Delayed-immediate Versus Delayed Breast Reconstruction in Breast Cancer Patients With Mastectomy and Radiation Therapy

• ClinicalTrials.gov Identifier: NCT03730922
• Recruitment Status: Recruiting
• First Posted: November 5, 2018
• Last Update Posted: February 15, 2023
• Sponsor: Danish Breast Cancer Cooperative Group
• Information provided by (Responsible Party): Tove Filtenborg Tvedskov, Danish Breast Cancer Cooperative Group

Study Description

Brief Summary:

In breast cancer patients treated by mastectomy and adjuvant post-mastectomy radiation therapy (PMRT) reconstruction is often delayed until 6 - 12 month after completion of chemotherapy and PMRT, due to high risk of complication. In this trial the safety of the delayed-immediate reconstruction method is tested, where a skin sparing mastectomy and reconstruction with silicone implant is performed at primary surgery to save the native skin for the final delayed reconstruction.

Condition or disease	Intervention/treatment	Phase
Breast Neoplasm Female; Complication of Radiation Therapy; Breast Implant; Complications	Procedure: Delayed-immediate reconstruction; Procedure: Delayed reconstruction	Not Applicable

Detailed Description:

An increasing proportion of breast cancer patients treated by mastectomy wish for a breast reconstruction. If post-mastectomy radiation therapy is recommended, the reconstruction is often delayed until 6 - 12 months after completion of chemotherapy and radiation therapy due to risk of complication that might delay adjuvant treatment. At this time the native skin over the removed breast cannot be used in the reconstruction, resulting in a suboptimal aesthetic outcome. In the delayed-immediate reconstruction method, a skin sparing mastectomy and reconstruction with implant is performed at primary surgery, to save the native skin under radiation therapy, thereby improving the chance for a good aesthetic outcome at the final delayed reconstruction. In this trial breast cancer patients treated by mastectomy and loco-regional radiation therapy is randomized to either delayed reconstruction or delayed-immediate reconstruction. The complication rate as well as morbidity, aesthetic outcome and psychological well-being after delayed-immediate reconstruction will be compared with delayed reconstruction

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 590 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The DBCG RT Recon Trial: Delayed-immediate Versus Delayed Breast Reconstruction in Early Breast Cancer Patients Treated With Mastectomy and Adjuvant Loco-regional Radiation Therapy. A Multicenter Randomized Clinical Trial
• Actual Study Start Date: January 1, 2020
• Estimated Primary Completion Date: November 2023
• Estimated Study Completion Date: November 2033

Arms and Interventions

Arm	Intervention/treatment
Experimental: A: Delayed-immediate reconstruction; Primary Surgery: Skin sparing mastectomy (nipple sparing if appropriate) and axillary surgery according to guidelines or protocol. Reconstruction with silicone implant or expander covered by pectoral muscle and mesh or matrix. Delayed reconstruction: Final reconstruction with any reconstructive procedure - being it autologous or implant-based (one- or two-stage, +/- acellular dermal matrix (ADM)) - is performed 6-12 months after completion of chemotherapy and PMRT. Any contralateral procedure is allowed when doing the delayed surgery, but not in relation to the initial cancer surgery.	Procedure: Delayed-immediate reconstruction; Skin sparing mastectomy and reconstruction with silicone implant or expander covered by pectoral muscle and mesh or matrix. Final reconstruction with any reconstructive procedure 6-12 months after completion of chemotherapy and RT.
Active Comparator: B: Delayed reconstruction; Primary surgery: Total mastectomy and axillary surgery according to guidelines or protocol. Delayed reconstruction: 6-12 months after completion of PMRT: final recon-struction with any reconstructive procedure - being it autologous or implant-based (one-or two-stage, +/- ADM). Any contralateral procedure is allowed at any time point after PMRT has been delivered	Procedure: Delayed reconstruction; Total mastectomy and delayed reconstruction:with any reconstructive procedure 6-12 months after completion of PMRT

Outcome Measures

Primary Outcome Measures :

