A bill that will provide a one-year extension to the Medicare physician payment rates was passed by the Senate late Wednesday, December 8th and by the House on Thursday, December 9th.  The bill effectively blocks a 25 percent decrease in payments from taking effect on January 1, 2011.

     The measure was introduced in the Senate by Finance Committee Chairman Max Baucus (D-MT) and ranking member Charles Grassley (R-IA) after an agreement was reached with Majority Leader Harry Reid (D-NV) and Minority Leader Mitch McConnell (R-KY).  Senators Reid and McConnell had vowed to develop a plan for a one-year fix and introduce it before the end of the term.

     The bill will be paid for by recouping money from a fund set up in the Health Care Reform Act to provide subsidies to help individuals purchase health insurance through the state benefit exchanges. The measure will also extend some expiring Medicare payment provisions including a cap on therapy services, hospital geographic reclassifications, and the Transitional Medical Assistance program.

     President Obama released a statement recently, calling the measure "an important step forward to stabilize Medicare," but called for a permanent solution from Congress in the next year.

Background

      The lymph system is an important part of the body's immunological defenses. Lymph fluid drains from tissues to lymph nodes where white blood cells mount a defense against harmful cells.  Sentinel Lymph Node (SLN)

      The sentinel lymph node is the first node or nodes which are reached by the lymphatic drainage of the cancerous tissue. Cancerous cells often metastasize to other regions via the lymph. If the sentinel node(s) is found to be cancer free, then there is a <1% chance that the cancer has metastasized, and generally, further node removal is not necessary.

Lymphatic Mapping

      Lymphatic mapping  uses blue dye, radiolabeled colloid, or both, to identify the drainage pattern of the area of interest, generally with the intent of identifying the SLN(s).

Clinical Utility

Advantages

    SLN identification is being studied in a variety of cancers, but it is mainly used in patients with breast cancer or melanoma. One of the biggest advantages of SLN mapping, and subsequent node biopsy, in breast cancer is that when the sentinel node is negative for metastases, patients can avoid a full axillary node dissection (ALND).

    ALND is considered a gold standard for determining the extent of metastases to the lymph nodes. In an ALND, ten to twenty lymph nodes are removed and examined. The surgery is relatively extensive and can lead to complications such as lymphedema. These potential complications and the cost of the surgery may be avoided if the sentinel node is cancer free.

     In addition, since the pathologist only needs to focus on one  or a few nodes, the chance of identifying micro-mestatases in those nodes is higher.

Disadvantages

     This procedure should not be used in breast cancer patients who have already receieved radiation or surgery, as their lymph drainage pattern from the tumor may have been altered.

Radiopharmaceuticals

Agent of Choice

The preferred agent in the U.S. for lymphoscintigraphy is Technetium-99m Sulfur Colloid. The product is prepared using aseptic technique in a room that is

compliant with the regulations of USP 797.

    The colloid should be filtered  by a 0.22 micron filter to reduce the number of large (>100nm) particles. Large particles are removed because they remain at the

injection site, making useful images difficult to obtain.

     In addition, the technetium is useful because it has a  short half-life of 6.02 hours and emits gamma radiation. Past  radionuclides used in lymphoscintigraphy, such as Au- 198, release the more dangerous beta radiation, and their longer half-lives gave the patient an unnecessarily high radiation dose.  Filtered Tc-99m  SC  fits the physical and nuclear needs of patients.

Procedure

Methods vary from site to site

Patient Preparation        

The procedure should be explained to the patient. To reduce the experience of pain, some facilities give the patient an injection of 1% lidocaine or request it be added to the sulfur colloid before the procedure. A cobalt-57 transmission scan is used to obtain an outline of the patients body.

Dose 

Breast: Range of 0.4-2  mCi usually in less than 0.5 ml total volume       

Melanoma: Range of 0.4-1 mCi usually in less than 0.5 ml total volume

 Injection

Four 1 ml TB syringes with 25g needle are commonly used for the injections. The injections should be given in 12-3-6-9  position around the cancerous region. In breast cancer, an injection directly into the mass may also be given.

