Enhancing radiotherapy response via intratumoral injection of a TLR9 agonist in autochthonous murine sarcomas.

Radiation therapy (RT) is frequently used to treat cancers, including soft-tissue sarcomas. Prior studies established that the toll-like receptor 9 (TLR9) agonist cytosine-phosphate-guanine oligodeoxynucleotide (CpG) enhances the response to RT in transplanted tumors, but the mechanisms of this enhancement remain unclear. Here, we used CRISPR/Cas9 and the chemical carcinogen 3-methylcholanthrene (MCA) to generate autochthonous soft-tissue sarcomas with high tumor mutation burden. Treatment with a single fraction of 20 Gy RT and 2 doses of CpG significantly enhanced tumor response, which was abrogated by genetic or immunodepletion of CD8+ T cells. To characterize the immune response to CpG+RT, we performed bulk RNA-Seq, single-cell RNA-Seq, and mass cytometry. Sarcomas treated with 20 Gy and CpG demonstrated increased CD8 T cells expressing markers associated with activation and proliferation, such as Granzyme B, Ki-67, and IFN-γ. CpG+RT also upregulated antigen presentation pathways on myeloid cells. Furthermore, in sarcomas treated with CpG+RT, TCR clonality analysis suggests an increase in clonal T cell dominance. Collectively, these findings demonstrate that CpG+RT significantly delays tumor growth in a CD8 T cell-dependent manner. These results provide a strong rationale for clinical trials evaluating CpG or other TLR9 agonists with RT in patients with soft-tissue sarcoma.

Mapping the Course of Recovery Following Limb-Salvage Surgery for Soft-Tissue Sarcoma of the Extremities.

BACKGROUND: Despite the goal of an acceptable functional result, the surgical treatment of soft-tissue sarcoma can portend a prolonged course of recovery. More comprehensive data on the expected course of recovery following extremity sarcoma surgery are needed to help to inform physicians and patients. The purpose of the present study was to describe the typical course of functional recovery following limb-salvage resection of a soft-tissue sarcoma and to identify factors associated with a delayed postoperative course of recovery. METHODS: A retrospective review of a prospectively maintained institutional database was performed for all patients undergoing surgical treatment with limb salvage of a soft-tissue sarcoma of the extremities or pelvis with at least 1 year of follow-up after the definitive surgical procedure. All patients were required to have preoperative functional outcomes recorded for either the Toronto Extremity Salvage Score (TESS) or the Musculoskeletal Tumor Society (MSTS) score and functional outcome measures at 1 year postoperatively. The primary outcome measures were time to recovery and maximal functional improvement. RESULTS: In this study, 916 patients met inclusion criteria following surgical resection of a soft-tissue sarcoma of the extremities. The median follow-up was 74 months. Patients typically achieved a return to their baseline preoperative level of function for all functional outcome measures by 1 to 2 years and achieved maximal functional recovery by 2 years postoperatively. Older age, female sex, deep tumor location, larger tumor size, pelvic location, osseous resection, motor nerve resection, free and/or rotational soft-tissue coverage, and postoperative complications were independently associated with worse TESS and/or MSTS scores (p ≤ 0.05). Tumor recurrence was associated with worse functional outcomes scores. An analysis was performed to determine which patients had a prolonged course of recovery (i.e., were considered to still be recovering). Older age, female sex, larger tumor size, osseous resection, and motor nerve resection were associated with a delayed course of recovery (p ≤ 0.04). Complications and tumor recurrence were associated with delayed functional recovery across all domains. CONCLUSIONS: Most patients will achieve maximal recovery by 2 to 3 years following surgical resection for soft-tissue sarcoma of the extremities. Older age, female sex, larger tumor size, osseous resection, motor nerve resection, postoperative complications, and tumor recurrence portend poorer functional outcomes and a delayed course of recovery. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Management of bone disease with concurrent chimeric antigen receptor T-cell therapy for multiple myeloma.

