Prediction of tumor lysis syndrome in childhood acute lymphoblastic leukemia based on machine learning models: a retrospective study.

Background: Tumor lysis syndrome (TLS) often occurs early after induction chemotherapy for acute lymphoblastic leukemia (ALL) and can rapidly progress. This study aimed to construct a machine learning model to predict the risk of TLS using clinical indicators at the time of ALL diagnosis. Methods: This observational cohort study was conducted at the National Clinical Research Center for Child Health and Disease. Data were collected from pediatric ALL patients diagnosed between December 2008 and December 2021. Four machine learning models were constructed using the Least Absolute Shrinkage and Selection Operator (LASSO) to select key clinical indicators for model construction. Results: The study included 2,243 pediatric ALL patients, and the occurrence of TLS was 8.87%. A total of 33 indicators with missing values ≤30% were collected, and 12 risk factors were selected through LASSO regression analysis. The CatBoost model with the best performance after feature screening was selected to predict the TLS of ALL patients. The CatBoost model had an AUC of 0.832 and an accuracy of 0.758. The risk factors most associated with TLS were the absence of potassium, phosphorus, aspartate transaminase (AST), white blood cell count (WBC), and urea levels. Conclusion: We developed the first TLS prediction model for pediatric ALL to assist clinicians in risk stratification at diagnosis and in developing personalized treatment protocols. This study is registered on the China Clinical Trials Registry platform (ChiCTR2200060616). Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2200060616.

Memory/active T cell activation is associated with immunotherapeutic response in fumarate hydratase-deficient renal cell carcinoma.

PURPOSE: Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and lethal subtype of kidney cancer. However, the optimal treatments and molecular correlates of benefits for FH-deficient RCC are currently lacking. EXPERIMENTAL DESIGN: A total of 91 patients with FH-deficient RCC from 15 medical centers between 2009 and 2022 were enrolled in this study. Genomic and bulk RNA sequencing (RNA-seq) were performed on 88 and 45 untreated FH-deficient RCCs, respectively. Single-cell RNA-seq was performed to identify biomarkers for treatment response. Main outcomes included disease-free survival (DFS) for localized patients, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for metastatic patients. RESULTS: In the localized setting, we found that a cell cycle progression signature enabled to predict disease progression. In the metastatic setting, first-line immune checkpoint inhibitor plus tyrosine kinase inhibitor (ICI+TKI) combination therapy showed satisfactory safety and was associated with a higher ORR (43.2% vs. 5.6%), apparently superior PFS (median PFS: 17.3 vs. 9.6 months, P=0.016) and OS (median OS: not reached vs. 25.7 months, P=0.005) over TKI monotherapy. Bulk and single-cell RNA-seq data revealed an enrichment of memory and effect T cells in responders to ICI plus TKI combination therapy. Furthermore, we identified a signature of memory and effect T cells that was associated with the effectiveness of ICI plus TKI combination therapy. CONCLUSIONS: ICI plus TKI combination therapy may represent a promising treatment option for metastatic FH-deficient RCC. A memory/active T cell-derived signature is associated with the efficacy of ICI+TKI but necessitates further validation.

Capecitabine/cisplatin combined with concurrent intensity-modulated radiation therapy: a feasible therapeutic strategy for anal squamous cell carcinoma

Purpose To evaluate the efficacy and safety of capecitabine/cisplatin (XP) combined with intensity-modulated radiation therapy (IMRT) in patients with non-metastatic anal squamous cell carcinoma (ASCC). Method and materials All patients with ASCC who received radical concurrent chemoradiotherapy in the past 8 years were screened. Patients who received XP or mitomycin/5-fluorouracil (MF) were selected and analyzed retrospectively. Results ASCC is an uncommon cancer, there were 36 patients were included in our study. The XP group and MF group included 18 patients each. The clinical complete response (cCR) rates in the XP group and the MF group were 94.4% and 88.9%, respectively (P = 1). The 2-year local control (LC), disease-free survival (DFS), and colostomy-free survival (CFS) rates were higher in the XP group than in the MF group (100% vs 93.3%, P = 0.32). Hematologic toxicities, especially grade ≥ 3 leukopenia (11.1% vs 44.4%, P = 0.06) and neutropenia (5.6% vs 61.1%, P = 0.001), were lower in the XP group than MF group. As a result of fewer side effects, fewer patients in the XP group demanded the dose reduction of chemotherapy (11.1% vs 50%, P = 0.03) and radiation interruption (55.6% vs 77.8%, P = 0.289). Delayed radiotherapy was shorter in the XP group (2.5 vs 6.5 days, P = 0.042) than in the MF group. Conclusion The XP regimen was as effective as the MF regimen in non-metastatic ASCC. Compared with the standard MF regimen, XP combined with IMRT showed higher treatment completion and lower toxicities. It could be considered a feasible alternative for patients with non-metastatic ASCC (AU)

