Harmonization of big data in examining acute and long-term outcomes with contemporary treatment for pediatric and adult patients with Hodgkin lymphoma is yielding a new approach to inform future clinical trial design and enhance clinical decision-making, according to a statement by Rutgers Cancer Institute of New Jersey. Results from the Hodgkin Lymphoma International Study for Individual Care (HoLISTIC) were shared as part of a poster presentation during the ASCO20 Virtual Scientific Program.1
Andrew M. Evens, DO, MSc, FACP
In an interview shared by Rutgers Cancer Institute, Andrew M. Evens, DO, MSc, FACP, commented about the findings and discussed the development of the international consortium known as HoLISTIC that contributed to the basis of the study. Dr. Evens is Associate Director for Clinical Services and Director of the Lymphoma Program at Rutgers Cancer Institute of New Jersey and Medical Director of Oncology Services at RWJBarnabas Health, with facilities throughout New Jersey.
Although Hodgkin lymphoma is associated with good rates of overall disease control, its treatment includes a significantly increased risk of treatment-related late effects including secondary malignant neoplasms and cardiovascular disease, compromised health-related quality of life, and the potential loss of young lives.
Due in part to these factors, substantial debate remains over the optimal treatment of individual patients in the modern era, including the type and amount of chemotherapy, use of radiation therapy, use of interim positron-emission tomography to guide response-adapted therapy, and integration of novel therapeutics (eg, antibody-based, immunotherapy). Helping clinicians and patients assess the individualized treatment tradeoffs of acute and long-term outcomes of alternative treatment options at the time of initial diagnosis is desired.
About the International Consortium
Susan K. Parsons, MD, MRP, of Tufts Medical Center, Boston, and Dr. Evens spearheaded the formation of HoLISTIC, which currently consists of 55 worldwide pediatric and adult oncology experts in Hodgkin lymphoma, decision science experts, statisticians, epidemiologists, patient foundations, and advocates. Individual patient data are being collected from 16 prominent, contemporary clinical trials of patients newly diagnosed with Hodgkin lymphoma and also 6 large institutional/regional Hodgkin lymphoma registries, the latter of which are enriched with long-term follow-up and late-effects data, Dr. Evens noted.
The group’s overall goal is to improve clinical decision-making for pediatric and adult patients with cancer, given expanding treatment options but imperfect future knowledge about long-term outcomes with contemporary treatment (ie, 20-to-30-plus years after therapy). To accomplish this, Dr. Evens said, “we are assembling the best available evidence, including detailed information from recent prominent [Hodgkin lymphoma] clinical trials, ‘real-world’ Hodgkin lymphoma registries, and established Hodgkin lymphoma survivorship cohorts into one harmonized database.”
Key Findings and Implications
In the analysis presented during the ASCO20 Virtual Scientific Program, Dr. Parsons and investigators performed successful linkage of the harmonized HoLISTIC data set of individual patient data on patients with Hodgkin lymphoma younger than age 30 with simulated estimates of late effects from the large St. Jude LIFE pediatric Hodgkin lymphoma cohort, based on cumulative treatment exposures.2 Patient-level data on cumulative chemotherapy doses were extracted from the harmonized HoLISTIC database for 982 patients with Hodgkin lymphoma (mean age = 19 years) from five clinical trials treated with chemotherapy alone and who survived at least 5 years progression-free.
A microsimulation model was set up, by incorporating mortality and incidence of late effects as functions of diagnosis age, sex, race, treatment exposures, and attained age estimated from 5,522 adult 10-year survivors of childhood cancers in the St. Jude LIFE cohort. Despite differences in acute progression-free survival, reflecting in part the variation in risk/stage status, the projected long-term outcomes were similar.
According to investigators, the model will allow for personalization and incorporation of evolving new therapies and knowledge to emerge that will help providers identify the options best aligned with patient values and preferences. This project’s results will be significant, as they are expected to enhance individualized patient care, (economic) value, and ultimately outcomes. In addition, this approach will inform the development of similar methods, treatment models, and paradigms for other cancers.
Dr. Evens remarked: “We will continue to harmonize individual patient data from 16 large, contemporary clinical trials, conducted in North America and Europe across the age continuum and disease spectrum (ie, pediatrics and adults; and early and advanced stages) from more than 12,000 Hodgkin lymphoma patients.3 Employing principles of data science and modeling, we will estimate acute survival rates and project long-term risks for individual patients across alternative treatment strategies.”
Altogether, using data already acquired through data-sharing and international collaboration across pediatric and adult specialties, the group plans to create robust and innovative decision models to guide patients with Hodgkin lymphoma and their families, along with their providers, to provide granular, objective data to enhance and optimize the difficult decisions that impact acute and long-term outcomes.
The models will also allow for incorporation of updated information as new therapies and knowledge emerge. Finally, the decision model will be converted to a Web-based platform to test and evaluate among providers and patients with Hodgkin lymphoma at the point of care to help providers identify the options best aligned with patient values and preferences.
1. Parsons SK, Bhakta N, Rodday AM, et al: Lifelong disease burden of chemotherapy in Hodgkin lymphoma: A simulation study from the St. Jude Lifetime Cohort and HL International Study for Individual Care (HoLISTIC). ASCO20 Virtual Scientific Program. Abstract 12068.
2. Bhakta N, Liu Q, Ness KK, et al: The cumulative burden of surviving childhood cancer: An initial report from the St. Jude Lifetime Cohort Study. Lancet 390:2569-2582, 2017.
3. Evens A, Advani R, Aleman B, et al: The Hodgkin Lymphoma International Study for Individual Care (HOLSTIC): A Multi-National Collaborative to Enhance Decision Making for Pediatric and Adult Hodgkin Lymphoma (HL). EHA25 (European Hematology Association); abstract EP1149.