Imaging in interventional oncology, the better you see, the better you treat.

Imaging and image processing is the fundamental pillar of interventional oncology in which diagnostic, procedure planning, treatment and follow-up are sustained. Knowing all the possibilities that the different image modalities can offer is capital to select the most appropriate and accurate guidance for interventional procedures. Despite there is a wide variability in physicians preferences and availability of the different image modalities to guide interventional procedures, it is important to recognize the advantages and limitations for each of them. In this review, we aim to provide an overview of the most frequently used image guidance modalities for interventional procedures and its typical and future applications including angiography, computed tomography (CT) and spectral CT, magnetic resonance imaging, Ultrasound and the use of hybrid systems. Finally, we resume the possible role of artificial intelligence related to image in patient selection, treatment and follow-up.

Fc multimers effectively treat murine models of multiple sclerosis.

Multiple Sclerosis (MS) is a chronic neurodegenerative disease with limited therapeutic options. Recombinant Fc multimers (rFc), designed to mirror many of the anti-inflammatory activities of Intravenous Immunoglobulin (IVIG), have been shown to effectively treat numerous immune-mediated diseases in rodents. In this study we used the experimental autoimmune encephalomyelitis (EAE) murine model of MS to test the efficacy of a rFc, M019, that consists of multimers of the Fc portion of IgG2, in inhibiting disease severity. We show that M019 effectively reduced clinical symptoms when given either pre- or post-symptom onset compared to vehicle treated EAE induced mice. M019 was effective in reducing symptoms in both SJL model of relapsing remitting MS as well as the B6 model of chronic disease. M019 binds to FcγR bearing-monocytes both in vivo and in vitro and prevented immune cell infiltration into the CNS of treated mice. The lack of T cell infiltration into the spinal cord was not due to a decrease in T cell priming; there was an equivalent frequency of Th17 cells in the spleens of M019 and vehicle treated EAE induced mice. Surprisingly, there was an increase in chemokines in the sera but not in the CNS of M019 treated mice compared to vehicle treated animals. We postulate that M019 interacts with a FcγR rich monocyte intermediary to prevent T cell migration into the CNS and demyelination.

The Use of Intracardiac Echocardiography in Transjugular Intrahepatic Portosystemic Shunt Procedure.

Transjugular intrahepatic portosystemic shunt (TIPS) is a complex intervention with a steep learning curve that requires centers of expertise to improve technical success and reduce complications. Portal venous access is the most challenging step of the procedure and requires planning and image guidance strategies to prevent vascular or bile duct injury and further complications. Intracardiac echocardiography (ICE) has been reported to be a safe and accurate tool that provides images of the portal vein anatomy in real time. The use of ICE has become the standard of care in several centers. It is now frequently used to target the portal vein in complex TIPS procedures. This review article describes some technical aspects and indications of ICE-guided TIPS.

PSMA-Targeting Imaging and Theranostic Agents-Current Status and Future Perspective.

In the past two decades, extensive efforts have been made to develop agents targeting prostate-specific membrane antigen (PSMA) for prostate cancer imaging and therapy. To date, represented by two recent approvals of [68Ga]Ga-PSMA-11 and [18F]F-DCFPyL by the United States Food and Drug Administration (US-FDA) for positron emission tomography (PET) imaging to identify suspected metastases or recurrence in patients with prostate cancer, PSMA-targeting imaging and theranostic agents derived from small molecule PSMA inhibitors have advanced to clinical practice and trials of prostate cancer. The focus of current development of new PSMA-targeting agents has thus shifted to the improvement of in vivo pharmacokinetics and higher specific binding affinity with the aims to further increase the detection sensitivity and specificity and minimize the toxicity to non-target tissues, particularly the kidneys. The main strategies involve systematic chemical modifications of the linkage between the targeting moiety and imaging/therapy payloads. In addition to a summary of the development history of PSMA-targeting agents, this review provides an overview of current advances and future promise of PSMA-targeted imaging and theranostics with focuses on the structural determinants of the chemical modification towards the next generation of PSMA-targeting agents.

