The maturation stage of tumoral tertiary lymphoid structures to predict recurrence risk in localized colorectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15083-e15083
Author(s):  
Florian Posch ◽  
Karina Silina ◽  
Ulf Petrausch ◽  
Sebastian Leibl ◽  
Axel Muendlein ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Structural Equation ◽  
Critical Role ◽  
Multivariable Analysis ◽  
Recurrence Risk ◽  
Maturation Stage ◽  
Maturation Stages ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures

e15083 Background: The tumor immune infiltrate and organized lymphocytic aggregates within the tumor microenvironment, known as tertiary lymphoid structures (TLS), play a critical role in cancer. We hypothesize that the maturation stage of TLS harbors prognostic information on recurrence risk in patients (pts) with non-metastatic colorectal cancer (nmCRC). Methods: In a comprehensive immunofluorescence and clinical analysis of 111 pts with UICC stage II & III nmCRC (median age: 65 yrs; female: n = 53 (48%); stage III: n = 69 (62%)), we quantified the number and maturation status of tumor-associated TLS in baseline surgical specimens:[1] Early TLS (E-TLS, composed of dense lymphocytic aggregates without follicular dendritic cells (FDCs), [2] Primary follicle-like TLS (PFL-TLS, having FDCs but no germinal center (GC) reaction), and [3] Secondary follicle-like TLS (SFL-TLS, having an active GC reaction). The 3-year incidence of recurrence was the primary endpoint of this study, which occurred in 19 pts (3-year recurrence risk = 18.3%). Results: Most TLS formed in tissue adjacent to the tumor. The median number of TLS/mm of tumor perimeter was 1.0 [25th-75th percentile: 0.5-1.7]. The average proportions of different TLS maturation stages were 56% of E-TLS [40-78], 20% of PFL-TLS [6-37], and 16% of SFL-TLS [0-32]. A structural equation model was fitted to summarize the TLS counts and maturation stages into a TLS maturation immunoscore for predicting recurrence. 3-year recurrence risks were 31.7% (95%CI: 17.2-47.3), 15.9% (5.7-30.5), and 9.4% (2.4-22.4) in pts in the 1st, 2nd, and 3rd tertile of the score (Gray’s test p = 0.05). A higher score was significantly associated with a lower recurrence risk (Hazard ratio (HR) for 10 units increase = 0.76, 95%CI: 0.59-0.97, p = 0.03), and this association prevailed in multivariable analysis adjusting for age, ECOG performance status, stage, and adjuvant chemotherapy (Adjusted HR = 0.73, 0.54-0.99, p = 0.05). Conclusions: Tumors of nmCRC pts with a very low risk of recurrence are characterized by an increased fraction of mature TLS comprising FDCs and GCs. If confirmed prospectively, adjuvant chemotherapy may be avoided in nmCRC pts with a high TLS maturation score.

scholarly journals Infiltrating pattern and prognostic value of tertiary lymphoid structures in resected non-functional pancreatic neuroendocrine tumors

2020 ◽  
Vol 8 (2) ◽  
pp. e001188
Author(s):  
Wu-Hu Zhang ◽  
Wen-Quan Wang ◽  
Xuan Han ◽  
He-Li Gao ◽  
Shuai-Shuai Xu ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Prognostic Value ◽  
Who Classification ◽  
Critical Role ◽  
External Validation ◽  
Tnm Stage ◽  
Pancreatic Neuroendocrine Tumors ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures ◽  
Validation Set

BackgroundTertiary lymphoid structures (TLS) are associated with favorable survival and play a critical role in most solid tumors. However, investigations of TLS are lacking in patients with grade 1 or grade 2 (G1/G2) non-functional pancreatic neuroendocrine tumors (NF-PanNETs). This study aimed to investigate the presence, cellular composition, association with tumor-infiltrating immune cells, and prognostic value of TLS in G1/G2 NF-PanNETs.MethodsTumor tissues from a 182-patient Fudan cohort and a 125-patient external validation set were assessed by H&E staining, immunohistochemistry, and/or multispectral fluorescent immunohistochemistry.ResultsTLS were identified in more than one-third of patients with G1/G2 NF-PanNETs and were located peritumorally, either just outside the tumor tissue or in the stromal area. TLS were mainly composed of B-cell follicles with germinal centers and T-cell zones with dendritic cells. Kaplan-Meier analyses showed that the presence of TLS correlated with both longer recurrence-free survival (RFS, p<0.001) and overall survival (OS, p=0.001), but the number of TLS had no prognostic significance. Multivariate Cox-regression analyses demonstrated that the presence of TLS, WHO classification, and 8th edition American Joint Committee on Cancer (AJCC8th) tumor-node-metastasis (TNM) stage were independent prognostic factors for RFS (p=0.004, p=0.001, and p<0.001, respectively) and OS (p=0.009, p=0.008, and p=0.019, respectively). These results were confirmed using an external validation set. Finally, a nomogram incorporating the presence of TLS was constructed to predict the probability of 5-year RFS of resected G1/G2 NF-PanNETs, which improved on the current WHO classification and AJCC8th TNM stage.ConclusionsThe presence of TLS is an independent and favorable predictor of resected G1/G2 NF-PanNETs, which may play a role in cancer immunobiology.

