Article
Oncology
R. L. Eefsen, K. S. Simonsen, P. Grundtvig, L. Klarskov, I. M. Chen, D. Hogdall, B. Jensen, T. Lorentzen, T. S. Poulsen, S. Theile, D. Nielsen, E. Hogdall
Summary: In this retrospective analysis, 90% of patients with treatment-refractory mCRC had cancer driver mutations identified through genomic sequencing, but only 2.5% of patients received targeted therapy that matched their mutations. The study highlights the challenge of limited targeted treatment options for mCRC patients with cancer driver mutations.
Article
Biology
Sun Min Lim, Eunyoung Kim, Kyung Hae Jung, Sora Kim, Ja Seung Koo, Seung Il Kim, Seho Park, Hyung Seok Park, Byoung Woo Park, Young Up Cho, Ji Ye Kim, Soonmyung Paik, Nak-Jung Kwon, Gun Min Kim, Ji Hyoung Kim, Min Hwan Kim, Min Kyung Jeon, Sangwoo Kim, Joohyuk Sohn
Summary: The study found that extreme responders to treatment for metastatic breast cancer exhibit fewer nonsynonymous mutations and CNVs. High mutational burden and visceral metastases are significantly related with disease progression.
COMMUNICATIONS BIOLOGY
(2021)
Article
Oncology
Maria Gonzalez-Gonzalez, Maria Laura Gutierrez, Jose Maria Sayagues, Luis Munoz-Bellvis, Alberto Orfao
Summary: Sporadic colorectal cancer (sCRC) is the third leading cause of cancer death in the Western world, with approximately a quarter of patients presenting metastatic dissemination at the time of diagnosis. Patients with sCRC generally have a worse prognosis compared to those with primary colorectal tumors, and there are still many genetic alterations involved in the metastatic process that need to be further identified and studied.
SEMINARS IN CANCER BIOLOGY
(2021)
Article
Oncology
Alejandra Bernardini, Marta Duenas, Maria Cruz Martin-Soberon, Carolina Rubio, Cristian Suarez-Cabrera, Raquel Ruiz-Palomares, Ester Munera-Maravilla, Sara Lazaro, Iris Lodewijk, Daniel Rueda, David Gomez-Sanchez, Teresa Alonso-Gordoa, Javier Puente, Alvaro Pinto, Pilar Gonzalez-Peramato, Carlos Aguado, Mercedes Herrera, Flora Lopez, Victor M. G. Martinez, Lucia Morales, Daniel Castellano, Jesus M. Paramio, Guillermo de Velasco
Summary: Metastatic urothelial carcinoma is a difficult-to-cure disease with limited treatment options. Vinflunine has shown some improvement in overall survival and is still used for patients who are refractory to chemotherapy and immunotherapy. However, there is a lack of biomarkers to identify responding patients and alternative therapies after treatment failure.
Article
Oncology
Arian Lundberg, Meng Zhang, Rahul Aggarwal, Haolong Li, Li Zhang, Adam Foye, Martin Sjostrom, Jonathan Chou, Kevin Chang, Thaidy Moreno-Rodriguez, Raunak Shrestha, Avi Baskin, Xiaolin Zhu, Alana S. Weinstein, Noah Younger, Joshi J. Alumkal, Tomasz M. Beer, Kim N. Chi, Christopher P. Evans, Martin Gleave, Primo N. Lara, Rob E. Reiter, Matthew B. Retting, Owen N. Witte, Alexander W. Wyatt, Felix Y. Feng, Eric J. Small, David A. Quigley
Summary: This study comprehensively characterized treatment-emergent mCRPC by integrating different sequencing techniques and found that AR-/NE- tumors were clinically and molecularly distinct with the shortest survival. In addition, the study identified CHD7 amplification and PTEN loss in these tumors, and linked elevated CHD7 expression to methylation changes in candidate enhancers. The study also revealed KLF5 as a driver of the AR-/NE- phenotype and its activity was linked to RB1 loss.
