Positron Emission Tomography-computed Tomography Imaging Research Articles

Support Vector Machine Parameter Optimization for Positron Emission Tomography Images for Estimation of Recurrent Laryngeal Nerve Injury with Thyroid Nodules

This study aimed to explore positron emission tomography-computed tomography (PET-CT) images based on support vector machine (SVM) algorithm for the classification of thyroid nodules (TN) and its evaluation value in postoperative injury rate (PPIR) of recurrent laryngeal nerve (RLN). The parameters of the SVM algorithm were optimized using the particle swarm optimization (PSO) algorithm. A total of 58 patients who were diagnosed with TN by PET/CT at a hospital were divided into a group with benign nodules (group B, 25 cases) and a group with malignant nodules (group M, 33 cases). The characteristics of the PET-CT images and difference in the max standardized uptake value (SUVmax) of PET-CT were analyzed. The PPIR of RLN was calculated. It was found that when the number of iterations was 19, the fitness and the classification accuracy of the SVM algorithm was 98.3% and 91.1%, respectively. When SUVmax = 4.56, its sensitivity and specificity were 81.33% and 76.18%, respectively. The SUVmax of group B was much lower ( P < 0.01 ). It indicated that the established method could realize higher classification accuracy on TN and was of great significance in the evaluation of the PPIR of RLN.

Establishment of typical adult CT dose indicators for PET-CT scans in Slovenia

The aim was to determine typical values of diagnostic reference level (DRL) quantities for the computed tomography (CT) part of the most common positron emission tomography—computed tomography (PET-CT) procedures in Slovenia. The most common PET-CT procedures were identified, and data collated for 565 patients imaged in all three PET-CT units in Slovenia during a time span of 11 months. As the number of facilities is too low to establish national DRLs, we followed ICRP recommendations and determined typical values of DRL quantities as the median values of the pooled set of data. Mean, median, and standard deviation of CT dose index (CTDIvol) and total dose length product (DLP) for the CT part of the most common PET-CT procedures were determined for pooled data as well as for each PET-CT unit. The data were compared between all three units to identify possible outliers that would likely benefit from optimization. Three most common CT protocols covering approximately 2/3 of all PET-CT imaging performed in Slovenia were considered: from the base of the cranium to the middle of the femur, from the top of the head to the middle of the femur, and for the whole-body PET-CT. The established typical values in terms of total DLP were 295, 359, and 676 mGyċcm, respectively; and in terms of CTDIvol 3.05, 3.22, and 3.60 mGy, respectively. Comparing the data between all three units showed significantly higher (p < 0.001) patient doses on one unit, indicating a need for optimization. The results present the first-time data on the national typical values of DRL quantities for the CT part of most common PET-CT procedures in Slovenia. While the determined typical values are within the DRL values established in some other countries, significant differences were found between the individual units included in the study.

Value of (18)F-FDG PET-CT imaging to predict epidermal growth factor receptor mutations in patients with lung squamous cell carcinoma

Objective: To investigate the value of (18)F-fluorodeoxy glucose ((18)F-FDG) positron emission tomography/computed tomography (PET-CT) in predicting the epidermal growth factor receptor (EGFR) mutations in patients with lung squamous cell carcinoma. Methods: We retrospectively analyzed the clinical data and (18)F-FDG PET-CT imaging data of 206 patients with lung squamous cell carcinoma confirmed by pathology and underwent EGFR mutation test in the First Affiliated Hospital of Nanjing Medical University from June 2013 to October 2018. Receiver operating characteristic (ROC) curve analysis was performed to quantify the predictive value of maximum standard uptake value (SUV(max)), metabolic tumor volume (MTV), total lesion glycolysis (TLG). The Chi-squared test was used to assess the difference in PET parameters. A multivariate Logistic regression analysis was performed to yield the parameters with statistic difference. Results: All of 206 patients with lung squamous cell carcinoma showed a high (18)F-FDG uptake. The median of SUV(max), MTV and TLG were 19.14, 37.69 cm(3) and 291.73, respectively. Among the 206 patients, EGFR mutations were identified in 14 cases, including 7 with exon 21 (L858R) mutation, 6 with exon 19 mutation and 1 with exon 20 mutation. ROC curve showed that the AUC of SUV(max), MTV and TLG were 0.624 (95% CI=0.454-0.794, P=0.122), 0.892 (95% CI=0.811-0.973, P<0.001) and 0.860 (95% CI=0.768-0.952, P<0.001), respectively. The median SUV(max) (19.14) was used as the cutoff points due to the small value of AUC. The cutoff point of MTV was 20.09 cm(3), the cutoff point of TLG was 211.07. Univariate analysis showed that the sex, smoking history, M stage, MTV and TLG were associated with EGFR mutations (all P<0.05). Logistic multivariate analysis showed that the sex, smoking history and TLG were the independent predictors of EGFR mutation (all P<0.05). Conclusion: TLG detected by (18)F-FDG PET/CT is an independent factor for predicting EGFR mutation in patients with lung squamous cell carcinoma, and has certain reference value for predicting EGFR mutation.

