RADT-08. A VOLUMETRIC ANALYSIS OF STEREOTACTIC RADIOSURGERY LOW DOSE VOLUMES IN PREVENTING FUTURE BRAIN METASTASES

Abstract PURPOSE/OBJECTIVE(S) Stereotactic radiosurgery (SRS), compared to whole brain radiotherapy is limited in its ability to prevent development of brain metastases in untreated areas. The purpose of this study is to assess whether low-dose volumes delivered to uninvolved regions of the brain during SRS can reduce the risk of developing brain metastases in those regions. MATERIALS AND METHODS Data were collected for 69 patients with brain metastases who were treated with SRS at least two occasions. The regions of uninvolved brain receiving a high, intermediate, and low dose of incidental radiotherapy were defined as the volume receiving at least 10, 5, and 2.5 Gy if the prescribed dose was < 25 Gy (1-3 fraction plans) or the volume receiving at least 15, 7.5, and 5 Gy if the prescribed dose was ≥ 25 Gy (5 fraction plans). A second round metastasis was considered to occur within a given dose level if 20% or more of the tumor was found within that dose level. Probabilities were calculated based on the volume of each dose level as a percentage of total brain volume and were used to estimate the expected number of cases with at least one metastasis occurring in each dose level. RESULTS The average number of metastases treated in both rounds of SRS was two. The expected and observed number of cases with at least one second round metastasis were 0 and 2 for the high dose level (p=0.151), 7 and 3 for the intermediate dose level (p=0.018), and 17 and 11 for the low dose level (p=0.094). CONCLUSION We observed fewer than expected new metastases within prior SRS low dose levels based on volumetric probabilities, though this difference was only significant for the intermediate dose level. This suggests that low dose volumes from SRS may provide benefit in preventing future regional metastases.

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Experimental autoimmune encephalomyelitis inhibited by Huangqi Guizhi Wuwu Decoction by enhancing Th2 cytokine

10.21203/rs.3.rs-29688/v1 ◽

2020 ◽

Author(s):

Yong Peng ◽

Fei-Zhou Zhu ◽

Jian-Xiong Zhou ◽

Shuai Gao ◽

Zhi-Xing Chen ◽

...

Keyword(s):

