Kate Johnson

June 04, 2015

CHICAGO — Today's survivors of childhood cancer face a significantly reduced risk of dying from late effects of their disease, whether from a recurrence, a new cancer, or late toxicity from their treatment, a new study shows.

Results of the Childhood Cancer Survivor Study, which analyzed more than 34,000 children diagnosed from as early as 1970 through the 1990s, suggest that as cure rates for childhood cancers have improved significantly during the past 3 decades, the reduced toxicities of radiation and chemotherapy treatments have contributed to improved survival.

"We've not only helped more children survive their primary cancer, but we've also extended their overall lifespan by reducing the overall toxicity of treatment in more modern eras," explained lead investigator Gregory T. Armstrong, MD, MSCE, a pediatric oncologist at St. Jude Children's Research Hospital, in Memphis, Tennessee. He presented the research here at the plenary session of the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting.

"The translation of modifications in therapy designed to reduce exposure and to clinically significant reductions in all-cause late mortality is a gratifying validation of 3 decades of refining our therapies to accomplish the same number of cures while lowering the cost of cure," added the discussant for the paper, Michael Paul Link, MD, FASCO, from Stanford University School of Medicine, in California.

These results are indeed reassuring news. Dr Lars Hjorth

Approached by Medscape Medscape News for comment, Lars Hjorth, MD, PhD, pediatric oncologist at Lund University, in Sweden, and project coordinator of PanCareSurFup, a pan-European network investigating the serious long-term complications in 80,000 survivors of childhood and adolescent cancer, said the new findings are "in agreement with previously published data from the Nordic countries. Preliminary data from the EU-funded project PanCareSurFup was presented at the European Symposium on Late Complications after Childhood Cancer in Edinburgh in September, 2014. In this cohort of almost 75,000 5-year survivors, the trend of decreasing late mortality in the most recent treatment eras was once again shown. Together, these results are indeed reassuring news for those treated for childhood and adolescent cancer more recently."

Suvivors Living With Consequences of Treatment

One in every 750 adults in the United States is a childhood cancer survivor, said Dr Gregory. Work by his group has shown that 30 years after diagnosis, the greatest mortality risk these adults face is from the long-term effects of their treatment.

"Death due to recurrence of the primary cancer is not uncommon. However, risk of mortality due to recurrence or progression of primary disease plateaus by 15 to 20 years from diagnosis," he explained. "Deaths from external causes, including accidents, injury, and suicide, generally remain less than 1%, even after 20 or 30 years from diagnosis. However, we have identified that the mortality attributable to other health-related causes not only increases from time of diagnosis but by 30 years is the leading cause of late mortality."

Compared with the general population, survivors have a 15-fold greater risk for death due to new malignant neoplasms and a sevenfold increased risk for cardiac death, he said.

But results from his study show a significant reduction in these risks during the last 30 years.

From a cohort of 31 US and Canadian hospitals, the study identified 34,033 5-year survivors of pediatric cancer. The investigators used the National Death Index to assess mortality.

Forty percent of the patients were diagnosed before 4 years of age, with 23% diagnosed between ages 5 and 9 years and 37% between 10 and 20 years.

The most common diagnosis was leukemia (n = 10,199), followed by CNS malignancy (n = 6369), Hodgkin's lymphoma (n = 4332), Wilms tumor (n = 3055), bone tumors (n = 2930), non-Hodgkin's lymphoma (n = 2837), neuroblastoma (n = 2632), and rhabdomyosarcoma (n = 1679).

More than half (56%) were younger than 30 years at their last follow-up.

Treatment with radiotherapy declined significantly during the study period. In the 1970s, rates of chest, cranial, and abdominal radiation therapy were 33%, 39%, and 33%, respectively, compared with 19%, 19%, and 17% in the 1990s, said Dr Gregory.

Although the use of anthracyclines and alkylating agents increased from 27% to 58% and from 43% to 56%, respectively, the median dosage of both declined from 323 to 181 mg/m2 and from 7.7 to 7.2 g/m2, he added.

During the study period, the all-cause late mortality at 15 years from diagnosis dropped from 10.7% in the 1970s to 5.8% in the 1990s (P < .001).

Similarly, death from recurrence or progression of primary cancer dropped from 7.1% to 3.4% (P < .001).

And death from other health-related causes dropped from 3.1% to 1.9% (P < .001), including death from subsequent neoplasms (1.8% to 1.0%; P < .001), cardiac disease (0.5% to 0.1%; P = .001), and pulmonary disease (0.5% and 0.1%; P = .04).

These improvements were most striking in acute lymphoblastic leukemia (ALL), Hodgkin's lymphoma, and Wilms tumor, and can be attributed to reduced radiotherapy and anthracycline exposure, he explained.

For example, in the 1970s, 85% of ALL patients received cranial radiotherapy, 87% of Hodgkin's lymphoma patients received chest radiotherapy, and 78% of Wilms tumor patients received abdominal radiotherapy compared with only 19%, 61%, and 43%, respectively, in the 1990s.

Similarly, anthracycline exposure has decreased for all three diseases.

Compared with other oncologists, pediatric oncologists bear a special responsibility for reducing late treatment effects, Dr Link emphasized.

"While health effects of treatment with a long latency may never be seen in elderly adults cured of their cancer, children and young adults cured of cancer have a lifetime ahead of them, during which to develop all of the manifestations of those [treatment] health effects and to suffer their consequences," he noted.

Pediatric oncologists challenge themselves to improve the quality of life of survivors. Dr Michael Paul Link

"Pediatric oncologists challenge themselves to improve the quality of life of survivors. We look critically at our therapies in an attempt to determine those elements...necessary for cure in the hope of eliminating those components that contribute only to toxicity," he said.

Reacting to the study results, ASCO expert Stephen Hunger, MD, director of the Center for Childhood Cancer Research at the Children's Hospital of Philadelphia, in Pennsylvania, said, "For decades, we've strived to avoid the paradox in which children survive cancer, only to become sick or die years later because of the treatment they received. By carefully refining pediatric cancer treatment, we have improved long-term care and outcomes by leaps and bounds."

This study received funding from the National Institutes of Health. Dr Armstrong has participated in a speakers’ bureau, and one of his coauthors received research funding from Merck.

American Society of Clinical Oncology (ASCO) 2015 Annual Meeting. Abstract LBA2. Presented May 31, 2015.


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