Radiotherapy planning in lymphoma

1. RADIOTHERAPY PLANNING
TECHNIQUES IN LYMPHOMA
PRESENTER: DR.MOUMITA PAUL
PGT 2ND YEAR
Dept of Radiation Oncology
Dr. B. Borooah Cancer Institute
Guwahati-16

2. Introduction
• LYMPHOMA is a heterogeneous group of lymphoid
neoplasm that originate from lymphoid organs.
• Main types :
• 1) Hodgkin’s lymphoma
• 2) Non Hodgkin’s lymphoma
# B-cell lymphoma
# T-cell lymphoma

3. Hodgkin’s lymphoma
• Definition: A neoplastic transformation of
lymphocytes particularly in lymph nodes.
• Characterised by :
1) the presence of Reed-Sternberg cells on histology
2) Spreading in an orderly fashion in contiguous lymph
nodes

4. Hodgkin’s lymphoma
• 1)Nodular lymphocyte predominance Hodgkin’s
lymphoma
• 2)Classical Hodgkin’s lymphoma
 Nodular sclerosis Hodgkin’s lymphoma(60-80% -- M/C
mediastinal HL)
 Lymphocyte-rich classical Hodgkin’s lymphoma(5% -- best
prognosis)
 Mixed cellularity Hodgkin’s lymphoma(15-30%-- M/C in
India)
 Lymphocyte depleted Hodgkin’s lymphoma(<1%-- worst
prognosis)

5. The Ann Arbor/Cotswolds staging classification
for Hodgkin Lymphoma and Non-Hodgkin
Lymphoma

7. Non-Hodgkin Lymphoma
• Non-Hodgkin lymphomas(NHL) are heterogeneous
group of malignancies of the lymphoid system
characterised by an abnormal clonal proliferation of
B-cells, T-cells, or both.

8. Histologic classification of NHL
• 1. Low grade
a)Small lymphocytic cell
b)Follicular, predominantly small cleaved cell
c)Follicular mixed, small cleaved and large cell
• 2. Intermediate grade
a)Follicular,predominantly large cell
b)Diffuse small cleaved cell
c)Diffuse, mixed, small and large cell
d)Diffuse large cell
• High grade
a)Large cell immunoblastic
b)Lymphoblastic
c)Small noncleaved cell : Burkitt’s

9. REAL(Revised European-American
Lymphoma/-WHO classification of NHL
• Precursor B- or T-cell lymphomas
• Peripheral B- or T- cell lymphomas

10. • Precursor B-cell lymphomas
--- acue lymphoblastic leukemia
--- lymphoblastic lymphoma
• Peripheral B-cell lymphomas
--- Chronic lymphocytic leukemia/lymphocytic lymphoma
--- Chronic prolymphocytic leukemia
---Immunocytoma/lymphoplasmacytic lymphoma
--- Mantle cell lymphoma
--- Marginal zone lymphoma/ MALT-type
--- Hairy cell leukemia
--- Follicle centre cell lymphoma
--- Plasma cell myeloma/Plasmacytoma
---Diffuse large B-cell lymphoma
--- Burkitt’s lymphoma
--- Splenic marginal zone B-cell lymphoma

11. • Precursor T-cell lymphoma
--- Acute lymphoblastic leukemia
---Lymphoblastic lymphoma
• Peripheral T-cell lymphoma
---T-cell chronic lymphocytic leukemia
--- T-cell chronic prolymphocytic leukemia
--- Large granular lymphocytic leukemia
---Mycosis fungoides/ Sezary syndrome
--- Peripheral T-cell lymphoma, unspecified
--- Angioimmunoblastic T-cell lymphoma
--- Angiocentric lymphoma
--- Intestinal T-cell lymphoma
--- Adult T-cell lymphoma/leukemia
---Anaplastic large cell lymphoma

13. Indications of RT in lymphoma
• Early stage lymphoma – disease limited to one side
of the diaphragm
• Advanced-stage lymphoma – disseminated disease,
but with sites that are bulky, extended to bone sites,
and/or did not respond well to chemotherapy

14. RT alone
• Low-grade lymphoma (or indolent lymphoma)
-- Follicular lymphoma
-- Marginal zone lymphoma or MALT lymphoma
• Nodular lymphocyte predominant Hodgin’s
lymphoma(NLPHL)
Combined CT and RT
• Classical Hodgkin’s lymphoma
• Intermediate/high-grade lymphoma (or aggressive
lymphoma)
-- Diffuse large B-cell lymphoma

15. HL : Doses of RT
• Evolved from 40-44 Gy over 4-5 weeks to now 20-30
Gy over 2-3 weeks
• Candidates for 20 Gy over 2 weeks :
-- Low risk, early stage : only 1-2 sites, <10 cm, no B-
symptoms, normal ESR
-- Complete response to chemotherapy

