Human papillomavirus infection affects treatment outcomes and the immune microenvironment in patients with advanced penile squamous cell carcinoma receiving programmed cell death protein 1 inhibitor-based combination therapy.

BACKGROUND: Penile squamous cell carcinoma (PSCC) is a human papillomavirus (HPV)-associated malignancy. Immunotherapy is emerging as a potential treatment for advanced PSCC. In this study, the authors analyzed the association of HPV status with outcomes and the immune microenvironment in patients with advanced PSCC undergoing programmed cell death protein 1 (PD1) inhibitor-based combination therapy (PCT). METHODS: HPV status was assessed using quantitative polymerase chain reaction in 87 patients with advanced PSCC treated with PCT. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in the HPV+ and HPV- groups were compared. Additionally, bulk RNA sequencing was performed to investigate the potential impact of HPV on the immune microenvironment in advanced PSCC. RESULTS: Among patients receiving first-line PCT, ORR (91.7% vs. 64.6%, p = .014) and DCR (100.0% vs. 79.2%, p = .025) in the HPV+ group were higher compared to the HPV- group. Kaplan-Meier curves demonstrated that the HPV+ group exhibited superior PFS (p = .005) and OS (p = .004) for patients in the first-line setting. However, these advantages of HPV infection were not observed in multi-line PCT (p > .050). HPV status remained an independent prognostic factor for predicting better ORR (p = .024), PFS (p = .002), and OS (p = .020) in the multivariate analyses. Landmark analyses showed that the HPV-induced superiority of PFS occurred at an early stage (within 3 months) and OS occurred at a relatively late stage (within 9 months). Bioinformatic analyses identified potential immune-activated genes (GLDC, CYP4F12, etc.) and pathways (RAGE, PI3K/AKT, etc.), antitumor immune cell subtypes, and lower tumor immune dysfunction and exclusion scores in HPV+ tissues. CONCLUSIONS: HPV infection may confer treatment efficacy and survival benefits in patients with advanced PSCC receiving first-line PCT because of the possible stimulation of the antitumor immune microenvironment. PLAIN LANGUAGE SUMMARY: Human papillomavirus (HPV) infection may induce better objective response rate, progression-free survival (PFS), and overall survival (OS) for advanced penile squamous cell carcinoma (PSCC) patients receiving first-line programmed cell death protein 1 inhibitor-based combination therapy (PCT) instead of multi-line PCT. HPV infection-induced PFS advantage occurs at an early stage (within 3 months) whereas OS superiority occurs at a relatively late stage (within 9 months). Antitumor immune microenvironment could be stimulated by HPV infection in advanced PSCC tissues.

A real-world observation on thrombopoietic agents for patients with cancer treatment-induced thrombocytopenia in China: A multicenter, cross-sectional study.

BACKGROUND: Studies on various thrombopoietic agents for cancer treatment-induced thrombocytopenia (CTIT) in China are lacking. This study aimed to provide detailed clinical profiles to understand the outcomes and safety of different CTIT treatment regimens. METHODS: In this retrospective, cross-sectional study, 1664 questionnaires were collected from 33 hospitals between March 1 and July 1, 2021. Patients aged >18 years were enrolled who were diagnosed with CTIT and treated with recombinant interleukin 11 (rhIL-11), recombinant thrombopoietin (rhTPO), or a thrombopoietin receptor agonist (TPO-RA). The outcomes, compliance, and safety of different treatments were analyzed. RESULTS: Among the 1437 analyzable cases, most patients were treated with either rhTPO alone (49.3%) or rhIL-11 alone (27.0%). The most common combination regimen used was rhTPO and rhIL-11 (10.9%). Platelet transfusions were received by 117 cases (8.1%). In multivariate analysis, rhTPO was associated with a significantly lower proportion of platelet recovery, platelet transfusion, and hospitalization due to chemotherapy-induced thrombocytopenia (CIT) than rhIL-11 alone. No significant difference was observed in the time taken to achieve a platelet count of >100 × 109/L and chemotherapy dose reduction due to CIT among the different thrombopoietic agents. The outcomes of thrombocytopenia in 170 patients who received targeted therapy and/or immunotherapy are also summarized. The results show that the proportion of platelet recovery was similar among the different thrombopoietic agents. No new safety signals related to thrombopoietic agents were observed in this study. A higher proportion of physicians preferred to continue treatment with TPO-RA alone than with rhTPO and rhIL-11. CONCLUSIONS: This survey provides an overview of CTIT and the application of various thrombopoietic agents throughout China. Comparison of monotherapy with rhIL-11, rhTPO, and TPO-RA requires further randomized clinical trials. The appropriate application for thrombopoietic agents should depend on the pretreatment of platelets, treatment variables, and risk of bleeding. PLAIN LANGUAGE SUMMARY: To provide an overview of the outcome of cancer treatment-induced thrombocytopenia in China, our cross-sectional study analyzed 1437 cases treated with different thrombopoietic agents. Most of the patients were treated with recombinant interleukin 11 (rhIL-11) and recombinant thrombopoietin (rhTPO). rhTPO was associated with a significantly lower proportion of platelet recovery and platelet transfusion compared with rhIL-11.

