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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="para0002" class="elsevierStylePara elsevierViewall">Malignant pleural mesothelioma &#40;MPM&#41; is a locally aggressive and invasive tumour with a median survival of 12 months&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> For the past few decades&#44; it has also been considered a highly lethal condition because of its recurrence despite standard approaches&#46; Currently&#44; there is no recommended therapy for relapsed MPM after chemotherapy or front-line treatment and disease control has been less than 30&#37; in all previous studies of second-line drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a> Advances in immunotherapy have been shifting the paradigm in the treatment of several advanced cancers and&#44; more recently&#44; its value in MPM has been investigated as a possible future therapeutic option&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a></p><p id="para0003" class="elsevierStylePara elsevierViewall">A sixty-two-year-old male&#44; active smoker&#44; with type-2 diabetes <span class="elsevierStyleItalic">mellitus</span>&#44; arterial hypertension&#44; and a history of prolonged occupational exposure to asbestos in the past had an incidental finding of unilateral complex and exudative pleural effusion associated with massive thickening of the costodiaphragmatic pleura&#46; Uniportal video-assisted thoracic surgery with pleural decortication was performed to manage complex pleural effusion and to collect samples that secured the pathological diagnosis&#46; Post-surgery study was complemented by positron emission tomography scanning &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1</a>&#41;&#44; clarifying the diagnosis of an unresectable epithelioid MPM&#44; with appearance of chest wall invasion&#46; The patient was initially submitted to pemetrexed &#40;500&#8239;mg&#47;m<span class="elsevierStyleSup">2</span>&#41; and carboplatin &#40;area under the concentration-time curve&#58; 5&#41;&#44; a less nephrotoxic regimen considering his comorbidities&#44; which was suspended after six treatment cycles due to disease progression&#44; deterioration in Eastern Cooperative Oncology Group &#40;ECOG&#41; performance status to 2 and development of left posterolateral thoracic mass&#44; painful on palpation&#44; needing antalgic radiotherapy &#40;total dose of 30&#8239;Gy in 10 fractions over 2 weeks&#41;&#46; Chest computed tomography &#40;CT&#41; scan also reported dimensional lesion increase and clear invasion of the chest wall &#40;<a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46; 2</a>A&#41;&#46; In this context&#44; anti-programmed cell death-1 &#40;PD-1&#41; monoclonal antibody immunotherapy was administered with single agent intravenous nivolumab 3&#8239;mg&#47;Kg&#44; every two weeks&#46; Initial outpatient reassessments were performed on a 14-day schedule&#46; It was possible to witness a progressive improvement in symptoms and weight recovery&#59; after seven weeks the chest-CT showed near complete remission of the neoplastic lesion &#40;<a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46; 2</a>B&#41;&#46; The thoracic painful mass became non-palpable at the end of the fourth nivolumab cycle&#46; Adverse events monitoring was performed before each treatment infusion&#46; He presented moderate arthralgia as a possible immune-related side-effect&#44; which was controlled with daily 5&#8239;mg prednisolone&#44; without interrupting therapy&#46; At the time this report was written&#44; the patient has been maintained on 3&#8239;mg&#47;Kg nivolumab infusions every two weeks&#44; with an excellent sustained therapeutic response &#40;<a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46; 2</a>C&#41; and significant improvement in quality of life &#40;current ECOG 1&#41;&#44; without unacceptable pharmacological toxicity&#44; maintaining benefits that came from immunotherapy throughout subsequent evaluations and well more than 24 months after diagnosis&#46;</p><elsevierMultimedia ident="fig0001"></elsevierMultimedia><elsevierMultimedia ident="fig0002"></elsevierMultimedia><p id="para0004" class="elsevierStylePara elsevierViewall">In fact&#44; epithelioid tumours account for 60&#37; of mesothelioma subtypes and have the best prognosis with more favourable response to chemotherapy than the other forms&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a> However&#44; this report demonstrates the progressive character of malignant mesothelioma despite standard chemotherapy and less aggressive histologic type&#46; Patient&#39;s declining status&#44; low response to second-line therapies and chemotherapy-related complications contributed towards the use of immunotherapy as an off-label rescue strategy&#46; This decision was also based on preliminary results from recent clinical trials that have suggested a potential role of anti-PD-1 monoclonal antibody in relapsed MPM&#44; namely nivolumab as a single drug&#44; with an acceptable safety profile&#44; which was important to improve our patient compliance and tolerance&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a> Positive outcomes were rapidly achieved and confirmed from the first control-CT&#44; maintaining a near-complete and