Outcomes of the non-surgical management of locally advanced rectal cancer after neoadjuvant treatment
Keywords:
Rectal cancer, Neoadjuvant therapy, Complete clinical response, Non-surgical management, Tumor markersAbstract
Objectives: To describe the clinical and histopathological characteristics and outcomes of patient with non-surgically managed locally advanced rectal cancer and a complete clinical response to neoadjuvant treatment.
Methods: A retrospective study was conducted on a cohort of patients with stages II and III rectal cancer, on clinical follow up after subjected to chemoradiotherapy. The overall disease free survival and recurrence rates were evaluated. The biological (Kras, Ki67, p53) and morphological (grade, lymphovascular and perineural invasion) characteristics of the tumor were recorded.
Results: Between January 2003 and June 2013, a total of 19 patients with locally advanced rectal cancer and a complete clinical response after neoadjuvant treatment, did not accept radical surgical treatment. With a median follow-up of 21 months (range 4-92 months), the recurrences were: 21% in the first year, 36% at 3 years, and 42% at 5 years (total: 8 patients). There was local recurrence in 50% of the cases, regional in 50%, and there were no systemic recurrences. The estimated local recurrence rate was 2.3 recurrences per 100 patients/month
(95% CI; 1.21 --- 4.5), and a regional recurrence of 1.3 recurrences per 100 patients/month (95% CI: 0.5 --- 3.1). No relationship was found between the expression of biological factors of the primary tumor and the outcomes.
Conclusions: The indication for radical surgical treatment after neoadjuvant treatment is demonstrated in all patients with locally advanced rectal cancer. The low local and regional recurrence rates of this series suggest the possibility of local resection or observation in selected cases. Individualization and the wishes of the patient must be taken into account when making decisions.
Author Biographies
Pilar Adriana Torres Mesa, Instituto Nacional de Cancerología
Grupo de Cirugía Gastrointestinal Oncológica y Endoscopia Digestiva, Instituto Nacional de Cancerología, Bogotá D.C., Colombia
Ricardo Oliveros, Instituto Nacional de Cancerología
Grupo de Cirugía Gastrointestinal Oncológica y Endoscopia Digestiva, Instituto Nacional de Cancerología, Bogotá D.C., Colombia
Jorge Mesa, Instituto Nacional de Cancerología
Grupo de Patología Oncológica, Instituto Nacional de Cancerología, Bogotá D.C., Colombia
Natalia Olaya, Instituto Nacional de Cancerología
Grupo de Patología Oncológica, Instituto Nacional de Cancerología, Bogotá D.C., Colombia
Ricardo Sánchez, Instituto Nacional de Cancerología
Grupo de Investigación Clínica, Instituto Nacional de Cancerología, Bogotá, D.C, Colombia
References
Siegel R, Naishadham D, Jemal A. Cancer statistics. Ca Cancer J Clin. 2013;63:11-30.
https://doi.org/10.3322/caac.21166
van de Velde CJ, Boelens PG, Borras JM, Coebergh JW, Cervantes A, Blomqvist L, et al. EURECCA colorectal: Multidisciplinary management: European consensus conference Colon & Rectum. Eur J Cancer. 2014;50, e1-e1.e34.
https://doi.org/10.1016/j.ejca.2013.06.048
Instituto Nacional de Cancerología. Anuarios estadísticos 2003- 2011.
Piñeros M, Pardo C, Gamboa O, Hernández G. Atlas de mortalidad por cáncer en Colombia, tercera edición. Bogotá: Instituto Nacional de Cancerología; Instituto Geográfico Agustín Codazzi; 2010.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology, Rectal Cancer, Version 2.2014. URL: http://www.nccn.org/professionals/physiciangls/fguidelines.asp.
