Symposium on Cancer - September 2010
Tex Med. 2010;106(9):64-66.
By Stephen Brown, MD
Radiation therapy continues to evolve with modern computers and digital imaging. The term "adaptive" in this field addresses the desire to improve in the implementation of radiotherapy with the goal to achieve real-time imaging and planning of the target through a prescribed course of therapy. The continued evolution of radiation technology is adaptive. Technological developments in radiotherapy reduce the morbidity and toxicity of treatment, facilitate patient convenience, and improve outcome of therapy.
Modern radiation delivery systems are digital, with analog units continually being replaced with modern digital technology. The planning and delivery of radiation therapy are computer-controlled events with electronic digital image acquisition and verification at the time of therapy. A majority of radiation therapy treatment planning now incorporates three-dimensional anatomy attained by computed tomography (CT) images for registration. These images can be fused with magnetic resonance imaging (MRI) or positron emission tomography (PET) images for further definition of the target volume.
Radiation has always been delivered with image guidance. The evolution has been from plain film, two-dimensional, bone-based anatomy x-ray anteroposterior and lateral fields, to three-dimensional, oblique conformal fields, employing open fields. The foundation for accurate planning relies on volume-based imaging. This static image acquisition at one point in time allows for adequate localization of the treatment target. All of these progressions of technology have maximized the ability to focus radiation on the static target. Further development of radiation delivery will be the advancement of adaptive technology to address the motion of the target and account for treatment effect or the actual change in the target.
The key individuals responsible for the rapid development of radiation technology are the physicists involved in the field of radiation oncology and diagnostic imaging. The physician and the physicist remain the most integral parts of these radiation delivery systems. The support staff for a radiation oncologist includes the physicist, dosimetrist, radiation therapy technologist, and oncologic nurses. Responsibility for quality assurance and maintenance of the equipment, development, and implementation of a treatment plan, as well as delivery of therapeutic radiation to every patient, remain the goals of this team. Without these fundamental components of delivery, the quality assurance to provide precision and accuracy of radiotherapy cannot be maintained.
Radiation can comprise photons or packets of energy called x-rays or gamma rays or can exist as particles of energy with mass. The particulate form of radiation includes electrons, protons, and neutrons. Ionizing radiation forms ions in the cells of tissues it passes through, dislodging electrons from atoms. This ionization event can kill cells or change the genetic structure of the genes in the nucleus of the cell. This event is described as a direct hit or indirect hit on the genetic code. Indirect hits result in free radical formation generating hydroxyl-free radicals that can result in multiple events impacting the genetic code. Without functioning DNA, the cancer cells can no longer function properly or repair, leading to apoptosis or "programmed cell death." Cancer cells have lost the ability to repair genetic damage. When cell division occurs, these cancers cells cannot duplicate their genetic code. Without this capacity, apoptosis occurs, and the cancer cells destroy themselves. This is the biologic event of radiation therapy. This event in radiation defines the ability of radiation to selectively affect cancer cells while minimizing damage to normal tissue. The ability of the normal tissue to repair to the damaged tissue allows for organ preservation.
The amount of radiation and duration of treatment depend on the radiosensitivity of the cancer target and the sensitivity of the surrounding organs. A delicate balance must be maintained among the daily dose, total dose, and curative intent. A radiation oncologist delivers a dose to a target to optimize the tumor cell kill, while minimizing the effects to normal tissues surrounding the target organ. The surrounding normal tissues are referred to organs at risk. The impact or radiation dose on normal tissues may lead to short-term and long-term side effects from the inability to repair the radiation damage. Each organ in the human body has a sensitivity or threshold dose for the amount of radiation dose tolerance. The radiation oncologist prescribes a course of therapy, recognizing the risk-to-benefit ratio of the delivered therapeutic dose of radiation. The decision between multiple treatments, referred to as fractionation, or single treatments known as ablative therapy, will be determined on the basis of therapeutic outcome.
