ABSTRACT
BACKGROUND: To investigate the sensitivity and specificity of 99mTc-HMPAO-leukocyte imaging in evaluating therapy result in patients with prosthetic joint infection (PJI) and in diagnosing suspected chronic PJI. METHODS: Sixty-two patients (63 joints) with microbiologically verified PJI were examined by leukocyte imaging to evaluate therapy result during or at the end of antibiotic treatment or if the patient had a chronic PJI after treatment. Group 1 consisted of 49 patients with on-going or within less than 14 days of ending antibiotic treatment examined to evaluate response. Group 2 consisted of 13 patients examined after completed treatment on suspicion of chronic PJI with no or recently initiated renewed antibiotic treatment. This study applied a combination of different imaging approaches of 99mTc-HMPAO-leukocyte scintigraphy: delayed and late planar images, bone marrow imaging and SPECT/CT imaging. All joints were examined with at least two of the approaches and 53 joints with all three approaches. The report was based on the combined results of the approaches used. A chronic PJI was confirmed with a positive microbiological culture. A cured infection was confirmed with either a negative culture or at least 24 months antibiotic-free follow-up with no relapse. RESULTS: In the therapy evaluation group sensitivity was 0.57 and specificity was 0.81. In the suspected chronic infection group sensitivity was 1.00 and specificity 0.91. CONCLUSIONS: 99mTc-HMPAO-leukocyte imaging appears to be an accurate method to diagnose or exclude chronic PJI, but cannot be recommended for therapy evaluation of PJI in patients with on-going antibiotic treatment.
Subject(s)
Joint Diseases/diagnostic imaging , Joint Diseases/drug therapy , Leukocytes/cytology , Prosthesis-Related Infections/diagnostic imaging , Prosthesis-Related Infections/drug therapy , Technetium Tc 99m Exametazime , Aged , Anti-Bacterial Agents/therapeutic use , Chronic Disease , Cohort Studies , Female , Humans , Image Processing, Computer-Assisted , Male , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Antenatally diagnosed urinary tract dilatation (UTD) still burdens healthcare providers and parents. This study was conducted to establish long-term outcome in an unselected group of children with antenatally detected UTD. METHODS: Seventy-one out of 103 children born in 2003-2005 and diagnosed with antenatal UTD agreed to participate in a 12-15-year follow-up including blood and urine samples, a kidney ultrasound exam, and kidney scintigraphy. The records were searched for previous urinary tract infections. RESULTS: Among children with an anteroposterior diameter (APD) ≤ 7 mm and no calyceal, kidney, ureteral, or bladder pathology in the early postnatal period, no one tested had reduced estimated glomerular filtration rate (eGFR), albuminuria, or UTD at the follow-up at a mean age of 13.6 years. One child had kidney damage not affecting kidney function. Among children with postnatal APD > 7 mm and/or kidney, calyceal, ureteral, or bladder pathology, 15% had persistent UTD and 32-39% (depending on the method used) had kidney damage. Major postnatal urinary tract ultrasound abnormalities and a congenital anomalies of the kidney and urinary tract (CAKUT) diagnosis were factors associated with an increased risk for permanent kidney damage (odds ratios 8.9, p = 0.016; and 14.0, p = 0.002, respectively). No one had reduced eGFR. One child (1/71, 1%) had a febrile urinary tract infection after the age of 2. CONCLUSIONS: We conclude that in children with postnatal APD ≤ 7 mm, no calyceal dilatation, normal bladder, ureters, and kidney parenchyma, the outcome is excellent. There is no need for long-term follow-up in these patients.
Subject(s)
Dilatation, Pathologic/congenital , Urinary Tract/abnormalities , Adolescent , Case-Control Studies , Cohort Studies , Dilatation, Pathologic/diagnostic imaging , Dilatation, Pathologic/pathology , Disease Progression , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Hydronephrosis/diagnostic imaging , Hydronephrosis/pathology , Male , Prenatal Diagnosis , Ultrasonography , Urinary Tract/diagnostic imaging , Urinary Tract/pathologyABSTRACT
BACKGROUND: Post hepatectomy liver failure (PHLF) after ALPPS has been related to the discrepancy between liver volume and function. Pre-operative hepatobiliary scintigraphy (HBS) can predict post-operative liver function and guide when it is safe to proceed with major hepatectomy. Aim of this study was to evaluate the role of HBS in predicting PHLF after ALPPS, defining a safe cut-off. METHODS: A multicenter retrospective study was approved by the ALPPS Registry. All patients selected for ALPPS between 2012 and 2018, were evaluated. Every patient underwent HBS during ALPPS evaluation. PHLF was reported according to ISGLS definition, considering grade B or C as clinically significant. RESULTS: 98 patients were included. Thirteen patients experienced PHLF grade B or C (14%) following ALPPS-2. The HBS and the daily gain in volume (KGRFLR) of the future liver remnant (FLR) were significantly lower in PHLF B and C (p = .004 and .041 respectively). ROC curves indicated safe cut-offs of 4.1%/day (AUC = 0.68) for KGRFLR, and of 2.7 %/min/m2 (AUC = 0.75) for HBSFLR. Multivariate analysis confirmed these cut-offs as variables predicting PHLF after ALPPS-2. CONCLUSION: Patients presenting a KGRFLR ≤4.1%/day and a HBSFLR ≤2.7%/min/m2 are at high risk of PHLF and their second stage should be re-discussed.
