Japanese orthopaedic association (JOA) clinical practice guidelines on the management of malignant bone tumors - Secondary publication.

BACKGROUND: In Japan, there are currently no general guidelines for the treatment of primary malignant bone tumors. Therefore, the Japanese Orthopaedic Association established a committee to develop guidelines for the appropriate diagnosis and treatment of primary malignant bone tumors for medical professionals in clinical practice. METHODS: The guidelines were developed in accordance with "Minds Clinical Practice Guideline Development Handbook 2014″ and "Minds Clinical Practice Guideline Development Manual 2017". The Japanese Orthopaedic Association's Bone and Soft Tissue Tumor Committee established guideline development and systematic review committees, drawing members from orthopedic specialists leading the diagnosis and treatment of bone and soft tissue tumors. Pediatricians, radiologists, and diagnostic pathologists were added to both committees because of the importance of multidisciplinary treatment. Based on the diagnosis and treatment algorithm for primary malignant bone tumors, important decision-making points were selected, and clinical questions (CQ) were determined. The strength of recommendation was rated on two levels and the strength of evidence was rated on four levels. The recommendations published were selected based on agreement by 70% or more of the voters. RESULTS: The guideline development committee examined the important clinical issues in the clinical algorithm and selected 22 CQs. The systematic review committee reviewed the evidence concerning each CQ and a clinical value judgment was added by experts. Eventually, 25 questions were published and the text of each recommendation was determined. CONCLUSION: Since primary malignant bone tumors are rare, there is a dearth of strong evidence based on randomized controlled trials, and recommendations cannot be applied to all the patients. In clinical practice, appropriate treatment of patients with primary malignant bone tumors should be based on the histopathological diagnosis and degree of progression of each case, using these guidelines as a reference.

Novel sluggish speed signs on ultrasound is indicative of hemangiomas.

Background Hemangiomas are sometimes difficult to diagnose with current techniques. Sluggish speed signs (SSS) are a phenomenon that: (i) cannot be depicted as Doppler flow on Doppler ultrasound; (ii) can be observed as fluid movements on Doppler ultrasound; and (iii) cannot be depicted as waveforms on pulse Doppler mode. We hypothesized that SSS could be diagnostic indicators for hemangiomas. Purpose To evaluate whether ultrasound findings, in particular those relating to SSS, are a reliable tool for detecting hemangiomas compared to magnetic resonance imaging (MRI) and the gold standard for hemangioma diagnosis: pathological examination by biopsy or after surgical resection. Material and Methods Totally, 105 patients (mean age, 44.9 years) with soft-tissue tumors underwent MRI and ultrasound examination before biopsy or tumor resection. Ultrasound findings were compared with MRI as well as pathological findings, which were used as reference. Results Hemangiomas were identified in 16 (6.25%) of the 105 patients. On MRI, flow voids showed sensitivity and specificity values of 81.3% and 96.6%, respectively. On ultrasound examination, SSS was the only finding to show equally high sensitivity (93.8%) and specificity (96.6%) for diagnosing hemangiomas. There was no significant difference in the diagnostic capabilities between these two parameters ( P = 0.479). Conclusion SSS showed a high sensitivity and specificity for diagnosing hemangiomas and therefore are useful diagnostic tools to supplement MRI.

Factors associated with the decision of operative procedure for proximal femoral bone metastasis: Questionnaire survey to institutions participating the Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group.