18F-fluorodeoxyglucose positron emission tomography-computed tomography imaging of leiomyomatosis peritonealis disseminata.

Leiomyomatosis peritonealis disseminata (LPD) is a rare benign condition characterized by multiple smooth muscle implants in the peritoneal cavity. The clinical presentation is usually nonspecific abdominal discomfort and nontender abdominal mass. Preoperative imaging usually points to suggests malignancy due to its unusual location, but the diagnosis can only be confirmed by histopathological examination. We share 18F-Fluorodeoxyglucose positron emission tomography-computed tomography images of a 43-year-old woman diagnosed with LPD and briefly discuss the clinical aspects of this disease.

Development and validation of tumor-to-blood based nomograms for preoperative prediction of lymph node metastasis in lung cancer.

BackgroundTo develop and validate tumor‐to‐blood based nomograms for preoperative prediction of lymph node (LN) metastasis in patients with lung cancer (LC).MethodsA prediction model was developed in a primary cohort comprising 330 LN stations from patients with pathologically confirmed LC, these data having been gathered from January 2016 to June 2019. Tumor‐to‐blood variables of LNs were calculated from positron emission tomography‐computed tomography (PET‐CT) images of LC and the short axis diameters of LNs were measured on CT images. Tumor‐to‐blood variables, number of stations suspected of harboring LN metastasis according to PET, and independent clinicopathological risk factors were included in the final nomograms. After being internally validated, the nomograms were used to assess an independent validation cohort containing 101 consecutive LN stations accumulated from July 2019 to March 2020.ResultsFour tumor‐to‐blood variables (left atrium, inferior vena cava, liver, and aortic arch) and the maximum standardized uptake value (SUVmax) for LNs were found to be significantly associated with LN status (p < 0.001 for both primary and validation cohorts). Five predictive nomograms were built. Of these, one with LN SUVmax/left atrium SUVmax was found to be optimal for predicting LN status with AUC 0.830 (95% confidence interval [CI]: 0.774–0.886) in the primary cohort and AUC 0.865 (95% CI: 0.782–0.948) in the validation cohort. All models showed good discrimination, with a modest C‐index, and good calibration in both primary and validation cohorts.ConclusionsWe have developed tumor‐to‐blood based nomograms that incorporate identified clinicopathological risk factors and facilitate preoperative prediction of LN metastasis in LC patients.

Aanhoudende koorts zonder focus met lymfadenopathieën: infectie, inflammatie of maligniteit?

Persistent fever without focus but with lymphadenopathy: infection, inflammation or malignancy? Adult-onset Still’s disease (AOSD) is a rare auto-inflammatory disease in which four cardinal signs have been described: rash, spiking fever, arthritis or arthralgia and hyperleucocytosis with neutrophilia. Nevertheless, diagnosis can be challenging as infectious, other inflammatory or neoplastic diseases need to be ruled out. It affects typically young adults (from 16 to 35 years). The disease can be controlled with non-steroidal anti-inflammatory agents and glucocorticoids. To date, treatments as Il-6, IL-1 or anti-TNFα can be used in glucocorticoid-dependent or refractory patients. We present a case of a 22-year old woman with all four cardinal symptoms in which all cultures and infectious serology resulted negative. Also, auto-immune markers were negative. Because of diffuse bilateral supra- and infradiaphragmatic enlarged lymph nodes up to 1.6 cm in size on computed tomography (CT), additional positron emission tomography-computed tomography imaging (PET-CT-scan) was performed. Besides the multiple enlarged lymph nodes, increased tracer capture was shown in the spleen and bone marrow. All of this was suspicious for high-grade lymphoma. Eventually, an additional bone marrow biopsy with aspiration and lymph node biopsy could rule out a lymphoproliferative process and the diagnosis of AOSD could be made. This case report highlights the importance of a profound diagnostic work-up in fever of unknown origin.

