Article
Oncology
Oliver J. Ott, Cihan Gani, Lars H. Lindner, Manfred Schmidt, Ulf Lamprecht, Sultan Abdel-Rahman, Axel Hinke, Thomas Weissmann, Arndt Hartmann, Rolf D. Issels, Daniel Zips, Claus Belka, Robert Grutzmann, Rainer Fietkau
Summary: The HyRec trial evaluated an intensified neoadjuvant and multimodality treatment schedule for locally recurrent rectal cancer patients, showing promising efficacy and high feasibility, with comparable toxicities and very high pathologically confirmed complete remission rates.
Article
Gastroenterology & Hepatology
Palash Asawa, Veli Bakalov, Pragnan Kancharla, Stephen Abel, Zena Chahine, Dulabh K. Monga, Alexander Kirichenko, Rodney E. Wegner
Summary: Through analysis of the National Cancer Database, we found that KRAS mutation is associated with prognosis in patients with locally advanced rectal cancer, with KRAS-positive patients having poorer survival.
INTERNATIONAL JOURNAL OF COLORECTAL DISEASE
(2022)
Review
Immunology
Yaqi Wang, Lijun Shen, Juefeng Wan, Hui Zhang, Ruiyan Wu, Jingwen Wang, Yan Wang, Ye Xu, Sanjun Cai, Zhen Zhang, Fan Xia
Summary: For patients with locally advanced rectal cancer, neoadjuvant chemoradiotherapy followed by total mesorectal excision is the standard treatment, which can reduce local recurrence rate and improve tumor response. The combination of radiotherapy and immunotherapy has a strong theoretical basis and ongoing clinical trials are showing promising short-term efficacy. Accurately evaluating the treatment response after neoadjuvant therapy is important for patient selection of the 'Watch and Wait' approach. Finding accurate biomarkers can help guide treatment decisions and large-scale clinical trials are needed to explore long-term prognosis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Peige Zhou, Paolo Goffredo, Timothy Ginader, Dakota Thompson, Jennifer Hrabe, Irena Gribovskaja-Rupp, Muneera Kapadia, Imran Hassan
Summary: In locally advanced rectal cancer patients, mKRAS was not associated with lower pCR rates or NAR scores, but it was independently associated with worse survival.
JOURNAL OF SURGICAL ONCOLOGY
(2021)
Review
Oncology
Huaqin Lin, Lei Wang, Xiaohong Zhong, Xueqing Zhang, Lingdong Shao, Junxin Wu
Summary: This meta-analysis comparing neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACRT) for locally advanced rectal cancer (LARC) found that NAC was superior to NACRT in terms of sphincter preservation rate, but noninferior in terms of other outcomes. Further validation is needed for these conclusions.
WORLD JOURNAL OF SURGICAL ONCOLOGY
(2021)
Article
Oncology
Francesca De Felice, Vincenzo Tombolini, Enrico Cortesi
Summary: Locally advanced rectal cancer requires a multidisciplinary management involving neoadjuvant radiotherapy, conservative surgery, and chemotherapy. Recent studies have examined the potential benefits of altering the sequencing or intensity of the standard trimodal therapy components, with a focus on the clinical significance of total neoadjuvant treatment. More long-term results and prospective studies are needed to accurately determine the clinical benefits and establish the role of total neoadjuvant therapy in locally advanced rectal cancer.
TRANSLATIONAL ONCOLOGY
(2021)
Review
Oncology
Zhen Yu, Yuying Hao, Yuhua Huang, Ling Ling, Xigang Hu, Simiao Qiao
Summary: Radiotherapy and chemotherapy are effective treatments for locally advanced rectal cancer. New neoadjuvant treatment options need to be explored for better outcomes. Targeted drugs and immunologic agents have shown efficacy in advanced rectal cancer but have not been commonly used in neoadjuvant therapy for LARC patients.
