scholarly journals Prognostic and Predictive Cross-Roads of Microsatellite Instability and Immune Response to Colon Cancer

2020 ◽  
Vol 21 (24) ◽  
pp. 9680
Author(s):  
Luigi Laghi ◽  
Francesca Negri ◽  
Federica Gaiani ◽  
Tommaso Cavalleri ◽  
Fabio Grizzi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Microsatellite Instability ◽  
Adjuvant Treatment ◽  
Early Stage ◽  
Tumor Infiltrating Lymphocytes ◽  
Staging System ◽  
Risk Groups ◽  
Tnm Staging ◽  
Molecular Features ◽  
Colon Cancers

Understanding molecular features of colon cancer has shed light on its pathogenesis and progression. Over time, some of these features acquired clinical dignity and were incorporated in decision making. Namely, microsatellite instability (MSI) due to mismatch repair of defects, which primarily was adopted for the diagnosis of Lynch syndrome, became recognized as the biomarker of a different disease type, showing a less aggressive behavior. MSI tumors harbor high amounts of tumor infiltrating lymphocytes (TILs) due to their peculiar load in neoantigens. However, microsatellite stable colon cancer may also show high amounts of TILs, and this feature is as well associated with better outcomes. High TIL loads are in general associated with a favorable prognosis, especially in stage II colon cancer, and therein identifies a patient subset with the lowest probability of relapse. With respect to post-surgical adjuvant treatment, particularly in stage III, TILs predictive ability seems to weaken along with the progression of the disease, being less evident in high risk patients. Moving from cohort studies to the analysis of a series from clinical trials contributed to increase the robustness of TILs as a biomarker. The employment of high TIL densities as an indicator of good prognosis in early-stage colon cancers is strongly advisable, while in late-stage colon cancers the employment as an indicator of good responsiveness to post-surgical therapy requires refinement. It remains to be clarified whether TILs could help in identifying those patients with node-positive cancers to whom adjuvant treatment could be spared, at least in low-risk groups as defined by the TNM staging system.

scholarly journals Improving Risk Stratification of Early Oral Tongue Cancer with TNM-Immune (TNM-I) Staging System

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3235
Author(s):  
Alhadi Almangush ◽  
Ibrahim O. Bello ◽  
Ilkka Heikkinen ◽  
Jaana Hagström ◽  
Caj Haglund ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tongue Cancer ◽  
Early Stage ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Staging System ◽  
Oral Tongue ◽  
Oral Tongue Cancer ◽  
Important Player ◽  
Infiltrating Lymphocytes

Although patients with early-stage oral tongue squamous cell carcinoma (OTSCC) show better survival than those with advanced disease, there is still a number of early-stage cases who will suffer from recurrence, cancer-related mortality and worse overall survival. Incorporation of an immune descriptive factor in the staging system can aid in improving risk assessment of early OTSCC. A total of 290 cases of early-stage OTSCC re-classified according to the American Joint Committee on Cancer (AJCC 8) staging were included in this study. Scores of tumor-infiltrating lymphocytes (TILs) were divided as low or high and incorporated in TNM AJCC 8 to form our proposed TNM-Immune system. Using AJCC 8, there were no significant differences in survival between T1 and T2 tumors (p > 0.05). Our proposed TNM-Immune staging system allowed for significant discrimination in risk between tumors of T1N0M0-Immune vs. T2N0M0-Immune. The latter associated with a worse overall survival with hazard ratio (HR) of 2.87 (95% CI 1.92–4.28; p < 0.001); HR of 2.41 (95% CI 1.26–4.60; p = 0.008) for disease-specific survival; and HR of 1.97 (95% CI 1.13–3.43; p = 0.017) for disease-free survival. The TNM-Immune staging system showed a powerful ability to identify cases with worse survival. The immune response is an important player which can be assessed by evaluating TILs, and it can be implemented in the staging criteria of early OTSCC. TNM-Immune staging forms a step towards a more personalized classification of early OTSCC.

