Oncology Flashcards
1
Q
ECOG 0
A
Fully active, able to carry on all pre disease performance without restriction
2
Q
ECOG 1
A
Restricted physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (light house work, office work)
3
Q
ECOG 2
A
Ambulatory and capable of all selfcare but unable to carry out any work activities. Yp and about more than 50% of waking hours
4
Q
ECOG 3
A
Capable of only limited self care, confined to bed or chair more than 50% of waking hours
5
Q
ECOG 4
A
Completely disabled. Cannot carry on any selfcare. totally confined to bed or chair
6
Q
ECOG 4
A
Dead
7
Q
Best imaging for staging of NSCLC
A
PET-CT if possible
(finds occult LN/distant mets - and higher sensitivity for mediastinal LN)
-Need to get tissue sample of suspicious LN to confirm mets
CT/MRIB for patients who are for curative intent as well
8
Q
Incidence of of different NSCLC histo
A
Adenocarcinoma (approx. 50%),
squamous cell (~20%), adenosquamous
large cell
9
Q
NSCLC - Immunohistochemistry for adeno and SCC
A
Adenocarcinoma: TTF-1, mucin, Napsin-A
Squamous: p63, CK 5/6 (CK 7 neg)
10
Q
NSCLC - Adenocarcinoma molecular characteristics/driver mutations
A
EGFR mutation,
ALK
ROS1 gene rearrangement
11
Q
Tx for Stage 1 NSCLC
A
Essentially. Resect and monitor.
Surgical resection and LN resection for intraoperative staging
VATS preferred
Stereotactic ablative body RTx is alternative for elderly patients or in COPD
12
Q
Tx of Stage 2 NSCLC
A
Resect + Adjuvant chemo
- 2 platinum based drugs:
- Cisplatin/Vinorelbine
- or Carboplatin if cisplatin not tolerated
13
Q
Tx of Stage 3 NSCLC
A
Resect and adjuvant chemo if N0/N1 (hilar LN)
Chemoradiotherapy if N2+ disease, not resectable, or not a surgical candidate
- 6 weeks RTx and concurrent 2 weeks double platinum chemo
- -Cisplatin/Etoposide (superior)
- -Carboplatin-Paclitaxel (less toxic)
Post chemo maintanence:
-PDL1 antibody: Durvalumab (improved survival) - irrespective of PDL1 expression
14
Q
Tx Stage 4 NSCLC
A
Chemo in all stage 4 with EGFR and ALK negative disease and ECOG 0-2
-Improved survival 1.5m and QOL
15
Q
Leading cause of cancer death in australia
A
- Lung cancer
- Prostate
- Breast
- Colorectal
- Pancreas
16
Q
Definition of Stage 1 Lung cancer
A
Parenchymal lesion < 4 cm with no node invovlement
17
Q
Definition of Stage 2 Lung cancer
A
Parenchymal lesion > 4 cm OR smaller lesion with hilar LN
18
Q
Definition of Stage 3 Lung cancer
A
Essentially more than hilar nodes and definitely if any contralateral LN involvement
19
Q
Definition of Stage 4 Lung cancer
A
Any form of mets
20
Q
Cisplatin
A
Platinum based chemo
SE: ototoxicity, Peripheral neuropathy, mephrotoxicity, electrolyte disturbance, myelosuppression, mucositis, partial alopecia
21
Q
Vinorelbine
A
Platinum based chemo
SE: peripheral neuropathy, arthralgia, myalgia, myelosuppression, mucositis, partial alopecia
22
Q
Pancoast tumor and Stage 3 Lung Ca
A
Chemoradiotherapy prior to resection if it is resectable (below N2)
23
Q
Durvalumab
A
Pacific Trial
anti PD-L1
Improved mortality post chemo for NSCLC
24
Q
Anti PD 1 Ab
A
Pembrolizumab
Nivolumab
Bind to PD-1 on T cell
25
Anti PD-L1 Ab
Durvalumab
Atezolizumab
Bind to PD-L1 on Tumor cells
26
Stage 4 SCC lung cancer
Need to know PDL1 status
-If >50% on staining, then treat with Pembrolizumab (tripling survival to 30m)
-If <50% on staining, then Bevacizumab and chemo (mOS 16m)
Chemo choice:
-Cisplatin or Carboplatin plus paclitaxel
27
Approach to Stage 4 Adenocarcinoma Lung cancer
First: Mutation status
