Sequential 18F-FDG PET/CT for early prediction of complete pathological response in breast and axilla during neoadjuvant chemotherapy

Purpose

To investigate the value of response monitoring in both the primary tumour and axillary nodes on sequential PET/CT scans during neoadjuvant chemotherapy (NAC) for predicting complete pathological response (pCR), taking the breast cancer subtype into account.

Methods

In 107 consecutive patients 290 PET/CT scans were performed at baseline (PET/CT1, 107 patients), after 2 – 3 weeks of chemotherapy (PET/CT2, 85 patients), and after 6 – 8 weeks (PET/CT3, 98 patients). The relative changes in SUVmax (from baseline) of the tumour and the lymph nodes and in both combined (after logistic regression), and the changes in the highest SUVmax between scans (either tumour or lymph node) were determined and their associations with pCR of the tumour and lymph nodes after completion of NAC were assessed using receiver operating characteristic (ROC) analysis.

Results

A pCR was seen in 17 HER2-positive tumours (65 %), 1 ER-positive/HER2-negative tumour (2 %), and 16 triple-negative tumours (52 %). The areas under the ROC curves (ROC-AUC) for the prediction of pCR in HER2-positive tumours after 3 weeks were 0.61 for the relative change in tumours, 0.67 for the combined change in tumour and nodes, and 0.72 for the changes in the highest SUVmax between scans. After 8 weeks equivalent values were 0.59, 0.42 and 0.64, respectively. In triple-negative tumours the ROC-AUCs were 0.76, 0.84 and 0.76 after 2 weeks, and 0.87, 0.93 and 0.88 after 6 weeks, respectively.

Conclusion

In triple-negative tumours a PET/CT scan after 6 weeks (three cycles) appears to be optimally predictive of pCR. In HER2-positive tumours neither a PET/CT scan after 3 weeks nor after 8 weeks seems to be useful. The changes in SUVmax of both the tumour and axillary nodes combined correlates best with pCR.     

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.     

N staging of lung cancer patients with PET/MRI using a three-segment model attenuation correction algorithm: Initial experience

Objectives

Evaluate the performance of PET/MRI at tissue interfaces with different attenuation values for detecting lymph node (LN) metastases and for accurately measuring maximum standardised uptake values (SUVmax) in lung cancer patients.

Materials and Method

Eleven patients underwent PET/CT and PET/MRI for staging, restaging or follow-up of suspected or known lung cancer. Four experienced readers determined the N stage of the patients for each imaging method in a randomised blinded way. Concerning metastases, SUVmax of FDG-avid LNs were measured in PET/CT and PET/MRI in all patients. A standard of reference was created with a fifth experienced independent reader in combination with a chart review. Results were analysed to determine interobserver agreement, SUVmax correlation between CT and MRI (three-segment model) attenuation correction and diagnostic performance of the two techniques.

Results

Overall interobserver agreement was high (κ?=?0.86) for PET/CT and substantial (κ?=?0.70) for PET/MRI. SUVmax showed strong positive correlation (Spearman’s correlation coefficient = 0.93, P?<?0.001) between the two techniques. Diagnostic performance of PET/MRI was slightly inferior to that of PET/CT, without statistical significance (P?>?0.05).

Conclusions

PET/MRI using three-segment model attenuation correction for LN staging in lung cancer shows a strong parallel to PET/CT in terms of SUVmax, interobserver agreement and diagnostic performance.

Key Points

?F18-FDG PET/MRI shows similar performance to F18-FDG PET/CT in lung cancer N staging. ?PET/MRI has substantial interobserver agreement in N staging. ?A three-segment model attenuation correction is reliable for assessing the mediastinum.     

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.     

Increased FDG uptake in breast cancer is associated with prognostic factors

Purpose

To evaluate the relationship between FDG uptake and prognostic factors of breast cancer such as hormone receptors (estrogen and progesterone), expression of c-erbB-2, axillary lymph node status, tumor histology, grade and size.

