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

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.

scholarly journals Small Bowel Adenocarcinoma, Version 1.2020, NCCN Clinical Practice Guidelines in Oncology

2019 ◽  
Vol 17 (9) ◽  
pp. 1109-1133 ◽  
Author(s):  
Al B. Benson ◽  
Alan P. Venook ◽  
Mahmoud M. Al-Hawary ◽  
Mustafa A. Arain ◽  
Yi-Jen Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Small Bowel ◽  
Treatment Options ◽  
Standard Of Care ◽  
Primary Treatment ◽  
Evidence Based ◽  
Small Bowel Adenocarcinoma ◽  
Advanced Stage ◽  
Nccn Guidelines ◽  
Rare Malignancy

Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract that has increased in incidence across recent years. Often diagnosed at an advanced stage, outcomes for SBA are worse on average than for other related malignancies, including colorectal cancer. Due to the rarity of this disease, few studies have been done to direct optimal treatment, although recent data have shown that SBA responds to treatment differently than colorectal cancer, necessitating a separate approach to treatment. The NCCN Guidelines for Small Bowel Adenocarcinoma were created to establish an evidence-based standard of care for patients with SBA. These guidelines provide recommendations on the workup of suspected SBA, primary treatment options, adjuvant treatment, surveillance, and systemic therapy for metastatic disease. Additionally, principles of imaging and endoscopy, pathologic review, surgery, radiation therapy, and survivorship are described.

scholarly journals Small Bowel Epithelial Precursor Lesions: A Focus on Molecular Alterations

2021 ◽  
Vol 22 (9) ◽  
pp. 4388
Author(s):  
Alessandro Vanoli ◽  
Federica Grillo ◽  
Daniela Furlan ◽  
Giovanni Arpa ◽  
Oneda Grami ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Small Bowel ◽  
Crohn's Disease ◽  
Cowden Syndrome ◽  
Intestinal Type ◽  
Precursor Lesions ◽  
Molecular Alterations ◽  
Molecular Features ◽  
Gastric Type ◽  
Small Intestinal

The wider use of gastrointestinal endoscopic procedures has led to an increased detection of small intestinal preneoplastic and neoplastic epithelial lesions, most of which are identified in the duodenum and ampullary region. Like their malignant counterparts, small intestinal glandular precursor lesions, which include adenomas and hamartomas, may arise sporadically or be associated with hereditary tumor syndromes, such as familial adenomatous polyposis, MUTYH-associated polyposis, Lynch syndrome, Peutz-Jeghers syndrome, juvenile polyposis syndrome, and Cowden syndrome. In addition, dysplastic, preinvasive lesions have been observed adjacent to small bowel adenocarcinomas complicating immune-related disorders, such as celiac or Crohn’s disease. Adenomatous lesions may exhibit an intestinal-type, gastric-type, or, very rarely, serrated differentiation, related to different molecular pathogenetic mechanisms. Finally, in the background of multiple endocrine neoplasia 1 syndrome, precursor neuroendocrine growths have been described. In this review we offer a comprehensive description on the histo-molecular features of the main histotypes of small bowel epithelial precursors lesions, including: (i) sporadic adenomas (intestinal-type and gastric-type; non-ampullary and ampullary); (ii) syndromic adenomas; (iii) small bowel dysplasia in celiac and Crohn’s disease; (iv) serrated lesions; (v) hamartomatous lesions; and (vi) neuroendocrine precursor lesions.