Meredith KL, Hoffe SE, Shibata D. The multidisciplinary management of rectal cancer. Surg Clin N Am. 2009;89:177-215.
https://doi.org/10.1016/j.suc.2008.09.021
Akasu T, Linuma G, Takawa M, Yamamoto S, Muramatsu Y, Moriyama N. Accuracy of high-resolution magnetic resonance imaging in preoperative staging of rectal cancer. Ann Surg Oncology. 2009;16:2787-94.
https://doi.org/10.1245/s10434-009-0613-3
CaiG,XuY,ZhuJ,GuWL,ZhangS,MaXJ,etal. Diffusion-weightedmagnetic resonance imaging for predicting the response of rectal cancer to neoadjuvant concurrent chemoradiation. World J Gastroenterol. 2013;19:5520-7.
https://doi.org/10.3748/wjg.v19.i33.5520
Halefoglu AM, Yildirim S, Avlanmis O, Sakiz D, Baykan A. Endorectal ultrasonography versus phased array magnetic resonance imaging for preoperative staging of rectal cancer. World Journal Gastroenterology. 2008;14:3504-10.
https://doi.org/10.3748/wjg.14.3504
Bayraktar Y, Kav T. How useful is rectal endosonography in the staging of rectal cancer? World Journal of Gastroenterology. 2010;16(6):691-7.
https://doi.org/10.3748/wjg.v16.i6.691
Chan K, Welch S, Walker-Dilks C, Raifu A. Evidence-based guideline recommendations on the use of Positron Emission Tomography imaging in Colorectal cancer. Clinical Oncology. 2012;24:232-49.
https://doi.org/10.1016/j.clon.2011.11.008
Glynne-Jones R, Kronfli M. Locally advanced rectal cancer: A comparison of management strategies. Drugs. 2011;71(9): 1153-77.
https://doi.org/10.2165/11591330-000000000-00000
Valentini V, Beets-Tan R, Borras JM, KrivokapicZ ́, Leer JW, Pahlman L, et al. Evidence and research in rectal cancer. Radiotherapy and Oncology. 2008;87:449-74.
https://doi.org/10.1016/j.radonc.2008.05.022
McCarthy K, Pearson K, Fulton R, Hewitt J. Pre-operative chemoradiation for non-metastatic locally advanced rectal cancer. Cochrane Database of Systematic Reviews. 2012;(12). Art. No: CD008368. DOI: 10.1002/14651858.CD008368.
https://doi.org/10.1002/14651858.CD008368
Ceelen WP, Nieuwenhove YV, Fierens K. Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer. Cochrane Database Syst Rev. 2009;(1). Art No: CD006041DOI:101012/14651858CD006041pub2.
https://doi.org/10.1002/14651858.CD006041.pub2
Conde S, Borrego M, Teixeira T, Teixeira R, Sáb A, Soarez A. Neoadjuvant oral vs. infusional chemoradiotherapy on locally advanced rectal cancer: Prognostic factors. Rep Pract Oncol Radiother. 2013;18(2):67-75.
https://doi.org/10.1016/j.rpor.2012.07.010
Lee SU, Kim DY, Kim SY, Baek JY, Chang HJ, Kim MJ, et al. Comparison of two preoperative chemoradiotherapy regimens for locally advanced Rectal cancer: Capecitabine alone versus capecitabine plus irinotecan. Radiation Oncology. 2013;8: 258.
https://doi.org/10.1186/1748-717X-8-258
Viani GA, Stefano EJ, Soares FV, Afonso SL. Evaluation of biologic effective dose and schedule of fractionation for preoperative radiotherapy for rectal cancer: Meta-analyses and metaregression. Int J Radiation Oncology Biol Phys. 2011;80:985-91.
https://doi.org/10.1016/j.ijrobp.2010.03.008
Habr-Gama A, Perez RO, Nadalin W, Nahas SC, Ribeiro Jr U, Silva e Sousa EH. Long-term results of preoperative chemoradiation for distal rectal cancer correlation between final stage and survival. J Gastrointest Surg. 2005;9:90-101.
https://doi.org/10.1016/j.gassur.2004.10.010
Rullier E, Denost Q, Vendrely V, Rullier A, Laurent C. Low Rectal Cancer: Classification and Standardization of Surgery. Dis Colon Rectum. 2013;56:560-7.
https://doi.org/10.1097/DCR.0b013e31827c4a8c
Evans J, Tait D, Swift I, Pennert K, Tekkis P, Wotherspoon A, et al. Timing of Surgery Following Preoperative Therapy in Rectal Cancer: The Need for a Prospective Randomized Trial? Dis Colon Rectum. 2011;54:1251-9.
https://doi.org/10.1097/DCR.0b013e3182281f4b
Weisser M, Beets-Tan R, Beets G. Management of complete response after chemoradiation in rectal cancer. Surg Oncol Clin N Am. 2014;23:113-25.
