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Tomoki Nakamura,1 Kunihiro Asanuma,1 Motoshi Takao,2 Takashi Yamanaka,3 Hiroshi Koike,4 Toyofumi F Chen-Yoshikawa,5 Satoshi Tsukushi,6 Hiroaki Kuroda,7 Eiji Kozawa,8 Masaaki Sano,9 Hisaki Aiba,10 Ryoichi Nakanishi,11 Akihito Nagano,12 Kenji Yamada,13 Yoji Shido,14 Katsuhisa Kawanami,15 Yuya Izubuchi,16 Akihiro Sudo,1 Yoshihiro Nishida4,17 1Department of Orthopedic Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan; 2Department of Thoracic Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan; 3Department of Radiology, Mie University Graduate School of Medicine, Tsu, Mie, Japan; 4Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; 5Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; 6Department of Orthopedic Surgery, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan; 7Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan; 8Department of Orthopedic Surgery, Nagoya Memorial Hospital, Nagoya, Aichi, Japan; 9Department of Thoracic Surgery, Nagoya Memorial Hospital, Nagoya, Aichi, Japan; 10Department of Orthopedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Aichi, Japan; 11Department of Oncology, Immunology and Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Aichi, Japan; 12Department of Orthopedic Surgery, Gifu University Graduate School of Medicine, Gifu, Gifu, Japan; 13Department of Musculoskeletal Oncology, Okazaki City Hospital, Okazaki, Aichi, Japan; 14Department of Orthopedic Surgery, Hamamatsu Medical University, Hamamatsu, Sizuoka, Japan; 15Department of Orthopedic Surgery, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan; 16Department of Orthopedics and Rehabilitation Medicine, University of Fukui Faculty of Medical Sciences, Eiheiji, Fukui, Japan; 17Department of Rehabilitation, Nagoya University Hospital, Nagoya, Aichi, JapanCorrespondence: Tomoki NakamuraDepartment of Orthopaedic Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, JapanTel +81592315022Fax +81592315211Email tomoki66@med.mie-u.ac.jpPurpose: Here, we investigated the oncological outcomes of lung metastasectomy and/or radiofrequency ablation (RFA) of 92 patients with soft tissue sarcoma (STS) at nine institutions.Methods: The study cohort included 65 men and 27 women with a mean age of 59 years at the time of metastasis. The mean follow-up duration was 51 months. All patients underwent metastasectomy and/or RFA for lung metastasis.Results: The mean maximum size of the initial lung metastasis was 14.6 mm. At the initial evaluation, 41 patients had a single metastasis, whereas 51 patients had multiple metastases. The mean number of metastasectomies and/or RFA was 2 per patient. A total of 70 patients underwent lung metastasectomy, whereas the other 13 underwent lung RFA. The remaining nine patients underwent both RFA and metastasectomy. The 5-year post-metastatic survival rate was 52%. The patients who underwent complete treatment for the initial metastasis had better post-metastatic survival rates than those who underwent incomplete treatment. A univariate analysis of all possible prognostic factors for complete treatment confirmed the predictive value of disease-free interval, metastasis at initial presentation, distribution, tumor size, and number of lung metastases. Of the 92 patients, 74 underwent complete treatment for initial metastasis; in these patients, univariate and multivariate analyses showed that a smaller tumor size and single-lung metastasis were prognostic factors for superior post-metastatic survival. The patients with a smaller (< 11.5 mm) single metastasis had better post-metastasis survival. The 5-year post-metastatic survival rates were 89.9% for patients with a smaller (< 11.5 mm) single metastasis versus 22.7% for patients with larger (> 11.5 mm) and multiple metastases.Discussion: We propose that complete treatment for lung metastasis in patients with STS may improve post-metastatic survival rates. Furthermore, tumor number and size are important variables for clinical decision-making.Keywords: lung metastasis, metastasectomy, radiofrequency ablation, soft tissue sarcoma

Unlabelled: Granular cell tumors are uncommon but typically histologically benign neoplasms that occasionally behave as malignant tumors. Differentiation of benign granular cell tumors from malignant counterparts with radiographic and/or histologic analysis is crucial for physicians. We retrospectively studied five cases of intramuscular granular cell tumors arising in the lower extremities. All tumors had been histologically diagnosed as benign and were resected with a wide surgical margin. The minimum followup was 1 year (mean, 45 months; range, 12-119 months) after surgery. Four patients had no local recurrence or distant metastasis (at a minimum of 18 months followup), whereas one patient with lymph node metastasis had a recurrence and distant metastasis 3 months after surgery resulting in death. Intramuscular granular cell tumors can be diagnosed based on their characteristic MRI features, such as peripheral high intensity on T2-weighed images, and histologic evaluation. The histologic criteria described by Fanburg-Smith et al. can differentiate malignant granular cell tumors from benign tumors. A wide resection seems suitable for most granular cell tumors in the extremities.Level Of Evidence: Level IV, diagnostic study. See the Guidelines for Authors for a complete description of evidence. [ABSTRACT FROM AUTHOR]

The optimal timing of surgery and the number of courses of perioperative chemotherapy for high-risk soft tissue sarcoma patients are still controversial. Tumour growth during neoadjuvant chemotherapy led to limb amputation in some patients. This study aims to confirm the non-inferiority of surgery and three courses of adjuvant chemotherapy with adriamycin (30 mg/m2, days 1 and 2) plus ifosfamide (2 g/m2, days 1-5) compared with our standard treatment of three courses of neoadjuvant chemotherapy and surgery followed by two courses of adjuvant chemotherapy with adriamycin plus ifosfamide for localized high-risk soft tissue sarcoma patients. This is a multi-center, two-arm, open-label, randomized phase III trial. The primary aim is to confirm the non-inferiority in overall survival (margin: hazard ratio of 1.61). This is the first randomized controlled trial to compare neoadjuvant chemotherapy and immediate surgery for soft tissue sarcoma. This trial was initiated on 16 November 2022 and registered with the Japan Clinical Trials Registry (jRCTs031220446)., (© The Author(s) 2024. Published by Oxford University Press.)

