Pretherapy metabolic tumour volume is an independent predictor of outcome in patients with diffuse large B-cell lymphoma

Purpose

We investigated the prognostic value of total metabolic tumour volume (TMTV) in diffuse large B-cell lymphoma (DLBCL).

Methods

TMTV was measured in 114 patients with newly diagnosed DLBCL who underwent ¹⁸F-FDG PET/CT at baseline before immunochemotherapy. TMTV was computed by summing the volumes of all lymphomatous lesions after applying the local SUVmax threshold of 41 % using semiautomatic software. Prognostic value was assessed by Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS).

Results

Median follow-up was 39 months. Average pretherapy TMTV was 509?±?568 cm³. The 3-year estimates of PFS were 77 % in the low metabolic burden group (TMTV ≤550 cm³) and 60 % in the high metabolic burden group (TMTV >550 cm³, p?=?0.04), and prediction of OS was even better (87 % vs. 60 %, p?=?0.0003). Cox regression showed independence of TMTV for OS prediction (p?=?0.002) compared with other pretherapy indices of tumour burden, such as tumour bulk and the International Prognostic Index.

Conclusion

Pretherapy TMTV is an independent predictor of outcome in patients with DLBCL.     

Baseline metabolic tumour volume is an independent prognostic factor in Hodgkin lymphoma

Purpose

The presence of a bulky tumour at staging in Hodgkin lymphoma (HL) is a predictor of a poor outcome. The total metabolic tumour volume at baseline (TMTV0) computed on PET may improve the evaluation of tumour burden. To explore the clinical usefulness of TMTV0, we compared the prognostic value of TMTV0, tumour bulk and interim PET response in a retrospective single-centre study.

Methods

From 2007 to 2010, 59 consecutive patients with a first diagnosis of HL were treated in our institution. PET was done at baseline (PET0) and after two cycles of chemotherapy (PET2), and treatment was not modified according to the PET2 result. TMTV0 was measured with a semiautomatic method using a 41 % SUVmax threshold. SUVmax reduction between PET0 and PET2 (ΔSUVmaxPET0-2) was also computed. Based on ROC analysis, patients with a ΔSUVmaxPET0-2 >71 % were considered good responders and a TMTV0 >225 ml was considered to represent hypermetabolic bulky disease.

Results

Median TMTV0 was 117 ml and 17 patients (29 %) had a TMTV0 >225 ml. TMTV0 (>225 ml vs. ≤225 ml) and tumour bulk (<10 cm vs. ≥10 cm) were predictive of 4-year PFS: 42 % vs. 85 % (p?=?0.001) and 44 % vs. 79 % (p < 0.03), respectively. In multivariate analysis, using ΔSUVmaxPET0-2, TMTV0 and bulky tumour as covariates, only ΔSUVmaxPET0-2 (p?=?0.0005, RR 6.3) and TMTV0 (p < 0.006, RR 4.4) remained independent predictors of PFS. Three prognosis groups were thus identified: ΔSUVmaxPET0-2 >71 % and TMTV0 ≤225 ml (n?=?37, 63 %), ΔSUVmaxPET0-2?=?<71 % or TMTV0 >225 ml (n?=?17, 29 %), and ΔSUVmaxPET0-2?=?<71 % and TMTV0 >225 ml (n?=?5, 8 %). In these three groups the 4-year PFS rates were 92 %, 49 %, and 20 % (p < 0.0001), respectively.

Conclusion

TMTV0 is more relevant than tumour bulk for predicting the outcome in patients with HL, and adds a significant prognostic insight to interim PET response assessment. The combination of TMTV0 and ΔSUVmaxPET0-2 made it possible to identify three subsets of HL patients with different outcomes. This may guide clinicians in their choice of therapeutic strategy.     

Variability of 18F-FDG-positive lung lesion volume by thresholding

Objectives

To assess the variability of ¹⁸F-FDG-positive volume measurements in lung cancer patients, obtained with different fixed percentages of maximum standard uptake value (SUVmax) thresholds.