An atypical presentation of small bowel adenocarcinoma; a case report

2020 ◽  
pp. 1-9
Author(s):  
Warda Khalid ◽  
Danish Ali ◽  
Abdul Rehman ◽  
Muhammad Adeel Kaiser ◽  
Tausief Fatima ◽  
...  
Keyword(s):  
Small Bowel ◽  
Gastrointestinal Symptoms ◽  
Screening Tools ◽  
Small Bowel Adenocarcinoma ◽  
Atypical Presentation ◽  
Rare Entity ◽  
Histological Subtype ◽  
Clinical Detection ◽  
Rare Malignancy ◽  
Small Bowel Malignancy

Abstract Small bowel malignancy (SBM) is a rare malignancy in the gastrointestinal tract. Duodenum is the most commonly involved segment and the most common histological subtype is adenocarcinoma (40%). Due to a lack of screening tools and vague symptoms, its clinical detection is very challenging. A 27-year-old man presented at the surgical emergency of Lahore General Hospital in February 2019 with non-specific gastrointestinal symptoms (vomiting, abdominal pain), for which he had previously visited the hospital multiple times. Later, on further workup, he had been diagnosed as a case of intussusception on CT scan. On exploration, he had an impassable stricture in the jejunum. Resection anastomosis of the jejunum was done, but later, on histopathology it turned out to be adenocarcinoma. Adenocarcinoma of the small bowel is a rare entity, and, particularly in Pakistan, Continuous...  

Small bowel adenocarcinoma phenotyping and prognostic factors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3585-3585
Author(s):  
Thomas Aparicio ◽  
Magali Svrcek ◽  
Anais Laforest ◽  
Aziz Zaanan ◽  
Kanean Beohou ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Kras Mutation ◽  
Univariate Analysis ◽  
Stage Iv ◽  
Stage I ◽  
Disease Stage ◽  
Her2 Overexpression ◽  
Small Bowel Adenocarcinoma ◽  
Brafv600e Mutation ◽  
Molecular Alterations

3585 Background: SBA is a rare tumor with poor prognosis. Data regarding SBA molecular alterations are lacking. Methods: We searched for several candidate oncogenic alterations and characterised the immunophenotype according to the primary tumour location in pts with SBA (all stages; ampullary tumours excluded) treated in 11 centres from 1996 to 2008. Tissue microarrays were constructed from tumour samples, and DNA was extracted from formalin-fixed, paraffin-embedded samples. HER2, β-catenin, TP53, and mismatch repair (MMR) protein expression was assessed by immunohistochemistry. A molecular analysis assessed microsatellite instability, KRAS mutation and BRAFV600E mutation. Results: We obtained samples from 63 SBA pts (median age, 58 years; tumour stage: I-II, n=19 (30%); III, n=22 (35%); IV, n=20 (32%); locally advanced, n=2 (3%)). HER2 overexpression (3+) was observed in 2/62 (3%) pts. Overexpression of TP53 was observed in 26/62 (42%) pts. Abnormal expression of β-catenin was observed in 12/62 (19%) pts. MMR deficiency (dMMR) was observed in 14/61 (23%) pts, consistent with Lynch syndrome in 7/14 (50%) pts. All of the dMMR tumours were in duodenum or jejunum. Only one of dMMR tumour was stage IV. A KRAS mutation was observed in 21/49 (43%) pts. BRAFV600E mutation was observed in only 1/40 pt. Median overall survival (OS) was 36.6 months (95% confidence interval [CI], 26.9-72.2). In univariate analysis, stage I-II (p<0.001) and dMMR phenotype (p=0.02) were significantly associated with longer OS. In multivariate analysis, only disease stage independently predicted longer OS (p<0.001). For stage IV pts, median OS was 17.9 months (CI, 12.6-36.6). For stage I-III pts median recurrence-free survival (RFS) was 26.7 months (CI: 14.6-42.4). A trend for a better RFS was observed if tumour was dMMR HR: 0.39 (CI, 0.10-1.44], p=0.15. Conclusions: This large study suggests that molecular alterations in SBA are closer to those in colorectal cancer (CRC) than those in gastric cancer, with low levels of HER 2 overexpression and high rates of KRAS mutations. The seemingly higher rate of dMMR than in CRC may be explained by the higher frequency of Lynch syndrome in SBA in pts. A trend for good prognosis was associated with dMMR.