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., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background/aim: Complete surgical resection with negative margins remains the cornerstone for curative treatment of rectal cancer; however, local recurrence can pose a significant challenge. Herein, we aimed to introduce a novel surgical technique for combined resection of the pubic arch and ischial bone in the context of treating recurrent rectal cancer., Case Report: We present a case of a patient with a fourth local recurrence of rectal cancer, with no evidence of distant metastasis. The tumor directly invaded the posterior wall of the pubic arch. To achieve complete tumor resection, an osteotomy was performed using a thread wire saw at the bilateral pubic rami and ischial bones. Intraoperative frozen section analysis (rapid tissue examination) was conducted on tissue samples from the lateral margins of the planned osteotomy line. Samples were negative for adenocarcinoma (cancerous cells). The combined resection of the pubic arch and ischial bone was successfully performed with negative margins for adenocarcinoma, as confirmed by frozen section analysis., Conclusion: Mastery of the surgical technique for combined resection of the pubic arch and ischial bone may be clinically significant for achieving complete resection in cases of multiple resections for locally recurrent rectal cancer., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Reconstruction after periacetabular bone tumor resection involves important tradeoffs; large bone grafts or endoprostheses are reported to offer fair walking function in general but can be technically demanding and carry a high risk of severe complications. Conversely, hip transposition avoids implant-related risks, but stability and functional return may be less consistent. Fewer studies are available on hip transposition, which is also appealing in more resource-constrained environments, and little is known about the time course from surgery to functional return after hip transposition., Questions/purposes: (1) What is the time course of recovery of walking function after hip transposition, especially in the first 6 months? (2) What factors are associated with a greater likelihood of early functional recovery? (3) Is early (2-month) functional recovery associated with a greater likelihood of walking ability and higher Musculoskeletal Tumor Society (MSTS) scores?, Methods: Between 2009 and 2019, six tertiary care centers in Japan treated 48 patients with internal hemipelvectomy for malignant tumors. During that time, the preferred reconstructive approach was hip transposition, and 92% (44 of 48) of our patients were treated with this procedure. Among them, 86% (38 of 44) had follow-up of at least 6 months, had no local recurrence during that time, and were included in our retrospective study. We chose 6 months as the minimum follow-up duration because the endpoints in this study pertained to early recovery rather than reconstructive durability. Hip transposition involved moving the proximal end of the femur (femoral head, resection end of the trochanteric area, and spacers such as prostheses) upward to the underside of the resected ilium or the lateral side of the sacrum if sacroiliac joint resection was performed. The end of the proximal femur was stabilized to the remaining ilium or sacrum using polyethylene tape, polyethylene terephthalate mesh, an iliotibial tract graft, or an external fixator, according to the surgeon's preference. The median age at surgery was 46 years (range 9 to 76 years), there were 23 women and 15 men, and the median follow-up duration was 17 months (range 6 to 110 months). The postoperative time course of functional recovery was assessed with a record review, the timing of functional milestones was identified (wheelchair, walker, bilateral crutches, single crutch or cane, and walking without an aid), and the MSTS score at the final follow-up was assessed. Additionally, demographic and surgical factors were reviewed, and their association with short-term functional recovery and the final functional outcome was analyzed., Results: Patients started using a walker at median postoperative day (POD) 20 (IQR 14 to 36) and with bilateral crutches at median POD 35 (IQR 20 to 57). At POD 60, which was the approximate median date of discharge, 76% (29 of 38) of patients were able to walk using bilateral crutches (the early recovery group) and 24% (nine of 38) of patients were not able to do so (the delayed recovery group). No baseline factors were different between the two groups. The early recovery group had a higher median MSTS score than the delayed recovery group: 57% (range 17% to 90%) versus 45% (13% to 57%) (p = 0.047). Moreover, more patients acquired better function (a single crutch or cane or more) in the early recovery group, with a median of 5 months (95% CI 4 to 11) than did those in the delayed recovery group (median not reached) (p = 0.0006). The HR was 15.2 (95% CI 2.5 to 93). Forty-two percent (16 of 38) underwent additional surgery for wound management., Conclusion: It took patients a fair amount of time to recover walking function after hip transposition, and patients who could not walk on bilateral crutches at POD 60 seemed less likely to regain walking function and were likely to have lower MSTS scores thereafter. Wound-related complications were frequent. This method may be a realistic alternative for younger patients who have the strength for a long rehabilitation period or those who want to minimize prosthesis-related complications. Future studies with more patients are necessary to understand the risk factors associated with delayed recovery.Level of Evidence Level III, therapeutic study., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, and patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research ® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2023 by the Association of Bone and Joint Surgeons.)

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., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2023 by the Association of Bone and Joint Surgeons.)

Background: This retrospective study aimed to demonstrate surgical operative approach of total pelvic exenteration combined with sacral resection with rectal cancer and elucidate the relationships between the level of sacral resection and short-term outcomes., Methods: Twenty cases were selected. Data regarding sex, age, body mass index, neoadjuvant therapy, location of sacral resection ("Upper" or "Lower" relative to the level between the 3rd and 4th sacral segment), operative time, bleeding, and curability (R0/R1) were collected and compared to determine their association with complications exhibiting a Clavien-Dindo grade III., Results: The complication rate was significantly higher for recurrent cancers (n = 10, 76.9%) than for primary cancers (n = 1, 14.3%) ( P = .007), and for "Upper" resection (n = 8, 72.7%) than for "Lower" resection (n = 3, 33.3%) ( P = .078). Significant differences were observed when complication rates for "Lower" and primary cancer resection (n = 3, .0%) were compared between "Upper" and recurrent cancers (n = 8, 100.0%) ( P = .007)., Conclusion: In patients with recurrent rectal cancer, "Upper" sacral resection during total pelvic exenteration is associated with a high complication rate, highlighting the need for careful monitoring., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. FundingThe author(s) received no financial support for the research, authorship, and/or publication of this article. Availability of Data and MaterialsThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Aim: This multicenter retrospective study aimed to clarify the surgical and oncological outcomes of patients with high-grade soft tissue sarcoma (STS) who underwent prosthetic replacement reconstruction after lower extremity tumor resection., Patients and Methods: We retrospectively collected the data of 27 patients with high-grade STS. The mean follow-up duration after prosthetic replacement was 44.7 months., Results: The mean age at surgery was 63 years. The mean tumor size was 16 cm. For reconstruction, proximal femur replacement was performed in 15 patients, distal femur replacement in six, and total femur replacement in six. The major complications were infections in nine patients and aseptic loosening in four. Nine patients developed local recurrence. The cause of revision surgery was infection in five patients, aseptic loosening in three, and metal allergy in one. The 5-year prosthetic survival rate was 51.1%. At the final follow-up, amputation was performed in five patients. The 5-year limb salvage rate was 76.8%. The mean functional score of the 25 patients who could be assessed was 16.0 (53%). Of the 27 patients, five were excluded from the survival analysis because they underwent prosthetic replacement for local recurrence. The 5-year overall survival rate in the remaining 22 patients was 45.3%., Conclusion: We identified a high rate of surgical complications and poor survival in patients with high-grade STS who underwent tumor resection and reconstruction using prosthetic replacement of the lower extremities, although limb salvage was achieved in 81.5% of the patients. Careful follow-up is needed for surgical complications and oncological events after surgery., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft-tissue tumors. Intracranial metastasis from MPNSTs is quite rare., Observations: The authors report on a 73-year-old male whose MPNST metastasized to the brain and a 32-year-old male with leptomeningeal metastasis from MPNST and review 41 cases of MPNST that developed intracranial metastasis, as reported in the literature., Lessons: Brain metastasis and leptomeningeal metastasis of MPNSTs show different clinical courses and require pathology-specific treatment.

