Reoperation after surgery for bone metastasis of renal cell carcinoma.

BACKGROUND AND OBJECTIVE: The prognosis of metastatic renal cell carcinoma (RCC) has markedly improved with the advent of molecular targeted therapies and immune checkpoint inhibitors. However, the therapeutic response in patients with bone metastasis remains low; therefore, surgery still plays a significant role in treatment of bone metastasis. It is important to maintain quality of life for patients with bone metastasis from RCC and avoid reoperation after surgery for bone metastasis. Therefore, we investigated the risk factors for reoperation after surgery in patients with bone metastasis from RCC. METHODS: We retrospectively studied 103 bones of 97 patients who underwent surgery for bone metastasis of RCC from 2001 to 2023 at our institutions. RESULTS: Reoperation was performed in 10 (9.7%) of 103 bones. There was no correlation between reoperation-free survival and any of the following variables: preoperative and postoperative radiotherapy, site of bone metastasis, indication for surgery (solitary bone metastasis or impending or pathologic fractures), surgical method (intramedullary nailing fixation, curettage, or en bloc resection), preoperative embolization, or survival. CONCLUSION: The risk of reoperation for bone metastasis of RCC does not appear to be based on the surgical method.

What Is the Revision-free Survival of Resurfaced Allograft-prosthesis Composites for Proximal Humerus Reconstruction in Children With Bone Tumors?

BACKGROUND: Reconstruction of the proximal humerus in children who undergo bone tumor resection is challenging because of patients' small bone size and possible limb length discrepancy at the end of skeletal growth due to loss of the physis. There are several options for proximal humerus reconstruction in children, such as clavicula pro humero, free vascularized fibula grafting, massive bone osteoarticular allografting, endoprostheses, and allograft-prosthesis composites, but no consensus exists on the best method for reconstruction. Resurfaced allograft-prosthesis composites could be an alternative surgical option, but little is known about the results of this surgical technique. QUESTIONS/PURPOSES: (1) What are the complications and what is the survivorship free from reconstruction failure associated with resurfaced allograft-prosthesis composites in a small, single-center case series? (2) What Musculoskeletal Tumor Society scores do patients achieve after reconstructions with resurfaced allograft-prosthesis composites? METHODS: This study was a retrospective, single-arm case analysis in a single institution. We generally considered resurfaced allograft-prosthesis composites in children with malignant bone tumors involving the metaepiphysis of the proximal humerus in whom there was no evidence of joint contamination and in whom axillary nerve preservation was possible. Between 2003 and 2021, we treated 100 children (younger than 15 years) with bone tumors of the humerus. Thirty children (30%) with diaphyseal tumors (21 children) or distal tumors (9 children) were excluded. Among the potentially eligible children, 52 were not analyzed because they were treated with other procedures such as amputation, modular prostheses, cement spacers, free vascularized fibula grafting, and massive bone osteoarticular allografts. We included 18 children (26% of the potentially eligible children) who were treated with resurfaced allograft-prosthesis composites. There were 9 boys and 9 girls, with a median age of 10 years (range 4 to 15 years) at the time of diagnosis. A long stem (≥ 6 cm) in the resurfaced allograft-prosthesis composite was used in 9 children and a short stem (< 6 cm) was used in the remaining 9. One of the 18 children had a follow-up of less than 2 years. The median follow-up of the remaining 17 children was 4.7 years (range 2 to 19 years). The children' medical records were reviewed for clinical and functional outcomes. We performed a competing risk analysis to calculate the reconstruction failure-free survival of resurfaced allograft-prosthesis composites. Reconstruction failure was defined as removal of the implant or allograft because of implant loosening or breakage and allograft fracture or resorption. We analyzed the children's postoperative complications and functional outcomes at the end of the follow-up period using the Musculoskeletal Tumor Society functional scoring system. RESULTS: The competing risk analysis revealed that reconstruction failure was 25% (95% confidence interval 7% to 40%) at 3 years, reaching a plateau. Four of 18 children underwent surgical revision with a new reconstruction. The reasons for reconstruction revision were resorption of the allograft at the proximal part (2 children) and fracture of the allograft (2 children). Reconstruction revision was performed in 3 of 9 children who underwent reconstruction with a short stem and in 1 of 9 children who underwent reconstruction with a long stem. Several children had other complications that did not result in removal of the allograft. Allograft resorption was observed in 4 of 18 children, but no additional surgical treatment was performed. Shoulder instability or subluxation was observed in 4 of 18 children, but only 1 child underwent surgery with a reverse shoulder arthroplasty without removal of the resurfaced allograft-prosthesis composite. Limited elbow motion because of plate impingement was observed in 1 child who underwent surgical cutting of the protruding distal part of the plate. Incomplete radial nerve palsy after surgery occurred in 1 child, with spontaneous resolution after 2 months. Screw loosening occurred in 2 children who underwent surgery with removal of loose screws. Two children had a nonunion at the graft-host bone junction; 1 child underwent surgery with bone grafting and refixation of the graft-host bone junction, and the other child with both nonunion and plate breakage was treated with bone grafting and refixation of the graft-host bone junction with a new plate. Among 17 children who had a follow-up longer than 2 years, the median Musculoskeletal Tumor Society functional score at the last follow-up interval was 23 of 30 (range 20 to 26); 1 child was considered to have an excellent result (functional score ≥ 26), 15 children were considered to have a good result (functional score 21 to 25), and 1 child was considered to have a fair result (functional score ≤ 20). The Musculoskeletal Tumor Society functional score did not change after excluding 4 children who underwent replacement of resurfaced allograft-prosthesis composites (24 of 30 [range 20 to 26]). The median angle of flexion of the shoulder was 40° (range 20º to 90°), and the median angle of abduction was 30° (range 20º to 90°). CONCLUSION: Resurfaced allograft-prosthesis composites showed a high risk of complications, but not all complications resulted in removal of the reconstructed allograft. We used this technique mainly for very young children with small bones and for older children who underwent axillary nerve preservation. Although its success may be limited owing to a high risk of complications, a resurfaced allograft-prosthesis composite could be an alternative surgical option in order to preserve the bone stock and achieve good functional outcomes in very young children. We recommend using a long-stem resurfaced allograft-prosthesis composite, which may reduce the risk of complications. LEVEL OF EVIDENCE: Level IV, therapeutic study.

