Displacement of the lumpectomy cavity defined by surgical clips and seroma based on 4D-CT scan for external-beam partial breast irradiation after breast-conserving surgery: a comparative study

Objective:

To compare the displacements of the lumpectomy cavity delineated by the surgical clips and the seroma based on four-dimensional CT (4D-CT) for external-beam partial breast irradiation (EB-PBI) after breast-conserving surgery (BCS).

Methods:

14 breast cancer patients after BCS were recruited for EB-PBI and undertook 4D-CT simulation. On the 10 sets of the 4D-CT images, all the surgical clips in the cavity were delineated. The gross tumour volume (GTV) formed by the clips, the seroma, and both the clips and the seroma were defined as GTV_c, GTV_s and GTV_c+s, respectively. The displacements of the centre of mass (COM) of the clips, GTV_c, GTV_s, GTV_c+s and the selected clips in the three-dimensional (3D) directions were recorded and compared.

Results:

In the left–right, anterior–posterior and superior–inferior directions, the displacements were 2.20, 1.80 and 2.70 mm for the clip COM; 0.90, 1.05 and 1.20 mm for GTV_c; 0.80, 1.05 and 0.80 mm for GTV_s; and 0.90, 1.20 and 1.40 mm for GTV_c+s, respectively. In the 3D directions, the displacements of the clip COM were greater than the GTV_c, GTV_s, GTV_c+s, and the displacements of the clip COM, GTV_c+s, GTV_c and GTV_s were significantly greater than the displacements of the selected clips (p<0.05).

Conclusion:

The displacements of the clip COM were greater than that of the GTV_c, GTV_s, GTV_c+s and the four selected clips. The optimal internal target volume should be defined based on the boundary displacements.

Advances in knowledge:

When the GTV was delineated using the clips and/or the seroma, there was displacement difference between the lumpectomy cavity centre and the boundary for the EB-PBI. The optimal internal target volume should be defined based on the boundary displacements of the lumpectomy cavity.Previous studies have reported that approximately 70–80% of the in-breast tumour recurrences occurred in the vicinity of the tumour bed (TB) and that the absolute risk of ipsilateral breast recurrence away from the primary tumour site is approximately 1.5–3.5% [1–4]. Thus, for early-stage breast cancer patients after breast-conserving surgery (BCS), partial breast irradiation (PBI), treating only the lumpectomy cavity with a suitable margin, may achieve a similar local control rate and an overall survival rate to whole-breast irradiation treating the whole breast. External-beam partial breast irradiation (EB-PBI) is an important approach in PBI, and clinical research has demonstrated that EB-PBI can achieve excellent results after strict patient selection and accurate target volume delineation [5,6].Accurate delineation of the TB is essential for EB-PBI [7]. Surgical clips and seroma were important surrogates in location and displacement measurement of the TB [8–10]. The optimal number of surgical clips, seroma clarity score (SCS), the delineation experience and contouring guidelines were important factors for TB delineation on CT images [10–14]. The target volume was typically defined using surgical clips, the seroma and any post-operative tissue changes when available [9]. The respiratory-induced displacements and set-up error were important components in EB-PBI planning, and the residual error was not >5 mm after online error correction based on cone-beam CT [15]. Therefore, respiratory-induced TB motion is the major component of the planning target volume for EB-PBI [8]. Four-dimensional CT (4D-CT) simulation has enabled CT data acquisition to be correlated with the respiratory cycle. Therefore, 4D-CT was pervasively used in delineating the target volume and forming the internal target volume (ITV) for EB-PBI [16,17].Although the displacements of the target volume delineated based on clips and seroma have been obtained using 4D-CT in prior studies [16,17], the displacement differences among target volumes have not been fully illustrated. In order to investigate the displacement differences among the target volumes delineated based on clips and/or seroma, we measured and compared the three-dimensional (3D) displacements among three target volumes, the centre of mass (COM) of all the surgical clips and four selected boundary clips during free-breathing (FB).     

18F-FDG PET/CT is Useful for Pretreatment Assessment of the Histopathologic Type of Thymic Epithelial Tumors

Purpose

This study was performed to assess the usefulness of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) or PET/computed tomography (CT) for distinguishing thymic epithelial tumors according to World Health Organization (WHO) classifications.

Methods

We analyzed a total of 45 patients (range, 29–75 years of age; mean, 55 years) with pathologically confirmed thymic epithelial tumors who underwent pretreatment ¹⁸F-FDG PET or PET/CT between November 2003 and October 2009. The size, visual grading of uptake value, peak standardized uptake value (SUVpeak), uptake pattern, and contour of each tumor, and associated findings on PET or PET/CT, were analyzed relative to the three simplified WHO subgroups: less-invasive thymomas (types A and AB), more-invasive thymomas (types B1, B2, and B3) and thymic carcinomas. We statistically assessed the relationship of ¹⁸F-FDG PET or PET/CT findings with these simplified subgroups.

Results

Of the 45 patients, ten had less-invasive thymomas, 23 had more-invasive thymomas, and 12 had thymic carcinomas. The SUVpeak of the less- and more-invasive thymomas were significantly lower than those of thymic carcinomas (p < 0.000), but there was no difference in SUVpeak between less- and more-invasive thymomas. The visual grading scale (p < 0.000), uptake pattern (p = 0.001), and contour (p < 0.000) of the tumors differed significantly among the three simplified subgroups.

Conclusion

The image findings of ¹⁸F-FDG PET or PET/CT differed significantly by histologic subgroups. Pre-treatment evaluation with ¹⁸F-FDG PET or PET/CT might be helpful in differentiating subgroups of thymic epithelial tumors.     

