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Background/Aim: Although smoking history is predictive of poor pulmonary metastasis-free survival (PMFS) in patients with epithelial tumors, the impact of smoking history on PMFS in those with soft-tissue sarcoma (STS) is not known. Patients and Methods: Patients undergoing treatment for STS at our institutes between 2008 and 2017 were enrolled. Patients were excluded if they had metastatic lesion, or had a histopathological classification demonstrating small round-cell sarcoma. The impact of smoking history on PMFS and overall survival was examined with multivariate analysis using a Cox proportional hazards model. Results: A total of 250 patients were retrospectively reviewed. Patients with smoking history had worse PMFS on multivariate analysis (hazard ratio=2.00, 95% confidence interval=1.12-3.60). On the other hand, smoking history did not significantly affect overall survival (hazard ratio=1.26, 95% confidence interval=0.61-2.58). Conclusion: Patients with STS need to be followed-up by frequent clinical assessments if they have a smoking history.

Background Hemarthrosis after total knee arthroplasty (TKA) is a relatively rare complication. Although most cases are effectively treated with conservative therapy, some cases require angiographic embolization or surgical intervention. Angiosarcoma is a rare malignant tumor derived from the vascular endothelium with neovascular hyperplasia and mainly arises in the skin and superficial soft tissue, and less frequently in deep soft tissue and bone. Although malignant neoplasms such as angiosarcoma in the vicinity of orthopedic implants were reported, the causal relationship between development of the malignant tumor and the orthopedic implant is widely debated in the literature. Case presentation We report the case of a 68-year-old female with angiosarcoma that developed in the knee joint 2 years after revision TKA. The patient exhibited severe persistent bleeding, which reached 1000–1400 ml per day for 4 months. Histological analysis of the synovial tissue in the knee joint showed large cells with nuclear atypia. Immunohistochemical staining showed cells that were positive for CD31, CD34, and D2-40, and she was diagnosed with angiosarcoma. The patient underwent an amputation at the level of the thigh, and her general condition immediately improved after the operation. The patient did not exhibit bleeding from the site of amputation, and no local recurrence or distant metastases were detected 1 year after the amputation. Conclusions To the best of our knowledge, this represents the first report of angiosarcoma 2 years after revision TKA. Further careful follow up is needed, given the high-grade malignancy.

Background: Hepatic metastasis of soft tissue sarcoma is rare compared to lung metastasis, and the literature is scarce. We examined the risk of hepatic metastasis according to the site of occurrence and histological type. Methods: From a Hospital-based Cancer Registry, 658 patients registered between 2007 and 2017 with soft tissue sarcomas were evaluated. The exclusion criteria were gastrointestinal stromal tumors, tumors of unknown origin, and follow-up periods of less than 1 month. SPSS 25 was used for statistical analysis. Results: The risk of hepatic metastasis was significantly higher in the retroperitoneum (HR, 5.981; 95% CI, 2.793-12.808) and leiomyosarcoma (HR, 4.303; 95% CI, 1.782-10.390). Multivariate analysis showed that the risk of hepatic metastasis as first distant metastasis was high in leiomyosarcoma (HR, 4.546; 95% CI, 2.275-9.086) and retroperitoneal onset (HR, 4.588; 95% CI, 2.280-9.231). The 2-year survival rate after hepatic metastasis was 21.7%. Conclusions: The onset of hepatic metastasis indicates a poor prognosis. However, hepatic metastasis from retroperitoneal sarcoma and leiomyosarcoma may be the first distant metastasis in some cases. For retroperitoneal sarcoma and leiomyosarcoma, additional screening for hepatic metastasis such as contrast CT should be considered during staging and follow-up after treatment., Article, Cancer medicine 17(17) : 6159-6165(2020)

Malignant peripheral nerve sheath tumor (MPNST) often does not respond well to chemotherapy and develops against a background of NF1. The purpose of our study was to examine the efficacy of pazopanib against MPNST. Our study was designed as a physician-initiated phase II clinical trial in patients with advanced MPNST. Patients were registered from 11 large hospitals. The primary endpoint was set to clarify the clinical benefit rate (CBR) at 12 weeks according to response evaluation criteria in solid tumors (RECIST). Progression-free survival (PFS), overall survival (OS) and the CBR based on modified Choi evaluation at week 12 were set as secondary endpoints along with treatment-related safety. The study enrolled 12 patients. Median age was 49 years. Seven had Grade 2 and five Grade 3 according to the FNCLCC evaluation. Median follow-up period was 10.6 months. CBR at 12 weeks was both 50.0% (RECIST and Choi). The median PFS was 5.4 months for both RECIST and Choi, and the median OS was 10.6 months. Of special interest, the median PFS was 2.9 months for patients with FNCLCC Grade 2 and 10.2 months for Grade 3 (both RECIST and Choi). Grade 4 adverse events of neutropenia and lipase elevation were noted in one patient each. The results of this pazopanib therapy were generally better than those of any of the other single molecular targeted therapies reported previously. Although accumulation of more cases remains necessary, we conclude pazopanib treatment for MPNST to be a safe and promising treatment after doxorubicin-based chemotherapy.

The currently approved dose of pazopanib (800mg) is being re-examined owing to its adverse effects. The aim of this study was to evaluate the relationships among starting or maintenance doses of pazopanib, estimated pazopanib C-min, and other clinical factors, including albumin and a-1 acid glycoprotein levels, in soft-tissue sarcoma and renal cell carcinoma. We also determined whether therapeutic drug monitoring of pazopanib concentrations may be used to improve its therapeutic efficacy and prevent adverse effects. Forty patients who received pazopanib for renal cancer or soft-tissue sarcoma at the Hokkaido Cancer Center were evaluated prospectively. C-min, for pazopanib was calculated based on the measured values from the plasma samples. The efficacy and time to treatment failure were then assessed. The pazopanib maintenance doses were 200 (n=4), 400 (n=34), 600 (n=4), and 800mg (m = 1). Most patients (65%) who received a 400 mg dose had an effective pazopanib concentration (>= 20//g/mL), whereas 35% of patients who received the 400mg dose had ineffective concentrations (

The time course of the response to each drug is important to avoid inappropriate termination of treatment by misjudging tumor progression; however, little is known about soft tissue sarcoma (STS) regarding this matter. This study aimed to perform a time‐lapse analysis of tumor response in patients with STS treated with trabectedin from 2 phase II clinical trials. We examined 66 patients with translocation‐related sarcoma registered in 2 Japanese phase II clinical trials. All patients previously received standard therapy before the administration of trabectedin at 1.2 mg/m2 every 3 weeks. Imaging evaluation was performed according to the study protocol. The sum of the maximum diameters of the target lesions was calculated and analyzed over time. Among the 66 patients, 9 (13.6%) showed partial response (PR) to trabectedin. Histological diagnoses of these 9 responders comprised 6 myxoid liposarcoma, 2 synovial sarcoma, and a mesenchymal chondrosarcoma. The median period from treatment initiation to the first PR was 123 (range, 34‐328) days. The pattern of tumor response to trabectedin showed an increasing tendency in size in the initial stage, usually followed by a size decrease with repeated administration. STS response to trabectedin was characterized as delayed and potentially persistent. Clinicians treating STS with trabectedin should know the features of the response pattern to avoid interrupting the treatment before maximal efficacy is achieved., Among 66 patients with translocation‐related sarcoma, 9 showed partial response to trabectedin, and 5 of the 9 responders (56%) fulfilled the criteria for partial response later than 100 days from treatment initiation. Tumor response to trabectedin was characterized as delayed and stabilized by the detailed time‐lapse analysis of tumor size.

