Clinical Experience of Axillary Radiotherapy for Node-positive Breast Cancer.

AIMS: Patients with breast cancer who have positive lymph nodes are currently recommended axillary node clearance (ANC) or regional nodal irradiation (RNI). ANC is associated with complications such as lymphoedema, brachial plexopathy and shoulder stiffness. The AMAROS Group showed RNI to be non-inferior to ANC with regards to survival and recurrence, and with a better quality of life. We conducted a large real-world population study to show our centre's experience with the use of RNI and to contribute to the current discussion around the management of node-positive breast cancer. MATERIALS AND METHODS: We evaluated patients who received RNI as opposed to ANC between 2006 and 2009 (n = 190). Patients had a range of cancer subtypes/grades. All had positive axillary disease, identified by axillary node sampling or sentinel lymph node biopsy. Systemic therapy was given as per standard protocol. Our data were compared with those of patients who had RNI (n = 681) in AMAROS. Patients were followed up retrospectively and overall survival, breast cancer-specific survival, distant metastasis-free survival, locoregional recurrence and toxicity were recorded, including lymphoedema, brachial plexopathy and shoulder stiffness. Survival analysis was performed on R via the Kaplan-Meier method. Univariate and multivariate analyses were also performed. Toxicity data were reported as percentages. Patients meeting POSNOC trial criteria (one to two positive sentinel lymph nodes, macrometastasis, receiving adjuvant chemotherapy) including if oestrogen receptor-positive (stratified POSNOC) were identified for subgroup analysis in the regression model. RESULTS: Locoregional recurrence was 3.16% versus AMAROS RNI of 1.82%. Overall survival was slightly lower in our population, but cancer-specific survival was higher than AMAROS. Lymphoedema rates were 5.8% versus AMAROS 11% in RNI and 23% in ANC arms, respectively. Brachial plexopathy was 1.6% and arm/shoulder stiffness 7.4%. AMAROS conducted a quality of life survey pertaining to arm/shoulder stiffness, mobility and function, which seemed to affect about 18% in the RNI arm. Univariate analysis revealed POSNOC status, especially if also oestrogen receptor-positive, to be a low risk group with hazard ratio 0.42 (0.20-0.83, P = 0.015). Extracapsular extension of lymph node metastasis was a poor prognostic factor; hazard ratio 4.39 (1.45-14.0, P = 0.009). CONCLUSION: We support the conclusion of the AMAROS trial with survival and recurrence following RNI being non-inferior to ANC, and with similarly favourable toxicity data. We support the continuing use of RNI as a treatment option for patients with node-positive breast cancer. Further research is required to answer the key questions regarding personalised management for node-positive breast cancer, with regards to de-escalation and also intensification for the patients exhibiting adverse tumour biology.

Brachial Plexus Nerve Injuries and Disorders: MR Imaging-Ultrasound Correlation.

Multimodality imaging of the brachial plexus is essential to accurately localize the lesion and characterize the pathology and site of injury. A combination of computed tomography (CT), ultrasound, and MR imaging is useful along with clinical and nerve conduction studies. Ultrasound and MR imaging in combination are effective to accurately localize the pathology in most of the cases. Accurate reporting of the pathology with dedicated MR imaging protocols in conjunction with Doppler ultrasound and dynamic imaging provides practical and useful information to help the referring physicians and surgeons to optimize medical or surgical treatment regimens.

Natural History of Brachial Plexus, Peripheral Nerve, and Spinal Schwannomas.

