Incidence and management of secondary deformities after megaendoprosthetic proximal femur replacement in skeletally immature bone sarcoma patients.

INTRODUCTION: Megaendoprosthetic reconstruction of bone defects in skeletally immature patients has led to the development of unique complications and secondary deformities not observed in adult patient cohorts. With an increasing number of megaendoprosthetic replacements performed, orthopedic oncologists still gain experience in the incidence and type of secondary deformities caused. In this study, we report the incidence, probable cause and management outcome of two secondary deformities after megaendoprosthetic reconstruction of the proximal femur: hip dysplasia and genu valgum. MATERIALS AND METHODS: Retrospective analysis of 14 patients who underwent primary and/or repeat reconstruction/surgery with a megaendoprosthetic proximal femur replacement between 2018 and 2022. RESULTS: Mean patient age was 9.1 years (range 4-17 years). Stress shielding was observed in 71.4%. Hip dislocation was the most frequent complication (50%). While four dislocations occurred without an underlying deformity, secondary hip dysplasia was identified in 58.3% (n = 7/12) of intraarticular resections and reconstructions, leading to dislocation in 71.4% (n = 5/7). A genu valgum deformity was observed in 41.6% (n = 5/12). The incidence of secondary hip dysplasia and concomitant genu valgum was 42.9% (n = 3/7). Triple pelvic osteotomy led to rebound hip dysplasia in two cases (patients aged < 10 years), whereas acetabular socket replacement led to stable hip joints over the course of follow-up. Temporary hemiepiphyseodesis was applied to address secondary genu valgum. CONCLUSIONS: Patients aged < 10 years were prone to develop secondary hip dysplasia and genu valgum following proximal femur replacement in this study. Management of secondary deformities should depend on remaining skeletal growth. Stress shielding was observed in almost all skeletally immature patients.

Slipped capital femoral epiphysis after tumor prosthesis implantation in a patient receiving chemotherapy.

While the usual etiology of slipped capital femoral epiphysis (SCFE) is idiopathic, there are many other factors that increase the predisposition to slippage. Chemotherapy can be one of them. In this article, we report a rare case of acute SCFE after tumor prosthesis implantation in a patient who received chemotherapy. A 10-year-old girl with osteosarcoma of the right distal femur underwent (neo-) adjuvant chemotherapy, wide tumor resection, and reconstruction using a growing tumor prosthesis and a short non-cemented femoral stem. Half a year after implantation, she developed aseptic loosening. Revision surgery was performed using a hydroxyapatite (HA)-coated cementless femoral stem. Postoperative plain radiographs revealed SCFE that was treated by closed reduction and screw fixation. The patient recovered without complications, and unaffected hip showed no radiographic signs of slippage on follow-up. The forces of implanting a tumor prosthesis, particularly with a non-cemented stem, can increase the risk of an acute SCFE. The controversy over prophylactic pinning of the uninvolved hip in chemotherapy-associated SCFE is unresolved. Pinning can be considered only in the presence of abnormal prodromal radiological findings.

Technical considerations for isolated limb perfusion: A consensus paper.

BACKGROUND: Isolated limb perfusion (ILP) is a well-established surgical procedure for the administration of high dose chemotherapy to a limb for the treatment of advanced extremity malignancy. Although the technique of ILP was first described over 60 years ago, ILP is utilised in relatively few specialist centres, co-located with tertiary or quaternary cancer centres. The combination of high dose cytotoxic chemotherapy and the cytokine tumour necrosis factor alpha (TNFα), mandates leakage monitoring to prevent potentially serious systemic toxicity. Since the procedure is performed at relatively few specialist centres, an ILP working group was formed with the aim of producing technical consensus guidelines for the procedure to streamline practice and to provide guidance for new centres commencing the technique. METHODS: Between October 2021 and October 2023 a series of face to face online and hybrid meetings were held in which a modified Delphi process was used to develop a unified consensus document. After each meeting the document was modified and recirculated and then rediscussed at subsequent meeting until a greater than 90% consensus was achieved in all recommendations. RESULTS: The completed consensus document comprised 23 topics in which greater than 90% consensus was achieved, with 83% of recommendations having 100% consensus across all members of the working group. The consensus recommendations covered all areas of the surgical procedure including pre-operative assessment, drug dosing and administration, perfusion parameters, hyperthermia, leakage monitoring and theatre logistics, practical surgical strategies and also post-operative care, response evaluation and staff training. CONCLUSION: We present the first joint expert-based consensus statement with respect to the technical aspects of ILP that can serve as a reference point for both existing and new centres in providing ILP.