FRONTIERS IN ONCOLOGY
(2023)
Review
Oncology
Ryota Mori, Mamoru Uemura, Yuki Sekido, Tsuyoshi Hata, Takayuki Ogino, Hidekazu Takahashi, Norikatsu Miyoshi, Tsunekazu Mizushima, Yuichiro Doki, Hidetoshi Eguchi
Summary: This case report presents a patient with locally advanced rectal cancer who achieved pathological complete response and complete radical resection through total neoadjuvant therapy (TNT) with the addition of nivolumab. The results suggest that nivolumab in combination with TNT can be an effective preoperative strategy for rectal cancer patients with high levels of microsatellite instability.
WORLD JOURNAL OF SURGICAL ONCOLOGY
(2022)
Article
Oncology
Incheol Seo, Hye Won Lee, Sang Jun Byun, Jee Young Park, Hyeonji Min, Sung Hwan Lee, Ju-Seog Lee, Shin Kim, Sung Uk Bae
Summary: The study found that neoadjuvant chemoradiation therapy (CRT) significantly enriched the immune response in locally advanced rectal cancer (LARC) tissues and affected related immunogenic effects. Furthermore, CRT can lead to downregulation of MMR system-related genes and an increase in tumor mutational burden and proportions of immune-related cells in LARC tissues.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Xinyu Shi, Min Zhao, Bo Shi, Guoliang Chen, Huihui Yao, Junjie Chen, Daiwei Wan, Wen Gu, Songbing He
Summary: This study found that pretreatment blood biomarkers combined with MRI can better predict the efficacy of NCRT in patients with locally advanced rectal cancer. By analyzing pretreatment blood biomarkers and MRI-related data, the possibility of pathological complete response to NCRT can be assessed in advance, which helps guide clinical decisions and treatment plans.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Valentina Dapra, Marco Airoldi, Michela Bartolini, Roberta Fazio, Giuseppe Mondello, Maria Chiara Tronconi, Maria Giuseppina Prete, Giuseppe D'Agostino, Caterina Foppa, Antonino Spinelli, Alberto Puccini, Armando Santoro
Summary: Recently, there has been a significant shift in the therapeutic landscape of locally advanced rectal cancer (LARC) with the increasing adoption of total neoadjuvant treatment (TNT). This comprehensive approach involves administering chemotherapy and radiation therapy prior to surgery, followed by optional adjuvant chemotherapy. To provide the optimal tailored treatment regimen for patients, collaboration among healthcare professionals from various specialties is crucial. This review aims to provide insights into the current state of TNT for LARC and emerging strategies for future research and clinical practice, such as circulating tumor DNA, immunotherapy in mismatch repair-deficient tumors, and nonoperative management.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Shanshan Lian, Huiming Liu, Tiebao Meng, Lidi Ma, Weilong Zeng, Chuanmiao Xie
Summary: This study found that the synthetic MRI-derived T1 relaxation time and T2 relaxation time values are promising imaging markers for predicting a good response to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer.
EUROPEAN RADIOLOGY
(2023)
Article
Oncology
Jingjing Wu, Mingzhe Huang, Yuanhui Wu, Yisong Hong, Linbin Cai, Rongzhao He, Yanxin Luo, Puning Wang, Meijin Huang, Jinxin Lin
Summary: This study compared the therapeutic outcomes and survival rates of locally advanced rectal cancer patients who received neoadjuvant chemotherapy (N-CT) or neoadjuvant chemoradiotherapy (N-CRT). The results showed that although N-CT caused fewer complications, there was no significant difference in survival rates compared to N-CRT. Therefore, N-CT could be considered as an alternative treatment for rectal cancer.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Oncology
Daniela Rega, Vincenza Granata, Antonella Petrillo, Ugo Pace, Cinzia Sassaroli, Massimiliano Di Marzo, Carmela Cervone, Roberta Fusco, Valeria D'Alessio, Guglielmo Nasti, Carmela Romano, Antonio Avallone, Biagio Pecori, Gerardo Botti, Fabiana Tatangelo, Piera Maiolino, Paolo Delrio
Summary: This Phase II randomized controlled trial investigates whether using Electrochemotherapy (ECT) before surgery in patients with major clinical response after neoadjuvant therapy allows for a more conservative surgical approach in Locally Advanced Rectal Cancer (LARC). The study aims to evaluate the increase of complete response rate after neoadjuvant treatment and spare organ function due to TME, by assessing treatment response using histopathological tumor regression grade on tissue specimens.