DNA mutation frequencies in metastatic small bowel adenocarcinoma (mSBA) in comparison to gastric (mGC), colon (mCC), and rectal cancer (mRC): Continuum or cutpoint?

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14636-e14636
Author(s):  
Janet E. Murphy ◽  
Andrea Lyn Russo ◽  
Jackie Szymonifka ◽  
Eunice Lee Kwak ◽  
Jill N. Allen ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Small Bowel ◽  
Stage Iv ◽  
Unknown Primary ◽  
Small Bowel Adenocarcinoma ◽  
Exact Test ◽  
Dna Mutation ◽  
Genotype Frequencies ◽  
Mutational Profiling ◽  
Significant Difference

e14636 Background: The small intestine is in continuity with the stomach and colon/rectum. However mGC and mCC/mRC differ in oncogene profiles. No study has evaluated the oncogene profile of mSBA on the continuum of mGC and mCC/mRC. This may give insight into biology and have implications for treatment. Methods: Respective analysis was performed on GI cancer patients who underwent tumor mutational profiling since 2010. Genotyping was performed on formalin-fixed and paraffin-embedded tumor tissue using a multiplexed mutational profiling platform. Here we report results for APC, BRAF, EGFR, IDH1, KRAS, NRAS, PI3K, PTEN, and TP53. Results: We identified 12 patients with mSBA (11/12 with clinical data, 11/12 with genotype data). Median age at stage IV diagnosis was 61.1y (49.3-71.5y). Four patients had duodenal, 3 jejeunal, 2 ileal, and 2 multiple/unknown primary sites. All patients received 5FU and ox, while 8/11 received irino, 5/11 bev, 3/11 cetux, 1/11 regorafenib and 1/11 capecitabine. Two patients had adjuvant RT (both duodenal) while 4/11 received palliative RT. Survival was calculated from the date of stage IV diagnosis until death, with data censored on 2/1/2013. Median survival was 24.0 months (95% CI 6.4 – 60.0 mo). We compared genotype frequencies of mSBA patients (11) with mGC (41), mCC (161), and mRC (64) using Fisher’s exact test for pairwise comparisons. Conclusions: While the small bowel sample size was small, a significant difference in KRAS mutation frequency was found when compared to gastric cancer. No significant differences in mutation frequencies were found when compared with colon or rectal cancer. [Table: see text]

Molecular profile of ampulla of vater carcinoma (AVC): A rare tumor type with meaningful molecular alterations.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4119-4119
Author(s):  
João Pinto ◽  
Helena Verdaguer ◽  
Maria Teresa Salcedo ◽  
Anna Pedrola ◽  
Jorge Hernando-Cubero ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Stage Iv ◽  
Molecular Profile ◽  
Tumor Type ◽  
Phase I Clinical Trials ◽  
Histological Subtypes ◽  
Rare Type ◽  
Molecular Alterations ◽  
Dismal Prognosis ◽  
Stage Iv Disease

4119 Background: AVC is a rare type of cancer with dismal prognosis and limited therapeutic options due to the lack of specific clinical trials. Two histologic subtypes predominate, namely pancreatobiliary and intestinal. A variety of molecular alterations have been described in AVC, but their clinical and therapeutic implications have not been studied in detail. Methods: Retrospective cohort study of patients (pts) diagnosed with AVC treated in our institution from 2010 to 2018. We routinely performed Next Generation Sequencing in all AVC tumors. Our main objectives were to describe the molecular profile of AVC and correlate with clinical outcomes. Results: Out of 26 pts with AVC, 13 pts were male (50%), median age 65 (range 43-83), 7 pts (27%) had stage IV disease at diagnosis. Histologic type was pancreatobiliary in 18 pts (69%), intestinal in 7 pts (27%) and mixed in one case (4%). We identified KRAS mutations (mut) in 10 pts (7 pancreatobiliary, 2 intestinal, 1 mixed), TP53 mut in 6 pts (4/1/1), PIK3CA mut in 3 pts (3/0/0), ERBB2 mut in 3 pts (2/1/0), CTNNB1 mut in 3 pts (2/1/0). In pancreatobiliary we found single cases with RNF43, BRCA1 and CHEK2 mut; while in intestinal we found single cases with NRAS and BRAF mut. One tumor of intestinal subtype had microsatellite instability (MSI). Three pts were included in phase I clinical trials, 2 of them with trials based on tumor profile (ERBB2 mut with pan-HER inhibitor and MSI with immunotherapy). Median overall survival (OS) was 21 months for pts with stage I, II and III disease (95% CI 12.37-not reached) and 13.2 months for stage IV disease at diagnosis (95% CI 5.73-not reached). In cox models, median OS was not dependent on KRAS or TP53 mutation status, or histological subtypes. Conclusions: AVC is a rare type of cancer with two differentiated histological subtypes harboring unique molecular alterations that can be matched to investigational therapies. A broader knowledge of the biology of these tumors is needed to improve patient outcomes.