In the intricate landscape of multiple myeloma, a hematologic malignancy of plasma cells, bone disease presents a pivotal and often debilitating complication. The emergence of Chimeric Antigen Receptor T-cell (CAR-T) therapy has marked a pivotal shift in the therapeutic landscape, offering novel avenues for the management of MM, particularly for those with relapsed or refractory disease. This innovative treatment modality not only targets malignant cells with precision but also influences the bone microenvironment, presenting both challenges and opportunities in patient care. In this comprehensive review, we aim to examine the multifaceted aspects of bone disease in patients with multiple myeloma and concurrent CAR-T therapy, highlighting its clinical ramifications and the latest advancements in diagnostic modalities and therapeutic interventions. The article aims to synthesize current understanding of the interplay between myeloma cells, CAR-T cells, and the bone microenvironment in the context of current treatment strategies in this challenging and unique patient population.

Enhancing radiotherapy response via intratumoral injection of the TLR9 agonist CpG to stimulate CD8 T cells in an autochthonous mouse model of sarcoma.

Radiation therapy is frequently used to treat cancers including soft tissue sarcomas. Prior studies established that the toll-like receptor 9 (TLR9) agonist cytosine-phosphate-guanine oligodeoxynucleotide (CpG) enhances the response to radiation therapy (RT) in transplanted tumors, but the mechanism(s) remain unclear. Here, we used CRISPR/Cas9 and the chemical carcinogen 3-methylcholanthrene (MCA) to generate autochthonous soft tissue sarcomas with high tumor mutation burden. Treatment with a single fraction of 20 Gy RT and two doses of CpG significantly enhanced tumor response, which was abrogated by genetic or immunodepletion of CD8+ T cells. To characterize the immune response to RT + CpG, we performed bulk RNA-seq, single-cell RNA-seq, and mass cytometry. Sarcomas treated with 20 Gy and CpG demonstrated increased CD8 T cells expressing markers associated with activation and proliferation, such as Granzyme B, Ki-67, and interferon-γ. CpG + RT also upregulated antigen presentation pathways on myeloid cells. Furthermore, in sarcomas treated with CpG + RT, TCR clonality analysis suggests an increase in clonal T-cell dominance. Collectively, these findings demonstrate that RT + CpG significantly delays tumor growth in a CD8 T cell-dependent manner. These results provide a strong rationale for clinical trials evaluating CpG or other TLR9 agonists with RT in patients with soft tissue sarcoma.

Limb Amputations in Cancer: Modern Perspectives, Outcomes, and Alternatives.

PURPOSE OF REVIEW: This review summarizes current findings regarding limb amputation within the context of cancer, especially in osteosarcomas and other bony malignancies. We seek to answer the question of how amputation is utilized in the contemporary management of cancer as well as explore current advances in limb-sparing techniques. RECENT FINDINGS: The latest research on amputation has been sparse given its extensive history and application. However, new research has shown that rotationplasty, osseointegration, targeted muscle reinnervation (TMR), and regenerative peripheral nerve interfaces (RPNI) can provide patients with better functional outcomes than traditional amputation. While limb-sparing surgeries are the mainstay for managing musculoskeletal malignancies, limb amputation is useful as a palliative technique or as a primary treatment modality for more complex cancers. Currently, rotationplasty and osseointegration have been valuable limb-sparing techniques with osseointegration continuing to develop in recent years. TMR and RPNI have also been of interest in the modern management of patients requiring full or partial amputations, allowing for better control over myoelectric prostheses.

Open Versus Core Needle Biopsy in Lower-Extremity Sarcoma: Current Practice Patterns and Patient Outcomes.

