Managing Pain

Pain.

Little scares a new oncology patient as much as the idea of pain.  Unfortunately, pain permeates my practice.  Often, pain is the initial symptom that leads to a new cancer diagnosis.  Cancer patients undergo frequent painful procedures -- biopsies, bone marrow aspirates, surgeries ... even a simple blood draw involves a small amount of pain.  Because of this, managing pain is something I have some experience doing.

So I was surprised when I read this article in The Washington Post this morning and discovered that "some [pain doctors] began decrying the increasingly widespread use of opioids and questioned whether the drugs worked."  Really?  There are pain doctors who question whether opiates (morphine, for example) work?

Over the years, I have seen a variety of pain management styles. From doctors who prescribe intramuscular injections of pain medications to small children recovering from surgery, through sophisticated regimens involving patient-controlled analgesia and the use of non-drug techniques designed to specifically combat different types of pain. Pain management skills vary widely, and careful use of appropriate therapies can make all the difference to a suffering child.

Unfortunately, because the drugs which are the mainstay of pain treatment, opiates, are highly addictive, their use is politicized.  The article in today's Washington Post, for example, was focused on a patient advocacy group, the American Pain Foundation, which gets the lion's share of its funding from the pharmaceutical industry.  Unfortunately, this creates the appearance of a conflict of interest when the group strongly advocates for the use of specific narcotic pain medications (such as OxyContin) to control chronic pain.  And the appearance of a conflict of interest, whether or not the conflict exists, is sufficient to cast doubt on everything the Foundation has to say, even when what they say is spot on.

The use of narcotic pain medications is clearly expanding, and as a result, overdoses are an increasingly common cause of death in this country.  That doesn't mean these drugs should not be used.  They are highly effective at controlling acute, and even chronic, pain.  But like all medications, they need to be used appropriately, under medical supervision, prescribed by doctors who are experienced in their use, know how they work, know what kinds of pain they help, and know the risks and limitations of their use.

The diseases I treat cause pain.  One of the most common fears among cancer patients is the fear of dying in pain.  The treatments I use cause pain.  Some of the procedures we perform to monitor the progress of my patients cause pain.  Without highly effective drugs to treat pain, I could not do my job.  Rather than politicizing these drugs, we should be advocating for increased education about their proper use, about choosing the right drug for the right type of pain, and increasing research into the mechanisms of pain so that newer, more effective, safer drugs can be developed.

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Rare But Serious

The patient and her parents were hardly focused on what we were saying.  Not surprising, since she was still recovering from the news that the pain in her leg was not from a sports injury, but from osteosarcoma.

Kameron was a high school athlete, and now, instead of anticipating a college scholarship to play hockey, she was anticipating a year's worth of chemotherapy and a major leg surgery.  She and her parents were in the office, listening (but probably not hearing) to the side effects she should expect from her upcoming chemotherapy.  At the end of the conference we discussed some of the "rare but serious" side effects, like fertility loss and heart failure.

Fertility loss is something that catches people's attention.  To some extent, so does heart failure.  But for adolescent patients, somehow infertility feels more "real."  So we talked about her possible future fertility problems much more than we talked about her heart.

Throughout her therapy, we monitored heart function with regular testing.  All of the tests were reassuring.  But one day, soon after her treatment was done, Kameron developed chest pain.  When treatment for reflux and then for infections didn't make things better, she came to the emergency room, and that is when we discovered she was in heart failure.

These side effects, the "rare but serious" ones, are some of the hardest for us to deal with.  Kameron's cancer prognosis is excellent.  I am optimistic she will become a survivor.  Unfortunately, she paid a huge cost to survive her cancer.  When she leaves the hospital, she will be on heart medicine for the foreseeable future.  She may even end up needing a heart transplant.  This is not a problem that is just going to go away, and for the rest of her life, Kameron will not only be a cancer survivor, but also a heart patient.