Energy-guided diffusion model for CBCT-to-CT synthesis.

Cone Beam Computed Tomography (CBCT) plays a crucial role in Image-Guided Radiation Therapy (IGRT), providing essential assurance of accuracy in radiation treatment by monitoring changes in anatomical structures during the treatment process. However, CBCT images often face interference from scatter noise and artifacts, posing a significant challenge when relying solely on CBCT for precise dose calculation and accurate tissue localization. There is an urgent need to enhance the quality of CBCT images, enabling a more practical application in IGRT. This study introduces EGDiff, a novel framework based on the diffusion model, designed to address the challenges posed by scatter noise and artifacts in CBCT images. In our approach, we employ a forward diffusion process by adding Gaussian noise to CT images, followed by a reverse denoising process using ResUNet with an attention mechanism to predict noise intensity, ultimately synthesizing CBCT-to-CT images. Additionally, we design an energy-guided function to retain domain-independent features and discard domain-specific features during the denoising process, enhancing the effectiveness of CBCT-CT generation. We conduct numerous experiments on the thorax dataset and pancreas dataset. The results demonstrate that EGDiff performs better on the thoracic tumor dataset with SSIM of 0.850, MAE of 26.87 HU, PSNR of 19.83 dB, and NCC of 0.874. EGDiff outperforms SoTA CBCT-to-CT synthesis methods on the pancreas dataset with SSIM of 0.754, MAE of 32.19 HU, PSNR of 19.35 dB, and NCC of 0.846. By improving the accuracy and reliability of CBCT images, EGDiff can enhance the precision of radiation therapy, minimize radiation exposure to healthy tissues, and ultimately contribute to more effective and personalized cancer treatment strategies.

Bladder sparing by short-course radiotherapy combined with toripalimab in high-risk/extremely high-risk non-muscle invasive bladder cancer (HOPE-04): study protocol for a single-arm, prospective, phase II trial.

INTRODUCTION: Radical cystectomy remains the standard treatment for intravesical Bacille Calmette-Guerin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC) because potential bladder-preserving therapies are not well established. Combination of radiotherapy with programmed death-1 (PD-1) antibody may offer an optional bladder preservation treatment for high-risk/extremely high risk NMIBC. Hence, the current study aims to investigate the safety and efficacy of short-course radiotherapy (5×5 Gy) and toripalimab (PD-1 antibody) as a novel bladder sparing treatment in this population. METHODS AND ANALYSIS: HOPE-04 is an open-label, single-arm, phase II study, designed to evaluate the safety and efficacy of short-course radiotherapy and toripalimab in patients with high-risk/extremely high risk NMIBC. Fifty-five patients with pathological and imaging diagnosed NMIBC with or without BCG treatment will be recruited. Radiotherapy of 5×5 Gy will be given to the whole bladder followed by a focal tumour bed boost and concomitant administration of toripalimab of 240 mg intravenous infusion every 21 days for 12 cycles (about 1 year). The primary endpoints are disease-free survival and safety. The secondary endpoint is overall survival. Additional indicators include implementation rate of salvage surgery and quality of life. ETHICS AND DISSEMINATION: This trial has been approved by the Ethics Committee of West China Hospital, Sichuan University. Trial findings will be disseminated via peer reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: Chinese Ethics Committee of Registering Clinical Trials (ChiCTR2200059970).

Capecitabine/cisplatin combined with concurrent intensity-modulated radiation therapy: a feasible therapeutic strategy for anal squamous cell carcinoma.

