The use of immune checkpoint inhibitors (ICIs) is rising exponentially in numerous cancers, but immune-related adverse events can occur. We report a rare case of high-grade drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome developed stepwise in a patient with gastric cancer after nivolumab treatment. Subclinical myocarditis was sensitively detected by cardiovascular magnetic resonance 3 weeks after initiating nivolumab. Eruption, eosinophilia, and interstitial pneumonitis occurred 1 week later. Corticosteroids were started and his condition improved. Four months later, when he was still on steroids tapering off, acute kidney injury and sequential herpes zoster virus activation developed. Severe acute tubulointerstitial nephritis (ATN) with an intense infiltration of lymphocytes was observed on renal biopsy. In blood, a substantial shift to Th2 response, an increase of Th17 cells, and strikingly enriched granzyme B+ and perforin+ CD8+ T cells were detected at ATN onset. Serum interleukin (IL)-5, IL-17, interferon gamma, and IL-6 levels were consistently elevated. Further molecular profiling identified a DRESS risk allele human leukocyte antigen (HLA)-A*31:01 in this patient. His ATN responded favorably to a high dose of corticosteroids. In parallel, complete antitumor response was observed during the clinical course of DRESS. This is the first ever case report of nivolumab-associated DRESS syndrome with exploration of the mechanisms from the histopathological, cellular and molecular aspects. Nivolumab-induced DRESS may result from type IV hypersensitivity-related ‘off-target effect’ and PD-1 block-mediated ‘on-target effect’. HLA risk alleles may constitute the genetic susceptible basis. HLA typing assay has the potential to screen susceptible individuals to avoid ICI-induced DRESS.

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Objective In this cohort study, we determined the clinical value of the maximum standardized uptake value (SUVmax) of primary tumors in non‐small cell lung cancer (NSCLC). Study Design A retrospective review of NSCLC patients was performed from January 2011 to December 2017. Peripheral cN0 NSCLC patients with tumor size ≤2 cm were included. SUVmax was calculated as a continuous variable for semiquantitative analyses. A receiver operating characteristic curve was analyzed to assess the cutoff threshold of SUVmax on pathological (p) nodal metastasis. We further evaluated the clinical relevance of SUVmax in peripheral cN0 NSCLC patients. Results A total of 670 peripheral NSCLC patients with tumor size ≤2 cm were deemed cN0 by preoperative PET/CT scan. Statistical analyses suggested significant correlations of SUVmax with smoking status (P = .026), tumor volume (P = .001), pathology type (P = .008), tumor differentiation (P < .001), vessel invasion (P = .001), plural invasion (P < .001), pT stage (P < .001), nodal involvement (P < .001), and pathological tumor node metastasis stage (P < .001). A cutoff point of SUVmax of 3.8 (P < .001) could be used to predict pathological nodal metastasis. Multivariable analyses indicated that preoperative SUVmax >3.8 (odds ratio, 12.149; P < .001) was an independent predictor of nodal metastasis. Overall survival analyses further suggested that SUVmax was an independent prognostic indicator (hazard ratio, 2.050; P = .017). Conclusion Preoperative SUVmax is a predictor of pathological nodal metastasis and prognosis for peripheral cN0 NSCLC patients with tumor size ≤2 cm. Our results indicate that assessment of PET SUVmax could improve stratification of these patients.