LUMiC Endoprosthetic Reconstruction of Periacetabular Tumor Defects: A Multicenter Follow-up Study.

BACKGROUND: We previously reported promising early results for periacetabular tumor reconstructions using the LUMiC prosthesis. The current study evaluates mid-term complications, revision rates, cumulative incidence of implant revision, and risk factors for complications in a multicenter cohort. METHODS: We assessed patients in whom a tumor defect after type P1b+2, P2, P2+3, or P1b+2+3 internal hemipelvectomy was reconstructed with a LUMiC prosthesis during the period of 2008 to 2022. Complications were reported according to the Henderson classification. Competing risks models were used to estimate the cumulative incidence of implant revision for mechanical and nonmechanical reasons, and reoperations for any complication. Cox models were used to study the effect of risk factors on dislocation and infection. RESULTS: One hundred and sixty-six patients (median follow-up, 4.2 years [interquartile range, 2.6 to 7.6 years]) were included. A total of 114 (69%) were treated for a primary malignant tumor, 46 (28%) for metastatic carcinoma, 5 (3%) for a benign aggressive lesion, and 1 (1%) for another reason. One hundred and sixty-five reoperations were performed in 82 (49%) of the patients; 104 (63%) of the reoperations were within 6 months. Thirty-two (19%) of 166 implants were revised: 13 (8%) for mechanical reasons, mainly dislocation (n = 5, 3%), and 19 (11%) for nonmechanical reasons, mainly periprosthetic joint infection (PJI) (n = 15, 9%). The cumulative incidences of revision for mechanical reasons and PJI (Henderson 1 to 4) at 2, 5, and 10 years were 11% (95% confidence interval [CI], 7% to 17%), 18% (12% to 25%), and 24% (16% to 33%), respectively. Previous surgery at the same site was associated with an increased dislocation risk (cause-specific hazard ratio [HRCS], 3.0 [95% CI, 1.5 to 6.4]; p < 0.01), and resections involving the P3 region were associated with an increased infection risk (HRCS, 2.5 [95% CI, 1.4 to 4.7]; p < 0.01). CONCLUSIONS: Despite a substantial reoperation risk, the LUMiC prosthesis demonstrated its durability in the mid-term, with a low mechanical revision rate and most patients retaining their primary implant. Most complications occur in the first postoperative months. Patients with previous surgery at the same site had an increased dislocation risk and might benefit from more conservative rehabilitation and aftercare. Measures should be aimed at reducing the PJI risk, especially in resections involving the P3 region. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Small cell osteosarcoma versus fusion-driven round cell sarcomas of bone: retrospective clinical, radiological, pathological, and (epi)genetic comparison with clinical implications.

Small cell osteosarcoma (SCOS), a variant of conventional high-grade osteosarcoma (COS), may mimic fusion-driven round cell sarcomas (FDRCS) by overlapping clinico-radiological and histomorphological/immunohistochemical characteristics, hampering accurate diagnosis and consequently proper therapy. We retrospectively analyzed decalcified formalin-fixed paraffin-embedded (FFPE) samples of 18 bone tumors primarily diagnosed as SCOS by methylation profiling, fusion gene analysis, and immunohistochemistry.In eight cases, the diagnosis of SCOS was maintained, and in 10 cases it was changed into FDRCS, including three Ewing sarcomas (EWSR1::FLI1 in two cases and no identified fusion gene in the third case), two sarcomas with BCOR alterations (KMT2D::BCOR, CCNB3::BCOR, respectively), three mesenchymal chondrosarcomas (HEY1::NCOA2 in two cases and one case with insufficient RNA quality), and two sclerosing epithelioid fibrosarcomas (FUS::CREBL3 and EWSR1 rearrangement, respectively).Histologically, SCOS usually possessed more pleomorphic cells in contrast to the FDRCS showing mainly monomorphic cellular features. However, osteoid was seen in the latter tumors as well, often associated with slight pleomorphism. Also, the immunohistochemical profile (CD99, SATB2, and BCOR) overlapped.Clinically and radiologically, similarities between SCOS and FDRCS were observed, with by imaging only minimal presence or lack of (mineralized) osteoid in most of the SCOSs.In conclusion, discrimination of SCOS, epigenetically related to COS, versus FDRCS of bone can be challenging but is important due to different biology and therefore therapeutic strategies. Methylation profiling is a reliable and robust diagnostic test especially on decalcified FFPE material. Subsequent fusion gene analysis and/or use of specific immunohistochemical surrogate markers can be used to substantiate the diagnosis.

