High-Dose Samarium-153 Ethylene Diamine Tetramethylene Phosphonate: Low Toxicity of Skeletal Irradiation in Patients With Osteosarcoma and Bone Metastases

2002 ◽  
Vol 20 (1) ◽  
pp. 189-196 ◽  
Author(s):  
Peter M. Anderson ◽  
Gregory A. Wiseman ◽  
Angela Dispenzieri ◽  
Carola A.S. Arndt ◽  
Lynn C. Hartmann ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Performance Status ◽  
Bone Cancer ◽  
Ethylene Diamine ◽  
Whole Body ◽  
Skeletal Metastases ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Marrow Infusion ◽  
Therapeutic Irradiation

PURPOSE: Samarium-153 ethylene diamine tetramethylene phosphonate (153Sm-EDTMP), a bone-seeking radiopharmaceutical, provides therapeutic irradiation to osteoblastic bone metastases. Because the dose-limiting toxicity of 153Sm-EDTMP is thrombocytopenia, a dose-escalation trial using peripheral-blood progenitor cells (PBPCs) or marrow support was conducted to treat metastatic bone cancer. PATIENTS AND METHODS: Patients with locally recurrent or metastatic osteosarcoma or skeletal metastases avid on bone scan were treated with 1, 3, 4.5, 6, 12, 19, or 30 mCi/kg of 153Sm-EDTMP. RESULTS: Thirty patients were treated with 153Sm-EDTMP. Transient symptoms of hypocalcemia were seen at 30 mCi/kg. Estimates of radioisotope bound to bone surfaces and marrow radiation dose were linear with injected amount of 153Sm-EDTMP. Cytopenias also occurred in all subjects and were dose-related. At day +13 after 153Sm-EDTMP, residual whole-body radioactivity was 1% to 65% of whole-body radioactivity considered safe for PBPC infusion, 3.6 mCi. After PBPC or marrow infusion on day +14 after 153Sm-EDTMP, recovery of hematopoiesis was problematic in two patients at the 30 mCi/kg dose infused with less than 2 × 106 CD34+/kg on day +14, but not in other patients. Reduction or elimination of opiates for pain was seen in all patients. Patients had no adverse changes in appetite or performance status. CONCLUSION: 153Sm-EDTMP with PBPC support can provide bone-specific therapeutic irradiation (estimates of 39 to 241 Gy). Hematologic toxicity at 30 mCi 153Sm-EDTMP/kg requires PBPC grafts with more than 2 × 106 CD34+/kg to overcome myeloablative effects of skeletal irradiation. Nonhematologic side effects are minimal.

Hematologic Toxicity of High-Dose Iodine-131–Metaiodobenzylguanidine Therapy for Advanced Neuroblastoma

2004 ◽  
Vol 22 (12) ◽  
pp. 2452-2460 ◽  
Author(s):  
Steven G. DuBois ◽  
Julia Messina ◽  
John M. Maris ◽  
John Huberty ◽  
David V. Glidden ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Radiation Dose ◽  
Red Cells ◽  
Whole Body ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Severe Thrombocytopenia ◽  
Hematopoietic Stem ◽  
Iodine 131 ◽  
Mibg Therapy

Purpose Iodine-131–metaiodobenzylguanidine (131I-MIBG) has been shown to be active against refractory neuroblastoma. The primary toxicity of 131I-MIBG is myelosuppression, which might necessitate autologous hematopoietic stem-cell transplantation (AHSCT). The goal of this study was to determine risk factors for myelosuppression and the need for AHSCT after 131I-MIBG treatment. Patients and Methods Fifty-three patients with refractory or relapsed neuroblastoma were treated with 18 mCi/kg 131I-MIBG on a phase I/II protocol. The median whole-body radiation dose was 2.92 Gy. Results Almost all patients required at least one platelet (96%) or red cell (91%) transfusion and most patients (79%) developed neutropenia (< 0.5 × 103/μL). Patients reached platelet nadir earlier than neutrophil nadir (P < .0001). Earlier platelet nadir correlated with bone marrow tumor, more extensive bone involvement, higher whole-body radiation dose, and longer time from diagnosis to 131I-MIBG therapy (P ≤ .04). In patients who did not require AHSCT, bone marrow disease predicted longer periods of neutropenia and platelet transfusion dependence (P ≤ .03). Nineteen patients (36%) received AHSCT for prolonged myelosuppression. Of patients who received AHSCT, 100% recovered neutrophils, 73% recovered red cells, and 60% recovered platelets. Failure to recover red cells or platelets correlated with higher whole-body radiation dose (P ≤ .04). Conclusion These results demonstrate the substantial hematotoxicity associated with high-dose 131I-MIBG therapy, with severe thrombocytopenia an early and nearly universal finding. Bone marrow tumor at time of treatment was the most useful predictor of hematotoxicity, whereas whole-body radiation dose was the most useful predictor of failure to recover platelets after AHSCT.

