scholarly journals Influence of dosimetry method on bone lesion absorbed dose estimates in PSMA therapy: application to mCRPC patients receiving Lu-177-PSMA-I&T

2020 ◽  
Author(s):  
Julia Brosch ◽  
Carlos Uribe ◽  
Astrid Gosewisch ◽  
Lena Kaiser ◽  
Andrei Todica ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Organs At Risk ◽  
Bone Lesion ◽  
Absorbed Dose ◽  
Outcome Data ◽  
Bone Lesions ◽  
Castration Resistant Prostate Cancer ◽  
Density Correction ◽  
Unit Density ◽  
Density Weighting

Abstract Background Patients with metastatic, castration-resistant prostate cancer (mCRPC) present with an increased tumor burden in the skeleton. For these patients, Lutetium-177 (Lu-177) radioligand therapy targeting the prostate-specific membrane antigen (PSMA) has gained increasing interest with promising outcome data. Patient-individualized dosimetry enables quantification of therapy success with the aim of minimizing absorbed dose to organs at risk while maximizing absorbed dose to tumors. Different dosimetric approaches with varying complexity and accuracy exist for this purpose. The relatively simple OLINDA method applied to tumors assumes a homogeneous activity distribution in a sphere with unit density. Voxel S value (VSV) approaches can account for heterogeneous activities but are simulated for a specific tissue. Full patient-individual Monte Carlo (MC) dose simulation addresses both, heterogeneous activity and density distributions. Subsequent CT-based density correction has the potential to overcome the assumption of homogeneous density in OLINDA and VSV methods, which could be a major limitation for the application in bone metastases with heterogeneous density. The aim of this investigation is a comparison of these methods for bone lesion dosimetry in mCRPC patients receiving Lu-177-PSMA therapy. Results In total, 289 bone lesions in 15 mCRPC patients were analyzed. Percentage deviation (PD) of absorbed lesion doses compared to full MC was + 7 ± 13% (min: -60%; max: +47%) for the OLINDA unit density sphere model. With an applied CT-based density weighting to account for density differences in bone lesions, PD was − 15 ± 6% (min: -54%; max: -2%). For a soft tissue VSV approach, large PDs of + 16 ± 13% (min: -56%; max: +57%) were found; after voxel-wise density correction this was reduced to -5 ± 2% (min: -15%; max: -2%). The use of a combination of standard soft tissue and cortical bone VSVs showed deviations of -35 ± 8% (min: -76%; max: +5%). With additional voxel-wise density weighting, the PD was − 3 ± 2% (min: -13%; max: 0%). Conclusion Based on our bone lesion dosimetry results, a VSV approach with subsequent CT-based, voxel-wise density correction enabled dose estimates, that closely replicate computationally-demanding gold-standard full MC dose simulations.

scholarly journals Influence of dosimetry method on bone lesion absorbed dose estimates in PSMA therapy: application to mCRPC patients receiving Lu-177-PSMA-I&T

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Julia Brosch-Lenz ◽  
Carlos Uribe ◽  
Astrid Gosewisch ◽  
Lena Kaiser ◽  
Andrei Todica ◽  
...  
Keyword(s):  
Organs At Risk ◽  
Bone Lesion ◽  
Absorbed Dose ◽  
Hounsfield Unit ◽  
Outcome Data ◽  
Computational Effort ◽  
Bone Lesions ◽  
Castration Resistant Prostate Cancer ◽  
Percentage Difference ◽  
Density Weighting

