Health-related quality of life following salvage radical prostatectomy for recurrent prostate cancer after radiotherapy or focal therapy.

BACKGROUND: Salvage radical prostatectomy (sRP) is an important treatment option for patients with recurrent prostate cancer (PCa) after radiotherapy (RT) or focal therapy (FT). However, health-related quality of life (HRQOL) after sRP depending on the primary treatment is understudied. METHODS: Patients who underwent Salvage RP for recurrent PCa were analyzed. The primary outcome of this study was HRQOL assessed by the quality-of-life questionnaire (QLQ)-C30 and its prostate specific QLQ-PR25 add-on. Secondary outcomes were functional outcome parameters (erectile function, continence) and biochemical recurrence-free survival (BRFS). Statistical analyses employed the chi-square test, Mann-Whitney U test, and Kaplan-Meier method, with a p value < 0.05 denoting significance. RESULTS: 37 patients with RT as primary treatment (RT-sRP) and 22 patients with focal therapy prior sRP (FT-sRP) were analyzed. Mean global health score was not significantly different preoperatively (71.9 vs. 67.3, p = 0.89) as well as after a median of 32 months follow-up (54.9 vs. 50.6, p = 0.63) with impaired HRQOL after sRP in both groups. Baseline erectile dysfunction was more prevalent in the RT-sRP group (mean IIEF-5: 5.0) than in the FT-sRP group (mean IIEF-5: 8.5, p = 0.037). No differences were observed at follow-up for erectile function (IIEF-5-Score: 0.5 vs 2.5, p = 0.199) and continence (continence rate: 48.4% vs 52.9% (p = 0.763) between the RT-sRP and FT-sRP group. 5-year-BRFS was 60% (RT-sRP) and 68% (FT-sRP, p = 0.849). CONCLUSIONS: sRP impacts HRQOL in patients with PCa after RT and FT with no significant differences. Comparison with HRQOL and BRFS of treatment alternatives is paramount to counsel patients for appropriate treatments.

Electro-osmotic flow in nanoconfinement: Solid-state and protein nanopores.

Electro-osmotic flow (EOF) is a phenomenon where fluid motion occurs in porous materials or micro/nano-channels when an external electric field is applied. In the particular example of single-molecule electrophoresis using single nanopores, the role of EOF on the translocation velocity of the analyte molecule through the nanopore is not fully understood. The complexity arises from a combination of effects from hydrodynamics in restricted environments, electrostatics emanating from charge decorations and geometry of the pores. We address this fundamental issue using the Poisson-Nernst-Planck and Navier-Stokes (PNP-NS) equations for cylindrical solid-state nanopores and three representative protein nanopores (α-hemolysin, MspA, and CsgG). We present the velocity profiles inside the nanopores as a function of charge decoration and geometry of the pore and applied electric field. We report several unexpected results: (a) The apparent charges of the protein nanopores are different from their net charge and the surface charge of the whole protein geometry, and the net charge of inner surface is consistent with the apparent charge. (b) The fluid velocity depends non-monotonically on voltage. The three protein nanopores exhibit unique EOF and velocity-voltage relations, which cannot be simply deduced from their net charge. Furthermore, effective point mutations can significantly change both the direction and the magnitude of EOF. The present computational analysis offers an opportunity to further understand the origins of the speed of transport of charged macromolecules in restricted space and to design desirable nanopores for tuning the speed of macromolecules through nanopores.

Planning CT Identifies Patients at Risk of High Prostate Intrafraction Motion.

Prostate motion (standard deviation, range of motion, and diffusion coefficient) was calculated from 4D ultrasound data of 1791 fractions of radiation therapy in N = 100 patients. The inner diameter of the lesser pelvis was obtained from transversal slices through the pubic symphysis in planning CTs. On the lateral and craniocaudal axes, motility increases significantly (t-test, p < 0.005) with the inner diameter of the lesser pelvis. A diameter of >106 mm (ca. 6th decile) is a good predictor for high prostate intrafraction motion (ca. 9th decile). The corresponding area under the receiver operator curve (AUROC) is 80% in the lateral direction, 68% to 80% in the craniocaudal direction, and 62% to 70% in the vertical direction. On the lateral x-axis, the proposed test is 100% sensitive and has a 100% negative predictive value for all three characteristics (standard deviation, range of motion, and diffusion coefficient). On the craniocaudal z-axis, the proposed test is 79% to 100% sensitive and reaches 95% to 100% negative predictive value. On the vertical axis, the proposed test still delivers 98% negative predictive value but is not particularly sensitive. Overall, the proposed predictor is able to help identify patients at risk of high prostate motion based on a single planning CT.

