The role of FDG PET/CT in patients treated with neoadjuvant chemotherapy for localized bone sarcomas

Purpose

The histological response to neoadjuvant chemotherapy is an important prognostic factor in patients with osteosarcoma (OS) and Ewing sarcoma (EWS). The aim of this study was to assess baseline primary tumour FDG uptake on PET/CT, and serum values of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), to establish whether these factors are correlated with tumour necrosis and prognosis.

Methods

Patients treated between 2009 and 2014 for localized EWS and OS, who underwent FDG PET/CT as part of their staging work-up, were included. The relationships between primary tumour SUVmax at baseline (SUV1), SUVmax after induction chemotherapy (SUV2), metabolic response calculated as [(SUV1???SUV2)/SUV1)]?×?100, LDH and ALP and tumour response/survival were analysed. A good response (GR) was defined as tumour necrosis >90 % in patients with OS, and grade II-III Picci necrosis (persitence of microscopic foci only or no viable tumor) in patients with Ewing sarcoma.

Results

The study included 77 patients, 45 with EWS and 32 with OS. A good histological response was achieved in 53 % of EWS patients, and 41 % of OS patients. The 3-year event-free survival (EFS) was 57 % in EWS patients and 48 % OS patients. The median SUV1 was 5.6 (range 0?–?17) in EWS patients and 7.9 (range 0?–?24) in OS patients (p?=?0.006). In EWS patients the GR rate was 30 % in those with a high SUV1 (≥6) and 72 % in those with a lower SUV1 (p?=?0.0004), and in OS patients the GR rate was 29 % in those with SUV1 ≥6 and 64 % in those with a lower SUV1 (p?=?0.05). In the univariate analysis the 3-year EFS was significantly better in patients with a low ALP level (59 %) than in those with a high ALP level (22 %, p?=?0.02) and in patients with a low LDH level (62 %) than in those with a high LDH level (37 %, p?=?0.004). In EWS patients the 3-year EFS was 37 % in those with a high SUV1 and 75 % in those with a low SUV1 (p?=?0.004), and in OS patients the 3-year EFS was 32 % in those with a high SUV1 and 66 % in those with a low SUV1 (p?=?0.1). Histology, age and gender were not associated with survival. In the multivariate analysis, SUV1 was the only independent pretreatment prognostic factor to retain statistical significance (p?=?0.017). SUV2 was assessed in 25 EWS patients: the median SUV2 was 1.9 (range 1?–?8). The GR rate was 20 % in patients with a high SUV2, and 67 % in those with a low SUV2 (p?=?0.02). A good metabolic response (SUV reduction of ≥55 %) was associated with a 3-year EFS of 80 % and a poor metabolic response with a 3-year EFS of 20 % (p?=?0.05). In the OS patients the median SUV2 was 2.7 (range 0?–?4.5). Neither SUV2 nor the metabolic response was associated with outcome in OS patients.

Conclusion

FDG PET/CT is a useful and noninvasive tool for identifying patients who are more likely to be resistant to chemotherapy. If this finding is confirmed in a larger series, SUV1, SUV2 and metabolic response could be proposed as factors for stratifying EWS patients to identify those with high-grade localized bone EWS who would benefit from risk-adapted induction chemotherapy.

     

Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor

Purpose

Metabolic activity and hypoxia are both important factors characterizing tumor aggressiveness. Here, we used F-18 fluoromisonidazole (FMISO) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to define metabolically active hypoxic volume, and investigate its clinical significance in relation to progression free survival (PFS) and overall survival (OS) in glioblastoma patients.

Experimental Design

Glioblastoma patients (n?=?32) underwent FMISO PET, FDG PET, and magnetic resonance imaging (MRI) before surgical intervention. FDG and FMISO PET images were coregistered with gadolinium-enhanced T1-weighted MR images. Volume of interest (VOI) of gross tumor volume (GTV) was manually created to enclose the entire gadolinium-positive areas. The FMISO tumor-to-normal region ratio (TNR) and FDG TNR were calculated in a voxel-by-voxel manner. For calculating TNR, standardized uptake value (SUV) was divided by averaged SUV of normal references. Contralateral frontal and parietal cortices were used as the reference region for FDG, whereas the cerebellar cortex was used as the reference region for FMISO. FDG-positive was defined as the FDG TNR ≥1.0, and FMISO-positive was defined as FMISO TNR ≥1.3. Hypoxia volume (HV) was defined as the volume of FMISO-positive and metabolic tumor volume in hypoxia (hMTV) was the volume of FMISO/FDG double-positive. The total lesion glycolysis in hypoxia (hTLG) was hMTV?×?FDG SUVmean. The extent of resection (EOR) involving cytoreduction surgery was volumetric change based on planimetry methods using MRI. These factors were tested for correlation with patient prognosis.

