Future oncology最新文献

Patients with relapsed or refractory (r/r) acute myeloid leukemia (AML) have very poor long-term outcomes. Allogeneic stem cell transplantation (allo-SCT) can potentially cure some of these patients who are able to achieve a second or greater remission with salvage chemotherapy. Unfortunately, several barriers exist to transplantation and not all patients with r/r AML are able to proceed to allo-SCT. Therefore, novel therapies to decrease the risk of relapse in these patients are urgently needed. Wilms tumor 1 (WT1) protein has emerged as an encouraging vaccine target in AML due to its overexpression in leukemic blast cells and near absence in normal hematopoietic cells. Maintenance therapy with galinpepimut-S, a multivalent heteroclitic WT1 peptide vaccine, holds promise in early phase trials, in patients with AML by inducing a strong innate immune response against the WT1 antigen, leading to the design of this international, open-label, randomized clinical trial, named REGAL. Clinical trial registration: https://clinicaltrials.gov/study/NCT04229979. The clinical trial identifier is NCT04229979.

Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation is prognostic of poor survival for patients with non-small cell lung cancer (NSCLC). KRAS G12C mutations occur in 13% of NSCLC cases and despite the frequency of this mutation, advances in drug development against KRAS have historically been impeded due to the extremely high affinity of KRAS for guanosine triphosphate (GTP) and the lack of a binding pocket on the surface of KRAS that is suitable for drug binding. Sotorasib, a first-in-class, highly selective KRAS G12C inhibitor overcomes this issue by irreversibly binding in the switch-II pocket. Sotorasib was granted accelerated FDA approval for the treatment of KRASG12C-mutated locally advanced/metastatic NSCLC who have received at least one prior systemic therapy. This review summarizes the pharmacology, clinical efficacy, adverse effects, and clinical considerations of sotorasib.

Although concurrent Chemoradiotherapy (cCRT) is presently the standard intervention for patients with inoperable, locally advanced Esophageal Squamous Cell Carcinoma (ESCC), it has been associated with poor long-term survival outcomes. Notably, Immune Checkpoint Inhibitors (ICIs) improve the long-term survival of Esophageal Cancer (EC) patients, with manageable Adverse Effects (AEs). Herein, 90 patients with residual pathology after radical simultaneous Radiotherapy (RT) for inoperable/refused-to-operate ESCC were enrolled and randomized into two treatment groups (Chemotherapy+immunotherapy and chemotherapy alone) in a 2:1 ratio. This study will also discuss the value of immunotherapy in improving long-term survival outcomes in patients with pathological residuals after concurrent RT for locally advanced, inoperable ESCC.Clinical trial registration: http://www.chictr.org.cn/identifier is ChiCTR2200063345.

Background: This study aimed to compare the efficacy of CDK4/6 inhibitors plus endocrine therapy in two groups of patients with HR-positive/HER2-negative metastatic breast cancer: those with symptomatic, high tumor burden disease and those with asymptomatic disease.

Design and methods: This retrospective study included 193 patients who received either ribociclib or palbociclib in combination with first-line ET. Patients were divided into symptomatic and asymptomatic groups and compared regarding baseline characteristics and progression-free survivals (PFS).

Results: Symptomatic patients had a significantly shorter mPFS than asymptomatic patients (22.7 months vs. 35.0 months, p = 0.009). Among symptomatic patients, those treated with ribociclib had a longer mPFS than those treated with palbociclib (28.26 months vs. 17.18 months, p = 0.021). Multivariate analysis identified the symptomatic disease and liver metastasis as independent predictors of shorter mPFS (HR; 1.835, 95% CI; 1.146-2.939 and HR; 2.433, 95% CI; 1.329-4.454, respectively).

Conclusion: Our analysis revealed that although symptomatic individuals who underwent CDK4/6 inhibitor plus ET experienced a significant reduction in mPFS durations compared to asymptomatic patients, the 22-month mPFS indicated that CDK4/6 inhibitor plus ET is an effective treatment option.

