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.

Clinicopathologic risk factors of radioactive iodine therapy based on response assessment in patients with differentiated thyroid cancer: a multicenter retrospective cohort study.

PURPOSE: We investigated whether predictive clinicopathologic factors can be affected by different response criteria and how the clinical usefulness of radioactive iodine (RAI) therapy should be evaluated considering variable factors in patients with differentiated thyroid carcinoma (DTC). METHODS: A total of 1563 patients with DTC who underwent first RAI therapy after total or near total thyroidectomy were retrospectively enrolled from 25 hospitals. Response to therapy was evaluated with two different protocols based on combination of biochemical and imaging studies: (1) serum thyroglobulin (Tg) and neck ultrasonography (US) and (2) serum Tg, neck US, and radioiodine scan. The responses to therapy were classified into excellent and non-excellent or acceptable and non-acceptable to minimize the effect of non-specific imaging findings. We investigated which factors were associated with response to therapy depending on the follow-up protocols as well as response classifications. Multivariate logistic regression analysis was performed to identify factors significantly predicting response to therapy. RESULTS: The proportion of patients in the excellent response group significantly decreased from 76.5 to 59.6% when radioiodine scan was added to the follow-up protocol (P < 0.001). Preparation method (recombinant human TSH vs. thyroid hormone withdrawal) was a significant factor for excellent response prediction evaluated with radioiodine scan (OR 2.129; 95% CI 1.687-2.685; P < 0.001) but was not for other types of response classifications. Administered RAI activity, which was classified as low (1.11 GBq) or high (3.7 GBq or higher), significantly predicted both excellent and acceptable responses regardless of the follow-up protocol. CONCLUSIONS: The clinical impact of factors related to response prediction differed depending on the follow-up protocol or classification of response criteria. A high administered activity of RAI was a significant factor predicting a favorable response to therapy regardless of the follow-up protocol or classification of response criteria.

Myeloid Sarcoma That Infiltrated a Preexisting Sebaceous Lymphadenoma in the Parotid Gland: Diagnostic Challenges and Literature Review.

Myeloid sarcoma (MS) is a rarely encountered extramedullary localized tumor that is composed of immature myeloid cells. We reported an extremely rare case of MS with concurrent bone marrow (BM) involvement that invaded into a preexisting sebaceous lymphadenoma in the parotid gland and neck lymph nodes. Prompted by this case, we also present a literature review of MS invasion into salivary glands. A 62-year-old man was initially diagnosed with carcinoma that arose in a sebaceous lymphadenoma in the parotid gland, through a total parotidectomy with neck dissection. After an extensive histopathological review that included immunohistochemistry, a pathologic diagnosis of MS with infiltration into the sebaceous lymphadenoma with concurrent BM involvement was confirmed. MS is difficult to diagnose accurately; herein, we analyzed the clinical presentations and effectiveness of the various diagnostic methods with a review of the literature. There are 17 cases, including our case, reported in 13 studies. Of the cases in which the salivary glands were affected, 10 involved the parotid gland, six involved the submandibular gland, and one involved both. Isolated invasion of the salivary gland was found in one case of parotid gland invasion and three cases of submandibular gland invasion. In 13 cases, the salivary glands were affected by various other lesions. Although there were no incidences of isolated MS, six patients were diagnosed with secondary MS and eight patients with MS with BM involvement, including this case. The diagnosis of MS is difficult given its rarity, and a high index of suspicion and integrated radiologic and careful histopathologic evaluation are required. Most cases of MS infiltrating the salivary gland might be indicated by the possibility of BM involvement. MS with BM involvement predicts poor prognosis and the need for intensive systemic treatment.

Evaluating the Predictive Ability of Initial Staging F-18 FDG PET/CT for the Prognosis of Non-Hodgkin Malignant Lymphoma Patients Who Underwent Stem Cell Transplantation.

