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GCUH FRACP Writtens 2020 > Medical Oncology > Flashcards

Medical Oncology Flashcards

1
Q

What malignancy and manifestations is antibody Hu associated with?

A

Small cell lung cancer

Limbic encephalitis, peripheral neuropathy

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2
Q

What malignancy and manifestations is antibody Yo associated with?

A

Breast / Ovarian Ca

Cerebellar degeneration

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3
Q

What malignancy and manifestations is antibody Ri associated with?

A

Small cell lung cancer

Opsoclonus myoclonus, rhomboencephalitis

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4
Q

What malignancy and manifestations is antibody Ma/Ta associated with?

A

Testicular cancer

Rhomboencephalitis

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5
Q

Which malignancies is H Pylori associated with?

A

Gastric cancer

MALT lymphoma

Mechanism is chronic inflammation

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6
Q

Which cancers is HPV implicated in?

A

Cervical cancer

Vulval cancer

Vaginal cancer

Penile cancer

Anal cancer

Oropharyngeal cancer

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7
Q

Which genes are involved in the pathogenesis of Lynch syndrome?

A

MLH1

MSH2

MSH6

PMS2

EPCAM

MLH1 and PMS2 co-associated

MSH2 and MSH6 co-associated

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8
Q

Name 5 different classes of chemotherapy.

A

Alkylating agents - e.g. platinum-based, mustard-based

Anti-metabolites - anti-folates, purine and pyramidine analogues

Alkaloids - microtubule and topoisomerase poisons

Antibiotics

Hormones

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9
Q

Name 6 different alkylating agents.

A

Mustard and derivatives

  • cyclosporin
  • cyclophosphamide
  • chlorambucil
  • temozolamide

Platinum agents

  • cisplatin
  • carboplatin
  • oxaliplatin
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10
Q

What is the mechanism of action of alkylating chemotherapy agents?

A

Non-cell cycle specific

“Alkylates” guanine, distorting DNA structure; repair enzymes fail and fragment DNA

Cross-links DNA forming strong bond preventing helicase separating double strand, preventing replication

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11
Q

Name 5 examples of anti-metabolite chemotherapy.

A

Purine antagonists (adenine, guanine)

  • fludarabine
  • 6MP
  • methotrexate

Pyramidine antagonists (thymine, cytosine, uracil)

  • 5FU
  • gemcitabine
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12
Q

Name 6 different alkylating agents.

A

Mustard and derivatives

  • cyclosporin
  • cyclophosphamide
  • chlorambucil
  • temozolamide

Platinum agents

  • cisplatin
  • carboplatin
  • oxaliplatin
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13
Q

Name 5 different classes of chemotherapy.

A

Alkylating agents - e.g. platinum-based, mustard-based

Anti-metabolites - anti-folates, purine and pyramidine analogues

Alkaloids - microtubule and topoisomerase poisons

Antibiotics

Hormones

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14
Q

Name 5 examples of anti-metabolite chemotherapy.

A

Purine antagonists (adenine, guanine)

  • fludarabine
  • 6MP
  • methotrexate

Pyramidine antagonists (thymine, cytosine, uracil)

  • 5FU
  • gemcitabine
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15
Q

How do alkaloids work?

A

Vinca alkaloids - bind to tubulin and stop microtubule formation

Taxanes - bind to tubulin and stop microtubule disassembly

Topoisomerase inhibitor - DNA “tensioning” - S phase specific

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16
Q

Name 7 examples of alkaloids.

A

Vinca alkaloids

  • vincristine
  • vinblastine
  • vinorelbine

Taxanes

  • paclitaxel
  • docetaxel

Topoisomerase inhibitors

  • Irinotecan
  • etoposide
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17
Q

Name 5 examples of antibiotic-based chemotherapies.

A

Doxorubicin

Daunorubicin

Epirubicin

Mitoxantrone

These are anthracyclines derived from streptomyces bacteria

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18
Q

How do alkaloids work?

A

Vinca alkaloids - bind to tubulin and stop microtubule formation

Taxanes - bind to tubulin and stop microtubule disassembly

Topoisomerase inhibitor - DNA “tensioning” - S phase specific

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19
Q

Name 7 examples of alkaloids.

