Combined Modality Research Articles

Future perspectives of radiation therapy for Hodgkin Lymphoma: Risk-adapted, response-adapted, and safer than before.

Classical Hodgkin lymphoma is a lymphoproliferative disease with a good prognosis mainly seen in young people. Nevertheless secondary malignancy, cardiac disease and infertility may affect the long survivors with significant impact on quality of life, morbidity and overall survival. In the last decades several treatment strategies were evaluated to reduce the toxicity of first line treatment such as avoiding radiotherapy or its reduction in terms of dosage and extension. Many trials including interim Positron Emission Tomography evaluation fail to compare efficacy between combined modality treatment versus chemotherapy alone in particular in early stage disease. In this review we analyze which subset of patients could take advantage from proton therapy in terms of toxicity and cost effectiveness.

Revisiting Mac-2-Binding Protein Glycosylation Isomer (M2BPGi) for Diagnosing High-Risk Liver Fibrosis: A Stepwise Diagnostic Analysis

Abstract* Background The level of liver fibrosis is the basis for the treatment of chronic hepatitis B (CHB), and it is necessary to adapt non-invasive liver fibrosis modalities. We aimed to investigate the use of M2BPGi as a single or combined diagnostic modality for liver fibrosis in CHB patients through a stepwise diagnostic analysis. Methods Cross-sectional data were taken from patients between October 2021 and August 2022. Demographic data, blood profile, liver function, and liver stiffness were measured in CHB patients over 18 years old, willing to take part in the research, and had complete data. APRI, FIB-4, and AAR were calculated using the well-known formulas. Serum M2BPGi-levels were converted into a cut-off index (COI). The patients were divided into low-risk (LR) and high-risk fibrosis (HR) groups. A cut-off for each predictor variable to differentiate between the LR and HR groups was determined. The obtained cut-off was assessed for its association with the grouping of liver elastography results. Models to diagnose the liver stiffness measurement (LSM) ≥8 kPa were created and compared through multivariate and ROC analyses. Results The number of patients that met the inclusion and exclusion criteria was 143 (HR = 65, LR = 78). The cut-off for diagnosing LSM ≥8kPa was 0.311, 0.742, 0.635, and 1.434 for APRI, FIB-4, AAR, and M2BPGi, respectively. This cut-off was significantly associated with the results of the HR and LR groupings. A multivariate analysis found that FIB4, AAR, and M2BPGi added significantly to the model. Statistically, the most optimal use of M2BPGi was combined with FIB-4, with an AUC of 0.835. Conclusions The optimal cut-off of M2BPGi for diagnosing high-risk liver fibrosis in this study was 1.434. M2BPGi should be used with FIB-4 as a diagnostic tool for diagnosing liver fibrosis, especially in the absence of a liver biopsy or elastography.

Deep learning-powered multimodal biometric authentication: integrating dynamic signatures and facial data for enhanced online security

The significant increase in online activities in the wake of recent global events has underlined the importance of biometric person authentication on digital platforms. Although many biometric devices may be used for precise biometric authentication, acquiring the necessary technology, such as 3D sensors or fingerprint scanners, can be prohibitively expensive and logistically challenging. Addressing the demands of online environments, where access to specialized hardware is limited, this paper introduces an innovative approach. In this work, by fusing static and dynamic signature data with facial data captured through regular computer cameras, a dataset of 1750 samples from 25 individuals is constructed. Deep learning models, including convolutional neural networks (CNN), long short-term memory (LSTM), gated recurrent unit (GRU), and temporal convolutional networks (TCN), are employed to craft a robust multi-classification model. This integration of various deep learning algorithms has demonstrated remarkable performance enhancements in biometric authentication. This research also underscores the potential of merging dynamic and static biometric features, derived from readily available sources, to yield a high-performance recognition framework. As online interactions continue to expand, the combination of various biometric modalities holds potential for enhancing the security and usability of virtual environments.

Assessing the effectiveness of MRI, 18F-fluciclovine PET, SUVmax, and PSA in detecting local recurrence of prostate cancer after prostatectomy.

