Small bowel adenocarcinoma: A single center experience.

449 Background: Small bowel adenocarcinoma (SBA) represents only 2% of GI malignancies. There is limited data to guide clinical decisions, largely extrapolated from colorectal cancers (CRC). We evaluated treatment strategies and outcomes in patients (pts) with early and advanced SBA. Methods: We identified 56 pts with SBA diagnosed between 1/2005 - 1/2018 and treated at our institution. Demographics, pathological features, treatments, and molecular data were abstracted via medical record review. Data was analyzed with SAS statistical software. Results: Median age was 61, 54% male, site: duodenum (D 37.5%), duodenal ampula (A 17.9%), jejunum (J 19.6%), ileum (I 12.5 %), unknown (12.5%). Predisposing conditions were: IBD (6), Lynch (2), and Peutz-Jeghers syndromes (1). Stage (stg) at diagnosis was I (5%), II (20%), III (34%) and IV (41%). Primary tumor resection occurred in 33 pts: 21 received adjuvant chemotherapy, mostly FOLFOX; 17 developed metastatic disease. Treatment for metastatic SBA (n = 40) included 5FU-based chemotherapy without or with anti-VEGF (n = 18), or anti-EGFR therapies (n = 9). Median lines of therapy was 2 (range 1-7). For pts with stg I-III SBA, median DFS/OS was 21/38 mos. For stg IV pts, OS was 19.8 mos; 18/35/8/14 mos for D, A, J and I, respectively. Molecular biomarkers with targeted (28) or next generation sequencing (10) were available for 28 metastatic SBA pts: KRAS MUT (8), TP53 MUT (5), ERBB2 MUT (2), MSI-H (2), ERBB2, CCNE1 amplification (1 each), and NRAS, BRAF, CDKN2A, ERBB3, ATM, PIK3CA MUT (1 each). OS was 20 vs 19 mos for pts with KRAS WT vs MUT stg IV SBA, respectively. Among 16 pts with KRAS WT SBA, OS for those treated (9) or not (7) with anti-EGFR antibodies was 25 mos vs 21 mos. One pt with KRAS WT, ERBB2 amplification/ERBB2 V777L activating mutation is alive 5yrs+ from stg IV diagnosis on anti-EGFR plus chemotherapy (best response was 4 mos SD with trastuzumab/pertuzumab). Conclusions: This retrospective study demonstrates heterogeneity among SBA, overall inferior outcomes compared to CRC pts, and emphasizes genomic alterations which could be exploited therapeutically. Randomized studies for KRAS WT SBA pts should test the benefit from anti-EGFR targeted therapies in this rare tumor type.

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P-0149 Small Bowel Adenocarcinoma: A Single Center Experience

Annals of Oncology ◽

10.1016/s0923-7534(20)30070-3 ◽

2012 ◽

Vol 23 ◽

pp. iv73-iv74

Author(s):

Feriel Lylia Messekher ◽

Julie Carrier

Keyword(s):

Small Bowel ◽

Small Bowel Adenocarcinoma ◽

Single Center ◽

Single Center Experience

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Chemotherapy in Small Bowel Adenocarcinoma Associated with Celiac Disease: A Report of Three Cases

Tumori Journal ◽

10.1177/030089160308900217 ◽

2003 ◽

Vol 89 (2) ◽

pp. 193-195 ◽

Cited By ~ 4

Author(s):

Anna Cecilia Bettini ◽

Giordano D Beretta ◽

Pierluigi Sironi ◽

Stefania Mosconi ◽

Roberto Labianca

Keyword(s):

Small Intestine ◽

Celiac Disease ◽

Small Bowel ◽

Genetic Disease ◽

Intestinal Inflammation ◽

Chemotherapy Regimen ◽

Tumor Resection ◽

Small Bowel Adenocarcinoma ◽

Chronic Intestinal Inflammation

Tumors of the small intestine are rare and usually occur in association with genetic disease and chronic intestinal inflammation. We report three cases of small bowel adenocarcinoma in patients affected by celiac disease who received a safe chemotherapy regimen (FOLFOX IV or LV5FU2) after tumor resection.

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ERBB3-Activating Mutations in Small Bowel Adenocarcinomas

JCO Precision Oncology ◽

10.1200/po.17.00243 ◽

2018 ◽

pp. 1-9

Author(s):

Luc Cabel ◽

Thomas Aparicio ◽

Ivan Bieche ◽

Magali Svrcek ◽

Aziz Zaanan ◽

...