Doses of radiation can be delivered in large, single treatments, hypo-fractionation, or fractions of multiple treatments. The single, large dose of radiation is referred to as an ablative dose. This dose will not allow for the repair of target tissue. High-dose-rate (HDR) brachytherapy systems and stereotactic radiosurgery systems employ these large ablative doses to deliver precise, localized treatment. Low-dose-rate (LDR) brachytherapy systems and standard linear accelerator dose schedules deliver lower doses of radiation over a prolonged period of time. Multiple treatments or fractions of radiation consisting of a lower daily dose are delivered over a period of weeks to months. These lower dose-rate schedules, referred to as therapeutic doses of radiation, allow normal tissue to repair.
Two basic types of radiation delivery systems exist: brachytherapy (short-distance) systems and teletherapy (long-distance) or external beam radiotherapy systems. These systems deliver high doses of radiation to precisely localized targets.
Brachytherapy systems implant radioactive material directly into tissue physically or by placing a silastic hollow catheter into and through the involved tissue or organ.
Brachytherapy's ability to concentrate high doses of radiation in target tissue without effecting surrounding tissues has merited benefit. The silastic catheters once implanted are then later loaded with radioactive sources. The catheter placement, geometry, and tumor coverage have to be confirmed and validated by imaging.
Brachytherapy systems can employ LDR sources or HDR sources. The trend has been a gradual evolution toward HDR-based systems to reduce the duration of treatment, to provide patient convenience, and to reduce staff radiation exposure and increase overall safety. LDR brachytherapy implants traditionally have required overnight hospitalizations. The carrier device, consisting of soft pliable catheters or rigid stainless steel applicators, would be placed and positioned in the patient in the operating room under general anesthesia.
After the position of the carrier device location was confirmed by imaging, the radioactive sources were loaded into the device for a 2- to 3-day period. The patient was isolated in a lead-lined, in-patient hospital room. Radiation precautions were posted, with time limits to visitors and hospital staff during the hospitalization.
Today, modern brachytherapy applicators are synthetic sleeves or catheters that can be sewn into place. The three-dimensional placement of the after-loading device is validated by CT imaging. Once the position is approved, actual dosimetry for delivery of the radiation dose can be planned and tailored to the patient's anatomy and disease site. Outpatient treatment can be performed daily or twice daily, lasting 20 to 30 minutes.
The patient may leave and travel with the implantable sleeve or catheter to return for therapy on the following schedule. Treatment occurs during an outpatient office visit. The after-loading carrier device is coupled to a catheter affixed to the HDR radioactive source train supply device. This system has the radioactive source train attached to a thin, long wire that is computer controlled to deploy the source a predetermined length and time, referred to as dwell time. A prescribed dose of radiation is delivered to the target tissue by a radioactive source inside the catheter. This will be removed from the catheter by the source train wire and retracted into a sealed storage container. Therapy for all patients is monitored outside of the radiation vault. The patient may leave with the after-loading device securely in place. This allows for patient convenience and ability to maintain daily activities and to schedule the next treatment at a specified time.
HDR devices are now employed routinely to deliver partial breast brachytherapy. A woman diagnosed with breast cancer may choose between 6 weeks of daily external beam therapy or 5 days of partial breast HDR therapy. HDR applicators also exist to treat skin cancer, cervical and endometrial cancer, and soft-tissue sarcomas.
The delivery of radiation therapy within facilities by equipment continues to be modernized. The delivery systems vary by manufacturers, with each vendor offering proprietary hardware and software. A linear accelerator (LINAC) produces a beam of photons or charged particles, which is the radiation beam. The beam can be modified to conform to the target outline. Diagnostic imaging will delineate the target outline.
Radiotherapy targets included the tumor volume and first- and second-order draining lymphatics. Treatments were first prescribed as coplanar parallel opposed beams with rectangular appearing fields. With CT imaging, the anatomic target definitions encompassed organ volumes and margins of normal tissue. This would allow the patient to be set up for treatment with a certain degree of uncertainty, while still acquiring the target in the proposed treatment fields. These parameters are typical when defining static volumes. Treatment fields are based on a static image acquisition at one point in time. That reference image or planning images are then employed during the entire course of therapy.
