Oncology Flashcards
Common sites of metastasis for Melanoma (and prognosis)
Skin, Lungs, Liver, Brain
Skin favourable
Lung moderate
Any other visceral organ poor
What form of sun exposure carrier highest risk for Melanoma?
Intermittent (higher risk than prolonged)
What is Superficial Spreading Melanoma?
- Most common type, 70% of cases
- Lesions spread in radial fashion and can be treated curatively with surgical excision
What are the key features of Acral Melanoma?
Lesions occur on palms, soles, nailbeds and are not linked to UV exposure. Extremely poor prognosis with limited response to treatment. Typically don’t have BRAF mutations
What is the most aggressive form of Melanoma?
Nodular Melanoma. Grows in vertical fashion and thus metastasises early. 10% of cases, 50% of deaths. Lesions elevated, not linked to sun exposure.
Stage I Melanoma features and management
0-1mm with or without ulceration, 1-2mm without ulceration.
Can be managed with complete excision alone.
Key poor prognostic markers for Melanoma
Increasing Breslow Depth
Presence of Ulceration
Stage II Melanoma features and management
Thicker tumours than Stage I, but without lymphatic spread or distant mets.
Complete excision required, plus sentinel lymph node biopsy and screening for distant mets. Screening for BRAF mutations should be completed.
Stage III Melanoma features and management
Sentinel Lymph Node Biopsy positive disease, without more distant metastasis.
lymph node dissection reduces morbidity but not mortality.
No role for chemotherapy
Emerging evidence for targeted therapy and immunotherapy in IIIb-IIIc disease.
When is surgical resection appropriate for metastatic melanoma (other than for primary lesion)?
Evidence for surgical resection if there is a single metastatic deposit and local control of the initial lesion has been achieved
When is Immunotherapy indicated (PBS Subsidised) for Melanoma?
BRAF negative disease, progression on targeted therapy
What is a key side effect of BRAF Inhibitors?
Increased SCC and BCC risk
What are the benefits of using MEK inhibitors with BRAF Inhibitors?
MEK proteins are a key downstream oncogene which increases in activity if BRAF therapy used alone. Increase PFS and OS over BRAF monotherapy.
Also reduce risk of BCC and SCC (but increase frequency of fevers)
Most common malignant skin tumour?
BCC
What form of skin cancer may develop in a chronic wound/ulcer?
Marjolin Ulcer - subtype of SCC
When is Radiotherapy indicated for BCC and SCC?
For unresectable primary lesions
What specific class of systemic therapy may be indicated in locally advanced or metastatic BCC?
Hedgehog Pathway Inhibitors: Vismodegib, Sonidegib
What mutation is common in non smoking Asian women with lung cancer?
EGFR
What is the median survival for metastatic lung cancer without active systemic therapy (i.e. best supportive care)?
4-5 months
Which lung cancer subtype is strongly associated with hypercalcaemia of malignancy?
Squamous
What population factors are markers of poor prognosis in Lung Cancer?
Patients from regional/rural areas, Indigenous patients
Follow up post screening colonoscopy
No adenomas: 10 years
1-2 adenomas and all <10mm, no villous features, no high grade dysplasia: 5 years
3-4 adenomas OR any adenoma >10mm, villous features or high grade dysplasia: 3 years
>/=5 polyps: 5-9 1 year; 10 or more <1 year
Possible incomplete or piecemeal excision of large/sessile adenoma: 3-6 months
Screening for patients with FAP
Annual colonoscopy from age 12 until collectors performed
Endoscopy from age 20 (for duodenal cancer - 100% lifetime risk)
Indications for complete colectomy:
- diffuse polyposis (>100)
- multiple polyps >10mm
- severe dysplasia within polyps
- Malignancy
MUTYH Associated Polyposis
1% of colorectal cancer
15% of patients with multiple adenomas and negative APC gene mutation testing
AR inheritance
Usually repairs oxidative DNA damage
Increased CRC risk
Does not cause desmoid tumour formation
2 yearly scope from age 30
MUTYH Associated Polyposis
1% of colorectal cancer
15% of patients with multiple adenomas and negative APC gene mutation testing
AR inheritance
Usually repairs oxidative DNA damage
Increased CRC risk
Does not cause desmoid tumour formation
2 yearly scope from age 30
When to screen for FAP
10 polyps by age 30
20 polyps by age 60
Abdominal wall desmoid tumour
Hepatoblastoma
Congenital hypertrophy of retinal pigment epithelium
Relative with pathogenic APC variant
Most prevalent MMR Gene mutation
PMS2
Most common MMR Gene mutation in patients with Lynch Syndrome associated colorectal cancer
MLH1
Most common malignancy associated with Lynch Syndrome other than colorectal cancer?
