Treatment of Stage III Non-Small Cell Lung Cancer Patients With Concurrent Chemotherapy and Radiation (70 Gy): Equivalent or Superior to 60 or 74 Gy of RTOG 0617?

E428 between January 1980 and January 2010 was conducted. Patients who underwent complete resection were excluded. Data regarding demographics, histology, invasion, radiation therapy, chemotherapy and survival were collected. Survival time was calculated from the time of the diagnosis for new cases. Overall survival (OS) was calculated to the patient’s death. Local-regional free survival (LRFS) was calculated to the date of documented clinical local recurrence. Survival curves were plotted using the Kaplan-Meier method. The Log-Rank test was used for univariate analysis. The data was calculated by SPSS 20.0 software. Treatment toxicities were graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Results: Forty-seven patients was enrolled .Twenty-six patients received debulking surgery plus radiation therapy (DR) while 21 patients received radiation therapy alone (RT). The ECOG score were well balanced between the two groups (P Z 0.583). The median age was 55.5 years old and 54 years old in DR group and RT group. There were 19 (73.1%) and 11 (52.4%) males in DR and RT groups. Squamous cell carcinoma is the most common histological type in both groups. Great vessel invasion was observed in 76.9% and 76.2% in DR group and RT group respectively (P Z 0.960). Median radiation dose was 60Gy in both groups. Patients who received chemotherapy account for 53.8% and 47.6% in DR group and RT group (P Z 0.671). Five-year overall survival of the DR group and RT group were 54.4% and 13.1% (P Z 0.019), while 5-year LRFS of the DR group and RT group were 95.7% and 73.7% (P Z 0.010). No operation induced mortality was recorded. Two patients were diagnosed with Grade 2 radiation induced pneumonitis and 2 patients were diagnosed with Grade 3 radiation induced esophagitis, all of which was in RT group. Conclusion: For patients with unresectable Masaoka stage III disease, debulking surgery with radiation therapy is a preferable choice compared with radiation alone. Author Disclosure: Y. Zhai: None. W. Ji: None. Z. Hui: None. X. Wang: None. J. Liang: None. J. Lv: None. H. Zhang: None. Q. Feng: None. Z. Zhou: None. C. Dongfu: None. L. Wang: None.

3054 Early Cardiotoxicity in Thoracic Radiation Therapy for Lung and Esophageal Cancer J. Borkenhagen,1 C. Rapp,1 S. Klawikowski,1 L.E. Rein,1 and E.M. Gore2; 1 Medical College of Wisconsin, Milwaukee, WI, 2Medical College of Wisconsin and Clement J. Zablocki VA Medical Center Department of Radiation Oncology, Milwaukee, WI Purpose/Objective(s): To determine the frequency of cardiotoxicity and the spectrum of cardiac events observed during or shortly following radiation therapy (RT) to the thorax. RTOG 0617 unexpectedly showed lower median survival with high dose (74 Gy) vs standard dose (60 Gy) RT for stage III lung cancer. Heart V5 and V30 were among the factors predicting survival, although there was no severe cardiac toxicity reported. We hypothesize that cardiac events are more common than currently appreciated in the period during and shortly after RT for lung and esophageal cancers (LEC). Materials/Methods: We retrospectively reviewed charts of 100 patients receiving thoracic RT for LEC in our department from 2012-2015. Cardiac events were identified by review of notes, imaging, EKGs, and echocardiograms. Only new diagnoses after the start of RT were considered. Medically significant cardiac events were defined as those requiring intervention. Kaplan-Meier analysis was used to estimate event-free survival for each category of cardiac event. Results: The number of medically significant cardiac events observed in the first few years following thoracic RT was 10. Median follow-up was 1 year (range 0.2-3.3 years). The number of patients with any new cardiac pathology was 32. Medically significant events observed included 1 large pericardial effusion which responded to treatment with colchicine and 9 new atrial arrhythmias. The number of patients developing atrial arrhythmias was 6/73 in the lung cancer group and 3/27 in the esophageal cancer group. Three of the 9 patients were diagnosed during treatment; the rest were diagnosed from 5-87 weeks following completion of RT.

