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NCT04578106

Omission of Surgery in Clinically Low-risk HER2positive Breast Cancer With High HER2 Addiction and a Complete Response Following Standard Anti-HER2-based Neoadjuvant Therapy

Version 3 to 4 · Fundacio Clinic Barcelona

Patch inspector

Version 3 to 4

24 operations 7 path groups ctgov_internal_history
ClinicalTrials.gov
Severity is deterministic uncalibrated triage metadata, not validated review priority. Operation-level severity is inferred from deterministic path rules. Rule matches shown per operation are approximate previews (they skip the pipeline's suppression passes); the authoritative classification is the stored event record.
Plain-language summary

Manual review pending.

Rules fired
contact_admin_changeenrollment_count_changeenrollment_type_changeterminal_status_changewhy_stopped_change
Value signals
[
  {
    "path": "/protocolSection/statusModule/primaryCompletionDateStruct/date",
    "signal": "timeline_actualized_earlier",
    "category": "timeline_actualized_earlier",
    "new_type": "ACTUAL",
    "old_type": "ESTIMATED",
    "severity": "low",
    "direction": "earlier",
    "new_value": "2024-07-16",
    "old_value": "2026-12",
    "delta_days": 868,
    "date_struct": "primaryCompletionDateStruct",
    "new_precision": "day",
    "old_precision": "month"
  },
  {
    "path": "/protocolSection/statusModule/completionDateStruct/date",
    "signal": "timeline_actualized_earlier",
    "category": "timeline_actualized_earlier",
    "new_type": "ACTUAL",
    "old_type": "ESTIMATED",
    "severity": "low",
    "direction": "earlier",
    "new_value": "2024-07-16",
    "old_value": "2026-12",
    "delta_days": 868,
    "date_struct": "completionDateStruct",
    "new_precision": "day",
    "old_precision": "month"
  },
  {
    "path": "/protocolSection/designModule/enrollmentInfo/count",
    "signal": "enrollment_count_change_ge_20pct",
    "category": "enrollment_change",
    "severity": "high",
    "new_value": 5,
    "old_value": 17,
    "pct_change": 0.7059
  },
  {
    "paths": [
      "/protocolSection/outcomesModule/primaryOutcomes/0/measure"
    ],
    "signal": "results_reconciliation_outcome_suppression",
    "category": "results_reconciliation",
    "severity": "low"
  }
]
Provenance
Source
ctgov_internal_history
Fetched
2026-06-18 19:14:26+00
Raw hash
a68b9ecbe4dbb00b60fceea292ad569cdd000698143e0c0351e550c1829fc245
Payload
Source URL
Primary outcomes Outcome measures that define the trial's primary evidence target. Triage: Critical 1 ops
replace /protocolSection/outcomesModule/primaryOutcomes/0/measure
Triage: Critical
Primary Outcome Change Operation 15
Matched rules
  • primary_outcome_any_change Any add/remove/replace under primary outcome measures is critical review priority.
Before
To evaluate the possibility of omission of surgery and sentinel lymph node dissection in clinically low-risk HER2-positive breast cancer with high HER2 addiction and a complete response following standard neoadjuvant chemotherapy and dual HER2 blockade.
After
Disease-free Survival at 3years
Design Trial model, phase, allocation, masking, arms, or interventions. Triage: High 2 ops
replace /protocolSection/designModule/enrollmentInfo/count
Triage: High
Enrollment Change Operation 13
Matched rules
  • enrollment_count_change Enrollment count changes can signal scope or feasibility shifts.
Before
17
After
5
replace /protocolSection/designModule/enrollmentInfo/type
Triage: High
Enrollment Change Operation 14
Matched rules
  • enrollment_type_change Enrollment type changes from anticipated to actual or similar are high review priority.
Before
ESTIMATED
After
ACTUAL
Secondary outcomes Additional endpoints and outcome descriptions. Triage: High 1 ops
add /protocolSection/outcomesModule/secondaryOutcomes
Triage: High
Secondary Outcome Change Operation 16
Matched rules
  • secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority.
After
[
  {
    "measure": "pCR Rate",
    "timeFrame": "pCR assessment was done following surgery after neoadjuvant therapy with paclitaxel and trastuzumzb/pertuzumab prior to adjuvant therapy",
    "description": "rate of pathological complete response (pCR) between the treatment groups by HR status"
  },
  {
    "measure": "Patient Reported Outcomes (Global Health Status)",
    "timeFrame": "The questionnaire was filled by the patients at screening and post adjuvant therapy.",
    "description": "<p>The EORTC QLQ-C30 was used to assess Health-Related Quality of Life (QoL).\nThe measure consists of five functional scales (physical, role, cognitive, emotional, and social).\nFor this study, raw scores were used without any transformation.\nThe functional scales consist of multiple items (questions 1-28) scored on a 1-4 scale (1 = not at all, 4 = very much).\nHigher scores indicate worse functioning.\nTo assess the effect of standard therapy (surgery after neoadjuvant therapy) vs. investigational therapy (omission of surgery), the global health status is reported in each of these populations before and after treatment.</p><p>The Global Health Status (GHS) score is derived from two items (Q29 and Q30), each scored on a 1-7 scale (1 = very poor, 7 = excellent).</p><p>Scoring method: GHS = (Q29 + Q30) &#x2F; 2 Raw score range: Minimum = (1 + 1) &#x2F; 2 = 1; Maximum = (7 + 7) &#x2F;2 = 7</p>"
  }
]
Status and stopping reason Recruitment status, termination, suspension, withdrawal, or why-stopped text. Triage: High 2 ops
replace /protocolSection/statusModule/overallStatus
Triage: High
Status Termination Operation 2
Matched rules
  • terminal_status_change Status changed to terminated, suspended, or withdrawn; whyStopped content determines whether critical review is warranted.
Before
RECRUITING
After
TERMINATED
add /protocolSection/statusModule/whyStopped
Triage: High
Status Termination Operation 9
Matched rules
  • why_stopped_change Why-stopped changes explain discontinuation and need review.
After
The study was prematurely halted primarily due to low patient accrual.
Despite efforts to optimize recruitment, the enrollment rate remained insufficient to meet the predefined targets, and continuation was deemed unfeasible
Timeline Start, primary completion, and completion date movement. Triage: Medium 4 ops
replace /protocolSection/statusModule/primaryCompletionDateStruct/date
Triage: Medium
Timeline Shift Operation 3
Matched rules
  • primary_completion_timeline_change Primary completion date changes are operational timeline signals.