Subject(s)
Liver Failure , Liver Neoplasms , Hepatectomy/adverse effects , Humans , Liver/diagnostic imaging , Liver/surgery , Liver Failure/diagnostic imaging , Liver Failure/etiology , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Portal Vein/diagnostic imaging , Portal Vein/surgery , Radionuclide Imaging , Retrospective StudiesABSTRACT
Aim: Doxorubicin-eluting beads transarterial chemoembolization (DEB-TACE) is reported to improve survival and tolerability when compared with conventional lipiodol-TACE (cTACE) for the treatment of hepatocellular carcinoma (HCC). The aim of this study was to evaluate tolerability and long-term survival in patients treated with cTACE or DEB-TACE in a real-life setting. Methods: Incidence of adverse events and overall survival in HCC patients treated with either cTACE or DEB-TACE at Karolinska University Hospital 2004-2012 were analyzed retrospectively. Median follow-up was 7.1 years. Patients were censored when transplanted or at the end of follow-up. Patients receiving both cTACE and DEB-TACE, or treated with resection or ablation post-TACE were excluded from the survival analysis. Results: A total of 202 patients (76 cTACE and 126 DEB-TACE) were eligible for analysis of adverse events, and 179 patients (69 cTACE and 110 DEB-TACE) were included in the survival analysis. cTACE patients were younger and had fewer tumors but higher BCLC stage than DEB-TACE. Child-Pugh and ECOG performance status were similar between groups. Adverse events (abdominal pain, nausea and vomiting, fever, fatigue) were significantly less common in the DEB-TACE group. Median survival was 17.1 months in the cTACE group and 19.1 months in the DEB-TACE (NS). In multivariate Cox regression analysis, portal vein thrombosis and tumor size were associated with increased, and sorafenib treatment post-TACE with decreased mortality. Conclusion: In this retrospective real-life analysis, DEB-TACE had better tolerability compared to cTACE, but overall survival did not differ between the two treatments. Portal vein thrombosis, tumor size and sorafenib treatment after TACE influence survival.
Subject(s)
Carcinoma, Hepatocellular/drug therapy , Chemoembolization, Therapeutic/methods , Ethiodized Oil/administration & dosage , Liver Neoplasms/drug therapy , Microspheres , Aged , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/therapeutic use , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Drug Delivery Systems , Female , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Multivariate Analysis , Retrospective Studies , Sorafenib/administration & dosage , Sorafenib/therapeutic use , Survival Analysis , Treatment Outcome , Venous Thrombosis/etiologyABSTRACT
BACKGROUND: In most parts of the world, curatively intended treatment for esophageal cancer includes neoadjuvant therapy, either with chemoradiotherapy or chemotherapy alone, followed by esophagectomy. Currently 18F-FDG positron emission tomography/computed tomography (PET/CT) is used for preoperative disease staging, but is not well established in the evaluation of neoadjuvant treatment. PURPOSE: To evaluate changes in PET parameters in relation to the histological primary tumor response in the surgical specimen in patients randomized to neoadjuvant chemoradiotherapy or chemotherapy. MATERIAL AND METHODS: Patients were randomized between either neoadjuvant chemotherapy or chemoradiotherapy followed by esophagectomy.18F-FDG PET/CT exams were conducted at baseline and following neoadjuvant treatment. Standardized uptake ratio (SUR) values were measured in the primary tumor and compared as regards histological responders and non-responders as well as different treatment arms. RESULTS: Seventy-nine patients were enrolled and 51 were available for analysis. A significant rate of SUR reduction was observed ( P = 0.02) in the primary tumor in histological responders compared to non-responders. Changes in SUR were significantly greater in responders following chemoradiotherapy ( P = 0.02), but not following chemotherapy alone ( P = 0.49). There was no statistically significant difference in SUR in patients with a complete histological response compared to those with a subtotal response. CONCLUSION: Our results are similar to those of previous studies and show that changes in the rate of SUR can be used reliably to differentiate histological responders from non-responders after neoadjuvant treatment with either chemoradiotherapy or chemotherapy. Limitations of current PET technology are likely to restrict the possibility of accurately ruling out limited residual disease.
