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

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.

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

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]

scholarly journals EPCT-18. A TWO-PART, PHASE 1 STUDY OF RHENIUM-186 NANOLIPOSOME (186RNL) DELIVERED BY CONVECTION ENHANCED DELIVERY FOR RECURRENT, REFRACTORY, OR PROGRESSIVE EPENDYMOMA AND HIGH-GRADE GLIOMA (HGG) AND NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i50-i51
Author(s):  
Ashley Plant ◽  
Stewart Goldman ◽  
Sandi Lam ◽  
Michael DeCuypere ◽  
Gregory Stein ◽  
...  
Keyword(s):  
Specific Activity ◽  
Phase 1 ◽  
High Specific Activity ◽  
External Beam Radiation ◽  
Central Component ◽  
Normal Brain ◽  
Newly Diagnosed ◽  
Convection Enhanced Delivery ◽  
Beam Radiation ◽  
Dose Limiting Toxicity

Abstract Ependymoma, HGG, and DIPG are gliomas that are often difficult to treat, frequently aggressive, and often carry an extremely poor prognosis. While external beam radiation therapy (EBRT) remains a central component of the management of pediatric gliomas, it is limited by tolerance of the surrounding normal brain tissue. Rhenium-186 NanoLiposome (186RNL) permits the selective delivery of beta-emitting radiation of high specific activity with excellent retention in the tumor. In a Phase 1 trial in adults with recurrent glioblastoma (NCT01906385), the mean absorbed dose to the tumor when coverage was 75% or greater (n=10) was 392 Gy (CI 306 – 478). Thus far, 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 than typically delivered by EBRT (n=18). Methods This is a two-part, Phase 1 dose-finding study followed by an expansion cohort to explore efficacy. Part 1 will enroll up to 18 subjects to determine the maximum feasible dose (MFD) of 186RNL administered by convection enhanced delivery (CED). Tumor size will be limited to a diameter of 4 cm in the longest axis and a volume of 34 mL. The dose limiting toxicity period (DLT) is 28 days post infusion. Part 2 will independently evaluate 186RNL in 3 different cohorts: Cohort A: up to 12 subjects with a diagnosis of recurrent, refractory, or progressive ependymoma; Cohort B: up to 12 subjects with a diagnosis of recurrent, refractory, or progressive HGG; Cohort C: up to 15 subjects with newly diagnosed DIPG. The primary endpoint is overall response rate (ORR) by Radiographic Assessment in Pediatric Neuro-Oncology (RAPNO) criteria. Secondary endpoints are PFS-24 and OS-24 in Cohort A and PFS-12 and OS-12 in Cohorts B and C. Planned enrollment will begin in H2 2021.

Phase 1 trial study of 131I-labeled chimeric 81C6 monoclonal antibody for the treatment of patients with non-Hodgkin lymphoma

Blood ◽  
2004 ◽  
Vol 104 (3) ◽  
pp. 642-648 ◽  
Author(s):  
David A. Rizzieri ◽  
Gamal Akabani ◽  
Michael R. Zalutsky ◽  
R. Edward Coleman ◽  
Scott D. Metzler ◽  
...  
Keyword(s):  
Stem Cell ◽  
Phase 1 ◽  
Absorbed Dose ◽  
Whole Body ◽  
Hematologic Toxicity ◽  
Blocking Antibody ◽  
Non Hodgkin Lymphoma ◽  
Body Activity ◽  
The Mean ◽  
Administered Activity

AbstractWe report a phase 1 study of pharmacokinetics, dosimetry, toxicity, and response of 131I anti-tenascin chimeric 81C6 for the treatment of lymphoma. Nine patients received a dosimetric dose of 370 MBq (10 mCi). Three patients received an administered activity of 1480 MBq (40 mCi), and 2 developed hematologic toxicity that required stem cell infusion. Six patients received an administered activity of 1110 MBq (30 mCi), and 2 developed toxicity that required stem cell infusion. The clearance of whole-body activity was monoexponential with a mean effective half-life of 110 hours (range, 90-136 hours) and a mean effective whole-body residence time of 159 hours (range, 130-196 hours). There was rapid uptake within the viscera; however, tumor uptake was slower. Activity in normal viscera decreased proportional to the whole body; however, tumor sites presented a slow clearance (T1/2, 86-191 hours). The mean absorbed dose to whole-body was 67 cGy (range, 51-89 hours), whereas the dose to tumor sites was 963 cGy (range, 363-1517 cGy). Despite lack of a “blocking” antibody, 1 of 9 patients attained a complete remission and 1 a partial remission. These data demonstrate this radiopharmaceutical to be an encouraging agent for the treatment of lymphoma particularly if methods to protect the normal viscera are developed.