Before
2026-12
After
2024-07-16
replace /protocolSection/statusModule/primaryCompletionDateStruct/type
Triage: Medium
Timeline Shift Operation 4
Matched rules
  • primary_completion_timeline_change Primary completion date changes are operational timeline signals.
Before
ESTIMATED
After
ACTUAL
replace /protocolSection/statusModule/completionDateStruct/date
Triage: Medium
Timeline Shift Operation 5
Matched rules
  • completion_timeline_change Completion date changes are operational timeline signals.
Before
2026-12
After
2024-07-16
replace /protocolSection/statusModule/completionDateStruct/type
Triage: Medium
Timeline Shift Operation 6
Matched rules
  • completion_timeline_change Completion date changes are operational timeline signals.
Before
ESTIMATED
After
ACTUAL
Contacts and locations Site, contact, and location updates that are usually operational. Triage: Low 4 ops
remove /protocolSection/contactsLocationsModule/centralContacts
Triage: Low
Administrative Contact Change Operation 17
Matched rules
  • contact_admin_change Central contact updates are usually administrative.
Before
[
  {
    "name": "Laia Arenas",
    "role": "CONTACT",
    "email": "ELPIS@clinic.cat",
    "phone": "93 2275400",
    "phoneExt": "3456"
  }
]
remove /protocolSection/contactsLocationsModule/locations/0/status
Triage: Uncategorized
Uncategorized Operation 18
Before
RECRUITING
remove /protocolSection/contactsLocationsModule/locations/0/contacts
Triage: Uncategorized
Uncategorized Operation 19
Before
[
  {
    "name": "Laia Arenas",
    "role": "CONTACT",
    "email": "elpis@clinic.cat",
    "phone": "+34 93 227 54 00"
  }
]
add /protocolSection/contactsLocationsModule/locations/0/state
Triage: Uncategorized
Uncategorized Operation 20
After
Barcelona
Other registry fields Changes outside the current high-signal rule families. Triage: Uncategorized 10 ops
replace /protocolSection/statusModule/statusVerifiedDate
Triage: Uncategorized
Uncategorized Operation 1
Before
2024-05
After
2026-01
replace /protocolSection/statusModule/lastUpdateSubmitDate
Triage: Uncategorized
Uncategorized Operation 7
Before
2024-05-11
After
2026-01-02
replace /protocolSection/statusModule/lastUpdatePostDateStruct/date
Triage: Uncategorized
Uncategorized Operation 8
Before
2024-05-14
After
2026-01-06
add /protocolSection/statusModule/resultsFirstSubmitDate
Triage: Uncategorized
Uncategorized Operation 10
After
2025-09-05
add /protocolSection/statusModule/resultsFirstSubmitQcDate
Triage: Uncategorized
Uncategorized Operation 11
After
2026-01-02
add /protocolSection/statusModule/resultsFirstPostDateStruct
Triage: Uncategorized
Uncategorized Operation 12
After
{
  "date": "2026-01-06",
  "type": "ACTUAL"
}
remove /annotationSection
Triage: Uncategorized
Uncategorized Operation 21
Before
{
  "annotationModule": {
    "unpostedAnnotation": {
      "unpostedEvents": [
        {
          "date": "2025-09-05",
          "type": "RELEASE"
        },
        {
          "date": "2025-09-26",
          "type": "RESET"
        },
        {
          "date": "2025-12-10",
          "type": "RELEASE"
        },
        {
          "date": "2025-12-30",
          "type": "RESET"
        }
      ],
      "unpostedResponsibleParty": "Fundacio Clinic Barcelona"
    }
  }
}
replace /hasResults
Triage: Uncategorized
Uncategorized Operation 22
Before
false
After
true
add /resultsSection
Triage: Uncategorized
Uncategorized Operation 23
After
{
  "moreInfoModule": {
    "pointOfContact": {
      "email": "topascual@clinic.cat",
      "phone": "932275400",
      "title": "Dr. Tomas Pascual",
      "organization": "Hospital Clínic de Barcelona"
    },
    "certainAgreement": {
      "piSponsorEmployee": true
    }
  },
  "adverseEventsModule": {
    "timeFrame": "Study treatment duration - 1 year (neoadjuvant and adjuvant therapy)",
    "eventGroups": [
      {
        "id": "EG000",
        "title": "Treatment Arm (Treatment With Paclitaxel)",
        "description": "<p>Treatment in women with primary operable HER2-positive, HER2-enriched(HER2-E)&#x2F;ERBB2-high breast cancer according to PAM50 intrinsic subtype and a ERBB2 pre-defined cutoff (high vs low ERBB2 expression):</p><ul><li>Tumor size ≤ 2 cm: Paclitaxel&#x2F;trastuzumab&#x2F;pertuzumab (TDM-1 if residual disease)</li><li>Tumor size &gt; 2 cm and ≤ 4cm: Antracycline based chemotherapy followed by Paclitaxel&#x2F;trastuzumab&#x2F;pertuzumab (TDM-1 if residual disease)</li></ul>",
        "otherNumAtRisk": 5,
        "deathsNumAtRisk": 5,
        "otherNumAffected": 5,
        "seriousNumAtRisk": 5,
        "deathsNumAffected": 0,
        "seriousNumAffected": 0
      },
      {
        "id": "EG001",
        "title": "Treatment Arm (Treatment With Trastuzumab)",
        "description": "<p>Treatment in women with primary operable HER2-positive, HER2-enriched(HER2-E)&#x2F;ERBB2-high breast cancer according to PAM50 intrinsic subtype and a ERBB2 pre-defined cutoff (high vs low ERBB2 expression):</p><ul><li>Tumor size ≤ 2 cm: Paclitaxel&#x2F;trastuzumab&#x2F;pertuzumab (TDM-1 if residual disease)</li><li>Tumor size &gt; 2 cm and ≤ 4cm: Antracycline based chemotherapy followed by Paclitaxel&#x2F;trastuzumab&#x2F;pertuzumab (TDM-1 if residual disease)</li></ul>",
        "otherNumAtRisk": 5,
        "deathsNumAtRisk": 5,
        "otherNumAffected": 5,
        "seriousNumAtRisk": 5,
        "deathsNumAffected": 0,
        "seriousNumAffected": 0
      },
      {
        "id": "EG002",
        "title": "Treatment Arm (Treatment With Pertuzumab)",
        "description": "<p>Treatment in women with primary operable HER2-positive, HER2-enriched(HER2-E)&#x2F;ERBB2-high breast cancer according to PAM50 intrinsic subtype and a ERBB2 pre-defined cutoff (high vs low ERBB2 expression):</p><ul><li>Tumor size ≤ 2 cm: Paclitaxel&#x2F;trastuzumab&#x2F;pertuzumab (TDM-1 if residual disease)</li><li>Tumor size &gt; 2 cm and ≤ 4cm: Antracycline based chemotherapy followed by Paclitaxel&#x2F;trastuzumab&#x2F;pertuzumab (TDM-1 if residual disease)</li></ul>",
        "otherNumAtRisk": 5,
        "deathsNumAtRisk": 5,
        "otherNumAffected": 5,
        "seriousNumAtRisk": 5,
        "deathsNumAffected": 0,
        "seriousNumAffected": 0
      },
      {
        "id": "EG003",
        "title": "Treatment Arm (Adjuvant Treatment With TDM1)",
        "description": "TDM-1 administered on Day 1 of a 3-week cycle q3w at a doce of 3.6 mg&#x2F;kg IV as adjuvant treatment in patients of the treatment population with non-complete response in the neoadjuvant setting",
        "otherNumAtRisk": 3,
        "deathsNumAtRisk": 3,
        "otherNumAffected": 3,
        "seriousNumAtRisk": 3,
        "deathsNumAffected": 0,
        "seriousNumAffected": 0
      }
    ],
    "otherEvents": [
      {
        "term": "alopecia",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 7,
            "numAffected": 4
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 0,
            "numAffected": 0
          }
        ],
        "organSystem": "Skin and subcutaneous tissue disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "asthenia",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 2,
            "numAffected": 2
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 3,
            "numAffected": 1
          }
        ],
        "organSystem": "General disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "dysguesia",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 2,