PURPOSE: To evaluate the efficacy and safety of capecitabine/cisplatin (XP) combined with intensity-modulated radiation therapy (IMRT) in patients with non-metastatic anal squamous cell carcinoma (ASCC). METHOD AND MATERIALS: All patients with ASCC who received radical concurrent chemoradiotherapy in the past 8 years were screened. Patients who received XP or mitomycin/5-fluorouracil (MF) were selected and analyzed retrospectively. RESULTS: ASCC is an uncommon cancer, there were 36 patients were included in our study. The XP group and MF group included 18 patients each. The clinical complete response (cCR) rates in the XP group and the MF group were 94.4% and 88.9%, respectively (P = 1). The 2-year local control (LC), disease-free survival (DFS), and colostomy-free survival (CFS) rates were higher in the XP group than in the MF group (100% vs 93.3%, P = 0.32). Hematologic toxicities, especially grade ≥ 3 leukopenia (11.1% vs 44.4%, P = 0.06) and neutropenia (5.6% vs 61.1%, P = 0.001), were lower in the XP group than MF group. As a result of fewer side effects, fewer patients in the XP group demanded the dose reduction of chemotherapy (11.1% vs 50%, P = 0.03) and radiation interruption (55.6% vs 77.8%, P = 0.289). Delayed radiotherapy was shorter in the XP group (2.5 vs 6.5 days, P = 0.042) than in the MF group. CONCLUSION: The XP regimen was as effective as the MF regimen in non-metastatic ASCC. Compared with the standard MF regimen, XP combined with IMRT showed higher treatment completion and lower toxicities. It could be considered a feasible alternative for patients with non-metastatic ASCC.

Visible-Light-Promoted Regioselective Hydroborylation of Ketene Dithioacetals with NHC-Boranes.

NHC-boranes have been treated as a reliable source of boryl radicals. In this study, regioselective hydroborylation of ketene dithioacetals with NHC-borane was achieved under mild conditions via a visible-light-promoted radical chain process using thiophenol as a proton donor and hydrogen atom transfer. This protocol features a low-cost catalyst, good functional group tolerance, a relatively broad range of substrate scope, and good to excellent yields. Moreover, mechanism of this hydroborylation reaction was preliminarily studied.

Preformed Pt Nanoparticles Supported on Nanoshaped CeO2 for Total Propane Oxidation.

Pt-based catalysts have been widely used for the removal of short-chain volatile organic compounds (VOCs), such as propane. In this study, we synthesized Pt nanoparticles with a size of ca. 2.4 nm and loaded them on various fine-shaped CeO2 with different facets to investigate the effect of CeO2 morphology on the complete oxidation of propane. The Pt/CeO2-o catalyst with {111} facets exhibited superior catalytic activity compared to the Pt/CeO2-r catalyst with {110} and {100} facets. Specifically, the turnover frequency (TOF) value of Pt/CeO2-o was 1.8 times higher than that of Pt/CeO2-r. Moreover, Pt/CeO2-o showed outstanding long-term stability during 50 h. X-ray photoelectron spectroscopy (XPS) and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) revealed that the excellent performance of Pt/CeO2-o is due to the prevalence of metallic Pt species, which promotes C-C bond cleavage and facilitates the rapid removal of surface formate species. In contrast, a stronger metal-support interaction in Pt/CeO2-r leads to easier oxidation of Pt species and the accumulation of intermediates, which is detrimental to the catalytic activity. Our work provides insight into the oxidation of propane on different nanoshaped Pt/CeO2 catalysts.

Genomic and transcriptomic features between primary and paired metastatic fumarate hydratase-deficient renal cell carcinoma.

