Mary Jo Update #17 - Derby Week: Chemo Cocktails and "Peeing In The Hat"

We were at the hospital at 7:30am this morning for Mary Jo's first day of chemo before her stem cell transplant on Monday, May 6th. This is called the conditioning phase. We also got the results of Respiratory Viral Panel Test and the PET Scan that were ran yesterday. The result of both was negative which indicates that see has none of the 20 respiratory infections known to man, and that her Mantle Cell Lymphoma is still in remission.

 The chemo cocktails for the next four days are etoposide and cytoxan. The side effects are about the same for both. Other than Cytoxan being the one that causes the loss of hair. Here's a list of the side effects:

Cytoxan Side Effects

Get emergency medical help if you have any of these signs of an allergic reaction while taking cyclophosphamide (the active ingredient contained in Cytoxan) hives; difficjult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• blood in your urine or stools, pain or burning when you urinate;
• pale skin, feeling light-headed, rapid heart rate, trouble concentrating;
• sudden chest pain or discomfort, wheezing, dry cough or hack, feeling short of breath on exertion;
• fever, chills, body aches, flu symptoms, sores in your mouth and throat;
• easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;
• extreme thirst with headache, vomiting, and weakness;
• jaundice (yellowing of the skin or eyes); or
• severe skin reaction -- fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common side effects may include:

• nausea, loss of appetite, stomach pain or upset, diarrhea;
• temporary hair loss;
• a wound that will not heal;
• missed menstrual periods;
• changes in skin color; or
• changes in nails.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

Some of the side effects are controlled by giving the patient other drugs to counteract the effects of the chemo drugs. They will giving Mary Jo about 16 liters of fluids (16 bags) over the next 4 days to protect her kidneys from damage. She spent a lot of time in the bathroom today. It was kind of comical because there two other people who also began their first day of chemo today, too.

Everything going in or out for the next four days must be measured. In the stem cell clinic the nurses keep the measurements on a scoresheet. When we are in the apartment away from the clinic Mary Jo has to do the measuring by writing down the amount every time she drinks something, and writing down how much every time she pees. To accomplish the measuring part, ladies "pee into the hat". The hat could be a Derby hat if you put a brim, some ribbon, flowers and a horse or two on it. Of course, gentlemen pee into a measuring cup.

When you pump this much liquid into a person they can easily become bloated, and it throws off the body's chemistry. The levels of things like sodium and potassium can be affected. It also causes the blood pressure to rise dramatically, so they have to monitor those fluids carefully. If Mary Jo doesn't pee enough, they will give her lasix which is a diuretic which will REALLY makes her pee a lot.

Living in the apartment is great for going to and from the hospital. We just walk across the pedway shown in the picture above. The pedway crosses over 21st Ave. S. to the 5th level of the medical center's Central Garage. There are actually five different parking garages serving the medical center. I found out that those STAT Flight helicopters that I was hearing last night don't land on the parking garage roof. They actually land on the Children's Hospital roof. Here's a video. A pretty impressive helicopter for saving lives.




After the treatment Mary Jo and I walked to a CVS drug store a few blocks from the apartment for a prescription she needed. We cut across part of Vanderbilt's campus which is right next to the apartments. The campus is beautiful nearly every building has large columns in the front. They are getting ready for the commencement activities next week.

Tomorrow more cytoxan, etoposide and "peeing in the hat."



It was a pretty tiring day for My Girl.

Mary Jo Update #16 - The Last Supper

We have made the journey to Nashville, and moved into the Viillage at Vanderbilt apartments right across 21st Ave. S from the Vanderbilt Medical Center.

Mary Jo had blood labs first thing this morning. Then, a Respiratory Virus Panel (RVP) Test which is used to see if the patient has any of the twenty human respiratory viruses. A saline solution is squirted into each nostril. Then, the solution is captured for analysis as it exits the other nostril. After that, we met another one of the transplant doctors named Dr. Madan Jagasia. 

Dr. Jagasia told us that since the transplant was going to be made with less than 2 million stem cells the grafting could take a little longer than normal, and that Mary Jo's platelet levels may take longer to get back to normal. Platelet infusions after the transplant will most likely be necessary.

 He also said that a search would be made of the nationwide donor inventory to try to find a stem cell match for Mary Jo.  In case, a future allogeneic transplant would be needed. After the meeting with Dr. Jagasia, Mary Jo had a PET Scan to establish a baseline for comparison with a post-transplant scan that will be done 100 days after the transplant. 

The day did not go without it's share of difficulties besides the things that Dr. Jagasia told us. But, the hospital staff may have had an excuse today. Someone told us that they were jumping through hoops because of a Medicare/Medicaid audit was being performed by someone, maybe the state. 

