RADIATION THERAPY ONCOLOGY GROUP   RTOG 0438
A PHASE I TRIAL OF HIGHLY CONFORMAL RADIATION THERAPY FOR PATIENTS WITH LIVER METASTASES

The liver tolerance to external beam irradiation depends on the volume treated and the fractionation schedule. Lawrence, et al found that patients who developed grade III or IV radiation induced liver disease (RILD) tended to receive a higher mean dose and have less sparing of normal liver than those who did not.

In the original analysis, none of the 45 patients who received a mean dose to the whole liver of less than 37 Gy (in 1.5 Gy per fraction bid) developed RILD, while 9 of 34 patients who received a mean dose of more than 37 Gy developed this complication. Another study from the University of Michigan looked at 26 patients with hepatobiliary cancer treated with radiation doses up to 72.6 Gy, in 1.5 Gy bid and concurrent intrahepatic fluorodeoxyuridine administration. Patients treated with a component of 36 Gy whole liver radiation were more likely to develop RILD compared to those treated with focal high-dose radiation with no whole liver radiation. These studies indicate that by using modern conformal radiation planning it is possible to deliver tumoricidal doses of radiation. More recently, we have developed a better understanding of the relationship between dose, volume of liver irradiated and RILD, based on an analysis of over 200 patients with hepatic malignancies treated

RADIATION THERAPY:

Note: Intensity Modulated RT (IMRT) Is Not Allowed. H2 blockers or proton pump inhibitors will be required in an attempt to decrease the chance of late GI bleeding.

Radiation Therapy must start within 4 weeks of patient registration. (1/10/06)

Dose Specification

The target dose is determined based on the study dose level and the volume of normal liver excluded from radiation (using the liver DVH) see Section 6.5. Treatment at the allocated dose level is only permitted if the normal tissue criteria in Section 6.5 are maintained. If the normal tissue criteria are not met at that dose, treatment at a lower dose level is permitted, as long as the normal tissue constraints are met at the lower dose level.

The dose per fraction to the PTV will start at dose level II (4.0 Gy), but may vary from 3.5 Gy to 5.0 Gy, in 10 fractions, Monday through Friday, in 0.5 Gy increments, as described in Section 13.0. The starting level will be Level II, 4.0 Gy per fraction.

Doses will be prescribed to a peripheral covering isodose covering the PTV. Assuming dose is normalized to this isodose at 100%, the maximal dose can be 120% and the minimum PTV dose 90%. Any dose > 110% must be within the PTV. Minor variation is defined as minimum PTV dose falling between 85 and 90% (of the required 100% isodose prescription). Major variation (unacceptable) is defined as minimum PTV dose < 85 % (for the required 100% isodose prescription).

Treatment Planning/Volume Definitions

CT-based 3D treatment planning shall be used for all patients.

The gross tumor volume (GTV) will be defined by IV contrast CT or MRI. If defined on MRI, the study must be obtained using the same breath hold technique as the planning CT, and registered to the planning CT dataset.

The clinical target volume (CTV) will be the GTV + 5 mm, within the liver.

The planning target volume (PTV) will be determined by the immobilization device used and/or the individual patient breathing motion. The minimal and maximal PTV margins permitted are 4 mm and 10 mm, respectively.

Critical Structures

Normal Liver: The normal liver is defined as that portion of liver not radiographically involved by gross tumor (Normal liver volume minus GTV). In all patients, it is required that there is at least 1000 cc of normal liver. No more than 30% of the normal liver may receive more than 27 Gy, and no more than 50% of normal liver may receive over 24 Gy.

Kidney: For patients with only one functioning kidney or creatinine > 2.0 mg/dl, no more than 10% of the functioning kidney(s) may receive 10 Gy or more. For patients with normal creatinine and two functioning kidneys, no more than 33% of the combined renal volume may receive 18 Gy or more.

Spinal Cord: Maximal permitted dose to spinal cord is 34 Gy.

Small Bowel: Maximal permitted dose to small bowel is 37 Gy for any 1cc volume.

Stomach: Maximal permitted dose to stomach is 37 Gy for any 1cc of volume.

All doses are physical doses (not biologically corrected). Note that 37 Gy is biologically equivalent to 50 Gy in 2Gy/fraction using an α/β of 3.