Impact of treatment planning with deformable image registration on dose distribution for carbon-ion beam lung treatment using a fixed irradiation port and rotating couch

Objective:

When using a fixed irradiation port, treatment couch rotation is necessary to increase beam angle selection. We evaluated dose variations associated with positional morphological changes to organs.

Methods:

We retrospectively chose the data sets of ten patients with lung cancer who underwent respiratory-gated CT at three different couch rotation angles (0°, 20° and −20°). The respective CT data sets are referred to as CT₀, CT₂₀ and CT₋₂₀. Three treatment plans were generated as follows: in Plan 1, all compensating bolus designs and dose distributions were calculated using CT₀. To evaluate the rotation effect without considering morphology changes, in Plan 2, the compensating boli designed using CT₀ were applied to the CT_±20 images. Plan 3 involved compensating boli designed using the CT_±20 images. The accumulated dose distributions were calculated using deformable image registration (DIR).

Results:

A sufficient prescribed dose was calculated for the planning target volume (PTV) in Plan 1 [minimum dose received by a volume ≥95% (D₉₅) > 95.8%]. By contrast, Plan 2 showed degraded dose conformation to the PTV (D₉₅ > 90%) owing to mismatch of the bolus design to the morphological positional changes in the respective CT. The dose assessment results of Plan 3 were very close to those of Plan 1.

Conclusion:

Dose distribution is significantly affected by whether or not positional organ morphology changes are factored into dose planning.

Advances in knowledge:

In treatment planning using multiple CT scans with different couch positions, it is mandatory to calculate the accumulated dose using DIR.The use of particle beam therapy is rapidly growing worldwide.¹ Some particle beam systems use a rotational gantry to allow irradiation from multiple directions. However, as the gantry for carbon-ion beam therapy is larger and heavier than that for proton beam therapy,² many carbon-ion beam treatment systems feature a fixed gantry with one or two beam ports placed at the sides of the treatment couch. The treatment couch is rotated around its long axis to allow beam entrance at oblique angles, eliminating the need for gantry rotation. It is necessary to consider changes in organ morphology when treating a patient with a fixed irradiation port and rotating couch. Usually, two or three treatment planning CT data sets are acquired at different couch rotation angles. Treatment planning parameters and patient accessories (patient collimators and compensating boli) are designed at each beam angle using the respective CT images acquired in the planned rotation positions. Deformable image registration (DIR)^3,4 is used to calculate the accumulated dose distribution from multiple beam directions using more than two CT data sets to factor in morphological changes of organs with treatment couch rotation. Compared with single planning CT, multiple planning CTs require extra time for clinical workflow both for CT acquisition and deformation planning. To date, however, patient and target dose variations owing to position-dependent morphological changes with treatment couch rotation have not been evaluated.Here, we evaluated patient and target dose variations owing to position-dependent morphological changes with treatment couch rotation.     

Retrocrural Lymph Node Metastasis Disclosed by 18F-FDG PET/CT: A Predictor of Supra-diaphragmatic Spread in Ovarian Cancer

Purpose

Retrocrural lymph nodes (RCLNs) communicate with retroperitoneal and posterior mediastinal LNs. It is possible that, when RCLNs are involved, supra-diaphragmatic extension will occur in abdomino-pelvic cancers. The authors investigated performance of ¹⁸F-FDG PET/CT to diagnose RCLN metastasis and whether RCLN metastases were associated with supra-diaphragmatic lymphatic metastases of ovarian cancer.

Materials and methods

Sixty-seven patients with stage IV ovarian cancer who had undergone ¹⁸F-FDG PET/CT were included in this retrospective study. Diagnostic performance of ¹⁸F-FDG PET/CT for RCLN metastasis was evaluated. Patients were divided into two groups by presence or absence of supra-diaphragmatic LN metastasis. The prevalences of RCLN metastasis between the two groups were compared and the odds ratio was calculated.

Results

Sensitivity and specificity of ¹⁸F-FDG PET/CT for RCLN metastasis were 96.3 and 100%, respectively. Of the 67 study subjects, 27 patients had RCLN metastases (40.3%). Fifty patients had supra-diaphragmatic LN metastases. ¹⁸F-FDG PET/CT showed 26 RCLN metastases in patients with supra-diaphragmatic LN metastases (54.5%), and only 1 in patients without supra-diaphragmatic LN metastasis (5.9%), and the difference between two groups was statistically significant (P < 0.05). The odds ratio that patients with RCLN metastasis would have supra-diaphragmatic LN metastasis was 17.3 (95% confidence interval = 2.1 to 140.9, P = 0.008).

Conclusion

Performance of ¹⁸F-FDG PET/CT to diagnose RCLN metastasis was excellent. RCLN metastasis revealed by ¹⁸F-FDG PET/CT was strongly associated with supra-diaphragmatic LN spread of ovarian cancer. Thus, RCLN metastasis could be used as a predictor of supra-diaphragmatic lymphatic metastasis of ovarian cancer.     

The value of intratumoral heterogeneity of 18F-FDG uptake to differentiate between primary benign and malignant musculoskeletal tumours on PET/CT

Objective:

The cumulative standardized uptake value (SUV)–volume histogram (CSH) was reported to be a novel way to characterize heterogeneity in intratumoral tracer uptake. This study investigated the value of fluorine-18 fludeoxyglucose (¹⁸F-FDG) intratumoral heterogeneity in comparison with SUV to discriminate between primary benign and malignant musculoskeletal (MS) tumours.

Methods:

The subjects comprised 85 pathologically proven MS tumours. The area under the curve of CSH (AUC-CSH) was used as a heterogeneity index, with lower values corresponding with increased heterogeneity. As 22 tumours were indiscernible on ¹⁸F-FDG positron emission tomography, maximum standardized uptake value (SUV_max), mean standardized uptake value (SUV_mean) and AUC-CSH were obtained in 63 positive tumours. The Mann–Whitney U test and receiver operating characteristic (ROC) analysis were used for analyses.

