Background
Coronavirus disease 2019 (COVID-19) has quickly turned into a global pandemic with close to 5 million cases and more than 320,000 deaths. Cancer patients constitute a group that is ...expected to be at risk and poor prognosis in COVID pandemic. We aimed to investigate how cancer patients are affected by COVID-19 infection, its clinical course and the factors affecting mortality.
Methods
In our single-center retrospective study, we included cancer patients with laboratory confirmed COVID-19 in our hospital. Demographic, clinical, treatment, and laboratory data were obtained from electronic medical records. Logistic regression methods were used to investigate risk factors associated with in-hospital death.
Results
In the hospital, 4489 patients were hospitalized with COVID infection and 77 were cancer patients. The mean age of cancer patients was 61.9 ± 10.9 and 44 of them were male (62%). While the mortality rate in non-cancer patients was 1.51% (
n
= 68), this rate was significantly higher in cancer patients, 23.9% (
n
= 17). The stage of the disease, receiving chemotherapy in the last 30 days also lymphopenia, elevated troponin I,
d
-dimer, CRP, and CT findings were associated with severe disease and mortality. Severe lung involvement (OR = 22.9,
p
= 0.01) and lymphopenia (OR = 0.99,
p
= 0.04) are the most important factors influencing survival in logistic regression.
Conclusions
The disease is more severe in cancer patients and mortality is significantly higher than non-cancer patients. These data show that it may be beneficial to develop dynamic prevention, early diagnosis and treatment strategies for this vulnerable group of patients who are affected by the infection so much.
Due to their primary effects on DNA synthesis, antimetabolites are most effective against actively dividing cells and are significantly specific to the cell cycle phase. Pralatrexate (PDX), an ...antifolate metabolite designed to accumulate in cancer cells, was the first new agent approved by the US Food and Drug Administration for the treatment of resistant/recurrent peripheral T-cell lymphomas. PDX was a drug that is frequently used not only for PTCL, but also for cutaneous T-cell lymphoma (CTCL), extranodal natural killer (NK) / T-cell lymphoma.
This article reviews Pralatrexate's history, pharmacokinetics, clinical phase studies including phases I, II and III, types of cancers it is effective on, drug side effects, inhibition mechanism and even its use in the treatment of other cancers with innovative methods, including its antiviral effect against SARS-CoV-2 infection.
A comprehensive internet-based research was planned, covering all published and unpublished studies on the subject. We conducted this review in accordance with Preferred Reporting Items for systematic reviews and metaanalysis (PRISMA-P), and Cochrane Collaboration reporting items for systematic reviews and meta-analysis. The results of the studies in the articles were recorded to include all phase studies.
Pralatrexate was structurally designed to have enhanced cellular transport via RFC (reduced folate carrier type) and be subject to more polyglutamation compared to methotrexate. The enhanced polyglutamylation ability of pralatrexate is associated with increased tumor cell death and ultimately improved anticancer activity. Pralatrexate is considered a promising drug for patients with recurrent and treatment-resistant PTCL with a good survival advantage. At the same time, it is an antifolate agent with a significant advantage over methotrexate as it does not cause myelosuppression.
While there are manageable side effects such as thrombocytopenia, neutropenia, and mucositis, it is critical to explore new approaches, targeted agents, novel cellular therapies, and immunotherapies to determine optimal pretreatment in the rare but heterogeneous disease PTCL, and future studies and experienced haematologists are needed.
Background
Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response ...rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab.
Patients and methods
In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (
p
< 0.1), and then included a final model of
p
< 0.05.
Results
The median follow-up duration was 23.5 months. Of the patients, 98 (86.7%) were male and 13.3% were female. The median age was 65 years of age (37–86). In univariate analysis, primary tumor location in the upper tract, increasing absolute neutrophil count (ANC), increasing absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR) > 3, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673–5.761;
p
< (0.001), ECOG PS (1 ≥) HR 2.184; 95% CI 1.120–4.256;
p
= 0.022, and Hemoglobin level below 10 mg/dl HR 2.680; 95% CI 1.558–4.608;
p
< (0.001). In addition, NLR > 3 hazard ratio HR 2.092; 95% CI 1.031–4.243;
p
= 0.041 and GFR less than 60 ml/min HR 1.829; 95% CI 1.1–3.041;
p
= 0.02, maintained a significant association with OS in multivariate analysis.
Conclusions
This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60 ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer.
Background
Atezolizumab (ATZ) has demonstrated antitumor activity in previous studies in patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of ATZ was ...modest. Therefore, finding biologic or clinical biomarkers that could help to select patients who respond to the immune checkpoint blockade remains important.
Patients and methods
In this study, we present the retrospective analysis of 105 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of patients were obtained from patient files and hospital records. The association between response to first-line chemotherapy and ATZ was using Fisher’s exact test. Median follow-up was calculated using the reverse Kaplan–Meier method. OS was estimated by using the Kaplan–Meier method.
