Prognostic Value of Volume-Based Metabolic Parameters Measured by 18F-FDG PET/CT of Pancreatic Neuroendocrine Tumors

Purpose

To date, the prognostic value of ¹⁸F-FDG PET/CT for patients with pancreatic neuroendocrine tumors (PNETs) has not been well characterized. We investigated the prognostic value of volumetric parameters using ¹⁸F-FDG PET/CT in this patient population.

Methods

We retrospectively reviewed 20 cases of pathologically proven PNET in patients who had undergone pre-therapeutic ¹⁸F-FDG PET/CT. PET parameters including maximum and average standardized uptake values (SUV_max, SUV_ave), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor were measured using a threshold SUV to determine the boundaries of the tumors. Univariate and multivariate survival analyses were performed with adjustments for PET parameters and other clinical values.

Results

The median clinical follow-up was 22.3 (range, 1.2–95.4) months. Cancer-related death occurred in 5 of 20 patients (25 %). Patients had clinical or pathological stages of I in seven patients, II in six patients, III in three patient, and IV in four patients. According to the WHO histological classification of subtypes, 3 patients exhibited well-differentiated PNETs, 13 patients had well-differentiated endocrine carcinomas, and 4 had poorly differentiatedendocrine carcinomas. Univariate analysis showed that tumor size (p = 0.028), AJCC stage (p = 0.009), T stage (p = 0.028), M stage (p = 0.029), treatment modality (p = 0.045), MTV (p = 0.003) and TLG (p = 0.027) were significant predictors of overall survival. On multivariate analysis, MTV (HR = 10.859, p = 0.031) was a significant independent predictor of overall survival along with the AJCC stage (HR = 11.556, p = 0.027).

Conclusion

In patients with PNETs, the MTV of the primary tumor as measured by ¹⁸F-FDG PET/CT along with the AJCC stage may be a significant independent prognostic factor for overall survival.     

The Prognostic Value of 18F-FDG PET/CT for Early Recurrence in Operable Breast Cancer: Comparison with TNM Stage

Purpose

We evaluated whether the maximum standardized uptake values (SUV_max) of primary tumor from the initial staging by ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) of patients with breast cancer could identify patients at risk for early recurrence within 2 years, particularly in comparison to the American Joint Committee on Cancer (AJCC) stage.

Methods

We reviewed the staging ¹⁸F-FDG PET/CT images of patients with primary breast cancer and their medical records. The SUV_max of the primary tumor was measured. The presence or absence of FDG uptake in the axillary lymph node (ALN) was also assessed. The patient’s pathologic primary tumor stage (pT), pathologic regional lymph node stage (pN), stage grouping, age, estrogen receptor (ER) and progesterone receptor (PR) status, and neoadjuvant chemotherapy history were evaluated with the FDG uptake parameters for recurrence within 2 years following the end of first-line therapy.

Results

Recurrence within 2 years was present in 9.1 % (n = 40) out of the 441 patients assessed. The FDG uptake in ALN, pT, pN, stage grouping and neoadjuvant chemotherapy history were prognostic for early recurrence, while primary tumor SUV_max, age, and ER or PR status were not significant on logistic regression. On multivariate analysis, only the stage grouping (odds ratio 2.79; 95 % CI 1.73, 4.48; p < 0.0001) and neoadjuvant chemotherapy history (odds ratio 2.70; 95 % CI 1.22, 5.98; p = 0.0141) could identify patients at increased risk for recurrence within 2 years.

Conclusions

Primary tumor FDG uptake measured by SUV_max, and visual assessment of FDG uptake in the ALN in the initial staging PET/CT of patients with breast cancer may not have additional prognostic value compared with the AJCC stage grouping for early recurrence.     

Pretreatment F-18 FDG PET/CT Parameters to Evaluate Progression-Free Survival in Gastric Cancer

Purpose

We performed this study to evaluate the predictive value of pretreatment F-18 FDG PET/CT for progression-free survival (PFS) in patients with gastric cancer.

Methods

Of 321 patients with a diagnosis of gastric cancer, we retrospectively enrolled 97 patients (men:women = 61:36, age 59.8 ± 13.2 years), who underwent pretreatment F-18 fluoro-2-deoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) from January 2009 to December 2009. Maximum standardized uptake value (SUVmax) was measured for each case with detectable primary lesions. In the remaining non-detectable cases, SUVmax was measured from the corresponding site seen on gastroduodenoscopy for analysis. In subgroup analysis, metabolic tumor volume (MTV) was measured in 50 patients with clearly distinguishable primary lesions. SUVmax, stage, depth of tumor invasion and presence of lymph node metastasis were analyzed in terms of PFS. Receiver operating characteristic (ROC) curves were used to find optimal cutoff values of SUVmax and MTV for disease progression. The relationship between SUVmax, MTV and PFS was analyzed using the Kaplan-Meier with log-rank test and Cox’s proportional hazard regression methods.