Results

All tumor lesions were FMISO-positive and FDG-positive. Univariate analysis indicated that hMTV, hTLG, and EOR were significantly correlated with PFS (p?=?0.007, p?=?0.04, and p?=?0.01, respectively) and that hMTV, hTLG, and EOR were also significantly correlated with OS (p?=?0.0028, p?=?0.037, and p?=?0.014, respectively). In contrast, none of FDG TNR, FMISO TNR, GTV, HV, patients’ age, or Karnofsky performance scale (KPS) was significantly correlated with PSF or OS. The hMTV and hTLG were found to be independent factors affecting PFS and OS on multivariate analysis.

Conclusions

We introduced hMTV and hTLG using FDG and FMISO PET to define metabolically active hypoxic volume. Univariate and multivariate analyses demonstrated that both hMTV and hTLG are significant predictors for PFS and OS in glioblastoma patients.

     

Impact of a second FDG PET scan before adjuvant therapy for the early detection of residual/relapsing tumours in high-risk patients with oral cavity cancer and pathological extracapsular spread

Purpose

Extracapsular spread (ECS) to the cervical lymph nodes is a major adverse prognostic factor in oral cavity squamous cell carcinoma (OSCC). We prospectively examined the value of FDG PET immediately before postoperative radiotherapy/concurrent chemoradiotherapy (pre-RT/CCRT PET) to detect residual/relapsing disease in the early postsurgical follow-up period in high-risk OSCC patients with ECS.

Methods

We examined 183 high-risk OSCC patients with ECS who underwent preoperative FDG PET/CT for staging purposes. Of these patients, 29 underwent a second pre-RT/CCRT FDG PET/CT scan. The clinical utility of the second FDG PET/CT was examined using Kaplan-Meier curve analysis.

Results

Patients who underwent the second FDG PET/CT scan had baseline clinicopathological characteristics similar to those who did not undergo a second scan. Of the patients who underwent the second scan, seven (24?%) had unexpected, newly discovered lesions. Five eventually died of the disease, and two had no evidence of recurrence after a change in RT field and dose. In an event-based analysis at 2?months, rates of neck control (6/29 vs. 6/154, p?=?0.001), distant metastases (3/29 vs. 4/154, p?=?0.046), and disease-free survival (7/29 vs. 10/154, p?=?0.003) were significantly higher in patients who received a second PET scan than in those who did not. The second pre-RT/CCRT PET scan was of particular benefit for detecting new lesions in OSCC patients with both ECS and lymph node standardized uptake value (SUV) of ≥5.2 in the first PET scan.

Conclusion

The present findings support the clinical value of pre-RT/CCRT FDG PET for defining treatment strategy in OSCC patients with both ECS and high nodal SUV, even when FDG PET had already been performed during the initial staging work-up.     

Diffusion-weighted MRI, 11C-choline PET and 18F-fluorodeoxyglucose PET for predicting the Gleason score in prostate carcinoma

Objectives

To evaluate the accuracy of transrectal ultrasound-guided (TRUS) biopsy, diffusion-weighted (DW) magnetic resonance imaging (MRI), ¹¹C-choline (CHOL) positron emission tomography (PET), and ¹⁸F-fluorodeoxyglucose (FDG) PET in predicting the prostatectomy Gleason risk (GR).

Methods

The study included 21 patients who underwent TRUS biopsy and multi-technique imaging before radical prostatectomy. Values from five different tests (TRUS biopsy, DW MRI, CHOL PET, FDG PET, and combined DW MRI/CHOL PET) were correlated with the prostatectomy GR using Spearman’s ρ. Tests that were found to have significant correlations were used to classify patients into GR groups.

Results

The following tests had significant correlations with prostatectomy GR: TRUS biopsy (ρ?=?0.617, P?=?0.003), DW MRI (ρ?=?–0.601, P?=?0.004), and combined DW MRI/CHOL PET (ρ?=?–0.623, P?=?0.003). CHOL PET alone and FDG PET only had weak correlations. The correct GR classification rates were 67 % with TRUS biopsy, 67 % with DW MRI, and 76 % with combined DW MRI/CHOL PET.

Conclusions

DW MRI and combined DW MRI/CHOL PET have significant correlations and high rates of correct classification of the prostatectomy GR, the strength and accuracy of which are comparable with TRUS biopsy.

Key Points

? Accurate determination of the Gleason score is essential for prostate cancer management. ? DW MRI ± CHOL PET correlated significantly with prostatectomy Gleason score. ? These correlations are similar to that between TRUS biopsy and prostatectomy.     

FDG PET as a prognostic predictor in the early post-therapeutic evaluation for unresectable hepatocellular carcinoma

Purpose

To elucidate the prognostic role of post-therapeutic ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET), we conducted a retrospective cohort study analysing the clinical factors that affect overall survival after non-operative therapy for unresectable hepatocellular carcinoma (HCC).

Methods

Sixty-seven cases with unresectable HCC who received non-operative therapy (transcatheter arterial chemoembolization: n?=?24, transcatheter arterial infusion chemotherapy: n?=?31, radiofrequency ablation: n?=?5 or systemic chemotherapy: n?=?7) and had received FDG PET for the evaluation of the therapeutic effect within 1 month after the end of the therapy were evaluated. Overall survival rate was evaluated using the univariate and multivariate analyses of relevant clinical and laboratory parameters before and after therapy, including visual PET analysis and quantitative analysis using maximum standardized uptake value (SUV).