Background Primary osteosarcoma in elderly patients are rare malignant tumors. Its optimal treatment has not yet been determined. Methods This retrospective study included 104 patients aged >50 years with resectable, non-metastatic osteosarcoma treated by the members of the Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group. The effects of adjuvant chemotherapy were estimated by comparing outcomes in patients who received surgery plus chemotherapy with those who underwent surgery alone. Results Median age at presentation was 59 years. Neoadjuvant and adjuvant chemotherapy was administered to 83 (79.8%) patients. Patients who underwent surgery plus chemotherapy and those who underwent surgery alone had 5-year overall survival (OS) rates of 68.6% and 71.7%, respectively (p = 0.780), and 5-year relapse free survival (RFS) rates of 48.2% and 43.6%, respectively (p = 0.64). Univariate analysis showed that resection with wide margins was significantly correlated with better prognosis. Conclusions The addition of chemotherapy to surgery did not improve OS or RFS in patients aged >50 years with resectable, non-metastatic osteosarcoma. Surgery with wide margins was only significantly prognostic of improved survival. The effect of chemotherapy in elderly osteosarcoma patients was unclear.

Previous studies have not clearly identified a prognostic factor for desmoid tumours (DT). Whole-exome sequencing (WES) and/or RNA sequencing (RNA-seq) were performed in 64 cases of DT to investigate the molecular profiles in combination with the clinicopathological characteristics. CTNNB1 mutations with specific hotspots were identified in 56 cases (87.5%). A copy number loss in chromosome 6 (chr6) was identified in 14 cases (21.9%). Clustering based on the mRNA expression profiles was predictive of the patients' prognoses. The risk score generated by the expression of a three-gene set (IFI6, LGMN, and CKLF) was a strong prognostic marker for recurrence-free survival (RFS) in our cohort. In risk groups stratified by the expression of IFI6, the hazard ratio for recurrence-free survival in the high-risk group relative to the low-risk group was 12.12 (95% confidence interval: 1.56–94.2; p = 8.0 × 106). In conclusion, CTNNB1 mutations and a chr6 copy number loss are likely the causative mutations underlying the tumorigenesis of DT while the gene expression profiles may help to differentiate patients who would be good candidates for wait-and-see management and those who might benefit from additional systemic or radiation therapies.

Alveolar soft part sarcoma (ASPS), epithelioid sarcoma (ES), and clear cell sarcoma (CCS) are known to be chemoresistant tumors. The aim of this study was to investigate the effect of pazopanib on these chemoresistant tumors. This study is designed as a single‐arm, multicenter, investigator‐initiated phase II trial. Patient enrollment was undertaken between July 2016 and August 2018 at 10 hospitals participating in the Japanese Musculoskeletal Oncology Group. The primary end‐point is the CBR (CBR, including complete or partial response and stable disease) at 12 weeks after treatment with pazopanib according to RECIST. Eight patients were enrolled within the period. The histological subtypes were 5 ASPS, 2 ES, and 1 CCS. The median follow‐up period was 22.2 (range, 4.9‐24.9) months. All patients initially received pazopanib 800 mg once daily. The CBRs were 87.5% (7 of 8) and 75.0% (6 of 8) according to RECIST and Choi criteria at 12 weeks after pazopanib treatment, respectively. The CBRs at 12 weeks according to RECIST were 80.0%, 100.0%, and 100.0% in ASPS, ES, and CCS, respectively. Partial response was observed in 1 ASPS according to RECIST and 3 ASPS and 1 ES according to Choi criteria at 12 weeks after pazopanib treatment. This study documented antitumor activity of pazopanib, especially in ASPS. These results support the frontline use of pazopanib for ASPS. Prospective data collection is desired using both RECIST and Choi criteria for these rare chemoresistant tumors., This prospective study, carried out among the Japanese reference centers for treatment of sarcomas, confirmed the value of pazopanib in patients with metastatic or unresectable chemoresistant sarcomas (alveolar soft part sarcoma, epithelioid sarcoma, and clear cell sarcoma). Pazopanib showed antitumor activity in most patients with alveolar soft part sarcoma according to RECIST and Choi criteria. These results support the frontline use of pazopanib for alveolar soft part sarcoma.

Background Soft tissue sarcomas (STS) are rare malignant tumors. The efficacy of preoperative chemotherapy for STS is evaluated using various tumor size-based radiological response criteria. However, it is still unclear which set of criteria would show the best association with pathological response and survival of the patients with STS. Methods We compared radiological responses to preoperative chemotherapy for operable STS by the Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST, World Health Organization criteria, Japanese Orthopaedic Association criteria, and modified Choi criteria and analyzed the association with pathological response and survival using the data from the Japan Clinical Oncology Group (JCOG) study JCOG0304, a phase II clinical trial evaluating the efficacy of perioperative chemotherapy for STS in the extremities. Results Seventy eligible patients in JCOG0304 were analyzed. The results demonstrated that none of the size-based radiological response criteria showed significant association with pathological response to preoperative chemotherapy for STS. The difference between overall survival of the patients assessed as partial response and stable disease/progressive disease by RECIST was not significant (hazard ratio 1.37, p = 0.63), and calculated C-index was 0.50. All other response criteria also could not exhibit significant association between radiological responses and survival. Conclusion In the present study, none of the radiological response criteria analyzed demonstrated association of response to preoperative chemotherapy with pathological response or survival of the patients with operable STS. Further prospective investigation is required to develop criteria to evaluate not only tumor shrinkage but biological effects of preoperative chemotherapy for the patients with localized STS. Trial registration UMIN Clinical Trials Registry C000000096. Registered 30 August, 2005 (retrospectively registered).

