Additional Value of FDG-PET/MRI Complementary to Sentinel Lymphonodectomy for Minimal Invasive Lymph Node Staging in Patients with Endometrial Cancer: A Prospective Study.

BACKGROUND: Lymph node metastases (LNM) are rare in early-stage endometrial cancer, but a diagnostic systematic lymphadenectomy (LNE) is often performed to achieve reliable N-staging. Therefore, this prospective study aimed to evaluate the benefit of [18F]-Fluorodeoxyglucose (FDG) PET/MRI complementary to SPECT/CT guided sentinel lymphonodectomy (SLNE) for a less invasive N-staging Methods: 79 patients underwent a whole-body FDG-PET/MRI, SLN mapping with 99mTc-Nanocolloid SPECT/CT and indocyanine green (ICG) fluoroscopy followed by LNE which served as ground truth. RESULTS: FDG-PET/MRI was highly specific in N-staging (97.2%) but revealed limited sensitivity (66.7%) due to missed micrometastases. In contrast, bilateral SLN mapping failed more often in patients with macrometastases. The combination of SLN mapping and FDG-PET/MRI increased the sensitivity from 66.7% to 77.8%. Additional SLN labeling with dye (ICG) revealed a complete SLN mapping in 80% (8/10) of patients with failed or incomplete SLN detection in SPECT/CT, reducing the need for diagnostic systematic LNE up to 87%. FDG-PET/MRI detected para-aortic LNM in three out of four cases and a liver metastasis. CONCLUSIONS: The combination of FDG-PET/MRI and SLNE can reduce the need for diagnostic systematic LNE by up to 87%. PET/MRI complements the SLN technique particularly in the detection of para-aortic LNM and occasional distant metastases.

Non-invasive estimation of split renal function from routine 68Ga-SSR-PET/CT scans.

Objective: Patients with impaired kidney function are at elevated risk for nephrotoxicity and hematotoxicity from peptide receptor radionuclide therapy (PPRT) for advanced neuroendocrine tumors. Somatostatin receptor (SSR)-PET/CT imaging is the method of choice to identify sufficient SSR expression as a prerequisite for PRRT. Therefore, our study aimed to explore whether split renal function could be evaluated using imaging data from routine SSR-PET/CT prior to PRRT. Methods: In total, 25 consecutive patients who underwent SSR-PET/CT (Siemens Biograph mCT®) before PRRT between June 2019 and December 2020 were enrolled in this retrospective study. PET acquisition in the caudocranial direction started at 20 ± 0.5 min after an i.v. injection of 173 ± 20 MBq [68Ga]Ga-ha DOTATATE, and the kidneys were scanned at 32 ± 0.5 min p.i. The renal parenchyma was segmented semi-automatically using an SUV-based isocontour (SUV between 5 and 15). Multiple parameters including SUVmean of renal parenchyma and blood pool, as well as parenchyma volume, were extracted, and accumulation index (ACI: renal parenchyma volume/SUVmean) and total kidney accumulation (TKA: SUVmean x renal parenchyma volume) were calculated. All data were correlated with the reference standard tubular extraction rate (TER-MAG) from [99mTc]Tc-MAG3 scintigraphy and glomerular filtration rate (GFRCDK - EPI). Results: SUVmean of the parenchymal tracer retention showed a negative correlation with TERMAG (r: -0.519, p < 0.001) and GFRCDK - EPI (r: -0.555, p < 0.001) at 32 min p.i. The herein-introduced ACI revealed a significant correlation (p < 0.05) with the total tubular function (r: 0.482), glomerular renal function (r: 0.461), split renal function (r: 0.916), and absolute single-sided renal function (r: 0.549). The mean difference between the split renal function determined by renal scintigraphy and ACI was 1.8 ± 4.2 % points. Conclusion: This pilot study indicates that static [68Ga]Ga-ha DOTATATE PET-scans at 32 min p.i. may be used to estimate both split renal function and absolute renal function using the herein proposed "Accumulation Index" (ACI).

Dual-Time-Point Posttherapy 177Lu-PSMA-617 SPECT/CT Describes the Uptake Kinetics of mCRPC Lesions and Prognosticates Patients' Outcome.

