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Erschienen in: International Journal of Clinical Oncology 4/2018

24.02.2018 | Original Article

Impact of RAS/BRAF mutation status in locally advanced rectal cancer treated with preoperative chemotherapy

verfasst von: Taihei Oshiro, Keisuke Uehara, Toshisada Aiba, Toshiki Mukai, Tomoki Ebata, Masato Nagino

Erschienen in: International Journal of Clinical Oncology | Ausgabe 4/2018

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Abstract

Purpose

Our sincere hope is to establish the predictive factors of neoadjuvant chemotherapy (NAC) response and provide patients with greater certainty regarding treatment outcomes. The aim of this study was to assess the response to NAC and survival in patients with locally advanced rectal cancer (LARC) according to their RAS/BRAF mutation status.

Methods

Data on 57 patients with LARC who received NAC between 2009 and 2016 were analyzed retrospectively. The patients were classified into two groups based on their mutation status: wild-type in both RAS and BRAF (WT) or mutant-type in either RAS or BRAF (MT).

Results

Twenty-three patients were classified as WT, and the remaining 34 patients were MT. Histological response to NAC was similar in both groups. In responders, the 3-year relapse-free survival (RFS) was better compared with the non-responders (92 and 66%, respectively). In the WT group, the 3-year RFS was 95% which was significantly better than that in the MT group (59%, p = 0.011). The MT group was further subdivided into the following 2 groups by the pathological response; the MT responders (n = 10) and MT non-responders (n = 24). The 3-year RFS was 50% in the MT non-responders, which was significantly worse compared to that in the remaining patients (92%, p = 0.001).

