Oncology Flashcards
Vemurafenib
MOA
Indication
AE
Protein kinase inhibitor
Unresecatble stage IIIC or IV BRAF V600+ve metastatic melanoma
Arthralgia, rash, photosensitivity, fatigue, GI upset, alopecia, palmar-plantar erythrodysaesthesia
Pembro
MOA
Indication
AE
Anti-PD1 antibody
Advanced melanoma
What is the most common side effect of Erlotinib?
Rash
- resembles acne and primarily involves face and neck
MOA of erlotinib?
inhibits tyrosine kinase associated with epidermal growth factor receptors therefore reducing angiogenesis and tumour progression
Erlotinib
Indications?
NSCLCa.
- 1st line in Stage IIIB or Stage IV (mets) with activating EGFR mutations
- maintenance therapy in pts with locally advanced or metastatic NSCLC who have not progressed on 1st line chemotherapy
- patients with locally advanced or metastatic NSCLC who have previously received chemo
Pancreatic cancer
- used in combination with gemcitabine
indicated in locally advanced, unresectable or metsatic pancreatic ca
what is the most emetogenic chemotherapy agent?
> 90%
- Cisplatin
Cyclophosphamide > 1500 mg/m2
Least emetogenic
List vesicant cytotoxic drugs commonly used
Cisplatin Rubicins Mechlorethamine Mitomycin C Mitoxantrone Oxaliplatin Paclitaxel Vinblastine Vincrisitine Vinorelbine
BRAF mutation MOA?
BRAF mutation consist of a substitution of glutamic acid for valine at amino acid 600 (V600E) which leads to constititive activation of downstream signalling in the MAP kinase pathway
List the BRAF inhibitors
Vemurafenib
Dabrafenib
Staging and Tx of NSC lung cancer?
Staging:
Stage I:
- no nodes
Tx- Sx resection +Adj CTx
Stage II:
Nodes on ipsilateral side
Peribronchial and hilar LN
Tx - Sx resection +Adj CTx
Stage III:
nodal disease to mediastinum/subcarinal LN, supraclavicular.
Tumor with invasion of structures above + N2 nodes.
IIIa: ipisliateral
Tx- neoadjuvant CTx followed by Sx or CTx
IIIb: contralateral
Tx: CTx or palliative RTx
Stage IV
distant mets which include
- contralateral lung nodules
- PLEURAL nodules
- MALIGNANT PLEURAL OR PERICARDIAL EFFUSION
Tx:
Palliative RTx
However systemic Tx should be offered to all pts with ECOG 0-2
- Platinum doublet CTx e.g. cisplatin/gemcit 4-6 cycles. Prolongs OS and improves QOL.
- evidence that addition of bevacizumab to platinum doublet in non-squamous NSCLC results in improved RR, PFR, OS.
What is the recommended duration of therapy for adjuvant hormone therapy in premenopausal breast cancer, ER positive?
10 years (lancet, 2013)
What CTx dugs cause peripheral neuropathy?
Platinum e.g. oxalipaltin
Taxanes
Vincristines
What therapy is recommended for all patients receiving aromatase inh?
Vit D and Ca
When do you commence Denosumbab?
If T score
T/F. Absolute benefits of Aromatise Inh are better than Tamoxifen?
True
What is the Tx for a pt with grade 2 intraductal ca with no associated lymphovascular invasion, sentinel nodes clear, ECOG 0, HER 2 +ve?
AI and Taxane based chemo
Do not use combination of anthracycline and trastuzumab as both are cardiotoxic
Elderly female with bony mets secondary to Stage II breast ca treated with mastectomy, triple -ve. What Tx do you offer?
Palliative RTx and denosumab
Which tumours are chemo resistant?
RCC
GIST
Well diff sarcoma - low chemo responsiveness
What is the medical Tx for RCC?
TKI pazopanib/sunitinib
mTOR-I everloimus, temsirolimus
GIST: What RF Types Mutation Tx
Rare tumour from mesenchymal tissue of GIT
Most common form of sarcoma
Most commonly gastric 50-60% and small intestine 30%
RF: Age Familial Carney's triad (GIST, paragnaglioma, pulmonary chondroma) Type 1 NF
Types:
Spindle cell
Epitheliod
MIxed
Mutation:
Onogene c-kit (CD117) in 75-89% of GIST
PDGFR mutations in 10%
Tx: Localised GIST - Sx Post operative therapy: - Imatinib (c-kit inhibitor). AE: periorbital oedema, fatigue and diarhhoea.
