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Dengsoe et al. Plast Aesthet Res 2024;11:25 https://dx.doi.org/10.20517/2347-9264.2024.20 Page 5 of 10

[15]
chemotherapy was 38 days in the free flap group and 28 days in the mastectomy-only group . Another
[16]
study detected a significant difference in the median time to initiation of chemotherapy in the free-flap
group (55 days) compared to the mastectomy-only group (40 days). Additionally, they analyzed the number
of patients whose initiation of chemotherapy exceeded a six-week, eight-week, ten-week, and 12-week time
point. Significantly more patients in the free flap reconstruction group had not started chemotherapy at
week 6, week 8, and week 10. At the 12-week point, there was no significant difference between the two
groups. The causes for delays in the free flap reconstruction group were mainly due to surgical
complications such as flap necrosis and abdominal wound dehiscence. In four cases, no reason was
recorded in the patient’s notes. In another study , the median time to initiation of chemotherapy was 27
[23]
days in the free flap group and 25 days in the mastectomy-only group. There were no cases of delay of more
than 12 weeks in either of the groups. The study by O’Connell et al. provides extensive data on the time to
initiation of adjuvant therapy . They detected a significant difference in the median time to initiation of
[24]
adjuvant therapy (either chemo- or radiotherapy) in the free-flap group (57 days) compared to the
mastectomy-only group (52 days). When looking particularly into delays of chemotherapy, there was no
significant difference between the proportion of patients who had started chemotherapy more than 12
weeks after surgery in the two groups. Correspondently, no significant difference was found in the
proportion of patients who had started radiotherapy after more than eight weeks. Notably, across all
patients, despite surgical procedures, the timing of adjuvant therapy, chemotherapy, and radiotherapy was
related to whether the patient had no, minor, or major complications. Likewise, patients experiencing
complications were significantly more likely to experience delays of chemotherapy for more than 12 weeks
and delays of radiotherapy for more than eight weeks. One study reported that patients with DIEP-flap
[26]
reconstructions received adjuvant chemotherapy on average, 35 days post-surgery and all within 7 weeks
after surgery. Two of the studies [22,25] defined that initiation of chemotherapy was delayed when it was
initiated after more than 8 weeks (56 days) and 6 weeks (42 days) after surgery, respectively. 21% of patients
in the free flap group had their chemotherapy initiated after more than 8 weeks compared to only 4.4%
among controls with mastectomy-only. Overall, 98% of patients who received adjuvant chemotherapy
[22]
started treatment within 12 weeks . Chemotherapy was delayed for more than six weeks in 47% of cases in
the free flap group compared to 22% of cases in the mastectomy-only group . The delay in initiation of
[24]
chemotherapy was mostly due to wound complications and it was concluded that postoperative
complications were a significant risk factor for delay.

DISCUSSION
Adjuvant chemotherapy
The majority of studies in this systematic review present data showing that immediate free flap
reconstruction might be associated with a longer time to initiation of adjuvant chemotherapy but that the
clinal significance of this delay is open to discussion.

Wilson et al. found a median difference of ten days (28 to 38) between the two groups . The study does not
[15]
perform a statistical test to compare the groups, but comments that the analyses suggest that free flap
reconstruction may lead to a delay in chemotherapy. They comment that the reason for delay was not
surgical complications, but rather a consequence of fatigue and the need for a longer recovery period among
patients in the free flap group. They clarify that data should be interpreted with caution due to the small
number of patients in the free flap group (ten patients). It should be noted that five out of ten patients
received their chemotherapy within 40 days and that the longest period between surgery and chemotherapy
was 52 days. These are both well within the period of 12-week delay, which, in large-scale population-based
studies, have shown to be associated with worsening of overall and cancer-specific survival [11,12] .