A

Vinca alkaloids

  • vincristine
  • vinblastine
  • vinorelbine

Taxanes

  • paclitaxel
  • docetaxel

Topoisomerase inhibitors

  • Irinotecan
  • etoposide
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20
Q

Name 5 examples of antibiotic-based chemotherapies.

A

Doxorubicin

Daunorubicin

Epirubicin

Mitoxantrone

These are anthracyclines derived from streptomyces bacteria; non-cell cycle specific; interferes with topoisomerase 2

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21
Q

How do anthracycline chemotherapies work?

A

Interferes with topoisomerase 2

Metabolite is a free radical causing widespread damage

Non-cell cycle specific

Induces histone eviction from chromatin

…definitely not to treat infections

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22
Q

Name 6 classes of hormone-based chemotherapy.

A

LHRH analogues e.g. lucrin, Zoladex

Selective Oestrogen Receptor Modulator (SERM) e.g. tamoxifen

Aromatase inhibitors e.g. anastrozole, letrozole

Steroidal aromatase inhibitors e.g. exemestane

Peripheral androgen blockers e.g. bicalutamide, glutamine

Adrenal androgen synthesis e.g. abiraterone

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23
Q

How does obesity impact upon the chance of developing pre-menopausal and post-menopausal breast cancer?

A

Obesity decreases the chance of developing pre-menopausal breast cancer

Obesity increases the chance of develop post-menopausal breast cancer

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24
Q

Which gene is deleted in Familial Adenomatous Polyposis?

A

Deleted APC gene as germ-like mutation

25% have no family history

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25
Q

Which cancers may be seen in conjunction with FAP besides colorectal cancer?

A

Papillary thyroid

Ileal carcinoid

Gastric cancer

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26
Q

What is the Amsterdam criteria for Lynch syndrome?

A

“3-2-1 rule”

3 affected members

2 generations

1 under age 50

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27
Q

What features would suggest that a stage 2 colorectal cancer might be “high risk”? Name 4.

A

Obstruction

Poor differentiation

Extramural venous invasion

Adjacent organ invasion

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28
Q

What is the treatment for stage 2colorectal cancer?

A

Surgery cures 80% of cases

3-6 months adjuvant chemo for high risk stage 2 (5FU)

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29
Q

Which cancers may be seen in conjunction with FAP besides colorectal cancer?

A

Papillary thyroid

Ileal carcinoid

Gastric cancer

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30
Q

What is the Amsterdam criteria for Lynch syndrome?

A

“3-2-1 rule”

3 affected members

2 generations

1 under age 50

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31
Q

What features would suggest that a stage 2 colorectal cancer might be “high risk”? Name 4.

A

Obstruction

Poor differentiation

Extramural venous invasion

Adjacent organ invasion

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32
Q

What is the treatment for colorectal cancer?

A

Surgery

3-6 months adjuvant chemo for high risk stage 2 and stage 3

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33
Q

What is the treatment for colorectal cancer?

A

Surgery

3-6 months adjuvant chemo for high risk stage 2 and stage 3

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34
Q

What is the treatment for stage 3 colorectal cancer?

A

Stage 3, any T, N1/2 - surgery + 6 months adjuvant FOLFOX

T3/4 or node positive disease in rectal - XRT too (5FU is sensitiser)

If resectable mets - aim to cure

If unresectable - chemo (FOLFOX/FOLFIRI) + targeted therapy

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35
Q

What is bevacizumab, how does it work and what adverse effects does it have?

A

Mono Ab - binds and inhibits VEGF

Hypertension

Proteinuria

GI perforation

Thromboembolic events

Delayed wound healing

Can be used regardless of RAS/RAF status and location of tumour

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36
Q

What is bevacizumab, how does it work and what adverse effects does it have?

A

Mono Ab - binds and inhibits VEGF

Hypertension

Proteinuria

GI perforation

Thromboembolic events

Delayed wound healing

Can be used regardless of RAS/RAF status and location of tumour

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37
Q

What is cetuximab, how does it work and what are its side effects?

