Background Combining radioactive colloids and a near-infrared (NIR) fluorophore permit preoperative planning and intraoperative localization of deeply located sentinel lymph nodes (SLNs) with direct optical guidance by a single lymphatic tracer. The aim of this clinical trial was to evaluate and optimize a hybrid NIR fluorescence and radioactive tracer for SLN detection in breast cancer patients. Method Patients with breast cancer undergoing SLN biopsy were enrolled. The day before surgery, indocyanine green (ICG)-99mTc-Nanocolloid was injected periareolarly and a lymphoscintigram was acquired. Directly before surgery, blue dye was injected. Intraoperative SLN localization was performed by a gamma probe and the Mini-FLARETM NIR fluorescence imaging system. Patients were divided into two dose groups, with one group receiving twice the particle density of ICG and nanocolloid, but the same dose of radioactive 99mTechnetium. Results Thirty-two patients were enrolled in the trial. At least one SLN was identified pre- and intraoperatively. All 48 axillary SLNs could be detected by gamma tracing and NIR fluorescence imaging, but only 42 of them stained blue. NIR fluorescence permitted detection of lymphatic vessels draining to the SLN up to 29 hours after injection. Increasing the particle density by two-fold did not yield a difference in fluorescence intensity, median 255 (range 98 – 542) vs. median 284 (90 – 921; P = 0.590), or signal- to- background ratio, median 5.4 (range 3.0 – 15.4) vs. median 4.9 (3.5 – 16.3; P = 1.000), of the SLN. Conclusion The hybrid NIR fluorescence and radioactive tracer ICG-99mTc-Nanocolloid permitted accurate pre- and intraoperative detection of the SLNs in patients with breast cancer.

PurposeThe aim of the current study was to evaluate the relationship between the site of latest mechanical activation as assessed with gated myocardial perfusion SPECT (GMPS), left ventricular (LV) lead position and response to cardiac resynchronization therapy (CRT).MethodsThe patient population consisted of consecutive patients with advanced heart failure in whom CRT was currently indicated. Before implantation, 2-D echocardiography and GMPS were performed. The echocardiography was performed to assess LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV) and LV ejection fraction (LVEF). The site of latest mechanical activation was assessed by phase analysis of GMPS studies and related to LV lead position on fluoroscopy. Echocardiography was repeated after 6 months of CRT. CRT response was defined as a decrease of ≥15% in LVESV.ResultsEnrolled in the study were 90 patients (72% men, 67±10 years) with advanced heart failure. In 52 patients (58%), the LV lead was positioned at the site of latest mechanical activation (concordant), and in 38 patients (42%) the LV lead was positioned outside the site of latest mechanical activation (discordant). CRT response was significantly more often documented in patients with a concordant LV lead position than in patients with a discordant LV lead position (79% vs. 26%, p<0.01). After 6 months, patients with a concordant LV lead position showed significant improvement in LVEF, LVESV and LVEDV (p<0.05), whereas patients with a discordant LV lead position showed no significant improvement in these variables.ConclusionPatients with a concordant LV lead position showed significant improvement in LV volumes and LV systolic function, whereas patients with a discordant LV lead position showed no significant improvements.

Talimogene laherparepvec (T‐VEC) is a modified herpes simplex virus, type 1 (HSV‐1), which can be administered intralesionally in patients with stage IIIB/C‐IVM1a unresectable melanoma (EMA label). The phase 3 OPTiM registration study showed an overall response rate (ORR) of 26%. Since December 2016, 48 eligible patients started treatment at the Netherlands Cancer Institute. We included 26 patients in this study with a follow up time ≥6 months, reporting Overall Response Rate (ORR), Disease Control Rate (DCR), Adverse Events (AE), prior treatment for melanoma and baseline characteristics, documented in a prospectively maintained database. In house developed treatment protocol consists of clinical evaluation, periodic PET‐CT and histological biopsies for response evaluation. Median follow‐up was 12.5 months. Of 26 patients, 16 (61.5%) had a Complete Response (CR) as their best response. Seven (26.9%) patients had a Partial Response (PR) as their best response, 1 (3.8%) patient Stable Disease (SD) and 2 (7.7%) patients Progressive Disease (PD). Best ORR was 88.5%. DCR was 92.3%. Grade 1–2 AEs occurred in all patients. Mostly, these consisted of fatigue, influenza‐like symptoms and injection site erythema. All patients underwent prior treatment. Prior treatment did not influence response or toxicity of T‐VEC. Best ORR for T‐VEC monotherapy at our institute was 88.5% with 61.5% achieving a CR. This prospective study for T‐VEC in early metastatic (stage IIIB/C‐IVM1a) melanoma demonstrated superior results to the phase 3 OPTiM study and confirms the role of oncolytic immunotherapy for melanoma.