A case of Takayasu’s arteritis presented with fever of unknown origin: Diagnostic value of 18f-FDG PET/CT imaging

Takayasu’s arteritis is a chronic vasculitis of the large vessels and has a rare initial presentation of fever of unknown origin (FUO), renders the condition difficult to diagnose. Fluorodeoxyglucose (FDG) positron-emission tomography-computed tomography (PET-CT) can assist in the early diagnosis of Takayasu’s Arteritis patients with FUO and can improve the prognosis of such patients. In this case report, we describe a 27-year- old female presented with one-month history of FUO, showing heterogeneous increased FDG accumulation along the walls of ascending and arch of aorta, left subclavian artery and right brachiocephalic truncus at PET-CT imaging.

Elective neck dissection versus positron emission tomography-computed tomography-guided management of the neck in clinically node-negative early oral cavity cancer: A cost-utility analysis.

In early oral cavity cancer, elective neck dissection (END) for the clinically node-negative (cN0) neck improves survival compared with observation. This paradigm has been challenged recently by the use of positron emission tomography-computed tomography (PET-CT) imaging in the cN0 neck. To inform this debate, we performed an economic evaluation comparing PET-CT-guided therapy with routine END in the cN0 neck. Patients with T1-2N0 lateralized oral tongue cancer were analyzed. A Markov model over a 40-year time horizon simulated treatment, disease recurrence, and survival from a US health care payer perspective. Model parameters were derived from a review of the literature. The END strategy was dominant, with a cost savings of $1576.30 USD, an increase of 0.055 quality-adjusted life years (QALYs), a net monetary benefit of $4303 USD, and a 0.22 life-year advantage. END was sensitive to variation in cost and utilities in deterministic and probabilistic sensitivity analyses. PET-CT became the preferred strategy when decreasing occult nodal disease to 18% and increasing the negative predictive value (NPV) of PET-CT to 89% in 1-way sensitivity analyses. In probabilistic sensitivity analysis, assuming a cost effectiveness threshold of $50,000 USD/QALY, END was dominant in 64% of simulations and cost effective in 69.8%. END is a cost-effective strategy compared with PET-CT in patients who have node-negative oral cancer. Although lower PET standardized uptake value thresholds would result in fewer false negatives and improved NPV, it is still uncertain that PET-CT would be cost effective, as this would likely result in more false positive tests.

Sodium Fluoride-18 and Radium-223 Dichloride Uptake Colocalize in Osteoblastic Mouse Xenograft Tumors.

Background: Patients with osteoblastic bone metastases are candidates for radium-223 (223RaCl2) therapy and may undergo sodium fluoride-18 (18F-NaF) positron emission tomography-computed tomography imaging to identify bone lesions. 18F-NaF has been shown to predict 223RaCl2 uptake, but intratumor distributions of these two agents remain unclear. In this study, the authors evaluate the spatial distribution and relative uptakes of 18F-NaF and 223RaCl2 in Hu09-H3 human osteosarcoma mouse xenograft tumors at macroscopic and microscopic levels to better quantify their correlation. Materials and Methods: 18F-NaF and 223RaCl2 were co-injected into Hu09-H3 xenograft tumor severe combined immunodeficient mice. Tumor content was determined from in vivo biodistributions and visualized by PET, single photon emission computed tomography, and CT imaging. Intratumor distributions were visualized by quantitative autoradiography of tumor tissue sections and compared to histology of the same or adjacent sections. Results: 18F and 223Ra accumulated in proportional amounts in whole Hu09-H3 tumors (r2 = 0.82) and in microcalcified regions within these tumors (r2 = 0.87). Intratumor distributions of 18F and 223Ra were spatially congruent in these microcalcified regions. Conclusions: 18F-NaF and 223RaCl2 uptake are strongly correlated in heterogeneously distributed microcalcified regions of Hu09-H3 xenograft tumors, and thus, tumor accumulation of 18F is predictive of 223Ra accumulation. Hu09-H3 xenograft tumors appear to possess certain histopathological features found in patients with metastatic bone disease and may be useful in clarifying the relationship between administered 223Ra dose and therapeutic effect.

