Kidney dosimetry in 777 patients during 177Lu-DOTATATE therapy: aspects on extrapolations and measurement time points

Abstract Purpose Fractionated peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE is increasingly applied as an effective treatment for patients with disseminated neuroendocrine tumors. In parallel to dose planning before external beam radiation therapy, dosimetry is also needed to optimize PRRT to the individual patient. Accordingly, absorbed doses to organs at risk need to be calculated during PRRT, based on serial measurements of radioactivity distribution utilizing SPECT/CT. The dosimetry should be based on as few measurements as possible, while still retaining reliable results. The main aim of the present work was to calculate the fractional contribution of the extrapolations of the curve fits for the absorbed dose calculations to the kidneys. The secondary aim was to study agreement between absorbed dose (AD) and the effective half-life (teff) for the kidneys, estimated by means of measurements at one or two time points, in comparison to our current method employing three time points. Methods In 777 patients with disseminated neuroendocrine tumors undergoing PRRT, SPECT/CT over the abdomen was acquired at 1, 4, and 7 days after 177Lu-DOTATATE infusion. The absorbed dose to the kidneys was calculated from SPECT/CT radioactivity distribution data, and the teff and fractional contributions of the extrapolations were estimated, utilizing data from one, two, and three time points, respectively. Results The fractional contributions from extrapolations before day 1 measurement and after day 7 measurement were approximately 26% and 11%, respectively. The mean differences in absorbed dose, based on one, two, and three time points were small, but with high method dependence for individual patients. The differences in estimated teff were small when it was based on measurements at days 1 and 7, but high for days 1 and 4 time points. Conclusion When assessing simplifications of methods for calculation of the absorbed dose to the kidneys, it was of the uttermost importance to incorporate the fractional contribution for the extrapolations included in the reference method. Measurements at an early and a late time point were found most important. An intermediate measurement contributes with an idea of the goodness of the fit.

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EQUIVALENT UNIFORM DOSE SENSITIVITY TO CHANGES IN ABSORBED DOSE DISTRIBUTION

International Journal of Biomathematics ◽

10.1142/s1793524512500696 ◽

2013 ◽

Vol 06 (01) ◽

pp. 1250069

Author(s):

FRANCISCO CUTANDA-HENRÍQUEZ ◽

SILVIA VARGAS-CASTRILLÓN

Keyword(s):

Treatment Planning ◽

Dose Distribution ◽

Absorbed Dose ◽

Target Volume ◽

Simple Expression ◽

External Beam Radiation ◽

Equivalent Uniform Dose ◽

Beam Radiation ◽

Dose Volume Histograms ◽

Small Change

Treatment planning in external beam radiation therapy (EBRT) utilizes dose volume histograms (DVHs) as optimization and evaluation tools. They present the fraction of planning target volume (PTV) receiving more than a given absorbed dose, against the absorbed dose values, and a number of radiobiological indices can be computed with their help. Equivalent uniform dose (EUD) is the absorbed dose that, uniformly imparted, would yield the same biological effect on a tumor as the dose distribution described by the DVH. Uncertainty and missing information can affect the dose distribution, therefore DVHs can be modeled as samples from a set of possible outcomes. This work studies the sensitivity of the EUD index when a small change in absorbed dose distribution takes place. EUD is treated as a functional on the set of DVHs. Defining a Lévy distance on this set and using a suitable expansion of the functional, a very simple expression for a bound on the variation of EUD when the dose distribution changes is found. This bound is easily interpreted in terms of standard treatment planning practice.

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Safety and feasibility of rhenium-186 nanoliposome (186RNL) in recurrent glioma: The ReSPECT phase 1 trial.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.2061 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 2061-2061

Author(s):

Andrew J. Brenner ◽

Ande Bao ◽

William Phillips ◽

Gregory Stein ◽

Vibhudutta Awasthi ◽

...

Keyword(s):

