New cancer treatments and therapies pose exciting opportunities when it comes to improving care overall. But understanding the side effects, as well as the long-term late effects of those new and improved therapies, takes time.
A new study that analyzed long-term health outcomes in a group of 1,311 survivors of childhood medulloblastoma, who were diagnosed before turning 21, is an example. The data, published online ahead of print in the Journal of Clinical Oncology, follows patients diagnosed from 1970 to 1999 with a median follow-up of 21 years, ranging from 5 to 44 years (2019; https://doi.org/10.1200/JCO.18.00969). The researchers found that, while changes in medulloblastoma treatment over those 3 decades have improved survival rates, the rates of subsequent neoplasms and other severe health conditions have increased in modern survivors.
The researchers noted that survivors of medulloblastoma need to be closely monitored for these debilitating late effects and that more survivorship research and follow-up data are needed to better understand the longer-term effects of the newer modalities of medulloblastoma treatments used.
In an interview with Oncology Times, lead author Ralph Salloum, MD, Program Leader of the Young Adult Neuro-Oncology Program and Director of the Brain Tumor Survivorship Program at Cincinnati Children's Hospital Medical Center, stated: “Because of the inherently shorter follow-up of survivors from the 1990s, most comparisons in this study were limited to 15 years of follow-up. So, one question that remains unanswered is: what happens later as this survivor population ages?”
Salloum explains more about this study and why studying long-term and late effects of cancer treatment even decades later is important.
1 Your research analyzed patient data going back to the 1970s, which seems to speak to the value of tracking patients' outcomes over the long-term (via registries and cohorts). Is your research illustrative of this point?
“High-quality data regarding diagnosis, cancer treatment, and longitudinal follow-up of cancer survivors are essential in survivorship research. In this context, the Childhood Cancer Survivor Study with its expansion to include survivors across 3 decades (1970-1999) not only allowed us to evaluate long-term health outcomes of medulloblastoma survivors, but also offered a unique opportunity to explore the impact of temporal changes in therapy on major late effects among more than 1,000 survivors of medulloblastoma in a period when pivotal changes in treatment were made.
“A previous Childhood Cancer Survivor Study had shown an overall temporal reduction in late mortality attributable to late effects in survivors of childhood malignancies across 3 decades (1970-1979, 1980-1989, 1990-1999). Given that central nervous system tumor survivors are at the highest risk for late morbidity and mortality among pediatric cancer survivors, we aimed to focus this analysis on medulloblastoma survivors specifically in order to better understand these temporal trends and their association with treatment evolution during that era.”
2 The data you analyzed revealed some underappreciated risks that patients with medulloblastoma face over the long term. Why is this finding important?
“The evolution of medulloblastoma therapy from the 1970s to the 1990s (to include adjuvant chemotherapy and incorporate risk stratification) aimed to improve survival and minimize the risk for late effects of treatment. The key finding from this study is that, while survival of medulloblastoma has improved across these decades, historical changes in medulloblastoma therapy failed to minimize the risk for late effects.
“In fact, we found that more modern survivors have significantly increased risk for severe and life-threatening chronic health conditions and subsequent neoplasms. Fortunately, special education needs were lower for a subgroup of patients treated with reduced doses of craniospinal radiation.
“Currently, most children with medulloblastoma are cured as a result of the tremendous improvements in therapy that the pediatric oncology field has witnessed over the last 50 years. Unfortunately, we show that this cure comes at the cost of a spectrum of adverse outcomes that are experienced by survivors beyond 5 years from diagnosis.
“These late effects are rarely reported by pediatric cooperative groups and consortia whose primary goals are often cure rates, as they don't have the ability to follow their patients past 5 years from diagnosis. It is therefore our responsibility to report more consistently the delayed sequelae of treatment, including quality-of-life outcomes through studies like the Childhood Cancer Survivor Study. This is particularly important considering the longevity of pediatric cancer survivors and the potential implications that long-term follow-up research can have on frontline clinical trials and treatments.”
3 What's the bottom line practicing oncologists and cancer care providers should know about this research—particularly for those treating patients with medulloblastoma?
“Our research shows that medulloblastoma survivors remain at a high risk for late effects of treatment. We therefore need to focus modern therapy efforts on reducing risks for late effects for future generations. For example, this could be accomplished by reducing therapy in patients with favorable molecular and clinical features, introducing otoprotective agents in treatment regimens and using advanced radiation modalities such as proton beam therapy.
“Given that the risk for chronic health conditions from late effects of therapy remains very high even in modern survivors of medulloblastoma, we hope that this study also serves as a siren call to closely monitor these survivors and improve rates of screening and guideline-based follow-up.”