Gastrointestinal Cancer

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SU_10_2102 - Predictors of Cardiac Toxicity in Operable Esophageal Cancer Patients Treated With or Without Chemoradiation.

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Predictors of Cardiac Toxicity in Operable Esophageal Cancer Patients Treated With or Without Chemoradiation.
J. S. Witt1, J. C. Jagodinsky2, Y. Liu3, P. Yadav1, A. Kuczmarska-Haas1, J. D. Maloney4, M. Yu3, M. A. Ritter1, M. F. Bassetti1, and A. M. Baschnagel1; 1Department of Human Oncology, University of Wisconsin Hospital and Clinics, Madison, WI, 2University of Wisconsin School of Medicine and Public Health, Madison, WI, 3Department of Statistics, University of Wisconsin School of Medicine and Public Health, Madison, WI, 4University of Wisconsin, Department of Cardiothoracic Surgery, Madison, WI

Purpose/Objective(s): To evaluate predictors of cardiac events in esophageal cancer patients treated with neoadjuvant chemoradiation followed by surgery (NA CRT) compared with a cohort of patients treated with surgery alone.

Materials/Methods: We retrospectively identified patients treated for esophageal cancer between January of 2006 and March of 2016. A total of 123 patients were identified; 70 were treated with surgery alone, and 53 were treated with NA CRT. Patients who died <1 month following treatment were excluded, as were patients with upper third esophageal tumors. Cardiac events were scored based on CTCAE v 4.03. Dosimetric data was compiled for all patients who received radiation. Univariate (UVA) and multivariable (MVA) analyses were performed to identify predictors of cardiac events. A competing risks regression analysis was performed (Fine and Gray method) to model the cumulative incidence of cardiac events.

Results: Patients in the surgery arm were younger (p = 0.01), had lower ECOG scores (p = 0.03), and lower clinical stage (p = 0.01), than patients who underwent NA CRT. The majority (83%) of the NA CRT patients received a dose of 50.4 Gy (range, 41.4 – 54 Gy). The majority (68%) of these patients were treated with 3D conformal radiation. The overall rates of grade ≥3 cardiac toxicity were 24.5% in the NA CRT group compared with 10% in the surgery group (p = 0.04). The median time to grade ≥3 event was 3.7 months in the NA CRT group compared with 1.7 months in the surgery alone group. The maximum ≥3 grade events included: 5 acute coronary syndromes, 2 new diagnoses of congestive heart failure, 8 arrhythmias, 1 cardiac arrest, 3 pericardial effusions, and 1 pericarditis. Both NA CRT (p = 0.04, HR 2.56, 95% CI 1.06 - 6.67), and pre-existing cardiac disease (p = 0.04, HR 2.63, 95% CI 1.06 - 6.67) were associated with grade 3-5 cardiac toxicity. On MVA, both pre-existing cardiac disease (p < 0.01, HR 3.45, 95% CI 1.41 – 8.32), and use of NA CRT (p < 0.01, HR 3.45, 95% CI 1.35 - 9.09) predicted for grade 3-5 cardiac events. No dosimetric variable predicted for grade ≥3 cardiac events in the NA CRT group. Pericardial effusions (any grade) were significantly increased in the NA CRT group (26.4%) compared with surgery alone (7.1%) (p < 0.01, HR 1.75, 95% CI 1.06 - 2.94). This persisted on MVA (p < 0.01, HR 3.70, 95% CI 1.67 - 8.33). On UVA, the V35 Gy (p = 0.03), V45 Gy (p < 0.01), and V50 Gy (p = 0.04) were predictors of pericardial effusions. On MVA, the V45 Gy was the most significant independent predictor of pericardial effusions (p = 0.012, HR 1.03, 95% CI 1.01 - 1.06). A V45 Gy ≥ 33% cut off was the strongest dosimetric predictor of pericardial effusions (p < 0.001).

Conclusion: NA CRT followed by surgery significantly increased the rate of grade ≥3 cardiac events compared with patients treated with surgery alone. While no dosimetric parameter predicted for grade ≥3 cardiac events, the V45 Gy predicted for pericardial effusions. Keeping the V45 Gy to less than one third of the heart volume may reduce the incidence of pericardial effusions.

Author Disclosure: J.S. Witt: None. J.C. Jagodinsky: Student; University of Wisconsin School of Medicine and Public Health. Y. Liu: Graduate Student; University of Wisconsin Department of Statistics. P. Yadav: None. A. Kuczmarska-Haas: None. J.D. Maloney: None. M. Yu: None. M.A. Ritter: Research Grant; NCI. Vice Chair; University of Wisconsin Dept. of Human Oncology. A.M. Baschnagel: None.

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