Quantitative classification and radiomics of [18F]FDG-PET/CT in indeterminate thyroid nodules.

PURPOSE: To evaluate whether quantitative [18F]FDG-PET/CT assessment, including radiomic analysis of [18F]FDG-positive thyroid nodules, improved the preoperative differentiation of indeterminate thyroid nodules of non-Hürthle cell and Hürthle cell cytology. METHODS: Prospectively included patients with a Bethesda III or IV thyroid nodule underwent [18F]FDG-PET/CT imaging. Receiver operating characteristic (ROC) curve analysis was performed for standardised uptake values (SUV) and SUV-ratios, including assessment of SUV cut-offs at which a malignant/borderline neoplasm was reliably ruled out (≥ 95% sensitivity). [18F]FDG-positive scans were included in radiomic analysis. After segmentation at 50% of SUVpeak, 107 radiomic features were extracted from [18F]FDG-PET and low-dose CT images. Elastic net regression classifiers were trained in a 20-times repeated random split. Dimensionality reduction was incorporated into the splits. Predictive performance of radiomics was presented as mean area under the ROC curve (AUC) across the test sets. RESULTS: Of 123 included patients, 84 (68%) index nodules were visually [18F]FDG-positive. The malignant/borderline rate was 27% (33/123). SUV-metrices showed AUCs ranging from 0.705 (95% CI, 0.601-0.810) to 0.729 (0.633-0.824), 0.708 (0.580-0.835) to 0.757 (0.650-0.864), and 0.533 (0.320-0.747) to 0.700 (0.502-0.898) in all (n = 123), non-Hürthle (n = 94), and Hürthle cell (n = 29) nodules, respectively. At SUVmax, SUVpeak, SUVmax-ratio, and SUVpeak-ratio cut-offs of 2.1 g/mL, 1.6 g/mL, 1.2, and 0.9, respectively, sensitivity of [18F]FDG-PET/CT was 95.8% (95% CI, 78.9-99.9%) in non-Hürthle cell nodules. In Hürthle cell nodules, cut-offs of 5.2 g/mL, 4.7 g/mL, 3.4, and 2.8, respectively, resulted in 100% sensitivity (95% CI, 66.4-100%). Radiomic analysis of 84 (68%) [18F]FDG-positive nodules showed a mean test set AUC of 0.445 (95% CI, 0.290-0.600) for the PET model. CONCLUSION: Quantitative [18F]FDG-PET/CT assessment ruled out malignancy in indeterminate thyroid nodules. Distinctive, higher SUV cut-offs should be applied in Hürthle cell nodules to optimize rule-out ability. Radiomic analysis did not contribute to the additional differentiation of [18F]FDG-positive nodules. TRIAL REGISTRATION NUMBER: This trial is registered with ClinicalTrials.gov: NCT02208544 (5 August 2014), https://clinicaltrials.gov/ct2/show/NCT02208544 .

Prospective Validation of Gallium-68 Prostate Specific Membrane Antigen-Positron Emission Tomography/Computerized Tomography for Primary Staging of Prostate Cancer.

PURPOSE: Prospective validation of 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography is lacking in initial staging of prostate cancer. In this study we evaluated the diagnostic accuracy of 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography for detecting lymph node metastasis in patients with intermediate-high risk prostate cancer. MATERIALS AND METHODS: Patients with newly diagnosed prostate cancer and negative bone scan findings at greater than 10% MSKCC (Memorial Sloan Kettering Cancer Center) risk for lymph node metastasis were prospectively included in study from October 2017 to October 2018. In candidates for extended pelvic lymph node dissection 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography was performed prior to planned surgery. Scan results were evaluated in a second tumor board meeting to assess a potential change of management. Sensitivity, specificity, and positive and negative predictive value for detecting lymph node metastasis were calculated per patient and per resection template using histopathology as the reference. A positron emission tomography based change of management was also reported. RESULTS: A total of 103 patients were eligible for analysis and 97 extended pelvic lymph node dissections were performed. In 41 patients (42.3%) there was a total of 85 lymph node metastases. Positron emission tomography was positive in 17 patients, resulting in 41.5% patient based sensitivity (95% CI 26.7-57.8) for detecting lymph node metastasis. The patient based specificity rate was 90.9% (95% CI 79.3-96.6), and positive and negative predictive values were 77.3% (95% CI 54.2-91.3) and 67.6% (95% CI 55.6-77.7), respectively. A positron emission tomography based change of treatment was observed in 13 patients (12.6%). CONCLUSIONS: In patients with newly diagnosed prostate cancer at greater than 10% MSKCC risk for lymph node involvement 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography detected lymph node metastasis with high specificity and moderate sensitivity. This led to a treatment change in 12.6% of patients.