- EGFR mutation (10-15%)
- ALK translocation
- ROS1 translocation
Then: if negative to all mutations - PDL1 status and treat with Pembro if >50% staining
28
Clinical phenotype of EGFR mutatnt adenocarcinoma
Asian, light or never smoked, female
29
Stage 4 adenocarinoma EGFR mutation treatment
First and second gen EGFR TKIs
-Erlotinib, gefitinib, afatinib
SE: Rash, diarrhea, nail changes, hair changes, pulmonary toxicity, LFT derrangement
30
Mutation in EGFR mutant adenocarinoma that leads to treatment failure
T790M mutation
31
Tx of EGFR mutant adenocarinoma with T790M mutation
Osimertinib
- 3rd gen TKI resistant to T790M mutation
- Increased mOS and better brain activity
If no T790M mutation
-Chemo/Bev/IT/Clincial trial
32
NSCLC ALK mutation phenotype
Light/never smoked
younger age
Adenocarinoma with acinar or signet ring histo
Need FISH testing for confirming
33
Stage 4 adenocarinoma ALK Translocation treatment
1st Line: Alectinib
SE: myalgia, constipation, oedema, photosensitivity, bradycardia
2nd line: Crizotinib
SE: vision disorders, N+D, oedema
34
Stage 4 adenocarinoma ROS1 Translocation treatment
Crizotinib
35
KRAS mutatons in NSCLC
20-25%
Commonly detected
Not targetable yet
Treat as per wild type tumors
36
Tx of Stage 4 Adenocarcinoma without driver mutation
PDL1 >50%
-Pembro
PDL1 <50%
Bevacizumab +chemo (cisplatin/carboplatin +pemetrexed or paclitaxel)
37
Definition Limited Stage SCLC
Ipsilateral hemithorax and regional nodes
38
Definition Extensive Stage SCLC
Disease on contralateral nodes/distant mets
39
Tx limited stage SCLC
Chemoradiotherapy (platinum/etopiside)
+Prophylactic cranial irradiation (improves survival)
40
Tx Extensive stage SCLC
Chemoradiotherapy (platinum/etopiside)
+Atezolizumab (improves 2 month survival)
+Thoracic radiation if residual disease (improves survival)
+Prophylactic cranial irradiation in select patient (contraversial)
41
Paraneoplastic Syndromes associated with which cancer: Hypercalcemia
Squamous cell cancer
| -PTHrP release by tumor
42
Paraneoplastic Syndromes associated with which cancer: SIADH and Neurologic syndromes
Small Cell Lung cancer
Neuro: Lambert eaton syn, cerenellar ataxia, sensory neuroapathies
43
Risk factors for breast cancer
- Early menarche/late menopause
- Nulliparity/increased age first pregnancy
- Proliferative type benign breast disease
- Family/PHx
- Genetic mutations
- HRT
- Weight (increased postM, low preM
- Ionising radiation
Breast feeding and physical activity is protective
44
Most common type of breast cancer
Invasive carcinoma NST (80%)
45
Invasive lobular carcinoma (Breast cancer) features
More likely to be bilateral or multicentric
Lower grade and ER+
Unusual mets (GI, peritoneum, meninges)
46
Bad subtype of Breast cancer
Micropapillary
47
Breast Cancer: Stage 1
Small and node negative
48
Breast Cancer: Stage 2
Large and/or <4LN
49
Breast Cancer: Stage 3
Infamm or chest wall and/or >4LN
50
Breast Cancer: Stage 4
Metastatic
51
Inflammatory breast cancer features
Diffuse erythema/oedema (peau d'orange) of >1/3 of breast skin, lymphoedema caused by tumor emboli in dermal lymphatics
52
Surgery for early breast cancer (Stage 1-3)
Primary Cancer
- Wide local excision
- Mastectomy if multicentric, high tumor:breast ratio, risk reduction, or CI to RTx
Nodes
- Clinically node negative - sentinal LN Bx
- Clinically node positive then Axillary clearance
53
Radiation for early breast cancer (Stage 1-3)
Reduction in local recurrence and breast cancer deaths
