Correlation of breast cancer subtypes,based on estrogen receptor,progesterone receptor,and HER2, with functional imaging parameters from 68Ga-RGD PET/CT and 18F-FDG PET/CT

Purpose

Imaging biomarkers from functional imaging modalities were assessed as potential surrogate markers of disease status. Specifically, in this prospective study, we investigated the relationships between functional imaging parameters and histological prognostic factors and breast cancer subtypes.

Methods

In total, 43 patients with large or locally advanced invasive ductal carcinoma (IDC) were analyzed (47.6?±?7.5 years old). ⁶⁸Ga-Labeled arginine-glycine-aspartic acid (RGD) and ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) were performed. The maximum and average standardized uptake values (SUV_max and SUV_avg) from RGD PET/CT and SUV_max and SUV_avg from FDG PET/CT were the imaging parameters used. For histological prognostic factors, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression was identified using immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH). Four breast cancer subtypes, based on ER/PR and HER2 expression (ER/PR+,Her2?, ER/PR+,Her2+, ER/PR?,Her2+, and ER/PR?,Her2?), were considered.

Results

Quantitative FDG PET parameters were significantly higher in the ER-negative group (15.88?±?8.73 vs 10.48?±?6.01, p?=?0.02 for SUV_max; 9.40?±?5.19 vs 5.92?±?4.09, p?=?0.02 for SUV_avg) and the PR-negative group (8.37?±?4.94 vs 4.79?±?3.93, p?=?0.03 for SUV_avg). Quantitative RGD PET parameters were significantly higher in the HER2-positive group (2.42?±?0.59 vs 2.90?±?0.75, p?=?0.04 for SUV_max; 1.60?±?0.38 vs 1.95?±?0.53, p?=?0.04 for SUV_avg) and showed a significant positive correlation with the HER2/CEP17 ratio (r?=?0.38, p?=?0.03 for SUV_max and r?=?0.46, p?<?0.01 for SUV_avg). FDG PET parameters showed significantly higher values in the ER/PR?,Her2? subgroup versus the ER/PR+,Her2? or ER/PR+,Her2+ subgroups, while RGD PET parameters showed significantly lower values in the ER/PR?,Her2? subgroup versus the other subgroups. There was no correlation between FDG and RGD PET parameters in the overall group. Only the ER/PR?,Her2? subgroup showed a significant positive correlation between FDG and RGD PET parameters (r?=?0.59, p?=?0.03 for SUV_max).

Conclusion

⁶⁸Ga-RGD and ¹⁸F-FDG PET/CT are promising functional imaging modalities for predicting biomarkers and molecular phenotypes in breast cancer patients.     

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.     

68Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT

Purpose

We wanted to establish the range of ⁶⁸Ga-DOTA-TOC uptake in liver and bone metastases of patients with neuroendocrine tumours (NET) and to establish the range of its uptake in pancreatic NET. This would allow differentiation between physiological uptake and tumour-related somatostatin receptor expression in the pancreas (including the uncinate process), liver and bone. Finally, we wanted to test for differences in patients with NET, either treated or not treated with peptide receptor radionuclide therapy (PRRT).

Methods

In 249 patients, 390 ⁶⁸Ga-DOTA-TOC PET/CT studies were performed. The clinical indications for PET/CT were gastroenteropancreatic NET (194 studies), nongastroenteropancreatic NET (origin in the lung and rectum; 46 studies), NET of unknown primary (111 studies), phaeochromocytoma/glomus tumours (18 studies), and radioiodine-negative metastatic thyroid carcinoma (21 studies).

Results

SUV_max (mean ± standard deviation) values of ⁶⁸Ga-DOTA-TOC were 29.8?±?16.5 in 162 liver metastases, 19.8?±?18.8 in 89 bone metastases and 34.6?±?17.1 in 43 pancreatic NET (33.6?±?14.3 in 30 tumours of the uncinate process and 36.3?±?21.5 in 13 tumours of the pancreatic tail). A significant difference in SUV_max (p?<?0.02) was found in liver metastases of NET patients treated with PRRT. There were significant differences in SUV_max between nonmalignant and malignant tissue for both bone and liver metastases and for pancreatic NET including the uncinate process (p?<?0.0001). At a cut-off value of 17.1 the specificity and sensitivity of SUV_max for differentiating tumours in the uncinate process were 93.6 % and 90.0 %, respectively (p?<?0.0001).

