Children diagnosed with retinoblastoma and low-grade gliomas have a likelihood of long-term survival exceeding 90 percent. Two studies published recently in Cancer provide insights that can help manage long-term patient care and follow-up for these cancer survivors.
Researchers from Memorial Sloan Kettering Cancer Center report that survivors of retinoblastoma have an increased risk of chronic conditions compared with non-retinoblastoma controls; however, after excluding ocular conditions and second malignant neoplasms, this excess risk was found to persist only for those with bilateral disease, which is often associated with germ-line mutations (Friedman et al. Cancer. Published online: 11 JAN 2016 DOI: 10.1002/cncr.29704). In fact, survivors affected unilaterally rated their general health as "excellent to good" in the study, suggesting that they maintain comparatively normal health years after completing therapy.
The second study, from Case Western Reserve University School of Medicine, used data from the Childhood Cancer Survivor Study to investigate long-term effects of blindness in children with low-grade gliomas. Surprisingly, it showed that vision loss in childhood had little psychological effect when patients reached adulthood (De Blank et al. Cancer. Published online: 11 JAN 2016 DOI: 10.1002/cncr.29705). But bilateral blindness was associated with an increased risk of being unmarried, living with a caregiver, and being unemployed.
Chronic Conditions Not Widespread
Survivors of retinoblastoma have an increased risk of chronic conditions compared with non-retinoblastoma controls. In the study from Memorial Sloan Kettering, after excluding ocular conditions and second malignancies, this excess risk was found only among patients with bilateral disease.
The retrospective study included adult survivors of retinoblastoma diagnosed between 1932 and 1994. Participants completed a comprehensive questionnaire adapted from the Childhood Cancer Survivor Study surveys. The researchers compared outcomes of 470 survivors of retinoblastoma with 2,377 non-retinoblastoma controls and found that 54 percent of survivors of retinoblastoma had bilateral disease at the time of diagnosis.
At a median follow-up of 42 years, 86.6 percent of survivors of retinoblastoma had at least one chronic medical condition, and 71.1 percent had a severe/life-threatening (grade 3-4) condition.
In survivors with bilateral disease, after excluding ocular conditions and second malignancies, the investigators found a relative risk of 1.2 for any chronic health condition compared with controls, and a 1.7 relative risk for severe/life-threatening conditions. But there was no increase in the risk of chronic health conditions-excepting non second malignancies and ocular problem-among survivors with unilateral disease.
The two most common severe/life-threatening conditions were loss of hearing and thyroid nodules requiring partial or total thyroidectomy. Because 70 percent of survivors had received external-beam radiotherapy to the primary tumor, the researchers believed that hearing and thyroid-related abnormalities may have been due to radiation exposure to otherwise healthy tissue.
"We asked what problems-besides the well-known problem with second malignancies-these retinoblastoma survivors are dealing with as they approach middle age," said first author Danielle Novetsky Friedman, MD, a general pediatrician in the Pediatric Long-Term Follow-Up Program at Memorial Sloan Kettering Cancer Center. "And I was pleased to learn, in formal way, that the relative risk isn't very much higher than in the controls."
Friedman said the take-home message is that these patients need continued close followup for second malignancies, hearing loss, thyroid problems, and side effects that might be related to the types of treatment received.
"Retinoblastoma survivors need lifelong multidisciplinary treatment from clinicians, oncologists, opthalmologic oncologists, and primary care providers who are aware of these risks and can monitor them," she said.
Friedman acknowledged the help of two senior researchers instrumental in making the data available: David H. Abramson, MD, Chief of the Ophthalmic Oncology Service, Department of Surgery at Memorial Sloan Kettering, and Ruth A. Kleinerman, MPH, Assistant Branch Chief and Staff Scientist, National Cancer Institute Division of Cancer Epidemiology & Genetics.
Blindness Not Associated with Adverse Cognitive, Emotional Outcomes
The Case Western Reserve researchers investigated the long-term effects of blindness in children with low-grade gliomas, based on data from the Childhood Cancer Survivor Study, a multi-institutional retrospective cohort study of five-year survivors of childhood cancer who completed comprehensive questionnaires regarding a wide range of health-related outcomes.
Among 1,233 survivors of astroglial tumors, 277 (22.5%) had vision impairment, with no vision in one eye or amblyopia; 47 survivors (3.8%) were legally blind. The focus of the retrospective study was the psychological and socio-economic outcomes of patients affected by limited or no vision.