International Journal of Radiation Oncology  Biology  Physics Abstract 3054; Table 1. New Cardiac Pathologies Observed During and Following RT. Event New Atrial Arrhythmia Trace Pericardial Effusion Small to Moderate Pericardial Effusion Large Pericardial Effusion New or Progressed Valve Disease Right Bundle Branch Block

Number Kaplan-Meier Event-Free Survival (% at 1 Observed year, confidence interval) 9 8

92 [87, 98] 92 [86, 99]

13

89 [82, 96]

1

99 [96, 100]

3

96 [91, 100]

2

98 [95, 100]

Conclusion: Although classically cardiotoxicity of thoracic RT occurs years following treatment, our data demonstrate that cardiac events occur during treatment and in the early post-treatment period for patients receiving thoracic RT for LEC. The majority of medically significant cardiac events observed were new-onset atrial arrhythmias. It is possible that patients with early cardiac events, even clinically insignificant ones, are at increased risk for late cardiac toxicity. Further research is needed to examine the utility of screening patients pre- and post- thoracic RT for cardiac health. In light of our findings and those of RTOG 0617, further investigation into dosimetric parameters predicting cardiotoxicity in thoracic RT for LEC is also warranted. Author Disclosure: J. Borkenhagen: None. C. Rapp: None. S. Klawikowski: Employee; Green Bay Oncology. L.E. Rein: None. E.M. Gore: Employee; Medical College of Wisconsin.

3055 Treatment of Stage III Non-Small Cell Lung Cancer Patients With Concurrent Chemotherapy and Radiation (70 Gy): Equivalent or Superior to 60 or 74 Gy of RTOG 0617? G.D. Grass, A.O. Naghavi, J.M. Frakes, B.A. Perez, and T.J. Dilling; Lee Moffitt Cancer Center and Research Institute, Tampa, FL Purpose/Objective(s): RTOG 0617 demonstrated inferior outcomes with 74 Gy of concurrent radiation (RT) and chemotherapy (CT) compared to 60 Gy, though the findings are controversial. We hypothesized that an intermediate RT dose might reach equipoise and improve outcomes versus 60 Gy or 74 Gy. This retrospective single institution analysis analyzed patients treated uniformly with 70 Gy/concurrent CT. Materials/Methods: Records from 216 consecutive patients with Stage III NSCLC treated from 2000 to 2015 with concurrent CT and RT (70 Gy) were reviewed. Patient demographics, tumor/treatment details and outcomes were abstracted. Local failure (LF), regional failure (RF), distant failure (DF), disease-free survival (DFS) and overall survival (OS) were estimated using Kaplan-Meier univariate (UVA) and Cox-regression multivariate (MVA) analyses. Predictors of toxicity were evaluated by Pearson Chi-Square. Results: Median follow-up was 18 months. Median age was 63 years; 53% were female. Histology: adenocarcinoma (49%), squamous cell carcinoma (32%), other (19%). Patients were mostly stage IIIB (50.4%), T3/T4 (53.7%), N2 (64%) and N3 (28%), and were ECOG 0 (33%), 1 (56%), and 2 (11%) at diagnosis. CT included platinum doublets (94%), weekly (52%), induction (12%) and consolidative (22%) therapy. Median OS was 26 months and 2-yr survival was 58.1%. The 2-yr OS for IIIA and IIIB patients was 61.8% and 42.4%, respectively. The overall 2-yr LF, RF, and DF rates were 30.4%, 32.9% and 54.9%, respectively. 2-yr DFS was 28.8%. In UVA, ECOG predicted for LF (P Z 0.004) and RF (P Z 0.006). DF was associated with N stage (N0/1/2 vs. N3; P Z 0.013), ECOG (P Z 0.03) and IIIA vs. IIIB (P Z 0.011). N stage (P Z 0.041), ECOG (P Z 0.0001) and overall stage (P Z 0.007) were predictive of DFS. Stage (P Z 0.003) and ECOG (P Z 0.002) predicted for improved OS. ECOG was significant on MVA for LF, RF, DF, DFS and OS, while N stage was predictive for RF, DF, DFS and OS. Toxicity was manageable: 10.6% had Grade 3 esophagitis and 15.7% and 1.9% had Grade 2 or 3 pneumonitis with no Grade 4/5 events. Esophageal ulceration and dilation rates were