Materials and methods

Between May 2009 and February 2011; 79 patients (mean age?±?SD: 52.9?±?13.9?years) with biopsy proven breast cancer underwent F-18 FDG PET/CT scanning for staging. Patients with excisional biopsy or neoadjuvant chemotherapy were excluded from the study. Histological types included were invasive ductal carcinoma (n?=?68), invasive lobular carcinoma (n?=?2), and invasive ductal plus lobular mixed carcinoma (n?=?9). Maximum standardized uptake values (SUVmax) were compared with estrogen (ER) and progesterone receptors (PR), expression of c-erbB-2, as well as tumor grade and tumor size. For the evaluation of relationship between tumor SUVmax values and prognosticators such as hormone receptors, tumor histologic grade, and tumor size, statistical analyses were performed using Student t test, Mann?CWhitney U Test and Pearson correlation coefficient and p values of less than 0.05 were considered to indicate statistically significant differences.

Results

All primary breast neoplasms were detected by PET/CT scanner. The mean SUVmax values and breast cancer tumor sizes ranged from 2.09 to 39.0 and 0.7 to 10?cm, respectively. Tumors with negative ER [(n?=?19); SUVmax median (min?Cmax): 15 (2.09?C39.0)] were associated with higher SUVmax values (p?=?0.01). Tumors with overexpression of C-erbB-2 [(n?=?28); SUVmax median (min?Cmax): 16.0 (5.0-39.0)]; tumor grade 3 [(n?=?25); SUVmax median (min?Cmax): 15 (6.43?C39)]; axillary lymph node involvement [(n?=?60); SUVmax median (min?Cmax): 13.61 (4.0?C39.0)]; tumor histopathology and increased tumor size were associated with higher maximum standardized uptake values. However, PR did not show any relationship with SUVmax values.

Conclusion

In the present report, strong relationships were detected between the negativity of ER, overexpression of c-erbB-2, tumor grade, tumor size, histopathology, axillary lymph node involvement and SUVmax values. Accordingly, we believe that SUVmax values obtained with ¹⁸F-FDG PET/CT may provide some information about tumor biology of breast cancer.     

Diagnostic performance of 18F-fluorothymidine PET/CT for primary colorectal cancer and its lymph node metastasis: comparison with 18F-fluorodeoxyglucose PET/CT

Purpose

To examine the diagnostic performance of ¹⁸F-fluorothymidine (FLT) PET/CT in primary and metastatic lymph node colorectal cancer foci in comparison with ¹⁸F-fluorodeoxyglucose (FDG) PET/CT.

Methods

The study population comprised 28 patients with 30 newly diagnosed colorectal cancers who underwent surgical resection of the primary lesion and regional lymph nodes after both FLT and FDG PET/CT. The associations between SUVmax levels and pathological factors were evaluated using the Mann-Whitney U or Kruskal-Wallis test. Differences in diagnostic indexes for detecting nodal metastasis between the two tracers were estimated using the McNemar exact or χ ² test.

Results

All 30 primary cancers (43.0?±?20.0 mm, range 14 – 85 mm) were visualized by both tracers, but none of the FLT SUVmax values exceeded the FDG SUVmax values in any of the primary cancers (6.6?±?2.4 vs. 13.6?±?5.8, p?<?0.001). The sensitivity, specificity and accuracy for detecting nodal metastasis were 41 % (15/37), 98.8 % (493/499) and 94.8 % (508/536) for FDG PET/CT, and 32 % (12/37), 98.8 % (493/499) and 94.2 % (505/536) for FLT PET/CT, respectively. The sensitivity (p?=?0.45), specificity (p?=?0.68) and accuracy (p?=?0.58) were not different between the tracers. Nodal uptake of FLT and FDG was discordant in 7 (19 %) of 37 metastatic nodes. There were ten concordant true-positive nodes of which six showed higher FDG SUVmax and four showed higher FLT SUVmax, but the difference between FDG and FLT SUVmax was not significant (5.56?±?3.55 and 3.62?±?1.45, respectively; p?=?0.22).

Conclusion

FLT has the same potential as FDG in PET/CT for the diagnosis of primary and nodal foci of colorectal cancer despite significantly lower FLT uptake in primary foci.     

Prognostic relevance at 5 years of the early monitoring of neoadjuvant chemotherapy using 18F-FDG PET in luminal HER2-negative breast cancer

Purpose

The objective of this study was to evaluate, in the luminal human epidermal growth factor receptor 2 (HER2)-negative breast cancer subtype, the prognostic value of tumour glucose metabolism at baseline and of its early changes during neoadjuvant chemotherapy (NAC).

Methods

This prospective study included 61 women with hormone-sensitive HER2-negative breast cancer treated with NAC. ¹⁸F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed at baseline. Hepatic activity was used as a reference to distinguish between low metabolic and hypermetabolic tumours. In hypermetabolic tumours, a PET exam was repeated after the first course of NAC. The relative change in the maximum standardized uptake value of the tumour (?SUV) was calculated.