Would do after mastectomy if node positive, large tumor >5 cm, or multiple high risk features
54
Strongest prognostic factor in Breast cancer
LN involvement
55
Definition of Neoadjuvant chemotherapy and role in breast cancer
Chemo before surgery
- Can decrease size and make cancer resectable
- Can aid in assessing if patient gets complete pathological response, if not can change treatment used in adjuvant setting
56
Role for Bisphosphonates in Breast Cancer Mx
Zolindronic and pomindronate adn denosumab
-Improve survival in post menopausal or OFS population if given for 3 years
57
Mx ER positive EARLY Breast Ca and prognosis
Low Risk: Endocrine therapy
- PreM: Tamoxifen OR OFS+AI if high risk
- PostM: AI, but can trial tamoxifen (inferior)
High Risk: Chemo (taxane and anthracycline) then Endocrine therapy
Good prognosis, but late recurrence > 5 yrs can occur
58
Mx HER positive EARLY Breast Ca and prognosis
Trastuzumab 52 weeks + Chemo (anthracycline +Taxane)
-If High risk: Consider adding other HER2 agents (pertuzumab, neratinib)
Good prognosis due to treatment
59
Mx Triple negative EARLY Breast Ca and prognosis
Chemotherapy
-Anthracycline +Taxane
Poorest prognosis, but late recurrences >5 years are uncommon
60
Endocrine Therapy in Breast Cancer (Premenopausal)
Ovarian function suppression + aromatase inhibitor is best for 5 years
Can use tamoxifen alone for 10 years, but inferior
61
Endocrine Therapy in Breast Cancer
| Post menopausal
Aromatase inhibitors are best
Tamoxifen is an option if CI or intolerant
62
Tamoxifen MOA
Selective estrogen receptor modulator
- Anti-estrogenic: Breast
- Pro-estrogenic: Bones (partial), uterus
63
Tamoxifen SE
```
Hot flushes
VTE (2-3x)
Uterine cancer
Cataracts
NAFLD
```
64
Mx of hot flushes on Tamoxifen
stay cool, avoid cheese, wine, and chocolate
Gabapentin
Venlafaxine
65
MOA Aromatase inhibitors and Names
Inhibit peripheral conversion of androgen to estrogen
-Not suitable in PreM unless OFS
Anastrozole, letrozole
66
Aromatase inhibitor side effects
Hot flushes
Accelerated BMD loss
AIMSS: joint pain and stiffness (hands mainly)
Vaginal dryness
More CVD, high chol, DM compared to
Tamoxifen
If used in premenopausal women without OFS can cause increase in estrogen levels
67
Chemotherapy classes used in breast cancer
Anthracyclines (epirubicin/doxorubicin)
| Taxanes (Paclitaxel/docetaxel)
68
Anthracyclines SE
```
Cardiotoxicity - irreversible
ORange urine
Alopecia
myelosuppression
mucositis
N+V
Fatigue
Amenorrhea (risk increases with age)
Risk of secondary leukemia
```
69
Taxanes SE:
```
Peripheral neuropathy
Fluid retention
Infusion reaction
nail changes
Alopecia
myelosuppression
mucositis
N+V +D
Fatigue
Amenorrhea (risk related to age)
```
70
Trastuzumab MOA
Monoclonal Ab that binds to Her2
| Inhibits proliferation and survival
71
Trastuzumab SE
```
Cardiac Dysfunction (10% drop LVEF)
-Reversible myocyte stunning
```
RF: Age >60, Chest RTx, Anthracycline use, high dose cyclophosphamide, HTN, known CAD
72
Tx of ER positive metastatic breast ca
Endocrine therapy is FIRST line
-unless highly symptomatic and high volume visceral disease
PreM:
- OFS w/ GnRH analogue +AI +CDK 4/6 inhibitor
- OR Tamoxifen alone
PostM: AI + CDK 4/6
+Chemo - single agent first
PI3-kinase inhibitor (causes proliferation -oncogenes)
73
CDK 4/6 inhibitor
Ribociclib, palbociclib, abemaciclib
Inhibit progress of of cell from G to S phase
Improve overall survival in Breast Ca
SE: reversible neutropenia, LFT derrangement, QT prolongation
74