Conclusion

⁶⁸Ga-DOTA-TOC is an excellent tracer for the imaging of tumours expressing somatostatin receptors on the tumour cell surface, facilitating the detection of even small tumour lesions. The noninvasive PET/CT approach by measurement of regional SUV_max can offer important clinical information to distinguish between physiological and pathological somatostatin receptor expression, especially in the uncinate process. PRRT does not significantly influence SUV_max, except in liver metastases of patients with NET.     

Diffusion-weighted MRI in pretreatment prediction of response to neoadjuvant chemotherapy in patients with breast cancer

Purpose

To evaluate the accuracy of the apparent diffusion coefficient (ADC) provided by diffusion-weighted imaging (DWI) in predicting the response to neoadjuvant chemotherapy (NACT) at baseline in patients according to their breast tumour phenotypes.

Materials & methods

This retrospective study was approved by our institutional review board. One hundred eighteen consecutive women with locally advanced breast cancer who had undergone NACT followed by breast surgery were included. DWI was performed at 1.5 T less than 2 weeks before NACT. We studied the correlation between pretreatment ADC and response in pathology after surgery according to immunohistochemical features and intrinsic subtypes (luminal A, luminal B, HER2-enriched, and triple-negative tumours).

Results

After surgery, the pathologist recognized 24 complete responders (CRps) and 94 non-complete responders (NCRps). No difference was identified between the pretreatment ADCs of the CRp and NCRp patients. There were differences in pretreatment ADCs among the luminal A (1.001 ± 0.143?×?10^?3 mm²/s), luminal B (0.983 ± 0.150?×?10^?3 mm²/s), HER2-enriched (1.132 ± 0.216?×?10^?3 mm²/s), and triple-negative (1.168 ± 0.245?×?10^?3 mm²/s; P?=?0.0003) tumour subtypes. In triple-negative tumours, the pretreatment ADC was higher in NCRp (1.060 ± 0.143?×?10^?3 mm²/s) than in CRp patients (1.227 ± 0.271?×?10^?3 mm²/s; P?=?0.047).

Conclusion

Pretreatment ADC can predict the response of breast cancer to NACT if tumour subtypes are considered. Key Points ? Apparent diffusion coefficient helps clinicians to assess patients with breast cancer. ? Pretreatment ADC is related to tumour grade and hormone receptor status. ? Pretreatment ADC is lower in luminal A and B than in triple-negative tumours. ? Pretreatment ADC is higher in complete than in non-complete responders to neoadjuvant chemotherapy.     

Suppression of myocardial 18F-FDG uptake with a preparatory “Atkins-style” low-carbohydrate diet

Objectives

Physiological myocardial uptake of 18F-FDG during positron emission tomography can mask adjacent abnormal uptake in mediastinal malignancy and inflammatory cardiac diseases. Myocardial uptake is unpredictable and variable. This study evaluates the impact of a low-carbohydrate diet in reducing myocardial FDG uptake.

Method

Patients attending for clinically indicated oncological FDG PET were asked to have an “Atkins-style” low-carbohydrate diet (less than 3 g) the day before examination and an overnight fast. A total of 120 patients following low-carbohydrate diet plus overnight fast were compared with 120 patients prepared by overnight fast alone. Patients having an Atkins-style diet also completed a diet compliance questionnaire. SUV_max and SUV_mean for myocardium, blood pool and liver were measured in both groups.

Results

Myocardial SUV_max fell from 3.53?±?2.91 in controls to 1.77?±?0.91 in the diet-compliant group. 98 % of diet-compliant patients had a myocardial SUV_max less than 3.6 compared with 67 % of controls. Liver and blood pool SUV_max rose from 2.68?±?0.49 and 1.82?±?0.30 in the control group to 3.14?±?0.57 and 2.06?±?0.30.

Conclusion

An Atkins-style diet the day before PET, together with an overnight fast, effectively suppresses myocardial FDG uptake.

