The Impact of Surgical Timing on Pathologic Tumor Response after Short Course and Long Course Preoperative Chemoradiation for Locally Advanced Rectal Adenocarcinoma
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Purpose A pooled analysis of multi-institutional trials was performed to analyze the effect of surgical timing on tumor response by comparing short course concurrent chemoradiotherapy (CCRT) with long course CCRT followed by delayed surgery in locally advanced rectal cancer. Materials and Methods Three hundred patients with cT3-4N0-2 rectal adenocarcinoma were included. Long course patients from KROG 14-12 (n=150) were matched 1:1 to 150 short course patients from KROG 10-01 (NCT01129700) and KROG 11-02 (NCT01431599) according to stage, age, and other risk factors. The primary endpoint was to determine the interval between surgery and the last day of neoadjuvant CCRT which yields the best tumor response after the short course and long course CCRT. Downstaging was defined as ypT0-2N0M0 and pathologic complete response (ypCR) was defined as ypT0N0M0, respectively. Results Both the long and short course groups achieved lowest downstaging rates at < 6 weeks (long 20% vs. short 8%) and highest downstaging rates at 6-7 weeks (long 44% vs. short 40%). The ypCR rates were lowest at < 6 weeks (both long and short 0%) and highest at 6-7 weeks (long 21% vs. short 11%) in both the short and long course arms. The downstaging and ypCR rates of long course group gradually declined after the peak at 6-7 weeks and those of the short course group trend to constantly increase afterwards. Conclusion It is optimal to perform surgery at least 6 weeks after both the short course and long course CCRT to obtain maximal tumor regression in locally advanced rectal adenocarcinoma.
Abstract
Purpose A pooled analysis of multi-institutional trials was performed to analyze the effect of surgical timing on tumor response by comparing short course concurrent chemoradiotherapy (CCRT) with long course CCRT followed by delayed surgery in locally advanced rectal cancer. Materials and Methods Three hundred patients with cT3-4N0-2 rectal adenocarcinoma were included. Long course patients from KROG 14-12 (n=150) were matched 1:1 to 150 short course patients from KROG 10-01 (NCT01129700) and KROG 11-02 (NCT01431599) according to stage, age, and other risk factors. The primary endpoint was to determine the interval between surgery and the last day of neoadjuvant CCRT which yields the best tumor response after the short course and long course CCRT. Downstaging was defined as ypT0-2N0M0 and pathologic complete response (ypCR) was defined as ypT0N0M0, respectively. Results Both the long and short course groups achieved lowest downstaging rates at < 6 weeks (long 20% vs. short 8%) and highest downstaging rates at 6-7 weeks (long 44% vs. short 40%). The ypCR rates were lowest at < 6 weeks (both long and short 0%) and highest at 6-7 weeks (long 21% vs. short 11%) in both the short and long course arms. The downstaging and ypCR rates of long course group gradually declined after the peak at 6-7 weeks and those of the short course group trend to constantly increase afterwards. Conclusion It is optimal to perform surgery at least 6 weeks after both the short course and long course CCRT to obtain maximal tumor regression in locally advanced rectal adenocarcinoma.
참고문헌 (33)
- 오창모, "Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2013", Cancer Research and Treatment, 48(2), pp.436~450 (2016), 대한암학회
- 이홍석, "Correlation between tumor regression grade and rectal volume in neoadjuvant concurrent chemoradiotherapy for rectal cancer", Radiation oncology journal, 34(3), pp.186~192 (2016), 대한방사선종양학회
- Yeo SG, "Preoperative short-course concurrent chemoradiation therapy followed by delayed surgery for locally advanced rectal cancer: a phase 2 multicenter study (KROG 10-01)", Int J Radiat Oncol Biol Phys, 86, pp.34~39 (2013)[DOI]
- Lee JH, "Two-week course of preoperative chemoradiotherapy followed by delayed surgery for rectal cancer: a phase II multiinstitutional clinical trial (KROG 11-02)", Radiother Oncol, 110, pp.150~154 (2014)[DOI]
- Stein DE, "Longer time interval between completion of neoadjuvant chemoradiation and surgical resection does not improve downstaging of rectal carcinoma", Dis Colon Rectum, 46, pp.448~453 (2003)[DOI]
- Tulchinsky H, "An interval > 7 weeks between neoadjuvant therapy and surgery improves pathologic complete response and disease-free survival in patients with locally advanced rectal cancer", Ann Surg Oncol, 15, pp.2661~2667 (2008)[DOI]
