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Published in: Annals of Surgical Oncology 11/2016

Open Access 01-10-2016 | Colorectal Cancer

Treatment Interval between Neoadjuvant Chemoradiotherapy and Surgery in Rectal Cancer Patients: A Population-Based Study

Authors: A. J. M. Rombouts, MD, N. Hugen, MD, PhD, M. A. G. Elferink, PhD, I. D. Nagtegaal, MD, PhD, J. H. W. de Wilt, MD, PhD

Published in: Annals of Surgical Oncology | Issue 11/2016

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Abstract

Background

Neoadjuvant chemoradiation therapy (CRT) has been widely implemented in the treatment of rectal cancer patients, but optimal timing of surgery after neoadjuvant therapy is unclear. The purpose of this study was to evaluate the effects of prolonged intervals between long-course CRT and surgery in rectal cancer patients.

Methods

Data on all rectal cancer patients diagnosed between 2006 and 2011 were retrieved from the population-based Netherlands Cancer Registry; the main outcome parameters were pathologic complete response (pCR) and overall survival (OS). Outcomes were reported separately for patients with early tumors (ETs; N = 217) and locally advanced rectal cancer (LARC; N = 1073). Patients were divided into 2-week interval groups according to treatment interval, ranging from 5–6 to 13–14 weeks. Kaplan–Meier curves, and logistic regression and Cox regression models were used for data analysis.

Results

No significant difference in pCR rate was observed for ET patients according to treatment interval. Compared with a treatment interval of 7–8 weeks, pCR rates in LARC patients were higher after 9–10 weeks (18.4 %; odds ratio [OR] 1.56, 95 % CI 1.03–2.37) and 11–12 weeks of treatment interval (20.8 %; OR 1.94, 95 % CI 1.15–3.26). Treatment interval did not influence OS in ET or LARC patients.

