PV QA 1 - Poster Viewing Q&A 1
SU_1_2009 - Overcoming the Barriers to the Use of Short Course Radiation Therapy in Locally Advanced Rectal Cancer: A Phase 1 Study of Short Course Radiation Therapy Concurrent with 5-Fluorouracil
Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3
Emma Fields, MD
Virginia Commonwealth University
Virginia Commonwealth University: Radiation Oncologist: Employee
Overcoming the Barriers to the Use of Short Course Radiation Therapy in Locally Advanced Rectal Cancer: A Phase 1 Study of Short Course Radiation Therapy Concurrent with 5-Fluorouracil
E. C. Fields1, B. Kaplan2, J. Karlin3, J. L. Myers1, N. D. Mukhopadhyay4, S. R. Grossman1, and K. Matin2; 1Virginia Commonwealth University, Richmond, VA, 2VCU Massey Cancer Center, Richmond, VA, 3Army, Kuala Lumpur, Malaysia, 4Virginia Commonwealth University Health System, Richmond, VA
Purpose/Objective(s): Short course (SC) RT is equivalent to long course (LC) RT for local control, disease free survival (DFS) and overall survival with similar rates of sphincter preservation and late toxicity in randomized studies. However, SC RT has not been adopted in the US for several reasons including: no opportunity for a synergistic effect of chemoRT, a delay to systemic therapy, less time for down-staging, and risk of increased late effects. This study aims to overcome these perceived barriers to the use of SC RT by determining a safe dose of continuous infusion (CI) 5-FU that may be combined with SC RT followed by 4 cycles of mFOLFOX, total mesorectal excision (TME) and 6 cycles of adjuvant mFOLFOX.
Materials/Methods: The primary objective was to determine the maximum tolerated dose (MTD) of CI 5-FU given concurrently with 5Gy x 5 fractions. Using the continual reassessment method, the dose of CI 5-FU was escalated from 100 to a MTD of 200mg/m2/day with 2 subjects per dose level and continued until 8 subjects were recruited to the MTD level. The secondary objectives included rate of clinical complete response (cCR) determined by imaging, pathologic complete response, rates of toxicity and 3 year local control and DFS (not yet reportable). Patients ≥ 18 years with cT3-4 or N+ rectal adenocarcinoma based on ultrasound or MRI were included. In an effort to mitigate the potential added toxicity from concurrent 5-FU, IMRT was used.
Results: 14 patients were enrolled from 2014-2017. All patients completed the study treatment of CI 5-FU and SC RT and the dose of 5-FU was safely escalated to 200mg/m2/day with no dose limiting toxicity. 93% completed the neoadjuvant mFOLFOX and only 1 patient went straight to surgery after chemoradiation. Clinical response was 22% complete, 64% partial, 14% stable disease and no patients had progression. Three patients with cCR had negative biopsies and did not have TME. Pathologic response was 21.4% complete, 64.3% partial, 14.3% stable disease and no one had pathologic progression. Grade 4 toxicity was reported in 1 patient (cytopenia), grade 3 in 8.6% and grade 1-2 in 91%. Most common toxicities were cytopenias, fatigue, diarrhea and nausea.
Conclusion: The preliminary results of this study show that SC RT can be safely and feasibly given with concurrent CI 5-FU and adds to the growing body of literature showing that SC RT is not only equivalent to LC RT, but may provide additional benefits in terms of allowing for a transition of full dose systemic therapy to the neoadjuvant setting, for selective organ preservation in complete responders, and providing a more convenient and cost-effective way of delivering pelvic radiotherapy.
Author Disclosure: E.C. Fields: None. B. Kaplan: None. J.L. Myers: None. N.D. Mukhopadhyay: None. S.R. Grossman: None. K. Matin: None.