BACKGROUND: Management of sporadic schwannomas is often dictated by a patient's clinical presentation and the tumor's behavior. For patients who are managed nonsurgically, there are little data available about the expected natural history. OBJECTIVE: To evaluate the natural history and growth patterns of extracranial schwannomas including tumors of the distal peripheral nerves, spine, and brachial plexus. METHODS: A retrospective review was performed to identify patients with nonsyndromic extracranial schwannomas at a single tertiary care institution diagnosed between 2002 and 2019. Patient data and tumor characteristics including volume were recorded. RESULTS: Two hundred twenty-seven patients were identified (mean age 51 years, 42% male, average of 27.8-month follow-up). Tumor location was distal peripheral nerve in 82, brachial plexus in 36, and paraspinal in 109. At the time of diagnosis, peripheral lesions were significantly larger than spinal (59 m 3 vs 13 cm 3 ) and brachial plexus lesions (15 cm 3 ). Distinct growth patterns were seen with both distal peripheral nerve and spinal lesions; 34/82 peripheral nerve lesions had fast growth (ß = 0.176%/day), and 48 had slow growth (ß = 0.021%/day; P < .01). Spinal schwannomas similarly had 30 fast-growing (ß = 0.229%/day), 16 moderate-growing (ß = 0.071%/day), and 63 slow-growing (ß = 0.022%/day; P = .03) subtypes. The brachial plexus had relatively homogeneous growth patterns (ß = 0.065%/day). Females had 2.9 times greater odds of having the fast-growing subtype. CONCLUSION: Distinct growth patterns were seen in extracranial sporadic schwannomas based on tumor location and patient demographics. Fast (>80% volume change per year) vs slow (5%-10% per year) tumor growth can often be ascertained within 2 follow-up images. Awareness of these patterns might have implications for patient counseling and therapeutic decision-making.

Nerve Imaging in the Wrist.

Neuropathic symptoms involving the wrist are a common clinical presentation that can be due to a variety of causes. Imaging plays a key role in differentiating distal nerve lesions in the wrist from more proximal nerve abnormalities such as a cervical radiculopathy or brachial plexopathy. Imaging complements electrodiagnostic testing by helping define the specific lesion site and by providing anatomical information to guide surgical planning. This article reviews nerve anatomy, normal and abnormal findings on ultrasonography and magnetic resonance imaging, and common and uncommon causes of neuropathy.

CLINICAL AND NEUROPHYSIOLOGICAL PARALLELS OF THE BRACHIAL PLEXOPATHY IN THE STRUCTURE OF NEUROGENIC THORACIC OUTLET SYNDROME.

OBJECTIVE: The aim: Was assessment of the neurophysiological data and features of clinical picture in patients with neurogenic thoracic outlet syndrome (TOS). PATIENTS AND METHODS: Materials and methods: 103 patients with upper extremity pain and/or paresthesia or hypotrophy, or a combination of these symptoms were examined. The examination algorithm included: cervical spine radiography, cervical spine and brachial plexuses magnetic resonance imaging (MRI), upper extremity soft tissues and vessels ultrasonic examination, stimulation electroneuromiography with F-waves registration. RESULTS: Results: Neurogenic TOS was diagnosed in 29 patients. A significant relationship between the following complaints and neurophysiological parameters was observed: pain, numbness during physical activity and decreased medial anrebrachial cutaneous nerve response amplitude by ≥25% compared to the contralateral side; hypothenar hypotrophy and decrease of ulnar nerve motor/sensory response amplitude; the 4-5th fingers hypoesthesia and decrease of ulnar nerve sensory response amplitude. CONCLUSION: Conclusions: Medial antebrachial cutaneous nerve amplitudes asymmetry indices of ≥25% or lack of response may be considered to be a marker of true neurogenic TOS.

Significant Asymmetry of the Bilateral Upper Extremities of a Skeleton Excavated from the Mashiki-Azamabaru Site, Okinawa Island, Japan.

The human skeleton of a young adult male with marked asymmetry of the bilateral upper extremities was excavated from the Mashiki-Azamabaru site (3000-2000 BCE) on the main island of Okinawa in the southwestern archipelago of Japan. The skeleton was buried alone in a corner of the cemetery. In this study, morphological and radiographic observations were made on this skeleton, and the pathogenesis of the bone growth disorder observed in the left upper limb was discussed. The maximum diameter of the midshaft of the humerus was 13.8 mm on the left and 21.2 mm on the right. The long bones comprising the left upper extremity lost the structure of the muscle attachments except for the deltoid tubercle of the humerus. The bone morphology of the right upper extremity and the bilateral lower extremities was maintained and was close to the mean value of females from the Ohtomo site in northwestern Kyushu, Japan, during the Yayoi period. It is assumed that the anomalous bone morphology confined to the left upper extremity was secondary to the prolonged loss of function of the muscles attached to left extremity bones. In this case, birth palsy, brachial plexus injury in childhood, and acute grey matter myelitis were diagnosed. It was suggested that this person had survived into young adulthood with severe paralysis of the left upper extremity due to injury or disease at an early age.

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

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.

Roles of preoperative and early postoperative electrodiagnosis in brachial plexus injury patients undergoing nerve transfer operations: retrospective feasibility study.

