Treatment modalities and principles

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Treatment modalities and principles

• Radiotherapy
• Chemotherapy
• Biological therapy
• Julian Singer

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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

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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

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56 yr old woman

• What is the Breast MDT likely to recommend ?

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Radiotherapy to breast

• Tamoxifen

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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

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Delivery of external beam radiotherapy
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Radiation mechanism of action
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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)

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Radiotherapy side effects principles

• Early Fast reacting tissues skin erythema ,
  mucositis
• Intermediate Fibrosis and contraction
• Late Capillaries telangectasia, lymphoedema

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Breast RadiotherapyEarly reaction 6 weeks
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Breast Radiotherapy Intermediate reaction 6 months
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Breast Radiotherapy Late reactionTelangectasia
2-5 years
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Future trends radiotherapy principles

• More targeted and accurate
• Fewer radiotherapy fractions

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Future Cyberknife
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Cyberknife for lung cancersFollows respiratory
movement of ribs and lung cancer
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Cyberknife for lung cancers less than 3 cm
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Cyberknife

• Expensive
• Each treatment takes an hour
• But fewer treatments 1 3
• Only available in a few centres

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Stereotactic body radiotherapy

• Linear accelerator with CT

• Lung cancers 3- 5 cm

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Stereotactic body radiotherapy
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Conclusions

• 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

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Coming soon Intra-operative breast radiotherapy

• Faster
• Fewer side effects
• Equivalent results in smaller cancers
• Less travel

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The Source of InnovationThe INTRABEAM X-Ray
Source

• A Miniature
• Linear Accelerator
• that weighs only 1.6 kg
• Emits low energyX-Rays of max 50 kV
• Only minimum shielding required
• Spherical radiation field
• Probe length 10 cm
• Probe diameter 3.2 mm

Internal Radiation Monitor
CathodeGun
Accelerator Section
GoldTarget
ElectronBeam
BeamDeflector
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INTRABEAM in Operation for treatingBreast Cancer
X-Ray Source
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The TARGIT Procedure for Breast Cancerwith
INTRABEAM
Tumor Resection and Preparation of the Tumor Bed
Placement ofINTRABEAMand Irradiation
Average additional time (prep-aration IORT) is
35 minutes
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Conclusion

• 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

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Chemotherapy

• Principles and mechanisms

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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

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35 woman MDT

• What is the breast MDT likely to recommend?

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35 year old woman

• 6 cycles adjuvant chemotherapy
• Radiotherapy to breast and axilla
• Herceptin

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Chemotherapy principles

• Cytotoxic damages DNA of cycling cells
• Cancer cells
• Normal tissues that divide quickly

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Chemotherapy mechanisms
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Chemotherapy general principles

• Given in cycles to allow normal tissue recovery
• Bone marrow is key organ
• GITract / mucosa
• Hair , Skin, nails
• Peripheral nerves

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Chemotherapy general principles

• Adjuvant or neo-adjuvant setting curative
• Dose and intensity important
• Palliative setting
• Dose and intensity less important

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Biological therapies

• More specific target to cancer cells

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Human Epidermal Receptors
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Herceptin
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Herceptin

• Intravenous
• Given in 3 week cycles
• 12 months
• Few side effects
• Cross reaction with cardiac muscle in 3

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Case No. 3

• 65 year old woman
• Presents with cough, chest pain , breathless
• Non smoker

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Investigations

• Chest X ray
• CT scan
• Bronchoscopy and biopsy

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Imaging
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Diagnosis

• Stage III B
• Adenocarcinoma of lung
• Biopsy sent for Epidermal Growth Factor Receptor
  I testing EGFR
• Found to be EGFR mutation positive

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What does the lung MDT recommend?
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Tarceva

• Oral inhibitor of EGFR
• NICE approved
• Expensive
• Induces tumour reduction
• Extends survival 12 months
• Not a cure

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Tarceva side effects acne and diarrhoea
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Summary of principles of biological agents

• Curative Adjuvant setting Herceptin (NICE
  approved)
• Palliative Tarceva (NICE approved)

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Summary of mechanisms of biological agents

• Target cancer molecular pathway
• Target cancer cell surface

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Thank you

• Questions ?