What Are the Complications, Reconstruction Survival, and Functional Outcomes of Modular Prosthesis and Allograft-prosthesis Composite for Proximal Femur Reconstruction in Children With Primary Bone Tumors?

BACKGROUND: Proximal femur reconstruction after bone tumor resection in children is a demanding surgery for orthopaedic oncologists because of the small bone size and possible limb-length discrepancy at the end of skeletal growth owing to physis loss. The most commonly used reconstruction types used for the proximal femur are modular prostheses and allograft-prosthesis composites. To our knowledge, there are no previous studies comparing the outcomes after modular prosthesis and allograft-prosthesis composite reconstruction of the proximal femur in children with primary bone tumors. QUESTIONS/PURPOSES: (1) What was the cumulative incidence of reoperation for any reason after allograft-prosthesis composite and modular prosthesis reconstructions of the proximal femur in children with primary bone tumors? (2) What was the cumulative incidence of reconstruction removal or revision arthroplasty in those two treatment groups? (3) What complications occurred in those two treatment groups that were managed without further surgery or with surgery without reconstruction removal? METHODS: Between 2000 and 2021, 54 children with primary bone tumors underwent resection and reconstruction of the proximal femur at a single institution. During that time, allograft-prosthesis composite reconstruction was used in very young children, in whom we prioritize bone stock preservation for future surgeries, and children with good response to chemotherapy, while modular prosthesis reconstruction was used in older children and children with metastatic disease at presentation and poor response to chemotherapy. We excluded three children in whom limb salvage was not possible and 11 children who underwent either reconstruction with free vascularized fibular graft and massive bone allograft (n = 3), an expandable prosthesis (n = 3), a massive bone allograft reconstruction (n = 2), a rotationplasty (n = 1), standard (nonmodular) prosthesis (n = 1), or revision of preexisting reconstruction (n = 1). Further, we excluded two children who were not treated surgically, three children with no medical or imaging records, and three children with no follow-up. All the remaining 32 children with reconstruction of the proximal femur (12 children treated with modular prosthesis and 20 children treated with allograft-prosthesis composite reconstruction) were accounted for at a minimum follow-up time of 2 years. Children in the allograft-prosthesis group were younger at the time of diagnosis than those in the modular prosthesis group (median 8 years [range 1 to 16 years] versus 15 years [range 9 to 17 years]; p = 0.001]), and the follow-up in the allograft-prosthesis composite group was longer (median 5 years [range 1 to 23 years] versus 3 years [range 1 to 15 years]; p = 0.37). Reconstruction with hemiarthroplasty was performed in 19 of 20 children in the allograft-prosthesis composite group and in 9 of 12 children in the modular prosthesis group. A bipolar head was used in 16 of 19 children, and a femoral ceramic head without acetabular cup was used in 3 of 19 children in the allograft-prosthesis composite reconstruction group. All 9 children in the modular prosthesis group were reconstructed with a bipolar hemiarthroplasty. Reconstruction with total arthroplasty was performed in one child in the allograft-prosthesis composite group and in three children in the modular prosthesis group. For both groups, we calculated the cumulative incidence of reoperation for any reason and the cumulative incidence of reconstruction removal or revision arthroplasty; we also reported qualitative descriptions of serious complications treated nonoperatively in both groups. RESULTS: The cumulative incidence of any reoperation at 10 years did not differ between the groups with the numbers available (36% [95% confidence interval 15% to 58%] in the allograft-prosthesis composite group versus 28% [95% CI 5% to 58%] in the modular proximal femoral replacement group). The cumulative incidence of reconstruction removal or revision arthroplasty at 10 years likewise did not differ between the groups with the numbers available (10% [95% CI 2% to 28%] versus 12% [95% CI 0% to 45%], respectively). In the allograft-prosthesis composite group (20 children), hip instability (n = 3), nonunion (n = 2), fracture of the greater trochanter (n = 1), screw loosening (n = 1), limb-length discrepancy (n = 1), and coxalgia due to acetabular wear (n = 1) were treated surgically without reconstruction removal. Complications treated without surgery included resorption of the allograft at the trochanteric region (n = 4), fracture of the greater trochanter (n = 4), limb-length discrepancy (n = 6), and coxalgia due to acetabular wear (n = 2). In the modular prosthesis group (12 children), hip instability (n = 1), coxalgia due to acetabular wear (n = 1), and limb-length discrepancy (n = 1) were treated surgically without reconstruction removal. Complications treated without surgery included hip instability (n = 2), stress shielding (n = 6), infection (n = 1), sciatic nerve palsy (n = 1), and limb-length discrepancy (n = 3). CONCLUSION: Although the two groups of children were not directly comparable due to differences in age and clinical characteristics, both modular prosthesis and allograft-prosthesis composite reconstructions of the proximal femur after bone tumor resection appear to be reasonable options with similar revision-free survival and complications. Therefore, the type of reconstruction following proximal resection in children with bone sarcoma should be chosen taking into consideration factors such as patient age, bone size, implant availability, technical expertise, and the surgeon's preference. Although children treated with expandable prostheses were not included in this study, such prostheses may be useful in bridging the surgical defect while correcting residual limb-length discrepancies even though they face limitations such as small intramedullary diameter, short residual bone segments, as well as stress shielding, loosening, and breakage. LEVEL OF EVIDENCE: Level III, therapeutic study.

