Journal ArticleDOI
Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer
Gordon G A Hutchins,K Southward,Kelly Handley,Laura Magill,C Beaumont,Jens Stahlschmidt,Susan D. Richman,Philip A. Chambers,Matthew T. Seymour,David J. Kerr,Richard Gray,Philip Quirke +11 more
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The usefulness of defective mismatch repair, BRAF, and KRAS mutations in predicting tumor recurrence and sensitivity to chemotherapy is investigated and MMR assays identify patients with a low risk of recurrence.Abstract:
Purpose It is uncertain whether modest benefits from adjuvant chemotherapy in stage II colorectal cancer justify the toxicity, cost, and inconvenience. We investigated the usefulness of defective mismatch repair (dMMR), BRAF, and KRAS mutations in predicting tumor recurrence and sensitivity to chemotherapy. Patients and Methods Immunohistochemistry for dMMR and pyrosequencing for KRAS/BRAF were performed for 1,913 patients randomly assigned between fluorouracil and folinic acid chemotherapy and no chemotherapy in the Quick and Simple and Reliable (QUASAR) trial. Results Twenty-six percent of 695 right-sided colon, 3% of 685 left-sided colon, and 1% of 407 rectal tumors were dMMR. Similarly, 17% of right colon, 2% of left colon, and 2% of rectal tumors were BRAF mutant. KRAS mutant tumors were more evenly distributed: 40% right colon, 28% left colon, and 36% rectal tumors. Recurrence rate for dMMR tumors was half that for MMR-proficient tumors (11% [25 of 218] v 26% [438 of 1,695] recurred; risk ratio [RR]...read more
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ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making
H.-J. Schmoll,E. Van Cutsem,Alexander Stein,Vincenzo Valentini,Bengt Glimelius,Bengt Glimelius,Karin Haustermans,Bernard Nordlinger,C.J.H. van de Velde,Judith Balmaña,Jaroslaw Regula,Iris D. Nagtegaal,Regina G. H. Beets-Tan,D Arnold,Fortunato Ciardiello,Paulo M. Hoff,David J. Kerr,C.-H. Köhne,Roberto Labianca,Timothy J. Price,Werner Scheithauer,Alberto Sobrero,Josep Tabernero,Dan Aderka,S Barroso,György Bodoky,J.-Y. Douillard,H El Ghazaly,Jorge Gallardo,August Garin,Rob Glynne-Jones,Karin Jordan,A Meshcheryakov,D Papamichail,Per Pfeiffer,Ioannis Souglakos,Serdar Turhal,Andrés Cervantes +37 more
TL;DR: This ESMO guideline is recommended to be used as the basis for treatment and management decisions, delivering a clear proposal for diagnostic and treatment measures in each stage of rectal and colon cancer and the individual clinical situations.
Journal ArticleDOI
Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value
Laetitia Marisa,Aurélien de Reyniès,Alex Duval,Alex Duval,Janick Selves,Marie Pierre Gaub,Laure Vescovo,Marie-Christine Etienne-Grimaldi,Renaud Schiappa,Dominique Guenot,Mira Ayadi,Sylvain Kirzin,Maurice Chazal,Jean-François Fléjou,Jean-François Fléjou,Daniel Benchimol,Anne Berger,Arnaud Lagarde,Erwan Pencreach,F. Piard,Dominique Elias,Yann Parc,Sylviane Olschwang,Gérard Milano,Pierre Laurent-Puig,Valérie Boige,Valérie Boige +26 more
TL;DR: A new classification of CC into six molecular subtypes that arise through distinct biological pathways that improves the current disease stratification based on clinicopathological variables and common DNA markers is described.
Journal ArticleDOI
EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib
Ryan B. Corcoran,Hiromichi Ebi,Alexa B. Turke,Erin M. Coffee,Michiya Nishino,Alexandria P. Cogdill,Ronald D. Brown,Patricia Della Pelle,Dora Dias-Santagata,Kenneth E. Hung,Keith T. Flaherty,Adriano Piris,Jennifer A. Wargo,Jeffrey Settleman,Mari Mino-Kenudson,Jeffrey A. Engelman +15 more
TL;DR: It is found that EGFR-mediated MAPK pathway reactivation leads to resistance to vemurafenib in BRAF-mutant colorectal cancers and that combined RAF and EGFR inhibition can lead to sustainedMAPK pathway suppression and improved efficacy in vitro and in tumor xenografts.
Journal ArticleDOI
Prognostic Survival Associated With Left-Sided vs Right-Sided Colon Cancer: A Systematic Review and Meta-analysis
Fausto Petrelli,Gianluca Tomasello,Karen Borgonovo,Michele Ghidini,Luca Turati,Pierpaolo Dallera,Rodolfo Passalacqua,Giovanni Sgroi,Sandro Barni +8 more
TL;DR: CC side should be acknowledged as a criterion for establishing prognosis in all stages of disease, and should represent a stratification factor for future adjuvant studies.
Journal ArticleDOI
Adjuvant Fluorouracil, Leucovorin, and Oxaliplatin in Stage II to III Colon Cancer: Updated 10-Year Survival and Outcomes According to BRAF Mutation and Mismatch Repair Status of the MOSAIC Study
Thierry André,Armand de Gramont,Dewi Vernerey,Benoist Chibaudel,Franck Bonnetain,Annemilaï Tijeras-Raballand,Aurelie Scriva,Tamas Hickish,Josep Tabernero,Jean-Luc Van Laethem,Maria Banzi,E. Maartense,Einat Shacham Shmueli,Göran Carlsson,Werner Scheithauer,Demetris Papamichael,Marcus Möehler,Stefania Landolfi,Pieter Demetter,Soudhir Colote,Christophe Tournigand,Christophe Louvet,Alex Duval,Jean François Fléjou,Aimery de Gramont +24 more
TL;DR: The OS benefit of oxaliplatin-based adjuvant chemotherapy, increasing over time and with the disease severity, was confirmed at 10 years in patients with stage II to III colon cancer, and updated results support the use of FOLFOX in Patients with stage III disease, including those with dMMR or BRAF mutation.
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TL;DR: The 10-year and 15-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival are reported and it is found that the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis.
Journal ArticleDOI
American Society of Clinical Oncology 2007 Update of Recommendations for the Use of Tumor Markers in Breast Cancer
Lyndsay Harris,Herbert A. Fritsche,Robert G. Mennel,Larry Norton,Peter M. Ravdin,Sheila E. Taube,Mark R. Somerfield,Daniel F. Hayes,Robert C. Bast +8 more
TL;DR: Thirteen categories of breast tumor markers were considered, six of which were new for the guideline, and certain multiparameter gene expression assays not all applications for these markers were supported, however.
Journal ArticleDOI
Systematic Review of Microsatellite Instability and Colorectal Cancer Prognosis
TL;DR: CRCs with MSI have a significantly better prognosis compared to those with intact mismatch repair, and additional studies are needed to further define the benefit of adjuvant chemotherapy in locally advanced tumors with MSI.
Journal ArticleDOI
Wild-Type BRAF Is Required for Response to Panitumumab or Cetuximab in Metastatic Colorectal Cancer
Federica Di Nicolantonio,Miriam Martini,Francesca Molinari,Andrea Sartore-Bianchi,Sabrina Arena,Piercarlo Saletti,Sara De Dosso,Luca Mazzucchelli,Milo Frattini,Salvatore Siena,Alberto Bardelli +10 more
TL;DR: BRAF wild-type is required for response to panitumumab or cetuximab and could be used to select patients who are eligible for the treatment and should be used for selection.
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