High-dose-rate intraoperative radiation therapy (HDR-IORT) for retroperitoneal sarcomas

doi:10.1016/S0360-3016(99)00546-5

International Journal of Radiation OncologyBiologyPhysics

Volume 47, Issue 1, 1 April 2000, Pages 157-163

https://doi.org/10.1016/S0360-3016(99)00546-5 Get rights and content

Abstract

Purpose: Retroperitoneal sarcomas represent a formidable challenge to the treating oncologist due to their location, large size, and poor prognosis. The purpose of this study was to determine if the addition of high-dose-rate intraoperative radiation therapy (HDR-IORT) to surgery and external beam radiotherapy (EBRT) would improve the outcome in these patients.

Methods and Materials: Thirty-two patients with retroperitoneal soft tissue sarcoma were prospectively treated according to a protocol that included maximal tumor resection, HDR-IORT, and postoperative EBRT when feasible. Twelve patients presented with primary and 20 with locally recurrent disease. The tumors were high-grade in 20 patients and low-grade in 12 patients. Complete gross resection was achieved in 30 patients. HDR-IORT was given to a dose of 12–15 Gy. Additional EBRT was given to 78% of patients to a dose of 45–50.4 Gy. The two patients with gross residual disease received an additional I-125 permanent implant to a median peripheral dose of 140–160 Gy. The median follow-up was 33 months (range 1–77 mo).

Results: The 5-year actuarial local control rate for the whole group was 62%. For patients with primary disease, the local control rate was 74% compared to 54% in patients with recurrent disease (p = 0.4). The overall 5-year distant metastasis-free survival rate was 82%. In patients with high-grade tumors the rate was 70% vs. 100% in those with low-grade tumors. This difference was statistically significant, p = 0.05. The 5-year disease-free and overall survival rates were 55% and 45%, respectively. The most common type of post-treatment complication was gastrointestinal obstruction (18%) followed by fistula formation (9%), peripheral neuropathy (6%), hydronephrosis (3%), and wound complication (3%).

Conclusions: We are encouraged by the favorable local control rate and the acceptable morbidity with this new technique applied to a challenging patient population.

Introduction

Retroperitoneal sarcomas are rare tumors that account for 0.1% of all malignancies in the United States (1). Yet they represent a formidable challenge to the treating oncologist due to their proximity to vital structures and their propensity for local relapse. For the surgical oncologist, these tumors arise in an anatomical area with few fascial planes to contain them. Therefore it is not surprising that most retroperitoneal sarcomas present as locally advanced disease that can be massive. In addition they often encroach on major blood vessels or adjacent organs, making their resection problematic. Indeed, complete resection, defined as removal of all gross disease, can be obtained on average in 53% of patients (2), and in order to obtain such a resection inclusion of adjacent organs en bloc, resection is required in about 83% of cases (3). Furthermore, even in patients who have had complete gross resection, the rate of local relapse is quite high, with a 5-year local recurrence rate that ranges from 39% (4) to as high as 72% (2).

For the radiation oncologist the location and size, coupled with the proximity to nearby critical organs, limit the dose of radiation that can be delivered. This concern, plus the lack of a clear impact on overall survival, led some authors to question the use of adjuvant radiotherapy as a part of standard treatment in these patients (5). Extrapolation of data from two randomized trials of soft tissue sarcoma of the extremity and superficial trunk, however, suggests that delivery of high doses of radiation in combination with surgery favorably affects local control 6, 7. Therefore, the challenge is whether or not local control can be maximized with a possible survival benefit while minimizing normal tissue toxicity.

To overcome this dilemma, we developed a new treatment strategy that includes, in addition to surgery and external beam radiotherapy (EBRT), high-dose-rate intraoperative brachytherapy (HDR-IORT), which has been used successfully in rectal cancer (8). This type of approach could potentially improve the therapeutic ratio, since part of the radiation is delivered at the time of operation, with vital structures displaced out of the field or protected with special shielding. In addition, the type of applicator used in HDR-IOBRT, unlike electron-based IORT, is flexible in nature, allowing the treatment of tumor beds of almost any shape.

The purpose of this study was to evaluate the feasibility and potential morbidity of this new treatment modality and to determine its impact on local control, disease-free, and overall survival.

Section snippets

Methods and materials

Between 11/92 and 12/96, 49 patients with retroperitoneal soft tissue sarcomas were considered suitable for HDR-IOBRT. Forty out of 49 were enrolled in a Phase I/II prospective trial that included maximal tumor resection and HDR-IOBRT, followed by postoperative EBRT when appropriate. In addition, 9 other patients were treated according to the same guidelines, but off protocol.

