[Analysis of 41 cases of non-metastatic Ewing's sarcoma in children]. / 儿童非转移性尤文肉瘤41例分析.

OBJECTIVES: To summarize the clinical characteristics, treatment outcomes, and prognostic factors of children with non-metastatic Ewing's sarcoma (ES). METHODS: A retrospective analysis was conducted on the clinical data of 41 children with non-metastatic ES diagnosed and treated at the Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine from January 2010 to December 2018. All patients underwent chemotherapy based on the RMS-2009 protocol of the center, and local treatment such as surgery and/or radiotherapy was performed according to risk grouping. The Kaplan-Meier method was used to calculate the overall survival (OS) and event-free survival (EFS) rates. Univariate prognostic analysis was performed using the log-rank test, and multivariate analysis was conducted with Cox regression. RESULTS: Of the 41 children, 21 were male and 20 were female. The median age at diagnosis was 7.7 years (range: 1.2-14.6 years). The median follow-up time for patients with event-free survival was 68.1 months (range: 8.1-151.7 months). As of the last follow-up, 33 patients were in complete remission, and the overall 5-year EFS and OS rates were (78±6)% and (82±6)%, respectively. Univariate analysis by the log-rank test showed that a tumor diameter ≥8 cm, time from diagnosis to start of local treatment ≥16 weeks, and incomplete surgical resection were associated with poor prognosis (P<0.05). Multivariate Cox regression analysis indicated that incomplete surgical resection (HR=8.381, 95%CI: 1.681-41.801, P=0.010) was an independent risk factor for poor prognosis in children with ES. Secondary tumors occurred in 2 cases. CONCLUSIONS: A comprehensive treatment strategy incorporating chemotherapy, surgery, and radiotherapy can improve the prognosis of children with ES. Poor prognosis is associated with an initial tumor diameter ≥8 cm, while complete surgical resection and early initiation of local treatment can improve outcomes.

Recurrence of solitary plasmacytoma in the liver 10 years after the onset of multiple bone lesions.

A 79-year-old man presented with a history of solitary plasmacytoma in the bone 10 years ago. Chemoradiotherapy was effective, and remission was maintained with intermittent treatment at relapse of the bone lesions. One year after the last treatment, a follow-up computed tomography (CT) scan revealed multiple liver masses, and a liver biopsy revealed plasmacytoma. There was no clonal plasma cell infiltration in the bone marrow, and the final diagnosis was solitary plasmacytomas of the liver. Although liver involvement is known in relapsed refractory multiple myeloma, solitary plasmacytoma in the relapsed stage confined to the liver is rare, and all previous reports have been from the initial presentation. To the best of our knowledge, this is the first recurrent case of solitary plasmacytoma of the liver.

Ewing's sarcoma in adolescents and adults - 10-year experience from a tertiary cancer center in India.

BACKGROUND: Ewing's sarcoma (EWS) is an aggressive small round cell tumor, affecting bone and soft tissues and is mostly seen in childhood and second decade of life. EWS accounts for 10-12% of bone tumors in more than 15 years age group and is even rarer after 40 years of age. MATERIALS AND METHODS: This retrospective analysis was conducted among patients aged more than 15 years with histologically proven EWS. RESULTS: Among 240 cases of EWS treated at our center during 2001-2010, 130 (54%) were more than 15 years of age. The median age was 20 years with a male: female ratio of 2.4:1. Ninety percent had skeletal EWS, 10% had extra skeletal EWS, and 37% patients were metastatic at presentation. Eighty-two received curative treatment with chemotherapy (vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide (VAC/IE)) along with local treatment, radiotherapy (RT) in 61, surgery alone in seven, and RT plus surgery in 14. Two- and 5-year overall survival (OS) was 43.3% and 25.5%, respectively, for the entire series. The OS for the non-metastatic group was 63.2% at 2 years and 36.5% at 5 years, and the progression free survival was 53.7% at 2 years and 37.8% at 5 years. High lactate dehydrogenase was found to be a significant poor prognostic factor (P = 0.001). Median OS for localized central EWS was 49.2 months and that for peripheral EWS was 24 months. Patients more than 20 years of age with non-metastatic disease had better OS compared to those with 15-20 years of age. CONCLUSION: Treatment of EWS requires a multidisciplinary approach with radical surgery and/or radiation to control local disease and multiagent chemotherapy to control systemic disease. Long-term follow-up is essential because of disease relapse and treatment-related complications.