TPS11580 Background: Soft tissue sarcomas (STS) are a rare type of malignancy, which comprises of a variety of histologies. Chemotherapy is the standard treatment for patients with advanced STS. Doxorubicin alone or in combination with ifosfamide is widely accepted as the first-line chemotherapy for advanced STS. While a combination with gemcitabine and docetaxel is regarded as a standard regimen of the second-line chemotherapy after failure of doxorubicin-based first-line regimen, the efficacy is not sufficient. Trabectedin, eribulin, and pazopanib are the candidates of the second-line chemotherapy for advanced STS, although there is no clear evidence showing which is better among those agents. The purpose of this clinical trial conducted by Bone and Soft Tissue Tumor Study Group of Japan Clinical Oncology Group (JCOG) is to determine the most promising regimen among trabectedin, eribulin and pazopanib as the test arm regimen in the future phase III trial of the second-line treatment for patients with advanced STS. Methods: The study, JCOG1802, is a multicenter, selection design, randomized phase II trial comparing trabectedin (1.2 mg/m2 IV, every 3 weeks), eribulin (1.4 mg/m2 IV, days 1 and 8, every 3 weeks) and pazopanib (800 mg PO, everyday) for patients with unresectable or metastatic STS refractory to doxorubicin-based first-line chemotherapy. Eligibility criteria include 16 year-old or older, unresectable and/or metastatic STS, an exacerbation within 6 months prior to registration, histological diagnosis of STS other than Ewing sarcoma, well-differentiated liposarcoma and myxoid liposarcoma, a history of chemotherapy for STS other than doxorubicin-based regimen, ECOG (Eastern Cooperative Oncology Group) performance status 0 to 2, and sufficient organ function. Primary endpoint is progression-free survival (PFS), and secondary endpoints include overall survival, disease-control rate, response rate, and adverse events. To select the most promising regimen in median PFS (3 months in the worst regimen and 4 months in the best regimen) with a probability of at least 80%, a total of 120 patients will be enrolled from 37 institutions in Japan. After JCOG1802, a subsequent phase III trial comparing the winner of this study and a combination of gemcitabine and docetaxel will be planned. The study was activated at December 5, 2019 and 22 of planned 120 patients have been enrolled as of February 15, 2021. Clinical trial information: jRCTs031190152.

Background Leiomyosarcoma of bone (LMSoB) is a rare malignant bone tumor. This multicenter retrospective study was conducted to investigate the diagnosis and the clinical outcome of primary LMSoB in Japan. Methods Forty-eight patients (average age: 52 years [range 14–88 years]) with primary LMSoB who were treated at registered institutes in Japan between 1991 and 2014 were recruited. The median follow-up period was 44 months (range: 2–273). Results The 5-year overall survival rates and disease-free survival rates were 78.3% and 44.9%, respectively. Surgical treatment was performed in 42 patients, and R0 resection was achieved in 31 patients. Neoadjuvant chemotherapy was administered in 18 patients. The most common regimen (cisplatin-based chemotherapy) was administered in 15 patients, however, no patient achieved a good response in both radiological and histological evaluations. The presence of metastasis at the first visit and a lack of definitive surgery were significantly correlated with poor overall survival, and the surgical margin was a significant prognostic factor for disease-free survival. Conclusions This study is the largest LMSoB case series ever reported. Surgical treatment with wide margins was the only treatment that proved to be effective, whereas adjuvant chemotherapy in the present setting did not improve the overall survival. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

Purpose To evaluate the results of carbon ion radiation therapy administered to 188 patients with unresectable primary sacral chordomas. Patients and methods One hundred eighty-eight patients were treated with carbon ion radiation therapy at a single institute between 1996 and 2013 and retrospectively analyzed. The median age was 66 years. The highest proximal invasion reached past S2 level in 137 patients. The median clinical target volume was 345 cm(3). One hundred six patients received 67.2 gray equivalents (GyE)/16 fractions (fr), 74 patients received 70.4 GyE/16 fr, 7 patients received 73.6 GyE/16 fr, and 1 patient received 64.0 GyE/16 fr. Results The median follow-up period was 62 months (range, 6.8-147.5 months). Seventy percent of patients were followed for 5 years or until death. The 5-year local control, overall survival, and disease-free survival rates were 77.2%, 81.1%, and 50.3%, respectively. Forty-one patients had a local recurrence. Sex, tumor volume, level of proximal invasion, and irradiated dose were unrelated to local control. There was grade 3 toxicity of the peripheral nerves in 6 patients and grade 4 toxicity of the skin in 2 patients. Ambulation remained in 97% of patients. Conclusions Carbon ion radiation therapy was safe and effective for unresectable chordoma and provided good local control and survival while preserving ambulation.

Aim Our randomised phase II study showed the clinical benefit of trabectedin compared with best supportive care (BSC) in patients with advanced translocation-related sarcomas after the failure of standard chemotherapy. The aim of the present study was to evaluate efficacy and safety of trabectedin in the identical patients crossed over to trabectedin after disease progression in the BSC arm of the randomised study. Patients and methods This was a single-arm study of the BSC patients of the randomised study in whom disease progressed. Trabectedin (1.2 mg/m 2 ) was administered over 24 h on day 1 of a 21-d treatment cycle. The efficacy and safety of trabectedin after BSC were evaluated and retrospectively compared with the results of the randomised study. Results Thirty patients crossed over to trabectedin. Median progression-free survival (PFS) was 7.3 months (95% confidence interval [CI]: 2.9–9.1) after crossover compared with 0.9 months (95% CI: 0.9–1.0) at BSC in the randomised study. PFS in the present study was comparable to that of the trabectedin arm in the randomised study. The number of patients with growth modulation index ≥1.33 was 25 (86%). Individual tumour volume was decreased in 11 patients after crossover. Adverse drug reactions (ADRs) were observed in 27 patients (96.4%). ADRs of grade III–IV were mainly bone marrow suppression and abnormal liver functions. Conclusion Trabectedin was revealed to be effective and well tolerated in the identical patients crossed over to trabectedin after disease progression in BSC. The present study is registered with the Japan Pharmaceutical Information Center, number JapicCTI-121853.