Thyroid Cancer Bone Metastasis: Survival and Genomic Characteristics of a Large Tertiary Care Cohort.

Bone metastasis (BM) in differentiated thyroid cancer (DTC) is the second most common site of metastasis after lung. Bone metastases are associated with worse prognosis in DTC. In this study, we examined risk factors for overall survival in patients with BM and for the first time explore the pattern of genomic alterations in DTC BM. PATIENTS AND METHODS: A Health Insurance Portability and Accountability Act (HIPAA) compliant, institutional review board-approved retrospective evaluation of the medical record was performed for all patients treated at a single institution for thyroid cancer over a 16-year period. Seventy-four patients met inclusion criteria. Multiple prognostic factors including age, sex, genes, radioactive iodine, and radiation or kinase inhibitor therapies were analyzed. Univariate and multivariate analyses were performed. RESULTS: Treatment with external beam radiation was found to significantly increase survival (P = 0.03). The 5-year survival rate was 59% and median survival was 92 months. Patients who developed bone metastasis earlier tend to live longer (P = 0.06). The presence of TERT and BRAF mutations did not significantly worsen the prognosis (P = 0.10). CONCLUSION: Patients with DTC can benefit from early treatment with external beam radiation therapy, especially those who develop bone metastasis within 3 years of primary TC diagnosis. Kinase inhibitor treatment tended to prolong survival but not in a statistically significant manner. Sex, age, and TERT or BRAF genetic mutations did not significantly affect the prognosis.

Thyroid Cancer Brain Metastasis: Survival and Genomic Characteristics of a Large Tertiary Care Cohort.

PURPOSE: Brain metastases (BMs) in patients with differentiated thyroid cancer (DTC) are rare but associated with poor prognosis. We examined risk factors for overall survival (OS) in this population and explored the pattern of genomic alterations. METHODS: Single-institution, retrospective review of all patients with DTC from January 2000 to November 2016 identified 79 patients for analysis. Multiple prognostic factors, including age, gender, distal metastasis (DM), diagnosis time, DM sites, BM diagnosis time, BM number and size, genomic sequencing data, craniectomy, external beam radiation therapy, and kinase inhibitor therapies, were evaluated. Univariate and multivariate analyses were performed. RESULTS: Median survival after BM was 18 months. One- and 3-year survival rates were 63% and 33%, respectively. Univariate analysis identified 4 covariates correlated with prolonged survival: time between DTC diagnosis and BM for less than 3 years (P = 0.01), time from initial DM diagnosis to BM for 22 months or less (P = 0.03), 3 BM sites or fewer (P = 0.002), and craniectomy (P = 0.05). Multivariate model revealed 3 variables associated with OS: DTC diagnosis to BM time of less than 3 years (P = 0.04), craniectomy (P = 0.06), and patients with fewer than 3 BM sites (P = 0.06). The majority of patients with BM had a telomerase reverse transcriptase promoter mutation, However, mutational status was not an independent predictor of survival. CONCLUSIONS: For BM from DTC, time interval between DTC diagnosis and BM, number of BM sites, and craniectomy were independently associated with OS. Further studies are needed to define the role of genomic mutations in advanced cancer.

Cancer Health Impact Program (CHIP): Identifying Social and Demographic Associations of mHealth Access and Cancer Screening Behaviors Among Brooklyn, New York, Residents.

