Cancer Flashcards
What are the 7 main aetiological factors?
Inherited conditions Chemicals Physical Diet Drugs Infective Immune Deficiency
Examples of inherited conditions that cause cancer?
Neurofibromatosis Adenomatous Polyposis Coli (FAP) Familial breast cancer (BRCA 1/2) Von-Hippel Lindau Syndrome P53 (important in all cancers - discovered via Li-Fraumeni syndrome)
Examples of chemicals that cause cancer?
Cigarette smoke --> p53 mutations Aromatic amines --> bladder cancer Benzene --> leukaemia Wood dust --> nasal adenocarcinoma Vinyl chloride --> angiosarcomas
Examples of physical factors that cause cancer?
Radiation (high energy, level of exposure/dose)
Examples of diet factors that cause cancer?
Low fibre diet –> colorectal
Smoked food –> gastric (Japan)
Examples of drugs that cause cancer?
Cytotoxic drugs –> DNA damage
Topoisomerase inhibitors –> leukaemia
Examples of infective agents that cause cancer?
HPV --> inactivates p53 --> cervical/anal EBV --> NHL Hep B --> hepatocellular Retrovirus --> T-cell lymphomas H.pylori --> MALT tumours
Examples of immune deficiencies that cause cancer?
HIV
4 main groups of presenting symptoms in cancer?
Lumps
Bleeding
Pain
Change in function
What does staging and grading indicate?
Prognosis and treatment
What does X and 0 mean in TNM staging?
X = can't be assessed 0 = no evidence
T in TNM?
Primary tumour
Tis = carcinoma in situ
T1, T2, T3, T4 = increasing size and/or local extent of tumour
N in TNM?
Regional nodes
N1, N2, N3 = increasing involvement of regional lymph nodes
(powerful indicator of probable blood-borne mass)
M in TNM?
Distant metastases
M1 = distant mets
What is grading?
Histological - how much tumour resembles normal tissue or has bizarre appearance
GX = can't be assessed G1 = well differentiated G2 = moderately differentiated G3 = poorly differentiated
Significance of stage and grade on treatment?
Breast and bowel - if lymph node involvement, they get adjuvant chemo
Uses of imaging in cancer?
Diagnosis - need histology as well
Staging - CT, MRI
Response assessment - with clinical status and tumour markers
Follow up - routine FU mostly of no proven benefit
Screening - mammography
What is the RECIST system
Used in clinical trials and clinically to assess response to treatment
Complete response (CR) Partial response (PR) Stable disease (SD) Progressive disease (PD)
CT in cancer?
Contrast can be nephrotoxic
Dose of radiation - 1 extra cancer per 1000-2000 scans
Think of pregnancy
MRI in cancer?
Neurospinal, rectal, prostate, MSK and H+N tumours
No known toxicity
No pacemaker or metal allowed! Prosthetic joints okay
Real time MR can be used
USS in cancer?
No radiation, safe, widely available and cheap
Detect mets in ‘visceral’ abdo organs + assess tumour blood flow (doppler)
Guides biopsy and therapeutic procedures
Operator dependent - less reliable for serial imaging
Nuclear medicine in cancer?
Radiosotope-labelled drugs given - distribution measured by Y-camera detection of emitted photons
Bone scintography (bone scan) - standard for skeletal mets
PET scanning in cancer?
Positron emission tomography - detects high-energy photons emitted by short-lived radioisotopes (minimse radiation) - chemically tethered to glucose/somatostatin to form a tracer –> FDG-18
Functional images –> differentiates malignant from benign (malignant takes up more glucose)
usually combined with CT - functional map with detailed anatomy
used where radical treatment appears possible but has high morbidity/mortality (NSCLC) –> may characterise involvement not picked up by size criteria alone on CT, and save patient from having big but futile surgery.
What is sensitivity and specificity of tumour markers?
Sensitivity = ability to detect only those with disease Specificity = ability to define those who are disease free
What are tumour markers used for?
Screening (only high risk individuals) Diagnosis Prognosis Response Relapse
Classes of tumour markers?
Cell surface glycoproteins Oncofoetal proteins Enzymes Intermediate metabolites Hormones Immunoglobulins Nucleic acids
CEA?
Colorectal cancer
Degree of elevation related to clinical stage.
Also elevated in smokers, hepatitis, pancreatitis or gastritis.
CA125?
Ovarian cancer
Expressed on cell surface. Not perfect sensitivity or specificity.
Also elevated in pancreatic, lung, colorectal, breast cancers (usually when disseminated to abdo cavity)
Monitoring does not increase survival and decreases QoL
Alpha fetoprotein?
