Article
Medical Laboratory Technology
Chengfeng Wang, Diling Pan
Summary: This study investigated the relationship between BRAF, KRAS, and PIK3CA mutations and clinicopathologic features and prognosis of colorectal cancer patients. The results showed that the mutant patterns of BRAF, KRAS, and PIK3CA were not associated with the general and clinicopathological features of patients. However, these mutation patterns could be used as independent prognostic factors for colorectal cancer.
JOURNAL OF CLINICAL LABORATORY ANALYSIS
(2022)
Review
Oncology
Junjia Liu, Hao Xie
Summary: This review explores the characteristics, clinical relevance, and treatment possibilities of BRAF non-V600 mutations in colorectal cancer, filling in existing knowledge gaps. Understanding the intricacies of these mutations can help healthcare professionals and researchers develop personalized treatment strategies to improve patient care.
Review
Biochemistry & Molecular Biology
Ahmad Machmouchi, Laudy Chehade, Sally Temraz, Ali Shamseddine
Summary: Targeted monoclonal antibody therapy against EGFR is a leading treatment for mCRC. However, resistance due to KRAS and BRAF mutations has emerged. Cells with these mutations overexpress GLUT1 and SVCT2, leading to intracellular vitamin C transport and cell death. High dose vitamin C shows promise in overcoming EGFR resistance in mCRC with wild KRAS mutation and in patients with KRAS and BRAF mutations, but more clinical trials are needed.
Article
Multidisciplinary Sciences
Kristiaan J. Lenos, Sander Bach, Leandro Ferreira Moreno, Sanne ten Hoorn, Nina R. Sluiter, Sanne Bootsma, Felipe A. Vieira Braga, Lisanne E. Nijman, Tom van den Bosch, Daniel M. Miedema, Erik van Dijk, Bauke Ylstra, Ruth Kulicke, Fred P. Davis, Nicolas Stransky, Gromoslaw A. Smolen, Robert R. J. Coebergh van den Braak, Jan N. M. IJzermans, John W. M. Martens, Sally Hallam, Andrew D. Beggs, Geert J. P. L. Kops, Nico Lansu, Vivian P. Bastiaenen, Charlotte E. L. Klaver, Maria C. Lecca, Khalid El Makrini, Clara C. Elbers, Mark P. G. Dings, Carel J. M. van Noesel, Onno Kranenburg, Jan Paul Medema, Jan Koster, Lianne Koens, Cornelis J. A. Punt, Pieter J. Tanis, Ignace H. de Hingh, Maarten F. Bijlsma, Jurriaan B. Tuynman, Louis Vermeulen
Summary: A significant proportion of colorectal cancer patients develop peritoneal metastases, which are associated with poor disease outcome. This study characterizes peritoneal metastases from 52 patients and identifies a distinct molecular subtype. The researchers also discover the key role of the structural protein Moesin in peritoneal dissemination and confirm that polyclonal metastatic seeding underlies these lesions.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Hiroyuki Takeda, Yu Sunakawa
Summary: BRAF mutations are an important poor prognostic factor in mCRC, but greater understanding of patient characteristics through genomic classification allows for more ideal treatment strategies.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Elisa Grassi, Jody Corbelli, Giorgio Papiani, Maria Aurelia Barbera, Federica Gazzaneo, Stefano Tamberi
Summary: 8-12% of patients with advanced colon rectal cancer present with BRAF alterations, particularly the V600E mutation, which is associated with poor prognosis. New therapeutic options, such as targeted therapy combinations, are emerging for this subgroup of patients. Treatment optimization for this subgroup is an important goal.