1. Number of patients with complications with surgical intervention [ Time Frame: 1 year after final reconstruction ]

   Number of patients with complication deeming surgical intervention necessary (excluding percutaneous drainage and antibiotic treatment for inflammation in cases without need for open drainage):

   • Infection
   • Hematoma
   • Loss of implant/expander
   • Necrosis
   • Seroma

Secondary Outcome Measures :

1. Number of patients with complications without surgical intervention [ Time Frame: 1 year after final reconstruction ]
   Number of patients with complication (Infection with need for antibiotics and/or necrosis) without intervention necessary
2. Depression [ Time Frame: 10 years post-final reconstruction ]
   Degree of Depression measured by Becks Depression Inventory, BDII using a scale from 1 to 4, 4 being the worst
3. Fear of cancer recurrence [ Time Frame: 10 years post-final reconstruction ]
   Fear of cancer recurrence measured by Concerns About Recurrence Questionnaire-3 (CARQ-3 ) on a scale from 1 to 10, 10 worst (fear all the time)
4. Patient´s satisfaction and quality of life (QoL) [ Time Frame: 10 years post-final reconstruction ]
   Patient satisfaction and QoL measures by the BREAST-Q-instruments on a scale from 1 to 5, 5 being worst
5. Timely initiation of adjuvant therapy [ Time Frame: 1 year ]
   Time from primary surgery to start of adjuvant therapy
6. Degree of patient reported morbidity regarding body image, painsensory disturbanses and feeling og lymphoedema [ Time Frame: 10 years post-final reconstruction ]
   Patient reported morbidity measured by a questionnaire. The prevalence of pain will be assessed on a 0-10 numerical rating scale (NRS) and reported as: 'light pain' NRS 1-3; 'moderate pain' NRS 4-6; and 'severe pain' NRS 7-10. Sensory disturbances will be assessed by a dichotomous 'yes/no' question,. Lymphoedema will be assessed on a 0-10 numerical rating scale, 10 being worst. Body image will be assessed on a 0-7 numerical rating scale, 7 being best.
7. Number of patients with lymphoedema [ Time Frame: 10 years post-final reconstruction ]
   Difference in arm circumference between arms 15 cm/10 cm proximal/distal to the olecranon bilaterally. Any difference ≥10% defines lymhoedema.
8. Number of patients with restricted range of motion of the shoulder [ Time Frame: 10 years post-final reconstruction ]
   Differences between arms in range of motion of the shoulder measured at abduction/flexion with the patient sitting in front of a poster with a circle with degrees 0-180˚.Any difference ≥10 degrees defines defines restricted motion
9. Number of patients with capsular contracture [ Time Frame: 10 years post-final reconstruction ]
   Degree of capsular Contracture using Baker grading
10. Aesthetic outcome [ Time Frame: 10 years post-final reconstruction ]
    Aesthetic outcome scored bt the physician using breast Photo, on a scale from 0 to 3, 3 being worst

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Woman >18 years who are offered a mastectomy for invasive breast can-cer pT1-3, pN0-N3, M0 and wish reconstruction. The patient can be inclu-ded no matter the status of estrogen receptor, progesterone receptor, malignancy grade, and HER2 status.
• The patient is a candidate for loco-regional radiation therapy according to national or institutional guidelines.
• Highly selected patients with inflammatory breast cancer, namely those with complete or near complete response to neoadjuvant systemic thera-py judged by imaging and clinical examination before surgery. Any skin edema and clinical signs of skin involvement must have disappeared during systemic therapy. It is highly recommended that the decision to offer an inflammatory breast cancer patient inclusion in the DBCG RT Recon trial is made during a multidisciplinary team conference.
• Adjuvant systemic therapy with chemotherapy, endocrine therapy, anti-HER2 treatment and other targeted therapies used in the adjuvant setting either as new standard or as part of a trial during the course of the trial is accepted.
• Neoadjuvant chemotherapy and primary systemic therapy of an operable breast cancer is accepted.
• Patient with previous non-breast malignancy is accepted if the patient has been without disease minimum 5 years, and the treating oncologist esti-mates a low risk of recurrence. Patients with the following diseases can be accepted despite less than 5 years disease free interval: carcinoma in situ cervicis, carcinoma in situ coli, melanoma in situ, basal cell carcino-ma of the skin, squamous cell carcinoma of the skin.
• Life expectancy minimum 10 years.