BACKGROUND: Historically, open biopsy (OB) was the gold standard for sarcoma diagnosis. Core needle biopsy (CNB) has become increasingly common. There are limited data evaluating how the type of biopsy impacts definitive surgical resection or postoperative outcomes. The aims of this study were to (1) characterize current international biopsy practice patterns, and (2) evaluate how the type of biopsy performed impacts the resection surgery, infection risk, oncological complications, and patient-reported functional outcome scores. METHODS: This study was a preplanned secondary analysis of the prospective, multicenter PARITY (Prophylactic Antibiotic Regimens in Tumor Surgery) study. Patients with a benign diagnosis, metastatic disease, or no biopsy prior to surgery were excluded. Prospectively collected demographic, biopsy, surgical, and outcome variables were analyzed, and differences between patients undergoing OB and CNB were assessed. Parametric and nonparametric tests were used to compare variables between groups, and the Cox proportional hazards method was used to compare infection-related and oncological outcomes at 1 year. Median functional outcome scores at 1 year were compared. RESULTS: Four hundred and sixty-four patients met the inclusion criteria. Data were collected from 48 sarcoma centers in 12 countries. CNB was the more utilized biopsy modality overall (57.5%). OB was more common in the U.S. and Canada. The median operative time was significantly longer for patients who underwent OB (324 versus 260 minutes; p < 0.001). Significantly more skin (p < 0.001) and fascial tissue (p < 0.001) were excised in the OB group, which also had a lower rate of primary closure (86.3% versus 92.9%; p = 0.03). There were no differences in surgical site infection or oncological outcomes between the groups at 1-year follow-up. CONCLUSIONS: CNB was the more common biopsy modality in the PARITY study in most countries. However, OB was more common in the U.S. and Canada. Patients undergoing OB had longer operative times, more excised tissue, and lower rates of primary closure, but this did not translate to differences in infection rates or oncological outcomes, including local recurrence. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Tumor necrosis is an underappreciated histopathologic factor in the grading of chondrosarcoma.

BACKGROUND: Cartilaginous neoplasms can be challenging to grade; there is a need to create an evidence-based rubric for grading. The goal of this study was to identify histopathologic features of chondrosarcoma that were associated with 5-year survival and to compare these to traditional patient, tumor and treatment variables. METHODS: This was a retrospective review of all patients undergoing surgical resection of a primary chondrosarcoma with at least 2 years of follow up. All specimens were independently reviewed by two pathologists and histopathologic features scored. Univariate and multivariate analyses were performed utilizing Kaplan Meier and proportional hazards methods to identify variables associated with 5-year disease specific survival (DSS) and disease free survival (DFS). RESULTS: We identified 51 patients with an average follow up of 49 months eligible for inclusion. 30% of tumors were low grade, 45% were intermediate grade, and 25% were high grade. In a univariate analysis considering histopathologic factors, higher tumor mitotic rate (HR 8.9, p < 0.001), tumor dedifferentiation (HR 7.3, p < 0.001), increased tumor cellularity (HR 5.8, p = 0.001), increased tumor atypia (HR 5.8, p = 0.001), LVI (HR 4.7, p = 0.04) and higher tumor necrosis (HR 3.7, p = 0.02) were all associated with worse 5-year DSS. In a multivariate analysis controlling for potentially confounding variables, higher tumor necrosis was significantly associated with disease specific survival survival (HR 3.58, p = 0.035); none of the factors were associated with DFS. CONCLUSIONS: This study provides an evidence-based means for considering histopathologic markers and their association with prognosis in chondrosarcoma. Our findings suggest that necrosis and LVI warrant further study.

Is a radiological score able to predict resection-grade chondrosarcoma in primary intraosseous lesions of the long bones?

Aims: The preoperative grading of chondrosarcomas of bone that accurately predicts surgical management is difficult for surgeons, radiologists, and pathologists. There are often discrepancies in grade between the initial biopsy and the final histology. Recent advances in the use of imaging methods have shown promise in the ability to predict the final grade. The most important clinical distinction is between grade 1 chondrosarcomas, which are amenable to curettage, and resection-grade chondrosarcomas (grade 2 and 3) which require en bloc resection. The aim of this study was to evaluate the use of a Radiological Aggressiveness Score (RAS) to predict the grade of primary chondrosarcomas in long bones and thus to guide management. Methods: A total of 113 patients with a primary chondrosarcoma of a long bone presenting between January 2001 and December 2021 were identified on retrospective review of a single oncology centre's prospectively collected database. The nine-parameter RAS included variables from radiographs and MRI scans. The best cut-off of parameters to predict the final grade of chondrosarcoma after resection was determined using a receiver operating characteristic curve (ROC), and this was correlated with the biopsy grade. Results: A RAS of ≥ four parameters was 97.9% sensitive and 90.5% specific in predicting resection-grade chondrosarcoma based on a ROC cut-off derived using the Youden index. Cronbach's α of 0.897 was derived as the interclass correlation for scoring the lesions by four blinded reviewers who were surgeons. Concordance between resection-grade lesions predicted from the RAS and ROC cut-off with the final grade after resection was 96.46%. Concordance between the biopsy grade and the final grade was 63.8%. However, when the patients were analyzed based on surgical management, the initial biopsy was able to differentiate low-grade from resection-grade chondrosarcomas in 82.9% of biopsies. Conclusion: These findings suggest that the RAS is an accurate method for guiding the surgical management of patients with these tumours, particularly when the initial biopsy results are discordant with the clinical presentation.