            "numAffected": 2
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 0,
            "numAffected": 0
          }
        ],
        "organSystem": "Metabolism and nutrition disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "anemia",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 0,
            "numAffected": 0
          }
        ],
        "organSystem": "Blood and lymphatic system disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "arthralgia",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 0,
            "numAffected": 0
          }
        ],
        "organSystem": "Musculoskeletal and connective tissue disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "headache",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 2,
            "numAffected": 2
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 0,
            "numAffected": 0
          }
        ],
        "organSystem": "Nervous system disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "diarrhea",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 4,
            "numAffected": 4
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 4,
            "numAffected": 4
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 0,
            "numAffected": 0
          }
        ],
        "organSystem": "Gastrointestinal disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "erythema face and hands",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 0,
            "numAffected": 0
          }
        ],
        "organSystem": "Skin and subcutaneous tissue disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "erythema arms and hands",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 3,
            "numAffected": 3
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 0,
            "numAffected": 0
          }
        ],
        "organSystem": "Skin and subcutaneous tissue disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "feet erythema",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 0,
            "numAffected": 0
          }
        ],
        "organSystem": "Skin and subcutaneous tissue disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "hands neurotoxicity",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 0,
            "numAffected": 0
          }
        ],
        "organSystem": "Nervous system disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "hiporexya",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 1,
            "numAffected": 1
          }
        ],
        "organSystem": "Metabolism and nutrition disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "mucositis",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 0,
            "numAffected": 0
          }
        ],
        "organSystem": "Respiratory, thoracic and mediastinal disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "neurotoxicity in foot",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 0,
            "numAffected": 0
          }
        ],
        "organSystem": "Nervous system disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "occasional epistaxis",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 0,
            "numAffected": 0
          }
        ],
        "organSystem": "Respiratory, thoracic and mediastinal disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "onychodystrophy",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 0,
            "numAffected": 0
          }
        ],
        "organSystem": "Skin and subcutaneous tissue disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "onycholysis",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 0,
            "numAffected": 0
          }
        ],
        "organSystem": "Skin and subcutaneous tissue disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "plantar erythema",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 0,
            "numAffected": 0
          }
        ],
        "organSystem": "Skin and subcutaneous tissue disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "cough",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 0,
            "numAffected": 0
          }
        ],
        "organSystem": "Respiratory, thoracic and mediastinal disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "erythematous reaction",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 0,
            "numAffected": 0
          }
        ],
        "organSystem": "Skin and subcutaneous tissue disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "muscle pain",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 1,
            "numAffected": 1
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 0,
            "numAffected": 0
          }
        ],
        "organSystem": "Musculoskeletal and connective tissue disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "plaquetopenia",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 2,
            "numAffected": 1
          }
        ],
        "organSystem": "Blood and lymphatic system disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "decrease in hemoglobin",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 1,
            "numAffected": 1
          }
        ],
        "organSystem": "Blood and lymphatic system disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "increase of total bilirubine",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 1,
            "numAffected": 1
          }
        ],
        "organSystem": "Hepatobiliary disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "alat increase",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 4,
            "numAffected": 3
          }
        ],
        "organSystem": "Hepatobiliary disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "asat increase",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 2,
            "numAffected": 2
          }
        ],
        "organSystem": "Hepatobiliary disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "epigastralgia",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 2,
            "numAffected": 2
          }
        ],
        "organSystem": "Gastrointestinal disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      },
      {
        "term": "increase of alkaline phosphatase",
        "stats": [
          {
            "groupId": "EG000",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG001",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG002",
            "numAtRisk": 5,
            "numEvents": 0,
            "numAffected": 0
          },
          {
            "groupId": "EG003",
            "numAtRisk": 3,
            "numEvents": 2,
            "numAffected": 2
          }
        ],
        "organSystem": "Hepatobiliary disorders",
        "assessmentType": "SYSTEMATIC_ASSESSMENT",
        "sourceVocabulary": "CTCAE (5)"
      }
    ],
    "frequencyThreshold": "5"
  },
  "outcomeMeasuresModule": {
    "outcomeMeasures": [
      {
        "type": "PRIMARY",
        "title": "Disease-free Survival at 3years",
        "denoms": [
          {
            "units": "Participants",
            "counts": [
              {
                "value": "0",
                "groupId": "OG000"
              }
            ]
          }
        ],
        "groups": [
          {
            "id": "OG000",
            "title": "Omision of Surgery (Complete Response)",
