Leptomeningeal Carcinomatosis (Leptomeningeal Metastases)¶

VERSION: 1.1 CREATED: January 30, 2026 REVISED: January 30, 2026 STATUS: Draft - Pending Review

DIAGNOSIS: Leptomeningeal Carcinomatosis (Leptomeningeal Metastases)

ICD-10: C79.32 (Secondary malignant neoplasm of cerebral meninges), C79.49 (Secondary malignant neoplasm of other parts of nervous system), C79.31 (Secondary malignant neoplasm of brain — if concurrent parenchymal metastases), G91.0 (Communicating hydrocephalus), G91.1 (Obstructive hydrocephalus), G93.6 (Cerebral edema), G89.3 (Neoplasm-related pain)

SYNONYMS: Leptomeningeal carcinomatosis, leptomeningeal metastases, leptomeningeal disease, LMD, carcinomatous meningitis, neoplastic meningitis, meningeal carcinomatosis, meningeal metastases, CSF metastases, leptomeningeal spread, leptomeningeal involvement, meningeal carcinosis, leptomeningeal seeding, drop metastases, pial metastases, subarachnoid metastases, leptomeningeal tumor, leptomeningeal dissemination, CNS leptomeningeal metastases

SCOPE: Comprehensive management of leptomeningeal carcinomatosis in adults from common solid tumors (breast cancer, non-small cell lung cancer, melanoma) and hematologic malignancies (lymphoma, leukemia). Covers initial evaluation and stabilization, CSF diagnosis (cytology, flow cytometry, cell-free DNA), neuroimaging (gadolinium-enhanced MRI brain and spine), intrathecal chemotherapy (methotrexate, cytarabine, thiotepa) via lumbar puncture or Ommaya reservoir, systemic therapy with CNS penetration, radiation therapy (involved-field, whole-brain, craniospinal), management of hydrocephalus (VP shunt, ETV), steroid management, seizure treatment, pain management, prognostic assessment, and palliative care integration. Excludes primary CNS lymphoma (separate template), primary leptomeningeal gliomatosis, and isolated parenchymal brain metastases without leptomeningeal involvement (see Brain Metastases template).

PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting

═══════════════════════════════════════════════════════════════ SECTION A: ACTION ITEMS ═══════════════════════════════════════════════════════════════

1. LABORATORY WORKUP¶

1A. Essential/Core Labs¶

Test	Rationale	Target Finding	ED	HOSP	OPD	ICU
CBC with differential (CPT 85025)	Baseline hematologic function; chemotherapy candidacy; thrombocytopenia (LP safety, IT chemo); leukocytosis suggesting concurrent infection; lymphopenia from prior treatment	WBC, ANC, platelets within normal limits; ANC >1500 for IT chemotherapy; platelets >50,000 for LP	STAT	STAT	ROUTINE	STAT
CMP (BMP + LFTs) (CPT 80053)	Renal function for methotrexate clearance (IT MTX); hepatic function for systemic therapy dosing; electrolytes (SIADH from CNS disease); glucose for serum:CSF ratio; steroid-induced hyperglycemia	Normal; anticipate glucose elevation with dexamethasone; creatinine clearance >60 for systemic methotrexate	STAT	STAT	ROUTINE	STAT
PT/INR, aPTT (CPT 85610+85730)	Coagulopathy assessment before lumbar puncture; surgical candidacy for Ommaya reservoir placement	INR <1.5 and platelets >50,000 for LP; INR <1.4 for Ommaya placement	STAT	STAT	ROUTINE	STAT
Blood glucose (CPT 82947)	Serum glucose for CSF:serum glucose ratio (low CSF glucose suggests LMD); steroid-induced hyperglycemia baseline	Obtain simultaneously with LP; normal serum glucose; CSF glucose <60% of serum suggests LMD	STAT	STAT	ROUTINE	STAT
LDH (CPT 83615)	Tumor burden marker; elevated in leptomeningeal disease; prognostic marker; CSF LDH also informative	Normal serum; elevated suggests high tumor burden	STAT	ROUTINE	ROUTINE	STAT
Pregnancy test (beta-hCG) (CPT 84703)	Required before IT chemotherapy or radiation; beta-hCG-secreting tumors (rare); treatment planning	Negative; if elevated, consider choriocarcinoma or germ cell tumor as primary	STAT	STAT	ROUTINE	STAT

1B. Extended Workup (Second-line)¶

Test	Rationale	Target Finding	ED	HOSP	OPD	ICU
Tumor markers (CEA, CA 15-3, CA 125, CA 19-9, AFP) (CPT 82378, 86304, 86301, 82105)	Unknown primary evaluation; breast (CA 15-3, CEA), ovarian (CA 125), GI (CEA, CA 19-9), germ cell (AFP); can also be measured in CSF for comparison	Elevations guide primary site evaluation; CSF tumor markers may be elevated in LMD even when serum is normal	-	ROUTINE	ROUTINE	-
HIV, hepatitis B/C (CPT 87389)	Immunosuppression assessment affecting treatment options; primary CNS lymphoma differential; reactivation risk with immunosuppressive therapy	Negative; positive requires hepatitis prophylaxis before chemotherapy	-	ROUTINE	ROUTINE	-
ESR / CRP (CPT 85652+86140)	Infection differential (bacterial or fungal meningitis vs. neoplastic meningitis); inflammatory markers	Normal; elevated may suggest concurrent infection	STAT	ROUTINE	ROUTINE	STAT
Uric acid (CPT 84550)	Tumor lysis risk in hematologic malignancies with high CSF cell counts; baseline before IT chemotherapy	Normal; elevated in hematologic malignancies with high tumor burden	-	ROUTINE	ROUTINE	-
Methotrexate level (CPT 80076)	Required 24-48h after IT methotrexate if concurrent systemic methotrexate; toxicity monitoring; delayed clearance risk	Undetectable at 48h; elevated levels require leucovorin rescue	-	ROUTINE	ROUTINE	-
TSH, free T4 (CPT 84443+84439)	Fatigue differential; hypothyroidism from prior immunotherapy (checkpoint inhibitors); pituitary metastasis	Normal; abnormal may indicate thyroid dysfunction from immunotherapy	-	ROUTINE	ROUTINE	-

1C. Rare/Specialized (Refractory or Atypical)¶

Test	Rationale	Target Finding	ED	HOSP	OPD	ICU
CSF cell-free DNA (cfDNA) / liquid biopsy (CPT 81479)	Emerging diagnostic tool; sensitivity ~80-90% for LMD (higher than cytology); can detect actionable mutations in CSF; monitor treatment response via serial cfDNA levels	Detectable tumor-specific mutations; concordance with primary tumor molecular profile; declining cfDNA suggests treatment response	-	EXT	EXT	-
Next-generation sequencing (NGS) of CSF (CPT 81455)	Identify actionable mutations in CSF when tissue biopsy not feasible; EGFR, ALK, HER2, BRAF, PIK3CA; guide targeted therapy selection	Actionable driver mutations; may differ from primary tumor (clonal evolution)	-	EXT	EXT	-
CSF VEGF level	Elevated in LMD; may serve as biomarker for disease activity; research tool; correlates with clinical outcomes	Elevated (>10 pg/mL suggests LMD); declining levels may indicate treatment response	-	EXT	EXT	-
Paraneoplastic antibody panel (CPT 86235)	If clinical presentation includes features of paraneoplastic syndrome (limbic encephalitis, cerebellar degeneration) coexisting with LMD	Negative; positive identifies concurrent paraneoplastic syndrome requiring different treatment approach	-	EXT	EXT	-
Circulating tumor DNA (ctDNA) - blood (CPT 81479)	Complementary to CSF cfDNA; systemic disease monitoring; may guide systemic therapy when CSF sampling not feasible	Detectable mutations guide therapy; monitor systemic disease burden	-	EXT	EXT	-

2. DIAGNOSTIC IMAGING & STUDIES¶

2A. Essential/First-line¶

Study	Timing	Target Finding	Contraindications	ED	HOSP	OPD	ICU
CT head without contrast (CPT 70450)	Immediate in ED for acute presentation	Mass effect, hydrocephalus (communicating or obstructive), hemorrhage; determines LP safety; midline shift assessment	Pregnancy (benefit outweighs risk in acute setting)	STAT	STAT	-	STAT
MRI brain with and without gadolinium (CPT 70553)	Within 24h; GOLD STANDARD for LMD diagnosis; thin-cut (1mm) 3D T1 post-contrast and FLAIR sequences	Leptomeningeal enhancement (linear, nodular, or combined); cranial nerve enhancement (CN III, V, VII, VIII most common); subependymal enhancement; communicating hydrocephalus; concurrent parenchymal metastases	MRI-incompatible implants; GFR <30 (gadolinium risk); severe claustrophobia	STAT	STAT	URGENT	STAT
MRI total spine with gadolinium (CPT 72156+72157+72158)	Within 24-48h; essential for complete staging; cauda equina and nerve root involvement	Leptomeningeal enhancement along spinal cord surface; nerve root thickening and enhancement (especially cauda equina); intradural nodular deposits; cord compression from epidural extension	Same as brain MRI	-	URGENT	URGENT	-
CT chest/abdomen/pelvis with contrast (CPT 71260+74178)	Within 48h if primary unknown or restaging needed	Primary tumor identification; systemic disease burden; additional metastatic sites; guides systemic treatment options	Contrast allergy; renal impairment (creatinine clearance <30)	URGENT	URGENT	ROUTINE	-
Chest X-ray (CPT 71046)	Immediate if acute presentation	Lung primary (most common solid tumor causing LMD along with breast); pulmonary metastases; aspiration pneumonia if obtunded	Pregnancy (shield abdomen)	STAT	STAT	-	STAT

