scholarly journals Adjuvant chemotherapy in stage II and III colon cancer: the role of the “budding and TILs-(tumor-infiltrating lymphocytes) combination” as tumor-host antagonists

2021 ◽  
Author(s):  
Corinna Lang-Schwarz ◽  
Balint Melcher ◽  
Theresa Dregelies ◽  
Zahra Norouzzadeh ◽  
Stefanie Rund-Küffner ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Treatment ◽  
Tumor Infiltrating Lymphocytes ◽  
Treatment Decisions ◽  
Stage Ii ◽  
Stage Iii ◽  
Tumor Budding ◽  
Stage Iii Colon Cancer ◽  
Infiltrating Lymphocytes

Abstract Purpose To analyze the influence of adjuvant chemotherapy on the combination of tumor budding and tumor-infiltrating lymphocytes (TILs) in stage II and III colon cancer and to elucidate its potential value for adjuvant treatment decisions. Methods 306 patients with stage II and 205 patients with stage III colon cancer diagnosed between 2005 and 2016 who had undergone surgery in a curative setting were enrolled. Budding and TILs were assessed according to the criteria of the International Tumor Budding Consensus Conference (ITBCC) and the criteria of the International TILs Working Group (ITWG). Combinations of budding and TILs were analyzed, and the influence of adjuvant chemotherapy was assessed. Results In stage II colon cancer, stratification into the four budding/TILs groups showed no significant differences in overall survival (OS) between the chemotherapy and the surgery-alone group, not even in cases with high-risk features. In stage III colon cancer, patients with low budding/high TILs benefited significantly from chemotherapy (p=0.005). Patients with high budding/low TILs as well as high budding/high TILs showed a trend to benefit from adjuvant treatment. However, no chemotherapy benefit was seen for the low budding/low TIL group. Conclusions The budding/TIL combination identified subgroups in stage II and III colon cancer with and without benefit from adjuvant treatment. The results this study suggest that the combination of budding and TILs as tumor-host antagonists might be an additional helpful tool in adjuvant treatment decisions in stage II and III colon cancer.

Fluorouracil Plus Leucovorin as Effective Adjuvant Chemotherapy in Curatively Resected Stage III Colon Cancer: Results of the Trial adjCCA-01

2001 ◽  
Vol 19 (6) ◽  
pp. 1787-1794 ◽  
Author(s):  
Rainer Porschen ◽  
Andreas Bermann ◽  
Thomas Löffler ◽  
Gregor Haack ◽  
Klaus Rettig ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Treatment ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Postoperative Treatment ◽  
Free Survival ◽  
Stage Iii Colon Cancer ◽  
Resected Stage ◽  
Disease Free

PURPOSE: Adjuvant postoperative treatment with fluorouracil (5-FU) and levamisole in curatively resected stage III colon cancer significantly reduces the risk of cancer recurrence and improves survival. Biochemical modulation of 5-FU with leucovorin has resulted in increased remission rates in metastatic colorectal cancer, thus reflecting an increased tumor-cell kill. The impact of 5-FU plus leucovorin on survival and tumor recurrence was analyzed in comparison with the effects of 5-FU plus levamisole in the prospective multicentric trial adjCCA-01. PATIENTS AND METHODS: Patients with a curatively resected International Union Against Cancer stage III colon cancer were stratified according to T, N, and G category and randomly assigned to receive one of the two adjuvant treatment schemes: 5-FU 400 mg/m2 body-surface area intravenously in the first chemotherapy course, then 450 mg/m2 × 5 days; 12 cycles, plus leucovorin 100 mg/m2 (arm A), or 5-FU plus levamisole (Moertel scheme; arm B). RESULTS: Six hundred eighty (96.9%) of 702 patients enrolled onto this study were eligible. After a median follow-up time of 46.5 months, the 5-FU plus leucovorin combination significantly improved disease-free survival (P = .037) and significantly decreased overall mortality (P = .0089) in comparison with 5-FU plus levamisole. In a multivariate proportional hazards model, adjuvant chemotherapy emerged as a significant prognostic factor for survival (P = .0059) and disease-free survival (P = .03). Adjuvant treatment with 5-FU plus levamisole as well as with 5-FU plus leucovorin was generally well tolerated; only a minority of patients experienced grade 3 and 4 toxicities. CONCLUSION: After a curative resection of a stage III colon cancer, adjuvant treatment with 5-FU plus leucovorin is generally well tolerated and significantly more effective than 5-FU plus levamisole in reducing tumor relapse and improving survival.

