Radiotherapy and Oncology 79 (2006) 270–277

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Guidelines

Involved-node radiotherapy (INRT) in patients with early

Hodgkin lymphoma: Concepts and guidelines
Theodore Girinskya,*, Richard van der Maazenb, Lena Spechtc, Berthe Alemand,
Philip Poortmanse, Yolande Lievensf, Paul Meijndersg, Mithra Ghalibafiana,
Jacobus Meerwaldth, Evert Noordijki, on behalf of the EORTC-GELA Lymphoma Group
a
Department of Radiation Oncology, Institut Gustave Roussy, Villejuif, France, bDepartment of Radiotherapy, Nijmegen, The Netherlands,
c
The Finsen Centre Rigshospitalet, Copenhagen University Hospital, Denmark, dDepartment of Radiotherapy, The Netherlands Cancer
Institute, Amsterdam, The Netherlands, eDepartment of Radiotherapy, Dr Bernard Verbeeten Instituut, LA Tilburg, The Netherlands,
f
Radiotherapy Department, Leuven, Belgium, gDepartment of Radiotherapy, Antwerpen, Belgium, hDepartment of Radiation Oncology,
Medisch Spectrum Twente, Enschede, The Netherlands, iDepartment of Clinical Oncology,
Leiden University Medical Center, The Netherlands

Abstract
Background and purpose: To describe new concepts for radiation fields in patients with early stage Hodgkin lymphoma
treated with a combined modality.
Patients and materials: Patients receiving combined modality therapy with at least 2 or 3 cycles of chemotherapy prior
to radiotherapy. Pre- and postchemotherapy cervical and thoracic CT scans are mandatory and should be performed,
whenever possible, in the treatment position with the use of image fusion capabilities. A pre-chemotherapy PET scan is
strongly recommended to increase the detection of involved lymph nodes.
Results: Radiation fields are designed to irradiate the initially involved lymph nodes exclusively and to encompass their
initial volume. In some cases, radiation fields are slightly modified to avoid unnecessary irradiation of muscles or organs
at risk.
Conclusions: The concept of involved-node radiotherapy (INRT) described here is the first attempt to reduce the size of
radiation fields compared to the classic involved fields used in adult patients. Proper implementation of INRT requires
adequate training and an efficient prospective or early retrospective quality assurance program.
q 2006 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 79 (2006) 270–277.

Keywords: Hodgkin lymphoma; Involved-node radiotherapy; Involved-field radiation treatment; Combined modality treatment

Radiation treatment remains a key component in
combined modality therapy for patients with early stage
Hodgkin lymphoma. Its use has been questioned due to late
complications, which are dependent on the irradiated
volume and radiation dose [1,2,7,10,11,14].
The efficacy of radiation doses below the conventional 36–
40 Gy has gradually been demonstrated [3,4,12]. A decline in
late complications is expected with lower radiation doses as
their incidence is correlated with the amount of radiation
[5,9]. It is noteworthy that the use of smaller doses has
already been implemented by most centers and groups.
Smaller radiation fields should also lead to a decrease in late
complications as the amount of irradiated normal tissue is
reduced. Recent data seem to suggest that these assump-
tions might be correct [5,9]. With effective chemotherapy,
0167-8140/$ - see front matter q 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.radonc.2006.05.015
involved-field radiotherapy (IFRT) was shown to be sufficient
[6]. However, the definition of IFRT was not always clear, and
most often, lymph node regions were irradiated according to
the Ann Arbor staging diagram, which was not designed to
delimit radiation fields. A recent review of relapses in
patients treated with chemotherapy alone showed that most
recurrences occurred in the initially involved lymph nodes
[13]. With modern sophisticated techniques, including better
CT scan imaging, FDG-PET/CT scans and more accurate
radiation technology, it is now possible to customize
radiotherapy for each patient with accurate delivery of
radiation to the initially involved volume while minimizing
the radiation dose to normal tissues.
The concept of IFRT, which included the whole initially
involved lymph node region can now be replaced by the
 T. Girinsky et al. / Radiotherapy and Oncology 79 (2006) 270–277 271