11504 Background: Our previous phase II study for high-grade soft tissue sarcomas (STS), JCOG0304, suggested long-term favorable effects of perioperative adriamycin plus ifosfamide (AI) on survival of STS patients. We have also reported in 2015 ASCO Annual Meeting that a phase II/III trial to confirm the non-inferiority of perioperative gemcitabine plus docetaxel (GD) to AI for high-grade STS (JCOG1306) had been started. We herein report the results of JCOG1306 at the early termination by the preplanned second interim analysis. Methods: Patients with operable, FNCLCC grade 2/3 STS primary tumor (T2bN0M0 or anyTN1M0, AJCC 7th edition) or first local recurrent tumor in the extremities or trunk were randomized to AI or GD. Chemotherapy consisted of adriamycin 60 mg/m2 plus ifosfamide 10 g/m2 for AI or gemcitabine 1,800 mg/m2 plus docetaxel 70 mg/m2 for GD. The treatments were repeated for 3 courses preoperatively and 2 courses postoperatively in a 3-week interval. The primary endpoint in phase III part was overall survival (OS). Planned sample size was 140 with a one-sided alpha of 0.1, power of 0.7 and a non-inferiority margin of 8% at 3-year OS, assuming 3-year OS of AI to be 85% and that of GD as 87%. The patient accrual has started in February 2014 and finished in September 2018. Results: A total of 143 patients were enrolled and included in the efficacy analysis. Seventy and 73 patients were assigned to AI and GD, respectively. At the second interim-analysis on December 2019, the estimated 2-year OS was 94.3 % (95% confidence interval (CI) 83.4–98.1) in AI and 91.6 % (80.9–96.4) in GD (hazard ratio (HR) 2.55, 95% CI 0.67–9.78). The estimated 2-year progression-free survival was 81.9 % (95% CI: 69.5–89.7) in AI and 64.0 % (51.1–74.4) in GD (HR 2.32, 95% CI 1.22–4.39). There were no treatment-related deaths in both groups. The most common Grade 3 or higher adverse events in AI were neutropenia (88.4%), anemia (49.3%), and febrile neutropenia (36.2%), whereas those in GD were neutropenia (79.5%), febrile neutropenia (17.8%), and alanine aminotransferase (9.6%). Based on the result of this analysis, the Data Monitoring and Safety Committee of JCOG recommended terminating the study since the point estimate of HR was above the pre-specified allowable HR of 1.61. Conclusions: Although the toxicities were modest in GD, non-inferiority of GD to AI could not be confirmed. In the perioperative chemotherapy for high-grade STS in the extremities and trunk, AI remains the standard regimen. Clinical trial information: UMIN000013175 .

A randomized phase III trial was planned to commence in October 2017. Resectable giant cell tumor of bone (GCTB) without possible postoperative large bone defect has been treated by curettage with local adjuvant treatment, with the local recurrence rate found to be as high as 24.6-30.8%. The aim of this study is to confirm the superiority of preoperative denosumab for patients with GCTB without possible postoperative large bone defect. A total of 106 patients will be accrued from 34 Japanese institutions over 5 years. The primary endpoint is relapse-free survival (RFS). Secondary endpoints include overall survival, joint-preserved survival, local RFS, metastasis-free survival, adverse events, serious adverse events, surgical and postoperative complications, and discontinuation of denosumab. This trial is conducted by the Bone and Soft Tissue Tumor Study Group in the Japan Clinical Oncology Group and has been registered in the UMIN Clinical Trials Registry as UMIN000029451 [http://www.umin.ac.jp/ctr/index.htm].

A randomized Phase II/III trial was planned to commence in March 2014. Perioperative chemotherapy with adriamycin plus ifosfamide is the current standard treatment for T2bN0M0 high-grade non-round cell soft tissue sarcoma. The purpose of this study is to confirm the non-inferiority of perioperative chemotherapy with gemcitabine and docetaxel to adriamycin plus ifosfamide for patients with T2bN0M0 or any TN1M0 non-round cell soft tissue sarcoma in the extremities and body wall. A total of 140 patients will be accrued from 28 Japanese institutions over 6 years. The primary endpoint in the Phase II part is the proportion of completion of pre-operative chemotherapy without progressive disease and overall survival in the Phase III part. The secondary endpoints are progression-free survival, response rate of pre-operative chemotherapy, pathological response rate, proportion of preservation of diseased limbs, disease control rate and proportion of adverse events. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000013175 [http://www.umin.ac.jp/ctr/index.htm].

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.

The tensor fascia lata (TFL) flap is used to reconstruct various anatomical structures in different regions of the body. We herein describe the use of TFL flaps for a variety of indications, and discuss the results of such procedures with respect to postoperative complications in oncology patients. We reviewed 15 oncology patients who were treated with TFL flaps. The lesions were located in the groin in five patients, the lower abdomen in five, and the buttocks, ischium, shoulder, thigh and upper abdomen in one patient each. Abdominal wall reconstruction was performed in nine patients. Three patients underwent resection of femoral vessels and the tumor in the groin, followed by a vascular graft implant. In these patients, the combined flaps were transferred to reconstruct the defects. Nine patients developed complications. No total flap loss occurred in any patient. Postoperative complications, such as necrosis in the distal part of the flap (33 %) and ventral hernias (11 %) were seen, but these percentages were comparable to those seen in previous reports. Our review shows that the TFL flap is useful to reconstruct the defects in various anatomical sites in oncology patients.

The posterior thigh flap is a reliable flap owing to the dependability of the inferior gluteal artery. Its utility for the reconstruction of sacral, perineal, ischial, pelvic, trochanteric and vulvar defects is well established. We herein describe the use of the flap for a variety of indications, and discuss the results with respect to postoperative complications in oncology patients. We reviewed nine oncology patients who were treated with pedicled posterior thigh flaps. We assessed the use of this treatment by recording the site of the defect, the type of flap used, and the presence or absence of previous surgical procedures, radiation therapy and postoperative complications. Defects after resection of soft tissue sarcomas were the most common condition (n = 4), followed by skin cancers (n = 2), gastrointestinal cancers (n = 2) and radiation osteomyelitis (n = 1). Six patients (66 %) developed complications; three (33 %) were major and three (33 %) were minor. There was one case of total necrosis of the flap and two cases of partial necrosis. In oncology patients, the posterior thigh flap is an excellent choice for the reconstruction of sacral, ischial, pelvic or buttock defects, since it does not cause any donor site morbidity.

Trabectedin is reported to be particularly effective against translocation-related sarcoma. Recently, a randomized phase 2 study in patients with translocation-related sarcomas unresponsive or intolerable to standard chemotherapy was conducted, which showed clinical benefit of trabectedin compared with best supportive care (BSC). Extraskeletal myxoid chondrosarcoma (EMCS) and Mesenchymal chondrosarcoma (MCS) are very rare malignant soft tissue sarcomas, and are associated with translocations resulting in fusion genes. In addition, the previous in vivo data showed that trabectedin affect tumor necrosis and reduction in vascularization in a xenograft model of a human high-grade chondrosarcoma. The aim of the present analysis was to clarify the efficacy of trabectedin for EMCS and MCS subjects in the randomized phase 2 study. Five subjects with EMCS and MCS received trabectedin treatment in the randomized phase 2 study. Three MCS subjects were allocated to the BSC group. Objective response and progression-free survival (PFS) were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by central radiology imaging review. The median follow-up time of the randomized phase 2 study was 22.7 months, and one subject with MCS was still receiving trabectedin treatment at the final data cutoff. The median PFS was 12.5 months (95 % CI: 7.4–not reached) in the trabectedin group, while 1.0 months (95 % CI: 0.3–1.0 months) in MCS subjects of the BSC group. The six-month progression-free rate was 100 % in the trabectedin group. One subject with MCS showed partial response, and the others in the trabectedin group showed stable disease. Overall survival of EMCS and MCS subjects was 26.4 months (range, 10.4–26.4 months) in the trabectedin group. At the final data cutoff, two of five subjects were still alive. This sub-analysis shows that trabectedin is effective for patients with EMCS and MCS compared with BSC. The efficacy results were better than previously reported data of TRS. These facts suggest that trabectedin become an important choice of treatment for patients with advanced EMCS or MCS who failed or were intolerable to standard chemotherapy. The randomized phase 2 study is registered with the Japan Pharmaceutical Information Center, number JapicCTI-121850 (May 31, 2012).

