scholarly journals Immunotherapy for Early Stage Colorectal Cancer: A Glance into the Future

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1990
Author(s):  
Romain Cohen ◽  
Qian Shi ◽  
Thierry André
Keyword(s):  
Colorectal Cancer ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Disease Recurrence ◽  
Prognostic Features ◽  
T Cell Infiltration ◽  
Tumor Mutational Burden ◽  
Patients At Risk ◽  
Selection Of Patients ◽  
Selection Of

Immune checkpoint inhibitors (ICI) have reshaped therapeutic strategies for cancer patients. The development of ICI for early stage colorectal cancer is accompanied by specific challenges: (i) the selection of patients who are likely to benefit from these treatments, i.e., patients with tumors harboring predictive factors of efficacy of ICI, such as microsatellite instability and/or mismatch repair deficiency (MSI/dMMR), or other potential parameters (increased T cell infiltration using Immunoscore® or others, high tumor mutational burden, POLE mutation), (ii) the selection of patients at risk of disease recurrence (poor prognostic features), and (iii) the choice of an accurate clinical trial methodological framework. In this review, we will discuss the ins and outs of clinical research of ICI for early stage MSI/dMMR CC patients in adjuvant and neoadjuvant settings. We will then summarize data that might support the development of ICI in localized colorectal cancer beyond MSI/dMMR.

scholarly journals Exploring the association with disease recurrence of miRNAs predictive of colorectal cancer

2021 ◽  
pp. 172460082110649
Author(s):  
Susanna Zanutto ◽  
Chiara Maura Ciniselli ◽  
Antonino Belfiore ◽  
Valentina Dall’Olio ◽  
Laura Tizzoni ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Stage ◽  
Disease Recurrence ◽  
Rank Test ◽  
P Value ◽  
Alive With Disease ◽  
Patients At Risk ◽  
Signed Rank Test ◽  
Disseminated Disease

Introduction Disease recurrence after surgery is a crucial predictor of poor prognosis in colorectal cancer, where disseminated disease at the time of intervention can also be observed in localized early-stage cases. We evaluated the ability to predict disease recurrence of miRNAs from two signatures that we have found linked to the presence of colorectal cancer (CL signature) or adenoma (HgA signature) in higher-risk subjects. Methods miRNAs from the signatures were studied longitudinally by quantitative real-time polymerase chain reaction in plasma from 24 patients with resectable colorectal cancer collected at the time of surgery and during scheduled follow-up across 36 months. Patients either showed relapse within 36 months (alive with disease (AWD)), or remained disease-free (no evidence of disease (NED)) for the same period. Results Although the signatures did not predict recurrence, expression of the miRNAs from the CL signature decreased 1 year after surgery, and one miRNA of the signature, miR-378a-3p, almost reached significance in the NED subgroup (Wilcoxon signed-rank test: p-value = 0.078). Also, miR-335-5p from the HgA signature was higher in AWD patients before surgery (Kruskal–Wallis test: p-value = 0.019). Conclusions These data, although from a small cohort of patients, support the possible use of miRNAs as non-invasive biomarkers in liquid biopsy-based tests to identify patients at risk of relapse and to monitor them during follow-up.

scholarly journals Emerging Trends for Radio-Immunotherapy in Rectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1374
Author(s):  
Claudia Corrò ◽  
Valérie Dutoit ◽  
Thibaud Koessler
Keyword(s):  
Rectal Cancer ◽  
Tumor Microenvironment ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Tumor Infiltrating Lymphocytes ◽  
T Cell Infiltration ◽  
Emerging Trends ◽  
Tumor Mutational Burden ◽  
Microsatellite Stability

Rectal cancer is a heterogeneous disease at the genetic and molecular levels, both aspects having major repercussions on the tumor immune contexture. Whilst microsatellite status and tumor mutational load have been associated with response to immunotherapy, presence of tumor-infiltrating lymphocytes is one of the most powerful prognostic and predictive biomarkers. Yet, the majority of rectal cancers are characterized by microsatellite stability, low tumor mutational burden and poor T cell infiltration. Consequently, these tumors do not respond to immunotherapy and treatment largely relies on radiotherapy alone or in combination with chemotherapy followed by radical surgery. Importantly, pre-clinical and clinical studies suggest that radiotherapy can induce a complete reprograming of the tumor microenvironment, potentially sensitizing it for immune checkpoint inhibition. Nonetheless, growing evidence suggest that this synergistic effect strongly depends on radiotherapy dosing, fractionation and timing. Despite ongoing work, information about the radiotherapy regimen required to yield optimal clinical outcome when combined to checkpoint blockade remains largely unavailable. In this review, we describe the molecular and immune heterogeneity of rectal cancer and outline its prognostic value. In addition, we discuss the effect of radiotherapy on the tumor microenvironment, focusing on the mechanisms and benefits of its combination with immune checkpoint inhibitors.

