Controversies in orthopaedic oncology.

Chondrosarcoma is the second most common surgically treated primary bone sarcoma. Despite a large number of scientific papers in the literature, there is still significant controversy about diagnostics, treatment of the primary tumour, subtypes, and complications. Therefore, consensus on its day-to-day treatment decisions is needed. In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) attempted to gain global consensus from 300 delegates from over 50 countries. The meeting focused on these critical areas and aimed to generate consensus statements based on evidence amalgamation and expert opinion from diverse geographical regions. In parallel, periprosthetic joint infection (PJI) in oncological reconstructions poses unique challenges due to factors such as adjuvant treatments, large exposures, and the complexity of surgery. The meeting debated two-stage revisions, antibiotic prophylaxis, managing acute PJI in patients undergoing chemotherapy, and defining the best strategies for wound management and allograft reconstruction. The objectives of the meeting extended beyond resolving immediate controversies. It sought to foster global collaboration among specialists attending the meeting, and to encourage future research projects to address unsolved dilemmas. By highlighting areas of disagreement and promoting collaborative research endeavours, this initiative aims to enhance treatment standards and potentially improve outcomes for patients globally. This paper sets out some of the controversies and questions that were debated in the meeting.

Cerebrospinal Fluid Lysophosphatidylcholine Species for Distinguishing Narrowing of the Lumbar Spine.

BACKGROUND: Reoperation, sometimes multiple, is common with progressively worse outcomes in patients with degenerative lumbar spine diseases. Lysophosphatidylcholine (LPC), a precursor of lysophosphatidic acid, in the cerebrospinal fluid (CSF) is a possible biomarker for neuropathic pain and discriminating neuropathic pain caused by lumbar spinal canal stenosis (LSCS) from other etiologies. This study aimed to explore this possible use of LPC species in the CSF. METHODS: Patients with LSCS (n = 137) and persistent spinal pain syndrome (n = 22) were subjected in this multi-site observational study. The CSF was collected by lumbar puncture. Using liquid chromatography-tandem mass spectrometry, we measured 6 LPC species, (16:0), (18:0), (18:1), (18:2), (20:4), and (22:6), in the CSF. We compared the LPC values between the groups and determined the cutoff levels that could efficiently discriminate the groups with high accuracy. RESULTS: The levels of all measured LPC species were significantly higher in the LSCS group than the persistent spinal pain syndrome group. Four LPC species demonstrated more than 0.80 area under the curve obtained from the receiver operating characteristic curve analysis. Although the specificity of cutoff levels for the 6 LPC species was low to moderate, their sensitivity was consistently high. CONCLUSIONS: The existing diagnostic protocols combining physical examinations and morphological imaging studies for lumbar spinal pain have limited sensitivity. Measuring LPC species in the CSF is a promising objective laboratory test and could be suitable for detecting the presence of lumbar spinal stenosis and can help indications for surgery.

Factors predictive of second-line chemotherapy in soft tissue sarcoma: An analysis of the National Genomic Profiling Database.

Of the drugs used in second-line chemotherapy for soft tissue sarcoma (STS), trabectedin is effective for liposarcoma and leiomyosarcoma (L-sarcoma), eribulin for liposarcoma, and pazopanib for non-liposarcoma. The indications for these drugs in STS other than L-sarcoma have not been established. Here we explored the prognosis, mutation profiles, and drug-response factors in STS using real-world big data. Clinicogenomic data on 1761 patients with sarcoma who underwent FoundationOne CDx were obtained from a national database in Japan. Patients with TP53 and KDM2D mutations had a significantly shorter survival period of 253 (95% CI, 99-404) and 330 (95% CI, 20-552) days, respectively, than those without mutations. Non-supervised clustering based on mutation profiles generated 13 tumor clusters. The response rate (RR) to trabectedin was highest in an MDM2-amplification cluster (odds ratio [OR]: 2.2; p = 0.2). The RR was lowest for eribulin in an MDM2-amplification cluster (OR: 0.4; p = 0.03) and highest in a TERT-mutation cluster (OR: 3.0; p = 0.03). The RR was highest for pazopanib in a PIK3CA/PTEN-wild type cluster (OR: 2.1; p = 0.03). In particular, patients harboring mutations in genes regulating the PI3K/Akt/mTOR pathway had a lower RR than patients without mutations (OR: 0.3; p = 0.04). In STS, mutation profiles were more useful in predicting the drug response than histology. The present study demonstrated the potential of tailored therapy guided by mutation profiles established by comprehensive genomic profiling testing in optimizing second-line chemotherapy for STS. The findings of this study will hopefully contribute some valuable insights into enhancing STS treatment strategies and outcomes.

