Characterization of sacral chordoma and differential diagnosis from other sacral malignancy using [18F]FDG PET/CT.

2-Deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET)/computed tomography (CT) is known to be a helpful imaging modality for sacral chordoma, but its detailed characteristics have not been fully described. The purpose of our study was to identify the [18F]FDG PET/CT imaging characteristics of sacral chordoma and compare them with other sacral malignancy. This retrospective study included patients who underwent [18F]FDG PET/CT because of a mass involving the sacrum. Investigated visual findings included visual score and distribution, and semiquantitative parameters measured included standardized uptake values (SUVmax, SUVpeak, SUVmean), tumor-to-liver ratio (TLR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor size. Comparison studies and receiver operating characteristics (ROC) curve analysis were performed to differentiate between sacral chordoma and other sacral malignancy. Ten patients with sacral chordoma were finally included (M:F = 6:4, median age = 67 yr). On [18F]FDG PET/CT, sacral chordomas presented as a mass with minimal-moderate uptake with a usually heterogenous distribution. Compared with 12 patients with other sacral malignancies (M:F = 4:8, median age 42 yr), sacral chordoma showed a significantly lower TLR (median value 2.1 vs 6.3, P = .021). In ROC curve analysis, TLR showed the largest area under the curve (AUC) of 0.79 (cutoff ≤ 4.0; sensitivity 100.0%, specificity 58.3%; P = .004), and SUVmax showed the second largest AUC of 0.73 (cutoff ≤ 6.9; sensitivity 80.0%, specificity 66.7%; P = .034). [18F]FDG PET/CT of sacral chordoma showed minimal-moderate uptake. The TLR of [18F]FDG PET/CT was significantly lower than that of other sacral malignancy and was the most useful parameter for differentiating sacral chordoma, with the largest AUC. SUVmax could be another helpful semiquantitative parameter.

Favorable clinical efficacy of cytotoxic chemotherapy in patients with progressive desmoid tumors: a retrospective real-world study.

BACKGROUND: The real-world evidence about the efficacy of cytotoxic chemotherapy in desmoid tumors is still limited. We investigated the efficacy of chemotherapy in the treatment of recurrent or progressive desmoid tumors. METHODS: The patients with desmoid tumors who had received cytotoxic chemotherapy between November 2007 and June 2020 in two tertiary hospitals in Korea were reviewed. RESULTS: A total of 25 patients were included in the analysis. The most common primary tumor site was the intra-abdominal or pelvic cavity (56%), followed by the trunk and abdominal wall (24%), extremities (16%), and head and neck (4%). Sixty percent of the patients had familial adenomatous polyposis and 76% received doxorubicin plus dacarbazine. The objective response rate and disease control rate was 64% (95% confidence interval [CI]: 40.7-82.8) and 96% (95% CI: 77.2-99.9), respectively. With the median follow-up time of 55 months (95% CI: 41.0-68.2), the 3-year PFS rate was 65% (95% CI: 41.1-80.5), and the 3-year OS rate was 89% (95% CI: 63.8-97.3). Grade 3 or 4 hematologic adverse events were reported in 14 patients, all of which were manageable. CONCLUSION: Our real-world evidence suggests that doxorubicin-based cytotoxic chemotherapy can be an effective treatment option for recurrent and progressive desmoid tumors with respect to favorable clinical outcomes.

Enhancing local recurrence detection in patients with high-grade soft tissue sarcoma: value of short-term Ultrasonography added to post-operative MRI surveillance.