Background: Soft tissue sarcomas (STS) are a rare type of malignancy comprising a variety of histological diagnoses. Chemotherapy constitutes the standard treatment for advanced STS. Doxorubicin-based regimens, which include the administration of doxorubicin alone or in combination with ifosfamide or dacarbazine, are widely accepted as first-line chemotherapy for advanced STS. Trabectedin, eribulin, pazopanib, and gemcitabine plus docetaxel (GD), which is the empirical standard therapy in Japan, are major candidates for second-line chemotherapy for advanced STS, although clear evidence of the superiority of any one regimen is lacking. The Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group (JCOG) conducts this trial to select the most promising regimen among trabectedin, eribulin, and pazopanib for comparison with GD as the test arm regimen in a future phase III trial of second-line treatment for patients with advanced STS., Methods: The JCOG1802 study is a multicenter, selection design, randomized phase II trial comparing trabectedin (1.2 mg/m 2 intravenously, every 3 weeks), eribulin (1.4 mg/m 2 intravenously, days 1 and 8, every 3 weeks), and pazopanib (800 mg orally, every day) in patients with unresectable or metastatic STS refractory to doxorubicin-based first-line chemotherapy. The principal eligibility criteria are patients aged 16 years or above; unresectable and/or metastatic STS; exacerbation within 6 months prior to registration; histopathological diagnosis of STS other than Ewing sarcoma, embryonal/alveolar rhabdomyosarcoma, well-differentiated liposarcoma and myxoid liposarcoma; prior doxorubicin-based chemotherapy for STS, and Eastern Cooperative Oncology Group performance status 0 to 2. The primary endpoint is progression-free survival, and the secondary endpoints include overall survival, disease-control rate, response rate, and adverse events. The total planned sample size to correctly select the most promising regimen with a probability of > 80% is 120. Thirty-seven institutions in Japan will participate at the start of this trial., Discussion: This is the first randomized trial to evaluate trabectedin, eribulin, and pazopanib as second-line therapies for advanced STS. We endeavor to perform a subsequent phase III trial comparing the best regimen selected by this study (JCOG1802) with GD., Trial Registration: This study was registered with the Japan Registry of Clinical Trials ( jRCTs031190152 ) on December 5, 2019., (© 2023. The Author(s).)

The purpose to the present study is to research the association between age at surgery and survival outcomes of patients with sarcoma in head and neck. Twenty-six patients with head and neck sarcoma who underwent by surgery from 2003 to 2017 were enrolled in the present observation study. Patients who did not undergo chemotherapy were significantly older age at surgery by Mann-Whitney U test. Fifty-five was the cutoff age that predicted death by receiver operating curve analysis. Shorter survival rates of overall, disease-specific, local recurrence-free and disease-free were associated with older age by log-rank test. Age (≥55 years/<55 years) was correlated with shorter overall survival by multivariate analysis of Cox's proportional hazards model adjusting with chemotherapy (absence/presence). In conclusion, older age predicts worse overall survival in head and neck sarcoma., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

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., (© 2022. The Author(s).)

Affinos (Kuraray, Japan) is a β-tricalcium phosphate bone substitute with a unidirectional porous structure. This study aimed to investigate its efficacy on the healing process after filling for bone defects. Fifty-six patients who met the inclusion criteria were divided into cohort 1 (n = 30), including bones other than phalanges and metacarpal/tarsal bones, and cohort 2 (n = 26), including phalanges and metacarpal/tarsal bones. Semi-quantified scores for material resorption and trabeculation through the defect were evaluated with radiographs after surgery. In some patients, levels of bone metabolic markers were assessed. The values of resorption and trabeculation increased steadily with time, and trabeculation progressed compared with resorption in both cohorts. In cohort 1, multiple regression analyses showed that the diaphyseal lesion, smaller defect volume, and increased resorption values at 3 months were associated with increased values of resorption 12 months after surgery (R 2  = 0.66, p < 0.001). The trabeculation values at 2 months were positively related to the trabeculation values 12 months after surgery (R 2  = 0.35, p = 0.002). In cohort 2, the increased resorption values at 2 months and smaller defect volume significantly correlated with the increased resorption values 12 months after surgery (R 2  = 0.58, p < 0.001). The ratio from the baseline of pyridinoline cross-linked carboxyterminal telopeptide of type I collagen at 3 months was negatively associated with the trabeculation values 12 months after surgery (R = - 0.791, p = 0.004). Evaluation of radiographic images and bone metabolic markers in the early postoperative period may predict the healing status at 12 months postoperatively in the defects followed by Affinos filling., (© 2022. The Author(s).)