Patterns and treatment outcomes of primary bone tumors in children treated at tertiary referral hospital, Ethiopia.

BACKGROUND: Bone tumors account for approximately 6% of all cancers in children. Malignant bone tumors, commonly occurring in children and adolescents, are associated with high mortality and morbidity. The overall survival of children with primary malignant bone tumors is affected by the stage of disease, time of diagnosis, and treatment response. Despite advanced treatment modalities with chemotherapy, surgery, and radiotherapy, bone tumor is the third leading cause of death in children with malignancy. Patients with metastatic disease at diagnosis have poor outcomes compared to localized disease at presentation. The 5-year Overall Survival and event-free survival in children with primary malignant bone tumors were 85.2% and 69.2%. The study aimed to assess the clinicopathological profile and treatment outcomes of children with primary malignant bone tumors in our setup. MATERIALS AND METHODS: A hospital-based cross-sectional study was conducted on 95 children who met the inclusion criteria through structured questionnaire. The collected data were analyzed using a statistical package for social sciences (SPSS) version 25. P-value < 0.05 was considered to be statistically significant. Kaplan Meier survival estimate was used for overall and event-free survival analysis. RESULTS: A total of ninety-five patients met the study inclusion criteria and the median age at diagnosis with primary malignant bone tumors was 10 years, with an interquartile range of 8-12 years. The duration of the illness from the onset of symptoms to the oncologic treatment center ranges from three weeks to 2 years with a mean duration of five months. Swelling was the commonest presenting symptom accounting for 95.8% (n = 91). Lower extremity was the commonest primary site of involvement accounting for 55.8% (n = 53) of children with primary malignant bone tumors. Osteosarcoma was the commonest malignant bone tumor constituted 66.3% (n = 63), followed by Ewing sarcoma at 33.7% (n = 32). About 41.2% (n = 39) of children had metastatic disease at presentation and the lung was the commonest site of distant metastasis. The Kaplan Meier survival estimate analysis showed the 1-year and 5-year overall survival probabilities for all pediatric primary malignant bone tumor patients were 65% (95% CI: 0.3-0.56) and 38% (95% CI:0.19-0.47) respectively. The 1-year and 5-year event-free survival probabilities were 55% (95% CI: 0.32-0.73) and 33% (95% CI: 0.10-0.59). The stage of the disease at presentation had a significant association with the outcome (p = 0.023). CONCLUSION: Our study showed the mean duration of the illness from the onset of symptoms to the oncologic treatment center was 5 months ranging from 3 weeks to 2 years. More than one-third of the presented with metastatic disease at presentation. The 1-year and 5-year overall survival (OS) probabilities of children with primary malignant bone tumors were low in our setup compared to other studies.

Visual analysis of bone malignancies immunotherapy: A bibliometric analysis from 2010 to 2023.