A randomised, phase II study of repeated rhenium-188-HEDP combined with docetaxel and prednisone versus docetaxel and prednisone alone in castration-resistant prostate cancer (CRPC) metastatic to bone; the Taxium II trial.

BACKGROUND: Rhenium-188-HEDP is a beta-emitting radiopharmaceutical used for palliation of metastatic bone pain. We investigated whether the addition of rhenium-188-HEDP to docetaxel/prednisone improved efficacy of chemotherapy in patients with CRPC. METHODS: Patients with progressive CRPC and osteoblastic bone metastases were randomised for first-line docetaxel 75 mg/m2 3-weekly plus prednisone with or without 2 injections of rhenium-188-HEDP after the third (40 MBq/kg) and after the sixth (20 MBq/kg) cycle of docetaxel. Primary endpoint was progression-free survival (PFS), defined as either PSA, radiographic or clinical progression. Patients were stratified by extent of bone metastases and hospital. RESULTS: Forty-two patients were randomised for standard treatment and 46 patients for combination therapy. Median number of cycles of docetaxel was 9 in the control group and 8 in the experimental group. Median follow-up was 18.4 months. Two patients from the experimental group did not start treatment after randomisation. In the intention to treat analysis no differences in PFS, survival and PSA became apparent between the two groups. In an exploratory per-protocol analysis median overall survival was significantly longer in the experimental group (33.8 months (95%CI 31.75-35.85)) than in the control group (21.0 months (95%CI 13.61-28.39); p 0.012). Also median PFS in patients with a baseline phosphatase >220U/L was significantly better with combination treatment (9.0 months (95%CI 3.92-14.08) versus 6.2 months (95%CI 3.08-9.32); log rank p 0.005). As expected, thrombocytopenia (grade I/II) was reported more frequently in the experimental group (25% versus 0%). CONCLUSION: Combined treatment with rhenium-188-HEDP and docetaxel did not prolong PFS in patients with CRPC. The observed survival benefit in the per-protocol analysis warrants further studies in the combined treatment of chemotherapy and radiopharmaceuticals.

Malignancy rate of biopsied suspicious bone lesions identified on FDG PET/CT.

PURPOSE: To determine the malignancy rate of bone lesions identified on FDG PET/CT in patients who have undergone CT-guided biopsy because of the suspicion of malignancy. METHODS: This single-centre retrospective study spanned eight consecutive years and included all patients who underwent both FDG PET/CT and CT-guided bone biopsy because of the suspicion of malignancy. The positive predictive value (PPV) for malignancy was calculated, and different patient and imaging characteristics were compared between malignant and benign bone lesions. RESULTS: Of 102 included patients with bone lesions that all showed FDG uptake exceeding mediastinal uptake, bone biopsy showed a malignant lesion in 91 patients, yielding a PPV for malignancy of 89.2 % (95 % CI 81.7 - 93.9 %). In the 94 patients with bone lesions that showed FDG uptake exceeding liver uptake, bone biopsy showed a malignant lesion in 83 patients, yielding a PPV for malignancy of 88.3 % (95 % CI 80.1 - 93.5 %). Higher age, bone marrow replacement of the lesion seen on CT, expansion of the lesion seen on CT, and presence of multifocal lesions on FDG PET/CT were significantly more frequent in patients with malignant lesions than in those with benign bone lesions (P = 0.044, P = 0.009, P = 0.015, and P = 0.019, respectively). Furthermore, there was a trend towards a higher incidence of cortical destruction (P = 0.056) and surrounding soft tissue mass (P = 0.063) in patients with malignant bone lesions. CONCLUSION: The PPV for malignancy of suspicious bone lesions identified on FDG PET/CT is not sufficiently high to justify changes in patient management without histopathological confirmation. Nevertheless, ancillary patient and imaging characteristics may increase the likelihood of a malignant bone lesion.