Subject(s)
Esophageal Neoplasms/therapy , Fluorodeoxyglucose F18 , Neoadjuvant Therapy/methods , Positron Emission Tomography Computed Tomography/methods , Radiopharmaceuticals , Adult , Aged , Esophagogastric Junction/diagnostic imaging , Esophagus/diagnostic imaging , Female , Humans , Male , Middle Aged , Norway , SwedenABSTRACT
PURPOSE: The timing of sentinel lymph node biopsy (SLNB) in the context of neoadjuvant systemic therapy (NAST) in breast cancer is still controversial. SLNB before NAST has been evaluated in few single-institution studies in which axillary lymph node dissection (ALND), however, was commonly not performed in case of a negative SLNB. We investigated the potential clinical relevance of SLNB before NAST by performing ALND in all patients after NAST. METHODS: This national multicenter trial prospectively enrolled clinically node-negative breast cancer patients planned for NAST at 13 recruiting Swedish hospitals between October 2010 and December 2015. SLNB before NAST was followed by ALND after NAST in all individuals. Repeat SLNB after NAST was encouraged but not mandatory. RESULTS: SLNB before NAST was performed in 224 patients. The identification rate was 100% (224/224). The proportion of patients with a negative SLNB before NAST but positive axillary lymph nodes after NAST was 7.4% (nine of 121 patients, 95% CI 4.0-13.5). Among those with a positive SLNB before NAST, 23.2% (86/112) had further positive lymph nodes after NAST. CONCLUSIONS: In clinically node-negative patients, SLNB before NAST is highly reliable. With this sequence, ALND and regional radiotherapy can be safely omitted in patients with a negative SLNB provided good clinical response to NAST. Additionally, SLNB-positive patients upfront will receive correct nodal staging unaffected by NAST and be consequently offered adjuvant locoregional treatment according to current guidelines pending the results of ongoing randomized trials.
Subject(s)
Breast Neoplasms/pathology , Breast Neoplasms/therapy , Lymph Node Excision/methods , Sentinel Lymph Node Biopsy/methods , Adult , Aged , Axilla , Female , Humans , Mastectomy , Middle Aged , Neoadjuvant Therapy , Prospective Studies , Radiotherapy , Sensitivity and Specificity , Sweden , Young AdultABSTRACT
PURPOSE: Patients with clinically node-positive breast cancer planned for neoadjuvant systemic therapy (NAST) may draw advantages from the nodal downstaging effect and reduce the extent of axillary surgery with sentinel lymph node biopsy (SLNB) performed after NAST. Since there are concerns about lower sentinel lymph node (SLN) detection and higher false-negative rates (FNR) in this setting, our aim was to define the accuracy of SLNB after NAST. METHODS: This Swedish national multicenter trial prospectively recruited 195 breast cancer patients from ten hospitals with T1-T4d biopsy-proven node-positive disease planned for NAST between October 1, 2010 and December 31, 2015. Clinically node-negative axillary status after NAST was not mandatory. SLNB was always attempted and followed by a completion axillary lymph node dissection (ALND). RESULTS: The SLN identification rate was 77.9% (152/195) but improved to 80.7% (138/171) with dual mapping. The median number of SLNs was two (range 1-5). A positive SLNB was found in 52% (79/152), almost 66% (52/79) of whom had additional positive non-sentinel lymph nodes. The overall pathologic nodal response rate was 33.3% (66/195). The overall FNR was 14.1% (13/92) but decreased to 4% (2/50) when only patients with two or more sentinel nodes were analyzed. CONCLUSIONS: In biopsy-proven node-positive breast cancer, SLNB after NAST is feasible even though the identification rate is lower than in clinically node-negative patients. Since the overall FNR is unacceptably high, the omission of ALND should only be considered if two or more SLNs are identified.
