Hodgkin's lymphoma, initially considered an inflammatory disease, is now classified as a malignant lymphoma with management evolving from radiation to combined chemotherapy and radiation approaches. It predominantly presents with painless lymphadenopathy and systemic symptoms, with diagnostic procedures including a thorough history, physical examination, and imaging studies. Prognostic factors are critical in determining therapy effectiveness, with a variety of treatment regimens available, such as the ABVD chemotherapy combination and varying radiation techniques.

1. Hodgkin Lymphoma
Dr. Dipalee B. Borade
DNB Student, Radiotherapy Dept.
Jupiter Hospital,Thane

2. Introduction
Hodgkin’s disease was initially described as an inflammatory
disease (hence the term “disease”), but is clearly
recognized and treated as a malignant lymphoma (hence the
more accurate term Hodgkin’s lymphoma (HL) is used
synonymously with Hodgkin’s disease).
The management of Hodgkin’s lymphoma has evolved from
extended-field radiation alone as the main therapy to a
combined-modality approach with
chemotherapy and radiation, or chemotherapy alone.
2

3. Epidemiology and Risk Factors
 Always begins in lymph nodes
 More than 80%- cervical lymph node >50% have mediastinal disease
 Isolated extralymphatic involvement in the absence of nodal disease is
rare
 The reported incidence is less than 3 per 100,000 and 0.56% of all cancers
 Male predominance (1.2:1)
 Rare in children <10 years of age. Median age is 26 years, Bimodal peak-
early peak 25 to 30 years and A second peak, from age 75 to 80 years

4.  A relation between HD and previous infection with Epstein-Barr
virus
(EBV4Weiss et al.5 identified components of the EBV genome in the cellular DNA of Reed–Sternberg cells
in lymph nodes involved by HD)
Mueller et al.6 identified elevated levels of immunoglobulin G and immunoglobulin A against the EBV
capsid antigen and elevated levels of antibody against the EBV nuclear antigen and early antigen D in
the serum of patients with Hodgkin lymphoma 3 to 156 months before the diagnosis of HD
 The risk more in patinets with infectious mononucleosis; Several
series demonstrated an association between EBV infection and
mixed-cellularity Hodgkin lymphoma, especially in children in
developing countries
 increased risk for Hispanics (vs.Whites), or children from
economically less developed (vs. more developed) regions, and
young adult men (vs. women)

5. Natural History and Clinical
Presentation
 Painles lymphadenopathy
 Systemic symptoms- unexplained fevers, drenching night sweats, weight loss,
generalize pruritus, fatigue, and alcohol-induced pain in tissues involved by HD
 Mediastinal mass on a routine chest radiograph
 90% of patients present with contiguous sites of involvement or Extension from
adjacent lymph nodes
 Hematogenous (liver or multiple bony sites) Involvement of the bones may cause
blastic changes, especially in the vertebrae (creating the classic “ivory vertebra”
on plain radiographs), pelvis, sternum, or ribs
 Nearly all patients with hepatic or bone marrow involvement by Hodgkin
lymphoma have extensive involvement of the spleen
 Rare- Gut-associated lymphoid tissues such as Waldeyer ring and Peyer patches,
Upper aerodigestive tract, Central nervous system, and Skin

6. B Symptoms
 There are three “B symptoms”
 One-third of patients present with one of these symptoms
 Fever- Classic waxing-and-waning Pel- Ebstein pattern
 Night sweats may be drenching and require a change of bedclothes
 Significant weight loss
 Occur even in patients with relatively limited disease (stage II) but
uncommon in stage I disease

7. Diagnostic and Staging Procedures for
Hodgkin Lymphoma
 History- Systemic B symptoms: unexplained fever, drenching night sweats,
weight loss >10% of body weight in the last 6 months Other symptoms: alcohol
intolerance, pruritus, respiratory problems, fatigue
 Physical examination- Palpable nodes (note number, size, location, shape,
consistency, mobility), Palpable viscera
 Laboratory studies- Complete blood count, differential, platelets, Erythrocyte
sedimentation rate, Serum albumin, lactate dehydrogenase, liver function
studies, Blood urea nitrogen, creatinine, Pregnancy test in women of
childbearing age
 Radiographic studies- Chest radiographs: posteroanterior and lateral; Contrast-
enhanced computed tomographic (CT ) scan of thorax, abdomen, and pelvis;
Contrast-enhanced CT scan of neck (if neck irradiation is indicated); Integrated
positron emission tomography-CT scan
 Additional biopsies, if indicated- Bone marrow, needle biopsy (if
subdiaphragmatic disease or B symptoms); Cytologic examination of effusions, if
present; Percutaneous liver biopsy if abnormal liver function tests but normal CT

8. The Ann Arbor Staging Classification for
Hodgkin’s Disease
 Stage I Involvement of a single lymph node region
 Stage II Involvement of two or more lymph node regions on the same side of
the diaphragm (II ), or localized involvement of an extralymphatic organ or site
and one or more lymph node regions on the same side of the diaphragm (IIE )
 Stage III Involvement of lymph node regions on both sides of the diaphragm
(III), which may also be accompanied by involvement of the spleen (IIIS ) or by
localized involvement of an extralymphatic organ or site (IIIE ) or by both (IIISE )
 Stage IV Diffuse or disseminated involvement of one or more extralymphatic
organs or tissues, with or without associated lymph node involvement
 The absence or presence of fever, night sweats, and/or unexplained loss of 10% or more of body weight
in the 6 month before diagnosis is denoted by the suffix letter A or B, respectively
 The Cotswolds modification of the Ann Arbor system employs the subscript “x” to designate large
mediastinal adenopathy