Methods

PET dynamic acquisition involving ten frames was performed within 60–110 min post-injection in eight patients. In each lesion (n?=?11), volume was automatically outlined in each frame with fixed 40–50–60–70 % of the SUVmax thresholds. Thus, ten volume values for each threshold (V_{40–50–60–70}) were available to calculate relative SD (SDr), and hence relative measurement error (MEr) and repeatability (R). Dependence on SUVmax variability was also assessed.

Results

Mean SDr (<SDr>; %) of volume estimates was found to strongly correlate with threshold value (T; %): <SDr>?= 1.626?×?exp(0.044?×?T) (r?=?0.999; P?<?0.01). MEr and R for V₄₀ were found to be (95 % CL) 18.9 % and 26.7 %. For all fixed thresholds, in successive frames of an arbitrary lesion, volume estimate inversely correlated with SUVmax (P?≤?0.02).

Conclusions

A formula allows estimation of the variability of ¹⁸F-FDG-positive volumes provided by any fixed percentage of SUVmax threshold, and hence by any thresholding method. It only necessitates conversion of the threshold value into the SUVmax percentage in order to aid quick estimation of volume variability magnitude in current clinical practice.

Key Points

? In oncology, PET is widely used to assess the metabolic active volume ? This paper investigates the variability of ¹⁸ F-FDG-positive volumes by thresholding ? A formula is available for estimating this variability for any thresholding method ? For 40 %-SUVmax threshold, measurement error and repeatability are (95 % CL) 18.9 %/26.7 %     

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

Purpose

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

Methods

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

Results

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

Conclusion

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

Pretreatment metabolic tumour volume is predictive of disease-free survival and overall survival in patients with oesophageal squamous cell carcinoma

Purpose

It has been suggested that FDG PET has predictive value for the prognosis of treated oesophageal carcinoma. However, the studies reported in the literature have shown discordant results. The aim of this study was to determine whether pretherapy quantitative metabolic parameters correlate with patient outcomes.

Methods

Included in the study were 67 patients with a histological diagnosis of oesophageal squamous cell carcinoma. Each patient underwent ¹⁸F-FDG PET (4.5 MBq/kg) before chemoradiotherapy. Quantitative analysis was performed using the following parameters: age, weight loss, location, N stage, OMS performance status, MTV_p and MTV_p′ (metabolic tumour volume determined by two different physicians), MTV_40% (volume for a threshold of 40 % of SUVmax), MTV_a (volume automatically determined with a contrast-based adaptive threshold method), SUVmax, SUVmean and TLG (total lesion glycolysis).

Results

MTV_p and MTV_40% were highly correlated (Pearson’s index 0.92). SUVmean_p and SUVmean_40% were also correlated (Pearson’s index 0.86), as were TLG_p and TLG_40% (Pearson’s index 0.98). Similarly, the parameters obtained with the adaptive threshold method (MTV_a, SUVmean_a and TLG_a) were correlated with those obtained manually (MTV_p, SUVmean_p and TLG_p). The manual metabolic tumour volume determination (MTV_p and MTV_p′) was reproducible. Multivariate analysis for disease-free survival (DFS) showed that a larger MTV_p was associated with a shorter DFS (p?=?0.004) and that a higher SUVmax was associated with a longer DFS (p?=?0.02). Multivariate analysis for overall survival (OS) showed that a larger MTV_p was associated with a shorter OS (p?=?0.01) and that a tumour in the distal oesophagus was associated with a longer OS (p?=?0.005). The associations among the other parameters were not statistically significant.

Conclusion

Metabolic tumour volume is a major prognostic factor for DFS and OS in patients with oesophageal squamous cell carcinoma. Higher SUVmax values were paradoxically associated with longer survival. The location of the tumour also appeared to affect prognosis.     

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.     