 Evidently, no one had ordered the RVP Test. So, it was delayed, and we didn't get the results today. Our  social worker said that it was OK to sign the lease for the apartment without the results since Mary Jo was asymptomatic.

The PET Scan took longer than normal because the hospital sent two patients to Radiology to be worked into an already crowded schedule. I felt sorry for one of the patients. Evidently, he had brain cancer, or something else. He had several incisions in his head, and a tube coming out the top of his head. Mary Jo didn't have any problem letting him go ahead of her. He deserved to be given preferential treatment.

There was a little problem with the apartment when we checked in, too. Evidently, in the confusion a couple of weeks ago when we thought that we were going to be sent home for two weeks to rest, and then return for additional stem cell collection sessions. Our name was removed from the apartment waiting list and not reinstated, as it should have been. After some discussion and checking, to his credit, Carter at the apartment rental office was able to get us into the apartment that we were actually scheduled to move into anyway.

The apartment is pretty nice, and one of the larger one bedroom apartments. We are on the first level. The parking garage is on the ground level. Our building has an elevator. But, it was still a pretty good hike to get all of the stuff that we brought moved from the car into the apartment. At least, Mary Jo was feeling well enough now to help move the stuff in. She probably won't be able to help when it's time to move out.

Nearly all of the people who live in these apartments are Vanderbilt students, except for old people like us, who are here for medical reasons. I think they are celebrating the end of finals. It's not your place to come for a quiet retreat. Graduation  festivities begin next Wednesday, May 8th with commencement on Friday, May 10th. That ought to be fun.

We haven't heard any dogs, trains or fire engines. We have beentreated to a new sound of Nashville. Vanderbilt's STAT Flight helicopter has taken off and landed about three times this evening. It sounded like it was landing on the apartment building roof, but it was actually landing at the hospital helipad on the roof of the parking garage right across the street. Maybe, they are practicing touchdowns.

Nashville's AAA baseball team is named the Nashville Sounds which is appropriate in more ways than one. They play in the Pacific Coast League. I looked it up. Nashville is 2,021.1 miles from Santa Monica Beach.

For dinner tonight, we went back to Jim 'n Nick's BBQ out Charlotte Pike a piece. We had went there a couple of weeks ago when we were here. It's about the best BBQ this side of Mark's, Smokehouse, or Bootleg on Bardstown Road. Since Mary Jo will have her first chemo treatment from 8:30am until 4:30pm tomorrow, she called tonight's meal her "Last Supper". At least, the last decent one for awhile. She will be starting her frozen dinner bacteria free diet tomorrow.

We hope that everyone has a great Derby Week. We will miss being home for the Derby this year. Thanks for all of your thoughts and prayers.

Neutropenic Diet Benefits: Fact or Fiction?

 For a number of years the Neutropenic Diet below has been recommended for patients undergoing chemotherpy and stem cell/bone marrow transplants. However, recent studies question the value of following the diet as strictly as it is written. See the article below. Nearly everyone agrees that fresh vegetables and fruits, fresh juices, and raw eggs should be prohibited from the patient's diet. But, the criteria for dietary restrictions vary widely between hospitals.

Neutropenic Diet by gerrymattingly

The Benefit of the Neutropenic Diet: Fact or Fiction? 

Chemotherapy has had a major impact on the survival rates of patients with cancer, particularly those with hematologic malignancies. Neutropenia due to chemotherapy is the major risk factor for infection [1]. Several studies [2, 3] reported the isolation of gram-negative organisms such as Pseudomonas aeruginosa, Escherichia coli, Klebsiella, and Proteus from a variety of foods, particularly salads, fresh vegetables, and cold meats. Aspergillus, a fungus often lethal to patients with prolonged neutropenia, was found to be isolated from food, water, and ice [4].

The movement of these bacteria from the gastrointestinal tract (GI tract) to other body sites, called bacterial translocation [5], is thought to cause many of the infections in patients with neutropenia. Deitch et al. [6] demonstrated that bacteria in the GI tract can travel through the intestinal mucosa to infect mesenteric lymph nodes and body organs. Bacterial overgrowth, immunosuppression, physical disruption of the gut by chemotherapy or radiotherapy, slowed peristalsis due to narcotics or antidiarrheal agents, trauma, and endotoxins are factors contributing to bacterial translocation [7]. Theoretically, bacterial translocation can be decreased by reducing sources of pathogenic bacteria from food and decreasing the bacterial burden of the gut with oral nonabsorbable antibiotics.

The above studies led to the use of the neutropenic diet. The neutropenic diet is also called a sterile diet, low microbial diet, or a low bacterial diet (LBD). However, a standardized definition of the neutropenic diet has not been established [8, 9]. Variations of the neutropenic diet include an exclusively sterile diet (e.g., all foods that have been made sterile by canning, baking, autoclaving, or irradiation), a LBD (well-cooked foods only), or a modified house diet (i.e., a regular diet omitting fresh fruits and vegetables) [8–11].