Fig. 1. Clinical target contouring (CTV) of a cervical tumor mass in complete remission (CR) after chemotherapy. (A) Prechemotherapy axial CT
scan. (B) Contouring of the initial tumor volume (yellow color). (C) Initial tumor volume superimposed on the postchemotherapy axial CT (yellow
color). (D) Adequate CTV contouring taking into account the initial tumor volume on the postchemotherapy axial CT (green color).

concept of involved-node radiotherapy (INRT), which only
includes the initially involved lymph node(s). This new
concept of INRT will be applied in the new EORTC-GELA
randomized trial for patients with early stage Hodgkin
lymphoma. In order to achieve this, radiation guidelines
must be very clear, radiation oncologists must be
adequately trained and early retrospective or even
prospective quality assurance programs must be in place
and fully functional. The purpose of this paper is to
describe the radiation guidelines and to illustrate the
possible advantages of INRT over IFRT.
Definitions and guidelines
To successfully implement the INRT concept, a few
rules must be followed. Patients must be examined by the
radiation oncologist before chemotherapy. All patients
must have pre- and postchemotherapy cervical and
thoracic CT scans (axillary lymph node areas must be
clearly visible on thoracic CT scans). Whenever feasible,
CT scans should be performed in the treatment position
as well as the prechemotherapy PET-CT, which can help
pinpoint previously undetected involved lymph nodes.
Whenever possible, CT scans should be evaluated with a
radiologist. Moreover, CT simulation, modern radiation
techniques (such as 3D-conformal radiotherapy, IMRT or
respiratory-gated radiotherapy) and immobilization
devices are strongly recommended for proper implemen-
tation of INRT.
The remission status after chemotherapy should be
determined for each initially involved lymph node
exclusively using CT scans. Complete remission (CR)
is defined as the complete disappearance of clinically
and/or radiologically detectable disease. A CRu is defined
as at least a 75% decrease in tumor size. A partial
response (PR) is at least a 50% decrease in tumor size.
Failure is less than a 50% decrease or any increase in
tumor size.
Design of radiation fields
To achieve the best quality treatment it is strongly
recommended that pre- and postchemotherapy CT scans be
performed with patients in the treatment position. The same
rules apply to FDG-PET/CT scans. Fusion possibilities,
allowing the overlapping of the pre- and postchemotherapy
CT scans are also strongly recommended. However, they
must be used with caution owing to many assumptions
underlying such techniques.
272 Involved-node radiation therapy
Initially involved lymph nodes in CR or CRu
Cervical and axillary lymph nodes
As initially involved lymph nodes are either no longer
visible or of normal size or are in CRu, a CTV (clinical target
volume) is contoured. The CTV is the initial volume of the
lymph node(s) before chemotherapy. In other words, the
CTV incorporates the initial location and the extent of
the disease. However, normal structures that have been
displaced by the enlarged lymph node(s) are not included in
the irradiated volume (for example, a neck muscle) (Figs. 1
and 2). Whenever possible, blood vessels are not included in
the CTV if involved lymph nodes are clearly located at a
distance from them. In case of a CRu with a visible lymph
node remnant, the lymph node remnant should be included
in the CTV.
The PTV is the CTV with a margin taking into account
organ movement and set-up variations. In most situations, a
1 cm isotropic margin is considered adequate.
Fig. 2. Clinical target contouring (CTV) of a cervical tumor mass in
complete remission (CR) after chemotherapy. (A) Contouring of the
initial tumor volume (yellow color). (B) Initial tumor volume
superimposed on a coronal postchemotherapy CT scan (yellow
color). (C) Adequate CTV contouring (green color) taking into
account the initial tumor volume on a coronal postchemotherapy CT
scan.
Mediastinal area
As the mediastinal area is considered to be in complete
remission or CRu, a CTV is contoured. The CTV is the initial
volume of the mediastinal mass (in the case of a CRu, the
lymph node remnant is considered part of the CTV). In the
case of a CR, the normal mediastinum is contoured and
the CTV should not exceed the lateral mediastinal
boundaries. In the case of a CRu, the normal mediastinum
is contoured and the CTV should not exceed the lateral
mediastinal boundaries except where lymph node remnants
are still present. Whenever possible, blood vessels should be
avoided and in order to decrease lung toxicity, the length of
the CTV is the length of the mediastinal mass or lymph
node(s) before chemotherapy and the width of the CTV is
the width of the mediastinal mass or lymph node(s) after
chemotherapy (Figs. 3 and 4).
The PTV is the CTV with a margin taking into account
organ movement and set-up variations. In most situations, a
1 cm isotropic margin is considered adequate.
Initially involved lymph nodes in PR (partial
remission)
Cervical and axillary lymph nodes
As initially involved lymph nodes are in partial remission,
the GTV is the lymph node remnant(s) alone and it should be
contoured first. The CTV is the initial volume of the lymph
node(s) before chemotherapy, as described earlier. There-
fore, 2 PTVs should be outlined. The initial PTV (or PTV1) is
the CTV including the GTV (i.e. initial tumor mass and lymph
node remnant(s)) with a margin to take into account organ
movement and set-up variations. In most situations, a 1 cm
isotropic margin is considered adequate. The boost PTV (or
PTV2) is the GTV alone with a margin to take into account
organ movement and set-up variations. In most situations, a
1 cm isotropic margin is considered adequate.
Mediastinal area
As the initially involved lymph node(s) or the tumor
mass is (are) in partial remission, a GTV, which is the
lymph node remnant(s) or the remaining mass alone,
should be contoured first. The CTV is the initial volume of
the mediastinal mass (Figs. 5 and 6), as mentioned above.
Whenever possible, blood vessels and the heart should be
avoided and lung toxicity decreased. Two PTVs should be
outlined: the initial PTV (or PTV1) is the CTV including
the GTV (i.e. the initial tumor mass and the lymph node
remnant(s)) with a margin to take into account organ
movement and set-up variations. In most situations, a
1 cm isotropic margin is considered adequate. The boost
PTV (or PTV2) is the GTV alone with a margin to take into
account organ movement and set-up variations. In most
situations, a 1 cm isotropic margin is considered
adequate.
Treatment and dose prescription
The dose must be specified according to ICRU 50/62
recommendations [8] and the PTV must receive a dose
 T. Girinsky et al. / Radiotherapy and Oncology 79 (2006) 270–277 273