BACKGROUND: Pathological fracture of the proximal femur is a main cause of cancer patients losing their ability to walk. Although both osteosynthetic devices (predominantly intramedullary nails) and prosthetic replacement have been widely performed for treatment, controversies exist regarding which procedure should be used for the various conditions. In order to decide the eligibility criteria of a planned randomized prospective study about the treatment of pathological fractures of the proximal femur, we assessed the factors affecting the selection of operative procedures using questionnaires sent to the members of the Bone and Soft Tissue Tumor Study Group (BSTTSG) of the Japan Clinical Oncology Group (JCOG). METHODS: Questionnaire surveys to evaluate (1) the priority levels of the factors, (2) the equipoise range of each factor in situations where either procedure could be applied, (3) risk and benefit of each procedure, and (4) the degree of bone destruction affecting the selection of operative procedures, were sent to 26 institutions. RESULTS: Over 80% of the institutions answered. Orthopaedic surgeons of BSTTSG decided on the procedure according to the following factors in descending order: life expectancy, performance status before fracture, the degree of bone destruction, walking ability before fracture, general complications, the number of bone metastases in other sites, and the visceral metastasis status. With regard to bone destruction, (1) the involvement of the head, neck, calcar, and intertrochanteric region, (2) transverse destruction >1/2, and (3) soft-tissue tumor extension, were the factors that led to the choice of prosthesis treatment. CONCLUSIONS: Using these identified factors, the inclusion criteria for the prospective randomized study of the surgical treatment of metastatic bone tumors of the proximal femur were optimized. The evaluation system about the bone destruction of metastases needs to be refined through the following prospective randomized study.

Does expression of glucose transporter protein-1 relate to prognosis and angiogenesis in osteosarcoma?

BACKGROUND: The survival of patients who present with nonmetastatic extremity osteosarcoma has dramatically improved, but there are some patients who do not respond to chemotherapy. The ability to identify patients with a poorer prognosis might allow us to target different therapy for these patients. Glucose transporter protein-1 (Glut-1), one of the key factors in glucose metabolism, has been reported to be an independent prognostic factor in various tumors. However, little is known about the role of the Glut-1 pathway in osteosarcoma. QUESTIONS/PURPOSES: We asked (1) if Glut-1 expression is a prognostic marker for survival in patients with osteosarcoma, and (2) if there is a relationship between Glut-1 expression and tumor angiogenesis. PATIENTS AND METHODS: Thirty-seven patients with resectable high-grade osteosarcomas treated between 1982 and 2007 were reviewed retrospectively. Patients were excluded if representative biopsy material and followup data were not available. The expression of Glut-1 and the number of CD34-positive microvessels for angiogenic activity were measured immunohistochemically. The median followup was 6 years 6 months (range, 11-211 months). Survival analyses were evaluated using the Kaplan-Meier method and the Cox proportional hazards model. The association between Glut-1 expression and microvessel density was analyzed using Student's t-test and chi-square test. For 12 (32.4%) of 37 patients with osteosarcoma, the expression of Glut-1 was positive, with four patients (10.8%) showing strong expression of Glut-1 protein. RESULTS: The expression of Glut-1 correlated with a shorter disease-free survival period (relative risk, 20.13; 95% CI, 1.77-229.3; p=0.0016). The microvessel density mean value of positive Glut-1 expression (mean±SD, 26.5±19.4) was lower than that of negative expression (mean±SD, 46.4±35.3; Student's t-test, p=0.038). When more than 50 was defined as a high microvessel density, positive expression of Glut-1 was significantly associated with low microvessel density (chi-square test, p=0.049). CONCLUSIONS: These findings indicate that Glut-1 is a potential predictor of survival in patients with osteosarcoma and that glucose metabolism may be negatively associated with angiogenesis. If substantiated in larger numbers of patients, these findings might stimulate the development of novel treatments for patients with a poorer prognosis. LEVEL OF EVIDENCE: Level III, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.

Exosome-formed synthetic microRNA-143 is transferred to osteosarcoma cells and inhibits their migration.

MicroRNAs (miRNAs) have emerged as potential anticancer agents, but their clinical application is limited by the lack of an effective delivery system to tumors. Exosomes are small vesicles that play important roles in intercellular communication. Here, we show that synthetic miR-143 introduced into cells is released enveloped in exosomes and that the secreted exosome-formed miR-143 is transferred to osteosarcoma cells. The delivery of exosome-formed miR-143 significantly reduced the migration of osteosarcoma cells. The delivery efficiency of exosome-formed miR-143 was less than that achieved with lipofection, but the migratory potential of osteosarcoma cells was similarly inhibited after both strategies. Our results suggest that exosomes can deliver synthetic miR-143 and are a potentially efficient and functional delivery system.