Optimal Sequential Strategies for Antibody-Drug Conjugate in Metastatic Breast Cancer: Evaluating Efficacy and Cross-Resistance.

BACKGROUND: The optimal sequential strategy for antibody-drug conjugates (ADCs) in breast cancer remains uncertain. This study aimed to evaluate the efficacy and potential resistance of second ADC (ADC2) following the first ADC (ADC1) in human epidermal growth factor receptor 2 (HER2)-positive and HER2-low MBC. METHODS: This retrospective, multicenter, real-world study enrolled patients with MBC who received at least 2 different types of ADCs in 3 hospitals in China between July 1, 2017 and May 1, 2023. Outcomes included the objective response rate (ORR) for ADC1 and ADC2, progression free survival 2 (PFS2), defined as the time from initiation of ADC2 to progression, and overall survival (OS). RESULTS: Seventy-nine female patients were included, 64 of whom had HER2-positive disease. The ORR for ADC2 with similar payload of ADC1 was found to be 5.3%. When switching to a different payload, the ORR of ADC2 increased to 22.6%. The PFS2 for ADC2 remained similar regardless of whether the payload was similar or different. Switching to different payload showed a higher ORR in patients with rapid progression and a durable response longer than 6 months (41.2% vs 15.0%). Specifically, significantly longer PFS2 and OS were seen in patients treated with trastuzumab deruxtecan (T-Dxd) compared to those treated with disitamab vedotin (RC48) after progression from trastuzumab emtansine (T-DM1; median PFS2 5.37 months vs 3.30 months, HR = 0.40, 95% CI 0.17-0.93, P = .034; median OS 50.6 months vs 20.2 months, HR = 0.27, 95% CI 0.08-0.91, P = .034). For patients who progressed after T-Dxd, the median PFS2 was 6.05 months for those treated with RC48 versus 0.93 months for those treated with T-DM1 (HR = 0.03, 95% CI 0.002-0.353, P = .0093). Genomic analysis revealed that alternation of retinoblastoma1 was significantly associated with superior PFS. CONCLUSION: The alternation of payload achieves different responses in different settings. T-Dxd followed by RC48 may be a potentially beneficial strategy in HER2-positive disease. Further research is needed to elucidate the mechanism of cross-resistance.

Temperature-Dependent Color-Tunable Afterglow in Zirconium-Doped CsCdCl3 Perovskite for Advanced Anti-Counterfeiting and Thermal Distribution Detection.

Persistent luminescence (PersL) materials exhibit thermal-favored optical behavior, enabling their unique applications in security night vision signage, in vivo bioimaging, and optical anti-counterfeiting. Therefore, developing efficient and color-tunable PersL materials is significantly crucial in promoting advanced practical use. In this study, hexagonal Zr4+ -doped CsCdCl3 perovskite is synthesized via a hydrothermal reaction with a tunable photoluminescent (PL) behavior through heterovalent substitution. Moreover, the incorporation of Zr4+ ions result in an extra blue emission band, originating from the enhanced excitonic recombination in D3d octahedrons. Furthermore, the afterglow performances of the samples are dramatically improved, along with the noticeable temperature-dependent PersL as well as the thermo-luminescence with tunable color output. Detailed analysis reveals that the unique temperature-dependent PersL and thermo-luminescence color change are attributed to the presence of multiple luminous centers and abundant traps. Overall, this work facilitates the development of optical intelligence platforms and novel thermal distribution probes with the as-developed halides perovskite for its superior explored PersL characteristic.

