Detection Of Metastatic Lesions Research Articles

Low-keV virtual monoenergetic imaging reconstructions of excretory phase spectral dual-energy CT in patients with urothelial carcinoma: A feasibility study

ObjectivesTo compare objective and subjective image quality between low keV virtual monoenergetic images (VMI) of the excretory phase and conventional venous phase images derived from spectral dual-energy CT (DECT) in the assessment of urothelial carcinoma. Methods26 consecutive patients with histologically confirmed urothelial carcinoma who received clinically indicated venous- and excretory phase abdominal CT scans were included retrospectively. Attenuation, image noise as well as signal- and contrast-to-noise-ratio (SNR, CNR) in venous and excretory phase CT and excretory phase VMI from 40 to 70 keV were obtained from ROI-based measurements in the following regions: urothelial carcinoma, liver, pancreas, renal cortex, subcutaneous fat, renal vein/artery, portal vein, urinary bladder wall, lymph nodes, prostate/uterus. Subjective vessel contrast and delineation of primary tumor manifestations and distant metastases were rated on 5-point Likert scales. ResultsIn comparison to venous phase CT, attenuation and SNR in excretory phase VMI40keV were higher (p < 0.001), except for liver parenchyma, where they were comparable (p = 0.07 and p = 0.17, respectively). Regarding image noise, no significant difference was found between venous phase CT and excretory phase VMI40keV (p-range: 0.08–1.00), except for liver, portal vein and renal artery, where it was lower in VMI40keV (p < 0.05). CNR of urothelial carcinoma to circumjacent bladder wall was significantly higher in excretory phase VMI40keV compared to venous phase CT. Subjective vessel contrast and delineation of primary tumor and distant metastases received equivalent or higher Likert scores in excretory phase VMI40keV than in venous phase CT. ConclusionThis feasibility study indicates that in the assessment of urothelial carcinoma, virtual monoenergetic excretory phase images at 40 keV acquired with spectral DECT could be feasible to maintain subjective and objective image quality as provided by conventional venous phase images. Still, equivalence with regards to metastatic lesion detection requires further investigation before employing this technique in a potential signal-scan, single-bolus approach.

Highlights of This Issue

Cancers with an immunosuppressive tumor microenvironment (TME) are less likely to respond to immunotherapy. In this study, Bhatia and colleagues treated ten Merkel cell carcinoma patients with intratumoral G100, a TLR4 agonist. G100 treatment led to an immunologically active TME with increased infiltration and activation of CD8+ and CD4+ T cells. Two out of three patients with locoregional disease showed sustained responses greater than 41 months. Of seven patients with metastatic disease, two showed partial responses lasting at least 33 months. Treatment was well-tolerated with mild local inflammation and no systemic toxicity. Intratumoral G100 warrants additional investigation, both as a monotherapy and in combination with other agents.Identifying patients who are most likely to respond to adjuvant therapy remains a major challenge in the treatment of many cancers, including renal cell carcinoma (RCC). George and colleagues investigated correlations between improved disease-free survival (DFS) and single nucleotide polymorphisms (SNPs) in angiogenesis- and hypoxia-related genes. SNPs in VEGFR1, VEGFR2, and eNOS were associated with improved DFS in patients with high-risk RCC who received adjuvant sunitinib, a VEGF inhibitor. This study identified SNPs that should be further tested for their potential to help identify the patients most likely to benefit from adjuvant sunitinib treatment, while reducing unnecessary toxicity risk in others.The effective detection of metastatic lesions is often not feasible until a cancer has become advanced. Hausner and colleagues describe a novel approach to detect metastases using PET imaging. An integrin αvβ6 binding peptide was radiolabeled with 4-[18F]fluorobenzoic acid ([18F]αvβ6-BP); this peptide was found to bind specifically to integrin αvβ6, which is uniquely expressed on cancer cells, in in vitro and in vivo models. The authors extended their study to several patients, concluding that [18F]αvβ6 -BP was effective in revealing primary tumors and metastases smaller than 1 cm in several organs (including brain, bone, liver, and lung) using PET imaging. This molecule has the potential to vastly improve the early detection of metastatic disease.Despite harboring actionable mutations, many cancers ultimately develop resistance to targeted therapy. Suzawa and colleagues examined clinical and genomic data from 113 lung cancer patients harboring METex14 alterations to identify mechanisms through which resistance to MET tyrosine kinase inhibitors occur. Patients were more likely to harbor concurrent activating KRAS mutations in METex14 cancers than in cancers dependent on other driver alterations. KRAS mutation or amplification was found to cause resistance to MET inhibition through constitutive activation of the RAS/ERK pathway. Combining MET inhibition with EGFR/ERBB2 inhibition successfully reduced the growth of dual-mutant cells both in vitro and in vivo, providing a potential therapeutic combination to combat resistance to MET inhibitors in lung cancer patients.

