Review
Cell Biology
Diamantis I. Tsilimigras, Ioannis Ntanasis-Stathopoulos, Timothy M. Pawlik
Summary: The liver is a common site for metastasis in colorectal cancer patients due to the direct connection between the colon and rectum and the liver through the portal vein circulation. The liver tumor microenvironment consists of different cell types that modulate antigen recognition and immune system activation. Primary tumors from other sites create a pre-metastatic niche in the liver before the seeding of cancer cells. There are four key phases in the development of liver metastases: microvascular infiltration, extravascular pre-angiogenesis, angiogenesis, and tumor growth.
Review
Gastroenterology & Hepatology
Raphael L. C. Araujo, Leonardo G. Fonseca, Raphael Oliveira Silva, Marcelo Moura Linhares, Pedro L. S. Uson Junior
Summary: Colorectal cancer is the third most common cancer, with about 20% of cases diagnosed with synchronous metastatic disease. Surgery is still the main treatment for resectable colorectal liver metastases, but the optimal timing for neoadjuvant chemotherapy or upfront surgery has not been established. Patient selection based on imaging, recurrence time, positive lymph nodes, and molecular biomarkers can improve decision-making. Molecular profiling is rising as a promising field to guide patient selection and treatment sequencing. This review discusses the role of molecular pathology and biomarkers in the diagnosis and treatment of resectable colorectal liver metastases.
HEPATOBILIARY SURGERY AND NUTRITION
(2023)
Article
Oncology
Qi Lin, Kefeng Ding, Ren Zhao, Hao Wang, Ye Wei, Li Ren, Qinghai Ye, Yuehong Cui, Guodong He, Wentao Tang, Qingyang Feng, Dexiang Zhu, Wenju Chang, Xiaoying Wang, Li Liang, Guofeng Zhou, Fei Liang, Feng Ye, Jianwei Wang, Jia Fan, Jianmin Xu
Summary: This study suggests that pre-PTR chemotherapy can improve progression-free survival for patients with asymptomatic synchronous unresectable CRLMs, while also improving disease control rate.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Medicine, Research & Experimental
Ambre Giguelay, Evgenia Turtoi, Lakhdar Khelaf, Guillaume Tosato, Ikrame Dadi, Tommy Chastel, Marie-Alix Poul, Marine Pratlong, Stefan Nicolescu, Dany Severac, Antoine Adenis, Olivia Sgarbura-Popescu, Sebastien Carrere, Philippe Rouanet, Marc Ychou, Francois Quenet, Didier Pourqier, Pierre-Emmanuel Colombo, Andrei Turtoi, Jacques Colinge
Summary: This study confirms the heterogeneity of CRC-LM CAFs through single-cell transcriptomic analysis and proposes a model for recruiting different origins of CAFs to the liver in different liver malignancies. Additionally, the study finds that targeting LTBP2 with antibodies may help deplete ECM-remodeling CAFs in CRC-LMs.
Article
Oncology
David Henault, David Stephen, Pierre-Antoine St-Hilaire, Nouredin Messaoudi, Franck Vandenbroucke-Menu, Eve Simoneau, Zhixia Rong, Marylene Plasse, Richard Letourneau, Andre Roy, Michel Dagenais, Real Lapointe, Bich Nguyen, Anne-Marie Mes-Masson, G. Soucy, Simon Turcotte
Summary: The density of tumor-infiltrating lymphocytes, the expression of class I major histocompatibility complex (MHC-I), and the pathological response to preoperative chemotherapy were shown to be associated with oncological outcomes in colorectal cancer liver metastases (CRLM) after complete resection. However, the significance of heterogeneity in these features for multiple CRLMs is still under investigation. Our study found that patients with immune homogeneous CRLMs had longer time to recurrence and better disease-specific survival compared to those with heterogeneous CRLMs. Homogeneity of response to preoperative chemotherapy was not associated with oncological outcomes. The heterogeneity of CD3 and MHC-I expression was independent of response to chemotherapy and other clinicopathological variables.
Review
Biochemistry & Molecular Biology
Daniel-Clement Osei-Bordom, Sivesh Kamarajah, Niki Christou
Summary: In the clinical management of liver metastasis of colorectal cancer, surgeons and oncologists categorize the metastasis into resectable and non-resectable groups to initiate tailored therapeutics. The combination of targeted therapies and biotherapies around these two entities is being actively explored to determine the ideal conditions for their application to improve patient survival and quality of life.