Conclusion

RAS/BRAF mutations did not affect the response to NAC. However, the RFS was likely to be poor for those in the MT group who did not achieve favorable pathological response. In contrast, the RFS was favorable in the WT group regardless of the pathological response.
Literatur
1.
Zurück zum Zitat Fernandez-Martos C, Garcia-Albeniz X, Pericay C et al (2015) Chemoradiation, surgery and adjuvant chemotherapy versus induction chemotherapy followed by chemoradiation and surgery: long-term results of the Spanish GCR-3 phase II randomized trialdagger. Ann Oncol 26:1722–1728CrossRefPubMed Fernandez-Martos C, Garcia-Albeniz X, Pericay C et al (2015) Chemoradiation, surgery and adjuvant chemotherapy versus induction chemotherapy followed by chemoradiation and surgery: long-term results of the Spanish GCR-3 phase II randomized trialdagger. Ann Oncol 26:1722–1728CrossRefPubMed
2.
Zurück zum Zitat Cercek A, Goodman KA, Hajj C et al (2014) Neoadjuvant chemotherapy first, followed by chemoradiation and then surgery, in the management of locally advanced rectal cancer. J Natl Comprehen Cancer NetwJNCCN 12:513–519CrossRef Cercek A, Goodman KA, Hajj C et al (2014) Neoadjuvant chemotherapy first, followed by chemoradiation and then surgery, in the management of locally advanced rectal cancer. J Natl Comprehen Cancer NetwJNCCN 12:513–519CrossRef
3.
Zurück zum Zitat Calvo FA, Sole CV, Serrano J et al (2014) Preoperative chemoradiation with or without induction oxaliplatin plus 5-fluorouracil in locally advanced rectal cancer. Long-term outcome analysis. Strahlenther Onkol 190:149–157CrossRefPubMed Calvo FA, Sole CV, Serrano J et al (2014) Preoperative chemoradiation with or without induction oxaliplatin plus 5-fluorouracil in locally advanced rectal cancer. Long-term outcome analysis. Strahlenther Onkol 190:149–157CrossRefPubMed
4.
Zurück zum Zitat Deng Y, Chi P, Lan P et al (2016) Modified FOLFOX6 with or without radiation versus fluorouracil and leucovorin with radiation in neoadjuvant treatment of locally advanced rectal cancer: initial results of the Chinese FOWARC multicenter, open-label, Randomized Three-Arm Phase III Trial. J Clin Oncol 34:3300–3307CrossRefPubMed Deng Y, Chi P, Lan P et al (2016) Modified FOLFOX6 with or without radiation versus fluorouracil and leucovorin with radiation in neoadjuvant treatment of locally advanced rectal cancer: initial results of the Chinese FOWARC multicenter, open-label, Randomized Three-Arm Phase III Trial. J Clin Oncol 34:3300–3307CrossRefPubMed
5.
Zurück zum Zitat Kamiya T, Uehara K, Nakayama G et al (2016) Early results of multicenter phase II trial of perioperative oxaliplatin and capecitabine without radiotherapy for high-risk rectal cancer: CORONA I study. Eur J Surg Oncol 42:829–835CrossRefPubMed Kamiya T, Uehara K, Nakayama G et al (2016) Early results of multicenter phase II trial of perioperative oxaliplatin and capecitabine without radiotherapy for high-risk rectal cancer: CORONA I study. Eur J Surg Oncol 42:829–835CrossRefPubMed
6.
Zurück zum Zitat Schrag D, Weiser MR, Goodman KA et al (2014) Neoadjuvant chemotherapy without routine use of radiation therapy for patients with locally advanced rectal cancer: a pilot trial. J Clin Oncol 32:513–518CrossRefPubMedPubMedCentral Schrag D, Weiser MR, Goodman KA et al (2014) Neoadjuvant chemotherapy without routine use of radiation therapy for patients with locally advanced rectal cancer: a pilot trial. J Clin Oncol 32:513–518CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Uehara K, Hiramatsu K, Maeda A et al (2013) Neoadjuvant oxaliplatin and capecitabine and bevacizumab without radiotherapy for poor-risk rectal cancer: N-SOG 03 Phase II trial. Jpn J Clin Oncol 43:964–971CrossRefPubMed Uehara K, Hiramatsu K, Maeda A et al (2013) Neoadjuvant oxaliplatin and capecitabine and bevacizumab without radiotherapy for poor-risk rectal cancer: N-SOG 03 Phase II trial. Jpn J Clin Oncol 43:964–971CrossRefPubMed
8.
Zurück zum Zitat Ludmir EB, Palta M, Willett CG et al (2017) Total neoadjuvant therapy for rectal cancer: an emerging option. Cancer 123:1497–1506CrossRefPubMed Ludmir EB, Palta M, Willett CG et al (2017) Total neoadjuvant therapy for rectal cancer: an emerging option. Cancer 123:1497–1506CrossRefPubMed
9.