Changes in Health-Related Quality of Life following Surgery in Patients with High-Grade Extremity Soft-Tissue Sarcoma: A Prospective Longitudinal Study.

INTRODUCTION: Changes in health-related quality of life (HRQoL) during the diagnostic and treatment trajectory of high-grade extremity soft-tissue sarcoma (eSTS) has rarely been investigated for adults (18-65 y) and the elderly (aged ≥65 y), despite a potential variation in challenges from diverse levels of physical, social, or work-related activities. This study assesses HRQoL from time of diagnosis to one year thereafter among adults and the elderly with eSTS. METHODS: HRQoL of participants from the VALUE-PERSARC trial (n = 97) was assessed at diagnosis and 3, 6 and 12 months thereafter, utilizing the PROMIS Global Health (GH), PROMIS Physical Function (PF) and EQ-5D-5L. RESULTS: Over time, similar patterns were observed in all HRQoL measures, i.e., lower HRQoL scores than the Dutch population at baseline (PROMIS-PF:46.8, PROMIS GH-Mental:47.3, GH-Physical:46.2, EQ-5D-5L:0.76, EQ-VAS:72.6), a decrease at 3 months, followed by an upward trend to reach similar scores as the general population at 12 months (PROMIS-PF:49.9, PROMIS GH-Physical:50.1, EQ-5D-5L:0.84, EQ-VAS:81.5), except for the PROMIS GH-Mental (47.5), where scores remained lower than the general population mean (T = 50). Except for the PROMIS-PF, no age-related differences were observed. CONCLUSIONS: On average, eSTS patients recover well physically from surgery, yet the mental component demonstrates no progression, irrespective of age. These results underscore the importance of comprehensive care addressing both physical and mental health.

Active surveillance of diffuse-type tenosynovial giant cell tumors: A retrospective, multicenter cohort study.

BACKGROUND: Diffuse-type tenosynovial giant cell tumor (D-TGCT) is a mono-articular, soft-tissue tumor. Although it can behave locally aggressively, D-TGCT is a non-malignant disease. This is the first study describing the natural course of D-TGCT and evaluating active surveillance as possible treatment strategy. METHODS: This retrospective, multicenter study included therapy naïve patients with D-TGCT from eight sarcoma centers worldwide between 2000 and 2019. Patients initially managed by active surveillance following their first consultation were eligible. Data regarding the radiological and clinical course and subsequent treatments were collected. RESULTS: Sixty-one patients with primary D-TGCT were initially managed by active surveillance. Fifty-nine patients had an MRI performed around first consultation: D-TGCT was located intra-articular in most patients (n = 56; 95 %) and extra-articular in 14 cases (24 %). At baseline, osteoarthritis was observed in 13 patients (22 %) on MRI. Most of the patients' reported symptoms: pain (n = 43; 70 %), swelling (n = 33; 54 %). Eight patients (13 %) were asymptomatic. Follow-up data were available for 58 patients; the median follow-up was 28 months. Twenty-one patients (36 %) had radiological progression after 21 months (median). Eight of 45 patients (18 %) without osteoarthritis at baseline developed osteoarthritis during follow-up. Thirty-seven patients (64 %) did not clinically deteriorate during follow-up. Finally, eighteen patients (31 %) required a subsequent treatment. CONCLUSION: Active surveillance can be considered adequate for selected therapy naïve D-TGCT patients. Although follow-up data was limited, almost two-thirds of the patients remained progression-free, and 69 % did not need treatment during the follow-up period. However, one-fifth of patients developed secondary osteoarthritis. Prospective studies on active surveillance are warranted.

Evaluation of response to neoadjuvant chemotherapy in osteosarcoma using dynamic contrast-enhanced MRI: development and external validation of a model.

