Bart A. van de Wiel

Case Report of a Fatal Serious Adverse Event Upon Administration of T Cells Transduced With a MART-1-specific T-cell Receptor

Here, we describe a fatal serious adverse event observed in a patient infused with autologous T-cell receptor (TCR) transduced T cells. This TCR, originally obtained from a melanoma patient, recognizes the well-described HLA-A*0201 restricted 26-35 epitope of MART-1, and was not affinity enhanced. Patient 1 with metastatic melanoma experienced a cerebral hemorrhage, epileptic seizures, and a witnessed cardiac arrest 6 days after cell infusion. Three days later, the patient died from multiple organ failure and irreversible neurologic damage. After T-cell infusion, levels of IL-6, IFN-γ, C-reactive protein (CRP), and procalcitonin increased to extreme levels, indicative of a cytokine release syndrome or T-cell-mediated inflammatory response. Infused T cells could be recovered from blood, broncho-alveolar lavage, ascites, and after autopsy from tumor sites and heart tissue. High levels of NT-proBNP indicate semi-acute heart failure. No cross reactivity of the modified T cells toward a beating cardiomyocyte culture was observed. Together, these observations suggest that high levels of inflammatory cytokines alone or in combination with semi-acute heart failure and epileptic seizure may have contributed substantially to the occurrence of the acute and lethal event. Protocol modifications to limit the risk of T-cell activation-induced toxicity are discussed.

Inter-observer variation in the histopathology reports of head and neck melanoma; a comparison between the seventh and eighth edition of the AJCC staging system

BACKGROUND TNM staging of melanoma has recently been altered by the introduction of the 8th edition of the AJCC Cancer Staging manual. The purpose of this study is to analyze the inter-observer variation of histopathology reports and its effect on recommended treatment policy. METHODS We retrospectively analyzed 296 cases, diagnosed as primary cutaneous head and neck melanoma (2005-2016), referred to the Netherlands Cancer Institute (NCI) for treatment after prior diagnosis in another hospital (non-NCI). All reports were analyzed for patients demographics, tumor characteristics and histopathologic features. RESULTS In 53% and 40% of the cases, the histopathologic parameters were discordant, according to AJCC 7th and 8th edition, respectively. This indicated a perfect inter-observer agreement for the measurement of Breslow thickness (Intraclass correlation coefficient (ICC) = 0.981) and a substantial agreement for subtype (kappa statistic (κ) = 0.648) and ulceration (κ = 0.802), while only moderate for dermal mitotic activity (κ = 0.472). After NCI review, recommended treatment policies were changed in 13% and 11% of the patients when applying TNM 7 and TNM 8, respectively. Scheduling sentinel lymph node biopsy (SLNB) changed in 14 (5%) and 10 (3%) cases when using TNM 7 and TNM 8, respectively. CONCLUSION Review by a NCI pathologist of histopathologic parameters of primary cutaneous head and neck melanoma led to significant changes in treatment decision. Introduction of the AJCC 8th edition led to slightly less discordances between NCI and non-NCI reports and consequently smaller impact on treatment planning. Expert review remains indicated when a SLNB is considered for additional staging in selected cases.

Positron emission tomography/computed tomography evaluation of oncolytic virus therapy efficacy in melanoma

a Department of Surgical Oncology, Netherlands Cancer Institute e Antoni van Leeuwenhoek, Plesmanlaan 121, NL-1066 CX Amsterdam, The Netherlands b Department of Nuclear Medicine, Netherlands Cancer Institute e Antoni van Leeuwenhoek, Plesmanlaan 121, NL-1066 CX Amsterdam, The Netherlands c Department of Pathology, Netherlands Cancer Institute e Antoni van Leeuwenhoek, Plesmanlaan 121, NL-1066 CX Amsterdam, The Netherlands d Department of Head & Neck Surgery, Netherlands Cancer Institute e Antoni van Leeuwenhoek, Plesmanlaan 121, NL-1066 CX Amsterdam, The Netherlands