Article
Multidisciplinary Sciences
William W. Ho, Igor L. Gomes-Santos, Shuichi Aoki, Meenal Datta, Kosuke Kawaguchi, Nilesh P. Talele, Sylvie Roberge, Jun Ren, Hao Liu, Ivy X. Chen, Patrik Andersson, Sampurna Chatterjee, Ashwin S. Kumar, Zohreh Amoozgar, Qixian Zhang, Peigen Huang, Mei Rosa Ng, Vikash P. Chauhan, Lei Xu, Dan G. Duda, Jeffrey W. Clark, Mikael J. Pittet, Dai Fukumura, Rakesh K. Jain
Summary: Liver metastasis of mismatch repair-proficient (pMMR) CRCs is unresponsive to immune checkpoint blockade (ICB) therapy, while the same tumors are sensitive to ICB therapy when grown subcutaneously. Dendritic cells play a crucial role in increasing the efficacy of immuno-therapies against pMMR CRC liver metastases, as evidenced by increased infiltration and improved survival in mouse models. Compared to subcutaneous tumors, orthotopic liver metastases of pMMR CRCs show a paucity of activated T cells and dendritic cells, indicating the importance of utilizing orthotopic tumor models in guiding human clinical trials.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Mary F. Mulcahy, Armeen Mahvash, Marc Pracht, Amir H. Montazeri, Steve Bandula, Robert C. G. Martin, Ken Herrmann, Ewan Brown, Darryl Zuckerman, Gregory Wilson, Tae-You Kim, Andrew Weaver, Paul Ross, William P. Harris, Janet Graham, Jamie Mills, Alfonso Yubero Esteban, Matthew S. Johnson, Constantinos T. Sofocleous, Siddharth A. Padia, Robert J. Lewandowski, Etienne Garin, Philip Sinclair, Riad Salem
Summary: The study demonstrates that the addition of TARE to second-line chemotherapy for CLM patients results in longer progression-free survival and hepatic progression-free survival, with an improved objective response rate. However, there was no significant difference in overall survival between the two groups, and the rate of grade 3 adverse events was higher in the TARE group. Further subset analyses are needed to identify the ideal patient population for TARE benefit.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Yuan -Mao Lin, Iwan Paolucci, Caleb S. O'Connor, Brian M. Anderson, Bastien Rigaud, Bryan M. Fellman, Kyle A. Jones, Kristy K. Brock, Bruno C. Odisio
Summary: This study evaluated a biomechanical deformable image registration method for quantifying the minimal ablative margin (MAM) in three dimensions and its association with local disease progression following CT-guided colorectal liver metastasis (CLM) ablation. The results showed that a MAM of 0 mm was associated with a high risk of local disease progression, while a MAM greater than or equal to 5 mm had a lower risk.
Article
Surgery
Kosuke Kobayashi, Yosuke Inoue, Yuki Kitano, Shoki Sato, Atsushi Oba, Yoshihiro Ono, Takafumi Sato, Hiromichi Ito, Yoshihiro Mise, Akio Saiura, Yu Takahashi
Summary: A predictive model for conversion surgery was developed and the long-term outcomes of patients with technically unresectable colorectal liver metastases were evaluated. Patients who underwent conversion surgery had significantly higher median overall survival compared to those who did not. The predictive model for conversion surgery was constructed using several predictive factors. Patients were graded according to their scores, and those in Grade A had significantly better overall survival than Grade B and C patients.
Article
Surgery
Mushegh A. Sahakyan, Kristoffer Watten Brudvik, Jon-Helge Angelsen, Rachel G. Dille-Amdam, Oddvar M. Sandvik, Bjorn Edwin, Linn S. Nymo, Kristoffer Lassen
Summary: This study aimed to investigate the association between selected preoperative inflammatory markers and outcomes of liver resection for colorectal liver metastases (CRLM). It was found that Glasgow prognostic score (GPS), modified Glasgow prognostic score (mGPS), and C-reactive protein to albumin ratio (CAR) had no impact on postoperative complications, but CAR was a better predictor of overall survival, especially after open liver resections.
WORLD JOURNAL OF SURGERY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Sam Eriksson, Johan Bengtsson, William Toren, Jimmy Latt, Roland Andersson, Christian Sturesson
Summary: Among patients with CRLMs undergoing preoperative chemotherapy, changes in lesion ADCs were found to not distinguish between pathological responding and non-responding lesions.