Subject(s)
Anthracyclines/therapeutic use , Aromatase Inhibitors/therapeutic use , Breast Neoplasms/therapy , Mastectomy/methods , Sentinel Lymph Node Biopsy/methods , Taxoids/therapeutic use , Adult , Aged , Aged, 80 and over , Axilla , Female , Humans , Lymph Node Excision/methods , Lymphatic Metastasis , Middle Aged , Neoadjuvant Therapy , Prospective Studies , Sensitivity and Specificity , SwedenABSTRACT
Doxorubicin (DOX) delivered in a lipiodol-based emulsion (LIPDOX) or in drug-eluting beads (DEBDOX) is used as palliative treatment in patients with intermediate-stage hepatocellular carcinoma (HCC). The primary objective of this study was to evaluate the in vivo delivery performance of DOX from LIPDOX or DEBDOX in HCC patients using the local and systemic pharmacokinetics of DOX and its main metabolite doxorubicinol (DOXol). Urinary excretion of DOX and DOXol and their short-term safety and antitumor effects were also evaluated. In this open, prospective, nonrandomized multicenter study, LIPDOX (n = 13) or DEBDOX (n = 12) were injected into the feeding arteries of the tumor. Local (vena cava/hepatic vein orifice) and systemic (peripheral vein) plasma concentrations of DOX and DOXol were determined in samples obtained up to 6 h and 7 days after treatment. Tumor response was assessed using computed tomography or magnetic resonance imaging. The Cmax and AUC0-24 h for DOX were 5.6-fold and 2.4-fold higher in LIPDOX vs DEBDOX recipients, respectively (p < 0.001). After 6 h, the respective mean proportions of the dose remaining in the liver or drug-delivery system (DDS) were 49% for LIPDOX and 88% for DEBDOX. LIPDOX releases DOX faster than DEBDOX in HCC patients and provides more extensive local and systemic exposure (AUC) to DOX and DOXol initially (0-7 days). DEBDOX formulation has a release and distribution of DOX that is more restricted and rate controlled than LIPDOX.
Subject(s)
Antibiotics, Antineoplastic/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Emulsions/therapeutic use , Ethiodized Oil/therapeutic use , Liver Neoplasms/drug therapy , Aged , Aged, 80 and over , Drug Delivery Systems/methods , Female , Humans , Liver/drug effects , Male , Middle Aged , Prospective StudiesABSTRACT
PURPOSE: To prospectively assess feasibility, safety, and cytoreductive effect of transarterial chemoembolization on renal cell carcinoma (RCC) using drug-eluting embolic agent (DEE) saturated with doxorubicin compared with transarterial embolization (TAE). MATERIALS AND METHODS: Between 2012 and 2015, 12 patients (male/female = 5/7, age 66 y ± 9.8) with biopsy-verified RCC eligible for nephron-sparing surgery or radical nephrectomy were recruited. Mean tumor size was 3.2 cm ± 0.62. Patients were randomized at 1:1 ratio to receive either DEE transarterial chemoembolization or TAE before planned surgery. A microcatheter was used to inject particles selectively into arteries feeding the tumors. Response was evaluated by CT according to modified Response Evaluation Criteria In Solid Tumors and by microscopy of excised tumors. Complications were scored according to the Society of Interventional Radiology classification. RESULTS: DEE transarterial chemoembolization (n = 6) resulted in a significantly (P = .018) higher degree of necrosis with an average of 88.3% (range, 70%-100%) compared with TAE (n = 5), which resulted in an average of 29.4% (range, 0-77%), as evaluated by CT. Histopathologic evaluation showed similar results (P = .016) with an average necrosis of 87.5% (range, 80%-95%) for DEE transarterial chemoembolization (n = 4) versus 26% (range, 0-70%) for TAE (n = 5). Percentage of necrosis seen on microscopy correlated significantly (P = .0005) with radiologic findings, as 4 tumors in each arm were evaluated by both CT and microscopy. No major complications were observed in either group. CONCLUSIONS: DEE transarterial chemoembolization is safe for treating localized RCC and has a significantly superior cytoreductive effect compared with TAE.