A Simple Method for the Evaluation of Internal Doses in Nuclear Medicine

1974 ◽  
Vol 13 (02) ◽  
pp. 193-206
Author(s):  
L. Conte ◽  
L. Mombelli ◽  
A. Vanoli
Keyword(s):  
Nuclear Medicine ◽  
Close Agreement ◽  
Whole Body ◽  
Simple Method ◽  
Rapid Estimation ◽  
Absorbed Doses ◽  
The Mean ◽  
The Individual ◽  
Estimation Of Risk

SummaryWe have put forward a method to be used in the field of nuclear medicine, for calculating internally absorbed doses in patients. The simplicity and flexibility of this method allow one to make a rapid estimation of risk both to the individual and to the population. In order to calculate the absorbed doses we based our procedure on the concept of the mean absorbed fraction, taking into account anatomical and functional variability which is highly important in the calculation of internal doses in children. With this aim in mind we prepared tables which take into consideration anatomical differences and which permit the calculation of the mean absorbed doses in the whole body, in the organs accumulating radioactivity, in the gonads and in the marrow; all this for those radionuclides most widely used in nuclear medicine. By comparing our results with dose obtained from the use of M.I.R.D.'s method it can be seen that when the errors inherent in these types of calculation are taken into account, the results of both methods are in close agreement.

EQUIVALENT UNIFORM DOSE SENSITIVITY TO CHANGES IN ABSORBED DOSE DISTRIBUTION

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.

scholarly journals Is nuclear medicine really safe?

2002 ◽  
Vol 45 (spe) ◽  
pp. 115-118
Author(s):  
Nicole Colas-Linhart
Keyword(s):  
Nuclear Medicine ◽  
Human Serum Albumin ◽  
Radiation Dose ◽  
Serum Albumin ◽  
Human Serum ◽  
Absorbed Dose ◽  
Cellular Level ◽  
Whole Body ◽  
Absorbed Doses ◽  
Standard Models

In nuclear medicine, radiation absorbed dose estimates calculated by standard models at the whole body or organ are very low. At cellular level, however, the heterogeneity of radionuclide distributions of radiation dose patterns may be significant. We present here absorbed doses at cellular level and evaluate their possible impact on the usually assumed risk/benefit relationships in nuclear medicine studies. The absorbed dose values calculated are surprisingly high, and are difficult to interpret. In the present study, we show calculated doses at the cellular level and discuss possible biological consequences, for two radiopharmaceuticals labelled with technetium-99m: human serum albumin microspheres used for pulmonary scintigrapies and HMPAO used to labelled leukocytes.

scholarly journals Is it necessary to reduce the radioiodine dose in patients with thyroid cancer and renal failure?

2010 ◽  
Vol 54 (4) ◽  
pp. 413-418 ◽  
Author(s):  
José Willegaignon ◽  
Verena Pinto Brito Ribeiro ◽  
Marcelo Sapienza ◽  
Carla Ono ◽  
Tomoco Watanabe ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Dose Adjustment ◽  
Absorbed Dose ◽  
Whole Body ◽  
Half Time ◽  
Dialysis Therapy ◽  
Absorbed Doses ◽  
131I Activity ◽  
Dosimetric Data ◽  
Higher Doses