Microsatellite Instability as a Predictor of Outcomes in Colorectal Cancer in the Era of Immune-Checkpoint Inhibitors

2021 ◽  
Vol 22 ◽  
Author(s):  
Csongor György Lengyel
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Immune Checkpoint ◽  
Predictive Value ◽  
Checkpoint Inhibitors ◽  
Tumor Infiltrating Lymphocytes ◽  
Primary Objective ◽  
Dna Mismatch ◽  
Dominant Component ◽  
Colon Cancers

: The microsatellite instable phenotype resulting from errors in DNA mismatch repair proteins accounts for as far as 15 to 20% of non-hereditary colon cancers but is scarce in rectal cancer. It has been shown that the increased existence of tumor-specific neoantigens in hypermutated tumors is correlated with higher tumor-infiltrating lymphocytes (TILs) and overexpression of immune checkpoint receptors and ligands, mainly PD-1 and PD-L1. In particular, the data gained up to now gives evidence that neoantigen recognition constitutes a dominant component in the course of immunotherapies. This review's primary objective is to describe current approvals and summarize present knowledge about the outcomes of immuno-oncology treatment of microsatellite instable colorectal cancer (CRC). The secondary objective is to give a narrative report about testing methodologies, prognostics, and the predictive value of microsatellite instability. For this purpose, a literature review was performed, focusing on published clinical trial results, ongoing clinical trials and timelines, testing methods, and prognostic and predictive value of MSI. Following four recent FDA approvals of immunotherapy of MSI-high CRC, further work should be warranted by pathology societies towards standardization and rising concordance and reproducibility across the IHC/MSI testing landscape in order to facilitate professionals to offer better survival options for patients with CRC.

Eight-Signature Classifier for Prediction of Nasopharyngeal Carcinoma Survival

2011 ◽  
Vol 29 (34) ◽  
pp. 4516-4525 ◽  
Author(s):  
Hai-Yun Wang ◽  
Bing-Yu Sun ◽  
Zhi-Hua Zhu ◽  
Ellen T. Chang ◽  
Ka-Fai To ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Validation Cohort ◽  
Staging System ◽  
Risk Groups ◽  
Tnm Staging ◽  
Expression Level ◽  
Support Vector ◽  
Svm Classifier ◽  
Patient Counseling ◽  
Histologic Subtype

Purpose Currently, nasopharyngeal carcinoma (NPC) prognosis evaluation is based primarily on the TNM staging system. This study aims to identify prognostic markers for NPC. Patients and Methods We detected expression of 18 biomarkers by immunohistochemistry in NPC tumors from 209 patients and evaluated the association between gene expression level and disease-specific survival (DSS). We used support vector machine (SVM) –based methods to develop a prognostic classifier for NPC (NPC-SVM classifier). Further validation of the NPC-SVM classifier was performed in an independent cohort of 1,059 patients. Results The NPC-SVM classifier integrated patient sex and the protein expression level of seven genes, including Epstein-Barr virus latency membrane protein 1, CD147, caveolin-1, phospho-P70S6 kinase, matrix metalloproteinase 11, survivin, and secreted protein acidic and rich in cysteine. The NPC-SVM classifier distinguished patients with NPC into low- and high-risk groups with significant differences in 5-year DSS in the evaluated patients (87% v 37.7%; P < .001) in the validation cohort. In multivariate analysis adjusted for age, TNM stage, and histologic subtype, the NPC-SVM classifier was an independent predictor of 5-year DSS in the evaluated patients (hazard ratio, 4.9; 95% CI, 3.0 to 7.9) in the validation cohort. Conclusion As a powerful predictor of 5-year DSS among patients with NPC, the newly developed NPC-SVM classifier based on tumor-associated biomarkers will facilitate patient counseling and individualize management of patients with NPC.

QIM19-124: Does Virtual Navigation Improve Care Continuity and Compliance in Patients With Early Stage Colon Cancer?

2019 ◽  
Vol 17 (3.5) ◽  
pp. QIM19-124
Author(s):  
Dayna Crawford ◽  
Brook Blackmore ◽  
Jeremy Ortega ◽  
Erica Williams
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Stage I ◽  
Stage Iii ◽  
Nccn Guidelines ◽  
Care Continuity ◽  
Colon Cancers ◽  
Follow Up Care

