The Oeffinger Study

An ESUN Article

Bruce Shriver, PhD
Editor-in-Chief, ESUN

A landmark study by Dr. Kevin Oeffinger and his colleagues, Chronic Health Conditions in Adult Survivors of Childhood Cancer, was published in the October 12, 2006 issue of The New England Journal of Medicine. Within a few days, articles offering different insights about the study and its results and conclusions began appearing. Among them are:

The articles undoubtedly began appearing immediately because of the main and overriding conclusion of the report, "Survivors of childhood cancer have a high rate of illness owing to chronic health conditions." What was this conclusion based on? It turns out, it was based on a substantial body of evidence as the Oeffinger study tracked "the health status of adults who received a diagnosis of childhood cancer between 1970 and 1986 and compares the results with those of siblings. We calculated the frequencies of chronic conditions in 10,397 survivors and 3034 siblings." This group of survivors (those who have survived for at least five years after treatment for childhood cancer) is the large and geographically diverse cohort followed in the Childhood Cancer Survivor Study, CCSS. The goals of the Oeffinger study were to determine: (1) the prevalence, incidence and severity of chronic health conditions in adult survivors of childhood cancer; and, (2) the risk of chronic conditions in the survivors as compared with their siblings. The study involved patients who had an original diagnosis of leukemia, central nervous system tumor, Hodgkin's disease, non-Hodgkin's lymphoma, Wilms' (kidney) tumor, neuroblastoma, soft-tissue sarcoma, or bone tumor. The results were not good: "A severity score (grades 1 through 4, ranging from mild to life-threatening or disabling) was assigned to each condition. Cox proportional-hazards models were used to estimate hazard ratios, reported as relative risks and 95% confidence intervals (CIs), for a chronic condition ... Among 10,397 survivors, 62.3% had at least one chronic condition; 27.5% had a severe or life-threatening condition (grade 3 or 4). The adjusted relative risk of a chronic condition in a survivor, as compared with siblings, was 3.3 (95% CI, 3.0 to 3.5); for a severe or life-threatening condition, the risk was 8.2 (95% CI, 6.9 to 9.7). Among survivors, the cumulative incidence of a chronic health condition reached 73.4% (95% CI, 69.0 to 77.9) 30 years after the cancer diagnosis, with a cumulative incidence of 42.4% (95% CI, 33.7 to 51.2) for severe, disabling, or life-threatening conditions or death due to a chronic condition." Importantly, the researchers found that female survivors had a 1.5 times higher risk of a severe chronic health condition than male survivors.

Groch noted that Oeffinger and his colleagues stated that there are several considerations to consider when interpreting their findings. She reported that, "First, the conditions were self-reported without external verification, except for death. Also, several key chronic conditions, such as late-onset cardiomyopathy, associated with previous anthracycline exposure, may remain clinically silent for long periods. Other conditions that may be under-reported are osteoporosis, hypertension, and insulin resistance. A notable omission in the comprehensive list of chronic conditions in this study is adverse mental health outcomes, an important component of morbidity after childhood cancer."

Rosoff cautions us by pointing out that, "There is an unavoidable and noteworthy deficiency in the data from the CCSS cohort. All the patients were treated before 1986, and there have been considerable changes in therapy for most childhood cancers during the succeeding 20 years, often with an escalating intensity of treatment paralleling an improvement in survival rates." Rosoff goes on to say, "At the same time, we have become increasingly aware of the potential for late effects and have attempted to incorporate this knowledge into treatment protocols whenever it is possible to do so without sacrificing efficacy. It would be expected that patients who were treated more recently might have an analogous but different array of long-term complications. This historical effect argues for establishing another cohort for future study."

Rosoff further observes that findings of the study, "imply that vigorous and long-term monitoring of young cancer survivors, accompanied by early intervention when problems arise, is mandatory. There is a dark side to being cured of cancer as a young person" and that "It would seem to be incumbent on us to ensure that survivors of childhood cancer are followed closely by physicians who understand the effects and outcomes of cancer treatment — who know what these patients have been through and what kinds of complications to look for in the future. Sadly, such follow-up is the exception rather than the rule.." Among some very interesting suggestions that Rosoff presents to the medical community (e.g., incorporating specific training into residency programs in internal medicine, pediatrics, and family medicine and developing postgraduate training fellowships in an adult subspecialty), he suggests that patients be given a "portable document" (e.g., a smart card) containing a description of "their treatment, its potential late complications, and any types of behavior that could diminish their risk of late effects."

I recommend that anyone interested in the late-effects of childhood cancer treatments, read the Oeffinger Study and the four additional, brief articles cited above.