Results

Nineteen women had low metabolic luminal breast cancers at baseline, correlated with low proliferation indexes. Forty-two women had hypermetabolic tumours, corresponding to more proliferative breast cancers with higher Ki-67 expression (p?=?0.017) and higher grade (p?=?0.04). The median follow-up period was 64.2 months (range 11.5–93.2). Thirteen women developed recurrent disease, nine of whom died. Worse overall survival was associated with larger tumour size [>5 cm, hazard ratio (HR)?=?6.52, p?=?0.009] and with hypermetabolic tumours achieving a low metabolic response after one cycle of NAC (ΔSUV?<?16 %, HR?=?10.63, p?=?0.004). Five-year overall survival in these poor responder patients was 49.2 %. Overall survival in women with low metabolic tumours or hypermetabolic/good response tumours was 100 and 96.15 %, respectively.

Conclusion

In luminal HER2-negative breast tumours, tumour metabolism at baseline and changes after the first course of NAC are early surrogate markers of patients’ survival. A subgroup of women with hypermetabolic/poorly responding tumours, correlated with poor prognosis at 5 years, can be identified early. These results may guide future studies by tailoring the NAC regimen to the metabolic response.     

Prognostic value of volumetric parameters measured by 18F-FDG PET/CT in patients with head and neck squamous cell carcinoma

Purpose

The objective of this study was to investigate the value of metabolic tumour volume (MTV) assessed with ¹⁸F-FDG PET/CT in predicting event-free survival (EFS) and overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC), and particularly to compare it with more conventional parameters such as maximum standardized uptake value (SUVmax).

Methods

Patients referred to our department for ¹⁸F-FDG PET/CT for staging of HNSCC were prospectively included between February 2009 and March 2011. Each patient was scanned using a Philips Gemini PET/CT system at 1 h after injection. The MTV was calculated semiautomatically for the primary site using methods based on SUV with various thresholds: 3-D contour around voxels equal to or greater than 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5 and 7.0 times SUV, or more than 30 %, 40 % and 50 % of SUVmax. ROC analysis was used to test the statistical significance of the differences among the calculated MTVs. EFS and OS were determined using the Kaplan-Meier method and compared with MTV in univariate and multivariate analyses, including the usual prognostic factors: age, sex, primary site, treatment, SCC histologic grade, AJCC stage, TNM classification, tumour SUVmax and SUVpeak.

Results

The study included 80 consecutive patients (70 men, 10 women; mean age 62.4?±?9.0 years). ROC analysis revealed that pretreatment MTV using a threshold of 5.0 times SUV (MTV5.0) was the best parameter to predict recurrence and death after treatment. In univariate analysis, MTV5.0 >4.9 ml was predictive of poor EFS (p?<?0.0001) and poor OS (p?<?0.0001). In multivariate, MTV5.0 persisted as an independent predictive factor for EFS (p?=?0.011) and OS (p?=?0.010), while SUVmax became nonsignificant (p?=?0.277 for EFS, p?=?0.975 for OS).

Conclusion

Our results suggest that MTV measured by ¹⁸F-FDG PET/CT has independent prognostic value of in patients with HNSCC, stronger than SUVmax.     

The value of 18F-FDG PET/CT for assessing the response to neoadjuvant therapy in locally advanced rectal cancer

Purpose

Neoadjuvant radiochemotherapy (RCT) is an accepted treatment for locally advanced rectal cancer (LARC) that improves surgical outcomes. If a pathological complete response is achieved, conservative surgery can be considered. The objective of our study was to assess the reliability of ¹⁸F-FDG PET/CT for evaluating the response to neoadjuvant RCT in LARC.

Methods

We prospectively studied 41 patients diagnosed with LARC and candidates for neoadjuvant RCT. PET/CT was performed before RCT and again 7?weeks later. A visual and semiquantitative analysis was carried out. The pathological response was classified according to the Mandard tumour regression grade (TRG). We analysed: (a) the relationship between TRG and the result of the posttreatment PET/CT scan, and (b) the correlation between the percentage of pathological response and the percentage decrease in SUVmax according to the response index (RI).