Tx of HER2 postive metastatic Breast Cancer
Trastuzumab/pertuzumab/taxane chemo
Second line:
- T-DM1 (drug antibody conjugate -trastuzumab and emtansine)
- SE: thrombocytopenia, liver toxicity
75
Tx of triple negative metastatic breast cancer
Atezolizumab + Taxane
- PARP inhibitors after chemo if BRCA mutant
- Carboplatin if BRCA mutant
76
Role for Bone modifying agents in metastatic Breast cancer
First line: Denosumab
- Decrease time to first/prevalence of skeletal related events
- -Fracture, need for surgery/RTx, spinal cord compression, hypercalcemia
-Improve bone pain
DO NOT IMPROVE SURVIVAL
77
BRCA1/2 phenotype
younger age of cancer
| Triple negative subtype with BRCA 1
78
Who to do BRCA testing in
- Relative who is positive
- High grade ovarian cancer
- Triple neg Breast Ca and age <50
- Male with breast ca
- 2 primary Breast ca and one <50yo
- Breast Ca and age <40
- 2 first/second degree relatives +breast ca <50, jewish, male breast ca
79
BRCA gene positive: Ovarian screening
Nil screening program
BSO by age 45 to exclude occult malignancy
80
BRCA gene positive:
| Breast Screening
Prophylactic bilateral mastectomy by 40
30-40 yo: annual MRI +/- US
40-50 yo: annual MRI +/- MMG +/- US
>50 yo annual MMG+/- US
81
WHO Criteria for screening test
- Important health problem
- Recognisable latent or early symptomatic stage
- Natural Hx understood
- Tx available for disease
- Test/examination has high accuracy
- Cost effective
82
Lead time bias
LEngth of time by which diagnosis advanced by screening
| -Will length time between diagnosis and death independent of intervention
83
Length time bias
More indolent tumors have a longer latent period
- More likely to be screen detected
- Artificial advantage to screen detected cases
84
Breast Cancer Screening Program
| Low risk
Women 50-74 yo have MMG every 2 years
85
Breast Cancer Screening Program
| Mod risk
One 1st degree relative diagnosed <50 yo OR two 2nd degree <50 yo
-Start at age 40, consider annual MMG
Two 2nd degree relatives >50 yo
-Annual MMG
86
Breast Cancer Screening Program
| High risk
Two first degree or second degree relatives with breast or ovarian cancer plus
- other relatives
- Breast Ca <50yo
- Relative with >1 BC or ovarian cancer
- Jewish
- Male breast ca
Refer to familial cancer clinic
87
Cervical Cancer Screening
Age 25-74
Every 5 years
1. No HPV - Repeat in 5 years
2. HPV non 16/18 detected, no abnormal cells - Repeat in one year
3. HP non 16/18 and abnormal cells OR HPB 16/18 detected - Refer for colposcopy
4. Unsatisfactory sample: retest 6-12 weeks
88
```
Bowel Cancer screening
General population (5-10% risk)
```
iFOBT every 2 years from 50-74 yo
Generally:
-Start at 50yo or 10 yr prior to FDR diagnosis
89
Bowel Cancer Screening
| (Mod Risk) 15-30% risk
- One FDR <55 yo
- Two FDR at any age
- One FDR and >one SDR at any age
iFOBT every 2 years from 40-49 AND Colonoscopy every 5 years from 50-75 yo
90
Bowel Cancer Screening
| (High Risk) 30-40% risk
- Three FDR at any age
- Three FDR or SDR, one diagnosed <55 yo
iFOBT every 2 years from 35-44yo AND Colonscopy every 5 years 45-74 yo
91
Types of ovarian cancer
- High grade serous (most common - from distal fallopian tube)
- mucinous invasive (GI source)
- Endometroid (endometrial source)
- Clear cell ( endometrial source)
92
Reccomendation for testing for women <70 with high grade non-mucinous epithelial ovarian, fallopian tube, or primary peritoneal cancer
REferral for BRCA1/2 testing
93
Which BRCA gene is associated with better ovarian outcomes