Key Points

? Low-carbohydrate diet (LCD) the day before PET suppresses myocardial FDG uptake. ? LCD before PET increases liver and blood pool SUV _max and SUV _mean . ? Suppression of myocardial uptake may improve PET imaging of thoracic disease. ? Suppression of myocardial uptake may help imaging cardiac inflammatory disease with PET.     

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.     

Detection of unknown primary neuroendocrine tumours (CUP-NET) using 68Ga-DOTA-NOC receptor PET/CT

Purpose

This bi-centric study aimed to determine the role of receptor PET/CT using ⁶⁸Ga-DOTA-NOC in the detection of undiagnosed primary sites of neuroendocrine tumours (NETs) and to understand the molecular behaviour of the primarily undiagnosed tumours.

Methods

Overall 59 patients (33 men and 26 women, age: 65?±?9 years) with documented NET and unknown primary were enrolled. PET/CT was performed after injection of approximately 100 MBq (46–260 MBq) of ⁶⁸Ga-DOTA-NOC. The maximum standardised uptake values (SUV_max) were calculated and compared with SUV_max in known pancreatic NET (pNET) and ileum/jejunum/duodenum (SI-NET). The results of PET/CT were also correlated with CT alone.

Results

In 35 of 59 patients (59%), ⁶⁸Ga-DOTA-NOC PET/CT localised the site of the primary: ileum/jejunum (14), pancreas (16), rectum/colon (2), lungs (2) and paraganglioma (1). CT alone (on retrospective analyses) confirmed the findings in 12 of 59 patients (20%). The mean SUV_max of identified previously unknown pNET and SI-NET were 18.6?±?9.8 (range: 7.8–34.8) and 9.1?±?6.0 (range: 4.2–27.8), respectively. SUV_max in patients with previously known pNET and SI-NET were 26.1?±?14.5 (range: 8.7–42.4) and 11.3?±?3.7 (range: 5.6–17.9). The SUV_max of the unknown pNET and SI-NET were significantly lower (p?<?0.05) as compared to the ones with known primary tumour sites; 19% of the patients had high-grade and 81% low-grade NET. Based on ⁶⁸Ga-DOTA-NOC receptor PET/CT, 6 of 59 patients were operated and the primary was removed (4 pancreatic, 1 ileal and 1 rectal tumour) resulting in a management change in approximately 10% of the patients. In the remaining 29 patients, because of the far advanced stage of the disease (due to distant metastases), the primary tumours were not operated. Additional histopathological sampling was available from one patient with bronchial carcinoid (through bronchoscopy).

Conclusion

Our data indicate that ⁶⁸Ga-DOTA-NOC PET/CT is highly superior to ¹¹¹In-OctreoScan (39% detection rate for CUP according to the literature) and can play a major role in the management of patients with CUP-NET.     

Assessment of aortitis by semiquantitative analysis of 180-min 18F-FDG PET/CT acquisition images

Purpose

The aim of this study was to evaluate the contribution of semiquantitative analysis of 180-min ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT images for the assessment of aortitis in cases of suspected large vessel vasculitis (LVV) and to establish a threshold index for application in the clinical setting.

Methods

This prospective study included 43 patients (mean age 67.5?±?12.9?years) with suspicion of LVV (25 with a final diagnosis of aortitis). ¹⁸F-FDG PET/CT scan was acquired 180 min after injection of 7 MBq/kg of ¹⁸F-FDG. A semiquantitative analysis was performed calculating the aortic wall maximum standardized uptake value (SUV_max) (T), the lumen SUV_max (B) and the target to background ratio (TBR). These results were also compared with those obtained in a control population.

Results

The mean aortic wall SUV_max was 2.00?±?0.62 for patients with aortitis and 1.45?±?0.31 for patients without aortitis (p?p?max (0.997 vs 0.871). The highest sensitivity and specificity was obtained for a TBR of 1.34 (sensitivity 100 %, specificity 94.4 %).

Conclusion

Semiquantitative analysis of PET/CT images acquired 180 min after ¹⁸F-FDG injection and the TBR index of 1.34 show very high accuracy and, therefore, are strongly recommended for the diagnosis of aortitis in the clinical setting.     