Histological and imaging features of myoepithelial carcinoma of the bone and soft tissue.

OBJECTIVE: To depict histological and imaging features of myoepithelial carcinoma of the bone and soft tissue. MATERIALS AND METHODS: We retrospectively examined histological features in 22 patients with myoepithelial carcinoma of the bone (4 patients) and soft tissue (18 patients) at a single institution. Imaging analysis of 15 patients (bone, 3 patients; soft tissue, 12 patients;) with preoperative images involved classifying lytic bone lesions via the modified Lodwick-Madewell classification; the growth patterns of soft tissue lesions were classified as well-defined, focally invasive, or diffusely invasive. RESULTS: Local recurrence occurred in eight out of 22 patients (36.3%). Four of 22 patients (18.2%) had metastasis at presentation, whereas 11 of 22 patients (50.0%) had distant metastasis during follow-up. Severe cytological pleomorphism was observed in 14 of 22 patients (63.6%), and 10 of 22 tumors (45.5%) showed ≥ 10 mitoses/10 high-power fields. Vascular invasion was observed in 10 of 22 patients (45.5%). Extracapsular/extraskeletal infiltration into the surrounding tissues was assessed in 20 patients, with 14 of them (70%) showing infiltration beyond the tumor border. Regarding imaging of bone lesions, two patients had Ludwick type IIIB, whereas one patient had type II. The growth pattern of soft tissue lesions was well-defined in two patients (16.7%), focally invasive in seven patients (58.3%), and diffusely invasive in three (25.0%) out of 12 patients. CONCLUSION: Myoepithelial carcinoma of the bone and soft tissue presents high risk of local recurrence and distant metastasis. Histological and imaging features might be important to understand the aggressive behavior of the tumor.

A reduction in tumor volume exceeding 65% predicts a good histological response to neoadjuvant chemotherapy in patients with Ewing sarcoma.

OBJECTIVE: No consensus exists for tumor volume response criteria in patients with Ewing sarcoma. This study aimed to identify an optimal cutoff for predicting a good histological response by analyzing tumor volume changes and tumor necrosis after neoadjuvant chemotherapy. MATERIALS AND METHODS: We performed a retrospective analysis of 184 Ewing sarcoma patients, analyzing tumor volume changes before and after neoadjuvant chemotherapy. Patients were divided into two groups based on histological response: good (tumor necrosis ≥ 95%) and poor (tumor necrosis < 95%) responders. The receiver operating characteristic (ROC) area under the curve (AUC) method was used to determine the optimal thresholds for predicting the histological response. Additionally, the prognostic value of this cutoff for relapse-free survival was assessed. RESULTS: Out of 184 patients, 83 (45%) had tumor necrosis ≥ 95%, while 101 (55%) had tumor necrosis < 95%. ROC analysis identified the optimal cutoff for a good histological response as over 65% tumor volume reduction (AUC = 0.69; p < 0.001). Patients with volume reduction of ≥ 65% had a higher likelihood of a good histological response than those with lesser reductions (p = 0.004; odds ratio = 2.61). Multivariable analysis indicated a correlation between poor histological response and reduced relapse-free survival (hazard ratio = 2.17; p = 0.01), while tumor volume reduction itself did not impact survival. CONCLUSION: We reported that a tumor volume reduction of ≥ 65% was able to predict a good histological response in Ewing sarcoma patients. We recommend preoperative tumor volume assessment to identify patients at greater risk for poor histological response who could benefit from more intensive chemotherapy protocols or additional radiotherapy.

Malawer type I/V proximal humerus reconstruction after tumor resection: a systematic review.

BACKGROUND: Several reconstruction methods exist for Malawer type I/V proximal humerus reconstruction after bone tumor resection; however, no consensus has been reached regarding the preferred methods. METHODS: We conducted a literature search on various types of proximal humerus oncologic reconstruction methods. We collected data on postoperative functional outcomes assessed based on Musculoskeletal Tumor Society (MSTS) scores, 5-year reconstruction survival rates, and complications. We calculated each reconstruction's weighted mean based on the sample size and standard errors. Complications were categorized based on the Henderson classification. Based on these integrated data, our primary objective is to propose an optimal strategy for proximal humerus reconstruction after bone tumor resection. RESULTS: We examined various reconstruction techniques, including modular prosthesis (752 patients in 21 articles), osteoarticular allograft (142 patients in 6 articles), allograft prosthesis composites (APCs) (236 patients in 12 articles), reverse shoulder total arthroplasty (141 patients in 10 articles), composite reverse shoulder total arthroplasty (33 patients in 4 articles), claviculo-pro-humero (CPH) technique (51 patients in 6 articles), and cement spacer (207 patients in 4 articles). Weighted mean MSTS scores were: modular prosthesis (73.8%), osteoarticular allograft (74.4%), APCs (79.2%), reverse shoulder total arthroplasty (77.0%), composite reverse shoulder total arthroplasty (76.1%), CPH technique (75.1%), and cement spacer (69.1%). Weighted 5-year reconstruction survival rates were modular prosthesis (85.4%), osteoarticular allograft (67.6%), APCs (85.2%), reverse shoulder total arthroplasty (84.1%), and cement spacer (88.0%). Reconstruction survival data was unavailable for composite reverse shoulder total arthroplasty and CPH technique. Major complications included shoulder joint instability: modular prosthesis (26.2%), osteoarticular allograft (41.5%), APCs (33.9%), reverse shoulder total arthroplasty (17%), composite reverse shoulder total arthroplasty (6.1%), CPH technique (2.0%), and cement spacer (8.7%). Aseptic loosening of the prosthesis occurred: modular prosthesis (3.9%) and reverse shoulder total arthroplasty (5.7%). Allograft fracture was observed in 54.9% of patients with osteoarticular allograft. CONCLUSION: The complication profiles differed among reconstruction methods. Weighted mean MSTS scores exceeded 70% in all methods except cement spacer, and the 5-year reconstruction survival rate surpassed 80% for all methods except osteoarticular allograft. Proximal humerus reconstruction after bone tumor resection should consider potential complications and patients' individual factors.

