Real-world retrospective study of immune checkpoint inhibitors in combination with radiotherapy or chemoradiotherapy as a bladder-sparing treatment strategy for muscle-invasive bladder urothelial cancer

BackgroundRecent developments in MIBC treatment suggest good efficacy of bladder sparing treatment combined with immune checkpoint inhibitor. However, there is no standard treatment mode. A retrospective analysis was conducted to reveal the efficacy and safety of PD-1 inhibitor in combination with radiotherapy or chemoradiotherapy.MethodsWe retrospectively analyzed 25 patients with MIBC T2-T3N0M0 disease who were unfit or unwilling to undergo RC. These patients underwent the maximum TURBT followed by PD-1 inhibitor (Tislelizumab or Toripalimab) in combination with radiotherapy or chemoradiotherapy (gemcitabine plus cisplatin) between April 2020 and May 2022. The primary outcome was clinical complete response (cCR) rate. The secondary outcomes were disease free survival (DFS) and overall survival (OS).ResultsRevised: Of 25 patients, 22 were T2 (88%), while 3 were T3 (12%). The median age is 65 years (51–80). Twenty-one patients had programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or more, and 4 patients had CPS<1 or unknown. Sixteen patients received chemoradiotherapy. Tislelizumab and Toripalimab were administered to 19 and 6 patients, respectively. The median number of cycles of immunotherapy was 8. Twenty-three patients (92%) achieved cCR. Following a median of 13 months of follow-up (range, 5-34 months), 1-year DFS and OS rate were 92% and 96%, respectively. In the univariate analysis, T stage significantly influenced OS and ORR, and efficacy evaluation significantly influenced OS, DFS, and ORR. The expression of PD-L1 and chemotherapy had no effect on prognosis. In the multivariate analysis, no independent prognostic factors were found. Grade 3 or 4 adverse events (AE) were reported in 35.7% patients.ConclusionsBladder sparing therapy with PD-1 inhibitor in combination with radiotherapy or chemoradiotherapy is feasible, safe, and highly effective for patients who were unfit or unwilling to undergo RC

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Synthesis and Study of Zinc Orotate and Its Synergistic Effect with Commercial Stabilizers for Stabilizing Poly(Vinyl Chloride)

Synthesis and Study of Zinc Orotate and Its Synergistic Effect with Commercial Stabilizers for Stabilizing Poly(Vinyl Chloride

Neoadjuvant chemotherapy plus surgery versus concurrent chemoradiotherapy in stage IB2-IIB cervical cancer: A systematic review and meta-analysis.

The optimal treatment strategy for stage IB2-IIB cervical cancer is controversial. This systematic review with meta-analysis evaluated the efficacy of concomitant chemoradiotherapy (CCRT) and neoadjuvant chemotherapy followed by radical surgery (NACT+S). Studies that evaluated NACT+S versus CCRT for patients with Federation of Gynecology and Obstetrics stage IB2-IIB cervical cancer were searched in MEDLINE, EMBASE, and the Cochrane Library database. Hazard ratios (HRs) with their respective 95% confidence intervals (CIs) were calculated using a random-effects model. Toxicity was also evaluated. Six qualified retrospective studies and one randomized controlled trial (2270 patients) were included in this review. The results suggested that compared with CCRT, NACT+S did not improve overall survival in all patients (HR 0.73, 95% CI 0.52-1.02) or stage IIB patients (HR 0.83, 95% CI 0.61-1.15). NACT+S did not improve disease-free survival (DFS) in stage IIB patients (HR 1.10, 95% CI 0.70-1.71). In the analysis of DFS in all patients, a high degree of heterogeneity was detected (I2 = 84%). Sensitivity analysis that eliminated these heterogeneous data suggested that CCRT could improve DFS over NACT+S (HR 1.47, 95% CI 1.12-1.93). Diarrhea and rectal and bladder complications occurred at a lower rate in the NACT+S group than in the CCRT group. NACT+S had no survival advantage for patients with stage IB2-IIB cervical cancer compared with CCRT but was associated with fewer side effects. Further prospective studies with a larger sample size of treatment protocols for locally advanced cervical cancer are needed

Propensity score matching analysis to comparing cisplatin versus nedaplatin based doublet agent concurrent chemoradiotherapy for locally advanced cervical cancer

Abstract This study evaluated the efficacy and safety of cisplatin and nedaplatin in three-week doublet agent concurrent chemoradiotherapy (CCRT) for patients with locally advanced cervical cancer (LACC). We retrospectively enrolled patients with stage IIB-IIIC2 cervical cancer who received doublet agent CCRT from January 2015 to December 2020. Clinical outcomes were analyzed using the Kaplan–Meier method and a Cox proportional hazards model. Propensity score (PS) matching analysis was used to compare cisplatin plus docetaxel group and nedaplatin plus docetaxel group. A total of 295 patients were included. The 5-year overall survival rate (OS) and progression free survival rate (PFS) were 82.5% and 80.4%, respectively. After PS matching, there were 83 patients each in the nedaplatin group and cisplatin group. There were no significant differences in objective response rates (97.6% and 98.8%, p = 0.212), 5-year OS rate (96.5 vs 69.8, p = 0.066), PFS rate (90.8 vs 72.4, p = 0.166), and toxicity between the two groups. Doublet agent concurrent chemoradiotherapy is feasible, safe, and shows high efficacy in LACC patients. Here, cisplatin group has a trend of better prognosis, suggesting that cisplatin is preferred and nedaplatin can be considered for replacement when cisplatin is intolerant

Development and Investigation of Lanthanum Sulfadiazine with Calcium Stearate and Epoxidised Soyabean Oil as Complex Thermal Stabilizers for Stabilizing Poly(vinyl chloride)

Development and Investigation of Lanthanum Sulfadiazine with Calcium Stearate and Epoxidised Soyabean Oil as Complex Thermal Stabilizers for Stabilizing Poly(vinyl chloride

SOX9/miR-130a/CTR1 axis modulates DDP-resistance of cervical cancer cell

<p>Cisplatin (DDP) -based chemotherapy is a standard strategy for cervical cancer, while chemoresistance remains a huge challenge. Copper transporter protein 1 (CTR1), a copper influx transporter required for high affinity copper (probably reduced Cu I) transport into the cell, reportedly promotes a significant fraction of DDP internalization in tumor cells. In the present study, we evaluated the function of CTR1 in the cell proliferation of cervical cancer upon DDP treatment. MicroRNAs (miRNAs) have been regarded as essential regulators of cell proliferation, apoptosis, migration, as well as chemoresistance. By using online tools, we screened for candidate miRNAs potentially regulate CTR1, among which miR-130a has been proved to promote cervical cancer cell proliferation through targeting PTEN in our previous study. In the present study, we investigated the role of miR-130a in cervical cancer chemoresistance to DDP, and confirmed the binding of miR-130a to CTR1. SOX9 also reportedly act on cancer chemoresistance. In the present study, we revealed that SOX9 inversely regulated miR-130a through direct targeting the promoter of miR-130a. Consistent with previous studies, SOX9 could affect cervical cancer chemoresistance to DDP. Taken together, we demonstrated a SOX9/miR-130a/CTR1 axis which modulated the chemoresistance of cervical cancer cell to DDP, and provided promising targets for dealing with the chemoresistance of cervical cancer.</p