Where Does Diffuse Large B-Cell Lymphoma Relapse?

OBJECTIVE: This study aimed to investigate the anatomic pattern of disease spread at first disease relapse compared with baseline in diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS: All patients who were newly diagnosed as having DLBCL between January 2004 and June 2014 who initially achieved complete remission but who eventually developed relapsed disease during follow-up were retrospectively identified. Available histological and imaging data were used to determine which nodal regions and extranodal locations were involved at relapse. RESULTS: A total of 21 patients with relapsed DLBCL were included, of whom 8 (38.1%) presented with disease relapse at previously involved sites only, 7 (33.3%) presented with disease relapse at both previously involved and new sites, and 6 (28.6%) presented with disease relapse at new sites only. A total of 57 nodal stations and 34 extranodal locations were involved in all 21 relapsed DLBCL patients. Of these 57 involved nodal regions, 47 (82.5%) were also involved at baseline, whereas 10 (17.5%) were not involved at baseline. Of the 34 involved extranodal locations, 17 (50.0%) were also involved at baseline, whereas 17 (50.0%) were not involved at baseline. CONCLUSIONS: Relapsed DLBCL generally tends to affect previously involved sites, although close to one third of patients seem to have disease recurrence exclusively in previously uninvolved sites. The great majority of involved nodal stations at relapse are also involved at baseline, whereas only one half of involved extranodal locations at relapse are involved at baseline.

Computed Tomography Observer Agreement in Staging Malignant Lymphoma.

OBJECTIVE: To determine pretreatment computed tomography observer agreement in patients with newly diagnosed lymphoma. METHODS: Forty-nine computed tomography scans were reviewed by 3 experienced radiologists, with each scan assessed twice by 1 observer. Predefined nodal and extranodal regions were assessed, and Ann Arbor stages were assigned. K-statistics were defined as poor (κ < 0.2), fair (κ > 0.2 to κ ≤ 0.4), moderate (κ > 0.4 to κ ≤ 0.6), substantial (κ > 0.6 to κ ≤ 0.8), and almost perfect (κ > 0.8 to κ ≤ 1). RESULTS: Nodal interobserver agreement varied from 0.09 for infraclavicular involvement to 0.95 for para-iliac involvement; intraobserver agreement was substantial to almost perfect, except for infraclavicular nodes. Extranodal interobserver agreement varied from 0.56 to 0.88; intraobserver agreement was substantial to almost perfect. Ann Arbor stage interobserver agreement varied from 0.57 to 0.69; intraobserver agreement was substantial. CONCLUSION: Computed tomography observer agreement in staging malignant lymphoma appears to be suboptimal.

CT-based versus FDG-PET/CT-based NCCN international prognostic index risk stratification in DLBCL.

BACKGROUND: This study compared CT-based and (18)F-fluoro-2-deoxy-D-glucose PET/CT (FDG-PET/CT)-based NCCN International Prognostic Index (NCCN-IPI) risk stratification in newly diagnosed diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS: This retrospective study included 57 patients with newly diagnosed DLBCL who had undergone both (oral and intravenous contrast-enhanced full-dose) diagnostic CT and FDG-PET/CT. Diagnostic CT only and FDG-PET/CT were evaluated separately, and corresponding NCCN-IPI scores for the 2 datasets (NCCN-IPICT and NCCN-IPIPET/CT) were calculated. Percentages of agreement and weighted k statistic between NCCN-IPICT and NCCN-IPIPET/CT scoring with regard to the formation of low-, low-intermediate-, high-intermediate-, and high-risk groups were calculated. RESULTS: In 47 of 57 patients (82.5%; 95% CI, 70.4-90.4), diagnostic CT alone was in agreement with FDG-PET/CT with regard to the formation of low-, low-intermediate-, high-intermediate-, and high-risk NCCN-IPI groups, but not in the remaining 10 patients (17.5%; 95% CI, 9.6%-29.6%). All NCCN-IPI disagreements between diagnostic CT and FDG-PET/CT were from the detection of additional lesions by the latter, most of them being bone marrow lesions. Agreement between NCCN-IPICT and NCCN-IPIPET/CT with regard to the formation of low-, low-intermediate-, high-intermediate-, and high-risk groups was considered good (k=0.771). CONCLUSIONS: Although agreement between NCCN-IPICT and NCCN-IPIPET/CT risk stratification is generally good, FDG-PET/CT results in higher NCCN-IPI risk stratifications in a non-negligible proportion of patients. Future studies should investigate the prognostic implications of these imaging-based differences in NCCN-IPI scoring.