A hybrid P300-SSVEP brain-computer interface speller with a frequency enhanced row and column paradigm.

Objective: This study proposes a new hybrid brain-computer interface (BCI) system to improve spelling accuracy and speed by stimulating P300 and steady-state visually evoked potential (SSVEP) in electroencephalography (EEG) signals. Methods: A frequency enhanced row and column (FERC) paradigm is proposed to incorporate the frequency coding into the row and column (RC) paradigm so that the P300 and SSVEP signals can be evoked simultaneously. A flicker (white-black) with a specific frequency from 6.0 to 11.5 Hz with an interval of 0.5 Hz is assigned to one row or column of a 6 × 6 layout, and the row/column flashes are carried out in a pseudorandom sequence. A wavelet and support vector machine (SVM) combination is adopted for P300 detection, an ensemble task-related component analysis (TRCA) method is used for SSVEP detection, and the two detection possibilities are fused using a weight control approach. Results: The implemented BCI speller achieved an accuracy of 94.29% and an information transfer rate (ITR) of 28.64 bit/min averaged across 10 subjects during the online tests. An accuracy of 96.86% is obtained during the offline calibration tests, higher than that of only using P300 (75.29%) or SSVEP (89.13%). The SVM in P300 outperformed the previous linear discrimination classifier and its variants (61.90-72.22%), and the ensemble TRCA in SSVEP outperformed the canonical correlation analysis method (73.33%). Conclusion: The proposed hybrid FERC stimulus paradigm can improve the performance of the speller compared with the classical single stimulus paradigm. The implemented speller can achieve comparable accuracy and ITR to its state-of-the-art counterparts with advanced detection algorithms.

Metabolic patterns on [18F]FDG PET/CT in patients with unresectable stage III NSCLC undergoing chemoradiotherapy ± durvalumab maintenance treatment.

PURPOSE: In patients with unresectable stage III non-small-cell lung cancer (NSCLC), durvalumab maintenance treatment after chemoradiotherapy (CRT) significantly improves survival. So far, however, metabolic changes of tumoral lesions and secondary lymphoid organs under durvalumab are unknown. Hence, we assessed changes on [18F]FDG PET/CT in comparison to patients undergoing CRT alone. METHODS: Forty-three patients with [18F]FDG PET/CT both before and after standard CRT for unresectable stage III NSCLC were included, in 16/43 patients durvalumab maintenance treatment was initiated (CRT-IO) prior to the second PET/CT. Uptake of tumor sites and secondary lymphoid organs was compared between CRT and CRT-IO. Also, readers were blinded for durvalumab administration and reviewed scans for findings suspicious for immunotherapy-related adverse events (irAE). RESULTS: Initial uptake characteristics were comparable. However, under durvalumab, diverging metabolic patterns were noted: There was a significantly higher reduction of tumoral uptake intensity in CRT-IO compared to CRT, e.g. median decrease of SUVmax -70.0% vs. -24.8%, p = 0.009. In contrast, the spleen uptake increased in CRT-IO while it dropped in CRT (median + 12.5% vs. -4.4%, p = 0.029). Overall survival was significantly longer in CRT-IO compared to CRT with few events (progression/death) noted in CRT-IO. Findings suggestive of irAE were present on PET/CT more often in CRT-IO (12/16) compared to CRT (8/27 patients), p = 0.005. CONCLUSION: Durvalumab maintenance treatment after CRT leads to diverging tumoral metabolic changes, but also increases splenic metabolism and leads to a higher proportion of findings suggestive of irAE compared to patients without durvalumab. Due to significantly prolonged survival with durvalumab, survival analysis will be substantiated in correlation to metabolic changes as soon as more clinical events are present.

DNA-methylation and genomic copy number in primary tumors and corresponding lymph node metastases in prostate cancer from patients with low and high Gleason score.

