HER2-positive breast cancer: 18F-FDG PET for early prediction of response to trastuzumab plus taxane-based neoadjuvant chemotherapy

Purpose

To investigate the value of ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET/CT) to predict a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

Material and methods

Fifty-seven consecutive women with HER2-positive breast cancer, treated with trastuzumab plus taxane-based NAC, were prospectively included. Maximum Standardized Uptake Value of the primary tumor and axillary nodes were measured at baseline (PET₁.SUV_max) and after the first course of NAC (PET₂.SUV_max). Tumor metabolic volumes were assessed to determine Total Lesion Glycolysis (TLG). The tumor metabolic response (ΔSUV_max and ΔTLG) was calculated.

Results

In univariate analysis, negative hormonal receptor status (p?=?0.04), high tumor grade (p?=?0.03), and low tumor PET ₂ .SUV_max (p?=?0.001) were predictive of pCR. Tumor ΔSUV_max correlated with pCR (p?=?0.03), provided that tumors with low metabolic activity at baseline were excluded. ΔTLG did not correlate with pCR. In multivariate analysis, tumor PET₂.SUV_max?<?2.1 was the best independent predictive factor (Odds ratio =14.3; p?=?0.004) with both negative and positive predictive values of 76 %. Although the metabolic features of the primary tumor did not depend on hormonal receptor status, both the baseline metabolism and early response of axillary nodes were higher if estrogen receptors were not expressed (p?=?0.01 and p?=?0.03, respectively).

Conclusion

In HER2-positive breast cancer, very low tumor residual metabolism after the first cycle of NAC (SUV_max?<?2.1) was the main predictor of pCR. These results should be further explored in multicenter studies and incorporated into the design of clinical trials.     

Evaluation of the PET component of simultaneous [18F]choline PET/MRI in prostate cancer: comparison with [18F]choline PET/CT

Purpose

The aim of this study was to evaluate the positron emission tomography (PET) component of [¹⁸F]choline PET/MRI and compare it with the PET component of [¹⁸F]choline PET/CT in patients with histologically proven prostate cancer and suspected recurrent prostate cancer.

Methods

Thirty-six patients were examined with simultaneous [¹⁸F]choline PET/MRI following combined [¹⁸F]choline PET/CT. Fifty-eight PET-positive lesions in PET/CT and PET/MRI were evaluated by measuring the maximum and mean standardized uptake values (SUV_max and SUV_mean) using volume of interest (VOI) analysis. A scoring system was applied to determine the quality of the PET images of both PET/CT and PET/MRI. Agreement between PET/CT and PET/MRI regarding SUV_max and SUV_mean was tested using Pearson’s product-moment correlation and Bland-Altman analysis.

Results

All PET-positive lesions that were visible on PET/CT were also detectable on PET/MRI. The quality of the PET images was comparable in both groups. Median SUV_max and SUV_mean of all lesions were significantly lower in PET/MRI than in PET/CT (5.2 vs 6.1, p?<?0.05 and 2.0 vs 2.6, p?<?0.001, respectively). Pearson’s product-moment correlation indicated highly significant correlations between SUV_max of PET/CT and PET/MRI (R?=?0.86, p?<?0.001) as well as between SUV_mean of PET/CT and PET/MRI (R?=?0.81, p?<?0.001). Bland-Altman analysis revealed lower and upper limits of agreement of ?2.77 to 3.64 between SUV_max of PET/CT vs PET/MRI and ?1.12 to +2.23 between SUV_mean of PET/CT vs PET/MRI.

Conclusion

PET image quality of PET/MRI was comparable to that of PET/CT. A highly significant correlation between SUV_max and SUV_mean was found. Both SUV_max and SUV_mean were significantly lower in [¹⁸F]choline PET/MRI than in [¹⁸F]choline PET/CT. Differences of SUV_max and SUV_mean might be caused by different techniques of attenuation correction. Furthermore, differences in biodistribution and biokinetics of [¹⁸F]choline between the subsequent examinations and in the respective organ systems have to be taken into account.     

Factors affecting intrapatient liver and mediastinal blood pool 18F-FDG standardized uptake value changes during ABVD chemotherapy in Hodgkin’s lymphoma

Purpose

The aim of our study was to assess the intrapatient variability of 2-deoxy-2-(¹⁸F)-fluoro-D-glucose (¹⁸F-FDG) uptake in the liver and in the mediastinum among patients with Hodgkin’s lymphoma (HL) treated with doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy (CHT).

Methods

The study included 68 patients (30 men, 38 women; mean age 32?±?11 years) with biopsy-proven HL. According to Ann Arbor criteria, 6 were stage I, 34 were stage II, 12 were stage 3 and 16 were stage 4. All of them underwent a baseline (PET0) and an interim (PET2) ¹⁸F-FDG whole-body positron emission tomography (PET)/CT. All patients were treated after PET0 with two ABVD cycles for 2 months that ended 15?±?5 days prior to the PET2 examination. All patients were further evaluated 15?±?6 days after four additional ABVD cycles (PET6). None of the patients presented a serum glucose level higher than 107 mg/dl. The mean and maximum standardized uptake values (SUV) of the liver and mediastinum were calculated using the same standard protocol for PET0, PET2 and PET6, respectively. Data were examined by means of the Wilcoxon matched pairs test and linear regression analysis.

