Exploiting bacteria for cancer immunotherapy.

Immunotherapy has revolutionized the treatment of cancer but continues to be constrained by limited response rates, acquired resistance, toxicities and high costs, which necessitates the development of new, innovative strategies. The discovery of a connection between the human microbiota and cancer dates back 4,000 years, when local infection was observed to result in tumour eradication in some individuals. However, the true oncological relevance of the intratumoural microbiota was not recognized until the turn of the twentieth century. The intratumoural microbiota can have pivotal roles in both the pathogenesis and treatment of cancer. In particular, intratumoural bacteria can either promote or inhibit cancer growth via remodelling of the tumour microenvironment. Over the past two decades, remarkable progress has been made preclinically in engineering bacteria as agents for cancer immunotherapy; some of these bacterial products have successfully reached the clinical stages of development. In this Review, we discuss the characteristics of intratumoural bacteria and their intricate interactions with the tumour microenvironment. We also describe the many strategies used to engineer bacteria for use in the treatment of cancer, summarizing contemporary data from completed and ongoing clinical trials. The work described herein highlights the potential of bacteria to transform the landscape of cancer therapy, bridging ancient wisdom with modern scientific innovation.

Tumor Pre-Targeting System Using Streptavidin-Expressing Bacteria.

PURPOSE: A major obstacle to targeted cancer therapy is identifying suitable targets that are specifically and abundantly expressed by solid tumors. Certain bacterial strains selectively colonize solid tumors and can deliver genetically encoded cargo molecules to the tumor cells. Here, we engineered bacteria to express monomeric streptavidin (mSA) in tumors, and developed a novel tumor pre-targeting system by visualizing the presence of tumor-associated mSA using a biotinylated imaging probe. PROCEDURES: We constructed a plasmid expressing mSA fused to maltose-binding protein and optimized the ribosome binding site sequence to increase solubility and expression levels. E. coli MG1655 was transformed with the recombinant plasmid, expression of which is driven by the pBAD promotor. Expression of mSA was induced by L-arabinose 4 days after injection of bacteria into mice bearing CT26 mouse colon carcinoma cells. Selective accumulation of mSA in tumor tissues was visualized by optical imaging after administration of a biotinylated fluorescent dye. Counting of viable bacterial cells was also performed. RESULTS: Compared with a conventional system, the novel expression system resulted in significantly higher expression of mSA and sustained binding to biotin. Imaging signals in tumor tissues were significantly stronger in the mSA-expressing group than in non-expressing group (P = 0.0005). Furthermore, the fluorescent signal in tumor tissues became detectable again after multiple inductions with L-arabinose. The bacterial counts in tumor tissues showed no significant differences between conditions with and without L-arabinose (P = 0.45). Western blot analysis of tumor tissues confirmed expression and binding of mSA to biotin. CONCLUSIONS: We successfully engineered tumor-targeting bacteria carrying a recombinant plasmid expressing mSA, which was targeted to, and expressed in, tumor tissues. These data demonstrate the potential of this novel tumor pre-targeting system when combined with biotinylated imaging probes or therapeutic agents.

Endoscopic Hyperspectral Imaging System to Discriminate Tissue Characteristics in Tissue Phantom and Orthotopic Mouse Pancreatic Tumor Model.

In this study, we developed an endoscopic hyperspectral imaging (eHSI) system and evaluated its performance in analyzing tissues within tissue phantoms and orthotopic mouse pancreatic tumor models. Our custom-built eHSI system incorporated a liquid crystal tunable filter. To assess its tissue discrimination capabilities, we acquired images of tissue phantoms, distinguishing between fat and muscle regions. The system underwent supervised training using labeled samples, and this classification model was then applied to other tissue phantom images for evaluation. In the tissue phantom experiment, the eHSI effectively differentiated muscle from fat and background tissues. The precision scores regarding fat tissue classification were 98.3% for the support vector machine, 97.7% for the neural network, and 96.0% with a light gradient-boosting machine algorithm, respectively. Furthermore, we applied the eHSI system to identify tumors within an orthotopic mouse pancreatic tumor model. The F-score of each pancreatic tumor-bearing model reached 73.1% for the KPC tumor model and 63.1% for the Pan02 tumor models. The refined imaging conditions and optimization of the fine-tuning of classification algorithms enhance the versatility and diagnostic efficacy of eHSI in biomedical applications.