Conclusions

Treatment intervals of 9–12 weeks between surgery and CRT seem to improve the chances of pCR in LARC patients, without an effect on OS. The length of treatment interval did not affect outcomes in patients with ET. The ongoing search for minimally invasive surgery drives the need for exploration of factors that improve pathologic response.
Appendix
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Literature
1.
go back to reference van der Geest LG, Lam-Boer J, Koopman M, Verhoef C, Elferink MA, de Wilt JH. Nationwide trends in incidence, treatment and survival of colorectal cancer patients with synchronous metastases. Clin Exp Metastasis. 2015;32(5):457–65.CrossRefPubMed van der Geest LG, Lam-Boer J, Koopman M, Verhoef C, Elferink MA, de Wilt JH. Nationwide trends in incidence, treatment and survival of colorectal cancer patients with synchronous metastases. Clin Exp Metastasis. 2015;32(5):457–65.CrossRefPubMed
3.
go back to reference Gerard JP, Conroy T, Bonnetain F, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006;24(28):4620–25.CrossRefPubMed Gerard JP, Conroy T, Bonnetain F, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006;24(28):4620–25.CrossRefPubMed
4.
go back to reference Consensus statement on the multidisciplinary management of patients with recurrent and primary rectal cancer beyond total mesorectal excision planes. Br J Surg. 2013;100(8):E1-33. Consensus statement on the multidisciplinary management of patients with recurrent and primary rectal cancer beyond total mesorectal excision planes. Br J Surg. 2013;100(8):E1-33.
5.
go back to reference Denost Q, Adam JP, Rullier A, Buscail E, Laurent C, Rullier E. Perineal transanal approach: a new standard for laparoscopic sphincter-saving resection in low rectal cancer, a randomized trial. Ann Surg. 2014;260(6):993–9.CrossRefPubMed Denost Q, Adam JP, Rullier A, Buscail E, Laurent C, Rullier E. Perineal transanal approach: a new standard for laparoscopic sphincter-saving resection in low rectal cancer, a randomized trial. Ann Surg. 2014;260(6):993–9.CrossRefPubMed
6.
go back to reference Verseveld M, de Graaf EJ, Verhoef C, et al. Chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery (CARTS study). Br J Surg. 2015;102(7):853–60.CrossRefPubMed Verseveld M, de Graaf EJ, Verhoef C, et al. Chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery (CARTS study). Br J Surg. 2015;102(7):853–60.CrossRefPubMed
7.
go back to reference Morino M, Risio M, Bach S, et al. Early rectal cancer: the European Association for Endoscopic Surgery (EAES) clinical consensus conference. Surg Endosc. 2015;29(4):755–73.CrossRefPubMed Morino M, Risio M, Bach S, et al. Early rectal cancer: the European Association for Endoscopic Surgery (EAES) clinical consensus conference. Surg Endosc. 2015;29(4):755–73.CrossRefPubMed
8.
go back to reference Pucciarelli S, De Paoli A, Guerrieri M, et al. Local excision after preoperative chemoradiotherapy for rectal cancer: results of a multicenter phase II clinical trial. Dis Colon Rectum. 2013;56(12):1349–56.CrossRefPubMed Pucciarelli S, De Paoli A, Guerrieri M, et al. Local excision after preoperative chemoradiotherapy for rectal cancer: results of a multicenter phase II clinical trial. Dis Colon Rectum. 2013;56(12):1349–56.CrossRefPubMed
9.
go back to reference Garcia-Aguilar J, Shi Q, Thomas CR Jr, et al. A phase II trial of neoadjuvant chemoradiation and local excision for T2N0 rectal cancer: preliminary results of the ACOSOG Z6041 trial. Ann Surg Oncol. 2012;19(2):384–91.CrossRefPubMed Garcia-Aguilar J, Shi Q, Thomas CR Jr, et al. A phase II trial of neoadjuvant chemoradiation and local excision for T2N0 rectal cancer: preliminary results of the ACOSOG Z6041 trial. Ann Surg Oncol. 2012;19(2):384–91.CrossRefPubMed
10.
go back to reference Garcia-Aguilar J, Renfro LA, Chow OS, et al. Organ preservation for clinical T2N0 distal rectal cancer using neoadjuvant chemoradiotherapy and local excision (ACOSOG Z6041): results of an open-label, single-arm, multi-institutional, phase 2 trial. Lancet Oncol. 2015;16(15):1537–46.CrossRefPubMed Garcia-Aguilar J, Renfro LA, Chow OS, et al. Organ preservation for clinical T2N0 distal rectal cancer using neoadjuvant chemoradiotherapy and local excision (ACOSOG Z6041): results of an open-label, single-arm, multi-institutional, phase 2 trial. Lancet Oncol. 2015;16(15):1537–46.CrossRefPubMed
11.
go back to reference Stipa F, Picchio M, Burza A, Soricelli E, Vitelli CE. Long-term outcome of local excision after preoperative chemoradiation for ypT0 rectal cancer. Dis Colon Rectum. 2014;57(11):1245-1252.CrossRefPubMed Stipa F, Picchio M, Burza A, Soricelli E, Vitelli CE. Long-term outcome of local excision after preoperative chemoradiation for ypT0 rectal cancer. Dis Colon Rectum. 2014;57(11):1245-1252.CrossRefPubMed
