© Oxford University Press 2006.
NEWS |
Texas Case Raises Questions About Hodgkin Lymphoma Treatment in Children
The recent case of a 12-year-old girl who was removed from her home and placed in foster care to receive court-mandated treatment for her Hodgkin lymphoma has sparked questions about different cancer treatment approaches, parental autonomy in medical cases, and the doctor–patient relationship.
According to newspaper reports and the family's Web log, Katie Wernecke of Agua Dulce, Texas, was diagnosed with stage IIb Hodgkin lymphoma in January 2005 and promptly began chemotherapy. When her doctor at Driscoll Children's Hospital in nearby Corpus Christi prescribed radiation after four cycles of chemotherapy and a negative PET scan, the family objected, citing concerns about the harmful effects radiation may have on her growth and development and later risk for breast cancer.
Their objection led to intervention by the Texas Department of Family and Protective Services, which won a court order in June to place Katie with a foster family and for her to undergo treatment at the University of Texas M. D. Anderson Cancer Center in Houston. She remained in foster care, against her family's protests, until early November, when a new judge on the case overturned the June ruling. She is now back with her parents, having finished a second round of chemotherapy at M. D. Anderson, and has begun high-dose vitamin C therapy at a clinic in Kansas. Doctors involved in her case stated in court documents that treatment delays have reduced her chances of recovery from 80%–90% to 20%–25%.
Bernadine Healy, M.D., weighed in on the case in her June 27 column in U.S. News & World Report, titled "The Tyranny of Experts." She wrote, "Standard care regimens are not rigid directives chiseled in stone. They are evidence-based guidelines with some give." She pointed to seven-time Tour de France winner Lance Armstrong, who at age 25 was diagnosed with advanced testicular cancer. He found an oncologist that devised a treatment that was different from the standard therapy to spare his lungs and his mental and physical coordination so he could go on to make sports history. When the Werneckes said no to radiation therapy for fear of long-term toxic effects, no other options were offered.
Beyond the specifics of Wernecke's cancer, this controversial case brings up at least two important questions for doctors who treat young patients: Is radiation therapy a "must have" for patients with Hodgkin disease? And how do physicians deal with parents who object to recommended treatments for their children?
All of the researchers interviewed for this story noted that they could not speak about the Wernecke case specifically. They were unfamiliar with the details and her diagnosis. But they were willing to take sides on the role of radiation in Hodgkin disease, one of the most curable cancers in children.
The Cost of Curative Therapy
The Werneckes hit on one of today's unresolved issues in Hodgkin lymphoma treatment: Who needs radiation? Their concerns were well founded; there are clear toxic effects of radiation therapy. Hodgkin lymphoma tends to present in the chest and neck area. When radiation is used, the breasts and heart—as well as the lungs, esophagus, and stomach—have the potential to be exposed to radiation and its ability to cause second malignancies and weaken the heart.
Specifically, after 15–20 years, death from Hodgkin lymphoma in early and intermediate stages is exceeded by other causes of death, mostly secondary malignancies and cardiac deaths, according to a 2002 review by scientists at University Hospital in Lund, Sweden. A more recent study by National Cancer Institute scientists published in JNCI (see article, Vol. 97, No. 19, p. 1428, October 5, 2005) calculated that a woman who received radiation for Hodgkin lymphoma at age 25 had an almost 30% risk of developing breast cancer by age 55. A woman of the same age in the general population has a 3% risk of developing breast cancer by age 55. The younger the patient is when she receives the radiation therapy, the higher her risk for later breast cancer.
Dan L. Longo, M.D., National Institute on Aging, followed with a forceful editorial, calling the results "shocking." He continued, "the literature is quite clear that combined radiation therapy and chemotherapy does not produce a superior overall survival to chemotherapy alone in any stage of disease." In a follow-up interview by e-mail, he clarified his position: "My main point is that for at least 75%–80% of patients, chemotherapy alone is sufficient to cure the Hodgkin disease. I would reserve radiation therapy for the subset of patients who are unlikely to be cured by chemotherapy alone rather than exposing 100% of patients to the risks associated with radiation therapy."