Background: Programmed cell death protein 1 (PD-1) antibody treatment is standard of care for melanoma and nonsmall-cell lung cancer (NSCLC). Accurately predicting which patients will benefit is currently not possible. Tumor uptake and biodistribution of the PD-1 antibody might play a role. Therefore, we carried out a positron emission tomography (PET) imaging study with zirconium-89 ( 89 Zr)-labeled pembrolizumab before PD-1 antibody treatment. Patients and methods: Patients with advanced or metastatic melanoma or NSCLC received 37 MBq (1 mCi) 89 Zrpembrolizumab (w2.5 mg antibody) intravenously plus 2.5 or 7.5 mg unlabeled pembrolizumab. After that, up to three PET scans were carried out on days 2, 4, and 7. Next, PD-1 antibody treatment was initiated. 89 Zrpembrolizumab tumor uptake was calculated as maximum standardized uptake value (SUV max ) and expressed as geometric mean. Normal organ uptake was calculated as SUV mean and expressed as a mean. Tumor response was assessed according to (i)RECIST v1.1. Results: Eighteen patients, 11 with melanoma and 7 with NSCLC, were included. The optimal dose was 5 mg pembrolizumab, and the optimal time point for PET scanning was day 7. The tumor SUV max did not differ between melanoma and NSCLC (4.9 and 6.5, P ¼ 0.49). Tumor 89 Zr-pembrolizumab uptake correlated with tumor response (P trend ¼ 0.014) and progression-free (P ¼ 0.0025) and overall survival (P ¼ 0.026). 89 Zr-pembrolizumab uptake at 5 mg was highest in the spleen with a mean SUV mean of 5.8 (standard deviation AE1.8). There was also 89 Zr-pembrolizumab uptake in Waldeyer's ring, in normal lymph nodes, and at sites of inflammation. Conclusion: 89 Zr-pembrolizumab uptake in tumor lesions correlated with treatment response and patient survival. 89 Zrpembrolizumab also showed uptake in lymphoid tissues and at sites of inflammation.

Neurolymphomatosis (NL) is a rare clinical entity that is defined as infiltration of the nervous system by a known or unknown haematological malignancy and is difficult to diagnose. Fluorine-18 fluorodeoxyglucose (18F-FDG) PET imaging is increasingly being used in haematological malignancies. This article focus on the role of 18F-FDG PET in the diagnosis and management of NL by presenting a review of cases described in the literature. Reports on NL that used PET with or without computed tomography (CT) as a diagnostic modality were extracted from Medline and evaluated. A total of 58 patients described in 49 case reports on NL were found. In 36 distinctive patients 18F-FDG PET with or without CT was used as a diagnostic modality. In 91% of patients PET showed uptake in various structures in the central or peripheral nervous system, suggesting involvement of lymphoma. Predilection localizations were the brachial and lumbar plexuses, along the course of peripheral nerves of the extremities, and the trigeminal nerve root. MRI, cerebrospinal fluid or bone marrow analysis were frequently negative. In the cases described in the literature 18F-FDG PET assisted in diagnosing NL by providing a whole-body evaluation, showing frequent uptake in affected nervous structures and supported disease management by defining a target for biopsy, monitoring progression and evaluating response to treatment. As other diagnostic methods may be negative, the importance of PET-CT is increasing in the diagnosis and management of this rare clinical entity.