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.     

An international confirmatory study of the prognostic value of early PET/CT in diffuse large B-cell lymphoma: comparison between Deauville criteria and ΔSUVmax

Purpose

The role of interim PET/CT in guiding therapeutic strategies in diffuse large B-cell lymphoma (DLBCL) is debated, mainly because interpretation rules vary among centres. This study aimed to explore the reproducibility and confirm the prognostic value of early PET/CT using the Deauville criteria and ΔSUVmax.

Methods

This international confirmatory study retrospectively evaluated 114 patients with newly diagnosed DLBCL treated with a rituximab-containing regimen. All patients underwent ¹⁸F-FDG PET/CT at baseline (PET0) and after two cycles (PET2), with no therapy change based on the latter. Scans were interpreted by three observers using the Deauville five-point scale and ΔSUVmax between PET0 and PET2 was calculated. Interpretations were evaluated for interobserver agreement and for progression-free survival (PFS) prediction.

Results

Median follow-up was 39 months. Early PET/CT was predictive of outcome when interpreted with the Deauville criteria and ΔSUVmax. Using the five-point scale, the overall kappa value was 0.66 with the reference background set in the liver (score ≥4) and interobserver agreement was even better using a 66 % ΔSUVmax cut-off (κ?=?0.83). Moreover, the prognostic value of interim PET was slightly inferior when using a Deauville score ≥4 than when using a 66 % ΔSUVmax cut-off: for the Deauville score the 3-year PFS estimate was 59 % (45–73 %) in PET2-positive patients vs. 81 % (71–91 %) in PET2-negative patients (P?=?0.003); for the 66 % ΔSUVmax cut-off the 3-year PFS estimate was 44 % (23–65 %) in PET2-positive patients vs. 79 % (70–88 %) in PET2-negative patients (P?=?0.0002).

Conclusion

Although the Deauville criteria are valid for assessing the prognostic value of early PET/CT in DLBCL, computation of the ΔSUVmax leads to better performance and interobserver reproducibility, and should be preferred when a baseline scan is available.     

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.     

18F-FDG-PET/CT predicts survival in hypopharyngeal squamous cell carcinoma

Objectives

We investigated the relationship between overall survival of patients and pretreatment [¹⁸F]-2-fluorodeoxyglucose (¹⁸F-FDG) uptake, assessed by positron emission tomography combined with computed tomography (PET/CT) in hypopharyngeal squamous cell carcinoma.

Methods

Thirty-one patients who were newly diagnosed as resectable hypopharyngeal squamous cell carcinoma underwent pretreatment ¹⁸F-FDG-PET/CT. We used the maximum standardized uptake value (SUVmax) as ¹⁸F-FDG uptake. Overall survival rate was calculated by the Kaplan–Meier method.

Results

The median SUVmax was 11.53 (range 2.49–22.33). Patients with SUVmax ≥ 13 significantly exhibited shorter overall survival in univariate analysis (p < 0.01). Moreover, by Cox proportional hazards model of multivariate analysis, SUVmax ≥ 13 was a significant prognostic factor independent of clinical T and N classification, and treatment group (p < 0.02).

Conclusions

These results suggested that SUVmax obtained by pretreatment ¹⁸F-FDG PET/CT assessment is an important prognostic factor in patients with hypopharyngeal squamous cell carcinoma.     

Prognostic value of whole-body metabolic tumour volume and total lesion glycolysis measured on 18F-FDG PET/CT in patients with extranodal NK/T-cell lymphoma

Purpose

The aim of this study was to determine whether maximum standardized uptake value (SUVmax), whole-body metabolic tumour volume (WBMTV), and whole-body total lesion glycolysis (WBTLG) measured on pretreatment ¹⁸F-FDG PET/CT can predict prognosis in patients with extranodal natural killer/T-cell lymphoma (ENKTL).

Methods

We conducted a retrospective analysis of 20 patients with newly-diagnosed ENKTL who underwent pretreatment ¹⁸F-FDG PET/CT. WBMTV and WBTLG were measured automatically using the boundaries of voxels presenting SUV?>?3.0. Uni- and multivariate analyses for survival and disease progression were performed using clinical variables and PET parameters (SUVmax, WBMTV, and WBTLG).