Results

The main results of our study were an increased liver SUV_mean in PET2 (1.76?±?0.35) as compared with that of PET0 (1.57?±?0.31; p?<?0.0001) and PET6 (1.69?±?0.28; p?=?0.0407). The same results were obtained when considering liver SUV_max in PET2 (3.13?±?0.67) as compared with that of PET0 (2.82?±?0.64; p?<?0.0001) and PET6 (2.96?±?0.52; p?=?0.0105). No significant differences were obtained when comparing mediastinum SUV_mean and SUV_max in PET0, PET2 and PET6 (p?>?0.05). Another finding is a relationship in PET0 between liver SUV_mean and SUV_max with the stage, which was lower in those patients with advanced disease (r ²?=?0.1456 and p?=?0.0013 for SUV_mean and r ²?=?0.1277 and p?=?0.0028 for SUV_max).

Conclusion

The results of our study suggest that liver ¹⁸F-FDG uptake is variable in patients with HL during the CHT treatment and the disease course and should be considered carefully when used to define the response to therapy in the interim PET in HL.     

Anatomical and functional volume concordance between FDG PET,and T2 and diffusion-weighted MRI for cervical cancer: a hybrid PET/MR study

Purpose

To evaluate the concordance among ¹⁸F-FDG PET imaging, MR T2-weighted (T2-W) imaging and apparent diffusion coefficient (ADC) maps with diffusion-weighted (DW) imaging in cervical cancer using hybrid whole-body PET/MR.

Methods

This study prospectively included 35 patients with cervical cancer who underwent pretreatment ¹⁸F-FDG PET/MR imaging. ¹⁸F-FDG PET and MR images were fused using standard software. The percent of the maximum standardized uptake values (SUV_max) was used to contour tumours on PET images, and volumes were calculated automatically. Tumour volumes measured on T2-W and DW images were calculated with standard techniques of tumour area multiplied by the slice profile. Parametric statistics were used for data analysis.

Results

FDG PET tumour volumes calculated using SUV_max (14.30?±?4.70) and T2-W imaging volume (33.81?±?27.32 cm³) were similar (P?>?0.05) at 35 % and 40 % of SUV_max (32.91?±?18.90 cm³ and 27.56?±?17.19 cm³ respectively) and significantly correlated (P?<?0.001; r?=?0.735 and 0.766). The mean DW volume was 30.48?±?22.41 cm³. DW volumes were not significantly different from FDG PET volumes at either 35 % SUV_max or 40 % SUV_max or from T2-W imaging volumes (P?>?0.05). PET subvolumes with increasing SUV_max cut-off percentage showed an inverse change in mean ADC values on DW imaging (P?<?0.001, ANOVA).

Conclusion

Hybrid PET/MR showed strong volume concordance between FDG PET, and T2-W and DW imaging in cervical cancer. Cut-off at 35 % or 40 % of SUV_max is recommended for ¹⁸F-FDG PET/MR SUV-based tumour volume estimation. The linear tumour subvolume concordance between FDG PET and DW imaging demonstrates individual regional concordance of metabolic activity and cell density.     

Prognostic value of pretreatment 18F-FDG PET/CT and human papillomavirus type 16 testing in locally advanced oropharyngeal squamous cell carcinoma

Purpose

Human papillomavirus type 16 (HPV-16) positivity is associated with favourable survival in oropharyngeal squamous cell carcinoma (OPSCC). We report here a study of the prognostic significance of ¹⁸F-FDG PET/CT functional parameters and HPV-16 infection in OPSCC patients.

Methods

We retrospectively analysed 60 patients with stage III or IV OPSCC who had had a pretherapy ¹⁸F-FDG PET/CT scan and had completed concurrent chemoradiotherapy (n?=?58) or curative radiotherapy (n?=?2). All patients were followed up for ≥24?months or until death. We determined total lesion glycolysis (TLG) and the maximal standardized uptake values (SUV_max) of the primary tumour and neck lymph nodes from the pretherapy ¹⁸F-FDG PET/CT scan. Optimal cut-offs of the ¹⁸F-FDG PET/CT parameters were obtained by receiver operating characteristic (ROC) curve analyses. Pretherapy tumour biopsies were studied by polymerase chain reaction to determine HPV infection status.

Results

The pretherapy tumour biopsies were positive for HPV-16 in 12 patients (20.0?%). Cox regression analyses revealed HPV-16 positivity and tumour TLG >135.3?g to be independently associated with overall survival (p?=?0.027 and 0.011, respectively). However, only tumour TLG >135.3?g was independently associated with progression-free survival, disease-free survival and locoregional control (p?=?0.011, 0.001 and 0.034, respectively). A scoring system was formulated to define distinct overall survival groups using tumour TLG and HPV-16 status. Patients positive for HPV-16 and with tumour TLG ≤135.3?g experienced better survival than those with tumour TLG >135.3?g and no HPV infection (p?=?0.001).

Conclusion

Tumour TLG was an independent predictor of survival in patients with locally advanced OPSCC. A scoring system was developed and may serve as a risk stratification strategy for guiding therapy.     

Prognostic value of metabolic tumor burden on 18F-FDG PET in nonsurgical patients with non-small cell lung cancer

Purpose

The objective of this study was to assess the prognostic value of metabolic tumor burden on 2-deoxy-2-[¹⁸F]fluoro-D-glucose (¹⁸F-FDG) positron emission tomography (PET)/CT measured with metabolic tumor volume (MTV) and total lesion glycolysis (TLG), independent of Union Internationale Contra la Cancrum (UICC)/American Joint Committee on Cancer (AJCC) tumor, node, and metastasis (TNM) stage, in comparison with that of standardized uptake value (SUV) in nonsurgical patients with non-small cell lung cancer (NSCLC).

