Standardized added metabolic activity (SAM): a partial volume independent marker of total lesion glycolysis in liver metastases

Purpose

The standardized added metabolic activity (SAM) is a new marker of total lesion glycolysis that avoids partial volume effect (PVE) and thresholding. SAM is calculated by drawing a volume of interest (VOI₁) around the tumour and a larger VOI (VOI₂) around VOI₁. Subtracting the background activity in VOI₂-VOI₁ from VOI₁ yields SAM. If VOI₁ is set at a reasonable distance from the tumour, PVE are avoided. Phantom and initial clinical validation data are presented.

Methods

Spheres of a Jaszczak phantom were filled with a 5.4, 3.64 and 2.0 times higher concentration relative to background activity and positron emission tomography (PET) data were acquired during 10?min. SAM of all spheres was expressed as a percentage of the expected value (the actual activity ratio minus 1). In 15 patients a 10-min list-mode acquisition PET study centred on their primary squamous cell carcinoma (PSCC) was performed and images of 1-10?min reconstructed. SAM1-9min values of PSCC were expressed as a percentage of SAM10min. Nineteen patients suffering from liver metastases treated with chemotherapy underwent PET/CT prior to (scan 1) and after 3–6 cycles of chemotherapy (scan 2). SAM and maximum standardized uptake values (SUV_max) of the liver lesions on scan 1 (SAM1 and SUV_max1) and the percentage reduction between both ΔSAM and ΔSUV_max were related to Response Evaluation Criteria in Solid Tumors (RECIST) response.

Results

For the phantom acquisitions, the mean normalized SAM/sphere volume calculated was 94.9?% (SD 5.9?%) of the expected value. In the PSCC patients, the mean difference between SAM1min and SAM10min was only 4?% (SD 5?%). SUV_max1min and SUV_max10min proved to be not significantly different, but the variability was slightly larger than that of SAM (SD 6.4?%). SAM1 and ΔSAM values for responders versus non-responders were, respectively, 57 (SD 119) versus 297 (SD 625) for SAM1 (p?=?0.2) and 99?% (SD 3?%) versus 32?% (SD 44?%) for ΔSAM (p?=?0.001). SUV_max1 and ΔSUV_max values in responders versus non-responders were, respectively, 3.9 (SD 2.4) versus 6.3 (SD 3.1) for SUV_max1 (p?=?0.08) and 94?% (SD 17) versus 7?% (SD 40?%) for ΔSUV_max (p?=?0.0001). The AUC of ΔSAM and ΔSUV_max were not significantly different on receiver-operating characteristic (ROC) analysis (AUC 1.0 and 0.99, respectively, p?=?0.6).

Conclusion

SAM is a promising parameter for tumour response assessment of liver metastases by means of ¹⁸F-fluorodeoxyglucose PET.     

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.     

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.     

Interim FDG PET/CT as a prognostic factor in diffuse large B-cell lymphoma

Purpose

Interim ¹⁸F-FDG PET performed early during the course of therapy in diffuse large B-cell lymphoma (DLBCL) is a good predictor of outcome. However, interpretation criteria for interim PET for the evaluation of tumour response are still not clearly defined. The study aim was to assess whether interim PET can predict overall survival (OS) and progression-free survival (PFS) in DLBCL patients following three different sets of parameters, two qualitative (visual) methods and one semiquantitative.

Methods

A total of 50 newly diagnosed DLBCL patients were prospectively enrolled in this study. All patients had a PET/CT scan at diagnosis and an interim PET/CT scan after the second or third cycle of chemotherapy. Three methods of evaluation for the interim PET/CT were used: a qualitative three-point scoring (3-PS) method, a qualitative 5-PS method and a semiquantitative method (ΔSUV_max). The degree of correlation between therapy response seen on FDG PET and PFS and OS was determined.

Results

The analysis of the visual 3-PS method showed no statistically significant difference in PFS and OS. The estimated 5-year PFS and OS were 79 % and 92 %, respectively, in patients with an interim PET scan showing uptake not greater than in the liver versus 50 % in patients with uptake greater than in the liver, and this difference was statistically significant. The optimal cut-off value of ΔSUV_max that could predict the PFS and OS difference in patients with DLBCL was 76 % (95 % CI 62.7–89.2 %) and 75 % (95 % CI, 54.6–95.4 %), respectively.

Conclusion

Our results support the use of liver uptake as an indicator in the qualitative evaluation of interim PET, or a ΔSUV_max greater than 75 % in semiquantitative analysis. Interim PET may predict PFS and OS and could be considered in the prognostic evaluation of DLBCL.     

