Lecture 22 Radiobiological aspects of alternative dose delivery system

Lecture 22Lecture 22 Ahmed GroupAhmed Group

Lecture 22

Radiobiological aspects of alternative dose delivery system


ProtonsHigh LET sourcesBNCTStereotactic radiosurgery/radiotherapy,IMRT, IORT: Dose distribution and dose heterogeneity


Alternative Radiation Modalities

The early recognition that X-rays could produce local tumor controlin some patients and not in others led to the notion that other formsof ionizing radiations might be superior.

In the case of neutrons, they give up their energy to producerecoil protons, alpha-particles, and heavier nuclear fragments.Consequently, their biologic properties differ from those of X-rays: reduced OER, little or no repair of sublethal damage, and lessvariation of sensitivity through the cell cycle.Protons have radiobiologic properties similar to those of X-rays;Negative π-mesons and heavy ions were introduced with the hopeof combining the radiobiologic advantages attributed to neutronswith the dose distribution advantage characteristic of protons.



Neutrons - superior to X-rays in a limited number of situations,specifically for prostate cancer, salivary gland tumors, andpossibly soft-tissue sarcomas;Protons - used for treatment of uveal melanoma and tumors suchas chordomas-they are located close to spinal cord and benefit fromthe localized dose distribution. The wider use of protons for broad-beam radiotherapy is being tested now.Negative π-mesons and heavy ions have been used to treat hundredsof patients, but the trials have never been completed to prove theirsuperiority over conventional X-rays.


Fast NeutronsThe first clinical use of neutrons


Fast Neutrons. Practical sources


The only practical sourceof neutrons for clinicalradiotherapy is a cyclotron.Cyclotron is an electricdevice capable of acceleratingpositively charged particles,such as protons or deuterons,to an energy of millions ofvolts



Fast Neutrons

More recently, cyclotrons toproduce neutrons have beenbuilt using the p+ Be reaction.The cyclotron can be smallenough to be installed in a hospital.Neutron spectra produced by thetwo processes are shown


Percentage Depth Doses for Neutron Beams

An essential factor in the choice of a neutron beam for clinical useis its ability to penetrate to a sufficient depth.


Current Efforts with Neutrons

Emphasis is being placed on two factors:

• First, subgroups of patients with specific types of tumors that may benefit from neutrons must be found.

• Second, different fractionation patterns will be tried for neutrons.


Current efforts with neutronsEmphasis will be placed on slowly growing tumors, in view ofthe observation of Breuer and Batterman that neutron RBE,measured from pulmonary metastases in patients, increasesas tumor volume doubling time increases


Protons

Protons are attractive for radiotherapy because of their physicaldose distribution. The RBE of protons is undistinguishable fromthat of 250-kV X-rays, which means that they are 10 to 15% moreeffective than cobalt-60 gamma-rays or megavoltage X-raysgenerated by a linear accelerator.The OER for protons is undistinguishable from that for X-rays,namely about 2.5 to 3.These biologic properties are consistent with the physicalcharacteristics of high-energy proton beams; they aresparsely ionizing.


Protons

The dose deposited by a beam of monoenergetic protons increases slowly with depth, but reaches a sharp maximum near theend of the particle’s rangein the Bragg peak.Proton beams ranging in energy from 150 to 200 MeV are of interest in radiotherapy because this corresponds to a range in tissue of 16 to 26 cm.


Protons

The way theBragg peak canbe spread out toencompass a tumorof realistic size isshown.The spread-outBragg peak can bemade narrower orbroader asnecessary


ProtonsMany researchers consider protons to be the treatment of choice forchoroidal melanoma.Protons have found a small but important place in the treatment ofocular tumors and also some specialized tumors close to the spinal cord


Protons

Current proton therapy facilities worldwide, light- and heavy-charged-particle facilities, and the number of patients treated


Protons


ProtonsMost of the protons machines were built initially for physicsresearch and were located in physics laboratories.


ProtonsHigh LET sourcesBNCTStereotactic radiosurgery/radiotherapy,IMRT, IORT: Dose distribution and dose heterogeneity


Boron Neutron-Capture Therapy (BNCT)

The basic idea behind boron neutron-capture therapy (BNCT) iselegant in its simplicity.The idea is to deliver to the cancer patient a boron-containingdrug that is taken up only in tumor cells and then to expose thepatient to a beam of low-energy (thermal) neutrons that themselvesproduce little radiobiologic effect but that interact with the boronto produce short-range, densely ionizing alpha-particles.Thus, the tumor is intensely irradiated, but the normal tissuesare spared.



There are two problems inherent in this idea:

1. What is a “magic” drug that distinguish malignant cells from normal cells?

2. The low-energy neutrons necessary for BNCT are poorly penetrating in tissue



Boron compounds

For BNCT to be successful, the compounds used should havehigh specificity for malignant cells, with low concentrationsin adjacent normal tissues and in blood.

The two classes of compounds have been proposed:1. Low-molecular weight agents that simulate chemical precursorsrequired for tumor cell proliferation, can traverse cell membraneand be retained intracellularly.Two boron compounds, theBSH and BPA, have been identified and used to treat brain tumors.



Boron compounds

2. High molecular-weight agents such as monoclonalantibodies and bispecific antibodies. These are highly specofoc, but very small amounts reach brain tumors following systemic administration.Boron-containing conjugates of epidermal growth factor, thereceptor for which is overexpressed on some tumors,also have been developed.


