Prognostic Value of Metabolic Tumor Volume Measured by <Superscript>18</Superscript>F-Fluorodeoxyglucose Positron Emission Tomography in Patients with Esophageal Carcinoma

Purpose  

The aim of this study was to evaluate the prognostic value of metabolic tumor volume (MTV) measured by ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) in patients with esophageal carcinoma.     

Prognostic Impact of Clinicopathological Features and Expression of Biomarkers Related to 18F-FDG Uptake in Esophageal Cancer

Purpose

To analyze the association between pretreatment 18-F-fluoro-deoxyglucose (FDG) uptake and characteristics of aggressive tumor biology in predicting outcome in esophageal cancer (EC).

Methods

Tumor FDG-uptake was measured by maximum standardized uptake values (SUV_max) in 47 patients undergoing esophagectomy with curative intent. ROC analyses were used to predict an optimal SUV_max cutoff for survival. Expression of hexokinase-II (HK-II), glucose transporter I (GLUT-I), hypoxia inducible factor-1α (HIF-Iα), vascular endothelial growth factor-C (VEGF-C), p53, and proliferative activity (Ki-67) were correlated with SUV_max values and clinicopathological characteristics.

Results

A SUV_max > 3.67 predicted a significantly lower disease-free survival (DFS) and distant recurrence-free survival (p = 0.022 and p = 0.005). High HK-II expression was correlated with reduced SUV_max values (p = 0.002) and was significantly higher in esophageal adenocarcinoma compared with squamous cell carcinoma (p = 0.005). Preoperative high FDG uptake in primary tumors was associated with nodal metastases (pN1; Spearman correlation 0.39, p = 0.01). We found no positive correlation between SUV_max and GLUT-1, HK-1, HIF-Iα 1, VEGF-C, p53, and Ki-67 expression.

Conclusions

High preoperative FDG-uptake strongly predicts poor survival outcome and is associated with lymph node metastases in EC patients. HK-II expression was related to SUV_max and DFS.     

Dual-Time <Superscript>18</Superscript>F-FDG PET/CT Imaging in Initial Locoregional Staging of Breast Carcinoma: Comparison with Conventional Imaging and Pathological Prognostic Factors

The aims of this retrospective study were to consider the diagnostic role of dual-time ¹⁸F-fluorodeoxyglucose positron emission tomography and computed tomography (¹⁸F-FDG PET/CT) in detection of breast carcinoma and axillary lymph node (ALN) status and to evaluate the primary tumor ¹⁸F-FDG uptake pattern. Preoperative staging was performed by ¹⁸F-FDG PET/CT in 78 female patients with breast carcinoma. Conventional imaging results were evaluated by breast magnetic resonance imaging (MRI) of 79 lesions in 78 patients, bilateral mammography (MMG) of 40 lesions in 40 patients, and breast ultrasonography (USG) of 47 lesions in 46 patients. The primary tumor detection rate using ¹⁸F-FDG PET/CT was higher than those using MRI, USG, and MMG. The sensitivity and specificity of ¹⁸F-FDG PET/CT scans for detecting multifocality were higher than those of MRI. The specificity of ALN metastasis detection with MRI was higher than that with ¹⁸F-FDG PET/CT, but ¹⁸F-FDG PET/CT had higher sensitivity. Higher ¹⁸F-FDG uptake levels were detected in patients with ALN metastasis, histologic grade 3, estrogen–progesterone-negative receptor status, lymphatic invasion, and moderate to poor prognostic groups. There was no statistical difference for the retention index in categorical pathological parameters except for progesterone-negative status. In conclusion, ¹⁸F-FDG PET/CT scans may be a valuable imaging technique for evaluating primary tumor and axillary status in staging breast carcinoma and ¹⁸F-FDG uptake may be a prognostic factor that indicates aggressive tumor biology and poor prognosis. Dual-time imaging in breast carcinoma staging may not be used for predicting pathological criteria and the aggressiveness of primary lesions.     

