Cancer Flashcards
Common causes of Cancers in the UK ??
1) Breast
2) Lung
3) Colorectal
4) Prostate
5) Bladder
6) NHL
7) Melanoma
8) Stomach
9) Oesophagus
10) Pancreas
Common causes of death from cancer ??
1) Lung
2) Colorectal
3) Breast
4) Prostate
5) Pancreas
6) Oesophagus
7) Stomach
8) Bladder
9) NHL
10) Ovarian
Examples of Carcinogens ??
Aflatoxins (produced by Aspergillus)
- HCC
Aniline Dyes
- Bladder (Transitional Cell CA)
Asbestos
- Mesothelioma & Bronchial CA
Nitrosamines
- Oesophageal & Gastric Cancer
Vinyl Chloride
- Hepatic Angiosarcoma
Name the malignancies caused by various infections
- Viral ??
- Bacterial ??
- Protozoa ??
VIRUSES
- EBV: Hodgkin’s & Burkitt’s L, Nasopharyngeal CA
- HTLV-1 : Adult T-cell Leukaemia/ Lymphoma
- HIV-1 : High grade B-cell Lymphoma
BACTERIAS
- H pylori : Gastric lymphoma (MALT)
PROTOZOA
- Malaria: Burkitt’s Lymphoma
What are the 3 types of Non-Small Cell lung cancers ??
Squamous C C
- Central in location
- a/w PTHrP secretion => Hyper[Ca2+]
- strongly a/w Finger Clubbing
- Cavitating lesions are MC
- HOPA
ADENOCARCINOMA
- Typical Peripheral
- MC type in Non-Smokers
- But maj. of pts. who develop lung adenoCA are smokers
LARGE CELL LUNG Ca
- Typically Peripheral
- Anaplastic, poorly differentiated
- Poor prognosis
- May secrete Beta-hCG
Bone Metastases in Cancers ??
MC tumour causing B metastases are
- Prostate (MCC)
- Breast (2nd MCC)
- Lung (3rd MCC)
MC site
- Spine (MC site)
- Pelvis (2nd MC site)
- Ribs
- Skull
- Long bones
Other than bone pain, features may include
- Pathological #
- Hypercalcaemia
- Raised ALP
Breast Cancer Risk factors ??
BRCA 1 & 2 : 40% lifetime risk of developing Breast or Ovarian Ca
1st deg. Relative
Pre-M relative with Breast Ca
Nulliparity
- 1st Pregnancy > 30yrs (2x more risk in women having 1st child < 25 yrs)
Combined HRT & COCPs
Past Breast Ca
NOT Breastfeeding
Ionising Radiation
p53 gene mutation
Obesity
Previous Sx. for Benign disease
Cervical Cancer: HPV ??
HPV 16, 18 & 33 are particularly carcinogenic
The MC subtypes (6 & 11) are Non-Carcinogenic & a/w Genital warts
Characteristics of Cervical Ca.
Infected Endocervical cells may undergo changes resulting in the devt. of Koilocytes. These have the following characteristics
- Enlarged nucleus
- Irregular nuclear memb. contour
- Hyperchromasia (Nucleus stains darker than normal)
- Perinuclear Halo may be seen
Hallmarks of Thymoma ??
MC tumour of Anterior Mediastinum & is usually detected b/w the 6th & 7th decades of life
A/W
- MG (30-40% of pts. has thymoma)
- Red cell aplasia
- Dermatomyositis
- Also: SLE, SIADH
Causes of Death in Thymoma ??
Compression of Airway
Cardiac Tamponade
Anti-Oestrogen Drugs ??
SERM
Tamoxifen acts as an
- Oestrogen r antagonist & Partial Agonist
- Used in Rx. of ER(+)ve Breast Ca
S/E
- Vaginal bleed, Amenorrhoea
- Hot flashes
- Leg cramps
- VTE
- Endometrial Ca
What are Aromatase Inhibitors ??