Abstract Background Patients with metastatic, castration-resistant prostate cancer (mCRPC) present with an increased tumor burden in the skeleton. For these patients, Lutetium-177 (Lu-177) radioligand therapy targeting the prostate-specific membrane antigen (PSMA) has gained increasing interest with promising outcome data. Patient-individualized dosimetry enables improvement of therapy success with the aim of minimizing absorbed dose to organs at risk while maximizing absorbed dose to tumors. Different dosimetric approaches with varying complexity and accuracy exist for this purpose. The Medical Internal Radiation Dose (MIRD) formalism applied to tumors assumes a homogeneous activity distribution in a sphere with unit density for derivation of tumor S values (TSV). Voxel S value (VSV) approaches can account for heterogeneous activities but are simulated for a specific tissue. Full patient-individual Monte Carlo (MC) absorbed dose simulation addresses both, heterogeneous activity and density distributions. Subsequent CT-based density weighting has the potential to overcome the assumption of homogeneous density in the MIRD formalism with TSV and VSV methods, which could be a major limitation for the application in bone metastases with heterogeneous density. The aim of this investigation is a comparison of these methods for bone lesion dosimetry in mCRPC patients receiving Lu-177-PSMA therapy. Results In total, 289 bone lesions in 15 mCRPC patients were analyzed. Percentage difference (PD) of average absorbed dose per lesion compared to MC, averaged over all lesions, was + 14 ± 10% (min: − 21%; max: + 56%) for TSVs. With lesion-individual density weighting using Hounsfield Unit (HU)-to-density conversion on the patient’s CT image, PD was reduced to − 8 ± 1% (min: − 10%; max: − 3%). PD on a voxel level for three-dimensional (3D) voxel-wise dosimetry methods, averaged per lesion, revealed large PDs of + 18 ± 11% (min: − 27%; max: + 58%) for a soft tissue VSV approach compared to MC; after voxel-wise density correction, this was reduced to − 5 ± 1% (min: − 12%; max: − 2%). Conclusion Patient-individual MC absorbed dose simulation is capable to account for heterogeneous densities in bone lesions. Since the computational effort prevents its routine clinical application, TSV or VSV dosimetry approaches are used. This study showed the necessity of lesion-individual density weighting for TSV or VSV in Lu-177-PSMA therapy bone lesion dosimetry.

The clinical impact of bone scan (BS) flare with enzalutamide (ENZA) in men with metastatic castration-resistant prostate cancer (mCRPC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 183-183
Author(s):  
Andrew J. Armstrong ◽  
Mohammed Al-Adhami ◽  
Ping Lin ◽  
Teresa Parli ◽  
Jennifer Sugg ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Clinical Impact ◽  
Adverse Outcomes ◽  
Bone Lesions ◽  
Castration Resistant Prostate Cancer ◽  
Two Phase ◽  
Castration Resistant ◽  
Slow Progression ◽  
Tissue Responses

183 Background: Current PCWG3 guidelines for men with mCRPC define BS progression during therapy as requiring confirmation of new bone lesions that develop over time with additional new lesions. New unconfirmed BS lesions may reflect slow progression or a favorable osteoblastic reaction called a “BS flare” that can be misinterpreted as radiographic progression and lead to premature therapy discontinuation. The prevalence and clinical impact of BS flare is unknown for ENZA. Methods: We analyzed the association of BS flare with clinical outcomes and quality of life (QoL) in a retrospective analysis of two phase 3 trials of men with mCRPC treated with ENZA after (AFFIRM n = 1199) and before (PREVAIL n = 1717) docetaxel. Early and late BS flare was defined as new lesions on the first posttreatment BS (weeks 9-13) or subsequent BS, respectively, that were not confirmed to meet progression criteria on the next BS, while also requiring responding/stable PSA and soft-tissue disease. Results: Unconfirmed BS lesions were observed in 22% and 25% of stable/responding men receiving ENZA in AFFIRM and PREVAIL, respectively. Most BS flares were early, but late flares (week 17 or later) were seen in 2% and 13% of men, respectively. Unconfirmed BS lesions (early or late) had no impact on OS (HR 0.87; 95% CI 0.62-1.21) or rPFS (HR 0.91; 95% CI 0.58-1.44) in PREVAIL, but were associated with worse OS (HR 2.26; 95% CI 1.55-3.30) and rPFS (HR 1.73; 95% CI 1.33-2.26) in AFFIRM. Soft-tissue responses and PSA declines were more prominent in chemo-naïve men with unconfirmed BS lesions, which also had no impact on QoL or pain deterioration in either setting. Conclusions: BS flare occurred in ≈25% of responding men with mCRPC receiving ENZA and was not associated with adverse outcomes in chemo-naïve men. Our findings support the importance of avoiding premature treatment discontinuation in the presence of unconfirmed new BS lesions in the first 4 months of therapy. Worse outcomes associated with unconfirmed lesions in men post docetaxel illustrate the need for improved functional bone imaging in mCRPC and broader patient assessment to decide on treatment continuation. Clinical trial information: NCT00974311; NCT01212991.