scholarly journals Bevacizumab in neoadjuvant treatment of patients with liver metastases from colorectal carcinoma

2010 ◽  
Vol 18 (3) ◽  
pp. 75-78
Author(s):  
Ivan Nikolic ◽  
Svetlana Pavin ◽  
Biljana Kukic ◽  
Bogdan Bogdanovic ◽  
Miroslav Ilic ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Neoadjuvant Treatment ◽  
Hepatic Metastases ◽  
Response Rates ◽  
Control Group ◽  
Significant Difference ◽  
Experimental Group ◽  
Selection Of Patients ◽  
Selection Of

Background: Liver metastases are the leading cause of death in patients with colorectal cancer. Despite advances in chemotherapy, surgical resection of hepatic metastases is still considered the only curative options. However, the majority of patients have inoperable disease at presentation. Perioperative chemotherapy is the most successful way for improved selection of patients for resection. The aim of the study was to demonstrate if and to what extent does bevacizumab, introduced in chemotherapy, increase response rates, and development of liver metastases. Methods: Our study included 50 patients who were divided in two groups. The experimental group included patients who were treated with bevacizumab plus chemotherapy, and the control group included patients who were treated with chemotherapy only. Results: The comparison showed that the patients who were treated with bevacizumab became candidates for resection of liver metastases in higher percentage (85%:52%). In addition, distribution of patients regarding the development of metastases resulted in statistically significant difference. Ratio between the patients with good response from the experimental and the control group was 67%:39%. Ratio of patients with stable disease was 26%:48%, and of patients with progressive disease, it was 7%:3%. The estimate of margin after resection was statistically insignificant. Conclusion: Bevacizumab in combination with chemotherapy in therapy of liver metastases from primary colorectal cancer improves and increases response rates and development of liver metastases.

scholarly journals Management of Localized Muscle-Invasive Bladder Cancer from a Multidisciplinary Perspective: Current Position of the Spanish Oncology Genitourinary (SOGUG) Working Group

2021 ◽  
Vol 28 (6) ◽  
pp. 5084-5100
Author(s):  
Antonio Gómez Caamaño ◽  
Ana M. García Vicente ◽  
Pablo Maroto ◽  
Alfredo Rodríguez Antolín ◽  
Julián Sanz ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Working Group ◽  
Checkpoint Inhibitors ◽  
Imaging Techniques ◽  
Clinical Staging ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive ◽  
Selection Of Patients ◽  
Selection Of

This review presents challenges and recommendations on different aspects related to the management of patients with localized muscle-invasive bladder cancer (MIBC), which were discussed by a group of experts of a Spanish Oncology Genitourinary (SOGUG) Working Group within the framework of the Genitourinary Alliance project (12GU). It is necessary to clearly define which patients are candidates for radical cystectomy and which are candidates for undergoing bladder-sparing procedures. In older patients, it is necessary to include a geriatric assessment and evaluation of comorbidities. The pathological report should include a classification of the histopathological variant of MIBC, particularly the identification of subtypes with prognostic, molecular and therapeutic implications. Improvement of clinical staging, better definition of prognostic groups based on molecular subtypes, and identification of biomarkers potentially associated with maximum benefit from neoadjuvant chemotherapy are areas for further research. A current challenge in the management of MIBC is improving the selection of patients likely to be candidates for immunotherapy with checkpoint inhibitors in the neoadjuvant setting. Optimization of FDG-PET/CT reliability in staging of MIBC and the selection of patients is necessary, as well as the design of prospective studies aimed to compare the value of different imaging techniques in parallel.

scholarly journals Mismatch Repair System Genomic Scars in Gastroesophageal Cancers: Biology and Clinical Testing

2020 ◽  
Vol 2 (4) ◽  
pp. 341-352
Author(s):  
Gianluca Lopez ◽  
Konstantinos Venetis ◽  
Elham Sajjadi ◽  
Nicola Fusco
Keyword(s):  
Mismatch Repair ◽  
State Of The Art ◽  
Checkpoint Inhibitors ◽  
Repair System ◽  
Testing Methods ◽  
Clinical Role ◽  
Stage Disease ◽  
Mismatch Repair System ◽  
Selection Of Patients ◽  
Selection Of

