Symptoms: symptoms started with slight double vision (Diplopia) and headaches (cephalgia). Her symptoms progressed to severe double vision, where her right eye remained in the central position when she looked right. Prior to surgery her eyelid had almost closed and the headaches were severe. Her colour (skin) had become quite pale. There were some days where she could hardly get out of bed. She would get up in the morning, have some breakfast, go back to bed and sleep. This was really worrying.
After initial investigation it was thought that she had a pituarity tumour.
All these symptoms were all due to tumour growth, pressing on the optic nerves and surrounding the pituarity gland. Giant cell tumours have a tendency to push away vascular structures and not encase them.
Treatment: The current opinion in most cases is to surgically remove as much of the tumour as possible, due to the location and surrounding structures it can be among the most complex and difficult procedures in skull-base surgery. Radical surgical resection is attempted when possible, as these tumours have a high incidence of recurrence if incompletely removed. Where it is not possible to remove all of the tumour, the residual tumour must be treated with adjuvant therapy.
MRI remains the diagnostic investigation of choice.
Surgery: Both operations and biopsy were done using the transphenoidal approach, through the nose. This approach seems to be less invasive and more cosmetically pleasing, the recovery time appears to be shorter than other more radical procedures. Two surgical procedures. Reason being, her symptoms returned two weeks after the first procedure. After an MRI scan her neurosurgeon discovered the tumour had grown back to it’s original size and subsequently the symptoms.
There is an incision made inside one of her nostrils, because she is young and small, the cut went down and around the bottom corner of her nose. They then drill through the bone behind this. This then allows them access to important structure called the cavernous sinus. The carotid artery runs through the middle of this. Damage to the carotid artery will produce a bad stroke, so must be avoided.
Multiple nerves also runs through it, taking sensation from the face, and taking messages to the muscles around the eye, and eyelid. The tools they use include high powered operating microscopes and rigid fiberoptic endoscopes. The operating microscope allows “binocular” vision with high quality optics. Once the operation is complete, the inside is closed and packed surgical sponges are inserted in both nostrils. As I said earlier she had a few stitches at the bottom corner of her nose.
Radiotherapy: External radiotherapy uses high energy X-ray beams. These beams are directed at the tumour from a machine outside the body. The radiotherapy beams destroy the tumour cells in the treatment area. Normal cells are also affected but they are better at repairing themselves than cancer cells.
The patient must not move during treatment, therefore a mask is normally made. This is usually a soft sheet of plastic formed over the patients head and allowed to set. The mask is fitted over the patient then it is attached to the table, immobilising the treatment area. The marks on the mask allow the radiographers to accurately line up the machine.
Denosumab and the magic bullet
Giant cell tumours are rich in Osteoclast cells and contain mononuclear cells that produce rank ligand (RANKL). RANKL seems to play a big part in the formation and activation of the osteoclast (giant cells) which are responsible for the bone destruction seen in giant cell tumours.
Denosumab is a fully human monoclonal antibody that specifically targets a ligand known as RANKL. Given almost any substance, it is possible to create monoclonal antibodies that specifically bind to that substance; they can then detect or kill that substance.
Magic bullet: The idea of a magic bullet was first introduced by Paul Ehrlich at the beginning of the 20th century. He proposed that, if a drug could be made that attacked tumour producing cells, then a toxin for these cells could be delivered along with the agent of attacking these cells and not others.
Rachael has been a participant in Amgen’s Phase 2 clinical trial of Denosumab since May 2010.
Although this drug has been released for the use in the treatment of severe osteoporosis, it has not yet been approved for the treatment of Giant Cell Tumours.
To date Rachael has had 8 injections of Denosumab, each of 120mg. After her fifth injection she was scanned to check the effectiveness of the drug. The scan revealed that her tumour had shrunk by 1.4cm and was showing signs of death. This was quite amazing, considering that two operations, radiotherapy and bisphosphonate infusions had done nothing to halt this tumour from growing.
Rachael has her injection monthly in her stomach. The injection is subcutaneous, under the skin. She also takes calcium and vitaminD daily this is also part of the trial along with the drug. The only side effects she has had is an upset stomach, which she tolerates well. The trial team seem to think it is the calcium and vitaminD that causes this and not the drug.
