Know it, to control it

Fractionation in Liver and Kidney Cancers

Stereotactic body radiation therapy (SBRT) or Stereotactic Body Arc Therapy(SABR) and Single dose Radiotherapy(SDRT) are ablative irradiation modalities.The exposures of radiation here are  delivered in a single or  less than 5 fractions aided by image-guided radiation therapy. Liver SBRT aims to treat hepatic metastasis in a curative intent as surgery and primary liver tumors also benefit from SBRT either exclusively or as a bridge to transplantation.

SBRT provides a very high doses per fraction, delivered daily or every second day. The number of fractions varies, with 3–5 fractions being used commonly. The dose delivered is the most important factor affecting local control along with tumor volume, and the tumor being primary or metastasis. Besides killing the cancer cells in all phases of cell cycle(including the resting phase G0), there is sudden breakdown of the surrounding connective tissue (holding the cancer cells together) and a shutdown of the direct and indirect blood supply through the blood vessels that are disrupted due to the high dose of radiation.The cancer tissue has a fragile and weak blood supply system that is not as robust as that of the body’s normal system and cannot repair itself without the normal blood supply.

However exposing the body to 3 to 6 high dose fractions is challenging or impossible when the tumors are large (>10cms)and near critical organs at risk such as the spinal cord and the gastrointestinal tract. Delivering biologically equivalent doses of up to 140 Gy (Biologically equivalent dose) to the hypoxic core of the tumor has been found to be safe and may lead to improved tumor control.

Renal cancers are considered as radio resistant cancers, and radiotherapy was earlier considered  a palliative modality . However, a few (even single) fractions of ablative SBRT,at a high fraction dose are used in primary and in oligo metastatic disease.

There is an established biological rationale for the radio sensitivity of renal-cell carcinoma (RCC) to SBRT, which is activated only when a high dose per fraction is given. Apart from the direct effect of SBRT, an abscopal effect can also be induced caused by immunological processes .

The breakdown of the cancer cells releases antigens (that the body can identify as harmful or foreign particles) that can sensitize the body’s own immunity in identifying the cancer as a harmful agent. This leads to the breakdown products act as a vaccine activating the body’s defence mechanisms and start destroying this invader from within.

A single dose of RT (15 Gy–20 Gy) induces the activation of body’s immune mechanism thereby rendering the liver and renal metastases and primary tumours amenable to being destroyed within the body.