Isolated chemoperfusion of the lung and pleura as a method of treatment in children with common forms of solid bone tumors

Introduction. Therapy of malignant tumors is one of the most important problems of modern pediatric oncology. The presence of distant metastases is considered as the main sign of generalization of the tumor process. In order to improve the results of treatment of these patients, we proposed to supplement cytoreductive surgery with intraoperative isolated chemoperfusion of the lung and/or pleura with cytostatic. The purpose of the study is to determine the effectiveness of metastasectomy combined with isolated lung/pleura chemoperfusion (ILCP/PCP) under conditions of hyperoxia in children. Materials and methods. For 10 years of research (2008–2018) on the basis of the N.N. Petrov National Medical Research Center of Oncology produced 45 ILCP and PCP in 30 patients with intrapulmonary and intrapleural metastases of various malignant bone tumors. The ILCP method is a surgical procedure, during which the lung is temporarily switched off from the circulation and perfused with modified saline containing high concentrations of an antitumor drug (melphalan or cisplatin), which allows delivery of high doses of cytostatics while avoiding systemic exposure to the drug. In cases of detection of metastatic lesions of the parietal pleura after metastasectomy, PCP was performed, consisting in drainage of the pleural cavity and intraoperatively conducting, after suturing the surgical wound, hyperthermic (42 o С) chemoperfusion of the pleural cavity with a cisplatin solution for 2 hours. Results. In children with malignant bone tumors, 37 isolated chemoperfusions with cisplatin and 8 with melphalan were performed. In 27 patients, 36 ILCP were performed, in 7 patients – 9 PCP. Nine (20 %) patients underwent bilateral perfusion with an interval from 1.5 to 31 months. There were no lethal outcomes during operations and in the postoperative period. The average duration of surgical interventions was 270 ± 90 (120–520) minutes. The number of remote foci – from 1 to 56 (average value – 9). The average blood loss was 300 ± 200 (150–1000) ml. The mean follow-up was 45 months; median overall survival – 38 months; 3-year overall survival – 65.5 ± 9.4 %. Survival without progression – 40.5 ± 10.5 % (n = 30). Conclusions. ILCP/PCP with cytostatics is a method of complex therapy that can improve the quality and increase the life expectancy of patients, especially with the exhausted possibility of other treatment options.

Performance characteristics of EUS-FNA biopsy for adrenal lesions: A meta-analysis.

Background and Objective:The role of EUS-FNA biopsy (EUS-FNAB) for detection of metastatic lesions (mets) to adrenals has not been evaluated systematically. Our aim is to systematically evaluate the performance characteristics of EUS-FNAB in detecting metastasis to the adrenal glands.Materials and Methods:We performed a systematic search on PubMed and OvidSP from January 1990 to July 2016 using various search terms for EUS and adrenal lesion. Only articles published in English literature were included in the study. Studies with fewer than 10 patients were excluded from the study. Publication bias was assessed using Begg-Mazumdar test and visual inspection of funnel plots.Results:Eight studies including 360 adrenal lesions that underwent EUS-FNAB were identified. Of these, 137 FNABs were conclusive for malignancy. Sensitivity of EUS-FNAB in detecting metastasis to the adrenals was 95% (95% confidence interval [CI]: 90%–98%) and specificity was 99% (95% CI: 96%–100%). Pooled positivity of EUS-FNAB in detecting lung cancer metastasis to the adrenals was 44% (95% CI: 31.5%–57.3%). No evidence of publication bias was noted.Conclusion:Our study demonstrates that EUS-FNAB is highly sensitive and specific in detecting metastasis to adrenals. It also shows that up to about half of the patients with lung cancer and adrenal lesions on imaging have metastasis, a finding with profound implications on lung cancer staging and treatment.

The implications of intradural extension in paraspinal malignant peripheral nerve sheath tumors: effects on central nervous system metastases and overall survival.

