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Dengsoe et al. Plast Aesthet Res 2024;11:25 https://dx.doi.org/10.20517/2347-9264.2024.20 Page 3 of 10

The same inconsistency applies concerning the optimal timing of adjuvant radiotherapy. A meta-analysis of
21 retrospective studies has shown an increased risk of loco-regional recurrence if radiotherapy is delayed
[17]
for more than eight weeks after surgery . In contrast, another large cohort study found no significant
difference in survival with delays up to 20 weeks, though it should be noted that this accounts for patients
undergoing breast conserving surgery . The Danish Breast Cancer Group (DBCG) suggests that
[18]
radiotherapy should be initiated as soon as possible and that the maximum time from surgery should not
exceed 12 weeks .
[19]

In general, adjuvant therapy should be initiated as soon as possible, but it should await the complete healing
of the surgical wounds . Therefore, concerns have been raised that the increased complication rates
[10]
associated with immediate reconstruction may lead to a delay in the administration of adjuvant therapy
with the risk of compromising the oncological outcome . While psychosocial and cosmetic outcomes both
[20]
represent important considerations, it is important to keep in mind that a reconstructive procedure should
never compromise the overall oncological safety.

Several studies including systematic reviews have investigated the relationship between immediate breast
reconstruction and the initiation of adjuvant therapy [20,21] . Most studies are based primarily on implant-
based reconstructions or pedicled flap reconstructions and some studies do not even differentiate between
reconstructive methods. This systematic review seeks to evaluate and discuss whether post-mastectomy
immediate free flap reconstruction affects the timely initiation of adjuvant therapy.

METHODS
Search strategy and selection criteria
The Pubmed and Embase databases were searched to identify studies assessing the effect of immediate
breast reconstruction on the time to delivery of adjuvant therapy. A research librarian assisted in the search.
Databases were searched on November 22nd, 2023, and December 12th, 2023, respectively, with the terms
breast cancer and mastectomy and immediate autologous reconstruction and adjuvant therapy. Both MeSH
terms, free text words, and heading/abstract words were used. The search was limited to publications in
English. The exact search strategy is presented in Supplementary Table 1.

The inclusion criteria were observational studies reporting some kind of time frame from mastectomy
following primary free flap reconstruction to the start of adjuvant therapy, either chemotherapy or
radiation. Ideally, studies would also include a control group with women undergoing mastectomy only, but
this was not required. Studies that included only implant-based, pedicled-based and delayed reconstructions
were excluded. Additionally, studies with children, male patients, patients with metastasis or recurrence,
and pregnant or lactating women were excluded. Lastly, animal studies, case reports, editorial articles,
author reflection papers, and systematic reviews were excluded. Two investigators independently screened
titles and abstracts to identify studies meeting the defined eligibility criteria. Full-text articles were then
reviewed by the two plus one additional investigator and disagreements were resolved. The software tool
Covidence was used to manage and streamline the screening process.

Data extraction
Extracted data include author, publication year, country, study design, number of patients with free flap
reconstruction including type of free flap reconstruction, number of controls (mastectomy-only), and
number of patients receiving adjuvant treatment [Supplementary Table 2]. Additionally, complication rates
and time to initiation of adjuvant treatment in the two groups were extracted [Supplementary Tables 3 and
4].