Single-dose radiotherapy as effective against breast cancer as radiation

Women operated for removing breast cancer tumour are usually given radiation radiotherapy to kill any lurking cancer cells after surgery. Usually, radiation therapy lasts for three to five times a week, for about 3 to 5 weeks. A novel, single-shot radiotherapy, that too administered immediately after the surgery, a recent study finds, is as effective as conventional radiotherapy for most women. The researchers say “this approach has many advantages for the patient, such as less travelling for treatment, improved quality of life, and fewer side effects. Another important advantage is the major cost savings for the health services.”

TARGIT-IORT

Targeted Intraoperative Radiotherapy (TARGIT-IORT), a novel breast cancer treatment, is increasingly available throughout the world. The long-term effectiveness is confirmed by the randomised study conducted on 2298 women aged 45 years and older, suffering from breast cancer. The study was conducted across 32 centres in 10 countries, including UK, France, Germany, Italy, Norway, Poland, Switzerland, United States, Canada and Australia,  published in the recent issue of the prestigious British Medical Journal.

Why radiotherapy?

Earlier, oncologists had no option but to remove the whole breast when cancer tumour is detected. However, if the cancer is detected early enough, it can be treated with lumpectomy, that is breast-conserving surgery. If the cancer is detected at an advance stage, mastectomy, which is the removal of the whole breast, is the only option. With advanced imaging technology nowadays, the surgeon can locate the lump of the cancerous tumour. However, even after surgery, few cells may remain in the periphery, which may grow and relapse again. Radiation therapy is recommended to destroy any leftover cancer cells in the breast after the tumour is removed.

“Radiation therapy is an advanced therapy and now a days it is used for most of the cancer forms. It kills or damage the DNA of cancer cells so that they die or stop dividing,” said Dr. Pawan Gupta, Oncologist, Max Hospital, Patparganj, New Delhi.

Although microscopic cancer foci may exist in other parts, most of the reoccurrence of breast cancer was near the primary tumour site. An effective cleansing cancer cell from the site of surgical removal is imperative to prevent a recurrence.

Novel radiotherapy 

Until now, the external beam radiation therapy (EBRT) was administered to kill the surviving cancer cells. It is administered to the whole breast. In each session, the administration of radiation last only for a few minutes, however, the therapy has to be given for a period of three to six weeks, from three to seven days a week. In short, patients will require about 15 to 30 hospital visits, which could be a significant distance from where the patient lives. Fearing the logistical issues of conventional radiotherapy, even when breast preserving surgery is feasible,  often the patients are obliged to choose mastectomy.

In the game-changing ‘Targeted intra-operative radiotherapy’ in short TARGIT-IORT, a ball-shaped device capable of providing radiation therapy is placed immediately after the surgery, even while the patient is in the operation table under the anaesthesia. The radiation is ‘targeted’ as the device is placed in the cavity resulting from the removed tumour. It is directly administered to the region where cancer had been. This single-dose radiation treatment lasts for about 20 to 30 minutes. Except in certain exceptional cases, most patients need not make extra hospital visits, benefiting both patient safety and well-being.

Lead author, Indian-origin expert Professor Jayant Vaidya, (Professor of Surgery and Oncology, UCL Surgery & Interventional Science), said: “With TARGIT-IORT, women can have their surgery and radiation treatment for breast cancer all at the same time. This reduces the amount of time spent in hospital and enables women to recover more quickly, meaning they can get back to their lives more quickly.”

Breast cancer burden

Two million women were diagnosed worldwide with breast cancer in 2018 all over the world. Of which, unfortunately, 6,26,000 died, many due to late detection of cancer. In India, the 2018 report of Breast Cancer statistics recorded 1, 62,468 new registered cases and 87,090 reported deaths. More than 50% of Indian women suffer from stage 3 and 4 of breast cancer when the mastectomy that is whole breast removal is the only option. If only the breast cancer is detected early enough, avoidable deaths can be prevented and a large number of women saved.

The TARGIT-IORT technique was developed by clinical academics, Professors Vaidya, Tobias and Baum, in 1998 in collaboration with the manufacturers, Carl Zeiss, Germany. The instrument called ‘Intrabeam’ is a miniature and mobile X-ray source which emits low energy X-ray radiation. The relative biological effectiveness (RBE) of soft X-ray radiation on the tumour cells is higher compared to the high-energy X-rays or gamma rays delivered by the conventional linear accelerators based radiotherapy instruments. In the last 20 years, after its innovation, the method has been used in 38 countries, across 260 medical health centres helping 45,000 patients. The study was conducted to find the relative effectiveness of this new radiotherapy and the conventional one.

The study

Only if the ductal carcinoma is less than 3.5 cm, breast-conserving surgery is feasible. 2228 patients less than 45 years old were identified for the study. Of them, 1140 were given TARGET-IORT after the surgery, and for the remaining 1158, the conventional EBRT radiotherapy was given. The investigation began with the recruitment of first patience in March 2000 and was completed in June 2012. The patients were randomly assigned to each of these two arms of the study. After the completion in 2012, for five years, the patients were followed up. The results were encouraging. The TARGET-IORT was as effective as the older therapy, with less side effect and must less pain and hassle to the patient.

Co-author, Professor Michael Baum (UCL Surgery & Interventional Science), said: “These results are the highest level of evidence proving not only the effectiveness of TARGIT-IORT but confirming that it avoids deaths from other causes. I am pleased that it will benefit thousands of breast cancer patients around the world.”

After five year follow-up, 2.1% (24/1140 patients) who undergone TARGIT-IORT had a recurrence of localised breast cancer. At the same time, it was 0.95% (11/1158 patients) for EBRT. The difference (1.16%) in recurrence risk is minimal and clinically insignificant, concluding that TARGIT-IORT is non-inferior to EBRT. There were 14 fewer deaths (42/1140 v 56/1158) for TARGIT-IORT compared with EBRT. Further, eight out of every ten patients who had TARGIT-IORT therapy did not require post-operative radiotherapy treatments. Due to fewer radiation-related side effects compared with conventional whole breast radiotherapy, fewer women died from causes other than breast cancer from TARGIT-IORT.

Fewer side effects

The researchers also analysed the long-term follow up of patients, average 8.6 years, in some cases as long as 18.9 years. The long term analysis showed no statistically significant difference in any of the breast cancer outcomes of TARGIT-IORT treatment. Further, there was a substantial reduction in deaths from causes other than breast, indicating possible lesser side effect of radiotherapy. Besides, TARGIT-IORT was less painful, better cosmetic outcome and a better quality of life.

Co-author, Professor Jeffrey S Tobias (Professor of Clinical Oncology, UCL & UCLH) said: “They avoid side effects of whole breast radiotherapy. Importantly, TARGIT-IORT reduces the burden on overstretched radiotherapy departments.”

Commenting on the paper Dr Kanika Sood, Clinical Lead & Senior Consultant, Radiation Oncology, Dharamshila Narayana Superspeciality Hospital, New Delhi says that the long term trial conducted “has proved that TARGIT-IORT therapy in as effective as external radiation for the treatment of breast carcinoma in terms of survival. It offers the advantage of shortening the treatment time and reduces the toxicity to the underlying organs.” She further adds that the applicability is limited  “only the patients who are candidates for partial breast radiation can be offered this modality.” The usefulness of this game-changer technology in India, she points is limited as we do not have adequate screening programs, that can identify patients at an early stage. She says in India “most patients come in advanced stage who cannot be offered this treatment.”