scholarly journals Efficacy of Adjuvant Chemotherapy According to the Classification of Recurrence Risk Based on Systemic Inflammatory Markers in Patients With Liver Metastases of Colorectal Cancer

2019 ◽  
Vol 39 (9) ◽  
pp. 5039-5045
Author(s):  
MASATSUNE SHIBUTANI ◽  
HISASHI NAGAHARA ◽  
TATSUNARI FUKUOKA ◽  
YASUHITO ISEKI ◽  
KOSEI HIRAKAWA ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Liver Metastases ◽  
Inflammatory Markers ◽  
Recurrence Risk

PS3-05 The chemokine network in the formation of tertiary lymphoid structures in colorectal cancer

Cytokine ◽  
2010 ◽  
Vol 52 (1-2) ◽  
pp. 83
Author(s):  
F. Marchesi ◽  
A.P. Martin ◽  
G.C. Furtado ◽  
P. Allavena ◽  
S.A. Lira ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures

scholarly journals Association of IL-36γ with tertiary lymphoid structures and inflammatory immune infiltrates in human colorectal cancer

2018 ◽  
Vol 68 (1) ◽  
pp. 109-120 ◽  
Author(s):  
Aliyah M. Weinstein ◽  
Nicolas A. Giraldo ◽  
Florent Petitprez ◽  
Catherine Julie ◽  
Laetitia Lacroix ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Human Colorectal Cancer ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures

scholarly journals ctDNA to Guide Adjuvant Therapy in Localized Colorectal Cancer (CRC)

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2869
Author(s):  
Laura Masfarré ◽  
Joana Vidal ◽  
Concepción Fernández-Rodríguez ◽  
Clara Montagut
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Adjuvant Chemotherapy ◽  
Residual Disease ◽  
Early Stage ◽  
Recurrence Risk ◽  
Circulating Tumor Dna ◽  
Key Points ◽  
The Impact ◽  
Critical Overview

Currently, the standard treatment for patients with localized colorectal cancer (CRC) includes surgical resection followed by adjuvant chemotherapy based on clinicopathological features. Recurrence risk stratification in those patients is of utmost importance to guide clinicians to avoid both under- and overtreatment. Recently, the concept of minimal residual disease (MRD) has emerged as the detection of circulating tumor DNA (ctDNA) carrying tumor-specific genomic or epigenomic alterations in the bloodstream of patients after surgery. Emerging studies described how the detection of MRD is a powerful prognostic biomarker to identify patients at higher risk of recurrence and who will potentially benefit the most from a systemic adjuvant treatment. Based on that unprecedented finding, several clinical trials involving stage II and III CRC patients are ongoing evaluating the impact of ctDNA guided treatment by escalating or deescalating adjuvant chemotherapy based on ctDNA MRD detection. This review provides a critical overview of current perspectives of liquid biopsy in early-stage CRC including technical, biological, and clinical key points, as well as ongoing ctDNA-based clinical trials that ultimately aim to improve clinical outcomes of patients with CRC.

scholarly journals Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer

2020 ◽  
Vol 6 (4) ◽  
pp. 283-296 ◽  
Author(s):  
Antonia K Roseweir ◽  
James H Park ◽  
Sanne ten Hoorn ◽  
Arfon GMT Powell ◽  
Susan Aherne ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Recurrence Risk ◽  
Stage Iii

scholarly journals Recurrence Risk after Radical Colorectal Cancer Surgery—Less Than before, But How High Is It?

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3308 ◽  
Author(s):  
Erik Osterman ◽  
Klara Hammarström ◽  
Israa Imam ◽  
Emerik Osterlund ◽  
Tobias Sjöblom ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Adjuvant Treatment ◽  
Recurrence Risk ◽  
Accurate Estimate ◽  
Tumour Cells ◽  
Recurrence Rates ◽  
Colorectal Cancer Surgery

Adjuvant chemotherapy aims at eradicating tumour cells sometimes present after radical surgery for a colorectal cancer (CRC) and thereby diminish the recurrence rate and prolong time to recurrence (TTR). Remaining tumour cells will lead to recurrent disease that is usually fatal. Adjuvant therapy is administered based upon the estimated recurrence risk, which in turn defines the need for this treatment. This systematic overview aims at describing whether the need has decreased since trials showing that adjuvant chemotherapy provides benefits in colon cancer were performed decades ago. Thanks to other improvements than the administration of adjuvant chemotherapy, such as better staging, improved surgery, the use of radiotherapy and more careful pathology, recurrence risks have decreased. Methodological difficulties including intertrial comparisons decades apart and the present selective use of adjuvant therapy prevent an accurate estimate of the magnitude of the decreased need. Furthermore, most trials do not report recurrence rates or TTR, only disease-free and overall survival (DFS/OS). Fewer colon cancer patients, particularly in stage II but also in stage III, today display a sufficient need for adjuvant treatment considering the burden of treatment, especially when oxaliplatin is added. In rectal cancer, neo-adjuvant treatment will be increasingly used, diminishing the need for adjuvant treatment.

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