- Habr-Gama A, "Interval between surgery and neoadjuvant chemoradiation therapy for distal rectal cancer: does delayed surgery have an impact on outcome?", Int J Radiat Oncol Biol Phys, 71, pp.1181~1188 (2008)[DOI]
- Coucke PA, "Effect of timing of surgery on survival after preoperative hyperfractionated accelerated radiotherapy (HART) for locally advanced rectal cancer (LARC): is it a matter of days?", Acta Oncol, 45, pp.1086~1093 (2006)[DOI]
- Lefevre JH, "Effect of interval (7 or 11 weeks) between neoadjuvant radiochemotherapy and surgery on complete pathologic response in rectal cancer: a multicenter, randomized, controlled trial (GRECCAR-6)", J Clin Oncol, 34, pp.3773~3780 (2016)[DOI]
- Lim SB, "Optimal surgery time after preoperative chemoradiotherapy for locally advanced rectal cancers", Ann Surg, 248, pp.243~251 (2008)[DOI]
- van den Broek CB, "Impact of the interval between short-course radiotherapy and surgery on outcomes of rectal cancer patients", Eur J Cancer, 49, pp.3131~3139 (2013)[DOI]
- Hatfield P, "Short-course radiotherapy, with elective delay prior to surgery, in patients with unresectable rectal cancer who have poor performance status or significant co-morbidity", Radiother Oncol, 92, pp.210~214 (2009)[DOI]
- Francois Y, "Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial", J Clin Oncol, 17, pp.2396~ (1999)[DOI]
- Lee JH, "Carcinoembryonic antigen has prognostic value for tumor downstaging and recurrence in rectal cancer after preoperative chemoradiotherapy and curative surgery: a multi-institutional and case-matched control study of KROG 14-12", Radiother Oncol, 116, pp.202~208 (2015)[DOI]
- Heald RJ, "The mesorectum in rectal cancer surgery: the clue to pelvic recurrence?", Br J Surg, 69, pp.613~616 (1982)[DOI]
- Folkesson J, "Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate", J Clin Oncol, 23, pp.5644~5650 (2005)[DOI]
- Sauer R, "Preoperative versus postoperative chemoradiotherapy for rectal cancer", N Engl J Med, 351, pp.1731~1740 (2004)[DOI]
- Bujko K, "Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer", Br J Surg, 93, pp.1215~1223 (2006)[DOI]
- Fang CB, "Is the delayed surgery after neoadjuvant chemoradiation beneficial for locally advanced rectal cancer?", Arq Bras Cir Dig, 26, pp.31~35 (2013)[DOI]
- de Campos-Lobato LF, "Neoadjuvant therapy for rectal cancer: the impact of longer interval between chemoradiation and surgery", J Gastrointest Surg, 15, pp.444~450 (2011)[DOI]
- Chung MJ, "Preoperative short- vs. long-course chemoradiotherapy with delayed surgery for locally advanced rectal cancer", Oncotarget, 8, pp.60479~60486 (2017)
- Kim JJ, "Repopulation of cancer cells during therapy: an important cause of treatment failure", Nat Rev Cancer, 5, pp.516~525 (2005)[DOI]
- Dhadda AS, "Regression of rectal cancer with radiotherapy with or without concurrent capecitabine: optimising the timing of surgical resection", Clin Oncol (R Coll Radiol), 21, pp.23~31 (2009)[DOI]
- Sloothaak DA, "Optimal time interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer", Br J Surg, 100, pp.933~939 (2013)[DOI]
- Wasserberg N, "Interval to surgery after neoadjuvant treatment for colorectal cancer", World J Gastroenterol, 20, pp.4256~4262 (2014)[DOI]
- Barton MB, "The effect of treat-ment time and treatment interruption on tumour control following radical radiotherapy of laryngeal cancer", Radiother Oncol, 23, pp.137~143 (1992)[DOI]
- Begg AC, "Tumour cell repopulation during fractionated radiotherapy: correlation between flow cytometric and radiobiological data in three murine tumours", Eur J Cancer, 27, pp.537~543 (1991)[DOI]
- Gasinska A, "Gender-related differences in repopulation and early tumor response to preoperative radiotherapy in rectal cancer patients", J Gastrointest Surg, 15, pp.1568~1576 (2011)[DOI]
- Peters LJ, "Applying radiobiological principles to combined modality treatment of head and neck cancer: the time factor", Int J Radiat Oncol Biol Phys, 39, pp.831~836 (1997)[DOI]
- Kwak YK, "Timely tumor response analysis after preoperative chemoradiotherapy and curative surgery in locally advanced rectal cancer: a multi-institutional study for optimal surgical timing in rectal cancer", Radiother Oncol, 119, pp.512~518 (2016)[DOI]
- Trott KR, "Rapid repopulation in radiotherapy: a debate on mechanism. Accelerated repopulation in tumours and normal tissues", Radiother Oncol, 22, pp.159~160 (1991)[DOI]
- Evans J, "Results of a prospective randomised control 6 vs 12 trial: is greater tumour downstaging observed on post treatment MRI if surgery is delayed to 12-weeks versus 6-weeks after completion of neoadjuvant chemoradiotherapy", Ann Oncol, 27(Suppl 6), pp.vi149~ (2016)[DOI]
- Rose BS, "Perils of the pathologic complete response", J Clin Oncol, 34, pp.3959~3962 (2016)[DOI]