The benefit of the neutropenic diet has never been scientifically proven [12]. Despite this, neutropenic diets are used in many institutions. A descriptive telephone survey by Todd et al. [11] looked at the use of LBDs for chemotherapy-induced neutropenia among 21 childrens' hospitals and found that (a) 43% of these hospitals used the neutropenic diet for neutropenic non–bone marrow transplant patients and (b) 86% of these hospitals used the neutropenic diet for bone marrow transplant patients. French et al. [13] surveyed 10 bone marrow transplant centers in Canada and northwestern United States and reported that 5 of the 7 responding hospitals used a neutropenic diet. However, the timing of the start of the diet and the food choices that were allowed varied with each institution. In a national survey, Poe et al. [14] found that 66% of responding transplant units enforced some type of modified microbial diet. Smith and Besser [9] surveyed 400 members of the Association of Community Cancer Centers (ACCC) and reported that 78% of the responding hospitals restricted diets of patients with neutropenia. The most commonly prohibited food items in these institutions were fresh vegetables and fruits, fresh juices, and raw eggs. Criteria for dietary restrictions varied between hospitals. The most common reasons for restricted diets were documentation of neutropenia defined as a white cell count <1,000 mm³ and documentation of risk factors for neutropenia such as recent chemotherapy.

Read entire article here:

Stem Cell Transplantation Video Chat

Access Greg Dafoe's Stem Cell Journals here:

You may also access the link to Greg's journals from the OTHER LYMPHOMA BLOGS AND WEBSITES section of the sidebar

Doctors Protest 'Astronomical' Canser Drug Costs

From Yahoo! Health

With some new, potentially lifesaving cancer drugs costing up to $138,000 a year, about 120 leading cancer specialists have joined forces in an unusual protest aimed at getting pharmaceutical companies to cut prices.

Charging high prices for drugs cancer patients need to survive is like “profiteering” from a natural disaster by jacking up prices for food and other necessities, leading cancer doctors and researchers from around the world contend in a new paper published in Blood, the journal of the American Society of Hematology.

Of 12 new cancer drugs that received FDA approval last year, 11 of them cost in excess of $100,000 a year—prices that the specialists attack as “astronomical,” “unsustainable,” and maybe even immoral. What’s more, only three of these drugs were found to improve patient survival rates and of these, two only increased it by less than two months, according to theWashington Post.

“Advocating for lower drug prices is a necessity to save the lives of patients,” say the specialists who wrote the paper, who specialize in chronic myelogenous leukemia (CML), but emphasize that sky-high drug costs affect patients with many types of cancer.

Going Bankrupt to Stay Alive

“Medical illness and drug prices are the single most frequent cause of personal bankruptcy” in the US, according to the specialists, where patients’ copayments on drug prices average 20 percent of the total cost of the drug. That means that cancer patients often face having to shell out $20,000 to $30,000 a year, simply to stay alive.

The specialists also note that astronomical drug prices may be the single most common reason why patients stop taking lifesaving drugs. This is particularly true for those with CML, which requires daily treatment for long-term survival.

As a result the paper says, “grateful patients may have become the ‘financial victims’ of the treatment success, having to pay the high price annually to stay alive.” One study found that 10 percent of cancer patients fail to fill new prescriptions for oral cancer drugs.

For some patients, such as breast cancer survivor Patti Tyree, medical costs—not the disease—are stealing their future. The 57-year-old postal worker inherited $25,000, but after just one round of treatment for breast cancer, nearly half of the money is gone—and bills continue to pour in, she told USA Today.

One of the more expensive therapies for CML is Gleevec, a cancer drug that generated $4.7 billion in sales last year, making it the bestselling drug for its manufacturer, Novartis. Another Novartis leukemia drug, Tasigna, had sales of $1 billion, according to The New York Times.

Doctors Pressure Drug Companies to Slash Prices

Some of the specialists who joined the protest were inspired by the doctors from Memorial Sloan Kettering Cancer Center (MSKCC) who refused to use a new colon cancer drug called Zaltrap because it cost more than twice as much ($11,063 on average for one month of treatment) as another drug (Avastin) without improving outcomes.

“Soaring spending has presented the medical community with a new obligation. When choosing treatments for a patient, we have to consider the financial strains they may cause alongside the benefits they might deliver,” the MSKCC doctors wrote in an October, 2012 op-ed for The New York Times about their boycott.

Subsequently, the drug’s manufacturer slashed the price by 50 percent.

Cancer Drugs Rank Among the World’s Most Expensive

The idea that "one cannot put a price on a human life” has led to wildly overblown healthcare costs in the U.S., estimated at $2.7 trillion in 2011, according to the paper’s authors, who urge insurers and government to more aggressively negotiate with pharmaceutical companies.

