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Protocols, Patient information sheets and consent forms

1. Protocols

The role of Positron Emission Tomography (PET) in the Pre operative Assessment of Colorectal Cancer

Research Protocol:

Pre operative assessment in patients with primary colorectal cancer

The objective is to determine whether pre operative investigation using FDG-PET ( 2- F18-fluoro-2-deoxy-D-glucose) gives superior information regarding extent of primary disease and distant spread when compared to spiral CT. If PET is shown to be superior in detecting micrometastasis then surgical management as well as pre and post operative adjuvant therapeutic strategies will be influenced.

Patients will be studied over a two year period and be recruited from the pool of patients referred to the Department of Surgery for treatment o f colorectal cancer. We aim to recruit 40 patients over the period of the study.

Inclusion criteria:

Confirmed diagnosis o f cancer o f the colon or rectum Cancer suitable for curative resection

Informed consent

Exclusion criteria:

Patients who are unable to give informed consent Patients who are unable to undergo PET scan

Each patient will undergo the following investigations: i) Spiral CT scan (abdomen & pelvis)

ii) FDG-PET scan (whole body)

Patients will have a spiral CT scan as part o f their routine investigation prior to admission to hospital for surgery and not more than four weeks previously. It is routine practice to perform spiral CT of the abdomen and pelvis as well as a chest x- ray. If a liver metastasis is found then spiral CT of the chest is performed. Patients are admitted to hospital two days before surgery so that they can undergo pre

anaesthetic assessment and bowel preparation. On the day before surgery patients will starve for a period o f four hours (and must not have intravenous glucose in any form). They will then be taken to the institute of Nuclear Medicine where they will be given an intravenous injection of radiolabelled glucose (FDG) through a cannula sited in an

arm vein prior to scanning. Following the injection o f FDG the patient will lie on a platform in the PET scanner. The scan information is acquired over the course o f an hour. The patient will then return to the ward and prepare for and proceed to surgery in the usual way. Full details o f history and examination will be available for

documentation as well as serum tumour markers, however, CT and PET scans will be reported blind and double read.

Information required from the CT scan and PET scan:

i) The position of the tumour ii) The size o f the tumour

iii) The extent of spread of the tumour -with particular note made of a) liver abnormalities b) suspected

lymphadenopathy CT’s will give the radiological TNM stage. Please refer to the two algorithms

attached. Treatment given will be routinely directed by the clinical findings and spiral CT. If an abnormality is found on PET and not on CT then in all cases a policy of observation will be adopted unless there is concurrence at laparotomy (for example, the detection of liver lesions) when appropriate biopsies and treatment will be initiated as standard practice in the Department of Surgery.

At Operation:

The operating surgeon will perform a thorough laparotomy and note the following: i) The position of the tumour

ii) The size o f the tumour

iii) The extent of spread o f the tumour -with particular note made of a) liver abnormalities b) suspected

lymphadenopathy

Surgery will be directed at the primary tumour and draining lymph nodes. If unexpected liver lesions are discovered appropriate biopsies and treatment will be initiated post operatively, once histology is available. The resected specimen will then have a fragment removed from the main cancer as well as from surrounding normal tissue (greater than 5cm away). The main specimen will be processed by the Histopathology Department.

Post operative surveillance:

Patients will be followed up as per the protocol in the Department o f Surgery. Over the period o f the study and for at least two years note will be made o f survival and recurrence rate.

Analysis:

Correlate: 1. Spiral CT and PET with each other and with operative findings. These results will then be related to the following.

1. Histological stage and grade 2. Tumour markers

3. Survival and recurrence

The role of Positron Emission Tomography (PET) in the follow u p of patients

with a history of colorectal carcinoma Research Protocol:

The objective is to assess whether FDG-PET (2-FI 8-fluoro-2-deoxy-D-glucose) is a more specific and sensitive method of following up patients who have been treated surgically for colorectal cancer than the methods currently available.

Patients will be studied over a period of two years fi’om those treated surgically for colorectal cancer in the Department o f Surgery. We aim to recruit 40 patients over two years.

Inclusion criteria:

Patients previously diagnosed with colorectal who have undergone operative treatment.

Full informed consent.

Exclusion criteria:

Patients who are unable to give informed consent Patients who are unable to undergo PET scan

Each patient will undergo the following investigations: i) Spiral CT scan every 6 months (abdomen) ii) FDG-PET scan every 6 months (Wiole body)

iii) Serum carcinoembryonic antigen (CEA) level measurement (every 3 months).

Patients who have undergone operative treatment for colorectal cancer will be followed up as per the Department of Surgery protocol (i & iii). In addition they will have an FDG-PET scan every 6 months over a two year period.

Full details of history and examination will be available for documentation as well as serum tumour markers, however, CT and PET scans will be reported blind and also double read.

If an abnormality is discovered on spiral CT or PET scan the patient will follow the algorithms attached. Treatment will be directed by clinical findings and CT scans. If there is an abnormality detected on PET but not on spiral CT a policy of observation with CT and PET will be followed. If PET is positive and CT equivocal then an alternative to imaging follow up will be a biopsy. Recurrences in the pelvis will be investigated by MRI if detected by PET or CT. If the recurrent cancer is amenable to operative treatment the patient will proceed to surgery and the steps outlined below will be followed. These cases should be in the minority. If an elevation is noted on routine CEA measurement the patient will undergo spiral CT and PET scan. They will then follow the algorithm for each imaging modality.

In some patients a biopsy may be offered if CT is equivocal and PET positive or if indicated under the normal policy of the Department o f Surgery on clinical grounds. If a patient declines a biopsy or is unable to have a biopsy performed then the patient will be treated on clinical grounds as determined by the multidisciplinary team as well as being followed up with 6 monthly spiral CT and FDG-PET.

Information required from spiral CT and FDG-PET:

i) The position of the recurrence ii) The size o f the recurrence

iii) The extent of spread of the tumour -with particular note made of a) liver abnormalities b) suspected

lymphadenopathy

CT criteria for métastasés are : Typical appearance Growth on CT Concordance

If a patient does proceed to surgery they will undergo the following steps:

At Operation:

The operating surgeon will perform a thorough laparotomy and note the following: i) The position of the tumour

ii) The size o f the tumour

iii) The extent o f spread o f the tumour -with particular note made of a) liver abnormahties b) local spread

The resected specimen will then have a fragment removed from the main cancer as well as from surrounding normal tissue (greater than 5 cm away). The main specimen will be processed by the Histopathology Department.

Post operative surveillance:

Patients will be followed up as per the protocol in the Department o f Surgery. Over the period o f the study and for at least two years note will be made of survival and recurrence rate.

Analysis:

Correlate: 1. Spiral CT and PET with each other 2. CT and PET with levels of CEA. 3. The above with survival and recurrence