FRONTIERS IN ONCOLOGY
(2021)
Article
Genetics & Heredity
Peter W. Eide, Seyed H. Moosavi, Ina A. Eilertsen, Tuva H. Brunsell, Jonas Langerud, Kaja C. G. Berg, Bard I. Rosok, Bjorn A. Bjornbeth, Arild Nesbakken, Ragnhild A. Lothe, Anita Sveen
Summary: Gene expression-based subtypes of colorectal cancer have clinical significance, but the representativeness of primary tumors and consensus molecular subtypes (CMS) for metastatic cancers remains unclear. Metastases exhibit decreased CMS1/CMS3 signals and increased CMS4 signals, influenced by the microenvironment. The majority of classified metastases are CMS2 or CMS4, with subtype switching and inter-metastatic CMS heterogeneity being common.
NPJ GENOMIC MEDICINE
(2021)
Article
Oncology
Emerik Osterlund, Ari Ristimaki, Markus J. Makinen, Soili Kytola, Juha Kononen, Per Pfeiffer, Leena-Maija Soveri, Mauri Keinanen, Halfdan Sorbye, Luis Nunes, Tapio Salminen, Lasse Nieminen, Aki Uutela, Paivi Halonen, Annika Algars, Jari Sundstrom, Raija Kallio, Raija Ristamaki, Annamarja Lamminmaki, Hanna Stedt, Eetu Heerva, Teijo Kuopio, Tobias Sjoblom, Helena Isoniemi, Bengt Glimelius, Pia Osterlund
Summary: BRAF-V600E mutation is a negative prognostic and predictive biomarker in metastatic colorectal cancer. Non-V600E mutations (aBRAFmt) are rare and poorly understood. This study compared the mutation patterns and characteristics of aBRAFmt with other RAS/BRAF groups in three different cohorts. The study found that aBRAFmt represents a distinct subgroup with differences in clinicopathological features, and its prognosis is slightly better than BRAF-V600E but worse than RASmt and RAS & BRAFwt. aBRAFmt should not be a contraindication for metastasectomy.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Medicine, General & Internal
Bahar Saberzadeh-Ardestani, Jeremy C. Jones, Joleen M. Hubbard, Robert R. McWilliams, Thorvardur R. Halfdanarson, Qian Shi, Mohamad Bassam Sonbol, Jonathan Ticku, Zhaohui Jin, Frank A. Sinicrope
Summary: This cohort study found clinically significant prolongation of survival in older patients with dMMR mCRC who received first-line pembrolizumab monotherapy in routine clinical practice. Liver metastasis was associated with poorer survival compared to nonliver metastasis, indicating the importance of metastatic site in survival outcome.
Article
Biochemistry & Molecular Biology
Ivo Gokmen, Ebru Tastekin, Nazan Demir, Erkan Ozcan, Fahri Akgul, Muhammed Bekir Hacioglu, Bulent Erdogan, Sernaz Topaloglu, Irfan Cicin
Summary: The aim of this study was to investigate the incidence, molecular patterns, and associations with clinical parameters of KRAS/NRAS and BRAF mutations in colorectal cancer. KRAS mutation was the most common, with KRAS G12D being the most common mutation pattern. BRAF(V600E) was the most common BRAF mutation. Furthermore, there were associations observed between these mutations and age, gender, and tumor localization.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Pawel M. Potocki, Piotr Wojcik, Lukasz Chmura, Bartlomiej Goc, Marcin Fedewicz, Zofia Bielanska, Jakub Swadzba, Kamil Konopka, Lukasz Kwinta, Piotr J. Wysocki
Summary: BRAF V600E and KRAS mutations in colorectal cancer are associated with poor prognosis. Targeted therapies for BRAF V600E and KRAS G12C are being developed. A retrospective database was created to analyze the clinical characteristics of patients with metastatic CRC and these mutations. BRAF V600E was more prevalent in tumors with neuroendocrine features, while KRAS G12C was associated with left-sided primary tumors and brain metastases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Vlad-Adrian Afrasanie, Mihai-Vasile Marinca, Bogdan Gafton, Teodora Alexa-Stratulat, Alexandra Rusu, Eliza-Maria Froicu, Daniel Sur, Cristian Virgil Lungulescu, Larisa Popovici, Andrei-Vlad Lefter, Irina Afrasanie, Anca-Viorica Ivanov, Lucian Miron, Cristina Rusu