Many reports show that cancer drugs consistently rank as the most expensive therapies, even though some only extend life by a few months or offer no benefit over older, less expensive drugs.

The paper discussed Gleevec, which was originally priced at about $30,000 a year when it was approved in 2001. Since then, the price has tripled. However, its manufacturer told The New York Times that relatively few patients actually pay the full cost—and that the price reflects the high cost of developing new medications, which reportedly exceeds $1 billion.

Yet even doctors involved with developing Gleevec, such as Dr. Brian Druker, are criticizing Novartis, which raked in $4.7 billion in sales for the drug in 2012.

“If you are making $3 billion a year on Gleevec, could you get by with $2 billion?” Dr. Druker, now director of Knight Cancer Institute at Oregon Health and Science University, said in an interview with The New York Times. “When do you cross the line from essential profits to profiteering?”

On This Side Of Cancer

Chemo Treatment Side Effects

From the Non-Hodgkin's Lymphoma Cyberfamily

Side effects from treatment

Side effects are very difficult to predict. Not only is every patient different, but the side effects are largely dependent upon what chemotherapy is being used. 

If you know what regimen you are going to have you can look up the side effects of each drug or the whole protocol at the three links below.

BC Cancer agency patient information sheets

BC Cancer Agency professional cancer drug monographs

BC Cancer Agency chemotherapy protocols

Check out our "Support Drugs" page to read more information about what drugs are used to manage side effects.

There are some chemotherapy regimen's which come with nearly no side effects. Rituxan is a good example of this. Further information about Rituxan side effects is at the bottom of this page.

CHOP is one of the most common chemotherapy regimens used for NHL. It is considered a medium strength combo, and comes with mild to moderate side effects for most people, and severe side effects for some. 

In medical studies side effects are assigned a grade to indicate their severity. Grade 1 are the mildest level of toxicity, and Grade 4 the most severe. Here is link to the World Health Organization definition of what the grade means for each type of side effect. This link should open the PDF document to page 71. if not then see page 71 for the start of the definitions.

World Health Organization definition of toxicity grades

Nausea and vomiting

Let's start off with the nausea and vomiting thing. For the most part that should not be a problem no matter what regimen you are on. The drugs Ondansetron and Granisetron (brand names Zofran and Kytril) are so effective that even with the most powerful chemotherapy most patients experience no vomiting at all. Ondansetron is the more common choice, but Granisetron is also very common. Both drugs are very expensive, but even if you must pay for your own drugs you will not regret the expense. There are other drugs which help as well, but those are the two most potent ones.

Personal note from the webmaster: I didn't take either for my first CHOP chemotherapy and to say that I barfed my guts out was an understatement. I took it every time after that and never so much as had a tummy ache.

There are also several newer anti-nausea drugs which can be used in conjunction with Ondansetron or Granisetron when even stronger anti-nausea measures are needed. They are Dolasetron and Palonesetron. More information about all these drugs is on our Support drugs page. Just click on that menu item on the left.

Mouth sores and changed taste

Mouth sores are not too common with regular chemotherapy but they are very common during Stem Cell Transplants. They are caused by the damage to the mucous membranes of the mouth and throat, and they can be extremely painful. Often morphine is required during an SCT to control the pain.

The first step in avoiding them is to practice good oral hygiene using a mouthwash of baking soda and water. Swish 3 or 4 times a day with that. When brushing be sure to use a soft bristle toothbrush.

One of the most common treatments is an over the counter remedy called Magic Mouthwash. It is something your pharmacist can make up for you as follows:

Magic Mouthwash recipe

Viscous Lidocaine (1 part) 
Maalox (1 part) 
Benadryl (1 part)

Swish and spit 5 ml no more often than every 4 hours. It will help ease the pain and prevent further mouth sores from developing. Nothing but time will totally heal them, but they will heal eventually.

Another preventative measure is an anti-fungal mouthwash of Nystatin. It prevents fungus and yeast infections. Typically you swish and swallow it since it is not absorbed through the stomach or skin.

Taste changes are harder to control. Many people find that meat in particular becomes unpalatable and tastes like ash, or metal. Others find that food in general just has no taste and they lose the enjoyment they had in eating. This as with most side effects is temporary but it can be very disheartening. It is important to keep up proper nutritional intake during chemotherapy so if your taste is changed to the point where you can no longer eat properly you should be sure to supplement your diet with a proper daily vitamin, or supplemental nutritional meal replacement shakes and drinks.

Fatigue

This is one you will probably experience with most chemotherapy and many radiation treatments. It is often the most bothersome side effect because it can last a long time.  It is usually more severe with age, and poor physical fitness, but even being young and fit is no guarantee you will avoid it. One of the keys to managing fatigue is to keep active even when you feel too tired. Fatigue feeds on itself, so keeping active helps keep it under control. Just don't overdo anything. If all you can manage is a walk to the end of the street and back, then that's OK.  For the majority of patients fatigue does go away after treatment stops. Your local Cancer Society or Cancer Centre can provide you with information about how to deal with and combat fatigue.