Aim: To investigate current management of advanced epithelial ovarian cancer (OC) in the UK.Materials & methods: A cross-sectional survey with 55 healthcare professionals involved in the care of OC patients was conducted via telephone/videoconference in March/May 2023.Results: Respondents reported that homologous recombination deficiency (HRD) status and brca mutations were routinely tested before planning maintenance treatment. All respondents agreed that cytoreductive surgery should be considered at first recurrence, and 65% recommended using the Descriptive Evaluation of Preoperative Selection Criteria for Operability in Recurrent Ovarian Cancer (DESKTOP) III criteria to guide secondary cytoreduction. Platinum responders typically receive poly (ADP-ribose) polymerase inhibitor maintenance therapy, regardless of HRD status.Conclusion: Respondents reinforce that most primary OC patients in the UK have known HRD and BRCA mutation status, and the role of secondary cytoreduction is increasingly recognized.

Introduction: Allogeneic hematopoietic stem cell transplantation (HCT) improves survival of patients with hematologic malignancies. A growing responsibility exists to identify and address long-term morbidity and symptom burden. We investigated metabolic syndrome and symptom burden in adult HCT survivors.

Methods: We analzyed adults with hematologic disorders who were treated with allogeneic HCT at our institution from June 2018-November 2022. We used standard criteria for metabolic syndrome with body mass index (BMI) as a surrogate for waist circumference. We assessed symptom burden using the National Comprehensive Cancer Network Survivorship Assessment. The Short Physical Performance Battery and Short Blessed Test were used to investigate physical function and cognition, respectively.

Results: A total of 152 patients were included. Median age was 61 years, 59% were male, and the most common disorder was acute myeloid leukemia (48%). 64 patients developed metabolic syndrome post-transplant. The most commonly affected symptom domains were fatigue (51%), sleep (45%), and cognitive function (42%). Additionally, 34% and 7% of patients had objectively impaired functional capacity and cognition, respectively.

Conclusion: Recipients of allogeneic HCT have a high incidence of metabolic syndrome, symptom burden, and impaired physical function.

Aim: We conducted a meta-analysis of published randomized controlled trials to compare the effectiveness and safety of eribulin versus paclitaxel for patients with breast cancer.

Methods: We systematically searched multiple databases including Cochrane, PubMed, Medline, and Embase. The primary outcomes analyzed were overall survival (OS), complete response (CR), partial response (PR), stable disease (SD), and adverse events (AEs). These outcomes were evaluated using RevMan5.3 software.

Results: A total of 5 studies were included in the analysis. Compared to paclitaxel plus other chemotherapy drugs, eribulin plus other chemotherapy drugs not only extended the overall survival of patients but also improved the disease control rate (DCR) [risk ratio (RR) 0.98, (95% confidence intervals (CI): 0.70, 1.38), p = 0.92]. Hematological system diseases [RR 1.18 (95% CI: 1.07, 1.31), p = 0.002] were the most frequently observed adverse event with eribulin, while paclitaxel was more likely to cause nervous system lesion [RR 0.66 (95% CI: 0.54, 0.80), p < 0.0001].

Conclusion: Compared with paclitaxel plus other chemotherapy drugs, eribulin plus other chemotherapy drugs can also prolong the PFS and OS of BC patients. Our recommendation is to use eribulin plus other chemotherapy drugs to treat advanced BC and to continuously monitor and manage the drug-related adverse events.

Background: Previous studies on brain tumors have been performed on the nuclear genome, but limited studies have been reported on the mitochondrial genome. The mitochondrial sirtuin (SIRT3/SIRT4/SIRT5) has been mutated in different cancers. Limited studies have been performed on brain tumors. Isocitrate dehydrogenase (IDH) is an important marker, and polymorphism in the IDH gene has been reported to differentiate the brain tumor subtypes.

Aim: The present study was designed to screen mitochondrial sirtuins and IDH polymorphisms in brain tumor patients.

Methodology: One thousand blood samples were collected (500 brain tumor patients and 500 controls). Two SNPs for each gene SIRT3 (rs12226697, rs570591), SIRT4 (rs184496260, 1925909), SIRT5 (rs2841522, rs2841523), and one SNP for IDH (rs11554137) was screened using Tetra-ARMS PCR.

Results: Logistic regression showed that the mutant genotype of selected SNPs was associated with increased disease incidence compared to wild type. Haplotype analysis and linkage disequilibrium (LD) showed a strong LD in brain tumor patients. Kaplan-Meier analysis showed that mutant allele frequency was found to be associated with a significant decrease in the survival of brain tumor patients.

Conclusion: The present study showed that the mutant allele of selected mitochondrial sirtuins' SNP was associated with increased brain tumor risk.