Treating liver cancer

Treating liver cancer

Despite the increasing availability of cancer treatments in hospitals worldwide, liver cancer remains one of the more difficult cancers to treat.

Regardless of its origins (whether it starts in the liver, or is a cancer that has spread to the liver), in a lot of cases, conventional therapies like surgery, systemic chemotherapy, and external radiotherapy, are not suitable treatments.

Systemic chemotherapy - the consumption or injection of anti-cancer drugs that travel through the whole body - often does not work well for liver cancer.

External radiotherapy, on the other hand, is not suitable because normal liver cells and the organs surrounding the liver are very sensitive to radiation.

Finally, surgery, the only method that has the potential to "cure" liver cancer by removing it, can only be done for an estimated 10 to 30% of patients because it is only suitable for those who have relatively good liver function with small tumours located within the liver.

"When patients can go for surgery for liver cancer, it really confers long-term survival," says Singapore General Hospital head of the hepato-pancreatobiliary surgery team Prof Pierce Chow. "But the thing with most liver cancer patients is that although surgery is very good, when they are diagnosed with this cancer, they are already at the stage of the disease where surgery is not possible."

However, not all is lost. As doctors and scientists work to overcome the challenges involved in treating liver cancer, more treatment modalities are starting to emerge as viable therapies.

Instead of "poisoning" cancer cells with systemic chemotherapy, or "burning" them with external radiation, doctors can now inject cancer-destroying agents directly into the liver through the arteries that supply blood to it. These agents work by either killing the cancer cells or blocking and destroying the arteries - the blood vessels that nourish them (see Treatment options).

One of these therapies is radioembolisation (RE), or Selective Internal Radiation Therapy (SIRT).

In SIRT, interventional radiologists (doctors who specialise in radiology) will pass a catheter through an artery near their patient's groin to reach the small blood vessels (arterioles) that supply tumours in the liver. Once the catheter reaches the arterioles that feed the tumours, the doctors will release radioactive beads (called microspheres) into them.

While the microspheres can pass through the arterioles, they are too large to pass through the capillaries that come after the arterioles. These microspheres will then lodge in the arterioles, where the radioactive material in the beads (like Yttrium-90) release a high dose of radiation over time and kill the surrounding cancer cells.

Although the technology has already been researched and developed in the 1980s, it has only gained increasing clinical interest in the past decade.

"In the 1980's and 1990's, studies were done on animals to make sure the treatment is safe," says one of the researchers of the technology, professor of surgery at The Chinese University of Hong Kong medical faculty, Prof Joseph Lau. After that, studies on its safety and appropriate dose ensued.

Since 2000, it has been used in patients who have failed other therapies. In Malaysia, it has been available since 2007.

Prof Lau and Prof Chow were speaking at a press conference called by Sirtex, an Australian based medical device company that produces the tiny radioactive microspheres used in SIRT, at the sidelines of the recent fifth annual conference of the International Liver Cancer Association in Hong Kong.

Together with Taipei Veterans General Hospital attending physician in radiology Dr Rheun-Chuan Lee, and University of Navarra School of Medicine professor of medicine Prof Bruno Sangro, they were there to present some of their experience and latest findings on SIRT.

Prof Sangro, who conducted a retrospective study that evaluates the medical records of 325 patients in eight centres across Europe, found that the treatment was reasonably well tolerated. Some of the side effects include fatigue (in 54% of patients), nausea or vomiting (32%), abdominal pain (27%) and fever (12%).

In his study, about half the patients - who are mostly male (81%), ranging from 22 years old to 87 years old, with liver cancer from the early stages to the advanced and terminal stages - survived more than 13 months after the treatment.

About 16% of them lived up to three years after.

"The main factors that influence the survival of a patient, is the liver function before the treatment, and also how advanced and aggressive the tumour was," says Prof Sangro. In other words, a patient's prognosis is worse if they have more tumour or tumours that have spread, poor general health, or liver dysfunction before the treatment.

Prof Sangro's study, called the ENRY (European Network on Radioembolisation with Yttrium-90 Resin Microspheres) study, is one of the largest studies published on the treatment to date.

Despite some studies that find the median overall survival of patients treated with SIRT comparable to those treated with conventional therapies like transarterial chemoembolisation (TACE) and radiofrequency ablation (RFA), many doctors are still turning to it when these treatments fail, or are not suitable.

This is partly due to cost considerations and the lack of data to show that it could be used as a first-line treatment.

In Taiwan, SIRT is only used when the patient's tumour invades the main blood supply of the liver (the portal vein) or does not respond to conventional therapies like TACE because SIRT is not covered under the national health insurance in the country.

Says Dr Lee, patients who are treated with TACE need more sessions of treatment (about three to six sessions) compared to SIRT (usually only once), and patients treated with SIRT tend to have less post-embolisation syndrome (like nausea or vomiting, fatigue, abdominal pain). However, he reckons that SIRT is a much more complex procedure.

To find out whether SIRT can be used as a first-line treatment for patients with advanced liver cancer who have failed conventional therapies, Prof Chow is now part of an Asia Pacific phase III randomised controlled trial to compare SIRT with sorafenib, an oral drug used to treat patients with advanced liver cancer who have failed conventional therapies.

"At the end of the trial, we will be able to see which of these two therapies should be used as a first-line therapy for these patients," says Prof Chow.

Like many cancer treatments, SIRT is not suitable for everyone. Commenting on the press conference, Dr R. Kananathan, a Malaysian consultant oncologist in private practice reckons that a patient's laboratory results need to show that they have relatively good liver function and general health to ensure that it is safe to perform the procedure.

After that, interventional radiologists will need to perform a special scan using radioactive material to determine the amount of radiation that is likely to pass through the liver to the lungs ("shunting") before radioactive microspheres can be delivered into a patient's liver.

They will proceed only if the amount of radiation that has passed through is less than 15%, says Dr Kananathan.

Back in Kuala Lumpur, Fit4Life asked consultant vascular and interventional radiologist Dr Alex Tang for some comments on the procedure. Dr Tang says that while SIRT is very useful in large or multiple small hepatomas (liver tumours) in the intermediate or advanced stages (that are limited to one or two lobes of the liver), it does come with "a lot of catches".

Besides the cost factor, it is also a very technically challenging procedure and errors can bring about serious complications.

That being said, Dr Tang does not view the procedure as a last resort when all else fails. "I'd say we should offer the procedure before the liver is too weak," he says.

However, a patient has to be assessed carefully in terms of his or her clinical status, disease status, and financial status, as well as the possible clinical outcomes and complications before the best option is suggested.












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