Primary Tumor Research Articles

Metastatic cancer in a medieval skeleton from the Principality of Liechtenstein.

We present a presumptive case of metastatic carcinoma in an individual from the 11th/12th century CE from Vaduz, Principality of Liechtenstein. The skeleton exhibits extensive new bone formation in the axial skeleton and the proximal humerus and femur. Radiological examinations revealed further sclerotic lesions in the clavicles, the manubrium, the sternum, the femoral diaphysis, and possibly the frontal. The pelvic bones and the sacrum, as well as the spine, are the most heavily affected skeletal regions. The newly formed bone in some lesions has a "sun-burst" appearance. The sex and age at death of the individual, the distribution and the osteoblastic nature of the lesions suggest that prostate carcinoma is the most likely primary tumor.

Cell-specific cross-talk proteomics reveals cathepsin B signaling as a driver of glioblastoma malignancy near the subventricular zone.

Glioblastoma (GBM) is the most prevalent and aggressive malignant primary brain tumor. GBM proximal to the lateral ventricles (LVs) is more aggressive, potentially because of subventricular zone contact. Despite this, cross-talk between GBM and neural stem/progenitor cells (NSC/NPCs) is not well understood. Using cell-specific proteomics, we show that LV-proximal GBM prevents neuronal maturation of NSCs through induction of senescence. In addition, GBM brain tumor-initiating cells (BTICs) increase expression of cathepsin B (CTSB) upon interaction with NPCs. Lentiviral knockdown and recombinant protein experiments reveal that both cell-intrinsic and soluble CTSB promote malignancy-associated phenotypes in BTICs. Soluble CTSB stalls neuronal maturation in NPCs while promoting senescence, providing a link between LV-tumor proximity and neurogenesis disruption. Last, we show LV-proximal CTSB up-regulation in patients, showing the relevance of this cross-talk in human GBM biology. These results demonstrate the value of proteomic analysis in tumor microenvironment research and provide direction for new therapeutic strategies in GBM.

Role of textural and radiomic analysis parameters in predicting histopathological parameters of the tumor in breast cancer patients.

Texture and radiomic analysis characterizes the tumor's phenotype and evaluates its microenvironment in quantitative terms. This study aims to investigate the role of textural and radiomic analysis parameters in predicting histopathological factors in breast cancer patients. Two hundred and twelve primary breast cancer patients underwent 18F-FDG PET/computed tomography for staging. The images were processed in a commercially available textural analysis software. ROI was drawn over the primary tumor with a 40% threshold and was processed further to derive textural and radiomic parameters. These parameters were then compared with histopathological factors of tumor. Receiver-operating characteristic analysis was performed with a P-value <0.05 for statistical significance. The significant parameters were subsequently utilized in various machine learning models to assess their predictive accuracy. A retrospective study of 212 primary breast cancer patients was done. Among all the significant parameters, SUVmin, SUVmean, SUVstd, SUVmax, discretized HISTO_Entropy, and gray level co-occurrence matrix_Contrast were found to be significantly associated with ductal carcinoma type. Four parameters (SUVmin, SUVmean, SUVstd, and SUVmax) were significant in differentiating the luminal subtypes of the tumor. Five parameters (SUVmin, SUVmean, SUVstd, SUVmax, and SUV kurtosis) were significant in predicting the grade of the tumor. These parameters showcased robust capabilities in predicting multiple histopathological parameters when tested using machine learning algorithms. Though textural analysis could not predict hormonal receptor status, lymphovascular invasion status, perineural invasion status, microcalcification status of tumor, and all the molecular subtypes of the tumor, it could predict the tumor's histologic type, triple-negative subtype, and score of the tumor noninvasively.

Disrupting YAP1-mediated glutamine metabolism induces synthetic lethality alongside ODC1 inhibition in osteosarcoma.

