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Døssing RH, Broman JJA, O'Rourke CJ, Tabaksblat EM, Andersen JB, Hansen CP, Poulsen TS, Høgdall EVS, Schou JHV, Høgdall D. Molecularly redefining small bowel adenocarcinoma to accelerate precision patient care - protocol of a multicenter observational cohort biomarker study. BMC Cancer 2025; 25:22. [PMID: 39773121 PMCID: PMC11707884 DOI: 10.1186/s12885-024-13369-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 12/19/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Small Bowel Adenocarcinoma (SBA) is a rare gastrointestinal cancer with a limited understanding of the molecular pathology. This study aims to bridge the knowledge gap, providing a robust molecular foundation for SBA and addressing the clinical challenges inherent in treating this orphan disease. The study proposes to redefine the clinical management for SBA patients through advanced molecular profiling techniques to improve potential precision medicine. METHODS/DESIGN This National multicenter, observational cohort study combines retrospective and prospective analyses across Danish University Hospitals. The study enrolls patients diagnosed with SBA, retrospectively from 2009 and prospectively from 2022 onwards. Molecular profiling, including DNA, RNA, and T-cell receptor sequencing, will be conducted on SBA tissue samples. The primary outcome is to categorize SBA into consensus molecular-guided subgroups. Secondary outcomes include correlating these subgroups with clinical features, treatment responses, and patient outcomes. Machine learning algorithms will be employed for bioinformatic analyses to interpret molecular data. Ethical approval has been obtained, and patient consent will be secured for the retrospective study component. DISCUSSION The molecular and clinical characterization of SBA is expected to add novel insights into the heterogeneity of this rare disease. By identifying molecular subgroups, the research could enable the development of personalized treatment strategies, a paradigm shift within SBA. The study acknowledges the challenges of working with orphan diseases, including limited patient numbers and diverse clinical presentations. However, its findings will have the potential to substantially impact future clinical practices and guide targeted therapies for SBA patients. TRIAL REGISTRATION ClinicalTrials.gov NCT06234306.
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Affiliation(s)
- Rasmus Haunstrup Døssing
- Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Borgmester Ib Juuls Vej 1, Herlev, 2730, Denmark.
| | - Julia Johanna Almer Broman
- Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Borgmester Ib Juuls Vej 1, Herlev, 2730, Denmark
| | - Colm J O'Rourke
- Department of Health and Medical Sciences, Biotech Research and Innovation Center, University of Copenhagen, Ole Maaløes Vej 5, 4th Floor, Copenhagen N, 2200, Denmark
| | | | - Jesper Bøje Andersen
- Department of Health and Medical Sciences, Biotech Research and Innovation Center, University of Copenhagen, Ole Maaløes Vej 5, 4th Floor, Copenhagen N, 2200, Denmark
| | - Carsten Palnæs Hansen
- Department Surgical Gastroenterology, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, Copenhagen Ø, 2100, Denmark
| | - Tim Svenstrup Poulsen
- Department of Pathology, Copenhagen University Hospital - Herlev and Gentofte, Borgmester Ib Juuls Velj 1, Herlev, 2730, Denmark
| | - Estrid V S Høgdall
- Department of Pathology, Copenhagen University Hospital - Herlev and Gentofte, Borgmester Ib Juuls Velj 1, Herlev, 2730, Denmark
| | - Jakob Hagen Vasehus Schou
- Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Borgmester Ib Juuls Vej 1, Herlev, 2730, Denmark
| | - Dan Høgdall
- Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Borgmester Ib Juuls Vej 1, Herlev, 2730, Denmark.
- Department of Health and Medical Sciences, Biotech Research and Innovation Center, University of Copenhagen, Ole Maaløes Vej 5, 4th Floor, Copenhagen N, 2200, Denmark.
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Aparicio T, Henriques J, Svrcek M, Zaanan A, Manfredi S, Casadei-Gardini A, Tougeron D, Gornet JM, Jary M, Terrebonne E, Piessen G, Afchain P, Lecaille C, Pocard M, Lecomte T, Rimini M, Di Fiore F, Le Brun Ly V, Cascinu S, Vernerey D, Laurent Puig P. Genomic profiling of small bowel adenocarcinoma: a pooled analysis from 3 databases. Br J Cancer 2024; 131:49-62. [PMID: 38745088 PMCID: PMC11231144 DOI: 10.1038/s41416-024-02687-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 04/04/2024] [Accepted: 04/08/2024] [Indexed: 05/16/2024] Open
Abstract
BACKGROUND Small bowel adenocarcinoma is a rare disease. The genomic profiling tumours according to clinical characteristics and its impact on the prognosis remains unclear. METHODS A pooled analysis of clinical data, genomic profiling and MisMatch Repair (MMR) status from three databases was performed. RESULTS A total of 188 tumour samples were analysed. A predisposing disease was reported in 22.3%, mainly Lynch syndrome and Crohn's disease. The tumours were localized in 80.2% and metastatic in 18.8%. The most frequent mutations were KRAS (42.0%) among them 7/79 are G12C, TP53 (40.4%), APC (19.1%), PIK3CA (18.6%), SMAD4 (12.8%) and ERBB2 (9.6%). Mutation distribution differed according to predisposing disease for TP53, ERBB2, IDH1, FGFR3, FGFR1 and KDR. KRAS and SMAD4 mutations were more frequent in metastatic tumour, whereas ERBB2 mutations were absent in metastatic tumour. For localized tumour, APC mutation was independently associated with a poor overall survival (OS) (p = 0.0254). 31.8% of localized tumours and 11.3% of metastatic tumours were dMMR (29.8% of the entire cohort). A dMMR status was associated with a better OS (HR = 0.61 [0.39-0.96], p = 0.0316). CONCLUSIONS There is a different genomic profile according to the stage and predisposing disease. dMMR and APC mutation in localized tumour predict a better prognosis.
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Affiliation(s)
- Thomas Aparicio
- Department of Gastroenterology and Digestive Oncology, Saint Louis Hospital, APHP, Université de Paris Cité, Paris, France.
| | - Julie Henriques
- Methodology and Quality of Life Unit in Oncology, CHU Besançon, Hôpital Jean Minjoz, Besançon, France
- Bourgogne Franche-Comté University, INSERM, Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France
| | - Magali Svrcek
- Sorbonne Université, Department of Pathology, Saint Antoine Hospital, APHP, Paris, France
| | - Aziz Zaanan
- Department of Gastroenterology and Digestive Oncology, Georges Pompidou Hospital, APHP, Université de Paris Cité, Paris, France
| | - Sylvain Manfredi
- Digestive Cancer Registry of Burgundy, INSERM, LNC UMR1231, University Bourgogne Franche-Comté, Dijon-Bourgogne University Hospital, Dijon, France
| | | | - David Tougeron
- Department of Hepato-Gastroenterology, CHU de Poitiers, Poitiers, France
| | - Jean-Marc Gornet
- Department of Gastroenterology and Digestive Oncology, Saint Louis Hospital, APHP, Université de Paris Cité, Paris, France
| | - Marine Jary
- Department of Digestive and Hepatobiliary Surgery, University Hospital of Clermont-Ferrand, U1071 INSERM, Clermont-Auvergne University, Clermont-Ferrand, France
| | - Eric Terrebonne
- Department of Gastroenterology, CHU Haut-Lévêque, Pessac, France
| | - Guillaume Piessen
- Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, University Lille, Lille, France
| | - Pauline Afchain
- Department of Oncology, Saint Antoine Hospital, APHP, Paris, France
| | - Cédric Lecaille
- Department of Gastroenterology, Polyclinic Bordeaux Nord, Bordeaux, France
| | - Marc Pocard
- Department of Digestive Surgery, Pitié-Salpétrière Hospital, APHP, Paris, France
| | - Thierry Lecomte
- Department of Hepato-Gastroenterology and Digestive Oncology, Trousseau Hospital, CHU Tours, Tours, France
| | - Margherita Rimini
- Department of Oncology, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy
| | - Frédéric Di Fiore
- Department of Digestive Oncology, CHU Charles Nicolle, Rouen, France
| | | | - Stefano Cascinu
- Department of Oncology, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy
| | - Dewi Vernerey
- Methodology and Quality of Life Unit in Oncology, CHU Besançon, Hôpital Jean Minjoz, Besançon, France
- Bourgogne Franche-Comté University, INSERM, Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France
| | - Pierre Laurent Puig
- Department of Biology, Georges Pompidou Hospital, APHP, Université de Paris Cité, Paris, France
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Li L, Zhang S, Fu G. Trending of small bowel adenocarcinoma research from 2000 to 2022: A bibliometric analysis. Medicine (Baltimore) 2024; 103:e37795. [PMID: 38608051 PMCID: PMC11018234 DOI: 10.1097/md.0000000000037795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Accepted: 03/14/2024] [Indexed: 04/14/2024] Open
Abstract
Small bowel adenocarcinoma (SBA) is a rare tumor entity with a relatively poor prognosis. Diagnosis and management of SBA are still challenging despite recent advancement of diagnostic methods and publication of guidelines. This study aimed to analyze and visualize the trending of SBA research in the past 22 years in the 21st century through bibliometric analysis. Our study collected 1270 publication records of SBA from 2000 Jan 1st to 2022 December 31 from Web of Science and used VOSviewer and CiteSpace to analyze countries, institutions, journals, authors, references and keywords to present the latest trends in SBA research. The USA was the most productive country in terms of the total number of publications (n = 418). The Mayo Clinic (n = 22) and University of Texas MD Cancer Center (n = 22) were the institutions with top publications. The "World Journal Of Gastroenterology" (n = 30) had the largest publications. Overman Michael J (n = 17) was the most active and prolific author. The "small bowel adenocarcinoma" was the most frequent keyword. Our bibliometric analysis provides a comprehensive overview of the trends and gaps in the research of SBA. Despite the challenges faced, researchers from USA, Japan and China have made significant contributions to the field of SBA research, and further research is necessary to develop evidence-based guidelines, and advance the understanding and management of SBA.
