a) PRINCIPLES OF ONCOLOGY Flashcards

Question 1

Q

Primary and secondary prevention, screening in oncology.
Definition

Answer

A

Prevention strategies focus on modifying environmental and lifestyle risk factors related to cancer.
Primary prevention: Stopping the disease from occurring by removing risk factors.
Eg. Vaccination, no smoking regulations, ovariectomies and mastectomies…

Secondary prevention: Early detection of a disease, when it has already happened, in order to reduce its progression. Screening and early treatment.

We also have tertiary prevention, which includes treatment measures to reduce the effects and complications of a disease, and quaternary prevention, which are methods to mitigate or avoid the consequences of unnecessary interventions in the healthcare system.

Question 2

Q

Primary and secondary prevention, screening in oncology.
Theory of successful screening

What is screening Properties of a good screening test Measure of success

Answer

A

Screening is part of secondary prevention procedures, performed on part of the asymptomatic population, at risk of a disease. It does not diagnose the disease, however it helps determine which subjets we should further test.

Screening can be opportunistic, when offered to patients consulting their doctor for another reason, or population based, as part of a campaign, covering a predefined age range.

Screening tests should be:
- Cheap
- Available for everyone
- Easy to perform
- Highly sensible and specific
- Safe

THE BEST MEASURE OF SUCCESS IN SCREENING IS A DEMOSTRABLE REDUCTION IN MORTALITY IN THE SCREENED POPULATION

Question 3

Q

Primary and secondary prevention, screening in oncology.
Screening in the clinical practice

Examples of screening tests for cancers

Answer

A

COLORRECTAL CANCER
CERVICAL CANCER
BREAST CANCER
LUNG CANCER
PROSTATE CANCER

Question 4

Q

Primary and secondary prevention, screening in oncology.
Screening in the clinical practice

COLORRECTAL CANCER

Answer

A

Stool based tests: Fecal occult blood test and fecal immunochemical test
Endoscopic techniques: Colonoscopy, CT colonography or flexible sigmoidoscopy

Start screening at the age of 45-50:
* 50-54 y: Fecal occult or inmunochemical test every year, if POSITIVE: colonoscopy
* > 55y: Fecal occult or inmunochemical every year OR colonoscopy every 10 years

For high risk patients, screening should be performed earlier depending on condition.

Question 5

Q

Primary and secondary prevention, screening in oncology.
Screening in the clinical practice

CERVICAL CANCER

Answer

A

Papanicolau test: A cytology from de cervical and vaginal cells, performed to detect abnormal cells.
HPV testing: Looks for high-risk HPV types in cervical cells. Ex. 16, 18.

Pap smears are recommended once a year, from the onset of sexual activity.

Question 6

Q

Primary and secondary prevention, screening in oncology.
Screening in the clinical practice

BREAST CANCER

Answer

A

Bilateral mammography recommended from 45 onwards. Annual until 55, and decreasing to every two years from then.

Question 7

Q

Primary and secondary prevention, screening in oncology.
Screening in the clinical practice

LUNG CANCER

Answer

A

Low dose chest CT performed on high risk individuals.

Question 8

Q

Primary and secondary prevention, screening in oncology.
Screening in the clinical practice

PROSTATE CANCER

Answer

A

Only two countries actually screen for prostate cancer: Lithuania and Kazakhstan.

Techniques include digital rectal examination and PSA quantification (PSA > 4.0 ng/mL).

Question 9

Q

Tumor epidemiology
Descriptive and analytical epidemiology

Answer

A

Epidemiological studies focus on statistical studies of human diseases in the population.
* Descriptive studies describe disease distribution in a certain population, exposing the facts (incidence, mortality, prevalence rates, or trends)
* Analytical studies focus on the relationship between disease and exposure, establishing risk factors.

Question 10

Q

Tumor epidemiology
Regional differences in cancer incidence and mortality

Incidence, mortality and prevalence definitions

Answer

A

Incidence: Nº of newly detected cases in a certain period of time and population.
Mortality rate: Nº of cancer patients that died during a period of study.
Prevalence: Nº of living patients with cancer.

Question 11

Q

Tumor epidemiology
Regional differences in cancer incidence and mortality

Most frequent cancers worldwide, in both sexes. Incid and mort

Answer

A

Incidence:
1. Breast
2. Prostate
3. Lung
4. Colorrectal

Mortality:
1. Lungs
2. Breast
3. Prostate / colorrectal / stomach / liver

The highest incidence and mortality in the world is in Australia

Question 12

Q

Tumor epidemiology
Regional differences in cancer incidence and mortality

Most frequent cancers in men. Incidence and mortality

Answer

A

Incidence:
1. Prostate
2. Lung
3. Colorrectal

Mortality:
1. Lung
2. Prostate
3. Colorrectal

In developing countries, the most common cancer in men is liver cancer because of the great incidence of HBV and HCV.

Question 13

Q

Tumor epidemiology
Regional differences in cancer incidence and mortality

Most frequent cancers in women. Incidence and mortality

Answer

A

Incidence:
1. Breast
2. Lung
3. Colorrectal
4. Cervical

Mortality:
1. Lung
2. Breast
3. Colorrectal

Question 14

Q

Tumor epidemiology
Regional differences in cancer incidence and mortality

What explains them?

Answer

A

Worlwide incidence and mortality rates may not be the same when we look at certain countries or populations. Eg. Most common cancer in men from developing countries is liver cancer, not prostate, due to incidence of HBV and HCV.

Differences in cancer incidence and mortality can be explained by changes in screenings, awarness and risk factors.

Question 15

Q

Tumor epidemiology
Hereditary cancer syndromes

Answer

A

They make up 10-15% of cases, leading specially to early onset cases

Examples include:
* Breast cancer - related to BRCA1/2 mutations or TP53
* Colorrectal cancer: Lynch syndrome
* Prostate cancer - related to BRCA1/2 gene mutations
* Renal cancer: Von Hippel Lyndau sd
* Others

Question 16

Q

Biology of cancer growth
Carcinogenesis

Definition and steps

Answer

A

A multistep process by which normal cells turn to neoplastic cells, and eventually into a tumor. The process starts with a genetic mutation, which will accumulate and finally transform the phenotype.

Alterations may directly turn into specific genes that control proliferation of cells, apoptosis or differentiation, or affect gene expression (epigenetic changes).

Cancer incidence increases with age as the probability of neoplatic transformation increases with cell divisions.

STEPS:
1. Initiation: A mutation occurs due to carcinogen exposure, on tumor suppressing genes or protoncogenes.
2. Promotion: Said mutation survives and slowly expands as cells replicate.
3. Latent period: The mutated cells have replicated enough to survive, but are being limited by our own defences, such as tumor suppressing genes, or by lack of access to host’s blood supply.
4. Tumorigenesis or progression: Exclusive to malignant transformation. It implies the ability of the tumor to invade neighboring tissue, and even those at a greater distance, through angiogenetic processes. The malignant cells are able to overcome whatever defences were stopping them during the latent period, in order to grow further.

