Japanese Journal of Clinical Oncology 31:237-239 (2001)
© 2001 Foundation for Promotion of Cancer Research
Editorial |
Perioperative High Dose Rate Brachytherapy for Soft Tissue Sarcoma
Division of Multidisciplinary Radiotherapy, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
Cancer Cure and Conservative Treatment
Cancer is one of the major causes of death worldwide. In Japan, cancer has been the leading cause of death since 1981. Recent analysis based on the Osaka Cancer Registry shows a significant improvement of 5-year relative survival rates at all sites from 30.4% in 1975–77 to 41.0% in 1990 (1). Although aggressive treatment such as super-radical surgery plays an important role in the improved outlook with respect to cancer survival, such an improvement may do so with loss of an organ and its function. In certain circumstances physicians as well as patients may wish for more limited surgery with organ preservation to afford better quality of life, which is important for cancer patients and their family. One such example is limb-sparing surgery for soft tissue sarcomas of the extremities. Following such surgery, radiotherapy is an essential adjunct if cure/local control, comparable to that of more radical surgery, is to be afforded.
Radiotherapy was long considered ineffective against bone and soft tissue sarcomas, these malignancies often being labeled ‘radioresistant’. Clinical experience has demonstrated, however, that some sarcomas will respond dramatically to fractionated radiotherapy. There is the extensive experience of limb salvage surgery with pre- and postoperative radiotherapy. Local control rates in excess of 75% following limb salvage surgery and postoperative radiotherapy have resulted in widespread acceptance of limb preservation with a corresponding reduction in amputation rates.
Pre- or Postoperative Radiotherapy
Enneking et al. (2) proposed the division of surgical resection margins into three types: (i) wide, (ii) marginal and (iii) intralesional. Local recurrence rates vary from 30 to 60% for wide margins and are >70% and >90% for marginal and intralesional margins, respectively (3). At the present time in Japan, postoperative external beam radiotherapy (EBRT) is the gold standard for bone and soft tissue sarcomas. Although preoperative radiotherapy resulted in extremely high local control rates for soft tissue sarcomas of extremities, there remains some doubt as to whether preoperative radiotherapy requires a ‘boost’ of intra- or postoperative radiotherapy. Orthopedic surgeons usually preferred to administer preoperative chemotherapy instead of radiotherapy. Intraoperative electron beam radiotherapy (IOERT) has been assessed for soft tissue sarcomas in a few hospitals.
IORT Using Electron Beam or Brachytherapy
Intraoperative radiotherapy (IORT) is a treatment modality in which resectable lesions are removed surgically and the remaining cancer nests are sterilized by irradiation during the surgical procedure. IORT is usually performed with an electron beam (IOERT), since specific beam energy can be chosen to produce the desired depth of tissue penetration with a sharp fall-off of radiation dose, thereby avoiding the problems caused by exposure of normal tissue beneath the tumors.
As of November 1998, 65 high dose rate (HDR) Ir-192 remote afterloaders and 149 HDR Co-60 remote afterloaders were operated in Japan. The HDR Ir-192 remote afterloader enabled us to perform perioperative brachytherapy (4), which has some advantages over IOERT. IOERT needs much equipment and staff. In addition, a single large dose of IOERT may cause late adverse effects to the surrounding healthy organ. Moreover, overlying skin is not included for the tumor-bed target in IOERT. Consequently, the tumor bed consists of the tissue over, under and around the tumor, bearing its ramifications. After excision of the tumor, the overlying skin and soft tissues collapse onto the underlying structures. The resulting composite slab of tissue constitutes the tumor-bed target for radiation therapy (5). Perioperative brachytherapy is able to shorten the treatment duration and resulted in a reduced duration of hospital stay compared with pre- or postoperative EBRT.
Recently, IORT has mainly been divided into two techniques: (i) IOERT and (ii) intraoperative setting of low dose rate (LDR) or high dose rate (HDR) implants/catheters to deliver LDR or HDR perioperative brachytherapy. A randomized study from Memorial Sloan Kettering Cancer Center concluded that debulking surgery with tumor bed brachytherapy resulted in a significantly higher control rate than without brachytherapy (5). Concerning LDR- and HDR-IORT, the standard dose for tumor bed implants was 40–48 Gy. EBRT of 30–50 Gy should be given if all macroscopic tumor had not been resected. The implant boost dose was 15–24 Gy. Despite treating high-grade malignancy, local control rates were good (
75%).
Shiu et al. (5) reported that four of 47 patients developed radiation-induced peripheral nerve injury after Ir-192 LDR tumor bed brachytherapy after resection of soft tissue sarcoma of the limb. The total dose to the neurovascular bundle was exceptionally high for these four patients, 91–148 Gy. In contrast, none of the 43 patients treated with <90 Gy developed peripheral nerve injury. They stressed that postponing the loading of radiation sources until after the fifth postoperative day reduced the rate of serious wound complications.