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

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

Hip Transposition Can Provide Early Walking Function After Periacetabular Tumor Resection: A Multicenter Study.

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.

Clinical Outcomes of Mirogabalin Treatment for Neuropathic Pain Due to Spinal Diseases in Patients Intolerant to Continuous Administration of Pregabalin.

Introduction: We often treat patients with peripheral neuropathic pain due to spine diseases with mirogabalin as an alternative to pregabalin because of adverse events or insufficient efficacy associated with pregabalin treatment. However, there have been few reports on the safety and efficacy of mirogabalin in such cases. This study aimed to evaluate the safety and efficacy of switching from pregabalin to mirogabalin in patients with peripheral neuropathic pain due to spine diseases. Methods: Between January 2019 and July 2021, we treated 106 patients (47 men and 59 women) with peripheral neuropathic pain due to spine diseases. All patients had switched from pregabalin to mirogabalin due to adverse events or lack of efficacy. We evaluated the retention rate, incidence of adverse events, and response rate of mirogabalin during the treatment course. Results: The mean age of the patients was 67.5 years (range, 33-93 years), and the average dose of mirogabalin was 13.8 mg (range, 2.5-30 mg) at the final follow-up. The average duration of mirogabalin treatment was 148.7 days (range, 3-463 days). The retention rate of mirogabalin was 78.3%, the incidence of adverse events after mirogabalin administration was 28.3%, and the response rate of mirogabalin was 66%. Somnolence with pregabalin or mirogabalin administration in the mirogabalin discontinuation group was increased compared with that in the mirogabalin continuation group (pregabalin: 52.2% vs. 19.3%, mirogabalin: 26.1% vs. 7.2%). The patients who responded to mirogabalin had a lower average age, higher retention rate, and longer drug administration period than those who did not respond to it. Conclusions: This study indicated that mirogabalin treatment might be continued in patients with peripheral neuropathic pain due to spinal diseases who could not continue pregabalin treatment.

Complications and Functional Outcome Differences in Carbon Ion Radiotherapy and Surgery for Malignant Bone Tumors of the Pelvis: A Multicenter, Cohort Study.

BACKGROUND: Carbon ion radiotherapy (CIRT) is an evolving treatment option for malignant pelvic tumors in patients with poor surgical indications. However, the difference in complications and functional outcomes between CIRT and surgery is poorly understood. This study compares the complications and functional outcomes of CIRT and surgery to facilitate treatment selection. METHODS: A total of 28 patients who underwent CIRT for pelvic bone tumors while theoretically meeting the surgical resection criteria were included. Sixty-nine patients who underwent surgery for pelvic bone tumors were included as controls. Major complication rates and functional outcomes (ambulatory, pain, urination, constipation) were evaluated and compared at several time points (pretreatment, discharge, and final follow-up) between the groups. RESULTS: Early (within 90 days) major complications were not observed in the CIRT group but occurred in 30% of the surgery group, which was statistically significant (P < 0.001). In contrast, late (after 90 days) major complications occurred more often in the CIRT group than in the surgery group (18% and 4%, respectively; P = 0.042). From pretreatment until discharge, all functional outcomes in the surgery group deteriorated (P < 0.001 for all) but did not change in the CIRT group (P = 0.77-1.00). At the final follow-up, all functional outcomes showed no significant intergroup difference (P = 0.28-0.92) due to the recovery trend in the surgery group and the deterioration trend in the CIRT group. CONCLUSIONS: Compared with surgery, CIRT may have favorable safety and stable functional outcomes in the short-term but more late complications. Mid-term functional outcomes were similar between the groups.

Selection bias due to delayed comprehensive genomic profiling in Japan.

