the christie nhs foundation trust updated june 2010 an introduction to the nature and management of...
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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
The Christie NHS Foundation TrustUpdated June 2010
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The Christie NHS Foundation TrustUpdated June 2010
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The Christie NHS Foundation TrustUpdated June 2010
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The Christie NHS Foundation TrustUpdated June 2010
Radiotherapy in the management of lymphoma
• Background to radiotherapy
• Place of radiotherapy in lymphoma
• Practical details of radiotherapy
• Future developments
The Christie NHS Foundation TrustUpdated June 2010
Wilhelm Conrad Röntgen
1845 - 1923
The Christie NHS Foundation TrustUpdated June 2010
Discovered X rays
1.1865
2.1875
3.1885
4.1895
5.1905
Q
The Christie NHS Foundation TrustUpdated June 2010
Discovered X rays
1.1865
2.1875
3.1885
4.1895 ✓
5.1905
Q
The Christie NHS Foundation TrustUpdated June 2010
1898
The Christie NHS Foundation TrustUpdated June 2010
Marie Curie was born in :Q
1.Russia2.Bulgaria3.Poland4.France5.Bolivia
The Christie NHS Foundation TrustUpdated June 2010
Marie Curie was born in :Q
1.Russia2.Bulgaria3.Poland ✓4.France5.Bolivia
The Christie NHS Foundation TrustUpdated June 2010
Energy
wavelength Electromagnetic spectrum
The Christie NHS Foundation TrustUpdated June 2010
The Christie NHS Foundation TrustUpdated June 2010
The Christie NHS Foundation TrustUpdated June 2010
Until 1960s Radiotherapy was the only non surgical treatment for lymphoma
The Christie NHS Foundation TrustUpdated June 2010
How effective is Radiotherapy ?
• Resistant:
The Christie NHS Foundation TrustUpdated June 2010
How effective is Radiotherapy ?
• Resistant:– Malignant melanoma
The Christie NHS Foundation TrustUpdated June 2010
How effective is Radiotherapy ?
• Resistant:– Sarcomas / melanoma
• Intermediate:
The Christie NHS Foundation TrustUpdated June 2010
How effective is Radiotherapy ?
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
Q
The Christie NHS Foundation TrustUpdated June 2010
How effective is Radiotherapy ?
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
Q
The Christie NHS Foundation TrustUpdated June 2010
How effective is Radiotherapy ?
• Resistant:– Sarcomas / melanoma
• Intermediate:– Breast, lung, prostate, head and neck cancer
The Christie NHS Foundation TrustUpdated June 2010
How effective is Radiotherapy ?
• Resistant:– Sarcomas / melanoma
• Intermediate:• Breast, lung, prostate, head and neck cancer
Sensitive:• Germ cell tumours• Lymphomas
The Christie NHS Foundation TrustUpdated June 2010
How does Radiotherapy work?
• Ionising radiation damages cells
• The most sensitive cellular component is DNA
DNA
The Christie NHS Foundation TrustUpdated June 2010
Radiotherapy – Biological Aspects
• DNA damage manifests at cell division
• “Early cell kill” v. “late cell kill”
• Related to proliferative activity
The Christie NHS Foundation TrustUpdated June 2010
Radiotherapy – Biological Aspects
• Early: - usually the cancer
–Skin, GI tract, Bone marrow
• Late:
–Kidney, CNS
The Christie NHS Foundation TrustUpdated June 2010
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
Q
The Christie NHS Foundation TrustUpdated June 2010
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
Q
The Christie NHS Foundation TrustUpdated June 2010
How does Radiotherapy work?
• The most sensitive cellular component is DNA
•The malignant cell have impaired DNA repair mechanisms
DNA
DNA damage can be repaired
The Christie NHS Foundation TrustUpdated June 2010
Radiotherapy – Biological Selectivity
Normal tissue
cancer
Cell
No.
The Christie NHS Foundation TrustUpdated June 2010
Place of radiotherapy in lymphoma
• Radiotherapy alone for cure
• Radiotherapy in combination for cure
• Palliation
The Christie NHS Foundation TrustUpdated June 2010
Radiotherapy alone for cure
• 73 yr old woman who presents with a painless lump in the groin
The Christie NHS Foundation TrustUpdated June 2010
Radiotherapy alone for cure
• 73 yr old woman who presents with a painless lump in the groin
• Biopsy :
Follicular lymphoma
The Christie NHS Foundation TrustUpdated June 2010
Radiotherapy alone for cure
• 73 yr old woman who presents with a painless lump in the groin
• Biopsy :
Follicular lymphoma
stage IA
The Christie NHS Foundation TrustUpdated June 2010
Radiotherapy alone for cure
• 73 yr old woman who presents with a painless lump in the groin
• Biopsy :
Follicular lymphoma
stage IA
• FORT Study : 24Gy in 12 # compared with 4Gy in 2#
The Christie NHS Foundation TrustUpdated June 2010
How effective is Radiotherapy ?
