Hope For Cancer

As we explained above, the main limitation to giving higher dose chemotherapy or moderate dose Total Body Irradiation to kill cancer is Bone Marrow Suppression. Patients who get chemotherapy often have a significant LOWERING of their blood counts; the lowest counts (called the “nadir” ) are usually about 18 days after each “cycle” is given. Then we (hopefully) expect a brisk recovery over the next 7 days, so that by 30 days after administration of a chemotherapy cycle blood counts should return to [near] normal. This is why conventional chemotherapy is usually given in cycles ONE MONTH apart, to allow for Bone Marrow Recovery. Sometimes, the marrow does not recover well, and this explains why oncologists are so adamant about getting a “Complete Blood Count” (“CBC”) prior to giving more chemotherapy. We are particularly interested in whether the Red Blood Cell count is at least 10.0 grams of hemoglobin per deciliter, the Platelet Count is above 100,000 and the “Absolute Neutrophil Count” or “ANC”– (a type of White Blood Cell) is over 1,000. If not, further chemotherapy will commonly be suspended until the “counts”recover. While the fast majority of patients will have a complete bone marrow recovery with conventional doses of modern chemotherapy, some will have a “delayed recovery” lasting month or even years– a consequence of killing some Stem Cells in the marrow. Very rarely, some patients will apparently have all their Stem Cells killed and go on to total “aplasia” — no new blood cells being formed whatsover. This will obviously be fatal if the bone marrow cannot be replaced (“reconstituted”) using someone else’s(“donor”) bone marrow.

It became apparent, in the 1970′s, that we could give more chemotherapy, and possibly cure the patient, if only we could get around the problem of bone marrow damage. We could also give higher doses of radiation to the whole body– about twice as much (12 Gray versus 5 Gray) if we could replace the bone marrow. It had been known for about 20 years that some patients could survive bone marrow failure from other causes (i.e. a drug side effect or virus) if they got a “Transplant” with another person’s healthy marrow. However, in the early studies, most patients did NOT do well getting someone else’s marrow (unless they were an identical twin) since it did not match the marrow they had lost . As transplant of other organs (i.e. kidneys, livers) developed, new drugs became available to “dampen” the immune response against them, called“rejection” . This re-awoke interest in being able to give a cancer patient very“high dose chemotherapy” — enough to actually kill their cancer, but also enough to kill all their Stem Cells. If the patient’s destroyed (“ablated”) marrow could be replaced by someone else’s after the chemotherapy, it might take(“engraft”) and re-establish new blood cell formation. This was especially appropriate for cancers in which we really wanted to destroy the patient’s native marrow anyway– that is when it was contaminated with cancer cells! Thus the first attempts with “High Dose Chemotherapy Followed by Bone Marrow Transplant for Rescue” were done on patients with leukemias, lymphomas and myelomas which dwelt in the bone marrow. Although some patients were cured (~20%) in the 1970′s and 80′s, the main problem for getting higher cure rates and extending the use of Bone Marrow Transplant to other cancers was two-fold. The first problems was that some cancer cells might persist in the body even after high dose chemotherapy– especially for cancers that had already been exposed to chemotherapy and developed a resistance to it. The second was a problem of“rejecting” the transplant, called “Graft Versus Host” (“GVH”) Disease . This was a unique form of rejection, since the patient’s native immune system had been destroyed by ablating their bone marrow. Instead of their body rejecting the transplanted bone marrow, in Graft Versus Host Disease THE NEW MARROW REJECTS THE BODY IT WAS TRANSPLANTED INTO! Every cell in the body has particular protein markers(“antigens”) on its surface to identify it as a member of that unique body, and not someone else’s body or an animal or vegetable. This is what normally stimulates to immune system to recognize and destroy foreign tissue. With Bone Marrow Transplant from another Donor, the patient’s native immune system is dead– they have lost “immunocompetence” . Instead, the immune capability resides in the Transplanted Marrow, which identifies THE BODY as foreign and seeks to destroy it. As will be discussed, newer drugs to“immunosuppress” the transplanted marrow can usually alleviate Graft Versus Host Disease, and allow patients who would previously have died of it to survive.

Besides giving higher doses of chemotherapy, we could also give higher doses of “systemic” (whole body)radiation if we could get around the“dose limiting toxicity” — that is bone marrow destruction. With particular cancers (i.e. lymphoma, myeloma) some cancer cells often will spread to areas where there is poor blood supply or protective membranes exclude chemotherapy. These areas (i.e. brain, spinal cord, skin, testicles) are called “sanctuary sites” . Putting enough drug into the bloodstream to properly diffuse into these sanctuary sites would cause other serious toxicities (i.e. to lung, liver and heart) which still limit the amount of chemotherapy that can be safely given– even with a Bone Marrow Transplant. Gamma Radiation(“photons”) of high energy (i.e. over 10 Megavolts) travels right through the body, killing cancer cells in all the sanctuary sites. Thus, givingTotal Body Irradiation (“TBI”) complements high dose chemotherapy; both kill cancer cells and destroy the bone marrow (which may itself be infested with cancer). If we successfully replace the Bone Marrow Stem Cells, and they start growing (“engraft”) on the bony spicules inside the marrow cavities of bone, they will produce new blood cells. We will then have been able to give higher doses of cancer cell killing(“cytotoxic”) therapy– and have a better chance at curing the patient . Importantly, to “Transplant” Bone Marrow or the Stem Cells which reconsitute it, we DO NOT NEED TO STICK THE NEW MARROW INTO THE PATIENT’s (recipient’s) BONES. Instead, we need only inject it into an an arm vein and the Stem Cells WILL FIND THEIR OWN WAY BACK INTO THE BONES TO RE-ESTABLISH THEMSELVES . Thus “High Dose Chemotherapy” (and possibly Total Body Irradiation ) followed by a “rescue” with“Bone Marrow Transplant” has become the“Latest Effective Therapy” to cure a variety of cancers.

This is just an excerpt from our Complete Cancer Treatment Transcript. Much more, including latest treatments, can be sent to you by email when you order the complete transcript at a nominal cost.

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.

This is just an excerpt from our Complete Cancer Treatment Transcript. Much more, including latest treatments, can be sent to you by email when you order the complete transcript at a nominal cost.