Results:

The difference between benign (n = 35) and malignant tumours (n = 28) was significant in AUC-CSH (p = 0.004), but not in SUV_max (p = 0.168) and SUV_mean (p = 0.879). The sensitivity, specificity and accuracy for diagnosing malignancy were 61%, 66% and 64% for SUV_max (optical threshold value, >6.9), 54%, 60% and 57% for SUV_mean (optical threshold value, >3) and 61%, 86% and 75% for AUC-CSH (optical threshold value, ≤0.42), respectively. The area under the ROC curve was significantly higher in AUC-CSH (0.71) than SUV_max (0.60) (p = 0.018) and SUV_mean (0.51) (p = 0.005).

Conclusion:

The heterogeneity index, AUC-CSH, has a higher diagnostic accuracy than SUV analysis in differentiating between primary benign and malignant MS tumours, although it is not sufficiently high enough to obviate histological analysis.

Advances in knowledge:

AUC-CSH can assess the heterogeneity of ¹⁸F-FDG uptake in primary benign and malignant MS tumours, with significantly greater heterogeneity associated with malignant MS tumours. AUC-CSH is more diagnostically accurate than SUV analysis in differentiating between benign and malignant MS tumours.     

Dosimetric benefits of hemigland stereotactic body radiotherapy for prostate cancer: implications for focal therapy

Objective:

Compared with standard, whole-gland (WG) therapies for prostate cancer, focal approaches may provide equivalent oncologic outcomes with fewer adverse effects. The purpose of this study was to compare organ-at-risk (OAR) dosimetry between hemigland (HG) and WG stereotactic body radiotherapy (SBRT) plans.

Methods:

Volumetric-modulated arc radiotherapy-based SBRT plans were designed to treat the left HG, right HG and WG in eight patients, using five fractions of 8 Gy. OARs of interest included the contralateral HG, rectum, urinary bladder, urethra, penile bulb and contralateral neurovascular bundle.

Results:

Rectal V_80% (the percentage of a normal structure receiving a dose of 80%) and V_90% were significantly lower with HG plans than with WG plans (median values of 4.4 vs 2.5 cm³ and 2.1 vs 1.1 cm³, respectively, p < 0.05 by Student''s t-test). Bladder V_50% was also reduced significantly in HG plans (32.3 vs 17.4 cm³, p < 0.05), with a trend towards reduction of V_100% (3.4 vs 1.3 cm³, p = 0.09). Urethral maximum dose and mean doses to the penile bulb and contralateral neurovascular bundle were also reduced significantly (42.0 vs 39.7 Gy, p < 0.00001; 13.3 vs 9.2 Gy, p < 0.05; and 40.2 vs 19.3 Gy, p < 0.00001, respectively).

Conclusion:

Targeting an HG volume rather than a WG volume when delivering SBRT can offer statistically significant reductions for all OARs. Given the large magnitude of the reduction in dose to these OARs, it is anticipated that HG SBRT could offer a superior toxicity profile when compared with WG SBRT. This is likely to be most relevant in the context of salvaging a local failure after radiation therapy.

Advances in knowledge:

The dosimetric feasibility of HG SBRT is demonstrated. When compared with WG SBRT plans, the HG plans demonstrate statistically significant and large magnitude reduction in doses to the rectum, bladder, urethra, penile bulb and contralateral neurovascular bundle, suggesting the possibility of improved toxicity outcomes with HG SBRT. This is likely to be most relevant in the context of salvaging a local failure after radiation therapy.     

Validation of Simple Quantification Methods for 18F-FP-CIT PET Using Automatic Delineation of Volumes of Interest Based on Statistical Probabilistic Anatomical Mapping and Isocontour Margin Setting

Purpose

¹⁸F-FP-CIT positron emission tomography (PET) is an effective imaging for dopamine transporters. In usual clinical practice, ¹⁸F-FP-CIT PET is analyzed visually or quantified using manual delineation of a volume of interest (VOI) for the striatum. In this study, we suggested and validated two simple quantitative methods based on automatic VOI delineation using statistical probabilistic anatomical mapping (SPAM) and isocontour margin setting.

Methods

Seventy-five ¹⁸F-FP-CIT PET images acquired in routine clinical practice were used for this study. A study-specific image template was made and the subject images were normalized to the template. Afterwards, uptakes in the striatal regions and cerebellum were quantified using probabilistic VOI based on SPAM. A quantitative parameter, Q_SPAM, was calculated to simulate binding potential. Additionally, the functional volume of each striatal region and its uptake were measured in automatically delineated VOI using isocontour margin setting. Uptake-volume product (Q_UVP) was calculated for each striatal region. Q_SPAM and Q_UVP were compared with visual grading and the influence of cerebral atrophy on the measurements was tested.

Results

Image analyses were successful in all the cases. Both the Q_SPAM and Q_UVP were significantly different according to visual grading (P < 0.001). The agreements of Q_UVP or Q_SPAM with visual grading were slight to fair for the caudate nucleus (κ = 0.421 and 0.291, respectively) and good to perfect to the putamen (κ = 0.663 and 0.607, respectively). Also, Q_SPAM and Q_UVP had a significant correlation with each other (P < 0.001). Cerebral atrophy made a significant difference in Q_SPAM and Q_UVP of the caudate nuclei regions with decreased ¹⁸F-FP-CIT uptake.

Conclusion

Simple quantitative measurements of Q_SPAM and Q_UVP showed acceptable agreement with visual grading. Although Q_SPAM in some group may be influenced by cerebral atrophy, these simple methods are expected to be effective in the quantitative analysis of ¹⁸F-FP-CIT PET in usual clinical practice.     

