Lung Ca
- Small cell (20% of lung Ca)
- Aka: oat cell
- 80% of SCLC develope brain mets 2yrs after diagnosis
- A neuroendocrine tumour
- 95% proximal airways
- Younger aged patients (20-60) that other lungs Ca
- Strong association with smoking
- Median survival 6-10 months
- Two stages
- Limited:
- Confined to chest
- Extensive
- Outside of chest
- Treatment
- Very radiosensitive
- Prophylactic cranial irradiation
- dec. incidence of brain mets
- inc. survival (disease free and overall)
- 25Gy/10fractions
- Prophylactic cranial irradiation may be considered part of the standard treatment of patients with what disease
- Small-cell lung carcinoma
- Brain mets
- Life threatening: surgical resection
- Non life threatening: XRT
- Recurrent brain mets
- XRT 20Gy/10 fractions
- Non Small cell (adenoCa, Large cell, Sq Cell, Bronchoalveolar)
- Prognosis better than Small cell
- When metastatic lung ca is suspected in the brain, biopsy lung lesion to r/o sclc before brain biopsy
Melanoma
General
- 5th most common cancer in men, 7th in women.
- Incidence is increasing.
- Metastases sites:
- Skin,
- Retina,
- Brain (10–70%)
- Nail bed.
- The primary site cannot be identified in up to ≈ 14% of cases.
- Extremely difficult to locate primary sites: intraocular, GI mucosa.
- Brain mets in 70–90% of patients who died from melanoma.
- Brain mets
- Typically presents 14 months after diagnosis
Evaluation
- Metastatic melanoma to the brain classically causes pia/arachnoid involvement on imaging. Hemorrhagic involvement is common.
- CT:
- Hyperdense (melanin-has the ability to attract metallic ions)
- MRI:
- T1WI Intense (melanin)
- T2WI hypointense surrounded by intense halo of edema.
Systemic work-up:
- Systemic disease determines ultimate survival
- So systemic search for mets is important:
- CT of chest/abdomen/pelvis & bone scan.
- PET scan > CT for mets anywhere in the body except brain
- Brain: MR I> CT or PET.
Treatment
- Patients with Karnofsky performance scale (KPS) score <70 are likely to be poor surgical candidates. Some key points:
- Patients with rapidly progressive systemic disease: treat the systemic disease with chemotherapy first, before dealing with the brain mets
- Patients without systemic disease and 1–4 mets (not specific for melanoma) are candidates for surgery if all mets are accessible and can all be removed. SRS is an alternative
- Surgical indications
- Patients with 1–4 CNS metastases that can be completely resected when systemic disease is absent or slowly progressive: long-term survival is possible
- Patients with intracranial mets that cannot be completely removed or with uncontrolled systemic disease may be surgical candidates for the following:
- For symptomatic relief: e.g. lesion causing painful pressure
- Life-threatening lesion: e.g. large p-fossa lesion with 4th ventricle compression
- For hemorrhagic lesion causing symptoms by mass effect from the clot
- Whole-brain radiation therapy (WBXRT).
- Melanoma is typically radioresistant.
- WBXRT provides 2–3 month survival benefit and may be considered for palliation in patients with multiple mets that preclude complete excision or SRS.
- Stereotactic radiosurgery (SRS)
- Considered for ≤4 lesions, all ≤ 3cm in diameter, that are surgically inaccessible, with limited or quiescent systemic involvement.
- Relative contraindications: hemorrhagic lesions, lesions with significant mass effect surrounding edema.
- Chemotherapy
- Alkylating agents:
- Dacarbazine,
- Formerly the gold-standard treatment for melanoma.
- About equally as effective as its newer orally administered analog temozolomide (Temodar®).
- Response rate: 10–20%
- Fotemustine
- Appeared promising in phase II trials but only 6% responded in phase III (vs. 0% for dacarbazine)
- Immunotherapy:
- Ipilimumab (Yervoy®):
- Monoclonal antibody against cytotoxic T lymphocyte antigen-4 (CTLA-4) antigen.