Summary: In this study, the frequency, distribution, coexistence, and clinicopathological and molecular correlations of RAS, BRAF, PIK3CA, and TP53 mutations were investigated in 104 patients with metastatic colorectal cancer from Northeastern Romania. TP53 was the most frequently mutated gene (73.1%), followed by KRAS (45.2%) and PIK3CA (6.7%). The study provides novel insights into genetic variations specific to the population from Northeastern Romania and enables the development of genetic profiles in a developing country with limited access to specialized genetic tests.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Emilie Hafliger, Alessandra Boccaccino, Alexandra Lapeyre-Prost, Audrey Perret, Claire Gallois, Maria Antista, Lorenzo Pilla, Thierry Lecomte, Mario Scartozzi, Emilie Soularue, Lisa Salvatore, Vincent Bourgeois, Massimiliano Salati, David Tougeron, Ludovic Evesque, Jean-Nicolas Vaillant, Reem El-Khoury, Sara Lonardi, Chiara Cremolini, Julien Taieb
Summary: The combination of anti-BRAF and anti-EGFRs shows efficacy in patients with BRAFm mCRC previously treated with an anti-EGFR agent. The results of this retrospective study suggest that this combination could be a valuable treatment option for patients with limited therapeutic alternatives.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Oncology
Giovanni Randon, Rossana Intini, Chiara Cremolini, Elena Elez, Michael J. Overman, Jeeyun Lee, Paolo Manca, Francesca Bergamo, Filippo Pagani, Maria Antista, Valentina Angerilli, Francisco Javier Ros Montana, Daniele Lavacchi, Alessandra Boccaccino, Giovanni Fuca, Silvia Brich, Laura Cattaneo, Matteo Fassan, Filippo Pietrantonio, Sara Lonardi
Summary: This study aims to investigate the genomic and immunohistochemical expression profiles associated with primary resistance to EGFR/BRAF targeted therapy in patients with BRAF-mutated and microsatellite stable (MSS) metastatic colorectal cancer. The results suggest that the location of the tumor, genomic alterations, and gene expression patterns are associated with resistance to targeted therapy. Patients with a higher tumor mutational burden (TMB) have limited benefits from the treatment and may have worse prognosis.
EUROPEAN JOURNAL OF CANCER
(2022)
Review
Oncology
Alessandro Ottaiano, Francesco Sabbatino, Francesco Perri, Marco Cascella, Roberto Sirica, Renato Patrone, Maurizio Capuozzo, Giovanni Savarese, Monica Ianniello, Nadia Petrillo, Luisa Circelli, Vincenza Granata, Massimiliano Berretta, Mariachiara Santorsola, Guglielmo Nasti
Summary: This review discusses the prognostic significance of the KRAS p.G12C mutation in metastatic colorectal cancer and highlights its potential as a promising therapeutic target. The aim is to increase awareness of the factors that can influence the clinical, prognostic, and therapeutic implications associated with distinct mutations within the same protein.
Article
Oncology
Martin Graversen, S. Detlefsen, A. P. Ainsworth, C. W. Fristrup, A. O. Knudsen, P. Pfeiffer, L. S. Tarpgaard, M. B. Mortensen
Summary: This study evaluated the Peritoneal Regression Grading score (PRGS) and its prognostic value in patients with peritoneal metastasis. The results showed that 61% of patients had a complete or major histological response after three PIPAC treatments, which was the only independent prognostic factor. PIPAC treatment can induce significant histological response and provide important prognostic information for patients.
