HISMAR: Intraoperative Margin Assessment Using the Histolog® Scanner to Reduce Reoperation in Breast-Conserving Surgery (HISMAR)

HISMAR: A Prospective Post-Market Performance Follow-up Study of the Histolog Scanner for Intraoperative Margin Assessment in Breast-Conserving Surgery for High-Risk Histological Subtypes (ILC, DCIS, NST+DCIS)

This study evaluates whether systematic intraoperative margin assessment using the Histolog® Scanner - a confocal fluorescence microscopy device - reduces the need for reoperation after breast-conserving surgery (lumpectomy) in women with lobular carcinoma (ILC), ductal carcinoma in situ (DCIS), or invasive carcinoma with a DCIS component (NST+DCIS).

After lumpectomy, the fresh specimen is imaged in real time by the surgeon using the Histolog® Scanner, which produces histological-quality images of the specimen surface without any tissue processing. This allows immediate assessment of surgical margins in the operating room, enabling the surgeon to perform additional tissue removal if needed before closing.

Based on institutional data from 266 cases at CHVR (2021-2024), the current reoperation rate in this population is 11.3%. The study tests whether systematic use of the Histolog® Scanner in addition to standard care reduces this rate by 50% or more (to ≤5.6%). A total of 228 patients will be enrolled prospectively at the Centre Hospitalier du Valais Romand (CHVR), Sion, Switzerland. The reoperation decision is made by the multidisciplinary tumour board based on final histopathology results, independently of the intraoperative findings.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer; Breast Neoplasm Female; Ductal Carcinoma In Situ; Invasive Lobular Carcinoma
• Intervention / Treatment: Device: Histolog® Scanner

Detailed Description

BACKGROUND Breast cancer is the most common cancer in women in Switzerland, with approximately 6,500 new cases annually. Breast-conserving surgery (BCS, lumpectomy) is the preferred surgical approach for localised tumours and achieves equivalent survival outcomes to mastectomy when negative margins are obtained. However, re-excision rates of 20-30% have been reported in unselected BCS populations.

The risk of positive margins is particularly elevated in specific histological subtypes: published data indicate a relative risk of positive margins of 2.21 for ductal carcinoma in situ (DCIS) and 1.44 for invasive lobular carcinoma (ILC) compared to NST carcinoma without in situ component. A retrospective analysis of 266 consecutive eligible BCS cases at CHVR (2021-2024) identified a reoperation rate of 11.3% (30/266). A prospective study in the literature reported a reduction from 30% to 10% when intraoperative histological scanning was added to standard of care.

DEVICE The Histolog® Scanner (SamanTree Medical SA, Lausanne; CE IVD Class A, UDI 764017998003GV, software v3.4.0) enables real-time confocal fluorescence imaging of fresh lumpectomy specimen surfaces ex vivo, without tissue processing or staining, providing H&E-quality images intraoperatively. The device is already in routine clinical use at CHVR.

STUDY OBJECTIVE To evaluate whether systematic use of the Histolog® Scanner in addition to standard of care reduces the reoperation rate by 50% or more - from 11.3% to ≤5.6% - in patients with ILC, pure DCIS, or NST+DCIS undergoing BCS at CHVR.

STUDY DESIGN Prospective, single-arm, single-centre post-market performance follow-up (PMPF) study (IVDR 2017/746). Comparator: validated historical institutional control (CHVR 2021-2024, same surgical team, n=266, reoperation rate 11.3%). A randomised design was not ethically justifiable as the device is already in routine use at CHVR.

PROCEDURE Following lumpectomy, the fresh specimen undergoes standard palpation then systematic Histolog® Scanner imaging (ex vivo, on the specimen surface). At the surgeon's discretion, standard radiological assessment is also performed. Intraoperative recuts are decided based on combined standard of care and Histolog® Scanner findings. The specimen is sent to the institutional pathology laboratory (ICH-CHVR) for definitive histopathology. The primary endpoint (reoperation recommendation) is determined by the multidisciplinary tumour board based on final histopathology, independently of intraoperative findings.

OUTCOMES Primary: reoperation rate (proportion of patients for whom the tumour board recommends re-excision), assessed within 4 weeks of BCS.

Secondary: (1) subgroup reoperation rates (ILC, pure DCIS, NST+DCIS); (2) intraoperative recut rate and localisation; (3) cost analysis; (4) exploratory concordance between intraoperative and final pathological margin status.

ELIGIBILITY Inclusion: women ≥18 years; CNB/VAB confirming ILC, pure DCIS, or NST+DCIS; planned BCS at CHVR; signed eIC.

Exclusion: pregnancy; prior neo-adjuvant treatment; mastectomy indication; acriflavine hypersensitivity; incapacity to consent.

SAMPLE SIZE n=228 patients (205 evaluable minimum; 10% dropout). Calculated by one-sample z-test (Fleiss 1981): α=0.05 two-sided, power=80%, p₀=11.3%, p₁=5.6%. Estimated recruitment: 3-3.5 years.

STATISTICAL ANALYSIS Primary: one-sample z-test for a proportion (two-sided, α=0.05), per-protocol population, with exact 95% Clopper-Pearson CI. Pass criterion: p<0.05 and observed rate ≤5.6%. Sensitivity analysis on ITT population. No interim analysis planned.

ETHICAL / REGULATORY Category A1 (ClinO-MD Art. 6a). CEC: Commission cantonale d'éthique du Valais (CCVS). No Swissmedic approval required. Electronic informed consent (eIC). Declared conflict of interest: PI holds a consultancy arrangement with SamanTree Medical SA (institutional fee); mitigation: independent tumour board endpoint, independent biostatistician.