BACKGROUND: Bone malignancies (BM), including osteosarcoma, Ewing's sarcoma, chondrosarcoma, and chordoma, are characterized by high rates of recurrence and mortality, despite the availability of diverse treatment approaches. Immunotherapy has gained increasing importance in cancer treatment. However, there is a lack of comprehensive studies that utilize bibliometric analysis to explore immunotherapy for BM. METHODS: A literature search of English studies on BM and immunotherapy from 2010 to 2023 was conducted in the Web of Science Core Collection database. Bibliometric analysis tools such as VOSviewer, CiteSpace, and R Studio were utilized to examine global trends and research hotspots in this field. RESULTS: A total of 719 eligible articles, including 528 original research articles and 191 reviews, were analyzed. The number of publications has shown an increasing trend over the past 14 years, particularly in the last 5 years. The majority of the published articles on this topic originated from China (284 articles), followed by the United States and Japan. The institution with the highest number of publications and citations was the University of Texas MD Anderson Cancer Center (30 articles; 1638 citations). Dean A. Lee (12 articles) and Richard Gorlick (576 citations) were the authors with the highest contribution in terms of article count and citation count, respectively. Among these journals, Frontiers in Oncology had the highest number of articles (39 articles), while the Journal of Clinical Oncology had the highest number of citations (1878 citations). Additionally, there has been a shift in the keywords from "antitumor activity" and "NK cells" to popular topics such as "PD-L1," "open label," and "single arm." CONCLUSION: A better understanding of the current status and prospects of immunotherapy for BM is crucial for the rationale selection of appropriate BM patients for immunotherapy. This study is expected to help clinical physicians and researchers gain comprehensive insights into the developmental trends of BM immunotherapy, providing practical guidance for the application of immunotherapy in BM patients.

Clinical characteristics and prognoses in pediatric neuroblastoma with bone or liver metastasis: data from the SEER 2010-2019.

BACKGROUND: To investigate clinical characteristics, prognoses, and impacts of treatments on prognoses of neuroblastoma patients with bone or liver metastasis. METHODS: This retrospective cohort study extracted data from the Surveillance, Epidemiology, and End Results (SEER) database 2010-2019. The outcomes were 3-year cancer-specific survival (CSS) and 5-year CSS. Multivariable COX risk proportional models were established to assess the association between metastasis types and CSS. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. RESULTS: Totally 425 patients with metastatic neuroblastoma were eligible for 3-year CSS analysis and 320 for 5-year CSS analysis. For 3-year follow-up, 62 (14.59%) patients had liver metastasis alone, 289 (0.68%) had bone metastasis alone, and 74 (17.41%) had both liver and bone metastasis. For 5-year follow-up, 44 (13.75%) patients had liver metastasis alone, 223 (69.69%) had bone metastasis alone, and 53 (16.56%) had both liver and bone metastasis. Significant differences were observed in age, tumor size, surgery for the primary site, chemotherapy, radiation, brain metastasis, lung metastasis, and vital status between patients with liver metastasis alone, bone metastasis alone, and both liver and bone metastasis (all P < 0.05). Compared with patients with liver metastasis alone, patients with bone metastasis alone (HR = 2.30, 95%CI: 1.10-4.82, P = 0.028) or both (HR = 2.35, 95%CI: 1.06-5.20, P = 0.035) had significantly poorer 3-year CSS; patients with bone metastasis alone (HR = 2.32, 95%CI: 1.14-4.70, P = 0.020) or both liver and bone metastasis (HR = 2.33, 95%CI: 1.07-5.07, P = 0.032) exhibited significantly worse 5-year CSS than those with liver metastasis alone. In patients with bone metastasis, those with chemotherapy had significantly better 3-year CSS than those without (HR = 0.24, 95%CI: 0.07-0.75, P = 0.014). Among patients with liver metastasis, receiving radiation was associated with significantly worse 3-year CSS (HR = 2.00, 95%CI: 1.05-3.81, P = 0.035). CONCLUSION: Compared with patients with liver metastasis alone, those with bone metastasis alone or both had poorer 3- and 5-year CSS. For patients with bone metastasis, undergoing chemotherapy was associated with better 3-year CSS. For patients with liver metastasis, receiving radiation was associated with worse 3-year CSS.

Chimeric antigen receptor T cells in the treatment of osteosarcoma (Review).