            "description": "After completion of neoadjuvant therapy, if no invasive tumor cells and no in situ disease are identified in the stereotactic-guided VAB (complete response), patients will be eligible to omit loco-regional surgery"
          }
        ],
        "paramType": "MEDIAN",
        "timeFrame": "3 years",
        "description": "To estimate the loco-regional invasive disease-free survival (LR-IDFS) at 3-year of patients who achieve a complete response based on imaging and a stereotactic-guided vacuum-assisted breast biopsy, and omit loco-regional surgery.",
        "unitOfMeasure": "years",
        "dispersionType": "95% Confidence Interval",
        "reportingStatus": "POSTED",
        "populationDescription": "After completion of neoadjuvant therapy with paclitaxel and Trastuzumab&#x2F;pertuzumab, out of 5 patients, only 3 patients showed complete response (assessed by MRI) and 2 patients (no stereo-guided VAB assessment) did not undergo surgery.\nHowever, the participants were lost to follow-up before 3-year assessments, so no evaluable 3-year survival data are available"
      },
      {
        "type": "SECONDARY",
        "title": "pCR Rate",
        "denoms": [
          {
            "units": "Participants",
            "counts": [
              {
                "value": "1",
                "groupId": "OG000"
              },
              {
                "value": "2",
                "groupId": "OG001"
              }
            ]
          }
        ],
        "groups": [
          {
            "id": "OG000",
            "title": "HR Positive",
            "description": "patients that are hormone receptor (HR) positive (assessment at baseline)"
          },
          {
            "id": "OG001",
            "title": "HR Negative",
            "description": "Patients that are hormone receptor (HR) negative (assessed at baseline)"
          }
        ],
        "classes": [
          {
            "categories": [
              {
                "measurements": [
                  {
                    "value": "0",
                    "groupId": "OG000"
                  },
                  {
                    "value": "2",
                    "groupId": "OG001"
                  }
                ]
              }
            ]
          }
        ],
        "paramType": "COUNT_OF_PARTICIPANTS",
        "timeFrame": "pCR assessment was done following surgery after neoadjuvant therapy with paclitaxel and trastuzumzb&#x2F;pertuzumab prior to adjuvant therapy",
        "description": "rate of pathological complete response (pCR) between the treatment groups by HR status",
        "unitOfMeasure": "Participants",
        "reportingStatus": "POSTED",
        "populationDescription": "While total number of HR positive patients and HR negative patients in the overall treatment group is 2 and 3 respectively, only 1 patient in the former and 2 patients in the later group were evaluated for pCR at surgery"
      },
      {
        "type": "SECONDARY",
        "title": "Patient Reported Outcomes (Global Health Status)",
        "denoms": [
          {
            "units": "Participants",
            "counts": [
              {
                "value": "3",
                "groupId": "OG000"
              },
              {
                "value": "2",
                "groupId": "OG001"
              },
              {
                "value": "2",
                "groupId": "OG002"
              },
              {
                "value": "2",
                "groupId": "OG003"
              }
            ]
          }
        ],
        "groups": [
          {
            "id": "OG000",
            "title": "Patients Who Underwent Surgery (Assessment at Screening)",
            "description": "<p>Of the treatment population, those patients who underwent surgery post neoadjuvant therapy.</p><p>The assessment time period is at screening</p>"
          },
          {
            "id": "OG001",
            "title": "Patients Who Underwent Surgery (Assessment After Adjuvant Therapy)",
            "description": "<p>Of the treatment population, those patients who underwent surgery post neoadjuvant therapy.</p><p>The assessment time period is after adjuvant therapy</p>"
          },
          {
            "id": "OG002",
            "title": "Patients With Omission of Surgery (Assessment at Screening)",
            "description": "<p>Of the treatment population, those patients with omission of surgery post neoadjuvant therapy.</p><p>The assessment time period is at screening</p>"
          },
          {
            "id": "OG003",
            "title": "Patients With Omission of Surgery (Assessment After Adjuvant Therapy)",
            "description": "<p>Of the treatment population, those patients who underwent surgery post neoadjuvant therapy.</p><p>The assessment time period is after adjuvant therapy</p>"
          }
        ],
        "classes": [
          {
            "categories": [
              {
                "measurements": [
                  {
                    "value": "5",
                    "groupId": "OG000",
                    "lowerLimit": "5",
                    "upperLimit": "6"
                  },
                  {
                    "value": "4",
                    "groupId": "OG001",
                    "lowerLimit": "3.5",
                    "upperLimit": "4.5"
                  },
                  {
                    "value": "5.25",
                    "groupId": "OG002",
                    "lowerLimit": "4.5",
                    "upperLimit": "6"
                  },
                  {
                    "value": "5",
                    "groupId": "OG003",
                    "lowerLimit": "4",
                    "upperLimit": "6"
                  }
                ]
              }
            ]
          }
        ],
        "paramType": "MEDIAN",
        "timeFrame": "The questionnaire was filled by the patients at screening and post adjuvant therapy.",
        "description": "<p>The EORTC QLQ-C30 was used to assess Health-Related Quality of Life (QoL).\nThe measure consists of five functional scales (physical, role, cognitive, emotional, and social).\nFor this study, raw scores were used without any transformation.\nThe functional scales consist of multiple items (questions 1-28) scored on a 1-4 scale (1 = not at all, 4 = very much).\nHigher scores indicate worse functioning.\nTo assess the effect of standard therapy (surgery after neoadjuvant therapy) vs. investigational therapy (omission of surgery), the global health status is reported in each of these populations before and after treatment.</p><p>The Global Health Status (GHS) score is derived from two items (Q29 and Q30), each scored on a 1-7 scale (1 = very poor, 7 = excellent).</p><p>Scoring method: GHS = (Q29 + Q30) &#x2F; 2 Raw score range: Minimum = (1 + 1) &#x2F; 2 = 1; Maximum = (7 + 7) &#x2F;2 = 7</p>",
        "unitOfMeasure": "score on a scale",
        "dispersionType": "Full Range",
        "reportingStatus": "POSTED",
        "populationDescription": "Out of the treatment population, 3 patients underwent surgery post neoadjuvant therapy (standard therapy) and 2 patients did not undergo surgery (investigative therapy).\nAll the patients of both the groups completed the patient reported outcomes questionaire at screening. 1 patient from the patient group that underwent surgery did not complete the questionnaire after adjuvant therapy."