Results

The mean SUVmax of the rectal lesions at diagnosis was 13.6 and after RCT 3.96. The mean RI was 65.32?%. Sensitivity was 88.88?%, specificity 92.86?%, positive predictive value 96?%, negative predictive value 81?%. Of the 41 patients, 8 had TRG I (all negative PET/CT); 6 had TRG II (5 negative, 1 positive PET/CT); 16 had TRG III (13 positive, 3 negative PET/CT); 9 had TRG IV (all positive PET/CT); 2 had TRG V (all positive PET/CT). Of the 14 patients classified as responders (TRG I, II), 13 (92.86?%) had negative PET/CT. Of the 27 patients classified as nonresponders (TRG III?CV), 24 (88.88?%) had positive PET/CT. Differences were statistically significant (p?<?0.0001). The RI in responders was 79.9?% and in nonresponders was 60.3?%. Differences were statistically significant (p?<?0.037).

Conclusion

PET/CT is a reliable technique for assessing response to neoadjuvant RCT in LARC, with a view to considering more conservative surgical treatment. The combination of the visual and semiquantitative analysis increases the diagnostic validity of PET/CT.     

18F-FDG PET/CT-based treatment response evaluation in locally advanced rectal cancer: a prospective validation of long-term outcomes

Purpose

To prospectively evaluate the usefulness of ¹⁸F-FDG PET/CT) imaging for predicting histopathological response and long-term clinical outcomes in locally advanced rectal cancer (LARC).

Methods

This prospective study included 38 patients with a confirmed diagnosis of LARC (cT3-4 or cN+) who underwent ¹⁸F-FDG PET/CT before and after neoadjuvant therapy (NAT). Total mesorectal excision was scheduled 6 weeks after NAT and was followed by an expert histopathological analysis of the surgical specimen. Baseline variables and previously identified maximum FDG standardized uptake value (SUVmax) cut-off values before NAT (SUVmax_PRE ≥6) and after NAT (SUVmax_POST ≥2), and the absolute and percentage reductions from baseline SUVmax (?SUVmax <4 and ?SUVmax% <65 %, respectively) were applied to differentiate patients showing a metabolic tumour response from nonresponders. These features were correlated with tumour regression grade (TRG), disease-free survival (DFS) and overall survival (OS).

Results

Significantly higher 5-year DFS and OS were seen in 19 responders (TRG 3 or 4) than in 19 nonresponders (TRG 0–2; 94.4 vs. 48.8 %, p?=?0.001; 94.7 vs. 63.2 %, p?=?0.02, respectively). In multivariate analysis the only PET/CT SUVmax-based parameter significantly correlated with the likelihood of recurrence and survival was ?SUV% <65 % (HR?=?5.95, p?=?0.02, for DFS; HR?=?5.26, p?=?0.04, for OS)

Conclusion

This prospective study proved that ¹⁸F-FDG PET/CT is a valuable imaging tool for assessing rectal cancer TRG and long-term prognosis, and could potentially serve as an intermediate endpoint in treatment optimization research and rectal cancer patient care.     

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.     

Evaluation of lymph node status after neoadjuvant chemotherapy in breast cancer patients: comparison of diagnostic performance of ultrasound,MRI and 18F-FDG PET/CT

Objective:

To evaluate the diagnostic performance of ultrasound, MRI and fluorine-18 fludeoxyglucose positron emission tomography (¹⁸F-FDG PET)/CT for the diagnosis of metastatic axillary lymph node (ALN) after neoadjuvant chemotherapy (NAC) and to find out histopathological factors affecting the diagnostic performance of these imaging modalities.

Methods:

From January 2012 to November 2014, 191 consecutive patients with breast cancer who underwent NAC before surgery were retrospectively reviewed. We included 139 patients with ALN metastasis that was confirmed on fine needle aspiration or core needle biopsy at initial diagnosis.