10. Pathologic Classification
 Reed– Sternberg cell- Binucleate, prominent centrally located nucleolus in each
nucleus, a well-demarcated nuclear membrane, and eosinophilic cytoplasm with
a perinuclear halo
 Usually account for <1%
 The majority are lymphoid cells, eosinophils, plasma cells, and other normal cells.
Reed–Sternberg cells probably originate from B-lineage cells at various stages of
development, including pre–B-cell and germinal center B-cell origin
 RS cells stain positively for CD30, PAX5, and with variable expression of the
antigranulocyte monoclonal antibody CD15
 CD20, a marker of mature B cells, may be expressed on a minority of tumor cells
(40%)
 They stain negatively with CD45, ALK, and J chain

11. World Health Organization modification of
the Lukes and Butler system
 There are five histologic subtypes of Hodgkin lymphoma
 Nodular lymphocyte predominant Hodgkin lymphoma and four
subtypes of Classic Hodgkin lymphoma: nodular sclerosis, mixed
cellularity, lymphocyte- rich, and lymphocyte-depleted
 NLPHD is characterized by
 An abundance of normal-appearing lymphocytes and a scarcity of abnormal cells
 The abnormal cells (“L and H cells” or “popcorn cells”) in nLPHD are strongly
reactive for CD20, CD45, CD79a, and PAX5 and negative for CD15 and CD30
 Young people
 Early-stage disease, usually in a solitary peripheral nodal site, and systemic
symptoms are uncommon (<10%)
 The most favorable of the histologic subtypes

12.  Classic Hodgkin lymphoma (cHD).
 The Reed– Sternberg cells in these cases are CD15+, CD30+, PAX5+, and
occasionally CD20+
 Nodular sclerosis classical Hodgkin lymphoma (NSHD) is the most
common histologic subtype
 Involved nodes often have a thickened capsule and are traversed by broad bands
of birefringent collagen that surround nodules of cells consisting of lymphocytes,
eosinophils, plasma cells, and tissue histiocytes intermixed with a variable
proportion of atypical mononuclear cells and Reed–Sternberg cells.These cells
may be in empty(lacunar) spaces, which are artifacts of formalin fixation
 The clinical presentation includes common mediastinal involvement, and one-
third of patients have B symptoms
 The natural history of NSHD is less favorable than that of nLPHD.

13.  Mixed-cellularity classic Hodgkin lymphoma (MCHD)- Diffuse effacement of
lymph nodes by lymphocytes, eosinophils, plasma cells, and relatively abundant
atypical mononuclear and Reed–Sternberg cells
 Advanced disease at presentation
 In older population
 Natural history of MCHD is less favorable than that of NSHD
 Lymphocyte-rich classic Hodgkin lymphoma (LRHD)- It usually has a nodular
growth pattern
 Early stage, absence of B symptoms, and excellent prognosis
 Lymphocyte-depleted classic Hodgkin lymphoma (LDHD)- Paucity of normal-
appearing cells and an abundance of abnormal mononuclear cells, Reed–
Sternberg cells, and Reed–Sternberg variants
 Difficult to differentiate from anaplastic large-cell lymphoma
 Uncommon subtype of HD
 Older patients, advanced disease and B symptoms
 Worst prognosis of all histologic subtypes of Hodgkin lymphoma.

14. Prognostic Factors and
Therapeutic Implications
 Highly curable
 prognostic factors are more important
for defining therapy than for predicting
outcome
 International Prognostic Score for
Advanced Hodgkin Lymphoma
 Three or more adverse risk factors- An
unfavorable prognostic group
 Patients with stage I or II disease often
have only one or two adverse factors
based on this index
 low (0–1), intermediate (2–3), or
high (4–7) risk.
Factor
Unfavorable
Covariate
Serum albumin <4 g/dL
Hemoglobin <10.5 g/dL
Sex Male
Age ≥45 yr
Stage IV (Ann Arbor)
Leukocyte count ≥15,000/mm3
Lymphocyte count
<600/mm3 or <8%
of white count

15. Treatment Groups in Early Stage
15

16. General guidelines for Hodgkin’s Lymphoma treatment
16

17. General Management
 Chemotherapy:
 With the introduction of doxorubicin (Adriamycin), completely
novel drug combinations were developed
 The most successful of these is ABVD, which includes doxorubicin,
bleomycin, vinblastine, and dacarbazine
 ABVD has replaced MOPP as the gold standard of chemotherapy
for Hodgkin lymphoma.
 This is based largely on the results of an intergroup trial that
compared MOPP, ABVD, and MOPP/ABVD.