BRCA2
94
What stage does ovarian cancer present at
Stage 3 and 4
| -Due to non specific symptoms of early stages
95
Tx of Ovarian cancer
Debulking surgery + Adjuvant chemo
+Bevacizumab (stage 3 and 4)
+PARPi if BRCA +ve (maintainence)
(Neoadjuvant can be done if +++Symptoms)
-Carboplatin + Paclitaxel
(15-16 mo PFS)
96
Recurrence rate post initial Tx for ovarian cancer and outcome
80%
- Platinum sensitive (present >6 mo post chemo) Have 2nd remission post chemo before possible recurrence and progression
- Platinum resistant (present <6 mo post chemo) - Progress :(
97
Role for intraperitoneal chemo in Ovarian Ca
Contraversial, but first line option
| -MAny patients cease early due to toxicity and worse QOL
98
Synthetic lethality
Refers to the ability of PARP inhibitors to selectively kill tumor cells that have BRCA mutations because they are unable to repair DNA damage
99
PARP inhibitors
Olaparib
Niraparib
Rucaparib
Used in BRCA positive metastatic breast cancer
100
Role for CA-125 in monitoring for recurrence of ovarian Ca
not recommended
101
Most common gynecological malignancy
Endometrial cancer
- Due to increasing rates of obesity and metabolic syndrome
- Median age of diagnosis 63
102
Risk factors for endometrial cancer
- Unopposed estrogen
- Obesity
- PCOS
- Tamoxifen use
- Nulliparity
- Age
- Lynch Syndrome
OCP is protective
103
Type 1 endometrial cancer
Most common (80%)
- Adenocarcinomas
- estrogen dependent
- Good prognosis
104
Type 2 endometrial cancer
- High grade endometriod, serous, or clear cell
- Estrogen independent
- Poor prognosis
105
Tx of endometrial cancer
Surgery is main stay
-Total hysterectomy and BSO +/- LN sampling
Low risk: Monitor post
Intermediate: +RTx
High: RTx +/- chemo Carboplatin+Paclitaxel)
Consider Hormone therapy if ER/PR Positive
Evidence for PDL1 inhibitors if mismatch repair genes present (MSI high)
106
Early Cervical Cancer Treatment
Surgical for small lesions
| +/- adjuvant chemoradiation if high risk features (Cisplatin)
107
Advanced Cervical Cancer tx
Incurable, survival year
- Bevacizumab + Carboplatin +Paclitaxel
- Consider palliative RTx
108
Method of inheritance of cancer predisposition genes
AD with incomplete penetrance
109
BRCA Gene function
part of a complex that repairs double strand breaks in DNA via the homologous recombination pathway and maintains genomic stability (Tumor suppressor genes)
110
BRCA 1 Breast cancer pathology
- Medullary carcinoma more common
- Grade: High mitotic count, pleomorphic, high tubule
- Triple negative usually
- Ovarian: High grade serous adenocarcinomas
111
BRCA2 Breast cancer pathology
- Grade: lack tubules and lower mitotic counts
| - ER/PR not significantly different in proportion to general population
112
RANK L in BRCA breast cancer
May be a role for denosumab in the future to inhibit RANKL
113
Spontaneous CRC vs Lynch - most common gene affected
MLH1 methylation
114
BRAF V600E mutation
Seen in Sporadic CRC not Lynch
115
Pembrolizumab in MMR deficient CRC
Shown to improve outcomes in CRC that is MMR deficient - not on PBS
116
Lynch Syndrome Genetic inheritance
AD, heterozygous germline mutation in MMR genes
| -MLH1, MSH2, MSH6, PMS2, EPCAM (silences MSH2)
117
Loss of what genes more so associated with Lynch
MSH2 and MSH6
118
Loss of what genes more so associated with sporadic CRC
Loss of MLH1 and BRAF positive
If MSI not high and BRAF positive - very very aggressive cancer
119
Cell cycle: Transition between stages is regulated by what?