Osteosarcoma (OS) is a frequently occurring primary bone tumor, mostly affecting children, adolescents and young adults. Before 1970, surgical resection was the main treatment method for OS, but the clinical results were not promising. Subsequently, the advent of chemotherapy has improved the prognosis of patients with OS. However, there is still a high incidence of metastasis or recurrence, and chemotherapy has several side effects, thus making the 5­year survival rate markedly low. Recently, chimeric antigen receptor T (CAR­T) cell therapy represents an alternative immunotherapy approach with significant potential for hematologic malignancies. Nevertheless, the application of CAR­T cells in the treatment of OS faces numerous challenges. The present review focused on the advances in the development of CAR­T cells to improve their clinical efficacy, and discussed ways to overcome the difficulties faced by CAR T­cell therapy for OS.

The Development and Characterization of a Next-Generation Oncolytic Virus Armed with an Anti-PD-1 sdAb for Osteosarcoma Treatment In Vitro.

Osteosarcoma (OS) is a primary bone malignancy characterized by an aggressive nature, limited treatment options, low survival rate, and poor patient prognosis. Conditionally replicative adenoviruses (CRAds) armed with immune checkpoint inhibitors hold great potential for enhanced therapeutic efficacy. The present study aims to investigate the anti-tumor efficacy of CAV2-AU-M2, a CAV2-based CRAd armed with an anti-PD-1 single-domain antibody (sdAb), against OS cell lines in vitro. The infection, conditional replication, cytopathic effects, and cytotoxicity of CAV2-AU-M2 were tested in four different OS cell lines in two-dimensional (2D) and three-dimensional (3D) cell cultures. CAV2-AU-M2 showed selective replication in the OS cells and induced efficient tumor cell lysis and death. Moreover, CAV2-AU-M2 produced an anti-PD-1 sdAb that demonstrated effective binding to the PD-1 receptors. This study demonstrated the first CRAd armed with an anti-PD-1 sdAb. This combined approach of two distinct immunotherapies is intended to enhance the anti-tumor immune response in the tumor microenvironment.

Bone mimetic environments support engineering, propagation, and analysis of therapeutic response of patient-derived cells, ex vivo and in vivo.

Bone metastases are the most common milestone in the lethal progression of prostate cancer and prominent in a substantial portion of renal malignancies. Interactions between cancer and bone host cells have emerged as drivers of both disease progression and therapeutic resistance. To best understand these central host-epithelial cell interactions, biologically relevant preclinical models are required. To achieve this goal, we here established and characterized tissue-engineered bone mimetic environments (BME) capable of supporting the growth of patient-derived xenograft (PDX) cells, ex vivo and in vivo. The BME consisted of a polycaprolactone (PCL) scaffold colonized by human mesenchymal stem cells (hMSCs) differentiated into osteoblasts. PDX-derived cells were isolated from bone metastatic prostate or renal tumors, engineered to express GFP or luciferase and seeded onto the BMEs. BMEs supported the growth and therapy response of PDX-derived cells, ex vivo. Additionally, BMEs survived after in vivo implantation and further sustained the growth of PDX-derived cells, their serial transplant, and their application to study the response to treatment. Taken together, this demonstrates the utility of BMEs in combination with patient-derived cells, both ex vivo and in vivo. STATEMENT OF SIGNIFICANCE: Our tissue-engineered BME supported the growth of patient-derived cells and proved useful to monitor the therapy response, both ex vivo and in vivo. This approach has the potential to enable co-clinical strategies to monitor bone metastatic tumor progression and therapy response, including identification and prioritization of new targets for patient treatment.