Dimensional assessment on baseline MRI of soft-tissue sarcomas: longest diameter, sum and product of diameters, and volume-which is the best measurement method to predict patients' outcomes?

PURPOSE: The longest diameter (LD) is a strong prognostic factor for patients with soft-tissue sarcoma (STS). Other dimensional assessments, such as the sum of diameters (SoD), product of diameters (PoD), and volume (3D-COG - proposed by the Children Oncology Group), can be rapidly performed; however, their prognostic values have never been compared to LD. Our goal was to investigate their performance in improving patients' prognostication for STS of the lower limbs. METHODS: All consecutive adults managed with curative intent at our sarcoma reference center for a newly diagnosed STS of the lower limbs between 2000 and 2017, with pre-treatment MRI, were included in this retrospective study. Multivariable Cox regression models were trained to predict metastasis-free survival (MFS) in a Training cohort of 66.7% patients based on LD, PoD, SoD, or 3D-COG (and systematically including age, histologic grade, histotype, radiotherapy, chemotherapy, and surgical margins as covariables). The models were then compared on a validation cohort of 33.3% patients using concordance indices (c-index). The same approach was applied for overall survival (OS) and local relapse-free survival (LFS). Measurement reproducibility among three readers was evaluated with an intraclass correlation coefficient (ICC). RESULTS: 382 patients were included in the survival modeling (72/253 [28.5%] metastatic relapses in Training and 36/129 [27.9%] metastatic relapses in Validation). Higher dimensions were associated with lower MFS (multivariable hazard ratio [HR] = 2.44 and P = 0.0018 for LD; HR = 1.88 and P = 0.0009 for PoD, HR = 1.52 and P = 0.0041 for SoD; and HR = 1.08 and P = 0.0195 for 3D-COG). Higher c-indices were obtained with PoD model in Training (c-index = 0.772) and Validation (c-index = 0.688), but they were not significantly higher than those obtained with LD model. None of the measurements was associated with LFS or OS. All measurements demonstrated excellent ICC (> 0.95). CONCLUSION: Regarding its simplicity and good performance, LD appeared as the best metric to incorporate in prognostic models and nomograms for MFS.

Similar complications, implant survival, and function following modular prosthesis and allograft-prosthesis composite reconstructions of the proximal femur for primary bone tumors: a systematic review and meta-analysis.

PURPOSE: There is a lack of consensus regarding the best type of reconstruction of the proximal femur following bone tumor resection. The objective of this study was to analyze the complication risks, implant survival, and functional outcomes following modular prosthesis (MP) and allograft-prosthesis composite (APC) reconstruction of the proximal femur after primary bone tumor resections. METHODS: We performed a search in the PubMed and Scopus libraries, obtaining 1 843 studies. We included studies reporting functional outcomes, complications, and implant survival of proximal femur reconstruction with MP or APC following primary bone tumor resection with a 2-year minimum follow-up. We excluded studies analyzing metastatic patients or studies with pooled data in which it was impossible to separate the data of patients with primary bone tumors from those with bone metastases. RESULTS: We analyzed 18 studies (483 patients) reporting on 234 (48%) patients with MP reconstruction and 249 (52%) patients with APC reconstruction. The risk of complications was similar in patients with MP reconstruction (29%; 95% CI [0.11; 0.47]) and APC reconstruction (36%; 95% CI [0.24; 0.47]) (p = 0.48). Implant survival following MP reconstruction ranged from 81 to 86% at 5 years, 75 to 86% at 10 years, and 82% at 15 years. Implant survival following APC reconstruction ranged from 86 to 100% at 5 years and 86% at 10 years, and 86% at 15 years. Functional outcomes following MP reconstruction and APC reconstruction ranged from 24.0 to 28.3 and from 21.9 to 27.8, respectively. CONCLUSION: Patients with primary bone tumor of the proximal femur who underwent MP or APC reconstruction seem to have similar complication risks, implant survival, and functional outcomes.

Risk of complications and implant survival of surgical treatment of proximal femoral metastasis: a meta-analysis.

PURPOSE: The patients with femoral metastasis in the inter- or subtrochanteric area could be treated with intramedullary nailing or prosthetic reconstruction, however, it is controversial which surgical treatment could offer less complications and implant failure. Our purpose was to define the risk of complications and implant survival in patients treated with intramedullary nailing or prosthetic reconstruction. METHODS: We analyzed studies reporting the risk of complications, reoperations and removal of the implant in patients treated with intramedullary nailing, hemiarthroplasty, arthroplasty or megaprosthesis. RESULTS: We analyzed 27 studies (1346 patients) reporting patients treated with intramedullary nail (51%), hemiarthroplasty (15%), arthroplasty (2%), megaprosthesis with (25%) or without (7%) acetabular component. No difference was found in the overall risk of complications between patients treated with intramedullary nailing 6%, hemiarthroplasty or total hip arthroplasty 7% and megaprosthesis 11% (p = 0.23). However, patients treated with megaprosthesis had increased risk of reoperation due to infection (70%), compared to the patients treated with intramedullary nail (13%), and patients treated with hemiarthroplasty or total hip arthroplasty (23%) (p = 0.02). Revision due to disease progression was required in 61% of the patients treated with intramedullary nail, but not in patients treated with hemiarthroplasty, total arthroplasty, and megaprosthesis (p = 0.03). CONCLUSION: Patients treated with megaprosthesis had higher risk of reoperation due to infection, while patients treated with intramedullary nailing had higher risk of revision due to disease progression. Regarding patients treated with megaprosthesis, the risk of reoperation due to dislocation was higher in those treated with acetabular component.