"We are fortunate to have a variety of tools that are effective," he continued. "With long-term follow-up, it is quite clear that treatments that include radiation therapy as a component result in more deaths from the treatment than from the Hodgkin disease. Accordingly, I recommend using radiation therapy only in the minority of patients who require it to optimize their cure rate."
Some Controversy
But not all experts share the same opinion on whether to irradiate. "Many centers still use combined modalities," said Melissa M. Hudson, M.D., a pediatric oncologist at St. Jude Children's Research Hospital in Memphis, Tenn. "But every study in pediatric centers is trying to tweak and see who can eliminate radiation. We're very afraid to compromise and have relapse." She points to two recent studies with contemporary treatment for children showing that radiation can be of benefit, except for patients in very favorable risk categories. In 2002, the Children's Cancer Group compared low-dose, involved-field radiation treatment with no further treatment in patients who had achieved a complete response after risk-adapted combination chemotherapy. At 3 years, those who received radiation had an event-free survival advantage, but overall survival did not differ. Follow-up is admittedly short and will continue.
|
In a 2003 report, researchers at the University of Leipzig Medical Center in Germany gave two cycles of chemotherapy to patients with very favorable prognoses, four cycles for intermediate, and six cycles for higher risk. The chemotherapy combination differed for boys and girls. Patients who achieved remission (22%) were allowed to forgo radiation. Radiation doses for remaining patients varied with amount of response to treatment. Only the early-stage group fared as well with and without radiation. In the others, radiation improved event-free survival. They too await long-term results, including any difference in overall survival.
Some say radiation therapy has improved enough to make analyses like the October JNCI study (which covered treatment from 1965 to 1994) obsolete. "We're not using treatment today that we used in the 1970s," said Sarah Donaldson, M.D., professor of radiation oncology at Stanford University. "We do not expect to see those same kinds of [breast cancer] incidence numbers. The radiation today is very focused. The breast is seldom in the radiation field. Only the [upper outer quadrant] of the breast is in the [radiation] field if there is huge axillary disease, which is rare," she said. Radiation doses are lower as well.
|
However, the problem with the argument that radiation therapy is now better than it used to be is that "one cannot validate that claim until at least 20–30 years have elapsed so that one can tally the early and late side effects," Longo wrote in an e-mail. "There is no safe dose of radiation therapy and no method of delivering it that has been proven to be free of cancer risk. What we are always facing is a tradeoff of risk versus benefit. It is my position that the risk is higher than the benefit in the majority of patients."
Wyndham H. Wilson, M.D., Ph.D., chief of the Lymphoma Therapeutics Section at the National Cancer Institute, agrees. "The upshot of large meta-analyses is that, although radiation can sometimes reduce recurrence rates in some people, overall it doesn't improve survival because patients can be salvaged, retreated, and cured. I infrequently use radiation to treat Hodgkin [disease]. I avoid it," he said. "Radiation oncologists will say ‘we're using smaller fields, lower doses—it's not going to cause problems.’ That will reduce problems, but it can't eradicate them. If we can cure people without [radiation], that's a good way to go."
Risk-Adapt, Sex-Adapt
And because 80%–90% of Hodgkin patients survive their disease and live long into adulthood, research efforts have focused on reducing toxicity.
Hudson has written several editorials extolling the shift toward risk-adapted, sex-adapted therapy for pediatric Hodgkin lymphoma. Clinical staging using improved imaging modalities has replaced the riskier surgical staging using laparotomy and splenectomy. To try to reduce risk for growth deformities, cardiovascular problems, infertility, and second malignancies, radiation levels have been reduced and focused, and the mix and amounts of chemotherapy drugs are different from those used in adults and include a move away from alkylating agents and anthracyclines. Researchers have tried several approaches, each with merits and drawbacks.
