Treatment Of Localized Tumors Research Articles

Treatment of Pediatric, Adolescent, and Young Adult Patients With Fusion-Positive Alveolar Rhabdomyosarcoma Infiltrating Regional Lymph Nodes in the European CWS-2002P and RMS 2005 Studies and the Soft Tissue Sarcoma Registry.

Patients with alveolar rhabdomyosarcoma (ARMS) with regional lymph node involvement (N1) are defined as "very-high-risk rhabdomyosarcoma" in Europe. Different chemotherapy regimens were used in European study protocols. Patients with FOXO1 fusion-positive N1 ARMS registered in the CWS-2002P study, the EpSSG RMS 2005 study, and SoTiSaR were retrospectively investigated. Patients received systemic treatment with chemotherapy (CHT) and local treatment of primary tumor (PT) and involved lymph nodes (LN) with radiotherapy (RT) and/or surgery. Kaplan-Meier estimators and Cox regression were used to examine event-free survival (EFS) and overall survival (OS) according to prognostic factors and treatment. A total of 156 patients registered in RMS 2005 (n = 99), CWS-2002P (n = 20), and SoTiSaR (n = 37) between 2003 and 2020 were eligible for this analysis. Median age at diagnosis was 10.2years [0.1-21.9]. Treatment comprised CHT with IVADo (ifosfamide, vincristine, actinomycin-D, doxorubicin, n = 93; 60%), VAIA (vincristine, actinomycin-D, ifosfamide, adriamycin/doxorubicin, n = 53; 34%) or other regimens (n = 10; 6%); resection of the PT (n = 89; 57%), LN sampling or dissection (n = 92; 59%), and/or RT (n = 139; 89%). Maintenance treatment (MT) was added in n = 99/135 (73%) patients who achieved complete remission. Five-year EFS and OS of the cohort were 45% and 47%, respectively. Age and tumor size were independent prognostic factors for EFS. Local treatment applied to the LN with surgery, RT or both significantly improved EFS (p = 0.02) and OS (p = 0.04), with no difference between the modalities (p = 0.7). Patients with fusion-positive N1 ARMS carry a poor prognosis. Adequate local treatment of LN improved survival.

Radioresistance-related gene signatures identified by transcriptomics characterize the prognosis and immune landscape of pancreatic cancer patients

BackgroundRadiotherapy (RT) is an important means of local treatment of solid tumors, and radioresistance is the main reason for RT failure for tumors, especially pancreatic cancer (PC). It is urgent to distinguish key genes and mechanisms of radioresistance in PC.MethodsWe acquired the data from The Cancer Genome Atlas (TCGA), obtained the gene modules associated with radioresistance by weighted gene coexpression network analysis (WGCNA), and identified differentially expressed genes (DEGs) between normal and tumor samples. Radioresistance-related genes (RRRGs) were determined with the intersection of WGCNA and DEGs. The hub RRRGs associated with prognosis were distinguished by the least absolute shrinkage and selection operator (LASSO) regression. We established a risk score model using multivariate Cox regression. Immune cell infiltration and drug sensitivity were evaluated through the CIBERSORT algorithm and the “OncoPredict” software package, respectively. The association of the key gene RIC3 and PC clinical features was verified in public databases, and its biological behaviors were explored in vitro.ResultsThe intersection of DEGs and WGCNA confirmed 14 RRRGs, then six hub RRRGs were identified using LASSO. A key four genes (DUSP4, ADORA2B, SCGB2A1, and RIC3) risk score model was constructed and proved to be capable of independently estimating the prognosis of PC. There is no significant difference between risk score groups in various immune cell infiltration and response to immunotherapy. Although the low-risk group seemed to exhibit greater sensitivity to antitumor drugs, the four drugs (5-fluorouracil [5-FU], leucovorin, irinotecan, and oxaliplatin) currently used for PC patients had no statistical difference for the low- and high- group. The overexpression of RIC3 had a synergy effect with irradiation on inhibited malignant biological properties of PC cells, which was verified by detecting the proliferation ability, apoptosis rate, cell cycle distribution, and migration ability of PANC-1 cells.ConclusionsWe herein presented signature genes correlated with radioresistance in PC and established a risk score model competent in estimating patients’ clinical outcomes and response to antitumor drugs. The above evidence could contribute to comprehending the mechanisms of radioresistance and identifying the underlying therapy targeting.

