A Prospective Randomised Trial of Sentinel Node Biopsy for High Risk Non-Melanoma Skin

A PROSPECTIVE RANDOMISED TRIAL OF SENTINEL NODE BIOPSY FOR HIGH RISK NON-MELANOMA SKIN CANCER (SNIC TRIAL)

Sentinel node biopsy or observation

INFORMATION FOR PARTICIPANTS

Introduction

You are invited to take part in a research study which will investigate whether in your type of skin cancer early detection and treatment of very small lymph node metastases is useful. It will be compared to the current wait-and–see approach, in which the tumour is removed and the local lymph nodes are not checked during the operation. The type of skin cancer you have will spread (metastasise) to lymph nodes in approximately 2 out of 10 patients. If this happens, the metastases are usually detected when they are large, leading to a major operation to remove them. In addition, in case of nodal metastases, there is a 30% chance that the disease will spread further and that a cure will be less likely.

In this study we would like to find out if an examination of the nodes that directly drain the tumour (sentinel nodes) for small tumour metastases is useful. The idea behind early detection and treatment of these metastases is that it might improve the chances of controlling the disease in an early phase. In addition, we believe that the operation to remove small nodal metastases will have less impact on you and will involve fewer complications compared to an operation performed for larger metastases later on.

The study is being conducted within this institution by surgeons who specialise in treating skin cancers:

• Dr Jonathan Clark, Consultant in Head and Neck Surgery at Royal Prince Alfred Hospital, Liverpool Hospital and St George Private Hospital.
• Dr Bruce Ashford, Consultant in Head and Neck Surgery at Liverpool Hospital, St George Private Hospital and Wollongong Hospital.

The study is part of an international collaboration coordinated by Australian, New Zealand, Canadian and Dutch researchers.

Study Procedures

If you agree to participate in this study, you will be asked to sign the Participant Consent Form. You will then be randomly assigned (like the toss of a coin) by the central study committee to receive either the current standard treatment, or the standard treatment and removal and examination of your sentinel lymph nodes. Your local doctor cannot influence this. Both treatments are considered to be good options by the international surgical community. Our aim is to find out if the combination of removal of the skin tumour together with sentinel node biopsy is better.

The standard treatment consists of removal of the skin tumour and appropriate closure of the skin. After the operation, you will be monitored by your doctor every 4 months during the first 2 years, and every 6 months up to 5 years after the operation. At these check ups, an ultrasound will be performed to examine the lymph nodes in the area that receives drainage from the original tumour site. If there is suspicion of metastases in those lymph nodes, this will be examined by a needle biopsy. If there are metastases, you will be scheduled for an operation in which the lymph nodes with the metastases and the surrounding lymph nodes in that area are removed.

If you are assigned to standard treatment plus biopsy and additional examination of the sentinel nodes, you will be asked to undergo a scintigraphy on the day or morning before the operation. This investigation helps us to find the sentinel nodes. In scintigraphy you will have an injection of a minimally radioactive substance around the tumour. This substance will migrate from the tumour to the sentinel nodes, which can be detected by scanning for the radioactive signal. The staff at the Department of Nuclear Medicine where the scintigraphy takes place will mark the skin overlying the sentinel nodes so that the surgeon knows where to look for the sentinel node. During the operation (when you are anaesthetised) the surgeon will inject a blue dye which also helps to detect the sentinel nodes. The sentinel nodes will be removed through a small skin incision at the same time as your skin tumour is removed. After the operation you will be notified of the pathology results of the sentinel nodes. If they contain metastases, we know that there is a chance that the other nodes at the same location also contain metastases. Therefore, you will then be scheduled for a second operation in which the other lymph nodes in the same area as the sentinel nodes will be removed as well.

You will be asked to fill out a list with questions concerning your quality of life. This will take less than 10 minutes. This list will be given to you before the operation and yearly thereafter.

The researchers would like to have access to your medical record and pathology results to obtain information relevant to this study. In addition, a sample of your skin tumour will be kept for future studies to find out if the genes in the primary tumour can predict the occurrence of nodal metastases. This is a sample that would normally be discarded.

Risks

All medical procedures - whether for diagnosis or treatment, routine or experimental – involve some risk of injury. In addition, there may be risks associated with this study that are presently unknown and unforeseeable. In spite of all precautions, you might develop medical complications from participating in this study.

The possible risks of participating in this study can actually be separated into discomforts and risks.

The discomfort related to the biopsy is the injection with a radioactive substance for scintigraphy. This may cause local pain at the injection site. The scintigraphy during this research study involves exposure to a very small amount of radiation. As part of everyday living, everyone is exposed to naturally occurring background radiation and receives a dose of about 2 to 3 millisieverts (mSv) each year. The effective dose from this study is about 0.02 mSv. At this dose level, no harmful effects of radiation have been demonstrated and the risk is negligible. This radioactive dose is actually much lower than the amount you are exposed to during long distance flights or CT-scans and is comparable to that received from routine diagnostic X-ray examinations.

The risks of the sentinel node biopsy are related to injection of blue dye and the operation that will be done to perform the lymph node biopsy. The biopsy is a small procedure. The risks of this procedure are wound infection (experienced by less than 1% of patients) and nerve injury at the biopsy site (experienced by less than 0.5% of patients). Because of the blue dye injections for lymphatic mapping, your urine and stool may be discoloured for 24 to 48 hours after surgery. About 0.4% of patients demonstrate allergic reactions to the blue dye, varying from local irritation at the injection site to the development of blue hives scattered over the whole body. These can be treated by antihistamines and/or corticosteroids in case of mild symptoms. In 0.03% of patients a more severe, anaphylactic reaction occurs, requiring intravenous injection of medication to suppress the reaction and support blood pressure and breathing. Sometimes mechanical ventilation is necessary in those cases. In the rare circumstance that this happens to you, the surgeon and anaesthetist in the operating room will always be prepared to perform emergency resuscitation, which is quickly available because you will be in the controlled environment of the operating room. With the current available treatments, recovery after allergic reactions will be complete in almost all patients. As a comparison, the rate of people allergic to antibiotics is 1-5%, of which 30% might get the severe reaction requiring intravenous medication. This is 10 times higher than the allergy rate for blue dye.

It is important that women participating in this study are not pregnant and do not become pregnant before the operation. If you are a woman of child-bearing potential and there is any possibility that you are pregnant, the researchers will perform a pregnancy (urine) test before you start in the study

Benefits

While we intend that this research study furthers medical knowledge and may improve treatment of patients with skin cancer in the future, it will probably not be of direct benefit to you.

Compensation for injuries or complications

If you suffer any injuries or complications as a result of this study, you should contact the study doctor as soon as possible, who will assist you in arranging appropriate medical treatment. If you are eligible for Medicare, you can receive any medical treatment required to treat the injury or complication, free of charge, as a public patient in any Australian public hospital.

In addition, you may have a right to take legal action to obtain compensation for any injuries or complications resulting from the study. Compensation may be available if your injury or complication is sufficiently serious and is caused by unsafe drugs or equipment, or by the negligence of one of the parties involved in the study (for example, the researcher, the hospital, or the treating doctor). You do not give up any legal rights to compensation by participating in this study.

Costs

Participation in this study will not cost you anything, nor will you be paid.

Voluntary Participation

Participation in this study is entirely voluntary. You do not have to take part in it. If you do take part, you can withdraw at any time without having to give a reason. Whatever your decision, please be assured that it will not affect your medical treatment or your relationship with the staff who are caring for you.

Confidentiality

All the information collected from you for the study will be treated confidentially, and only the researchers named above and other medical staff related to the study will have access to it. The study results may be presented at a conference or in a scientific publication, but individual participants will not be identifiable in such a presentation.

Further Information

When you have read this information, your local doctor or the surgeon will discuss it with you further and answer any questions you may have. If you would like to know more at any stage, please feel free to contact your local doctor, or Dr Clark at 02 9822 5033, Dr Ashford at 0242266111 or Dr Kelder, fellow in Head and Neck Surgery and associate researcher in this study at 02 9515 7535.

This information sheet is for you to keep.

Ethics Approval and Complaints

This study has been approved by the Ethics Review Committee (RPAH Zone) of the Sydney South West Area Health Service. Any person with concerns or complaints about the conduct of this study should contact the Executive Officer on 02 9515 6766 and quote protocol number X09-0325.

The conduct of this study at the Liverpool Hospital has been authorised by the Sydney South West Area Health Service. Any person with concerns or complaints about the conduct of this study may also contact the Research Governance Officer on 02 9612 0614 and quote protocol number X09-0325.

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MASTER Version 3, 25 February 2010

Liverpool Version 1, 25 February 2010