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Impact of the COVID-19 Pandemic on Cancer Patients: Experience of the medical oncology department of CHU HASSAN II Fez.

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Journal of Cancer Therapy 2024年第3期15卷 83-91页

作者： Khadija Hinaje Oumaima Talbi Lamiae Amaadour Karima Oualla Zineb Benbrahim Samia Arifi Nawfel Mellas department of medical oncology Hassan II University Hospital University Sidi Mohamed Ben Abdellah Fez Morocco

Introduction: In December 2019, COVID 19 spread worldwide, but did not officially start in MOROCCO until March 02, 2020. Since then, this pandemic has significantly impacted the health status of patients in general and cancer patients in particular. The main objective of our study is to evaluate the prognosis of patients treated for cancer and infected with COVID-19. Material and method: A descriptive study with prospective collection was carried out at the medical oncology department of CHU Hassan II in FEZ over a period of two years, from March 2020 to March 2022. Data was carried out on the software SPSS. Results: One hundred cancer patients tested positive for COVID-19 infection and were collected within our department. The average age was 56 years [22-91]. The sex ratio was 1.2. Patients with breast cancer were the most affected by this infection (34%). The clinical symptomatology was dominated by the respiratory syndrome (45%).The diagnosis was made through thoracic CT scan in 62% of cases. 76% of patients were in a metastatic stage. 96% of patients were undergoing oncological treatment. For symptomatique patients, the standard treatment approach involved using antibiotics in 76% of cases. Evolution was marked by recovery in 79% of patients, with a death rate of 12% in this cancer patient population. Conclusion: COVID-19 infection is particularly severe in cancer patients. Mortality among these patients remains high and is associated with overall patient characteristics. However, anticancer treatments have not shown deleterious effects on the course of COVID-19.

关键词： COVID-19 Cancer. SARS-CoV-2

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New clinical trial design in precision medicine:discovery,development and direction

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1293-1321页

作者： Xiao-Peng Duan Bao-Dong Qin Xiao-Dong Jiao Ke Liu Zhan Wang Yuan-Sheng Zang department of medical oncology Changzheng HospitalNaval Medical UniversityShanghaiChina

In the era of precision medicine,it has been increasingly recognized that individuals with a certain disease are complex and different from each other.Due to the underestimation of the significant heterogeneity across participants in traditional"one-sizefits-all"trials,patient-centered trials that could provide optimal therapy customization to individuals with specific biomarkers were developed including the basket,umbrella,and platform trial designs under the master protocol framework.In recent years,the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous opportunities.Despite the rapid increase in the number of basket,umbrella,and platform trials,the current clinical and research understanding of these new trial designs,as compared with traditional trial designs,remains limited.The majority of the research focuses on methodologies,and there is a lack of in-depth insight concerning the underlying biological logic of these new clinical trial designs.Therefore,we provide this comprehensive review of the discovery and development of basket,umbrella,and platform trials and their underlying logic from the perspective of precision medicine.Meanwhile,we discuss future directions on the potential development of these new clinical design in view of the"Precision Pro","Dynamic Precision",and"Intelligent Precision".This review would assist trial-related researchers to enhance the innovation and feasibility of clinical trial designs by expounding the underlying logic,which be essential to accelerate the progression of precision medicine.

关键词： clinical approval successive

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Evidence-Based Dampness-Heat ZHENG(Syndrome) in Cancer: Current Progress toward Establishing Relevant Animal Model with Pancreatic Tumor

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Chinese Journal of Integrative Medicine 2024年第1期30卷 85-95页

作者： JIAO Ju-ying CHENG Chien-shan CAO Zhang-qi CHEN Lian-yu CHEN Zhen department of Integrative oncology Fudan University Shanghai Cancer CenterShanghai(200032)China department of oncology Shanghai Medical CollegeFudan UniversityShanghai(200032)China

Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG(syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG(DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted animal model to study this core syndrome in vivo. The shortage of animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer animal model.

关键词： cancer Chinese medicine syndrome ZHENG dampness-heat syndrome animal model pancreatic tumor evaluation methods

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Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract

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World Journal of Gastrointestinal oncology 2024年第4期16卷 1166-1179页

作者： Sebastián Díaz-López Jerónimo Jiménez-Castro Carlos Enrique Robles-Barraza Carlos Ayala-de Miguel Manuel Chaves-Conde medical oncology department Hospital Universitario ValmeSeville 41014AndalucíaSpain

Mixed neuroendocrine non-neuroendocrine neoplasms(MiNENs)are a hetero-geneous group of malignant neoplasms that can settle in the gastroenteropan-creatic tract.They are composed of a neuroendocrine(NE)and a non-NE compo-nent in at least 30%of each tumour.The non-NE component can include different histological combinations of glandular,squamous,mucinous and sarcomatoid phenotypes,and one or both of the components can be low-or high grade malignant.Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion,and the lack of specific clinical trials is the main reason why their management is difficult.The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data.It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that,due to their low incidence,will require long recruitment periods.

关键词： Mixed neuroendocrine non-neuroendocrine neoplasms Mixed adenoneuroendocrine carcinomas Mixed tumours Gastroenteropancreatic Treatment Etiology Diagnosis

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Construction of an immune-related gene signature for overall survival prediction and immune infiltration in gastric cancer

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World Journal of Gastrointestinal oncology 2024年第3期16卷 919-932页

作者： Xiao-Ting Ma Xiu Liu Kai Ou Lin Yang department of medical oncology Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

BACKGROUND Treatment options for patients with gastric cancer(GC)continue to improve,but the overall prognosis is poor.The use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has gradually become the new standard treatment option at present,and there is an urgent need to identify valuable biomarkers to classify patients with different characteristics into subgroups.AIM To determined the effects of differentially expressed immune-related genes(DEIRGs)on the development,prognosis,tumor microenvironment(TME),and treatment response among GC patients with the expectation of providing new biomarkers for personalized treatment of GC populations.METHODS Gene expression data and clinical pathologic information were downloaded from The Cancer Genome Atlas(TCGA),and immune-related genes(IRGs)were searched from ImmPort.DEIRGs were extracted from the intersection of the differentially-expressed genes(DEGs)and IRGs lists.The enrichment pathways of key genes were obtained by analyzing the Kyoto Encyclopedia of Genes and Genomes(KEGGs)and Gene Ontology(GO)databases.To identify genes associated with prognosis,a tumor risk score model based on DEIRGs was constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox regression.The tumor risk score was divided into high-and lowrisk groups.The entire cohort was randomly divided into a 2:1 training cohort and a test cohort for internal validation to assess the feasibility of the risk model.The infiltration of immune cells was obtained using‘CIBERSORT,’and the infiltration of immune subgroups in high-and low-risk groups was analyzed.The GC immune score data were obtained and the difference in immune scores between the two groups was analyzed.RESULTS We collected 412 GC and 36 adjacent tissue samples,and identified 3627 DEGs and 1311 IRGs.A total of 482 DEIRGs were obtained.GO analysis showed that DEIRGs were mainly distributed in immunoglobulin complexes,receptor ligand activity,and signaling receptor activators.KEGG pathway analys

关键词： Differentially expressed immune-related gene Immunotherapy Gastric cancer Risk score

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Chinese Medicine Combined with Adjuvant Chemotherapy for Improving Myelosuppression in Colorectal Cancer Patients: A Systematic Review and Network Meta-Analysis

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Chinese Journal of Integrative Medicine 2024年第7期30卷 643-652页

作者： LI Rui ZHANG Tong YAN Shao-hua YAN Yun-zi DING Ya-cong WANG Yan-song YANG Yu-fei department of oncology China Academy of Chinese Medical Sciences Xiyuan Hospital department of oncology Dongfang Hospital Beijing University of Chinese Medicine Graduate School Beijing University of Chinese Medicine

Objective: To assess the effectiveness of Chinese herbal medicine(CHM) combined with adjuvant chemotherapy on myelosuppression for colorectal cancer(CRC) patients using network meta-analysis(NMA). Methods: Literature searches in both international(PubMed, Embase, Web of Science, and Cochrane Library) and Chinese(China Science and Technology Journal Database, Wanfang Data, China National Knowledge Infrastructure) databases for relevant randomized controlled trials(RCTs) were conducted from inception until October 10, 2022. We included RCTs of patients who received CHM combined with chemotherapy, including FOLFOX, XELOX, FOLFIRI, and other relevant regimens in the CHM treatment group. The outcomes included the incidence of myelosuppression, leukopenia, hemoglobin reduction, and thrombocytopenia. Two reviewers independently screened the databases, extracted the data, and assessed the risk of bias and credibility of evidence. RevMan 5.4.1 software and STATA 14.0 were used to perform the NMA. Results: A total of 31 RCTs were included, published from 2008 to 2021 in Chinese. Among these, 2,314 participants comparing the following 9 CHMs were identified: Shengbai Recipe(SBR), Bazhen Decoction(BZD), Jianpi Jiedu Recipe(JJR), Jianpi Recipe(JR), Compound Cantharis Capsule(CCC), Zaofan Pill(ZFP), Guilu Erxian Gel(GL), Buzhong Tiaogan Decoction(BZ), and Qiamagu Capsule(QM). The results of NMA found an indirect comparison. Based on the surface under the cumulative ranking curve(SUCRA), the ZFP+ chemotherapy group had the lowest incidence of myelosuppression, with an odds ratio(OR) of 0.08 [95% confidence interval(CI): 0.01, 0.76], whereas the GL+ chemotherapy group had the lowest incidence of leukopenia, hemoglobin reduction, and thrombocytopenia, with an OR of 5.25(95% CI: 2.41, 11.43), 4.66(95% CI: 2.23, 9.72), and 0.27(95% CI: 0.13, 0.54), respectively. Moreover, BZD + chemotherapy could alleviate leukopenia, hemoglobin reduction, and thrombocytopenia(P<0.01). Pairwise comparison showed that there was no difference in the

关键词： Chinese herbal medicine colorectal cancer network meta-analysis systematic review myelosuppression chemotherapy

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New perspectives on biology,disease progression,and therapy response of head and neck cancer gained from single cell RNA sequencing and spatial transcriptomics

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oncology Research 2024年第1期32卷 1-17页

作者： GERWIN HELLER THORSTEN FUEREDER ALEXANDER MICHAEL GRANDITS ROTRAUD WIESER Division of oncology Department of Medicine IMedical University of ViennaVienna1090Austria Ludwig Boltzmann Institute for Hematology and oncology Medical University of ViennaVienna1090Austria

Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent cancers worldwide.The main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma virus.Approved therapeutic options comprise surgery,radiation,chemotherapy,targeted therapy through epidermal growth factor receptor inhibition,and immunotherapy,but outcome has remained unsatisfactory due to recurrence rates of~50%and the frequent occurrence of second primaries.The availability of the human genome sequence at the beginning of the millennium heralded the omics era,in which rapid technological progress has advanced our knowledge of the molecular biology of malignant diseases,including HNSCC,at an unprecedented pace.Initially,microarray-based methods,followed by approaches based on next-generation sequencing,were applied to study the genetics,epigenetics,and gene expression patterns of bulk tumors.More recently,the advent of single-cell RNA sequencing(scRNAseq)and spatial transcriptomics methods has facilitated the investigation of the heterogeneity between and within different cell populations in the tumor microenvironment(e.g.,cancer cells,fibroblasts,immune cells,endothelial cells),led to the discovery of novel cell types,and advanced the discovery of cell-cell communication within tumors.This review provides an overview of scRNAseq,spatial transcriptomics,and the associated bioinformatics methods,and summarizes how their application has promoted our understanding of the emergence,composition,progression,and therapy responsiveness of,and intercellular signaling within,HNSCC.