Alterations in the mismatch repair (MMR) system result in genomic instability, neoantigen production, and immune response in cancer. There is evidence that gastroesophageal tumors with MMR deficiency may be susceptible to immune-checkpoint inhibitors treatment, especially in those presenting at advanced-stage disease. Although a number of biomarkers have been developed in histology-agnostic settings to assess MMR status, there is evidence that a tumor-specific testing approach would improve the selection of patients for immunotherapy. However, no testing methods have been developed specifically for gastroesophageal cancers so far. Here, we discuss the state of the art, current advances, and future perspectives of MMR-related biomarkers’ biologic and clinical role in gastroesophageal cancers.

Circulating tumor cells as a possible prognostic tool in newly diagnosed nonmetastatic colorectal cancer?

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 395-395 ◽  
Author(s):  
Loes Scholten ◽  
Leon W. M. M. Terstappen ◽  
Job van der Palen ◽  
Walter Mastboom ◽  
Arjan Tibbe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Disease Free Survival ◽  
Disease Recurrence ◽  
Benign Tumors ◽  
Control Group ◽  
Newly Diagnosed ◽  
Cellsearch System ◽  
Patients At Risk

395 Background: The presence of circulating tumor cells (CTC) is associated with poor prognosis in patients with metastatic colorectal cancer (CRC). The current study was conducted to determine if the presence of CTC prior to surgery in patients with newly diagnosed non-metastatic CRC can identify those patients at risk for disease recurrence. Methods: In a prospective single center study 180 patients with newly diagnosed non-disseminated CRC scheduled for surgery were enrolled and followed up for a median of 41 months. CTC were enumerated with the CellSearch System in 4 aliquots of 7.5 ml of peripheral blood before undergoing surgery. The control group consisted of sixty patients with benign tumors after surgery or colonoscopy. Results: ≥1 CTC/ 30ml of blood were detected in 9 (15%) persons of the control group, and in 41 (23%) CRC patients. From the 180 CRC patients, 44 developed recurrent disease (24%) and 38 patients (21%) died during follow up. Presence of CTC correlated with disease recurrence (p= 0.040) and death (p=0.006). Patients with CTC had a significantly decreased three year Disease Free Survival (DFS) and overall survival (OS) versus those without CTC (DFS 57%vs. 78%, p=0.018 and OS 70% vs. 80%, p=0.003%). Conclusions: Patients with stage I-III CRC with CTC before surgery have a significantly lower 3 years DFS and OS. These findings warrant further development of technology to increased the sensitivity and specificity of CTC detection for incorporation as prognostic marker along side Duke Stage to assess which patients need adjuvant treatment.

scholarly journals PREDICTIVE RESPONSE MARKERS FOR IMMUNE RESPONSE BLOCKS

2020 ◽  
Vol 19 (4) ◽  
pp. 123-131
Author(s):  
G. A. Janus ◽  
A. G. Ievleva ◽  
E. N. Suspitsyn ◽  
V. I. Tyurin ◽  
I. V. Bizin ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Predictive Power ◽  
Checkpoint Inhibitors ◽  
Significant Proportion ◽  
Histocompatibility Complex ◽  
Mutation Burden ◽  
Selection Of Patients ◽  
Selection Of

Despite the unprecedented success in using immune checkpoint inhibitors in the treatment of lung cancer, melanoma, hypermutable tumors of various localization, etc., a significant proportion of patients receiving these drugs do not respond to treatment. Predictive markers routinely used in the selection of patients for immunotherapy, in particular, the level of expression of PD -L1 and the presence of microsatellite instability, have certain limitations. Over the past decade, many other biomarkers designed to predict response to immunotherapy have been proposed, namely: tymor mutation burden, composition of lymphocytic infiltrate; allelic composition of the major histocompatibility complex; relationship between the numbers of different formed elements of blood as well as between its biochemical parameters; microflora of the digestive tract, etc. These markers can directly or indirectly reflect the immunogenicity of the tumor itself, as well as the state of systemic and intratumoral immune response. The predictive power and reliability of these markers are extremely different. When preparing this review, we conducted a literature search for recent studies regarding predictors of efficacy for immune checkpoint inhibitors published in the journals included in the databases, such as Pubmed, Web of Science, and Scopus.

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