Question 17

Q

Biology of cancer growth
Physical carcinogens (radiation)

Non ionizing and ionizing radiation

Answer

A

Non ionizing radiation: UV radiation
Comes mainly from sunrays and affects mostly ligh skinned individuals. It is related to skin squamous cell carcinoma, basal cell carcinoma and skin melanoma.
UV-C is directly absorbed by the ozone layer, UV-B forms pyrimidine dimers that damage DNA (in moderation, they can be repaired into the correct DNA by cell repair mechanisms, but with severe and prolonged exposure these are overwhelmed and they cannot repair enough), UV-A can contribute indirectly in carcinogenesis through ROS formation.

Ionizing radiation:
Can cause DNA damage directly or indirectly:
* Direct damage: Radiation interacts directly with the atoms of DNA or other components of the cell.
* Indirect damage: More common. Radiation interacts with water molecules and forms free radicals (ROS) which will further interact with cellular components.

Question 18

Q

Biology of cancer growth
Chemical carcinogenesis

Steps and types of carcinogens, promoters

Answer

A

Chemical carcinogens must be highly reactive electrophiles that react with nucleophilic sites in the cell, like DNA, RNA and proteins.

Steps:
1. Initiation: Exposure to chemicals causes DNA damage, which can lead to DNA repair, cell death or permanent damage.
2. Promotion: Mutated cells pass DNA damage to daughter cells, resulting in clonal expansion of the cells into a malignant neoplasm.
3. Progression: Proliferated cells form a mass where cells accumulate genetic abnormalities that eventually form a heterogeneus cell population.

Types:
* Direct carcinogens: They dont require any metabolic activation to become active. Eg: Alkylating agents, acetylating agents
* Indirect carcinogens: They need metabolic transformation to become active. Activation usually requires cytochrome p450 dependen mono-oxygenase or could also be through combustion. Eg: Benzopyrene formed in the combustion of tobacco.

Promoters increase the carcinogenic effect of a carcinogen, although they aren’t carcinogenic on their own. An example is BPA.

Question 19

Q

Biology of cancer growth
Viral carcinogenesis

Answer

A

They act through insertational mutagenesis, viral oncognes, inmunosupression or apoptosis stop.

DNA viruses: They insert the genome into DNA and carry out a lytic cycle.
* HPV (16, 18, 31 or 33), related to cervical, vaginal, or vulvar carcinomas; the virus encodes for E6 and E7 protins that have carcinogenic effect.
* EBV related to Burkitt’s lymphoma and nasopharyngeal carcinoma. It interacts with B cells without killing them, remaining latent and producing viral proteins in the cells.
* HBV related to chronic liver inflammation, which leads to hepatocellular carcinoma
* HHV8 related to Kaposi sarcoma

RNA viruses:
* HCV related to chronic liver inflammation, which leads to hepatocellular carcinoma
* HTLV-1 is the main cause of adult T cell leukemia/lymphoma.

There can also be bacterial carcinogens such as Helicobacter pylori which is related to gastric adenocarcinomas and gastric MALT lymphomas

Question 20

Q

Molecular biology in oncology
Oncogenes

Answer

A

Mutated protoncogenes, promotors of celullar proliferation that when mutated, promote unregulated celullar growth, leading to tumor formation.

Only one oncogene is needed to initiate malignant transformation.

Examples: RAS, c-myc

Question 21

Q

Molecular biology in oncology
Tumor supressing genes

Answer

A

Genes that normally stop uncontrolled growth from occurring. There are two main kinds:

Gate keepers: Directly downregulate cell growth. Eg. p53, Rb, APC…
Care takers: Protect genome integrity, so if mutated, it leads to an accumulation of mutations. Eg. BRCA or MSH

Two mutations are needed to initiate the process.

Question 22

Q

Molecular biology in oncology
Gene therapy

Answer

A

A rapidly evolving field based on the introduction of an exogenous gene(s) into a patient’s cells to either replace or disrupt defective genes, as a method to treat a disease.

In oncology, gene therapy may be used in:
* Antitumor inmune response: Increases a patient’s inmune response against tumor cells.
* Direct tumor lysis: Introducing a genetically engineered virus that targets and destroys cancer cells via expression of cytotoxic proteins that lead to cancer cell lysis
* Gene transfer: New treatment in which we introduce a foreign gene into de cancerous cell’s DNA through CRISPR, that leads to the cell’s destruction (suicide genes, marker genes, antiangiogenesis genes…)

Question 23

Q

Medical history and physical examination in oncology
Medical history aspects

Answer

A

Present complains: Tumor dx, current tx, reason for admission
Family history: Cancers in the family, age, gender
Personal history: Comorbidities, medication, previous cancers or diseases
Gynaecological history: Age of menarche/menopause, regularity of the cycle, nº of pregnancies, births, abortions, breastfeeding…
Allergies
Toxic habits: Smoking, drug abuse, alcohol
Current illness

Question 24

Q

Medical history and physical examination in oncology
Specific clinical signs/symtoms

Answer

A

Horner’s syndrome: Ptosis, miosis, anhydrosis due to a disruption in the sympathetic nerve supply
Virchow’s node: Left supraclavicular lymph node. Often related to malignant gastric cancer.
Sister Mary Joseph’s node: Subcutaneus lymph node found in the umbilicus region, often related to ovarian cancer
Fluid accumulation in serosal cavities
Changing nevus or new hyperpigmented cutaneous lesions related to melanoma
Painless jaundice often related to malignant biliary obstruction

Question 25

Q

Medical history and physical examination in oncology
Non specific cancer signs/symptoms

Answer

A

Anorexia
Unexplained weight loss
Unexplained pain
Lumps in breast, testicles, swollen lymph nodes…
Bleeding (bowel, bladder, vagina, lung…)
Odynophagia
Skin rash or pigmentation
Seizures

Question 26

Q

Medical history and physical examination in oncology
Physical examination

Answer

A

Inspection
Palpation: tonus, temperature, moisture of the skin
Percussion: Resonance (healthy lungs), hyper-resonance (over expanded lungs or pneumothorax), tympanic (normal over airfilled abdominal organs but pathological in lung bullae or pneumothorax), flat (dense airless organs), dull (between resonant and flat, indicating exudate or effusion).
Auscultation

Question 27

Q

Medical history and physical examination in oncology
Clinical manifestations of cancer

Answer

A

Pain: From pressure, obstruction, invasion, tissue invasion or inflammation
FATIGUE
Cachexia: Loss of appetite, early satiety, weakness, taste changes
Anemia: Malnutrition, chronic bleeding
**Leukopenia **: From chemo or RT
Infection: From leukopenia, inmunosuppression… Main cause of complications and death.

