II NSCLC

Volume 87  Number 2S  Supplement 2013

Poster Viewing Abstracts S543

Poster Viewing Abstract 2890; Table

Day 0

Days 16 vs 0 Days 31 vs 0

3DC free 3DC DIBH VMAT DIBH 3DC DIBH vs free VMAT DIBH vs 3DC free 3DC VMAT 3DC VMAT

MLD

V5

V20

V40

17.3  6.6 Gy 14.7  5.9 Gy 14.0  5.5 Gy 15.6% * 19.3% * 0.6% 1.1% 0.8% 3.3%

51.0  23.6% 45.5  22.4  57.3  25.2% 14.2% * 11.2% * 0.8% 0.1% 1.6% 0.1%

29.0  12.2  24.9  11.0% 24.2  11.0% 14.8% * 17.9%* 0.3% 0.3% 1.1% 0.5%

18.4  6.8% 15.6  6.1% 10.3  4.1% 15.5% * 44.5%* 3.8% 3.5% 0.5% 2.9%

Purpose/Objective(s): Radiation therapy (RT) of lung cancer results in poor survival and high lung toxicity. RT in deep inspiration breath hold (DIBH) has the potential for reducing lung toxicity as lung volume increases. Prior to clinical implementation, evaluation of voluntary DIBH feasibility and reproducibility throughout the treatment course is necessary. Materials/Methods: Ten patients with locally advanced lung cancer entered the study so far. Besides standard imaging for RT planning (4D CT and DIBH CT) 6 patients were also scanned in DIBH at treatment days 16 and 31. Voluntary DIBH were visually guided to a comfortable level with a gating window of 2-3 mm, adjusted to each patient. Respiration was monitored with an optical marker based system. The patients’ capability to increase lung volume and to perform repeated DIBH lasting 20 seconds or more throughout the RT course was considered a measure of feasibility. The 3D conformal (3DC) and Volumetric Modulated Arc Therapy (VMAT) treatment plans were calculated on planning day’s DIBH (DIBHday0) to deliver 66 Gy in 33 fractions. 3DC plan used the same field angles as the clinical free breathing plan. VMAT used 2 full or partial arcs, depending on anatomy. DIBH CT from days 16 and 31 were registered to DIBHday0 with tumor registration. RT plans optimized on DIBHday0 were applied to DIBH from days 16 and 31. Plans were compared on lung parameters V5, V20, V40, mean lung dose (MLD) and target coverage. Results: Lung volume increased in DIBH by 57% (range, 35-87%; p < 0.0001; paired t-test). All patients could perform at least 6 consecutive DIBH lasting over 20 s throughout the treatment course. 3DC plans were planned with 3-5 fields, requiring 3-5 DIBH pr treatment fraction. 8/10 VMAT plans were planned with 2 partial arcs, requiring 4 DIBH pr treatment fraction, 2 full arcs would require 6 DIBH. Lung parameters were significantly reduced in DIBH with both 3DC and VMAT (except V5 in VMAT) with same or better target coverage. Treatment plans applied on DIBH scans from days 16 and 31 showed small non-significant changes of a few % in both lung and target. Data is presented in table as mean  SD or mean and marked with * if statistically significant at 0.05 level. Conclusions: DIBH is feasible, well tolerated and gives considerable lung inflation (>50%). Both 3DC and VMAT plans are robust to anatomy changes during a RT course. We are continuously accruing more patients in the protocol in order to strengthen these encouraging early results on feasibility of visually guided voluntary DIBH RT. Author Disclosure: M. Josipovic: None. G.F. Persson: None. K. Ha˚kansson: None. S. Damkjær: None. G. Westman: None. J. Bangsgaard: None. L. Specht: None. M. Aznar: None.

2891 Experience in Stereotactic Radiation Therapy for Lung Cancer L. Larrea, E. LopezMun˜oz, P. Antonini, J. Bea, M. Ban˜os, and M. Garcia; Hospital NISA Virgen del Consuelo, Valencia, Spain Purpose/Objective(s): To review our institution’s last decade experience in patients with medically inoperable lung tumors treated with stereotactic body radiation therapy (SBRT) in terms of local control and survival.