Prognostic superiority of the National Comprehensive Cancer Network International Prognostic Index over pretreatment whole-body volumetric-metabolic FDG-PET/CT metrics in diffuse large B-cell lymphoma.

PURPOSE: This study aimed to determine the prognostic value of whole-body maximum standardized uptake value (SUVmax ), whole-body metabolic tumor volume (MTV), and whole-body total lesion glycolysis (TLG) at pretreatment (18) F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS: Seventy-three patients with newly diagnosed DLBCL who had undergone FDG-PET/CT before rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisolone (R-CHOP) immunochemotherapy were retrospectively included. All FDG-avid lesions in each patient were segmented using semi-automated software to calculate whole-body SUVmax , whole-body MTV, and whole-body TLG values. Cox regression analyses were used to determine the associations of whole-body SUVmax , whole-body MTV, whole-body TLG, and dichotomized National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) risk group (low risk vs. high risk) with progression-free survival (PFS) and overall survival (OS). RESULTS: On univariate Cox regression analysis, only the NCCN-IPI was a significant predictor of PFS (P = 0.024), and only the NCCN-IPI and whole-body MTV were significant predictors of OS (P = 0.039 and P = 0.043, respectively). In the multivariate Cox proportional hazards model, only the NCCN-IPI remained an independent predictive factor of PFS (P = 0.024) and OS (P = 0.039). CONCLUSION: Whole-body SUVmax , whole-body MTV, and whole-body TLG do not provide any prognostic information in DLBCL beyond that which can already be obtained by the NCCN-IPI. Therefore, the NCCN-IPI remains the most important prognostic tool in this disease.

Diffusely increased bone marrow FDG uptake in recently untreated lymphoma: incidence and relevance.

PURPOSE: To determine the incidence of diffusely increased bone marrow (18) F-fluoro-2-deoxy-D-glucose (FDG) uptake at positron emission tomography (PET) in recently untreated lymphoma and to assess the frequency of lymphoma-positive bone marrow biopsies (BMBs) in these patients. METHODS: FDG-PET scans of all patients presenting with newly diagnosed or relapsed lymphoma were reviewed. Patients with non-focal diffusely increased bone marrow FDG uptake, who had not received therapy within 3 months, were identified. The incidences of diffusely increased bone marrow FDG uptake and the frequencies of positive posterior iliac crest BMBs among those cases were calculated. RESULTS: The incidences of diffusely increased bone marrow FDG uptake in all lymphomas, and in Hodgkin lymphoma, aggressive non-Hodgkin lymphoma (NHL), indolent NHL, and mantle cell NHL separately, were 4.2% (23/542), 9.3% (7/75), 3.4% (8/239), 3.3% (7/214), and 7.1% (1/14), respectively, and frequencies of positive BMBs among these subgroups were 55.0% (11/20), 0.0% (0/7), 83.3% (5/6), 83.3% (5/6), and 100% (1/1), respectively. CONCLUSION: The incidence of diffusely increased bone marrow FDG uptake in recently untreated lymphoma is low, albeit higher in Hodgkin lymphoma than in NHL. BMB in such patients is likely to be negative in Hodgkin lymphoma, but positive in the majority of NHL cases.

Bone marrow biopsy in diffuse large B-cell lymphoma: useful or redundant test?

PURPOSE: To determine the additional value of bone marrow biopsy (BMB) in the standard staging work-up of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), in terms of risk assessment and treatment planning. MATERIAL AND METHODS: A total of 113 consecutive patients with newly diagnosed DLBCL who had undergone standard pretreatment evaluation, including serum lactate dehydrogenase measurement, Eastern Cooperative Oncology Group performance status assessment, computed tomography or (18)F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography, and BMB, were retrospectively included. National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) score and treatment strategy were determined in each patient, once without and once with taking into account BMB results. Numbers and percentages of BMB-induced changes on NCCN-IPI-based risk stratification (i.e. formation of low, low-intermediate, high-intermediate, and high risk groups) and choice of treatment were calculated, along with 95% confidence intervals (CIs). RESULTS: BMB was positive in 18 of 113 patients (15.9%, 95% CI 10.2-23.9 %). BMB-induced changes on NCCI-IPI-based risk stratification occurred in 9 of 113 patients (8.0%, 95% CI 4.1-14.6%). Five patients were upstaged from low-intermediate to high-intermediate risk, and four patients were upstaged from high-intermediate to high risk. BMB findings changed treatment planning in none of the 113 patients (0.0%, 95% CI 0.0-4.0%). CONCLUSION: Although BMB results upstaged the NCCN-IPI-based risk stratification in a small number of cases, this did not have any therapeutic implications in our patient series. These findings support the omission of BMB from routine staging of newly diagnosed DLBCL in the current risk stratification and treatment era.

Residual Anatomical Disease in Diffuse Large B-Cell Lymphoma Patients With FDG-PET-Based Complete Response After First-Line R-CHOP Therapy: Does It Have Any Prognostic Value?

OBJECTIVE: This study aimed to determine the prognostic value of residual anatomical disease, including its size and reduction relative to baseline, in diffuse large B-cell lymphoma patients who have F-fluoro-2-deoxy-d-glucose positron emission tomography-based complete response after first-line R-CHOP therapy. METHODS: This retrospective study included 47 patients. In patients with computed tomography (CT)-based residual disease, the size of the largest residual lesion (Resmax) and the sum of the sizes of all residual lesions (Restotal) were measured, and their reductions relative to baseline (ΔResmax and ΔRestotal) were calculated. RESULTS: Patients with high-risk National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) scores had significantly lower progression-free survival (PFS) and overall survival (OS) than patients with low-risk NCCN-IPI scores (P = 0.032 and P = 0.022). In contrast, patients with residual lesions at CT had no significantly lower PFS and OS than those without (P = 0.531 and P = 0.801). In the subpopulation with CT-based residual disease, patients with high Resmax, high Restotal, low ΔResmax, and low ΔRestotal had no significantly different PFS and OS than those with low Resmax, low Restotal, high ΔResmax, and high ΔRestotal (P = 0.980 and P = 0.790, P = 0.423 and P = 0.229, P = 0.923 and P = 0.893, and P = 0.923 and P = 0.893, respectively). CONCLUSIONS: The NCCN-IPI retains its prognostic value in diffuse large B-cell lymphoma patients with F-fluoro-2-deoxy-d-glucose positron emission tomography-based complete response after first-line R-CHOP therapy. However, the presence of residual anatomical disease, including its size and reduction relative to baseline, has no prognostic value in these patients.

Direct comparison of visual and quantitative bone marrow FDG-PET/CT findings with bone marrow biopsy results in diffuse large B-cell lymphoma: does bone marrow FDG-PET/CT live up to its promise?

BACKGROUND: Detection of bone marrow involvement using 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) has been proposed as a non-invasive alternative to standard blind bone marrow biopsy (BMB) of the posterior iliac crest in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). However, studies that directly compare FDG-PET/CT results with histopathology are currently lacking. PURPOSE: To directly compare both visual and quantitative bone marrow FDG-PET/CT to BMB at the right posterior iliac crest in patients with newly diagnosed DLBCL. MATERIAL AND METHODS: A total of 40 patients with newly diagnosed DLBCL, who had undergone FDG-PET/CT before BMB of the right posterior iliac crest, were retrospectively included. FDG-PET/CT images were visually assessed for bone marrow involvement in the right posterior iliac crest. 3D partial volume corrected mean standardized uptake value (cSUVmean), maximum standardized uptake value (SUVmax), and peak standardized uptake value (SUVpeak) were measured in the right posterior iliac crest, using volume of interest analysis. BMB of the right posterior iliac crest was used as reference standard for bone marrow involvement. RESULTS: Sensitivity and specificity of visual FDG-PET/CT analysis for the detection of bone marrow involvement in the right posterior iliac crest were 14.3% (95% confidence interval [CI], 0.5-53.4%) and 100% (95% CI, 87.6-100%), respectively. cSUVmean, SUVmax, and SUVpeak of BMB-negative patients (1.4 ± 0.49, 2.2 ± 0.69, and 1.7 ± 0.59, respectively) considerably overlapped with those of BMB-positive patients (1.8 ± 0.53, 2.7 ± 0.71, and 2.2 ± 0.61, respectively). CONCLUSION: In a local, head-to-head comparison with BMB, the diagnostic value of both visual and quantitative FDG-PET/CT for the detection of bone marrow involvement is low in patients with newly diagnosed DLBCL.