Volume 96  Number 2S  Supplement 2016 16.2% and 10.6%, respectively. Esophagitis grade was predictive of ulceration (P Z 0.0001) or dilation (P Z 0.0001). N stage (P Z 0.008) and overall stage (P Z 0.022) were predictive of pneumonitis grade. Conclusion: Patients in our cohort were frailer and had more advanced disease than the 0617 patients. Despite this, we demonstrate that CT with an intermediate RT dose of 70 Gy leads to better outcomes than the 74 Gy arm in RTOG 0617 with less esophageal toxicity. Preliminary analysis suggests that omission of ECOG-2 patients leads to superior outcomes for 70 Gy compared with the 60 Gy patients in 0617; analysis is ongoing. ECOG was a major determinant of survival outcomes. Author Disclosure: G.D. Grass: None. A.O. Naghavi: None. J.M. Frakes: None. B.A. Perez: None. T.J. Dilling: None.

3056 Lymph Node Drainage Patterns in Resectable Non-Small Cell Lung Cancer and Its Clinical Significance G. Lin, Z. Wang, X. Sun, J. Liu, and Y. Xu; Zhejiang Cancer Hospital, Hangzhou, China Purpose/Objective(s): Our study aimed at analyzing the characteristics of regional lymph node metastasis in patients with resectable non-small cell lung cancer (NSCLC) and assessing its significance in surgical mediastinal lymph dissection and the target volume definition of postoperative radiation therapy. Materials/Methods: We retrospectively reviewed 810 patients with NSCLC, and the metastatic frequency of each regional lymph node station was analyzed as well as the correlation between tumor location and regional lymph node metastases. Results: A total of 2315 groups of lymph nodes were removed. Pathology results showed that lymph node metastasis appeared in 550 groups. Regional lymph nodes metastases were significantly associated with age, histology, tumor size and tumor location (P Z 0.013, 0.000, 0.009 and 0.000, respectively). The prior location of involved regional lymph nodes in different lobes of patients with NSCLC were as follows: The 2-4 station for right upper lobe tumors; the 2-4 and 7 station for right middle lobe tumors and right lower lobe tumors; the 5-6 station for left upper lobe tumors; the 5-6 and 7 station for left lower lobe tumors. Conclusion: The younger patients with left lung adenocarcinomas and large tumor size tended to regional lymph node metastases. The trend of regional lymphatic drainage in lobes of lung occurred differently. We should pay more attention to regions regarding the higher frequencies of lymph node metastases, when determining the extent of lymph node dissection or delineating the target volume of postoperative radiation therapy for NSCLC patients. Author Disclosure: G. Lin: None. Z. Wang: None. X. Sun: None. J. Liu: None. Y. Xu: None.

3057 Focal Radiation Therapy for Pleural Dissemination of Thymic Tumors D. Okazaki,1 K. Tatekawa,2 K. Uchiyama,3 C. Hashizume,4 Y. Manabe,5 Y. Ogawa,5 C. Sugie,1 T. Yanagi,5 and Y. Shibamoto5; 1Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, 2Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan, 3Department of Radiology, Nagoya Daini Red Cross Hospital, Nagoya, Japan, 4Nagoya Radiosurgery Center, Nagoya Kyoritsu Hospital, Nagoya, Japan, 5 Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Purpose/Objective(s): Pleural dissemination is a common pattern of failure after treatment of invasive thymoma and thymic cancer. Since lesions of pleural dissemination are usually multiple, radiation therapy has never played an important role in their treatment. Chemotherapy may be a reasonable treatment option for these lesions, but no efficient regimens have been established in the treatment of pleural dissemination. Since thymic tumors are relatively radiosensitive and they often show insidious progression, we hypothesized that focal radiation should play a role in