关键词： Head and neck squamous cell carcinoma Tumor microenvironment Immunotherapy Gene expression Omics

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Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial

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World Journal of Gastrointestinal oncology 2024年第2期16卷 386-397页

作者： Vilma Pacheco-Barcia Sara Custodio-Cabello Fatima Carrasco-Valero Magda Palka-Kotlowska Axel Mariño-Mendez Alberto Carmona-Bayonas Javier Gallego A J Muñoz Martín Paula Jimenez-Fonseca Luis Cabezon-Gutierrez department of medical oncology Hospital Universitario de TorrejonMadrid 28850Spain department of Internal Medicine Hospital Universitario de TorrejonMadrid 28850Spain department of medical oncology Hospital Universitario Central de AsturiasOviedo 33011Spain department of medical oncology Hospital Universitario Morales MeseguerUniversity of MurciaMurcia 30001Spain department of medical oncology Hospital General Universitario de ElcheElche 03202Spain department of medical oncology Hospital General Universitario Gregorio MarañónUniversidad Complutense MadridMadrid 28007Spain Universidad Francisco de Vitoria Madrid 28223Spain

BACKGROUND The prognostic value of the Systemic Inflammation Response Index(SIRI)in advanced pancreatic cancer is recognized,but its correlation with patients´nutritional status and outcomes remains unexplored.AIM To study the prognostic significance of SIRI and weight loss in metastatic pancreatic cancer.METHODS The PANTHEIA-Spanish Society of medical oncology(SEOM)study is a multicentric(16 Spanish hospitals),observational,longitudinal,non-interventional initiative,promoted by the SEOM Real World-Evidence work group.This pilot study sought to analyze the association between weight loss and inflammatory status as defined by SIRI.The cohort stems from a proof-of-concept pilot study conducted at one of the coordinating centers.Patients with pathologically confirmed metastatic pancreatic adenocarcinoma,treated from January 2020 to January 2023,were included.The index was calculated using the product of neutrophil and monocyte counts,divided by lymphocyte counts,obtained within 15 days before initiation chemotherapy.This study evaluated associations between overall survival(OS),SIRI and weight loss.RESULTS A total of 50 patients were included.66%of these patients were male and the median age was 66 years.Metastasis sites:36%liver,12%peritoneal carcinomatosis,10%lung,and 42%multiple locations.Regarding the first line palliative chemotherapy treatments:50%received gemcitabine plus nab-paclitaxel;28%,modified fluorouracil,leucovorin,irinotecan and oxaliplatin,and 16%were administered gemcitabine.42%had a weight loss>5%in the three months(mo)preceding diagnosis.21 patients with a SIRI≥2.3×10^(3)/L exhibited a trend towards a lower median OS compared to those with a SIRI5%weight loss before diagnosis,the median OS was 6 mo,in contrast to 19 mo for those who did not experience such weight loss(P=0.003).Patients with a weight loss>5%showed higher SIRI levels.This difference was statistically significant(P<0.000).For patients with a SIRI<2.3×10^(3)/L,those who did not

关键词： Pancreatic cancer Nutrition Prognostic factor Inflammation Advanced cancer Systemic inflammatory response index Weight loss

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Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase Ⅱ trial

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Cancer Biology & Medicine 2024年第5期21卷 433-444页

作者： Shuzhen Lai Peijing Li Xiaohui Liu Guihong Liu Tieming Xie Xing Zhang Xiaoxuan Wang Jing Huang Yiqiang Tang Zhigang Liu Guoping Shen Chaoming Li Fangxiao Lu Lei Wang Fagui Jiang Caixing Sun Yuanyuan Chen Ming Chen department of Radiotherapy Dongguan Institute of Clinical Cancer Research Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors Affiliated Dongguan Hospital Southern Medical University The Cancer Center The Fifth Affiliated Hospital of Sun Yat-Sen University department of Radiation oncology The First Affiliated Hospital of Sun Yat-Sen University department of oncology Maoming People's Hospital department of Radiation oncology Kecheng District People's Hospital Chinese Academy of Sciences department of Radiation oncology State Key Laboratory of Oncology in South China Sun Yat-sen University Cancer Center United Laboratory of Frontier Radiotherapy Technology of Sun Yat-sen University & Chinese Academy of Sciences Ion medical Technology Co. Ltd department of Radiation oncology The Second Affiliated Hospital of Soochow University department of Radiation oncology Yuebei People's Hospital Affiliated to the Medical College of Shantou University Chinese Academy of Sciences department of Radiation oncology The Second Clinical Medical College of Zhejiang Chinese Medical University department of Radiation oncology The Affiliated Hospital of Xuzhou Medical University Chinese Academy of Sciences State Key Laboratory of Translational Medicine and Innovative Drug Development Jiangsu Simcere Diagnostics Co. Ltd department of Radiation oncology The Affiliated Huai'an First People's Hospital of Nanjing Medical University department of Radiation oncology Jiangxi Cancer Hospital of Nanchang University

