Coefficient of variation of T2-weighted MRI may predict the prognosis of malignant peripheral nerve sheath tumor.

BACKGROUND: We investigated whether non-enhancement MRI features, including measurement of the heterogeneity of the tumor with MR T2 imaging by calculating coefficient of variation (CV) values, were associated with the prognosis of non-metastatic malignant peripheral nerve sheath tumors (MPNST). METHODS: This retrospective study included 42 patients with MPNST who had undergone surgical resection (mean age, 50 years ± 21; 20 male participants). Non-enhancement MR images were evaluated for signal intensity heterogeneity on T1- and T2-weighted imaging, tumor margin definition on T1- and T2-weighted imaging, peritumoral edema on T2-weight imaging, and CV. We measured the signal intensities of MR T2-weighted images and calculated the corresponding CV values. CV is defined as the ratio of the standard deviation to the mean. The associations between factors and overall survival (OS) were investigated via the Kaplan-Meier method with log-rank tests and the Cox proportional hazards model. RESULTS: The mean CV value of MR T2 images was 0.2299 ± 0.1339 (standard deviation) (range, 0.0381-0.8053). Applying receiver operating characteristics analysis, the optimal cut-off level for CV value was 0.137. This cut-off CV value was used for its stratification into high and low CV values. At multivariate survival analysis, a high CV value (hazard ratio = 3.63; 95% confidence interval = 1.16-16.0; p = 0.047) was identified as an independent predictor of OS. CONCLUSION: The CV value of the signal intensity of heterogenous MPNSTs MR T2-weighted images is an independent predictor of patients' OS.

Comparison of clinical outcome between surgical treatment and particle beam therapy for pelvic bone sarcomas: A retrospective multicenter study in Japan.

BACKGROUND: Few studies have compared the clinical outcomes of patients with pelvic bone sarcomas treated surgically and those treated with particle beam therapy. This is a multicenter retrospective cohort study which compared the clinical outcomes of patients with pelvic bone sarcoma who underwent surgical treatment and particle beam therapy in Japan. METHODS: A total of 116 patients with pelvic bone sarcoma treated at 19 specialized sarcoma centers in Japan were included in this study. Fifty-seven patients underwent surgery (surgery group), and 59 patients underwent particle beam therapy (particle beam group; carbon-ion radiotherapy: 55 patients, proton: four patients). RESULTS: The median age at primary tumor diagnosis was 52 years in the surgery group and 66 years in the particle beam group (P < 0.001), and the median tumor size was 9 cm in the surgery group and 8 cm in the particle beam group (P = 0.091). Overall survival (OS), local control (LC), and metastasis-free survival (MFS) rates were evaluated using the Kaplan-Meier method and compared among 116 patients with bone sarcoma (surgery group, 57 patients; particle beam group, 59 patients). After propensity score matching, the 3-year OS, LC, and MFS rates were 82.9% (95% confidence interval [CI], 60.5-93.2%), 66.0% (95% CI, 43.3-81.3%), and 78.4% (95% CI, 55.5-90.5%), respectively, in the surgery group and 64.9% (95% CI, 41.7-80.8%), 86.4% (95% CI, 63.3-95.4%), and 62.6% (95% CI, 38.5-79.4%), respectively, in the particle beam group. In chordoma patients, only surgery was significantly correlated with worse LC in the univariate analysis. CONCLUSIONS: The groups had no significant differences in the OS, LC, and MFS rates. Among the patients with chordomas, the 3-year LC rate in the particle beam group was significantly higher than in the surgery group.

What Are the Complications, Function, and Survival of Tumor-devitalized Autografts Used in Patients With Limb-sparing Surgery for Bone and Soft Tissue Tumors? A Japanese Musculoskeletal Oncology Group Multi-institutional Study.