      }
    ]
  },
  "participantFlowModule": {
    "groups": [
      {
        "id": "FG000",
        "title": "Treatment Arm",
        "description": "<p>Treatment in women with primary operable HER2-positive, HER2-enriched(HER2-E)&#x2F;ERBB2-high breast cancer according to PAM50 intrinsic subtype and a ERBB2 pre-defined cutoff (high vs low ERBB2 expression):</p><ul><li>Tumor size ≤ 2 cm: Paclitaxel&#x2F;trastuzumab&#x2F;pertuzumab (TDM-1 if residual disease)</li><li>Tumor size &gt; 2 cm and ≤ 4cm: Antracycline based chemotherapy followed by Paclitaxel&#x2F;trastuzumab&#x2F;pertuzumab (TDM-1 if residual disease)</li></ul>"
      }
    ],
    "periods": [
      {
        "title": "Study treatment",
        "milestones": [
          {
            "type": "STARTED",
            "achievements": [
              {
                "groupId": "FG000",
                "numSubjects": "5"
              }
            ]
          },
          {
            "type": "COMPLETED",
            "achievements": [
              {
                "groupId": "FG000",
                "numSubjects": "5"
              }
            ]
          },
          {
            "type": "NOT COMPLETED",
            "achievements": [
              {
                "groupId": "FG000",
                "numSubjects": "0"
              }
            ]
          }
        ]
      },
      {
        "title": "Follow-up after 1 year",
        "milestones": [
          {
            "type": "STARTED",
            "achievements": [
              {
                "groupId": "FG000",
                "numSubjects": "5"
              }
            ]
          },
          {
            "type": "COMPLETED",
            "achievements": [
              {
                "groupId": "FG000",
                "numSubjects": "4"
              }
            ]
          },
          {
            "type": "NOT COMPLETED",
            "achievements": [
              {
                "groupId": "FG000",
                "numSubjects": "1"
              }
            ]
          }
        ],
        "dropWithdraws": [
          {
            "type": "Lost to Follow-up",
            "reasons": [
              {
                "groupId": "FG000",
                "numSubjects": "1"
              }
            ]
          }
        ]
      },
      {
        "title": "Follow up at 3 yrs",
        "milestones": [
          {
            "type": "STARTED",
            "achievements": [
              {
                "groupId": "FG000",
                "numSubjects": "4"
              }
            ]
          },
          {
            "type": "COMPLETED",
            "achievements": [
              {
                "groupId": "FG000",
                "numSubjects": "0"
              }
            ]
          },
          {
            "type": "NOT COMPLETED",
            "achievements": [
              {
                "groupId": "FG000",
                "numSubjects": "4"
              }
            ]
          }
        ]
      }
    ],
    "recruitmentDetails": "Overall, 20 patients were screened for the study in a single study centre (clinical setting) over the duration of 18 months.\nA total of 5 patients were finally selected for the study treatment after meeting all the inclusion criteria and signing the ICF",
    "preAssignmentDetails": "<p>Out of 20 patients screened, 13 patients did not fulfill the study criteria (PAM50 subtype other than HER2-Enriched, ERBB2 high, liver metastasis, multicentric tumor).</p><p>Finally only 5 patients that fulfilled all eligibility criteria and signed the ICF were included</p>"
  },
  "baselineCharacteristicsModule": {
    "denoms": [
      {
        "units": "Participants",
        "counts": [
          {
            "value": "5",
            "groupId": "BG000"
          }
        ]
      }
    ],
    "groups": [
      {
        "id": "BG000",
        "title": "Treatment Arm",
        "description": "<p>Treatment in women with primary operable HER2-positive, HER2-enriched(HER2-E)&#x2F;ERBB2-high breast cancer according to PAM50 intrinsic subtype and a ERBB2 pre-defined cutoff (high vs low ERBB2 expression):</p><ul><li>Tumor size ≤ 2 cm: Paclitaxel&#x2F;trastuzumab&#x2F;pertuzumab (TDM-1 if residual disease)</li><li>Tumor size &gt; 2 cm and ≤ 4cm: Antracycline based chemotherapy followed by Paclitaxel&#x2F;trastuzumab&#x2F;pertuzumab (TDM-1 if residual disease)</li></ul>"
      }
    ],
    "measures": [
      {
        "title": "Age, Customized",
        "classes": [
          {
            "title": "&gt;= 40 yrs",
            "categories": [
              {
                "measurements": [
                  {
                    "value": "5",
                    "groupId": "BG000"
                  }
                ]
              }
            ]
          }
        ],
        "paramType": "NUMBER",
        "unitOfMeasure": "participants"
      },
      {
        "title": "Sex: Female, Male",
        "classes": [
          {
            "categories": [
              {
                "title": "Female",
                "measurements": [
                  {
                    "value": "5",
                    "groupId": "BG000"
                  }
                ]
              },
              {
                "title": "Male",
                "measurements": [
                  {
                    "value": "0",
                    "groupId": "BG000"
                  }
                ]
              }
            ]
          }
        ],
        "paramType": "COUNT_OF_PARTICIPANTS",
        "unitOfMeasure": "Participants"
      },
      {
        "title": "Race&#x2F;Ethnicity, Customized",
        "classes": [
          {
            "title": "Caucasian",
            "categories": [
              {
                "measurements": [
                  {
                    "value": "5",
                    "groupId": "BG000"
                  }
                ]
              }
            ]
          }
        ],
        "paramType": "NUMBER",
        "unitOfMeasure": "participants"
      },
      {
        "title": "Region of Enrollment",
        "classes": [
          {
            "title": "Spain",
            "categories": [
              {
                "measurements": [
                  {
                    "value": "5",
                    "groupId": "BG000"
                  }
                ]
              }
            ]
          }
        ],
        "paramType": "NUMBER",
        "unitOfMeasure": "participants"
      },
      {
        "title": "Menopausal Status",
        "classes": [
          {
            "title": "Postmenopausal (min 12 mnths without menses before neoadyuvance treatment)",
            "categories": [
              {
                "measurements": [
                  {
                    "value": "4",
                    "groupId": "BG000"
                  }
                ]
              }
            ]
          },
          {
            "title": "premenopausal",
            "categories": [
              {
                "measurements": [
                  {
                    "value": "1",
                    "groupId": "BG000"
                  }
                ]
              }
            ]
          }
        ],
        "paramType": "NUMBER",
        "unitOfMeasure": "participants"
      },
      {
        "title": "ECOG baseline",
        "classes": [
          {
            "title": "Grade 0",
            "categories": [
              {
                "measurements": [
                  {
                    "value": "4",
                    "groupId": "BG000"
                  }
                ]
              }
            ]
          },
          {
            "title": "Grade 1",
            "categories": [
              {
                "measurements": [
                  {
                    "value": "1",
                    "groupId": "BG000"
                  }
                ]
              }
            ]
          }
        ],
        "paramType": "NUMBER",
        "description": "Scale: Grades 0-4 Grade 0 - Fully active able to carry on all pre-disease performance without restriction; Grade 1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature e.g.\nlight house work office work; Grade 2 - Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours Grade 3 - Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours Grade 4 - Completely disabled; cannot carry on any selfcare; totally confined to bed or chair",
        "unitOfMeasure": "participants"
      },
      {
