Evaluation of PET and laparoscopy in STagIng advanced gastric cancer: a multicenter prospective study (PLASTIC-study).

BACKGROUND: Initial staging of gastric cancer consists of computed tomography (CT) and gastroscopy. In locally advanced (cT3-4) gastric cancer, fluorodeoxyglucose positron emission tomography with CT (FDG-PET/CT or PET) and staging laparoscopy (SL) may have a role in staging, but evidence is scarce. The aim of this study is to evaluate the impact and cost-effectiveness of PET and SL in addition to initial staging in patients with locally advanced gastric cancer. METHODS: This prospective observational cohort study will include all patients with a surgically resectable, advanced gastric adenocarcinoma (cT3-4b, N0-3, M0), that are scheduled for treatment with curative intent after initial staging with gastroscopy and CT. The modalities to be investigated in this study is the addition of PET and SL. The primary outcome of this study is the proportion of patients in whom the PET or SL lead to a change in treatment strategy. Secondary outcome parameters are: diagnostic performance, morbidity and mortality, quality of life, and cost-effectiveness of these additional diagnostic modalities. The study recently started in August 2017 with a duration of 36 months. At least 239 patients need to be included in this study to demonstrate that the diagnostic modalities are break-even. Based on the annual number of gastrectomies in the participating centers, it is estimated that approximately 543 patients are included in this study. DISCUSSION: In this study, it is hypothesized that performing PET and SL for locally advanced gastric adenocarcinomas results in a change of treatment strategy in 27% of patients and an annual cost-reduction in the Netherlands of €916.438 in this patient group by reducing futile treatment. The results of this study may be applicable to all countries with comparable treatment algorithms and health care systems. TRIAL REGISTRATION: NCT03208621 . This trial was registered prospectively on June 30, 2017.

Preclinical imaging characteristics and quantification of Platinum-195m SPECT.

AIMS: In vivo biodistribution imaging of platinum-based compounds may allow better patient selection for treatment with chemo(radio)therapy. Radiolabeling with Platinum-195m (195mPt) allows SPECT imaging, without altering the chemical structure or biological activity of the compound. We have assessed the feasibility of 195mPt SPECT imaging in mice, with the aim to determine the image quality and accuracy of quantification for current preclinical imaging equipment. METHODS: Enriched (>96%) 194Pt was irradiated in the High Flux Reactor (HFR) in Petten, The Netherlands (NRG). A 0.05 M HCl 195mPt-solution with a specific activity of 33 MBq/mg was obtained. Image quality was assessed for the NanoSPECT/CT (Bioscan Inc., Washington DC, USA) and U-SPECT+/CT (MILabs BV, Utrecht, the Netherlands) scanners. A radioactivity-filled rod phantom (rod diameter 0.85-1.7 mm) filled with 1 MBq 195mPt was scanned with different acquisition durations (10-120 min). Four healthy mice were injected intravenously with 3-4 MBq 195mPt. Mouse images were acquired with the NanoSPECT for 120 min at 0, 2, 4, or 24 h after injection. Organs were delineated to quantify 195mPt concentrations. Immediately after scanning, the mice were sacrificed, and the platinum concentration was determined in organs using a gamma counter and graphite furnace - atomic absorption spectroscopy (GF-AAS) as reference standards. RESULTS: A 30-min acquisition of the phantom provided visually adequate image quality for both scanners. The smallest visible rods were 0.95 mm in diameter on the NanoSPECT and 0.85 mm in diameter on the U-SPECT+. The image quality in mice was visually adequate. Uptake was seen in the kidneys with excretion to the bladder, and in the liver, blood, and intestine. No uptake was seen in the brain. The Spearman correlation between SPECT and gamma counter was 0.92, between SPECT and GF-AAS it was 0.84, and between GF-AAS and gamma counter it was0.97 (all p < 0.0001). CONCLUSION: Preclinical 195mPt SPECT is feasible with acceptable tracer doses and acquisition times, and provides good image quality and accurate signal quantification.

Multimodal surgical guidance towards the sentinel node in vulvar cancer.

INTRODUCTION: Conventional sentinel node (SN) mapping is performed by injecting a radiocolloid followed by lymphoscintigraphy (and SPECT/CT imaging). An extra intraoperative injection with blue dye can then allow for optical identification of the SN. In order to improve the current clinical standard, the hybrid tracer indocyanine green (ICG)-(99m)Tc-nanocolloid was introduced, a tracer that is both radioactive and fluorescent. This feasibility study aimed to evaluate the value of a multimodal-based SN biopsy in vulvar cancer. MATERIALS AND METHODS: Fifteen patients with vulvar cancer (29 groins) scheduled for SN biopsy were peritumorally injected with ICG-(99m)Tc-nanocolloid followed by lymphoscintigraphy and SPECT/CT imaging to identify the SNs. In thirteen patients, shortly before the start of the operation, blue dye was intradermally injected around the lesion. SNs were harvested using a combination of radiotracing, fluorescence imaging, and optical blue dye detection. A portable gamma camera was used before and after SN excision to confirm excision of the preoperatively defined SNs. RESULTS: Preoperative lymphoscintigraphy and SPECT/CT imaging visualized drainage to 39 SNs in 28 groins. During the operation, 98% (ex vivo 100%) of the SNs were radioactive. With fluorescence imaging 96% of the SNs (ex vivo 100%) could be visualized. Only 65% of the SNs had stained blue at the time of excision. CONCLUSION: ICG-(99m)Tc-nanocolloid can be used for preoperative SN identification and enables multimodal (radioactive and fluorescent) surgical guidance in patients with vulvar cancer. The addition of fluorescence-based optical guidance offers more effective SN visualization compared to blue dye.