Purpose: In prostate cancer, the indication to irradiate the pelvic lymphatic pathways in clinical node-negative patients is solely based on clinical nomograms. To define biological risk patterns of lymphatic spread, we studied DNA-methylation and genomic copy number in primary tumors and corresponding lymph nodes metastases. Methods/Patients: DNA-methylation and genomic copy number profiles of primary tumors (PT) and paired synchronous lymph node metastases (LN) from Gleason Score (GS)-6/7a (n = 20 LN-positive, n = 20 LN-negative) and GS-9/10 patients (LN-positive n = 20) after prostatectomy and lymphonodectomy were analyzed. Results: GS-6/7a pN0 PTs and GS-6/7a pN1 PTs differed in histone H3K27me3/H3K9me3 mediated methylation. PTs compared to LNs, in both, GS-6/7a pN1 and GS-9/10 pN1 patients showed large differences in DNA-methylation mediated by histones H3K4me1/2, in addition to copy number changes of chromosomal regions 11q13.1, 14q11.2 and 15q26.1. Between GS-6/7a pN1 and GS-9/10 pN1 patients, methylation levels differed more when comparing LNs than PTs. 16q21-22.1 was specifically lost in GS-9/10 pN0 PTs. Immune system-related pathways characterized the differences between PTs and LNs in both GS-6/7a pN1 and GS-9/10 pN1 patients. Comparing PTs and LKs between GS-6/7a pN1 and GS-9/10 pN1 patients revealed altered transmembrane and G-protein-coupled receptor signaling. Conclusions: Our data suggest that progression of prostate cancer, including lymphatic spread, is associated with histone-mediated DNA-methylation and we hypothesize a methylation signature predicting lymphatic spread in GS-6/7a patients from primary tumors. Lymphatic spread in GS-6/7a patients, flanked by DNA-methylation and CNA alterations, appears to be more complex than in GS-9/10 patients, in whom the primary tumors already appear to bear lymph node metastasis-enabling alterations.

Development of PSMA-PET-guided CT-based radiomic signature to predict biochemical recurrence after salvage radiotherapy.

PURPOSE: To develop a CT-based radiomic signature to predict biochemical recurrence (BCR) in prostate cancer patients after sRT guided by positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET). MATERIAL AND METHODS: Consecutive patients, who underwent 68Ga-PSMA11-PET/CT-guided sRT from three high-volume centers in Germany, were included in this retrospective multicenter study. Patients had PET-positive local recurrences and were treated with intensity-modulated sRT. Radiomic features were extracted from volumes of interests on CT guided by focal PSMA-PET uptakes. After preprocessing, clinical, radiomics, and combined clinical-radiomic models were developed combining different feature reduction techniques and Cox proportional hazard models within a nested cross validation approach. RESULTS: Among 99 patients, median interval until BCR was the radiomic models outperformed clinical models and combined clinical-radiomic models for prediction of BCR with a C-index of 0.71 compared to 0.53 and 0.63 in the test sets, respectively. In contrast to the other models, the radiomic model achieved significantly improved patient stratification in Kaplan-Meier analysis. The radiomic and clinical-radiomic model achieved a significantly better time-dependent net reclassification improvement index (0.392 and 0.762, respectively) compared to the clinical model. Decision curve analysis demonstrated a clinical net benefit for both models. Mean intensity was the most predictive radiomic feature. CONCLUSION: This is the first study to develop a PSMA-PET-guided CT-based radiomic model to predict BCR after sRT. The radiomic models outperformed clinical models and might contribute to guide personalized treatment decisions.

An Analysis of the Distribution of PSMA PET/CT-Positive Lymph Nodes and Their Coverage by Different Elective Nodal Radiation Volumes in Postoperative Prostate Cancer Patients.

Salvage elective nodal radiotherapy (ENRT) is a treatment option for patients with biochemically persistent or recurrent prostate cancer who have lymph node metastases (LNs) after prostatectomy. Possible ENRT templates were proposed by the Radiation Therapy Oncology Group (RTOG; 2009), the PIVOTAL trialists (2015), and the NRG Oncology Group (2021). The goal of this study was to analyze the distribution of prostate-specific membrane antigen (PSMA) PET/CT-positive LNs and to compare the templates regarding their LN coverage. Methods: We analyzed the PSMA PET/CT scans of 105 patients with PET-positive LNs treated with salvage ENRT from 2014 to 2019. All LNs were mapped in an exemplary dataset, classified by region, and assessed with regard to their potential coverage by the 3 ENRT templates. The primary endpoint was the number of missed LNs. The secondary endpoint was the number of patients with full coverage. To compare the templates, a t test and McNemar test were used. Results: Three hundred thirty-five LNs were contoured (3.19 per patient; 95% CI, 2.43-3.95). Most frequently, LNs were seen in the internal iliac (n = 94, 28.1%), external iliac (n = 60, 17.9%), periaortic (n = 58, 17.3%), common iliac (n = 55, 16.4%), perirectal (n = 26, 7.8%), and presacral (n = 19, 5.7%) regions. The NRG template missed fewer LNs per patient (1.01, 31.7%) than the RTOG (1.28, 40.1%, P < 0.001) and PIVOTAL templates (1.19, 37.3%, P = 0.003). No difference was observed in the number of patients with full coverage of all LNs: 52 (49.5%) with the NRG template versus 50 (47.6%) with the RTOG (P = 0.625) and 49 (46.7%) with the PIVOTAL template (P = 0.250). Conclusion: The NRG template showed better coverage than the RTOG and PIVOTAL templates. Nevertheless, in this cohort, it would have missed almost one third of all contoured LNs and would have resulted in incomplete coverage in half the patients. This result underlines the importance of advanced imaging, such as PSMA PET/CT scans, before salvage ENRT and shows the need for further individualization of ENRT fields.

