| Biomarker | Variant | ESCAT | Evidence | Clinical significance | Drugs | Sources |
|---|---|---|---|---|---|---|
| ESCAT: clinical review pendingBIO-PTCH1 | PTCH1 loss-of-function (somatic — sporadic BCC; germline — Gorlin/Basal Cell Nevus Syndrome); activates HH pathway via SMO disinhibition | IA | Standard care
| PTCH1 loss is the primary molecular driver of BCC (~90% of sporadic cases and all Gorlin syndrome-associated BCCs). Loss of PTCH1 function disinhibits SMO, constitutively activating Hedgehog (HH) signaling. Therapeutic implication is identical to SMO-mutant BCC: SMO antagonists (vismodegib, sonidegib) block SMO activity downstream of PTCH1 and restore HH pathway suppression. FDA approvals for vismodegib (2012) and sonidegib (2015) for laBCC/mBCC apply regardless of whether the underlying driver is PTCH1 loss or SMO mutation — clinical eligibility is based solely on disease extent (locally advanced or metastatic) and surgical/radiation suitability, not on molecular testing. Gorlin syndrome (germline PTCH1): same therapeutic approach but radiation therapy is relatively contraindicated (radiation-induced BCC within field). Cemiplimab FDA-approved post-HHI (2021). See BMA-SMO-BCC for full efficacy data (ERIVANCE, BOLT trials) — the PTCH1 and SMO BMA entries share identical therapeutic recommendations; the distinction is clinically relevant for resistance mechanism (secondary SMO mutation in PTCH1-driven BCC after HHI = acquired SMO mutation) and for Gorlin syndrome genetic counseling. | vismodegib 150 mg PO QD (see BMA-SMO-BCC for full regimen details) sonidegib 200 mg PO QD with food cemiplimab 350 mg IV q3w (post-HHI) Gorlin syndrome: multidisciplinary surveillance (dermatology, ophthalmology, neurology, genetics); vismodegib for high-burden BCC with toxicity break strategy |
|
| ESCAT: clinical review pendingBIO-PTCH1-GERMLINE | PTCH1 germline pathogenic (NBCCS / Gorlin syndrome) | IIA |
Evidence cited from clinical guidelines; per-source evidence levels not yet structured. See Phase-2-of-CIViC-pivot for re-cite roadmap. | PTCH1 germline pathogenic variants cause Nevoid Basal Cell Carcinoma Syndrome (NBCCS / Gorlin syndrome) — characterized by multiple early-onset basal cell carcinomas (BCCs, often hundreds over a lifetime), odontogenic keratocysts of the jaw, palmar/plantar pits, macrocephaly, rib + skeletal anomalies, cardiac fibroma, and ~5% lifetime risk of desmoplastic-type medulloblastoma (SHH subgroup) — peak age 1-2 years. Confirmed-carrier surveillance protocol (per Bree & Shah 2011 / NCCN Skin): pediatric brain MRI q6mo from diagnosis through age 3 then annually through age 7 (medulloblastoma); whole-body dermatology q6mo from infancy for BCC detection (transition to q3mo after first BCC); jaw OPG / panoramic radiograph q1y from age 8 for odontogenic keratocyst; echocardiogram in infancy for cardiac fibroma; minimize ionizing radiation exposure (BCCs induced by EBRT — avoid radiotherapy for medulloblastoma when alternatives available). Vismodegib and sonidegib (Hedgehog-pathway smoothened inhibitors) are active for locally advanced/metastatic BCC and for BCC-burden reduction (off-label), surveillance-triggered. ESCAT IIA. | vismodegib 150 mg PO daily — locally advanced / metastatic BCC; off-label BCC-burden reduction in NBCCS (intolerance of recurrent surgery) sonidegib 200 mg PO daily — locally advanced BCC; off-label NBCCS BCC-burden reduction topical 5-fluorouracil / imiquimod — superficial BCC field therapy adjunct dermatology q3-6mo with photodynamic therapy / curettage for low-risk lesions; Mohs for high-risk sites oral/maxillofacial surgery follow-up for odontogenic keratocyst (recurrence-prone — marsupialization vs enucleation) minimize EBRT exposure (BCC induction in irradiation field is a known late effect) |
|
| ID | Name | Priority | Category | Where to order | Needed for |
|---|---|---|---|---|---|
