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M. Zwitter

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    MO17 - Radiotherapy I: Stereotactic Ablative Body Radiotherapy (ID 106)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 12
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      MO17.01 - Response assessment of Stereotactic Ablative Body Radiotherapy (SABR) for pulmonary metastases: utility of 4D-FDG-PET and CT perfusion (ID 2225)

      16:15 - 17:45  |  Author(s): S. Siva, R. Hicks, B. Sawyer, E. Pun, B. Chesson, M. Samuel, G. Wright, P. Antippa, J. Callahan, T. Kron, M. Macmanus, D. Ball

      • Abstract
      • Presentation
      • Slides

      Background
      Response assessment using conventional RECIST criteria after SABR of lung targets can be confounded by fibrotic response. The purpose of this study was to evaluate the utility of 4D-FDG-PET/CT and CT perfusion scans in the response assessment of single fraction SABR for inoperable pulmonary oligometastases.

      Methods
      This is a prospective ethics approved clinical study of patients undergoing single fraction SABR with 26Gy for pulmonary metastases. Eligible patients had 1-2 metastases with no extrathoracic disease on staging FDG-PET. Serial 3D / 4D-FDG-PET and CT perfusion studies were performed at baseline, 14 days and 70 days after therapy. Two radiologists independently reported CT perfusion scans.

      Results
      At a median follow-up of 16 months (range 3-27), 10 patients with 13 metastases received SABR. A further 7 patients (41%) were screened from the study due to interval progression of disease between the time of the original FDG-PET and trial 4D-FDG-PET / perfusion CT. The mean time between the original FDG-PET and trial scans was 62 days. No patient progressed locally, 7/10 patients progressed distantly of which 2/7 received subsequent SABR. At the end of study period, 5/10 patients are alive without disease. The median progression free survival was 14 months. The change in SUVmax from baseline was higher on 3D than 4D-PET by a mean of 20.6% (range 0.2%-47.2%) at 14 days and 14.8% (range 0-37.8%) at 70 days. Overall, the SUVmax increased at 14 days (mean 104.9%, p<0.01) and decreased at 70 days (mean=55.5%, p<0.01), despite persistent morphological lesions on the concurrent late timepoint CT. There was strong level of inter-observer agreement of CT perfusion interpretation with a median intraclass correlation coefficient of 89% (range 57%-98%). Perfusion parameters of Time to Peak Blood Flow and Blood Volume showed a median increase of 18.8% and 23.0% at 2 weeks post-therapy and decreased below baseline by a median 7.0% and 14.0% at 70 days (non-significant).

      Conclusion
      High rates of interval progression between staging scans indicates a need to expedite management of oligometastases in a timely fashion. Increased tumour perfusion and FDG-PET intensity at 2 weeks post-RT is likely due to an inflammatory response to large single dose SABR. Late PET response was associated with tumour control despite CT apparent morphological lesions. Conventional 3D PET may overestimate change in PET intensity post SABR as compared to 4D PET. These findings, in particular CT perfusion findings, require a larger patient cohort for validation.

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      MO17.02 - Radical Radiotherapy for Non-small Cell Lung Cancer - is it the end for 2 Gray per fraction? (ID 2247)

      16:15 - 17:45  |  Author(s): N. O'Rourke

      • Abstract
      • Presentation
      • Slides

      Background
      The standard of care worldwide for radiation dose scheduling in NSCLC has historically been 2Gy per fraction treating once daily over six weeks. The CHART regimen of accelerated hyperfractionated treatment first demonstrated significant survival benefit from a two week radical course, attributed to reduced repopulation and improved local control. A recent individual patient data meta-analysis confirms significant survival benefit from accelerated radiotherapy[1]. Meantime the evolving data on stereotactic radiotherapy treating early stage lung cancer over two weeks or less suggests marked improvement in local control rates compared with historical populations treated with conventional fractionation[2]. The latest challenge to 2Gy per fraction comes from the early stop to the dose escalation arm of RTOG 0617 with 74Gy actually appearing inferior to the 60Gy arm. We postulate that overall treatment time is a key factor in lung cancer radiotherapy outcomes and that standards of care need to be reviewed. This paper examines the current international guidelines on radical radiotherapy schedules, evaluates the supporting evidence and proposes new priorities for research.

