Ch51 Metastatic and Hematopoietic tumours

Question 1

What is the route of metastatic spread to the brain?

Answer 1

Haematogenous Although local extension can also occur

Question 2

What proportion of patients will have a solitary cerebral metastasis at the time of neurological symptoms?

Answer 2

30%

Question 3

What proportion of solitary brain lesions in patients with a known cancer are mets?

Answer 3

89%

Question 4

What percentage of solitary brain mets occur in the cerebellum?

Answer 4

18% Most common site of solitary brain mets in adults

Question 5

What are the most common primary malignancies the metastasise to the brain in children?

Answer 5

Neuroblastoma Rhabdomyosarcoma Wilm’s tumour

Question 6

What are the commonest cerebral mets?

Answer 6

Lung > Breast > Kidney > GI > Melanoma

Question 7

How do you treat lung mets in the brain?

Answer 7

Most like to tbe small cell lung ca, Surgery only if life threatening mass effect- otherwise radiation as very radiosensitive If multiple mets then whole brain XRT 30Gy in 10 fractions + chemotherapy

Question 8

Which mutation dictates treatment in metastatic melanoma?

Answer 8

BRAF

Question 9

Which brain mets are radiosensitive to whole brain radiotherapy?

Answer 9

Small cell lung Ca Multiple myeloma Leukaemia Lymphoma Germ cell tumours Breast (moderately sensitive)

Question 10

Which brain mets are highly radioresistant?

Answer 10

Mnemonic: SMART Sarcoma Melanoma Adenocarcinoma Renal Thyroid Colon and Non small cell Lung ca (moderately resistant)

Question 11

When would you operate on spinal epidural mets?

Answer 11

Unknown primary and no tissue diagnosis Spinal instability Deficit due to spinal deformity or compression by bone rather than by tumor radio-resistant tumors Progression during XRT Recurrence after maximal XRT Rapid neurologic deterioration

Question 12

Which tumours commonly metastasise to spine?

Answer 12

Lung Breast Prostate Renal Thyroid

Question 13

What medical therapy is available for spinal mets?

Answer 13

Bisphosphonates reduce risk of vertebral compression fractures by 50% Denosumab - a RANK ligand inhibitor Chemo is ineffective for spinal epidural mets

Question 14

What is the evidence supporting surgery in spinal mets?

Answer 14

Patchell et al. demonstrated in a randomised control trial that surgery + XRT had superior 6 month ambulation rates than XRT alone.

Question 15

How do you treat NSCLC?

Answer 15

Treatment of lung primary with resection / XRT / chemo. If histology NSCLC then resection of cerebral met. If small cell then radiotherapy and no need for surgery.

Question 16

Which tumours seed via the CSF?

Answer 16

HGG PNET Ependymoma Choroid plexus papilloma Pineal region tumours Haemangioblastoma Primary CNS Melanoma **These patients need brain and whole spine MRI!

Question 17

What is the prognosis of melanoma with a brain met?

Answer 17

<6 months

Question 18

Where do melanoma mets invade?

Answer 18

Pia and arachnoid. Haemorrhage is common.

Question 19

Why are melanomas hyperdense on CT?

Answer 19

Melanin content. Therefore, also has Low T2 and high T1 signal on MRI.

Question 20

How do you treat a BRAF-mutant melanoma?

Answer 20

Surgery/SRS if <4 mets followed by BRAF inhibitor (e.g. dabrafenib) + Ipilimumab (mAB to CTLA-4). Anti PD-1 mAB is approved for advanced or unresectable melanoma (Pembrolizumab)

Question 21

How do you treat a BRAF-WT melanoma?

Answer 21

Surgery/SRS +/- WBRT

Question 22

What chemotherapy is used in melanoma treatment?

Answer 22

Temozolamide has 20% response rate. Immunotherapies are better = mAb to CTLA-4 (ipilimumab), BRAF (dabrafenib) and PD-1 (Pembroluzimab = programmed cell death-R)

Question 23

Where do metastases usually arise?

Answer 23

At the GM:WM junction resulting in significant WM oedema.

Question 24

What metastatic work up do you perform?

Answer 24

CT-CAP PSA in men Mammogram in women Consider a PET scan if the above are negative

Question 25

What do chromogranin and synaptophysin stain?

Answer 25

Synaptic vesicles. These are markers of neuroendocrine tumours and positive with small cell lung ca. Also CD56 staining is commonly used.

Question 26

Which metastases are commonly haemorrhagic?