Hair loss

Yes this probably the most dreaded side effect. For some reason we humans are very attached to our hair and get quite emotional when it is involuntarily taken away from us. Even knowing it will grow back doesn't soothe the soul very much.  The good news is that when it does grow back most people find they have more of it, it is darker, and it is usually curly for about the first 9-12 months after it grows in.

One aspect of hair loss that is seldom mentioned is that it usually affects the whole body. Arms, legs, chest and beards for men, and well, other areas too. Even those pesky nose hairs are likely to go away. Eyebrows and eyelashes seem to be about 50/50 chance.  
Whether or not you lose your hair really does depend on the therapy. Rather than trying to list all the drugs that cause hair loss, we have listed just a few that are UNlikely to cause hair loss:

Rituxan, Zevalin, Bexxar, - No chance of hair loss

CVP - Little chance but some hair thining likely

Fludarabine - Very little chance of hair loss

Chlorambucil - Very little chance of hair loss

Peripheral Neuropathy

This means numbness or tingling in the extremities. This is caused by damage to the nerve endings. Mostly the fingers and toes. This side effect is very particular to certain drugs. Mostly Vincristine and related drugs. With Vincristine PN is very common but it also usually goes away within weeks or months of stopping therapy. When it gets to the point that the patient is dropping things, and can't do simple tasks like buttoning a shirt, then the doctor should reduce or eliminate the dose.

Neutropenia, Thrombocytopenia, and Anaemia

Neutropenia means a lack of the specific white blood cells called Neutrophils. Those are responsible for fighting infections. Thrombocytopenia is the lack of platelets, which are responsible for blood clotting and prevention of bleeding. Anaemia is the lack of red blood cells which deliver oxygen to the body's cells, and therefore a lack of it results in fatigue.

Of the three Neutropenia is the one that is virtually guaranteed for anyone undergoing treatment. All the NHL treatments are geared towards killing white blood cells. What is important is the level of neutropenia. If it becomes severe then any infection no matter how small, can become life threatening. During standard chemotherapy this is not all that common but the risk can't be ignored. Some cancer centres will administer Neupogen during chemotherapy, although that is not considered standard practice.  During an SCT, then Neupogen is considered a "required" therapy. Neupogen is a neutrophil growth factor which stimulates your body to produce them very rapidly.

Thrombocytopenia and Anaemia are less common. Thrombocytopenia is harder to deal with, without using platelet transfusions. Anaemia can be dealt with either with blood transfusions or with red blood cell growth factors like procrit and aranesp. See the "Support Drugs" page for more information on those.

Rituxan side effects

Here we will discuss Rituxan side effects separately from chemotherapy. The notes here are likely to apply to other monoclonal antibody therapies as well since they have much in common with Rituxan.

Rituxan deserves it's own section on side effects because it is not a chemotherapy. It is a monoclonal antibody which targets only Lymphocytes (normal or cancerous) with the CD20 marker on their surface. Therefore it does not damage any other cells so side effects are rare. Nonetheless it is a foreign substance that is being put in your body, and sometimes your own immune system can react to that invasion in unusual ways.

During the first infusion of Rituxan is when most patients will experience some reactions. They will start the drip off very slowly to avoid most of them. These reactions include fever or chills, rigors (shivering uncontrollably), swelling of the mouth or throat, headache or body ache, hypotension (low blood pressure), itching, dizziness and maybe nausea. All patients will be premedicated with Tylenol and Benadryl to minimize these reactions.  It is extremely important for the patient to notify the nurse the instant he/she notices any of these reactions so they can stop the drip and give further medication.

Almost every patient will experience some of those reactions but not all of them. Fevers, chills, rigors and other "allergic type" reactions are most common. There are many other very rare infusion reactions most of which are not serious. Click here to go to the full Rituxan "Adverse Events" web page to read about them.

Once the reactions start, they will stop the drip, give more medication wait a few minutes then start the drip again.  If those reactions are very strong they may also give Demerol and/or steroids when they stop the drip. Once the drip is started again they will increase the rate about every 30 minutes if there are no further reactions.

After that first infusion it is rare to experience any further reactions during the infusion.  However if they do occur they will be treated exactly the same as during the first infusion. 

Later side effects

These are even more rare. Nevertheless some patients do experience additional side effects unrelated to the actual infusion.

The following anecdotal events have been reported by patients following Rituxan therapy. These events were in response to the question, "What unusual side effects have you noticed after Rituxan therapy as opposed to infusion related side effects?"

Remember, these are patient reports and not scientifically verified side effects.

