Bowel cancer is common. Patients with bowel cancer often have a low blood count called anaemia. Anaemia is caused by the cancer bleeding. Anaemia is often worse after surgery. It can make patients feel tired, weak and out of breath. Anaemia can also make recovery more difficult. Anaemia may cause other things like infections and mean a higher risk of cancer coming back. The immune system is less effective in anaemia. The immune system fights infections and detects/battles cancer.
We want to compare outcomes for anaemic patients who have had surgery to cure their cancer. We want to know if patients with anaemia have more problems after their operations. We also want to know if they wait longer for chemotherapy or are less likely to get it. Finally, we want to know if cancer returns more often, or more quickly in anaemic patents.
This study is important. If anaemic patients have worse outcomes following surgery, we could make treating anaemia more of a priority following surgery.
Colorectal cancer (CRC) is the third most common cancer. Iron deficiency anaemia (IDA) is present at diagnosis in approximately 60% of patients. IDA in the perioperative period is associated with poorer outcomes, including increased cancer recurrence. We will investigate associations of post-operative anaemia on patient outcomes.
We will undertake a retrospective open cohort study of individuals >18 years with CRC and an elective, potentially curative resection as coded by ICD10 codes in HES from 1st Jan 2000 to 31st Dec 2022.
We will extract data on the patient’s haemoglobin at presentation and following surgery (within 6 weeks) from CPRD Aurum dataset. Patients who are anaemic post-operatively will give us the exposed cohort, those who are not anaemic will give us the comparator group. We are adjusting for anaemia at presentation as data suggests this may be a surrogate marker for more advanced disease.
In our groups of CPRD Aurum patients linked to HES admitted patient care data we will examine the association between anaemia in the post-operative period with outcomes. Our research questions are:
When compared to non-anaemic patients do anaemic patients have
1. higher all-cause mortality?
2. higher cancer recurrence?
3. higher rates of post-discharge complications – infections, acute kidney injury, cardiac events and delirium?
4. Higher rate of re-admission to hospital?
5. Reduced rate of chemotherapy?
6. Longer time between surgery and chemotherapy?
We will match cohorts by index year of surgery(±2 years), age(±2 years) and gender. We will adjust for year of surgery, age, gender, region, deprivation – practice level IMD, and anaemia at presentation.
We will use Cox proportional hazards regression for survival analysis to look at all-cause mortality and produce Kaplan–Meier curves to illustrate cancer recurrence. Rates of post-discharge complications will be analysed as a percentage of total discharges comparing anaemic and non-anaemic patients.
We are interested in comparing the outcomes in patients with anaemia and those without anaemia following their potentially curative resections for colorectal cancer.
Our primary outcomes are: all-cause mortality and cancer recurrence up to 5 years post-discharge.
Our secondary outcomes are: rates of post-operative complications – infections, acute kidney injury, cardiac events and delirium; rate of re-admission to hospital; rate of chemotherapy uptake; and time between surgery and chemotherapy. Rates of complications and readmissions will be assessed within the 3 month period post-discharge. Uptake of chemotherapy will be assessed within 6 months of diagnosis (without evidence (coding) for recurrent / metastatic disease).
Mortality data (all-cause mortality) and cancer recurrence (SNOMED-CT codes) will be obtained from CPRD.
Complications and readmission data will be obtained from HES. The ICD-10 codes are:
Complication Codes
N17 Acute Kidney Injury
I21 Myocardial infarction
J69.0 - aspiration pneumonia NOS
J13 – Pneumonia due to strep pneumonia
J14 - Pneumonia due to Hemophilus influenzae
J15 - Bacterial pneumonia, not elsewhere classified.
J18 –pneumonia (organism unspecified)
N390 Urinary Tract Infection
T814 Surgical site infection
T813 Wound infection
F05. Delirium
For chemotherapy we will use OPCS4 codes which are:
X35.2 Intravenous Chemotherapy
X38.4 Subcut chemotherapy
X70.1 Procurement of drugs for chemotherapy for neoplasm for regimens in Band 1
X70.2 Procurement of drugs for chemotherapy for neoplasm for regimens in Band 2
X70.3 Procurement of drugs for chemotherapy for neoplasm for regimens in Band 3
X70.4 Procurement of drugs for chemotherapy for neoplasm for regimens in Band 4
X70.5 Procurement of drugs for chemotherapy for neoplasm for regimens in Band 5
X70.8 Other specified procurement of drugs for chemotherapy for neoplasm in Bands 1-5
X70.9 Unspecified procurement of drugs for chemotherapy for neoplasm in Bands 1-5
X71.1 Procurement of drugs for chemotherapy for neoplasm for regimens in Band 6
X71.2 Procurement of drugs for chemotherapy for neoplasm for regimens in Band 7
X71.3 Procurement of drugs for chemotherapy for neoplasm for regimens in Band 8
X71.4 Procurement of drugs for chemotherapy for neoplasm for regimens in Band 9
X71.5 Procurement of drugs for chemotherapy for neoplasm for regimens in Band 10
X71.8 Other specified procurement of drugs for chemotherapy for neoplasm in Bands 6-10
X71.9 Unspecified procurement of drugs for chemotherapy for neoplasm in Bands 6-10
X72.1 Delivery of complex chemotherapy for neoplasm including prolonged infusional treatment at first attendance
X72.2 Delivery of complex parenteral chemotherapy for neoplasm at first attendance
X72.3 Delivery of simple parenteral chemotherapy for neoplasm at first attendance
X72.4 Delivery of subsequent element of cycle of chemotherapy for neoplasm
X72.8 Other specified delivery of chemotherapy for neoplasm
X72.9 Unspecified delivery of chemotherapy for neoplasm
X73.1 Delivery of exclusively oral chemotherapy for neoplasm
X73.8 Other specified delivery of oral chemotherapy for neoplasm
X73.9 Unspecified delivery of oral chemotherapy for neoplasm
We will use recurrent coding to assess cancer recurrence. Patients who were initially coded as having colorectal cancer and then subsequently have a further surgical resection, are coded as having recurrent / palliative disease, are referred to palliative care or after 6 months have chemotherapy (suggesting palliative chemotherapy rather than adjuvant chemotherapy) will be considered in the study to have cancer recurrence.
Philip Harvey - Chief Investigator - University of Birmingham
Alexandra Marley - Corresponding Applicant - University of Birmingham
Matthew Brookes - Collaborator - University of Birmingham
Nicola Adderley - Collaborator - University of Birmingham
HES Admitted Patient Care;Patient Level Index of Multiple Deprivation