Histogram analysis of MR quantitative parameters: are they correlated with prognostic factors in prostate cancer?

PURPOSE: To investigate the correlation between quantitative MR parameters and prognostic factors in prostate cancer (PCa). METHOD: A total of 186 patients with pathologically confirmed PCa who underwent preoperative multiparametric MRI (mpMRI), including synthetic MRI (SyMRI), were enrolled from two medical centers. The histogram metrics of SyMRI [T1, T2, proton density (PD)] and apparent diffusion coefficient (ADC) values were extracted. The Mann‒Whitney U test or Student's t test was employed to determine the association between these histogram features and the prognostically relevant factors. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the differentiation performance. Spearman's rank correlation coefficients were calculated to determine the correlations between histogram parameters and the International Society of Urological Pathology (ISUP) grade group as well as pathological T stage. RESULTS: Significant correlations were found between the histogram parameters and the ISUP grade as well as pathological T stage of PCa. Among these histogram parameters, ADC_minimum had the strongest correlation with the ISUP grade (r = - 0.481, p < 0.001), and ADC_Median showed the strongest association with pathological T stage (r = - 0.285, p = 0.008). The ADC_10th percentile exhibited the highest performance in identifying clinically significant prostate cancer (csPCa) (AUC 0.833; 95% CI 0.771-0.883). When discriminating between the status of different prognostically relevant factors, a significant difference was observed between extraprostatic extension-positive and -negative cancers with regard to histogram parameters of the ADC map (10th percentile, 90th percentile, mean, median, minimum) and T1 map (minimum) (p = 0.002-0.032). Moreover, histogram parameters of the ADC map (90th percentile, maximum, mean, median), T2 map (10th percentile, median), and PD map (10th percentile, median) were significantly lower in PCa with perineural invasion (p = 0.009-0.049). The T2 values were significantly lower in patients with seminal vesicle invasion (minimum, p = 0.036) and positive surgical margin (10th percentile, 90th percentile, mean, median, and minimum, p = 0.015-0.025). CONCLUSION: Quantitative histogram parameters derived from synthetic MRI and ADC maps may have great potential for predicting the prognostic features of PCa.

N6-methyladenosine-modified circPLPP4 sustains cisplatin resistance in ovarian cancer cells via PIK3R1 upregulation.

BACKGROUND: Cisplatin (CDDP) is the first-line chemotherapeutic strategy to treat patients with ovarian cancer (OC). The development of CDDP resistance remains an unsurmountable obstacle in OC treatment and frequently induces tumor recurrence. Circular RNAs (circRNAs) are noncoding RNAs with important functions in cancer progression. Whether circRNAs function in CDDP resistance of OC is unclear. METHODS: Platinum-resistant circRNAs were screened via circRNA deep sequencing and examined using in situ hybridization (ISH) in OC. The role of circPLPP4 in CDDP resistance was assessed by clone formation and Annexin V assays in vitro, and by OC patient-derived xenografts and intraperitoneal tumor models in vivo. The mechanism underlying circPLPP4-mediated activation of miR-136/PIK3R1 signaling was examined by luciferase reporter assay, RNA pull-down, RIP, MeRIP and ISH. RESULTS: circPLPP4 was remarkably upregulated in platinum resistant OC. circPLPP4 overexpression significantly enhanced, whereas circPLPP4 silencing reduced, OC cell chemoresistance. Mechanistically, circPLPP4 acts as a microRNA sponge to sequester miR-136, thus competitively upregulating PIK3R1 expression and conferring CDDP resistance. The increased circPLPP4 level in CDDP-resistant cells was caused by increased RNA stability, mediated by increased N6-methyladenosine (m6A) modification of circPLPP4. In vivo delivery of an antisense oligonucleotide targeting circPLPP4 significantly enhanced CDDP efficacy in a tumor model. CONCLUSIONS: Our study reveals a plausible mechanism by which the m6A -induced circPLPP4/ miR-136/ PIK3R1 axis mediated CDDP resistance in OC, suggesting that circPLPP4 may serve as a promising therapeutic target against CDDP resistant OC. A circPLPP4-targeted drug in combination with CDDP might represent a rational regimen in OC.