A Pedestrian Detection Network Model Based on Improved YOLOv5.

Advanced object detection methods always face high algorithmic complexity or low accuracy when used in pedestrian target detection for the autonomous driving system. This paper proposes a lightweight pedestrian detection approach called the YOLOv5s-G2 network to address these issues. We apply Ghost and GhostC3 modules in the YOLOv5s-G2 network to minimize computational cost during feature extraction while keeping the network's capability of extracting features intact. The YOLOv5s-G2 network improves feature extraction accuracy by incorporating the Global Attention Mechanism (GAM) module. This application can extract relevant information for pedestrian target identification tasks and suppress irrelevant information, improving the unidentified problem of occluded and small targets by replacing the GIoU loss function used in the bounding box regression with the α-CIoU loss function. The YOLOv5s-G2 network is evaluated on the WiderPerson dataset to ensure its efficacy. Our proposed YOLOv5s-G2 network offers a 1.0% increase in detection accuracy and a 13.2% decrease in Floating Point Operations (FLOPs) compared to the existing YOLOv5s network. As a result, the YOLOv5s-G2 network is preferable for pedestrian identification as it is both more lightweight and more accurate.

Potential synergy between radiotherapy and CAR T-cells - a multicentric analysis of the role of radiotherapy in the combination of CAR T cell therapy.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy has improved the limited overall survival (OS) of patients with intensively pretreated diffuse large B-cell lymphoma (DLBCL). However, the potentially life-threatening toxicities of CAR T-cells and early relapses remain a challenge. As suggested by smaller monocentric analyses, radiotherapy (RT) in combination with CAR T-cells may have an immunomodulatory effect. METHOD/ RESULTS: In this multicentric retrospective analysis, we investigated potentially synergistic effects of RT and CAR T-cells. Of 78 patients from four centers who received CAR T-cell therapy for DLBCL, 37 patients underwent bridging RT or received salvage RT. RTs (median 36 gray) were well tolerated. Therapy response and disease control of CAR T-cell therapy were comparable after bridging RT or bridging systemic therapy. High-grade neurotoxicity tended to occur less frequently after bridging RT. After further disease progression, patients with localized relapses showed better outcomes, compared to those in advanced stage. In the subgroup with localized relapse, patients receiving salvage RT had an increased OS, vs. those without salvage RT (1-year OS rate 89% vs. 38%, p = 0.03). CONCLUSION: Our analysis demonstrated that RT in combination with CAR T-cells led neither to high-grade toxicities, nor to a decreased response rate. We observed better outcomes of salvage therapies in patients with localized relapses vs. those with advanced stage relapses. Especially the patients who received salvage RTs for localized relapses seem to benefit more. Further analyses are necessary to clarify whether specific synergistic effects exist, such as an enhanced anti-tumor effect of CAR T-cells from RT sensitizing.

Elective nodal radiotherapy with a gapless radiation field junction for oligorecurrent prostate cancer after previous radiotherapy.