Clinical TNM staging for esophageal, gastric, and colorectal cancers in the era of neoadjuvant therapy: A systematic review of the literature.

AimClinical staging is vital for selecting appropriate candidates and designing neoadjuvant treatment strategies for advanced tumors. The aim of this review was to evaluate diagnostic abilities of clinical TNM staging for gastrointestinal, gastrointestinal cancers.MethodsWe conducted a systematic review of recent publications to evaluate the accuracy of diagnostic modalities on gastrointestinal cancers. A systematic literature search was performed in PubMed/MEDLINE using the keywords “TNM staging,” “T4 staging,” “distant metastases,” “esophageal cancer,” “gastric cancer,” and “colorectal cancer,” and the search terms used in Cochrane Reviews between January 2005 to July 2020. Articles focusing on preoperative diagnosis of: (a) depth of invasion; (b) lymph node metastases; and (c) distant metastases were selected.ResultsAfter a full‐text search, a final set of 55 studies (17 esophageal cancer studies, 26 gastric cancer studies, and 12 colorectal cancer studies) were used to evaluate the accuracy of clinical TNM staging. Positron emission tomography–computed tomography (PET‐CT) and/or magnetic resonance imaging (MRI) were the best modalities to assess distant metastases. Fat and fiber mode of CT may be useful for T4 staging of esophageal cancer, CT was a partially reliable modality for lymph node staging in gastric cancer, and CT combined with MRI was the most reliable modality for liver metastases from colorectal cancer.ConclusionThe most reliable diagnostic modality differed among gastrointestinal cancers depending on the type of cancer. Therefore, we propose diagnostic algorithms for clinical staging for each type of cancer.

In vivo evaluation of percutaneous carbon dioxide treatment for improving intratumoral hypoxia using 18F-fluoromisonidazole PET-CT.

Carbon dioxide (CO2) treatment is reported to have an antitumor effect owing to the improvement in intratumoral hypoxia. Previous studies were based on histological analysis alone. In the present study, the improvement in intratumoral hypoxia by percutaneous CO2 treatment in vivo was determined using 18F-fluoromisonidazole positron emission tomography-computed tomography (18F-FMISO PET-CT) images. Twelve Japanese nude mice underwent implantation of LM8 tumor cells in the dorsal subcutaneous area 2 weeks before percutaneous CO2 treatment and 18F-FMISO PET-CT scans. Immediately after intravenous injection of 18F-FMISO, CO2 and room air were administered transcutaneously in the CO2-treated group (n=6) and a control group (n=6), respectively; each treatment was performed for 10 minutes. PET-CT was performed 2 h after administration of 18F-FMISO. 18F-FMISO tumor uptake was quantitatively evaluated using the maximum standardized uptake value (SUVmax), tumor-to-liver ratio (TLR), tumor-to-muscle ratio (TMR), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Mean ± standard error of the mean (SEM) of the tumor volume was not significantly different between the two groups (CO2-treated group, 1.178±0.450 cm3; control group, 1.368±0.295 cm3; P=0.485). Mean ± SEM of SUVmax, TLR, MTV (cm3) and TLG were significantly lower in the CO2-treated group compared with the control group (0.880±0.095 vs. 1.253±0.071, P=0.015; 1.063±0.147361 vs. 1.455±0.078, P=0.041; 0.353±0.139 vs. 1.569±0.438, P=0.015; 0.182±0.070 vs. 1.028±0.338, P=0.015), respectively. TMR was not significantly different between the two groups (4.520±0.503 vs. 5.504±0.310; P=0.240). In conclusion, 18F-FMISO PET revealed that percutaneous CO2 treatment improved intratumoral hypoxia in vivo. This technique enables assessment of the therapeutic effect in CO2 treatment by imaging, and may contribute to its clinical application.