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Affiliation(s)
- Li Li
- The First Affiliated Hospital, Department of Gastrointestinal Surgery, Hengyang Medical School, University of South China, Hengyang, China
| | - Shao Zhang
- The First Affiliated Hospital, Department of Gastrointestinal Surgery, Hengyang Medical School, University of South China, Hengyang, China
| | - Guang Fu
- The First Affiliated Hospital, Department of Gastrointestinal Surgery, Hengyang Medical School, University of South China, Hengyang, China
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de Bakker JK, Meijer LL, Zonderhuis BM, van der Vliet HJ, Daams F, van Grieken NCT, Lissenberg-Witte BI, Kazemier G. Adjuvant chemotherapy for resected duodenal adenocarcinoma: a case-matched analysis in nation wide cohort. Acta Chir Belg 2023; 123:502-508. [PMID: 35727126 DOI: 10.1080/00015458.2022.2092961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Accepted: 06/17/2022] [Indexed: 11/01/2022]
Abstract
BACKGROUND Duodenal adenocarcinoma (DA) is a rare tumor for which survival data on adjuvant chemotherapy in patients after surgical treatment are unclear. This case-matched study in a nationwide cohort aims to investigate the benefit of adjuvant chemotherapy for patients with resectable DA on overall survival. METHODS All patients diagnosed with DA and intestinal type periampullary adenocarcinoma (PVA) in the Netherlands between 2000 and 2015 were included (n = 1316). Patients with disease stages II and III who underwent resection and adjuvant chemotherapy were matched (1:2), based on identified covariates associated with OS, with patients who underwent surgery alone. Overall survival was compared using Kaplan-Meier estimates. RESULTS The median OS was 49.9 months in patients who underwent curative resection (n = 649). Univariate and multivariate analysis showed a significant influence of age, lymph node involvement, and T- stage on survival. The group of patients receiving adjuvant treatment consisted of 43 patients and the non-adjuvant group of 83 case-matched patients. The median OS of the complete matched cohort (n = 126) was 26.9 months. No statistically significant survival benefit was found for the adjuvant group as compared to the group treated with surgery alone (median OS = 34.4 months and 23.0 months, p = 0.20). CONCLUSION This population-based, case-matched analysis demonstrates no statistically significant survival benefit for adjuvant chemotherapy after curative resection in stages II and III patients. Future studies with specified treatment regimens as well as thorough stratification for prognostic factors will be required in order to more definitively determine the role of adjuvant therapy.
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Affiliation(s)
- J K de Bakker
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands
| | - L L Meijer
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands
| | - B M Zonderhuis
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands
| | - H J van der Vliet
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands
| | - F Daams
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands
| | - N C T van Grieken
- Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands
| | - B I Lissenberg-Witte
- Department of Epidemiology and Biostatistics, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands
| | - G Kazemier
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands
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de Bakker J, Sommeijer D, Besselink M, Kazemier G, van Grieken N. The use of histopathological subtyping in patients with ampullary cancer: a nationwide analysis. World J Surg Oncol 2022; 20:406. [PMID: 36566267 PMCID: PMC9789567 DOI: 10.1186/s12957-022-02873-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Accepted: 12/08/2022] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Recent guidelines advise to subtype adenocarcinoma at the ampulla and papilla of Vater (here: ampullary cancer) as intestinal, pancreatobiliary, and mixed, because this has consequences for both prognosis and treatment. This nationwide study aimed to investigate how often histopathological subtyping is performed in daily clinical practice in patients with ampullary cancer. METHODS Pathology reports of all patients with ampullary cancer were retrieved from the Dutch nationwide pathology database (PALGA, 1991-2020). Reports were assessed for the presence and methods used for the classification of these tumors into intestinal, pancreatobiliary, and mixed subtypes. The use of immunohistochemical markers was recorded. RESULTS Overall, 5246 patients with ampullary cancer were included. In 1030 (19.6%) patients, a distinction between intestinal, pancreatobiliary, and mixed subtypes was made. Use of subtyping increased from 3% in 1991-1993 to 37% in 2018-2020. In 274 of the 1030 (26.6%) patients, immunohistochemistry was used to make this distinction. A gradual increase in the use of various immunohistochemical markers was seen over time since 2008, with cytokeratin 7, cytokeratin 20, and CDX2 being the most common. Staining of DPC4/SMAD4 was increasingly used since 2012. CONCLUSION Despite recent improvements in the use of subtyping in ampullary cancer, the distinction between intestinal, pancreatobiliary, and mixed subtypes is only made in a minority of patients. Nationwide efforts are required to standardize the pathological distinction of the various subtypes of ampullary cancer.
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Affiliation(s)
- Jacob de Bakker
- grid.12380.380000 0004 1754 9227Department of Surgery, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands ,grid.16872.3a0000 0004 0435 165XCancer Center Amsterdam, Amsterdam, The Netherlands
| | - Dirkje Sommeijer
- grid.16872.3a0000 0004 0435 165XCancer Center Amsterdam, Amsterdam, The Netherlands ,grid.7177.60000000084992262Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Marc Besselink
- grid.16872.3a0000 0004 0435 165XCancer Center Amsterdam, Amsterdam, The Netherlands ,grid.7177.60000000084992262Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Geert Kazemier
- grid.12380.380000 0004 1754 9227Department of Surgery, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands ,grid.16872.3a0000 0004 0435 165XCancer Center Amsterdam, Amsterdam, The Netherlands
| | - Nicole van Grieken
- grid.16872.3a0000 0004 0435 165XCancer Center Amsterdam, Amsterdam, The Netherlands ,grid.12380.380000 0004 1754 9227Department of Pathology, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands
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Single-cell profiling reveals molecular basis of malignant phenotypes and tumor microenvironments in small bowel adenocarcinomas. Cell Discov 2022; 8:92. [PMID: 36104333 PMCID: PMC9475032 DOI: 10.1038/s41421-022-00434-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 06/06/2022] [Indexed: 11/08/2022] Open
Abstract
AbstractSmall bowel adenocarcinomas (SBAs) are rare malignant tumors with a high mortality rate, and their molecular characteristics are still largely unexplored. Here we performed single-cell RNA sequencing for tumor samples from 12 SBA patients and predicted drug candidates for SBA. We identified four prevalent subtypes of malignant cells with distinct signatures including cell cycle program, mitochondria program, metabolism program and epithelial–mesenchymal transition (EMT) program. The progression relationships of these four subtypes of malignant cells were also revealed, which started from the cell cycle program, through the mitochondria program and then progressing into either the metabolism program or the EMT program. Importantly, ligand–receptor interaction pairs were found to be specifically enriched in pairs of EMT-program malignant cells and highly exhausted CD8+ T cells, suggesting that cancer cell subpopulations with EMT features may contribute most to the exhaustion of T cells. We also showed that the duodenal subtype of SBA exhibited molecular features more similar to gastric cancer whereas jejunal subtype of SBA more similar to colorectal cancer. Especially, we predicted specific drugs for SBA based on differential gene expression signatures between malignant cells and normal epithelial cells of SBA, and verified more potent inhibitory effects of volasertib and tozasertib for SBA cancer cells than conventional drugs of SBA at the same concentration, which provides new clues for treatments of SBA. In summary, our study provides a blueprint of the molecular signatures of both tumor cells and tumor microenvironment cells in SBA and reveals potential targets and drug candidates for its clinical treatments.
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Tatsuguchi A, Yamada T, Ueda K, Furuki H, Hoshimoto A, Nishimoto T, Omori J, Akimoto N, Gudis K, Tanaka S, Fujimori S, Shimizu A, Iwakiri K. Genetic analysis of Japanese patients with small bowel adenocarcinoma using next-generation sequencing. BMC Cancer 2022; 22:723. [PMID: 35778698 PMCID: PMC9250163 DOI: 10.1186/s12885-022-09824-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 06/23/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Small bowel adenocarcinomas (SBAs) are rare and there is little comprehensive data on SBA genomic alterations for Asian patients. This study aimed to profile genomic alterations of SBA in Japanese patients using targeted next-generation sequencing (NGS). METHODS We examined 22 surgical resections from patients with primary SBA. SBA genomic alterations were analyzed by NGS. Mismatch repair (MMR) status was determined by immunohistochemical analysis. Mucin phenotypes were classified as gastric (G), intestinal (I), gastrointestinal (GI), and null (N) types on MUC2, MUC5AC, MUC6, and CD10 immunostaining. RESULTS The most common genomic alterations found in SBA tumors were TP53 (n = 16), followed by KRAS (n = 6), APC (n = 5), PIK3CA (n = 4), CTNNB1 (n = 3), KIT (n = 2), BRAF (n = 2), CDKN2A (n = 2), and PTEN (n = 2). Deficient MMR tumors were observed in 6 out of 22 patients. Tumor mucin phenotypes included 2 in G-type, 12 in I-type, 3 in GI-type, and 5 in N-type. APC and CTNNB1 mutations were not found in G-type and GI-type tumors. KRAS mutations were found in all tumor types except for G-type tumors. TP53 mutations were found in all tumor types. Although no single gene mutation was associated with overall survival (OS), we found that KRAS mutations were associated with significant worse OS in patients with proficient MMR tumors. CONCLUSIONS SBA genomic alterations in Japanese patients do not differ significantly from those reports in Western countries. Tumor localization, mucin phenotype, and MMR status all appear to impact SBA gene mutations.