Total lesion glycolysis by 18F-FDG PET/CT is a reliable predictor of prognosis in soft-tissue sarcoma

Purpose

Preoperative identification of aggressiveness is important for the establishment of a treatment strategy in patients with soft-tissue sarcoma (STS). We compared the predictive values of various metabolic parameters derived from PET/CT with ¹⁸F-FDG, including maximal standardized uptake value (SUVmax), total lesion glycolysis (TLG) and metabolic tumour volume (MTV).

Methods

A total of 66 patients with STS who had undergone FDG PET/CT before tumour resection were reviewed retrospectively. We determined SUVmax, TLG and MTV to compare their value in predicting disease progression, which was defined as local recurrence and metastases. Receiver operating characteristic curve (ROC) analysis was used to compare the accuracy. Univariate and multivariate analyses of conventional clinicopathological variables were used to compare the reliability of the metabolic parameters.

Results

TLG exhibited greater accuracy than SUVmax or MTV in ROC analysis (area under curve, AUC, 0.802, 0.726 and 0.681, respectively). The cut-off values for disease progression derived from the AUC data were TLG 250; SUVmax 6.0, and MTV 40 cm³. In univariate analysis, TLG (>250) was a more significant predictive factor than SUVmax and MTV (P?<?0.001, P?=?0.031 and P?=?0.022, respectively). TLG was the only meaningful metabolic parameter in the multivariate analysis (P?=?0.008) other than presence of metastasis at diagnosis (P?=?0.003).

Conclusion

TLG is a more accurate predictor of disease progression than SUVmax or MTV. TLG enables accurate preoperative assessment of aggressiveness comparable with conventional clinicopathological parameters.     

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

Purpose

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

Methods

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

Results

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

Conclusion

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

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

Purpose

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

Methods

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

Results

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

Conclusion

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

18F-FDG PET/CT for detection of malignant peripheral nerve sheath tumours in neurofibromatosis type 1: tumour-to-liver ratio is superior to an SUVmax cut-off

Objectives

To evaluate the usefulness of normalising intra-tumour tracer accumulation on ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to reference tissue uptake for characterisation of peripheral nerve sheath tumours (PNSTs) in neurofibromatosis type 1 (NF1) compared with the established maximum standardised uptake value (SUVmax) cut-off of >3.5.

Methods

Forty-nine patients underwent FDG PET/CT. Intra-tumour tracer uptake (SUVmax) was normalised to three different reference tissues (tumour-to-liver, tumour-to-muscle and tumour-to-fat ratios). Receiver operating characteristic (ROC) analyses were used out to assess the diagnostic performance. Histopathology and follow-up served as the reference standard.

Results

Intra-tumour tracer uptake correlated significantly with liver uptake (r _s ?=?0.58, P?=?0.016). On ROC analysis, the optimum threshold for tumour-to-liver ratio was >2.6 (AUC?=?0.9735). Both the SUVmax cut-off value of >3.5 and a tumour-to-liver ratio >2.6 provided a sensitivity of 100 %, but specificity was significantly higher for the latter (90.3 % vs 79.8 %; P?=?0.013).

Conclusions

In patients with NF1, quantitative ¹⁸F-FDG PET imaging may identify malignant change in neurofibromas with high accuracy. Specificity could be significantly increased by using the tumour-to-liver ratio. The authors recommend further evaluation of a tumour-to-liver ratio cut-off value of >2.6 for diagnostic intervention planning.

Key Points

? ¹⁸ F-FDG PET/CT is used for detecting malignancy in PNSTs in NF1 patients ? An SUV _max cut-off value may give false-positive results for benign plexiform neurofibromas ? Specificity can be significantly increased using a tumour-to-liver ratio     

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.     

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.     

18F-FDG PET/CT predicts survival in patients with inflammatory breast cancer undergoing neoadjuvant chemotherapy

Purpose

The objective of this study was to evaluate the role of ¹⁸F-FDG PET/CT in predicting overall survival in inflammatory breast cancer patients undergoing neoadjuvant chemotherapy.