scholarly journals Detection and Segmentation of Pelvic Bones Metastases in MRI Images for Patients With Prostate Cancer Based on Deep Learning

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiang Liu ◽  
Chao Han ◽  
Yingpu Cui ◽  
Tingting Xie ◽  
Xiaodong Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Deep Learning ◽  
Bone Metastases ◽  
Model Development ◽  
Whole Body ◽  
Pelvic Bone ◽  
Skeletal Metastases ◽  
Dice Similarity Coefficient ◽  
Patient Level ◽  
Lesion Level

ObjectiveTo establish and evaluate the 3D U-Net model for automated segmentation and detection of pelvic bone metastases in patients with prostate cancer (PCa) using diffusion-weighted imaging (DWI) and T1 weighted imaging (T1WI) images.MethodsThe model consisted of two 3D U-Net algorithms. A total of 859 patients with clinically suspected or confirmed PCa between January 2017 and December 2020 were enrolled for the first 3D U-Net development of pelvic bony structure segmentation. Then, 334 PCa patients were selected for the model development of bone metastases segmentation. Additionally, 63 patients from January to May 2021 were recruited for the external evaluation of the network. The network was developed using DWI and T1WI images as input. Dice similarity coefficient (DSC), volumetric similarity (VS), and Hausdorff distance (HD) were used to evaluate the segmentation performance. Sensitivity, specificity, and area under the curve (AUC) were used to evaluate the detection performance at the patient level; recall, precision, and F1-score were assessed at the lesion level.ResultsThe pelvic bony structures segmentation on DWI and T1WI images had mean DSC and VS values above 0.85, and the HD values were &lt;15 mm. In the testing set, the AUC of the metastases detection at the patient level were 0.85 and 0.80 on DWI and T1WI images. At the lesion level, the F1-score achieved 87.6% and 87.8% concerning metastases detection on DWI and T1WI images, respectively. In the external dataset, the AUC of the model for M-staging was 0.94 and 0.89 on DWI and T1WI images.ConclusionThe deep learning-based 3D U-Net network yields accurate detection and segmentation of pelvic bone metastases for PCa patients on DWI and T1WI images, which lays a foundation for the whole-body skeletal metastases assessment.

Phase I study of repeated cycles of high-dose cyclophosphamide, etoposide, and cisplatin administered without bone marrow transplantation.

1990 ◽  
Vol 8 (10) ◽  
pp. 1728-1738 ◽  
Author(s):  
J A Neidhart ◽  
W Kohler ◽  
C Stidley ◽  
A Mangalik ◽  
A Plauche ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase I ◽  
Performance Status ◽  
Complete Response ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Tumor Type ◽  
Advanced Malignancy ◽  
Prior Therapy ◽  
And Performance