Results:

After NAC, 39 (28%) patients showed negative conversion of ALN on surgical specimens of sentinel lymph node (LN) or ALN. The sensitivity of ultrasound, MRI and PET/CT was 50% (48/96), 72% (70/97) and 22% (16/73), respectively. The specificity of ultrasound, MRI and PET/CT was 77% (30/39), 54% (21/39) and 85% (22/26), respectively. The Az value of combination of ultrasound and PET/CT was the highest (0.634) followed by ultrasound (0.626) and combination of ultrasound, MRI and PET/CT (0.617). The size of tumour deposit in LN and oestrogen receptor was significantly associated with the diagnostic performance of ultrasound (p < 0.001 and p = 0.009, respectively) and MRI (p = 0.045 and p = 0.036, respectively). The percentage diameter decrease, size of tumour deposit in LN, progesterone receptor, HER2 and histological grade were significantly associated with the diagnostic performance of PET/CT (p = 0.023, p = 0.002, p = 0.036, p = 0.044 and p = 0.008, respectively). On multivariate logistic regression analysis, size of tumour deposit within LN was identified as being independently associated with diagnostic performance of ultrasound [odds ratio, 13.07; 95% confidence interval (CI), 2.95–57.96] and PET/CT (odds ratio, 6.47; 95% CI, 1.407–29.737).

Conclusion:

Combination of three imaging modalities showed the highest sensitivity, and PET/CT showed the highest specificity for the evaluation of ALN metastasis after NAC. Ultrasound alone or combination of ultrasound and PET/CT showed the highest positive-predictive value. The size of tumour deposit within ALN was significantly associated with diagnostic performance of ultrasound and PET/CT.

Advances in knowledge:

This study is about the diagnostic performance of ultrasound, MRI, PET/CT and combination of each imaging modality for the evaluation of metastatic ALN after NAC. Of many histopathological factors, only the size of tumour deposit within ALN was an independent factor associated with the diagnostic performance of ultrasound and PET/CT.Axillary lymph node (ALN) metastasis is one of the most significant prognostic factors in patients with breast cancer. As the management of axillary lesions has been diverse, the detection of axillary nodal lesion has been more important. The diagnostic accuracy of ultrasound and MRI for the detection of metastatic ALNs has been studied by many researchers. Sensitivity and specificity of ultrasound for the detection of metastatic ALNs have been reported as 41.2–70.8% and 54.5–93.7%.^1–4 Sensitivity and specificity of MRI have been reported as 36–79% and 93–100%, respectively.^4–6Neoadjuvant chemotherapy (NAC) has become the standard treatment not only in patients with locally advanced breast cancer but also in early invasive breast cancer in an attempt to downstage the primary cancer and to reduce micrometastasis. If the ALN metastasis is confirmed on fine needle aspiration biopsy (FNAB) or core needle biopsy (CNB) at initial diagnosis, ALN dissection (ALND) is usually performed, regardless of the responsiveness of ALN. Residual metastatic lesion of ALNs after NAC is an important prognostic factor of disease-free survival.^7,8In ACOSOG Z1071 trial, in patients with breast cancer with clinical N1 stage receiving NAC, if two or more sentinel lymph nodes (SLNs) were removed, the false-negative rate of SLN biopsy (SLNB) was relatively low, 12.6%. Therefore, the role of axillary imaging in NAC setting should be to find out metastatic lymph nodes (LNs) for surgeons to proceed directly to ALND. Another role could be to correctly diagnose negative LN to safely omit SLNB. Despite the importance of restaging of nodal status, there have been few studies about diagnostic accuracy of imaging modalities for detection of metastatic ALNs after NAC.The purpose of our study was to evaluate the diagnostic performance of ultrasound, MRI and fluorine-18 fludeoxyglucose positron emission tomography (¹⁸F-FDG PET)/CT for the diagnosis of metastatic ALNs after NAC and to find out histopathological factors affecting the diagnostic accuracy of these imaging modalities.     

Diagnostic value of diffusion-weighted magnetic resonance imaging (DWI) compared to FDG PET/CT for whole-body breast cancer staging

Purpose

The aim of the study was to prospectively compare the diagnostic value of whole-body diffusion-weighted imaging (DWI) and FDG PET/CT for breast cancer (BC) staging.

Methods

Twenty BC patients underwent whole-body FDG PET/CT and 1.5-T DWI. Lesions with qualitatively elevated signal intensity on DW images (b?=?800 s/mm²) were rated as suspicious for tumour and mapped to individual lesions and different compartments (overall 552 lesions). The apparent diffusion coefficient (ADC) value was determined for quantitative evaluation. Histopathology, MRI findings, bone scan findings, concordant findings between FDG PET/CT and DWI, CT follow-up scans and plausibility served as the standards of reference defining malignancy.

