Innovative Radiotherapy Controls Late Effects in Hodgkin Lymphoma in Pediatric and AYA Patients

Innovative Radiotherapy Controls Late Effects in Hodgkin Lymphoma in Pediatric and AYA Patients
Innovative Radiotherapy Controls Late Effects in Hodgkin Lymphoma in Pediatric and AYA Patients

Radiotherapy is a highly effective modality for the local control of Hodgkin lymphoma and is commonly included in combined-modality treatment regimens. Concerns about late effects—particularly for children, and adolescents and young adults (AYA)—have fueled advances in radiotherapeutic planning and delivery, including the recent development of involved site radiotherapy (ISRT). This review introduces ISRT and its emerging role in Hodgkin lymphoma management.

Radiotherapy is frequently identified as the “most effective single modality” for local control of most types of lymphomas, and its role in lymphoma treatment (typically as part of a combined-modality approach) has been called “one of the great successes in modern cancer treatment.”1 For decades, early stage classical Hodgkin lymphoma has been treated with combined chemotherapy followed by consolidative radiotherapy,  but primary radiotherapy is also used for these patients.2

The goal of modern radiation oncology is to deliver therapeutic radiation doses to tumor volumes while sparing healthy nontarget tissues, to minimize toxicities and morbidities. Conceptual and technological innovations to better achieve that goal have included advanced 3-dimensional functional and anatomic imaging for treatment planning, and conformal and intensity-modulated external-beam radiotherapy such as 3dCRT and IMRT.

The risk of long-term radiation toxicities and late effects such as secondary malignancies—particularly in patients treated as children or AYAs—has been a source of controversy.1-4 The role of consolidative radiotherapy has been seriously challenged in early stage favorable classical Hodgkin lymphoma among adolescents and adults, for example.2

In pediatrics and in young adults, clinicians should remember that with the use of consolidative radiotherapy, “the late effects to normal organs may follow many years thereafter,” notes Carol Portlock, MD, of the Memorial Sloan Kettering Cancer Center in New York.2 Patients (or caregivers) should be educated to understand benefits and the long-term risks of the treatment regimen.

There are no firm guidelines for organ-specific toxicities or late effects and their management for lymphoma radiotherapy, notes Portlock.2

Controversially, in some cases, concerns about late radiation effects have even led to the omission of radiotherapy in AYA patients with Hodgkin lymphoma.5 One 2015 analysis of data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) registry, found a significant decline in radiotherapy for AYA Hodgkin lymphoma between 1995 and 2010.5 The 5-year survival rate among AYA patients who underwent radiotherapy as part of treatment was superior to that of patients who did not undergo radiotherapy (97.7% vs 96.4% for 2003-2010; P=.02), the authors of that study reported.5 The cumulative risk of second malignancies among these patients at 150 months was nearly identical among AYA patients with Hodgkin lymphoma who underwent radiotherapy and those who did not (3% and 3.3%, respectively; P=.87, not significant).5 However, the risk of death without secondary malignancy was significantly higher among AYA patients for whom radiotherapy was omitted (8.8%) than for those who underwent radiotherapy (5.7%; P=.0009), prompting the study authors to conclude that “omission of radiotherapy for early classical Hodgkin lymphoma in AYA may increase mortality without reduction in secondary malignancies.”5

Nevertheless, minimizing the incidence of late radiation effects remains an important goal—one that has fueled innovations in Hodgkin lymphoma treatment and radiotherapy generally, integrating advanced anatomic and functional (for example, PET/CT) imaging for 3-dimensional treatment planning, with advanced radiotherapy-delivery approaches such as 3dCRT and IMRT. Extended-field and early involved-field radiotherapy strategies that irradiated larger volumes that included lymph node stations have similarly been rethought, and smaller-volume radiotherapy targets are now widely preferred, to include lymph nodes only when there is detectable involvement (such as can be detected with contrast-enhanced computed tomography imaging).3 This involved-node radiotherapy (INRT) is extremely conformal, but depends on the availability of optimal imaging, which is not always available.3

That has led to led to the development of an alternative, more conservative concept: involved-site radiotherapy (ISRT), which is intended for use when field-planning information is incomplete or suboptimal, allowing smaller tumor volume irradiation and hence, a lower risk of radiation acute and late toxicities and sequela. 1-4  

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