12.
go back to reference Maas M, Beets-Tan RG, Lambregts DM, et al. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol. 2011;29(35):4633–40.CrossRefPubMed Maas M, Beets-Tan RG, Lambregts DM, et al. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol. 2011;29(35):4633–40.CrossRefPubMed
13.
go back to reference Habr-Gama A, Perez RO, Nadalin W, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004;240(4):711–7; discussion 717–8. Habr-Gama A, Perez RO, Nadalin W, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004;240(4):711–7; discussion 717–8.
14.
go back to reference Appelt AL, Ploen J, Harling H, et al. High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study. Lancet Oncol. 2015;16(8):919–27.CrossRefPubMed Appelt AL, Ploen J, Harling H, et al. High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study. Lancet Oncol. 2015;16(8):919–27.CrossRefPubMed
15.
go back to reference Calvo FA, Morillo V, Santos M, et al. Interval between neoadjuvant treatment and definitive surgery in locally advanced rectal cancer: impact on response and oncologic outcomes. J Cancer Res Clin Oncol. 2014;140(10):1651–60.CrossRefPubMed Calvo FA, Morillo V, Santos M, et al. Interval between neoadjuvant treatment and definitive surgery in locally advanced rectal cancer: impact on response and oncologic outcomes. J Cancer Res Clin Oncol. 2014;140(10):1651–60.CrossRefPubMed
17.
go back to reference Bokkerink GM, Buijs EF, de Ruijter W, et al. Improved quality of care for patients undergoing an abdominoperineal excision for rectal cancer. Eur J Surg Oncol. 2015;41(2):201–7.CrossRefPubMed Bokkerink GM, Buijs EF, de Ruijter W, et al. Improved quality of care for patients undergoing an abdominoperineal excision for rectal cancer. Eur J Surg Oncol. 2015;41(2):201–7.CrossRefPubMed
18.
go back to reference Petrelli F, Sgroi G, Sarti E, Barni S. Increasing the interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer: a meta-analysis of published studies. Ann Surg. 2013;00:1–8;263(3):458–64. Petrelli F, Sgroi G, Sarti E, Barni S. Increasing the interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer: a meta-analysis of published studies. Ann Surg. 2013;00:1–8;263(3):458–64.
19.
go back to reference Garcia-Aguilar J, Smith DD, Avila K, Bergsland EK, Chu P, Krieg RM. Optimal timing of surgery after chemoradiation for advanced rectal cancer: preliminary results of a multicenter, nonrandomized phase II prospective trial. Ann Surg. 2011;254(1):97–102.CrossRefPubMedPubMedCentral Garcia-Aguilar J, Smith DD, Avila K, Bergsland EK, Chu P, Krieg RM. Optimal timing of surgery after chemoradiation for advanced rectal cancer: preliminary results of a multicenter, nonrandomized phase II prospective trial. Ann Surg. 2011;254(1):97–102.CrossRefPubMedPubMedCentral
20.
go back to reference 20. Hugen N, Brown G, Glynne-Jones R, de Wilt JH, Nagtegaal ID. Advances in the care of patients with mucinous colorectal cancer. Nat Rev Clin Oncol. 2016;13(6):361–9.CrossRefPubMed 20. Hugen N, Brown G, Glynne-Jones R, de Wilt JH, Nagtegaal ID. Advances in the care of patients with mucinous colorectal cancer. Nat Rev Clin Oncol. 2016;13(6):361–9.CrossRefPubMed
21.
go back to reference Maas M, Nelemans PJ, Valentini V, et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010;11(9):835–44.CrossRefPubMed Maas M, Nelemans PJ, Valentini V, et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010;11(9):835–44.CrossRefPubMed
22.
go back to reference Sloothaak DA, Geijsen DE, van Leersum NJ, et al. Optimal time interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer. Br J Surg. 2013;100(7):933–39.CrossRefPubMed Sloothaak DA, Geijsen DE, van Leersum NJ, et al. Optimal time interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer. Br J Surg. 2013;100(7):933–39.CrossRefPubMed
23.
go back to reference Kalady MF, de Campos-Lobato LF, Stocchi L, et al. Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer. Ann Surg. 2009;250(4):582–9.PubMed Kalady MF, de Campos-Lobato LF, Stocchi L, et al. Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer. Ann Surg. 2009;250(4):582–9.PubMed
24.
go back to reference Petrelli F, Sgroi G, Sarti E, Barni S. Increasing the interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer: a meta-analysis of published studies. Ann Surg. 2016;263(3):458–64.CrossRefPubMed Petrelli F, Sgroi G, Sarti E, Barni S. Increasing the interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer: a meta-analysis of published studies. Ann Surg. 2016;263(3):458–64.CrossRefPubMed
25.
