Oncology Flashcards
Management of CUP presenting as axillary lymphadedopathy in women:
MRI may find identify primary when mammography normal –> breast conservation.
Treat as Stage II breast cancer
- 50-60% have occult primary tumour at mastectomy even if exam / mammography normal
- same survival rates as stage II BrCa
Definition of CUPS:
Cancer of Unknown Primary Site
Tumour detected at ≥1 metastatic sites but routine evaluation fails to define a primary site.
Workup for CUPS:
Hx & Exam Pelvic exam in women Prostate exam in men Basic bloods - FBC, eLFTs Urinalysis CXR CT C/A/P Mammography (if appropriate clinical presentation) PSA in men
+/- PET
+/- extra tests in specific settings (eg. breast MRI in woman with axillary LNs).
- Immunohistochemistry (specific staining patterns) - Eg. PSA in PrCa; Eg. HER2, ER, PR in BrCa; Eg. CK20+/CK7 in liver mets from CRC.
- Molecular tumour profiling
Tumour markers (CEA, CA19.9, CA15.3, CA125) - not useful diagnostically or prognostically and should be interpreted with caution, but may be used to monitor response to Tx.
Management of CUP presenting with inguinal lymphadenopathy:
- TRY TO IDENTIFY PERINEAL / PELVIC PRIMARY AS CURATIVE Tx MAY BE AVAILABLE.
Unilateral lymphadenopathy of the groin -primary sites usually: skin, anus, rectum, pelvis, lower urinary tract. - No primary found –> superficial groin lymph node dissection –> half will live for >2 years.
- significant proportion may have unclassifiable carcinomas that are likely amelanotic melanomas.
Management of CUP presenting with cervical lymphadenopathy:
SCC:
AdenoCa:
Management of CUP presenting as peritoneal carcinomatosis in women:
Often + malignant ascites
Look for ovarian source.
If none found, may arise from peritoneal surface which has a similar histogenesis.
CA125 often raised in both.
Treat as stage III ovarian cancer: cytoreductive surgery, then chemotherapy
Management of poorly differentiated carcinoma (CUP):
Mediastinal or retroperitoneal in young men:
Management of CUP presenting as skeletal metastases in a man:
Most common primaries with bone mets: lung, prostate
Less often: liver, kidney, thyroid, and colon.
If sclerotic (osteoblastic) highly suspicious for PrCa. Test serum PSA and do PSA staining on IHC.
If strong suspicion then treat as for advanced PrCa (offers additional therapies).
Primary tumour sites associated with sclerotic (osteoblastic) bone mets:
Prostate Ca
Carcinoid
SCLC
HL
Medulloblastoma
POEMS syndrome
Mixed (OB/OC): Breast Ca, GI tumours, SCC (most sites)
Primary tumour sites associated with lytic (osteoclastic) bone mets:
RCC Melanoma MM NSCLC NHL Thyroid cancer Langerhan's histiocytosis
Mixed (OB/OC): Breast Ca, GI tumours, SCC (most sites)
Management of CUP at single site:
PET to rule out other sites
Often other secondaries will become evident in short space of time
Consider unusual tumour (could be mistaken for met), eg: apocrine, eccrine, sebaceous carcinoma.
Excision and/or XRT if no other sites identified.
If poorly differentiated adenoCa / carcinoma –> consider platinum-based chemo.
Define Chemotherapy Terms: Adjuvant -
Adjuvant chemotherapy - post-resection to treat residual disease and prevent recurrence.
Define Chemotherapy Terms: Neoadjuvant -
Neoadjuvant chemotherapy - prior to the surgical resection (de-bulk).
Define Chemotherapy Terms:
- Induction
- Consolidation
- Maintenance
Induction chemotherapy - given to induce a remission.
Consolidation chemotherapy - given once a remission is achieved, aim to sustain a remission.
Maintenance chemotherapy - given in lower doses to assist in prolonging a remission (ALL, APML).
Define Chemotherapy Terms: First line -
First line chemotherapy / Standard therapy - best probability of treating a given cancer based on research.
Define Chemotherapy Terms: Second line -
Second line chemotherapy / Salvage therapy -
given when inadequate response or progression with first-line therapy.
Define Chemotherapy Terms: Palliative -
Palliative chemotherapy - given specifically to address symptom management without expecting to significantly reduce the cancer or prolong survival
Management of ACUP presenting with a colon cancer profile:
Colon cancer profile defines patients with ACUP who are likely to respond to treatments for metastatic CRC.
Profile is defined as:
- Predominant metastatic sites in the liver and/or peritoneum
- Adenocarcinoma with histology typical of gastrointestinal origin
- Typical IHC staining: eg. CK20+/CK7- or CDX-2 positive
Treatment for metastatic CRC - eg. FOLFOX / Bevacizumab
Breast resection acceptable strategy at or below which stages?
T<3
M=0
Note: supraclavicular node positive = M1
Age <35 in breast cancer. Good or poor prognosis?
Poor (independent of grade)
Breast conserving therapy for early stage breast cancer - contraindicated in:
- Multicentric disease
- Large tumor size in relation to breast
- Presence of diffuse malignant-appearing calcifications on imaging (ie, mammogram or MRI)
- Prior history of chest wall RT
- Pregnancy
- Persistently positive margins despite attempts at re-excision
Can have neoadjuant chemotherapy (+/- trastuzumab) to increase chance of BCT. No survival benefit (outcome similar to surgery + adjuvant therapy), but may be able to have BCT.
Breast conserving therapy for early stage breast cancer - components:
- breast conserving surgery
- radiotherapy to eliminate residual local disease
- hormonal therapy if ER and / or PR positive
- +/- adjuvant chemotherapy - consideration of risks and benefits in particular case
eg. high tumour grade, tumour size (large ≥2cm), lymph node involvement, etc.
