IMPACT OF GENETICS ON NEOADJUVANT THERAPY WITH COMPLETE PATHOLOGICAL RESPONSE IN METASTATIC COLORECTAL CANCER: CASE REPORT AND REVIEW OF THE LITERATURE
Bulajic P1, Bidzic N1,*, Djordjevic V1, Ceranic M1,2, Basaric D1,2, Pesic V3, Djordjevic-Pesic J4
*Corresponding Author: Nemanja Bidzic, M.D., Clinic for Digestive Surgery, Clinical Center of Serbia, Koste Todorovica 6, Belgrade 11000, Serbia. Tel. +381-11-306-5957. Fax: +381-11-306-5967. E-mail: nemanja bidzic@yahoo.com
page: 1

DISCUSSION

Today standard therapy for metastatic colorectal cancer certainly comprise both surgery and chemotherapy. Outcomes of surgery alone include death in almost 30.0% of patients during the first 2 years. Chemotherapy has not yet achieved a long-term cure [2,4], hence, surgery is still necessary for cure. With combined treatment, more than 50.0% of the patients can reach a 5-year survival and up to 25.0% 10-year survival [12]. Even then, the recurrence rate is high, and about 75.0% of all recurrences are seen in the first 2 years [2]. Chemotherapy can prolong recurrence-free survival [4,13], increase resectability of liver metastases [14] and has an impact on overall survival [15]. Different regimens of cytotoxic agents are in use (FOLFOX, CAPOX, FOLFIRI, and FOLFOXIRI). New biological therapy added to cytotoxic regimens may enhance therapeutic efficiency, especially in the neoadjuvant setting [16,17]. Chemotherapy, with or without targeted therapy, is recommended for synchronous colorectal liver metastases because they have a less favorable cancer biology [13,16] and expected survival than metachronous, particularly in late metachronous metastases [2]. It is of great importance to identify patients at-risk of recurrence and the patients who will receive a benefit from neoadjuvant therapy. Earlier clinical and pathological risk scores are used to estimate prognosis after surgery and to evaluate eligibility for surgery [4]. In the era of modern systemic chemotherapy regimens, these risk scores have low efficiency in clinical decision-making [18,19]. Colorectal cancer is a heterogeneous disease with several possible pathways responsible for carcinogenesis and a lot of genetic mutations. Different genetic and chromosomal alterations are described: microsatellite instability, loss of heterozygosity of chromosome 18, mutations in p53, RAS and RAF mutations (9). Thus, various tumor biology is possible and subsequently, different responses to neoadjuvant therapy. Molecular biomarkers are now being incorporated in risk stratification and treatment decision due to developing a personalized or individualized treatment [20]. Testing of cancer genetic profile has a leading role in the new concept of personalized medicine, and some of these are widely accepted and frequently used in molecular targeted therapy [21]. Evaluated molecular targeted therapy for metastatic colorectal cancer includes Bevacizumab and Cetuximab. Bevacizumab is a monoclonal antibody inhibitor of VEGF, which is the product of the same-named gene and has a crucial role in angiogenesis and tumor growth [7,8]. Cetux- imab is a monoclonal antibody inhibitor of epidermal growth factor receptor (EGFR) which is very effective in the therapy of KRAS wild-type cancers but with no effect on KRAS mutations [6,21], except in the specific mutation on codon 13 (G13D), which is probably associated with some response to Cetuximab [22]. In the present case, we detected a mutation on codon 13 but without differentiation of the exact mutation type, and we did not know if it was a G13D mutation. Even then, the results of recent studies were not so strong to incorporate the Cetuximab for G13D, especially in a neoadjuvant setting [22]. We decided to use cytotoxic neoadjuvant therapy (CAPOX) and to add Bevacizumab as the only remaining biological agent for colorectal liver metastases, which were previously evaluated as a potent neoadjuvant regimen. There is a possibility for estimation of VEGF expression in the tumor sample, but in our oncological practice it is not routinely used for colorectal cancer as the majority of patients have good therapeutic results [8,16,17]. After seven cycles of CAPOX and Bevacizumab, we achieved an extraordinary response: more than 70.0% regression of metastatic lesions and complete regression of the primary tumor, according to RECIST. Carcinoembryonic antigen and CA19-9 were normal. Postoperative histopathology revealed complete primary and secondary tumor response without any evidence of malignancy [Figure 1(l) and 1(m)]. The complete pathological response has been reported, but most of the authors have presented cases with staged surgery for synchronous metastatic disease and input neo-adjuvant treatment after resection of the primary tumor and before resection of secondary tumors [23-25]. In one case, it was even a reverse or liver-first approach but also achieving complete response in primary and metastatic tumors [26]. The primary tumor was locally advanced (cT3d/4, N2) and surgery as a first-line treatment would not be a proper decision because of the risk of local recurrence. On the other hand, pelvic radiotherapy has a complete response in 10.0 to 20.0% cases but has many side effects [27]. In this case, we had to treat both primary and metastatic tumors and achieving a positive effect on neoadjuvant treatment we achieved a chance for a synchronous resection. Vanishing metastases and impossibility to detect liver lesions intraoperatively after neoadjuvant treatment have been described. The reason is the same echogenicity of the lesion and normal liver parenchyma [28]. Concordance between imaging and pathological examination particularly in bevacizumab-containing neoadjuvant therapy is poor and so visible lesions on imaging can be without malignant cells on histopathology [29]. Natural history of undetectable lesions after neoadjuvant chemotherapy in case of complete pathological response of the other lesions has not yet been elucidated. We performed CT scans, tumor markers and PET after 8 months and all pointed to recurrence-free status. Complete disappearance of primary and secondary lesions makes this case unique.



