Lymphoma and Radiation

Robert Miller MDwww.aboutcancer.com

New Cancer Cases Per Year

Lymphoma is # 7 in men and # 6 in women

Cancer Deaths Per Year

Lymphoma is # 9 in men and # 7 in women

Median Age of People Diagnosed in 2005- 2009

All Sites: 66yHodgkins 38yNon-Hodgkins 66y

Lymphomas in 2013

Hodgkin 9,290 (12%)Non-Hodgkin’s 69,740 (88%)

Thomas Hodgkin 1798-1866

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

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.

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.

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.

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

Prognosis and Treatment for Lymphoma

StageHistologic type

◦Non-Hodgkin’s or Hodgkin◦B cell or T cell◦Indolent of aggressive

Other risk factors of advanced

disease

Specific Prognosis Factors for Hodgkin

Wide mediastinal mass ( > .33)Bulky mass (10 cm or bigger)Multiple site, ESR > 50, B

symptomsAge over 45, male genderAnemia or low albumin

Types of LymphomaAll 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

Classification of NHL (Non-Hodgkin's)

Classification of NHL (Non-Hodgkin's)

Classification of NHL (Non-Hodgkin's)

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)

NCCN.org

Treatment for NHL LymphomaMost 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

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.

CD 20: Normal B Cells and 90% of B Cell NHL but not on Stem Cells or Plasma Cells

PluripotentStem Cell

LymphoidStem Cell

Pre-B Cell B Cell ActivatedB Cell

Plasmacell

Rituximab Antibody

Antibody binding

ReceptorAntibodyComplex

CD20

B Cell Lymphocyte

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

Toposomeraseinhibitor

Alkylationagents

Antimetabolites

Taxanes

Vinka alkaloids

Dividing Cancer Cell

Traditional Chemotherapy and Mechanism of Action

Rituxan, Zevalin, Bexxar

Mylotarg

Campath

Velcade

GleevacSprycel

Herceptin

ErbituxVectibix

AvastinNexavarSutent

Tykerb

TarcevaIressa

Solid Tumors

Hematologic Malignancies

Targeted Therapies

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

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

Role for Conventional Radiation in NHL?

SLL localizedFollicular Lymphoma early stageGastric MALT (H. pylori negative)Nongastirc MALT localizedMantle Cell, early stageDiffuse Large B Cell (esp bulky)Cutaneous B-CellPeripheral T-CellMycosis FungoidesExtranodal NK-T

Radiation Technique for NHL

Volume is IF (involved field) just the node involved based on original size

Generally Low Dose

Low Dose Radiation for NHL

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

Role for Radiation in Hodgkin’s?Lymphocyte-predominant early

stage may need radiation onlyEarly 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

Radiation Doses for Hodgkin’s

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%

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)

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

ABVD Alone versus Radiation-Based Therapy (SNI) in Limited-Stage Hodgkin's Lymphoma

HD6 Trial

N Engl J Med 2012; 366:399-408

Lymphoma and Radiation

Robert Miller MDwww.aboutcancer.com