OBJECTIVES: This study aimed to determine the value of clinical prognostic factors and semiquantitative metabolic parameters from initial staging fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) in non-Hodgkin lymphoma (NHL) patients treated with stem cell transplantation (SCT). METHODS: A total of 39 malignant lymphoma patients who underwent initial staging F-18 FDG PET/CT were enrolled in this study. SUVmax, MTV_wb, and TLG_wb were measured during the initial staging PET/CT. Receiver operating characteristic curve (ROC) analysis was adopted to dichotomize continuous variables. Log-rank test and Cox proportional hazard regression analysis were used to evaluate disease-free survival (DFS) rate. RESULTS: Among the 39 patients with malignant lymphoma, 17 (43.6%) had a relapse. For several clinical factors such as age, ECOG performance score, AMC/ALC score, stages, and revised International Prognostic Index score, differences between the two dichotomized groups were statistically insignificant. In univariate analysis, DFS estimates were 71.0 ± 7.8 months and 18.0 ± 5.9 months in high-SUVmax and low-SUVmax group, respectively (P < 0.01). For MTV_wb, DFS estimates were 46.6 ± 12.4 months and 69.1 ± 8.5 months in high-MTV_wb and low-MTV_wb group, respectively (P = 0.12). For TLG_wb, DFS estimates were 65.3 ± 7.5 months and 13.7 ± 8.6 months in high-TLG_wb and low-TLG_wb group, respectively (P = 0.02). In Cox proportional hazard regression analysis, only MTV_wb showed statistical significance (HR 3.01, 95% CI 1.04-8.74, P = 0.04). CONCLUSION: In NHL patients treated with SCT, the MTV_wb of initial staging F-18 FDG PET/CT was an independent prognostic factor.

Correlation of Molecular Subtypes of Invasive Ductal Carcinoma of Breast with Glucose Metabolism in FDG PET/CT: Based on the Recommendations of the St. Gallen Consensus Meeting 2013.

PURPOSE: This study aimed to investigate the relationship between the SUVmax of primary breast cancer lesions and the molecular subtypes based on the recommendations of the St. Gallen consensus meeting 2013. METHODS: Clinical records of patients who underwent F-18 FDG PET/CT for initial staging of invasive ductal carcinoma (IDC) of the breast were reviewed. A total of 183 patients were included. SUVmax was correlated with the molecular subtypes defined by the St. Gallen Consensus Meeting 2013, i.e., luminal A-like (LA), luminal B-like HER2 negative (LBHER2-), luminal B-like HER2 positive (LBHER2+), HER2 positive (HER2+), and triple negative (TN), and with the clinicohistopathologic characteristics. RESULTS: The molecular subtype was LA in 38 patients, LBHER2- in 72, LBHER2+ in 21, HER2+ in 30, and TN in 22. The mean SUVmax in the LA, LBHER2-, LBHER2+, HER2+, and TN groups were 4.5 ± 2.3, 7.2 ± 4.9, 7.2 ± 4.3, 10.2 ± 5.5, and 8.8 ± 7.1, respectively. Although SUVmax differed significantly among these subtypes (p < 0.001), the values showed a wide overlap. Optimal cut-off SUVmax to differentiate LA from LBHER2-, LBHER2+, HER2+ and TN were 5.9, 5.8, 7.5, and 10.2 respectively, with area under curve (AUC) of 0.648, 0.709, 0.833, and 0.697 respectively. The cut-off value of 5.9 yielded the highest accuracy for differentiation between the LA and non-LA subtypes, with sensitivity, specificity, and AUC of 79.4 %, 57.9 %, and 0.704 respectively. CONCLUSION: The SUVmax showed a significant correlation with the molecular subtype. Although SUVmax measurements could be used along with immunohistochemical analysis for differentiating between molecular subtypes, its application to individual patients may be limited due to the wide overlaps in SUVmax.

Clinical Usefulness of F-18 FDG PET/CT in Papillary Thyroid Cancer with Negative Radioiodine Scan and Elevated Thyroglobulin Level or Positive Anti-thyroglobulin Antibody.