CDK - Cell Dependent Kinases
120
Alkylating Agents: Subclasses and names
Mustards:
-Cyclosporin, cyclophosphamide, chlorambucil, Dacarbazine, Temozolomide, Lomustine, Streptozotocin
Platinums:
-Cisplatin, Carboplatin, Oxaliplatin
121
Alkylating Agents MOA
Cell cycle non specific
"Alkylates" guanine, distorts DNA structure, repair enzymes fail
Prevents helicase from seperating dsDNA and prevents replication
122
Antimetabolites: Subclasses and names
Purine antagonists (A,G)
- Fludarabine, 6-mercaptopurine, 6-thioguanine
- MTX
Pyramidine antagonist (T,C)
- Fluoropyrimidines (5-FU, capecitabine, S-1, TAS-102)
- Gemcitabine
123
Antimetabolites MOA
Work by interfering with T G C A
| Interfere with DNA and RNA production
124
Role for DPD in 5-FU metabolism
it breaks down 5-FU, so if deficienct will get toxicity
| Capecitabine is a prodrug of 5-FU (longer half life)
125
Ankaloids: Vinca - Names and MOA
-Vincristine, vinblastine, vinorelbine
Bind to tubulin, stop microtubulin formation
126
Ankaloids: Taxanes - Names and MOA
Paclitaxel, Docetaxel
- Binds to tubulins
- Stops microtubule disassembly
127
Ankaloids: Camptothecins - Names and MOA
Irinotecan, topotecan, etoposide
-Topoisomerase inhibiters - Cause DNA tensioning during S phase, so cannot replicate (S phase specific)
128
Anthracyclins - Names and MOA
Doxorubicin, Daunoribicin, Epirubicin, Mitoxantrone
- From strepmyces bacteria (antibiotic)
- Non cell cycle specific, interfere with Topoisomerase 2, metabolite is a free radical causing widespread damage
- Induces histone eviction from chromatin
129
LHRH analogues
Lucrin, Zoladex (Goserelin)
130
-omab
mouse
131
-uximab
chimeric
132
-uzumab
humanised
133
-umumab
fully human
134
CRC CIMP Phenotype
Right sided CRC
Older patients
Arise in "Serrated" adenoma
135
FAP inheritance and phenotype
AD, 90% penetrance
Virtually all develop CRC by 40
APC gene as germ line mutation (tumor suppressor)
-25% have on FHx
- Associated Ca
- -papillary thyroid, ileal carcinoid, gastric cancer
136
Amsterdam criteria
For HNPCC
- 3 cases
- 2 generations
- 1 <50 yo - either CRC or related cancer
137
CRC number of adequate LN needed during resection
>12
138
Lynch Syndrome associated cancers
```
Endometrial ca
Ovarian
Gastric/SB/ hepatic
Brain
Renal
```
139
Lynch Syndrome screening
At risk family members:
| Annual or 2 yearly Cscope from age 25 or 5 years prior to earliest age of cancer Dx in family
140
FAP screening
Start yearly flexi sig/Cscope age 10-12
Likely will need colectomy in teens or early 20s
141
MUTYH associated polyposis
AR
Biallelic mutation in MUTYH gene
Polyposis by age 50-60
CRC risk 70-75%
142
Aspirin and CRC
Shown to have reduced the incidence of CRC
- Delayed benefit after 5 years
- Thought to be via COX 2 inhibition which is expressed in CRC
143
Tx of Stage 1 CRC
| T1/T2 N0
Surgery alone
144
Tx of Stage 2 CRC
| T3/T4 N0
```
Surgery
+Adjuvant chemo if high risk features: (5-FU or Capecitabine)
-T4 tumor
Perforation/obstruction
-Lymphovascular invasion
-Poorly differentiated
-Inadequate LN samples
-High pre op CEA?
-MSI normal (stable)
```
145
Tx of Stage 3 CRC
| any T and N1/N2
Surgery + Adjuvant chemo
- 6 months FOLFOX (Folic acid, 5-FU, Oxaliplatin)
- IF low risk (N1) can do 3 months CAPOX (Capecitabine, Oxaliplatin)
146
Tx of locally advanced rectal cancer
MRI for staging
Neoadjuvant chemoradiation
(5FU or Capcitabine)
Post op adjuvant chemotherapy dependent on histo and response to neoadjuvant and if node positive
147
Tx of low rectal cancer <6 cm from anal verge
Not able to be resected
| Neoadjuvant chemoradiation
148
Surveillance after early stage colon cancer
First 2 years:
-3 monthly CEA + 6 monthly CT CAP
Year 3-5:
-6 monthly CEA and annual CT
Colonoscopy at anniversary and then second yearly
149
Tx of metastatic CRC
| -Group 1: Resectable mets
Aim to cure.
