Experimental Radiology

field_vote: 

On this page, we will list all kinds of Experimental Radiological Cancer Therapies, including Radionukleid Therapies.

Therapeutic intervention: 
Disease(s): 

Carbon-ion treatment

field_vote: 

Heavy-ion therapy

From Wikipedia

Heavy-ion therapy is the use of particles more massive than protons or neutrons, such as carbon ions. Compared to protons, carbon ions have an advantage: due to the higher density of ionization at the end of their range,[8] correlated damages of the DNA structure within one cell occur more often so that it becomes more difficult for the cancerous cell to repair the damage. This increases the biological efficiency of the dose by a factor between 1.5 and 3. Compared to protons, carbon ions have the disadvantage that beyond the Bragg peak, the dose does not decrease to zero,[8] since nuclear reactions between the carbon ions and the atoms of the tissue lead to production of lighter ions which have a higher range. Therefore, some damage occurs also beyond the Bragg peak.

By the end of 2008, more than 5,000 patients had been treated using carbon ions.[5]

At the end of 2013, around 13 000 patients had received carbon-ion therapy[7]

Particle beams offer benefits over conventional photon radiation for the treatment of many tumors. Currently, 49 facilities worldwide— including 14 in the US—are producing proton beams, and another 29 are under construction. But carbon-ion therapy, which can benefit patients with deepseated or radiation-resistant tumors, remains in relative infancy, with eight centers operating and four under construction as of 1 April.[citation needed]

Carbon-ion treatment centers in operation

The Particle Therapy Co-Operative Group lists treatment centers in operation or in the planning or construction stage.[5] At least five centers using carbon ions are in operation, four in Japan: the HIMAC[9] at Chiba, the HIBMC[10] at Hyogo, and Gunma University's Heavy Ion Medical Center in Maebashi, and SAGA-HIMAT, Tosu. A fifth in Japan is currently under construction, tentatively named "i-ROCK".[11] In Germany, treatment at the Gesellschaft für Schwerionenforschung (GSI)[12] in Darmstadt, which is primarily a physics laboratory, has been discontinued in 2008, but the new HIT[13] in Heidelberg, which is a dedicated facility, started in November 2009. The HIT facility is using robotic technology with sub millimeter precision to position the patients. Moreover, Heidelberg has developed and took into clinical operation in 2011 the first gantry worldwide for proton and ion beams. The rotating part of this structure has a weight of 600 tons. The CNAO in Pavia, Italy opened in 2011 and will be one of the most advanced centers[clarification needed] for particle therapy with hadrons. CNAO will combine precise dose delivery with highly accurate patient alignment based on stereoscopic X-ray imaging.[14] Sophisticated approaches in image-guided particle therapy (IGPT) augments the radiotherapy machines with imaging capabilities and the latest computer vision technology to increase accuracy of target localization and enable patient alignment accuracies of 0.5 mm and better. In January 2015 the Shanghai Proton and Heavy Ion Centre opened after successfully completing the clinical trials.[15] The Marburg ion treatment facility, MIT (Marburger Ionenstrahl Therapie) treated their first patient in October 2015.[16]

Therapeutic intervention: 
Disease(s): 

Cyberknife

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Cyberknife

From Wikipedia, the free encyclopedia

The CyberKnife is a frameless robotic radiosurgery system used for treating benign tumors, malignant tumors and other medical conditions.[1][2] The system was invented by John R. Adler, a Stanford University professor of neurosurgery and radiation oncology, and Peter and Russell Schonberg of Schonberg Research Corporation. It is made by the Accuray company headquartered in Sunnyvale, California.

The CyberKnife system is a method of delivering radiotherapy, with the intention of targeting treatment more accurately than standard radiotherapy.[3] The two main elements of the CyberKnife are:

  1. the radiation produced from a small linear particle accelerator (linac)
  2. a robotic arm which allows the energy to be directed at any part of the body from any direction
 
The main features of the CyberKnife system, shown on a Fanuc robot

Contents

Main features

Several generations of the CyberKnife system have been developed since its initial inception in 1990. There are two major features of the CyberKnife system that are different from other stereotactic therapy methods.

Robotic mounting

The first is that the radiation source is mounted on a general purpose industrial robot. The original CyberKnife used a Japanese Fanuc robot; however, the more modern systems use a German KUKA KR 240. Mounted on the Robot is a compact X-band linac that produces 6MV X-ray radiation. The linac is capable of delivering approximately 600 cGy of radiation each minute – a new 800 cGy / minute model was announced at ASTRO[4] 2007. The radiation is collimated using fixed tungsten collimators (also referred to as "cones") which produce circular radiation fields. At present the radiation field sizes are: 5, 7.5, 10, 12.5, 15, 20, 25, 30, 35, 40, 50 and 60 mm. ASTRO 2007 also saw the launch of the IRIS[4] variable-aperture collimator which uses two offset banks of six prismatic tungsten segments to form a blurred regular dodecagon field of variable size which eliminates the need for changing the fixed collimators. Mounting the radiation source on the robot allows near-complete freedom to position the source within a space about the patient. The robotic mounting allows very fast repositioning of the source, which enables the system to deliver radiation from many different directions without the need to move both the patient and source as required by current gantry configurations.

Image guidance

The second is that the CyberKnife system uses an image guidance system. X-ray imaging cameras are located on supports around the patient allowing instantaneous X-ray images to be obtained.

6D skull

The original (and still utilized) method is called 6D or skull based tracking. The X-ray camera images are compared to a library of computer generated images of the patient anatomy. Digitally Reconstructed Radiographs (or DRR's) and a computer algorithm determines what motion corrections have to be given to the robot because of patient movement. This imaging system allows the CyberKnife to deliver radiation with an accuracy of 0.5mm without using mechanical clamps attached to the patient's skull.[5] The use of the image-guided technique is referred to as frameless stereotactic radiosurgery. This method is referred to as 6D because corrections are made for the 3 translational motions (X,Y and Z) and three rotational motions. It should be noted that it is necessary to use some anatomical or artificial feature to orient the robot to deliver X-ray radiation, since the tumor is never sufficiently well defined (if visible at all) on the X-ray camera images.

 
6D skull tracking

Xsight

Additional image guidance methods are available for spinal tumors and for tumors located in the lung. For a tumor located in the spine, a variant of the image guidance called Xsight-Spine[6] is used. The major difference here is that instead of taking images of the skull, images of the spinal processes are used. Whereas the skull is effectively rigid and non-deforming, the spinal vertebrae can move relative to each other, this means that image warping algorithms must be used to correct for the distortion of the X-ray camera images.