Background: Colon cancer is the 3rd most common cancer in men and women combined, with an occurrence rate of 4.49% for men and 4.15% for women. The 2018 expectation is 50,630 deaths related to colon cancer in the United States (American Cancer Society Facts and Figures 2018). Early detection is increasing with nearly 45% of colon cancers diagnosed as stage I/II (Sarah Cannon Cancer Registry 2015). Treatment for early stage I/II colon cancer patients usually involves surgery then surveillance. On-site navigators perform their duties by patient need and barriers to care. Late stage III/IV colon cancer patients require more assistance and face more barriers, which often leaves early stage I/II patients without an advocate. This disparity can lead to lower rates of follow-up care for early stage I/II patients. Sarah Cannon created a program for virtual colon navigation (VCN) to determine if early stage I/II patients benefit from a virtual navigator who offers support by phone throughout their disease process. Objectives: The goal was to increase early stage I/II patients’ knowledge of their cancer and convey the importance of compliance with follow-up care, such as repeat colonoscopy as recommended by their physician and NCCN Guidelines. Methods: By developing software that utilizes artificial intelligence, Sarah Cannon created an automated process to identify colon cancer patients at the time of diagnosis. This technology then routes positive pathology reports to a VCN who contacts the early stage I/II patients by telephone, ensuring patient connection to the suitable physician for treatment. The VCN helps patients understand their diagnosis, provides education, assesses barriers to care, connects to resources, provides emotional support, and offers assistance with follow-up for physician visits, imaging and procedures such as colonoscopies, based upon NCCN Guidelines and physician guidelines. The VCN also connects stage III/IV patients with an on-site navigator in their region for more hands-on navigation. Results: Through September 2018, Sarah Cannon navigated 734 colon cancers, 332 stage I/II and 402 stage III/IV. With our increased capacity, Sarah Cannon/HCA maintained a 98% rate of follow-up care with new diagnoses of all stages of colon cancer. Conclusions: The VCN program allowed Sarah Cannon/HCA to improve care continuity and compliance based upon NCCN Guidelines for early stage I/II colon cancer patients throughout 5 regions and 37 facilities.

Long-term follow-up of women enrolled in a randomized trial of adjuvant chemotherapy for early stage ovarian cancer (ICON1)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5509-5509 ◽  
Author(s):  
A. C. Swart
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Treatment ◽  
Early Stage ◽  
Risk Groups ◽  
P Value ◽  
Long Term Follow Up

5509 Background: ICON1 and a meta-analysis of all relevant trials demonstrated an improvement in 5 year recurrence-free and overall survival (RFS and OS) for women with early-stage epithelial ovarian cancer (ES EOC) treated with adjuvant chemotherapy compared to no adjuvant chemotherapy. We aimed to determine if this initial benefit is maintained long-term and whether benefit is different with different risk groups of patients defined by stage, grade and histology. Method: 477 women with ES EOC were recruited from centres in Italy (271 women) UK (195) Switzerland (11) between August 1991 and January 2000. 5-year results were presented at ASCO 2001. Systematic long-term follow up was planned and completed in May 2006. Results: With a median follow-up of 9.2 years, 168 women have developed recurrent disease or died and 144 women have died. The Hazard Ratio (HR) for RFS of 0.70 in favour of adjuvant chemotherapy (95% CI 0.52–0.95 p= 0.023) translated into an improvement of 10-year absolute RFS of 10% from 57 to 67%. For OS, HR was 0.74 (95% CI 0.53–1.02 p= 0.066), a corresponding improvement in 10-year absolute OS of 8% from 64% to 72%. 26% of patients died from causes other than ovarian cancer. Stage I patients were grouped as low (Ia, grade 1), medium (Ia grade 2, Ib or Ic grade 1) and high risk (Ia, grade 3, Ib or IC grade 2 or 3, any clear cell). The test of interaction between risk groups and adjuvant treatment for RFS and OS was 0.055 and 0.13, respectively. The HR, 95%CI and p value are summarised in the table . Conclusions The long-term benefit of adjuvant treatment on RFS is confirmed. There is clear evidence that adjuvant chemotherapy reduces the risk of recurrence/death or death alone in high-risk patients but not in the low-risk group. [Table: see text] [Table: see text]

Improving the prediction of colon cancer survival after curative resection.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 552-552
Author(s):  
Aliyah Pabani ◽  
Winson Y. Cheung ◽  
Matthew Mazurek ◽  
Jennifer L. Spratlin ◽  
Karen E. Mulder ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Lymph Nodes ◽  
Classification System ◽  
Early Stage ◽  
Tnm Classification ◽  
Tnm Staging ◽  
Primary Adenocarcinoma ◽  
Curative Intent ◽  
N2 Disease ◽  
Staging Systems