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Affiliation(s)
- Atsushi Tatsuguchi
- Department of Gastroenterology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603 Japan
- Department of Analytic Human Pathology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8602 Japan
| | - Takeshi Yamada
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603 Japan
| | - Koji Ueda
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603 Japan
| | - Hiroyasu Furuki
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603 Japan
| | - Aitoshi Hoshimoto
- Department of Gastroenterology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603 Japan
| | - Takayoshi Nishimoto
- Department of Gastroenterology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603 Japan
| | - Jun Omori
- Department of Gastroenterology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603 Japan
| | - Naohiko Akimoto
- Department of Gastroenterology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603 Japan
| | - Katya Gudis
- Department of Gastroenterology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603 Japan
| | - Shu Tanaka
- Department of Gastroenterology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603 Japan
| | - Shunji Fujimori
- Department of Gastroenterology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603 Japan
| | - Akira Shimizu
- Department of Analytic Human Pathology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8602 Japan
| | - Katsuhiko Iwakiri
- Department of Gastroenterology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603 Japan
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Molecular Landscape of Small Bowel Adenocarcinoma. Cancers (Basel) 2022; 14:cancers14051287. [PMID: 35267592 PMCID: PMC8909755 DOI: 10.3390/cancers14051287] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 02/23/2022] [Accepted: 02/28/2022] [Indexed: 12/13/2022] Open
Abstract
Small bowel adenocarcinoma (SBA) is a rare malignancy, with lower incidence, later stage at diagnosis, and poor overall prognosis compared to other cancers of the gastrointestinal tract. Owing to the rarity of the disease along with the paucity of high-quality tissue samples and preclinical models, little is known about the molecular alterations characteristic of SBA. This is reflected by the fact that the clinical management of SBA is primarily extrapolated from colorectal cancer (CRC). Recent advances in genomic profiling have highlighted key differences between these tumors, establishing SBA as a molecularly unique intestinal cancer. Moreover, comprehensive molecular analysis has identified a relatively high incidence of potentially targetable genomic alterations in SBA, predictive of response to targeted and immunotherapies. Further advances in our knowledge of the mutational and transcriptomic landscape of SBA, guided by an increased understanding of the molecular drivers of SBA, will provide opportunities to develop novel diagnostic tools and personalized therapeutic strategies.
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Gelsomino F, Balsano R, De Lorenzo S, Garajová I. Small Bowel Adenocarcinoma: From Molecular Insights to Clinical Management. Curr Oncol 2022; 29:1223-1236. [PMID: 35200603 PMCID: PMC8870676 DOI: 10.3390/curroncol29020104] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 02/10/2022] [Accepted: 02/14/2022] [Indexed: 12/03/2022] Open
Abstract
Small bowel adenocarcinoma (SBA) is a rare malignancy, with a rising incidence in recent decades, and accounts for roughly 40% of all cancers of the small bowel. The majority of SBAs arise in the duodenum and are associated with a dismal prognosis. Surgery remains the mainstay of treatment for localized disease, while systemic treatments parallel those used in colorectal cancer (CRC), both in the adjuvant and palliative setting. In fact, owing to the lack of prospective data supporting its optimal management, SBA has historically been treated in the same way as CRC. However, recent genetic and molecular data suggest a distinct profile from other gastrointestinal malignancies and support a more nuanced approach to its management. Herein, we briefly review the state-of-the-art in the clinical management of early-stage and advanced disease and recent discoveries of potentially actionable genetic alterations or pathways along with the most promising ongoing clinical trials, which will hopefully revolutionize the treatment landscape of this orphan disease in the foreseeable future.
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Affiliation(s)
- Fabio Gelsomino
- Department of Oncology and Hematology, Division of Oncology, University Hospital of Modena, 41124 Modena, Italy
| | - Rita Balsano
- Medical Oncology Unit, University Hospital of Parma, 43126 Parma, Italy; (R.B.); (I.G.)
| | | | - Ingrid Garajová
- Medical Oncology Unit, University Hospital of Parma, 43126 Parma, Italy; (R.B.); (I.G.)
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Khosla D, Dey T, Madan R, Gupta R, Goyal S, Kumar N, Kapoor R. Small bowel adenocarcinoma: An overview. World J Gastrointest Oncol 2022; 14:413-422. [PMID: 35317322 PMCID: PMC8918997 DOI: 10.4251/wjgo.v14.i2.413] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 08/09/2021] [Accepted: 01/22/2022] [Indexed: 02/06/2023] Open
Abstract
Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract. However, these tumors are among those with worst prognosis. Vague clinical signs and symptoms and radiological diagnostic challenges often delay treatment, which negatively impacts the prognosis of the patients. However, recent advances in imaging technology, like multidetector computed tomography, magnetic resonance imaging, and capsule endoscopy, have made earlier and accurate diagnosis possible. Surgery is the treatment of choice followed by adjuvant therapy. However, there are no strict treatment guidelines available for the management of SBA. Most of the available evidence from colorectal and gastric carcinoma has been extrapolated to adequately manage SBA. Prognosis for SBA is better than gastric carcinoma but worse than colorectal carcinoma. Currently, there is not enough information on the molecular characteristics and tumor pathogenesis. Because the incidence of SBA is very low, there is a need for further studies to evaluate the possible application of newer investigative agents and strategies to obtain a better outcome within the framework of international collaborations.
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Affiliation(s)
- Divya Khosla
- Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Treshita Dey
- Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Renu Madan
- Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Rahul Gupta
- Department of Gastroenterology, Shalby Multispeciality Hospital, Mohali 160062, Punjab, India
| | - Shikha Goyal
- Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Narendra Kumar
- Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Rakesh Kapoor
- Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
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11
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Sun H, Liu Y, Lv L, Li J, Liao X, Gong W. Prognostic Factors and Clinical Characteristics of Duodenal Adenocarcinoma With Survival: A Retrospective Study. Front Oncol 2022; 11:795891. [PMID: 34976838 PMCID: PMC8715708 DOI: 10.3389/fonc.2021.795891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 11/16/2021] [Indexed: 12/03/2022] Open
Abstract
Background To evaluate the clinical risk factors that influence the overall survival in patients with duodenal adenocarcinoma (DA) after tumor resection. Methods This study retrospectively analyzed 188 patients who underwent tumor resection for DA between January 2005 and June 2020 at Xiangyang Central Hospital. Results The median survival of the patients who underwent resectional operation was 54 months, longer than of those who underwent palliative surgery (20.8 months) (2,916.17; 95% CI, 916.3−9,280.5; p < 0.001). Survival of non-ampullary duodenal carcinoma patients (50.3 months; 95% CI, 39.7−61.8) was similar to that of ampullary duodenal carcinoma patients (59.3 months; 95% CI, 38.6−66.7) but was significantly better than that of papillary adenocarcinoma patients (38.9 months; 95% CI, 29.8−54.8; p = 0.386). Those with intestinal-type ductal adenocarcinomas had a longer median overall survival than those with the gastric type (61.8 vs. 46.7 months; p < 0.01) or pancreatic type (32.2 months; p < 0.001). Clinical DA samples had significantly diverse expressions of ATG12, IRS2, and IGF2. Higher expressions of the ATG12 and IRS2 proteins were significantly correlated with worse survival. Multivariate Cox regression analysis revealed that lymph node metastasis (hazard ratio (HR), 6.44; 95% CI, 3.68−11.27; p < 0.0001), margin status (HR, 4.94; 95% CI, 2.85−8.54; p < 0.0001), and high expression of ATG12 (HR, 1.89; 95% CI, 1.17−3.06; p = 0.0099) were independent prognostic factors negatively associated with survival in patients undergoing curative resection. There was no survival difference between the groups with ampullary, non-ampullary, and papillary adenocarcinomas treated with adjuvant chemotherapy (p = 0.973). Conclusion Gastric/pancreatic type, high expression of ATG12, lymph node metastases, and margin status were negative prognosticators of survival in patients with DAs than in those with tumor anatomical location. Curative resection is the best treatment option for appropriate patients.
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Affiliation(s)
- Huapeng Sun
- Department of General Surgery, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, China
| | - Yi Liu
- Department of Medicinal Chemistry, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
| | - Long Lv
- Department of General Surgery, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, China
| | - Jingwen Li
- Department of Oncology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, China
| | - Xiaofeng Liao
- Department of General Surgery, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, China
| | - Wei Gong
- Department of Oncology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, China
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12
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Dong Z, Xia X, Zhang Z. Systemic Therapy for Microsatellite Instability Small Bowel Adenocarcinoma With Mesenteric Vascular Embolism as Initial Symptom: A Case Report. Front Med (Lausanne) 2021; 8:764233. [PMID: 34820399 PMCID: PMC8606888 DOI: 10.3389/fmed.2021.764233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 10/19/2021] [Indexed: 11/26/2022] Open
Abstract
Background: Small bowel adenocarcinoma are relatively rare tumors of the digestive system. Due to the lack of specific screening methods, patients are often diagnosed at an advanced stage. At present, there is no specific surgical guidance and chemotherapy regimen for small bowel adenocarcinoma. Here, we report a rare small bowel adenocarcinoma case with mesenteric vascular embolization and microsatellite instability, in which palliative surgery combined with chemotherapy and anti-Programmed cell death protein 1(PD-1) therapy resulted in complete remission. Case Presentation: The patient was a 55-year-old man who was admitted for suspected small bowel adenocarcinoma combined with incomplete ileus, mesenteric vascular occlusion and distant metastasis. We performed palliative surgery to remove adenocarcinoma as well as relieve obstruction. Then according to the pathological and immunohistochemical results (Stage IV and microsatellite instability), we used XELOX regimen combined with anti-PD-1 therapy. In last 2 years follow up, this patient achieved complete remission. Conclusions: The possibility of small intestinal tumor should be considered in patients with mesenteric vascular obstruction. PD-1 blockade is an effective therapy for small bowel adenocarcinoma with microsatellite instability.