A recent enhancement to Xsight is Xsight-Lung[7] which allows tracking of some lung tumors without the need to implant fiducial markers.[8]

Fiducial

For soft tissue tumors, a method known as fiducial tracking can be utilized.[9] Small metal markers (fiducials) made out of gold for bio-compatibility and high density to give good contrast on X-ray images are surgically implanted in the patient. This is carried out by an interventional radiologist, or neurosurgeon. The placement of the fiducials is a critical step if the fiducial tracking is to be used. If the fiducials are too far from the location of the tumor, or are not sufficiently spread out from each other it will not be possible to accurately deliver the radiation. Once these markers have been placed, they are located on a CT scan and the image guidance system is programmed with their position. When X-ray camera images are taken, the location of the tumor relative to the fiducials is determined, and the radiation can be delivered to any part of the body. Thus the fiducial tracking does not require any bony anatomy to position the radiation. Fiducials are known however to migrate and this can limit the accuracy of the treatment if sufficient time is not allowed between implantation and treatment for the fiducials to stabilize.[10][11]

Synchrony

 
CyberKnife Machine

Another technology of image guidance that the CyberKnife system can use is called the Synchrony system or Synchrony method. This method uses a combination of surgically placed internal fiducials (typically small gold markers, well visible in x-ray imaging), and light emitting optical fibers (LED markers) mounted on the patient skin. LED markers are tracked by an infrared tracking camera. Since the tumor is moving continuously, to continuously image its location using X-ray cameras would require prohibitive amounts of radiation to be delivered to the patient's skin. The Synchrony system overcomes this by periodically taking images of the internal fiducials, and computing a correlation model between the motion of the external LED markers and the internal fiducials. Time stamps from the two sensors (x-ray and infrared LED) are needed to synchronize the two data streams, hence the name Synchrony.

Motion prediction is used to overcome the motion latency of the robot and the latency of image acquisition. Before treatment, a computer algorithm creates a correlation model that represents how the internal fiducial markers are moving compared to the external markers. During treatment, the system continuously infers the motion of the internal fiducials, and therefore the tumor, based on the motion of the skin markers. The correlation model is updated at fixed time steps during treatment. Thus, the Synchrony tracking method makes no assumptions about the regularity or reproducibility of the patient breathing pattern.

To function properly, the system requires that for any given correlation model there is a functional relationship between the markers and the internal fiducials. The external marker placement is also important, and the markers are usually placed on the patient abdomen so that their motion will reflect the internal motion of the diaphragm and the lungs. This method was invented in 1998.[12][13] The first patients were treated at Cleveland Clinic in 2002. Synchrony is utilized primarily for tumors that are in motion while being treated, such as lung tumors and pancreatic tumors.[14][15]

RoboCouch

A robotic six degree of freedom patient treatment couch called RoboCouch[16] improves patient positioning options for treatment.

Frameless

The frameless nature of the CyberKnife also increases the clinical efficiency. In conventional frame-based radiosurgery, the accuracy of treatment delivery is determined solely by connecting a rigid frame to the patient which is anchored to the patient’s skull with invasive aluminum or titanium screws. The CyberKnife is the only radiosurgery device that does not require such a frame for precise targeting.[17] Once the frame is connected, the relative position of the patient anatomy must be determined by making a CT or MRI scan. After the CT or MRI scan has been made, a radiation oncologist must plan the delivery of the radiation using a dedicated computer program, after which the treatment can be delivered, and the frame removed. The use of the frame therefore requires a linear sequence of events that must be carried out sequentially before another patient can be treated. Staged CyberKnife radiosurgery is of particular benefit to patients who have previously received large doses of conventional radiation therapy and patients with gliomas located near critical areas of the brain. Unlike whole brain radiotherapy, which must be administered daily over several weeks, radiosurgery treatment can usually be completed in 1–5 treatment sessions. Radiosurgery can be used alone to treat brain metastases, or in conjunction with surgery or whole brain radiotherapy, depending on the specific clinical circumstances.[18]

By comparison, using a frameless system, a CT scan can be carried out on any day prior to treatment that is convenient. The treatment planning can also be carried out at any time prior to treatment. During the treatment the patient need only be positioned on a treatment table and the predetermined plan delivered. This allows the clinical staff to plan many patients at the same time, devoting as much time as is necessary for complicated cases without slowing down the treatment delivery. While a patient is being treated, another clinician can be considering treatment options and plans, and another can be conducting CT scans.

In addition, very young patients (pediatric cases) or patients with fragile heads because of prior brain surgery cannot be treated using a frame based system. Also, by being frameless the CyberKnife can efficiently re-treat the same patient without repeating the preparation steps that a frame-based system would require.

The delivery of a radiation treatment over several days or even weeks (referred to as fractionation) can also be beneficial from a therapeutic point of view. Tumor cells typically have poor repair mechanisms compared to healthy tissue, so by dividing the radiation dose into fractions the healthy tissue has time to repair itself between treatments.[19] This can allow a larger dose to be delivered to the tumor compared to a single treatment.[20]

Clinical uses

Since August 2001, the CyberKnife system has FDA clearance for treatment of tumors in any location of the body.[21] Some of the tumors treated include: pancreas,[15][22] liver,[23] prostate,[24][25] spinal lesions,[26] head and neck cancers,[27] and benign tumors.[28]

None of these studies have shown any general survival benefit over conventional treatment methods. By increasing the accuracy with which treatment is delivered there is a potential for dose escalation, and potentially a subsequent increase in effectiveness, particularly in local control rates. However the studies cited are so far limited in scope, and more extensive research will need to be completed in order to show any effects on survival.[22]

In 2008 actor Patrick Swayze was among the people to be treated with CyberKnife radiosurgery.[29]

Locations

CyberKnife systems have been installed in over 150 locations,[30] including 100 hospitals in the United States.[31]

Recently – April 2014 – CyberKnife has been installed at Sir Charles Gairdner Hospital, Perth, Australia.[32]

Stanford University has treated over 2,500 patients using the Cyberknife system, and worldwide over 40,000 patients have been treated.[33]

See also

References

 

Therapeutic intervention: 
Disease(s): 

PSMA - Lutetium Treatment

field_vote: 

Lutetium-177 linked to PSMA: an update

 
 
 
 
 
 
5 Votes

 

One of the more important emerging forms of radiotherapy for metastatic castrate-resistant prostate cancer (mCRPC) is the radioactive element lutetium-177 (177Lu) chemically bonded to a ligand — an antibody or a small molecule that attaches to the prostate-specific membrane antigen (PSMA). We’ll call this class of medications [177Lu]PSMA.

PSMA is expressed on the surface of 95 percent of all metastatic prostate cancer cells; see this link for a fuller explanation. Many of the studies on [177Lu]PSMA have been conducted in Germany. Recently, we reported on a small study from Bad Berka, Germany, with some early encouraging results. There have been a few more trial reports since then.

All of the more recently published studies used a ligand called PSMA-617, a small molecule that attaches to PSMA, rather than a PSMA antibody. It was hoped that this ligand would be more specific to prostate cancer cells, with less affinity for salivary glands and kidneys where it can cause side effects and false positives.

Kratchowil et al. at the University of Heidelberg reported on 30 patients treated with one to three cycles of [177Lu]PSMA-617.

  • PSA decreased in 21/30 patients (70 percent).
    • PSA decreased by > 50 percent in 13/30 patients (43 percent)
    • 8/11 patients (73 percent) who had three cycles of therapy had PSA declines >50 percent that were sustained for over 24 weeks; the number and size of their metastases decreased as well.
  • Hematotoxicity (from bone marrow suppression) was mild.
  • Xerostomia (dry mouth), nausea and fatigue were transient and occurred in < 10 percent.
  • Excess radioactivity was cleared from the kidneys within 48 hours.