https://doi.org/10.1016/j.soc.2013.09.012
Habr-Gama A, Perez RO, Wynn G, Marks J, Kessler H, Gama Rodrigues J. Complete clinical response after neoadjuvant chemoradiation therapy for distal rectal cancer: Characterization of clinical and endoscopic findings for standardization. Dis Colon Rectum. 2010;53:1692-8.
https://doi.org/10.1007/DCR.0b013e3181f42b89
Habr-Gama A, Perez R, Proscurshim I, Gama-Rodrigues J. Complete clinical response after neoadjuvant chemoradiation for distal rectal cancer. Surg Oncol Clin N Am. 2010;19:829-45.
https://doi.org/10.1016/j.soc.2010.08.001
Mignanelli ED, Campos-Lobato LF, Stocchi L, Lavery IC, Dietz DW. Downstaging after chemoradiotherapy for locally advanced rectal cancer: Is there more (tumor) than meets the eye? Diseases of the Colon & Rectum. 2010; 53.(3).
https://doi.org/10.1007/DCR.0b013e3181bcd3cc
Thies S, Langer R. Tumor regression grading of gastrointestinal carcinomas after neoadjuvant treatment. Front Oncol. 2013;3:262,
https://doi.org/10.3389/fonc.2013.00262
Franklin JM, Anderson EM, Gleeson FV. MRI features of the complete histopathological response of locally advanced rectal cancer to neoadjuvant chemoradiotherapy. Clinical Radiology. 2012;67:546-52.
https://doi.org/10.1016/j.crad.2011.11.004
Mak D, Joon DL, Chao M, Wada M, Joon ML, See A. The use of PET in assessing tumor response after neoadjuvant chemoradiation for rectal cancer. Radiotherapy and Oncology. 2010;97:205-11.
https://doi.org/10.1016/j.radonc.2010.05.016
Hongyoon C, Hai-jeon Y, Tae Sung K, Jae Hwan O, Dae Yong K, Seok-ki K. Voxel-based dual-time 18F-FDG parametric imaging for rectal cancer: differentiation of residual tumor from postchemoradiotherapy changes. Nuclear Medicine Communications. 2013;34:1166-73.
Figueiras RG, Domínguez PC, García Dorrego R, Vázquez Martín A, Caaman ̃o AG. Prognostic factors and functional imaging in rectal cancer. Radiología. 2012;54:45-58.
https://doi.org/10.1016/j.rxeng.2012.05.004
Dalton RS, Velineni R, Osborne ME, Thomas R, Harries S, Gee AS, Daniels IS. A single centre experience of chemoradiotherapy for rectal cancer: is there potential for nonoperative management? Colorectal Disease. 2011;14:567-71.
https://doi.org/10.1111/j.1463-1318.2011.02752.x
O'Neill BD, Brown G, Heald RJ. Non-operative treatment after neoadjuvant chemoradiotherapy for rectal cancer. Lancet Oncol. 2007;8:625-33.
https://doi.org/10.1016/S1470-2045(07)70202-4
Fischkoff KN, Ruby JA, Guillem JG. Nonoperative approach to locally advanced rectal cancer after neoadjuvant combined modality therapy: challenges and opportunities from a surgical perspective. Clinical Colorectal Cancer. 2011;10:291-7.
https://doi.org/10.1016/j.clcc.2011.06.001
Higgins KA, Willett CG, Czito BG. Nonoperative management of rectal cancer: Current perspectives. Clinical Colorectal Cancer. 2010;9:83-8.
https://doi.org/10.3816/CCC.2010.n.011
Habr-Gama A, de Souza PM, Ribeiro Jr U, Nadalin W, Gansl R, Sousa Jr AH, et al. Low rectal cancer: Impact of radiation and chemotherapy on surgical treatment. Dis Colon Rectum. 1998;41:1087-96.
https://doi.org/10.1007/BF02239429
Habr-Gama A, Perez RO, São Julião GP, Proscurshim I, Gama- Rodrigues J. Nonoperative approaches to rectal cancer: A critical evaluation. Semin Radiat Oncol. 2011;21:234-9.
https://doi.org/10.1016/j.semradonc.2011.02.010
Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro Jr U, Silva e Sousa Jr AH, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: Long-term Results. Ann Surg. 2004;240:711-8.
