OpenOnco · Treatment Plan

Treatment plan — Lymphangioleiomyomatosis

PLAN-BMA-TSC1_LAM-V1 · v1 · 2026-08-18

Patient

BMA-TSC1_LAM · Algorithm: ALGO-LAM-1L

DiagnosisLymphangioleiomyomatosis

MOH / ICD-10J84.81

ICD-O-38894/1; C34

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks

Biomarker	Variant	ESCAT	Evidence	Clinical significance	Drugs	Sources
ESCAT: clinical review pendingBIO-TSC1	TSC1 or TSC2 loss-of-function (LAM context — somatic in sporadic LAM, germline in TSC-associated LAM); mTORC1 hyperactivation is the therapeutic target regardless of TSC1 vs TSC2 specificity	IA	Standard care SRC-MILES-MCCORMACK-2011: Level A (Supports, Sensitivity/Response)	Sirolimus (rapamycin), an mTORC1 inhibitor, is FDA-approved (May 2015) and EMA-approved (2017) for treatment of LAM in adults. MILES phase III RCT (McCormack et al., NEJM 2011): N=89 (46 sirolimus, 43 placebo); 12-month treatment + 12-month observation. Primary endpoint: FEV1 change from baseline to 12 months (mL/month rate). FEV1 slope: +1 mL/month (sirolimus) vs -12 mL/month (placebo); difference 11 mL/month (p<0.001). Secondary: FVC improvement, VEGF-D reduction, 6-min walk improvement, QoL. After 12-month observation: benefits partially lost (FEV1 decline resumes), suggesting need for continuous therapy. mTOR inhibition does not eliminate LAM cells but controls their mTORC1-driven proliferation. Everolimus is used for TSC-associated LAM and for renal angiomyolipoma (EXIST-2). VEGF-D ≥800 pg/mL is a diagnostic biomarker (non-invasive diagnosis of LAM possible in right clinical context without biopsy).	sirolimus (target trough 5–15 ng/mL; start 2 mg/day PO, adjust to trough; continuous indefinitely for progressive LAM) everolimus 10 mg PO QD (TSC-associated LAM and renal AML; EXIST-2 dosing)	SRC-MILES-MCCORMACK-2011
ESCAT: clinical review pendingBIO-TSC1	TSC1 or TSC2 germline loss-of-function — Tuberous Sclerosis Complex with renal angiomyolipoma (AML) ≥3 cm or growing, at risk for hemorrhage (Wunderlich syndrome)	IB	Standard care SRC-NCCN-KIDNEY-2025: Level Category 1 (Supports, Sensitivity/Response)	Everolimus (mTOR inhibitor) is FDA-approved (2012) for renal angiomyolipoma (AML) associated with TSC. EXIST-2 phase III (Bissler et al., Lancet 2013): N=118 (everolimus 10 mg vs placebo); primary endpoint: AML response rate (≥50% reduction in sum of longest diameters of target AMLs). AML response: 42% (everolimus) vs 0% (placebo) (p<0.0001); mDOR: not reached. Disease stabilization: 96% vs 55%. Everolimus also reduces AML growth rate and risk of spontaneous hemorrhage (Wunderlich syndrome). In TSC patients with AMLs ≥3 cm, prophylactic everolimus is preferred to prophylactic embolization per current guidelines. Note: TSC1 germline is the biomarker for eligibility (Tuberous Sclerosis Complex diagnosis required); sporadic renal AML without TSC features are a different entity. ESCAT IB: phase III RCT data but for renal angiomyolipoma (benign disease context, not malignant RCC — thus IB not IA despite strong evidence).	everolimus 10 mg PO QD (TSC renal AML ≥3 cm growing/at risk; EXIST-2 regimen; monitor trough levels target 3–15 ng/mL)	SRC-NCCN-KIDNEY-2025

Primary current-line option

Standard plan

★ DEFAULT

Indication

IND-LAM-1L-SIROLIMUS

Regimen

Sirolimus monotherapy (progressive LAM)

Drugs + NSZU

Sirolimus (DRUG-SIROLIMUS) 2 mg PO once daily initially; titrate to target trough 5–15 ng/mL · Continuous; long-term treatment; monitor trough levels · PO ⚠ Out-of-pocket

Reason

Primary current-line option selected by ALGO-LAM-1L at step 2.

