Advances for Cancer Patients in Chemotherapy and Radiation, Including Proton Beams and IMRT

Radiation therapy is commonly used in the treatment of cancerous tumors. This technology has been moving toward greater precision in irradiating tumors. Modern x-ray radiation equipment (photon radiation) can focus on and attack tumors while doing less damage to surrounding tissue than previous technologies. State-of-the-art radiation techniques of today involve several different formats. Specific formats have been found to be most effective for specific cancers.

IMRT (Intensity Modulated Radiation Therapy): is a radiation technology that enables the technician to apply narrowly focused radiation directly toward cancerous tumors. IMRT helps to limit the amount of damage to surrounding tissues. The process includes using multiple beams (typically from 7 to 12) aimed at the tumor from various directions. The beams meet at the tumor to administer the desired dosage. Breaking the dose down into multiple beams lessens the level of radiation that healthy tissues are exposed to. The point at which the beams join can be shaped to conform to the exact size, shape and location of the tumor, thus further sparing healthy tissue. Advanced imaging, such as CT, is used to provide precise guidance to the tumor's location.

An important breakthrough in radiation therapy is the ability to provide “respiratory gating,” which enables the radiation equipment to accurately track the radiation target while allowing for the natural body motion caused by breathing in and out. This technology was pioneered by Varian.

An enhancement to IMRT is Varian’s RapidArc VMAT (Volumetric Modulated Arc Therapy). This technology is able to deliver a radiation dose in a 360-degree rotation that is more targeted in much less time than previous units. Treatments that might take five minutes or more with older technologies can be reduced to two minutes.

Image Guided Radiation Therapy (IGRT): takes advantage of sophisticated imaging technologies in order to best target radiation therapy. Prostate cancer is often treated with IGRT. To treat that disease, tiny metal markers are implanted in the prostate using an outpatient procedure. The IGRT equipment is then able to locate the position of the prostate exactly by determining the location of the markers in real time. Varian is a leading manufacturer of IGRT equipment, as is Accuray, Inc., which makes the TomoTherapy system. The technology is similar to IMRT, but better enables radiation technicians to use ultrasound, CT or X-ray images to line up the radiation beam with the intended target.

Brachytherapy: is a method of internal radiation therapy whereby tiny containers of radioactive material, sometimes referred to as “seeds,” are inserted directly in contact with tissue that is afflicted with cancerous tumors. It is a common method of treating prostate cancer and is sometimes used for the treatment of breast, cervical and other cancers.

The latest innovation in this field is called HDR, or high dose rate brachytherapy. In this instance, small radioactive seeds are attached to the end of flexible rods and guided into very specific, imaging-defined locations within the cancerous area. The rods are left in-place for a calculated number of seconds and then removed. This may be repeated a few times over a series of days or weeks. This method exposes the cancer to a very high dose of radiation, and the results have been excellent in many cases. Leaders in this therapy include the UCLA Medical Center, the University of San Francisco Medical Center and Sloan Kettering.

The Gamma Knife is a unique type of radiation therapy with tissue-sparing properties. It involves focusing low-dose gamma radiation on a tumor, while exposing only a small amount of healthy, nearby tissue to radiation. It is often used to treat certain brain cancers.

Patient immobilization is an advancing technology. The point is to hold vital parts of the patient as still as possible so that the radiation beam affects only the desired targets. However, since patients must breathe during treatment, some movement of the body is always going to occur, and this can have an effect on radiation of areas such as the lungs. New technologies enable the radiation beam to allow for and synchronize with a patient’s breathing rhythm.

PBRT, or Proton Beam Radiation Therapy is the use of a highly advanced technology to deliver external beam radiation therapy (EBRT) to a patient in order to kill cancerous cells and shrink tumors. While traditional radiation therapies rely on photons delivered by X-rays or gamma rays, Proton Beam Radiation Therapy relies on a particle accelerator to create and deliver protons. Protons are high-energy particles that carry a charge. By varying the velocity of the particles at the time that they enter the body, physicists are able to control the exact spot within the body where the radiation is released. The higher the velocity, the deeper within the body the radiation begins to take effect.

With traditional radiation (based on photons rather than protons), there is a significant entry dose of radiation that can be harmful to healthy tissues. Proton beam therapy has virtually no entry dose or exit dose, plus the ability to better focus the radiation on the exact place of the tumor, significantly cutting down on side effects and damage to surrounding tissues.

In the U.S., centers are in place at locations including Loma Linda (California) University Medical Center, which is considered a pioneer in applying this technology; Massachusetts General Hospital in Boston, Massachusetts; The University of Florida Proton Therapy Institute in Jacksonville, Florida; the M.D. Anderson Cancer Center in Houston, Texas; and the ProCure Proton Therapy Center in Oklahoma City, Oklahoma. As of mid-2018, there were 28 centers in the U.S., with another 23 centers under construction or planning. PBRT is in wide use or under planning in dozens of locations outside the U.S. including Japan, Germany and Korea. Recent new sites under planning or construction include Argentina, Australia, Singapore, Saudi Arabia and Thailand.

The Loma Linda, California facility began operations in 1990. It was the only hospital-based proton radiation center in the U.S. until 2003. The center has treated nearly 50 different types of cancers.

PBRT may eventually be in very wide use worldwide. Its tissue sparing nature makes it ideal for eliminating side effects and for treating tumors in challenging locations, such as the eye and brain, while it is an extremely popular way to treat prostate cancer. It may be the best possible way to treat small children who have cancer, in order to spare healthy surrounding tissues near the cancer so that young bodies can continue to grow successfully. And, it has potential for the treatment of non-cancerous conditions such as macular degeneration.