Patients with advanced cancer undergo comprehensive genomic profiling in Japan only after treatment options have been exhausted. Patients with a very poor prognosis were not able to undergo profiling tests, resulting in a selection bias called length bias, which makes accurate survival analysis impossible. The actual impact of length bias on the overall survival of patients who have undergone profiling tests is unclear, yet appropriate methods for adjusting for length bias have not been developed. To assess the length bias in overall survival, we established a simulation-based model for length bias adjustment. This study utilized clinicogenomic data of 8813 patients with advanced cancer who underwent profiling tests at hospitals throughout Japan between June 2019 and April 2022. Length bias was estimated by the conditional Kendall τ statistics and was significantly positive for 13 of the 15 cancer subtypes, suggesting a worse prognosis for patients who underwent profiling tests in early timing. The median overall survival time in colorectal, breast, and pancreatic cancer from the initial survival-prolonging chemotherapy with adjustment for length bias was 937 (886-991), 1225 (1152-1368), and 585 (553-617) days, respectively (median; 95% credible interval). Adjusting for length bias made it possible to analyze the prognostic relevance of oncogenic mutations and treatments. In total, 12 tumor-specific oncogenic mutations correlating with poor survival were detected after adjustment. There was no difference in survival between FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) or gemcitabine with nab-paclitaxel-treated groups as first-line chemotherapy for pancreatic cancer. Adjusting for length bias is an essential part of utilizing real-world clinicogenomic data.

Dedifferentiated liposarcoma in the extremity and trunk wall: A multi-institutional study of 132 cases by the Japanese Musculoskeletal Oncology Group (JMOG).

BACKGROUND: Dedifferentiated liposarcoma occurs predominantly in the retroperitoneum. Given the paucity of cases, information on the clinical characteristics of this entity in the extremities and trunk wall is quite limited. In particular, the significance of preoperative evaluation and principles of intraoperative management of the different components, i.e., well-differentiated and dedifferentiated areas, are still to be defined. METHODS: Clinical characteristics, treatment outcomes, and risk factors for poor oncological outcomes in cases of dedifferentiated liposarcoma in the extremity or trunk wall were analyzed by a retrospective, multicentric study. RESULTS: A total of 132 patients were included. The mean duration from the initial presentation to dedifferentiation was 101 months in dedifferentiation-type cases. The 5-year local recurrence-free survival, metastasis-free survival, and disease-specific survival rates were 71.6%, 75.7%, and 84.7%, respectively. Among 32 patients with metastasis, 15 presented with extrapulmonary metastasis. A percentage of dedifferentiated area over 87.5%, marginal/intralesional margin, and R1/2 resection in the dedifferentiated area were independent risk factors for local recurrence. Dedifferentiated areas over 36 cm2, French Federation of Cancer Centers Sarcoma Group grade III, and intralesional or marginal resection were independent risk factors for metastasis. A dedifferentiated area over 77 cm2 and lung metastasis were independent risk factors for disease-specific mortality. CONCLUSIONS: The typical clinical characteristics of dedifferentiated liposarcoma in the extremity and trunk wall were reconfirmed in the largest cohort ever. The evaluation of the dedifferentiated area in terms of grade, extension, and pathological margin, together with securing adequate surgical margins, was critical in the management of this entity.

Dedifferentiation in low-grade osteosarcoma: a Japanese Musculoskeletal Oncology Group (JMOG) study.

BACKGROUND: Low-grade osteosarcomas, namely parosteal osteosarcoma (POS) and low-grade central osteosarcoma (LGCOS), occasionally dedifferentiate into high-grade malignancy, referred to as dedifferentiation in low-grade osteosarcoma (DLOS). This study aimed to elucidate the clinicopathologic features of DLOS, which are poorly described to date due to the extreme rarity of the disease. METHODS: A total of 33 patients with DLOS were included. Clinical characteristics, including the diagnostic accuracy of tumor biopsy, multimodal treatments, and clinical course, were retrospectively reviewed. Univariate analysis was performed to identify prognostic factors associated with overall survival (OS) and metastasis-free survival (MFS). RESULTS: The tumor subtypes comprised 10 cases (30.3%) of LGCOS and 23 cases (69.7%) of POS. The timing of dedifferentiation was synchronous in 25 (75.8%) and metachronous in 8 (24.2%) patients. The rates of preoperative diagnosis of DLOS were 40.0% and 65.4% for core needle biopsy and incisional biopsy, respectively. All patients underwent surgery and 25 patients received perioperative chemotherapy. Of the 13 patients who received neoadjuvant chemotherapy, 11 exhibited a poor histological response. The 5-year OS and MFS rates were 88.1% and 77.7%, respectively. Univariate analysis revealed that local recurrence was associated with poor OS (P < 0.01) and MFS (P < 0.01). Perioperative chemotherapy did not affect OS or MFS. CONCLUSIONS: The diagnostic accuracy of tumor biopsy for DLOS was lower than that for bone sarcomas, as reported previously. In contrast to conventional osteosarcomas with high chemosensitivity, both histological responses and survival analysis revealed low efficacy of chemotherapy for DLOS.