18F-FDG Uptake of Human Testis on PET/CT: Correlation with Age,Sex Hormones,and Vasectomy

Purpose

The purpose of this study was to evaluate glucose metabolism of normal human testis on ¹⁸F-FDG PET/CT and to assess possible correlations among age, the serum levels of sex hormones, and vasectomy.

Methods

¹⁸F-FDG PET/CT was performed in 66 normal healthy men (50.8 ± 13.6 years, range 22–81), and mean standard uptake values (SUV) of ¹⁸F-FDG in testis and adductor muscle were measured. Testis-muscle SUV ratios (T/M ratios) were calculated. Serum levels of total testosterone, free testosterone, estradiol, and of sex-hormone binding globulin (SHBG) were measured. We searched for correlations between T/M ratios and age and the serum concentrations of sex hormones. ¹⁸F-FDG PET/CT was also performed in 32 vasectomized men (55.7 ± 7.8 years, range 38–71) and 52 nonvasectomized men (55.4 ± 11.6 years, range 37–72). Mean SUVs of testis and adductor muscle were measured, and T/M ratios were calculated.

Results

A significant age-related decline was found in T/M ratio (r = −0.509, p < 0.0001). Serum levels of total testosterone and free testosterone were also found to be positively correlated with T/M ratio (r = 0.427, p = 0.0003; r = 0.435, p = 0.0003, respectively). The mean SUV and T/M ratio of vasectomized men were significantly lower than those of nonvasectomized men (p < 0.0378 and p = 0.0001, respectively).

Conclusions

Glucose metabolism in the testis in an adult population was found to be correlated with age, serum sex hormone level, and vasectomy history. These results indicate that testicular ¹⁸F-FDG uptake may have attributed to testicular function and testicular histology. Our findings may have important implications for the interpretation of testicular ¹⁸F-FDG uptake in the normal adult population.     

Computed diffusion-weighted MRI for prostate cancer detection: the influence of the combinations of b-values

Objective:

To evaluate the influence of the combinations of b-values on computed diffusion-weighted images (cDWIs) for prostate cancer (PCa) detection at b = 2000 s mm⁻².

Methods:

Diffusion-weighted imaging (DWIs) for 31 patients with PCa (65.2 ± 7.1 years) were obtained pre-operatively at different b-values (0, 100, 500, 1000 and 2000 s mm⁻²) on a 3-T MRI. cDWIs at b = 2000 were generated by using six b-value combinations: 0–100 s mm⁻² (cDWI_0–100); 0–500 s mm⁻² (cDWI_0–500); 100–500 s mm⁻² (cDWI_100–500); 0–1000 s mm⁻² (cDWI_0–1000); 100–1000 s mm⁻² (cDWI_100–1000); and 500–1000 s mm⁻² (cDWI_500–1000). These cDWIs and measured DWIs with b = 2000 s mm⁻² (mDWI₂₀₀₀) were evaluated in this setting. To assess image quality for each DWI, contrast ratios (CRs) of cancerous and non-cancerous lesions were evaluated. To compare the detectability of PCa for each DWI, receiver operating characteristic analysis was used.

Results:

CRs of all cDWIs were significantly higher than those of mDWI₂₀₀₀ (p < 0.05). Areas under the curve of cDWI_0–100 (0.62) and cDWI_0–500 (0.65) were significantly smaller (p < 0.05) than those of others (cDWI_100–500, 0.72; cDWI_0–1000, 0.73; cDWI_100–1000, 0.71; cDWI_500–1000, 0.74; mDWI₂₀₀₀, 0.72).

Conclusion:

The combinations of b-values influenced image quality and diagnostic ability of cDWIs for PCa detection. The combinations of b ≥ 100 and b ≥ 500 s mm⁻², as well as b = 0 and b = 1000 s mm⁻², were optimal in this study.

Advances in knowledge:

For generating the useful cDWI for PCa detection, radiologists should take care of the combination of b-values when including low b-values.Diffusion-weighted imaging (DWI) and MRI are now being widely used in body cancer imaging for detection, characterization and assessment of treatment response.^1–3 Prostate cancer (PCa) detection is sometimes difficult because of the high background signal of parenchyma due to the presence of hypertrophy, bleeding and inflammation.Therefore, for better cancer detection with DWI, the focus should be on contrast in signal intensity (SI) between cancer and normal parenchyma.^4,5 It has recently been reported that DWI obtained with ultrahigh b-values provide good contrast between cancerous and background tissue for better PCa detection.^6–8 Furthermore, two studies in particular have demonstrated the advantage of DWI obtained with a b-value of 2000 s mm⁻² rather than with 1000 s mm⁻² for PCa diagnosis using either 1.5- or 3.0-T MR systems.^8,9 These studies found that the background tissue signal on DWI obtained with 2000 s mm⁻² is more suppressed and the contrast between signals of cancerous and non-cancerous lesions thus more enhanced than on DWI obtained with 1000 s mm⁻². Although images obtained with b-values >1000 s mm⁻² are clinically preferable, they are more difficult to obtain in practice because of certain disadvantages such as poor signal-to-noise ratio (SNR) and potential eddy current distortions resulting from the large diffusion-sensitizing gradients used.Computed DWI (cDWI) is a recently introduced computational technique that can produce any b-value images from DWI acquired with at least two different b-values.^10–12 Blackledge et al have proved that the cDWI technique allows higher b-value images to be obtained with a good SNR because it can suppress background noise while maintaining the original lesion signal. Furthermore, cDWI generated at b = 2000 s mm⁻² from DWI obtained with b = 0 and 1000 s mm⁻² reportedly attained a better contrast ratio (CR) between cancerous and non-cancerous lesions than did an actual DWI measured with b = 2000 s mm⁻² and showed a detection ability for PCa comparable to that of an actual DWI measured with b = 2000 s mm⁻².¹³ However, it remains unclear which combination of b-values is optimal for generating cDWI with a high b-value such as 2000 s mm⁻² for detection of PCa in routine clinical practice. The aim of our study was therefore to evaluate the influence of the combinations of b-values on cDWI at b = 2000 s mm⁻² for PCa detection and to determine the optimal combination on a 3-T MR system.     