Therapeutic effect and risk factors for complications of excision in 76 patients with schwannoma.

BACKGROUND: Benign schwannoma is the most common tumor of peripheral nerves. However, the clinical course of excision and risk factors associated with postoperative neurological deficits are not well known. We evaluated the incidence of preoperative symptoms, the incidence of postoperative neurological deficits, and the risk factors of neurological deficits. METHODS: We retrospectively reviewed data of 76 patients with schwannomas treated at our institution. We reviewed the clinical characteristics, and postoperative results, and determined the possible risk factors influencing the development of complications. RESULTS: Excision of schwannoma improved the Tinel-like signs in 47 of 51 patients and spontaneous pain in 14 of 15. Eleven of 17 patients with sensory deficits showed complete recovery, but six continued to show deficits with or without improvement. Motor deficits that were observed in four patients persisted in one. New neurological deficits developed in 21 patients and persisted until final follow-up in 8. Tinel-like signs was the risk factor of surgery-related neurological deficits (p = 0.009). CONCLUSIONS: New deficits developed predominantly in patients with preoperative Tinel-like signs. Attention should be given to patients with the factor.

A novel assessment method of serum alkaline phosphatase for the diagnosis of osteosarcoma in children and adolescents.

BACKGROUND: A high serum alkaline phosphatase (ALP) level is valuable for the diagnosis of osteosarcoma in adults, but its use in teenagers is problematic because ALP levels are affected by age, gender, and pubertal stage. Because serum acid phosphatase (ACP) shows the same tetraphasic pattern as serum ALP in children and adolescents, we presumed that serum levels of ALP and ACP would have a strong correlation and that the ratio of ALP to ACP (ALP/ACP) would show little variation and would be useful for the diagnosis of osteosarcoma in teenagers. The purpose of this study was to evaluate the correlation between the serum levels of ALP and ACP and to investigate the validity of ALP/ACP in the differential diagnosis of osteosarcoma in children and adolescents. METHODS: We retrospectively examined 538 patients aged 1-18 years, including 24 with osteosarcomas, 8 with other malignant bone tumors, 56 with benign bone tumors, and with 450 non-tumor lesions (controls). We evaluated the serum levels of ALP and ACP, both obtained by preoperative examination. RESULTS: There were significant correlations between the serum ALP and ACP levels in the controls (r = 0.805 in males and r = 0.860 in females). The ratios of ALP to ACP in the controls showed little variation with age. In ROC curve analysis, to discriminate between the osteosarcomas and the controls, the cutoff levels of serum ALP and ALP/ACP were 956 (U/l) and 50.9 in males and 748 (U/l) and 43.3 in females, respectively. The sensitivity and specificity of serum ALP and ALP/ACP in the differential diagnosis of osteosarcoma were 50.0 and 89.0%, and 60.0 and 94.1%, respectively in males, and 61.5 and 72.7%, and 69.2 and 84.2%, respectively, in females. CONCLUSIONS: The results suggest that ALP/ACP is more useful than the serum ALP level in diagnosing osteosarcoma because it is little affected by the age.

Vascularized Origami Medial Femoral Condyle Flap for Finger Joint Reconstruction.