Prognostic Significance Of Sequential 18f-fdg Pet/Ct During Frontline Treatment Of Peripheral T Cell Lymphomas.

BACKGROUND/AIMS: The prognostic significance of 18F-fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography (PET/CT) in peripheral T-cell lymphomas (PTCLs) are controversial. We explored the prognostic impact of sequential 18F-FDG PET/CT during frontline chemotherapy of patients with PTCLs. METHODS: In total, 143 patients with newly diagnosed PTCLs were included. Sequential 18F-FDG PET/CTs were performed at the time of diagnosis, during chemotherapy, and at the end of chemotherapy. The baseline total metabolic tumor volume (TMTV) was calculated using the the standard uptake value with a threshold method of 2.5. RESULTS: A baseline TMTV of 457.0 cm3 was used to categorize patients into high and low TMTV groups. Patients with a requirehigh TMTV had shorter progression-free survival (PFS) and overall survival (OS) than those with a low TMTV (PFS, 9.8 vs. 26.5 mo, p = 0.043; OS, 18.9 vs. 71.2 mo, p = 0.004). The interim 18F-FDG PET/CT response score was recorded as 1, 2-3, and 4-5 according to the Deauville criteria. The PFS and OS showed significant differences according to the interim 18F-FDG PET/CT response score (PFS, 120.7 vs. 34.1 vs. 5.1 mo, p < 0.001; OS, not reached vs. 61.1 mo vs. 12.1 mo, p < 0.001). CONCLUSION: The interim PET/CT response based on visual assessment predicts disease progression and survival outcome in PTCLs. A high baseline TMTV is associated with a poor response to anthracycline-based chemotherapy in PTCLs. However, TMTV was not an independent predictor for PFS in the multivariate analysis.

Synthesis and evaluation of 18F-labeled procainamide as a PET imaging agent for malignant melanoma.

Malignant melanoma has an aggressive nature and a high metastatic propensity resulting in the highest mortality rate of any skin cancer. In this study, we synthesized 18F-labeled procainamide (PCA) for detection of melanoma using positron emission tomography (PET), and evaluated its biological characteristics. The non-decay-corrected radiochemical yield of 18F-PCA was 10-15% and its in vitro stability was over 98% for 2 h. At 1 h, cellular uptake of 18F-PCA was 3.8-fold higher in a group with the presence of l-tyrosine than in a non-l-tyrosine-treated group. Furthermore, 18F-PCA permitted visualization of B16F10 (mouse melanoma) xenografts on microPET after intravenous injection, and was retained in the tumor for 60 min, with a high tumor-to-liver uptake ratio. 18F-PCA showed specific melanoma uptake in primary lesions with a high melanin targeting ability in small animal models. 18F-PCA may have potential as a PET imaging agent for direct melanoma detection.

Prostate-specific membrane antigen expression predicts recurrence of papillary thyroid carcinoma after total thyroidectomy.

