Clinical Oncology: Case Reports

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Across Differential Diagnosis between Pseudoprogression and Hyperprogression to Immunotherapy in Non-Small Cell Lung Cancer: A Case Report of Unusual Symptomatic Pseudoprogression

Background: Immune Checkpoint Inhibitors (ICIs) administered in first-line monotherapy are the standard treatment for patients with Non-Small-Cell Lung Cancer (NSCLC) and a high expression of Programmed Cell Death-Ligand 1 (PD-L1).

Atypical response patterns to ICIs include Hyperprogressive Disease (HPD) and pseudoprogression disease. In real-world patients, the difference between those two patterns is not always easy to define.

Case Report: A 68-year-old man diagnosed with metastatic lung adenocarcinoma with a Tumor Proportional Score (TPS) of 85% started in November 2018 with the first-line treatment with monotherapy pembrolizumab q3w. After two cycles of therapy, the patient developed clinical worsening with progressive dyspnoea and fatigue. At the Computed Tomography (CT) scan a diffuse bilateral lung HPD was diagnosed. Therefore, the patient underwent a second-line therapy with carboplatin and pemetrexed, early discontinued due to severe toxicity and subsequent third-line therapy with oral metronomic vinorelbine. The patient had a clinical benefit and radiological partial response followed by long-term stability of the disease, still ongoing at the present day.

Conclusion: Our patient was diagnosed with HPD along with clinical deterioration. Some rare cases of symptomatic pseudoprogression are reported. A posteriori, our patient probably had a symptomatic pseudoprogression and the immune-modulatory activity of pembrolizumab synergically worked with the subsequent chemotherapy. Diagnosis between HPD and pseudoprogression is challenging and more precise assessment methods including also the symptomatic pseudoprogression in the differential diagnosis are needed.

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