Question 28

Q

Medical history and physical examination in oncology
Paraneoplastic syndrome

Answer

A

Appear in almost 10-15% of cancers, as a result of the spread of substances released from the tumor or via the inmune response to it.

Examples: SIADH, Cushing’s sd, anemia, polycythemia, tumor induced osteomalacia…

Question 29

Q

Question 30

Q

Medical history and physical examination in oncology
Hereditary cancer syndromes

Answer

A

These often are early onset. They include:
* Li Fraumeni syndrome: A germline mutation in TP53 gene related to breast cancer, sarcomas, brain tumors and adrenocortical carcinomas.
* Lynch syndrome: Autosomic dominant disease related to colon, endometrial, ovarian, stomach cancers.
* BRCA1/2 mutations: Often related to hereditary breast and ovarian cancers, as well as prostate, pancreatic, colon and melanoma.

Question 31

Q

Diagnostic imaging in oncology
Uses of xray, CT, US, MRI

Answer

A

Screening: Mammography for breast cancer, CT for lung cancer
Detection and diagnosis: Characterization, anatomical localization… The appearance of primary tumors may be characteristic, but only cytology and histology will give a definitive diagnosis.
Staging (TNM)
Monitoring treatment
Interventional procedures: Biopsies, insertion of stents, embolization of vascular tumors, laser surgery…
Radiotherapy planning: Essential in defining: GTV (Gross tumor volume), CTV (Clinical target volume), PTV (Planning target volume), OAR (Organs at risk).

Question 32

Q

Nuclear medicine in oncology
Uses

Answer

A

Staging
Searching for cancer of unknown primary site
Evaluation of therapeutic effect
Demonstration of residual tumor mass
Restaging
Examination before radionuclide therapy

Question 33

Q

Nuclear medicine in oncology
Radionucleotide scintigraphy

Answer

A

Based on administering a radio-labelled agent that emits gamma-rays, which will be detected through gamma cameras to produce a 2D image that shows the isotope’s distribution through the body.

Isotopes can be organ specific or receptor specific, rather than tumor specific. The most commonly used is Tc99.

This works best for bone metastasis and thyroid.

Question 34

Q

Nuclear medicine in oncology
SPECT

Answer

A

Single photon emission tomography

Obtains multiple 2D images from different angles, in order to reconstruct them into a 3D image. It doesn’t show a body part’s anatomical structure, rather it shows the function of an organ or metabolic activity. This is similar to PET scans; the main difference between both is that SPECT scans use gamma rays (Tc99) to create the image.

The image shows increased organic activity or metabolism, which may mean there’s a tumor (which have a high metabolic activity), but it doesn’t necessarily have to; it could also mean there’s an inflammatory process going on, for example.

Question 35

Q

Nuclear medicine in oncology
PET scan

Answer

A

Positron Emission Tomography

This is the most sensitive functional imaging technique. It’s nº1 for staging, although it is quite expensive.

It’s based on the administration of positron emitters and detection of pairs of annhiliation positrons; annhiliation occurs in 180º to either side, creating lines that are recorded (coincidence detection) an used for tomographic reconstruction.

We are administering positron emitters, but detecting gamma photons.

90% of PET scan use is for oncology.

Question 36

Q

Nuclear medicine in oncology
Scentinel lymph node mapping

Answer

A

A radioisotope is injected into the primary tumor, which we track, allowing us to find the first draining node of said tumor; this is the scentinel node, which will be removed for histopathology.

Thanks to this technique, we avoid removing the entire nodal group, which can have many more side effects.

This technique is mainly used in breast cancer, melanoma and is in trials for thyroid cancer.

Question 37

Q

Tumor verification
Histopathology, cytology and biopsy

INTRO

Answer

A

Histopathological verification is the phase that confirms the diagnosis of cancer. The only way of confirming a definitive diagnosis is by taking a sample tissue to verify under a microscope.

Without verification, we have no diagnosis and so we cannot treat.

There are some exceptions to the rule, for example hepatocellular carcinoma and some pancreatic cancers in specific situations.

Question 38

Q

Tumor verification
Histopathology, cytology and biopsy

Histopathology is important for

Answer

A

Making an accurate diagnosis (primary tumor vs. mets)
Staging and grading (TNM)
Deciding the aim of treatment (palliative vs. curative)
Choosing treatment methods (eg. targeted therapy)

Question 39

Q

Tumor verification
Biopsy vs. Cytology

Answer

A

Cytology: Observation of single cells collected from a suspicious area. Eg. Pap smear, BAL… Techniques include exfoliative cytology (grabbing cells from the surface or body cavity) and fine-needle aspiration.

Biopsy: Obtains enough tissue for histologic examination. It’s more accurate than cytology but harder to obtain and more prone to complications.
Techinques: core needle biopsy, incisional biopsy, excisional bipsy, scentinel lymph node biopsy…

Question 40

Q

Tumor verification
Benign tumor characteristics

Answer

A

Often smaller and with well demarcated borders
Slow growth rate
Well differentiated
No local invasion
No metastasis

Question 41

Q

Tumor verification
Malignant tumors characteristics

Answer

A

Often larger, with necrosis and hemorrage around them
Poorly demarcated
Pleomorphism (cells vary in shape and size) and disorganized growth
Abnormal nuclear morpholgy
High mitotic activity
Rapid growth rate
Differentiation rate varies
Local invasion
Metastatic potential

Question 42

Q

Tumor verification
Grading

Answer

A

Low grade and high grade tumors
* Low grade tumors: Well differentiated
* High grade tumors: Poorly differentiated

Broder’s grading
* Grade I: Well differentiated (<25% anaplastic cells)
* Grade II: Moderately differentiated (25-50% anaplastic cells)
* Grade III: Poorly differentiated (50-75% anaplastic cells)
* Grade IV: Anaplastic (>75% anaplastic cells)

Grading is important in determining the prognosis, as well differentiated tumors have a better prognosis. Although some well differentiated tumors can be very aggressive.

Question 43

Q

Haematological and biochemical analysis in oncology
Whole blood count

Answer

A

Most blood cancers can be detected by a complete blood count, but also other cancers can cause blood count alterations.