        "title": "Previous cancer history",
        "classes": [
          {
            "title": "Yes",
            "categories": [
              {
                "measurements": [
                  {
                    "value": "0",
                    "groupId": "BG000"
                  }
                ]
              }
            ]
          },
          {
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add /documentSection
Triage: Uncategorized
Uncategorized Operation 24
After
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          },
          {
            "term": "muscle pain",
            "stats": [
              {
                "groupId": "EG000",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG001",
                "numAtRisk": 5,
                "numEvents": 1,
                "numAffected": 1
              },
              {
                "groupId": "EG002",
                "numAtRisk": 5,
                "numEvents": 1,
                "numAffected": 1
              },
              {
                "groupId": "EG003",
                "numAtRisk": 3,
                "numEvents": 0,
                "numAffected": 0
              }
            ],
            "organSystem": "Musculoskeletal and connective tissue disorders",
            "assessmentType": "SYSTEMATIC_ASSESSMENT",
            "sourceVocabulary": "CTCAE (5)"
          },
          {
            "term": "plaquetopenia",
            "stats": [
              {
                "groupId": "EG000",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG001",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG002",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG003",
                "numAtRisk": 3,
                "numEvents": 2,
                "numAffected": 1
              }
            ],
            "organSystem": "Blood and lymphatic system disorders",
            "assessmentType": "SYSTEMATIC_ASSESSMENT",
            "sourceVocabulary": "CTCAE (5)"
          },
          {
            "term": "decrease in hemoglobin",
            "stats": [
              {
                "groupId": "EG000",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG001",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG002",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG003",
                "numAtRisk": 3,
                "numEvents": 1,
                "numAffected": 1
              }
            ],
            "organSystem": "Blood and lymphatic system disorders",
            "assessmentType": "SYSTEMATIC_ASSESSMENT",
            "sourceVocabulary": "CTCAE (5)"
          },
          {
            "term": "increase of total bilirubine",
            "stats": [
              {
                "groupId": "EG000",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG001",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG002",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG003",
                "numAtRisk": 3,
                "numEvents": 1,
                "numAffected": 1
              }
            ],
            "organSystem": "Hepatobiliary disorders",
            "assessmentType": "SYSTEMATIC_ASSESSMENT",
            "sourceVocabulary": "CTCAE (5)"
          },
          {
            "term": "alat increase",
            "stats": [
              {
                "groupId": "EG000",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG001",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG002",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG003",
                "numAtRisk": 3,
                "numEvents": 4,
                "numAffected": 3
              }
            ],
            "organSystem": "Hepatobiliary disorders",
            "assessmentType": "SYSTEMATIC_ASSESSMENT",
            "sourceVocabulary": "CTCAE (5)"
          },
          {
            "term": "asat increase",
            "stats": [
              {
                "groupId": "EG000",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG001",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG002",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG003",
                "numAtRisk": 3,
                "numEvents": 2,
                "numAffected": 2
              }
            ],
            "organSystem": "Hepatobiliary disorders",
            "assessmentType": "SYSTEMATIC_ASSESSMENT",
            "sourceVocabulary": "CTCAE (5)"
          },
          {
            "term": "epigastralgia",
            "stats": [
              {
                "groupId": "EG000",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG001",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG002",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG003",
                "numAtRisk": 3,
                "numEvents": 2,
                "numAffected": 2
              }
            ],
            "organSystem": "Gastrointestinal disorders",
            "assessmentType": "SYSTEMATIC_ASSESSMENT",
            "sourceVocabulary": "CTCAE (5)"
          },
          {
            "term": "increase of alkaline phosphatase",
            "stats": [
              {
                "groupId": "EG000",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG001",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG002",
                "numAtRisk": 5,
                "numEvents": 0,
                "numAffected": 0
              },
              {
                "groupId": "EG003",
                "numAtRisk": 3,
                "numEvents": 2,
                "numAffected": 2
              }
            ],
            "organSystem": "Hepatobiliary disorders",
            "assessmentType": "SYSTEMATIC_ASSESSMENT",
            "sourceVocabulary": "CTCAE (5)"
          }
        ],
        "frequencyThreshold": "5"
      },
      "outcomeMeasuresModule": {
        "outcomeMeasures": [
          {
            "type": "PRIMARY",
            "title": "Disease-free Survival at 3years",
            "denoms": [
              {
                "units": "Participants",
                "counts": [
                  {
                    "value": "0",
                    "groupId": "OG000"
                  }
                ]
              }
            ],
            "groups": [
              {
                "id": "OG000",
                "title": "Omision of Surgery (Complete Response)",
                "description": "After completion of neoadjuvant therapy, if no invasive tumor cells and no in situ disease are identified in the stereotactic-guided VAB (complete response), patients will be eligible to omit loco-regional surgery"
              }
            ],
            "paramType": "MEDIAN",
            "timeFrame": "3 years",
            "description": "To estimate the loco-regional invasive disease-free survival (LR-IDFS) at 3-year of patients who achieve a complete response based on imaging and a stereotactic-guided vacuum-assisted breast biopsy, and omit loco-regional surgery.",
            "unitOfMeasure": "years",
            "dispersionType": "95% Confidence Interval",
            "reportingStatus": "POSTED",
            "populationDescription": "After completion of neoadjuvant therapy with paclitaxel and Trastuzumab&#x2F;pertuzumab, out of 5 patients, only 3 patients showed complete response (assessed by MRI) and 2 patients (no stereo-guided VAB assessment) did not undergo surgery.\nHowever, the participants were lost to follow-up before 3-year assessments, so no evaluable 3-year survival data are available"
          },
          {
            "type": "SECONDARY",
            "title": "pCR Rate",
            "denoms": [
              {
                "units": "Participants",
                "counts": [
                  {
                    "value": "1",
                    "groupId": "OG000"
                  },
                  {
                    "value": "2",
                    "groupId": "OG001"
                  }
                ]
              }
            ],
            "groups": [
              {
                "id": "OG000",
                "title": "HR Positive",
                "description": "patients that are hormone receptor (HR) positive (assessment at baseline)"
              },
              {
                "id": "OG001",
                "title": "HR Negative",
                "description": "Patients that are hormone receptor (HR) negative (assessed at baseline)"
              }
            ],
            "classes": [
              {
                "categories": [
                  {
                    "measurements": [
                      {