Tumor-directed PET imaging of metastases in metastatic castration-resistant prostate cancer (mCRPC) using Zr-89 labeled antiprostate-specific membrane antigen (PSMA) antibody J591.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 164-164
Author(s):  
Jarett L. Feldman ◽  
Michael J. Morris ◽  
Scott T. Tagawa ◽  
David M. Nanus ◽  
Stephen Barnett Solomon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Soft Tissue ◽  
Pet Imaging ◽  
Response Assessment ◽  
Imaging Modalities ◽  
Bone Lesions ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
External Domain ◽  
Clinical Trial Information

164 Background: There is no standard imaging (SI) modality that specifically and accurately images prostate cancer (PC) metastases, hampering prognostication and response assessment. J591 is a humanized antibody that targets the external domain of PSMA. We have previously reported on the feasibility, PK and biodistribution properties of 89Zr-J591 in 10 patients (pts) (Pandit-Taskar et al, Eur J Nuc Med Img 2014). We now report on the targeting/accuracy in 50 pts with mCRPC. Methods: Following standard CT/MRI, bone scan (BS), and FDG PET imaging, 5 mCi of 89Zr-J591 was administered IV. 89Zr-J591 was imaged 6-8 days after injection. Positive (pos) scan findings were confirmed, where possible, with biopsies (bxs) in the following preference: concordant 89Zr-J591 and FDG pos, 89Zr-J591 and FDG mismatch, and a mismatch between SI and any PET. Results: Imaging: A total of 703 lesions in 50 pts were identified using all imaging modalities. Bone:538 total bone lesions were detected. 491(91%) lesions were present on J591 of which 99 were only evident by J591. BS identified 339 (63%), CT 301 (56%), and FDG 207 (38%). Soft Tissue: 165 total soft tissue lesions were detected. 90 (55%) were seen on J591 of which 17 were only evident by J591. CT identified 124 (75%) and FDG 88 (53%). Pathology:46 bx’s were evaluable (21 bone, 25 soft tissue) in 34 pts. Of the unique J591 lesions biopsied (bx’d), 5/7 were pos for PC. Bone: We bx’d 19 J591 pos lesions and 2 J591 neg sites. Overall, path concordance with J591 was: 89% true pos, 100% true neg, 11% false pos, and 0% false neg. Soft tissue: We bx’d 16 J591 pos lesions and 9 J591 neg sites. Of these, we found 88% true pos, 11% true neg, 13% false pos, and 89% false neg. Conclusions: J591 PET identifies additional disease in bone not seen using other imaging modalities. These lesions are highly likely to correspond to disease by bx. However, the tracer performed less well in soft tissue, with a high false neg rate. Clinical trial information: NCT01543659.

scholarly journals Diagnostic Value of Whole-Body MRI Short Protocols in Bone Lesion Detection in Multiple Myeloma Patients

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1053
Author(s):  
Davide Ippolito ◽  
Teresa Giandola ◽  
Cesare Maino ◽  
Davide Gandola ◽  
Maria Ragusi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow Involvement ◽  
Bone Lesion ◽  
Diagnostic Value ◽  
Lesion Detection ◽  
Lower Limbs ◽  
Whole Body ◽  
Bone Lesions ◽  
Whole Body Mri ◽  
Mri Protocol