Materials/Methods: Between 2002 and 2012, 112 consecutive patients with 125 lung tumors were treated using SBRT. Those tumors included: lung cancers of any histology (75.2%), metastatic lung nodules (14.4%) or solitary pulmonary nodules suspicious of malignancy with no pathological confirmation (10.4%). Treatment outcomes, toxicity and technique were analyzed retrospectively. SBRT involved: (1) Computed tomography (CT) slow-scan simulation with immobilization devices, (2) contouring the target volume in 3 sets of CTs, (3) superimposing the volumes in the planning system to represent the internal target volume (ITV), (4) dose calculation using heterogeneity correction and assuring very conformal dose distribution and a steep fall-off of the radiation dose outside treatment volume and (5) radiation delivery with multiple static non-coplanar non-opposing beams and arc therapy. The prescribed dose was either 3 fractions of 14-16 Gy each or a single 30-Gy fraction (corresponding to biologically equivalent doses >100). Dose constraints were set for spinal cord and lung volume. Toxicity and radiologic response were assessed in follow-up visits, using conventional criteria (RTOG, EORTC scores and radiologist reviewed reports). Survival rates and cumulative incidences of toxicities were calculated by the KaplanMeier method. Results: Median patient age was 69.3 years (47-86). Mean tumor volume was 6.62 cm3 (0.6-292.7). Acute toxicities were grade 1 or 2 esophagitis, pneumonitis or dermatitis and occurred in 9.6% of all cases. No toxicities grades >3 were identified. The median follow-up was 18 months (3-65). The 2-year survival was 69% for all patients and 75.2% for primary tumors. Local control in the irradiated volume is 95.7%. Conclusions: SBRT is an excellent treatment option for primary or metastatic lung tumors. Our encouraging results in terms of survival, local control and toxicity are in line with those previously reported in recent literature. Author Disclosure: L. Larrea: None. E. LopezMun˜oz: None. P. Antonini: None. J. Bea: None. M. Ban˜os: None. M. Garcia: None.

2892 Salvage Radiation for Mediastinal Relapse After Treatment With Accelerated Hypofractionated Radiation Therapy (AHRT) or Stereotactic Body Radiation Therapy (SBRT) for Stage I/II NSCLC S.C. Lester, J.M. Kilburn, J.T. Lucas, M.T. Munley, A.W. Blackstock, W.T. Kearns, W.H. Hinson, A.A. Miller, W.J. Petty, and J.J. Urbanic; Wake Forest Baptist Health, Winston-Salem, NC Purpose/Objective(s): Regional failures occur in up to 15% of patients (pts) treated with definitive radiation therapy for Stage I/II NSCLC. Limited data exists on the outcome of patients with mediastinal failure after SBRT or AHRT. We present our experience of salvage radiation therapy for mediastinal recurrences after AHRT or SBRT in stage I and II NSCLC. Materials/Methods: All pts treated (rx) with SBRT or AHRT for stage I/II NSCLC were screened for treatment of isolated mediastinal failures (IMF). Pts were included if treated with mediastinal radiation therapy (MRT) and intent was curative. MRT was 3DCRT or IMRT. Prior to 2007, 10 mm PTVexpansions to GTV were applied. No elective nodal coverage was used. A 4D CT derived ITV and 5 mm PTV was used after 2007. Pt failures