Review
Immunology
Weiwei Xiao, Huilong Luo, Ye Yao, Yaqin Wang, Shuang Liu, Rui Sun, Gong Chen
Summary: Total neoadjuvant treatment (TNT) is highly effective for local advanced rectal cancer (LARC), improving complete response rate, reducing distant metastasis risk, and increasing sphincter preservation rate. It is also beneficial for distant rectal cancer patients who want organ preservation. Combining neoadjuvant chemoradiotherapy (NACRT) with programmed cell death-1 (PD-1)/PD-L1 antibodies seems to offer promising results for mismatch repair proficient (pMMR)/microsatellite stable (MSS) LARC patients, although the ideal total dose and fractionation of radiotherapy in this combination setting remain unresolved.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Gastroenterology & Hepatology
Jonathan B. Yuval, Hannah M. Thompson, Megan Fiasconaro, Sujata Patil, Iris H. Wei, Emmanouil P. Pappou, J. Joshua Smith, Jose G. Guillem, Garrett M. Nash, Martin R. Weiser, Philip B. Paty, Julio Garcia-Aguilar, Maria Widmar
Summary: This study evaluates the relationship between tumor and anatomical features with operative difficulty in robotic low anterior resection. The results suggest that factors such as gender, body mass index, neoadjuvant radiotherapy, tumor height, sacral height, and mesorectal area are associated with longer operating time.
COLORECTAL DISEASE
(2022)
Article
Oncology
Seo-Hyun Choi, Jin K. Kim, Chin-Tung Chen, Chao Wu, Michael R. Marco, Francisco M. Barriga, Kevin O'Rourke, Raphael Pelossof, Xuan Qu, Qing Chang, Elisa de Stanchina, Jinru Shia, J. Joshua Smith, Francisco Sanchez-Vega, Julio Garcia-Aguilar
Summary: KRAS-mutant colorectal cancer upregulates integrin a6/b4 to promote aggressive tumor behavior and lung metastasis, while knocking out ITGB4 diminishes these features and reduces pulmonary metastasis.
MOLECULAR CANCER RESEARCH
(2022)
Article
Multidisciplinary Sciences
Chun Chou, Xian Zhang, Chirag Krishna, Briana G. Nixon, Saida Dadi, Kristelle J. Capistrano, Emily R. Kansler, Miranda Steele, Jian Han, Amy Shyu, Jing Zhang, Efstathios G. Stamatiades, Ming Liu, Shun Li, Mytrang H. Do, Chaucie Edwards, Davina S. Kang, Chin-Tung Chen, Iris H. Wei, Emmanouil P. Pappou, Martin R. Weiser, J. Garcia-Aguilar, J. Joshua Smith, Christina S. Leslie, Ming O. Li
Summary: A new class of tumor-infiltrating T cells (ILTCKs) has been identified, which are alpha beta T cell receptor (TCR)-positive and express FCER1G, with high cytotoxic potential. ILTCKs react broadly to unmutated self-antigens, arise from distinct thymic progenitors following early encounter with cognate antigens, and are continuously replenished by thymic progenitors during tumor progression. ILTCKs' expansion and effector differentiation depend on interleukin-15 (IL-15) expression in cancer cells, and inducible activation of IL-15 signaling suppresses tumor growth. This distinguishes ILTCKs from conventional cytotoxic T cells.
Article
Oncology
Jin K. Kim, Michael R. Marco, Campbell S. D. Roxburgh, Chin-Tung Chen, Andrea Cercek, Paul Strombom, Larissa K. F. Temple, Garrett M. Nash, Jose G. Guillem, Philip B. Paty, Rona Yaeger, Zsofia K. Stadler, Mithat Gonen, Neil H. Segal, Diane L. Reidy, Anna Varghese, Jinru Shia, Efsevia Vakiani, Abraham J. Wu, Paul B. Romesser, Christopher H. Crane, Marc J. Gollub, Leonard Saltz, J. Joshua Smith, Martin R. Weiser, Sujata Patil, Julio Garcia-Aguilar
Summary: While TNT does not significantly prolong survival compared to neoadjuvant chemoradiotherapy with intended postoperative chemotherapy, it does show a higher complete response rate in LARC patients, potentially allowing more patients to preserve their rectum.