Regional anesthesia is associated with improved metastasis free survival after surgical resection of bone sarcomas.

There is increasing evidence that perioperative factors, including type of anesthesia, may be an important consideration regarding oncological disease progression. Previous studies have suggested that regional anesthesia can improve oncological outcomes by reducing the surgical stress response that occurs during tumor resection surgery and that may promote metastatic progression. The purpose of this study is to provide the first robust investigation of the impact of adding regional anesthesia to general anesthesia on oncological outcomes following sarcoma resection. One hundred patients with bone sarcoma were retrospectively analyzed in this study. After adjusting for confounding variables such as age and grade of the tumor, patients with bone sarcoma receiving regional anesthesia in addition to general anesthesia during resection had improved metastasis free survival (multivariate hazard ratio of 0.47 and p = 0.034). Future studies are needed to confer the beneficial effect of regional anesthesia, and to further investigate the potential mechanism. Clinical significance: The results from this study provide evidence that regional anesthesia may be advantageous in the setting of bone sarcoma resection surgery, reducing pain while also improving oncological outcomes and should be considered when clinically appropriate.

Atrx deletion impairs CGAS/STING signaling and increases sarcoma response to radiation and oncolytic herpesvirus.

ATRX is one of the most frequently altered genes in solid tumors, and mutation is especially frequent in soft tissue sarcomas. However, the role of ATRX in tumor development and response to cancer therapies remains poorly understood. Here, we developed a primary mouse model of soft tissue sarcoma and showed that Atrx-deleted tumors were more sensitive to radiation therapy and to oncolytic herpesvirus. In the absence of Atrx, irradiated sarcomas had increased persistent DNA damage, telomere dysfunction, and mitotic catastrophe. Our work also showed that Atrx deletion resulted in downregulation of the CGAS/STING signaling pathway at multiple points in the pathway and was not driven by mutations or transcriptional downregulation of the CGAS/STING pathway components. We found that both human and mouse models of Atrx-deleted sarcoma had a reduced adaptive immune response, markedly impaired CGAS/STING signaling, and increased sensitivity to TVEC, an oncolytic herpesvirus that is currently FDA approved for the treatment of aggressive melanomas. Translation of these results to patients with ATRX-mutant cancers could enable genomically guided cancer therapy approaches to improve patient outcomes.

Reconstructive Allograft Preparation for Long Bone Intercalary Segments After Tumor Resections: Toronto Sarcoma Protocol.