scholarly journals Current Status and Future Targeted Therapy in Adrenocortical Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
George Alyateem ◽  
Naris Nilubol
Keyword(s):  
Systemic Therapy ◽  
Treatment Options ◽  
Molecular Profiling ◽  
Current Treatment ◽  
Current Status ◽  
Adrenocortical Cancer ◽  
Treatment Standards ◽  
Molecular Alterations ◽  
Complete Surgical Resection ◽  
Rare Malignancy

Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. The current treatment standards include complete surgical resection for localized resectable disease and systemic therapy with mitotane alone or in combination with etoposide, doxorubicin, and cisplatin in patients with advanced ACC. However, the efficacy of systemic therapy in ACC is very limited, with high rates of toxicities. The understanding of altered molecular pathways is critically important to identify effective treatment options that currently do not exist. In this review, we discuss the results of recent advanced in molecular profiling of ACC with the focus on dysregulated pathways from various genomic and epigenetic dysregulation. We discuss the potential translational therapeutic implication of molecular alterations. In addition, we review and summarize the results of recent clinical trials and ongoing trials.

scholarly journals Small Bowel Adenocarcinoma: Etiology, Presentation, and Molecular Alterations

2019 ◽  
Vol 17 (9) ◽  
pp. 1135-1141 ◽  
Author(s):  
Katrina S. Pedersen ◽  
Kanwal Raghav ◽  
Michael J. Overman
Keyword(s):  
Colorectal Cancer ◽  
Small Bowel ◽  
Patient Outcomes ◽  
Delayed Diagnosis ◽  
Small Bowel Adenocarcinoma ◽  
Rare Cancer ◽  
Molecular Alterations ◽  
Molecular Studies

Small bowel adenocarcinoma (SBA) is a rare cancer that has been treated similarly to colorectal cancer (CRC) in the advanced setting. Incidence has been increasing as detection efforts have been improving for these challenging-to-diagnose tumors, but patients frequently experience prolonged nonspecific symptoms due to delayed diagnosis. As a result of such delays and likely due to variant biology, patient outcomes for SBA are inferior to those for CRC at all stages of diagnosis. Recent molecular studies highlight the genomic differences underpinning these tumors and suggest new future pathways for treatment, distinct from CRC.

ERBB3-Activating Mutations in Small Bowel Adenocarcinomas

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.

Small bowel adenocarcinoma: A single center experience.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 449-449
Author(s):  
Lindsay Marie Hannan ◽  
William Proctor Harris ◽  
Veena Shankaran ◽  
Andrew L. Coveler ◽  
Colin Pritchard ◽  
...  
Keyword(s):  
Small Bowel ◽  
Tumor Resection ◽  
Treatment Strategies ◽  
Molecular Data ◽  
Tumor Type ◽  
Small Bowel Adenocarcinoma ◽  
Single Center Experience ◽  
Best Response ◽  
Activating Mutation ◽  
Record Review

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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