2B. Extended¶

Study	Timing	Target Finding	Contraindications	ED	HOSP	OPD	ICU
PET/CT (FDG) (CPT 78816)	During hospitalization or outpatient; systemic staging	Primary tumor; additional metastatic disease; leptomeningeal FDG uptake (low sensitivity for LMD but helps identify systemic disease burden)	Uncontrolled diabetes (glucose >200); pregnancy	-	ROUTINE	ROUTINE	-
CT myelography (CPT 72240)	If MRI contraindicated; intrathecal contrast via LP	Filling defects in subarachnoid space; nodular deposits; blockage of CSF flow; nerve root clumping	Same as LP contraindications; contrast allergy	-	ROUTINE	EXT	-
Radionuclide CSF flow study (In-111 DTPA) (CPT 78630)	Before initiating IT chemotherapy; determines CSF flow dynamics	Normal CSF flow pattern; ABNORMAL flow (block at skull base, spinal block, ventricular outlet obstruction) present in 30-70% of LMD patients; blocked flow predicts poor IT chemo distribution and increased toxicity	Active systemic infection; LP contraindications	-	ROUTINE	ROUTINE	-
MRI orbits with gadolinium	If visual symptoms or suspected optic nerve/orbital involvement	Optic nerve enhancement; orbital soft tissue involvement; perineural spread along CN V	Same as brain MRI	-	ROUTINE	ROUTINE	-
ECG (12-lead) (CPT 93000)	Baseline; pre-treatment assessment	QTc for antiemetics and targeted therapies; cardiac function baseline	None	STAT	STAT	ROUTINE	STAT

2C. Rare/Advanced¶

Study	Timing	Target Finding	Contraindications	ED	HOSP	OPD	ICU
MRI brain with 3D FLAIR post-contrast	When standard MRI equivocal; higher sensitivity for subtle leptomeningeal disease	Subarachnoid FLAIR hyperintensity indicating protein-rich CSF or tumor; more sensitive than T1 post-contrast for early/subtle LMD	Same as MRI	-	ROUTINE	ROUTINE	-
CT head post-Ommaya placement	After Ommaya reservoir surgery	Catheter tip position in frontal horn of lateral ventricle; no hemorrhage; no air-fluid level concerning for infection	None	-	STAT	-	-
Stereotactic biopsy of enhancing meninges	When CSF cytology repeatedly negative despite high clinical suspicion and classic MRI findings	Tissue diagnosis confirming leptomeningeal carcinomatosis; histopathology and molecular profiling	Coagulopathy; lesion not safely accessible; poor performance status precluding surgery	-	EXT	EXT	-

LUMBAR PUNCTURE¶

Indication: Primary diagnostic tool for leptomeningeal carcinomatosis; CSF cytology, flow cytometry, cell-free DNA; also therapeutic (IT chemotherapy administration) Timing: URGENT at initial presentation if LMD suspected; repeat LP if first cytology negative (sensitivity improves from ~50% to ~80-90% with repeat) Volume Required: 10-15 mL minimum (larger volumes improve cytology yield); collect from last tube for cytology to minimize traumatic contamination

Study	Rationale	Target Finding	ED	HOSP	OPD	ICU
Opening pressure (CPT 89050)	Elevated ICP common in LMD (30-50% of patients); communicating hydrocephalus assessment; guides need for CSF diversion	10-20 cm H2O normal; >25 cm H2O elevated; >30 cm H2O consider urgent CSF diversion	URGENT	URGENT	ROUTINE	URGENT
CSF cytology (CPT 88104+88112)	GOLD STANDARD for definitive LMD diagnosis; sensitivity ~50% on single LP, improves to ~80-90% with 2-3 repeat LPs; MUST process within 30 minutes (cells degrade rapidly)	Malignant cells present = diagnostic (100% specific); negative does NOT exclude LMD; report includes morphology and cell type	URGENT	URGENT	ROUTINE	URGENT
CSF flow cytometry (CPT 88184+88185)	Higher sensitivity than cytology for hematologic malignancies (lymphoma, leukemia); identifies clonal B-cell or T-cell populations; useful even when cytology is negative	Monoclonal B-cell or aberrant T-cell population; clonal immunoglobulin light chain restriction; abnormal immunophenotype	URGENT	URGENT	ROUTINE	URGENT
CSF protein (CPT 84157)	Elevated in >80% of LMD patients; nonspecific but supports diagnosis; monitor treatment response	Normal 15-45 mg/dL; elevated >50 mg/dL in most LMD; markedly elevated (>100 mg/dL) common; declining with treatment = good sign	URGENT	URGENT	ROUTINE	URGENT
CSF glucose (CPT 82945)	Low CSF glucose (hypoglycorrhachia) present in ~40-60% of LMD; calculate CSF:serum ratio	Normal CSF glucose >40 mg/dL (or >60% of serum); low CSF glucose (<40 or CSF:serum <0.5) supports LMD diagnosis	URGENT	URGENT	ROUTINE	URGENT
CSF cell count with differential (CPT 89051)	Lymphocytic pleocytosis in 40-70% of LMD; distinguish from infectious meningitis; atypical cells on differential	WBC <5 normal; elevated WBC with lymphocytic predominance supports LMD; atypical or malignant cells on differential	URGENT	URGENT	ROUTINE	URGENT
CSF LDH (CPT 83615)	Elevated in LMD; marker of tumor cell turnover in CSF; prognostic; monitor treatment response	Normal CSF LDH <40 U/L; elevated supports LMD; very high levels associated with worse prognosis	URGENT	ROUTINE	ROUTINE	URGENT
CSF tumor markers (CEA, CA 15-3, AFP as guided by primary)	May be elevated in CSF even when cytology is negative; supports diagnosis; monitor treatment response	CSF:serum ratio >1 for tumor markers highly suggestive of LMD; declining with treatment = response	-	ROUTINE	ROUTINE	-
Gram stain and culture (CPT 87070+87205)	Rule out concurrent infectious meningitis (bacterial, fungal); Ommaya reservoir infection	No organisms; positive culture = concurrent infection requiring treatment before IT chemo	URGENT	URGENT	ROUTINE	URGENT
Fungal culture, AFB smear/culture (CPT 87102+87015)	If immunocompromised or clinical suspicion for fungal/TB meningitis mimicking LMD	Negative; positive requires antifungal/antimycobacterial treatment	-	ROUTINE	ROUTINE	-

Special Handling: CSF cytology specimens MUST be processed within 30 minutes of collection (cells degrade rapidly at room temperature); send immediately to cytopathology on ice or in fixative per institutional protocol; last tube typically used for cytology to minimize blood contamination; if flow cytometry ordered, send in separate tube without fixative Contraindications: Significant mass effect with midline shift >5mm; obstructive hydrocephalus (herniation risk); large posterior fossa mass; coagulopathy (INR >1.5 or platelets <50,000); skin infection at LP site; anticoagulation (hold per guidelines before LP)

3. TREATMENT PROTOCOLS¶

3A. Acute/Emergent Treatment¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Dexamethasone	IV/PO	Vasogenic edema from leptomeningeal disease; symptomatic relief of headache, nausea, cranial neuropathies; bridge to definitive treatment	10 mg :: IV :: q6h :: 10 mg IV loading dose, then 4 mg IV/PO q6h; moderate symptoms 4-8 mg/day; severe symptoms/herniation 10 mg IV then 4-8 mg q6h (up to 16-24 mg/day); begin taper once definitive treatment initiated; GI prophylaxis with PPI while on steroids	Active untreated infection; uncontrolled diabetes (relative); GI bleeding (relative); psychosis from prior steroids	Glucose q6h (steroid hyperglycemia); mental status; blood pressure; GI symptoms; signs of infection (immunosuppression)	STAT	STAT	URGENT	STAT
Lorazepam (acute seizure)	IV	Active seizures in setting of leptomeningeal disease with cortical irritation	0.1 mg/kg :: IV :: PRN seizure :: 0.1 mg/kg IV push (max 4 mg per dose); may repeat x1 in 5 min; max 8 mg total; bridge to AED loading	Severe respiratory depression without ventilator support; acute narrow-angle glaucoma	Respiratory status; sedation level; oxygen saturation; blood pressure	STAT	STAT	-	STAT
Levetiracetam (seizure load)	IV	AED loading after benzodiazepine for seizure in LMD; preferred AED in cancer (no CYP interactions with chemotherapy or targeted agents)	1500 mg :: IV :: load :: 1000-1500 mg IV over 15 min; avoid phenytoin/fosphenytoin if possible (CYP interactions with chemotherapy and targeted agents); transition to oral 500-1500 mg BID for maintenance	Renal impairment (dose adjust if CrCl <50); known hypersensitivity	Seizure recurrence; renal function for dose adjustment; behavioral changes	STAT	STAT	-	STAT
Mannitol (acute herniation)	IV	Acute hydrocephalus with herniation signs (pupil asymmetry, posturing, declining GCS)	1 g/kg :: IV :: bolus :: 1-1.5 g/kg IV bolus over 15-20 min; may repeat 0.25-0.5 g/kg q4-6h; bridge to emergent CSF diversion or radiation	CHF; severe renal failure; anuria; severe dehydration	Serum osmolality (keep <320 mOsm/kg); BMP q6h; urine output; ICP if monitored; renal function	STAT	-	-	STAT
Hypertonic saline 23.4% (acute herniation)	IV	Acute herniation from obstructive hydrocephalus due to LMD when mannitol contraindicated or insufficient	30 mL :: IV :: bolus :: 23.4% NaCl 30 mL via central line over 15 min (MUST be central line); alternative: 3% NaCl 250 mL over 30 min (can be peripheral); bridge to emergent CSF diversion	Hypernatremia (Na >160); central pontine myelinolysis risk; 23.4% requires central line	Sodium q2-4h; serum osmolality; neurologic exam; target Na 145-155 mEq/L	STAT	-	-	STAT
Emergent EVD placement	Surgical	Acute obstructive hydrocephalus with declining level of consciousness from LMD blocking CSF pathways	N/A :: Surgical :: procedure :: Emergent neurosurgical consultation for external ventricular drain placement; temporary CSF diversion; can measure ICP continuously	Coagulopathy (correct first); scalp infection at insertion site	ICP monitoring (target <20 mmHg); CSF output; infection surveillance (daily CSF cell count if prolonged)	STAT	STAT	-	STAT
Enoxaparin (DVT prophylaxis)	SC	CNS malignancy with high VTE risk (20-30%); immobility from neurologic deficits	40 mg :: SC :: daily :: Enoxaparin 40 mg SC daily starting within 24-48h unless contraindicated; SCDs immediately on admission; hold 24h before and after LP or IT chemo	Active intracranial hemorrhage; planned LP within 12h; planned Ommaya surgery; CrCl <30 (use heparin instead)	Platelet count; signs of hemorrhage; anti-Xa levels if renal impairment	-	STAT	-	STAT
Heparin (DVT prophylaxis alternative)	SC	VTE prophylaxis when enoxaparin contraindicated (renal impairment CrCl <30)	5000 units :: SC :: q8h :: Heparin 5000 units SC q8h; hold 4h before and after LP or IT chemo; SCDs as adjunct	Active intracranial hemorrhage; planned LP within 4h; planned Ommaya surgery; HIT history	Platelet count (HIT surveillance); signs of hemorrhage	-	STAT	-	STAT
Omeprazole (stress ulcer prophylaxis)	PO/IV	GI protection while on dexamethasone; critical illness with steroid use	20 mg :: PO :: daily :: Omeprazole 20 mg PO daily or pantoprazole 40 mg IV daily if NPO; continue throughout steroid course	Known hypersensitivity; consider C. difficile risk with prolonged PPI use	GI symptoms; consider H. pylori testing if prolonged use	STAT	STAT	ROUTINE	STAT

