the christie nhs foundation trust updated june 2010 an introduction to the nature and management of...

The Christie NHS Foundation TrustUpdated June 2010

An Introduction to the nature and management of Lymphoma

Radiotherapy in the management of lymphoma

Richard CowanConsultant in Clinical Oncology

13th October 2010

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Radiotherapy in the management of lymphoma

• Background to radiotherapy

• Place of radiotherapy in lymphoma

• Practical details of radiotherapy

• Future developments

Wilhelm Conrad Röntgen

1845 - 1923

Discovered X rays

1.1865

2.1875

3.1885

4.1895

5.1905

Discovered X rays

1.1865

2.1875

3.1885

4.1895 ✓

5.1905

Marie Curie was born in :Q

1.Russia2.Bulgaria3.Poland4.France5.Bolivia

Marie Curie was born in :Q

1.Russia2.Bulgaria3.Poland ✓4.France5.Bolivia

Energy

wavelength Electromagnetic spectrum

Until 1960s Radiotherapy was the only non surgical treatment for lymphoma

How effective is Radiotherapy ?

• Resistant:

• Resistant:– Malignant melanoma

• Resistant:– Sarcomas / melanoma

• Intermediate:

Which of these tumours is NOT Intermediate in terms of radiosensitivity:

1. Breast, 2. Testicular seminoma3. Non small cell lung cancer4. prostate cancer 5. head and neck cancer

Which of these tumours is NOT Intermediate in terms of radiosensitivity:

1. Breast, 2. Testicular seminoma ✓3. Non small cell lung cancer4. prostate cancer 5. head and neck cancer

• Intermediate:– Breast, lung, prostate, head and neck cancer

• Intermediate:• Breast, lung, prostate, head and neck cancer

Sensitive:• Germ cell tumours• Lymphomas

How does Radiotherapy work?

• Ionising radiation damages cells

• The most sensitive cellular component is DNA

Radiotherapy – Biological Aspects

• DNA damage manifests at cell division

• “Early cell kill” v. “late cell kill”

• Related to proliferative activity

Radiotherapy – Biological Aspects

• Early: - usually the cancer

–Skin, GI tract, Bone marrow

• Late:

–Kidney, CNS

If the Kidneys receive a toxic dose of radiotherapy how long after radiotherapy will the patient show maximum

renal impairment?

1. 10 days

2. 4 weeks

3. 3 months

4. 12 months

5. 24 months

If the Kidneys receive a toxic dose of radiotherapy how long after radiotherapy will the patient show maximum

renal impairment?

1. 10 days

2. 4 weeks

3. 3 months

4. 12 months ✓5. 24 months

How does Radiotherapy work?

• The most sensitive cellular component is DNA

•The malignant cell have impaired DNA repair mechanisms

DNA damage can be repaired

Radiotherapy – Biological Selectivity

Normal tissue

cancer

Place of radiotherapy in lymphoma

• Radiotherapy alone for cure

• Radiotherapy in combination for cure

• Palliation

Radiotherapy alone for cure

• 73 yr old woman who presents with a painless lump in the groin

• Biopsy :

Follicular lymphoma

• Biopsy :

Follicular lymphoma

stage IA

• Biopsy :

Follicular lymphoma

stage IA

• FORT Study : 24Gy in 12 # compared with 4Gy in 2#

• Intermediate:– prostate cancer 70Gy

Sensitive :follicular lymphoma 24Gy (4Gy)

Radiotherapy alone for cure• 73 yr old woman who presents with a painless lump in the groin• Biopsy :

Follicular lymphoma stage IA

24 Gy Radiotherapy

3 months later the chance of complete remissionQ

1. 25% - 35%

2. 40% - 50%

3. 55% - 65%

4. 65% - 75%

5. 85% - 95%

Radiotherapy alone for cure• 73 yr old woman who presents with a painless lump in the groin• Biopsy :

Follicular lymphoma stage IA

24 Gy Radiotherapy

3 months later the chance of complete remissionQ

1. 25% - 35%

2. 40% - 50%

3. 55% - 65%

4. 65% - 75%

5. 85% - 95% ✓

• 33 year old woman

• 33 year old woman• Biopsy : Hodgkins lymphoma Stage I A

(nodular lymphocyte predominant)

• 33 year old woman• Biopsy :

Hodgkins lymphoma Stage I A

(nodular lymphocyte predominant)

30Gy in 15# (3 weeks)

• Intermediate:– prostate cancer 70Gy

Sensitive :– follicular lymphoma 24Gy (4Gy)

– Hodgkins lymphoma 30Gy

Radiotherapy in combination

• 32 year old man

With a cough and weight loss

• Hodgkins stage III B

Radiotherapy in combination

• 32 year old man

With a cough and weight loss

• Hodgkins stage III B

• After 6 cycles of ABVD

Following 6 cycles of ABVD

The practicalities of radiotherapy

Dose and duration of treatment

• “Low Dose “

(30 Gy rather than 70Gy)

• Curative : 15 treatments of 2 Gy = 3 weeks

• Shorter treatments :

Palliative Radiotherapy

Dose and duration of treatment summary

• Curative :– Hodgkins 30Gy in 3 weeks (15#)– DLBC 30 Gy in 3 weeks– Follicular 24Gy in 2 weeks

• Palliative• 1 – 10 #

The practicalities of radiotherapy

Low energy

X-rays

e.g. 100KV

Electrons

High energy x-rays

e.g. 6Mev

PET CT

Side effects of radiotherapy

• Acute : - • Acute inflammation :

– Red skin– Mucositis– Bowel upset– Alopecia

• Tiredness

Acute side effects : - Q

1. Start on the first day of treatment and last for the duration of the treatment

2. Start towards the end of the treatment and last for 3 – 4 weeks3. Start on the first day of treatment and last for 3 – 4 weeks post

treatment4. Start towards the end of treatment and last for 3 – 4 months post

treatment

Acute side effects : - Q

1. Start on the first day of treatment and last for the duration of the treatment

2. Start towards the end of the treatment and last for 3 – 4 weeks ✓3. Start on the first day of treatment and last for 3 – 4 weeks post

treatment4. Start towards the end of treatment and last for 3 – 4 months post

treatment

late : - 6 months and beyond :• chronic inflammation :

– Lung (visible on CXR)– Bowel– Salivary glands– endocrine

• 2nd malignancy• cardiac

• Depend upon :

• Dose

• Depend upon :

• Dose (good for lymphoma)

• Depend upon :

• Volume irradiated

• Depend upon :

• Volume irradiated (small is beautiful)

90Y Zevalin

• Zevalin(Ibritumomab)

– Anti-CD20 murine parent of rituximab

• Tiuxetan

– Chelator, conjugated to antibody forming strong urea-type bond

– Stable retention of 90Y

• Yttrium-90

– t1/2 = 64 hours

– Outpatient administration – Beta emission - 5mm

90Y radionuclide

Tiuxetan

Zevalin

Future developments

• Technical advances :

• Imaging

• Delivery–Intensity Modulated Radiotherapy (IMRT)–Image Guided Radiotherapy (IGRT)

Future developments

• New molecules :

–Increase tumour sensitivity–Protect normal tissues

What is for lunch ?

1. A Big Mac

2. Thai Chicken kebabs

3. Bacon butties

4. Salmon and Champagne

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