HODGKIN’S LYMPHOMA

Dr Sandip BarikDepartment of

Radiotherapy,KGMU,Lucknow

INTRODUCTION

• Are group of cancers which originates from Reticuloendothelial systems

• It was named after Thomas Hodgkin who first described it in 1832.

• Dorothy Reed and Carl Stenberg first described the malignant cells of Hodgkin’s lymphoma called Reed Stenberg cells.

• Hodgkins lymphoma was the first cancer which could be successfully treated by radiation therapy and also by combination chemotherapy.

Epidemiology

• Accounts for 0.58% of all cancers diagnosed and 0.23% of all cancer deaths in U.S each year.

• Incidence is less than 3 per 100,000

• In 2010 in U.S 8490 cases were registered (4670 males, 3820 females) and accounted for 1320 deaths.

• It has a slightly male predominance (1.1:1)

• It is rare in children younger than 10 years

• It has Bimodal peak of distribution (25-30 yrs and >55 yrs)

Risk Factors

• First degree relatives have five fold increase in risk for Hodgkins Disease.

• Associated with EBV infection mainly with mixed cellularity type.

• Associated with Infectious Mononucleosis. Incidence is about 2.55 times higher

• High socio economic status.

• Prolonged uses of human growth hormone

Natural History

• Hodgkins lymphoma arises in a single node or a chain of nodes and spreads first to anatomically contiguous lymphoid tissue.

• Visceral involvement by Hodgkins lymphoma may be secondary to extension from adjacent lymph nodes.

• Haematogenous spread occurs to liver or multiple bony sites

• It rarely involves the gut associated lymphoid tissue such as Waldeyer ring and Peyers patches.

• Mechanism of spleen involvement is unclear but all pts with hepatic and bone involvement are associated with splenic involvement.

Clinical features

• Most common presentation is asymptomatic lymphnode enlargement typically in the neck.

• Cervical lympnodes are involved in 80% cases .

• Mediastinal involvement is seen in about 50% cases .they produce symps likeChest painCoughDyspnoea

• Infradiaphragmatic involvement is seen in 5% cases and usually seen with older patients.

Clinical features cont…

• B symptoms About 33% presents with B symptoms overall. Only 15-20% of stage I-II have B symptoms like

o Fever(>38oC) May first present as fever of unknown origin

Fever persists for days to weeks followed by afebrile intervals and then recurrence

Such type of pattern is called Pel Ebstein Fever

o Drenching night sweats

o Weight loss(> 10% in 6 mths)

Clinical features cont…

• Other less frequently symptoms are

Pruritus

Alcohol induced pain over involved lymph nodes

Nephrotic syndrome

Erythema nodosum

Cerebellar degeneration

Immune hemolytic anaemia, Thrombocytopenia

Hypercalcaemia

Diagnostic Workup

• History • Complete physical examination• Confirmatory workup

Excisional biopsy of the lymph node

Staging workup

Chest x ray(pa,lat) Usg neck,whole abdomen CT scan thorax,abdomen and pelvis FDG PET scan

• Routine blood investigations

Complete blood count Liver function Renal function Serum albumin ESR Lactate Dehydrogenase

OTHERS Bone marrow biopsy

PET SCAN

• PET Scan has become an integral component of initial staging.

• Information provided by PET has been recently incorporated in the lymphoma guidelines for response evaluation after completion of treatment.

• Useful for follow up study to evaluate residual masses , dx of early recurrence and predicting outcome.

• It has a specificity of 90-95%

Revised International Workshop Criteria With PET Scan

Bone Marrow Biopsy

• Less commonly put into practice

• Overall involvement of bone marrow in Hodgkins lymphoma is 5%.

• Indicated in pts with B symptoms Clinical evidence of sub diaphragmatic disease Stage iii-iv Recurrent disease

Pathological Classification

Histologic Subtypes

Nodular lymphocyte predominant Hodgkins lymphoma(NLPHL)

Classical Hodgkins lymphoma(CHL)

1 Nodular sclerosis Hodgkins lymphoma

2 Lymphocyte rich classical Hodgkins lymphoma

3 Mixed cellularity Hodgkins lymphoma

4 Lymphocyte depletion Hodgkin lymphoma

Lymphocyte predominant Hodgkins lymphoma

• <5% of Hodgkins lymphoma

• Mainly involves cervical,axillary or mediastinal

• “L&H” cells or Popcorn cells are seen

• Positive for CD20,45

• Negative for CD15,30.EBV

Nodular Sclerosis

• Most common type diagnosed. About 70%

• Lacunar ceells are seen

• CD 15 and 30 positive

• EBV negative

• Only subtype without a male predominance

• Seen in younger pts with stage I –II disease

Mixed Cellularity

• Constitutes about 20%

• More common in young children

• CD 15,30 EBV positive

• Presents in advanced stages

• Tendency to involve spleen,bone marrow

Lymphocyte Depleted

• Constitutes <5%

• Worst prognosis of all subtypes

• Older males

• Advanced stage

• HIV infection

Staging

I Involvement of a single lymph nodeOr,lymphoid structureOr single extralymphatic site

II Involvement of two or more lymphnode region on same side of diaphragmLocalized contiguous involvement of only one extranodal organ or site and lymphnode regions on same side of diaphragm

III Involvement of lymphnode regions on both side of diaphragm

III1 With or without involvement of splenic,hilar.celiac or portal nodes

III2 With involvement of paraaortic ,iliac,and mesenteric nodes

IV Diffuse or disseminated involvement of one or more extranodal organs or tissues,with or without involvement of associated lymphnodes.