Ultrasound-Induced Stable and Inertial Cavitation of Magnetic Nanoparticles for Drug Delivery Applications

Abstract Drug-loaded magnetic nanoparticles (MNPs) accumulated by an external magnetic field already showed their efficacy in localized tumor treatment in animal studies. Furthermore, specific MNPs are sonosensitive, enabling them to generate inertial cavitation when exposed to a focused ultrasound field. This can be used for controlling drug release, as well as for particle detection and mapping. In addition to inertial cavitation, stable cavitation is also a part of the cavitation process, which has not yet been evaluated on MNPs. While stable cavitation is less harmful to surrounding tissue compared to inertial cavitation, it also contributes to enhanced tumor perfusion. Hence, an optimal strategy could involve inducing inertial cavitation only within the tumor region for drug release and mapping, while employing stable cavitation outside the tumor to enhance perfusion. This study aims to investigate stable cavitation mediated by MNPs for the first time, while examining their overall cavitation behavior.

Local Endoscopic Treatment of Low-Grade Urothelial Tumors in the Upper Urinary Tract-Oncological Outcome of a Consecutive Single-Center Series of 118 Patients.

Upper urinary tract urothelial tumors are mostly treated with the use of endoscopic laser ablation. The treatment is recommended when the tumor is low grade and non-invasive. The aim of the present study was to investigate the oncological outcome of patients treated endoscopically for low-grade (LG) upper tract urothelial carcinoma (UTUC). One hundred and eighteen consecutive patients with pTa LG UTUC initially treated with laser ablation from 2012-2022 at a single university hospital were included. Patient and tumor characteristics, treatment, and oncological outcomes were retrospectively registered from electronic medical journals. Survival analysis was performed using Kaplan-Meier and Nelson-Aalen plots. The median number of local recurrences was 2 with a median time to first recurrence of 5 months (IQR: 2-46). The 2-year share of patients having no recurrence was 28.8%. The risk of recurrence was highest within the first 3 years following initial treatment. Two-year survival function with no progression and preserved renal unit was 67.9%. The two-year overall survival (OS) and disease-specific survival (DSS) were 84.2% and 97.1%. The 5-year OS and DSS were 59.1% and 94.1%. The median follow-up time for OS was 36 months (IQR: 20.3-58.8). In the patient series, we found that the risk of recurrence following laser ablation of LG UTUC was high; however, it was associated with a low risk of progression and high OS and DSS. Therefore, we conclude that treatment with laser ablation in patients with LG UTUC is safe, although frequent follow-up is needed to detect recurrence.

Imageable Brachytherapy with Chelator-Free Radiolabeling Hydrogel.

Brachytherapy stands as an essential clinical approach for combating locally advanced tumors. Here, an injectable brachytherapy hydrogel is developed for the treatment of both local and metastatic tumor. Fe-tannins nanoparticles are efficiently and stably radiolabeled with clinical used therapeutic radionuclides (such as 131I, 90Y, 177Lu, and 225Ac) without a chelator, and then chemically cross-linked with 4-armPEG-SH to form brachytherapy hydrogel. Upon intratumoral administration, magnetic resonance imaging (MRI) signal from ferric ions embedded within the hydrogel directly correlates with the retention dosage of radionuclides, which can real-time monitor radionuclides emitting short-range rays in vivo without penetration limitation during brachytherapy. The hydrogel's design ensures the long-term tumor retention of therapeutic radionuclides, leading to the effective eradication of local tumor. Furthermore, the radiolabeled hydrogel is integrated with an adjuvant to synergize with immune checkpoint blocking therapy, thereby activating potent anti-tumor immune responses and inhibiting metastatic tumor growth. Therefore, this work presents an imageable brachytherapy hydrogel for real-time monitoring therapeutic process, and expands the indications of brachytherapy from treatment of localized tumors to metastatic tumors.

