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The molecular study showed no mutations or molecular translocations &#40;EGFR&#44; KRAS&#44; BRAF&#44; ALK and ROS1-negative&#41;&#46; The patient received 2 cycles of cisplatin&#43;pemetrexed&#44; and her first follow-up CT performed 8 weeks later revealed the appearance of right inguinal lymphadenopathy and tumor-like pelvic masses located theoretically in the right uterine appendage and in the left paracolic gutter&#44; so second-line treatment with nivolumab began &#40;3<span class="elsevierStyleHsp" style=""></span>mg&#47;kg every 15 days&#41;&#46; Imaging studies performed at 8 weeks showed progression of the abdominopelvic and brain lesions&#44; and the patient&#39;s general condition had deteriorated &#40;ECOG 3&#41;&#44; so she was referred to the palliative care unit&#46; One year later&#44; she attended the clinic with improvement of her general condition &#40;ECOG 1&#41; and a CT performed for re-assessment revealed that the abdominopelvic lesions and the brain lesions seen on the head MRI had disappeared &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The patient is currently in complete radiological response after 41 months of follow-up&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">In recent years&#44; the therapeutic options for advanced non-small cell lung cancer have increased significantly&#46; This new therapeutic arsenal benefits some patients&#44; but has introduced some different forms of toxicity&#46; In this respect&#44; immunomodulatory drugs may lead to complications associated with the immune system&#44; with other comorbidities or treatments&#44; and even paradoxical responses&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">4</span></a> Pseudoprogression is a form of clinical response consisting of radiological worsening of the disease during treatment for an undetermined period of time&#44; that subsequently resolves&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">5</span></a> First described during the treatment of brain lesions&#44; this phenomenon has been observed in up to 15&#37; of patients with melanoma who receive immunotherapy&#44; but it is rare in lung cancer&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">6</span></a> with a prevalence in the latter of less than 2&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">5</span></a> apparently caused by T cells infiltrating the tumor&#44; with the resulting edema and&#47;or necrosis&#46; The absence of true progression can only be confirmed non-invasively with radiological studies&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">7</span></a> so it is sometimes very difficult to decide whether to continue or suspend treatment&#46; This has led to the WHO or RECIST criteria for the definition of therapeutic response being replaced by new immune-mediated response criteria&#44; such as the immune-related response criteria &#40;irRC&#41;&#44; the immune-related response evaluation criteria in solid tumors &#40;irRECIST1&#46;1&#41;&#44; and the immune RECIST &#40;iRECIST&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">8&#8211;10</span></a> The main contribution of these new response criteria &#40;which define pseudoprogression and unconfirmed progression&#41; is to underline that patients may be responding favorably to treatment despite a temporary increase in the tumor burden&#44; or even after the appearance of new lesions&#46; Definitive confirmation as to whether a possible pseudoprogression is true disease progression requires an increase in tumor volume confirmed in 2 imaging studies conducted at least 4&#8211;8 weeks apart&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">11</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In summary&#44; it appears that immunotherapy is changing the treatment of lung cancer&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">12&#44;13</span></a> but its use has brought with it new side effects and new challenges in the assessment of radiological response&#44; which will require new training for professionals involved in the treatment and follow-up of these patients&#46; Despite the fact that pseudoprogression seems to be rare in patients with non-small cell lung cancer treated with immunotherapy&#44; the possibility of performing invasive techniques should always be evaluated&#44; since a dense inflammatory cell infiltrate in biopsy material can help differentiate pseudoprogression from progression&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">14</span></a> Another factor to take into account is that pseudoprogression is not generally associated with a significant clinical deterioration of the patient&#44; a situation which would usually indicate real progression&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">5</span></a></p></span>"
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Scientific Letter
Pseudoprogression in a Patient with Metastatic Lung Adenocarcinoma Treated with Nivolumab
Pseudoprogresión en una paciente con adenocarcinoma pulmonar metastásico tratada con nivolumab
Alberto Cabañeroa,
Corresponding author
, Luis Gorospeb, Maria Eugenia Olmedoc, Laura Mezquitad
a Servicio de Cirugía Torácica, Hospital Universitario Ramón y Cajal, Madrid, Spain
b Servicio de Radiodiagnóstico, Hospital Universitario Ramón y Cajal, Madrid, Spain
c Servicio de Oncología Médica, Hospital Universitario Ramón y Cajal, Madrid, Spain
d Department of Adult Medicine, Institut de Cancérologie Gustave Roussy, París, France
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Axial CT images of abdomen &#40;left&#41; and pelvis &#40;right&#41; showing right inguinal lymphadenopathy&#44; a mass in the right adnexal region&#44; and another in the left paracolic gutter &#40;arrows&#41;&#46; &#40;B&#41; Axial CT images of abdomen &#40;left&#41; and pelvis &#40;right&#41; obtained 8 weeks later&#44; showing a striking increase in tumor lesions &#40;arrows&#41;&#46; &#40;C&#41; Axial CT images of abdomen &#40;left&#41; and pelvis &#40;right&#41; obtained 12 months later&#44; demonstrating the disappearance of tumor lesions&#46;</p>"