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Affiliation(s)
| | | | - Zizhen Zhang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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13
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Aparicio T, Svrcek M, Henriques J, Afchain P, Lièvre A, Tougeron D, Gagniere J, Terrebonne E, Piessen G, Legoux JL, Lecaille C, Pocard M, Gornet JM, Zaanan A, Lavau-Denes S, Lecomte T, Deutsch D, Vernerey D, Puig PL. Panel gene profiling of small bowel adenocarcinoma: Results from the NADEGE prospective cohort. Int J Cancer 2021; 148:1731-1742. [PMID: 33186471 DOI: 10.1002/ijc.33392] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 10/27/2020] [Accepted: 10/29/2020] [Indexed: 12/20/2022]
Abstract
Small bowel adenocarcinoma (SBA) is a rare tumour. Large genomic analyses with prognostic assessments are lacking. The NADEGE cohort has enrolled 347 patients with all stage SBA from 2009 to 2012. Next-generation sequencing investigates the presence of 740 hotspot somatic mutations in a panel of 46 genes involved in carcinogenesis. The mismatch repair (MMR) status was assessed by immunochemistry. We have collected 196 tumour samples and 125 had conclusive results for mutation analysis. The number of mutations was 0 in 9.6% of tumours, only 1 in 32.0%, 2 in 26.4% and ≥3 in 32.0%. Overall, at least one genomic alteration was observed in 90.4% of tumour. The most frequent genomic alteration was in KRAS (44.0%), TP53 (38.4%), PIK3CA (20.0%), APC (18.4%), SMAD4 (14.4%) and ERBB2 (7.2%) genes. KRAS mutations were more frequent in synchronous metastatic tumours than in localised tumours (72.7% vs 38.2%, P = .003). There was no significant difference in the mutation rates according to primary location for the most frequently altered gene. ATM, FGFR3 and FGFR1 gene alterations were associated with Lynch syndrome and IDH1 mutations with Crohn disease. dMMR tumours were associated with younger age, localised tumours, less KRAS but more SMARCB1 mutations. No genomic alteration was associated with overall survival. There is a trend for better survival in patient with dMMR tumours. In conclusion, there is a different genomic alteration profile in SBA according to predisposing diseases. No association between genomic alterations and prognoses was observed except for a trend of better prognoses associated with dMMR.
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Affiliation(s)
- Thomas Aparicio
- Department of Gastroenterology and Digestive Oncology, Saint Louis Hospital, APHP, Université de Paris, Paris, France
| | - Magali Svrcek
- Sorbonne Université, Department of Pathology, Saint Antoine Hospital, Paris, France
| | - Julie Henriques
- Methodology and Quality of Life Unit in Oncology, EA 3181, University Hospital, Besançon, France
- Bourgogne Franche-Comté University, INSERM, Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France
| | - Pauline Afchain
- Department of Oncology, Saint Antoine Hospital, Paris, France
| | - Astrid Lièvre
- Department of Gastroenterology, Pontchaillou Hospital, Rennes 1 University; INSERM U1242, Rennes, France
| | - David Tougeron
- Department of Hepato-Gastroenterology, CHU de Poitiers, Poitiers, France
| | - Johan Gagniere
- Department of Digestive and Hepatobiliary Surgery, University Hospital of Clermont-Ferrand, U1071 INSERM, Clermont-Auvergne University, Clermont-Ferrand, France
| | - Eric Terrebonne
- Department of Gastroenterology, CHU Haut-Lévêque, Pessac, France
| | - Guillaume Piessen
- Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, University Lille, Lille, France
| | - Jean-Louis Legoux
- Department of Hepato-Gastroenterology and Digestive Oncology, CHR La Source, Orléans, France
| | - Cédric Lecaille
- Department of Gastroenterology, Polyclinic Bordeaux Nord, Bordeaux, France
| | - Marc Pocard
- Department of Digestive Surgery, Lariboisière Hospital, Paris, France
| | - Jean-Marc Gornet
- Department of Gastroenterology and Digestive Oncology, Saint Louis Hospital, APHP, Université de Paris, Paris, France
| | - Aziz Zaanan
- Department of Gastroenterology and Digestive Oncology, Georges Pompidou Hospital, APHP, Université de Paris, Paris, France
| | | | - Thierry Lecomte
- Department of Hepato-Gastroenterology and Digestive Oncology, Trousseau Hospital, Tours, France
| | - David Deutsch
- Department of Gastroenterology, Avicenne Hospital, Bobigny, France
| | - Dewi Vernerey
- Methodology and Quality of Life Unit in Oncology, EA 3181, University Hospital, Besançon, France
- Bourgogne Franche-Comté University, INSERM, Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France
| | - Pierre Laurent Puig
- Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, Paris, France
- Department of Biology, Georges Pompidou Hospital, APHP, Université de Paris, Paris, France
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14
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Ota R, Sawada T, Tsuyama S, Sasaki Y, Suzuki H, Kaizaki Y, Hasatani K, Yamamoto E, Nakanishi H, Inagaki S, Tsuji S, Yoshida N, Doyama H, Minato H, Nakamura K, Kasashima S, Kubota E, Kataoka H, Tokino T, Yao T, Minamoto T. Integrated genetic and epigenetic analysis of cancer-related genes in non-ampullary duodenal adenomas and intramucosal adenocarcinomas. J Pathol 2020; 252:330-342. [PMID: 32770675 PMCID: PMC7693035 DOI: 10.1002/path.5529] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 07/20/2020] [Accepted: 07/28/2020] [Indexed: 12/24/2022]
Abstract
The molecular and clinical characteristics of non‐ampullary duodenal adenomas and intramucosal adenocarcinomas are not fully understood because they are rare. To clarify these characteristics, we performed genetic and epigenetic analysis of cancer‐related genes in these lesions. One hundred and seven non‐ampullary duodenal adenomas and intramucosal adenocarcinomas, including 100 small intestinal‐type tumors (90 adenomas and 10 intramucosal adenocarcinomas) and 7 gastric‐type tumors (2 pyloric gland adenomas and 5 intramucosal adenocarcinomas), were investigated. Using bisulfite pyrosequencing, we assessed the methylation status of CpG island methylator phenotype (CIMP) markers and MLH1. Then using next‐generation sequencing, we performed targeted exome sequence analysis within 75 cancer‐related genes in 102 lesions. There were significant differences in the clinicopathological and molecular variables between small intestinal‐ and gastric‐type tumors, which suggests the presence of at least two separate carcinogenic pathways in non‐ampullary duodenal adenocarcinomas. The prevalence of CIMP‐positive lesions was higher in intramucosal adenocarcinomas than in adenomas. Thus, concurrent hypermethylation of multiple CpG islands is likely associated with development of non‐ampullary duodenal intramucosal adenocarcinomas. Mutation analysis showed that APC was the most frequently mutated gene in these lesions (56/102; 55%), followed by KRAS (13/102; 13%), LRP1B (10/102; 10%), GNAS (8/102; 8%), ERBB3 (7/102; 7%), and RNF43 (6/102; 6%). Additionally, the high prevalence of diffuse or focal nuclear β‐catenin accumulation (87/102; 85%) as well as mutations of WNT pathway components (60/102; 59%) indicates the importance of WNT signaling to the initiation of duodenal adenomas. The higher than previously reported frequency of APC gene mutations in small bowel adenocarcinomas as well as the difference in the APC mutation distributions between small intestinal‐type adenomas and intramucosal adenocarcinomas may indicate that the adenoma–carcinoma sequence has only limited involvement in duodenal carcinogenesis. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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Affiliation(s)
- Ryosuke Ota
- Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
| | - Takeshi Sawada
- Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.,Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Sho Tsuyama
- Department of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Yasushi Sasaki
- Division of Biology, Department of Liberal Arts and Sciences, Center for Medical Education, Sapporo Medical University, Sapporo, Japan
| | - Hiromu Suzuki
- Department of Molecular Biology, Sapporo Medical University, Sapporo, Japan
| | - Yasuharu Kaizaki
- Department of Pathology, Fukui Prefectural Hospital, Fukui, Japan
| | - Kenkei Hasatani
- Department of Gastroenterology, Fukui Prefectural Hospital, Fukui, Japan
| | - Eiichiro Yamamoto
- Department of Molecular Biology, Sapporo Medical University, Sapporo, Japan
| | - Hiroyoshi Nakanishi
- Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
| | - Satoko Inagaki
- Department of Advanced Research in Community Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
| | - Shigetsugu Tsuji
- Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Kanazawa, Japan
| | - Naohiro Yoshida
- Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Kanazawa, Japan
| | - Hisashi Doyama
- Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Kanazawa, Japan
| | - Hiroshi Minato
- Department of Pathology, Ishikawa Prefectural Central Hospital, Kanazawa, Japan
| | - Keishi Nakamura
- Department of Gastroenterological Surgery, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Satomi Kasashima
- Department of Clinical Laboratory Science, Kanazawa University, Kanazawa, Japan
| | - Eiji Kubota
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Hiromi Kataoka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takashi Tokino
- Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan
| | - Takashi Yao
- Department of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Toshinari Minamoto
- Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
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15
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Meijer LL, Strijker M, de Bakker JK, Toennaer JGJ, Zonderhuis BM, van der Vliet HJ, Wilmink H, Verheij J, Daams F, Busch OR, van Grieken NCT, Besselink MG, Kazemier G. Clinical outcomes of patients with duodenal adenocarcinoma and intestinal-type papilla of Vater adenocarcinoma. World J Gastrointest Oncol 2020; 12:347-357. [PMID: 32206184 PMCID: PMC7081109 DOI: 10.4251/wjgo.v12.i3.347] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 01/04/2020] [Accepted: 01/20/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Duodenal adenocarcinoma (DA) and intestinal-type papilla of Vater adenocarcinoma (it-PVA) are rare malignancies of the gastrointestinal tract. Current therapeutic options are translated nowadays from treatment strategies for patients with colorectal cancer due to histopathological similarities.
AIM To retrospectively investigate the clinical outcome of patients with DA and it-PVA.
METHODS All patients with DA and it-PVA diagnosed between 2000 and 2017 were included at two academic centers in the Netherlands. All patients with histopathologically-confirmed DA or it-PVA were eligible for inclusion. Clinical outcome was compared between DA and it-PVA per disease stage. In the subgroup of stage IV disease, survival after local treatment of oligometastases was compared with systemic therapy or supportive care.