552 Background: Cancer staging systems convey valuable prognostic information to both clinicians and patients. Currently, colon cancer is staged according to the American Joint Committee on Cancer (AJCC) TNM classification system. However, survival estimates for patients with the same stage of colon cancer may vary considerably due to other factors including age, sex, grade, and number of lymph nodes sampled. The objectives of this study are to 1) assess the accuracy of the seventh edition of the TNM classification system in predicting survival of patients with primary colon cancer after curative-intent surgery, and 2) evaluate the utility of incorporating additional demographic and tumor variables beyond TNM staging in improving prognostic accuracy. Methods: Patients with curative-intent resection of a first primary adenocarcinoma of the colon at the time of referral to the Cross Cancer Institute between 2004 and 2007 were identified from the Alberta Cancer Registry. We constructed three multivariate Cox’s proportional hazard models to explore the effect of supplementing TNM staging with additional demographic and tumor variables in predicting overall survival (OS). Results: 559 consecutive patients with complete chart records were identified. 52 % (n=290) were male; median age was 74. In the first model based only on T and N elements, N2 disease was correlated with increased mortality (hazard ratio [HR], 2.546; p<0.0001). When the number of lymph nodes examined (HR, 0.980; p=0.034) and number of metastatic lymph nodes detected (HR, 1.094; p<0.0001) were substituted for the N-staging element, both variables correlated positively and negatively with outcome, respectively. Finally, when tumor grade, sex and age were incorporated into the model, number of examined lymph nodes (HR, 0.980; p=0.029) and those containing tumor (HR, 1.093; p<0.0001) remained independent predictors of OS. Conclusions: Incorporating readily available demographic and tumor variables, such as age, sex and number of lymph nodes examined, can enhance the current TNM staging system and improve prognostication in early stage colon cancer.

scholarly journals Construction and Validation of a Novel Immunosignature for Overall Survival in Uveal Melanoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Chufeng Gu ◽  
Xin Gu ◽  
Yujie Wang ◽  
Zhixian Yao ◽  
Chuandi Zhou
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Immune Cell ◽  
Risk Group ◽  
Staging System ◽  
Risk Groups ◽  
Tnm Staging ◽  
High Risk Group ◽  
Immune Cell Infiltration ◽  
Tnm Staging System

ObjectivesUveal melanoma (UM) is the most common primary intraocular malignancy in adults, and immune infiltration plays a crucial role in the prognosis of UM. This study aimed to generate an immunological marker-based predictive signature for the overall survival (OS) of UM patients.MethodsSingle-sample gene-set enrichment analysis (ssGSEA) was used to profile immune cell infiltration in 79 patients with UM from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate least absolute shrinkage and selection operator (LASSO) Cox regressions were used to determine the prognostic factors for UM and construct the predictive immunosignature. Receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and calibration curves were performed to evaluate the clinical ability and accuracy of the model. In addition, the predictive accuracy was compared between the immunosignature and the Tumor, Node, Metastasis (TNM) staging system of American Joint Committee on Cancer (AJCC). We further analyzed the differences in clinical characteristics, immune infiltrates, immune checkpoints, and therapy sensitivity between high- and low-risk groups characterized by the prognostic model.ResultsHigher levels of immune cell infiltration in UM were related to a lower survival rate. Matrix metallopeptidase 12 (MMP12), TCDD inducible poly (ADP-ribose) polymerase (TIPARP), and leucine rich repeat neuronal 3 (LRRN3) were identified as prognostic signatures, and an immunological marker-based prognostic signature was constructed with good clinical ability and accuracy. The immunosignature was developed with a concordance index (C-index) of 0.881, which is significantly better than that of the TNM staging system (p &lt; 0.001). We further identified 1,762 genes with upregulated expression and 798 genes with downregulated expression in the high-risk group, and the differences between the high- and low-risk groups were mainly in immune-related processes. In addition, the expression of most of the immune checkpoint-relevant and immune activity-relevant genes was significantly higher in the high-risk group, which was more sensitive to therapy.ConclusionWe developed a novel immunosignature constructed by MMP12, TIPARP, and LRRN3 that could effectively predict the OS of UM.

Review of completed and ongoing trials of capecitabine-based adjuvant therapy in patients with early-stage colon cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 495-495
Author(s):  
J. Cassidy ◽  
N. Scotto ◽  
E. Diaz-Rubio
Keyword(s):  
Colon Cancer ◽  
Adjuvant Treatment ◽  
Early Stage ◽  
Single Agent ◽  
Phase Iii ◽  
Stage Iii ◽  
Treatment Regimens ◽  
Phase Iii Trials ◽  
Early Stage Colon Cancer ◽  
Resected Stage