The primary objective of this study was to evaluate the discriminatory utility of magnetic resonance imaging (MRI), 18F-fluciclovine positron emission tomography (PET), maximum standardized uptake value (SUVmax), prostate-specific antigen (PSA), and combinations of these diagnostic modalities for detecting local prostate cancer recurrence in the setting of rising PSA after radical prostatectomy. Patients were characterised for clinical features such as Gleason score, PSA at surgery, PSA at follow-up, follow-up MRI result, follow-up PET result, follow-up SUVmax, and follow-up disease status. The utility of diagnostic parameters for detecting disease recurrence at the prostatectomy bed was assessed using receiver operating characteristics (ROC) analysis to determine the area under the curve (AUC) for each model. Sensitivity, specificity, and positive/negative predictive values were also calculated. Optimal cut-off points for continuous variables were determined based on maximum Youden's J statistics. The study found that MRI had the highest concordance (96%), sensitivity (100%), specificity (91%), positive predictive value (93%), and negative predictive value (100%) among the diagnostic modalities. The AUC for MRI was 0.9545, indicating a high discriminatory ability for detecting prostate cancer local recurrence. When combined, PET and SUVmax (cut-off value of 2.85) showed an improved performance compared to using them individually, with an AUC of 0.8925. The analysis suggests that MRI is the most effective imaging modality for detecting local prostate cancer recurrence, with 18F-fluciclovine PET and SUVmax also showing promising combined results. PSA has moderate discriminatory utility at follow-up but can still provide valuable information in detecting prostate cancer recurrence. Further research and recent references are needed to support these findings.

Orthosurgical treatment to obtain facial aesthetics

In the present case report, a 24-year-old male underwent a combined surgical and orthodontic treatment to enhance facial aesthetics. The treatment consisted of the use of an Edgewise fixed appliance (0.022 x 0.028-in), and was complemented by a mini Wing osteotomy. The results of the treatment improved facial contours, defining and elongating the submental area, and eliminating the adipose tissue. Orthodontically, the preservation of the canines and molars Class I relationship, and the maintenance of the compensatory projection of the lower incisors were observed. Satisfactory overbite and overjet were achieved, along with a levelled curve of Spee. The combined treatment modalities led to the achievement of functional occlusion and facial aesthetics.

Rapid Deposition of the Biomimetic Hydroxyapatite-Polydopamine-Amino Acid Composite Layers onto the Natural Enamel.

In this work, we developed a technology that enables rapid deposition of biomimetic composite films onto natural enamel slices (known as biotemplates). These films are composed of polydopamine (PDA) and nanocrystalline carbonate-substituted hydroxyapatite (nano-cHAp) that have been functionalized with amino acid l-Arginine. We utilized atomic force microscopy (AFM) and scattering scanning near-field optical microscopy (s-SNOM) combined with infrared (IR) synchrotron to achieve nanoscale spatial resolution for both IR absorption and topography analyses. This combined analytical modality allowed us to understand how morphology connects to local changes in the chemical environment on the biotemplate surface during the deposition of the bioinspired coating. Our findings revealed that when using the proposed technology and after the deposition of the first PDA layer, the film formed on the enamel surface nearly covers the entire surface of the specimen whose thickness is larger on the surface of the emerging enamel prisms. Calculation of the crystallinity index for the biomimetic layer showed a multiple increase compared with natural enamel. This indicates regular and dense aggregation of nano-cHAp into larger crystals, imitating the morphology of natural enamel rods. The microhardness of the formed PDA-based biomimetic layer mineralized with nano-cHAp functionalized with amino acid l-Arginine deposited on natural enamel was practically the same as that of natural enamel. The characterization of nano-cHAp-amino acid-PDA layers using IR and Raman microspectroscopy showed that l-arginine acts as a conjunction agent in the formation of mineralized biomimetic composite coatings. The uniformity of the mechanisms of PDA layer formation under different deposition conditions and substrate types allows for the formation of coatings regardless of the macro- and micromorphology of the template. Therefore, the results obtained in this work have a high potential for future clinical applications in dental practice.