T Cells ◽

Dose Level ◽

Low Dose ◽

Conventional Medicine ◽

High Dose ◽

Distilled Water ◽

Autoimmune Encephalomyelitis ◽

High Dose Level ◽

Th2 Cytokine ◽

Proliferation Assays

Abstract Background: Current modern conventional medicine (MCM) on multiple sclerosis (MS) are non-specific immunosuppressive drugs, which remains many side effects. Huangqi Guizhi Wuwu decoction (HQGZWW) is a common formula of Chinese herbal medicine (CHM) has good effects on treatment of MS and its animal model, experimental autoimmune encephalomyelitis (EAE) very well, so it is very important to understand the precise mechanism. Our previous study suggested that CD8+ autoreactive T cells in EAE had a lower encephalitogenic function but were unique and independent on pathogenic of EAE rather than their CD4+ counterparts. The aims of current study were to determine the pathological interrelationship between CD4+ and CD8+ autoreactive T cells in MS/EAE upon the HQGZWW treatment.Methods: Female C57BL/6 mice (n=8, each group) were induced by myelin oligodendrocyte glycoprotein (MOG)35-55 peptide, and meantimely were treated with distilled water, prednisone, high dose or low dose HQGZWW. At 14 days after immunization, T cells were isolated from the spleen and purified as CD4+ and CD8+ T cells by using CD4 and CD8 isolation kits, and then the purity was determined by flow cytometric analysis. These cells were stimulated by MOG35-55 peptide and applied to proliferation assays. The interferon-gamma (IFN-g), interleukin (IL)-4 and IL-10 secretion of supernatant of cultured CD4+ and CD8+ T cells were measured by enzyme-linked immunosorbent assays (ELISA). For adoptive transfer, recipient mice were injected with MOG35-55 -specific CD8+ or CD4+ T cells. EAE clinical course was measured by EAE score at 0-5 scale and spinal cord was examined by staining with hematoxylin and eosin and Luxol fast blue staining.Results: For aEAE, there were significant improvement of EAE score in both HQGZWW high dose and prednisone groups by EAE score and pathological examination of spinal cord. CD8+ CD3+ and CD4+CD3+ cells were around 90% pure of total CD3+ cells after CD8/CD4 bead enrichment in 4 groups, respectively. These cells were stimulated by MOG35–55 peptide and applied to proliferation assays. There is lower antigen-specific responses of CD8+ as well as CD4+ T cells in HQGZWW high dose and prednisone group, compared with HQGZWW low dose and distilled water groups. For cytokine profiles, the CD4+ and CD8+ T cell supernatants contained lower levels of IFN-g and higher levels of IL-4 and IL-10 in HQGZWW high dose and prednisone groups compared with HQGZWW low dose and distilled water groups. Finally, HQGZWW had similar effect at high dose level to typical conventional medicine prednisone on tEAE, but no effect at low dose level.Conclusion: Our data suggested that HQGZWW had similar effect at high dose level to typical conventional medicine prednisone on EAE, but no effect at low dose level, and it suggested that the protection role of HQGZWW on EAE might be upon Th2 cytokine secretion profile by either MOG35–55 specific CD8+ or CD4+ T cells.

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A Volumetric Analysis of Stereotactic Radiosurgery Low Dose Volumes in Preventing Future Brain Metastases

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2020.07.2064 ◽

2020 ◽

Vol 108 (3) ◽

pp. e695

Author(s):

J.W. Shumway ◽

W.S. Yoon ◽

X. Tan ◽

E.C. Schreiber ◽

T. Yanagihara ◽

...

Keyword(s):

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Low Dose ◽

Volumetric Analysis ◽

Dose Volumes

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Effects of α-adrenoceptor agonists and antagonists on thyroid hormone secretion

Acta Endocrinologica ◽

10.1530/acta.0.1080184 ◽

1985 ◽

Vol 108 (2) ◽

pp. 184-191 ◽

Cited By ~ 13

Author(s):

Bo Ahrén

Keyword(s):

Thyroid Hormone ◽

Dose Level ◽

Hormone Secretion ◽

High Dose ◽

Inhibitory Effects ◽

High Dose Level ◽

Adrenoceptor Antagonist ◽

Adrenoceptor Agonist ◽

Adrenoceptor Agonists

Abstract. The effects of various α-adrenoceptor agonists and antagonists on blood radioiodine levels were studied in mice pre-treated with 125I and thyroxine. The non-selective α-adrenoceptor agonist noradrenaline and the selective α1-adrenoceptor agonist phenylephrine both enhanced blood radioiodine levels. Noradrenaline was more potent than phenylephrine. Contrary, the selective α2-adrenoceptor agonist clonidine depressed basal levels of blood radioiodine. The non-selective α-adrenoceptor antagonist phentolamine and the selective α1-adrenoceptor antagonist prazosin both inhibited the noradrenaline-induced elevation of radioiodine levels, whereas the α2-adrenoceptor antagonist yohimbine had no such effect, except at a high dose level. All three α-adrenoceptor agonists, noradrenaline, phenylephrine and clonidine, inhibited the radioiodine response to TSH. In addition, TSH-induced increase in radioiodine levels was inhibited by prazosin, whereas yohimbine had no effect. Phentolamine inhibited the radioiodine response to TSH when given 2 h prior to TSH, whereas when given 15 min prior to TSH the response to TSH was potentiated by Phentolamine. It is concluded, that under in vivo conditions in the mouse, α1-adrenoceptor activation stimulates basal thyroid hormone secretion and inhibits TSH-induced thyroid hormone secretion. Further, α2-adrenoceptor activation inhibits basal thyroid hormone secretion. In addition, TSH-induced thyroid hormone secretion is inhibited by α1-adrenoceptor antagonism. Thus, α-adrenoceptors induce both stimulatory and inhibitory effects of thyroid function.