Results

Visual PET diagnosis of post-therapeutic lesions was a good predictor of overall survival of unresectable HCC patients. The low FDG group showed significantly longer survival (average: 608 days) than that (average: 328 days) of the high FDG group (p?<?0.0001). Multivariate analysis showed four significant prognostic factors for the survival: post-therapeutic alpha-fetoprotein (αFP) level (=400 ng/ml, p?=?0.004), post-therapeutic visual PET diagnosis (p?=?0.006), post-therapeutic clinical stage (UICC stage IV, p?=?0.04) and post-therapeutic Milan criteria (p?=?0.03), while pre-therapeutic clinical factors, SUV by post-therapeutic FDG PET (5.0 or more) or others did not show significance.

Conclusion

The present study suggests that post-therapeutic PET performed within 1 month after non-operative therapy can be a good predictor of overall survival in unresectable HCC patients, while pre-therapeutic evaluation including PET, tumour markers and clinical staging may not be useful.     

Prognostic value of 18F-FDG PET/CT in patients with soft tissue sarcoma: comparisons between metabolic parameters

Objectives

To investigate the relationship between volume-based PET parameters and prognosis in patients with soft tissue sarcoma (STS).

Methods

We retrospectively reviewed 55 patients with pathologically proven STS who underwent pretreatment with ¹⁸?F-Fluorodeoxyglucose (¹⁸F-FDG) PET/CT. The maximum standardized uptake value (SUV_max), average SUV (SUV_avg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of primary tumors were measured using a threshold SUV as liver activity for determining the boundary of tumors. Univariate and multivariate survival analyses for overall survival were performed according to the metabolic parameters and other clinical variables.

Results

Cancer-related death occurred in 19 of 55 patients (35 %) during the follow-up period (29?±?23 months). On univariate analysis, AJCC stage (stage IV vs. I-III, hazard ratio (HR)?=?2.837, p?=?0.028), necrosis (G2 vs. G0-G1, HR?=?3.890, p?=?0.004), SUV_max (1 unit - increase, HR?=?1.146, p?=?0.008), SUV_avg (1 unit - increase, HR?=?1.469, p?=?0.032) and treatment modality (non-surgical therapy vs. surgery, HR?=?4.467, p?=?0.002) were significant predictors for overall survival. On multivariate analyses, SUV_max (HR?=?1.274, p?=?0.015), treatment modality (HR?=?3.353, p?=?0.019) and necrosis (HR?=?5.985, p?=?0.006) were identified as significant independent prognostic factors associated with decreased overall survival.

Conclusions

The SUV_max of the primary tumor is a significant independent metabolic prognostic factor for overall survival in patients with STS. Volume-based PET parameters may not add prognostic information outside of the SUV_max.     

Recurrent bladder carcinoma: clinical and prognostic role of 18 F-FDG PET/CT

Aim

A small number of studies evaluated the detection rate of lesions from bladder carcinoma (BC) of 18 F-FDG PET/CT in the restaging process. However, the prognostic role of FDG PET/CT still remains unclear. The aim of the present study was to evaluate the accuracy, the effect upon treatment decision, and the prognostic value of FDG PET/CT in patients with suspected recurrent BC.

Materials and Methods

Forty-one patients affected by BC underwent FDG PET/CT for restaging purpose. The diagnostic accuracy of visually interpreted FDG PET/CT was assessed compared to histology (n?=?8), other diagnostic imaging modalities (contrast-enhanced CT in 38/41 patients and MRI in 15/41) and clinical follow-up (n?=?41). Semiquantitative PET values (SUVmax, SUVmean, SUL, MTV, TLG) were calculated using a graph-based method. Progression-free survival (PFS) and overall survival (OS) were assessed by using Kaplan-Meier curves. The risk of progression (hazard ratio, HR) was computed by Cox regression analysis by considering all the available variables.

Results

PET was considered positive in 21 of 41 patients. Of these, recurrent BC was confirmed in 20 (95 %). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG PET/CT were 87 %, 94 %, 95 %, 85 %, 90 %. AUC was 0.9 (95 %IC 0.8-1). Bayesian positive and negative likelihood ratios were 14.5 and 0.13, respectively. FDG PET/CT findings modified the therapeutic approach in 16 patients (modified therapy in 10 PET-positive patients, watch-and-wait in six PET-negative patients). PFS was significantly longer in patients with negative scan vs. those with pathological findings (85 % vs. 24 %, p?<?0.05; HR?=?12.4; p?=?0.001). Moreover, an unremarkable study was associated with a longer OS (88 % vs. 47 % after 2 years and 87 % vs. 25 % after 3 years, respectively, p?<?0.05). Standardized uptake value (SUV)max?>?6 and total lesion glycolysis (TLG)?>?8.5 were recognized as the most accurate thresholds to predict PFS (2-year PFS 62 % for SUVmax?<?6 vs. 15 % for SUVmax?>?6, p?=?0.018; 2-year PFS 66 % for TLG?<?8.5 vs. 18 % for TLG?>?8.5, p?=?0.09).