Exclusion Criteria:

• Pregnant or lactating.
• Previous breast cancer or Ductal carcinoma in Situ (DCIS).
• Bilateral breast cancer.
• Previous radiation therapy to the chest region.
• Previous non-breast malignancy (not including carcinoma in situ of the cervix or colon, melanoma in situ, basal cell carcinoma of the skin, and squamous cell carcinoma of the skin) within 5 years.
• Conditions indicating that the patient cannot go through breast reconstruction, the radiation therapy or follow up.
• Not being able to participate due to language or other personal issues.
• Life expectancy less than 10 years.

Contacts and Locations

Contacts

Contact: Tove F Tvedskov, DMSc; +4535451028; tove.holst.filtenborg.tvedskov@regionh.dk

Contact: Peer M Christiansen, Professor; peerchri@rm.dk

Locations

Denmark

Ålborg Universitetshospital; Not yet recruiting

Aalborg, Denmark

Contact: Ute Hoyer

Sub-Investigator: Lene Brink-Sørensen

Sub-Investigator: Lars Lars Stenbygaard

Rigshospitalet/Herlev Hospital; Recruiting

Copenhagen, Denmark

Contact: Tove Tvedskov

Sub-Investigator: Rikke Bredgaard

Sub-Investigator: Lisbeth Hölmich

Sub-Investigator: Claus Kamby

Sub-Investigator: Tine Damsgaard

Esbjerg Sygehus; Recruiting

Esbjerg, Denmark

Contact: Lena Carstensen

Ringsted Sygehus; Not yet recruiting

Ringsted, Denmark

Contact: Lone Bak Hansen

Viborg Sygehus; Not yet recruiting

Viborg, Denmark

Contact: Inge Scheel Andersen

Åbenrå Sygehus; Not yet recruiting

Åbenrå, Denmark

Contact: Jügen Handler

Århus Universitets Hospital; Not yet recruiting

Århus, Denmark

Contact: Peer Christiansen

Sub-Investigator: Birgitte Vrou Offersen

Sponsors and Collaborators

Danish Breast Cancer Cooperative Group

Investigators

• Study Director: Birgitte V Offersen, Professor; DBCG
• Principal Investigator: Tove F Tvedskov, DMSc; DBCG
• Study Director: Tine Damsgaard, Professor; DBCG
• Study Director: Peer Christiansen, Professor; DBCG
• Study Director: Majbrit Jensen, MSc; DBCG

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kaidar-Person O, Nissen HD, Yates ES, Andersen K, Boersma LJ, Boye K, Canter R, Costa E, Daniel S, Hol S, Jensen I, Lorenzen EL, Mjaaland I, Nielsen MEK, Poortmans P, Vikstrom J, Webb J, Offersen BV. Postmastectomy Radiation Therapy Planning After Immediate Implant-based Reconstruction Using the European Society for Radiotherapy and Oncology-Advisory Committee in Radiation Oncology Practice Consensus Guidelines for Target Volume Delineation. Clin Oncol (R Coll Radiol). 2021 Jan;33(1):20-29. doi: 10.1016/j.clon.2020.09.004. Epub 2020 Sep 26.

• Responsible Party: Tove Filtenborg Tvedskov, Consultant, DMSc, Phd, associated professor, Danish Breast Cancer Cooperative Group
• ClinicalTrials.gov Identifier: NCT03730922
• Other Study ID Numbers: DBCG RT Recon
• First Posted: November 5, 2018
• Last Update Posted: February 15, 2023
• Last Verified: February 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Tove Filtenborg Tvedskov, Danish Breast Cancer Cooperative Group:

Breast cancer; Reconstruction; Post mastectomy radiotherapy

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases