Clinical role of ^(18)F-FDG PET/CT-based simultaneous modulated accelerated radiotherapy treatment planning for locally advanced nasopharyngeal carcinoma

Objective The aim of this study was to compare the long-term local control, overall survival, and late toxicities of positron emission tomography/computed tomography （PET/CT）-guided dose escalation radio- therapy versus conventional radiotherapy in the concurrent chemoradiotherapy treatment of locally ad- vanced nasopharyngeal carcinoma （NPC）. Methods Atotal of 48 patients with stage IIl-IVa NPC were recruited and randomly administered PET/CT- guided dose escalation chemoradiotherapy （group A） or conventional chemoradiotherapy （group B）. The dose-escalation radiotherapy was performed using the simultaneous modulated accelerated radiotherapy technique at prescribed doses of 77 gray （Gy） in 32 fractions （f） to the gross target volume （GTV）： planning target volume （PTV） 1 received 64 Gy/32 f, while PTV2 received 54.4 Gy/32 f. Patients in group B received uniform-dose intensity-modulated radiotherapy, PTV1 received 70 Gy/35 f and PTV2 received 58 Gy/29 f. Concurrent chemotherapy consisted of cisplatin [20 mg/m2 intravenous （IV） on days 1-4] and docetaxel （75 mg/m2 IV on days 1 and 8） administered during treatment weeks 1 and 4. All patients received 2-4 cycles of adjuvant chemotherapy of the same dose and drug regimen. Results The use of fluorine-18-fluorodeoxyglucose （18F-FDG） PET/CT significantly reduced the treat- ment volume delineation of the GTV in 83.3% （20/24） of patients. The 5-year local recurrence-free survival rates of the two groups were 100% and 79.2%, respectively （P = 0.019）. The 5-year disease free survival （DFS） rates were 95.8% and 75.0%, respectively （P = 0.018）. The 5-year local progression-free survival and DFS rates were significantly different. The 5-year overall survival （OS） rates were 95.8% and 79.2%, re- spectively. Differences in OS improvement were insignificant （P = 0.079）. Late toxicities were similar in the two groups. The most common late toxicities of the two arms were grade 1-2 skin dystrophy, xerostomia, subcutaneous fibrosis, and hearing loss. There were no cases of grade 4 late toxicity. Conclusion The use of 18F-FDG PET/CT-guided dose escalation radiotherapy is well tolerated and can reduce local recurrence rates for patients with locally advanced NPC compared to conventional chemora- diotherapy.

Central nervous system efficacy of aumolertinib versus gefitinib in patients with untreated,EGFR-mutated,advanced non-small cell lung cancer:data froma randomized phase III trial(AENEAS)

Background:The initial randomized,double-blinded,actively controlled,phase III ANEAS study(NCT03849768)demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal growth factor receptor(EGFR)-mutated advanced non-small cell lung cancer(NSCLC).Metastatic disease in the central nervous system(CNS)remains a challenge in the management of NSCLC.This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study.Methods:Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double-blinded fashion.Patients with asymptomatic,stable CNS metastases were included.Follow-up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months,then every 12weeks.CNS responsewas assessed by a neuroradiological blinded,independent central review(neuroradiological-BICR).The primary endpoint for this subgroup analysis was CNS progression-free survival(PFS).Results:Of the 429 patients enrolled and randomized in the ANEAS study,106 patients were found to have CNS metastases(CNS Full Analysis Set,cFAS)at baseline by neuroradiological-BICR,and 60 of them had CNS target lesions(CNS Evaluable for Response,cEFR).Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS(29.0 vs.8.3 months;hazard ratio[HR]=0.31;95%confidence interval[CI],0.17-0.56;P<0.001)and cEFR(29.0 vs.8.3 months;HR=0.26;95%CI,0.11-0.57;P<0.001).The confirmed CNS overall response rate in cEFRwas 85.7%and 75.0%in patients treated with aumolertinib and gefitinib,respectively.Competing risk analysis showed that the estimated probability of CNS progression without prior non-CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNSmetastases at baseline.No new safety findings were observed.Conclusions:These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR-mutated advanced NSCLC with baseline CNS metastases.

Overexpression of RBM34 Promotes Tumor Progression and Correlates with Poor Prognosis of Hepatocellular Carcinoma

Background and Aims:Emerging evidence suggests that RNA-binding motif(RBM)proteins are involved in hepatocarcinogenesis and act either as oncogenes or tumor suppressors.The objective of this study was to investigate the role of RBM34,an RBM protein,in hepatocellular carcinoma(HCC).Methods:We first examined the expression of RBM34 across cancers.The correlation of RBM34 with clinicopathological features and the prognostic value of RBM34 for HCC was then investigated.Functional enrichment analysis of RBM34-related differentially expressed genes(DEGs)was performed to explore its biological function.RNA sequencing(RNA-seq)was applied to identify downstream genes and pathways affected upon RBM34 knockout.The correlation of RBM34 with immune characteristics was also analyzed.The oncogenic function of RBM34 was examined in in vitro and in vivo experiments.Results:RBM34 was highly expressed in hepatocellular carcinoma and correlated with poor clinicopathological features and prognosis.RBM34 was positively associated with tumor immune cell infiltration,biomarkers of immune cells,and immune checkpoint expression.A positive correlation was also observed between RBM34,T cell exhaustion,and regulatory T cell marker genes.Knockout of RBM34 significantly inhibited cell proliferation,migration,and xenograft tumor growth,and sensitized HCC cells to sorafenib treatment.RBM34 inhibition reduced FGFR2 expression and affected PI3K-AKT pathway activation in HCC cells.Conclusions:Our study suggests that RBM34 may serve as a new prognostic marker and therapeutic target of HCC.

Pulsed low-dose rate radiotherapy has an improved therapeutic effect on abdominal and pelvic malignancies

Until now,there has been a lack of standard and effective treatments for patients with recurrent malignant tumors or abdominal and pelvic malignancies with extensive invasion(Morris,2000).Generally,these patients face problems such as inability to undergo surgery or chemotherapy resistance(Combs et al.,2016).Re-radiotherapy has achieved a prominent place in the treatment of patients who have received radiotherapy previously and developed in-field recurrences(Straube et al.,2018).However,re-radiotherapy is very complicated,requiring comprehensive consideration of appropriate radiation dose,interval from first radiotherapy,boundary of the radiotherapy target area,and damage to surrounding normal tissues(Straube et al.,2019).In other words,it is necessary to focus on the protection of surrounding normal tissues while maximizing the eflFicacy of re-radiotherapy in such patients.