both directions. In plane rotations were found to be negligible. Conclusions: We have identified a number of structures which exhibit little internal motion in the frontal plane, and recommend that a combination of these structures be used as anatomic landmarks for setup verification during radiotherapy of thoracic tumors. Preliminary results indicate that setup errors of patients with lung cancer in our center appear to be acceptable, even though no specific immobilization devices were used

[en] Purpose: Recently, there has been an interest in incorporating functional information in treatment planning especially in thoracic tumors. The rationale is that healthy lung regions need to be spared from radiation if possible to help achieve better control on toxicity. However, it is still unclear whether high functioning regions need to be spared or have more capacity to deal with the excessive radiation as compared to the compromised regions of the lung. Our goal with this work is to establish the tools by which we can establish a relationship between pre-treatment lung function, dose, and radiographic outcomes of lung toxicity. Methods: Treatment planning was performed using a single phase of a 4DCT scan, and follow-up anatomical CT scans were performed every 3 months for most patients. In this study, we developed the pipeline of tools needed to analyze such a large dataset, while trying to establish a relationship between function, dose, and outcome. Pre-treatment lung function was evaluated using a recently published technique that evaluates Fractional Regional Ventilation (FRV). All images including the FRV map and the individual follow-up anatomical CT images were all spatially matched to the planning CT using a diffusion based Demons image registration algorithm. Change in HU value was used as a metric to capture the effects of lung toxicity. To validate the findings, a radiologist evaluated the follow-up anatomical CT images and scored lung toxicity. Results: Initial experience in 1 patient shows a relationship between the pre-treatment lung function, dose and toxicity outcome. The results are also correlated to the findings by the radiologist who was blinded to the analysis or dose. Conclusion: The pipeline we have established to study this enables future studies in large retrospective studies. However, the tools are dependent on the fidelity of 4DCT reconstruction for accurate evaluation of regional ventilation. Patent Pending for the technique presented in this work to evaluate FRV incorporating mass correction

[en] 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.

[en] Background and purposeTo implement a robust and fast stereotactic MR-guided adaptive radiation therapy (SMART) online strategy in locally advanced pancreatic cancer (LAPC).

[en] Using three dimensional (3D) conformal radiotherapy (CRT) techniques for elective neck irradiation (ENI) may allow for local disease control to be maintained while diminishing xerostomia by eliminating major salivary glands (or parts thereof) from the treatment portals. The standardization of CT based target volumes for the clinically negative (elective) neck is a prerequisite for 3DCRT. The aim of the present study was to substantially modify an existing ('original') CT-based protocol for the delineation of the neck tar-et volume, into a more practical ('simplified') protocol. This will allow for rapid contouring and the implementation of conformal ENI in routine clinical procedures. An earlier ('original') version of the CT-based definition for elective neck node re-ions 2-5 was re-evaluated, using 15 planning CT scans of previously treated patients. The contouring guidelines were simplified by (1) using a smaller number of easily identifiable soft tissue- and bony anatomical landmarks, which in turn had to be identified in only a limited number of CT slices, and (2) by subsequently interpolating the contoured lymph node regions. The adequacy of target coverage and the sparing using both 'original' and 'simplified' delineation protocols was evaluated by DVH analysis after contouring the primary tumor, the neck and the major salivary glands in a patient with supraglottic laryngeal (SGL) carcinoma who was treated using a 3DCRT technique. The BEV projections of the 'original' and the 'simplified' versions of the 3D elective neck target showed good agreement and were found to be reproducible. The DVH's of the target and parotid glands were not significantly different using both contouring protocols. The 'simplified' protocol for the delineation of the 3D elective neck target produced both comparable target coverage and sparing of the major salivary glands. When used together with an interpolation program, this 'simplified' protocol substantial reduced the contouring time and makes ENI with sparing of the major salivary glands a practical and achievable goal. (author)

[en] The toxicity of endobronchial brachytherapy (EB), in particular fatal haemoptysis and bronchial wall necrosis, has been correlated with the total dose, fraction size, volume encompassed by the 100% isodose, and a proximal tumor location. We describe a CT-based planning method which, by improving target volume definition and volumeric dose information, can improve the therapeutic ratio of EB. Sixteen CT-assisted EB procedures were performed in patients who were treated with palliative high-dose rate EB. The CT data were used to analyze applicator position in relation to anatomy. An example of a three-dimensional optimized treatment plan was generated and analyzed using different types of dose-volume histograms. The procedure was well tolerated by patients and no post-procedure complications were observed. The bronchial applicator was eccentrically positioned at the level of the carina/mainstem bronchus in 12 (of 14) CT scans. A planning CT prior to EB was not found to be useful as the final target volume and/or the final applicator position were not reliably predicted before the therapeutic bronchoscopy. CT-scans performed with the applicator in situ allowed the bronchial segments in the target volume to be identified and enabled dose prescription to the bronchial mucosa. CT-assisted EB is feasible and underlines the need for using centered applicators for proximally located tumors. By enabling accurate mucosal dose prescription, CT-assisted EB may reduce the toxicity of fractionated EB in the curative setting. However, faster on-line EB treatment planning is needed for the routine clinical application of this technique. (author)

[en] We read with interest the article titled 'Single-Arc IMRT?' (Bortfeld and Webb 2009 Phys. Med. Biol. 54 N9-20) and feel it imperative to draw the attention of your readers to comments suggesting that the authors may not be fully aware of current developments in this field. As their paper was first submitted on 19th of August 2008, it could not have taken into account data presented at the AAPM, ESTRO and ASTRO meetings in 2008. In this letter, we would like to clarify some relevant aspects of RapidArc (Varian Medical Systems) as a modality for delivering single-arc treatment. (letter to the editor)

[en] Purpose: High local control rates can be achieved using stereotactic radiotherapy in Stage I non-small-cell lung cancer (NSCLC), but reports have suggested that toxicity may be of concern. We evaluated early clinical outcomes of 'risk-adapted' fractionation schemes in patients treated in a single institution. Methods and Materials: Of 206 patients with Stage I NSCLC, 81% were unfit to undergo surgery and the rest refused surgery. Pathologic confirmation of malignancy was obtained in 31% of patients. All other patients had new or growing 18F-fluorodeoxyglucose positron emission tomography positive lesions with radiologic characteristics of malignancy. Planning four-dimensional computed tomography scans were performed and fractionation schemes used (3 x 20 Gy, 5 x 12 Gy, and 8 x 7.5 Gy) were determined by T stage and risk of normal tissue toxicity. Results: Median overall survival was 34 months, with 1- and 2-year survivals of 81% and 64%, respectively. Disease-free survival (DFS) at 1 and 2 years was 83% and 68%, respectively, and DFS correlated with T stage (p = 0.002). Local failure was observed in 7 patients (3%). The crude regional failure rate was 9%; isolated regional recurrence was observed in 4%. The distant progression-free survival at 1 and 2 years was 85% and 77%, respectively. SRT was well tolerated and severe late toxicity was observed in less than 3% of patients. Conclusions: SRT is well tolerated in patients with extensive comorbidity with high local control rates and minimal toxicity. Early outcomes are not inferior to those reported for conventional radiotherapy. In view of patient convenience, such risk-adapted SRT schedules should be considered treatment of choice in patients presenting with medically inoperable Stage I NSCLC

[en] 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 (R² = 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. (orig.)