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CTNI-28. VOLUMETRIC AND DOSIMETRIC PATTERNS OF FAILURE ANALYSIS OF A PHASE II CLINICAL TRIAL OF 18F-DOPA-PET DIRECTED DOSE ESCALATED RADIOTHERAPY FOR GLIOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noab196.253 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi65-vi65

Author(s):

William Breen ◽

S Keith Anderson ◽

Deanna Pafundi ◽

Timothy Kaufmann ◽

Christopher Hunt ◽

...

Keyword(s):

Clinical Trial ◽

Phase Ii ◽

Low Dose ◽

Recursive Partitioning ◽

Secondary Analysis ◽

Progression Free Survival ◽

Phase Ii Clinical Trial ◽

High Dose ◽

Patterns Of Failure ◽

Dose Volumes

Abstract While dose escalation of radiotherapy (DERT) has failed to improve overall survival (OS) or progression-free survival (PFS) for glioblastoma in previous studies, a recent phase II clinical trial utilizing 18F-DOPA-PET-directed DERT demonstrated improved PFS in MGMT-unmethylated patients and OS in MGMT-methylated patients compared to historical controls. This planned secondary analysis sought to determine 1) how 18F-DOPA-PET changes RT volumes beyond standard MRI-planning, 2) which patients benefit most and least from this protocol, 3) which are mostly likely to experience clinically significant radionecrosis after DERT, and 4) patterns of failure after DERT. For 69 evaluable patients, median MRI-defined, PET-defined, and combined low-dose gross tumor volumes (GTV51) were 54 cc (range 9-248), 23 cc (0.4-179), and 62 cc (10-260), respectively. Median MRI-defined, PET-defined, and combined high-dose GTVs (GTV76) were 32 cc (range 4-136), 6 cc (0.1-138), and 34 cc (4-162), respectively. 18F-DOPA-PET resulted in a median volumetric expansion of 13% (0-243%) and 5% (0-217%) from MRI-defined low-dose and high-dose GTV’s, respectively. Central failures ( >95% of recurrence tumor volume) occurred within the 76 Gy, 60 Gy, and 51 Gy isodose lines in 32 (46%), 60 (87%), and 64 (93%) patients, respectively. Recursive partitioning analysis stratified patients by OS and PFS. Patients with 18F-DOPA-PET-defined GTV76 > 7.8cc, MRI-defined GTV76 > 42.7cc, and MGMT promotor-unmethylated tumors had the shortest OS, while patients with smaller PET and MRI-defined tumors had the longest OS (median 10.4 vs. 64.6 months, p< 0.001). Similarly, PFS was worst in patients with 18F-DOPA-PET-defined GTV76 > 2.17 cc who had biopsy only (median PFS 3.2 months, p< 0.001). Patients with 18F-DOPA-PET-defined GTV51 > 50 cc had the highest risk of grade 3+ radionecrosis (p< 0.001). In conclusion, larger 18F-DOPA-PET and MRI-defined tumor volumes were associated with worse outcomes, and 18F-DOPA-PET-directed DERT appears to reduce risk of central recurrence in high-dose volumes.

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Treatment planning for MLC based robotic radiosurgery for brain metastases: plan comparison with circular fields and suggestions for planning strategies

Current Directions in Biomedical Engineering ◽

10.1515/cdbme-2017-0032 ◽

2017 ◽

Vol 3 (2) ◽

pp. 151-154

Author(s):

Daniela Schmitt ◽

Rami El Shafie ◽

Sebastian Klüter ◽

Nathalie Arians ◽

Kai Schubert ◽

...