A

Mono Ab - anti-EGFR (EGFR -> RAS -> RAF -> MAPK)

Indicated in KRAS/RAF wild type (50% of CRC)

Rash (correlates with activity)

Skin sensitivity

Diarrhoea

Renal salt wasting

Worse toxicity in combination with capecitabine

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38
Q

What is cetuximab, how does it work and what are its side effects?

A

Mono Ab - anti-EGFR (EGFR -> RAS -> RAF -> MAPK)

Indicated in KRAS/RAF wild type (50% of CRC)

Rash (correlates with activity)

Skin sensitivity

Diarrhoea

Renal salt wasting

Worse toxicity in combination with capecitabine

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39
Q

What is trifluridine/tiperacil (Lonsurf)?

A

Nucleoside analogue and thymidine phosphorylase inhibitor

Works differently to 5-FU based fluoropyrimidines for CRC

SE - neutropenia

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40
Q

With GIST, what positive maker would you expect to see?

A

CD117 positive in 50% of cases (C-kit positive)

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41
Q

What sort of cells do you expect to see with GIST on histopath?

A

Spindle shaped cells

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42
Q

How are GISTs treated?

A

Imatinib

If PD - escalate doses (800mg daily max), then sunitinib and regorafenib

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43
Q

As well as a hypervascular liver lesion, what sort of AFP level would you expect to see in patients you suspect of HCC?

A

AFP >400

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44
Q

What is the main cause of HCC in Australia?

A

Viral hepatitis infection

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45
Q

What is the Barcelona Criteria for HCC and how does it influence treatment?

A

Stage 0 - single <2cm lesion, carcinoma in situ - resect/transplant

Stage A-B (multiple nodules, CPA or B) - chemoembolisation

Stage C - advanced(portal invasion) - TKIs

Stage D - terminal - (mets) - symptomatic

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46
Q

How is prostate Ca treated?

A

Organ confined - radical prostatectomy comparable to radical radiotherapy

Neo-adjuvant and adjuvant hormones for higher risk tumours treated with radiotherapy

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47
Q

What is the Barcelona Criteria for HCC and how does it influence treatment?

A

Stage 0 - single <2cm lesion, carcinoma in situ - resect/transplant

Stage A-B (multiple nodules, CPA or B) - chemoembolisation

Stage C - advanced(portal invasion) - TKIs

Stage D - terminal - (mets) - symptomatic

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48
Q

What is the main cause of HCC in Australia?

A

Viral hepatitis infection

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49
Q

As well as a hypervascular liver lesion, what sort of AFP level would you expect to see in patients you suspect of HCC?

A

AFP >400

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50
Q

How are GISTs treated?

A

Imatinib

If PD - escalate doses (800mg daily max), then sunitinib and regorafenib

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51
Q

What sort of cells do you expect to see with GIST on histopath?

A

Spindle shaped cells

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52
Q

With GIST, what positive maker would you expect to see?

A

CD117 positive in 50% of cases (C-kit positive)

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53
Q

How is prostate Ca treated?

A

Organ confined - radical prostatectomy comparable to radical radiotherapy

Neo-adjuvant and adjuvant hormones for higher risk tumours treated with radiotherapy

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54
Q

How is prostate Ca treated?

A

Organ confined - radical prostatectomy comparable to radical radiotherapy

Neo-adjuvant and adjuvant hormones for higher risk tumours treated with radiotherapy

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55
Q

In castrate-sensitive metastatic prostate cancer, patients with which symptoms benefit most from anti-androgen cover? Name 3 symptoms.

A

Extensive vertebral metastases

Risk of urinary retention

Poorly controlled pain

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56
Q

What is the treatment for metastatic castrate-resistant prostate cancer?

A

Chemo - docetaxel, cabazetaxel

Novel androgen receptor targeted therapies - abiraterone, enzalutamide

PARP inhibitors

Radiopharmaceuticals - radium-223, lutetium-PSMA

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57
Q

What is the treatment for metastatic castrate-resistant prostate cancer?

A

Chemo - docetaxel, cabazetaxel

Novel androgen receptor targeted therapies - abiraterone, enzalutamide

PARP inhibitors

Radiopharmaceuticals - radium-223, lutetium-PSMA

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58
Q

What are important toxicities with docetaxel? Name 3.