Methods

This study retrospectively reviewed 169 consecutive nonsurgical patients (78 men, 91 women, median age of 68?years) with newly diagnosed NSCLC who had pretreatment ¹⁸F-FDG PET/CT scans. The ¹⁸F-FDG PET/CT scans were performed in accordance with National Cancer Institute guidelines. The MTV of whole-body tumor (MTV_WB), of primary tumor (MTV_T), of nodal metastases (MTV_N), and of distant metastases (MTV_M); the TLG of whole-body tumor (TLG_WB), of primary tumor (TLG_T), of nodal metastases (TLG_N), and of distant metastases (TLG_M); the SUV_max of whole-body tumor (SUV_maxWB), of primary tumor (SUV_maxT), of nodal metastases (SUV_maxN), and of distant metastases (SUV_maxM) as well as the SUV_mean of whole-body tumor (SUV_meanWB), of primary tumor (SUV_meanT), of nodal metastases (SUV_meanN), and of distant metastases (SUV_meanM) were measured with the PETedge tool on a MIMvista workstation with manual adjustment. The median follow-up among survivors was 35?months from the PET/CT (range 2?C82?months). Statistical methods included Kaplan-Meier curves, Cox regression, and C-statistics.

Results

There were a total of 139 deaths during follow-up. Median overall survival (OS) was 10.9?months [95% confidence interval (CI) 9.0?C13.2?months]. The MTV was statistically associated with OS. The hazard ratios (HR) for 1 unit increase of ln(MTV_WB), ??(MTV_T), ??(MTV_N), and ??(MTV_M) before/after adjusting for stage were: 1.47/1.43 (p?p?p?p?=?0.007/0.043), respectively. TLG had statistically significant associations with OS with the HRs for 1 unit increase in ln(TLG_WB), ??(TLG_T), ??(TLG_N), and ??(TLG_M) before/after adjusting for stage being 1.36/1.33 (p?p?=?0.001/0.002), 1.05/1.04 (p?p?=?0.003/0.024), respectively. The ln(SUV_maxWB) and ??(SUV_maxN) were statistically associated with OS with the corresponding HRs for a 1 unit increase before/after adjusting for stage being 1.46/1.43 (p?=?0.013/0.024) and 1.22/1.16 (p?=?0.002/0.040). The ??(SUV_meanN) was statistically associated with OS before and after adjusting for stage with HRs for a 1 unit increase of 1.32 (p?p?=?0.015), respectively. The ??(SUV_meanM) and ??(SUV_maxM) were statistically associated with OS before adjusting for stage with HRs for a 1 unit increase of 1.26 (p?=?0.017) and 1.18 (p?=?0.007), respectively, but not after adjusting for stage (p?=?0.127 and 0.056). There was no statistically significant association between OS and ??(SUV_maxT), ln(SUV_meanWB), or ??(SUV_meanT). There was low interobserver variability among three radiologists with intraclass correlation coefficients (ICC) greater than 0.94 for SUV_maxWB, ln(MTV_WB), and ln(TLG_WB). Interobserver variability was higher for SUV_meanWB with an ICC of 0.806.

Conclusion

Baseline metabolic tumor burdens at the level of whole-body tumor, primary tumor, nodal metastasis, and distant metastasis as measured with MTV and TLG on FDG PET are prognostic measures independent of clinical stage with low inter-observer variability and may be used to further stratify nonsurgical patients with NSCLC. This study also suggests MTV and TLG are better prognostic measures than SUV_max and SUV_mean. These results will need to be validated in larger cohorts in a prospective study.     

Metabolic parameters using 18F-FDG PET/CT correlate with occult lymph node metastasis in squamous cell lung carcinoma

Purpose

The aim of this study was to investigate predictability of occult lymph node metastasis (OLM) using metabolic parameters on pretreatment ¹⁸F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/CT in squamous cell non-small cell lung carcinoma (SC-NSCLC) patients who were clinically node negative (cN0) before surgery.

Methods

A total of 63 cN0 SC-NSCLC patients (M/F = 61/2, mean age 64.1?±?8.0) who underwent curative surgery with lymph node dissection were enrolled in this study. Metabolic tumor volume (MTV) of the primary tumor was obtained with a standardized uptake value (SUV) threshold of 2.5. Total lesion glycolysis (TLG) was calculated by multiplication of the MTV and its SUV_mean. Metabolic parameters (SUV_max, MTV, and TLG) and clinicopathological factors were analyzed for OLM.

Results

Of 63 patients, 12 (19.0 %) had OLM. Significantly higher SUV_max, MTV, TLG, and pathological tumor size were observed in patients with OLM. The optimal cutoff values for prediction of OLM determined using a receiver-operating characteristic (ROC) curve were 8.8 for SUV_max, 18.9 cm³ for MTV, 88.4 for TLG, and 2.8 cm for pathological tumor size. Univariate analysis showed correlation of SUV_max, MTV, and TLG with the rate of OLM. In multivariate analyses, high SUV_max and MTV showed an association with an increased risk of OLM, after adjusting for age, sex, pathological tumor size, T stage, and location.