Keyword(s):

Brain Metastases ◽

Low Dose ◽

Treatment Time ◽

Conformity Index ◽

High Dose ◽

Gradient Index ◽

Plan Comparison ◽

Robotic Radiosurgery ◽

Target Volumes ◽

Beam Transmission

AbstractTo evaluate the possible range of application of the new InCise2 MLC for the CyberKnife M6 system in brain radiosurgery, a plan comparison was made for 10 brain metastases sized between 1.5 and 9cm3 in 10 patients treated in a single fraction each. The target volumes consist of a PTV derived by expanding the GTV by 1mm and were chosen to have diversity in the cohort regarding regularity of shape, location and the structures needed to be blocked for beam transmission in the vicinity. For each case, two treatment plans were optimized: one using the MLC and one using the IRIS-collimator providing variable circular fields. Plan re-quirements were: dose prescription to the 70% isodose line (18 or 20Gy), 100% GTV coverage, ≥98% PTV coverage, undisturbed central high dose region (95% of maximum dose) and a conformity index as low as possible. Plan com-parison parameters were: conformity index (CI), high-dose gradient index (GIH), low-dose gradient index (GIL), total number of monitor units (MU) and expected treatment time (TT). For all cases, clinically acceptable plans could be gen-erated with the following results (mean±SD) for CI, GIH, GIL, MU and TT, respectively for the MLC plans: 1.09±0.03, 2.77±0.26, 2.61±0.08, 4514±830MU and 27±5min and for the IRIS plans: 1.05±0.01, 3.00±0.35, 2.46±0.08, 8557±1335MU and 42±7min. In summary, the MLC plans were on average less conformal and had a shallower dose gradient in the low dose region, but a steeper dose gradient in the high dose region. This is accompanied by a smaller vol-ume receiving 10Gy. A plan by plan comparison shows that usage of the MLC can spare about one half of the MUs and one third of treatment time. From these experiences and results suggestions for MLC planning strategy can be de-duced.

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Effects of replacement therapies with clotting factors in patients with hemophilia: A systematic review and meta-analysis

PLoS ONE ◽

10.1371/journal.pone.0262273 ◽

2022 ◽

Vol 17 (1) ◽

pp. e0262273

Author(s):

Carolina J. Delgado-Flores ◽

David García-Gomero ◽

Stefany Salvador-Salvador ◽

José Montes-Alvis ◽

Celina Herrera-Cunti ◽

...

Keyword(s):

Low Dose ◽

Prophylactic Treatment ◽

Hemophilia A ◽

Clotting Factor ◽

High Dose ◽

Bleeding Rate ◽

Episodic Treatment ◽

Grade Methodology ◽

Inform Decision Making ◽

Intermediate Dose

Background Different prophylactic and episodic clotting factor treatments are used in the management of hemophilia. A summarize of the evidence is needed inform decision-making. Objective To compare the effects of factor replacement therapies in patients with hemophilia. Methods We performed a systematic search in PubMed, Central Cochrane Library, and Scopus. We included randomized controlled trials (RCTs) published up to December 2020, which compared different factor replacement therapies in patients with hemophilia. Random-effects meta-analyses were performed whenever possible. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The study protocol was registered in PROSPERO (CRD42021225857). Results Nine RCTs were included in this review, of which six compared episodic with prophylactic treatment, all of them performed in patients with hemophilia A. Pooled results showed that, compared to the episodic treatment group, the annualized bleeding rate was lower in the low-dose prophylactic group (ratio of means [RM]: 0.27, 95% CI: 0.17 to 0.43), intermediate-dose prophylactic group (RM: 0.15, 95% CI: 0.07 to 0.36), and high-dose prophylactic group (RM: 0.07, 95% CI: 0.04 to 0.13). With significant difference between these subgroups (p = 0.003, I2 = 82.9%). In addition, compared to the episodic treatment group, the annualized joint bleeding rate was lower in the low-dose prophylactic group (RM: 0.17, 95% CI: 0.06 to 0.43), intermediate-dose prophylactic group (RM of 0.14, 95% CI: 0.07 to 0.27), and high-dose prophylactic group (RM of 0.08, 95% CI: 0.04 to 0.16). Without significant subgroup differences. The certainty of the evidence was very low for all outcomes according to GRADE methodology. The other studies compared different types of clotting factor concentrates (CFCs), assessed pharmacokinetic prophylaxis, or compared different frequencies of medication administration. Conclusions Our results suggest that prophylactic treatment (at either low, intermediate, or high doses) is superior to episodic treatment for bleeding prevention. In patients with hemophilia A, the bleeding rate seems to have a dose-response effect. However, no study compared different doses of prophylactic treatment, and all results had a very low certainty of the evidence. Thus, future studies are needed to confirm these results and inform decision making.