BACKGROUND: Limited data exist on the optimal postoperative surveillance protocol for high-grade soft tissue sarcoma, particularly regarding the optimal imaging modality and imaging interval for detecting local recurrence. This study aimed to assess the benefit of short-term postoperative ultrasonography (USG) for detecting local recurrence in patients with high-grade soft tissue sarcoma. METHODS: Patients with newly diagnosed high-grade soft tissue sarcoma who underwent surgical resection between January 2010 and June 2020 were included. Short-term USG was added to the follow-up protocol as a surveillance tool alongside routine magnetic resonance imaging (MRI). The primary outcome was the additional detection rate of short-term USG compared with routine MRI surveillance for early local recurrence detection. Subgroup analysis was performed to evaluate factors influencing USG detection rate. The additional detection rate of short-term USG for detection of metastatic lymph nodes was also evaluated. The secondary outcome was the false referral rate of short-term USG. RESULTS: In total, 198 patients (mean age ± standard deviation: 52.1 ± 15.8 years; 94 women) were included. Local recurrence occurred in 20 patients (10.1%; 20/198). Short-term USG detected local recurrence in advance of routine MRI visits in 7 out of 198 patients, resulting in an additional detection rate of 3.5% (95% CI: 1.7-7.1%). Subgroup analysis showed no significant difference in the short-term USG detection rate based on initial tumor characteristics, and receipt of radiotherapy or chemotherapy. Short-term USG additionally detected five of seven patients with metastatic lymph nodes [2.5% (95% CI, 1.1-5.8%, 5/198)]. The false referral rate of short-term USG was 3.5% (95% CI: 1.7-7.1%; 7/198). CONCLUSIONS: Short-term USG as part of postoperative surveillance for high-grade soft tissue sarcoma can enhance early detection of local tumor recurrence and metastatic lymphadenopathy. Early detection of local tumor recurrence could lead to a prompt surgical resection and aid in local disease control.

Detecting residual soft tissue sarcoma after unplanned excision; model-free analysis of dynamic contrast-enhanced MRI at short-term follow-up.

OBJECTIVES: To evaluate diagnostic utility of additional DCE-MRI for detecting residual soft tissue sarcomas (STS) after unplanned excision (UPE). METHODS: We retrospectively evaluated 32 patients with UPE of STS, followed by conventional MRI with DCE-MRI and wide excision (WE), between November 2019 and January 2022. Residual tumors on conventional MRI were categorized into three groups: Lesion-type-0, no abnormal enhancement, Lesion-type-1, an indeterminate lesion, and Lesion-type-2, a definite enhancing nodule. On DCE-MRI, ROIs were manually placed on enhancing areas of suspected residual tumor. The mean and 95th percentile values of AUC of time-intensity curve were calculated at 60, 90, and 120 s of Enhancement-cycle-1 and -2. Optimal DCE parameters were identified by ROC analysis. Diagnostic performance of conventional MRI and DCE-MRI was compared using McNemar's test. RESULTS: On WE, residual tumor was present in 23 (71.9%) of 32 patients. On MRI, Lesion-type-1 was found in 16/32 (50%) patients and Lesion-type-2 in 16/32 (50%). The optimal DCE parameter was the 95th percentile value of AUC at 120s of Enhancement-cycle-2. The sensitivity, specificity, and AUC were as follows: 65.2% (95% CI, 45.8-85.7%), 88.9% (CI, 68.4-100%), and 0.77 (CI, 0.62-0.92) for conventional MRI, and 100%, 55.6% (CI, 23.1-88.0%), and 0.78 (CI, 0.61-0.95) for combined conventional and DCE-MRI. CONCLUSIONS: Additional DCE-MRI aided in detecting residual STS after UPE, particularly in cases without definite soft tissue nodular enhancement. ADVANCES IN KNOWLEDGE: Close follow up may be suggested for patients showing abnormality in DCE-MRI, with more suspicion of residual tumor.

What are the resection accuracy and guide-fitting errors associated with 3D-printed, patient-specific resection guides for bone tumour resections?

AIMS: This study aimed to analyze the accuracy and errors associated with 3D-printed, patient-specific resection guides (3DP-PSRGs) used for bone tumour resection. METHODS: We retrospectively reviewed 29 bone tumour resections that used 3DP-PSRGs based on 3D CT and 3D MRI. We evaluated the resection amount errors and resection margin errors relative to the preoperative plans. Guide-fitting errors and guide distortion were evaluated intraoperatively and one month postoperatively, respectively. We categorized each of these error types into three grades (grade 1, < 1 mm; grade 2, 1 to 3 mm; and grade 3, > 3 mm) to evaluate the overall accuracy. RESULTS: The maximum resection amount error was 2 mm. Out of 29 resection amount errors, 15 (51.7%) were grade 1 errors and 14 (38.3%) were grade 2 errors. Complex resections were associated with higher-grade resection amount errors (p < 0.001). The actual resection margins correlated significantly with the planned margins; however, there were some discrepancies. The maximum guide-fitting error was 3 mm. There were 22 (75.9%), five (17.2%), and two (6.9%) grade 1, 2, and 3 guide-fitting errors, respectively. There was no significant association between complex resection and fitting error grades. The guide distortion after one month in all patients was rated as grade 1. CONCLUSION: In terms of the accurate resection amount according to the preoperative planning, 3DP-PSRGs can be a viable option for bone tumour resection. However, 3DP-PSRG use may be associated with resection margin length discrepancies relative to the planned margins. Such discrepancies should be considered when determining surgical margins. Therefore, a thorough evaluation of the preoperative imaging and surgical planning is still required, even if 3DP-PSRGs are to be used.Cite this article: Bone Joint J 2023;105-B(2):190-197.