Review
Gastroenterology & Hepatology
Hideaki Bando, Atsushi Ohtsu, Takayuki Yoshino
Summary: In the era of targeted therapy based on genomic alterations, the treatment strategy for metastatic colorectal cancer (mCRC) is undergoing changes. Determining the genomic status of specific alterations such as KRAS and NRAS, BRAF(V600E) mutations, ERBB2, and microsatellite instability and/or mismatch repair (MMR) status is recommended before starting systemic treatment. Trials have shown the efficacy of pembrolizumab as first-line therapy and the combination of encorafenib and cetuximab as second-line or third-line therapy in patients with deficient MMR and BRAF(V600E) mCRC. New agents are also being developed for rare molecular fractions such as ERBB2 alterations and KRAS(G12C) mutations.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2023)
Review
Oncology
Jin Cheon Kim, Walter F. Bodmer
Summary: This study assessed the molecular pathogenesis of solid tumors, focusing specifically on colorectal cancer. Through a review of relevant literature, it was found that colorectal carcinogenesis mainly occurs through chromosomal instability, microsatellite instability, and serrated pathway. Familial colorectal cancers and genotype-phenotype correlations also play a role in colorectal carcinogenesis. The use of multi-gene panels has facilitated the detection of previously unidentified genes involved in colorectal carcinogenesis.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Seung Eun Lee, Ha Young Park, Dae-Yong Hwang, Hye Seung Han
Summary: The study revealed a high degree of genetic concordance in clinically actionable genes between primary and metastatic colorectal cancer, suggesting that genetic investigation of archived primary tumor samples could be applied in the setting of metastatic cancer precision medicine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Yujie Lu, Dingyi Gu, Chenyi Zhao, Ying Sun, Wenjing Li, Lulu He, Xiaoyan Wang, Zhongyang Kou, Jiang Su, Feng Guo
Summary: This study found that the CMS4 subtype of colorectal cancer is associated with poorer survival rates and lacks effective treatments. Through gene sequencing and expression analysis, some genes mutations and expression differences related to the CMS4 subtype were identified. The high infiltration of immune cells in this subtype suggests an immunosuppressive tumor microenvironment. These findings provide new perspectives for exploring therapeutic strategies for CMS4 subtype colorectal cancer.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Chiara Nicolazzo, Valentina Magri, Luca Marino, Francesca Belardinilli, Federica Di Nicolantonio, Gianluigi De Renzi, Salvatore Caponnetto, Michela De Meo, Giuseppe Giannini, Daniele Santini, Enrico Cortesi, Paola Gazzaniga
Summary: This study investigated the clinical and genomic features associated with RAS mutation clearance in RAS mutant mCRC patients who converted to RAS wild-type. The most commonly detected actionable mutations in neo-RAS wild-type were PIK3CA. Clearance of RAS mutations in ctDNA was associated with long-term improvement of overall survival.
FRONTIERS IN ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Bruna Calsina, Elena Pineiro-Yanez, Angel M. Martinez-Montes, Eduardo Caleiras, Angel Fernandez-Sanroman, Maria Monteagudo, Rafael Torres-Perez, Coral Fustero-Torre, Marta Pulgarin-Alfaro, Eduardo Gil, Rocio Leton, Scherezade Jimenez, Santiago Garcia-Martin, Maria Carmen Martin, Juan Maria Roldan-Romero, Javier Lanillos, Sara Mellid, Maria Santos, Alberto Diaz-Talavera, Angeles Rubio, Patricia Gonzalez, Barbara Hernando, Nicole Bechmann, Margo Dona, Maria Calatayud, Sonsoles Guadalix, Cristina Alvarez-Escola, Rita M. Regojo, Javier Aller, Maria Isabel Del Olmo-Garcia, Adria Lopez-Fernandez, Stephanie M. J. Fliedner, Elena Rapizzi, Martin Fassnacht, Felix Beuschlein, Marcus Quinkler, Rodrigo A. Toledo, Massimo Mannelli, Henri J. Timmers, Graeme Eisenhofer, Sandra Rodriguez-Perales, Orlando Dominguez, Geoffrey Macintyre, Maria Curras-Freixes, Cristina Rodriguez-Antona, Alberto Cascon, Luis J. Leandro-Garcia, Cristina Montero-Conde, Giovanna Roncador, Juan Fernando Garcia-Garcia, Karel Pacak, Fatima Al-Shahrour, Mercedes Robledo
Summary: The mechanisms of metastasis in pheochromocytoma/paraganglioma (mPPGL) are unknown. Genomic and immunogenomic profiling of mPPGL tumors reveal potential biomarkers for risk of metastasis and immunotherapy response.
