CBL: Malignancies Flashcards
1
Q
Li Fraumeni Syndrome - what is this? - what mutation does it involve?
A
Li-Fraumeni syndrome is a rare disorder that greatly increases the risk of developing several types of cancer, particularly in children and young adults
Mutation: TP53
2
Q
Li Fraumeni Syndrome - when to consider (ages, FHx)
A
Consider if: - sarcoma <45 years old and 1st degree relative with any cancer <45 years old or sarcoma at any time
3
Q
Li Fraumeni Syndrome 1. What cancers does it predispose to? 2. What management is there for a person with that syndrome?
A
- Rhabdomyosarcoma, ALL, breast Ca, brain tumours, adenocorticoid tumours, colorectal cancer 2. Genetic counselling and regular screening for cancers
4
Q
Leukaemia presentation (symptoms)
A
- General malaise - Intermittent fevers Symptoms secondary to cytopenias: -Bleeding(mucosal), bruising, petechial rash - Anaemia, SOB, fainting, fatigue - Infection ; bacterial, fungal, viral -Pain (Bone, Joints, Abdomen, Chest, Head) - Lymphadenopathy & hepatosplenomegaly - Skin nodules
5
Q
Leukaemia: What happens in the bone marrow and what does it do to the cells produced there?
A
Disruption in the regulation and proliferation of lymphoid precursor cells in the bone marrow leads to excessive production of immature blast cells and drop in the other three cell lines
6
Q
What cancer is the most common among children?
A
Acute Lymphoblastic Leukaemia (ALL)
7
Q
4 most common cancers in children are…
A
- Leukaemia (Acute Lymphoblastic Leukaemia)
- Brain and spinal tumours
(e. g. medulloblastoma, neuroblastoma, glioma) - Nephroblastoma (Wilm’s tumour)
- Lymphoma
8
Q
Which are two sites difficult to treat in leukaemia?
Why?
A
Testicles -> due to blood-testicular barrier
CNS -> due to blood-brain barrier
9
Q
- What’s tumour lysis syndrome? What happens?
A
- Tumour lysis syndrome - metabolic abnormalities resulting from a large number of tumour cells being killed off (lysed) -> cancer cells will release their content into blood stream
Happens in cancers that respond well to chemotherapy (e.g. leukaemia and lymphomas)
large amounts of: phosphorus, potassium and calcium leading to potential kidney damage
10
Q
Complications of tumour lysis syndrome
A
nausea and vomiting, but more seriously acute uric acid nephropathy, acute kidney failure, seizures, cardiac arrhythmias, and death
11
Q
Prevention of tumour lysis syndrome
- supportive
- drugs (two)
A
- prophylactic oral or IV allopurinol (a xanthine oxidase inhibitor à uric acid (following cell lysis) formation prevented
- IV hydration to maintain high urine output (> 2.5 L/day)
- Rasburicase is an alternative to allopurinol (reserved for people who are high-risk in developing TLS) àIt is a synthetic urate oxidase enzyme àacts by degrading uric acid
12
Q
Leukaemia management:
Immediate/supportive, if:
- if WBCs are very high
- mass in mediastinum
- infection
A
Leukaemia management:
Immediate/supportive:
- Stabilise unwell child
- Hyperhydration -> if WBCs is very high -> in order to prevent hyperviscosity
- If a mass present in mediastinum and airways are at risk to be compromised -> steroids
- If infection/ sepsis -> antibiotics
13
Q
Drugs used in chemotherapy for Leukaemia
A
Leukaemia management:
Drugs used in chemotherapy:
- 3 or 4 drug depending on risk group
(Dexamethasone, Vincristine, Asparaginase +/- Doxorubicin)
14
Q
Leukaemia management:
- Simply outline what’s the main mode of Rx and supportive care
- is radiotherapy used?
A
- chemotherapy -> given IV, orally, and intra-thecally (into the CSF
- blood products(red cells, platelets)
- prophylactic anti-fungal therapy throughout treatment
*There is no role for radiotherapy in the management of ALL
15
Q
Do we use cranial radiation (prophylactic) in the management of Leukaemia?
A
IT Methotrexate replaced prophylactic cranial RT
16
Q
What medications are used in the ‘maintenance’ therapy for leukaemia?
A
MTX & Mercaptopurine +/- Steroids & Vincristine
17
Q
How long is ‘maintenance’ therapy for Leukaemia?
A
girls -> 2 year
boys -> 3 years
18
Q
Red flags for symtpoms (suspicion of leukaemia)
A
- Non-tender, firm or hard LN
- LN > 2cm
- Progressively enlarging
- Features of ill-health, fever or weight loss
- Pallor
- Unexplained bruising
- Hepatosplenomegaly
- Axillary nodes involved
–(in absence of local infection or dermatitis)
•Supraclavicular nodes involved
19
Q
Risk factors for the development of Lymphoma
A
- being immunocompromised (transplant recipients)
- Epstein-Barr virus (EBV)
- past treatment for other cancers
20
Q
Lymphoma
- what to look for in Hx
- what are ‘B symptoms’?