177Lu-PSMA-617 is an effective therapeutic option in metastasized castration-resistant prostate cancer (mCRPC). However, some patients progress under treatment. We hypothesized that the tracer kinetics within the metastases may influence the therapy effectiveness and tested this hypothesis by analyzing uptake parameters on 2 consecutive posttherapy SPECT/CT scans. Methods: mCRPC patients treated with 177Lu-PSMA-617 and with available posttherapy SPECT/CT imaging (24 and 48 h after the first treatment) were enrolled retrospectively. Volumes of interest were defined on lymph node metastasis (LNM) and bone metastasis (BM) on both SPECT/CT scans. The reduction of the percentage injected dose (%IDred) between the 2 SPECT/CT scans was computed. We compared %IDred of responders (prostate-specific antigen drop ≥ 50% after 2 cycles of 177Lu-PSMA-617) and nonresponders. We tested the association of %IDred with progression-free survival and overall survival (OS) using a univariate Kaplan-Meier (KM) analysis and a multivariate Cox regression model. Results: Fifty-five patients (median age, 73 y; range, 54-87 y) were included. %IDred in LNM and BM was greater in nonresponders than in responders (for LNM, 36% in nonresponders [interquartile range (IQR), 26%-47%] vs. 24% in responders [IQR, 12%-33%] [P = 0.003]; for BM, 35% in nonresponders [IQR, 27%-52%] vs. 18% in responders [IQR, 15%-29%] [P = 0.002]). For progression-free survival, in KM analysis, greater %IDred in LNM (P = 0.008) and BM (P = 0.001) was associated with shorter survival, whereas in multivariate analysis, only %IDred in LNM was retained (P = 0.03). In univariate KM analysis of OS, greater %IDred in BM was associated with shorter survival (P = 0.002). In multivariate OS analysis, BM %IDred (P = 0.009) was retained. Conclusion: The 177Lu-PSMA-617 clearance rate from mCRPC metastases appears to be a relevant prognosticator of response and survival, with faster clearing possibly signaling a shorter radiopharmaceutical residence time and absorbed dose. Dual-time-point analysis appears to be a feasible and readily available approach to estimate the likelihood of response and patients' survival.

Whole-Body Magnetic Resonance Imaging (MRI) for Staging Melanoma Patients in Direct Comparison to Computed Tomography (CT): Results from a Prospective Positron Emission Tomography (PET)/CT and PET/MRI Study.

PURPOSE: The consideration of radiation exposure is becoming more important in metastatic melanoma due to improved prognoses. The aim of this prospective study was to investigate the diagnostic performance of whole-body (WB) magnetic resonance imaging (MRI) in comparison to computed tomography (CT) with 18F-FDG positron emission tomography (PET)/CT and 18F-PET/MRI together with a follow-up as the reference standard. METHODS: Between April 2014 and April 2018, a total of 57 patients (25 females, mean age of 64 ± 12 years) underwent WB-PET/CT and WB-PET/MRI on the same day. The CT and MRI scans were independently evaluated by two radiologists who were blinded to the patients' information. The reference standard was evaluated by two nuclear medicine specialists. The findings were categorized into different regions: lymph nodes/soft tissue (I), lungs (II), abdomen/pelvis (III), and bone (IV). A comparative analysis was conducted for all the documented findings. Inter-reader reliability was assessed using Bland-Altman procedures, and McNemar's test was utilized to determine the differences between the readers and the methods. RESULTS: Out of the 57 patients, 50 were diagnosed with metastases in two or more regions, with the majority being found in region I. The accuracies of CT and MRI did not show significant differences, except in region II where CT detected more metastases compared to MRI (0.90 vs. 0.68, p = 0.008). On the other hand, MRI had a higher detection rate in region IV compared to CT (0.89 vs. 0.61, p > 0.05). The level of agreement between the readers varied depending on the number of metastases and the specific region, with the highest agreement observed in region III and the lowest observed in region I. CONCLUSIONS: In patients with advanced melanoma, WB-MRI has the potential to serve as an alternative to CT with comparable diagnostic accuracy and confidence across most regions. The observed limited sensitivity for the detection of pulmonary lesions might be improved through dedicated lung imaging sequences.

Diagnostic Performance of Dynamic Whole-Body Patlak [18F]FDG-PET/CT in Patients with Indeterminate Lung Lesions and Lymph Nodes.