Anastazole & Letrozole
- Reduces Peripheral O synthesis
- This is imp. as aromatisation accounts for the maj. of O synthesis in PM women
- Anastazole is used in ER(+)ve breast Ca
S/E
Osteoporosis
- DEXA Scan when initiating Rx.
Hot flashes
Arthralgia, Myalgia
Insomnia
CT induced N & V ??
RF for devt. of symptoms include
- Anxiety
- < 50 yrs old
- Concurrent use of Opioids
Rx.-
- Pts. who are at low risk of developing N & V, METOCLOPRAMIDE is used
- Pts. at High risk of developing N & V, give 5HT3 r Antagonists eg- Ondansetron are often effective when given with Dexamethasone
Hallmarks of Cyclophosphamide ??
Alkylating agent used in the Rx. of Ca & autoimmune conditions
- Works by causing Cross-linking of DNA
S/E
- Haemorrhagic Cystitis (incidence can be reduced by use of Hydration & Mesna
- Myelosuppression
- Transitional Cell CA
Hallmarks of Mesna ??
2-Mercaptoethane Sulfonate Na
- Metabolite of cyclophosphamide called ACROLEIN is toxic to Urothelium
- Mesna binds to & inactivates Acrolein => prevents H Cystitis
What is ECOG Score ??
It is a ‘Performance Status’ scale or a score that measures- Functional Status of the pt.
- Used to decide if a pt. is a good or poor candidate for further Ca Rx.
Grade 0 : Fully active, can do all pre-disease activities without restriction
G1 : Restricted in strenuous physical activity but Ambulatory & can carry out work of light/ sedentary nature
G2 : Ambulatory + Capable of Self care + Can’t carry out any work activities; up & about > 50% of wake hrs.
G3 : Capable of only Limited self care; confined to bed/ chair for > 50% of waking hrs
G4 : Completely disabled; can’t carry self care; totally confined to bed/chair
G5 : DEAD
Hallmarks of Tranexemic acid ??
Synthetic derivative of LYSINE
- Is an Anti-Fibrinolytic that reversibly binds to Lysine receptor sites on Plasminogen or Plasmin => Prevents Plasmin from binding to & degrading Fibrin
- MC used in Menorrhagia Rx
- In Maj. Bleeding, when given within 3 hrs of start of bleed, it is highly beneficial [given as IV bolus followed by Infusion]
Causes of Drug induced Pancytopaenia ??
Cytotoxics
Antibiotics: Trimethoprim, Chloramphenicol
Anti-Rheumatoid: Gold, Penicillamine
Carbimazole ( also causes Agranulocytosis )
Carbamazepine
SUs: Tolbutamide
BRCA 1 & 2 ??
BRCA1 : Chr. 17 & BRCA 2 : Chr. 13
Linked to develop
- Breast Ca (60%)
- Ovarian Ca (BRCA1- 55%; BRCA2: 25%)
- BRCA2 is a/w Prostate Ca in men
Li-Fraumeni Syndrome ??
A D Condition
- Consists of Germline mutations to p53 tumour suppressor gene
- High incidence of malignancies in particular SARCOMAS & LEUKAEMIAS
Dx. when
- Pt. develops Sarcoma under 45 yrs
- 1st deg. relative dx. with any Ca. in < 45 yrs & another family memb. develops malignancy < 45yrs (OR) Sarcoma at any age
Amsterdam Criteria ??
1) >= 3 family members with a confirmed dx. of Colorectal Ca, one of whom is a 1st degree relative (parent, child, sibling) of the other 2
2) 2 successive generations affected
3) >= 1 Colon Ca dx. in < 50 yrs of age
4) FAP has been EXCLUDED
What are the Extra Colonic diseases of Gardners syndrome ??
Skull Osteoma
Thyroid Ca
Epidermoid Cysts
Desmoid tumours
Lynch Syndrome ??
A D
Develops COLON Ca & ENDOMETRIAL Ca at Young age
80% affected will get 1 of the 2 Ca
High risk pts. may be identified using Amsterdam Criteria
Hallmarks of Gardners Syndrome ??