Objectives: The aim of JCOG1610 (randomized controlled phase III trial) was to confirm the superiority of preoperative denosumab to curettage with adjuvant local therapy for patients with giant cell tumor of bone without possible post-operative large bone defect., Methods: The primary endpoint was relapse-free survival and the total sample size was set at 106 patients. Patient accrual began in October 2017. However, the accrual was terminated in December 2020 due to a recommendation from the Data and Safety Monitoring Committee because of poor patient accrual. Now, we report the descriptive results obtained in this study., Results: A total of 18 patients had been registered from 13 Japanese institutions at the time of termination on December 2020. Eleven patients were assigned to Arm A (curettage and adjuvant local therapy) and 7 to Arm B (preoperative denosumab, curettage and adjuvant local therapy). Median follow-up period was 1.6 (range: 0.5-2.8) years. Protocol treatment was completed in all but one patient in Arm A who had a pathological fracture before surgery. All patients in Arm B were treated with five courses of preoperative denosumab. Relapse-free survival proportions in Arm A and B were 90.0% (95% confidence interval: 47.3-98.5) and 100% (100-100) at 1 year, and 60.0% (19.0-85.5) and 62.5% (14.2-89.3) at 2 years, respectively [hazard ratio (95% confidence interval): 1.51 (0.24-9.41)]., Conclusion: In terms of relapse-free survival, the superiority of preoperative denosumab was not observed in patients with giant cell tumor of bone without possible post-operative large bone defect., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The high rate of aseptic loosening of cemented stems has led to their frequent use in endoprosthetic reconstruction. However, problems, such as stem breakage and stress shielding at the insertion site, remain. The Japanese Musculoskeletal Oncology Group (JMOG) has developed Kyocera Modular Limb Salvage System (KMLS) cementless stems with a unique tapered press-fit and short fixation design. This study aimed to clarify the short-term postoperative outcomes of this prosthesis and validate the stem design., Methods: One hundred cases of KMLS cementless stems (51 male patients; median age, 49 years; mean follow-up period, 35 months), with a minimum follow-up of 2 years, for the proximal femur (PF), distal femur (DF), and proximal tibia were prospectively registered for use. Prosthesis survival, complication rates, postoperative functional, and radiographical evaluation were analyzed. Complications or failures after insertion of the KMLS endoprostheses were classified into five types and functional results were analyzed according to the MSTS scoring system at postoperative 1 year. The diaphyseal interface and anchorage were graded by the ISOLS system at postoperative 2 years., Results: The overall prosthesis survival rates at 2 and 4 years were 88.2 and 79.6%, respectively. The prosthesis-specific survival rate excluding infection and tumor recurrence was 90.2 and 87.9%, respectively. Younger age (p = 0.045) and primary tumor (p = 0.057) were associated with poor prognosis of prosthesis-specific survival excluding infection and tumor recurrence. Complications were observed in 31 patients, 13 patients underwent revision surgery. The mean MSTS functional score at 1 year postoperatively was 68%. Early implant loosening was significantly more common in the DF (p = 0.006) and PF/DF straight stem (p = 0.038). The ISOLS radiographic evaluation at 2 years after surgery revealed good bone remodeling and anchorage in most cases (bone remodeling: 90% / excellent and good, anchorage: 97% / excellent and good)., Conclusions: Tumor endoprosthesis long-term fixation to the diaphysis of the lower extremity remains challenging. The KMLS cementless stem with a unique tapered press fit design showed good short-term results in maintaining bone stock. To prevent early loosening, a curved stem should be used in PF and DF, but long-term follow-up is necessary., (© 2022. The Author(s).)

Chondrosarcoma is the second most common primary malignant bone tumor. In this multicenter study, we sought to evaluate the disease-specific survival (DSS) and disease-free survival (DFS), and prognostic factors in patients with dedifferentiated chondrosarcoma (DDCS) or grade 3 chondrosarcoma (G3CS) in Japan. We retrospectively investigated the treatment outcomes and prognostic factors in 62 patients with DDCS and 19 patients with G3CS at 15 institutions participating in the Japanese Musculoskeletal Oncology Group. We also clarified significant clinicopathological factors for oncological outcomes. In surgery for primary lesions aimed at cure, a histologically negative margin (R0) was obtained in 93% (14/15) of patients with G3CS and 100% (49/49) of patients with DDCS. The 5-year DSS was 18.5% in patients with DDCS and 41.7% in patients with G3CS (p = 0.13). Local control was obtained in 80% (12/15) and 79.6% (39/49) of patients with G3CS and DDCS in the primary lesion after surgery with a wide surgical margin, respectively. In multivariate analysis, stage and no treatment/palliative treatment for the primary lesion were independent prognostic factors for DSS of DDCS, and age and no treatment/palliative treatment for DSS of G3CS. The 5-year DFS rate was 22.8% in 26 patients with DDCS who did not receive adjuvant chemotherapy, and 21.4% in 14 patients who received adjuvant chemotherapy. The prognosis of DDCS remains poor, although R0 resection was carried out in most cases. Effective and/or intensive chemotherapeutic regimens or agents should be considered or developed for patients with high-grade chondrosarcoma, particularly for those with DDCS., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

This study aimed to retrospectively analyze the clinical outcomes of patients with pelvic and retroperitoneal bone and soft tissue sarcoma (BSTS). Overall, 187 patients with BSTS in the pelvis and retroperitoneal region treated at 19 specialized sarcoma centers in Japan were included. The prognostic factors related to overall survival (OS), local control (LC), and progression-free survival (PFS) were evaluated. The 3-year OS and LC rates in the 187 patients were 71.7% and 79.1%, respectively. The 3-year PFS in 166 patients without any distant metastases at the time of primary tumor diagnosis was 48.6%. Osteosarcoma showed significantly worse OS and PFS than other sarcomas of the pelvis and retroperitoneum. In the univariate analyses, larger primary tumor size, soft tissue tumor, distant metastasis at the time of primary tumor diagnosis, P2 location, chemotherapy, and osteosarcoma were poor prognostic factors correlated with OS. Larger primary tumor size, higher age, soft tissue tumor, chemotherapy, and osteosarcoma were poor prognostic factors correlated with PFS in patients without any metastasis at the initial presentation. Larger primary tumor size was the only poor prognostic factor correlation with LC. This study has clarified the epidemiology and prognosis of patients with pelvic and retroperitoneal BSTS in Japan.