Background: The Reconstructive Allograft Preparation by Toronto Sarcoma (RAPTORS) protocol is reliable and reproducible without substantially adding to the surgical reconstruction time or cost. Our technique includes clearance of debris, lavage of the medullary canal, pressurized filling of the medullary canal with antibiotic-laden cement for its mechanical and antimicrobial properties, and insertion of cancellous autograft at the allograft-host junctional ends prior to dual-plate compression to fix the allograft into the defect1-3. Our experience with large intercalary allograft reconstruction has demonstrated high rates of long-term success and addresses the most common causes of large allograft failure (infection, fracture, and nonunion)4, as shown in our long-term outcome study1. Description: Once the tumor is resected, it is used as a template for cutting and shaping the allograft to fit the bone defect and to restore length and anatomy. The frozen allograft is thawed in a container with povidone iodine and bacitracin saline solution until it reaches room temperature. The allograft is size-matched, and clearance of its intramedullary marrow contents is performed with use of curets and intramedullary reamers7. If 1 end of the allograft includes the metaphysis and is covered by dense cancellous bone, we try not to ream through this end because maintaining this metaphyseal cancellous surface will expedite bone healing. The segment is then thoroughly lavaged with "triple wash" solutions to clear out any remaining marrow contents and to ensure sterilization of the allograft. This serial-wash technique involves the use of 3 discrete antiseptic modalities and has been utilized at our institution with low rates of allograft infection. These antiseptic modalities include 10% weight-per-volume povidone iodine diluted 1:1 with normal saline solution, 3% weight-per-volume hydrogen peroxide diluted 1:1 with normal saline solution, and 50,000 units of sterile bacitracin lyophilized powder dissolved in 500 mL of normal saline solution. Following the triple wash, the medullary canal is filled with antibiotic-laden methylmethacrylate bone cement. If both ends are open, the far end of the segment is first plugged with the surgeon's finger or with gauze, or if 1 end is covered with cancellous bone, then retrograde filling of the canal with cement is performed from the open end. The cement is then pressurized to ensure complete filling of the intramedullary space. Before it sets, 1 cm of cement is removed from each open end of the allograft to allow for packing of autograft bone cancellous chips and to ensure that cement does not impede anatomic reduction of the allograft-host bone junction. For this step, cancellous autograft from the iliac crest is harvested with use of a separate sterile surgical setup in order to prevent contamination of the autograft site by instruments used for tumor resection. The cancellous autograft is packed into the space created after recessing the cement at the end(s) of the allograft and, using a bone tamp, the autograft is compressed into this cavity and into the corresponding end of the host long bone in order to improve the healing potential at the allograft-host bone junction(s)8. Finally, a dual compression plate construct is utilized for upper as well as lower-extremity reconstructions in most cases. The cement in the allograft must be completely hardened before drilling into it. The allograft-host bone junctions are sequentially compressed at both the proximal and distal ends to allow for maximal apposition of the osseous surfaces. Only 1 or 2 unicortical screws are placed into the allograft to hold it in place and to facilitate maximal compression at both bone junctions. Patient compliance during postoperative rehabilitation is essential to optimize healing and provide reliable and durable outcomes. Postoperative care following the RAPTORS technique includes limited early rehabilitation and long periods of non-weight-bearing until radiographic union is noted across both bone junctions, followed by gradual resumption of weight-bearing and more aggressive physiotherapy. See the Appendix for further details regarding each step of the procedure. Alternatives: Intercalary reconstruction alternatives include various biological or endoprosthetic constructs. The other biological reconstruction options include the use of a free vascularized bone graft, distraction osteogenesis, combined vascularized fibula and allograft (i.e., the Capanna technique), or recycled tumor bones. Intercalary prostheses offer another reconstruction option for diaphyseal defects, but their feasibility is more limited in cases of periarticular segments with very short residual medullary canals. In such cases, there may be inadequate stem length for fixation, or the segment may require a custom implant that takes time to design and manufacture, which can be associated with high costs5. Rationale: Major factors limiting the widespread use of allografts include infection, graft fracture, graft nonunion, and, in some locations, availability4,6. Our technique of allograft preparation with dual compression plating and triple-washing to provide mechanical and antimicrobial protection as well as augmented healing has shown reproducible results with low complication rates compared with the literature. Expected Outcomes: There have been high rates of long-term allograft survival (84.4%) following intercalary long-bone reconstruction at our institution, with lower complication rates than those presented in the literature. Important Tips: Transverse osteotomies of the allograft, made perpendicular to the long axis of the diaphysis/anatomical axis, are important to replicate the resected host bone. Transverse osteotomies, while inherently less stable than step-cut ones, allow for adjusting the rotation of the allograft segment as needed for maximal contact and compression, as well as restoration of anatomical limb rotation.It is important to perform meticulous clearance of the intramedullary contents while preserving the endosteal bone and allograft integrity. We would utilize hand-reaming rather than a power drill device, in order to prevent overreaming or breaking through the allograft bone.Place as few unicortical screws as possible into the allograft-cement construct in order to maintain its structural strength and minimize potential sites for vascular ingrowth and bone resorption. Acronyms & Abbreviations: K-wires = Kirschner wiresW/V = weight per volume.

Antibiotic Prophylaxis for Megaprosthetic Reconstructions: Drug and Dosing May Matter More than Duration.