Phase I study of the Syk inhibitor sovleplenib in relapsed or refractory mature B-cell tumors.

Sovleplenib (HMPL-523) is a selective spleen tyrosine kinase (Syk) inhibitor with antitumor activity in preclinical models of B-cell malignancy. We conducted a dose-escalation and dose-expansion phase I study of sovleplenib in patients with relapsed/refractory mature Bcell tumors. Dose escalation followed a 3+3 design; patients received oral sovleplenib (200-800 mg once daily [q.d.] or 200 mg twice daily [b.i.d.], 28-day cycles). During dose expansion, patients were enrolled into four cohorts per lymphoma classification and treated at the recommended phase 2 dose (RP2D). Overall, 134 Chinese patients were enrolled (dose escalation, n=27; dose expansion, n=107). Five patients experienced dose-limiting toxicities: one each of amylase increased (200 mg q.d.), febrile neutropenia (800 mg q.d), renal failure (800 mg q.d.), hyperuricemia and blood creatine phosphokinase increased (200 mg b.i.d.) and blood bilirubin increased and pneumonia (200 mg b.i.d.). RP2D was determined as 600 mg (>65 kg) or 400 mg (≤65 kg) q.d. The primary efficacy end point of independent review committee-assessed objective response rate in indolent B-cell lymphoma was 50.8% (95% CI, 37.5-64.1) in 59 evaluable patients at RP2D (follicular lymphoma: 60.5%, marginal zone lymphoma: 28.6%, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, 0%). The most common (≥10% patients) grade ≥3 treatment-related adverse events in the doseexpansion phase were decreased neutrophil count (29.9%), pneumonia (12.1%) and decreased white blood cell count (11.2%). Pharmacokinetic exposures increased doseproportionally with ascending dose levels from 200-800 mg, without observed saturation. Sovleplenib showed antitumor activity in relapsed/refractory B-cell lymphoma with acceptable safety. Further studies are warranted.

Assessment of Prophylactic Internal Carotid Artery Management in Postradiation Nasopharyngeal Necrosis Patients.

OBJECTIVE: Postradiation nasopharyngeal necrosis (PRNN) frequently develops after second-course radiotherapy for nasopharyngeal carcinoma (NPC). PRNN can lead to internal carotid artery (ICA) massive hemorrhage due to ICA rupture, resulting in sudden death. This study aims to explore the pretreatment of the ICA to prevent fatal massive hemorrhage in PRNN patients. STUDY DESIGN: Retrospective cohort study. SETTING: Sun Yat-sen University Cancer Center. METHODS: Patients diagnosed with NPC and PRNN from January 2010 to September 2022 were included. The Cox proportional hazards regression analysis was performed to analyze risk factors for massive hemorrhage and survival. A nomogram was developed to integrate prognostic models and perform parameter calibration. RESULTS: Two hundred and fifty-four PRNN patients were included in this study. Prophylactic ICA occlusion significantly reduced the risk of ICA hemorrhage compared to no prophylactic ICA occlusion (3.6% vs 40.6%, P < .001). Surgical repair on necrosis significantly prevented hemorrhage and improved survival. The nomogram, incorporating the above 2 factors and the nearest distance from necrosis to ICA ≤ 3 mm, exhibited excellent discriminative ability for hemorrhage. We identified 3 high-risk factors that indicate the need for prophylactic ICA management in PRNN patients: (1) exposure of ICA by rhinoscopy; (2) signs of ICA erosion on MRA scanning; (3) the depth of soft tissue coverage surrounding the ICA wall within the necrotic cavity is less than 3 mm on magnetic resonance imaging. CONCLUSION: We have identified 3 high-risk factors for PRNN patients that necessitate prophylactic ICA management. These findings are expected to contribute to improving the quality of life and overall survival of PRNN patients.

Radiomics Prediction of Muscle Invasion in Bladder Cancer Using Semi-Automatic Lesion Segmentation of MRI Compared with Manual Segmentation.