Staging accuracy of pancreatic cancer: Comparison between non-contrast-enhanced and contrast-enhanced PET/CT

Purpose

Our aim was to clarify the diagnostic impact of contrast-enhanced (CE) ¹⁸F-fluorodeoxyglucose (FDG)–positron emission tomography (PET)/computed tomography (CT) for staging of pancreatic cancer compared to non-CE PET/CT.

Method and materials

Between April 2006 and November 2009, a total of 95 patients (age range, 36–83 years [mean age, 67]) with primary pancreatic cancer underwent ¹⁸F-FDG PET/CT examinations. Diagnostic accuracy was compared between non-CE PET/CT and CE PET/CT. Images were analyzed visually and quantitatively by two blinded reviewers. Reference standard was histological examination in 48 patients (51%) and/or confirmation of an obvious progression in number and/or size of the lesions on follow-up CT examinations in 47 patients (49%).

Results

For T-staging, invasion of duodenum (n = 20, 21%), mesentery (n = 12, 13%), and retroperitoneum (n = 13, 14%) was correctly diagnosed by both modalities. The ROC analyses revealed that the Az values of celiac artery (CA), common hepatic artery (CHA), splenic artery (SV), and superior mesenteric vein (SMV) invasion were significantly higher in the CE PET/CT group for both readers. Nodal metastasis was correctly diagnosed by CE PET/CT in 38 patients (88%) and by non-CE PET/CT in 45 patients (87%). Diagnostic accuracies of nodal metastasis in two modalities were similar. Using CE PET/CT, distant metastasis, scalene node metastasis, and peritoneal dissemination were correctly assigned in 39 patients (91%), while interpretation based on non-CE PET/CT revealed distant metastasis, scalene node metastasis, and peritoneal dissemination in 42 patients (81%). Diagnostic accuracy of distant metastasis, scalene node metastasis, and peritoneal dissemination with CE PET/CT was significantly higher than that of non-CE PET/CT (p < 0.05).

Conclusion

CE PET/CT allows a more precise assessment of distant metastasis, scalene node metastasis, and peritoneal dissemination in patients with pancreatic cancer.     

Prognostic Significance of Volume-based Metabolic Parameters by 18F-FDG PET/CT in Gallbladder Carcinoma

Purpose

We investigated the prognostic values of volume-based metabolic parameters by ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) in gallbladder carcinoma patients and compared them with other prognostic parameters.

Materials and Methods

We enrolled 44 patients, who were initially diagnosed with gallbladder carcinoma and undergoing ¹⁸F-FDG PET/CT. Various metabolic volume-based PET parameters of primary tumors, including maximum and average standardized uptake values (SUV_max, SUV_avg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), were measured in gallbladder carcinoma patients using mediastinal blood pool activity as a threshold SUV for determining the tumor boundaries. Overall survival analysis was performed using the Kaplan-Meier method with PET parameters and other clinical variables. For determining independent prognostic factors, Cox proportional hazards regression analysis was performed.

Results

Of the 44 enrolled patients, cancer- or treatment-related death occurred in 30 (68.2 %). The mean clinical follow-up period was 22.2 ± 10.4 m (range, 0.6-35.9 m). Univariate analysis demonstrated that clinical or pathologic TNM stage (P < 0.001), treatment modality (P < 0.001), MTV (cutoff = 135 cm³, P = 0.001), and TLG (cutoff = 7,090, P < 0.05) were significant prognostic factors. In multivariate analysis, both clinical or pathologic TNM stage [hazard ratio (HR) = 2.019 (I vs II), 21.287 (I vs III), and 24.354 (I vs IV); P = 0.001) and TLG (HR = 2.930; P < 0.05) were independent prognostic factors for predicting overall survival.

Conclusions

In gallbladder cancer, TLG of the primary tumor, a volume-based metabolic parameter, is a significant independent prognostic factor for overall survival in conjunction with the clinical or pathological TNM stage.     

Dosimetric effects of roll rotational setup errors on lung stereotactic ablative radiotherapy using volumetric modulated arc therapy

Objective:

To evaluate the dosimetric effects of roll-rotational setup errors of stereotactic ablative radiotherapy (SABR) for lung cancer using volumetric modulated arc therapy (VMAT).

Methods:

A total of 23 lung SABR cases were evaluated retrospectively. Each of the planning CT images was intentionally rotated by ±1°, ±2° and ±3°. After that, to simulate the translational couch correction, rotated CT images were moved along the x, y and z axis to match the centroid of the target volume in the rotated CT images with that in the original CT images. The differences in D_95% and V_100% of the target volume, D_0.35cc of spinal cord, D_0.35cc and D_5cc of oesophagus and V_20Gy of lung between the original and the rotated CT images were calculated.

Results:

The average differences in D_95% and V_100% of target volume, D_0.35cc of spinal cord, D_0.35cc and D_5cc of oesophagus and V_20Gy of lung were −0.3% ± 0.4% and −0.7% ± 2.4%, 1.6 ± 27.9 cGy, −1.6 ± 37.6 cGy, 15.9 ± 25.3 cGy and 0.0% ± 0.1%, respectively. The dosimetric changes in organs at risk (OARs) near the target volume were sometimes considerable due to roll-rotational setup errors, despite the translational correction, and those were patient specific.

