A PROSPECTIVE STUDY TO EVALUATE PROGNOSTIC SIGNIFICANCE OF VARIOUS MOLECULAR BIOMARKERS IN TREATMENT OF PATIENTS WITH CENTRAL NERVOUS SYSTEM (CNS) GLIOMAS.

Aim  :

To evaluate the prognostic significance of various molecular biomarkers in treatment of patients with central nervous system gliomas.

Objectives :

Primary objective :

To find association between following molecular biomarkers with treatment outcomes such as  one year overall survival (1 year OS).

-        IDH

-        ATRX

-        P53

-        MGMT

-        1p19q

Secondary objective :

To find association between the above molecular biomarkers with treatment outcomes such as progression free survival (PFS)

INCLUSION CRITERIA:

1. Histopathologically confirmed CNS gliomas (WHO Grade II - IV) (APPENDIX II).
2. Patients age 18 years and older.
3. Karnofsky performance score (KPS) more than equal to 60 (APPENDIX III).
4. Patients who are willing to give informed consent to participate in the study.

EXCLUSION CRITERIA:

1.       Grade I gliomas

2.      Patients aged below 18 years

3.      Karnofsky performance score (KPS)  less than 60

4.      Pregnant and lactating women

5.      Non-glioma tumors of CNS

SAMPLE SIZE :

Cochran formula for Observational Study :

N =  z2x p x (1-p)

e 2

Where,

Proportion of patients who improved clinically = 94 %

Hence P = 0.94

1.96 = z valve for 95% Confidence Level

e = Allowable error = 6 %

Calculated sample size  = 60

Study sample size – Patients who satisfy the inclusion criteria and recruited during the study period**.**

Follow-up :

Patients with low grade gliomas (grade II)  will be followed up 3 – 6 months after completion of RT and then followed by every 3 – 6 months for next one year. Patients with high grade gliomas (grade III, IV) will be followed up 2 – 8 weeks after completion of RT and then followed by every 3 – 6 months for next one year.

Outcome Assessment :

Patients will be assessed with MRI which will be done after 6 months of completion of radiotherapy or when the patient becomes symptomatic which ever is earliest and followed by 2nd MRI after next 6 months. The one year overall survival (OS) is calculated from date of registration or surgery (whichever is earlier) to date of death. The progression free survival (PFS) is calculated from date of registration or surgery (whichever is earlier) to date of progression. Disease progression, response to treatment and any treatment-related toxicity will also be recorded during follow-up visits.

Data collection :

All patient data were entered into a Microsoft Excel spreadsheet and later analyzed using SPSS software version 23 Continuous variables were expressed as means ± standard deviation (SD) or medians, and analyzed using Student’s t-test for normally distributed data or the Wilcoxon rank-sum test for non-parametric data.

Statistical Analysis :

Statistical analysis will be performed by the SPSS program for Windows, version 26.0. Continuous variables will be presented as mean +/- SD, and  categorical variables will be presented as absolute numbers and percentage. Data will be checked for normality before statistical analysis.

Survival analysis will be conducted using Kaplan – Meier method and comparison of survival curves will be performed using log – rank test. Comparison of mean for normally distributed continuous variables will be compared using the unpaired t test, whereas the Mann-Whitney U test will be used for those variables that not be normally distributed. Categorical variables will be analysed using either the chi square test or Fisher’s test.

Statistical Significance

P > 0.05 is not significant

P < 0.05 is significant

P < 0.01 is highly significant