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International Journal of Radiation Oncology  Biology  Physics

were scored as local (at SBRT/AHRT site or same lobe), regional (nodal disease in hilum/mediastinum), or distant. Toxicity was per NCI CTCAE v4.0. Local Control (LC), Regional failure (RF), Progression Free Survival (PFS), and Distant Failure (DF) were estimated from the date of MRT using the Kaplan Meier method. The composite plans and DVH were available for 10 of 12 pts. Results: Approximately 300 Stage I/II NSCLC pts rx with SBRT/AHRT were screened (2002-2012), 12 suffered IMF and tx with salvage MRT. Original primary tumor treated: SBRT (10 pts), AHRT (1 pt) and AHRT/SBRT (1 pt bilateral stage I). Average tumor size at dx: 1.5 cm (0.7-2.8 cm). Stage was IA in 9 pts, Stage IIA 1 pt, and Stage IIB 2 pts. Median age was 64 yrs. Median dose for initial course: SBRT 54 Gy, 3 fx (45-60 Gy), AHRT 70.2 Gy, 26 fx. Median interval between initial rx and MRT: 16 m (2-57 m). Median MRT dose: 66 Gy 2.0 Gy/fx (60-70 Gy). 2 pts received concurrent chemo with MRT. Composite lung V20 was 25% (13-29%). Median follow-up was 11 m (2-49 m). 2 yr OS was 29% with median OS of 15 m (95% CI 5.8-37 m). 2 yr PFS was 37% with a median of 14 m (95% CI 5-49 m). When estimated from original rx with SBRT or AHRT, 2 yr OS was 78% with a median OS of 38 m (95% CI 17 m-NR). No subsequent RF occurred after MRT. LC was established in 11 of 12 pts. DF was the predominant mode of failure (5/ 12 pts) with a 2 yr DF rate of 62%. 3 pts died without recurrence, 4 pts alive and NED. MRT toxicity was seen in 3 pts (grade 2 acute). 2 pts experienced late toxicity with 1 requiring supplemental oxygen and 1 with sustained dysphagia. Conclusions: To our knowledge this is first analysis of MRT for salvage after SBRT or AHRT for NSCLC. Local-regional control was excellent. Outcomes for stage I/II pts with IMF were similar to Stage 3 disease with a median OS of 15 m. Distant failures were common, suggesting a role for concurrent or sequential chemotherapy. As the pattern of failure in early stage lung cancer has shifted from local to regional and distant recurrences, additional study of salvage therapies is needed. Author Disclosure: S.C. Lester: None. J.M. Kilburn: None. J.T. Lucas: None. M.T. Munley: None. A.W. Blackstock: None. W.T. Kearns: None. W.H. Hinson: None. A.A. Miller: None. W.J. Petty: None. J.J. Urbanic: None.

with SLR-B over SBRT, which would require a larger sample size to confirm. Our study supports the importance of enrollment to RTOG 1021 prospectively comparing these techniques. Author Disclosure: M. Manning: G. Consultant; GE. B. Sintay: None. D. Wiant: None. P. Ganem: None. J.S. Moody: None.

2893 An Overall Survival Comparison of Sub-Lobar Resection With Brachytherapy Versus Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer M. Manning,1 B. Sintay,1 D. Wiant,1 P. Ganem,2 and J.S. Moody1; 1Cone Health, Greensboro, NC, 2University of North Carolina-Chapel Hill, Chapel Hill, NC Purpose/Objective(s): Patients with early stage non-small cell lung cancer (NSCLC) who are unable to tolerate lobectomy may be candidates for sub-lobar resection with brachytherapy (SLR-B) or stereotactic body radiation therapy (SBRT). The superiority of either approach has not been confirmed. This IRB-approved retrospective study compares the overall survival of contemporaneous cohorts of patients receiving either SLR-B or SBRT. Materials/Methods: The study subjects had clinical stage I NSCLC based on PET-CT staging and were considered ineligible for lobectomy. From 2006 through 2011, 56 underwent SLR-B and 47 underwent stereotactic body radiation therapy. The brachytherapy implants consisted of customized absorbable polyglactin knitted mesh containing a median of 40 (3050) Iodine-125 seeds with a median seed activity of 0.536 mCi and total median implant activity of 21.44 mCi. The stereotactic body radiation therapy patients underwent 4-dimensional CT image planning and treatment using 3 or 5 fractions to 54 or 50 Gy. Results: The median tumor sizes were 1.6 cm and 2.0 cm in the SLR-B and SBRT groups, respectively. The median follow-up is 32 months. At 3 years the Kaplan-Meier actuarial overall survivals are 71% and 61% in the SLR-B and SBRT groups, respectively (p Z 0.3). Conclusions: SLR-B and SBRT appear to provide acceptable survival outcomes. This retrospective study hints at a potential superior survival