Priming of cancer-immunity cycle by alleviating hypoxia-induced ferroptosis resistance and immunosuppression

Stimulating a robust cancer-immunity cycle (CIC) holds promising potential for eliciting potent and enduring immune responses for cancer immunotherapy. However, designing a therapeutic nanomaterial capable of both enhancing tumor immunogenicity and mitigating immunosuppression is challenging and often associated with complicated design paradigms and immune-related adverse effects. Herein, a multienzyme-mimetic alloy nanosheet incorporating palladium (Pd) and iron (Fe) is developed, which can prime effective CIC by overcoming ferroptosis resistance for enhancing tumor immunogenicity and reprograming the tumor microenvironment for enhanced second near-infrared (NIR-II) photoimmunotherapy. The nanosheets accumulate in tumors when administered intravenously and counteract hypoxia through catalase-like oxygen production and subsequent reduction of hypoxia-inducible factor-1α, M2-like macrophages, regulatory T-cell, and programmed death-ligand 1 (PD-L1) expression. The surface plasmon resonance of the nanosheets enables NIR-II phototherapy and photoacoustic imaging, coupling with its ferroptosis and tumor microenvironment reprogram properties to synergize with anti-PD-L1 checkpoint blockade therapy to achieve satisfactory antitumor outcome. This study offers a strategy for localized tumor treatment and boosting the CIC through a straightforward and inexpensive nanomaterial design.

Comparing open and robot-assisted partial nephrectomy – a single institution report

BackgroundOpen partial nephrectomy (OPN) has previously been considered the gold standard procedure for treatment of T1 localized renal tumors. After introduction of robot assisted partial nephrectomy (RAPN) as an alternative method to OPN, OPN was gradually abandoned at our department. The aim of the study was to retrospectively compare the results of patients treated with either OPN or RAPN for suspected renal carcinoma.MethodsPatients who underwent either open or robotic assisted partial nephrectomy between January 1st 2010 and December 31st 2020 were retrospectively included in the study. Each tumor subjected to surgery was scored preoperatively by the RENAL nephrometry score. Complications within 30 days were assessed according to the Clavien-Dindo classification system.ResultsA total of 197 patients who underwent partial nephrectomy were identified; 75 were subjected to OPN and 122 were treated with RAPN. There were no significant differences between the groups with respect to age (OPN: 63 years ± 11, RAPN: 62 years ± 10), gender (OPN: 71/29%, RAPN: 67/33%), body mass index (OPN: 28 ± 5, RAPN: 28 ± 5), ASA score (OPN: 2.4 ± 0.6, RAPN: 2.2 ± 0.5), or nephrometry score (OPN: 6.6 ± 1.7, RAPN: 6.9 ± 1.7, p = 0.2). The operative time was significantly shorter in the OPN group (81 min) compared to the RAPN group (144.5 min, p < 0.001). Mean perioperative blood loss was 227 ± 162 ml in the OPN group compared to 189 ± 152 ml in the RAPN group (p = 0.1). Mean length of stay was shorter in the RAPN group (3 days) compared to the OPN group (6, days, p < 0.001). Positive surgical margin rate was significantly higher in the OPN group (21.6%) compared to the RAPN group (4.2%, p < 0.001). There were no differences in the number of Clavien-Dindo graded complications between the groups (p = 0.6).ConclusionsThe introduction of RAPN at our department resulted in shorter length of stay and fewer positive surgical margins, without increasing complications.