Subject(s)
Carcinoma, Hepatocellular/therapy , Carcinoma, Renal Cell/therapy , Chemoembolization, Therapeutic/methods , Aged , Angiography , Biopsy , Doxorubicin/administration & dosage , Female , Humans , Male , Polyvinyl Alcohol/administration & dosage , Prospective Studies , Treatment OutcomeABSTRACT
OBJECTIVES: To develop an algorithm to segment and obtain an estimate of total intracranial volume (tICV) from computed tomography (CT) images. MATERIALS AND METHODS: Thirty-six CT examinations from 18 patients were included. Ten patients were examined twice the same day and eight patients twice six months apart (these patients also underwent MRI). The algorithm combines morphological operations, intensity thresholding and mixture modelling. The method was validated against manual delineation and its robustness assessed from repeated imaging examinations. Using automated MRI software, the comparability with MRI was investigated. Volumes were compared based on average relative volume differences and their magnitudes; agreement was shown by a Bland-Altman analysis graph. RESULTS: We observed good agreement between our algorithm and manual delineation of a trained radiologist: the Pearson's correlation coefficient was r = 0.94, tICVml[manual] = 1.05 × tICVml[automated] - 33.78 (R(2) = 0.88). Bland-Altman analysis showed a bias of 31 mL and a standard deviation of 30 mL over a range of 1265 to 1526 mL. CONCLUSIONS: tICV measurements derived from CT using our proposed algorithm have shown to be reliable and consistent compared to manual delineation. However, it appears difficult to directly compare tICV measures between CT and MRI. KEY POINTS: ⢠Automated estimation of tICV is in good agreement with manual tracing. ⢠Consistent tICV estimations from repeated measurements demonstrate the robustness of the algorithm. ⢠Automatically segmented volumes seem less variable than those from manual tracing. ⢠Unbiased and automated tlCV estimation is possible from CT.
Subject(s)
Brain/diagnostic imaging , Image Processing, Computer-Assisted/methods , Tomography, X-Ray Computed/methods , Aged , Aged, 80 and over , Algorithms , Female , Follow-Up Studies , Humans , Image Processing, Computer-Assisted/statistics & numerical data , Likelihood Functions , Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging/statistics & numerical data , Male , Middle Aged , Organ Size , Phantoms, Imaging , Reproducibility of Results , Retrospective Studies , Tomography, X-Ray Computed/statistics & numerical dataABSTRACT
BACKGROUND: In the last few years new potential applications have been developed for contrast-enhanced ultrasound (CEUS) and the management of breast diseases, but there is still some debate concerning the optimal dose to evaluate breast lesions, especially as a diagnostic tool. PURPOSE: To compare different CEUS doses of injected contrast agent in order to establish an optimal dose for the diagnosis of invasive breast cancer. MATERIAL AND METHODS: In Group A we compared the bolus dose of 1.2 mL vs. 2.4 mL and in Group B we compared the bolus dose of 2.4 mL vs. 4.8 mL (26 and 25 invasive carcinomas, respectively). CEUS was performed in real-time contrast harmonic imaging (CHI) using a L9-3 MHz probe. All examinations were recorded in a contrast side/side imaging mode loop for 120 s. Wash-in and wash-out patterns of the contrast agent were analyzed with advanced US quantification software and kinetic curves were used for statistical analysis. RESULTS: In Group B (2.4 mL vs. 4.8 mL), more and stronger correlation was found among kinetic parameters (area under the curve, P < 0.00001; lognormal model parameters, µ, P = 0.0007 and σ, P < 0.0001; mean transit time, P < 0.0001; model-based wash-out ratios, W21m, P = 0.0002; W50m, P = 0.0001; time-to-peak, P = 0.005) as compared to Group A (1.2 mL vs. 2.4 mL). CONCLUSION: The optimal way to evaluate kinetic features of invasive breast tumors using real-time CEUS is with an injection of contrast agent of either 2.4 mL or 4.8 mL.
