2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

Refining the Role of Radiation Therapy in
Pediatric Hodgkin Lymphoma
By Melissa M. Hudson, MD, and Louis S. Constine, MD
Overview: The role of radiation therapy in the treatment of
pediatric Hodgkin lymphoma has continued to be refined,
motivated by the desire to avoid disruption to normal tissue
development and function and secondary carcinogenesis.
Such progress has occurred in tandem with modifications of
the multiagent chemotherapy regimens that have been used in
place of or in combination with low-dose involved-field radiation
that are also associated with dose-related risks of
cardiopulmonary and gonadal dysfunction and leukemogenesis.
Consequently, treatment strategies for young patients,
who have an excellent prognosis of long-term survival, utilizes
RADIATION THERAPY (RT) has played a seminal role
in improving outcomes for children and adolescents
with Hodgkin lymphoma (HL). Following delineation of a
tumoricidal dose, RT became the first modality to produce
prolonged disease-free survival when delivered to consistent
treatment fields of contiguous lymph nodes. Although curative
for a large number of patients with localized disease, its
combination with multiagent chemotherapy was needed to
improve long-term survival in individuals with advancedstage
and/or bulky node disease. Early RT approaches for
children and adults prescribed high doses (35–44 Gy) to
treatment volumes routinely extended to encompass adjacent
uninvolved nodal regions. Recognition of the adverse
effects of high-dose RT on musculoskeletal development in
children motivated investigations of multiagent chemotherapy
alone or in combination with lower radiation doses
(15–25.5 Gy) to reduce treatment volumes (involvedfields).
1,2 Increasing numbers of aging pediatric HL survivors
consequently permitted recognition of the excess risk of
cardiovascular disease and secondary carcinogenesis associated
with RT. 3,4 This knowledge led to the abandonment of
the use of RT as a single modality and its restricted use in
contemporary trials.
Research elucidating unique profiles of chemotherapyrelated
toxicity in children subsequently guided the development
of multiagent chemotherapy regimens that balanced
the dose-related toxicity of anthracyclines, alkylating agents,
and bleomycin, often by adding the modality of low-dose
involved- field radiation therapy (IFRT). Results from these
studies provide strong support for the responsiveness of HL
to a variety of multiagent chemotherapy combinations that
are largely derived from the original MOPP (mechlorethamine,
vincristine, procarbazine, prednisone) 5 and ABVD
(doxorubicin, bleomycin, vinblastine, dacarbazine) 6 combinations.
The desire to maximize treatment efficacy and
minimize its related long-term morbidity has increasingly
focused attention on the role of RT in the treatment of
pediatric HL. This manuscript aims to review published
data to define the optimal treatment strategies for children
and adolescents with HL in regards to the use of RT.
Prognostic Factors Used in Risk Designation of
Pediatric HL
As therapy for pediatric HL becomes more effective, factors
associated with outcome have become more difficult to
616
a risk-adapted approach that provides optimal efficacy for
disease control whereas limiting toxicity associated with both
radiation and chemotherapy. Because of the differences in
age-related developmental status and gender-related sensitivity
to chemotherapy and radiation toxicity, no single treatment
approach is ideal for all pediatric patients. This
manuscript summarizes results from published clinical trials
with the goal of defining optimal treatment strategies for
children and adolescents with Hodgkin lymphoma in regards
to the use of radiation therapy.
identify. Regardless, contemporary treatment for pediatric
HL uses a risk-adapted and response-based paradigm that
assigns the length and intensity of therapy based on diseaserelated
factors such as stage, number of involved nodal
regions, tumor bulk, the presence of B symptoms, and early
response to chemotherapy by functional imaging. In addition
to consideration of cancer-related factors that may
permit therapy reduction or require dose intensification, the
treatment approach may also consider unique host factors,
such as age and gender, that may enhance the risk for
specific treatment toxicities. Most protocols stratify groups
according to low-, intermediate-, and high-risk designations.
Low-risk clinical features typically include localized nodal
involvement in the absence of B symptoms and bulky disease.
Risk factors considered in other studies include the
number of involved nodal regions, the presence of hilar
adenopathy, the size of peripheral lymphadenopathy, and
extranodal extension. High-risk clinical features include the
presence of B symptoms, bulky mediastinal or peripheral
lymphadenopathy, extranodal extension of disease, and advanced
(stage IIIB- IV) disease. Bulky mediastinal lymphadenopathy
is designated when the ratio of the maximum
measurement of mediastinal lymphadenopathy to intrathoracic
cavity on an upright chest radiograph equals or exceeds
33%. Intermediate-risk features include localized
disease (stages I, II, and IIIA) with unfavorable features;
these cases may be treated similarly to advanced-stage
disease in some treatment protocols or treated with therapy
of intermediate intensity. Unfortunately, inconsistency in
risk categorization across cooperative group studies often
makes comparison of study outcomes challenging.
Radiation Therapy for Low-Risk HL
Considering the excellent survival rates achieved in children
and adolescents with low-risk presentations of HL with
From the Department of Oncology, Division of Cancer Survivorship, St. Jude’s Children’s
Research Hospital, Memphis, TN; Departments of Radiation Oncology and Pediatrics,
Philip Rubin Center for Cancer Survivorship, James P. Wilmot Cancer Center at University
of Rochester Medical Center, Rochester, NY.
Authors’ disclosures of potential conflicts of interest are found at the end of this article.
Address reprint requests to Melissa M. Hudson, MD, St. Jude Children’s Research
Hospital, Department of Oncology, Division of Cancer Survivorship, 262 Danny Thomas
Place, Mailstop 735, Memphis, TN 38105; email: melissa.hudson@stjude.org.
© 2012 by American Society of Clinical Oncology.
1092-9118/10/1-10