Current management of chemotherapy-induced neutropenia in adults:key points and new challenges

Chemotherapy-induced neutropenia(CIN)is a potentially fatal and common complication in myelosuppressive chemotherapy.The timing and grade of CIN may play prognostic and predictive roles in cancer therapy.CIN is associated with older age,poor functional and nutritional status,the presence of significant comorbidities,the type of cancer,previous chemotherapy cycles,the stage of the disease,specific chemotherapy regimens,and combined therapies.There are many key points and new challenges in the management of CIN in adults including:(1)Genetic risk factors to evaluate the patient’s risk for CIN remain unclear.However,these risk factors urgently need to be identified.(2)Febrile neutropenia(FN)remains one of the most common reasons for oncological emergency.No consensus nomogram for FN risk assessment has been established.(3)Different assessment tools[e.g.,Multinational Association for Supportive Care in Cancer(MASCC),the Clinical Index of Stable Febrile Neutropenia(CISNE)score model,and other tools]have been suggested to help stratify the risk of complications in patients with FN.However,current tools have limitations.The CISNE score model is useful to support decision-making,especially for patients with stable FN.(4)There are still some challenges,including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN.In view of the current reports,our group discusses the key points,new challenges,and management of CIN.

The Binarity of Early-type Stars from LAMOST medium-resolution Spectroscopic Survey

Massive binaries play significant roles in many fields.Identifying massive stars,particularly massive binaries,is of great importance.In this paper,by adopting the technique of measuring the equivalent widths of several spectral lines,we identified 9382 early-type stars from the LAMOST medium-resolution survey and divided the sample into four groups,T1(~O-B4),T2(~B5),T3(~B7)and T4(~B8-A).The relative radial velocities RVrelwere calculated using Maximum Likelihood Estimation.The stars with significant changes of RVreland at least larger than 15.57 km s-1 were identified as spectroscopic binaries.We found that the observed spectroscopic binary fractions for the four groups are 24.6%±0.5%,20.8%±0.6%,13.7%±0.3%and 7.4%±0.3%,respectively.Assuming that orbital period(P)and mass ratio(q)have intrinsic distributions as f(P)∝Pπ(1<P<1000 days)and f(q)∝qκ(0.1<q<1),respectively,we conducted a series of Monte-Carlo simulations to correct observational biases for estimating the intrinsic multiplicity properties.The results show that the intrinsic binary fractions for the four groups are 68%±8%,52%±3%,44%±6%and 44%±6%,respectively.The best estimated values forπare-1±0.1,-1.1±0.05,-1.1±0.1 and-0.6±0.05,respectively.Theκcannot be constrained for groups T1 and T2 and is-2.4±0.3 for group T3 and-1.6±0.3 for group T4.We confirmed the relationship of a decreasing trend in binary fractions toward late-type stars.No correlation between the spectral type and orbital period distribution has been found yet,possibly due to the limitation of observational cadence.

中国胃癌肝转移患者临床诊疗特征及预后分析:全国多中心队列研究(RECORD研究)

Despite surgical improvements and pharmacological advances,management of late-stage gastric cancer patients,especially those with hepatic metastasis remains challenging[1–3].Although nationwide registry data from SEER(Surveillance,Epidemiology,and End Results)[4]and the Nordic database[5]in Western countries have provided epidemiological information for patients with gastric cancer liver metastasis(GCLM),little is known about the detailed clinical characteristics.

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.

The real-world study of the clinical characteristics,diagnosis,and treatment of advanced pancreatic cancer in China

Objective:Real-world diagnostic and treatment data for pancreatic cancer in China are lacking.As such,the present study investigated the clinical characteristics,diagnosis,and treatment of advanced pancreatic cancer(including locally advanced and metastatic disease)in the Hospital-based Advanced Pancreatic Cancer Cohort in China of the China Pancreas Data Center database.Methods:A total of 5349 Chinese patients with advanced pancreatic cancer were identified from a database.The entire course of real-world pancreatic cancer management was analyzed.Results:The proportion of patients with advanced pancreatic cancer was higher among males than females(62.4%vs 37.6%,respectively).Patients typically had a history of hypertension(30.8%),diabetes(21.6%),and cholangitis(20.2%).Abdominal pain(51.6%),abdominal distension(27.1%),jaundice(20.1%),and weight loss(16.3%)were the main symptoms observed in patients with advanced pancreatic cancer in this cohort.Serum carbohydrate antigen(CA)19-9 is one of the most common tumor markers.In the present study,2562 patients underwent first-line therapy.The median progression-free survival(PFS)for patients undergoing first-line therapy was 4.1 months.The major options for first-line therapy included gemcitabine(GEM)plus S-1(GS/X)(23.4%),nab-paclitaxel plus GEM(AG)(18.1%),oxaliplatin,irinotecan,and leucovorin-modulated fluorouracil(FOLFIRINOX;11.9%),nab-paclitaxel plus S-1(AS)(8.9%),and GEM combined with oxaliplatin/cisplatin(GEMOX/GP)(7.6%).The AS and GS/X regimens were associated with the highest PFS rates.Conclusion:This is the first study to report multicenter,real-world data regarding advanced pancreatic cancer in China.Results revealed that real-world treatment options differed from guideline recommendations,and PFS was shorter than that in previously reported data.Improving intelligent follow-up systems and standardizing diagnosis and treatment of pancreatic cancer is recommended.

