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Tuesday, January 3, 2017

Radiation Therapy For Breast Cancer

    Radiation Therapy For Breast Cancer - Developments in anaesthesia and better control of surgical infections and bleeding at the turn of the 20th century encouraged the practice of radical surgery for breast cancer in the United States.

The disfiguring Halstead radical mastectomy was a popular choice until the 1970s.

Breast conserving surgery (BCS) was not a common procedure then.

Evolution of breast cancer therapy

In Britain, a report on 250 patients treated with BCS dates back to 1937 in the British Medical Journal.

Dr Geoffrey Keynes was a surgeon and proponent of BCS and radiation treatment.

He had observed outstanding three-year and five-year survival rates for patients whose tumour were confined to the breast and who had undergone BCS.

For more advanced breast cancers, he also observed the regression of tumour with radiation therapy.

In the 1940s, he was able to show with his series of data on 600 patients who had BCS and radiotherapy, that these patients had similar survival rates to patients who had undergone radical breast mastectomy.

In Europe, the conservative treatment with radiation practice began to spread. However, in the US at that time, more radical surgery was the treatment of choice.

In the 1970s, American scientist and surgeon Dr Bernard Fisher led a randomised controlled trial to test the efficacy of lumpectomy (BCS) versus lumpectomy and radiation (better known as breast conserving therapy, BCT) versus mastectomy.

In all three arms of the study, the patients received axillary node dissection.

He found that survival rates were similar in the last two groups, though local recurrence of the tumour was more common in the BCT group.

This landmark study provided evidence that conservative treatments are equal to mastectomy.

Consequently, radiotherapy became the mainstay of BCS treatments in the US.

More recent data from long-term cohort observational studies showed local recurrence to be similar in both groups, even after adjusting for stage of disease.

Radiation is traditionally given externally to the breast. This is known as external beam radiotherapy (EBRT).

It is usually carried out for about three to six weeks after surgery if chemotherapy is not required.

If chemotherapy is required, it is given for about five months, followed by radiotherapy.

The radiation is given in many fractions, most commonly 15, with an eight fraction boost to the tumour bed, giving a total of 23 fractions for those who undergo BCS.

Hence, daily visits to the hospital can be between three and five weeks.

Intraoperative radiation therapy

The evolution of EBRT to reduce the risk of complications like radio-necrosis and exposure to the lungs and heart, has brought about modern machines with lower side effects.

While the era of Dr Keynes in the 1940s saw radiation therapy from radium crystals, the latest EBRT uses linear accelerators that allows radiation to be targeted directly at the tumour bed during surgery itself.

This innovation, known by the acronym Targit (Targeted Intraoperative Radio-therapy), originated in University College London and was pioneered by Prof Dr Jayant Vaidya, Prof Dr Michael Baum and Prof Dr Jeffrey Tobias in 1998.

Intraoperative radiotherapy is given at the time of lumpectomy.

Radiation is given directly into the lumpectomy cavity using a special spherical applicator.

The doses are concentrated within 1cm from the surface of the applicator.


After 30 to 50 minutes of radiation, depending on the size of the cavity, the surgery is completed, the patient wakes up and returns to the ward.

A large multicentre randomised controlled study from 33 centres in 11 countries involving 3,451 women called the Targit A study was published in medical journal The Lancet in 2013, and it showed that Targit using an adaptive approach with the Intrabeam system in low risk breast cancer patients was as effective as EBRT.

Low risk breast cancer patients include those with Grade 1 or 2 tumours, those who are oestrogen receptor-positive and lymph node-negative.

The adapted approach means that patients who show any high risk features like lymph node involvement, will require EBRT.

image: http://www1.star2.com/wp-content/uploads/2016/10/sfit_fitbreast2310_py_2.jpg

The intrabeam system provides radiation treatment targeted at the tumour bed.
The intrabeam system provides radiation treatment targeted at the tumour bed.

The mastectomy option

Despite this changing evidence of safety in BCT, women still opt for mastectomy for a variety of reasons.

These include concern about cancer remnants in the breast and lack of access to radiotherapy, especially if they live far away from cities with radiotherapy services.

In Malaysia, the reach of radiotherapy services is limited, especially on the east coast of Peninsula Malaysia, Sabah and Sarawak, making it inconvenient to travel, especially as it takes three to five weeks of daily radiation treatment.

Compounding this further, the size of tumour detected at diagnosis is usually large due to low mammogram screening practices within the community.

Malaysia does not have population- based mammographic screening.

And opportunistic mammographic screening, where patients go on their own or are advised to by their doctors, is sporadic.

The rates of BCT in Malaysia range from 5% to 25%, depending on locality. We still face a huge mastectomy rate due to late presentation and lack of access to radiotherapy.

Breast cancer treatment is multimodular and a lengthy process, with some therapies requiring three to five treatments – namely, surgery, chemotherapy, radiotherapy, hormonal therapy and targeted therapy.

There is also a sixth form of treatment: immune therapy.

Hence, treatments can be protracted and require travel, as well as time off work, which requires a lot of social and financial support.

Weighing the advantages

Intraoperative radiotherapy provides multiple advantages.

In a low risk patient, it would be a single dose in the operating theatre.

Those with adapted risk would require an additional 15 fractions of EBRT, compared to 23 fractions.

Many systems are available worldwide. In Malaysia, the Intrabeam system, which has been studied extensively for good prognosis patients, is available.

Intraoperative radiotherapy using the Intrabeam system allows not only shortened treatment time, but also provides immediate radiation as it is given at the time of surgery.

Studies have shown this gives better outcomes compared to delayed radiotherapy.

In addition, there is greater accuracy in targeting the tumour bed, thus avoiding geographical misses of the shifting tumour bed after the wound is closed and healed for a patient who needs external beam radiotherapy.

Due to the shallow depth of the radiation, less radiotherapy side effects are expected, especially to the region of the ribs, heart and lungs.

This service requires a multidisciplinary approach requiring a diverse team of breast surgeons, oncologists, physicists, breast care experts and operating theatre nurses, who collaboratively address the care of the patient and special issues related to intraoperative radiotherapy, like radiation safety, dosimetry, sterilisation and care of the equipment.

University Malaya Medical Centre (UMMC) will soon be participating in a worldwide clinical trial looking at using this technique in high risk breast cancer patients, which will allow more women to have intraoperative radiotherapy as a radiation boost, and hence, shortening the need for EBRT from five to only three weeks.




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