Does the presence of tumor-induced cortical bone destruction at CT have any prognostic value in newly diagnosed diffuse large B-cell lymphoma?

PURPOSE: To determine the prognostic value of tumor-induced cortical bone destruction at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS: This retrospective study included 105 patients with newly diagnosed DLBCL who had undergone CT and bone marrow biopsy (BMB) before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone) chemo-immunotherapy. Cox regression analyses were used to determine the associations of cortical bone status at CT (absence vs. presence of tumor-induced cortical bone destruction), BMB findings (negative vs. positive for lymphomatous involvement), and dichotomized National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) strata (low risk vs. high risk) with progression-free survival (PFS) and overall survival (OS). RESULTS: Univariate Cox regression analysis indicated that cortical bone status at CT was no significant predictor of either PFS or OS (p = 0.358 and p = 0.560, respectively), whereas BMB findings (p = 0.002 and p = 0.013, respectively) and dichotomized NCCN-IPI risk strata (p = 0.002 and p = 0.003, respectively) were significant predictors of both PFS and OS. In the multivariate Cox proportional hazards model, only the dichotomized NCCN-IPI score was an independent predictive factor of PFS and OS (p = 0.004 and p = 0.003, respectively). CONCLUSIONS: The presence of tumor-induced cortical bone destruction at CT was not found to have any prognostic implications in newly diagnosed DLBCL.

FDG PET/CT for the detection of bone marrow involvement in diffuse large B-cell lymphoma: systematic review and meta-analysis.

PURPOSE: To systematically review and meta-analyse published data on the diagnostic performance of (18)F-FDG PET/CT in detecting bone marrow involvement in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). METHODS: PubMed/MEDLINE and Embase were systematically searched for relevant studies. The methodological quality of each study was assessed. Sensitivities and specificities of FDG PET/CT in individual studies were calculated and meta-analysed with a random effects model. A summary receiver operating characteristic curve (sROC) was constructed with the Moses-Shapiro-Littenberg method. Weighted summary proportions of discrepancies between the FDG PET/CT and (blind) bone marrow biopsy (BMB) results among all patients were calculated. RESULTS: Seven studies, with a total of 654 patients with newly diagnosed DLBCL, were included. Overall, the quality of the included studies was moderate. The sensitivity and specificity of FDG PET/CT for detecting bone marrow involvement ranged from 70.8% to 95.8% and from 99.0% to 100%, with pooled estimates of 88.7% (95% confidence interval, CI, 82.5-93.3%) and 99.8% (95% CI 98.8-100%), respectively. The area under the sROC curve was 0.9983. The weighted summary proportion of FDG PET/CT-negative patients with positive BMB findings among all patients was 3.1% (95% CI 1.8-5.0%) and the weighted summary proportion of FDG PET/CT-positive patients with negative BMB findings among all patients was 12.5% (95% CI 8.4-17.3%). CONCLUSION: FDG PET/CT is accurate and complementary to BMB for detecting bone marrow involvement in patients with newly diagnosed DLBCL. A negative FDG PET/CT scan cannot rule out the presence of bone marrow involvement, but positive FDG PET/CT findings obviate the need for BMB for the detection of bone marrow involvement in these patients.

Whole-body MRI, including diffusion-weighted imaging, for staging lymphoma: comparison with CT in a prospective multicenter study.

