The use of radiation therapy in the treatment of Lymphoma

1. Lymphoma and Radiation
Robert Miller MD
www.aboutcancer.com

2. New Cancer Cases Per Year
Lymphoma is # 7 in men and # 6 in women

3. Cancer Deaths Per Year
Lymphoma is # 9 in men and # 7 in women

4. Median Age of People Diagnosed in
2005- 2009
All Sites: 66y
Hodgkins 38y
Non-Hodgkins 66y

5. Lymphomas in 2013
Hodgkin 9,290 (12%)
Non-Hodgkin’s 69,740 (88%)
Thomas Hodgkin 1798-1866

6. What is
Lymphoma?
Lymphoma is a cancer that arises from a mutation by a
cell that is part of the lymphatic system.
The lymphatic system includes the lymphocytes, lymph
nodes and other parts of the lymphatic system include
the spleen, thymus, tonsils and bone marrow

9. What is a
Lymphocyte?
A lymphocyte is a type of white blood cell in the
immune system, can be divided into large lymphocytes
and small lymphocytes. Large granular lymphocytes
include natural killer cells (NK cells). Small lymphocytes
consist of T cells and B cells.

10. Stem cells
differentiate into
several kinds of
blood cell within the
bone marrow
B cells mature into B
lymphocytes in the
bone marrow while T
cells migrate to and
mature in the
thymus.
Then they enter the
circulation and
peripheral lymphoid
organs (e.g. the
spleen and lymph
nodes) where they
survey for invading
pathogens and/or
tumor cells.

11. Cluster of differentiation (cluster of designation) (often
abbreviated as CD) is commonly used as cell markers
in immunophenotyping allowing cells to be defined
based on what molecules are present on their
surface.

12. Circulating Lymphocytes
T lymphocytes 70%
B lymphocytes 23%
NK Cells 7%
B cell make up only 23% of circulating
lymphocytes but account for 90% of lymphoma

13. Prognosis and Treatment for
Lymphoma
 Stage
 Histologic type
◦ Non-Hodgkin’s or Hodgkin
◦ B cell or T cell
◦ Indolent of aggressive
 Other risk factors of advanced disease

14. Specific Prognosis Factors for
Hodgkin
 Wide mediastinal mass ( > .33)
 Bulky mass (10 cm or bigger)
 Multiple site, ESR > 50, B symptoms
 Age over 45, male gender
 Anemia or low albumin

15. Types of Lymphoma
All malignancies are based on the
original cell that ‘goes bad’ or mutates
Since the immune system is so complex
the number of distinct lymphomas is
now immense and growing

16. Classification of NHL (Non-Hodgkin's)

17. Classification of NHL (Non-Hodgkin's)

18. Classification of NHL (Non-Hodgkin's)

19. Classification of Hodgkin's
Lymphocyte Predominant (LPHL) (5%)
Classical Hodgkin’s (CHL) (95%)
- Nodular Sclerosis (NSHL)
- Mixed Cellularity (MCCHL)
- Lymphocyte-depleted (LDCHL)
- Lymphoxcyte-rich (LRCHL)

22. NCCN.org

25. Treatment for NHL Lymphoma
Most patients are treated with drug
therapy (chemotherapy or molecular
targeted therapy).
So many different types of lymphoma
the options range from no initial
therapy for slow growing (low grade or
indolent) lymphomas to very intensive
chemotherapy and bone marrow
transplant for aggressive lymphomas

26. Cluster of differentiation (cluster of designation) (often
abbreviated as CD) is commonly used as cell markers
in immunophenotyping allowing cells to be defined
based on what molecules are present on their
surface.

27. CD 20: Normal B Cells and 90% of B Cell NHL
but not on Stem Cells or Plasma Cells
Pluripotent
Stem Cell
Lymphoid
Stem Cell
Pre-B Cell B Cell Activated
B Cell
Plasma
cell

28. Rituximab Antibody
Antibody binding
Receptor
Antibody
Complex
CD20
B Cell
Lymphocyte

29. After Rituximab binds to the CD20 receptor on the B
Cell it leads to death of the cell by multiple
mechanisms

30. Toposomerase
inhibitor
Alkylation
agents
Antimetabolites
Taxanes
Vinka alkaloids
Dividing Cancer
Cell
Traditional Chemotherapy and Mechanism of Action

31. Rituxan, Zevalin, Bexxar
Mylotarg
Campath
Velcade
Gleevac
Sprycel
Herceptin
Erbitux
Vectibix
Avastin
Nexavar
Sutent
Tykerb
Tarceva
Iressa
Solid Tumors
Hematologic Malignancies
Targeted
Therapies

32. Zevalin, is a monoclonal
antibody radioimmunotherapy uses
antibody to which a radioactive
isotope of yttrium-90
Once the antibody
attached to the CD20
receptor or the B cell the
radioactivity form yttrium
kills the cancer cell

33. Bexxar is anti-CD20 monoclonal antibody bound to the
radionuclide iodine-131 which emits both beta and gamma
radiation

34. Role for Conventional Radiation
in NHL?
 SLL localized
 Follicular Lymphoma early stage
 Gastric MALT (H. pylori negative)
 Nongastirc MALT localized
 Mantle Cell, early stage
 Diffuse Large B Cell (esp bulky)
 Cutaneous B-Cell
 Peripheral T-Cell
 Mycosis Fungoides
 Extranodal NK-T

35. Radiation Technique for NHL
 Volume is IF (involved field) just the
node involved based on original size
 Generally Low Dose

36. Low Dose Radiation for NHL

37. Is there still a role for radiation in the
treatment of Hodgkin Lymphoma?
Henry Kaplan at
Stanford pioneered the
use of the linear
accelerator and
radiation treatment of
Hodgkins in the 1960
and 1970’s

38. Role for Radiation in
Hodgkin’s?
 Lymphocyte-predominant early stage
may need radiation only
 Early stages use involved site (IS)
radiation combined with limited
chemoRx (usually ABVD) or more
intensive chemoRx alone with no
radiation
 High Risk (bulky or unfavorable) add
radiation to chemoRx

39. Radiation Doses for
Hodgkin’s

41. 1370 patients with newly diagnosed early-stage
Hodgkin's lymphoma with a favorable prognosis to
one of four treatment groups (German HD10 Trial)
N Engl J Med 2010; 363:640-652
Chemo IF XRT 8 Year
Survival
ABVD X 4 30Gy 94.4%
ABVD X 4 20Gy 94.7%
ABVD X 2 30Gy 93.6%
ABVD X 2 20Gy 95.1%

42. Long Term Risks of Radiation
Radiation
field
Tissue damage (esp
the lungs, heart or
thyroid or bone
marrow) and causing
new cancers (esp
breast or leukemia)

43. Long Term Health Risk after chemoradiation
for early stage Hodgkin’s

44. ABVD Alone versus Radiation-Based Therapy (SNI)
in Limited-Stage Hodgkin's Lymphoma
HD6 Trial
N Engl J Med 2012; 366:399-408

45. Lymphoma and Radiation
Robert Miller MD
www.aboutcancer.com