Normal ranges:
* WBC: 4500-11000 /mm3
* Hb: 3.5-5.9 million/mm3 (m&w)
* Hc: 36%-53% (m&w)
* Platelets: 150,000-400,000/mm3

Anemia of chronic disease is common in cancer patients. Policitemia vera can occur due to elevated EPO production in renal cell carcinoma, coagulation deffects can happen when the liver is affected (cancer or mets)…

Question 44

Q

Haematological and biochemical analysis in oncology
Biochemistry

Answer

A

It is important to watch out for alterations of:
* Creatinine
* Urea
* Uric acid
* Na+, K+, Cl-, Ca2+
* Total proteins
* Bilirrubin
* ALT & AST
* GMT & ALP
* PSA

Question 45

Q

Haematological and biochemical analysis in oncology
Serum oncomarkers

Answer

A

Substances found in the blood, associated to certain tumors, which are useful in monitoring the tumor’s response to treatment and detecting relapses. With the exception on PSA for prostate cancer, oncomarkers are not used for screening.

Ex. CEA, AFP, Calcitonin, CA15-3, CA19-9…

Question 46

Q

Staging
Principles of staging

Definition of staging

Answer

A

It is the determination of the amount or spread of cancer in the body through physical examination, imaging techniques, lab tests and biopsies, so that we can plan the appropriate treatment and estimate the prognosis of the disease.

Question 47

Q

Staging
Types of TNM staging

Answer

A

T (extent of the tumor), N (regional lymph node involvement), M (presence of metastasis)

cTNM: Clinical TNM. Based on patient history, physical examination, and any imaging done before treatment begins. CT and MRI are mostly used.

pTNM: Pathological TNM, based on clinical stage and information added or modified by operative findings and pathological evaluation of the resected specimens.

ypTNM: Stage determined after treatment.

TNM does not apply to brain cancers, as they don’t metastasize, or to lymphomas, as they start on lymph nodes themselves.

Question 48

Q

Staging
Example of TNM staging for colorrectal cancer

Answer

A

Primary tumor
* TX: not accessible
* T0: no signs of primary tumor
* Tis: Carcinoma in situ (intraepitelial or lamina propia invasion)
* T1: Submucosal invasion
* T2: Tunica muscularis propia invasion
* T3: Tumor growth over muscularis propia to subserose o perirectal tissue
* T4: Tumor grows to other organs

Regional lymph nodes
* Nx: Not accessible
* N0: No mets in regional lymph nodes
* N1: Mets in 1-3 lymph nodes
* N2: Mets in >4 regional lymph nodes

Metastasis
* M0: No mets
* M1: Mets

Question 49

Q

Staging
Typing - ICD-O

Answer

A

International Classification for Disease for Oncology, 2 codes:

Topographical code: Describes the anatomical site of origin of the tumor
Morphological code: Describes the cell type (histology) of origin, together with the behavior (B or M)

Both together create a code:
* 0: Benign tumors
* 1: Unspecified, borderline, or uncertain behaviour
* 2: Carcinoma in situ and grade III neoplasia
* 3: Malignant tumors

Question 50

Q

General principles of cancer treatment
Therapeutic intent

Answer

A

There are two different goals, depending on the situation in hand, regarding treatment:
* Curative: The goal is to erradicate the cancer.
* Palliative: The goal is to achieve the best quality of life for both patients and families, through control of physical symptoms, as well as the psychological and social aspects of the situation.

In therapies with curative intent, we accept a relatively high amount of side effects, whereas in palliative intent therapies we put an effort into minimizing the toxicity of treatments.

Question 51

Q

General principles of cancer treatment
Treatment modalities

Answer

A

Treatment of cancers require a multidisciplinary approach involving areas such as surgery, radiation, internal medicine…

Local: Surgery, radiotherapy, ablative approaches

Systemic: Chemotherapy, hormonal therapy, targeted therapy, inmunotherapy

All of these modalities are often used in combination.

Question 52

Q

General principles of cancer treatment
Sequence of therapeutic modalities

Answer

A

Radiation or systemic therapies can be given as…
* Neoadjuvant: Preoperative treatment, used to shrink or downstage the primary tumor before its surgical resection.
* Adjuvant: Postoperative treatment, used after the resection in order to prevent recurrence, and treat cancerous cells that may have travelled to other parts of the body.

These modalities are used for limited disease.

In case of extended or metastised disease options are first, second, third, fourth… lines of systemic treatment (or paliative RT).

Question 53

Q

General principles of cancer treatment
Response to treatment

Answer

A

RECIST criteria
Response Evaluation Criteria in Solid Tumors

These are a set of rules that define when cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment.

Response is typically defined as either:
* Complete response (CR): Disappearance of all lesions
* Partial response (PR): At least 30% decrease in the sum of the longest diameter of lesions.
* Stable disease (SD): Neither PR or PD
* Progressive disease (PD): At least 20% increase in the sum of the longest diameter of the lesions.

Question 54

Q

Principles of surgical treatment in oncology
Therapeutic intent

Answer

A

Surgery for oncologic patients can be performed with curative intent or palliative intent.

Other roles of surgery in the managment of cancer patients include:
* Diagnosis and staging
* Prophylaxis
* Reconstruction
* Oncological emergencies

Question 55

Q

Question 56

Q

Principles of surgical treatment in oncology
Curative surgeries

Answer

A

Removes tumors ‘en bloc’, including the draining lymph nodes, preserving as much tissue as possible.

Can aim for:
* Resection of the primary tumor: Local control.
* Metastasectomy: Resection of isolated metastases, which implies that there are no other sites of metastasic disease. There’s evidence proving this works with patients with either lung or liver mets.
* Debulking operations: Resection of a grand portion of the tumor, but not all of it. Done in ovarian cancer or primary brain tumors…

Question 57

Q

Principles of surgical treatment in oncology
Diagnosis and staging

Answer

A

Surgery can serve to obtain tissue for histological investigation.
* Fine needle aspiration
* Core needle biopsy
* Incisional biopsy
* Excisional biopsy
* Sentinel lymph node biopsy

Question 58

Q

Principles of surgical treatment in oncology
Prophilactic surgery

Answer

A

Examples include:
* Colectomy in patients at risk for Lynch syndrome
* Bilateral mastectomy in women with BRCA mutations.
* Total thyroidectomy at a young age in patients with the RET mutation, at risk for MEN 2a or 2b syndromes
* Orchiopexy in men with undescended testes, as this condition increases the risk for developing seminomma.

Question 59

Q

Principles of surgical treatment in oncology
Palliative surgery

Answer

A

Common indications for paliative surgery include:
* Pain
* Bleeding: Diathermy or laser coagulation
* Obstruction: Placing of plastic or metal stents to relieve the obstruction
* Fistula
* Ascites and pleural effusion: Shunt
* Bone internal fixation on lytic metastases to reduce fractures

Question 60

Q

Principles of surgical treatment in oncology
Reconstructive surgery

Answer

A

Reconstructive surgery can be performed after certain therapies. For example, after a mastectomy.

Plastic surgeons have developed a reconstructive ladder.

Question 61

Q

Principles of surgical treatment in oncology
Oncological emergencies

Answer

A

Particularily in metastasic spinal cord compression, where rapid surgical decompression reduces neurological disability.