Conventional radiomics analysis requires the manual segmentation of lesions, which is time-consuming and subjective. This study aimed to assess the feasibility of predicting muscle invasion in bladder cancer (BCa) with radiomics using a semi-automatic lesion segmentation method on T2-weighted images. Cases of non-muscle-invasive BCa (NMIBC) and muscle-invasive BCa (MIBC) were pathologically identified in a training cohort and in internal and external validation cohorts. For bladder tumor segmentation, a deep learning-based semi-automatic model was constructed, while manual segmentation was performed by a radiologist. Semi-automatic and manual segmentation results were respectively used in radiomics analyses to distinguish NMIBC from MIBC. An equivalence test was used to compare the models' performance. The mean Dice similarity coefficients of the semi-automatic segmentation method were 0.836 and 0.801 in the internal and external validation cohorts, respectively. The area under the receiver operating characteristic curve (AUC) were 1.00 (0.991) and 0.892 (0.894) for the semi-automated model (manual) on the internal and external validation cohort, respectively (both p < 0.05). The average total processing time for semi-automatic segmentation was significantly shorter than that for manual segmentation (35 s vs. 92 s, p < 0.001). The BCa radiomics model based on semi-automatic segmentation method had a similar diagnostic performance as that of manual segmentation, while being less time-consuming and requiring fewer manual interventions.

Efficacy of sequential chemoradiotherapy combined with toripalimab in de novo metastatic nasopharyngeal carcinoma: A phase II trial.

Locoregional radiotherapy added to chemotherapy has significantly improved survival in de novo metastatic nasopharyngeal carcinoma (mNPC). However, only 54% of de novo mNPC patients who received sequential chemoradiotherapy have complete or partial response 3 months after radiotherapy. This Simon's optimal two-stage design phase II study (NCT04398056) investigates whether PD-1 inhibitor could improve tumor control in combination with chemoradiation. The primary endpoint is objective response rate (ORR) at 3 months after radiotherapy. Twenty-two patients with primary mNPC are enrolled. The ORR at 3 months after radiotherapy is 81.8% (22.7% complete response, n = 5; 59.1% partial response, n = 13), and the disease control rate is 81.8%. The 3-year progression-free survival (PFS) rate is 44.9% (95% confidence interval 26.4%-76.3%). Fifteen patients (68.2%) experienced grade 3-4 adverse events. Patients with high baseline plasma Epstein-Barr virus DNA copy number (>104 cps/mL) show worse PFS. Addition of toripalimab to sequential chemoradiotherapy suggests promising tumor response in patients with primary mNPC.

A Rulefit-based prognostic analysis using structured MRI report to select potential beneficiaries from induction chemotherapy in advanced nasopharyngeal carcinoma: A dual-centre study.

BACKGROUND AND PURPOSE: Structured MRI report facilitate prognostic prediction for nasopharyngeal carcinoma (NPC). However, the intrinsic association among structured variables is not fully utilised. This study aimed to investigate the performance of a Rulefit-based model in feature integration behind structured MRI report and prognostic prediction in advanced NPC. MATERIALS AND METHODS: We retrospectively enrolled 1207 patients diagnosed with non-metastatic advanced NPC from two centres, and divided into training (N = 544), internal testing (N = 367), and external testing (N = 296) cohorts. Machine learning algorithms including multivariate analysis, deep learning, Lasso, and Rulefit were used to establish corresponding prognostic models. The concordance indices (C- indices) of three clinical and six combined models with different algorithms for overall survival (OS) prediction were compared. Survival benefits of induction chemotherapy (IC) were calculated among risk groups stratified by different models. A website was established for individualised survival visualisation. RESULTS: Incorporating structured variables into Stage model significantly improved the prognostic prediction performance. Six prognostic rules with structured variables were identified by Rulefit. OS prediction of Rules model was comparable to Lasso model in internal testing cohort (C-index: 0.720 vs. 0.713, P = 0.100) and achieved the highest C-index of 0.711 in external testing cohort, indicating better generalisability. The Rules model stratified patients into risk groups with significant 5-year OS differences in each cohort, and revealed significant survival benefits from additional IC in high-risk group. CONCLUSION: The Rulefit-based Rules model, with the revelation of intrinsic associations behind structured variables, is promising in risk stratification and guiding individualised IC treatment for advanced NPC.