- non-specific symptoms
A
- a visible or palpable mass
- “B symptoms” such as:
- Weight loss
- Night sweats
- Fevers
- Non-specific symptoms of malignancy: such as lethargy and anorexia
21
Q
Why there may be an airway compromise in Lymphoma?
A
- Mediastinal lymphadenopathy
- superior vena cava obstrution
Presentation: cough, wheeze, difficulty in breathing
22
Q
Investigations for Lymphoma (and the reason behind them)
Bloods
A
- FBC -> to exclude infection
- U&Es -> to investigate for tumour lysis syndrome
- LDH -> lactate dehydrogenase -> usually elevated
23
Q
Investigations for Lymphoma
(and reason behind them)
A. Imaging
B. Definitive diagnosis
A
A. Imaging:
- USS -> to identify other nodes and assist in biopsy
- X ray -> to check if there is a mediastinal node involvement
- full CT -> to check for extent of a disease (staging)
B. Definitive:
-Lymph node biopsy
24
Q
Staging of Lymphoma
A
Lymphoma is staged according to how many groups of lymph nodes or organs are involved:
- Stage 1: Disease is present in a single group of lymph nodes or a single organ
- Stage 2: Disease is present in 2 or more groups of lymph nodes or organs on the same side of the diaphragm
- Stage 3: Disease is present in lymph nodes or organs on both sides of the diaphragm
- Stage 4: There is diffuse involvement of lymph nodes and organs such as the liver and bones
25
What's the role of 'B symptoms' in Lymphoma staging?
B symptoms (night sweats, fever, weight-loss) are associated with worse prognosis at each stage of the Ca
26
Immediate treatment of ***Lymphoma*** in cases of:
- airway compromise
- superior vena cava obstruction
- tumour lysis syndrome
* if **airway compromise** = **emergency**. -\> high dose **steroids** and **airway support**
* Superior vena cava obstruction (**SVCO**) -\> **stenting** of veins to keep them patent ( it will usually resolve with treatment of the underlying malignancy)
* **tumour lysis syndrome**, then **hyperhydration** is important -\> **Allopurinol** or **rasburicase** are also used
27
Long-term treatment of **Hodkin's Lymphoma**
Chemotherapy and radiotherapy
***Dacarbazine*** -\> chemotherapy agent
28
**Burkitt Leukaemia/ Lymphoma**
- what mutations are present
- what do they result in
* **Highly aggressive B cell** (CD20 positive)
* **C-****myc** amplification (FISH studies)
* Doubling time: 24-48hrs
29
**Burkitt Lymphoma/ Leukaemia**
- abdominal symptoms
- treatment
- prognosis
* Abdominal disease may present as intussusception
* Treatment with intensive chemotherapy
* 90% patients are cured overall
30
What's a peak incidence of Wilm's tumour?
2-3 years old
\*almost never occur in teenagers or adults
31
Among known factors of nephroblastoma pathology, what two factors may be implicated?
- genetic syndromes
A. Nephrogenic remnants (immature kidney) 1%
B. Mutation of Tumour suppressor gene
C. syndromes, such as **WAGR** (Wilm’s tumour, Aniridia, Genitourinary malformations, and Retardation), **Denys-Drash** and **Beckwith-Wiedemann**
32
Features in the Hx and examination that may suggest a diagnosis of nephroblastoma
- abdominal distention
- palpable mass of one or both kidney
- hypertension
- signs of compression on other abdominal organs (rarely, at very advanced stage)
33
Investigations for neuroblastoma and reason behind them
**Bloods**
- FBCs -\> to investigate for a child's general health
- U&Es -\> to assess the condition of the kidneys
- urinalysis -\> to check for haematuria
34
Investigations for neuroblastoma and reason behind them
**Imaging**
**Definitive diagnosis**
- USS -\> to check for the mass
- CT /MRI-\> to check how advanced a disease is
- biopsy -\> definitive diagnosis
35
Staging in **nephroblastoma**
**Stage****Definition** 1 The tumour is only confined to the kidney and can be completely removed with surgery 2 The tumour has begun to spread beyond the kidney, but can still be completely removed with surgery 3 The tumour cannot be completely surgically resected because it has spread to neighbouring lymph nodes or ruptured before/during surgery 4 There are distant metastases, most commonly to the lungs. 5 There are bilateral tumours (each can be allocated an individual stage)
36
Management of **nephroblastoma**
* **Stage 1** and **2** -\> solely with **surgery (no** additional benefit to giving chemotherapy which has additional risks later in life)
* **Chemotherapy** -\> to reduce the volume of malignant tissue before surgery, or to treat any areas of malignant disease not removed by surgery
37
Surgery in nephroblastoma
- name
- aim
Surgery usually consists of **nephrectomy**, although in bilateral disease there is usually an attempt to preserve as much functioning renal tissue as possible (to avoid the requirement for renal replacement therapy).