Adjuvant therapy for stage II and III colon cancer in elderly patients: NCDB analysis.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 863-863
Author(s):  
Samip R. Master ◽  
Lawrence Shi ◽  
Chintan Shah ◽  
Runhua Shi
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Single Agent ◽  
Stage Ii ◽  
Stage Iii ◽  
Stage Iii Colon Cancer ◽  
Survival Difference ◽  
Multi Agent ◽  
Comorbidity Index

863 Background: Data on safety and efficacy of adjuvant chemotherapy for stage II and III colon cancer in elderly patients is area of controversy as these patients are underrepresented in clinical trials. We did a retrospective analysis of Medicare patients aged 70 or older with stage II and stage III colon cancer to investigate the adjuvant chemotherapy effect on colon cancer patients’ survival. Methods: Data was analyzed from 110, 993 men and women (≥ 70 years of age) registered in the National Cancer Database (NCDB) who were diagnosed with AJCC Stage II and Stage III colon cancer between 2004 and 2012 and had follow-ups to end of 2013. The primary predictor variable was adjuvant chemotherapy received, and overall survival was the outcome variable. Only patients with Medicare insurance were investigate for ease of analysis. Additional variables addressed and adjusted included gender, age, race, Charlson Comorbidity Index, the level of education, income, grade of tumor, distance traveled, facility type and diagnosing/treating facility. Results: The mean age was 79.5 years and SD was 5.9 years. In multivariate analysis, after adjusting for secondary predictor variables, receipt of adjuvant chemotherapy was a statistically significant predictor of overall survival of the stage II and stage III colon cancer. Relative to patients who did not receive adjuvant chemotherapy, the patients who got single agent adjuvant chemotherapy had 47.7% and those who were treated with multi agent chemotherapy had 49.8% decreased risk of mortality. There was no significant survival difference between single agent and multi agent adjuvant chemotherapy. Among the factors analyzed, age, gender, race, comorbidity index, diagnosing /treating facility and grade of tumor were found to be significant predictors of survival. Conclusions: Among the patients aged 70 years or older with stage II and stage III colon cancer, adjuvant chemotherapy lead to improved survival outcomes. However, survival difference between single agent vs multi agent adjuvant chemotherapy was not statistically significant.

scholarly journals Adjuvant systemic chemotherapy for stages II and III colon cancer after complete resection: a clinical practice guideline

2016 ◽  
Vol 23 (6) ◽  
pp. 418 ◽  
Author(s):  
B.M. Meyers ◽  
R. Cosby ◽  
F. Quereshy ◽  
D. Jonker
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Practice Guideline ◽  
Stage Ii ◽  
Stage Iii ◽  
Cochrane Library ◽  
Stage Iii Colon Cancer ◽  
Resected Stage ◽  
Stage Ii Colon Cancer

