Arbor, MI, 2Medical College of Georgia, Georgia Regents University,. Augusta, GA. Purpose/Objective(s): Despite the proven benefit of neoadjuvant che-.
Volume 90 Number 1S Supplement 2014
Oral Scientific Sessions
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Conclusions: We find a plasma microRNA panel that has considerable clinical value in diagnosing ESCC at an early stage of ESCC development. Thus, patients who would have otherwise missed the curative treatment window can benefit from the optimal therapy. Moreover, miR-16 can be a potential biomarker for evaluation of the efficacy of ESCC radiation therapy. Author Disclosure: Q. Yu: None. B. Li: None. S. Fu: None.
Conclusions: Neoadjuvant twice daily chemoradiation for esophageal cancer to 45 Gy is a safe and effective alternative to daily fractionation with low treatment related mortality and long term outcomes similar to standard fractionation. This regimen may be an effective alternative for patients requiring a shorter treatment time. Author Disclosure: S. Samuels: None. M.H. Stenmark: None. J.A. Hayman: None. M.B. Orringer: None. S.G. Urba: None. L. Sun: None. C. Xie: None. F. Kong: None. K. Cuneo: None.
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Neoadjuvant Twice Daily Chemoradiation Therapy for Esophageal Cancer: Treatment Related Mortality and Long-Term Outcomes S. Samuels,1 M.H. Stenmark,1 J.A. Hayman,1 M.B. Orringer,1 S.G. Urba,1 L. Sun,1 C. Xie,1 F. Kong,2 and K. Cuneo1; 1University of Michigan, Ann Arbor, MI, 2Medical College of Georgia, Georgia Regents University, Augusta, GA
Safety of Dose Escalation by Boosting Radiation Dose Within the Primary Tumor Using 18FDG-PET/CT for Unresectable Thoracic Esophageal Cancer W. Yu, X. Fu, X. Cai, Q. Liu, W. Feng, and Q. Zhang; Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
Purpose/Objective(s): Despite the proven benefit of neoadjuvant chemoradiation for esophageal cancer, patient outcomes remain poor. Due to the short potential doubling time of esophageal cancer, there is a theoretical benefit to using an accelerated radiation treatment schedule. For this study, we reviewed outcomes and treatment related mortality of patients treated in our institution with accelerated neoadjuvant chemoradiation. Materials/Methods: We analyzed outcomes for 250 consecutive patients with stage I-III esophageal cancer treated with preoperative hyperfractionated accelerated chemoradiation therapy (45 Gy in 30 BID fractions over 3 weeks) followed by planned transhiatal esophagectomy. Overall survival (OS) and locoregional control were determined using the Kaplan-Meier method. The log-rank test was used to determine statistical significance. This study was Institutional Review Board approved. Results: Median follow-up was 24 months for the entire cohort and 59 months for surviving patients. Eighty-six percent of patients had adenocarcinoma and 13% had squamous cell carcinoma. Clinical stage was I in 6%, II in 29%, and III in 65% of patients. Seventeen patients did not have surgery due to the development of metastases (n Z 15) or death (n Z 2). Ten patients were found to have unresectable and/or metastatic disease at the time of surgery. Overall, 6 patients (2.4%) died from treatment related causes and 3 month perioperative mortality was 3%. Median OS was 28.4 months for all patients and 34.2 months for patients who underwent esophagectomy. Pathologic stage (yp) was 0 in 16%, I in 21%, II in 27%, III in 34%, and IV in 3% of patients. Patients who had a pathologic complete response had a median OS of 120 months. Fiftythree percent of patients had pathologic down-staging after chemoradiation. Median OS for down-staged patients was 50.8 months vs. 16.9 months in patients with no down-staging (p < 0.001). Five year OS was 45% for patients with localized disease (ypN0) and 20% for patients with regional disease (ypN+). There were 32 isolated locoregional failures with a three year locoregional control rate of 83%. Concurrent chemotherapy included cisplatin, a taxane, or 5-FU in 86%, 80%, and 61% of patients, respectively. The use of a taxane or 5-FU did not affect survival (median OS 28.9 months vs. 28.4 months with and without taxane, p Z 0.36; median OS 29.9 months vs. 24.9 months with and without 5-FU, p Z 0.76).