BACKGROUND: Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is a rare highly aggressive subtype of kidney cancer for which the distinct genomic, transcriptomic, and evolutionary relationships between metastatic and primary lesions are still unclear. METHODS: In this study, whole-exome, RNA-seq, and DNA methylation sequencing were performed on primary-metastatic paired specimens from 19 FH-RCC cases, including 23 primary and 35 matched metastatic lesions. Phylogenetic and clonal evolutionary analyses were used to investigate the evolutionary characteristics of FH-RCC. Transcriptomic analyses, immunohistochemistry, and multiple immunofluorescence experiments were performed to identify the tumor microenvironmental features of metastatic lesions. RESULTS: Paired primary and metastatic lesions generally showed similar characteristics of tumor mutation burden, tumor neoantigen burden, microsatellite instability score, CNV burden, and genome instability index. Notably, we identified an FH-mutated founding MRCA (the most recent common ancestor) clone that dominated the early evolutionary trajectories in FH-RCC. Although both primary and metastatic lesions manifested high immunogenicity, metastatic lesions exhibited higher enrichment of T effector cells and immune-related chemokines, together with upregulation of PD-L1, TIGIT, and BTLA. In addition, we found that concurrent NF2 mutation may be associated with bone metastasis and upregulation of cell cycle signature in metastatic lesions. Furthermore, although in FH-RCC metastatic lesions in general shared similar CpG island methylator phenotype with primary lesions, we found metastatic lesions displaying hypomethylated chemokine and immune checkpoints related genomic loci. CONCLUSIONS: Overall, our study demonstrated the genomic, epigenomic, and transcriptomic features of metastatic lesions in FH-RCC and revealed their early evolutionary trajectory. These results provided multi-omics evidence portraying the progression of FH-RCC.

Delineation of clinical target volume and organs at risk in cervical cancer radiotherapy by deep learning networks.

PURPOSE: Delineation of the clinical target volume (CTV) and organs-at-risk (OARs) is important in cervical cancer radiotherapy. But it is generally labor-intensive, time-consuming, and subjective. This paper proposes a parallel-path attention fusion network (PPAF-net) to overcome these disadvantages in the delineation task. METHODS: The PPAF-net utilizes both the texture and structure information of CTV and OARs by employing a U-Net network to capture the high-level texture information, and an up-sampling and down-sampling (USDS) network to capture the low-level structure information to accentuate the boundaries of CTV and OARs. Multi-level features extracted from both networks are then fused together through an attention module to generate the delineation result. RESULTS: The dataset contains 276 computed tomography (CT) scans of patients with cervical cancer of staging IB-IIA. The images are provided by the West China Hospital of Sichuan University. Simulation results demonstrate that PPAF-net performs favorably on the delineation of the CTV and OARs (e.g., rectum, bladder and etc.) and achieves the state-of-the-art delineation accuracy, respectively, for the CTV and OARs. In terms of the Dice Similarity Coefficient (DSC) and the Hausdorff Distance (HD), 88.61% and 2.25 cm for the CTV, 92.27% and 0.73 cm for the rectum, 96.74% and 0.68 cm for the bladder, 96.38% and 0.65 cm for the left kidney, 96.79% and 0.63 cm for the right kidney, 93.42% and 0.52 cm for the left femoral head, 93.69% and 0.51 cm for the right femoral head, 87.53% and 1.07 cm for the small intestine, and 91.50% and 0.84 cm for the spinal cord. CONCLUSIONS: The proposed automatic delineation network PPAF-net performs well on CTV and OARs segmentation tasks, which has great potential for reducing the burden of radiation oncologists and increasing the accuracy of delineation. In future, radiation oncologists from the West China Hospital of Sichuan University will further evaluate the results of network delineation, making this method helpful in clinical practice.

Multidisciplinary Team (MDT) Discussion Improves Overall Survival Outcomes for Metastatic Renal Cell Carcinoma Patients.

Purpose: Multidisciplinary team (MDT) discussion is a widely used model to manage patients diagnosed with cancer. However, there has been no direct evidence to prove its effect on the prognosis of metastatic renal cell carcinoma (mRCC) patients, so this study explored the impact of MDT discussion on mRCC patient survival. Methods: The clinical data of 269 mRCC patients were retrospectively collected from 2012 to 2021. The cases were grouped into the MDT and non-MDT groups, then subgroup analysis was performed according to different histology types, as well as exploring the role of MDT in patients who have undergone multiple-line therapy. Overall survival (OS) and progression free survival (PFS) were set as the study endpoint. Results: Approximately half (48.0%, 129/269) of the patients were in the MDT group, with univariable survival analyses showing these patients had remarkably longer median OS (MDT group: 73.7 months; non-MDT group: 33.2 months, hazard ratio (HR): 0.423 (0.288, 0.622), p<0.001) and longer median PFS (MDT group: 16.9 months, non-MDT group: 12.7 months, HR: 0.722 (0.542, 0.962), p=0.026). Furthermore, MDT management resulted in longer survival for both ccRCC and non-ccRCC subgroups. Patients in the MDT group were more likely to receive multi-line therapy (MDT group: 79/129, 61.2% vs non-MDT group: 56/140, 40.0%, p<0.001), and within this patient group, MDT management still resulted in longer OS (MDT group: 94.0 months; non-MDT group: 43.5 months, p=0.009). Conclusion: MDT is associated with prolonged overall survival in mRCC independent of histology, ensuring that patients receive better management and precise treatment.