- Surgery and adjuvant chemo
- Can do neoadjuvant chemo if borderline resectable
150
Tx of metastatic CRC
| -Group 2: Unresectable and high tumor burden
Not curable
Chemo +/- targeted therapy
- FOLFOX or FOLFIRI (Folinic acid, 5-FU, Irinotecan)
- Trifluridine/Tipiracil (Lonsurf) - new alt to 5-FU - last line therapy (refractory CRC)
-Targeted:
--Bevacizumab (VEGF) (right side)
If KRAS wild type:
--Cetuximab (left sided CRC) or Panitumumab
(EGFR)
-If MSI High - Role for PDL1 inhibitor, but not on PBS
151
Sister Mary Joseph Nodule
Gastric mets to umbilical area
152
Virchow's node
Gastric met to left supraclavicular LN
153
Mx of Gastric CAncer Stage 1-3
Stage 1 - resect
Stage 2/3 Neoadjuvant chemo, resection, and follow up chemo
Consdier radical gastrectomy up to stage 3
FLOT4
(Docetaxel, 5-FU, Leucovorin, oxaliplatin)
154
Mx of stage 4 gastric cancer
Platinum based chemo
(Docetaxel/cisplatin/5FU)
+Irinotecan
PD1 therapy in dMMR/MSI high (Pembro)
If HER2 positive, can also add trastuzumab
155
GIST Diagnosis
"mesenchymal" tumor
-connective tissue/smooth muccle tissue
C-kit positive
CD117
Spindle shaped cells
Rx: Imatinib
156
Role for pre-operative portal vein embolisation in Cholangiocarcinoma
to increase the limits of safe hepatic resection (induces lobar hypertrophy)
157
Tx of Cholangiocarcinoma
Surgery is only cure.
Adjuvant chemo:
-Capecitabine
Palliative Chemo:
-Gemcitabine/Cisplatin
158
Tx of Pancreatic cancer
Surgery +Adjuvant chemo
| mFOLFIRINOX
5FU, oxaliplatin, leucovorin, irinotecan
159
Definition of castration resistant prostate cancer
Prostate cancer growth despite castrate levels of testosterone (<1.7 nmol/L)
160
Mx of metastatic castration sensitive prostate cancer
ADT (androgen deprivation therapy) +Docetaxel if high volume cancer
- GnRH agonists (goserelin, leuprolide)
- GNRH antagonist (degarelix) - avoids flare response
161
What is the flare response associated with ADT in prostate cancer
Initial surg of testosterone when GnRH agonist is given that may worsen cancer and symptoms
162
Mx of castration resistant prostate cancer
Chemo
-Docetaxel or Cabazitaxel
Androgen receptor targeted therapy
- Abiratone (inhibts 17 alpha hydroxylase and given with pred 10 mg daily)
- Enzalutamide (CI in seizures)
Role for PARP inhibitors too if DNA repair abnormalities
163
Docetaxel SE
sensory/motor PN, cytopenias (neutropenic sepsis), hypersensitivity reactions
164
Cabazitaxel SE
diarrhoea, cytopenias, sensory/motor PN (less common than D), less alopecia
165
Fleischner Criteria
Single:
<6mm: low risk - no f/u
<6 mm high risk- CT 1yr
6-8mm: low or high risk - CT 6-12 mo
>8 mm: low or high risk - CT/PET/tissue in 3 mo
Multiple:
<6mm - low: no f/u
<6mm - high: CT 1 yr
6-8mm or >8 mm and low or high risk: CT 306 mo
166
Ki-67
marker of cell proliferation
167
Which tumor marker goes up with smoking
CEA
168
Which cancer is obesity a greatest risk factor in
endometrial
169
Abitaterone MOA and SE
17 alpha hydroxylase inhibitor
SE:
-HTN, Hypokalemia, peripheral oedema, tranaminitis
Give with pred to reduce SE
170
PSMA (prostate specific mebrane antigen)
Overexpressed in prostate cancer.