Effects of MhMYB1 and MhMYB2 transcription factors on the monoterpenoid biosynthesis pathway in l-menthol chemotype of Mentha haplocalyx Briq.

MAIN CONCLUSION: Transcription factors MhMYB1 and MhMYB2 correlate with monoterpenoid biosynthesis pathway in l-menthol chemotype of Mentha haplocalyx Briq, which could affect the contents of ( -)-menthol and ( -)-menthone. Mentha haplocalyx Briq., a plant with traditional medicinal and edible uses, is renowned for its rich essential oil content. The distinct functional activities and aromatic flavors of mint essential oils arise from various chemotypes. While the biosynthetic pathways of the main monoterpenes in mint are well understood, the regulatory mechanisms governing different chemotypes remain inadequately explored. In this investigation, we identified and cloned two transcription factor genes from the M. haplocalyx MYB family, namely MhMYB1 (PP236792) and MhMYB2 (PP236793), previously identified by our research group. Bioinformatics analysis revealed that MhMYB1 possesses two conserved MYB domains, while MhMYB2 contains a conserved SANT domain. Yeast one-hybrid (Y1H) analysis results demonstrated that both MhMYB1 and MhMYB2 interacted with the promoter regions of MhMD and MhPR, critical enzymes in the monoterpenoid biosynthesis pathway of M. haplocalyx. Subsequent virus-induced gene silencing (VIGS) of MhMYB1 and MhMYB2 led to a significant reduction (P < 0.01) in the relative expression levels of MhMD and MhPR genes in the VIGS groups of M. haplocalyx. In addition, there was a noteworthy decrease (P < 0.05) in the contents of ( -)-menthol and ( -)-menthone in the essential oil of M. haplocalyx. These findings suggest that MhMYB1 and MhMYB2 transcription factors play a positive regulatory role in ( -)-menthol biosynthesis, consequently influencing the essential oil composition in the l-menthol chemotype of M. haplocalyx. This study serves as a pivotal foundation for unraveling the regulatory mechanisms governing monoterpenoid biosynthesis in different chemotypes of M. haplocalyx.

Representation of molecules for drug response prediction.

The rapid development of machine learning and deep learning algorithms in the recent decade has spurred an outburst of their applications in many research fields. In the chemistry domain, machine learning has been widely used to aid in drug screening, drug toxicity prediction, quantitative structure-activity relationship prediction, anti-cancer synergy score prediction, etc. This review is dedicated to the application of machine learning in drug response prediction. Specifically, we focus on molecular representations, which is a crucial element to the success of drug response prediction and other chemistry-related prediction tasks. We introduce three types of commonly used molecular representation methods, together with their implementation and application examples. This review will serve as a brief introduction of the broad field of molecular representations.

Persulfidation of transcription factor MYB10 inhibits anthocyanin synthesis in red-skinned pear.

Hydrogen sulfide (H2S) is a gaseous signaling molecule that delays color change during fruit ripening. Whether H2S affects anthocyanin biosynthesis in red-skinned pears (Pyrus L.) remains unclear. Here, we found that H2S substantially inhibits anthocyanin accumulation in red-skinned pears and the expression of several genes encoding transcription factors is affected in response to H2S signaling. For example, PyMYB10 and PyMYB73 were down-regulated, whereas PyMYB114 and PyMYB6 were up-regulated. Bioinformatics analysis showed that PyMYB73 and PyMYB6, each containing an EAR motif, may negatively regulate anthocyanin accumulation. Transient expression analysis showed that PyMYB73 substantially promotes anthocyanin biosynthesis by co-transforming with PyMYB10/PyMYB114 + PybHLH3; however, PyMYB6 inhibited anthocyanin biosynthesis in strawberry (Fragaria vesca) receptacles and pear fruits, and PyMYB73 interacted with PyMYB10 and PyMYB6 but not PyMYB114 or PybHLH3. Further investigation showed that Cys194 and Cys218 of PyMYB10 were modified by persulfidation and that PyMYB10Cys218Ala substantially increased anthocyanin accumulation by a transient transformation system. Co-transformation of PyMYB10Cys218Ala + PyMYB73/PyMYB6 also promoted anthocyanin accumulation in pear fruits. Yeast two-hybrid assays showed that the mutation of PyMYB10 did not affect the interaction between PyMYB10 and PyMYB73, but it inhibited interaction with PyMYB6. Moreover, H2S weakened the interaction between PyMYB10 and PyMYB73 but enhanced the interaction with PyMYB6. Thus, we provided a model in which PyMYB10 undergoes persulfidation at Cys218, enhancing the interaction with PyMYB6 and reducing the interaction with PyMYB73. These subsequently results in lower expression of the anthocyanin biosynthesis-related genes Pyrus dihydroflavonol 4-reductase (PyDFR), Pyrus anthocyanidin synthase (PyANS), Pyrus UDP-glucose: flavonoid 3-glucosyl transferase (PyUFGT) and Pyrus glutathione S-transferase (PyGST), thereby inhibiting anthocyanin accumulation in red-skinned pears. Our findings provided a molecular mechanism for H2S-mediated anthocyanin biosynthesis in red-skinned pears.