NATURE COMMUNICATIONS
(2023)
Review
Oncology
Gianluca Mauri, Erica Bonazzina, Alessio Amatu, Federica Tosi, Katia Bencardino, Viviana Gori, Daniela Massihnia, Tiziana Cipani, Francesco Spina, Silvia Ghezzi, Salvatore Siena, Andrea Sartore-Bianchi
Summary: The BRAF(V600E) mutation is detected in 8-10% of patients with metastatic colorectal cancer (mCRC) and has a poor prognostic outlook, with median overall survival below 20 months. Treatment options include immune checkpoint inhibitors (CPIs) for those with concomitant MSI-H status, and a combination of cytotoxic chemotherapy + anti-VEGF or EGFR and BRAF inhibitors for first and second line treatment, respectively. However, acquired resistance limits the potential benefits and survival remains poor. Ongoing clinical trials are exploring various strategies to improve treatment outcomes for this subset of patients.
Article
Medicine, General & Internal
Ying Zuo, Jia Zhong, Hua Bai, Bin Xu, Zhijie Wang, Weihua Li, Yedan Chen, Shi Jin, Shuhang Wang, Xin Wang, Rui Wan, Jiachen Xu, Kailun Fei, Jiefei Han, Zhenlin Yang, Hua Bao, Yang Shao, Jianming Ying, Qibin Song, Jianchun Duan, Jie Wang
Summary: This study investigates the molecular characteristics of pulmonary enteric adenocarcinoma (PEAC) and lung metastatic colorectal cancer (lmCRC). The results reveal that EGFR is the key driver mutation in PEAC, while KRAS and ERBB2 are more frequently observed. In lmCRC, KRAS and APC mutations are significantly enriched. Copy number variations in certain chromosome arms were also observed between PEAC and lmCRC. Additionally, a DNA methylation-based classifier consisting of eight differentially methylated regions (DMRs) was established, providing a reliable auxiliary diagnosis for PEAC and lmCRC.
Article
Medicine, General & Internal
Ebtehal Alsolme, Saleh Alqahtani, Musa Fageeh, Duna Barakeh, Nitesh K. Sharma, Serghei Mangul, Heather A. Robinson, Amany Fathaddin, Charlotte A. E. Hauser, Malak Abedalthagafi
Summary: This study analyzed the mutation frequencies of common actionable genes in 107 Saudi Arabian patients with colorectal cancer using targeted NGS. The results showed frequent mutations in several genes, and a positive association between poorly differentiated tumors and survival rates. This preliminary analysis of molecular markers in this population can provide valuable insights into the disease progression.
Article
Genetics & Heredity
Rui Wang, Jingyun Li, Xin Zhou, Yunuo Mao, Wendong Wang, Shuai Gao, Wei Wang, Yuan Gao, Kexuan Chen, Shuntai Yu, Xinglong Wu, Lu Wen, Hao Ge, Wei Fu, Fuchou Tang
Summary: This study investigated the genomic and transcriptomic alterations in colorectal cancer (CRC) patients, revealing the prevalent activation of the PPAR signaling pathway in CRC tumors and providing insights into the origins of metastasized tumors. Additionally, the study used single-cell technology to reveal important phenotypic differences between cancer cells with and without critical point mutations. The findings offer potential markers and therapeutic targets for CRC diagnosis and therapy, as well as a rich resource for further studies.