18. Combination Chemotherapy Regimens
18

19. 19

20. 20

21.  The Milan trial was among the first and most influential in
demonstrating the high cure rate of a brief course of ABVD
(four cycles) combined with involved-field radiation therapy
in limited-stage Hodgkin’s lymphoma
 Subsequently, multiple trials have explored the questions of
how many cycles of ABVD are needed and what radiation
dose is needed to maintain these outstanding results.
21

22.  More recently, in an effort to reduce toxicity, the StanfordV regimen,
which almost always includes a component of radiation, was developed
as an alternative to ABVD
 The German Hodgkin Study Group (GHSG) developed the BEACOPP
regimen, which may be administered in a baseline, escalated, or 14-day
schedules
 Most recently, a completely new systemic agent has been approved by
the FDA for the treatment of Hodgkin lymphoma. Brentuximab vedotin
(BV) is an anti-CD30 monoclonal antibody linked to an antitubulin agent.
 BV has demonstrated efficacy in CD30+ lymphomas, including Hodgkin
lymphoma and anaplastic large-cell lymphoma.
 It is approved for patients who have had disease recurrence after stem
cell transplantation and is being introduced in clinical trials

23.  Among favorable patients without risk factors, the GHSG
evaluated two versus four cycles of ABVD and 20 versus
30 Gy involved-field irradiation.
 The final results of this trial have not been published, but
multiple presentations of the data to date have shown FFP
rates in excess of 95% for all four treatment arms.
 Thus, for the approximately 35% of limited-stage patients
with very favorable presentations, as few as two cycles of
chemotherapy combined with low-dose involved-field
irradiation is sufficient for cure.
23

24.  For patients with unfavorable, limited-stage Hodgkin’s
The H9U trial conducted by the EORTC-GELA
demonstrated that the less toxic ABVD regimen was as
effective as the BEACOPP regimen and that four cycles of
treatment were sufficient.
Similarly, the GHSG HD11 trial has shown no differences
in outcome thus far between ABVD and BEACOPP in
limited-stage patients with risk factors.
24

25. Randomized ClinicalTrials in
Limited-Stage Hodgkin’s Lymphoma
25

26. 26
26

27. The early CALGB study determined that ABVD-containing
combinations were superior.
A second U.S. Intergroup trial comparing ABVD to the
hybrid MOPP/ABV combination, concluded that the
treatments were similarly efficacious but ABVD was less
toxic.
On the basis of these trials, ABVD was widely adopted as
the standard chemotherapy for advanced Hodgkin’s
lymphoma with an expected cure rate of about 70%.
27

28. Randomized ClinicalTrials in
Advanced-Stage Hodgkin’s Lymphoma
28

29. 29

30. RadiationTherapy
 The principal to treat involved nodes and regions at high risk for
containing disease to a dose associated with a high likelihood of tumor
eradication
 This requires thoughtful evaluation of all imaging studies, especially
diagnostic CT and integrated PET-CT scans
 A precise simulation with appropriate immobilization
 Consideration of organ motion
 Detailed treatment planning, and effective treatment delivery, including
portal imaging and appropriate quality assurance measures

31.  Three-dimensional conformal treatment planning and
opposed-field treatment is appropriate
 Occasionally intensity-modulated radiation therapy
(IMRT)- Better dose conformality, improved dose–
volume histogram (DVH) criteria for the heart,
coronary arteries, esophagus, and lungs and less
acute toxicity
 At the expense of the low-dose “bath,” which may put
larger volumes of normal tissue at risk for the
development of secondary cancer, for example, the
lungs, breasts (in women), and thyroid gland
 Useful in situations of reirradiation

32.  In the uncommon situations when radiation therapy
alone is used for the treatment of Hodgkin
lymphoma (primarily for nLPHD), the National
Cancer Center Network (NCCN) guidelines
recommend a dose of 30 to 36 Gy to involved and 25
to 30 Gy to uninvolved regions
 Fractions of 1.5 to 1.8 Gy depending on field size and
patient tolerance
 More commonly, radiation therapy is used in the
combined-modality setting
 The NCCN guidelines is- 20 to 30 Gy for nonbulky
and 30 to 36 Gy for bulky sites of disease

33.  The classic fields for lymphoma by radiotherapy
alone included the mantle and inverted-Y
 Clinical trials have demonstrated an equivalence of
“involved-field” treatment (IFRT) with “extended-
field” or “subtotal-lymphoid” irradiation in the
context of combined-modality therapy programs
 Involved field irradiation has been adopted as the
standard for combined-modality therapy
 More recent trials- application of “involved-node
radiotherapy” (INRT) or “involved-region” or
“involved-site” irradiation

34. PET-CT “Simulation”
 Integrated PET-CT- Part of the initial staging for all patients
 Accurate information of the initial extent of disease
 However, not usually obtained in the treatment position or on a flat
couch
 PET-CT scan is usually repeated After the completion of chemotherapy
 After the radiation therapy simulation, the data from the initial staging
PET-CT is merged with it in order to localize the initial sites of disease.
 The accuracy of the registration will vary, depending on patient
positioning for the two studies
 This needs to be accounted for ultimate design of the treatment fields.

35. Supradiaphragmatic Fields
 The classic mantle included all of the major lymph node regions above
the diaphragm
 The field extended from the inferior portion of the mandible almost to
the level of the insertion of the diaphragm
 With individually contoured lung blocks and conformed to the patient’s
anatomy and tumor localization.
 In addition to the lung blocks, blocks could be placed over the occipital
region and spinal cord posteriorly, the larynx anteriorly, and the humeral
heads both anteriorly and posteriorly.
 The use of these blocks depended on total dose planned and proximity of
the adenopathy.