Outcomes with non-small cell lung cancer and brain-only metastasis

BackgroundWe evaluated outcomes in non-small cell lung cancer (NSCLC) patients who presented with brain-only metastatic (BOM) disease overall and by EGFR/ALK mutation status. MethodsWe analyzed clinico-demographic, treatment and survival data for all NSCLC patients who presented to our center between 2014 and 2016 with BOM as their first presentation of metastatic disease. Differences in overall survival (OS) were evaluated using log-rank tests for NSCLC wildtype (NSCLCwt) versus NSCLC with an ALK-rearrangement/EGFR-mutation (NSCLCmut+). ResultsOf 109 patients with BOM, median age was 68 years; 51 % were female; 69 % Caucasian; 76 % ever-smoker; 76 % adenocarcinoma; and 25 % NSCLCmut+. While 41 patients (38 %) had subsequent brain-only progressive disease (PD), 22 (20 %) developed extracranial metastases. A higher proportion of NSCLCmut+ (vs –wt) subsequently progressed outside the brain (37 % vs 15 %, p = 0.03). Median time-to-first-extracranial-metastases was 8.5 (NSCLCmut+) vs 21.0 months (NSCLCwt; p = 0.23).With 17.7 months median follow-up, median-OS was 15.9 months [95%CI: 11.5–21.3; all patients]; 12.3 [7.4–18.4; NSCLCwt] and 38.9 [21.3-not reached (NR); NSCLCmut+] (p = 0.09). In 33 of 80 patients with de novo BOM, the primary tumor was treated with surgery or radiotherapy. In patients with NSCLCwt, there was no OS benefit associated with local lung tumor treatment (p = 0.68), whereas in NSCLCmut + pts, local lung tumor treatment correlated with greater OS (median-OS NR vs 21.5 months; p = 0.05). ConclusionIn patients with NSCLCwt with BOM, we observed a -predominant pattern of brain-only secondary progression, however patients with NSCLCmut + more often progressed extracranially. In patients with NSCLCmut+ and BOM, definitive primary tumor treatment correlated with improved survival.

Comparative effectiveness of frame-based and mask-based Gamma Knife stereotactic radiosurgery in brain metastases: A 509 patient meta-analysis.

Stereotactic Radiosurgery (SRS) is the primary treatment for patients with limited numbers of small brain metastases. Head fixation is usually performed with framed-based (FB) fixation; however, mask-based (MB) fixation has emerged as a less invasive alternative. A comparative meta-analysis between both approaches has not been performed. Databases were searched until August 28th, 2023, to identify studies comparing MB and FB SRS in the treatment of brain metastases. Our outcomes of interest included local tumor control (LTC), radiation necrosis (RN), mortality, and treatment time (TT). Mean difference (MD), risk ratio (RR), and hazard ratio (HR) were used for statistical comparisons. From 295 articles initially identified, six studies (1 clinical trial) involving 509 patients were included. LTC revealed comparable RR at 6-months (RR = 0.95[95%CI = 0.89-1.01], p = 0.12) and a marginal benefit in FB SRS at 1-year (RR = 0.87[95%CI = 0.78-0.96], p = 0.005). However, in oligometastases exclusively treated with single-fraction SRS, LTC was similar among groups (RR = 0.92 [95%CI = 0.89-1.0], p = 0.30). Similarly, in patients with oligometastases treated with single-fraction SRS, RN (HR = 1.69; 95%CI = 0.72-3.97, p = 0.22), TT (MD = -29.64; 95%CI = -80.38-21.10, p = 0.25), and mortality were similar among groups (RR = 0.62; 95%CI = 0.22-1.76, p = 0.37). Our findings suggest that FB and MB SRS, particularly oligometastases treated with single-fraction, are comparable in terms of LTC, RN, TT, and mortality. Further research is essential to draw definitive conclusions.

Tumor Microenvironment Reprogrammed Bimetallic Hybrid Nanostimulator for Triggering Radio-Cuproptosis-Immunotherapy.