Conclusion

Metabolic parameters on pretreatment ¹⁸F-FDG PET/CT were significant predictors for OLM in cN0 SC-NSCLC patients. Surgical planning can be tailored based on the parameters in order to reduce the risk of hidden residual lymph node metastases in patients.     

Comparison of lesion detection and quantitation of tracer uptake between PET from a simultaneously acquiring whole-body PET/MR hybrid scanner and PET from PET/CT

Purpose

PET/MR hybrid scanners have recently been introduced, but not yet validated. The aim of this study was to compare the PET components of a PET/CT hybrid system and of a simultaneous whole-body PET/MR hybrid system with regard to reproducibility of lesion detection and quantitation of tracer uptake.

Methods

A total of 46 patients underwent a whole-body PET/CT scan 1?h after injection and an average of 88?min later a second scan using a hybrid PET/MR system. The radioactive tracers used were ¹⁸F-deoxyglucose (FDG), ¹⁸F-ethylcholine (FEC) and ⁶⁸Ga-DOTATATE (Ga-DOTATATE). The PET images from PET/CT (PET_CT) and from PET/MR (PET_MR) were analysed for tracer-positive lesions. Regional tracer uptake in these foci was quantified using volumes of interest, and maximal and average standardized uptake values (SUV_max and SUV_avg, respectively) were calculated.

Results

Of the 46 patients, 43 were eligible for comparison and statistical analysis. All lesions except one identified by PET_CT were identified by PET_MR (99.2?%). In 38 patients (88.4?%), the same number of foci were identified by PET_CT and by PET_MR. In four patients, more lesions were identified by PET_MR than by PET_CT, in one patient PET_CT revealed an additional focus compared to PET_MR. The mean SUV_max and SUV_avg of all lesions determined by PET_MR were by 21?% and 11?% lower, respectively, than the values determined by PET_CT (p?<?0.05), and a strong correlation between these variables was identified (Spearman rho 0.835; p?<?0.01).

Conclusion

PET/MR showed equivalent performance in terms of qualitative lesion detection to PET/CT. The differences demonstrated in quantitation of tracer uptake between PET_CT and PET_MR were minor, but statistically significant. Nevertheless, a more detailed study of the quantitative accuracy of PET_MR and the factors governing it is needed to ultimately assess its accuracy in measuring tissue tracer concentrations.     

Pretreatment tumor SUV<Subscript>max</Subscript> predicts disease-specific and overall survival in patients with head and neck soft tissue sarcoma

Purpose

Head and neck soft tissue sarcoma (HNSTS) is a rare type of tumor with various histological presentations and clinical behaviors. ¹⁸F-FDG PET/CT is being increasingly used for staging, grading, and predicting treatment outcomes in various types of human cancers, although this modality has been rarely studied in the survival prediction of HNSTS. Here we examined the prognostic value of tumor metabolic parameters measured using ¹⁸F-FDG PET/CT in patients with HNSTS.

Methods

This study included 36 consecutive patients with HNSTS who underwent ¹⁸F-FDG PET/CT scanning prior to treatment at our institution. Tumor gross total volume (GTV) was measured from pretreatment contrast-enhanced CT scans, and maximum standardized uptake value (SUV_max), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured using pretreatment ¹⁸F-FDG PET/CT scans. Univariate and multivariate Cox proportional hazard regression analyses were used to identify associations between imaging parameters and disease-specific survival (DSS) or overall survival (OS).

Results

Univariate analyses showed that SUV_max, MTV, and TLG, but not GTV, were significantly associated with DSS and OS (all P?<?0.05). After controlling for clinicopathological factors, SUV_max, MTV, and TLG were significantly associated with DSS and OS (all P?<?0.05). Patients with a tumor SUV_max value of >7.0 experienced an approximately fivefold increase in mortality in terms of DSS and OS relative to those with a tumor SUV_max <7.0.

Conclusion

Quantitative metabolic measurements on pretreatment ¹⁸F-FDG PET/CT can yield values that are significantly predictive of survival after treatment for HNSTS.

     

Prognostic Value of Tumor-to-Blood Standardized Uptake Ratio in Patients with Resectable Non-Small-Cell Lung Cancer

Objectives

Previously published studies showed that the standard tumor-to-blood standardized uptake value (SUV) ratio (SUR) was a more accurate prognostic method than tumor maximum standardized uptake value (SUV_max). This study evaluated and compared prognostic value of positron emission tomography (PET) parameters and normalized value of PET parameters by blood pool SUV in non-small-cell lung cancer (NSCLC) patients who received curative surgery.

Methods

Seventy-seven patients who underwent curative resection for NSCLC between January 2010 to December 2013 were enrolled in this study. ¹⁸Fluorine-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) was performed before surgery. The mean standardized uptake value (SUV_mean), SUV_max, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of each lesion was measured, on the workstation. SUR_mean, SUR_max, and TLGSUR were calculated by dividing each of them by descending aorta SUV_mean. Cox proportional hazards regression was used to analyze the effect of age, sex, pathological parameters, and PET parameters on recurrence and death.

Results

In Cox regression analysis, N stage predicted for both recurrence (p?<?0.0001) and death (p?<?0.0001). SUR_max predicted recurrence (p?=?0.0014), not death. Area under the receiver operating characteristic curve of SUR_max was 0.759 with cutoff value 4.004. However, SUV_max, SUV_mean, MTV, TLG, SUR_mean, and TLGSUR predicted neither recurrence nor death.