BACKGROUND: Static [18F]FDG-PET/CT is the imaging method of choice for the evaluation of indeterminate lung lesions and NSCLC staging; however, histological confirmation of PET-positive lesions is needed in most cases due to its limited specificity. Therefore, we aimed to evaluate the diagnostic performance of additional dynamic whole-body PET. METHODS: A total of 34 consecutive patients with indeterminate pulmonary lesions were enrolled in this prospective trial. All patients underwent static (60 min p.i.) and dynamic (0-60 min p.i.) whole-body [18F]FDG-PET/CT (300 MBq) using the multi-bed-multi-timepoint technique (Siemens mCT FlowMotion). Histology and follow-up served as ground truth. Kinetic modeling factors were calculated using a two-compartment linear Patlak model (FDG influx rate constant = Ki, metabolic rate = MR-FDG, distribution volume = DV-FDG) and compared to SUV using ROC analysis. RESULTS: MR-FDGmean provided the best discriminatory power between benign and malignant lung lesions with an AUC of 0.887. The AUC of DV-FDGmean (0.818) and SUVmean (0.827) was non-significantly lower. For LNM, the AUCs for MR-FDGmean (0.987) and SUVmean (0.993) were comparable. Moreover, the DV-FDGmean in liver metastases was three times higher than in bone or lung metastases. CONCLUSIONS: Metabolic rate quantification was shown to be a reliable method to detect malignant lung tumors, LNM, and distant metastases at least as accurately as the established SUV or dual-time-point PET scans.

Multiparametric Dual-Time-Point [18F]FDG PET/MRI for Lymph Node Staging in Patients with Untreated FIGO I/II Cervical Carcinoma.

[18F]FDG PET/MRI was shown to have limited sensitivity for N-staging in FIGO I/II cervical carcinoma. Therefore, this prospective study aimed to investigate the additional value of multiparametric dual-time-point PET/MRI and to assess potential influencing factors for lymph node metastasis (LNM) detection. A total of 63 patients underwent whole-body dual-time-point [18F]FDG PET/MRI 60 + 90 min p.i., and 251 LN were evaluated visually, quantified multiparametrically, and correlated with histology. Grading of the primary tumor (G2/G3) had a significant impact on visual detection (sens: 8.3%/31%). The best single parameter for LNM detection was SUVavg, however, with a significant loss of discriminatory power in G2 vs. G3 tumors (AUC: 0.673/0.901). The independent predictors SUVavg, ∆SUVpeak, LN sphericity, ADC, and histologic grade were included in the logistic-regression-based malignancy score (MS) for multiparametric analysis. Application of MS enhanced AUCs, especially in G2 tumors (AUC: G2:0.769; G3:0.877) and improved the accuracy for single LNM from 34.5% to 55.5% compared with the best univariate parameter SUVavg. Compared with visual analysis, the use of the malignancy score increased the overall sensitivity from 31.0% to 79.3% (Youden optimum) with a moderate decrease in specificity from 98.3% to 75.6%. These findings indicate that multiparametric evaluation of dual-time-point PET/MRI has the potential to improve accuracy compared with visual interpretation and enables sufficient N-staging also in G2 cervical carcinoma.

Lymph Node Staging with a Combined Protocol of 18F-FDG PET/MRI and Sentinel Node SPECT/CT: A Prospective Study in Patients with FIGO I/II Cervical Carcinoma.