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High dose level radiation therapy for local tumour control in esthesioneuroblastoma

European Journal of Cancer ◽

10.1016/0959-8049(94)00324-x ◽

1994 ◽

Vol 30 (12) ◽

pp. 1757-1760 ◽

Cited By ~ 16

Author(s):

F. Guedea ◽

E. Van Limbergen ◽

W. Van Den Bogaert

Keyword(s):

Radiation Therapy ◽

Dose Level ◽

High Dose ◽

High Dose Level ◽

Tumour Control ◽

Local Tumour Control ◽

Local Tumour

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Dose-Response Effect and Dose-Toxicity in Stereotactic Radiotherapy for Brain Metastases: A Review

Cancers ◽

10.3390/cancers13236086 ◽

2021 ◽

Vol 13 (23) ◽

pp. 6086

Author(s):

Maxime Loo ◽

Jean-Baptiste Clavier ◽

Justine Attal Khalifa ◽

Elisabeth Moyal ◽

Jonathan Khalifa

Keyword(s):

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Local Control ◽

Stereotactic Radiotherapy ◽

Local Control Rate ◽

Dose Effect ◽

Published Data ◽

High Dose ◽

Single Fraction ◽

Fractionation Schedule

For more than two decades, stereotactic radiosurgery has been considered a cornerstone treatment for patients with limited brain metastases. Historically, radiosurgery in a single fraction has been the standard of care but recent technical advances have also enabled the delivery of hypofractionated stereotactic radiotherapy for dedicated situations. Only few studies have investigated the efficacy and toxicity profile of different hypofractionated schedules but, to date, the ideal dose and fractionation schedule still remains unknown. Moreover, the linear-quadratic model is being debated regarding high dose per fraction. Recent studies shown the radiation schedule is a critical factor in the immunomodulatory responses. The aim of this literature review was to discuss the dose–effect relation in brain metastases treated by stereotactic radiosurgery accounting for fractionation and technical considerations. Efficacy and toxicity data were analyzed in the light of recent published data. Only retrospective and heterogeneous data were available. We attempted to present the relevant data with caution. A BED10 of 40 to 50 Gy seems associated with a 12-month local control rate >70%. A BED10 of 50 to 60 Gy seems to achieve a 12-month local control rate at least of 80% at 12 months. In the brain metastases radiosurgery series, for single-fraction schedule, a V12 Gy < 5 to 10 cc was associated to 7.1–22.5% radionecrosis rate. For three-fractions schedule, V18 Gy < 26–30 cc, V21 Gy < 21 cc and V23 Gy < 5–7 cc were associated with about 0–14% radionecrosis rate. For five-fractions schedule, V30 Gy < 10–30 cc, V 28.8 Gy < 3–7 cc and V25 Gy < 16 cc were associated with about 2–14% symptomatic radionecrosis rate. There are still no prospective trials comparing radiosurgery to fractionated stereotactic irradiation.