| Possible use in future targeted disease treatment
171
Most common renal cell cancer
Clear cell
172
Role of VHL protein in Renal cell cancer
VHL keeps HIF in check
HIF promotes angiogenesis, cell proliferation
VHL mutation leads to excessive HIF with promites carcinogenesis
173
Poor prognostic signs in Renal cell cancer
High ECOG
Hypercalcemia
Low Hb
High LDH and Plt
174
Mx of renal cell cancer
1st: TKI
- Sunitinib or Pazopanib
2nd: Nivolumab, Sorafenib, atixinib
3rd: Everolimus
175
Most common bladder cancer in developed countries
Transitional cell carcinoma (urothelial)
176
Treatment of muscle invasive bladder cancer
Neoadjuvant chemo improved survival
(Cisplatin+gemcitabine)
Radical cystectomy preferred, but alternative is chemoradiation
2nd line: PD1/PDL1 - not PBS approved
177
Differentiating seminoma vs non seminoma testicular cancer
AFP NOT produced by pure seminoma
BHCG and LDH can be produced by both
178
Mx of seminoma testicular cancer
Carboplatin only
Risk of recurrence if tumor >4 cm or rete testis invasion
179
Mx of non-seminoma testicular cancer
BEP
| Bleomycin, etopiside, cisplatin
180
Prognostication factors of melanoma
1. Tumor thickness
2. Mitotic rate
Ulceration, older age, male, LN involvement, location
LDH
181
Mx of stage 1 melanoma
resect and consider sentinal LN Bx if >1mm or high risk features
182
Mx of stage 2 melanoma
Resect + Sentinal LNBx +Adjuvant RTx +/- systemic Tx
183
Mx of stage 3 melanoma
| LN involvement
Resect + Nodal dissection + Adjuvant RTx +/- systemic Tx
184
Mx of stage 4 melanoma
BRAF mutation:
- 1st line: BRAF +MEK inhibitor
- 2nd line: Ipilimumab +Nivolumab
No BRAF mutation:
-1st Line: Ipilimumab +Nivolumab
185
BRAF Mutations in Melanoma
More common in little chronic skin exposure, younger patients
80% BRAF V600E
5-30% BRAF V600K
186
BRAF inhibitors names, MOA, and SE
Vemurafenib, Dabrafenib
Attach to mutant BRAF V600. BRAF results in downstream activation of MEK and ERK with leads to uncontrolled cell proliferation. This is ceased.
SE: fevers, tachycardia, diarrhea, rash and pruritis, SCCs
187
Complication with only BRAF inhibitor use in melanoma
Cx: 80% pts develop resistance via the MAPK reactivation through MEK (prevented by combo MEK and BRAF inhibitor)
188
MEK inhibitors
Cobimetinib, Trametinib
MOA: Inhibition of downstream MAPK pathway
Decreases side effects from BRAF inhibitors alone
SE: photosenitivity
189
Which drug is most associated with pseudoprogression
CTLA 4 inhibitor
| Ipilimumab
190
When is the peak time of immunotoxicity with immunotherapy and which drugs are most likely the cculprit
first 3 months, but can occur anytime
Ipi/Nivo>Ipi>Nivo
191
Mx of Brain mets in Breast cancer
Resection if possible or stereotactic RTx
| -Stereotactic done if <5 mets, otherwise have to do whole brain RTx
192
At what size of mass are PET scans not helpful
<1 cm
| If cold on PET scan, then still cannot rule out cancer
193
Common immune related AEs
```
AI colitis
AI dermatitis
AI hepatitis
AI hypophysitis
-p/w fatigue, headache, nausea
-Adrenal insufficiency, hypo/hyperthyroidism, or hypogonadism
Pneumonitis
-Non productive cough and dyspnea
```
Generally:
-Rash first, then diarrhea, then liver and hypohysitis later
194
Mx of IRAEs
Grade 1: Mild
-Symptomatic (loperimide for colitis, topical steroid for rash)
Grade 2: Mod
-PO steroid
Grade 3: Hospital
-IV Steroids
Grade 4: Severe
-IV steroid + other immunosuppressant
195
Breast cancer Brain met - receptor status?
HER2 +ve
196
Breast cancer Bone and LN mets - receptor status?
ER/PR positive
197
PSMA scan
PET scan with prostate specific membrane antigen enabling better detection of mets
Highly sensitive and specific
198
Prostate cancer: Role for denosumab and zolendronic acid
REduce skeletal related events in castrate resistant bony mets