BACKGROUND: Tumor-devitalized autografts treated with deep freezing, pasteurization, and irradiation are biological reconstruction methods after tumor excision for aggressive or malignant bone or soft tissue tumors that involve a major long bone. Tumor-devitalized autografts do not require a bone bank, they carry no risk of viral or bacterial disease transmission, they are associated with a smaller immunologic response, and they have a better shape and size match to the site in which they are implanted. However, they are associated with disadvantages as well; it is not possible to assess margins and tumor necrosis, the devitalized bone is not normal and has limited healing potential, and the biomechanical strength is decreased owing to processing and tumor-related bone loss. Because this technique is not used in many countries, there are few reports on the results of this procedure such as complications, graft survival, and limb function. QUESTIONS/PURPOSES: (1) What was the rate of complications such as fracture, nonunion, infection, or recurrence in a tumor-devitalized autograft treated with deep freezing, pasteurization, and irradiation, and what factors were associated with the complication? (2) What were the 5-year and 10-year grafted bone survival (free from graft bone removal) of the three methods used to devitalize a tumor-containing autograft, and what factors were associated with grafted bone survival? (3) What was the proportion of patients with union of the tumor-devitalized autograft and what factors were associated with union of the graft-host bone junction? (4) What was the limb function after the tumor-devitalized autograft, and what factors were related to favorable limb function? METHODS: This was a retrospective, multicenter, observational study that included data from 26 tertiary sarcoma centers affiliated with the Japanese Musculoskeletal Oncology Group. From January 1993 to December 2018, 494 patients with benign or malignant tumors of the long bones were treated with tumor-devitalized autografts (using deep freezing, pasteurization, or irradiation techniques). Patients who were treated with intercalary or composite (an osteoarticular autograft with a total joint arthroplasty) tumor-devitalized autografts and followed for at least 2 years were considered eligible for inclusion. Accordingly, 7% (37 of 494) of the patients were excluded because they died within 2 years; in 19% (96), an osteoarticular graft was used, and another 10% (51) were lost to follow-up or had incomplete datasets. We did not collect information on those who died or were lost to follow-up. Considering this, 63% of the patients (310 of 494) were included in the analysis. The median follow-up was 92 months (range 24 to 348 months), the median age was 27 years (range 4 to 84), and 48% (148 of 310) were female; freezing was performed for 47% (147) of patients, pasteurization for 29% (89), and irradiation for 24% (74). The primary endpoints of this study were the cumulative incidence rate of complications and the cumulative survival of grafted bone, assessed by the Kaplan-Meier method. We used the classification of complications and graft failures proposed by the International Society of Limb Salvage. Factors relating to complications and grafted autograft removal were analyzed. The secondary endpoints were the proportion of bony union and better limb function, evaluated by the Musculoskeletal Tumor Society score. Factors relating to bony union and limb function were also analyzed. Data were investigated in each center by a record review and transferred to Kanazawa University. RESULTS: The cumulative incidence rate of any complication was 42% at 5 years and 51% at 10 years. The most frequent complications were nonunion in 36 patients and infection in 34 patients. Long resection (≥ 15 cm) was associated with an increased risk of any complication based on the multivariate analyses (RR 1.8 [95% CI 1.3 to 2.5]; p < 0.01). There was no difference in the rate of complications among the three devitalizing methods. The cumulative graft survival rates were 87% at 5 years and 81% at 10 years. After controlling for potential confounding variables including sex, resection length, reconstruction type, procedure type, and chemotherapy, we found that long resection (≥ 15 cm) and composite reconstruction were associated with an increased risk of grafted autograft removal (RR 2.5 [95% CI 1.4 to 4.5]; p < 0.01 and RR 2.3 [95% CI 1.3 to 4.1]; p < 0.01). The pedicle freezing procedure showed better graft survival than the extracorporeal devitalizing procedures (94% versus 85% in 5 years; RR 3.1 [95% CI 1.1 to 9.0]; p = 0.03). No difference was observed in graft survival among the three devitalizing methods. Further, 78% (156 of 200 patients) of patients in the intercalary group and 87% (39 of 45 patients) of those in the composite group achieved primary union within 2 years. Male sex and the use of nonvascularized grafts were associated with an increased risk of nonunion (RR 2.8 [95% CI 1.3 to 6.1]; p < 0.01 and 0.28 [95% CI 0.1 to 1.0]; p = 0.04, respectively) in the intercalary group after controlling for confounding variables, including sex, site, chemotherapy, resection length, graft type, operation time, and fixation type. The median Musculoskeletal Tumor Society score was 83% (range 12% to 100%). After controlling for confounding variables including age, site, resection length, event occurrence, and graft removal, age younger than 40 years (RR 2.0 [95% CI 1.1 to 3.7]; p = 0.03), tibia (RR 6.9 [95% CI 2.7 to 17.5]; p < 0.01), femur (RR 4.8 [95% CI 1.9 to 11.7]; p < 0.01), no event (RR 2.2 [95% CI 1.1 to 4.5]; p = 0.03), and no graft removal (RR 2.9 [95% CI 1.2 to 7.3]; p = 0.03) were associated with an increased limb function. The composite graft was associated with decreased limb function (RR 0.4 [95% CI 0.2 to 0.7]; p < 0.01). CONCLUSION: This multicenter study revealed that frozen, irradiated, and pasteurized tumor-bearing autografts had similar rates of complications and graft survival and all resulted in similar limb function. The recurrence rate was 10%; however, no tumor recurred with the devitalized autograft. The pedicle freezing procedure reduces the osteotomy site, which may contribute to better graft survival. Furthermore, tumor-devitalized autografts had reasonable survival and favorable limb function, which are comparable to findings reported for bone allografts. Overall, tumor-devitalized autografts are a useful option for biological reconstruction and are suitable for osteoblastic tumors or osteolytic tumors without severe loss of mechanical bone strength. Tumor-devitalized autografts could be considered when obtaining allografts is difficult and when a patient is unwilling to have a tumor prosthesis and allograft for various reasons such as cost or socioreligious reasons. LEVEL OF EVIDENCE: Level III, therapeutic study.