In orthopedic oncology, the implant of a megaprosthetic device is standard of care after large-scale tumor resection involving segmental removal of bone. Infection remains the leading cause of implant failure, often resulting in major morbidity. Perioperative antibiotic practices for megaprosthetic reconstructions are not standardized and are based on guidelines for conventional joint arthroplasties. This study aims to evaluate the efficacy of current prophylactic strategies for megaprosthetic reconstructions. We conducted a retrospective review of megaprosthetic reconstructions performed at Duke University from 2001 to 2021. Logistic regression with GEE was used to assess whether a prolonged course of postoperative antibiotics is associated with infection risk. We assessed the microbial profile and corresponding susceptibilities of megaprosthetic infections through record review. Additionally, we designed a pharmacokinetic subgroup analysis using liquid chromatography-tandem mass spectrometry to quantify antibiotic concentrations in surgical tissue. Wilcoxon rank-sum tests were used to correlate tissue concentrations with infection risk. Out of 184 cases, 23 (12.5%) developed infection within 1 year. Extended postoperative antibiotics were not significantly associated with infection risk (P = 0.23). Among 18 culture-positive cases, 4 (22.2%) were caused by cefazolin-susceptible organisms. Median bone and muscle concentrations of cefazolin among cases that developed postoperative infection (0.065 ng/mL and 0.2 ng/mL, respectively) were significantly lower than those of cases that did not (0.42 ng/mL and 1.95 ng/mL, P < 0.01 and P = 0.03). This study is the first to comprehensively assess aspects of perioperative prophylaxis for megaprosthetic reconstructions. Extending postoperative antibiotics did not reduce infection risk. We detected a high frequency of cefazolin nonsusceptible organisms among postoperative infections. Additionally, intraoperative antibiotic tissue concentrations may be predictive of later infection. Future studies ought to examine optimal drug choices and dosing strategies.

How Do the Outcomes of Radiation-Associated Pelvic and Sacral Bone Sarcomas Compare to Primary Osteosarcomas following Surgical Resection?

Radiation-associated sarcoma of the pelvis and/or sacrum (RASB) is a rare but challenging disease process associated with a poor prognosis. We hypothesized that patients with RASB would have worse surgical and oncologic outcomes than patients diagnosed with primary pelvic or sacral bone sarcomas. This was a retrospective, multi-institution, comparative analysis. We reviewed surgically treated patients from multiple tertiary care centers who were diagnosed with a localized RASB. We also identified a comparison group including all patients diagnosed with a primary localized pelvic or sacral osteosarcoma/spindle cell sarcoma of bone (POPS). There were 35 patients with localized RASB and 73 patients with POPS treated with surgical resection. Patients with RASB were older than those with POPS (57 years vs. 38 years, p < 0.001). Patients with RASB were less likely to receive chemotherapy (71% for RASB vs. 90% for POPS, p = 0.01). Seventeen percent of patients with RASB died in the perioperative period (within 90 days of surgery) as compared to 4% with POPS (p = 0.03). Five-year disease-specific survival (DSS) (31% vs. 54% p = 0.02) was worse for patients with RASB vs. POPS. There was no difference in 5-year local recurrence free survival (LRFS) or metastasis free survival (MFS). RASB and POPS present challenging disease processes with poor oncologic outcomes. Rates of perioperative mortality and 5-year DSS are worse for RASB when compared to POPS.

Investigating readmission rates for patients undergoing oncologic resection and endoprosthetic reconstruction for primary sarcomas and tumors involving bone.

BACKGROUND: Little is known about the drivers of readmission in patients undergoing Orthopaedic oncologic resection. The goal of this study was to identify factors independently associated with 90-day readmission for patients undergoing oncologic resection and subsequent prosthetic reconstruction for primary tumors involving bone. METHODS: This was a retrospective comparative cohort study of patients treated from 2008 to 2019 who underwent endoprosthetic reconstruction for a primary bone tumor or soft tissue tumor involving bone, as well as those who underwent a revision endoprosthetic reconstruction if the primary endoprosthetic reconstruction was performed for an oncologic resection. The primary outcome measure was unplanned 90-day readmission. RESULTS: A total of 149 patients were identified who underwent 191 surgeries were for a primary bone or soft tissue tumor. The 90-day readmission rate was 28.3%. Female gender, depression, higher tumor grade, vascular reconstruction, longer procedure duration, longer length of stay (LOS), multiple surgeries during an admission and disposition to a Skilled Nursing Facility were associated with readmission (p < 0.05). In a multivariate analysis, female sex, higher tumor grade and longer procedure duration were independently associated with risk of readmission (p < 0.05). CONCLUSIONS: Readmission rates are high following endoprosthetic reconstruction for Orthopaedic oncologic resections. Further work is necessary to help minimize unplanned readmissions.