Question 62

Q

Principles of radiotherapy
Basic overview

Answer

A

Local therapy involving high energy ionizing radiation to damage DNA, eventually leading to cell death.

RT has two intents: curative or palliative. In both the goal is to damage tumor cells with the maximum accuracy, giving a sufficient dose of radiation, in a certain time, with a minimun load to healthy tissue.

Normal cells are generally better able to repair damage from radiation, because they have certain repair mechanisms that many malignant cells lack, making them more prone to radiation damage. Still, normal tissues have limits on the dose of radiation that they can safely withstand; these determine the maximum dose we can safely administer.

Question 63

Q

Principles of radiotherapy
Therapeutic ratio

Answer

A

Risk-benefit approach to RT planning. We must reach a balance between the probability of radiation induced complications of normal tissue and the probability of tumor control.

We optimize this ratio by minimizing the dose to normal tissues, while maximizing the dose to the tumor target, with special dose-shaping techniques. Often, we fraction the dose of radiation into smaller daily doses, as it is proven that this allows normal tissues to repair themselves, so they are able to withstand the treatment.

Question 64

Q

Principles of radiotherapy
Sources of radiation

Answer

A

Gamma rays
Photons (linear accelerated)
Neutrons/protons (cyclotron)

Answer 63

A

EBRT: External beam radiotherapy
Brachyterapy
IORT: Intraoperative radiation therapy
Radionuclide therapy

Answer 64

A

Delivers radiation from a distance, coming from a source that is outside the patient.

Answer 65

A

A sealed radionuclide source is placed directly into a tumor or body cavity to deliver localized radiotherapy. The radiation is often active across a relatively short distance.

With this, we are able to deliver high doses of RT to the tumor, reducing the dose to the surrounding healthy tissue.

This therapy is mainly used in prostate and gynaechological cancers.

Answer 66

A

Delivery of radiation at the time of the surgery, which allows sparing sensitive structures around. A single fraction treatment is used.

Most used in pelvic and abdominal malignancies.

It is rarely sufficient for tumor control, and so it is often preceded or followed by additional EBRT.

Answer 67

A

Orally or injected. The substance is then absorbed by a particular tissue that preferably accumulates a specific isotope, leaving other tissues unaffected.

Example: Thyroid absorbs iodine 131

Answer 68

A

If we don’t deliver the full planned dose of RT to a tumor it could fail to control it. At the same time, too much irradiation of normal tissue can lead to serious toxicity.

Treatment planning involves:
1. Localization: Defining the tumor target, its anatomic location and relation to adjacent structures.
2. Patient inmobilization: The patient must be inmobilized during planning and subsequent treatment, in order to ensure that the target is irradiated. Inmobilization uses special devices like pelvic masks, breast boards…
3. Imaging: Mostly CT or MRI. Patient must remain in the treatment position for precise target delineation.
4. Planning (imaging): Use the images obtained to delineate or contour the target volumes and normal structures.
5. Dose and schedule: Total dose of radiation needed to treat a specific tumor in a specific location.

Answer 69

A

Gross tumor volume: The exact tumor and its borders as seen on CT.

Answer 70

A

Clinical target volume: Derives from GTV, including microscopical information about the spread of th tumor, beyond the margins seen on the CT scan.

Answer 71

A

Planning target volume: Uncertainties inn planning or treatment delivry. Accounts for the movement of the patient, inaccuracy of the linear accelerator, and other factors that could affect accuracy.

Answer 72

A

Organs at risk: Delineates healthy organs at risk around the tumor.

Answer 73

A

RT dose for solid tumors is usually 60-80Gy, delivered in multiple fractions of time for the following reasons:
* Allows normal cells to recover from the damage radiation may cause (tumor cells are less efficient at this)
* Allows us to hit tumor cells at specific stages of the cell cycle (radiation causes the most damage during G2 and M phases).

Answer 74

A

Treatment with radiotherapy can be potentiated by other treatment options like chemotherapy (concomitant or sequential), hyperthermia or biological therapies.

Answer 75

A

Acute toxicities: Within < 3 months, generally reversible. Predictable and limited to the area treated.
* Edema
* Nausea and vomiting (abd irradiation)
* Mucositis, mouth sores, xerostomia (head & neck irradiation)
* Esophagitis (thoracic)
* Urinary symptoms
* Dermatitis

Long term toxicity: In > 3 months, generally irreversible. Mainly related to fibrosis of irradiated tissue.
* Infertility
* Cardiotoxicity
* Nephrotoxicity
* Xerostomia
* Osteoradionecrosis
* Transverse myelitis
* Secondary malignancies

Answer 76

A

QT drugs interfere with mitosis, affecting mainly quickly dividing cells, targeting the chemistry of nucleic acids, DNA/RNA production or the mechanics of cell division.

Treatment is often a combination of different QT agents, with different action mechanisms, non overlying toxicity patterns and which target different phases of the cell cycle. All of this is to reduce the possibility of developing resistance.

It is given at repeated regular intervals (cycles), depending on the ability of normal tissue to recover, this should be the shortest time possible.

As it targets cellular division, rapidly dividing tumors are more chemosensitive than slower ones. SCLC > NHL > ovarian cancer. Melanoma and clear cell renal cell carcinoma are chemo-resistant.

Answer 77

A

QT can be used as either:
* Curative therapy: Neoadjuvant or adjuvant therapies
* Palliative therapy: Decrease tumor load and increase life expectancy, without curative intent.

Answer 78

A

Used after definitive treatment (typically surgical excission), with the goal of reducing the risk of relapse from micro-metastasic disease.

Based on: tumor staging and performance status (age, comorbidities).

Typical adjuvant chemo is given to breast, colorectal, ovarian and lung cancer.

Answer 79

A

The goal is to downstage the tumor before surgical intervention.

Answer 80

A

If QT is too low, treatment won’t be effective, however, if QT dose is excessive, the toxicity will be intolerable for the patient. Hence, the creation of dosing schemes.

We can intensify the regimen by:
* Increasing the dose: May help overcome drug resistance by exposing the ‘resistant’ cell to higher concentratiions of the drug.
* Changing the intertreatment intervals

Answer 81

A

A common classification is according to whether they work on the cell cycle or not, and their mechanism:
* Microtubule inhibitors on mitosis phase
* Antimetabolites affect DNA synthesis
* Topoisomerase inhibitors affect DNA repair
* Cell cycle independent drugs

Answer 82

A

QT focuses on killing rapidly dividing cells, such as cancerous cells. But there are also other healthy cells that may be harmed by QT, which is where toxicities arise.