Accuracy of MRI and <Superscript>18</Superscript>F-FDG PET/CT for Restaging After Preoperative Concurrent Chemoradiotherapy for Rectal Cancer

Background  

Performing a restaging work-up with magnetic resonance imaging (MRI) and ¹⁸F-fluorodeoxyglucose-positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) can provide information about the effects that are related to preoperative concurrent chemoradiotherapy (CCRT). The purpose of the present study was to investigate the accuracy of MRI and ¹⁸F-FDG PET/CT for restaging after preoperative CCRT for rectal cancer.     

Relationship Between <Superscript>18</Superscript>F-fluorodeoxyglucose Accumulation and the <Emphasis Type="Italic">BRAF</Emphasis><Superscript>V600E</Superscript> Mutation in Papillary Thyroid Cancer

Background

To determine whether ¹⁸F-fluoro-2-deoxyglucose (¹⁸F-FDG)-PET/CT is useful for predicting the BRAF ^V600E mutation status of a primary papillary thyroid carcinoma (PTC).

Methods

A retrospective analysis was performed in 108 patients who underwent ¹⁸F-FDG positron emission tomography–computed tomography (PET/CT) for staging before thyroidectomy and BRAF analysis in biopsy-confirmed PTC. The maximum standardized uptake value (SUV_max) of the primary tumor was calculated according to FDG accumulation. Univariate and multivariate analyses were performed to assess the association between the SUV_max and clinicopathological variables.

Results

The BRAF ^V600E mutation was detected in 71 of 108 (65.7%) patients. In all subjects, the tumor size and BRAF ^V600E mutation were independently related to the SUV_max according to multivariate analyses (P = 0.002 and 0.007, respectively). The SUV_max was significantly higher in tumors with the BRAF ^V600E mutation than in tumors with wild-type BRAF (10.24 ± 11.89 versus 4.02 ± 3.86; P = 0.007). In the tumor size >1 cm subgroup, the BRAF ^V600E mutation was the only factor significantly associated with the SUV_max (P = 0.016). A SUV_max cutoff level of 4.9 was determined to be significant for predicting the BRAF ^V600E mutation status (sensitivity 77.4%, specificity 100.0%, area under the curve 0.929; P < 0.0001) according to ROC curve analysis.

Conclusions

The BRAF ^V600E mutation is independently associated with high ¹⁸F-FDG uptake in PTC, especially in those with a tumor size >1 cm.

     

CD133<Superscript>+</Superscript>CD44<Superscript>+</Superscript> Population Efficiently Enriches Colon Cancer Initiating Cells

Background  Previous reports have demonstrated that CD133⁺ cells or CD44⁺ cells might be cancer initiating cells (CIC) of colon cancer. However, the association between the two cell types is unclear. In this study, we evaluated the tumorigenicity of each population of human colon cancer divided by CD133 and CD44 using non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. Methods  Using the colon cancer cell lines HT29 and Caco2 we evaluated the change of expression status of CD133 or CD44 by a treatment with sodium butyrate (NaBT) that can induce cellular differentiation. Next, we prepared ten clinical samples of colon cancer and analyzed the expression and tumorigenicity of CD133 and CD44. Results  With NaBT treatment, CD44 expression was greatly downregulated in both HT29 and Caco2 (HT29: nontreatment versus treatment; 77.8% versus 0.6%, Caco2: 14.0% versus 0.4%, respectively), more than CD133 expression (HT29: nontreatment versus treatment; 90.1% versus 67.7%, Caco2: 98.9% versus 76.3%, respectively). In clinical samples, the percentages of CD133⁺ cells and CD44⁺ cells varied from 0.3% to 82.0% (mean 35.5%), and from 11.5% to 58.4% (mean 30.0%), respectively. Subcutaneous injection of CD133⁺ or CD44⁺ cells made a tumor in all mice (3/3 and 4/4, respectively). The combined analysis of CD133 and CD44 revealed that only the CD133⁺CD44⁺ population had the ability to produce a tumor (3/3). Conclusion  The findings demonstrate that, at present, the CD133⁺CD44⁺ population may be the best to identify tumor initiating cells of human colon cancer. Naotsugu Haraguchi: Awardee of Research Resident Fellowship from the Foundation for Promotion of Cancer Research (Japan) for the 3^rd Term Comprehensive 10- Year Strategy for Cancer Control.     

