Factors Influencing Breast Cancer Resection Volumes And Their Impact on Treatment Outcome (FIBRATIO) — FIBRATIO  

Breast Cancer Clinical Trial

Official title: Factors Influencing Breast Cancer Resection Volumes And Their Impact on Treatment Outcome: a Prospective Multicenter Study (FIBRATIO)

Status Active, not recruiting

Clinical Trial Summary

The number of breast cancer survivors is constantly growing. Breast conserving surgery (BCS) is equal or superior to mastectomy both regarding survival and quality of life (QoL). Hence, as many patients as possible should be treated using BCS. The results indicate that the rate of mastectomies in Finland is higher than in Europe, while the rate of reoperations due to insufficient margins after BCS is lower in Finland than globally. With this study we aim to identify the optimal balance of radicality and tissue-conservation in BCS.

The aim of this study is to measure the volume of the resected breast tissue and the width of the healthy tissue margins and to compare these with the radiological and histological tumor size and with the size of the breast and their correlation with theoretically optimal and excised volumes.

This is a national prospective multicenter study conducted in five breast units. 250 women with primary, unilateral, cTis-T2 breast cancer eligible for BCS will be recruited. The diagnostics and treatment of the patients will be carried out following the Finnish national guideline. The size of the breast and the radiological size of the tumor will be measured preoperatively using mammograms and MRI. The histological tumor volume and the resection volume will be measured postoperatively. The optimal resection volume is calculated as the difference of the total resection volume and the volume of the tumor with an added 1 cm margin.

To map the impact of the treatment on QoL and body image, the patients are surveyed using EORTC-QLQ-C30 and BREAST-Q Breast Conserving Therapy Module QoL questionnaires preoperatively, 3-8 weeks postoperatively, and two years after the radiotherapy. Objective evaluation of the aesthetic outcome is assessed by the BCCT.core software that uses medical photographs taken at the same time points as the questionnaires are filled.

Clinical Trial Description

1. Background

Breast cancer is the most common cancer worldwide. The prognosis of early-stage breast cancer is good - more than 90 % of the patients are alive five years after diagnosis. Since many patients live decades after the diagnosis, besides oncological outcome, aesthetic, and functional outcomes are important for patients as a factor of quality of life (QoL) and global health. Breast conserving surgery (BCS) is equal or superior to mastectomy (Mx) both regarding survival and quality of life (QoL). Even if a patient has had immediate breast reconstruction their body image is inferior after mastectomy compared to those undergoing BCS.

The aim of BCS is to remove the tumor with histologically negative margins defined as no ink on tumor for invasive carcinoma and 2 mm histological margin for ductal carcinoma in situ (DCIS). Wider negative margins do not improve local control when BCS is combined with radiotherapy (RT) but predispose patients to larger excision volumes and inferior cosmetic outcomes. Contrastingly, more conservative resections are associated with positive histological margins, which double the risk of tumor recurrence. Therefore, re-operation is performed for positive histological margins. Rates of re-excision vary widely between surgeons and facilities and according to recent international studies are up to 30 %. Re-operation is associated with several adverse outcomes such as delayed adjuvant treatment and impaired cosmetic outcomes and QoL.

Finding the right balance between BCS and mastectomies, and the optimization of resection volumes are important considerations for surgical care of breast cancer. BCS rate and reoperation rate are both quality indicators of the European Society of Breast Cancer Specialists. The rate of mastectomies for early breast cancer in certified European breast units is approximately 25 %. There is no exact data on the rate of Mxs according to progression for Finland, however, it appears to be higher than in European units. Contrastingly, 8-13 % of the patients having BCS require a reoperation due to positive histological margins in Finland. These findings raise the question whether more BCS could be performed and with smaller macroscopic margins.

Since the variation in reoperation rates, rates of mastectomies and resection volumes is largely unexplained, more research is needed to identify the root causes to enable effective interventions and raise the standards of care. Tumors and their anatomical location in the breast, breasts of the patients and surgical techniques vary and therefore measuring the BCS is challenging. Additionally, long-term cosmetic and functional outcomes are confounded by the effect of radiotherapy, and final outcome can be observed no earlier than two years after operation. In practice, measuring the ratio of the tumor volume to resection volume could provide comparable data and could even be a quality indicator of BCS. Our team has previously studied the technological innovations for intraoperative margin assessment and conducted retrospective analysis on the breast cancer margins in Finland. To effectively assess the factors affecting the resection volumes and obtained margins, a prospective approach is needed. A multicenter approach gives a comprehensive look on variation between institutions and surgeons. A study of this nature has not been conducted before.

2. Aim of the study

The aim of this study is to measure the volume of the resected breast tissue and the width of the healthy tissue margins and to compare these with the radiological and histological tumor size and with the size of the breast and their correlation with theoretically optimal and excised volumes. These results help breast surgeons to find optimal balance of radicality and tissue-conservation.