3B. Definitive/Targeted Treatment¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Intrathecal methotrexate (via Ommaya)	IT	First-line IT chemotherapy for LMD from solid tumors (breast, lung); best evidence base among IT agents	12 mg :: IT :: twice weekly :: 12 mg in 3-5 mL preservative-free normal saline via Ommaya reservoir; twice weekly for 4 weeks (induction), then weekly for 4 weeks (consolidation), then monthly (maintenance); co-administer leucovorin 10 mg PO q6h x 4 doses starting 24h after each IT dose to prevent systemic toxicity	Concurrent high-dose systemic methotrexate (combined toxicity); pre-existing severe leukoencephalopathy; active CNS infection; blocked CSF flow (perform flow study first — blocked flow increases neurotoxicity)	CBC before each dose; renal function (methotrexate clearance); neurologic exam (chemical meningitis, leukoencephalopathy); MRI q6-8 weeks for response and leukoencephalopathy surveillance	-	URGENT	ROUTINE	-
Intrathecal methotrexate (via LP)	IT	IT chemotherapy when Ommaya reservoir not yet placed; initial treatment while awaiting surgery	12 mg :: IT :: per schedule :: 12 mg in 3-5 mL preservative-free normal saline injected slowly via LP; patient lies flat for 1 hour post-injection; same schedule as Ommaya administration; Ommaya preferred for repeated dosing (avoids repeat LPs, more reliable CSF distribution)	Concurrent high-dose systemic methotrexate; pre-existing severe leukoencephalopathy; active CNS infection; blocked CSF flow; coagulopathy; mass effect; skin infection at LP site	CBC before each dose; renal function; neurologic exam; monitor for post-LP headache; CSF leak at puncture site	-	URGENT	ROUTINE	-
Intrathecal cytarabine (liposomal, DepoCyt)	IT	Alternative or second-line IT agent; sustained-release formulation allows less frequent dosing; solid tumors and hematologic malignancies	50 mg :: IT :: q2 weeks :: 50 mg liposomal cytarabine (DepoCyt) IT via Ommaya or LP q2 weeks for 5 doses (induction), then q4 weeks (maintenance); co-administer dexamethasone 4 mg PO BID for 5 days starting day of injection (prevents chemical arachnoiditis); NOTE: DepoCyt supply has been intermittent — verify availability	Known hypersensitivity; active meningeal infection; blocked CSF flow	CBC before each dose; neurologic exam (chemical arachnoiditis occurs in 20-40% without dex prophylaxis); lumbar symptoms; fever; MRI q6-8 weeks	-	URGENT	ROUTINE	-
Intrathecal thiotepa	IT	Third-line IT agent; used when methotrexate and cytarabine not tolerated or disease refractory; breast cancer LMD	10 mg :: IT :: twice weekly :: 10 mg in 3-5 mL preservative-free normal saline via Ommaya reservoir; twice weekly during induction; taper to weekly then monthly per response	Active infection; severe myelosuppression (ANC <500); blocked CSF flow	CBC (myelosuppression more common than with MTX); neurologic exam; renal function	-	URGENT	ROUTINE	-
Ommaya reservoir placement	Surgical	Repeated IT chemotherapy delivery; avoids multiple lumbar punctures; more reliable drug distribution to ventricles and subarachnoid space; can also be used for CSF drainage	N/A :: Surgical :: procedure :: Neurosurgery for subcutaneous reservoir connected to ventricular catheter; catheter tip in frontal horn of ipsilateral lateral ventricle; post-op CT to confirm placement before use; typically ready for use 48-72h post-placement	Coagulopathy (INR >1.4, platelets <100,000); overlying scalp infection; severe hydrocephalus (may need VP shunt instead); very poor performance status (KPS <40) precluding surgery	Post-op CT for catheter position; wound site (infection, CSF leak); daily neurologic checks post-op; long-term: site infection surveillance at each access	-	URGENT	ROUTINE	-
Involved-field radiation therapy	XRT	Symptomatic bulky leptomeningeal disease; cranial nerve deficits; cauda equina syndrome; CSF flow block requiring focal radiation to restore flow	30 Gy :: XRT :: 10 fractions :: Focal RT to symptomatic sites; typically 30 Gy in 10 fractions to affected region; may treat cranial nerves, cauda equina, or sites of CSF block; concurrent IT chemo if CSF flow adequate	Prior radiation to same field (cumulative dose limits); very poor performance status; extensive disease making focal approach impractical	Neurologic exam; MRI post-radiation (6-8 weeks); blood counts if concurrent chemotherapy; late effects (radiation necrosis, myelopathy)	-	URGENT	ROUTINE	-
Whole-brain radiation therapy (WBRT)	XRT	Diffuse cerebral leptomeningeal disease; concurrent multiple parenchymal brain metastases; symptomatic cranial neuropathies not responsive to steroids	30 Gy :: XRT :: 10 fractions :: Standard: 30 Gy in 10 fractions (3 Gy/fraction); poor prognosis: 20 Gy in 5 fractions; hippocampal avoidance (HA-WBRT) when feasible + memantine; consider concurrent IT chemo (typically given on non-radiation days)	Prior WBRT (re-irradiation has higher toxicity risk); severe leukoencephalopathy; very poor prognosis (KPS <40) where radiation unlikely to provide benefit	Neurologic exam weekly during treatment; CBC weekly; cognitive function post-treatment; MRI 4-6 weeks post-WBRT; memantine for neuroprotection	-	URGENT	ROUTINE	-
Craniospinal irradiation (CSI)	XRT	Extensive leptomeningeal disease involving brain and full spinal axis; hematologic malignancies with CSF involvement; selected solid tumors with diffuse leptomeningeal seeding	30-36 Gy :: XRT :: 15-20 fractions :: 30-36 Gy to craniospinal axis in 1.5-1.8 Gy fractions; significant myelosuppression expected; requires good performance status (KPS >=60); proton therapy preferred when available (less bone marrow toxicity)	Severe cytopenias (ANC <1000, platelets <75,000); very poor performance status; recent myelosuppressive chemotherapy without adequate recovery; pregnancy	CBC 2x/week during treatment; weekly neurologic exam; renal function; esophagitis and nausea management; delayed: myelosuppression nadir at 2-4 weeks post-CSI	-	ROUTINE	ROUTINE	-
Osimertinib (EGFR+ NSCLC)	PO	EGFR-mutant NSCLC with leptomeningeal disease; excellent CSF penetration	80 mg :: PO :: daily :: Osimertinib 80 mg PO daily; CSF penetration ~2-7% (sufficient for activity); may increase to 160 mg daily for LMD per BLOOM trial; continue until progression or intolerance	Interstitial lung disease/pneumonitis; QTc >500 ms; severe hepatic impairment	ECG at baseline and monthly (QTc); LFTs monthly; ophthalmologic exam if visual symptoms; CBC; monitor for pneumonitis	-	ROUTINE	ROUTINE	-
Lorlatinib (ALK+ NSCLC)	PO	ALK-rearranged NSCLC with leptomeningeal disease; highest CNS penetration among ALK inhibitors	100 mg :: PO :: daily :: Lorlatinib 100 mg PO daily; alternative: alectinib 600 mg PO BID; intracranial response rates 60-80%	Severe hepatic impairment; concurrent strong CYP3A inducers; hyperlipidemia; CNS effects (mood, cognition)	Lipid panel monthly; LFTs monthly; neuropsychiatric assessment; ECG; CBC	-	ROUTINE	ROUTINE	-
Tucatinib (HER2+ breast)	PO	HER2-positive breast cancer with leptomeningeal disease; small molecule with CNS penetration	300 mg :: PO :: BID :: Tucatinib 300 mg PO BID + trastuzumab (IV per schedule) + capecitabine 1000 mg/m2 PO BID days 1-14 q21d; per HER2CLIMB trial; trastuzumab deruxtecan (T-DXd) 5.4 mg/kg IV q3wk is alternative (DESTINY-Breast03 CNS data)	Severe hepatic impairment; capecitabine: DPD deficiency (fatal toxicity); severe renal impairment	LFTs q2 weeks x 8 weeks then monthly; CBC q3 weeks; hand-foot syndrome monitoring; diarrhea assessment; cardiac function (LVEF q3 months)	-	ROUTINE	ROUTINE	-
Ipilimumab + nivolumab (melanoma)	IV	Melanoma with leptomeningeal disease; immunotherapy combination has best intracranial activity	3 mg/kg + 1 mg/kg :: IV :: q3 weeks x 4 :: Ipilimumab 3 mg/kg + nivolumab 1 mg/kg IV q3 weeks for 4 cycles, then nivolumab 480 mg IV q4 weeks maintenance; BRAF+ melanoma: dabrafenib 150 mg BID + trametinib 2 mg daily is alternative (faster response); response rate for LMD is lower than parenchymal disease	Active autoimmune disease requiring systemic immunosuppression (relative); solid organ transplant; concurrent high-dose steroids (>10 mg prednisone equivalent — reduces immunotherapy efficacy)	irAE monitoring (hepatic, thyroid, adrenal, colitis, pneumonitis, dermatitis); LFTs and TSH before each cycle; glucose; lipase; neurologic exam for immune-related neurotoxicity	-	ROUTINE	ROUTINE	-
High-dose methotrexate (hematologic malignancies)	IV	Lymphomatous or leukemic meningitis; high-dose systemic methotrexate achieves therapeutic CSF levels	3.5 g/m2 :: IV :: per protocol :: High-dose methotrexate 3.5 g/m2 IV over 4h with leucovorin rescue; alternatively, high-dose cytarabine 3 g/m2 IV q12h x 4-6 doses; ibrutinib (for CLL/mantle cell) or lenalidomide (for DLBCL) may have CNS activity; coordinate with hematology/oncology	Renal impairment (creatinine clearance <60); third-space fluid collections; concurrent NSAIDs or PPIs (impair MTX clearance); mucositis	MTX levels q6h until <0.05 mcM; aggressive IV hydration (3 L/m2/day); urine alkalinization (pH >7); renal function; CBC; mucositis	-	URGENT	-	URGENT
VP shunt placement	Surgical	Symptomatic communicating hydrocephalus from LMD not responsive to medical management; persistent elevated ICP despite steroids and diuretics; improves quality of life and enables IT chemotherapy	N/A :: Surgical :: procedure :: Neurosurgical VP shunt placement; programmable valve preferred (allows pressure adjustments); consider Ommaya reservoir placement at same surgery if IT chemo planned; filter may be considered to prevent peritoneal tumor seeding (controversial efficacy)	Active CNS or systemic infection; severe coagulopathy; peritoneal carcinomatosis (relative — use VA or VPL shunt instead); high CSF protein causing frequent shunt obstruction	Post-op CT for catheter position; valve pressure optimization; shunt function assessment; infection surveillance; peritoneal seeding monitoring (theoretical risk)	-	URGENT	ROUTINE	-

