Haematopoietic toxicity of radium-223 in patients with high skeletal tumour burden

Miederer, Matthias; Thomas, C.; Beck, J. D.; Hampel, C.; Krieger, Christine C; Baqué, P. E.; Helisch, Andreas; Schreckenberger, Mathias

doi:10.3413/nukmed-0751-15-06

Cited by 18 publications

(16 citation statements)

References 9 publications

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“…Dose-limiting toxicities, however, are usually well described. For [ 225 Ac]Ac-PSMA-617, for instance, the destruction of the salivary glands represents the dose-limiting organ [34], whereas for [ 223 Ra]RaCl 2 haematotoxicity can lead to premature termination of the therapy [113]. Furthermore, the high LET radiation might lead to cancer induction and genetic diseases [112,114,115].…”

Section: Atomic Nanogenerators In Modern Cancer Managementmentioning

confidence: 99%

Atomic Nanogenerators in Targeted Alpha Therapies: Curie’s Legacy in Modern Cancer Management

2020

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Atomic in vivo nanogenerators such as actinium-225, thorium-227, and radium-223 are of increasing interest and importance in the treatment of patients with metastatic cancer diseases. This is due to their peculiar physical, chemical, and biological characteristics, leading to astonishing responses in otherwise resistant patients. Nevertheless, there are still a few obstacles and hurdles to be overcome that hamper the broader utilization in the clinical setting. Next to the limited supply and relatively high costs, the in vivo complex stability and the fate of the recoiling daughter radionuclides are substantial problems that need to be solved. In radiobiology, the mechanisms underlying treatment efficiency, possible resistance mechanisms, and late side effect occurrence are still far from being understood and need to be unraveled. In this review, the current knowledge on the scientific and clinical background of targeted alpha therapies is summarized. Furthermore, open issues and novel approaches with a focus on the future perspective are discussed. Once these are unraveled, targeted alpha therapies with atomic in vivo nanogenerators can be tailored to suit the needs of each patient when applying careful risk stratification and combination therapies. They have the potential to become one of the major treatment pillars in modern cancer management.

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Section: Atomic Nanogenerators In Modern Cancer Managementmentioning

confidence: 99%

Atomic Nanogenerators in Targeted Alpha Therapies: Curie’s Legacy in Modern Cancer Management

2020

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“…Most single-institution studies (n = 9/25, 36%) originated from the United States; moreover, most of the multi-institutional studies included an American center (n = 6/9, 67%) [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Five studies originated from Germany [ 23 , 24 , 25 , 26 , 27 ], four from Sweden [ 28 , 29 , 30 , 31 ], and six from Japan [ 32 , 33 , 34 , 35 , 36 , 37 ]. Information about patient number, acquisition technique, type of employed isotope (when applicable) and method of computational analysis were obtainable from all studies.…”

Section: Resultsmentioning

confidence: 99%

Assessment of Skeletal Tumor Load in Metastasized Castration-Resistant Prostate Cancer Patients: A Review of Available Methods and an Overview on Future Perspectives

et al. 2018

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Metastasized castration-resistant prostate cancer (mCRPC), is the most advanced form of prostate neoplasia, where massive spread to the skeletal tissue is frequent. Patients with this condition are benefiting from an increasing number of treatment options. However, assessing tumor response in patients with multiple localizations might be challenging. For this reason, many computational approaches have been developed in the last decades to quantify the skeletal tumor burden and treatment response. In this review, we analyzed the progressive development and diffusion of such approaches. A computerized literature search of the PubMed/Medline was conducted, including articles between January 2008 and March 2018. The search was expanded by manually reviewing the reference list of the chosen articles. Thirty-five studies were identified. The number of eligible studies greatly increased over time. Studies could be categorized in the following categories: automated analysis of 2D scans, SUV-based thresholding, hybrid CT- and SUV-based thresholding, and MRI-based thresholding. All methods are discussed in detail. Automated analysis of bone tumor burden in mCRPC is a growing field of research; when choosing the appropriate method of analysis, it is important to consider the possible advantages as well as the limitations thoroughly.