STING-dependent trained immunity contributes to host defense against Clostridium perfringens infection via mTOR signaling.

Clostridium perfringens (C. perfringens) infection is recognized as one of the most challenging issues threatening food safety and perplexing agricultural development. To date, the molecular mechanisms of the interactions between C. perfringens and the host remain poorly understood. Here, we show that stimulator of interferon genes (STING)-dependent trained immunity protected against C. perfringens infection through mTOR signaling. Heat-killed Candida albicans (HKCA) training elicited elevated TNF-α and IL-6 production after LPS restimulation in mouse peritoneal macrophages (PM). Although HKCA-trained PM produced decreased levels of TNF-α and IL-6, the importance of trained immunity was demonstrated by the fact that HKCA training resulted in enhanced bacterial phagocytic ability and clearance in vivo and in vitro during C. perfringens infection. Interestingly, HKCA training resulted in the activation of STING signaling. We further demonstrate that STING agonist DMXAA is a strong inducer of trained immunity and conferred host resistance to C. perfringens infection in PM. Importantly, corresponding to higher bacterial burden, reduction in cytokine secretion, phagocytosis, and bacterial killing were shown in the absence of STING after HKCA training. Meanwhile, the high expression levels of AKT/mTOR/HIF1α were indeed accompanied by an activated STING signaling under HKCA or DMXAA training. Moreover, inhibiting mTOR signaling with rapamycin dampened the trained response to LPS and C. perfringens challenge in wild-type (WT) PM after HKCA training. Furthermore, STING­deficient PM presented decreased levels of mTOR signaling-related proteins. Altogether, these results support STING involvement in trained immunity which protects against C. perfringens infection via mTOR signaling.

Iodine-Promoted Thioylation and Dicarbonylation of Enaminone α-C Sites: Synthesis of Fully Substituted Thiazoles via C═C Bond Cleavage.

A novel iodine-promoted difunctionalization of α-C sites in enaminones was demonstrated as a means of synthesizing a variety of fully substituted thiazoles by constructing C-C(CO), C-S, and C-N bonds. This transformation allows the realization of enaminones as unusual aryl C2 synthons and simultaneously allows the thioylation and dicarbonylation of α-C sites. A preliminary mechanistic study was performed and indicated that the cleavage of C═C bonds in enaminones involves a bicyclization/ring-opening and oxidative coupling sequence.

I2-DMSO-Mediated Construction of 2,3- and 2,4-Disubstituted Pyrimido[1,2-b]indazole Skeletons.

An efficient synthetic method for constructing 2,3- and 2,4-disubstituted pyrimidio[1,2-b]indazole skeletons through I2-DMSO-mediated and substrate-controlled regioselective [4 + 2] cyclization is reported. The reaction conditions are mild, its operation is simple, and the substrate scope is wide. More than 60 pyrimidio[1,2-b]indazole derivatives have been synthesized, providing a new methodology for constructing related molecules and potentially enriching bioactive-molecule libraries.

Azide-free cyclization reaction access to 4-aryl-NH-1,2,3-triazoles: P-toluenesulfonyl hydrazide and sulfamic acid as nitrogen sources.