PURPOSE: To compare whole-body magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI), to computed tomography (CT) for staging newly diagnosed lymphoma. MATERIALS AND METHODS: In all, 108 patients with newly diagnosed lymphoma prospectively underwent whole-body MRI (T1-weighted and T2-weighted short inversion time inversion recovery [n = 108], and DWI [n = 104]) and CT. Ann Arbor stages were assigned according to whole-body MRI and CT findings. Staging disagreements were resolved using bone marrow biopsy, FDG-PET, and follow-up studies. The results were descriptively analyzed. RESULTS: Staging results of whole-body MRI without DWI were equal to those of CT in 66.6%, higher in 24.1%, and lower in 9.3%, with correct/incorrect/unresolved higher staging and incorrect/unresolved lower staging relative to CT in 15/7/4 and 9/1 patient(s), respectively. Staging results of whole-body MRI with DWI were equal to those of CT in 65.4%, higher in 27.9%, and lower in 6.7%, with correct/incorrect/unresolved higher staging and incorrect/unresolved lower staging relative to CT in 18/6/5 and 6/1 patient(s), respectively. CONCLUSION: The results of this study suggest that whole-body MRI staging equals CT staging in the majority of patients with newly diagnosed lymphoma. No advantage of additional DWI was demonstrated. Whole-body MRI can be a good alternative to CT if radiation exposure should be avoided.

Bone marrow 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography cannot replace bone marrow biopsy in diffuse large B-cell lymphoma.

This study aimed to investigate whether visual and quantitative (18) F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT)-based bone marrow assessment can replace blind bone marrow biopsy (BMB) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). This retrospective study included 78 patients with newly diagnosed DLBCL who had undergone both FDG-PET/CT and BMB. FDG-PET/CT images were visually evaluated for bone marrow involvement. Patient-based sensitivity of visual FDG-PET/CT assessment was calculated using BMB as the reference standard. Metabolically active volume, maximum standardized uptake value, 3D partial volume corrected mean standardized uptake value, and 3D partial volume corrected mean metabolic volume product (cMVPmean ) of FDG-avid bone marrow lesions were measured. Cox regression analysis was used to determine the influence of (potential) prognostic factors (BMB status, visual [dichotomous] FDG-PET/CT bone marrow status, metabolically active volume, maximum standardized uptake value, 3D partial volume corrected mean standardized uptake value, 3D partial volume corrected mean metabolic volume product, and International Prognostic Index score) on progression-free survival and overall survival. FDG-PET/CT detected bone marrow involvement in 34 (43.6%) cases and BMB in 16 (20.5%) of 78 cases, of whom 11 were also detected by FDG-PET/CT, resulting in a patient-based sensitivity of 68.8% (95% confidence interval = 44.2%-86.1%) for FDG-PET/CT. In the multivariate Cox proportional hazards model, only BMB status was an independent predictive factor of progression-free survival (P = 0.016) and overall survival (P = 0.004). In conclusion, FDG-PET/CT misses bone marrow involvement that has been detected by BMB in a non-negligible proportion of patients. Furthermore, both visual and quantitative FDG-PET/CT-based bone marrow assessments are prognostically inferior to BMB. Therefore, FDG-PET/CT cannot replace BMB in newly diagnosed DLBCL.

Can full-dose contrast-enhanced CT be omitted from an FDG-PET/CT staging examination in newly diagnosed FDG-avid lymphoma?

OBJECTIVE: To determine whether full-dose contrast-enhanced computed tomography (CT) (CECT) can be omitted from an F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) (FDG-PET)/CT staging examination in newly diagnosed FDG-avid lymphoma. METHODS: Twenty-nine patients with newly diagnosed FDG-avid lymphoma prospectively underwent unenhanced low-dose FDG-PET/CT and CECT. Different observers evaluated unenhanced low-dose FDG-PET/CT and CECT in a blinded manner. Ann Arbor stages according to unenhanced low-dose FDG-PET/CT and CECT were compared, and discrepancies between the 2 imaging modalities were resolved using bone marrow biopsy and posttreatment FDG-PET/CT as reference standard. Finally, it was assessed as to how many cases therapy would have been changed based on additional CECT findings. RESULTS: In 27 of 29 patients (93%; 95% confidence interval, 78%-98%), CECT either did not change or did not correctly change the Ann Arbor stage that was assigned according to unenhanced low-dose FDG-PET findings. In 2 of 29 patients (7%; 95% confidence interval, 2%-22%), CECT correctly provided another Ann Arbor stage than unenhanced low-dose FDG-PET/CT. In the latter 2 cases, therapy would not have been changed based on additional CECT findings. CONCLUSIONS: Unenhanced low-dose FDG-PET/CT alone is suggested as the primary imaging modality of choice for staging patients with newly diagnosed FDG-avid lymphoma. This diagnostic approach is particularly indicated in younger patients in whom diagnostic radiation exposure should be minimized and in patients who are at increased risk of CT contrast-induced allergic reactions or nephropathy.