                        "value": "0",
                        "groupId": "OG000"
                      },
                      {
                        "value": "2",
                        "groupId": "OG001"
                      }
                    ]
                  }
                ]
              }
            ],
            "paramType": "COUNT_OF_PARTICIPANTS",
            "timeFrame": "pCR assessment was done following surgery after neoadjuvant therapy with paclitaxel and trastuzumzb&#x2F;pertuzumab prior to adjuvant therapy",
            "description": "rate of pathological complete response (pCR) between the treatment groups by HR status",
            "unitOfMeasure": "Participants",
            "reportingStatus": "POSTED",
            "populationDescription": "While total number of HR positive patients and HR negative patients in the overall treatment group is 2 and 3 respectively, only 1 patient in the former and 2 patients in the later group were evaluated for pCR at surgery"
          },
          {
            "type": "SECONDARY",
            "title": "Patient Reported Outcomes (Global Health Status)",
            "denoms": [
              {
                "units": "Participants",
                "counts": [
                  {
                    "value": "3",
                    "groupId": "OG000"
                  },
                  {
                    "value": "2",
                    "groupId": "OG001"
                  },
                  {
                    "value": "2",
                    "groupId": "OG002"
                  },
                  {
                    "value": "2",
                    "groupId": "OG003"
                  }
                ]
              }
            ],
            "groups": [
              {
                "id": "OG000",
                "title": "Patients Who Underwent Surgery (Assessment at Screening)",
                "description": "<p>Of the treatment population, those patients who underwent surgery post neoadjuvant therapy.</p><p>The assessment time period is at screening</p>"
              },
              {
                "id": "OG001",
                "title": "Patients Who Underwent Surgery (Assessment After Adjuvant Therapy)",
                "description": "<p>Of the treatment population, those patients who underwent surgery post neoadjuvant therapy.</p><p>The assessment time period is after adjuvant therapy</p>"
              },
              {
                "id": "OG002",
                "title": "Patients With Omission of Surgery (Assessment at Screening)",
                "description": "<p>Of the treatment population, those patients with omission of surgery post neoadjuvant therapy.</p><p>The assessment time period is at screening</p>"
              },
              {
                "id": "OG003",
                "title": "Patients With Omission of Surgery (Assessment After Adjuvant Therapy)",
                "description": "<p>Of the treatment population, those patients who underwent surgery post neoadjuvant therapy.</p><p>The assessment time period is after adjuvant therapy</p>"
              }
            ],
            "classes": [
              {
                "categories": [
                  {
                    "measurements": [
                      {
                        "value": "5",
                        "groupId": "OG000",
                        "lowerLimit": "5",
                        "upperLimit": "6"
                      },
                      {
                        "value": "4",
                        "groupId": "OG001",
                        "lowerLimit": "3.5",
                        "upperLimit": "4.5"
                      },
                      {
                        "value": "5.25",
                        "groupId": "OG002",
                        "lowerLimit": "4.5",
                        "upperLimit": "6"
                      },
                      {
                        "value": "5",
                        "groupId": "OG003",
                        "lowerLimit": "4",
                        "upperLimit": "6"
                      }
                    ]
                  }
                ]
              }
            ],
            "paramType": "MEDIAN",
            "timeFrame": "The questionnaire was filled by the patients at screening and post adjuvant therapy.",
            "description": "<p>The EORTC QLQ-C30 was used to assess Health-Related Quality of Life (QoL).\nThe measure consists of five functional scales (physical, role, cognitive, emotional, and social).\nFor this study, raw scores were used without any transformation.\nThe functional scales consist of multiple items (questions 1-28) scored on a 1-4 scale (1 = not at all, 4 = very much).\nHigher scores indicate worse functioning.\nTo assess the effect of standard therapy (surgery after neoadjuvant therapy) vs. investigational therapy (omission of surgery), the global health status is reported in each of these populations before and after treatment.</p><p>The Global Health Status (GHS) score is derived from two items (Q29 and Q30), each scored on a 1-7 scale (1 = very poor, 7 = excellent).</p><p>Scoring method: GHS = (Q29 + Q30) &#x2F; 2 Raw score range: Minimum = (1 + 1) &#x2F; 2 = 1; Maximum = (7 + 7) &#x2F;2 = 7</p>",
            "unitOfMeasure": "score on a scale",
            "dispersionType": "Full Range",
            "reportingStatus": "POSTED",
            "populationDescription": "Out of the treatment population, 3 patients underwent surgery post neoadjuvant therapy (standard therapy) and 2 patients did not undergo surgery (investigative therapy).\nAll the patients of both the groups completed the patient reported outcomes questionaire at screening. 1 patient from the patient group that underwent surgery did not complete the questionnaire after adjuvant therapy."
          }
        ]
      },
      "participantFlowModule": {
        "groups": [
          {
            "id": "FG000",
            "title": "Treatment Arm",
            "description": "<p>Treatment in women with primary operable HER2-positive, HER2-enriched(HER2-E)&#x2F;ERBB2-high breast cancer according to PAM50 intrinsic subtype and a ERBB2 pre-defined cutoff (high vs low ERBB2 expression):</p><ul><li>Tumor size ≤ 2 cm: Paclitaxel&#x2F;trastuzumab&#x2F;pertuzumab (TDM-1 if residual disease)</li><li>Tumor size &gt; 2 cm and ≤ 4cm: Antracycline based chemotherapy followed by Paclitaxel&#x2F;trastuzumab&#x2F;pertuzumab (TDM-1 if residual disease)</li></ul>"
          }
        ],
        "periods": [
          {
            "title": "Study treatment",
            "milestones": [
              {
                "type": "STARTED",
                "achievements": [
                  {
                    "groupId": "FG000",
                    "numSubjects": "5"
                  }
                ]
              },
              {
                "type": "COMPLETED",
                "achievements": [
                  {
                    "groupId": "FG000",
                    "numSubjects": "5"
                  }
                ]
              },
              {
                "type": "NOT COMPLETED",
                "achievements": [
                  {
                    "groupId": "FG000",
                    "numSubjects": "0"
                  }
                ]
              }
            ]
          },
          {
            "title": "Follow-up after 1 year",
            "milestones": [
              {
                "type": "STARTED",
                "achievements": [
                  {
                    "groupId": "FG000",
                    "numSubjects": "5"
                  }
                ]
              },
              {
                "type": "COMPLETED",
                "achievements": [
                  {
                    "groupId": "FG000",
                    "numSubjects": "4"
                  }
                ]
              },
              {
                "type": "NOT COMPLETED",
                "achievements": [
                  {
                    "groupId": "FG000",
                    "numSubjects": "1"
                  }
                ]
              }
            ],
            "dropWithdraws": [
              {
                "type": "Lost to Follow-up",
                "reasons": [
                  {
                    "groupId": "FG000",
                    "numSubjects": "1"
                  }
                ]
              }
            ]
          },
          {
            "title": "Follow up at 3 yrs",