Outcome of rare primary malignant bone sarcoma treated with multimodal therapy: Results from the EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.).

BACKGROUND: Rare primary malignant bone sarcomas (RPMBS) account for 5%-10% of primary high-grade bone tumors and represent a major treatment challenge. The outcome of patients with RPMBS enrolled in the EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S) is presented. METHODS: Inclusion criteria were as follows: age from 41 to 65 years and a diagnosis of high-grade spindle cell, pleomorphic, or vascular RPMBS. The chemotherapy regimen included doxorubicin 60 mg/m2 , ifosfamide 9 g/m2 , and cisplatin 90 mg/m2 ; postoperative methotrexate 8 g/m2 was added in case of a poor histologic response. Version 2.0 of the Common Terminology Criteria for Adverse Events, Kaplan-Meier curves, log-rank tests, and univariate Cox regression models were used. RESULTS: In total, 113 patients were evaluable for analysis. The median patient age was 52 years (range, 40-66 years), and 67 patients were men. Eighty-eight tumors were categorized as undifferentiated pleomorphic sarcomas (UPS), 20 were categorized as leiomyosarcomas, three were categorized as fibrosarcomas, and two were categorized as angiosarcomas. Eighty-three of 113 tumors were located in the extremities. Ninety-five of 113 patients presented with no evidence of metastases. After a median follow-up of 6.8 years (interquartile range [IQR], 3.5-9.8 years), the 5-year overall survival rate for patients with localized disease was 68.4% (IQR, 56.9%-77.5%), and it was 71.7% (IQR, 58.1%-81.6%) for patients with UPS and 54.9% (IQR, 29.5%-74.5%) for patients with leiomyosarcoma. Grade III-IV hematologic toxicity was reported in 81% patients; 23% had grade II-III neurotoxicity, and 37.5% had grade I-II nephrotoxicity. Five-year overall survival was significantly better for patients with localized disease, for patients who obtained surgical complete remission, and when the primary tumor was located in the extremities. CONCLUSIONS: The survival of patients who had RPMBS in the current series was similar to that of age-matched patients who had high-grade osteosarcoma treated according to the same protocol. An osteosarcoma-like chemotherapy may be proposed in patients who have RPMBS.

Focused Ultrasound and External Beam Radiation Therapy for Painful Bone Metastases: A Phase II Clinical Trial.

Background Recent consensus statements and clinical trials have assessed the value of MRI-guided focused ultrasound surgery for pain palliation of bone metastases; however, a comparison with external beam radiation therapy (EBRT) has not been performed. Purpose To compare safety and effectiveness data of MRI-guided focused ultrasound and EBRT in the treatment of bone metastases. Materials and Methods Participants with painful bone metastases, excluding skull and vertebral bodies, were enrolled in a prospective open-label nonrandomized phase II study between January 2017 and May 2019 and underwent either MRI-guided focused ultrasound or EBRT. The primary end point was the overall response rate at 1-month following treatment, assessed via the numeric rating scale (NRS) for pain (0-10 scale, with zero meaning "no pain" and 10 meaning "the worst pain imaginable"). Secondary end points were improvements at 12-month follow-up in NRS and quality of life (QoL) measures, including the Brief Pain Inventory (BPI), QoL-Questionnaire Cancer-15 Palliative Care (QLQ-C15-PAL), and QoL-Questionnaire Bone Metastases-22 (QLQ-BM22) and analysis of adverse events. Statistical analyses, including linear regression, χ2 test, and Student t test followed the per-protocol principle. Results Among 198 participants, 100 underwent MRI-guided focused ultrasound (mean age, 63 years ± 13 [SD]; 51 women), and 98 underwent EBRT (mean age, 65 years ± 14; 52 women). The overall response rates at 1-month follow-up were 91% (91 of 100) and 67% (66 of 98), respectively, in the focused ultrasound and EBRT arms (P < .001), and complete response rates were 43% (43 of 100) and 16% (16 of 98) (P < .001). The mean baseline NRS score was 7.0 ± 2.1 for focused ultrasound and 6.6 ± 2.4 for EBRT (P = .16); at 1-month follow-up, they were reduced to 3.2 ± 0.3 and 5.1 ± 0.3 (P < .001), respectively. QLQ-C15-PAL for physical function (P = .002), appetite (P < .001), nausea and vomiting (P < .001), dyspnea (P < .001), and QoL (P < .001) scores were lower in the focused ultrasound group. The overall adverse event rates were 15% (15 of 100) after focused ultrasound and 24% (24 of 98) after EBRT. Conclusion MRI-guided focused ultrasound surgery and external beam radiation therapy showed similar improvements in pain palliation and quality of life, with low adverse event rates. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Kelekis in this issue.

Fusion transcriptome profiling defines the monoclonal origin of multifocal epithelioid haemangioma of bone.