      Methods
      Five international guidelines on the management of lung cancer were reviewed. All were published 2010-2013: ESMO Clinical Practice Guideline on early stage and locally advanced lung cancer 2010, NICE guideline (England and Wales) 2011, Australian Government Clinical Practice Guideline for treatment of lung cancer 2012, Cancer Care Ontario evidence based series lung cancer guideline 2013, National Comprehensive Cancer Network (NCCN) Lung Cancer guideline v2.2013. Recommendations on radical radiotherapy dose and fractionation for NSCLC were collated from each guideline together with the references cited in support of these recommendations to assess levels of evidence.

      Results
      Two guidelines specifically recommended hypofractionated SBRT for early stage inoperable disease -NICE and NCCN. The Australian guideline stated uncertainty over relative benefit SBRT versus conventional fractionation in stage I disease. England, Ontario and Australia all included CHART regimen as treatment of choice for stage II/III radical patients not receiving chemotherapy. Cancer Care Ontario undertook specific review of altered fractionation schedules identifying lack of evidence for hyperfractionation but suggesting possible benefit for hypofractionation. All five guidelines specified standard care, if given with chemotherapy, of conventional fraction size 2Gy: Ontario, ESMO and Australian guidance was a minimum of 60Gy in 30 fractions. NCCN offered a range of 60-74Gy at 2Gy/fraction. NICE alone proposed alternative standard of 55Gy in 20 fractions, a common UK schedule, or the option of 64-66Gy at 2Gy/fraction

      Conclusion
      International guidelines lag behind the emerging evidence for lack of benefit from dose escalation at 2Gy/fraction and apparent benefit from shorter treatment courses . We propose that accelerating treatment with hypofractionation and shorter overall treatment times should be the priority for radiotherapy development. We discuss current and pending trials examining this approach. 1. Mauguen A, Le Pechoux C, Saunders M et al: Hyperfractionated or accelerated radiotherapy in lung cancer: an individual patient data meta-analysis. J Clin Oncol 30:2788-2797, 2012 2. Timmerman R, Paulus R, Gavin J et al: Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA 303:1070-1076, 2010

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      MO17.03 - Incidental Prophylactic Nodal Irradiation and Patterns of Nodal Relapse in Inoperable Early Stage NSCLC Patients Treated with SBRT: A Case-Matched Analysis (ID 2024)

      16:15 - 17:45  |  Author(s): L. Lao, A. Hope, A. Brade, A. Bezjak, E.P. Saibishkumar, M. Giuliani, A. Sun, B.C.J. Cho

      • Abstract
      • Presentation
      • Slides

      Background
      Reported non-small cell lung cancer (NSCLC) nodal failure rates following stereotactic body radiotherapy (SBRT) are lower than those reported in the surgical series when matched for stage. We hypothesize that this effect is due to incidental prophylactic nodal irradiation.

      Methods
      A prospectively collected group of medically inoperable early stage NSCLC patients (n=179) from 2004 to 2010 was used to identify a patient cohort with nodal relapses (n=19). These cases were matched, 1:2, to controls, controlling for tumour volume (i.e. same or greater) and tumour location (i.e. same lobe). Reference (normalized total) point doses at the ipsilateral hilum and carina, demographic data, and clinical outcomes were extracted from the medical record. Multivariate logistical regression analyses determined variables of interest.