Deep Semi-Supervised Ultrasound Image Segmentation by Using a Shadow Aware Network With Boundary Refinement.

Accurate ultrasound (US) image segmentation is crucial for the screening and diagnosis of diseases. However, it faces two significant challenges: 1) pixel-level annotation is a time-consuming and laborious process; 2) the presence of shadow artifacts leads to missing anatomy and ambiguous boundaries, which negatively impact reliable segmentation results. To address these challenges, we propose a novel semi-supervised shadow aware network with boundary refinement (SABR-Net). Specifically, we add shadow imitation regions to the original US, and design shadow-masked transformer blocks to perceive missing anatomy of shadow regions. Shadow-masked transformer block contains an adaptive shadow attention mechanism that introduces an adaptive mask, which is updated automatically to promote the network training. Additionally, we utilize unlabeled US images to train a missing structure inpainting path with shadow-masked transformer, which further facilitates semi-supervised segmentation. Experiments on two public US datasets demonstrate the superior performance of the SABR-Net over other state-of-the-art semi-supervised segmentation methods. In addition, experiments on a private breast US dataset prove that our method has a good generalization to clinical small-scale US datasets.

First-line induction chemotherapy with high-dose methotrexate versus teniposide in patients with newly diagnosed primary central nervous system lymphoma: a retrospective, multicenter cohort study.

BACKGROUND: This study aimed to compare the efficacy and safety of high-dose methotrexate (HD-MTX) versus teniposide (TEN) in patients with newly diagnosed immunocompetent primary central nervous system lymphomas (PCNSLs). METHODS: The study included immunocompetent, adult patients with newly diagnosed PCNSL at 22 centers in China from 2007 to 2016. The patients received HD-MTX or TEN as first-line induction therapy. The objective response rate, progression-free survival, and overall survival were analyzed for each patient cohort. RESULTS: A total of 96 patients were eligible: 62 received HD-MTX, while 34 received teniposide. The overall response rate was 73.2% and 72.7% in the MTX and the TEN cohorts, respectively (P = 0.627). The median progression-free survival was 28.4 months [95% confidence interval (CI): 13.7-51.2] in the MTX cohort and 24.3 months (95% CI: 16.6-32.1) in the TEN cohort (P = 0.75). The median overall survival was 31 months (95% CI: 26.8-35.2) in the MTX cohort and 32 months (95% CI: 27.6-36.4) in the TEN cohort (P = 0.77). The incidence of any grade of coagulopathy/deep-vein thrombosis and gastrointestinal disorders was significantly higher in the MTX cohort than in the TEN cohort; no significant difference was found in the incidence of other adverse events between the two cohorts. CONCLUSIONS: This was the first multicenter study using TEN as the main agent compared with HD-MTX in newly diagnosed primary CNS lymphoma. The TEN-based regimen was non-inferior to the HD-MTX-based regimen with similar overall responses. CLASSIFICATION OF EVIDENCE: This study provided Class III evidence that the teniposide-based regimen was non-inferior to high-dose methotrexate - based regimen with similar overall responses and long-time survival in immunocompetent patients with PCNSL.

Partial preservation of the normal thyroid gland based on tumor diameter may be possible in small medullary thyroid carcinoma: a two-center 15-year retrospective study.

Background: At present, there are some controversies in the formulation of surgical protocol for small medullary thyroid carcinoma(s-MTC). We wanted to explore the feasibility of normal thyroid gland retention in small medullary thyroid carcinoma based on different tumor diameters and its prognostic impact on the tumor. Methods: The data of patients with stage T1 MTC treated at Tianjin Cancer Hospital and Sichuan Cancer Hospital from 2006 to 2021 were analyzed. The tumor diameters of 0.5 cm and 1.0 cm were used as dividing points. The outcomes were tumor recurrence, metastasis, or patient death. Survival was estimated by the Kapan-Meier curve. Results: A total of 121 T1 s-MTC patients were included, including 55 with total thyroidectomy (TT) and 66 with subthyroidectomy (Sub-TT). There were eleven cases of tumor recurrence and metastasis, and four patients died. When the tumor diameter was 1.0 cm as the cut-off point, tumor diameter (p = 0.010), TT (p = 0.028), unilateral and bilateral type (p = 0.009), and TNM staging (p = 0.007) had significant effects on progression-free survival (PFS). The tumor diameter, unilateral and bilateral type, and TT were risk factors for the prognosis of T1 MTC (p < 0.05). Conclusion: The tumor diameter of 1.0 cm can be used as a cut-off point for stage T1 MTC. Alt-hough there was no significant difference in overall survival (OS) between T1a and T1b in patients, tumor diameter significantly influenced PFS. TT is not necessary for patients with sporadic MTC with T1a.