High-dose chemotherapy followed by autologous stem cell transplantation in pediatric patients with relapsed osteosarcoma.

BACKGROUND: Patients with relapsed osteosarcoma have poor treatment outcomes. High-dose chemotherapy with autologous stem cell transplantation (HDCT/ASCT) has been used in several high-risk malignant solid tumors; however, few studies have evaluated their role in treating osteosarcoma. We evaluated the effectiveness of HDCT/ASCT in relapsed pediatric osteosarcoma cases. PROCEDURE: We retrospectively reviewed the medical records of 40 patients diagnosed with and treated for relapsed osteosarcoma at Asan Medical Center and Samsung Medical Center from January 1996 to July 2019. RESULTS: The median age of this cohort was 13.4 years (range: 6.1-18.2). The cohort's 5-year overall survival (OS) was 51.0% ± 0.1% during a median follow-up period of 67.5 months. Twenty-five patients (62.5%) achieved complete remission (CR) with salvage treatment, and the 5-year OS was 82.4% ± 0.1%, whereas none of the remaining 15 patients who did not achieve CR survived (p < .0001). Of the 25 CR cases, 15 underwent subsequent HDCT/ASCT. We compared the effect of HDCT/ASCT among patients who achieved CR. There were no significant differences in the 5-year OS outcomes between patients who did and did not receive HDCT/ASCT (83.9% ± 0.1%, 13/15 vs. 80.0% ± 0.1%, 8/10, respectively; p = .923). CONCLUSION: To our knowledge, we report the first comparative cohort study that proved HDCT/ASCT does not significantly improve survival outcomes in relapsed osteosarcoma. Achievement of CR remains the most crucial factor for good survival outcomes.

Management of talar lesions with cement augmentation and autologous bone graft.

BACKGROUND: Treatment of bone lesions involved with the articular cartilage at the talus is challenging. We report the management of talus lesions, particularly tumors and avascular necrosis (AVN), at the articular surface through treatment with cement augmentation and autologous bone graft. METHODS: Eight benign bone tumors and three cases of AVN were reviewed retrospectively at a mean follow-up of 56 months (range, 12-162). The mean age of all patients was 36.1 years old (range, 15-73) when assessed between February 2005 and November 2021. Curettage of tumorous and necrotic lesions resulted in significant bone defects filled with bone cement augmentation. Cartilage defects of the talar dome were supported with autologous cancellous bone graft. Tolerable weight-bearing ambulation was permitted immediately after surgery. Radiological and functional evaluations were recorded. RESULTS: We observed an increase in the average The American Orthopaedic Foot and Ankle Score (AOFAS) (p = .003) and a decrease in the average Visual Analogue Scale pain score (p = .003). There was no statistically significant decrease in ROM before or after surgery (p = .114). Additionally, no talus collapse of the ankle joint occurred. Talar dome status did not aggravate before or after surgery, except for one patient. Despite no radiographic osteoarthritis exacerbation before or after surgery in six patients, five patients had osteoarthritic change. CONCLUSION: Cement implantation and autologous bone graft performed simultaneously for benign bone tumors with joint cartilage damage and AVN are technically simple, have good outcomes, and may be a suitable alternative to standard treatments.

NY-ESO-1 as a diagnostic and prognostic marker for myxoid liposarcoma.