The objective of this study were to obtain dosimetric data from a patient with thyroid cancer simultaneously undergoing peritoneal dialysis therapy, so as to determine the appropriate amount of 131I activity to be applied therapeutically. Percentages of radioiodine in the blood and the whole-body were evaluated, and radiation absorbed doses were calculated according to OLINDA/EXM software. Whole-body 131I effective half-time was 45.5 hours, being four times longer than for patients without any renal dysfunction. Bone-marrow absorbed dose was 0.074 mGy/MBq, with ablative procedure maintenance at 3.7 GBq, as the reported absorbed dose was insufficiently restrictive to change the usual amount of radioiodine activity administered for ablation. It was concluded that radioiodine therapeutic-dose adjustment, based on individual patient dosimetry, is an important way of controlling therapy. It also permits the safe and potential delivery of higher doses of radiation to tumors and undesirable tissues, with a minimum of malignant effects on healthy tissues.

scholarly journals A prospective study on pain score with transperineal prostatic gold seed fiducial implantation under local anesthetic alone

2013 ◽  
Vol 7 (3-4) ◽  
pp. e202-6 ◽  
Author(s):  
Colin I. Tang ◽  
Perakaa Sethukavalan ◽  
Patrick Cheung ◽  
Gerard Morton ◽  
Geordi Pang ◽  
...  
Keyword(s):  
Pain Score ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
Seed Implantation ◽  
Pain Scores ◽  
Patient Pain ◽  
Procedural Complications ◽  
Gold Seed ◽  
The Mean ◽  
A Prospective Study

Background: The purpose of this study was to monitor patient pain score with transperineal prostatic gold seed implantation in the absence of conscious sedation.Methods: All patients who were scheduled for image-guided external beam radiation (IGRT) and referred for gold seed fiducials were eligible to participate. Gold seed implants were performed by two radiation oncologists between December 2007 and April 2008. Patients received only local and deep anesthetic. No patients had prophylactic IV cannulation for the procedure. Three gold seeds were inserted transperineally into the prostate. A visual analogue scale from 0 to 10 was used to assess the pain at baseline, local and deep anesthetic infiltration, with each seed drop, and after the completion of the procedure.Results: A total of 30 patients were accrued to this study. The highest recorded increase in pain score was at the time point of deep local anesthesia, at which the mean pain score was 3.8. The mean pain scores at each seed drop were 0.8 (standard deviation [SD]=1.24), 1 (SD=1.26), and 0.5 (SD=0.90), respectively. All gold seed insertion procedures were well-tolerated, with no patient shaving significant pain post-procedure, and no significant procedural complications. There were only slight increases in dysuria, urinary frequency, constipation, urinary retention and flatulence in 7 patients – none of which required intervention.Interpretation: Transperineal ultrasound-guided gold seed implantation without conscious sedation is well-tolerated and associated with a low complication rate. It is a convenient outpatient procedure obviating the need for resource intensive postoperative monitoring.

Hemangiopericytoma: long-term outcome revisited

2011 ◽  
Vol 114 (3) ◽  
pp. 747-755 ◽  
Author(s):  
Marco Schiariti ◽  
Pablo Goetz ◽  
Hussien El-Maghraby ◽  
Jignesh Tailor ◽  
Neil Kitchen
Keyword(s):  
Overall Survival ◽  
Local Recurrence ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
Long Term Outcome ◽  
Free Interval ◽  
Initial Surgery ◽  
The Mean

Object Hemangiopericytomas are rare tumors that behave aggressively with a high rate of local recurrence and distant metastases. With the aim of determining the outcome and response to various treatment modalities, a series of 39 patients who underwent microsurgical resection for primary meningeal hemangiopericytoma over a 24-year period is presented. Methods Patients with hemangiopericytoma were identified from histopathology records and their medical records were analyzed retrospectively by 2 independent reviewers to collect data on surgical treatment, adjuvant therapy, postoperative course, local or distant recurrence, and follow-up. Results Of the 39 patients, 19 were male and 20 were female. Mean patient age was 44.1 years. Thirty-four tumors were intracranial and 5 were spinal. The mean follow-up period was 123 months. Twenty-eight patients developed local recurrence. The recurrence rate at 1, 5, and 15 years was 3.5%, 46%, and 92%, respectively. Extraneural metastasis occurred in 8 patients (26%) at an average of 123 months after initial surgery. Recurrences and metastases were treated by surgical excision, external beam radiation therapy (EBRT), chemotherapy, and/or stereotactic radiosurgery. Adjuvant EBRT following initial surgery was found to extend the disease-free interval from 154 months to 254 months, although it did not prevent the development of metastasis. In those patients with EBRT and complete resection, the mean recurrence-free interval was found to be 126.3 months longer (p = 0.04) and overall survival 126 months longer than without EBRT. Furthermore, adjusting for resection, patients undergoing EBRT had 0.33 times increased risk of recurrence compared with those who did not (p = 0.03). A majority of patients remained able to live independently despite revision surgery for recurrence. Conclusions The mean follow-up of this patient series represents the longest follow-up duration published to date and demonstrates extended survival in a significant number of patients with hemangiopericytoma. Gross-total resection followed by adjuvant EBRT provides patients with the highest probability of an increased recurrence-free interval and overall survival. Prolonged survival justifies long-term follow-up and aggressive treatment of initial, recurrent, and metastatic disease.