SALIRI-based(raltitrexed plus irinotecan)therapy as a second-line treatment for patients with metastatic colorectal cancer(SALLY):A prospective,multicenter,non-interventional,registry study

Primary chemotherapy options for colorectal cancer(CRC)involve four key drugs:fluorouracils(5-FU),oxaliplatin,irinotecan and raltitrexed.The first-line regimen consists of 5-FU and leucovorin combined with oxaliplatin(FOLFOX),while the second-line regimen involves 5-FU and leucovorin combined with irinotecan(FOLFIRI)for metastatic CRC(mCRC)in China[1].

Nucleolar stress promotes and cooperates with ferroptosis to suppress cancer growth

Dear Editor,Ferroptosis is a non-apoptotic form of regulated cell death driven by iron-dependent phospholipid peroxidation(Chen et al.,2021).The tumor suppressor p53 promotes ferroptosis by increasing lipid peroxidation and reducing glutathione(GSH)levels,while it also inhibits ferroptosis by activating the expression of several ferroptosis repressors,such as FSP1 and iPLA2β,indicating the complexity of p53’s function in modulating ferroptosis in a cell-specific or context-specific manner(Liu and Gu,2022).

Adjuvant chemotherapy may be unnecessary for ypT0-2N0 gastric cancer patients after neoadjuvant chemotherapy and curative gastrectomy

To the Editor:Gastric cancer(GC)is the sixth most common type of cancer and the third most common cause of cancer-related deaths worldwide.[1]Due to the lack of typical clinical symptoms in the early stage of GC,most patients have advanced-stage disease at the time of initial treatment and have a poor prognosis.The rate of radical resection is low.Even after radical resection,recurrence or death occurs in 50%to 90%of patients,and the 5-year overall survival(OS)rate is less than 30%.[2]Therefore,various multimodal strategies,which would presumably reduce the risk of cancer recurrence and improve survival,are being explored to eliminate any residual tumors and micro-metastases.Neoadjuvant chemotherapy(NAC)followed by surgery is recommended as the standard of care for patients with localized resectable GC.

Paclitaxel liposome for injection (Lipusu) plus cisplatin versus gemcitabine plus cisplatin in the first-line treatment of locally advanced or metastatic lung squamous cell carcinoma: A multicenter, randomized, open-label, parallel controlled clinical study

Background:Lipusu is the first commercialized liposomal formulation of pacli-taxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma(LSCC)in a small-scale study.Here,we conducted a multicenter,randomized,phase 3 study to compare the efficacy and safety of cis-platin plus Lipusu(LP)versus cisplatin plus gemcitabine(GP)as first-line treat-ment in locally advanced or metastatic LSCC.Methods:Patients enrolled were aged between 18 to 75 years,had locally advanced(clinical stage IIIB,ineligible for concurrent chemoradiation or surgery)or metastatic(Stage IV)LSCC,had no previous systemic chemother-apy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors(version 1.1)before administration of the trial drug.The primary endpoint was progression-free survival(PFS).The secondary endpoints included objective response rate(ORR),disease control rate(DCR),overall survival(OS),and safety profiles.To explore the possible predictive value of plasma cytokines for LP treatment,plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology.The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses.Results:The median duration of follow-up was 15.4 months.237 patients in the LP group and 253 patients in the GP group were included in the per protocol set(PPS).In the PPS,the median PFS was 5.2 months versus 5.5 months in the LP and GP group(hazard rtio[HR]:1.03,P=0.742)respectively.The median OS was 14.6 months versus 12.5 months in the LP and GP group(HR:0.83,P=0.215).The ORR(41.8%versus 45.9%,P=0.412)and DCR(90.3%versus 88.1%,P=0.443)were also similar between the LP and GP group.A significantly lower proportion of patients in the LP group experienced adverse events(AEs)leading to treatment interruptions(10.9%versus 26.4%,P<0.001)or treatment termination(14.3%versus 23.1%,P=0.011).The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR,and 15 cytokines were associated with improved PFS,with 14 cytokines,including TNF-a,IFN-y,IL-6,and IL-8,demonstrating an overlapping trend.Conclusion:The LP regimen demonstrated similar PFS,OS,ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles.The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen.

MDM2 inhibitors in cancer immunotherapy:Current status and perspective

Murine double minute 2(MDM2)plays an essential role in the cell cycle,apoptosis,DNA repair,and oncogene activation through p53-dependent and p53-independent signaling pathways.Several preclinical studies have shown that MDM2 is involved in tumor immune evasion.Therefore,MDM2-based regulation of tumor cell-intrinsic immunoregulation and the immune microenvironment has attracted increasing research attention.In recent years,im-mune checkpoint inhibitors targeting PD-1/PD-L1 have been widely used in the clinic.Howev-er,the effectiveness of a single agent is only approximately 20%-40%,which may be related to primary and secondary drug resistance caused by the dysregulation of oncoproteins.Here,we reviewed the role of MDM2 in regulating the immune microenvironment,tumor immune evasion,and hyperprogression during immunotherapy.In addition,we summarized preclinical and clinical findings on the use of MDM2 inhibitors in combination with immunotherapy in tu-mors with MDM2 overexpression or amplification.The results reveal that the inhibition of MDM2 could be a promising strategy for enhancing immunotherapy.