A

Sensory/motor PN

Neutropenic sepsis

Hypersensitivity reactions

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59
Q

What are important toxicities to consider with cabazitaxel? Name 4.

A

Diarrhoea

Cytopenias

Sensory/motor PN (less than docetaxel)

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60
Q

What are important toxicities to consider with abiraterone? Name 4.

A

Hypertension

Hypokalaemia

Peripheral oedema

Transaminitis

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61
Q

What are important toxicities to consider with enzalutamide? Name 3.

A

Hypertension

Fatigue

Contraindicated in seizures

62
Q

What is sipuleucel T, and how is it used?

A

Patient’s own immune cells (APCs) used and combined with prostatic acid phosphates and GM-CSF fusion protein, before being returned to the patient

Used for metastatic castrate-resistant prostate cancer

Side effects are typically immune-based

63
Q

What are the late effects of long term hormonal deprivation for prostate cancer therapy? Name 7.

A

Osteoporosis

Dyslipidaemia

Weight gain

BMD

Mood

Insulin resistance

CVS morbidity / mortality

64
Q

What is the significant side effect of V600E inhibitors such as vemurafenib?

A

Hand-foot syndrome

65
Q

How do the presence of brain mets impact upon melanoma treatment?

A

1-3 mets - stereotactic surgery (SRS) or surgery

> 3 mets - BRAF inhibitors or immunotherapy

66
Q

Name 6 indications for BRCA testing in breast Ca.

A

<40 years old

“Triple negative” pathology <50 years

Bilateral breast Ca, one <50 years

Male breast cancer

Jewish ancestry

Family history of ovarian cancer

67
Q

Name 3 indications for BRCA testing in ovarian Ca.

A

<70 years

Jewish ancestry

Family history of breast or ovarian cancer

68
Q

What should be offered to patients carrying BRCA mutations? Name 3 things for breast Ca, and one for ovarian Ca.

A

Breast

  • offer bilateral mastectomy (best age <40)
  • offer risk-reducing salpingo-oophorectomy (not useful for BRCA1; most are ER/PR -ve)
  • offer screening - annual MRI/MG from age 30 (MG only from 50)

Ovarian

  • RRSO once family complete or <35 (BRCA1), <45 (BRCA2)

No evidence for screening benefit

69
Q

How do PARP inhibitors work?

A

Cell death via synthetic lethality

PARP1 is responsible for base-excision repair. BRCA is responsible for homologous recombination, another mechanism for DNA repair. However, homologous recombination does not occur with a BRCA mutation in place. With both PARP1 and BRCA pathways not intact, no DNA repair occurs, resulting in cell death.

70
Q

What are side effects of PARP inhibitors? Name 4.

A

Nausea

Diarrhoea

Fatigue

Abdominal pain

71
Q

How does sentinel node biopsy help inform treatment plans for breast Ca?

A

Negative sentinel node (70% of patients) - better prognosis overall and no further surgery required

1-2 sentinel nodes involved with cancer - no benefit for axillary dissection noting most get radiotherapy to breast

> 2 sentinel nodes - axillary dissection improves local control

72
Q

What chemotherapy agents are typically used for breast cancer?

A

Anthracycline (doxorubicin, epirubicin) best in meta-analyses

Addition of taxane (paclitaxel, docetaxel) improves on anthracycline alone

2 weekly dose dense chemotherapy better than 3 weekly

Concurrent trastuzumab (Herceptin) in HER2 positive improves disease free survival and survival; standard treatment duration one year

73
Q

How does alcohol impact upon chemotherapy-induced emesis?

A

High ETOH is protective

74
Q

For women with ER +ve breast Ca, how is risk stratified via Oncotype Dx?

A

RS <11 - 1% chance of recurrence at 5 years with endocrine treatment alone

RS 11-25 - no benefit from addition of chemotherapy to endocrine treatment

RS >25 - chemo + hormonal therapy

75
Q

What are side effects of tamoxifen? Name 2.

A

Increased DVT/PE

Increased risk of uterine cancer

76
Q

Describe the interaction between SSRIs and tamoxifen.