OBJECTIVE: To identify which dynamic contrast-enhanced (DCE-)MRI features best predict histological response to neoadjuvant chemotherapy in patients with an osteosarcoma. METHODS: Patients with osteosarcoma who underwent DCE-MRI before and after neoadjuvant chemotherapy prior to resection were retrospectively included at two different centers. Data from the center with the larger cohort (training cohort) was used to identify which method for region-of-interest selection (whole slab or focal area method) and which change in DCE-MRI features (time to enhancement, wash-in rate, maximum relative enhancement and area under the curve) gave the most accurate prediction of histological response. Models were created using logistic regression and cross-validated. The most accurate model was then externally validated using data from the other center (test cohort). RESULTS: Fifty-five (27 poor response) and 30 (19 poor response) patients were included in training and test cohorts, respectively. Intraclass correlation coefficient of relative DCE-MRI features ranged 0.81-0.97 with the whole slab and 0.57-0.85 with the focal area segmentation method. Poor histological response was best predicted with the whole slab segmentation method using a single feature threshold, relative wash-in rate <2.3. Mean accuracy was 0.85 (95%CI: 0.75-0.95), and area under the receiver operating characteristic curve (AUC-index) was 0.93 (95%CI: 0.86-1.00). In external validation, accuracy and AUC-index were 0.80 and 0.80. CONCLUSION: In this study, a relative wash-in rate of <2.3 determined with the whole slab segmentation method predicted histological response to neoadjuvant chemotherapy in osteosarcoma. Consistent performance was observed in an external test cohort.

Wait-and-scan: an alternative for curettage in atypical cartilaginous tumours of the long bones.

Aims: Due to its indolent clinical behaviour, the treatment paradigm of atypical cartilaginous tumours (ACTs) in the long bones is slowly shifting from intralesional resection (curettage) and local adjuvants, towards active surveillance through wait-and-scan follow-up. In this retrospective cohort study performed in a tertiary referral centre, we studied the natural behaviour of ACT lesions by active surveillance with MRI. Clinical symptoms were not considered in the surveillance programme. Methods: The aim of this study was to see whether active surveillance is safe regarding malignant degeneration and local progression. In total, 117 patients were evaluated with MRI assessing growth, cortical destruction, endosteal scalloping, periosteal reaction, relation to the cortex, and perilesional bone marrow oedema. Patients received up to six follow-up scans. Results: At the time of the first follow-up MRI, 8% of the lesions showed growth (n = 9), 86% remained stable (101), and 6% decreased in size (n = 7). During the third follow-up, with a mean follow-up time of 60 months (SD 23), 24 patients were scanned, of whom 13% had lesions that had grown and 13% lesions that had decreased in size. After 96 months (SD 37), at the sixth follow-up MRI, 100% of the lesions remained stable. None of the lesions showed malignant progression and although some lesions grew in size (mean 1 mm (SD 0.8)), no malignant progression occurred. Conclusion: We conclude that active surveillance with MRI is safe for ACTs in the long bones in the short- and mid-term follow-up.

(Cost-)effectiveness of an individualised risk prediction tool (PERSARC) on patient's knowledge and decisional conflict among soft-tissue sarcomas patients: protocol for a parallel cluster randomised trial (the VALUE-PERSARC study).

INTRODUCTION: Current treatment decision-making in high-grade soft-tissue sarcoma (STS) care is not informed by individualised risks for different treatment options and patients' preferences. Risk prediction tools may provide patients and professionals insight in personalised risks and benefits for different treatment options and thereby potentially increase patients' knowledge and reduce decisional conflict. The VALUE-PERSARC study aims to assess the (cost-)effectiveness of a personalised risk assessment tool (PERSARC) to increase patients' knowledge about risks and benefits of treatment options and to reduce decisional conflict in comparison with usual care in high-grade extremity STS patients. METHODS: The VALUE-PERSARC study is a parallel cluster randomised control trial that aims to include at least 120 primarily diagnosed high-grade extremity STS patients in 6 Dutch hospitals. Eligible patients (≥18 years) are those without a treatment plan and treated with curative intent. Patients with sarcoma subtypes or treatment options not mentioned in PERSARC are unable to participate. Hospitals will be randomised between usual care (control) or care with the use of PERSARC (intervention). In the intervention condition, PERSARC will be used by STS professionals in multidisciplinary tumour boards to guide treatment advice and in patient consultations, where the oncological/orthopaedic surgeon informs the patient about his/her diagnosis and discusses benefits and harms of all relevant treatment options. The primary outcomes are patients' knowledge about risks and benefits of treatment options and decisional conflict (Decisional Conflict Scale) 1 week after the treatment decision has been made. Secondary outcomes will be evaluated using questionnaires, 1 week and 3, 6 and 12 months after the treatment decision. Data will be analysed following an intention-to-treat approach using a linear mixed model and taking into account clustering of patients within hospitals. ETHICS AND DISSEMINATION: The Medical Ethical Committee Leiden-Den Haag-Delft (METC-LDD) approved this protocol (NL76563.058.21). The results of this study will be reported in a peer-review journal. TRIAL REGISTRATION NUMBER: NL9160, NCT05741944.

