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Thema 3: Neoplasma/nieuwvorming I. Een complete samenvatting van alle tentamenstof! €4,99   In winkelwagen

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Thema 3: Neoplasma/nieuwvorming I. Een complete samenvatting van alle tentamenstof!

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  • 18 augustus 2022
  • 56
  • 2021/2022
  • Samenvatting
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KatieZara
Theme 3:


Neoplasms I
Summary




1

,Content
Week 9: General principles of oncology and breast cancer....................................................................5
Oncological language..........................................................................................................................5
Curative..........................................................................................................................................5
Palliative.........................................................................................................................................5
Scoring the patient’s physical condition.........................................................................................5
Primary therapy..............................................................................................................................6
Adjuvant therapy............................................................................................................................6
Neoadjuvant therapy......................................................................................................................6
The hallmarks of cancer......................................................................................................................7
The normal cell cycle......................................................................................................................7
Self-sufficiency of growth...............................................................................................................7
Insensitivity to growth inhibition....................................................................................................8
Evasion of apoptosis.......................................................................................................................8
Unlimited replication......................................................................................................................8
Angiogenesis...................................................................................................................................8
Invasion and metastasis..................................................................................................................8
Deregulating cellular energetics.....................................................................................................9
Genomic instability.........................................................................................................................9
Avoiding immune destruction/tumour enabling inflammation......................................................9
Inflammation can stimulate tumour growth:.................................................................................9
Breast caner......................................................................................................................................10
Cancer diagnostics............................................................................................................................11
Clinical signs..................................................................................................................................11
Symptoms and diagnostics of breast cancer.....................................................................................12
Basic diagnostics...........................................................................................................................12
Symptoms of early breast cancer.................................................................................................12
Symptoms of advanced breast cancer..........................................................................................13
History taking................................................................................................................................14
Mammography.............................................................................................................................14
Ultrasound....................................................................................................................................15
MRI...............................................................................................................................................15
Chest X-ray vs CT scan..................................................................................................................16
Fine needle aspiration..................................................................................................................16
Core needle biopsy.......................................................................................................................17


2

, FDG-PET/CT..................................................................................................................................17
Breast cancer imaging: CT thorax/abdomen.................................................................................17
TNM and cancer staging...................................................................................................................19
TNM..............................................................................................................................................19
UICC staging..................................................................................................................................20
Cancer treatment.............................................................................................................................21
Surgery.........................................................................................................................................21
Radiotherapy................................................................................................................................21
Systemic therapy..........................................................................................................................22
Chemotherapy..............................................................................................................................23
Immunotherapy............................................................................................................................24
Hormonal therapy........................................................................................................................24
PARP inhibitors:............................................................................................................................24
Follow-up and aftercare...................................................................................................................24
Palliative treatment and care...........................................................................................................27
Statistics...........................................................................................................................................28
Risk...................................................................................................................................................29
Case 1:..........................................................................................................................................29
Case 2:..........................................................................................................................................30
Bayesian thinking..........................................................................................................................30
Week 10: Fever, bleeding and fatigue..................................................................................................31
Haematopoiesis................................................................................................................................31
Leukaemia........................................................................................................................................32
Acute leukaemia...........................................................................................................................32
Common symptoms and their causes...........................................................................................33
Chronic leukaemia........................................................................................................................34
Treatment of leukaemia...................................................................................................................35
Acute leukaemia...........................................................................................................................35
Treatment choice..........................................................................................................................36
Treatment of chronic leukaemia...................................................................................................37
Immunotherapy................................................................................................................................38
New developments.......................................................................................................................39
Week 11: Itch, fever and swollen glands..............................................................................................41
Lymphadenopathy............................................................................................................................41
The lymph nodes and B-cell formation.............................................................................................41
The structure of an antibody........................................................................................................41

3

, Selection.......................................................................................................................................42
Activation of B-cells......................................................................................................................43
B-cell lymphomas.............................................................................................................................46
Classification:................................................................................................................................46
Staging of lymphoma....................................................................................................................48
IPI score........................................................................................................................................48
Follicular lymphoma.....................................................................................................................52
Diffuse large B-cell lymphoma......................................................................................................52
Diagnosis of lymphoma................................................................................................................53
R-CHOP treatment........................................................................................................................54
Post-treatment.................................................................................................................................55
Chemotherapy..............................................................................................................................55
Radiotherapy................................................................................................................................56
Secondary malignancies...............................................................................................................56