      Results
      The case and control cohorts were well matched with respect to age, sex, method of nodal staging, SUVmax, histology subtype, dose and length of follow up.. The controls, as expected, had larger gross tumour volumes (p=0.02). The mean hilar doses were 9.6 and 22.4 Gy for cases and controls, respectively (p=0.014). Similarly, the mean carinal doses were 7.0 and 9.2 Gy, respectively (p=0.13). The mean ipsilateral hilar doses were 19.8 and 3.6 Gy for ipsilateral non-hilar and hilar nodal relapses, respectively (p=0.01). The conditional density plot appears to demonstrate an inverse dose-effect relationship between ipsilateral hilar normalized total dose and risk of ipsilateral hilar relapse (Figure 1).Figure 1

      Conclusion
      Incidental hilar dose greater than 20 Gy (normalized to 2Gy/fraction) appears to be correlated with lack of hilar relapses in inoperable early stage NSCLC patients treated with SBRT.

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      MO17.04 - Endobronchial Fiducial Marker Safety and Stability (ID 696)

      16:15 - 17:45  |  Author(s): D.A. Nader

      • Abstract
      • Presentation
      • Slides

      Background
      Fiducial markers enable lesion tracking and localization with radiosurgery. Complications with percutaneous insertion are very common with pneumothorax rate reported as high as 67%, chest tube insertion 22% and migration of marker 19%. The purpose of this study was to assess complications associated with the bronchoscopic placement of a new commercial fiducial marker, designed for bronchoscopic insertion and to reduce migration. Twenty-one consecutive patients are reviewed in which 60 Cobra® (SuperDimension) fiducial markers were placed using electromagnetic navigational bronchoscopy. Accuracy of placement, utility of each marker, complications and migration are reported.

      Methods
      The use of these markers was approved by a advisory committee at our institution. Records of 21 consecutive patients (12 men, 9 women; mean age 61) referred to the Interventional Pulmonary Division for fiducial marker placement before initiation of cyber knife radiosurgery (Accuray, Sunnyvale CA) between December 15, 2012 and June 15, 2013. Indications for radiosurgery included non-surgical patients with nonsmall cell lung cancer and metatatic disease to the lungs from colorectal carcinoma and renal cell carcinoma. Our institution's radiation oncologist requested between one and three fiducials placed within or adjacent to each lesion. A total of 60 Cobra® fiducial markers were placed. In each insertion procedure, a computerized tomogram of the chest was used to preplan ideal insertion site and fiducial location in relation to tumor mass. Bronchoscopy was performed, using the SuperDimension planning and navigation, 1 to 3 Cobra® fiducial markers were placed in proximity to 22 different tumors.

      Results
      There were no instances of pneumothorax, with patient followup to one week. There no instances of fiducial migration greater than 3 mm from insertion site. There were 7 episodes of post procedure events, which included cough, dyspnea and hypoxemia. All events resolved prior to patient discharge from the outpatient treatment area. Imaging included chest radiograph, post procedure, on same day and CT chest within 1 week of procedure.

      Conclusion
      In this limited series, the Cobra® fiducial marker, using bronchoscopy and SuperDimension planning and navigation resulted in no instances of pneumothorax and no significant fiducial migration. This contrasts many reports of percutaneous fiducial placements regarding complications and migration.

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      MO17.05 - Recurrence, Survival, and Toxicity after Stereotactic Lung Radiotherapy (SBRT) for Central versus Peripheral Stage I Non-Small Cell Lung Cancer (NSCLC): Results from an International Collaborative Research Group (ID 3436)

      16:15 - 17:45  |  Author(s): I.S. Grills, V.S. Mangona, A. Hope, J. Belderbos, M. Werner-Wasik, J.J. Sonke, J. Bissonette, D. Ionascu, Y. Xiao, A. Toussaint, M. Guckenberger

      • Abstract
      • Presentation
      • Slides

      Background
      SBRT is an accepted safe and effective treatment modality for peripheral (P) stage I NSCLC tumors. Concern of excessive toxicity, however, limits its use for central (C) tumors. This study evaluates outcomes and toxicities after cone-beam CT (CBCT) image-guided SBRT for central vs. peripheral NSCLC.