RC48-ADC combined with tislelizumab as neoadjuvant treatment in patients with HER2-positive locally advanced muscle-invasive urothelial bladder cancer: a multi-center phase Ib/II study (HOPE-03).

Background: Bladder cancer with high expression of human epidermal growth factor receptor-2 (HER2) is related to pathological malignancy and poor prognosis. The standard care for muscle-invasive urothelial bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with pelvic lymph node dissection. For HER2-positive MIBC, the efficacy of cisplatin-based NAC is unsatisfactory, and adverse reactions are inevitable or even intolerable. New regimens with higher efficiency and lower toxicity need to be explored in the neoadjuvant setting for this population. Methods: HOPE-03 is a multi-center, open-label, single-arm, phase Ib/II study aiming to evaluate the safety and efficacy of RC48-ADC (disitamab vedotin (DV)), a humanized anti-HER2 antibody conjugated with monomethyl auristatin E, and tislelizumab (PD-1 antibody) as a novel neoadjuvant treatment combination in patients with HER2-positive locally advanced urothelial MIBC. Fifty-one patients with cT2-4bN0-3M0-1a pathology- and imaging-diagnosed HER2 positive (immunohistochemistry status 3+ or 2+ or 1+) MIBC were recruited. Of these patients, six were enrolled in the dose-escalation phase (three patients in the RC48-ADC 1.5 mg/kg group and three patients in the 2.0 mg/kg group), and 45 patients were enrolled in the phase II study (the expected recommended phase II dose for RC48-ADC was 2.0 mg/kg). Patients without disease progression received radical cystectomy or bladder-sparing therapies as their preference after neoadjuvant treatment. The primary endpoints were clinical complete remission rate (cCR rate; T0/Ta/Tis), pathological complete remission rate (pCR rate), and safety. The secondary endpoints were overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and quality of life. Discussion: The HOPE-03 trial provides a description of the safety profile of RC-48 and tislelizumab combination in the neoadjuvant treatment of HER2-positive locally advanced urothelial MIBC, and the efficacy is explored as well in this population. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=137111, identifier ChiCTR2200060153.

Long-Term Follow-Up Results of Adjuvant Intensity-Modulated Radiotherapy with Concurrent Paclitaxel and Cisplatin in High-Risk Endometrial Cancer Patients.

Purpose: The purpose of this study was to retrospectively review the outcomes of patients with high-risk endometrial cancer treated with adjuvant radiotherapy with concurrent paclitaxel and cisplatin (TP). Methods: Patients with endometrial cancer who underwent radical surgery were screened between Jan 2005 and Dec 2018. Patients with high-risk factors who received adjuvant chemoradiotherapy were included in the study. High risks included stage I, endometrioid-type grade 3 with deep myometrial invasion or lymphovascular space invasion (or both), endometrioid-type stage II to IVa, or stage I to III with serous or clear cell histology. The adjuvant treatment regimen included one cycle of TP chemotherapy, followed by pelvic intensity-modulated radiotherapy (IMRT) with concurrent TP, followed by an additional one cycle of TP. Failure free survival (FFS) and overall survival (OS) were estimated. Patterns of recurrence and occurrence of adverse events were described. Results: A total of 450 patients with high-risk endometrial cancer were screened, 231 of whom were included in this study. After a median follow-up of 70 months, the 5-year OS was 94.7%, and the 6-year OS was 91.8%. The 5-y and 6-y FFS were 90.8% and 87.9%, respectively, which were related to stage (P < 0.05). A total of 14 patients experienced tumor recurrence, including 7 pelvic recurrence and 7 distant metastases. Seven patients died, all due to tumor progression. A total of 164 patients (71%) completed the prescribed course of treatment. A total of 205 patients had adverse events, 46 patients (20%) had grade 1, 92 patients (40%) had grade 2, 49 patients (21%) had grade 3, and 18 patients (8%) had grade 4. There were 83 nonhematologic and 122 hematologic toxicities (26 grade 3 and 18 grade 4). Conclusion: Adjuvant pelvic radiotherapy combined with synchronous TP chemotherapy can achieve excellent long-term survival for high-risk endometrial cancer patients. Moreover, this combination therapy has good safety and feasibility, which is worthy of further study and verification.