Purpose: To evaluate the feasibility of subsequent elective nodal radiotherapy (ENRT) for nodal recurrences after previous radiotherapy with a defined planning approach for a gapless radiation field junction. Methods: Patients with 1) previous radiotherapy of prostate or prostatic fossa and subsequent pelvic ENRT or 2) previous pelvic radiotherapy and subsequent ENRT to paraaortic lymph nodes (LN) and gapless junction of both radiation fields were analyzed. The cumulative maximum dose (Dmax-cum) and the maximum cumulative dose in 1 cc (D1cc-cum) were estimated. Absolute toxicity and the toxicity exceeding baseline were evaluated. Results: Twenty-two patients with PSMA-PET/CT-staged nodal oligorecurrence after prior radiotherapy were treated with pelvic (14 patients) or paraaortic ENRT (9 patients). One patient was treated sequentially at both locations. Median time between first and second RT was 20.2 months. Median doses to the lymphatic pathways and to PET-positive LN were 47.5 Gy and 64.8 Gy, respectively. The planning constraint of an estimated Dmax-cum ≤ 95 Gy and of D1cc-cum < 90 Gy were achieved in 23/23 cases and 22/23 cases, respectively. Median follow-up was 33.5 months. There was no additional acute or late toxicity ≥ grade 3. Worst acute toxicity exceeding baseline was grade 1 in 68.2% and grade 2 in 22.7% of patients. Worst late toxicity exceeding baseline was grade 1 in 31.8% and grade 2 in 18.2% of patients. Conclusion: ENRT for nodal recurrences after a previous radiotherapy with gapless junction of radiation fields seems to be feasible, applying the dose constraints Dmax-cum ≤ 95 Gy and D1cc-cum < 90 Gy without grade 3 acute or late toxicities exceeding baseline.

Pharmacokinetic characteristics of emodin in polygoni Multiflori Radix Praeparata.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygoni Multiflori Radix Praeparata (Zhiheshouwu) has been a Wudang Taoist medicine for tonifying the liver and kidney, resolving turbidity and reducing lipid. Emodin is one of the active anthraquinones in Zhiheshouwu. Our previous studies showed that emodin (EM) and the other anthraquinones in Zhiheshouwu extract (HSWE) exerted similar inhibitory effects on liver cancer cells in vitro. However, it is still unknown if the other anthraquinones enhance pharmacokinetics (PK) of EM in HSWE in vivo. AIM OF THE STUDY: In this study, we compared the PK characteristics of EM alone with that in Zhiheshouwu aiming to explore which anthraquinones in HSWE contribute to the changed PK of EM in rats. MATERIALS AND METHODS: Quality control of HSWE was determined using high performance liquid chromatography (HPLC). The ratios of emodin to other anthraquinones, physcion (PH), chrysophanol (CH), rhein (RH), aloe-emodin (AE), emodin-8-O-ß-D-glycoside (EMG), physcion-1-O-ß-D-glycoside (PHG) and chrysophanol-8-O-ß-D-glycoside (CHG) in HSWE were determined and analyzed using UPLC combined with tandem mass spectrometry (UPLC/MS). The PK parameters and intestinal tissue concentration of EM alone, EM in HSWE, or with other anthraquinones in SD rats were analyzed using UPLC/MS. RESULTS: The quality of the Zhiheshouwu samples met the quality standard of the Chinese Pharmacopoeia (Version 2020). The PK results showed that compared with EM alone, Cmax (239.90 ± 146.71 vs. 898.46 ± 291.62, P < 0.001), Tmax (0.26 ± 0.15 vs. 12.55 ± 1.33, P < 0.001), AUC0-t (1575.09 ± 570.46 vs. 12154.96 ± 5394.25, P < 0.001), and AUC0-∞ (4742.51 ± 1837.62 vs. 37131.34 ± 21647.39, P < 0.001) of EM in HSWE were decreased due to PH and EMG, while the values of Vd (380.75 ± 217.74 vs. 11.75 ± 7.35, P < 0.001), T1/2 (10.81 ± 1.99 vs. 6.65 ± 2.76, P < 0.05) and CL (19.30 ± 7.82 vs. 2.78 ± 1.88, P < 0.001) of EM in HSWE were increased due to PH and AE. In addition, the intestinal tissue concentration of emodin in HSWE was decreased compared with that of EM alone in 20 and 780 min (25.37 ± 5.98 vs. 43.29 ± 4.16 and 26.72 ± 4.03 vs. 43.40 ± 14.19, respectively. P < 0.05) dominantly due to RH and PH. CONCLUSION: In conclusion, compared with treatment of EM alone, the AUC0-t value of EM in HSWE was decreased with different ways in rats. PH shortened Tmax, and increased Vd and CL. While AE prolonged T1/2 of EM. This indicated that the other anthraquinones in HSWE changed the PK of EM in rats and participated in the complex effects of EM on liver cancer. Besides the other anthraquinones, other components (e.g., 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside) in Zhiheshouwu may contribute in the pharmacokinetic and pharmacodynamic interactions with EM for anti-liver cancer.

Clinical outcomes of conventional HDR intracavitary brachytherapy combined with complementary applicator-guided intensity modulated radiotherapy boost in patients with bulky cervical tumour.