36. Modified involved Field Involved site RT

37. 37
Classic two-dimensional Mantle field
 Set up supine, with the head fully extended
 The superior margin- bisect the mandible and passed through the mastoid
process
 The lateral margins- flash the axillae (with humeral head blocks if the arms were
at sides)
 The inferior axillary margins- level of the inferior tips of the scapulae
 The inferior mediastinal border- at the level of theT10-11 interspace
 The lung blocks- to provide 1-cm margin around the mediastinal contours and∼
also encompass the pulmonary hilar lymph nodes
 The superior most point of the lung blocks was no higher than the inferior tip of
the head of the clavicle with the tops of the lung blocks tapered laterally, often
parallel to the projection of a posterior rib, in order to expose the high
axillary/infraclavicular lymph nodes.

38. LYMPH NODAL REGIONS
Lymph Nodal
Groups
38

39. Radiotherapy Fields
39

40. 40

41. Fields for I F RT
41

42. Unilateral Cervical/Supraclavicular Region
Arms position: Akimbo or at sides
Upper Border: 1 to 2 cm above the
lower tip of the mastoid process and
midpoint through the chin.
Lower Border: 2 cm below the bottom
of the clavicle.
Lateral Border:To include the medial
two-thirds of the clavicle.
42

43. Medial Border:
(a) If the SCL nodes are not involved, the
border is placed at the ipsilateral transverse processes
except when medial nodes close to the vertebral bodies are
seen on the initial staging neck CT scan. For medial nodes
the entire vertebral body is included.
(b)When the SCL nodes are involved, the
border should be placed at the contralateral transverse
processes
43

44. Blocks:
A posterior cervical cord block is required only if
cord dose exceeds 40 Gy.
Mid-neck calculations should be performed to
determine the maximum cord dose, especially
when the central axis is in the mediastinum.
A laryngeal block should be used unless lymph nodes
were present in that location. In that case the block should
be added at 20 Gy.
44

45. 45
Bilateral Cervical/Supraclavicular Region
Both cervical and SCL regions should
be treated as described in the
preceding slide regardless of the
extent of disease on each side.
Posterior cervical cord and larynx
blocks should be used.
45

46. Mediastinum
Arms position: Akimbo or at sides.The arms-up position is
optional if the axillary nodes are involved.
Upper Border: C5-6 interspace. If SCL nodes are also
involved, the upper border should be placed
at the top of the larynx.
46

47. Lower Border:The lower of: (a) 5 cm below the carina
or (b) 2 cm below the pre-chemotherapy
inferior border.
Lateral Border:The post-chemotherapy volume with
1.5-2 cm margin.
Hilar Area:To be included with 1 cm margin unless
initially involved, in which case the margin
should be 1.5 cm.
47

48. Axillary Region
Arms position: Arms akimbo or arms up.
Upper Border: C5-6 interspace.
Lower Border:The lower of the two: (a) the tip of the
scapula or (b) 2 cm below the lowest axillary node.
Medial Border: Ipsilateral cervical transverse process.
Include the vertebral bodies only if the SCL are involved.
Lateral Border: Flash axilla.
48

49. 49

50. Abdomen (Para-Aortic Nodes)
Upper Border:Top ofT11 and at least 2 cm above
pre-chemotherapy volume.
Lower Border: Bottom of L4 and at least 2 cm below
pre-chemotherapy volume.
Lateral Borders:The edge of the transverse processes and
at least 2 cm from the
post-chemotherapy volume.
50

51. Example of a para-aortic–
spleen field treated with
respiratory gating. In this
example there was a positron
emission tomography+ node at
the L1 level, and the inferior
portion of the para-aortic field
was set at the bottom of L2.
The para-aortic nodes are
highlighted
in light red and the spleen in
dark red. Due to the complex
shape of this field, it is
defined with a combination of
multileaf collimators and
Cerrobend blocks (shown in
light
orange) to shield the base of
the left lung and the upper half
of the left kidney.

52. Inguinal/Femoral/External Iliac Region
Upper Border: Middle of the sacroiliac joint.
Lower Border: 5 cm below the lesser trochanter.
Lateral Border: The greater trochanter and 2 cm lateral to
initially involved nodes.
52

53. Medial Border: Medial border of the obturator foramen
with at least 2 cm medial to involved nodes.
If common iliac nodes are involved the field
should extend to the L4-5 interspace and
at least 2 cm above the initially involved
nodal border.
53

54. 54

55. Mantle
bilateral cervical,
SCV, infraclavicular,
mediastinal, hilar,
and axilla
Mini-mantle:
mantle without
mediastinum, hila
Modified mantle:
mantle without axilla
55
mini mantle modified mantle

56. Mantle Field

57. Simulate with
Arms - up (to pull axillary LN from chest to allow for
more lung blocking) or
Arms akimbo (to shield humeral heads and minimize
tissue in SCV folds)
Head extended
this ensures the exclusion of the oral cavity and
teeth from the RT fields, and decreases the dose to the
mandible
57

