Cetuximab in small bowel adenocarcinoma: a new friend?

Santini, Daniele; Fratto, Maria Elisabetta; Spoto, Chiara; Russo, Andrea; Galluzzo, Sara; Zoccoli, Alice; Vincenzi, Bruno; Tonini, Giuseppe

doi:10.1038/sj.bjc.6605898

Cited by 36 publications

(30 citation statements)

References 7 publications

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“…6 Recently, several case reports have described the effect of anti-EGFR therapy in patients with wild-type KRAS small intestinal adenocarcinomas. 7,8 Moreover, a number of studies of combined treatments, such as CAPOX (capecitabine and oxaliplatin) with bevacizumab, CAPOX with irinotecan, CAPOX with panitumumab, GEMOX (gemcitabine and oxaliplatin) with erlotinib and Nab-paclitaxel, are exploring the effects of anti-EGFR agents in small intestinal adenocarcinoma. 9 BRAF mutations, which always occur in the absence of KRAS mutations, have also been associated with resistance to anti-EGFR treatment in colorectal cancers.…”

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confidence: 99%

Clinicopathologic and prognostic associations of KRAS and BRAF mutations in small intestinal adenocarcinoma

Jun

Kim

et al. 2016

Modern Pathology

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Activating KRAS and/or BRAF mutations have been identified as predictors of resistance to anti-epidermal growth factor receptor (EGFR) chemotherapy in colorectal cancer. But the status of KRAS and BRAF mutations and their clinicopathologic and prognostic significance has not been extensively evaluated in small intestinal adenocarcinomas. In this work, the KRAS and BRAF genes in 190 surgically resected small intestinal adenocarcinoma cases were sequenced and their association with various clinicopathologic variables, including survival of the patients, was analyzed. KRAS or BRAF mutations were observed in 63 (33%) cases. Sixty-one cases had KRAS mutations and 2 had BRAF mutations and the two types of mutation were mutually exclusive. The majority of KRAS mutations were G4A transition (43/61 cases, 71%) or p.G12D (31/61 cases, 51%). The patients with mutant KRAS tended to have higher pT classifications (P = 0.034) and more frequent pancreatic invasion (P = 0.020) than those with wild-type KRAS. Multivariate logistic regression analysis showed that certain mutated KRAS subtypes (G4A transitions and G12D mutations) were significantly correlated with higher pT classification (P = 0.015 and 0.004, respectively) than wild-type KRAS and other KRAS mutations. The patients with KRAS or BRAF mutation had a tendency to shorter overall survival than those with wild-type KRAS and BRAF (P = 0.148), but subgroup analysis demonstrated the patients with KRAS mutations showed worse survival (median, 46.0 months; P = 0.046) than those with wild-type KRAS (85.4 months) in lower pT classification (pT1-pT3) group. In summary, KRAS and, infrequently, BRAF mutations are observed in a subset of small intestinal adenocarcinomas, and are associated with higher pT classification and more frequent pancreatic invasion. KRAS mutation is a poor prognostic predictor in patients with lower pT classification tumors. Anti-EGFR targeted therapy could be applied to about two-thirds of small intestinal adenocarcinoma patients, namely those with wildtype KRAS and BRAF if they have metastatic disease, similar to colorectal cancer patients.

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confidence: 99%

Clinicopathologic and prognostic associations of KRAS and BRAF mutations in small intestinal adenocarcinoma

Jun

Kim

et al. 2016

Modern Pathology

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“…A new chance for treatment is provided by targeted therapy using human monoclonal antibodies (cetuximab, bewacizumab), that possess high affinity and specificity for the epidermal growth factor receptor (EGFR). A handful of case reports have also described responses to anti-EGFR therapy in SBA patients with KRAS wild-type tumours [1,5,15]. The SBA treatment protocol is nevertheless still vague, mainly due to the low prevalence of SBA and too few prospective clinical trials [10].…”

Section: Discussionmentioning

confidence: 99%

Small bowel adenocarcinoma (SBA) — a case report

Polczyk

2017

Nowotwory. Journal of Oncology

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Backround. Small bowel cancers account for less than 0.5% of all malignancies and approximately 1-3% of gastrointestinal tract malignancies. The two major tumour types are carcinoid and adenocarcinoma. The latter is most commonly found in the duodenum and jejunum, but least often in the ileum. Case presentation. We present a case study of a 67-year-old woman with small bowel adenocarcinoma (SBA) of the ileum. The patient was admitted to the hospital with nonspecific, persistent, recurrent pain in her upper abdomen and with suspected subileus. Previously performed clinical investigation (i.e. colonoscopy, computed tomography scans -CT scans, small bowel follow-through) didn't reveal any abnormalities. At laparotomy we discovered a round mass obstructing the ileal lumen at about 40 cm from the Bauhin valve. A tumour was then resected within its surgical margins. Pathologic examination revealed an ileal adenocarcinoma and an infiltration of the local adipose tissue (Adenocarcinoma G3 partim gelatinosum), with no evidence of metastatic lesions in the lymph nodes nor into other organs (pT3N0M0; the clinical stage IIA). Further oncological treatment was thereby advised. Conclusions. A low prevalence and non-specific symptoms along without any clearly established diagnostic nor treatment protocols makes a final diagnosis difficult and thus merits further diagnostic investigation, particularly the testing of specific biochemical or immunological markers. NOWOTWORY J Oncol 2017; 67, 2: 137-141

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“…Standard therapies include CAPOX (capecitabine plus oxaliplatin), FOLFOX (5 FU, Leucovorin, and oxaliplatin), and FOLFIRI (5 FU, Leucovorin, and Irinotecan). Due to high-expression of VEGF and EGFR in SBA, there are reports of antitumor activity of anti-EGFR (Cetuximab) in certain cases of SBA [34][35][36][37][38]. Currently, prospective studies are ongoing exploring the efficacy of targeted therapies and role of adjuvant therapy and need to be followed closely [5,22,37].…”

Section: Neoadjuvant and Adjuvant Therapymentioning

confidence: 99%