Review
Oncology
Alexandra Nassar, Stylianos Tzedakis, Alix Dhote, Marie Strigalev, Romain Coriat, Mehdi Karoui, Anthony Dohan, Martin Gaillard, Ugo Marchese, David Fuks
Summary: This literature review aimed to assess the feasibility of laparoscopic liver resection for multiple colorectal liver metastases. The minimally invasive approach for liver cancer has become a new standard of oncological care, and laparoscopic liver resection is a significant indication for multiple colorectal liver metastases. The purpose of this paper was to highlight the novelty and updates in the field of multiple minimally invasive liver resections and discuss the feasibility and outcomes of laparoscopic concomitant multiple liver resections for colorectal liver metastases.
Article
Oncology
Lily V. Saadat, Thomas Boerner, Debra A. Goldman, Mithat Gonen, Timothy L. Frankel, Efsevia Vakiani, T. Peter Kingham, William R. Jarnagin, Alice C. Wei, Kevin C. Soares, David B. Solit, Michael I. D'Angelica
Summary: RAS mutations are prognostic for mCRC patients. KRAS exon 3/4 mutations are rare and may be associated with a more favorable prognosis, but the difference in oncologic outcomes based on the mutated exon appears to be smaller than previously reported.
ANNALS OF SURGICAL ONCOLOGY
(2021)
Article
Immunology
Mingtao Hu, Zhigang Chen, Dandan Hu, Shaoyan Xi, Deshen Wang, Xiaolong Zhang, William Pat Fong, Lei Wen, Yanyu Cai, Yunfei Yuan, Binkui Li, Xiaojun Wu, Zhenhai Lu, Gong Chen, Liren Li, Peirong Ding, Zhizhong Pan, Desen Wan, Ziming Du, Minshan Chen, Yuhong Li
Summary: The study found that HGPs of colorectal cancer liver metastases have distinct molecular characteristics and are enriched in different signaling pathways. The morphological changes of HGPs are the combined effect of the heterogeneity and remodeling of primary tumors seeds and liver soils.
FRONTIERS IN IMMUNOLOGY
(2022)
Meeting Abstract
Oncology
Van K. Morris, Greg Yothers, Scott Kopetz, Samuel A. Jacobs, Peter C. Lucas, Atif Iqbal, Patrick M. Boland, Dustin A. Deming, Aaron James Scott, Howard John Lim, Theodore S. Hong, Norman Wolmark, Thomas J. Georgenrg
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Arvind Dasari, Maen Abdelrahim, Jared David Acoba, Krishna Chaitanya Alluri, Tomislav Dragovich, Syed Mohammad Ali Kazmi, Benjamin Leon Musher, Ryan Sun, Lucas Wong, Y. Nancy You, Robert Anthony Zaiden, Scott Kopetz
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Maliha Nusrat, Muddassir Ali Syed, Riham Katkhuda, Edwin R. Parra, Ignacio Ivan Wistuba, Paul Kong, Amanda Koehne, Arvind Dasari, Michael J. Overman, David Menter, Scott Kopetz
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Michael Sangmin Lee, Tyler J. Zemla, Kristen Keon Ciombor, Autumn Jackson Mcree, Mehmet Akce, Shaker R. Dakhil, Brandy L. Jaszewski, Fang-Shu Ou, Tanios S. Bekaii-Saab, Scott Kopetz
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Gastroenterology & Hepatology
Nicky van der Heijde, Frederique L. Vissers, Alberto Manzoni, Giuseppe Zimmitti, Joaquim Balsells, Frederik Berrevoet, Bergthor Bjornsson, Peter van den Boezem, Ugo Boggi, Svein O. Bratlie, Fernando Burdio, Andrea Coratti, Mathieu D'Hondt, Carlos D. Del Pozo, Safi Dokmak, Regis Fara, Mehmet F. Can, Sebastiaan Festen, Antonello Forgione, Claus Fristrup, Sebastien Gaujoux, Bas Groot Koerkamp, Thilo Hackert, Igor E. Khatkov, Tobias Keck, Hanna Seppanen, Daan Lips, Misha Luyer, Gabriella Pittau, Manuel Maglione, I. Quintus Molenaar, Patrick Pessaux, Geert Roeyen, Olivier St-Marc, Santiago S. Cabus, Hjalmar van Santvoort, George van der Schelling, Mario Serradilla-Martin, Francois-regis Souche, Miguel A. Suarez Munoz, Marco Marino, Marc G. Besselink, Mohammed Abu Hilal
Summary: The E-MIPS registry collects data on laparoscopic and robotic minimally invasive pancreatic surgery (MIPS) across Europe. This study analyzed the first year of the registry and found that MIDP was performed in about half of the patients, mainly using laparoscopy, while MIPD was performed in about a quarter of the patients, more often using the robotic approach. There were only a minority of centers that met the Miami guideline volume criteria for MIPD.
