FEATURE
Drawing First Blood
We invite two experts to debate controversial
topics in hematology and health care.
Is There Still a Need for Radiation
Therapy in Hodgkin Lymphoma?
The standard treatment for
certain types of Hodgkin lymphoma is combined modality
therapy – consisting of chemotherapy followed by radiation
therapy. Recently, there has
been an increasing trend toward
treating patients with chemotherapy alone, omitting the
radiation therapy entirely.
Joseph M. Connors, MD
Joachim Yahalom, MD
Disclaimer:
The following positions were assigned
to the participants and do not
necessarily reflect ASH’s opinion, the
participants’ opinions, or what they
do in daily practice.
Agree? Disagree? We want to hear
from you! Send your thoughts and
opinions on this controversial
issue to ashclinicalnews@
hematology.org.
78
ASH Clinical News
Should this approach be adopted more widely, or should we
still be using radiotherapy in the
treatment of certain types of
Hodgkin lymphoma? In this edition of Drawing First Blood, ASH
Clinical News invited Joseph
M. Connors, MD, and Joachim
Yahalom, MD, to debate this
topic, with Dr. Connors arguing
that chemotherapy alone is the
optimal approach for treating
Hodgkin lymphoma, and Dr. Yahalom arguing that radiotherapy
is a necessary component of
treatment.
Joseph M. Connors, MD: Before we start
debating how to treat Hodgkin lymphoma, it might be best to discuss the
areas where we agree. The chemotherapy
of choice for adults with Hodgkin lymphoma of all stages is ABVD (doxorubicin
[Adriamycin], bleomycin, vinblastine,
and dacarbazine). Despite more than two
decades of attempts and many t housands
of patients studied in prospective clinical
trials, no alternative primary treatment
regimen has ever been identified that
results in a statistically significant better
eventual overall survival than ABVD.
Joachim Yahalom, MD: Right, ABVD
combined with radiation therapy is the
most effective treatment for early favorable and unfavorable disease. Adding a low
dose of 20 Gy in favorable patients with
very limited disease allows us to restrict
the amount of ABVD to two cycles. In
less-favorable patients with bulky disease,
B symptoms, or multiple involved sites,
four ABVD cycles supplemented with 30
Gy to only the involved sites is the standard
approach. This recommendation is based
on results from the German Hodgkin
Study Group (GHSG), which prospectively studied thousands of patients and
determined that both disease control and
overall survival were above 90 percent and
no interim positron emission tomography
(PET) scan was required during treatment
course with this approach. Most guidelines
in the United States and Europe regard this
as the standard treatment, and it is hard to
imagine how we can do better than that.
Dr. Connors: We are in agreement with each
other and with experts worldwide in saying
that the initial treatment of limited-stage
(low bulk stage IA or IIA) Hodgkin lymphoma should start with two cycles of ABVD.
Obviously, the number of cycles of ABVD
needed to maximize effectiveness is more extensive for advanced-stage disease (typically
six cycles). Fortunately, exposure to six cycles
of ABVD maximizes its effectiveness, while
minimizing late toxicity. At this level, it does
not threaten fertility, nor is it associated with
demonstrable increase in the risk of second
malignancies such as leukemia.
When we focus on what to do for
limited-stage disease after two cycles of
ABVD – whether it is a modest additional
amount of chemotherapy or radiation –
though, we disagree.
Dr. Yahalom: Obviously, in each stage, we
treat differently. But, if a patient has an
unfavorable profile despite being in the early
stages of disease – meaning disease is limited
to a single lymphatic site or to the upper part
of the body – then I think almost everyone
would agree that radiation therapy should be
added, at least to the site of the bulk.
Dr. Connors: Not quite, and we need to be
quite precise here because stage matters.
With advanced-stage disease, a full course
of six cycles of ABVD largely exhausts the
usefulness of the ABVD. At that point,
any definite residual lymphoma requires
potentially non–cross-resistant treatment. This is best assessed with functional
imaging, a PET scan and, if the PET scan
is positive and involved field radiation
therapy (IFRT) is feasible, radiation is the
obvious choice at this point.
When we focus on the decision point
for limited-stage Hodgkin lymphoma after
two cycles of ABVD, the relevant question when we consider removing radiation therapy from the equation becomes,
“What marginal overall toxicity is added
by two more cycles of ABVD, compared
with the potential long-term toxicity of
adding radiation?” Currently, there is no
credible evidence that just two more cycles
of ABVD makes any meaningful addition
to the risks of late or long-term toxicity. In
my opinion, one should choose radiation
over completing treatment with two final
cycles of chemotherapy if – and only if –
there is compelling justification, such as
an inadequate response to the initial two
cycles of ABVD. Fortunately, that type of
failure of the two cycles of ABVD to induce
a complete remission occurs in less than 20
percent of patients, but, when it does occur
radiation should be strongly considered.
When the optimal stage-appropriate
use of ABVD is employed, the majority of
patients with Hodgkin lymphoma do not
require the use of radiotherapy.
Dr. Yahalom: But don’t you find it worrisome that almost all of the studies questioning the utility of radiation therapy
have substituted the radiation therapy
Continued on page 80
December 2014