Forty-two patients with advanced malignancy judged unlikely to respond to standard treatment received high-dose combination chemotherapy with cyclophosphamide, etoposide, and cisplatin in a phase I trial. Twenty-two of these patients who had at least a partial response (PR) to the first cycle of therapy received a second cycle, and eight patients received three or more cycles of therapy. Bone marrow replacement was not used. The maximum-tolerated doses (MTDs) were cyclophosphamide 2.5 g/m2 on days 1 and 2; etoposide 500 mg/m2 on days 1, 2, and 3; and cisplatin 50 mg/m2 on days 1, 2, and 3. Hematologic toxicity was not dose-limiting by study design. Recovery to an absolute granulocyte count above 100/microL occurred at a median of 9 days from onset (range, 3 to 23 days) at the MTD. Recovery was delayed after the third cycle. Only one patient on his third cycle failed to recover peripheral blood counts and died of sepsis an day 43. Hematologic toxicity was not dose-dependent. Nonhematologic toxicities included emesis, fatigue, alopecia, diarrhea, and anorexia and were generally well tolerated. The dose-limiting toxicities were fatal pulmonary or cardiac toxicities in five of nine patients treated at the highest dose level. Patients likely to do well can be selected by tumor type, response to prior therapy, and performance status. Nine of 36 assessable patients had a complete response (CR) and 13 a PR for a response rate of 61%. Five patients (12%) remain alive and free of disease at 15 to 32 months. Repeated cycles of dose-intensive combination therapy can produce long-term disease-free remissions in patients with refractory tumor types. The toxicity of the regimen is acceptable if patients are carefully selected.

scholarly journals SURVIVAL IMPACT OF SKELETAL METASTASIS ON BONE SCINTIGRAPHY IN PATIENTS WITH GERM CELL TUMOURS

2016 ◽  
Vol 2 (4) ◽  
Author(s):  
Maimoona Siddique ◽  
Aamna Hassan ◽  
Saadiya J Khan
Keyword(s):  
Germ Cell ◽  
Bone Metastases ◽  
Bone Scintigraphy ◽  
Bone Scan ◽  
Disease Free Survival ◽  
Skeletal Metastasis ◽  
Whole Body ◽  
Skeletal Metastases ◽  
Germ Cell Tumours ◽  
Visceral Metastases

Objective: Our aim was to determine the frequency of skeletal metastasis in germ cell tumours (GCT) at baseline and relapse on conventional technetium-99m methylene diphosphonate (Tc-99m MDP) whole body bone scan (bone scan) and to evaluate the effect of bone metastases on survival. Materials and Methods: Electronic medical records of histologically proven GCT over 64 months were retrospectively analysed. Basic demographic and histologic information were correlated with the presence of osseous and visceral metastases. 5-year disease-free survival (DFS) and overall survival (OS) were calculated in presence, the absence of bone metastases at baseline and at relapse. Results: A total of 130 gonadal and extragonadal GCT patients underwent Tc-99m MDP bone scans; four with insuf cient data were excluded from the study. 47% were females and 53% were males with the age range of 1 month – 72 years. 105 (83%) were under 18 years of age. Osseous metastasis was detected in 12 (9.5%). Two (17%) had solitary and 10 (83%) had multifocal skeletal metastases. Clinically, 83% had localised bone pain. Osseous metastases were more frequently associated with mixed GCT and yolk sac tumour. 50% of mediastinal GCT developed bone metastases. 42% died within 4–18 months. There was a statistically signi cant impact of visceral metastases on DFS and OS. OS at 5 years in patients without bone metastases, with bone metastases at baseline and bone metastases at relapse, was 77%, 38% and 75%, respectively. 5-year DFS for the same cohort groups was 63%, 38% and 20%, respectively. Conclusion: Osseous involvement was found in 9.5% of GCT patients undergoing diagnostic Tc-99m MDP bone scan. Baseline skeletal evaluation for metastases should be done, particularly in the case of bone pains or known systemic metastases. Although skeletal relapses are rare, they have a grim outcome. Key words: Bone scintigraphy, germ cell tumours, skeletal metastases 

153Sm-EDTMP and 177Lu-EDTMP are equally safe and effective in pain palliation from skeletal metastases

2018 ◽  
Vol 57 (05) ◽  
pp. 174-180 ◽  
Author(s):  
Mehrdad Taheri ◽  
Zahra Azizmohammadi ◽  
Mojtaba Ansari ◽  
Payman Dadkhah ◽  
Kasra Dehghan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Pain Intensity ◽  
Functional Status ◽  
Phosphonic Acid ◽  
Performance Status ◽  
Ethylene Diamine ◽  
Skeletal Metastases ◽  
Ecog Performance Status ◽  
Double Blind