Conclusions

Among PET parameters, SUR_max was the independent predictor of recurrence in NSCLC patients who received curative surgery. N stage was the independent prognostic factor for both recurrence and death. Both parameters could be used to stratify the risk of NSCLC patients.

     

Prognostic significance of preoperative metabolic tumour volume and total lesion glycolysis measured by 18F-FDG PET/CT in squamous cell carcinoma of the oral cavity

Purpose

Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from ¹⁸F-FDG PET/CT are emerging prognostic biomarkers in human solid cancers; yet few studies have investigated their clinical and prognostic significance in oral cavity squamous cell carcinoma (OSCC). The present retrospective study evaluated the utility of pretreatment MTV and TLG measured by ¹⁸F-FDG PET/CT to predict survival and occult metastasis (OM) in OSCC.

Methods

Of 162 patients with OSCC evaluated preoperatively by ¹⁸F-FDG PET/CT, 105 who underwent definitive surgery with or without adjuvant therapy were eligible. Maximum standardized uptake value (SUV_max), MTV and TLG were measured. For calculation of MTV, 3-D regions of interest were drawn and a SUV threshold of 2.5 was used for defining regions. Univariate and multivariate analyses identified clinicopathological and imaging variables associated with OM, disease-free survival (DFS) and overall survival (OS).

Results

The median (range) SUV_max, MTV and TLG were 7.3 (0.7–41.9), 4.5 ml (0.7–115.1 ml) and 18.3 g (2.4–224.1 g), respectively. Of 53 patients with clinically negative lymph nodes, OM was detected in 19 (36 %). By univariate and multivariate analyses, MTV (P?=?0.018) and TLG (P?=?0.011) were both independent predictive factors for OM, although they were not independent of each other. The 4-year DFS and OS rates were 53.0 % and 62.0 %, respectively. Univariate and multivariate analyses revealed that MTV (P?=?0.001) and TLG (P?=?0.006), with different cut-off levels, were both independent predictive factors for DFS, although they were not independent of each other, and MTV (P?=?0.001), TLG (P?=?0.002) and the involved resection margin (P?=?0.007) were independent predictive factors for OS.

Conclusion

Pretreatment MTV and TLG may be useful in stratifying the likelihood of survival and predicting OM in OSCC.     

Predictive value of pre-therapy 18F-FDG PET/CT for the outcome of 18F-FDG PET-guided radiotherapy in patients with head and neck cancer

Purpose

The aim of this study was to evaluate the predictive role of pre-therapy fluorodeoxyglucose (FDG) uptake parameters of primary tumour in head and neck cancer (HNC) patients undergoing intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) on FDG-positive volume—positron emission tomography (PET) gross tumour volume (PET-GTV).

Methods

This retrospective study included 19 patients (15 men and 4 women, mean age 59.2 years, range 23–81 years) diagnosed with HNC between 2005 and 2011. Of 19 patients, 15 (79 %) had stage III–IV. All patients underwent FDG PET/CT before treatment. Metabolic indexes of primary tumour, including metabolic tumour volume (MTV), maximum and mean standardized uptake value (SUV_max, SUV_mean) and total lesion glycolysis (TLG) were considered. Partial volume effect correction (PVC) was performed for SUV_mean and TLG estimation. Correlations between PET/CT parameters and 2-year disease-free survival (DFS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) were assessed. Median patient follow-up was 19.2 months (range 4–24 months).

Results

MTV, TLG and PVC-TLG predicting patients’ outcome with respect to all the considered local and distant disease control endpoints (LRFS, DMFS and DFS) were 32.4 cc, 469.8 g and 547.3 g, respectively. SUV_mean and PVC-SUV_mean cut-off values predictive of LRFS and DFS were 10.8 and 13.3, respectively. PVC was able to compensate errors up to 25 % in the primary HNC tumour uptake. Moreover, PVC enhanced the statistical significance of the results.

Conclusion

FDG PET/CT uptake parameters are predictors of patients’ outcome and can potentially identify patients with higher risk of treatment failure that could benefit from more aggressive approaches. Application of PVC is recommended for accurate measurement of PET parameters.     

The value of <Superscript>18</Superscript>F-FDG PET before and after induction chemotherapy for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy in oesophageal adenocarcinoma

Purpose

The purpose of our study was to determine the value of ¹⁸F-FDG PET before and after induction chemotherapy in patients with oesophageal adenocarcinoma for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy (CRT).

Methods

In 70 consecutive patients receiving a three-step treatment strategy of induction chemotherapy and preoperative chemoradiotherapy for oesophageal adenocarcinoma, ¹⁸F-FDG PET scans were performed before and after induction chemotherapy (before preoperative CRT). SUV_max, SUV_mean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were determined at these two time points. The predictive potential of (the change in) these parameters for a poor pathologic response, progression-free survival (PFS) and overall survival (OS) was assessed.

Results

A poor pathologic response after induction chemotherapy and preoperative CRT was found in 27 patients (39 %). Patients with a poor pathologic response experienced less of a reduction in TLG after induction chemotherapy (p?<?0.01). The change in TLG was predictive for a poor pathologic response at a threshold of ?26 % (sensitivity 67 %, specificity 84 %, accuracy 77 %, PPV 72 %, NPV 80 %), yielding an area-under-the-curve of 0.74 in ROC analysis. Also, patients with a decrease in TLG lower than 26 % had a significantly worse PFS (p?=?0.02), but not OS (p?=?0.18).

