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Introduction: Lenvatinib is indicated for the forefront treatment of advanced hepatocellular carcinoma (aHCC), but its use may be limited by the risk of esophagogastric varices (EGV) bleeding. This study assessed the prevalence, predictors, and complications of EGV in aHCC patients treated with lenvatinib. Methods: In this multicenter international retrospective study, cirrhotic patients treated with lenvatinib for aHCC, were enrolled if upper-gastrointestinal endoscopy was available within 6 months before treatment. Primary endpoint was the incidence of EGV bleeding during lenvatinib therapy; secondary endpoints were predictors for EGV bleeding, prevalence, and risk factors for the presence of EGV and high-risk EGV at baseline, as well as impact of EGV bleeding on patients' survival. Results: 535 patients were enrolled in the study (median age: 72 years, 78% male, 63% viral etiology, 89% Child-Pugh A, 16% neoplastic portal vein thrombosis [nPVT], 56% Barcelona Clinic Liver Cancer-C): 234 had EGV (44%), 70 (30%) were at high risk and 59 were on primary prophylaxis. During lenvatinib treatment, 17 patients bled from EGV (3 grade 5), the 12-month cumulative incidence being 3%. The only baseline independent predictor of EGV bleeding was the presence of baseline high-risk EGV (hazard ratio: 6.94, 95% confidence interval [CI]: 2.23-21.57, p = 0.001). In these patients the 12-month risk was 17%. High-risk varices were independently associated with Child-Pugh B score (odds ratio [OR]: 2.12; 95% CI: 1.08-4.17, p = 0.03), nPVT (OR: 2.54; 95% CI: 1.40-4.61, p = 0.002), and platelets <150,000/µL (OR: 2.47; 95% CI: 1.35-4.50, p = 0.003). Conclusion: In hepatocellular carcinoma patients treated with lenvatinib, the risk of EGV bleeding was mostly low but significant only in patients with high-risk EGV at baseline.
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BACKGROUND: Unintended secondary changes in the posterior tibial slope (PTS) and tibial torsion angle (TTA) may occur after medial open-wedge high tibial osteotomy (MOWHTO). In surgical procedures using patient-specific instruments (PSIs), it is essential to reproduce the PTS and TTA that were planned in simulations. PURPOSE: To analyze the factors causing unintended sagittal and axial alignment changes after MOWHTO. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Overall, 63 patients (70 knees) who underwent MOWHTO using a PSI between June 2020 and June 2023 were retrospectively reviewed. Preoperative and postoperative computed tomography scans were 3-dimensionally reconstructed. Simulated osteotomy was performed so that the weightbearing line could pass through the target point. A PSI gapper was 3-dimensionally printed to fit the posteromedial corner of the osteotomy gap in the simulated HTO model. After MOWHTO using the PSI gapper, the actual postoperative model was compared with the preoperative or simulation model. This assessment included PTS, TTA, hinge axis, and osteotomy-related parameters. Cortical breakage around the lateral hinge was evaluated to assess stability. RESULTS: The mean PTS and TTA did not change in the simulation. However, significant changes were observed in the actual postoperative PTS and TTA (change, -2.4°± 2.2° and -3.9°± 4.7°, respectively). The PTS was reduced, while the TTA decreased with internal rotation of the distal fragment. The difference in the axial hinge axis angle (AHA) between the simulation and actual surgery was the factor most correlated with the difference in the PTS (r = 0.625; P < .001). In regression analysis, the difference in the AHA was the only factor associated with the difference in the PTS (ß = 0.558; P = .001), and there were no factors that showed any significant associations with the difference in the TTA. In subgroup analyses for the change in the TTA, the correction angle and anterior osteotomy angle were significantly higher in the more internal rotation group (P = .023 and P = .010, respectively). The TTA change was significantly higher in the unstable group with lateral cortical breakage (P = .018). The unstable group was more likely to show an internal rotation of ≥5° (odds ratio, 5.0; P = .007). CONCLUSION: The AHA was associated with a difference in the PTS between the simulation and actual surgery. The change in the TTA was caused by a combination of multiple factors, such as a large correction angle and anterior osteotomy angle, but mainly by instability of the lateral cortical hinge.
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Imageamento Tridimensional , Osteotomia , Tíbia , Tomografia Computadorizada por Raios X , Humanos , Osteotomia/métodos , Tíbia/cirurgia , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Adulto , Osteoartrite do Joelho/cirurgiaRESUMO
PURPOSE: Exon 20 insertion mutations (E20ins) in epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER2) in non-small cell lung cancer (NSCLC) patients has become more important with emergence of novel agents targeting E20ins. MATERIALS AND METHODS: Advanced/Metastatic NSCLC patients with E20ins were included. EGFR E20ins was identified by two methods, next-generation sequencing (NGS) or real-time polymerase chain reaction (PCR), while HER2 E20ins was done by NGS only. RESULTS: Between December 2013 and July 2021, E20ins were identified in 107 patients at Asan Medical Center; 67 EGFR E20ins and 40 HER2 E20ins. Out of 32 patients with EGFR E20ins who had tested both PCR and NGS, 17 were identified only through NGS and the other 15 through both tests, giving a discordance rate of 53.1%. There was no clinically significant difference in clinicopathologic features between EGFR and HER2 E20ins; both were observed more frequently in adenocarcinoma, female and never-smokers. Brain metastases were evident at diagnosis in 31.8% of EGFR E20ins and 27.5% of HER2 E20ins, respectively. Platinum-based doublets demonstrated objective response rates (ORR) of 13.3% with a median progression-free survival (PFS) of 4.2 months for EGFR E20ins and 35.3% with 4.7 months for HER2 E20ins, respectively. In contrast, novel EGFR E20ins-targeted agents exhibited an ORR of 46.2% with a median PFS of 5.4 months, while HER2-targeted agents showed an ORR of 50% with that of 7.0 months. CONCLUSION: Identification of EGFR and HER2 E20ins is more important as their targeted therapies improved outcomes. Upfront NGS test as a comprehensive molecular approach is strongly warranted.
