Author : Dr.

Shweta Wadhwa
Co-authors : Dr. Abhijeet Ghaytidhak, Dr. Mridul Malhotra, Dr. Kumar Prabhash, Dr. Vanita
Noronha, Dr. Amit Joshi, Dr. Vijay Patil, Dr. Abhishek Mahajan.
Tata Memorial centre, Mumbai, India.
doc.shweta16@gmail.com
 75 patients who had EGFR molecular Associations between EGFR mutation
profiling results (38 EGFR + ve and 37 status and clinical features, specifically
EGFR - ve) with positive brain findings age, sex, smoking, TNM stage, and
and had pre and post treatment imaging variables, as well as brain
imaging were evaluated. metastasis, were analysed using logistic
regression analysis

Out of 162 cases included in the study, 71 were EGFR positive and 91 were EGFR negative. Out of 71 EGFR positive cases, 38 were had brain metastasis and remaining , 33
showed no e/o brain metastasis. Out of 91 EGFR negative cases, 37 had brain metastasis and remaining 54 showed no e/o metastasis.
RESULTS P value P value
Univariate analysis Multivariate analysis
T2 borders 0.00 0.00
Number 0.00 0.01
Time from diagnosis to development of metastasis 0.00 0.04
Diffusion restriction 0.001 0.04
Meningeal involvement 0.04 0.04
Response to therapy 0.001 0.001
Oedema 0.01 0.08
Sex 0.5
Smoking 0.9
Stage at the time of presentation 0.1
Extra cranial metastasis 0.2
Site 0.08
Size of largest lesion 0.3
Mass effect 0.4
 ALK mutation constitutes 4-5% of NSCLC and have a high risk of developing brain
metastases (20%) at the time of the initial diagnosis, dramatically influencing patient’s
quality of life and their prognosis.

 NCCN and ESMO guidelines recommend early screening with MRI Brain in patients with
stage II-IV NSCLC.

 Literature on feature analysis of NSCLC brain metastases on MRI as biomarkers for

predicting ALK mutation is limited and less investigated.

 Recognition of MR imaging characteristics favouring a pattern can help initiate treatment

in advanced cases, which are amenable to rapid progression while waiting for molecular
confirmation.
 The aim of our study was to evaluate the semantic MRI-R parameters of NSCLC
brain metastases and their correlation with ALK mutation status.
We analysed data of 969 patients with
molecular profiling test results available
between Dec 2011 to Nov 2018.

467 patients tested positive for ALK and 502 were ALK
negative. 81 patients in ALK + and 103 patients in ALK
negative group had brain metastases on initial staging
evaluation on MRI Brain.

According to our inclusion-exclusion criteria, we included

75 patients (46 ALK + and 29 ALK -) with pre and post Rx
imaging available and who did not undergo prior local
therapy (WBRT). Patients on systemic chemotherapy were
included.
 Material and methods
Clinical Parameters Radiological parameters
Age Number of lesions
Sex Multiparametric MRI was performed
Location in all
and size
cases.
SmokingAssociations
history T2w morphology,
between mutation status andborders
clinicalstatus
Performance features specificallyConsistency
age, sex, smoking,
histology, TNM stage and imaging variables of
CNS symptoms
brain metastasis, were analyzedNecrosis
using descriptive
analysis (chi square test) and univariate logistic
Hemorrhage
regression analysis.
Edema
Mass effect
Diffusion restriction
Enhancement
Meningeal involvement
 Out of 75 cases, 46 were ALK positive and 29 were ALK negative.

 50 were males and 25 females.

 Out of 75 NSCLC cases studied, 62 (83%) cases were adenocarcinomas and

remaining 13 (17%) were squamous cell carcinoma.

 Out of 46 ALK positives, 45 (98%) were adenocarcinoma histology and one was
squamous cell Ca.

 Out of 46 ALK positive cases - 28 (71%) were <50 years age.

 Out of 46 ALK positive cases - 40 (87%) were non smokers.

 IMAGING PARAMETERS (MRI-R)
Total = 75, 46 ALK positive and 29 ALK negative cases were subjected to MRI-R analysis.
LESION MORPHOLOGY CONSISTENCY ALK POSITIVE (TOTAL=46) ALK NEGATIVE (TOTAL=29)
Solid 33 (71.7%) 17 (58.6%)
 ALK positive cases were more solid than cystic, while
ALK negative had equal incidence of solid and cystic Cystic 13 (28.3%) 12 (41.4%)
consistency. T2W PERIPHERAL SOLID
33 (71.7%) 3 (10.3 %)
RIM
 Hypointense peripheral solid rim in ALK positive ENHANCEMENT
with fuzzy/infiltrative borders.
Ring 39 (84.8%) 10 (34.5%)
 Well defined borders and no solid rim in ALK Patchy 7 (15.2%) 19 (65.5%)
negative.
T2W BORDERS
 ALK positive showed thick ring enhancement while Fuzzy 34(73.9 %) 6 (20.7%)
patchy enhancement in ALK negative.
Defined 12 (26.1%) 23(79.3 %)

 Peripheral restriction of the solid rim was consistent DIFFUSION RESTRICTION

with ALK positive status.
Peripheral 35(76 %) 3 (11%)
Lesions in ALK negative group showed focal central Central/focal 11 (24%) 26(89 %)
restriction on DW images.
MENINGEAL INVOLVEMENT
 Meningeal involvement seen in ALK positive group. Present 25(54.3 %) 5 (17.2%)
Absent 21 (45.7%) 24(82.8 %)
 Results (significant) p value on univariate logistic regression
analysis

Histology 0.000
Smoking history 0.000
T2w morphology 0.000
T2w borders 0.000
Diffusion restriction 0.001
Enhancement 0.000
Meningeal involvement 0.002
Number of lesions 0.002

Results (Statistically insignificant) p value on univariate analysis

Size of the lesion 0.282
Site of the lesion 0.344
Perilesional edema 0.404
Hemorrhage within lesion 0.396
Consistency 0.178
Necrosis 0.369
T2W– fuzzy/infiltrative borders of POST CONTRAST- Thick ring DWI – peripheral restriction
ADC
peripheral solid rim enhancement of solid rim

MRI brain show metastatic lesions in ALK positive

adenocarcinoma lung
 MRI brain show metastatic lesions in ALK negative adenocarcinoma lung

1) T2W- solid lesion with defined Post Contrast- Uniform

DWI- complete restriction ADC- complete restriction
borders enhancement

2)T2W- cystic with well defined Post Contrast- peripheral thin rim
DWI- Focal central restriction ADC-Focal central restriction
borders enhancement
• Radiogenomics is a rapidly evolving field of research aimed at identifying
imaging biomarkers useful for non-invasive genotyping.

• It can capture tumor heterogeneity, can be performed repeatedly for treatment

monitoring, and can be performed in malignancies for which biopsy is not
available.