Japanese Orthopaedic Association (JOA) clinical practice guidelines on the management of soft tissue tumors 2020 - Secondary publication.

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.

Minimally invasive plate osteosynthesis with locking plate for metastatic humeral fractures.

BACKGROUND: Limited reports have examined the outcomes and complications of minimally invasive plate osteosynthesis (MIPO) with a locking plate (LP) in metastatic humeral fractures. Therefore, this study aimed to evaluate the effectiveness of MIPO in the treatment of metastatic humeral fractures. METHODS: Patients who underwent MIPO for metastatic humeral fractures were included in this study. Data on patient demographics, new Katagiri score, operative time, amount of blood loss, bone union rate, range of motion (ROM) of the shoulder and elbow, and perioperative complications were obtained. RESULTS: Twelve patients (seven men and five women) with 14 fractures were included in this study. The median operative time was 92.6 ± 28.9 min (range, 57-175 min) and the median amount of intraoperative blood loss was 106.1 ± 109.5 g (range, 10-330 g). No patient required surgery-related transfusion. The median duration of acquisition of active elbow ROM of>100° and active shoulder flexion of >90° were 8.9 ± 6.6 days (range, 1-30 days) and 17.5 ± 13.0 days (range, 6-47 days), respectively. The mean follow-up period was 10.0 ± 9.0 months (range, 1-33 months). There were no complications, and no patient required any further surgery for the affected humerus until death. CONCLUSION: MIPO using an LP provided acceptable functional outcomes in advanced-stage cancer patients with metastatic humeral fractures during their limited lifetime.

Systemic inflammation response index (SIRI) as a predictive factor for overall survival in advanced soft tissue sarcoma treated with eribulin.

BACKGROUND: Eribulin is a tubulin and microtubule-targeting drug that has clinical benefit in overall survival (OS) for patients with advanced soft tissue sarcoma. Eribulin's efficacy has been confirmed in several clinical trials, although no clinically useful biomarkers have been identified. We therefore sought to clarify the predictive factor of eribulin treatment, while focusing on systemic inflammation and immune response values. METHODS: This study included 33 advanced STS patients treated with eribulin between March 2016 and September 2019. We evaluated the associations of clinical factors influencing the efficacy of eribulin treatment and systemic inflammatory and immune response, including the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the lymphocyte-to-monocyte ratio (LMR), the systemic inflammation response index (SIRI), and the prognostic nutrition index (PNI), with progression-free survival (PFS) and OS using the Kaplan-Meier method and log-rank test. RESULTS: NLR, LMR, PLR, SIRI, and PNI were unassociated with PFS. Compared with patients with SIRI <1.5, those with an SIRI ≥1.5 had a significantly shorter OS [median OS 15 months (95% confidence interval [CI] 8-not reached) vs. 7 months (95% CI 3-14), P = 0.04]. Moreover, the PFS tended to be shorter for patients with SIRI ≥1.5 who received chemotherapy after eribulin treatment than in those with SIRI >1.5 [median PFS 92.5 days (95% CI 27-204) vs. 133 days (95% CI 36-507), P = 0.08]. CONCLUSIONS: High SIRI values may predict poorer overall survival and the efficacy of subsequent drugs after eribulin treatment among patients with advanced soft tissue sarcoma.

Effect of Early vs Delayed Surgical Treatment on Motor Recovery in Incomplete Cervical Spinal Cord Injury With Preexisting Cervical Stenosis: A Randomized Clinical Trial.