Twins in spirit part II: DOTATATE and high-affinity DOTATATE—the clinical experience

Purpose

Over recent decades interest in diagnosis and treatment of neuroendocrine tumours (NET) has steadily grown. The basis for diagnosis and therapy of NET with radiolabelled somatostatin (hsst) analogues is the variable overexpression of hsst receptors (hsst1–5 receptors). We hypothesized that radiometal derivatives of DOTA-iodo-Tyr³-octreotide analogues might be excellent candidates for somatostatin receptor imaging. We therefore explored the diagnostic potential of ⁶⁸Ga-DOTA-iodo-Tyr³-octreotate [⁶⁸Ga-DOTA,3-iodo-Tyr³,Thr⁸]octreotide (⁶⁸Ga-HA-DOTATATE; HA, high-affinity) compared to the established ⁶⁸Ga-DOTA-Tyr³-octreotate (⁶⁸Ga-DOTATATE) in vivo.

Methods

The study included 23 patients with known somatostatin receptor-positive metastases from NETs, thyroid cancer or glomus tumours who were investigated with both ⁶⁸Ga-HA-DOTATATE and ⁶⁸Ga-DOTATATE. A patient-based and a lesion-based comparative analysis was carried out of normal tissue distribution and lesion detectability in a qualitative and a semiquantitative manner.

Results

⁶⁸Ga-HA-DOTATATE and ⁶⁸Ga-DOTATATE showed comparable uptake in the liver (SUV_mean 8.9?±?2.2 vs. 9.3?±?2.5, n.s.), renal cortex (SUV_mean 13.3?±?3.9 vs. 14.5?±?3.7, n.s.) and spleen (SUV_mean 24.0?±?6.7 vs. 22.9?±?7.3, n.s.). A somewhat higher pituitary uptake was found with ⁶⁸Ga-HA-DOTATATE (SUV_mean 6.3?±?1.8 vs. 5.4?±?2.1, p?<?0.05). On a lesion-by-lesion basis a total of 344 lesions were detected. ⁶⁸Ga-HA-DOTATATE demonstrated 328 lesions (95.3 % of total lesions seen), and ⁶⁸Ga-DOTATATE demonstrated 332 lesions (96.4 %). The mean SUV_max of all lesions was not significantly different between ⁶⁸Ga-HA-DOTATATE and ⁶⁸Ga-DOTATATE (17.8?±?11.4 vs. 16.7?±?10.7, n.s.).

Conclusion

Our analysis demonstrated very good concordance between ⁶⁸Ga-HA-DOTATATE and ⁶⁸Ga-DOTATATE PET data. As the availability and use of ⁶⁸Ga-HA-DOTATATE is not governed by patent restrictions it may be an attractive alternative to other ⁶⁸Ga-labelled hsst analogues.     

Quantitative evaluation of bone metastases from prostate cancer with simultaneous [18F] choline PET/MRI: combined SUV and ADC analysis

Objective

To quantitatively analyze bone metastases from prostate cancer and correlate the apparent diffusion coefficients (ADCs) and standardized uptake values (SUVs).

Methods

Fifty-five patients with biopsy-proven prostate cancer or suspected recurrent prostate cancer were examined with simultaneous [¹⁸F] choline Positron emission tomography (PET)/MRI at 3 T. In 11 patients, thirty-two PET-positive bone lesions could be identified that were located in the field-of-view of the Diffusion weighted imaging-sequence. Region-of-interest and volume-of-interest analyses were performed to measure the mean and minimal ADCs and to assess maximum and mean SUVs of every bone lesion. Correlations between maximum and mean SUVs and mean and minimal ADCs were calculated.

Results

The SUV_max of all lesions was 5.5 ± 3.1 (mean ± SD). The SUV_mean was 1.8 ± 0.9. The mean ADC (ADC_mean) of all lesions was 0.67 ± 0.13 × 10^?3 mm²/s. The minimal ADC (ADC_min) of all lesions was 0.56 ± 0.14 × 10^?3 mm²/s. There was a moderate but significant inverse correlation of SUV_max vs. ADC_mean with a correlation coefficient of ?0.4 (p = 0.02). There was also a significant inverse correlation of SUV_max vs. ADC_min with r = ?0.41 (p = 0.02).