Local surgery feasibility and safety after carbon ion radiotherapy for primary bone sarcomas.

BACKGROUND: It is known that several complications are caused by local surgery after radiotherapy. Clinical reports that describe the postoperative complications associated with surgery after carbon ion radiotherapy are sparse. This study aimed to elucidate local surgery feasibility after carbon ion radiotherapy specifically for primary bone sarcomas. METHODS: The medical, surgical, and irradiation records of patients who had local surgery at the area irradiated with carbon ion beams between 2004 and 2018 were reviewed retrospectively to evaluate the feasibility and indication of local surgery after CIRT. RESULTS: There were eight patients who had 10 local surgeries at the irradiated sites among the 42 carbon ion radiotherapy patients. There were seven males and one female with a median age of 50 years (range 26-73 years). The reasons for surgery were three for skin toxicity and associated infection, five for bone collapse, and associated implant failure, and two for tumor regrowth. All surgical fields included the area of more than 60 Gy (RBE) irradiated dose. All three surgical cases caused by skin toxicity and associated infection had Grade I wound complication after surgery according to the Clavien-Dindo Classification. CONCLUSION: Local surgery after CIRT appeared feasible in selected patients with primary bone sarcoma, especially for the patients with bone collapse and associated implant failure. However, infection and prescribed irradiation dose at the incision site must be carefully evaluated.

Perioperative Adriamycin plus ifosfamide vs. gemcitabine plus docetaxel for high-risk soft tissue sarcomas: randomised, phase II/III study JCOG1306.

BACKGROUND: This randomised phase II/III trial aimed to determine whether perioperative chemotherapy with gemcitabine plus docetaxel (GD) is non-inferior to the standard Adriamycin plus ifosfamide (AI) in terms of overall survival (OS) in patients with soft tissue sarcoma (STS). METHODS: Patients with localised high-risk STS in the extremities or trunk were randomised to receive AI or GD. The treatments were repeated for three preoperative and two postoperative courses. The primary endpoint was OS. RESULTS: Among 143 enrolled patients who received AI (70 patients) compared to GD (73 patients), the estimated 3-year OS was 91.4% for AI and 79.2% for GD (hazard ratio 2.55, 95% confidence interval: 0.80-8.14, P = 0.78), exceeding the prespecified non-inferiority margin in the second interim analysis. The estimated 3-year progression-free survival was 79.1% for AI and 59.1% for GD. The most common Grade 3-4 adverse events in the preoperative period were neutropenia (88.4%), anaemia (49.3%), and febrile neutropenia (36.2%) for AI and neutropenia (79.5%) and febrile neutropenia (17.8%) for GD. CONCLUSIONS: Although GD had relatively mild toxicity, the regimen-as administered in this study-should not be considered a standard treatment of perioperative chemotherapy for high-risk STS in the extremities and trunk. CLINICAL TRIAL REGISTRATION: jRCTs031180003.

Impact of surgical resection on survival in patients with metastatic soft tissue sarcoma and comparison between synchronous and metachronous metastases.

BACKGROUND: The role of local surgery in patients with metastatic soft tissue sarcoma (STS) remains unknown. The study aims to assess the clinical outcomes and impact of surgical resection on survival in patients with metastatic STS and elucidate the survival differences between synchronous and metachronous metastatic groups. METHODS: Among the 272 patients with STS treated between 2000 and 2018, 84 with synchronous or metachronous metastasis were included. Associations between overall survival and primary tumor resection and metastasectomy were assessed using multivariate Cox regression analyses to adjust for baseline differences between surgically and non-surgically treated patients. Propensity score matching was applied to compare synchronous and metachronous metastasis. RESULTS: Among the 84 patients included, 69 (82%) and 41 (49%) underwent primary tumor resection and metastasectomy, respectively. The 2- and 5-year overall survivals of all patients after first detection of metastasis were 51.1% and 24.4%, respectively. Multivariate analysis showed that size <8 cm, grade <3, and number of metastases <4 were associated with longer overall survival. After adjusting for baseline demographic and tumor characteristics, primary tumor resection and metastasectomy still had favorable effects on survival. Tumor subtypes, grade, and number of metastases differed significantly between synchronous and metachronous groups. However, after adjusting for these valuables, both groups exhibited comparable survival. CONCLUSIONS: Approximately one fourth of the patients with metastatic STS survived for >5 years. Our results showed that surgical resection of primary tumors or metastatic lesions had favorable impact on survival even after adjusting for patient backgrounds, with comparable survival observed between those with synchronous and metachronous metastases.

Clinical Outcomes of Patients with Metastatic Solitary Fibrous Tumors: A Japanese Musculoskeletal Oncology Group (JMOG) Multiinstitutional Study.