Dose Escalation ◽

Tumor Volume ◽

Phase 1 ◽

Absorbed Dose ◽

External Beam Radiation ◽

Whole Body ◽

Recurrent Glioma ◽

Normal Brain ◽

Beam Radiation ◽

The Mean

2061 Background: While external beam radiation therapy (EBRT) remains a central component of the management of primary brain tumors, it is limited by tolerance of the surrounding normal brain tissue. Rhenium-186 NanoLiposome (186RNL) permits the delivery of beta-emitting radiation of high specific activity with excellent retention in the tumor. We report the results of the phase 1 study in recurrent glioma. Methods: A Phase 1 dose-escalation study of 186RNL in recurrent glioma utilizing a standard 3+3 design was undertaken to determine the maximum tolerated dose of 186RNL. 186RNL is administered by convection enhanced delivery (CED). Infusion is followed under whole body planar imaging and SPECT/CT. Repeat SPECT/CT imaging is performed immediately following, and at 1, 3, 5, and 8 days after 186RNL infusion to obtain dosimetry and distribution. Subjects were followed until disease progression by RANO criteria. Results: Eighteen subjects were treated across 6 cohorts. The mean tumor volume was 9.4 mL (range 1.1 – 23.4). The infused dose ranged from 1.0 mCi to 22.3 mCi and the volume of infusate ranged from 0.66 mL to 8.80 mL. From 1 – 4 CED catheters were used. The maximum catheter flow rate was 15 µl/min. The mean absorbed dose to the tumor volume was 239 Gy (CI 141 – 337; range 9 - 593), to normal brain was 0.72 Gy (CI 0.34 – 1.09; range 0.005 – 2.73), and to total body was 0.07 Gy (CI 0.04 – 0.10; range 0.001 – 0.23). The mean absorbed dose to the tumor volume when the percent tumor volume in the treatment volume was 75% or greater (n = 10) was 392 Gy (CI 306 – 478; range 143 – 593). Scalp discomfort and tenderness related to the surgical procedure did occur in 3 subjects. The therapy has been well tolerated, no dose-limiting toxicity has been observed, and no treatment-related serious adverse events have occurred despite markedly higher absorbed doses typically delivered by EBRT in patients with prior treatment. Responses have been observed supporting the clinical activity. Final results from the dose escalation will be presented. Conclusions: 186RNL administered by CED to patients with recurrent glioma results in a much higher absorbed dose of radiation to the tumor compared to EBRT without significant toxicity. The recommended Phase 2 dose is 22.3 mCi in 8.8 mL of infusate. Clinical trial information: NCT01906385. [Table: see text]

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External Beam Radiation and Brachytherapy for Prostate Cancer: Is It a Possible Trigger of Large Cell Neuroendocrine Carcinoma of the Urinary Bladder?

Case Reports in Oncological Medicine ◽

10.1155/2017/1853985 ◽

2017 ◽

Vol 2017 ◽

pp. 1-4

Author(s):

Ali Zakaria ◽

Bayan Al Share ◽

Sri Kollepara ◽

Cynthia Vakhariya

Keyword(s):

Prostate Cancer ◽

Radiation Therapy ◽

Neuroendocrine Tumors ◽

Neuroendocrine Carcinoma ◽

Large Cell ◽

External Beam Radiation Therapy ◽

Large Cell Neuroendocrine Carcinoma ◽

External Beam Radiation ◽

External Beam ◽

Beam Radiation

Neuroendocrine tumors commonly involve the respiratory and gastrointestinal systems. Primary genitourinary neuroendocrine tumors are rare, accounting for less than 1% of all bladder carcinomas. Four histopathologic subtypes have been described. Among those, large cell neuroendocrine carcinoma (LCNEC) is the least common, is more aggressive, and generally presents in an advanced stage with poor prognosis compared to transitional cell bladder carcinoma. There is no standardized treatment regimen because of the rarity of the disease. Herein, we present a case of 72-year-old male patient with previously treated prostate cancer, who received external beam radiation therapy and high dose brachytherapy, presenting with intermittent hematuria. Cystoscopy and transurethral resection of bladder tumor (TURBT) were performed. The histopathology and immunohistochemistry were consistent with large cell neuroendocrine carcinoma (LCNEC). Further studies are required to proof the higher risk of neuroendocrine carcinoma of the bladder in patients treated with external beam radiation therapy and brachytherapy for prostate cancer.

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Local treatment for focal progression in metastatic neuroendocrine tumors

Endocrine Related Cancer ◽

10.1530/erc-18-0462 ◽

2019 ◽

Vol 26 (4) ◽

pp. 405-409 ◽

Cited By ~ 2

Author(s):

Taymeyah Al-Toubah ◽

Stefano Partelli ◽

Mauro Cives ◽

Valentina Andreasi ◽

Franco Silvestris ◽

...

Keyword(s):

Median Time ◽

Neuroendocrine Tumors ◽

Systemic Treatment ◽

Local Treatment ◽

Arterial Embolization ◽

External Beam Radiation ◽

Gastroenteropancreatic Neuroendocrine Tumors ◽

Beam Radiation ◽

Additional Intervention ◽

Systemic Treatments

New systemic treatments have improved the therapeutic landscape for patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs). While drugs such as everolimus, sunitinib, temozolomide and 177Lutetium-dotatate are appropriate for patients with widespread disease progression, local treatment approaches may be more appropriate for patients with unifocal progression. Surgical resection, radiofrequency ablation (RFA), hepatic arterial embolization (HAE) or radiation, can control discrete sites of progression, allowing patients to continue their existing therapy and sparing them toxicities of a new systemic treatment. We identified 69 patients with metastatic GEP-NETs who underwent a local treatment for focal progression in the setting of widespread metastases. Twenty-six percent underwent resection, 27% RFA, 23% external beam radiation and 23% selective HAE. With a median follow-up of 25 months, 42 (61%) patients subsequently progressed to the point of requiring additional intervention (12 locoregional, 30 systemic) for disease control. Median time to new systemic treatment was 32 months (95% CI, 16.5–47.5 months). Median time to any additional intervention was 19 months (95% CI, 8.7–25.3 months). Control of local sites of progression enabled the majority of patients to remain on their existing systemic treatment and avoid potential toxicities associated with salvage systemic therapy.