Camrelizumab plus famitinib in patients with recurrent or metastatic nasopharyngeal carcinoma treated with PD-1 blockade: data from a multicohort phase 2 study.

Background: Treatment options for patients with recurrent/metastatic nasopharyngeal carcinoma (RM-NPC) are not clear after progression on previous treatment with PD-(L)1 inhibitor; critical gaps in evidence remain for such cases. Immunotherapy combined with antiangiogenic therapy has been reported to have synergistic antitumor activity. Therefore, we evaluated the efficacy and safety of camrelizumab plus famitinib in patients with RM-NPC who failed treatment with PD-1 inhibitor-containing regimens. Methods: This multicenter, adaptive Simon minimax two-stage, phase II study enrolled patients with RM-NPC refractory to at least one line of systemic platinum-containing chemotherapy and anti-PD-(L)1 immunotherapy. The patient received camrelizumab 200 mg every 3 weeks and famitinib 20 mg once per day. The primary endpoint was objective response rate (ORR), and the study could be stopped early as criterion for efficacy was met (>5 responses). Key secondary endpoints included time to response (TTR), disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety. This trial was registered with ClinicalTrials.gov, NCT04346381. Findings: Between October 12, 2020, and December 6, 2021, a total of 18 patients were enrolled since six responses were observed. The ORR was 33.3% (90% CI, 15.6-55.4) and the DCR was 77.8% (90% CI, 56.1-92.0). The median TTR was 2.1 months, the median DoR was 4.2 months (90% CI, 3.0-not reach), and the median PFS was 7.2 months (90% CI, 4.4-13.3), with a median follow-up duration of 16.7 months. Treatment-related adverse events (TRAEs) of grade ≥3 were reported in eight (44.4%) patients, with the most common being decreased platelet count and/or neutropenia (n = 4, 22.2%). Treatment-related serious AEs occurred in six (33.3%) patients, and no deaths occurred due to TRAEs. Four patients developed grade ≥3 nasopharyngeal necrosis; two of them developed grade 3-4 major epistaxis, and they were cured by nasal packing and vascular embolization. Interpretation: Camrelizumab plus famitinib exhibited encouraging efficacy and tolerable safety profiles in patients with RM-NPC who failed frontline immunotherapy. Further studies are needed to confirm and expand these findings. Funding: Jiangsu Hengrui Pharmaceutical Co., Ltd.

Expert consensus on microtransplant for acute myeloid leukemia in elderly patients -report from the international microtransplant interest group.

Recent studies have shown that microtransplant (MST) could improve outcome of patients with elderly acute myeloid leukemia (EAML). To further standardize the MST therapy and improve outcomes in EAML patients, based on analysis of the literature on MST, especially MST with EAML from January 1st, 2011 to November 30th, 2022, the International Microtransplant Interest Group provides recommendations and considerations for MST in the treatment of EAML. Four major issues related to MST for treating EAML were addressed: therapeutic principle of MST (1), candidates for MST (2), induction chemotherapy regimens (3), and post-remission therapy based on MST (4). Others included donor screening, infusion of donor cells, laboratory examinations, and complications of treatment.

MSU-Net: Multi-scale Sensitive U-Net based on pixel-edge-region level collaborative loss for nasopharyngeal MRI segmentation.