INTRODUCTION: Myxoid liposarcoma (MLS) is a common lipogenic sarcoma, which is difficult to diagnose in small specimens. New York oesophageal squamous cell carcinoma 1 (NY-ESO-1) is a cancer-testis antigen expressed in neoplastic tissue. In this study, NY-ESO-1 expression was assessed in various soft tissue tumors (STTs), and we also evaluated its diagnostic utility. METHODS: We included 434 cases of STTs for collection of clinicopathological data. Tissue microarrays were designed, and immunostaining for NY-ESO-1 was examined. We investigated the correlation between NY-ESO-1 expression and various clinicopathological parameters. We also evaluated the role of NY-ESO-1 as a diagnostic marker for MLS and its possible use in prognostication. RESULTS: Sixty-four of the 434 STTs (14.75%) were immunoreactive for NY-ESO-1, and the most frequent type of tumor in the NY-ESO-1 positive group was MLS (70.3%, 45/64), followed by synovial sarcoma (17.2%, 11/64). MLS showed 72.6% (45/62) immunopositivity for NY-ESO-1. The sensitivity and specificity of NY-ESO-1 expression for the diagnosis of MLS were 84.4% and 100%, respectively, compared to DDIT3 fluorescence in situ hybridization. When restricting analysis to the MLS (n=62), the NY-ESO-1 positive group had a poor overall survival (OS) rate (P=0.039). CONCLUSION: NY-ESO-1 was substantially and widely expressed in the majority of MLS cases. NY-ESO-1 positivity by IHC staining was also a predictor of a poor OS in patients with MLS. It is possible to use NY-ESO-1 for diagnosis and for predicting a prognosis in patients with MLS, and it may be used as a therapeutic target.

Distinct histologic and genetic characteristics of round cell sarcoma with CIC-DUX4 fusion and comparison with ewing sarcoma.

CIC-DUX4 fusion gene associated sarcoma is a new emerging subgroup of round cell sarcoma with Ewing sarcoma-like morphology. Distinguishing these tumors from Ewing sarcoma family tumors (ESFT) is critical because of the clinical impact but is still challenging due to the overlapped histological and immunohistochemical phenotypes of each subtype. The present study investigated small round cell sarcoma to identify CIC-DUX4 fusion positive sarcoma, examined clinical, histopathologic and immunohistochemical characteristics of CIC-DUX4 sarcoma, and evaluated parameters to differentiate Ewing sarcoma family tumors. Seventy patients with undifferentiated round cell sarcoma or Ewing-like sarcoma were retrieved. Molecular tests including EWSR1, CIC break apart FISH, and RT-PCR for CIC-DUX4 gene fusion were performed and immunohistochemistry was performed. Six cases (8.6%) of CIC-DUX4 sarcomas were detected. Histologically, CIC-DUX4 sarcomas composed of heterogeneous round, plasmacytoid, and spindle cells and more commonly showed cytologic pleomorphism with bizarre nuclei and multinucleated cells and myxoid stoma unlike ESFT. CIC-DUX4 sarcomas didn't show overall survival differences (p = 0.325) compared to ESFT but they demonstrated short disease-free survival (p = 0.034) and poor response to treatment (p = 0.007). Therefore, molecular analysis to detect the distinctive genetic alteration is mandatory in tumors with atypical histologic, immunohistochemical and/or clinical presentation for accurate diagnosis and treatment.

Clinicopathologic Characteristics and Clinical Outcome of Localized Liposarcoma: A Single-Center Experience over 25 Years and Evaluation of PD-L1 Expression.