SUMMARY: Total finger joint reconstruction is challenging. Vascularized toe joint transfer is currently used for reconstruction, but it is difficult to perform, fails to achieve maximal joint flexibility, and is associated with donor-site complications. As an alternative, the authors developed a vascularized medial femoral condyle flap technique, wherein the vascularized corticoperiosteum is shaped via origami, with the donor tissue folded to fit the recipient site. In this article, the authors describe the use of this method for reconstruction of interphalangeal and metacarpophalangeal joints with a reduced range of motion. The mean age of the patients (three men and four women) was 51 years (range, 36 to 68 years), and the mean follow-up period was 3 years 1 month (range, 4 months to 5 years). In the reconstructed joints, the mean range of motion; Disabilities of the Arm, Shoulder, and Hand score; and pinch strength of the unaffected side were 55 degrees (range, 24 to 90 degrees), 2.3 (range, 0 to 6), and 98% (range, 70% to 38%), respectively. No donor-site morbidities were observed. Radiography and computed tomography scans revealed joint-like grafted tissue remodeling. The study findings suggest that the origami medial femoral condyle flap is useful for functional finger joint reconstruction. The procedure requires fabrication before grafting, but tissue harvest is relatively easy.

Physical Signs and Clinical Features of Cervical Myelopathy in Elderly Patients, Especially 80 Years or Older: Comparison of 100 Consecutive Operative Cases across Three Age Groups.

STUDY DESIGN: Retrospective cohort study. PURPOSE: The present study aimed to examine the characteristics of physical signs in elderly patients with cervical myelopathy (CM) and to compare the findings in three different age groups. OVERVIEW OF LITERATURE: As the global population ages, the incidence of CM in elderly patients is increasing. METHODS: We evaluated 100 consecutive surgical patients with CM and divided them into the following groups: 80s (34 patients; mean age, 83.9 years), 70s (33 patients; mean age, 73.9 years), and 69 or younger (33 patients; mean age, 60.9 years). The clinical symptoms and physical signs were evaluated and recorded. RESULTS: Although the recovery rate decreased with increasing age, all groups demonstrated a significant improvement in clinical symptoms relative to preoperative values. The Hoffman sign and hyperreflexia of the triceps tendon were, respectively, present in 82% and 88% of patients in the 80s group, 74% and 64% of those in the 70s group, and 69% and 82% of those in the 69 or younger group, with no significant difference among the groups. In contrast, the rates of hyperreflexia of the patellar and Achilles tendons were, respectively, 59% and 32% in the 80s group, 85% and 48% in the 70s group, and 91% and 70% in the 69 or younger group, with significant differences. CONCLUSIONS: The positivity rate of the lower extremity hyperreflexia decreased significantly with increasing age in patients with CM. The absence of hyperreflexia, particularly lower extremity, is not uncommon in elderly patients with suspected CM.

A Comparison of the Outcomes of Fiber-Wire® versus Stainless Steel Wire in Transosseous Wiring for Intra-Articular Fractures of the Distal Interphalangeal Joint.

Background: Different surgical techniques have been described for the treatment of intra-articular fractures involving extensor tendon insertion of the distal interphalangeal joint (DIPJ), including acute and chronic bony mallet injuries. We have been using transosseous stainless-steel wire (SSW) in select patients. In 2015, we started using a non-absorbable polyester suture (2-0 Fiber-Wire®, Arthrex, Naples, FL, USA) instead of SSWs. The aim of this study is to compare the outcomes of SSW and Fiber-Wire® (FBW) in transosseous wiring for intra-articular fractures of the DIPJ. Methods: This is a retrospective review of patients who underwent fixation of intra-articular fractures, including extensor tendon insertion of the DIPJ using a transosseous wiring technique, in the period from 2013 to 2018. SSW was used in the period from 2013 to 2014, and FBW was used from 2015 to 2018. Outcomes with regard to age, gender, time to union, range of motion at the DIPJ and complications were recorded and compared between the SSW and FBW groups. Results: Nine patients (mean age: 38 years) underwent fixation with SSW and 10 patients (mean age: 31 years) with FBW. The operative time was significantly lower in the FBW group, and all the fractures united. There were no statistically significant differences between both groups with regard to time to union or range of motion at the DIPJ. Similar complication rates were observed in both groups. Conclusions: The use of FBW in transosseous wiring for intra-articular fractures of the DIPJ can reduce operative time and provide functional results similar to that of SSWs. It can be considered as an alternative fixation technique for difficult intra-articular comminuted fractures of the DIPJ, including acute and chronic bony mallet injuries with joint subluxation. Level of Evidence: Level III (Therapeutic).