Conclusion:

In the case of coplanar VMAT for lung SABR, dosimetric changes to the target volume due to roll-rotational setup errors could be compensated by translational correction, whereas those to the OARs could not in some cases.

Advances in knowledge:

Roll-rotational setup errors would increase the dose to OARs despite the translational correction.     

Diagnostic Performance of 68Ga-DOTATATE PET/CT, 18F-FDG PET/CT and 131I-MIBG Scintigraphy in Mapping Metastatic Pheochromocytoma and Paraganglioma

Purpose

To evaluate the diagnostic performance of ⁶⁸Ga-DOTATATE ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT), ¹⁸F-FDG PET/CT and ¹³¹I-MIBG scintigraphy in the mapping of metastatic pheochromocytoma and paraganglioma.

Materials and Methods

Seventeen patients (male = 8, female = 9; age range, 13–68 years) with clinically proven or suspicious metastatic pheochromocytoma or paraganglioma were included in this prospective study. Twelve patients underwent all three modalities, whereas five patients underwent ⁶⁸Ga-DOTATATE and ¹³¹I-MIBG without ¹⁸F-FDG. A composite reference standard derived from anatomical and functional imaging findings, along with histopathological information, was used to validate the findings. Results were analysed on a per-patient and on per-lesion basis. Sensitivity and accuracy were assessed using McNemar’s test.

Results

On a per-patient basis, 14/17 patients were detected in ⁶⁸Ga-DOTATATE, 7/17 patients in ¹³¹I-MIBG, and 10/12 patients in ¹⁸F-FDG. The sensitivity and accuracy of ⁶⁸Ga-DOTATATE, ¹³¹I-MIBG and ¹⁸F-FDG were (93.3 %, 94.1 %), (46.7 %, 52.9 %) and (90.9 %, 91.7 %) respectively. On a per-lesion basis, an overall of 472 positive lesions were detected; of which 432/472 were identified by ⁶⁸Ga-DOTATATE, 74/472 by ¹³¹I-MIBG, and 154/300 (patient, n = 12) by ¹⁸F-FDG. The sensitivity and accuracy of ⁶⁸Ga-DOTATATE, ¹³¹I-MIBG and ¹⁸F-FDG were (91.5 %, 92.6 % p < 0.0001), (15.7 %, 26.0 % p < 0.0001) and (51.3 %, 57.8 % p < 0.0001) respectively. Discordant lesions were demonstrated on ⁶⁸Ga-DOTATATE, ¹³¹I-MIBG and ¹⁸F-FDG.

Conclusions

Ga-DOTATATE PET/CT shows high diagnostic accuracy than ¹³¹I-MIBG scintigraphy and ¹⁸F-FDG PET/ CT in mapping metastatic pheochromocytoma and paraganglioma.     

Clinical Significance of Diffuse 18F-FDG Uptake in Residual Thyroid Gland after Unilateral Thyroid Lobectomy

Purpose

We investigated the clinical significance of diffuse uptake in remaining thyroid after unilateral lobectomy for thyroid cancer.

Methods

A total of 144 thyroid cancer patients who underwent ¹⁸F-FDG PET/CT after lobectomy were enrolled in the present study. The PET/CT images were evaluated for the presence of diffuse ¹⁸F-FDG uptake with maximum SUV (SUVmax) >2.0 in the residual thyroid and placed into one of two groups: with diffuse uptake and without diffuse uptake group. Clinical, laboratory, and PET/CT parameters in both groups were compared. Correlations between SUVmax of thyroid and available parameters were analyzed.

Results

Forty-two of 144 patients (29.2%) had diffuse thyroid uptake (mean SUVmax: 3.2 ± 1.1). All patients with diffuse uptake and 96 (94.1%) without diffuse uptake were receiving thyroxine therapy (P = 0.09). Thyroid function tests showed that most patients were euthyroid status (78.6 vs. 85.3%, P = 0.36). TgAb levels were significantly higher in patients with diffuse uptake (338.0 ± 664.6 vs. 57.3 ± 46.4, P < 0.0001). Mean attenuation values in the diffuse uptake group were significantly lower (72.2 ± 15. vs. 97.0 ± 16.0, P < 0.0001). An inverse correlation was found between SUVmax and mean attenuation values of residual thyroid in all patients (r = −0.57, P < 0.0001) and subgroup with diffuse uptake (r = −0.31, P < 0.05).

Conclusion

In this study, diffuse ¹⁸F-FDG uptake in the residual thyroid after unilateral lobectomy was a relatively frequent finding and may be associated with chronic thyroiditis. This uptake is not influenced by thyroid status or thyroxine therapy. The ¹⁸F-FDG uptake is inversely correlated with mean attenuation value of thyroid.     

Predictors of late bowel toxicity using three different methods of contouring in patients undergoing post-operative radiation for cervical cancer

Objective:

This study investigates the correlation between dose–volume histogram derived from three bowel contouring methods and late toxicity in patients undergoing post-operative radiation therapy (PORT) for cervical cancer.

Methods:

From June 2010 to May 2013, 103 patients undergoing PORT were included. Three different contouring methods were used: (a) individual small bowel (SB) and large bowel (LB) loops, (b) total bowel (TB; including SB and LB) and (c) peritoneal cavity (PC). The volume of SB, LB, TB and PC receiving 15, 30 and 40 Gy was calculated. Acute and late bowel toxicities were scored using Common Terminology Criteria for Adverse events v. 3.0. Receiver operating characteristic curve identified thresholds predicting late toxicity with the highest specificity. All data were dichotomized across these thresholds. Univariate and multivariate analyses were performed using SPSS^® v. 20 (IBM Corporation, Armonk, NY; formerly SPSS Inc., Chicago, IL).