Utility of quantitative FDG-PET/CT for the detection of bone marrow involvement in follicular lymphoma: a histopathological correlation study.

OBJECTIVE: To determine the value of visual and quantitative (18) F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) for the detection of bone marrow involvement in follicular lymphoma, using direct histopathological examination at the right posterior iliac crest as reference standard. MATERIALS AND METHODS: This retrospective study included 22 patients with newly diagnosed follicular lymphoma who had undergone FDG-PET/CT before BMB of the right posterior iliac crest. FDG-PET/CT images were visually evaluated for bone marrow involvement in the right posterior iliac crest. Volumes of interest were placed in the right posterior iliac crest to calculate the 3D partial volume corrected mean standardized uptake value (cSUVmean), maximum standardized uptake value (SUVmax) and peak standardized uptake value (SUVpeak). RESULTS: Sensitivity and specificity of visual FDG-PET/CT analysis for the detection of bone marrow involvement in the right posterior iliac crest were 0.0 % (95 % confidence interval (CI): 0-32.4 %) and 100 % (95 % CI: 78.5-100 %), respectively. Areas under the receiver-operating characteristic curve of cSUVmean, SUVmax and SUVpeak for the detection of bone marrow involvement in the right posterior iliac crest were 0.85 (95 % CI: 0.63-0.96), 0.89 (95 % CI: 0.68-0.98) and 0.87 (95 % CI: 0.65-0.97), respectively. Optimal cutoff values for cSUVmean, SUVmax and SUVpeak were 1.3, 2.1 and 1.7, and yielded sensitivity and specificity combinations of 75.0 % and 85.7 %, 87.5 % and 85.7 % and 87.5 % and 85.7 %, respectively. CONCLUSION: This histopathological correlation study shows that, unlike visual interpretation of FDG-PET/CT images, quantitative FDG-PET/CT analysis may be beneficial in diagnosing bone marrow involvement by follicular lymphoma.

Whole-body MRI for the detection of bone marrow involvement in lymphoma: prospective study in 116 patients and comparison with FDG-PET.

OBJECTIVE: To assess and compare the value of whole-body MRI with FDG-PET for detecting bone marrow involvement in lymphoma. METHODS: A total of 116 patients with newly diagnosed lymphoma prospectively underwent whole-body MRI and blind bone marrow biopsy (BMB) of the posterior iliac crest. Of 116 patients, 80 also underwent FDG-PET. Patient-based sensitivities of whole-body MRI for detecting bone marrow involvement were calculated using BMB as reference standard and compared with FDG-PET in aggressive and indolent lymphomas separately. RESULTS: Sensitivity of whole-body MRI in all lymphomas was 45.5 % [95 % confidence interval (CI): 29.8-62.0 %]. Sensitivity of whole-body MRI in aggressive lymphoma [88.9 % (95 % CI: 54.3-100 %)] was significantly higher (P = 0.0029) than that in indolent lymphoma [23.5 % (95 % CI: 9.1-47.8 %)]. Sensitivity of FDG-PET in aggressive lymphoma [83.3 % (95 % CI: 41.8-98.9 %)] was also significantly higher (P = 0.026) than that in indolent lymphoma [12.5 % (95 % CI: 0-49.2 %)]. There were no significant differences in sensitivity between whole-body MRI and FDG-PET (P = 1.00) CONCLUSION: Sensitivity of whole-body MRI for detecting lymphomatous bone marrow involvement is too low to (partially) replace BMB. Sensitivity of whole-body MRI is significantly higher in aggressive lymphoma than in indolent lymphoma and is equal to FDG-PET in both entities. KEY POINTS: • Bone marrow involvement in lymphoma has prognostic and therapeutic implications. • Blind bone marrow biopsy (BMB) is standard for bone marrow assessment. • Neither whole-body MRI nor FDG-PET can yet replace BMB. • Both techniques have higher sensitivity in aggressive than in indolent lymphoma. • Both imaging techniques are complementary to BMB.