Imaging

Images are gathered using  a gamma or SPECT camera. Image acquisition should begin as soon as possible after the injections. Sentinel node identification can take between five minutes to one hour.

    Bone pain associated with cancer can be very detrimental to a patient's quality of life.  In addition to debilitating pain, the patient may experience decreased mobility, pathologic fractures, and hypercalcemia.  During this time in the patient's life, palliative efforts become essential to relieve unnecessary suffering.           Treatment of bone pain usually begins with a non-steroidal anti-inflammatory agent.  The use of a NSAID for extended periods of time should be supervised by a physician due to the increased risk of gastrointestinal ulceration and cardiovascular events.  Usually, the analgesic effects of NSAID's do not adequately treat pain as the disease progresses; therefore, physicians switch to opioid analgesics.  As pain increases, larger doses of opioids are required to treat pain, leading to increased side effects such as drowsiness and constipation. 

     External beam field radiation is a commonly used procedure to treat painful metastatic bone lesions.  Although the procedure is effective, only a few sites can be targeted per session.  Bone metastases usually involve multiple sites, so it is often necessary to have the patient return to the hospital for additional treatment.  In addition, cancerous regions of the bone that are not symptomatic are usually not targeted;  therefore, pain may soon develop in these areas. 

     An estimated 50% of patients still have substantial bone pain after standard palliative treatments have exhausted. 

     Irradiating metastases with radiopharmaceuticals offers a few distinct advantages over external beam field radiation.  Treatment with a radionuclide such as Strontium-89 Chloride (Sr-89) or Samarium SM 153 Lexidronam (Quadramet®)  targets multiple sites of metastases with just one injection, including sites that are not symptomatic.  In addition, radiopharmaceuticals do a minimal amount of damage to surrounding soft tissues compared to external radiation.  The degree of palliation by the radionuclides is similar to beam field radiation, and can significantly reduce opioid use.  Approximately 65% to 80% of patients respond to therapy, and the degree of pain relief ranges from 60% to 80%.  Another advantage of these radionuclides is their long lasting pain relief, which on average last 3 to 6 months.  One of the disadvantages of the bone seeking radiopharmaceuticals is the length of time required until pain relief occurs.  For Sr-89 pain relief occurs 7-20 days after the injection, while Quadramet® has maximum pain relief  around 3-4 weeks.  The main side effect of these agents is bone marrow toxicity.  Quadramet® has been associated with more transient and milder bone marrow suppression than Sr-89.  Although the initial dose of Quadramet® is approximately twenty times higher than Sr-89, the more transient bone marrow suppression is likely due to Quadramet®'s shorter half-life of 46.3 hours.  Use of these agents concurrently with chemotherapy or external beam field radiation should be done cautiously due to the risk of severe bone marrow toxicity.

    In conclusion, radionuclides are currently underutilized due to perceived expense and sub-optimal efficacy.  Studies have shown that if radionuclides are utilized early in bone metastases, and are used in place of opioids, patients can save approximately $6,725 per year.  In addition, radionuclides may significantly slow the rate at which bone metastases progress.

     Nuclear medicine physicians should attempt to find those patients for whom treatment is appropriate and utilize radionuclide therapy earlier in the disease's progression.  

-- Kurt Dodson, PharmD Candidate

Dr. Christine Teal, Chief of Breast Surgery, and others of The George Washington University Medical Center in Washington, D.C., determined that Breast-Specific Gamma Imaging/Molecular Breast Imaging (BSGI/MBI) is accurate in establishing tumor size within 5 mm in patients with breast cancer.  The data from the retrospective study demonstrated that BSGI was superior to that of other imaging techniques examined in previous studies, including physical exam, mammography, ultrasound, MRI, and Positron Emission Tomography.  The study results were presented recently at the American Society of Clinical Oncology Breast Cancer Symposium in Washington, D.C.