BACKGROUND: The Bedford-Stuyvesant (BS) and Bushwick (BW) communities of central Brooklyn, New York, are located within the 50-mile core radius of Memorial Sloan Kettering's main catchment area. Cancer is the second leading cause of death among the predominantly African American and Hispanic neighborhoods, with BS and BW having higher prostate cancer and colorectal mortality rates than New York City as a whole. There is significant opportunity to design cancer interventions that leverage the accessibility and acceptability of mobile health (mHealth) tools among the BS and BW communities. METHODS: The Cancer Health Impact Program (CHIP) is a collaborative that was formed for this purpose. Through CHIP, we used a tablet-based, Health Information National Trends (HINTS)-based multimodality survey to collect and analyze social and demographic patterns of prostate cancer and colorectal cancer screening, as well as mHealth access, among BS and BW residents. RESULTS: Among 783 participants, 77% reported having a smartphone, 40% reported access to a mobile health application, 17% reported blood stool kit testing, and 26% of men reported PSA test screening. Multivariable logistic regression models results demonstrated that participants who reported owning smartphones, but were unsure whether they had access to a health app, were also significantly more likely to report blood stool kit testing compared with participants without smartphones. In fully adjusted models, access to a health app was not significantly associated with PSA testing. Non-Hispanic white participants were 86% less likely to report blood stool kit testing when compared with non-Hispanic black participants [OR = 0.15; 95% confidence interval (CI) 0.02-0.49]. Participants with a prior history of cancer were three times more likely to report blood stool kit testing when compared with those without cancer history (OR = 3.18; 95% CI, 1.55-6.63). CONCLUSIONS: For blood stool kit testing, significant differences were observed by race/ethnicity, cancer history, age, and smartphone use; for PSA screening, only age was significant in fully adjusted models. IMPACT: Our results demonstrate that while access to smartphones and mobile health apps may be prevalent among minority communities, other social and demographic characteristics are more likely to influence screening behaviors.

DAXX Mutation Status of Embolization-Treated Neuroendocrine Tumors Predicts Shorter Time to Hepatic Progression.

PURPOSE: To identify common gene mutations in patients with neuroendocrine liver metastases (NLM) undergoing transarterial embolization (TAE) and establish relationship between these mutations and response to TAE. MATERIALS AND METHODS: Patients (n = 51; mean age 61 y; 29 men, 22 women) with NLMs who underwent TAE and had available mutation analysis were identified. Mutation status and clinical variables were recorded and evaluated in relation to hepatic progression-free survival (HPFS) (Cox proportional hazards) and time to hepatic progression (TTHP) (competing risk proportional hazards). Subgroup analysis of patients with pancreatic NLM was performed using Fisher exact test to identify correlation between mutation and event (hepatic progression or death) by 6 months. Changes in mutation status over time and across specimens in a subset of patients were recorded. RESULTS: Technical success of TAE was 100%. Common mutations identified were MEN1 (16/51; 31%) and DAXX (13/51; 25%). Median overall survival was 48.7 months. DAXX mutation status (hazard ratio = 6.21; 95% confidence interval [CI], 2.67-14.48; P < .001) and tumor grade (hazard ratio = 3.05; 95% CI, 1.80-5.17; P < .001) were associated with shorter HPFS and TTHP on univariate and multivariate analysis. Median HPFS was 3.6 months (95% CI, 1.7-5.3) for patients with DAXX mutation compared with 8.9 months (95% CI, 6.6-11.4) for patients with DAXX wild-type status. In patients with pancreatic NLMs, DAXX mutation status was associated with hepatic progression or death by 6 months (P = .024). DAXX mutation status was concordant between primary and metastatic sites. CONCLUSIONS: DAXX mutation is common in patients with pancreatic NLMs. DAXX mutation status is associated with shorter HPFS and TTHP after TAE.

Percutaneous Embolization of a Pulmonary Vein Pseudoaneurysm Secondary to Vascular Erosion of a Metastatic Mass.

Fifty-two-year-old female with high-grade undifferentiated pleomorphic left thigh sarcoma and bilateral metastatic soft tissue lesions to the lungs consistent with metastases, presented with recurrent, anemia, and worsening hemoptysis. Cross-sectional imaging demonstrated erosion of a right lower lobe metastatic mass into an adjacent right inferior lower lobe pulmonary vein with formation of a pseudoaneurysm. We report the successful treatment of this pseudoaneurysm via direct image-guided percutaneous access with subsequent coil embolization.

Clinical PET-MR Imaging in Breast Cancer and Lung Cancer.

Hybrid imaging systems have dramatically improved thoracic oncology patient care over the past 2 decades. PET-MR imaging systems have the potential to further improve imaging of thoracic neoplasms, resulting in diagnostic and therapeutic advantages compared with current MR imaging and PET-computed tomography systems. Increasing soft tissue contrast and lesion sensitivity, improved image registration, reduced radiation exposure, and improved patient convenience are immediate clinical advantages. Multiparametric quantitative imaging capabilities of PET-MR imaging have the potential to improve understanding of the molecular mechanisms of cancer and treatment effects, potentially guiding improvements in diagnosis and therapy.