BACKGROUND: Although the unpredictable malignant behavior of solitary fibrous tumors (SFTs) has been recognized, the clinical features and prognosis of metastatic SFTs have not been well documented due to the extreme rarity of these cases. The aim of this study is to investigate the clinical features, prognostic factors, and optimal management of patients with metastatic SFTs. PATIENTS AND METHODS: Sixty patients with metastatic SFT were retrospectively reviewed. Univariate and multivariate analyses were performed to identify the factors associated with survival. Time to next treatment (TNT) was used to evaluate the effects of various chemotherapy regimens. RESULTS: A total of 34 male and 26 female patients (median age 55 years, range, 23-87 years) were included in the study. The median follow-up period after metastasis was 32 months (range 1-126 months). Tumor location and local recurrence were correlated with late metastasis. The 3- and 5-year overall survival rates were 72.7% and 49.2%, respectively. Primary tumor location, number of metastases, and metastasectomy were significantly associated with survival. Metastasectomy was the only significant variable on multivariate analysis. The TNT was significantly different among the various regimens. CONCLUSIONS: Patients with metastatic SFTs had relatively longer survival periods compared with those with other metastatic soft-tissue sarcomas. Tumor location and number of metastases was associated with survival. Surgical resection of the metastatic lesions offers the best chance of survival, however further studies are warranted to define patients who would benefit from metastasectomy, and the most effective chemotherapeutic regimen for patients with metastatic SFTs remains unknown.

Efficacy and safety of TAS-115, a novel oral multi-kinase inhibitor, in osteosarcoma: an expansion cohort of a phase I study.

Background osteosarcoma is a rare, primary malignant bone tumour with limited available treatments for advanced or recurrent disease, resulting in a poor prognosis for patients. TAS-115 is a novel tyrosine kinase inhibitor under investigation in a phase I study in patients with solid tumours. We report data of osteosarcoma patients in the expansion cohort of this ongoing study. Patients and methods an analysis of this multicentre, open-label study was performed 6 months after the final patient was enrolled, and included patients aged ≥15 years, with unresectable or recurrent osteosarcoma, and who had refractory to standard therapy or for whom no standard therapy was available. TAS-115 650 mg/day was orally administered in a 5 days on/2 days off schedule. Results a total of 20 patients with osteosarcoma were enrolled. The most common adverse drug reactions (ADRs) were neutrophil count decreased (75%), aspartate aminotransferase increased (50%), and platelet count decreased (50%); 85% of patients had grade ≥ 3 ADRs. Long-term disease control (>1 year) with TAS-115 was achieved in three patients. The best overall response was stable disease (50%); no patient achieved a complete or partial response. Median progression-free survival was 3 months; 4-month and 12-month progression-free rates were 42% and 31%, respectively. Conclusion the safety and tolerability of TAS-115 and long-term disease stability for patients with unresectable or recurrent osteosarcoma were confirmed in this study, suggesting that TAS-115 is a promising novel therapy for advanced osteosarcoma patients. Trial registration number: JapicCTI-132333 (registered on November 8, 2013).

Giant cell tumor of bone - Analysis of 213 cases involving extra-craniofacial bones.

We elucidated clinicopathological characteristics of giant cell tumor of bone (GCTB) in Japan, and significant clinicopathological factors for predicting local recurrence. Clinicopathological profiles of 213 patients with GCTB (100 male, 113 female) involving extra-craniofacial bones were retrieved. Pathological slides obtained at the initial surgery were reviewed. Fourteen pathological and five clinical features were statistically analyzed to disclose prognostic significance. Patient age ranged from 12-80 years (Average 38.7). Long bones were most frequently affected (86.4%), especially around the knee (62.9%). Histological features are basically similar to those previously reported. Within a follow-up period (24-316 months, average 106.1 months), the local recurrence rate is 29.1%. Metastasis has occurred in 9 patients. Cox regression analysis of representative clinicopathological features shows that younger age, higher mitotic count, smaller zones of stromal hemorrhage, considerable vascular invasion and absence of ischemic necrosis are significant predictors for local recurrence. Initial operative method (curettage) is a significant risk factor in univariate analysis but not by multivariate analysis (P = 0.053). Denosumab administration increases risk but not significantly (P = 0.053). Histone 3.3 G34W immunopositivity is not significant for predicting local recurrence.

Complication rate, functional outcomes, and risk factors associated with carbon ion radiotherapy for patients with unresectable pelvic bone sarcoma.