OBJECTIVEIn this study, the authors sought to compare tumors with intradural extension to those remaining in the epidural or paraspinal space with the hypothesis that intradural extension may be a mechanism for seeding of the CSF with malignant cells, thereby resulting in higher rates of CNS metastases and shorter overall survival.METHODSThe authors searched the medical record for cases of malignant peripheral nerve sheath tumors (MPNSTs) identified from 1994 to 2017. The charts of the identified patients were then reviewed for tumor location to identify patients with paraspinal malignancy. All patients included in the study had tumor specimens that were reviewed in the surgical pathology department. Paraspinal tumors with intradural extension were identified in the lumbar, sacral, and spinal accessory nerves, and attempts were made to match this cohort to another cohort of patients who had paraspinal tumors of the cranial nerves and lumbar and sacral spinal regions without intradural extension. Further information was collected on all patients with and without intradural extension, including date of diagnosis by pathology specimen review; nerve or nerves of tumor origin; presence, location, and diagnostic date of any CNS metastases; and either the date of death or date of last follow-up.RESULTSThe authors identified 6 of 179 (3.4%) patients who had intradural tumor extension and compared these patients with 12 patients who harbored paraspinal tumors that did not have intradural extension. All tumors were diagnosed as high-grade MPNSTs according to the surgical pathology findings. Four of 6 (66.7%) patients with intradural extension had documented CNS metastases. The presence of CNS metastases was significantly higher in the intradural group than in the paraspinal group (intradural, 66.7% vs paraspinal, 0%; p < 0.01). Time from diagnosis until death was 11.2 months in the intradural group and approximately 72 months in the paraspinal, extradural cohort.CONCLUSIONSIn patients with intradural extension of paraspinal MPNSTs, significantly higher rates of CNS metastases are seen with a reduced interval of time from diagnosis to metastatic lesion detection. Intradural tumor extension is also a poor prognostic factor for survival, with these patients showing a reduced mean time from diagnosis to death.

Narrow-Band Imaging Improves Detection of Colorectal Peritoneal Metastases: A Clinical Study Comparing Advanced Imaging Techniques

BackgroundColorectal peritoneal metastases (PM) are often diagnosed in an advanced disease stage. Cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) improve survival of patients with colorectal PM, although most benefit is seen in patients with limited peritoneal disease. Advanced imaging techniques might improve the detection of PM, potentially leading to earlier diagnosis and improved cytoreduction. This prospective clinical trial compared three advanced techniques with conventional white-light imaging for the detection of colorectal PM: narrow-band imaging (NBI), near-infrared indocyanine green fluorescent imaging (NIR-ICG), and spray-dye chromoendoscopy (SDCE).MethodsPatients with colorectal PM were prospectively included. Prior to cytoreduction and HIPEC, all abdominal regions were inspected with white-light imaging, NBI, NIR-ICG, and SDCE during exploratory laparoscopy. Primary endpoints were sensitivity and specificity for the detection of PM, using pathological examination of biopsied lesions as the reference standard. The safety of all techniques was assessed.ResultsBetween May 2016 and March 2018, four different techniques were analyzed in 28 patients, resulting in 169 biopsies. Sensitivity for the detection of PM significantly increased from 80.0% with white light to 96.0% with NBI (p = 0.008), without loss of specificity (74.8% vs. 73.1%, respectively, p = 0.804). The use of NIR-ICG and SDCE was discontinued after 10 patients had undergone treatment because the lesions were not fluorescent using NIR-ICG, and because SDCE did not visualize the whole peritoneum. No adverse events relating to the imaging techniques occurred.ConclusionNBI substantially increased the detection of PM. This method is safe and could improve the detection of metastatic lesions and help optimize cytoreduction in patients with colorectal PM.

Impact of three-dimensional visualization technology on surgical strategies in complex hepatic cancer.

Surgical resection is still the mainstay of treatment for primary liver cancer (PLC). It is unclear whether three-dimensional visualization (3DV) preoperative evaluation and simulated liver resection would affect the surgical strategies and improve the R0 resection rates of patients with complex PLC when compared with the 2D evaluation using computed tomography or magnetic resonance imaging. In the study, patients with complex PLC who were subjected to laparotomy underwent both 2D and 3DV evaluation before operation. A comparison between the 2D and 3DV evaluation was compared with the gold standard of laparotomy findings. In this study, of 335 patients with complex PLC, 71 were assessed to have resectable tumors. 2D and 3DV assessments determined 63 and 71 patients to have resectable PLC, respectively. At laparotomy 69 of the 71 patients were found to have resectable PLC, but 2 patients were found to be unresectable because of detection of metastatic lesions on laparotomy, which were not detected either by 2D or 3DV preoperative evaluation. The accuracy, false positive and false negative rates of the 2D and the 3DV preoperative assessments in determining tumor resectability were 85.9%, 2.8%, 11.3%, and 97.2% (p < 0.05), 2.8%, 0%, respectively. The 3DV and 2D preoperative evaluation revealed 17 and 13 patients with vascular anomalies, respectively. There were 4 patients with major vascular anomalies not detected by 2D evaluation, whose surgical strategies were modified by 3DV evaluation. These results suggested 3DV preoperative assessment could lead to better in evaluating tumor resectability, with potential benefit in the modification of surgical strategy for patients with complex PLC.

Poly r(C) Binding Protein 1 Regulates Posttranscriptional Expression of the Ubiquitin Ligase TRIM56 in Ovarian Cancer.