Radio-immunotherapy driven by radiation-induced immunogenic cell death (ICD) is emerging as a potential opportunity to address conventional radiotherapy (RT) that is only applicable to localized tumor treatment. However, the effective activation of ICD during RT is severely limited by radiation dose, weak tumor immunogenicity, and radio-resistance caused by tumor microenvironment (TME). Herein, a novel bimetallic hybrid nanoscale coordination nanostimulator is first proposed by phosphate backbone doped with copper ions (Cu2+) and hafnium ions (Hf4+), and then modified with polyvinylpyrrolidone (PVP). The PVPylated Cu/Hf-doped phosphate nanostimulator (denoted as CHP) exhibits effective reprogramming of TME, including depletion of tumor endogenous glutathione (GSH), relief of tumor hypoxia and repolarization of M2 phenotypic macrophages, thus achieving tumor radiosensitization at low X-ray irradiation dose, gradually accumulation of tumor endogenous reactive oxygen species (ROS) and augmenting cuproptosis. In addition, cuproptosis can amplify RT-induced anti-tumor immunity through ICD activation, ultimately resulting in a robust anti-tumor immune response and long-term immunity, evidenced by distant tumor growth inhibition of 4T1-tumor-bearing models. More interestingly, it is discovered that CHP-mediated cuproptosis can be intensifiable during X-ray irradiation. Taken together, this work presents a novel radio-cuproptosis-immunotherapy cascade strategy, offering a new perspective for innovation in the treatment field of breast cancer.

Chemotherapy Release From Bortezomib-Impregnated Polymethylmethacrylate-Coated Intramedullary Nails: A Novel In Vitro Study for a Local Chemotherapy Delivery Device.

Bortezomib (BAN) is a proteasome inhibitor approved for the treatment of multiple myeloma and lymphoma. Despite its efficacy in various tumor models, systemic administration can result in toxicity to healthy organs. The purpose of this study is to evaluate the elution profile of BAN from PMMA cement for the local treatment of orthopedic tumors. BAN solution (5 mg; 2 mg/mL) was mixed with Simplex cement (40 g, Stryker), followed by injection of cement into an antibiotic cement nail mold (13 mm) to coat a 10 mm titanium femoral nail (DePuy Synthes). Once the cement polymerized, the nail was cut into 2 cm segments for the BAN elution study. There is a sustained release of BAN for up to 28 days. The overall concentration of BAN released at each time point was between 74 and 263 ng/ml, which is compatible with the peak blood concentration of a single intravenous BAN injection. This study demonstrates the feasibility of using PMMA bone cement as a local BAN delivery tool, essential for future studies and treatment targeting multiple myeloma cells.

Advances in Hydrogels of Drug Delivery Systems for the Local Treatment of Brain Tumors.

The management of brain tumors presents numerous challenges, despite the employment of multimodal therapies including surgical intervention, radiotherapy, chemotherapy, and immunotherapy. Owing to the distinct location of brain tumors and the presence of the blood-brain barrier (BBB), these tumors exhibit considerable heterogeneity and invasiveness at the histological level. Recent advancements in hydrogel research for the local treatment of brain tumors have sought to overcome the primary challenge of delivering therapeutics past the BBB, thereby ensuring efficient accumulation within brain tumor tissues. This article elaborates on various hydrogel-based delivery vectors, examining their efficacy in the local treatment of brain tumors. Additionally, it reviews the fundamental principles involved in designing intelligent hydrogels that can circumvent the BBB and penetrate larger tumor areas, thereby facilitating precise, controlled drug release. Hydrogel-based drug delivery systems (DDSs) are posited to offer a groundbreaking approach to addressing the challenges and limitations inherent in traditional oncological therapies, which are significantly impeded by the unique structural and pathological characteristics of brain tumors.