     BSGI/MBI is a molecular breast-imaging technique that is used to identify early stage cancers by means of a high-resolution, small field-of-view gamma camera and a radiotracer, usually sestamibi.  Cells with increased metabolic activity, such as rapidly dividing cancers, preferentially absorb sestamibi and are viewed as dark spots on the BSGI image.  BSGI is a diagnostic complement to mammography, and is especially helpful for patients that are high risk, have dense breasts, or questionable mammograms.

     One of the main advantages of this technique is that it allows the physician to use imaging techniques to monitor how effective prescribed chemotherapy is in treating the cancer.  This study was performed with the Dilon 6800® Gamma Camera optimized for breast imaging.

     The study included 15 consecutive patients that had BSGI before and after neo-adjuvant chemotherapy.  BSGI was determined to accurately reflect pathologic tumor size within 5 mm after neo-adjuvant chemotherapy in patients with breast cancer.  Dr. Teal noted that BSGI was less reliable in detecting residual microscopic disease in these patients, but that BSGI proved to be a valuable tool for determining patient response to neo-adjuvant chemotherapy.

----PRNewswire

The average person in the United States receives about 360 mrem of whole body radiation exposure each year;  mostly from natural sources of radiation such as radon and the sun.  Radiation workers receive on average an additional 300 mrem of occupation exposure from doing their jobs.

     At radiation exposure levels encountered on the job, the damage potential from radiation results primarily from ionizations of molecules within the body.  These ionized molecules may initiate a chain of events that results in cell damage or death.

     At low doses, such as from every day background radiation, cells are able to repair damage as it occurs.  However, with larger doses delivered over short periods of time (ex. >50 rem/hr), cells may be unable to repair the damage completely and may either be changed permanently (mutate) or die.  Cells that die do not result in permanent damage because the body can replace them.  However, cells that mutate may pass along the mutation to other cells as they divide, go on to produce abnormal cells when they divide.  In the right circumstance, these cells may become cancerous.  This is the origin of our increased risk in cancer, as a result of radiation exposure.

     At high acute doses (ex. > 100 rem/hr) to the whole body, cells die and tissues and organs may fail to function.  This condition is commonly referred to a s "radiation sickness."  Damage to the intestinal lining causes nausea, diarrhea and general weakness.

     With high whole body doses (>300 rem), the body's immune system is damaged and becomes unable to fight off infection and disease.  At whole body doses exceeding 400 rem, about 50% of people die, usually from infection, within 60 days.  At doses in excess of 1,000 rem, massive vascular damage occurs and 0% survive.

     The scenarios above result from radiation doses to the "whole body".  If the exposure is limited to just a portion of the body (ex. Hands, arms), higher doses are tolerated without damage.  But, when talking about the biological effects from radiation exposure, we are usually referring to the whole body.

     Estimates of damage from radiation are made from the results of animal experiments and observations of persons exposed from massive industrial accidents and atomic bombs. It should be kept in mind that very few people have ever received doses of more than 200 rem.  Workplaces are required to utilize safety precautions and procedures to limit any worker's radiation exposure to no more than 5 rem within any one year.  Radiation risk estimates, therefore, are based on the increased rates of cancer, not on death directly from the radiation.

     Risk estimates for radiation were first evaluated by scientific committees starting in the 1950s. The Biological Effects of Ionizing Radiation Committee V (BEIR V) represents the most recent committee and, similar to previous committees, is charged with estimating the risk associated with radiation exposure.  BEIR V focused primarily on external radiation exposure data. 

     It is difficult to estimate risks from radiation, because most of the radiation exposures that humans receive are very close to background levels. In most cases, the effects from radiation are not distinguishable from normal levels of those same effects. With the beginning of radiation use in the early part of the century, the early researchers and users of radiation were not as careful as we are today though. The information from medical uses and from the survivors of the atomic bombs in Japan, have given us most of what we know about radiation and its effects on humans. Risk estimates have their limitations,

1.    The doses from which risk estimates are derived were much higher than the regulated dose levels of today;

2.    The dose rates were much higher than normally received;

The actual doses received by these groups were estimated and are not known precisely.