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Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Éxons , Neoplasias Pulmonares , Receptor ErbB-2 , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Receptores ErbB/genética , Feminino , Masculino , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Pessoa de Meia-Idade , Idoso , Adulto , Mutagênese Insercional , Resultado do Tratamento , Idoso de 80 Anos ou mais , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
BACKGROUND: The transition of human epidermal growth factor receptor 2 (HER2) status after neoadjuvant chemotherapy (NAC) in HER2-low breast cancer has not been thoroughly evaluated. Here, we evaluated the HER2 transition among HER2-zero and HER2-low breast cancer cases post-NAC and its impact on clinical outcomes. METHODS: We included 1288 patients with HER2-low or zero breast cancer who underwent NAC and surgery between 2014 and 2018 and had paired pre- and post-therapeutic HER2 status results. RESULTS: Among patients who were HER2-zero pre-NAC (n = 650), 68% and 29% were HER2-zero and HER2-low, respectively, post-NAC. Among patients who were HER2-low pre-NAC (n = 638), 32% of patients showed HER2 changes (low to zero), and 59% of patients had a constant HER2-low status post-NAC. Patients with constant HER2-low or transitions from HER2-low to zero had a higher proportion of hormone receptor positivity (84% and 79%) than those with changes from HER2-zero to low (77%) or with constant HER2-zero (56%), respectively. Multivariable logistic regression analysis revealed that patients with oestrogen receptor positivity had a higher probability of gaining HER2-low expression than those with oestrogen receptor negativity (odds ratio 2.48). No significant differences were observed in terms of overall survival or disease-free survival between patients with and without HER2-changes according to their hormone receptor status, except in the post-therapeutic HER2-low, hormone receptor-negativity subset. CONCLUSION: Temporal heterogeneity of HER2-low expression is observed in substantial numbers of post-NAC breast cancer patients. Clinical outcomes show no significant associations, except in the post-therapeutic HER2-low, hormone receptor negativity subset. The prognostic implications of HER2 transition in HER2-low breast cancer require further investigation.
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Neoplasias da Mama , Humanos , Feminino , Prognóstico , Receptores de Estrogênio/metabolismo , Terapia Neoadjuvante , Receptor ErbB-2/metabolismo , Intervalo Livre de Doença , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia AdjuvanteRESUMO
PURPOSE: The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population. Materials and Methods: This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status. RESULTS: Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]). CONCLUSION: Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante , Estudos Retrospectivos , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/cirurgia , Quimioterapia Adjuvante , Neoplasias PancreáticasRESUMO
Background: Adjuvant chemotherapy is the standard treatment after curative-intent surgery for pancreatic ductal adenocarcinoma (PDAC). The phase-3 ESPAC-4 trial demonstrated significantly improved overall survival (OS) with Gemcitabine plus capecitabine (GemCap) over Gemcitabine (Gem) in Europe. We conducted a retrospective efficacy and safety evaluation of GemCap versus Gem in an Asian population. Methods: This retrospective analysis included 292 patients with PDAC who received adjuvant Gem or GemCap after curative resection between January 2017 and December 2020 at Asan Medical Center, Seoul, Korea. Results: Adjuvant Gem and GemCap were administered to 161 (55.1%) and 131 (44.8%) patients, respectively. The Gem group had significantly older patients (median 66 versus 63 years, p = 0.001); otherwise, the groups had similar baseline characteristics. With median follow-up durations of 39.4 [95% confidence interval (CI), 36.9-45.0] and 39.4 (95% CI, 34.7-41.6) months in the Gem and GemCap groups, the median OS was 36.8 (95% CI, 29.7-43.5) and 46.1 (95% CI, 31.5-not reached) months in the Gem and GemCap groups, respectively [unadjusted hazard ratio (HR) = 0.7; 95% CI, 0.5-1.0; p = 0.07). The median recurrence-free survival was 14.3 (95% CI, 12.9-17.7) and 17.0 (95% CI, 13.3-28.2) months, respectively (p = 0.5). Hand-foot skin reactions (any grade, 15.3% versus 0.6%; p < 0.001), neutropenia (78.6% versus 67.7%, p = 0.04) and thrombocytopenia (30.5% versus 20.5%, p = 0.04) were more common in the GemCap group. Multivariate analysis revealed adjuvant GemCap - compared with Gem - to be significantly associated with better OS (adjusted HR = 0.6; 95% CI, 0.4-0.9; p = 0.01). Otherwise, moderate or poor histological grade, lymph node positivity, positive resection margin, and elevated CA 19-9 (>median) were significantly associated with worse OS. Conclusions: Adjuvant GemCap showed the consistent clinical outcomes with the ESPAC-4 trial. As mFOLFIRINOX is the new standard treatment for medically fit patients with resected PDAC, further evaluation of optimal adjuvant chemotherapy in daily practice is warranted.