Combined [<Superscript>18</Superscript>F]Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography (FDG-PET/CT) for Detection of Recurrent, <Superscript>131</Superscript>I-Negative Thyroid Cancer

Background Whole-body ¹³¹I scintigraphy (WBS) and serial thyroglobulin measurement (Tg) are standard methods for detecting thyroid cancer recurrence after total/near total thyroidectomy and ¹³¹I ablation. Some patients develop elevated Tg (Tg-positive) or there is clinical suspicion of recurrence, but WBS are negative (WBS-negative). This may reflect non-iodine-avid recurrence or metastasis. In 2002, the Centers for Medicare and Medicaid Services (CMS) approved positron emission tomography with [¹⁸F]fluorodeoxyglucose (FDG-PET) for Tg-positive/WBS-negative patients with follicular-cell-origin thyroid cancer. Limited data are available regarding the performance of combined FDG-PET/computed tomography (FDG-PET/CT) for detecting recurrent thyroid cancer in WBS-neg patients. Methods This retrospective review of prospectively collected data analyzed 65 patients who had FDG-PET/CT for suspected thyroid cancer recurrence (April 1998–August 2006). Patients were WBS-negative but were suspected to have recurrence based on Tg levels or clinical grounds. Suspected FDG-PET/CT abnormalities were reported as benign or malignant. Lesions were ultimately declared benign or malignant by surgical pathology or clinical outcome (disease progression). Results Of 65 patients who underwent FDG-PET/CT, 47 had positive FDG-PET/CT. Of the positive FDG-PET/CT, 43 studies were true positives, with 21 (49%) confirmed pathologically by surgical resection. The four false positives (3/4 confirmed pathologically) included an infundibular cyst, an inflamed supraclavicular cyst, pneumonitis, and degenerative disc disease. Of the 18 FDG-PET/CT studies that were negative, 17 were true negatives and one was a false negative (metastatic papillary carcinoma). Thus, FDG-PET/CT demonstrated a patient-based sensitivity of 98%, specificity of 81%, positive predictive value of 91%, and negative predictive value of 94%. Conclusions FDG-PET/CT is useful for detecting thyroid cancer recurrence in WBS-negative patients, and can assist decision making.     

<Superscript>99m</Superscript>Tc-HDP bone scintigraphy and <Superscript>18</Superscript>F-sodiumfluoride PET/CT in primary staging of patients with prostate cancer

Introduction/Aim

Correct staging of patients with prostate cancer is important for treatment planning and prognosis. Although bone scintigraphy with ^99mTc-phosphonates (BS) is generally advised for staging by guidelines in high risk prostate cancer, this imaging technique is hampered by a high rate of inconclusive results and moderate accuracy. Potentially better imaging techniques for detection of bone metastases such as ¹⁸F-sodiumfluoride PET/CT (NaF PET/CT) are therefore being evaluated. In this observational cohort study we evaluate the performance and clinical impact of both BS and NaF PET/CT in primary staging of patients with prostate cancer.

Methods

The first of two cohorts consisted of patients who received a BS while the second included patients who received a NaF PET/CT for primary staging of prostate cancer. For both cohorts the number of positive, negative and equivocal findings, calculated diagnostic performance of the imaging modality in terms of sensitivity and specificity, as well as the impact on clinical management were studied. The ranges of the diagnostic performance were calculated both assuming that equivocal findings were positive and assuming that they were negative for bone metastases. For the NaF PET/CT cohort the number of patients with signs of lymph node metastases on low dose CT were also recorded, including the impact of these findings on clinical management.

Results

One-hundred-and-four patients underwent NaF PET/CT, whereas 122 patients underwent BS. Sensitivities of 97–100 and 84–95% and specificities of 98–100 and 72–100% were found on a patient basis for detection of bone metastases with NaF PET/CT and BS, respectively. Equivocal findings warranted further diagnostic procedures in 2% of the patients in the NaF cohort and in 16% in the BS cohort. In addition NaF PET/CT demonstrated lymph node metastases in 50% of the included patients, of which 25% showed evidence of lymph node metastases only.