Osteosarcoma, a highly malignant primary bone tumor primarily affecting adolescents, frequently develops resistance to initial chemotherapy, leading to metastasis and limited treatment options. Our study aims to uncover novel therapeutic targets for metastatic and recurrent osteosarcoma. In this study, we proved the potential of modulating the YAP1-regulated glutamine metabolic pathway to augment the response of OS to DFMO. We initially employed single-cell transcriptomic data to gauge the activation level of polyamine metabolism in MTAP-deleted OS patients. This was further substantiated by transcriptome sequencing data from recurrent and non-recurrent patient tissues, confirming the activation of polyamine metabolism in progressive OS. Through high-throughput drug screening, we pinpointed CIL56, a YAP1 inhibitor, as a promising candidate for a combined therapeutic strategy with DFMO. In vivo, we utilized PDX and CDX models to validate the therapeutic efficacy of this drug combination. In vitro, we conducted western blot analysis, qPCR analysis, immunofluorescence staining, and PuMA experiments to monitor alterations in molecular expression, distribution, and tumor metastasis capability. We employed CCK-8 and colony formation assays to assess the proliferative capacity of cells in the experimental group. We used flow cytometry and reactive oxygen probes to observe changes in ROS and glutamine metabolism within the cells. Finally, we applied RNA-seq in tandem with metabolomics to identify metabolic alterations in OS cells treated with a DFMO and CIL56 combination. This enabled us to intervene and validate the role of the YAP1-mediated glutamine metabolic pathway in DFMO resistance. Through single-cell RNA-seq data analysis, we pinpointed a subset of late-stage OS cells with significantly upregulated polyamine metabolism. This upregulation was further substantiated by transcriptomic profiling of recurrent and non-recurrent OS tissues. High-throughput drug screening revealed a promising combination strategy involving DFMO and CIL56. DFMO treatment curbs the phosphorylation of YAP1 protein in OS cells, promoting nuclear entry and initiating the YAP1-mediated glutamine metabolic pathway. This reduces intracellular ROS levels, countering DFMO's anticancer effect. The therapeutic efficacy of DFMO can be amplified both in vivo and in vitro by combining it with the YAP1 inhibitor CIL56 or the glutaminase inhibitor CB-839. This underscores the significant potential of targeting the YAP1-mediated glutamine metabolic pathway to enhance efficacy of DFMO. Our findings elucidate YAP1-mediated glutamine metabolism as a crucial bypass mechanism against DFMO, following the inhibition of polyamine metabolism. Our study provides valuable insights into the potential role of DFMO in an "One-two Punch" therapy of metastatic and recurrent osteosarcoma.

Primary malignant perivascular epithelioid cell tumors with TFE3 rearrangement of bone: a clinicopathological analysis of two cases

Primary malignant perivascular epithelioid cell tumors with TFE3 rearrangement of bone: a clinicopathological analysis of two cases

The Peptidoglycan Recognition Protein 1 confers immune evasive properties on pancreatic cancer stem cells

ObjectivePancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options, particularly with immune checkpoint inhibitors. Highly chemoresistant ‘stem-like’ cells, known as cancer stem cells (CSCs), are implicated in PDAC aggressiveness. Thus, comprehending...

Outcome of intraoperative brachytherapy as asalvage treatment for locally recurrent rectal cancer.