Exploring contactless techniques in multimodal emotion recognition: insights into diverse applications, challenges, solutions, and prospects

In recent years, emotion recognition has received significant attention, presenting a plethora of opportunities for application in diverse fields such as human–computer interaction, psychology, and neuroscience, to name a few. Although unimodal emotion recognition methods offer certain benefits, they have limited ability to encompass the full spectrum of human emotional expression. In contrast, Multimodal Emotion Recognition (MER) delivers a more holistic and detailed insight into an individual's emotional state. However, existing multimodal data collection approaches utilizing contact-based devices hinder the effective deployment of this technology. We address this issue by examining the potential of contactless data collection techniques for MER. In our tertiary review study, we highlight the unaddressed gaps in the existing body of literature on MER. Through our rigorous analysis of MER studies, we identify the modalities, specific cues, open datasets with contactless cues, and unique modality combinations. This further leads us to the formulation of a comparative schema for mapping the MER requirements of a given scenario to a specific modality combination. Subsequently, we discuss the implementation of Contactless Multimodal Emotion Recognition (CMER) systems in diverse use cases with the help of the comparative schema which serves as an evaluation blueprint. Furthermore, this paper also explores ethical and privacy considerations concerning the employment of contactless MER and proposes the key principles for addressing ethical and privacy concerns. The paper further investigates the current challenges and future prospects in the field, offering recommendations for future research and development in CMER. Our study serves as a resource for researchers and practitioners in the field of emotion recognition, as well as those intrigued by the broader outcomes of this rapidly progressing technology.

A Review on the Design of Carbon-Based Nanomaterials as MRI Contrast Agents.

The administration of magnetic resonance imaging (MRI) contrast agents (CAs) has been conducted since 1988 by clinicians to enhance the clarity and interpretability of MR images. CAs based on gadolinium chelates are the clinical standard used worldwide for the diagnosis of various pathologies, such as the detection of brain lesions, the visualization of blood vessels, and the assessment of soft tissue disorders. However, due to ongoing concerns associated with the safety of gadolinium-based contrast agents, considerable efforts have been directed towards developing contrast agents with better relaxivities, reduced toxicity, and eventually combined therapeutic modalities. In this context, grafting (or encapsulating) paramagnetic metals or chelates onto (within) carbon-based nanoparticles is a straightforward approach enabling the production of contrast agents with high relaxivities while providing extensive tuneability regarding the functionalization of the nanoparticles. Here, we provide an overview of the parameters defining the efficacy of lanthanide-based contrast agents and the subsequent developments in the field of nanoparticular-based contrast agents incorporating paramagnetic species.

Abstract LB220: Farnesyltransferase inhibitors show synergistic anticancer effects in combination with novel KRAS G12C inhibitors

Abstract Background. Farnesyltransferase inhibitors (FTI) failed as monotherapies for various cancer types until the discovery of their potency in HRAS mutant human head and neck and bladder cancers. On the other hand, RAS mutant cancers have been a great challenge for cancer research until the discoveries and approvals of several KRAS-G12C allele specific inhibitors. However, G12C inhibitors were effective mainly in lung cancer and de novo and acquired resistance prompted the development of various combinational modalities including immunotherapy as well as SOS- and SHP2-inhibitors. Based on in-silico analysis of drug sensitivities of KRAS mutant cancer cell lines treated with various drugs including FTIs, we have explored the possibility of the combination of FTIs with KRAS inhibitors.Methods. Clinically approved farnesyl-transferase inhibitors (tipifarnib and lonafarnib) were combined with, novel KRAS G12C inhibitors (sotorasib and adagrasib) using human lung-, pancreatic and colorectal- adenocarcinoma cells in vitro and in vivo. Antitumoral effects were evaluated for cell proliferation, apoptosis and migratory activity. Mechanisms of action were investigated by immunoblot analyzes of various farnesylated proteins, RAS activation and signaling, videomicroscopy and also by histopathology of xenograft tumors. Results. Synergistic anticancer effects were observed upon the combination of FTIs with G12C inhibitors in KRAS G12C mutant human cancer cell lines in vitro. We found that the combination interfered with the compensatory re-activation of HRAS, farnesylation of RHEB in the PI3K/mTOR pathway and lamin. Furthermore, we observed enhanced efficacy of sotorasib upon combination with tipifarnib in the xenograft models of lung adenocarcinoma affecting mitotic- and apoptotic rates and inducing necrosis.Discussion. Our findings suggest the potential clinical applicability of the combination of KRAS-G12C inhibitors and farnesyl-transferase inhibitors. Furthermore, our preliminary data suggest that the synergistic effect of FTIs on KRAS-G12C inhibitors can be projected to G12D inhibitors as well. Citation Format: Jozsef Timar, Marcell Baranyi, Eszter Molnar, Ivan Randelovic, Mihaly Cserepes, Jozsef Tovari, Balazs Hegedus. Farnesyltransferase inhibitors show synergistic anticancer effects in combination with novel KRAS G12C inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB220.