Our earlier work has shown that the E3 ligase TRIM56 messenger RNA (mRNA) level and vimentin protein expression followed an inverse correlation in ovarian carcinoma patients; however, the regulatory mechanisms underlying TRIM56 expression is unclear. Steady state expression of TRIM56 mRNA expression in the normal ovarian cell line Moody and ovarian cancer cell lines SKOV-3, A2780, and Caov-3 were not significantly different; however, TRIM56 protein expression was significantly lower in the ovarian cancer cell lines compared to the Moody cell line. Polysome profiling showed significant increase in translation of TRIM56 messenger RNA in the Moody cells compared to the SKOV-3 cells. We performed RNA-affinity pulldown using biotinylated TRIM56 5 'and 3'-UTR and postnuclear extracts from Moody and SKOV-3 cells. Whereas no notable difference was observed in affinity pull-down obtained with the 5'-UTR, there was obvious difference in protein binding patterns with the 3'-UTR. Mass spectrometry was used to determine the most differentially binding protein as poly r (c) binding protein 1 (PCBP1). PCBP1 expression and binding to the 3'-UTR was both higher in SKOV-3 cells compared to the Moody cells. Silencing of TRIM56 in Moody cells cause an increase in in vitro migration and invasion, and a similar effect was mimicked by overexpression of PCBP1. Conversely, silencing of PCBP1 or overexpression of TRIM56 in SKOV-3 cells significantly decreased in vitro migration and invasion. In xenograft assays, SKOV-3 cells stably overexpressing shRNA targeting PCBP1 decreased metastasis, whereas shRNA-targeting TRIM56 potentiated detection of metastatic lesions, compared to the parental SKOV-3 cells themselves. Taken together our results reveal a yet undefined posttranscriptional regulatory mechanism underlying low expression of TRIM56 in ovarian cancer. © 2018 IUBMB Life, 71(1):177-182, 2019.

DIAGNOSTIC METHODS OF CANINE TRANSMISSIBLE VENEREAL SARCOMA

Modern diagnostic of oncological diseases, along with classical clinical and morphological methods, provides for the mandatory use of instrumental immunological, immunocytochemical and molecular genetic research methods. The main tasks of such a complex of diagnostic measures are aimed at monitoring oncological diseases at all stages of the diagnostic and treatment process, namely: the detection of a tumor at early stages of its development and the study of changes in metabolic processes in the body under the influence of neoplasms, morphological confirmation of the diagnosis, identification of histostructure and histogenesis of the tumor, determination the degree of its malignancy, detection of metastatic lesion (regional and distant lymph nodes and other organs) or assessment of the risk of its occurrence. It is well know that the early stages of oncological diseases are difficult to diagnose. At the same time, early detection of the disease can save or significantly extend the life of the patient. In such cases, the determination in the blood of specific substances, which are produced by tumors of the respective organs, the so-called oncomarkers, has been successfully used by world medical practice for more than 40 years to establish the affected organ. In combination with instrumental methods (ultrasound, endoscopy, X-ray), diagnostic efficiency is sharply increasing. Successful treatment of malignant tumors is possible under the conditions of their early detection and thorough histological diagnosis. Almost 50 % of the total number of oncologically diseased dogs has tumorous processes in the tissues of their genital organs, aggressiveness and metastasis, which often leads to lethal consequences, even after radical interventions. The aim of our research was to study the histological, cytological and immunohistochemical characteristics of transmissible venereal sarcoma. It has be en established that histologically, the tumor belongs to the low-differentiated round-cellular sarcoma of the alveolar type. Typical is tumor infiltration by lymphocytes, plasma cells, macrophages. Tumor cells are characterized by the presence of a mesenchymal marker vimentine. A positive local reaction on myogenin, cytokeratin and negative on CD31, CD34, S-100 protein and desmin was observed.

CAPABILITIES OF MAGNETIC RESONANCE IMAGING IN THE DETECTION OF METASTATIC LESION OF THE SPINE AND PELVIC BONES IN PATIENTS WITH PERIPHERAL NON-SMALL CELL LUNG CANCER

Objective. To comparatively analyze the diagnostic capabilities of magnetic resonance imaging (MRI) of the spine and pelvic bones with the results of 18F-FDG positron emission computed tomography (PET/CT) and single-photon emission computed tomography (SPECT/CT) in the detection of skeletal metastases in patients with peripheral non-small cell lung cancer (PNSCLC) in order to elaborate optimal approaches to using radiation and nuclear diagnostic techniques. Material and methods. Seventy-one patients with PNSCLC underwent a comprehensive examination of the skeleton regardless of whether they had clinical symptoms of bone lesions. MRI of the spine and pelvic bones, 18F-FDG PET/CT, and SPECT/CT were performed in all the patients with PNSCLC. The investigators analyzed MRI changes in different skeletal parts (cervical, thoracic, lumbar spine, sacrum and pelvic bones) in patients with PNSCLC and compared the findings with the results of a set of radiation and nuclear diagnostic techniques (18F-FDG PET/CT, SPECT/CT). The sensitivity, specificity and diagnostic accuracy of imaging techniques were compared. Clinical cases are presented. Results. 18F-FDG PET/CT is superior to MRI for the detection of metastatic lesions of the spine and pelvic bones. The sensitivity, specificity, and diagnostic accuracy of MRI for the identification of metastases in the spine and pelvic bones were 95.65, 96.8, and 95.85%, respectively. Those of 18F-FDG PET/CT in the detection of bone metastases were 98.7, 99.9, and 99.6%, respectively. Conclusion. 18F-FDG PET/CT is indicated for all patients with PNSCLC to rule out skeletal metastases. It is expedient to perform MRI if there are technical problems with 18F-FDG PET/CT for the detection of metastatic lesion of the spine and pelvic bones.