Conclusion

A very good diagnostic performance for FDG PET/CT was confirmed in patients with suspected recurrent BC. FDG PET/CT allowed for a change in treatment decision in about 40 % of cases and showed an important prognostic value in assessing PFS and OS.

     

Correlation of high 18F-FDG uptake to clinical, pathological and biological prognostic factors in breast cancer

Purpose

The aim of this study was to determine the impact of the main clinicopathological and biological prognostic factors of breast cancer on ¹⁸F-fluorodeoxyglucose (FDG) uptake. Only women with tumours larger than 20?mm (T2?CT4) were included in order to minimize bias of partial volume effect.

Methods

In this prospective study, 132 consecutive women received FDG PET/CT imaging before starting neoadjuvant chemotherapy. Maximum standardized uptake values (SUV_max) were compared to tumour characteristics as assessed on core biopsy.

Results

There was no influence of T and N stage on SUV. Invasive ductal carcinoma showed higher SUV than lobular carcinoma. However, the highest uptake was found for metaplastic tumours, representing 5% of patients in this series. Several biological features usually considered as bad prognostic factors were associated with an increase in FDG uptake: the median of SUV_max was 9.7 for grade 3 tumours vs 4.8 for the lower grades (p?p?=?0.003); triple-negative tumours (oestrogen and progesterone receptor negative, no overexpression of c-erbB-2) had an SUV of 9.2 vs 5.8 for all others (p = 0005); p53 mutated tumours also had significantly higher SUV (7.8 vs 5.0; p?Conclusion Knowledge of the factors influencing uptake is important when interpreting FDG PET/CT scans. Also, findings that FDG uptake is highest in those patients with poor prognostic features (high grade, hormone receptor negativity, triple negativity, metaplastic tumours) is helpful to determine who are the best candidates for baseline staging.     

PET/MRI in head and neck cancer: initial experience

Purpose

To evaluate the feasibility of PET/MRI (positron emission tomography/magnetic resonance imaging) with FDG (¹⁸F-fluorodeoxyglucose) for initial staging of head and neck cancer.

Methods

The study group comprised 20 patients (16 men, 4 women) aged between 52 and 81?years (median 64?years) with histologically proven squamous cell carcinoma of the head and neck region. The patients underwent a PET scan on a conventional scanner and a subsequent PET/MRI examination on a whole-body hybrid system. FDG was administered intravenously prior to the conventional PET scan (267?C395?MBq FDG, 348?MBq on average). The maximum standardized uptake values (SUV_max) of the tumour and of both cerebellar hemispheres were determined for both PET datasets. The numbers of lymph nodes with increased FDG uptake were compared between the two PET datasets.

Results

No MRI-induced artefacts where observed in the PET images. The tumour was detected by PET/MRI in 17 of the 20 patients, by PET in 16 and by MRI in 14. The PET/MRI examination yielded significantly higher SUV_max than the conventional PET scanner for both the tumour (p?<?0.0001) and the cerebellum (p?=?0.0009). The number of lymph nodes with increased FDG uptake detected using the PET dataset from the PET/MRI system was significantly higher the number detected by the stand-alone PET system (64 vs. 39, p?=?0.001).

Conclusion

The current study demonstrated that PET/MRI of the whole head and neck region is feasible with a whole-body PET/MRI system without impairment of PET or MR image quality.     

The combination of FDG PET and dynamic contrast-enhanced MRI improves the prediction of disease-free survival in patients with advanced breast cancer after the first cycle of neoadjuvant chemotherapy

Purpose

The aim of this study was to investigate the potential of FDG PET/CT and MRI in predicting disease-free survival (DFS) after neoadjuvant chemotherapy (NAC) and surgery in patients with advanced breast cancer.

Methods

The analysis included 54 women with advanced breast cancer. All patients received three cycles of NAC, underwent curative surgery, and then received three cycles of additional chemotherapy. Before and after the first cycle of NAC, all patients underwent sequential PET/CT and MRI. All patients were analysed using a diverse range of parameters. including maximal standardized uptake value (SUV), percent change in SUV (ΔSUV), initial slope of the enhancement curve (MRslope), apparent diffusion coefficient (ADC), tumour size, change in MRslope (ΔMRslope), change in ADC (ΔADC), change in tumour size (Δsize) and other clinicopathological parameters]. The relationships between covariates and DFS after surgery were analysed using the Kaplan-Meier method and the multivariate Cox proportional hazards model. Time-dependent receiver operating characteristic curves were used to determine the optimal cut-off values of imaging parameters for DFS.