Fig. 3. Clinical target contouring (CTV) of a mediastinal tumor mass in an unconfirmed complete remission (CRu). (A) Contouring of the initial
tumor volume (pink color). (B) Initial tumor volume superimposed on an axial postchemotherapy CT scan (pink color). (C) Adequate CTV
contouring taking into account the initial tumor volume on an axial postchemotherapy CT scan (blue color).

Fig. 4. Clinical target contouring (CTV) of a mediastinal tumor mass in an unconfirmed complete remission (CRu). (A) Coronal prechemotherapy
CT scan of the initial tumor mass. (B) Contouring of the initial tumor volume (pink color). (C) Coronal postchemotherapy CT scan.( D) Initial
tumor volume superimposed (pink color) on a coronal postchemotherapy CT scan and tumor mass remnant contouring (green color). (E)
Adequate CTV contouring (blue color) taking into account the initial tumor volume on a coronal postchemotherapy CT scan.
274 Involved-node radiation therapy

Fig. 5. Clinical target contouring (CTV) and gross volume contouring (GTV) of a mediastinal mass in partial remission. (A) Prechemotherapy axial
CT scan. (B) Contouring of the initial tumor volume (yellow color). (C) Postchemotherapy axial CT scan. (D) Initial tumor volume superimposed
on a postchemotherapy CT scan (yellow color). (E) Adequate CTV contouring (green color) taking into account the initial tumor volume. (F)
Adequate GTV contouring (yellow color) for the radiation boost.