Variation in response rates to isolated limb perfusion in different soft-tissue tumour subtypes: an international multi-centre study.

OBJECTIVE: The aim of this study was to investigate the response rates of different extremity soft-tissue sarcoma subtypes (eSTS) after isolated limb perfusion (ILP), based on an international multi-centre study. MATERIALS AND METHODS: The retrospective cohort comprised eSTS patients from 17 specialised ILP centres that underwent melphalan-based ILP, with or without recombinant human tumour necrosis factor (rhTNFα) (TM-ILP and M-ILP, respectively). Response was measured on imaging (magnetic resonance imaging) and/or clinical response, for which M-ILPs were excluded. RESULTS: A total of 1109 eSTS patients were included. The three most common histological subtypes were undifferentiated pleomorphic sarcoma (17%, n = 184), synovial sarcoma (16%, n = 175) and myxofibrosarcoma (8%, n = 87). rhTNFα was used in 93% (TM-ILP) and resulted in a significantly better overall response rate (ORR, p = 0.031) and complete responses (CR, p < 0.001) in comparison to M-ILP, without significant differences among histological subgroups. The ORR of TM-ILP was 68%, including 17% CR. Also, 80% showed progressive disease. Significantly higher response rates were shown for Kaposi sarcoma (KS) with 42% CR and 96% ORR (both p < 0.001), and significantly higher CR rates for angiosarcoma (AS, 45%, p < 0.001) and clear cell sarcoma (CCS, 31%, p = 0.049). ILP was followed by resection ≤ 6 months in 80% of the patients. The overall limb salvage rate was 88%, without significant differences among histological subgroups, but was significantly higher for ILP responders compared to non-responders (93% versus 76%, p < 0.001). CONCLUSION: ILP resulted in high response and LRS among all eSTS subtypes, however, with significant differences between subtypes with most promising results for KS, AS and CCS.

Outcome of Surgery as Part of Palliative Care of Patients with Symptomatic Advanced or Metastatic Extra-Abdominal High-Grade Soft Tissue Sarcoma.

Background: The modern multimodal treatment of malignant tumors has increased disease-specific survival and decreased the burden of tumor-associated complications. The main focus of palliative surgery is not based primarily on quantitative success parameters of tumor response but is instead mainly on the question of quality of life. Aim: The current study was conducted to analyze the clinical and oncological outcomes of palliative patients with soft tissue sarcoma. Design: Of 309 patients with extra-abdominal high-grade soft tissue sarcoma treated between August 2012 and December 2014, our retrospective analysis revealed 33 palliative patients for this study. All patients were evaluated and managed by a multidisciplinary team with expertise and experience in sarcoma treatment. The survival analysis was made using the Kaplan-Meier method. Results: The main sarcoma symptoms were pain (27.3%) and ulcerated tumors or shortly before ulceration (24.2%). Thirteen patients (39.4%) were operated on with negative margins, 15 (45.5%) with positive margins, 2 with tumor debulking (6.1%), and 3 patients (9.1%) were treated only with palliative hyperthermic isolated limb perfusion. Ten pedicle flaps were performed after sarcoma resection. The median operation time was 85 minutes (range, 37-216 minutes). The median hospitalization stay was 9.5 days (range, 3-27 days). No patients died during hospitalization. Twelve-month disease-free survival was 48.5% (95% confidence interval: 45.4-51.6). Conclusions: Palliative surgery of metastatic or advanced soft tissue sarcoma can improve the wound care and quality of life. Closed noninfected wounds enable further treatment options, such as chemotherapy, immunotherapy, and radiotherapy. This surgery should be considered during the discussion on interdisciplinary tumor boards.

Return to Sports and Activity in Tumor Orthopaedics. / Wiederkehr zu körperlicher Aktivität und Sport in der Tumororthopädie.