Locally advanced recurrent rectal cancer (RRC) requires amultimodal approach. Intraoperative high-dose-rate brachytherapy (HDR-BT) may reduce the risk of local recurrence. However, the optimal therapeutic regimen remains unclear. The aim of this retrospective monocentric study was to evaluate the toxicity of HDR-BT after resection of RRC. Between 2018 and 2022, 17patients with RRC received resection and HDR-BT. HDR-BT was delivered alone or as an anticipated boost with amedian dose of 13 Gy (range 10-13 Gy) using an 192iridium microSelectron HDR remote afterloader (Elekta AB, Stockholm, Sweden). All participants were followed for assessment of acute and late adverse events using the Common Terminology Criteria for Adverse Events version5.0 and the modified Late Effects in Normal Tissues criteria (subjective, objective, management, and analytic; LENT-SOMA) at 3‑ to 6‑month intervals. Atotal of 17patients were treated by HDR-BT with median dose of 13 Gy (range 10-13 Gy). Most patients (47%) had an RRC tumor stage of cT3‑4 N0. At the time of RRC diagnosis, 7patients (41.2%) had visceral metastases (hepatic, pulmonary, or peritoneal) in the sense of oligometastatic disease. The median interval between primary tumor resection and diagnosis of RRC was 17months (range 1-65months). In addition to HDR-BT, 2patients received long-course chemoradiotherapy (CRT; up to 50.4 Gy in 1.8-Gy fractions) and 2patients received short-course CRT up to 36 Gy in 2‑Gy fractions. For concomitant CRT, all patients received 5‑fluorouracil (5-FU) or capecitabine. Median follow-up was 13months (range 1-54). The most common acute grade1-2 toxicities were pain in 7patients (41.2%), wound healing disorder in 3patients (17.6%), and lymphedema in 2patients (11.8%). Chronic toxicities were similar: grade1-2 pain in 7patients (41.2%), wound healing disorder in 3patients (17.6%), and incontinence in 2patients (11.8%). No patient experienced agrade ≥3 event. Reirradiation using HDR-BT is well tolerated with low toxicity. An individualized multimodality approach using HDR-BT in the oligometastatic setting should be evaluated in prospective multi-institutional studies.

Application of cell blocks to assist in precise cytological diagnosis of serous effusion

Objective: To investigate the importance of cell block and immunohistochemistry in the accurate diagnosis of serous effusion. Methods: A retrospective study was conducted on 3 124 cases of serous effusion from the Department of Pathology, Beijing Hospital from 2018 to 2022, include 2 213 cases of pleural effusion, 768 cases of peritoneal effusion, 143 cases of pericardial effusion. There were 1 699 males (54.4%) and 1 425 females (45.6%), average age 69 years old. Of which 1 292 cases were prepared with cell blocks and examined with immunohistochemical stain. Results: The percentage of malignant diagnosis increased from 64.9% (839/1 292) to 84.0% (1 086/1 292) after cell block preparation, and 1 086 cases were accurately diagnosed with histological type and/or origin of primary tumor. The undetermined diagnosis of suspected malignancy decreased from 13.3% (172/1 292) to 0.1% (1/1 292) and that of atypical hyperplasia from 18.8% (243/1 292) to 0.4% (5/1 292). The negative result for malignancy rate increased from 3.0% (38/1 292) to 15.5% (200/1 292). The differences highlighted above were statistically significant (Pearson's chi-squared test=12.739, P<0.01). Conclusion: Application of immunohistochemistry based on cell block can significantly improve malignant diagnosis in serous effusion, identify tumor origin and histological type as well as decrease the uncertain diagnosis.

Surgical treatment and outcome of primary rib tumours in cats: eight cases (2016-2023).

To describe the clinical features and oncologic outcome for cats with primary rib tumours. Medical records for cats with surgically treated primary rib tumours from six veterinary referral centres were reviewed. Signalment, preoperative clinical signs, reconstruction technique, and surgical and oncologic outcome were retrieved from medical records or by telephone interview with owners and/or referring veterinarians. Of the eight cats with primary rib tumours, three had hemangiosarcoma, two had osteosarcoma and one cat each had chondrosarcoma, osteochondroma and osteoma. The size of the primary rib mass ranged from 2 × 2 × 1.6 cm to 9 × 7 × 7.5 cm. Three minor and one major complication developed during the immediate post-operative period. Surgery consisted of thoracic wall resection in all cats. All animals survived the procedure and the median time to discharge was 3 days. The survival time for benign tumours was 150 (case 5) and 466 (case 4) days, while for malignant tumours ranged from 105 to 550 days (cases 1 to 3, cases 6 to 8). Hemangiosarcoma and osteosarcoma were the most represented primary rib tumours in this cohort of cats. Wide surgical excision and adjuvant chemotherapy is recommended for cats with hemangiosarcoma and osteosarcoma, but the prognosis remains guarded. Prognosis appears to be fair for the other tumour types.

Comparative analysis of dual immune checkpoint inhibitor combination therapy versus immune checkpoint inhibitor plus tyrosine kinase inhibitor combination therapy for renal cell carcinoma with inferior vena cava tumor thrombosis.