RESULTS In total, 155 patients with DA and it-PVA were included. Patients with it-PVA more often presented with stage I disease, while DA was more often diagnosed at stage IV (P < 0.001). Of all patients, 79% were treated with curative intent. The median survival was 39 mo, and no difference in survival was found for patients with DA and it-PVA after stratification for disease stage. Seven (23%) of 31 patients with synchronous stage IV disease underwent resection of the primary tumor, combined with local treatment of oligometastases. Local treatment of metastases was associated with an overall survival of 37 mo, compared to 14 and 6 mo for systemic therapy and supportive care, respectively.
CONCLUSION Survival of patients with DA and it-PVA is comparable per disease stage. These results suggest a potential benefit for local treatment strategies in selected patients with oligometastases, although additional prospective studies are needed.
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Affiliation(s)
- Laura L Meijer
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, Noord-Holland 1081HV, The Netherlands
| | - Marin Strijker
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, Noord-Holland 1105AZ, The Netherlands
| | - Jacob K de Bakker
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, Noord-Holland 1081HV, The Netherlands
| | - Jurgen GJ Toennaer
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, Noord-Holland 1081HV, The Netherlands
| | - Barbara M Zonderhuis
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, Noord-Holland 1081HV, The Netherlands
| | - Hans J van der Vliet
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, Noord-Holland 1081HV, The Netherlands
| | - Hanneke Wilmink
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam Amsterdam, Noord-Holland 1105AZ, The Netherlands
| | - Joanne Verheij
- Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam Amsterdam, Noord-Holland 1105AZ, The Netherlands
| | - Freek Daams
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, Noord-Holland 1081HV, The Netherlands
| | - Olivier R Busch
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, Noord-Holland 1105AZ, The Netherlands
| | - Nicole CT van Grieken
- Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam Noord-Holland 1081HV, The Netherlands
| | - Marc G Besselink
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, Noord-Holland 1105AZ, The Netherlands
| | - Geert Kazemier
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, Noord-Holland 1081HV, The Netherlands
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16
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Yasuda S, Harada S, Tsujimoto A, Aoki S, Takei T, Migita K, Ueno M, Tatsumi M, Watanabe A. A pathological complete response by chemotherapy with S-1 and oxaliplatin for a locally advanced duodenal adenocarcinoma in Lynch syndrome: a case report. Surg Case Rep 2019; 5:146. [PMID: 31637551 PMCID: PMC6803604 DOI: 10.1186/s40792-019-0712-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 09/27/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Although primary duodenal adenocarcinoma (DA) is a rare malignancy representing ~ 0.5% of all gastrointestinal cancers, the incidence of DA is more frequent in Lynch syndrome. Because of its rarity, treatment strategies or optimal chemotherapeutic regimens have not been clearly defined for advanced DA. CASE PRESENTATION A 72-year-old woman with Lynch syndrome visited our hospital with a right upper abdominal pain. Computed tomography (CT) showed wall thickness with enhancement in the second portion of the duodenum and adjacent abdominal wall, which suggested direct tumor invasion to the abdominal wall. Upper gastrointestinal endoscopy (UGE) showed a large ulcerative tumor in the second portion of the duodenum, and histological analysis revealed a poorly differentiated adenocarcinoma. A cT4N0M0, cStage IIB (Union for International Control Cancer TNM staging) DA was diagnosed. After three courses of chemotherapy with S-1 and oxaliplatin (SOX), follow-up CT and UGE showed shrinkage of the duodenal tumor. Therefore, the patient underwent pancreaticoduodenectomy with lymph node dissection with curative intent. Histological examination showed a pathological complete response to SOX therapy. The postoperative course was uneventful, and the patient was discharged on postoperative day 29. The patient received no adjuvant chemotherapy, and there has been no evidence of recurrence 6 months after the operation. CONCLUSIONS SOX therapy provided a remarkable response and can be an optimal chemotherapeutic regimen for advanced DA in Lynch syndrome.
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Affiliation(s)
- Satoshi Yasuda
- Department of Surgery, Nara Prefecture Western Medical Center, 1-14-16 Mimuro Sango-cho, Ikoma-gun, Nara, 636-0802, Japan.
| | - Suzuka Harada
- Department of Surgery, Nara Prefecture Western Medical Center, 1-14-16 Mimuro Sango-cho, Ikoma-gun, Nara, 636-0802, Japan
| | - Akinori Tsujimoto
- Department of Surgery, Nara Prefecture Western Medical Center, 1-14-16 Mimuro Sango-cho, Ikoma-gun, Nara, 636-0802, Japan
| | - Satoko Aoki
- Department of Surgery, Nara Prefecture Western Medical Center, 1-14-16 Mimuro Sango-cho, Ikoma-gun, Nara, 636-0802, Japan
| | - Takeshi Takei
- Department of Surgery, Nara Prefecture Western Medical Center, 1-14-16 Mimuro Sango-cho, Ikoma-gun, Nara, 636-0802, Japan
| | - Kazuhiro Migita
- Department of Surgery, Nara Prefecture Western Medical Center, 1-14-16 Mimuro Sango-cho, Ikoma-gun, Nara, 636-0802, Japan
| | - Masato Ueno
- Department of Surgery, Nara Prefecture Western Medical Center, 1-14-16 Mimuro Sango-cho, Ikoma-gun, Nara, 636-0802, Japan
| | - Mitsutoshi Tatsumi
- Department of Surgery, Nara Prefecture Western Medical Center, 1-14-16 Mimuro Sango-cho, Ikoma-gun, Nara, 636-0802, Japan
| | - Akihiko Watanabe
- Department of Surgery, Nara Prefecture Western Medical Center, 1-14-16 Mimuro Sango-cho, Ikoma-gun, Nara, 636-0802, Japan
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17
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Hirashita T, Ohta M, Tada K, Saga K, Takayama H, Endo Y, Uchida H, Iwashita Y, Inomata M. Prognostic factors of non-ampullary duodenal adenocarcinoma. Jpn J Clin Oncol 2018; 48:743-747. [PMID: 29931295 DOI: 10.1093/jjco/hyy086] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Accepted: 05/23/2018] [Indexed: 12/14/2022] Open
Abstract
Background Non-ampullary duodenal adenocarcinoma, excluding carcinoma in the ampulla of Vater, is a rare disease. Although several prognostic factors have been reported, they remain controversial due to the rarity of non-ampullary duodenal adenocarcinoma. The aims of this study were to investigate prognostic factors in patients with non-ampullary duodenal adenocarcinoma and to assess chemotherapy in patients with recurrence. Patients and methods Records of 25 patients who underwent surgical treatment for non-ampullary duodenal adenocarcinoma from 2004 to 2016 were retrospectively reviewed. The relationship between the clinicopathological factors and outcomes was investigated. Results Serum level of CA19-9, gross appearance, tumor size, tumor invasion, lymph node metastases, TNM stage and lymphatic and vascular invasion were significant risk factors of recurrence. Patients with recurrence who received chemotherapy according to regimens used to treat colorectal cancer had a better prognosis than those without chemotherapy (P = 0.016). Conclusion Advanced non-ampullary duodenal adenocarcinoma has a poor prognosis, but chemotherapy possibly improves the prognosis in the patients with recurrent non-ampullary duodenal adenocarcinoma.