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Eran van Veldhuisen, Sjors Klompmaker, Quisette P. Janssen, Mohammed Abu Hilal, Adnan Alseidi, Alberto Balduzzi, Gianpaolo Balzano, Claudio Bassi, Frederik Berrevoet, Morgan Bonds, Olivier R. Busch, Giovanni Butturini, Kevin C. Conlon, Isabella M. Frigerio, Giuseppe K. Fusai, Johan Gagniere, Oonagh Griffin, Thilo Hackert, Asif Halimi, Tobias Keck, Joerg Kleeff, Ulla Klaiber, Knut J. Labori, Mickael Lesurtel, Giuseppe Malleo, Marco V. Marino, I. Quintus Molenaar, Michael B. Mortensen, Andrej Nikov, Michele Pagnanelli, Rupaly Pande, Per Pfeiffer, Daniel Pietrasz, Elena Rangelova, Keith J. Roberts, Antonio Sa Cunha, Roberto Salvia, Oliver Strobel, Timo Tarvainen, Johanna W. Wilmink, Bas Groot Koerkamp, Marc G. Besselink
Summary: This international multicenter retrospective cohort study found that pancreatectomy after preoperative FOLFIRINOX chemotherapy is associated with favorable outcomes for patients with borderline resectable and locally advanced pancreatic cancer. The study also found that R0 resection and tumor differentiation are predictors of overall survival, while the number of preoperative chemotherapy cycles and the use of adjuvant chemotherapy are not associated with overall survival.
ANNALS OF SURGICAL ONCOLOGY
(2023)
Editorial Material
Oncology
M. Graversen, S. Detlefsen, A. P. Ainsworth, C. W. Fristrup, A. O. Knudsen, P. Pfeiffer, L. S. Tarpgaard, M. B. Mortensen
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Rikke Lovendahl Eefsen, Jim S. S. Larsen, Louise L. L. Klarskov, Rahim Altaf, Estrid Hogdall, Peter Ingeholm, Jakob Lykke, Dorte L. L. Nielsen, Per Pfeiffer, Laurids O. Poulsen, Camilla Qvortrup, Jakob V. V. Schou, Morten Mau-Sorensen, Kell Osterlind, Benny V. V. Jensen
Summary: Therapy with immune checkpoint inhibitors has shown effectiveness in patients with metastatic mismatch-repair deficient colorectal cancer. However, the data on neoadjuvant ICI treatment in locally advanced CRC patients are limited. A study in Danish oncological centers evaluated the use of preoperative pembrolizumab in 10 treatment-naive dMMR CRC patients, demonstrating feasibility and effectiveness.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Oncology
Gabor Liposits, Jesper Ryg, Halla Skuladottir, Stine B. Winther, Soren Moller, Eva Hofsli, Carl-Henrik Shah, Laurids ostergaard Poulsen, Ake Berglund, Camilla Qvortrup, Pia Osterlund, Bengt Glimelius, Halfdan Sorbye, Per Pfeiffer
Summary: This study explores the prognostic value of four functional status measures in vulnerable older patients with metastatic colorectal cancer (mCRC) receiving first-line palliative chemotherapy. The results show that ECOG performance status, frailty phenotype, G8, and VES-13 are all effective tools for assessing overall survival in these patients.
JOURNAL OF GERIATRIC ONCOLOGY
(2023)
Editorial Material
Oncology
M. Graversen, I. Rouvelas, A. P. Ainsworth, A. P. Bjarnesen, S. Detlefsen, S. B. Ellebaek, C. W. Fristrup, M. G. Liljefors, L. Lundell, M. Nilsson, P. Pfeiffer, L. S. Tarpgaard, A. Tsekrekos, M. B. Mortensen
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Louise Skau Rasmussen, Stine B. Winther, Inna M. Chen, Britta Weber, Lise Ventzel, Gabor Liposits, Julia Sidenius Johansen, Soenke Detlefsen, Ida Egendal, Susy Shim, Signe Christensen, Per Pfeiffer, Morten Ladekarl
Summary: This study aims to investigate whether reduced dose GemNab is superior to full dose Gem in patients with resectable pancreatic cancer. The study will explore various endpoints including progression-free survival, overall survival, overall response rate, quality of life, toxicity, and rate of hospitalizations. The correlation between blood inflammatory markers, circulating tumor DNA, tissue biomarkers, and chemotherapy resistance will also be studied, along with measures of frailty to assess personalized treatment allocation or interventions.