Results
The median follow-up time was 23.5 months. Forty (74.1%) of patients who experienced clinical benefit after firs-line chemotherapy also had clinical benefit after atezolizumab, while only 14 (25.9%) of patients with initial PD after first-line chemotherapy subsequently experienced clinical benefit with ATZ (
p
= 0.001). The median OS on ATZ of 14.8 and 3.4 months for patients with clinical benefit and progressive disease in response to first-line chemotherapy, respectively (
p
= 0.001). Three of the adverse prognostic factors according to the Bellmunt criteria were independent factors of short survival: liver metastases {Hazard ratio HR = 1.9;
p
= 0.04}, ECOG PS ≥ 1 (HR = 2.7;
p
= 0.001), and Hemoglobin level below 10 mg/dl (HR = 2.8;
p
< 0.001). In addition, patients with clinical benefit from first-line chemotherapy (HR = 0.39;
p
< 0.001) maintained a significant association with OS in multivariate analysis.
Conclusions
Our study demonstrated that clinical benefit from first-line chemotherapy was independent prognostic factors on OS in patients’ use of ATZ as second-line treatment in metastatic bladder cancer. Furthermore, these findings are important for stratification factors for future immunotherapy study design in patients with bladder cancer who have progressed after first-line chemotherapy.
PURPOSE Durable complete response rates for metastatic renal cell carcinoma (mRCC) and metastatic bladder cancer (mBC) are low despite new therapy. Palliative care focuses on life extension and ...quality of life (QoL), not cure. This study aims to investigate patients' perceptions of treatment outcomes in mRCC and mBC and to assess the influence of QoL and optimism levels on these perceptions. METHODS From March 15, 2023, to January 15, 2024, a multicenter, cross-sectional online survey was carried out, targeting patients diagnosed with mRCC and mBC. The survey comprised structured questions aimed at evaluating perceptions concerning disease cure, symptom improvement, daily activity performance, and life extension due to treatment. Additionally, to evaluate optimism and QoL, the European Organization for Research and Treatment of Cancer 30.3 QoL questionnaire and life orientation test were implemented. Study on patients' perceptions of treatment outcomes in metastatic kidney and bladder cancer shows high optimism, inaccurate cure beliefs. RESULTS In total, 169 patients participated in the survey; the majority of the patients stated their general health status as good (72.2%) and excellent (13.6%). Patients who rated their overall health status as good-excellent had a higher median general QoL and optimism score compared with those who rated it as fair-poor. In all, 85.2% of patients considered the possibility of a cure very likely or likely. Most participants believed treatment could provide symptom relief (30.2% very likely, 49.1% likely), enhanced ability to perform daily activities (28.4% very likely, 55.6% likely), and life extension (32.5% very likely, 53.3% likely). Patients responding very likely and likely to these questions regarding treatment outcomes had higher QoL and optimism scores than those responding a little likely and not possible. CONCLUSION The majority of patients with mRCC and mBC held inaccurate beliefs about treatment outcomes. Better QoL and optimism were associated with increased inaccuracy.
Abstract
This study aims to investigate the prognostic value of the systemic immune-inflammation index (SII)and its impact on survival in patients with metastatic renal cell carcinoma (mRCC). A total ...of 706patients with mRCC treated with tyrosine kinase inhibitors (TKIs)between January 2007 and June 2020 (i.e., sunitinib, pazopanib) were included in this study. SII was calculated in 621 patients with the following formula:neutrophil (cellsx10
9
/L) x platelet (cellsx10
9
/L) / lymphocyte (cellsx10
9
/L).All patients were classified into SII-high and SII-low groups based on the cut-off value of SII at 756, which was the median SII level of our study group. The minimal follow-up duration was 10 months in all cohorts. The median age of patients was 60 (interquartile range (IQR):53–67) years. Three out of four patients were male. The majority of patients (85.7%) had clear cell histology, and sarcomatoid differentiation was observed in 16.9% of all patients. There were 311 and 310 patients in the SII-low and SII-high groups, respectively. In general, baseline characteristics were similar in each group. However, the rate of patients treated with sunitinib (63.3% vs. 49.0%,
p
< 0.001) and those who underwent nephrectomy (83.6% vs. 64.2%,
p
< 0.001) was higher in the SII-low group than in the SII-high group. On the other hand, patients with the IMDC poorrisk (31.6% vs. 8.0%,
p
< 0.001), those with bone (51.8% vs. 32.2%,
p
< 0.001) or central nervous system (12.9% vs. 5.8%,
p
= 0.026) metastasis, and those with Eastern Cooperative Oncology Group(ECOG) 2–4 performance score (28.1% vs.17.7%,
p
= 0.002) were more common in the SII-high group than in the SII-low group. The median overall survival (OS) was longer in the SII-low group than in the SII-high group (34.6 months vs. 14.5 months,
p
< 0.001). Similarly, the median progression-free survival (PFS) was longer in the SII-low group than in the SII-high group (18.0 months vs. 7.7 months,
p
< 0.001).In multivariableanalysis, SII was an independent prognostic factor for OS (hazard ratio (HR):1.39, 95% confidence interval (CI):1.05–1.85,
p
= 0.01) and PFS (HR:1.60, 95% CI:1.24–2.05,
p
< 0.001).Pre-treatment level of high SII might be considered a predictor of poor prognosisin patients with mRCC treated with TKIs.