Neutron Sources for BNCT

During fission within the core of a nuclear reactor, neutronsare “born” that have a wide range of energies. Neutron beams can be extracted from the reactor.Current interest in the United States focuses on the use ofepithermal neutron beams (1-10,000 eV), which have a greaterthan thermal neutrons (0.025 eV) depth of penetration.These neutrons do not themselves interact with the boronbut are degraded to become thermal neutrons in the tissueby collisions with hydrogen atoms.The need for a nuclear reactor as a source for neutrons is a serious limitation and would preclude BNCT facilitiesin densely populated urban areas.


• Protons• High LET sources• BNCT• Stereotactic radiosurgery/radiotherapy,• IMRT, IORT: Dose distribution and dose

heterogeneity


Stereotactic radiosurgery/radiotherapy


What is stereotactic radiosurgery? Stereotactic radiosurgery is a medical procedure that utilizes very accurately targeted, large “killing”doses of radiation. This noninvasive “operation”has proven to be an effective alternative to surgery or conventional radiation for treating many small tumors and a few other select medical disorders. Standard stereotactic techniques rely on a rigid metal frame fixed to apatient’s skull for head immobilization and target localization. However, such frame-based systems have numerous limitations,including: 1) restricting treatment to the brain, 2) limiting the possible angles which radiation could be delivered,3) causing considerable discomfort for the patient. In contrast to the standard frame-based radiosurgical instruments, the CyberKnife uses noninvasive image-guided localization, and a robotic delivery system. This combination of technologies enablesthe CyberKnife to overcome the limitations of older frame-based radiosurgery such as the Gamma Knife and LINAC.



What is image-guided CyberKnife radiosurgery? The present design of the CyberKnife derives from the original concept of a frameless alternative to frame-based radiosurgery. The CyberKnife consists of three key components: 1) an advanced, lightweight linear accelerator (LINAC) (this deviceis used to produce a high energy (6MV) "killing beam" of radiation),2) a robot which can point the linear accelerator from a wide varietyof angles, and 3) several x-ray cameras (imaging devices) that are combined with powerful software to track patient position. The cameras obtain frequent pictures of the patient during treatment, and use this information to target the radiation beam emitted by the linear accelerator. The robot is instrumental in precisely aiming this device. When a patient moves during treatment, the change in positionis detected by the cameras, and the robot compensates by re-targeting the linear accelerator before administering the radiation beam.



This process of continually checking and correcting ensures accurate radiation targeting throughout treatment.In summary, the CyberKnife replaces the stereotactic head frame with a patient-friendly image-guided localization system. This technology has the added benefit of enabling the CyberKnife to be used for radiosurgical applications outside the brain and for staged radiosurgery. It is difficult if notimpossible to perform these other procedures with standard frame-based radiosurgical systems

Stereotactic radio-surgery/radiotherapy


Stereotactic radio-surgery/radio-therapy

Performance characteristics for gamma knife


Stereotactic radio-surgery/radio-therapy

Test of thegamma-knife


Stereotactic Radiosurgery involves a radiation treatment procedure designed to treat small intracranial tumors. The radiation is produced by a linear accelerator that is collimated (focused) to create a small beam size and directed towards the center of the the treatment field. The tumor's location is pinpointed in the intracranial space using a stereotactic method that accesses diagnostic images (CT scans) and markers to allow a positioning frame to be mounted on the patient's head for reference when treatment is started. Radiation treatment beams are directed to the target by rotation of the therapy machine through various arcs around the patient's head.


Example. The Novalis Shaped Beam Surgery system represents cutting-edge technology for the delivery of highly precise radiation treatments within the brain as well as other areas of the body. The Novalis system will allow a multidisciplinary group of medical specialists to showcase the latest innovation in stereotactic radiosurgery. The Novalis system features an image-guided localization technique to allow radiation oncologists to pinpoint tumors with sub-millimeter accuracy and to position patients automatically and with a higher degree of precision. The Novalis system is able to precisely contour the shape of a tumor from any angle and achieves a more consistent superior dose distribution. Radiosurgery is a proven alternative for many indications in the brain, head and neck and spine. The Novalis system represents an advancement that will allow neurosurgery, surgical and radiation oncology teams a wider ranger of applications for radiosurgery throughout the body.


The Novalis system


The Novalis system


The Novalis system


IMRT

The development of Intensity Modulated radiation Therapy(IMRT), tomography, and proton/light-ion beams results ingreatly improved dose distributions, with more limiteddoses to normal tissues for comparable tumor doses. This suggests the attractive possibility of increasing the dose perfraction, since the need to spare late responding normaltissues by fractionation is reduced, because of the lowerdose to these tissues


A typical dose distribution that can be obtained with IMRT (intensity-modulated proton therapy) compared with intensity-modulated photon therapy is shown on the next slide.It is striking that with protons, the dose can be confined to thetarget volume, with much less irradiation of normal structures.With photons, a large fraction of the lungs are exposed to low doses of radiation.

Photons IMRT


Dose distribution obtained with PhotonsIMRT compared with Protons IMRT


Carbon Ion Radiotherapy

There is a sufficientrenaissance of interest in heavy-ion radiotherapy, in particular, on high-energy carbon ions.

The depth at whichthe Bragg peak occursdepends on the energyof carbon ions

Depth-Dose Profiles


Carbon Ion Radiotherapy RBE considerations

For carbon ions RBE increasestoward the end of the particlerange. The rapid change of RBEwith depth is shown

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Lecture 22 Radiobiological aspects of alternative dose delivery system