Bone metastatic cancer of unknown primary at initial presentation

Introduction Cancer of unknown primary (CUP) is a challenging malignancy. The purpose of this study was to investigate the clinical characteristics and prognosis of bone metastatic CUP using the population-based Surveillance, Epidemiology, and End Results (SEER) database. Methods From the SEER database, we identified 1908 patients with bone metastatic CUP at initial presentation between 2010 and 2018. Histology was subdivided following International Classification of Diseases for Oncology codes as Adenocarcinoma, Squamous cell, Neuroendocrine, or Carcinoma not otherwise specified (NOS). Cox proportional hazard modeling was applied using factors of age, sex, ethnicity, histological subtype, and therapeutic intervention. Results Among the 1908 patients, histology was Neuroendocrine in 240 patients, Squamous cell in 201 patients, Adenocarcinoma in 810 patients and NOS in 657 patients. In each subtype, patients tended to be predominantly male and white. Chemotherapy was introduced for 28% of patients and radiation for 34% in the entire cohort. Survival in patients with bone metastatic CUP was unfavorable, with a median survival of 2 months. Among the histological subtypes, Adenocarcinoma showed shorter survival than the other groups. In addition, treatment interventions such as chemotherapy and radiation therapy prolonged survival, particularly for Squamous cell, Adenocarcinoma and NOS, but not for Neuroendocrine. Discussion Bone metastatic CUP showed extremely poor prognosis, but treatment interventions such as chemotherapy and radiation generally offered survival benefits. Further randomized clinical research is needed to confirm the present results (AU)

Microvessel Density (MVD) in Patients with Osteosarcoma: A Systematic Review and Meta-Analysis.

A meta-analysis was designed and conducted to estimate the effect of tumoral microvessel density (MVD) on the survival of patients with osteosarcoma. There was no difference between high and low MVD regarding the overall (OS) and disease-free (DFS) survival. Low MVD tumors displayed a lower DFS at the third year of follow-up. Although primary metastases did not affect the mean MVD measurements, tumors with a good chemotherapy response had a higher MVD value. Although no significant differences between tumoral MVD, OS and DFS were found, good adjuvant therapy responders had a significant higher vascularization pattern.

Primary vascular tumors of bone: A comprehensive literature review on classification, diagnosis and treatment.

Primary vascular tumors of bone are a heterogeneous group of neoplasms, ranging from benign hemangiomas to frankly malignant epithelioid hemangioendotheliomas and angiosarcomas. Over the years, their classification has been a matter of discussion, due to morphologic similarities and uncertainty regarding biologic behavior. Over the past decade, with the development of next-generation sequencing, there has been a significant improvement in the molecular characterization of these lesions. The integration of their morphologic, immunohistochemical and molecular features has led to a better stratification, with important prognostic and therapeutic implications. Nevertheless, primary vascular bone tumors still represent a challenge for medical oncologists. Given their rarity and heterogeneity, in the last few years, there has been no significant progress in medical treatment options, so further research is needed. Here we present a review of the current knowledge regarding primary vascular tumors of the bone, correlating clinicopathologic features with tumor behavior and therapeutic approaches.

[Research progress in clinical diagnosis and treatment of osteosarcoma of the jaw].

Osteosarcoma of the jaw (JOS), is a relatively rare type of osteosarcoma, with a unique pathogenesis and pathological manifestations. The clinical manifestation of JOS is not characteristic, and it often needs to be diagnosed by combining radiological and pathological examination. At present, the conventional treatment of JOS is a comprehensive treatment based on surgery and supplemented by radiotherapy and chemotherapy. Recently, the emergence of new therapies such as immunotherapy, gene therapy, phototherapy and traditional Chinese medicine has provided more choices for treatment and brought new hope to patients with JOS. Therefore, this article summarized the current understanding of diagnosis and the latest treatment development of JOS.

Cell membrane-anchored and tumor-targeted IL-12 T-cell therapy destroys cancer-associated fibroblasts and disrupts extracellular matrix in heterogenous osteosarcoma xenograft models.