Isotopic evidence indicates saprotrophy in post-fire Morchella in Oregon and Alaska.

We assessed the nutritional strategy of true morels (genus Morchella) collected in 2003 and 2004 in Oregon and Alaska, 1 or 2 y after forest fires. We hypothesized that the patterns of stable isotopes (δ(13)C and δ(15)N) in the sporocarps would match those of saprotrophic fungi and that radiocarbon (Δ(14)C) analyses would indicate that Morchella was assimilating old carbon not current-year photosynthate. We compared radiocarbon and stable isotopes in Morchella with values from concurrently collected foliage, the ectomycorrhizal Geopyxis carbonaria (Alb. & Schwein.) Sacc., the saprotrophic Plicaria endocarpoides (Berk.) Rifai, and with literature to determine isotopic values for ectomycorrhizal or saprotrophic fungi. Geopyxis, Plicaria and Morchella, respectively, were 3‰, 5‰ and 6‰ higher in 13C than foliage and 5‰, 7‰ and 7‰ higher in (15)N. High (15)N enrichment in Morchella indicated that recent litter was not the primary source for Morchella nitrogen, and similar (13)C and (15)N enrichments to Plicaria suggest that Morchella assimilates its carbon and nitrogen from the same source pool as this saprotrophic fungus. From radiocarbon analyses Morchella averaged 11 ± 6 y old (n = 19), Plicaria averaged 17 ± 5 y old (n = 3), foliage averaged 1 ± 2 y old (n = 8) and Geopyxis (n = 1) resembled foliage in Δ(14)C. We conclude that morels fruiting in post-fire environments in our study assimilated old carbon and were saprotrophic.

Association between changes in suspicious prostate lesions on serial MRI examinations and follow-up biopsy results.

We assessed changes in prostate lesions on serial magnetic resonance imaging (MRI) examinations in predicting biopsy results. Fifty-five men undergoing two prostate MRI examinations ≥6 months apart, followed by targeted biopsy, were included. Two radiologists assessed dominant lesions for an increase in size or suspicion score. Progression on MRI had lower sensitivity (23.5%-35.3%) and higher specificity (76.2%-90.5%) than prostate-specific antigen (PSA) velocity (sensitivity 70.6%, specificity 52.4%) for predicting positive biopsy. Highest accuracy was achieved by PSA velocity (63.6%) for positive biopsy, and by MRI (65.5%-72.7%) for Gleason >6 tumor. Findings support lesion progression on MRI serving as a basis for performing subsequent targeted biopsy.

Proximal anastomosis using the OrVil circular stapler in major upper gastrointestinal surgery.

Anastomoses in major upper gastrointestinal surgery can be technically demanding, especially handsewn anastomoses traversing the diaphragmatic hiatus. The OrVil stapler is a unique circular stapler that allows rapid creation of various upper gastrointestinal anastomoses in technically challenging circumstances, particularly if additional proximal clearance is desirable. Little is reported in the literature regarding its outcomes and complication rates. In this 'How I do It' article, we describe our technique and experience with the OrVil in major upper gastrointestinal surgery.

Endothelial injury markers before and after nasal continuous positive airway pressure treatment for obstructive sleep apnoea hypopnoea syndrome.