Answer 26

Renal cell, melanoma and choriocarcinoma

Question 27

What is the most important prognostic factor in patients with brain mets?

Answer 27

Karnofsky performance score \>70

Question 28

Which mets should receive SRS or surgery?

Answer 28

KPS\>70: If large and accessible then surgery If small or inaccessible then SRS If \>3 then WBRT KPS\<70: Palliative WBRT

Question 29

Do you offer WBRT after small cell lung ca resection?

Answer 29

Yes as micro-metastases are presumed to be present throughout the brain. Deliver 50Gy with a boost to the tumour bed.

Question 30

When do you offer a stereotactic biopsy for a lesion?

Answer 30

Inaccessible lesion or patients not candidates for surgery but a diagnosis is required that cannot be biopsied from any other site.

Question 31

What factors improve prognosis with brain mets?

Answer 31

KPS\>70 Age \<60 years Single met Controlled primary disease with no systemic spread Female

Question 32

Which primaries are most likely to cause leptomeningeal carcinomatosis?

Answer 32

Breast \> Lung \> Melanoma. Also consider lymphoma. Presents with cranial nerve palsies, hydrocephalus and ataxia.

Question 33

What should you send the CSF for in patients with suspected malignancy?

Answer 33

Cytology MC&S Tumour markers (CEA / AFP etc) Protein / Glucose

Question 34

How do you manage patients with suspected MSCC?

Answer 34

Dexamethasone Whole spine MRI or myelogram if MRI contraindicated Whole spine CT where metastatic lesions are. Surgery or Radiotherapy based on pain, stability, neurological deficit.

Question 35

What is the most important prognostic factor for MSCC?

Question 36

Is chemotherapy helpful for MSCC?

Answer 36

No, on the primary disease

Question 37

What are the indications for surgery in MSCC?

Answer 37

Biopsy Stabilisation Bony compression Radio-resistant tumours or progression during XRT Rapid neurological deterioration

Question 38

What are the contraindications to surgery for MSCC?

Answer 38

Radiosensitive tumours Paralysis Survival \<3-4 months Multiple lesions at multiple leves Not fit for surgery

Question 39

What are the medical therapies for MSCC?

Answer 39

Bisphosphonates RANK-Ligand inhibitors e.g. denosumab Radiotherapy - 30Gy over 10 days

Question 40

Which MSCCs should be considered for pre-op embolisation?

Answer 40

Renal cell ca, thyroid ca and hepatocellular ca. Embolisation of the intercostal arteries (care with artery of Adamkiewcz)

Question 41

What are the findings of the Patchell et al 2005 Lancet study for MSCC surgery?

Answer 41

Randomised control trial of surgery+RT vs RT alone. Modest improvement in survival but patients remained ambulant for longer with surgery+RT (122 days compare to 13 days). Stabilisation surgery was better than laminectomy alone.

Question 42

What is multiple myeloma?

Answer 42

A neoplastic clonal expansion of plasma cells in the bone marrow. Characterised by the production of immunoglobulins (IgG or IgA - refered to as M-protein) If only a single lesion is identified in the bone then this is called a plasmacytoma.

Question 43

What features are associated with multiple myeloma?

Answer 43

Immunosuppression due to proliferation of clonal plasma cells Pancytopenia due to bone marrow involvement Pathological fractures and hypercalcaemia due to bone resorption Pain is usually with movement and absent at rest Hyperviscosity syndrome Cryoglobulinaemia Amyloidosis Renal failure due to monoclonal light chains (Bence-Jones proteins)

Question 44

Why do patients with multiple myeloma develop CTS?

Answer 44

Amyloid deposition within the flexor retinaculum

Question 45

How do you investigate a patient with multiple myeloma?

Answer 45

Bence-Jone protein (Kappa / Lambda light chains) Serum protein electrophoresis (M-spike) Free light chain assay Skeletal survey FBC for pancytopenia Renal function tests (Creatinine is prognostic) Bone marrow biopsy (for diagnosis)

Question 46

What are the treatment options for multiple myeloma?

Answer 46

Radiotherapy - very radiosensitive Surgery for instability Early mobilisation Pain control Kyphoplasty Bisphosphonates (pamidronate) Bortezomib (proteosome inhibitor)

Question 47

What proportion of patients with plasmacytomas develop mulitple myeloma?

Answer 47

60% in 5 years and 80% in 10 years

Question 48

Why is kyphoplasty better than vertebroplasty in MM / plasmacytoma?

Answer 48

Reduced potential of spreading neoplastic cells