BACKGROUND: The extracellular matrix (ECM) and cancer-associated fibroblasts (CAFs) play major roles in tumor progression, metastasis, and the poor response of many solid tumors to immunotherapy. CAF-targeted chimeric antigen receptor-T cell therapy cannot infiltrate ECM-rich tumors such as osteosarcoma. METHOD: In this study, we used RNA sequencing to assess whether the recently invented membrane-anchored and tumor-targeted IL-12-armed (attIL12) T cells, which bind cell-surface vimentin (CSV) on tumor cells, could destroy CAFs to disrupt the ECM. We established an in vitro model of the interaction between osteosarcoma CAFs and attIL12-T cells to uncover the underlying mechanism by which attIL12-T cells penetrate stroma-enriched osteosarcoma tumors. RESULTS: RNA sequencing demonstrated that attIL12-T cell treatment altered ECM-related gene expression. Immunohistochemistry staining revealed disruption or elimination of high-density CAFs and ECM in osteosarcoma xenograft tumors following attIL12-T cell treatment, and CAF/ECM density was inversely correlated with T-cell infiltration. Other IL12-armed T cells, such as wild-type IL-12-targeted or tumor-targeted IL-12-T cells, did not disrupt the ECM because this effect depended on the engagement between CSV on the tumor cell and its ligand on the attIL12-T cells. Mechanistic studies found that attIL12-T cell treatment elevated IFNγ production on interacting with CSV+ tumor cells, suppressing transforming growth factor beta secretion and in turn upregulating FAS-mediated CAF apoptosis. CAF destruction reshaped the tumor stroma to favor T-cell infiltration and tumor inhibition. CONCLUSIONS: This study unveiled a novel therapy-attIL12-T cells-for targeting CAFs/ECM. These findings are highly relevant to humans because CAFs are abundant in human osteosarcoma.

Racial disparities in the management and outcomes of primary osseous neoplasms of the spine: a SEER analysis.

PURPOSE: Primary osseous neoplasms of the spine, including Ewing's sarcoma, osteosarcoma, chondrosarcoma, and chordoma, are rare tumors with significant morbidity and mortality. The present study aims to identify the prevalence and impact of racial disparities on management and outcomes of patients with these malignancies. METHODS: The 2000 to 2020 Surveillance, Epidemiology, and End Results (SEER) Registry, a cancer registry, was retrospectively reviewed to identify patients with Ewing's sarcoma, osteosarcoma, chondrosarcoma, or chordoma of the vertebral column or sacrum/pelvis. Study patients were divided into race-based cohorts: White, Black, Hispanic, and Other. Demographics, tumor characteristics, treatment variables, and mortality were assessed. RESULTS: 2,415 patients were identified, of which 69.8% were White, 5.8% Black, 16.1% Hispanic, and 8.4% classified as "Other". Tumor type varied significantly between cohorts, with osteosarcoma affecting a greater proportion of Black patients compared to the others (p < 0.001). A lower proportion of Black and Other race patients received surgery compared to White and Hispanic patients (p < 0.001). Utilization of chemotherapy was highest in the Hispanic cohort (p < 0.001), though use of radiotherapy was similar across cohorts (p = 0.123). Five-year survival (p < 0.001) and median survival were greatest in White patients (p < 0.001). Compared to non-Hispanic Whites, Hispanic (p < 0.001) and "Other" patients (p < 0.001) were associated with reduced survival. CONCLUSION: Race may be associated with tumor characteristics at diagnosis (including subtype, size, and site), treatment utilization, and mortality, with non-White patients having lower survival compared to White patients. Further studies are necessary to identify underlying causes of these disparities and solutions for eliminating them.

Surface and Global Proteome Analyses Identify ENPP1 and Other Surface Proteins as Actionable Immunotherapeutic Targets in Ewing Sarcoma.