OBJECTIVE: To investigate the clinical outcomes and toxicity in patients with locally advanced cervical cancer treated with supplementary applicator guided-intensity modulated radiation therapy (IMRT) based on conventional intracavitary brachytherapy (IC/IMRT). DESIGN: A retrospective cohort study. SETTING: Sichuan Cancer Hospital & Institute, Sichuan Cancer Centre, China. POPULATION: Large high-risk clinical target volume (HR-CTV) volume (>40 ml) at the time of brachytherapy cervical cancer patients were recruited. METHODS: This study is a retrospective analysis of 76 patients with locally advanced cervical cancer (FIGO IIB-IVA) treated with concurrent chemoradiotherapy followed by IC/IMRT between June 2010 and October 2016. External radiotherapy (45 Gy in 25 fractions) was adminstered with cisplatin chemotherapy treatment before IC/IMRT. The IMRT plan was optimised using the ICBT plan base dose plan by an inverse dose optimisation tool which allows the use of DVH constraints on the total dose of ICBT. A seven-field gantry angle IMRT plan was devised to avoid hotspots when optimising the boost plan. The prescription dose for HR-CTV and IR-CTV were 6 and 5 Gy per fraction for five fractions, respectively. RESULTS: Mean HR-CTV was 65.8 ± 23.6 ml at the time of brachytherapy. D90 for HR-CTV and IR-CTV were 88.7 ± 3.6 Gy and 78.1 ± 2.5 Gy. D2cc for bladder, rectum, sigmoid and small intestine were 71.8 ± 3.8, 64.6 ± 4.9, 63.9 ± 5.3 and 56.7 ± 8.7 Gy, respectively. Median follow-up was 85 months (47.9-124.2 months). Five-year local recurrence-free survival rate, metastasis recurrence-free survival rate, disease-free survival rate and cancer-special survival rate were 87.6, 82.4, 70.9 and 76.3%, respectively. The grade 1 + 2 gastrointestinal and urinary late toxicities were 15.8 and 21.1%, and grade 3 late toxicities were 3.9 and 5.2%, respectively. Neither acute nor late grade 4 gastrointestinal or urinary toxicities were seen. CONCLUSIONS: The combination of ICBT with an applicator-guided supplementary IMRT boost achieved excellent local control and overall survival with low toxicity for bulky residual cervical tumour.

Turbulence of glutamine metabolism in pan-cancer prognosis and immune microenvironment.

Introduction: Glutamine is characterized as the nutrient required in tumor cells. The study based on glutamine metabolism aimed to develop a new predictive factor for pan-cancer prognostic and therapeutic analyses and to explore the mechanisms underlying the development of cancer. Methods: The RNA-sequence data retrieved from TCGA, ICGC, GEO, and CGGA databases were applied to train and further validate our signature. Single-cell RNA transcriptome data from GEO were used to investigate the correlation between glutamine metabolism and cell cycle progression. A series of bioinformatics and machine learning approaches were applied to accomplish the statistical analyses in this study. Results: As an individual risk factor, our signature could predict the overall survival (OS) and immunotherapy responses of patients in the pan-cancer analysis. The nomogram model combined several clinicopathological features, provided the GMscore, a readable measurement to clinically predict the probability of OS and improve the predictive capacity of GMscore. While analyzing the correlations between glutamine metabolism and malignant features of the tumor, we observed that the accumulation of TP53 inactivation might underlie glutamine metabolism with cell cycle progression in cancer. Supposedly, CAD and its upstream genes in glutamine metabolism would be potential targets in the therapy of patients with IDH-mutated glioma. Immune infiltration and sensitivity to anti-cancer drugs have been confirmed in the high-risk group. Discussion: In summary, glutamine metabolism is significant to the clinical outcomes of patients with pan-cancer and is tightly associated with several hallmarks of a malignant tumor.

Adjuvant effects of Chinese medicinal tonics on gastric, liver, and colorectal cancers-OMICs-based contributions to understanding their mechanism of action.

Gastric, liver, and colorectal cancers belong to gastrointestinal (GI) cancers, one of the most threatening diseases in the world. The tonics class in Chinese medicines plays a critical role in antigastrointestinal cancer as adjuvants. However, it is a challenge to study the effects and underlying mechanisms of tonics due to their multiple components and multiple targets; OMICs were introduced to facilitate the investigation of the complex mixture of tonics. In this review, the online databases PubMed, ProQuest, Web of Knowledge, China National Knowledge Infrastructure (CNKI), Chongqing VIP, and Wanfang were retrieved from 1 January 2011 to 31 May 2022, in an aim to summarize and discuss the research progress of the effects and, especially, the underlying mechanisms of tonics for antigastrointestinal cancers via OMICs. The results showed that through the combination of OMICs and other technologies, tonics have been used for gastrointestinal cancer by targeting cancer hallmarks, enhancing body resistance to carcinogenesis, enhancing therapeutic effects, and/or decreasing side effects. In conclusion, tonics may play a promising role in gastric, liver, and colorectal cancers as adjuvants and can be well investigated via the combination of OMICs and other technologies, which deserves further study.