Results

According to the standards of reference, breasts harboured malignancy in 11, regional lymph nodes in 4, M1 lymph nodes in 3, bone in 7, lung in 2, liver in 3 and other tissues in 3 patients. On a compartment basis, the sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) for the detection of malignancies were 94, 99, 98, 97 and 98% for FDG PET/CT and 91, 72, 76, 50 and 96% for DWI, respectively. Of the lesions seen on DWI only, 348 (82%) turned out to be false-positive compared to 23 (11%) on FDG PET/CT. The average lesion ADC was 820?±?300 with true-positive lesions having 929?±?252 vs 713?±?305 in false-positive lesions (p?<?0.0001).

Conclusion

Based on these initial data DWI seems to be a sensitive but unspecific modality for the detection of locoregional or metastatic BC disease. There was no possibility to quantitatively distinguish lesions using ADC. DWI alone may not be recommended as a whole-body staging alternative to FDG PET(/CT). Further studies are necessary addressing the question of whether full-body MRI including DWI may become an alternative to FDG PET/CT for whole-body breast cancer staging.     

Comparison of whole-body PET/CT and PET/MRI in breast cancer patients: Lesion detection and quantitation of 18F-deoxyglucose uptake in lesions and in normal organ tissues

Purpose

To compare the performance of PET/MRI imaging using MR attenuation correction (MRAC) (DIXON-based 4-segment -map) in breast cancer patients with that of PET/CT using CT-based attenuation correction and to compare the quantification accuracy in lesions and in normal organ tissues.

Methods

A total of 36 patients underwent a whole-body PET/CT scan 1 h after injection and an average of 62 min later a second scan using a hybrid PET/MRI system. PET/MRI and PET/CT were compared visually by rating anatomic allocation and image contrast. Regional tracer uptake in lesions was quantified using volumes of interest, and maximal and mean standardized uptake values (SUVmax and SUVmean, respectively) were calculated. Metabolic tumor volume (MTV) of each lesion was computed on PET/MRI and PET/CT. Tracer uptake in normal organ tissue was assessed as SUVmax and SUVmean in liver, spleen, left ventricular myocardium, lung, and muscle.

Results

Overall 74 FDG positive lesions were visualized by both PET/CT and PET/MRI. No significant differences in anatomic allocation scores were found between PET/CT and PERT/MRI, while contrast score of lesions on PET/MRI was significantly higher. Both SUVmax and SUVmean of lesions were significantly higher on PET/MRI than on PET/CT, with strong correlations between PET/MRI and PET/CT data (ρ = 0.71–0.88). MTVs of all lesions were 4% lower on PET/MRI than on PET/CT, but no statistically significant difference was observed, and an excellent correlation between measurements of MTV with PET/MRI and PET/CT was found (ρ = 0.95–0.97; p < 0.0001). Both SUVmax and SUVmean were significantly lower by PET/MRI than by PET/CT for lung, liver and muscle, no significant difference was observed for spleen, while either SUVmax and SUVmean of myocardium were significantly higher by PET/MRI. High correlations were found between PET/MRI and PET/CT for both SUVmax and SUVmean of the left ventricular myocardium (ρ = 0.91; p < 0.0001), while moderate correlations were found for the other normal organ tissues (ρ = 0.36–0.61; p < 0.05).

Conclusions

PET/MRI showed equivalent performance in terms of qualitative lesion detection to PET/CT. Despite significant differences in tracer uptake quantification, due to either methodological and biological factors, PET/MRI and PET/CT measurements in lesions and normal organ tissues correlated well. This study demonstrates that integrated whole-body PET/MRI is feasible in a clinical setting with high quality and in a short examination time.     

Feasibility of perfusion CT technique integrated into conventional 18FDG/PET-CT studies in lung cancer patients: clinical staging and functional information in a single study

Purpose

To assess the additional functional vascular information and the relationship between perfusion measurements and glucose metabolism (SUVmax) obtained by including a perfusion CT study in a whole-body contrast-enhanced PET/CT protocol in primary lung cancer lesions.

Methods

Enrolled in this prospective study were 34 consecutive patients with a biopsy-proven diagnosis of lung cancer who were referred for contrast-enhanced PET/CT staging. This prospective study was approved by our institutional review board, and informed consent was obtained from all patients. Perfusion CT was performed with the following parameters: 80 kV, 200 mAs, 30 scans during intravenous injection of 50 ml contrast agent, flow rate 5 ml/s. Another bolus of contrast medium (3.5 ml/s, 80 ml, 60-s delay) was administered to ensure a full diagnostic contrast-enhanced CT scan for clinical staging. The perfusion CT data were used to calculate a range of tumour vascularity parameters (blood flow, blood volume and mean transit time), and tumour FDG uptake (SUVmax) was used as a metabolic indicator. Quantitative and functional parameters were compared and in relation to location, histology and tumour size. The nonparametric Kruskal-Wallis rank sum test was used for statistical analysis.