Article
Oncology
Jeanet F. Karchoud, Anja J. Th C. M. de Kruif, Femke Lamers, Myra E. van Linde, Joyce M. Van Dodewaard-de Jong, Annemarie M. J. Braamse, Mirjam A. G. Sprangers, Aartjan T. F. Beekman, Henk M. W. Verheul, Joost Dekker
Summary: This study explores the indicators and strategies used by oncologists and nurses to determine the need for professional mental health care in cancer patients. The findings suggest that oncologists and nurses consider multiple factors, including the patient's emotional well-being and specific indicators of emotional problems, when making the decision to refer patients for professional mental health care.
JOURNAL OF CANCER SURVIVORSHIP
(2023)
Article
Gastroenterology & Hepatology
Myrtle F. Krul, Marloes A. G. Elferink, Niels F. M. Kok, Evelien Dekker, Iris Lansdorp-Vogelaar, Gerrit A. Meijer, Iris D. Nagtegaal, Emilie C. H. Breekveldt, Theo J. M. Ruers, Monique E. van Leerdam, Koert F. D. Kuhlmann
Summary: The nationwide CRC screening program in the Netherlands, started in 2014, has shown a significant reduction in the incidence of stage II and IV CRC. Patients with screen-detected CRCs had improved survival and less extensive disease compared to clinically detected cases.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Oncology
Jos B. Poell, Leon J. Wils, Arjen Brink, Ralf Dietrich, Christine Krieg, Eunike Velleuer, Ilkay Evren, Elisabeth R. Brouns, Jan G. de Visscher, Elisabeth Bloemena, Bauke Ylstra, Ruud H. Brakenhoff
Summary: This study developed a noninvasive genetic assay to detect genetically altered fields in the oral cavity. The assay demonstrated high accuracy and predicted the development of oral squamous cell carcinoma in high-risk individuals. This method can be used for cancer screening in high-risk populations and to map the extent of lesions beyond what is visible.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Hematology
Jakoba J. Eertink, Gerben J. C. Zwezerijnen, Sanne E. Wiegers, Simone Pieplenbosch, Martine E. D. Chamuleau, Pieternella J. Lugtenburg, Daphne de Jong, Bauke Ylstra, Matias Mendeville, Ulrich Duehrsen, Christine Hanoun, Andreas Huettmann, Julia Richter, Wolfram Klapper, Yvonne W. S. Jauw, Otto S. Hoekstra, Henrica C. W. de Vet, Ronald Boellaard, Josee M. Zijlstra
Summary: This study investigated whether combining clinical, molecular genotype, and radiomics features can improve the outcome prediction of patients with aggressive B-cell lymphoma. The results showed that adding radiomics features improved the model performance and positive predictive values, aiding in the identification of poor prognosis patients.
Article
Oncology
Iris van 't Erve, Jamie E. Medina, Alessandro Leal, Eniko Papp, Jillian Phallen, Vilmos Adleff, Elaine Jiayuee Chiao, Adith S. Arun, Karen Bolhuis, John K. Simmons, Aanavi Karandikar, Kenneth C. Valkenburg, Mark Sausen, Samuel Angiuoli, Robert B. Scharpf, Cornelis J. A. Punt, Gerrit A. Meijer, Victor E. Velculescu, Remond J. A. Fijneman
Summary: The study demonstrates that accurate monitoring of treatment response using ctDNA can be achieved in a tumor tissue-independent manner by combining cfDNA and patient-matched WBC genomic DNA analysis. This approach prevents false-positives caused by germline or hematopoietic variants and provides more predictive information on overall survival compared to standard radiological evaluation. Additionally, ctDNA analysis reveals potential therapy resistance mutations in a significant portion of patients.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Sanne ten Hoorn, Linda Mol, Dirkje W. Sommeijer, Lisanne Nijman, Tom van den Bosch, Tim R. de Back, Bauke Ylstra, Erik van Dijk, Carel J. M. van Noesel, Roy J. Reinten, Iris D. Nagtegaal, Miriam Koopman, Cornelis J. A. Punt, Louis Vermeulen
Summary: We evaluated the potential efficacy of adding anti-EGFR therapy to anti-VEGF therapy in a subgroup of patients with metastatic colorectal cancer. The retrospective study (CAIRO2 trial, n = 736) showed no benefit of anti-EGFR addition within the subgroup, but an overall survival increase of 6.5 months compared to the original trial.