            "milestones": [
              {
                "type": "STARTED",
                "achievements": [
                  {
                    "groupId": "FG000",
                    "numSubjects": "4"
                  }
                ]
              },
              {
                "type": "COMPLETED",
                "achievements": [
                  {
                    "groupId": "FG000",
                    "numSubjects": "0"
                  }
                ]
              },
              {
                "type": "NOT COMPLETED",
                "achievements": [
                  {
                    "groupId": "FG000",
                    "numSubjects": "4"
                  }
                ]
              }
            ]
          }
        ],
        "recruitmentDetails": "Overall, 20 patients were screened for the study in a single study centre (clinical setting) over the duration of 18 months.\nA total of 5 patients were finally selected for the study treatment after meeting all the inclusion criteria and signing the ICF",
        "preAssignmentDetails": "<p>Out of 20 patients screened, 13 patients did not fulfill the study criteria (PAM50 subtype other than HER2-Enriched, ERBB2 high, liver metastasis, multicentric tumor).</p><p>Finally only 5 patients that fulfilled all eligibility criteria and signed the ICF were included</p>"
      },
      "baselineCharacteristicsModule": {
        "denoms": [
          {
            "units": "Participants",
            "counts": [
              {
                "value": "5",
                "groupId": "BG000"
              }
            ]
          }
        ],
        "groups": [
          {
            "id": "BG000",
            "title": "Treatment Arm",
            "description": "<p>Treatment in women with primary operable HER2-positive, HER2-enriched(HER2-E)&#x2F;ERBB2-high breast cancer according to PAM50 intrinsic subtype and a ERBB2 pre-defined cutoff (high vs low ERBB2 expression):</p><ul><li>Tumor size ≤ 2 cm: Paclitaxel&#x2F;trastuzumab&#x2F;pertuzumab (TDM-1 if residual disease)</li><li>Tumor size &gt; 2 cm and ≤ 4cm: Antracycline based chemotherapy followed by Paclitaxel&#x2F;trastuzumab&#x2F;pertuzumab (TDM-1 if residual disease)</li></ul>"
          }
        ],
        "measures": [
          {
            "title": "Age, Customized",
            "classes": [
              {
                "title": "&gt;= 40 yrs",
                "categories": [
                  {
                    "measurements": [
                      {
                        "value": "5",
                        "groupId": "BG000"
                      }
                    ]
                  }
                ]
              }
            ],
            "paramType": "NUMBER",
            "unitOfMeasure": "participants"
          },
          {
            "title": "Sex: Female, Male",
            "classes": [
              {
                "categories": [
                  {
                    "title": "Female",
                    "measurements": [
                      {
                        "value": "5",
                        "groupId": "BG000"
                      }
                    ]
                  },
                  {
                    "title": "Male",
                    "measurements": [
                      {
                        "value": "0",
                        "groupId": "BG000"
                      }
                    ]
                  }
                ]
              }
            ],
            "paramType": "COUNT_OF_PARTICIPANTS",
            "unitOfMeasure": "Participants"
          },
          {
            "title": "Race&#x2F;Ethnicity, Customized",
            "classes": [
              {
                "title": "Caucasian",
                "categories": [
                  {
                    "measurements": [
                      {
                        "value": "5",
                        "groupId": "BG000"
                      }
                    ]
                  }
                ]
              }
            ],
            "paramType": "NUMBER",
            "unitOfMeasure": "participants"
          },
          {
            "title": "Region of Enrollment",
            "classes": [
              {
                "title": "Spain",
                "categories": [
                  {
                    "measurements": [
                      {
                        "value": "5",
                        "groupId": "BG000"
                      }
                    ]
                  }
                ]
              }
            ],
            "paramType": "NUMBER",
            "unitOfMeasure": "participants"
          },
          {
            "title": "Menopausal Status",
            "classes": [
              {
                "title": "Postmenopausal (min 12 mnths without menses before neoadyuvance treatment)",
                "categories": [
                  {
                    "measurements": [
                      {
                        "value": "4",
                        "groupId": "BG000"
                      }
                    ]
                  }
                ]
              },
              {
                "title": "premenopausal",
                "categories": [
                  {
                    "measurements": [
                      {
                        "value": "1",
                        "groupId": "BG000"
                      }
                    ]
                  }
                ]
              }
            ],
            "paramType": "NUMBER",
            "unitOfMeasure": "participants"
          },
          {
            "title": "ECOG baseline",
            "classes": [
              {
                "title": "Grade 0",
                "categories": [
                  {
                    "measurements": [
                      {
                        "value": "4",
                        "groupId": "BG000"
                      }
                    ]
                  }
                ]
              },
              {
                "title": "Grade 1",
                "categories": [
                  {
                    "measurements": [
                      {
                        "value": "1",
                        "groupId": "BG000"
                      }
                    ]
                  }
                ]
              }
            ],
            "paramType": "NUMBER",
            "description": "Scale: Grades 0-4 Grade 0 - Fully active able to carry on all pre-disease performance without restriction; Grade 1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature e.g.\nlight house work office work; Grade 2 - Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours Grade 3 - Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours Grade 4 - Completely disabled; cannot carry on any selfcare; totally confined to bed or chair",
            "unitOfMeasure": "participants"
          },
          {
            "title": "Previous cancer history",
            "classes": [
              {
                "title": "Yes",
                "categories": [
                  {
                    "measurements": [
                      {
                        "value": "0",
                        "groupId": "BG000"
                      }
                    ]
                  }
                ]
              },
              {
                "title": "No",
                "categories": [
                  {
                    "measurements": [
                      {
                        "value": "5",
                        "groupId": "BG000"
                      }
                    ]
                  }
                ]
              }
            ],
            "paramType": "NUMBER",
            "unitOfMeasure": "participants"
          }
        ],
        "populationDescription": "The baseline analysis population is the same as the treatment population"
      }
    }
  },
  {
    "op": "add",
    "path": "/documentSection",
    "value": {
      "largeDocumentModule": {
        "largeDocs": [
          {
            "date": "2019-10-17",
            "size": 4292401,
            "label": "Study Protocol and Statistical Analysis Plan",
            "hasIcf": false,
            "hasSap": true,
            "filename": "Prot_SAP_000.pdf",
            "typeAbbrev": "Prot_SAP",
            "uploadDate": "2025-09-03T04:05",
            "hasProtocol": true
          }
        ]
      }
    }
  }
]