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Affiliation(s)
- Teijiro Hirashita
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Yufu, Oita, Japan
| | - Masayuki Ohta
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Yufu, Oita, Japan
| | - Kazuhiro Tada
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Yufu, Oita, Japan
| | - Kunihiro Saga
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Yufu, Oita, Japan
| | - Hiroomi Takayama
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Yufu, Oita, Japan
| | - Yuichi Endo
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Yufu, Oita, Japan
| | - Hiroki Uchida
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Yufu, Oita, Japan
| | - Yukio Iwashita
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Yufu, Oita, Japan
| | - Masafumi Inomata
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Yufu, Oita, Japan
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18
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Meijer LL, Alberga AJ, de Bakker JK, van der Vliet HJ, Le Large TYS, van Grieken NCT, de Vries R, Daams F, Zonderhuis BM, Kazemier G. Outcomes and Treatment Options for Duodenal Adenocarcinoma: A Systematic Review and Meta-Analysis. Ann Surg Oncol 2018; 25:2681-2692. [PMID: 29946997 PMCID: PMC6097725 DOI: 10.1245/s10434-018-6567-6] [Citation(s) in RCA: 75] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Indexed: 12/18/2022]
Abstract
Background Duodenal adenocarcinoma (DA) is a rare tumor for which survival data per treatment modality and disease stage are unclear. This systematic review and meta-analysis aims to summarize the current literature on patient outcome after surgical, (neo)adjuvant, and palliative treatment in patients with DA. Methods A systematic search was performed according to the preferred reporting items for systematic reviews and meta-analyses guidelines, to 25 April 2017. Primary outcome was overall survival (OS), specified for treatment strategy or disease stage. Random-effects models were used for the calculation of pooled odds ratios per treatment modality. Included papers were also screened for prognostic factors. Results A total of 26 observational studies, comprising 6438 patients with DA, were included. Of these, resection with curative intent was performed in 71% (range 53–100%) of patients, and 29% received palliative treatment (range 0–61%). The pooled 5-year OS rate was 46% after curative resection, compared with 1% in palliative-treated patients (OR 0.04, 95% confidence interval [CI] 0.02–0.09, p < 0.0001). Both segmental resection and pancreaticoduodenectomy allowed adequate assessment of lymph node involvement and resulted in similar OS. Lymph node involvement correlated with worse OS (pooled 5-year survival rate 21% for nodal metastases vs. 65% for node-negative disease; OR 0.17, 95% CI 0.11–0.27, p < 0.0001). In the current literature, no survival benefit for adjuvant therapy after curative resection was found. Conclusion Resection with curative intent, either pancreaticoduodenectomy or segmental resection, and lack of nodal metastases, favors survival for DA. Further studies exploring multimodality (neo)adjuvant therapy are warranted to investigate their benefit. Electronic supplementary material The online version of this article (10.1245/s10434-018-6567-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Laura L Meijer
- Department of Surgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
| | - Anna J Alberga
- Department of Surgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
| | - Jacob K de Bakker
- Department of Surgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
| | - Hans J van der Vliet
- Department of Medical Oncology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
| | - Tessa Y S Le Large
- Department of Surgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.,Department of Medical Oncology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.,Laboratory for Experimental Oncology and Radiobiology, Academic Medical Center, Amsterdam, The Netherlands
| | - Nicole C T van Grieken
- Department of Pathology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
| | - Ralph de Vries
- Medical Library, VU University Amsterdam, Amsterdam, The Netherlands
| | - Freek Daams
- Department of Surgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
| | - Barbara M Zonderhuis
- Department of Surgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
| | - Geert Kazemier
- Department of Surgery, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
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Wu S, Chen JN, Zhang QW, Tang CT, Zhang XT, Tang MY, Li XB, Ge ZZ. A New Metastatic Lymph Node Classification-based Survival Predicting Model in Patients With Small Bowel Adenocarcinoma: A Derivation and Validation Study. EBioMedicine 2018; 32:134-141. [PMID: 29908920 PMCID: PMC6021266 DOI: 10.1016/j.ebiom.2018.05.022] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2018] [Revised: 04/23/2018] [Accepted: 05/17/2018] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Current methods of lymph node (LN) staging are controversial in predicting the survival of SBA. We aimed to develop an alternative LN-classification-based nomogram to individualize SBA prognosis. METHODS Based on the data from the Surveillance, Epidemiology, and End Results (SEER) database of patients diagnosed with SBA between 2004 and 2014, we identified the cut-off points for the number of LNs examined and the number found to be metastatic using the K-adaptive partitioning (KAPS) algorithm. Using metastatic LNs, a nomogram predicting the survival of SBA was derived, internally and externally validated, and measured by calibration curve, C-index, and decision curve analysis (DCA), and compared to the 8th TNM stage. RESULTS A total of 1516 patients were included. The cut-off of 17 was the optimal examined LN number. For metastatic LN numbers, the cut-off points were 0, 2, and 8. The C-index for the nomogram was higher than the 8th TNM staging (internal: 0.734; 95% CI, 0.693 to 0.775 vs. 0.677; 95% CI, 0.652 to 0.702, P < 0.001; external: 0.715; 95% CI, 0.674 to 0.756 vs. 0.648; 95% CI, 0.602 to 0.693, P < 0.001). Also, the nomogram showed good calibration in internal and external validation and larger net benefit than TNM staging. CONCLUSION We modified current N staging into a 4-level staging system based on the number of metastatic LNs: N0, no LN metastasis; N1, 1-2 metastatic LNs; N2, 3-8 metastatic LNs, and N3, >8 metastatic LNs and set the least examined LN number to 17. A nomogram based on this staging showed great clinical usability than TNM staging for predicting the survival of SBA patients.
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Affiliation(s)
- Shan Wu
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Jin-Nan Chen
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Qing-Wei Zhang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Chao-Tao Tang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Xin-Tian Zhang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Ming-Yu Tang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Xiao-Bo Li
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
| | - Zhi-Zheng Ge
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
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20
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de Bree E, Rovers KP, Stamatiou D, Souglakos J, Michelakis D, de Hingh IH. The evolving management of small bowel adenocarcinoma. Acta Oncol 2018; 57:712-722. [PMID: 29381126 DOI: 10.1080/0284186x.2018.1433321] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Accepted: 01/22/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Small bowel adenocarcinoma (SBA) is rare despite the fact that the small bowel represents the longest part and has the largest surface of all alimentary tract sections. Its incidence is 50-fold lower than that of colorectal carcinoma. It is often diagnosed at an advanced stage due to atypical and late symptoms, its low index of suspicion, difficult endoscopic access and poor detection by radiological imaging, resulting in impaired outcome. Due to its rarity and being molecularly a unique intestinal cancer, data regarding its optimal management are relatively sparse. MATERIAL AND METHODS A PubMed search was performed to identify relevant manuscripts that were recently published. Emerging data regarding the pathogenesis, the diagnosis and the treatment of SBA that resulted from recent research are discussed in this comprehensive review. RESULTS Genomic analysis has demonstrated that SBA is a molecularly unique intestinal cancer. Double balloon enteroscopy and capsule endoscopy are novel techniques which may result in earlier diagnosis and consequently in improvement of the generally poor prognosis. For clinically localized disease, the quality of surgery has recently been defined, with removal of at least 8-10 lymph nodes correlating with improved prognosis. Moreover, adjuvant chemotherapy seems to improve outcome of stage III disease. The combination of a fluoropyrimidine and oxaliplatin appears to be the most effective systemic chemotherapy for disseminated disease. Genomic profiling can identify potentially targetable genomic alterations in a significant proportion of SBA patients. The role of administration of targeted agents or immune checkpoint inhibitors is still unknown and subject of ongoing clinical trials. In the common case of peritoneal metastases, recent studies have shown that cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy may be an attractive treatment option in selected patients. CONCLUSIONS SBA is a rare and unique malignancy, whose diagnostic approach and treatment are evolving, resulting in improved outcome.
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Affiliation(s)
- Eelco de Bree
- a Department of Surgical Oncology , Medical School of Crete University Hospital , Heraklion , Greece
| | - Koen P Rovers
- b Department of Surgical Oncology , Catharina Hospital , Eindhoven , The Netherlands
| | - Dimitris Stamatiou
- a Department of Surgical Oncology , Medical School of Crete University Hospital , Heraklion , Greece
| | - John Souglakos
- c Department of Medical Oncology and Laboratory of Translational Oncology , Medical School of Crete University Hospital , Heraklion , Greece
| | - Dimosthenis Michelakis
- a Department of Surgical Oncology , Medical School of Crete University Hospital , Heraklion , Greece
| | - Ignace H de Hingh
- b Department of Surgical Oncology , Catharina Hospital , Eindhoven , The Netherlands
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21
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Schrock AB, Devoe CE, McWilliams R, Sun J, Aparicio T, Stephens PJ, Ross JS, Wilson R, Miller VA, Ali SM, Overman MJ. Genomic Profiling of Small-Bowel Adenocarcinoma. JAMA Oncol 2017; 3:1546-1553. [PMID: 28617917 PMCID: PMC5710195 DOI: 10.1001/jamaoncol.2017.1051] [Citation(s) in RCA: 151] [Impact Index Per Article: 18.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2017] [Accepted: 03/21/2017] [Indexed: 12/17/2022]
Abstract
IMPORTANCE Small-bowel adenocarcinomas (SBAs) are rare cancers with a significantly lower incidence, later stage at diagnosis, and worse overall survival than other intestinal-derived cancers. To date, comprehensive genomic analysis of SBA is lacking. OBJECTIVE To perform in-depth genomic characterization of a large series of SBAs and other gastrointestinal tumors to draw comparisons and identify potentially clinically actionable alterations. DESIGN, SETTING, AND PARTICIPANTS Prospective analysis was performed of clinical samples from patients with SBA (n = 317), colorectal cancer (n = 6353), and gastric carcinoma (n = 889) collected between August 24, 2012, and February 3, 2016, using hybrid-capture-based genomic profiling, at the request of the individual treating physicians in the course of clinical care for the purpose of making therapy decisions. RESULTS Of the 7559 patients included in analysis, 4138 (54.7%) were male; the median age was 56 (range, 12-101) years. The frequency of genomic alterations seen in SBA demonstrated distinct differences in comparison with either colorectal cancer (APC: 26.8% [85 of 317] vs 75.9% [4823 of 6353], P < .001; and CDKN2A: 14.5% [46 of 317] vs 2.6% [165 of 6353], P < .001) or gastric carcinoma (KRAS: 53.6% [170 of 317] vs 14.2% [126 of 889], P < .001; APC: 26.8% [85 of 317] vs 7.8% [69 of 889], P < .001; and SMAD4: 17.4% [55 of 317] vs 5.2% [46 of 889], P < .001). BRAF was mutated in 7.6% (484 of 6353) of colorectal cancer and 9.1% (29 of 317) of SBA samples, but V600E mutations were much less common in SBA, representing only 10.3% (3 of 29) of BRAF-mutated cases. The ERBB2/HER2 point mutations (8.2% [26 of 317]), microsatellite instability (7.6% [13 of 170]), and high tumor mutational burden (9.5% [30 of 317]) were all enriched in SBA. Significant differences were noted in the molecular profile of unspecified SBA compared with duodenal adenocarcinoma, as well as in inflammatory bowel disease-associated SBAs. Targetable alterations in several additional genes, including PIK3CA and MEK1, and receptor tyrosine kinase fusions, were also identified in all 3 series. CONCLUSIONS AND RELEVANCE This study presents to our knowledge the first large-scale genomic comparison of SBA with colorectal cancer and gastric carcinoma. The distinct genomic differences establish SBA as a molecularly unique intestinal cancer. In addition, genomic profiling can identify potentially targetable genomic alterations in the majority of SBA cases (91%), and the higher incidence of microsatellite instability and tumor mutational burden in SBA suggests a potential role for immunotherapy.