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

Purpose

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

Methods

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

Results

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

Conclusion

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

Total lesion glycolysis (TLG) as an imaging biomarker in metastatic colorectal cancer patients treated with regorafenib

Purpose

This study was performed to evaluate whether fluorine-18 fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) could predict treatment outcome of regorafenib in metastatic colorectal cancer (mCRC).

Methods

Previously treated refractory mCRC patients were enrolled into a prospective biomarker study of regorafenib. For this sub-study, the results of FDG PET/CT scans at baseline and after two cycles of treatment were analyzed. Various metabolic parameters obtained from PET images were analyzed in relation to treatment outcome.

Results

A total of 40 patients were evaluable for PET image analysis. Among various PET parameters, total lesion glycolysis (TLG) measured in the same target lesions for RECIST 1.1 analysis were the most significant in predicting prognosis, with the lowest p-value observed in TLG calculated using the margin threshold of 40 % (TLG_{40 %}). Further analysis using TLG_{40 %} showed significantly longer overall survival (OS) in patients with lower baseline TLG_{40 %} (<151.8) (p?=?0.003, median 14.2 vs. 9.1 months in <151.8 and ≥151.8, respectively). Patients showing higher decrease in TLG_{40 %} after treatment showed significantly longer progression-free survival (PFS) (p?=?0.001, median 8.0 vs. 2.4 months in %ΔTLG_{40 %}?<??9.6 % and?≥??9.6 %, respectively) and OS (p?=?0.002, median 16.4 vs. 9.1 months in %ΔTLG_{40 %}?<??9.6 % and?≥??9.6 %, respectively). The same cutoff could discriminate patients with longer survival among the patients who were under the stable disease category according to RECIST 1.1 (median PFS 8.4 vs. 6.8 months, p?=?0.020; median OS 18.3 vs. 11.5 months, p?=?0.049).

Conclusion

Measurement of TLG can predict treatment outcome of regorafenib in mCRC.

     

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.     

The role of early 18F-FDG PET/CT in prediction of progression-free survival after 90Y radioembolization: comparison with RECIST and tumour density criteria

Purpose

This study evaluated the ability of ¹⁸F-FDG PET/CT imaging to predict early response to ⁹⁰Y-radioembolization in comparison with contrast-enhanced CT (CECT) using RECIST and lesion density (Choi) criteria. Progression-free survival (PFS) in patients with liver metastases at 2?years and decline in tumour markers were the primary end-points of the study.

Methods

A total of 121 liver lesions were evaluated in 25 patients (14 men, 11 women) with liver-dominant metastatic colorectal cancer who underwent ¹⁸F-FDG PET/CT and CECT before and 6–8?weeks after treatment. Changes in SUV_max, tumour density measured in terms of Hounsfield units and the sum of the longest diameters (LD) were calculated for the target liver lesions in each patient. The patient responses to treatment were categorized using EORTC PET criteria, tumour density criteria (Hounsfield units) and RECIST, and were correlated with the responses of tumour markers and 2-year PFS using Kaplan-Meier plots and the log-rank test for comparison. Multivariate proportional hazards (Cox) regression analysis was performed to assess the effect of relevant prognostic factors on PFS.

Results

Using ¹⁸F-FDG PET/CT response criteria, 15 patients had a partial response (PR) and 10 patients had stable disease (SD), while using RECIST only 2 patients had a PR and 23 had SD. Two patients had a PR, 21 SD and 2 progressive disease using tumour density criteria. The mean changes in SUV_max, sum of the LDs and tumour density after treatment were 2.9?±?2.6, 7.3?±?14.4?mm and 1.9?±?13.18?HU, respectively. Patients who had a PR on ¹⁸F-FDG PET/CT had a mean decrease of 44.5?% in SUV_max compared to those with SD who had a decrease of only 10.3?%. The decreases in SUV_max and sum of the LDs were significant (p?p?p?>?0.1065). The responses on the ¹⁸F-FDG PET/CT studies were highly correlated with the responses of tumour markers (p?p?=?0.01 for CEA and p?=?0.02 for Ca19-9), while the responses on the CECT studies using both RECIST and tumour density criteria were not significantly correlated with the responses of tumour markers. The responses on ¹⁸F-FDG PET/CT studies also significantly predicted PFS (the median PFS in those with a PR was 12.0?months and in those with SD was 5?months, p?18F-FDG PET/CT studies and decreases in SUV_max of ≤2.0 were the strongest predictors of PFS.