      Methods
      959 lung tumors were treated with lung SBRT from 1998-2012 at five international centers participating in the Elekta Collaborative Lung Research Group; 98% underwent online CBCT IGRT. 100 cases were classified as Central (C) and 869 Peripheral (P), defined as ≤2cm vs. >2cm from the proximal bronchial tree, respectively. Staging included chest CT and routine chemistry for all; 93% had PET staging (mean time PET to SBRT 6.4 weeks); 6% had mediastinal sampling (mediastinoscopy or endobronchial ultrasound). 61% had tumor biopsy (84% C vs. 59% P, p<0.001). 89% were medically inoperable with mean baseline FEV1 of 1.6L (63% of predicted) and mean baseline DLCO of 12.1 ml/min/mmHg (56% of predicted). Mean age was 74y (42-93) with a large range in ECOG performance status (27%; 47%; 23%; 26% for 0-3, respectively). Clinical stage was T1aN0 44%, T1bN0 30%, T2aN0 23%, T2bN0 32%. Mean tumor maximum dimension was 2.5cm (range 0.5-8.5cm); C tumors were larger (mean 3.lcm vs. 2.4 cm, p<0.001). Mean SBRT prescription dose was 51.5±6.4 Gy, with mean dose per fraction of 14.5±4.0 Gy in 3.9±1.5 fractions. Mean biological equivalent dose (BED) was 126.6±26.6 Gy, higher for P vs. C tumors (129.2 vs. 104.0 Gy, p<0.001. Chemotherapy was administered more for C (9%) than P tumors (2%), p<0.001. Groups were compared with t-test & chi-square. Competing risks analyses were used, accounting for the competing risk of death.

      Results
      Mean follow-up for all cases was 1.8y (0.1-7.7y; mean potential follow-up 3.4y), similar for C&P. C tumors had higher Local Failure (LF) (3y-LF 16.2%C vs. 5.9%P; 5y-LF 20.4%C vs. 8.3%P, p<0.001), similar regional nodal recurrences (RR) (3y-RR 12%C vs.12%P, p=0.69) and distant metastases (DM) (3y-DM 19%C vs 20%P, p=0.75), lower cause-specific survival (CSS) (3yr-CSS 75%C vs. 88%P, p<0.001), but similar overall survival (OS) (3y-OS 50%C vs. 51%P, p=0.70). Grade > 2 pneumonitis was higher for C tumors (8%C vs. 1%P, p<0.001). Incidence of grade 3 pneumonitis, chest wall pain/myositis, rib fracture, and skin dermatitis were rare (0.8%, 0.5%, 0.4%, 0.6% respectively for all) with no differences between C&P. No grade 4 toxicities were noted, though 2 cases (1C & 1P) of fatal pneumonitis were potentially attributable to SBRT. On multivariate analysis, BED (HR:0.975, p<0.001) predicted CSS, and both BED (HR:0.978, p=0.002) and baseline SUVmax (HR:1.04, p=0.001) predicted LF. Weeks from PET-staging until SBRT (HR:1.25, p=0.004) and the percent of lungs receiving >20 Gy (HR:1.063, p=0.001) were the strongest independent predictors of OS.

      Conclusion
      In this large data set, pneumonitis was higher for central tumors, but both central & peripheral SBRT were safe with similar overall and cause-specific survival. LF was higher for central tumors, which were larger, had higher baseline SUVmax, and received lower dose. Results of the ongoing RTOG 0813 dose-finding study for central tumors are awaited.

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      MO17.06 - DISCUSSANT (ID 3933)

      16:15 - 17:45  |  Author(s): M. Hatton

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MO17.07 - The cost of stereotactic body radiotherapy in early-stage lung cancer: a multicenter cost-calculation. (ID 1772)

      16:15 - 17:45  |  Author(s): Y. Lievens, C. Obyn, A. Mertens, D. Van Halewyck, H. Engels, F. Hulstaert

      • Abstract
      • Presentation
      • Slides

      Background
      In the framework of a coverage with evidence development program on innovative radiotherapy techniques in Belgium, the cost of stereotactic body radiotherapy (SBRT) was calculated and compared to the cost of more standardized 3D-conformal (3D-CRT) and intensity-modulated (IMRT) radiotherapy treatments.