Primary endpoints

• What is the effect of breast-related QoL and objective aesthetic outcome, as measured with BCCT.core, of the treatment on patient's overall QoL?

• Are there differences in resection volumes and patient-related outcomes between surgeons or breast centers?

• The ratio of theoretically optimal and excised resection volume for the tumor

Secondary endpoints

• What is the effect of radiotherapy on breast volume and shape?

• What is the effect of the preoperative multidisciplinary team (MDT) treatment plan on the results?

• What is the reoperation rate due to positive histological margins?

• What is the effect of the tumor subtype, tumor size, DCIS component, tumor palpability or preoperative MRI imaging on the resection margins?

3. Research methods and execution

3.1 Trial design and participants

This is a national prospective multicenter study with a sample of 250 patients. The inclusion criterion is primary, unilateral cTis-T2 breast cancer eligible for BCS. Both conventional and volume-displacement oncoplastic techniques can be applied as long as the procedure is unilateral. The patients will be recruited from five Finnish breast units. For one surgeon at least 20 procedures are required. The sample size is powered to detect differences between centres and individual surgeons (alfa=0.05, beta=0.2, effect size 0.3) with the presumed loss of a maximum of 20% of patients at 2-year follow-up in terms of primary endpoints.

Exclusion criteria for the study are metastatic, bilateral, and hereditary breast cancers or earlier breast cancer of the same or contralateral breast. Also, a symmetrisation procedure of the healthy breast simultaneously with the cancer operation or earlier breast procedures (excluding bilateral reduction mammoplasty/mastopexy) are contraindications. If the patient is not eligible for radiotherapy, has received neoadjuvant treatment, is pregnant or breastfeeding or is unable to provide an informed consent, she is not included in the study.

For all patients the following data will be collected: age, BMI, comorbidity, smoking status, hormonal status, radiological data of the patient's breasts and the tumor, preoperative MDT data, histopathological data on the tumor and the margins, details of the operative treatment, postoperative complications, and details of the oncologic treatments.

For all breast units the following characteristics will be collected: annual number of new primary breast cancers and primary breast cancer operations, Mx-rate, number of immediate and delayed breast reconstructions, number of surgeons, information about MDT principles For all breast surgeons the following characteristics will be collected: age, gender, specialty, years of work experience and workplace The diagnostics and treatment of the patients will be carried out following the Finnish national guideline, which is in line with international guidelines. The patients will not undergo any additional laboratory tests or imaging. The data will be collected from examinations done routinely during the diagnostic phase and follow-up phase.

3.2 Volumetric measurements and the resection ratio

The breast volume is calculated preoperatively and after radiotherapy by using mammography measurements (breast height, breast width and compression thickness) and the preoperative tumor volume by mammography and/or by the MRI. The effect of radiotherapy on breast size is calculated by comparing the preoperative and postoperative volume of the breast while considering the resection volume.

The fresh surgical specimen is submerged in saline and its volume is measured using calculations based on Archimedes principle and Newton's third law. The radiological and histological tumor volume is calculated assuming the tumor to resemble an obloid spheroid.

Optimal resection volume (ORV) is defined as the spherical volume of the tumor with an added 1.0 cm margin of healthy breast tissue. Total resection volume (TRV) is the measured volume of the fresh surgical specimen. TRV is compared to ORV to determine the excess of breast tissue resection (TRV/ORV=CRR) defined as calculated resection rate (CRR). Optimal CCR is 1.0.

3.3 Quality of life and aesthetic results

To map the impact of the treatment on QoL and body image, the patients are photographed and surveyed using QoL questionnaires (EORTC-QLQ-C30 version 3.0 and BREAST-Q Version 2.0 Breast Conserving Therapy Module) preoperatively, 3-8 weeks postoperatively and two years after the radiotherapy. Objective evaluation of the aesthetic outcome is assessed by the 'BCCT.core software' - INESC Porto Breast Research group based on medical photographs. The photographs are taken at same time points as QoL questionnaires are filled.

The tumor-to-TRV ratios are analyzed between surgeons and centers while controlling for potential confounders at 3-8 weeks after surgery. Additionally, the correlation of the factors with aesthetic and QoL measures is analyzed at 3-8 weeks after surgery and 2 years after RT when the effect of radiation and adjuvant therapies is also fully included.

4. Schedule

The trial inclusion will begin in the spring 2022. Before the inclusion we will do a pilot study of five patients to validate the measuring techniques, the QoL questionnaires and the BCCT.core program.

The results will be analyzed at two time points:

1. 3-8 weeks after the operation

2. two years after the radiotherapy

The final results of the study should be available during 2025. The results will be published in peer-reviewed journals of surgical oncology. ;

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Multidisciplinary Communication
• Patient Satisfaction
• Quality of Life
• Resection Margin

• NCT number: NCT05257577
• Study type: Observational [Patient Registry]
• Source: Tampere University Hospital
• Status: Active, not recruiting
• Start date: May 28, 2022
• Completion date: March 30, 2027