An iodine-mediated cyclization has been developed to 4-aryl-NH-1,2,3-triazoles, with p-toluenesulfonyl hydrazide and sulfamic acid used as nitrogen sources. Sulfamic acid plays a crucial role in this reaction by both acting as a substrate and providing an acidic environment. This reaction offers a metal- and azide-free strategy to access NH-1,2,3-triazoles.

Prognostic value of metabolic syndrome in patients with heart failure and malnutrition.

BACKGROUND: Malnutrition is severely associated with worst prognosis of patients with heart failure (HF). Malnourished patients with the metabolic syndrome (MS) can result in a double burden of malnutrition. We aimed to investigate the impact of the MS on clinical outcomes in malnourished HF patients. METHODS: We examined 529 HF patients at risk of malnutrition with a mean age of (66 ± 10) years and 78% (415) were male. Nutritional status defined primarily by the prognostic nutritional index (PNI), with PNI < 40 being defined as malnutrition. The follow-up endpoint was cardiovascular death or all-cause death. RESULTS: During the 36-month follow-up, survival rates for cardiovascular and all-cause death were significantly lower in the MS group than in the non-MS group (log-rank P < 0.01). Multivariate Cox proportional hazards regression models showed that MS was independently associated with cardiovascular death (HR:1.759, 95%CI:1.351-2.291, p < 0.001) and all-cause death (HR:1.326, 95%CI:1.041-1.689, p = 0.022) in malnourished patients with HF. MS significantly increased the predictive value of cardiovascular death (AUC:0.669, 95%CI:0.623-0.715, p < 0.001) and all-cause death (AUC:0.636, 95%CI:0.585-0.687, p < 0.001) on the basis of established risk factors. The predictive effect of MS on cardiovascular death was independent of sex, age, functional class and left ventricular ejection fraction. CONCLUSIONS: In malnourished patients with HF, MS is an independent risk factor for cardiovascular and all-cause mortality. MS significantly enhance the predictive value for clinical events in patients.

Microwave photonics frequency measurement with improved accuracy based on an artificial neural network.

Photonics-assisted techniques for microwave frequency measurement (MFM) show great potential for overcoming electronic bottlenecks, with wild applications in radar and communication. The MFM system based on the stimulated Brillouin scattering (SBS) effect can measure the frequency of multiple high-frequency and wide-band signals. However, the accuracy of the MFM system in multi-tone frequency measurement is constrained by the SBS bandwidth and the nonlinearity of the system. To resolve this problem, a method based on an artificial neural network (ANN) is suggested, which can establish a nonlinear mapping between the measured two-tone signal spectra and the theoretical frequencies. Through simulation verification, the ANN optimized frequencies within the range of (0.5, 27) GHz of the MFM system show 79%, 76%, 70%, 44% reduction in errors separately under four spectral signal-to-noise ratios (SNR) conditions, 20 dB, 15 dB, 10 dB, 0 dB, and the frequency resolution is improved from 30 MHz to 10 MHz.

The role of evidence-based practice and empathy in shared decision-making attitudes among newly graduated nurses: A cross-sectional study.

AIM: Examine the levels of variables and explore drivers associated with shared decision-making attitudes among newly graduated nurses. DESIGN: This was a descriptive and cross-sectional study. METHODS: From August 2022 to October 2022, a cross-section of 216 newly graduated nurses from four comprehensive A-level hospitals in northern China was recruited using convenience sampling. Newly graduated nurses are generally defined as nurses with a service period of six months to one year. Data were collected using an online questionnaire support platform, including the Nursing Shared Decision-Making Attitude scale, Jefferson scale of Empathy-Health profession students and the Health Sciences Evidence-Based Practice questionnaire. All data were analysed descriptively, and correlational analysis and hierarchical regression were used to make identical connections between variables. RESULTS: Newly graduated nurses supported shared decision-making. Perceptions of shared decision-making were correlated with the experiences of empathy and evidence-based practice. Additionally, perspective-taking of empathy and beliefs, and the ability to search for and apply existing scientific findings of evidence-based practice had a significant impact on more positive attitudes. CONCLUSION: The survey showed that acceptance of shared decision-making was positive among newly graduated nurses. Clinical nursing managers and teachers should pay attention to cultivating the evidence-based practice and empathy of newly graduated nurses to adopt an optimistic attitude towards shared decision-making in the long term. IMPACT: The survey addresses attitudes of shared decision-making among newly graduated nurses and determines whether empathy and evidence-based practice has an impact on it. The main finding is that newly graduated nurses have an optimistic outlook on the implementation of shared decision-making. This survey showed that empathy and evidence-based practice competencies are associated with shared decision-making attitudes among newly graduated nurses. The results of this survey have an impact on educational institutions and hospitals in the form of recommendations. Several training programmes on empathy and evidence-based practice can help adopt the shared decision-making attitudes of newly graduated nurses. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Research on Over-the-Horizon Perception Distance Division of Optical Fiber Communication Based on Intelligent Roadways.