Follow-Up after Curative Surgical Treatment of Soft-Tissue Sarcoma for Early Detection of Recurrence: Which Patients Have More or Fewer Visits than Advised in Guidelines?

INTRODUCTION: Follow-up (FU) in soft-tissue sarcoma (STS) patients is designed for early detection of disease recurrence. Current guidelines are not evidenced-based and not tailored to patient or tumor characteristics, so they remain debated, particularly given concerns about cost, radiation frequency, and over-testing. This study assesses the extent to which STS patients received guideline-concordant FU and to characterize which type of patients received more or fewer visits than advised. METHODS: All STS patients surgically treated at the Leiden University Medical Center between 2000-2020 were included. For each patient, along with individual characteristics, all radiological examinations from FU start up to 5 years were included and compared to guidelines. Recurrence was defined as local/regional recurrence or metastasis. RESULTS: A total of 394 patients was included, of whom 250 patients had a high-grade tumor (63.5%). Only 24% of patients received the advised three FU visits in the first year. More FU visits were observed in younger patients and those diagnosed with a high-grade tumor. Among patients with a recurrence, 10% received fewer visits than advised, while 28% of patients without a recurrence received more visits than advised. CONCLUSIONS: A minority of STS patients received guideline-concordant FU visits, suggesting that clinicians seem to incorporate recurrence risk in decisions on FU frequency.

Carbon-fibre plates for traumatic and (impending) pathological fracture fixation: Where do we stand? A systematic review.

BACKGROUND: Carbon-fibre (CF) plates are increasingly used for fracture fixation. This systematic review evaluated complications associated with CF plate fixation. It also compared outcomes of patients treated with CF plates versus metal plates, aiming to determine if CF plates offered comparable results. The study hypothesized that CF plates display similar complication rates and clinical outcomes as metal plates for fracture fixation. METHODS: The study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The following databases were searched from database inception until June 2023: PubMed, MEDLINE, Embase, Web of Science, Cochrane Library, Emcare, Academic Search Premier and Google Scholar. Studies reporting on clinical and radiological outcomes of patients treated with CF plates for traumatic fractures and (impending) pathological fractures were included. Study quality was assessed, and complications were documented as number and percentage per anatomic region. RESULTS: A total of 27 studies of moderate to very low quality of evidence were included. Of these, 22 studies (800 patients, median follow-up 12 months) focused on traumatic fractures, and 5 studies (102 patients, median follow-up 12 months) on (impending) pathological fractures. A total of 11 studies (497 patients, median follow-up 16 months) compared CF plates with metal plates. Regarding traumatic fractures, the following complications were mostly reported: soft tissue complications (52 out of 391; 13%) for the humerus, structural complications (6 out of 291; 2%) for the distal radius, nonunion and structural complication (1 out of 34; 3%) for the femur, and infection (4 out of 104; 4%) for the ankle. For (impending) pathological fractures, the most frequently reported complications were infections (2 out of 14; 14%) for the humerus and structural complication (6 out of 86; 7%) for the femur/tibia. Comparative studies reported mixed results, although the majority (7 out of 11; 64%) reported no significant differences in clinical or radiological outcomes between patients treated with CF or metal plates. CONCLUSION: This systematic review did not reveal a concerning number of complications related to CF plate fixation. Comparative studies showed no significant differences between CF plates and metal plates for traumatic fracture fixation. Therefore, CF plates appear to be a viable alternative to metal plates. However, high-quality randomized controlled trials (RCTs) with long-term follow-up are strongly recommended to provide additional evidence supporting the use of CF plates. LEVEL OF EVIDENCE: III, systematic review.