Rahbar et al. at the University Hospital Münster (again in Germany) reported on 74 patients treated with a single dose of [177Lu]PSMA-617.

  • PSA decreased in 47/74 patients (64 percent).
    • PSA decreased by > 50 percent in 23/74 patients (31 percent)
  • PSA was stable (−50 percent to +25 percent) in 35/74 patients (47 percent)
  • PSA increased by > 25 percent in 17/74 patients (23 percent)
  • No significant loss of red blood cells, white blood cells, or kidney function
  • Mild decline in platelets, but within normal range

Rahbar et al. also report outcomes on 28 patients after one vs. two treatments.

  • PSA decreased in 59 percent of patients after one treatment and in 75 percent after two treatments.
    • PSA decreased by > 50 percent in 32 percent of patients after one treatment and in 50 percent after two treatments.
  • Median survival was 29 weeks, compared to 20 weeks based on historical expectations.
  • No clinically significant or lasting toxicity occurred.

Radiotherapy with 177Lu, though encouraging, is still in its early days. There is much work to be done in identifying the optimal ligand, optimal dose, optimal number of treatments, optimal patient/disease characteristics, and adjuvant therapies. We encourage participation in clinical trials in the US (see NCT00859781) and in Germany.

Editorial note: This commentary was written for The “New” Prostate Cancer InfoLink by Allen Edel.

Therapeutic Substance(s): 
Therapeutic intervention: 

Proton Therapy

field_vote: 

Proton therapy

From Wikipedia, the free encyclopedia
 
Proton therapy equipment at the Mayo Clinic in Rochester, Minnesota

Proton therapy, or proton beam therapy, is a medical procedure, a type of particle therapy that uses a beam of protons to irradiate diseased tissue, most often in the treatment of cancer. The chief advantage of proton therapy over other types of external beam radiotherapy is that as a charged particle the dose is deposited over a narrow range and there is minimal exit dose.

Contents

Description

 
In a typical treatment plan for proton therapy, the spread out Bragg peak (SOBP, dashed blue line) is the therapeutic radiation distribution. The SOBP is the sum of several individual Bragg peaks (thin blue lines) at staggered depths. The depth-dose plot of an X-ray beam (red line) is provided for comparison. The pink area represents additional doses of X-ray radiotherapy—which can damage normal tissues and cause secondary cancers, especially of the skin.[1]

Proton therapy is a type of external beam radiotherapy that uses ionizing radiation. In proton therapy, medical personnel use a particle accelerator to target a tumor with a beam of protons.[2][3] These charged particles damage the DNA of cells, ultimately killing them or stopping their reproduction. Cancerous cells are particularly vulnerable to attacks on DNA because of their high rate of division and their reduced abilities to repair DNA damage.

Because of their relatively large mass, protons have little lateral side scatter in the tissue; the beam does not broaden much, stays focused on the tumor shape and delivers only low-dose side effects to surrounding tissue. All protons of a given energy have a certain range; very few protons penetrate beyond that distance.[4] Furthermore, the dose delivered to tissue is maximized only over the last few millimeters of the particle’s range; this maximum is called the Bragg peak, often referred to as the SOBP.[5]

To treat tumors at greater depths, the proton accelerator must produce a beam with higher energy, typically given in eV or electron volts. Proton therapy treats tumors closer to the surface of the body with lower energy protons. Accelerators used for proton therapy typically produce protons with energies in the range of 70 to 250 MeV. Adjusting proton energy during the treatment maximizes the cell damage the proton beam causes within the tumor. Tissue closer to the surface of the body than the tumor receives reduced radiation, and therefore reduced damage. Tissues deeper in the body receive very few protons, so the dosage becomes immeasurably small.[4]

In most treatments, protons of different energies with Bragg peaks at different depths are applied to treat the entire tumor. These Bragg peaks are shown as thin blue lines in the figure to the right. The total radiation dosage of the protons is called the spread-out Bragg peak (SOBP), shown as a heavy dashed blue line in figure to the right. It is important to understand that, while tissues behind or deeper than the tumor receive almost no radiation from proton therapy, the tissues in front of or shallower than the tumor receive radiation dosage based on the SOBP.

History

The first suggestion that energetic protons could be an effective treatment method was made by Robert R. Wilson[6] in a paper published in 1946 while he was involved in the design of the Harvard Cyclotron Laboratory (HCL).[7] The first treatments were performed with particle accelerators built for physics research, notably Berkeley Radiation Laboratory in 1954 and at Uppsala in Sweden in 1957. In 1961, a collaboration began between HCL and the Massachusetts General Hospital (MGH) to pursue proton therapy. Over the next 41 years, this program refined and expanded these techniques while treating 9,116 patients[8] before the cyclotron was shut down in 2002. The world's first hospital-based proton therapy center was a low energy cyclotron centre for ocular tumours at the Clatterbridge Centre for Oncology in the UK, opened in 1989,[9] followed in 1990 at the Loma Linda University Medical Center (LLUMC) in Loma Linda, California. Later, The Northeast Proton Therapy Center at Massachusetts General Hospital was brought online, and the HCL treatment program was transferred to it during 2001 and 2002. By 2010 these facilities were joined by an additional seven regional hospital-based proton therapy centers in the United States alone, and many more worldwide.[10]

Application

Physicians use protons to treat conditions in two broad categories:

  • Disease sites that respond well to higher doses of radiation, i.e., dose escalation. In some instances, dose escalation has demonstrated a higher probability of "cure" (i.e., local control) than conventional radiotherapy.[11] These include, among others, uveal melanoma (ocular tumors), skull base and paraspinal tumors (chondrosarcoma and chordoma), and unresectable sarcomas. In all these cases proton therapy achieves significant improvements in the probability of local control over conventional radiotherapy.[12][13][14] In treatment of ocular tumors, proton therapy also has high rates of maintaining the natural eye.[15]

The second broad class are those treatments where proton therapy's increased precision reduces unwanted side effects by lessening the dose to normal tissue. In these cases, the tumor dose is the same as in conventional therapy, so there is no expectation of an increased probability of curing the disease. Instead, the emphasis is on reducing the integral dose to normal tissue, thus reducing unwanted effects.[11]

Two prominent examples are pediatric neoplasms (such as medulloblastoma) and prostate cancer. In the case of pediatric treatments, a 2004 review gave theoretical advantages but did not report any clinical benefits.[16][17]

In prostate cancer cases, the issue is less clear. Some published studies found a reduction in long term rectal and genito-urinary damage when treating with protons rather than photons (meaning X-ray or gamma ray therapy). Others showed a small difference, limited to cases where the prostate is particularly close to certain anatomical structures.[18][19] The relatively small improvement found may be the result of inconsistent patient set-up and internal organ movement during treatment, which offsets most of the advantage of increased precision.[19][20][20][21] One source suggests that dose errors around 20% can result from motion errors of just 2.5 mm,[citation needed] and another that prostate motion is between 5–10 mm.[22]

However, the number of cases of prostate cancer diagnosed each year far exceeds those of the other diseases referred to above, and this has led some, but not all, facilities to devote a majority of their treatment slots to prostate treatments. For example, two hospital facilities devote roughly 65%[23] and 50%[24] of their proton treatment capacity to prostate cancer, while a third devotes only 7.1%.[25]

Overall worldwide numbers are hard to compile, but one example in the literature shows that in 2003 roughly 26% of proton therapy treatments worldwide were for prostate cancer.[26] Proton therapy for ocular (eye) tumors is a special case since this treatment requires only comparatively low energy protons (about 70 MeV). Owing to this low energy requirement, some particle therapy centers only treat ocular tumors.[8] Proton, or more generally, hadron therapy of tissue close to the eye affords sophisticated methods to assess the alignment of the eye that can vary significantly from other patient position verification approaches in image guided particle therapy.[27] Position verification and correction must ensure that the radiation spares sensitive tissue like the optic nerve to preserve the patient’s vision.