Number 22
VOL. 22, 2019 Accepted articles
Number 22
VOL. 22, 2019 Supplement
Number 21
VOL. 21(2), 2018
Number 21
VOL. 21 (1), 2018
Number 21
VOL. 21, 2018 Accepted articles
Number 21
VOL. 21, 2018 Supplement
Number 20
VOL. 20 (2), 2017
Number 20
VOL. 20 (1), 2017
Number 19
VOL. 19 (2), 2016
Number 19
VOL. 19 (1), 2016
Number 18
VOL. 18 (2), 2015
Number 18
VOL. 18 (1), 2015
Number 17
VOL. 17 (2), 2014
Number 17
VOL. 17 (1), 2014
Number 16
VOL. 16 (2), 2013
Number 16
VOL. 16 (1), 2013
Number 15
VOL. 15 (2), 2012
Number 15
VOL. 15, 2012 Supplement
Number 15
Vol. 15 (1), 2012
Number 14
14 - Vol. 14 (2), 2011
Number 14
The 9th Balkan Congress of Medical Genetics
Number 14
14 - Vol. 14 (1), 2011
Number 13
Vol. 13 (2), 2010
Number 13
Vol.13 (1), 2010
Number 12
Vol.12 (2), 2009
Number 12
Vol.12 (1), 2009
Number 11
Vol.11 (2),2008
Number 11
Vol.11 (1),2008
Number 10
Vol.10 (2), 2007
Number 10
10 (1),2007
Number 9
1&2, 2006
Number 9
3&4, 2006
Number 8
1&2, 2005
Number 8
3&4, 2004
Number 7
1&2, 2004
Number 6
3&4, 2003
Number 6
1&2, 2003
Number 5
3&4, 2002
Number 5
1&2, 2002
Number 4
Vol.3 (4), 2000
Number 4
Vol.2 (4), 1999
Number 4
Vol.1 (4), 1998
Number 4
3&4, 2001
Number 4
1&2, 2001
Number 3
Vol.3 (3), 2000
Number 3
Vol.2 (3), 1999
Number 3
Vol.1 (3), 1998
Number 2
Vol.3(2), 2000
Number 2
Vol.1 (2), 1998
Number 2
Vol.2 (2), 1999
Number 1
Vol.3 (1), 2000
Number 1
Vol.2 (1), 1999
Number 1
Vol.1 (1), 1998

 

 


 About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact
 Copyright © Balkan Journal of Medical Genetics 2006