Keyword(s):

Next Generation Sequencing ◽

Small Bowel ◽

High Rate ◽

Clinical Activity ◽

Tumor Type ◽

Small Bowel Adenocarcinoma ◽

Next Generation ◽

Targeted Next Generation Sequencing ◽

Activating Mutations ◽

Generation Sequencing

Purpose Functional studies have demonstrated that some mutations of ERBB3, which encodes for human epidermal growth factor receptor (HER) 3, are oncogenic via activation of the ErbB family signaling pathway. Significant clinical activity of anti-HER2 therapies (trastuzumab plus lapatinib combination or afatinib) has been reported in patients with ERBB3-mutated cancers. This study was designed to report the rate of activating ERBB3 mutations in small bowel adenocarcinoma (SBA), a rare tumor type in which we previously reported a high rate (12%) of ERBB2-activating mutations. Materials and Methods DNA from 74 SBAs, previously characterized for ERBB2 mutations and mismatch repair status, was submitted for sequencing of ERBB3 exons 3, 6, 7, 8, and 23. Orthogonal validation by targeted next-generation sequencing was performed. Results Four of 74 SBAs (5.4%) displayed ERBB3-activating mutations, including three p.V104M mutations (c.310 G>A) in exon 3 and one p.E928G mutation (c.2783 A>G) in exon 23. No mutations were detected in exons 6, 7, and 8. ERBB3-activating mutations were associated with microsatellite instability ( P = .002) and the presence of ERBB2-activating mutations ( P = .002). Two SBAs with co-occurrence of ERBB2 and ERBB3 mutations were further analyzed by targeted next-generation sequencing. Mutant allelic frequencies suggested that both mutations were shared by the same clone rather than being harbored by mutually exclusive tumor subclones. Conclusion SBAs display a high rate of ERBB3-activating mutations, which have been shown to be targetable by anti-HER2 therapies. Strikingly, ERBB3 was frequently comutated with ERBB2, suggesting a strong oncogenic addiction of these SBAs to the HER2 pathway.

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Case Report: Molecular Features and Treatment Options for Small Bowel Adenocarcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.593561 ◽

2021 ◽

Vol 11 ◽

Author(s):

Miguel Cordova-Delgado ◽

Gonzalo Pizarro ◽

Mauricio P. Pinto ◽

Maria Elisa Herrera ◽

Marcelo Garrido

Keyword(s):

Small Bowel ◽

Treatment Options ◽

Stage Iv ◽

Tumor Type ◽

Small Bowel Adenocarcinoma ◽

Molecular Alterations ◽

Molecular Features ◽

Genetic Landscape ◽

Rare Malignancy ◽

Gene Alterations

Small bowel adenocarcinoma (SBA) is a rare malignancy characterized by poor prognosis. Recent efforts have sought to elucidate the genetic landscape and the molecular drivers behind this disease. Herein, we report the main molecular alterations in two metastatic (stage IV) SBA patients. Interestingly, one of them had gene alterations that affected signaling pathways previously described for SBA. However, a second patient displayed previously unreported alterations in this particular tumor type. Based on these findings we discuss potential treatment options for patients affected by this rare, aggressive disease.

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Rare but Real: Management of Small Bowel Adenocarcinoma

American Society of Clinical Oncology Educational Book ◽

10.14694/edbook_am.2013.33.189 ◽

2013 ◽

pp. 189-193 ◽

Cited By ~ 1

Author(s):

Michael J. Overman

Keyword(s):

Clinical Trials ◽

Small Bowel ◽

Clinical Symptoms ◽

Advanced Disease ◽

Tumor Type ◽

Small Bowel Adenocarcinoma ◽

Phase Ii Studies ◽

Prospective Phase ◽

Bowel Imaging

Despite representing the longest segment of the alimentary tract, small bowel adenocarcinomas are rare. The diagnosis of small bowel adenocarcinoma is frequently delayed because of the nonspecific clinical symptoms and the limitations of small bowel imaging. The majority of patients will present with either lymph node or distant metastatic disease. Though the role of adjuvant therapy for resected small bowel adenocarcinoma is unclear, recent research efforts have led to an improvement in our management of advanced disease. Prospective phase II studies have successfully enrolled patients with this rare tumor type and have established the combination of a fluoropyrimidine and oxaliplatin as the most appropriate front-line chemotherapy for patients with advanced disease. Currently, five prospective clinical trials have been designed for patients with small bowel adenocarcinoma and enrollment to these clinical trials should be encouraged.

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A Trial to Evaluate the Potential Benefit of Adjuvant Chemotherapy for Small Bowel Adenocarcinoma

Case Medical Research ◽

10.31525/ct1-nct04257461 ◽

2020 ◽

Author(s):

Keyword(s):

Adjuvant Chemotherapy ◽

Small Bowel ◽

Potential Benefit ◽

Small Bowel Adenocarcinoma

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Receptor tyrosine kinase gene amplification is predictive of intraoperative seizures during glioma resection with functional mapping

Journal of Neurosurgery ◽

10.3171/2018.12.jns182700 ◽

2020 ◽

Vol 132 (4) ◽

pp. 1017-1023 ◽

Cited By ~ 2

Author(s):

Bryan D. Choi ◽

Daniel K. Lee ◽

Jimmy C. Yang ◽

Caroline M. Ayinon ◽

Christine K. Lee ◽

...

