Clinical Phase I/II trial to Investigate Preoperative Dose-Escalated Intensity-Modulated Radiation Therapy (IMRT) and Intraoperative Radiation Therapy (IORT) in patients with retroperitoneal soft tissue sarcoma: interim analysis

Abstract

BackgroundTo report an unplanned interim analysis of a prospective, one-armed, single center phase I/II trial (NCT01566123).MethodsBetween 2007 and 2013, 27 patients (pts) with primary/recurrent retroperitoneal sarcomas (size > 5 cm, M0, at least marginally resectable) were enrolled. The protocol attempted neoadjuvant IMRT using an integrated boost with doses of 45–50 Gy to PTV and 50–56 Gy to GTV in 25 fractions, followed by surgery and IOERT (10–12 Gy). Primary endpoint was 5-year-LC, secondary endpoints included PFS, OS, resectability, and acute/late toxicity. The majority of patients showed high grade lesions (FNCLCC G1:18%, G2:52%, G3:30%), predominantly liposarcomas (70%). Median tumor size was 15 cm (6–31).ResultsMedian follow-up was 33 months (5–75). Neoadjuvant IMRT was performed as planned (median dose 50 Gy, 26–55) in all except 2 pts (93%). Gross total resection was feasible in all except one patient. Final margin status was R0 in 6 (22%) and R1 in 20 pts (74%). Contiguous-organ resection was needed in all grossly resected patients. IOERT was performed in 23 pts (85%) with a median dose of 12 Gy (10–20 Gy).We observed 7 local recurrences, transferring into estimated 3- and 5-year-LC rates of 72%. Two were located outside the EBRT area and two were observed after more than 5 years. Locally recurrent situation had a significantly negative impact on local control. Distant failure was found in 8 pts, resulting in 3- and 5-year-DC rates of 63%. Patients with leiomyosarcoma had a significantly increased risk of distant failure. Estimated 3- and 5-year-rates were 40% for PFS and 74% for OS. Severe acute toxicity (grade 3) was present in 4 pts (15%). Severe postoperative complications were found in 9 pts (33%), of whom 2 finally died after multiple re-interventions. Severe late toxicity (grade 3) was scored in 6% of surviving patients after 1 year and none after 2 years.ConclusionCombination of neoadjuvant IMRT, surgery and IOERT is feasible with acceptable toxicity and yields good results in terms of LC and OS in patients with high-risk retroperitoneal sarcomas. Long term follow-up seems mandatory given the observation of late recurrences. Accrual of patients will be continued with extended follow-up.Trial registrationNCT01566123.

Transanal total mesorectal excision for a large leiomyosarcoma at the lower rectum: a case report and literature review

“…Surgical margins were negative for tumor cells by this approach, but it was very close (<1 mm). There have been some reports on the effectiveness of radiotherapy against local recurrence [6, 13, 14], while radiotherapy was reported to be a risk factor for LMS [15]. Adjuvant radiotherapy or chemotherapy was not performed because there is no established adjuvant therapy for rectal LMS and the elderly patient did not hope to receive adjuvant therapies.…”

Tumoren des Retroperitoneums

“…Retroperitoneale Sarkome sind eine heterogene Gruppe von Tumoren mit unterschiedlicher Strahlensensibilität. Viele Studien setzen sich deshalb mit der Machbarkeit und den Ergebnissen von prä-, intra-und postoperativer Strahlentherapie bei RPS auseinander [2,20,26,30]. Aufgrund des Fehlens von randomisierten und prospektiven Studien kann keine allgemein gültige Aussage zur Stellung und Abfolge der Strahlentherapie getroffen werden, sie ist jedoch ein wichtiger Bestandteil und in der interdisziplinären Therapieplanung unbedingt zu diskutieren.…”

Intraoperative radiation therapy (IORT) in soft-tissue sarcoma

“…Compared to the postoperative approach, preoperative radiation therapy can offer several benefits, including a more precise target volume definition with smaller safety margins, reduced dose to adjacent organs at risk because of their displacement through the tumor itself, a possible devitalisation of tumor cells prior to surgery, fibrosis and thickening of the pseudocapsule, at least moderate tumor shrinkage and the avoidance of treatment delays due to postoperative complications [56, 58, 67]. This should result at least theoretically in less toxicity due to reduced doses in adjacent organs at risk but increased local control due to a more adequate target coverage which could be further enhanced by an intraoperative boost.…”

“…Several groups have evaluated combinations of preoperative and intraoperative radiation therapy and consistently reported high local control rates with acceptable toxicities (see Table 2) [57, 67–73]. For example Petersen et al [57] reported the Mayo experience with 87 patients, who have been treated with preoperative EBRT (mainly 45–50 Gy) followed by maximal resection and IOERT (median dose 15 Gy).…”

“…2) at the University of Heidelberg [56, 67]. Patients are eligible if they suffer from retroperitoneal sarcoma of any grade with a size ≥5 cm, are free of distant metastasis and deemed at least marginally resectable.…”