Multiparametric Whole-body MRI with Diffusion-weighted Imaging and ADC Mapping for the Identification of Visceral and Osseous Metastases From Solid Tumors

The purpose of this study was to investigate the use of multiparametric, whole-body, diffusion-weighted imaging (WB-DWI) and apparent diffusion coefficient (ADC) maps with T2-weighted magnetic resonance imaging (MRI) at 3T for the detection and monitoring of metastatic disease in patients. Fifty-four participants (32 healthy subjects and 22 patients) were scanned with WB-DWI methods using a 3T MRI scanner. Axial, sagittal, or coronal fat-suppressed T2-weighted (T2WI), T1-weighted (T1WI), and DWI images were acquired. Total MRI acquisition and set-up time was approximately 45 minutes. Metastatic disease on MRI was confirmed based on T2WI characteristics. The number of lesions was established on computed tomography (CT) or positron emission tomography (PET-CT). Whole-body ADC maps and T2WI were constructed, and region-of-interests were drawn in normal and abnormal-appearing tissue for quantitative analysis. Statistical analysis was performed using a paired t tests and P < .05 was considered statistically significant. There were 91 metastatic lesions detected from the CT or PET-CT with a missed recurrent lesion in the prostate. Multiparametric WB-MRI had excellent sensitivity (96%) for detection of metastatic lesions compared to CT. ADC map values and the ADC ratio in metastatic bone lesions were significantly increased (P < .05) compared to normal bone. In soft tissue, ADC map values and ratios in metastatic lesions were decreased compared to normal soft tissue. We have demonstrated that multiparametric WB-MRI is feasible for oncologic staging to identify bony and visceral metastasis in breast, prostate, pancreatic, and colorectal cancers. WB-MRI can be tailored to fit the patient, such that an "individualized patient sequence" can be developed for a comprehensive evaluation for staging and response during treatment.

Oncological and postoperative outcome of salvage PSMA-radioguided surgery in recurrent prostate cancer.

270 Background: Positron-emission tomography (PET) directed against PSMA allows detection of even small metastatic prostate cancer (PC) lesions at low PSA values. In a subset of patients (pts) with recurrent PC salvage surgery might be beneficial. To facilitate removal during salvage surgery, we recently introduced PSMA-targeted radioguided surgery (PSMA-RGS). Methods: 121 consecutive patients with recurrent PC (PSA median: 1.13 ng/ml, range: 0.00 – 13.90 ng/ml; 9 pts under androgen-deprivation therapy) and soft-tissue lesions on 68Ga-PSMA PET after radical prostatectomy underwent 111In- or 99mTc-based PSMA-RGS between April 2014 and May 2017. The rate of complete biochemical response (cBR; PSA &lt; 0.2ng/ml) was determined 6-16 weeks following PSMA-RGS. Biochemical recurrence-free survival (bRFS), PC-specific treatment-free survival and postoperative complications were evaluated. Results: Metastatic soft-tissue lesions from PC metastases could be removed in 120/121 pts (99.2%). One patient died six days postoperatively from a pulmonary embolism, five patients were lost to follow-up. Eleven pts suffered from Clavien grade III complications within 90d from surgery. In 75 out of 115 (65.2%) pts cBR was achieved. cBR was more likely in patients with a preoperative PSA level &lt; 1.13 (76.3% vs. 52.7%) or a single anatomical location of recurrence (71.9% vs. 58.8%). Median bRFS was 5.1 months. At the time of analysis, 15 pts exhibited an ongoing cBR for at least 12 months (range: 12-32 months). A significantly longer bRFS was achieved in pts with a preoperative PSA &lt; 1.13 ng/ml (median 14.9 vs 3.2 months, p = 0.02). In pts with a single compared to multiple location of recurrence we observed a trend towards a longer median bRFS (8.2 months vs. 3.5 months, p = 0.08). After one year of follow-up, 61.6 % of pts did not receive any further PC-directed treatment. Conclusions: PSMA-RGS is a promising tool to enhance intraoperative detection of metastatic lesions in PC with an acceptable complication rate. It leads to a high number of biochemical response with substantial duration in a subset of pts. Our data showed that bRFS was highest in patients with a low preoperative PSA and a single anatomical site of recurrence.