This analysis updates the results of two phase II studies of translocation‐related sarcomas to evaluate the efficacy of trabectedin against histological subtype and analyze overall survival., Background. Trabectedin is reported as effective, especially against translocation‐related sarcomas (TRSs) after failure of or intolerance to standard chemotherapy. We conducted two phase II studies of TRS, confirming high efficacy of 1.2 mg/m2 trabectedin. The updated data of 66 patients in these studies was integrated to evaluate the efficacy of trabectedin against each histological subtype, and analyze final overall survival (OS). Methods. Trabectedin was administered on day one of a 21‐day cycle. Efficacy was assessed using progression‐free survival (PFS), OS, and best overall response. An analysis of OS and PFS was performed for subgroups divided by baseline lymphocyte count (

The survival of patients with osteosarcoma has improved dramatically due to the introduction of effective systemic chemotherapy. The key standard drugs for osteosarcoma chemotherapy are methotrexate, doxorubicin, and cisplatin, and multi-institutional trials based on these drugs have been conducted in Japan since the 1990s. However, there have been no nationwide data on treatment outcome, especially with regard to survival and prognostic factors. In this chapter, therefore, we present data from a large nationwide cohort of patients with osteosarcoma treated at 11 referral centers in Japan during the period 1990–2010 with special reference to survival and relevant prognostic factors. The 3-, 5-, and 10-year metastasis-free survival and overall survival rates for the 529 patients were 70 %, 64 %, and 62 % and 88 %, 83 %, and 77 %, respectively. The prognosis for patients with osteosarcoma in Japan was comparable to, or slightly better than, those reported in other countries. International collaboration should also be conducted in Asian countries including Japan to improve the outcome further and find the optimal treatment for osteosarcoma.

Adjuvant chemotherapy is a standard treatment for osteosarcoma, which was verified by two randomized controlled trials (RCTs). Preoperative chemotherapy and limb-preserving procedure have been developed in the USA since around 1970 and in Japan since around 1980. In addition, histologic evaluation concerned with the rate of necrosis of excised tumors after preoperative chemotherapy has been tried, and it has been reported that patients with higher rate of necrosis result in better survival. Neoadjuvant chemotherapy for osteosarcoma (NECO) study tried to improve survival of the patients with lower rate of necrosis, called as “poor responders,” by the changes or addition of chemotherapeutic agents on the basis of the histologic evaluation in Japan, and the study found the possibility to rescue poor responders. Such strategies, however, have not been verified by RCT yet. Now additional effects of ifosfamide (IFO) to postoperative chemotherapy for poor responders after preoperative chemotherapy and surgery are just tested by two RCTs.

BACKGROUND Because the efficacy and safety of pazopanib in Japanese patients with soft tissue sarcoma (STS) had not been evaluated previously in a large‐scale cohort, the authors investigated the efficacy and safety of pazopanib in 156 Japanese patients with relapsed STS. This was a retrospective study based on the collection of real‐life, postmarketing surveillance data. METHODS Patients received pazopanib with the objective of treating local recurrence (n = 20), metastasis (n = 104), and both (n = 32). The patient median age was 53.8 years. The primary objective of this study was to clarify the efficacy of pazopanib for patients with STS. RESULTS The median treatment duration was 28.7 weeks, and the average dose intensity of pazopanib was 609 mg. Adverse events occurred in 127 patients (81.4%). In addition to the main common toxicities, such as hypertension and liver disorder, pneumothorax (n = 11) and thrombocytopenia (n = 16) also were observed. The median progression‐free survival for all patients was 15.4 weeks. The median progression‐free survival for patients with leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma was 18.6 weeks, 16.4 weeks, 15.3 weeks, and 8 weeks, respectively. The median survival for all patients was 11.2 months. The median survival for patients with leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma was 20.1 months, 10.6 months, 9.5 months, and 7.3 months, respectively. CONCLUSIONS There were apparent differences in the efficacy of pazopanib treatment among histologic types of STS. Pazopanib treatment is a new treatment option; however, adverse events like pneumothorax and thrombocytopenia, which did not occur frequently in the PALETTE study (pazopanib for metastatic soft‐tissue sarcoma), should be taken into consideration. Cancer 2016;122:1408‐16. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society., Clinical outcomes of 156 Japanese patients with relapsed soft tissue sarcoma receive pazopanib treatment are investigated. There are apparent differences in the efficacy of pazopanib treatment among histologic types of soft tissue sarcoma.

Background Giant cell tumor of bone (GCTB) is an intermediate tumor known to be locally aggressive, but rarely metastasizing. To plan a prospective study of GCTB, we performed a questionnaire survey for institutions participating in the Bone and Soft Tissue Tumor Study Group (BSTTSG) in the Japan Clinical Oncology Group (JCOG) in 2015. Methods We reviewed 158 consecutive patients with primary GCTB treated with curettage without perioperative denosumab from 2008 to 2010 in Japan. We investigated local and distant recurrence rates after definitive curettage. We also investigated the recurrence rate after treatment with preoperative and/or postoperative denosumab with curettage in recent years. There were 40 patients treated with perioperative denosumab, and the factors affecting recurrence in them were investigated. Results Answers were available from 24 of 30 institutions (80.0%) participating in JCOG BSTTSG. Thirty (19.0%) and 4 (2.5%) of 158 patients developed local and distant recurrence after curettage without perioperative denosumab from 2008 to 2010, respectively. Campanacci grade and embolization before surgery were significantly associated with increasing incidence of local recurrence after curettage (p = 0.034 and p = 0.022, respectively). In patients treated with perioperative desnosumab, 120 mg denosumab was administered subcutaneously for a median 6 (2–41) and 6 (1–14) times in preoperative and postoperative settings, respectively. The recurrence rates were 6 of 21 (28.6%), 2 of 9 (22.2%), and 0 of 10 (0.0%) in the preoperative, postoperative, and both pre- and postoperative denosumab treatment groups, respectively. With all of the preoperative treatments, administration exceeding five times was significantly associated with a decreased incidence of local recurrence after curettage (p