Article
Oncology
Kanwal Raghav, Fang-Shu Ou, Alan P. Venook, Federico Innocenti, Ryan Sun, Heinz-Josef Lenz, Scott Kopetz
Summary: Clinical trial updates allow for dissemination of additional results from studies where the primary end point has already been reported. This study aimed to determine the prevalence of acquired genomic alterations (Acq-GAs) on anti-EGFR-chemotherapy compared to anti-VEGF-chemotherapy and later-line anti-EGFR-antibody therapy in metastatic colorectal cancer (mCRC). The findings indicate divergent resistance mechanisms with rare occurrence of Acq-GAs with up-front use of anti-EGFR-chemotherapy.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Editorial Material
Oncology
Veronika Fedirko, Scott Kopetz, Carrie R. Daniel
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Editorial Material
Oncology
Madhulika Eluri, Scott Kopetz, Christine M. Parseghian
Summary: The use of serial ctDNA in metastatic colorectal cancer has the potential to refine patient selection, reduce chemotherapy toxicity, and assess emerging resistance mechanisms for novel therapeutic strategies. However, important questions remain regarding its validation as a predictive biomarker of treatment response.
CLINICAL CANCER RESEARCH
(2023)
Letter
Oncology
Kanwal Raghav, Scott Kopetz, Ying Yuan
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Blessie Elizabeth Nelson, Apostolia M. Tsimberidou, Xueyao Fu, Siqing Fu, Vivek Subbiah, Anil K. Sood, Jordi Rodon, Daniel D. Karp, George Blumenschein, Scott Kopetz, Shubham Pant, Sarina A. Piha-Paul
Summary: This study evaluated the combination of bevacizumab, temsirolimus, and valproic acid in patients with advanced malignancies and found modest efficacy but significant toxicity. The study is the first to evaluate this combination and suggests potential for anticancer activity, but careful management of toxicity is necessary for future development.
Article
Oncology
Rebecca Thonhauser, Marcus Poglitsch, Jan Philipp Jonas, Yawen Dong, Madita Tschoegl, Mariel Gramberger, Mohamed Salem, Jonas Santol, Irmgard Brandl, Martin Klimpfinger, Constantin Vierziger, Thomas Gruenberger
Summary: This study compared the use of VEGF and EGFR antibodies in the treatment of synchronous metastasized colorectal cancer patients. The results showed that patients treated with VEGF antibodies had a better pathological response of the primary tumor and longer recurrence-free survival compared to those treated with EGFR antibodies. There was no difference in overall survival.
Article
Oncology
Tijs J. Hoogteijling, Jasper P. Sijberden, John N. Primrose, Victoria Morrison-Jones, Sachin Modi, Giuseppe Zimmitti, Marco Garatti, Claudio Sallemi, Mario Morone, Mohammad Abu Hilal
Summary: This study evaluated the safety and feasibility of Laparoscopic right hemihepatectomy (L-RHH) after Future liver remnant modulation (FLRM), compared to ex novo L-RHH. The results showed that L-RHH after FLRM is more technically complex, with longer operative time and Pringle duration, but it remains safe and feasible in experienced hands.
Article
Oncology
Kyaw Z. Thein, Amadeo B. Biter, Kimberly C. Banks, Andrew W. Duda, Jennifer Saam, Jason Roszik, Filip Janku, Ferdinandos Skoulidis, John V. Heymach, Scott Kopetz, Funda Meric-Bernstam, David S. Hong
Summary: This study conducted a comprehensive analysis of KRAS(G12C) mutations in different types of cancer through liquid biopsy. The results showed that KRAS(G12C) mutations were detected in various cancers, with the highest detection rate in lung cancer.
JCO PRECISION ONCOLOGY
(2022)
Letter
Oncology
Pashtoon M. Kasi, Gordon Fehringer, Alexey Aleshin, Scott Kopetz
JCO PRECISION ONCOLOGY
(2022)
Article
Surgery
Anai Kothari, Michael G. White, Oliver Peacock, Harmeet Kaur, Sarah M. Palmquist, Nancy You, Melissa Taggart, Usama Salem, Michael Overman, Scott Kopetz, George J. Chang
Summary: This case series demonstrates the excellent pathological response to neoadjuvant checkpoint inhibitor therapy in colorectal cancer patients with mismatch repair deficiency, resulting in exemplary short-term oncological outcomes. It also opens up possibilities for future studies on limited resection in patients who would otherwise require multivisceral resection.
BRITISH JOURNAL OF SURGERY
(2022)