Novel technology of molecular radio-guidance for lymph node dissection in recurrent prostate cancer by PSMA-ligands.

Recently, prostate-specific membrane antigen-radioguided surgery (PSMA-RGS) has been introduced as a promising new and individual treatment concept in patients with localised recurrent prostate cancer (PC). In the following, we want to review our experience with PSMA-RGS in patients with localised biochemical recurrent PC. A non-systematic review of the literature was carried out with focus on technical and logistical aspects of PSMA-RGS. Furthermore, published data on intraoperative detection of metastatic lesions compared to preoperative PSMA-PET and postoperative histopathology, postoperative complications as well as oncological follow-up data are summarized. Finally, relevant aspects on prerequisites for PSMA-RGS, patient selection, and the potential benefit of additional salvage radiotherapy or potential future applications of robotic PSMA-RGS with drop-in γ-probes are discussed. First results show that PSMA-RGS is very sensitive and specific in tracking suspicious lesions intraoperatively. Prerequisite for patient selection and localisation of tumour recurrence is a positive Ga-HBED-CC PSMA positron-emission tomography (PET) scan with preferably only singular soft tissue or lymph node recurrence after primary treatment. Furthermore, PSMA-RGS has the potential to positively influence oncological outcome. PSMA-RGS seems to be of high value in patients with localised PC recurrence for exact localisation and resection of oftentimes small metastatic lesions using intraoperative and ex vivo γ-probe measurements. However, patient identification on the basis of Ga-HBED-CC-PSMA PET imaging as well as clinical parameters is crucial to obtain satisfactory results.

Abdominal CT protocol’s influence on postoperative follow-up of lesions detection associated with gastrointestinal tumours

Background: Postoperative abdominal computed tomography (CT) follow-up for gastrointestinal tumours is used to monitor therapeutic effects and detect relevant lesions, while the effective dose (ED) associated with dual-phase enhanced CT (DPCT) can be more than 20 mSv. In this study, we investigated the diagnostic utility of abdominal CT protocols based upon radiation dose control. Methods: In this institutional ethics review board-approved retrospective study, the electronic pathology database in authors’ hospital was searched for all cases of gastrointestinal tumours from June 2016 to June 2017, yielding 200 cases with complete information of clinical history and CT examination. CT scans were separated into six groups, including non-enhanced CT (NECT), arterial phase contrast-enhanced CT (APCT), venous phase contrast-enhanced CT (VPCT), NECT + APCT, NECT + VPCT and NECT + DPCT. ED was calculated for each group, and the detectability of relevant lesions was compared. Results: The ED of NECT, APCT, VPCT, NECT + APCT, NECT + VPCT and NECT + DPCT were 7.27±1.64, 7.32±1.65, 9.17±2.07, 14.55±3.29, 16.41±3.71 and 23.70±5.36 mSv, respectively. The six groups according to CT protocols showed no signi cant differences in the detection of anastomosis. For the detectability of metastatic lesions, VPCT is equivalent to NECT + DPCT. In addition, VPCT is comparable to NECT + APCT in nding lymphadenopathy. Conclusions: Postoperative VPCT follow-up for gastrointestinal tumours is comparable to conventional NECT + DPCT in the detection of relevant lesions postoperatively. The radiation dose of single VPCT is 62% less than NECT + DPCT.

The use of PET/CT in prostate cancer.

Positron emission tomography/computed tomography (PET/CT) has recently emerged as a promising diagnostic imaging platform for prostate cancer. Several radiolabelled tracers have demonstrated efficacy for cancer detection in various clinical settings. In this review, we aim to illustrate the diverse use of PET/CT with different tracers for the detection of prostate cancer. We searched MEDLINE using the terms 'prostate cancer', 'PET', 'PET/CT' and 'PET/MR'). The current review was limited to 18F-NaF PET/CT, choline-based PET/CT, fluciclovine PET/CT and PSMA-targeted PET/CT, as these modalities have been the most widely adopted. NaF PET/CT has shown efficacy in detecting bone metastases with high sensitivity, but relatively low specificity. Currently, choline PET/CT has been the most extensively studied modality. Although having superior specificity, choline PET/CT suffers from low sensitivity, especially at low PSA levels. Nevertheless, choline PET/CT was found to significantly improve upon conventional imaging modalities (CIM) in the detection of metastatic lesions at biochemical recurrence (BCR). Newer methods using fluciclovine and PSMA-targeted radiotracers have preliminarily demonstrated great promise in primary and recurrent staging of prostate cancer. However, their superior efficacy awaits confirmation in larger series. PET/CT has emerged as a promising staging modality for both primary and recurrent prostate cancer. Newer tracers have increased detection accuracies for small, incipient metastatic foci. The clinical implications of these occult PET/CT detected disease foci require organized evaluation. Efforts should be aimed at defining their natural history as well as responsiveness and impact of metastasis-directed therapy.