OBJECTIVE: The purpose of this retrospective observational study was to assess the feasibility of electrodiagnostic parameters, perioperatively, and to discover optimal values as prognostic factors for patients with brachial plexus injury undergoing nerve transfer operations. METHODS: We retrospectively reviewed the records of 11 patients who underwent nerve transfer surgery. The patients underwent perioperative electrodiagnosis (EDX) before and approximately 6 months after surgery. We evaluated the compound muscle action potential (CMAP) ratio, motor unit recruitment, and their interval changes. To evaluate motor strength, we used the Medical Research Council (MRC) grade, 6 and 12 months after surgery. We evaluated the relationships between improved CMAP ratio, and motor unit recruitment and MRC grade changes 6 and 12 months postoperatively. RESULTS: All parameters increased significantly after surgery. The CMAP ratio improvement 6 months after surgery correlated with the MRC grade change from baseline to 12 months, with a correlation coefficient of 0.813. CONCLUSION: EDX parameters improved significantly postoperatively, and the CMAP ratio improvement 6 months after surgery correlated with the clinical outcomes at 1 year. The results of perioperative EDX might help establish long-term treatment plans for patients who undergo nerve transfer surgery.

Cytokine profile and glial activation following brachial plexus roots avulsion injury in mice.

Inflammation and tissue infiltration by various immune cells play a significant role in the pathogenesis of neurons suffering the central nervous systems diseases. Although brachial plexus root avulsion (BPRA) leads to dramatic motoneurons (MNs) death and permanent loss of function, however, the knowledge gap on cytokines and glial reaction in the spinal cord injury is still existing. The current study is sought to investigate the alteration of specific cytokine expression patterns of the BPRA injured spinal cord during an acute and subacute period. The cytokine assay, transmission electron microscopy, and histological staining were utilized to assess cytokine network alteration, ultrastructure morphology, and glial activation and MNs loss within two weeks post-injury on a mouse unilateral BPRA model. The BPRA injury caused a progressively spinal MNs loss, reduced the alpha-(α) MNs synaptic inputs, whereas enhanced glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule-1 (IBA-1), F4/80 expression in ipsilateral but not the contralateral spinal segments. Additionally, cytokine assays revealed BPRA significantly altered the level of CXCL1, ICAM1, IP10, MCP-5, MIP1-α, and CD93. Notably, the elevated MIP1-α was mainly expressed in the injured spinal MNs. While the re-distribution of CD93 expression, from the cytoplasm to the nucleus, occasionally occurred at neurons of the ipsilateral spinal segment after injury. Overall, these findings suggest that the inflammatory cytokines associated with glial cell activation might contribute to the pathophysiology of the MNs death caused by nerve roots injury.

Anatomy, Imaging, and Pathologic Conditions of the Brachial Plexus.

The brachial plexus is an intricate anatomic structure with an important function: providing innervation to the upper extremity, shoulder, and upper chest. Owing to its complex form and longitudinal course, the brachial plexus can be challenging to conceptualize in three dimensions, which complicates evaluations in standard orthogonal imaging planes. The components of the brachial plexus can be determined by using key anatomic landmarks. Applying this anatomic knowledge, a radiologist should then be able to identify pathologic appearances of the brachial plexus by using imaging modalities such as MRI, CT, and US. Brachial plexopathies can be divided into two broad categories that are based on disease origin: traumatic and nontraumatic. In the traumatic plexopathy group, there are distinct imaging findings and management methods for pre- versus postganglionic injuries. For nontraumatic plexopathies, having access to an accurate patient history is often crucial. Knowledge of the timing of radiation therapy is critical to diagnosing post-radiation therapy brachial plexopathy. In acute brachial neuritis, antecedent stressors occur within a specific time frame. Primary and secondary tumors of the brachial plexus are not uncommon, with the most common primary tumors being peripheral nerve sheath tumors. Direct extension and metastasis from primary malignancies such as breast and lung cancer can occur. Although diagnosing a brachial plexus anomaly is potentially perplexing, it can be straightforward if it is based on foundational knowledge of anatomy, imaging findings, and pathologic features. ©RSNA, 2020.

Upregulation of JHDM1D-AS1 alleviates neuroinflammation and neuronal injury via targeting miR-101-3p-DUSP1 in spinal cord after brachial plexus injury.