comprised between 95 and 107%. If the initially involved
lymph nodes are more than 5 cm apart, then separate fields
should be devised. Otherwise, the involved lymph nodes
should be included in the same radiation field.
It is strongly recommended that modern radiation
techniques such as 3D-conformal radiotherapy, intensity
modulated radiotherapy or respiratory-gated radiotherapy
should be used, notably for mediastinal tumor masses.
However, the final choice will be left to the discretion of the
physician. If a conventional treatment is used with anterior
and posterior fields, the size of the field should be at least
5!5 cm.
Radiation treatments should be delivered using five
fractions of 1.8–2 Gy per week. Portal imaging of all fields
should be performed consecutively, within the first 2 days of
treatment and once a week thereafter. Whenever feasible,
daily portal controls are recommended.
Monthly quality assurance meetings should be convened
in large cancer centers or in any local treating facilities with
all the radiation oncologists participating in the randomized
trials.
Discussion
As chemotherapy has become more efficient, extended
fields have been progressively replaced by involved fields.
This was demonstrated to be sufficient in patients with early-
stage unfavorable Hodgkin’s lymphoma by the German
Hodgkin Study Group [5] and by the EORTC-GELA cooperative
H8 trial [6]. A few years ago, the EORTC-GELA radiotherapy
group decided to further the concept of radiation field
reduction because late complications (notably cardiovascu-
lar and second cancers) were correlated with the size of
radiation fields. This led to the concept of involved node
radiotherapy (INRT) in which only initially involved lymph
nodes are irradiated. This concept has been recently
vindicated by Shahidi et al. [13] who showed that
 T. Girinsky et al. / Radiotherapy and Oncology 79 (2006) 270–277 275

Fig. 6. Clinical target contouring (CTV) and gross volume contouring (GTV) of a mediastinal mass in partial remission. (A) Prechemotherapy
coronal CT scan. (B) Contouring of the initial tumor volume (yellow color). (C) Postchemotherapy coronal CT scan. (D) Initial tumor volume
(green color) superimposed on the postchemotherapy CT scan. (E) Adequate CTV contouring taking into account the initial tumor volume (blue
color). (F) Adequate GTV contouring (yellow contouring) for the radiation boost.

Fig. 7. Comparison between dose distributions using either IFRT (A) or INRT (B) for involved cervical lymph nodes.
276 Involved-node radiation therapy
Fig. 8. Comparison between radiation field sizes and the volume of heart irradiation using either IFRT (A and B) or INRT (C and D) for a
mediastinal tumor mass (PTV in red color).
recurrences usually occurred in initially involved nodes in
patients treated with chemotherapy alone.
The design of INRT also implies that the initial tumor
volume should be irradiated. This design can be
considered as an initial requirement but not necessarily
as a final one. The decision to deliver radiation to the
initial tumor volume was based on two major facts. First,
it was considered an intermediate step between conven-
tional involved-field irradiation and far more limited
irradiation of the tumor remnants alone. Secondly, it
was realized that by delivering radiation exclusively to
tumor remnants, no radiation would be delivered to
lymph nodes in complete remission. This attitude seemed
to be premature and our decision to even deliver
radiation to lymph nodes in CR was recently vindicated
by the results of the H9 F trial [12].
It is noteworthy that gradually reducing the size of the
radiation field will provide radiation oncologists with a
transition period allowing learning and training.
The use of INRT implies greater accuracy in identifying
and contouring involved lymph nodes. Therefore, all modern
imaging technologies should be used to achieve this goal,
notably the prechemotherapy PET scan. As fusion possibi-
lities are recommended to delineate the initial tumor
volume on the postchemotherapy CT scan, all radiological
imaging should be best performed with the patient in the
treatment position.
Better sparing of normal tissues (salivary glands, heart,
coronary arteries, and breast in female patients) is expected
with the use of INRT compared with conventional IFRT
(Figs. 7 and 8) provided the initial tumor mass is not too large
and involved lymph nodes are not too numerous.
Conclusions
INRT is expected to be as good as IFRT in terms of local
control. Significantly fewer late complications are expected
because of limited irradiation of normal tissue. Training and
quality assurance programs will be crucial for the proper
implementation of INRT guidelines. More details will soon be
available on the EORTC website.
Acknowledgements
The authors thank Lorna Saint Ange for editing and La Ligue
Française contre le Cancer, Comite de Paris for financial support.
* Corresponding author. Theodore Girinsky, Department of
Radiation Oncology, Institut Gustave Roussy, 94805 Villejuif,
France. Tel.: C33 142 114759; fax: C33 142 116533. E-mail
address: girinsky@igr.fr
Received 28 April 2006; accepted 18 May 2006
 T. Girinsky et al. / Radiotherapy and Oncology 79 (2006) 270–277
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