Results

During the follow-up period (median 26.3 months), 12 patients showed disease progression and 10 patients died from the disease. Receiver operating characteristic curve analysis showed cut-off values for SUVmax, WBMTV and WBTLG of 8.1, 14.4 cm³ and 52.7, respectively. Univariate analysis showed that the International Prognostic Index (IPI) score and PET parameters were significant predictors of overall survival (OS) and progression-free survival (PFS). Multivariate analysis, even after adjustment for the IPI score, showed that high WBMTV was the best predictor of OS and PFS, and high SUVmax and WBTLG were significant predictors of PFS.

Conclusion

Our results suggested that the use of PET parameters together with the IPI score may be useful for detailed prediction of prognosis in ENKTL patients. Therefore, despite a lower IPI score, patients with high PET parameter values might be considered candidates for aggressive therapy to improve clinical outcomes.     

Prognostic value of 18F-fluorodeoxyglucose uptake before treatment for pharyngeal cancer

Objectives

The purpose of this study was to evaluate an association found between overall survival of patients with pharyngeal squamous cell carcinoma (SCC) and pretreatment [¹⁸F]-2-fluorodeoxyglucose (¹⁸F-FDG) uptake, which are assessed by positron emission tomography combined with computed tomography (PET/CT). Next, we asked whether ¹⁸F-FDG uptake is correlated with overall survival in patients with pharyngeal SCC who underwent radical treatments such as surgery and radiotherapy in the multivariate analysis with adjustments for the clinical stage, primary site and treatment group.

Methods

Forty-nine patients who were newly diagnosed as resectable pharyngeal SCC underwent pretreatment ¹⁸F-FDG-PET/CT. We used the maximum standardized uptake value (SUVmax) as ¹⁸F-FDG uptake. Overall survival rate was calculated by the Kaplan–Meier method. Univariate survival analysis was analyzed by log-rank test, and multivariate survival analysis was performed by a Cox proportional hazards model.

Results

Patients with SUVmax of the primary site ≥8 significantly exhibited shorter overall survival in univariate analysis (p < 0.04). Moreover, SUVmax of the primary site ≥8 was a significant prognostic factor in the multivariate analysis (p < 0.03).

Conclusions

These results suggested that SUVmax of the primary site obtained by pretreatment ¹⁸F-FDG-PET/CT assessment is an important prognostic factor in patients with pharyngeal SCC.     

Diagnostic accuracy of 18F-FDG PET/CT for detecting recurrence in patients with primary skeletal Ewing sarcoma

Purpose

To evaluate the diagnostic accuracy of ¹⁸F-FDG PET/CT for detecting recurrence in patients with primary skeletal Ewing sarcoma.

Methods

We retrospectively analysed data from 53 patients (age 20.1?±?10.5 years, 39 male) who had undergone 71 ¹⁸F-FDG PET/CT studies for suspected recurrence (52 studies) or for routine follow-up (19 studies) after primary therapy of skeletal Ewing sarcoma. ¹⁸F-FDG PET/CT studies were evaluated qualitatively and quantitatively (maximum standardized uptake value, SUVmax) by two nuclear medicine physicians in consensus. Sensitivity, specificity, predictive values and accuracy were calculated on per study basis. Clinical/imaging follow-up (minimum 6 months) and/or histopathology (when available) were taken as the reference standard.

Results

Of the total of 71 ¹⁸F-FDG PET/CT studies, 42 (59.1 %) were positive for recurrence and 29 (40.9 %) were negative for recurrence. Local recurrence was most common (38 studies) followed by bone metastasis (9 studies), and node and lung metastasis (2 studies each). Of the 71 studies, 38 were true-positive, 27 were true-negative, 4 were false-positive and 2 were false-negative. Overall per study based sensitivity was 95 %, specificity was 87 %, PPV was 90 %, NPV was 93 % and accuracy was 91.5 %. No significant difference was found in the accuracy of PET/CT between the suspected recurrence group and the routine follow-up group (94 % vs. 84 %; P?=?0.390). Overall mean lesion SUVmax was 7.8?±?4.1 (range 1.9–17.2). No site-based difference was found in SUVmax.

Conclusion

¹⁸F-FDG PET/CT demonstrates high diagnostic accuracy for detecting recurrence in patients with primary skeletal Ewing sarcoma, when it is suspected (clinically or on imaging) or during routine follow-up.     

Volume-based assessment by 18F-FDG PET/CT predicts survival in patients with stage III non-small-cell lung cancer

Purpose

We evaluated the prognostic impact of volume-based assessment by ¹⁸F-FDG PET/CT in patients with stage III non-small-cell lung cancer (NSCLC).