      Methods
      Activity-Based Costing methodology was used to calculate resource costs of radiotherapy treatments delivered in ten operational Belgian departments. Cost inputs were defined as personnel costs (number of full-time equivalents (FTE) devoted to the actual radiotherapy process times reference wages according to the guidelines of the Belgian Health Care Knowledge Centre (KCE)), equipment costs (including maintenance and upgrade) and specific material costs. Following KCE guidelines, overhead was accounted at 56% of global costs excluding physician wages. The activities in scope comprised all activities performed during the radiotherapy process from the first consultation, over treatment preparation, delivery and quality assurance until completion of the treatment. Products included all radiotherapy treatments delivered in each specific department and combined indication with treatment site and technical complexity. In view of the comparative analysis, products were aggregated into larger categories.

      Results
      The average cost of all SBRT treatments was calculated at 6,221€ (range 3,104€ - 12,649€) and compared favorably to the average cost of standard fractionated 3D-CRT (5,919€, range 4,557€ - 6,564€) and IMRT (7,379€, range 5,054€ - 8,733€). The average cost of hypofractionated 3D-CRT and IMRT was lower (3,993€ res. 4,730€). Apart from differences in investment costs, the relatively larger variability in fraction number and in time requirements for individual personnel types performing the radiotherapy activities explain the larger spread in treatment cost of SBRT compared to more standardized radiotherapy treatments. The figure demonstrates these differences for various technical SBRT solutions and for different 3D-CRT and IMRT fractionation schedules. The overall averages are shown by the bars, minimum and maximum center averages by the error bars. The number of centers is mentioned between brackets. Activity times shown combine time per personnel with number of FTE. Figure 1

      Conclusion
      Cost calculation of radiotherapy treatments at the multi-institutional level using Activity-Based Costing is feasible. SBRT shows larger variation in cost than more standardized radiotherapy approaches in line with the larger variability in technical solutions, time requirements and resource consumption. Its average cost however does not exceed the average cost of standard curative radiotherapy. Careful interpretation of these variables within the applicable economic context is required when using such cost data for determining financing levels.

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      MO17.08 - TCP modeling in Stereotactic Body Radiotherapy for early stage non small cell lung cancer: is a dose-volume effect present? (ID 2205)

      16:15 - 17:45  |  Author(s): H. Peulen, J. Belderbos, I. Grills, A. Hope, M. Guckenberger, M. Werner-Wasik, V.S. Mangona, Y. Xiao, A. Toussaint, D. Ionascu, J. Bissonnette, J.J. Sonke

      • Abstract
      • Presentation
      • Slides

      Background
      In early stage non-small cell lung cancer (NSCLC) stereotactic body radiotherapy (SBRT) has become standard of care for inoperable patients. Tumor size >3cm was reported to be a predictor of local recurrence (LR), suggesting a dose-volume effect. Recently, the dose effect relation was questioned[1]. We used a Tumor-Control-Probability (TCP) model on a large pooled multi-center cohort to test this.

      Methods
      850 patients were analyzed from our five institutes. Patients received a 4D CT-scan and plans were inversely optimized using advanced dose calculation algorithms. Treatment was delivered using online cone-beam CT guidance. Immobilization, margins, dose prescription and treatment planning was performed according to institute specific protocols. Median tumor diameter was 2.2 cm (range:0.7-8.0), median prescribed dose was 54 Gy (range:18-64) and median number of fractions were 3 (range:1-10). LRs were either biopsy proven or defined as a FDG-PET positive growing mass on CT-scan. The Web-Nahum TCP-model[2] was fitted to LR-data using maximum-likelihood estimation by optimizing its parameters: α representing the population-average radio-sensitivity, σ~α~ representing the population-variation in α and ρ the clonogen density. Input variables were the patient specific Gross Tumor Volume (estimated from the tumor diameter), for the dosimetric parameter PTV-D~min~, D~max~, D~mean~, D~1~, D~99~ were evaluated after conversion to Biological-Effective-Dose (BED) using the LQ-model with α/β=10Gy. We tested the optimized TCP model against a random model in which TCP was fixed independent of dose and volume. The optimal model was selected based on the Akaike-Information-Criterion (AIC).