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“…In contrast to the ALSYMPCA trial, in which the bone scan response to treatment with 223 Ra was not evaluated, there are some studies that have focused on the utility of bone scans (scintigraphy and PET) to assess the response and toxicity associated with this therapy (36)(37)(38). In recent years, PSMA PET/CT has been making ground-breaking changes in the diagnosis and staging of PC patients, and this imaging modality is superior to choline PET (16,18,39,40).…”

Section: Discussionmentioning

confidence: 99%

“…Changes in the ALP value are often used as a marker for treatment follow-up, because ALP may reflect the extent of bone disease more accurately than PSA levels (38). In the ALSYMPCA trial, a significantly higher proportion of patients showed a response according to the ALP level in the 223 Ra group than in the placebo group ($30% reduction, P , 0.001).…”

Section: Discussionmentioning

confidence: 99%

⁶⁸Ga-PSMA-11 PET as a Gatekeeper for the Treatment of Metastatic Prostate Cancer with ²²³Ra: Proof of Concept

et al. 2016

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We retrospectively evaluated the utility of 68 Ga-PSMA-11 PET for planning 223 RaCl 2 therapy of patients with metastatic prostate cancer and its impact on the therapeutic response as determined by prostatespecific antigen (PSA) and alkaline phosphatase (ALP), as well as the correlation of PSA changes with the results of prostate-specific membrane antigen (PSMA) PET follow-up scans. Methods: Sixtythree patients with a median age of 73 y who underwent 307 cycles of therapy with 223 RaCl 2 were analyzed. In 31 patients, bone scanning and radiologic imaging were performed for pretherapeutic imaging (group 1). In 32 patients, bone scanning and PSMA PET were performed before therapy (group 2). Patients with small lymph node metastases and local recurrence were not excluded from treatment, consistent with current guidelines. PSA and ALP were measured before each treatment cycle and 4 wk after the final cycle. Thirteen patients from group 2, who underwent a second PSMA PET scan as a followup, were evaluated to determine the significance of PSA changes as a follow-up marker. Results: In group 1, 4 patients (12.9%) showed a PSA decline, of whom 2 patients and 1 patient showed a PSA decline of more than 30% and more than 50%, respectively. In contrast, in group 2, 14 patients (43.8%) showed a PSA decline, of whom 10 and 8 patients showed a decline of more than 30% and more than 50%, respectively (P 5 0.007). Thirty-seven patients had a high ALP level (19 from group 1 and 18 from group 2). Twelve (63.2%) and 16 (88.9%) patients in groups 1 and 2, respectively, showed an ALP decline. This difference was not significant; however, 7 (36%) and 13 (72.2%) patients in groups 1 and 2, respectively, showed an ALP decline of more than 30% (P 5 0.04). Considering any ALP decline as a response, no patient with increasing ALP showed a PSA response (P 5 0.036). There was a significant correlation between the PSA changes and the therapeutic response according to follow-up PSMA PET. Conclusion: When PSMA PET is used as the gatekeeper in addition to bone scanning, radionuclide therapy with 223 Ra may be more effective and have more success regarding changes in the PSA. An increase in PSA during therapy cycles occurs because of disease progression.

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Haematopoietic toxicity of radium-223 in patients with high skeletal tumour burden

Abstract: Close follow-up of haematopoietic indices and, in case of toxicity, early termination of therapy is in particular necessary in late stage disease where limited bone marrow reserve is likely.

Cited by 18 publications

References 9 publications

Atomic Nanogenerators in Targeted Alpha Therapies: Curie’s Legacy in Modern Cancer Management

Atomic Nanogenerators in Targeted Alpha Therapies: Curie’s Legacy in Modern Cancer Management

Assessment of Skeletal Tumor Load in Metastasized Castration-Resistant Prostate Cancer Patients: A Review of Available Methods and an Overview on Future Perspectives

⁶⁸Ga-PSMA-11 PET as a Gatekeeper for the Treatment of Metastatic Prostate Cancer with ²²³Ra: Proof of Concept

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Haematopoietic toxicity of radium-223 in patients with high skeletal tumour burden

Abstract: Close follow-up of haematopoietic indices and, in case of toxicity, early termination of therapy is in particular necessary in late stage disease where limited bone marrow reserve is likely.

Cited by 18 publications

References 9 publications

Atomic Nanogenerators in Targeted Alpha Therapies: Curie’s Legacy in Modern Cancer Management

Atomic Nanogenerators in Targeted Alpha Therapies: Curie’s Legacy in Modern Cancer Management

Assessment of Skeletal Tumor Load in Metastasized Castration-Resistant Prostate Cancer Patients: A Review of Available Methods and an Overview on Future Perspectives

68Ga-PSMA-11 PET as a Gatekeeper for the Treatment of Metastatic Prostate Cancer with 223Ra: Proof of Concept

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⁶⁸Ga-PSMA-11 PET as a Gatekeeper for the Treatment of Metastatic Prostate Cancer with ²²³Ra: Proof of Concept