BACKGROUND: To the authors' knowledge, carbon ion radiotherapy (CIRT) is one of the few curative treatments for unresectable pelvic bone sarcoma. The current study investigated the complications, functional outcomes, and risk factors of CIRT. METHODS: Of 112 patients who were treated with CIRT for unresectable pelvic bone sarcoma, the authors enrolled 29 patients who were without local disease recurrence or distant metastasis. The mean follow-up was 93 months. Complications, functional outcomes, and quality of life scores were assessed. Risk factors were analyzed, including the dose-volume histogram of the femoral head. RESULTS: Femoral head necrosis occurred in approximately 37% of patients, pelvic fractures were reported in 48% of patients, and neurological deficits were noted in 52% of patients. Femoral head necrosis was found to be significantly more prevalent among patients with periacetabular tumors (P = .018). The dose-volume histogram of the femoral head indicated tolerable volume percentages of the femoral head to be <33% for 40 grays (relative biological effectiveness) and 16% for 60 grays ( relative biological effectiveness). The mean Musculoskeletal Tumor Society score and Toronto Extremity Salvage Score were 53% and 64%, respectively, and the mean EuroQol 5 dimensions questionnaire index was 0.587. Patients aged >50 years and those with periacetabular tumors were found to have significantly lower Toronto Extremity Salvage Scores. CONCLUSIONS: Femoral head necrosis, pelvic fracture, and nerve damage are common complications with the use of CIRT for pelvic bone sarcoma. To prevent femoral head necrosis, the radiation dose to the femoral head should be kept below the estimated tolerance curve presented in the current study. The functional outcome is nearly equivalent to that of surgery. CIRT may be a promising alternative to surgery for patients with unresectable pelvic bone sarcoma.

A long-term follow-up study of extracorporeal irradiated autografts in limb salvage surgery for malignant bone and soft tissue tumors: A minimum follow-up of 10 years after surgery.

BACKGROUND AND OBJECTIVES: The aim of this study is to assess the survival, function, radiographic appearance, and modes of failure of extracorporeal irradiated (ECI) autografts in a long-term setting. METHODS: We retrospectively reviewed 87 patients who were treated for bone and soft tissue tumors using ECI autografts between 1988 and 2009. RESULTS: The 56 patients had a minimum follow-up of 10 years, and the median follow-up period was 16.5 years. The reimplantation procedures included 24 osteoarticular grafts, 16 intercalary grafts, 10 autograft-prosthetic composite grafts, and 6 hemicortical grafts. The 15-year graft and event-free survival rates were 76.8% and 47.9%, respectively. Infection and structural failure were the most common reasons for additional surgery. The time for additional surgery was significantly longer in patients with composite grafts (P < .01). The median Musculoskeletal Tumor Society score and the International Society of Limb Salvage score were 80% and 84%, respectively. CONCLUSIONS: ECI autografts are a durable option for reconstruction after resection of musculoskeletal tumors and provide good function over more than 15 years. Most graft failures occurred within 5 years of the index surgery. However, composite grafts showed a tendency to fail more than 10 years after the surgery.

Clinical outcomes of chondroblastoma treated using synthetic bone substitute: risk factors for developing radiographic joint degeneration.

BACKGROUND: Chondroblastoma (CB) is a rare locally aggressive bone tumor that commonly occurs in the epiphysis or apophysis of long bones. Although surgical treatment of CB carries potential risk for physeal or articular cartilage damage, risk factors for joint degeneration have not been well described. In addition, we have mainly used synthetic bone substitute (SBS) to fill the bone defect after intralesional curettage as treatment for CB. This study thus aimed to evaluate the incidence of and risk factors for adjacent-joint radiographic degeneration after SBS treatment for CB. METHODS: We retrospectively reviewed 48 patients treated for CB at our institutions between 1996 and 2017. Clinical data, radiographic images, treatments, and local recurrence were analyzed. RESULTS: We identified 40 patients [29 males and 11 females with a mean age of 19 years (range, 8-35 years)] who received SBS to fill the defect after curettage with a minimum follow-up of 1 year. The mean follow-up period was 71 months (range, 13-239 months). A total of 8 patients (20%) developed local recurrence. Radiographic analysis showed that 5 patients (16.7%) developed radiographic joint degeneration. Joint degeneration was significantly associated with the affected joint (p = 0.004). CONCLUSIONS: Curettage and SBS filling had been found to be a reasonable treatment method for CB, which commonly occurs in the epiphysis or apophysis. Radiographic joint degeneration was not uncommon after CB treatment, especially in the talus and proximal humerus.

Localized synovial sarcoma: A single institutional study of 191 patients with a minimum follow-up of 5 years for survivors.