AIMS: Epithelioid haemangioma (EH) of bone remains a highly controversial entity. Indeed, the WHO classifies EHs of soft tissues as benign tumours, whereas bone EHs are considered intermediate-locally aggressive tumours due to common multifocal presentation and local destructive growth. To gain insights into the clinical behaviour and biology of EH of bone we retrospectively analysed 42 patients treated in a single institution from 1978 to 2021. METHODS AND RESULTS: Multifocal presentation was detected in 17 of 42 patients (40%) primarily as synchronous lesions. Patients were treated with curettage (57%), resection (29%) or biopsy, followed by radiotherapy or embolisation (14%). Follow-up (minimum 24 months) was available for 38 patients, with only five local recurrences (13%) and no death of disease. To clarify whether the synchronous bone lesions in multifocal EH represent multicentric disease or clonal dissemination, four cases were profiled by RNA-sequencing. Separate lesions from the same patient, which showed a similar transcriptional profile, expressed the same fusion transcript (involving FOS or FOSB) with identical gene breakpoints. CONCLUSIONS: These results indicate that, in EH of bone, multifocal lesions are clonally related and therefore represent the spread of a same neoplastic clone rather than simultaneous independent tumours. This finding is in apparent contradiction with the benign clinical course of the disease, and suggests that tumour dissemination in bone EH probably reflects a phenomenon of passive spreading, with tumour cells colonising distal sites while maintaining their benign biological nature.

Is the association of electrochemotherapy and bone fixation rational in patients with bone metastasis?

BACKGROUND: Bone metastases are frequent in patients with cancer. Electrochemotherapy (ECT) is a minimally invasive treatment based on a high-voltage electric pulse combined with an anticancer drug. Preclinical and clinical studies supported the use of ECT in patients with metastatic bone disease, demonstrating that it does not damage the mineral structure of the bone and its regenerative capacity, and that is feasible and efficient for the treatment of bone metastases. Year 2014 saw the start of a registry of patients with bone metastases treated with ECT, whose data are recorded in a shared database. QUESTIONS/PURPOSES: (1) Among patients who underwent ECT and internal fixation for bone metastasis, how many experienced a reduction of pain? (2) How many cases showed a radiological response? (3) How many patients presented local or systemic complication after ECT and fixation? PATIENTS AND METHODS: Patients were treated in Bologna at Rizzoli Orthopaedic Institute between March 2014 and February 2022 and recorded in the REINBONE registry (a shared database protected by security passwords): clinical and radiological information, ECT session, adverse events, response, quality of life indicators, and duration of follow-up were registered. We consider only cases treated with ECT and intramedullary nail during the same surgical session. Patients included in the analysis were 32: 15 males and 17 females, mean age 65 ± 13 years (median 66, range 38-88 years), mean time since diagnosis of primary tumor 6.2 ± 7.0 years (median 2.9, range 0-22 years). Nail was indicated in 13 cases for a pathological fracture in, 19 for an impending fracture. Follow-up was available for 29 patients, as 2 patients were lost to follow-up and 1 was unable to return to controls. Mean follow-up time was 7.7 ± 6.5 months (median 5, range 1-24), and 16 patients (50%) had a follow-up longer than 6 months. RESULTS: A significant decrease in pain intensity was observed at the mean Visual Numeric Scale after treatment. Bone recovery was observed in 13 patients. The other 16 patients remained without changes, and one presented disease progression. One patient presented a fracture occurrence during the ECT procedure. Among all patients, bone recovery was observed in 13 patients: complete recovery in 1 patient (3%) and partial recovery in 12 patients (41%). The other 16 patients remained without changes, and one presented disease progression. One patient presented a fracture occurrence during the ECT procedure. However, healing was possible with normal fracture callus quality and healing time. No other local or systemic complications were observed. CONCLUSION: We found that pain levels decreased after treatment in 23 of the 29 cases for a pain relief rate of 79% at final follow-up. Pain is one of the most important indicators of quality of life in patients that undergo palliative treatments. Even if conventional external body radiotherapy is considered a noninvasive treatment, it presents a dose-dependent toxicity. ECT provides a chemical necrosis preserving osteogenic activity and structural integrity of bone trabeculae; this is a crucial difference with other local treatments and allows bone healing in case of pathological fracture. The risk of local progression in our patient population was small, and 44% experienced bone recovery while 53% of the cases remained unchanged. We observe intraoperative fracture in one case. This technique, in selected patients, improves outcome in bone metastatic patients combing both the efficacy of the ECT in the local control of the disease and the mechanical stability with the bone fixation to synergize their benefits. Moreover, the risk of complication is very low. Although encouraging data, comparative studies are required to quantify the real efficacy of the technique. Level of Evidence Level I, therapeutic study.

Giant cell tumor of bone with secondary aneurysmal bone cyst does not have a higher risk of local recurrence.

BACKGROUND: Fluid-fluid levels (FFLs) is found in 10%-16% of giant cell tumor of bone (GCTB), and the presence of FFLs raises the suspicion of GCTB with secondary aneurysmal bone cyst (ABC), which can lead to increased intraoperative bleeding and, blurring the operative field, be associated with a risk of local recurrence. The first objective of this study is to determine whether secondary ABC is associated with a higher risk of local recurrence after curettage in patients with GCTB of the extremities. The second objective of this study is to investigate the sensitivity, specificity, positive predictive value, and negative predictive value of the presence of FFLs detected on magnetic resonance imaging (MRI) to diagnose secondary ABC associated with GCTB. METHODS: Two hundred and eighty patients with GCTB of the extremities who underwent curettage at the authors' institutions between 1980 and 2021 were included in this study. RESULTS: Secondary ABC was found in 36 of 280 patients (12.9%) and local recurrence occurred in 66 of 280 patients (23.6%). Multivariate analysis showed no significant correlation between secondary ABC and local recurrence (hazard ratio [HR]: 1.87 (95% confidence interval [CI]: 1.00-3.53]; p = 0.051). Preoperative MRI revealed FFLs in 13 of 82 patients (15.9%). Sensitivity, specificity, positive predictive value, and negative predictive value of FFLs detected on preoperative MRI to diagnose secondary ABC were 36.8%, 90.5%, 53.8%, and 82.6%, respectively. CONCLUSION: The results of this study showed that secondary ABC does not increase the risk of local recurrence after curettage in patients with GCTB of the extremities. Although rare, FFLs were present in patients with GCTB and half of those with FFLs detected on preoperative MRI had secondary ABC.