 

Long Term Effects of Cancer Treatments

We have previously reported on the long term effect of cancer treatments in "The COG Survivor Guidelines: A View from the Pediatric Sarcoma Perspective." One of the important resources discussed in Dr. Joan Darling's article is the Children’s Oncology Group's Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers. COG summarizes these guidelines as follows:

The Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers were developed as a collaborative effort of the Nursing Discipline and the Late Effects Committee. The purpose of these guidelines is to provide recommendations for screening and management of late effects that may potentially arise as a result of therapeutic exposures used during treatment for pediatric malignancies. These guidelines represent a statement of consensus from a panel of experts in the late effects of pediatric cancer treatment. The recommendations are based on a thorough review of the literature as well as the collective clinical experience of the task force members, panel of experts, and multidisciplinary review panel (including nurses, physicians, behavioral specialists and patient/parent advocates). Implementation of these guidelines is intended to increase awareness of potential late effects and to standardize and enhance follow-up care provided to survivors of pediatric malignancies throughout the lifespan.

The Long-Term Follow-Up Guidelines were developed as a resource for clinicians who provide ongoing healthcare to survivors of pediatric malignancies. A basic knowledge of ongoing issues related to the long-term follow-up needs of this patient population is assumed. The screening recommendations in these guidelines are appropriate for asymptomatic survivors of childhood, adolescent, or young adult cancer presenting for routine exposure-based medical follow-up. More extensive evaluations are presumed, as clinically indicated, for survivors presenting with signs and symptoms suggesting illness or organ dysfunction.

In a sidebar in Dr. Darling's article, we also identified the University of Michigan's webpage, Long Term Follow-Up Study. The webpage describes various aspects of the Childhood Cancer Survivor Study (CCSS), which they summarize in the following way:

The Childhood Cancer Survivor Study (CCSS) was created to take advantage of that opportunity and to help discharge that obligation. The CCSS is a component of the Long-Term Follow-Up Study. A collaborative, multi-institutional study funded by the National Cancer Institute, the CCSS is composed of individuals who survived five or more years after treatment for cancer, leukemia, tumor, or similar illness diagnosed during childhood or adolescence. The CCSS, which includes all participants in the Long-Term Follow-Up Study with a confirmed diagnosis of cancer, is a retrospectively ascertained cohort of 20,346 childhood cancer survivors diagnosed between 1970 and 1986. It also includes approximately 4,000 siblings of survivors who serve as the comparison group for the study. The CCSS cohort has been assembled through the efforts of 27 participating centers in the United States and Canada. It is coordinated through the University of Minnesota, Department of Pediatrics and Comprehensive Cancer Center. Other core facilities include the Statistical Center, located at the Fred Hutchinson Cancer Research Center (Seattle); the Biopathology Center (Columbus); and the Radiation Physics Center at MD Anderson Cancer Center (Houston). Initiated in 1993, the study is funded by a grant from the National Cancer Institute.

We also identified in Dr. Darling's article the Survivorship webpage of Candlelighters Childhood Cancer Foundation. Among other things, you can access a list of Comprehensive Long Term Follow Up Clinics from this webpage. Lastly, we identified the Survivor Issues webpage of the Ped-Onc Resource Center. This is a resource well worth exploring.

Beyond the Cure is a program of the National Children's Cancer Society. It was created for survivors of childhood cancer. Current research indicates that over two-thirds of childhood cancer survivors experience at least one "late effect" as a result of their disease or treatment. Late effects, the results of diagnosis and treatments, can vary in severity, but may include secondary malignancies, as well as problems associated with heart, endocrine, sensory or reproductive systems. Cancer also affects a person emotionally, developmentally, cognitively, spiritually and socially.

Another helpful study is "The Impact of Chemotherapy on the Survival of Patients With High-grade Primary Extremity Liposarcoma." This article was written by Eilber, Fritz C., Eilber, Frederick R., Eckardt, Jeffery, Rosen, Gerald, Riedel, Elyn, Maki, Robert G., Brennan, Murray F., Singer, Samuel,and appeared in Annals of Surgery. 240(4):686-697, October 2004. Abstract: Objective: To determine if chemotherapy offers a survival benefit to patients with large, high-grade, primary extremity liposarcoma. Summary Background Data: The impact of chemotherapy on the survival of patients with primary extremity soft tissue sarcoma is controversial and its effect on individual histologic subtypes is not defined. Patient and Methods: Two prospectively collected sarcoma databases were used to identify all patients with >5 cm, high-grade, primary extremity liposarcoma that underwent surgical treatment of cure from 1975 to 2003 (n = 245). Clinical, pathologic and treatment variables were analyzed for disease-specific survival (DSS), distant recurrence-free survival (DRFS) and local recurrence-free survival (LRFS). Conclusions: In patients with large, high-grade, primary extremity liposarcoma; DOX is not associated with improved DSS and IF is associated with an improved DSS. Treatment with IF should be considered in patients with high-risk primary extremity liposarcoma.

We are familiar with two online support groups for survivors of childhood cancer.

For survivors of chondrosarcoma, osteosarcoma, Ewing's bone sarcoma and other bone sarcomas, we recommend Adult Bone Cancer Survivors (a.k.a., ABC Survivors). Survivors post their stories on the site, and there are online support groups to find such mentors. The site is specifically limited to adults with primary bone cancer. It also contains a list of bone cancer resources.

 

V3N5 ESUN Copyright © 2006 Liddy Shriver Sarcoma Initiative.