3C. Adjunctive/Supportive Treatment¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Levetiracetam (seizure maintenance)	PO/IV	Post-seizure maintenance; cortical irritation from leptomeningeal disease; preferred AED in cancer (no CYP interactions with chemotherapy)	500 mg :: PO :: BID :: Start 500 mg PO/IV BID; titrate to seizure control (max 1500 mg BID); renal dose adjustment if CrCl <50; IV available if NPO	Renal impairment (dose adjust); known hypersensitivity	Seizure recurrence; behavioral changes (irritability, depression); renal function for dose adjustment	-	STAT	ROUTINE	STAT
Dexamethasone taper	PO	Symptom management transition from acute IV to oral; taper as definitive treatment initiated	4 mg :: PO :: q6h taper :: Taper from 16 mg/day: 16 to 12 to 8 to 6 to 4 to 2 to 1 to off, reducing every 3-5 days; slower taper if symptoms recur; minimum effective dose long-term; monitor for adrenal insufficiency if >3 weeks	Inability to taper due to symptoms (consider radiation to enable taper); adrenal suppression after prolonged use	Blood glucose (daily on steroids); weight; mental status (steroid psychosis); proximal weakness (steroid myopathy); cushingoid features; bone density if prolonged	-	ROUTINE	ROUTINE	-
Acetazolamide	PO	Adjunctive ICP reduction; mild communicating hydrocephalus; headache from elevated CSF pressure when surgical CSF diversion not indicated or not yet available	250 mg :: PO :: BID :: Start 250 mg PO BID; may increase to 250 mg TID or 500 mg BID; max 2 g/day; reduces CSF production by 50%	Severe hepatic insufficiency; sulfonamide allergy; severe metabolic acidosis; hyponatremia; hypokalemia	BMP (metabolic acidosis, hypokalemia); renal function; symptoms of ICP (headache, vision); tingling in extremities (common, benign)	-	ROUTINE	ROUTINE	-
Ondansetron	IV/PO	Nausea and vomiting from elevated ICP, chemotherapy, or radiation therapy	4-8 mg :: IV :: q8h PRN :: Ondansetron 4-8 mg IV/PO q8h PRN nausea/vomiting; use around the clock during IT chemotherapy and radiation; dexamethasone itself provides anti-emetic effect	QTc prolongation (check ECG if risk factors); serotonin syndrome with concurrent serotonergic agents; severe hepatic impairment (max 8 mg/day)	QTc if multiple QT-prolonging medications; constipation; headache	STAT	ROUTINE	ROUTINE	STAT
Leucovorin rescue (with IT methotrexate)	PO	Prevents systemic methotrexate toxicity from IT methotrexate absorbed systemically; mandatory with each IT MTX dose	10 mg :: PO :: q6h x 4 doses :: Leucovorin 10 mg PO q6h for 4 doses starting 24 hours after each IT methotrexate administration; increase to 25 mg q6h if elevated serum MTX levels; continue until serum MTX level <0.05 microM	Known hypersensitivity (rare)	Serum methotrexate level at 24h and 48h if concurrent systemic MTX; CBC; mucositis; diarrhea	-	ROUTINE	ROUTINE	-
TMP-SMX (PJP prophylaxis)	PO	Prolonged dexamethasone (>20 mg/week) combined with chemotherapy or immunosuppressive therapy	1 DS tablet :: PO :: 3x/week :: TMP-SMX 1 DS tablet PO Monday/Wednesday/Friday; alternative if sulfa allergic: atovaquone 1500 mg PO daily or dapsone 100 mg PO daily (check G6PD first)	Sulfa allergy; G6PD deficiency (for dapsone alternative); severe renal impairment; megaloblastic anemia from folate deficiency	CBC (leukopenia from TMP-SMX); renal function; rash; GI symptoms	-	ROUTINE	ROUTINE	-
Calcium + Vitamin D	PO	Steroid-induced osteoporosis prevention; expected prolonged steroid course	1000 mg + 800 IU :: PO :: daily :: Calcium 1000-1200 mg/day + Vitamin D3 800-1000 IU/day; divided dosing improves absorption; take with meals	Hypercalcemia; calcium-containing renal stones; sarcoidosis	Serum calcium; 25-OH Vitamin D level; renal function	-	ROUTINE	ROUTINE	-
Acetaminophen (headache/pain)	PO/IV	Headache from elevated ICP or meningeal irritation; first-line analgesic; avoid NSAIDs with concurrent methotrexate	650-1000 mg :: PO :: q6h :: Acetaminophen 650-1000 mg PO q6h; max 4 g/day (2 g/day if hepatic impairment); dexamethasone often most effective for LMD headache; avoid NSAIDs if concurrent methotrexate (impairs clearance) or thrombocytopenia	Hepatic impairment (max 2 g/day); severe hepatic failure	Pain scores q4h; hepatic function if prolonged use	STAT	STAT	ROUTINE	STAT
Gabapentin (neuropathic/radicular pain)	PO	Radicular pain from nerve root involvement (cauda equina); neuropathic pain from cranial neuropathies	300 mg :: PO :: TID :: Start 300 mg PO at bedtime; titrate by 300 mg/day every 3 days to 300-900 mg TID; max 3600 mg/day; renal dose adjustment if CrCl <60	Renal impairment (dose adjust); known hypersensitivity	Sedation; dizziness; peripheral edema; renal function for dose adjustment	-	ROUTINE	ROUTINE	-
Morphine (moderate-severe pain)	IV	Moderate to severe headache or radicular pain not responsive to acetaminophen and gabapentin	2-4 mg :: IV :: q4h PRN :: Morphine 2-4 mg IV q4h PRN severe pain; titrate to pain control; start bowel regimen (docusate 100 mg BID + senna) concurrently; avoid NSAIDs with IT MTX or thrombocytopenia	Respiratory depression; obtundation; severe hepatic impairment; concurrent CNS depressants (dose reduce)	Pain scores q4h; sedation level; respiratory rate (hold if RR <10); constipation; bowel regimen compliance	STAT	STAT	-	STAT
Oxycodone (oral pain management)	PO	Moderate to severe pain for patients tolerating oral medications; transition from IV opioids	5 mg :: PO :: q4-6h PRN :: Oxycodone 5-10 mg PO q4-6h PRN; titrate to pain control; start bowel regimen concurrently; avoid NSAIDs with IT MTX or thrombocytopenia	Respiratory depression; obtundation; severe hepatic impairment; concurrent CNS depressants	Pain scores q4h; sedation level; respiratory status; constipation; bowel regimen compliance	-	ROUTINE	ROUTINE	-
Memantine (with WBRT)	PO	Cognitive neuroprotection during whole-brain radiation therapy	5 mg :: PO :: daily :: Start 5 mg PO daily x 1 week, then 5 mg BID x 1 week, then 10 mg AM + 5 mg PM x 1 week, then 10 mg BID; continue for 6 months total; start day 1 of WBRT	Severe renal impairment (CrCl <5); known hypersensitivity	Cognitive function monitoring; renal function; dizziness; confusion	-	ROUTINE	ROUTINE	-
Insulin (steroid-induced hyperglycemia)	SC/IV	Hyperglycemia management in patients on high-dose dexamethasone; occurs in 50-60% of steroid-treated patients	Per sliding scale :: SC :: q6h :: Fingerstick glucose q6h; sliding scale insulin initially; transition to basal-bolus if persistent >180 mg/dL (typically need 2-3x baseline insulin requirements); glucose peaks 4-8 hours after steroid dose; anticipate insulin needs decrease as steroids taper	Hypoglycemia risk (especially as steroids taper — adjust insulin promptly)	Fingerstick glucose q6h (q1h if insulin drip); HbA1c monthly if prolonged steroids; hypoglycemia symptoms; adjust insulin as steroid dose changes	STAT	STAT	ROUTINE	STAT