Keyword(s):

Tyrosine Kinases ◽

Univariate Analysis ◽

Tumor Resection ◽

Tumor Grade ◽

Molecular Data ◽

Genetic Alterations ◽

Functional Mapping ◽

Chi Square ◽

Kinase Gene ◽

Glioma Resection

OBJECTIVEIntraoperative seizures during craniotomy with functional mapping is a common complication that impedes optimal tumor resection and results in significant morbidity. The relationship between genetic mutations in gliomas and the incidence of intraoperative seizures has not been well characterized. Here, the authors performed a retrospective study of patients treated at their institution over the last 12 years to determine whether molecular data can be used to predict the incidence of this complication.METHODSThe authors queried their institutional database for patients with brain tumors who underwent resection with intraoperative functional mapping between 2005 and 2017. Basic clinicopathological characteristics, including the status of the following genes, were recorded: IDH1/2, PIK3CA, BRAF, KRAS, AKT1, EGFR, PDGFRA, MET, MGMT, and 1p/19q. Relationships between gene alterations and intraoperative seizures were evaluated using chi-square and two-sample t-test univariate analysis. When considering multiple predictive factors, a logistic multivariate approach was taken.RESULTSOverall, 416 patients met criteria for inclusion; of these patients, 98 (24%) experienced an intraoperative seizure. Patients with a history of preoperative seizure and those treated with antiepileptic drugs prior to surgery were less likely to have intraoperative seizures (history: OR 0.61 [95% CI 0.38–0.96], chi-square = 4.65, p = 0.03; AED load: OR 0.46 [95% CI 0.26–0.80], chi-square = 7.64, p = 0.01). In a univariate analysis of genetic markers, amplification of genes encoding receptor tyrosine kinases (RTKs) was specifically identified as a positive predictor of seizures (OR 5.47 [95% CI 1.22–24.47], chi-square = 5.98, p = 0.01). In multivariate analyses considering RTK status, AED use, and either 2007 WHO tumor grade or modern 2016 WHO tumor groups, the authors found that amplification of the RTK proto-oncogene, MET, was most predictive of intraoperative seizure (p < 0.05).CONCLUSIONSThis study describes a previously unreported association between genetic alterations in RTKs and the occurrence of intraoperative seizures during glioma resection with functional mapping. Future models estimating intraoperative seizure risk may be enhanced by inclusion of genetic criteria.

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Preservation of nasal turbinates in endoscopic, anterior skull base surgery—yes, we can!

European Archives of Oto-Rhino-Laryngology ◽

10.1007/s00405-021-06856-9 ◽

2021 ◽

Author(s):

Axel Wolf ◽

Alexandros Andrianakis ◽

Peter Valentin Tomazic ◽

Michael Mokry ◽

Georg Clarici ◽

...

Keyword(s):

Skull Base ◽

Skull Base Surgery ◽

Tumor Resection ◽

Tumor Location ◽

Anterior Skull Base ◽

Tumor Diameter ◽

Tumor Type ◽

Preoperative Information ◽

Medical University ◽

Significant Factors

Abstract Objective To evaluate the frequency, type and indications of nasal turbinate (NT) resection during endoscopic, anterior skull base surgery and to analyze factors that may have an impact on the need of NT removal. Methods In this retrospective cohort study, 306 subjects (150 males and 156 females, mean age 55.4 ± 15.3 years) who underwent multidisciplinary, transnasal, endoscopic tumor surgery of the anterior skull base using 4-handed techniques between 2011 and 2019 at the Department of Otorhinolaryngology, Medical University of Graz, were included. Results In the majority of interventions (n = 281/306; 91.8%), all NT were preserved. Significant factors influencing the need of NT resections turned out to be type of endoscopic approach (p < 0.001; V = 0.304), sagittal (p = 0.003; d = 0.481) and transversal (p = 0.017; d = 0.533) tumor diameter, tumor type (p < 0.001; V = 0.355) and tumor location (p < 0.001; V = 0.324). Conclusions NT can be preserved in the majority of patients undergoing tumor resection in anterior, transnasal, skullbase surgery and routine resection of NT should be avoided. Variables that have an impact on the need of NT resections are types of endoscopic approaches, sagittal and transversal tumor extension and tumor type. These factors should be considered in planning of surgery and preoperative information of patients.

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