This is what drives us to work hard in the lab for treatments that won't come at such a high price to our patients. 

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Yoga – Not Just for Skinny, Pretty Women Anymore?

This post is dedicated to a close friend of mine, a budding scientist with an aversion to yoga.

The benefits of yoga for cancer patients were plastered throughout the popular press recently, in anticipation of a presentation by Dr. Karen Mustian from the University of Rochester Medical Center at this year’s meeting of the American Society for Clinical Oncology in Chicago. This study enrolled 410 cancer survivors (96% female, 75% had breast cancer) suffering from moderate or worse sleep disturbance. The participants were randomized to standard monitoring versus a 4 week yoga intervention. Participants in the yoga program had improvements in sleep quality, fatigue, and various measures of Quality of Life compared with the control arm (no intervention). The benefit was significant enough to be covered by mainstream media outlets like CNN as well as web-based media like Breastcancer.org. ASCO president Douglas Blayney, MD, stated that the results are “readily applicable” for a huge patient population.

But wait. As we scientists often ask, do the results support the conclusions?

I think the answer is a resounding “Maybe.”

There is mounting evidence that cancer survivors benefit from participating in yoga programs. Although this study is the largest thus far reported, it is certainly not the first to show a benefit to yoga. Back in 2003 a study presented at the ASCO meeting showed that participation in a yoga intervention improved the Quality of Life of women newly diagnosed with breast cancer.

But is it yoga, per se, that helps? So far none of the studies have compared participation in yoga with any other exercise program. This study, for example, published in 2001, demonstrated that a home-based walking exercise program improved fatigue and other Quality of Life measures in women being treated for breast cancer. The studies cited on this page of the American Cancer Society’s website demonstrate a benefit to using a treadmill or an outpatient wellness program involving aerobic exercise, strength training, flexibility and relaxation. So maybe it’s exercise in general, and not specifically yoga, that helps cancer survivors live better.

Are the results of the yoga study “readily applicable” to a huge patient population, as suggested by Dr. Blayney? Again, I think the answer is “Maybe.” It depends on how you define “a huge patient population.” Dr. Mustian’s study is certainly applicable to the very large number of women diagnosed with breast cancer every year, but her study involved essentially only women with breast cancer. Given the variety of ways various cancers are treated, it may be premature to conclude that because yoga helped these women, that it would make a difference for young adults being treated with intensive chemotherapy for leukemia.

So what can we conclude? I think it is safe to conclude that some degree of exercise is beneficial for cancer patients, probably regardless of where they are in the course of their therapy. But before we can state that yoga is the best form of exercise, the right study has to be performed: patients need to be randomized to various forms of exercise, and research participants need to include men as well. Perhaps for a relatively inflexible man like me, the frustration of not being able to do “downward dog” will make yoga a poor choice, while the feeling of accomplishment associated with being able to last 5 more minutes on the treadmill will make that form of exercise a much better choice. Only a well-designed experiment can tell us for sure.

 
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How Small a Chance Is Too Small?

I’ve written about difficult cases before, but this case is really eating at me. It touches on issues of patient autonomy and how much influence we, as physicians, have over our patients. But the real issue is one of futility. How small a chance at survival is too small to offer a very toxic treatment?

The patient is a young boy with leukemia. We have been treating him for over a year, and his leukemia just won’t go into remission. For the past 3 months he has been in the hospital, first to receive chemotherapy and then to manage the side effects we caused. His bone marrow is nearly empty, but almost 80% of what few cells are present are leukemia cells. His only potential curative therapy is a bone marrow transplant.

Therein lies the problem. Not only does he have refractory leukemia, but his lungs are significantly injured from his previous chemotherapy, functioning at just about 55% of their predicted ability. For my patient, this is a major problem, because sick lungs make a bone marrow transplant very risky. Also, he doesn’t have a matched donor, so we would have to do a highly experimental type of transplant called a “reduced intensity haploidentical transplant.” This means we would give less than the usual amount of chemotherapy (to try to decrease the toxicity), and would use a donor that is only half matched.