Conclusion

Our initial results demonstrate a moderate but significant inverse correlation between increased choline metabolism and ADC values of bone metastases from prostate cancer. Further research on a multimodality approach using simultaneous PET/MRI in bone metastasis of prostate cancer seems to be justified.     

Tumour volume doubling time of molecular breast cancer subtypes assessed by serial breast ultrasound

Objectives

The aim of our study was to evaluate the tumour volume doubling time (TVDT) of molecular breast cancer subtypes by serial ultrasound (US).

Methods

Sixty-six patients (mean age, 50 years; range, 29–78 years) with invasive breast cancer underwent initial and follow-up breast US examinations (at least three months apart) with no intervention. TVDT was determined using the tumours’ greatest dimensions in two orthogonal planes. The results were compared with clinical, imaging, and tumour variables and molecular subtypes (oestrogen receptor [ER]-positive, human epidermal growth factor receptor 2 [HER2]-positive, and triple negative) using a multiple linear regression analysis.

Results

TVDT exhibited a wide range (46–825 days; median, 141 days) with an overall mean of 193?±?141 days and mean values of 241?±?166 days for ER-positive tumours (n?=?37), 162?±?60 days for HER2-positive tumours (n?=?12), and 103?±?43 days for triple-negative tumours (n?=?17) (P?P?Conclusions TVDT differed significantly among the three molecular breast cancer subtypes, with the triple-negative tumours showing the fastest growth.

Key Points

? Knowledge of tumour volume doubling time provides clues for improving screening. ? TVDT assessed by serial US differed significantly between breast cancer subtypes. ? Triple-negative tumours had 2.4-fold shorter TVDT compared to ER-positive tumours. ? Tumours classified as BI-RADS 3 had shorter TVDT than BI-RADS 4.     

PET SUV correlates with radionuclide uptake in peptide receptor therapy in meningioma

Purpose

To investigate whether the tumour uptake of radionuclide in peptide receptor radionuclide therapy (PRRT) of meningioma can be predicted by a PET scan with ⁶⁸Ga-labelled somatostatin analogue.

Methods

In this pilot trial, 11 meningioma patients with a PET scan indicating somatostatin receptor expression received PRRT with 7.4?GBq ¹⁷⁷Lu-DOTATOC or ¹⁷⁷Lu-DOTATATE, followed by external beam radiotherapy. A second PET scan was scheduled for 3?months after therapy. During PRRT, multiple whole-body scans and a SPECT/CT scan of the head and neck region were acquired and used to determine the kinetics and dose in the voxel with the highest radionuclide uptake within the tumour. Maximum voxel dose and retention of activity 1?h after administration in PRRT were compared to the maximum standardized uptake values (SUV_max) in the meningiomas from the PET scans before and after therapy.

Results

The median SUV_max in the meningiomas was 13.7 (range 4.3 to 68.7), and the maximum fractional radionuclide uptake in voxels of size 0.11?cm3 was a median of 23.4?×?10^?6 (range 0.4?×?10^?6 to 68.3?×?10^?6). A strong correlation was observed between SUV_max and the PRRT radionuclide tumour retention in the voxels with the highest uptake (Spearman’s rank test, P?max and the therapeutic uptake (r?=?0.95) and between SUV_max and the maximum voxel dose from PRRT (r?=?0.76). Observed absolute deviations from the values expected from regression were a median of 5.6?×?10^?6 (maximum 9.3?×?10^?6) for the voxel fractional radionuclide uptake and 0.40?Gy per GBq (maximum 0.85?Gy per GBq) ¹⁷⁷Lu for the voxel dose from PRRT.

Conclusion

PET with ⁶⁸Ga-labelled somatostatin analogues allows the pretherapeutic assessment of tumour radionuclide uptake in PRRT of meningioma and an estimate of the achievable dose.     

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.     

Prognostic relevance of 18F-FDG PET uptake in patients with locally advanced,extremity soft tissue sarcomas undergoing neoadjuvant isolated limb perfusion with TNF-α and melphalan

Purpose

The objective of this study was to determine whether ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) can adequately assess the risk of systemic disease progression in patients with primary, localized, high-grade soft tissue sarcomas of the extremities undergoing neoadjuvant isolated limb perfusion (ILP) with tumour necrosis factor and melphalan.