Imatinib delays recurrence but NO overall survival
Advanced disease:
90% response rate to imatinib
Acquired mutations in C-kit or PDGFR are the main cause of imatinib resistance.
Sunitinib 2nd line.
Pt on Imatinib for GIST. Progresses. Next Tx?
Increase dose of Imatinib.
If progresses, sunitinib is 2nd line therapy after high dose imatinib
3rd line therapy: Regorafenib, sorafenib, nilotinib
No indication for Sx
List the tumour that corresponds to the marker:
AFP
Beta-HCG
CA15.3
CA-19.9
CA 125
CEA
AFP - Non seminoma
Beta-HCG
- > 10, 000 mIU/mL = Germ cell tumour (Pure Seminoma)
CA15.3
- metastatic breast cancer
CA-19.9 - pancreatic. Monitor response to Tx, recurrence in resected pancreatic ca.
CA- 125 - ovarian
CEA - Colon cancer
List the common AE for the following biological agents:
Bevacizumab (human monoclonal ab VEGF inh)
Erlotinib (reversibleTKI acting on EGFR)
Temsirolimus (derivative of prodrug sirolimus, mTOR inhibitor)
Sorefenib - TKI (VEGF and PDGRF)
Trastuzumab- (AI- monoclonal ab interferes with HER2 rec)
Bevacizumab - HT, bleeding, proteinuria, impaired wound healing
Erlotinib - Skin rash, diarrhoea
Temsirolimus - stomatitis, rash, hyperglycaemia, hyperlipidaemia, pneumonitis
Sorefenib - fatigue, diarrhoea, hand-foot synd
Trastuzumab - reversible cardiomyopathy
When Tx HCC, what do you consider prior to initiating Sorefnib?
Child Pugh Class
Sorafenib is 1st line Tx in Child Pugh Class A with advanced disease (Stage C, portal invasion)
What is the DNA repair mechanism by which BRCA 1 and 2 proteins act?
Double stranded DNA break repair
Pt is a carrier for BRCA 1 gene mutation with a strong family history of breast ca. What Tx is recommended?
prophylactic bilateral salpingoophrectomy is recommended to reduce the risk of breast and ovarian cancer
Rituximab in addition to standard therapy has been proven to be beneficial over standard therapy alone in the induction phase Tx of Class III -IV lupus Nephritis. T/F
False
In hypercalcaemia, Bisphosphonates increase survival. T/F
False
Zoledronic acid reduces the chance of skeletal related events by 15%. Zoledronic acid has greater reduction than Denosumab. T/F for each.
True
False
Oropharyngeal cancer. Factors associated with improved survival?
HPV associated oropharyngeal cancer have a significantly better prognosis at presentation and after disease recurrence compared with other patients.
Early N stage
Negative surgical margins
p16 positivity (indicates HPV +ve)
Gemcitabine AE?
Dyspnoea, 23% of patients
Small fraction develop severe dyspnoea due to pulmonary toxicities such as interstitial pneumonitis, diffuse alveolar damage, pleural effusions, capillary leak syndrome with noncardiogenic pulmonary odema and others
CT - bilateral ground glass opacities, reticular opacities and thickened septal lines. Centrilobular nodules cans be seen.
What is pulmonary lymphangitis carcinomatosis?
Part of the spectrum of metastatic disease.
Microhaematogenous spread to the periphery of the lung with subsequent lymphatic extension toward the hillier region is responsible for 75% of patients. Usually bilateral.
Remaining cases are due to centrifugal extension from a hillier tumour or from an ipsilateral lung or breast ca. In this case the lymphanggitis spread is unilateral.
Which chemotherapy has the greatest risk for infertility?
Cyclophosphamide - amennorhea and male sterility
Which CTx cases irreversible pulmonary fibrosis?
Bleomycin
Which CTx causes infusion toxicity (hypotension) and delayed neutropenia?
