UroToday - Current Status of Intensity-Modulated Radiation Therapy (IMRT)

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Thursday, 21 February 2008

BERKELEY, CA (UroToday.com) - In the International Journal of Clinical

Oncology, Dr. Hatano and colleagues from Chiba, Japan provide an excellent

overview of intensity-modulated radiation therapy (IMRT). Problems with

conventional, four field radiotherapy have been ineffective dose

distribution and overdoses to organs at risk (OARs), such as the bladder and

rectum. The use of dose escalation from 64Gy to 81Gy improves tumor response

but increases toxicity. Three-dimensional conformal radiotherapy (3D-CRT) is

a technique to increase dose while conforming the beam to the target organ

but still has toxicity limitations. IMRT has been introduced for dose

escalation with the goal of minimizing toxicity to the bladder and rectum.

In fact, IMRT is an advanced form of 3D-CRT where there is enhanced control

over the 3D-CRT dose distribution through the superposition of a large

number of independent segmented fields either from a number of fixed

directions or from directions distributed on one or multiple arcs. IMRT

therefore, requires dose specifications for both the target and the

surrounding normal structures.

IMRT planning includes the target, OAR contouring, and the dose

prescription. A CT simulator is used to contour the prostate, seminal

vesicles, and normal structures in order to generate high-resolution 3D

reconstructions. Patients receive treatments in a thermoplastic cast for

daily reproducibility of positioning. Treatments can be in the supine or

prone position but studies suggest that for prostate cancer (CaP) treatment

the internal organ motion is less in the supine position. Between

treatments, interfraction organ motion occurs, and one study showed

displacements of 1.2mm, 0.5mm, and 0.6mm in the anterior-posterior,

superior-inferior, and lateral directions, respectively. To minimize

interfraction organ motion, implantation of radio-opaque seeds in the

prostate, and tracking of the daily position using orthogonal x-rays, or

portal imaging devices are often employed. Some have advocated the use of a

rectal balloon for rectal distension to minimize rectal toxicity, but the

authors summarize that there is no consistent view of the role of the rectal

balloon. Newer techniques include electromagnetic treatment target

positioning and continuous monitoring systems.

In IMRT the clinical target volume (CTV) delineation is critical. The CTV

may include only the prostate in low-risk patients but incorporate 1 or 2cm

of the seminal vesicle in intermediate or high-risk patients. Risk

evaluation includes the number and location of positive prostate biopsies

and risk assessment, such as the " Partin tables " . Inclusion of the pelvic

lymph nodes is controversial but IMRT potentially allows for lower toxicity

to the pelvic nodes. The external walls of the rectum and bladder and

femoral heads and penile bulb are also delineated.

The treatment plan for IMRT employs multiple fields each with a relative

weighting, which may be delivered with a device that modifies the beam

intensity within the field itself. There is a tradeoff between the target

coverage, avoidance of critical structures, and the inhomogeneous coverage

of the target volume and small dose to the adjacent OARs. Numerous authors

have reported the risk of rectal and bladder complications as a continuous

function of dose. For example, the dose constraints for the rectum limit the

volume for 65Gy or more to 17%or less and for 40Gy or more to 35% or less.

Dose escalation has been shown to be of benefit in patients with adverse

features using both conventional and 3D-CRT. However, the toxicities also

increase with increasing dose. In a recent study using IMRT the 8-year

actuarial PSA relapse-free survival rates for patients in favorable,

intermediate, and unfoavorable risk groups by the ASTRO criteria were 85%,

76%, and 72%, respectively. The likelihood of grade 2 rectal toxicity was

1.6%. Hypofractionated IMRT has also been studied. A report by Pollock

compared 76Gy in 38 fractions to 70.2Gy in 26 fractions. There was no

difference in overall maximum acute GI or GU toxicity but a slight increase

in the 70.2Gy arm GI toxicity was seen during weeks 2-4.

Problems with IMRT include that a larger volume of normal tissue being

exposed to lower doses of radiation compared to conventional techniques.

This will have the effect of increasing the risk of a fatal secondary

malignancy. One report suggests an increase of 1.5% in elderly patients by

10 years after treatment. Shielding in the treatment head, secondary beam

blocking, and a not using a flattening filter are potential ways to decrease

the problem of leakage radiation.

In summary, IMRT may enhance the therapeutic ratio by minimizing morbidity

and may permit the treatment of larger volumes such as the whole pelvic

nodal region with a higher curative dose, while maintaining acceptable

morbidity.

Hatano K, Araki H, Sakai M, Kodama T, Tohyama N, Kawachi T, Imazeki M,

Shimizu T, Iwase T, Shinozuka M, Ishigaki H

Int J Clin Oncol. 12(6):408-15, December 2007

doi:10.1007/s10-9

PubMed Abstract

PMID:18071859