4

,Week 9: General principles of oncology and breast
cancer
Oncological language
Curative
- Free of cancer until death because of other cause
- No detectable disease after treatment
Treatment without curative intent = aim to render the patient disease-free
Curative treatment does not mean being cured!
 Breast cancer 10-year survival is 90%
 Pancreatic cancer survival is 15-25% 5-year survival
Palliative
 When the disease cannot be cured  treatment that alleviates the symptoms of a
disease (less toxicity)
o Radiotherapy for painful bone metastasis
o Oral chemotherapy to decrease liver metastasis to diminish fatigue
o Mastectomy for an ulcerative breast cancer patient with a few bone
metastasis
The surprise question: Would I be surprised if this patient died in the next year?
 Survival prognosis
Some cancers become more of a chronic disease
Scoring the patient’s physical condition
Karnofsky score from 100%-0%
 70% = caring for self, not being able to do normal activities or work
 30% = severely disabled, hospital admission required but death is not inevitable
ECOG score

ECO Description
G
0 Fully active, able to carry on all pre-disease performance without restriction
1 Restricted in physically strenuous activity, but ambulatory and able to carry out
work of a light sedentary nature (e.g. light house work or office work)
2 Ambulatory and capable of selfcare, but unable to carry out any work activities (up
and about more than 50% of waking hours)
3 Capable of only limited selfcare, confined to bed or chair more than 50% of waking
hours  makes it difficult to give chemotherapy because that would up the score
to 4
4 Completely disabled. Cannot carry on selfcare. Totally confined to bed or chair

5

, 5 Dead


Primary therapy
 Taking the tumour away with a curative intent
Surgery has the largest impact on survival:
- Breast cancer
- Colon cancer
- Melanoma
- Sarcoma
Sometimes radiotherapy is first-line therapy:
- Early squamous cell carcinoma of the larynx
- Some lung cancers
- Early prostate cancer
Sometimes chemotherapy in non-solid cancers: leukaemia
Local treatment = applied to the tumour site
Systemic treatment = applied to the entire body
- Chemotherapy
- Immunotherapy
- Antihormonal therapy
Adjuvant therapy
= in addition to primary therapy  to prevent recurrence
- Radiotherapy after conservative breast surgery
- Radiotherapy after colon resection
Neoadjuvant therapy
= before surgery to decrease the size of the tumour and make the surgery less aggressive
 Also to make the chemotherapy schedule more personalised




6

,The hallmarks of cancer
The normal cell cycle




G1 (gap) phase: growth to a normal size after mitosis
 Restriction point: repression of entering a new cell cycle  can only be passed if
circumstances are beneficial (e.g. enough nutrients or undamaged DNA or when
growth factors are present)
G0 phase: the cell differentiates to carry out certain functions  no longer divides
 Some cells can enter the cell cycle again after positive stimuli
S (synthetic) phase: DNA replication and linking of the sister chromatids
 G1/S checkpoint: check for DNA damage or stalled replication forks by p53
G2 (gap) phase: key enzymes for mitosis are converted into their active forms
 G2/M checkpoint: check for damaged or unduplicated DNA
M (mitosis) phase: mitosis of the cell
Most cells are in the interphase (G1 t/m S)
Self-sufficiency of growth
Normal growth: growth factor binds to receptor  after stimulus is removed, growth it
stopped
 Cancer cells can make their own growth stimuli due to mutations in oncogenes:
o Production of growth factors (e.g. cyclins) = autocrine stimulation
o Production of growth receptors

7

, o Mutation in downstream pathways

Insensitivity to growth inhibition
Normally: APC inhibits β-catanin  when growth signal comes APC is broken down  β-
catanin signals the cell to grow
 In cancer cells APC is not present due to a mutation in the gene coding for it
In general: mutations in tumour suppression genes (like APC) lead to insensitivity to growth
inhibition
Evasion of apoptosis
Normally: cells with DNA damage are detected by p53 (at the G1/S checkpoint)  repair or
apoptosis
 Tumour cells often have a mutation in p53  no DNA repair or apoptosis
Unlimited replication
Normally: number of times a cell can divide is limited  after 40-50 replication cycles, the
telomeres are gone  the cell will be forced into the resting phase by p53
 In tumour cells:
o P53 is often defect  cell division continuous (with DNA damage)
o Activation of telomerase  telomeres are lengthened  infinite growth

Angiogenesis
Cells have to lie within 2 mm from the closest blood vessel  otherwise hypoxia and not
enough nutrients  necrosis
 Tumour cells produce angiogenic factors  production of a vasculature to supply
the tumour
Invasion and metastasis
Cancer cells show abnormal morphological features called dysplasia
- Slightly abnormal = low-grade dysplasia
- Moderately abnormal = middle-grade dysplasia
- Highly abnormal = high-grade dysplasia or carcinoma in situ  the beginning of
cancer
The basal membrane separates the epithelial layer from the stromal compartment (contains
blood and lymph vessels)
 Dysplastic cells have not (yet) invaded the stroma  if they do, the tumour can
metastasise
When the tumour invades the epithelial cell layer  they can invade the stroma and
metastasise = invasion




8

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