Rituximab
Which CTx causes peripheral neuropathy?
Platinums e.g. oxaliplatin, exacerbated by exposure to cold temperatures
and Taxanes
Vincristine causes dose limiting neuropathy
Bortez and thalidomide also commonly cause peripheral neuropathy
For castrate resistant prostate cancer with bony metastasis, what Tx has been shown to improve overall survival?
Taxanes e.g. docetaxel
Cisplatin is one of the most emetogenic chemotherapy agents. What are its AE?
Neutoxicty
nephrotoxicty
Magnesium wasting
What is the single strongest factor for poor survival in breast ca?
Lymph node involvement
2nd is tumour size of primary
What is crizotinib?
Alk inhibitor
Tx of NSCLCa with alk mutation
What is the Mx for progressive prostate cancer with no mets and life expectancy
Radiation
- less invasive and less likely to cause severe urinary incontinence and errectile dysfunction as with radical prostatectomy
TURP - Hormonal Tx - will not produce relief of LUTs - if pt has CVD, may aggravate
Single agent CTx with docetaxel or cabazitaxel should be reserved for pts with castration recurrent metastatic prostate cancer
What are the poor prognostic factors in breast ca?
65 y - higher co-morbidity
Pathologic factors: Stage IV - 5YS 18% Tumour size, >5 cm 5YS 63% Nodal involvement (axillary nodes) Grade Lymphovascular invasion
Tissue markers:
ER -ve
HER2 over expression - unfavourable prognosis
Aromatase inhibitors e.g. anastrozole, letrozole.
MOA
Most significant AE.
MOA:
Inhibits the enzyme aromatase thereby blocking the conversion of testosterone to oestrodial.
NS inhibitors aromatase and letrazole are reversible.
Steroidal inhibitors e.g. exemestane irreversibly bind the aromatase enzyme
AE:
Osteoporosis and fractures most significant.
Others: Hot flushes mood swings sexual dysfunction CVS Hypercholesterolaemia Arthralgia, joint stiffness, bone pain
SERM e.g. Tamoxifen.
MOA
AE
MOA:
Blocks oestrogen receptor in breast tissue .
However it is a mixed agonist/antagonist and works as an agonist in other tissues such as bone.
AE: Hot flushes Mood swings Sexual dysfunction Thromboembolic disease Uterine cancer
When is Breast MRI indicated?
Asymptomatic women
Mechanism of Hypercalcaemia in malignancy.
Mx of Hypercalcaemia?
Most common in breast, lung and MM.
3 main mechanisms:
- tumour secretion of parathyroid hormone related protein is the most common cause, 80%
- osteolytic metastasis with local release of cytokines, including osteoclast activating factors
- tumour production of calcitriol (most common in HL)
Mx:
1st line IVF
IV bisphosphonates, zoledronic acid is more potent and effective.
Calcitonin - increases renal excretion of calcium and interferes with osteoclast-mediated bone resorption
Glucocorticoids - effective when secondary to calictriol production (lymphoma and sarcoid).
Dialysis - last line
Lung ca. Which mutations more common in never smokers?
EGFR
ALK rearrangement
Which type of lung cancer is more common in nonsmokers?
Adenocarcinomas
Which type of lung cancer is more common in heavy smokers?
SCC
SCLC
What is the rationale for post Tx surveillance for CRC.
Early identification of recurrent disease for potential of cure by further surgical intervention and
Screening for secondary primary cancers and polyps e.g. resectable liver or pulmonary mets.
Colonscopy should be performed 1 year after resection pf a sporadic cancer.
If normal, than 5 yearly.
If poly found, than 3 yearly.
FU every 6 months for 2-3years.
Surveillance program for CRC?
Hx, exam, CEA q 3-6 months for 2 years then q6 months for a total of 5 years
CTCAP q 12 months for 5 years
Colonoscopy at 12 months
- if advanced adenoma repeat in 1 year
- if no advanced adenoma, repeat in 3 years then every 5 years
Significance of MMR gene in CRC?
MMR gene mutations lead to microsatellite instability.
Germline mutations in MMR = Lynch syndrome
Amsterdam criteria for Lynch syndrome?
