John R. van Sörnsen de Koste

Evaluation of a target contouring protocol for 3D conformal radiotherapy in non-small cell lung cancer

BACKGROUND A protocol for the contouring of target volumes in lung cancer was implemented. Subsequently, a study was performed in order to determine the intra and inter-clinician variations in contoured volumes. MATERIALS AND METHODS Six radiation oncologists (RO) contoured the gross tumour volume (GTV) and/or clinical target volume (CTV), and planning target volume (PTV) for three patients with non-small cell lung cancer (NSCLC), on two separate occasions. These were, respectively, a well-circumscribed T1N0M0 lesion, an irregularly shaped T2N0M0 lesion, and a T2N2M0 tumour. Detailed diagnostic radiology reports were provided and contours were entered into a 3D planning system. The target volumes were calculated and beams-eye view (BEV) plots were generated to visualise differences in contouring. A software tool was used to expand the GTV and CTV in three dimensions for an automatically derived PTV. RESULTS Significant inter-RO variations in contoured target volumes were observed for all patients, and these were greater than intra-RO differences. The ratio of the largest to smallest contoured volume ranged from 1.6 for the GTV in the T1N0 lesion, to 2.0 for the PTV in the T2N2 lesion. The BEV plots revealed significant inter-RO variations in contouring the mediastinal CTV. The PTVs derived using a 3D margin programme were larger than manually contoured PTVs. These variations did not correlate with the experience of ROs. CONCLUSIONS Despite the use of an institutional contouring protocol, significant interclinician variations persist in contouring target volumes in NSCLC. Additional measures to decrease such variations should be incorporated into clinical trials.

Analysis and reduction of 3D systematic and random setup errors during the simulation and treatment of lung cancer patients with CT-based external beam radiotherapy dose planning

PURPOSE To determine the magnitude of the errors made in (a) the setup of patients with lung cancer on the simulator relative to their intended setup with respect to the planned treatment beams and (b) in the setup of these patients on the treatment unit. To investigate how the systematic component of the latter errors can be reduced with an off-line decision protocol for setup corrections. METHODS AND MATERIALS For 39 patients with CT planning, digitally-reconstructed radiographs (DRRs) were calculated for anterior-posterior and lateral beams. Retrospectively, the position of the visible anatomy relative to the planned isocenter was compared with the corresponding position on the digitized simulator radiographs using contour match software. The setup accuracy at the treatment unit relative to the simulator setup was measured for 40 patients for at least 5 fractions per patient in 2 orthogonal beams with the aid of an electronic portal imaging device (EPID). Setup corrections were applied, based on an off-line decision protocol, with parameters derived from knowledge of the random setup errors in the studied patient group. RESULTS The standard deviations (SD) of the simulator setup errors relative to the CT planning setup in the lateral, longitudinal, and anterior-posterior directions were 4.0, 2.8, and 2.5 mm, respectively. The SD of rotations around the anterior-posterior axis was 1.6 degrees and around the left-right axis 1.3 degrees. The setup error at the treatment unit had a small random component in all three directions (1 SD = 2 mm). The systematic components were larger, particularly in the longitudinal direction (1 SD = 3.6 mm), but were reduced with the decision protocol to 1 SD < 2 mm with, on average, 0.6 setup correction per patient. CONCLUSION Setup errors at the simulator, which become systematic errors if the simulation defines the reference setup, were comparable to the systematic setup errors at the treatment unit in case no off-line protocol would have been applied. Hence, the omission of a separate simulation step can reduce systematic errors as efficiently as the application of an off-line correction protocol during treatment. The random errors were sufficiently small to make an off-line protocol feasible.

CAN ELECTIVE NODAL IRRADIATION BE OMITTED IN STAGE III NON-SMALL-CELL LUNG CANCER? ANALYSIS OF RECURRENCES IN A PHASE II STUDY OF INDUCTION CHEMOTHERAPY AND INVOLVED-FIELD RADIOTHERAPY