Methods

We reviewed 194 consecutive patients with stage IIIA NSCLC treated with surgical resection (surgical group) and 115 patients treated with nonsurgical therapy (nonsurgical group: 50 stage IIIA, 65 stage IIIB). Metabolic tumour volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) of primary tumours were measured using pretreatment ¹⁸F-FDG PET/CT. Overall survival was assessed using the Kaplan-Meier method. The prognostic significance of PET parameters and other clinical variables was assessed using Cox proportional hazards regression analyses. To evaluate and compare the predictive performance of PET parameters, time-dependent receiver operating characteristic (ROC) curve analysis was used.

Results

In the Cox proportional hazards models, MTV (HR?=?1.27 for a doubling of MTV, P?=?0.008) and TLG (HR?=?1.22 for a doubling of TLG, P?=?0.035) were significantly associated with an increased risk of death after adjusting for age, gender, histological cell type, T stage, N stage, and treatment variables in the surgical group. SUVmax was not a significant prognostic factor in either the surgical or nonsurgical group. In the time-dependent ROC curve analysis, volume-based PET parameters predicted survival better than SUVmax.

Conclusion

The volume-based PET parameters (MTV and TLG) are significant prognostic factors for survival independent of tumour stage and better prognostic imaging biomarkers than SUVmax in patients with stage IIIA NSCLC after surgical resection.     

18F-FDG PET/CT provides powerful prognostic stratification in the primary staging of large breast cancer when compared with conventional explorations

Purpose

The objective of this study was to assess the impact on management and the prognostic value of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT for initial staging of newly diagnosed large breast cancer (BC) when compared with conventional staging.

Methods

We prospectively included 142 patients with newly diagnosed BC and at least grade T2 tumour. All patients were evaluated with complete conventional imaging (CI) procedures (mammogram and/or breast ultrasound, bone scan, abdominal ultrasound and/or CT, X-rays and/or CT of the chest), followed by FDG PET/CT exploration, prior to treatment. The treatment plan based on CI staging was compared with that based on PET/CT findings. CI and PET/CT findings were confirmed by imaging and clinical follow-up and/or pathology when assessable. Progression-free survival (PFS) was analysed using the Cox proportional hazards regression model.

Results

According to CI staging, 79 patients (56 %) were stage II, 46 (32 %) stage III and 17 (12 %) stage IV (distant metastases). Of the patients, 30 (21 %) were upstaged by PET/CT, including 12 (8 %) from stage II or III to stage IV. On the other hand, 23 patients (16 %) were downstaged by PET/CT, including 4 (3 %) from stage IV to stage II or III. PET/CT had a high or medium impact on management planning for 18 patients (13 %). Median follow-up was 30 months (range 9–59 months); 37 patients (26 %) experienced recurrence or progression of disease during follow-up and 17 patients (12 %) died. The Cox model indicated that CI staging was significantly associated with PFS (p?=?0.01), but PET/CT staging provided stronger prognostic stratification (p?<?0.0001). Moreover, Cox regression multivariate analysis showed that only PET/CT staging remained associated with PFS (p?<?0.0001).

Conclusion

FDG PET/CT provides staging information that more accurately stratifies prognostic risk in newly diagnosed large BC when compared with conventional explorations alone.     

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

Purpose

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

Methods

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

Results

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

Conclusion

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

Metabolic response evaluated by 18F-FDG PET/CT as a potential screening tool in identifying a subgroup of patients with advanced non-small cell lung cancer for immediate maintenance therapy after first-line chemotherapy

Purpose

Among patients with advanced non-small cell lung cancer (NSCLC), identification of a subgroup of patients for immediate maintenance treatment after first-line chemotherapy has great importance in improving survival. The purpose of this study was to investigate whether the metabolic responses evaluated by ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) may be a potential screening tool for identifying patients with early disease progression who may benefit from immediate maintenance treatment.

Methods

A total of 52 patients with advanced NSCLC (36 men and 16 women, mean age 57.2?±?10.6 years) who underwent baseline and follow-up ¹⁸F-FDG PET/CT after four cycles of first-line chemotherapy were enrolled. Maximum standardized uptake value (SUV_max), SUV_peak, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of the tumour lesions were measured and percentage decrease of the parameters was calculated. The prognostic significance of percentage decrease of these parameters and other clinical variables related to progression-free survival (PFS) and overall survival (OS) were assessed by Cox proportional hazards regression analysis. Receiver-operating characteristic (ROC) curve analysis was used to define the optimal cut-off value of percentage decrease of the parameters that could distinguish between early (PFS?<?6 months) and late (PFS?≥?6 months) disease progression groups.