There are 3 groups:
* Early within hours of QT
* Delayed within days-months
* Late within months-years

Answer 83

A

Nausea and vomiting which can be prevented in 75% my antiemetic drugs. Treatment includes 5HT3 antagonists, dopamine antagonists or benzodiazepines (anticipatory n&v). Some QT drugs are more emetogenic than others.
Anaphylaxis: This can occur with any drug, mostly with taxanes.
Extravasation: When QT passes onto subcutaneous tissues on administration. Causes pain, erythema, inflmmation… If untreated tissues can necrose.
Tumor lysis syndrome: Oncological emergency where rapid cytolisis can cause hyperuricemia, which will lead to renal failure, hyperkalemia (= arrhythmias), hyperphosphatemia with secondary hypocalcemia. Treatment for this includes hydration, allopurinol, urinary alkalization and rasburicase.

Answer 84

A

These are often manifested during the course of chemotherapy.

Predictable: Relatively common SE, dose related and often occur on rapidly dividing normal cells:
* Alopecia and onychodystrophy (brittle nails)
* Myelotoxicity: Myelosuppression that affects all cell lines, depdning on their lifespan. Can lead to infections and febrile neutropenia.
* GIT mucositis from basal epithelial cell and mucosal damage.

Idiosyncratic: Unpredictable side effects, usually rare, unrelated to dose, and tend to be drug specific. They include dermatological, cardiological, neurological, pulmonary and hepatic side effects.

Answer 85

A

Gonadal: May lead to infertility in males (which is why sperm storage is recommended before the begining of treatment), and permanent amenorrhea in females from gonadal failure.
Teratogenicity
Carcinogenicity
Psychiatric dysfunction: Include symptoms of grief

Answer 86

A

Fever > 38ºC with PMN < 500 cells/dl.
Signs and symptoms of infection are often absent, and fever may be the only indication of infection.

Answer 87

A

Early side effect from chemotherapic drugs, caused mainly from triggering the CTZ (chemoreceptor trigger zone) and through the GIT by causing serotonin release through the vagus nerve.

Acute: 5HT3 antagonists
Delayed: Dopamine antagonists
Anticipatory: Benzodiacepines

Answer 88

A

Important in the managment of hormone-dependent cancers. Its aim is to reduce circulating levels of hormones that promote tumor growth, or to block hormone binding to its receptors within the tumor cell.

Answer 89

A

Endocrine responsive tumors include:
* Breast cancer (anti-estrogen; HER2+, ER+, PR+)
* Endometrial cancer (progesterone)
* Prostate cancer (androgen blockade)
* Thyroid cancer (thyroxine supresses TSH)
* Carcinoid tumors
* Neuroendocrine tumors
* Renal cancer
* Meningioma

Answer 90

A

We must determine which patients could benefit from hormonal therapy, by predicting how the tumor will respond to such treatment.

Ex. for breast cancer the most widely used predictor is the estrogen receptor (ER), 2/3 of ER+ breast cancers respond to hormone manipulation; less than 10% of ER- respond. There will be a higher rate of response in tumors that are double positive (ER+ and PR+)

Answer 91

A

Targeted therapies are drugs that stop the cancer from growing by interfering with specific molecules (targets) involved in the process of growth, progression and spread.

It is often administered with chemotherapy or radiotherapy.

In comparison to conventional chemotherapy, which has a non-specific toxic effect on both tumoral and healthy cells, targeted therapy specifically kills malignant cells, which minimizes the damage to the rest of the tissues.

Answer 92

A

TT works by targeting specific genes or proteins from the tumor cells, or cells related to cancer growth, like blood vessel cells.

Two main kinds of target therapy:
* Small molecule drugs: They enter cells and block specific enzyme pathways and receptors.
* Monoclonal antibodies: Do not enter cells, rather they affect targets outside of cells or on their surface.

Examples:

Tyrosine kinase inhibitors: Prevent intracellular signal transduction.
Hormonal agents (GnRH antagonists/agonists, non steroid antiandrogens): Breast and prostate cancer, targets ligand synthesis or intracellular hormonal tumor receptors
Monoclonal antibodies: Trastuzumab is a humanized Ig against HER2/neu; Rituximab against CD20 Ag in B cells

Answer 93

A

Artificial stimulation of the inmune system to attack tumor antigens actively (activating the host’s inmune system to induce its own response, which will induce inmunological memory) or passively (administration of monoclonal antibodies, checkpoint inhibitors or cytokines, to generate an inmune response against the cancer, without generating inmunological memory).

There’s also a non specific inmunotherapy which coordinates a general inmune response, not specific to a certain cancer. This can be achieved through the administration of cytokines like IL2 or interferons.

Answer 94

A

Checkpoint inhibitors: PD1 and PD1 ligands, CTLA4
Manipulating T cells ex vivo to make them more reactive to specific antigens
Agonism of costimulatory receptors (preclincal models or early phases of clinical development)
Oncolytic virus: Viruses engineered to infect cancer cells, to promote presentation of tumor associated antigens, activate ‘danger signals’ to induce cancer cell destruction.
Vaccines: Sipuleucel-T is the only vaccine based therapy currently approved for advanced cancer, used to target prostatic acid phosphatase in castrate resistant prostate adenocarcinoma. BCG used in the treatment of superficial bladder cancer.

Answer 95

A

Most common side effects include:
* Skin reactions: Erythema, blisters, dryness and phototoxicity
* Flu like reactions: Fatigue, fever, chills… Especially in non specific inmunotherapies and oncolytic virus therapy
* Autoinmune pneumonitis
* Hypophysitis
* Hepatotoxicity

Answer 96

A

Additional management patients requiee to manage cancer symptoms or adverse effects from associated therapies.

Answer 97

A

Antiemetics for nausea and vomiting, which occur in 2/3 of patients.
Analgesics: ~70% of cancer patients experience severe pain during the course of the disease, so they enter the ‘analgesic ladder’: 1. Non opioid drugs 2. Weak opioids (codeine, tramadol…) 3. Strong opioids (morphine, oxycodone, transdermal fentanyl)
Constipation may be avoided by encouraging mobilisation and improval of diet and fluid intake. Opioids must be taken with a laxative and stool softener. Enemas can be done on patients with impacted stools.
Diarrhea is managed with loperamide and hydration monitoring
Anorexia and cachexia has no specific treatment, although they may be managed with the help of a dietitian. Possible causes must be analysed.
Dyspnea may be treated with ATBs if related to infection, drainage of pleural/pericardial effusion, transfusions (anemia)….

Answer 98

A

Patients are expected to have low WBC 10-14 days after chemo. In case of fever, they are neutropenic and should be treated inmediately. Overwhelming sepsis could be fatal.

Treatment includes broad spectrum ATBs including antipseudomonas and antifungals.

Mucositis and older age increase the risk of septicemia.

Answer 99

A

Proteins that promote wbc production. CSF shots prevent patients from developing side effects from chemotherapy like infections or febrile neutropenia.