Lymph node metastasis (LNM) is present in a minority of patients with early stages of cervical carcinomas. As conventional imaging including PET/CT has shown limited sensitivity, systematic lymphadenectomies are often conducted for staging purposes. Therefore, the aim of this prospective study was to analyze the impact of 18F-FDG PET/MRI in addition to sentinel lymph node (SLN) biopsy on lymph node (LN) status. Methods: Forty-two women with an initial diagnosis of Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) IA-IIB cervical carcinoma were included between March 2016 and April 2019. Each patient underwent preoperative whole-body 18F-FDG PET/MRI and SLN imaging with SPECT/CT after intracervical injection of 99mTc-labeled nanocolloid. Systematic lymphadenectomy and SLN biopsy served as the reference standard. Staging using PET/MRI was performed by nuclear medicine and radiology experts working in consensus. Results: One patient was excluded from surgical staging because of liver metastases newly diagnosed on PET/MRI. The overall prevalence of LNM in the remaining 41 patients was 29.3% (12/41). Five of 12 patients with LNM had solely small metastases with a maximum diameter of 5 mm. The consensus interpretation showed PET/MRI to have a specificity of 100% (29/29; 95% CI, 88.3%-100%) for LNM staging but a low sensitivity, 33.3% (4/12; 95% CI, 12.8%-60.9%). LN size was the most important factor for the detectability of metastases, since only LNMs larger than 5 mm could be identified by PET/MRI (sensitivity, 57.1% for >5 mm and 0% for ≤5 mm). Paraaortic LNM was evaluated accurately in 3 of the 4 patients with paraaortic LN metastasis. SLNs were detectable by SPECT/CT in 82.9% of the patients or 69.0% of the hemipelves. In cases with an undetectable SLN on SPECT/CT, the malignancy rate was considerably higher (31.2% vs. 19.3%). The combination of PET/MRI and SLN SPECT/CT improved the detection of pelvic LNM from 33.3% to 75%. Conclusion:18F-FDG PET/MRI is a highly specific N-staging method and improves LNM detection. Because of the limited sensitivity in frequently occurring small LNMs, PET/MRI should be combined with SLN mapping. The proposed combined protocol helps to decide whether extensive surgical staging is necessary in patients with FIGO I/II cervical cancer.

The Prognostic Value of Quantitative Bone SPECT/CT Before 223Ra Treatment in Metastatic Castration-Resistant Prostate Cancer.

Radiolabeled bisphosphonates such as 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) typically show intense uptake in skeletal metastases from metastatic castration-resistant prostate cancer (mCRPC). Extensive bone involvement is regarded as a risk factor for mCRPC patients treated with 223Ra-dichloride (223Ra). The aim of this study was to quantify 99mTc-DPD uptake by means of SPECT/CT before 223Ra and compare the results with the feasibility of treatment and overall survival (OS). Methods: Sixty consecutive mCRPC patients were prospectively included in this study. SPECT/CT of the central skeleton covering the skull to the mid-femoral level was performed before the first cycle of 223Ra. The bone compartment was defined by means of low-dose CT. Emission data were corrected for scatter, attenuation, and decay supplemented by resolution recovery using dedicated software. The Kaplan-Meier estimator, U test, and Cox regression analysis were used for statistics. Results: Total 99mTc-DPD uptake of the central skeleton varied between 11% and 56% of injected dose (%ID) or between 1.8 and 10.5 %ID/1,000 mL of bone volume (%ID/L). SUVmean ranged from 1.9 to 7.4, whereas the SUVmax range was 18-248. Patients unable to complete 223Ra treatment because of progression and/or cytopenia (n = 23) showed significantly higher uptake (31.9 vs. 25.4 %ID and 6.0 vs. 4.7 %ID/L; P < 0.02). OS after 223Ra (median, 15.2 mo) was reduced to 7.3 mo in cases of skeletal uptake that was 26 %ID or higher, as compared with 30.8 mo if lower than 26 %ID (P = 0.008). Similar results were obtained for %ID/L and SUVmean SUVmax did not correlate with survival. %ID/L was identified as an independent prognostic factor for OS (hazard ratio, 1.381 per unit), along with number of previous treatment lines. Conclusion: Quantitative SPECT/CT of bone scans performed at baseline is prognostic for survival in mCRPC patients treated with 223Ra.

Correlation of C-arm CT acquired parenchymal blood volume (PBV) with 99mTc-macroaggregated albumin (MAA) SPECT/CT for radioembolization work-up.