• Body aches and pains lasting many hours after each infusion was done.
• My doctor suggested Rituxan therapy may preclude vaccine treatment until the B-cell population has had a chance to recover. That can take 6-9 months as per Rituxan's own documentation.
• Ongoing allergic type of side effects, runny nose, sneezing, rashes, itching etc.
• Possible itching peeling and blistering of skin on the hands and feet
• Tightness in chest and raspy throat
• Stuffiness or runny nose for days or weeks after the infusion
• Other minor lung irritations
• Some of the above resolved by Benadryl or Steroids like Prednisone.
• Folliculitis of the scalp. (Inflammation of the hair follicules)

Live video chat on the stem cell transplant experience this Friday

From Greg Dafoe, who moderates an NHL Discussion Group. 

Note: I will post the video of the chat with Greg from the Lymphoma Foundation Canada when it becomes available on Youtube. I read that only the first 10 people will be able to join the live video chat at the time below.

The Lymphoma Foundation Canada has asked me to co-host a live Google+
Hangout this Friday (April 26) at 3:00pm Eastern Daylight time to talk
about my SCT experience.

Check your own time zone here
http://www.timeanddate.com/worldclock/

My co-host is Dr. Kelly-Ann Pike

To join the Hangout or to watch just go to the Lymphoma Foundation Canada
website. The link is on their home page and calendar page.

http://www.lymphoma.ca

Greg Dafoe
Hamilton, Ontario
dx 09/98 follicular grade 2, Stage IV
CHOP X 7, Radiation X 20; 09/98-05/99
Auto SCT 04/17/2002 

Lymphoma Foundation Canada Video: Alive Again

Lymphoma and PET Scans

A discussion on the role PET Scans play in the diagnosis of Lymphomas from Non-Hodgkins Lymphoma Cyberfamily

This page is here because there is a lot of confusion about PET scans and their role in lymphoma. It is a common misconception that PET scans are "better" than CT scans or other types of diagnostic imaging. This simply is not true. PET scans are "different" and provide quite different information but they are not better.

CT scans provide a picture of the size, shape and structure of what is inside the body. Because of this level of detail that they provide they are the primary type of scans used for lymphoma.

PET scans provide detailed information about metabolic activity. They are not so good at providing information about size, shape and structure. All they show is what tissues are metabolically active, and the exact location. But like many types of medical tests, they are also subject to false positive or even false negative results.

This page is divided into three sections. The first section discusses what PET scans are, and shows some of the images they produce. The second section deals with what PET scans are good for, and how they are being used. The final section discusses what PET scans are not good at, and their limitations.

Perhaps the best place to start however is the USA National Comprehensive Cancer Network recommendations on the use of PET in cancer.

NCCN Task Force Report: PET/CT Imaging in Cancer (pg 18 for lymphoma)

What is a PET scan

PET scans detect metabolic activity. That means they can see cells that are consuming sugar for energy. PET scans are very good at detecting metabolic activity where it does not belong. The patient is injected with a sugar molecule that has radioactive Fluorine attached. It is 18-Fluorodeoxyglucose or 18-FDG.

In most cases after the injection the patient must lie or sit quietly for about an hour to allow the 18-FDG to distribute about the body. They must remain calm because movement can cause that part of the body to require more energy and absorb more sugar. Even chewing gum will cause a problem.

Next the patient goes into the scanner and the scanner detects where the radiation is accumulated in the body. It does this because the radiation is gamma radiation that is exiting the body and can be detected by the gamma camera (aka PET scanner)

Parts of the body that require a lot of energy will absorb the 18-FDG and therefore show up on the image. There are places that SHOULD show up, like the brain, heart, bladder, kidneys etc. These places are all very active and need energy.  What the radiologist will look for is "abnormal" accumulation in places where it does not belong.

• Click here to see what a PET scan looks like (and a combined CT/PET)

Those who have low-grade or indolent forms of lymphoma will benefit less from the use of PET. The slow growing nature of these types of NHL means that the tumours are not growing quickly and thus are less likely to attract the glucose. While most types of indolent lymphoma will show up to some extent on a PET scan there are some types which will fail entirely to show up. The important point though is that indolent lymphomas are generally only treated when the tumour burden begins to impact the quality of life, or threaten major organs. These conditions are easily detected by the patient (quality of life) or the CT scan (threatening major organs) so the cost of a PET scan can't usually be justified.

Furthermore the PET scan is unlikely to change the treatment course so its value in low-grade lymphomas is limited.   A more recent advance is the combination CT and PET scanner. This machine does both types of scan at the same time, which is far more cost effective. It also allows the radiologist to combine the images for a more detailed view of what is going on. Click the first link above to see combined CT/PET images. The following links will help you understand when and why to use PET scans.

• PET scans in accessing response to treatment 
• PET scans in the staging of Lymphoma 
• Can PET distinguish between indolent and aggressive NHL?