Purpose/Objective(s): We designed this phase I trial (NCT01843049) to observe the safety of selective dose boost, using a simultaneous integrated boost (SIB) technique, to the high 18F-deoxyglucose (FDG) uptake areas of the esophageal GTV defined prior to the treatment. Materials/Methods: Patients with unresectable thoracic esophageal squamous cell carcinoma were included. Radiation dose was escalated at 4 levels with a minimum of 5 patients at each level. Doses given at PTV-G and PTV-C were 64 Gy/32 fractions (fx) and 50 Gy/25 fx for LEVEL 1 and 63 Gy/28 fx, and 50.4 Gy/28 fx for LEVEL 2. Doses given at PTV-GR (with an integrated boost to the 50% SUVmax area of the primary tumor of pre-treatment 18FDG-PET/CT scan), PTV-G and PTV-C were 70 Gy/28 fx, 63 Gy/28 fx and 50.4 Gy/28 fx for LEVEL 3 and 70 Gy/25 fx, 62.5 Gy/25 fx and 50 Gy/25 fx for LEVEL 4. Patients received 2 cycles of concurrent chemotherapy (cisplatin 25mg/m2 IV daily on Days 1-3 and 29-31 plus 5FU 500 mg/m2 IV continuous infusion over 24h daily on Days 1-4 and 2932) during radiotherapy period. Consolidation chemotherapy (cisplatin 25 mg/m2 IV daily on Days 1-3 plus 5-FU 600 mg/m2 IV daily on Days 1-5, cycled every 4 weeks) was given for 2 cycles one month after the end of radiochemotherapy. Toxicity was scored using RTOG Radiation Morbidity Scoring Criteria. Dose-limiting toxicity (DLT) was defined as any grade 3 or higher acute toxicity of lung, heart, and esophagus and grade 4 myelosuppression causing continuous interruption of radiation for over one week. Results: Accrual began in April 2012, and, so far, 25 patients have been enrolled onto this study. Radiation dose has been escalated up to LEVEL 4. All patients received prescribed radiation dose without continuous interruption of over one week and the first dose of concurrent chemotherapy. Despite of some delay, the second dose of concurrent chemotherapy was also completed successfully except 2 patients who were unable to tolerate the toxicity. For a variety of reasons, only 15 patients completed consolidation chemotherapy according to the protocol. During the period of concurrent treatment, 7 patients experienced grade 3 hematologic toxicity, 10 grade 3 esophagitis, and 6 grade 3 nausea and vomiting, but no DLT occurred. One of the first 5 patients at LEVEL 2 died of treatment-related esophageal hemorrhage within 3 months after the finish of radiotherapy; therefore, 5 additional patients were enrolled at this level. In addition, until
Oral Scientific Abstract 14; Table Summary of results Cases
Deviations
Middle 1/3 (n Z 28)
2 Major 6 Minor
Lower 1/3 (n Z 27)
6 Major 11 minor
GTV Analysis Range Median Interquartile range Range Median Interquartile range
Length (r-GTV Z 5.1 cm) 4.8-6.3 5.4 5.1-5.8 Length (r-GTV Z 6.9 cm) 4.2-9.9 6.9 6.2-7.3
Volume (r-GTV Z 14.8 cm3) 12.9-22.5 15.8 14.9-17.4 Volume (r-GTV Z 36.5 cm3) 25.0-63.6 33.0 31.1-38.2
JCI (r-GTV Z 1) 0.56-0.83 0.71 0.67-0.76 JCI (r-GTV Z 1) 0.40-0.83 0.71 0.64-0.78
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International Journal of Radiation Oncology Biology Physics
now, another 5 deaths were observed at other levels, all because of disease progression. Late toxicities remained under observation. Conclusions: Dose escalation in esophageal cancer has been safely achieved using SIB technique despite of difficulty in completion of consolidation chemotherapy. Acute toxicities of concurrent treatment were well tolerated and late toxicities deserved further observation. Author Disclosure: W. Yu: None. X. Fu: None. X. Cai: None. Q. Liu: None. W. Feng: None. Q. Zhang: None.
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15 Failure Patterns after Definitive Chemoradiation Therapy with Involved-Field Irradiation for Locally Advanced Esophageal Squamous Cell Carcinoma M. Li,1 X. Zhang,2 Z. Liao,3 X. Meng,4 L. Kong,4 X. Zhang,4 F. Shi,4 Y. Zhang,4 G. Wei,2 H. Man,1 G. Zhang,1 and J. Yu4; 1Shandong Cancer Hospital and Institute, Jinan, China, 2Shandong Cancer Hospital and Institute, Jinan, China, 3The University of Texas MD Anderson Cancer Center, Houston, TX, 4Shandong Cancer Hospital, Jinan Shandong 250117, China Purpose/Objective(s): Because locally advanced esophageal squamous cell carcinoma (ESCC) is associated with high local failure rates and poor survival, the need for potentially toxic elective nodal irradiation is controversial. The purpose of this study was to investigate failure patterns and survival in patients with locally advanced ESCC after receipt of definitive concurrent chemoradiation with involved-field irradiation (IFI). Materials/Methods: A retrospective study was performed on the clinical records of patients with locally advanced ESCC, who have received IFI with concurrent chemotherapy between January 2003 and January 2009. The target volume included the esophageal lesion and clinically malignant nodes. No prophylactic nodal irradiation was used. We compared target volumes and first sites of failure; failures were defined as in-field, out-offield regional nodes, and distant failure. Survival was analyzed according to patterns of failure. Results: Complete data were available for 80 