Results

Multivariate analysis showed that percentage decrease of TLG [hazard ratio per 10 % decrease?=?1.030, 95 % confidence interval (CI)?=?1.012–1.048, p?=?0.001) was a significant predictor of PFS and OS. ROC curves identified a 50.0 % decrease in TLG as the optimal cut-off value to distinguish disease progression groups. Positive and negative predictive values of the optimal TLG value for selecting patients with late disease progression were 36.4 and 100.0 %, respectively.

Conclusion

The percentage decrease in TLG of measurable tumour lesions may be a potential parameter to appropriately identify a subgroup of patients for immediate maintenance treatment after first-line chemotherapy in patients with advanced NSCLC.     

Metabolic tumour volumes measured at staging in lymphoma: methodological evaluation on phantom experiments and patients

Purpose

The presence of a bulky tumour at staging on CT is an independent prognostic factor in malignant lymphomas. However, its prognostic value is limited in diffuse disease. Total metabolic tumour volume (TMTV) determined on ¹⁸F-FDG PET/CT could give a better evaluation of the total tumour burden and may help patient stratification. Different methods of TMTV measurement established in phantoms simulating lymphoma tumours were investigated and validated in 40 patients with Hodgkin lymphoma and diffuse large B-cell lymphoma.

Methods

Data were processed by two nuclear medicine physicians in Reggio Emilia and Créteil. Nineteen phantoms filled with ¹⁸F-saline were scanned; these comprised spherical or irregular volumes from 0.5 to 650 cm³ with tumour-to-background ratios from 1.65 to 40. Volumes were measured with different SUVmax thresholds. In patients, TMTV was measured on PET at staging by two methods: volumes of individual lesions were measured using a fixed 41 % SUVmax threshold (TMTV₄₁) and a variable visually adjusted SUVmax threshold (TMTV_var).

Results

In phantoms, the 41 % threshold gave the best concordance between measured and actual volumes. Interobserver agreement was almost perfect. In patients, the agreement between the reviewers for TMTV₄₁ measurement was substantial (ρ _c?=?0.986, CI 0.97 – 0.99) and the difference between the means was not significant (212?±?218 cm³ for Créteil vs. 206?±?219 cm³ for Reggio Emilia, P?=?0.65). By contrast the agreement was poor for TMTV_var. There was a significant direct correlation between TMTV₄₁ and normalized LDH (r?=?0.652, CI 0.42 – 0.8, P <0.001). Higher disease stages and bulky tumour were associated with higher TMTV₄₁, but high TMTV₄₁ could be found in patients with stage 1/2 or nonbulky tumour.

Conclusion

Measurement of baseline TMTV in lymphoma using a fixed 41% SUVmax threshold is reproducible and correlates with the other parameters for tumour mass evaluation. It should be evaluated in prospective studies.     

Combined use of 18F-FDG PET/CT and MRI for response monitoring of breast cancer during neoadjuvant chemotherapy

Purpose

To explore the potential complementary value of PET/CT and dynamic contrast-enhanced MRI in predicting pathological response to neoadjuvant chemotherapy (NAC) of breast cancer and the dependency on breast cancer subtype.

Methods

We performed ¹⁸F-FDG PET/CT and MRI examinations before and during NAC. The imaging features evaluated on both examinations included baseline and changes in ¹⁸F-FDG maximum standardized uptake value (SUVmax) on PET/CT, and tumour morphology and contrast uptake kinetics on MRI. The outcome measure was a (near) pathological complete response ((near-)pCR) after surgery. Receiver operating characteristic curves with area under the curve (AUC) were used to evaluate the relationships between patient, tumour and imaging characteristics and tumour responses.

Results

Of 93 patients, 43 achieved a (near-)pCR. The responses varied among the different breast cancer subtypes. On univariate analysis the following variables were significantly associated with (near-)pCR: age (p?=?0.033), breast cancer subtype (p?<?0.001), relative change in SUVmax on PET/CT (p?<?0.001) and relative change in largest tumour diameter on MRI (p?<?0.001). The AUC for the relative reduction in SUVmax on PET/CT was 0.78 (95 % CI 0.68–0.88), and for the relative reduction in tumour diameter at late enhancement on MRI was 0.79 (95 % CI 0.70–0.89). The AUC increased to 0.90 (95 % CI 0.83–0.96) in the final multivariate model with PET/CT, MRI and breast cancer subtype combined (p?=?0.012).

Conclusion

PET/CT and MRI showed comparable value for monitoring response during NAC. Combined use of PET/CT and MRI had complementary potential. Research with more patients is required to further elucidate the dependency on breast cancer subtype.     