3D. Medications to AVOID or Use with Caution¶

Treatment	Route	Indication	Dosing	Pre-Treatment Requirements	Contraindications	Monitoring	ED	HOSP	OPD	ICU
IT chemotherapy with blocked CSF flow	IT	Blocked CSF flow (verified by radionuclide flow study) leads to poor drug distribution and markedly increased neurotoxicity from drug accumulation	Do NOT administer IT chemotherapy until CSF flow study confirms normal flow or radiation clears obstruction	CSF flow study (In-111 DTPA) required before initiating IT chemotherapy	Blocked CSF flow; administer focal radiation to site of block first, then repeat flow study before starting IT chemo	Chemical meningitis; leukoencephalopathy; myelopathy if drug pools at block site	-	-	-	-
Preservative-containing solutions via IT route	IT	Preservatives (benzyl alcohol, methylparaben) are directly neurotoxic when administered intrathecally; can cause fatal chemical arachnoiditis	ALL IT medications must be preservative-free; only preservative-free normal saline for reconstitution	Pharmacy verification of preservative-free status for every IT preparation	ANY preservative-containing solution is ABSOLUTELY CONTRAINDICATED intrathecally	Acute chemical meningitis; seizures; death if preservative administered IT	-	-	-	-
Enzyme-inducing AEDs (phenytoin, carbamazepine, phenobarbital)	PO	CYP enzyme induction reduces efficacy of many chemotherapy agents, targeted therapies, and dexamethasone	Use levetiracetam, lacosamide, or valproic acid instead (non-enzyme-inducing); if already on phenytoin, transition to levetiracetam	Review all drug interactions with oncology team	Concurrent use with temozolomide, irinotecan, many targeted agents; reduce dexamethasone efficacy	Seizure control during transition; AED levels	-	-	-	-
NSAIDs (concurrent with methotrexate)	PO	NSAIDs reduce renal clearance of methotrexate, increasing systemic toxicity risk even with IT administration	Avoid ibuprofen, naproxen, ketorolac while receiving IT or systemic methotrexate; use acetaminophen for pain	Review all medications for MTX interactions	Concurrent IT or systemic methotrexate use; thrombocytopenia	Methotrexate levels; renal function; CBC	-	-	-	-
Lumbar puncture with obstructive hydrocephalus or significant mass effect	-	Risk of transtentorial or tonsillar herniation if LP performed with obstructive hydrocephalus or significant mass effect from concurrent parenchymal metastases	Obtain CT head before LP; if obstructive hydrocephalus present, obtain neurosurgery consult for EVD before LP	CT head demonstrating no obstructive hydrocephalus and no midline shift >5mm	Obstructive hydrocephalus; midline shift >5mm; large posterior fossa mass	Neurologic exam post-LP; immediate imaging if clinical decline	-	-	-	-
High-dose systemic methotrexate concurrent with IT methotrexate	IV/IT	Combined systemic and intrathecal methotrexate increases risk of severe leukoencephalopathy and myelosuppression	Coordinate timing with oncology; do not give IT MTX within 24-48h of systemic MTX without methotrexate level clearance	Serum methotrexate levels must be <0.05 microM before IT dosing	Concurrent elevated serum methotrexate levels	Serum MTX levels; CBC; neurologic exam; MRI for leukoencephalopathy	-	-	-	-

4. OTHER RECOMMENDATIONS¶

4A. Essential¶

Recommendation	ED	HOSP	OPD	ICU	Details
Neurosurgery consultation for Ommaya reservoir placement and possible VP shunt	STAT	STAT	ROUTINE	STAT	Essential for IT chemotherapy delivery; VP shunt if symptomatic hydrocephalus; emergent EVD if acute obstructive hydrocephalus with declining consciousness
Neuro-oncology consultation for treatment planning and coordination	-	URGENT	ROUTINE	URGENT	LMD management requires subspecialty neuro-oncology input; treatment selection (IT chemo vs. systemic vs. radiation); clinical trial eligibility; prognosis discussion
Radiation oncology consultation for involved-field RT, WBRT, or craniospinal irradiation	-	URGENT	ROUTINE	-	Radiation to symptomatic sites, CSF flow blocks, and diffuse leptomeningeal disease; coordinate with IT chemotherapy schedule
Medical oncology consultation for systemic therapy with CNS penetration	-	URGENT	ROUTINE	-	Molecular profiling results guide targeted therapy selection (osimertinib, tucatinib, immunotherapy); systemic disease management; clinical trial evaluation
Multidisciplinary tumor board review	-	URGENT	ROUTINE	-	LMD requires coordinated input from neuro-oncology, radiation oncology, medical oncology, neurosurgery, and neuroradiology; optimal treatment sequencing critical
Goals of care and prognosis discussion with patient and family	-	URGENT	ROUTINE	URGENT	Median survival 2-4 months for solid tumors (longer with targeted therapy); discuss treatment intent (palliative vs. life-prolonging); code status; advance directives; hospice eligibility; involve palliative care early
Palliative care consultation for symptom management and goals of care facilitation	-	URGENT	ROUTINE	URGENT	Early palliative care integration improves quality of life and may improve survival; symptom management (pain, nausea, headache); psychosocial support; advance care planning
Fall precautions and safety measures	STAT	STAT	ROUTINE	STAT	LMD patients at high fall risk (cranial neuropathies causing visual impairment, lower extremity weakness from cauda equina involvement, ataxia, cognitive impairment, steroid myopathy); bed alarm; walker evaluation; remove fall hazards

4B. Patient Instructions¶

Recommendation	ED	HOSP	OPD	ICU	Details
Speech-language pathology evaluation	-	ROUTINE	ROUTINE	-	If dysphagia from cranial neuropathies (CN IX, X, XII involvement); dysarthria assessment; modified barium swallow study if aspiration suspected
Physical therapy and occupational therapy	-	ROUTINE	ROUTINE	-	Functional assessment; mobility training for lower extremity weakness (cauda equina); ADL adaptation; energy conservation; home safety evaluation
Neuropsychology evaluation	-	-	ROUTINE	-	Baseline cognitive assessment before radiation; monitor cognitive decline; guide rehabilitation and support services
Social work and case management	-	ROUTINE	ROUTINE	-	Insurance authorization for IT chemotherapy, radiation, targeted agents; home care coordination; caregiver support; disability paperwork; hospice referral when appropriate
Clinical trials evaluation	-	ROUTINE	ROUTINE	-	Active LMD trials (novel IT agents, systemic agents, intrathecal antibodies); NCI clinical trials database; institutional trials; LMD-specific trials expanding
Pain management consultation	-	ROUTINE	ROUTINE	-	Refractory headache or radicular pain not responsive to standard analgesics and steroids; neuropathic pain management; opioid optimization
Ophthalmology consultation	-	ROUTINE	ROUTINE	-	Visual complaints from cranial neuropathies (CN II, III, IV, VI involvement); papilledema assessment; formal visual fields; fundoscopic examination
Driving restriction counseling	-	ROUTINE	ROUTINE	-	Advise against driving if cranial neuropathies affecting vision, seizures, cognitive impairment, or significant lower extremity weakness; state-specific reporting requirements

4C. Lifestyle & Prevention¶

Recommendation	ED	HOSP	OPD	ICU	Details
CSF flow study before IT chemotherapy initiation	-	ROUTINE	ROUTINE	-	Radionuclide CSF flow study (In-111 DTPA) to identify CSF flow obstruction; 30-70% of LMD patients have abnormal flow; blocked flow requires focal radiation before IT chemotherapy (drug pools at obstruction site causing neurotoxicity)
Endoscopic third ventriculostomy (ETV)	-	ROUTINE	-	-	Alternative to VP shunt for obstructive hydrocephalus from LMD at aqueduct or fourth ventricle outlet; avoids hardware-related complications; may not be feasible if leptomeningeal tumor involvement at floor of third ventricle
Hospice referral	-	ROUTINE	ROUTINE	-	KPS <40; progressive disease despite treatment; no further treatment options; patient/family preference for comfort-focused care; median survival for refractory LMD is weeks; ensure adequate symptom control transition
Re-biopsy or CSF sampling for molecular evolution	-	ROUTINE	ROUTINE	-	CSF cfDNA or repeat cytology at progression to identify new actionable mutations (clonal evolution); treatment-resistant clones may have different molecular profile than primary tumor

═══════════════════════════════════════════════════════════════ SECTION B: SUPPORTING INFORMATION ═══════════════════════════════════════════════════════════════