Objective This analysis of the Japanese subpopulation of the PALETTE Phase III, randomized, placebo-controlled study investigated efficacy and safety of pazopanib in patients with metastatic soft tissue sarcoma after failure of standard chemotherapy. Methods Patients were randomly assigned in a 2:1 ratio to receive either pazopanib 800 mg once daily or placebo, with no subsequent cross-over. Primary endpoint was progression-free survival. Secondary endpoints included overall survival and overall response rate. Efficacy analysis was by intent-to-treat. Safety was also investigated. Results Forty-seven patients received either pazopanib (n = 31) or placebo (n = 16). Median progression-free survival was 7.0 weeks (95% confidence interval: 4.0–11.7) for placebo and 24.7 weeks (95% confidence interval: 8.6–28.1) for pazopanib (hazard ratio = 0.41 [95% confidence interval: 0.19–0.90]; P = 0.002). Median overall survival was 14.9 months (95% confidence interval: 6.8—not calculable) for placebo and 15.4 months (95% confidence interval: 7.9–28.8) for pazopanib (hazard ratio = 0.87 [95% confidence interval: 0.41–1.83]; P = 0.687). More patients receiving pazopanib experienced best response of stable disease versus placebo. Adverse events were similar to the global population; those leading to dose reduction were more common and mean daily dose was lower in the Japanese population versus the global population (45 vs. 32% and 624.4 vs. 700.4 mg, respectively). Conclusions The efficacy and safety of pazopanib observed in the Japanese subpopulation of PALETTE were similar to those in the global population. Pazopanib is a new treatment option for Japanese patients with metastatic non-adipocytic soft tissue sarcoma after chemotherapy. Clinical trial Registration number NCT00753688; GSK study ID: VEG110727; http://www.gsk-clinicalstudyregister.com/study/VEG110727#ps.

Trabectedin binds to the minor groove of DNA and blocks DNA repair machinery. Preclinical data have shown that trabectedin also modulates the transcription of the oncogenic fusion proteins of translocation-related sarcomas. We aimed to assess the efficacy and safety of trabectedin as second-line therapy or later for patients with advanced translocation-related sarcoma.We did a multicentre randomised open-label study in Japan. Eligible patients had pathological diagnosis of translocation-related sarcoma, were aged 19 years or older, were unresponsive or intolerant to standard chemotherapy regimens, no more than four previous chemotherapy regimens, Eastern Cooperative Oncology Group performance status 0 or 1, adequate bone marrow reserve, renal and liver functions, and had measurable lesions. Patients were randomly assigned (1:1) by the minimisation method to receive either trabectedin (1·2 mg/m(2) given via a central venous line over 24 h on day 1 of a 21 day treatment cycle) or best supportive care, which was adjusted centrally by pathological subtype. Investigators, patients, and the sponsor were unmasked to the treatment assignment. Progression-free survival and objective responses were assessed by a masked central radiology imaging review. Efficacy was assessed by masked central radiology imaging review. The primary endpoint was progression-free survival for the full analysis set population. Follow-up is ongoing for the patients under study treatment. The study is registered with Japan Pharmaceutical Information Center, number JapicCTI-121850.Between July 11, 2012, and Jan 20, 2014, 76 patients were enrolled and allocated to receive either trabectedin (n=39) or best supportive care (n=37). After central review to confirm pathological subtypes, 73 patients (37 in the trabectedin group and 36 in the best supportive care group) were included in the primary efficacy analysis. Median progression-free survival of the trabectedin group was 5·6 months (95% CI 4·1-7·5) and the best supportive care group was 0·9 months (0·7-1·0). The hazard ratio (HR) for progression-free survival of trabectedin versus best supportive care was 0·07 (90% CI 0·03-0·14 and 95% CI 0·03-0·16) by a Cox proportional hazards model (p0·0001). The most common drug-related adverse events for patients treated with trabectedin were nausea (32 [89%] of 36), decreased appetite (21 [58%]), decreased neutrophil count (30 [83%]), increased alanine aminotransferase (24 [67%]), and decreased white blood cell count (20 [56%]).Trabectedin significantly reduced the risk of disease progression and death in patients with advanced translocation-related sarcoma after standard chemotherapy such as doxorubicin, and should be considered as a new therapeutic treatment option for this patient population.Taiho Pharmaceutical Co., Ltd.

To investigate the clinical significance of circulating angiogenic factors, especially in association with early relapse of osteosarcoma, we quantified pre-therapeutic levels of vascular endothelial growth factor, basic fibroblast growth factor and placenta growth factor in the sera of 16 patients with osteosarcoma using an enzyme-linked immunosorbent assay. After a 1-year follow-up, the serum level of angiogenic factors was analysed with respect to microvessel density of the biopsy specimen and clinical disease relapse. The serum vascular endothelial growth factor levels were positively correlated with the microvessel density with statistical significance (P=0.004; Spearman rank correlation) and also significantly higher in seven patients who developed pulmonary metastasis than the remaining nine patients without detectable disease relapse (P=0.0009; The Mann–Whitney U-test). In contrast, the serum levels of basic fibroblast growth factor or placenta growth factor failed to show significant correlation with the microvessel density or relapse of the disease. Although there was no significant correlation between serum vascular endothelial growth factor levels and the tumour volume, the serum vascular endothelial growth factor levels were significantly higher in patients with a vascular endothelial growth factor-positive tumour than those with a vascular endothelial growth factor-negative tumour. These findings suggest that the pre-therapeutic serum vascular endothelial growth factor level reflects the angiogenic property of primary tumour and may have a predictive value on early disease relapse of osteosarcoma. British Journal of Cancer (2002) 86, 864–869. DOI: 10.1038/sj/bjc/6600201 www.bjcancer.com © 2002 Cancer Research UK

Diffuse-type tenosynovial giant cell tumor (TS-GCT) is categorized as a locally aggressive but non-metastasizing neoplasm according to the WHO classification. Herein, we report an extremely rare case of a 41-year-old woman who developed multiple metastases from diffuse TS-GCT with benign histological features. The patient complained of a painful buttock mass and imaging studies revealed a soft tissue tumor of the buttock and multiple pulmonary nodules. The buttock tumor was excised and the final diagnosis was extra-articular diffuse-type TS-GCT. By video-assisted thoracic surgery, pulmonary nodules were pathologically identical to the primary tumor. Residual pulmonary nodules progressively grew, and she developed a muscle metastasis and a subcutis metastasis. She died of respiratory dysfunction due to multiple pulmonary metastases 1 year after primary surgery. Very few reports on histologically benign metastases from TS-GCT have been published, and the natural course of this rare condition remains unclarified. This rare case could provide important information for further clinical evaluation of this tumor.