BACKGROUND: Prostate-specific membrane antigen (PSMA) overexpression has been observed in the endothelial neovasculature of several solid malignancies. This study aimed to identify PSMA expression in the primary tumor of classical papillary thyroid carcinoma (PTC) and assess the correlation between the degree of PSMA expression and recurrence. METHODS: We reviewed the electronic medical records of patients who underwent total thyroidectomy and central neck dissection, with or without lateral neck dissection, for classical PTC between 2009 and 2014 at our institution. Recurrence was defined as a structural disease based on histological confirmation on follow-up. Fifty-one patients with the recurrent structural disease were matched, using a propensity score matching method, to patients with no disease evidence during follow-up. Clinicopathological and follow-up data were collected for 102 patients. The monoclonal mouse anti-human PSMA/FOLH1/NAALADase I antibody was used for staining the primary tumor. The score of PSMA expression was classified as negative (< 5% positivity), weak (5-10 % positivity), moderate (11-49% positivity), and strong (more than 50% positivity). Clinicopathological factors were compared between patients with low and high PSMA expression. Moreover, whether the degree of PSMA expression and clinicopathological factors could predict recurrence was investigated. Cox proportional hazard regression models were used to evaluate the risk of recurrence. RESULTS: There was no significant difference in clinicopathological factors between low (negative or weak) and high (moderate or strong) PSMA expression. Gross extrathyroidal extension (ETE), absence of chronic lymphocytic thyroiditis, and high PSMA expression were all associated with lower recurrence-free survival (RFS) rate in a univariate analysis. In multivariate analysis, gross ETE (hazard ratio [HR], 2.279; 95% confidence interval [CI], 1.257-4.132; p = 0.007) and high PSMA expression (HR, 1.895; 95% CI, 1.073-3.348; p = 0.028) were associated with poor RFS. CONCLUSIONS: High PSMA expression in the primary tumor was a significant factor in predicting recurrence in classic PTC. PSMA could be a potential biomarker for personalized management for PTC.

Thyroglobulin-Based Risk Factor Repositioning for Determining Radioactive Iodine Activity in Patients with Papillary Thyroid Carcinoma: a Multicenter Retrospective Cohort Study.

Purpose: We aimed to investigate the impact of various factors including radioactive iodine (RAI) activity on the therapeutic response according to the range of serum thyroglobulin (Tg) in patients with papillary thyroid carcinoma (PTC). Methods: A total of 2809 patients were retrospectively enrolled from 24 hospitals. They were divided into four subgroups according to their serum Tg (stimulated Tg, sTg) or anti-Tg antibody (TgAb) levels, measured just before RAI therapy: sTg < 2 ng/mL, 2 ≤ sTg < 10 ng/mL, sTg ≥ 10 ng/mL, and TgAb > 100 IU/mL. The clinicopathologic factors for therapeutic responses, which were classified as acceptable response (AR) or non-AR, were compared in each subgroup. Results: Clinical impact of the pN category on therapeutic response was different among subgroups based on sTg levels (subgroups with sTg < 2 ng/mL (P = 0.057), 2 ≤ sTg < 10 ng/mL (P = 0.032), and sTg ≥ 10 ng/mL (P = 0.001)). The pN category was also a significant factor in the subgroup with TgAb > 100 IU/mL (P = 0.006). The pT category was not associated with therapeutic response regardless of the sTg level. High activities of RAI (≥ 3.70 GBq) were associated with favorable therapeutic responses in only the subgroup with sTg ≥ 10 ng/mL (P = 0.044). Conclusion: Risk factors for response prediction could be repositioned based on the serum Tg before RAI therapy. RAI activity should be determined while considering the serum Tg-aided remnant thyroid or malignant tissues as well as conventional factors. Supplementary Information: The online version contains supplementary material available at 10.1007/s13139-022-00756-4.

In vivo imaging of invasive aspergillosis with 18F-fluorodeoxysorbitol positron emission tomography.