Multiple coplanar beams were first deployed around a treatment target in a pinwheel fashion and labeled as three-dimensional conformal treatment planning and therapy. The target defines the shape of each of these treatment fields. The designed custom shape or pattern was fabricated into cerrobend blocks to protect the normal tissues and organs around the target from the radiation beam. Field shaping and blocking have evolved with modern technology and computers with the development of multileaf collimators (MLCs). These computer-controlled leaves or blocks move in and out of the beam to modulate the intensity of the beam and protect the normal tissue by blocking the beam. Intensity-modulated radiation (IMRT) allows the dose of radiation to be conformed or shaped more precisely to the target, while sparing normal tissue around the target. IMRT has been deployed on a static planning target volume in a step-and-shoot fashion.
Radiation oncologists now account for target and organ movement associated with bodily function such as respiration. The greatest problem encountered when employing CT data acquisition remains the distortion of the target image. Four-dimensional CT scans employ the three-dimensional target anatomy collected with multiple CT scans at various points in the respiratory cycle called gating. CT is performed at inspiration, expiration, and resting breathing phases. These images are fused, and the target volumes are contoured from all images and phases of respiration to account for organ movement creating an internal target volume.
As sophisticated as these techniques appear, simple fluoroscopy provides as reliable assessment of target movement during the respiratory phase. The treatment is deployed in standard IMRT point-and-shoot fashion. Treatment delivery continues to evolve from static point-and-shoot techniques to dynamic delivery of radiation. The radiation beam remains on as the machine rotates around the patient without stopping. This effectively reduces treatment time to deliver the prescribed dose of radiation.
LINAC systems attached to CT imaging units, or rotated in image acquisition around a patient, can provide dynamic therapy and imaging simultaneously. LINAC systems attached to robots allow all six axes of movement and incorporate paired orthogonal fluoroscopy imaging for real-time tracking of targets. The goal of these delivery systems is to precisely localize the target and accommodate for organ movement within the patient.
Stereotactic Body Radiosurgery
With the advent of improved radiation delivery systems has been the development of digital imaging localized treatment targets. Electronic portal imaging devices mounted to the LINAC provide localization of static reference points in two-dimensional and three-dimensional references. LINAC systems incorporate fluoroscopic orthogonal real time imaging to localize targets at the time therapy is being performed. The advent of real-time image acquisition at the time of treatment constitutes the most active tracking of the target and organ motion during therapy. The incorporation of this information into the treatment plan and adjusting for treatment effect on the target defines adaptive radiotherapy. With the advent of more precise tracking and targeting of treatment volumes, stereotactic body radiosurgery (SBRT) has evolved. The ability to deliver high doses of radiation in small numbers of fractions or treatments and have equivalent or better outcomes than standardized therapy is of age. The implementation of an SBRT program requires robust physics, engineering, and computer technology support to provide the quality assessment and assurance in these programs. Delivering SBRT occurs with very sophisticated high-tech instruments requiring cutting-edge technology. These systems provide the most accurate delivery of therapeutic radiation.
With these modern, advanced radiotherapy tools, radiation oncologists continue to expand the capabilities and delivery of medical radiation therapy. Adaptive radiotherapy requires these types of systems to be in place. With adaptive radiotherapy, the next level of optimization and therapeutic efficacy occurs. Replanning the delivery of radiation dose when significant volumetric change in the size of the target occurs during a treatment course allows effective dose delivery adjusted to accommodate for the biologic effect and change on the target. The result is to reduce further toxicity to the patient and increase therapeutic outcome. The frontier of adaptive therapy has arrived and will be applied to all aspects of radiation oncology.
Stephen Brown, MD, is a radiation oncologist in Austin.
September 2010 Texas Medicine Contents
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