Whether immune checkpoint inhibitor (ICI) plus ICI combination therapy or ICI plus tyrosine kinase inhibitor (TKI) combination therapy is useful for renal cell carcinoma (RCC) with inferior vena cava tumor thrombosis (IVCTT) remains unclear. We retrospectively evaluated the therapeutic effects and incidence of treatment-related adverse events (TRAEs) associated with ICI-based combination therapy in 36 patients with advanced RCC with IVCTT. The median age at initiation of treatment was 71years; the IVCTT stages were cT3b in 22 patients and cT3c in 14. The ICI-ICI and ICI-TKI groups comprised 15 and 21 patients, respectively. Median tumor shrinkage at the best response showed that the primary tumor diameter decreased by 1.8cm (22%), and the IVCTT height decreased by 1.5cm (26%). A higher proportion of patients in the ICI-TKI group experienced tumor shrinkage than those in the ICI-ICI group (primary tumor, p = 0.0325; IVCTT, p = 0.0112). Approximately 27% of patients experienced an increase in the IVCTT height with ICI-ICI combination therapy. No significant difference was observed in the relative tumor shrinkage of IVCTT, primary or level-down staging of IVCTT, other treatment effects, incidence of TRAEs, surgical outcomes, or prognosis between the groups. ICI-based combination therapy is effective against IVCTT and primary RCC. Although ICI-ICI is associated with a higher probability of tumor growth compared with ICI-TKI in the frequency of tumor regression, both therapies may be almost equally effective against primary RCC with IVCTT.

Post-operative outcomes of primary benign orbital tumor resection are independent of tumor size and morphology.

Using 3D modeling, we studied the influence of orbital tumor morphology on post-operative outcomes. Orbital tumor volume did not influence postoperative complication rates. Less spherical tumors may be correlated with a more extensive surgical approach.

Glutamine withdrawal leads to the preferential activation of lipid metabolism in metastatic colorectal cancer

IntroductionGlutamine is a non-essential amino acid that is critical for cell growth. However, the differential metabolism of l-glutamine in metastatic versus primary colorectal cancer (CRC) has not been evaluated adequately. Materials and methodsDifferential expression of glutamine-related genes was determined in primary versus metastatic CRC. Univariate Cox regression and hierarchical clustering were used to generate a gene signature for prognostication. Untargeted metabolomics and 18O based fluxomics were used to identify differential metabolite levels and energy turnover in the paired primary (SW480) and metastatic (SW620) CRC cells. Western blot and qRT-PCR were used to validate differential gene expression. Subcellular localization of E-cadherin was determined by immunocytochemistry. Lipid droplets were visualized with Nile Red. ResultsThe GO term “Glutamine metabolism” was significantly enriched in metastatic versus primary tumors. Supporting this, SW620 cells showed decreased membrane localization of E-cadherin and increased motility upon l-Glutamine withdrawal. A glutamine related signature associated with worse prognosis was identified and validated in multiple datasets. A fluxomics assay revealed a slower TCA cycle in SW480 and SW620 cells upon l-Glutamine withdrawal. SW620 cells, however, could maintain high ATP levels. Untargeted metabolomics indicated the preferential metabolism of fatty acids in SW620 but not SW480 cells. Lipids were mainly obtained from the environment rather than by de novo synthesis. ConclusionsMetastatic CRC cells can display aberrant glutamine metabolism. We show for the first time that upon l-glutamine withdrawal, SW620 (but not SW480) cells were metabolically plastic and could metabolize lipids for survival and cellular motility.