As survival rates associated with the multimodal treatment of malignant bone cancer (osteosarcoma and Ewing's sarcoma) are satisfactory, health-related quality of life and the return to activity and sports by the affected patients have attracted increasing attention in recent years. Nowadays, limbs can be salvaged for most patients using modular endoprostheses. Such patients are typically adolescents and young adults who have high activity levels and thereby high demands for multimodal cancer treatment. This study aimed to evaluate the activity levels and sporting proficiencies that can be attained after modular endoprosthetic treatment of bone sarcomas as well as the extent to which physiotherapeutic and sports interventions influence functional outcome and activity levels.This non-systematic review of the literature focused on the return to activity and sports after modular endoprosthetic treatment of lower extremities bone sarcomas in adolescents and young adults. The electronic database PubMed was screened for relevant publications on this issue. A treatment algorithm for return to activity and sports in tumor orthopaedics is proposed.The objective activity level (gait cycles per day and gait intensities) in patients treated for bone sarcomas is reduced in short- and long-term follow-ups compared with healthy controls and patients with other cancers (leukaemia). Although a negative impact is observed in terms of motor performance, it shows improvement over time. Functional assessment at 12 postoperative months is sensible as neoadjuvant chemotherapy is completed by then. In long-term follow-up, patients with bone sarcomas can achieve high sports activity levels, i.e., type of sport, frequency/week and UCLA score, after modular endoprosthetic reconstruction. The maximum level is attained at 5 years postoperatively. Nevertheless, there is a shift from high- and intermediate- to low-impact sports. Only 20% of the patients participate in school sports regularly without limitations. The localisation of bone sarcoma, but not the rate of postoperative complications, influences the postoperative activity level. Individualised sports-related interventions during and after multimodal treatment can improve the short-term activity levels; moreover, "serious games" can improve motor performance and postural control. There is no evidence that intense activity levels leads to early loosening of the endoprosthesis. There is insufficient valid data on activity and sports after modular endoprosthetic treatment of bone sarcomas of the upper extremities.High preoperative activity levels of young patients with bone sarcomas must be considered in tumour orthopaedics. Limitations on sports activities have a significant negative impact on the quality of life and mental health of such patients. Therefore, tumour orthopaedic treatment has to focus on preserving an improvement in these factors. The overall existing evidence concerning this issue is weak. Additional studies to evaluate the ability to return to specific sports activities are desirable, as well as prospective interventional studies.

Classic Type of Epithelioid Sarcoma of the Distal Upper Extremity: Clinical and Oncological Characteristics.

BACKGROUND: The classic type of epithelioid sarcoma (ES) is a rare, aggressive soft tissue neoplasm that most commonly affects the distal upper extremities of young patients. This study aimed to assess clinical features and provide a long-term report of the oncological outcome. METHODS: We retrospectively analyzed our clinical database for patients with ES of the distal upper extremities. RESULTS: Twenty-three patients with ES of the distal upper extremity were treated surgically between January 1990 and August 2018. ES affected most commonly the palmar side of young patients. The most common site affected by a sarcoma was the wrist in 47.8% of cases, followed by metacarpals and fingers with 34.8% and 17.4%, respectively. Most of the patients were treated according to the protocols of interdisciplinary tumor boards with multimodal therapy. A local recurrence was observed in 7 patients (30.4%). The 5 - and 10-year recurrence-free survival was 80.4% (95% confidence interval [CI]: 68.6-76.8) and 60.9% (95% CI: 53.5-68.3), respectively. The 5- and 10-years disease-specific survival was 89.9% (95% CI: 87-92.8) and 61.9% (95% CI: 56.5-67.3), respectively. Five patients (21.7%) had metastasis in regional lymph nodes. CONCLUSION: The classic type of ES represents a group of high-grade sarcomas, which affect the dominantly distal upper extremity. Specific clinical, diagnostic, and oncological characteristics make it difficult to diagnose and therapy. Wide tumor resection as a part of multimodal therapy remains a more viable and common treatment option for patients with ES on distal extremities. High rates of lymph node metastasis are typical for ES.

Optimization of the preoperative requirements of blood units for the surgical treatment of extra-abdominal soft tissue sarcoma: the TRANSAR score.

