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
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
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
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
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)
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
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
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
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
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%
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
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
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)
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
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
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
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
CYP enzyme induction reduces efficacy of many chemotherapy agents, targeted therapies, and dexamethasone
N/A :: PO :: per protocol :: 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
N/A :: PO :: per protocol :: 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
N/A :: - :: once :: 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
N/A :: IV/IT :: per protocol :: 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
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
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
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
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
═══════════════════════════════════════════════════════════════
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
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
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
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
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
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
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)
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
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
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
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
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
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.