The aim of the study is to evaluate the effectiveness of short whole-body magnetic resonance imaging (WBMRI) protocols for the overall assessment of bone marrow involvement in patients with multiple myeloma (MM), in comparison with standard whole-body MRI protocol. Patients with biopsy-proven MM, who underwent a WBMRI with full-body coverage (from vertex to feet) were retrospectively enrolled. WBMRI images were independently evaluated by two expert radiologists, in terms of infiltration patterns (normal, focal, diffuse, and combined), according to location (the whole skeleton was divided into six anatomic districts: skull, spine, sternum and ribs, upper limbs, pelvis and proximal two-thirds of the femur, remaining parts of lower limbs) and lytic lesions number (<5, 5–20, and >20). The majority of patients showed focal and combined infiltration patterns with bone lesions predominantly distributed in the spine and pelvis. As skull and lower limbs are less frequently involved by focal bone lesions, excluding them from the standard MRI protocol allows to obtain a shorter protocol, maintaining a good diagnostic value.

Reconstruction of Extensive Soft Tissue Defects of Lower Extremity With the Extended Anterolateral Thigh Flap

2021 ◽  
pp. 153473462098223
Author(s):  
Jong-Ho Kim ◽  
Hyokyung Yoo ◽  
Seokchan Eun
Keyword(s):  
Soft Tissue ◽  
Lower Extremity ◽  
Distal Portion ◽  
Outcome Data ◽  
Anterolateral Thigh Flap ◽  
Soft Tissue Defects ◽  
Flap Viability ◽  
Anterolateral Thigh ◽  
Large Skin ◽  
Tissue Defects

The anterolateral thigh flap is a classic flap used for various reconstruction defects. However, the flap viability of extended large skin paddles (ie, 240 cm2) was doubted by many surgeons. This study reports successful experience of reconstructing extensive soft tissue defects of lower extremity using extended large skin paddles. Twelve consecutive patients who had undergone reconstruction of defects using an extended anterolateral thigh flap were identified. Patient characteristics (age, sex, defect location, injured structures, and type of flap) and outcome data were analyzed retrospectively. One artery and 2 accompanying veins were anastomosed to vascularize each flap. Follow-up periods ranged from 10 to 91 months postoperatively. The average size of the flaps was 268.75 cm2 (range = 220-391 cm2). All flaps were perforator flaps with one perforator except that 2 perforators were used in 3 patients. Two patients suffered partial flap necrosis of the distal portion with delayed healing. In conclusion, the extended anterolateral thigh flap is a considerable option for massive defects requiring composite tissue coverage. This flap is advantageous for reconstructing various complex defects in the lower extremities, providing a pliable and vascularized tissue to cover exposed extensive defects including tendons, nerves, and bones.

scholarly journals Use of a Head-Tilting Baseplate During Tomotherapy to Shorten the Irradiation Time and Protect the Hippocampus and Lens in Hippocampal Sparing-Whole Brain Radiotherapy

2021 ◽  
Vol 20 ◽  
pp. 153303382098682
Author(s):  
Kosei Miura ◽  
Hiromasa Kurosaki ◽  
Nobuko Utsumi ◽  
Hideyuki Sakurai
Keyword(s):  
At Risk ◽  
Planning Target Volume ◽  
Irradiation Time ◽  
Organs At Risk ◽  
Absorbed Dose ◽  
Whole Brain Radiotherapy ◽  
Target Volume ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Hippocampal Sparing