Multimodal management of tenosynovial giant cell tumors (TGCT) in the landscape of new druggable targets.

Tenosynovial giant cell tumor (TGCT) is a rare, benign, locally aggressive synovial based neoplastic process that can result in functional debilitation and end-stage arthrtitis. Although surgical resection is the primary treatment modality, novel systemic therapies are emerging as part of the multimodal armamentarium for patients with unresectable or complex disease burden. This review discusses the pathogenesis of TGCT, potential druggable targets and therapeutic approaches. It also evaluates the safety and efficacy of different systemic therapies.

BRAF V600E is associated with higher incidence of second cancers in adults with Langerhans cell histiocytosis.

In this retrospective study, BRAF mutation status did not correlate with disease extent or (event-free) survival in 156 adults with Langerhans cell histiocytosis. BRAFV600E was associated with an increased incidence of second malignancies, often comprising hematological cancers, which may be clonally related.

Evaluation of Potential Targets for Fluorescence-Guided Surgery in Pediatric Ewing Sarcoma: A Preclinical Proof-of-Concept Study.

Fluorescence-guided surgery (FGS), based on fluorescent tracers binding to tumor-specific biomarkers, could assist surgeons to achieve complete tumor resections. This study evaluated potential biomarkers for FGS in pediatric Ewing sarcoma (ES). Immunohistochemistry (IHC) was performed to assess CD99, CXCR4, CD117, NPY-R-Y1, and IGF-1R expression in ES biopsies and resection specimens. LINGO-1 and GD2 evaluation did not work on the acquired tissue. Based on the immunoreactive scores, anti-CD99 and anti-CD117 were evaluated for binding specificity using flow cytometry and immunofluorescence microscopy. Anti-GD2, a tracer in the developmental phase, was also tested. These three tracers were topically applied to a freshly resected ES tumor and adjacent healthy tissue. IHC demonstrated moderate/strong CD99 and CD117 expression in ES tumor samples, while adjacent healthy tissue had limited expression. Flow cytometry and immunofluorescence microscopy confirmed high CD99 expression, along with low/moderate CD117 and low GD2 expression, in ES cell lines. Topical anti-CD99 and anti-GD2 application on ES tumor showed fluorescence, while anti-CD117 did not show fluorescence for this patient. In conclusion, CD99-targeting tracers hold promise for FGS of ES. CD117 and GD2 tracers could be potential alternatives. The next step towards development of ES-specific FGS tracers could be ex vivo topical application experiments on a large cohort of ES patients.

Health-Related Quality of Life of Bone and Soft-Tissue Tumor Patients around the Time of Diagnosis.

BACKGROUND: Bone and soft-tissue tumor patients experience long-lasting physical and psychological challenges. It is unknown to what extent Health-Related Quality of Life (HRQoL) is already affected during the diagnostic process. This study assesses the HRQoL of bone and soft-tissue tumor patients around time of diagnosis and explores which patient or tumor characteristics are associated with a reduced HRQoL. METHODS: All patients with a suspected benign/malignant bone tumor (BT), benign soft-tissue tumor (STT), or malignant soft-tissue sarcoma (STS) visiting the Leiden University Medical Center between 2016 and 2020 were invited to complete the Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item profile questionnaire. Mean scores of all included patients and per diagnosis group were compared to mean scores of the general population using one-sample t-tests. RESULTS: Overall, patients (n = 637) reported statistically significantly worse HRQoL-scores on anxiety (51.3 ± 9.6), pain (55.3 ± 10.1), physical functioning (46.0 ± 9.7), and social functioning (48.1 ± 10.8) with the difference in pain and physical functioning being clinically relevant (based on a 3-point difference on t-metric). HRQoL-scores differed between diagnosis subgroups, i.e., patients with malignant tumors had higher anxiety levels and experienced more pain, where patients with bone tumors had worse physical functioning. CONCLUSION: The HRQoL of patients with suspected bone and soft-tissue tumors is already affected during the diagnostic process.

Coxa Vara Deformity in Fibrous Dysplasia/McCune-Albright Syndrome: Prevalence, Natural History and Risk Factors: A Two-Center Study.