Methods

Included in this retrospective study were 53 patients with inflammatory breast cancer who had at least two PET/CT studies including a baseline study before the start of neoadjuvant chemotherapy. Univariate and multivariate analyses were performed to assess the effects on survival of the following factors: tumor maximum standardized uptake value (SUVmax) at baseline, preoperatively and at follow-up, decrease in tumor SUVmax, histological tumor type, grade, estrogen, progesterone, HER2/neu receptor status, and extent of disease at presentation including axillary nodal and distant metastases.

Results

By univariate analysis, survival was significantly associated with decrease in tumor SUVmax and tumor receptor status. Patients with decrease in tumor SUVmax had better survival (P?=?0.02). Patients with a triple-negative tumor (P?=?0.0006), a Her2/neu-negative tumor (P?=?0.038) or an ER-negative tumor (P?=?0.039) had worse survival. Multivariate analysis confirmed decrease in tumor SUVmax and triple-negative receptor status as significant predictors of survival. Every 10 % decrease in tumor SUVmax from baseline translated to a 15 % lower probability of death, and complete resolution of tumor FDG uptake translated to 80 % lower probability of death (P?=?0.014). Patients with a triple-negative tumor had 4.11 times higher probability of death (P?=?0.004).

Conclusion

Decrease in tumor SUVmax is an independent predictor of survival in patients with inflammatory breast cancer undergoing neoadjuvant chemotherapy. Further investigation with prospective studies is warranted to clarify its role in assessing response and altering therapy.     

Tumor fragmentation estimated by volume surface ratio of tumors measured on 18F-FDG PET/CT is an independent prognostic factor of diffuse large B-cell lymphoma

Introduction

Our aim was to study the prognostic value of two new ¹⁸F-FDG PET biomarkers in diffuse large B-cell lymphoma (DLBCL). We examined the total tumor surface (TTS), describing the tumor–host interface, and the tumor volume surface ratio (TVSR), corresponding to the ratio between the total metabolic tumor volume (TMTV) and TTS, describing the tumor fragmentation.

Methods

We retrospectively included 215 patients with DLBCL. Patients underwent initial ¹⁸F-FDG PET/CT before R-CHOP (73%) or intensified R-CHOP (R-ACVBP) regimens (27%). The TMTV was measured using a fixed threshold value of 41% of SUVmax. To calculate TTS and TVSR, the surface was measured using an in-house software based on the marching cube algorithm. Spearman’s rank correlation coefficient (ρ) was computed between TMTV, TTS, and TVSR, and ROC analysis was performed. Survival functions at 5 years were studied using a Kaplan-Meier method and uni/multivariate Cox analysis.

Results

TVSR was poorly correlated with TMTV (ρ?=?0.5) and TTS (ρ?=?0.26), while TTS was highly correlated with TMTV (ρ?=?0.94) and was, therefore, excluded from the analysis. TMTV had the highest area under the ROC curve (0.711) and the best sensitivity (0.797), while TVSR had the best specificity (0.745). The optimal cut-off values to predict 5-year OS were 222 cm³ for TMTV and 6.0 cm for TVSR. Patients with high TMTV and TVSR had significantly worse prognosis in Kaplan-Meier and Cox univariate analysis. In a multivariate Cox analysis combining the International Prognostic Index (IPI), the type of chemotherapy, TMTV, and TVSR, all parameters were independent and significant prognostic factors (HR [95%CI]: IPI 1.4 [1.1-1.8], type of chemotherapy 4.5 [2.0-10.5], TMTV 2.8 [1.4-5.5], TVSR 2.1 [1.3-3.4]). A synergistic effect between TMTV and TVSR was observed in a Kaplan-Meier analysis combining the two parameters.

Conclusions

TVSR measured on the initial ¹⁸F-FDG PET is an independent prognostic factor in DLBCL and has an additional prognostic value when combined with TMTV, IPI score and chemotherapy.