Comparison with other treatments

The issue of when, whether, and how best to apply this technology is controversial.[28][29][30] As of 2012 there have been no controlled trials to demonstrate that proton therapy yields improved survival or other clinical outcomes (including impotence in prostate cancer) compared to other types of radiation therapy, although a five-year study of prostate cancer is underway at Massachusetts General Hospital.[31][32][33][34][34] Proton therapy is far more expensive than conventional therapy.[29][35] As of 2012 proton therapy required a very large capital investment (from US$100M to more than $180M).[28][30][36]

Preliminary results from a 2009 study, including high-dose treatments, showed very few side effects.[37]

NHS Choices has stated:

We cannot say with any conviction that proton beam therapy is “better” overall than radiotherapy. (...) Some overseas clinics providing proton beam therapy heavily market their services to parents who are understandably desperate to get treatment for their children. Proton beam therapy can be very costly and it is not clear whether all children treated privately abroad are treated appropriately.[38][39]

X-ray radiotherapy

 
Irradiation of nasopharyngeal carcinoma by photon (X-ray) therapy (left) and proton therapy (right)

The figure at the right of the page shows how beams of X-rays (IMRT; left frame) and beams of protons (right frame), of different energies, penetrate human tissue. A tumor with a sizable thickness is covered by the IMRT spread out Bragg peak (SOBP) shown as the red lined distribution in the figure. The SOBP is an overlap of several pristine Bragg peaks (blue lines) at staggered depths.

Megavoltage X-ray therapy has less "skin scarring potential" than proton therapy: X-ray radiation at the skin, and at very small depths, is lower than for proton therapy. One study estimates that passively scattered proton fields have a slightly higher entrance dose at the skin (~75%) compared to therapeutic megavoltage (MeV) photon beams (~60%).[1] X-ray radiation dose falls off gradually, unnecessarily damaging tissue deeper in the body and damaging the skin and surface tissue opposite the beam entrance. The differences between the two methods depends on the:

  • Width of the SOBP
  • Depth of the tumor
  • Number of beams that treat the tumor

The X-ray advantage of reduced damage to skin at the entrance is partially counteracted by damage to skin at the exit point.

Since X-ray treatments are usually done with multiple exposures from opposite sides, each section of skin is exposed to both entering and exiting X-rays. In proton therapy, skin exposure at the entrance point is higher, but tissues on the opposite side of the body to the tumor receive no radiation. Thus, X-ray therapy causes slightly less damage to the skin and surface tissues, and proton therapy causes less damage to deeper tissues in front of and beyond the target.[3]

An important consideration in comparing these treatments is whether the equipment delivers protons via the scattering method (historically, the most common) or a spot scanning method. Spot scanning can adjust the width of the SOBP on a spot-by-spot basis, which reduces the volume of normal (healthy) tissue inside the high dose region. Also, spot scanning allows for intensity modulated proton therapy (IMPT), which determines individual spot intensities using an optimization algorithm that lets the user balance the competing goals of irradiating tumors while sparing normal tissue. Spot scanning availability depends on the machine and the institution. Spot scanning is more commonly known as pencil-beam scanning and is available on IBA, Hitachi, Mevion (known as hyperscan [40] and not US FDA approved as of 2015) and Varian.

Surgery

Physicians base the decision to use surgery or proton therapy (or any radiation therapy) on the tumor type, stage, and location. In some instances, surgery is superior (e.g. cutaneous melanoma), in some instances radiation is superior (e.g., skull base chondrosarcoma), and in some instances they are comparable (e.g., prostate cancer). In some instances, they are used together (e.g., rectal cancer or early stage breast cancer). The benefit of external beam proton radiation lies in the dosimetric difference from external beam X-ray radiation and brachytherapy in cases where the use of radiation therapy is already indicated, rather than as a direct competition with surgery.[11] However, in the case of prostate cancer, the most common indication for proton beam therapy, no clinical study directly comparing proton therapy to surgery, brachytherapy, or other treatments has shown any clinical benefit for proton beam therapy. Indeed, the largest study to date showed that IMRT compared with proton therapy was associated with less gastrointestinal morbidity.[41]

Side effects and risks

Proton therapy is a type of external beam radiotherapy, and shares risks and side effects of other forms of radiation therapy. However the dose outside of the treatment region can be significantly less for deep-tissue tumors than X-ray therapy, because proton therapy takes full advantage of the Bragg peak. Proton therapy has been in use for over 40 years, and is a mature treatment technology. However, as with all medical knowledge, understanding of the interaction of radiation (proton, X-ray, etc.) with tumor and normal tissue is still imperfect.[28]

Costs

Historically, proton therapy has been expensive. Goitein & Jermann's[42] analysis had previously determined the relative cost of proton therapy is approximately 2.4 times that of X-ray therapies. However, newer, more compact proton beam sources can be four to five times cheaper and offer more accurate three-dimensional targeting.[43][44] Thus the cost is expected to reduce as better proton technology becomes more widely available. A similar analysis by Lievens & Van den Bogaert[45] determined that the cost of proton therapy is not unrealistic and should not be the reason for denying patients access to this technology. In some clinical situations, proton beam therapy is clearly superior to the alternatives.[46][47] Another study in 2007 expressed concerns about the effectiveness of proton therapy for treating prostate cancer.[48] Although, with the advent of new developments in proton beam technology, such as improved scanning techniques and more precise dose delivery ('pencil beam scanning'), this situation may change considerably.[49] Amitabh Chandra, a health economist at Harvard University, has been quoted as saying that "Proton-beam therapy is like the death star of American medical technology... It's a metaphor for all the problems we have in American medicine.”[50] However, another study has shown that proton therapy in fact brings cost savings.[51] The advent of second generation, and much less expensive, proton therapy equipment now being installed at various sites may change this picture significantly.[52]

Treatment centers

 
Control panel of the synchrocyclotron at the Orsay proton therapy center, France

As of January 2016, there are over 45 particle therapy facilities worldwide.[53] This represents a total of more than 121 treatment rooms available to patients.[54] More than 96,537 patients had been treated.[55]

One hindrance to universal use of the proton in cancer treatment is the size and cost of the cyclotron or synchrotron equipment necessary. Several industrial teams are working on development of comparatively small accelerator systems to deliver the proton therapy to patients.[56] Among the technologies being investigated are superconducting synchrocyclotrons (also known as FM Cyclotrons), ultra-compact synchrotrons, dielectric wall accelerators,[56] and linear particle accelerators.[44]