Background Updated practice guidelines on adjuvant chemotherapy for completely resected colon cancer are lacking. In 2008, Cancer Care Ontario’s Program in Evidence-Based Care developed a guideline on adjuvant therapy for stages ii and iii colon cancer. With newer regimens being assessed in this patient population and older agents being either abandoned because of non-effectiveness or replaced by agents that are more efficacious, a full update of the original guideline was undertaken.Methods Literature searches (January 1987 to August 2015) of medline, embase, and the Cochrane Library were conducted; in addition, abstracts from the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress were reviewed (the latter for January 2007 to August 2015). A practice guideline was drafted that was then scrutinized by internal and external reviewers whose comments were incorporated into the final guideline.Results Twenty-six unique reports of eighteen randomized controlled trials and thirteen unique reports of twelve meta-analyses or pooled analyses were included in the evidence base. The 5 recommendations developed included 3 for stage ii colon cancer and 2 for stage iii colon cancer.Conclusions Patients with completely resected stage iii colon cancer should be offered adjuvant 5-fluorouracil (5fu)–based chemotherapy with or without oxaliplatin (based on definitive data for improvements in survival and disease-free survival). Patients with resected stage ii colon cancer without “high-risk” features should not receive adjuvant chemotherapy. For patients with “high-risk” features, 5fu-based chemotherapy with or without oxaliplatin should be offered, although no clinical trials have been conducted to conclusively demonstrate the same benefits seen in stage iii colon cancer.

scholarly journals Programmed death ligand 1 (PD-L1) in colon cancer and its interaction with budding and tumor-infiltrating lymphocytes (TILs) as tumor-host antagonists

2021 ◽  
Author(s):  
Corinna Lang-Schwarz ◽  
Balint Melcher ◽  
Arndt Hartmann ◽  
Simone Bertz ◽  
Theresa Dregelies ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Immune Therapy ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Treatment Decisions ◽  
Tumor Budding ◽  
Prognostic Impact ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Infiltrating Lymphocytes

Abstract Purpose To analyze the role of programmed death ligand 1 (PD-L1) immunohistochemisty in the context of tumor microenvironment in colon cancer (CC) with focus on the interaction between tumor budding and tumor-infiltrating lymphocytes (TILs) and to elucidate its potential value for immunooncologic treatment decisions. Methods Three hundred forty seven patients with CC, stages I to IV, were enrolled. PD-L1 immunohistochemistry was performed using two different antibodies (clone 22C3 pharmDx, Agilent and clone QR1, Quartett). Tumor proportion score (TPS) as well as immune cell score (IC) was assessed. Budding and TILs were assessed according to the criteria of the International Tumor Budding Consensus Conference (ITBCC) and International TILs Working Group (ITWG). Correlation analyses as well as survival analyses were performed. Results PD-L1 positivity significantly correlated with TILs > 5% and MMR deficiency, and PD-L1-positive cases (overall and IC) showed significantly longer overall survival (OS) with both antibodies.The parameters “high grade,” “right-sidedness,” and “TILS > 5% regardless of MMR status” evolved as potential parameters for additional immunological treatment decisions. Additionally, TPS positivity correlated with low budding. More PD-L1-positive cases were seen in both high TIL groups. The low budding/high TIL group showed longer disease-free survival and longer OS in PD-L1-positive cases. Conclusion Overall, PD-L1 positivity correlated with markers of good prognosis. PD-L1 immunohistochemistry was able to identify parameters as additional potential candidates for immune therapy. Furthermore, it was able to stratify patients within the low budding/high TIL group with significant prognostic impact.

Microsatellite instability status as a predictive marker of clinical outcome from FOLFOX adjuvant chemotherapy in stage III colon cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 493-493 ◽  
Author(s):  
A. Zaanan ◽  
J. Flejou ◽  
J. Emile ◽  
P. Validire ◽  
C. Louvet ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Clinical Outcome ◽  
Microsatellite Instability ◽  
Adjuvant Treatment ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Rank Test ◽  
Free Survival ◽  
Stage Iii Colon Cancer