CLINICAL COLORECTAL CANCER
(2023)
Article
Pathology
Astrid Kramer, Ed Schuuring, Daan C. L. Vessies, Paul van der Leest, Maartje J. Geerlings, Pim Rozendal, Mirthe Lanfermeijer, Theodora C. Linders, Leon C. van Kempen, Remond J. A. Fijneman, Marjolijn J. L. Ligtenberg, Gerrit A. Meijer, Daan van den Broek, Valesca P. Retel, Veerle M. H. Coup
Summary: This study developed a micro-costing framework for consistent cost calculation of ctDNA testing. The framework takes into account the complete diagnostic workflow of ctDNA testing, including costs for personnel, materials, equipment, overhead, and failures. Evaluations and case studies were performed, showing a wide range of costs per sample and the sensitivity to platform, setting, and testing volume. An open access tool is provided for laboratory-specific calculations and exploring the total costs and impact of alternative prices or assumptions.
JOURNAL OF MOLECULAR DIAGNOSTICS
(2023)
Article
Gastroenterology & Hepatology
Maarten te Groen, Lauranne A. A. P. Derikx, Lisa van Lierop, Bauke Ylstra, Frank Hoentjen, Iris D. Nagtegaal, Femke Simmer
Summary: The presence of previous colorectal neoplasia is the most significant indicator for the development of pouch neoplasia in inflammatory bowel disease. However, the underlying mechanism remains unknown. Our study found evidence of clonality between colorectal and pouch neoplasia in 30% of patients, suggesting that most pouch neoplasia develops independently from prior colorectal lesions.
INFLAMMATORY BOWEL DISEASES
(2023)
Article
Oncology
Anna Lena van Gulik, Ellen Sluydts, Liesbet Vervoort, Mark Kockx, Pim Kortman, Bauke Ylstra, Stephen P. Finn, Lukas Bubendorf, Idris Bahce, Daoud Sie, Teodora Radonic, Birgit Lissenberg-Witte, Erik Thunnissen
Summary: This study investigates the impact of cell size and ploidy on FISH results. The results show that in liver cell nuclei, the number of FISH signals increases with nuclear size and section thickness. In non-small cell lung cancer cases, tumor cells with higher ploidy levels and nuclear size have an increased chance of single signals. In addition, no rearrangements were found in lung cancer samples with borderline ALK FISH results, proving a false positive result.
TRANSLATIONAL LUNG CANCER RESEARCH
(2023)
Letter
Hematology
Wendy B. C. Stevens, G. Tjitske Los-de Vries, Carole Langois-Jacques, Andrew J. Clear, Phylicia Stathi, Birgitta Sander, Andreas Rosenwald, Maria Calaminici, Eva Hoster, Wolfgang Hiddemann, Philippe Gaulard, Gilles Salles, Wolfram Klapper, Luc Xerri, Catherine Burton, Reuben M. Tooze, Alexandra G. Smith, Christian Buske, David W. Scott, Yasodha Natkunam, Ranjana Advani, Laurie H. Sehn, John Raemaekers, John Gribben, Sandra Lockmer, Eva Kimby, Marie Jose Kersten, Delphine Maucort-Boulch, Bauke Ylstra, Erik van Dijk, Daphne de Jong
Article
Hematology
Patricia Johansson, Stefan Alig, Julia Richter, Christine Hanoun, Jan Rekowski, Jan Duerig, Bauke Ylstra, Daphne de Jong, Wolfram Klapper, Ash A. Alizadeh, Ulrich Duehrsen, Andreas Huettmann
Summary: In DLBCL, a positive interim PET scan predicts treatment failure, and combining it with the presence of an IgM gammopathy can improve prediction. The combination of interim PET and IgM gammopathy can dichotomize the population into high-risk and low-risk groups with significantly different outcomes. Only the interim PET result and IgM gammopathy status were significantly associated with outcome, making them important factors in risk-adapted treatment strategies.
