Current Issue : April-June Volume : 2025 Issue Number : 2 Articles : 5 Articles
Osteosarcoma is the most common form of primary bone cancer, which primarily afflicts children and adolescents. Chemotherapy, consisting of doxorubicin, cisplatin and methotrexate (MAP) increased the 5-year osteosarcoma survival rate from 20% to approximately 60% by the 1980s. However, osteosarcoma survival rates have remained stagnant for several decades. Patients whose disease fails to respond to MAP receive second-line treatments such as etoposide and, in more recent years, the kinase inhibitor regorafenib. BCL-2 and its close relatives enforce cellular survival and have been implicated in the development and progression of various cancer types. BH3- mimetics antagonize pro-survival members of the BCL-2 family to directly stimulate apoptosis. These drugs have been proven to be efficacious in other cancer types, but their use in osteosarcoma has been relatively unexplored to date. We investigated the potential efficacy of BH3-mimetics against osteosarcoma cells in vitro and examined their cooperation with regorafenib in vivo. We demonstrated that osteosarcoma cell lines could be killed through inhibition of MCL-1 combined with BCL-2 or BCL-xL antagonism. Inhibition of MCL-1 also sensitized osteosarcoma cells to killing by second-line osteosarcoma treatments, particularly regorafenib. Importantly, we found that inhibition of MCL-1 with the BH3-mimetic S63845 combined with regorafenib significantly prolonged the survival of mice bearing pulmonary osteosarcoma metastases. Together, our results highlight the importance of MCL-1 in osteosarcoma cell survival and present a potential therapeutic avenue that may improve metastatic osteosarcoma patient outcomes....
Background and Objectives: Neoadjuvant chemotherapy (NAC) improves survival by increasing pathologic complete response (pCR). Blood-based indexes have been studied in breast cancer for predicting pCR and prognosis, but the results are conflicting. We aimed to assess the impact of inflammatory and nutritional indexes on pCR and survival. Materials and Methods: We retrospectively analyzed 304 patients. Pre-NAC laboratory data were used to calculate their neutrophil-tolymphocyte ratios (NLR), pan-immune inflammation values (PIV), lactate dehydrogenase–albumin ratios (LAR), and prognostic nutritional indexes. The optimal cut-off values were determined through an analysis of the receiver operating characteristic curve. Survival analyses were performed using the Kaplan–Meier method. Multivariate regression analyses were performed to reveal the factors predicting pCR. Univariate and multivariate survival analyses were conducted to identify prognostic factors predicting survival. Results: The median follow-up was 38.5 months. pCR was achieved in 41.4% of the patients. In the univariate analyses, the NLR (p = 0.032) and PIV (p = 0.002) were indexes associated with pCR. In the multivariate analysis, the PIV (p = 0.008) was the only index significantly correlated with pCR. According to the multivariate Cox regression analyses, clinical stage 3 (p = 0.032), a pathologic response other than pCR (p = 0.021), and a high LAR (≥4.72) (p = 0.002) were correlated with increased recurrence risk. The univariate Cox regression analyses revealed that failure to achieve pCR (p = 0.037) and the presence of a high LAR (p = 0.044) were significant predictors of overall survival. However, the multivariate analyses failed to identify any significant predictors of death. Conclusions: We found that the PIV was more effective than the other indexes in predicting pCR. To our knowledge, this study is the first to determine an association between the LAR and disease-free survival in patients with breast cancer receiving NAC.We concluded that a high LAR was a poor prognostic factor, especially in patients without a pCR. Therefore, close postoperative monitoring and the intensification of adjuvant treatment should be considered for these patients. However, further studies are needed to confirm our findings....