PURPOSE: Ewing sarcoma is the second most common bone sarcoma in children, with 1 case per 1.5 million in the United States. Although the survival rate of patients diagnosed with localized disease is approximately 70%, this decreases to approximately 30% for patients with metastatic disease and only approximately 10% for treatment-refractory disease, which have not changed for decades. Therefore, new therapeutic strategies are urgently needed for metastatic and refractory Ewing sarcoma. EXPERIMENTAL DESIGN: This study analyzed 19 unique Ewing sarcoma patient- or cell line-derived xenografts (from 14 primary and 5 metastatic specimens) using proteomics to identify surface proteins for potential immunotherapeutic targeting. Plasma membranes were enriched using density gradient ultracentrifugation and compared with a reference standard of 12 immortalized non-Ewing sarcoma cell lines prepared in a similar manner. In parallel, global proteome analysis was carried out on each model to complement the surfaceome data. All models were analyzed by Tandem Mass Tags-based mass spectrometry to quantify identified proteins. RESULTS: The surfaceome and global proteome analyses identified 1,131 and 1,030 annotated surface proteins, respectively. Among surface proteins identified, both approaches identified known Ewing sarcoma-associated proteins, including IL1RAP, CD99, STEAP1, and ADGRG2, and many new cell surface targets, including ENPP1 and CDH11. Robust staining of ENPP1 was demonstrated in Ewing sarcoma tumors compared with other childhood sarcomas and normal tissues. CONCLUSIONS: Our comprehensive proteomic characterization of the Ewing sarcoma surfaceome provides a rich resource of surface-expressed proteins in Ewing sarcoma. This dataset provides the preclinical justification for exploration of targets such as ENPP1 for potential immunotherapeutic application in Ewing sarcoma. See related commentary by Bailey, p. 934.

Manual and Semi-Automated Measurement and Calculation of Osteosarcoma Treatment Effect Using Whole Slide Image and Qupath.

INTRODUCTION: In osteosarcoma, the most significant indicator of prognosis is the histologic changes related to tumor response to preoperative chemotherapy, such as necrosis. We have developed a method to measure the osteosarcoma treatment effect using whole slide image (WSI) with an open-source digital image analytical software Qupath. MATERIALS AND METHODS: In Qupath, each osteosarcoma case was treated as a project. All H&E slides from the entire representative slice of osteosarcoma were scanned into WSIs and imported into a project in Qupath. The regions of tumor and tumor necrosis were annotated, and their areas were measured in Qupath. In order to measure the osteosarcoma treatment effect, we needed to calculate the percentage of total necrosis area over total tumor area. We developed a tool that can automatically extract all values of tumor and necrosis areas from a Qupath project into an Excel file, sum these values for necrosis and whole tumor respectively, and calculate necrosis/tumor percentage. CONCLUSION: Our method that combines WSI with Qupath can provide an objective measurement to facilitate pathologist's assessment of osteosarcoma response to treatment. The proposed approach can also be used for other types of tumors that have clinical need for post-treatment response assessment.

Dual-Targeting Biomimetic Semiconducting Polymer Nanocomposites for Amplified Theranostics of Bone Metastasis.

Bone metastasis is a type of metastatic tumors that involves the spreads of malignant tumor cells into skeleton, and its diagnosis and treatment remain a big challenge due to the unique tumor microenvironment. We herein develop osteoclast and tumor cell dual-targeting biomimetic semiconducting polymer nanocomposites (SPFeNOC ) for amplified theranostics of bone metastasis. SPFeNOC contain semiconducting polymer and iron oxide (Fe3 O4 ) nanoparticles inside core and surface camouflaged hybrid membrane of cancer cells and osteoclasts. The hybrid membrane camouflage enables their targeting to both metastatic tumor cells and osteoclasts in bone metastasis through homologous targeting mechanism, thus achieving an enhanced nanoparticle accumulation in tumors. The semiconducting polymer mediates near-infrared (NIR) fluorescence imaging and sonodynamic therapy (SDT), and Fe3 O4 nanoparticles are used for magnetic resonance (MR) imaging and chemodynamic therapy (CDT). Because both cancer cells and osteoclasts are killed synchronously via the combinational action of SDT and CDT, the vicious cycle in bone metastasis is broken to realize high antitumor efficacy. Therefore, 4T1 breast cancer-based bone metastasis can be effectively detected and cured by using SPFeNOC as dual-targeting theranostic nanoagents. This study provides an unusual biomimetic nanoplatform that simultaneously targets osteoclasts and cancer cells for amplified theranostics of bone metastasis.