Intraoperative radiation therapy

Intraoperative radiation therapy is applying therapeutic levels of radiation to a target area, such as a cancer tumor, while the area is exposed during surgery.

Applications

The goal of IORT is to improve local tumor control and survival rates for patients with different types of cancer. Targeted intraoperative radiotherapy is a technique developed since 1998 for treatment of the tumour bed after wide local excision (lumpectomy) of breast cancer. The 5-year results of the TARGIT-A trial, which recruited 3451 patients, were presented at 2012 San Antonio Breast Cancer Conference and show that giving TARGIT at the time of lumpectomy in ER+ PR+ patients, aged 45 years and over, gives results similar to whole breast radiotherapy in terms of local cancer control, with fewer non-breast cancer deaths and a trend for lower overall mortality. 2012 SABCS, Thursday 6 December, General Session 4. These 5-year results equivalent to several weeks of whole breast radiation therapy, were published in the Lancet Full pdf text

Rationale

The rationale for IORT is to deliver a high dose of radiation precisely to the targeted area with minimal exposure of surrounding tissues which are displaced or shielded during the IORT. Conventional radiation techniques such as external beam radiotherapy (EBRT) following surgical removal of the tumor have several drawbacks: The tumor bed where the highest dose should be applied is frequently missed due to the complex localization of the wound cavity even when modern radiotherapy planning is used. Additionally, the usual delay between the surgical removal of the tumor and EBRT may allow a repopulation of the tumor cells. These potentially harmful effects can be avoided by delivering the radiation more precisely to the targeted tissues leading to immediate sterilization of residual tumor cells. Another aspect is that wound fluid has a stimulating effect on tumor cells. IORT was found to inhibit the stimulating effects of wound fluid.^[1]

Methods

IORT can both be performed with electron beams (IOERT) and X-rays. Modern IORT started in shielded operation rooms in which a linear accelerator was used to deliver the radiation. In recent years, miniaturised and mobile-linear accelerators have been developed which deliver a variable range of electron energies (from 3 to 12 MeV), e.g. the Mobetron (Intraop Medical Corporation, USA). Intrabeam, (Carl Zeiss, Germany) is a miniature and mobile X-ray source which emits low energy X-ray radiation (max. 50 kV) in isotropic distribution. Due to the higher ionization density caused by soft X-ray radiation in the tissue, the relative biological effectiveness (RBE) of low-energy X-rays on tumor cells is higher when compared to high-energy X-rays or gamma rays which are delivered by linear accelerators. The radiation which is produced by mobile radiation systems has a limited range. For this reason, conventional walls are regarded sufficient to stop the radiation scatter produced in the operating room and no extra measures for radiation protection are necessary. This makes IORT accessible for more hospitals.

Clinical Applications

IORT was found to be useful and feasible in the multidisciplinary management of many solid tumors but further studies are needed to determine the benefit more precisely. Single-institution experiences have suggested a role of IORT e.g. in brain tumors and cerebral metastases, locally advanced and recurrent rectal cancer, skin cancer, retroperitoneal sarcoma, pancreatic cancer and selected gynaecologic and genitourinary malignancies. For local recurrences, irradiation with IORT is besides brachytherapy the only radiotherapeutic option if repeated EBRT is no longer possible. Generally, the normal tissue tolerance does not allow a second full-dose course of EBRT, even after years.

IORT in Breast Cancer

The largest experience with IORT and the best evidence for its potentials exists in breast cancer where a substantial number of patients have already been treated using, for example, the TARGIT (TARGeted Intraoperative radioTherapy) technique which gives 20 Gy to the surface of the applicator balloon and 5-7Gy 1 centimeter away.

On 11 November 2013 the 5-year results of local recurrence and overall survival from the TARGIT-A trial of TARGIT IORT for breast cancer were published in the Lancet.^[2] (full TARGIT IORT paper). 3451 patients from 33 centres in 11 countries participated in the trial. The analysis of the data found that

• with longer follow up, the results are stable,
• local recurrence in the conserved breast with TARGIT concurrent with lumpectomy is similar to whole breast radiotherapy,
• breast cancer mortality is similar with TARGIT and EBRT, and
• deaths from causes other than breast cancer- cardiovascular and other cancers - are significantly reduced.

The conclusion was that TARGIT concurrent with lumpectomy within a risk-adapted approach should be considered as an option for eligible patients with breast cancer carefully selected as per the TARGIT-A trial protocol, as an alternative to postoperative EBRT. The results of TARGIT TARGIT IORT for breast cancer are discussed in a podcast of the TARGIT-A and ELIOT trials on the Lancet website.. As the effect of radiotherapy on local recurrence of breast cancer is mostly in the first 2–3 years and almost none after the first 5 years, it is thought that sufficiently large number of patients in the TARGIT-A trial have an adequately long follow up . A robust response to scientifically weak criticisms for use of TARGIT IORT during lumpectomy breast cancer, including a decision aid (figure 4) is given in the Red Journal.^[3] On 25 July the UK National Institute for Health and Care Excellence (NICE) gave provisional recommendation for the use of TARGIT IORT with Intrabeam in the UK National Health Service.^[4] The 2015 update of guidelines of the Association of Gynecological Oncology (AGO), an autonomous community of the German Society of Gynecology and Obstetrics (DGGG) and the German Cancer Society includes TARGIT IORT during lumpectomy as a recommended option for women with a T1, Grade 1 or 2, ER positive breast cancer -see 2015E_Updated_guidelines_p633

See also

• Intraoperative Electron Radiation Therapy (IOERT) IOERT
• Brachytherapy Brachytherapy
• External beam radiotherapy (EBRT) EBRT

References

• Intraoperative radiation therapy at Cancer Treatment Centers of America
• Internal radiation therapy, cancer.org
• Interoperative radiation therapy at Mayo Clinic
• Cancer therapy offers one-time radiation dose
• a mobile electron linear accelerator for IORT
• Report of AAPM Radiation Therapy IORT Committee Task Group No. 72
• IORT for breast cancer with TARGIT

References