Conclusion

Early response assessment to ⁹⁰Y-radioembolization using ¹⁸F-FDG PET/CT is superior to RECIST and tumour density, demonstrating a correlation with tumour markers and significantly predicting PFS in patients with liver metastases. This could enable early response-adapted treatment strategies to be employed.     

Diagnostic accuracy of 68Ga-DOTANOC PET/CT imaging in pheochromocytoma

Purpose

The purpose of the present study was to evaluate the diagnostic accuracy of ⁶⁸Ga-DOTANOC positron emission tomography (PET)/CT in patients with suspicion of pheochromocytoma.

Methods

Data of 62 patients [age 34.3?±?16.1 years, 14 with multiple endocrine neoplasia type 2 (MEN2)] with clinical/biochemical suspicion of pheochromocytoma and suspicious adrenal lesion on contrast CT (n?=?70), who had undergone ⁶⁸Ga-DOTANOC PET/CT, were retrospectively analyzed. PET/CT images were analyzed visually as well as semiquantitatively, with measurement of maximum standardized uptake value (SUV_max), SUV_mean, SUV_max/SUV_liver, and SUV_mean/SUV_liver. Results of PET/CT were compared with ¹³¹I-metaiodobenzylguanidine (MIBG) imaging, which was available in 40 patients (45 lesions). Histopathology and/or imaging/clinical/biochemical follow-up (minimum 6 months) was used as reference standard.

Results

The sensitivity, specificity, and accuracy of ⁶⁸Ga-DOTANOC PET/CT was 90.4, 85, and 88.7 %, respectively, on patient-based analysis and 92, 85, and 90 %, respectively, on lesion-based analysis. ⁶⁸Ga-DOTANOC PET/CT showed 100 % accuracy in patients with MEN2 syndrome and malignant pheochromocytoma. On direct comparison, lesion-based accuracy of ⁶⁸Ga-DOTANOC PET/CT for pheochromocytoma was significantly higher than ¹³¹I-MIBG imaging (91.1 vs 66.6 %, p?=?0.035). SUV_max was higher for pheochromocytomas than other adrenal lesions (p?=?0.005), MEN2-associated vs sporadic pheochromocytoma (p?=?0.012), but no difference was seen between benign vs malignant pheochromocytoma (p?=?0.269).

Conclusion

⁶⁸Ga-DOTANOC PET/CT shows high diagnostic accuracy in patients with suspicion of pheochromocytoma and is superior to ¹³¹I-MIBG imaging for this purpose. Best results of ⁶⁸Ga-DOTANOC PET/CT are seen in patients with MEN2-associated and malignant pheochromocytoma.     

SUV<Subscript>max</Subscript> on FDG-PET is a predictor of prognosis in patients with maxillary sinus cancer

Purpose

Our aim was to determine whether the maximum standardized uptake value (SUV_max) of the primary lesion demonstrated by [¹⁸F]-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is associated with the prognosis of maxillary sinus cancer.

Materials and methods

The relationships of clinicopathological factors including age, T stage, N stage, histologic type, treatment strategy, and primary tumor SUV_max with progression-free (PFS) and overall (OS) survival were evaluated using the log-rank test and Cox method in 31 patients with maxillary sinus cancer before combined superselective intra-arterial chemotherapy using high-dose cisplatin with concurrent radiotherapy, or radiotherapy alone.

Results

The median duration of follow-up was 55.4 (range 9.7–72.6) months. PFS and OS of patients exhibiting a high SUV_max (≥16 and ≥17, respectively) for the primary tumor were significantly lower than those of patients for whom the primary tumor SUV_max was low (p = 0.0010 and p = 0.033, respectively). Multivariate analyses showed that T stage (p = 0.0049) and primary tumor SUV_max (p = 0.026) were independently prognostic of poorer PFS and that only primary tumor SUV_max (p = 0.049) was independently prognostic of poorer OS.

Conclusion

SUV_max of the primary tumor determined by FDG-PET/CT before treatment could be a good surrogate marker for prognostication of maxillary sinus cancer.