Quality control, preparation process optimizing and anti-inflammatory effects of Premna Puberula Pamp. Pectin.

Background: Premna Puberula Pamp. Pectin (PP) was a Wudang functional food in China. It has the effect of dispelling fire, clearing heat and detoxification in folk medicine. However, little studies have been reported for their preparation, quality control, effects and toxicity. Methods: The P. Puberula leaves were collected from different pharms and seasons. The compounds in PP were identified using UPLC-Q-TOF-MS/MS. UV-VIS spectrophotometry with phenol-sulfuric acid and sodium nitrite aluminum nitrate were conducted for analyzing the water-soluble sugars and total flavonoids, respectively. L9(34) orthogonal experimental method was used to optimize the preparation process of PP. For the pharmacological effects of PP, the swelling right hind paw of ICR mice was modeled using subcutaneous injection of carrageenan gum solution, and the local tissue inflammatory reactions of the model mice were investigated using vernier calipers and HE staining. The serum inflammatory factor expression was detected using ELISA. The acute toxicity experiments were carried out for safety assessment of PP in ICR mice. Results: Fifty-three compounds were initially identified in PP among which flavonoids were dominant (19 out of 53). The average values of water-soluble sugar content and total flavonoid content of PP were 13.366 and 4.970 mg/g, respectively. The best preparation process of PP was powder-liquid ratio 1: 20, temperature 90 °C, and stirring time 3 min. Data showed that PP reduced paw edema and decrease the serum level of IL-6, TNF-α and IL-1ß in the model mice. There was no toxic effect of PP on mice at a total dose of 6000 mg/kg/24h. Conclusion: In summary, by optimizing the preparation process, PP with stable quality can be obtained. PP has anti-inflammatory effects without toxicity.

The Prognostic Value of Tumor Size, Volume and Tumor Volume Reduction Rate During Concurrent Chemoradiotherapy in Patients With Cervical Cancer.

Objective: This study aimed to investigate the relationship between prognostic and tumor parameters of cervical cancer patients, such as tumor size (TS), tumor volume (TV), and tumor volume reduction rate (TVRR) after external beam radiotherapy. Methods: A total of 217 patients with advanced cervical cancer, classified as Federation of Gynecology and Obstetrics (FIGO) IIa-IVa, were enrolled in the study. Pre- and mid-RT pelvic magnetic resonance imaging (MRI) were performed twice, during RT and just before brachytherapy. Results: The median follow-up time was 51 months (range, 7-111 months). The 5-year overall survival (OS), progression-free survival (PFS), and local failure-free survival (LFFS) rates were 81.3, 85.1, and 92.9%, respectively. Multivariate analysis revealed that tumor parameters including FIGO stage >II (Hazard Ratio, 2.377 and 95% confidence interval [CI], 1.091-5.182; P = 0.029), pre-RT TV >61.6 cm3 (HR, 0.417 and 95% CI, 0.188-0.926; P = 0.032), and mid-RT TV >11.38 cm3 (HR, 3.192 and 95% CI, 1.094-9.316; P = 0.034) were observably associated with OS. Univariate analysis showed that the tumor volume reduction rate (TVRR) was dramatically associated with overall survival (HR, 0.204 and 95% CI 0.033-1.282; P <0.001) and local failure-free survival (P = 0.050). Conclusions: In this retrospective study, TVRR and mid-radiotherapy tumor volume are independent and strong prognostic parameters for patients with local advanced cervical cancer receiving CCRT.

The ProMotion LMU dataset (2022 edition), prostate intra-fraction motion recorded by transperineal ultrasound.