> =3 family members with confirmed CRC, one is a 1st degree relative of the other 2
2 successive generations affected
1 person
What is the loss of expression of MMR genes in 15% of sporadic tumours due to?
epigenetic changes i.e. acquired hypermethylation of promotors of both alleles of MLH1 that silence gene expression
Activating BRAF mutations are nearly universal in sporadic MSI-H CRC but rare in Lynch cancers.
What are the features of HPV associated oropharyngeal ca: Type of cancer expression of p16 protein p53 RF Age at Dx Anatomical location Prognosis
SCC Over expression of p16 protein p53 wildtype decreased levels of pRB Do not have other RF for head and neck cancers Age 40s Cancer located at base of tongue or tonsillar region Better prognosis
What are the features of HPV negative associated oropharyngeal ca: Type of cancer expression of p16 protein p53 RF Age at Dx Anatomical location Prognosis
SCC low expression of p16 protein p53 mutation Increased levels of pRB Have traditional RF- smoking, EtOH age 50s Any head and neck region worse prognosis
Which cancer Tx are commonly associated with infertility?
Mx?
Alkylating agents e.g. cyclophosphamide
Cisplatin
Radiation to pelvi region or testes
Mx:
Males - sperm banking
Females - embyro cyropreservation if male partner
Cryopreservation of oocytes
Insufficient evidence to support the use of GNRH as ovarian suppression during Tx
Which therapies improve survival in metastatic hormone refractory prostate?
Docetaxel
Carbazitaxel
After Docetaxel, Abiraterone + prednisone improves survival.
Prior to Docetaxel CTx, improvement in radiographic progression free survival but not OS.
Enzalutamide post docetaxel CTx improved OS
Abiraterone. MOA, Indication, AE?
Androgen synthesis inhibitor by blocking
cytochrome P450 17 alpha-hydroxylase (CYP17).
Blocks the synthesis of androgens in the tumor as well as in the testes and adrenal glands.
Indication:
Metastatic prostate cancer
AE:
Abiraterone causes mineralocorticoid excess resulting in fluid retention (eg peripheral oedema), hypokalaemia and hypertension. Although the incidence and severity of these effects are reduced by using abiraterone with a corticosteroid (eg prednisolone), they are still common.
Enzalutamide. MOA, Indication, AE?
MOA:
binds to the androgen binding site in the androgen receptor, thereby leading to inhibition of nuclear translocation of the androgen receptor, and inhibition of the association of the androgen receptor with nuclear DNA
Indication:
metastatic prostate cancer (with GnRH agonist)
AE:
dry skin, hypertension, anxiety, memory impairment; fractures (may be related to increased incidence of falls)
GnRH agonist AE:
impotence, reduced libido (more common with cyproterone); gynaecomastia, breast pain (more common with nonsteroidal anti-androgens), hot flushes, sweating, body hair loss, itch, weight changes, headache, mood changes
Goserelin, Leuprorelin and Triptorelin.
MOA
Indication
AE
MOA:
Continuous administration of GnRH agonists inhibits gonadotrophin production, suppressing ovarian and testicular steroidogenesis and inhibiting the growth of certain hormone-dependent tumours.
Indications:
Prostate ca
Breast ca
AE:
decreased BMD, measure BMD q1-2 years. Give Vit D and Ca supplements.
Prostate cancer: altered glucose tolerance, diabetes, anaemia, increased body fat, weight gain, muscle atrophy, hair changes (eg loss of body hair)
Tumour lysis syndrome. Presentation, Tx?
Presentation: 2 or more abnormalities 3 days before or up to 7 days after Tx: Hyperkalaemia Hyperphos Hyperuricaemia HypoCa
Mx:
IVF
Rasburicase more effective than allopurinol
Cardiac monitoring and tests q 6 hrs
Oxaliplatinum AE?
Periperhal neurpathy and cold dysesthesias of the hands and feet
Vincristine AE?
Peripheral neuropathy
Extravasation reaction
Epirubicin AE?
Cardiac toxicity
Extravasation reaction
Capecitabine and 5FU AE?