With the construction and application of more and more intelligent networking demonstration projects, a large number of advanced roadside digital infrastructures are deployed on both sides of the intelligent road. These devices sense the road situation in real time through algorithms and transmit it to edge computing units and cloud control platforms through high-speed optical fiber transmission networks. This article proposes a cloud edge terminal architecture system based on cloud edge cooperation, as well as a data exchange protocol for cloud control basic platforms. The over-the-horizon scene division and optical fiber network communication model are verified by deploying intelligent roadside devices on the intelligent highway. At the same time, this article uses the optical fiber network communication algorithm and ModelScope large model to model inference on real-time video data. The actual data results show that the StreamYOLO (Stream You Only Look Once) model can use the Streaming Perception method to detect and continuously track target vehicles in real-time videos. Finally, the method proposed in this article was experimentally validated in an actual smart highway digital infrastructure construction project. The experimental results demonstrate the high application value and promotion prospects of the fiber optic network in the division of over the horizon perception distance in intelligent roadways construction.

Histone modification: Biomarkers and potential therapies in colorectal cancer.

The complex mechanism of colorectal cancer development is closely associated with epigenetic modifications and is caused by overexpression and/or inactivation of oncogenes. Histone modifying enzymes catalyze histone modifications to alter gene expression, which plays a crucial role in the development and progression of colorectal cancer. Currently, there is more frequent study on histone acetylation, methylation, and phosphorylation, and their mechanisms in colorectal cancer development are clearer. This article elaborates on the role of histone modification in epigenetics in colorectal cancer development and discusses recent advances in using it as biomarkers and therapeutic targets for the treatment of colorectal cancer. The review aims to demonstrate the significant role of histone modification as a new therapeutic target in colorectal cancer and provides insights into the novel diagnostic and therapeutic options it offers.

Movement of protistan trophic groups in soil-plant continuums.

Protists, functionally divided into consumers, phototrophs, and parasites act as integral components and vital regulators of microbiomes in soil-plant continuums. However, the drivers of community structure, assembly mechanisms, co-occurrence patterns, and the associations with human pathogens and different protistan trophic groups remain unknown. Here, we characterized the phyllosphere and soil protistan communities associated with three vegetables under different fertilization treatments (none and organic fertilization) at five growth stages. In this study, consumers were the most diverse soil protist group, had the role of inter-kingdom connector, and were the primary biomarker for rhizosphere soils which were subjected to decreasing deterministic processes during plant growth. In contrast, phototrophs had the greatest niche breadth and formed soil protistan hubs, and were the primary biomarkers for both bulk soils and the phyllosphere. Parasites had minimal input to microbial co-occurrence networks. Organic fertilization increased the relative abundance (RA) of pathogenic protists and the number of pathogen-consumer connections in rhizosphere soils but decreased protistan richness and the number of internal protistan links. This study advances our understanding of the ecological roles and potential links between human pathogens and protistan trophic groups associated with soil-plant continuums, which is fundamental to the regulation of soil-plant microbiomes and maintenance of environmental and human health.

HER2-targeting antibody-drug conjugate RC48 alone or in combination with immunotherapy for locally advanced or metastatic urothelial carcinoma: a multicenter, real-world study.