Results

Of 97 patients, 15 (15.5 %) had disease progression. The mean follow-up duration was 29.6 ± 10.2 months. The mean PFS of low SUVmax group (≤5.74) was significantly longer than that of the high SUVmax group (>5.74) (30.9 ± 8.0 vs 24.3 ± 13.6 months, p = 0.008). In univariate analysis, stage (I vs II, III, IV), depth of tumor invasion (T1 vs T2, T3, T4), presence of lymph node metastasis and SUVmax (>5.74 vs ≤5.74) were significantly associated with recurrence. In multivariate analysis, high SUVmax (>5.74) was the only poor prognostic factor for PFS (p = 0.002, HR 11.03, 95 % CI 2.48–49.05). Subgroup multivariate analysis revealed that high MTV (>16.42) was the only poor prognostic factor for PFS (p = 0.034, HR 3.59, 95 % CI 1.10–11.71).

Conclusion

In gastric cancer, SUVmax measured by pretreatment F-18 FDG PET/CT has a significant predictive value for PFS. In addition, if MTV is measurable, high MTV is an independent factor for disease progression.     

Differential Diagnosis of Borderline Ovarian Tumors from Stage I Malignant Ovarian Tumors using FDG PET/CT

Purpose

Borderline ovarian tumors (BOTs) are more common in young women of reproductive age, and exhibit a better prognosis than malignant ovarian tumors (MOTs). Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) were compared in their ability to differentiate BOTs from stage I MOTs.

Methods

Among 173 patients who had preoperative FDG PET/CT due to ovarian neoplasms between November 2006 and March 2009, there were 13 patients with BOTs or stage I MOTs. For differential diagnosis of the two tumors, cancer antigen-125 (CA-125) level, the longest diameter of tumors, metabolic indices including maximum standardized uptake value (SUV_max), and volumetric indices including metabolic tumor volume (MTV) were compared, respectively.

Results

The BOT group (n = 7) was comprised of five mucinous and two serous tumors, and the MOT group (n = 6) was comprised of three endometrioid, two clear cell and one mucinous tumors. Among the comparisons between two groups, SUV_max of the BOT group was significantly lower than that of the MOT group (2.9 ± 1.5 vs. 6.6 ± 2.9, p = 0.0223); otherwise, no significant difference was found in age, CA-125, diameter, or MTV. By receiver-operating characteristic curve analysis, SUV_max of 3.7 was the best cutoff value to differentiate BOTs from stage I MOTs, with a sensitivity of 83.3 % and specificity of 85.7, and the area under curve of 0.893 (p = 0.0001, 95 % CI: 0.601∼0.993).

Conclusions

We demonstrated that SUV_max could distinguish BOTs from stage I MOTs, with a high sensitivity and specificity. Metabolic indices determined by FDG PET/CT were more suitable than volumetric indices for differential diagnosis of the two tumors.     

The value of intratumoral heterogeneity of 18F-FDG uptake to differentiate between primary benign and malignant musculoskeletal tumours on PET/CT

Objective:

The cumulative standardized uptake value (SUV)–volume histogram (CSH) was reported to be a novel way to characterize heterogeneity in intratumoral tracer uptake. This study investigated the value of fluorine-18 fludeoxyglucose (¹⁸F-FDG) intratumoral heterogeneity in comparison with SUV to discriminate between primary benign and malignant musculoskeletal (MS) tumours.

Methods:

The subjects comprised 85 pathologically proven MS tumours. The area under the curve of CSH (AUC-CSH) was used as a heterogeneity index, with lower values corresponding with increased heterogeneity. As 22 tumours were indiscernible on ¹⁸F-FDG positron emission tomography, maximum standardized uptake value (SUV_max), mean standardized uptake value (SUV_mean) and AUC-CSH were obtained in 63 positive tumours. The Mann–Whitney U test and receiver operating characteristic (ROC) analysis were used for analyses.

Results:

The difference between benign (n = 35) and malignant tumours (n = 28) was significant in AUC-CSH (p = 0.004), but not in SUV_max (p = 0.168) and SUV_mean (p = 0.879). The sensitivity, specificity and accuracy for diagnosing malignancy were 61%, 66% and 64% for SUV_max (optical threshold value, >6.9), 54%, 60% and 57% for SUV_mean (optical threshold value, >3) and 61%, 86% and 75% for AUC-CSH (optical threshold value, ≤0.42), respectively. The area under the ROC curve was significantly higher in AUC-CSH (0.71) than SUV_max (0.60) (p = 0.018) and SUV_mean (0.51) (p = 0.005).