Invasive aspergillosis is a critical complication in immunocompromised patients with hematologic malignancies or with viral pneumonia caused by influenza virus or SARS­CoV­2. Although early and accurate diagnosis of invasive aspergillosis can maximize clinical outcomes, current diagnostic methods are time-consuming and poorly sensitive. Here, we assess the ability of 2-deoxy-2-18F-fluorosorbitol (18F-FDS) positron emission tomography (PET) to specifically and noninvasively detect Aspergillus infections. We show that 18F-FDS PET can be used to visualize Aspergillus fumigatus infection of the lungs, brain, and muscles in mouse models. In particular, 18F-FDS can distinguish pulmonary aspergillosis from Staphylococcus aureus infection, both of which induce pulmonary infiltrates in immunocompromised patients. Thus, our results indicate that the combination of 18F-FDS PET and appropriate clinical information may be useful in the differential diagnosis and localization of invasive aspergillosis.

Precise characterization of a solitary pulmonary nodule using tumor shadow disappearance rate-corrected F-18 FDG PET and enhanced CT.

ABSTRACT: We aimed to characterize solitary pulmonary nodule (SPN) using imaging parameters for F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) or enhanced CT corrected by tumor shadow disappearance rate (TDR) to reflect the tissue density.We enrolled 51 patients with an SPN who underwent PET/CT and chest CT with enhancement. The FDG uptake of SPN was evaluated using maximum standardized uptake value (SUVmax) on PET/CT. The mean Hounsfield unit (HU) for each SPN was evaluated over the region of interest on nonenhanced and enhanced CT images. The change in mean HU (HUpeak-pre) was quantified by subtracting the mean HU of the preenhanced CT from that of the post-enhanced CT. TDR was defined as the ratio of the tumor area, which disappears at a mediastinal window, to the tumor area of the lung window. We investigated which parameters (SUVmax or HUpeak-pre) could contribute to the characterization of SPN classified by TDR value and whether diagnostic performance could be improved using TDR-corrected imaging parameters.For SPN with higher tissue density (TDR <42%, n = 22), high value of SUVmax (≥3.1) was a significant factor to predict malignancy (P = .006). High value of HUpeak-pre (≥38) was a significant factor to characterize SPN (P = .002) with lower tissue density (TDR ≥42%, n = 29). The combined approach using TDR-corrected parameters had better predictive performance to characterize SPN than SUVmax only (P = .031).Applying imaging parameters such as SUVmax or HUpeak-pre in consideration of tissue density calculated with TDR could contribute to accurate characterization of SPN.

Predictive Factors for Skip Lymph Node Metastasis and Their Implication on Recurrence in Papillary Thyroid Carcinoma.

Skip lymph node (LN) metastases in papillary thyroid carcinoma (PTC) belong to N1b classification in the absence of central neck LN involvement. This study aimed to evaluate the predictive factors of skip metastases and their impact on recurrence in PTC patients with pN1b. A total of 334 PTC patients who underwent total thyroidectomy with LN dissection (central and lateral neck compartment) followed by radioactive iodine ablation were included. Patients with skip metastases tended to have a small primary tumor (≤1 cm) and single lateral neck level involvement. Tumor size ≤ 1 cm was an important predictive factor for skip metastases. Univariate analysis for recurrence showed that patients with a central LN ratio > 0.68, lateral LN ratio > 0.21, and stimulated thyroglobulin (Tg) levels > 7.3 ng/mL had shorter RFS (recurrence-free survival). The stimulated Tg level was associated with shorter RFS on multivariate analysis (>7.3 vs. ≤7.3 ng/mL; hazard ratio, 4.226; 95% confidence interval, 2.226-8.022; p < 0.001). Although patients with skip metastases tended to have a small primary tumor and lower burden of lateral neck LN involvement, there was no association between skip metastases and RFS in PTC with pN1b. Stimulated Tg level was a strong predictor of recurrence.

Multimodal Imaging-Based Potential Visualization of the Tumor Microenvironment in Bone Metastasis.