Results

A cut-off value of 3 cm was used according to the TNM classification to discriminate between T1 and T2 tumours (i.e. T1b vs. T2a). There were significant perfusion differences (lower blood volumes and higher mean transit time) between tumours with diameter >30 mm and tumours with diameter <30 mm (p?<?0.05; blood volume 5.6 vs. 7.1 ml/100 g, mean transit time 8.6 vs. 3.9 s, respectively). Also there was a trend for blood flow to be lower in larger lesions (p?<?0.053; blood flow 153.1 vs. 98.3 ml/100 g tissue/min). Significant inverse correlations (linear regression) were found between blood volume and SUVmax in tumours with diameter >30 mm in diameter.

Conclusion

Perfusion CT combined with PET/CT is feasible technique that may provide additional functional information about vascularity and tumour aggressiveness as a result of lower perfusion and higher metabolism shown by larger lesions.     

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 increment in standardized uptake value determined using dual-phase 18F-FDG PET is a promising prognostic factor in non-small-cell lung cancer

Purpose

We aimed to determine whether the increment in the maximal standardized uptake value (SUVmax) of the primary lung tumour between the initial and delayed imaging by dual-phase ¹⁸F-FDG PET has prognostic value in patients with non-small-cell lung cancer (NSCLC).

Methods

We reviewed the records of patients with NSCLC who underwent pretreatment dual-phase ¹⁸F-FDG PET/CT scans acquired at 1 h and 2 h after injection. The SUVmax increment (SUVinc) of the primary lung tumour was the 2-h SUVmax minus the 1-h SUVmax. Univariate and multivariate analyses were used to assess the prognostic significance of SUVinc, retention index, whole-body total metabolic tumour volume, whole-body total lesion glycolysis (TLGwb), 1-h SUVmax, 2-h SUVmax, gender, age, performance status, histological subtype, T stage, N stage and clinical stage.

Results

The records of 187 consecutive patients were reviewed. The median follow-up time was 3.9 years. The estimated median progression-free survival (PFS) and overall survival (OS) were 1.3 years and 4.4 years, respectively. An SUVinc cut-off value of >1 had the best discriminative yield for PFS. The 3-year PFS and OS were 61.6 % and 87.8 % in patients with SUVinc ≤1 versus 21.1 % and 46.2 % in patients with SUVinc >1 (all P?<?0.01). Using the forward stepwise multivariate Cox proportional hazards model, SUVinc, TLGwb, and clinical stage were significant factors for PFS (all P?<?0.01). A subgroup analysis of 117 patients treated with surgery showed that SUVinc (P?=?0.02) and clinical stage (P?<?0.01) were significant prognostic factors for PFS. Furthermore, in stage I patients treated with surgery alone, SUVinc was the only significant prognostic factor (HR 28.07; 95 % CI 2.42 – 326.41).

Conclusion

SUVinc determined from dual-phase ¹⁸F-FDG PET is a promising prognostic factor for NSCLC. It adds to the value of dual-phase ¹⁸F-FDG PET.     

The value of 18F-FDG PET/CT in the assessment of active idiopathic retroperitoneal fibrosis

Purpose

The different stages in idiopathic retroperitoneal fibrosis (IRF) are generally assessed by assay of inflammatory markers and analysis of contrast-enhanced CT images of the retroperitoneal mass. We investigated the potential role of ¹⁸F-FDG PET/CT in this clinical setting.

Methods

¹⁸F-FDG uptake was assessed visually and semiquantitatively (using maximum standardized uptake values, SUVmax) in images of the abdominal mass in 22 patients prospectively enrolled from June 2008 to December 2010 who underwent a total of 33 PET/CT studies. The accuracy in discriminating active from inactive disease was calculated assuming as reference a biochemical instrumental evaluation of patients with IRF mostly based on the level of inflammatory indices and contrast enhancement (CE) of the mass at the time of each PET study. In particular, the relationship between SUVmax and CE, the latter calculated from the change in radiodensity (Hounsfield units) between the basal and postcontrast venous portal phases, was evaluated on a three-point scale (0 <20?HU, 1 20–30?HU, 2 ≥30?HU). SUVmax and CE scores were correlated with the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. The value of PET/CT in assessing the variation of disease activity over time was also investigated by analysing the changes in metabolic volume (MV) of the retroperitoneal lesion between repeat patient studies.