Skeletal muscle metabolism on whole-body positron emission tomography during pitching

BackgroundElectromyography (EMG) has been used for evaluating skeletal muscle activity during pitching. However, it is difficult to observe the influence of movement on skeletal muscle activity in deep-lying regions of the trunk and extremities using EMG. An alternative method that may be used is the measurement of glucose metabolism of skeletal muscle using positron emission tomography-computed tomography (PET-CT). This technique is a reliable measure of muscle metabolism, demonstrating a high correlation with the intensity of muscle activity. This study aimed to evaluate whole-body skeletal muscle metabolism during pitching using PET-CT.MethodsTen uninjured, skilled, adult pitchers, who were active at college or professional level, threw 40 baseballs at maximal effort before an intravenous injection of 37 MBq of 18F-fluorodeoxyglucose (FDG). Subsequently, additional 40 balls were pitched. PET-CT images were obtained 50 min after FDG injection, and regions of interest were defined within 72 muscles. The standardized uptake value (SUV) of FDG by muscle tissue per unit volume was calculated, and the mean SUV of the pitchers was compared with that of a healthy adult control group who did not exercise before the measurements. Statistical analysis was performed using a t-test, and P < 0.05 was considered statistically significant.ResultsWhole-body PET images showed a significant increase in glucose metabolism in the muscle groups of the fingers and toes in both the throwing and non-throwing sides. Additionally, asymmetric increases in glucose metabolism were observed in the muscles of the thigh.ConclusionsThis is the first study to evaluate whole-body muscle metabolism during pitching using PET-CT. Our findings would be useful in determining the training required for pitchers, and can be further applied to other sporting activities that involve throwing.

Serial Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Scan Distinguishing Infected Seroma from Recurrence in a Necrotic Lymph Node in a Case of Squamous Cell Carcinoma of the Right Kidney.

Seroma can occur as a complication following nephroureterectomy. We report a case of squamous cell carcinoma of the kidney, postnephroureterectomy where serial fluorodeoxyglucose positron emission tomography-computed tomography images helped in distinguishing the diagnostic dilemma between lymph node recurrence and infected seroma.

PET-enabled dual-energy CT: image reconstruction and a proof-of-concept computer simulation study

Standard dual-energy computed tomography (CT) uses two different x-ray energies to obtain energy-dependent tissue attenuation information to allow quantitative material decomposition. The combined use of dual-energy CT and positron emission tomography (PET) may provide a more comprehensive characterization of disease states in cancer and other diseases. However, the integration of dual-energy CT with PET is not trivial, either requiring costly hardware upgrades or increasing radiation exposure. This paper proposes a different dual-energy CT imaging method that is enabled by PET. Instead of using a second x-ray CT scan with a different energy, this method exploits time-of-flight PET image reconstruction via the maximum likelihood attenuation and activity (MLAA) algorithm to obtain a 511 keV gamma-ray attenuation image from PET emission data. The high-energy gamma-ray attenuation image is then combined with the low-energy x-ray CT of PET/CT to provide a pair of dual-energy CT images. A major challenge with the standard MLAA reconstruction is the high noise present in the reconstructed 511 keV attenuation map, which would not compromise the PET activity reconstruction too much but may significantly affect the performance of the gamma-ray attenuation image for material decomposition. To overcome the problem, we further propose a kernel MLAA algorithm to exploit the prior information from the available x-ray CT image. We conducted a computer simulation to test the concept and algorithm for the task of material decomposition. The simulation results demonstrate that this PET-enabled dual-energy CT method is promising for quantitative material decomposition. The proposed method can be readily implemented on time-of-flight PET/CT scanners to enable simultaneous PET and dual-energy CT imaging.

Obtaining PET/CT images from non-attenuation corrected PET images in a single PET system using Wasserstein generative adversarial networks

Positron emission tomography (PET) imaging plays an indispensable role in early disease detection and postoperative patient staging diagnosis. However, PET imaging requires not only additional computed tomography (CT) imaging to provide detailed anatomical information but also attenuation correction (AC) maps calculated from CT images for precise PET quantification, which inevitably demands that patients undergo additional doses of ionizing radiation. To reduce the radiation dose and simultaneously obtain high-quality PET/CT images, in this work, we present an alternative based on deep learning that can estimate synthetic attenuation corrected PET (sAC PET) and synthetic CT (sCT) images from non-attenuation corrected PET (NAC PET) scans for whole-body PET/CT imaging. Our model consists of two stages: the first stage removes noise and artefacts in the NAC PET images to generate sAC PET images, and the second stage synthesizes CT images from the sAC PET images obtained in the first stage. Both stages employ the same deep Wasserstein generative adversarial network and identical loss functions, which encourage the proposed model to generate more realistic and satisfying output images. To evaluate the performance of the proposed algorithm, we conducted a comprehensive study on a total of 45 sets of paired PET/CT images of clinical patients. The final experimental results demonstrated that both the generated sAC PET and sCT images showed great similarity to true AC PET and true CT images based on both qualitative and quantitative analyses. These results also indicate that in the future, our proposed algorithm has tremendous potential for reducing the need for additional anatomic imaging in hybrid PET/CT systems or the need for lengthy MR sequence acquisition in hybrid PET/MRI systems.