16. NHL : Doses of RT
• Depends on type of lymphoma
--- Lower doses for indolent lymphoma
• If given with chemotherapy, depends on response to chemotherapy
--- Lower doses needed if complete response
• From 4 Gy given over 2 days to >50 Gy over 5-6 weeks.
• Candidates for 4 Gy over 2 days –
-- Advanced stage or recurrent/refractory indolent lymphoma(follicular
lymphoma, marginal zone lymphoma, mantle cell lymphoma,
CLL/SLL, cutaneous lymphoma) with local symptomatic sites
-- May especially benefit patients involvement of sites where
conventional dose RT may have high toxicity (e.g.head and neck
sites)
-- Not for patients with- a)Localised disease with curative intent
b) Disease where durable local contol is
important(e.g.cord compression)

17. Objective of radiotherapy
• To treat involved nodes and regions at high risk for
containing disease to a dose associated with a high
likelihood of tumour irradiation.

18. Indications in Hodgkin’s ymphoma (ILROG
2014)
• As primary treatment
1. Early-stage nodular lymphocyte-predominant Hodgkin’s
lymphoma(nLPHL)
2. Selected cases of early-stage classic HL in patients who
are not primary candidates for chemotherapy.
• RT as part of combined modality approach
1) Early stage classic HL : after adequate systemic CT
2) Advanced stage disease
• Localised RT for residual lymphoma after full CT
• Integral part of some regimens for advanced-stage
disease.

21. Evolution of RT techniques

22. EFRT(Extended field RT)
• SUPRADIAPHRAGMATIC FIELDS
- Mantle field
- Mini Mantle field
- Modified Mantle field
• SUBDIAPHRAGMATIC FIELD
- Inverted-Y field

23. MANTLE FIELD
• Involves all nodes from base
of skull to 10th thoracic level.
• Includes:
• B/L cervical
• B/L supraclavicular
• B/L infraclavicular
• B/L axillary
• B/L hilar
• B/L mediastinal

24. Field Simulation
• Supine
• Neck extended
• Arms above the head, or at 90 degree angle towards
the side, or in ‘akimbo’ position

25. Field Design
• Superior : Bisects the mandible and passes through
the mastoid process
• Lateral : Both the axillae
• Inferior axillary margin : At the level of the inferior
tips of the scapulae
• Inferior mediastinal border: T10-11 interspace

26. • Head of humerus is
shielded both anteriorly
and posteriorly.
• Larynx is shielded
anteriorly.
• Heart is shielded below the
hilar level without including
the mediastinal lymph
nodes both anteriorly and
posteriorly.
• Spinal cord shielding is
done for dosages >40 Gy.
• A small block is put at the
inferior border of spinal
cord posteriorly.
• Oral cavity is shielded if the
superior border includes
the oral cavity.

27. DOSE PRESCRIPTION
• Beams : Parallel opposed
• SSD : at 100-120 cm(Extended SSD)
• Field Size : 40X40 cm2
• Dosage : 36-40 Gy (Standard dose at Stanford was 44
Gy)

28. MINI MANTLE AND MODIFIED
MANTLE
Mini Mantle : Hilar and
Mediastinal lymph nodes
excluded.
Modified Mantle : Axillary
lymph nodes excluded.

29. SUBDIAPHRAGMATIC FIELDS
INVERTED-Y FIELD
• Target volume
 Para-aortic
 Pelvis
 B/L inguinal nodes
 Spleen

30. Treatment fields
For para-aortic
• Superiorly : The T10-11 vertebrae
• Inferiorly the lower limit of L4
• Laterally : width of transverse process
 Pelvis field:
• Laterally : 1.5-2 cm lateral to the widest point in
pelvis.
• Inferiorly :Lesser trochanter.

32. Blocks
• Central midline block for-
 Bladder
 Small bowel
 Ovaries(Oophoropexy)
 Testicular shielding

34. IFRT
• Rationale behind using IFRT :
 Chemotherapy is effective notably for microscopic
disease, therefore large field are no longer necessary.
 Consolidating RT to involved LNs after a limited no.
of Chemotherapy cycles remains a necessity.
 RT-induced complications are dependent on
irradiated volume and the total radiation dose.
 It is therefore of utmost necessity to decrease the
size of radiation fields and to limit radiation doses.

35. IFRT
• Most commonly used technique at present.
• Targets a smaller area rather than a classical extended
field.
• IFRT Definition(ASTRO 2002)
o IFRT encompasses region and not an individual lymph
node.
o Initially involved pre chemo sites and volumes are
treated.
o Exception to above rule is for transverse diameter of
mediastinum and para-aortic lymph nodes for which
reduced post-chemo volume is treated.