493 Background: The addition of oxaliplatin to 5-fluorouracil (5-FU; FOLFOX regimen) was demonstrated to improve the adjuvant treatment of stage III colon cancer. For patients with microsatellite instability (MSI) tumors, several studies suggested a lack of benefit from 5-FU adjuvant chemotherapy but very little data are available regarding FOLFOX adjuvant therapy. The aim of this study was to further assess the value of MSI status as a marker of clinical outcome from FOLFOX adjuvant chemotherapy in stage III colon cancer. Methods: This multicentric retrospective study included 223 unselected patients with stage III colon cancer treated by FOLFOX adjuvant chemotherapy between 2003 and 2007. MSI status was determined by immunohistochemistry as the absence of MLH1, MSH2 or MSH6 expression. Disease-free survival (DFS) and relapse-free survival (RFS) were analyzed according to the MSI status using Kaplan Meier method and compared by log-rank test. Results: Twenty three tumors (10.3%) were MSI. The rate of 3-year DFS was 88.6% and 76.6% for MSI and MSS groups, respectively (HR=0.64; 95% CI, 0.25 to 1.60; P=0.34). The rate of 3-year RFS was 88.6% and 76.7% for MSI and MSS groups, respectively (HR=0.52; 95% CI, 0.20 to 1.30; P=0.18). Conclusions: A trend toward longer survival was observed for patients with MSI tumors compared with those with MSS tumors but the differences in survival were not significant. Interestingly, DFS at 3-years of patients with stage III MSI tumors treated by FOLFOX was higher in our series (88.6%) than in the largest study published for patients treated by 5-FU-based adjuvant chemotherapy (around 67.5%) or surgery alone (around 62.5%) (Sargent et al, JCO 2010). These observations suggest that adding oxaliplatin to 5-FU re-establishes a benefit of adjuvant treatment in the stage III MSI population. These results should be confirmed by analyzing materials of previously completed trials comparing FOLFOX to 5-FU such as the MOSAIC study. [Table: see text]

Duration of FOLFOX adjuvant chemotherapy in high-risk stage II and stage III colon cancer with deficient DNA mismatch repair.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4075-4075
Author(s):  
Zehua Wu ◽  
Huabin Hu ◽  
Chao Wang ◽  
Yan Huang ◽  
Yanhong Deng
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Therapy Group ◽  
Stage Ii ◽  
Stage Iii ◽  
Dna Mismatch ◽  
Stage Iii Colon Cancer

4075 Background: In the IDEA collaboration, noninferiority was not confirmed for 3 months versus 6 months of FOLFOX adjuvant chemotherapy among patients with high-risk stage II and stage III colon cancer (CC). Patients with deficient DNA mismatch repair (dMMR) have a good prognosis, but for whom, whether limiting the duration of adjuvant therapy will compromise oncologic outcomes remains undefined. We evaluated the impact of 3 months of FOLFOX adjuvant chemotherapy or surgery alone in comparison with 6 months of FOLFOX on disease-free survival (DFS) in dMMR CC patients. Methods: This retrospective study included all consecutive patients who underwent curative surgical resection for high-risk stage II or III dMMR CC between May, 2011 and July, 2019. Prognostic factors were analyzed using Cox models, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Results: A total of 242 dMMR CC patients were included (43.4% high-risk stage II, 56.6% stage III). The patients received 6 months of FOLFOX adjuvant chemotherapy (n = 66; median cycles [rang] = 12 [10-12]), 3 months of FOLFOX (n = 87; median cycles [rang] = 6 [4-8]), or surgery alone (n = 89). Three groups were generally well balanced, although more patients with stage III were in the 6-month therapy group (74.2%), compared with the 3-month therapy group (57.5%) and the surgery alone group (42.7%). As compared with 6 months of FOLFOX adjuvant chemotherapy in the overall population, 3 months therapy reduced DFS in multivariable analysis (HR, 2.78; 95CI, 1.18 to 6.47; P = 0.02), similar to surgery alone (HR, 2.30; 95CI, 0.99 to 5.38; P = 0.05). In the subgroup analysis, a therapy duration of 6 months was statistically superior to a duration of 3 months only in the patients with stage III, with a 3-year rate of DFS of 86.2% versus 70.8% (HR, 3.06; 95% CI, 1.14 to 8.19; P = 0.026). Conclusions: This study supports the 6-month duration of FOLFOX adjuvant chemotherapy in stage III dMMR CC.