5. DIFFERENTIAL DIAGNOSIS¶

Primary Differential Diagnoses¶

Diagnosis	Key Differentiating Features	Distinguishing Studies
Bacterial meningitis	Acute onset; high fever; nuchal rigidity; toxic appearance; CSF with neutrophilic pleocytosis, very low glucose, very high protein, positive Gram stain; rapid deterioration; no history of malignancy typically	CSF Gram stain and culture (positive); CSF WBC typically >1000 with neutrophil predominance; blood cultures; procalcitonin; CRP markedly elevated; rapid clinical response to antibiotics
Tuberculous meningitis	Subacute onset (days to weeks); basilar meningitis on MRI; cranial neuropathies (similar to LMD); CSF lymphocytic pleocytosis, low glucose, high protein; endemic exposure; immunocompromised	CSF AFB smear and culture (low sensitivity ~10-30%); CSF adenosine deaminase (ADA >10 U/L); TB PCR (GeneXpert); chest X-ray (miliary pattern); TST/IGRA; basal cistern enhancement pattern on MRI
Fungal meningitis (cryptococcal, coccidioidal)	Immunocompromised host (HIV, transplant); subacute headache and confusion; elevated ICP; basilar meningitis; cranial neuropathies possible	CSF cryptococcal antigen (high sensitivity); CSF fungal culture; serum cryptococcal antigen; CSF India ink (low sensitivity); Coccidioides CF antibody; CSF opening pressure often very high
Neurosarcoidosis	Leptomeningeal enhancement on MRI (can mimic LMD); cranial neuropathies (especially CN VII); young adults; no malignancy history; systemic sarcoidosis features (hilar lymphadenopathy, skin, eyes)	Chest CT (hilar lymphadenopathy); serum ACE (low sensitivity); CSF lymphocytic pleocytosis, elevated protein; gallium or PET scan; tissue biopsy showing non-caseating granulomas; no malignant cells on CSF cytology
CNS vasculitis	Multifocal neurologic deficits; headache; cognitive decline; leptomeningeal enhancement possible; beading/irregularity of cerebral vessels on angiography	MR angiography or conventional angiography (vessel beading); CSF lymphocytic pleocytosis, elevated protein; ESR/CRP elevated; leptomeningeal/brain biopsy; ANA, ANCA, complement levels
Primary CNS lymphoma (PCNSL)	Periventricular enhancing lesions; may have secondary leptomeningeal involvement; immunocompromised patients; dramatic response to corticosteroids ("ghost tumor"); CSF cytology or flow cytometry shows clonal lymphocytes	CSF flow cytometry (clonal B-cells); MRI pattern (periventricular, homogeneous enhancement); biopsy (DO NOT give steroids before biopsy if possible); slit-lamp exam for vitreous involvement; HIV test
Viral meningitis/encephalitis	Acute onset; fever; headache; photophobia; CSF lymphocytic pleocytosis with normal glucose; self-limited (most viral causes); no malignancy history	CSF viral PCR panel (HSV, VZV, enterovirus); CSF cell count (lymphocytic but typically less elevated than bacterial); normal or mildly elevated protein; normal glucose (unlike LMD); clinical improvement over days
Autoimmune/paraneoplastic encephalitis	Subacute cognitive decline, seizures, psychiatric symptoms; may have leptomeningeal enhancement; can coexist with or be triggered by underlying malignancy	Paraneoplastic antibody panel (serum and CSF); CSF: mild pleocytosis, elevated protein, oligoclonal bands; MRI: limbic/temporal signal changes; EEG abnormalities; whole-body PET to identify occult malignancy
Chemical meningitis (post-procedure)	History of recent neurosurgical procedure, LP, IT chemotherapy, or myelography; headache, fever, neck stiffness; CSF: neutrophilic pleocytosis but sterile cultures	Temporal relationship to procedure (onset within hours to days); CSF cultures negative (critical distinction); CSF glucose usually normal or mildly reduced; self-resolving; dexamethasone responsive
Dural metastases without leptomeningeal involvement	Dura-based enhancing lesions on MRI; may mimic meningioma; mass effect; breast and prostate cancer most common dural metastases; CSF cytology negative	MRI: dural-based enhancement (pachymeningeal) rather than pial/leptomeningeal; CT may show bone involvement; CSF cytology typically negative; biopsy for tissue diagnosis if needed

Red Flags Requiring Urgent Reassessment¶

Red Flag	Concern	Action
Rapid decline in consciousness (GCS drop >2 points)	Acute hydrocephalus; herniation; hemorrhage into tumor	STAT CT head; neurosurgery STAT for EVD if hydrocephalus; escalate to ICU
New bilateral leg weakness or urinary retention	Cauda equina syndrome from LMD; spinal cord compression	STAT MRI whole spine; dexamethasone 10 mg IV; neurosurgery and radiation oncology STAT
Acute visual loss	Optic nerve involvement from LMD; papilledema from elevated ICP; pituitary metastasis	STAT ophthalmology; CT head (hydrocephalus); MRI brain with orbital cuts; consider emergent LP for ICP if safe
New cranial neuropathies (facial weakness, diplopia, hearing loss, dysphagia)	Progressive LMD; treatment failure; may require change in therapy or urgent radiation	MRI brain with thin cuts through cranial nerves; reassess treatment plan; consider involved-field radiation to affected cranial nerves
Fever after IT chemotherapy	Chemical meningitis (common) vs. Ommaya reservoir infection (dangerous); bacterial meningitis from immunosuppression	Blood cultures; CSF sampling from Ommaya (cell count, Gram stain, culture); if unable to distinguish, empiric antibiotics until cultures finalize; chemical meningitis typically self-limited (24-72h)
Status epilepticus	Cortical irritation from LMD; metabolic derangement; concurrent parenchymal disease	Benzodiazepines STAT; levetiracetam load; CT head; correct metabolic abnormalities; continuous EEG; see Status Epilepticus template
Severe headache with Cushing triad (hypertension, bradycardia, irregular respirations)	Impending herniation from acute hydrocephalus or massive leptomeningeal tumor burden	STAT CT; neurosurgery for emergent EVD; mannitol or hypertonic saline; intubation if GCS <=8; ICU transfer

6. MONITORING PARAMETERS¶

Acute Phase Monitoring (First 72h)¶

Parameter	Frequency	Target/Threshold	Action if Abnormal	ED	HOSP	OPD	ICU
Neurologic checks (GCS, cranial nerves, motor, sensory)	q1-2h in ICU; q2-4h on floor	Stable or improving exam; no new cranial neuropathies	STAT CT if decline; neurosurgery for EVD if hydrocephalus; consider dexamethasone increase or emergent radiation	STAT	STAT	-	STAT
Blood glucose	q6h (q1h if insulin drip)	140-180 mg/dL	Sliding scale to basal-bolus insulin; typically need 2-3x baseline insulin on dexamethasone; adjust as steroids taper	STAT	STAT	-	STAT
Blood pressure	Continuous in ICU; q4h on floor	SBP <160; avoid hypotension (SBP >100 for cerebral perfusion)	Antihypertensives PRN; avoid agents that mask neurologic changes	STAT	STAT	-	STAT
Sodium	q6-8h initially	135-145 mEq/L	Hyponatremia (SIADH common with CNS malignancy): fluid restrict if mild; 3% NaCl if <125 or symptomatic; correct no faster than 8 mEq/L per 24h	STAT	STAT	-	STAT
Pain assessment	q4h	NRS <4/10	Escalate analgesics; dexamethasone most effective for LMD headache; consider opioids for moderate-severe; avoid NSAIDs with methotrexate	STAT	STAT	-	STAT
Seizure monitoring	Continuous observation; consider cEEG if AMS	No clinical or subclinical seizures	Levetiracetam load if first seizure; dose optimization; continuous EEG for unexplained encephalopathy	STAT	STAT	-	STAT
ICP monitoring (if EVD in place)	Continuous	ICP <20 mmHg; CPP >60 mmHg	CSF drainage; osmotherapy; elevate HOB 30 degrees; consider decompressive procedure if refractory	-	-	-	STAT

Subacute and Outpatient Monitoring¶

Parameter	Frequency	Target/Threshold	Action if Abnormal	ED	HOSP	OPD	ICU
MRI brain and spine with contrast	q6-8 weeks during active treatment; q3 months during maintenance	Stable or improving leptomeningeal enhancement; no new disease; resolution of cranial nerve enhancement	Progressive enhancement: change IT agent, add systemic therapy, add radiation; new disease: reassess treatment plan at tumor board	-	ROUTINE	ROUTINE	-
CSF cytology (serial)	With each IT chemo cycle; q4-8 weeks	Cytology conversion to negative (CSF clearance)	Persistent positive cytology after 4-6 weeks of IT chemo: switch IT agent; add systemic therapy; consider radiation	-	ROUTINE	ROUTINE	-
CBC	Before each IT chemo cycle; weekly during induction	ANC >1500; platelets >50,000 (for LP/IT chemo)	Hold IT chemo if ANC <1500 or platelets <50,000; growth factor support if needed; dose reduction	-	ROUTINE	ROUTINE	-
Renal function (BMP)	Before each IT methotrexate; monthly during systemic therapy	Creatinine clearance >60 for MTX; normal electrolytes	Dose adjust or hold methotrexate; hydration; nephrology if declining	-	ROUTINE	ROUTINE	-
Hepatic function (LFTs)	Monthly during systemic targeted therapy	Normal ALT/AST (<3x ULN); normal bilirubin	Hold targeted therapy if ALT/AST >5x ULN; dose reduce per drug-specific guidelines; hepatology if persistent	-	ROUTINE	ROUTINE	-
Neurologic examination	Each clinic visit (q1-2 weeks during treatment, q2-4 weeks maintenance)	Stable or improved cranial nerve function; stable gait; preserved cognition	New deficits: urgent MRI; reassess treatment response; consider radiation to progressive sites	-	ROUTINE	ROUTINE	-
KPS / ECOG performance status	Each visit	KPS >=60 for active treatment; KPS >=40 for palliative IT chemo	KPS <40: transition to comfort-focused care; hospice referral; discontinue aggressive treatment	-	ROUTINE	ROUTINE	-
Steroid taper progress	Each visit	Minimum effective dose or off steroids	Steroid-dependent symptoms: consider radiation or bevacizumab to enable taper; manage steroid complications	-	ROUTINE	ROUTINE	-
Depression/anxiety screening (PHQ-9)	Each visit	PHQ-9 <5	SSRI (sertraline, escitalopram — low CYP interaction); psychology referral; supportive care; palliative care involvement	-	ROUTINE	ROUTINE	-
Ommaya reservoir site assessment	Each access (q1-2 weeks during IT chemo)	No erythema, warmth, tenderness, swelling, or CSF leak	Suspect infection: aspirate CSF from Ommaya for culture; CT head; empiric antibiotics (vancomycin + cefepime) until culture results; reservoir removal if confirmed infection	-	ROUTINE	ROUTINE	-