This study aimed to evaluate the prevalence of and risk factors for coxa vara deformity in patients with fibrous dysplasia/McCune-Albright syndrome (FD/MAS). This study was conducted at the National Institutes of Health and Leiden University Medical Center. All patients with any subtype of FD/MAS, FD involving the proximal femur, one or more X-rays available and age <30 years were included. X-rays were scored for the neck-shaft angle (NSA). Varus deformity was defined as NSA <110 degrees or >10 degrees below age-specific values. Risk factors for deformity were assessed by nested case-control analysis, comparing patients and femurs with and without deformity, and by linear mixed effects model, modeling temporal NSA decrease (the natural course of the NSA) in non-operated femurs with two or more X-rays. Assessed variables included growth hormone excess, hyperthyroidism, hypophosphatemia, >25% of the femur affected, calcar destruction, radiolucency, and bilateral involvement. In total 180 patients were studied, 57% female. Mean ± SD baseline age was 13.6 ± 7.5 years; median follow-up 5.4 (interquartile range [IQR], 11.1) years. Sixty-three percent (63%) were diagnosed with MAS. A total of 94 patients were affected bilaterally; 274 FD femurs were analyzed; 99 femurs had a varus deformity (36%). In the nested case-control analysis, risk factors were as follows: presence of MAS (p < 0.001), hyperthyroidism (p < 0.001), hypophosphatemia (p < 0.001), high percentage of femur affected (p < 0.001), and calcar destruction (p < 0.001). The linear mixed effects model included 114 femurs, identified risk factors were: growth hormone excess (ß = 7.2, p = 0.013), hyperthyroidism (ß = 11.3, p < 0.001), >25% of the femur affected (ß = 13.2, p = 0.046), calcar destruction (ß = 8.3, p = 0.004), radiolucency (ß = 3.9, p = 0.009), and bilateral involvement (ß = 9.8, p = 0.010). Visual inspection of the graph of the model demonstrated most progression of deformity if NSA <120 degrees with age < 15 years. In conclusion, in tertiary care centers, the prevalence of FD/MAS coxa vara deformity was 36%. Risk factors included presence of MAS, high percentage of femur affected, calcar destruction, radiolucency, NSA <120 degrees and age < 15 years. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Impact of Age at Diagnosis on Cardiotoxicity in High-Grade Osteosarcoma and Ewing Sarcoma Patients.

Background: Osteosarcoma and Ewing sarcoma patients face a significant risk of cardiotoxicity as defined by left ventricular dysfunction and heart failure (HF). Objectives: This study sought to evaluate the association between age at sarcoma diagnosis and incident HF. Methods: A retrospective cohort study was performed at the largest sarcoma center in the Netherlands among patients with an osteosarcoma or Ewing sarcoma. All patients were diagnosed and treated over a 36-year period (1982-2018) and followed until August 2021. Incident HF was adjudicated through the universal definition of heart failure. Determinants including age at diagnosis, doxorubicin dose, and cardiovascular risk factors were entered as fixed or time-dependent covariates into a cause-specific Cox model to assess their impact on incident HF. Results: The study population consisted of 528 patients with a median age at diagnosis of 19 years (Q1-Q3: 15-30 years). Over a median follow-up time of 13.2 years (Q1-Q3: 12.5-14.9 years), 18 patients developed HF with an estimated cumulative incidence of 5.9% (95% CI: 2.8%-9.1%). In a multivariable model, age at diagnosis (HR: 1.23; 95% CI: 1.06-1.43) per 5-year increase, doxorubicin dose per 10-mg/m2 increase (HR: 1.13; 95% CI: 1.03-1.24), and female sex (HR: 3.17; 95% CI: 1.11-9.10) were associated with HF. Conclusions: In a large cohort of sarcoma patients, we found that patients diagnosed at an older age are more prone to develop HF.

Immunohistochemical Evaluation of Candidate Biomarkers for Fluorescence-Guided Surgery of Myxofibrosarcoma Using an Objective Scoring Method.

