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Dengsoe et al. Plast Aesthet Res 2024;11:25 https://dx.doi.org/10.20517/2347-9264.2024.20 Page 7 of 10

[26]
Nguyen et al.’s study is different from the others because the study designs lack a control group. Despite
this, it is still relevant to discuss their experiences with DIEP-flaps and correlate these to the other studies.
Adjuvant chemotherapy was initiated after a mean time of 35 days and all within 7 weeks after surgery.
[15]
[23]
These correlate well with the findings of Wilson and Lee but are notably shorter than the other
included studies [16,22,24] . The rate of complications was more than 50%, including four patients needing
further surgery due to either venous congestion or total flap loss. Those who underwent reoperation still
managed to initiate adjuvant therapy within 7 weeks, indicating that the complications did not lead to
clinically significant treatment delays. These findings are similar to those by Wilson et al. but stand in
contrast to the four other studies [15,16,22,24,25] which all describe that complications postpone the initiation of
adjuvant therapy to some extent, but not for longer than 12 weeks.

Adjuvant radiotherapy
Only one study by O’Connell et al. investigates how immediate free flap reconstruction affects the initiation
[24]
of adjuvant radiotherapy . It is well known that administering radiotherapy after implant-based
reconstruction is not recommended due to the significant risk of developing functionally and cosmetically
constraining capsular contractions [29,30] . In fact, there has been a tendency to refrain from immediate
reconstruction in general if the patient was expected to need adjuvant radiotherapy. For instance, the
Danish Breast Cancer Group (DBCG) has suggested opting for delayed breast reconstruction in these
situations . Two meta-analyses in 2017 and 2021 both conclude that immediate free flap
[32]
[27]
[31]
reconstruction should be considered a viable treatment option in patients requiring adjuvant radiotherapy.
Late complications were found to be comparable to those of delayed breast reconstruction. Additionally,
breast aesthetics and quality of life, evaluated from the patient's perspective, were not compromised by flap
exposure to radiation therapy. The optimal timing of adjuvant radiotherapy is not well-established. A meta-
analysis of 21 retrospective studies has shown an increased risk of loco-regional recurrence if radiotherapy
[17]
is delayed for more than eight weeks following surgery . In contrast, another large cohort study found no
significant difference in survival with delays of up to 20 weeks, though it should be noted that this accounts
for patients undergoing breast conserving surgery . The Danish Breast Cancer Group (DBCG)
[18]
recommends that radiotherapy should be initiated as soon as possible and that the maximum time from
surgery should not exceed 12 weeks . O’Connell et al. found that the prevalence of radiotherapy delays for
[19]
[24]
more than eight weeks was similar in the free-flap ground and the mastectomy-only group . There were
no examples of treatment delays of more than twelve weeks - regardless of procedure type or complications.
This study provides data showing that immediate free flap reconstruction in the setting of adjuvant
radiotherapy does not seem to affect loco-regional recurrence rates or survival. These findings support that
immediate free flap reconstruction could be considered a viable treatment option in patients requiring
adjuvant radiotherapy when the treatment is performed in experienced centers with integrated
collaboration between breast surgery, plastic surgery, and oncology.

In general, this systematic review presents data showing that immediate free flap reconstruction is
associated with a longer time to initiation of adjuvant therapy compared to mastectomy-only. The mean
[16]
[23]
difference between the two groups spanned from two days in Lee et al. to 14 days in Kontos et al. .
Adjuvant therapy was initiated after four to ten weeks in most cases - regardless of reconstruction or not -
and there were only few examples of delays of more than 12 weeks. Patients treated with mastectomy-only
were equally likely to experience delays of more than 12 weeks. Authors broadly comment that the clinal
significance of this difference between free flap reconstruction and mastectomy-only is expected to be
minimal or non-existing in most cases. As presented in the introduction of the review, the literature
generally agrees that delays in adjuvant therapy beyond 12 weeks after surgery are associated with increased
breast cancer recurrence and mortality, but uniform data on the clinical effects of delays within this interval
are lacking. A population-based study by Chaves-MacGregor et al. including 24,843 Californian women