Radiotherapy is the traditional treatment of early nasopharyngeal carcinoma (NPC). Automatic accurate segmentation of risky lesions in the nasopharynx is crucial in radiotherapy. U-Net has been proved its effective medical image segmentation ability. However, the great difference in the structure and size of nasopharynx among different patients requires a network that pays more attention to multi-scale information. In this paper, we propose a multi-scale sensitive U-Net (MSU-Net) based on pixel-edge-region level collaborative loss (LCo-PER) for NPC segmentation task. A series of novel feature fusion modules based on spatial continuity and multi-scale semantic are proposed for extracting multi-level features while efficiently searching for all size lesions. A spatial continuity information extraction module (SCIEM) is proposed for effectively using the spatial continuity information of context slices to search small lesions. And a multi-scale semantic feature extraction module (MSFEM) is proposed for extracting features of different receptive fields. LCo-PER is proposed for the network training which makes network model could take into account the size of different lesions. The global Dice, Precision, Recall and IOU of the testing set are 84.50%, 97.48%, 84.33% and 82.41%, respectively. The results show that our method is better than the other state-of-the-art methods for NPC segmentation which obtain higher accuracy and effective segmentation performance.

Predicting muscle invasion in bladder cancer based on MRI: A comparison of radiomics, and single-task and multi-task deep learning.

BACKGROUND AND OBJECTIVES: Radiomics and deep learning are two popular technologies used to develop computer-aided detection and diagnosis schemes for analysing medical images. This study aimed to compare the effectiveness of radiomics, single-task deep learning (DL) and multi-task DL methods in predicting muscle-invasive bladder cancer (MIBC) status based on T2-weighted imaging (T2WI). METHODS: A total of 121 tumours (93 for training, from Centre 1; 28 for testing, from Centre 2) were included. MIBC was confirmed with pathological examination. A radiomics model, a single-task model, and a multi-task model based on T2WI were constructed in the training cohort with five-fold cross-validation, and validation was conducted in the external test cohort. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of each model. DeLong's test and a permutation test were used to compare the performance of the models. RESULTS: The area under the ROC curve (AUC) values of the radiomics, single-task and multi-task models in the training cohort were: 0.920, 0.933 and 0.932, respectively; and were 0.844, 0.884 and 0.932, respectively, in the test cohort. The multi-task model achieved better performance in the test cohort than did the other models. No statistically significant differences in AUC values and Kappa coefficients were observed between pairwise models, in either the training or test cohorts. According to the Grad-CAM feature visualization results, the multi-task model focused more on the diseased tissue area in some samples of the test cohort compared with the single-task model. CONCLUSIONS: The T2WI-based radiomics, single-task, and multi-task models all exhibited good diagnostic performance in preoperatively predicting MIBC, in which the multi-task model had the best diagnostic performance. Compared with the radiomics method, our multi-task DL method had the advantage of saving time and effort. Compared with the single-task DL method, our multi-task DL method had the advantage of being more lesion-focused and more reliable for clinical reference.

Camrelizumab Plus Apatinib in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma: An Open-Label, Single-Arm, Phase II Study.

PURPOSE: Immune checkpoint inhibitors combined with antiangiogenic therapy reportedly have potential synergistic antitumor activity. We investigated the activity and safety of this regimen for recurrent/metastatic nasopharyngeal carcinoma (NPC). METHODS: This single-arm, Simon two-stage study enrolled patients with recurrent/metastatic NPC who were refractory to at least first-line systemic therapy and treatment-naive to immune checkpoint inhibitors. The patients received camrelizumab 200 mg once every 3 weeks and apatinib 250 mg once per day. The primary end point was the objective response rate. Key secondary end points included disease control rate, progression-free survival, duration of response, overall survival, and safety. RESULTS: Between October 14, 2020, and December 23, 2021, 58 patients were enrolled, and all were included in the efficacy and safety analysis set. The objective response rate was 65.5% (95% CI, 51.9 to 77.5), and the disease control rate was 86.2% (95% CI, 74.6 to 93.9). The median duration of response was not reached, and the median progression-free survival was 10.4 months (95% CI, 7.2 to 13.6), with a median follow-up duration of 12.4 months (range, 2.1-19.9 months). Treatment-related adverse events (TRAEs) of grade 3 or higher were reported in 34 (58.6%) patients, with the most common being hypertension (19.0%), nasopharyngeal necrosis (15.5%), headache (12.1%), AST elevation (10.3%), and creatine phosphokinase elevation (10.3%). Sixteen (27.6%) patients discontinued apatinib treatment before progression because of unbearable TRAEs, and the most common complication was nasopharyngeal necrosis (9/16; 56.3%). Recurrent nasopharyngeal lesions (odds ratio, 5.94 [95% CI, 1.45 to 24.24]) and reirradiation (odds ratio, 5.33 [95% CI, 1.15 to 24.79]) were significantly positively correlated with nasopharyngeal necrosis. CONCLUSION: Camrelizumab plus apatinib had promising antitumor activity in patients with refractory recurrent/metastatic NPC who failed first-line therapy. Moderate to severe TRAEs were experienced by 58.6%, including nasopharyngeal necrosis associated with local recurrence and a history of reirradiation.

