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      Risk Classification for Overall Survival by the Neutrophil–Lymphocyte Ratio and the Number of Metastatic Sites in Patients Treated with Pembrolizumab—A Multicenter Collaborative Study in Japan

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          Abstract

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          Pembrolizumab improves overall survival (OS) in patients with platinum-refractory metastatic urothelial carcinoma (mUC), whereas objective response was observed in a modest number of patients (<25%) for this treatment, implying the distinct survival outcomes for those patients. Thus, the optimal risk stratification to predict survival outcomes at the initiation of pembrolizumab treatment would be helpful for physicians. In the present study, we examined a risk model developed using two clinical factors, including the number of metastatic sites and neutrophil–lymphocyte ratio (NLR), for predicting OS at the initiation of pembrolizumab treatment. This risk stratification seemed to be well-balanced (26.5%, 44.3%, and 29.2% in the favorable-risk, intermediate-risk, and poor-risk groups, respectively), and Kaplan–Meier curves illustrated clear discrimination of OS among the risk groups. Since the model proposed in the present study can be concisely determined at the initiation of pembrolizumab treatment, physicians may be encouraged to consider the risk group for daily practice.

          Abstract

          Pembrolizumab has emerged as the new standard of care in patients with platinum-refractory metastatic urothelial carcinoma (mUC), whereas the optimal risk stratification to predict survival outcomes is still controversial. We examined a risk model for overall survival (OS) in mUC treated with pembrolizumab using our multi-institutional dataset (212 patients). The median age was 72 years old. Median OS from the initiation of pembrolizumab treatment was 11.7 months. The objective response rate (ORR) was 26.4%. On multivariate analysis, multiple metastatic sites and an NLR > 3.50 at the initiation of pembrolizumab treatment were identified as independent predictors for OS. We next developed a risk model using those two predictors. Patients without any factors were assigned to the favorable-risk group (26.5%). Patients with either factor and both factors were assigned to the intermediate-risk group (44.3%), and poor-risk group (29.2%), respectively. Kaplan–Meier curves showed clear discrimination of OS among the risk groups ( p < 0.001). The ORR in each group was 35.7% in the favorable-risk group, 27.7% in the intermediate-risk group, and 17.7% in the poor-risk group. Given that the model can be concisely determined at the initiation of pembrolizumab treatment, physicians may be encouraged to consider the risk group for daily practice.

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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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            Index for rating diagnostic tests

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              Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma

              New England Journal of Medicine, 376(11), 1015-1026
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                15 July 2021
                July 2021
                : 13
                : 14
                : 3554
                Affiliations
                [1 ]Department of Urology, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan; taizo.uchimoto@ 123456ompu.ac.jp (T.U.); uro089@ 123456osaka-med.ac.jp (Y.Y.); kazuki.nishimura@ 123456ompu.ac.jp (K.N.); keita.nakamori@ 123456ompu.ac.jp (K.N.); uro072@ 123456osaka-med.ac.jp (Y.F.); uro065@ 123456osaka-med.ac.jp (T.M.); uro070@ 123456osaka-med.ac.jp (T.T.); uro061@ 123456osaka-med.ac.jp (T.T.); uro064@ 123456osaka-med.ac.jp (R.M.); uro066@ 123456osaka-med.ac.jp (Y.Y.); hirofumi.uehara@ 123456ompu.ac.jp (H.U.); uro052@ 123456osaka-med.ac.jp (H.H.); uro022@ 123456osaka-med.ac.jp (H.N.); tinamoto@ 123456osaka-med.ac.jp (T.I.); uro001@ 123456osaka-med.ac.jp (H.A.)
                [2 ]Translational Research Program, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan; sur144@ 123456osaka-med.ac.jp (K.T.); gyn123@ 123456osaka-med.ac.jp (T.T.)
                [3 ]Department of Urology, The Jikei University School of Medicine, Tokyo 105-8461, Japan; wfukuokaya@ 123456gmail.com (W.F.); h19ms-takahashi@ 123456jikei.ac.jp (K.T.); s-egpro@ 123456jikei.ac.jp (S.E.)
                [4 ]Department of Urology, Fujita-Health University School of Medicine, Nagoya 470-1192, Japan; takahara@ 123456fujita-hu.ac.jp
                Author notes
                [* ]Correspondence: kazumasa.komura@ 123456ompu.ac.jp (K.K.); tkimura0809@ 123456gmail.com (T.K.); Tel.: +81-726-83-1221 (K.K.); +81-33433-1111 (T.K.)
                Author information
                https://orcid.org/0000-0003-4157-1929
                https://orcid.org/0000-0002-5673-1553
                https://orcid.org/0000-0003-1559-1889
                https://orcid.org/0000-0003-0648-1370
                Article
                cancers-13-03554
                10.3390/cancers13143554
                8306968
                34298768
                f1b85c96-0991-41c1-9241-a298da4c91b3
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 16 June 2021
                : 13 July 2021
                Categories
                Article

                pembrolizumab,platinum-refractory,overall survival,risk model,risk factor,neutrophil-lymphocyte ratio,number of metastatic sites

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