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      The safety and efficacy of first-line atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma: A multicenter real-world study from Turkey

      research-article
      , MD a , * , , , MD a , , MD b , , MD c , , MD d , , MD e , , MD f , , MD g , , MD h , , MD i , , MD j , , MD k , , MD l , , MD m , , MD n , , MD n , , MD o , , MD p , , MD q , , MD r , , MD s , , MD t , , MD t , , MD u , , MD n , , MD v , , MD w , , MD x , , MD x , , MD a , , MD w , , MD b , , MD r , , MD a
      Medicine
      Lippincott Williams & Wilkins
      atezolizumab, bevacizumab, hepatocellular carcinoma, immunotherapy

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          Abstract

          The aim of the study was to evaluate the real-world clinical outcomes of atezolizumab and bevacizumab (Atez/Bev) as the initial therapy for advanced hepatocellular carcinoma (HCC). We retrospectively analyzed 65 patients treated with Atez/Bev for advanced HCC from 22 institutions in Turkey between September 2020 and March 2023. Responses were evaluated by RECIST v1.1 criteria. The median progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan–Meier method. Cox regression model was employed to conduct multivariate analyses. The median age was 65 (range, 22–89) years, and 83.1% of the patients were male. A total of 1.5% achieved a complete response, 35.4% had a partial response, 36.9% had stable disease, and 26.2% had progressive disease. The disease control rate was 73.8% and associated with alpha-fetoprotein levels at diagnosis and concomitant antibiotic use. The incidence rates of any grade and grade ≥ 3 adverse events were 29.2% and 10.7%, respectively. At a median follow-up of 11.3 (3.4–33.3) months, the median PFS and OS were 5.1 (95% CI: 3–7.3) and 18.1 (95% CI: 6.2–29.9) months, respectively. In univariate analyses, ECOG-PS ≥ 1 (relative to 0), Child-Pugh class B (relative to A), neutrophil-to-lymphocyte ratio (NLR) > 2.9 (relative to ≤ 2.9), and concomitant antibiotic use significantly increased the overall risk of mortality. Multivariate analysis revealed that ECOG-PS ≥ 1 (HR: 2.69, P = .02), NLR > 2.9 (HR: 2.94, P = .017), and concomitant antibiotic use (HR: 4.18, P = .003) were independent predictors of OS. Atez/Bev is an effective and safe first-line therapy for advanced-stage HCC in a real-world setting. The survival benefit was especially promising in patients with a ECOG-PS score of 0, Child-Pugh class A, lower NLR, and patients who were not exposed to antibiotics during the treatment.

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).

            Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response) and disease progression are useful endpoints in clinical trials. Since RECIST was published in 2000, many investigators, cooperative groups, industry and government authorities have adopted these criteria in the assessment of treatment outcomes. However, a number of questions and issues have arisen which have led to the development of a revised RECIST guideline (version 1.1). Evidence for changes, summarised in separate papers in this special issue, has come from assessment of a large data warehouse (>6500 patients), simulation studies and literature reviews. HIGHLIGHTS OF REVISED RECIST 1.1: Major changes include: Number of lesions to be assessed: based on evidence from numerous trial databases merged into a data warehouse for analysis purposes, the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total (and from five to two per organ, maximum). Assessment of pathological lymph nodes is now incorporated: nodes with a short axis of 15 mm are considered measurable and assessable as target lesions. The short axis measurement should be included in the sum of lesions in calculation of tumour response. Nodes that shrink to <10mm short axis are considered normal. Confirmation of response is required for trials with response primary endpoint but is no longer required in randomised studies since the control arm serves as appropriate means of interpretation of data. Disease progression is clarified in several aspects: in addition to the previous definition of progression in target disease of 20% increase in sum, a 5mm absolute increase is now required as well to guard against over calling PD when the total sum is very small. Furthermore, there is guidance offered on what constitutes 'unequivocal progression' of non-measurable/non-target disease, a source of confusion in the original RECIST guideline. Finally, a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included. Imaging guidance: the revised RECIST includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions. A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI. It was concluded that, at present, there is not sufficient standardisation or evidence to abandon anatomical assessment of tumour burden. The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression. As is detailed in the final paper in this special issue, the use of these promising newer approaches requires appropriate clinical validation studies.
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              EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma

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                Author and article information

                Contributors
                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MD
                Medicine
                Lippincott Williams & Wilkins (Hagerstown, MD )
                0025-7974
                1536-5964
                10 November 2023
                10 November 2023
                : 102
                : 45
                : e35950
                Affiliations
                [a ] Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey
                [b ] Department of Medical Oncology, Ege University Faculty of Medicine, Izmir, Turkey
                [c ] Department of Internal Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkey
                [d ] Department of Medical Oncology, Erciyes University Faculty of Medicine, Kayseri, Turkey
                [e ] Department of Medical Oncology, Bozyaka Education and Research Hospital, Izmir, Turkey
                [f ] Department of Medical Oncology, Acibadem University Hospital, Istanbul, Turkey
                [g ] Department of Medical Oncology, Namik Kemal University, Tekirdag, Turkey
                [h ] Department of Medical Oncology, Anadolu Medical Center, Kocaeli, Turkey
                [i ] Department of Medical Oncology, Koc University Hospital, Istanbul, Turkey
                [j ] Department of Medical Oncology, Cukurova University Faculty of Medicine, Adana, Turkey
                [k ] Department of Medical Oncology, Marmara University School of Medicine, Istanbul, Turkey
                [l ] Department of Medical Oncology, Istinye University, Medical Park Goztepe Hospital, Istanbul, Turkey
                [m ] Department of Oncology, Kartal Lutfi Kirdar Teaching and Research Hospital, Istanbul, Turkey
                [n ] Department of Medical Oncology, Prof Dr. Cemil Tascioglu City Hospital, Istanbul, Turkey
                [o ] Department of Medical Oncology, Sakarya University Faculty of Medicine, Sakarya, Turkey
                [p ] Department of Medical Oncology, Gulhane School of Medicine, Ankara, Turkey
                [q ] Department of Medical Oncology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
                [r ] Department of Medical Oncology, Ankara City Hospital, Yildirim Beyazit University, Ankara, Turkey
                [s ] Department of Medical Oncology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey
                [t ] Department of Medical Oncology, Dokuz Eylül University Faculty of Medicine, Izmir, Turkey
                [u ] Department of Medical Oncology, Gayrettepe Florence Nightingale Hospital, Istanbul, Turkey
                [v ] Department of Medical Oncology, Izmir University of Economics Faculty of Medicine, Izmir, Turkey
                [w ] Department of Medical Oncology, Istanbul University Institute of Oncology, Istanbul, Turkey
                [x ] Department of Medical Oncology, Memorial Ankara Hospital, University of Uskudar, Ankara, Turkey.
                Author notes
                [* ]Correspondence: Arif Akyildiz, Hacettepe University Cancer Institute, Department of Medical Oncology, Sihhiye, Ankara 06100, Turkey (e-mail: drakyildizarif@ 123456gmail.com ).
                Author information
                https://orcid.org/0000-0002-4452-2076
                https://orcid.org/0000-0002-7093-2722
                Article
                00033
                10.1097/MD.0000000000035950
                10637501
                37960746
                901c964a-6124-47bf-b339-622a766352d4
                Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 August 2023
                : 13 September 2023
                : 13 October 2023
                Categories
                5700
                Research Article
                Observational Study
                Custom metadata
                TRUE

                atezolizumab,bevacizumab,hepatocellular carcinoma,immunotherapy

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