Pre-treatment investigations

Investigations before treatment start · critical / standard / desired · merged across tracks

ID	Name	Priority	Category	Where to order	Needed for
TEST-CBC	Complete Blood Count with Differential	Critical	lab	—	all tracks
TEST-CMP	Comprehensive Metabolic Panel	Critical	lab	—	all tracks

What NOT to do

Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity

Standard plan (IND-LAM-1L-SIROLIMUS)

Do NOT ignore sirolimus trough level monitoring — check 1–2 weeks post dose change; target 5–15 ng/mL
Do NOT initiate during active infections — mTOR inhibition impairs immune defense
Do NOT ignore new respiratory symptoms — non-infectious pneumonitis is a class effect
Do NOT co-administer with grapefruit juice or strong CYP3A4 inhibitors/inducers — markedly alters drug levels
Do NOT use during pregnancy — teratogenicity

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · Sirolimus monotherapy (progressive LAM)

28-day cycles × Long-term continuous

MDT brief

MDT talk tree (2 steps)

#	Owner	Topic	Action
1	molecular_geneticist	Specialist review	Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.
2	social_worker_case_manager	Specialist review	Plan includes drugs without NSZU reimbursement — patient access pathway must be assessed.

Skills (recommended) — for consideration (2)

Molecular geneticist / molecular oncologist recommended
Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.
Social worker / case manager recommended
Plan includes drugs without NSZU reimbursement — patient access pathway must be assessed.

Data quality

Usable with caveats. No critical default-track gap was found, but the MDT should review the listed caveats before final sign-off.

Biomarker coverage: 1/1 known (100%), 0 missing, 0 default-track gaps
Unevaluated RedFlags: RF-TSC-CONFIRMED-CARRIER

Technical MDT skill metadata (2/16 activated in this plan)

All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).

Specialist	skill_id	Version	Last reviewed	Domain
Cellular therapy specialist (CAR-T)	`cellular_therapy_specialist`	v0.1.0	2026-04-25	cellular_therapy
Clinical pharmacist	`clinical_pharmacist`	v0.1.0	2026-04-25	clinical_pharmacy
Hematologist / oncohematologist	`hematologist`	v0.1.0	2026-04-25	hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)	`hematopathologist`	v0.1.0	2026-04-25	hematopathology
Infectious disease / hepatology	`infectious_disease_hepatology`	v0.1.0	2026-04-25	infectious_diseases
Medical oncologist (solid-tumor chemotherapist)	`medical_oncologist`	v0.1.0	2026-04-25	solid_oncology
Molecular geneticist / molecular oncologist	`molecular_geneticist`	v0.1.0	2026-04-25	molecular_oncology
Palliative care	`palliative_care`	v0.1.0	2026-04-25	palliative_care
Pathologist (general)	`pathologist`	v0.1.0	2026-04-25	pathology
Primary care / family physician	`primary_care`	v0.1.0	2026-04-25	primary_care
Psycho-oncologist	`psychologist`	v0.1.0	2026-04-25	psychosocial
Radiation oncologist	`radiation_oncologist`	v0.1.0	2026-04-25	radiation_oncology
Radiologist	`radiologist`	v0.1.0	2026-04-25	diagnostic_imaging
Social worker / case manager	`social_worker_case_manager`	v0.1.0	2026-04-25	psychosocial
Surgical oncologist	`surgical_oncologist`	v0.1.0	2026-04-25	surgical_oncology
Transplant specialist (BMT)	`transplant_specialist`	v0.1.0	2026-04-25	cellular_therapy

Sources cited

SRC-MILES-MCCORMACK-2011: MILES: Sirolimus for Lymphangioleiomyomatosis (McCormack et al., NEJM 2011) ()

Experimental options (clinical trials)

Third plan track — open-enrollment trials from ClinicalTrials.gov. Render-time metadata; engine selection is not affected by this block (CHARTER §8.3). Last synced: 2026-08-18.

NCT	Title	Phase	Status	Sponsor	UA	Signals	Eligibility (excerpt)
NCT05676099	TSC Biosample Repository and Natural History Database	N/A	RECRUITING	National Tuberous Sclerosis Association	—	—

Verify recruitment status directly with the trial site. ctgov data can lag behind current UA-site status.

Option availability in Ukraine

Per-track UA registration · NSZU · cost · access pathway. Render-time metadata; engine selection does not depend on these fields (CHARTER §8.3).

Option	UA registration	NSZU	Cost orientation	Access pathway
Standard plan Sirolimus monotherapy (progressive LAM) (REG-SIROLIMUS-LAM) 1/1 component drug(s) not on NSZU formulary	✓ registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Trial · NCT05676099 TSC Biosample Repository and Natural History Database No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-08-18.

plan_id: PLAN-BMA-TSC1_LAM-V1 | version: 1 | generated: 2026-08-18T07:59:49.486311+00:00

Per FDA non-device CDS positioning (CHARTER §15): Outpatient oncology treatment planning to support tumor-board discussion. Not a medical device; not for autonomous clinical decision-making.

Per FDA non-device CDS positioning (CHARTER §15): Both treatment options below are presented for review. The engine's selection of a 'recommended' default does not constitute a clinical decision. Final treatment selection requires HCP judgment incorporating information not available to the system.

This document is an informational resource supporting tumor-board discussion (per CHARTER §11). It is not a system that makes clinical decisions. Every recommendation must be verified by the treating physician.