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A Probability Approach to the Study on Uncertainty Effects on Gamma Index Evaluations in Radiation Therapy

Computational and Mathematical Methods in Medicine ◽

10.1155/2011/861869 ◽

2011 ◽

Vol 2011 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Francisco Cutanda Henríquez ◽

Silvia Vargas Castrillón

Keyword(s):

Radiation Therapy ◽

Uncertainty Propagation ◽

Absorbed Dose ◽

Planning System ◽

External Beam Radiation ◽

Treatment Planning System ◽

Mathematical Methods ◽

Beam Radiation ◽

Treatment Unit ◽

Gamma Index

Two datasets of points of known spatial positions and an associated absorbed dose value are often compared for quality assurance purposes in External Beam Radiation Therapy (EBRT). Some problems usually arise regarding the pass fail criterion to accept both datasets as close enough for practical purposes. Instances of this kind of comparisons are fluence or dose checks for intensity modulated radiation therapy, modelling of a treatment unit in a treatment planning system, and so forth. The gamma index is a figure of merit that can be obtained from both datasets; it is widely used, as well as other indices, as part of a comparison procedure. However, it is recognized that false negatives may take place (there are acceptable cases where a certain number of points do not pass the test) due in part to computation and experimental uncertainty. This work utilizes mathematical methods to analyse comparisons, so that uncertainty can be taken into account. Therefore, false rejections due to uncertainty do not take place and there is no need to expand tolerances to take uncertainty into account. The methods provided are based on the rules of uncertainty propagation and help obtain rigorous pass/fail criteria, based on experimental information.

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RADT-24. HIGH ABSORBED DOSES OF RHENIUM-186 NANOLIPOSOMES (RNL) IN RECURRENT GBM: A PHASE 1 STUDY

Neuro-Oncology ◽

10.1093/neuonc/noaa215.777 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii186-ii186

Author(s):

Andrew Brenner ◽

John Floyd ◽

Ande Bao ◽

William Phillips ◽

Vibhudutta Awasthi ◽

...

Keyword(s):

Phase 1 ◽

High Specific Activity ◽

Absorbed Dose ◽

External Beam Radiation ◽

Whole Body ◽

Recurrent Glioma ◽

Normal Brain ◽

Beam Radiation ◽

Absorbed Doses ◽

The Mean

Abstract INTRODUCTION While external beam radiation therapy (EBRT) remains a central component of the management of primary brain tumors, it is limited by tolerance of the surrounding normal brain tissue. Nanoliposomal BMEDA-chelated-186Rhenium (RNL™) permits the delivery of beta-emitting radiation of high specific activity with excellent retention in the tumor. We report on the phase 1 results in recurrent glioma. METHODS A phase 1 dose-escalation study of RNL in recurrent glioma utilizing a standard 3 + 3 design was undertaken to determine the maximum tolerated dose of RNL following stereotactic biopsy. RNL is administered with the BrainLab Flexible Catheter by convection enhanced delivery (CED) with placement guided using iPlan Flow and the Varioguide system. Infusion is followed under whole body planar imaging and SPECT/CT. Repeat SPECT/CT imaging is performed immediately following, and at 1, 3, 5, and 8 days after RNL infustion to obtain dosimetry and distribution. RESULTS Thirteen patients have been treated to-date, 12 were recurrent glioblastoma, and 54% failed treatment with bevacizumab. The infused dose was progressively increased from 1.0 mCi to 13.4 mCi and the volume of infusate from 1.0 mL to 5.28 mL using 1 – 2 CED catheters. The mean absorbed dose to the distribution volume was 175 Gy (CI 97 – 254). The maximum absorbed dose to the tumor volume was 593 Gy. The mean retention of the administered dose at 24 hours was 61.4% (CI 45.4 – 77.5). The therapy has been well tolerated and no dose-limiting toxicity has been observed with no treatment related adverse effects despite markedly higher absorbed doses than EBRT in patients with prior treatment. The plan is to increase the dose to 22.3 mCi and the infusate volume to 8.8 mL. CONCLUSION Intratumoral RNL can deliver up to twenty times the absorbed dose of radiation administered by EBRT without significant toxicity.

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