Intraoperative angiography imaging correlates with wound complications following soft tissue sarcoma resection.

For soft tissue sarcoma patients receiving preoperative radiation therapy, wound complications are common and potentially devastating. The purpose of this study was to assess the feasibility of intraoperative indocyanine green fluorescent angiography (ICGA) as a predictor of wound complications in these patients. A consecutive series of patients with soft tissue sarcoma of the extremities or pelvis who received neoadjuvant radiation and a subsequent radical resection received intraoperative ICGA with the SPY PHI device (Stryker Inc.) at the time of closure. Retrospective analysis of fluorescence signal along multiple points of the wound length was performed and quantified. The primary endpoint was wound complication, defined as delayed wound healing or wound dehiscence, within 3 months of surgery. Fourteen patients with preoperative irradiated soft tissue sarcoma were consecutively imaged. There were six patients with wound complications classified as "aseptic" in five cases. Using the ICGA, blinded surgeons correctly predicted wound complications in 75% of cases. During the inflow phase, a mean ratio of normal of 0.62 maximized the area under the curve (AUC = 0.90) for predicting wound complications with a sensitivity of 100% and specificity of 77.4%. During the peak phase, a mean ratio of normal of 0.55 maximized the AUC (0.95) for predicting wound complications with a sensitivity of 88.9% and a specificity of 100%. Intraoperative use of ICGA may help to predict wound complications in patients undergoing resection of preoperatively irradiated soft tissue sarcomas of the extremities and pelvis.

Is Advanced Imaging to Assess Rotator Cuff Integrity Before Shoulder Arthroplasty Cost-effective? A Decision Modeling Study.

BACKGROUND: Shoulder arthroplasty is increasingly performed for patients with symptoms of glenohumeral arthritis. Advanced imaging may be used to assess the integrity of the rotator cuff preoperatively because a deficient rotator cuff may be an indication for reverse shoulder arthroplasty (RSA) rather than anatomic total shoulder arthroplasty (TSA). However, the cost-effectiveness of advanced imaging in this setting has not been analyzed. QUESTIONS/PURPOSES: In this cost-effectiveness modeling study of TSA, all patients underwent history and physical examination, radiography, and CT, and we compared (1) no further advanced imaging, (2) selective MRI, (3) MRI for all, (4) selective ultrasound, and (5) ultrasound for all. METHODS: A simple chain decision model was constructed with a base-case 65-year-old patient with a 7% probability of a large-to-massive rotator cuff tear and a follow-up of 5 years. Strategies were compared using the incremental cost-effectiveness ratio (ICER) with a willingness to pay of both USD 50,000 and 100,000 per quality-adjusted life year (QALY) used, in accordance with the Second Panel on Cost-Effectiveness in Health and Medicine. Diagnostic test sensitivity and specificity were extracted from published systematic reviews and meta-analyses, and patient utilities were obtained using the Cost-Effectiveness Analysis Registry from the Center for the Evaluation of Value and Risk in Health. Final patient states were categorized as either inappropriate or appropriate based on the actual rotator cuff integrity and type of arthroplasty performed. Additionally, to evaluate the real-world impact of intraoperative determination of rotator cuff status, a secondary analysis was performed where all patients indicated for TSA underwent intraoperative rotator cuff examination to determine appropriate implant selection. RESULTS: Selective MRI (ICER of USD 40,964) and MRI for all (ICER of USD 79,182/QALY) were the most cost-effective advanced imaging strategies at a willingness to pay (WTP) of USD 50,000/QALY gained and 100,000/QALY gained, respectively. Overall, quality-adjusted life years gained by advanced soft tissue imaging were minimal: 0.04 quality-adjusted life years gained for MRI for all. Secondary analysis accounting for the ability of the surgeon to alter the treatment plan based on intraoperative rotator cuff evaluation resulted in the no further advanced imaging strategy as the dominant strategy as it was the least costly (USD 23,038 ± 2259) and achieved the greatest health utility (0.99 ± 0.05). The sensitivity analysis found the original model was the most sensitive to the probability of a rotator cuff tear in the population, with the value of advanced imaging increasing as the prevalence increased (rotator cuff tear prevalence greater than 12% makes MRI for all cost-effective at a WTP of USD 50,000/QALY). CONCLUSION: In the case of diagnostic ambiguity based on physical exam, radiographs, and CT alone, having both TSA and RSA available in the operating room appears more cost-effective than obtaining advanced soft tissue imaging preoperatively. However, performing selective MRI to assess rotator cuff integrity to indicate RSA or TSA is cost-effective if surgical preparedness, patient expectations, and implant availability preclude the ability to switch implants intraoperatively. LEVEL OF EVIDENCE: Level III, economic and decision analysis.