PURPOSE: Factors affecting long-term outcomes of synovial sarcoma (SS) remain unknown. Here, we aimed to investigate the long-term oncological outcomes and prognostic factors in a large group of patients with surgically-treated localized SS. PATIENTS AND METHODS: Between 1980 and 2011, 191 patients (94 males and 97 females) were treated at a single hospital with a minimum follow-up of 5 years for survivors. The median age was 35 years (range, 3-80 years), and the median follow-up period was 83 months (range, 3-235 months). RESULTS: Disease-specific survival was 76.4% and 60.4% at 5 and 10 years, respectively. Local recurrence occurred in 23 patients at a median of 33 months (range, 6-158 months), and metastasis occurred in 73 patients at a median of 20 months (range, 2-166 months). In multivariate analysis, grade 3 tumors sized ≥5 cm were significantly associated with worse survival. Ten patients (5.2%) developed metastasis more than 5 years after surgery. CONCLUSION: Tumor size and grade govern prognosis in surgically-treated localized SS in long-term settings. If adequately treated patients have not developed metastases for 5 years after surgery, the risk of subsequently developing metastases was lower than previously reported.

Long-term outcomes and prognostic factors of pulmonary metastasectomy for osteosarcoma and soft tissue sarcoma.

BACKGROUND: The prognostic factors of pulmonary metastasectomy in patients with osteosarcoma and soft tissue sarcoma remain controversial. The purpose of our analysis was to explore the prognostic factors and outcomes of patients with osteosarcoma and soft tissue sarcoma who underwent pulmonary metastasectomy at our institution. METHODS: We reviewed the data of 44 patients who underwent resection of pulmonary metastases from 1996 to 2016 at our institution. The Kaplan-Meier method, log-rank test and multivariate Cox hazard model were used for comparison and survival analyses. RESULTS: There was no perioperative mortality. The median post-metastasectomy overall survival was 24.8 months, and the 5-year overall survival rate of all patients was 43.5%. The 5-year survival rate of the patients who underwent repeat thoracotomies was 60.0%. Incomplete resection, a largest tumor size > 2 cm and a disease-free interval < 12 months were associated with poor survival in multivariate analyses. Among eight patients, who underwent repeat pulmonary resection, two remain alive with no evidence of disease. These patients had the longest DFI and DFI-2 (time from first pulmonary metastasectomy to the diagnosis of recurrent pulmonary metastasis), respectively. CONCLUSION: The survival of patients with a relatively long disease-free interval, small tumor size and complete resection was favorable following the treatment of osteosarcoma and soft tissue sarcoma with pulmonary metastasectomy. Repeat pulmonary metastasectomies also provide favorable prognosis in select patients.

Prognostic implication of adjuvant/neoadjuvant chemotherapy consisting of doxorubicin and ifosfamide in patients with extraskeletal osteosarcoma.

BACKGROUND: Extraskeletal osteosarcoma (ESOS) is an extremely rare soft tissue sarcoma. Their prognosis remains poor. Our purposes were to identify the effective chemotherapeutic regimen for ESOS. METHODS: We retrospectively reviewed 16 patients with ESOS treated at the Osaka University Orthopaedic Oncology Group between 1992 and 2012. We extracted the clinical data on patients. Kaplan-Meier method and the log-rank test were used for survival analyses. RESULTS: Median age of the patients was 61.5 years (range 25-79 years). Wide local excision was performed for 11 patients and 9 patients were treated combined with chemotherapy. The 5-year disease-specific survival (DSS) rate was 53.9%. The 5-year DSS rates for patients treated with adjuvant/neoadjuvant chemotherapy or not were 66.7% or 25%, respectively (p = 0.0215). Furthermore, the 5-year DSS rates for patients treated with adjuvant/neoadjuvant chemotherapy consisting of doxorubicin and ifosfamide and those treated with other regimens were 100% or 40%, respectively (p = 0.0327). CONCLUSION: The present study demonstrated that adjuvant/neoadjuvant chemotherapy, especially consisting of doxorubicin and ifosfamide, was potentially efficacious for ESOS. Further prospective study using this multimodality treatment approach to patients with ESOS should be strongly warranted.

Is the Width of a Surgical Margin Associated with the Outcome of Disease in Patients with Peripheral Chondrosarcoma of the Pelvis? A Multicenter Study.