     

Prognostic value of pre-treatment <Superscript>18</Superscript>F-FDG-PET uptake in small-cell lung cancer

Purpose

Small-cell lung cancer (SCLC) is an aggressive disease, despite an initially favorable response to treatment, and its prognosis is still poor. Multiple parameters have been studied as possible prognostic factors, but none of them are reliable enough to change the treatment approach. ¹⁸F-fluorodeoxyglucose-positron emission tomography (FDG-PET) is a novel imaging technique for staging of SCLC. The aim of this study was to evaluate the prognostic value of pre-treatment FDG-PET parameters on clinical outcome in limited stage (LS) SCLC patients treated with curative thoracic radiotherapy (RT) and chemotherapy.

Methods

Clinical records of 46 LS-SCLC patients with pre-treatment FDG-PET imaging were retrospectively reviewed. Patients were treated with definitive RT for a total dose of 50–60 Gy and chemotherapy. The clinical endpoints were progression-free survival (PFS) and overall survival (OS).

Results

The median age was 59 (range 30–82) years, and median follow-up time was 23.2 months (range 5–82.8 months). Median OS was 30.9 months for pre-treatment tumor maximum standardized uptake value (SUV_max) <9.3 and 20.6 months for SUV_max ≥9.3 (p = 0.027) and PFS was 55.6 months for SUV_max <9.3 and 38.6 months for SUV_max ≥9.3 (p = 0.16). Median OS was 73 months for pre-treatment lymph node SUV_max <5.8 and 21 months for ≥5.8 (p = 0.01) and PFS was 38.6 months (range 6.8–70.3 months) for SUV_max-LN ≥5.8; all patients with SUV_max-LN <5.8 were alive (p = 0.07). Median survival time was 28.2 months (range 21.7–34.7 months) for patients younger than 65 and 8.7 months (range 5.7–11.8 months) for those ≥65 years (p = 0.00).

Conclusions

Pre-treatment FDG-PET uptake may be a valuable tool to evaluate prognosis in SCLC patients. Patients with a higher pre-treatment FDG uptake may be considered at increased risk of failure and may benefit from more aggressive treatment approaches.

     

Preoperative PET/CT FDG standardized uptake value of pelvic lymph nodes as a significant prognostic factor in patients with uterine cervical cancer

Purpose

Using integrated PET/CT, we evaluated the prognostic relevance in uterine cervical cancer of preoperative pelvic lymph node (LN) [¹⁸F]FDG uptake.

Methods

Patients with FIGO stage IB to IIA uterine cervical cancer were imaged with FDG PET/CT before radical surgery. We used Cox proportional hazards regression to examine the relationship between recurrence and the FDG maximum standardized uptake value (SUV_max) in the pelvic LN (SUV_LN) on PET/CT.

Results

Clinical data, treatment modalities, and results in 130 eligible patients were reviewed. The median postsurgical follow-up was 34 months (range 6 to 109 months). Receiver operating characteristic analysis identified SUV_LN 2.36 as the most significant cut-off value for predicting recurrence. SUV_LN was correlated with SUV_tumour (P?=?0.002), primary tumour size (P?=?0.004), and parametrial invasion (P?=?0.013). Univariate analyses showed significant associations between recurrence and SUV_LN (P?=?0.001), SUV_tumour (P?=?0.007), pelvic LN metastasis (P?=?0.002), parametrial invasion (P?<?0.001), primary tumour size (P?=?0.007), suspected LN metastasis on MRI (P?=?0.024), and FIGO stage (P?=?0.026). Multivariate analysis identified SUV_LN (P?=?0.013, hazard ratio, HR, 4.447, 95 % confidence interval, CI, 1.379 – 14.343) and parametrial invasion (P?=?0.013, HR 6.728, 95 % CI 1.497 – 30.235) as independent risk factors for recurrence. Patients with SUV_LN ≥2.36 and SUV_LN <2.36 differed significantly in terms of recurrence (HR 15.20, P?<?0.001).

Conclusion

Preoperative pelvic LN FDG uptake showed a strong significant association with uterine cervical cancer recurrence.     

The prognostic value of mid- and post-treatment [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in indolent follicular lymphoma

Background

[¹⁸F]fluorodeoxyglucose positron emission tomography (PET) is a useful staging investigation for follicular lymphoma (FL). Recent studies have shown that positive post-treatment PET is also a strong predictor of inferior overall survival.

Purpose

To evaluate the predictive value of mid- and post-treatment PET in FL patients with respect to progression-free survival (PFS) and overall survival (OS).

Methods

We included 57 patients with indolent FL (grade 1, 2, and 3a) who received induction chemotherapy. Mid- and post-treatment PET results were correlated with PFS and OS retrospectively and analysed using Kaplan–Meier survival analysis and Cox regression.