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The molecular study showed no mutations or molecular translocations &#40;EGFR&#44; KRAS&#44; BRAF&#44; ALK and ROS1-negative&#41;&#46; The patient received 2 cycles of cisplatin&#43;pemetrexed&#44; and her first follow-up CT performed 8 weeks later revealed the appearance of right inguinal lymphadenopathy and tumor-like pelvic masses located theoretically in the right uterine appendage and in the left paracolic gutter&#44; so second-line treatment with nivolumab began &#40;3<span class="elsevierStyleHsp" style=""></span>mg&#47;kg every 15 days&#41;&#46; Imaging studies performed at 8 weeks showed progression of the abdominopelvic and brain lesions&#44; and the patient&#39;s general condition had deteriorated &#40;ECOG 3&#41;&#44; so she was referred to the palliative care unit&#46; One year later&#44; she attended the clinic with improvement of her general condition &#40;ECOG 1&#41; and a CT performed for re-assessment revealed that the abdominopelvic lesions and the brain lesions seen on the head MRI had disappeared &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The patient is currently in complete radiological response after 41 months of follow-up&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">In recent years&#44; the therapeutic options for advanced non-small cell lung cancer have increased significantly&#46; This new therapeutic arsenal benefits some patients&#44; but has introduced some different forms of toxicity&#46; In this respect&#44; immunomodulatory drugs may lead to complications associated with the immune system&#44; with other comorbidities or treatments&#44; and even paradoxical responses&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">4</span></a> Pseudoprogression is a form of clinical response consisting of radiological worsening of the disease during treatment for an undetermined period of time&#44; that subsequently resolves&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">5</span></a> First described during the treatment of brain lesions&#44; this phenomenon has been observed in up to 15&#37; of patients with melanoma who receive immunotherapy&#44; but it is rare in lung cancer&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">6</span></a> with a prevalence in the latter of less than 2&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">5</span></a> apparently caused by T cells infiltrating the tumor&#44; with the resulting edema and&#47;or necrosis&#46; The absence of true progression can only be confirmed non-invasively with radiological studies&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">7</span></a> so it is sometimes very difficult to decide whether to continue or suspend treatment&#46; This has led to the WHO or RECIST criteria for the definition of therapeutic response being replaced by new immune-mediated response criteria&#44; such as the immune-related response criteria &#40;irRC&#41;&#44; the immune-related response evaluation criteria in solid tumors &#40;irRECIST1&#46;1&#41;&#44; and the immune RECIST &#40;iRECIST&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">8&#8211;10</span></a> The main contribution of these new response criteria &#40;which define pseudoprogression and unconfirmed progression&#41; is to underline that patients may be responding favorably to treatment despite a temporary increase in the tumor burden&#44; or even after the appearance of new lesions&#46; Definitive confirmation as to whether a possible pseudoprogression is true disease progression requires an increase in tumor volume confirmed in 2 imaging studies conducted at least 4&#8211;8 weeks apart&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">11</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In summary&#44; it appears that immunotherapy is changing the treatment of lung cancer&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">12&#44;13</span></a> but its use has brought with it new side effects and new challenges in the assessment of radiological response&#44; which will require new training for professionals involved in the treatment and follow-up of these patients&#46; Despite the fact that pseudoprogression seems to be rare in patients with non-small cell lung cancer treated with immunotherapy&#44; the possibility of performing invasive techniques should always be evaluated&#44; since a dense inflammatory cell infiltrate in biopsy material can help differentiate pseudoprogression from progression&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">14</span></a> Another factor to take into account is that pseudoprogression is not generally associated with a significant clinical deterioration of the patient&#44; a situation which would usually indicate real progression&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">5</span></a></p></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Axial CT images of abdomen &#40;left&#41; and pelvis &#40;right&#41; showing right inguinal lymphadenopathy&#44; a mass in the right adnexal region&#44; and another in the left paracolic gutter &#40;arrows&#41;&#46; &#40;B&#41; Axial CT images of abdomen &#40;left&#41; and pelvis &#40;right&#41; obtained 8 weeks later&#44; showing a striking increase in tumor lesions &#40;arrows&#41;&#46; &#40;C&#41; Axial CT images of abdomen &#40;left&#41; and pelvis &#40;right&#41; obtained 12 months later&#44; demonstrating the disappearance of tumor lesions&#46;</p>"
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Article information
ISSN: 15792129
Original language: English
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