PURPOSE: The purpose of this study was to evaluate whether serum amyloid A (SAA), C-reactive protein (CRP), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) levels are elevated in obstructive sleep apnoea hypopnoea syndrome (OSAHS), and whether they change following acute- and medium-term CPAP treatment. METHODS: Consecutive subjects (n = 40) referred to the Sleep Disordered Breathing Unit were included in the research. Sera were sampled in the afternoon prior to an in-hospital limited-channel sleep study and on the next morning. Those diagnosed with OSAHS were commenced on CPAP and had further blood samples collected in the morning after the first night and then after a month of treatment. RESULTS: We had 20 subjects with moderate/severe OSAHS (mean ± SD), 4% desaturation rate (4% DR) 44.3 ± 31.4 events/h, and 20 comparator subjects with symptoms but negative sleep studies, 4% DR 5.6 ± 2.9 events/h. There was no difference in the morning and afternoon vascular injury marker levels between the OSAHS and comparator groups. However, CRP (6.52 ± 9.53 vs. 5.58 ± 8.47, p = 0.04) and VCAM-1 (366.30 ± 90.11 vs. 339.60 ± 95.87, p = 0.02) levels showed significant diurnal variation within the OSAHS group with higher afternoon levels compared to morning measurements. There were no changes in any of the vascular injury marker levels following CPAP. CONCLUSIONS: This study demonstrates that OSAHS leads to endothelial dysfunction as reflected by higher afternoon than morning CRP and VCAM-1 levels. However, despite a good CPAP compliance, a month of treatment does not decrease vascular injury marker levels.

Applying PET to broaden the diagnostic utility of the clinically validated CA19.9 serum biomarker for oncology.

UNLABELLED: Despite their considerable advantages, many circulating biomarkers have well-documented limitations. One prominent shortcoming in oncology is a high frequency of false-positive indications for malignant disease in upfront diagnosis. Because one common cause of false positivism is biomarker production from benign disorders in unrelated host tissues, we hypothesized that probing the sites of biomarker secretion with an imaging tool could be a broadly useful strategy to deconvolute the meaning of foreboding but inconclusive circulating biomarker levels. METHODS: In preparation to address this hypothesis clinically, we developed (89)Zr-5B1, a fully human, antibody-based radiotracer targeting tumor-associated CA19.9 in the preclinical setting. RESULTS: (89)Zr-5B1 localized to multiple tumor models representing diseases with undetectable and supraphysiologic serum CA19.9 levels. Among these, (89)Zr-5B1 detected orthotopic models of pancreatic ductal adenocarcinoma, an elusive cancer for which the serum assay is measured in humans but with limited specificity in part because of the frequency of CA19.9 secretion from benign hepatic pathologies. CONCLUSION: In this report, a general strategy to supplement some of the shortcomings of otherwise highly useful circulating biomarkers with immunoPET is described. To expedite the clinical validation of this model, a human monoclonal antibody to CA19.9 (a highly visible but partially flawed serum biomarker for several cancers) was radiolabeled and evaluated, and the compelling preclinical evidence suggests that the radiotracer may enhance the fidelity of diagnosis and staging of pancreatic ductal adenocarcinoma, a notoriously occult cancer.

Imaging tumor burden in the brain with 89Zr-transferrin.

UNLABELLED: A noninvasive technology that indiscriminately detects tumor tissue in the brain could substantially enhance the management of primary or metastatic brain tumors. Although the documented molecular heterogeneity of diseases that initiate or eventually deposit in the brain may preclude identifying a single smoking-gun molecular biomarker, many classes of brain tumors are generally avid for transferrin. Therefore, we reasoned that applying a radiolabeled derivative of transferrin ((89)Zr-labeled transferrin) may be an effective strategy to more thoroughly identify tumor tissue in the brain, regardless of the tumor's genetic background. METHODS: Transferrin was radiolabeled with (89)Zr, and its properties with respect to human models of glioblastoma multiforme were studied in vivo. RESULTS: In this report, we show proof of concept that (89)Zr-labeled transferrin ((89)Zr-transferrin) localizes to genetically diverse models of glioblastoma multiforme in vivo. Moreover, we demonstrate that (89)Zr-transferrin can detect an orthotopic lesion with exceptional contrast. Finally, the tumor-to-brain contrast conferred by (89)Zr-transferrin vastly exceeded that observed with (18)F-FDG, currently the most widely used radiotracer to assess tumor burden in the brain. CONCLUSION: The results from this study suggest that (89)Zr-transferrin could be a broadly applicable tool for identifying and monitoring tumors in the brain, with realistic potential for near-term clinical translation.

Annotating MYC status with 89Zr-transferrin imaging.