Article
Oncology
Tiuri E. Kroese, Hanneke W. M. van Laarhoven, Sebastian F. Schoppman, Pieter R. A. J. Deseyne, Eric van Cutsem., Karin Haustermans., Philippe. Nafteux, Melissa Thomas, Radka Obermannova, Hanna R. Mortensen, Marianne Nordsmark, Per Pfeiffer, Anneli Elme, Antoine Adenis, Guillaume Piessen, Christiane J. Bruns, Florian Lordick, Ines Gockel, Markus Moehler, Cihan Gani, Theodore Liakakos, John Reynolds, Alessio G. Morganti, Riccardo Rosati, Carlo Castoro, Francesco Cellini, Domenico D'Ugo, Franco Roviello, Maria Bencivenga, Giovanni de Manzoni, Mark I. van Berge Henegouwen, Maarten C. C. M. Hulshof, Jolanda van Dieren, Marieke Vollebergh, Johanna W. van Sandick, Paul Jeene, Christel T. Muijs, Marije Slingerland, Francine E. M. Voncken, Henk Hartgrink, Geert-Jan Creemers, Maurice J. C. van der Sangen, Grard Nieuwenhuijzen, Maaike Berbee, Marcel Verheij, Bas Wijnhoven, Laurens V. Beerepoot, Nadia H. Mohammad, Stella Mook, Jelle P. Ruurda, Piotr Kolodziejczyk, Wojciech P. Polkowski, Lucjan Wyrwicz, Maria Alsina, Manuel Pera, Tania F. Kanonnikoff, Andres Cervantes, Magnus Nilsson, Stefan Monig, Anna D. Wagner, Matthias Guckenberger, Ewen A. Griffiths, Elizabeth Smyth, George B. Hanna, Sheraz Markar, M. Asif Chaudry, Maria A. Hawkins, Edward Cheong, Richard van Hillegersberg, Peter S. N. van Rossum
Summary: This study aimed to develop a multidisciplinary European consensus statement on the definition, diagnosis and treatment of oligometastatic oesophago-gastric cancer. Through a series of discussions and expert evaluations, a consensus was reached, which can be used for future research in clinical trials.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Medicine, General & Internal
Tobias Freyberg Justesen, Ismail Gogenur, Line Schmidt Tarpgaard, Per Pfeiffer, Camilla Qvortrup
Summary: In the past two decades, there have been significant advances in the surgical approach for colorectal cancer patients. However, reducing surgery-related complications and improving long-term oncological outcomes still present challenges. Studies have shown promising response rates in immunotherapy for colorectal cancer patients with mismatch repair deficiency (dMMR). This study aims to investigate the effects of neoadjuvant immunotherapy and identify predictive biomarkers.
Article
Oncology
C. J. A. Punt, V. Heinemann, T. Maughan, C. Cremolini, E. Van Cutsem, R. McDermott, G. Bodoky, T. Andre, P. Osterlund, A. J. Teske, P. Pfeiffer
Summary: Fluoropyrimidines are widely used in the treatment of metastatic colorectal cancer. S-1, an oral fluoropyrimidine, has been approved for use as monotherapy or in combination with other drugs. An international group of oncologists formulated recommendations for the use of S-1 based on published data.
Article
Oncology
N. H. Paulsen, P. Pfeiffer, M. Ewertz, S. Feddersen, H. S. Holm, T. K. Bergmann, C. Qvortrup, P. Damkier
Summary: The study aimed to compare the frequency of grade >3 FP-TOX before and after the implementation of DPYD genotyping. The results showed that the overall frequency of grade >3 FP-TOX was 27% in the DPYD genotype-guided group compared to 24% in the historical cohort. DPYD genotyping reduced the frequency of FP-related hospitalization from 19% to 0% in DPYD variant carriers. In wild-type patients, those with uracil >16 ng/mL had a higher frequency of FP-TOX than those with uracil <16 ng/mL.