In situ forming an injectable hyaluronic acid hydrogel for drug delivery and synergistic tumor therapy

Stimulus-responsive injectable hydrogel has the key characteristics of in situ drug-loading ability and the controlled drug release, enabling efficient delivery and precise release of chemotherapy drugs at the tumor site, thereby being used as a local drug delivery system for sustained tumor treatment. This article designed a smart responsive injectable hydrogel loaded with anti-tumor drugs and nanoparticles to achieve efficient and specific synergistic treatment of tumors. Hyaluronic acid (HA) hydrogel obtained by cross-linking HA-SH (HS) and HA-Tyr (HT) through horseradish peroxidase (HRP), and doxorubicin hydrochloride (DOX) and folic acid-polyethylene glycol-amine (FA-PEG-NH2) modified PDA (denoted as PPF) were encapsulated to construct the HS/HT@PPF/D hydrogel. The hydrogel had good biocompatibility, injectability, and could respond to multiple stimuli at the tumor site, thereby achieving controlled drug release. At the same time, PPF gave it excellent photothermal efficiency, photothermal stability and tumor targeting. In vitro and in vivo experimental results showed that the HS/HT@PPF/D hydrogel combined with near-infrared laser irradiation could significantly improve its anti-tumor effect and could almost eliminate the entire tumor mass without obvious adverse reactions. The HS/HT@PPF/D hydrogel could achieve multi-stimulus-responsive drug delivery and be used for precise chemo-photothermal synergistic tumor treatment, thus providing a new platform for local synergistic tumor treatment.

Effects of bipolar irreversible electroporation with different pulse durations in a prostate cancer mouse model.

Irreversible electroporation (IRE) is a non-thermal ablation technique for local tumor treatment known to be influenced by pulse duration and voltage settings, affecting its efficacy. This study aims to investigate the effects of bipolar IRE with different pulse durations in a prostate cancer mouse model. The therapeutic effectiveness was assessed with in vitro cell experiments, in vivo tumor volume changes with magnetic resonance imaging, and gross and histological analysis in a mouse model. The tumor volume continuously decreased over time in all IRE-treated groups. The tumor volume changes, necroptosis (%), necrosis (%), the degree of TUNEL-positive cell expression, and ROS1-positive cell (%) in the long pulse duration-treated groups (300μs) were significantly increased compared to the short pulse duration-treated groups (100μs) (all p < 0.001). The bipolar IRE with a relatively long pulse duration at the same voltage significantly increased IRE-induced cell death in a prostate cancer mouse model.

A novel mini-retractor for retroperitoneal laparoscopic partial nephrectomy.

Retroperitoneal partial nephrectomy (RLPN) is the premier treatment for localized renal tumors despite narrow operation space. Many efforts have been taken to facilitate the operation of RLPN, but the optimal resolution remains debatable. To explore the feasibility of using Mini-lap to improve workspace and surgical vision in RLPN. A multicenter retrospective review of 51 patients who underwent RLPN with Mini-lap from January 2018 to December 2020 was conducted. Standard RLPN under three poles was performed in all cases. We highlighted the usage of Mini-lap (Teleflex Minilap percutaneous Surgical System) as a novel retractor in RLPN. Demographics, preoperative, intraoperative, and postoperative outcomes were assessed. All 51 cases completed RLPN with three ports successfully and no conversion to open surgery. The mean diameter of tumors was (3.53 ± 1.05) cm, in which 62.7% (32/51) were located anteriorly. The operation time and warm ischemic time (WIT) were (86.7 ± 15.9) min and (25.6 ± 5) min respectively. Minor complications (Clavien grade 1-2) occurred in 6 cases. The limitations were small sample size, retrospective design, and absence of control. Mini-lap could be used as a mini-retractor in RLPN, sparing extra assistant ports, expanding workspace, and optimizing vision. With highlights of larger workspace and less instrument interference, mini-lap could be applied in retroperitoneal laparoscopic partial nephrectomy.

Local Treatment of Desmoid Tumors: An Update.

Desmoid tumors (DTs) are rare fibroblastic proliferations, characterized by infiltrative growth and a propensity for local recurrence. Traditional strategies such as surgery, radiotherapy, and chemotherapy are the mainstays of treatment, each with its limitations and associated risks. The trend in DT management leans toward a "wait-and-see" strategy, emphasizing active surveillance supported by continuous MRI monitoring. This approach acknowledges the unpredictable nature of the disease, and a multidisciplinary management of DT requires a nuanced approach, integrating traditional therapies with emerging interventional techniques. This review highlights the emerging role of minimally invasive interventional radiological technologies and discusses interventional radiology techniques, including chemical, radiofrequency, microwave, cryoablation, and high-intensity focused ultrasound ablations as well as transarterial embolization.