BACKGROUND: We attempted to resect peripheral chondrosarcoma of the pelvis with clear margins. Because of the proximity of vessels or organs, there is still concern that narrow surgical margins may have an adverse effect on disease outcomes. Although current guidelines recommend resection of histologic Grade II or Grade III chondrosarcomas with a "wide" margin, there are no specific recommendations for the adequate width of a surgical margin. QUESTIONS/PURPOSES: (1) What is the disease-specific and local recurrence-free survival of patients with peripheral chondrosarcoma of the pelvis treated with resection or amputation? (2) Is the width of a surgical margin associated with the outcome of disease in patients with peripheral chondrosarcoma of the pelvis? (3) Does the histologic grade as determined with a preoperative biopsy correlate with the final grade after resection? (4) What are surgical complications in these patients? METHODS: We retrospectively reviewed records from three international collaborating hospitals. Between 1983 and 2017, we resected 262 pelvic chondrosarcomas of all types. After reviewing the pathologic reports of these patients, we included 52 patients with peripheral chondrosarcomas of the pelvis who had an osteochondroma-like lesion at the base of the tumor and a cartilage cap with malignant cells in resected specimens. To be eligible for this study, a patient had to have a minimum of 1 year of follow-up. Two patients were excluded because they had less than 1 year of follow-up, leaving 50 patients for inclusion in this study. The median follow-up duration was 7.0 years (interquartile range 2.1-10 years). The median age was 37 years (IQR 29-54 years). The ilium was the most frequently affected bone (in 36 of 50 patients; 72%). The histologic status of the surgical margin was defined as microscopically positive (0 mm), negative < 1 mm, or negative ≥ 1 mm. Thirteen of the 50 patients (26%) had local recurrence. Seven of 34 patients had Grade I tumors, five of 13 had Grade II tumors, and one of three had a Grade III tumor. Nine of 16 patients had multiple local recurrences. Two patients with Grade I tumors and two with Grade II tumors died because of pressure effects caused by local recurrence. RESULTS: The 10-year disease-specific and local recurrence-free survival rates were 90% (95% confidence interval, 70-97) and 69% (95% CI, 52-81), respectively. A surgical margin ≥ 1 mm (n = 16) was associated with a better local recurrence-free survival rate than a surgical margin < 1 mm (n = 17) or 0 mm (n = 11) (10-year local recurrence-free survival: resection margin ≥ 1 mm = 100% versus < 1 mm = 52% [95% CI, 31 to 70]; p = 0.008). No patients with a surgical margin ≥ 1 mm had local recurrence, metastasis, or disease-related death, irrespective of tumor grade. Patients with local recurrence (n = 13) showed worse disease-specific survival than those without local recurrence (n = 37) (10-year disease-specific survival: local recurrence [+] = 59% [95% CI, 16 to 86] versus local recurrence [-] = 100%; p=0.001]). The preoperative biopsy results correctly determined the tumor grade in 15 of 41 patients (37%). The most frequent complication after surgery was local recurrence (13 of 50 patients, 26%). Deep infection was the most frequent nononcologic complication (four patients). CONCLUSIONS: We found a high local recurrence rate after surgical treatment of a peripheral pelvic chondrosarcoma, which was related to the width of the surgical margin. These local recurrences led to inoperable recurrent tumors and death. The tumor grade as determined by preoperative biopsy was inaccurate in 2/3 of patients compared with the final histologic assessment. Therefore, we believe every attempt should be made to achieve a negative margin during the initial resection to lessen the likelihood of local recurrence of peripheral chondrosarcoma of the pelvis of all grades. A margin of 1 mm or more appeared to be sufficient in these patients. LEVEL OF EVIDENCE: Level III, therapeutic study.

Clinical outcomes and significant factors in the survival rate after decompression surgery for patients who were non-ambulatory due to spinal metastases.

BACKGROUND: The development of effective chemotherapy regimens and molecular targeting agents are improving the overall survival rates in patients with cancer. However, patients who are non-ambulatory due to metastatic epidural spinal cord compression (MESCC) may be assessed as unable to tolerate chemotherapy secondary to poor performance status. This means that the ambulatory status of patients with cancer might be significant for survival time. METHODS: We investigated the functional outcomes and factors influencing overall survival in 31 patients who were non-ambulatory due to MESCC and underwent decompression surgery. The functional outcome was determined by the Frankel grading system. RESULT: Twenty-one patients (68%) improved by at least 1 Frankel grade; 17 patients (55%) became ambulatory postoperatively. Most of postoperatively ambulatory patients could undergo postoperative chemotherapy (14/17, 82%). On the other hand, only a few postoperatively non-ambulatory patients could undergo postoperative chemotherapy (2/15, 13%). We observed a complication rate of 35.5% with specific complications including wound infection, pneumonia, and deep vein thrombosis/pulmonary embolus. The median survival duration was 7.0 months. Factors that significantly affected the overall survival in univariate analyses were revised Tokuhashi score (RTS) ≥ 4, postoperative chemotherapy, ambulatory status, and complications (RTS ≥ 4, P < 0.05; postoperative chemotherapy, P < 0.001; ambulatory status, P < 0.001; complications, P < 0.01). CONCLUSIONS: Decompression surgery for patients who are non-ambulatory due to MESCC directly contributes to functional outcomes and may indirectly contribute to overall survival. If non-ambulatory patients who are assessed as unable to tolerate chemotherapy due to poor performance status regain the ability to walk by decompression surgery, they will have a chance to receive postoperative chemotherapy, thereby increasing their chances of prolonging survival. However, postoperative complications may shorten their survival; therefore, we should carefully consider the surgical indications. RTS is useful for judging the surgical indication.

Survival analysis of elderly patients with osteosarcoma.

