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Light Wellness 101

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Logan Adams
Logan Adams

PDF Checkpoint 1.9.19


Importance: Many patients with advanced non-small cell lung cancer (NSCLC) receiving immunotherapy show primary resistance. High-dose radiotherapy can lead to increased tumor antigen release, improved antigen presentation, and T-cell infiltration. This radiotherapy may enhance the effects of checkpoint inhibition.




PDF Checkpoint 1.9.19



We report a case of a 53-year-old male patient with melanoma who was treated with combination immune checkpoint blockade (ICB) with ipilimumab and nivolumab. The patient had advanced disease with metastasis to the liver, lung, and lymph nodes. After two doses of ICB, the patient developed hypocalcemia as a result of an immune-mediated hypoparathyroidism that was treated with calcium and vitamin D substitution. In addition, the patient suffered from immune-related colitis that required treatment with corticosteroids and two doses of infliximab. Combination immunotherapy led to a metabolic complete remission of the melanoma. After tapering corticosteroids, the patient was continued on nivolumab for several weeks. No abnormalities of blood glucose were noted until then in an otherwise lean patient with a BMI of 19.6 kg/m2. When the patient developed a seronegative oligoarthritis affecting the right knee and both ankles, he was treated with local corticosteroid injections, but no systemic corticosteroids were used. ICB was stopped. Several days later, the patient was seen for progressive fatigue. Laboratory testing showed a mild hyponatremia and a random blood glucose of 22.3 mmol/L. HbA1c was 11.6% (103 mmol/mol), and C-peptide was 933 pmol/L. A mixed meal tolerance test (MMTT) revealed a mixed dysfunction, including impaired insulin secretion and reduced peripheral insulin sensitivity. Autoantibodies against islet cells were positive. Despite peripheral insulin resistance, positive autoantibodies and impaired insulin secretion led to the diagnosis of an immune-mediated diabetes mellitus (DM) similar to a type 1 DM with mixed features of β-cell dysfunction and peripheral insulin resistance. Because CRP levels were low throughout the observation period, systemic inflammation as the main cause of the hyperglycemia was also unlikely. Treatment with insulin injections was begun. Initially, a daily average of 17 units of insulin was required. Because the patient also developed a more active oligoarthritis, we started a therapy with infliximab to block tumor necrosis factor-α (TNF-α). Treatment with infliximab resulted in a reversal of β-cell dysfunction and insulin resistance, and insulin therapy could be stopped. Restaging of the patient 2 months after the last insulin injection and infliximab dose demonstrated an ongoing complete remission of his DM (Fig. 1). 041b061a72


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