patients. At a median follow-up time of 52.6 months, 76 patients (95%) had experienced failure (43 [54%] in-field, 24 [30%] out-of-field regional, and 33 [41%] distant). Overall survival differed significantly by in-field recurrence (median 14.2 months with vs.17.4 months without, P Z 0.01) and by distant failure (13.2 months with vs.15.9 months without, P 0.0001), but not by out-of-field regional lymph node failure (both 14.5 months, P Z 0.665). The failure rate of in-field alone, distant alone, and out-offield regional LN alone were 40%, 16.25%, and 12.5%, respectively. All of the 10 cases with solitary regional LN failure received salvage treatment and 4 of them experienced more than 24 months survival period. Conclusions: The predominant failure patterns after definitive chemoradiation with IFI for locally advanced ESCC were in-field and distant, and both negatively influenced survival. Having a solitary failure in an out-offield regional node did not influence survival. Further investigation is needed to establish the optimal radiotherapy fields for patients with advanced disease. Author Disclosure: M. Li: None. X. Zhang: None. Z. Liao: None. X. Meng: None. L. Kong: None. X. Zhang: None. F. Shi: None. Y. Zhang: None. G. Wei: None. H. Man: None. G. Zhang: None. J. Yu: None. Oral Scientific Abstract 15; Table
Prognostic Significance Of FDG-PET Metrics In Esophageal Squamous Cell Carcinoma A.M. Chhabra,1,2 L.T. Ong,1,3 D. Kuk,4 G. Ku,5 D. Ilson,5 Y.Y. Janjigian,5 A. Wu,2 H. Scho¨der,1,3 and K.A. Goodman1,2; 1Authors equally contributed to this paper, Memorial Sloan Kettering Cancer Center, NY, 2 Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 3Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 4Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, 5Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objectives: Fluorodeoxyglucose (FDG) avidity as measured by the maximum standard uptake value (SUV) at baseline and after induction chemotherapy (CT) on positron emission tomography (PET) imaging has been shown to be prognostic in patients with esophageal adenocarcinoma; however, the role of FDG PET in esophageal squamous cell carcinoma (SCC) has not been well established. We investigated the prognostic significance of various FDG metrics in a cohort of esophageal SCC patients treated with chemoradiation (CRT). Materials/Methods: We identified 58 esophageal SCC patients with fully analyzable FDG-PET data at baseline, post-induction CT and post-CRT. All patients received concurrent CRT, of which 53 patients also received induction CT and 11 patients underwent surgery following CRT. Median radiation dose was 5040 cGy (range 5040-5600 cGy). All scans were independently analyzed by a nuclear medicine physician blinded to patient outcome. Using region of interest analysis, max and mean standardized uptake value (SUVmax, SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated for the index lesion and nodes in each patient. Kaplan-Meier analysis was used to evaluate overall survival (OS), disease free survival (DFS), local recurrence free survival (LRFS), and distant metastasis free survival (DMFS). The log-rank test was used to assess correlation between outcomes and FDG-PET metrics. Results: Median follow-up was 3.8 years, with median survival for all patients of 2.9 years. The 3-year OS, DFS, DMFS, and LRFS rates were 49%, 47%, 43%, and 42%, respectively. Using a pre-established cutoff of a 35% decrease in SUVmax from baseline to post-induction PET, 3 yr OS for responders ( 35% decrease from baseline) was 52%, whereas nonresponders (< 35% decrease from baseline) had a 3 yr OS of 21% (p Z 0.046). Baseline SUVmax, SUVpeak, MTV, and TLG were significantly associated with OS, LRFS, DFS, and DMFS. On post-induction PET, SUVmax, SUVpeak, MTV, and TLG were significantly associated with OS, LRFS, DMFS, and DFS. After completion of CRT, only SUVmax was prognostic for OS, while only SUVmax and TLG were prognostic for DMFS. Conclusion: Baseline and post-induction PET metrics were most prognostic in patients with esophageal SCC. Our data confirms a 35% decrease in SUVmax after induction CT, as established in the adenocarcinoma literature, is also a significant predictor of OS in esophageal SCC patients. This analysis demonstrates that in addition to SUVmax, volumetric PET metrics may also be useful in predicting outcomes. Author Disclosure: A.M. Chhabra: None. L.T. Ong: None. D. Kuk: None. G. Ku: None. D. Ilson: None. Y.Y. Janjigian: None. A. Wu: None. H. Scho¨der: None. K.A. Goodman: None.
The Failure Patterns
Location of Failure
No. of Patients
In-field with or without others In-field alone Out-of-field with or without others Out-of-field alone Supraclavicular Mediastinal Celiac Distant with or without others Distant alone
43 32 24 10 3 3 4 33 13
17 Does Taxane-based Chemoradiation therapy Increase the Risk of Pneumonitis in the Treatment of Locally Advanced Esophageal Cancer? M.M. Dominello,1 T. Shaikh,2 M. Zaki,1 O. Zamen,1 N. Hurst,1 J. Martin,2 E. McSpadden,1 A. Shields,1 P. Phillip,1 J. Meyer,2 and A. Konski1; 1 Wayne State University, Detroit, MI, 2Fox Chase Cancer Center, Philadelphia, PA