Poster Viewing E429 controlling the lesion and possibly improving prognosis of the patients. In this study, we evaluated the treatment outcome of 40 lesions of pleural dissemination. Materials/Methods: From 2004 to 2015, 40 lesions of pleural dissemination in 13 patients after initial treatment for invasive thymoma or thymic cancer were treated with radiation therapy in our institution. Cases treated merely with palliative intent were excluded. Seven of the 13 patients were men and 6 were women. Their median age was 60 years (range, 32-81 years). The Masaoka stage at initial presentation was III in 6, IVa in 6, and IVb in 1. The WHO histology was A in 1, B1 in 1, B2 in 5, B3 in 3, AB in 1, C (squamous cell cancer) in 1 and unknown invasive thymoma in 1. The mean diameter of pleural nodules was 20 mm (range, 6-56 mm). As an initial therapy for thymic tumors, 12 of the 13 patients had undergone surgical resection, and 10 had received mediastinal irradiation. All lesions were irradiated to the nodule plus about 1-cm margins. In addition to the focal irradiation, one patient received hemithoracic irradiation with 15 Gy in 10 fractions. Two of the 13 patients having 5 and 14 lesions, respectively, were treated with intensity-modulated radiation therapy (IMRT) using tomotherapy. The median total radiation dose to the nodules was 50 Gy (range, 36-60 Gy). All patients were followed with CT. Survival and local control rates were calculated by the Kaplan-Meier method. Results: Median follow-up period after the first irradiation for pleural dissemination was 29 months (range, 5-113 months). Thirty-three lesions showed a complete response and 5 lesions had a partial response. Only 2 lesions showed regrowth at 8 and 108 months, respectively, after irradiation. At 3 years, the local control rate was 98% and overall survival rate was 92%. Grade 3 toxicity (pericardial effusion) was observed in one patient. Other toxicities were all grade 2 (dermatitis in one patient) or lower including patients treated to many sites with IMRT. Conclusion: Focal radiation therapy appears to play an important role in local control of pleural dissemination from thymic tumors. It might also prolong survival time. When disseminated nodules can be covered with a single radiation field, the use of radiation therapy might be a treatment option. With IMRT, multiple sites could be treated safely. Author Disclosure: D. Okazaki: None. K. Tatekawa: None. K. Uchiyama: None. C. Hashizume: None. Y. Manabe: None. Y. Ogawa: None. C. Sugie: None. T. Yanagi: None. Y. Shibamoto: None.

3058 Risk Factors for Early Radiation-Induced Cardiotoxicity in Lung and Esophageal Cancer C. Rapp,1 J. Borkenhagen,1 S. Klawikowski,1 L.E. Rein,1 and E.M. Gore2; 1 Medical College of Wisconsin, Milwaukee, WI, 2Medical College of Wisconsin and Clement J. Zablocki VA Medical Center Department of Radiation Oncology, Milwaukee, WI Purpose/Objective(s): The primary objective of this analysis is to determine the risk factors for early cardiac toxicity associated with radiation therapy to the thorax. Although the late cardiovascular effects of radiation are appreciated as a serious and life threatening complication in long term cancer survivors who have received thoracic radiation, the early effects are not as well characterized. Materials/Methods: We retrospectively reviewed charts of 100 patients who received thoracic RT for lung or esophageal cancer with > 45 Gy at our institution from 2012-2015. Pre- and post-RT cardiac disease was evaluated by review of available notes, imaging, EKGs, and ECHOs. Univariate analysis with Cox PH regression modeling was used to evaluate association between cardiotoxicity and histology, esophageal vs. lung primary, gender, and history of hypertension (HTN), diabetes mellitus (DM), tobacco use, and peripheral vascular disease (PVD). Results: Of the 100 patients, 73 were treated for lung cancer and 27 for esophageal. 83 received chemotherapy in addition to RT. Radiation median dose [min, max] for lung cancer was 60 Gy [44, 69] and for esophageal cancer was 50 Gy [50, 60]. Median follow-up was 1 year with a range of 2 to 40 months. A total of 32 patients had at least 1 cardiac event. Time to event ranged from 19 days prior to RT completion to 22 months post RT. Events included new pericardial effusion (n Z 22), new arrhythmia (n Z 9), new