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LT22-27

51 important questions on LT22-27

What are exogenous factors of cancer researach in the twentieth century?

environmental
- occupation and environment (social class)
- micro-organisms
- lifestyle

What are endogenous factors of cancer research in the twentieth century?

sex
ethnicity
family disease history
susceptibility to lifestyle factors

Grwoing visibility of cancer due to scientific, instutional, therapeutic, environmental and cultural factors. ligt institutional toe.

19th: special cancer hospitals
20th: journals, international congresses, organisations, specialised research and treatment institutions

Grwoing visibility of cancer due to scientific, instutional, therapeutic, environmental and cultural factors. ligt therapeutic toe.

radiotherapy X rays, radium
nixon's war on cancer: therapeutic optismis, national cancer act, failure

hopes and fears -> history of cancer: changes in treatment and patients experiences

Grwoing visibility of cancer due to scientific, instutional, therapeutic, environmental and cultural factors. ligt environmental toe.

carcinogens; cigarette smoking, radiation, asbetosis, air pollution, personal health
social inequality

resistance economic intersets, political, cultural, professional, difficulties in preventing environmental and lifestyle causes of cancer

Grwoing visibility of cancer due to scientific, instutional, therapeutic, environmental and cultural factors. ligt cultural visibility toe.

disease metaphor
product of modern society

What are the goals of treatment for metastic disesae such as bresat cnancer?

regression of metastases
improvement in symptoms and quality of life
improvement in survival of time
balance toxicity of treatment with relief symptoms due to tumor

we kunnen mensen met metastatic disease niet genezen

What kinds of therapy are there?

endocrine therapy
chemotherapy
targeted therapy

What are the goals of chemotherapy?

Eliminate cancer, shrink the tumor and prolong survival, kill all tumor cells and obtain cure.
Prevent cancer from spreading
Relieve symptoms from cancer, such as pain (palliation

What is known of chemotherapy in metastatic breast cancer?

No cure for metastatic disease.
Sequential signel agent chemotherapy: less toxicity than combination, but mixed chemotherapy has a lower chance of resistance.
Mixed responses due to tumor heterogeneity.

You use combination chemoterahpy in patients with:
- rapid clinical progression
- need for rapid symptom/disease control
- life threathening visceral metastases

What are common chemotherapy toxicities?

Most chemotherapy drugs are active in rapidly dividing cells, so they're also toxic to normal cells.
Common toxicity of chemotherapeutic agents are:
- neutropenia, anemia, thrombocytopenia (bonemarrow suppression -> rode/witte bloedcellen, bloedplaatjes, bloedcel niveaus kunnen naar beneden gaan door chemotherapie)

- mucositis, diarrhea
- nausea and vomiting
- alopecia (haaruitval)
- sterility/infertility

Chemotherapy will be more active in proliferating cells, since they're often in the cell cyle. Aggressive quick dividing cells are a better tumor target with chemotherapy.

How is treatment of breast cancer in an early stage?

Often curable when detected early.
Micrometastsaes can eixst at the time of diagnoses and surgery, leading to eventually reucrrence.
Mutlidisciplinary care is critical for best outcomes: surgery, radition therapy, adjuvant systemic (drug) therapiy reduces risk of recurrence and death.

Patients may develop over the next years still distant metastes.
Adjuvant chemotherapy will reduce this risk and helps cure them. the tumor is less heterogenous

What are side effects of hormonal treatment in prostate cancer?

loss of libido
erectile dysfunction
gynecomastia < a non-cancerous increase in the size of male breast tissue.
osteoporois
hot flashes

How do you get resistant of hormonal treatment in prostate cancer?/

Emergence of androgenj receptor splice variants (ARV7) in the prostate cancer cells.
They protet themselves by making funny androgen receptors. The tumor cells can escape from selective medicines that inhibit the receptor.
You get splice variants that circumvent the given treatment.

What is target therapy?

Drug which inhibits a protin or molecule that is only expressed in cancer or which only the cancer is dependent on.

Offers the promise of reduced side effects compared to less targeted drugs.
Via an important pathway we try to slow down the tumor cells

HER family of receptors als target in borstkanker treatment.

HER2: trastuzumab (herceptin) and pertuzumab (perjeta) bind to distinct epitopes on HER2 extracelular domain.

What is the effect of trastuzumab and chemotherapy on HER2 positive brest cancer?

Improves time to progression and overall survival

Call an example of hormonal therapy in renal cel cancer.