https://doi.org/10.1097/01.sla.0000141194.27992.32
Habr-Gama A, Perez RO, Proscurshim I, Campos FG, Nadalin W, Kiss D, et al. Patterns of failure and survival for nonoperative treatment of stage c0 distal rectal cancer following neoadjuvant chemoradiation therapy. J Gastrointest Surg. 2006;10:1319-29.
https://doi.org/10.1016/j.gassur.2006.09.005
Perez RO, São Julião GP, Habr-Gama A, Kiss D, Proscurshim I, Campos FG, et al. The role of carcinoembriogenic antigen in predicting response and survival to neoadjuvant chemoradiotherapy for distal rectal cancer. Dis Colon Rectum. 2009;52:1137-43.
https://doi.org/10.1007/DCR.0b013e31819ef76b
Chung MJ, Chung SM, Kim JY, Ryu MR. Prognostic significance of serum carcinoembryonic antigen normalization on survival in rectal cancer treated with preoperative chemoradiation. Cancer Res Treat. 2013;45:186-92.
https://doi.org/10.4143/crt.2013.45.3.186
Liebig C, Ayala G, Wilks J, Verstovsek G, Liu H, Agarwal N, et al. Perineural invasion is an independent predictor of outcome in colorectal cancer. J Clin Oncol. 2009;27:5131-7.
https://doi.org/10.1200/JCO.2009.22.4949
Díez M, Perez J, Martín A. Marcadores tumorales de valor pronóstico en adenocarcinomas de colon y recto. Gastroenterología integrada. 2001;2(4):207-21.
Garcia-Aguilar J, Chen Z, Smith DD, Li W, Madoff RD, Cataldo P, et al. Identification of a biomarker profile associated with resistance to neoadjuvant chemoradiation therapy in rectal cancer. Ann Surg. 2011;254:486-93.
https://doi.org/10.1097/SLA.0b013e31822b8cfa
Chen Z, Duldulao MP, Li W, Lee W, Kim J, Garcia-Aguilar J. Molecular diagnosis of response to neoadjuvant chemoradiation therapy in patients with locally advanced rectal cancer. J Am Coll Surg. 2011;212:1008-17.
https://doi.org/10.1016/j.jamcollsurg.2011.02.024
Lopez-Crapez E, Bibeau F, Thézenas S, Ychou M, SimonyLafontaine J, Thirion A, et al. p53 status and response to radiotherapy in rectal cancer: a prospective multilevel analysis. Br J Cancer. 2005;92:2114-21.
https://doi.org/10.1038/sj.bjc.6602622
Lin LC, Lee HH, Hwang WS, Li CF, Huang CT, Que J, et al. p53 and p27 as predictors of clinical outcome for rectal-cancer patients receiving neoadjuvant therapy. Surg Oncol. 2006;15:211-6.
https://doi.org/10.1016/j.suronc.2007.01.001
Kuremsky JG, Tepper JE, McLeod HL. Biomarkers for response to neoadjuvant chemoradiation for rectal cancer. Int J Radiat Oncol Biol Phys. 2009;74:673-88.
https://doi.org/10.1016/j.ijrobp.2009.03.003
Kato S, Iida S, Higuchi T, Ishikawa T, Takagi Y, Yasuno M, et al. PIK3CA mutation is predictive of poor survival in patients with colorectal cancer. Int J Cancer. 2007;121:1771-8.
https://doi.org/10.1002/ijc.22890
Nosho K, Kawasaki T, Ohnishi M, Suemoto Y, Kirkner GJ, Zepf D, et al. PIK3CA mutation in colorectal cancer: Relationship with genetic and epigenetic alterations. Neoplasia. 2008;10:534-41.
https://doi.org/10.1593/neo.08336
Imamura Y, Morikawa T, Liao X, Lochhead P, Kuchiba A, Yamauchi M, et al. Specific Mutations in KRAS Codons 12 and 13, and Patient Prognosis in 1075 BRAF Wild-Type Colorectal Cancers. Clin Cancer Res. 2012;18:4753-63.
https://doi.org/10.1158/1078-0432.CCR-11-3210
Bengala C, Bettelli S, Bertolini F, Salvi S, Chiara S, Sonaglio C, et al. Epidermal growth factor receptor gene copy number. K-ras mutation and pathological response to preoperative cetuximab, 5-FU and radiation therapy in locally advanced rectal cancer Ann Oncol. 2009;20:469-74.