Conclusions

¹⁸F-FDG PET appears useful to predict a poor pathologic response as well as PFS early after induction chemotherapy in patients with oesophageal adenocarcinoma undergoing a three-step treatment strategy. As such, the early ¹⁸F-FDG PET response after induction chemotherapy could aid in individualizing treatment by modification or withdrawal of subsequent preoperative CRT in poor responders.

     

Combined pre-treatment MRI and 18F-FDG PET/CT parameters as prognostic biomarkers in patients with cervical cancer

Objective

To determine the associations of quantitative parameters derived from multiphase contrast-enhanced magnetic resonance imaging (CE-MRI), diffusion-weighted (DW) MRI and 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT) with clinico-histopathological prognostic factors, disease-free survival (DFS) and overall survival (OS) in patients with cervical cancer.

Methods and materials

Our institutional review board approved this retrospective study of 49 patients (median age, 45 years) with histopathologically proven IB-IVB International Federation of Gynecology and Obstetrics (FIGO) cervical cancer who underwent pre-treatment pelvic MRI and whole-body 18F-FDG PET/CT between February 2009 and May 2012. Maximum diameter (_maxTD), percentage enhancement (PE) and mean apparent diffusion coefficient (ADC_mean) of the primary tumor were measured on MRI. Maximum standardized uptake value (SUV_max), metabolic tumor volume (MTV), total lesion glycolysis (TLG) were measured on 18F-FDG PET/CT. Correlations between imaging metrics and clinico-histopathological parameters including revised 2009 FIGO stage, tumor histology, grade and lymph node (LN) metastasis at diagnosis were evaluated using the Wilcoxon rank sum test. Cox modeling was used to determine associations with DFS and OS.

Results

Median follow-up was 17 months. 41 patients (83.6%) were alive. 8 patients (16.3%) died of disease. Progression/recurrence occurred in 17 patients (34.6%). Significant differences were observed in ADC_mean, SUV_max, MTV and TLG according to FIGO stage (p < 0.001–0.025). There were significant correlations between ADC_mean, MTV, TLG and LN metastasis (p = 0.017–0.032). SUV_max was not associated with LN metastasis. FIGO stage (p = 0.017/0.033), LN metastases (p = 0.001/0.020), ADC_mean (p = 0.007/0.020) and MTV (p = 0.014/0.026) were adverse predictors of both DFS/OS. _maxTD (p = 0.005) and TLG (p = 0.024) were adverse predictors of DFS. PE and SUV_max did not correlate with DFS or OS (p = 0.18–0.72).

Conclusions

Quantitative parameters derived from pre-treatment DW-MRI (ADC_mean) and from 18F-FDG PET/CT (MTV and TLG) were associated with high-risk features and may serve as prognostic biomarkers of survival in patients with cervical cancer.     

Role of 18F-FDG PET/CT in the prediction of gastric cancer recurrence after curative surgical resection

Purpose

The study evaluated the role of preoperative ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in the prediction of recurrent gastric cancer after curative surgical resection.

Methods

A total of 271 patients with gastric cancer who underwent ¹⁸F-FDG PET/CT and subsequent curative surgical resection were enrolled. All patients underwent follow-up for cancer recurrence with a mean duration of 24?±?12?months. ¹⁸F-FDG PET/CT images were visually assessed and, in patients with positive ¹⁸F-FDG cancer uptake, the maximum standardized uptake value (SUV_max) of cancer lesions was measured. ¹⁸F-FDG PET/CT findings were tested as prognostic factors for cancer recurrence and compared with conventional prognostic factors. Furthermore, ¹⁸F-FDG PET/CT findings were assessed as prognostic factors according to histopathological subtypes.

Results

Of 271 patients, 47 (17?%) had a recurrent event. Positive ¹⁸F-FDG cancer uptake was shown in 149 patients (55?%). Tumour size, depth of invasion, presence of lymph node metastasis, positive ¹⁸F-FDG uptake and SUV_max were significantly associated with tumour recurrence in univariate analysis, while only depth of invasion, positive ¹⁸F-FDG uptake and SUV_max had significance in multivariate analysis. The 24-month recurrence-free survival rate was significantly higher in patients with negative ¹⁸F-FDG uptake (95?%) than in those with positive ¹⁸F-FDG uptake (74?%; p?18F-FDG uptake was a significant prognostic factor in patients with tubular adenocarcinoma (p?=?0.003) or poorly differentiated adenocarcinoma (p?=?0.0001). However, only marginal significance was shown in patients with signet-ring cell carcinoma and mucinous carcinoma (p?=?0.05).

Conclusion

¹⁸F-FDG uptake of gastric cancer is an independent and significant prognostic factor for tumour recurrence. ¹⁸F-FDG PET/CT could provide effective information on the prognosis after surgical resection of gastric cancer, especially in tubular adenocarcinoma and poorly differentiated adenocarcinoma.     

The role of metabolic tumor volume and total lesion glycolysis on 18F-FDG PET/CT in the prognosis of epithelial ovarian cancer

Purpose

This study assessed the prognostic value of pre-operative 2-[¹⁸F] fluoro-2-deoxy-D-glucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) volumetric parameters, including metabolic tumor volume (MTV) and total lesion glycolysis (TLG), in patients with epithelial ovarian cancer.

