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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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Can we triumph over locally advanced cervical cancer with colossal para-aortic lymph nodes? A case report

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World Journal of Clinical Cases 2024年第10期12卷 1851-1856页

作者： Abdulla Alzibdeh Issa Mohamad Lina Wahbeh Ramiz Abuhijlih Fawzi Abuhijla department of radiation oncology King Hussein Cancer CenterAmman 11941Jordan

BACKGROUND Para-aortic lymph nodes(PALNs)are common sites for the regional spread of cervical squamous cell carcinoma(SCC).CASE SUMMARY We report the case of a 36-year-old woman who presented with cervical SCC with multiple bulky PALNs,largest measured 4.5 cm×5 cm×10 cm.The patient was treated with radical intent with definitive chemoradiation using sequential doseescalated adaptive radiotherapy,followed by maintenance chemotherapy.The patient achieved a complete response;she has been doing well since the completion of treatment with no evidence of the disease for 2 years.CONCLUSION Regardless of the size of PALN metastases of cervical carcinoma origin,it is still treatable(with radical intent)via concurrent chemoradiation.Adaptive radiotherapy allows dose escalation with minimal toxicity.

关键词： Cervical cancer Bulky Lymph node Radiotherapy Para-aortic Case report

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Stereotactic body radiotherapy in pancreatic adenocarcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 14-19页

作者： Carolina de la Pinta radiation oncology department Ramón y Cajal University HospitalIRYCISAlcaláUniversity28034 MadridSpain

Background:Stereotactic body radiotherapy(SBRT)in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding tissue.This review aimed at the SBRT application in the treatment of pancreatic cancer.Data sources:We retrieved articles published in MEDLINE/PubMed from January 2017 to December 2022.Keywords used in the search included:“pancreatic adenocarcinoma”OR“pancreatic cancer”AND“stereotactic ablative radiotherapy(SABR)”OR“stereotactic body radiotherapy(SBRT)”OR“chemoradiotherapy(CRT)”.English language articles with information on technical characteristics,doses and fractionation,indications,recurrence patterns,local control and toxicities of SBRT in pancreatic tumors were included.All articles were assessed for validity and relevant content.Results:Optimal doses and fractionation have not yet been defined.However,SBRT could be the standard treatment in patients with pancreatic adenocarcinoma in addition to CRT.Furthermore,the combination of SBRT with chemotherapy may have additive or synergic effect on pancreatic adenocarcinoma.Conclusions:SBRT is an effective modality for patients with pancreatic cancer,supported by clinical practice guidelines as it has demonstrated good tolerance and good disease control.SBRT opens a possibility of improving outcomes for these patients,both in neoadjuvant treatment and with radical intent.

关键词： Chemoradiotherapy Pancreatic adenocarcinoma Radiotherapy Stereotactic body radiotherapy Stereotactic ablative radiotherapy

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Association of previously irradiated stable brain metastases with outcomes of atezolizumab-treated non-small cell lung cancer: A pooled analysis of individual patient data from three randomized trials

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Cancer Communications 2024年第2期44卷 278-281页

作者： Tiantian Guo Yue Zhou Fei Liang Zezhou Wang Vincent Bourbonne Lukas Käsmann Nora Sundahl Abraham Jing-Ching Wu Jianjiao Ni Zhengfei Zhu department of radiation oncology Fudan University Shanghai Cancer CenterShanghaiP.R.China department of oncology Shanghai Medical CollegeFudan UniversityShanghaiP.R.China Shanghai Clinical Research Center for radiation oncology ShanghaiP.R.China Shanghai Key Laboratory of radiation oncology ShanghaiP.R.China department of Biostatistics Zhongshan HospitalFudan UniversityShanghaiP.R.China department of Cancer Prevention Fudan University Shanghai Cancer CenterShanghaiP.R.China radiation oncology department University HospitalBrestFrance department of radiation oncology University HospitalLMU MunichMunichGermany department of radiation oncology AZ GroeningeKortrijkBelgium department of radiation oncology Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUSA Institute of Thoracic oncology Fudan UniversityShanghaiP.R.China

Dear Editor:Brain metastasis(BM)has long been recognized as a prognostic factor associated with poor prognosis for non-small cell lung cancer(NSCLC)in the era of con-ventional chemotherapy and targeted therapy[1].In the era of immunotherapy,controversial findings have been reported regarding the prognostic significance of BM in patients with NSCLC treated with programmed death-1/programmed death-ligand 1(PD-1/PD-L1)inhibitors.

关键词： chemotherapy NSCLC metastasis death

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Hemostatic radiotherapy for bleeding gastrointestinal

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World Journal of Gastrointestinal oncology 2024年第5期16卷 2261-2263页

作者： Vrushab Rao Soumya Singh Bhooshan Zade department of Cyberknife Radiosurgery and radiation oncology Ruby Hall ClinicPune 411001MaharashtraIndia

Hemostatic radiotherapy is a non-invasive treatment for bleeding gastrointestinal(GI)tumors,promoting tumor shrinkage,blood supply reduction,and fibrotic tissue formation.It is effective in cases where traditional interventions are insufficient or contraindicated and can prevent recurrent bleeding in patients with GI bleeding histories.Hypofractionation schedules are also effective for tumor control and patient compliance.