Osteoprogenitor differentiation is not affected by immunomodulatory thalidomide analogs but is promoted by low bortezomib concentration, while both agents suppress osteoclast differentiation.

We investigated the effects of bortezomib (PS-341) and immunomodulatory thalidomide analogs (immunomodulatory compounds; CC-4047, CC-6032, and CC-5013, or lenalidomide) on osteoblast and osteoclast differentiation in vitro using human mesenchymal stem cells (hMSC) to commit to osteoprogenitor cells and peripheral blood mononuclear cells (PBMCs) isolated from healthy donors, respectively. First, the concentration of bortezomib for an anti-myeloma effect was more than 1.0 nM in myeloma cells of multiple myeloma (MM) patients and more than 2.5 nM in myeloma cell lines. In contrast, anti-myeloma effects of immunomodulatory compounds on myeloma cells differed among myeloma cells and these compounds themselves. Subsequently, these agents (bortezomib; 0.5-5.0 nM, immunomodulatory compounds; 10 microM) were added to the osteoprogenitor cell culture media or the media for osteoclast differentiation. Low bortezomib concentrations (0.5 and 1.0 nM) increased ALP activity, and the delayed addition of bortezomib further increased ALP activity. Mineralized nodular formation with <2.5 nM bortezomib was not impaired. BMP2 expression on osteoprogenitor cells was found to increase in a time-dependent manner irrespective of treatment with bortezomib. On the other hand, the anti-osteoclast effect with low bortezomib concentration (< or =2.5 nM) depended on MM patients. In contrast, immunomodulatory compounds at 10 microM showed an anti-osteoclast effect without cytotoxicity to osteoblast differentiation, at which dose myeloma cells underwent apoptosis. These findings might improve the treatment strategy for MM patients without damaging BM stromal cells by combining bortezomib with immunomodulatory compounds.

Efficacy of a nitrogen-containing bisphosphonate, minodronate, in conjunction with a p38 mitogen activated protein kinase inhibitor or doxorubicin against malignant bone tumor cells.

PURPOSE: We recently reported the sarcoma-selective antitumor effects of a newly developed nitrogen-containing bisphosphonate, minodronate (MIN), on malignant bone tumors. The aim of this study was to develop efficient combination MIN therapy in malignant bone tumors. METHODS: We examined downstream molecular events of MIN in osteosarcoma and Ewing's sarcoma cells to search for a partner to combine with MIN. Furthermore, we evaluated the combined effects of MIN and clinically available Doxorubicin (DOX). RESULTS: We found that MIN inhibited Rap 1A prenylation, and extracellular signal-regulated kinase (ERK) or Akt phosphorylation in osteosarcoma (Saos-2) and Ewing's sarcoma (SK-ES-1) cells. Interestingly, MIN activated p38 mitogen activated protein kinase (MAPK) only in SK-ES-1 cells and a p38 MAPK inhibitor augmented MIN-induced growth inhibition in SK-ES-1 cells. Doxorubicin (DOX) exerted synergistic effects on Saos-2 and SK-ES-1 cell lines. Daily injection of MIN enhanced the growth inhibition of SK-ES-1 xenograft sarcoma treated by DOX in nude mice. CONCLUSIONS: These findings suggest that the inhibition of the p38 MAPK pathway may be attractive in overcoming cellular resistance against MIN. In the light of clinical settings, MIN may have a beneficial adjuvant role in the DOX treatment.

Scalp metastasis from malignant fibrous histiocytoma of bone.