I presented this case to the adult BMT group last week. Not one of them thought going through with the transplant was a good idea. They are convinced the patient will do badly, that he will end up dying in the ICU on a ventilator, and would never be cured with this approach anyway. Better to send him home on hospice care.

I polled a number of pediatric colleagues by email. They all said the same thing – better to do hospice care than a transplant that will most likely make the patient sicker before he dies anyway.

Our group has discussed the case extensively. We all agree that the chance of cure for this child is less than 5%. There is a 95% chance he will die faster and in more pain if we go ahead with the transplant than if we send him home on hospice care. So is the more humane choice to not offer the family a transplant, knowing the odds are overwhelmingly against success, knowing that the transplant will most likely make an already tragic situation worse?

Who gets to decide if the 5% chance of a cure is worth the risk? Is this chance of success so small as to qualify as futile?

If I know the father the way I think I do, if I hold out ANY chance of cure, he’ll take it, no matter the cost. That means, if I offer the family the transplant, he will go for it. But is that fair of me? He doesn’t know what it’s like to watch a child die in the ICU. I don’t think I can fully explain to him how awful a death his son may have, especially compared with what it would be like for him to die peacefully at home. Given that, can he truly give informed consent?

On the other hand, if I don’t offer the transplant, I take away even that slim chance of survival. Can I ethically do that? Or is that a decision the parents get to make?

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Why David Hates Health Insurance Companies

A Rant

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I am involved in a case right now that epitomizes all that is wrong with commercial health insurance.  All in one case.  How convenient.

My patient is a young adult with a sarcoma diagnosed in her liver.  There is one large mass and several smaller ones.  The tumor is not resectable right now, so she will need chemotherapy.

Two issues have arisen this week:  one related to diagnostic imaging (radiology) and the other related to quality of life.  With both issues I have faced significant roadblocks, placed by the patient's insurance company, that impede my ability to provide the care this young woman needs.

I'll start with the imaging issue.  The patient's sarcoma is not one that typically arises in the liver.  Also, the presence of multiple masses is more consistent with spread TO the liver, rather than the tumor arising FROM the liver.  That means, if we hope to cure this young woman, we need to find the primary tumor.  A CT scan of her chest, abdomen, and pelvis showed nothing.  An MRI of her pelvis, to better evaluate her uterus, a place that this tumor could arise, showed nothing.  Because a tumor like she has can come from anywhere in the body, I ordered a PET scan.  The insurance company denied coverage.

Why?

Because, the physician reviewer told me, there is no evidence that a PET scan is useful in this disease.

Of course, the physician reviewer is not an oncologist, and therefore not a sarcoma specialist, so I'm sure he does not keep up with the latest literature about PET scans and sarcomas.  But I do.  A quick search of PubMed using the terms "sarcoma" and "PET" revealed 471 articles.  I faxed him 4 of them yesterday.  I hope that is sufficient evidence to allow me to get the test I, the treating physician, believe my patient needs in order to maximize my chance of curing her.  I'll find out later today or tomorrow.

The other roadblock involves her quality of life.  My patient will need a chemotherapy drug called ifosfamide to treat her tumor.  This drug has a significant risk of infertility associated with it.  After consultation with a reproductive endocrinologist, we decided that the best was to try to protect her fertility would be to use a drug called Lupron.  Unfortunately, Lupron is expensive, so it requires prior authorization from the insurance company.  I just received an email from our clinic coordinator that read, in part, "It won’t be covered if it’s for fertility reason (per her case manager)."

So... I have some choices to make.  Do I lie and say the drug is being prescribed for another indication?  Do I tell the truth and risk the family having to pay $750 per dose out of their own pockets?  Or do I choose a different drug, one that will not work as well, and know that I am not providing optimal care for this young woman, and am increasing her risk of infertility?