A

Blocking of CYP2D6 reduces active tamoxifen metabolites by SSRI - avoid concurrent fluoxetine or paroxetine

77
Q

Name 3 side effects of aromatase inhibitors.

A

Menopausal symptoms

Arthralgia

Accelerated osteoporosis

78
Q

How does fulvestrant work, for whom is it indicated, and what is the major side effect?

A

ER destroyer

For metastatic breast Ca in post-menopausal women

Hepatoxicity

79
Q

What are palbociclib/ribociclib, when can they be used and what is the major side effect?

A

CDK4/6 inhibitor

Metastatic breast Ca in combination with aromatase inhibitor or fulvestrant

Neutropaenia

80
Q

What is everolimus, and when can it be used in breast Ca?

A

mTOR inhibitor

Metastatic breast Ca combined with exemestane

81
Q

Name 3 side effects associated with everolimus

A

Stomatitis

Rash

Fatigue

82
Q

Name 4 different HER2/3 target drugs.

A

Trastuzumab - HER2

Pertuzumab - targets HER2 and HER3 hetero-dimerisation

Lapatinib - oral anti-HER2 agent

T-DM1 - antibody drug conjugate

83
Q

Which tumour markers are associated with seminomas and non-seminomas respectively?

A

Seminomas - bHCG (half-life 5-7 days)

Non-seminomas - AFP (half-life 18-36 hours)

AFP is NEVER seminoma

84
Q

Name 4 risk factors for testicular cancer.

A

Siblings with testicular Ca (6-10x risk)

Crypto-orchidism

Klinefelter’s

Atrophy

85
Q

What is the treatment for stage I (confined to testicle) seminomas following orchidectomy?

A

Option 1 - surveillance

Option 2 - 1 x carboplatin

86
Q

What is the treatment for stage 1 (confined to testicle) non-seminoma?

A

Option 1 - surveillance

Option 2 - 1 x BEP

87
Q

What is the standard chemotherapy regimen for metastatic testicular cancer?

A

BEP (bleomycin, etoposide, cisplatin) for 3-4 cycles

Surgical resection of residual disease in non-seminomas

88
Q

Name 3 side effects associated with cisplatin.

A

Ototoxicity - dose-related, tinnitus; permanent high frequency hearing loss

Nephrotoxicity - average 15% decline in GFR in testicular patients treated with BEP

Neurotoxicity - peripheral (sensory) neuropathy, usually resolves in 6-12 months (may be permanent)

89
Q

What types of chemotherapies are more likely to predispose patients to secondary malignancies?

A

Alkylating agents e.g. cyclophosphamide

90
Q

What material predisposes to the development of mesotheliomas?

A

Blue asbestos (crocidolite)

91
Q

What treatments are available for mesotheliomas?

A

Palliative chemotherapy with cisplatin and pemetrexed

Chemo toxicity can be reduced by concurrent treatment with B12 and folic acid

Some ICI activity in mesothelioma second-line

92
Q

How are NSCLCs treated per stage in general terms?

A

Stage I and II

  • surgery where patient is fit (radical, or SABR if not fit for surgery)
  • adjuvant chemotherapy for resected stage II (hilar nodes involved)

Stage IIIA (ipsilateral mediastinal nodes involved) - radical combination radiotherapy + chemotherapy +/- surgery

Stage IIIB (contralateral mediastinal nodes involved) - palliative chemotherapy and/or radiotherapy

Stage IV (metastatic) - palliative chemotherapy and/or radiotherapy

93
Q

What cancer would cancer cells staining for TTF1 suggest?

A

Adenocarcinoma

94
Q

Name 3 factors that might suggest an EGFR mutation in an adenocarcinoma.

A

Female

Asian

Non-smoker

95
Q

What sort of chemotherapies can be considered for palliative NSCLC?

A

Platinum drug + paclitaxel or gemcitabine or vinorelbine

Adenocarcinomas may do better with pemetrexed combined with platinum

96
Q

In all lung cancers, name 2 factors where PD-L1 expression might be higher.

A

Males

Smokers

97
Q

Name 4 targets for targeted therapies in lung adenocarcinomas.