What can PET scans do well

PET scans are good at finding metabolic activity where it does not belong. Lymphoma (and other cancers) often have high metabolic activity since they are growing more rapidly than they should. This means PET scans are good at finding small areas of cancer that don't show up on CT scans. PET is excellent at determining if a mass left over after treatment is just scar tissue or still active cancer.

PET scans done in the middle of treatment for aggressive lymphomas are thought to be good at providing prognostic information. In other words if your PET scan midway through treatment is negative you have an excellent prognosis for not relapsing. But more recent information is brining this into dispute. Not only do some studies show that those who have a positive PET scan still have a good prognosis, but there is increasing evidence showing that there is little consensus about whether a PET is positive, or negative. Some experts read it one way, and others read it the other way. There is no standardized method for interpreting the results of a PET scan. Here is a study regarding this problem, and another authors comments on the study.

• Interim positron emission tomography scans in diffuse large B-cell lymphoma: an independent expert nuclear medicine evaluation of the Eastern Cooperative Oncology Group E3404 study
• PET positive, PET negative, or PET peeve?

Here is another study that sheds some light on the value of mid-treatment PET/CT scanning. In summary they find that they are not necessary because a scan after treatment is over is just as good at predicting outcome. Therefore the extra radiation of a mid-treatment plan may not be a wise idea.

• Limited role of interim PET/CT in patients with diffuse large B-cell lymphoma treated with R-CHOP

Another challenge is that when a mid treatment PET scan is positive it is still not clear how to use this information to choose better treatments. Until that is possible PET scans are more informational than they are decisive.

• PET Scan Results of NCCTG N0489: Epratuzumab and Rituximab in Combination with Cyclophosphamide, Doxorubicin, Vincristine and Prednisone Chemotherapy (ER-CHOP) in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma
• Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography for Interim Response Assessment of Advanced-Stage Hodgkin's Lymphoma and Diffuse Large B-Cell Lymphoma: A Systematic Review
  
  
• Role of [18F]Fluorodeoxyglucose Positron Emission Tomography Scan in the Follow-Up of Lymphoma
• Response assessment after an inductive CHOP or CHOP-like regimen with or without rituximab in 103 patients with diffuse large B-cell lymphoma: integrating 18fluorodeoxyglucose positron emission tomography to the International Workshop Criteria
  
  
• The majority of transformed lymphomas have high standardized uptake values (SUVs) on positron emission tomography (PET) scanning similar to diffuse large B-cell lymphoma (DLBCL)
  
  
• Prognostic Value of Early 18fluorodeoxyglucose PET Scan in Patients with Diffuse Large B Cell Lymphoma Treated with Rituximab Plus CHOP or High-Dose CHOP
  
  
• A prospective study of the separate predictive capabilities of 18[F]-FDG-PET and molecular response in patients with relapsed indolent non-Hodgkin’s lymphoma following treatment with iodine-131-rituximab radio-immunotherapy

 

What are the limitations on PET scans

Like any type of diagnostic test, PET scans have limitations such as false positive results. But perhaps the biggest limitation is that although PET scans provide excellent prognostic information they don't always provide any information that will help or change the treatment recommendations. A test is only as good as the benefits it can provide. If you have a bad PET scan and you ask the doctor, "How should we change my treatment plan based on this scan?" If the doctor replies, "The scan does not change the treatment strategy." then what was the point of the scan.

Below are some studies which examine these limitations.  The first and second studies below have quite surprising results. In the first study after 4 cycles of R-CHOP patients with DLBC had a mid-treatment PET scan. All patients with a positive PET scan were required to have a repeat biopsy to confirm the finding. Surprisingly of the 38 PET positive patients 33 of them turned out to be negative by biopsy. Clearly PET is not perfect and false positives are common.

• Risk-Adapted Dose-Dense Immunochemotherapy Determined by Interim FDG-PET in Advanced-Stage Diffuse Large B-Cell Lymphoma 
• ¹⁸FDG PET/CT after intensified chemo-immunotherapy in diffuse large B-cell lymphoma (DLBCL), aged 18-65 with aaIPI 2-3 positive or indeterminate lesions are often false-positive: A Nordic phase II substudy
• Strikingly high false positivity of surveillance FDG-PET/CT scanning among patients with diffuse large cell lymphoma in the rituximab era 
• Poor Predictive Value of FDG-PET/CT Performed after 2 Cycles of R-CHOP in Patients with Diffuse Large B-Cell Lymphoma (DLCL)
• High incidence of false positive PET for aggressive NHL
• False positive PET scans with mediastinal lymphoma
• Early Pre/Post Fluoro-Deoxyglucose Positive Emission Tomography (PET) Does Not Predict Outcome of Patients Undergoing Hematopoietic Stem Cell Transplantation in Hodgkins Disease and Non-Hodgkins Lymphoma
• Prognosis Value of [18f] FDG-PET Prior Versus after Autologous Stem Cells Transplantation in High Grade Non-Hodgkin’s Lymphoma
• The Baseline PET SUV Correlates Better with Clinical Outcome Than the Post-Therapy PET Scan in Previously Untreated Patients with Histologically Aggressive Non-Hodgkin Lymphoma (NHL)
• Positron emission tomography in mantle cell lymphoma
  
  
• 18F-fluorodeoxglucose (FDG) positron emission tomography (PET) versus FLIPI as a predictor of therapy response in follicular lymphoma (FL) patients.