PURPOSE: Elevated thyroglobulin (Tg) levels, along with a negative radioiodine scan, present a clinical problem for the diagnosis of recurrence in papillary thyroid cancer (PTC) patients. The purpose of this study was to assess (1) the usefulness of (18)F-fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET)/computed tomography (CT) for PTC patients with negative diagnostic radioiodine scan and elevated serum Tg level or positive anti-thyroglobulin antibody (TgAb), and (2) the effect of endogenous thyroid stimulating hormone (TSH) stimulation (ETS) on detecting recurrence in these circumstances. METHODS: Eighty-four patients with negative diagnostic radioiodine scan and elevated serum Tg or positive TgAb under ETS were included. Correlation with clinicopathological features and recurrence, detectability of FDG PET/CT and cut-off value of serum Tg for recurrence in PTC patients with these circumstance were assessed. In addition, detectability of F-18 FDG PET/CT under ETS and suppression were compared. RESULTS: In Cox regression analysis, only serum Tg level was significantly associated with recurrence (P < 0.001, HR = 1.13; 95 % CI, 1.061-1.208). The cut-off level of Tg was 21.5 ng/mL (AUC, 0.919; P < 0.001) for discriminating the recurrence in the patients with positive PET/CT finding. The sensitivity, specificity, PPV, NPV, and accuracy of F-18 FDG PET/CT for detecting recurrence were 64 %, 94 %, 86 %, 81 %, and 83 %. In the analysis of F-18 FDG PET/CT under ETS, the sensitivity, specificity, PPV, NPV and accuracy was 64 %, 94 %, 88 %, 81 % and 83 %. Those under TSH suppression were 67 %, 92 %, 80 %, 85 % and 83 %. CONCLUSIONS: F-18 FDG PET/CT, although less sensitive, showed high specificity, PPV, NPV, and accuracy and therefore can be useful for the patients with negative diagnostic radioiodine scan and elevated serum Tg or positive TgAb. In addition, FDG PET/CT under ETS does not seem to have an additive role in detecting recurrence in these patients.

Relationships between transporter expression and the status of BRAF V600E mutation and F-18 FDG uptake in papillary thyroid carcinomas.

PURPOSE: The purpose of this study was to evaluate the expression of the glucose transporters GLUT1 and GLUT3 in papillary thyroid carcinomas (PTCs) and to elucidate their relationship with the BRAF V600E mutation and F-18 FDG uptake. MATERIALS AND METHODS: We retrospectively analyzed data of 52 PTC patients (41 women and 11 men; mean age, 52.4 ± 14.5 years). F-18 FDG PET/CT was performed preoperatively, and the maximum standardized uptake value (SUVmax) was calculated. GLUT1/GLUT3 expression was determined immunohistochemically, and the BRAF V600E mutation was detected using DNA sequencing. RESULTS: GLUT1 and GLUT3 were expressed in 82.7% (43/52) and 59.6% (31/52) PTCs, respectively. The BRAF V600E mutation was detected in 65.4% (34/52) PTCs. The odds ratio between GLUT1 expression and the BRAF V600E mutation was 5.2 (95% CI, 1.11-24.05; p < 0.05), and that between GLUT3 expression and the BRAF V600E mutation was 3.8 (95% CI, 1.14-12.53; p < 0.05). The SUVmax of PTCs was significantly higher if they carried the BRAF V600E mutation (11.3 ± 2.0, compared with 5.7 ± 1.4 for wild type BRAF tumors, Mann-Whitney test, p = 0.016). Neither GLUT1 nor GLUT3 expression was significantly associated with the SUVmax of F-18 FDG PET/CT in PTCs. CONCLUSIONS: Our findings confirmed that both GLUT1 and GLUT3 are strongly expressed by PTCs, although their expression was not significantly associated with the SUVmax of F-18 FDG PET/CT. However, GLUT1 and GLUT3 expressions were significantly associated with the presence of the BRAF V600E mutation, and the SUVmax of tumors was significantly higher in the presence of the mutated BRAF gene.

FDG uptake in non-small cell lung cancer is not an independent predictor of EGFR or KRAS mutation status: a retrospective analysis of 206 patients.

PURPOSE: Data in the literature regarding the use of F-FDG avidity of non-small cell lung cancer (NSCLC) as an imaging biomarker to predict the status of epidermal growth factor receptor (EGFR) mutation are conflicting. Association between KRAS mutation and FDG avidity of NSCLC on PET/CT is not well known. We assessed whether the EGFR or KRAS mutation status in NSCLC can be predicted by FDG avidity by performing several different subgroup analyses to better compare with various published results. PATIENTS AND METHODS: After obtaining institutional review board approval, we enrolled patients (1) who had FDG PET/CT performed for staging of NSCLC, (2) with EGFR and KRAS mutational status of tumor identified, and (3) without uncontrolled diabetes. Univariate and multivariate regression analyses were performed to assess the relationship between the independent clinical variables (sex, age, smoking history, tumor histology, tumor size, stage, and SUV-derived variables) and the EGFR and KRAS mutation status. Separate analyses were performed for patients with adenocarcinomas. RESULTS: There were 206 patients (age, 33-88 years; 148 male/58 female; 71 ever-smokers/135 never-smokers; 135 adenocarcinoma/71 squamous cell carcinoma; 22 stage I-II/184 stage III-IV; tumor size, 1.2-15.0 cm; SUVmax, 2.9-36.4; EGFR mutations present in 47; KRAS mutations present in 20). In multivariate analysis, sex, smoking history, histology, and tumor size were significantly associated with EGFR mutation but none of the SUV-derived variables was. Likewise, no correlation was found between the SUV-derived variables and KRAS mutation. CONCLUSIONS: Our results suggest that FDG avidity of NSCLC has no significant clinical value in predicting the EGFR or KRAS mutation status.