Rash - palmar plantar syndrome
Coronary artery spasm
Cyclophosphamide AE?
haemorrhagic cystitis
Infertility
What secondary cancers can Alkylating agents cause? e.g. Chlorambucil,
Cyclophosphamide, Melphalan
MDS and AML
Alkylating agents have the highest risk of all CTx agents
What secondary cancers can cisplatin and carboplatin cause?
AML
Dose related and increased risk with RTx
Risk not as high as with alkylating agents
What are post transplant oncological complications?
Rate of malignancy 3-5 x higher
- post transplant lymphoproliferative disease
- SCC of lips, cervix, vulva, skin
- Kaposi sarcoma
- RCC
- HCC
Which cancers is the CEA used to monitor Tx response?
Metastatic breast, CRC, lung, pancreatic and gastric malignancies
What is CEA used for in early CRC vs. Metastatic CRC?
Early CRC
- to detect recurrence after primary Tx as metastases may be resectable and curable
Mets CRC
- monitor response to Tx
Causes of en elevated CEA?
Benign polyps Colitis Cirrhosis Hepatitis Chronic lung disease and smokers
Very rarely is CEA >10-15 ug/L in benign conditions
What is the Tx for liver mets in colorectal cancer?
If resectable
- resect
- 20% 5 yr survival
- addition of CTx improves PFS
If non resectable
- addition of bevacizumab to FOLFOX in 1st line Tx of met disease improves PFS
Liver directed therapies e.g. TACE, RFA do not have sufficient evidence for 1st line therapy.
Obesity increases the risk of cancer. 3% of cancer deaths are due to obesity. Which cancer has the highest risk?
Endometrial cancer, 3 fold.
Increases risk of: Breast, post menopausal CRC Kidney Oesophageal adenocarcinoma Pancreas
Which cancer is most attributable to smoking?
SCC
Which CTx increases the risk of developing lung cancer?
Bleomycin
MOA of apprepitant?
Neurokinin 1 receptor antagonist
Post CTx, neutrophil count reaches its nadir at?
10-14 d
With liposomal doxorubicin, reaches nadir at 14-18d
What is Lynch syndrome(HNPCC): Inheritance Mutation Presentation Dx criteria Associated malignancies
Most common hereditary colon cancer syndrome
2-5% of all CRC
AD
genetic mutations in MLH1, MSH2 and PMS2, MSH6 (loss of expression of these)
If mismatch repair loss, look at BRAF mutation status. If mutated than unlikely to have MMR gene mutation.
Presentation:
Colorectal adenomas develop at 20-30 y
Lifetime risk of CRC is 80% with mean age of Dx at 44y
Proximal location of colon most common site, 2/3 of cases.
Dx Criteria:
3 relatives with an HNPCC associated cancer (coorectal, endometrial, SB, ureter or renal pelvis) and all the following criteria present:
-One 1st degree relative to the other 2
-At least 2 successive generations affected
-At least one case Dx before the age of 50
Exclusion of FAP
Associated malignancies: Endometrial nest most common cancer Gastric Biliary tract Urnary tract Ovarian Small bowel cancer
Tx for SCLCa?
Limited to one hemithorax
- combined CTxRTx
- followed by prophylactic Whole brain RTx (WBRT) improves survival by 5%
Extensive
- CTx alone
What is the most common and most aggressive primary brain tumour?
Dx?
Tx?
Glioblastoma multiforme.
Dx:
Biopsy, histo important for optimal Tx
Tx:
Surgical ressection PLUS
Concurrent Chemo-RTx (temozolamide) followed by CTx alone (Temozolmide - oral alkylating agent).
AFP vs. BCG found in which cancer?
Testicular cancer.
Seminomas - B-HCG
Non seminomas - AFP and B-HCG
Seminomas with AFP should be considered to have a mixed Germ cell tumour = non seminomatous germ cell tumour
Which anti-depressant interferes with the effects of Tamoxifen?
Paroxetine.
A strong inhibitor of the CYP2D6 enzyme that converts tamoxifen to its active metabolite, reducing the amount of active drug that is released.
Increased mortality.
Use venlafaxine or citalopram instead.
NSCLCa. Adjuvant CTx shows survival benefit in which stages?
Stage II and III
Cisplatin doublet
Carcinoid tumour. Cause, Presentation, Ix, Tx?