Conclusion

Our data indicate better diagnostic performance of NaF PET/CT compared to BS for detection of bone metastases in primary staging of prostate cancer patients. Less equivocal findings are encountered with NaF PET/CT. Moreover, NaF PET/CT has additional value over BS since lymph node metastases are encountered frequently.

     

Value of <Superscript>123</Superscript>I-Subtraction and Single-Photon Emission Computed Tomography in Addition to Planar <Superscript>99m</Superscript>Tc-MIBI Scintigraphy Before Parathyroid Surgery

Purpose To find out if single-photon emission computed tomography (SPECT) and ¹²³I-subtraction can enhance the findings of ^99mTc-methoxyisobutylisonitrile (MIBI) scintigraphy for the preoperative localization of parathyroid (PT) tumors. Methods Among the 111 consecutive patients who underwent preoperative planar ^99mTc-MIBI scintigraphy for hyperparathyroidism (HPT), 64 underwent delayed SPECT, and 17 underwent ¹²³I-subtraction. Two independent blinded experts scored the topographical localization, diagnostic confidence, and impact of each diagnostic modality on the surgical strategy. Results For adenomas, ^99mTc-MIBI scintigraphy had a sensitivity of 77% with a positive predictive value (PPV) of 83%. SPECT did not affect the sensitivity or PPV, but it increased the diagnostic confidence and changed the surgical strategy in 21% of the patients. ¹²³I-subtraction increased the sensitivity from 64% to 82%, but decreased the PPV from 88% to 82%. In hyperplastic glands, ^99mTc-MIBI scintigraphy had a sensitivity of 47% and a PPV of 95%. When ^99mTc-MIBI scintigraphy was combined with SPECT and ¹²³I-subtraction, the results were 44%/10% and 52%/92%, respectively. Both SPECT and ¹²³I-subtraction decreased the diagnostic confidence. Conclusions Adding SPECT to ^99mTc-MIBI scintigraphy improved the surgical decision for parathyroid adenomas. The addition of ¹²³I-subtraction was of limited value. For hyperplastic glands, ^99mTc-MIBI scintigraphy was relatively ineffective, even with the addition of SPECT or ¹²³I-subtraction.     

The Added Diagnostic Value of <Superscript>18</Superscript>F-Fluorodihydroxyphenylalanine PET/CT in the Preoperative Work-Up of Small Bowel Neuroendocrine Tumors

Background

The precise localization of the primary tumor and/or the identification of multiple primary tumors improves the preoperative work-up in patients with small bowel (SB) neuroendocrine tumor (NET). The present study assesses the diagnostic value of ¹⁸F-fluorodihydroxyphenylalanine (¹⁸F-FDOPA) positron emission tomography/computed tomography (PET/CT) during the preoperative wok-up of SB NETs.

Methods

Between January 2010 and June 2017, all consecutive patients with SB NETs undergoing preoperative ¹⁸F-FDOPA PET/CT and successive resection were analyzed. Preoperative work-up included computed tomography (CT), somatostatin receptor scintigraphy (SRS), and ¹⁸F-FDOPA PET/CT. Sensitivity and accuracy ratio for primary and multiple tumor detection were compared with data from surgery and pathology.

Results

There were 17 consecutive patients with SB NETs undergoing surgery. Nine patients (53%) had multiple tumors, 15 (88%) metastatic lymph nodes, 3 (18%) peritoneal carcinomatosis, and 9 patients (53%) liver metastases. A total of 70 SB NETs were found by pathology. Surgery identified the primary in 17/17 (100%) patients and recognized seven of 9 patients (78%) with multiple synchronous SB. Preoperatively, ¹⁸F-FDOPA PET/CT displayed a statistically significant higher sensitivity for primary tumor localization (100 vs. 23.5 vs. 29.5%) and multiple tumor detection (78 vs. 22 vs. 11%) over SRS and CT. Compared with pathology, ¹⁸F-FDOPA PET/CT displayed the highest accuracy ratio for number of tumor detected over CT and SRS (2.0?±?2.2 vs. 0.4?±?0.7 vs. 0.6?±?1.5, p?=?0.0003).

