Most of the evidence for neoadjuvant radiotherapy in sarcoma are derived from multiple randomized trials in extremity sarcoma [20]. However, at the same time, it is well recognized that those patients are at increased risk of post-operative complications including poor wound healing and surgical site infections, as shown in a randomized trial, where the rate of wound complication was twice as common in the neoadjuvant group (35%) when compared to the adjuvant radiation cohort (17%) [21]. Using the database at Samsung Medical Center, we have found that the patients in the neoadjuvant group for retroperitoneal sarcoma were older and the primary tumor was significantly larger, consisting largely of G2 liposarcoma. In contrast to concerns about adverse effects of radiotherapy, the use of pre-operative radiotherapy did not demonstrate any significant impact on the operative time, the length of hospital stay, the need for intra-operative transfusion and re-operation, and severe post-operative complications defined as CD ≥ 3. The rate of concomitant adjacent organ resection was similar between the groups. However, a statistically significant increase was observed in the need for post-operative transfusion and unplanned admission to ICU in the preRTx patients. The age and tumor size did not show any significant association, but pre-operative RT was an independent risk factor for the post-operative transfusion (p = 0.009). Therefore, we recommend that a meticulous bleeding control is accomplished during operation in those patients. Overall, these findings suggest that the use of pre-operative radiotherapy is safe, and this is in keeping with previous analysis from NSQIP data. Nussbaum et al. investigated a total of 785 patients undergoing RPS resection, where 71 patients (9%) received pre-operative radiotherapy and reported that the pre-operative RT did not increase 30-day morbidity or mortality [7]. Bartlett et al. also used the NSQIP data, analyzing 696 patients where 70 patients (10%) received pre-operative radiotherapy, and reported similar findings [16].
In terms of the radiation therapy, previous studies have reported that RT dose escalation resulted in improved local control, tumor response, and even cancer-specific survival in various solid tumors [22–26]. With the advancement of RT techniques, considerable efforts have been directed towards delivery of higher dose radiation, especially in the radiation-resistant solid tumors [27]. However, evidence regarding the benefit of dose escalation in neoadjuvant RT for retroperitoneal sarcoma is very limited. In our knowledge, only one study by Tzeng et al. investigated the feasibility and outcomes of dose escalation in the pre-operative RT with selective dose escalation to the margin at risk for the patients with retroperitoneal sarcoma [28]. In that study, 45 Gy in 25 fractions was delivered to the entire tumor bed and surrounding margin and the boost dose up to 57.5 Gy to the volume predicted as high risk for positive surgical margins. Despite the reports of tolerability of such radiotherapy regimen and high rates of tumor response and complete resection, subsequent analysis of the relevant clinical outcomes from dose escalation in neoadjuvant setting has not been conducted. Instead, intraoperative RT boost with dose escalation has been attempted for the at-risk area in addition to the neoadjuvant RT, the results of which demonstrated improved local control and overall survival [5, 29, 30]. In our cohort, we have found that higher dose of radiation was possible in the pre-operative radiotherapy group with median dose of 62.5 Gy, which was even higher than that in the TE group (median dose of 58.8 Gy), and it was overall well tolerated. This is helpful as the pre-operative RT is often preferred over adjuvant RT for the protective effect from the primary retroperitoneal sarcoma on the adjacent radiosensitive organs [31].
The overall survival and local recurrence free survival did not demonstrate statistically significant difference between the three groups. However, it requires a careful interpretation as the analysis is limited by the short-term follow up period in the preRTx group, where the other two groups had 2–3 times longer follow up duration, and this difference was statistically significant (p < 0.001). The authors are planning to conduct subsequent analysis with longer follow up to better assess the oncological and survival benefit of the pre-operative radiotherapy. This study has other limitations to note. Most importantly, the retrospective nature of the study conducted at a single institution entails potential selection bias, and our findings may not be generalizable to other cohorts of patients. In addition, a small sample size, particularly in the pre-operative group, further limits the study, although the issue of overall small sample size is somewhat attributed to the low incidence of retroperitoneal sarcoma. Nonetheless, our study demonstrates that the addition of pre-operative RT to curative resection of retroperitoneal sarcoma does not appear to increase the peri-operative morbidity and mortality, and that it is safe and feasible.