All because her health insurance company wants to save a few bucks.  At least they are "not for profit."  Imagine the difficulties we face when the insurance company is trying to provide dividends for their investors, instead of health care for their customers.

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More About Patients and the Press

I have blogged before when stories about my patients (and their families) appeared in local newspapers. But this time it’s different. This time, my patient is the author!

Let me explain.

Phil (he gave me permission to blog about this) was receiving radiation therapy at another institution. He was suffering one of the common side effects – burning skin. Realizing that the redness and burning are caused by inflammation, he had a clever idea. With the permission of his radiation oncology team, he tried an over the counter anti-inflammatory cream. It worked! His skin improved dramatically.

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The best part is what Phil did with this experience. He didn’t just tell his treating team. He didn’t just tell his friends. He wrote a case report describing the experience, and with the help of his radiation oncologist, he published it. In a journal called “The Oncologist.”

You can read the paper here, but only if you have a subscription (or are accessing the internet from an institution with one).

Most doctors say that we learn from our patients. But how many have read articles in the medical literature authored by our patients?

Way to go, Phil!

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Taking Control

I’ve mentioned before how much I enjoy PostSecret. This is a site that posts anonymous postcards containing about a secret about the writer. Today’s update had this postcard:

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This card reminded me of a topic that comes up with almost every new patient I see. I am inevitably asked, “When will my child’s hair fall out?” Both parents and children usually ask what they should do about it. Like I discussed in July, I always refer them to our Image Recovery Center, where they can learn techniques for maintaining a healthy self-image from cancer survivors.

But do you know what most of my adolescent and young adult patients do? Not only do they visit the Image Recovery Center, but in an effort to maintain some control over their body, they cut their hair short or shave it off altogether! What a healthy response to knowing your treatment will rob you of your hair. Taking control of whatever can be controlled is important. Feeling in control is so much better than feeling out of control – whether you are being treated for cancer or jumping out of an airplane.


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A new old remedy for nausea

I am often asked my opinions about herbal remedies. Patients seem more attuned than ever to alternative therapies, but many still want a physician’s opinion about what does and does not work.

Giving an educated opinion is often a challenge, because rarely are herbal remedies tested in traditional medical trials. With the introduction of the National Center for Complementary and Alternative Medicine, a part of the National Institutes of Health, this was supposed to change. Slowly, but surely, it is.

Last week, in advance of the upcoming meeting of the American Society for Clinical Oncology, results from a number of studies scheduled to be presented were released to the public. One of these was designed to test whether ginger, a traditional folk remedy for nausea, can help with the nausea produced by chemotherapy.

No one suggested that ginger alone was sufficient, but instead, patients were who experienced chemotherapy-induced nausea were randomly assigned to one of four groups: 1) treatment with their regular anti-nausea drug alone, 2) treatment with their regular anti-nausea drug plus 0.5g ginger, 3) treatment with their regular anti-nausea drug plus 1.0g ginger, or 4) treatment with their regular anti-nausea drug plus 1.5g ginger. The ginger was administered in the form of a capsule containing ginger extract, and neither the patients nor their doctors knew who was in what group. Patients reported their daily nausea on a 7 point scale. A total of 664 patients were treated, 90% women, 66% with breast cancer. All doses of ginger significantly reduced the nausea patients experienced while receiving chemotherapy. You can read the original abstract here.

So what does this mean? Ginger may interfere with blood clotting, so patients should still consult with their doctors prior to adding this to their routine, but on the whole ginger is safe and effective. And if the form doesn’t matter (something not tested in this trial), imagine how easy it would be to convince patients to add ginger in the form of ginger ale or cookies! Of course, not all ginger ale contains actual ginger – and artificial ginger flavoring is unlikely to be a good substitute.

What else does it mean? I think it reinforces something I tell all of my patients who ask about herbal remedies. Some work, some don’t. The ones that work should withstand the sort of testing we do for other medical treatments, including the “gold standard,” a double-blind, placebo-controlled study. Just like this one. Ginger passed the test.