Outcome of whole brain irradiation with a dose-escalated simultaneous-integrated boost in patients with multiple large and/or diffuse brain metastases: real live data and review of the literature

BackgroundWe retrospectively investigate feasibility and safety of whole brain radiotherapy (WBRT) including a simultaneous-integrated boost technique (WBRT-SIB) in a cohort of patients with a very poor prognosis suffering from multiple and/or large brain metastases, unfavorable primary histology, poor performance status and/or symptomatic BMs.Materials and MethodsThirty-five patients with high brain tumor burden, extracranial metastases and low life-expectancy were treated with WBRT-SIB mostly with 35-42 Gy/14 fractions. All metastases were boosted in patients with up to 12 BMs. In patients with > 12 BM, large and/or small metastases in critical brain regions were boosted up to a maximum of 12 SIB volumes.ResultsThe median number of BM was 8 (range 2–45) and the median BM diameter was 12 mm (range 4–90 mm). Fifteen (43%) patients had ≥ 10 BMs and 25 patients presented with a Karnofski index ≤ 80%. Primary tumor histology was NSCLC (n = 13), SCLC (n = 11), breast cancer (n = 7), melanoma (n = 2), other (n = 2). The median iPFS was not reached, and 12- and 18-months iPFS were 75% and 50%, respectively. Overall, seven patients had intracranial progression: two patients within the SIB and WBRT area, one patient only within the SIB region and four patients had new BMs in the WBRT volume alone. The median iPFS for non-SCLC patients was 17 months and the 12- and 18-month iPFS were 56.8% and 28.4%, respectively. There was no significant OS difference between SCLC-group and non-SCLC patients (p = 0.38). Overall, median OS was 8.7 months and 1-year OS was 25%. The treatment was generally well-tolerated with no observed cases of radionecrosis.ConclusionOur WBRT-SIB approach involves a combination of whole brain radiotherapy and a simultaneous integrated boost to specific tumor volumes, and its effectiveness is compared with other treatment modalities in the literature. Further research, including prospective studies with larger patient cohorts, is necessary to validate and refine the findings.

Prevalence of Helicobacter pylori infection among patients with esophageal carcinoma

BACKGROUND Helicobacter pylori (H. pylori ) is a widespread microorganism related to gastric adenocarcinoma (AC). In contrast, it has been reported that an inverse association exists between H. pylori infection and esophageal carcinoma. The mechanisms underlying this supposedly protective effect remain controversial. AIM To determine the prevalence of H. pylori infection in esophageal carcinoma patients, we performed a retrospective observational study of esophageal tumors diagnosed in our hospital. METHODS We retrospectively reviewed the prevalence of H. pylori infection in a cohort of patients diagnosed with esophageal carcinoma. Concomitant or previous proton pump inhibitor (PPI) usage was also recorded. RESULTS A total of 89 patients with esophageal carcinoma (69 males, 77.5%), with a mean age of 66 years (range, 26-93 years) were included. AC was the most frequent pathological variant (n = 47, 52.8%), followed by squamous cell carcinoma (n = 37, 41.6%). Fourteen ACs (29.8%) originated in the gastroesophageal junction and 33 (70.2%) in the esophageal body. Overall, 54 patients (60.7%) presented at stages III and IV. Previous H. pylori infection occurred only in 4 patients (4.5%), 3 with AC (6.3% of all ACs) and 1 with squamous cell carcinoma (2.7% of all squamous cell tumors). All patients with previous H. pylori infection had stage III-IV. Only one patient had received prior H. pylori eradication therapy, whereas 86 (96.6%) had received previous or concomitant PPI treatment. CONCLUSION In our cohort of patients, and after histologic evaluation of paraffin-embedded primary tumors, we found a very low prevalence of previous H. pylori infection. We also reviewed the medical history of the patients, concluding that the majority had received or were on PPI treatment. The minimal prevalence of H. pylori infection found in this cohort of patients with esophageal carcinoma suggests a protective role.

Impact of definitive radiotherapy on metabolic response measured with 68Ga-PSMA-PET/CT in patients with intermediate-risk prostate cancer.