Article
Oncology
Emerik Osterlund, Ari Ristimaki, Markus J. Makinen, Soili Kytola, Juha Kononen, Per Pfeiffer, Leena-Maija Soveri, Mauri Keinanen, Halfdan Sorbye, Luis Nunes, Tapio Salminen, Lasse Nieminen, Aki Uutela, Paivi Halonen, Annika Algars, Jari Sundstrom, Raija Kallio, Raija Ristamaki, Annamarja Lamminmaki, Hanna Stedt, Eetu Heerva, Teijo Kuopio, Tobias Sjoblom, Helena Isoniemi, Bengt Glimelius, Pia Osterlund
Summary: BRAF-V600E mutation is a negative prognostic and predictive biomarker in metastatic colorectal cancer. Non-V600E mutations (aBRAFmt) are rare and poorly understood. This study compared the mutation patterns and characteristics of aBRAFmt with other RAS/BRAF groups in three different cohorts. The study found that aBRAFmt represents a distinct subgroup with differences in clinicopathological features, and its prognosis is slightly better than BRAF-V600E but worse than RASmt and RAS & BRAFwt. aBRAFmt should not be a contraindication for metastasectomy.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Oncology
Takayuki Yoshino, Julien Taieb, Yasutoshi Kuboki, Per Pfeiffer, Amit Kumar, Howard S. S. Hochster
Summary: This meta-analysis indicates that trifluridine/tipiracil plus bevacizumab is more effective and tolerable than trifluridine/tipiracil for refractory metastatic colorectal cancer. Despite the lack of randomized controlled trial data, the results consistently support the use of the combination therapy.
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
(2023)
Review
Oncology
Mathilde Weisz Ejlsmark, Tine Schytte, Uffe Bernchou, Rana Bahij, Britta Weber, Michael Bau Mortensen, Per Pfeiffer
Summary: Pancreatic cancer is a leading cause of cancer-related death worldwide, and the management of locally advanced or metastatic disease is difficult due to limited treatment options. While systemic chemotherapy is commonly used, the role of radiotherapy in treatment remains unclear. This review explores the available data on radiotherapy, chemoradiation, and stereotactic body radiation therapy for locally advanced pancreatic cancer. The included studies showed conflicting results and high heterogeneity, highlighting the need for further research to improve outcomes and define the role of radiation therapy in pancreatic cancer.
Article
Oncology
Eran van Veldhuisen, Sjors Klompmaker, Quisette P. Janssen, Mohammed Abu Hilal, Adnan Alseidi, Alberto Balduzzi, Gianpaolo Balzano, Claudio Bassi, Frederik Berrevoet, Morgan Bonds, Olivier R. Busch, Giovanni Butturini, Kevin C. Conlon, Isabella M. Frigerio, Giuseppe K. Fusai, Johan Gagniere, Oonagh Griffin, Thilo Hackert, Asif Halimi, Tobias Keck, Joerg Kleeff, Ulla Klaiber, Knut J. Labori, Mickael Lesurtel, Giuseppe Malleo, Marco V. Marino, I. Quintus Molenaar, Michael B. Mortensen, Andrej Nikov, Michele Pagnanelli, Rupaly Pande, Per Pfeiffer, Daniel Pietrasz, Elena Rangelova, Keith J. Roberts, Antonio Sa Cunha, Roberto Salvia, Oliver Strobel, Timo Tarvainen, Johanna W. Wilmink, Bas Groot Koerkamp, Marc G. Besselink
Summary: This study aimed to evaluate the outcome of pancreatectomy after preoperative FOLFIRINOX chemotherapy, and found that this treatment is associated with favorable outcomes for patients with BRPC and LAPC. However, the number of preoperative chemotherapy cycles and the use of adjuvant chemotherapy are not related to survival rate.
ANNALS OF SURGICAL ONCOLOGY
(2023)