I’m going to go make my patients some ginger snaps!

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Could Your Heart Medicine Cause Cancer?

There was a series of interesting articles in the last issue of the New England Journal of Medicine concerning a heart medicine called Vytorin. Perhaps you’ve seen the ads on TV. You know the ones… they show high cholesterol foods and a silly looking person dressed to look like the food to reinforce the idea that Vytorin has 2 medicines to address 2 ways your cholesterol could become elevated. In fact, Vytorin is a combination of Simvastatin, a drug that works by blocking your body’s ability to make cholesterol, and Ezetimibe, a drug that works by blocking your body’s ability to absorb cholesterol from the foods you eat.

In theory, this is a great idea. After all, cholesterol comes from 2 sources, why not create a drug that affects them both? This is exactly what Merck and Schering-Plough did in a joint venture using drugs that each company still had under patent.

Having created this drug, the pharmaceutical companies had to get the approval of the FDA to market it. Otherwise, they could not have aired those memorable ads. To earn FDA approval, a drug company has to provide data from a clinical trial showing the drug’s effectiveness. Vytorin was approved based on its ability to lower blood levels of LDL, the "bad cholesterol" that is associated with heart attacks and strokes. After FDA approval, the company launched another study called the ENHANCE study. This study was designed to show an effect on atherosclerosis ("hardening of the arteries"). It lasted just 2 years and enrolled 720 patients with a genetic disorder (familial hypercholesterolemia) that causes high cholesterol levels and heart attacks and strokes at a very young age. The study showed that Vytorin lowers cholesterol levels in these patients, but it did not detect a decrease in heart attacks or strokes.

Importantly, the study did not show that Vytorin was any better than Simvastatin alone.

There have been 2 drug company-sponsored trials since then: the SEAS trial (SEAS stands for Simvastatin and Ezetimibe in Aortic Stenosis) and the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) trial. Both studies were designed to test whether Vytorin reduces the risk of heart attacks and strokes better than Simvastatin alone. The results of the SEAS trial were released this week (The IMPROVE-IT trial is still ongoing). In a disappointment for the drug companies, Vytorin did not decrease the risk of progression of aortic stenosis (a narrowing of the valve leading from the heart into the aorta, the major artery that drains the heart) or on cardiovascular events in general.

Surprisingly, the patients taking Vytorin had an increased risk of cancer compared with patients taking a placebo.

What’s going on here? Does this new heart medicine not only not work, but also cause cancer?

The answer is probably not that simple.

When the data from all 3 trials are combined, there is no increase in the incidence of cancer in patients who take Vytorin. However, there was an increased risk of dying from cancer.

How could this happen?

Well, one possibility is that this is just a coincidence. The studies were not designed to detect a risk of getting or dying from cancer. So maybe it was a statistical fluke.

But it could be real. An editorial in the New England Journal accompanying the articles warns about this possibility. Ezetimibe inhibits the absorption of plant sterols from the diet, not just cholesterol. Epidemiologic studies have linked diets high in plant sterols to a lower incidence of cancer. Laboratory animals (mice and rats) fed a diet high in plant sterols show modest resistance to chemical carcinogens and to tumors grown from injected human cancer cells. Plant sterols have a number of inhibitory effects on human cancer cells grown in the lab. These findings could provide the basis for a plausible biological explanation for the results in the SEAS study.

I wrote this piece for two main reasons: one reason is that I think this case (and the fiasco surrounding Vioxx) is an important reminder not to be so eager to take a new drug just because it’s new and has a cute ad. FDA approval is no guarantee that a drug is safe, and some relatively rare but certainly very significant side effects only become noticed during what is called post-marketing surveillance. The other reason is as a teaser for my upcoming, first ever book review: Reasonable Rx: Solving the Drug Price Crisis, by Finkelstein and Temin.