BACKGROUND AND OBJECTIVES: Excessive preoperative blood orders frequently occur during the preoperative planning of resections of sarcomas. We aimed to develop a prediction score model that would be able to identify a patient cohort in which the cross-matching could be safely evaded. PATIENTS AND METHODS: We retrospectively analyzed data of 309 consecutive patients with extra-abdominal soft tissue sarcomas treated between September 2012 and December 2014. Scorecard scores for variables were calculated and summarized to a total score that can be used for risk stratification. The score was used in a logistic regression model. Results of the optimized model were described as a receiver operating characteristic curve. RESULTS: Preoperative units of red blood cells were requested for 206 (66.7%) patients, of which only 31 (10%) received them. Five parameters were identified with high predictive power. In the visualized barplot, there was an increased risk of blood transfusion with a higher score of TRANSAR. CONCLUSION: A TRANSAR score is a new tool that can predict the probability of transfusion for patients with sarcoma. This may reduce the number of preoperative cross-matching and blood product ordering and associated costs without compromising patient care.

Pathological Fractures in Benign Bone Lesions - Diagnosis and Therapy. / Die pathologische Fraktur bei benignen Knochenläsionen - Diagnostik und Therapie.

INTRODUCTION: Most tumour-related pathological fractures occur in patients with bone metastases. However, in mostly younger patients, a pathological fracture can be due to both a benign or a malignant bone tumour. Making the correct diagnosis from among these two differential diagnoses is enormously important. If the tumour is malignant, treating the fracture inevitably leads to tumour cell contamination and can significantly worsen the oncological situation. The aim of this review article is firstly to provide the reader with diagnostic assistance in the case of suspected pathological fractures, and secondly to focus on the treatment of pathological fractures occurring with benign bone tumours. METHODS: This is a non-systematic review of the diagnosis and treatment of pathological fractures in benign bone tumours or tumour-like lesions, based on an electronic PubMed database search. We also present our own procedures, in particular for ruling out a malignant bone tumour. RESULTS AND DISCUSSION: Whenever a fracture occurs in the absence of sufficient traumatic force, the possibility of a pathological fracture should always be considered. As well as taking a general history for a possible primary tumour, it is particularly important to ask the patient whether they had any pain before the fracture occurred. If the findings from clinical examination or conventional radiological imaging give rise to suspicion of a pathological fracture, an MRI of the affected skeletal section with contrast medium should be carried out before commencing any fracture treatment. A CT scan is also helpful for accurately assessing bone destruction. If a malignant or locally aggressive benign bone tumour such as giant cell tumour (GCT) or aneurysmal bone cyst (ABC) cannot be definitively ruled out through imaging, a biopsy is essential. The bone biopsy must always be carried out on the assumption that the histological work-up will reveal a malignant bone tumour; it must therefore be performed according to strict oncological criteria. If the radiological diagnosis is unambiguous, e. g., a juvenile bone cyst (JBC) or a non-ossifying fibroma (NOF), conservative treatment of the fracture can be considered, depending on the location. In the presence of a locally aggressive benign bone tumour such as a GCT or ABC, curettage of the tumour must be carried out as well as treating the fracture. With GCT in particular, neoadjuvant therapy with denosumab prior to curettage and osteosynthesis or en bloc resection of the tumour should be considered, depending on the extent of the tumour. CONCLUSION: Pathological fractures, especially in younger patients, should not be overlooked. Only after a malignant or benign locally aggressive bone tumour has been definitively ruled out should fracture treatment be performed. In the presence of a locally aggressive bone tumour, as well as treating the fracture, it is usually necessary to perform curettage of the tumour - also en bloc resection, where applicable, in the case of a GCT. Depending on the location, benign, non-aggressive tumours can be treated conservatively if necessary.

"The Baltic Sea Germ": A Case Report of Necrotizing Fasciitis following Vibrio vulnificus Infection.

Reported is an 80-year-old patient with septic shock from necrotizing fasciitis secondary to a Vibrio vulnificus (Vv) infection. The patient reports having been swimming in the Baltic Sea after a minor trauma to the left leg. Emergency superficial necrosectomy followed by intensive medical therapy was performed. Antibiotic therapy was initiated with a third-generation cephalosporin and a tetracycline. Vv was detected in the intraoperative microbiological smears. Instead of a leg amputation and a flap, due to the patient's age, a split skin covering to consolidate the wound was performed. Vv is a gram-negative rod bacterium of the genus Vibrio. Vv occurs in warm, low-salinity seawater (brackish water). In Germany, Vv occurs primarily in river mouths of the low-salinity Baltic Sea. Infections by Vv can occur through open wounds or by eating raw infected seafood, especially oysters. Infection via wounds often take a fulminant lethal course. Patients with chronic diseases, weakened immune system, and open wounds are particularly at risk. Infections with Vv are rare, but occur worldwide. Global warming is expected to spread Vv as water temperature increases and the dilution effect of sea level rise further decreases ocean salinity, and natural disasters promote the spread of Vv.