Increased angiogenesis.
VEGFR and VEGF targeted therapy

bevacizumab

What is a biomarker?

measurable indicator of some biological state or condition.
for example, humans shed small parts of cells, proteins, chemicals, DNA and RNA into the bloodstream and environment, as evidence of their presence in a particular location.

They're measured and evaluated to examine normal biological processe, pathogenic processes or pharmacologic responses to treatment.

Blood, urine, other fluids, tissues

What is an ideal marker for diagnosis.

great sensitivity, specificity and accuracy in reflecting total disease burden
prognostic of outcome
predictive of tumor recurrence
predictive of effectiveness of anti-cancer treatments

What are potential clinical application of CTCs?

Blood testing using circulating tumor cells may aid in diagnosis
CTC may serve as a prognostic and predictive biomarker -> changes in CTC counts could indicate sensitivty or resistance to anti-cancer therapy monitoring
The numbers of CTC can be found in the blood as reflectant of the total tumor load in tehe body. If you find thousands of CTCs, patients probably have loads of tumor cells in organs. \

What is the usefulness of biomarker?

Screening
Making a diagnosis
Marker of prognosis -> future outcome of a patient with cancer
Monitoring of treatment efficacy, you want to know whether a toxic chemotherapy works, if it doesn't you want to stop the treatment
detection of recurrence of the disease

When can you use a biomarker for screening?

- highly specific, minimize false positive and negative
- clearly reflect the early stage of the disease
- easily detected without complicated medical procedures
- screening should be cost effective

What is a predictve biomarker?

Marker is predictive when only patients who are marker positive show the treatment effect.
But it is not prognostic, since marker negative patients can do the same as marker positive patients on standard care.

If you have a marker that doesn't decline in effective treatment it is NOT a preditive marker.
So marker is predictive if it is changing only in patients that are responding to the treatment

What is a prognostic biomarker?

If it gives you information independent of any treatment, whether the prognosis/outcome/survival will be favourable or bad.

Marker positive patients do better than marker negative patients on both the treatment arms and the standard of care arms.

But it is not predictive.: even though treated patients do better than all standard of care patients, the magnitude of the difference is the same in both marker positive and negative patients.

For what malignancy is PSA a biomarker?

Prostate cancer
.
When the doubling of PSA is extremly fast, you have a worse prognis. There is an aggressive tumor.

PSA protein is normally made in the prstate gland ind cutal cells that make some of the semen.
Helps to keep the semen liquid

Diagnosis is mostly in serum samples. Detection of PSA allows early detction of prostate cancer.
PSA nearly doubles the rate of detection

PSA is also found in the cytoplasm of benign prostate cancer cells

For what malignancy is CEA a biomarker?

Carcinoembryonic antigen is produced during fetal development.
After birth, the production of CEA stops and is undetectable.
It is elevated in colorectal cancer. >10 ng/ml

Elevation of CEA after cancer treatment correlates with a recurrence of cancer.
CEA has also been found elevated in nonmalignant tumors.

For what malignancy is AFP a biomarker?

Alpha fetoprotein is found in the fetus.
This fetal protein is used as tumor marker in liver cancer and testicular cancer.
Non cancerous liver diseases such as cirrhosis and viral hepatits can lead to high level AFP

liver, >100 ng/ml

For what malignancy is CA19-9 a biomarker?

Present in the fetus in the epithelium of the fetal stomach.
Primarily used as a marker for pancreatic cancer.

For what malignancy is HCG a biomarker?

Human chorionic gonadotropin beta >10 mlU/ml is normally produces by the placenta during pregnancy.
The protein can be detected in serum or urine.
HCG is elevated in majority of testicular cancer patients. Levels of HCG are useful in monitoring the effectiveness of treatment.

malignancies in testis or trophoblast

en AFP.

For what malignancy is CA15-3 a biomarker?

Mamma

For what malignancy is TG/calcitonine a biomarker?

Thyroid

For what malignancy is SCC a biomarker?

cervix

Which stages are there in testicular cancer?

Stage 1: local tumor
Stage 2: periaortic lymph nodes
Stage 3: metastasis to other areas (commonly to lungs)

What treatment for testicular cancer?

Introduction of cisplatinum in the 1970s. cure of young males with metastatic testicular cancer.
Combination chemotherapy including cisplatinum

What is the prognosis of testicular cancer?

Those that have lousy decline of the tumor will have recurrence.
AFP, HCG and LDH useful

Good prognosis, 5 yr 92%
Intermediate prognosis 5 yr 80%
Poor prognosis, 5yr 48%

Intermediate:
1000 <AFP < 10.000
500 < HCG < 50.000
1,5 < LDH < 10 x

What is systemic treatment?

beyond the board of loco-regional in different organ, needs chemotherapy or hormonal therapy, often used in combination with surgery, radiation

What is en-bloc treatment?

