Immunological nomograms predicting prognosis and guiding adjuvant chemotherapy in stage II colorectal cancer.

499 Background: The type, abundance, and location of tumor-infiltrating lymphocytes (TILs) have been associated with prognosis in colorectal cancer. The objective of this study was to assess the prognostic role of TILs and develop a nomogram for accurate prognostication of stage II colorectal cancer. Methods: Immunohistochemistry was conducted to assess the densities of intraepithelial and stromal CD3+, CD8+, CD45RO+ and FOXP3+ TILs, and to estimate PD-L1 expression in tumor cells for 168 patients with stage II colorectal cancer. The prognostic roles of these features were evaluated using COX regression model, and nomograms were established to stratify patients into low and high-risk groups and compare the benefit from adjuvant chemotherapy. Results: In univariate analysis, patients with high intraepithelial or stromal CD3+, CD8+, CD45RO+ and FOXP3+ TILs were associated significantly with better relapse-free survival (RFS) and overall survival (OS), except for stromal CD45RO+ TILs, whereas PD-L1 expression wasn't associated with RFS or OS. In multivariate analysis, patients with high intraepithelial CD3+ and stromal FOXP3+ TILs were associated with better RFS (p < 0.001 and p = 0.032, respectively), while only stromal FOXP3+ TILs was an independent prognostic factor for OS (p = 0.031). The nomograms were well calibrated and showed a c-index of 0.751 and 0.757 for RFS and OS, respectively. After stratifying into low and high-risk groups, the high-risk group exhibited a better OS from adjuvant chemotherapy (3-year OS of 81.9% v 34.3%, p = 0.006). Conclusions: These results may help improve the prognostication of stage II colorectal cancer and identify a high-risk subset of patients who appeared to benefit from adjuvant chemotherapy.

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GCC expression in lymph nodes (LNs) as a significant determinant of recurrence in stage II colon cancer (CC) patients (pts).

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.369 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 369-369 ◽

Cited By ~ 1

Author(s):

D. J. Sargent ◽

Q. Shi ◽

B. M. Bot ◽

M. B. Resnick ◽

M. O. Meyers ◽

...

Keyword(s):

High Risk ◽

Adjuvant Chemotherapy ◽

Cox Regression ◽

Risk Group ◽

Recurrence Risk ◽

High Risk Group ◽

Stage Ii ◽

Significant Determinant ◽

Recurrence Rates ◽

The Relationship

369 Background: A multi-center prospectively specified retrospective study Validating Indicators to Associate Recurrence (VITAR) is assessing the relationship between guanylyl cyclase C (GCC) gene expression in formalin fixed LNs and recurrence risk in stage II CC pts not treated with adjuvant chemotherapy. Here we report the preplanned initial analysis performed with 241 pts. Methods: GCC mRNA was quantified by RT-qPCR using FFPE LNs tissues from untreated stage II CC pts diagnosed from 1999-2006 with at least 10 LN examined blinded to clinical outcomes. Cox regression models examined the relationship between GCC nodal status and the prespecified primary endpoint of recurrence risk. Results: Twenty-ninepts (12%) had a disease recurrence or cancer death, median follow-up was 60 months and median LNs examined was 15. The ratio of the number of GCC+ LNs over the total number of informative LNs (LNR) significantly predicted higher recurrence risk for 84 pts classified as high risk (HR, 2.38; p=0.02). The estimated 5-yr recurrence rates were 10% and 27% for the low and high risk group, respectively. After adjusting for age, T stage, number of LNs assessed, and MMR status, the significant association remained (HR, 2.61; 95% CI, 1.17-5.83; p=0.02). In a subset of 181 pts with negative margin, T3 tumor only and ≥12 LN examined, the GCC LNR had a HR for recurrence of 5.06 (95% CI 1.61-15.91, p=0.003), translating into 5-yr recurrence rates of 4% among low risk pts and 27% for the high-risk group. Conclusions: Our results suggest that GCC expression in LNs is a significant determinant of recurrence in appropriately staged CC pts not treated with adjuvant chemotherapy. The validation component of the study is ongoing. [Table: see text] [Table: see text]

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JCOG1805 (PanDRa-BD study): A randomized controlled study of adjuvant chemotherapy for stage II colorectal cancer patients at high-risk of developing recurrence according to T-stage and three selected pathological factors (Pn, DR, and BD).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.tps3621 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. TPS3621-TPS3621

Author(s):

Megumi Ishiguro ◽

Hideki Ueno ◽

Atsuo Takashima ◽

Junki Mizusawa ◽

Keita Sasaki ◽

...

Keyword(s):

Colorectal Cancer ◽

Risk Factors ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Multicenter Study ◽

Prognostic Value ◽

Stage Ii ◽

Randomized Controlled ◽

T Stage ◽

Stage Ii Colorectal Cancer

TPS3621 Background: Adjuvant chemotherapy for stage II colorectal cancer (CRC) still remains controversial. Although the NCCN and ESMO guidelines recommend adjuvant chemotherapy for patients with “high-risk features,” the survival benefit has not been confirmed. We reviewed the evidence levels for prognostic values of risk factors, because lack of their robustness is a major source of uncertainty regarding the optimal indication of adjuvant chemotherapy. Consequently, on top of the T-stage, three pathological factors—perineural invasion (Pn), tumor budding (BD), and desmoplastic reaction (DR)—were selected as robust risk factors of recurrence. Among the conventional factors, the prognostic value of Pn had been well validated in a multicenter study conducted by the Japanese Society for Cancer of the Colon and Rectum (JSCCR; Am J Surg Path 2013), but others were deemed suboptimal in terms of the prognostic value. BD and DR are novel tumor- and stroma-factors, respectively, associated with cancer microenvironment at the tumor front. According to the JSCCR and ITBCC 2016 criteria, tumors are graded as BD1, BD2, or BD3. The DR heterogeneity is categorized into Mature, Intermediate, and Immature patterns based on site-specific products of cancer-associated fibroblasts—keloid-like collagen and myxoid stroma. According to a recent prospective multicenter study, BD and DR characterization represent a higher level of prognostic value than other conventional factors (SACURA trial; J Clin Oncol 2019, Br J Cancer 2021). Based on the four selected risk factors, we can exclude the patient group with favorable prognosis (i.e., > 90% of 5-year RFS), which accounts for approximately 40% of the total population, resulting in enabling us to identify the concentrated population of high risk of developing recurrence. Methods: The Japan Clinical Oncology Group (JCOG) launched a randomized controlled phase III trial to evaluate the superiority of adjuvant chemotherapy in terms of relapse-free survival (RFS) over observation only in stage II CRC patients aged 20–80 years having one or more of the following risk factors: pathological T4, Pn, BD3, and non-Mature DR. Patients are randomised, in a 1:1:1 ratio, to [A] observation, [B] capecitabine monotherapy for 6 months, or [C] capecitabine and oxaliplatin (CAPOX) for 3 months. A total of 1680 patients will be accrued from 54 Japanese institutions assuming 3-year RFS with [A] to be 82% and expected 5% increase in 3-year RFS for [B] and [C] with one-sided alpha of 2.5% and power of 80% for each pair comparison. Patient enrollment was started in January 2020 and 170 patients have been enrolled until January 2021. This trial has been registered at Japan Registry of Clinical Trials as jRCTs031190186. Clinical trial information: jRCTs031190186.

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