Methods

This was a retrospective analysis of the files of 35 patients who underwent a PET or PET/CT scan prior to and after ILP followed by surgical resection with curative intent between 2006 and 2012. SUV_max1 was defined as the maximum standardized uptake value (SUV) at diagnosis, SUV_max2 as the maximum SUV after ILP and ΔSUV_max as the percentage difference between SUV_max1 and SUV_max2.

Results

The median follow-up was 40 months for all patients. The median SUV_max1 amounted to 7.6, while the median SUV_max2 was 4.7. The median ΔSUV_max was ?44 %. Overall survival (OS) probability at 2 and 5 years amounted to 78 and 70 %, respectively, while metastasis-free survival (MFS) probability at 2 and 5 years was 67 and 64 %, respectively. Receiver-operating characteristic (ROC) curve analysis showed that both SUV_max2 and ΔSUV_max could predict systemic disease progression, while SUV_max1 could not adequately identify patients who went on to develop metastatic disease. The optimal cut-off value was 6.9 for SUV_max2 and ?31 % for ΔSUV_max. Patients with an SUV_max2 <6.9 had a 2-year MFS of 80 %, compared to 31 % for patients with an SUV_max2?≥?6.9 (p?<?0.001). Patients with a ΔSUV_max?<??31 %, i.e. patients with a higher metabolic response, had an MFS of 76 % at 2 years, compared to 42 % for patients with a ΔSUV_max?≥??31 % (p?=?0.050).

Conclusion

SUV_max after ILP for primary, locally advanced, non-metastatic high-grade soft tissue sarcomas of the extremities appears to be significantly correlated with prognosis. Whether patients with a high SUV_max after ILP will benefit from standard or experimental adjuvant systemic treatment options should be evaluated in future studies.     

[18F]Fluciclatide in the in vivo evaluation of human melanoma and renal tumors expressing αvβ3 and αvβ5 integrins

Purpose

[¹⁸F]Fluciclatide is an integrin-targeted PET radiopharmaceutical. α_vβ₃ and α_vβ₅ are upregulated in tumor angiogenesis as well as on some tumor cell surfaces. Our aim was to use [¹⁸F]fluciclatide (formerly known as [¹⁸F]AH111585) for PET imaging of angiogenesis in melanoma and renal tumors and compare with tumor integrin expression.

Methods

Eighteen evaluable patients with solid tumors ≥2.0 cm underwent [¹⁸F]fluciclatide PET/CT. All patients underwent surgery and tumor tissue samples were obtained. Immunohistochemical (IHC) staining with mouse monoclonal antibodies and diaminobenzidine (DAB) was applied to snap-frozen tumor specimens, and additional IHC was done on formalin-fixed paraffin-embedded samples. DAB optical density (OD) data from digitized whole-tissue sections were compared with PET SUV_{80% max}, and Patlak influx rate constant (K _i) data, tumor by tumor.

Results

Tumors from all 18 patients demonstrated measurable [¹⁸F]fluciclatide uptake. At the final dynamic time-point (55 min after injection), renal malignancies (in 11 patients) demonstrated an average SUV_{80% max} of 6.4?±?2.0 (range 3.8 – 10.0), while the average SUV_{80% max} for metastatic melanoma lesions (in 6 patients) was 3.0?±?2.0 (range 0.7 – 6.5). There was a statistically significant difference in [¹⁸F]fluciclatide uptake between chromophobe and nonchromophobe renal cell carcinoma (RCCs, with SUV_{80% max} of 8.2?±?1.8 and 5.4?±?1.4 (P?=?0.020) and tumor-to-normal kidney (T/N) ratios of 1.5?±?0.4 and 0.9?±?0.2, respectively (P?=?0.029). The highest Pearson's correlation coefficients were obtained when comparing Patlak K _i and α_vβ₅ OD when segregating the patient population between melanoma and RCC (r?=?0.83 for K _i vs. melanoma and r?=?0.91 for K _i vs. RCC). SUV_{80% max} showed a moderate correlation with α_vβ₅ and α_vβ₃ OD.