Introduction
Clear cell renal cell carcinoma is characterized by mutation or inactivation of Von Hippel-Lindau suppressor gene. The mutation of Von Hippel-Lindau mechanism is associated with the ...upregulation of the hypoxia-inducible factor protein, inducing the overexpression of proteins including erythropoietin and vascular endothelial growth factor. Vascular endothelial growth factor receptor-targeted tyrosine kinase inhibitors are widely used in treatment of metastatic renal cell carcinoma. In paradoxical hematological effect with tyrosine kinase inhibitor therapies, hemoglobin level may be increased, but polycythemia requiring phlebotomy is very rare.
Case description
We present here a case of renal cell carcinoma who received successive treatment with sunitinib, everolimus, and axitinib. While he had a normal hemoglobin level with prior sunitinib treatment, on the sixth week of axitinib treatment, he developed polycythemia and treatment response was seen after axitinib-associated polycythemia.
Conclusion
Progression-free survival (PFS) was 30 months in our case with third-line treatment axitinib. Higher hemoglobin levels may be associated with longer survival. Polycythemia was the first response to treatment of axitinib in our patient. It may be an indicator of persistent treatment response.
Aim:The purpose of this study was to investigate the prognostic role of pretreatment Prognostic Nutritional Index (PNI) in metastatic renal cell carcinoma (mRCC) patients given pazopanib or sunitinib ...as first-line targeted therapy.Materials and Methods:We retrospectively analyzed the treatment modalities, demographic, clinical, and pathological features of 77 patients with mRCC, and calculated prognostic nutritional index. Based on the median value, patients were grouped as those having low and high PNI values. The Kaplan-Meier method was used for survival analysis, and Cox-regression analysis was used for univariate and multivariate analyses.Results:The overall median progression-free survival (PFS) and overall survival (OS) time for all patients were 15 months 95% confidence interval (CI): 10.9-19.1 months and 27 months (95% CI: 15.9-38.1 months), respectively. Patients with low PNI had significantly shorter median PFS (11 vs 20 months, p=0.001) and OS (17 vs 40 months, p=0.001) than those with high PNI. In multivariate analysis, PNI was shown as an independent predictor on both OS and PFS. Moreover, Eastern Cooperative Oncology Group-Performance Status was shown as an independent predictor for OS and International Metastatic Renal-Cell Carcinoma Database Consortium-score for PFS. Conclusion:Low PNI could be a significant prognostic marker for survival in mRCC patients who have received tyrosine kinase inhibitors as first-line target therapy.
Objective
Prostate cancer is the second leading cause of cancer death in men. Androgen deprivation therapy (ADT) has been the primary therapeutic approach for treatment of prostate cancer. ...However,nearly all patients develop the castration-resistant disease . We evaluated real-world data with abiraterone and enzalutamide treatment. By this data, we aimed to analyze whether that prior short response to ADT could predict response to subsequent therapy with androgen receptor axis targeted agent (ARATA).
Material and Method
We collected data from two cancer centers, 151 consecutive patients with treated abiraterone or enzalutamide in the first line of metastatic castration resistant prostat cancer (mCRPC) setting were included. The patients who received docetaxel in castration naive setting is also included. Time to castration resistance (TTCR) was defined as the duration from the initial to failure of primary ADT.
Results
Patients with treated ARATA were divided into two groups according to the time to castration resistance (TTCR). Patients who became resistant to ADT up to one year had a median PFS of 6.6 months, compared to median PFS of 13.3 months for patients who responded ADT for more than 1 year. (p = 0.002). In the post-docetaxel setting, median PFS is 12.6 months of patients with treated ARATA who had TTCR for more than one year, and median PFS is 6.6 months in those who had TTCR less than one year (p = 0.007).Univariate and multivariate analyses were performed to determine the clinical factors on ARATA outcomes. Eastern Cooperative Oncology Group (ECOG) performance status(PS), median prostate-specific antigen(PSA) and time to CRPC were significantly predicted outcomes of ARATA on multivariate analysis.
Conclusion
TTCR is also a predictor for PFS of the patients who were treated ARATA both whole cohort and post-docetaxel.
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