Conclusion:

The heterogeneity index, AUC-CSH, has a higher diagnostic accuracy than SUV analysis in differentiating between primary benign and malignant MS tumours, although it is not sufficiently high enough to obviate histological analysis.

Advances in knowledge:

AUC-CSH can assess the heterogeneity of ¹⁸F-FDG uptake in primary benign and malignant MS tumours, with significantly greater heterogeneity associated with malignant MS tumours. AUC-CSH is more diagnostically accurate than SUV analysis in differentiating between benign and malignant MS tumours.     

18F-FDG PET in Patients with Primary Systemic Anaplastic Large Cell Lymphoma: Differential Features According to Expression of Anaplastic Lymphoma Kinase

Purpose

Primary systemic anaplastic large cell lymphoma (ALCL) is divided into two entities according to the expression of anaplastic lymphoma kinase (ALK). We investigated ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) findings in primary systemic ALCL according to ALK expression.

Methods

Thirty-seven patients who had baseline PET before CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone)-based chemotherapy were enrolled. Among them, patients who underwent interim and/or post-therapy PET were further investigated for the treatment response and survival analysis. Baseline PET was analyzed visually and semi-quantitatively using peakSUV, and interim and post-therapy PETs were visually analyzed.

Results

All cases were ¹⁸F-FDG-avid on baseline PET. The peakSUV of ALK-positive ALCL (n = 16, 18.7 ± 10.5) was higher than that of ALK-negative ALCL (n = 21, 10.0 ± 4.9) (P = 0.006). In ALK-negative ALCL, complete response (CR) rate in negative-interim PET was higher than positive-interim PET (100 % vs 37.5 %, P = 0.02); however, there was no such difference in ALK-positive ALCL (100 % vs 75 %, P = 0.19). The 3-year progression-free survival (PFS) was not significantly different between ALK-positive and ALK-negative ALCL (72.7 % vs 47.6 %, P = 0.34). In ALK-negative ALCL, negative interim and post-therapy PET patients had better 3-year PFS than positive interim (83.3 % vs 25.0 %, P = 0.06) and post-therapy PET patients (70.0 % vs 20.0 %, P = 0.04). In contrast, ALK-positive ALCL had no such differences between PFS and PET results.

Conclusions

On baseline PET, all cases showed ¹⁸F-FDG-avidity, and ALK expression was related to higher ¹⁸F-FDG uptake. ALK-positive patients tend to have better PFS than ALK-negative patients. Negative-interim PET was a good indicator of CR, and interim or post-therapy PET was helpful for predicting the prognosis only in the ALK-negative group.     

Prognostic Value of Volume-Based 18F-Fluorodeoxyglucose PET/CT Parameters in Patients with Clinically Node-Negative Oral Tongue Squamous Cell Carcinoma

Objective

To evaluate the prognostic value of volume-based metabolic parameters measured with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) in patients with clinically node-negative (cN0) oral tongue squamous cell carcinoma (OTSCC) as compared with other prognostic factors.

Materials and Methods

In this study, we included a total of 57 patients who had been diagnosed with cN0 tongue cancer by radiologic, ¹⁸F-FDG PET/CT, and physical examinations. The maximum standardized uptake value (SUV_max), average SUV (SUV_avg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for primary tumors were measured with ¹⁸F-FDG PET. The prognostic significances of these parameters and other clinical variables were assessed by Cox proportional hazards regression analysis.

Results

In the univariate analysis, pathological node (pN) stage, American Joint Committee on Cancer (AJCC) stage, SUV_max, SUV_avg, MTV, and TLG were significant predictors for survival. On a multivariate analysis, pN stage (hazard ratio = 10.555, p = 0.049), AJCC stage (hazard ratio = 13.220, p = 0.045), and MTV (hazard ratio = 2.698, p = 0.033) were significant prognostic factors in cN0 OTSCC patients. The patients with MTV ≥ 7.78 cm³ showed a worse prognosis than those with MTV < 7.78 cm³ (p = 0.037).

Conclusion

The MTV of primary tumor as a volumetric parameter of ¹⁸F-FDG PET, in addition to pN stage and AJCC stage, is an independent prognostic factor for survival in cN0 OTSCC.     

Increased Brainstem Serotonergic Transporter Availability in Adult Migraineurs: an [<Superscript>18</Superscript>F]FP-CIT PET Imaging Pilot Study

Purpose

Recent studies have proposed central serotonergic dysfunction as a major pathophysiology of migraine. We investigated serotonin transporter (SERT) availability in migraineurs using F-18-N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ([¹⁸F]FP-CIT) positron emission tomography (PET).

Methods

Brain [¹⁸F]FP-CIT PET images were obtained in eight women with migraine during headache free phase and 12 healthy adult women, 120 min after injection of 185 MBq. Non-displaceable binding potential (BP_ND) of [¹⁸F]FP-CIT, which is an estimate of SERT availability, was calculated at the brainstem and compared with clinical parameters.