United States

Proton treatment centers in the United States as of 2017 (in chronological order of first treatment date) include:[9][57]

InstitutionLocationYear of first treatmentComments
University of California, Davis, Crocker Nuclear Laboratory[58] Davis, CA 1994 Ocular treatments only (low energy accelerator)
Loma Linda University Medical Center[59] Loma Linda, CA 1990 First hospital-based facility in USA It uses the Spread Out Bragg's Peak (SOBP) shown in the above illustration.
Francis H. Burr Proton Center (formerly NPTC) at Massachusetts General Hospital (MGH) Boston, MA 2001 Continuation of Harvard Cyclotron Laboratory/MGH treatment program that began in 1961
SCCA Proton Therapy Center at Seattle Cancer Care Alliance Seattle, WA 2001 Part of Fred Hutchinson Cancer Research Center
Indiana University Health Proton Therapy Center Bloomington, IN 2004 Formerly MPRI (Closed 4December 2014)
University of Florida Health Proton Therapy Institute-Jacksonville[60] Jacksonville, FL 2006 The UF Health Proton Therapy Institute is a part of a non-profit academic medical research facility. It is the first treatment center in the Southeast U.S. to offer proton therapy.
University of Texas MD Anderson Cancer Center[61] Houston, TX 2006  
ProCure Proton Therapy Center of Oklahoma[62] Oklahoma City, OK 2009 First of a number of planned ProCure facilities
CDH Proton Center[63] Warrenville, IL 2010 Second of a number of planned ProCure facilities
Roberts Proton Therapy Center, University of Pennsylvania Health System[64] Philadelphia, PA 2010 The largest proton therapy center in the world, the Roberts Proton Therapy Center, which is a part of Penn's Abramson Cancer Center, is also part of a medical complex that includes the Hospital of the University of Pennsylvania, the Perelman Center for Advanced Medicine, and the Children's Hospital of Philadelphia.
Hampton University Proton Therapy Institute Hampton, VA 2010  
ProCure Proton Therapy Center[65] Somerset, NJ 2012 Third of a number of planned ProCure facilities
Siteman Cancer Center[43] St. Louis, MO 2013 First of the new single suite, ultra-compact, superconducting synchrocyclotron,[66] lower cost facilities to treat a patient using the Mevion Medical system's S250.[67]
Provision Proton Therapy Center[68] Knoxville, TN 2014
Scripps Health Scripps Proton Therapy Center [69] San Diego, CA 2014 (5 suites, all using pencil-beam scanning precision also called IMPT) Manufactured by Varian Medical Systems [70]
Ackerman Cancer Center Jacksonville, FL 2015 Ackerman Cancer Center is the world's first private, physician-owned practice to provide proton therapy, in addition to conventional radiation therapy and on-site diagnostic services.
The Laurie Proton Therapy Center, Robert Wood Johnson University Hospital New Brunswick, NJ 2015 The Laurie Proton Therapy Center is home to the world’s third MEVION S250 Proton Therapy System.
Texas Center for Proton Therapy Dallas Fort Worth, Texas 2015 TCPT is a joint venture between Baylor, McKesson, and Texas Oncology. It has three pencil beam rooms and cone beam CT imaging.
Mayo Clinic Cancer Center Phoenix, Arizona 2016 4 treatment rooms, Mayo Clinic Cancer Center Officially opened its doors in February 2016.
Mayo Clinic Jacobson Building Rochester, MN 2016 4 treatment rooms, [2], officially opened its doors in May 2015.
The Marjorie and Leonard Williams Center for Proton Therapy Orlando, Florida 2016 http://www.ufhealthcancerorlando.com/centers/proton-therapy-center Opened its doors in April 2016.
Collaborative Effort: University of Cincinnati Cancer Institute; Cincinnati Childrens Hospital Medical Center Liberty Township, Ohio 2016 http://uchealth.com/cancer/centers-programs/proton-therapy/

https://www.cincinnatichildrens.org/service/p/proton-therapy

MFG: Varian Medical Systems, Operational As Of Sept 2016

Maryland Proton Treatment Center Baltimore, MD 2016 5 treatment rooms, all using pencil-beam scanning. Maryland Proton Treatment Center is affiliated with the University of Maryland Greenebaum Comprehensive Cancer Center.
The Baptist Health of South Florida Miami Cancer Institute (coming soon) Miami, Florida 2017 https://baptisthealth.net/en/health-services/cancer-services/pages/proton-therapy.aspx

Outside the USA

Protontherapy Centres (partial list)[9]
InstitutionMaximum energy (MeV)Year of first treatmentLocationCountry
TRIUMF[71] 74 1995 Vancouver  Canada
Clatterbridge Cancer Centre NHS Foundation Trust, low-energy for ocular[72] 62 1989 Liverpool  United Kingdom
Heidelberg Ion-Beam Therapy Center (HIT) Heidelberg 230 2009 Heidelberg  Germany
Westdeutsches Protonentherapiezentrum Essen 230 2013 Essen  Germany
Helmholtz-Zentrum Berlin in Cooperation with Charité 72 1998 Berlin  Germany
RPTC Rinecker Proton Therapy Center 250 2009 Munich  Germany
PTC Uniklinikum Dresden 230 2014 Dresden  Germany
Wanjie Proton Therapy Center 230 2004 Zibo  China
Proton Medical Research Center University of Tsukuba 250 2001 Tsukuba  Japan
Research Center for Charged Particle Therapy (NIRS) 350-400 1994 Chiba  Japan
Centre de protonthérapie de l'Institut Curie 235 1991 Orsay  France
Centre Antoine Lacassagne 63 1991 Nice  France
Paul Scherrer Institute 250 1984 Villigen   Switzerland
Instytut Fizyki Jądrowej PAN 60 2011 Kraków  Poland
Centrum Cyklotronowe Bronowice 230 2015 Kraków  Poland
Centro per la protonterapia 230 2014 Trento  Italy
Centro Nazionale di Adroterapia Oncologica 250 2011 Pavia  Italy
Proton Therapy Center, Prague 230 2012 Prague  Czech Republic
Shanghai Proton and Heavy Ion Center 230 2014 Shanghai  China
Proton Therapy Center, Korea National Cancer Center 230 2007 Seoul  Korea
Proton and Radiation Therapy Center, Linkou Chang Gung Memorial Hospital 230 2015 Taipei  Taiwan
A. Tsyb Medical Radiological Research Centre 250 2016 Obninsk  Russia
HPTC - Holland Particle Therapy Centre 230 2017 Delft  Netherlands
GPTC - UMC Groningen Protonen Therapie Centrum 230 2018 Groningen  Netherlands