Endometrial
Somatic MMR Deficient Colorectal Cancer
70% of MMRD are somatic
Mostly due to BRAF V600E mutation
Causes hyper methylation of MLH1 or PMS2 promoter region
So loss of MLH1/PMS2 → likely somatic → check for BRAF V600E mutation
Mutations/changes to which MMR Genes is most associated with best associated with germline Lynch syndrome?
MSH2 and MSH6 rarely somatic, mostly germline Lynch syndrome
Risk Management for Lynch Syndrome
Consider subtotal colectomy (not absolute indication unlike FAP)
OGD + Colonscopy every 1-2 years from age 25
Total abdominal hysterectomy +/- BSO from age 40
Aspirin
Phases of Mitosis
Prophase: production of sister chromatids with prominent centromeres, which then move to opposite poles
Metaphase: Karyotyping, chromosomes line up in order at metaphase plate
Anaphase: chromatid pairs are lined up, and one chromatid is tethered to each pole. these separate and are pulled to opposite poles
Telophase: mitotic spindle breaks down, chromosomes decondense
Cervical Cancer Screening
Age 25 to 74
Test every 5 years
Breast Cancer Screening
Age 50-74 invited
Age 40-49 and >75 can access free mammogram but not invited
Mammogram used
2 yearly
Alpha Fetoprotein as a tumour marker
Non seminomatous germ cell tumours
Not produced by seminomas or choriocarcinomas
Also used to for HCC screening/monitoring
Beta hCG as a tumour marker
Produced by seminomas and non seminomas, also choriocarcinomas as well as melaoma.
If >10,000 is a GCT (or pregnancy!)
Prognostic marker for seminomas and non seminomas. Good prognosis if <5000
What tumours is LDH used to prognosticate in?
Melanoma, GCTs, NHL, Prostate Cancer
Causes of false positive CEA
Polyps, colitis, COPD/Smoking
Causes of false positive Ca 19-9
Pancreatitis, cirrhosis, CF, Autoimmune disease
False positive Ca-125
High in any peritoneal inflammation: endometriosis, PCOS, Cirrhosis, Ascites, PID, Pleural Effusion
Use of Ca 15.3 and false positive
Used for Breast cancer
Sarcoid can cause false positive
Most favourable prognostic marker in a young male with widely metastatic disease of unknown origin?
positive B-HcG → implies testicular cancer which is curable in metastatic setting
Most likely chemotherapy class to cause premature ovarian failure?
Alkylating agents (cyclophosphamide, Temozolamide)
Where in the cell cycle do microtubule inhibitors act?
Metaphase of mitosis
Where in the cell cycle do topoisomerase inhibitors work?
G2
Where in the cell cycle do antimetabolites work?
THis is MTX and 5-FU
Work in S
Where in the cell cycle do alkylating agents work?
All phases
Where in the cdell cycle do platinums work?
All phases
Where in the cell cycle do hormonal agents work?
G1 (hormones drive growth)
Where in cell cycle do CDK4/6 Inhibitors work?
G1 (prevent transition to S phase)
