scholarly journals 823 Spatial analysis of tumor-infiltrating lymphocytes correlates with the response of metastatic colorectal cancer patients treated with vactosertib in combination with pembrolizumab

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A861-A861
Author(s):  
Tae Won Kim ◽  
Keun-Wook Lee ◽  
Joong Bae Ahn ◽  
Young Suk Park ◽  
Gahee Park ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Tumor Infiltrating Lymphocytes ◽  
Operating Characteristics ◽  
Primary Resistance ◽  
Immune Phenotype ◽  
Potential Biomarker ◽  
Biomarker Analysis ◽  
Β Receptor ◽  
Colorectal Cancer Patients

BackgroundPreviously, we presented a promising anti-tumor efficacy (ORR: 16%, mOS: 15.8 months, RECIST) of the combination of vactosertib, a potent and selective TGF-β receptor I, and pembrolizumab (vac+pem) in patients with microsatellite stable metastatic colorectal cancer (MSS mCRC, MP-VAC-204 study). Recent reports showed immune-excluded TIL located in stroma would be closely related to TGF-β signature, which may harbor the primary resistance of pembrolizumab. In this study, we performed an exploratory biomarker analysis of TIL resided in either intra-tumoral or stromal area in pathology slides, and we hypothesized that spatial features of TIL would correlate with the response of vac+pem.MethodsPathology slides stained with H&E were obtained from 31 patients at baseline and 14 patients at cycle 2 in MSS mCRC patients in MP-VAC-204 study. For spatial TIL analysis, we applied an artificial intelligence -powered H&E analyzer, named Lunit SCOPE IO, which automatically detects TIL, tumor and stroma. It calculates the proportion of immune phenotype consists of inflamed, as high TIL density inside tumor area, or immune-excluded, as high TIL density in stroma in whole-slide images. Additionally, PD-L1 and CD8 were stained using multiplex immunohistochemistry to validate immune phenotype assessed by Lunit SCOPE IO.ResultsAt baseline, the proportion of immune-excluded area (immune-excluded score, IES) was positively correlated with the density of CD8-positive cells in stroma area measured by mIHC (coefficient = 0.349), but it was not related to the density of PD-L1-positive cells (coefficient = -0.226). Area under receiver operating characteristics to predict the responder as partial response by RECIST v1.1 by IES and PD-L1 were 0.741 and 0.528. The overall response rate of vac+pem in the patients with high IES > 42.3% was 25% (4 out of 16), while no response was observed in those with low IES (0 out of 15). Overall survival (OS) of vac+pem was significantly prolonged in those with high IES > 42.3% compared to low IES (median OS: not reached versus 6.8 months, P = 0.0097), but it was not different according to PD-L1 level. After treatment of vac+pem, while IES was decreased regardless of treatment response, the proportion of inflamed area was increased in the responders (N=3) but decreased in the non-responders (N=11).ConclusionsImmune-excluded score which reflects TGF-β-driven TIL exclusion into stroma is correlated with anti-tumor response of vac+pem in MSS mCRC. Further investigation on spatial TIL analysis as a potential biomarker should be warranted. (Clinical trial information: NCT03724851)

scholarly journals Negative Hyperselection of Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer Who Received Panitumumab-Based Maintenance Therapy

2019 ◽  
Vol 37 (33) ◽  
pp. 3099-3110 ◽  
Author(s):  
Federica Morano ◽  
Salvatore Corallo ◽  
Sara Lonardi ◽  
Alessandra Raimondi ◽  
Chiara Cremolini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Wild Type ◽  
Primary Resistance ◽  
Molecular Alterations ◽  
Status Interaction ◽  
Colorectal Cancer Patients

