What About New Radiation Techniques?
In the past 2 decades, there have been exciting developments in Radiation Therapy based upon both new technology and a better understanding of radiobiology. These developments offer new hope for previously impossible cases, and are helping extend survival from cancer today. A look at these areas is enlightening:
Brachytherapy is useful to give high doses to local areas, while sparing the surrounding tissue. It is often combined with External Beam to succeed in giving a very high dose to the tumor proper, but a more moderate dose to areas peripheral to the tumor (where cancer cells may have escaped to). The larger a tumor, the greater amount of radiation is required to destroy it. Often, for a few clumps of escaped cells outside of the immediate tumor area, a much smaller dose of radiation may be all that’s needed. Brachytherapy in combination with External Beam is standard for cervical and uterine cancer, and may be used alone with early vaginal cancer. It is useful for shrinking tumors of hollow areas, such as the esophagus and airway tubes (“bronchioles”). It is also used on eye tumors (“choroidal melanoma”) as the therapy– instead on removing the eye (“enucleation”). Brachytherapy always used to take at least a day for it’s “application” time, but new High Dose Brachytherapy (“HDR”)
Hyperfractionation– Recall that the dose of radiation given to an area will be limited by the normal tissue tolerance, which varies. Also, that concerning late effects are less if smaller “dose fractions” are used for each treatment. The idea of Hyperfractionation is to give more treatments with a lesser dose for each one, which not only decreases the risk of late effects, but actually allows more total dose to be given (and so a better chance of tumor control). In practice, cancers that have a rapid growth rate get more benefit from hyperfractionation than those with slow growth rates. The patient must come into the Department twice each day (usually 6 hours apart) for treatment, which is inconvenient. However, the increased rate of control for certain cancers (e.g. head and neck cancer) can increased by up to 15% with hyperfractionation, which may make the inconvenience worthwhile. Giving more than once daily treatments with full doses each time is called “accelerated hyperfractionation” and definitely helps control fast growing tumors, but the acute effects can be too uncomfortable to tolerate. The most aggressive protocols (new studies) using radiation now often have an “arm” (portion) of patients getting hyperfractionation, to see how much it helps. Interestingly, brachytherapy is a form of hyperfractionation, since it essentially breaks the treatment into infinitely close together smaller doses.
Hyperthermia– increasing the temperature to the area to get radiated has been shown to increase the effectiveness of radiation cell killing. This is though due to certain proteins in the cells which help protect against radiation, but are inactivated via heating. The temperature needs to be raised about 7 degrees over normal body temperature, which can be done with a heating pad (for skin) or by using microwaves (for deeper tissues). Early studies showed only definite benefit for tumors involving the skin (as advanced breast cancer often does), the main problem with deeper tumors seemed to be inadequate and uneven heating. It has long been known that some cancer patients who got high fevers experienced a remission from disease; new studies are re-examining heating.
IORT (“Intra-Operative Radiation Therapy”)– surgeons can often see tumors when the patient is opened up at operation, and that might be a perfect time to give a focused radiation treatment! New operative suites at Academic Hospitals have an External Beam Machine delivering electrons right in the operating room, so can shine a high dose radiation beam on the tumor proper during surgery. Of course, high doses at one time can lead to greater late effects, and it is not practical to keep opening patients up to give radiation treatments! However, it has been found that one moderately high dose treatment (i.e. 20 Gray) using IORT seems to help survival in many organ cancers without undue late effects. Particular examples are pancreas, liver, and stomach cancer; we are now looking at many surgical cancer situations that may benefit from IORT. 5) Neutrons– and other heavy particles (i.e. helium or metal ions) can be focused into a high radiant energy treatment beam, and obliterate cancers. These are called “high linear energy transfer”(LET) radiation and do not have a dependence upon oxygen that conventional photons have. Several major Universities in the U.S. built machines to give high let radiation to cancer patients, but enthusiasm has declined. The reason is that that slowly dividing normal cells are obliterated by this treatment, and so the Late Effects are much greater. Nonetheless, neutron therapy has achieved success in slowly growing salivary gland and spinal cord tumors, but is still hard to obtain and very expensive.