BACKGROUND: Few studies have described the characteristics and prognostic factors of elderly patients with osteosarcoma. We retrospectively investigated clinico-pathological features and prognostic factors in osteosarcoma patients > 40 years old. METHODS: Patients with high-grade osteosarcoma > 40 years old who were treated at our institutions from 2000 to 2016 were recruited for this study. Information on patient, tumour, and treatment-related factors was collected and statistically analyzed. The median follow-up was 26.5 months (range, 5-139 months) for all patients. RESULTS: Fifty patients (30 males and 20 females) were included. The median age at diagnosis was 59.5 years (range, 41-81 years). The primary lesions were found in the limbs in 32 patients, trunk in 12, and craniofacial bones in six. Primary and secondary osteosarcoma occurred in 41 and 9 patients, respectively. Eight patients exhibited initial distant metastasis. Definitive surgery and chemotherapy were performed in 39 patients each. The rate of good responders after neoadjuvant chemotherapy was 38%. The five year overall survival (OS) rates for all patients and those without distant metastasis at diagnosis were 44.5% and 51.1%, respectively. Multivariate analysis showed that definitive surgery was the only significant prognostic factor in non-metastatic patients. The five year OS and disease-free survival (DFS) rates for non-metastatic patients who received definitive surgery were 64.3% and 60%, respectively. Among these patients, neoadjuvant and/or adjuvant chemotherapy significantly improved both OS and DFS. CONCLUSIONS: Complete surgical resection and intensive chemotherapy should be performed for osteosarcoma patients > 40 years old despite distinct clinicopathological characteristics from those of younger patients.

Clinical outcomes of patients with epithelioid sarcomas: impact and management of nodal metastasis.

PURPOSE: An epithelioid sarcoma is a rare histological subtype of a soft tissue sarcoma with a high local recurrence rate, which frequently shows lymph node metastasis. However, because of the rarity of this tumor, the impact of nodal metastasis and its appropriate management remain unclear. The present study investigated the clinical outcomes of patients with epithelioid sarcomas, with a focus on lymph node metastasis. METHODS: We retrospectively evaluated the clinical outcomes of 27 patients with epithelioid sarcomas treated between 1985 and 2015. The log-rank test was used to assess the prognostic variables. RESULTS: The overall local recurrence rate was 33%, and the estimated overall 5-year survival rate was 62%. Hand and foot locations were associated with favorable overall survival. During the follow-up period, new nodal metastasis was noted in 14 patients (52%). The incidence of local recurrence was higher in patients with new nodal metastasis than in patients who did not develop nodal metastasis. The development of new nodal metastasis had a tendency to worsen survival; however, this association was not statistically significant. Lymphadenectomy did not affect overall survival. CONCLUSIONS: Peripheral tumor location is associated with a better prognosis. The development of new nodal metastasis tends to be associated with poor prognosis; however, among patients with nodal metastasis, resection of the metastatic lesions has a low impact on survival.

Therapeutic potential of TAS-115 via c-MET and PDGFRα signal inhibition for synovial sarcoma.

BACKGROUND: The prognosis of synovial sarcoma (SS), an aggressive soft tissue sarcoma, remains poor. We previously reported that c-MET or platelet-derived growth factor receptor α (PDGFRα) signalling pathway is related to SS progression based upon the findings of phospho-receptor tyrosine kinase (RTK) arrays. TAS-115 is a novel c-MET/ vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitor that has been shown to inhibit multiple RTKs. Here we aimed to investigate the therapeutic potential of TAS-115 against SS. METHODS: We first evaluated which signalling pathway was relevant to the viability of three human SS cell lines: Yamato-SS, SYO-1 and HS-SY-II. Next, we assessed the anticancer activity and mechanism of action of TAS-115 in these SS cell lines. Finally, we compared the ability of TAS-115 to inhibit c-MET and PDGFRα phosphorylation with that of pazopanib. RESULTS: We classified the SS cell lines as c-MET-dependent or PDGFRα-dependent based upon the differences in the signalling pathway relevant for growth and/or survival. We also found that c-MET and PDGFRα were the primary activators of both phosphatidylinositol 3-kinase/AKT and mitogen-activated protein kinase pathways in c-MET-dependent and PDGFRα-dependent SS cells, respectively. TAS-115 treatment blocked the phosphorylation of PDGFRα as well as that of c-MET and their downstream effectors, leading to marked growth inhibition in both types of SS cell lines in in vitro and in vivo studies. Furthermore, PDGFRα phosphorylation, on at least four representative autophosphorylation sites, was impeded by TAS-115 equivalently to pazopanib. CONCLUSIONS: These experimental results have demonstrated the significance of c-MET and PDGFRα signalling for growth and/or survival of SS tumours. TAS-115 monotherapy may benefit SS patients whose tumours are dependent upon either c-MET or PDGFRα signalling by functioning as a multiple tyrosine kinase inhibitor to suppress c-MET as well as PDGFRα pathways.