A

EGFR mutation

ALK translocation

ROS1 re-arrangement

BRAF mutation

98
Q

Name 3 drugs that can be used as targeted therapies in patients with lung adenocarcinoma with an EGFR mutation.

A

Erlotinib

Gefitinib

Afatinib

99
Q

Name 2 drugs that can be used in lung adenocarcinoma with an ALK translocation.

A

Crizotinib

Alectinib

Alectinib has a better response rate (including CNS mets) and disease control at 12 months with lower toxicity than crizotinib

100
Q

Name a drug that can be used in lung adenocarcinoma patients with ROS1 rearrangement.

A

Crizotinib

101
Q

Name a drug combination that can be used in lung adenocarcinoma patients with a BRAF mutation.

A

Trametinib/dabrafenib

102
Q

What are the 6 grades of ECOG?

A

0 - fully active, able to carry on all predispose activities without restriction

1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (e.g. light housework or office work)

2 - Ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours

3 - Capable of only limited self-care; confined to bed or chair more than 50% of waking hours

4 - Completely disabled and not capable of self-care; totally confined to bed or chair

5 - Dead

103
Q

What is sipuleucel T, and how is it used?

A

Patient’s own immune cells (APCs) used and combined with prostatic acid phosphates and GM-CSF fusion protein, before being returned to the patient

Used for metastatic castrate-resistant prostate cancer

Side effects are typically immune-based

104
Q

What are the late effects of long term hormonal deprivation for prostate cancer therapy? Name 7.

A

Osteoporosis

Dyslipidaemia

Weight gain

BMD

Mood

Insulin resistance

CVS morbidity / mortality

105
Q

What is the significant side effect of V600E inhibitors such as vemurafenib?

A

Hand-foot syndrome

106
Q

How do the presence of brain mets impact upon melanoma treatment?

A

1-3 mets - stereotactic surgery (SRS) or surgery

> 3 mets - BRAF inhibitors or immunotherapy

107
Q

Name 6 indications for BRCA testing in breast Ca.

A

<40 years old

“Triple negative” pathology <50 years

Bilateral breast Ca, one <50 years

Male breast cancer

Jewish ancestry

Family history of ovarian cancer

108
Q

Name 3 indications for BRCA testing in ovarian Ca.

A

<70 years

Jewish ancestry

Family history of breast or ovarian cancer

109
Q

What should be offered to patients carrying BRCA mutations? Name 3 things for breast Ca, and one for ovarian Ca.

A

Breast

  • offer bilateral mastectomy (best age <40)
  • offer risk-reducing salpingo-oophorectomy (not useful for BRCA1; most are ER/PR -ve)
  • offer screening - annual MRI/MG from age 30 (MG only from 50)

Ovarian

  • RRSO once family complete or <35 (BRCA1), <45 (BRCA2)

No evidence for screening benefit

110
Q

How do PARP inhibitors work?

A

Cell death via synthetic lethality

PARP1 is responsible for base-excision repair. BRCA is responsible for homologous recombination, another mechanism for DNA repair. However, homologous recombination does not occur with a BRCA mutation in place. With both PARP1 and BRCA pathways not intact, no DNA repair occurs, resulting in cell death.

111
Q

What are side effects of PARP inhibitors? Name 4.

A

Nausea

Diarrhoea

Fatigue

Abdominal pain

112
Q

How does sentinel node biopsy help inform treatment plans for breast Ca?

A

Negative sentinel node (70% of patients) - better prognosis overall and no further surgery required

1-2 sentinel nodes involved with cancer - no benefit for axillary dissection noting most get radiotherapy to breast

> 2 sentinel nodes - axillary dissection improves local control

113
Q

What chemotherapy agents are typically used for breast cancer?

A

Anthracycline (doxorubicin, epirubicin) best in meta-analyses

Addition of taxane (paclitaxel, docetaxel) improves on anthracycline alone

2 weekly dose dense chemotherapy better than 3 weekly

Concurrent trastuzumab (Herceptin) in HER2 positive improves disease free survival and survival; standard treatment duration one year

114
Q

How does alcohol impact upon chemotherapy-induced emesis?

A

High ETOH is protective

115
Q

For women with ER +ve breast Ca, how is risk stratified via Oncotype Dx?