BACKGROUND: Neuroinflammation in the spinal cord following acute brachial plexus injury (BPI) remains a vital cause that leads to motor dysfunction and neuropathic pain. In this study, we aim to explore the role of long non-coding RNA JHDM1D antisense 1 (JHDM1D-AS1) in mediating BPI-induced neuroinflammation and neuronal injury. METHODS: A total brachial plexus root avulsion (tBPRA) model in adult rats and IL-1ß-treated motor neuron-like NSC-34 cells and LPS-treated microglia cell line BV2 were conducted for in vivo and in vitro experiments, respectively. The expressions of JHDM1D-AS1, miR-101-3p and DUSP1, p38, NF-κB, TNF-α, IL-1ß, and IL-6 were detected by RT-PCR and western blot seven days after tBPI. Immunohistochemistry (IHC) was used to detect neuronal apoptosis. CCK8 assay, Tunel assay and LDH kit were used for the detection of neuronal injury. The targeted relationships between JHDM1D-AS1 and miR-101-3p, miR-101-3p and DUSP1 were verified by RNA immunoprecipitation (RIP) and dual-luciferase reporter gene assay. RESULTS: We found significant downregulated expression of JHDM1D-AS1 and DUSP1 but upregulated expression of miR-101-3p in the spinal cord after tBPI. Overexpression of JHDM1D-AS1 had a prominent neuroprotective effect by suppressing neuronal apoptosis and microglial inflammation through reactivation of DUSP1. Further exploration revealed that JHDM1D-AS1 may act as a competitive endogenous RNA targeting miR-101-3p, which bound on the 3'UTR of DUSP1 mRNA. In addition, overexpression of miR-101-3p could reverse the neuroprotective effects of JHDM1D-AS1 upregulation by blocking DUSP1. CONCLUSIONS: JHDM1D-AS1 exerted neuroprotective and anti-inflammatory effects in a rat model of tBPI by regulating miR-101-3p/DUSP1 axis.

Local Riluzole Release from a Thermosensitive Hydrogel Rescues Injured Motoneurons through Nerve Root Stumps in a Brachial Plexus Injury Rat Model.

The C5-C6 nerve roots are usually spared from avulsion after brachial plexus injury (BPI) and can thus be used as donors for nerve repair. A BPI rat model with C5-C6 nerve root stumps has been established in our previous work. The aim of this study was to test whether riluzole loaded into a thermosensitive hydrogel could applied locally in the nerve root stumps of this BPI rat model, thus increasing the reparative effect of the nerve root stumps. Nile red (a hydrophobic dye) was used as a substitute for riluzole since riluzole itself does not emit light. Nile red, loaded into a thermosensitive hydrogel, was added to the nerve root stumps of the BPI rat model. Additionally, eighteen rats, with operation on right brachial plexus, were evenly divided into three groups: control (Con), thermosensitive hydrogel (Gel) and thermosensitive hydrogel loaded with riluzole (Gel + Ri) groups. Direct nerve repair was performed after local riluzole release for two weeks. Functional and electrophysiological evaluations and histological assessments were used to evaluate the reparative effect 8 weeks after nerve repair. Nile red was slowly released from the thermosensitive hydrogel and retrograde transport through the nerve root stumps to the motoneurons, according to immunofluorescence. Discernible functional recovery began earlier in the Gel + Ri group. The compound muscle action potential, ChAT-expressing motoneurons, positivity for neurofilaments and S100, diameter of regenerating axons, myelin sheath thickness and density of myelinated fibers were markedly increased in the Gel + Ri group compared with the Con and Gel groups. Our results indicate that the local administration of riluzole could undergo retrograde transportation through C5-C6 nerve root stumps, thereby promoting neuroprotection and increasing nerve regeneration.

The role of arm volumes evaluation in the functional outcome and patient satisfaction following surgical repair of the brachial plexus traumatic injuries.