United Kingdom

In 2013 the British government announced that £250 million had been budgeted to establish two centers for advanced radiotherapy, to open in 2018 at the Christie Hospital NHS Foundation Trust in Manchester and University College London Hospitals NHS Foundation Trust. These would offer high-energy proton therapy, currently unavailable in the UK, as well as other types of advanced radiotherapy, including intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT).[73] In 2014, only low-energy proton therapy was available in the UK, at the Clatterbridge Cancer Centre NHS Foundation Trust in Merseyside. But NHS England has paid to have suitable cases treated abroad, mostly in the US. Such cases have risen from 18 in 2008 to 122 in 2013, 99 of whom were children. The cost to the National Health Service averaged around £100,000 per case.[74]

In January 2015, it was announced the UK would get its first high energy proton beam therapy centre a year earlier than expected.[75] A company named Advanced Oncotherapy signed a deal with Howard de Walden Estate to install a machine in Harley Street, the heart of private medicine in London, to be ready by 2017.[76] The company promises that its use of a linear accelerator allows for facilities one-third smaller and one-fifth the cost of facilities based on existing cyclotron designs. The NHS has been criticised by some doctors for buying "old" equipment.[77]

Proton Partners International is developing three centres in Newport, Wales, Bomarsund, Northumberland, and Reading, Berkshire which are expected to open in 2017.[78]

See also

References

  1. "Construction begins on UK's first proton beam therapy cancer treatment centre". Wales on line. 18 January 2016. Retrieved 24 December 2016.

Further reading

  • Greco C.; Wolden S. (Apr 2007). "Current status of radiotherapy with proton and light ion beams". Cancer. 109 (7): 1227–38. doi:10.1002/cncr.22542. PMID 17326046.
  • "Use of Protons for Radiotherapy", A.M. Koehler, Proc. of the Symposium on Pion and Proton Radiotherapy, Nat. Accelerator Lab., (1971).
  • A.M. Koehler, W.M. Preston, "Protons in Radiation Therapy: comparative Dose Distributions for Protons, Photons and Electrons Radiology 104(1):191–195 (1972).
  • "Bragg Peak Proton Radiosurgery for Arteriovenous Malformation of the Brain" R.N. Kjelberg, presented at First Int. Seminar on the Use of Proton Beams in Radiation Therapy, Moskow (1977).
  • Austin-Seymor, M.J. Munzenrider, et al. "Fractionated Proton Radiation Therapy of Cranial and Intracrainial Tumors" Am. J. of Clinical Oncology 13(4):327–330 (1990).
  • "Proton Radiotherapy", Hartford, Zietman, et al. in Radiotheraputic Management of Carcinoma of the Prostate, A. D'Amico and G.E. Hanks. London,UK, Arnold Publishers: 61–72 (1999).

External links

Therapeutic intervention: 

Radiofrequency ablation

field_vote: 

Radiofrequency ablation

From Wikipedia, the free encyclopedia
Radiofrequency ablation
Intervention
ICD-9-CM 01.32, 04.2, 37.33, 37.34, 60.97
MeSH D017115

Radiofrequency ablation (RFA) is a medical procedure in which part of the electrical conduction system of the heart, tumor or other dysfunctional tissue is ablated using the heat generated from medium frequency alternating current (in the range of 350–500 kHz).[1] RFA is generally conducted in the outpatient setting, using either local anesthetics or conscious sedation anesthesia. When it is delivered via catheter, it is called radiofrequency catheter ablation.

Two important advantages of radio frequency current (over previously used low frequency AC or pulses of DC) are that it does not directly stimulate nerves or heart muscle and therefore can often be used without the need for general anesthetic, and that it is very specific for treating the desired tissue without significant collateral damage.[citation needed]

Documented benefits have led to RFA becoming widely used during the last 15 years.[2][3] RFA procedures are performed under image guidance (such as X-ray screening, CT scan or ultrasound) by an interventional pain specialist (such as an anesthesiologist), interventional radiologist, otolaryngologists, a gastrointestinal or surgical endoscopist, or a cardiac electrophysiologist, a subspecialty of cardiologists.

Contents

Tumors

 
CT scan showing radiofrequency ablation of a liver lesion

RFA may be performed to treat tumors in the lung,[4][5][6] liver,[7] kidney, and bone, as well as other body organs less commonly. Once the diagnosis of tumor is confirmed, a needle-like RFA probe is placed inside the tumor. The radiofrequency waves passing through the probe increase the temperature within tumor tissue and results in destruction of the tumor. RFA can be used with small tumors, whether these arose within the organ (primary tumors) or spread to the organ (metastases). The suitability of RFA for a particular tumor depends on multiple factors.

RFA can usually be administered as an out-patient procedure, though may at times require a brief hospital stay. RFA may be combined with locally delivered chemotherapy to treat hepatocellular carcinoma (primary liver cancer). A method currently in phase III trials uses the low-level heat (hyperthermia) created by the RFA probe to trigger release of concentrated chemotherapeutic drugs from heat-sensitive liposomes in the margins around the ablated tissue as a treatment for Hepatocellular carcinoma (HCC).[8] Radiofrequency ablation is also used in pancreatic cancer and bile duct cancer.[9]

RFA has become increasingly important in the care of benign bone tumors, most notably osteoid osteomas. Since the procedure was first introduced for the treatment of osteoid osteomas in the 1990s,[10] it has been shown in numerous studies to be less invasive and expensive, to result in less bone destruction and to have equivalent safety and efficacy to surgical techniques, with 66 to 95% of patients reporting freedom from symptoms.[11][12][13] While initial success rates with RFA are high, symptom recurrence after RFA treatment has been reported, with some studies demonstrating a recurrence rate similar to that of surgical treatment.[14] RFA is also increasingly used in the palliative treatment of painful metastatic bone disease in patients who are not eligible or do not respond to traditional therapies ( i.e. radiation therapy, chemotherapy, palliative surgery, bisphosphonates or analgesic medications).[15]

Cardiology

 
Schematic view of a pulmonary vein ablation. The catheter reaches (from below) through the inferior vena cava, the right atrium and the left atrium, to the orifice of the left upper pulmonary vein.

Radiofrequency energy is used in heart tissue or normal parts to destroy abnormal electrical pathways that are contributing to a cardiac arrhythmia. It is used in recurrent atrial flutter (Afl), atrial fibrillation (AF), supraventricular tachycardia (SVT), atrial tachycardia, Multifocal Atrial Tachycardia (MAT) and some types of ventricular arrhythmia. The energy-emitting probe (electrode) is at the tip of a catheter which is placed into the heart, usually through a vein. This catheter is called the ablator. The practitioner first "maps" an area of the heart to locate the abnormal electrical activity (electrophysiology study) before the responsible tissue is eliminated. Ablation is now the standard treatment for SVT and typical atrial flutter and the technique can also be used in AF, either to block the atrioventricular node after implantation of a pacemaker or to block conduction within the left atrium, especially around the pulmonary veins. In some conditions, especially forms of intra-nodal re-entry (the most common type of SVT), also called atrioventricular nodal reentrant tachycardia or AVNRT, ablation can also be accomplished by cryoablation (tissue freezing using a coolant which flows through the catheter) which avoids the risk of complete heart block - a potential complication of radiofrequency ablation in this condition. Recurrence rates with cryoablation are higher, though.[16] Microwave ablation, where tissue is ablated by the microwave energy "cooking" the adjacent tissue, and ultrasonic ablation, creating a heating effect by mechanical vibration, or laser ablation have also been developed but are not in widespread use.

