Cancer Treatment

Cancer Treatment

·        Treatment objectives:

o  Cure

o  Prolong life expectancy

o  Relieve symptoms

·        Treatment modalities:

o  Chemotherapy

o  Radiotherapy

o  Symptomatic/Supportive

Treatment of Colorectal Cancer

·        No role for radiotherapy in colon

·        Adjuvant chemotherapy: 

o   Improves 5 year survival over surgery alone from 50 to 60/65% (but can‟t predict who will benefit) 

o  ­Quality of life (side effects of cancer are pretty severe, chemo reduces these)

o  Given after surgery

o  Six months of 5FU

o   Currently given to:

§  Dukes C: All patients (C1 = Muscularis propria + lymph node, C2 = serosa + lymph node) 

§  Dukes B2 (serosa): High risk groups, perforation, invasion of adjacent organs, diploid tumours

·        Rectal cancer:

o   No serosa around rectum – cancer infiltrates straight into fat – harder to get clear resection margins 

o   Radiation in rectal cancer good: but ® impaired function and may irradiate small bowel ® fibrosis. Try and predict who needs irradiation and do it pre-operatively 

·        Palliation: hospice + chemotherapy better quality of life than hospice alone

Treatment of Breast Cancer

·        Can‟t cure metastases ® aim of treatment is local control

·        Options:

o  Two options (similar long-term survival):

§  Removal of the lump + radiation therapy (significant ¯ in local recurrence)

§  Mastectomy (or radical mastectomy) + reconstruction

o  +/- Radiotherapy (planned to limit dose to the heart, lung or opposite breast

o  +/- Tamoxifen (anti-oestrogen)

·        Surgery:

·        Mastectomy      Breast Conservative

·        Patient preference       Patient preference

·        Large tumour or Large tumour/breast ratio        Small tumour or small tumour/breast ratio

·        Multiple tumours         Single tumour

·        +ive margins      Focal microcalcification

·        Previous breast RT       -ive margins

·        Pregnancy, etc, etc     

·        Most common metastasis is in the bone.  Bisphosphonates ® slow osteolysis

·        Risk factors for recurrence in breast cancer (Þ consider adjuvant chemo):

o  Axillary node status (strongest predictor)

o  Tumour size (> 1 cm)

o  Histological tumour type and grade

·        Adjuvant Chemotherapy:

o   Approx 25 – 30% ¯ risk of recurrence, 15 – 20% ¯ risk of death. Improves long term survival in node positive and node negative disease 

o   4 to 6 courses over 3 – 6 months optimal

o   2 agents better than one: eg 

§  AC: Adriamycin (an anthracycline) and Cyclophosphamide. „Gold standard‟. Adriamycin causes vomiting and wasn‟t used so much until 5HT3 antagonists were available

§  CMF: Cyclophosphamide, Methotrexate and Fluorouracil (another „Gold Standard‟)

·        Hormone Therapy:

o   Aim: prevent breast cancer cells from receiving stimulation from oestrogen

o   Only is oestrogen receptor sensitive

o   Oestrogen deprivation:

§  Block oestrogen receptor: eg Tamoxifen – antagonist.  Taken for 5 years.  Side-effects:

·        Largely well tolerated

·        1 in 3 have post menopausal flushes, vaginal dryness/discharge

·        Initial nausea, weight gain

·        Rare retinopathy 

·        Agonist in the uterus ® ­endometrium ® ­risk of endometrial carcinoma (1 in 1000, usually curable) 

·        PE/DVT (1 – 2 %) 

§  Suppress synthesis: aromatase inhibitors (work in adipose tissue, eg in post menopausal women), LHRH agonist (pre-menopausal, switches off the ovary)

§  Destroy ovaries (surgery or RT) 

o   Leads to ¯recurrent, ¯ 40% incidence of contralateral breast cancer (although absolute risk low)

Radiotherapy

·        Superficial X-ray: for skin cancers

·        Cobalt: no longer used in the west.  Max 1.2 MV

·        Linear accelerators:

o  6 MV to 18 MV

o  Skin sparring

o  Produces electrons and photons.  Biological effect of photons is to create free radicals 

o  Does lots of damage to the cell – but only damage which affects reproductive integrity is DNA damage

o  Most DNA damage is repaired within 6 – 8 hours, but if lots of damage then non-repair

o  More damage is done to cells in G2 (ie in mitosis) as DNA is super coiled

·        Effective use requires:

o  Good planning: how to maximise dose to the lesion while minimising dose to unaffected tissue

o  Immobilising the patient

·        Use of multiple fractions (ie lots of small doses) spares normal tissue as this has time to repair, but tumour tissue doesn‟t repair so well

·        Uses:

o  Aim is curative in head and neck, skin, cervix

o  Anal (with chemo), rectal (with surgery)

o  Adjunct in lung, stomach cancer

·        Toxicity:

o  Acute: builds up during treatment and settles within ~ 6 weeks

§  Affects rapidly dividing cells and secretory function

§  Skin: erythema, desquamation

§  Mouth: mucositis and dryness

§  Gut: diarrhoea, colic, ileus

§  Bladder: cystitis

§  Marrow (only if widespread dosing): leukopaenia, thrombocytopenia

o  Late:  Months to years 

§  Due to healing with fibrosis or ­aging of tissues

§  Affects slowly or non-dividing cells and causes permanent damage

§  Skin: Telangiectasis, fibrosis 

§  Mouth: Dryness (¯parotid function), caries, osteoradionecrosis

§  Gut: stricture, fistula

§  Bladder: contracture, haematuria

§  Nerves: myelitis, necrosis, neuropathy

Chemotherapy

·        Systemic treatment with single or multiple agents

·        Damages DNA/RNA protein synthesis ® cell death/apoptosis.  Not tumour specific

·        Predictable side effect depending on the schedule.  Side effect management has improved greatly

·        Can be oral, sc, im, iv, continuous iv

·        Adjuvant Treatment = after local therapy has removed cancer but where there is a statistical chance of relapse (eg due to micro metastases)

·        Uses:

o   Can be curative in: lymphoma (esp Hodgkin‟s), leukaemia (including ALL), sarcomas of childhood, Germ cell tumours (Testicular teratoma, Seminoma), etc

o   Adjuvant in breast, large bowel and ovarian cancer 

o   Prolongation of life: Ovarian, lung (small cell lung cancer is sensitive to chemotherapy), bowel, breast

o   Relief of symptoms: shortness of breath, pain/discomfort, local disease

o   Not in melanoma, renal cell carcinoma

·        Side effects:

o   General:

§  Feeling terrible till 2 – 3 days later

§  Nausea: 5HT3 antagonists to help

§  Lethargy, anorexia

o   Affect on fast growing tissues:

§  Mucous membranes: mouth ulcers, diarrhoea

§  Hair loss: not inevitable (depends on regime) but always temporary

§  Bone marrow: myelosuppression, anaemia, neutropenia, thrombocytopenia

o   Irritant effects: haematuria, sore eyes

o   Neutropenia: typically 1 –3 weeks following.

o   ¯Fertility (especially in men) but no risk of future fetal abnormality (unless pregnant at the time). NOT a reliable contraceptive

Other treatment options

·        Hormones

·        Immunotherapy