OBJECTIVE: Brachial plexus injuries are among the most complex injuries of the peripheral nervous system and among the most devastating injuries overall. In complete lesions, functional priorities include the reinnervation of the musculocutaneous and axillary nerves for proximal functions restoration. Three major nerves - radial, median, and ulnar - and the corresponding muscles remain denervated, which results in subsequent muscle atrophy. This study was aimed at the evaluation of arm volumes in surgically treated patients with brachial plexus injuries, in correlation with the type of palsy, recovery and associated factors. METHODS: The study included 36 patients with brachial plexus injuries who were surgically treated in our institution over a 15-year-long period. The evaluation of arm and arm segments volumes was carried out using water displacement testing, based on the Archimedes principle. RESULTS: Statistically significant differences were noted between the operated arm and the healthy arm in all of the measured segments (hands, forearms and upper arms), as well as between the patients with complete and upper palsy, and in correlation with the shoulder abduction recovery. CONCLUSIONS: Previous studies were mainly focused on the functional outcome and quality of life; although related to both, arm volumes in patients with brachial plexus injuries were not analyzed before. Significant differences between the operated arm and the healthy arm volumes, as well as between the various types of palsy, found in the present study should trigger further prospective research in relation to neurophysiology, useful functional recovery and quality of life.

Backpack palsy and other brachial plexus neuropathies in the military population.

Brachial plexus neuropathy is often seen in the military population, especially due to pressure (backpack palsy, BPP) or idiopathic (neuralgic amyotrophy, NA). We aimed to gain insight in the disease characteristics of soldiers with brachial plexus neuropathies in the Dutch military population and to compare disease characteristics between patients with BPP and NA. In this retrospective chart review study we aimed to include all patients with brachial plexus neuropathy, who presented in the Joint Military Hospital between 1 January, 2011 and 31 December, 2016. We calculated the incidence of NA and BPP and Chi-square tests or Student t tests were performed for differences in patient characteristics between NA and BPP. We included 127 patients, 63 with BPP, 45 with NA, 10 with traumatic brachial plexus neuropathy, and 9 with other plexopathy. The incidence of brachial plexus neuropathy was 50/100 000 person years overall, 25/100 000 person years for BPP, and 18/100 000 person years for NA. Patients in the BPP group differed from the NA with regard to pain (BPP 41% vs NA 93%, P = .000), atrophy (13% BPP vs 29% NA, P = .049), and sensory symptoms (83% BPP vs 44% NA, P = .000). In the BPP group 90% had incomplete recovery and in the NA group 78%. Our study showed a high incidence of BPP and NA in the military population and suggests recovery is not so benevolent as previously thought. Future research is necessary to improve insight and outcome of military patients with brachial plexus neuropathies.

Neuroprotection in the Acute Stage Enables Functional Recovery Following Repair of Chronic Cervical Root Transection After a 3-Week Delay.

BACKGROUND: Preganglionic cervical root transection (PCRT) is the most severe type of brachial plexus injury. In some cases, surgical procedures must be postponed for ≥3 wk until electromyographic confirmation. However, research works have previously shown that treating PCRT after a 3-wk delay fails to result in functional recovery. OBJECTIVE: To assess whether the immunosuppressive drug sirolimus, by promoting neuroprotection in the acute phase of PCRT, could enable functional recovery in cases of delayed repair. METHODS: First, rats received a left 6th to 8th cervical root transection, after which half were administered sirolimus for 1 wk. Markers of microglia, astrocytes, neurons, and autophagy were assessed at days 7 and 21. Second, animals with the same injury received nerve grafts, along with acidic fibroblast growth factor and fibrin glue, 3 wk postinjury. Sirolimus was administered to half of them for the first week. Mechanical sensation, grasping power, spinal cord morphology, functional neuron survival, nerve fiber regeneration, and somatosensory-evoked potentials (SSEPs) were assessed 1 and 23 wk postinjury. RESULTS: Sirolimus was shown to attenuate microglial and astrocytic proliferation and enhance neuronal autophagy and survival; only rats treated with sirolimus underwent significant sensory and motor function recovery. In addition, rats who achieved functional recovery were shown to have abundant nerve fibers and neurons in the dorsal root entry zone, dorsal root ganglion, and ventral horn, as well as to have SSEPs reappearance. CONCLUSION: Sirolimus-induced neuroprotection in the acute stage of PCRT enables functional recovery, even if surgical repair is performed after a 3-wk delay.

Characteristics of metastatic brachial plexopathy in patients with breast cancer.