PURPOSE: For liposarcoma (LPS), clinical course and proper treatment strategies have not been well-established. Recently, immune-checkpoint inhibitors have shown potential efficacy in LPS. We aimed to describe the clinical course of LPS and evaluate the clinical impact of programmed death-ligand 1 (PD-L1). MATERIALS AND METHODS: We reviewed all consecutive patients (n=332) who underwent curative-intent surgery for localized LPS at Asan Medical Center between 1989 and 2017. PD-L1 testing was performed in well-differentiated and dedifferentiated LPS. RESULTS: The median age was 56 years with males comprising 60.8%. Abdomen-pelvis (47.6%) and well-differentiated (37.7%) were the most frequent primary site and histologic subtype, respectively. During a median follow-up of 81.2 months, recurrence was observed in 135 (40.7%), and 86.7% (117/135) were loco-regional. Well-differentiated subtype (hazard ratio [HR], 0.38), abdomen-pelvis origin (HR, 2.43), tumor size larger than 5 cm (HR, 1.83), positive resection margin (HR, 2.58), and postoperative radiotherapy (HR, 0.36) were significantly related with recurrence-free survival as well as visceral involvement (HR, 1.84) and multifocality (HR, 3.79) in abdomen-pelvis LPS. PD-L1 was positive in 31.5% (23/73) and 51.3% (39/76) of well-differentiated and dedifferentiated LPS, respectively, but had no impact on survival outcomes. CONCLUSION: Clinical course of LPS was heterogeneous according to histology and anatomic location. Clear resection margin was important to lower recurrence and postoperative radiotherapy might have additional benefit. A decent portion of well-differentiated and dedifferentiated LPS were positive for PD-L1, but its prognostic role was unclear. Further research is needed to determine clinical implications of PD-L1, especially for advanced-stage LPS with unmet needs for effective systemic treatment.

Integrin αvß3 Induces HSP90 Inhibitor Resistance via FAK Activation in KRAS-Mutant Non-Small Cell Lung Cancer.

PURPOSE: Heat shock protein-90 (HSP90) remains an important cancer target because of its involvement in multiple oncogenic protein pathways and biologic processes. Although many HSP90 inhibitors have been tested in the treatment of KRAS-mutant non-small cell lung cancer (NSCLC), most, including AUY922, have failed due to toxic effects and resistance generation, even though a modest efficacy has been observed for these drugs in clinical trials. In our present study, we investigated the novel mechanism of resistance to AUY922 to explore possible avenues of overcoming and want to provide some insights that may assist with the future development of successful next-generation HSP90 inhibitors. MATERIALS AND METHODS: We established two AUY922-resistant KRAS-mutated NSCLC cells and conducted RNA sequencing to identify novel resistance biomarker. RESULTS: We identified novel two resistance biomarkers. We observed that both integrin Av (ITGAv) and ß3 (ITGB3) induce AUY922-resistance via focal adhesion kinase (FAK) activation, as well as an epithelial-mesenchymal transition, in both in vitro and in vivo xenograft model. mRNAs of both ITGAv and ITGB3 were also found to be elevated in a patient who had shown acquired resistance in a clinical trial of AUY922. ITGAv was induced by miR-142 downregulation, and ITGB3 was increased by miR-150 downregulation during the development of AUY922-resistance. Therefore, miR-150 and miR-142 overexpression effectively inhibited ITGAvB3-dependent FAK activation, restoring sensitivity to AUY922. CONCLUSION: The synergistic co-targeting of FAK and HSP90 attenuated the growth of ITGAvB3-induced AUY922-resistant KRAS-mutated NSCLC cells in vitro and in vivo, suggesting that this combination may overcome acquired AUY922-resistance in KRAS-mutant NSCLC.

Demographics, Changes in Treatment Patterns, and Outcomes of Bone and Soft Tissue Sarcomas in Korea-A Sarcoma-Specific, Institutional Registry-Based Analysis.

PURPOSE: Because of the heterogeneity of sarcomas, establishing a well-collected, sarcoma-specific database is important for sarcoma research. We analyzed the first histology-based, sarcoma-specific institutional registry in Korea, which collected 28 years of patient data according to a predefined data format. PATIENTS AND METHODS: Adult bone and soft tissue sarcoma patients who were treated from June 1989 to January 2017 were identified and analyzed, based on the ICD-O-3 codes. RESULTS: Among the 3420 patients included, soft tissue and bone sarcomas comprised 77.8% (n = 2661) and 22.2% (n = 759), respectively. Median age at diagnosis was 50 (range, 16-98) in soft tissue sarcomas and 37 (range, 16-85) in bone sarcomas. Males and females comprised 45.5% and 54.5% of soft tissue sarcomas and 52.7% and 47.3% of bone sarcomas, respectively. Among the 3407 patients with treatment data available, 90.5% of the patients with soft tissue sarcomas and 80.8% of the patients with bone sarcomas received surgery first, of which 57.8% and 71.7% did not receive any subsequent treatment, respectively. Overall, the proportion of patients who received surgery alone decreased from 85.7% to 60.5% from the pre-2000 period to the 2010-2017 period. However, the use of adjuvant chemotherapy increased in patients with soft tissue sarcomas (from 8.0% to 17.2% in the same period), and the use of perioperative radiotherapy also increased in both groups (from 1.4% to 22.7% in soft tissue sarcomas, and 0% to 14.5% in bone sarcomas in the same period). In both soft tissue and bone sarcomas, old age (≥65 years) and diagnosis in the early study period were associated with poorer survival. CONCLUSION: We presented a comprehensive summary of our sarcoma registry, including the demographics, changes in treatment patterns, and survival outcomes. This study will provide a framework for future studies.