- A D Familial Colorectal Polyposis
- Multiple colonic polyps
- APC gene mutation on Chr. 5
- Due to colonic polyp, most people undergo Colectomy to reduce risk of colorectal Ca
- Extra-Colonic diseases
- Desmoid tumour in 15%
- Now considered a VARIANT of FAP Coli
Hallmarks of SVC Obstruction ??
Is an Oncological Emergency due to SVC compression
- MC a/w Lung Ca
Causes
- Small Cell Lung Ca, Lymphoma
- Metastatic Seminoma, Kaposi’s Sarcoma, Breast Ca
- Aortic Aneurysm
- Mediastinal Fibrosis
- Goitre
- SVC Thrombosis
Features of SVC Obstruction ??
DYSPNOEA (MC symptom)
Swelling of face, neck & arm
- Conjunctival & Periorbital edema
Headache: Worse in the morning
Visual disturbances
Pulseless JVP distension
Rx. of SVC Obstruction ??
Depends on the pt., malignancy
- Endovascular Stenting is often the ToC to provide symptom relief
- Certain Ca. like Lymphoma , Small Cell Lung Ca may benefit from Radical CT or Chemo-RT rather than Stenting
- Glucocorticoids are often used even though the evidence is weak
Hallmarks of Spinal Metastases ??
Pts. can present with Spinal M before developing SC Compression
C/F & Findings
- Unrelenting Lumbar back pain
- Any Thoracic/ Cervical back pain
- Worse with sneezing, coughing or straining
- Nocturnal pain
- a/w Tenderness
Ix.- If no Neuro. signs, MRI whole spine is done in < 1 wk.
Hallmarks of Neoplastic SC Compression ??
It is an Oncological Emergency; affects upto 5% of Ca. pts.
- EXTRADURAL Compression (maj. cases) due to Vertebral body metastases
- MC in Lung, Breast & Prostate Ca.
Ix.- MRI whole spine in < 24hrs of presentation
Features of Neoplastic SC Compression ??
Back Pain
- Earliest & MC symptom
- Worse on Lying down & Coughing
LL weakness
Sensory loss & Numbness
Neuro. Signs depend on lesion level
- Lesion Above L1: UMN signs in legs & a sensory level; Absent reflexes
- Lesion Below L1: LMN signs in legs; Exaggerated tendon reflexes
Perianal numbness
Rx. of Neoplastic SC Compression ??
High-dose DEXAMETHASONE
Urgent Oncological assessment for consideration of RT or Sx.
Hallmarks of Tumour Lysis Syndrome ??
Occur due to Rx. of High-grade Lymphomas & Leukaemias
- Graded using Cairo-Bishop Scoring System
CAUSES
- Can occur in the absence of CT but is usually triggered by introduction of combination CT
- It can sometimes also occur with Steroid Rx alone
Breakdown of Tumour cells => release of chemicals from cells => High K+ & High PO4- levels & Low Ca2+
Lab. & Clinical definition of TLS ??
LABORATORY TLS
Any abnormality in >= 2 of the follo. occurring within 3 days before or 7 days after CT
- UA > 475 umol/l or 25% increase
- K+ > 6 mmol/l or 25% increase
- PO4- > 1.125 mmol/l or 25% rise
- Ca2+ < 1.75 mmol/l or 25% decrease
CLINICAL TLS (Cairo-Bishop)
Any Laboratory TLS + >= 1 of the follo
- Increase in S.Cr (1.5x upper limit)
- Cardiac Arrhythmias or Sudden Death
- Seizures
Rx. of TLS ??
TLS should be suspected in any pt. presenting with an AKI + High PO4- + High UA levels
HIGH Risk of TLS pts. are given:
- IV Allopurinol or IV Rasburicase immediately prior to & during the 1st day of CT
LOW Risk TLS pts. are given
- Oral Allopurinol during CT cycles
Rasburicase & Allopurinol should NOT be given together as this reduces the effect of Rasburicase
Rasburicase Hallmarks ??