58. Borders: Lateral = beyond humeral heads;
Inferior = bottom of diaphragm (T11/12);
Superior = inferior mandible
Blocks: Larynx on AP field
Humeral heads on AP and PA fields
PA cord block (if dose >40 Gy)
Lung block at top of fourth rib to cover IC LN
If pericardial or mediastinal extension, include
entire heart to 15 Gy, then block apex of heart. After
30 Gy, block heart beyond 5 cm inferior to carina
(unless residual disease)
58

59. Inverted Y Field

60. 60
STLI
TLI

61.  With 3D treatment planning, the initially involved lymph nodes (gross
tumor volume [GTV]) and adjacent “at-risk” lymph nodes (clinical target
volume [CTV]) are outlined on cross-sectional images, and field design is
completed to ensure a dose range of 95% to 105% of the prescribed dose
to the planning target volume (PTV)
 The CTV will generally extend 2 to 5 cm proximal and distal to initial PET-
or CT-positive disease.The PTV expansion is then 1 cm∼
 Although special techniques such as deep inspiration breath hold, active
breathing control, and respiratory gating are infrequently used in
treatment of Hodgkin lymphoma
 They do demonstrate improvements in DVH criteria for the lungs and
heart - useful in the setting of treatment for patients with large
mediastinal masses.

62. Reference :

63. Volume Definitions for Planning Radiation
Therapy for Lymphoma
 These principles apply whether Involved Site Radiation
Therapy (ISRT) or Involved Node RadiationTherapy (INRT) is
applied
 The difference between them is the quality and accuracy of
the pre chemotherapy imaging
 Determine the margins needed to allow for uncertainties in
the contouring of the CTV

64. Volume of interest acquisition
 3-dimensional (3D) simulation study using
 CT simulator
 PET/CT simulator
 Magnetic resonance imaging simulator
 Imaging studies should be obtained with the patient in the
treatment position and using the planned immobilization
devices

65. Determination of GrossTumorVolume
 Pre chemotherapy (or pre surgery) GTV
 No chemotherapy or post chemotherapy GTV

66. Determination of ClinicalTargetVolume
 The CTV encompasses the original (before any intervention)
GTV
 Normal structures such as lungs, kidneys, and muscles that
were clearly uninvolved should be excluded from the CTV
based on clinical judgment
 The following points should be considered:
▪ Quality and accuracy of imaging
▪ Concerns of changes in volume since imaging
▪ Spread patterns of the disease
▪ Potential subclinical involvement
▪ Adjacent organs constraints

67.  If separate nodal volumes are involved, they can potentially
be encompassed in the same CTV
 If the involved nodes are more than 5 cm apart, they can be
treated with separate fields using the CTV-to-PTV expansion
guidelines

68. Determination of InternalTargetVolume
 CTV plus a margin taking into account uncertainties in size,
shape, and position of the CTV within the patient
 ITV is mostly relevant when the target is moving, most
commonly in the chest and upper abdomen with respiratory
movements
 ITV is calculated by :
 4D CT simulation
 Fluoroscopy
 Estimated by an experienced clinician

69.  In chest or upper abdomen: Margins of 1.5 to 2 cm in the
superior-inferior direction
 In sites that are unlikely to change shape or position during
or between treatments : Outlining the ITV is not required

70. Determination of PlanningTargetVolume
 Volume that takes into account the
 CTV (or ITV, when relevant) and
 accounts for setup uncertainties in patient positioning and
alignment of the beams during treatment planning and through
all treatment sessions
 PTV margins are based on :
 Institutional protocols
 Site of area being treated with the amount of setup
uncertainties expected

71. Determination of Organs At Risk
 The organs at risk (OARs) are critical normal structures that,
if irradiated, could experience significant morbidity and
might influence treatment planning or the prescribed dose
 They should be outlined on the simulation study
 Dose volume histograms (DVH) and normal tissue
complication probability (NTCP) should be calculated

72. RadiationTherapy Dose Considerations
 Early-stage classic HL in CR after chemotherapy
 Dose to the CTV :
 Determined on the basis of the results of the German Hodgkin
Studies HD 10 and 11
 Favourable characteristics : 20 Gy in 10 fractions
 Unfavourable characteristics : 30 Gy in 15 fractions

73. Early-stage LPHL :
30 to 35 Gy in 1.8 to 2 Gy per fraction is the recommended dose
to the CTV
No advantage has been shown for higher doses
Residual lymphoma after chemotherapy :
36 to 40 Gy in 18 to 20 fractions

74. Treatment techniques
 In some situations, conventional AP-PA techniques may be
preferred
 In other situations, more conformal techniques such as IMRT,
arc therapy, or tomotherapy may offer significantly better
sparing of critical normal structures
 Recommendations as to which technique to use in
the individual case cannot be made
 Careful consideration must be given to choosing the
technique to offer the minimum risk of significant late
toxicity for that patient with adequate coverage of the
targets

77. Involved Site RadiationTherapy in
Early-Stage HL
 The concept of ISRT was developed on the basis of the INRT
concept
 ISRT accommodates cases in which optimal pre
chemotherapy imaging is not available
 It is not possible to reduce the CTV to the same extent as
with INRT because the pre chemotherapy GTV information
may not be optimal
 In ISRT, clinical judgment in conjunction with the best
available imaging is used to contour a larger CTV that will
accommodate the uncertainties in defining the pre
chemotherapy GTV