Results

Post-treatment PET was predictive of OS (mean OS 95.2 vs. 45.0 months for PET-negative vs. PET-positive, p < 0.001) and showed a trend towards significance for PFS (mean PFS 74.4 vs. 38.2 months for PET? vs. PET+, p = 0.083). 3-year PFS for post-treatment PET? and PET+ patients were 72 and 30 %, respectively. 3-year OS were 96 and 60 %, respectively. Mid-treatment PET was not predictive of PFS (mean PFS 78.5 vs. 51.0 months for PET? vs. PET+, p = 0.35) nor OS (mean OS 89.9 vs. 76.6 months for PET? vs. PET+, p = 0.92).

Conclusion

Post-treatment PET is predictive of OS in indolent FL. It identifies patients who might benefit from more intensive follow-up, enrolment in clinical trials or second-line therapy. Mid-treatment PET scan results did not appear to predict long-term treatment outcomes.     

Superior prognostic utility of gross and metabolic tumor volume compared to standardized uptake value using PET/CT in head and neck squamous cell carcinoma patients treated with intensity-modulated radiotherapy

Objective

To compare the prognostic utility of the 2-[¹⁸F] fluoro-2-deoxy-d-glucose (FDG) maximum standardized uptake value (SUV_max), primary gross tumor volume (GTV), and FDG metabolic tumor volume (MTV) for disease control and survival in patients with head and neck squamous cell carcinoma (HNSCC) undergoing intensity-modulated radiotherapy (IMRT).

Methods

Between 2007 and 2011, 41 HNSCC patients who underwent a staging positron emission tomography with computed tomography and definitive IMRT were identified. Local (LC), nodal (NC), distant (DC), and overall (OC) control, overall survival (OS), and disease-free survival (DFS) were assessed using the Kaplan?CMeier product-limit method.

Results

With a median follow-up of 24.2?months (range 2.7?C56.3?months) local, nodal, and distant recurrences were recorded in 10, 5, and 7 patients, respectively. The median SUV_max, GTV, and MTV were 15.8, 22.2?cc, and 7.2?cc, respectively. SUV_max did not correlate with LC (p?=?0.229) and OS (p?=?0.661) when analyzed by median threshold. Patients with smaller GTVs (<22.2?cc) demonstrated improved 2-year actuarial LC rates of 100 versus 56.4?% (p?=?0.001) and OS rates of 94.4 versus 65.9?% (p?=?0.045). Similarly, a smaller MTV (<7.2?cc) correlated with improved 2-year actuarial LC rates of 100 versus 54.2?% (p?p?=?0.04). Smaller GTV and MTV correlated with improved NC, DC, OC, and DFS, as well.

Conclusion

GTV and MTV demonstrate superior prognostic utility as compared to SUV_max, with larger tumor volumes correlating with inferior local control and overall survival in HNSCC patients treated with definitive IMRT.     

18F-FDG PET predicts survival after pretargeted radioimmunotherapy in patients with progressive metastatic medullary thyroid carcinoma

Purpose

PET is a powerful tool for assessing targeted therapy. Since ¹⁸F-FDG shows a potential prognostic value in medullary thyroid carcinoma (MTC), this study evaluated ¹⁸F-FDG PET alone and combined with morphological and biomarker evaluations as a surrogate marker of overall survival (OS) in patients with progressive metastatic MTC treated with pretargeted anti-CEA radioimmunotherapy (pRAIT) in a phase II clinical trial.

Methods

Patients underwent PET associated with morphological imaging (CT and MRI) and biomarker evaluations, before and 3 and 6 months, and then every 6 months, after pRAIT for 36 months. A combined evaluation was performed using anatomic, metabolic and biomarker methods. The prognostic value of the PET response was compared with demographic parameters at inclusion including age, sex, RET mutation, time from initial diagnosis, calcitonin and CEA concentrations and doubling times (DT), SUV_max, location of disease and bone marrow involvement, and with response using RECIST, biomarker concentration variation, impact on DT, and combined methods.