Undervaluation of Radiotherapy for Gross Desmoid Tumors: The Need for Absolute Volume Assessment.

BACKGROUND/AIM: To compare absolute volume (AV) assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) for the response evaluation of desmoid tumors (DTs) treated with radiotherapy. PATIENTS AND METHODS: Eighteen patients with DTs ≥3 cm in size were included. RESULTS: The median follow-up duration was 78.0 months. Five patients achieved a complete response according to RECIST, seven reached a partial response (PR), and one eventually exhibited progression. The overall response rate was 61%, the median time to PR was 8.0 months. Six patients achieved stable disease, although three developed progressions. Of the six patients with a PR, the median change in maximum diameter was -46%, and the median change in maximum volume was -84%. Three patients could have been diagnosed with progression at least 6 months earlier if the AV increment was considered. CONCLUSION: An AV assessment is essential for an accurate response assessment of DTs and radiotherapy seems feasible as a first-line treatment for DTs.

Differences between 3D isovoxel fat suppression VIBE MRI and CT models of proximal femur osseous anatomy: A preliminary study for bone tumor resection planning.

PURPOSE: To evaluate the osseous anatomy of the proximal femur extracted from a 3D-MRI volumetric interpolated breath-hold (VIBE) sequence using either a Dixon or water excitation (WE) fat suppression method, and to measure the overall difference using CT as a reference standard. MATERIAL AND METHODS: This retrospective study reviewed imaging of adult patients with hip pain who underwent 3D hip MRI and CT. A semi-automatically segmented CT model served as the reference standard, and MRI segmentation was performed manually for each unilateral hip joint. The differences between Dixon-VIBE-3D-MRI vs. CT, and WE-VIBE-3D-MRI vs. CT, were measured. Equivalence tests between Dixon-VIBE and WE-VIBE models were performed with a threshold of 0.1 mm. Bland-Altman plots and Lin's concordance-correlation coefficient were used to analyze the agreement between WE and Dixon sequences. Subgroup analyses were performed for the femoral head/neck, intertrochanteric, and femoral shaft areas. RESULTS: The mean and maximum differences between Dixon-VIBE-3D-MRI vs. CT were 0.2917 and 3.4908 mm, respectively, whereas for WE-VIBE-3D-MRI vs. CT they were 0.3162 and 3.1599 mm. The mean differences of the WE and Dixon methods were equivalent (P = 0.0292). However, the maximum difference was not equivalent between the two methods and it was higher in WE method. Lin's concordance-correlation coefficient showed poor agreement between Dixon and WE methods. The mean differences between the CT and 3D-MRI models were significantly higher in the femoral shaft area (P = 0.0004 for WE and P = 0.0015 for Dixon) than in the other areas. The maximum difference was greatest in the intertrochanteric area for both techniques. CONCLUSION: The difference between 3D-MR and CT models were acceptable with a maximal difference below 3.5mm. WE and Dixon fat suppression methods were equivalent. The mean difference was highest at the femoral shaft area, which was off-center from the magnetization field.

Usefulness of 68Ga-DOTATOC PET/CT to localize the culprit tumor inducing osteomalacia.