Sonographically based diagnosis of contralateral malignancy in preoperative patients with papillary thyroid microcarcinoma.

OBJECTIVES: We aimed to assess the usefulness of sonographically based diagnosis to predict whether contralaterally located dominant thyroid nodules are malignant or benign in patients with known papillary thyroid microcarcinoma. METHODS: We studied 143 patients with primary papillary thyroid microcarcinoma who underwent preoperative thyroid sonography. Each dominant thyroid nodule was prospectively classified into 1 of 5 diagnostic categories by a single radiologist: benign, probably benign, borderline, possibly malignant, and malignant. We calculated the efficacy of sonographic diagnosis for contralateral malignancy by using histopathologic or long-term sonographic follow-up results as reference standards. RESULTS: Of the 143 primary papillary thyroid microcarcinomas, 17 showed satellite carcinomas; hence, the bilaterality rate in all patients was 11.9% (17 of 143). Real-time sonography of the contralateral thyroid yielded no thyroid nodules (n = 55) and benign (n = 52), probably benign (n = 10), borderline (n = 13), possibly malignant (n = 4), and malignant (n = 9) nodules. When the borderline sonographic class was excluded, the sensitivity, specificity, positive and negative predictive values, and accuracy of sonographic diagnosis for detecting contralateral malignancy were 86.7%, 100%, 100%, 98.3%, and 98.5%, respectively. Within individual sonographic classes for the dominant thyroid nodules, the diagnostic accuracy rates for classes IV and V (possibly malignant and malignant) were higher than those for other classes. CONCLUSIONS: Sonographically based diagnosis may be helpful for detection of contralateral malignancy in preoperative patients with papillary thyroid microcarcinoma.

Pre-operative ultrasound diagnosis of nodal metastasis in papillary thyroid carcinoma patients according to nodal compartment.

The aim of this study was to assess the accuracy of ultrasound (US) and individual US features in the diagnosis of nodal metastasis in patients with papillary thyroid carcinoma (PTC) with respect to nodal compartment. US diagnoses and individual US features of nodal metastases with respect to nodal compartment were investigated in 184 consecutive PTC patients who underwent pre-operative US. Histopathologic results were used as a reference standard. One hundred thirty-six of 368 (37.0%) central compartments contained one or more metastatic nodes, whereas 44 of 48 (91.7%) lateral compartments had one or more metastatic nodes. The malignancy rates of suspicious US diagnoses in the central and lateral compartments were 66.3% (53/80) and 93.3% (42/45), respectively. The central and lateral compartments differed significantly in nodal composition, echogenicity, calcification, shape, hilar echogenicity and vascularity. The accuracy of US in the diagnosis of nodal metastases from PTC was lower in the central compartment than in the lateral compartment.

Comparison of T stage, N stage, multifocality, and bilaterality in papillary thyroid carcinoma patients according to the presence of coexisting lymphocytic thyroiditis.

PURPOSE: This study aimed to assess the relationship between coexisting lymphocytic thyroiditis and T-N stages of papillary thyroid carcinoma (PTC) by histopathological analysis. MATERIALS AND METHODS: The study included 653 patients who underwent thyroid surgery for PTC at our hospital. Each case was classified as either Hashimoto's thyroiditis (HT), non-Hashimoto type of lymphocytic thyroiditis (NHLT), or normal according to the histopathology of thyroid parenchyma. Patient age, gender, surgical modality, location, T stage, N stage, multifocality and bilaterality were compared according to the histopathology. RESULTS: The prevalence of coexisting lymphocytic thyroiditis was 25.8% (169/653); HT (7.5%, 49/653) and NHLT (18.3%, 120/653). There were no significant differences in T stage, N stage, multifocality and bilaterality with regard to coexisting lymphocytic thyroiditis, regardless of whether HT and NHLT were considered collectively or discretely. Primary tumor size (p < 0.0001), location (p = 0.0011), N stage (p < 0.0001), multifocality (p < 0.0001) and bilaterality (p < 0.0001) differed significantly according to T stage, and gender (p = 0.0193), primary tumor size (p < 0.0001), T stage (p < 0.0001), multifocality (p < 0.0001) and bilaterality (p < 0.0001) differed significantly according to N stage. CONCLUSIONS: PTC patients with coexisting lymphocytic thyroiditis did not differ from those with normal parenchyma in terms of T stage, N stage, multifocality and bilaterality.