Subject(s)
Breast Neoplasms/pathology , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Phospholipids/administration & dosage , Sulfur Hexafluoride/administration & dosage , Ultrasonography, Mammary/methods , Adult , Aged , Aged, 80 and over , Computer Systems , Contrast Media/administration & dosage , Dose-Response Relationship, Drug , Female , Humans , Middle Aged , Neoplasm Invasiveness , Reproducibility of Results , Sensitivity and SpecificitySubject(s)
Bone Neoplasms/diagnostic imaging , Multimodal Imaging/methods , Radiation Dosage , Tomography, Emission-Computed, Single-Photon/methods , Tomography, X-Ray Computed/methods , Aged , Bone Neoplasms/secondary , Bone and Bones/diagnostic imaging , Feasibility Studies , Female , Humans , MaleABSTRACT
Fibroblast activation protein is a promising target for oncologic molecular imaging with radiolabeled fibroblast activation protein inhibitors (FAPI) in a large variety of cancers. However, there are yet no published recommendations on how to set up an optimal imaging protocol for FAPI PET/CT. It is important to optimize the acquisition duration and strive toward an acquisition that is sufficiently short while simultaneously providing sufficient image quality to ensure a reliable diagnosis. The aim of this study was to evaluate the feasibility of reducing the acquisition duration of [68Ga]FAPI-46 imaging while maintaining satisfactory image quality, with certainty that the radiologist's ability to make a clinical diagnosis would not be affected. Methods: [68Ga]FAPI-46 PET/CT imaging was performed on 10 patients scheduled for surgical resection of suspected pancreatic cancer, 60 min after administration of 3.6 ± 0.2 MBq/kg. The acquisition time was 4 min/bed position, and the raw PET data were statistically truncated and reconstructed to represent images with an acquisition duration of 1, 2, and 3 min/bed position, additional to the reference images of 4 min/bed position. Four image quality criteria that focused on the ability to distinguish specific anatomic details, as well as perceived image noise and overall image quality, were scored on a 4-point Likert scale and analyzed with mixed-effects ordinal logistic regression. Results: A trend toward increasing image quality scores with increasing acquisition duration was observed for all criteria. For the overall image quality, there was no significant difference between 3 and 4 min/bed position, whereas 1 and 2 min/bed position were rated significantly (P < 0.05) lower than 4 min/bed position. For the other criteria, all images with a reduced acquisition duration were rated significantly inferior to images obtained at 4 min/bed position. Conclusion: The acquisition duration can be reduced from 4 to 3 min/bed position while maintaining satisfactory image quality. Reducing the acquisition duration to 2 min/bed position or lower is not recommended since it results in inferior-quality images so noisy that clinical interpretation is significantly disrupted.
ABSTRACT
Human epidermal growth factor receptor 2 (HER2) is a major prognostic and predictive marker overexpressed in 15-20% of breast cancers. The diagnostic reference standard for selecting patients for HER2-targeted therapy is based on the analysis of tumor biopsies. Previously patients were defined as HER2-positive or -negative; however, with the approval of novel treatment options, specifically the antibody-drug conjugate trastuzumab deruxtecan, many breast cancer patients with tumors expressing low levels of HER2 have become eligible for HER2-targeted therapy. Such patients will need to be reliably identified by suitable diagnostic methods. Biopsy-based diagnostics are invasive, and repeat biopsies are not always feasible. They cannot visualize the heterogeneity of HER2 expression, leading to a substantial number of misdiagnosed patients. An alternative and highly accurate diagnostic method is molecular imaging with radiotracers. In the case of HER2, various studies demonstrate the clinical utility and feasibility of such approaches. Radiotracers based on Affibody® molecules, small, engineered affinity proteins with a size of ~6.5 kDa, are clinically validated molecules with favorable characteristics for imaging. In this article, we summarize the HER2-targeted therapeutic landscape, describe our experience with imaging diagnostics for HER2, and review the currently available clinical data on HER2-Affibody-based molecular imaging as a novel diagnostic tool in breast cancer and beyond.
ABSTRACT
OBJECTIVES: To increase understanding of optimal imaging parameters [ 18 F]PSMA-1007 when imaging patients with prostate cancer and to determine interrater agreement using [ 18 F]PSMA-1007. METHODS: In this observational study, four independent physicians read reconstruction sets using bedtimes of 1, 2 and 3 minutes of patients undergoing [ 18 F]PSMA-1007. positron emission topography. Clear and equivocal lesions and their locations were recorded. Image noise was rated on a four-point scale. Lesion counts were compared using inter-class correlation whereas noise ratings were compared using generalized estimating equations. Repeated cases were used to assess intra-rater agreement. RESULTS: Sixty reconstruction sets of 16 consecutively examined participants were included. Participants had a mean age of 71.5 years, six of them were examined prior to any treatment, three had a history of radiotherapy and seven of prostatectomy. Median Gleason score of primary tumors was 7. Imaging was performed after a mean of 132â min using a mean 3.95 MBq/Kg body weight of [ 18 F] PSMA-1007. Neither the total number of lesions per location nor the proportion of equivocal lesions varied consistently between bedtimes. Inter-rater reliability scores varied depending on location from 0.40 to 1.0 and were similar for all bedtimes. Intra-rater reliability varied between 0.70 and 0.76 for the three different bedtimes. Noise ratings were significantly lower for 1 minute than 3 minutes per bed. CONCLUSION: In the setting of [ 18 F]PSMA-1007 PET CT, 1, 2 and 3 minutes per bed produce similar results unlikely to affect clinical interpretation. Image noise ratings favor 2 and 3 minutes per bed.