Tumor-induced osteomalacia (TIO) is an uncommon paraneoplastic syndrome presenting with sustained hypophosphatemia. Treatment of choice is removal of the tumor causing the TIO, but identification of the culprit tumor by routine imaging is challenging. This study aimed to assess the usefulness of somatostatin receptor imaging, called 68Ga-DOTATOC PET/CT, in the management of patients with TIO. Twelve patients who were suspected of having TIO underwent 68Ga-DOTATOC PET/CT. Lesion detectability and maximum standardized uptake value (SUVmax) were determined and retrospectively compared with the clinical/imaging surveillance and histopathologic diagnosis. The median duration of suspected TIO with hypophosphatemia was 7.8 years (range 2.1-21.0). Conventional radiologic and/or nuclear medicine images failed to identify the culprit tumors. However, 68Ga-DOTATOC PET/CT scans showed that 8 of the 12 patients had positive lesions, suggesting the presence of focal culprit tumors. The SUVmax of positive tumors was 1.9-45.7 (median: 11.5). Six skeletal lesions and two extra-skeletal lesions were identified. Seven of the lesions were pathologically confirmed as potential culprits of TIO. Hypophosphatemia was resolved in five patients who underwent lesion excision. The 68Ga-DOTATOC PET/CT is a useful whole-body imaging modality for the detection of causative tumors in patients with suspected TIO.

Pathological fractures of the femur after radiation therapy for soft tissue tumor: a case series of seven patients treated with repeated internal fixation.

INTRODUCTION: Pathological femoral fracture (PFF) after radiation therapy (RT) for soft tissue tumor is a debilitating complication with a high rate of nonunion that requires multiple subsequent procedures and hindrance of functional activity. We aimed to evaluate healing rate after repeated internal fixation in a case series of PFF after RT. MATERIALS AND METHODS: We retrospectively reviewed the records of patients who had PFF after RT and were treated at our center between 2007 and 2018. We analyzed our surgical protocols and fracture healing rate. INTERPRETATION: We identified and analyzed a total of seven patients (six females and one male) whose mean age at fracture was 58 years. Primary tumors consisted of soft tissue sarcoma (n = 5), melanoma (n = 1), and desmoid tumor (n = 1). All primary tumors were treated with surgical excision and adjuvant RT. The mean follow-up duration after fracture was 33 months (range, 16-58). At the last follow-up, five out of seven fractures had completely healed, and two lesions showed delayed union at 15 and 16 months, respectively. Among the five complete unions, one fracture was healed after the first fixation. The remaining four lesions were treated with second internal fixation due to nonunion/metal failure or delayed union. The mean time to radiologic healing after the last fixation was 6.8 months (range, 5-8). CONCLUSIONS: Our results suggest that bones within the RT field retain healing capacities, and that repeated internal fixation may be a viable option for the treatment of PFF after RT.

Blockade of CCL2 expression overcomes intrinsic PD-1/PD-L1 inhibitor-resistance in transglutaminase 2-induced PD-L1 positive triple negative breast cancer.

Anti-PD-1/PD-L1 immunotherapy, as a treatment for many tumors, has shown good efficacy. However, responses to immunotherapy did not always occur or last long., i.e. primary or acquired resistance, even tumors were PD-L1 positive. Several oncogenic pathways, including PI3K/AKT activation by PTEN loss and NF-κB activation, induce PD-L1 expression and PD-L1 inhibitor-resistance. They also induce expression of CCL2, an inhibitory chemokine that blocks T cell tracking into the tumor by binding to CCR2 on the T cell surface. In this study, we showed that transglutaminase 2 (TG2), a post-translational modification enzyme, induced ubiquitin-proteasome dependent degradation of tumor suppressors including PTEN and IκBα by peptide cross-linking, inducing CCL2 as well as PD-L1 expression via PI3K/AKT and NF-κB activation. It also induced PD-L1 inhibitor-resistance because CCL2 was expressed despite increased PD-L1, which was blocked by PD-L1 inhibitor. We also revealed that inhibition of TG2, instead of PD-L1, restored T cell-dependent killing effect by blocking expression of both PD-L1 and CCL2 in PD-L1(+) triple negative breast cancer (TNBC) cells. In addition, the TG2-expressing TNBC patient group showed higher PD-L1 expression incidence than did the TG2-negative TNBC patient group. In conclusion, TG2 induces primary PD-1/PD-L1 inhibitor-resistance by inducing CCL2 expression. TG2 blockade can be utilized as an excellent therapeutic strategy to overcome PD-L1 inhibitor-resistance in PD-L1(+) TNBC patients. Our study suggested that PD-L1 expression alone might not always be a predictive biomarker for PD-L1(+) TNBC, but TG2 could be a useful predictive marker to select PD-L1 inhibitor-resistant TNBC patients.