Prayer For Patience

Father, let us be quiet in Your presence long enough to see You fight on our behalf. I pray that I might trust You to go before me, to work out situations and problems where there appear to be no good options. Help me to know when to act and when to wait; when to shout and when to stand still.

Come to all of us and win victories in our personal lives, and in all our relationships. Help us to submit until we are willing to be patient, waiting for You to resolve difficulties that are beyond us.

I pray that I might not lash out and fight my battles out of fear, anger, or resentment but to take the time to submit to Your timing. May I believe that You care and will come to aid all who wait before You.

“Wait patiently for the Lord.”

In Jesus’ name,

Amen.

Abridged, Moody Church, Chicago, IL

Ibrutinib receives FDA boost

Great news! Ibrutinib, the experimental drug that my wife, Mary Jo's, nephew has been taking as part of a clinical trial at Vanderbilt has taken another step towards general availability

Less than a year after the Food and Drug Administration began accepting applications for “breakthrough therapy” designations to fast-track promising new drugs, regulators have approved just 11 of 35 requests from pharmaceutical companies.

Three of those approvals, however, have gone to one niche market cancer drug that Raritan-based Janssen Pharmaceuticals is developing with Pharmacyclics Inc. of Sunnyvale, Calif.

The drug, called Ibrutinib, has so far proved effective at blocking three different types of blood cancers in patients who had relapsed several times after taking existing therapies. The FDA designations are for chronic lymphocytic leukemia, mantle cell lymphoma and Waldenstrom’s macroglobulinemia.

Industry analysts say Ibrutinib has mostly flown under the radar because of its small market, but still believe it holds significant potential for its unique technology and relatively mild side effects.

Last week, the FDA granted Ibrutinib its latest breakthrough designation to treat CLL, one of the most common forms of adult leukemia that affects about 16,000 Americans a year. The disease, a slow-growing cancer that starts in the white blood cells, targets the elderly, with an average survival of about five years.

Clinical trials have shown Ibrutinib is effective for all CLL patients but works particularly well in those with a rare form of the disease that makes them immune to chemotherapy treatment, said Adrian Wiestner, a senior investigator at the National Institutes of Health in Bethesda, Md., who is overseeing one of the studies. That 52-patient study has shown “dramatic improvement for patients who otherwise had run out of options,” Wiestner said.

The other two diseases that received FDA designation affect a smaller population of adults than CLL.

A breakthrough designation is intended to expedite the development and review of a drug for serious or life-threatening conditions, according to the FDA. The drug in development must show early clinical evidence that demonstrates substantial improvements over existing therapies.

A majority of patients who took part in Ibrutinib’s two clinical trial phases are still in treatment, up to two years later without relapse, said Craig Tendler, vice president of Janssen’s oncology late stage development. Janssen is a unit of New Brunswick-based Johnson & Johnson.

Results have not been released for its third and final clinical trial phase.

Taken in pill form — one a day — Ibrutinib is also more tolerable than traditional chemotherapy medicines, Tendler said. He attributes part of Ibrutinib’s success to “the selectivity of this drug over other available therapies.” Most traditional medicines, he added, are “a combination of chemotherapy regimens that are often toxic and have short remission. This keeps the disease under control. Its potential is really transformational.”

Read the entire article here:

Bad News Is Actually Good News

 I was to start the Ibrutinib trial soon specifically for Waldenstroms at Northwestern Univ. I got a call from the trial coordinator, she told me I have bad news, that is actually good news. The trial got canceled because of the "Breakthrough" status. Because "Breakthrough" is new, no one really knew what it meant.

Apparently it means Ibrutinib is being approved immediately in a limited way for CLL, Mantle Cell and Waldenstroms. The institutions that participated in the e arly Trial willbegin to prescribe Ibrutinib soon. It will soon be available to all institutions. This drug has been so successful, it is being rushed to market.

So instead of having to drive to downtown Chicago and go through the involved trial process, with CT scans BMB's etc. I can simply take the drug on a daily basis and get tested periodically.

 There are trials in process for the big ones as well, DLBCL, FNHL as a singleagent as well as in combination with Rituxin etc.

 Mark 55 Chicago