The COG Survivor Guidelines: |
A View from the Pediatric Sarcoma Perspective
An ESUN Article
Editor’s Note: Joan is a biologist. She is also mother of two, one of whom is an eight-year survivor of alveolar rhabdomyosarcoma. Joan spends much of her spare time as Co-List manager of the ACOR Rhabdo-Kids mailing list and as a Patient Advocate for the Children's Oncology Group.
A generation ago, the diagnosis of childhood sarcoma meant a very poor prognosis indeed. In the early 1970s the five-year survival rate for children with pediatric sarcomas was less than 30 percent. In the past thirty years, the survival rate has more than doubled to over 60 percent. Although clearly there is still a lot of progress to be made for those stages and types of sarcoma that show a poor outcome, for the first time in history a majority of children who had pediatric sarcomas can expect to reach adulthood. And most children who survive five years are in effect “cured”, with a long life ahead of them.
The better outcome is partly due to improvements in diagnosis and supportive care, but mostly it is the result of the development of aggressive, multi-modal treatment using combination chemotherapy for systemic disease control as well as surgery and/or radiation for local control. Unfortunately this success has come with a price. Survivors can be at risk for late effects (delayed side effects of treatment) that may not develop for many years. In some cases, these late effects can be life-threatening.
Standard Treatments for Pediatric Sarcomas
Pediatric sarcomas fall into four major groups. Two groups are bone sarcomas: osteosarcoma and Ewing's sarcoma; the other two are soft tissue sarcomas: rhabdomyosarcoma, a tumor of skeletal muscle, and other soft tissue sarcomas, usually lumped as non-rhabdomyosarcoma soft tissue sarcomas. Although all the sarcoma groups are somewhat heterogeneous, this last group is a grab-bag of diverse tumors with unique characteristics including synovial sarcoma, fibrosarcoma, malignant fibrous histiocytoma, and malignant peripheral nerve sheath tumor.
Most pediatric sarcomas are aggressive and highly malignant and require multi-modal treatment. Treatment for osteosarcoma typically entails surgery in combination with chemotherapy agents such as doxorubicin, methotrexate, cisplatin, and ifosfamide. In about ninety percent of the cases surgery is limb sparing, and treatment may include preoperative radiation or chemotherapy in an effort to reduce the size of the tumor (see the article, "Osteosarcoma", in the February 2005 issue of ESUN for more information).
Treatment for Ewing’s sarcoma frequently uses a five-drug therapy of vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide, as well as surgery and/or radiation therapy (see the article, "Ewing's Sarcoma Family of Tumors", in the June 2004 issue of ESUN for more information).
Treatment for most rhabdomyosarcoma uses a three-drug therapy of vincristine, actinomycin-d, and cyclophosphamide along with radiation and surgery if feasible (for more details see August 2004 ESUN). Treatment for other soft tissue sarcomas varies depending on the tumor type, but often involves surgery and radiation, and may include chemotherapy as well.
Patients with metastatic or relapsed disease may have been exposed to an even wider assortment of agents. For example, some Ewing’s patients may have had melphalan and busulfan (as part of preparation for stem cell transplant), and some rhabdomyosarcoma patients may have had irinotecan, topotecan, or doxorubicin, ifosfamide and etoposide.
Sarcoma Treatment Late Effects
All the components of treatment may have serious physical long-term effects. For example, doxorubicin is associated with cardiomyopathy (damage that weakens the heart) that may not develop for decades after treatment is completed. Radiation can cause secondary cancers, even another sarcoma. Some agents such as cyclophosphamide can cause infertility. Surgery can result in disabilities.
Psychosocial late effects can be just as devastating. Any cancer experience can cause a child to become depressed or suffer other emotional difficulties. Amputation or radiation to growing bones can result in self-image problems as the child matures. Some types of chemotherapy or cranial radiation may cause learning disabilities.
However, this is no reason to forgo treatment! Without treatment, most childhood sarcomas are inevitably fatal. And it is equally important to remember that many of these late effects are relatively rare, and may occur during a certain time period after treatment. For example, only a few percent of survivors will develop secondary leukemia, and the greatest risk is within five to ten years after treatment. Past that point, the risk drops off. But knowing that it is a possibility educates the patient of the risk and encourages him or her to contact a physician for symptoms of fatigue, paleness, or excessive bruising or bleeding that may be the first indications.
The key to successful treatment of late effects is often early diagnosis. Equally importantly, recognizing who is at risk may allow survivors to make life-style choices that reduce those risks. The problem is that many survivors, as well as their primary care physicians, may not be monitoring for these side effects because they are not aware of them.