Factors associated with postoperative hypothyroidism after lobectomy in papillary thyroid microcarcinoma patients.

PURPOSE: No previous study regarding the correlation between post-operative thyroid function and underlying thyroid histopathology has been published. This study assessed the relationship between postoperative thyroid function after lobectomy and multiple factors in papillary thyroid microcarcinoma (PTMC) patients. MATERIALS AND METHODS: From January 2010 to December 2010, 338 patients who had undergone thyroid lobectomy for PTMC were enrolled. Patients with pre-operative hyperthyroidism or those with hypothyroidism but no pre-operative serological data were excluded, leaving a cohort of 285 patients. The relationships between post-operative thyroid function (based on successful cessation of thyroxine replacement therapy) and multiple factors (patient age and sex, serological data, the Pre-operative anteroposterior diameter of the thyroid gland, underlying histopathology of the thyroid gland, and number of attempts to stop thyroxine replacement therapy) were analyzed. RESULTS: Out of 285 patients, 157 attempted to stop thyroxine replacement therapy once or twice after lobectomy; 91 successfully stopped thyroxine replacement therapy during the study period. The final histopathologic diagnoses after surgery included Hashimoto's thyroiditis (n = 5), non-Hashimoto type of lymphocytic thyroiditis (n = 17), and normal thyroid parenchyma (n = 135). Pre-operative thyroid-stimulating hormone (TSH) levels differed significantly between patients with postoperative hypothyroidism and those with postoperative euthyroidism (univariate logistic regression analysis, p = 0.0028; multivariate logistic regression analysis, p = 0.0029). No statistically significant differences were found for any other factors. CONCLUSIONS: The study results demonstrated that the Pre-operative TSH level was the only predictor for the development of post-operative hypothyroidism after thyroid lobectomy in PTMC patients.

Benign intranodal thyroid tissue mimicking nodal metastasis in a patient with papillary thyroid carcinoma: A case report.

BACKGROUND: A case of benign intranodal thyroid tissue mimicking nodal metastasis on ultrasound and CT in a patient with papillary thyroid carcinoma has not been reported. METHODS: The clinical, imaging, and histopathological findings of the patient are presented. A 52-year-old woman who underwent ultrasound-guided fine-needle aspiration for 2 small, suspicious thyroid nodules in both lobes at a local clinic was referred to our hospital for surgical treatment. Ultrasound-guided fine-needle aspiration for a suspicious lymph node in the left upper neck was performed. According to the imaging and cytology results, total thyroidectomy and nodal dissection for both central and left lateral nodes were performed. RESULTS: In the histopathology, the lymph node was confirmed as a benign lymph node with intranodal thyroid tissue. CONCLUSION: This case illustrates that benign intranodal thyroid tissue may mimic nodal metastasis on ultrasound or CT in a patient with papillary thyroid carcinoma.

Suspicious sonographic and cytological findings in patients with subacute thyroiditis: Two case reports.

We here report on two cases of suspicious cytological findings upon ultrasound (US)-guided fine-needle aspiration (US-FNA) in patients with subacute thyroiditis (SAT). A 46-year-old woman who underwent US-FNA for a suspicious thyroid nodule in the right lobe at a local clinic was referred to our hospital for surgical treatment. Based on the cytology results, total thyroidectomy was performed. The histopathology findings confirmed the presence of SAT in the right lobe and absence of thyroid malignancy. A 40-year-old woman with a thyroid nodule in the left lobe with suspicious cytological findings upon US-FNA was referred to our hospital for surgical treatment. However, neck US revealed typical sonographic findings of SAT. On follow-up US 3 months later, near complete disappearance of the typical sonographic findings of SAT was observed, while a hypoechoic solid thyroid nodule in the left upper lobe was clearly visualized. Accordingly, US-FNA was performed for the hypoechoic thyroid nodule. Papillary thyroid carcinoma was suspected on the basis of the cytology findings; histopathologically, SAT was confirmed in both thyroid lobes and a papillary thyroid carcinoma was confirmed in the left lobe.