Conclusion

[¹⁸F]Fluciclatide PET imaging was well tolerated and demonstrated favorable characteristics for imaging α_vβ₃ and α_vβ₅ expression in melanoma and RCC. Higher uptake was observed in chromophobe than in nonchromophobe RCC. [¹⁸F]Fluciclatide may be a useful radiotracer to improve knowledge of integrin expression.     

Functional imaging of head and neck squamous cell carcinoma with diffusion-weighted MRI and FDG PET/CT: quantitative analysis of ADC and SUV

Purpose

Head and neck squamous cell carcinoma (HNSCC) may cause a decreased apparent diffusion coefficient (ADC) on diffusion-weighted magnetic resonance imaging (DW MRI) and an increased standardized uptake value (SUV) on fluorodeoxyglucose (FDG) positron emission tomography (PET/CT). We analysed the reproducibility of ADC and SUV measurements in HNSCC and evaluated whether these biomarkers are correlated or independent.

Methods

This retrospective analysis of DW MRI and FDG PET/CT data series included 34 HNSCC in 33 consecutive patients. Two experienced readers measured tumour ADC and SUV values independently. Statistical comparison and correlation with histopathology was done. Intra- and inter-observer agreement for ADC and SUV measurements was assessed.

Results

Intraclass correlation coefficient (ICC) analysis showed almost perfect reproducibility (>0.90) for ADC_mean, ADC_min, SUV_max and SUV_mean values for intra-observer and inter-observer agreement. Mean ADC_mean and ADC_min in HNSCC were 1.05?±?0.34 × 10^?3?mm²/s and 0.65?±?0.29 × 10^?3?mm²/s, respectively. Mean SUV_mean and mean SUV_max were 7.61?±?3.87 and 12.8?±?5.0, respectively. Although statistically not significant, a trend towards higher SUV and lower ADC was observed with increasing tumour dedifferentiation. Pearson’s correlation analysis showed no significant correlation between ADC and SUV measurements (r ?0.103, ?0.051; p 0.552, 0.777).

Conclusion

Our data suggest that ADC and SUV values are reproducible and independent biomarkers in HNSCC.     

Functional imaging of lung cancer using dual energy CT: how does iodine related attenuation correlate with standardized uptake value of 18FDG-PET-CT?

Objectives

To investigate the correlation between maximum standardized uptake value (SUV_max) of ¹⁸FDG PET-CT and iodine-related attenuation (IRA) of dual energy CT (DECT) of primary tumours and ¹⁸FDG PET-CT positive thoracic lymph nodes (LN) in patients with lung cancer.

Methods

37 patients with lung cancer (27 NSCLC, 10 SCLC, 86 ¹⁸FDG PET-CT positive thoracic LN) who underwent both ¹⁸FDG PET-CT and DECT were analyzed. The mean study interval between ¹⁸FDG PET-CT and DECT was ??21?days in 17 patients. The mean and maximum IRA of DECT as well as of virtual unenhanced and virtual 120?kV images of DECT was analyzed and correlated to the SUV_max of ¹⁸FDG PET-CT in all tumours and ¹⁸FDG PET-CT positive thoracic lymph nodes. Further subgroup analysis was performed for histological subtypes in all groups.

Results

A moderate correlation was found between SUV_max and maximum IRA in all tumours (n?=?37;r?=?0.507;p?=?0.025) whereas only weak or no correlation were found between SUV_max and all other DECT measurements. A strong correlation was found in patients with study intervals ??21?days (n?=?17; r?=?0.768;p?=?0.017). Analysis of histological subtypes of lung cancer showed a strong correlation between SUV_max and maximum IRA in the analysis of all patients with NSCLC (r?=?0.785;p?=?0.001) and in patients with NSCLC and study intervals ??21?days (r?=?0.876;p?=?0.024). Thoracic LN showed moderate correlation between SUV_max and maximum IRA in patients with study intervals ??21?days (r?=?0.654; p?=?0.010) whereas a weak correlation was found between SUV_max and maximum IRA in patients with study intervals >21?days (r?=?0.299; p?=?0.035).

Conclusions

DECT could serve as a valuable functional imaging test for patients with NSCLC as the IRA of DECT correlates with SUV_max of ¹⁸FDG PET-CT.     

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.