Hepatocellular cancer
Usually undetectable after 1st year of life.
Also elevated in hepatitis and teratoma.
Indicates poor prognosis.
HCG?
Beta-subunit = Non-seminomatous/seminomatous testicular cancer
Also raised in gestational trophoblastic disease + pregnancy
PSA?
Prostate cancer.
Not sensitive or specific - asymptomatic screening not recommended.
Measures response and surveillance.
Also raised in BPH, rectal exam, prostatitis and UTI
Immunoglobulins?
Paraproteinaemias (e.g. myeloma and Waldenstrom’s Macroglobulinaemia, NHL)
Measured in blood or excretion in urine as light chains
Bence-Jones protein in 40-50% cases of myeloma.
Types of surgery in diagnosis and staging?
Fine needle aspiration cytology
Tru-cut needle biopsy - tumour sampled under LA
Incisional biopsy - sampled @ surgery
Excisional biopsy - whole of a mass removed
What is surgical resection of primary tumour w/curative intent?
Cancer must be localised with adequate margins of clearance to prevent recurrence
Adjuvant radio/chemo can be used –> less radical surgery
Cure can still be achieved by surgery if in local LNs sometimes
What is surgery to reduce bulk of residual disease?
Cytoreductive surgery
Ovarian cancer - shows long term benefit
What is curative surgery for metastases?
In situations where cure possible i.e. solitary lung met, sarcoma, localised liver met
Systemic therapy almost always required too
Examples of palliative surgery?
Bypass procedure in intenstinal obstruction due to abdominal tumour
Orthopaedic pinning of pathological fractures (can also be prophylactic)
Biliary stent in biiliary obstruction instead of choledocojejunostomy
Drainage/indwelling shunts in pleural effusions/ascites - surgical pleurodesis is definitive
Surgical prevention of cancer?
Colectomy in FAP
Bilateral mastectomy in BRCA1/2
How to cytotoxic agents work?
Erradicate occult systemic cancer cells
Target DNA directly/indirectly. Preferentially toxic to cells with high turnover
Indications for chemotherapy?
Neo-adjuvant Primary Adjuvant Palliative Curative Prophylactic
What is neo adjuvant chemotherapy?
Pre-operative treatment
Makes tumour smaller –> less radical surgery and targets occult mets
Osteosarcoma and breast cancer
What is primary chemotherapy?
Tumour which is inoperableor uncertain operability
Decreased bulk may make surgery feasible
What is adjuvant chemotherapy?
Chemo following complete macroscopic clearance at surgery
Treats occult microscopic mets
What is palliative chemotherapy?
Alleviates symptoms and prolongs life when cannot be cured
Carefully balanced decision so that QoL not affected
What is curative chemotherapy?
In some malignancies where there is chance of cure even if metastatic disease at presentation
Germ cell tumours, hodgkins, NHL, childhood cancers
Justifies use of more intensive treatment with increased toxicity
What is prophylactic chemotherapy?
Before overt malignancy occurs
Tamoxifen for breast ca
What are 5 principles of chemotherapy?
- Administer drugs in combinations
- Treatment in cycles of a few weeks
- Administer optimal dose
- Maintenance treatment where evidence supports
- Most effective route of adminstration
Why is chemo treatment given in cycles?
Allows normal cells to recover (haemopoetic stem cells and GI mucosa)
Repeated cycles required to get tumour clearance as any cycle will only kill a proportion of cells
Difference between conventional and high dose chemo?
Conventional = drugs known to be effective, with tolerable side effects. Given in outpatient setting.
High dose = produce much higher toxicity. Need specialised supportive care or they are lethal.
Only justified when long term survival or cure possible.
Example of cancer with maintenance treatment?
Childhood leukaemia –> 18 months maintenance chemo following induction of complete remission.
Examples of routes of adminstration for chemo?
Oral - frees patient from lengthy visits and invasive procedures. CYCLOPHOSPHAMIDE, ETOPOSIDE, CAPECITABINE, TAMOXIFEN
Systemic - most given as bolus or short infusion, or continuous infusion via central line
Regional
Intravesical - superficial bladder Ca
Intraperitoneal - tumours that have spread trans-coelomically (ovarian)
Intra-arterial - tumours with well defined blood supply - hepatic artery infusion for liver mets
Chemotherapy can cure advanced disease in >50% of cases
Hodgkin's disease Testicular cancer Acute lymphoblastic leukaemia Choriocarcinoma Paeds cancers
Chemotherapy can cure advanced disease in <50% of cases
Non-hodgkins lymphoma
Ovarian cancer
Paediatric neuroblastoma
Adult osteosarcoma (Ewings, rhabdomyosarcoma)
Chemotherapy can increase cure rate in high risk loco regional disease
Breast cancer Colorectal cancer NSCLC Oseophageal and gastric cancers Bladder cancer
Chemotherapy can induce remission in most patients
All of the curable ones
Breast cancer
SCLC
Ovarian cancer
Chemotherapy can prolong survival but few cures in advanced disease
NSCLC Colorectal Gastric Breast Bladder Prostate
Chemotherapy can palliate symptoms but limited responses
Renal Melanoma H+N cancer Pancreatic Biliary tract cancers
Three main categories of chemotherapy adverse effects?