scholarly journals Adjuvant Chemotherapy for Stage III Colon Cancer

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2679 ◽  
Author(s):  
Julien Taieb ◽  
Claire Gallois
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Treatment ◽  
Standard Of Care ◽  
Disease Recurrence ◽  
Stage Iii ◽  
Clinical Practices ◽  
Duration Of Treatment ◽  
Risk Of Recurrence ◽  
Stage Iii Colon Cancer

In patients with stage III colon cancer (CC), adjuvant chemotherapy with the combination of oxapliplatin to a fluoropyrimidine (FOLFOX or CAPOX) is a standard of care. The duration of treatment can be reduced from 6 months to 3 months, depending on the regimen, for patients at low risk of recurrence, without loss of effectiveness and allowing a significant reduction in the risk of cumulative sensitive neuropathy. However, our capacity to identify patients that do really need this doublet adjuvant treatment remains limited. In fact, only 30% at the most will actually benefit from this adjuvant treatment, 50% of them being already cured by the surgery and 20% of them experiencing disease recurrence despite the adjuvant treatment. Thus, it is necessary to be able to better predict individually for each patient the risk of recurrence and the need for adjuvant chemotherapy together with the need of new treatment approaches for specific subgroups. Many biomarkers have been described with their own prognostic weight, without leading to any change in clinical practices for now. In this review, we will first discuss the recommendations for adjuvant chemotherapy, and then the different biomarkers described and the future perspectives for the management of stage III CC.

scholarly journals Transcriptional Subtyping and CD8 Immunohistochemistry Identifies Patients With Stage II and III Colorectal Cancer With Poor Prognosis Who Benefit From Adjuvant Chemotherapy

2018 ◽  
pp. 1-15 ◽  
Author(s):  
Wendy L. Allen ◽  
Philip D. Dunne ◽  
Simon McDade ◽  
Enya Scanlon ◽  
Maurice Loughrey ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Tumor Infiltrating Lymphocytes ◽  
Standard Of Care ◽  
Classification Systems ◽  
Stage Ii ◽  
Stage Iii ◽  
Clinical Value ◽  
Transcriptomic Profiling ◽  
Infiltrating Lymphocytes

Purpose Transcriptomic profiling of colorectal cancer (CRC) has led to the identification of four consensus molecular subtypes (CMS1 to 4) that have prognostic value in stage II and III disease. More recently, the Colorectal Cancer Intrinsic Subtypes (CRIS) classification system has helped to define the biology specific to the epithelial component of colorectal tumors; however, the clinical value of these classification systems in the prediction of response to standard-of-care adjuvant chemotherapy remains unknown. Patients and Methods Using samples from four European sites, we assembled a novel cohort of patients with stage II and III CRC (n = 156 samples) and performed transcriptomic profiling and targeted sequencing and generated a tissue microarray to enable integrated multiomics analyses. We also accessed data from two published cohorts of patients with stage II and III CRC: GSE39582 and GSE14333 (n = 479 and n = 185 samples, respectively). Results The epithelial-rich CMS2 subtype of CRC benefitted significantly from treatment with adjuvant chemotherapy in both stage II and III disease ( P = .02 and P < .001, respectively), whereas the CMS3 subtype significantly benefitted in stage III only ( P = .001). After CRIS substratification of CMS2, we observed that only the CRIS-C subtype significantly benefitted from treatment with adjuvant chemotherapy in stage II and III disease ( P = .0081 and P < .001, respectively), whereas the CRIS-D subtype significantly benefitted in stage III only ( P = .0034). We also observed that CRIS-C patients with low levels of CD8+ tumor-infiltrating lymphocytes were most at risk for relapse in both stage II and III disease (log-rank P = .0031; hazard ratio, 12.18 [95% CI, 1.51 to 98.58]). Conclusion Patient stratification using a combination of transcriptional subtyping and CD8 immunohistochemistry analyses is capable of identifying patients with poor prognostic stage II and III disease who benefit from adjuvant standard-of-care chemotherapy. These findings are particularly relevant for patients with stage II disease, where the overall benefit of adjuvant chemotherapy is marginal.

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