In 2004, former British prime minister Tony Blair underwent radiofrequency catheter ablation for recurrent atrial flutter.[17][18]

In AF, the abnormal electrophysiology can also be corrected surgically. This procedure, referred to as the "Cox maze procedure", is mostly performed concomitantly with cardiac surgery.

A new and promising indication for the use of radiofrequency technology has made news in the last few years. Hypertension is a very common condition, with about 1 billion people over the world, nearly 75 million in the US alone. Complications of inadequately controlled hypertension are many and have both individual and global impact. Treatment options include medications, diet, exercise, weight reduction and meditation. Inhibition of the neural impulses that are believed to cause or worsen hypertension has been tried for a few decades. Surgical sympathectomy has helped but not without significant side effects. Therefore, the introduction of non-surgical means of renal denervation with radiofrequency ablation catheter was enthusiastically welcomed. Although, the initial use of radiofrequency-generated heat to ablate nerve endings in the renal arteries to aid in management of 'resistant hypertension' were encouraging, the most recent phase 3 studying looking at catheter-based renal denervation for the treatment of resistant hypertension failed to show any significant reduction in systolic blood pressure.[19]

Aesthetics dermatology

Radiofrequency ablation[20] is a dermatosurgical procedure by using various forms of alternating current. Types of radiofrequency are electrosection, electrocoagulation, electrodessication and fulguration. The use of radiofrequency ablation has obtained importance as it can be used to treat most of the skin lesions with minimal side effects and complications.

Varicose veins

Radiofrequency ablation is a minimally invasive procedure used in the treatment of varicose veins. It is an alternative to the traditional stripping operation. Under ultrasound guidance, a radiofrequency catheter is inserted into the abnormal vein and the vessel treated with radio-energy, resulting in closure of the involved vein. Radiofrequency ablation is used to treat the great saphenous vein, the small saphenous vein, and the perforator veins. The latter are connecting veins that transport blood from the superficial veins to the deep veins. Branch varicose veins are then usually treated with other minimally invasive procedures, such as ambulatory phlebectomy, sclerotherapy, or foam sclerotherapy. Currently, the VNUS ClosureRFS stylet is the only device specifically cleared by FDA for endovenous ablation of perforator veins.[21]

It should be pointed out that the possibility of skin burn during the procedure is very small, because the large volumes (500 cc) of dilute Lidocaine (0.1%) tumescent anesthesia injected along the entire vein prior to the application of radiofrequency provide a heat sink that absorbs the heat created by the device. Early studies have shown a high success rate with low rates of complications.[22]

Obstructive sleep apnea

RFA was first studied in obstructive sleep apnea (OSA) in a pig model.[23] RFA has been recognized as a somnoplasty treatment option in selected situations by the American Academy of Otolaryngology[23] but was not endorsed for general use in the American College of Physicians guidelines.[24]

The clinical application of RFA in obstructive sleep apnea is reviewed in that main article, including controversies and potential advantages in selected medical situations. Unlike other electrosurgical devices,[25] RFA allows very specific treatment targeting of the desired tissue with a precise line of demarcation that avoids collateral damage, which is crucial in the head and neck region due to its high density of major nerves and blood vessels. RFA also does not require high temperatures. However, overheating from misapplication of RFA can cause harmful effects such as coagulation on the surface of the electrode, boiling within tissue that can leave "a gaping hole", tears, or even charring.[26]

Pain management

RFA, or rhizotomy, is sometimes used to treat severe chronic pain in the lower (lumbar) back, where radio frequency waves are used to produce heat on specifically identified nerves surrounding the facet joints on either side of the lumbar spine. By generating heat around the nerve, the nerve gets ablated thus destroying its ability to transmit signals to the brain. The nerves to be ablated are identified through injections of local anesthesia (such as lidocaine) prior to the RFA procedure. If the local anesthesia injections provide temporary pain relief, then RFA is performed on the nerve(s) that responded well to the injections. RFA is a minimally invasive procedure which can usually be done in day-surgery clinics, going home shortly after completion of the procedure. The patient is awake during the procedure, so risks associated with general anesthesia are avoided. An intravenous line may be inserted so that mild sedatives can be administered. The major drawback for this procedure is that nerves regenerate over time, so the pain relief achieved lasts for only a short duration (6–24 months) in most patients.[citation needed]

Barrett's esophagus

Radiofrequency ablation has been shown to be a safe and effective treatment for Barrett's esophagus. The balloon-based radiofrequency procedure was invented by Robert A. Ganz, Roger Stern and Brian Zelickson in 1999 (System and Method for Treating Abnormal Tissue in the Human Esophagus). While the patient is sedated, a catheter is inserted into the esophagus and radiofrequency energy is delivered to the diseased tissue. This outpatient procedure typically lasts from fifteen to thirty minutes. Two months after the procedure, the physician performs an upper endoscopic examination to assess the esophagus for residual Barrett's esophagus. If any Barrett's esophagus is found, the disease can be treated with a focal RFA device. Between 80-90% or greater of patients in numerous clinical trials have shown complete eradication of Barrett's esophagus in approximately two to three treatments with a favorable safety profile. The treatment of Barrett's esophagus by RFA is durable for up to 5 years.[27][28][29][30][31]

Other uses

RFA is also used in radiofrequency lesioning, for vein closure in areas where intrusive surgery is contraindicated by trauma, and in liver resection to control bleeding (hemostasis) and facilitate the transection process.

This process has also been used with success to treat TRAP sequence in multiple gestation pregnancies. This is becoming the leading method of treatment with a higher success rate for saving the 'pump' twin in recent studies than previous methods including laser photocoagulation. Due to the rarity of this complication, its correct diagnosis statistics are not yet reliable.

RFA is being investigated to treat uterine fibroids. A system developed by Halt Medical Inc. uses the heat energy of radio frequency waves to ablate the fibroid tissue. The device obtained FDA approval in 2012.[32][33] The device is inserted via a laparoscopic probe and guided inside the fibroid tissue using an ultrasound probe (see video demonstration [2]).

RFA is also used in the treatment of Morton's neuroma[34] where the outcome appears to be more reliable than alcohol injections.[35]

See also

References

  1. Gurdezi S, White T, Ramesh P (2013). "Alcohol injection for Morton's neuroma: a five-year follow-up". Foot Ankle Int. 34: 1064–7. doi:10.1177/1071100713489555. PMID 23669161.

 

Therapeutic intervention: 

Trans Arterial Chemo Embolization(TACE)

field_vote: 
  1. Transcatheter arterial chemoembolization

    From Wikipedia, the free encyclopedia

    Transcatheter arterial chemoembolization (also called transarterial chemoembolization or TACE) is a minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply. Small embolic particles coated with chemotherapeutic drugs are injected selectively through a catheter into an artery directly supplying the tumor. These particles both block the blood supply and induce cytotoxicity, attacking the tumor in several ways.

    The radiotherapeutic analogue (combining radiotherapy with embolization) is called radioembolization or selective internal radiation therapy (SIRT).