Stay tuned.

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This topic was also covered extensively by one of my friends in another blog. Read her posts here and here.

Cancer and Self-Image

Cancer and its treatment cause big changes in how patients look. Sometimes a tumor is visible and directly alters the patient’s appearance. Some cancer surgeries are disfiguring. Chemotherapy causes hair loss. Chronic steroid use can change the way a patient’s face looks. Cyclosporine, used to prevent and treat graft-versus-host disease, causes hair growth in unusual places.

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These changes can be even more profound when the patient is a child. Radiation causes bones to stop growing, so as the rest of the child grows, the irradiated bones do not, and scoliosis or other changes can develop. Chronic steroid use impairs growth. Bone marrow transplantation and brain radiation cause significant hormonal changes whose importance is magnified in the developing child or adolescent.

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Adolescence is a time when appearance is terribly important and often central to a person’s developing self-image. Imagine, then, how hard it can be to be diagnosed with cancer and then be treated for it when you’re that age – when all you want to do is fit in!

What can be done about this? One important source of help is people who have been through it before. One woman, Marianne Kelly, started a program in Baltimore called Image Recovery Centers. Ms. Kelly was diagnosed with a brain tumor in 1987, and that experience, along with the experience of losing a sibling to leukemia and having a daughter diagnosed with leukemia, led her to work with cancer patients to help them maintain a positive self-image despite the changes caused by their diagnosis and the treatments they need. I send my patients to the Image Recovery Center at our hospital as often as I can.

Another source of support can be the stories of patients who cope particularly well with the effects of their cancer treatment. My patient M, for example, dyed her hair purple (and sometimes pink or blue) as it grew back after she lost it during chemotherapy.

My favorite story, though, is about Warren (not his real name). Warren was 9 when he was diagnosed with retinoblastoma, cancer arising in the back of the eye. Most retinoblastoma patients are infants, and Warren is the oldest retinoblastoma patient I have ever cared for. When he was diagnosed, his tumor was so advanced that there was no hope of saving the vision in his right eye, so it was removed, a procedure known as “enucleation.” After healing from the surgery, Warren received a prosthetic eye. The prosthesis was so real looking, that one of my colleagues had to ask Warren which eye he had lost!

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But the best part of the story is not the quality of his glass eye, but what Warren did with it. The first summer he had the eye, he spent a lot of time swimming in his pool. While other kids in the neighborhood would toss a penny into the pool to dive after it, what did Warren and his friends dive for? You guessed it – his eye!

How’s THAT for making the best of what life gives you?

(Follow this link to see how easy it is to remove a prosthetic eye)

For more information about coping with the effects of cancer treatment, click here for beauty and comfort tips from the Image Recovery Center at Johns Hopkins.

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When Benign Isn’t Better and Malignant is Preferred

I take care of people with tumors. Often, I’m the one who tells them their diagnosis. Sometimes, it’s a disease they haven’t heard of, so one of the most common questions I get is, “Is it benign or malignant?” As you might imagine, everyone wants their tumor to be benign. Benign is better, right?

Not always.

At the moment, I’m struggling with a very difficult case. X is a teenager who has had a tumor for 5 years. In the beginning he had some pain and a lump on the side of his head. A biopsy was thought to show a lymphangioma (a benign collection of abnormal lymph vessels). The mass continued to grow, so he had surgery to decrease the size of the tumor. When that tissue was removed, the pathologist thought it was something called a granular cell tumor (also benign). Unfortunately, it grew back, and this time it damaged his eye enough to make him blind (in that eye). He had a larger surgery which relieved some of the pain and pressure, but only temporarily.

Now the tumor has grown even bigger. It was biopsied earlier this month. This time the pathologist can’t make a diagnosis. It’s been sent to other national experts for their opinions. It may still be benign. Is that a good thing? Not necessarily.