Targeted interleukin-2 enhances the in vivo anti-cancer activity of Pluvicto™.

Pluvicto™ ([177Lu]Lu-PSMA-617), a radioligand therapeutic targeting prostate-specific membrane antigen (PSMA), has been recently approved for the treatment of metastatic castration-resistant prostate cancer (mCRPR). The drug suffers from salivary gland and kidney uptake that prevents its dose escalation to potentially curative doses. In this work, we sought to potentiate the in vivo anti-cancer activity of Pluvicto™ by combining it with L19-IL2, a clinical-stage investigational medicinal product based on tumor-targeted interleukin-2. We established a new PSMA-expressing model (HT-1080.hPSMA) and validated it using a fluoresceine analogue of PSMA-617 (compound 1). The HT-1080.hPSMA model was used to study the saturation and tumor retention of Pluvicto™ (compound 2) and to run combination therapy studies with L19-IL2. To complement our understanding of the mechanism of action of this novel combination, we conducted proteomics experiments on tumor samples after therapy with Pluvicto™ alone or in combination with the immunocytokine. High, selective, and long-lived tumor uptake was observed for Pluvicto™ (2) in the novel HT-1080.hPSMA model. Therapy studies in HT-1080.hPSMA tumor-bearing mice revealed that the combination of Pluvicto™ (2) plus L19-IL2 mediated curative and durable responses in all animals. Potent in vivo anti-cancer activity was observed solely for the combination modality, at doses that were well tolerated by treated animals. Proteomics studies indicated that L19-IL2 boosts the activation of the immune system in animals pre-treated with Pluvicto™. The therapeutic efficacy of Pluvicto™ at low radioactive doses can be effectively enhanced by the combination with L19-IL2. Our findings warrant further clinical exploration of this novel combination modality.

Emotional analysis of joint sports quality expansion tasks based on multi-modal feature fusion

A multi-modal feature based motion emotion analysis model based on a fusion deep learning model is proposed for the problem of analyzing the motion emotions of participants in the joint exercise quality expansion task. This model involves three major modalities: EEG signals, peripheral physiological signals, and facial expression signals, and processes and fuses the information of these three main modalities to achieve the effect of processing multi-dimensional motor emotional information. At the same time, this study introduces the design concept of residual networks, using self attention modules and multi head mutual attention modules to process different modal features. The results showed that the combination of peripheral physiological modality and facial expression modality had the highest accuracy among the three modality combinations, with an accuracy rate of 88.8 %. The feature fusion method based on the cascaded residual attention mechanism module has better accuracy and F1 Score performance than other methods. In addition, different emotional states can be effectively identified and distinguished in these three modalities, indicating that the model has a wide range of possibilities in practical applications.

Revisiting Combined Modality Therapy in Older Patients With Luminal Breast Cancer Through the Patient Lens.

Revisiting Combined Modality Therapy in Older Patients With Luminal Breast Cancer Through the Patient Lens.