Poor treatment responses were related to poor outcomes in pediatric B cell acute lymphoblastic leukemia with KMT2A rearrangements.

BACKGROUND: The KMT2A gene, formerly named the MLL gene, is rearranged (KMT2Ar) in 70-75% of infants, 5-6% of children and 10-15% of adult patients with B cell acute lymphoblastic leukemia (B-ALL). The outcome after chemotherapy of pediatric cases remains poor, and only a few studies have investigated the clinical and laboratory features, treatment response and prognosis in Chinese populations. METHODS: A total of 48 B-ALL children with KMT2Ar were enrolled in the study, and clinical and laboratory data were collected and analyzed by age group. The relationship between prognosis and traditional risk factors and treatment response was investigated for these patients who received chemotherapy. RESULTS: The 48 enrolled patients included 28 males and 20 females; 18 (37.50%) or 30 (62.50%) patients were an age of < 12 m (infant B-ALL) or of > 12 m at onset. An initial WBC count of 300 × 109/L was detected in 7 (14.58%) patients; testicular leukemia (TL) or central nervous system involvement was found in 5 (10.41%) or 3 (6.25%) patients, respectively. Statistical differences were not found in the age groups of sex or initial WBC count, whereas TL was more common in the infant group (P < 0.05). 11q23 was detected in 18 patients; KMT2Ar was detected in 46 (95.83%) or 45 (93.75%) patients by FISH or multiplex RT-PCR technology, respectively; RNA-seq data were obtained for 18 patients, and 3 patients with uncommon KMT2Ar were identified. KMT2A-AFF1, KMT2A-MLLT3 and KMT2A-MLLT1 were the most common transcripts. Statistical differences were not found in treatment response by age groups, including dexamethasone induction, bone marrow (BM) smear status and minimal residual disease (MRD) level at different time points (TP), treatment-related mortality (TRM), or complete remission (CR) rate (P > 0.05); MRD levels monitored by FCM or PCR were unequal at the same TP. Four patients died of treatment, and TRM was 8.33%; 40 patients achieved CR, and the CR rate for the cohort was 83.33%. Seven patients quit, 15 patients relapsed, and the 5 yr cumulative relapse rate was 59.16 ± 9.16%; the 5 yr prospective EFS (pEFS) for patients who were included or excluded from the TRM group was 36.86 ± 8.48% or 40.84 ± 9.16%, respectively. Multivariate analysis for prognosis and hazard ratio was performed for 37 patients without TRM and revealed that an initial WBC count of > 300 × 109/L and a positive level of FCM-MRD were strongly related to a poor outcome for B-ALL patients with KMT2Ar (P < 0.05).

Efficacy of second-line ICIs combined with TKIs among patients with metastatic renal cell carcinoma: a real-world study.

Aim: To evaluate the efficacy of immune checkpoint inhibitors (ICIs) plus tyrosine kinase inhibitors (TKIs) as second-line treatment in patients with metastatic renal cell carcinoma (mRCC). Patients & methods: Baseline and follow-up data from patients with mRCC treated with second-line ICIs plus TKIs or TKIs alone from a single institution were retrospectively gathered. Results: A total of 110 patients were included. The objective response rate was higher among patients treated with ICIs plus TKIs than those treated with TKIs alone (36.5 vs 12.1%; p = 0.002). Treatment with ICIs plus TKIs was associated with longer progression-free survival (15.0 vs 9.0 months; p = 0.009) and overall survival (not reached vs 16.0 months; p = 0.018) than TKI monotherapy. The survival rates at 2 (83.0 vs 74.4%; p = 0.426) and 3 years (58.1 vs 47.5%; p = 0.214) between the two groups were not statistically different. Notably, patients with certain clinicopathological features tended to gain more survival benefits with combined therapy. Conclusion: ICIs plus TKIs showed superior progression-free survival time and tumor response rate over TKIs alone as second-line treatment in patients with mRCC. Future randomized prospective trials are necessary to validate these preliminary findings.