If it’s benign, it won’t respond to chemotherapy. If it’s benign, it may not respond to radiation. And yet, it’s still causing him pain and it’s still disfiguring. He misses a lot of school and is very self-conscious about his appearance.

If it’s benign, the only therapy that will help is surgery, and given how many times this tumor has grown back, it will require a complete resection to cure. And a complete resection will remove half his face. Literally.

What if it were malignant? If it were malignant, we could use chemotherapy and/or radiation before surgery. This would probably shrink the tumor significantly. Then it could be removed with a much less disfiguring operation.

I have another patient, about the same age, who has a rhabdomyosarcoma (cancer of skeletal muscle) in about the same place. Who is worse off, the patient with cancer, or the one with a benign tumor? Well, the patient with cancer has a 90% chance of being cured with a combination of chemotherapy and radiation, with minimal cosmetic consequences. The patient with the benign tumor may not die of his disease (although he could), but is in terrible pain and will require a horrific disfiguring surgery to get rid of the tumor.

Slides from X’s most recent biopsy are being reviewed at another hospital right now. I hope they diagnose a malignancy.

Cancer Treatment and Fertility, Part 2: What Can Be Done?

On April 1st, I wrote about the impact of cancer treatments on fertility. I discussed the many ways in which the way we treat cancer can affect the patient’s ability to have kids in the future. Fortunately, there are many things we can do to try to preserve fertility.

Part 2: What can be done to preserve fertility?

Some fertility preservation techniques are well-known. One option for boys who are old enough is sperm banking (freezing and storing their sperm for possible future use). Ideally, this should begin prior to treatment and multiple samples should be preserved. Unfortunately, in some cases this is not possible, due to the urgency of beginning treatment, especially in leukemia patients who are often quite sick at the time of diagnosis. Despite the common use of sperm banking, the use of frozen sperm seems to be rare (for example, only 7% of testicular cancer patients used their stored sperm in one study).

What about children who are too young for standard sperm banking techniques? Although the testes of younger boys may be relatively spared from the effects of chemotherapy, this point is debated. In younger boys, sperm can be obtained by “electroejaculation” or by testicular sperm extraction (both under general anesthesia, of course).

These approaches work for boys whose infertility risk comes from systemic chemotherapy. As I discussed before, newer surgical techniques have made male infertility as a consequence of retroperitoneal lymph node dissection quite rare. What about radiation therapy? If the radiation must be directed at the testes, nothing can be done other than sperm banking. However, if only one testis must be irradiated, the other can be moved out of harm’s way surgically, and put back where it belongs when the radiation treatment has been completed.

A similar approach, called oophoropexy, can be used to move ovaries our of the radiation field in girls or women who need pelvic radiation. This can be done by a minimally invasive approach, using a scope. Unfortunately, damage to the uterus from radiation may still make pregnancy difficult or impossible.

Eggs (oocytes) can also be frozen and stored, just like sperm. Unfortunately, this is not as easily accomplished as it is in boys, and is not as successful. Oocytes can be retrieved directly (this requires drugs to stimulate their production and a minimally invasive procedure to harvest them), or ovarian tissue containing the oocytes can be extracted surgically and frozen. During cancer treatment, suppression of ovary function with medicines such as Lupron is probably also effective at preserving fertility, though this is not yet conclusively proven.

And what of the babies?

Given the number of options available to try to protect fertility, as well as the active research that will hopefully improve things in the future, we also have to give thought to the children who are born to survivors of childhood cancer. Chemotherapy and radiation therapy are mutagenic. Does that mean children born to people who receive these treatments are at increased risk of birth defects? Apparently not. A very large epidemiologic study published in 1995 failed to show a link between cancer therapy and developmental problems.

Hopefully, future therapies will have less impact on fertility than the treatments we have now, and we doctors will be able to look back on this time and be grateful our patients no longer have to add “Will I be able to have a baby?” to their list of worries when they are diagnosed.