Malignant fibrous histiocytoma (MFH) of bone is a relatively rare primary malignant neoplasm and an aggressive tumor, characterized by a high frequency of local recurrence and distant metastasis. The most common metastatic site is the lung (>80%), followed by bone and regional lymph node. Metastasis to other sites is extremely rare. In this report, we describe the skin as being the initial metastatic site for MFH of bone. A 42-year-old female presented with a bone tumor involving the right proximal tibia. She underwent tumor excision and knee joint reconstruction. Histologic examination confirmed a striform-pleomorphic type of MFH of bone. Six months postoperatively, the patient developed a scalp metastasis. Wide local excision was performed. Six months after the scalp operation, the patient was alive with no further relapse. We should keep the skin in mind as the possible initial site of metastatic MFH of bone.

Low-grade myofibroblastic sarcoma of the palm.

We report here a case of an unusual spindle cell tumour of the palm with myofibroblastic differentiation, which was surgically excised. Histologically and immunohistochemically, it was a low-grade myofibroblastic sarcoma. After 25 months follow-up the patient is well and free of recurrence.

Clinical outcomes of limb salvage surgery with postoperative intensity-modulated radiation therapy for soft-tissue sarcoma and metastasis.

OBJECTIVE: The primary aim of intensity-modulated radiation therapy (IMRT) for treating soft tissue sarcoma of an extremity is the reduction of morbidity and maintenance of local control. METHODS: We evaluated the outcomes and toxicity of adjuvant IMRT following function-preserving surgery to treat patients with soft tissue sarcoma and metastasis of the extremities. We retrospectively reviewed prospective databases at Kure Medical Center and Aichi Medical University between 2013 and 2016 and identified 10 patients with lower extremity soft tissue sarcoma who underwent both limb-sparing surgery and postoperative IMRT at one of our institutions. RESULTS: There were 7 men and 3 women (mean age, 67.2 years; range, 48-87 years) included in the study. Of these, four patients were continuously disease-free, two showed no evidence of disease, and four died due to disease. The average functional score was 82% (range, 53-100%). Among the 10 patients, 2 (22%) had grade 1-2 edema and 1 (11%) had grade 2 joint stiffness. Another patient developed grade 2 acute dermatitis. There were no severe complications such as infection, tissue necrosis, fracture, or nerve palsy. CONCLUSION: Although the number of patients in this study was small, our results show that adjuvant IMRT following function-preserving surgery for soft tissue sarcoma of the extremity can be valuable for treating unmanageable tumors.

Telomere length and telomerase activity in extra-abdominal desmoid tumors.

The telomere biology of extra-abdominal desmoids was investigated. In 12 specimens, telomere length was assessed by Southern-blot analysis and telomerase activity was measured using a PCR-based TRAP assay. There was a significant correlation between telomere length and tumor size, with telomeres being shorter with increasing tumor size (p = 0.049), and between telomere length and PCNA-positive cell rate, with telomere shortening with increased positive cell rate (p = 0.017). There was a significant correlation between telomerase activity and age at surgery, with increased activity with younger age (p = 0.015). Telomere length increased with recurrence, but telomerase activity decreased, and rate of PCNA-positive cells became lower, whenever the tumors were recurrent. Decreasing telomere length correlated with tumor size, probably due to increased duration of proliferation in the tumor, and tumor aggressiveness. Recurrent case results may be due to a lower rate of cell division and the presence of telomerase activity.

Conservative surgery for well-differentiated liposarcomas of the extremities adjacent to major neurovascular structures.

BACKGROUND: There is no clear consensus as to the appropriate nomenclature and the best surgical strategy for well-differentiated liposarcomas. A wide surgical excision is recommended over marginal resection for local control of well-differentiated liposarcomas. However, this surgical procedure should be reconsidered for lesions, which come into contact with major neurovascular structures. METHODS: Between 1998 and 2004, 12 well-differentiated liposarcomas of the extremities were treated at our institute. Among them, nine lesions (75%) adjacent to major nerves or blood vessels were marginally resected with careful dissection of these critical structures. The clinical outcomes were reviewed for a mean follow-up time of 4 years. RESULTS: Seven patients continued to be disease-free without any loss of limb function. One patient developed a local recurrence 30 months postoperatively. The other patient with a foot lesion involving the fourth metatarsal bone has experienced slight difficulty in gait-balancing due to the fourth toe amputation, but remains free of disease. The local control rate was 88.9%, even though seven lesions were resected with positive surgical margins. CONCLUSIONS: Our findings suggested that well-differentiated liposarcomas frequently arise in close proximity to major nerves or blood vessels. Marginal resection alone seems to be adequate for these lesions to preserve critical structures.