PURPOSE To establish the recurrence patterns when elective mediastinal irradiation was omitted, patients with Stage III non-small-cell lung cancer were treated with sequential chemotherapy (CHT) and involved-field radiotherapy (RT). METHODS AND MATERIALS Fifty patients were treated with either two or four cycles of induction CHT, followed by once-daily involved-field RT to 70 Gy, delivered using three-dimensional treatment planning. The contoured gross tumor volume consisted of the pre-CHT tumor volume and nodes with a short-axis diameter of > or = 1 cm. Patients were reevaluated at 3 and 6 months after RT using bronchoscopy and chest CT. Elective nodal failure was defined as recurrence in the regional nodes outside the clinical target volume, in the absence of in-field failure. RESULTS Of 43 patients who received doses > or = 50 Gy, 35% were disease free at last follow-up; in-field recurrences developed in 27% (of whom 16% had exclusively in-field recurrences); 18% had distant metastases exclusively. No elective nodal failure was observed. The median actuarial overall survival was 18 months (95% confidence interval 14-22) and the median progression-free survival was 12 months (95% confidence interval 6-18). CONCLUSION Omitting elective mediastinal irradiation did not result in isolated nodal failure. Future studies of concurrent CHT and RT for Stage III non-small-cell lung cancer should use involved-field RT to limit toxicity.

Electronic portal image assisted reduction of systematic set-up errors in head and neck irradiation.

PURPOSE To quantify systematic and random patient set-up errors in head and neck irradiation and to investigate the impact of an off-line correction protocol on the systematic errors. MATERIAL AND METHODS Electronic portal images were obtained for 31 patients treated for primary supra-glottic larynx carcinoma who were immobilised using a polyvinyl chloride cast. The observed patient set-up errors were input to the shrinking action level (SAL) off-line decision protocol and appropriate set-up corrections were applied. To assess the impact of the protocol, the positioning accuracy without application of set-up corrections was reconstructed. RESULTS The set-up errors obtained without set-up corrections (1 standard deviation (SD)=1.5-2mm for random and systematic errors) were comparable to those reported in other studies on similar fixation devices. On an average, six fractions per patient were imaged and the set-up of half the patients was changed due to the decision protocol. Most changes were detected during weekly check measurements, not during the first days of treatment. The application of the SAL protocol reduced the width of the distribution of systematic errors to 1mm (1 SD), as expected from simulations. A retrospective analysis showed that this accuracy should be attainable with only two measurements per patient using a different off-line correction protocol, which does not apply action levels. CONCLUSIONS Off-line verification protocols can be particularly effective in head and neck patients due to the smallness of the random set-up errors. The excellent set-up reproducibility that can be achieved with such protocols enables accurate dose delivery in conformal treatments.

Lung Density Changes After Stereotactic Radiotherapy: A Quantitative Analysis in 50 Patients

PURPOSE Radiologic lung density changes are observed in more than 50% of patients after stereotactic body radiotherapy (SBRT) for lung cancer. We studied the relationship between SBRT dose and posttreatment computed tomography (CT) density changes, a surrogate for lung injury. METHODS AND MATERIALS The SBRT fractionation schemes used to treat Stage I lung cancer with RapidArc were three fractions of 18 Gy, five fractions of 11 Gy, or eight fractions of 7.5 Gy, prescribed at the 80% isodose. Follow-up CT scans performed at less than 6 months (n = 50) and between 6 and 9 months (n = 30) after SBRT were reviewed. Posttreatment scans were coregistered with baseline scans using a B-spline deformable registration algorithm. Voxel-Hounsfield unit histograms were created for doses between 0.5 and 50 Gy. Linear mixed effects models were used to assess the effects of SBRT dose on CT density, and the influence of possible confounders was tested. RESULTS Increased CT density was associated with higher dose, increasing planning target volume size, and increasing time after SBRT (all p < 0.0001). Density increases were apparent in areas receiving >6 Gy, were most prominent in areas receiving >20 Gy, and seemed to plateau above 40 Gy. In regions receiving >36 Gy, the reduction in air-filled fraction of lung after treatment was up to 18%. No increase in CT density was observed in the contralateral lung receiving ≥3 Gy. CONCLUSIONS A dose-response relationship exists for quantitative CT density changes after SBRT. A threshold of effect is seen at low doses, and a plateau at highest doses.