Infra-fraction motion of the prostate was recorded during 2.385 fractions of image guided radiotherapy (IGRT) in 126 patients, 14 of which were treated by intensity modulated radiation therapy (IMRT), and 112 of which were treated by volumetric arc therapy (VMAT). The prostate was imaged by three-dimensional and time-resolved transperineal ultrasound (4D-US) of type Clarity by Elekta, Stockholm, Sweden. The prostate volume was registered and the prostate position (center of volume) was recorded at a frequency of 2.0 samples per second. This raw data set contains a total of 1.138.024 prostate and patient couch positions over a time span of 158 hours, 25 minutes and 50 seconds of life radiotherapy as exported by the instrument software. This data set has been used for the validation of models of prostate intra-fraction motion and for the estimation of the dosimetric impact of actual intra-fraction motion on treatment quality and side effects. We hope that this data set may be reused by other groups for similar purposes.

APOBEC-mediated mutagenesis is a favorable predictor of prognosis and immunotherapy for bladder cancer patients: evidence from pan-cancer analysis and multiple databases.

Background: The APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) family-mediated mutagenesis is widespread in human cancers. However, our knowledge of the biological feature and clinical relevance of APOBECs and APOBEC mutagenesis in cancers remains limited. Methods: In this study, with a series of bioinformatic and statistical approaches, we performed a comprehensive analysis of multiple levels of data, including whole-exome sequencing (WES) and targeted next-generation sequencing (NGS), transcriptome (bulk RNA-seq and single-cell RNA-seq), immune signatures and immune checkpoint blockade (ICB) potential, patient survival and drug sensitivity, to reveal the distribution characteristics and clinical significance of APOBECs and APOBEC mutagenesis in pan-cancer especially bladder cancer (BLCA). Results: APOBEC mutagenesis dominates in the mutational patterns of BLCA. A higher enrichment score of APOBEC mutagenesis correlates with favorable prognosis, immune activation and potential ICB response in BLCA patients. APOBEC3A and 3B play a significant role in the malignant progression and cell differentiation within the tumor microenvironment. Furthermore, using machine learning approaches, a prognostic APOBEC mutagenesis-related model was established and validated in different BLCA cohorts. Conclusions: Our study illustrates the characterization of APOBECs and APOBEC mutagenesis in multiple cancer types and highlights its potential value as a promising biomarker for prognosis and immunotherapy in BLCA.

Pooled analysis on image-guided moderately hypofractionated thoracic irradiation in inoperable node-positive/recurrent patients with non-small cell lung cancer with poor prognostic factors and severely limited pulmonary function and reserve.

BACKGROUND: The objective of this study was to investigate the feasibility and efficacy of image-guided moderately hypofractionated thoracic radiotherapy (hypo-IGRT) in patients with non-small cell lung cancer (NSCLC) with poor performance status and severely limited pulmonary function and reserve. METHODS: Consecutive inoperable patients who had node-positive, stage IIB-IIIC (TNM, 8th edition) or recurrent NSCLC, had an Eastern Cooperative Oncology Group performance status ≥1, and had a forced expiratory volume in 1 second (FEV1 ) ≤1.0 L, had a single-breath diffusing capacity of the lung for carbon monoxide (DLCO-SB) ≤40% and/or on long-term oxygen therapy were analyzed. All patients received hypofractionated IGRT to a total dose of 42.0 to 49.0 Gy/13 to 16 fractions (2.8-3.5 Gy/fraction) (equivalent dose in 2-Gy fractions/biologically effective dose [α/ß = 10] = 45.5-55.1 Gy/54.6-66.2 Gy) alone. Patients were monitored closely for nonhematological toxicity, which was classified per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Between 2014 and 2021, 47 consecutive patients with a median age of 72 years (range, 52.2-88 years) were treated. At baseline, the median FEV1 , vital capacity, and DLCO-SB were 1.17 L (range, 0.69-2.84 L), 2.34 L (range, 1.23-3.74 L), and 35% predicted (range, 13.3%-69.0%), respectively. The mean and median planning target volumes were 410.8 cc (SD, 267.1 cc) and 315.4 cc (range, 83.4-1174.1 cc). With a median follow-up of 28.9 months (range, 0.5-90.6 months) after RT, the median progression-free survival (PFS)/overall survival (OS) and 6- and 12-month PFS/OS rates were 10.4 months (95% CI, 7-13.8 months)/18.3 months (95% CI, 9.2-27.4 months), 70%/89.4%, and 38.8%/66%, respectively. Treatment was well tolerated with only 1 case each of grade 3 pneumonitis and esophagitis. No toxicity greater than grade 3 was observed. CONCLUSIONS: Patients with inoperable node-positive NSCLC, a poor performance status, and severely limited lung function can be safely and effectively treated with individualized moderately hypofractionated IGRT. The achieved survival rates for this highly multimorbid group of patients were encouraging.