18F-FDG PET/CT in HIV-related central nervous system pathology

Purpose

To evaluate the utility of ¹⁸F-FDG PET/CT in suspected cerebral pathology in HIV-infected individuals.

Methods

¹⁸F-FDG PET/CT scans from 29 HIV-infected individuals (29 brain scans, 22 whole-body scans) who presented with neurological symptoms and signs were retrospectively reviewed and compared with subsequent clinical investigations.

Results

The majority of patients (n?=?25) were referred to differentiate infection from malignant causes of cerebral pathology. Ten of the 11 patients with an eventual diagnosis of toxoplasmosis infection were correctly diagnosed by ¹⁸F-FDG PET/CT showing lesional uptake less than that of normal brain cortex (mean SUVmax 3.5, range 1.9 – 5.8). All five patients with a final diagnosis of primary central nervous system lymphoma (PCNSL) were correctly diagnosed by ¹⁸F-FDG PET/CT showing lesional uptake greater than that of normal brain cortex (mean SUVmax 18.8, range 12.4 – 29.9). Four of the five patients with ¹⁸F-FDG PET/CT features suggesting a vasculitic process had vasculitis confirmed as the final diagnosis. Three patients showed variable uptake in multiple cerebral lesions (including final diagnoses of tuberculosis and metastases from lung cancer in two patients) and there were four other miscellaneous diagnoses. In 12 patients biopsies were performed at sites guided by PET abnormality (7 brain, 5 lymph nodes) confirming or excluding significant disease in 11.

Conclusion

¹⁸F-FDG PET/CT is particularly useful for differentiating between infection and PCNSL in HIV-infected patients with a cerebral lesion on MRI or CT. ¹⁸F-FDG PET/CT was also a helpful tool in the diagnostic work-up of patients with other HIV-related cerebral pathology. Additional advantages of ¹⁸F-FDG PET/CT are the abilities to assess abnormally increased glucose metabolism in the body and to identify potential sites for biopsy.     

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

Aim

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

Materials and Methods

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

Results

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

Conclusion

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

     

Predictive value of <Superscript>18</Superscript>F-FDG PET/CT in restaging patients affected by ovarian carcinoma: a multicentre study

Purpose

Ovarian cancer is the eighth most common malignancy among women and has a high mortality rate. Prognostic factors able to drive an effective therapy are essential. ¹⁸F-Fluoro-2-deoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) has been investigated in patients with epithelial ovarian cancer and showed promise in diagnosing, staging, detecting recurrent lesions and monitoring treatment response. Conversely, its prognostic role remains unclear. We aimed at assessing the prognostic value of ¹⁸F-FDG PET/CT performed in the restaging process in a multicentre study.

Methods

We evaluated 168 patients affected by ovarian carcinoma, who underwent a restaging ¹⁸F-FDG PET/CT. The presence of local recurrences, lymph node involvement and distant metastasis was recorded as well as lesion dimensions, maximum and mean standardized uptake values (SUV_max and SUV_mean, respectively). Progression-free survival (PFS) and overall survival (OS) at 3 and 4 years were computed by using Kaplan-Meier curves. Increased odds ratio was assessed using Cox regression analysis testing all lesion parameters measured by PET/CT.

Results

PFS was significantly longer in patients with a negative than a positive restaging PET/CT study (3- and 4-year PFS 64 and 53 % vs 23 and 12 %, respectively; p?<?0.001). Similarly, a negative study was associated with a significantly higher OS rate after 4 years of follow-up (67 vs 25 % in negative and positive groups, respectively; p?<?0.001). Lymph node or distant involvement were also independently associated with an increased risk of disease progression [hazard ratio (HR) 1.6 and 2.2, respectively; p?=?0.003]. Moreover, PET/CT showed an incremental prognostic value compared to the International Federation of Gynecology and Obstetrics (FIGO) staging system. In the analysis of patient subsets, individuals with the same FIGO stage I–II but with negative PET had a significantly better 4-year OS than patients with low FIGO stage but positive PET. This implies that patients with the same FIGO stage can be further prognostically stratified using PET (p?=?0.01). At receiver-operating characteristic (ROC) analysis, no thresholds for semiquantitative parameters were predictive of a worse outcome.

Conclusion

¹⁸F-FDG PET/CT has an important prognostic value in assessing the risk of disease progression and mortality rate. An efficacious therapy planning might therefore effectively rely on ¹⁸F-FDG PET/CT findings. Semiquantitative data were not proven to be an effective tool to predict disease progression.

