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Prolonged progression-free survival and overall survival are associated with diabetes mellitus but inversely associated with levels of blood glucose in patients with lung cancer

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Chinese Medical Journal 2020年第7期133卷 786-791页

作者： Ning-Fang Wang Hong-Mei Tang Fang-Lei Liu Qun-Ying Hong Department of Pulmonary Medicine Zhongshan HospitalFudan UniversityShanghai 200032China

Background:Previous studies have provided conflicting evidence about the increased overall survival(OS)in lung cancer patients with diabetes mellitus(DM)compared with those without DM.This study assessed progression-free survival(PFS)/OS in lung cancer patients with or without DM and tentatively analyzed the impact of blood glucose levels on PFS/OS in lung cancer patients.Methods:Data were collected from lung cancer patients based upon admission records from January 2010 to January 2012 and follow-up records from January 2010 to January 2015 in the Department of Pulmonary Medicine,Zhongshan Hospital,Fudan University,Shanghai.The data included patient sex,age,body mass index(BMI),smoking status,history of DM,level of blood glucose,pathological type,clinical stage of cancer,chemotherapy regimen,and history of anti-DM drugs.The Cox regression model and Kaplan-Meier method were used for the analysis of hazard factors and PFS/OS.For comparison of PFS/OS in lung cancer with or without DM,patients were divided into three groups:lung cancer with DM,lung cancer without DM but with elevated level of blood glucose,lung cancer without DM or elevated level of blood glucose.Results:In total,the data from 200 lung cancer patients(138 males/62 females,aged 29.0 to 78.0 years,mean 60.0±8.6 years)were collected.For the comparison of PFS/OS in lung cancer patients with or without DM,patients were divided into three groups:lung cancer with DM(n=31);lung cancer without DM but with elevated levels of blood glucose(n=40);and lung cancer without both DM and elevated levels of blood glucose(n=128),whereas 1 patient dropped out of the study.All the patients underwent complete chemotherapy and were followed up for 36.0 to 60.0 months.Kaplan-Meier survival analysis showed that lung cancer patients with DM had increased PFS and OS compared with those without DM(log-rank,P<0.05,P<0.01);the median PFS in lung cancer with DM was 12.0 months(95%confidence interval[CI],4.0-16.0)vs.6.0 months in those without DM(95%CI,5.8-6.3);and the median OS in

关键词： Diabetes mellitus Lung cancer Overall survival progression-free survival Serum glucose level

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Efficacy of bevacizumab-containing chemotherapy in metastatic colorectal cancer and CXCL5 expression: Six case reports

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World Journal of Gastroenterology 2020年第16期26卷 1979-1986页

作者： Apolonia Novillo María Gaibar Alicia Romero-Lorca María Fuencisla Gilsanz Laura Beltrán Miguel Galán Beatriz Antón Diego Malón Amalia Moreno Ana Fernández-Santander Department of Pre-clinical Dentistry Health Sciences FacultyUniversidad Europea de MadridVillaviciosa de OdónMadrid 28670Spain Department of Health Sciences Health Sciences FacultyUniversidad Europea de MadridVillaviciosa de OdónMadrid 28670Spain Department of Medicine Health Sciences FacultyUniversidad Europea de MadridVillaviciosa de OdónMadrid 28670Spain Department of Oncology University Hospital of FuenlabradaFuenlabradaMadrid 28942Spain Department of Pathological Anatomy University Hospital of FuenlabradaFuenlabradaMadrid 28942Spain

BACKGROUND In metastatic colorectal cancer(mCRC),the anti-vascular endothelial growth factor drug bevacizumab(BVZ)plus chemotherapy significantly improves progression-free survival compared to chemotherapy(CT)alone.This benefit is not,however,observed in all patients.While increased chemokine CXCL5 gene expression promoting angiogenesis has been proposed as a prognostic mCRC biomarker,few studies have examined its relationship with drug efficacy.This study sought to analyze tumor CXCL5 gene expression in six patients with different efficacy of BVZ-containing CT in terms of the tumor response to treatment.CASE SUMMARY We report six cases of stage IV KRAS-mutated mCRC.Patients were given first line treatment with BVZ-containing chemotherapy in University Hospital of Fuenlabrada.The six patients differed in terms of primary tumor location(right/left side),tumor burden(mostly hepatic and peritoneal disease)and clinical disease course.Before treatment onset,total RNA was isolated from paraffinated tumor biopsy specimens and CXCL5 gene expression quantified through conventional RT-qPCR procedures.Our main finding was that CXCL5 expression levels were several times higher in three patients with lower progression free survival(under 6 mo)from the start of treatment.CONCLUSION A higher expression of CXCL5 was observed in the three patients showing worse tumor response to treatment.

关键词： Colorectal cancer Bevacizumab Chemokine CXCL5 Gene expression progression-free survival Case report

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Clinical significance and risk factors of postembolization fever in patients with hepatocellular carcinoma

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World Journal of Gastroenterology 2013年第2期19卷 284-289页

作者： Chung Hwan Jun Ho Seok Ki Hoon Ki Lee Kang Jin Park Seon Young Park Sung Bum Cho Chang Hwan Park Young Eun Joo Hyun Soo Kim Sung Kyu Choi Jong Sun Rew Division of Gastroenterology Department of Internal MedicineChonnam National University Medical SchoolGwangju 501-757South Korea

AIM:To investigate tumor response and survival in patients with postembolization fever(PEF) and to determine the risk factors for PEF.METHODS:Four hundred forty-three hepatocellular carcinoma(HCC) patients who underwent the first session of transcatheter arterial chemoembolization(TACE) between January 2005 and December 2009 were analyzed retrospectively.PEF was defined as a body temperature greater than 38.0 ℃ that developed within 3 d of TACE without evidence of infection.The tumor progression-free interval was defined as the interval from the first TACE to the second TACE based on mRECIST criteria.Clinical staging was based on the American Joint Committee on Cancer tumor,node,metastases(TNM) classification of malignant tumors.All patients were admitted before their 1 st TACE treatment,and blood samples were obtained from all patients before and after treatment.Clinicoradiological variables and host-related variables were compared between two groups:patients with PEF vs patients without PEF.Additionally,variables related to 20-mo mortality and tumor progression-free survival were analyzed.RESULTS:The study population comprised 370(85.4%) men and 73(14.6%) women with a mean age of 62.29 ± 10.35 years.A total of 1836 TACE sessions were conducted in 443 patients,and each patient received between 1 and 27(mean:4.14 ± 3.57) TACE sessions.The mean follow-up duration was 22.23 ± 19.6 mo(range:0-81 mo).PEF developed in 117 patients(26.41%) at the time of the first TACE session.PEF was not associated with 20-mo survival(P = 0.524) or computed tomography(CT) response(P = 0.413) in a univariate analysis.A univariate analysis further indicated that diffuse-type HCC(P = 0.021),large tumor size(≥ 5 cm)(P = 0.046),lipiodol dose(≥ 7 mL,P = 0.001),poor blood glucose control(P = 0.034),alanine aminotransferase(ALT) value after TACE(P = 0.004) and C-reactive protein(CRP) value after TACE(P = 0.036) served as possible risk factors correlated with PEF.The ALT value after TACE(P = 0.021) and lipiodol dose over 7 mL(P = 0.011) were i

关键词： Chemoembolization Therapeutic Fever Carcinoma Hepatocellular Prognosis progression-free survival

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Long lasting response to second-line everolimus in kidney cancer

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World Journal of Clinical Cases 2013年第5期1卷 166-168页

作者： Antonella Virtuoso Tania Policastro Michela Izzo Piera Federico Carlo Buonerba Pasquale Rescigno Giuseppe Di Lorenzo Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica Università degli Studi Federico Ⅱ80131 NaplesItaly Deparment of Clinical Medicine University Federico Ⅱ of Naples80131 Naples Italy

In the case presented here, everolimus was administered after first line therapy with sunitinib in a patient with metastatic renal cell carcinoma. The safety profile was excellent. The prolonged progression-free survival(PFS) obtained with everolimus in this case is of peculiar interest, as it is a multiple of the median PFS obtained in with everolimus in the regulatory trial. Such finding suggests that a subset of patients with renal cell carcinma may particularly benefit from everolimus.

关键词： Metastatic renal cell carcinoma Everolimus(RAD001) Sunitinib progression-free survival

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Absolute Lymphocyte/Monocyte Ratio at Diagnosis and Interim Positron-Emission Tomography Predict Survival in Classical Hodgkin Lymphoma

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Journal of Cancer Therapy 2013年第3期4卷 452-459页

作者： Luis F. Porrata Kay M. Ristow Thomas M. Habermann Thomas E. Witzig Joseph P. Colgan David J. Inwards Stephen M. Ansell Ivana N. Micallef Patrick B. Johnston Grzegorz Nowakowski Carrie A. Thompson Svetomir N. Markovic Division of Hematology Internal Medicine Mayo College of Medicine Rochester USA

Interim Positron-Emission Tomography (int-PET) and the peripheral blood absolute lymphocyte/monocyte ratio at di- agnosis (ALC/AMC-DX) have been shown to be predictors for progression-free survival (PFS) and time to progression (TTP) in classical Hodgkin lymphoma (cHL). Therefore, we studied if the combination of ALC/AMC-DX and the (int-PET) can further stratified PFS and TTP in cHL patients. Patients were required to be diagnosed, treated, and followed with int-PET at Mayo Clinic, Rochester, Minnesota. From 2000 until 2008, 111 cHL patients qualified for the study. The median follow-up was 2.8 years (range: 0.3 - 10.4 years). Patients with a negative int-PET (N = 98) pre- sented with a higher ALC/AMC-DX (median of 2.32, range: 0.26 - 37.5) compared with patients with a positive int-PET (N = 13) (median of 0.9, range: 0.29 - 3.10), p 1.1. Group 1 experienced superior PFS and TTP in comparison with the other groups. In conclusion, the combination of ALC/AMC-DX and the int-PET provides a simple model to assess clinical outcomes in cHL.

关键词： Classical Hodgkin Lymphoma Absolute Lymphocyte/Monocyte Ratio at Diagnosis Interim PET-Scan progression-free Survival Time to progression

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Systematic literature review of the antitumor effect of octreotide in neuroendocrine tumors

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World Journal of Meta-Analysis 2018年第2期6卷 9-20页

作者： Stephanie M Barrows Beilei Cai Catherine Copley-Merriman Kelly R Wright Colleen V Castro Raoudha Soufi-Mahjoubi RTI Health Solutions Novartis Pharmaceuticals RTI Health Solutions Research Triangle Park

AIM To provide a comprehensive examination of the existing evidence of the antitumor effect of long-acting octreotide in neuroendocrine tumors(NETs).METHODS A systematic literature review of clinical trials and observational studies was conducted in PubM ed, EMBASE, and Cochrane through January 18, 2017. Conference abstracts for 2015 and 2016 from 5 scientific meetings were also searched.RESULTS Of 41 articles/abstracts identified, 13 unique studies compared octreotide with active or no treatment. Two of the 13 studies were clinical trials; the remaining were observational studies. The phase 3 Placebo-Controlled, Double-Blind, Prospective, Randomized Study of the Effect of Octreotide long-acting repeatable(LAR) in the Control of Tumor Growth in Patients with MetastaticNeuroendocrine Midgut Tumors clinical trial showed that long-acting octreotide significantly prolonged time to tumor progression compared with placebo in patients with functionally active and inactive metastatic midgut NETs; no statistically significant difference in overall survival(OS) was observed, possibly due to the crossover of placebo patients to octreotide. Retrospective observational studies found that long-acting octreotide use was associated with significantly longer OS than no octreotide use for patients with distant metastases although not for those with local/regional disease. CONCLUSION The clinical trial and observational studies with informative evidence support long-acting octreotide's antitumor effect on time to tumor progression and OS. This review showed the rarity of existing studies assessing octreotide's antitumor effect and recommends that future research is warranted.

关键词： Neuroendocrine tumors Antitumor effect Octreotide Overall survival progression-free survival

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Maintaining clarity:Review of maintenance therapy in nonsmall cell lung cancer

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World Journal of Clinical Oncology 2014年第2期5卷 103-113页

作者： Kristen R Dearing Ashish Sangal Glen J Weiss Department of Clinical Research Cancer Treatment Centers of America Department of Medicine Cancer Treatment Centers of America CRAB-Clinical Trials Consortium

The purpose of this article is to review the role of maintenance therapy in the treatment of advanced nonsmall cell lung cancer(NSCLC). A brief overview about induction chemotherapy and its primary function in NSCLC is provided to address the basis of maintenance therapies foundation. The development of how maintenance therapy is utilized in this population is discussed and current guidelines for maintenance therapy are reviewed. Benefits and potential pitfalls of maintenance therapy are addressed, allowing a comprehensive review of the achieved clinical benefit that maintenance therapy may or may not have on NSCLC patient population. A review of current literature was conducted and a table is provided comparing the results of various maintenance therapy clinical trials. The table includes geographical location of each study, the number of patients enrolled, progression free survival and overall survival statistics, post-treatment regimens and if molecular testing was conducted. The role of molecular testing in relation to therapeutic treatment options foradvanced NSCLC patients is discussed. A treatment algorithm clearly depicts first line and second line treatment for management of NSCLC and includes molecular testing, maintenance therapy and the role clinical trials have in treatment of NSCLC. This treatment algorithm has been specifically tailored and developed to assist clinicians in the management of advanced NSCLC.

关键词： Maintenance therapy Clinical trials Nonsmall cell lung cancer Molecular aberrations progression-free survival Overall survival

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Efficacy of Long-Term Treatment with Low-Dose Thalidomide for Patients with Relapsed/Refractory Multiple Myeloma

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International Journal of Clinical Medicine 2011年第5期2卷 570-575页

作者： Kazuyuki Shimizu Hirokazu Murakami Morio Sawamura Yutaka Hattori Shin-ichiro Okamoto Akiyoshi Miwa Isamu Sugiura Chihiro Shimazaki Masafumi Taniwaki Tadao Ishida Toshiaki Hayashi Hiroshi Kosugi Masaaki Yuge Shinsuke Iida Takashi Ishida Kazutaka Sunami Hideki Asaoku Akira Sakai Masahiro Abe Toshiyuki Takagi 不详

Introduction: We report the results of a prospective study of long-tern treatment with single-agent thalidomide in patients who had responded in a preceding trial of the use of thalidomide for relapsed/refractory myeloma. Patients and Methods: Nineteen patients were enrolled: 11 patients (57.9%) treated at a dosage of 100 mg/day;2 patients (10.5%) at a dosage of 200 mg/day;2 patients (10.5%) at a dosage of 300 mg/day;and 4 patients (21.1%) at a dosage of 400 mg/day. The median follow-up from the start of the preceding study was 3.0 years. At the time of entry to this study, 5 patients (26.3%) had partial response (PR), another 5 patients (26.3%) had a minimal response (MR), and the remaining 9 patients (47.4%) had shown no change (NC). Results: The cumulative MR rate was 78.9% (at the 32nd week) and the cumulative PR rate was 47.4% (at the 112th week). The median progression-free survival was 104 weeks and the median time to next treatment was 144 weeks. No patients experienced grade 4 or greater hematologic toxicity or grade 3 or greater non-hematologic toxicity. Conclusion: Long-term thalidomide maintenance therapy induced an increase in response rate, suppressed the progression to active myeloma without severe adverse events, and contributed to long survival with good activities of daily living.

关键词： Maintenance Therapy progression-free Survival Time to Next Treatment Efficacy Safety

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End points of clinical trials in metastatic castration-resistant prostate cancer:A systematic review

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World Journal of Methodology 2014年第2期4卷 123-132页

作者： Giuseppe Colloca Antonella Venturino Ilaria Governato Division of Medical Oncology "Giovanni Borea" HospitalI-18038 SanremoItaly Division of Medical Oncology Santo Spirito Hospital00186 RomaItaly

AIM:To review the definition and performance of the commonly used end points in trials of systemic therapies in metastatic castration-resistant prostate cancer patients. METHODS: A literature search was undertaken on Pub Med database to identify studies meeting established criteria, with the aim of selecting randomized clinical trials and study definition and performance of their end points. The end points were grouped into three categories: overall survival(OS), time-to-event end points, and response end points. A special analysis was performed for secondary end points of the studies which documented a benefit in OS in the experimental arm. Finally, publishes analyses for surrogacy of the included end points were also reported.RESULTS: OS, time-to-event and response end points in 31 selected trials were analyzed. OS was the primary end point in 14 trials, and the secondary end point in 17. A time-to-event end point was the primaryend point in 8 studies, and the secondary end point in 22; the most reported time-to-event end points were composite end points, and the events changed among trials. A response end point was the primary end point in 9 studies, in 3 it was prostate-specific antigen(PSA)-related, in 3 pain-related and in 3 mixed. A response end point was the secondary end point in 19 studies: PSA response and radiologic response were the most frequently used secondary end points in 19 and 11 trials, respectively, while pain response was used in 5 studies.

关键词： Metastatic castration-resistant prostate cancer End points progression-free survival Prostate-specifc antigen Chemotherapy Palliative response

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