Bone metastasis (BM) is the most common malignant bone tumor and a significant cause of morbidity and mortality for patients with cancer. Compared to other metastatic organs, bone has unique characteristics in terms of the tumor microenvironment (TME). Precise assessments of the TME in BM could be an important step for developing an optimized management plan for patient care. Imaging approaches for BM have several advantages, such as biopsy not being required, multiple site evaluation, and serial assessment in the same sites. Owing to the developments of new imaging tracers or imaging modalities, bone TME could be visualized using multimodal imaging techniques. In this review, we describe the BM pathophysiology, diagnostic principles of major imaging modalities, and clinically available imaging modalities to visualize the TME in BM. We also discuss how the interactions between various factors affecting the TME could be visualized using multimodal imaging techniques.

A Stepwise Approach Using Metastatic Lymph Node Ratio-Combined Thyroglobulin for Customization of [18F]FDG-PET/CT Indication to Detect Persistent Disease in Patients with Papillary Thyroid Cancer.

We investigated whether an indication for [18F]FDG-PET/CT to detect FDG-avid persistent disease (PD) could be identified precisely using the extent of metastatic lymph nodes (MLNs) and serum thyroglobulin (Tg) in papillary thyroid cancer (PTC) patients. This retrospective study included 429 PTC patients who underwent surgery and radioactive iodine (RAI) therapy. [18F]FDG-PET/CT and serum Tg were evaluated just before RAI therapy. The MLN ratio (LNR) was defined as the ratio of the number of MLNs to the number of removed LNs. To derive the LNR-combined criteria, different Tg cut-off values for identifying the PET/CT-indicated group for PD detection were applied individually to subgroups initially classified based on LNR cut-off values. The cut-off values for serum Tg, the number of MLNs, and LNR for a PET/CT indication were 6.0 ng/mL, 5, and 0.51, respectively. Compared to a single parameter (serum Tg, total number of MLNs, and LNR), the LNR-combined criteria showed significantly superior diagnostic performance in detecting FDG-avid PD (p < 0.001). The diagnostic performance of PET/CT in detecting FDG-avid PD was significantly improved when the PET/CT-indicated group was identified through the LNR-combined criteria in a stepwise manner; this can contribute to a customized PET/CT indication in PTC patients.

Change of Therapeutic Response Classification According to Recombinant Human Thyrotropin-Stimulated Thyroglobulin Measured at Different Time Points in Papillary Thyroid Carcinoma.

PURPOSE: We investigated whether response classification after total thyroidectomy and radioactive iodine (RAI) therapy could be affected by serum levels of recombinant human thyrotropin (rhTSH)-stimulated thyroglobulin (Tg) measured at different time points in a follow-up of patients with papillary thyroid carcinoma (PTC). METHODS: A total of 147 PTC patients underwent serum Tg measurement for response assessment 6 to 24 months after the first RAI therapy. Serum Tg levels were measured at 24 h (D1Tg) and 48-72 h (D2-3Tg) after the 2nd injection of rhTSH. Responses were classified into three categories based on serum Tg corresponding to the excellent response (ER-Tg), indeterminate response (IR-Tg), and biochemical incomplete response (BIR-Tg). The distribution pattern of response classification based on serum Tg at different time points (D1Tg vs. D2-3Tg) was compared. RESULTS: Serum D2-3Tg level was higher than D1Tg level (0.339 ng/mL vs. 0.239 ng/mL, P < 0.001). The distribution of response categories was not significantly different between D1Tg-based and D2-3Tg-based classification. However, 8 of 103 (7.8%) patients and 3 of 40 (7.5%) patients initially categorized as ER-Tg and IR-Tg based on D1Tg, respectively, were reclassified to IR-Tg and BIR-Tg based on D2-3Tg, respectively. The optimal cutoff values of D1Tg for the change of response categories were 0.557 ng/mL (from ER-Tg to IR-Tg) and 6.845 ng/mL (from IR-Tg to BIR-Tg). CONCLUSION: D1Tg measurement was sufficient to assess the therapeutic response in most patients with low level of D1Tg. Nevertheless, D2-3Tg measurement was still necessary in the patients with D1Tg higher than a certain level as response classification based on D2-3Tg could change.