     

Dynamic contrast-enhanced CT to assess metabolic response in patients with advanced non-small cell lung cancer and stable disease after chemotherapy or chemoradiotherapy

Objectives

To compare tumour enhancement patterns measured using dynamic contrast-enhanced (DCE)-CT with tumour metabolism measured using positron emission tomography (PET)-CT in patients with non-small cell lung cancer (NSCLC) and stable disease after chemotherapy or chemoradiotherapy.

Methods

After treatment, 75 NSCLC tumours in 65 patients who had stable disease on DCE-CT according to Response Evaluation Criteria in Solid Tumour (RECIST) were evaluated using PET-CT. On DCE-CT, relative enhancement ratios (RER) of tumour at 30, 60, 90, 120 s and 5 min after injection of contrast material were measured. Metabolic responses of tumours were classified into two groups according to the maximum standardized uptake value (SUVmax) by PET-CT: complete metabolic response (CR) with an SUVmax of less than 2.5, and noncomplete metabolic response (NR) with an SUVmax of at least 2.5.

Results

Using the optimal RER₆₀ cutoff value of 43.7 % to predict NR of tumour gave 95.7 % sensitivity, 64.2 % specificity, and 82.1 % positive and 95.0 % negative predictive values. After adjusting for tumour size, the odds ratio for NR in tumour with an RER₆₀ of at least 43.7 % was 70.85 (95 % CI?=?7.95–630.91; P?<?0.05).

Conclusions

Even when disease was stable according to RECIST, DCE-CT predicted hypermetabolic status of residual tumour in patients with NSCLC after treatment.

Key Points

? Dynamic contrast-enhanced CT (DCE-CT) can provide useful metabolic information about non-small cell lung cancer. ? NSCLC lesions, even grossly stable after treatment, show various metabolic states. ? DCE-CT enhancement patterns correlate with tumour metabolic status as shown by PET. ? DCE-CT helps to assess hypermetabolic NSCLC as stable disease after treatment.     

Locally advanced rectal cancer: diffusion-weighted MR tumour volumetry and the apparent diffusion coefficient for evaluating complete remission after preoperative chemoradiation therapy

Objective

To evaluate DW MR tumour volumetry and post-CRT ADC in rectal cancer as predicting factors of CR using high b values to eliminate perfusion effects.

Methods

One hundred rectal cancer patients who underwent 1.5-T rectal MR and DW imaging using three b factors (0, 150, and 1,000 s/mm²) were enrolled. The tumour volumes of T2-weighted MR and DW images and pre- and post-CRT ADC_150–1000 were measured. The diagnostic accuracy of post-CRT ADC, T2-weighted MR, and DW tumour volumetry was compared using ROC analysis.

Results

DW MR tumour volumetry was superior to T2-weighted MR volumetry comparing the CR and non-CR groups (P?<?0.001). Post-CRT ADC showed a significant difference between the CR and non-CR groups (P?=?0.001). The accuracy of DW tumour volumetry (A_z?=?0.910) was superior to that of T2-weighed MR tumour volumetry (A_z?=?0.792) and post-CRT ADC (A_z?=?0.705) in determining CR (P?=?0.015). Using a cutoff value for the tumour volume reduction rate of more than 86.8 % on DW MR images, the sensitivity and specificity for predicting CR were 91.4 % and 80 %, respectively.

Conclusion

DW MR tumour volumetry after CRT showed significant superiority in predicting CR compared with T2-weighted MR images and post-CRT ADC.

Key Points

? Diffusion-weighted MR (DWMR) imaging offers new information about rectal cancer. ? DWMR helps to predict complete remission after chemoradiotherapy in patients with advanced rectal cancer. ? DWMR provides more accurate diagnostic information than T2-weighted MRI. ? Apparent diffusion coefficients can predict CR, but they have certain clinical limitations.     

Fifteen different 18F-FDG PET/CT qualitative and quantitative parameters investigated as pathological response predictors of locally advanced rectal cancer treated by neoadjuvant chemoradiation therapy

Purpose

The aim of this study was to correlate qualitative visual response and various PET quantification factors with the tumour regression grade (TRG) classification of pathological response to neoadjuvant chemoradiotherapy (CRT) proposed by Mandard.

