Estimating the Tolerance of Brachial Plexus to Hypofractionated Stereotactic Body Radiotherapy – A Modelling-based Approach from Clinical Experience.

Abstract Background: Brachial plexopathy (BP) is a potentially serious complication from stereotactic body radiation therapy (SBRT) that has not been widely studied. Therefore, we compared datasets from two different institutions and generated a brachial plexus dose-response model, to quantify what dose constraints would be needed to minimize the effect on normal tissue while still enabling potent therapy for the tumor.Methods: Two published SBRT datasets were pooled and modeled from patients treated with SBRT at Indiana University and the Richard Roudebush VAMC from 1998 to 2007, as well as the Karolinska Institute from 2008 to 2013. All patients in both studies were treated with SBRT for apically located lung tumors localized superior to the aortic arch. Toxicities were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and a probit dose response model was created with maximum likelihood parameter fitting.Results: This analysis includes a total of 89 brachial plexus Dmax values from both institutions. Among the 14 patients who developed BP, the most common complications were grade 2, comprising 7 patients. The median follow-up was 30 months (range 6.1-72.2) in the Karolinska dataset, and Indiana had a median of 13 months (range 1-71). Both studies had a median range of 3 fractions, but in the Indiana dataset 9 patients were treated in 4 fractions and the paper did not differentiate which ones were which, so our analysis is considered to be in 3-4 fractions, which is one of the main limitations. The probit model showed that the risk of BP with Dmax of 26 Gy in 3-4 fractions is 10%, and 50% with Dmax of 70 Gy in 3 -4 fractions.Conclusions: This analysis is only a preliminary result because more details are needed, and more comprehensive datasets are needed from a much broader cross-section of clinical practices. When more institutions join the QUANTEC and HyTEC methodology of reporting sufficient details to enable data pooling, our field will finally reach an improved understanding of human dose tolerance.

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Estimating the tolerance of Brachial Plexus to hypofractionated Stereotactic Body Radiotherapy – A modelling-based approach from clinical experience.

10.21203/rs.3.rs-100186/v2 ◽

2021 ◽

Author(s):

Irina Kapitanova ◽

Sharmi Biswas ◽

Sabrina Divekar ◽

Eric J Kemmerer ◽

Robert A Rostock ◽

...

Keyword(s):

Brachial Plexus ◽

Dose Response ◽

Medical Center ◽

Probit Model ◽

Brachial Plexopathy ◽

Response Model ◽

Clinical Practices ◽

Karolinska Institute ◽

Human Dose ◽

Dose Constraints

Abstract Background: Brachial plexopathy (BP) is a potentially serious complication from stereotactic body radiation therapy (SBRT) that has not been widely studied. Therefore, we compared datasets from two different institutions and generated a brachial plexus dose-response model, to quantify what dose constraints would be needed to minimize the effect on normal tissue while still enabling potent therapy for the tumor.Methods: Two published SBRT datasets were pooled and modeled from patients at Indiana University and the Richard L. Roudebush Veterans Administration Medical Center from 1998 to 2007, as well as the Karolinska Institute from 2008 to 2013. All patients in both studies were treated with SBRT for apically located lung tumors localized superior to the aortic arch. Toxicities were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and a probit dose response model was created with maximum likelihood parameter fitting.Results: This analysis includes a total of 89 brachial plexus Dmax values from both institutions. Among the 14 patients who developed BP, the most common complications were grade 2, comprising 7 patients. The median follow-up was 30 months (range 6.1-72.2) in the Karolinska dataset, and Indiana had a median of 13 months (range 1-71). Both studies had a median range of 3 fractions, but in the Indiana dataset 9 patients were treated in 4 fractions and the paper did not differentiate which ones were which, so our analysis is considered to be in 3-4 fractions, which is one of the main limitations. The probit model showed that the risk of BP with Dmax of 26 Gy in 3-4 fractions is 10%, and 50% with Dmax of 70 Gy in 3 -4 fractions.Conclusions: This analysis is only a preliminary result because more details are needed, and more comprehensive datasets are needed from a much broader cross-section of clinical practices. When more institutions join the QUANTEC and HyTEC methodology of reporting sufficient details to enable data pooling, our field will finally reach an improved understanding of human dose tolerance.

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Estimating the tolerance of brachial plexus to hypofractionated stereotactic body radiotherapy: a modelling-based approach from clinical experience

Radiation Oncology ◽

10.1186/s13014-021-01822-5 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Irina Kapitanova ◽

Sharmi Biswas ◽

Sabrina Divekar ◽

Eric J. Kemmerer ◽

Robert A. Rostock ◽

...