Aim: To evaluate the efficacy of immune checkpoint inhibitors (ICIs) combined with tyrosine kinase inhibitors (TKIs) in patients with previously treated metastatic renal cell carcinoma (mRCC). Patients & methods: Data at initial treatment and follow-up of patients with mRCC with second-line ICIs plus TKIs or TKIs alone were documented. Results: A total of 110 patients were included. The tumor shrinkage rate was higher among patients treated with ICIs plus TKIs than those treated with TKIs alone. Patients receiving ICIs plus TKIs had delayed disease progression and longer survival time compared with patients treated with TKI monotherapy. However, patients had a similar probability of survival after 2 and 3 years of treatment. Notably, patients with certain clinicopathological characteristics gained more survival benefits from ICIs plus TKIs. Conclusion: ICIs plus TKIs showed superior efficacy over TKIs alone in previously treated patients with mRCC. Future randomized prospective trials are necessary to validate these preliminary findings.

Timing theory continuous nursing, resistance training: Rehabilitation and mental health of caregivers and stroke patients with traumatic fractures.

BACKGROUND: Stroke is the leading cause of adult lifelong disability worldwide. A stroke is an acute cerebrovascular disease with a variety of causes and corresponding clinical symptoms. Around 75% of surviving stroke patients experience impaired nerve function, and some suffer from traumatic fractures, which can lead to special care needs. AIM: To determine the effect of timing theory continuous care, with resistance training, on the rehabilitation and mental health of caregivers and stroke patients with traumatic fractures. METHODS: Between January 2017 to March 2021, we selected 100 hospital admissions with post-stroke hemiplegia complicated with a traumatic fracture. Two participant groups were created: (1) Control group: given resistance training; and (2) Observation group: given timing theory continuous care combined with resistance training. The degree of satisfaction and differences in bone and phosphorus metabolism indexes between the two groups were compared. The self-perceived burden scale (SPBS) and caregiver burden questionnaire were used to evaluate the psychological health of patients and caregivers. The Harris hip function score, ability of daily living (ADL) scale, and global quality of life questionnaire (GQOL-74) were used to evaluate hip function, ability of daily living, and quality of life. RESULTS: Data were collected prior to and after intervention. Alkaline phosphatase (ALP), osteocalcin, and vitamin D3 in the observation group and control group increased after intervention (P < 0.05), and carboxy-terminal peptide of type I collagen ß Special sequence (ß-CTX) decreased (P < 0.05). ALP and osteocalcin in the observation group were higher than in the control group (P < 0.05). There was no significant difference in ß-CTX and vitamin D3 between the two groups (P > 0.05). The SPBS score of the observation group was lower and the ADL score was higher than the control group. The burden score was lower and the Harris hip function and GQOL-74 scores were higher than that of the control group (P < 0.05). The observation group's satisfaction rating was 94.00%, which was higher than the rating from the control group (P < 0.05). CONCLUSION: Timing theory continuous nursing with resistance training can reduce hip dysfunction in stroke patients with a traumatic fracture and enhance quality of life and mental health of patients and caregivers.

The long-term outcome and risk factors for precursor B cell acute lymphoblastic leukemia without specific fusion genes in Chinese children: experiences from multiple centers.

