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      Case series of pleomorphic carcinomas of the lung treated with nivolumab

      case-report

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          Abstract

          Pleomorphic carcinoma (PC) of the lung is a rare type of non‐small cell lung cancer, exhibiting aggressive behavior and resistance to chemotherapy and radiotherapy. A previous study reported that PCs expressed high levels of PD‐L1, suggesting the potential efficacy of immune checkpoint inhibitors in these tumors. We retrospectively reviewed the clinical records of three patients with PC of the lung treated with nivolumab: a 59‐year‐old woman (Case 1), a 66‐year‐old man (Case 2), and an 83‐year‐old man (Case 3). PD‐L1 was highly expressed in their tumor cells. Two cases showed a partial response with long progression‐free survival. However, in Case 2, brain and bone metastases progressed during nivolumab treatment in spite of high PD‐L1 expression. This case series indicates that nivolumab is effective to some extent for PC of the lung. However, the clinical course of patients treated with nivolumab should be carefully observed, even when PD‐L1 is highly expressed.

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          Most cited references7

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          The blockade of immune checkpoints in cancer immunotherapy.

          Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
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            Pleomorphic (spindle/giant cell) carcinoma of the lung. A clinicopathologic correlation of 78 cases.

            The authors undertook this study to define the clinical and histologic characteristics of spindle and giant cell carcinomas of the lung and the survival and prognostic features of these tumors. Seventy-eight cases of pleomorphic (spindle and/or giant cell) carcinoma of the lung were studied by light microscopy and immunohistochemistry to establish clinical, gross, and histologic parameters. Follow-up information was obtained from contributing physicians and analyzed by statistical means to determine prognostically significant parameters. The patient population consisted of 57 men and 21 women (male to female ratio, 2.7 to 1) between the ages of 35 and 83 years (mean, 62 years). Clinically, 58 patients (80%) presented with symptoms including thoracic pain, cough, and hemoptysis, whereas 14 (18%) were asymptomatic. At the time of diagnosis, 41% of the patients had clinical Stage I lesions, 6% Stage II lesions, 39% Stage III lesions, and 12% Stage IV lesions. Histologically, foci of squamous cell carcinoma were present in 8% of the tumors, large cell carcinoma in 25%, and adenocarcinoma in 45%. The remaining 22% of neoplasms were completely spindle and/or giant cell carcinomas. Spindle and giant cell carcinomas were found together in 38% of the patients. In the 69 patients for whom follow-up information was obtained, 53 (77%) died within 7 days to 6 years after diagnosis, with a 23-month mean survival (median, 10 months) (Kaplan-Meier method). There was a significant shortening of survival for patients with tumor size greater than 5 cm, clinical stage greater than 1, and lymph node involvement. The presence of nodal metastases was the most significant single prognostic factor, whereas the presence of squamous or adenocarcinomatous differentiation did not have an impact on length of survival. The frequency with which spindle and giant cell carcinomas are found together, their frequent association with other histologic subtypes of lung carcinoma, and the similar clinicopathologic features of these tumors suggest that they are best regarded as one type of lung cancer called pleomorphic carcinoma.
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              Characteristics and Prognostic Analysis of 69 Patients With Pulmonary Sarcomatoid Carcinoma.

              Pulmonary sarcomatoid carcinoma (PSC) is a rare malignancy.
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                Author and article information

                Contributors
                kanamasa@toneyama.go.jp
                Journal
                Thorac Cancer
                Thorac Cancer
                10.1111/(ISSN)1759-7714
                TCA
                Thoracic Cancer
                John Wiley & Sons Australia, Ltd (Melbourne )
                1759-7706
                1759-7714
                07 September 2017
                November 2017
                : 8
                : 6 ( doiID: 10.1111/tca.2017.8.issue-6 )
                : 724-728
                Affiliations
                [ 1 ] Department of Thoracic Oncology National Hospital Organization Toneyama National Hospital Toyonaka Japan
                [ 2 ] Department of Laboratory Medicine and Pathology National Hospital Organization Toneyama National Hospital Toyonaka Japan
                Author notes
                [*] [* ] Correspondence

                Masaki Kanazu, Department of Thoracic Oncology, National Hospital Organization Toneyama National Hospital, 5‐1‐1 Toneyama, Toyonaka‐city, Osaka 560‐8552, Japan.

                Tel: +81 6 6853 2001

                Fax: +81 6 6853 3127

                Email: kanamasa@ 123456toneyama.go.jp

                Author information
                http://orcid.org/0000-0003-4405-1929
                Article
                TCA12505
                10.1111/1759-7714.12505
                5668504
                28881488
                f5c0f344-34e3-4d72-9bf7-14d5a9fdf816
                © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 30 June 2017
                : 08 August 2017
                : 09 August 2017
                Page count
                Figures: 3, Tables: 1, Pages: 5, Words: 2026
                Categories
                Case Report
                Case Reports
                Custom metadata
                2.0
                tca12505
                November 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.1 mode:remove_FC converted:03.11.2017

                immune checkpoint inhibitor,nivolumab,non‐small cell lung cancer,pleomorphic carcinoma,programmed death‐1 ligand

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