Importance: The optimal management for acute traumatic cervical spinal cord injury (SCI) is unknown. Objective: To determine whether early surgical decompression results in better motor recovery than delayed surgical treatment in patients with acute traumatic incomplete cervical SCI associated with preexisting canal stenosis but without bone injury. Design, Setting, and Participants: This multicenter randomized clinical trial was conducted in 43 tertiary referral centers in Japan from December 2011 through November 2019. Patients aged 20 to 79 years with motor-incomplete cervical SCI with preexisting canal stenosis (American Spinal Injury Association [ASIA] Impairment Scale C; without fracture or dislocation) were included. Data were analyzed from September to November 2020. Interventions: Patients were randomized to undergo surgical treatment within 24 hours after admission or delayed surgical treatment after at least 2 weeks of conservative treatment. Main Outcomes and Measures: The primary end points were improvement in the mean ASIA motor score, total score of the spinal cord independence measure, and the proportion of patients able to walk independently at 1 year after injury. Results: Among 72 randomized patients, 70 patients (mean [SD] age, 65.1 [9.4] years; age range, 41-79 years; 5 [7%] women and 65 [93%] men) were included in the full analysis population (37 patients assigned to early surgical treatment and 33 patients assigned to delayed surgical treatment). Of these, 56 patients (80%) had data available for at least 1 primary outcome at 1 year. There was no significant difference among primary end points for the early surgical treatment group compared with the delayed surgical treatment group (mean [SD] change in ASIA motor score, 53.7 [14.7] vs 48.5 [19.1]; difference, 5.2; 95% CI, -4.2 to 14.5; P = .27; mean [SD] SCIM total score, 77.9 [22.7] vs 71.3 [27.3]; P = .34; able to walk independently, 21 of 30 patients [70.0%] vs 16 of 26 patients [61.5%]; P = .51). A mixed-design analysis of variance revealed a significant difference in the mean change in ASIA motor scores between the groups (F1,49 = 4.80; P = .03). The early surgical treatment group, compared with the delayed surgical treatment group, had greater motor scores than the delayed surgical treatment group at 2 weeks (mean [SD] score, 34.2 [18.8] vs 18.9 [20.9]), 3 months (mean [SD] score, 49.1 [15.1] vs 37.2 [20.9]), and 6 months (mean [SD] score, 51.5 [13.9] vs 41.3 [23.4]) after injury. Adverse events were common in both groups (eg, worsening of paralysis, 6 patients vs 6 patients; death, 3 patients vs 3 patients). Conclusions and Relevance: These findings suggest that among patients with cervical SCI, early surgical treatment produced similar motor regain at 1 year after injury as delayed surgical treatment but showed accelerated recovery within the first 6 months. These exploratory results suggest that early surgical treatment leads to faster neurological recovery, which requires further validation. Trial Registration: ClinicalTrials.gov Identifier: NCT01485458; umin.ac.jp/ctr Identifier: UMIN000006780.

Soft tissue sarcoma in adolescent and young adult patients: a retrospective study using a nationwide bone and soft tissue tumor registry in Japan.

OBJECTIVE: The relationship between the adolescent and young adult age groups and poor overall survival in soft tissue sarcoma and the risk factors for poor outcomes in adolescent and young adult patients with soft tissue sarcoma were analyzed. METHODS: The medical records of 7759 Japanese patients diagnosed with soft tissue sarcoma from 2006-13 were accessed from the Bone and Soft Tissue Tumor registry. The epidemiological features of adolescent and young adult patients were compared with those of other age groups. The cancer survival rates were calculated using the Kaplan-Meier method. The prognostic factors for cancer survival were analyzed with the Cox proportional hazards models. The primary endpoint for prognosis was tumor-related death. RESULTS: There were 210 children, 1467 adolescent and young adults, 2771 adults and 3311 elderly among the 7759 patients identified with soft tissue sarcoma. Compared with other age groups, the proportions of myxoid/round cell liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor, primitive neuroectodermal tumor and rhabdomyosarcoma in adolescent and young adult patients were the highest, but none was significantly more prevalent in adolescent and young adult patients. On multivariate analysis, age was not a prognostic factor for poor cancer survival among adolescent and young adult patients with soft tissue sarcoma. The cancer survival rates of adolescent and young adult patients with malignant peripheral nerve sheath tumor were poorer than those of the other age groups; however, adolescent and young adult age was not a prognostic factor on multivariate analysis in malignant peripheral nerve sheath tumor patients. CONCLUSIONS: Our study is the first to investigate soft tissue sarcoma in adolescent and young adult patients using the nationwide Bone and Soft Tissue Tumor registry. Adolescent and young adult age is not a prognostic factor for poor cancer survival among those with soft tissue sarcoma in Japan.

Benefit of surgical resection of distant metastasis in soft tissue sarcoma: a systematic review.