Clinical impact of radioactive iodine dose selection based on the number of metastatic lymph nodes in patients with papillary thyroid carcinoma: A multicenter retrospective cohort study.

OBJECTIVE: The aim of this study is to investigate whether the number of metastatic lymph nodes (LNs) could be used as a basis in the radioactive iodine (RAI) dose selection for patients with papillary thyroid carcinoma (PTC). PATIENTS: A total of 595 patients with PTC who received first RAI therapy after total or near-total thyroidectomy and had no evidence of disease in treatment response assessment were retrospectively enroled from five hospitals. The patients were classified into two subgroups based on the number of metastatic LNs (>5). The multivariate Cox-proportional hazard model was performed to identify the significant factors for recurrence prediction in each group as well as all enroled patients. RESULTS: Overall, 22 (3.7%) out of 595 patients had the recurrent disease during the follow-up period. The number of metastatic LNs (>5) was only a significant factor for recurrence prediction in all enroled patients (odds ratio: 7.834, p < .001). In the subgroup with ≤5 metastatic LNs, the presence of extrathyroidal extension was only associated with recurrence (odds ratio: 7.333, p = .024) in multivariate analysis. RAI dose was significantly associated with recurrence rate in which the patients with high-dose RAI (3.7 GBq or higher) had less incidence of recurrence than those with low-dose RAI (1.11 GBq) in the subgroup with more than five metastatic LNs (odds ratio: 6.533, p = .026). CONCLUSIONS: High-dose RAI (≥3.7 GBq) therapy significantly lowered the recurrence rate in patients with more than five metastatic LNs. Therefore, RAI dose should be determined based on the number of metastatic LNs as well as conventional risk factors.

In Vivo Quantitative Vasculature Segmentation and Assessment for Photodynamic Therapy Process Monitoring Using Photoacoustic Microscopy.

Vascular damage is one of the therapeutic mechanisms of photodynamic therapy (PDT). In particular, short-term PDT treatments can effectively destroy malignant lesions while minimizing damage to nonmalignant tissue. In this study, we investigate the feasibility of label-free quantitative photoacoustic microscopy (PAM) for monitoring the vasculature changes under the effect of PDT in mouse ear melanoma tumors. In particular, quantitative vasculature evaluation was conducted based on Hessian filter segmentation. Three-dimensional morphological PAM and depth-resolved images before and after PDT treatment were acquired. In addition, five quantitative vasculature parameters, including the PA signal, vessel diameter, vessel density, perfused vessel density, and vessel complexity, were analyzed to evaluate the influence of PDT on four different areas: Two melanoma tumors, and control and normal vessel areas. The quantitative and qualitative results successfully demonstrated the potential of the proposed PAM-based quantitative approach to evaluate the effectiveness of the PDT method.

Differences in diagnostic impact of dual-tracer PET/computed tomography according to the extrahepatic metastatic site in patients with hepatocellular carcinoma.

OBJECTIVES: We compared the diagnostic performance of C-11 acetate and F-18 fluorodeoxyglucose (FDG) PET/computed tomography (CT) for the detection of extrahepatic metastasis in patients with hepatocellular carcinoma (HCC) and evaluated whether the improvement in the diagnostic performance of dual tracer PET/CT differs by the metastatic site. METHODS: Fifty-eight patients who had extrahepatic metastasis on either C-11 acetate or F-18 FDG PET/CT were enrolled, and 193 metastatic lesions were analyzed in this retrospective study. The metastatic lesions were categorized based on six sites of involvement. According to each involved site, the tracer avidity of the metastatic lesions was compared using the maximum standardized uptake value (SUVmax). RESULTS: Bone was the most frequent categorized metastatic site (44.8%), followed by lymph node (39.7%), lung (34.5%), soft tissue (27.6%), adrenal gland (6.9%), and vascular category (3.4%). C-11 acetate PET/CT showed a higher SUVmax than F-18 FDG PET/CT in metastatic bone lesions (P = 0.003). F-18 FDG uptake was significantly higher than C-11 acetate uptake in metastatic lymph node lesions (P < 0.001). The detection rate of dual tracer PET/CT was significantly higher in the metastatic lung (93.6%) and soft tissue (100%) lesions. However, the diagnostic performance of dual tracer PET/CT was limited in the metastatic bone and lymph node lesions because each tracer's detection rate was very high (bone: 94.6% in C-11 acetate, lymph node: 94.1% in F-18 FDG). CONCLUSIONS: The tracer avidity of metastatic lesions differed according to the involved site. This difference affected the complementary role of dual tracer PET/CT in the diagnosis of extrahepatic metastases in patients with HCC.

