Response to Combined Peptide Receptor Radionuclide Therapy and Checkpoint Immunotherapy with Ipilimumab Plus Nivolumab in Metastatic Merkel Cell Carcinoma.

For patients with Merkel cell carcinoma (MCC) who are refractory to immune checkpoint inhibition (ICI), treatment options are limited. Few cases of MCCs have been reported to show responses to peptide receptor radionuclide therapy (PRRT). A combination of PRRT and ICI has not been reported in MCC to date. A patient with metastatic MCC, who was resistant to first-line avelumab and acquired resistance to ipilimumab/nivolumab (IPI/NIVO) with additional radiotherapy, presented with multiple distant metastases. After confirmation of SSTR expression, treatment was continued with an additional 4 doses of IPI/NIVO combined with 2 cycles of PRRT. Treatment was well tolerated, with transient hemotoxicity and mild nausea. Restaging after 3 mo demonstrated an exceptional response. This case demonstrates the feasibility of combined treatment with IPI/NIVO and PRRT as an option for MCC patients progressing under ICI. Prospective evidence confirming the additive value of combining ICI and radionuclide therapy in a larger cohort is needed.

Comparison of hip joint cartilage degeneration assessed by histology and ex vivo optical coherence tomography.

The aim of this study is to validate optical coherence tomography (OCT) in assessing human articular cartilage by means of histological analyses. Twenty resected human femoral head specimens were evaluated with OCT and histological analysis. OCT and histological evaluation was performed according to the Bear and the Mankin criteria. OCT grades and Mankin scores (total score and sub-score structure) were correlated and intra-/inter-observer agreement for repeated OCT evaluations was tested by interclass-correlation coefficient (ICC) analysis. OCT grades and Mankin scores were correlated [Spearman correlation=0.742 (total) and 0.656 (structure), P<0.001], revealing significant differences between the histological scores in various OCT grades of cartilage degeneration (P<0.001). Intra-observer (ICC 0.930) and inter-observer (ICC 0.933) reliability was high (P<0.001). OCT appears to be reliable in the assessment of human articular cartilage. Further studies on intra-operative cartilage evaluation by OCT are necessary to substantiate its applicability in clinical routine.

Validity of gradient-echo three-dimensional delayed gadolinium-enhanced magnetic resonance imaging of hip joint cartilage: a histologically controlled study.

OBJECTIVE: To validate gradient-echo three-dimensional (3D) delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) by means of histological analyses in the assessment of hip joint cartilage. MATERIALS AND METHODS: Twenty-one femoral head specimens collected from 21 patients (7 males, 14 females, mean age: 60.9 ± 9.6 years; range: 37.6-77.3 years), who underwent total hip replacement for symptomatic hip joint osteoarthritis, underwent MRI and histological assessment. A region of 2 cm(2) at the weight-bearing area was marked with four pins to enable multi-planar MRI reformatting to be matched with histological sections. MRI was performed at 3T with a 3D double-echo steady-state (DESS) sequence for morphological cartilage assessment and 3D Volumetric Interpolated Breathhold Examination (VIBE) for T1(Gd) mapping. Histological sections were evaluated according to the Mankin score system. Total Mankin score, grade of toluidine staining (sensitive for glycosaminoglycan content) and a modified Mankin score classification system with four sub-groups of cartilage damage were correlated with MRI data. RESULTS: Spearman's rho correlation analyses revealed a statistically significant correlation between T1(Gd) mapping and histological analyses in all categories including total Mankin score (r=-0.658, p-value ≤ 0.001), toluidine staining (r=-0.802, p-value<0.001) and modified Mankin score (r=-0.716, p-value<0.001). The correlation between morphological MRI and histological cartilage assessment was statistically significant but inferior to the biochemical cartilage MRI (r-values ranging from -0.411 to 0.525, p-values<0.001). CONCLUSIONS: Gradient-echo dGEMRIC is reliable while offering the unique features of high image resolution and 3D biochemically sensitive MRI for the assessment of early cartilage degeneration.