Nasal cavity extramedullary plasmacytoma: literature review and clinical experience

Abstract BACKGROUND. Extramedullary plasmacytoma is an extremely rare solitary plasma cell neoplasm that occurs in locations other than bone, without involving the bone marrow. It is commonly located in the upper aerodigestive tract. In the head and neck region, the most frequent location is the sinonasal region. MATERIAL AND METHODS. A systemic review in accordance with the PRISMA guidelines was done with research works in PubMed, Elsevier database, Cochrane library, Web of Science, Scopus, Crossref and Google Scholar. The search was carried out using the keywords “plasmacytoma and nose”, “extramedullary plasmacytoma”, “extramedullary plasmacytoma of nose”, “plasmacytoma and nasal cavity”, and “extramedullary plasmacytoma of nasal cavity”. RESULTS. We analysed 27 research works with a total number of 32 cases. The most common presenting symptoms were nasal cavity bleeding. The disease showed a male preponderance (78.1%). Bone erosion was seen in 7 cases. The histopathological examination showed plasma cells arranged predominantly as a uniform population or sheet-like appearance. A common immunohistochemical marker was CD138 (11 cases). Treatment was primarily radiotherapy (43.7%). We are also reporting a case of a 53-year-old male with plasmacytoma of the middle turbinate managed by wide resection and postoperative radiotherapy. CONCLUSION. Though a less common condition, in a case of polypoidal-like lesion with bleeding tendency, the clinician should keep in mind the possibility of extramedullary plasmacytoma. The diagnosis is made with histopathological examination and immunohisto-chemistry of the tissue involved. Treatment can be radiotherapy, surgery, or a combination of modalities.

Outcomes of the transformation of follicular lymphoma to diffuse large B-cell lymphoma in the rituximab era: A population-based study.

Histological transformation (HT) to diffuse large B-cell lymphoma (DLBCL) is a common complication of follicular lymphoma (FL) and is usually associated with a dismal outcome. However, the survival rate of these patients has improved over the last 20 years with the introduction of rituximab. This study aimed to access the outcome of transformation to DLBCL (t-DLBCL) from FL in a retrospective series that began after the widespread use of rituximab use. In addition, we also compared survival between t-DLBCL and primary DLBCL (p-DLBCL) in the same timeframe. We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify patients with primary FL and patients with p-DLBCL between 2000 and 2020. Patients who had a subsequent diagnosis of DLBCL at least 2 months after FL diagnosis were identified as t-DLBCL. Finally, we identified 50,332 FL and 95,933 p-DLBCL. With a median follow-up of 119 months, 1631 patients developed t-DLBCL. The median time from FL diagnosis to t-DLBCL was approximately 4 years. The post-transformation survival (PTS) rate at 5 years was 49.6%, with a median PTS of 56 months. Older age, advanced stage, and early transformation were associated with worse PTS. Furthermore, t-DLBCL receiving chemotherapy or combined modality as initial therapy before HT was also associated with worse PTS, while the result was inverse when taking the impact of initial management strategy at HT into account. Taking t-DLBCL and p-DLBCL as a whole, comparable survival was observed between p-DLBCL and t-DLBCL receiving radiation or watch-and-wait as initial therapy prior to HT. The outcome of t-DLBCL in the rituximab era was better than historical series before the rituximab era. Due to the good prognosis, we did not recommend autologous stem cell transplantation for t-DLBCL receiving watch-and-wait or radiation as initial therapy before HT.

Alcohol Use Disorder and Depression: The Complexity of Comorbidity

IntroductionAlcohol Use Disorder (AUD) and depression are among the most prevalent mental health concerns on a global scale. The co-occurrence of alcohol use disorder (AUD) and depression has been well acknowledged, leading to intricate issues in diagnosis, treatment, and prognosis.ObjectivesThis study aims to analyse the complex correlation between AUD (Alcohol Use Disorder) and depression, with a specific emphasis on examining common underlying causes, reciprocal influences, and potential implications for clinical treatment.MethodsAn exhaustive review of literature was undertaken, emphasizing epidemiological studies, neurobiological research, and the efficacy of combined treatment modalities. The review also delved into the potential role of genetics, environmental factors, and psychosocial stressors in co-occurrence.ResultsThe available evidence indicates that there exists a reciprocal relationship between depression and alcohol use disorder (AUD), wherein each disease can serve as a triggering factor for the other. This interplay between depression and AUD forms a detrimental cycle that intensifies the severity of both conditions. The comorbidity of various disorders may be attributed to the presence of shared neurochemical pathways, with a particular emphasis on the serotonin system. Furthermore, the co-occurrence of both illnesses frequently leads to heightened symptom severity, reduced treatment efficacy, and a higher risk of suicide.ConclusionsThe complex relationship between alcohol use disorder (AUD) and depression underscores the need for a comprehensive and integrated therapy strategy. The effective management of this comorbidity necessitates the implementation of multidisciplinary collaboration, patient education, and early intervention.Disclosure of InterestNone Declared

Current Concepts for the Treatment of Peri-implant Disease.