OBJECTIVE: SPECT/CT with 99mTc-macroaggregated albumin (MAA) is generally used for diagnostic work-up prior to transarterial radioembolization (TARE) to exclude shunts and to provide additional information for treatment stratification and dose calculation. C-arm CT is used for determination of lobular vascular supply and assessment of parenchymal blood volume (PBV). Aim of this study was to correlate MAA-uptake and PBV-maps in hepatocellular carcinoma (HCC) and hepatic metastases of the colorectal carcinoma (CRC). MATERIALS AND METHODS: 34 patients underwent a PBV C-arm CT immediately followed by 99mTc-MAA injection and a SPECT/CT acquisition after 1 h uptake. MAA-uptake and PBV-maps were visually assessed and semi-quantitatively analyzed (MAA-tumor/liver-parenchyma = MAA-TBR or PBV in ml/100ml). In case of a poor match, tumors were additionally correlated with post-TARE 90Y-Bremsstrahlung-SPECT/CT as a reference. RESULTS: 102 HCC or CRC metastases were analyzed. HCC presented with significantly higher MAA-TBR (7.6 vs. 3.9, p<0.05) compared to CRC. Tumors showed strong intra- and inter-individual dissimilarities between TBR and PBV with a weak correlations for capsular HCCs (r = 0.45, p<0.05) and no correlation for CRC. The demarcation of lesions was slightly better for both HCC and CRC in PBV-maps compared to MAA-SPECT/CT (exact match: 52%/50%; same intensity/homogeneity: 38%/39%; insufficient 10%/11%). MAA-SPECT/CT revealed a better visual correlation with post-therapeutic 90Y-Bremsstrahlung-SPECT/CT. CONCLUSION: The acquisition of PBV can improve the detectability of small intrahepatic tumors and correlates with the MAA-Uptake in HCC. The results indicate that 99mTc-MAA-SPECT/CT remains to be the superior method for the prediction of post-therapeutic 90Y-particle distribution, especially in CRC. However, intra-procedural PBV acquisition has the potential to become an additional factor for TARE planning, in addition to improving the determination of segment and tumor blood supply, which has been demonstrated previously.

Transitioning to whole-body SPECT/CT in prostate cancer staging: a new concept for a better imaging workflow.

AIM: Whole-body bone scan (BS) is the clinical standard in detecting bone metastases in prostate cancer patients. Additional SPECT/CT has allowed to significantly increase its diagnostic accuracy. However, performing both planar and additional SPECT/CT prolongs the total examination time and lowers patient throughput. In this study we aim to assess the diagnostic performance of a SPECT/CT-only protocol compared to the traditional procedure that is BS with a facultative SPECT/CT in case of unclear findings. METHODS: 50 patients with high-risk prostate cancer and suspected bone metastases were enrolled in this retrospective study. All patients received a whole-body Tc-99m-DPD BS followed by a 3 field-of-view (FOV) SPECT/CT (GE Discovery 670 Pro®) covering an area from the vertex to the mid-femur. Metastatic lesions were evaluated visually on BS and SPECT/CT and correlated to PSA-levels. RESULTS: Detection rate was up to 50 % higher in SPECT/CT than in BS (n = 2829 vs. n = 1942; p < 0.001), but 31/1942 (1.5 %) lesions detected on BS were located out of the SPECT/CT field-of-view. In our analysis a PSA-level of > 80 µg/l could be defined as a cut-off-value for metastatic spread beyond mid-thigh, as no patient with PSA< 80 µg/l had localizations outside the SPECT/CT field-of-view (AUCPSA = 0.95, p < 0.001 sensitivity: 100 %, specificity: 77 %, NPV: 100 %, PPV: 67 %). The SPECT/CT-only protocol did not prolong acquisition time significantly as compared to BS. CONCLUSIONS: In patients with high-risk prostate cancer presenting with PSA < 80 µg/l and absent clinical symptoms, vertex to mid-thighs 3-FOV-SPECT/CT was representative for the entire skeletal system and was able to detect more lesions than planar acquisition. This procedure did not prolong patient handling time significantly.

Automated Definition of Skeletal Disease Burden in Metastatic Prostate Carcinoma: A 3D Analysis of SPECT/CT Images.

To meet the current need for skeletal tumor-load estimation in castration-resistant prostate cancer (CRPC), we developed a novel approach based on adaptive bone segmentation. In this study, we compared the program output with existing estimates and with the radiological outcome. Seventy-six whole-body single-photon emission computed tomographies/x-ray computed tomography with 3,3-diphosphono-1,2-propanedicarboxylic acid from mCRPC patients were analyzed. The software identified the whole skeletal volume (SVol) and classified the voxels metastases (MVol) or normal bone (BVol). SVol was compared with the estimation of a commercial software. MVol was compared with manual assessment and with prostate specific antigen (PSA) levels. Counts/voxel were extracted from MVol and BVol. After six cycles of 223RaCl2-therapy every patient was re-evaluated as having progressive disease (PD), stable disease (SD), or a partial response (PR). SVol correlated with that of the commercial software (R = 0.99, p < 0.001). MVol correlated with the manually-counted lesions (R = 0.61, p < 0.001) and PSA (R = 0.46, p < 0.01). PD had a lower counts/voxel in MVol than PR/SD (715 ± 190 vs. 975 ± 215 and 1058 ± 255, p < 0.05 and p < 0.01) and BVol (PD 275 ± 60, PR 515 ± 188 and SD 528 ± 162 counts/voxel, p < 0.001). Segmentation-based tumor load correlated with radiological/laboratory indices. Uptake was linked with the clinical outcome, suggesting that metastases in PD patients have a lower affinity for bone-seeking radionuclides and might benefit less from bone-targeted radioisotope therapies.