Predicting muscle invasion in bladder cancer by deep learning analysis of MRI: comparison with vesical imaging-reporting and data system.

OBJECTIVES: To compare the diagnostic performance of a novel deep learning (DL) method based on T2-weighted imaging with the vesical imaging-reporting and data system (VI-RADS) in predicting muscle invasion in bladder cancer (MIBC). METHODS: A total of 215 tumours (129 for training and 31 for internal validation, centre 1; 55 for external validation, centre 2) were included. MIBC was confirmed by pathological examination. VI-RADS scores were provided by two groups of radiologists (readers 1 and readers 2) independently. A deep convolutional neural network was constructed in the training set, and validation was conducted on the internal and external validation sets. ROC analysis was performed to evaluate the performance for MIBC diagnosis. RESULTS: The AUCs of the DL model, readers 1, and readers 2 were as follows: in the internal validation set, 0.963, 0.843, and 0.852, respectively; in the external validation set, 0.861, 0.808, and 0.876, respectively. The accuracy of the DL model in the tumours scored VI-RADS 2 or 3 was higher than that of radiologists in the external validation set: for readers 1, 0.886 vs. 0.600, p = 0.006; for readers 2, 0.879 vs. 0.636, p = 0.021. The average processing time (38 s and 43 s in two validation sets) of the DL method was much shorter than the readers, with a reduction of over 100 s in both validation sets. CONCLUSIONS: Compared to radiologists using VI-RADS, the DL method had a better diagnostic performance, shorter processing time, and robust generalisability, indicating good potential for diagnosing MIBC. KEY POINTS: • The DL model shows robust performance for MIBC diagnosis in both internal and external validation. • The diagnostic performance of the DL model in the tumours scored VI-RADS 2 or 3 is better than that obtained by radiologists using VI-RADS. • The DL method shows potential in the preoperative assessment of MIBC.

Application of synthetic magnetic resonance imaging and DWI for evaluation of prognostic factors in cervical carcinoma: a prospective preliminary study.

OBJECTIVES: To determine the values of quantitative metrics derived from synthetic MRI (SyMRI) and apparent diffusion coefficient (ADC) in evaluating the prognostic factors of cervical carcinoma (CC). METHODS: In this prospective study, 74 patients with pathologically confirmed CC were enrolled. Pretreatment quantitative metrics including T1, T2 and ADC values were obtained from SyMRI and diffusion-weighted imaging (DWI) sequences. The values of all metrics were compared for different prognostic features using Student's t-test or Mann-Whitney U-test. The receiver operating characteristic (ROC) curve and multivariate logistic regression analysis were utilized to evaluate the diagnostic performance of quantitative variables. RESULTS: T1 and T2 values of parametrial involvement (PMI)-negative were significantly higher than those of PMI-positive (p = 0.002 and < 0.001), while ADC values did not show a significant difference. The area under curve (AUC) of T1 and T2 values for identifying PMI were 0.743 and 0.831. Only the T2 values showed a significant difference between the lymphovascular space involvement (LVSI)-negative and LVSI-positive (p < 0.001), and the AUC of T2 values for discriminating LVSI was 0.814. The differences of T1, T2, and ADC values between the well/moderately and the poorly differentiated CC were significant (all p < 0.001). The AUCs of T1, T2 and ADC values for predicting differentiation grades were 0.762, 0.830, and 0.808. The combined model of all metrics proved to achieve good diagnostic performance with the AUC of 0.866. CONCLUSION: SyMRI may be a potential noninvasive tool for assessing the prognostic factors such as PMI, LVSI, and differentiation grades in CC. Moreover, the overall diagnostic performances of synthetic quantitative metrics were superior to the ADC values, especially in identifying PMI and LVSI. ADVANCES IN KNOWLEDGE: This is the first study to assess the utility of SyMRI-derived parameters and ADC value in evaluating the prognostic factors in CC.