Of the 40 patients enrolled in the Phase I/II trial, only 23 proceeded to have resection and HDR-IOBRT. The reasons for

Feasibility of procedure

The feasibility of the HDR-IORT procedure was assessed in terms of total operating room time, total IORT procedure time, actual IORT delivery time, estimated blood loss, and the total hospital stay (Table 2). The most important parameter Table 3 was the total IORT procedure time, which ranged from 30 to 240 minutes, with a median of 110 minutes. This wide range had to do with the size of the tumor bed, the complexity of the procedure, the dose delivered, and the activity of the high-dose-rate

Discussion

Retroperitoneal sarcomas represent about 15% of all soft tissue sarcomas. The main treatment modality for this disease continues to be surgery. The extent of surgical resection, however, is often limited in its scope due to the tendency of these tumors to invade into surrounding vital structures. The complete resectability rate has ranged from 38% (12) to 95% (13) with the results of other reports falling in between 14, 15. But even under these favorable conditions, the rate of local failure is

Acknowledgements

Leela Nathan, in preparation of this manuscript.

References (24)

C.P Karakousis et al.
Resectability of retroperitoneal sarcomasA matter of surgical technique?
Eur J Surg Oncol
(1995)
L.B Harrison et al.
High dose rate intraoperative radiation therapy (HDR-IORT) as part of the management strategy for locally advanced primary and recurrent rectal cancer
Int J Radiat Oncol Biol Phys
(1998)
J.E Tepper et al.
Complications of intraoperative radiation therapy
Int J Radiat Oncol Biol Phys
(1984)
C.N Catton et al.
Outcome and prognosis in retroperitoneal soft tissue sarcoma
Int J Radiat Oncol Biol Phys
(1994)
L.L Gunderson et al.
External beam and intraoperative electron irradiation for locally advanced soft-tissue sarcomas
Int J Radiat Oncol Biol Phys
(1993)
J.E Tepper et al.
Radiation therapy of retroperitoneal soft tissue sarcomas
Int J Radiat Oncol Biol Phys
(1984)
D.A Fein et al.
Management of retroperitoneal sarcomasDoes dose escalation impact on locoregional control?
Int J Radiat Oncol Biol Phys
(1995)
E.G Shaw et al.
Peripheral nerve and ureteral tolerance to intraoperative radiation therapyClinical and dose–response analysis
Radiother Oncol
(1990)
S.L Parker et al.
Cancer statistics, 1996
Cancer J Clin
(1996)
F.K Storm et al.
Diagnosis and management of retroperitoneal soft-tissue sarcoma
Ann Surg
(1991)

D.P Jaques et al.

Management of primary and recurrent soft-tissue sarcoma of the retroperitoneum

Ann Surg

(1990)

M.J Heslin et al.

Prognostic factors associated with long-term survival for retroperitoneal sarcomaImplications for management

J Clin Oncol

(1997)