      Results
      After a median follow up (FU) of 17 months (range:0-93), 43 LRs (5%) were diagnosed at 14 months FU (range:2-56), of which 25 tumors were biopsy proven and 18 recurrences diagnosed on PET-CT. The PTV-BED~mean~ based TCP model showed the best fit with parameters α=0.43Gy[-1] (CI:0.33–0.75) and σ~α~=0.17 Gy[-1] (CI:0.11–0.37). The model-fit was insensitive to ρ and set to literature values: 10[7]/cm[3]. The AIC of the optimal model was 12 units higher than the random model indicating a clear dose-volume-effect. At high PTV~mean~-BEDs, however, the volume effect is modest. Additionally, the AIC of the BED corrected model was 9.4 units higher than the BED uncorrected model. Figure 1

      Conclusion
      A dose-volume-effect relation in SBRT for early stage NSCLC for local control was derived in a large cohort of patients. This dose-effect relation requires validation in independent datasets and prospective trials. 1.van Baardwijk,Rad.Onc.,2012. 2.Web&Nahum,PMB,1993.

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      MO17.09 - Dosimetric Predictors of Esophageal Toxicity after Stereotactic Body Radiotherapy for Central Lung Tumors (ID 1674)

      16:15 - 17:45  |  Author(s): A. Modh, E. Williams, A. Rimner, A. Foster, E. Yorke, A. Jackson, A.J. Wu

      • Abstract
      • Presentation
      • Slides

      Background
      Stereotactic body radiotherapy (SBRT) is an effective treatment for early-stage non-small cell lung cancer (NSCLC) and lung metastases. However, increased toxicity has been observed for SBRT to lesions near the proximal airways or mediastinal structures. Reported toxicities have primarily pertained to pulmonary complications, but little is known about the risk for esophageal toxicity. Therefore, we sought to evaluate dosimetric predictors of esophageal toxicity in this patient cohort at our institution.

      Methods
      We identified 125 patients who received SBRT for single lung tumors within 2 cm of the proximal bronchial tree (n=81) or whose planning target volume (PTV) intersected mediastinal structures (n=44). Ninety-one patients had primary NSCLC, 12 had recurrent NSCLC, and 22 had metastatic tumors involving the lung. Patients with prior thoracic radiotherapy were excluded. Toxicity was scored using the Common Terminology Criteria for Adverse Events v.4.0. Biological equivalent doses (BED) were calculated using the linear quadratic formula with either α/β=3 or 10 Gy. Dose-volume histogram variables for the esophagus (D~v~, minimum dose to the hottest volume v and V~d~, volume receiving doses greater than d) were then examined for all patients and correlation with toxicity was assessed using logistic regression. Log rank tests were performed using median splits for variables that were significant in logistic regression.

      Results
      With a median follow-up of 14.3 months, the overall rate of grade ≥2 esophageal toxicity was 12.8% (n=16), including two grade 3 events. The median prescription dose was 45Gy. The most common fractionation schemes were 45Gy in 5 fractions (n=56), 48Gy in 4 fractions (n=21), or 50Gy in 5 fractions (n=14). Highly significant logistic models were generated on the basis of D~3.5cc~, D~5cc~, and D~max ~(p<0.001). For a complication rate < 20%, D~3.5cc~ ≤ 29.4 Gy~10~, D~5cc~ ≤ 25.4 Gy~10~, and D~max~ ≤ 50.1 Gy~10~ was observed based on these models (BED~10~). Log rank tests showed that at 2 years, the probability of complication of those with a BED~10~ D~3.5cc~ > 16.6 Gy was 25% (p<0.001), D~5cc~ > 15.1 Gy was 26% (p<0.001), and a D~max~ > 29.6 Gy was 21% (p=0.032). The probability of complication for those with a D~3.5cc~, D~5cc~, and D~max~ (BED~10~) less than or equal to the above limits were 2%, 2% and 7%, respectively. The analysis was insensitive to α/β, and the same D~v~ variables were found to be significant using α/β =3.