Beam intensity modulation using tissue compensators or dynamic multileaf collimation in three-dimensional conformal radiotherapy of primary cancers of the oropharynx and larynx, including the elective neck

INTRODUCTION The treatment of midline tumors in the head and neck by conventional radiotherapy almost invariably results in xerostomia. This study analyzes whether a simple three-dimensional conformal radiotherapy (3D-CRT) technique with beam intensity modulation (BIM) (using a 10-MV beam of the MM50 Racetrack Microtron) can spare parotid and submandibular glands without compromising the dose distribution in the planning target volume (PTV). METHODS For 15 T2 tumors of the tonsillar fossa with extension into the soft palate (To) and 15 T3 tumors of the supraglottic larynx (SgL), conventional treatment plans, consisting of lateral parallel opposed beams, were used for irradiation of both the primary tumor (70 Gy) and the elective neck regions (46 Gy). Separately, for each tumor a 3-D conformal treatment plan was developed using the 3-D computer planning system, CadPlan, and Optimize, a noncommercial program to compute optimal beam profiles. Beam angles were selected with the intention of optimal sparing of the salivary glands. The intensity of the beams was then modulated to achieve a homogeneous dose distribution in the target for the given 3D-CRT techniques. The dose distributions, dose-volume histograms (DVHs) of target and salivary glands, tumor control probabilities (TCPs), salivary gland volumes absorbing a biologically equivalent dose of greater than 40 or 50 Gy, and normal tissue complication probabilities (NTCPs) of each treatment plan were computed. The parameters of the 3D-CRT plans were compared with those of the conventional plans. RESULTS In comparison with the conventional technique, the dose homogeneity in the target volume was improved by the conformal technique for both tumor sites. In addition, for the SgL conformal technique, the average volumes of the parotid glands absorbing a BED of greater than 40 Gy (V40) decreased by 23%, and of the submandibular glands by 7% (V40) and 6% (V50). Consequently, the average NTCPs for the parotid and submandibular glands were reduced by 7% and 6%, respectively. For the To conformal techniques, the V40 of the parotid glands was decreased on average by 31%, resulting in an average reduction of the NTCP by 49%. Both the average V50 and the NTCP of the submandibular glands were decreased by 7%. CONCLUSION For primary tumors of the oropharynx, the parotid glands could be spared to a considerable degree with the 3D-CRT technique. However, particularly the ipsilateral submandibular gland could not be spared. For primary tumors of the larynx, the 3D-CRT technique allows sparing of all salivary glands to a considerable and probably clinically relevant degree. Moreover, the conformal techniques resulted in an increased dose homogeneity in the PTV of both tumor sites.

Variations in Target Volume Definition for Postoperative Radiotherapy in Stage III Non–Small-Cell Lung Cancer: Analysis of an International Contouring Study

PURPOSE Postoperative radiotherapy (PORT) in patients with completely resected non-small-cell lung cancer with mediastinal involvement is controversial because of the failure of earlier trials to demonstrate a survival benefit. Improved techniques may reduce toxicity, but the treatment fields used in routine practice have not been well studied. We studied routine target volumes used by international experts and evaluated the impact of a contouring protocol developed for a new prospective study, the Lung Adjuvant Radiotherapy Trial (Lung ART). METHODS AND MATERIALS Seventeen thoracic radiation oncologists were invited to contour their routine clinical target volumes (CTV) for 2 representative patients using a validated CD-ROM-based contouring program. Subsequently, the Lung ART study protocol was provided, and both cases were contoured again. Variations in target volumes and their dosimetric impact were analyzed. RESULTS Routine CTVs were received for each case from 10 clinicians, whereas six provided both routine and protocol CTVs for each case. Routine CTVs varied up to threefold between clinicians, but use of the Lung ART protocol significantly decreased variations. Routine CTVs in a postlobectomy patient resulted in V(20) values ranging from 12.7% to 54.0%, and Lung ART protocol CTVs resulted in values of 20.6% to 29.2%. Similar results were seen for other toxicity parameters and in the postpneumectomy patient. With the exception of upper paratracheal nodes, protocol contouring improved coverage of the required nodal stations. CONCLUSION Even among experts, significant interclinician variations are observed in PORT fields. Inasmuch as contouring variations can confound the interpretation of PORT results, mandatory quality assurance procedures have been incorporated into the current Lung ART study.

Motion Analysis of 100 Mediastinal Lymph Nodes: Potential Pitfalls in Treatment Planning and Adaptive Strategies

