Treatment modalities and
principles
Radiotherapy
Chemotherapy
Biological therapy
Julian Singer
Case Example
• 56 year old woman presents to breast
screening unit for her 3 yearly mammogram
• Abnormal lesion seen
• Ultrasound confirmed and lymph nodes look
normal : biopsies taken of primary
• Invasive ductal carcinoma
56 yr old woman
• Booked to undergo Wide local excision and
sentinel node biopsy
• 1.5 cm invasive ductal carcinoma excised. 2
sentinel lymph nodes removed both negative
• ER positive , PgR positive, HER 2 negative
56 yr old woman
• What is the Breast MDT likely to recommend ?
Radiotherapy to breast
Tamoxifen
Radiotherapy
• Principle :
• Radiotherapy necessary for local control in
breast conserving surgery
• Evidence : Without external beam
radiotherapy 20 – 40 % local relapse,
depending on studies and risk factors for
primary
• 3% relapse with Radiotherapy
Delivery of external beam
radiotherapy
Radiation mechanism of action
Summary : Mechanism of action
Radiotherapy
• Damages DNA of cancer cells (and normal
cells)
• Faster proliferating cells more sensitive
(cancer)
• Cell death at next mitosis (not immediate)
Radiotherapy side effects : principles
• Early
Fast reacting tissues : skin erythema , mucositis
• Intermediate : Fibrosis and contraction
• Late : Capillaries : telangectasia, lymphoedema
Breast Radiotherapy
Early reaction 6 weeks
Breast Radiotherapy Intermediate
reaction 6 months
Breast Radiotherapy Late reaction
Telangectasia 2-5 years
Future trends : radiotherapy principles
• More targeted and accurate
• Fewer radiotherapy fractions
Future: Cyberknife
Cyberknife for lung cancers
Follows respiratory movement of ribs and lung cancer
Cyberknife for lung cancers
less than 3 cm
Cyberknife
• Expensive
• Each treatment takes an hour +
• But fewer treatments : 1 – 3
• Only available in a few centres
Stereotactic body radiotherapy
Linear accelerator with CT
Lung cancers 3- 5 cm
Stereotactic body radiotherapy
Conclusions
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New
Fewer treatments
Only for small isolated cancers
Long term side effects uncertain
NICE already approves some treatments
Expensive
• Lack of phase III randomised trials
Coming soon Intra-operative breast
radiotherapy
• Faster
• Fewer side effects
• Equivalent results in smaller cancers
• Less travel
The Source of Innovation:
The INTRABEAM® X-Ray Source
• A Miniature
• Linear Accelerator
• that weighs only 1.6 kg
• Emits low energy
X-Rays of max 50 kV
• Only minimum shielding required
• Spherical radiation field
Internal Cathode
Radiation
Gun
Monitor
Accelerator
Section
Beam
Deflector
Electron
Beam
Gold
Target
• Probe length 10 cm
• Probe diameter 3.2 mm
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INTRABEAM® in Operation for treating
Breast Cancer
X-Ray Source
May 2011
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The TARGIT Procedure for
Breast Cancer
with INTRABEAM
Tumor Resection and
Preparation of the Tumor Bed
Placement of
INTRABEAM
and Irradiation
May 2011
Average additional time (preparation + IORT) is 35 minutes
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Conclusion
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Intra operative breast radiotherapy : new
Research trials underway
Good 5 year data for one trial
Not yet NICE approved ? 2015
Less expensive than normal external beam
radiotherapy
• Much more convenient for patients
Chemotherapy
Principles and mechanisms
Example :
• 35 year old woman presents with 3 cm lump
in right breast, nodes in axilla
• Triple assessment : biopsy : IDC grade III
• ER & PgR negative
• HER2 positive
• Surgery : Wide Local Excision and axillary
clearance
35 woman : MDT
• What is the breast MDT likely to recommend?
35 year old woman :
• 6 cycles adjuvant chemotherapy
• Radiotherapy to breast and axilla
• Herceptin
Chemotherapy principles
• Cytotoxic : damages DNA of cycling cells
• Cancer cells
• Normal tissues that divide quickly
Chemotherapy mechanisms
Chemotherapy general principles
• Given in cycles to allow normal tissue recovery
• Bone marrow is key organ
• GITract / mucosa
• Hair , Skin, nails
• Peripheral nerves
Chemotherapy general principles
• Adjuvant or neo-adjuvant setting : curative
• Dose and intensity important
• Palliative setting
• Dose and intensity less important
Biological therapies
More specific target to cancer cells
Human Epidermal Receptors
Herceptin
Herceptin
• Intravenous
• Given in 3 week cycles
• 12 months
• Few side effects
• Cross reaction with cardiac muscle in 3 %
Case No. 3
• 65 year old woman
• Presents with cough, chest pain , breathless
• Non smoker
Investigations
• Chest X ray
• CT scan
• Bronchoscopy and biopsy
Imaging
Diagnosis
• Stage III B
• Adenocarcinoma of lung
• Biopsy sent for Epidermal Growth Factor
Receptor I testing :EGFR
• Found to be EGFR mutation positive
What does the lung MDT
recommend?
Tarceva
Oral inhibitor of EGFR
NICE approved
Expensive
Induces tumour reduction
Extends survival 12 months
Not a cure
Tarceva : side effects : acne and
diarrhoea
Summary of principles of biological
agents
• Curative : Adjuvant setting : Herceptin : (NICE
approved)
• Palliative : Tarceva (NICE approved)
Summary of mechanisms of biological
agents
• Target cancer molecular pathway
• Target cancer cell surface
Thank you
Questions ?