18F-FHBG PET-CT Reporter Gene Imaging of Adoptive CIK Cell Transfer Immunotherapy for Breast Cancer in a Mouse Model.

BackgroundTo further improve the efficiency of adoptively transferred cytokine-induced killer (CIK) cell immunotherapy in breast cancer (BC), a reliable imaging method is required to visualize and monitor these transferred cells in vivo.MethodsHerpes simplex virus 1-thymidine kinase (HSV1-TK) and 9-(4-[18F]fluoro-3-(hydroxymethyl)butyl)guanine (18F-FHBG) were used as a pair of reporter gene/reporter probe for positron emission tomography (PET) imaging in this study. Following the establishment of subcutaneous BC xenograft-bearing nude mice models, induced human CIK cells expressing reporter gene HSV1-TK through lentiviral transduction were intravenously injected to nude mice. γ-radioimmunoassay was used to determine the specific uptake of 18F-FHBG by these genetically engineered CIK cells expressing HSV1-TK in vitro, and 18F-FHBG micro positron emission tomography-computed tomography (PET-CT) imaging was performed to visualize these adoptively transferred CIK cells in tumor-bearing nude mice.ResultsSpecific uptake of 18F-FHBG by CIK cells expressing HSV1-TK was clearly observed in vitro. Consistently, the localization of adoptively transferred CIK cells in tumor target could be effectively visualized by 18F-FHBG micro PET-CT reporter gene imaging.ConclusionPET-CT reporter gene imaging using 18F-FHBG as a reporter probe enables the visualization and monitoring of adoptively transferred CIK cells in vivo.

'CARMEN': is less, more? Lessons from trials in human immunodeficiency virus-Burkitt lymphoma (HIV-BL).

'CARMEN': is less, more? Lessons from trials in human immunodeficiency virus-Burkitt lymphoma (HIV-BL).

Regional Lymph Node Involvement Among Patients With De Novo Metastatic Breast Cancer

Regional nodal irradiation (RNI) for node-positive breast cancer reduces distant metastases and improves survival, albeit with limited reduction in regional nodal recurrences. The mechanism by which RNI robustly reduces distant metastases while modestly influencing nodal recurrences (ie, the presumed target of RNI) remains unclear. To determine whether some distant metastases putatively arise from occult regional nodal disease and whether regional recurrences otherwise remain largely undetected until an advanced cancer presentation. This cohort study examined patients presenting with de novo stage IV breast cancer to the Memorial Sloan Kettering Cancer Center in New York, New York, from 2006 to 2018. Medical records were reviewed to ascertain clinicopathological parameters, including estrogen receptor status and survival. Pretreatment positron emission tomography-computed tomography (PET-CT) imaging was reviewed to ascertain the extent of regional nodal involvement at metastatic diagnosis using standard nodal assessment criteria. A subset underwent regional lymph node biopsy for diagnostic confirmation and served to validate the radiographic nodal assessment. Data analysis was performed from October 2019 to February 2020. Untreated metastatic breast cancer. The primary outcome was the likelihood of regional nodal involvement at the time of metastatic breast cancer presentation and was determined by reviewing pretreatment PET-CT imaging and lymph node biopsy findings. Among 597 women (median [interquartile range] age, 53 [44-65] years) with untreated metastatic breast cancer, 512 (85.8%) exhibited regional lymph node involvement by PET-CT or nodal biopsy, 509 (85%) had involvement of axillary level I, 328 (55%) had involvement in axillary level II, 136 (23%) had involvement in axillary level III, 101 (17%) had involvement in the supraclavicular fossa, and 96 (16%) had involvement in the internal mammary chain. Lymph node involvement was more prevalent among estrogen receptor-negative tumors (92.4%) than estrogen receptor-positive tumors (83.6%). Nodal involvement at the time of metastatic diagnosis was not associated with overall survival. These findings suggest that a majority of patients with de novo metastatic breast cancer harbor regional lymph node disease at presentation, consistent with the hypothesis that regional involvement may precede metastatic dissemination. This is in alignment with the findings of landmark trials suggesting that RNI reduces distant recurrences. It is possible that this distant effect of RNI may act via eradication of occult regional disease prior to systemic seeding. The challenges inherent in detecting isolated nodal disease (which is typically asymptomatic) may account for the more modest observed benefit of RNI on regional recurrences. Alternative explanations of nodal involvement that arises concurrently or after metastatic dissemination remain possible, but do not otherwise explain the association of RNI with distant recurrence.