38
- Prognosis in **nephroblastoma**
- follow up and why
* Prognosis for even metastatic disease is good, with over 85% of patients expected to be **cured**
* single functioning kidney -\> to protect the remaining kidney (maintain a healthy blood pressure, as well as avoidance of contact sports - abdominal trauma)
* if chemotherapy and/or radiotherapy received -\> follow up long term to monitor for potential late effects, such as **cardiotoxicity**
39
- what tissues are involved in the development of neuroblastoma?
- what location is the most common for its origin?
- neural tissue
- adrenal glands -\> the most common origin location for neuroblastoma development
\*may also develop in neck, chest, abdomen and spine)
40
Symptoms of neuroblastoma
- [bone pain](https://en.wikipedia.org/wiki/Bone_pain)
- lump in the abdomen, neck, or chest
- a painless bluish lump under the skin
- bruising under the eyes
41
Symptoms of neuroblastoma in relation to its location :
abdomen, chest, spinal cord, bone lesions, eyes/orbit, bone marrow
- abdomen -\> distention, constipation
- chest -\> difficulties in breathing
- spinal cord -\> weakness, inability to crawl, stand or walk
- bone lesions -\> pain, limping
- tumour around eyes, orbit -\> bruising and swelling
- bone marrow infiltration -\> pallor and anaemia
42
Treatment options for neuroblastoma (according to 'risk')
* low-risk disease can frequently be [observed without any treatment at all](https://en.wikipedia.org/wiki/Watchful_waiting) or cured with surgery alone
* Intermediate-risk disease is treated with surgery and [chemotherapy](https://en.wikipedia.org/wiki/Chemotherapy)
* High-risk -\>intensive chemotherapy, [surgery](https://en.wikipedia.org/wiki/Surgery), [radiation therapy](https://en.wikipedia.org/wiki/Radiation_therapy), [bone marrow](https://en.wikipedia.org/wiki/Bone_marrow) / [hematopoietic stem cell transplantation](https://en.wikipedia.org/wiki/Hematopoietic_stem_cell_transplantation),[biological-based therapy with 13-*cis*-retinoic acid ([isotretinoin](https://en.wikipedia.org/wiki/Isotretinoin) or Accutane) and antibody therapy
43
What are the risk groups in neuroblastoma?
low, intermediate and high -\> they will determine treatment options and prognosis
Characteristics took into account: patient's age, extent of disease, tumour microscopic appearance, possible genetic mutations
44
Diagnosis of neuroblastoma
Tissue biopsy
45
Treatment options for **gliomas**
Surgery (if possible), radiotherapy and chemotherapy (may be also used)
46
What's prognosis and treatment options for ***Diffuse Intrinsic Pontine Glioma***?
•Diffuse Intrinsic Pontine Glioma (DIPG)
–Cannot resect
–Radiotherapy may slow progression
–Fatal in \>95% (9 months)
47
Treatment options and prognosis for **medulloblastoma**
•**Multi-modal therapy**
–Surgical resection
–Radiotherapy (age dependent)
–Chemotherapy
•Affected by Blood Brain Barrier
**•Prognosis**
–Varies significantly depending on age, mets, histology/ genetic subgroup
48
Some of the side effects of cancer treatment
* Hair loss (Usually temporary)
* Nausea & vomiting
* Anorexia/ poor nutrition
* Weakness/ tiredness/ lethargy
* Blood product requirement (transfusions)
* Immunosuppression (risk of life-threatening infection)
* Mucositis (sore gut)
* Bleeding & clots
* Headaches, seizures & encephalopathy
* Constipation/ileus
* Skin rashes
* **psychological** (isolation, fear, depression)
49
Side effects of chemotherapy with ***Anthracyclines***
(treatment of many cancers)
***Anthracyclines***
–Cardiac impairment
50
Side effects of treatment with ***Cisplatin*** (long term)
***Cisplatin***:
–Hearing impairment
–Renal impairment
–Hypomagnesaemia
- Infertility
51
Side effects of treatment with ***Vincristine***
***Vinca-Alkaloids***: (eg Vincristine)
–Peripheral neuropathy
52
Side effects of treatment with ***Etoposide***
***Topoisoemerase inhibitors***: (eg Etoposide)
–second Leukaemia
53
Side effect of treatment with ***Ifosfamide***
**Ifosfamide**:
–Encephalopathy
–Haemorrhagic cystitis
54
Side effects of a long-term use of steroids in Ca treatment
**•Steroids**
–Avascular necrosis
55