Results

BP_ND at the brainstem was significantly higher in adult migraineurs (n = 6, 1.15 ± 0.17) than healthy subjects (0.95 ± 0.14) (p = 0.04). Healthy subjects demonstrated negative correlation between brainstem BP_ND and age (r = −0.64, p = 0.02), whereas this age-related decline pattern was not found in the migraineurs. Severity of migraine attack was significantly correlated with brainstem BP_ND (r = 0.66, p = 0.02), when age and duration of illness were corrected.

Conclusions

Increased SERT availability in the brainstem of adult migraineurs indicates low serotonin neurotransmission during headache-free phase. Patients who experience more painful headaches have lower serotonin neurotransmission. [¹⁸F]FP-CIT PET is a useful in vivo imaging technique for evaluating brainstem SERT availability in migraineurs.     

Prognostic Value of Metabolic Activity Measured by 18F-FDG PET/CT in Patients with Advanced Endometrial Cancer

Purpose

We evaluated the potential prognostic value of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with stage IIIC/IV endometrial cancer.

Methods

Patients with stage IIIC/IV endometrial cancer who had undergone FDG PET/CT workup for staging were enrolled. Maximum standardized uptake values (SUVmax) measured from regions of interest (ROIs) of the primary tumor (SUVt) and lymph nodes (SUVn) were correlated with overall survival (OS). The SUVn was defined as the highest SUVmax of the metastatic lymph nodes. Survival probability was assessed using the Kaplan-Meier method.

Results

A total of 42 patients with a median age of 55.5 years (range 32–76 years) were included. Twenty-nine percent (n = 12) of patients were premenopausal and 71 % (n = 30) were postmenopausal. The average SUVt was 12.9 (range 1.8–36.5), and the average SUVn was 7.3 (range 2.0–22.5). Median follow-up time was 25.9 months (range 1–84 months). Using a SUVt of 9.5 as a cutoff value, two groups with different rates were determined (P = 0.026). In addition, patients with a low SUVn had significantly better OS than those with a high SUVn (P = 0.003). Patients in the International Federation of Obstetrics and Gynecology (FIGO) stage IV group with SUVt ≥ 9.5 or SUVn ≥ 7.3 showed a significantly longer OS than the other groups.

Conclusions

FDG uptake of primary endometrial cancer and lymph nodes might be a prognostic factor in advanced endometrial cancer. More aggressive therapy could be considered in patients with stage IV endometrial cancer and high SUVt and/or high SUVn.     

Prognostic Value of SUVmax Measured by Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography with Computed Tomography in Patients with Gallbladder Cancer

Objective

The aim of this study is to investigate the prognostic value of F-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET)/computed tomography (CT) in gallbladder cancer patients.

Methods

From June 2004 to June 2010, a total of 50 patients with gallbladder cancer who underwent diagnostic staging with F-18 FDG PET/CT following curative or palliative treatments were retrospectively evaluated. For the analysis, all patients were classified by age, sex, maximum standardized uptake value (SUVmax), lymph node (LN) or distant metastasis, serum level of CA19-9 and CEA, type of treatment and American Joint Committee on Cancer (AJCC) stage.

Results

The median survival for the 50 patients was 245 days and the median SUVmax in PET/CT was 8.3 (range, 0-19.7). Patients with SUVmax < 6 survived significantly longer than patients with SUVmax ≥ 6 (median 405 days vs 203 days, p = 0.0400). On Kaplan-Meier analysis, SUVmax (p = 0.0400), stage (p = 0.0001), CA19-9 (p = 0.013), CEA (p = 0.006), LN metastasis (p = 0.0001), distant metastasis (p = 0.0020), type of treatment (p = 0.0001) were significantly associated with overall survival. Multivariate analysis study revealed that the patients with lower SUVmax measured from initial staging PET/CT (p = 0.0380), no LN metastasis (p = 0.0260), a lower stage (p = 0.026) and curative treatment (p = 0.0005) had longer survivals.

Conclusions

The present study shows that SUVmax on F-18 FDG PET/CT can provide prognostic information in patients with gallbladder cancer.     

Radiomics analysis of pre-treatment [<Superscript>18</Superscript>F]FDG PET/CT for patients with metastatic colorectal cancer undergoing palliative systemic treatment

Background

The aim of this study was to assess radiomics features on pre-treatment [¹⁸F]FDG positron emission tomography (PET) as potential biomarkers for response and survival in patients with metastatic colorectal cancer (mCRC).

Methods

Patients with mCRC underwent [¹⁸F]FDG PET/computed tomography (CT) prior to first- or third-line palliative systemic treatment. Tumour lesions were semiautomatically delineated and standard uptake value (SUV), metabolically active tumour volume (MATV), total lesion glycolysis (TLG), entropy, area under the curve of the cumulative SUV-volume histogram (AUC-CSH), compactness and sphericity were obtained.