BACKGROUND: Phase II trials showed the efficacy of anti-HER2 RC48-ADC (disitamab vedotin) for HER2-positive metastatic urothelial carcinoma (UC). This study evaluated RC48 alone verses in combination with immunotherapy for locally advanced or metastatic UC using real-world data. METHODS: This retrospective, multicenter, real-world study included patients with locally advanced or metastatic UC who received RC48 in five hospitals in China between July 2021 and April 2022. The outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events. RESULTS: Thirty-six patients were included. The patients were 47-87 years, and 26 (72.2%) were male. Eighteen patients received RC48 alone, and 18 received RC48 combined with a programmed death-1 antibody. The median PFS was 5.4 months. The median OS was not reached. The 6-month and 1-year PFS rates were 38.8% and 15.5%, respectively. The 1-year OS rate was 79.6%. Fourteen (38.9%) patients achieved a partial response, and the ORR was 38.9%. Eleven patients had stable disease, and the DCR was 69.4%. The median PFS for patients who received RC48 combined with immunotherapy and those who received RC48 alone was 8.5 and 5.4 months, respectively. The main treatment-related adverse events included anemia, hypoesthesia, fatigue, and elevated transaminase. No treatment-related death occurred. CONCLUSION: RC48 alone or combined with immunotherapy might benefit patients with locally advanced or metastatic UC, regardless of impaired renal function.

Effect of chemotherapy alone or combined with immunotherapy for locally advanced or metastatic genitourinary small cell carcinoma: a real-world retrospective study.

BACKGROUND: Genitourinary small cell carcinoma is rare, and has a poor prognosis. However, effective treatment options for this disease are limited. We present a study to assess the efficacy of chemotherapy alone or combined with immunotherapy for locally advanced or metastatic genitourinary small cell carcinoma (GSCC). METHODS: We performed a retrospective analysis of patients with locally advanced or metastatic GSCC from Jan 2013 to September 2022 at Sun Yat-sen University Cancer Center. The survival and safety profiles were analyzed. RESULTS: Forty-two GSCC patients were enrolled, which included 20 with chemotherapy plus immunotherapy and 22 with chemotherapy alone. The median follow-up time was 15.13 months (95% CI, 8.84-21.42). The addition of immunotherapy to chemotherapy demonstrated no significant difference in median progression-free survival (p = 0.37). However, the median overall survival (OS) was 22.97 and 14.03 months with immunotherapy plus chemotherapy and chemotherapy alone, respectively (HR = 0.69, 95%CI 0.08-0.55, p = 0.017). Two patients with immunotherapy plus chemotherapy achieved clinical complete remission. The overall response rate for patients receiving chemotherapy combined with immunotherapy was 65%, which was higher in comparison to those treated with chemotherapy alone (50%). Univariate and multivariate analyses demonstrated that chemotherapy combined with immunotherapy independently achieved favorable OS. Four patients experienced immunotherapy-related adverse events, with one developing grade 3 hypothyroidism. CONCLUSIONS: Among patients with locally advanced or metastatic GSCC, immunotherapy combined with chemotherapy might be thought of as a potentially effective treatment option for patients with GSCC.

First-line programmed death receptor-1 (PD-1) inhibitor and epidermal growth factor receptor (EGFR) blockade, combined with platinum-based chemotherapy, for stage IV penile cancer.

OBJECTIVES: To evaluate the anti-tumour activity and safety of anti-programmed death receptor-1 (PD-1) antibody plus epidermal growth factor receptor blockade combined with platinum-based chemotherapy (PEP) as first-line therapy for stage IV penile squamous cell carcinoma (PSCC). PATIENTS AND METHODS: We conducted a retrospective review of 17 patients with stage IV PSCC undergoing first-line PEP at Sun Yat-sen University Cancer Center between January 2018 and September 2021. Clinical responses were assessed using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Adverse events (AEs) were graded according to Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Of 17 patients who received first-line PEP, 13 were observed to have partial responses. Twelve patients subsequently received consolidated surgery. Nine of these achieved pN0 status, of whom six with locally advanced PSCC achieved pathological complete response. The median (range) follow-up time was 24.87 (3.63-29.40) months. Median PFS and median OS were not reached, with 2-year PFS and OS rates being 68.4% (95% confidence interval [CI] 48.7-96.1) and 62.9% (95% CI 41.6-95), respectively. Eight patients experienced Grade 3 or 4 treatment-related AEs. No Grade 5 AEs or death associated with treatment was observed. CONCLUSIONS: Anti-PD-1 antibody plus epidermal growth factor receptor blockade and platinum-based chemotherapy showed promising anti-tumour activity, acceptable toxicity, and satisfying long-term survival for stage IV PSCC. Larger clinical trials are needed to validate our findings.