7. DISPOSITION CRITERIA¶

Admission Criteria¶

Level of Care	Criteria
ICU admission	GCS <=12; signs of herniation (pupil asymmetry, posturing, Cushing triad); acute obstructive hydrocephalus requiring emergent EVD; status epilepticus; respiratory failure from brainstem involvement or neuromuscular weakness; hemodynamic instability; post-Ommaya or VP shunt placement (first 12-24h per institutional protocol)
General neurology/neurosurgery floor	New diagnosis of LMD requiring workup and treatment initiation; symptomatic hydrocephalus requiring monitoring; initiation of IT chemotherapy (first 1-2 doses for monitoring); post-Ommaya placement (step-down from PACU/ICU); post-seizure requiring AED optimization; rapidly progressive neurologic deficits; severe headache/nausea requiring IV management
Observation (<=24h)	Known LMD with mild symptom change; steroid dose adjustment with monitoring; planned same-day IT chemotherapy via established Ommaya with adequate observation

Discharge Criteria¶

Criterion	Details
Neurologic stability	Stable or improving neurologic exam for >=24h; no new cranial neuropathies; no worsening headache or confusion
Hydrocephalus management	If hydrocephalus present: VP shunt functioning; symptoms controlled; no evidence of shunt malfunction
IT chemotherapy plan	IT chemo schedule established; Ommaya functioning if placed; patient and family educated on reservoir care; outpatient IT chemo arrangements confirmed
Seizure control	Seizure-free >=24h on oral AED; therapeutic dosing of levetiracetam established
Pain control	Headache and pain adequately managed on oral medications
Steroid plan	Oral dexamethasone regimen with clear taper schedule; glucose management plan (insulin if needed); PPI prescribed
Functional safety	Safe ambulation (with or without assistive device); safe swallowing; adequate home support or home health arranged
Follow-up arranged	Neuro-oncology (1-2 weeks); radiation oncology (if RT planned, within 1 week); medical oncology (1-2 weeks for systemic therapy); neurosurgery (2 weeks if post-Ommaya or VP shunt); PCP (1 week for steroid monitoring); MRI brain/spine scheduled at 6-8 weeks
Patient/family education	Understanding of diagnosis and prognosis; IT chemo schedule and what to expect; signs requiring ED return (acute headache, fever, new weakness, seizure, vision changes, altered consciousness, signs of Ommaya infection); advance care planning discussed; palliative care follow-up if indicated
Goals of care documented	Code status documented; advance directive discussed; palliative care involvement if appropriate; hospice referral if prognosis very poor and patient/family prefer comfort care

Discharge Prescriptions Checklist¶

Medication	Details
Dexamethasone	Dose and taper schedule clearly documented; lowest effective dose
PPI	Omeprazole 20 mg daily or pantoprazole 40 mg daily while on steroids
Levetiracetam	If seizure occurred; dose and frequency documented; DO NOT start if no seizure history
Insulin (if needed)	Sliding scale or basal-bolus for steroid-induced hyperglycemia; glucometer and supplies; education on adjustment as steroids taper
Leucovorin	10 mg PO q6h x 4 doses starting 24h after each IT methotrexate dose (if on IT MTX)
PJP prophylaxis	TMP-SMX if on high-dose steroids + chemotherapy
Calcium + Vitamin D	If steroids >2 weeks anticipated
Analgesics	Acetaminophen, gabapentin for neuropathic pain, limited opioid if needed
Anti-emetics	Ondansetron 4-8 mg q8h PRN
Stool softener	Docusate 100 mg BID if on opioids

8. EVIDENCE & REFERENCES¶

Key Guidelines¶

Guideline	Source	Year	Key Recommendation
Leptomeningeal Metastases	NCCN Central Nervous System Cancers	v1.2025	Diagnosis via CSF cytology, flow cytometry, and/or MRI; IT chemotherapy (methotrexate, cytarabine) or systemic CNS-penetrant therapy; radiation for symptomatic sites; supportive care and palliative care integration
EANO-ESMO Guidelines on Leptomeningeal Metastases	Le Rhun et al. Ann Oncol 2017	2017	Type I (positive CSF cytology) vs. Type II (MRI only) classification; CSF flow study before IT chemo; involved-field RT for symptomatic bulky disease; systemic therapy preferred for certain primaries (EGFR+ NSCLC, HER2+ breast)
RANO Leptomeningeal Metastases Group Proposal	Chamberlain et al. Neuro Oncol 2017	2017	Standardized response criteria for LMD clinical trials; CSF cytology, MRI, and clinical neurologic exam as response measures

Landmark Studies¶

Study	Finding	Impact
Grossman et al. J Clin Oncol 1993	IT methotrexate vs. IT thiotepa for LMD: no significant difference in survival; overall median survival 15.9 weeks with IT chemo	Established IT methotrexate and thiotepa as equivalent first-line IT agents; demonstrated modest benefit of IT chemotherapy
Glantz et al. J Clin Oncol 1999	Liposomal cytarabine (DepoCyt) vs. methotrexate for LMD: liposomal cytarabine had longer time to neurologic progression (58 vs. 30 days) and higher cytologic response; less frequent dosing schedule	Established liposomal cytarabine as alternative to methotrexate with more convenient dosing; demonstrated importance of cytologic response
Boogerd et al. Neurology 2004	IT chemotherapy added to RT did not improve survival vs. RT alone in breast cancer LMD	Questioned benefit of IT chemotherapy over radiation alone; highlighted need for better agents and patient selection
Shapiro et al. J Neurooncol 2006	CSF flow study results predict response to IT chemotherapy: abnormal flow associated with poorer response and increased toxicity	Established CSF flow study as required pre-treatment evaluation before IT chemotherapy
Yang et al. J Clin Oncol 2020 (BLOOM)	Osimertinib 160 mg daily for EGFR+ NSCLC LMD: response rate 62%; median PFS 8.6 months; CSF concentration therapeutic	Established osimertinib as preferred systemic agent for EGFR+ NSCLC with LMD; may replace IT chemotherapy for this population
Murthy et al. N Engl J Med 2020 (HER2CLIMB)	Tucatinib + trastuzumab + capecitabine: intracranial response 47%; CNS-PFS 9.9 vs. 4.2 months; includes patients with LMD	Established tucatinib combination for HER2+ breast cancer with brain/leptomeningeal metastases
Tawbi et al. N Engl J Med 2018 (CheckMate 204)	Ipilimumab + nivolumab in melanoma brain metastases: intracranial response 57% in asymptomatic; LMD cohort response lower but activity demonstrated	Established combination immunotherapy for melanoma CNS disease; some activity in LMD cohort
Le Rhun et al. Neuro Oncol 2020	CSF cell-free DNA (cfDNA) for LMD diagnosis: sensitivity 81% vs. 67% for cytology; can identify actionable mutations and monitor treatment response	Emerging role for CSF liquid biopsy in LMD diagnosis and molecular profiling; may supplement or replace cytology
Pan et al. Lancet Oncol 2016	CSF flow abnormalities in LMD: 30-70% of patients have blocked flow; focal radiation can restore flow in majority; improved IT chemotherapy efficacy after flow restoration	Reinforced importance of pre-treatment CSF flow evaluation; established radiation for flow restoration
Brown et al. JAMA Oncol 2020 (NRG-CC001)	HA-WBRT + memantine superior to standard WBRT + memantine for cognitive preservation at 4 and 6 months	HA-WBRT + memantine = new standard when WBRT indicated (applicable to LMD patients requiring WBRT)

Prognosis References¶

Study	Finding	Impact
Brower et al. Neuro Oncol Pract 2016	Systematic review of LMD prognosis: untreated median survival 4-6 weeks; with treatment median survival 2-4 months; breast cancer LMD has best prognosis among solid tumors (4-6 months); NSCLC and melanoma LMD have shorter survival	Key prognostic reference; guides goals of care discussions; identifies patient subgroups with better prognosis
Nayar et al. Neurology 2017	LMD prognostic factors: good KPS (>=70), single cranial nerve deficit, absence of encephalopathy, CSF cytology conversion to negative, and actionable molecular targets associated with longer survival	Identifies patients most likely to benefit from aggressive treatment vs. those better served by comfort care

Grading Scales¶

Leptomeningeal Carcinomatosis Prognostic Score

Factor	Good Prognosis	Poor Prognosis
KPS at diagnosis	>=70	<50
Primary tumor type	Breast cancer (HR+ or HER2+)	Melanoma, NSCLC without driver mutation
Actionable molecular target	Present (EGFR, ALK, HER2)	Absent
Number of cranial neuropathies	0-1	>=3
Encephalopathy at diagnosis	Absent	Present
Systemic disease status	Controlled	Uncontrolled/progressive
CSF flow	Normal	Blocked

Median Survival by Primary Tumor and Treatment

Primary Tumor	Untreated	With IT Chemo	With Targeted Systemic	Notes
Breast (HER2+)	4-6 weeks	4-6 months	8-12 months (tucatinib)	Best prognosis among solid tumors
Breast (HR+/HER2-)	4-6 weeks	3-5 months	4-6 months	Consider abemaciclib (limited CNS data)
Breast (triple-negative)	4-6 weeks	2-3 months	2-4 months	Limited systemic options
NSCLC (EGFR+)	4-6 weeks	3-4 months	8-11 months (osimertinib)	Systemic therapy may be preferred over IT chemo
NSCLC (ALK+)	4-6 weeks	3-4 months	6-10 months (lorlatinib)	Systemic therapy preferred
NSCLC (no driver)	4-6 weeks	2-3 months	2-4 months (immunotherapy)	Limited options; consider clinical trials
Melanoma (BRAF+)	4-6 weeks	2-3 months	4-7 months (combined targeted + immuno)	Immunotherapy may have durable responses
Melanoma (BRAF wild-type)	4-6 weeks	2-3 months	3-5 months (immunotherapy)	Ipilimumab + nivolumab best option
Lymphoma/leukemia	4-6 weeks	4-12 months	Variable	High-dose systemic MTX often effective; best overall prognosis

Karnofsky Performance Status (KPS)

Score	Description
100	Normal, no complaints
90	Able to carry on normal activity; minor signs/symptoms
80	Normal activity with effort; some signs/symptoms
70	Cares for self; unable to carry on normal activity or active work
60	Requires occasional assistance but cares for most needs
50	Requires considerable assistance and frequent medical care
40	Disabled; requires special care and assistance
30	Severely disabled; hospitalization indicated, death not imminent
20	Very sick; active supportive treatment needed
10	Moribund