sustained response ever since&#44; largely exceeding expected survival time for this malignancy&#44; with significant improvement in quality of life&#46; PD-ligand1 &#40;PD-L1&#41; expression has been reported in 40&#37; of mesothelioma overall&#44; with a higher rate in sarcomatoid histotype&#46;<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a> Nevertheless&#44; this case is representative of epithelioid subtype and&#44; although PD-L1 tumour proportion score has not been investigated&#44; the impressive obtained response with nivolumab might support a dependency of mesothelioma on this immunological checkpoint&#46;<a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a> As described in the literature&#44; tumour immune microenvironment plays a key role in MPM pathogenesis&#44; but to date&#44; efficacy of PD-L1 expression status as a predictive biomarker for the response to nivolumab may be limited&#59;<a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a> this is a critical area for more extensive studies&#46; Lastly&#44; immune checkpoint inhibitors are not without side-effects but&#44; in this case&#44; the potential benefit with nivolumab monotherapy outweighed the reported manageable adverse events&#46;</p><p id="para0005" class="elsevierStylePara elsevierViewall">We here present a case of epithelioid MPM which experienced a rapid disease progression after initial therapy but then had an exceptional and sustained response to single agent nivolumab&#46; It is an impressive shift in prognosis by a novel rescue strategy&#44; exceeding expected survival time and quality of life for this malignancy&#46; Therefore&#44; it highlights a promising role for this anti-PD-1 monoclonal antibody in future therapeutic options in those patients who have progressed after pemetrexed&#8211;platinum doublet chemotherapy&#46; This example should strongly encourage research for biomarkers to select optimal candidates for immunotherapy in terms of efficacy and tolerance&#46;</p><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0002">Patient consent</span><p id="para0006" class="elsevierStylePara elsevierViewall">Written informed consent was obtained from the patient for publication of his clinical details and images&#46;</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Funding</span><p id="para0007" class="elsevierStylePara elsevierViewall">No funding source&#46;</p></span></span>"
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Letter to the Editor
Relapsed malignant pleural mesothelioma: An impressive response to Nivolumab monotherapy
S. Costa-Martins
Corresponding author
sara.m.costamartins@gmail.com

Corresponding author.
, I. Vicente, S. Valente
Pulmonology Department, Centro Hospitalar Universitário Cova da Beira, Covilhã, Portugal
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="para0002" class="elsevierStylePara elsevierViewall">Malignant pleural mesothelioma &#40;MPM&#41; is a locally aggressive and invasive tumour with a median survival of 12 months&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> For the past few decades&#44; it has also been considered a highly lethal condition because of its recurrence despite standard approaches&#46; Currently&#44; there is no recommended therapy for relapsed MPM after chemotherapy or front-line treatment and disease control has been less than 30&#37; in all previous studies of second-line drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a> Advances in immunotherapy have been shifting the paradigm in the treatment of several advanced cancers and&#44; more recently&#44; its value in MPM has been investigated as a possible future therapeutic option&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a></p><p id="para0003" class="elsevierStylePara elsevierViewall">A sixty-two-year-old male&#44; active smoker&#44; with type-2 diabetes <span class="elsevierStyleItalic">mellitus</span>&#44; arterial hypertension&#44; and a history of prolonged occupational exposure to asbestos in the past had an incidental finding of unilateral complex and exudative pleural effusion associated with massive thickening of the costodiaphragmatic pleura&#46; Uniportal video-assisted thoracic surgery with pleural decortication was performed to manage complex pleural effusion and to collect samples that secured the pathological diagnosis&#46; Post-surgery study was complemented by positron emission tomography scanning &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1</a>&#41;&#44; clarifying the diagnosis of an unresectable epithelioid MPM&#44; with appearance of chest wall invasion&#46; The patient was initially submitted to pemetrexed &#40;500&#8239;mg&#47;m<span class="elsevierStyleSup">2</span>&#41; and carboplatin &#40;area under the concentration-time curve&#58; 5&#41;&#44; a less nephrotoxic regimen considering his comorbidities&#44; which was suspended after six treatment cycles due to disease progression&#44; deterioration in Eastern Cooperative Oncology Group &#40;ECOG&#41; performance status to 2 and development of left posterolateral thoracic mass&#44; painful on palpation&#44; needing antalgic radiotherapy &#40;total dose of 30&#8239;Gy in 10 fractions over 2 weeks&#41;&#46; Chest computed tomography &#40;CT&#41; scan also reported dimensional lesion increase and clear invasion