ASCO 2021: Review of Neurotumor (Part 1)

1.
The specific genomic risk score can reflect the prognosis of low-grade glioma patients undergoing radiotherapy

1.
The specific genomic risk score can reflect the prognosis of low-grade glioma patients undergoing radiotherapy 1.

The specific genomic risk score can reflect the prognosis of low-grade glioma patients undergoing radiotherapy

The standard treatment of low-grade glioma (LGG) is the maximum safe resection and risk-adaptive adjuvant therapy
.
Although prospective randomized studies have clarified the patients who benefit most from adjuvant chemotherapy, there is still a lack of comparable understanding of adjuvant radiotherapy (RT)

.

We tried to find and verify gene expression patterns related to the different outcomes of LGG patients receiving RT treatment from two large genomics databases
.

David C Qian and others of Emory University used TCGA data to screen out glioma-related genes that are involved in MAP kinase activity, T cell chemotaxis and cell cycle transition: MAP3K15, MAPK10, CCL3, CCL4 and ADAMTS1, and constructed the Genomic Risk Score (GRS)
.

In TCGA, 289 LGG patients received separate adjuvant RT (38 Class II, 30 Class III) or Chemoradiation Therapy (CRT) (51 Class II, 170 Class III) between 2009 and 2015
.
178 LGG patients from CGGA received separate adjuvant RT (40 grade II, 13 grade III) or CRT (41 grade II, 84 grade III) between 2004 and 2016

.

High GRS (defined as GRS in the first third) is significantly associated with a poor prognosis, regardless of age, gender, glioma histology, WHO classification, IDH mutation, 1p/19q co-deletion, and chemotherapy status in the training set Impact (OS HR 2.
74, P<0.
001; PFS HR 1.
61, P = 0.
014)
.
These findings were further verified in the other two data sets

.

In TCGA and CGGA, the relationship between GRS and outcome was only observed in patients who received RT (RT alone or CRT)
.

The significance of this study is to determine the expression characteristics of five genes, stratify the results of LGG patients receiving adjuvant RT, and use an independent genomics database for two rounds of verification
.

The results of LGG patients receiving adjuvant RT were stratified, and two rounds of validation were performed using an independent genomics database
.
The results of LGG patients receiving adjuvant RT were stratified, and two rounds of validation were performed using an independent genomics database

.

2.
Compared with primary lung tumors, the tumor immune microenvironment of brain metastases is immunosuppressed

2.
Compared with primary lung tumors, the tumor immune microenvironment of brain metastases is immunosuppressed 2.
Compared with primary lung tumors, the tumor immune microenvironment of brain metastases is immunosuppressed

Lung cancer is one of the most common causes of brain metastases (BMs) and is always associated with a poor prognosis
.

They performed RNA sequencing (RNA-seq) on 86 formalin-fixed, paraffin-embedded (FFPE) samples of 43 patients’ primary lung tumors and matched brain metastases to comprehensively analyze the tumor immune microenvironment
.

They found that compared with primary lung tumors, brain metastases have reduced tumor infiltrating lymphocytes (TILs) (all 28 immune cell subtypes P<0.
05); activated CD8 T cells and effector memory CD8 T cells in the total number of TILs The proportion of TILs was low (P=0.
028, P<0.
001); the proportion of macrophages and neutrophils in the total amount of TILs was relatively high (P<0.
001, P<0.
01, respectively)

.

Compared with primary lung tumors, some immune-related signatures, including MHC non-class signatures, IFN gamma signatures, and T cell inflammation gene expression profile (GEP) signatures, score significantly lower in brain metastases (P = 0.
004, P = 0.
009, P = 0.
004, respectively), while the scores of MHC-II signatures are higher in brain metastases (P = 0.

045)
.

And found that the distribution of tumor microenvironmental immune types (TMIT) in brain metastases and primary lung tumors is different
.

The distribution of tumor microenvironmental immune type (TMIT) in brain metastases and primary lung tumors is different
.
The distribution of tumor microenvironmental immune type (TMIT) in brain metastases and primary lung tumors is different
.

This study illustrates the immune profile of NSCLC brain metastases, and suggests that compared with primary lung tumors, the tumor immune microenvironment of brain metastases is further immunosuppressed, which may help guide immunotherapy strategies for NSCLC brain metastases
.

Source:
Likun Chen, Lihong Wu, Meichen Li, et al.