Lymphnodes group

Prognostic Factors

Prognostic factor for Early stage Hodgkins disease

Prognostic factors cont…

Advanced stage hodgkins lymphoma International prognostic score

Management

RADIATION CHEMOTHERAPY

Chemotherapy

25mg/m2106375

Radiotherapy

• Radiation therapy is the most effective single therapeutic agent for treating Hodgkins lymphoma.

• The main objective of radiation in Hodgkins lymphoma is to treat involved and contiguous field.

• Radiotherapy can be given by

• 2D Planning• 3D Planning• IMRT

• Pre RT Evaluation: Oro dental prophylaxis Pulmonary function test Pre chemotherapy and post chemotherapy information from CT or PET scan

Position Usually supine. Arms up position pulled up the axillary node further from the chest

wall ,thereby permitting more generous lung shielding. Arms down or akimbo position permitted shielding of the humeral head

and minimize the effect of tissue folds in supraclavicular If neck is to be treated head in hyperextension Frog leg for inguinal nodes

• Immobilization

Mask for head and neck Body cast for pelvis

OTHERS Oophoropexy in young females Fields are shaped using multileaf collimators Respiatory gating has to be taken care of

Mantle technique

• Target volume definition.

The target volume for mantle field includes the Occipital Submental Submandibular Ant and Post cervical Infraclavicular Axillary Medial pectoral Paratracheal Mediastinal and hilar nodes

• Treatment Field:

Superiorly: Inferior portion of mandible bisecting the mastoid process

Laterally: Both the axillae

Inferiorly: T10-11 interspace

• BLOCKS : Larynx anteriorly

Humeral heads

Spinal cord if >40 Gy

Heart after 30 Gy

Lung blocks: The upper border of lung block curves centrally to include infraclavicular nodes The medial borders are shaped so as to treat the hilar nodes. A gap of 8-10 cm is left in midline between blocks to treat mediastinal nodes.

Subdiaphragmatic Fields

• The classical subdiaphragmatic field is the Inverted-Y.

• Target Volume:

Para aortic

Pelvis

Inguinal nodes(b/l)

Spleen

• Treatment Fields: For Paraaortic

Superiorly:The T10-11 vertebrae Inferiorly:The lower limit of L4 Laterally:width of transverse process.

Pelvis F ield:

Laterally:1.5-2 cm lat to the widest point in pelvis Inferiorly:Lesser trochanter.

Inverted “Y” Field

Para aortic fields pelvic field

• BLOCKS:

Central midline block for

Bladder Small bowel Oophoropexy if performed

Testicular shielding

IFRT

• Involved field radiotherapy.• IFRT is the most commonly used technique at present• Targets a smaller area rather than a classical extended field.• IFRT(ASTRO 2002)DEFINITION

IFRT encompasses region and not an individual lymph node.

Initially involved Pre chemo sites and volume are treated

Exception to above rule is for transverse diameter of mediastinum and paraaortic lymphnodes for which reduced post chemo volume is treated.

Major fields of IFRT

IFRT

3DCRT

• GTV:Original prechemo volume of involved lymphnodes clinically and radiologically

• CTV:GTV with whole nodal regions that contains the involved lymphnodes.

• PTV:Depends on immobilization,reproducibility,organ motion.usually 10 mm margin is added to CTV

• INRT• Newer concept evolved with advent and more usage of ct and PET scan• Target volume is based on initial macroscopic prechemo disease rather

than based on lymphnode region.

• Treatment Portals: Beam arrangement is often // & opposite pair fields(ap-pa)

DOSE Early stage :after complete response to chemotherapy 20 Gy in 10# Advanced stage with residual disease after chemotherapy 30 Gy in 15# with additional 6 Gy in 3# depending on bulk of disease

Sequelae of Treatment• ACUTE REACTIONS: Fatigue ,nausea,vomiting,dry cough

Occipital hair loss

Sore throat

Skin reactions

Alteration of taste

Dysphagia

Reflux symptoms

Myelosupression

• LATE REACTIONS Radiation Pneumonitis(6-12 wks)

Radiation Pericarditis

Subclinical Hypothyroidism:most common delayed symotoms

Herpes Zoster infections:

Lhermittes sign(1-2 mths)

• Late Reactions(cont…)

Streptococcus pneumoniae and H influenzae infection following splenic radiation.

Azoospermia in males

Premature menopause in females

Secondary malignancy:• Leukaemia• Lymphoma(diffuse large cell type most common after 5 years)• Solid Tumors:In males Lung (>30 Gy),colorectal

In females Breast,lung,colorectal

Conclusion

• Radiation therapy is the most effective single therapeutic agent for treating Hodgkins lymphoma

• The management of Hodgkins lymphoma has evolved from extended field radiation to a combined modality of chemo radiation or chemo alone.

• Interest is in achieving the best therapeutic ratio by minimizing late toxicity while maintaining effectiveness.

• With improvement in diagnostic modality and PET scanning and improved treatment policy the results in future will be encouraging.

THANK YOU