Results

Of the 54 patients, 13 (24 %) experienced recurrence at a median follow-up of 38 months (range 25 – 45 months). Univariate and multivariate analyses showed that a lesser decline in SUV, a lesser decline in MRslope, a lesser increase in ADC, and ER negativity were significantly associated with a poorer DFS (P?=?0.0006, ΔSUV threshold ?41 %; P?=?0.0016, ΔMRslope threshold ?6 %; P?=?0.011, ΔADC threshold 11 %; and P?=?0.0086, ER status, respectively). Patients with a combination of ΔSUV >?41 % and ΔMRslope >?6 % showed a significantly higher recurrence rate (77.8 %) than the remaining of patients (13.3 %, P?Conclusion Functional parameters of both FDG PET and MRI after the first cycle of NAC are useful for predicting DFS in patients with advanced breast cancer. This approach could lead to an improvement in patient care because ineffective NAC agents could be avoided and more aggressive therapy could be used in high-risk patients.     

The association of 18F-FDG PET/CT parameters with survival in malignant pleural mesothelioma

Purpose

Malignant pleural mesothelioma (MPM) is a disease with poor prognosis despite multimodal therapy but there is variation in survival between patients. Prognostic information is therefore potentially valuable in managing patients, particularly in the context of clinical trials where patients could be stratified according to risk. Therefore we have evaluated the prognostic ability of parameters derived from baseline 2-[¹⁸F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT).

Methods

In order to determine the relationships between metabolic activity and prognosis we reviewed all ¹⁸F-FDG PET/CT scans used for pretreatment staging of MPM patients in our institution between January 2005 and December 2011 (n?=?60) and measured standardised uptake values (SUV) including mean, maximum and peak values, metabolic tumour volume (MTV) and total lesion glycolysis (TLG). Overall survival (OS) or time to last censor was recorded, as well as histological subtypes.

Results

Median follow-up was 12.7 months (1.9–60.9) and median OS was 14.1 months (1.9–54.9). By univariable analysis histological subtype (p?=?0.013), TLG (p?=?0.024) and MTV (p?=?0.038) were significantly associated with OS and SUV_max was borderline (p?=?0.051). On multivariable analysis histological subtype and TLG were associated with OS but at borderline statistical significance (p?=?0.060 and 0.058, respectively). No statistically significant differences in any PET parameters were found between the epithelioid and non-epithelioid histological subtypes.

Conclusion

¹⁸F-FDG PET/CT parameters that take into account functional volume (MTV, TLG) show significant associations with survival in patients with MPM before adjusting for histological subtype and are worthy of further evaluation to determine their ability to stratify patients in clinical trials.     

18F-FDG PET/CT imaging versus dynamic contrast-enhanced CT for staging and prognosis of inflammatory breast cancer

Purpose

Inflammatory breast cancer (IBC) is the most aggressive type of breast cancer with a poor prognosis. Locoregional staging is based on dynamic contrast-enhanced (DCE) CT or MRI. The aim of this study was to compare the performances of FDG PET/CT and DCE CT in locoregional staging of IBC and to assess their respective prognostic values.

Methods

The study group comprised 50 women (median age: 51?±?11 years) followed in our institution for IBC who underwent FDG PET/CT and DCE CT scans (median interval 5?±?9 days). CT enhancement parameters were net maximal enhancement, net early enhancement and perfusion.

Results

The PET/CT scans showed intense FDG uptake in all primary tumours. Concordance rate between PET/CT and DCE CT for breast tumour localization was 92 %. No significant correlation was found between SUVmax and CT enhancement parameters in primary tumours (p?>?0.6). PET/CT and DCE CT results were poorly correlated for skin infiltration (kappa?=?0.19). Ipsilateral foci of increased axillary FDG uptake were found in 47 patients (median SUV: 7.9?±?5.4), whereas enlarged axillary lymph nodes were observed on DCE CT in 43 patients. Results for axillary node involvement were fairly well correlated (kappa?=?0.55). Nineteen patients (38 %) were found to be metastatic on PET/CT scan with a significant shorter progression-free survival than patients without distant lesions (p?=?0.01). In the primary tumour, no statistically significant difference was observed between high and moderate tumour FDG uptake on survival, using an SUVmax cut-off of 5 (p?=?0.7 and 0.9), or between high and low tumour enhancement on DCE CT (p?>?0.8).

Conclusion

FDG PET/CT imaging provided additional information concerning locoregional involvement to that provided by DCE CT on and allowed detection of distant metastases in the same whole-body procedure. Tumour FDG uptake or CT enhancement parameters were not correlated and were not found to have any prognostic value.     

Prognostic value of the standardized uptake value for 18F-fluorodeoxyglucose in patients with stage IIIB melanoma

Purpose

FDG PET/CT is an excellent tool to detect melanoma metastases and also allows quantification of FDG uptake using standardized uptake value (SUV). The aim of this study was to prospectively investigate the potential prognostic value of SUV for disease-free survival (DFS) and disease-specific survival (DSS) for patients with stage IIIB melanoma.

Methods

From November 2003 to March 2008, all consecutive patients were included in the present study. Inclusion criteria were: palpable, histology- or cytology-proven lymph node metastases of melanoma, and referred to the University Medical Centre Groningen for FDG PET and CT examination. Patients without distant metastases were evaluated. Multivariable survival analysis was performed to determine whether SUV was associated with DFS and DSS (Cox proportional hazard analysis).