https://doi.org/10.1093/annonc/mdn647
Zeestraten EC, Kuppen PJ, van de Velde CJ, Marijnen CA. Prediction in rectal cancer. Semin Radiat Oncol. 2012;22:175-83.
https://doi.org/10.1016/j.semradonc.2011.12.005
Moureau-Zabotto L, Farnault B, de Chaisemartin C, Esterni B, Lelong B, Viret F, et al. Predictive factors of tumor response after neoadjuvant chemoradiation for locally advanced rectal cancer. Int J Radiation Oncology Biol Phys. 2011;80:483-91.
https://doi.org/10.1016/j.ijrobp.2010.02.025
Guedj N, Bretagnol F, Rautou PE. Predictors of tumor response after preoperative chemoradiotherapy for rectal adenocarcinomas. Human Pathology. 2011;42:1702-9.
https://doi.org/10.1016/j.humpath.2011.01.015
Pucciarelli S, De Paoli A, Guerrieri M, La Torre G, Maretto I, De Marchi F, et al. Local excision after preoperative chemoradiotherapy for rectal cancer: results of a multicenter phase II clinical trial. Dis Colon Rectum. 2013;56:1349-56.
https://doi.org/10.1097/DCR.0b013e3182a2303e
Kundel Y, Brenner R, Purim O, Peled N, Idelevich E, Fenig E, et al. Is local excision after complete pathological response to neoadjuvant chemoradiation for rectal cancer an acceptable treatment option? Dis Colon Rectum. 2010;53:1624-31.
https://doi.org/10.1007/DCR.0b013e3181f5b64d
Bujko K, Sopyloy R, Kepka L. Local excision after radio (chemo) therapy for rectal cancer: is it safe? Clinical Oncology. 2007;19:693-700.
https://doi.org/10.1016/j.clon.2007.07.014
Perez RO, Habr-Gama A, Lynn PB, São Julião GP, Bianchi R, Proscurshim I, et al. Transanal endoscopic microsurgery for residual rectal cancer (ypT0-2) following neoadjuvant chemoradiation therapy: another Word of Caution. Dis Colon Rectum. 2013;56:6-13.
https://doi.org/10.1097/DCR.0b013e318273f56f
Colombo PE, Patani N, Bibeau F, Assenat E, Bertrand MM, Senesse P, et al. Clinical impact of lymph node status in rectal cancer. Surgical Oncology. 2011;20:227-33.
https://doi.org/10.1016/j.suronc.2011.08.004
Habr-Gama A, Perez RO, Sabbaga J, Nadalin W, São Julião GP, Gama-Rodrigues J. Increasing the rates of complete response to neoadyuvant chemoradiotherapy for distal rectal cancer: results of a prospective study using additional chemotherapy during the resting period. Dis Colon Rectum. 2009;52(12):1927-34.
https://doi.org/10.1007/DCR.0b013e3181ba14ed
Lim L, Chao M, Shapiro J, Millar JL, Kipp D, Rezo A, et al. Long-term outcomes of patients with localized rectal cancer treated with chemoradiation or radiotherapy alone because of medical inoperability or patient refusal. Dis Colon Rectum. 2007;50(12):2032-9.
https://doi.org/10.1007/s10350-007-9062-x
Glynne-Jones R, Wallace M, Livingstone JI, Meyrick-Thomas J. Complete clinical response after preoperative chemoradiation in rectal cancer: Is a ''wait and see'' policy justified? Dis Colon Rectum. 2008;51:10-20.
https://doi.org/10.1007/s10350-007-9080-8
Hughes R, Harrison M, Glynne-Jones R. Could a wait and see policy be justified in T3/4 rectal cancers after chemoradiotherapy? Acta Oncológica. 2010;49:378-81.
https://doi.org/10.3109/02841860903483692
Neuman HB, Elkin EB, Guillem JG, Paty PB, Weiser MR, Wong WD, et al. Treatment for patients with rectal cancer and a clinical complete response to neoadjuvant therapy: a decision analysis. Dis Colon Rectum. 2009;52(5):863-71.
https://doi.org/10.1007/DCR.0b013e31819eefba
Jacobson O, Chen X. Interrogating tumor metabolism and tumor microenvironments using molecular positron emission tomography imaging. Theranostic approaches to improve therapeutics Pharmacol Rev. 2013;65:1214-56.