FUNDING Institutional budget of CHVR. No industry funding.

• Study Type: Interventional
• Enrollment (Estimated): 228
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Colin Simonson, MD; Phone Number: +41276038331; Email: Colin.simonson@hopitalvs.ch
• Study Contact Backup: Name: Daniela Huber, Prof. MD; Email: DanielaEmanuela.Huber@hopitalvs.ch

Study Locations

• Switzerland
  • Valais
    • Sion, Valais, Switzerland, 1950
      • Centre Hospitalier du Valais Romand (CHVR)
      • Principal Investigator: Colin Simonson, MD
      • Contact: Colin Simonson, MD; Phone Number: +41276038331; Email: Colin.simonson@hopitalvs.ch
      • Contact: Daniela Huber, Prof. MD; Email: DanielaEmanuela.Huber@hopitalvs.ch
      • Sub-Investigator: Daniela Huber, Prof.MD
      • Sub-Investigator: Régine Lachat, MD
      • Sub-Investigator: Stephanie Seidler, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

1. Female patient, aged 18 years or older at time of surgery.

2. Pre-operative core needle biopsy (CNB) or vacuum-assisted biopsy (VAB) with histological diagnosis of one of the following:

   1. invasive lobular carcinoma (ILC/CLI),
   2. pure ductal carcinoma in situ (DCIS), or
   3. invasive carcinoma of non-special type (NST) with an associated DCIS component.
3. Planned breast-conserving surgery (BCS / lumpectomy) at CHVR.
4. Signed electronic informed consent (eIC) obtained prior to any study procedure.

Exclusion Criteria:

1. Pregnancy (confirmed or suspected) at time of surgery.
2. Prior neo-adjuvant treatment (hormonal therapy or chemotherapy) for the current breast cancer diagnosis.
3. Surgical indication for mastectomy rather than BCS.
4. Known hypersensitivity or allergy to acriflavine (fluorescent staining agent used with the Histolog Scanner).
5. Incapacity to provide informed consent.
6. Previous enrolment in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Histolog® Scanner + Standard of Care; Patients undergo breast-conserving surgery (BCS) with systematic intraoperative margin assessment using the Histolog® Scanner in addition to standard of care (palpation, specimen radiography at surgeon's discretion). Intraoperative recuts are decided based on combined standard of care and Histolog® Scanner findings. The reoperation decision is made by the multidisciplinary tumour board based on final histopathology, independently of intraoperative findings.

Device: Histolog® Scanner; CE-marked Class A IVD confocal fluorescence microscopy device (SamanTree Medical SA, Lausanne, Switzerland; UDI 764017998003GV; software v3.4.0). Used intraoperatively to image the surface of the fresh lumpectomy specimen ex vivo, without tissue processing or staining, providing real-time histological-quality margin assessment. Accessories: Histolog Dish (UDI 764017998004GX) and Histolog Dip fluorescent staining solution (UDI 764017998005GZ).; Other Names: Histolog Scanner

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reoperation Rate	Proportion of enrolled patients for whom the multidisciplinary tumour board recommends re-excision surgery following definitive histopathological analysis of the lumpectomy specimen. The outcome is binary (reoperation: yes/no). Compared against the historical institutional control rate of 11.3% (CHVR 2021-2024, n=266).	Within 4 weeks after breast-conserving surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reoperation rate	Proportion of patients requiring reoperation within each histological subgroup: (1) invasive lobular carcinoma (ILC), (2) pure ductal carcinoma in situ (DCIS), (3) invasive NST carcinoma with DCIS component (NST+DCIS).	Within 4 weeks after breast-conserving surgery
Intraoperative recut rate	Proportion of cases requiring at least one intraoperative recut, with distinction between recuts indicated by standard of care versus recuts additionally indicated by Histolog Scanner findings. Localisation recorded (cranial, medial, caudal, lateral).	Intraoperative
Cost analysis	Estimated cost differential between the prospective study group and the historical control group, accounting for the cost of reoperations avoided and the cost of Histolog Scanner use per procedure.	At study completion, approximately 3.5 years
Concordance between intraoperative and final pathological margin assessment	Exploratory analysis of sensitivity and specificity of intraoperative Histolog Scanner margin assessment versus definitive histopathological margin status, where data are available for at least 80% of cases.	Within 4 weeks after breast-conserving surgery

Collaborators and Investigators

• Sponsor: Hôpital du Valais
• Collaborators: SamanTree Medical SA
• Investigators: Principal Investigator: Colin Simonson, MD, Centre Hospitalier du Valais Romand (CHVR)

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: April 7, 2026
• First Submitted That Met QC Criteria: April 7, 2026
• First Posted (Actual): April 14, 2026

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: reoperation; confocal microscopy; DCIS; ILC; surgical margins; breast-conserving surgery; lumpectomy; intraoperative imaging; re-excision; histological scanning; post-market performance follow-up; PMPF
• Additional Relevant MeSH Terms: Breast Carcinoma In Situ; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Skin Diseases; Breast Diseases; Carcinoma; Neoplasms, Ductal, Lobular, and Medullary; Carcinoma in Situ; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Morphological and Microscopic Findings; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Lobular; Margins of Excision
• Other Study ID Numbers: HISMAR-CHVR-2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This is a single-centre post-market performance follow-up (PMPF) study with a limited sample size (n=228). No individual participant data (IPD) sharing is planned. Aggregate results will be published in a peer-reviewed journal and reported in ClinicalTrials.gov and BASEC upon study completion.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No