Results

In 80 patients (without distant metastases, 65?%) SUV could be measured. Overall 5-year DFS was 41?% (95% CI 26–56?%) and 24?% (95% CI 12–38?%) in patients with a low and high SUVmean (p?=?0.02), respectively. Overall 5-year DSS was 48?% (95% CI 31–62?%) and 30?% (95% CI 17–45?%) in patients with a low and high SUVmean (p?=?0.04), respectively. In the multivariable analysis, SUVmean was associated with DFS (hazard ratio 1.7; p?=?0.048), but was not associated with DSS (hazard ratio 1.6; p?=?0.1). The number of positive nodes, extranodal growth and gender were also associated with survival.

Conclusion

FDG uptake in clinically overt nodal melanoma metastases is inversely associated with DFS. Univariate analysis showed an association with DSS. However, after adjustment for potential confounders this association was no longer significant. If these findings are confirmed in larger studies, SUVmean could potentially be used (in addition to the number of positive nodes, tumour size and extranodal growth) as a factor in deciding on adjuvant systemic treatment.     

Evaluation of early response to concomitant chemoradiotherapy by interim 18F-FDG PET/CT imaging in patients with locally advanced oesophageal carcinomas

Purpose

The best way to assess the response to chemoradiotherapy of locally advanced oesophageal carcinomas is not known. We used ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT to evaluate the metabolic response during chemoradiotherapy and tried to correlate this response to survival.

Methods

Patients with biopsy-proven oesophageal carcinoma underwent FDG PET/CT with evaluation of the standardized uptake value (SUV) before any treatment (SUV1) and during chemoradiotherapy after two cycles of 5-fluorouracil (FU)/cisplatin and 20 Gy (SUV2). Metabolic response was defined as 1?(SUV2/SUV1). Surgery was discussed after 40 Gy and three cycles of chemotherapy. Results of interim PET were not considered for the therapeutic decision.

Results

Among 72 patients who underwent a first FDG PET/CT before any treatment, 59 (82 %) could receive the second FDG PET/CT examination. Median survival was 22.2 months with 1-year and 2-year survivals of 70 and 46 %, respectively. Nineteen patients (32 %) underwent surgery. Mean SUV1 and SUV2 were 12.3?±?6.2 and 6?±?4.1, respectively (p?<?0.001). Using a cut-off for metabolic response of 50 %, sensitivity and specificity for survival were 0.7 and 0.58. The 2-year overall survival of good responders was 62 % as compared to 27 % for poor metabolic responders. A multivariate analysis was performed, including T and N stages, surgery, histology and metabolic response: only metabolic response was significantly (p?=?0.009) associated with 2-year survival.

Conclusion

Early evaluation of metabolic response had a great prognostic value and could help identify good responders to chemoradiotherapy.     

18F-FDG PET SUVmax as an indicator of histopathologic response after neoadjuvant chemotherapy in extremity osteosarcoma

Purpose

This study evaluated the usefulness of the maximum standardized uptake value (SUVmax) as a measure of histologic response to neoadjuvant chemotherapy in patients with extremity osteosarcoma. The correlation between [¹⁸?F]FDG PET SUVmax values and histologic response to preoperative chemotherapy was also assessed prospectively using PET/MRI.

Methods

A total of 26 consecutive patients with high-grade osteosarcoma were prospectively enrolled. All patients underwent parallel PET and MRI scans before and after neoadjuvant chemotherapy. Using the PET and MRI images and pathologic mapping, we assessed the percentage necrosis by histology at the highest metabolic activity point in the tumors. This was defined as the minimum histologic response. The predictive values of SUVmax before (SUV1) and after (SUV2) chemotherapy and the SUV change ratio were determined. Correlations were also investigated among SUV2, minimum histologic response and histologic response.

Results

Histologically, 13 patients were classified as good responders and 13 as poor responders. Patients with an SUV2 of >5 showed a poor histologic response. A significant correlation was found between SUV2 and histologic response (Spearman’s rho ?0.642; P?<?0.001), and SUV2 and histologic response were both found to be significantly correlated with minimum histologic response (Spearman’s rho ?0.515 and 0.911; P?=?0.007 and P?<?0.001, respectively).

Conclusion

A SUVmax of more than 5 after neoadjuvant chemotherapy identified the majority of histologic nonresponders (sensitivity 61.3 %, PPV 88.9 %). Tumor necrosis at the point of maximum metabolic activity was found to be significantly correlated with the histologic response of entire resected specimen.     

Correlation of <Superscript>18</Superscript>F-FDG and <Superscript>11</Superscript>C-methionine uptake on PET/CT with Ki-67 immunohistochemistry in newly diagnosed intracranial meningiomas

Objective

We evaluated the uptake of 2-deoxy-2-¹⁸F-fluoro-d-glucose (FDG) and l-[methyl-¹¹C]-methionine (MET) in patients with newly diagnosed intracranial meningiomas and correlated the results with tumor proliferation.

