Postoperative Adjuvant Irradiation: Effects on Tranverse Rectus Abdominis Muscle Flap Breast Reconstruction

Nho V. Tran, M.D., Gregory R. D. Evans, M.D., Stephen S. Kroll, M.D., Bonnie J. Baldwin, M.D., Michael J. Miller, M.D., Gregory P. Reece, M.D., and Geoffrey L. Robb, M.D.
Houston, Texas

Immediate breast reconstruction has become the standard of care for women seeking restoration after mastectomy. It offers the advantages of a better aesthetic outcome by preservation of the breast skin envelope; avoidance of delayed surgery, which usually results in additional scarring; and enhanced psychological benefits. Recently, immediate reconstruction has become more accepted in the treatment of more advanced disease. Such patients usually require postoperative adjuvant chemotherapy and radiation. Because adjuvant irradiation indications are extended to include early breast cancers, we will undoubtedly see more patients who will undergo postoperative irradiation to the breast transverse rectus abdominis muscle (TRAM) flap.1,2 The negative outcome of implant-based reconstruction in light of prior postoperative irradiation is well documented in the literature.3-8 In contrast, the effects of irradiation on autologous TRAM breast reconstruction are still poorly defined. This study evaluated the effects of postoperative irradiation on immediate free and pedicled TRAM flap breast reconstruction.

FIG. 1. (Above) Thirty-three-year-old patient with a left TNM infiltrating ductal carcinoma who underwent left modified radical mastectomy and right simple prophylactic mastectomy. Bilateral immediate reconstruction was performed with a free TRAM flap. Postoperative 5-flourouracil, doxorubicin, cyclophosphamide chemotherapy was initiated for 4 cycles. (Below) Six months after surgery, adjuvant fractional radiotherapy of 55 Gy was administered to the left side to reduce the risk of local recurrance. The patient is shown 1 year after irradiation with a reasonable outcome.

Methods

A retrospective review was conducted of 1443 patients who had undergone TRAM (1006 free and 437 pedicled) breast reconstructions at the University of Texas M. D. Anderson Cancer Center between 1988 and 1998. Sixty-four patients had received postoperative irradiation to the TRAM flaps and axilla between 6 months and 1 year after surgery. This delay period was necessary for completion of adjuvant chemotherapy, which began 3 weeks after surgery in all except two patients. Adjuvant chemotherapy regimens included S-fluorouracil, doxorubicin, cyclophosphamide in most patients; and paclitaxel, cyclophosphamide, methotrexate, S-fluorouracil, and bone marrow transplantation in three patients. To evaluate the long-term effects of radiation therapy on TRAM flap breast reconstruction, we included only those patients with at least 1 year of follow-up from radiation treatment. Forty-one patients (36 white, 3 black, and 2 Hispanic) with a median age of 48 years fulfilled these criteria. All were nonsmokers at the time of reconstruction. An average fractionated irradiation dose of 50.99 Gy was administered over 5 weeks to the operative bed or flap of patients with close margins, positive margins, extralymphatic invasions, stage II breast cancer with >4 positive nodes, and stage III and IV disease. All patients except three received irradiation at M. D. Anderson Cancer Center. The 14 bilateral reconstruction patients with unilateral irradiation allowed us to compare the observed difference between the two sides in a given patient. Flaps were evaluated (without clothing) for volume loss, hyperpigmentation, palpable fat necrosis, firmness, skin contracture, flap contracture equivalent to Baker grades III and IV, and loss of symmetry. Data were collected retrospectively from personal communication, physical examinations, charts, and photographic reviews. The minimum follow-up period was 1 year, with an average follow-up of 3 years after completion of radiation therapy. Chi-square and Fisher's exact tests were used to analyze the data.

FIG. 2. Fifty-four-year-old patient with stage II breast cancer who received postoperative adjuvant fractionated radiation therapy with 50 Gy to the TRAM flap 6 yeats after completion of treatment. The left breast was reduced at the time of TRAM flap reconstruction and initially matched the opposite side.

Results

One year after completion of adjuvant radiotherapy, the most striking finding was that 10 of 41 flaps (24 percent) demonstrated severe contracture and required a secondary flap to obtain acceptable results. Three were described as "contracted implants" by the medical oncologists. Fat necrosis occurred in 14 of 41 flaps (34 percent). These palpable, firm areas were documented as fat necrosis by trucut needle biopsies during subsequent tumor surveillance. Five flaps developed new fat necrosis following irradiation, which was higher than the 7 percent fat necrosis rate in our nonirradiated TRAM population. Two patients with free TRAMs and a history of smoking had persistent fat necrosis at 3 and 5 years, respectively. Fifty-six percent of the irradiated flaps were firm. Only 17 percent of patients (7 of 41) achieved and maintained symmetrical reconstructions. Table I details the results of the irradiated pedicle versus free TRAM flaps. Eleven of 41 patients pursued a total of 20 surgical revisions and/or manipulations of the opposite or irradiated breast to obtain symmetry. However, despite these interventions, symmetry was not maintained in these patients. Postoperatively, the irradiated flaps fared worse statistically (p < 0.0001) for skin hyperpigmentation, fat necrosis, firmness, and flap contracture than the nonirradiated flaps of the 1443 TRAIVI control subjects at our institution. Table II summarizes the bilateral reconstruction results of the patients who had radiotherapy only on one side. Twenty-four patients with irradiated flaps had nipple areolar reconstruction, and only one patient maintained acceptable projection.