Article
Oncology
Jin K. Kim, Chin-Tung Chen, Ajaratu Keshinro, Asama Khan, Canan Firat, Chad Vanderbilt, Neil Segal, Zsofia Stadler, Jinru Shia, Vinod P. Balachandran, Martin R. Weiser
Summary: T cells in colon tumors with deficient DNA mismatch repair (dMMR) are more clonal and have a less diverse repertoire compared to tumors with proficient mismatch repair (pMMR). This suggests that T cells clonally expand in response to MMR deficiency-induced tumor neoantigens in dMMR tumors.
Article
Anesthesiology
Jonathan B. Yuval, Jasme Lee, Fan Wu, Hannah M. Thompson, Floris S. Verheij, Hersh Gupta, Takeshi Irie, Joseph R. Scarpa, Patrick J. McCormick, J. Joshua Smith, Jinru Shia, Martin R. Weiser, Francisco Sanchez-Vega, Kay See Tan, Gregory W. Fischer, Julio Garcia-Aguilar, Joshua S. Mincer
Summary: Intraoperative opioid exposure is associated with immunomodulation in colon adenocarcinoma. Higher opioid dose is associated with lower tumor recurrence risk, especially in tumors with DNA MMR deficiency.
BRITISH JOURNAL OF ANAESTHESIA
(2022)
Article
Gastroenterology & Hepatology
Ajaratu Keshinro, Karuna Ganesh, Chad Vanderbilt, Canan Firat, Jin K. K. Kim, Chin-Tung Chen, Rona Yaeger, Neil H. H. Segal, Mithat Gonen, Jinru Shia, Zsofia K. K. Stadler, Martin R. R. Weiser
Summary: This study aimed to determine the influence of mismatch repair loss on the molecular and clinicopathological features of microsatellite instability-high colon cancer. Different types of mismatch repair loss were found, including hypermethylation of the MLH1 promoter, biallelic inactivation, constitutional pathogenic variants, and loss of specific mismatch repair proteins. The type of mismatch repair loss affects tumor mutational burden, tumor-infiltrating lymphocytes, microsatellite instability, and other characteristics.
DISEASES OF THE COLON & RECTUM
(2023)
Article
Biochemistry & Molecular Biology
Walid K. Chatila, Jin K. Kim, Henry Walch, Michael R. Marco, Chin-Tung Chen, Fan Wu, Dana M. Omer, Danny N. Khalil, Karuna Ganesh, Xuan Qu, Anisha Luthra, Seo-Hyun Choi, Yu-Jui Ho, Ritika Kundra, Katharine I. Groves, Oliver S. Chow, Andrea Cercek, Martin R. Weiser, Maria Widmar, Iris H. Wei, Emmanouil P. Pappou, Garrett M. Nash, Philip B. Paty, Qian Shi, Efsevia Vakiani, S. Duygu Selcuklu, Mark T. A. Donoghue, David B. Solit, Michael F. Berger, Jinru Shia, Raphael Pelossof, Paul B. Romesser, Rona Yaeger, J. Joshua Smith, Nikolaus Schultz, Francisco Sanchez-Vega, Julio Garcia-Aguilar
Summary: The incidence of rectal cancer is increasing in younger patients. Neoadjuvant therapy can avoid surgery, but determining response-related factors is important. APC mutations are associated with aggressive behavior, KRAS mutations with increased risk of relapse, and overexpression of IGF2 and L1CAM with decreased treatment response. In addition, RNA-sequencing can identify immune hot tumors with better response to neoadjuvant therapy. DNA and RNA sequencing can serve as biomarkers for treatment response in rectal cancer patients, informing non-operative treatment strategies.
Article
Oncology
Brian D. Griffith, Simon Turcotte, Jenny Lazarus, Fatima Lima, Samantha Bell, Lawrence Delrosario, Jake McGue, Santhoshi Krishnan, Morgan D. Oneka, Hari Nathan, J. Joshua Smith, Michael D'Angelica, Jinru Shia, Marina Pasca Di Magliano, Arvind Rao, Timothy L. Frankel
Summary: This study demonstrates the impact of MHC-II expression on the interactions between cells in the tumor microenvironment of colorectal cancer, suggesting that low HLA-DR expression may lead to weakened interactions between T cells and APCs, ultimately affecting CTL-mediated anti-tumor activity.