Zurück zum Zitat Guillem JG, Chessin DB, Cohen AM et al (2005) Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer. Ann Surg 241:829–836CrossRefPubMedPubMedCentral Guillem JG, Chessin DB, Cohen AM et al (2005) Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer. Ann Surg 241:829–836CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Fokas E, Liersch T, Fietkau R et al (2014) Tumor regression grading after preoperative chemoradiotherapy for locally advanced rectal carcinoma revisited: updated results of the CAO/ARO/AIO-94 trial. J Clin Oncol 32:1554–1562CrossRefPubMed Fokas E, Liersch T, Fietkau R et al (2014) Tumor regression grading after preoperative chemoradiotherapy for locally advanced rectal carcinoma revisited: updated results of the CAO/ARO/AIO-94 trial. J Clin Oncol 32:1554–1562CrossRefPubMed
11.
Zurück zum Zitat Huebner M, Wolff BG, Smyrk TC et al (2012) Partial pathologic response and nodal status as most significant prognostic factors for advanced rectal cancer treated with preoperative chemoradiotherapy. World J Surg 36:675–683CrossRefPubMed Huebner M, Wolff BG, Smyrk TC et al (2012) Partial pathologic response and nodal status as most significant prognostic factors for advanced rectal cancer treated with preoperative chemoradiotherapy. World J Surg 36:675–683CrossRefPubMed
12.
Zurück zum Zitat Osumi H, Shinozaki E, Suenaga M et al (2016) RAS mutation is a prognostic biomarker in colorectal cancer patients with metastasectomy. Int J Cancer 139:803–811CrossRefPubMed Osumi H, Shinozaki E, Suenaga M et al (2016) RAS mutation is a prognostic biomarker in colorectal cancer patients with metastasectomy. Int J Cancer 139:803–811CrossRefPubMed
13.
Zurück zum Zitat Foltran L, De Maglio G, Pella N et al (2015) Prognostic role of KRAS, NRAS, BRAF and PIK3CA mutations in advanced colorectal cancer. Futur Oncol (London, England) 11:629–640CrossRef Foltran L, De Maglio G, Pella N et al (2015) Prognostic role of KRAS, NRAS, BRAF and PIK3CA mutations in advanced colorectal cancer. Futur Oncol (London, England) 11:629–640CrossRef
14.
Zurück zum Zitat Vincenzi B, Cremolini C, Sartore-Bianchi A et al (2015) Prognostic significance of K-Ras mutation rate in metastatic colorectal cancer patients. Oncotarget 6:31604–31612PubMedPubMedCentral Vincenzi B, Cremolini C, Sartore-Bianchi A et al (2015) Prognostic significance of K-Ras mutation rate in metastatic colorectal cancer patients. Oncotarget 6:31604–31612PubMedPubMedCentral
15.
Zurück zum Zitat Venderbosch S, Nagtegaal ID, Maughan TS et al (2014) Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies. Clin Cancer Res 20:5322–5330CrossRefPubMedPubMedCentral Venderbosch S, Nagtegaal ID, Maughan TS et al (2014) Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies. Clin Cancer Res 20:5322–5330CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Nakamura H, Yokoyama Y, Uehara K et al (2016) The effects of bevacizumab on intestinal anastomotic healing in rabbits. Surg Today 46:1456–1463CrossRefPubMed Nakamura H, Yokoyama Y, Uehara K et al (2016) The effects of bevacizumab on intestinal anastomotic healing in rabbits. Surg Today 46:1456–1463CrossRefPubMed
17.
Zurück zum Zitat Yoshioka Y, Uehara K, Ebata T et al (2014) Postoperative complications following neoadjuvant bevacizumab treatment for advanced colorectal cancer. Surg Today 44:1300–1306CrossRefPubMed Yoshioka Y, Uehara K, Ebata T et al (2014) Postoperative complications following neoadjuvant bevacizumab treatment for advanced colorectal cancer. Surg Today 44:1300–1306CrossRefPubMed
18.
Zurück zum Zitat Watanabe T, Muro K, Ajioka Y et al (2018) Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol 23:1–34CrossRefPubMed Watanabe T, Muro K, Ajioka Y et al (2018) Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol 23:1–34CrossRefPubMed
19.
Zurück zum Zitat Dworak O, Keilholz L, Hoffmann A (1997) Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis 12:19–23CrossRefPubMed Dworak O, Keilholz L, Hoffmann A (1997) Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis 12:19–23CrossRefPubMed
20.
Zurück zum Zitat Farina-Sarasqueta A, van Lijnschoten G, Moerland E et al (2010) The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients. Ann Oncol 21:2396–2402CrossRefPubMed Farina-Sarasqueta A, van Lijnschoten G, Moerland E et al (2010) The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients. Ann Oncol 21:2396–2402CrossRefPubMed
21.
Zurück zum Zitat Gavin PG, Colangelo LH, Fumagalli D et al (2012) Mutation profiling and microsatellite instability in stage II and III colon cancer: an assessment of their prognostic and oxaliplatin predictive value. Clin Cancer Res 18:6531–6541CrossRefPubMedPubMedCentral Gavin PG, Colangelo LH, Fumagalli D et al (2012) Mutation profiling and microsatellite instability in stage II and III colon cancer: an assessment of their prognostic and oxaliplatin predictive value. Clin Cancer Res 18:6531–6541CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Sinicrope FA, Shi Q, Smyrk TC et al (2015) Molecular markers identify subtypes of stage III colon cancer associated with patient outcomes. Gastroenterology 148:88–99CrossRefPubMed Sinicrope FA, Shi Q, Smyrk TC et al (2015) Molecular markers identify subtypes of stage III colon cancer associated with patient outcomes. Gastroenterology 148:88–99CrossRefPubMed