Peri-implant diseases are defined as bacterial plaque-induced inflammatory conditions affecting implant-surrounding tissues and are classified as peri-implant mucositis and peri-implantitis. Peri-implant mucositis is characterized by an inflammatory lesion that resides in the soft tissue compartment, whereas at peri-implantitis sites the lesions also feature progressive loss of implant-supporting bone. Inflammation resolution and disease progression arrestment are the main therapeutic endpoints of the treatment of peri-implant diseases. The present position paper displays the current evidence and clinical recommendations of the European Association for Osseointegration for the treatment of peri-implant diseases. Mechanical biofilm removal along with the reinforcement of patient-administered oral hygiene is considered the standard treatment for managing peri-implant mucositis. It is recommended to assess the outcomes of peri-implant mucositis treatment 2 to 3 months after therapy, and repeated intervention should be considered in the absence of treatment success. Peri-implantitis treatment should follow a stepwise treatment approach, starting with nonsurgical treatment followed by surgical intervention, if that is not sufficient. Surgical peri-implantitis therapies include nonreconstructive, reconstructive, and combined treatment modalities. Implantoplasty may be advocated for the treatment of supracrestal peri-implant defects, whereas reconstructive therapy is indicated at peri-implantitis sites featuring intraosseous defects with a depth ≥ 3 mm. Adjunctive reconstructive measures may be beneficial in enhancing radiographic defect fill and maintaining postoperative soft tissue levels, which may have a great impact in esthetic cases. The adjunctive use of systemic antibiotics during surgical therapy does not seem to improve the clinical outcomes. Regular supportive peri-implant therapy with biofilm removal should be an integral part of the treatment protocol for peri-implant diseases. In the presence of advanced bone loss around implants that do not play a strategic role in masticatory function, implant removal may be considered immediately.

Involved-site Radiation Therapy is Equally Effective and Less Toxic Than Involved-field Radiation Therapy in Patients Receiving Combined Modality Treatment for Early-stage Unfavorable Hodgkin Lymphoma—An Analysis of the Randomized Phase 3 HD17 Trial of the German Hodgkin Study Group

PurposeCombined modality treatment (CMT) with chemotherapy followed by consolidation radiotherapy (RT), provides excellent outcomes for patients with early-stage Hodgkin lymphoma (HL). The international standard of care for consolidation RT, involved-site/involved-node radiotherapy (ISRT/INRT), has never been evaluated in a randomized phase III trial against the former standard involved-field radiotherapy (IFRT). Methods and materialsIn the multicenter phase III AnonymizedStudyGroupXXX AnonymizedStudyYYY trial, patients with early stage unfavorable HL were randomized between the standard CMT group and a positron-emission tomography (PET) -guided group. In the standard group, patients received two cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) and two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gray (Gy) IFRT. In the experimental group patients received no further therapy if post-chemotherapy PET was negative, and 30 Gy AnonymizedStudyGroupXXX -INRT, comparable and therefore termed here ISRT, if PET was positive. Here, we analyze the interim PET positive patients in a post hoc analysis, and therefore the randomized comparison of IFRT versus INRT/ISRT. Results1,100 patients were randomized, of which 311 had a positive PET after chemotherapy. Kaplan-Meier estimates of 4-year progression-free survival (PFS) were 96.8 % (95% CI: 91.6% – 98.8%) in the IFRT group and 95.4% (95% CI: 89.9% – 97.9%; HR: 1.40, 95% CI: 0.44 – 4.42) in the ISRT group. Pattern of recurrence analyses indicated that none of the cases of disease progression or recurrence in the ISRT group would have been prevented by the use of IFRT. Acute grade III/IV toxicities occurred in 8.5% of IFRT patients and 2.6% of ISRT patients (p=0.03). ConclusionsFor the first time, consolidation INRT/ISRT was randomly compared to IFRT in a phase III trial. Regarding PFS, no advantage for IFRT could be demonstrated. In summary, our data confirm the place of INRT/ISRT as the current standard of care.