https://doi.org/10.1124/pr.113.007625
Lambregts DM, Maas M, Bakers FC, Cappendijk VC, Lammering G, Beets GL, et al. Longterm follow-up features on rectal MRI during a wait-and-see approach after a clinical complete response in patients with rectal cancer treated with chemoradiotherapy. Dis Colon Rectum. 2011;54:1521-8.
https://doi.org/10.1097/DCR.0b013e318232da89
Haustermans K, Debucquoy A, Lambrecht M, The ESTRO. Breur Lecture 2010: Towards a tailored patient approach in rectal cancer. Radiotherapy and Oncology. 2011;100:15-21.
https://doi.org/10.1016/j.radonc.2011.05.024
Smith FM, Waldron D, Winter DC. Rectum-conserving surgery in the era of chemoradiotherapy. Br J Surg. 2010;97: 1752-64.
https://doi.org/10.1002/bjs.7251
Perez RO, Pereira DD, Proscurshim I, Gama-Rodrigues J, Rawet V, São Julião GP, et al. Lymph node size in rectal cancer following neoadjuvant chemoradiation-Can we rely on radiologic nodal staging after chemoradiation? Dis Colon Rectum. 2009;52:1278-84.
https://doi.org/10.1007/DCR.0b013e3181a0af4b
Martin ST, Heneghan MH, Winter DC. Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer. British Journal of Surgery. 2012;99:918-28.
https://doi.org/10.1002/bjs.8702
Maas M, Nelemans PJ, Valentini V, Das P, Rödel C, Kuo LJ, 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;11:835-44.
https://doi.org/10.1016/S1470-2045(10)70172-8
Perez RO, Habr-Gama A, Pereira GV, Lynn PB, Alves PA, Proscurshim I, et al. Role of biopsies in patients with residual rectal cancer following neoadjuvant chemoradiation after downsizing: can they rule out persisting cancer? Colorectal Disease. 2011;14:714-20.
https://doi.org/10.1111/j.1463-1318.2011.02761.x
Smith FM, Chang KH, Sheahan K, Hyland J, O'Connell PR, Winter DC. The surgical significance of residual mucosal abnormalities in rectal cancer following neoadjuvant chemoradiotherapy. British Journal of Surgery. 2012;99:993-1001.
https://doi.org/10.1002/bjs.8700
Hayden DM, Jakate S, Pinzon MC, Giusto D, Francescatti AB, Brand MI, et al. Tumor scatter after neoadjuvant therapy for rectal cancer: are we dealing with an invisible margin? Dis Colon Rectum. 2012;55:1206-12.
https://doi.org/10.1097/DCR.0b013e318269fdb3
Rullier E, Rouanet P, Michot F, Mosnier H, Lelong B, Rivoire M, et al. Local versus rectal excision in downstaged low rectal cancer after radiochemotherapy: preliminary results of the randomized GRECCAR 2 trial (NCT00427375). Colorectal Disease J. 2013;15(s3):4-12.
Nyasavajjala SM, Shaw AG, Khan AQ, Brown SR, Lund JN. Neo-adjuvant chemo- radiotherapy and rectal cancer: can the UK watch and wait with Brazil? Colorectal Disease. 2010;12:33-6.
https://doi.org/10.1111/j.1463-1318.2009.02054.x
Perez RO, Habr-Gama A, São Julião GP, Gama-Rodrigues J, Sousa Jr AH, Campos FG, et al. Optimal timing for assessment of tumor response to neoadjuvant chemoradiation in patients with rectal cancer: do all patients benefit from waiting longer than 6w? Int J Rad Oncol Biol Phys. 2012;84(5):1159-65.
https://doi.org/10.1016/j.ijrobp.2012.01.096
Lefevre JH, Rousseau A, Svrcek M, Parc Y, Simon T, Tiret E. French Research Group of Rectal Cancer Surgery (GRECCAR). 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.
https://doi.org/10.1186/1471-2407-13-417
Palma P, Cuadros M, Conde-Muíño R, Olmedo C, Cano C, Segura Jiménez I, et al. Microarray profiling of mononuclear peripheral blood cells identifies novel candidate genes related to chemoradiation response in rectal cancer. PLoS One. 2013;8(9):e74034.
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