Background: These clinical practice guidelines are intended to provide recommendations based on the best evidence obtained to date on key issues in clinical practice to improve the prognosis, diagnostic and therapeutic processes for patients with soft tissue tumors., Methods: The Guidelines Development Committee and Systematic Review Committee were composed of a multidisciplinary team of specialists who play an important role in soft tissue tumor care. Clinical questions (CQs) were determined by choosing key decision-making points based on Algorithms for the diagnosis and treatment of soft tissue tumors. The guidelines were developed according to the "Medical Information Network Distribution Service (Minds) Handbook for Clinical Practice Guideline Development 2014" and "Minds Manual for Clinical Practice Guideline Development 2017." Recommendation strength was rated on two levels and the strength of evidence was rated on four levels. The recommendations were decided based on agreement by 70% or more voters., Results: Twenty-two CQs were chosen by the Guidelines Development Committee. The Systematic Review Committee reviewed the evidence concerning each CQ, a clinical value judgment was added by experts, and the text of each recommendation was determined., Conclusion: We established 22 CQs and recommendations for key decision-making points in the diagnosis and treatment of soft tissue tumors according to the Minds Clinical Practice Guideline development methods. We hope that these guidelines will assist the decision-making of all medical staff engaged in the treatment and diagnosis of soft tissue tumors, and eventually lead to improved soft tissue tumor care in the country., Competing Interests: Declaration of competing Interest Akira Kawai reports research grants from Daiichi-Sankyo, Eli-Lilly, Taiho, Takara-Bio and Japanese Orthopaedic Association. Hirotaka Kawano reports honoraria from Daiichi Sankyo and Hisamitsu, and research grants from Japanese Orthopaedic Association, Nakatomi Foundation, Daiichi-Sankyo, Kyocera, Shionogi, Teijin, Zimmer Biomet, Johnson and Johnson, Smith and Nephew, Peter Blehm Japan and Stryker Japan. Toshiyuki Kunisada reports a research grant from Kuraray, and the Department of Medical Materials for Musculoskeletal Reconstruction is an endowment department, supported with an unrestricted grant from Kyocera. Shunji Takahashi reports honoraria from Eisai, Novartis, Taiho, Astrazeneca, Chugai, Bayer, Daiichi-Sankyo, and research grants from EISAI, Novartis, Taiho, Astrazeneca, Chugai, Bayer, Daiichi-Sankyo, Ono pharmaceutical, IQVIA and Bristol-Myers-Squib. Kazuhiro Tanaka belongs to an endowment department supported with grants from Teijin Nakashima Medical Co., Ltd. and Meditec Co., Ltd. Norio Yamamoto belongs to an endowed department supported with grants from Zimmer Biomet G.K. and Hisamitsu Pharmaceutical Co., Inc., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The distal femur is a common site of bone tumors. After surgical resection, prosthetic replacement is a major reconstruction method. We aimed to elucidate the long-term outcomes of the Kyocera Modular Limb Salvage (KMLS) systems after resection of tumors in the distal part of the femur., Methods: Between 1998 and 2014, 125 patients were treated at 14 institutions. There were 59 males and 66 females, with a mean age of 35 years. The mean follow-up period was 132 months., Results: There had been 65 additional surgeries, including 56 revisions and 9 amputations: 15 for aseptic loosening, 14 for stem breakage, 13 for deep infection, 13 for rotator-hinge bushing failure, 5 for local recurrence, and 5 for others. Implant survival rates at 10 and 15 years were 58.5% and 39.4%. The cumulative incidence of 15-year revision for femoral stem breakage was 31.7% in patients with cementless fixation. The 15-year cumulative incidence of revision for aseptic loosening was 19.8% in patients with cement fixation., Conclusions: KMLS systems represent a reliable system with long-term results. Stem breakage should be considered in patients with cementless and/or smaller femoral stem sizes. Aseptic loosening should be considered in patients with cement systems after 10 years.

Background: This systematic review assessed and compared the efficacy of marginal resection to wide resection in patients with atypical lipomatous tumours (ALT) by evaluating the local recurrence rates, overall survival and adverse event rates., Methods: We evaluated studies published between 1 January 1990 and 31 January 2019. The risks of bias in the selected studies were analyzed using the Cochrane Collaboration Risk of Bias Tool. The quality of the evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation approach., Results: Three case-control studies and three case series studies were identified. A meta-analysis was performed of six studies to evaluate the local recurrence rate after resection. Comparison of marginal and wide resections showed that the local recurrence rate was not significantly higher in the marginal resection group (14.2 and 1.4%, odds ratio: 2.88, 95% confidence interval 0.99-8.33, P = 0.05). We observed no difference in overall survival. In one study, the rates of adverse events were 14.7% in the marginal resection group and 45.4% in the wide treatment group (odds ratio, 0.32; 95% confidence interval 0.11-80.91, P < 0.05)., Conclusions: In our analyses, five of six studies reported no recurrence for wide resection, compared to three to seven recurrences in the marginal resection group. One study reported only one case of recurrence for wide resection. Because ALT has a relatively good prognosis, the use of marginal resection is acceptable to preserve musculoskeletal function., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: Soft tissue sarcomas (STS) are rare, and little is known about the factors that affect the delays in the initial treatment. The aim of this study is to quantify the period between onset of symptoms and start of treatment of STS and determine the factors affecting delays in initial treatment. Methods: This is a retrospective study of all STS treated in our institution between October 2009 and March 2019. We analysed patient record to determine the period from onset of symptoms to start of initial treatment. We also collected data with regard to patient characteristics and features of the tumour. Tumours were classified into upper extremity, lower extremity, trunk and others based on location of the tumour. Statistical tests were done to identify factors that affected delay in initial treatment. Results: The study included 134 patients (76 male and 58 female) with STS with an average age of 56.6 years. The tumours involved the upper extremity in 20 patients, lower extremity and trunk in 50 patients each and other areas in 14 patients. The most frequent histological subtypes were liposarcomas ( n = 31, 23.5%) and undifferentiated pleomorphic sarcomas ( n = 24, 18.2%). Initial treatment was delayed by an average of 9.9 months for all groups. The period of treatment delay for tumours involving the upper extremity was shorter (7.9 months) and these tumours were smaller at initial presentation (57.6 mm) compared to tumours in other locations ( p < 0.05). Other factors that were positively associated with treatment delays were a history of diabetes mellitus ( p = 0.037) and smoking ( p = 0.026). Conclusion: Patients with upper-extremity STS may have the benefit of a relatively better prognosis as they present earlier and with a smaller tumour. In addition, factors, such as diabetes and smoking, which indicate a low interest in health also influenced the delay in the initial treatment. Level of Evidence: Level III (Therapeutic).