PURPOSE: Brachial plexopathy in cancer patients is a rare but significant complication that causes pain and disability of the upper extremities. Clinical features of breast cancer patients with metastatic brachial plexopathy (MBP) have not been studied. We aimed to investigate the characteristics of MBP in breast cancer patients. METHODS: We retrospectively reviewed medical records of patients with breast cancer with MBP who visited Asan Medical Center from 2000 to 2016; we enrolled 44 patients. We comprehensively reviewed the characteristics, range of metastatic lymph nodes, initial symptoms, location, and severity of brachial plexus injury by electrodiagnostic study, radiologic findings, and associated complications. RESULTS: The mean age of patients with MBP was 51.9 ± 9.3 years; 25% were diagnosed with stage IV breast cancer at initial diagnosis. Weakness was the most common initial symptom of MBP (52.3%). Most patients showed limitation of shoulder range of motion and pain; 66% of patients exhibited malignant lymphedema. Forty-one patients were evaluated by electromyography; upper nerve trunk involvement (22.0%) was more frequent than lower nerve trunk involvement (9.8%). Nineteen patients underwent brachial plexus MRI, and supraclavicular area (SCA) metastasis was most frequent (57.9%). Sixteen patients were examined by both brachial plexus MRI and electromyography; patients with SCA metastasis exhibited significantly more frequent malignant lymphedema (p = 0.019) and upper nerve trunk involvement (p = 0.035), compared with patients with non-SCA metastasis. CONCLUSIONS: Our study revealed clinical features of MBP in breast cancer patients. Additional diagnostic evaluation focused on metastasis or aggravated metastatic tumor is needed when breast cancer patients are diagnosed with brachial plexopathy.

Incorporation of Biologic Response Variance Modeling Into the Clinic: Limiting Risk of Brachial Plexopathy and Other Late Effects of Breast Cancer Proton Beam Therapy.

PURPOSE: The relative biologic effectiveness (RBE) rises with increasing linear energy transfer toward the end of proton tracks. Presently, there is no consensus on how RBE heterogeneity should be accounted for in breast cancer proton therapy treatment planning. Our purpose was to determine the dosimetric consequences of incorporating a brachial plexus (BP) biologic dose constraint and to describe other clinical implications of biologic planning. METHODS AND MATERIALS: We instituted a biologic dose constraint for the BP in the context of MC1631, a randomized trial of conventional versus hypofractionated postmastectomy intensity modulated proton therapy (IMPT). IMPT plans of 13 patients treated before the implementation of the biologic dose constraint (cohort A) were compared with IMPT plans of 38 patients treated on MC1631 after its implementation (cohort B) using (1) a commercially available Eclipse treatment planning system (RBE = 1.1); (2) an in-house graphic processor unit-based Monte Carlo physical dose simulation (RBE = 1.1); and (3) an in-house Monte Carlo biologic dose (MCBD) simulation that assumes a linear relationship between RBE and dose-averaged linear energy transfer (product of RBE and physical dose = biologic dose). RESULTS: Before implementation of a BP biologic dose constraint, the Eclipse mean BP D0.01 cm3 was 107%, and the MCBD estimate was 128% (ie, 64 Gy [RBE = biologic dose] in 25 fractions for a 50-Gy [RBE = 1.1] prescription), compared with 100.0% and 116.0%, respectively, after the implementation of the constraint. Implementation of the BP biologic dose constraint did not significantly affect clinical target volume coverage. MCBD plans predicted greater internal mammary node coverage and higher heart dose than Eclipse plans. CONCLUSIONS: Institution of a BP biologic dose constraint may reduce brachial plexopathy risk without compromising target coverage. MCBD plan evaluation provides valuable information to physicians that may assist in making clinical judgments regarding relative priority of target coverage versus normal tissue sparing.

Examination of the human motor endplate after brachial plexus injury with two-photon microscopy.

INTRODUCTION: After traumatic nerve injury, neuromuscular junction remodeling plays a key role in determining functional outcomes. Immunohistochemical analyses of denervated muscle biopsies may provide valuable prognostic data regarding clinical outcomes to supplement electrodiagnostic studies. METHODS: We performed biopsies on nonfunctioning deltoid muscles in two patients after gunshot wounds and visualized the neuromuscular junctions using two-photon microscopy with immunohistochemistry. RESULTS: Although the nerves in both patients showed evidence of acute Wallerian degeneration, some of the motor endplates were intact but exhibited significantly decreased surface area and volume. Both patients exhibited substantial recovery of motor function over several weeks postinjury. DISCUSSION: Two-photon microscopic assessment of neuromuscular junction integrity and motor endplate morphometry in muscle biopsies provided evidence of partial sparing of muscle innervation. This finding supported the clinical judgment that eventual recovery would occur. With further study, this technique may help to guide operative decisionmaking after traumatic nerve injuries.