International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationCarbon Ion Radiotherapy for Unresectable Retroperitoneal Sarcomas
Introduction
Surgery is the mainstay of treatment for retroperitoneal soft tissue sarcomas (RPSs). However, complete resection rates are in the range of 40% to 60%. Because of their anatomic location and propensity for spreading extensively, most tumors are advanced at the time of diagnosis, resulting in difficult resection and an inability to achieve negative margins. Many cases of positive margins or recurrence are detected after resection 1, 2, 3.
One-third of retroperitoneal tumors are soft tissue sarcomas known to be resistant to radiotherapy (RT), meaning that high-dose photon beams are necessary to achieve local control (LC) (4). In contrast to soft tissue sarcomas (STSs) of the extremity, LC rates greater than 90% are achieved with a combination of wide local excision and RT 5, 6, 7.
However, because of the limited radiation tolerance of the retroperitoneal, abdominal, and pelvic organs, adequate radiation doses are difficult to deliver, and toxicity can be significant. Various institutions have advocated preoperative or postoperative external beam RT, intensity-modulated radiation therapy (IMRT), intraoperative electron therapy (IORT), and brachytherapy (BT) for the adjunctive treatment of RPSs, with the goal of improving LC, reducing the likelihood of distant metastasis, and improving overall survival (OS). However, the role of systemic therapy also remains controversial 8, 9.
Between 1997 and 1999, a Phase I/II dose escalation study of CIRT trial for bone and soft tissue sarcomas (BSTSs) was conducted at the National Institute of Radiological Sciences (NIRS) 10, 11. It was concluded that CIRT is an effective local treatment for patients with BSTSs for whom surgical resection is not a viable option, and that CIRT seems to represent a promising alternative to surgery. There was no case of fatal toxicity, and no patient need a colostomy. The morbidity rate of CIRT has so far been quite acceptable. However, in our experience 8 of 64 patients (12.5%) had Grade 3 acute skin reaction and 6 of 60 (10%) had Grade 3 late skin reaction; the critical organs were skin/soft tissues for CIRT. The maximum tolerated dose (MTD) for those with subcutaneous tumor involvement was thought to be 70.4 GyE or less, and the MTD of 73.6 GyE was indicated for patients with no subcutaneous tumor. To confirm these findings, a Phase II clinical trial was conducted using two fixed carbon ion doses (70.4 or 73.6 GyE). There was no difference in LC between the outcomes of the two groups. Therefore, the recommended dose for BSTSs was decided at 70.4 GyE (10).
The purpose of this study was to evaluate the applicability of CIRT for unresectable retroperitoneal sarcomas with regard to normal tissue morbidity and local tumor control.
Section snippets
Methods and Materials
From May 1997 to February 2006, 24 patients (17 male and 7 female) with unresectable retroperitoneal sarcomas were treated with CIRT. The median follow-up time of all patients was 36 months (range, 6–143 months) and was retrospectively analyzed. Patients with primary tumors and recurrent tumors were included, but patients with distant metastasis were excluded. Sixteen patients had primary tumors and 8 had recurrent tumors. Twelve of the patients had undergone chemotherapy, all more than 4 weeks
Results
All patients were able to complete the planned CIRT without interruption. Median survival time of all patients was 41 months (range, 6–88 months). At 2 and 5 years, actuarial overall survival rates were 75% and 50% (Fig. 2). Six patients experienced local failure, with time from carbon ion therapy to local failure ranging from 3 to 36 months. One of the 6 patients who had local failure showed marginal recurrence close to the irradiated area. The remaining 18 patients had no evidence of local
Discussion
Our institution started a Phase I/II clinical study using CIRT and demonstrated the clinical efficacy of this RT on various kinds of malignant tumors 10, 11. The study produced good LC of BSTSs, including RPSs, generally considered to be photon resistant and inoperable. Despite the fact that patients with RPSs in our series had been considered mostly to involve tumors that were unresectable, radioresistant, and located deep in the trunk, we experienced good LC, OS and a relatively low incidence
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Conflict of interest: none.