Adverse effects: Low fever, malaise and bone pain

Answer 100

A

Adjuvant psychological aid could significantly reduce a patient’s anxiety and depression.

Answer 101

A

Affects 70% of cancer patients. Also a feared symptom of advanced malignancies, thus also related to emotional or psychological components that may intensify physical pain.

Acute pain: Caused by injuries, lasts a short time
Chronic pain: Often caused by nerve changes (pressure on bones or nerves from tumor, or side effects of chemicals produced by treatment). Lasts a long time after an injury or after treatment is over.

Answer 102

A

Analgesic ladder
1. Non opioid drugs: Paracetamol, aspirin, NSAIDs, regularly
2. Weak opioids: Codeine, tramadol, dextropropoxyphene, combinations with paracetamol
3. Strong opioids: Morphine, diamorphine, hydromorphine, oxycodone, transdermal fentanyl

Morphine is the most commonly used strong opioid. Starting dose from 5-10mg/day and shall be increased depending on the patient’s needs.

Pain surgery: In patients with long life expectancy and excellent performance status where non invasive analgesics have failed, or when selected therapy results in intolerabl side effects.

Answer 103

A

Tells us about the spread of cancer in the body, through physical examination, imagin, lab tests and biopsies, in order so we can plan treatment and estimate the prognosis.

TNM
* T: Extent of tumor 1-4
* N: Regional lymph node involvement
* M: Occurence of metastasis

cTNM - clinical, pTNM - pathological, and ypTNM is after neoadjuvant treatment (re-staging).

Answer 104

A

We have post treatment surveillance through medical checkups, physical exams, blood tests, scans… The objective is to identify disease recurrence, met spread or development of other cancers, early.

Answer 105

A

Objective response: Measured radiologically using reevaluation criteria RECIST
Subjective response: Mostly used in palliative treatment. Asseses whether patient percieves an improvement in symptoms, comparing to side effects (quality of life).

Answer 106

A

Complete response: Disappearance of all target lesions
Partial response: >30% decrease in the sum of diameters of all lesions.
Stable disease: No change
Progressive disease: >20% increase in sum of diameters, reference the smallest sod taken

Answer 107

A

Measures a patient’s functional capacity based on their general health. Has been found to predict survival in patients with cancer, and may influence in treatment decisions.

For example, patients with a score of 3 or 4 (0-4) are not offered chemotherapy, as it may shorten their survival.

0: Normal activity
1: Symptomatic and ambulatory; cares for self
2: Ambulatory > 50% of time; occasional assistance
3: Ambulatory < 50%; nursing care needed
4: Bedridden

Answer 108

A

These can often serve as independent pronostic factors.

Dyspnea: Strongly and inversely related to survival in terminally ill cancer patients.
Cachexia: Complex metabolic syndrome related to underlying illness. Loss of muscle with or without fatloss. Weight loss > 5% body weight or BMI < 20%
Anorexia
Fatigue
Dysphagia…

More than 40% of cancer patients develop signs of malnutrition during treatment, and abour 20% of them die from its complications.

Answer 109

A

Treatment provided to critically ill patients in a situation where curative treatment has been discontinued, and we have shifted to a comfort care.

The goal is preventing and relieving suffering, as well as supporting the best quality of life possible.

Goals:
* Symptoms control
* Psychological and emotional support
* Family support
* Bereavement support

Answer 110

A

The goal is to reduce suffering, allowing a peaceful and dignified death.

Review medications: Polypharmacy is common in cancer patients, especially in those at the end of ther life. This may be a burden for many. Some of these drugs no longer suppose a therapeutic benefit.
Root of drugs administration: Ensuring timely access to needed medications. Some may not be able to take meds by mouth, consider non oral.
Managing specific symptoms like pain, dyspnea, nausea, delirium, anxiety, seizures…

Palliative sedation: Using non opioid drugs to control refractory symptoms that have been assessed and treated by an interdisciplinary team and not responded to conventional symptom management.

Answer 111

A

Care for terminally ill patients with life expectancy < 6 months, providing care and support to patients and families, focusing on confort over cure.

Focus on pain management, with psychological and spiritual care.

Answer 112

A

Helps patients and families overcome barriers to access services like transport arrangement, financial assistance…

Answer 113

A

Health care professionals should explain the changes that are to happen in cognition and physical function before they occurr, in an attempt to alleviate distress and prevent panic.

Answer 114

A

Therapies designed to help build strength, endurance, reduce stress, regain energy and independence… This reduces morbidity, fraility, distress… and increases quality of life.

Physical: Personalised physical exercise programs to reduce fatigue and increase physical function.
Social: Oncological social workers are here to provide information on resources, medical and insurance coverage (cancer patients often face financial difficulties, after years dealing with the disease, especially with insurance, as well as employement problems and lower social functioning).
Psychological: Cancer patients face a number of psychological difficulties, such as depression, anxiety, fatigue, cognitive limitations, sleep problems, etc. It is part of the rehabilitation programme to provide psychiatrical/psychological help to aid with these problems.

Answer 115

A

When giving bad news, we shouldn’t be protecting the patient from the truth, rather than so, we should try to explain what is happening in the most calm and empathic way possible, letting them space and time to accept what news they’ve received.

It is helpfull to follow a linear approach:
1. Preparation for disclosure: Set a quiet and private space where you can speak freely for a sufficient amount of time. Find out how much the patient already knows and wants to know, by using open questions such as ‘what have doctors told you so far?’.
2. Disclosure: Sharing the news using clear and direct language, avoiding clinical terminology that could be missunderstood, making sure the patient and the family understand. It is good to allow the patient some time and let them respond.
3. Follow up: Patients often react to the bad news with emotion, which we shall expect and be prepared for. In this step we must answer any questions the patient or family have and discuss the following steps or plan. This is an important part, as it makes the future less scary for the patient if they know there’s a plan. This doesn’t mean that in this moment we must determine all aspects of treatment and future procedures, it may as well just be discussing following check ups or tests. Patients could become overwhelmed with this part, so it is best to ask if they are okay with discussing the next steps of the process.

Answer 116

A

Often related to history of mood disorders, substance abuse, previous cancer or its treatment, younger age, low social support, low expectation of successful treatment outcome…

Stress may contribute to worsen anorexia, fatigue, decreased libido, weight loss, insomnia or suicidal ideation.

Adjuvant psychological intervention may help in reducing these problems like depression or anxiety, however if it were not enough, other resources such as medicaments or support groups may be useful.

Answer 117

A

They generally affect adults. May lead to:
* Lazarus syndrome: Difficulty in returning back to normal life
* Damocles syndrome: Fear of recurrence and terror of minor symptoms
* Survivor syndrome: Guilt about surviving whilst others have died

Answer 118

A

Stages of grief:
1. Denial
2. Anger
3. Bargaining
4. Depression
5. Acceptance

Answer 119

A

Plan developed in oncology after completion of treatment, to assure proper transition from oncolgy to the follow up care.