Muscarinic inhibition of salivary glands with glycopyrronium bromide does not reduce the uptake of PSMA-ligands or radioiodine.

RATIONALE: Salivary glands are highly perfused and express the prostate-specific membrane antigen (PSMA) receptor as well as the sodium-iodide symporter. As a consequence, treatment with 177Lu/225Ac-PSMA for prostate cancer or 131I for thyroid cancer leads to a high radiation dose in the salivary glands, and patients can be confronted with persistent xerostomia and reduced quality of life. Salivation can be inhibited using an antimuscarinic pharmaceutical, such as glycopyrronium bromide (GPB), which may also reduce perfusion. The primary objective of this work was to determine if inhibition with GPB could provide a considerable (> 30%) reduction in the accumulation of administered 123I or 68Ga-PSMA-11 in salivary glands. METHODS: Ten patients who already received a whole-body 68Ga-PSMA-11 PET/CT scan for (re)staging of prostate cancer underwent a repeat PET/CT scan with tracer administration at 90 min after intravenous injection of 0.2 mg GPB. Four patients in follow-up after thyroid cancer, who had been treated with one round of ablative 131I therapy with curative intent and had no signs of recurrence, received 123I planar scintigraphy at 4 h after tracer administration without GPB and a repeated scan at least one week later, with tracer administration at 30 min after intramuscular injection of 0.4 mg GPB. Tracer uptake in the salivary glands was quantified on PET and scintigraphy, respectively, and values with and without GPB were compared. RESULTS: No significant difference in PSMA uptake in the salivary glands was seen without or with GPB (Mean SULmean parotid glands control 5.57, intervention 5.72, p = 0.50. Mean SULmean submandibular glands control 6.25, intervention 5.89, p = 0.12). Three out of 4 patients showed increased 123I uptake in the salivary glands after GPB (Mean counts per pixel control 8.60, intervention 11.46). CONCLUSION: Muscarinic inhibition of salivation with GPB did not significantly reduce the uptake of PSMA-ligands or radioiodine in salivary glands, and can be dismissed as a potential strategy to reduce toxicity from radionuclide therapies.

FDG-PET/CT for response evaluation of invasive bladder cancer following neoadjuvant chemotherapy.

PURPOSE: We investigated the accuracy of FDG-PET/CT response identification following neoadjuvant or induction chemotherapy (NAIC) for invasive bladder cancer (BC) as to better select patients for radical cystectomy (RC). METHODS: Between 2010 and 2014, 37 cT1-4N1-3 BC patients received a FDG-PET/CT before and after NAIC followed by RC. Metabolic lymph node (LN) response was evaluated according to EORTC recommendations. Additionally, primary tumor response was evaluated for 23 patients by means of delayed pelvic imaging after forced diuresis. Gold standard was response on pathologic analysis of RC specimens. Response was defined as partial response (pPR, any pathologic downstaging) or complete response (pCR, 

[Utility of SPECT/CT scan for anatomical localization of pararectal and presacral sentinel nodes in prostate cancer]. / Utilidad de la SPECT-TC para la localización anatómica de los ganglios centinelas presacrales y pararrectales en el cáncer de próstata.

AIM: This study has aimed to evaluate the added value of SPECT-CT scan in the preoperative assessment of sentinel nodes of the presacral and pararectal regions localized outside the standard area of extended pelvic lymphadenectomy for the staging of the pelvis in prostate cancer. SPECT-CT scan can serve as a guide for the excision of these nodes by lymphadenectomy by open surgery or laparoscopy. MATERIAL AND METHODS: We evaluated 4 patients with prostate cancer presenting sentinel nodes in the pararectal and presacral regions on SPECT-CT scan performed in addition to lymphoscintigraphy. These patients underwent lymphadenectomy with robot-assisted laparoscopy together with prostatectomy. All of the excised lymph nodes were sent for histopathology study. RESULTS: An average of 6 sentinel nodes per patient were found on SPECT-CT scan with a mean of 2 sentinel nodes in presacral/pararectal región. Lymphadenectomy including these areas was performed. Pararectal/presacral sentinel nodes of all patients depicted by SPECT-CT scan were tumor free on histopathology study. Sentinel nodes (no pararectal/presacral) were positive for malignancy in only one patient. CONCLUSION: Preoperative SPECT-CT scan is a useful tool to localize the sentinel nodes in pararectal/presacral regions. It can be an anatomic guide for new modalities of laparoscopic surgery such as robot-assisted procedures that can access the pelvic areas visualized with SPECT-CT scan, making excision of these nodes possible.