FIG. 3. (Above) Thirty-five-year-old patient who underwent bilateral skin sparing mastectomies with immediate free TRAM reconstruction for a left TNM infiltrating ductal carcinoma and prophylaxis on the right side. (Below, left) Postoperative chemotherapy of 5-flourouracil, doxorubicin, cyclophosphamide and bone marrow transplant were performed. Adjuvant fractionated irradiation of 60 Gy was initiated 7 months after surgery to reduce risk of local recurrance. (Below, right) Note the patient's irradiated left firm breast mound at 16 months after irradiation. The breast mound continues to demonstrate upward migration and contraction after three attempts at revision. The right side remains soft.

Discussion

Unlike the negative outcome of implant-based breast reconstruction, the fate of TRAM flap reconstruction following adjuvant irradiation has been poorly elucidated. We observed these changes at least 1 year after radiotherapy in an attempt to eliminate the early effects of acute irradiation on the reconstruction. Early findings tend to demonstrate good outcome.9 However, the later fibrosis damage is more important to the ultimate outcome of the breast mound. Recent radiation literature by Moulds and Berg,2 Zimmerman et al.,10 and others detailed modern radiation techniques and "often excellent cosmetic outcome," according to their patients. Aesthetic issues are quite subjective, and we are certainly more critical than the patients when judging results. Thus, to avoid controversy, we did not grade the cosmetic outcome.
Little can be learned from comparing the free to pedicled TRAM groups in this study, because the small sample sizes preclude any statistically significant conclusion. As a whole, however, our results are significant with regard to symmetry, fat necrosis, and contracture when comparing the irradiated group with the 1443 nonirradiated TRAM controls. There was no flap loss secondary to the adjuvant therapy. However, the most striking finding is the 10 contracted, distorted breast mounds (24 percent). These 10 irradiated flaps required another flap to correct the deficient skin and soft tissue volume. Interestingly, of the 10 flaps, 9 were from the free TRAM group. The patients with distorted flaps use external prostheses to achieve symmetry in clothing. The breast conservation literature reports a 15 to 25 percent adverse result that requires correction with further flap surgery.11, 12 Despite the robust blood supply of the free TRAM flap, it, too, seems not to tolerate adjuvant irradiation unscathed.
Fat necrosis was considerably higher compared with other postoperative nonirradiated TRAM patients (34 percent versus 7 percent; p < 0.0001). For patients with existing fat necrosis after surgery and chemotherapy, the damage persisted. Five patients developed new fat necrosis after radiotherapy.

Only seven patients (17 percent) achieved and maintained symmetry. Skin and subcutaneous contracture displaced the breast mounds superiorly and away from the inframammary folds. This progressive contraction produces asymmetry and even deformity. Finally, just nine flaps (22 percent) remained soft and symmetrical (Fig. 1). The 14 bilateral reconstruction patients with unilateral irradiation further support the negative influences of radiation on TRAM flaps inasmuch as only one patient achieved and maintained symmetry. In these same patients, the nonradiated sides have remained soft and ptotic. These findings are similar to those of Williams et al. after their experience with 19 irradiated pedicled TRAM flaps (Fig. 2).13
Surgical revisions produced unpredictable outcomes in the irradiated breast mound. Only 11 of 41 patients pursued a total of 20 revisions and/or manipulations of the opposite or irradiated breast to obtain symmetry. In the end, the asymmetry persisted (Fig. 3).

Finally, nipple areolar reconstruction in the irradiated flap is often met with complete loss of projection. Of the 24 patients with nipple areolar reconstruction, only one maintained adequate projection.
The sample size is too small to allow any significant comparison between the pedicled and the free flap groups. One can speculate, however, that the pedicled TRAM group may demonstrate more severe fat necrosis and contracture owing to the poorer vascular supply. As a whole, postoperatively irradiated flaps fared worse statistically (p < 0.0001) for skin hyperpigmentation, fat necrosis, firmness, and flap contracture when compared with the 1443 nonirradiated control TRAM flaps at our institution.

The above unpredictable, adverse changes make it difficult to obtain consistent results for patients with immediate breast reconstruction and postoperative adjuvant irradiation. No other predisposing medical conditions were identified to make the patient more susceptible to irradiation changes. The definitive origin of these changes is unknown, but they most likely result from the perivascular inflammation and fibrosis seen after radiotherapy. Immediate TRAM reconstruction in this setting should be approached cautiously. It may be appropriate to consider delayed surgery for some patients. Patients should be aware that multiple revisions and additional flaps might be necessary to correct the progressive deformity from radiation therapy. Perhaps making the initial flap larger will account for postirradiation shrinkage.

In summary, despite no flap loss, immediate breast reconstruction with TRAM flap in postoperative adjuvant radiation should be approached with caution inasmuch as the long-term outcome may be unpredictable. More investigation is required before final recommendations can be developed for this patient population.

Gregory R. D. Evans, M.D.
University of California, Irvine
101 The City Drive
Bldg. 55, Rte. 81
Orange, Calif 92868
gevans@uci.edu

From the Department of Plastic Surgery at the University of Texas M. D. Anderson Cancer Center. Received for publication September 7, 1999; revised November 29, 1999.
Presented at the American Society for Reconstructive Microsurgery Meeting in Kona, Hawaii, on January 17, 1999.