Every cancer survivor receives a follow up care plan containing a summary of their treatment, along with recommendations for follow up care. This plan is based on the type of cancer and treatment.

Goals:
* Ensure remission (surveillance)
* Evaluate late toxicities
* Psychological rehabilitation
* Lifestyle adjustment
* Education

Timing: Generally, people have follow up appointments every 3-4 months in the first 2-3 years, and once or twice a year after that.

Answer 120

A

When there are subclinical numbers of leukemic cells remaining in the a patient, after reaching complete remission, but are below the limits of detection of conventional methods, which results in relapse of the disease.

MRD can be detected with more sensitive assays, are highly prognostic, and correlate with relapse rates. We use these assays in children with acute lymphoblastic leukemia but also recently increasing in adults as well.

Techniques used for detection of residual disease include cytogenetics, FISH, PCR, Southern blotting…

Answer 121

A

It’s the return of a disease or its signs and symptoms after a period of improvement, mostly ocurring in adults. The relapsing disease is often more resistant than the primary, and also puts the patient in a higher risk of future relapses.

Answer 122

A

Complete response
Partial response
Stable disease
Progressive disease

By imaging we can determine:
* Measurable disease: At least 1 lesion that can be accurately measured, longest diameter > 20mm in conventional techniques, > 10mm on spiral CT.
* Non measurable disease: < 20mm/10mm
* Target lesions: Lesions measured and recorded at baseline, selected due to their size and suitability for accurate repeated measurements.
* Non target lesions: Any lesion at the site of the disease not classified as target lesion. Identified at baseline, but not measured. Follow up takes into account whether or not they are still present.

Answer 123

A

> 38ºC for >1h and absolute neutrophil count < 500 cells/microL

Patients are expected to have low white blood cell count during the 10-14 days after chemotherapy; in case fever develops within those days, they are considered neutropenic patients and should be treated inmediately for infection, as they are at risk of developing severe sepsis, which could be fatal.

Causes for fever in neutropenic patients may be:
* Microbiologically documented infection
* Clinically documented infection
* Unexplained fever

Dx: hemmocultures, PCR testing, inflammatory markers, chest Xray, abdominal US, CT

Tx: Hygiene measures, broad spectrum ATB (including antipseudomonics), antifungals.

Answer 124

A

Bleeding is a common problem in cancer patients, that could be related to local tumor invasion, angiogenesis, systemic effects of cancer or even anti-cancer treatments. Some medications can also exacerbate existing bleeds.

Thrombocytopenia, which is frequent in blood cancers, conforms an elevated risk of bleeding, once platelets fall below 10-20x10^9/L. Below these levels, prophylactic platelet transfusions are performed, IL-11 is administered. EPO analogues are proving more efficient.

Answer 125

A

Cancer patients are at an elevated risk of developing thrombosis due to effects on blood pressure, venous stasis, or even due to tumor procoagulants like CF10, C, S.

Low molecular weight heparin is more effective than warfarin in the prophylaxis of thromboembolisms.

Answer 126

A

Effusions are often the first manifestation of some cancers.

Pleural effusion: Mostly due to lung and breast cancer. Causes dyspnea, cough and chest pain. Exudates (high LDH/proteins, low glucose) and blood may be present.
Pericardial effusion: May lead to cardiac tamponade, with decreased heart sounds, low blood pressure and distension of the jugular blood vessels (Beck’s triad)
Ascites: Often related to ovarian, pancreatic, stomach, colon, breast or lung cancer. Causes belly pain, leg edema, dyspnea and ‘squashed stomach syndrome’ that leads to anorexia. Treatment includes diuretics or peritoneovenous shunt, as with paracentesis fluid often reaccumulates.

Answer 127

A

Malignant hypercalcemia
Tumor lysis syndrome

Answer 128

A

In up to 10% of complicated cancer patients. Associated to breast, myeloma and squamous cell carcinoma of the lung.

Mechanisms involved in pathogenesis:
* Increased bone resorption due to bone metastasis. The tumor produces cytokines and necrosis factors that contribute to osteolysis, which eventually increases calcium concentrations.
* Systemic release of humoral hypercalcemic factors: Parathyroid hormone related pepetide is the most common cause in the absence of bone mets.

Symptoms depend on the level of hypercalcemia:
* Mild to moderate (2,5-2,9 mmol/l): Fatigue, anorexia, nausea, vomiting, bone pain… Bradycardia, short QT, wide T wave, prolonged PR and arrythmias or cardiac arrest.
* Severe (>3,0mmol/l): Neurological symptoms like confusion, sleepiness, lethargy, coma.

Treated with calcitonin, intravenous fluids and bisphosphonates.

Answer 129

A

Occurs due to the sudden release of an elevated number of intracellular components, due to the killing of tumoral cells by chemotherapy drugs. These cause an increase in K+, phosphates and uric acid, and decreases calcium in the bloodstream, which may induce acute tubular necrosis, arrythmias and tetany.

PUKE calcium: Phosphates, Uric acid, K are Elevated, Calcium is decreased.

Answer 130

A

A mass compresses the spinal chord. Can happen anywhere along it, most frequently in the thoracic region. First presentation in 5% of cancer patients.

Reasons include:
* Mets to the vertebral bodies
* Vascular compresion

Symptoms: Always consider SCC as an option when cancer patients present back pain, and perform an Xray to exclude. Symptoms will vary depending on the location.
* Localized bone pain and tenderness
* Radicular pain
* Motor and sensory defficiency
* Bladder and bowel dysfunction

Early diagnosis is critical. Delay can lead to irreversible consequences:
* Neurological examination
* CT, MRI or x-ray

Treatment must begin asap, with corticosteroids (peritumoral edema), surgical decompression and radiation therapy, which is in many cases the standard treatment, as effective as surgery. Chemotherapy and hormonal therapy may also be appropriate in certain situations.

Answer 131

A

Increased ICP due to tumor mass or met to the brain, with adjacent edema or meningeal infiltration.

ICP increases because these tumors are mass occupying lesions and, since the brain is inside the skull, which cannot expand in response to an increase in volume, pressure increases. It may also be due to hydrocephalus if the tumors obstruct cerebrospinal fluid drainage.

Symptoms include headache, nausea and vomits, seizures, behavioral changes, focal changes, and pappiledema. Increased ICP may lead to brain herniation.

Diagnosis due to clinical signs, brain CT or MRI, stereotactic biopsy.

Emergency treatment must be done to prevent brain herniation: mannitol, corticosteroids, brain tumor debulking. Radiotherapy or neurosurgery can be considered depending on severity.

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