A

RS <11 - 1% chance of recurrence at 5 years with endocrine treatment alone

RS 11-25 - no benefit from addition of chemotherapy to endocrine treatment

RS >25 - chemo + hormonal therapy

116
Q

What are side effects of tamoxifen? Name 2.

A

Increased DVT/PE

Increased risk of uterine cancer

117
Q

Describe the interaction between SSRIs and tamoxifen.

A

Blocking of CYP2D6 reduces active tamoxifen metabolites by SSRI - avoid concurrent fluoxetine or paroxetine

118
Q

Name 3 side effects of aromatase inhibitors.

A

Menopausal symptoms

Arthralgia

Accelerated osteoporosis

119
Q

What is sipuleucel T, and how is it used?

A

Patient’s own immune cells (APCs) used and combined with prostatic acid phosphates and GM-CSF fusion protein, before being returned to the patient

Used for metastatic castrate-resistant prostate cancer

Side effects are typically immune-based

120
Q

What are the late effects of long term hormonal deprivation for prostate cancer therapy? Name 7.

A

Osteoporosis

Dyslipidaemia

Weight gain

BMD

Mood

Insulin resistance

CVS morbidity / mortality

121
Q

What is the significant side effect of V600E inhibitors such as vemurafenib?

A

Hand-foot syndrome

122
Q

How do the presence of brain mets impact upon melanoma treatment?

A

1-3 mets - stereotactic surgery (SRS) or surgery

> 3 mets - BRAF inhibitors or immunotherapy

123
Q

Name 6 indications for BRCA testing in breast Ca.

A

<40 years old

“Triple negative” pathology <50 years

Bilateral breast Ca, one <50 years

Male breast cancer

Jewish ancestry

Family history of ovarian cancer

124
Q

Name 3 indications for BRCA testing in ovarian Ca.

A

<70 years

Jewish ancestry

Family history of breast or ovarian cancer

125
Q

What should be offered to patients carrying BRCA mutations? Name 3 things for breast Ca, and one for ovarian Ca.

A

Breast

  • offer bilateral mastectomy (best age <40)
  • offer risk-reducing salpingo-oophorectomy (not useful for BRCA1; most are ER/PR -ve)
  • offer screening - annual MRI/MG from age 30 (MG only from 50)

Ovarian

  • RRSO once family complete or <35 (BRCA1), <45 (BRCA2)

No evidence for screening benefit

126
Q

How do PARP inhibitors work?

A

Cell death via synthetic lethality

PARP1 is responsible for base-excision repair. BRCA is responsible for homologous recombination, another mechanism for DNA repair. However, homologous recombination does not occur with a BRCA mutation in place. With both PARP1 and BRCA pathways not intact, no DNA repair occurs, resulting in cell death.

127
Q

What are side effects of PARP inhibitors? Name 4.

A

Nausea

Diarrhoea

Fatigue

Abdominal pain

128
Q

How does sentinel node biopsy help inform treatment plans for breast Ca?

A

Negative sentinel node (70% of patients) - better prognosis overall and no further surgery required

1-2 sentinel nodes involved with cancer - no benefit for axillary dissection noting most get radiotherapy to breast

> 2 sentinel nodes - axillary dissection improves local control

129
Q

What chemotherapy agents are typically used for breast cancer?

A

Anthracycline (doxorubicin, epirubicin) best in meta-analyses

Addition of taxane (paclitaxel, docetaxel) improves on anthracycline alone

2 weekly dose dense chemotherapy better than 3 weekly

Concurrent trastuzumab (Herceptin) in HER2 positive improves disease free survival and survival; standard treatment duration one year

130
Q

How does alcohol impact upon chemotherapy-induced emesis?

A

High ETOH is protective

131
Q

For women with ER +ve breast Ca, how is risk stratified via Oncotype Dx?

A

RS <11 - 1% chance of recurrence at 5 years with endocrine treatment alone

RS 11-25 - no benefit from addition of chemotherapy to endocrine treatment

RS >25 - chemo + hormonal therapy

132
Q

What are side effects of tamoxifen? Name 2.

A

Increased DVT/PE

Increased risk of uterine cancer

133
Q

Describe the interaction between SSRIs and tamoxifen.