Oncologic safety of propeller flap and free flap in reconstruction after soft tissue sarcoma resection.

BACKGROUND AND OBJECTIVES: The propeller flap is a reliable option for reconstruction after soft tissue sarcoma resection. However, some parts of the resection margin may move away from its original position during flap rotation and thus can be excluded from the clinical target volume of adjuvant radiotherapy. This study aimed to evaluate local recurrence after soft tissue sarcoma resection with propeller flap or free flap reconstruction. METHODS: Patients who underwent resection of soft tissue sarcoma followed by a free flap or propeller flap reconstruction and adjuvant radiotherapy at a single institution were retrospectively reviewed. RESULTS: The 1- and 3-year local control rates were 94.6% and 88.6% in the free flap group vs 90.6% and 87.5% in the propeller flap group, without statistical significance. There were no statistically significant differences in 5-year local recurrence-free survival (88.6% vs 87.5%) and disease-free survival (82.5% vs 74.8%) between the groups. CONCLUSIONS: Although there was no significant difference in local control and disease-free survival rates between propeller flap and free flap reconstruction after soft tissue sarcoma resection, a multidisciplinary approach is needed to obtain surgical information for determining the accurate clinical target volume of adjuvant radiotherapy and the area for meticulous follow-up postoperatively.

The clinical outcomes of undifferentiated pleomorphic sarcoma (UPS): A single-centre experience of two decades with the assessment of PD-L1 expressions.

INTRODUCTION: Little is known about undifferentiated pleomorphic sarcoma (UPS) because of the low incidence and heterogeneous diagnosis of sarcoma. We investigated the oncologic outcomes of patients with UPS in a real-practice setting in association with adjuvant treatments and assessment of PD-L1 expression. MATERIALS AND METHODS: We retrospectively reviewed consecutive patients who were diagnosed with UPS in Asan Medical Center between January 1995 and December 2016. PD-L1 staining was performed using formalin-fixed paraffin-embedded tumour tissue by immunohistochemistry, and positive PD-L1 expression was defined as staining in ≥1% of tumour cells. The PD-L1 H-score, which was calculated for statistical analysis as intensity (0-3) multiplied by proportion (0-100), ranged from 0 to 300. RESULTS: Of 205 patients included in our analysis, 176 underwent a curative-intent operation for localised disease. The five-year disease-free survival (DFS) rate of resected UPS patients was 54.3%. Administration of adjuvant therapy did not overcome the poor prognostic factors such as primary tumour size (>5 cm) and locations, especially the abdomen and pelvis. The PD-L1 analysis was available for 114 patients, and 83 (72.8%) showed immunoreactivity for PD-L1 with weak (44/83), intermediate (29/83), and strong (10/83) staining intensities. The positive PD-L1 expression seemed to be associated with prolonged DFS, though no statistical significance was observed. CONCLUSION: Complete surgical resection was the most important UPS treatment strategy, and adjuvant radio- or chemotherapy was insufficient to improve survival. Our results raise the possibility that immunotherapy could be a breakthrough in the treatment of UPS patients.

Bone oxaloma-a localized manifestation of bone oxalosis.

Oxalosis is a metabolic disorder characterized by the accumulation of calcium oxalate deposits in various organ systems. Bone oxalosis is a systemic manifestation of oxalosis, in which calcium oxalate deposits accumulate in the skeletal system. This report describes a 69-year-old female patient who presented with right hip pain and was later found to have an osseous mass-like lesion in the right proximal femur, with radiographic findings resembling those of a benign bone tumor. CT-guided biopsy and surgical biopsy showed that the mass had pathologic findings typical of bone oxalosis. Because the patient had no predisposing factors for systemic oxalosis and had no hyperoxalemia or hyperoxaluria, she could be diagnosed with localized bone oxalate deposition disease or bone oxaloma rather than bone oxalosis. This is the first report of this clinical entity to present as a benign-appearing bone mass and without any predisposing systemic causes.