Subject(s)
Niacinamide/analogs & derivatives , Oligopeptides , Positron-Emission Tomography , Prostatic Neoplasms , Male , Humans , Aged , Reproducibility of Results , Positron Emission Tomography Computed Tomography/methods , Prostatic Neoplasms/pathology , Gallium RadioisotopesABSTRACT
Patients with HER2-low metastatic breast cancer (mBC), defined as an immunohistochemistry (IHC) score of 1+ or 2+ without HER2 gene amplification, may benefit from HER2 antibody-drug conjugates. Identifying suitable candidates is a clinical challenge because of spatial and temporal heterogeneity in HER2 expression and discrepancies in pathologic reporting. We aimed to investigate the feasibility and safety of HER2-specific PET imaging with [68Ga]Ga-ABY-025 for visualization of HER2-low mBC. Methods: A prospective pilot study was done with 10 patients who had HER2-low mBC, as part of a phase 2 basket imaging study with [68Ga]Ga-ABY-025 in HER2-expressing solid tumors. Patients were recruited at the Breast Clinic at the Karolinska University Hospital, Stockholm, Sweden. PET/CT images were acquired 3 h after injection of 200 MBq of [68Ga]Ga-ABY-025. The SUVmax was used to quantify tracer uptake. Ultrasound-guided tumor biopsies were guided by results from the HER2 PET. The main outcome-the safety and feasibility of HER2 PET in patients with HER2-low mBC, measured the occurrence of possible procedure-related adverse events. Results: Ten patients with HER2-low mBC underwent [68Ga]Ga-ABY-025 PET/CT with paired tumor biopsies. No adverse events occurred. In all patients, [68Ga]Ga-ABY-025-avid lesions with substantial intra- and interindividual heterogeneity in tracer uptake were noted. In 8 of 10 patients with ABY-025-avid lesions, the HER2-low status of the corresponding lesions was confirmed by IHC or in situ hybridization. Two patients had an IHC score of 0 in the tumor biopsies:1 in a cutaneous lesion with a low SUVmax and 1 in a liver metastasis with a high SUVmax but a "cold" core. Conclusion: The visualization of HER2-low mBC with [68Ga]Ga-ABY-025 PET/CT was feasible and safe. Areas of tracer uptake showed varying levels of HER2 expression on IHC. The observed intra- and interindividual heterogeneity in [68Ga]Ga-ABY-025 uptake suggested that HER2 PET might be used as a tool for the noninvasive assessment of disease heterogeneity and has the potential to identify patients in whom HER2-targeted drugs can have a clinical benefit.
Subject(s)
Breast Neoplasms , Peptide Fragments , Positron Emission Tomography Computed Tomography , Receptor, ErbB-2 , Staphylococcal Protein A , Humans , Pilot Projects , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/metabolism , Receptor, ErbB-2/metabolism , Female , Middle Aged , Aged , Gallium Radioisotopes , Adult , Prospective Studies , Radiopharmaceuticals , Positron-Emission TomographySubject(s)
Carcinoma, Hepatocellular , Ethiodized Oil , Antibiotics, Antineoplastic , Doxorubicin , Emulsions , Humans , Liver Neoplasms , Treatment OutcomeABSTRACT
OBJECTIVES: To correlate contrast-enhanced ultrasound (CEUS) kinetic parameters with traditional and molecular prognostic factors in invasive breast cancer. METHODS: Seventy-five invasive breast cancers were evaluated with contrast harmonic imaging after the injection of a bolus dose of 2.4 ml sulphur hexafluoride microbubble contrast agent. The lognormal function was used for quantitative analysis of kinetic data. These parameters correlated with traditional prognostic factors (tumour size, histological type, tumour grade, axillary lymph node status) and immunohistochemical biomarkers (ER, PR and HER2 status). RESULTS: Statistically significant correlation was found between time-to-peak and tumour grade (P value = 0.023), PR status (P value = 0.042) and axillary node status (P value = 0.025). Wash-out ratio, measured at 21 s was significantly associated with ER status (P value = 0.042) and PR status (P value = 0.026). CONCLUSIONS: Invasive breast carcinomas exhibiting earlier peak enhancement and faster elimination of microbubble contrast agent at CEUS are found to be associated with established predictors of poor prognosis.