A Prospective Study of Quantitative SPECT/CT for Evaluation of Lung Shunt Fraction Before SIRT of Liver Tumors.

The lung shunt fraction (LSF) is estimated using 99mTc-macroaggregated albumin (99mTc-MAA) imaging before selective internal radiotherapy (SIRT) of the liver to reduce the risk of pulmonary irradiation. Generally, planar scans are acquired after injection of 99mTc-MAA into the hepatic artery. However, the validity of this approach is limited by differences in attenuation between liver and lung tissue as well as inaccurate segmentation of the organs. The aim of this study was to evaluate quantitative SPECT/CT for LSF assessment in a prospective clinical cohort. Methods: Fifty consecutive patients intended to undergo SIRT were imaged within 1 h after injection of 99mTc-MAA using a SPECT/CT γ-camera. Planar scans of the lung and liver region were acquired in anterior and posterior views, followed by SPECT/CT scans of the thorax and abdomen. Emission data were corrected for scatter, attenuation, and resolution recovery using dedicated software. To quantify the radioactivity concentration in the lung, liver, urinary bladder and remainder of the thoracoabdominal body, volumes of interest were defined on the SPECT/CT images. 99mTc-MAA concentrations were calculated as percentage injected dose (%ID). Results: Mean 99mTc-MAA uptake in liver and lung accounted for only 79 %ID, whereas 13.1 %ID was present in the remainder of the body. In all patients, LSF as calculated from planar scans accounted for a median of 6.8% (range, 3.4%-32.3%), whereas the SPECT/CT quantitation revealed significantly lower LSF estimates, at a median of 1.9% (range, 0.8%-15.7%) (P < 0.0001, Wilcoxon test). On the basis of planar imaging, dose reduction or even contraindications to SIRT had to be considered in 10 of 50 patients, as their LSF was calculated at 10% or more. In contrast, SPECT/CT quantitation showed substantial shunting in only 2 of the 50 patients. Conclusion: Quantitative SPECT/CT reveals that the LSF is considerably lower than shown on planar imaging. Thus, the resulting dose to the lung parenchyma may be less than conventionally assumed. However, the safety of the SPECT/CT-derived dose range will have to be evaluated.

Tumor Burden and Intraosseous Metabolic Activity as Predictors of Bone Marrow Failure during Radioisotope Therapy in Metastasized Prostate Cancer Patients.

RATIONALE: Radium-223-Dichloride (Ra-223) is an alpha-emitter, used to treat bone metastases. Patients with high metastatic burden and/or with increased trabecular bone uptake could present a higher incidence of hematologic toxicity. We hypothesized that these two factors are predictors of bone marrow failure. MATERIAL AND METHODS: A computer algorithm discriminated between trabecular bone (BVol) and tumor metastases (MVol) within pretherapeutic whole-body skeletal SPECT/CT (N = 47). The program calculated the metastatic invasion percent (INV%) as the MVol/(MVol + BVol) ratio and extracted the BVol mean counts. BVol counts were correlated to % drop of hemoglobin (Hb), leukocytes (WBC), and platelets (PLT) after 3/6 Ra-223 cycles. Patient-specific and computational-derived parameters were tested as predictors of hematologic toxicity with MANOVA. RESULTS: BVol counts correlated with drop of Hb (R = 0,65, p < 0.01) and PLT (R = 0,45, p < 0.01). Appendicular BVol counts showed a better correlation (p < 0.05, p < 0.01, and p < 0.001 for Hb, WBC, and PLT, resp.). INV% directly correlated with BVol counts (R = 0.68, p < 0.001). At MANOVA, grade III/IV toxicity was predicted by INV% (p < 0.01), by long-bone invasion (p < 0.005), and by BVol counts (p < 0.05). CONCLUSIONS: In patients with significant bone tumor burden, degree of bone invasion and trabecular bone uptake are predictors of subsequent bone marrow failure.