2894 Inhibition of Aurora A Increases Sensitivity to Radiation Therapy in Selected Lung Cancer Cell Lines C. Myers,1 N. Liu,1 J. Ecsedy,2 and B. Lu1; 1Thomas Jefferson University, Philadelphia, PA, 2Millenium Pharmaceuticals, Philadelphia, PA Purpose/Objective(s): Aurora A, a serine-threonine kinase, is critical for the proper normal progression into and through mitosis. Aurora A overexpression has been noted in many tumors, and has been implicated in the development of resistance to chemotherapy. Previous research has suggested that Aurora A inhibition may increase cell sensitivity to radiation therapy (RT), and may act synergistically to overcome radiation therapy resistance. Materials/Methods: Three lung cell cancer lines of varying resistance to RT (lowest to highest, H2429, H460, H1299) were exposed to increasing concentrations (0, 6.25nM, 12.5nM, 25nM, 50nM, 100nM, 500nM, 1000nM) of the investigational Aurora A inhibitor MLN8237 (Alisertib). Both cell survival and Aurora A phosphorylation were assessed 24, 48, 72 and 96h after treatment; clonogenic assays were performed at the determined MLN8237 survival IC50. The change in effect of 2, 4, or 6 Gy of radiation, applied 2h after addition of the drug, was assessed at 48h. The role of p53 in the drug sensitivity was further investigated in a tet-inducible p53 system established in H1299 cells, which are naturally deficient in p53. Expression levels of p53, p21, cleaved caspase 3 and cleaved PARP were assessed 48h after irradiation. Results: Growth in all three cell lines (H2429, H460, H1299) was inhibited by MLN8237 (IC50 [48h] Z 100 nM, 100 nM, 500 nM, respectively). Phosphorylation of Aurora A was inhibited in a concentration-dependent manner. Incubation with MLN8237 further sensitized H460 and H2429 cell lines to RT, but had little effect on the growth of radiationresistant H1299 cells until activation of the tet-on p53 induction system, at which point growth was greatly inhibited. Caspase 3 and PARP cleavage were induced in a p53-dependent manner in H2429 and H460 cells. Levels of p53 and p21 were increased when tumor cells were treated with MLN8237. Induction of wild type p53 expression in H1299 cells using a tet-on system showed enhanced cell death via apoptosis, indicating that the inhibition of cell viability and radiosensitization were partly due to p53. Conclusions: Commonly studied lung cancer cell lines were found to have different sensitivities to Aurora A inhibition. Combining Aurora A inhibition with RT decreased cell survival in a p53-dependent manner. Exploration of the mechanisms of cell survival affected by Aurora A inhibition and characterization of the synergism between it and RT may offer new treatment opportunities for RT-resistant lung cancer. Author Disclosure: C. Myers: None. N. Liu: None. J. Ecsedy: A. Employee; Millenium Pharmaceuticals. B. Lu: None.

2895 Predictors of Symptomatic Radiation Pneumonitis (SRP) in Lung Cancer Patients Treated With Hypofractionated Radiation Therapy (H-RT) T. Lewis,1 J. Kim,2 B. Yue,2 M. Demarco,2 C.W. Stevens,2 and T.J. Dilling2; 1University of Southern Florida Morsani College of Medicine, Tampa, FL, 2Moffitt Cancer Center, Tampa, FL Purpose/Objective(s): H-RT is an effective and commonly-employed palliative regimen for many lung cancers. One prior publication of H-RT reported a SRP rate of 11.8%. Thus our objective was to define clinical and dosimetric factors predictive of SRP in patients receiving H-RT. Materials/Methods: We retrospectively evaluated 134 patients treated to the thorax to a total dose of 4500 cGy in 15 fractions of 300 cGy. Toxicity