78.  If pre chemotherapy imaging is available, but image fusion
with the post chemotherapy planning CT scan is not possible
To contour the pre chemotherapy target volume on the
planning CT scan
 Allowance should be made for the uncertainty of the
contouring and differences in positioning by including a
larger volume in the CTV

79.  If no pre chemotherapy imaging is available
 To gather description of :
 The pre chemotherapy physical examination of the patient
 The location of scars and scar tissue on the post chemotherapy
planning CT scan
 The patient’s and the family’s recollections of the location of the
presenting lymph node(s)
 The CTV should be contoured taking into account all of this
information, making generous allowance for the many
uncertainties in the process

80. Involved-Node/Involved-Site Radiotherapy
 Combined-modality therapy and the recognition that late effects may be
reduced by using smaller radiation fields, and the introduction of sensitive
functional imaging techniques- helped to reduce radiation field size
 INRT requires prechemotherapy diagnostic CT and PET-CT imaging with the
patient in the treatment position, postchemotherapy contrast-enhanced CT
simulation, and fusion of the prechemotherapy and postchemotherapy images
 The fields are designed to treat only the initially involved nodes with modification
to avoid OARs
 This GTV then becomes the CTV, and a 1-cm expansion of the CTV defines the
PTV
 It may be risky – when the pretreatment PET-CT scan was not done in the
treatment position, there is poor registration between scans, or the CT
simulation scan was done without intravenous contrast
 So the concept of involved-site” irradiation is introduced

81. 81
Involved Node RadiationTherapy in
Early-Stage Classic HL
 The concept of INRT for early-stage classic HL was
developed and implemented by the EORTC
 Reduces the treated volume to a minimum, but to be safe
limit
 Optimal imaging both before and after chemotherapy is
needed
 PET/CT is the most accurate imaging method for
determining disease extent in HL, and thus up-front PET/CT
is mandatory for INRT design

82.  The pre chemotherapy PET/CT scan should be acquired with
the patient in the treatment position and using the same
breathing instructions that will be used later for RT
 After the completion of chemotherapy, a response
assessment using PET/CT or contrast-enhanced CT should be
performed
 INRT should be commenced 3 to 4 week after the
completion of chemotherapy

83.  The contouring process is as follows:
 1.The CT images of the pre chemotherapy PET/CT are used
to delineate the initially involved lymphoma volume, the
GTV-CT as determined by morphology on CT

84.  2.The PET images of the pre chemotherapy PET/CT are used
to delineate the initially involved lymphoma volume, the
GTV-PET as determined by FDG uptake

85.  3.The pre chemotherapy PET/CT is fused with the post
chemotherapy planning CT scan, and the GTV-CT and GTV-
PET are imported to the planning CT images

86.  4.The post chemotherapy tissue volume, which contained
the initially involved lymphoma tissue, is contoured using
information from both pre chemotherapy PET and pre
chemotherapy CT, taking into account tumor shrinkage and
other anatomic changes.

87.  The CTV
 Encompasses all of the initial lymphoma volume
 Still respecting normal structures that were never involved by
lymphoma, such as lungs, chest wall, muscles, and mediastinal
normal structures

88. Irradiation of Residual Mass After Full
Chemotherapy for Advanced Disease
 Advanced disease (classic HL and LPHL)
 Many centres treat patients with chemotherapy alone
(especially in the absence of bulky disease)
 Only if a CR is not achieved will RT is used
 Target in this situation is the residual mass (GTV) after
chemotherapy

89. Irradiation of Early-Stage LPHL
 When RT is used as the only treatment modality, the CTV
must be designed to encompass suspected subclinical
disease
 No advantage has been demonstrated with EFRT as opposed
to more limited treatment fields
 CTV should incorporate the GTV and include as a minimum
adjacent lymph nodes in that site and a generous margin
dictated by the clinical situation

90. Larger Field RT
 Role of larger field RT is now limited essentially to salvage
treatment in patients in whom chemotherapy is unsuccessful
and who are unable to embark on more intensive salvage
treatment schedules
 Usually addressed on a case-to-case basis and it is not
feasible to produce guidelines
 No data to support the use of extended fields that can cause
toxicity and compromise the safety of subsequent therapy
such as stem cell transplantation

91. Refractory and Relapsed HL
 Salvage RT
 Important role in local control for patients who have
primary refractory disease dominated by a local site
 Important for patients who experience relapse after
achieving a CR with initial therapy
 RT should also be considered as a salvage option in the
setting of ASCT failure, after relapse, or after progression

92.  Salvage RT yields high response rates and high local control
rates in refractory and relapsed HL and in relapses after
ASCT
 Systemic failures remain the commonest problem in this
setting, underlining the need for improved systemic therapy
in combination with salvage RT

93. Organs at Risk
 The dose range used for Hodgkin lymphoma (20 to 36 Gy) is
below the threshold tolerance for many organs, including the
spinal cord
 However, intrathoracic structures may be affected by these
doses, and careful review of DVH is warranted to minimize
both acute and late effects
 The risk for pneumonitis is related to volume of lung
irradiated, total dose, and fraction size
 The relationship between mean lung dose or Vx and
pneumonitis is complex and may vary for different diseases
and depend on patient age, smoking history, presence of
intercurrent disease, prior chemotherapy, prior surgery