Immediate
Late
Myelosuppression
Immediate chemotherapy adverse effects?
GI, GU, Neuro and Alopecia
GI - oral mucositis, diarrhoea, constipation
GU - bladder toxicity (cyclophosphamide + ifosfamide), nephrotoxicity (platinum agents)
ALOPECIA
Reversible, cold cap can be used, psychological impact
NEUROLOGICAL
autonomic neuropathy, central neuro toxicity (cerebellar, isofamide induced encephalopathy), peripheral neuropathy (platinum drugs)
Immediate chemotherapy adverse effects?
Myelo, Cardiac, Hepatic
MYELOSUPPRESSION
N+V - direct stimulation of vom centre, peripheral stimulation, anticipatory causes
CARDIAC Acute arrhythmias (doxorubicin + piclitaxel), coronary artery spasm (5-FU)
HEPATIC
Transient increase in liver enzymes
Immediate chemotherapy adverse effects?
Skin/Soft Tissue and Others
SKIN/SOFT TISSUE
Extravasation (run through fast running drips under supervision to dilute), Plantar-Palmar Erythema (Hand-foot syndrome - 5-FU, goes away on withdrawal), Photosensitivity (5-FU - sunblock), pigmentation (skin and nails - bleomycin)
OTHERS
Myalgia/arthralgia (piclataxel - control with NSAIDs)
Allergic reactions
Lethargy
Late adverse effects of chemotherapy?
SECOND MALIGNANCIES
High dose chemo –> sub-lethal DNA damange –> 2nd cancer
CARDIAC
Fibrosis in young patients (doxorubicin)
FERTILITY
most associated with reduction
Sperm/ova/ovary storage
PULMONARY
Fibrosis (bleomycin)
PSYCHOLOGICAL/SOCIAL
Aetiology of myelosuppression?
TREATMENT RELATED
Toxic to bone marrow –> transient decrease in leucocytes and platelets –> nadir
BONE MARROW INFILTRATION
Malignant infiltration –> pancytopenia (breast, lung, prostate or haem malignancies)
PARA-NEOPLASTIC SYNDROMES
OTHER
Iron deficiency from blood loss/anaemia from treatment (macrocytic but not megaloblastic)
Treatment of treatment-related anaemia?
Recombinant EPO
Hb <100 impairs QoL and would benefit from transfusion
Treatment of thrombocytopenia?
>20 = don't need transfusion if asymptomatic 10-20 = frequently supported by platelet transfusion, esp if complications >10 = significant risk of bleeding (brain) - urgent transfusion
Problems with platelet transfusion?
Repeated administration of plts is associated with development of antibodies.
Failure to increase counts after transfusion needs SINGLE DONOR (not pooled) or HLA-matched platelets.
Symptoms/signs of thrombocytopenia?
Petechial haemorrhage
Spontaneous nosebleeds
Haematuria
Presentation of neutropenia?
WCC <1 x 10^9/L + fever
Pyrexia post-chemo
Investigation/examination of neutropenia?
Examination to find infeciton site (not PR, not vaginal)
CXR
Cultures (blood, throat, urine, sputum)
Treatment of neutropenia?
Broad spec abx (5 days minimum)
Failure to respond after 2 days –> 2nd line abx or consider antifungals (or atypcials)
Prevention of neutropenia?
PROPHYLACTIC ABX
Not generally used. Used if they have COPD or lymphoma - at risk of PCP (use co-trimoxazole)
DOSE MODIFICATIONS Dose reduction (if palliative, yes) - if curative, need to maintain dose if possible.
COLONY STIMULATING FACTORS
Not of proven benefit. In some patients allows dose intensity to be maintained.
Ways in which radiotherapy can be delivered?
Photons/X-rays
Electrons
Radio-isotopes
Protons
EXTERNAL BEAM = most common - delivered by linear accelerator
How does radiotherapy work?
X-rays penetrate deep into body tissue, spare overlying skin –> free radicals/secondary electrons cause DNA damage.