Background: The optimal procedure for functional reconstruction of the extensor mechanism after proximal tibia mega-prosthetic replacement remains unclear., Methods: Since 2006, 14 consecutive patients with aggressive bone tumors in the proximal tibia who underwent mega-prosthetic replacement were prospectively treated with reconstruction of the extensor mechanism using an ipsilateral iliotibial band. The surgical procedure consisted of wrapping the reversed iliotibial band around the tibia component, firmly suturing it to the remaining patellar tendon and tibialis anterior fascia, and covering it with a muscle flap. At the last follow up, the function was assessed based on extensor lag, active flexion of the knee, and Musculoskeletal Tumor Society score. Patellar height was measured with the Insall-Salvati ratio (ISR) preoperatively, postoperatively, and at the last follow up., Results: At the last follow up, the extensor lag and active flexion in 14 patients averaged 2.5° and 86°, respectively. Musculoskeletal Tumor Society score could be obtained in nine surviving patients at the last follow up and was a mean of 20.7 points. The mean ISR preoperatively, postoperatively, and at the last follow up was 1.04, 0.75, and 0.89, respectively. The extensor lag was not associated with the ISR value at any points, while reduced active flexion significantly correlated with a low ISR at the last follow up (P = 0.015). Four patients underwent additional surgeries due to postoperative infection, but none required eventual revision or amputation., Conclusion: The extensor mechanism reconstruction with the reverse transferred iliotibial band for mega-prosthetic replacement after proximal tibia resection yielded reliable outcomes with functional benefit to stabilize active knee extension., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In recent years, denosumab has been used to treat giant cell tumour of bone (GCTB) not only in cases where surgery is complicated but also preoperatively to decrease the preoperative grade or to facilitate surgery for Campanacci grade II and III cases. However, there are no clear protocols regarding the preoperative use of denosumab before en bloc resection. There are a few reports of recurrent cases after en bloc resection; however, the association with the use of denosumab is unknown. We present the clinical, radiological and histopathological findings of a case of Campanacci grade III GCTB at the distal end of the ulna, which resulted in soft tissue recurrence after en bloc resection with the preoperative use of denosumab., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Osteochondral destruction and a high recurrence rate after surgery are major concerns that make difficult the treatment course of tenosynovial giant cell tumor. The aims of this study were to elucidate rates of postoperative local recurrence and osteochondral destruction, as correlated with various demographic factors. Eighty surgically treated patients with intra-articular tumors (knee: 49, ankle and foot: 12, hip: 10, others: 9) were included in this study. Factors including age, disease type (diffuse/localized), location, existence of osteochondral destruction were correlated with local recurrence or development/progression of osteochondral destruction. The 5-year local recurrence free survival rate was 71.4%. Diffuse type (n = 59, localized: n = 21) (P = 0.023) and knee location (P = 0.002) were independent risk factors for local recurrence. Diffuse type (P = 0.009) was a significant risk factor, and knee location (P = 0.001) was a negative factor for osteochondral destruction at the initial examination. Progression of osteochondral destruction was observed more often in cases with local recurrence (P = 0.040) and findings of osteochondral destruction at the initial examination (P = 0.029). Diffuse type is a factor that should be noted for both local recurrence and osteochondral destruction, while local recurrence occurs but osteochondral destruction is less observed in the knee., (© 2021. The Author(s).)

Several types of soft tissue sarcomas have peripheral infiltrative growth characteristics called tail-like lesions. The efficacy of neoadjuvant therapy for tumors with tail-like lesions has not been elucidated. From 2012 to 2019, we analyzed 36 patients with soft tissue sarcoma with tail-like lesions treated with neoadjuvant therapy, including chemotherapy, radiotherapy, or both. The effect of neoadjuvant therapy on the tail sign was investigated by analyzing the change in tail-like lesions during neoadjuvant therapy and histological responses. The median length of the tail-like lesion reduced from 29.5 mm at initiation to 19.5 mm after neoadjuvant therapy. The extent of shrinkage in tail-like lesions was related to the histopathological responses in the main part of the tumor. Complete disappearance of the tail-like lesion was observed in 12 patients; however, it was not related to achieving a microscopically negative margin. The oncologic outcomes did not significantly differ between cases with and without the complete disappearance of tail-like lesions. This study indicated that the shrinkage of tail-like lesions did not have a significant effect on complete resection or improvements of clinical outcomes. A more comprehensive evaluation is needed to elaborate on the surgical strategy.

Purpose: Retroperitoneal sarcoma (RPS) is a rare tumor with a poor prognosis and is often undetected until it is significantly enlarged. While surgical resection remains the primary treatment, there is little research on its benefits, especially that concerning the reoperation of recurrent disease. This study investigated the impact of surgical procedures, especially reoperation of recurrent RPS, on prognosis., Methods: This retrospective study included 51 patients who underwent radical resection surgery (R0 status) for primary or recurrent RPS without distant metastasis. Patient outcomes and prognosis were defined in terms of the clinicopathologic factors and surgical techniques performed., Results: In all cases, the 5-year disease-free survival (DFS) rate was 28.2%, 5-year overall survival rate was 89.9%, and 5-year no residual liposarcoma rate was 54.3% after operation and re-reoperation. There was a statistically significant difference between the 5-year DFS rate and 5-year no residual liposarcoma rate due to frequent re-reoperation (p = 0.011). On univariate analysis of primary and recurrent lesions, the histological type and the number of organs involved were identified as statistically significant prognostic factors. Patients with well-differentiated liposarcomas had a statistically better prognosis than those with other cancer types (primary RPS, p = 0.028; recurrence, p = 0.024)., Conclusions: Aggressive and frequent resection of recurrent RPS with combined resection of adjacent organs contributes to long-term survival. The establishment of a surgical strategy for RPS will require a prospective study., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Cancer and osteoporosis have high incidence rates in older populations. However, the treatment of osteoporosis among cancer patients has not been adequately described. Our purpose was to clarify the current practice patterns of osteoporosis treatment among cancer patients in an academic cancer center, and to analyze the efficacy of treatment interventions. Patient records from April 2009 to March 2018 were retrospectively reviewed, and the study included a total of 316 cancer patients with osteoporosis. After patients' data extraction, the patients were divided into two groups, with (n = 144) or without treatment (n = 172), and compared the outcomes of these groups to evaluate the medication effect. The primary outcome was new radiographic fragility fractures during the study period. The related factors associated with fracture injuries and the rate of adverse events, such as osteonecrosis in the jaw and atypical femoral fractures, were analyzed. The rate of treatment intervention was 45.6% among the patient groups. Among patients in the study group, breast cancer patients (n = 107) were mostly treated (n = 79, 73.8%) with oral bisphosphonate. A significant difference in new fracture rate was observed between the two groups (treatment group, 30.6%; non-treatment group, 54.7%), and the risk of fracture was 42% lower in the treatment group (hazard ratio, 0.58; 95% confidence interval, 0.39-0.86; p<0.05). Previous chemotherapy, steroid use, and older age were significantly associated with increased rate of new fragility fractures. The adverse event rate was 3.5% (presented in five cases). Older cancer patients who receive chemotherapy or steroids are strongly recommended undergo bone quality assessment and appropriate osteoporosis treatment to improve their prognosis., Competing Interests: The authors have declared that no competing interests exist.