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Progress in Retroperitoneal Sarcoma Management: Surgical and Radiotherapy Approaches
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IOeRT in retroperitoneal sarcoma: Towards more organ preservation with comparable oncological outcomes
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Retroperitoneal sarcomas (RPS) present a surgical challenge with high rates of local recurrence (LR). We investigated the role of intraoperative electron radiotherapy (IOeRT) in reducing LR after surgical resection of RPS.
A retrospective analysis of all patients who underwent surgical resection for RPS between 2014 and 2021 at a tertiary academic referral center (n = 172). Patients included underwent surgical resection of their RPS and received IOeRT (n = 36) and were compared by case control matching to patients with similar tumor characteristics (recurrence status and tumor grade) that did not receive IOeRT (n = 36).
The median length of hospitalization was 8 days (range, 4–34) in the IOeRT group and 10 days (range, 2–42) in the non-IOeRT group (p = 0.25). The mean operating room (OR) time was 4h (±1.3) and 4h (±1.9) in the IOeRT and non-IOeRT groups respectively, (p = 0.37). Complete resection with R0 margins was achieved in 30 patients (83.3%) and 24 patients (66.6%) in the IOeRT and non-IOeRT groups, respectively (p = 0.1). R1 resection was achieved in 6 patients (16.6%) and 12 patients (33.3%) respectively, (p = 0.1). The resected organ weighted score was significantly different between the groups; score 0 observed in 19 (52.7%) patients in the IOeRT group and 3 (8.3%) in the non-IOeRT group (p < 0.001), score 1 observed in 7 (19.4%) in the IOeRT group and 17 (47.2%) in the non-IOeRT group (p = 0.012). The rate of severe complications (CD score>3) did not differ between the groups, 5 (13.8%) patients in the IOeRT group and 9 (25%) patients in the non-IOeRT group (p = 0.23). No radiation associated complications were noted. The 2-year local recurrence free survival (LRFS) was 75.9% in the IOeRT group and 60.3% in the non-IOeRT group (p = 0.4). The 2-year IOeRT field recurrent free survival (IRFS) was 88.4% in the IOeRT group and 60.3% in the non-IOeRT group (p = 0.04).
The use of IOeRT did not increase the rate of surgical complications and was associated with superior local control in the radiation field, improved organ preservation without an impact on overall survival.
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This practice parameter was revised collaboratively by the American College of Radiology (ACR), the American Brachytherapy Society (ABS), and the American Society for Radiation Oncology (ASTRO).
Brachytherapy is a radiotherapeutic modality in which radionuclide or electronic sources are used to deliver a radiation dose at a distance of up to a few centimeters by surface, intracavitary, intraluminal, or interstitial application. Brachytherapy alone or combined with external beam radiotherapy plays an important role in the management and treatment of patients with cancer. High-dose-rate (HDR) brachytherapy uses radionuclides, such as iridium-192, at dose rates of ≥12 Gy/hr to a designated target point or volume, and it is an important treatment for a variety of malignant and benign conditions. Its use allows for application of high doses of radiation to defined target volumes with relative sparing of adjacent critical structures.
HDR brachytherapy requires detailed attention to personnel, equipment, patient and personnel safety, and continuing staff education. Coordination between the radiation oncologist and treatment planning staff and effective quality assurance procedures are important components of successful HDR brachytherapy programs.
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Citation Excerpt :
Local excision of solitary metastasis or debulking of intraabdominal recurrences has proved to provide effective palliation. Roles of adjuvant chemotherapy and radiotherapy have also been reported with varying outcomes.18,19 LMS of the IVC is a slow growing tumor with metastasis presenting late.
Leiomyosarcoma of the inferior vena cava (IVC-LMS) is a rare mesenchymal tumor arising from the tunica media. In this report, we describe the antesitum resection without inferior vena cava (IVC) reconstruction of retrohepatic IVC-LMS. To our knowledge, this is the first report of antesitum resection for IVC-LMS from India. A 51-year-old lady presented with features of Budd-Chiari syndrome and abdominal pain. Evaluation showed the tumor arising from IVC extending from above the renal veins and upto the subdiaphragmatic IVC. Blood investigations were normal with a positron emission tomography scan showing no metastatic disease. Antesitum, in situ resection of the IVC-LMS was performed. The patient recovered well postoperatively without renal or hepatic issues. Radical resection of IVC-LMS offers a chance for cure even in locally advanced status. Experience in complex liver resection and liver transplantation has made the resection of such tumors possible and safe.
Intraoperative radiation therapy (IORT) for soft tissue sarcoma – ESTRO IORT Task Force/ACROP recommendations
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To describe guidelines for the use of intraoperative radiation therapy (IORT) in the treatment of soft-tissue sarcomas (STS).
A panel of experts in the field performed a systematic literature review, supplemented their clinical experience and developed recommendations for the use of IORT in the treatment of STS.
Based on the evidence from the systematic literature review and the clinical experience of the panel members, recommendations regarding patient selection, incorporation into multimodal treatment concepts and the IORT procedure itself are made. The rationale for IORT in extremity and retroperitoneal STS is summarized and results of the major series in terms of patient and treatment characteristics, oncological outcome and toxicity are presented. We define surgical factors, volumes for irradiation, technical requirements, dose prescription, recording and reporting, treatment delivery and care during the course of IORT covering the main IORT techniques used for the treatment of STS.
In extremity STS, evidence originates from a few small prospective and mainly from retrospective single centre studies. Based on those reports, IORT containing-approaches result in very high local control rates with low rates of acute and late toxicity.
In retroperitoneal sarcomas, evidence is derived from one prospective randomized trial, a few prospective and a large number of retrospective studies. The randomized trial compared IORT combined with moderate doses of postoperative external-beam radiation therapy (EBRT) to high-dose postoperative EBRT alone after gross total resection, clearly favouring the IORT-containing approach. These results have been confirmed by the prospective and retrospective studies, which similarly showed high local control rates with acceptable toxicity, mainly favouring combinations of preoperative EBRT and IORT.
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^☆: Supported by NIH Grant RO1, CA 47179.

¹: Current address: Department of Radiation Oncology, Beth Israel Medical Center, New York, NY 10003.

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CLINICAL INVESTIGATIONHigh-dose-rate intraoperative radiation therapy (HDR-IORT) for retroperitoneal sarcomas☆

Abstract

Introduction

Section snippets

Methods and materials

Feasibility of procedure

Discussion

Acknowledgements

Eur J Surg Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Radiother Oncol

Cancer statistics, 1996

Cancer J Clin

Diagnosis and management of retroperitoneal soft-tissue sarcoma

Ann Surg

Management of primary and recurrent soft-tissue sarcoma of the retroperitoneum

Ann Surg

Prognostic factors associated with long-term survival for retroperitoneal sarcomaImplications for management

J Clin Oncol

CLINICAL INVESTIGATION
High-dose-rate intraoperative radiation therapy (HDR-IORT) for retroperitoneal sarcomas☆