18F-fluorodeoxyglucose uptake on PET/computed tomography in association with androgen receptor expression and other clinicopathologic factors in surgically resected triple-negative breast cancer.

OBJECTIVE: To evaluate whether androgen receptor expression in triple-negative breast cancer (TNBC) is associated with F-fluorodeoxyglucose (FDG) uptake and to identify predictive factors of F-FDG uptake in TNBC. METHODS: We retrospectively assessed data of 156 surgically resected primary TNBC in 156 consecutive patients who underwent F-FDG PET/computed tomography between July 2013 and May 2017. Clinicopathologic features, including androgen receptor expression, were categorized and the distribution of maximum standardized uptake value (SUVmax) was compared between the groups. We also evaluated the correlations between the predictive factors and SUVmax. RESULTS: Median SUVmax was higher in the androgen receptor-negative group than in the androgen receptor-positive group (8.8 vs. 7.1, P = 0.026) with negative correlation between androgen receptor and SUVmax (P = 0.041, correlation coefficient (r) = -0.163). On multivariate regression analysis, tumor size (>20 mm), histological grade, Ki-67 (≥14%), and the presence of ductal carcinoma in situ (DCIS) were significantly associated with SUVmax (P < 0.001, P = 0.012, P = 0.017 and P = 0.021, respectively). Tumor size, histological grade and Ki-67 were positively correlated with SUVmax (P < 0.001, r = 0.450; P = 0.004, r = 0.228; P = 0.001, r = 0.269, respectively), while the presence of DCIS showed negative correlation with SUVmax (P < 0.001, r = -0.292). CONCLUSION: Androgen receptor-positive TNBC showed lower F-FDG uptake than androgen receptor-negative triple-TNBC. Tumor size, histological grade, Ki-67 and the presence of DCIS significantly influenced F-FDG uptake in TNBC.

Clinical Impact of F-18 FDG PET-CT on Biopsy Site Selection in Patients with Suspected Bone Metastasis of Unknown Primary Site.

PURPOSE: We investigated the clinical role of F-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) in the identification of the primary site and the selection of the optimal biopsy site in patients with suspected bone metastasis of unknown primary site. METHODS: The patients with suspected bone metastasis who underwent PET-CT for evaluation of primary site were enrolled in this study. The primary sites were identified by the histopathologic or imaging studies and were classified according to the FDG uptake positivity of the primary site. To evaluate the guiding capability of PET-CT in biopsy site selection, we statistically analyzed whether the biopsy site could be affected according to the presence of extra-skeletal FDG uptake. RESULTS: Among 74 enrolled patients, 51 patients had a metastatic bone disease. The primary site was identified in 48 of 51 patients (94.1%). Forty-six patients were eligible to test the association of clinical choice of biopsy site with PET positivity of extra-skeletal lesion. The extra-skeletal biopsies were done in 42 out of 43 patients with positive extra-skeletal uptake lesions. Bone biopsies were inevitably performed in the other three patients without extra-skeletal uptake lesions. The association came out to be significant (Fisher's exact test, P < 0.001). CONCLUSION: F-18 FDG PET-CT significantly contributed not only to identify the primary site but also to suggest optimal biopsy sites in patients with suspected bone metastasis.