OBJECTIVE: The aim of this systematic review was to evaluate the efficacy of metastasectomy for patients with advanced soft tissue sarcoma and to develop a recommendation outlining clinical guidelines for soft tissue sarcoma. METHODS: We searched the pertinent literature from January 1985 to December 2017. Two reviewers evaluated and screened the literature independently for eligibility and extracted data. We evaluated the quality of body of evidence and made a recommendation according to the Grading of Recommendations Development and Evaluation methodology. RESULTS: Among 244 identified studies, only 10 were finally included in this review and no randomized controlled trial reports were present. The median survival period after metastasectomy ranged from 9.6 to 39.6 months, and the 5-year survival rate ranged from 8 to 52%. The complication rate ranged from 7.3 to 25%, and the perioperative mortality rate was 0-1%. The guidelines committee proposed 'Metastasectomy can be offered for malignant soft tissue tumours with distant metastases'. This recommendation gained 100% consensus among the members of the guidelines group. CONCLUSIONS: Although the level of evidence is very low, many retrospective studies support a clinical advantage for metastasectomy, and surgical indications should be carefully considered for patients with metastasis from soft tissue sarcoma. Metastasectomy is an option for patients with metastasis and should be done only if it can be performed safely and if potential advantages outweigh disadvantages.

Prognostic factors and impact of surgery in patients with metastatic soft tissue sarcoma at diagnosis: A population-based cohort study.

BACKGROUND: Approximately 10% of the patients with soft tissue sarcoma show metastasis at initial diagnosis, and hence, poorer prognosis. However, the prognostic factors and whether definitive surgery for the primary lesion improves overall survival, especially when complete resection of metastasis is difficult, remain unclear. METHODS: This retrospective analysis was based on the Bone and Soft Tissue Tumor Registry in Japan. Patients with soft tissue sarcoma having metastasis at diagnosis were enrolled, excluding those with Ewing's sarcoma, rhabdomyosarcoma and several other sarcomas with unique behavior and treatment strategies. Overall survival was estimated using the Kaplan-Meier method and compared among the common histologic subtypes. Multivariate analysis with the Cox regression model was used to identify the prognostic factors. RESULTS: In total, 1184 patients were included, with a median follow-up duration of 10 months (range: 1-83). The median overall survival was 21 months (95% confidence interval: 18.2-23.8). The multivariate analyses indicated that tumor size, grade and histologic subtypes significantly correlated with overall survival. Moreover, surgery for the primary lesion, in addition to surgery for metastases and chemotherapy, showed significant association with better survival. CONCLUSIONS: The prognostic factors in patients with metastatic soft tissue sarcoma at diagnosis are generally similar to those in patients with localized disease. The overall survival in patients differed significantly according to histologic subtype. Surgical resection of primary lesions, especially those with a wide margin, may be an independent prognostic factor. Further studies are needed identify which subgroup of patients would benefit the most from primary lesion surgery.

Surgical margin for phosphaturic mesenchymal tumors in soft tissues: An analysis of the radiological histopathological correlation.

BACKGROUND: Phosphaturic mesenchymal tumors primarily cause tumor-induced osteomalacia, a rare paraneoplastic syndrome, and half occur in soft tissues. There are few reports about the surgical margins of these tumors. This study aimed to clarify the optimal surgical margin for phosphaturic mesenchymal tumors by analyzing radiological and histopathological features. METHODS: This study included eight cases, seven primary and one recurrent, of tumor-induced osteomalacia caused by soft-tissue phosphaturic mesenchymal tumors that were surgically treated between January 2000 and January 2019. We evaluated the radiological and histopathological features of all tumors and investigated the correlation of these features, the surgical margin, and recurrence of hypophosphatemia. RESULTS: The tumors were located in superficial (n = 5) and deep (n = 3) tissues. Six of the eight tumors had a clear boundary, but five had an irregular margin. Three tumors had a hypointense rim on T2-weighted images, indicating fibrous tumor encapsulation. Histopathological analysis revealed infiltrative growth in six of the eight tumors, which correlated with an irregular margin seen on imaging. Although there was no recurrence in patients treated with an intended wide margin >1 cm, one of the three patients treated with marginal tumor resection experienced a recurrence of hypophosphatemia, with histopathological analysis showing infiltration of subcutaneous fat. In contrast, two tumors with clear boundaries, regular margins, and fibrous capsule seen on imaging, had no infiltrative growth and were cured by marginal resection. In one recurrent case, tumor infiltration was observed in the previous surgical scar, which was not detected on preoperative imaging. CONCLUSIONS: Soft-tissue phosphaturic mesenchymal tumors with an irregular boundary seen on imaging tend to be infiltrative, especially into subcutaneous fat, and should be treated by at least a 1-cm wide margin resection. Tumors with a fibrous capsule with clear and regular margins are cured by marginal margin resection. These findings could inform surgeons' decisions regarding the resection of soft-tissue phosphaturic mesenchymal tumors.