关键词： Gastrointestinal tumors Hemostatic radiotherapy Palliative radiotherapy Acute bleeding Hypofractionation

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Prediction of pathological complete response and prognosis in locally advanced rectal cancer

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World Journal of Gastrointestinal oncology 2024年第6期16卷 2520-2530页

作者： Yi-Jun Xu Dan Tao Song-Bing Qin Xiao-Yan Xu Kai-Wen Yang Zhong-Xu Xing Ju-Ying Zhou Yang Jiao Li-Li Wang department of radiation oncology The First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina department of radiation oncology The Fourth Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina School of radiation Medicine and Protection Medical College of Soochow UniversitySuzhou 215123Jiangsu ProvinceChina

BACKGROUND Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide.Neoadjuvant chemoradiotherapy(nCRT)is standard for locally advanced rectal cancer(LARC).Except for pathological examination after resection,it is not known exactly whether LARC patients have achieved pathological complete response(pCR)before surgery.To date,there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes.AIM To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC.METHODS Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed.Patients were categorized into pCR and non-pCR groups.Univariate analysis(using the χ^(2) test or Fisher’s exact test)and logistic multivariate regression analysis were used to study clinical predictors affecting pCR.The 5-year disease-free survival(DFS)and overall survival(OS)rates were calculated using Kaplan-Meier analysis,and differences in survival curves were assessed with the log-rank test.RESULTS Univariate analysis showed that pretreatment carcinoembryonic antigen(CEA)level,lymphocyte-monocyte ratio(LMR),time interval between neoadjuvant therapy completion and total mesorectal excision,and tumor size were correlated with pCR.Multivariate results showed that CEA≤5 ng/mL(P=0.039),LMR>2.73(P=0.023),and time interval>10 wk(P=0.039)were independent predictors for pCR.Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates(94.7%vs 59.7%,P=0.002)and 5-year OS rates(95.8%vs 80.1%,P=0.019)compared to the non-pCR group.Tumor deposits(TDs)were significantly correlated with shorter DFS(P=0.002)and OS(P<0.001).CONCLUSION Pretreatment CEA,LMR,and time interval contribute to predicting nCRT efficacy in LARC patients.Achieving pCR demonstrates longer DFS and OS.TDs correlate with poor prognosis.

关键词： Locally advanced rectal cancer Neoadjuvant chemoradiotherapy Pathological complete response Carcinoembryonic antigen Inflammation-related markers Tumor deposit Prognosis

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Microbiota in colorectal cancer related to liver metastasis

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Chinese Journal of Cancer Research 2024年第1期36卷 17-24页

作者： Peijun Wei Weiming Han Zitong Zhang Xue Tian Chen Yang Qiaoxuan Wang Weihao Xie Ying Liu Yuanhong Gao Hui Chang department of radiation oncology State Key Laboratory of Oncology in South ChinaGuangzhou 510060China Guangdong Provincial Clinical Research Center for Cancer Guangzhou 510060China Sun Yat-sen University Cancer Center Guangzhou 510060China department of Pediatric oncology State Key Laboratory of Oncology in South ChinaGuangzhou 510060China

The prevalence of colorectal cancer(CRC) is increasing annually and metastasis is the principal cause of death in patients with CRC, with the liver being the most frequently affected site. Many studies have shown a strong interplay between the gut flora, particularly Fusobacterium nucleatum(F. nucleatum), Escherichia coli, and Bacteroides fragilis, and the development of gut tumors. Some strains can induce gut inflammation and produce toxins that directly harm gut epithelial cells, ultimately accelerating the onset and progression of CRC. However,little clinical evidence exists on the specific interplay between the gut microflora and colorectal cancer liver metastasis(CRLM). Some research showed the existence of viable F. nucleatum in distant metastasis of CRC.Subsequently, gut microbiota products, such as lipopolysaccharides, sodium butyrate, and protein cathepsin K, were also found to affect the development of CRC. This article summarizes the mechanism and research status of the interplay between gut microflora and CRLM, discusses the importance of gut microflora in the treatment of CRLM, and proposes a new approach to understanding the mechanism of CRLM and potential treatments for the microbiome. It is anticipated that the gut microbiota will be a formidable therapeutic and prophylactic tool for treating and preventing CRLM.

关键词： Gut microbiota liver metastasis colorectal cancer

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Nicotinamide adenine dinucleotide phosphate oxidase in pancreatic diseases:Mechanisms and future perspectives

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World Journal of Gastroenterology 2024年第5期30卷 429-439页

作者： Ya-Wei Bi Long-Song Li Nan Ru Bo Zhang Xiao Lei department of Gastroenterology The First Medical Center of Chinese PLA General HospitalBeijing 100853China department of radiation oncology Chinese PLA General HospitalBeijing 100853China

Pancreatitis and pancreatic cancer(PC)stand as the most worrisome ailments affecting the pancreas.Researchers have dedicated efforts to unraveling the mechanisms underlying these diseases,yet their true nature continues to elude their grasp.Within this realm,oxidative stress is often believed to play a causal and contributory role in the development of pancreatitis and PC.Excessive accumulation of reactive oxygen species(ROS)can cause oxidative stress,and the key enzyme responsible for inducing ROS production in cells is nicotinamide adenine dinucleotide phosphate hydrogen oxides(NOX).NOX contribute to pancreatic fibrosis and inflammation by generating ROS that injure acinar cells,activate pancreatic stellate cells,and mediate macrophage polarization.Excessive ROS production occurs during malignant transformation and pancreatic carcinogenesis,creating an oxidative microenvironment that can cause abnormal apoptosis,epithelial to mesenchymal transition and genomic instability.Therefore,understanding the role of NOX in pancreatic diseases contributes to a more in-depth exploration of the exact pathogenesis of these diseases.In this review,we aim to summarize the potential roles of NOX and its mechanism in pancreatic disorders,aiming to provide novel insights into understanding the mechanisms underlying these diseases.

关键词： Nicotinamide adenine dinucleotide phosphate hydrogen oxides Pancreatitis Pancreatic cancer Reactive oxygen species Mechanism

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Management of lateral pelvic lymph nodes in rectal cancer:Is it time to reach an Agreement?

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World Journal of Clinical oncology 2024年第4期15卷 472-477页

作者： Sigfredo E Romero-Zoghbi Fernando López-Campos Felipe Couñago department of radiation oncology GenesisCareTalavera de la Reina 45600ToledoSpain department of radiation oncology Hospital Universitario Ramón Y CajalMadrid 28034Spain department of radiation oncology GenesisCare-Hospital Universitario Vithas Madrid La MilagrosaMadrid 28010Spain

In this editorial,we proceed to comment on the article by Chua et al,addressing the management of metastatic lateral pelvic lymph nodes(mLLN)in stage II/III rectal cancer patients below the peritoneal reflection.The treatment of this nodal area sparks significant controversy due to the strategic differences followed by Eastern and Western physicians,albeit with a higher degree of convergence in recent years.The dissection of lateral pelvic lymph nodes without neoadjuvant therapy is a standard practice in Eastern countries.In contrast,in the West,preference leans towards opting for neoadjuvant therapy with chemoradiotherapy or radiotherapy,that would cover the treatment of this area without the need to add the dissection of these nodes to the total mesorectal excision.In the presence of high-risk nodal characteristics for mLLN related to radiological imaging and lack of response to neoadjuvant therapy,the risk of lateral local recurrence increases,suggesting the appropriate selection of strategies to reduce the risk of recurrence in each patient profile.Despite the heterogeneous and retrospective nature of studies addressing this area,an international consensus is necessary to approach this clinical scenario uniformly.

关键词： Rectal cancer Lateral pelvic lymph node metastases Pelvic lymph node dissection Total neoadjuvant therapy Selective management of the lateral pelvic nodes Prophylactic management of the lateral pelvic nodes Chemoradiotherapy Total mesorectal excision

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Prognostic factors of breast cancer brain metastasis

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World Journal of Clinical oncology 2024年第1期15卷 5-8页

作者： Melek Yakar Durmuş Etiz department of radiation oncology Osmangazi UniversityEskişehir 26040Turkey department of radiation oncology Eskisehir Osmangazi University Faculty of MedicineEskişehir 26040Turkey

In this editorial we comment on the article by Chen et al published in the recent issue of the World Journal of Clinical oncology.Brain metastasis is one of the most serious complications of breast cancer and causes high morbidity and mortality.Brain metastases may involve the brain parenchyma and/or leptomeninges.Symptomatic brain metastases develop in 10%-16%of newly recognized cases each year,and this rate increases to 30%in autopsy series.Depending on the size of the metastatic foci,it may be accompanied by extensive vasogenic edema or may occur as small tumor foci.Since brain metastases are a significant cause of morbidity and mortality,early diagnosis can have significant effects on survival and quality of life.The risk of developing brain metastases emerges progressively due to various patient and tumor characteristics.Patient variability may be particularly important in the susceptibility and distribution of brain metastases because malignant blood must cross the brain barrier and move within the brain parenchyma.Some characteristics of the tumor,such as gene expression,may increase the risk of brain metastasis.Clinical growth,tumor stage,tumor grade,growth receptor positivity,HER2 positivity,molecular subtype(such as triple negative status,luminal/nonluminal feature)increase the risk of developing breast cancer metastasis.Factors related to survival due to breast cancer brain metastasis include both tumor/patient characteristics and treatment characteristics,such as patient age,lung metastasis,surgery for brain metastasis,and HER2 positivity.If cases with a high risk of developing brain metastasis can be identified with the help of clinical procedures and artificial intelligence,survival and quality of life can be increased with early diagnosis and treatment.At the same time,it is important to predict the formation of this group in order to develop new treatment methods in cases with low survival expectancy with brain metastases.

关键词： Breast cancer Brain metastasis Prognosis Artificial intelligence Clinicopathological features

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