HDR-IORT Experience at the Osaka University Hospital
We use the term of perioperative hyperfractionated brachytherapy, which consists of intraoperative tubing and postoperative hyperfractionated radiotherapy (4). Postoperative HDR hyperfractionated brachytherapy was started on days 4–13 (median, day 6) after surgery using Microselectron-HDR. The total dose was 40–50 Gy in 7–10 fractions over 4–7 days using fractionation twice a day with a minimum gap of 6 h at 5 mm from the plane of sources.
From 1992 through 1996, 16 lesions in 14 patients with bone and soft tissue sarcomas were treated with perioperative hyperfractionated brachytherapy. The median age was 39 years (range, 14–72 years). There were nine males and five females. Median follow-up was 30 months (range, 19–46 months). The resection margins were classified as intralesional in five lesions, marginal in five and wide in six. Ultimate local control was achieved in eight of 16 lesions (50%). None of the five lesions with intralesional resection margins was controlled. In contrast, four of five and four of six lesions with marginal and wide resection margins, respectively, were controlled. Three patients died of both tumor and metastasis, three of metastasis alone and one of tumor alone and seven showed no evidence of disease. Peripheral nerve palsy was seen in one case 6 months after perioperative HDR brachytherapy. His ulnar nerve received a dose of >50 Gy in 10 fractions over 6 days with a single catheter. No infection or delayed wound healing has been observed so far.
We conclude that perioperative HDR hyperfractionated brachytherapy of 40–50 Gy in 7–10 fractions over 4–7 days is safe, well tolerated and applicable to marginal or wide surgical margin cases.
The ABS Recommendations for Brachytherapy of Soft Tissue Sarcomas
The members of the American Brachytherapy Society (ABS) with expertise in soft tissue sarcoma formulated brachytherapy guidelines based upon their clinical experience and a review of the literature (6).
Brachytherapy used alone or in combination with EBRT is an established means of safely providing adjuvant local treatment after resection for soft tissue sarcomas. Brachytherapy options include LDR techniques with Ir-192 or I-125, fractionated HDR brachytherapy or intraoperative HDR therapy. Recommendations are made for patient selection, techniques, dose rates and dosages. Complications and possible interventions to minimize their occurrence and severity are reviewed.
Brachytherapy represents an effective means of enhancing the therapeutic ratio, offering both biological and dosimetric advantage. The treatment approach used depends upon the institution, physician expertise and the clinical situation. Guidelines are established for the use of brachytherapy in the treatment of soft tissue sarcomas. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose-reporting policies. These guidelines will be modified as further clinical results become available.
Comments on Chun et al.’s Paper
Chun et al. (7) in this issue present a retrospective review of clinical experiences with combined modality of HDR brachytherapy and EBRT for primary and recurrent soft tissue sarcoma. They report their experience of postoperative brachytherapy and EBRT for soft tissue sarcoma with neither local failure within the radiation field nor significant radiation-related complications at the time of writing the paper. The immediate hyperfractionated postoperative HDR brachytherapy with total dose of 12–18 Gy over 3 days (b.i.d.) and combined modality with EBRT resulted in the above excellent results. Since they reduced the dose of EBRT by using the HDR brachytherapy as a boost, there was very little of the chronic complication of subcutaneous fibrosis. Moreover, they did not encounter the neuropathy owing to the careful placement of catheters and coverage of neurovascular bundle with muscle or gel-foam so as not to contact these structures with the catheters.
At their clinic, the surgeon placed the catheters parallel to the long axis of the tumor bed. In contrast, at the Osaka University Hospital, after surgical removal of the gross tumor, a radiation oncologist marked the tumor bed with metal clips and inserted a series of parallel catheters percutaneously into the target. There is a difference of opinion by surgeons and radiation oncologists between Ajou University and Osaka University.
This procedure is attractive and promising for the more conservative treatment of soft tissue sarcomas. It was significantly indicated that hyperfractionated brachytherapy safely replaced the LDR brachytherapy in the postoperative procedure.
REFERENCES
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2 Enneking WF, Spanier SS, Malawer MM. The effect of the anatomic setting on the results of surgical procedures for soft parts sarcoma of the thigh. Cancer 1981;47:1005–22.[Medline]
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4 Koizumi M, Inoue TA, Yamazaki H, Teshima T, Tanaka E, Yoshida K, et al. Perioperative fractionated high-dose rate brachytherapy for malignant bone and soft tissue tumors. Int J Radiat Oncol Biol Phys 1999;43:989–93.[Medline]
5 Shiu MH, Hilaris BS, Harrison LB, Brennan MF. Brachytherapy and function-saving resection of soft tissue sarcoma arising in the limb. Int J Radiat Oncol Biol Phys 1991;21:1485–92.[Medline]
6 Nag S, Shasha D, Janjan N, Petersen I, Zaider M. The American Brachytherapy Society recommendations for soft tissue sarcomas. Int J Radiat Oncol Biol Phys 2001;49:1033–43.[Medline]
7 Chun M, Kang S, Kim B-S, Oh Y-T. High dose rate interstitial brachytherapy in soft tissue sarcoma: technical aspect and results. Jpn J Clin Oncol 2001;31:279–83.
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