Define stages of breast cancer: Early stage, Locally advanced, Advanced
Early: stages I - IIb(T2N1)
Locally Advanced: stages IIb(T3N0) - IIIc
Advanced: metastatic, ie. stage IV
Adjuvant systemic therapy in early breast cancer - choice of agent:
REVIEW
- Triple negative >0.5cm: chemotherapy
(1cm: trastuzumab
(<1cm controversial) - ER/PR positive: chemotherapy followed by hormonal therapy
Non-seminomatous testicular GCT, early stage (low risk) treatment:
- tumour resection
- clinical surveillance
- previously used retroperitonreal lymph node dissection if unlikely to follow up well
- not radiotherapy
- if stage II-III: multiagent chemo (BEP)
Principles of optimising treatment outcome from combination chemotherapy:
- Use drugs effective as single agents
2. Minimise interaction between drugs
Mantle radiotherapy for HL - risk of further cancers (order)?
- BrCa
- Thyroid
- Lung Ca
Treatment of SBO with ovarian cancer:
octreotide
GIST associated with mutant of which gene?
CKIT mutation
GIST usually responsive to which agents?
Biologic agents: Imatinib
Cell marker CD117 on IHC - association?
GIST
Spindle shaped cells - suggestive of?
Sarcomas
Incl. GIST
Metastatic PrCa with bone mets - treatment:
1.
Prognostic indicators in metastatic BrCa:
Weight loss
Poor performance status
High LDH
(Age<35 worse prognosis in early stage BrCa, but significance unknown in recurrence)
Bevacizumab - MOA
VEGF inhibitor
- used in mCRC
- lung Ca
- paroxysmal nocturnal haemoglobinuria
Denosumab - MOA:
Mab to RANKL –> decreased osteoclastic activity
Aprepitant - MOA
Neurokinin inhibitor (mab)
Tamoxifen - pharmacology:
SERM (selective oestrogen receptor modulator)
Prodrug
Activated by CYP2D6 to Endoxifen.
CYP2D6 competitive antagonists: fluoxetine, paroxetine, sertraline.
Venlafaxine (SNRI) is ok (is used for treatment of hot flushes in SERM therapy).
Citalopram (SSRI) is ok.
Anthracyclines
ACUTE: Arrhythmias, systolic dysfunction, pericarditis. Usually resolves in one week or so.
CHRONIC: Irreversible - within first year after termination, but up to 10 years.
Symptomatic decline in systolic or diastolic dysfunction.
Related to cumulative dose.
NSCLC - which clinical / epidemiological features suggest EGFR mutation?
What does it predict?
Adenocarcinoma
Asian
Non-smoker
Female
–> TKI (erlotinib) responsive
N-staging in NSCLC:
N1: ipsilateral hilar
N2: ipsilateral mediastinal or subcarinal (minimum Stage IIIa)
N3: contralateral mediastinal / hilar OR supraclavicular (minimum Stage IIIb)
NSCLC Stage I or II (operative candidate) –> Pathological Stage III (ie. N2 or higher). Management?
Adjuvant chemotherapy
Not further resection or XRT.
Features suggestive of HNPCC (Lynch syndrome):
…
Extravasation injury - which agents?
Doxorubicin - severe necrosis 4-7 days post.
Vinca alkaloids (Vincristine).
Carcinoid syndrome - clinical features, likely site:
flushing, watery diarrhoea, wheezing.
High 5HIAA.
(Will only be high in carcinoid syndrome, but not just with carcinoids).
Mid-gut tumours (small intestine and proximal colon) - appendix is most common site.
Breast cancer survivors - issues to manage and address:
1. Annual mammography Clinical review 3-6 monthly for 3yrs Then 6-12 monthly for 2yrs Then annually Intensive lab/radiol follow up testing not warranted unless suspicious symptoms (does not improve survival or QoL).
- Minimise risk of further BrCa - avoid HRT; topical oestrogen uncertain - avoid if possible.
- Venlafaxine for hot flushes from hormonal therapy. Avoid SSRIs with tamoxifen (fluoxetine, paroxetine +/- sertraline)
- Osteoporosis screening with DEXA. Esp. With AIs in postmenopausal women. Calcium / vit D, lifestyle. Oral bisphosphonate if progressive bone loss.
Considerations in adjuvant therapy for BrCa - prognostic vs predictive factors (define):
Prognostic factors correlate with outcome without adjuvant therapy (natural history).
Predictive factors correlate with response to certain adjuvant therapies (eg. HER2 overexpression and benefit of Trastuzumab)
Some factors are both prognostic and predictive, eg. HER2 status
Chemotherapy induced nausea and vomiting - mechanisms:
- Stimulation of CTZ (most common):
CTZ-chemothx interaction –> neurotransmitter release (DA, 5HT) –> activation of vomiting centre - Peripheral mechanisms:
(a) damage to GI mucosa
(b) Stimulation of gut neurotransmitter receptors - Cortical mechanisms:
(a) direct cerebral invasion
(b) indirect - psychogenic - Vestibular mechanisms
- Alterations of taste and smell
Types of chemotherapy-associated nausea & vomiting:
Acute: within 24 hours
Delayed: beyond 24 hours
Anticipatory
Risk factors for acute chemo-induced n&v:
- previous chemo-induced ekes is
- alcohol intake is PROTECTIVE
- gender (F>M)
- increasing age
- anxiety, expectation severe ASEs, motivational level
- performance status
- tendency: emesis in pregnancy, previous motion sickness