INTRODUCTION: Myxofibrosarcoma (MFS) is the most common soft-tissue sarcoma subtype in elderly patients. Local recurrence (LR) remains a major concern as the lack of intraoperative guidance and an infiltrative growth pattern with long, slender tails hamper surgeons' ability to achieve adequate resection margins for MFS. Fluorescence-guided surgery (FGS) could overcome this concern by delineating tumor tissue during surgery. One of the most important steps to successful FGS is to define a tumor-specific biomarker that is highly overexpressed in tumor tissue while low or absent in adjacent healthy tissue. The aim of this study is to evaluate the expression of eight previously selected promising biomarkers for FGS in MFS tissue samples with adjacent healthy tissue using immunohistochemistry (IHC). METHODS: The following eight biomarkers were stained in seventeen paraffin-embedded MFS samples: tumor endothelial marker-1 (TEM-1, also known as endosialin/CD248), vascular endothelial growth factor receptor-1 (VEGFR-1, also known as Flt-1), vascular endothelial growth factor receptor-2 (VEGFR-2, also known as Flk1), vascular endothelial growth factor-A (VEGF-A), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), platelet derived growth factor receptor-α (PDGFR-α), and cluster of differentiation 40 (CD40, also known as TNFRSF5). A pathologist specializing in sarcoma annotated the margin between the tumor and adjacent healthy tissue in each MFS tissue sample. Subsequently, we used an objective IHC scoring method to assess and compare the difference in staining intensity between the tumor and adjacent healthy tissue, which is crucial for the use of FGS. RESULTS: TEM-1, VEGF-A, and PDGFR-α stained all MFS tumors, while the other biomarkers did not show expression in all MFS tumors. Ultimately, TEM-1 was identified as the most suitable biomarker for FGS in MFS based on higher tumor-to-background (TBR) staining intensity compared to VEGF-A and PDGFR-α, regardless of preoperative therapy. CONCLUSION: TEM-1-targeted FGS tracers should be further investigated to optimize MFS treatment.

One-Stage Synovectomies Result in Improved Short-Term Outcomes Compared to Two-Stage Synovectomies of Diffuse-Type Tenosynovial Giant Cell Tumor (D-TGCT) of the Knee: A Multicenter, Retrospective, Cohort Study.

Diffuse-type tenosynovial giant cell tumors' (D-TGCTs) intra- and extra-articular expansion about the knee often necessitates an anterior and posterior surgical approach to facilitate an extensive synovectomy. There is no consensus on whether two-sided synovectomies should be performed in one or two stages. This retrospective study included 191 D-TGCT patients from nine sarcoma centers worldwide to compare the postoperative short-term outcomes between both treatments. Secondary outcomes were rates of radiological progression and subsequent treatments. Between 2000 and 2020, 117 patients underwent one-stage and 74 patients underwent two-stage synovectomies. The maximum range of motion achieved within one year postoperatively was similar (flexion 123-120°, p = 0.109; extension 0°, p = 0.093). Patients undergoing two-stage synovectomies stayed longer in the hospital (6 vs. 4 days, p < 0.0001). Complications occurred more often after two-stage synovectomies, although this was not statistically different (36% vs. 24%, p = 0.095). Patients treated with two-stage synovectomies exhibited more radiological progression and required subsequent treatments more often than patients treated with one-stage synovectomies (52% vs. 37%, p = 0.036) (54% vs. 34%, p = 0.007). In conclusion, D-TGCT of the knee requiring two-side synovectomies should be treated by one-stage synovectomies if feasible, since patients achieve a similar range of motion, do not have more complications, but stay for a shorter time in the hospital.

Impaired social functioning in adolescent and young adult sarcoma survivors: Prevalence and risk factors.