To assess the early metabolic response of the primary tumor using Gallium-68 (68Ga)-labeled-prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-PET/CT), as well as the relationship between PSMA change in the primary tumor and PSA response after definitive radiotherapy (RT), either alone or in combination with androgen deprivation therapy (ADT) in intermediate risk prostate cancer (IR-PCa) patients. The clinical data of 71 IR-PCa patients treated with RT alone (36 patients, 50.7%) or RT and ADT (35 patients, 49.3%) were retrospectively analyzed. The difference between pre- and Posttreatment primary tumor PSMA expression and serum PSA values measured 4 months after completion of treatment were compared between treatment arms. Correlation between primary tumor metabolic response and serum PSA changes was analyzed. The median duration between pre- and Posttreatment 68Ga-PSMA-PET/CT for the entire patient population was 6.9 months (range, 5.6-8.4 months), and it was similar in both treatment arms. A decrease in primary tumor maximum standardized uptake value (SUVmax) was seen in 66 patients (93.0%), with a median value of 61.2%, which is significantly lower in patients undergoing RT alone than those undergoing RT and ADT (45.1 ± 30.6% vs. 59.1 ± 24.7%; p = 0.004). The complete metabolic response rate was significantly higher in patients undergoing RT and ADT than those treated with RT alone (40% vs. 0%; p < 0.001). Although moderate and positive correlation between pretreatment SUVmax and oosttreatment SUVmax was observed, there was no significant correlation between SUV change and PSA change. For patients treated with RT and ADT, posttreatment SUVmax was significantly lower and SUV change was significantly higher in patients with PSA nadir than in those without. Our preliminary results show that RT, with or without ADT, significantly reduces primary tumor SUVmax and serum PSA levels. Nonetheless, our findings indicate that early treatment response using 68Ga-PSMA-PET/CT is not feasible for those treated with RT alone, and it may only be useful in better distinguishing patients with and without PSA nadir for those who received both RT and ADT.

TIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3

PurposeImmune checkpoint inhibitors have revolutionized the treatment of renal cell carcinoma (RCC), but many patients do not respond to therapy and the majority develop resistant disease over time. Thus, there is increasing need for alternative immunomodulating agents. The co-inhibitory molecule T-cell immunoglobulin and ITIM domain (TIGIT) may play a role in resistance to approved immune checkpoint inhibitors and is being investigated as a potential therapeutic target. The purpose of this study was to quantify TIGIT positivity in tumor-infiltrating T cells in RCC.MethodsWe employed tissue microarrays containing specimens from primary RCC tumors, adjacent normal renal tissue, and RCC metastases to quantify TIGIT within tumor-infiltrating CD3+ T cells using quantitative immunofluorescent analysis. We also compared these results to TIGIT+ CD3+ levels in four other tumor types (melanoma, non-small cell lung, cervical, and head and neck cancers).ResultsWe did not observe significant differences in TIGIT positivity between primary RCC tumors and patient-matched metastatic samples. We found that the degree of TIGIT positivity in RCC is comparable to that in lung cancer but lower than that in melanoma, cervical, and head and neck cancers. Correlation analysis comparing TIGIT positivity to previously published, patient-matched spatial proteomic data by our group revealed a negative association between TIGIT and the checkpoint proteins PD-1 and LAG3.ConclusionOur findings support careful evaluation of TIGIT expression on T cells in primary or metastatic RCC specimens for patients who may be treated with TIGIT-targeting antibodies, as increased TIGIT positivity might be associated with a greater likelihood of response to therapy.

Deciphering single-cell transcriptomic landscape of tumors in colorectal cancer treated with photothermal semiconducting polymers to design the combination therapy with checkpoint blockades for inhibition of tumor progression and metastasis

Immunotherapy is often less effective for tumors with “immune-excluded,” or “immune-desert” microenvironment. To circumvent this hurdle, new therapeutic strategies need to be designed to reprogram the tumor microenvironment (TME). It is well known that photothermal therapy (PTT) can prime the TME and provoke the systemic anti-tumor immunity. But few studies perform extensive exploration in depth to decipher the changes in TME after PTT with cutting-edge technology besides conventional flow cytometry analysis. In this study, we designed a nanosystem consisting of organic semiconductor polymer liposome nanoparticles (Y8 NPs) as a multimodal imaging and photothermal agent to image and treat tumors. Upon laser irradiation, Y8 NPs in tumors could rapidly increase the temperature, induce massive cancer cell apoptosis and also promote the immunogenic cell death (ICD), ultimately remodulating the TME. We employed single cell RNA sequencing (scRNA-seq) technology to comprehensively explore transcriptomic profiling of individual cells constituting TME, demonstrating heterogenous alterations in the subtypes of immune cells, even tumor cells. Considering the findings by scRNA-seq and TME remodulation, the combinational strategy with checkpoint blockade PD-1 antibody was designed to treat the tumors, demonstrating that the combination not only impedes primary tumor progression but also produce profound abscopal anti-tumor effect. In conclusion, we provide a simple strategy for the remodulation of TME with a photothermal nanosystem to achieve activation of anti-tumor immunity, and suppress primary and metastatic tumor progression.