Recombinant version of Urate Oxidase, an enzyme that metabolises UC to Allantoin
- Allantoin is much more H2O soluble than UA & is easily excreted by Kidneys
Rasburicase & Allopurinol should NOT be given together as this REDUCES Rasburicase effect
Tumour Markers ??
They can be divided into
- Monoclonal Antibodies against Carbohydrate or Glycoprotein Tumour antigens
- Tumour Antigen
- Enzymes (ALP, Neurone Specific Enolase)
- Hormones (eg.- Calcitonin, ADH)
T Markers have LOW Specificity
Name a few Tumour Markers of-
- Monoclonal Antibodies ??
- Tumour Antigen ??
Monoclonal Antibodies
- CA 125 (Ovarian Ca)
- CA 19-9 (Pancreatic Ca)
- CA 15-3 (Breast Ca)
Tumour Antigens
- PSA (Prostate CA)
- AFP (HCC, Teratoma)
- CEA (Colorectal Ca)
- S-100 (Melanoma, Schwannomas)
- Bombesin (Small Cell Lung Ca., Gastric Ca., Neuroblastoma)
Hallmarks of Positron Emission Tomography ??
PET is a form of Nuclear imaging
Radiotracer used: Fluorodeoxyglucose (FDG)
- Allows a 3D image of METABOLIC activity to be generated using glucose uptake as a proxy
- Images obtained are combined with conventional imaging like CT to decide if a lesion is metabolically active
Uses
- Evaluating Primary & possible Metastatic disease
- Cardiac PET (Not used in mainstream currentky)
Name the Cell Cycle Independent Drugs ??
Platinum compounds
Alkylating agents
Busulfan
Nitrogen Mustards
Nitrosoureas
Procarbazine
Dactinomycin (DNA Intercalation)
Name the class of drugs that act of different phases of Cell Cycle ??
G1 phase (Duplicate Cell content)
- Rb, p53 modulate G1 (restriction point)
1) S phase (DNA Synthesis)
- Antimetabolites: Cytarabine, 5-FU, Hydroxyurea, MTX, Pentostatin, Thiopurines, Cladribine- is cell cycle nonspecific
2) S phase & G2 phase
- Topoisomerase inhibitors: Etoposide, Teniposide, Irinotecan, Topotecan
3) G2 phase (Double check repair)
- Bleomycin (DNA Scission)
- Anthracyclines (DNA Intercalation)
4) Mitosis : Microtubule inhibitors (Taxanes, Vinca alkaloids)
Cancer Therapy targets ??
(1) Nucleotide Synthesis ==> (2) DNA ==> (3) RNA ==> (4) Protein ==> (5) Cellular division
The drugs which inhibit (1) are
- MTX, 5-FU (decrease Thymidine synthesis)
- Thiopurines (decrease De novo purine synthesis)
- Hydroxyurea (inhibits Ribonucleotide reductase)
The Drugs which inhibit (2) are
- Alkylating agants, Platinum compounds: Cross links DNA
- Bleomycin (Breaks DNA strands)
- Anthracyclines, Dactinomycin (DNA Intercalators)
- Etoposide/ Teniposide (inhibits Topoisomerase II)
- Irinotecan/ Topotecan (Inhibits Topoisomerase I)
What re the drugs that target Cellular Division ??
Vinca Alkaloids
- Inhibits Microtubule Formation
Taxanes
- Inhibits Microtubule Disassembly
MoA of Anti-Tumour Antibiotics ??
BLEOMYCIN
- Induces free radical formation => breaks DNA strand
DACTINOMYCIN (Actinomycin D)
- Intercalates into DNA, preventing RNA synthesis
- Cell cycle Non-specific
ANTHRACYCLINES
- Doxorubicin, Daunorubicin
- Generates free radicals, Intercalate in DNA => Breaks in DNA => Decrease Replication
- Inhibits Topoisomerase II
MoA of Antimetabolites ??