Results

Lesions of 47 patients receiving third-line systemic treatment had higher SUV_max, SUV_peak, SUV_mean, MATV and TLG, and lower AUC-CSH, compactness and sphericity compared to 52 patients receiving first-line systemic treatment. Therefore, first- and third-line groups were evaluated separately. In the first-line group, anatomical changes on CT correlated negatively with TLG (ρ?=?0.31) and MATV (ρ?=?0.36), and positively with compactness (ρ?=??0.27) and sphericity (ρ?=??0.27). Patients without benefit had higher mean entropy (p?=?0.021). Progression-free survival (PFS) and overall survival (OS) were worse with a decreased mean AUC [hazard ratio (HR) 0.86, HR 0.77] and increase in mean MATV (HR 1.15, HR 1.22), sum MATV (HR 1.14, HR 1.19), mean TLG (HR 1.16, HR 1.22) and sum TLG (HT1.12, HR1.18). In the third-line group, AUC-CSH correlated negatively with anatomical change (ρ?=?0.21). PFS and OS were worse with an increased mean MATV (HR 1.27, HR 1.68), sum MATV (HR 1.35, HR 2.04), mean TLG (HR 1.29, HR 1.52) and sum TLG (HT 1.27, HR 1.80). SUV_max and SUV_peak negatively correlated with OS (HR 1.19, HR 1.21). Cluster analysis of the 10 radiomics features demonstrated no complementary value in identifying aggressively growing lesions or patients with impaired survival.

Conclusion

We demonstrated an association between improved clinical outcome and pre-treatment low tumour volume and heterogeneity as well as high sphericity on [¹⁸F]FDG PET. Future PET imaging research should include radiomics features that incorporate tumour volume and heterogeneity when correlating PET data with clinical outcome.

     

Prognostic Value of Metabolic Tumor Volume Measured by 18F-FDG PET/CT in Locally Advanced Head and Neck Squamous Cell Carcinomas Treated by Surgery

Purpose

We assessed the prognostic value of metabolic tumor volume (MTV) measured using¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) inpatients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Methods

We retrospectively reviewed 56 patients (51 men, five women; mean age 56.0 ± 8.8years) who had locally advanced HNSCC and underwent FDG PET/CT for initial evaluation. All patients had surgical resection and radiotherapy with or without concurrent chemotherapy. The peak standardized uptake value (SUV_peak) and MTV of the target lesion, including primary HNSCC andmetastatic cervical lymph nodes, were measured from FDG PET/CT images. We compared SUV_peak, MTV, and clinicopathologic variables such as age, Eastern Cooperative Oncology Group (ECOG) performance status, pN stage, pT stage, TNM stage, histologic grade and treatment modality to disease-free survival (DFS) and overall survival (OS).

Results

On the initial FDG PET/CT scans, the median SUV_peak was 7.8 (range, 1.8-19.0) and MTV was17.0 cm³ (range, 0.1-131.0 cm³). The estimated 2-year DFS and OS rates were 67.2% and 81.8%. The cutoff points of SUV_peak 6.2 and MTV 20.7 cm³ were the best discriminative values for predicting clinical outcome. MTV and ECOG performance status were significantly related to DFS and OS on univariate and multivariate analyses (p < 0.05).

Conclusion

The MTV obtained from initial FDG PET/CT scan is a significant prognostic factor for disease recurrence and mortality in locally advanced HNSCC treated with surgery and radiotherapy with or without chemotherapy.     

Association Between <Superscript>18</Superscript>F-FDG Avidity and the BRAF Mutation in Papillary Thyroid Carcinoma

Purpose

The BRAF mutation, a potential prognostic factor in papillary thyroid carcinoma (PTC), is associated with a high expression of the glucose transporter gene. We investigated which clinicopathologic factors, including BRAF mutation status, influence ¹⁸F-fluoro-2-deoxyglucose (¹⁸F-FDG) avidity.

Methods

We retrospectively reviewed 55 patients who underwent BRAF analysis from biopsy-confirmed PTC and ¹⁸F-FDG positron emission tomography/computed tomography within 6 months before undergoing thyroid surgery from September 2008 to August 2014. Tumors were considered to be ¹⁸F-FDG avid if the uptake was greater than that of the liver. ¹⁸F-FDG uptake of PTCs was also analyzed semiquantitatively using SUV_max. The association between ¹⁸F-FDG avidity and clinicopathologic variables (age, tumor size, perithyroidal extension, cervical lymph node status, and BRAF mutation status) was investigated.