False-negative and false-positive outcomes of computer-aided detection on brain metastasis: Secondary analysis of a multicenter, multireader study.

BACKGROUND: Errors have seldom been evaluated in computer-aided detection on brain metastases. This study aimed to analyze false negatives (FNs) and false positives (FPs) generated by a brain metastasis detection system (BMDS) and by readers. METHODS: A deep learning-based BMDS was developed and prospectively validated in a multicenter, multireader study. Ad hoc secondary analysis was restricted to the prospective participants (148 with 1,066 brain metastases and 152 normal controls). Three trainees and 3 experienced radiologists read the MRI images without and with the BMDS. The number of FNs and FPs per patient, jackknife alternative free-response receiver operating characteristic figure of merit (FOM), and lesion features associated with FNs were analyzed for the BMDS and readers using binary logistic regression. RESULTS: The FNs, FPs, and the FOM of the stand-alone BMDS were 0.49, 0.38, and 0.97, respectively. Compared with independent reading, BMDS-assisted reading generated 79% fewer FNs (1.98 vs 0.42, P < .001); 41% more FPs (0.17 vs 0.24, P < .001) but 125% more FPs for trainees (P < .001); and higher FOM (0.87 vs 0.98, P < .001). Lesions with small size, greater number, irregular shape, lower signal intensity, and located on nonbrain surface were associated with FNs for readers. Small, irregular, and necrotic lesions were more frequently found in FNs for BMDS. The FPs mainly resulted from small blood vessels for the BMDS and the readers. CONCLUSIONS: Despite the improvement in detection performance, attention should be paid to FPs and small lesions with lower enhancement for radiologists, especially for less-experienced radiologists.

Hypomethylation and the Resultant Overexpressed PARM1: a Biomarker for Poor Prognosis of Diffuse Large B-cell Lymphoma.

Prostate androgen-regulated mucin-like protein (PARM1) is known to promote cell survival via protecting the cell surface, thus being involved in cancer development. The Gene Expression Profiling Interactive Analysis (GEPIA), MEXPRESS database, LinkedOmics database, GeneMANIA database, and the Tumor Immune Estimation Resource (TIMER) database were accessed to explore the epigenetic regulation, prognostic value, biological functions and mechanisms of PARM1 in diffuse large B-cell lymphoma (DLBCL). Hypomethylation and resultant overexpression of PARM1 was found in DLBCL. The high-level expression of PARM1 was related to the poor outcome of DLBCL patients. PARM1 participated in DNA repair, cell cycle, and cellular response to stress. PARM1 was also associated with autophagy, apoptosis, Ras pathway, and MAPK cascade. Significant kinase targets of PARM1 included ATM, CDK1, and CDK2. Significant transcription factor targets of PARM1 involved ELK1, MYC and so on. Significant miRNA targets of PARM1 included miR21, miR202, miR323, and miR345. Further analysis suggested that the PARM1 regulated autophagy through the PI3K-Akt signaling. PARM1 was found to be correlated with immune cell infiltration, which indicated the important roles of PARM1 in microenvironment of DLBCL. Our study lays a foundation for further research on the impact of PARM1 in DLBCL tumorigenesis and precision therapy.

Consensus on informed consent for participants in cancer clinical studies (2021 edition).

To fully protect the rights of participants in cancer clinical studies and clarify the key points for the ethics review of the content of informed consent forms and the process of collecting informed consent, the Medical Ethics Professional Committee of the China Anti-Cancer Association engaged in joint discussions with the ethics committees of well-known cancer hospitals in China to formulate this consensus, along with the attached general template for informed consent forms for cancer clinical studies. This work is expected to provide guidance and suggestions for the practice of the sponsors, researchers, and ethics committees.