Methods

Included in this retrospective study were 69 consecutive patients with locally advanced rectal cancer (LARC). FDG PET/CT scans were performed at staging and after CRT (mean 6.7 weeks). Tumour SUVmax and its related arithmetic and percentage decrease (response index, RI) were calculated. Qualitative analysis was performed by visual response assessment (VRA), PERCIST 1.0 and response cut-off classification based on a new definition of residual disease. Metabolic tumour volume (MTV) was calculated using a 40 % SUVmax threshold, and the total lesion glycolysis (TLG) both before and after CRT and their arithmetic and percentage change were also calculated. We split the patients into responders (TRG 1 or 2) and nonresponders (TRG 3–5).

Results

SUVmax MTV and TLG after CRT, RI, ΔMTV% and ΔTLG% parameters were significantly correlated with pathological treatment response (p?<?0.01) with a ROC curve cut-off values of 5.1, 2.1 cm³, 23.4 cm³, 61.8 %, 81.4 % and 94.2 %, respectively. SUVmax after CRT had the highest ROC AUC (0.846), with a sensitivity of 86 % and a specificity of 80 %. VRA and response cut-off classification were also significantly predictive of TRG response (VRA with the best accuracy: sensitivity 86 % and specificity 55 %). In contrast, assessment using PERCIST was not significantly correlated with TRG.

Conclusion

FDG PET/CT can accurately stratify patients with LARC preoperatively, independently of the method chosen to interpret the images. Among many PET parameters, some of which are not immediately obtainable, the most commonly used in clinical practice (SUVmax after CRT and VRA) showed the best accuracy in predicting TRG.     

Dixon-based MRI for assessment of muscle-fat content in phantoms,healthy volunteers and patients with achillodynia: comparison to visual assessment of calf muscle quality

Objectives

To quantify the muscle fat-content (MFC) in phantoms, volunteers and patients with achillodynia using two-point Dixon-based magnetic resonance imaging (2pt-MRI_DIXON) in comparison to MR spectroscopy (MRS) and visual assessment of MFC.

Methods

Two-point Dixon-based MRI was used to measure the MFC of 15 phantoms containing 0-100 % fat-content and calf muscles in 30 patients (13 women; 57?±?15 years) with achillodynia and in 20 volunteers (10 women; 30?±?14 years) at 1.5 T. The accuracy of 2pt-MRI_DIXON in quantification of MFC was assessed in vitro using phantoms and in vivo using MRS as the standard of reference. Fat-fractions derived from 2pt-MRI_DIXON (FF_DIXON) and MRS (FF_MRS) were related to visual assessment of MFC (Goutallier grades 0–4) and Achilles-tendon quality (grade 0-4).

Results

Excellent linear correlation was demonstrated for FF_DIXON with phantoms and with FF_MRS in patients (p _c?=?0.997/0.995; p?<?0.001). FF_DIXON of the gastrocnemius muscle was significantly higher (p?=?0.002) in patients (7.0 %?±?4.7 %) compared with volunteers (3.6 %?±?0.7 %), whereas visual-grading showed no difference between both groups (p?>?0.05). FF_MRS and FF_DIXON were significantly higher in subjects with (>grade 1) structural damage of the Achilles-tendon (p?=?0.01).

Conclusions

Two-point Dixon-based MRI allows for accurate quantification of MFC, outperforming visual assessment of calf muscle fat. Structural damage of the Achilles tendon is associated with a significantly higher MFC.

Key points

? Two-point Dixon-based MRI allows accurate quantification of muscular fat content (MFC). ? Quantitative analysis outperforms visual analysis in the detection of elevated MFC. ? Achillodynia results in an increased MFC of the gastrocnemius muscles. ? Structural damage of the Achilles tendon further increases the MFC.     

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.