Dynamic Treatment Strategy of Chinese Medicine for Metastatic Colorectal Cancer Based on Machine Learning Algorithm.

To establish the dynamic treatment strategy of Chinese medicine (CM) for metastatic colorectal cancer (mCRC) by machine learning algorithm, in order to provide a reference for the selection of CM treatment strategies for mCRC. From the outpatient cases of mCRC in the Department of Oncology at Xiyuan Hospital, China Academy of Chinese Medical Sciences, 197 cases that met the inclusion criteria were screened. According to different CM intervention strategies, the patients were divided into 3 groups: CM treatment alone, equal emphasis on Chinese and Western medicine treatment (CM combined with local treatment of tumors, oral chemotherapy, or targeted drugs), and CM assisted Western medicine treatment (CM combined with intravenous regimen of Western medicine). The survival time of patients undergoing CM intervention was taken as the final evaluation index. Factors affecting the choice of CM intervention scheme were screened as decision variables. The dynamic CM intervention and treatment strategy for mCRC was explored based on the cost-sensitive classification learning algorithm for survival (CSCLSurv). Patients' survival was estimated using the Kaplan-Meier method, and the survival time of patients who received the model-recommended treatment plan were compared with those who received actual treatment plan. Using the survival time of patients undergoing CM intervention as the evaluation index, a dynamic CM intervention therapy strategy for mCRC was established based on CSCLSurv. Different CM intervention strategies for mCRC can be selected according to dynamic decision variables, such as gender, age, Eastern Cooperative Oncology Group score, tumor site, metastatic site, genotyping, and the stage of Western medicine treatment at the patient's first visit. The median survival time of patients who received the model-recommended treatment plan was 35 months, while those who receive the actual treatment plan was 26.0 months (P=0.06). The dynamic treatment strategy of CM, based on CSCLSurv for mCRC, plays a certain role in providing clinical hints in CM. It can be further improved in future prospective studies with larger sample sizes.

Incidence, therapy, and prognosis of prostate cancer in Baden-Württemberg: analysis based on cancer registry data

Prostate cancer (PCa) is the most common solid tumor in men in Germany. Collection of epidemiological and clinical data has been centralized for several years due to legal requirements via the state cancer registries. Thus, the reporting of diagnosis, therapy, and progression of cancer is obligatory in Germany. These data needs to be processed based on the questions of the treating physicians. Intention of this work was to present the development of new cases, disease stages, treatment procedures and prognosis of PCa in Baden-Württemberg (BW). For this purpose, data of the cancer registry BW regarding patients with PCa first diagnosed between 2013 and 2021 were evaluated. The evaluation was performed using descriptive statistics, Χ2 test and Kaplan-Meier analysis. A total of 84,347 new diagnoses of PCa were reported. Clinical stage was present in 55.3% of patients. Assignment by International Society of Urological Pathology (ISUP) groups was present in 75.7%. Asteady increase in primary diagnosis was evident through 2019. The proportion of primary metastatic disease decreased (2013: 19.6% vs. 2021: 12.0%), and the proportion of localized tumors increased (2013: 65.5% vs. 2021: 77.1%). Radical prostatectomy (RP) dominated the treatment of localized tumors with amean of 60.1%. The proportion of robot-assisted surgery increased from 23.7% (2013) to 60.8% (2021) with adecrease in the R1 rate from 34.8 to 26.2%. Progression-free survival correlated closely with tumor stage and ISUP group. An increase in PCa cases and adecrease of advanced tumors were observed. Treatment was mostly surgical in localized stages, with increasing proportion of robotic-assisted RP. Early diagnosis and treatment are critical for long-term prognosis.