Normal cells can repair damage, cancer cells can’t.
How is radiotherapy delivered?
In a series of small doses (fractions) over a few weeks
Palliative = smaller no. of fractions + smaller dose
Factors affecting RTx?
- Treatment issues - total dose, volume treated, dose per fraction, treatment time
- Co-morbidities - diabetes, IBD, smoking
- Intrinsic radiosensitivity or cancer cells - seminoma/hodgkin’s = v. radiosensitive
Why give chemo alongside RTx?
Concurrent chemo = radiosensitiser
What is 3D conformational RTx?
Individually planned RTx based on 3D shape of tumour - patient has planning CT.
Patient has to be in consistent position for CT scan and delivery of RTx - may need immobilisation with perspex mask in H+N ca
Areas in 3D conformational RTx?
Gross tumour volume (GTV)
Clinical target volume (margin added for microscopic spread)
Planning target volume (PTV) - extra margin for daily variation in position
Side effects of radiotherapy? (ACUTE)
Related to anatomical area receiving treatment. Due to damage of normal tissue, completely resolve once treatment finished
Increase during treatment, peak = first few weeks following end of Tx.
Localised skin reaction, oral mucositis, diarrhoea
Side effects of radiotherapy? (LATE)
Develop at least 3 months after Tx - may be difficult to treat and may need MDT involvement –> surgery.
Damage to cells can’t be repaired.
Lung fibrosis, skin atrophy, infertility.
SECONDARY MALIGNANCY (2-4/10,000 person years) - risk higher in younger patients treated for good prognosis cancer.
What is brachytherapy?
Radiation placed in (intracavity/interstitial), or close to tumour - pt is radioactive.
Minimises dose to surrounding area.
Prostate, gynae, oesophageal, H+N
What are radioisotopes?
Radioactive iodine (I-131)
Taken up by thyroid cells.
Need to stay in lead-lined room until radiation low enough to not pose risk to others.
What are the three ways in which hormonal therapies can work?
Remove source of growth promoting hormones
Inhibit hormones
Increase hormones
Removing source of hormones?
BILATERAL OOPHRECTOMY/ ORCHIDECTOMY
Not really used now
MEDICAL CASTRATION
Men and women (pre-menopausal) - GnRH analogues.
OVARIAN ABLATION (RTx)
AROMATASE INHIBITORS
Post-menopausal women - blocks conversion of chemical to oestrogen in fat and liver
Hormone inhibitors?
TAMOXIFEN
NON-STEROIDAL
bicalutamide - inhibits testosterone in tumour cells + hypothal –> -ve feedback lost and testosterone levels rise
STEROIDAL
cyproterone acetate - inhibits androgen receptor. Substitute for testosterone in hypothal –> -ve feedback –> less GnRH
What is maximum androgen blockade?
Combine non-steroidal anti-androgen with GnRH analogue to prevent an increase in serum testosterone (prostate cancer)
Increasing hormones?
GLUCOCORTICOIDS
Induce apoptosis in malignant lymphoid cells - lymphoma, myeloma, hodkgin’s disease
INDUCE -VE FEEDBACK LOOPS
Oestrogens downregulate GnRH in prostate cancer
DOWNREGULATION OF RECEPTORS
high dose oestrogens in breast ca
PROGESTOGENS
given orally for cancers in progesterone sensitive tissues (breast, endometrial)
Direct inhibition or tumour growth, -ve feedback on pituitary gonadal axis, stimulates appetite (palliative)
Examples of targeted therapies?
Monoclonal antibodies (-mab)
Tyrosine kinase inhibitors (-ib)
mTOR inhibitors (-us)
Monoclonal antibodies?
Trastuzumab (herceptin) - breast cancer (HER +ve)
Ipilimumab - metastatic melanoma
Rituximab
Tyrosine kinase inhibitors?
ORAL DRUGS - METABOLISED BY CYP
Sunitinib - blocks GFs and angiogenesis. Palliative treatment for bowel, pancreatic, neuroendocrine and GI stromal tumours.
Erlotinib - anti EGFR - NSCLC
Vemurafenib - V600E BRAF mutation malignant melanoma
mTOR inhibitors?
ORAL OR IV
Temsirolimus
Everolimus - palliative renal or ER +ve HER -ve metastatic breast ca
Problems with targeted agents?
Targeted therapies are dosed chronically –> better tolerated, ongoing blockade may be necessary for benefit…
Drug interaction risk Mounting costs Emergent toxicity (thyroid with sunitinib) Chronic toxicity (rash, diarrhoea, taste change)