of the chest wall &#40;<a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46; 2</a>A&#41;&#46; In this context&#44; anti-programmed cell death-1 &#40;PD-1&#41; monoclonal antibody immunotherapy was administered with single agent intravenous nivolumab 3&#8239;mg&#47;Kg&#44; every two weeks&#46; Initial outpatient reassessments were performed on a 14-day schedule&#46; It was possible to witness a progressive improvement in symptoms and weight recovery&#59; after seven weeks the chest-CT showed near complete remission of the neoplastic lesion &#40;<a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46; 2</a>B&#41;&#46; The thoracic painful mass became non-palpable at the end of the fourth nivolumab cycle&#46; Adverse events monitoring was performed before each treatment infusion&#46; He presented moderate arthralgia as a possible immune-related side-effect&#44; which was controlled with daily 5&#8239;mg prednisolone&#44; without interrupting therapy&#46; At the time this report was written&#44; the patient has been maintained on 3&#8239;mg&#47;Kg nivolumab infusions every two weeks&#44; with an excellent sustained therapeutic response &#40;<a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46; 2</a>C&#41; and significant improvement in quality of life &#40;current ECOG 1&#41;&#44; without unacceptable pharmacological toxicity&#44; maintaining benefits that came from immunotherapy throughout subsequent evaluations and well more than 24 months after diagnosis&#46;</p><elsevierMultimedia ident="fig0001"></elsevierMultimedia><elsevierMultimedia ident="fig0002"></elsevierMultimedia><p id="para0004" class="elsevierStylePara elsevierViewall">In fact&#44; epithelioid tumours account for 60&#37; of mesothelioma subtypes and have the best prognosis with more favourable response to chemotherapy than the other forms&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a> However&#44; this report demonstrates the progressive character of malignant mesothelioma despite standard chemotherapy and less aggressive histologic type&#46; Patient&#39;s declining status&#44; low response to second-line therapies and chemotherapy-related complications contributed towards the use of immunotherapy as an off-label rescue strategy&#46; This decision was also based on preliminary results from recent clinical trials that have suggested a potential role of anti-PD-1 monoclonal antibody in relapsed MPM&#44; namely nivolumab as a single drug&#44; with an acceptable safety profile&#44; which was important to improve our patient compliance and tolerance&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a> Positive outcomes were rapidly achieved and confirmed from the first control-CT&#44; maintaining a near-complete and sustained response ever since&#44; largely exceeding expected survival time for this malignancy&#44; with significant improvement in quality of life&#46; PD-ligand1 &#40;PD-L1&#41; expression has been reported in 40&#37; of mesothelioma overall&#44; with a higher rate in sarcomatoid histotype&#46;<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a> Nevertheless&#44; this case is representative of epithelioid subtype and&#44; although PD-L1 tumour proportion score has not been investigated&#44; the impressive obtained response with nivolumab might support a dependency of mesothelioma on this immunological checkpoint&#46;<a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a> As described in the literature&#44; tumour immune microenvironment plays a key role in MPM pathogenesis&#44; but to date&#44; efficacy of PD-L1 expression status as a predictive biomarker for the response to nivolumab may be limited&#59;<a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a> this is a critical area for more extensive studies&#46; Lastly&#44; immune checkpoint inhibitors are not without side-effects but&#44; in this case&#44; the potential benefit with nivolumab monotherapy outweighed the reported manageable adverse events&#46;</p><p id="para0005" class="elsevierStylePara elsevierViewall">We here present a case of epithelioid MPM which experienced a rapid disease progression after initial therapy but then had an exceptional and sustained response to single agent nivolumab&#46; It is an impressive shift in prognosis by a novel rescue strategy&#44; exceeding expected survival time and quality of life for this malignancy&#46; Therefore&#44; it highlights a promising role for this anti-PD-1 monoclonal antibody in future therapeutic options in those patients who have progressed after pemetrexed&#8211;platinum doublet chemotherapy&#46; This example should strongly encourage research for biomarkers to select optimal candidates for immunotherapy in terms of efficacy and tolerance&#46;</p><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0002">Patient consent</span><p id="para0006" class="elsevierStylePara elsevierViewall">Written informed consent was obtained from the patient for publication of his clinical details and images&#46;</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Funding</span><p id="para0007" class="elsevierStylePara elsevierViewall">No funding source&#46;</p></span></span>"
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Article information
ISSN: 25310437
Original language: English
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