23.
Zurück zum Zitat Chow OS, Kuk D, Keskin M et al (2016) KRAS and combined KRAS/TP53 mutations in locally advanced rectal cancer are independently associated with decreased response to neoadjuvant therapy. Ann Surg Oncol 23:2548–2555CrossRefPubMedPubMedCentral Chow OS, Kuk D, Keskin M et al (2016) KRAS and combined KRAS/TP53 mutations in locally advanced rectal cancer are independently associated with decreased response to neoadjuvant therapy. Ann Surg Oncol 23:2548–2555CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Martellucci J, Alemanno G, Castiglione F et al (2015) Role of KRAS mutation as predictor of pathologic response after neoadjuvant chemoradiation therapy for rectal cancer. Updates Surg 67:47–53CrossRefPubMed Martellucci J, Alemanno G, Castiglione F et al (2015) Role of KRAS mutation as predictor of pathologic response after neoadjuvant chemoradiation therapy for rectal cancer. Updates Surg 67:47–53CrossRefPubMed
25.
Zurück zum Zitat Duldulao MP, Lee W, Nelson RA et al (2013) Mutations in specific codons of the KRAS oncogene are associated with variable resistance to neoadjuvant chemoradiation therapy in patients with rectal adenocarcinoma. Ann Surg Oncol 20:2166–2171CrossRefPubMedPubMedCentral Duldulao MP, Lee W, Nelson RA et al (2013) Mutations in specific codons of the KRAS oncogene are associated with variable resistance to neoadjuvant chemoradiation therapy in patients with rectal adenocarcinoma. Ann Surg Oncol 20:2166–2171CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Clancy C, Burke JP, Coffey JC (2013) KRAS mutation does not predict the efficacy of neo-adjuvant chemoradiotherapy in rectal cancer: a systematic review and meta-analysis. Surg Oncol 22:105–111CrossRefPubMed Clancy C, Burke JP, Coffey JC (2013) KRAS mutation does not predict the efficacy of neo-adjuvant chemoradiotherapy in rectal cancer: a systematic review and meta-analysis. Surg Oncol 22:105–111CrossRefPubMed
27.
Zurück zum Zitat Gaedcke J, Grade M, Jung K et al (2010) KRAS and BRAF mutations in patients with rectal cancer treated with preoperative chemoradiotherapy. Radiother Oncol 94:76–81CrossRefPubMed Gaedcke J, Grade M, Jung K et al (2010) KRAS and BRAF mutations in patients with rectal cancer treated with preoperative chemoradiotherapy. Radiother Oncol 94:76–81CrossRefPubMed
28.
Zurück zum Zitat Derbel O, Wang Q, Desseigne F et al (2013) Impact of KRAS, BRAF and PI3KCA mutations in rectal carcinomas treated with neoadjuvant radiochemotherapy and surgery. BMC Cancer 13:200CrossRefPubMedPubMedCentral Derbel O, Wang Q, Desseigne F et al (2013) Impact of KRAS, BRAF and PI3KCA mutations in rectal carcinomas treated with neoadjuvant radiochemotherapy and surgery. BMC Cancer 13:200CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Uehara K, Nagino M (2016) Neoadjuvant treatment for locally advanced rectal cancer: a systematic review. Surg Today 46:161–168CrossRefPubMed Uehara K, Nagino M (2016) Neoadjuvant treatment for locally advanced rectal cancer: a systematic review. Surg Today 46:161–168CrossRefPubMed
30.
Zurück zum Zitat Glynne-Jones R, Hava N, Goh V et al (2015) Bevacizumab and combination chemotherapy in rectal cancer until surgery (BACCHUS): a phase II, multicentre, open-label, randomised study of neoadjuvant chemotherapy alone in patients with high-risk cancer of the rectum. BMC Cancer 15:764CrossRefPubMedPubMedCentral Glynne-Jones R, Hava N, Goh V et al (2015) Bevacizumab and combination chemotherapy in rectal cancer until surgery (BACCHUS): a phase II, multicentre, open-label, randomised study of neoadjuvant chemotherapy alone in patients with high-risk cancer of the rectum. BMC Cancer 15:764CrossRefPubMedPubMedCentral
Metadaten
Titel
Impact of RAS/BRAF mutation status in locally advanced rectal cancer treated with preoperative chemotherapy
verfasst von
Taihei Oshiro
Keisuke Uehara
Toshisada Aiba
Toshiki Mukai
Tomoki Ebata
Masato Nagino
Publikationsdatum
24.02.2018
Verlag
Springer Japan
Erschienen in
International Journal of Clinical Oncology / Ausgabe 4/2018
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-018-1253-z

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