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Evaluation of anti-ulcer activity of 4-hydrooxy benzalydehide against NSAIDs induced ulcers in rats

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20211878 ◽

2021 ◽

Vol 9 (5) ◽

pp. 1412

Author(s):

Rupali V. Jadhav ◽

V. K. Redasani ◽

Shankar B. Kalbhare ◽

Karishma Yadav ◽

Aryan Langeh ◽

...

Keyword(s):

Low Dose ◽

Positive Control ◽

Gastric Volume ◽

Control Group ◽

High Dose ◽

Antiulcer Activity ◽

Ulcer Index ◽

Pylorus Ligation ◽

The Impact ◽

Intermediate Dose

Background: The aim of this study was to evaluate antiulcer activity of 4-hydroxybenzaldehyde against NSAIDs induced ulcer in rats based differences in its morphology, distance with other external landmarks and also to sigmoid and transverse sinuses.Methods: The antiulcer activity of 4-HBD was evaluated using pylorus ligation-aspirin induced ulcer method. Animals of this models were treated with 4-HBD (50mg/kg, 100mg/kg and 150mg/kg).Results: It has been observed that 4-HBD at low dose (50mg/kg), intermediate dose (100mg/kg) and high dose (150mg/kg) showed significant increase in pH, significant decrease in gastric volume, significant decrease in ulcer index and significant decrease in total acidity.Conclusions: The impact of 4-HBD therapy with intermediate (100mg/kg, p.o.) dose was observed to be similar with the positive control group.

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ML-4 A case of primary CNS lymphoma diagnosed 5 years after stereotactic radiosurgery

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab159.087 ◽

2021 ◽

Vol 3 (Supplement_6) ◽

pp. vi23-vi23

Author(s):

Yusuke Tabei ◽

Ichirou Nakazato ◽

Kenichi Ooyama ◽

Masatou Kawashima ◽

Akira Matsuno ◽

...

Keyword(s):

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Tumor Cells ◽

Temporal Lobe ◽

Radiation Necrosis ◽

B Cell Lymphoma ◽

Unknown Primary ◽

High Dose ◽

Left Temporal Lobe ◽

The Right

Abstract Central nervous system primary malignant lymphoma (PCNSL) is rarely diagnosed as multiple metastatic brain tumors. Almost tumors recure early after receiving stereotactic radiosurgery (SRS). Regardless of the fact, the following case report displays PCNSL, diagnosed five years after the initial treatment with SRS as brain metastases of unknown primary origin. This extraordinal case suggests long-term follow-up regarding PCNCL. The case was a 55-year-old woman with a history of a total hysterectomy for cervical cancer. She developed left paralysis. Brain MRI confirmed a 27 mm contrast-enhanced lesion in the right frontal lobe and three other lesions. SRS was performed as a diagnosis of multiple brain metastases for urgent symptom relief. No extra-cranial cancerous lesions were found. Unknown primary cancer was a probable diagnosis at that time. Two years after SRS, local regrowth of tumor of the right frontal primary motor area was discovered. Re-irradiation was performed. Cerebral edema, contrast enhancement, and left paralysis progressed following five months, taking an oral corticosteroid. Craniotomy and debulk. The pathological diagnosis was brain radiation necrosis due to no viable tumor cells. New lesions in the left temporal lobe and basal ganglia appeared three years after surgery. Awake craniotomy was performed for the left temporal lobe lesion. Histopathology showed diffuse growth of tumor cells with a high nucleo-cytoplasmic ratio and irregular nuclear shape. Immunohistochemistry revealed positive CD10, CD20, CD45 (LCA), MUM1, and negative CD3, CD5. The Ki- 67 labeling rate was as high as almost 100% to diagnose diffuse large B-cell lymphoma, PCNSL. Multidrug chemotherapy consisting of rituximab, high-dose methotrexate, procarbazine, and vincristine were performed. Complete remission was obtained without any serious adverse events. Considering the residual radiation necrosis, whole-brain irradiation was avoided. Moreover, consolidation therapy was performed only with high-dose cytarabine therapy.

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