Treatment of the breast in combination with lymph nodes, breast and the lymph nodes in one resection specimen.
En-bloc means the whole loco-regional disease in one bloc treated

What is diagnostic therapeutic treatment?

Remove part of the tumor to get a specimen for the pathologist. It is a diagnostic procedure.
Sentinel node is a diagnostic procedure. It is not to treat the patient, but to give the diagnosis

Tell something about the prevalence of breast cancer.

Most prevalent cancer in women.
12.000 new cases per year
Approximately 1 in 10 womne.
5 yrs survival is 85%
Increasing incidence 1% a year

Age of diagnosis:
- 70% over 50 years of age
- 9% under 40 years of age

Factors of influence: nutrition, childbirth, alcohol, physical activity, menstrual cycles: late menarche, arly menopause, childbirth are advantages, most menstrual cycles the highest chance of getting breast cancer.

What role do familial/genetics play in breast cancer?

Familial:
Highest risk RR 6-8
Rare, of all the breast cancers only 5% is associated with genes
Two or moer firt line relative (mother, sister, daughter)
Young age (typically < 40)

Hereditary:
- BRCA1 and 2
- 60-80% life-time risk
- 2% cumulative yearly risk (30-50 yr)
- 1% cumulative yearly risk (50-80 yr)
- 20-40% risk ovarian cancer
In women preventive surgery, after 35-40 remove ovaries.
Since you reduce the risk of brest cancer in bRCA1 and 2 with 50%

If you have a hereditary form of breast cancer, what can be done?

Screening (from age of 25: MRI, from age of 30: MRI + mammogram yearly)
Profylactic surgery, chance of getting breast cancer is still 2-5%
Ovariectomy: BRCA1/2 is also ovarian cancer, if you remove the ovaries, you reduce the risk of breast cancer with 50%

Vertel iets over het bevolkingsonderzoek borstkanker (BOB).

All women 50-75 years
Once every two years

Not at earlier age, because the sensitivity is lower in younger breasts.
Stop at 75, because when age increases, chance of dying from breast cancer diminishes, since you die of other reason like cardiovascular, dementia. Preventing them dying from breast cancer is less important.

What are the goals of breast cancer staging?

Treatment planning (multidisciplinary)
Stratification (comparison between hospital/countries) to detect differences in care and outcome.

When do you use systemic treatment?

if the chance of getting metastasis is high.
It is not used to treat cancer, but because you want to lower the chance of metastases.

almost everywomen with breast cancer gets this chemotherapy, but only a minority of the women will be cured because of the adjuvant chemotherapy

Timeline of treatments: 1890

Halsted
Centrifugal theory of cancer -> cancer starts in the breast and spreads in circles beyond its borders. So only surgery of the tumor is not effective. How larger the surgery, how higher the chance of curing the patients.

RADICAL MASTECTOMY
- removal of the pectoral muscle
- removal of the breast
- removal of the lymph nodes in the axilla or around the collar bone

Lots of patients died.

Timeline of treatments: 1974

Fisher
RCT van radiotherapy, minder local-regional surgery
- drie armen RCT
- 25 jaar follow up

Cure rate was around the same. So less surgery with using radiotherapy will give you the same local control.
A protocol to compare segmental mastectomy and axillary dissection with and without metastasis. Maybe spare the breast.

Timeline of treatments: 2011

Giluliano
Z0011 trial, women with axillary dissection might have a poor quality of life.
We shouldn't do clearance of all lymph nodes, but only the most prognostic one = sentinel node.
Maybe only radiotherapy int he axilla.

What is the sentinel node?

Tumour with injected labelling substance.
Sentinel lymph node with abosrbed labelling substance

It is the first node the fluid is detected. If the sentinel node is clean, there cannot be cells beyond that.
So sentinal node is used for diagnostic procedure.
If the sentinel node is clean, maybe no axillary dissection.

What is trend of treating breast cancer over the yeras?

Radical mastectomy
Modified mastectomy
Radiotherapy
So surgery over the years diminishes.

Neo-adjuvant treatment increases.
HER2 positive breast cancer, neoadjuvant treatment gives you a complete response rae. More than half of the tumor cells will be gone.

How to treat a small tumor, low grade, no lymph node involvement.

nowadays, we give radiotherapy.
If you irradiate all patients after surgery, you have 1.2% local regional recurrence rate.
If we don'nt irradiate any of them, you only get 2% higher local regional reurrence rate.
So we're actually overtreating!

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MOD2

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