Major obstacles facing the development of new proton beam facilities include the immense investment required, the complexity of the accelerator and other equipment, the need to acquire and train specialized staff, and the need to educate referring physicians about this revolutionary technology and its high success rate. The high costs of proton facilities and proton treatments have caused considerable controversy. Many private insurers in the U.S. are refusing to pay higher rates for PBRT than they pay for more standard means of radiation. Eventually, advances in design and technology may make it easier and less costly to establish proton centers. Today’s proton units typically have four treatment rooms.

Newer, smaller and much cheaper proton beam facilities with a single treatment room, and much less adjoining space needed for equipment, are opening, equipped with systems from Mevion Medical Systems, Inc. Its MEVION S250 Proton Therapy System is in use at the S. Lee Kling Center for Proton Therapy at the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis, Missouri. While the older, larger facilities cost between $100 million and $200 million to build, the Mevion system and others like it cost between $25 million and $30 million. Meanwhile, at Loma Linda and elsewhere, highly automated treatment rooms are in use that increase the number of patients that proton centers are able to handle each day, thus amortizing a proton center’s capital cost over a much wider base of patients.

Many insurers stopped covering proton beam treatment for prostate cancer treatment. The newer, less expensive facilities may help those firms to reinstate coverage.

For additional information, see The National Association for Proton Therapy, www.proton-therapy.org. Also, see the web site of Loma Linda University Medical Center’s proton unit, www.protons.com.

Radiation Infusion/PLUVICTO for Prostate Cancer/LUTATHERA for Gut Cancers: For several years, pioneering doctors at premier institutions such as Heidelberg University Medical Center in Germany and Weill School of Medicine at Cornell University in the U.S., as well as health centers in Australia, have been developing techniques in treating advanced prostate and other cancers with a relatively quick, painless injection of radioactive particles. A branded therapy in this regard, called PLUVICTO, was approved by the FDA in 2022 for treatment of prostate cancer, and is manufactured by a unit of drug giant Novartis. PLUVICTO is comprised of two key components: Lutetium-177, a radionuclide, and PSMA-617, a PSMA-targeting ligand. PSMA (prostate specific membrane antigen) is expressed by the majority of cancer cells that are derived from prostate cancer, even when the cancer has migrated to other parts of the body, such as the spine, liver or lymph nodes. Once injected, PSMA-617 speeds through the bloodstream, carrying the radiation along with it. The ligand attaches to cancer cells quickly and efficiently. Then the attached Lutetium-177 emits DNA-breaking radiation within the cells. While patients are often hospitalized for two to three days for observation, the process can also be done on an outpatient basis. Some researchers are also experimenting with Actinium (AC 225) for similar treatments. Meanwhile, the same theory has been utilized to treat certain gastric cancers (GEP-NETs) with good success for several years. A branded drug based on Lutetium for this treatment is LUTATHERA, first approved in the U.S. in 2018 after EU approval in 2017. These therapies offer very significant breakthroughs for patients needing to manage advanced cancers, and similar treatments are likely to emerge for other hard-to-control cancers.

Treating Cancer with Electricity: Another new high-tech tool for treating certain types of cancer is a short burst of electricity directed at the tumor. This process, called electroporation, involves treating the tumor with chemotherapy and then sending short electrical pulses into the tumor with a needle electrode. The electrical pulse allows the tumor to become more porous and thus more susceptible to the chemotherapeutic drugs.

Inovio Biomedical, www.inovio.com, is a leading company in the new field of electroporation therapy. Inovio has clinical trials ongoing for the use of its technology in the treatment of a wide variety of cancers, including breast, head and neck and melanoma.

Radio Frequency Ablation (RFA): RFA is the use of focused radio waves to produce high levels of heat within tumors in order to kill cancer. It is typically applied via needles that have been placed in the tumor, using ultrasound or other imaging techniques to insure correct placement. It is often used in the treatment of cancer of the kidney and has applications in the treatment of tumors found in the lung, liver, bone, breast and adrenal system.

Carbon Ion Therapy: Already in use in Europe and Asia, carbon ion therapy is a relatively new treatment that promises to have a higher relative effectiveness and linear energy transfer than protons or photons when used to destroy malignant cells. The University of Colorado is working to build a $300 million carbon ion therapy center, the first in the U.S. The technology was pioneered in Japan at the National Institute of Radiological Sciences and can be utilized in treating human as well as animal cancers.

High-Intensity Focused Ultrasound (HIFU) is an FDA-approved, minimally invasive procedure typically used for the treatment of prostate cancer. It seeks to destroy malignant cells through the delivery of precisely focused sound waves. Cells are targeted using MRI and confirmed with traditional ultrasound. The sound waves that are aimed at the prostate tissue rapidly increase tissue temperature, hopefully destroying only the cancerous lesions and protecting the healthy surrounding tissue. HIFU system manufacturers include EDAP TMS, Sonacare Medical, Philips Healthcare, Shenzhen Wikkon and Promedica Bioelectronics. HIFU is also utilized in cosmetic procedures to tighten skin tissue.

Improvements in Chemotherapy: Chemotherapy continues to reduce the need for surgical excision of cancers and enable the treatment of cancers that are considered inoperable. Improvements in chemotherapy continue to reduce the number and severity of side effects and the length of treatment, boosting a shift from inpatient to outpatient care. For example, scientists in the Netherlands at the University of Leiden and the University of Utrecht developed new compounds for platinum-based chemotherapy that could alleviate side effects altogether. Although some cancers show resistance to chemotherapy, researchers have recently discovered a unique gene that causes resistance, so compounds may be added to chemotherapy that will block the gene’s ability to resist. In many cases, chemotherapy is combined with radiation, other drugs and/or surgery.

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