Keyword(s):

Brachial Plexus ◽

Dose Response ◽

Medical Center ◽

Probit Model ◽

Brachial Plexopathy ◽

Maximum Point ◽

Response Model ◽

Clinical Practices ◽

Karolinska Institute ◽

Human Dose

Abstract Background Brachial plexopathy is a potentially serious complication from stereotactic body radiation therapy (SBRT) that has not been widely studied. Therefore, we compared datasets from two different institutions and generated a brachial plexus dose–response model, to quantify what dose constraints would be needed to minimize the effect on normal tissue while still enabling potent therapy for the tumor. Methods Two published SBRT datasets were pooled and modeled from patients at Indiana University and the Richard L. Roudebush Veterans Administration Medical Center from 1998 to 2007, as well as the Karolinska Institute from 2008 to 2013. All patients in both studies were treated with SBRT for apically located lung tumors localized superior to the aortic arch. Toxicities were graded according to Common Terminology Criteria for Adverse Events, and a probit dose response model was created with maximum likelihood parameter fitting. Results This analysis includes a total of 89 brachial plexus maximum point dose (Dmax) values from both institutions. Among the 14 patients who developed brachial plexopathy, the most common complications were grade 2, comprising 7 patients. The median follow-up was 30 months (range 6.1–72.2) in the Karolinska dataset, and the Indiana dataset had a median of 13 months (range 1–71). Both studies had a median range of 3 fractions, but in the Indiana dataset, 9 patients were treated in 4 fractions, and the paper did not differentiate between the two, so our analysis is considered to be in 3–4 fractions, one of the main limitations. The probit model showed that the risk of brachial plexopathy with Dmax of 26 Gy in 3–4 fractions is 10%, and 50% with Dmax of 70 Gy in 3–4 fractions. Conclusions This analysis is only a preliminary result because more details are needed as well as additional comprehensive datasets from a much broader cross-section of clinical practices. When more institutions join the QUANTEC and HyTEC methodology of reporting sufficient details to enable data pooling, our field will finally reach an improved understanding of human dose tolerance.

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Axillary Artery Dissection and Thrombosis after Closed Proximal Humerus Fracture – a Rare Interdisciplinary Challenge

Zeitschrift für Orthopädie und Unfallchirurgie ◽

10.1055/a-0938-7041 ◽

2019 ◽

Vol 158 (04) ◽

pp. 406-413

Author(s):

Sam Razaeian ◽

Saad Rustum ◽

Lena Sonnow ◽

Rupert Meller ◽

Christian Krettek ◽

...

Keyword(s):

Early Diagnosis ◽

Brachial Plexus ◽

Functional Recovery ◽

Proximal Humerus Fracture ◽

Proximal Humerus ◽

Axillary Artery ◽

Low Energy ◽

Artery Dissection ◽

Brachial Plexopathy ◽

Rare Injury

Abstract Background Proximal humerus fractures account for 4 – 6% of all fractures and are a common result of low-energy trauma in the elderly. Concomitant neurovascular injury of the neighboring axillary artery and brachial plexus is a rarity, but has enormous impact on therapy, rehabilitation and prognosis. Diagnosis of axillary artery injury may be delayed due to its varied clinical presentation and lead to prolonged ischemia, distal necrosis and even loss of limb. Thorough clinical examination, high suspicion and identification of known predictors can be helpful in early diagnosis of this rare injury. Patients/Material and Methods We report a case of an intoxicated 76-year-old male who sustained a dislocated proximal humerus fracture, resulting in concomitant brachial plexopathy and axillary artery dissection with secondary thrombosis after a low-energy fall from standing height. Due to mistriage as a neurological emergency the somnolent patient presented under delayed circumstances at our traumatological emergency department, demonstrating pain, paleness, paralysis, paresthesia and non-palpable wrist pulses. Diagnosis was made through high suspicion after clinical examination with the aid of CT angiography. Emergent open reduction and anatomic shoulder hemiarthroplasty was performed followed by axillobrachial interposition grafting using a reversed saphenous vein graft and brachial plexus exploration. Results The surgical treatments were uncomplicated. The affected limb remains viable at 6-week follow-up; however, active shoulder function is limited due to residual brachial plexopathy. Conclusion Despite early diagnosis and management of this rare injury, the prognosis for functional recovery is guarded and largely dictated by the extent of neurological injury in the setting of concomitant brachial plexopathy. Brachial plexopathy is highly associated with axillary artery injury and its impact often underestimated in comparison due to its non-limb-threatening nature in the acute setting. Future studies should focus on the long-term prognosis for functional recovery in patients with this rare injury pattern.