Clinical value of 68Ga-PSMA-11 PET/CT in the diagnosis of castration-resistant prostate cancer

Objective To assess the role of 68Ga-N, N′-bis(2-hydroxy-5-(carboxyethyl)benzyl) ethylenediamine-N, N′-diacetic acid(HBED-CC)-(Ahx)Lys-CO-Glu(PSMA-11) PET/CT on the detection of metastatic lesions from castration-resistant prostate cancer (CRPC). Methods Sixteen patients with CRPC who underwent 68Ga-PSMA-11 PET/CT between January 2015 and November 2015 were recruited in this study. Mean age of patients was (72±9) years. The PSA levels were 4-12 356 μg/L, Gleason score was 7-10. PET/CT was performed at 1 h postinjection of 68Ga-PSMA-11. Patient-based analysis and lesion-based analysis were performed. ROI analysis was used to calculate the tumor uptake (SUVmax). Final diagnosis was based on histopathology and results of other imaging examinations(99Tcm-MDP imaging, MRI). χ2 test was used to compare the diagnostic efficiencies of PET and CT. Results No adverse effects were observed in patients. 68Ga-PSMA-11 PET/CT showed moderate physiologic uptake in salivary glands and proximal small intestine, with predominant tracer clearance by the kidneys. All patients were positive on 68Ga-PSMA-11 PET/CT. Bone metastasis was found in 16 patients, liver metastasis in 2 patients (5 lesions), and lymph node metastasis in 4 patients (26 lesions). The SUVmax of liver, lymph node and bone metastases were 15.06±2.77, 7.54±5.20, 19.01±16.96, respectively. The diagnostic sensitivity, specificity and accuracy on bone metastasis with 68Ga-PSMA-11 PET and CT were 96.30%(52/54) vs 61.11%(33/54), 3/3 vs 1/3, 96.49%(55/57) vs 59.65%(34/57). The sensitivities and accuracies of the two modalities were significantly different(χ2=19.943, 22.593, both P<0.01). Conclusions 68Ga-PSMA-11 PET/CT could precisely detect both primary and metastatic lesions of CRPC, suggesting that it is of great value for the clinical management and treatment. Key words: Prostatic neoplasms, castration-resistant; Positron-emission tomography; Tomography, X-ray computed; Prostate-specific membrane antigen; Gallium radioisotopes

INDIVIDUALIZATION OF TREATMENT OF PATIENTS WITH CEREBRAL METASTASES OF MALIGNANT TUMORS. PROGNOSTIC SCALE TUNS

Improvement in the diagnosis and treatment of cancer patients, increase in frequency of prevalence and detection of metastatic lesions of the brain make the choice of treatment timely and important. The article presents data on the current prognostic scales for patients with cerebral metastases of solid tumors and the analysis of their features. The features of choice of tactics and strategy of treatment of patients with cerebral metastases of solid tumors depending on various prognostic factors are described. The original version of the rating scale for determining treatment options for patients with metastatic brain lesions is proposed. We suggest to consider oncological, neurological (neurosurgical), somatic (functional) groups of factors to choose the tactics of treatment of patients with brain metastases.

Pilot study: use of gallium-68 PSMA PET for detection of metastatic lesions in patients with renal tumour

BackgroundIn this study, we prospectively evaluate the diagnostic potential of a gallium-68 (68Ga) prostate-specific membrane antigen (PSMA)-binding ligand and positron emission tomography (PET) in detecting metastatic lesions in patients with renal tumour. The secondary aim was to determine whether the findings would result in the alteration of patient management.ResultsTen patients with renal lesion and potential metastatic disease on conventional imaging were recruited. Patients underwent PSMA PET in addition to standard imaging. Nine patients underwent nephrectomy and 4 patients underwent additional targeted biopsy to provide specimens for histopathological validation. There were 89 pathological lesions on CT, of which 32 were removed or biopsied for histopathological correlation. With PSMA PET, 86 PET avid lesions were identified with 36 samples being available for analysis. Thirty-five of 36 samples were positive for renal cell carcinoma deposits, whilst 1 sample was inconclusive for diagnosis on biopsy. For the histologically confirmed lesions, there were no false-negative PSMA PET lesions; however, CT was false negative in 11. In two patients, surgical strategies were changed based on PSMA PET findings.ConclusionsPSMA PET may potentially have a role in the preoperative staging of advanced renal cell carcinoma as PET detected multiple histologically proven metastatic lesions which were false negative on CT scanning, resulting in change in surgical strategies in some patients. We cautiously support a larger study to confirm these results and to assess the longitudinal impact on patient outcomes.Trial registrationAustralia and New Zealand Clinical Trial Registry (ANZCTR), ACTRN12615000854538.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-016-0231-6) contains supplementary material, which is available to authorized users.