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Affiliation(s)
| | - Craig E. Devoe
- Northwell Health, The Monter Cancer Center, Lake Success, New York
| | | | - James Sun
- Foundation Medicine, Inc, Cambridge, Massachusetts
| | - Thomas Aparicio
- Gastroenterology and Digestive Oncology, Centre Hospitalo-Universitaire Avicenne, Assistance Publique Hôpitaux de Paris, University Paris 13, Bobigny, France
| | | | - Jeffrey S. Ross
- Foundation Medicine, Inc, Cambridge, Massachusetts
- Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York
| | - Richard Wilson
- Centre for Cancer Research and Cell Biology, Queen's University Belfast, Northern Ireland
| | | | - Siraj M. Ali
- Foundation Medicine, Inc, Cambridge, Massachusetts
| | - Michael J. Overman
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston
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22
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Wilhelm A, Galata C, Beutner U, Schmied BM, Warschkow R, Steffen T, Brunner W, Post S, Marti L. Duodenal localization is a negative predictor of survival after small bowel adenocarcinoma resection: A population-based, propensity score-matched analysis. J Surg Oncol 2017; 117:397-408. [DOI: 10.1002/jso.24877] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Revised: 09/09/2017] [Accepted: 09/18/2017] [Indexed: 12/12/2022]
Affiliation(s)
| | - Christian Galata
- Department of Surgery; Universitätsmedizin Mannheim, Medical Faculty Mannheim, University of Heidelberg; Mannheim Germany
| | - Ulrich Beutner
- Department of General, Visceral, Endocrine and Transplantation Surgery; Kantonsspital St. Gallen; St. Gallen Switzerland
| | - Bruno M. Schmied
- Department of General, Visceral, Endocrine and Transplantation Surgery; Kantonsspital St. Gallen; St. Gallen Switzerland
| | - Rene Warschkow
- Department of General, Visceral, Endocrine and Transplantation Surgery; Kantonsspital St. Gallen; St. Gallen Switzerland
- Institute of Medical Biometry and Informatics; University of Heidelberg; Heidelberg Germany
| | - Thomas Steffen
- Department of General, Visceral, Endocrine and Transplantation Surgery; Kantonsspital St. Gallen; St. Gallen Switzerland
| | - Walter Brunner
- Department of General, Visceral, Endocrine and Transplantation Surgery; Kantonsspital St. Gallen; St. Gallen Switzerland
| | - Stefan Post
- Department of Surgery; Universitätsmedizin Mannheim, Medical Faculty Mannheim, University of Heidelberg; Mannheim Germany
| | - Lukas Marti
- Department of Surgery; Universitätsmedizin Mannheim, Medical Faculty Mannheim, University of Heidelberg; Mannheim Germany
- Department of General, Visceral, Endocrine and Transplantation Surgery; Kantonsspital St. Gallen; St. Gallen Switzerland
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23
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Hirao M, Komori M, Nishida T, Iijima H, Yamaguchi S, Ishihara R, Yasunaga Y, Kobayashi I, Kishida O, Oshita M, Hagiwara H, Ito T, Suzuki K, Hayashi Y, Inoue T, Tsujii M, Yoshihara H, Takehara T. Clinical use of molecular targeted agents for primary small bowel adenocarcinoma: A multicenter retrospective cohort study by the Osaka Gut Forum. Oncol Lett 2017; 14:1628-1636. [PMID: 28789389 PMCID: PMC5529922 DOI: 10.3892/ol.2017.6290] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Accepted: 03/03/2017] [Indexed: 01/05/2023] Open
Abstract
Primary small bowel adenocarcinoma (SBA) is a rare cancer for which effective treatment strategies have not yet been established. The results of previous retrospective studies suggest that chemotherapy contributes to a longer survival time in patients with SBA. However, there are few case reports about the efficacy of molecular targeted agent-containing chemotherapy for SBA. In the present study, the treatment and follow-up data of patients with SBA who received chemotherapy with or without molecular targeted agents were retrospectively analyzed. Each patient was treated in one of ten hospitals participating in the Osaka Gut Forum between April 2006 and March 2014. The following factors were evaluated: Age, sex, Eastern Cooperative Oncology Group performance status (PS), tumor location, tumor differentiation, chemotherapy regimen, resection of primary tumor, tumor biomarker expression, distant metastasis, best response under chemotherapy, time to disease progression, subsequent treatments, survival status and treatment toxicity. A total of 27 patients (17 males and 10 females; mean age, 63.4 years old; range, 36-83 years old) received chemotherapy due to non-curative tumor resection, unresectable tumor or post-operative recurrence. The median overall survival time was 14.8 months (range, 2-58 months). A univariate analysis revealed a PS of 0 (P=0.0228) and treatment with platinum-based chemotherapy (P=0.0048) were significant factors for an improved prognosis. An age-adjusted multivariate analysis also revealed that a platinum-based regimen was a significant positive prognostic factor (P=0.0373). Molecular targeted agents were administered to 8 patients, for whom it was their first- or second-line therapy. Among the 17 patients who received oxaliplatin-based chemotherapy as a first-line chemotherapy, a PS of 0 (P=0.0255) and treatment with bevacizumab (P=0.0121) were significant positive prognostic factors. Toxicities higher than Grade 3 occurred in 8/27 patients with SBA; however, serious side effects due to the molecular targeted agents were not experienced. The results of the present study indicate that chemotherapy containing molecular targeted agents is a well-tolerated and effective treatment option for SBA.
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Affiliation(s)
- Motohiro Hirao
- Department of Gastroenterology, Osaka Rosai Hospital, Sakai, Osaka 591-8025, Japan
| | - Masato Komori
- Department of Gastroenterology, Osaka Rosai Hospital, Sakai, Osaka 591-8025, Japan
| | - Tsutomu Nishida
- Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Osaka 560-8565, Japan
| | - Hideki Iijima
- Department of Gastroenterology and Hepatology, Osaka University, Suita, Osaka 565-0871, Japan
| | - Shinjiro Yamaguchi
- Department of Gastroenterology, Kansai Rosai Hospital, Amagasaki, Hyogo 660-8511, Japan
| | - Ryu Ishihara
- Department of Gastroenterology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka 537-8511, Japan
| | - Yuichi Yasunaga
- Department of Gastroenterology, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo 662-0918, Japan
| | - Ichizo Kobayashi
- Department of Gastroenterology, Higashiosaka City General Hospital, Higashiosaka, Osaka 578-8588, Japan
| | - Osamu Kishida
- Department of Gastroenterology, Sumitomo Hospital, Nakanoshima, Osaka 530-0005, Japan
| | - Masahide Oshita
- Department of Gastroenterology, Osaka Police Hospital, Osaka 543-0035, Japan
| | - Hideki Hagiwara
- Department of Gastroenterology, Kansai Rosai Hospital, Amagasaki, Hyogo 660-8511, Japan
| | - Toshifumi Ito
- Department of Internal Medicine, Japan Community Healthcare Organization Osaka Hospital, Osaka 553-0003, Japan
| | - Kunio Suzuki
- Department of Gastroenterology, Saiseikai Senri Hospital, Suita, Osaka 565-0862, Japan
| | - Yoshito Hayashi
- Department of Gastroenterology and Hepatology, Osaka University, Suita, Osaka 565-0871, Japan
| | - Takahiro Inoue
- Department of Gastroenterology and Hepatology, Osaka University, Suita, Osaka 565-0871, Japan
| | - Masahiko Tsujii
- Department of Gastroenterology, Higashiosaka City General Hospital, Higashiosaka, Osaka 578-8588, Japan
| | - Harumasa Yoshihara
- Department of Gastroenterology, Kaizuka City Hospital, Kaizuka, Osaka 597-0015, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University, Suita, Osaka 565-0871, Japan
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24
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Difference Makers: Chromosomal Instability versus Aneuploidy in Cancer. Trends Cancer 2016; 2:561-571. [DOI: 10.1016/j.trecan.2016.09.003] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Revised: 08/26/2016] [Accepted: 09/01/2016] [Indexed: 01/06/2023]
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Abstract
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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Affiliation(s)
- Michael J Overman
- From the Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
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26
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Treatment and Survival of Small-bowel Adenocarcinoma in the United States: A Comparison With Colon Cancer. Dis Colon Rectum 2016; 59:306-15. [PMID: 26953989 DOI: 10.1097/dcr.0000000000000562] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Small-bowel adenocarcinoma is rare and fatal. Because of data paucity, there is a tendency to extrapolate treatment from colon cancer, particularly in the adjuvant stetting. OBJECTIVE The purpose of this study was to evaluate the current surgical and adjuvant treatments of small-bowel adenocarcinoma and compare with colon cancer. DESIGN This was a retrospective cohort study. SETTINGS The linked Surveillance, Epidemiology, and End Results and Medicare database was used at a tertiary referral hospital. PATIENTS Patients with small-bowel adenocarcinoma and colon cancer identified from 1992 to 2010, using International Classification of Diseases for Oncology, 3 Revision, site, behavior, and histology codes were included. MAIN OUTCOME MEASURES Overall survival and cancer-specific survival were estimated using the Kaplan-Meier method and competing risk analysis. RESULTS A total of 2123 patients with small-bowel adenocarcinoma and 248,862 patients with colon cancer were identified. Five-year overall survival rates for patients with small-bowel adenocarcinoma and colon cancer were 34.9% and 51.5% (p < 0.0001). A total of 1550 patients with small-bowel adenocarcinoma (73.0%) underwent surgery, compared with 177,017 patients with colon cancer (71.1%). The proportion of patients who received chemotherapy was similar, at 21.3% for small bowel and 20.0% for colon. In contrast to colon cancer, chemotherapy did not improve overall or cancer-specific survival for patients with small-bowel adenocarcinoma, regardless of stage. Predictors of poor survival for small-bowel adenocarcinoma on multivariate analysis included advanced age, black race, advanced stage, poor tumor differentiation, high comorbidity index, and distal location. Chemotherapy did not confer additional survival benefit compared with surgery alone (HR, 1.04 (95% CI, 0.90-1.22)). LIMITATIONS This was a retrospective review. The reliance on Medicare data limited granularity and may have affected the generalizability of the results. CONCLUSIONS The prognosis for small-bowel adenocarcinoma is worse than that for colon cancer, and only surgery improves survival. In contrast to colon cancer, a survival benefit from current chemotherapy regimens for small-bowel adenocarcinoma is not seen, suggesting that it may be overused and needs more rigorous study.