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Changes in Post-Traumatic Symptom Pattern during and after Exposure to Extreme War Stress: An Uncontrolled, Preliminary Study Supporting the Dose-Response Model

Prehospital and Disaster Medicine ◽

10.1017/s1049023x00007640 ◽

2010 ◽

Vol 25 (1) ◽

pp. 38-41 ◽

Cited By ~ 2

Author(s):

Menachem Ben-Ezra ◽

Yuval Palgi ◽

Amit Shrira ◽

Dina Sternberg ◽

Nir Essar

Keyword(s):

Dose Response ◽

Medical Center ◽

External Stress ◽

Response Model ◽

Ptsd Symptoms ◽

Post Traumatic Stress ◽

War Stress ◽

Symptom Pattern ◽

Post Traumatic ◽

Stress Influences

AbstractIntroduction:Exposure to prolonged war stress is understudied. While there is debate regarding the empirical data of the dose-response model for post-traumatic stress disorder (PTSD), little is known about how weekly changes in external stress influences the level of PTSD symptoms. The purpose of this study was to measure the relation between objective external stress and PTSD symptoms across time, and thus, gain a deeper understating of the dose-response model.Hypothesis:The study hypothesis postulates that the more severe the external stressor, the more severe the exhibition of traumatic symptoms.Methods:Thirteen special army administrative staff (SAAS) members from the Rambam Medical Center in Haifa attended seven intervention meetings during the war. These personnel answered a battery of questionnaires regarding demographics and PTSD symptoms during each session. A non-parametric test was used in order to measure the changes in PTSD symptoms between sessions. Pearson correlations were used in order to study the relationship between the magnitude of external stressors and the severity of PTSD symptoms.Results:The results suggested that there was a significant relationship between the magnitude of external stressors and the severity of PTSD symptoms. These results are in line with the dose-response model.Conclusions:The results suggest that a pattern of decline in PTSD symptoms confirm the dose-response model for PTSD.

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On use of the multistage dose–response model for assessing laboratory animal carcinogenicity

Regulatory Toxicology and Pharmacology ◽

10.1016/j.yrtph.2007.03.002 ◽

2007 ◽

Vol 48 (2) ◽

pp. 135-147 ◽

Cited By ~ 8

Author(s):

Daniela K. Nitcheva ◽

Walter W. Piegorsch ◽

R.Webster West

Keyword(s):

Dose Response ◽

Laboratory Animal ◽

Response Model

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Human dose-response relationship for decompression and endogenous bubble formation

Journal of Applied Physiology ◽

10.1152/jappl.1990.69.3.914 ◽

1990 ◽

Vol 69 (3) ◽

pp. 914-918 ◽

Cited By ~ 69

Author(s):

R. G. Eckenhoff ◽

C. S. Olstad ◽

G. Carrod

Keyword(s):

Dose Response ◽

Continuous Wave ◽

Decompression Sickness ◽

Bubble Formation ◽

Nonlinear Least Squares ◽

Response Relationship ◽

Dose Response Relationship ◽

Continuous Wave Doppler ◽

Human Dose ◽

The Hill

The dose-response relationship for decompression magnitude and venous gas emboli (VGE) formation in humans was examined. Pressure exposures of 138, 150, and 164 kPa (12, 16, and 20.5 ft of seawater gauge pressure) were conducted in an underwater habitat for 48 h. The 111 human male volunteer subjects then ascended directly to the surface in less than 5 min and were monitored for VGE with a continuous-wave Doppler ultrasound device over the precordium or the subclavian veins at regular intervals for a 24-h period. No signs or symptoms consistent with decompression sickness occurred. However, a large incidence of VGE detection was noted. These data were combined with those from our previously reported experiments at higher pressures, and the data were fit to a Hill dose-response equation with nonlinear least-squares or maximum likelihood routines. Highly significant fits of precordial VGE incidences were obtained with the Hill equation (saturation depth pressure at which there is a 50% probability of detectable VGE [D(VGE)50] = 150 +/- 1.2 kPa). Subclavian monitoring increased the sensitivity of VGE detection and resulted in a leftward shift [D(VGE)50 = 135 +/- 2 kPa] of the best-fit curve. We conclude that the reduction in pressure necessary to produce bubbles in humans is much less than was previously thought; 50% of humans can be expected to generate endogenous bubbles after decompression from a steady-state pressure exposure of only 135 kPa (11 ft of seawater). This may have significant implications for decompression schedule formulation and for altitude exposures that are currently considered benign. These results also imply that endogenous bubbles arise from preexisting gas collections.

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