Incidental abnormal FDG uptake in the prostate on 18-fluoro-2-deoxyglucose positron emission tomography-computed tomography scans.

18-fluoro-2-deoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) scans are commonly used for the staging and restaging of various malignancies, such as head and neck, breast, colorectal and gynecological cancers. However, the value of FDG PET/CT for detecting prostate cancer is unknown. The aim of this study was to evaluate the clinical value of incidental prostate 18F-FDG uptake on PET/CT scans. We reviewed 18F-FDG PET/CT scan reports from September 2009 to September 2013, and selected cases that reported focal/diffuse FDG uptake in the prostate. We analyzed the correlation between 18F-FDG PET/CT scan findings and data collected during evaluations such as serum prostate-specific antigen (PSA) levels, digital rectal examination (DRE), transrectal ultrasound (TRUS), and/or biopsy to confirm prostate cancer. Of a total of 18,393 cases, 106 (0.6%) exhibited abnormal hypermetabolism in the prostate. Additional evaluations were performed in 66 patients. Serum PSA levels were not significantly correlated with maximum standardized uptake values (SUVmax) in all patients (rho 0.483, p=0.132). Prostate biopsies were performed in 15 patients, and prostate cancer was confirmed in 11. The median serum PSA level was 4.8 (0.55-7.06) ng/mL and 127.4 (1.06-495) ng/mL in the benign and prostate cancer groups, respectively. The median SUVmax was higher in the prostate cancer group (mean 10.1, range 3.8-24.5) than in the benign group (mean 4.3, range 3.1-8.8), but the difference was not statistically significant (p=0.078). There was no significant correlation between SUVmax and serum PSA, prostatic volume, or Gleason score. 18F-FDG PET/CT scans did not reliably differentiate malignant or benign from abnormal uptake lesions in the prostate, and routine prostate biopsy was not usually recommended in patients with abnormal FDG uptake. Nevertheless, patients with incidental prostate uptake on 18F-FDG PET/ CT scans should not be ignored and should be undergo further clinical evaluations, such as PSA and DRE.

Intratumoral heterogeneity impacts the response to anti-neu antibody therapy.

BACKGROUND: Along with de novo resistance, continued exposure to trastuzumab, an anti-human epidermal growth factor receptor 2 (HER2/neu) antibody, can lead to acquired resistance. In this study, we characterize a new anti-HER2/neu antibody resistant and metastatic mouse breast carcinoma cell line, TUBO-P2J. This cell line was developed during in vivo experiments using the antibody sensitive and non-metastatic tumor line TUBO. In addition, TUBO-P2J was used to establish an intratumoral HER2 heterogenous animal tumor model to evaluate the therapeutic effects of anti-HER2/neu antibody. METHODS: After establishing the cell line, TUBO-P2J was characterized regarding its susceptibility to anti-neu antibody and chemotherapeutics, as well as its metastatic potential in vitro and in vivo. In addition, expression profiles of metastasis related genes were also evaluated. A clinically relevant intratumoral HER2 heterogenous tumor model was established by inoculating mice with tumor cells consisting of TUBO and TUBO-P2J at a ratio of 1,000:1 or 10,000:1. Tumor growth and mouse survival were used to evaluate the therapeutic effects of anti-neu antibody. RESULTS: The TUBO-P2J cell line is a HER2/neu negative and highly metastatic variant of TUBO. This cell line was resistant to anti-neu antibody therapy, and when inoculated subcutaneously, metastasized to the lungs within 14 days. Compared to the parental TUBO cell line, TUBO-P2J displayed an epithelial-mesenchymal transition (EMT) related gene expression profile including: the loss of E-cadherin, and increased Vimentin, Snail, and Twist1 expression. In addition, TUBO-P2J exhibited increased invasion and migration activity, and was resistant to chemotherapy drugs. Finally, mixed tumor implantations experiments revealed that an increased percentage of TUBO-P2J rendered tumors less responsive to anti-neu antibody therapy. CONCLUSION: This study describes a novel model of intratumoral heterogenous metastatic breast cancer in immune competent mice that can be used to develop novel or combined immunotherapies to overcome antibody resistance.