A

Blocking of CYP2D6 reduces active tamoxifen metabolites by SSRI - avoid concurrent fluoxetine or paroxetine

134
Q

Name 3 side effects of aromatase inhibitors.

A

Menopausal symptoms

Arthralgia

Accelerated osteoporosis

135
Q

What is sipuleucel T, and how is it used?

A

Patient’s own immune cells (APCs) used and combined with prostatic acid phosphates and GM-CSF fusion protein, before being returned to the patient

Used for metastatic castrate-resistant prostate cancer

Side effects are typically immune-based

136
Q

What are the late effects of long term hormonal deprivation for prostate cancer therapy? Name 7.

A

Osteoporosis

Dyslipidaemia

Weight gain

BMD

Mood

Insulin resistance

CVS morbidity / mortality

137
Q

What is the significant side effect of V600E inhibitors such as vemurafenib?

A

Hand-foot syndrome

138
Q

How do the presence of brain mets impact upon melanoma treatment?

A

1-3 mets - stereotactic surgery (SRS) or surgery

> 3 mets - BRAF inhibitors or immunotherapy

139
Q

Name 6 indications for BRCA testing in breast Ca.

A

<40 years old

“Triple negative” pathology <50 years

Bilateral breast Ca, one <50 years

Male breast cancer

Jewish ancestry

Family history of ovarian cancer

140
Q

Name 3 indications for BRCA testing in ovarian Ca.

A

<70 years

Jewish ancestry

Family history of breast or ovarian cancer

141
Q

What should be offered to patients carrying BRCA mutations? Name 3 things for breast Ca, and one for ovarian Ca.

A

Breast

  • offer bilateral mastectomy (best age <40)
  • offer risk-reducing salpingo-oophorectomy (not useful for BRCA1; most are ER/PR -ve)
  • offer screening - annual MRI/MG from age 30 (MG only from 50)

Ovarian

  • RRSO once family complete or <35 (BRCA1), <45 (BRCA2)

No evidence for screening benefit

142
Q

How do PARP inhibitors work?

A

Cell death via synthetic lethality

PARP1 is responsible for base-excision repair. BRCA is responsible for homologous recombination, another mechanism for DNA repair. However, homologous recombination does not occur with a BRCA mutation in place. With both PARP1 and BRCA pathways not intact, no DNA repair occurs, resulting in cell death.

143
Q

What are side effects of PARP inhibitors? Name 4.

A

Nausea

Diarrhoea

Fatigue

Abdominal pain

144
Q

How does sentinel node biopsy help inform treatment plans for breast Ca?

A

Negative sentinel node (70% of patients) - better prognosis overall and no further surgery required

1-2 sentinel nodes involved with cancer - no benefit for axillary dissection noting most get radiotherapy to breast

> 2 sentinel nodes - axillary dissection improves local control

145
Q

What chemotherapy agents are typically used for breast cancer?

A

Anthracycline (doxorubicin, epirubicin) best in meta-analyses

Addition of taxane (paclitaxel, docetaxel) improves on anthracycline alone

2 weekly dose dense chemotherapy better than 3 weekly

Concurrent trastuzumab (Herceptin) in HER2 positive improves disease free survival and survival; standard treatment duration one year

146
Q

How does alcohol impact upon chemotherapy-induced emesis?

A

High ETOH is protective

147
Q

For women with ER +ve breast Ca, how is risk stratified via Oncotype Dx?

A

RS <11 - 1% chance of recurrence at 5 years with endocrine treatment alone

RS 11-25 - no benefit from addition of chemotherapy to endocrine treatment

RS >25 - chemo + hormonal therapy

148
Q

What are side effects of tamoxifen? Name 2.

A

Increased DVT/PE

Increased risk of uterine cancer

149
Q

Describe the interaction between SSRIs and tamoxifen.

A

Blocking of CYP2D6 reduces active tamoxifen metabolites by SSRI - avoid concurrent fluoxetine or paroxetine

150
Q

Name 3 side effects of aromatase inhibitors.

A

Menopausal symptoms

Arthralgia

Accelerated osteoporosis

GCUH FRACP Writtens 2020 (14 decks)

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