Results:

On univariate analysis, V₃₀ PC ≥ 900 cm³ (p = 0.01), V₄₀ PC ≥ 750 cm³ (p = 0.03) and V₄₀ TB ≥ 280 cm³ (p = 0.03) and use of concurrent chemotherapy (p = 0.03) predicted grade ≥II acute toxicity. On multivariate analysis, use of concurrent chemotherapy [odds ratio (OR) 3.5, 95% confidence interval (CI) 1.1–11.1, p = 0.03] and V₃₀ PC ≥ 900 cm³ (OR 2.3, 95% CI 1–5.5, p = 0.05) predicted acute grade ≥II toxicity. On univariate analysis for late toxicity, SB (V₃₀ ≥ 190 cm³, p = 0.009; V₄₀ ≥ 150 cm³, p = 0.03), LB (V₁₅ ≥ 250 cm³, p = 0.04), V₄₀ PC (V₄₀ ≥ 750 cm³, p = 0.001) and presence of acute grade ≥III toxicity (p = 0.006), treatment technique (three-dimensional conformal radiation or intensity modulated radiotherapy, p = 0.02) predicted more than or equal to grade ll late bowel toxicity. On multivariate analysis, only body mass index ≥25 kg m⁻² (OR 7.3, 95% CI 1.6–31.6, p = 0.008) and presence of acute grade III toxicity predicted toxicity (OR 5.1, 95% CI 1.4–18.1, p = 0.007).

Conclusion:

V₃₀ PC ≥ 900 cm³ and use of concurrent chemotherapy independently predicts acute toxicity. Presence of acute grade ≥III toxicity independently predicts late toxicity. Minimizing dose to PC subvolumes can therefore reduce both acute and late toxicities.

Advances in knowledge:

Study establishes PC thresholds that can minimize both acute and late bowel toxicities.     

Assessment of outcomes with delayed 18F-FDG PET-CT response assessment in head and neck squamous cell carcinoma

Objective:

To assess the accuracy of a 4-month post-(chemo)radiotherapy 18-fludeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)-CT for head and neck squamous cell carcinoma (HNSCC).

Methods:

105 patients who underwent a baseline and response assessment ¹⁸F-FDG PET-CT scan between 2008 and April 2013 were identified. ¹⁸F-FDG PET-CT outcomes were analysed with reference to clinicopathological outcomes.

Results:

79 of 105 (75%) ¹⁸F-FDG PET-CT scans demonstrated a complete metabolic response; 19 of 101 (19%) for assessable primary tumours were positive; and 19 of 93 (20%) for patients with nodal disease were equivocal (n = 10) or positive (n = 9). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for primary and nodal disease were 90%, 89%, 47%, 99% and 91%, 89%, 53% and 99%, respectively. Eight of nine patients with a positive nodal response scan had clinicopathological evidence of residual nodal disease (PPV, 89%). 2 of 10 patients with equivocal nodal responses had clinicopathological evidence of residual nodal disease (PPV, 20%).

Conclusion:

¹⁸F-FDG PET-CT 4 months post treatment has a very high NPV. A positive ¹⁸F-FDG PET-CT has a high PPV for residual nodal disease. By contrast, patients who have an equivocal nodal response have a low PPV.

Advances in knowledge:

Response assessment ¹⁸F-FDG PET-CT is a valuable tool in guiding the selective use of neck dissection following (chemo)radiotherapy for HNSCC. An equivocal lymph node response has a limited predictive value for persistent disease, and optimal management remains a clinical challenge.     

A comparison of high b-value vs standard b-value diffusion-weighted magnetic resonance imaging at 3.0?T for medulloblastomas

Objective:

To investigate the utility of diffusion-weighted (DW) MRI using high b-value vs standard b-value for patients with medulloblastoma (MB). Minimum apparent diffusion coefficient (ADC_MIN) values were also compared with tumour cellularity.

Methods:

High and standard b-value DW images were obtained for 17 patients with MB. The number and location of the lesions, signal intensities (SIs), signal-to-noise ratios (SNRs), contrast-to-noise ratios, contrast ratios (CRs) and ADCs of the lesions were compared. Tumour cellularity was also measured and compared with ADC_MIN values.

Results:

All 20 lesions were hyperintense on the DW MR images with high and standard b-values. Four additional lesions were revealed on high b-value, and all 24 lesions were more conspicuous at high b-value. SI, SNR and ADC values for the lesions were lower in the high b-value images than in the standard b-value images. The ADC_MIN value at b = 3000 s mm⁻² was more significantly associated with tumour cellularity than that at b = 1000 s mm⁻². CR values were significantly higher in the high b-value images than in the standard b-value images.

Conclusion:

DW imaging using high b-value may be beneficial for detecting additional, less prominent lesions and may improve the contrast between MB lesions and normal tissue. A stronger inverse correlation with tumour cellularity was identified using the ADC_MIN values at high b-value.

Advances in knowledge:

This study demonstrates the superiority of high b-value DW imaging compared with standard b-value imaging for the detection of MB lesions, especially those with subtle foci.     

Reproducibility of 18F-FDG PET uptake measurements in head and neck squamous cell carcinoma on both PET/CT and PET/MR

Objective:

To investigate reproducibility of fluorine-18 fludeoxyglucose (¹⁸F-FDG) uptake on ¹⁸F-FDG positron emission tomography (PET)/CT and ¹⁸F-FDG PET/MR scans in patients with head and neck squamous cell carcinoma (HNSCC).