Artificial intelligence and lung cancer treatment decision: agreement with recommendation of multidisciplinary tumor board.

BACKGROUND: IBM Watson for Oncology (WFO) is a cognitive computing system helping physicians quickly identify key information in a patient's medical record, surface relevant evidence, and explore treatment options. This study assessed the possibility of using WFO for clinical treatment in lung cancer patients. METHODS: We evaluated the level of agreement between WFO and multidisciplinary team (MDT) for lung cancer. From January to December 2018, newly diagnosed lung cancer cases in Chonnam National University Hwasun Hospital were retrospectively examined using WFO version 18.4 according to four treatment categories (surgery, radiotherapy, chemoradiotherapy, and palliative care). Treatment recommendations were considered concordant if the MDT recommendations were designated 'recommended' by WFO. Concordance between MDT and WFO was analyzed by Cohen's kappa value. RESULTS: In total, 405 (male 340, female 65) cases with different histology (adenocarcinoma 157, squamous cell carcinoma 132, small cell carcinoma 94, others 22 cases) were enrolled. Concordance between MDT and WFO occurred in 92.4% (k=0.881, P<0.001) of all cases, and concordance differed according to clinical stages. The strength of agreement was very good in stage IV non-small cell lung carcinoma (NSCLC) (100%, k=1.000) and extensive disease small cell lung carcinoma (SCLC) (100%, k=1.000). In stage I NSCLC, the agreement strength was good (92.4%, k=0.855). The concordance was moderate in stage III NSCLC (80.8%, k=0.622) and relatively low in stage II NSCLC (83.3%, k=0.556) and limited disease SCLC (84.6%, k=0.435). There were discordant cases in surgery (7/57, 12.3%), radiotherapy (2/12, 16.7%), and chemoradiotherapy (15/129, 11.6%), but no discordance in metastatic disease patients. CONCLUSIONS: Treatment recommendations made by WFO and MDT were highly concordant for lung cancer cases especially in metastatic stage. However, WFO was just an assisting tool in stage I-III NSCLC and limited disease SCLC; so, patient-doctor relationship and shared decision making may be more important in this stage.

Combined role of lymph node ratio and serum thyroglobulin levels in predicting prognosis of papillary thyroid carcinoma.

OBJECTIVES: The aim of this study was to evaluate a prognostic value of the extent of metastatic lymph node combined with TSH-stimulated serum thyroglobulin (sTg) measured just before radioactive iodine (RAI) therapy in patients with papillary thyroid cancer (PTC). METHODS: The retrospective study included 468 patients with PTC who underwent total thyroidectomy with neck dissection and postoperative RAI therapy. The extent of metastatic lymph node was evaluated with the lymph node ratio (LNR) which was defined as the number of metastatic lymph nodes out of the number of total removed lymph nodes. We investigated which factors could significantly predict persistent or recurrent disease (PRD). RESULTS: LNR ≥0.4 (P = 0.002) and sTg ≥6.0 ng/mL (P < 0.001) were associated with PRD in univariate analysis. In multivariate analysis, only male [hazard ratio: 2.35, 95% confidence interval (CI): 1.18-4.66, P = 0.014] and sTg (hazard ratio: 9.35, 95% CI: 4.44-19.67, P < 0.001) were associated with PRD prediction. When we divided patients into two groups (patients with sTg level < 6.0 ng/mL and those with sTg level ≥ 6.0 ng/mL), LNR (≥0.4) was a significant predictor of PRD in patients with sTg <6.0 ng/mL (hazard ratio: 4.38, 95% CI: 1.22-15.72, P = 0.024). CONCLUSIONS: LNR ≥0.4 was a significant predictor of PRD when the sTg level was <6.0 ng/mL. LNR should be used in combination with a relatively low level of serum sTg to predict the prognosis of patients with PTC.