Enhanced immune reaction resulting from co-vaccination of WT1 helper peptide assessed on PET-CT.

It has become evident that positron emission tomography/computed tomography (PET-CT) using 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) (FDG PET-CT) can detect anti-tumor immune response induced by various immunotherapies. To evaluate whether FDG PET-CT could detect anti-cancer immune response caused by cancer vaccine therapy, we performed a retrospective analysis of FDG PET-CT imaging of patients who were treated with Wilms Tumor 1 (WT1) vaccine therapy in Osaka University during July 2008 and June 2018. Increased FDG uptakes were detected in WT1-vaccinated skin and their draining lymph nodes during the repeated vaccination. While the FDG uptakes seemed to decrease with time after the cessation of WT1 peptide vaccinations, persistence of FDG uptakes for years in WT1-vaccinated skin were also observed in 2 cases who showed good clinical course. Moreover, the FDG uptakes of patients treated with the combination vaccine of WT1 specific cytotoxic T cell (CTL) and helper peptides were significantly stronger than of those treated with the WT1 CTL peptide alone. Since it is evident that the combination vaccine can induce a more robust anti-tumor immunity than can CTL peptide vaccine alone, the FDG uptakes in WT1-vaccinated skin might reflect the degree of immune response. These results suggest that PET-CT might be a good tool for prediction of anti-tumor immune response induced by WT1 vaccine therapy. Larger scale prospective studies therefore seem to be warranted.

68 Ga-DOTATATE Positron Emission Tomography-Computed Tomography Quantification Predicts Response to Somatostatin Analog Therapy in Gastroenteropancreatic Neuroendocrine Tumors.

Somatostatin analogs (SSAs) are the frontline antitumor therapy in advanced well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A subset of patients demonstrate early disease progression on SSA therapy, yet the currently known predictors for treatment failure lack specificity to affect therapeutic decision. SSAs target tumor somatostatin receptors, the level of which can be quantitatively assessed with 68 Ga-DOTATATE positron emission tomography-computed tomography (PET/CT). We investigated the ability of 68 Ga-DOTATATE PET/CT to predict response to SSA therapy. The records of 108 consecutive patients with well-differentiated grade 1-2 GEP-NETs on SSA monotherapy who received 68 Ga-DOTATATE PET/CT scans were retrospectively reviewed to obtain baseline characteristics, 68 Ga-DOTATATE maximum standardized uptake value (SUVmax), and progression-free survival (PFS) data. The optimal SUVmax cutoff for patient stratification was obtained with receiver operating characteristic curve analysis. PFS in the high versus low SUVmax groups was compared with Kaplan-Meier survival analysis. The effects of baseline characteristics and SUVmax on PFS were examined with univariate and multivariate Cox regression. 68 Ga-DOTATATE SUVmax predicted therapeutic failure with sensitivity and specificity of 39% and 98%, respectively. SUVmax of <18.35 was associated with shorter PFS, which was reproduced in the subgroup analysis of SSA-naïve patients. Low SUVmax was the only predictor of early treatment failure (hazard ratio, 6.85) in multivariate analysis, as well as in the subgroup analysis of grade 2 GEP-NETs. Low SUVmax on 68 Ga-DOTATATE PET/CT independently predicts early failure on SSA monotherapy in patients with well-differentiated grade 1-2 GEP-NET. Patients with lack of expected benefit from SSA therapy can be readily identified using routine 68 Ga-DOTATATE PET/CT with very high specificity. Based on 68 Ga-DOTATATE positron emission tomography-computed tomography imaging, clinicians can better inform patients on the expected benefit of somatostatin analog therapy for gastroenteropancreatic neuroendocrine tumors, especially when access to the therapy is difficult, and offer proactive discussion on alternative management options.