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27
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Unusual case of primary adenocarcinoma of the small bowel and lung occurring in a patient: a case report and review of literature. J Gastrointest Cancer 2014; 46:80-4. [PMID: 25544364 DOI: 10.1007/s12029-014-9677-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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28
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Shenoy S. Primary small-bowel malignancy: update in tumor biology, markers, and management strategies. J Gastrointest Cancer 2014; 45:421-430. [PMID: 25339426 DOI: 10.1007/s12029-014-9658-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE Primary small-bowel malignancies (SBM) are rare tumors but their incidence is rising. An estimated 9160 new cases and 1210 deaths due to SBM may occur in the USA in 2014. We review advances made in tumor biology, immunohistochemistry, and discuss treatment strategies for these malignancies. METHODS Relevant articles from PubMed/Medline and Embase searches were collected using the phrases "small-bowel adenocarcinoma, gastrointestinal carcinoids, gastrointestinal stromal tumors, small-bowel leiomyosarcoma, and small-bowel lymphoma". RESULTS Advances in imaging techniques such as wireless capsule endoscopy, CT and MRI enterography, and endoscopy (balloon enteroscopy) along with discovery of molecular markers such as c-kit and PDGFRA for GIST tumors have improved our ability to diagnose, localize, and treat these patients. Early detection and surgical resection offers the best chance for long-term survival in all tumors except bowel lymphoma where chemotherapy plays the main role. Adjuvant therapy with imatinib has improved overall survival for GIST tumors, somatostatin analogs have improved symptoms and also inhibited tumor growth and stabilized metastatic disease in carcinoid disease, but chemotherapy has not improved survival for adenocarcinoma. CONCLUSIONS Recent advances in molecular characterization holds promise in novel targeted therapies. Currently ongoing trials are exploring efficacy of targeted therapies and role of adjuvant therapy for adenocarcinoma and results are awaited. Early detection and aggressive surgical therapy for all localized tumors and lymph node sampling particularly for adenocarcinoma remains the main treatment modality.
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Affiliation(s)
- Santosh Shenoy
- Department of Surgery, KCVA, 4801 E Linwood Blvd, Kansas City, MO, 64128, USA,
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29
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Aparicio T, Svrcek M, Zaanan A, Beohou E, Laforest A, Afchain P, Mitry E, Taieb J, Di Fiore F, Gornet JM, Thirot-Bidault A, Sobhani I, Malka D, Lecomte T, Locher C, Bonnetain F, Laurent-Puig P. Small bowel adenocarcinoma phenotyping, a clinicobiological prognostic study. Br J Cancer 2013; 109:3057-66. [PMID: 24196786 PMCID: PMC3859950 DOI: 10.1038/bjc.2013.677] [Citation(s) in RCA: 89] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2013] [Revised: 10/01/2013] [Accepted: 10/03/2013] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Small bowel adenocarcinoma (SBA) is a rare tumour with a poor prognosis. Molecular biology data on SBA carcinogenesis are lacking. METHODS Expression of HER2, β-catenin, p53 and mismatch repair (MMR) protein was assessed by immunohistochemistry. KRAS, V600E BRAF mutations and microsatellite instability were investigated. RESULTS We obtained samples from 63 SBA patients (tumour stages: I-II: 30%; III: 35%; IV: 32%; locally advanced: 3%). HER2 overexpression (3+) was observed in 2 out of 62 patients, overexpression of p53 in 26 out of 62, abnormal expression of β-catenin in 12 out of 61, KRAS mutation in 21 out of 49, BRAF V600E mutation in 1 out of 40 patients, MMR deficiency (dMMR) in 14 out of 61 and was consistent with Lynch syndrome in 9 out of 14 patients. All of the dMMR tumours were in the duodenum or jejunum and only one was stage IV. Median overall survival (OS) was 36.6 months (95% CI, 26.9-72.2). For all patients, in univariate analysis, stages I-II (P<0.001), WHO PS 0-1 (P=0.01) and dMMR phenotype (P=0.02) were significantly associated with longer OS. In multivariate analysis, disease stage (P=0.01) and WHO PS 0-1 (P=0.001) independently predicted longer OS. For stage IV patients, median OS was 20.5 months (95% CI: 14.6; 36.6 months). In multivariate analysis, WHO PS 0-1 (P=0.0001) and mutated KRAS status (P=0.02) independently predicted longer OS. CONCLUSION 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 frequencies of KRAS mutations. The seemingly higher frequency of dMMR than in CRC may be explained by the higher frequency of Lynch syndrome in SBA patients. A dMMR phenotype was significantly associated with a non-metastatic tumour (P=0.02). A trend for a good prognosis and a duodenum or jejunum primary site was associated with dMMR.
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Affiliation(s)
- T Aparicio
- Gastroenterology and Digestive Oncology, APHP, Hôpitaux Universitaires de Seine Saint Denis, Avicenne Hospital, University Paris 13, Paris Sorbonne Cité, 125 rue de Stalingrad, Bobigny 93000, France
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Abstract
Small bowel cancers account for 3% of all gastrointestinal malignancies and small bowel adenocarcinomas represent a third of all small bowel cancers. Rarity of small bowel adenocarcinomas restricts molecular understanding and presents unique diagnostic and therapeutic challenges. Better cross-sectional imaging techniques and development of enteroscopy and capsule endoscopy have facilitated earlier and more-accurate diagnosis. Surgical resection remains the mainstay of therapy for locoregional disease. In the metastatic setting, fluoropyrimidine and oxaliplatin-based chemotherapy has shown clinical benefit in prospective non-randomized trials. Although frequently grouped under the same therapeutic umbrella as large bowel adenocarcinomas, small bowel adenocarcinomas are distinct clinical and molecular entities. Recent progress in molecular characterization has aided our understanding of the pathogenesis of these tumours and holds potential for prospective development of novel targeted therapies. Multi-institutional collaborative efforts directed towards cogent understanding of tumour biology and designing sensible clinical trials are essential for developing improved therapeutic strategies. In this Review, we endeavour to outline an evidence-based approach to present-day management of small bowel adenocarcinoma, describe contemporary challenges and uncover evolving paradigms in the management of these rare 'orphan' neoplasias.
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Affiliation(s)
- Kanwal Raghav
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Centre, Unit #426, 1515 Holcombe Boulevard, Houston, TX 77030, USA
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Ascierto PA, Simeone E, Grimaldi AM, Curvietto M, Esposito A, Palmieri G, Mozzillo N. Do BRAF inhibitors select for populations with different disease progression kinetics? J Transl Med 2013; 11:61. [PMID: 23497384 PMCID: PMC3599508 DOI: 10.1186/1479-5876-11-61] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2013] [Accepted: 03/04/2013] [Indexed: 11/10/2022] Open
Abstract
Ipilimumab, an anti-CTLA-4 monoclonal antibody, has been shown to improve overall survival in patients with metastatic melanoma. Preliminary data suggest that patients who fail BRAF inhibitor treatment experience a very rapid progression of disease. Such selectivity for more rapid disease progression may mean these patients do not receive the same benefit from subsequent treatment with ipilimumab as patients without prior BRAF inhibitor treatment. The current challenge is focused on how to identify and approach the two populations of fast and slow progressors and recent hypothesis suggest that treatment choice could be guided by baseline risk factors. However, no data have yet defined which the best sequence is and more research is needed to identify predictors of response in patients with metastatic melanoma to help guide whether a BRAF inhibitor or ipilimumab should be used first in sequential therapy.
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Affiliation(s)
- Paolo Antonio Ascierto
- Unit of Melanoma, Cancer Immunotherapy and Innovative Therapy, Department of Melanoma, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy.
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Halfdanarson TR, Grothey A. Establishing a standard of care for small bowel adenocarcinomas: challenges and lessons learned. Oncologist 2012; 17:1133-4. [PMID: 22923454 DOI: 10.1634/theoncologist.2012-0323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Arber N, Moshkowitz M. Small Intestinal Cancers. HANDBOOK OF GASTROINTESTINAL CANCER 2012:67-85. [DOI: 10.1002/9781118423318.ch4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Tsushima T, Taguri M, Honma Y, Takahashi H, Ueda S, Nishina T, Kawai H, Kato S, Suenaga M, Tamura F, Morita S, Boku N. Multicenter retrospective study of 132 patients with unresectable small bowel adenocarcinoma treated with chemotherapy. Oncologist 2012; 17:1163-70. [PMID: 22622149 DOI: 10.1634/theoncologist.2012-0079] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND No standard chemotherapy regimen has been established for unresectable or recurrent small bowel adenocarcinoma (SBA). METHODS Clinical courses of 132 patients with unresectable or recurrent SBA who received chemotherapy at 41 institutions in Japan were reviewed retrospectively. Patients were classified into five groups according to first-line chemotherapy regimens: fluoropyrimidine monotherapy (group A), fluoropyrimidine-cisplatin (group B), fluoropyrimidine-oxaliplatin (group C), fluoropyrimidine-irinotecan (group D), and other regimens (group E). RESULTS The number of patients in each group was as follows: groups A, 60 patients; group B, 17 patients; group C, 22 patients; group D, 11 patients; and group E, 22 patients. Median progression-free survival (PFS) times were as follows: group A, 5.4 months; group B, 3.8 months; group C, 8.2 months; group D, 5.6 months; and group E, 3.4 months. Median overall survival (OS) times were as follows: group A, 13.9 months; group B, 12.6 months; group C, 22.2 months; group D, 9.4 months; and group D, 8.1 months. Patients in group C achieved significantly longer PFS times and substantially (but not significantly) longer OS times than patients in group A. After adjusting for clinical background characteristics, fluoropyrimidine-oxaliplatin therapy was a significant positive prognostic factor for PFS and OS times. CONCLUSION The results suggest that fluoropyrimidine-oxaliplatin combination therapy is the most promising first-line chemotherapy regimen for unresectable or recurrent SBA.
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Affiliation(s)
- Takahiro Tsushima
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho Sunto-gun, Shizuoka, Japan.
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