Conclusion

¹⁸F-FDOPA PET/CT significantly increased the sensitivity and accuracy for primary and multiple SB NET identification. ¹⁸F-FDOPA PET/CT should be included systematically in the preoperative work-up of SB NET.

     

Solid-State Quantitative <Superscript>1</Superscript>H and <Superscript>31</Superscript>P MRI of Cortical Bone in Humans

Magnetic resonance imaging (MRI) plays a pivotal role for assessment of the musculoskeletal system. It is currently the clinical modality of choice for evaluation of soft tissues including cartilage, ligaments, tendons, muscle, and bone marrow. By comparison, the study of calcified tissue by MRI is still in its infancy. In this article, we review the potential of the modality for assessment of cortical bone properties known to be affected in degenerative bone disease, with focus on parameters related to matrix and mineral densities, and porosity, by means of emerging solid-state ¹H and ³¹P MRI techniques. In contrast to soft tissues, the MRI signal in calcified tissues has very short lifetime, on the order of 100 μs to a few milliseconds, demanding customized imaging approaches that allow capture of the signal almost immediately after excitation. The technologies described are suited for quantitatively imaging human cortical bone in specimens as well as in vivo in patients on standard clinical imagers, yielding either concentrations in absolute units when measured against a reference standard, or more simply, in the form of surrogate biomarkers. The two major water fractions in cortical bone are those of collagen-bound and pore water occurring at an approximately 3:1 ratio. Collagen-bound water density provides a direct quantitative measure of osteoid density. While at an earlier stage of development, quantification of mineral phosphorus by ³¹P MRI yields mineral density and, together with knowledge of matrix density, should allow quantification of the degree of bone mineralization.     

The Impact of <Superscript>18</Superscript>F-Fluorodeoxyglucose Positron Emission Tomography Positive Lymph Nodes on Postoperative Recurrence and Survival in Resectable Thoracic Esophageal Squamous Cell Carcinoma

Background  

Induction therapy is not always beneficial for all patients. Therefore, it is important to identify the patients with a high rate of recurrence. The occurrence of lymph node metastases (LNMs) strongly influences the postoperative survival in patients with esophageal cancer. We investigated the usefulness of an LN evaluation by initial ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in prediction of postoperative recurrence for patients with resectable esophageal squamous cell carcinoma (ESCC).     

18F-FDG Uptake at Initial Staging of the Adrenocortical Cancers: A Diagnostic Tool but Not of Prognostic Value

Background

Adrenocortical carcinoma (ACC) is a rare cancer for which little level evidence exists to guide management. ¹⁸F-FDG PET (¹⁸F-fluorodeoxyglucose positron emission tomography) is an increasingly used diagnostic tool in patients with suspicious or indeterminate adrenal tumors. In some other solid tumors, ¹⁸F-FDG PET may offer prognostic information that can guide optimal patient treatment. The aim of the present study was to evaluate whether preoperative ¹⁸F-FDG PET based on SUVs assessments has a prognostic value in ACC patients.

Methods

A retrospective analysis was performed in patients who underwent ¹⁸F-FDG PET/CT for the evaluation of ACC. Inclusion criteria were an unequivocal diagnosis of ACC; all data from primary diagnosis available; ¹⁸F-FDG PET/CT performed prior to surgery or other treatment of the primary tumor; a minimum of 6-months follow-up for surviving patients. All ¹⁸F-FDG PET/CT procedures were reinterpreted in a blind fashion.

Results

Thirty-seven patients (23 without metastasis [M0], 14 with metastasis [M1]) fulfilled the study criteria. Median uptake values were tumor standardized uptake values (SUV)_max = 11 (range: 3–56) and a tumor/liver SUV_max ratio = 4.2 (range: 1.3–15). Median follow-up was 20 months. Although classic risk factors (tumoral stage, Weiss score) were associated with poor outcome, there was no correlation between primary tumor FDG uptake with overall survival (OS) and disease free survival (DFS) in M0 patients and with overall survival in M1 patients. ¹⁸F-FDG uptake correlated inconsistently with sinister histological features, such as atypical mitoses or necrosis.