J Clin Oncol 39, 2021 (suppl 15; abstr 2020)

3.
Breast cancer brain metastasis, macrophage polarization indicates poor prognosis

3.
Breast cancer brain metastasis, macrophage polarization indicates poor prognosis 3.
Breast cancer brain metastasis, macrophage polarization indicates poor prognosis breast cancer

At present, the complexity of the immune microenvironment in breast cancer (BC) brain metastasis (BM) is still poorly understood
.
Multiple immunofluorescence (mIF) can simultaneously observe several IF-labeled proteins while maintaining spatial information
.
This new technology can be used to comprehensively describe the immune microenvironment of brain metastases, and may provide useful information for guiding new treatment methods
.

Gaia Griguolo and others of the University of Padua in Italy collected clinical data and archived BM samples of 60 BC patients undergoing neurosurgery (2003-2018)
.
Use customized mIF panels to characterize BCBMs, including immune checkpoints and co-inhibitory molecules (CD3, PD1, PD-L1, TIM3, LAG3, CD163) and localization (keratin used to identify tumors) markers
.
Determine the average marker density (positive cells/mm2) through image analysis, and classify the tumor and stroma regions
.
The relationship between the density of immune markers, BC subtype and overall survival (OS) from the diagnosis of BM was also studied
.

diagnosis

They found that at a median follow-up of 43 months, the only clinical variable related to OS was the BC subtype (HR-/HER2- shortest, HER2+ longest, P=0.
02)
.
In the total sample area and the tumor area, no significant difference in marker density was observed according to the BC subtype
.
In the stromal area, significant differences in TIM3+ cell density were observed according to BC subtypes (HR+/HER2- had the highest density, and HER2+ tumors had the lowest density
.

Higher CD163 density (a marker of M2 macrophage polarization) in the tumor and stromal areas is clearly associated with poor OS
.
In the subgroup of HR+/HER2-BCBM patients, the high density of TIM3+ cells in the stromal area was significantly associated with longer OS
.

The conclusion of this study is: in BCBM, the matrix TIM3+ immune infiltration varies according to the BC subtype
.
M2 macrophage polarization is consistently associated with worsening of OS in all BC subtypes, which may represent a potential therapeutic target for these patients
.

In BCBM, the matrix TIM3+ immune infiltration varies according to the BC subtype.
In BCBM, the matrix TIM3+ immune infiltration varies according to the BC subtype.

Source:
Gaia Griguolo et al.

J Clin Oncol 39, 2021 (suppl 15; abstr 2021)

4.
Anti-PD1 and stereotactic radiation, safe and effective for the treatment of brain metastases

4.
Anti-PD1 and stereotactic radiation, safe and effective for the treatment of brain metastases 4.
Anti-PD1 and stereotactic radiation, safe and effective for the treatment of brain metastases

The safety and efficacy of simultaneous use of pembrolizumab (anti-PD1) and stereotactic radiosurgery (SRS) in the treatment of brain metastases (BM) are still unclear
.

Mohammad Khurram Khan and others of Emory University included patients with melanoma or NSCLC to evaluate the anti-PD1+SRS treatment of BM
.

First of all, anti-PD1 treatment has no obvious toxicity
.

Secondly, they also found that the 1-year OS of patients who had previously received treatment and those who had not received the treatment were similar (71.
8% vs.
65.
6%), indicating that SRS has a certain role in overcoming treatment resistance
.

No difference in results was found in the three different SRS groups
.
70% of patients showed early activation of CD8+PD1+Ki67+T cells (within 3 weeks after starting SRS/anti-PD1), showing clinical benefit
.

100% of patients who failed to show early activation of CD8+PD1+Ki67+T cells have progressed
.

Therefore, parallel pembrolizumab (anti-PD-1) and SRS are safe and effective
.
The early activation of CD8+PD1+Ki67+T cells is related to the improvement of curative effect
.

Parallel pembrolizumab (anti-PD-1) and SRS are safe and effective
.
The early activation of CD8+PD1+Ki67+T cells is related to the improvement of curative effect
.
Parallel pembrolizumab (anti-PD-1) and SRS are safe and effective
.
The early activation of CD8+PD1+Ki67+T cells is related to the improvement of curative effect
.

Source:
Mohammad Khurram Khan et al.

J Clin Oncol 39, 2021 (suppl 15; abstr 2022)

 

 

 

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