Results

Twenty-nine (52.7 %) of 55 patients had ¹⁸F-FDG-avid PTCs. PTCs with the BRAF mutation showed higher ¹⁸F-FDG avidity (24/38, 63.2 %) than those without (5/17, 29.4 %). The BRAF mutation (p = 0.025) and tumor size (p = 0.003) were significantly associated with ¹⁸F-FDG avidity in univariate analysis, and the BRAF mutation status remained significant after adjusting for tumor size in multivariate analysis (p = 0.015). In the subgroup of tumor size ≥ 1 cm, the BRAF mutation was the only factor significantly associated with ¹⁸F-FDG avidity (p = 0.021). The mean SUV_max of PTCs with the BRAF mutation was significantly higher than that of those without (4.89 ± 6.12 vs. 1.96 ± 1.10, p = 0.039).

Conclusions

The BRAF mutation must be one of the most important factors influencing ¹⁸F-FDG avidity in PTCs, especially in those with a tumor size ≥ 1 cm.     

FDG PET/CT Response Assessment Criteria for Patients with Hodgkin’s and Non-Hodgkin’s Lymphoma at End of Therapy: A Multiparametric Approach

Purpose

Based on the International Harmonization Project (IHP) criteria, positron emission tomography (PET) response assessment of residual nodal masses in patients with lymphoma after completion of therapy is performed visually using mediastinal blood pool as the reference. The primary objective of this study was to define the optimal reference for PET response assessment. Secondary aim was to assess if morphological criteria on computed tomography (CT) may improve performance of PET.

Methods

This institutional review board approved retrospective study included 137 patients, with Hodgkin’s (n = 43) or non-Hodgkin’s lymphoma (n = 94) assessed for residual masses (n = 180) after completion of therapy with pathology and clinical and imaging surveillance data (mean, 19 months) as the standard of reference. Two readers independently assessed response by IHP and Deauville criteria. The addition of morphological parameters on CT was assessed in relation to therapy response.

Results

Based on the standard of reference, 36 patients (26.3 %) had residual lymphoma. For IHP and Deauville criteria, sensitivity, specificity and accuracy were 97.2 %, 97.2 % (p = 1); 79.2 %, 92.1 % (p < 0.001); and 83.9 %, 93.4 % (p = 0.001), respectively. Of the morphological parameters assessed, only change in size over course of therapy was significant (p < 0.003) and improved specificity for IHP-based interpretation to 90.4 % (p = 0.008).

Conclusions

Using liver as the visual reference to determine PET positivity for lymphoma patients being assessed for residual masses at the end of therapy improves specificity, yet maintains the high sensitivity of PET in identifying residual disease. The addition of change in size after therapy improves specificity of PET when using IHP-based but not Deauville-based interpretation.     

Usefulness of Combined Metabolic–Volumetric Indices of 18F-FDG PET/CT for the Early Prediction of Neoadjuvant Chemotherapy Outcomes in Breast Cancer

Purpose

The purpose of this study was to investigate the usefulness of metabolic-volumetric indices of ¹⁸F- fluorodeoxy-D-glucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) for the evaluation of neoadjuvant chemotherapy outcomes in breast cancer.

Methods

Twenty-four patients with locally advanced breast cancer were enrolled in the study. They underwent baseline ¹⁸F-FDG PET/CT scan and received four or six cycles of neoadjuvant chemotherapy, interim ¹⁸F-FDG PET/CT was done after second cycle of chemotherapy. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary lesions were calculated. Reduction rates of these parameters were obtained between baseline and interim ¹⁸F-FDG PET/CT. Chemotherapy outcomes were assessed using tumor size reduction rate and histological grading system (Miller and Payne system). Reduction rates of SUVmax, MTV, and TLG correlated with chemotherapy outcomes.

Results

MTV and TLG reduction rates showed significant correlation with tumor size reduction rate (R = 0.68, P = 0.0004; R = 0.62, P = 0.002, respectively). However, SUVmax reduction rate showed no significant correlation. MTV and TLG reduction rates were significantly higher in responders than nonresponders, as determined by Miller and Payne system (P < 0.0007, P < 0.002). However, SUVmax reduction rate showed no significant difference. On ROC analysis, the area under the MTV and TLG curves was 0.886, and that of SUVmax was 0.743. Sensitivity, specificity, positive predictive value, and negative predictive value to predict histopathologic response were the same for MTV and TLG, and the values were 100 %, 85.7 %, 83.3 %, and 100 %, respectively (at the reduction rate of 93.2 % for MTV, and 95.8 % for TLG).

Conclusion

Changes of metabolic–volumetric indices successfully reflected the neoadjuvant chemotherapy outcomes. MTV and TLG could be robust indices in discriminating pathologic responder as SUVmax, after neoadjuvant chemotherapy.     