| TEST-EXCISIONAL-SKIN-BIOPSY | Excisional skin biopsy | Critical | histology | — | all tracks |
| TEST-PREGNANCY | Beta-HCG | Critical | lab | — | all tracks |
| # | Owner | Topic | Action |
|---|---|---|---|
| 1 | molecular_geneticist | Biomarker status BLOCKING | What is the status of PTCH1 loss-of-function mutation (Patched-1) (BIO-PTCH1)? It is required by track(s): IND-BCC-1L-VISMODEGIB. Expected value: PTCH1 loss-of-function (HH pathway activation) — supports eligibility but not mandatory (HH activation assumed in locally advanced/metastatic BCC). |
| 2 | hematologist | Staging / disease burden | What is the current LDH? Marker of tumor burden and transformation. |
| 3 | molecular_geneticist | Biomarker status | What is the status of SMO activating mutation (Smoothened) (BIO-SMO)? It is required by track(s): IND-BCC-1L-SONIDEGIB. Expected value: SMO activating mutation — supports eligibility; HH pathway activation assumed in all laBCC. |
| 4 | clinical_pharmacist | Specialist review | Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication. |
| Missing biomarker | Label | MDT owner | Default track | Required by | Next action |
|---|---|---|---|---|---|
BIO-PTCH1 | PTCH1 loss-of-function mutation (Patched-1) | molecular_geneticist | yes | IND-BCC-1L-VISMODEGIB | Verify result, method, specimen, and report date before sign-off. Expected/constraint: PTCH1 loss-of-function (HH pathway activation) — supports eligibility but not mandatory (HH activation assumed in locally advanced/metastatic BCC) |
BIO-SMO | SMO activating mutation (Smoothened) | molecular_geneticist | no | IND-BCC-1L-SONIDEGIB | Verify result, method, specimen, and report date before sign-off. Expected/constraint: SMO activating mutation — supports eligibility; HH pathway activation assumed in all laBCC |
| Specialist | skill_id | Version | Last reviewed | Sign-offs | Domain |
|---|---|---|---|---|---|
| Cellular therapy specialist (CAR-T) | cellular_therapy_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
| Clinical pharmacist | clinical_pharmacist | v0.1.0 | 2026-04-25 | 0 | clinical_pharmacy |
| Hematologist / oncohematologist | hematologist | v0.1.0 | 2026-04-25 | 0 | hematology_oncology |
| Hematopathologist (lymphoma / leukemia / myeloma) | hematopathologist | v0.1.0 | 2026-04-25 | 0 | hematopathology |
| Infectious disease / hepatology | infectious_disease_hepatology | v0.1.0 | 2026-04-25 | 0 | infectious_diseases |
| Medical oncologist (solid-tumor chemotherapist) | medical_oncologist | v0.1.0 | 2026-04-25 | 0 | solid_oncology |
| Molecular geneticist / molecular oncologist | molecular_geneticist | v0.1.0 | 2026-04-25 | 0 | molecular_oncology |
| Palliative care | palliative_care | v0.1.0 | 2026-04-25 | 0 | palliative_care |
| Pathologist (general) | pathologist | v0.1.0 | 2026-04-25 | 0 | pathology |
| Primary care / family physician | primary_care | v0.1.0 | 2026-04-25 | 0 | primary_care |
| Psycho-oncologist | psychologist | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Radiation oncologist | radiation_oncologist | v0.1.0 | 2026-04-25 | 0 | radiation_oncology |
| Radiologist | radiologist | v0.1.0 | 2026-04-25 | 0 | diagnostic_imaging |
| Social worker / case manager | social_worker_case_manager | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Surgical oncologist | surgical_oncologist | v0.1.0 | 2026-04-25 | 0 | surgical_oncology |
| Transplant specialist (BMT) | transplant_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
No active trials matched this scenario in ctgov.
| Option | UA registration | NSZU | Cost orientation | Access pathway |
|---|---|---|---|---|
| Standard plan Vismodegib monotherapy (locally advanced / metastatic BCC) (REG-VISMODEGIB-BCC) 1/1 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Aggressive plan Sonidegib monotherapy (locally advanced BCC) (REG-SONIDEGIB-BCC) 1/1 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-08-03.