TreatmentResponseMonitoringChecker

URS & FS — User Requirements and Functional Specification

This document describes the controlled interface and behaviour of TreatmentResponseMonitoringChecker for Treatment Response Monitoring Checker.

Domain limits and critical parameters

• Performs molecular response evaluation per ESMO Precision Medicine Guidelines, NCCN Therapy Monitoring, CAP/CLIA §GEN.48800 and consensus molecular monitoring recommendations: molecular response classification (mCR: sustained clearance ≥2 timepoints; mPR: ≥50% VAF decrease from baseline; mSD: neither mPR nor mPD; mPD: ≥25% VAF increase from nadir OR new confirmed resistance variant; INDETERMINATE: technical limitations), VAF dynamics (baseline→nadir→current percent change, molecular clearance as
• ⚠️ Critical: Molecular response ≠ radiological response; integration of both mandatory. New resistance mutation = mPD EVEN IF target VAF decreasing. VAF comparison across different matrices (tissue vs plasma) INVALID. Single-timepoint clearance ≠ mCR; sustained confirmation required. ≥25% increase from nadir = mPD threshold (analogous to RECIST PD). Discordance requires clinical correlation, not automatic decision. Technical issues at any timepoint = INDETERMINATE assessment. Tool provides STRUC
• 5. Clearance Confirmation: Require ≥2 consecutive below-LOD timepoints for mCR declaration.

URS — User Requirements Specification

input.csv contract

PatientID,PrimaryTumorType,CurrentTherapy,TherapyLine,TherapyStartDate,DaysOnTherapy,BaselineVariant,BaselineVAF_Percent,BaselineDate,BaselineQC_Passed,NadirVAF_Percent,NadirDate,SampleID_Current,CurrentVAF_Percent,CurrentDate,CurrentQC_Passed,CurrentDepth_X,AssayLOD_Percent,CurrentAboveLOD,DaysSinceBaseline,DaysSinceNadir,NewResistanceVariant_Detected,NewResistanceVariant,NewVariantVAF_Percent,NewVariant_Confirmed,ResistanceMechanism,RECIST_Response,LastImaging_Date,DaysBetween_MolecularAndImaging,MolecularRadiological_Concordant,DiscordanceType,BothTimepoints_TechnicallyReliable,SampleType_Consistent,AssayPlatform_Consistent,ReliabilityConcern,Symptoms_Progressing,ECOG_Status,ActionableAlternative_Available,AlternativeTherapyOptions
PAT-LUNG-042,NSCLC,Osimertinib,First_Line,2026-03-15,85,EGFR:L858R,18.5,2026-03-10,true,0.8,2026-05-20,TX-2026-001,1.2,2026-06-08,true,15000,0.01,true,90,19,false,,0,false,,PR,2026-06-01,7,true,,true,true,true,,false,0,false,
PAT-CRC-055,CRC,Cetuximab+FOLFIRI,Second_Line,2026-01-10,150,KRAS_WT,0,2026-01-05,true,0,2026-01-05,TX-2026-002,8.5,2026-06-09,true,12000,0.01,true,155,155,true,KRAS:G12C,8.5,true,Off_Target_Bypass,PD,2026-06-05,4,true,,true,true,true,,true,1,true,Sotorasib;Adagrasib;Clinical_Trial
PAT-BRCA-061,Breast,Palbociclib+Letrozole,First_Line,2026-02-01,128,PIK3CA:H1047R,12.0,2026-01-28,true,0.3,2026-04-15,TX-2026-003,0.5,2026-06-08,true,18000,0.01,true,131,54,false,,0,false,,PD,2026-06-05,3,false,Molecular_PR_Radiological_PD,true,true,true,,false,0,true,Fulvestrant;Alpelisib

Input validation rules

FS — Functional Specification

Example output.json

{
  "utilityId": "treatmentresponsemonitoringchecker",
  "utilityFolder": "TreatmentResponseMonitoringChecker",
  "package": "LiquidBiopsy",
  "overallStatus": "PASS|WARNING|FAIL",
  "sourceFile": "input.csv",
  "processedAtUtc": "2026-06-10T00:00:00Z",
  "checks": [
    {
      "parameter": "PatientID",
      "value": "PAT-LUNG-042",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-001"
    },
    {
      "parameter": "PrimaryTumorType",
      "value": "NSCLC",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-002"
    },
    {
      "parameter": "CurrentTherapy",
      "value": "Osimertinib",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-003"
    },
    {
      "parameter": "TherapyLine",
      "value": "First_Line",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-004"
    },
    {
      "parameter": "TherapyStartDate",
      "value": "2026-03-15",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-005"
    },
    {
      "parameter": "DaysOnTherapy",
      "value": "85",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-006"
    },
    {
      "parameter": "BaselineVariant",
      "value": "EGFR:L858R",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-007"
    },
    {
      "parameter": "BaselineVAF_Percent",
      "value": "18.5",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-008"
    },
    {
      "parameter": "BaselineDate",
      "value": "2026-03-10",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-009"
    },
    {
      "parameter": "BaselineQC_Passed",
      "value": "true",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-010"
    },
    {
      "parameter": "NadirVAF_Percent",
      "value": "0.8",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-011"
    },
    {
      "parameter": "NadirDate",
      "value": "2026-05-20",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-012"
    }
  ],
  "criticalFindings": [],
  "warnings": [],
  "audit": {
    "inputHash": "sha256:<calculated at runtime>",
    "rulesVersion": "<utility executable version>",
    "documentation": "TreatmentResponseMonitoringChecker.documentation.html"
  }
}

Traceability matrix

IQ/OQ/PQ test scenarios

QA/QC and change control

• Do not rename columns without updating validator, documentation and test set.
• Retain input.csv, output.json, executable version and checksum.
• Before production use, perform IQ/OQ/PQ or equivalent CSV/CSA verification.
• Critical limits shall be verified against the approved specification, registration dossier and local SOPs.
• The utility provides structured QC decision support; final release decision remains with QA/QP and approved procedures.