A noninvasive technology that quantitatively measures the activity of oncogenic signaling pathways could have a broad impact on cancer diagnosis and treatment with targeted therapies. Here we describe the development of (89)Zr-desferrioxamine-labeled transferrin ((89)Zr-transferrin), a new positron emission tomography (PET) radiotracer that binds the transferrin receptor 1 (TFRC, CD71) with high avidity. The use of (89)Zr-transferrin produces high-contrast PET images that quantitatively reflect treatment-induced changes in MYC-regulated TFRC expression in a MYC-driven prostate cancer xenograft model. Moreover, (89)Zr-transferrin imaging can detect the in situ development of prostate cancer in a transgenic MYC prostate cancer model, as well as in prostatic intraepithelial neoplasia (PIN) before histological or anatomic evidence of invasive cancer. These preclinical data establish (89)Zr-transferrin as a sensitive tool for noninvasive measurement of oncogene-driven TFRC expression in prostate and potentially other cancers, with prospective near-term clinical application.

Early assessment of radiation response using a novel functional imaging modality -- [18F]fluorocholine PET (FCH-PET): a pilot study.

AIM: [¹8F]Fluorodeoxyglucose-positron emission tomography/computerized tomography (FDG-PET) is commonly used to assess response to patients treated with radiation (RT) or combination of chemotherapy and RT (CRT). The intent of this pilot study is to explore whether [¹8F]fluorocholine PET (FCH-PET) can serve as an early predictive biomarker for early detection of RT/CRT response. MATERIALS AND METHODS: Fourteen patients have been accrued and analyzed. The lesions were base of tongue, tonsil, nodes, hypopharynx, maxilla, palate, lung, pancreas, brain, uterine, and rectal. There were 16 lesions that were considered target lesion and were followed for correlation between change in FCH-PET SUVmax readings and clinical outcome. Median tumor size was 4.4 cm. Median RT dose was 66 Gy. The change in SUVmax (Δ SUVmax) of FCH-PET scans performed before and during RT was correlated with clinical outcome at the last follow-up. RESULTS: The median FCH-PET SUVmax for the 1st and 2nd scans was 6.15 and 4.65, respectively. Fourteen (87.5%) lesions showed a reduction in SUVmax in either a complete response (CR) or a partial response (PR), and 2 lesions showed an increase in SUVmax both of which were determined to be non-response (NR). The median percentage change between the 1st and 2nd scan was -19.5%. Forty-four percent of lesions (7/16) had CR, 44% (7/16) had PR, and 12% (2/16) had NR (no response). Median follow-up was 12 months. The results showed a difference between NR and PR, between NR and CR, and a trend towards significance (p=0.06). CONCLUSION: FCH-PET scan demonstrated changes in SUVmax during RT that were predictive of final outcome.

Imaging androgen receptor signaling with a radiotracer targeting free prostate-specific antigen.

UNLABELLED: Despite intense efforts to develop radiotracers to detect cancers or monitor treatment response, few are widely used as a result of challenges with demonstrating clear clinical use. We reasoned that a radiotracer targeting a validated clinical biomarker could more clearly assess the advantages of imaging cancer. The virtues and shortcomings of measuring secreted prostate-specific antigen (PSA), an androgen receptor (AR) target gene, in patients with prostate cancer are well documented, making it a logical candidate for assessing whether a radiotracer can reveal new (and useful) information beyond that conferred by serum PSA. Therefore, we developed (89)Zr-labeled 5A10, a novel radiotracer that targets "free" PSA. (89)Zr-5A10 localizes in an AR-dependent manner in vivo to models of castration-resistant prostate cancer, a disease state in which serum PSA may not reflect clinical outcomes. Finally, we demonstrate that (89)Zr-5A10 can detect osseous prostate cancer lesions, a context where bone scans fail to discriminate malignant and nonmalignant signals. SIGNIFICANCE: This report establishes that AR-dependent changes in PSA expression levels can be quantitatively measured at tumor lesions using a radiotracer that can be rapidly translated for human application and advances a new paradigm for radiotracer development that may more clearly highlight the unique virtues of an imaging biomarker.