Subject(s)
Adenocarcinoma, Mucinous/diagnostic imaging , Adenocarcinoma/diagnostic imaging , Breast Neoplasms/diagnostic imaging , Carcinoma, Ductal/diagnostic imaging , Carcinoma, Papillary/diagnostic imaging , Image Enhancement/methods , Sulfur Hexafluoride , Adenocarcinoma/pathology , Adenocarcinoma/secondary , Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/secondary , Adult , Aged , Aged, 80 and over , Area Under Curve , Axilla/diagnostic imaging , Biopsy , Breast Neoplasms/pathology , Carcinoma, Ductal/pathology , Carcinoma, Ductal/secondary , Carcinoma, Papillary/pathology , Carcinoma, Papillary/secondary , Contrast Media , Female , Humans , Kinetics , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Middle Aged , Models, Biological , Multivariate Analysis , Neoplasm Grading , Prognosis , Sentinel Lymph Node Biopsy , UltrasonographyABSTRACT
BACKGROUND: Sentinel node (SN) biopsy in esophageal cancer has the potential of becoming an important tool for ruling out the presence of lymph node metastases in patients opted for less extensive surgery without neoadjuvant treatment. PURPOSE: To investigate preoperative SN imaging in esophageal cancer using hybrid single photon emission computed tomography (SPECT)/CT. MATERIAL AND METHODS: Eight patients with esophageal cancer scheduled for thoracoabdominal esophagectomy after neoadjuvant treatment, underwent endoscopic submucosal injection of (99m)Tc-nanocoll the day before surgery, followed by imaging with SPECT/CT for preoperative detection. Intraoperative detection of SNs was performed with a gamma probe. RESULTS: SNs were identified by SPECT/CT in 7/8 cases (88%) and by gamma probe in all cases. The median number of identified lymph node stations with SN in the operating field was 1 (range 0-2) for SPECT/CT and 1 (range 1-3) for gamma probe. The median distance between the perceived location of the respective SN according to SPECT/CT and the location identified with the gamma probe was <5 mm (range <5-15 mm). In one patient who had a complete histologic response to neoadjuvant treatment in the primary tumor, there was one single metastasis that was not contained in one of the SNs. CONCLUSION: Preoperative identification of sentinel nodes with hybrid SPECT/CT after endoscopic injection of radiocolloid is a technique with obvious potential for SN mapping in esophageal cancer.
Subject(s)
Esophageal Neoplasms/pathology , Multimodal Imaging/methods , Sentinel Lymph Node Biopsy/methods , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed , Aged , Esophageal Neoplasms/diagnostic imaging , Esophagoscopy , Female , Humans , Lymphatic Metastasis/pathology , Male , Middle Aged , Neoplasm Staging , Radiographic Image Interpretation, Computer-Assisted , Radiopharmaceuticals , Technetium Tc 99m Aggregated AlbuminABSTRACT
Correct and timely diagnosis of pancreatic cancer (PC) is essential for treatment selection but is still clinically challenging. Standard-of-care imaging methods can sometimes not differentiate malignancies from inflammatory lesions or detect malignant transformation in premalignant lesions. This interim analysis of a prospective clinical trial aimed to evaluate the diagnostic accuracy of [68Ga]fibroblast activation protein inhibitor (FAPI)-46 PET/CT for PC and determine the sample size needed to demonstrate whether this imaging technique improves the characterization of equivocal lesions detected by standard-of-care imaging methods. Methods: [68Ga]FAPI-46 PET/CT imaging was performed on 30 patients scheduled for surgical resection of suspected PC. Target lesions were delineated, SUVmax and SUVmean were determined, and the results were compared with those of standard-of-care imaging. Receiver operating characteristics were calculated for the whole cohort and a subcohort of 11 patients with an equivocal clinical imaging work-up preoperatively. Postoperative histopathologic findings served as a reference standard, and the statistical power was determined. Results: Histopathologic examination revealed malignancy in 20 patients and benign lesions in 10 patients. Significantly elevated [68Ga]FAPI-46 uptake was observed in malignant tumors compared with benign lesions (P < 0.001). Receiver-operating-characteristic analyses established optimal cutoffs for both SUVs for differentiation of malignant from nonmalignant pancreatic tumors. The optimal SUVmax cutoff was 10.2 and showed 95% sensitivity and 80% specificity for the whole cohort, as well as 100% diagnostic accuracy when considering the subcohort with equivocal imaging work-up only. For sufficient statistical power, 38 equivocal observations are needed. Conclusion: We conclude that [68Ga]FAPI-46 PET/CT can accurately differentiate malignant from benign pancreatic lesions deemed equivocal by standard-of-care imaging. This trial will therefore continue to recruit a total of 120 patients to reach those 38 equivocal observations needed for sufficient statistical power. On the basis of our findings, we propose that [68Ga]FAPI-46 PET/CT not only can be clinically applied as a complement but also could become a necessary tool when standard-of-care imaging is inconclusive.