Specific fusion genes play important roles as risk factors for strategic treatment in pediatric B-cell acute lymphoblastic leukemia (B-ALL), and the risk factors in patients without common fusion genes have not been well demonstrated. We collected and analyzed clinical and laboratory findings, treatment responses and outcomes in B-ALL patients without specific fusion genes. Whole-exome sequencing (WES) and/or RNA sequencing (RNAseq) data from bone marrow relapsed patients were also analyzed. 283 patients were enrolled in the study. Traditional elements and treatment responses at different time points (TPs) were evaluated to classify risk groups and adjust the treatment strategy. Treatment-related mortality was found in 11 (3.89%) patients, 49 (17.31%) patients relapsed, and the ten-year prospective event-free survival (pEFS) was 78.2±2.5%. Univariate analysis revealed that significant differences were not found in the pEFS of traditional risk factors, including sex, age, WBC count or chromosome status; good responses of BM smears at TP1 and minimal residual disease (MRD) levels at TP2 and TP3 were strongly associated with prolonged pEFS. Compared with the IR or the HR group, patients in the SR group presented with longer pEFS and a lower relapse rate. Multivariable analysis of outcomes and hazard ratios revealed that a positive MRD level was a key risk factor. WES or RNAseq was performed for BM relapse patients, and adverse and unreported genetic abnormalities were discovered. Favorable outcomes were acquired in the cohort. The study results showed that traditional risk factors and poor prednisone response were overcome by modified chemotherapy, and a positive MRD level was a key risk factor in these patients. NGS is needed to discover more risk-related molecular abnormalities.

Prognostic significance of measurable residual disease based on multiparameter flow cytometry in childhood acute myeloid leukemia. / åŸºäºŽæµå¼ç»†èƒžæœ¯çš„å¯æµ‹é‡æ®‹ç•™ç— å¯¹å„¿ç«¥æ€¥æ€§é«“ç³»ç™½è¡€ç— é¢„åŽæ„ä¹‰çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To study the prognostic value of measurable residual disease (MRD) for childhood acute myeloid leukemia (AML) by analyzing MRD-guided risk stratification therapy. METHODS: A total of 93 children with AML were prospectively enrolled in this study. Chemotherapy with the 2015-AML-03 regimen was completed according to the risk stratification determined by genetic abnormality at initial diagnosis and MRD and bone marrow cytology after induction therapy I. Multiparameter flow cytometry was used to dynamically monitor MRD and analyze the prognostic effect of MRD on 3-year cumulative incidence of recurrence (CIR) rate, event-free survival (EFS) rate, and overall survival (OS) rate. RESULTS: The 93 children with AML had a 3-year CIR rate of 48%±6%, a median time to recurrence of 11 months (range 2-32 months), a 3-year OS rate of 65%±6%, and a 3-year EFS rate of 50%±5%. After induction therapy I and intensive therapy I, the MRD-positive children had a significantly higher 3-year CIR rate and significantly lower 3-year EFS and OS rates than the MRD-negative children (P<0.05). There were no significant differences in 3-year CIR, EFS, and OS rates between the MRD-positive children with a low risk at initial diagnosis and the MRD-negative children after adjustment of chemotherapy intensity (P>0.05). The multivariate analysis showed that positive MRD after intensive treatment I was a risk factor for 3-year OS rate in children with AML (P<0.05). CONCLUSIONS: MRD has predictive value for the prognosis of children with AML. Based on the MRD-guided risk stratification therapy, reasonable application of chemotherapy may improve the overall prognosis of children with AML.

Synchronous Rectal Tumours with Different Molecular and Genetic Phenotypes Occurring in a Patient with Lynch Syndrome.

The increasingly widespread use of immunohistochemistry and next-generation sequencing (NGS) in the detection of microsatellite instability (MSI) and DNA mismatch repair (MMR) status has led to the observation of various unusual tumour types that exhibit MMR protein deficiency in Lynch syndrome (LS). Here, we report a case of two synchronous colorectal cancer (CRC) tumours simultaneously occurring in a 42-year-old woman with a deleterious germline mutation in MSH6, abundant expression of PD-L1 and high tumour mutation burden (TMB). The two CRC tumours (tumours A and B) harboured highly heterogeneous features. One showed loss of MSH6 protein and a microsatellite stable (MSS)/MSI-low (MSI-L) status, while the other presented no loss of MMR protein and MSI-H status. Furthermore, the 9 common mutated genes between the two CRC tumours had no shared mutation sites. Only 4 KEGG pathways were identified as enriched for five of the common mutated genes, while 8 cancer-related pathways were identified as enriched for 9 and 13 unique mutated genes in tumours A and B, respectively. Therefore, we chose immune checkpoint inhibitors (ICIs) as the potential therapy. This case exemplifies the complexity of tumorigenesis and potential ICI treatment in LS patients.