Results

Enrolled in the study were 25 men and 17 women with disease progression. The median OS from pRAIT was 3.7 years (0.2 to 6.5 years) and from MTC diagnosis 10.9 years (1.7 to 31.5 years). After pRAIT, PET/CT showed 1 patient with a complete response, 4 with a partial response and 24 with disease stabilization. The combined evaluation showed 20 responses. For OS from pRAIT, univariate analysis showed the prognostic value of biomarker DT (P?=?0.011) and SUV_max (P?=?0.038) calculated before pRAIT and impact on DT (P?=?0.034), RECIST (P?=?0.009), PET (P?=?0.009), and combined response (P?=?0.004) measured after pRAIT. PET had the highest predictive value with the lowest Akaike information criterion (AIC 74.26) as compared to RECIST (AIC 78.06), biomarker variation (AIC 81.94) and impact on DT (AIC 79.22). No benefit was obtained by combining the methods (AIC 78.75). This result was confirmed by the analysis of OS from MTC diagnosis.

Conclusion

¹⁸F-FDG PET appeared as the most potent and simplest prognostic method to predict survival in patients with progressive MTC treated with pRAIT. Biomarker DT before pRAIT also appeared as an independent prognostic factor, but no benefit was found by adding morphological and biomarker evaluation to PET assessment.     

Impact of initial PET/CT staging in terms of clinical stage,management plan,and prognosis in 592 patients with non-small-cell lung cancer

Purpose

Our objective was to determine the impact of initial ¹⁸F-FDG PET/CT (PET/CT) staging on clinical stage and the management plan and the prognostic value of PET/CT in patients with non-small-cell lung cancer (NSCLC).

Methods

We retrospectively reviewed the records of 592 patients with NSCLC who were referred to The University of Texas MD Anderson Cancer Center during 2002/2011 and had both PET/CT and conventional CT for initial staging. Clinical stages and management plans were compared between PET/CT and CT. The impact of PET/CT on management plans was considered medium/high when PET/CT changed the planned treatment modality or treatment intent. PET/CT and CT stages were compared with all-cause mortality and survival rates. We also assessed potential prognostic factors for progression-free survival (PFS) and overall survival (OS).

Results

PET/CT changed the stage in 170 patients (28.7 %; 16.4 % upstaged, 12.3 % downstaged). PET/CT had a medium/high impact on the management plan in 220 patients (37.2 %). PFS and OS were significantly worse in patients with upstaged disease than in patients with no change in stage (median PFS 29.0 vs. 53.8 months, P?<?0.001; median OS:64.7 vs. 115.9 months, P?=?0.006). PFS and OS were significantly worse in patients with medium/high impact of PET/CT than in patients with no/low impact of PET/CT (median PFS 24.7 vs. 60.6 months, P?<?0.001; median OS 64.7 vs. 115.9 months, P?<?0.001). In multivariate analysis, a medium/high impact of PET/CT was an independent predictor of worse PFS (hazard ratio, HR, 1.73; 95 % CI 1.30 – 2.29; P?=?0.0002) and OS (HR 1.84; 95 % CI 1.26 – 2.69; P?=?0.002).

Conclusion

Initial PET/CT staging not only impacts stage and management plan but also has prognostic value.     

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.     

Preoperative PET/CT standardized FDG uptake values of pelvic lymph nodes as a significant prognostic factor in patients with endometrial cancer

Purpose

Using integrated PET/CT, we evaluated the prognostic relevance of preoperative pelvic lymph node (LN) ¹⁸F-FDG uptake in endometrioid endometrial cancer.

Methods

We retrospectively reviewed patients with pathologically proven endometrial cancer who underwent preoperative ¹⁸F-FDG PET/CT scans to evaluate the prognostic significance of PET/CT parameters and other clinicopathological variables. We used Cox proportional hazards regression to examine the relationship between recurrence and the maximum standardized uptake value (SUV_max) in pelvic LNs (SUV_LN) on FDG PET/CT.

Results

Clinical data, treatment modalities and results were reviewed in 70 eligible patients. The median postsurgical follow-up was 29 months (range 6 to 95 months). Receiver-operating characteristic analysis identified the significant SUV_LN cut-off value as 15. The SUV_LN correlated with FIGO stage (P?<?0.001), LN metastasis (P?<?0.001), lymphovascular space invasion (P?<?0.001), SUV_tumour (P?=?0.001), metastatic LN size (P?=?0.004), primary tumour size (P?=?0.012), tumour grade (P?=?0.015) and depth of tumour invasion (P?=?0.035). Regression analysis showed a statistically significant association between recurrence and SUV_LN (P?=?0.002). Recurrence differed significantly (P?<?0.001) between patients with SUV_LN >15 and those with SUV_LN ≤15.

Conclusion

Preoperative pelvic LN FDG uptake exhibited a strong significant association with recurrence of endometrioid endometrial cancer.     

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.     

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.