Value of 18F-FDG PET/CT for early prediction of pathologic response (by residual cancer burden criteria) of locally advanced breast cancer to neoadjuvant chemotherapy.

PURPOSE: A relatively new pathologic grading system, called residual cancer burden (RCB) criteria (0 to III), for assessing the response to neoadjuvant chemotherapy (NCT) of breast cancer has been reported to be more accurate than conventional pathologic criteria. This study assesses the value of F-FDG PET/CT in early prediction of chemotherapeutic response determined based on these criteria. PATIENTS AND METHODS: Thirty-six patients with locally advanced breast cancer underwent F-FDG PET/CT before and after the first (just before the second) cycle of NCT. Percentage changes (%△) in SUVmax, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) between F-FDG PET/CT before and after the first cycle of NCT were correlated with RCB index on pathologic specimens after the completion of NCT. RESULTS: The %△SUVmax, %△MTV, and %△TLG in the RCB 0/I group (n = 5) were all significantly larger than those in the RCB II/III group (n = 31) (82.9%, 100%, and 100% vs 45.8%, 83.2%, and 88.0%, respectively, P < 0.01). The sensitivity/specificity/accuracy of the optimal cutoff %△SUVmax, %△MTV, and %△TLG for discriminating RCB 0/I group from RCB II/III group based on the receiver operating characteristic analysis were 80.0%/96.8%/94.4%, 100%/80.6%/83.3%, and 100%/80.6%/83.3%, respectively. The area under the curve for the 3 parameters was 0.923, 0.903, and 0.884, respectively, and not statistically different. CONCLUSIONS: The %Δmetabolic parameters derived from F-FDG PET/CT studies performed before and after the first cycle of NCT in patients with locally advanced breast cancer appear to be useful in early prediction of eventual therapy response determined based on the RCB pathologic grading system.

Characteristics of Metastatic Mediastinal Lymph Nodes of Non-Small Cell Lung Cancer on Preoperative F-18 FDG PET/CT.

PURPOSE: The aim of this study was to evaluate the characteristics of PET and CT features of mediastinal metastatic lymph nodes on F-18 FDG PET/CT and to determine the diagnostic criteria in nodal staging of non-small cell lung cancer. METHODS: One hundred four non-small cell lung cancer patients who had preoperative F-18 FDG PET/CT were included. For quantitative analysis, the maximum SUV of the primary tumor, maximum SUV of the lymph nodes (SUVmax), size of the lymph nodes, and average Hounsfield units (aHUs) and maximum Hounsfield units (mHUs) of the lymph nodes were measured. The SUVmax, SUV ratio of the lymph node to blood pool (LN SUV/blood pool SUV), SUV ratio of the lymph node to primary tumor (LN SUV/primary tumor SUV), size, aHU, and mHU were compared between the benign and malignant lymph nodes. RESULTS: Among 372 dissected lymph node stations that were pathologically diagnosed after surgery, 49 node stations were malignant and 323 node stations benign. SUVmax, LN SUV/blood pool SUV, and size were significantly different between the malignant and benign lymph node stations (P < 0.0001). However, there was no significant difference in LN SUV/primary tumor SUV (P = 0.18), mHU (P = 0.42), and aHU (P = 0.98). Using receiver-operating characteristic curve analyses, there was no significant difference among these three variables (SUVmax, LN SUV/blood pool SUV, and size). The optimal cutoff values were 2.9 for SUVmax, 1.4 for LN SUV/blood pool SUV, and 5 mm for size. When the cutoff value of SUVmax ≥2.9 and size ≥5 mm were used in combination, the positive predictive value was 44.2 %, and the negative predictive value was 90.9 %. When we evaluated the results based on the histology of the primary tumor, the negative predictive value was 92.3 % in adenocarcinoma (cutoff values of SUVmax ≥2.3 and size ≥5 mm) and 97.2 % in squamous cell carcinoma (cutoff values of SUVmax ≥3.6 and size ≥8 mm), separately. CONCLUSIONS: In the lymph node staging of non-small cell lung cancer, SUVmax, LN SUV/blood pool SUV, and size show statistically significant differences between malignant and benign lymph nodes. These variables can be used to differentiate malignant from benign lymph nodes. The combination of the SUVmax and size of lymph node might have a good negative predictive value.