A prognostic score from a multicentric retrospective analysis of patients affected by sarcoma with metachronous lung metastases undergoing metastasectomy.

BACKGROUND: Despite the lack of evidence-based on prospective randomized studies, surgery has become the cornerstone of the treatment in patients with pulmonary oligometastatic sarcomas. Our study aimed to construct a composite prognostic score for metachronous oligometastatic sarcoma patients. METHODS: A retrospective analysis was performed on data patients who underwent radical surgery for metachronous metastases in six research institutes from January 2010 to December 2018. The log-hazard ratio (HR) obtained from the Cox model was used to derive weighting factors for a continuous prognostic index designed to identify differential outcome risks. RESULTS: A total of 251 patients were enrolled in the study. In the multivariate analysis, a longer disease-free interval (DFI) and a lower neutrophil-to-lymphocytes ratio (NLR) were predictive of a better overall survival (OS) and disease-free survival (DFS). A prognostic score was developed based on DFI and NLR data, identifying 2 risk class groups for DFS (3-years DFS 20.2% for the high-risk group [HRG]and 46.4% for the low-risk group [LRG] [<0.0001]) and 3 risk groups for OS (3 years OS 53.9% for the HRG vs. 76.9% for the intermediate-risk group and 100% of the LRG (p < 0.0001)). CONCLUSION: The proposed prognostic score effectively predicts outcomes for patients with lung metachronous oligo-metastases from the surgically treated sarcoma.

Outcome of re-operation for local recurrence following pre-operative denosumab administration and curettage for giant cell tumour of bone with difficult joint preservation.

PURPOSE: Denosumab enables joint-sparing surgery (curettage) and surgical downstaging in patients with giant cell tumour of bone (GCTB), where joint preservation is not possible. However, denosumab treatment causes osteosclerosis of the lesion, making it difficult to curet the lesion, leaving the tumour behind, and increasing the local recurrence rate. We performed a three-centre retrospective study to investigate the postoperative local re-recurrence rate, joint preservation status, and functional outcomes of locally recurrent lesions after preoperative denosumab treatment and curettage in patients with difficult joint preservation. METHODS: We included 38 of 142 patients with primary GCTB of the extremities who underwent preoperative denosumab and curettage between 2009 and 2021 with local recurrence. Preoperative denosumab was indicated in patients with minimal residual periarticular and subchondral bones, large extraosseous lesions (Campanacci stage 3), and pathological fractures that made joint preservation difficult. RESULTS: Local re-recurrence occurred in 6 (15.8%) of the 38 patients. In 29 patients who underwent re-curettage, local re-recurrence occurred in six patients (20.7%); however, in nine patients who underwent en bloc resection, no local re-recurrence was observed. The joint preservation rate was 63.2% (24 of 38 patients), with a median Musculoskeletal Tumor Society score of 28 (interquartile range: 26.8-29.0). The median follow-up period after surgery for local recurrence was 63.5 months (interquartile range: 42.5-82.4). CONCLUSION: Since the local re-recurrence rate after re-curettage for local recurrence was low, and the joint preservation rate and affected limb function were good, preoperative denosumab administration may be considered in patients who require downstaging to maintain good limb function (joint preservation).

Neoadjuvant chemotherapy in high-risk soft tissue sarcomas: A Sarculator-based risk stratification analysis of the ISG-STS 1001 randomized trial.

BACKGROUND: The value of neoadjuvant chemotherapy in soft tissue sarcoma (STS) is not completely understood. This study investigated the benefit of neoadjuvant chemotherapy according to prognostic stratification based on the Sarculator nomogram for STS. METHODS: This study analyzed data from ISG-STS 1001, a randomized study that tested 3 cycles of neoadjuvant anthracycline plus ifosfamide (AI) or histology-tailored (HT) chemotherapy in adult patients with STS. The 10-year predicted overall survival (pr-OS) was estimated with the Sarculator and was stratified into higher (10-year pr-OS < 60%) and lower risk subgroups (10-year pr-OS ≥ 60%). RESULTS: The median pr-OS was 0.63 (interquartile range [IQR], 0.51-0.72) for the entire study population, 0.62 (IQR, 0.51-0.70) for the AI arm, and 0.64 (IQR, 0.51-0.73) for the HT arm. Three- and 5-year overall survival (OS) were 0.86 (95% confidence interval [CI], 0.82-0.93) and 0.81 (95% CI, 0.71-0.86) in lower risk patients and 0.69 (95% CI, 0.70-0.85) and 0.59 (95% CI, 0.51-0.72) in the higher risk patients (log-rank test, P = .004). In higher risk patients, the 3- and 5-year Sarculator-predicted and study-observed OS rates were 0.68 and 0.58, respectively, and 0.85 and 0.66, respectively, in the AI arm (P = .04); the corresponding figures in the HT arm were 0.69 and 0.60, respectively, and 0.69 and 0.55, respectively (P > .99). In lower risk patients, the 3- and 5-year Sarculator-predicted and study-observed OS rates were 0.85 and 0.80, respectively, and 0.89 and 0.82, respectively, in the AI arm (P = .507); the corresponding figures in the HT arm were 0.87 and 0.81, respectively, and 0.86 and 0.74, respectively (P = .105). CONCLUSIONS: High-risk patients treated with AI performed better than predicted, and this adds to the evidence for the efficacy of neoadjuvant AI in STS. LAY SUMMARY: People affected by soft tissue sarcomas of the extremities and trunk wall are at some risk of developing metastasis after surgery. Preoperative or postoperative chemotherapy has been tested in clinical trials to reduce the chances of distant metastasis. However, study findings have not been conclusive. This study stratified the risk of metastasis for people affected by sarcomas who were included in a clinical trial testing neoadjuvant chemotherapy. Exploiting the prognostic nomogram Sarculator, it found a benefit for chemotherapy when the predicted risk, based on patient and tumor characteristics, was high.