It may be particularly complicated to monitor the health of pediatric sarcoma survivors. This is because unlike brain tumors or breast cancer or leukemia, or many other cancers associated with a particular organ system, sarcomas can occur pretty much anywhere in the body. The long-term effects resulting from treatment to control a rhabdomyosarcoma located in the pelvis will be very different from the side effects of treatment for a similar tumor located in the neck, even if the two children were treated on the same treatment regimen. If you factor in all the different treatment protocols for pediatric sarcomas over the years, the variability in late effects becomes even greater.
Children’s Oncology Group Survivor Guidelines
More and more people are survivors of childhood cancers as a result of the increased success in treatment. About three in one thousand children will develop some type of cancer by the age of twenty (Ries et al, 2005), and over 250,000 Americans (one in every thousand) are survivors of childhood cancer. As a result of steadily increasing survival rates, more of these are younger: currently one in 570 Americans between the ages of 20 and 34 are survivors; within a few years, it will be one in every 400.
Similarly within a few years one in every three thousand Americans will be survivors of pediatric sarcomas. The health of these survivors may depend on primary care physicians who understand the possible health problems caused by treatment. But with all the differences in treatment, and the relative rarity of sarcoma survivors, it’s unlikely the average physician would know what to be on the lookout for.
Until recently there was no evidence-based comprehensive guide to potential late effects from treatment for childhood cancers, and no authoritative recommendations for screening for late effects. The increased numbers of survivors made developing a guide an important priority of the Children’s Oncology Group (COG), the cooperative group that develops and implements clinical trials for pediatric cancers in the United States and Canada. The COG is the leading organization in North America of doctors and scientists dedicated to developing better treatments for childhood, adolescent, and young adult cancers. It includes over 200 member institutions, and is funded primarily by the National Cancer Institute.
In 2003, after more than two years of development, COG released the “Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers”. The guidelines were developed through the collaborative efforts of several COG committees, including the Late Effects, Nursing, and Patient Advocacy committees (Eshelman et al., 2004; Landier et al., 2004). Experts in many disciplines contributed their knowledge to produce consensus recommendations based both on evidence and on clinical experience. The guidelines are available online at CureSearch website or ask your oncologist or primary care physician for a copy of the pertinent information.
The guidelines are organized by treatment agent. Listed under the category of a specific chemo drug, operation, or radiation field are:
- Potential late effects
- Risk factors
- Patients at highest risk
- Tests to evaluate survivor’s health
- Recommended frequency of testing
- Suggestions to protect health
- Suggestions for further testing
The guidelines are intended to be used by pediatricians, internists, dentists, oncologists, neurologists, psychologists, endocrinologists, indeed anyone who provides health care to survivors, starting two or more years after treatment. They are not intended to detect recurrence or metastasis of the primary disease, but rather to improve survivor health care by providing information and raising awareness of possible late effects. Although these guidelines were created to monitor people who had cancer at a young age, they are likely applicable to older patients too, certainly until similar guidelines are developed for survivors of adult cancers.
If you are seeing a provider different than your treating oncologist, they will need to have a fairly detailed summary of what treatment entailed, including doses of chemo and radiation in order to use the guidelines. Many survivors do not have such a treatment summary, and I would recommend asking your oncologist for one, no matter what your age.
It is fairly easy to do the screening for most of the late effects. Most of the evaluation tests are likely to be included in an annual physical exam, and only a few require more detailed testing. It is a good idea to discuss the guidelines with your physician if you are concerned about testing for a particular late effect and whether consultation with a specialist is needed. More than any test, perhaps the most important part of long term follow up is your awareness of signs and symptoms, and a routine history and physical with a provider educated and alert to the possible long term side effects.
The COG guidelines also include an extensive reference section and Health Links. The Health Links are written for the patient and include late effects and risk factors, symptoms of problems, and actions survivors can take to stay healthy. The Health Links cover a wide range of topics, from kidney health to emotional issues to fertility to dental health. These Health Links arm the survivor/parent with knowledge that can empower the patient to self-advocate and work in conjunction with the providers to provider the best care after therapy, just as knowledge about sarcoma did during treatment.
It should be pointed out that as helpful as the guidelines are, they are based on limited data and they have not yet been validated on a large number of cancer survivors. Most screening guidelines (like mammography) have been tested on populations to confirm their efficacy and cost-effectiveness, so that there are not too many false positives (that engender unnecessary anxiety) or false negatives (that give a false sense of security). The COG has several taskforces of specialists working to update them regularly as new information becomes available. In addition, the guidelines are currently being computerized to allow creation of personalized guidelines for each survivor. If you have any comments or suggestions for improving the guidelines, please send a note via the comments and questions box below.
V2N3 ESUN Copyright © 2005 Liddy Shriver Sarcoma Initiative.