• Intermediate:– prostate cancer 70Gy
Sensitive :follicular lymphoma 24Gy (4Gy)
The Christie NHS Foundation TrustUpdated June 2010
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%
The Christie NHS Foundation TrustUpdated June 2010
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% ✓
The Christie NHS Foundation TrustUpdated June 2010
Radiotherapy alone for cure
• 33 year old woman
The Christie NHS Foundation TrustUpdated June 2010
Radiotherapy alone for cure
• 33 year old woman• Biopsy : Hodgkins lymphoma Stage I A
(nodular lymphocyte predominant)
The Christie NHS Foundation TrustUpdated June 2010
Radiotherapy alone for cure
• 33 year old woman• Biopsy :
Hodgkins lymphoma Stage I A
(nodular lymphocyte predominant)
30Gy in 15# (3 weeks)
The Christie NHS Foundation TrustUpdated June 2010
How effective is Radiotherapy ?
• Intermediate:– prostate cancer 70Gy
Sensitive :– follicular lymphoma 24Gy (4Gy)
– Hodgkins lymphoma 30Gy
The Christie NHS Foundation TrustUpdated June 2010
Radiotherapy in combination
• 32 year old man
With a cough and weight loss
• Hodgkins stage III B
The Christie NHS Foundation TrustUpdated June 2010
Radiotherapy in combination
• 32 year old man
With a cough and weight loss
• Hodgkins stage III B
• After 6 cycles of ABVD
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Following 6 cycles of ABVD
The Christie NHS Foundation TrustUpdated June 2010
Following 6 cycles of ABVD
The Christie NHS Foundation TrustUpdated June 2010
The practicalities of radiotherapy
The Christie NHS Foundation TrustUpdated June 2010
Dose and duration of treatment
• “Low Dose “
(30 Gy rather than 70Gy)
• Curative : 15 treatments of 2 Gy = 3 weeks
• Shorter treatments :
Palliative Radiotherapy
The Christie NHS Foundation TrustUpdated June 2010
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 Christie NHS Foundation TrustUpdated June 2010
The practicalities of radiotherapy
The Christie NHS Foundation TrustUpdated June 2010
The Christie NHS Foundation TrustUpdated June 2010
Low energy
X-rays
e.g. 100KV
Electrons
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High energy x-rays
e.g. 6Mev
The Christie NHS Foundation TrustUpdated June 2010
The Christie NHS Foundation TrustUpdated June 2010
PET CT
The Christie NHS Foundation TrustUpdated June 2010
The Christie NHS Foundation TrustUpdated June 2010
Side effects of radiotherapy
• Acute : - • Acute inflammation :
– Red skin– Mucositis– Bowel upset– Alopecia
• Tiredness
The Christie NHS Foundation TrustUpdated June 2010
Side effects of radiotherapy
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
The Christie NHS Foundation TrustUpdated June 2010
Side effects of radiotherapy
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
The Christie NHS Foundation TrustUpdated June 2010
Side effects of radiotherapy
late : - 6 months and beyond :• chronic inflammation :
– Lung (visible on CXR)– Bowel– Salivary glands– endocrine
• 2nd malignancy• cardiac
The Christie NHS Foundation TrustUpdated June 2010
Side effects of radiotherapy
• Depend upon :
• Dose
The Christie NHS Foundation TrustUpdated June 2010
Side effects of radiotherapy
• Depend upon :
• Dose (good for lymphoma)
The Christie NHS Foundation TrustUpdated June 2010
Side effects of radiotherapy
• Depend upon :
• Dose (good for lymphoma)
• Volume irradiated
The Christie NHS Foundation TrustUpdated June 2010
Side effects of radiotherapy
• Depend upon :
• Dose (good for lymphoma)
• Volume irradiated (small is beautiful)
The Christie NHS Foundation TrustUpdated June 2010
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
The Christie NHS Foundation TrustUpdated June 2010
Future developments
• Technical advances :
• Imaging
• Delivery–Intensity Modulated Radiotherapy (IMRT)–Image Guided Radiotherapy (IGRT)
The Christie NHS Foundation TrustUpdated June 2010
Future developments
• New molecules :
–Increase tumour sensitivity–Protect normal tissues
The Christie NHS Foundation TrustUpdated June 2010
What is for lunch ?
1. A Big Mac
2. Thai Chicken kebabs
3. Bacon butties
4. Salmon and Champagne
Q