CHANGE LOG¶

v1.1 (January 30, 2026) - Standardized ALL treatment table dosing fields to structured [dose] :: [route] :: [frequency] :: [full_instructions] format across sections 3A, 3B, 3C - Split bundled seizure management row (3A) into separate Lorazepam and Levetiracetam rows - Split bundled DVT prophylaxis row (3A) into separate Enoxaparin and Heparin rows - Split bundled pain management row (3C) into separate Acetaminophen, Gabapentin, Morphine, and Oxycodone rows - Renamed "Stress ulcer prophylaxis" to "Omeprazole" for specificity - Renamed "PJP prophylaxis" to "TMP-SMX (PJP prophylaxis)" for specificity - Renamed "Glucose management" to "Insulin (steroid-induced hyperglycemia)" for specificity - Renamed systemic therapy entries with drug names (Osimertinib, Lorlatinib, Tucatinib, Ipilimumab + nivolumab, High-dose methotrexate) for clarity - Added surgical procedure dosing format (N/A :: Surgical :: procedure) for EVD, Ommaya, and VP shunt entries - Removed cross-references in IT methotrexate (via LP) row — now self-contained contraindications and monitoring - Renamed Section 4B from "Extended" to "Patient Instructions" per standard template - Renamed Section 4C from "Atypical/Refractory" to "Lifestyle & Prevention" per standard template - Added REVISED date to metadata header - Bumped version from 1.0 to 1.1

v1.0 (January 30, 2026) - Initial template creation - Comprehensive 8-section format with all subsections - Full treatment coverage: IT chemotherapy (methotrexate, cytarabine, thiotepa), systemic targeted therapy (osimertinib, tucatinib, lorlatinib, immunotherapy), radiation (involved-field, WBRT, CSI) - Detailed CSF diagnostic workup including cytology, flow cytometry, cfDNA - Ommaya reservoir and VP shunt management - Hydrocephalus management (acute and chronic) - Prognostic tables by primary tumor type - Palliative care integration throughout - PubMed citations for all landmark studies

APPENDIX A: Treatment Algorithm — Decision Framework¶

LEPTOMENINGEAL CARCINOMATOSIS SUSPECTED
         |
         +-- Acute presentation (obtunded, herniation signs, acute hydrocephalus)?
         |         YES --> Dexamethasone 10 mg IV --> CT head STAT
         |                   |
         |                   +-- Obstructive hydrocephalus? --> Neurosurgery STAT for EVD
         |                   +-- Mass effect/herniation? --> Osmotherapy + ICU
         |                   +-- Stable? --> Proceed to diagnosis below
         |         NO --> Proceed to diagnosis
         |
         +-- Confirm Diagnosis
         |         |
         |         +-- MRI brain + spine with gadolinium (leptomeningeal enhancement?)
         |         +-- Lumbar puncture (CSF cytology, flow cytometry, protein, glucose)
         |         |         |
         |         |         +-- Cytology POSITIVE --> Confirmed LMD (Type I)
         |         |         +-- Cytology NEGATIVE but MRI positive --> Probable LMD (Type II)
         |         |         |         --> Repeat LP in 1-2 weeks (sensitivity improves to ~80%)
         |         |         |         --> Consider CSF cfDNA (sensitivity ~80-90%)
         |         |         +-- Both NEGATIVE --> Alternative diagnosis? Repeat in 2-4 weeks
         |         |
         |         +-- Molecular profiling (primary tumor + CSF if possible)
         |                   |
         |                   +-- Actionable target? (EGFR, ALK, HER2, BRAF)
         |                   +-- Hematologic malignancy? (lymphoma, leukemia)
         |
         +-- Treatment Selection
         |         |
         |         +-- Actionable molecular target present?
         |         |         YES --> Systemic targeted therapy FIRST
         |         |                   +-- EGFR+ NSCLC --> Osimertinib 80-160 mg daily
         |         |                   +-- ALK+ NSCLC --> Lorlatinib 100 mg daily
         |         |                   +-- HER2+ breast --> Tucatinib + trastuzumab + capecitabine
         |         |                   +-- BRAF+ melanoma --> Dabrafenib/trametinib +/- immunotherapy
         |         |                   +-- Melanoma (any) --> Ipilimumab + nivolumab
         |         |                   +-- May still add IT chemo or radiation for symptomatic sites
         |         |         NO --> IT chemotherapy +/- radiation
         |         |
         |         +-- CSF flow study (In-111 DTPA) BEFORE IT chemotherapy
         |         |         |
         |         |         +-- Normal flow --> Proceed with IT chemo
         |         |         +-- Blocked flow --> Focal radiation to block site
         |         |                   --> Repeat flow study --> If restored, start IT chemo
         |         |
         |         +-- IT Chemotherapy regimen
         |         |         +-- First-line: IT methotrexate 12 mg (via Ommaya preferred)
         |         |         +-- Alternative: IT liposomal cytarabine 50 mg q2wk
         |         |         +-- Third-line: IT thiotepa 10 mg
         |         |
         |         +-- Radiation therapy (concurrent or sequential)
         |         |         +-- Symptomatic bulky disease --> Involved-field RT (30 Gy/10 fx)
         |         |         +-- Diffuse cerebral disease --> WBRT (30 Gy/10 fx) + memantine
         |         |         +-- Extensive craniospinal --> CSI (30-36 Gy) if good KPS
         |         |
         |         +-- Hematologic malignancy?
         |                   +-- High-dose systemic MTX (3.5 g/m2) achieves CSF levels
         |                   +-- IT MTX or cytarabine as adjunct
         |                   +-- Disease-specific systemic agents (ibrutinib, lenalidomide)
         |
         +-- Supportive Care (ALL PATIENTS)
         |         +-- Dexamethasone (taper to minimum effective dose)
         |         +-- PPI (stress ulcer prophylaxis)
         |         +-- Glucose management (steroid-induced)
         |         +-- Pain management (headache, radicular)
         |         +-- Seizure management (if seizures occur, no prophylaxis)
         |         +-- DVT prophylaxis
         |         +-- PJP prophylaxis (if prolonged steroids + chemo)
         |         +-- Goals of care discussion + palliative care
         |
         +-- Monitoring
         |         +-- MRI brain/spine q6-8 weeks during treatment
         |         +-- Serial CSF cytology with each IT chemo cycle
         |         +-- Neurologic exam at each visit
         |         +-- KPS assessment (KPS <40 --> transition to comfort care)
         |
         +-- Disease Progression
                   +-- CSF cytology remains positive after 4-6 weeks --> Switch IT agent
                   +-- New symptoms/MRI progression --> Re-evaluate at tumor board
                   +-- CSF molecular profiling for clonal evolution
                   +-- Clinical trials
                   +-- Hospice referral if exhausted options / declining function

APPENDIX B: Ommaya Reservoir Management¶

Pre-Access Checklist¶

Step	Details
Verify reservoir patency	Palpate for subcutaneous dome; assess for erythema, warmth, tenderness
Sterile preparation	Strict aseptic technique; shave site if needed; chlorhexidine or povidone-iodine prep
Butterfly needle	25-gauge butterfly needle; attach to syringe; insert perpendicular through dome
Aspirate CSF	Withdraw 3-5 mL CSF (send for cytology, cell count, protein, culture if indicated)
Inject medication	Inject IT chemotherapy slowly (over 2-3 minutes) in preservative-free saline
Flush	Flush with 2-3 mL preservative-free normal saline
Post-procedure	Patient lies flat for 15-30 min; monitor for 1-2 hours; assess for headache, nausea

Complications of Ommaya Reservoir¶

Complication	Frequency	Management
Infection (bacterial)	5-10%	CSF cultures from reservoir; empiric vancomycin + cefepime; if confirmed, reservoir removal usually required
Malposition/migration	3-5%	CT head to confirm catheter tip position; neurosurgery for revision if malpositioned
Hemorrhage (at insertion)	1-3%	Post-op CT; neurosurgical management if symptomatic
CSF leak	1-3%	Pressure dressing; head elevation; neurosurgery if persistent
Chemical meningitis (from IT chemo)	20-40%	Dexamethasone prophylaxis (especially with liposomal cytarabine); supportive care; self-limited 24-72h
Leukoencephalopathy	5-15% (cumulative)	MRI surveillance; dose reduction or discontinuation of IT chemo; steroids; no specific treatment
Catheter obstruction	5-10%	Unable to aspirate CSF; CT to check position; reservoir tap under fluoroscopy; may need revision

APPENDIX C: CSF Diagnostic Sensitivity Comparison¶

Diagnostic Test	Sensitivity (single sample)	Sensitivity (repeat/combined)	Specificity	Notes
CSF cytology	~50%	~80-90% (2-3 samples)	~100% (if malignant cells identified)	Gold standard; must process within 30 min; large volume improves yield (>10 mL)
CSF flow cytometry	~75-90% (hematologic malignancies)	~95%	~95-100%	Best for lymphoma/leukemia; identifies clonal populations; less useful for solid tumors
CSF cell-free DNA (cfDNA)	~80-90%	N/A	~95-100%	Emerging; can identify mutations; monitor treatment response; may detect LMD before cytology positive
MRI (gadolinium-enhanced)	~70-80%	~85% (with 3D FLAIR)	~85-90%	False positives from infection, inflammation, prior procedures; sensitivity depends on technique
CSF protein elevation	~80% (>50 mg/dL)	N/A	~50% (nonspecific)	Supportive finding only; not diagnostic alone
CSF glucose depression	~40-60%	N/A	~70% (nonspecific)	Suggestive but seen in infection also
CSF tumor markers	~60-80% (varies by marker)	N/A	~80-90%	Best when correlated with serum; CSF:serum ratio >1 suggests intrathecal production

This template represents the initial build phase and requires validation through the checker pipeline (Checker, Rebuilder, Citation Verifier, CPT/Synonym Enricher) before clinical deployment.