PURPOSE We assessed the prognostic/predictive role of primary tumor sidedness and uncommon alterations of anti–epidermal growth factor receptor (EGFR) primary resistance (primary resistance in RAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-EGFR monoclonal antibodies [PRESSING] panel) in patients with RAS/ BRAF wild-type (wt) metastatic colorectal cancer (mCRC) who were randomly assigned to panitumumab plus fluorouracil, leucovorin, and oxaliplatin (FOLFOX-4) induction followed by maintenance with panitumumab with or without fluorouracil (FU) plus leucovorin (LV); Valentino trial (ClinicalTrials.gov identifier: NCT02476045 ). PATIENTS AND METHODS This prespecified retrospective analysis included 199 evaluable patients with RAS/ BRAF wt. The PRESSING panel included the following: immunohistochemistry (IHC) and in situ hybridization for HER2/MET amplification, IHC with or without RNA sequencing for ALK/ROS1/NTRKs/RET fusions, next-generation sequencing for HER2/ PIK3CAex.20/PTEN/ AKT1 and RAS mutations with low mutant allele fraction, and multiplex polymerase chain reaction for microsatellite instability. PRESSING status (any positive biomarker v all negative) and sidedness were correlated with overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in the study population and by treatment arm. RESULTS Overall, left- and right-sided tumors were 85.4% and 14.6%, respectively, and PRESSING-negative and -positive tumors were 75.4% and 24.6%, respectively. At a median follow-up of 26 months, inferior outcomes were consistently observed in right- versus left-sided tumors for ORR (55.2% v 74.1%; P = .037), PFS (8.4 v 11.5 months; P = .026), and OS (2-year rate: 50.2% v 65.1%; P = .062). Similar results were observed in the PRESSING-positive versus PRESSING-negative subgroup for ORR (59.2% v 75.3%; P = .030), PFS (7.7 v 12.1 months; P < .001), and OS (2-year rate: 48.1% v 68.1%; P = .021). The PFS benefit of FU plus LV added to panitumumab maintenance, reported in the study, was independent from sidedness and PRESSING status (interaction for PFS P = .293 and .127, respectively). However, outcomes were extremely poor in patients who received single-agent panitumumab and had right-sided tumors (median PFS, 7.7 months; 2-year OS, 38.5%) or PRESSING-positive tumors (median PFS, 7.4 months; 2-year OS, 47.0%). CONCLUSION The combined assessment of sidedness and molecular alterations of anti-EGFR primary resistance identified a consistent proportion of patients with RAS/ BRAF–wt mCRC who had inferior benefit from initial anti-EGFR–based regimens, particularly after maintenance with single-agent anti-EGFRs.

scholarly journals Influence of Postoperative Changes in Sarcopenia on Long-Term Survival in Non-Metastatic Colorectal Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2410
Author(s):  
Chungyeop Lee ◽  
In-Ja Park ◽  
Kyung-Won Kim ◽  
Yongbin Shin ◽  
Seok-Byung Lim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Medical Center ◽  
The Body ◽  
Term Survival ◽  
Postoperative Changes ◽  
Asan Medical ◽  
Colorectal Cancer Patients

The effect of perioperative sarcopenic changes on prognosis remains unclear. We conducted a retrospective cohort study with 2333 non-metastatic colorectal cancer patients treated between January 2009 and December 2012 at the Asan Medical Center. The body composition at diagnosis was measured via abdominopelvic computed tomography (CT) using Asan-J software. Patients underwent CT scans preoperatively, as well as at 6 months–1 year and 2–3 years postoperatively. The primary outcome was the association between perioperative sarcopenic changes and survival. According to sarcopenic criteria, 1155 (49.5%), 890 (38.2%), and 893 (38.3%) patients had sarcopenia preoperatively, 6 months–1 year, and 2–3 years postoperatively, respectively. The 5-year overall survival (OS) (95.8% vs. 92.1%, hazard ratio (HR) = 2.234, p < 0.001) and 5-year recurrence-free survival (RFS) (93.2% vs. 86.2%, HR = 2.251, p < 0.001) rates were significantly lower in patients with preoperative sarcopenia. Both OS and RFS were lower in patients with persistent sarcopenia 2–3 years postoperatively than in those who recovered (OS: 96.2% vs. 90.2%, p = 0.001; RFS: 91.1% vs. 83.9%, p = 0.002). In multivariate analysis, postoperative sarcopenia was confirmed as an independent factor associated with decreased OS and RFS. Pre- and postoperative sarcopenia and changes in the condition during surveillance were associated with oncological outcomes.

Sign in / Sign up

Export Citation Format

Share Document