Methods:

30 patients with HNSCC were included in this prospective study. The patients were scanned twice before radiotherapy treatment with both PET/CT and PET/MR. Patients were scanned on the same scanners, 3 days apart and according to the same protocol. Metabolic tumour activity was measured by the maximum and peak standardized uptake value (SUV_max and SUV_peak, respectively), and total lesion glycolysis from the metabolic tumour volume defined from ≥50% SUV_max. Bland–Altman analysis with limits of agreement, coefficient of variation (CV) from the two modalities were performed in order to test the reproducibility. Furthermore, CVs from SUV_max and SUV_peak were compared. The area under the curve from cumulative SUV–volume histograms were measured and tested for reproducibility of the distribution of ¹⁸F-FDG uptake.

Results:

24 patients had two pre-treatment PET/CT scans and 21 patients had two pre-treatment PET/MR scans available for further analyses. Mean difference for SUV_max, peak and mean was approximately 4% for PET/CT and 3% for PET/MR, with 95% limits of agreement less than ±20%. CV was small (5–7%) for both modalities. There was no significant difference in CVs between PET/CT and PET/MR (p = 0.31). SUV_max was not more reproducible than SUV_peak (p = 0.09).

Conclusion:

¹⁸F-FDG uptake in PET/CT and PET/MR is highly reproducible and we found no difference in reproducibility between PET/CT and PET/MR.

Advances in knowledge:

This is the first report to test reproducibility of PET/CT and PET/MR.Functional imaging with fluorine-18 fludeoxyglucose positron emission tomography combined with CT (¹⁸F-FDG PET/CT) has been shown to be useful for prognostication of head and neck squamous cell carcinoma (HNSCC),^1–3 and the use of ¹⁸F-FDG PET/CT has also been shown to reduce interobserver variability in target delineation for radiotherapy.^4,5 Furthermore, ¹⁸F-FDG PET/CT can identify regions of the tumour with a high risk of relapse, leading to the idea that ¹⁸F-FDG uptake might be a target for dose painting.^6,7 Finally, ¹⁸F-FDG PET/CT may be used in response evaluation.^8,9 Maximum standardized uptake value (SUV_max) has for many years been the main uptake measurement in prognostic studies for various malignancies. More recent studies have focused on demonstrating prognostic value of PET/CT-based volumetric parameters such as metabolic tumour volume (MTV) and total lesion glycolysis (TLG). MTV is the sum of the volume of voxels with standard uptake value (SUV) exceeding a certain threshold value in a tumour, and TLG is calculated by multiplying MTV and the mean standardized uptake value (SUV_mean) of the MTV. These volume-based PET parameters have increasingly gained interest and have been reported to be significant prognostic factors for various malignancies including HNSCC.^{10–13 18}F-FDG PET/CT is currently not routinely recommended as a diagnostic tool in HNSCC except in very specific situations,¹⁴ but reproducibility of the ¹⁸F-FDG signal is a prerequisite for a more widespread use of ¹⁸F-FDG PET for the above-mentioned indications. Yet, only a few studies of the reproducibility of ¹⁸F-FDG PET/CT exist^8,15–21 and none of these studies includes patients with HNSCC.MRI is gaining acceptance as an imaging modality for oncology as it offers superior soft-tissue contrast compared with CT alone, and it has been suggested that information from PET/CT and MR is complementary in head and neck cancer.²² The introduction of the integrated PET/MR scanner offers a unique opportunity to combine the high soft-tissue contrast of MR with the functional imaging from PET within a single imaging session. PET/MR is still in its infancy, but the combined modality imaging is potentially useful in the management of patients with HNSCC.^22–28 However, the same criteria of reproducibility as with PET/CT should be upheld by this new modality. The purpose of this prospective test–retest study is to assess the reproducibility of both ¹⁸F-FDG PET/CT and ¹⁸F-FDG PET/MR in a homogenous cohort of patients with HNSCC.     

Incidental Focal 18F-FDG Uptake in the Prostate: Clinical Significance and Differential Diagnostic Criteria

Purpose

The extent and intensity of ¹⁸F-FDG uptake in prostate cancer patients are known to be variable, and the clinical significance of focal ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) uptake that is incidentally found on positron emission tomography (PET) has not been established. We investigated the clinical significance of incidental focal prostate uptake of ¹⁸F-FDG on PET/computed tomography (CT) and analyzed differential findings on PET/CT between malignant and benign uptake.

Methods

A total of 14,854 whole-body ¹⁸F-FDG PET/CT scans (4,806 that were conducted during cancer screening and 10,048 that were conducted to evaluate suspected or alleged cancer outside of the prostate) were retrospectively reviewed to determine the presence, location, multiplicity and maximum standardized uptake value (SUVmax) of focal prostate uptake and combined calcification. The final diagnosis determined by serum prostate-specific antigen (PSA) level and biopsy was compared with PET findings.

Results

Incidental focal prostate uptake was observed in 148 of 14,854 scans (1.0 %). Sixty-seven of these 148 subjects who had diagnostic confirmation were selected for further analysis. Prostate cancer was diagnosed in nine of 67 subjects (13.4%). The remaining 58 subjects had no malignancy in the prostate based on normal serum PSA level (n = 53), or elevated serum PSA level with a negative biopsy result (n = 5). While 84.6% (11/13) of malignant uptake was peripherally located in the prostate glands, 60.2% (50/83) of benign uptake was centrally located (p < 0.05). The positive predictive value of peripheral focal uptake for malignancy was 25%. The SUVmax, multiplicity and combined calcification were not significantly different between the two groups.

Conclusion

Although incidental focal ¹⁸F-FDG uptake in the prostate is not common, the incidence of cancer with focal uptake is not low. Therefore, these findings deserve further evaluation. The location of the focal prostate uptake may help with the selection of high-risk prostate cancer patients.