go back to reference de Campos-Lobato LF, Geisler DP, da Luz Moreira A, Stocchi L, Dietz D, Kalady MF. Neoadjuvant therapy for rectal cancer: the impact of longer interval between chemoradiation and surgery. J Gastrointest Surg. 2011;15(3):444–50. de Campos-Lobato LF, Geisler DP, da Luz Moreira A, Stocchi L, Dietz D, Kalady MF. Neoadjuvant therapy for rectal cancer: the impact of longer interval between chemoradiation and surgery. J Gastrointest Surg. 2011;15(3):444–50.
26.
go back to reference Al-Sukhni E, Attwood K, Mattson DM, Gabriel E, Nurkin SJ. Predictors of pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer. Ann Surg Oncol. 2016;23(4):1177–86.CrossRefPubMed Al-Sukhni E, Attwood K, Mattson DM, Gabriel E, Nurkin SJ. Predictors of pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer. Ann Surg Oncol. 2016;23(4):1177–86.CrossRefPubMed
27.
go back to reference Francois Y, Nemoz CJ, Baulieux J, et al. 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. 1999;17(8):2396.PubMed Francois Y, Nemoz CJ, Baulieux J, et al. 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. 1999;17(8):2396.PubMed
28.
go back to reference Saglam S, Bugra D, Saglam EK, et al. Fourth versus eighth week surgery after neoadjuvant radiochemotherapy in T3-4/N0 + rectal cancer: Istanbul R-01 study. J Gastrointest Oncol. 2014;5(1):9–17.PubMedPubMedCentral Saglam S, Bugra D, Saglam EK, et al. Fourth versus eighth week surgery after neoadjuvant radiochemotherapy in T3-4/N0 + rectal cancer: Istanbul R-01 study. J Gastrointest Oncol. 2014;5(1):9–17.PubMedPubMedCentral
29.
go back to reference Hugen N, van de Velde CJ, Bosch SL, et al. Modern treatment of rectal cancer closes the gap between common adenocarcinoma and mucinous carcinoma. Ann Surg Oncol. 2015;22(8):2669–76.CrossRefPubMed Hugen N, van de Velde CJ, Bosch SL, et al. Modern treatment of rectal cancer closes the gap between common adenocarcinoma and mucinous carcinoma. Ann Surg Oncol. 2015;22(8):2669–76.CrossRefPubMed
30.
go back to reference Borschitz T, Wachtlin D, Mohler M, Schmidberger H, Junginger T. Neoadjuvant chemoradiation and local excision for T2-3 rectal cancer. Ann Surg Oncol. 2008;15(3):712–20.CrossRefPubMed Borschitz T, Wachtlin D, Mohler M, Schmidberger H, Junginger T. Neoadjuvant chemoradiation and local excision for T2-3 rectal cancer. Ann Surg Oncol. 2008;15(3):712–20.CrossRefPubMed
31.
go back to reference Wolthuis AM, Penninckx F, Haustermans K, et al. Impact of interval between neoadjuvant chemoradiotherapy and TME for locally advanced rectal cancer on pathologic response and oncologic outcome. Ann Surg Oncol. 2012;19(9):2833–41.CrossRefPubMed Wolthuis AM, Penninckx F, Haustermans K, et al. Impact of interval between neoadjuvant chemoradiotherapy and TME for locally advanced rectal cancer on pathologic response and oncologic outcome. Ann Surg Oncol. 2012;19(9):2833–41.CrossRefPubMed
32.
go back to reference Tulchinsky H, Shmueli E, Figer A, Klausner JM, Rabau M. 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. 2008;15(10):2661–7.CrossRefPubMed Tulchinsky H, Shmueli E, Figer A, Klausner JM, Rabau M. 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. 2008;15(10):2661–7.CrossRefPubMed
33.
go back to reference Lim SB, Choi HS, Jeong SY, et al. Optimal surgery time after preoperative chemoradiotherapy for locally advanced rectal cancers. Ann Surg. 2008;248(2):243–51.CrossRefPubMed Lim SB, Choi HS, Jeong SY, et al. Optimal surgery time after preoperative chemoradiotherapy for locally advanced rectal cancers. Ann Surg. 2008;248(2):243–51.CrossRefPubMed
36.
go back to reference Lefevre JH, Rousseau A, Svrcek M, et al. A multicentric randomized controlled trial on the impact of lengthening the interval between neoadjuvant radiochemotherapy and surgery on complete pathological response in rectal cancer (GRECCAR-6 trial): rationale and design. BMC Cancer 2013;13:417.CrossRefPubMedPubMedCentral Lefevre JH, Rousseau A, Svrcek M, et al. A multicentric randomized controlled trial on the impact of lengthening the interval between neoadjuvant radiochemotherapy and surgery on complete pathological response in rectal cancer (GRECCAR-6 trial): rationale and design. BMC Cancer 2013;13:417.CrossRefPubMedPubMedCentral
Metadata
Title
Treatment Interval between Neoadjuvant Chemoradiotherapy and Surgery in Rectal Cancer Patients: A Population-Based Study
Authors
A. J. M. Rombouts, MD
N. Hugen, MD, PhD
M. A. G. Elferink, PhD
I. D. Nagtegaal, MD, PhD
J. H. W. de Wilt, MD, PhD
Publication date
01-10-2016
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 11/2016
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5294-0

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