Photo Credit

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Cancer and Fertility: How Can Treatment Impact Fertility? (Part 1)

“Uh, doc…”
“Yes?”
“Uh… I was just wondering… Did the chemo make it so I won’t be able to have kids?”

As my physician readers all know, it’s the question that is asked as the patient is walking out the door that often reflects what is most on his/her mind.

This snippet happened as my 20 year old survivor of metastatic Hodgkin’s Lymphoma was leaving the clinic last week. It raises a very important point… now that pediatric oncologists are curing ¾ of our patients, we have to worry more and more about the harm we do in the process. One of the biggest concerns of my patients (those old enough to care or understand) and their families (no matter how young the patient is) is future fertility. I’ll talk about this in two parts: Part 1 - what the risks are, and Part 2 - what can be done about it.

Part 1: Risks of Infertility

Although we mostly think of chemotherapy and radiation therapy as the primary causes of infertility, there is evidence that some cancers can impair fertility even before treatment. For example, Hodgkin’s lymphoma is associated with impaired sperm production pretreatment in 2 of every 3 male patients. The mechanism for this finding is unclear.

Surgery, radiation, and chemotherapy can all result in reduced fertility in both men and women. Men who require extensive removal of abdominal lymph nodes (bilateral radical retroperitoneal lymph node dissection) universally have nerve damage that results in dry ejaculation (in other words, no ejaculate fluid). Fortunately, such procedures are now rare, and nerve sparing techniques have reduced this risk to less than 10%.

Radiation therapy to the pelvis can impair fertility in a number of ways. Irradiation of the testes is directly toxic to sperm, and doses of 4-20 Gy (the abbreviation for gray, a unit for measuring the amount of radiation delivered) or higher can cause permanent loss of sperm production. Lower doses will cause a transient decrease in sperm production that will recover with time. Interestingly, the Leydig cells, cells of the testis that produce testosterone, are relatively resistant to radiation, so testosterone production (and therefore sexual development and function) will be normal even if no sperm are produced. In women, pelvic radiation can impair fertility not only by killing oocytes (eggs), but also by damaging the uterus, making it difficult to become pregnant, to carry a pregnancy to term, or for the fetus to grow to a normal size (intrauterine growth retardation). Unfortunately, because girls are born with all of the oocytes they will ever have, as girls age, the dose of radiation that causes infertility falls steadily.

Chemotherapy is a major cause of fertility problems in survivors of childhood cancer. Not all chemotherapy is the same, though, which is an important point when counseling patients about their fertility risk. So-called alkylating agents (cyclophosphamide, ifosfamide, busulfan, procarbazine, and others) have the highest rate of gonadal toxicity. Cisplatin, carboplatin, and doxorubicin have an intermediate level of risk, and vincristine, vinblastine, dactinomycin and bleomycin carry a lower risk (see Table 2 here).

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As with radiation therapy, in boys the cells that support sperm production (seminiferous epithelium) is very sensitive to chemotherapy, while Leydig cells are relatively resistant, so again, boys may develop normally but fail to produce sperm. Girls are less susceptible to the toxic effects of chemotherapy than boys. Although fertility may be less compromised, premature menopause is not uncommon in girls who receive chemotherapy. Byrne et al found that 42% of women who were treated with radiotherapy and alkylating chemotherapy drugs (such as ifosfamide, cyclophosphamide, and procarbazine) before age 20 had reached menopause by age 31.

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All of that sounds pretty grim. It is important to keep in mind, though, that fertility difficulties don’t strike everyone. One of the first patients I took care of as a fellow was a teenaged boy diagnosed with Hodgkin’s Lymphoma, notorious for resulting in infertility both because of the disease and because of the treatment. We talked about his fertility risks, but I warned him not to count on the chemo as birth control. I’m not sure he heard that part, because two years later he came for a follow-up appointment with his girlfriend and their baby!

Next time… Part 2 - what we can do to preserve fertility.