PURPOSE The motion of mediastinal lymph nodes may undermine local control with involved-field radiotherapy. We studied patterns of nodal and tumor motion in 41 patients with lung cancer. METHODS AND MATERIALS Four-dimensional (4D) computed tomography planning scans were retrospectively evaluated to identify patients with clearly visible mediastinal lymph nodes. One hundred nodes from 14 patients with Stage I and 27 patients with Stage III were manually contoured in all 4D computed tomography respiratory phases. Motion was derived from changes in the nodal center-of-mass position. Primary tumors were also delineated in all phases for 16 patients with Stage III disease. Statistical analysis included a multivariate mixed-effects model of grouped data. RESULTS Average 3D nodal motion during quiet breathing was 0.68 cm (range, 0.17-1.64 cm); 77% moved greater than 0.5 cm, and 10% moved greater than 1.0 cm. Motion was greatest in the lower mediastinum (p = 0.002), and nodes measuring 2 cm or greater in diameter showed motion similar to that in smaller nodes. In 11 of 16 patients studied, at least one node moved more than the corresponding primary tumor. No association between 3D primary tumor motion and nodal motion was observed. For mobile primary tumors, phase offsets between the primary tumor and nodes of two or more and three or more phases were observed for 33% and 12% of nodes, respectively. CONCLUSIONS Mediastinal nodal motion is common, with phase offsets seen between the primary tumor and different nodes in the same patient. Patient-specific information is needed to ensure geometric coverage, and adaptive strategies based solely on the primary tumor may be misleading.

EVALUATION OF FOUR-DIMENSIONAL COMPUTED TOMOGRAPHY-BASED INTENSITY-MODULATED AND RESPIRATORY-GATED RADIOTHERAPY TECHNIQUES FOR PANCREATIC CARCINOMA

PURPOSE To compare conformal radiotherapy (CRT), intensity-modulated radiotherapy (IMRT), and respiration-gated radiotherapy (RGRT) planning techniques for pancreatic cancer. All target volumes were determined using four-dimensional computed tomography scans (4D CT). METHODS AND MATERIALS The pancreatic tumor and enlarged regional lymph nodes were contoured on all 10 phases of a planning 4D CT scan for 10 patients, and the planning target volumes (PTV(all phases)) were generated. Three consecutive respiratory phases for RGRT delivery in both inspiration and expiration were identified, and the corresponding PTVs (PTV(inspiration) and PTV(expiration)) and organ at risk volumes created. Treatment plans using CRT and IMRT, with and without RGRT, were created for each PTV. RESULTS Compared with the CRT plans, IMRT significantly reduced the mean volume of right kidney exposed to 20 Gy from 27.7% +/- 17.7% to 16.0% +/- 18.2% (standard deviation) (p < 0.01), but this was not achieved for the left kidney (11.1% +/- 14.2% to 5.7% +/- 6.5%; p = 0.1). The IMRT plans also reduced the mean gastric, hepatic, and small bowel doses (p < 0.01). No additional reductions in the dose to the kidneys or other organs at risk were seen when RGRT plans were combined with either CRT or IMRT, and the findings for RGRT in end-expiration and end-inspiration were similar. CONCLUSION 4D CT-based IMRT plans for pancreatic tumors significantly reduced the radiation doses to the right kidney, liver, stomach, and small bowel compared with CRT plans. The additional dosimetric benefits from RGRT appear limited in this setting.

Impact of Audio-Coaching on the Position of Lung Tumors

PURPOSE Respiration-induced organ motion is a major source of positional, or geometric, uncertainty in thoracic radiotherapy. Interventions to mitigate the impact of motion include audio-coached respiration-gated radiotherapy (RGRT). To assess the impact of coaching on average tumor position during gating, we analyzed four-dimensional computed tomography (4DCT) scans performed both with and without audio-coaching. METHODS AND MATERIALS Our RGRT protocol requires that an audio-coached 4DCT scan is performed when the initial free-breathing 4DCT indicates a potential benefit with gating. We retrospectively analyzed 22 such paired scans in patients with well-circumscribed tumors. Changes in lung volume and position of internal target volumes (ITV) generated in three consecutive respiratory phases at both end-inspiration and end-expiration were analyzed. RESULTS Audio-coaching increased end-inspiration lung volumes by a mean of 10.2% (range, -13% to +43%) when compared with free breathing (p = 0.001). The mean three-dimensional displacement of the center of ITV was 3.6 mm (SD, 2.5; range, 0.3-9.6mm), mainly caused by displacement in the craniocaudal direction. Displacement of ITV caused by coaching was more than 5 mm in 5 patients, all of whom were in the subgroup of 9 patients showing total tumor motion of 10 mm or more during both coached and uncoached breathing. Comparable ITV displacements were observed at end-expiration phases of the 4DCT. CONCLUSIONS Differences in ITV position exceeding 5 mm between coached and uncoached 4DCT scans were detected in up to 56% of mobile tumors. Both end-inspiration and end-expiration RGRT were susceptible to displacements. This indicates that the method of audio-coaching should remain unchanged throughout the course of treatment.