The Role of 18 F-FDG PET/CT in Assessing Therapy Response in Cervix Cancer after Concurrent Chemoradiation Therapy

Purpose

To determine whether persisting cervical fluorodeoxyglucose (FDG) uptake after concurrent chemoradiotherapy (CCRT) for cervical cancer can reflect residual malignancy.

Methods

F-FDG PET/CT was performed before and after CCRT in 136 patients with cervical cancer. The maximum and mean standardized uptake values (SUVmax and SUVmean) were recorded from PET/CT scans performed pre- and post-treatment. SUVs were correlated with treatment response after CCRT. Final treatment response was determined by MRI and further follow-up PET/CT. One hundred four of 136 patients underwent pelvic MRI, and 32 of 136 patients underwent further follow-up PET/CT. Patients were classified into two categories: patients with residual tumor or patients without residual tumor (complete responder). Pre- and post-treatment serum squamous cell carcinoma antigen (SCC) levels were also recorded for comparison. The optimal cutoff value of SUVmax for predicting residual cervical tumor was determined using receiver-operating characteristic (ROC) analysis.

Results

Of 136 patients, 124 showed complete response on further follow-up studies and 12 were confirmed to have residual tumor. The post-treatment SUVmax and pre-/post-treatment SUVmean of complete responders were significantly lower than those of patients with residual tumor: 2.5 ± 0.8 and 7.2 ± 4.2/1.9 ± 0.7 for complete responders and 5.7 ± 2.6 and 12.8 ± 6.9/3.7 ± 0.7 for patients with residual tumor (p < 0.05). The pre-treatment SUVmax and pre-/post-treatment serum SCC levels of the complete responders tended to be lower than those of patients with residual tumor, but this did not have statistical significance. Using ROC analysis, an optimal cutoff SUVmax of 4.0 on the post-treatment PET/CT yielded a sensitivity, specificity, positive predictive value, and negative predictive value of 92 %, 94 %, 61 %, and 99 %, respectively (p < 0.001).

Conclusions

Persistent cervical FDG uptake in¹⁸F-FDG PET/CT after CCRT for cervical cancer may be caused by residual tumor or post-therapy inflammation. A higher cutoff SUVmax than conventional criteria for cervical cancer in post-CCRT PET/CT might help to detect residual tumor.     

Prognostic Significance of Volume-based Metabolic Parameters by 18F-FDG PET/CT in Gallbladder Carcinoma

Purpose

We investigated the prognostic values of volume-based metabolic parameters by ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) in gallbladder carcinoma patients and compared them with other prognostic parameters.

Materials and Methods

We enrolled 44 patients, who were initially diagnosed with gallbladder carcinoma and undergoing ¹⁸F-FDG PET/CT. Various metabolic volume-based PET parameters of primary tumors, including maximum and average standardized uptake values (SUV_max, SUV_avg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), were measured in gallbladder carcinoma patients using mediastinal blood pool activity as a threshold SUV for determining the tumor boundaries. Overall survival analysis was performed using the Kaplan-Meier method with PET parameters and other clinical variables. For determining independent prognostic factors, Cox proportional hazards regression analysis was performed.

Results

Of the 44 enrolled patients, cancer- or treatment-related death occurred in 30 (68.2 %). The mean clinical follow-up period was 22.2 ± 10.4 m (range, 0.6-35.9 m). Univariate analysis demonstrated that clinical or pathologic TNM stage (P < 0.001), treatment modality (P < 0.001), MTV (cutoff = 135 cm³, P = 0.001), and TLG (cutoff = 7,090, P < 0.05) were significant prognostic factors. In multivariate analysis, both clinical or pathologic TNM stage [hazard ratio (HR) = 2.019 (I vs II), 21.287 (I vs III), and 24.354 (I vs IV); P = 0.001) and TLG (HR = 2.930; P < 0.05) were independent prognostic factors for predicting overall survival.

Conclusions

In gallbladder cancer, TLG of the primary tumor, a volume-based metabolic parameter, is a significant independent prognostic factor for overall survival in conjunction with the clinical or pathological TNM stage.     

Correlation between Semi-Quantitative <Superscript>18</Superscript>F-FDG PET/CT Parameters and Ki-67 Expression in Small Cell Lung Cancer

Purpose

The aim of this study was to evaluate the relationship between semiquantitative parameters on ¹⁸F-FDG PET/CT including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) and the expression level of Ki-67 in small-cell lung cancer (SCLC).

Methods

Ninety-four consecutive patients with SCLC were enrolled in this study. They underwent ¹⁸F-FDG PET/CT for initial evaluation of SCLC, and we measured SUVmax, avgSUVmean, MTVsum, and TLGtotal on ¹⁸F-FDG PET/CT images. The protein expression of Ki-67 was examined by immunohistochemical staining.