     According to the BEIR V, the risk of cancer death is 0.08% per rem for doses received rapidly (acute) and might be 0.04% per rem or lower for doses received over a long period of time (chronic). These risk estimates are an average for all ages, males and females, and all forms of cancer. There is a great deal of uncertainty associated with the estimate.

     Risk from radiation exposure has been estimated by other scientific groups and, as expected, there are slight differences in risk estimates due to differing methods of risk and assumptions. 

What is the real risk, in terms of life expectancy, regarding radiation exposure?

     To help answer that question, there are a number of things to consider.  The current death rate for cancer in the United States is approximately 20 percent.  Radiation induced cancers are indistinguishable from cancers caused by genetic, environmental or lifestyle factors.

Based on the previously mentioned risk factors, if a group of 10,000 people were exposed to one rem (whole body exposure), there would be an expectant four to eight deaths (0.04-0.08%*10,000* 1 rem) depending on the nature of the exposure (acute/chronic) in addition to the 2,000 people expected to die from cancer naturally, which would result in a total of 2,004-2008 deaths. 

     Risks can be looked at in many ways; here are a few ways to help visualize risk.

     One way often used is to look at the number of "days lost" out of a population due to early death from separate causes, then dividing those days lost between the population to get an "Average Life expectancy lost" due to those causes.

The following is a table of life expectancy lost for several causes:

You can also use the same approach to looking at risks on the job:

These are estimates taken from the NRC Draft guide DG-8012 and were adapted from B.L Cohen and I.S. Lee, "Catalogue of Risks Extended and Updates", Health Physics, Vol. 61, September 1991

So, in summary, we must balance the risks with the benefit. It is something we do often. We want to go somewhere in a hurry; we accept the risks of driving for that benefit. We want to eat fat foods; we accept the risks of heart disease. Radiation is another risk which we must balance with the benefit. The benefit is that we can have a source of power, or we can do scientific research, or receive medical treatments. The risks are a small increase in cancer. Risk comparisons show that radiation is a small risk, when compared to risks we take every day. We have studied radiation for nearly 100 years now. It is not a mysterious source of disease, but a well-understood phenomenon, better understood than almost any other cancer causing agent to which we are exposed.

Newly Approved Guidelines for Radiopharmaceutical Doses for Children

Washington, DC - The Society of Nuclear Medicine (SNM) and the Society for Pediatric Radiology's Board of Directors recently approved new North American Guidelines for Radiopharmaceutical Doses for Children. These societies have expanded their pediatric radiation protection initiative by standardizing doses (based on body weight) for 11 nuclear medicine procedures commonly performed in children. The Alliance for Radiation Safety in Pediatric Imaging has collaborated in this effort, and will support efforts to promote the new, lower radiopharmaceutical doses.

This information is intended as a guideline only.  Local practice may vary depending on patient population, choice of collimater, and the specific requirements of clinical protocols.  Administered activity may be adjusted when appropriate by order of the nuclear medicine practitioner.

     For patients who weigh more than 70 kg, it is recommended that the maximum administered activity not exceed the product of the patient's weight (dg) and the recommended weight-based administered activity.  Some practitioners may choose to set a fixed maximum administered activity equal to 70 times the recommended weight-based administered activity, for example, approximately 370 MBq (10 mCi) for 18F body imaging.  The administered activities assume use of a low energy high resolution collimater for 99mTc radiopharmaceuticals and a medium energy collimater for I123-MIBG.

     Individual practitioners may use lower administered activities if their equipment or software permit them to do so.  High administered activities may be required in selected patients.

     No recommended dose is given for 67Ga-citrate should be used very infrequently and only in low doses.

1Lassman M. Chiesa C, Flux G, Bardies M.  The new EANM pediatric dosage card.  Eur J Nucl Med Mol Imaging. 2007; 34:796-8.  Additional notes and erratum found in Eur J Nucl Med Mol Imaging.  2008; 35:1666-8 and Eur J Nucl Med Mol Imaging 2008; 35:2141.