Results

PET/CT accurately discriminated (93.9?%) active from inactive disease. Significant agreement (p?<?0.01) was observed between visual and semiquantitative analysis of ¹⁸F-FDG uptake, and CE score. A significant correlation (p?<?0.01) was found among SUVmax, CRP levels (rho?=?0.54) and ESR (rho?=?0.55). Corresponding variations in MV and CE score were observed in patients with multiple studies (p?<?0.01; rho?=?0.68).

Conclusion

¹⁸F-FDG PET/CT may be considered an alternative imaging method for the assessment of different stages of IRF.     

PET-based delineation of tumour volumes in lung cancer: comparison with pathological findings

Purpose

The objective of the study was to validate an adaptive, contrast-oriented thresholding algorithm (COA) for tumour delineation in ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for non-small cell lung cancer (NSCLC) in comparison with pathological findings. The impact of tumour localization, tumour size and uptake heterogeneity on PET delineation results was also investigated.

Methods

PET tumour delineation by COA was compared with both CT delineation and pathological findings in 15 patients to investigate its validity. Correlations between anatomical volume, metabolic volume and the pathology reference as well as between the corresponding maximal diameters were determined. Differences between PET delineations and pathological results were investigated with respect to tumour localization and uptake heterogeneity.

Results

The delineated volumes and maximal diameters measured on PET and CT images significantly correlated with the pathology reference (both r?>?0.95, p?<?0.0001). Both PET and CT contours resulted in overestimation of the pathological volume (PET 32.5?±?26.5 %, CT 46.6?±?27.4 %). CT volumes were larger than those delineated on PET images (CT 60.6?±?86.3 ml, PET 48.3?±?61.7 ml). Maximal tumour diameters were similar for PET and CT (51.4?±?19.8 mm for CT versus 53.4?±?19.1 mm for PET), slightly overestimating the pathological reference (mean difference CT 4.3?±?3.2 mm, PET 6.2?±?5.1 mm). PET volumes of lung tumours located in the lower lobe were significantly different from those determined from pathology (p?=?0.037), whereas no significant differences were observed for tumours located in the upper lobe (p?=?0.066). Only minor correlation was found between pathological tumour size and PET heterogeneity (r?=??0.24).

Conclusion

PET tumour delineation by COA showed a good correlation with pathological findings. Tumour localization had an influence on PET delineation results. The impact of tracer uptake heterogeneity on PET delineation should be considered carefully and individually in each patient. Altogether, PET tumour delineation by COA for NSCLC patients is feasible and reliable with the potential for routine clinical application.     

Simultaneous whole-body and breast 18F-FDG PET/MRI examinations in patients with breast cancer: a comparison of apparent diffusion coefficients and maximum standardized uptake values

Purpose

To compare standardized uptake value (SUV) and apparent diffusion coefficient (ADC) values acquired using a PET/MRI scanner in breast cancer patients.

Materials and methods

Whole-body PET/MRI and breast PET/MRI were performed in 108 consecutive patients. Ninety-four patients who had a total of 100 breast cancers were analyzed. SUVmax and ADCmean acquired using breast PET/MRI were compared with pathologic prognostic factors.

Results

All the lesions were visually detectable using PET and diffusion-weighted imaging (DWI) on breast PET/MRI; however, lesions were visually undetectable on whole-body DWI in 13 patients (13%) or on whole-body PET in 7 patients (7%). An analysis of ADCmean and SUVmax demonstrated a statistically significant correlation between whole-body imaging and breast imaging (rho = 0.613, p < 0.001 and rho = 0.928, p < 0.001, respectively). In a univariate analysis, SUVmax was significantly correlated with HER2 status (p < 0.001), Ki-67 (p = 0.014), tumor size (p = 0.0177), and nuclear grade (p = 0.0448). In multiple regression analysis, only tumor size (p = 0.00701) was shown to independently influence SUVmax.

Conclusion

Prone breast imaging was more sensitive than whole-body PET/MRI for detection of breast cancers. Both SUVmax and ADCmean showed limited correlation with pathologic prognostic factors.