    Contents

    Principles

    TACE derives its beneficial effect by two primary mechanisms.[1] Most tumors within the liver are supplied by the proper hepatic artery, so arterial embolization preferentially interrupts the tumor's blood supply and stalls growth until neovascularization. Secondly, focused administration of chemotherapy allows for delivery of a higher dose to the tissue while simultaneously reducing systemic exposure, which is typically the dose limiting factor. This effect is potentiated by the fact that the chemotherapeutic drug is not washed out from the tumor vascular bed by blood flow after embolization. Effectively, this results in a higher concentration of drug to be in contact with the tumor for a longer period of time.[2]

    Park et al. conceptualized carcinogenesis of HCC as a multistep process involving parenchymal arterialization, sinusoidal capillarization, and development of unpaired arteries (a vital component of tumor angiogenesis). All these events lead to a gradual shift in tumor blood supply from portal to arterial circulation. This concept has been validated using dynamic imaging modalities by various investigators. Sigurdson et al. demonstrated that when an agent was infused via the hepatic artery, intratumoral concentrations were ten times greater compared to when agents were administered through the portal vein. Hence, arterial treatment targets the tumor while normal liver is relatively spared. Embolization induces ischemic necrosis of tumor causing a failure of the transmembrane pump, resulting in a greater absorption of agents by the tumor cells. Tissue concentration of agents within the tumor is greater than 40 times that of the surrounding normal liver.

    Therapeutic applications

    Transcatheter arterial chemoembolization has most widely been applied to hepatocellular carcinoma (HCC) for patients who are not eligible for surgery.[3] TACE has been shown to increase survival in patients with intermediate HCC by BCLC criteria. It has also been used as an alternative to surgery for resectable early stage HCC and in patients with regional recurrence of the tumor after previous resection. TACE may also be used to downstage HCC in patients who exceed the Milan criteria for liver transplantation. Other treated malignancies include neuroendocrine tumors, ocular melanoma, cholangiocarcinoma, and sarcoma. Transcatheter arterial chemoembolization plays a palliative role in patients with metastatic colon carcinoma. There is a possible benefit for liver-dominant metastases from other primary malignancies.

    Procedure

    TACE is an interventional radiology procedure performed in the angiography suite. The procedure involves gaining percutaneous transarterial access by the Seldinger technique to the hepatic artery with an arterial sheath, usually by puncturing the common femoral artery in the right groin and passing a catheter guided by a wire through the abdominal aorta, through the celiac trunk and common hepatic artery, and finally into the branch of the proper hepatic artery supplying the tumor. The interventional radiologist then performs a selective angiogram of the celiac trunk and possibly the superior mesenteric artery to identify the branches of the hepatic artery supplying the tumor(s) and threads smaller, more selective catheters into these branches. This is done to maximize the amount of the chemotherapeutic dose that is directed to the tumor and minimize the amount of the chemotherapeutic agent that could damage the normal liver tissue.

    When a blood vessel supplying tumor has been selected, alternating aliquots of the chemotherapy dose and of embolic particles, or particles containing the chemotherapy agent, are injected through the catheter. The total chemotherapeutic dose may be given in one vessel's distribution, or it may be divided among several vessels supplying the tumors.

    The physician removes the catheter and access sheath, applying pressure to the entry site to prevent bleeding. The patient must lie stationary for several hours after the procedure to allow the punctured artery to heal. The patient will often be kept overnight for observation and will likely be discharged the following day. The procedure is normally followed up with a CT scan several weeks later to check the response of the tumor to the procedure.

    Agents

    Lipiodol – mixed with chemotherapeutic agents (Lipiodol is nonocclusive, combined with Gelfoam, Ivalon, or other particles)

    Drug eluting particles – slow, sustained release of loaded drug locally with embolic effect leading to tumor ischemia

    - Polyvinyl alcohol microspheres - loaded with doxorubicin

    - Superabsorbent polymer microspheres - loaded with doxorubicin

    - Gelatin microspheres – loaded with cisplatin

    EmboCept S – Degradable Starch Microspheres (DSM TACE)

    Adverse effects

    As with any interventional procedure, there is a small risk of hemorrhage and/or damage to blood vessels. Pseudoaneurysm can develop at the site of puncture in the femoral artery. During this procedure contrast media is utilized, to which patients may develop an allergic reaction. Symptomatic hypothyroidism may result from the high retained iodine load of the contrast. Off-target delivery of embolic agents such as reflux into healthy surrounding tissue is a potential side effect that may cause complications such as ulceration of the gut or cholecystitis. Specialized techniques and devices may decrease the risk. TACE induces tumor necrosis in more than 50% of patients; the resulting necrosis releases cytokines and other inflammatory mediators into the bloodstream. A self-limiting postembolization syndrome of pain, fever, and malaise may occur due to hepatocyte and tumor necrosis.[4] Transaminases may elevate 100-fold, and a leukemoid reaction is not uncommon.

    Intrahepatic abscess (treated by percutaneous drainage) and gallbladder ischemia are extremely rare. Rising bilirubin is a warning sign of irreversible hepatic necrosis, generally occurring in the setting of cirrhosis. In an effort to reduce the likelihood of significant hepatic toxicity, chemoembolization should be restricted to a single lobe or major branch of the hepatic artery at one time. The patient may be brought back after 1 month, once toxicities and abnormal chemistries have resolved, to complete the procedure in the opposite lobe. Retreatment of new lesions may be necessary, if patients fulfill the original eligibility criteria.

    History

    In 1972, surgical ligation of the hepatic artery was first used to treat recurrent hepatic tumors followed by infusion of 5-fluorouracil into the portal vein. Due to the liver's dual blood supply from the hepatic artery and portal vein, interruption of the flow through the hepatic artery was demonstrated to be safe in patients. Tumor embolization eventually developed, blocking the vascular supply to a tumor by primarily endovascular approaches. The application of angiography with embolization followed, and the administration of chemotherapeutic agents with embolic particles evolved into transcatheter arterial chemoembolization.[5]

    References

  2. Miraglia R, Pietrosi G, Maruzzelli L, et al. (2007). "Efficacy of transcatheter embolization/chemoembolization (TAE/TACE) for the treatment of single hepatocellular carcinoma". World J Gastroenterol. 13 (21): 2952–5. doi:10.3748/wjg.v13.i21.2952.
  3. Rammohan A, Sathyanesan J, Ramaswami S, et al. (2012). "Embolization of liver tumors: Past, present and future". World J Radiol. 4 (9): 405–12. doi:10.4329/wjr.v4.i9.405. PMC 3460228Freely accessible. PMID 23024842.
  4. Brown DB, Geschwind JF, Soulen MC, Millward SF, Sacks D (2006). "Society of Interventional Radiology position statement on chemoembolization of hepatic malignancies". J Vasc Interv Radiol. 17 (2): 217–23. doi:10.1097/01.rvi.0000196277.76812.a3.
  5. Stuart K (2003). "Chemoembolization in the management of liver tumors". Oncologist. 8 (5): 425–37. doi:10.1634/theoncologist.8-5-425.
  6. Guan YS, He Q, Wang MQ (2012). "Transcatheter arterial chemoembolization: history for more than 30 years". ISRN Gastroenterol.
Therapeutic intervention: