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      Call for Papers: Digital Diagnostic Techniques

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      Recurrent, Tumor Mutation Burden-High, Cutaneous Angiosarcoma of the Scalp Treated with Pembrolizumab

      case-report

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Introduction

          Chemoradiotherapy with taxanes is well-recognized as a first-line therapy for cutaneous angiosarcoma (CAS), but second-line therapy for CAS is still controversial.

          Case Presentation

          In this report, we described a 75-year-old Japanese case of recurrent, tumor mutation burden-high CAS on the scalp treated with pembrolizumab. Our present case survived for 1 year despite of taxane refractory CAS with mediastinal lymph node metastasis, though the administration of anti-PD-1 Abs alone could not fully suppress the tumor progression of CAS.

          Conclusion

          Since various factors such as pro-angiogenic molecules are correlated with the tumor progression in CAS, the administration of anti-PD-1 Abs alone could not fully suppress the tumor progression of CAS. Further novel anticancer drugs are needed in the future for the treatment of CAS.

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          Most cited references10

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          Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic

          T A Chan, M. Yarchoan, E Jaffee … (2018)
          Abstract Background Treatment with immune checkpoint blockade (ICB) with agents such as anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), and/or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can result in impressive response rates and durable disease remission but only in a subset of patients with cancer. Expression of PD-L1 has demonstrated utility in selecting patients for response to ICB and has proven to be an important biomarker for patient selection. Tumor mutation burden (TMB) is emerging as a potential biomarker. However, refinement of interpretation and contextualization is required. Materials and methods In this review, we outline the evolution of TMB as a biomarker in oncology, delineate how TMB can be applied in the clinic, discuss current limitations as a diagnostic test, and highlight mechanistic insights unveiled by the study of TMB. We review available data to date studying TMB as a biomarker for response to ICB by tumor type, focusing on studies proposing a threshold for TMB as a predictive biomarker for ICB activity. Results High TMB consistently selects for benefit with ICB therapy. In lung, bladder and head and neck cancers, the current predictive TMB thresholds proposed approximate 200 non-synonymous somatic mutations by whole exome sequencing (WES). PD-L1 expression influences response to ICB in high TMB tumors with single agent PD-(L)1 antibodies; however, response may not be dependent on PD-L1 expression in the setting of anti-CTLA4 or anti-PD-1/CTLA-4 combination therapy. Disease-specific TMB thresholds for effective prediction of response in various other malignancies are not well established. Conclusions TMB, in concert with PD-L1 expression, has been demonstrated to be a useful biomarker for ICB selection across some cancer types; however, further prospective validation studies are required. TMB determination by selected targeted panels has been correlated with WES. Calibration and harmonization will be required for optimal utility and alignment across all platforms currently used internationally. Key challenges will need to be addressed before broader use in different tumor types.
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            Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study

            M Maio, P.A. Ascierto, L. Manzyuk … (2022)
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              Angiosarcoma patients treated with immune checkpoint inhibitors: a case series of seven patients from a single institution

              Vaia Florou, Andrew E. Rosenberg, Eric Wieder … (2019)
              Background Angiosarcoma is an uncommon endothelial malignancy and a highly aggressive soft tissue sarcoma. Due to its infiltrative nature, successful management of localized angiosarcoma is often challenging. Systemic chemotherapy is used in the metastatic setting and occasionally in patients with high-risk localized disease in neoadjuvant or adjuvant settings. However, responses tend to be short-lived and most patients succumb to metastatic disease. Novel therapies are needed for patients with angiosarcomas. Methods We performed a retrospective analysis of patients with locally advanced or metastatic angiosarcoma, who were treated with checkpoint inhibitors at our institution. We collected their clinical information and outcome measurements. In one patient with achieved complete response, we analyzed circulating and infiltrating T cells within peripheral blood and tumor tissue. Results We have treated seven angiosarcoma (AS) patients with checkpoint inhibitors either in the context of clinical trials or off label [Pembrolizumab + Axitinib (NCT02636725; n = 1), AGEN1884, a CTLA-4 inhibitor (NCT02694822; n = 2), Pembrolizumab (n = 4)]. Five patients had cutaneous angiosarcoma, one primary breast angiosarcoma and one radiation-associated breast angiosarcoma. At 12 weeks, 5/7 patients (71%) had partial response of their lesions either on imaging and/or clinical exam and two (29%) had progressive disease. 6/7 patients are alive to date and, thus far, 3/7 patients (43%) have progressed (median 3.4 months)- one achieved partial response after pembrolizumab was switched to ongoing Nivolumab/Ipilimumab, one died of progressive disease at 31 weeks (primary breast angiosarcoma) and one was placed on pazopanib. One patient had a complete response (CR) following extended treatment with monotherapy AGEN1884. No patient experienced any ≥ grade 2 toxicities. Conclusions This case series underscores the value of targeted immunotherapy in treating angiosarcoma. It also identifies genetic heterogeneity of cutaneous angiosarcomas and discusses specific genetic findings that may explain reported benefits from immunotherapy.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Case Rep Oncol
                Journal ID (iso-abbrev): Case Rep Oncol
                Journal ID (hwp): CRO
                Journal ID (publisher-id): CRO
                Title: Case Reports in Oncology
                Publisher: S. Karger AG (Basel, Switzerland )
                ISSN (Electronic): 1662-6575
                Publication date (Electronic): 28 November 2023
                Publication date Collection: Jan-Dec 2023
                Publication date PMC-release: 28 November 2023
                Volume: 16
                Issue: 1
                Pages: 1490-1493
                Affiliations
                [1]Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan
                Author notes
                Correspondence to: Taku Fujimura, tfujimura1@ 123456mac.com
                Article
                Publisher ID: 534657
                DOI: 10.1159/000534657
                PMC ID: 10684255
                PubMed ID: 38033417
                SO-VID: ca9ad66e-1af5-4a68-a7f8-0628532b3887
                Copyright © © 2023 The Author(s). Published by S. Karger AG, Basel
                License:

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC) ( http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

                History
                Date received : 20 September 2023
                Date accepted : 30 September 2023
                Date: 2023
                Page count
                Figures: 1, References: 10, Pages: 4
                Funding
                There is no funding source to declare for this study.
                Categories
                Subject: Case Report

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: recurrent cutaneous angiosarcoma,taxane resistant,foundation one liquid,tumor mutation burden,pembrolizumab
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: recurrent cutaneous angiosarcoma, taxane resistant, foundation one liquid, tumor mutation burden, pembrolizumab

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