Objective: Glioblastomas are highly vascularized malignant tumors. We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor, anlotinib, for a newly diagnosed glioblastoma.Methods: This multicenter, single-arm trial（NCT04119674） enrolled 33 treatment-na?ve patients with histologically proven glioblastomas between March 2019 and November 2020. Patients underwent treatment with the standard STUPP regimen [fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w × 6 w（total = 54-60 Gy）] or radiotherapy plus continuous daily temozolomide（TMZ）(75 mg/m2of body surface area/d, 7 d/w from the first to the last day of radiotherapy), followed by 6 cycles of adjuvant TMZ（150±200 mg/m2× 5 d during each 28-d cycle） plus anlotinib(8 mg/d on d 1±14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy, 8 maximal cycles as adjuvant therapy, followed by maintenance at 8 mg/d. The primary endpoint was progression-free survival（PFS）. Secondary endpoints included overall survival（OS） and adverse events（AEs）.Results: Thirty-three patients received the planned treatment. The median PFS was 10.9 months（95% CI, 9.9±18.7 months） and the 12-month PFS rate was 48.5%. The median OS was 17.4 months（95% CI, 14.5±21.1 months） and the 12-month OS rate was 81.8%. The most common AEs included hypertriglyceridemia [58%（n = 19）], hypoalbuminemia [46%（n = 15）], and hypercholesterolemia [46%（n = 15）] during concurrent chemoradiotherapy and leukopenia [73%（n = 24）], hypertriglyceridemia [67%（n = 22）], and neutropenia [52%（n = 17）] during adjuvant therapy. Five patients discontinued treatment due to AEs. HEG1（HR, 5.6; 95% CI, 1.3±23.7; P = 0.021） and RP1L1 alterations（HR, 11.1; 95% CI, 2.2±57.2; P = 0.004） were associated with a significantly shorter PFS.Conclusions: Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity. HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

关键词： Glioblastoma anlotinib anti-angiogenesis multi-kinase inhibitor progression-free survival temozolomide

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Application of exosomal miRNA mediated macrophage polarization in colorectal cancer:Current progress and challenges

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oncology Research 2024年第1期32卷 61-71页

作者： YUN ZHANG SHALING TANG YUBO GAO ZHONGTING LU YUAN YANG JING CHEN TAO LI department of oncology School of Clinical MedicineNingxia Medical UniversityYinchuanChina General Hospital of Ningxia medical University YinchuanChina School of Basic medical Sciences Ningxia Medical UniversityYinchuanChina department of Surgical oncology Tumor HospitalThe General Hospital of Ningxia Medical UniversityYinchuanChina

Colorectal cancer(CRC)is a major global health problem with high morbidity and mortality rates.Surgical resection is the main treatment for early-stage CRC,but detecting it early is challenging.Therefore,effective therapeutic targets for advanced patients are still lacking.Exosomes,tiny vesicles in body fluids,play a crucial role in tumor metastasis,immune regulation,and drug resistance.Interestingly,they can even serve as a biomarker for cancer diagnosis and prognosis.Studies have shown that exosomes can carry miRNA,mediate the polarization of M1/M2 macrophages,promote the proliferation and metastasis of cancer cells,and affect the prognosis of CRC.Since the gastrointestinal tract has many macrophages,understanding the mechanism behind exosomal miRNA-mediated macrophage polarization in CRC treatment is crucial.This article summarizes recent advancements in the study of exosomal miRNAs in CRC and their potential as diagnostic and prognostic markers.

关键词： Colorectal cancer Exosomes microRNA Macrophages Treatment

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