94. 94
 The likelihood of radiation-related pulmonary complications
may be increased by the use of bleomycin
 A guideline followed at Stanford is not to exceed a mean lung
dose of 15 Gy after treatment with ABVD or 17 Gy after
treatment with StanfordV, treating with 1.5-Gy fractions
 When followed, the risk for radiation pneumonitis is
negligible
 Data indicate that lung cancer risk may be increased after
doses as low as 5 Gy, it is reasonable to define the lung V5
and try to minimize it

95.  The criteria for cardiac dose tolerance are not well defined; tolerances
will be affected by comorbidities, family history, and prior treatment
with cardiotoxic drugs such as doxorubicin
 Acute effects (pericarditis) - keeping the mean pericardial dose to <26 to
27 Gy and the V30 to <46%; Data for late cardiac events are less reliable
 Treatment techniques such as IMRT may succeed in reducing the cardiac
dose but increase the V5 to the lungs or V4 to the breasts, resulting in a
higher risk for secondary cancer in those organs
 The excess risk of secondary breast cancer that exists for doses as low as
4 Gy, it is reasonable to track the breast V4 and keep that volume as small
as possible, especially for women <30 years of age

96. 96
Color-wash dose distributions
for three different plans for
treating mediastinal Hodgkin
lymphoma: axial sections (top)
and sagittal
sections (bottom) for
conventional photon three-
dimensional conformal
anteroposterior/posteroanterior
fields (left), intensity-modulated
radiation
therapy photon (middle), and
anterior proton field (right).
Green outline, esophagus; red
outline, heart; pink outline,
breasts; blue outline, clinical
target volume.

97. Gonadal toxicity
 Ovaries normally overlie the iliac lymph nodes.To avoid
irradiation-induced amenorrhea, an oophoropexy must be
performed. Medial or lateral transposition of the ovaries via
laparoscopy
 Radiopaque sutures or clips over ovaries and relocate them
medially and as low as possible behind the uterine body
 A double-thickness (10 halfvalue layers) midline block is then used;
its location is guided by the position of the opacified nodes and
transposed ovaries
 When the ovaries are at least 2 cm from the edge of this block, the
dose is decreased to 8% of that delivered to the iliac nodes

98. 98
 In men, if no special blocking is provided for the testes, the
testicular dose may be as high as 10% of the dose delivered to the
inguinal-femoral nodes
 Use of a double-thickness midline block and a specially
constructed testicular shield can reduce this dose to 0.75% to
3.0%, most of which results from internal scatter.The precise dose
depends on the position of the testes in relation to the inferior
margin of the inguinal-femoral field

99. Typical
anteroposterior/posteroanterio
r field for treating unilateral
pelvic
nodes, in this case for a 34-
year-old man with stage IIA
lymphocyte-predominant
Hodgkin
lymphoma.T he initial positron
emission tomography+ nodes
are shown in blue.T he field
includes margins of at least 2
cm medial and lateral to the
nodes and a field width of at
least
6 cm.

100. Proton BeamTherapy
 The potential dosimetric advantage of treatment with protons, as
opposed to photons is well established
 The use of proton beam therapy can be associated with decreased
dose to the gut, bone marrow, and other organs
 Especially advantageous with respect to mediastinal treatment

101.  Conventional 3DCRT with opposed fields minimizes lung
exposure, but portions of the heart, especially the coronary
arteries and valves, as well as of the esophagus, cannot be spared
 IMRT plans can be quite conformal and spare those structures but
at the expense of a low-dose “bath”
 With proton there can be maximal sparing of the esophagus,
lungs, and cardiac subunits, thereby minimizing risk to those
organs, while at the same time avoiding low-dose exposure to the
breasts and lungs

102. 102
Advanced disease
 A general conclusion regarding the role of combined-modality therapy compared
with chemotherapy alone for patients with stage III to IV disease
 Patients who achieve a complete response to a full course of conventional
chemotherapy have no proven benefit from the addition of chemotherapy
 Nevertheless, irradiation is often added to such programs on a selected basis,
especially for bulky disease
 In addition, programs of attenuated chemotherapy may realize a benefit from
the addition of irradiation
 Patients who achieve only a partial response to chemotherapy may have an
improved outcome by the addition of irradiation
 Ultimately, improved imaging and evaluation of early response to chemotherapy
with FDG-PET imaging may help to identify a subset of patients who would truly
benefit from consolidative irradiation

103. Pediatric Patients
 Most contemporary programs for the management of pediatric
Hodgkin lymphoma are based on clinical staging and use
chemotherapy alone or combined-modality therapy with low dose
irradiation
 Because higher doses of irradiation are associated with
unacceptable risks for growth impairment and late effects
 To limit growth effects, irradiation doses should not exceed 15 to
25 Gy
 Children treated with these programs, all stages combined, are
reported to achieve 5-year OS rates of approximately 90% and
relapse-free rates of at least 80%

104. Older Adult Patients
 The treatment of Hodgkin lymphoma in older patients (>60 years) also poses a
challenge
 They often have less favorable histology, worse performance status, intercurrent
disease compromising the aggressive management programs used for younger
people
 Chemotherapy programs may often be modified to minimize cardiac or
pulmonary toxicity, and the hematologic reserve in elderly patients more often
results in dose reductions or premature discontinuation compared with younger
patients
 Drug combinations that seem to be more tolerable for older adults include
ChlVPP procarbazine, Alkeran, and vinblastine, and vinblastine, bleomycin, and
methotrexate (used primarily for stage I to II)
 With respect to the radiation therapy, patients may need to be treated with
slower fractionation programs and observed carefully for signs of weight loss or
general decline in performance status
 Extended fields are more difficult to tolerate than more limited fields.