Adult onset Leigh syndrome with a nucleotide (nt) 8993 mutation in mitochondrial (mt) DNA is reported. A 43-year-old woman with a 6-year-history of insulin-resistant diabetes mellitus developed muscular weakness, intractable nausea and vomiting, and anemia. These were followed vertigo, blindness, and deafness with nystagmus. Magnetic resonance imaging (MRI) revealed abnormal high intensities in the bilateral medial regions of the thalamus and periaqueductal gray matters. Autopsy disclosed well-demarcated necrotizing lesions with prominent capillaries in the areas detected by MRI, which were sufficiently diagnostic for Leigh syndrome. MtDNA analysis performed on DNAs extracted from formalin-fixed tissues including liver, heart, brain, muscle, kidney and pancreas showed a T-->G mutation at nt 8993. This is the first case of adult Leigh syndrome demonstrating on mtDNA mutations.

The chimeric transcript SYT-SSX is generated as a result of reciprocal translocation t(X;18), which is the primary cytogenetic abnormality found in, and appears to be specific for, synovial sarcoma. We performed a reverse transcriptase-polymerase chain reaction (RT-PCR) for SYT-SSX transcripts in a series of 84 tumors (61 soft tissue tumors and 23 bone tumors), including a variety of histologic types, to assess its usefulness in molecular diagnosis. Ten synovial sarcomas, three tumors initially unclassified, and one malignant peripheral nerve sheath tumor contained the chimeric transcripts. A review of the original slides and additional examination showed that a diagnosis of synovial sarcoma was appropriate for these cases. Additionally, in situ hybridization with an SSX1 probe indicated that the chimeric transcripts exist not only in the cells of special components but also in cells showing a variety of histologic patterns. Therefore, RT-PCR can be considered a useful molecular biological technique that can provide objective evidence for diagnosis of synovial sarcoma. Northern blot analysis with an SSX1 probe also detected chimeric SYT-SSX transcripts in the synovial sarcoma cases. The additional smaller bands, however, were also detected in six peripheral primitive neuroectodermal tumors (pPNETs) and one embryonal rhabdomyosarcoma. In five of these pPNETs, other bands ranging in size from 2.0 to 2.2 kb were also found, and it seems possible that these bands might represent novel karyotypic aberrations and/or splicing variants of SSX.

Clear cell sarcoma (CCS), a rare tumour of deep soft tissues, often has a t(12; 22) (q13; q12) translocation that induces the formation of a hybrid EWS/ATF-1 gene. To investigate these alterations further, we established a new continuous cell line directly from a CCS taken from a 9-year-old girl. The cultures were characterized with respect to morphological, ultrastructural, immunohistochemical and karyotypical features and were tested by reverse transcription PCR (RT-PCR) for chimaeric EWS/ATF-1 transcripts. The continuous cell line, designated KAO, is tumorigenic in nude mice, and the resultant tumours resemble the primary CCS. The tumour cells and the cultured cells have melanosomes in their cytoplasm and are immunoreactive with the melanoma-specific antibody HMB45, but do not express S-100 protein. The cultured CCS cells have the t(12; 22)(q13; q12) translocation and express the hybrid EWS/ATF-1 gene. No transcripts of the hybrid gene were detected in a malignant cutaneous melanoma tested simultaneously. Although CCS and malignant melanoma are morphologically related, the present results suggest that their geneses differ at the chromosome and molecular levels. They also indicate that chromosome analysis and detection of fusion EWS/ATF-1 transcripts may be useful adjuvant tools for the diagnosis of CCS.

e22505Background: Leiomyosarcoma of bone (LMSoB) is a rare malignant bone tumor. Its clinical outcome has not been deeply assessed in the literature. This multicenter retrospective study was conduc...

10578Background: High dose Methotrexate (HDMTX) has been a key element of standard therapies for lymphatic malignancy (ML), osteosarcoma (OS), etc. Despite optimal supportive care, delayed MTX excr...

Renal cell carcinoma (RCC) is thought to respond unreliably to radiotherapy (RT). Zoledronic acid significantly reduces the risk of skeletal complications. This study investigated whether RT with zoledronic acid prolonged the time to bone-lesion progression in comparison with RT alone.Twenty-seven patients (34 lesions) with bone metastases secondary to RCC undergoing treatment with RT with or without zoledronic acid were retrospectively evaluated at two institutions between 1999 and 2009. Twelve patients were treated with RT alone from 1999 to 2008 (RT group). Fifteen patients were treated with RT and zoledronic acid from 2006 to 2009 (RT + Z group). The time to skeletal-related events and pain progression were assessed from patients' medical records.The median (range) follow-up was 26 (3-75) and 24 (3-55) months in the RT and RT + Z groups, respectively. Three patients (three lesions) in the RT + Z group had skeletal-related events (SREs). In contrast, six patients (eight lesions) in the RT group had SREs. SREs comprised pathological fractures in five, additional surgeries in three, spinal cord or cauda equine compression in two, and repeat RT in one. There was a significant difference in SRE-free survival time and duration of site-specific pain response between groups.RT combined with zoledronic acid significantly prolonged SRE-free survival and duration of pain response compared with RT alone in the treatment of osseous metastases from RCC.

TPS10575 Background: Based on the results of JCOG0304, which showed sufficient efficacy of perioperative chemotherapy with adriamycin plus ifosfamide (AI) for operable high-grade soft tissue sarcom...

Aim: T binds to the minor groove of DNA and blocks DNA repair machinery. In addition, T inhibits interactions of transcription factors with DNA. It has been reported that T is an active drug in TRS pts unresponsive to available chemotherapies with a significant increase in progression-free survival (PFS) and overall survival in study-C (ASCO 2014, Abstract: 10524). For pts with confirmed disease progression in best supportive care (BSC) arm of study-C, study-S as a rescue therapy was conducted to evaluate safety and efficacy of T. Efficacy for pts who were enrolled in both studies and efficacy difference for T between study-C and study-S were evaluated. Methods: Target population of study-C was pts with histologically proven TRS of 14 types and unresponsive or intolerable to standard chemotherapy. After confirmation of disease progression based on image assessments in study-C, pts who were assigned to BSC were enrolled in study-S if they signed a consent form. Pts received T as a 24-hour continuous infusion every 21 days. We analyzed intra-patient comparison between BSC in study-C (BSC/C) and T in study-S (T/S), and inter-patient comparison between T in study-C (T/C) and T/S. We used a multivariate Cox proportional hazard model adjusted by background factors to estimate hazard ratios (HRs) for PFS in these comparisons. Results: In study-C, 76 pts were randomized: 39 in T and 37 in BSC arm. Out of 37 pts in BSC arm of study-C, 31 pts were enrolled in study-S. Number of pts for efficacy analysis of T/C, BSC/C and T/S were 37, 29 and 29 respectively. Median PFS (95% confidence interval) for T/C, BSC/C and T/S were 5.6 month (m) (4.1-7.5), 0.9 m (0.9-1.0), and 7.3 m (2.9 -9.1), respectively. HRs for PFS in intra- (BSC/C vs T/S) and inter-patient (T/C vs T/S) comparison were 0.08 (P Conclusions: PFS was significantly prolonged in T/S compared with BSC/C, and was not different between T/C and T/S. Although contribution to survival is not evaluated, it is expected T could suppress progress of advanced TRS even at the late stage. Disclosure: T. Ueda: I disclose that I have a consultant or advisory relationship with Daiichi-Sankyo Pharmaceutical Co.Ltd.; A. Kawai: I disclose that I have received Honoraria from TAIHO, GSK, MSD and Eisai. All other authors have declared no conflicts of interest.