Objectives: Muscle-invasive bladder cancer (MIBC) has a poor prognosis with a 5-year overall survival rate of 50%. Current guidelines recommend the use of neoadjuvant chemotherapy (NAC) followed by radical cystectomy in these patients. However, its application remains limited and underutilized in clinical practice. This study aims to delineate, in real-life practice, the clinical characteristics and outcomes of patients with muscle-invasive bladder cancer (MIBC) who received NAC and were subsequently candidates for cystectomy. Methods: This study is a retrospective observational analysis of patients with muscle- invasive bladder cancer (stages T2-T4aN0M0 and T1-T4aN1M0) who received neoadjuvant chemotherapy prior to total cystectomy. The data, collected over a six-year period from 2018 to 2024, originates from Hotel Dieu de France University Hospital in Beirut. Various factors were analyzed, including age, sex, history of smoking, stage of disease at diagnosis, presence of carcinoma in situ (CIS), and any prior history of Bacillus Calmette-Guérin (BCG) treatment or T1 or Ta disease. Additionally, the study evaluates renal function prior to neoadjuvant chemotherapy (NAC), specifies the type and number of chemotherapy cycles administered, the pathological complete response (pCR) following cystectomy and calculate both overall survival and disease-free survival rates. Results: A total of 36 patients were analyzed, with a median age of 71.6 years. 77.7% were male, 22.2% were female, and 77.8% were smokers. 55.6% of the patients presented with de novo muscle-invasive bladder cancer (MIBC), 44.4% had a history of Ta or T1 stage tumors and 100% had urothelial histology and lower tract location. Among these 36 patients, 27.8% had received intravesical Bacillus Calmette-Guérin (BCG) treatment, while 72.2% did not. 86.1% of patients had a creatinine clearance greater than 60, whereas 13.9% had a clearance below 60 but still above 50. At the time of diagnosis, 61.1% were at stage II, 13.9% were at stage IIIa, and 25.0% were at stage IIIb. All the patients received the combination of gemcitabine and cisplatin with a median number of 3.9 cycles per patient. Out of the 36 patients, 5 experienced disease progression and did not undergo radical cystectomy, while another 5 opted for trimodal therapy (TMT) after evaluation by cystoscopy showing no residual lesion. The remaining 26 patients proceeded with radical cystectomy. Among these 26 cystectomized, 30.8% demonstrated a complete pathological response. During the follow-up period, 75% of these 36 patients did not experience disease progression, with a median disease-free survival of 9.5 months and a mean disease-free survival of 19.72 months. No deaths were recorded in this study, and overall survival data could not be determined. Conclusion: In our real-world experience, approximately one-third of patients who received gemcitabine and cisplatin NAC followed by radical cystectomy achieved a pathological complete response. Extended follow-up is necessary to assess longterm outcomes, including median overall survival. Future research should focus on investigating and comparing between triple modality therapy and cystectomy, both after neoadjuvant chemotherapy....
Hepatitis delta virus (HDV) infection requires the presence of hepatitis B virus (HBV), and chronic HBV–HDV coinfection is considered the most severe form of viral hepatitis. When compared with HBV mono-infection, HBV–HDV coinfection is associated with higher rates of liver cirrhosis and hepatocellular carcinoma (HCC). In this review, we aim to elucidate the complex relationship between HDV infection and the development of HCC. The exact mechanisms underlying the carcinogenic potential of HDV remain to be fully elucidated. Evidence suggests that HDV has both indirect and direct oncogenic effects. Indirect effects promote accelerated progression to liver cirrhosis, which results in a different tumor microenvironment. Direct oncogenic effects are suggested by a distinct molecular signature. The recent epidemiological data regarding HBV–HDV coinfection should make us reconsider the HCC screening strategy, with special focus in younger non-cirrhotic patients. Finally, treating HCC in patients with chronic HDV poses unique challenges due to the complex interplay between HBV and HDV and the severity of liver disease. An in-depth understanding of the epidemiology and pathophysiology of HDV infection and carcinogenesis is essential to improve disease management in this high-risk population....
Purpose It is controversial for the optimal time of breast cancer surgery after COVID-19 infection. Purpose was to assess the risk of postoperative complication in breast cancer patients with COVID-19 infection, in order to select optimal surgery timing after COVID-19 infection. Methods Breast cancer patients infected with COVID-19 and performed surgery between December 20th, 2022 to March 20th, 2023 were included in this prospective study (n = 577). Patients performed surgery between May 1, 2019 to October 1, 2019 were listed as control group (n = 329). They had not been infected with COVID-19 before surgery. Patients were grouped by time of surgery relative to COVID-19 infection. Database was evaluated using logistic regression. Results Patients infected with COVID-19 had a higher incidence of complications after surgery compared to that not-COVID-19 infection (6.59% vs. 3.04%). Multivariable logistic analysis demonstrated that timing of surgery was associated with complications (OR = 4.253; 95% CI: 0.855–21.153, P = 0.044). Patients performed surgery within 2 weeks after COVID-19 infection had the highest rates of complication (17.65%) when compared with other groups, while the incidence was decreased into 5.51% when surgery 2 weeks or more after COVID-19 infection. With a median follow-up was 10 months, all patients with complications were recovered without serious complications or death, which had no adverse effect on subsequent anti-tumor therapy. Conclusions It needs to be cautious when breast cancer surgery was performed within 2 weeks after COVID- 19 infection. Although the incidence of complications in patients undergoing surgery 2 weeks after COVID-19 infection is still slightly high, surgery might be recommended considering urgency of treatment, good prognosis of complications and the lack of influence on subsequent adjuvant therapy....
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