      Conclusion
      This is a novel quantitative analysis providing dose guidelines for significant esophagitis in the setting of SBRT. Dose to the hottest 3.5cc, 5cc and D~max~ were the best parameters for prediction of esophageal toxicity. Converting the BED~10~ limits to physical doses, D~3.5cc ~to the esophagus should be kept less than 18.3, 19.7 and 20.8 Gy for 3, 4, and 5 fractions, respectively, to keep the esophagitis rate < 20%. However, these guidelines must be weighed against clinical considerations and potential compromise of target coverage. This information will be valuable for treatment planning and identifying patients at risk for esophageal complications from SBRT.

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      MO17.10 - Late radiologic change after stereotactic ablative radiotherapy for early stage lung cancer: A comparison between fixed-beam versus arc delivery techniques (ID 1405)

      16:15 - 17:45  |  Author(s): S. Senthi, M. Dahele, P.M. Van De Ven, B.J. Slotman, S. Senan

      • Abstract
      • Presentation
      • Slides

      Background
      Treatment-related radiologic change occurs commonly following stereotactic ablative radiotherapy (SABR) and often confound the interpretation of follow-up CT scans. SABR is frequently delivered using both fixed-beams and rotational-arcs, resulting in different dose distributions and it is unclear how this influences radiological change. We studied the morphology, timing and severity of radiologic change after both delivery techniques.

      Methods
      Twenty-nine patients with early stage non-small cell lung cancer receiving SABR by arc delivery, without clinical evidence of local recurrence, and a follow-up of more than two years, were assessed using a published scoring system [Dahele M, JTO 2011]. Here, the morphology of acute (within six months) radiologic change was characterized between ‘patchy (less than 5 cm) ground glass opacity’, ‘patchy consolidation’, ‘diffuse (more than 5 cm) ground glass opacity’, or ‘diffuse consolidation’. The late (after 6 months) morphology was characterized between ‘scar-like’, ‘mass-like’ and ‘modified conventional’. Additionally the severity of radiologic change was scored as ‘pronounced’ (more than expected), ‘expected’, ‘mild’ (less than expected) and none. These outcomes were compared to 54 patients treated with SABR by fixed-beam delivery, who we previously assessed using the same scoring system.

      Results
      Baseline characteristics of the arc and fixed-beam cohorts were well matched and respective median follow-ups were no different, 31.7 vs. 28.4 months (p=0.20). Patients treated by arc delivery trended towards being more likely to have any radiologic change (p=0.06). This was strongly time-dependent (p<0.001) and more pronounced early, as by two years radiologic changes were almost universally present irrespective of delivery technique. Figure 1 shows the morphology of these changes with time. Acute changes were not technique dependent (p=0.23). After six months, arc delivery resulted in a modified-conventional morphology throughout follow-up, while fixed-beam delivery resulted in an increasing probability of scar-like or mass-like morphologies. The predicted probabilities of a modified-conventional pattern following SABR by arc and fixed-beam delivery were 96.3% vs. 68.9% (p<0.001) respectively. Following arc delivery, radiologic changes were more likely to be scored as pronounced or expected (p=0.009) than mild or none, a finding that became more evident with longer follow-up (p=0.014). The predicted probability of pronounced or expected changes two years following arc or fixed-beam delivery was 83.1% and 26.2%, respectively. Figure 1

      Conclusion
      Patterns of radiologic change more than six months post-SABR are influenced by delivery technique. Diagnostic algorithms used to differentiate suspected local recurrence and benign change should therefore consider the delivery technique used.