68Ga-FAPI as a Diagnostic Tool in Sarcoma: Data from the 68Ga-FAPI PET Prospective Observational Trial.

Bone and soft-tissue sarcomas express fibroblast activation protein (FAP) on tumor cells and associated fibroblasts. Therefore, FAP is a promising therapeutic and diagnostic target. Novel radiolabeled FAP inhibitors (e.g., 68Ga-FAPI-46) have shown high tumor uptake on PET in sarcoma patients. Here, we report the endpoints of the 68Ga-FAPI PET prospective observational trial. Methods: Forty-seven patients with bone or soft-tissue sarcomas undergoing clinical 68Ga-FAPI PET were eligible for enrollment into the 68Ga-FAPI PET observational trial. Of these patients, 43 also underwent 18F-FDG PET. The primary study endpoint was the association between 68Ga-FAPI PET uptake intensity and histopathologic FAP expression analyzed with Spearman r correlation. Secondary endpoints were detection rate, positive predictive value (PPV), interreader reproducibility, and change in management. Datasets were interpreted by 2 masked readers. Results: The primary endpoint was met, and the association between 68Ga-FAPI PET uptake intensity and histopathologic FAP expression was significant (Spearman r = 0.43; P = 0.03). By histopathologic validation, PPV was 1.00 (95% CI, 0.87-1.00) on a per-patient and 0.97 (95% CI, 0.84-1.00) on a per-region basis. In cases with histopathologic validation, 27 of 28 (96%) confirmed patients and 32 of 34 (94%) confirmed regions were PET-positive, resulting in an SE of 0.96 (95% CI, 0.82-1.00) on a per-patient and 0.94 (95% CI, 0.80-0.99) on a per-region basis. The detection rate on a per-patient basis in 68Ga-FAPI and 18F-FDG PET was 76.6% and 81.4%, respectively. In 8 (18.6%) patients, 68Ga-FAPI PET resulted in an upstaging compared with 18F-FDG PET. 68Ga-FAPI PET readers showed substantial to almost perfect agreement for the defined regions (Fleiss κ: primary κ = 0.78, local nodal κ = 0.54, distant nodal κ = 0.91, lung κ = 0.86, bone κ = 0.69, and other κ = 0.65). Clinical management changed in 13 (30%) patients after 68Ga-FAPI PET. Conclusion: We confirm an association between tumoral 68Ga-FAPI PET uptake intensity and histopathologic FAP expression in sarcoma patients. Further, with masked readings and independent histopathologic validation, 68Ga-FAPI PET had a high PPV and sensitivity for sarcoma staging.

Localized Angiosarcoma, Not One Disease: A Retrospective Single-Center Study on Prognosis Depending on the Primary Site and Etiology.

BACKGROUND: Angiosarcomas are rare and heterogeneous tumors with poor prognosis. The clinical subtypes are classified depending on the primary site and etiology. METHODS: We conducted a retrospective, monocentric study of 136 patients with localized AS between May 1985 and November 2018. Overall survival (OS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS) were estimated using the Kaplan-Meier method. To identify prognostic factors, univariate and multivariate analyses were performed based on Cox regressions. RESULTS: The median age was 67 years (19-72.8 years). Primary sites were cutaneous (27.2%), breast (38.2%), and deep soft tissue (34.6%). The majority was primary angiosarcomas (55.9%) followed by postradiation (40.4%) and chronic lymphedema angiosarcomas (2.9%). Prognosis significantly differed depending on the primary site and etiology. Shortest median OS and MFS were observed in deep soft tissue angiosarcomas, whereas cutaneous angiosarcomas, angiosarcomas of the breast, and radiation-associated angiosarcomas displayed worse median LRFS. Univariate analyses showed better OS for tumor size <10 cm (p = 0.009), negative surgical margins (p = 0.021), and negative lymph node status (p = 0.007). LRFS and MFS were longer for tumor size <10 cm (p = 0.012 and p = 0.013). In multivariate analyses, age <70 years was the only independent positive prognostic factor for OS in all subgroups. For LRFS, secondary AS of the breast was a negative prognostic factor (HR: 2.35; p = 0.035). CONCLUSIONS: Different behaviors and prognoses depending on the primary site and etiology should be considered for the treatment of this heterogeneous disease. In cutaneous angiosarcomas of the head/neck and postradiation angiosarcomas of the breast, local recurrence seems to have a crucial impact on OS. Therefore, improved local therapies and local tumor staging may have to be implemented. However, in deep soft tissue angiosarcomas, distant recurrence seems to have a major influence on prognosis, which indicates a benefit of additional perioperative chemotherapy.