105. Treatment for Relapse
 Treatment for relapse must be individualized; Initial disease
characteristics, initial treatment and response duration, relapse sites,
and general patient status must be considered
 In general, patients who were treated initially with irradiation alone for
stage I to II disease (now a relatively infrequent occurrence) should
receive chemotherapy as the primary salvage treatment
 The efficacy of combination chemotherapy in this setting is similar to
that achieved when chemotherapy is used in the primary management
of advanced disease (rate of long-term freedom from relapse of 60% or
better)
 The role of irradiation in combination with salvage chemotherapy has
not been defined but is quite reasonable to consider if relapse is in a
previously unirradiated site

106.  Patients who present initially with stage I to II disease and are treated with
chemotherapy alone, In these patients, relapse may be restricted to initial
sites of disease and be quite limited.
 It is possible that in this situation programs using irradiation alone, or at
least emphasizing the use of radiation, may be safe and effective
 For patients who present initially with stage III to IV disease and relapse
after achieving a complete response to chemotherapy or combined-
modality therapy, the standard salvage therapy is high-dose chemotherapy
with autologous hematopoietic cell rescue.
 The long-term PFS rate for these patients is expected to be approximately
50%
 Favorable prognostic factors in this group include a longer duration of
response to primary therapy and absence of extranodal disease
 Allotransplantation is not used often for relapsed Hodgkin lymphoma but
may be considered in situations of an unsuccessful autotransplant.
 Reduced-intensity conditioning regimens appear to be safer than
myeloablative regimens

107. The Role of RadiationTherapy in Hematopoietic
CellTransplantation
 Radiation therapy may be incorporated into high-dose therapy programs
such as IFRT,TLI, or total-body irradiation (TBI)
 FractionatedTBI is incorporated into a number of transplantation
programs.
 TBI is probably not the most efficacious way to use irradiation in these
patients.
 Recurrent Hodgkin lymphoma is often a locoregional problem rather
than a systemic one.
 In addition, data suggest that irradiation doses in the range used inTBI
programs (12 to 15 Gy) are likely to eradicate disease in only about 20%
of treated sites.
 It is more logical to limit irradiation to sites of failure or those at high risk
for disease, that is, initial sites of disease, especially bulky sites.

108.  At Memorial Sloan-Kettering Cancer Center, an intensive
program that incorporates pretransplantTLI has been used
 Patients who had not received previous irradiation were
treated with IFRT to 18 Gy andTLI to 18 Gy (both with twice-
daily fractionation)
 Patients who had prior irradiation were treated with IFRT
only, if organ tolerance would not be exceeded, to a dose of
18 to 36 Gy in 5 to 10 days (twice-daily fractionation),
depending on the prior doses received by the involved sites
 The 10-year OS was 56%, and EFS was 56

109. Follow-Up
 Follow-up is important to monitor for complications of therapy
and late effects and to ensure health maintenance
 As a rule of thumb, all studies that initially gave abnormal results
(e.g., chest radiograph, CT scan, PET scan) should be repeated at
the time of completion of therapy to document the completeness
of response
 The subsequent follow-up interval is typically every 2 to 4 months
during the first 2 years, every 4 to 6 months during the third and
fourth years, and annually thereafter.

110.  The most important component of follow-up is an interim history and
physical examination
 The frequency with which imaging studies should be repeated after the
completion of therapy is not well defined
 The value of more extensive imaging evaluation in the absence of
symptoms or abnormalities is questionable.
 The ESR, serum albumin, or other serum marker studies may be followed
if these markers were abnormal at presentation
 Serum thyroxine (T4) and sensitive thyroid-stimulating hormone (TSH)
levels should be obtained at least annually in patients who received
irradiation to the neck, to detect subclinical hypothyroidism

111.  In almost every case, the first episode of relapse should be
documented by biopsy
 Inflammatory disease, progressive transformation of germinal
centers, or the rebound growth of the thymus in young patients
are other reactive processes that can be confused with recurrent
Hodgkin lymphoma. All of these processes may be FDG-avid on
PET scanning.
 A challenging problem in follow-up evaluation in the past was the
interpretation of residual mediastinal abnormality on chest
radiograph or chest CT scan. However, this problem has been
obviated by the introduction of FDG-PET scanning as a
posttreatment assessment tool

112. Conclusion
 The newly defined fields of ISRT represent a significant
reduction in the volume included in the previously used IFRT
 Radiation oncologists treating HL should be involved as part
of the multidisciplinary team in the initial management plan
and attempt to introduce imaging procedures up front
before the initiation of chemotherapy
 Integrated multidisciplinary approach will enable the
optimal outcome for patients with HL

113. Conclusion
 Modern RT for HL is a highly individualized treatment
restricted to limited treatment volumes
 Modern imaging and RT techniques should be used to limit
the amount of normal tissue being irradiated, thus
minimizing the risk of long-term complications