Background/aim: The Archer FusionPlex platform is widely used for comprehensive fusion-gene detection in cancer tissues. This platform separately displays results for strong-evidence and weak-evidence fusion candidates (WEFCs). Distinctive fusion patterns are frequently found in the weak-evidence category and information about the patterns is clinically essential., Patients and Methods: We describe the type and frequency of WEFCs observed using the FusionPlex Sarcoma Panel (S Panel) and the FusionPlex ALK, RET, and ROS1 ver2 Panel (ARR Panel)., Results: A total of 97 specimens were examined and 620 candidates were detected and categorized as WEFCs. A median of five WEFCs were detected per sample. In the S Panel group, there were 13 WEFCs with a frequency of more than 1%. In the ARR Panel group, a total of 16 WEFCs were detected with a frequency of more than 1%., Conclusion: Specific WEFCs were detected according to the panel selected., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The present study aimed to determine functional outcomes in patients undergoing deltoid muscle resection for soft tissue sarcoma., Methods: Between 2002 and 2014, 18 patients with soft tissue sarcoma of the shoulder who underwent wide resection including the deltoid muscle, and were followed up for more than 12 months, were retrospectively included in the study. In all, 11 patients were male and 7 were female. The median age was 59 years, median follow-up duration was 37 months. The extent of resection of deltoid muscle, with or without rotator cuff damage, reconstruction methods, adjuvant therapy, oncological outcomes, and the International Society of Limb Salvage (ISOLS) score as functional outcomes were analyzed., Results: Six patients underwent total resection, and twelve underwent partial resections of deltoid muscle. The rotator cuff was resected in four patients. Soft tissue reconstruction was performed in 17 patients using a pedicled latissimus dorsi muscle flap. Two local recurrences and three distant metastases occurred during follow-up. Median overall survival was 72 months. The mean ISOLS score was 25.0 points (±4.6points). Univariate analysis revealed that there was no significant difference in ISOLS score regarding the extent of deltoid muscle resection. Multivariate analysis identified only combined resection of the rotator cuff as a significant prognostic factor for poor functional outcomes (P < 0.001)., Conclusions: The extent of resection of the deltoid muscle might not affect the functional outcomes determined by ISOLS score. If the rotator cuff is resected concurrently, satisfactory functional outcomes might not be obtained., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The Toronto Extremity Salvage Score (TESS) is the most widely used patient-reported outcome measure for orthopaedic oncology patients. However, minimal clinically important differences (MCIDs) in the TESS have not been analyzed. The aim of this study was to define the MCIDs of TESS in patients with lower extremity sarcoma., Methods: A total of 85 patients were investigated to calculate the MCIDs for TESS. Three different methods were used: 1) distribution-based methods based on one-half of the standard deviation and standard error of measurement (SEM) at the baseline, 2) anchor-based and receiver operating characteristic (ROC) analysis, and 3) anchor-based using Akaike's Information Criterion (AIC) analysis., Results: The MCIDs at 6 months were 4.9-7.8 by distribution-based methods and 4.3-4.4 by anchor-based methods. The MCIDs at 12 months were 4.0-6.9 by distribution-based methods and 10.6-11.6 by anchor-based methods., Conclusions: We calculated MCID values for the TESS based on distribution- and anchor-based approaches. Our results seem reasonable since MCIDs calculated by the different approaches had similar values. This knowledge will enable clinicians to identify meaningful functional improvements in sarcoma patients., (Copyright © 2019. Published by Elsevier B.V.)

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., (Copyright © 2019 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

The efficacy and safety of eribulin in Japanese patients with advanced soft-tissue sarcomas (STS) have not been evaluated in a large-scale cohort study. Thus, we aimed to investigate the clinical outcome of 82 Japanese patients with STS receiving eribulin across multiple study centers retrospectively. Of 82 STS patients receiving eribulin treatment, 13 were treated for locally unresectable tumor, 46 for metastasis, and 23 for both. The primary endpoint of this study was to evaluate the efficacy of eribulin against STS. The median age was 60 years. Thirty-seven were diagnosed with L-sarcoma (leiomyosarcoma or liposarcoma) and 45 had non-L-sarcoma. The median progression-free survival (PFS) for all patients was 2.7 months, with 3.4 months in those with L-sarcoma and 2.2 months in those with non-L-sarcoma. Patients with L-sarcoma showed a better PFS than those with non-L-sarcoma. Overall, the median survival time was 11.1 months, and 12.3 months and 7.9 months in patients with L-sarcoma and non-L-sarcoma, respectively; however, there was no significant differences between the groups. The prognostic significance of PS = 0 and both existence of local and metastatic STS was evaluated by multivariate analysis. We also evaluated the overall survival (OS) in patients with undifferentiated pleomorphic sarcoma (UPS) and other non-L-sarcomas. Patients with UPS had better OS than those with the other non-L-sarcomas. In conclusion, there was a significant difference in PFS between patients with L-sarcoma and non-L-sarcoma following treatment with eribulin. The anti-tumor potential of eribulin was evident in patients with UPS.

Background: According to improved functional outcome and life expectancy in orthopaedic oncology patients, there has been a growing interest in not only oncologic and functional outcomes but also health-related quality of life (HRQOL), including body image, mental status, or social activities, after surgery. However, there has been a lack of disease-specific measures focusing on the ability of orthopaedic oncology patients to evaluate their HRQOL comprehensively. Therefore, our aims in the present study were 1) to develop a patient-oriented disease-specific outcome measure of HRQOL for musculoskeletal oncology patients (COMMON-LE), and 2) to examine the practical applicability, reliability and validity of the COMMON-LE for patients with musculoskeletal tumors in the lower extremity., Methods: The COMMON-LE was developed by expert committee of orthopaedic oncology and rehabilitation. A total of 101 patients were surveyed using the COMMON-LE, as well as the TESS, the MSTS score, and the SF-36, to assess their psychometric characteristics, including reliability, validity, and responsiveness., Results: The COMMON-LE showed no marked floor and ceiling effects. Test-retest reliability and internal consistency determined using the intraclass correlation coefficient (0.928) and Cronbach's alpha (0.948-0.968), respectively, were excellent. Each domain of the COMMON-LE (pain, ADL, socioemotional condition and general health) was well correlated with the scores of the standard measures (SF-36, TESS, MSTS score). Factor analysis and the AIC network showed the questionnaire items of the COMMON-LE were clearly separable into three clusters according to their content, corresponding to each domain of the questionnaire., Conclusions: We have successfully developed and validated a disease-specific measure, the COMMON-LE, to evaluate not only physical function, but also various aspects of HRQOL in patients with musculoskeletal tumors. The COMMON-LE has sufficient reliability and internal consistency, and good validity, and appears to be practically applicable to this group of patients., (Copyright © 2018 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Postoperative complications of thoracic wall resection include respiratory complications, skin necrosis and infection. The aim of the present study was to examine postoperative complications in patients who required combined thoracic wall resection during the surgical removal of a tumor. The present study included 68 patients; there were 50 patients with lung tumors and 18 patients with musculoskeletal tumors. The clinical factors associated with complications were compared between the two groups. Preoperative and postoperative pulmonary function tests were performed to examine the residual pulmonary function in 16 patients. Thoracic cage reconstruction was performed in 46 patients. Postoperative complications occurred in 30 (44.1%) patients, and one patient died from postoperative pneumonitis. Compared with the pulmonary function preoperative test results, the postoperative results revealed a decrease in the mean vital capacity percentage and an increase in the mean forced expiratory volume within 1 sec as a percent of the forced vital capacity. In patients with lung tumors, pneumonectomy can result in an increased rate of complications following thoracic wall resection. Residual pulmonary function is affected by impaired thoracic cage expansion and removal of the lung. However, the results of the present study demonstrated that these complications can be somewhat stabilized by thoracic wall reconstruction.