[Strategic approach to pathological fractures]. / Strategisches Vorgehen bei pathologischen Frakturen.

Pathological tumor-associated fractures are overall rare. They can occur in every age group and every bone. Although tumor-related fractures only form a small proportion of bone fractures, the early recognition of the cause of the fracture and treatment according to oncological guidelines are of enormous importance for affected patients. False treatment is frequently associated with far-reaching negative consequences with respect to the course of the disease. The great challenge is not the expeditious surgical treatment but much more the adequate diagnostics and the incorporation of local fracture treatment into an interdisciplinary overall oncological concept.

Evaluation of the Predictive Potential of 18F-FDG PET and DWI Data Sets for Relevant Prognostic Parameters of Primary Soft-Tissue Sarcomas.

BACKGROUND: To evaluate the potential of simultaneously acquired 18F-FDG PET- and MR-derived quantitative imaging data sets of primary soft-tissue sarcomas for the prediction of neoadjuvant treatment response, the metastatic status and tumor grade. METHODS: A total of 52 patients with a high-risk soft-tissue sarcoma underwent a 18F-FDG PET/MR examination within one week before the start of neoadjuvant treatment. For each patient, the maximum tumor size, metabolic activity (SUVs), and diffusion-restriction (ADC values) of the tumor manifestations were determined. A Mann-Whitney-U test was used, and ROC analysis was performed to evaluate the potential to predict histopathological treatment response, the metastatic status or tumor grade. The results from the histopathological analysis served as reference standard. RESULTS: Soft-tissue sarcomas with a histopathological treatment response revealed a significantly higher metabolic activity than tumors in the non-responder group. In addition, grade 3 tumors showed a significant higher 18F-FDG uptake than grade 2 tumors. Furthermore, no significant correlation between the different outcome variables and tumor size or calculated ADC-values could be identified. CONCLUSION: Measurements of the metabolic activity of primary and untreated soft-tissue sarcomas could non-invasively deliver relevant information that may be used for treatment planning and risk-stratification of high-risk sarcoma patients in a pretherapeutic setting.

Highly Cancellous Titanium Alloy (TiAl6V4) Surfaces on Three-Dimensionally Printed, Custom-Made Intercalary Tibia Prostheses: Promising Short- to Intermediate-Term Results.

Custom-made, three-dimensionally-printed (3D) bone prostheses gain increasing importance in the reconstruction of bone defects after musculoskeletal tumor resections. They may allow preservation of little remaining bone stock and ensure joint or limb salvage. However, we believe that by constructing anatomy-imitating implants with highly cancellous titanium alloy (TiAl6V4) surfaces using 3D printing technology, further benefits such as functional enhancement and reduction of complications may be achieved. We present a case series of four patients reconstructed using custom-made, 3D-printed intercalary monobloc tibia prostheses treated between 2016 and 2020. The mean patient age at operation was 30 years. Tumor resections were performed for Ewing sarcoma (n = 2), high-grade undifferentiated pleomorphic bone sarcoma (n = 1) and adamantinoma (n = 1). Mean resection length was 17.5 cm and mean operation time 147 min. All patients achieved full weight-bearing and limb salvage at a mean follow-up of 21.25 months. One patient developed a non-union at the proximal bone-implant interface. Alteration of implant design prevented non-union in later patients. Mean MSTS and TESS scores were 23.5 and 88. 3D-printed, custom-made intercalary tibia prostheses achieved joint and limb salvage in this case series despite high, published complication rates for biological and endoprosthetic reconstructions of the diaphyseal and distal tibia. Ingrowth of soft tissues into the highly cancellous implant surface structure reduces dead space, enhances function, and appears promising in reducing complication rates.