ANNALS OF HEMATOLOGY
(2023)
Editorial Material
Hematology
Bauke Ylstra, Daphne de Jong
Summary: In this study, the authors demonstrate the usefulness of a dark zone signature (DZsig) for diagnosing aggressive B-cell lymphoma with DLBCL morphology, and highlight its strong prognostic value.
Article
Gastroenterology & Hepatology
Robert S. Bresalier, Carlo Senore, Graeme P. Young, James Allison, Robert Benamouzig, Sally Benton, Patrick M. M. Bossuyt, Luis Caro, Beatriz Carvalho, Han-Mo Chiu, Veerle M. H. Coupe, Willemijn de Klaver, Clasine Maria de Klerk, Evelien Dekker, Sunil Dolwani, Callum G. Fraser, William Grady, Lydia Guittet, Samir Gupta, Stephen P. Halloran, Ulrike Haug, Geir Hoff, Steven Itzkowitz, Tim Kortlever, Anastasios Koulaouzidis, Uri Ladabaum, Beatrice Lauby-Secretan, Marcis Leja, Bernard Levin, Theodore Robert Levin, Finlay Macrae, Gerrit A. Meijer, Joshua Melson, Colm O'Morain, Susan Parry, Linda Rabeneck, David F. Ransohoff, Roque Saenz, Hiroshi Saito, Silvia Sanduleanu-Dascalescu, Robert E. Schoen, Kevin Selby, Harminder Singh, Robert J. C. Steele, Joseph J. Y. Sung, Erin Leigh Symonds, Sidney J. Winawer
Summary: New non-invasive tests for colorectal cancer (CRC) are emerging, making it challenging to conduct trials with mortality reduction as the main goal. A formal consensus approach involving experts resulted in the revision of previously established principles and the emergence of twelve new principles. The effectiveness of a new test can be evaluated by comparing it with an established non-invasive test, with the faecal immunochemical test considered as the appropriate comparator. Flexible adjustment of the new test's positivity threshold is desirable to meet different screening goals and requirements. A four-phased approach is proposed for the evaluation of new tests, including small studies, prospective estimation of accuracy, evaluation in screening populations, and monitoring for missed lesions.
Article
Pathology
Tanya T. D. Soeratram, Hedde D. Biesma, Jacqueline M. P. Egthuijsen, Elma Meershoek-Klein Kranenbarg, Henk H. Hartgrink, Cornelis J. H. van de Velde, Aart Mookhoek, Erik van Dijk, Yongsoo Kim, Bauke Ylstra, Hanneke W. M. van Laarhoven, Nicole C. T. van Grieken
Summary: Tumor-infiltrating lymphocytes are important for the survival of gastric cancer patients, and T-cell densities in different regions of the tumor can serve as prognostic markers. CD8OIM and FOXP3TC are identified as key factors for survival, and the combination of their densities can stratify patients into distinct subgroups with different prognosis. These immune subgroups are independent predictors for cancer-specific survival in resectable gastric cancer.
Article
Multidisciplinary Sciences
Margaretha G. M. Roemer, Tim van de Brug, Erik Bosch, Daniella Berry, Nathalie Hijmering, Phylicia Stathi, Karin Weijers, Jeannette Doorduijn, Jacoline Bromberg, Mark van de Wiel, Bauke Ylstra, Daphne de Jong, Yongsoo Kim
Summary: In order to understand the clinical relevance of the tumor microenvironment (TME), it is important to study the interactions between malignant and non-malignant cells in clinical samples. Researchers have developed a computational framework to comprehensively analyze the spatial context of the TME, including close and long-distance interactions between different cell types. This framework was applied to imaging data from 88 primary central nervous system lymphomas, revealing significant prognostic subgroups mainly determined by the spatial context. The results highlight the importance of spatial context in predicting patient survival, particularly in relation to macrophage infiltration near specific cell types.