Preclinical Application of CEST MRI to Detect Early and Regional Tumor Response to Local Brain Tumor Treatment.

Treating glioblastoma and monitoring treatment response non-invasively remain challenging. Here, we developed a robust approach using a drug-loaded liposomal hydrogel that is mechanically compatible with the brain, and, simultaneously, we successfully monitored early tumor response using Chemical Exchange Saturation Transfer (CEST) MRI. This CEST-detectable liposomal hydrogel was optimized based on a sustainable drug release and a soft hydrogel for the brain tumor, which is unfavorable for tumor cell proliferation. After injecting the hydrogel next to the tumor, three distinctive CEST contrasts enabled the monitoring of tumor response and drug release longitudinally at 3T. As a result, a continuous tumor volume decrease was observed in the treatment group along with a significant decrease in CEST contrasts relating to the tumor response at 3.5 ppm (Amide Proton Transfer; APT) and at -3.5 ppm (relayed Nuclear Overhauser Effect; rNOE) when compared to the control group (p < 0.05). Interestingly, the molecular change at 3.5 ppm on day 3 (p < 0.05) was found to be prior to the significant decrease in tumor volume on day 5. An APT signal also showed a strong correlation with the number of proliferating cells in the tumors. This demonstrated that APT detected a distinctive decrease in mobile proteins and peptides in tumors before the change in tumor morphology. Moreover, the APT signal showed a regional response to the treatment, associated with proliferating and apoptotic cells, which allowed an in-depth evaluation and prediction of the tumor treatment response. This newly developed liposomal hydrogel allows image-guided brain tumor treatment to address clinical needs using CEST MRI.

Outcomes in dogs undergoing surgical stabilization and non-stereotactic radiation therapy for axial and appendicular bone tumors.

Information on dogs that undergo radiation therapy (RT) with non-stereotactic protocols in addition to surgical stabilization with implant placement for treatment of bone tumors is limited. Our primary objectives were to describe the clinical characteristics as well as short- and long-term outcomes, including complications, function, and disease progression, in dogs that underwent both surgical stabilization with implant placement and non-stereotactic RT for local treatment of a bone tumor. A bi-institutional retrospective case series was performed. Eight client-owned dogs that underwent both surgical stabilization with implant placement and non-stereotactic RT for local treatment of a bone tumor were included. Tumor types included osteosarcoma or suspected osteosarcoma (5), plasma cell tumor (2), and grade 3 fibrosarcoma (1). Radiation protocols were hypofractionated (palliative intent) in 5 dogs and fractionated (definitive intent) in 3 dogs. Five dogs experienced complications following both RT and surgery, including grade 1 complications in two dogs, a grade 2 complication in one dog, both grade 1 and 2 complications in one dog, and both grade 2 and 3 complications in one dog. Clinical signs subjectively improved in all dogs that had outcomes relative to function documented post-surgery/RT (7). Of these 7 dogs, 4 maintained long-term improvement in function and clinical signs, whereas 3 experienced subsequent recurrence/progression of clinical signs at a median of 133 days (range 91-186) postoperatively in association with biomechanical complications (screw loosening), surgical site infection, and local disease progression in 1 dog each; subsequent treatment resulted in improved clinical signs for each of these 3 dogs, such that overall good long-term functional outcomes were experienced. No dogs required amputation or additional vertebral surgery as salvage for local disease control or palliation. The median progression free interval was 206 days (range 25-1078), and the median survival time was 253 days (range 122-1078) with 1 additional dog lost to follow-up at 575 days. Two dogs experienced local disease progression, and 6 dogs experienced systemic disease progression; both dogs that developed local disease progression received palliative intent RT protocols. In this cohort, dogs with primary bone tumors that underwent surgical stabilization with implant placement and hypofractionated or fractionated non-stereotactic RT for local treatment had a low incidence of major complications, good limb function and ambulation post-treatment, and relatively prolonged survival times despite disease progression.