Summary Introduction: Bone pain from multifocal blastic or mixed lytic-blastic metastatic lesions can be effectively addressed with radiopharmaceuticals with high affinity for such foci. 153Sm-ethylene diamine tetramethylene phosphonic acid (153Sm-EDTMP) and 177Lu-ethylene diamine tetramethylene phosphonic acid) (177Lu-EDTMP) are two such radiopharmaceuticals. The aim of this study was to make a comparison of efficacy between 153Sm-EDTMP and 177Lu-EDTMP in terms of palliation of commonly encountered symptoms in cancer patients, functional status, and pain intensity as measured by Edmonton Symptom Assessment System (ESAS), Eastern Cooperative Oncology Group (ECOG) performance status, and numeric rating scale (NRS) respectively. This study was a double blind randomized clinical trial conducted in a setting of three university hospitals. Materials and Methods: In a randomized double-blind clinical trial 50 patients will with documented painful bone metastases of blastic or mixed lytic-blastic nature were randomly allocated into two groups; group receiving 153Sm-EDTMP and group receiving 177Lu-EDTMP. Radiopharmaceuticals were given at a dose of 37.0 MBq / kg body weight in both groups. Scores on ESAS, ECOG performance status and NRS were recorded before the intervention and following the intervention at 2, 4, 6, and 12 weeks. Hematologic toxicity was evaluated by monitoring hematologic parameters at the baseline and at 1, 3, 6, and 8 weeks after the intervention.Results: Fifty patients, 31 (62 %) females and 19 (38 %) males with the mean age of 66.08 ± 4.53 years were recruited. The baseline means and standard deviations for pain intensity as measured by the NRS were 8.4 ± 1.47 and 8.36 ± 1.43 in 153Sm-EDTMP- and 177Lu-EDTMP-treated subjects respectively. Patients of both groups showed significant alleviation of pain observed from the 2nd week (first follow up session) and continuing to the 12th week after treatment . No difference in response to the two radiopharmaceuticals were seen regarding their efficacy in pain alleviation (P < 1.0). Baseline “symptom distress scores” drawn from the ESAS-r in 153Sm-EDTMP- and 177Lu-EDTMP-treated groups were 5.5 ± 2.1 and 5.4 ± 2.1, respectively. The scores significantly improved in both groups with the most marked rate of improvement achieved within the first two weeks after treatment. The scores continued to improve until the 12th week of follow-up (P < 1.0, non-significant [ns]). Functional status as measured by ECOG performance status scores improved in both groups over the follow up period. Baseline scores on ECOG performance status in 153Sm-EDTMP- and 177Lu-EDTMP-treated groups were 2.5 ± 1.3 and 2.5 ± 1.3 (mean ± standard deviation). At 3 months post-treatment scores improved to 1.6 ± 0.6 and 1.6 ± 0.6 respectively (P < 1.0, n.s.). Conclusions: 153Sm-EDTMP and 177Lu-EDTMP are safe and effective radiopharmaceuticals in palliation of cancer pain from multiple skeletal metastases of blastic and mixed lyticblastic nature.

Intensive Timed Sequential Chemotherapy Followed by a Single Pegfilgrastim (Neulasta) Administration in Patients with High-Risk Acute Myeloid Leukemia (AML): Preliminary Results of the EMA-2000/Neu Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4558-4558
Author(s):  
Xavier Thomas ◽  
Youcef Chelghoum ◽  
Anne Thiebaut ◽  
Mohamed Elhamri ◽  
Emmanuelle Tavernier ◽  
...  
Keyword(s):  
High Risk ◽  
Complete Remission ◽  
Median Time ◽  
Performance Status ◽  
Response To Therapy ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Sequential Chemotherapy ◽  
Who Grade ◽  
Platelet Recovery