Methods

A total of 175 patients with epithelial ovarian cancer who underwent ¹⁸?F-FDG PET/CT and subsequent cytoreductive surgery were retrospectively enrolled. Maximum standardized uptake value (SUVmax) on ¹⁸F-FDG PET/CT was measured for all patients. Because nine patients showed low tumor-to-background uptake ratios, MTV and TLG were measured in 166 patients. Univariate and multivariate analyses were performed to evaluate the prognostic significance of SUVmax, MTV, TLG, and clinicopathological factors for disease progression-free survival.

Results

Disease progressed in 78 (44.6 %) of the 175 patients, and the 2-year disease progression-free survival rate was 57.5 %. Univariate analysis showed that tumor stage, histopathological type, presence of regional lymph node metastasis, residual tumor after cytoreductive surgery, pre-operative serum carbohydrate antigen 125 (CA125) level, SUVmax, MTV, and TLG were significant prognostic factors (p?100.0).

Conclusion

Along with tumor stage, TLG is an independent prognostic factor for disease progression after cytoreductive surgery in patients with epithelial ovarian cancer. By combining tumor stage and TLG, one can further stratify the risk of disease progression for patients undergoing cytoreductive surgery.     

A pilot study on lung cancer detection based on regional metabolic activity distribution in digital low-dose 18F-FDG PET

ObjectivesTo investigate the potential of automatic lung cancer detection on submillisievert dose ¹⁸F-fludeoxyglucose (¹⁸F-FDG) scans using different positron emission tomography (PET) parameters, as a primary step towards a potential new indication for ¹⁸F-FDG PET in lung cancer screening.MethodsWe performed a retrospective cohort analysis with 83 patients referred for ¹⁸F-FDG PET/CT, including of 34 patients with histology-proven lung cancer and 49 patients without lung disease. Aside clinical standard PET images (PET_100%) two additional low-dose PET reconstructions were generated, using only 15 s and 5 s of the 150 s list mode raw data of the full-dose PET, corresponding to 10% and 3.3% of the original ¹⁸F-FDG activity. The lungs were subdivided into three segments on each side, and each segment was classified as normal or containing cancer. The following standardized uptake values (SUVs) were extracted from PET per lung segment: SUV_mean, SUV_hot5, SUV_median, SUV_std and SUV_total. A multivariate linear regression model was used and cross-validated. The accuracy for lung cancer detection was tested with receiver operating characteristics analysis and T-statistics was used to calculate the weight of each parameter.ResultsThe T-statistics showed that SUV_std was the most important discriminative factor for lung cancer detection. The multivariate model achieved an area under the curve of 0.97 for full-dose PET, 0.85 for PET_10% with PET_3.3% reconstructions resulting in a still high sensitivity the PET_10% reconstruction of 80%.ConclusionThis pilot study indicates that segment-based, quantitative PET parameters of low-dose PET reconstructions could be used to automatically detect lung cancer with high sensitivity.Advances in knowledgeAutomated assessment of PET parameters in low-dose PET may aid for an early detection of lung cancer.     

Pretreatment quantitative 18F-FDG PET/CT parameters as a predictor of survival in adenoid cystic carcinoma of the salivary glands

PurposeThe aim of this study was to determine the unique prognostic value of quantitative ¹⁸F-FDG PET/CT parameters to assess progression-free survival (PFS), distant metastasis-free survival (DMFS), and overall survival (OS) in patients with salivary gland adenoid cystic carcinoma (ACC).MethodsWe performed a retrospective study including 23 patients (15 men, 8 women; median age, 58 years; range, 21–91 years) with salivary gland ACC between January 2009 and October 2017 who underwent ¹⁸F-FDG PET/CT scan prior to treatment. Maximum, mean, peak, tumor-to-mediastinal blood pool and tumor-to-liver standardized uptake values (SUV_max, SUV_mean, SUV_peak, SUV_ratio[med] and SUV_ratio[liver]), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were obtained from ¹⁸F-FDG PET/CT. The prognostic value of quantitative ¹⁸F-FDG PET/CT parameters and other clinicopathological variables were evaluated utilizing the Cox proportional regression analysis.ResultsThe 3-year and 5-year OS for all the patients were 90.9%, and 62.3%, respectively. Log rank test determined that the SUV_ratio[med], SUV_ratio[liver], MTV and TLG were predictive factors of DMFS, PFS, and OS (p < 0.05), furthermore, SUV_max, minor salivary gland tumors and DM at initial diagnosis (M1 stage) were predictor for PFS; M1 stage and overall stage 3–4 predicted DMFS (all p < 0.05). Cox regression analyses confirmed that the higher SUV_ratio[med], SUV_ratio[liver], MTV, and TLG values predicted DMFS, PFS and OS independently, whereas SUV_max was an independent predictor of only PFS (p < 0.05).ConclusionsThe pretreatment metabolic ¹⁸F-FDG PET/CT parameters may reflect tumor aggressiveness in patients with salivary gland ACC and may potentially be utilized as a prognostic biomarker.     

FDG PET/CT in Crohn’s disease: correlation of quantitative FDG PET/CT parameters with clinical and endoscopic surrogate markers of disease activity

Purpose

The aim of this study was to determine the feasibility and potential clinical utility of assessment of Crohn’s disease (CD) activity by ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT employing a new quantitative approach.