36. Rules for IFRT
• All patients must have pre- and post-chemo cervical and
thoracic CT scans(axillary lymph node areas must be
clearly visible on thoracic CT scans).
• The remission status after chemotherapy should be
determined for each initially involved LN exclusively using
CT scans.
• Complete remission(CR) is defined as the complete
disappearance of clinically and/or radiologically
detectable disease.
• CRu is defined as atleast 75% decrease in tumour size.
• A partial response (PR) is atleast a 50% decrease in
tumour size.
• Failure is less than a 50% decrease or any increase in
tumour size.

37. Field for IFRT

38. Cervical chain

39. Axillary Field

40. Mediastinal Field

41. Para-aortics/Groin

42. 3DCRT

43. INRT(Involved Node Radiotherapy)
• Includes the originally involved nodes before
chemotherapy.
• Requires FDF-PET before and after chemotherapy in the
same treatment position for accurate target delineation.
• Concept : Recurrence usually occurred in the initially
involved node.
• INRT should be commenced 3-4 weeks after the
completion of chemotherapy

44. Volume Definition(EORTC)
• The concept of INRT for early stage classic HL was
developed and implemented by the EORTC
• GTV : If CR is not applicable
If PR : post CT volume
• CTV : Initial volume of lymph node with exclusion of
normal displaced structures (e.g.muscles, blood
vessels)
• PTV : If CR, 1 cm isotropic margin of CTV
If PR, PTV1 : CTV+1 cm isotropic margins
PTV2 : GTV+1 cm isotropic margin

45. Techniques needed - EORTC
• Whenever feasible, pre-chemotherapy PET-CT in RT
planning position
• 3D, 4D, IMRT
• If conventional then field size needs to be approx.
5 cm X 5 cm

46. Contouring
• 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.

47. • 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.

48. • The pre-CT PET/CT is fused with the post-CT planning
CT-scan , and the GTV-CT and the GTV-PET are
imported to the planning CT images.

49. • 4. The post-CT 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 tumour
shrinkage and other anatomic changes.

50. • CTV
 Encompasses all the initial lymphoma volume.
 Still respecting normal structures that were never
involved by lymphoma, such as lungs, chest wall,
muscles and mediastinal normal structures.

53. ISRT
• The concept of ISRT was developed on the basis of
the INRT concept.
• ISRT accomodates 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 judgement in conjunction with the
best available imaging is used to contour a larger CTV
that will accommodate the uncertainities in defining
the pre-chemotherapy GTV.

54. • If pre-chemotherapy imaging is available, but image fusion
with the post-CT planning CT scan is not possible
• To contour the pre-CT 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.
• 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 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 these
informations, making generous allowance for many
uncertainities in the process

57. Two additional RT techniques for NHL
• 1) TBI (Total body irradiation)
• 2)WAI (Whole abdomen irradiation)
• 1)TBI
Utility :
• Immunosuppression(lymphocytic cell kill) allow
engraftment of donor marrow
• Eradication of malignant cells (Leukemia, lymphomas and
some solid tumours)
• Eradication of cell population with genetic disorders
(e.g.Fanconi’s anaemia, Thalassemia major)

58. TBI
Treatment program
• Myeloablative treatment program- fractionated or
hyperfractionated regimens over days – decrease
toxicity and treatment time
Dose- 10-13.5 Gy in 1.2-2 Gy/# once or twice a day
Shielding – checked with portal images
• Non-myeloablative treatment program –
Dose – 2 Gy in a single #
Shield – not required

59. Whole Abdomen Irradiation
• Indication – widespread abdominal involvement
stage II
• Technique – parallel opposed anterior and posterior
field
• Border – Diaphragm to superior portion of pelvis or
inferior portion of obturator foramen
• Shielding – iliac bones, femoral head, right lobe of
liver, kidney (>18 Gy)
• 3D planning desirable

61. Short term side effects of RT
• Local skin redness and irritation
• Local temporary hair loss
• Fatigue
• Mouth sores/sore throat/taste changes/dry
mouth(head and neck)
• Esophagitis(chest)
• Nausea/vomiting(stomach)
• Diarrhoea/cramps(pelvis)

62. Late effects of RT
• Eye : cataracts, dry eye
• Salivary glands : dry mouth,dental caries
• Thyroid glands : hypothyroidism
• Lungs : Lung scarring
• Heart : heart disease
• Ovaries or testes : sterility
• Second malignancy

63. Summary
• Multiple recent trials demonstrated important role of
RT as part of lymphoma therapy
• Doses of RT have decreased over time for most
lymphoma cases
• Modern RT technique allows significant sparing of
normal tissue
• Reduced doses and normal tissue exposure will limit
side effects of RT

64. Thank You