Slow growing neuroendocrine .
Most common site is ileum.
Can occur in lungs.
Presentation:
Diarrhoea
Flushes
Abdo pain
Ix:
Elevated 5 HIAA concentration
Tx:
Octreotide
- somatostatin analogue which improves symptoms and prognosis in carcinoid syndrome
FAP: Inheritance Mutation Presentation High risk of which cancers Surveillance
AD
APC gene mutation
Presentation:
100-1000s of polyps throughout colorectum at mean age of 16 y.
High risk of:
Colorectal ca - mean age of Dx 39 y
Duodenal and gastric polyps 4.5% lifetime risk
Papillary thyroid cancer hepatoblastoma and CNS
Surveillance:
Yearly colonoscopy or sigmoidoscopy at 10-15 y.
Preventative protocolectomy around 18.
Screen for duodenal adenomas with gastroduodenoscopy.
Genetic testing should be offered to all at risk relatives where the family specific mutation has been identified.
Otherwise genetic testing should only proceed in teh context of genetic counselling.
Peutz-Jeghers syndrome. Inheritance Mutation Presentation Cancer risk associations
AD
Mutation in STK11/LKB1 gene
Presentation:
mucocutaneous melanocytic macules particulalry in the peri-oral region and over the buccal mucosa
GI hamartomatous polyps which may present in early adolescence with abdo pain, bleeding, obstruction or intussusception.
Hamartomatous polyps are usually located in the SI (60-90%) but can be found in colorectum, biliary tract, respiratory tract or GUT.
Cancer risk: 50-90% will develop one malignancy over their lifetime Gastric 30-60% Breast 54% CRC 40% Pancreas 35% Every site affected!
Juvenile polyposis syndrome.
Mutation
Presentation
Dx
Mutation in BMPR1A, SMAD4 or PTEN genes
Presentation: Multiple polys through the GIT Adbo pain Bleeding Diarrhoea Obstruction Intussusception Mean age Dx at 18.5y
Dx:
Based on any of the following:
1) 3 or more juvenile polys in the colorectum
2) Multiple juvenile polys throughout the GIT
3) Any number of polyps coupled with a family Hx of JPS
Oesophageal cancer: Types RF Presentation Ix for Staging Staging Tx
Types:
Adenocarcinoma - more common in western world, affects distal
Squamous cell - 90% overall, more common in developing world, affects proximal oesophagous.
M>F
RF:
SCC- alcohol, tobacco, corsive injury to oesophagus, HPV not proven, precursor is squmouse dysplasia, no proven role fo
Adeno - Smoking, OBESITY, H. pylori, GORD and BE
Presentation:
Progressive solid food dysphagia most common and reduced oral intake.
Anaemia from GI bleeding.
Ix for Staging: Endoscopy diagnostic Endoscopic US- used for staging and accurate for establishing tumour stage CT for distant mets PET- changes staging in 20%
Staging: O = tumour in mucosa 1 = tumour in submucosa 2a = into muscle 2b = into lymph nodes 3 = beyond muscle 4 = mets
Tx:
Stage 0
-endoscopic mucosal ressection
Stage I
- oesophagectomy + lymph node clearance
Stage II and III
- oesophagectomy alone, 5-34% 5 year survival
Neoadjuvant = pre-op CTx and RTx improves survival compared to Sx alone for both cancers
Role of adjuvant CT and RT unclear
Stage IV:
Symptom control
- stent or RTx
CTx controversial, not sown to be superior to supportive care
- 2 drugs (5-FU and cisplatin) is SD
- 3 drugs (epi, cis + 5FU) is alternative with increased toxicity.
No survival benefit.
Gastric Cancer: Types RF Presentation Ix for Staging Staging Tx
Cause:
Gastric cardia - GORD
Non cardia gastric ca - casual link with H. pylori
RF:
M
Age
Classification: Intestinal - most frequent type More common in older men Strong association with H. pylori
Diffuse
- worse prognosis
-younger people
- associated with E-cadherin (CDHi) loss and link with families with CDH1 germline mutations
Role of H. pylori erradication in preventing gastric cancer unclear
Ix for Staging:
EUS
CT
No role for PET
Tx:
T1 (submucosa)
- Sx alone
All other stages
- Sx alone 5 year survival
HCC. When is Sx indicated?