The Role of Radiotherapy, Chemotherapy, and Targeted Therapies in Adult Intramedullary Spinal Cord Tumors

Intramedullary primary spinal cord tumors are rare in adults and their classification has recently evolved. Their treatment most frequently relies on maximal safe surgical resection. Herein, we review, in light of the WHO 2021 classification of central nervous system tumors, the knowledge regarding the role of radiotherapy and systemic treatments in spinal ependymomas, spinal astrocytomas (pilocytic astrocytoma, diffuse astrocytoma, spinal glioblastoma IDH wildtype, diffuse midline glioma H3-K27M altered, and high-grade astrocytoma with piloid features), neuro-glial tumors (ganglioglioma and diffuse leptomeningeal glioneuronal tumor), and hemangioblastomas. In spinal ependymomas, radiotherapy is recommended for incompletely resected grade 2 tumors, grade 3 tumors, and recurrent tumors not amenable to re-surgery. Chemotherapy is used in recurrent cases. In spinal astrocytomas, radiotherapy is recommended for incompletely resected grade 2 astrocytomas and grade 3 or 4 tumors as well as recurrent tumors. Chemotherapy is indicated for newly diagnosed high-grade astrocytomas and recurrent cases. In hemangioblastomas not amenable to surgery, radiotherapy is an effective alternative option. Targeted therapies are playing an increasingly important role in the management of some intramedullary primary spinal cord tumor subtypes. BRAF and/or MEK inhibitors have demonstrated efficacy in pilocytic astrocytomas and glioneuronal tumors, belzutifan in von Hippel–Lindau-related hemangioblastomas, and promising results have been reported with ONC201 in diffuse midline glioma H3-K27M altered.

Treatment of pediatric bone tumors around the knee

Primary bone tumors are rare but more frequently seen during childhood and with predilection for the distal femur and proximal tibia. Therapy of benign tumors-if indicated-includes surgical resection in most cases, whereas malignant bone tumors such as osteo- and Ewing's sarcomas are treated with chemotherapy, wide resection and/or radiation therapy (Ewing's sarcoma). The reconstruction of emerging bone defects is significantly influenced by surgeon-related preferences and tumor-associated factors, respectively. Double-barrel vascularized fibula grafts or extracorporeally irradiated autografts in combination with afree fibula transplant are preferred biological reconstruction techniques around the knee joint. In cases in which the knee joint cannot be preserved, reconstruction is performed using tumor endoprostheses, but potentially emerging leg length discrepancies after resection of apotent physis must be taken into account. In considerably young patients, rotationplasty might represent aviable option with promising functional results.

Interaction of ncRNAs and the PI3K/AKT/mTOR pathway: Implications for osteosarcoma

Abstract Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, and is characterized by high heterogeneity, high malignancy, easy metastasis, and poor prognosis. Recurrence, metastasis, and multidrug resistance are the main problems that limit the therapeutic effect and prognosis of OS. PI3K/AKT/mTOR signaling pathway is often abnormally activated in OS tissues and cells, which promotes the rapid development, metastasis, and drug sensitivity of OS. Emerging evidence has revealed new insights into tumorigenesis through the interaction between the PI3K/AKT/mTOR pathway and non-coding RNAs (ncRNAs). Therefore, we reviewed the interactions between the PI3K/AKT/mTOR pathway and ncRNAs and their implication in OS. These interactions have the potential to serve as cancer biomarkers and therapeutic targets in clinical applications.