Conclusions

At initial staging, primary tumor FDG uptake in ACC patients does not correlate with OS and DFS at 2 years. Patient prognosis and treatment strategy should not be based on uptake values.     

MRI and <Superscript>18</Superscript>FDG-PET in the assessment of bone marrow infiltration of the spine in cancer patients

The aim of this study was to evaluate the diagnostic value of MRI and ¹⁸FDG-PET in bone marrow infiltration of the spine due to metastases of solid tumours and lymphoma in cancer patients. In 35 cancer patients (solid tumours n = 26, lymphoma n = 9) MRI of the spine and ¹⁸FDG-PET were reviewed and the detectability of metastases, infiltration of the spine, extent of disease, and therapeutic implications were compared. In 8/35 cases (23%) imaging technique showed concordantly no bone marrow infiltration. In 19/35 patients (54%), both MRI and ¹⁸FDG-PET revealed bone marrow infiltration of the axial skeleton. In 12/19 patients (63%), MRI showed more extensive disease which lead to subsequent therapy. The imaging findings of MRI and ¹⁸FDG-PET were discordant in 8/35 cases (23%). ¹⁸FDG-PET was false positive in two patients. In six patients, ¹⁸FDG-PET failed to detect bone metastases and bone marrow infiltration of the spine, which was detected by MRI and proven by clinical follow-up with subsequent therapy in two cases. MRI is more sensitive and specific than ¹⁸FDG-PET detecting bone marrow metastases and infiltration of the spine and has a great impact in staging cancer patients.     

Prognostic value of post-treatment metabolic tumor volume from <Superscript>11</Superscript>C-methionine PET/CT in recurrent malignant glioma

We investigated the diagnostic and prognostic significance of metabolic parameters from ¹¹C-methionine (MET) positron emission tomography (PET) in patients with malignant glioma. The MET-PET was examined in 42 patients who had been previously treated with adjuvant treatment for malignant glioma. Both ratios of maximal MET uptake of the tumors to those of the contralateral normal gray matter (T/N ratio) and metabolic tumor volume (MTV) were estimated in each lesion. The diagnostic performance for recurrence was investigated in all enrolled patients. A definitive diagnosis was done with pathologic confirmation or clinical follow-up. Among recurrent patients, we evaluated the prognostic value of metabolic parameters (T/N ratio and MTV) as well as clinical factors. Among 42 patients, 35 patients were revealed with recurrence. Both T/N ratios (p?=?0.009) and MTV (p?=?0.001) exhibited statistical significance to differentiate between recurrence and post-treatment radiation effect. A T/N ratio of 1.43 provided the best sensitivity and specificity for recurrence (91.4 and 100 %, respectively), and a MTV of 6.72 cm³ provided the best sensitivity and specificity (77.1 % and 100 %, respectively). To evaluate the prognostic impact, different cutoffs of MTV were examined in patients with recurrent tumor and a threshold of 60 cm³ was determined as a best cutoff value to separate the patients in two prognostic groups. Univariate analysis revealed improved overall survival (OS) for patients with Karnofsky performance scale (KPS) score ≥70 (p?<?0.001) or MTV <60 cm³ (p?=?0.049). Multivariate analysis showed that patients with KPS score ≥70 (p?<?0.001; hazard ratio?=?0.104; 95 % CI, 0.029–0.371) or MTV?<?60 cm³ (p?=?0.031; hazard ratio?=?0.288; 95 % CI, 0.093–0.895) were significantly associated with a longer OS. However, T/N ratio was not correlated with patients’ outcome. Metabolic parameters had the diagnostic value to differentiate recurrence from post-treatment radiation effect. Compared with T/N ratio, MTV was an independent significant prognostic factor with KPS score in patients with recurrent tumor. Our study had a potential to manage these patients according to prognostic information using MET-PET.