A heavyweight machine worth RM14 million has spelt the end to cancer tumours' 'hide-and-seek' games, writes CHAI MEI LING.

Dr G. Selvaratnam, NCI Cancer Hospital's head of oncology & radiation therapy.

Brightly coloured and three-dimensional scans allow doctors and medical physicists to get a clearer view of the tumour, highlighted here as yellow in a head-and-neck case.

PUT in the eyes. Take out the spinal cord. Rotate his head. For cancer specialist Dr G. Selvaratnam and his team of medical experts, these are daily preoccupations.

They twist and turn a patient's vital organs, studying the whole make-up from every imaginable direction to pinpoint the exact location of cancer cells.

It's a procedure even the faint-hearted would appreciate because it's done virtually.

The gadget which makes this and much more possible, is the RM14-million Trilogy Linear Accelerator (TLA) , which sits behind six-inch walls in the NCI Cancer Hospital in Nilai, Negri Sembilan.
The is basically a radiotherapy tool which dispenses radiation dosage to cancer patients at specified areas to kill off tumour cells.

The TLA is a fantastic machine, staff at the NCI say. Just a few year ago, radiotherapy machines couldn't give three-dimensional views of body parts affected by tumours.

"Previously, we roughly knew (from scans) the whereabouts of neck and tumour. But with the TLA, everything is in real perspective. Anatomical margin size and relationship mirrors that of real life," says Dr Selvaratnam.

Pointing to a scan of a male patient, he says: "That is a man, in every detail. You can't get more detailed than that. You can actually see the little scars."

Thre TLA can show the most minute feature of any anatomical structure down to the nerves and blood vessels. It enables three-dimensional computed tomography (CT) scans to be rotated in any way, and in the process, organs like the heart, lungs, and liver, and the spinal cord can be contoured, with their images plastered on screen.

In the case of the male patient with a typical head and neck tumour, his spinal cord had been contoured in an image.

At the click of a button, the TLA highlighted the cancerous areas in a bright colour. It also showed how the tumour looked in relation to the spinal cord.

Oncologists and medical physicists studying the images now know not only the tumour's location, but how close it was to other vital organs.

This latter piece of information is vital, because, when administering radiation dosage on the cancer cells, the radiologists have to be careful not to allow too high a dose on surrounding critical organs.

All organs have a certain tolerance towards radiation, says senior medical physicist, M. Kala Krishnan.

"If you exceed that, you're going to impair the structures. And once given, it's irreversible. There's nothing you can do to take back the dose or use some medication to counter it,"

So what happens when there's an overdose?

"There should be no overdose," Kala states firmly.

Here's where another factor of the TLA comes into play. One of its methods of treatment - the intensity modulated radiotherapy (IMRT) - can deliver radiation doses accurately.

When the radiation system scans a body part, it targets the cancerous area and applies more dosage there, but when it comes to normal tissues, the beam intensity decreases.

"The idea is to keep the dose very concentrated on the tumour, and immediately after that, the dose must fall off. From 100 to 0 per cent as quickly as possible," says Dr Selvaratnam, the hospital's head of oncology and radiation therapy.

TLA is programmed to tackle even the most vulnerable of cases, such as when the tumour is wrapped around a critical structure like the spinal cord, a major organ or blood vessel.

This versatility in radiation targeting and better protection of normal tissues has seen the risks of side effects slashed by quite a considerable amount.

Occurrence of pain and ulcers in the mouth, a common side effect for head and neck cancer patients, can be lowered by 30 to 40 per cent, while dryness of mouth be reduced by as much as 50 per cent.

"It hasn't been proven, but hopefully, lowering the side effects will translate to better outcome, less complications, and higher survival rate," says Dr Selvaratnam.

Before the 1990s, when IMRT wasn't in use yet, the conventional radiotherapy could be likened to a "blunderbuss treatment".

There was no such thing as zooming in on cancer areas and customising radiation dose. The conventional method was opening the treatment area in square fields and applying a flat dose through.

And because the vital organs are subjected to the same amount of radiation as the tumour, some doctors found themselves caught between the devil and the deep blue sea.

They could only choose between a high dosage which kills off the cancer but impairs healthy tissues, or a low dose which keeps healthy organs safe, but doesn't eliminate tumours.

More often than not, the doctors would opt for the low dose.

"Doctors would stick to the dose, increasing it until it reaches the maximum level, and then reducing it because they know the spinal cord can't take it anymore. They have no choice; they cannot take the risk of paralysing the patient," says Kala.

It's interesting to note that radiation has not changed in any way since the days radiotherapy had been in use as a treatment for cancer more than 100 years ago.

What has changed, though, is the delivery system, which allows the control of radiation.

Technology advancement has improved treatment, but not in lightening the responsibility and workload of medical staff.

TLA is an amazing equipment, which requires tedious preparation work before each session.

Before treatment can occur, consultation, simulation, planning and quality assurance must first take place in NCI.

"We plan, plan and plan again until we get the best dose distributions that we think best fits the patient," says Dr Selvaratnam.

If the dosage delivery does not match the planned dose influence map by 99.9 per cent, the staff redo the whole process.

NCI purchased TLA in 2006. Within a year, it was marketed by Varian Medical Systems, making the hospital the first in South Asia and the ninth in the world to have it.

Today, more than 400 patients have been treated using TLA, with more than 180 undergoing IMRT.

The total cost of treatment per person ranges from RM5,000 to RM45,000.

'Master' gene that alters tumours

GENETICISTS have identified a super gene which causes breast cancer to metastasise, the process by which the disease spreads to other organs.

Described as a "master regulator", the SATB1 gene alters the behaviour of at least 1,000 other genes within tumour cells.

When over-activated, the gene makes cancer cells proliferate, and when neutralised, it stops the cells from dividing and migrating.

The findings could not only pave the way to diagnostic tools that show the likelihood of the disease spreading but to drugs that could prevent or treat metastasis in breast cancer as well, Termumi Kohwi-Shigematsu of the Lawrence Berkeley National Laboratory in Berkeley, California, said.

Up to now, it was impossible to predict whether cancer cells in a tumour were destined to invade neighbouring tissue, travel through the blood system and form secondary tumours elsewhere in the body. But the SATB1 protein is just such a marker. A tumour in which it is activated "is destined to metastasise", she said.

Metastasis is the overwhelming cause of death in patients with solid tumours. Less than 10 per cent of women with metastatic breast cancer survive beyond a decade, and just over a quarter make it past five years.

SATB1's normal role in organising other genes was already well known, thanks in part to pioneering research by Kohwi-Shigematsu in the 1990s.

But the new study is the first to establish that "SATB1 is both necessary and sufficient for breast cancer cells to become metastatic", she said.

In experiments on mice, the scientists "knocked down", or deactivated, the SATB1 gene by removing certain RNAs in the tumour cells upon which the gene depends for multiplying.

The results were dramatic.

Between 125 and 160 metastatic nodules formed in each lung of all the control mice. But in the rodents in which SATB1 was suppressed, the number was between zero and five.