Extent of tumor fibrosis/hyalinization and infarction following neoadjuvant radiation therapy is associated with improved survival in patients with soft-tissue sarcoma.

INTRODUCTION: Current standard of care for most intermediate and high-grade soft-tissue sarcomas (STS) includes limb-preserving surgical resection with either neoadjuvant radiation therapy (NRT) or adjuvant radiation therapy. To date, there have been a few studies that attempt to correlate histopathologic response to NRT with oncologic outcomes in patients with STS. METHODS: Using our institutional database, we identified 58 patients who received NRT followed by surgical resection for primary intermediate or high-grade STS and 34 patients who received surgical resection without NRT but did receive adjuvant radiation therapy or did not receive any radiation therapy. We analyzed four histologic parameters of response to therapy: residual viable tumor, fibrosis/hyalinization, necrosis, and infarction (each ratiometrically determined). Data were stratified into two binary groups. Unadjusted, 5- and 10-year overall survival, and relapsed-free survival (RFS) were calculated using the Kaplan-Meier method. RESULTS: Analysis of pathologic characteristics showed that patients treated with NRT demonstrate significantly higher tumor infarction, higher tumor fibrosis/hyalinization, and a lower percent viable tumor compared with patients not treated with NRT (p < 0.0001). Based on Kaplan-Meier curve analysis and multivariate cox proportional hazard model for OS and RFS, patients treated with NRT and showing >12.5% tumor fibrosis/hyalinization have significantly higher overall survival and recurrence-free survival at 5 and 10 years. DISCUSSION AND CONCLUSION: We have identified three histopathologic characteristics-fibrosis, hyalinization, and infarction-that may serve as predictive biomarkers of response to NRT for STS patients. Future prospective studies will be needed to confirm this association.

Identifying Modifiable and Non-modifiable Risk Factors of Readmission and Short-Term Mortality in Chondrosarcoma: A National Cancer Database Study.

BACKGROUND: Limited data are available to inform the risk of readmission and short-term mortality in musculoskeletal oncology. The goal of this study was to identify factors independently associated with 30-day readmission and 90-day mortality following surgical resection of chondrosarcoma. METHODS: We retrospectively reviewed 6653 patients following surgical resection of primary chondrosarcoma in the National Cancer Database (2004-2017). Both demographic and clinicopathologic variables were assessed for correlation with readmission and short-term mortality utilizing univariate and multivariate logistic regression modeling. RESULTS: Of 220 readmissions (3.26%), risk factors independently associated with an increased risk of unplanned 30-day readmission included Charlson-Deyo Comorbidity Index (CDCC) (odds ratio [OR] 1.31; p = 0.027), increasing American Joint Committee on Cancer (AJCC) stage (OR 1.31; p = 0.004), undergoing major amputation (OR 2.38; p = 0.001), and axial skeletal location (OR 1.51; p = 0.028). A total of 137 patients died within 90 days of surgery (2.25%). Risk factors associated with increased mortality included the CDCC (OR 1.60; p = 0.001), increasing age (OR 1.06; p < 0.001), having Medicaid insurance status (OR 3.453; p = 0.005), living in a zip code with a higher educational attainment (OR 1.59; p = 0.003), increasing AJCC stage (OR 2.32; p < 0.001), longer postoperative length of stay (OR 1.015; p = 0.033), and positive surgical margins (OR 2.75; p = 0.001). Although a majority of the cohort did not receive radiation therapy (88.8%), receiving radiotherapy (OR 0.132; p = 0.010) was associated with a decreased risk of short-term mortality. CONCLUSIONS: Several tumor, treatment, and patient factors can help inform the risk of readmission and short-term mortality in patients with surgically treated chondrosarcoma.