Evaluation of 18F-FDG PET and DWI Datasets for Predicting Therapy Response of Soft-Tissue Sarcomas Under Neoadjuvant Isolated Limb Perfusion.

Our purpose was to evaluate and compare the clinical utility of simultaneously obtained quantitative 18F-FDG PET and diffusion-weighted MRI datasets for predicting the histopathologic response of soft-tissue sarcoma (STS) to neoadjuvant isolated limb perfusion (ILP). Methods: In total, 37 patients with a confirmed STS of the extremities underwent 18F-FDG PET/MRI before and after ILP with melphalan and tumor necrosis factor-α. For each patient, the maximum tumor size, metabolic activity (SUV), and diffusion restriction (apparent diffusion coefficient, ADC) were determined in pre- and posttherapeutic examinations, and percentage changes during treatment were calculated. Mann-Whitney U testing and receiver-operating-characteristic analysis were used to compare the results of the different quantitative parameters to predict the histopathologic response to therapy. Results from histopathologic analysis after tumor resection served as the reference standard, and patients were defined as responders or nonresponders based on the grading scale by Salzer-Kuntschik. Results: Histopathologic analysis categorized 22 (59%) patients as responders (grades I-III) and 15 (41%) as nonresponders (grades IV-VI). Under treatment, tumors in responders showed a mean reduction in size (-9.7%) and metabolic activity (SUVpeak, -51.9%; SUVmean, -43.8%), as well as an increase of the ADC values (ADCmin, +29.4%; ADCmean, +32.8%). The percentage changes in nonresponders were -6.2% in tumor size, -17.3% in SUVpeak, -13.9% in SUVmean, +15.3% in ADCmin, and +14.6% in ADCmean Changes in SUV and ADCmean significantly differed between responders and nonresponders (<0.01), whereas differences in tumor size and ADCmin did not (>0.05). The corresponding AUCs were 0.63 for tumor size, 0.87 for SUVpeak, 0.82 for SUVmean, 0.63 for ADCmin, 0.84 for ADCmean, and 0.89 for ratio of ADCmean to SUVpeakConclusion: PET- and MRI-derived quantitative parameters (SUV and ADCmean) and their combination performed well in predicting the histopathologic therapy response of STS to neoadjuvant ILP. Therefore, integrated PET/MRI could serve as a valuable tool for pretherapeutic assessment as well as monitoring of neoadjuvant treatment strategies of STS.

Efficacy of hyperthermic isolated limb perfusion in the treatment of locally recurrent high-grade soft tissue sarcoma of the extremities.

BACKGROUND: This novel study compared the use of tumor necrosis factor (TNF)-alpha and melphalan-based isolated limb perfusion (TM-ILP) to the standard treatment of locally recurrent soft tissue extremity sarcoma. The aim was to assess whether TM-ILP positively influences the recurrence-free survival of locally recurrent high-grade soft tissue sarcoma (STS) of the extremities. METHODS: We retrospectively analyzed our clinical database for patients with STS. Variables were analyzed using chi-square test or Mann-Whitney rank-sum test. Furthermore, Kaplan-Meier survival plots were calculated and a proportional hazard regression model was developed. RESULTS: Out of 448 patients with extraabdominal STS treated between August 2012 and December 2015, 52 cases involving 47 patients had locally recurrent STS. Twenty-eight of these patients were treated with TM-ILP prior to surgical resection (TM-ILP-group), and 24 were treated with standard therapy (without TM-ILP). The 3-year recurrence-free survival for the TM-ILP-group was estimated at 75% (95% confidence interval (CI), 71.5-78.5). Local recurrence-free survival in the standard group was significantly lower (LRFS: 43.4%, 95% CI 38.7-48.1, p = 0.026). Multivariable analysis revealed resection with negative margins, lower number of previous recurrences, and TM-ILP as positive predictors for recurrence-free survival. CONCLUSIONS: TM-ILP and consecutive resection of residual tumor with negative resection margins significantly improves local recurrence-free survival for patients with a first local recurrence of high-grade STS in the extremities.