Methods

Data from 22 patients with newly diagnosed intracranial meningioma (12 grade I and 10 grade II) who underwent both FDG and MET brain PET/CT studies were retrospectively analyzed. The PET images were evaluated by a qualitative method and semiquantitative analysis using standardized uptake value (SUV) (SUV_max and SUV_peak) and tumor-to-reference tissue ratio (T_max/N ratio and T_peak/N ratio). Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens.

Results

MET PET/CT showed a higher detection rate of meningioma than did FDG PET/CT (100 vs. 46%, respectively). The T_max/N ratio and T_peak/N ratio on MET PET/CT were significantly higher than those on FDG PET/CT (p?<?0.001 and p?<?0.001, respectively). There was a significant difference between grades I and II with respect to FDG SUVmax (p?=?0.003), FDG SUV_peak (p?=?0.003), FDG T_max/N ratio (p?=?0.02), FDG T_peak/N ratio (p?=?0.006), MET SUV_max (p?=?0.002), MET SUV_peak (p?=?0.002), MET T_max/N ratio (p?=?0.002), and MET T_peak/N ratio (p?=?0.002). There was a significant correlation between Ki-67 index and FDG PET/CT for SUV_max (p?=?0.02), SUV_peak (p?=?0.005), and T_peak/N ratio (p?=?0.05) and between Ki-67 index and MET PET/CT for SUV_max (p?=?0.004), SUV_peak (p?=?0.007), T_max/N ratio (p?=?0.002), and T_peak/N ratio (p?=?0.004).

Conclusion

MET PET/CT showed a high sensitivity compared with FDG PET/CT for detection of newly diagnosed WHO grades I and II intracranial meningiomas. Both FDG and MET uptake were found to be useful for evaluating tumor proliferation in meningiomas.

     

Postchemotherapy PET evaluation correlates with patient outcome in paediatric Hodgkin��s disease

Aim

To evaluate the role of postchemotherapy FDG PET and compare it with other predictive factors in paediatric Hodgkin??s disease (HD).

Materials and methods

In this retrospective study, 98 paediatric patients with HD (enrolled in eight Italian centres) were analysed. Their mean age was 13.8?years (range 5?C19?years). A PET scan was performed at the end of chemotherapy and reported as positive or negative on the basis of visual and/or semiquantitative analysis. True outcome was defined as remission or disease on the basis of combined criteria (clinical, instrumental and/or histological) with a mean follow-up period of 25?months. Statistical analyses were performed for the postchemotherapy PET results and other potential predictive factors (age cut-off, stage, presence of bulky masses and therapeutic group) with respect to patient outcome and progression-free survival (PFS).

Results

Overall the patients had a mean PFS of 23.5?months (range 4?C46?months): 87 achieved remission (88.8%) and 11 showed disease. Of the 98 patients, 17 were positive on postchemotherapy PET . Seven patients (41%) showed disease during follow-up, and relapse occurred in only four out of the 81 patients who were negative on PET (p?=?0.0001). Kaplan-Meier analysis demonstrated significant correlations between PFS and the postchemotherapy PET result (p?=?0.0001) and a cut-off age at diagnosis of 13.3?years (p?=?0.0337), whereas disease stage (p?=?0.7404), therapeutic group (p?=?0.5240) and presence of bulky masses (p?=?0.2208) were not significantly correlated with PFS. Multivariate analysis confirmed a statistically significant correlation with PFS only for the postchemotherapy PET findings (p?=?0.0009).

Conclusion

In paediatric HD, age at diagnosis and postchemotherapy PET results are the main predictors of patient outcome and PFS, with FDG PET being the only independent predictive factor for PFS.     

Diagnostic Value of <Superscript>18</Superscript>F-FDG PET/CT and MRI in the Preoperative Evaluation of Uterine Carcinosarcoma

Purpose

This study aimed to compare the diagnostic value of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and magnetic resonance imaging (MRI) in the preoperative evaluation of uterine carcinosarcoma.

Methods

Fifty-four women with pathologically confirmed uterine carcinosarcoma who underwent preoperative FDG PET/CT and MRI from June 2006 to November 2016 were included. Pathologic findings from primary tumor lesions, para-aortic and pelvic lymph node (LN) areas, and peritoneal seeding lesions were compared with the FDG PET/CT and MRI findings. The maximum standardized uptake value (SUVmax) of the primary tumor and LN was obtained. The tumor-to-liver ratio (TLR) was calculated by dividing the SUVmax of the primary tumor or LN by the mean SUV of the liver.

Results

For detecting primary tumor lesions (n?=?54), the sensitivity and accuracy of FDG PET/CT (53/54) and MRI (53/54) were 98.2%. The sensitivity, specificity, and accuracy of FDG PET/CT versus MRI were as follows: 63.2% (12/19) versus 26.3% (5/19), 100% (35/35) versus 100% (35/35), and 87.0% versus 74.0%, respectively, for pelvic LN areas (p?=?0.016); 85.7% (12/14) versus 42.9% (6/14), 90% (36/40) versus 97.5% (39/40), and 88.9% versus 83.3%, respectively, for para-aortic LN areas (p?=?0.004); and 59.4% (19/32) versus 50% (16/32), 100% (22/22) versus 100% (22/22), and 75.9% versus 70.4%, respectively, for peritoneal seeding lesions (p?=?0.250). For distant metastasis, the sensitivity, specificity, and accuracy of FDG PET/CT were 100 (8/8), 97.8 (45/46), and 98.2%, respectively.