     

Assessment of tumor hypoxia by 62Cu-ATSM PET/CT as a predictor of response in head and neck cancer: a pilot study

Objective

In radiotherapy and chemotherapy tumor hypoxia is recognized as a major obstacle to effective treatment. We undertook a pilot study in patients with locally advanced head and neck cancer to determine whether there is a relationship between tumor uptake of ⁶²Cu-ATSM and response to chemoradiotherapy.

Methods

Seventeen patients were studied using PET/CT with ⁶²Cu-ATSM and ¹⁸F-FDG prior to the initiation of radiotherapy and chemotherapy. All patients had locally advanced head and neck cancer (stage III or IV). Tumor uptake in all patients was measured by region of interest analysis using the maximal standardized uptake value (SUVmax). A total dose of 50.4–70.2 Gy (median 70.2 Gy) was delivered in 29–39 fractions (median 39 fractions) to tumor. In patients with (non CR) and without (CR) residual/recurrent tumors at 2-year post irradiation, the statistical significance of the differences in tumor ⁶²Cu-ATSM SUVmax, T/M ratio, ¹⁸F-FDG SUVmax and tumor volume were analyzed using Student’s t test and Welch test. The relationship between clinical outcome and ⁶²Cu-ATSM/¹⁸F-FDG uptake patterns was analyzed using Kruskal–Wallis test. The correlation between SUVmax of ⁶²Cu-ATSM and ¹⁸F-FDG was compared by Spearman’s rank correlation test.

Results

Two of the 17 patients that were enrolled in our study were excluded from the final analysis. Of the 15 remaining patients, 9 patients were free of disease and 6 patients had residual/recurrent tumors. The SUVmax differed significantly (p < 0.05) between patients with or without residual/recurrent tumor on ⁶²Cu-ATSM PET/CT. Six of the 10 patients with tumors SUVmax >5.00 had residual/recurrent tumor, whereas all of the 5 patients with tumors SUVmax <5.00 were free of disease. There was no significant difference in FDG uptake between patients with and without residual/recurrent tumor.

Conclusions

The results of this pilot study suggested that ⁶²Cu-ATSM uptake may be a predictive indicator of tumor response to chemoradiotherapy in patients with locally advanced head and neck cancer.     

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 18F-FDG PET/CT for detection of suspected recurrence in patients with oesophageal carcinoma

Purpose

To evaluate the role of ¹⁸F-FDG PET/CT in the detection of recurrence in patients with oesophageal carcinoma, suspected clinically or following conventional investigations.

Methods

This was a retrospective study. Data from 180 patients (age 56.3?±?10.4 years; 126 men, 54 women) with histopathologically proven oesophageal carcinoma (squamous cell 115, adenocarcinoma 59, neuroendocrine carcinoma 4, small cell 1, poorly differentiated 1) who had undergone 227 ¹⁸F-FDG PET/CT studies for suspected recurrence were analysed. Recurrence was suspected clinically or following conventional investigations. PET/CT images were revaluated by two nuclear medicine physicians in consensus. Findings were grouped into local, nodal and distant recurrence. Results were compared to those from contrast-enhanced (CE) CT when available (109 patients). Clinical/imaging follow-up (minimum 6 months) with histopathology (when available) was taken as the reference standard.

Results

Of the 227 ¹⁸F-FDG PET/CT studies,166 were positive and 61 were negative for recurrent disease. PET/CT showed local recurrence in 134, nodal recurrence in 115 and distant recurrence in 47, with more than one site of recurrence in 34. The PET/CT findings were true-positive in 153 studies, true-negative in 54, false-positive in 13 and false-negative in 7. The sensitivity of ¹⁸F-FDG PET/CT was 96 %, the specificity was 81 %, the positive and negative predictive values were 92 % and 89 %, respectively, and the accuracy was 91 %. PET/CT showed similar accuracy in patients with squamous cell carcinoma and in those with adenocarcinoma (P?=?0.181).¹⁸F-FDG PET/CT was more specific than CECT (67 % vs. 21 %; P?<?0.0001). PET/CT was superior to CECT for the detection of nodal recurrence (P?<?0.0001), but not local recurrence (P?=?0.093) or distant metastases (P?=?0.441).

Conclusion

¹⁸F-FDG PET/CT shows high accuracy in the detection of suspected recurrence in patients with oesophageal carcinoma. It is more specific than and is superior to CECT in the detection of nodal recurrence.     

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.