Abstract Following a dose-escalation study performed in order to assess the maximally tolerated dose of high-dose mitoxantrone in a single injection (45mg/m2) combined with timed-sequential chemotherapy, a phase II trial (EMA-2000 regimen) was performed in high-risk AML. EMA-2000 regimen was effective (complete remission: 63%), but extra-hematologic toxicity appeared very high (53% of severe infections). In order to decrease toxicity, the same regimen was proposed between February 2004 and May 2006 followed by a single administration of Pegfilgrastim. Twenty-four patients entered the study and received mitoxantrone 45 mg/m2 on day 1 in combination with cytarabine (500 mg/m2 on days 1 to 3 and 8 to 10) and etoposide (200 mg/m2 on days 8 to 10) followed (after checking for the absence of blast in bone marrow aspirate performed at day 11) at day 12 by 6 mg of Pegfilgrastim administered by subcutaneous route. Overall, 15 patients (63%) achieved complete remission (CR) and 9 patients had resistant disease. Median time to achieve CR was 43 days. CR achievement was related to leukemia stage [50% (2/4 patients) in refractory AML and 65% (13/20 patients) in relapsed AML]. Median time to granulocyte recovery &gt; 0.5 × 109/l was 28 days. Median time to platelet recovery &gt; 50 × 109/l was 30 days. The predominant non-hematologic toxicity remained infections with 54% of septicemia and 62% of localized infections. Other severe extra-hematologic toxicity (WHO grade &gt; 2) were mucositis (50%), nausea and vomiting (33%), and diarrhea (17%). Pegfilgrastim was well tolerated. Nine of the 15 remitters received subsequent treatment consisting of maintenance chemotherapy courses in 3 patients, allogeneic stem cell transplantation (SCT) in 3 patients, and autologous SCT in 3 patients. Median DFS was 11.5 months with an estimated 2-year DFS rate of 37%. DFS was related to first CR duration (p = 0.01). Median OS was 12.5 months with a 2-year OS rate of 32%. Response to therapy, toxicity and survival were compared to those of our previous EMA-2000 regimen. Patient populations were matched on age, leukemia stage, performance status, and FAB subtypes. Outcome was similar regarding CR rate and extra-hematologic toxicity. Neutrophil and platelet recovery was only 2 days and 4 days shorter with the new regimen. However median DFS and OS, and 2-year survival estimate appeared better with the new regimen (11.5 months with 37% 2-year DFS vs 7.2 months with 16%; and 12.5 months with 32% vs 8.1 months with 18% respectively). This was confirmed whatever was the result of induction therapy. In patients achieving CR, median OS was 18.4 months with 61% 1-year OS vs 9.3 months with 36%, while in patients with no CR, median OS was 9.7 months with 44% 1-year OS vs 3.7 months with 8%. These results suggest a potential differentiating or immune-regulating effect of Pelfilgrastim. None of the patients with initial hyperleukocytosis (&gt; 10 × 109/l), who failed to achieve CR, recovered on a hyperleukocytosic mode. Biological explorations and a randomized study are warranted for confirming our results.

scholarly journals Diagnostic Value of PET/MR with DWI for Burkitt Lymphoma

Diagnostics ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1867
Author(s):  
Chiara Giraudo ◽  
Rossella Simeone ◽  
Margherita Fosio ◽  
Dario Marino ◽  
Diego Cecchin
Keyword(s):  
Burkitt Lymphoma ◽  
Metabolic Response ◽  
Diagnostic Value ◽  
Whole Body ◽  
Skeletal Metastases ◽  
High Dose ◽  
Bone Marrow Biopsies ◽  
Complete Metabolic Response ◽  
Whole Body Ct ◽  
Tertiary Center

18F-FDG-PET/MR images, including DWI, of a 46-year-old male admitted to the Emergency Room of our tertiary center, who was suffering from diplopia, left orbital pain, and a headache for two weeks, demonstrated multiple hepatic nodules, a pancreatic mass, and skeletal metastases, in addition to thrombosis of the left cavernous sinus, thickening of the small intestine, and a large hepatic lesion identified at head and neck MR and whole-body CT, respectively. Hepatic and bone marrow biopsies revealed the diagnosis of Burkitt lymphoma. After four cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, and high dose cytarabine (R- CODOX-M/IVAC), a complete metabolic response occurred.

scholarly journals Improved Detection of Lung or Bone Metastases with an I-131 Whole Body Scan on the 7th Day After High-Dose I-131 Therapy in Patients with Thyroid Cancer

2010 ◽  
Vol 44 (4) ◽  
pp. 273-281 ◽  
Author(s):  
Ari Chong ◽  
Ho-Chun Song ◽  
Jung-Joon Min ◽  
Shin Young Jeong ◽  
Jung-Min Ha ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Bone Metastases ◽  
Whole Body ◽  
High Dose ◽  
Whole Body Scan ◽  
Body Scan
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