Conclusions

FDG PET/CT showed superior diagnostic accuracy compared to MRI in detecting pelvic and para-aortic LN metastasis in patients with uterine carcinosarcoma. Moreover, FDG PET/CT facilitated the identification of distant metastasis.

     

18F-FAMT in patients with multiple myeloma: clinical utility compared to 18F-FDG

Objective

l-[3-¹⁸F]-alpha-methyltyrosine (¹⁸F-FAMT) is an amino-acid tracer for positron emission tomography (PET), with uptake related to overexpression of L-type amino-acid transporter 1 and proliferative activity in tumour cells. This study evaluated the diagnostic performance of ¹⁸F-FAMT PET compared with 2-[¹⁸F]-fluoro-2-deoxy-d-glucose (¹⁸F-FDG) PET in patients with multiple myeloma (MM).

Methods

Eleven patients with MM (newly diagnosed, n?=?3; relapsed after treatment, n?=?8) underwent whole-body ¹⁸F-FAMT and ¹⁸F-FDG PET within a 2-week interval. Magnetic resonance imaging (MRI) of the spine was also performed to assess patterns of bone marrow infiltration. Tracer uptake was semi-quantitatively evaluated using maximal standardized uptake value (SUV_max). Mean SUV was also determined for normal bone marrow and the aortic arch as mediastinal background SUV to calculate lesion-to-bone marrow (L/B) and lesion-to-mediastinum (L/M) ratios, respectively. Those values were statistically compared using Student??s t test.

Results

In 8 patients showing focal infiltration on MRI, 34 FDG-avid bone lesions were identified, with each showing increased FAMT uptake. Mean SUV_max and L/B ratio of FDG (3.1?±?1.2 and 3.3?±?1.9, respectively) were significantly higher than those of FAMT (2.0?±?1.0 and 2.6?±?1.1, respectively; p?<?0.05 each). In contrast, the L/M ratio of FDG showed no significant difference to that of FAMT (2.2?±?1.0 and 2.4?±?1.2, respectively; p?=?0.3).

Conclusions

Clear ¹⁸F-FAMT PET uptake was seen in most ¹⁸F-FDG-avid lesions among patients with MM, and an equivalent semi-quantitative value was obtained using L/M ratio. Our preliminary data suggest that ¹⁸F-FAMT PET provides a useful imaging modality for detecting active myelomatous lesions.     

The Role of F-18 FDG PET/CT in Intrahepatic Cholangiocarcinoma

Purpose

The aim of this study was to evaluate the diagnostic and prognostic role of metabolic parameters of FDG PET/CT in patients with intrahepatic cholangiocarcinoma (ICC).

Methods

From December 2008 to December 2013, 76 FDG PET/CT scans performed for initial staging of ICC in a single institution (57 male and 19 female; mean age 68?±?9 years) were retrospectively reviewed. Patients with history of other known malignancy were excluded. Detection rates of regional lymph node and distant metastasis by FDG PET/CT were analyzed in comparison with conventional imaging modalities such as CT or MRI. Metabolic parameters including maximum, peak and mean standardized uptake values (SUVmax, SUVpeak, SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), glucose corrected SUV (SUVgluc), and glucose corrected TLG (TLGgluc) were measured for the primary tumor. Cut-off values for the metabolic parameters were calculated by ROC curve analysis, and used to dichotomize the patient groups. The overall survival time (OS) was calculated and compared using the Cox proportional hazard regression analysis.

Results

The median duration of follow-up period was 5.4 months (interquartile range: 1.45～15.45). FDG PET/CT showed higher sensitivity than conventional imaging modalities in detection of regional node involvement (74.5 % vs. 61.8 %, p?=?0.013). In six patients, distant metastasis was identified only by FDG PET/CT. The mean SUVmax, SUVpeak, SUVmean, MTV, and TLG for the primary tumor were 8.2?±?3.1, 6.8?±?2.5, 4.0?±?0.8, 192.7?±?360.5 cm³, and 823.7?±?1615.4, respectively. Patients with higher (≥7.3, HR: 4.280, p?=?0.001), higher SUVpeak (≥6.5, HR: 2.333, p?=?0.020), higher SUVmean (≥3.9, HR: 2.799, p?=?0.004), higher SUVgluc (≥8.1, HR: 2.648, p?=?0.012), and higher TLGgluc (≥431.6, HR: 2.186, p?=?0.030) showed significantly shorter survival time. By multivariate study, operability was an independent prognostic factor for longer survival (HR: 4.113, p?=?0.005).

Conclusion

FDG PET/CT is an important diagnostic imaging tool in the nodal staging and detection of distant metastasis in ICC patients. Metabolic parameters may have a significant role as prognostic factors in patients with ICC.