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      MO17.11 - Stereotactic ablative radiotherapy (SABR) for centrally located early-stage or isolated parenchymal recurrences of non-small cell lung cancer (NSCLC): How to fly in a "no fly zone" (ID 1961)

      16:15 - 17:45  |  Author(s): J.Y. Chang, Q. Xu, Q. Li, N. Rebueno, P. Balter, D. Gomez, R. Komaki, R. Mehran, S.G. Swisher, J. Roth

      • Abstract
      • Presentation
      • Slides

      Background
      SABR has become a standard treatment option for medically inoperable, peripherally located early-stage NSCLC. However, using SABR for centrally located lesions remains challenging because of the potential for severe side effects. Here we sought to validate our previous experience with SABR (50 Gy in 4 fractions) for central lesions, including the dose-volume constraints, and explore a new regimen of 70 Gy in 10 fractions for cases in which dose-volume constraints cannot be met with the previous regimen.

      Methods
      We used 4D-based, volumetric image-guided SABR to treat 101 patients with biopsy-proven and PET/CT-staged centrally located (within 2 cm of bronchial tree, trachea, major vessels, esophagus, heart, pericardium, brachial plexus or vertebral body) T1-2N0M0 tumors (n=82) or isolated lung-parenchyma recurrent lesions (n=19). The treatment period spanned February 2005 through May 2011; follow-up visits (every 3 months for 2 years and every 6 months for the next 3 years) included chest CT or PET/CT. Endpoints were toxicity (CTCAE v3.0), survival, local control, regional control, and distant metastasis.

      Results
      At a median follow-up time of 30.3 months for all patients (40.5 months for those alive), median overall survival time was 56.5 months and 5-year overall survival rate was 49.0%. Three-year actuarial local, regional, and distant control rates were 96.5%, 87.2% and 77.3%. The most common toxicities were chest-wall pain (18% grade 1 and 13% grade 2) and radiation pneumonitis (10.9% grade 2 and 1.9% grade 3). No patient experienced grade 4 toxicity and one patient with tumor invading bronchial tree who received 70 Gy in 10 fractions died from hemoptysis 13 months after SABR. The distance between tumor and chest was associated with chest wall pain (≤1 cm 45% vs >1 cm 17%, p=0.002). Univariate and multivariate analyses showed that for the 82 patients receiving 50 Gy in 4 fractions, mean total lung dose (MLD) >5 Gy or ipsilateral lung V~20~ (iV~20~) >16% were independent predictors of radiation pneumonitis; 3 of 9 patients in that group with D~max~ to brachial plexus >35 Gy experienced brachial neuropathy versus none of the 73 patients with brachial D~max~ ≤ 35 Gy (p=0.001).

      Conclusion
      SABR for centrally located lesions produces clinical outcomes similar to those for peripheral lesions when normal tissue constraints are respected. For 50 Gy in 4 fractions, we recommend MLD ≤5 Gy, lung iV~20~ ≤16%; bronchial tree D~max~ ≤ 38 Gy, V~35~ ≤1 cm[3]; major vessel D~max~≤ 56 Gy, V~40~≤1 cm[3]; esophageal D~max~ ≤35 Gy, V~30~≤1 cm[3 ]; brachial plexus D~max~ ≤35 Gy, V~30~≤0.2 cm[3] and spinal cord D~max~ <25 Gy. Giving 70 Gy in 10 fractions is another option for challenging cases but can produce severe toxicity if significant amounts of critical structures are exposed to ≥70 Gy. Proper selection of cases (based on tumor location and normal tissue constraints) and SABR regimens and volumetric image-guided delivery are all crucial to avoid overdosing critical structures. Typically, a minimum 5-10 mm distance between critical structures and gross tumor is required to meet dose-volume constraints.

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      MO17.12 - DISCUSSANT (ID 3934)

      16:15 - 17:45  |  Author(s): S. Yom

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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