Results

Significant correlations were found between the MTVsum and Ki-67 labeling index (r = 0.254, p = 0.014) and the TLGtotal and Ki-67 labeling index (r = 0.239, p = 0.020). No correlation was found between the SUVmax and Ki-67 labeling index (r = 0.116, p = 0.264) and the avgSUVmean and Ki-67 labeling index (r = 0.031, p = 0.770). Dividing the Ki-67 expression level into three categories, it was suggested that increasing Ki-67 expression level caused a stepwise increase in the MTVsum and TLGtotal. (p = 0.028 and 0.039, respectively), but not the SUVmax and avgSUVmean (p = 0.526 and 0.729, respectively).

Conclusion

In conclusion, the volume-based parameters of ¹⁸F-FDG PET/CT correlate with immunohistochemical staining of Ki-67 in SCLC. Measurement of the MTVsum and TLGtotal by ¹⁸F-FDG PET/CT might be a simple, noninvasive, and useful method to determine the proliferative potential of cancer cells.     

Prognostic Value of Metabolic Tumor Volume on 11C-Methionine PET in Predicting Progression-Free Survival in High-Grade Glioma

Purpose

C-11 methionine (MET) PET is commonly used for diagnosing high-grade glioma (HGG). Recently, volumetric analysis has been widely applied to oncologic PET imaging. In this study, we investigated the prognostic value of metabolic tumor volume (MTV) on MET PET in HGG.

Methods

A total of 30 patients with anaplastic astrocytoma (n = 12) and glioblastoma multiforme (n = 18) who underwent MET PET before treatment (surgery followed by chemo-radiotherapy) were retrospectively enrolled. Maximal tumor-to-normal brain ratio (TNR_max, maximum tumor activity divided by mean of normal tissue) and MTV (volume of tumor tissue that shows uptake >1.3-fold of mean uptake in normal tissue) were measured on MET PET. Adult patients were classified into two subgroups according to Radiation Therapy Oncology Group Recursive Partitioning Analysis (RTOG RPA) classification. Prognostic values of TNR_max, MTV and clinicopathologic factors were evaluated with regard to progression-free survival (PFS).

Results

Median PFS of all patients was 7.9 months (range 1.0–53.8 months). In univariate analysis, MTV (cutoff 35 cm³) was a significant prognostic factor for PFS (P = 0.01), whereas TNR_max (cutoff 3.3) and RTOG RPA class were not (P = 0.80 and 0.61, respectively). Treatment of surgical resection exhibited a borderline significance (P = 0.06). In multivariate analysis, MTV was the only independent prognostic factor for PFS (P = 0.03).

Conclusion

MTV on MET PET is a significant and independent prognostic factor for PFS in HGG patients, whereas TNR_max is not. Thus, performing volumetric analysis of MET PET is recommended in HGG for better prognostication.     

Evaluation of Bone Metastasis from Hepatocellular Carcinoma Using 18F-FDG PET/CT and 99mTc-HDP Bone Scintigraphy: Characteristics of Soft Tissue Formation

Purpose

Bone metastasis from hepatocellular carcinoma (HCC) can present with soft tissue formation, resulting in oncologic emergency. Contrast-enhanced FDG PET/CT and bone scintigraphy were compared to evaluate characteristics of bone metastases with or without soft tissue formation from HCC.

Methods

Of 4,151 patients with HCC, 263 patients had bone metastases. Eighty-five patients with bone metastasis from HCC underwent contrast-enhanced FDG PET/CT. Fifty-four of the enrolled subjects had recent ^99mTc-HDP bone scintigraphy available for comparison. Metastatic bone lesions were identified with visual inspection on FDG PET/CT, and maximum standardized uptake value (SUV_max) was used for the quantitative analysis. Confirmation of bone metastasis was based on histopathology, combined imaging modalities, or serial follow-up studies.

Results

Forty-seven patients (55%) presented with soft tissue formation, while the remaining 38 patients presented without soft tissue formation. Frequent sites of bone metastases from HCC were the spine (39%), pelvis (19%), and rib cage (14%). The soft-tissue-formation group had more frequent bone pain (77 vs. 37%, p < 0.0001), higher SUV_max (6.02 vs. 3.52, p < 0.007), and higher incidence of photon defect in bone scintigraphy (75 vs. 0%) compared to the non-soft-tissue-formation group. FDG PET/CT had higher detection rate for bone metastasis than bone scintigraphy both in lesion-based analysis (98 vs. 53%, p = 0.0015) and in patient-based analysis (100 vs. 80%, p < 0 .001).

Conclusions

Bone metastasis from HCC showed a high incidence of soft tissue formation requiring emergency treatment. Although the characteristic findings for soft tissue formation such as photon defect in bone scintigraphy are helpful in detection, overall detectability of bone metastasis is higher in FDG PET/CT. Contrast-enhanced PET/CT will be useful in finding and delineating soft-tissue-forming bone metastasis from HCC.