P53-Armed Oncolytic Virotherapy Improves Radiosensitivity in Soft-Tissue Sarcoma by Suppressing BCL-xL Expression.

Soft-tissue sarcoma (STS) is a heterogeneous group of rare tumors originating predominantly from the embryonic mesoderm. Despite the development of combined modalities including radiotherapy, STSs are often refractory to antitumor modalities, and novel strategies that improve the prognosis of STS patients are needed. We previously demonstrated the therapeutic potential of two telomerase-specific replication-competent oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in human STS cells. Here, we demonstrate in vitro and in vivo antitumor effects of OBP-702 in combination with ionizing radiation against human STS cells (HT1080, NMS-2, SYO-1). OBP-702 synergistically promoted the antitumor effect of ionizing radiation in the STS cells by suppressing the expression of B-cell lymphoma-X large (BCL-xL) and enhancing ionizing radiation-induced apoptosis. The in vivo experiments demonstrated that this combination therapy significantly suppressed STS tumors' growth. Our results suggest that OBP-702 is a promising antitumor reagent for promoting the radiosensitivity of STS tumors.

Demographic Variations and Time to Initiation of Adjunct Treatment following Surgical Resection of Anaplastic Astrocytoma in the United States—A National Cancer Database Analysis

INTRODUCTION: Anaplastic Astrocytoma (AA) is a rare primary brain tumor with a significant variation in the type and timing of adjunct treatment (AT) following the surgical resection. METHODS: The National Cancer Database (NCDB) was queried for patients diagnosed with AA from 2004 to 2016. Cox proportional hazards and modeling was used to determine factors influencing survival, including the impact of time to initiation (TTI) of adjuvant therapy. RESULTS: Overall, 5890 patients were identified from the database. The use of combined RT+CT temporally increased from 66.3% (2004-2007) to 79% (2014-2016), p < 0001. Patients more likely to receive no treatment following surgical resection included elderly (>60 years old), hispanic patients, those with either no or government insurance, those living >20 miles from the cancer facility, those treated at low volume centers (<2 cases/year). AT was received following surgical resection within 0-4 weeks, 4.1-8 weeks, and >8 weeks in 41%, 48%, and 3%, respectively. Compared to patients who received RT + CT, patients were likely to receive RT only as AT either at 4-8 weeks or >8 weeks after the surgical procedure. Patients who received AT within 0-4 weeks had the 3-year OS of 46% compared to 56.7% for patients who received treatment at 4.1-8 weeks. CONCLUSIONS: Across the cohort, nearly 15% of patients received no AT following surgery, with the proportion of patients receiving no AT generally decreasing over time. This decrease corresponds to increased utilization of combined modality AT during the same time span. The highest utilization of combined AT within this cohort was between 4.1-8 weeks following the surgery.

Update on FDG-PET in pediatric lymphoma.

Lymphoma represent the third most common malignant disease in childhood and adolescence. They are divided into pediatric Hodgkin lymphoma (P-HL) and pediatric non-Hodgkin lymphoma (P-NHL). In P-HL, excellent cure rates are achieved through combined modality treatment using chemotherapy and radiotherapy. For more than 20 years, FDG-PET has been an integral part of the treatment and guides its intensity through improved staging and precise assessment of chemotherapy response. In P-NHL, good cure rates are achieved with chemotherapy alone. At present FDG-PET plays only a subordinate role in the treatment setting. Its potential to contribute to treatment management is far from being fully utilised. In this article, the current status of FDG-PET in pediatric lymphoma is presented in detail. The core elements are the sections on staging and response assessment. In addition, challenges and pitfalls are discussed and future developments are outlined.