Therapeutic Options: Cancer

Learning Outcomes:

• Illustrate the importance of cell turnover and kinetics on actions of anti-cancer therapies.

• Describe modalities of therapy currently available.

Therapeutic Options: • what are they

- prevention: environment / behaviour change

diet

screening

genetics

medication / vaccination

- treatment: surgery

radiotherapy

systemic therapy

immunotherapy

Therapeutic options: diet

• evidence from cohort studies

inconsistent & lots of confounding factors

CRC : probably a link with red meat consumption

breast cancer : probably a link with saturated fat intake

physical activity decreases risk

• current advice- eat 5 or more portions of fruits and vegetables / day

- avoid obesity

- take regular exercise (30 minutes / day)

• also of benefit for reducing cardiovascular risk

Therapeutic options: diet & environment

• public policy:

smoking in public places

minimal alcohol pricing

water & air quality : electric cars / renewable energy

vaccination : HPV / Hep B

opportunities via schools : physical activity / school meals etc

income & housing policies

• for medical profession: importance of public health specialists & GPs

Therapeutic options: screening

• high quality research evidence available

Cervical cancer: regular smear tests

CRC : faecal occult blood the most commonly used test

16% reduction in CRC mortality

breast cancer : mammography

• more controversial prostate cancer : PSA blood test

lung cancer : MR / CT scanning

breath test

Therapeutic options: genetics

• high quality research evidence available

CRC & familial adenomatous polyposis coli (FAP)

- autosomal dominant

- screen families for APC mutations

- regular colonoscopy

- offer panprotocolectomy when adenomas found

breast cancer & BRCA1 & BRCA2- also important in therapeutic area

Therapeutic options: chemo-prevention

• more controversial

primary: oesophageal cancer

- high rates in parts of China

- supplement diet with anti-oxidants

primary: breast cancer

- known at risk women

- prophylactic tamoxifen

secondary: previous H&N or lung cancers

- give anti-oxidant supplements

- no benefit

Therapeutic Options: ‘treatment’

• what are they

- local or regional treatment

- surgery- radiotherapy

- ablation (freezing, radio-frequency, etc)

- isolated limb perfusion

- systemic treatment

- hormonal therapy

- chemotherapy

- biological therapy

- immunotherapy

- CAR T-cell therapy

- whole body irradiation (for BMT)

Therapeutic Options: staging

• where is cancer

- examination

- use of radiology / imaging

- CT , MRI, USS, PET etc

• what kind of cancer

- pathology / cytology

- classification, risk factors etc

- genomics now plays a role & will increase

- immune / stromal environment will also have a role

Therapeutic Options: Surgery & radiotherapy

• both are ‘local’ therapies

• surgery needs anatomical clearance- of cancers cured about 50% by surgery

• radiotherapy

- needs anatomical coverage

- can treat inoperable lesions

- can make surgery become possible

Therapeutic options: Radiotherapy

5 R’s of radiobiology

• radiosensitivity

• repair

• re-population

• re- oxygenation

• re-assortment

radiotherapy

- of cancers cured ~40% by radiotherapy

- eg head & neck, cervix / uterus, skin, lymphoma

- can be combined with chemotherapy

- eg anal cancer, rectal cancer, oesophageal cancer

- important role in palliation- eg: pain, bleeding, swollen limbs

Therapeutic options: medical treatment

• systemic treatment- beneficial for widespread disease

- can result in widespread toxicity

- now mixture of ‘chemotherapy’ & now targeted agents

• ~ 5% of cancers cured by chemotherapy

• ~50% of cancers have palliative chemotherapy

• targeted agents: potential to be very specific!

- hormone therapy : tamoxifen & ER+ve breast cancer

- targeted a tumour mutation : EGFR mutations & TKI agents

Immune therapies

non specific

‘innate’- macrophages / NK cells

programmed cell death pathway (PD-1)- uses immune system to attack ‘foreign’ cancer cells

• specific monoclonal antibodies

- rituximab & B cell NHL: +/- radioactivity

- trastuzumab & response in HER2 +ve breast & gastric cancer

chimeric antigen receptor (CAR) T-cells

- artificial T-cell receptors, using retroviral vectors to give an specific cell killing function directed against cancer cells

Therapeutic options: summary
• variety of options

• staging of vital importance

• increasing use of genomics

• improvements will come by:

- surgical techniques: reduce morbidity

- radiotherapy: technical (eg through IMRT) combination with systemic treatment

- systemic treatment: more targeted therapies

- immunotherapies: monoclonal antibodies ‘innate’ immune system programmed cell death pathway CAR T-cell therapy

• clinical research very important