BACKGROUND: Sarcomas account for almost 11% of all cancers in adolescents and young adults (AYAs; 18-39 years). AYAs are increasingly recognized as a distinct oncological age group with its own psychosocial challenges and biological characteristics. Social functioning has been shown to be one of the most severely affected domains of health-related quality of life in AYA cancer survivors. This study aims to identify AYA sarcoma survivors with impaired social functioning (ISF) and determine clinical and psychosocial factors associated with ISF. METHODS: AYAs from the population-based cross-sectional sarcoma survivorship study (SURVSARC) were included (n = 176). ISF was determined according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 social functioning scale, and age- and sex-matched norm data were used as reference. RESULTS: The median time since diagnosis was 6.2 years (range, 1.8-11.2). More than one-quarter (28%) of AYA sarcoma survivors experienced ISF. Older age, higher tumor stage, comorbidities, lower experienced social support, uncertainty in relationships, feeling less attractive, sexual inactivity, unemployment, and financial difficulties were associated with ISF. In a multivariable analysis, unemployment (OR, 3.719; 95% CI, 1.261-10.967) and having to make lifestyle changes because of financial problems caused by one's physical condition or medical treatment (OR, 3.394; 95% CI, 1.118-10.300) were associated with ISF; better experienced social support was associated with non-ISF (OR, 0.739; 95% CI, 0.570-0.957). CONCLUSION: More than one-quarter of AYA sarcoma survivors experience ISF long after diagnosis. These results emphasize the importance of follow-up care that is not only disease-oriented but also focuses on the psychological and social domains. PLAIN LANGUAGE SUMMARY: Sarcomas account for almost 11% of all cancers in adolescents and young adults (AYAs; 18-39 years). The AYA group is increasingly recognized as a distinct oncological age group with its own psychosocial challenges and biological characteristics. Social functioning has been shown to be severely affected in AYA cancer survivors. A population-based questionnaire study to identify AYA sarcoma survivors with impaired social functioning (ISF) and determine factors associated with ISF was conducted. More than one-quarter of AYA sarcoma survivors experience ISF long after diagnosis. These results emphasize the importance of follow-up care that is not only disease-orientated but also focuses on the psychological and social domains.

MRI of diffuse-type tenosynovial giant cell tumour in the knee: a guide for diagnosis and treatment response assessment.

Tenosynovial giant cell tumour (TGCT) is a rare soft-tissue tumour originating from synovial lining of joints, bursae and tendon sheaths. The tumour comprises two subtypes: the localised-type (L-TGCT) is characterised by a single, well-defined lesion, whereas the diffuse-type (D-TGCT) consists of multiple lesions without clear margins. D-TGCT was previously known as pigmented villonodular synovitis. Although benign, TGCT can behave locally aggressive, especially the diffuse-type. Magnetic resonance imaging (MRI) is the modality of choice to diagnose TGCT and discriminate between subtypes. MRI can also provide a preoperative map before synovectomy, the mainstay of treatment. Finally, since the arrival of colony-stimulating factor 1-receptor inhibitors, a novel systemic therapy for D-TGCT patients with relapsed or inoperable disease, MRI is key in assessing treatment response. As recurrence after treatment of D-TGCT occurs more often than in L-TGCT, follow-up imaging plays an important role in D-TGCT. Reading follow-up MRIs of these diffuse synovial tumours may be a daunting task. Therefore, this educational review focuses on MRI findings in D-TGCT of the knee, which represents the most involved joint site (approximately 70% of patients). We aim to provide a systematic approach to assess the knee synovial recesses, highlight D-TGCT imaging findings, and combine these into a structured report. In addition, differential diagnoses mimicking D-TGCT, potential pitfalls and evaluation of tumour response following systemic therapies are discussed. Finally, we propose automated volumetric quantification of D-TGCT as the next step in quantitative treatment response assessment as an alternative to current radiological assessment criteria.

Reconstructive Strategies in Pediatric Patients after Oncological Chest Wall Resection: A Systematic Review.

An appropriate reconstruction strategy after surgical resection of chest wall tumors in children is important to optimize outcomes, but there is no consensus on the ideal approach. The aim of this study was to provide an up-to-date systematic review of the literature for different reconstruction strategies for chest wall defects in patients less than 18 years old. A systematic literature search of the complete available literature was performed and results were analyzed. A total of 22 articles were included in the analysis, which described a total of 130 chest wall reconstructions. All were retrospective analyses, including eight case reports. Reconstructive options were divided into primary closure (n = 21 [16.2%]), use of nonautologous materials (n = 83 [63.8%]), autologous tissue repair (n = 2 [1.5%]), or a combination of the latter two (n = 24 [18.5%]). Quality of evidence was poor, and the results mostly heterogeneous. Reconstruction of chest wall defects can be divided into four major categories, with each category including its own advantages and disadvantages. There is a need for higher quality evidence and guidelines, to be able to report uniformly on treatment outcomes and assess the appropriate reconstruction strategy.