Article
Oncology
William A. A. Hall, J. Joshua Smith
Summary: This article discusses the challenges in the treatment of rectal cancer, including improving initial staging accuracy, choosing the optimal surgical management strategy, ensuring the use of modern radiation therapy approaches, and the importance of organ preservation strategies.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Radiology, Nuclear Medicine & Medical Imaging
Vetri Sudar Jayaprakasam, Janet Alvarez, Dana M. Omer, Marc J. Gollub, J. Joshua Smith, Iva Petkovska
Summary: The diagnosis and treatment of rectal cancer have undergone significant changes, with an increase in incidence in younger populations. This review highlights advances in diagnosis, treatment, and the introduction of nonsurgical management. The article also discusses the use of MRI and endoscopy to assess treatment response and the limitations and future challenges in imaging and endoscopy.
Article
Oncology
Eileen S. Carpenter, Ahmed M. Elhossiny, Padma Kadiyala, Jay Li, Jake McGue, Brian D. Griffith, Yaqing Zhang, Jacob Edwards, Sarah Nelson, Fatima Lima, Katelyn L. Donahue, Wenting Du, Allison C. Bischoff, Danyah Alomari, Hannah R. Watkoske, Michael Mattea, Stephanie The, Carlos E. Espinoza, Meredith Barrett, Christopher J. Sonnenday, Nicholas Olden, Chin-Tung Chen, Nicole Peterson, Valerie Gunchick, Vaibhav Sahai, Arvind Rao, Filip Bednar, Jiaqi Shi, Timothy L. Frankel, Marina Pasca di Magliano
Summary: We characterized the unique microenvironment of the adult human pancreas and discovered the high prevalence of PanIN lesions compared to pancreatic cancer. Fibroblasts and macrophages in pancreatic cancer and peritumoral tissue showed distinct transcriptomic signatures. PanIN epithelial cells in healthy pancreas exhibited remarkable similarity to cancer cells transcriptionally, suggesting early initiation of neoplastic pathways in tumorigenesis.
Article
Biochemical Research Methods
Jin K. Kim, Chao Wu, Michael Del Latto, Yajing Gao, Seo-Hyun Choi, Maria Kierstead, Charles-Etienne Gabriel Sauve, Canan Firat, Almudena Chaves Perez, Jussi Sillanpaa, Chin-Tung Chen, Kayla E. Lawrence, Philip B. Paty, Francisco M. Barriga, John E. Wilkinson, Jinru Shia, Charles L. Sawyers, Scott W. Lowe, Julio Garcia-Aguilar, Paul B. Romesser, J. Joshua Smith
Summary: This article describes a mouse model of rectal cancer that utilizes orthotopic transplantation for rapid tumor organoid engraftment in an immunocompetent setting. The model closely resembles human rectal cancer and provides a accessible approach for preclinical efficacy studies.
CELL REPORTS METHODS
(2022)
Article
Oncology
Bryan C. Szeglin, Chao Wu, Michael R. Marco, Hyun Sung Park, Zeda Zhang, Bing Zhang, Julio Garcia-Aguilar, R. Daniel Beauchamp, X. Steven Chen, J. Joshua Smith
Summary: A gene expression-based profile modulated by SMAD4 was identified, distinguishing high-risk stage II and III colorectal cancer patients and predicting disease-free survival. The profile has prognostic potential for colorectal cancer patients in stage II and III.
Article
Oncology
Abiola Ibraheem, Colin Pillai, Ifeoma Okoye, J. Joshua Smith, Diane Reidy-Lagunes, Grace Macaulay, Olusegun Alatise
Summary: Cancer is a significant healthcare burden in sub-Saharan Africa due to lifestyle changes and longer life expectancy. Globalization of cancer clinical trials in this region could provide opportunities for innovative treatments and showcase the strengths and capabilities for conducting trials in Africa.
JCO GLOBAL ONCOLOGY
(2021)