Single lesion
Sorafenib.
MOA
Multikinase inhibitor.
Inhibitors tumour growth by inhibiting intracellular Raf kinases (CRAF, BRAF and mutant BRAF) and cell surface kinase receptors (VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-beta, cKIT, FLT-3, RET, and RET/PTC).
Indication: Tx of unresecatble HCC Tx of advanced RCC Tx of locally recurrent or metastatic progressive differentiated thyroid cancer. AE: diarrhoea Hand and foot reaction HT Abdo pain
Biliary Ca:
Types
Gallbladder, Intrahepatic, Extrahepatic cholangiocarcinomas.
Presentation:
70% inoperable disease
No proven role for adjuvant therapy
Cisplatin and Gemcitabine improves survival in mets disease
Pancreatic cancer:
RF:
Genetics strong RF
1 family member = 1 x risk
2 family members = 6 x risk
Location:
60% head of pancreas
Mx:
Sx is only chance of cure
Adjuvant CTx improves survival
FOLFIRINOX 11.1 months
Cx:
90% die of disease
Colon Ca:
Which stage benefits from adjuvant CTx
Stage 3 (LN +ve):
FOLFOX4 for a fit and well pt
- AE: neuropathy
Oral capecitabine - IV 5FU
Bevacizumab:
Indication
Metastatic Colon Ca
- only active if given with CTx
Proven survival benefit
Cetuximab:
MOA
AE
Binds to EGFR of both tumour and normal cells, competitively inhibiting ligand binding.
Has activity alone and with CTx
K-ras is a predictive biomarker
Indication:
Metastatic colorectal ca- KRAS wildtype (without mutation)
EGFR expressing mestatic colorectal cancer
In combination with FOLFIRI as 1st line Tx or with Irinotecan or
single agent in pts who have failed irontecan and oxaliplatin based CTx.
Head and neck cancer
AE:
acneform rash
Which GI cancers have adjuvant Tx?
Colon
Gastric
Pancreatic
Screening for CRC:
- Normal population
- FHx (1st degree relative) = slightly above average risk
- Two first degree relatives or relative Dx at age
Normal:
FOBT q 2years from 50y
Flex Sig q5 years from 50y
1st degree relative = 2 x risk:
FOBT annually from 50y
Flex Sigmoid q 5 years from 50y
Two 1st degree relatives or relative
HNPCC:
Screening for at risk
Second yearly Colonoscopy at age 25 y or 10 y younger than the youngest affected.
Annual colonscopy in known mutation carriers.
FOBT in intervening years and to those with poor compliance to colonoscopy.
Options for surveillance at other sites from 25-35 y:
Annual transvaginal US + endometrial sampling
Annual check fro CA125 after menopause
2nd yearly GI endoscopy and
Annual UA and Cytology
Hormone replacement associated with highest risk of which cancer?
Breast
Mantle radiotherapy is associated with the highest risk of which cancer?
Breast
Testicular cancer.
Tx for SGCT
Pure seminomas = excellent prognosis
Radical Inguinal orchiectomy PLUS
- Low stage: surveillance (chemo: may reduce surveillance requirement)
- High stage: chemo (platinum based = BEP (bleomycin + etoposide + cisplatin))
Testicular cancer.
Tx for NSGCT
Radical Inguinal orchiectomy PLUS
- Low stage: +/- 1-2 cycles chemo
- If recur: RPLND + chemo
- BEP: bleomycin + etoposide + cisplatin
- or EP
- If recur: RPLND + chemo
- High stage:
- chemo (platinum based - BEP)
Which anticancer agent is the most likely to cause acute resp distress?
ATRA-all trans-retinoic acid
Indicated in APML (think ATRA, FLT3 most common mutated gene)
Cause of false negative PET?
Uncontrolled DM
Meningioma.
Where do they commonly occur?
Commonly occurs in parasellar regions of the base of skull or cerebral convexities.
Most common SE of erlotinib and gefitanib?
Most toxic SE?
Common = rasj 75% and diarhhoea 55%
Toxic:
ILD
