Prognostic haematological biomarkers for predicting terminal illness and end of life in patients with advanced cancers receiving palliative care in a tertiary care centre- a prospective cohort study. a PREDICTIVE BIOCARE study [PREDICTIVE BIOmarker in advanced CAncer patients Receiving End-of-life care.]

All adult patients of either gender with advanced cancer presenting to the Palliative care unit ward and OPD in Dr BRAIRCH, AIIMS, New Delhi and NCI, Jhajjar.

Inclusion criteria:

1. Adult Patients (>18 years of age) with evidence of advanced cancer: Patients with locally advanced or metastatic cancer based on clinical examination and imaging, and not amenable to curative oncological therapy.

2. Patients with a Palliative Prognostic Index of more than 4 (expected survival shorter than 6 weeks).

3. Knows and understands Hindi and English.

4. Able to consent to participation in the study.

Exclusion criteria:

1. Death due to other causes not related to cancer, for example, accidental deaths, deaths in natural calamities.

2. Pre-existing diseases not related to cancer affecting the studied biomarkers, like congenital liver disorders (Dubin-Johnson syndrome, Rotor syndrome), congenital renal disorders, and other congenital diseases like cystic fibrosis, etc.

3. Patients with known haematological disorders, such as sickle cell anaemia and thalassemia, who are already presenting with anaemia.

4. Congenital immunodeficient states like SCID (Severe Combined Immunodeficiency Disorder), CVID (Common Variable Immunodeficiency Disorder), etc.

Study procedure:

After obtaining clearance from the Institute Ethics Committee and CTRI registration, patients presenting to the Department of Onco-Anaesthesia and Palliative Medicine (OPD) or admitted to the ward will be assessed. Patients fulfilling the inclusion criteria, having a Palliative Prognostic Index of more than 4, will be recruited.

Patients will be explained about the study protocol and written informed consent will be taken. Primary caregiver shall also be explained about the study protocol and details of the primary care giver shall be recorded. The patient’s demographic data including the age, gender, primary cancer, radiological imaging details, tumor, node and metastasis (TNM) stage, treatment history and duration of disease will be recorded at their day of recruitment.

Also, blood samples will be drawn on the day of recruitment and the following parameters will be sent for investigation:

As per routine protocol, patients visiting palliative medicine OPD for best supportive care are followed up either weekly or every two weeks, depending on their needs. For this study, after two (2) weeks of baseline assessment, blood samples will be re-sent for further assessment of the trends of the same biomarkers when these patients visit for their follow-up.

At baseline and then on follow-up at 2, 4, and 6 weeks, the patient’s will be assessed using:

Palliative Prognostic Index: 1. Palliative Performance Scale [a) Ambulation b) Activity level and Evidence of disease c) Self-care d) Intake e) Level of consciousness] 2. Oral intake 3. Oedema 4. Dyspnea at rest 5. Delirium (according to DSM-5).

ECOG PS (Eastern Cooperative Oncology Group Performance Score): our inclusion criteria include patients with an ECOG PS of 4. So, in our study in due course of time score will progress to ECOG PS 5.

Scores will be calculated and assigned for 2-, 4-, and 6-week periods.

Patients will continue to receive best supportive care and symptomatic management as deemed necessary.

During the six-week study follow-up period, patient status, including survival and death, will be noted. In the course of follow-up, if they turn terminally sick, telephonic follow-up will be done with their primary caregiver. Additionally, in the event of a missed follow-up, a telephonic confirmation regarding the patient’s status shall be obtained from the primary caregiver.