Compared with low-grade glioma survivors without visual impairment, survivors who were legally blind were more likely to be unmarried (odds ratio 4.7), live with a caregiver (odd ratio 3.1), and be unemployed (odds ratio 2.2).
But surprisingly, legal blindness was not found to be associated with adverse cognitive and emotional outcomes, and there was no difference in outcomes noted between survivors with some compromised vision and those with normal vision.
First author Peter M. K. de Blank, MD, Assistant Professor in the Division of Pediatric Hematology and Oncology, Case Western Reserve University School of Medicine and UH Rainbow Babies & Children's Hospital, noted that in about one-third of cases, current chemotherapy treatments improve vision in children with brain tumors involving visual pathways; another third will have their vision stabilized; and another third will have their vision deteriorate despite intense treatment.
"We hope this study will help inform therapeutic decision-making as patients consider the risks and benefits of therapy," de Blank said. "And for the third of patients whose vision will continue to deteriorate, this study gives new information to patients' families and clinicians who are involved in deciding whether and when to start therapies for gliomas that affect vision. And it gives hope to families who have vision loss even after our best therapies."
De Blank said he started this research because he follows many patients with neurofibromatosis type 1, which has a predisposition to low grade gliomas in the optic pathway.
"These gliomas very rarely threaten life, but they threaten vision in about 50 percent of patients," he said.
The treatment discussion with such patients and their families is usually about trying to preserve vision, and discussing the agents that will be used in treatment.
"The question is, what will happen if we can't preserve vision despite our best therapies?" he said. "These patients are often ones we've been following for a while, watching the vision slowly deteriorate, and then we start talking about what the next step is."
De Blank said he was surprised that survivors who still had some vision remaining did not seem to have poor psychological or socioeconomic outcomes.
"Remember that we were looking at just some measures of socioeconomic status and we can't say with a broad stroke that those patients weren't affected at all," he said. "But for the measures we've been looking at for a long time in the Children's Cancer Survivor Study, there is not a statistically significant difference (from controls), and that is great news.
"If there is a case with an optic pathway glioma or a tumor affecting vision, but affecting it only in a single eye, we might say that tumor is still worth treating because we don't know if the tumor and the patient's vision will get worse. But if you can't fix the vision, the patient can still feel that going on with life with a single eye is pretty darn good."
Lessons Learned
An editorial, "Looking back to inform the future: Lesson learned from childhood cancer survivors," accompanied these two studies (Armenian, Bhatia. Cancer. Published online: 14 JAN 2016 DOI: 10.1002/cncr.29703).
"Follow-up studies such as these not only provide us with valuable information regarding the overall health and well-being of survivors in active follow-up, but also set the stage for future comparisons regarding the efficacy and long-term benefit of newer treatment strategies in this growing population of survivors," said the authors, Saro H. Armenian, DO, Associate Professor, Departments of Pediatrics and Population Sciences, and Director of the Childhood Cancer Survivorship Clinic at City of Hope, and Smita Bhatia, MD, Division of Pediatric Hematology/Oncology, Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham.
"With the long-term survival expected for these individuals, it is important to understand the impact of vision loss, either unilateral or bilateral, on the long-term psychological and socioeconomic outcomes in survivors of optic pathway gliomas, which can potentially facilitate therapeutic decision-making," the authors wrote.
In an email exchange with OT, Bhatia said that the most important concern for patients with retinoblastoma and optic glioma is preserving vision and minimizing the burden of toxicity while maximizing cure.
"It is for this reason that we need to make sure we use therapeutic options not associated with long-term toxicity, such as external beam radiation, especially among the very young retinoblastoma patients who are very susceptible to the toxicity," she said.
Bhatia said both of these retrospective studies are relevant today even though they include data collected when older treatments such as radiotherapy were standard.
"Both studies demonstrate that the toxicities were not very high," she said. "This is very encouraging [since] the chronic toxicities with the newer treatments should be even fewer."
Tasks of Multidisciplinary Treatment for Retinoblastoma Survivors
* Screening;
* Blood work where indicated;
* Thorough and careful physical exams at each time point where clinicians see the patient;
* Counseling patients about future health risks, such as the need for skin monitoring for skin cancers, and discussing future potential genetic transmission to offspring.