Dataset Information

A Randomized Controlled Trial for Doing vs. Omitting Intraoperative Frozen Section Biopsy for Resection Margin Status in Selected Patients Undergoing Breast-Conserving Surgery (OFF-MAP Trial).

ABSTRACT:

Purpose

Intraoperative frozen section biopsy is used to reduce the margin positive rate and re-excision rate and has been reported to have high diagnostic accuracy. A majority of breast surgeons in the Republic of Korea routinely perform frozen section biopsy to assess margins intraoperatively, despite its long turnaround time and high resource requirements. This study aims to determine whether omitting frozen section biopsy for intraoperative margin evaluation in selected patients is non-inferior to performing frozen section biopsy in terms of resection margin positivity rate.

Methods

This study is a phase III, randomized controlled, parallel-group, multicenter non-inferiority clinical trial. Patients meeting the inclusion criteria and providing written informed consent will be randomized to the "frozen section biopsy" or "frozen section biopsy omission" group after lumpectomy. Patients with clinical stage T1-T3 disease who are diagnosed with invasive breast cancer by core-needle biopsy and plan to undergo breast-conserving surgery will be included in this study. If a daughter nodule, non-mass enhancement, or microcalcification is identified on preoperative imaging, these features must be within 1 cm of the main mass for inclusion in the trial. The target sample size is 646 patients per arm. The primary endpoint will be the resection margin positive rate, and the secondary endpoints include the reoperation rate, operating time, residual cancer after reoperation, residual cancer after re-excision according to the frozen section biopsy result, resection volume, patient quality of life, and cost-effectiveness.

Discussion

This is the first randomized clinical trial utilizing frozen section biopsy for intraoperative margin evaluation and aims to determine the non-inferiority of omitting frozen section biopsy in selected patients compared to performing frozen section biopsy. We expect that this trial will help surgeons perform the procedure more efficiently while ensuring patient safety.

Trial registration

ClinicalTrials.gov Identifier: NCT03975179; Clinical Research Information Service Identifier: KCT0004606.

SUBMITTER: Yoo TK

PROVIDER: S-EPMC8724377 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Intraoperative frozen-section analysis of the lumpect-omy margin during breast-conserving surgery (BCS) is an excellent method in obtaining a clear resection margin. This study aimed to investigate the usefulness of intraoperative circumferential frozen-section analysis (IOCFS) of lumpectomy margin during BCS for breast cancer, and to find factors that increase the conversion into mastectomy.From 2007 to 2011, 509 patients with breast cancer underwent IOCFS during BCS. The outer surfaces of the shaved lumpectomy margins were evaluated. A negative margin was defined as no ink on the tumor. All margins were evaluated using the permanent section analysis.Among the 509 patients, 437 (85.9%) underwent BCS and 72 (14.1%) finally underwent mastectomy. Of the 483 pathologically confirmed patients, 338 (70.0%) were true-negative, 24 (5.0%) false-negative, 120 (24.8%) true-positive, and 1 (0.2%) false-positive. Twenty-four patients (4.7%) among total 509 patients had undetermined margins as either atypical ductal hyperplasia or ductal carcinoma in situ in the first IOCFS. The IOCFS has an accuracy of 94.8% with 83% sensitivity, 99.7% specificity, 93.4% negative predictive value, and 99.2% positive predictive value. Sixty-three cases (12.4%) were converted to mastectomy, the first intraoperatively. Of the 446 (87.6%) patients who successfully underwent BCS, 64 patients received additional excisions and 32 were reoperated to achieve clear margin (reoperation rate, 6.3%). Twenty-three of the reoperated patients underwent re-excisions using the second intraoperative frozen section analysis, and achieved BCS. Nine cases were additionally converted to mastectomy. No significant differences in age, stage, and biological factors were found between the BCS and mastectomy cases. Factors such as invasive lobular carcinoma, multiple tumors, large tumor, and multiple excisions increased the conversion to mastectomy.The IOCFS analysis during BCS is useful in evaluating lumpectomy margins and preventing reoperation.

Project description:ImportanceComplete (R0) resection is the dominant prognostic factor for survival across solid tumor types. Achieving adequate tumor clearance with appropriate margins is particularly difficult in nonpalpable tumors or in situ disease. Previous methods to address this problem have proven time consumptive, impractical, or ineffective.ObjectiveTo assess the capability of intraoperative molecular imaging (IMI), a novel technology using a fluorescent tracer targeted to malignant cells, to localize visually occult, nonpalpable tumors and quantify margin distances during resection.Design, setting, and participantsThis nonrandomized open-label trial of IMI using a folate receptor-targeted fluorescent tracer enrolled patients between May 2017 and June 2020 at a single referral center. Eligible patients included those with a small (T1) lung lesion suspicious for malignant neoplasms and with radiographic features suggestive of a nonpalpable lesion.InterventionsPatients were preoperatively infused with a folate receptor-targeted near-infrared tracer. Intraoperatively, surgeons used thoracoscopic visualization and palpation to identify lesions. IMI was performed to detect the lesion in situ, and lesions were imaged ex vivo. Margins were assessed by IMI before comparison with those reported on final histopathologic analysis.Main outcomes and measuresThe main outcomes were whether IMI could (1) localize nonpalpable lung lesions in situ and (2) quantify margin distance with comparison with final pathology as the criterion standard. Patient demographic information and lesion characteristics were prospectively recorded.ResultsOf 40 patients, 26 (65%) were female, and the median (interquartile range) age was 66.5 (62-72) years. Conventional surgical methods localized 22 of 40 lesions (55%), while IMI localized 36 of 40 (90%). Of 18 nonpalpable lesions, 15 (83.3%) were identified by IMI. Both palpable and nonpalpable lesions demonstrated mean signal-to-background ratio more than 2. An IMI margin was able to be calculated for 39 of 40 patients (95%). IMI margins were nearly identical to margins reported on final pathology (R2 = 0.9593), with median (interquartile range) difference of 1.3 (0.7-2.0) mm. IMI detected 2 margins in nonpalpable tumors that were clinically unacceptable and would have had a high probability of recurrence.Conclusions and relevanceTo our knowledge, this study presents the first clinical use of IMI for nonpalpable tumors and provides proof of principle for the utility of IMI across the field of surgical oncology in identifying occult disease and tumor-positive margins.