Risk factors of fracture following curettage for bone giant cell tumors of the extremities.

BACKGROUND: Following curettage of giant cell tumor of bone (GCTB), it is common to fill the cavity with polymethylmethacrylate (PMMA) bone cement, bone allograft, or artificial bone to maintain bone strength; however, there is a 2-14% risk of postoperative fractures. We conducted this retrospective study to clarify the risk factors for fractures after curettage for GCTB of the extremities. METHODS: This study included 284 patients with GCTBs of the extremities who underwent curettage at our institutions between 1980 and 2018 after excluding patients whose cavities were not filled with anything or who had additional plate fixation. The tumor cavity was filled with PMMA bone cement alone (n = 124), PMMA bone cement and bone allograft (n = 81), bone allograft alone (n = 63), or hydroxyapatite graft alone (n = 16). RESULTS: Fractures after curettage occurred in 10 (3.5%) patients, and the median time from the curettage to fracture was 3.5 months (interquartile range [IQR], 1.8-8.3 months). The median postoperative follow-up period was 86.5 months (IQR, 50.3-118.8 months). On univariate analysis, patients who had GCTB of the proximal or distal femur (1-year fracture-free survival, 92.5%; 95% confidence interval [CI]: 85.8-96.2) presented a higher risk for postoperative fracture than those who had GCTB at another site (100%; p = 0.0005). Patients with a pathological fracture at presentation (1-year fracture-free survival, 88.2%; 95% CI: 63.2-97.0) presented a higher risk for postoperative fracture than those without a pathological fracture at presentation (97.8%; 95% CI: 95.1-99.0; p = 0.048). Patients who received bone grafting (1-year fracture-free survival, 99.4%; 95% CI: 95.7-99.9) had a lower risk of postoperative fracture than those who did not receive bone grafting (94.4%; 95% CI: 88.7-97.3; p = 0.003). CONCLUSIONS: For GCTBs of the femur, especially those with pathological fracture at presentation, bone grafting after curettage is recommended to reduce the risk of postoperative fracture. Additional plate fixation should be considered when curettage and cement filling without bone grafting are performed in patients with GCTB of the femur. This should be specially performed for those patients with a pathological fracture at presentation.

Surgical treatment scenario for osteoblastoma of the pelvis: Long-term follow-up results.

BACKGROUND: The aim of this study was to evaluate the results of different treatments for pelvic Osteoblastoma (OB). METHODS: We retrospectively evaluated 34 patients affected by primary pelvic OB from 3 oncologic referral centers. Patients with a minimum follow-up of 24 months were included. Local recurrence (LR) rate and complications were recorded. RESULTS: The primary treatment was radio-frequency ablation (RFA) in 4 patients (11.8%), curettage (ILC) in 21 (61.7%) and resection (EBR) in 9 (26.5%). Mean follow-up was 8.9 years (SD ± 6.6). Local recurrence free survival (LRFS) rate after primary surgery was 79.4% at 3 and 5 years. In details, LRFS rate at 3 and 5 years was 50.0% in RFA, 81.0% in ILC and 88.9% in EBR. Post-operative complications occurred in 6/34 patients (17.7%), in particular after EBR. CONCLUSIONS: RFA is the least invasive technique to treat OB but with high LR rate. Thus, it should be reserved to very small lesions. ILC is a suitable treatment for stage II OB. For stage III OB, EBR is the treatment of choice, despite an increased risk of complications. For selected stage III OB (relatively small, periacetabular area) ILC might be considered.

Intercalary reconstruction of the distal femur with or without physeal preservation: results and impact on limb growth.

PURPOSE: Allograft reconstruction with or without vascularized fibula can be a valuable solution to treat childhood intercalary tumours of the distal femur. We aimed to assess the oncological status, complication rate and survival of distal femur intercalary reconstruction after trans-metaphyseal (TMR) and trans-epiphyseal resection (TER). We also evaluated the impact of distal temporary graft fixation on skeletal growth after TMR. METHODS: We retrospectively reviewed 23 skeletally immature patients affected by distal femur osteosarcoma (18) and Ewing sarcoma (5). Mean patients age was 10.3 years. In 11 cases, TMR was performed with physis preservation and temporary distal graft fixation. In 9 patients, TER was performed with growth plate sacrifice. The last 3 cases were treated with TMR and sliding plate fixation. RESULTS: Mean follow-up was 8.4 years. No deaths occurred, but 3 patients presented lung metastasis and 2 cases presented local recurrence in soft tissues. 10 implant-related complications occurred, all surgically treated. At skeletal maturity, mean femoral dysmetria was 2.3 cm after TMR and temporary epiphysiodesis, and 3.1 cm after TER. In TMR group, a strong trend towards physeal recovery was observed after epiphyseal screws removal (p = 0.061), but valgus deformity in distal femur was more frequent (p = 0.049). MSTS score was good or excellent in all patients, with no statistically significant difference between TMR and TER. CONCLUSIONS: Intercalary graft reconstruction after TMR and TER allows good local disease control and excellent functional results with long-term follow-up. Temporary distal fixation might reduce the final limb discrepancy after TMR, but valgus deformity could develop. LEVEL OF EVIDENCE: Level IV.