Primitive neuroectodermal tumors (PNET) occur either in the central nervous system (CNS; central PNET, cPNET) or in the peripheral sites (peripheral PNET, pPNET). Recent molecular approaches have been defining a new concept of PNET, that is, the pPNET including Ewing's sarcoma (ES) which expresses MIC2 glycoprotein and shows the specific chimeric gene of EWS-FLI1. The expression of MIC2 and the genetic rearrangement of EWS-FLI1 are considered to be highly specific to the pPNET/ES. This study examined the expression of MIC2 and EWS-FLI1 gene by means of immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) on various small round cell tumors originating in the CNS or non-CNS organs. All peripheral PNET tested expressed MIC2 and were positive for EWS-FLI1 (11/11). In contrast, all cPNET and other blastic CNS tumors were negative for MIC2: medulloblastoma (0/3), cerebral PNET (0/2), spinal PNET (0/2), glioblastoma (0/2), retinoblastoma (0/3), and pineoblastoma (0/2). These MIC2-negative tumors were also negative for the chimeric gene product of EWS-FLI1. Interestingly, one PNET originating in the intracranial dura mater was positive for both MIC2 and EWS-FLI1 fusion gene. The results indicate that cPNET lacks any genetic or protein markers, except for a meningeal PNET which falls into the same phenotypic spectrum of pPNET.

Peritoneal sarcomatosis was found in a 53-year-old male who had a history of resection of clear cell sarcoma (CCS) of the right wrist 7 years previously. Both the previous wrist tumor and the peritoneal disseminants consisted of small, spindle-shaped cells occasionally containing melanophages. Histologic features, histochemical demonstration of argentaffin granules, immunohistochemical reaction with HMB 45, and the demonstration of a chimeric transcript of EWS-ATF-1 established the diagnosis of CCS in the peritoneal tumors. As far as we are aware, this is the first case of a peritoneal sarcomatosis associated with CCS.

Synovial sarcoma is a clinically and morphologically well defined soft-tissue tumor that occurs predominantly in the extremities of adolescents and young adults. It tends to arise in the vicinity of large joints, especially the knee8. This tumor was designated synovial sarcoma because of its anatomical location and its histological resemblance to normal synovial tissue. However, we do not believe that there is any convincing evidence that synovial sarcoma always originates from synovial tissue. It is possible that the lesion sometimes arises from primitive mesenchymal cells rather than from preformed synovial cells; therefore, the development of synovial sarcoma is no longer thought to require the presence of preexisting synovial tissue. To the best of our knowledge, there have been no reports of synovial sarcoma arising in bone. The reciprocal translocation t(X;18)(p11.2;q11.2) was noted in all twenty-two reported cases of synovial sarcoma that have been studied cytogenetically5,18. This translocation is considered to be specific to this tumor. Cloning of the DNA adjacent to the breakpoints of the translocation t(X;18) has shown2 that this translocation results in fusion of the SYT gene at 18q11.2 to either of two genes, SSX1 or SSX2, at Xp11.2. This rearranged configuration of DNA is transcribed to messenger RNA and is called a chimeric SYT-SSX transcript. A chimeric SYT-SSX transcript does not occur normally and thus provides a specific marker for synovial sarcoma that can be detected with reverse transcriptase-polymerase chain-reaction testing. We describe the case of a patient who had synovial sarcoma of bone that was verified by the detection of a chimeric SYT-SSX transcript. A sixty-seven-year-old man had a four-month history of pain in the right wrist when he was first seen by us. Physical examination revealed moderate swelling and a restricted range of motion of the wrist (30 …

SCA6 is an autosomal dominant spinocerebellar ataxia (SCA) caused by a small CAG repeat expansion of the gene encoding an alpha-1A-voltage-dependent Ca channel gene subunit on chromosome 19p13. A Japanese woman with SCA6, with a 7-year history of progressive pure cerebellar ataxia, died of malignant lymphoma. Systematic neuropathological examination showed that neuronal degeneration was confined to the cerebellar Purkinje cells and, to a lesser degree, the granular cells, without any involvement of other central nervous system structures. Such pathological selectivity correlates with the localized expression of the responsible gene, and coincides with the neurological manifestation. These findings might contribute to establishing the phenotype of the SCA6 via comparison with other dominant ataxias.

Background: Bone and soft tissue sarcomas (BSTS) are rare malignant tumors. Recently, the combination of gemcitabine and docetaxel (GD) was shown to have activity as second-line setting in BSTS. However, the efficacy as first-line and adjuvant settings and precise profiles of adverse events in Japanese patients are not known yet. In the present study, the feasibility and efficacy of GD in patients with BSTS were investigated. Methods: Patients with BSTS treated with GD in our institutions were retrospectively analyzed. Information regarding clinical features, adverse events, and outcome was collected and statistically studied. Factors related to survival were analyzed using log-rank test and Cox proportional hazard regression method. Results: A total of 134 patients were analyzed. GD was carried out as adjuvant setting in 9, first-line in 23, second-line in 56, and third-or-greater line in 46 patients. The response rate (RR) for all patients was 9.7%. RR for the patients treated as adjuvant or first-line setting was 18.8%, whereas that as second-or-greater line was 6.9%. The median progression-free survival (PFS) and overall survival (OS) of all patients were 4.8 (95% CI 3.5–6.1) and 16.4 (95% CI 9.8–22.9) months, respectively. Survival tended to be better in the patients treated as first-line than in those treated as second-or-greater line. Multivariate analysis demonstrated that history of prior chemotherapy (p = 0.046) and response to GD (p = 0.009) was significantly associated with PFS and OS, respectively. The leucopenia and neutropenia were the most frequent adverse events, and grade 3 or 4 leucopenia and neutropenia were observed in 69.4 and 72.4% of the patients. Grade 2 or 3 pneumonitis was observed in one (0.7%) and four (3.0%) patients, respectively. All the patients with pneumonitis had experienced prior chemotherapy and/or radiotherapy. Conclusions: GD used as both first- and second/later line is effective chemotherapy for a proportion of patients with advanced BSTS. Higher response rate and better outcome was achieved in chemotherapy-naïve patients. This regimen is associated with high incidence of severe hematological toxicity, as well as the risk of severe pneumonitis, especially in pre-treated patients. GD is promising for further analysis by phase III study for the patients with BSTS.