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 • • • • • • 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 Radiation Monitor Cathode Gun Accelerator Section • Probe length 10 cm • Probe diameter 3.2 mm Beam Deflector Electron Beam Gold Target 23

INTRABEAM® in Operation for treating Breast Cancer

X-Ray Source

May 2011 24

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 (prep aration + IORT) is 35 minutes 25

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

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 ?