- More effective in patients who do not require corticosteroids
- Interleukin-2 (IL-2):
- Has shown minimal activity in brain mets
- Trials have usually excluded patients with untreated or uncontrolled brain mets due to risk of cerebral edema and hemorrhage from capillary leak
- BRAF inhibitors (BRAFi):
- Inhibits BRAF kinase
- A protein that participates in regulation of cell division & differentiation
- Useful in tumors with BRAF oncogene mutation (as opposed to BRAF wildtype) which is common in melanoma
- Dabrafenib:
- Phase II trial (NCT01266967)30
- Vemurafenib:
- Promising results in heavily treated patients.
- Phase II trial (NCT01378975)31
- Anti-PD-1 drug
- Monoclonal antibody to PD-1 programmed cell death receptor
- Pembrolizumab (Keytruda) approved for advanced or unresectable melanoma not responding to other drugs
Outcome
- In a patient with a single brain met (any type) and good Karnofsky performance score (> 70) and no evidence ofextracranial disease, surgery+XRT had a median survival of 40 weeks vs. 15 weeks for XRT alone
- For melanoma, retrospective studies have shown a benefit of treatment with either surgery or SRS only when all brain lesions are completely treated (selection bias possible in these studies)
- Predictors of poor outcome in melanoma:
- > 3 brain mets
- Development of brain mets after the diagnosis ofextracranial disease
- Elevated lactate dehydrogenase > 2× normal
- Presence of bone metastases
- Multiple brain mets and extensive visceral disease
- Median survival for melanoma brain mets is ≤ 6 months
- Brain mets causes death in 94%
- A small group with survival > 3 yrs had a single surgically treated met in the absence ofother visceral lesions
Renal Cell
- aka Hypernephroma.
- Spread to other regions before brain
- Lungs
- Lymph nodes,
- Liver,
- Bone (high affinity for bone),
- Adrenals, and
- Contralateral kidney
- Rarely presents as isolated cerebral metastases
- Presentation
- Hematuria,
- Abdominal pain, and/or
- Abdominal mass on palpation
- Response to XRT is only ≈ 10%
- High risk of bleeding
- See difference between Renal cell ca vs Haemangioblastoma
- Management
- Immune checkpoint inhibitor therapy
- Advanced RCC without brain mets
- Immune checkpoint inhibitor therapy are proven to be effective
- Eg:
- Programmed death cell death protein 1 (PD-1; i.e., nivolumab)
- Programmed death ligand 1 (PD-L1; i.e., atezolizumab) immune checkpoint inhibitor (ICI) therapies
- Cytotoxic T-lymphocyte–associated protein 4 (CTLA4) inhibitor (i.e., ipilimumab)
- Advanced RCC with brain mets
- Damante et al 2023 ICI was associated with improved OSRCC and OSBM in patients with BMs and decreased the probability of BM development in patients with metastatic RCC
Esophageal
- Median survival 4.2 months
- Solitary brain mets surgically treatment
Ovarian cancer
- A rare origin of brain metastasis
- Costello et al 2023: This data is from 48 patients who had surgery and adjuvant chemo (41%) + radiotherapy (84%)
- Median progression-free survival was 12 months
- Median overall survival was 9 months
- On univariate analysis,
- A single BM and no extracranial metastasis conferred a survival benefit,
- Clear cell carcinoma as the primary histology corresponded to worsened OS.
- Multivariable analysis showed that
- Poor prognosis
- Age > 50 years (p = 0.002) and
- > 1 BM (p < 0.001)
- Protective factors
- Surgery + radiotherapy (p = 0.002),
- Surgery + chemotherapy and radiotherapy (p = 0.005),
- Surgery + stereotactic radiosurgery (p = 0.002).
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