495 Background: Capecitabine is an established alternative to 5-FU in gastrointestinal cancers. In metastatic colorectal cancer, capecitabine is non-inferior to 5-FU and capecitabine + oxaliplatin (XELOX) is non-inferior to FOLFOX4. Capecitabine is also an effective adjuvant treatment for early-stage colon cancer. Here we review the evidence available from completed studies of adjuvant capecitabine and describe ongoing trials in this setting. Methods: The X-ACT trial included 1,987 patients (pts) with resected stage III disease receiving either capecitabine (n=1,004) or bolus 5-FU/LV (n=983). NO16968 included 1,886 pts with resected stage III disease receiving either XELOX (n=944) or 5-FU/LV (n=942). The primary efficacy endpoint of both trials was DFS. Other large phase III trials of capecitabine in high-risk stage II/stage III pts include AVANT (XELOX + bevacizumab vs. FOLFOX4 ± bevacizumab), QUASAR2 (capecitabine vs. capecitabine + bevacizumab), SCOT (capecitabine or 5-FU/LV + oxaliplatin 12w vs. 24w), and a Japanese study of single-agent capecitabine. Results: In X- ACT, capecitabine was at least equivalent to 5-FU/LV in terms of DFS (HR=0.88; 95% CI, 0.77–1.01) and OS (HR=0.86; 95% CI, 0.74–1.01). In a preplanned multivariate analysis, capecitabine led to significantly superior DFS (p=0.02) and OS (p=0.02) vs. bolus 5-FU/LV [Twelves et al. WCGIC 2010]. In NO16968, DFS was significantly superior for XELOX vs. 5-FU/LV (HR=0.80; 95% CI, 0.69–0.93; p=0.0045) [Haller et al. ECCO-ESMO 2009]. There was a trend towards improvement in OS with XELOX (HR=0.87; 95% CI, 0.72–1.05; p=0.1486); follow-up is ongoing. Capecitabine-based therapy had an acceptable safety profile in both trials [Twelves et al. NEJM 2005; Schmoll et al. JCO 2007]. Data have yet to be reported from the AVANT, QUASAR2, SCOT and Japanese trials, although results from these trials in over 15,000 pts are awaited with interest. Conclusions: Adjuvant capecitabine is non-inferior to 5-FU/LV when given as monotherapy and superior to 5-FU/LV when given in combination with oxaliplatin. Capecitabine should be considered as a standard component of adjuvant treatment regimens for pts with stage III disease. [Table: see text]

Completion of adjuvant chemotherapy with Cape/CAPOX in colon cancer: A retrospective database study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15116-e15116
Author(s):  
Edward Chu ◽  
Xue Wang ◽  
Maxfield Frohlich ◽  
Melody Tran ◽  
Won Chan Lee
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Treatment ◽  
Healthcare Costs ◽  
Early Stage ◽  
Unmet Need ◽  
Oral Chemotherapy ◽  
Completion Rates ◽  
Eligibility Criteria ◽  
Early Stage Colon Cancer

e15116 Background: Fluorouracil-based adjuvant chemotherapy has been shown to improve survival of patients with early-stage colon cancer. Suboptimal adherence to oral chemotherapy, such as capecitabine, remains a serious issue and reduces treatment efficacy. Patient barriers to adherence include adverse effects and high medical costs. This study assesses the completion rates and associated factors in patients on capecitabine monotherapy (Cape) and capecitabine with oxaliplatin (CAPOX) for adjuvant treatment of early-stage colon cancer. Methods: Patients with a primary/secondary diagnosis of early-stage colon cancer between April 2013-March 2017, and 1+ claim of Cape or CAPOX within 60 days of colectomy were identified from the MarketScan Commercial/Medicare Database. Therapy completion rates (treatment ≥7 cycles) were calculated. Multivariate logistic regressions analyses were used to assess the factors (patients’ age, gender, payer type, geography, comorbidities, healthcare costs, etc.) associated with treatment completion. Results: A total of 679 patients met the eligibility criteria (mean age ± SD: 57.3 ± 11.5 years, 54% male), of which 382 (56%) were on Cape (mean age ± SD: 60.2±12.4) and 297 (44%) on CAPOX (mean age ± SD: 53.6±9.0). Completion rates were 43% in Cape and 42% in CAPOX. The baseline overall mean monthly healthcare cost was significantly higher in non-completers vs. completers (Cape: $9,870 vs $7,169, P=0.003; CAPOX: $10,009 vs $8,068, P=0.01). Multivariate logistic regression showed that patients <65 years of age on CAPOX were more likely to complete treatment than patients ≥65 years on CAPOX (Odds Ratio=5.1, P=0.03). Conclusions: Cape and CAPOX completion rates are suboptimal in patients with early-stage colon cancer. Non-completion of therapy is associated with significantly higher baseline healthcare costs for both Cape and CAPOX, as is older age for CAPOX. The low completion rates highlight the unmet need for more effective strategies to optimize oral chemotherapy for the adjuvant treatment of early-stage colon cancer. [Table: see text]

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