Protocols today focus radiation on sites of bulkiest disease, according to Hudson. When the patient fails first-line therapy, she almost always fails in sites where disease existed at first diagnosis. "When you do chemo alone and don't use radiation, you need more cycles of more aggressive agents for a longer period of time," she said. "If you use supplemental radiation, you can use fewer drugs, fewer cycles, and less aggressive drugs. The whole package is designed to cure the child with the least side effects."
New studies are also trying to better define the response to treatment and potentially avoid radiation. Researchers at the University of Leipzig Medical Center in Germany launched a study in 2003 that is using fluorodeoxyglucose (FDG)–PET imaging to diagnose and to gauge response to treatment in children and adolescents. In patients with early-stage disease, radiotherapy is avoided in patients with a complete response or negative FDG–PET at the end of chemotherapy. The study will also replace procarbazine with dacarbazine in the COPP cycles (cyclophosphamide, vincristine, procarbazine, and prednisone) in an attempt to reduce sterility in males and premature onset of menopause in females.
An Emotional, Difficult Time
So what do oncologists do when their patients' parents balk at recommended treatment?
"On the face of it, hearing a parent say they want to avoid radiation in their child is a very reasonable statement," Wilson said. "But there may be situations where radiation is absolutely necessary in Hodgkin [lymphoma]." He recalled a recent visit where that wasn't the case. A family came to him in November seeking his opinion on whether their 17-year-old daughter should enter a randomized phase III pediatric study involving radiation for most patients. "I said I wouldn't go for it. In a 17-year-old girl with a mediastinal mass, do everything you can to avoid radiation. I'd do PET scans, chemotherapy, and see if you can't do this using chemotherapy alone."
Hudson has worked with families who want to avoid radiation. "I tell them, ‘Let's see the response to chemotherapy. If you have a tremendous response, we can try to avoid radiation. But I'd suggest we balance with some additional chemotherapy. We have to make up for the radiation we're not giving.’ " If, after chemotherapy, residual disease remains, "the plan is clear, the child needs radiation," she said.
She has also compromised with families. "One young woman was stage IV ... . She had 6 months of chemotherapy, alternating alkylating agent and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). She wanted no radiation after, even though she knew her risk was higher and she had bone marrow involvement. She was a college student and well informed. I told her it made me nervous, but if you feel strongly, let's do two more rounds of chemo. She's a long-term survivor. I've had others who, with or without radiation, have failed. Our ability to predict is pretty limited."
Longo has worked with patients who are Jehovah's Witnesses and refuse blood component therapy. In those cases, he said, "one must exert caution in using agents that can cause anemia or bleeding. The availability of appropriate marrow-stimulating growth factors has alleviated some of those concerns. I think parents are generally trying to do the best they can for their children, and if I encountered resistance to doing the best, I would refer the patient to someone else rather than administer therapy that I did not think was optimal," he added. "I don't know what others would do."
"Some families have, for whatever reasons, their own biases and don't want to have the recommended treatment," Donaldson said. "If it's life or death for the child—like a blood transfusion—sometimes those cases go to the court and a judge has to make the decision. We try to avoid that whenever possible by educating and giving lots of options. The real art in medicine is to educate and inform and be compassionate to parents' concerns, but not allow them to do a disservice to the child. The process usually works. It doesn't get you anywhere to enter a confrontational argument."
She continued, explaining that, as is true for most cancers, treatment decisions for Hodgkin disease come down to weighing the possible benefit of eliminating disease with the possible increased risk of second malignancies. "When I'm dealing with a young woman whose disease includes bulk in the mediastinum where radiation is recommended and the family is afraid of breast cancer, I talk about the likelihood of curing the Hodgkin disease. Many studies show that the cause of failure in patients treated with chemotherapy alone is that the disease comes back where it was to begin with. Treatment a second time around—high-dose chemotherapy with bone marrow transplant—is hugely aggressive with more side effects. When you look at the causes of death, number one is the Hodgkin disease—not breast cancer, stroke, or cardiovascular disease. The war against Hodgkin disease is the first war. Only if you're a survivor do you get to look at the second barrier."
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||