Inhibitory effects of a new bisphosphonate, minodronate, on proliferation and invasion of a variety of malignant bone tumor cells.

Little is known about the biological effects of bisphosphonates on primary malignant bone tumors. The purpose of this study was to investigate the antitumor effects of newly developed minodronate (MIN) on a variety of human malignant bone tumors. We examined the effects of MIN and clinically relevant incadronate (INC) on the proliferation, apoptosis, and cell cycle of two osteosarcoma (Saos-2, MG-63), two chondrosarcoma (SW1353, OUMS27), and two Ewing's sarcoma (RD-ES, SK-ES-1) cell lines. Furthermore, we investigated the anti-invasion effects of MIN on sarcoma cells and the effects of MIN on tumor growth in nude mice. MIN inhibited the viability of all six cell lines in a dose-dependent manner with IC50 values of 2.7 to 5.0 microM, which were significantly lower than those of INC. Importantly, both bisphosphonates affected the viability of normal bone marrow stromal cells much less than sarcoma cells. Both bisphosphonates induced cell cycle perturbation in all sarcoma cells tested and apoptosis in Saos-2 and SW1353 cells, although they failed to induce apoptosis in RD-ES and SK-ES-1 cells. MIN significantly suppressed invasion, even at a low concentration of 1 microM (p < 0.01). Daily injection of 5 microg of MIN inhibited the growth of SK-ES-1 xenograft sarcoma in nude mice without loss of body weight. These findings suggest that MIN may have a beneficial adjuvant role in the treatment of patients with malignant bone tumors.

Nerve tolerance to high-dose-rate brachytherapy in patients with soft tissue sarcoma: a retrospective study.

BACKGROUND: Brachytherapy, interstitial tumor bed irradiation, following conservative surgery has been shown to provide excellent local control and limb preservation in patients with soft tissue sarcomas (STS), whereas little is known about the tolerance of peripheral nerves to brachytherapy. In particular, nerve tolerance to high-dose-rate (HDR) brachytherapy has never been properly evaluated. In this study, we examined the efficacy and radiation neurotoxicity of HDR brachytherapy in patients with STS in contact with neurovascular structures. METHODS: Between 1995 and 2000, seven patients with STS involving the neurovascular bundle were treated in our institute with limb-preserving surgery, followed by fractionated HDR brachytherapy. Pathological examination demonstrated that 6 patients had high-grade lesions with five cases of negative margins and one case with positive margins, and one patient had a low-grade lesion with a negative margin. Afterloading catheters placed within the tumor bed directly upon the preserved neurovascular structures were postoperatively loaded with Iridium-192 with a total dose of 50 Gy in 6 patients. One patient received 30 Gy of HDR brachytherapy combined with 20 Gy of adjuvant external beam radiation. RESULTS: With a median follow-up of 4 years, the 5-year actuarial overall survival, disease-free survival, and local control rates were 83.3, 68.6, and 83.3%, respectively. None of the 7 patients developed HDR brachytherapy-induced peripheral neuropathy. Of 5 survivors, 3 evaluable patients had values of motor nerve conduction velocity of the preserved peripheral nerve in the normal range. CONCLUSION: In this study, there were no practical and electrophysiological findings of neurotoxicity of HDR brachytherapy. Despite the small number of patients, our encouraging results are valuable for limb-preserving surgery of unmanageable STS involving critical neurovascular structures.