THIOPURINES
- Azathioprine, 6-Mercaptopurine
- Purine (thiol) analogs => decrease De novo purine synthesis
- AZA is converted into 6-MP, which is then activated by HGPRT
CLADRIBINE, PENTOSTATIN
- Purine analogs => can’t be processed by ADA => Interferes with DNA synthesis
- S/E: Myelosuppresion
5-FLUOROURACIL
- Pyrimidine analog, bioactivated to 5-FdUMP => Thymidylate synthesis inhibition => decrease dTMP => decrease DNA synthesis
- CAPECITABINE is a prodrug
S/E of
- Bleomycin ??
- Dactinomycin (Actinomycin D) ??
- Anthracyclines ??
- Pulm. Fibrosis, Skin Hyperpigmentation
- Myelosuppression
- DCM (irreversible; prevent with DEXRAZOXANE), Myelosuppression
MoA of Antimetaboliyes ??
CYTARABINE (Arabinofuranosyl Cytidine)
- Pyrimidine analog => DNA chain termination
- Inhibits DNA Polymerase
- S/E: Myelosuppression
HYDROXYUREA
- Inhibits Ribonucleotide Reductase => Decrease DNA synthesis
- S/E: Severe Myelosuppression, Megaloblastic anaemia
MTX
- Folate analog => Competitively (-) DHF Reductase => decrease dTMP => Decrease DNA synthesis
How can DCM be prevented in Anthracyclines Rx. ??
How can Myelosuppression be reversed in MTX Rx. ??
How to prevent Haemorrhagic Cystitis & Bladder Cancer in Nitrogen Mustards Rx. ??
How to prevent Fanconi Synd. in Platinum compounds Rx. ??
DEXRAZOXANE (prevents DCM)
LEUCOVORIN (‘Rescue’)
Mesna compounds
AMIFOSTINE
MoA of Alkylating agents ??
BUSULFAN (Cross links DNA)
- S/E: Severe Myelosuppression, Pulm. Fibrosis, Hyperpigmentation
NITROGEN MUSTARD
- Cyclophosphamide, Ifosfamide
- Cross links DNA & Requires Bioactivation in Liver
- S/E: Myelosuppression, SIADH, Fanconi synd. (Ifosfamide) Haemorrhagic Cystitis & Bladder Ca
NITROSOUREAS
- Carmustine, Lomustine
- Cross-links DNA; Requires Bioactivation in Liver Crosses BBB
- S/E: CNS Toxicity (Seizures, Ataxia, Dizziness)
PROCARBAZINE (MoA unknown)
- Weak MAO inhibitor
- S/E: Myelosuppression, Pulm. Toxicity, Leukaemia, Disulfuram like reaction
Moa Of Platinum Compounds ??
Cisplatin, Carboplatin, Oxaliplatin
- MoA: Cross links DNA; Cell cycle Non-specific
- S/E: Nephrotoxicity (Fanconi Synd.), Peripheral Neuropathy, Ototoxicity
MoA of Microtubule Inhibitors ??
ALL are M phase specific
TAXANES (Doce- & Pacli- Taxel)
- Hyperstabilise Polymerised microtubules => prevents Mitotic spindle breakdown
- S/E: Myelosuppression, Neuropathy, Hypersensitivity
VINCA ALKALOIDS
- Vincristine & Vinblastine
- Bind Beta-Tubulin & inhibits its Polymerisation into Microtubules => Prevent Mitotic spindle formation
- S/E: Vincristine (Neurotoxicity- Axonal neuropathy, Constipation); Vinblastine : Myelosuppression
Radiotherapy is curative in which cancers ??
Certain types Retinal, CNS, Skin, Oropharyngeal, Larynx, Oesophageal, Cervical, Vaginal, Prostate tumours & also certain types of Lymphoma
Metastatic Prostatic Ca + Resistant to 1st line therapy [Goserelin (LHRH analogue)- Anti-androgen therapy] ToC ??
Enzalutamide