Methods

A total of 22 subjects (mean age 37) with CD who had undergone FDG PET/CT followed by ileocolonoscopy within 1 week were included in this analysis. The CD endoscopy index of severity (CDEIS) for various bowel segments was calculated. The CD activity index (CDAI) was evaluated, and fecal calprotectin was measured. On PET, regions with increased FDG uptake in large bowel were segmented with an adaptive contrast-oriented thresholding algorithm, and metabolically active volume (MAV), uncorrected mean standardized uptake value (SUV_mean), partial volume-corrected SUV_mean (PVC-SUV_mean), SUV_max, uncorrected total lesion glycolysis (TLG = MAV × SUV_mean), and PVC total lesion glycolysis (PVC-TLG = MAV × PVC-SUV_mean) were measured. Global CD activity score (GCDAS) was calculated as the sum of PVC-TLG over all clinically significant FDG-avid regions in each subject. Correlations between regional PET quantification measures (SUVs, TLGs) and CDEIS were calculated. Correlations between the global PET quantification measure (GCDAS, global SUVs) with CDAI, fecal calprotectin, CDEIS, and CRP level were also calculated.

Results

SUV_max, PVC-SUV_mean, and PVC-TLG significantly correlated with segment CDEIS subscores (r?=?0.50, r?=?0.69, and r?=?0.31, respectively; p?<?0.05). GCDAS significantly correlated with CDAI and fecal calprotectin (r?=?0.64 and r?=?0.51, respectively; p?<?0.05).

Conclusion

By employing this new quantitative approach, we were able to calculate indices of regional and global CD activity, which correlated well with both clinical and pathological disease activity surrogate markers. This approach may be of clinical importance in measuring both global disease activity and treatment response in patients with CD.     

PET/CT studies of multiple myeloma using 18 F-FDG and 18 F-NaF: comparison of distribution patterns and tracers’ pharmacokinetics

Objective

The aim of this prospective study is to evaluate the combined use of fluorine-18 fluorodeoxyglucose (¹⁸?F-FDG) and fluorine-18 sodium fluoride (¹⁸?F-NaF) PET/CT in the skeletal assessment of patients with multiple myeloma (MM) and to compare the efficacy of these two PET tracers regarding detection of myeloma-indicative osseous lesions.

Patients and methods

The study includes 60 patients with multiple myeloma (MM) diagnosed according to standard criteria. All patients underwent dynamic (dPET/CT) scanning of the pelvis as well as whole body PET/CT studies with both tracers. The interval between the two exams was one day. Sites of focal increased ¹⁸?F-FDG uptake were considered as highly suspicious of myelomatous involvement. The lesions detected on the ¹⁸?F-NaF PET/CT scans were then correlated with those detected on ¹⁸?F-FDG PET/CT, which served as a reference. Moreover, the ¹⁸?F-FDG PET/CT results were also correlated with the low-dose CT findings. The evaluation of dPET/CT studies was based on qualitative evaluation, SUV calculation, and quantitative analysis based on a 2-tissue compartment model and a non-compartmental approach.

Results

Whole body ¹⁸?F-FDG PET/CT revealed approximately 343 focal lesions while ¹⁸?F-NaF PET/CT revealed 135 MM-indicative lesions (39 % correlation). CT demonstrated 150 lesions that correlated with those in ¹⁸?F-FDG PET/CT (44 % correlation). Six patients demonstrated a diffuse pattern of disease with ¹⁸?F-FDG, while 15 of them had a mixed (diffuse and focal) pattern of skeletal ¹⁸?F-FDG uptake. A high number of degenerative, traumatic and arthritic disease lesions were detected with ¹⁸?F-NaF PET/CT. In three patients with multiple focal ¹⁸?F-FDG-uptake, ¹⁸?F-NaF PET/CT failed to demonstrate any bone lesion. The dPET/CT scanning of the pelvic area with ¹⁸?F-FDG and ¹⁸?F-NaF revealed 77 and 24 MM-indicative lesions, respectively. Kinetic analysis of ¹⁸?F-FDG revealed the following mean values: SUV_aver?=?5.1, k₁?=?0.37 (1/min), k₃?=?0.10 (1/min), V_B?=?0.06, influx?=?0.04 (1/min), FD?=?1.28; the respective values for ¹⁸?F-NaF were SUV_average?=?10.7, k₁?=?0.25 (1/min), k₃?=?0.34 (1/min), V_B?=?0.02, influx?=?0.10 (1/min), FD?=?1.37. Apart from the correlation between V_B of ¹⁸?F-FDG and k₁ of ¹⁸?F-NaF (r?=?0.54), no other significant correlation was observed between the two tracers’ kinetic parameters. We found a significant correlation between FD and SUV_average (r?=?0.93), FD and SUV_max (r?=?0.80), FD and influx ( r?=?0.85), as well as between influx and SUV_average (r?=?0.74) for ¹⁸?F-FDG. In ¹⁸?F-NaF we observed the most significant correlations between FD and SUV_average (r?=?0.97), FD and SUV_max (r?=?0.87), and between influx and k₁ (r?=?0.72).

Conclusion

The combined use of ¹⁸?F-FDG PET/CT and ¹⁸?F-NaF PET/CT provides different molecular information regarding the biological processes that take place in a MM osseous lesion. ¹⁸?F-FDG PET/CT proved to be a more specific biomarker than ¹⁸?F-NaF PET/CT in multiple myeloma skeletal assessment.