Background: Treatment for patients with locally recurrent soft tissue sarcomas after wide resection is challenging, and few studies have examined the results of treating these patients. In treatment of recurrent tumors, it has been reported that positive margins are correlated to local rerecurrence, but the relationship between surgical margin and survival remains controversial and risk factors for local recurrences after wide resection of soft tissue sarcomas are not well established. This study examined clinical outcomes and factors associated with survival and local rerecurrence in patients with local recurrence after initial surgical treatment who underwent another resection with a goal of negative margins., Questions/purposes: The purpose of this study was to determine (1) oncologic outcomes (survival rates and local rerecurrence-free rates) of surgical treatment for patients with local recurrence after wide resection; (2) whether factors associated with survival and local rerecurrence-free rates can be determined; and (3) the proportion of patients treated by amputation at final followup., Methods: Between 1992 and 2013, we treated 530 patients with soft tissue sarcoma without metastasis. Of those, 26 (5%) were lost before 3 years of followup but were not known to have died. Of the remainder, 59 have had a local recurrence. Of those with a local recurrence, 34 (58%) were treated with wide resection, whereas 25 (42%) were treated with nonsurgical treatment including chemotherapy and radiotherapy. During that period, our general indications for wide resection were patients (1) without distant metastasis; or (2) without distant lymph node metastasis, and contraindications were distant organ metastasis and/or distant lymph node metastasis. Of those treated with wide resection, 30 (88%) were available for followup. We conducted a retrospective analysis of these 30 patients with local recurrence (17 men, 13 women) who had previously undergone wide resection. Patient followup ranged from 1 to 12 years (median, 5 years). Survivorship (including overall survival and survival free from repeat recurrence) was ascertained by the Kaplan-Meier method. Factors associated with survival were evaluated by the log-rank test. Amputations were performed when limb-sparing surgery was deemed unsuitable because of extensive involvement of the limb by tumor, including invasion of multiple muscle compartments and neurovascular components. Survivorship free from amputation was ascertained by the Kaplan-Meier method., Results: Overall 5- and 10-year Kaplan-Meier survival rates after resection were 70% (95% confidence interval [CI], 50%-91%) and 44% (95% CI, 12%-76%), respectively, and 12 patients (40%) developed distant metastases after the second operation. Ten patients (33%) had additional local recurrences, and overall 5- and 10-year local rerecurrence-free rates were 66% (95% CI, 48%-85%) and 50% (95% CI, 18%-81%), respectively. A positive margin was associated with further recurrence (5-year local rerecurrence-free rates of positive margin: 20% [95% CI, 0%-52%], negative margin: 89% [95% CI, 74%-100%], p < 0.01) and with survival (5-year survival rates of positive margin: 36% [95% CI, 0%-75%], negative margin: 91% [95% CI, 74%-100%], p < 0.01). The survival rate was lower in patients with recurrence developing after 2 years (5-year survival rates of within 2 years: 46% [95% CI, 2%-90%], after 2 years: 83% [95% CI, 62%-100%], p = 0.01). The overall 5- and 10-year amputation-free rates were 86% (95% CI, 74%-99%) and 81% (95% CI, 67%-96%), respectively., Conclusions: A surgical procedure with negative margins appears to be important for reducing the likelihood of local recurrences and improving survival of patients with rerecurrence after wide resection of soft tissue sarcomas. Although these findings need to be confirmed in larger studies, it appears that when tumor recurrence is evident within 2 years from the primary surgery, it is associated with a poor prognosis. Local recurrence within 2 years after wide resection may also be an indicator of aggressive tumor biology., Level of Evidence: Level IV, therapeutic study.

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 < 0.001)., Conclusion: The recurrence rate of GCTB was still high after curettage, especially in Campanacci grade III, and improvements in the therapeutic strategy are needed in this cohort. There is a possibility that a sufficient dose of preoperative denosumab can reduce recurrence after curettage. Recently, we have started a clinical trial, JCOG1610, to investigate the efficacy of preoperative denosumab in patients who can be treated with curettage in GCTB.

Background: Biological reconstruction with recycled heat-treated autografts has been an option for a segmental skeletal defect after intercalary resection for malignant musculoskeletal tumors in the extremity. This study was undertaken to evaluate the clinical outcomes in patients treated with this procedure and identify factors affecting the incidence of complications., Methods: We retrospectively reviewed 24 patients treated with heat-treated autografts after intercalary resection at our institution between 1992 and 2015., Results: The survival rate of the heat-treated autografts was 70.1% at 10 years. Of the 48 host-graft junctions in the 24 patients, nonunion occurred in 18 junctions (38%). In the univariate analysis, location in the upper extremity, intercalary grafts without vascularized fibula autografts (VFG), and junction at the diaphysis significantly increased the rate of nonunion (P = 0.003, P = 0.003, and P = 0.031, respectively). Location in the upper extremity was an independent factor associated with nonunion in the multivariate analysis (P = 0.006). Upper extremity location and intercalary grafts without VFG were also significant factors for bone absorption (P = 0.042 and P < 0.001, respectively)., Conclusions: Our results can provide useful information to devise possibly novel clinical approaches to patients requiring intercalary reconstruction of the extremity., (© 2018 Wiley Periodicals, Inc.)