Stereotactic Radiosurgery– means aiming multiple photon beams at a patient in a single treatment session to destroy a tumor. The risk of late effects is reduced by using these “multiple convergent beams”, since each area of normal tissue that is around the tumor gets only a very small fraction of the dose the tumor gets. To date, stereotactic radiosurgery has been used for brain tumors, since the head can be kept immobile in a “halo”, and no movement is essential for the accuracy of the treatment. The patient comes into the the hospital, has a “halo” (frame) fitted on their head, and gets a CT or MRI scan. They wait in their room, while the neurosurgeon, radiation oncologist and radiation physicist devise a “treatment plan” by using a computer that keeps track of the beams in 3-dimensions. Several areas may be treated in one afternoon. The patient is called, set up in a modified LINAC (or sometimes a specially designed Cobalt-60 unit called a “Gamma Knife”) and the painless treatment is given. The halo is removed, but patients are often kept overnight for observation, and go home the next day. This is a major improvement over having to go through open brain neurosurgery (“craniotomy”) to remove a metastatic brain tumor, or a brain tumor which has relapsed after regular External Beam Treatment. Some facilities routinely use stereotactic radiosurgery as the “boost” after External Beam; it is easier and safer than surgically implanting radioactive rods into the brain to boost External Beam treatment as used to be done. New efforts are underway to utilize stereotactic radiosurgery for other body areas.
Whole Body or Hemibody Radiation– Normally our ability to give radiation to large areas of the body is limited by the normal tissue tolerance. We can often give a small portion of an organ(s) high dose, but will cause total organ failure if we treat the whole thing. Whole body radiation must either be relatively low dose of superficial to avoid excessive damage. In preparation for bone-marrow transplant, a beam of photons may be used (usually in 5 – 6 treatments) to obliterate the existing bone marrow, blood cells, and (hopefully) cancer cells. This is done with a high-energy LINAC, a plexiglass “scatter” screen is put front of the patient to boost skin dose (recall that high energy beams poorly treat skin). This would be lethal (owing to destroying blood forming capacity) if a transplant were not given afterward to reconstitute blood forming ability. However, it shows extremes we can go to for killing cancer cells, so long as we can still save the patient. For certain very widespread leukemias involving on the skin (“mycosis fungoides”) a beam of electrons can be used to treat the whole skin surface to cure disease.
Hemibody Radiation– For patients with advanced cancer involving many areas of bone, quick relief can be gotten by a low dose (i.e. 8 Gray) of radiation aimed at one-half of the body, so called “Hemi-Body” therapy. This is done is a single session and takes only a few minutes of the machine actually being on. It’s main side effects are nausea (which can be controlled with medicines) and lowering of blood counts, but is is normally effective palliation. Wide areas of radiation may succeed in putting chronic lymphoma or leukemia patients into remission, or even possible cure. This is owing to tendency of certain white blood cells to undergo bursting (“apoptosis”) if treated with relatively low dose radiation.
Combination Therapy– means using radiation as one of several “modalities” (i.e. surgery, chemotherapy) when treating cancer. Many new strategies using combination therapy are in current testing, in clinical trials. It makes sense that radiation is a local, or at best regional, therapy– and something else such as hormones or chemotherapy may kill distant cells which have escaped from the main tumor. These cells are often too small to be detected(“micrometastasis”) but we know the are they in some patients who relapse years later in distant areas (such as a breast cancer though cured which reappears in bone a decade later). Radiation may be given prior to, during (IORT) or after surgery, and also scheduled in many ways with chemotherapy. Combination therapy has dramatically raised cure rates for many childhood cancers, and improved the results for adult organ cancers (i.e. stomach, esophagus, pancreas). Although side-effects tend to be greater with combination therapy, the increased cure rates are worth it to many.
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