scholarly journals SUN-LB77 Incidental Anaplastic Thyroid Carcinoma: An Uncommon Entity

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Preethi Padmanaban ◽  
Eric Nylen
Keyword(s):  
Thyroid Cancer ◽  
Adjuvant Therapy ◽  
Median Survival ◽  
Anaplastic Thyroid Cancer ◽  
Anaplastic Carcinoma ◽  
External Beam Radiation ◽  
Whole Body ◽  
American Thyroid Association ◽  
Beam Radiation ◽  
Disease Free

Abstract Background: Anaplastic thyroid cancer is an aggressive thyroid malignancy with a median survival of 3 to 9 months. It is rare and represents 2-5% of all thyroid tumors. Even more uncommonly in about 2%–6% of all ATC cases, it is identified as a small, incidental finding after surgical resection of a predominantly non-anaplastic tumor. Clinical Case: We report a case of 67 year old Caucasian male who presented with history of hoarseness of voice for one month. Fine needle aspiration biopsy of right dominant thyroid nodule revealed papillary thyroid cancer. Pre-operative imaging was negative for involvement of surrounding structures or distant metastasis. He underwent total thyroidectomy and final pathology revealed Anaplastic carcinoma arising in papillary carcinoma measuring 3.6cm in greatest dimension. Undifferentiated (Anaplastic) Carcinoma comprised approximately 5% of the tumor. Areas from anaplastic and papillary tumor were dissected separately. DNA separated from these two specimens were analyzed by PCR amplification and both were positive for BRAF mutation. External beam radiation and radioactive iodine therapy were administered after surgery. Given absence of invasion or metastasis adjuvant therapy was not initiated. His positron emission tomography, computed tomography imaging and whole-body scan has been negative for residual/ recurrent or metastatic disease. He remains disease free at 18 months after diagnosis. Discussion: Anaplastic thyroid cancer is a rare but highly aggressive tumor. In most cases it develops from a pre-existing well differentiated thyroid cancer. ATC incidence typically peaks at the 6-7th decade of life, predominantly in women. The median survival is between 3 to 9 months with less than 10% of patients alive 3 years after the time of diagnosis. Because of its aggressive behavior, the American Joint Committee on Cancer Staging Manual classifies all Anaplastic thyroid cancer Stage IV tumors. Surgery, chemotherapy and radiotherapy are the conventional therapeutic strategies performed in the attempt to improve survival. However, incidental anaplastic thyroid cancer is rare variant with very few reported cases. American Thyroid Association (ATA) Guidelines for Management of Patients with ATC do not include specific recommendations for this form of ATC. There is no consensus to define best treatment approach as to whether intrathyroidal incidentally detected ATC is best treated with surgery alone, surgery followed by radiotherapy, or surgery followed by chemotherapy plus radiation therapy. Conclusion: Based on review of our case as well as outcomes of similar reported cases, prognosis is favorable for incidental anaplastic thyroid cancer. Hopefully, with more data from similar cases to demonstrate difference in disease free survival we should be able to define the role of chemotherapy and adjuvant therapy for incidental ATC better. The question remains open, as to whether incidental anaplastic thyroid cancer should be considered as a separate entity from aggressive form of ATC.

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