Bottom up design of nanoparticles for anti-cancer diapeutics: “put the drug in the cancer’s food”

The story starts in Basel at CLINAM in 2013, when I asked Pieter about making nanoparticles and he advised me to “try this solvent-exchange method we have developed for making limit sized particles”. We are particularly interested in what are “limit size materials” because we want to test the feasibility of an idea: could we design, make, develop, and test the concept for treating metastatic cancer by, “Putting the Drug in the Cancer’s Food? “Limit size” is the size of the cancer‘s food, ? the common Low Density Lipoprotein, (LDL) ~20 nm diameter. In this contribution to Pieter’s LTAA we focus on the “bottom” (nucleation) and the “up” (growth) of “bottom-up design” as it applies to homogeneous nucleation of especially, hydrophobic drugs and the 8 physico-chemical stages and associated parameters that determine the initial size, and any subsequent coarsening, of a nanoparticle suspension. We show that, when made by the rapid solvent-exchange method, the same sized particles can be obtained without phospholipid. Furthermore, the obtained size follows the predictions of classic nucleation theory when the appropriate values for the parameters (surface tension and supersaturation) at nucleation are included. Calculations on dissolution time for nanoparticles reveal that a typical fewmicromolar-solubility, hydrophobic, anti-cancer drug (like Lapatinib, Niclosamide, Abiraterone, and Fulvestrant) of 500 nm diameter would take between 3?7 s to dissolve in an infinite sink like the blood stream; and a 50 nm particle would dissolve in less than a second! And so the nanoparticle design requires a highly water-insoluble drug, and a tight, encapsulating, impermeable lipid:cholesterol monolayer. While the “Y” junction can be used to mix an ethanolic solution with anti-solvent, we find that a “no-junction” can give equally good results. A series of nanoparticles (DiI-fluorescently labeled Triolein-cored and drug-cored nanoparticles of Orlistat) were then tested in well-characterized cell lines for uptake and efficacy as well as a PET-imageable nanoparticle in initial PET-imaging studies in animals for EPR uptake and tumor detection. We show that, while free-drug cannot be optimally administered in vivo, a nanoparticle formulation of orlistat could in principle represent a stable parenteral delivery system. The article ends with a brief discussion of what we see as the way forward in Individualized Medicine from the Diagnostic-Therapeutic (“Diapeutic”) side, requiring 18FDG detection of metastatic lesions, functional imaging of a protein target (e.g. Fatty Acid Synthase) using 11C acetate, then a PET (or other)-imageable nanoparticle to demonstrate EPR accumulation, and then the administration of the pure-drug nanoparticle taken in by the most aggressive cancer cells in the perivascular space, as they would their “food”.

PET/CT comparing (68)Ga-DOTATATE and other radiopharmaceuticals and in comparison with CT/MRI for the localization of sporadic metastatic pheochromocytoma and paraganglioma.

Pheochromocytomas/paragangliomas (PPGLs) and their metastases are tumors that predominantly express somatostatin receptor 2 (SSR2). (68)Ga-DOTA(0)-Tyr(3)-octreotate ((68)Ga-DOTATATE) is a PET radiopharmaceutical with both high and selective affinity for SSRs. The purpose of this study was to evaluate the utility of (68)Ga-DOTATATE in comparison with other specific and nonspecific radiopharmaceuticals recommended in the current guidelines for the localization of metastatic sporadic PPGL by PET/CT. This prospective study included 22 patients (15 men, 7 women; aged 50.0 ± 13.9years) with confirmed metastatic PPGL, a negative family history for PPGL, and negative genetic testing, who underwent (68)Ga-DOTATATE, (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) PET/CT, and CT/MRI. Only 12 patients underwent an additional (18)F-fluorodihydroxyphenylalanine ((18)F-FDOPA) PET/CT scan and only 11 patients underwent an additional (18)F-fluorodopamine ((18)F-FDA) PET/CT scan. The rates of detection of metastatic lesions were compared among all the imaging studies. A composite of all functional and anatomical imaging studies served as the imaging comparator. (68)Ga-DOTATATE PET/CT showed a lesion-based detection rate of 97.6% (95% confidence interval, CI, 95.8-98.7%). (18)F-FDG PET/CT, (18)F-FDOPA PET/CT, (18)F-FDA PET/CT, and CT/MRI showed detection rates of 49.2% (CI 44.5-53.6%; p < 0.01), 74.8% (CI 69.0-79.9%); p < 0.01), 77.7% (CI 71.5-82.8%; p < 0.01), and 81.6% (CI 77.8-84.8%; p < 0.01), respectively. The results of this study demonstrate the superiority of (68)Ga-DOTATATE PET/CT in the localization of sporadic metastatic PPGLs compared to all other functional and anatomical imaging modalities, and suggest modification of future guidelines towards this new imaging modality.