Purpose: The aim of this study is to comparatively examine the possibility of reducing the exposure dose to organs at risk, such as the hippocampus and lens, and improving the dose distribution of the planned target volume with and without the use of a head-tilting base plate in hippocampal-sparing whole-brain radiotherapy using tomotherapy. Methods: Five paired images of planned head computed tomography without and with tilt were analyzed. The hippocampus and planning target volume were contoured according to the RTOG 0933 contouring atlas protocol. The hippocampal zone to be avoided was delineated using a 5-mm margin. The prescribed radiation dose was 30 Gy in 10 fractions. The absorbed dose to planning target volume dose, absorbed dose to the organ at risk, and irradiation time were evaluated. The paired t-test was used to analyze the differences between hippocampal-sparing whole-brain radiotherapy with head tilts and without head tilts. Results: Hippocampal-sparing whole-brain radiotherapy with tilt was not superior in planning target volume doses using the homogeneity index than that without tilt; however, it showed better values, and for Dmean and D2%, the values were closer to 30 Gy. Regarding the hippocampus, dose reduction with tilt was significantly greater at Dmax, Dmean, and Dmin, whereas regarding the lens, it was significantly greater at Dmax and Dmin. The irradiation time was also predominantly shorter. Conclusion: In our study, a tilted hippocampal-sparing whole-brain radiotherapy reduced the irradiation time by >10%. Therefore, our study indicated that hippocampal-sparing whole-brain radiotherapy with tomotherapy should be performed with a tilt. The head-tilting technique might be useful during hippocampal-sparing whole-brain radiotherapy. This method could decrease the radiation exposure time, while sparing healthy organs, including the hippocampus and lens.

scholarly journals Comparison of PSMA PET/CT With Fluoride PET/CT for Detection of Bone Metastatic Disease in Prostate Cancer

2021 ◽  
Author(s):  
Naresh Kumar Regula ◽  
Vasileios Kostaras ◽  
Silvia Johansson ◽  
Carlos Trampal ◽  
Elin Lindström ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lymph Node ◽  
Bone Metastasis ◽  
Soft Tissue ◽  
Diagnostic Performance ◽  
Bone Lesions ◽  
Soft Tissue Lesions ◽  
Contrast Enhanced Ct ◽  
Psma Pet ◽  
Pet Ct

Abstract 18F-NaF positron emission tomography/computed tomography (fluoride PET/CT) is considered the most sensitive technique to detect bone metastasis in prostate cancer (PCa). 68Ga-PSMA-11 (PSMA) PET/CT is increasingly used for staging of PCa. This study primarily aimed to compare the diagnostic performance of fluoride PET/CT and Gallium based PSMA PET/CT in identifying bone metastasis followed by a comparison of PSMA PET/CT with contrast-enhanced CT (CE-CT) in identifying soft tissue lesions as a secondary objective. Methods: Twenty-eight PCa patients with high suspicion of disseminated disease following curative treatment were prospectively evaluated. PET/CT examinations using fluoride and PSMA were performed. All suspicious bone lesions were counted, and the tracer uptake was measured as standardized uptake values (SUV) for both tracers. In patients with multiple findings, ten bone lesions with highest SUVmax were selected from which identical lesions from both scans were considered for direct comparison of SUVmax. Soft tissue findings of local and lymph node lesions from CE-CT were compared with PSMA PET/CT. Results: Both scans were negative for bone lesions in 7 patients (25%). Of 699 lesions consistent with skeletal metastasis in 21 patients on fluoride PET/CT, PSMA PET/CT identified 579 lesions (83%). In 69 identical bone lesions fluoride PET/CT showed significantly higher uptake (mean SUVmax: 73.1±36.8) compared to PSMA PET/CT (34.5±31.4; p<0.001). Compared to CE-CT, PSMA PET/CT showed better diagnostic performance in locating local (96% vs 61%, p=0.004) and lymph node (94% vs 46%, p<0.001) metastasis. Conclusion: In this prospective comparative study PSMA PET/CT detected the majority of bone lesions that were positive on fluoride PET/CT. Further, this study indicates better diagnostic performance of PSMA PET/CT to locate soft tissue lesions compared to CE-CT.

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