The Dosimetric Outcome of a Rotational Planning Target Volume in Patients With Oropharyngeal Cancers.

An isotropic expanded Planning Target Volume (PTV) neglects patient's off-axis rotation. This study designs a rotational PTV that is used instead of the standard 3-mm Clinical Target Volume (CTV) expanded PTV in oropharyngeal cancers with the goal to reduce pharyngeal constrictor muscle (PCM) mean dose. 10 patients were retrospectively evaluated. For off-axis rotation, the image was rotated around the longitudinal axis (cervical spinal canal) ± 5 degrees. These new CTVs were combined to form the rotational PTV. The standard and rotational treatment plans were designed with the goal to keep the superior and middle PCM-CTV70 mean dose to less than 50 Gy. There were a 355 cGy reduction in the superior PCM mean dose (form 5332 to 4977 cGy) and a 506 cGy reduction in middle PCM mean dose (from 4185 to 3679 cGy). 60% of patients may have at least a 20% reduction in dysphagia probability based on a Normal Tissue Complication Probability (NTCP) formula. The superior and middle PCM mean dose were reduced to less than 50 Gy in 40 and 20% of cases. There was an association between superior PCM mean dose and overlap volume of PTV70 and superior PCM in both standard (r = 0.92, p = 0.001) and rotational (r = 0.84, p = 0.002) plans. This association was present for middle PCM and PTV70 (r = 0.52, p = 0.02 and r = 0.62, p = 0.006). Rotational PTV can lower the mean dose to superior and middle PCMs, ultimately leading to lower dysphagia rates.

The effect of designing a rotational planning target volume on sparing pharyngeal constrictor muscles in patients with oropharyngeal cancer.

BACKGROUND: Planning target volume (PTV) has been used to account for variations in tissue, patient and beam position. In oropharyngeal cancers, an isotropic expanded PTV has been used. AIM: The aim of this study was to design a new margin formula that would cover the space occupied by an oropharyngeal clinical target volume (CTV) with ±5-degree rotation around the spine in order to reduce the pharyngeal constrictors overlap with PTV compared to an isotropic expanded PTV. METHODS: We retrospectively evaluated 20 volumetric-modulated arc therapy (VMAT) plans. In order to perform an off-axis rotation, a hypothetical point was placed through the center of the cervical spinal canal and the image was then rotated around the longitudinal axis ±5 degrees. This created a new set of CTVs that were combined to form the new rotational PTV. The overlap between the pharyngeal constrictor muscles (PCMs) and both PTVs was then evaluated. RESULTS: The new rotational PTV causes reduction in the superior PCM overlap in the base of tongue (BOT) lesions compared to tonsillar lesion, 57.8% vs 25.8%, P = 0.01, as well as middle PCM overlap, 73% vs 49%, P = 0.04. Average percent change for PTV volume and overlap with the superior, middle, and inferior PCMs are as followed: -19%, -37%, -59.4%, and -45.2. The smallest isotropic expansion that covers the new rotational PTV was between 3 and 5mm with the average tumor center shift of 0.49 cm. CONCLUSION: This new rotational PTV causes significant reduction of the overlap volume between PCMs and PTVs in order to spare the PCMs compared to isotropic expanded PTV.

Ru-106 plaque radiotherapy for vasoproliferative tumors of retina: a 15-year single-center experience.

PURPOSE: This study evaluates the outcomes of ruthenium-106 (Ru-106) plaque brachytherapy for vasoproliferative tumors (VPTs) of the ocular fundus in a single referral ocular oncology center. METHODS: The clinical charts of all patients diagnosed with VPT who underwent plaque radiotherapy from 2002 to 2017 were reviewed. Clinical features, types of treatment, outcomes and complications were evaluated. RESULTS: Of 46 patients with VPT diagnosis in our ocular oncology clinic, 25 (54.34%) cases were treated with Ru-106 plaque brachytherapy. Eleven patients (44%) were male, and the mean age at the time of diagnosis was 40.92 ± 13.11 years. The mean follow-up time was 47.56 ± 36.87 months. Inferotemporal quadrant was the most common site of the tumor (64.00%). The mean delivered apex and scleral dose was 101.56 ± 6.51 and 412.26 ± 113.66 Gray (Gy), respectively. Initial tumor length, width and thickness were 10.26 ± 3.42, 8.05 ± 2.83 and 4.27 ± 1.10 mm, respectively. The mean tumor thickness decreased to 2.60 ± 0.63 mm, postoperatively. Complete resolution of subretinal fluid around the tumor was achieved in 81.80% of cases. Visual acuity was more than 20/400 in 64% of patients before treatment and 60% of patients at last follow-up. CONCLUSION: Our study showed that Ru-106 plaque radiotherapy is an effective and safe method of treatment in VPTs.

Pain management of acute limb trauma patients with intravenous lidocaine in emergency department.

INTRODUCTION: This study was designed to assess the possible superiority of intravenous lidocaine to morphine for pain management. METHODS: This was a randomized double blind controlled superiority trial, carried on in the emergency department (ED). Traumatic patients older than 18-year-old with the complaint of acute pain greater than 4 on a numeric rating scale (NRS) from 0 to 10 on their extremities were eligible. One group received IV lidocaine (1.5 mg/kg), and the other received IV morphine (0.1mg/kg). Pain scores and adverse effects were assessed at 15, 30, 45 and 60 minutes and patients' satisfaction was evaluated two hours later. A minimum pain score reduction of 1.3 from baseline was considered clinically significant. RESULTS: Fifty patients with the mean age of 31.28±8.7 were enrolled (78% male). The demographic characteristics and pain scores of the two groups was similar. The on-arrival mean pain scores in two groups were, lidocaine: 7.9±1.4 and morphine: 8.0±1.4 (p=0.57) and after 1 hour were, lidocaine: 2.28±1.2 and morphine: 3.2±1.7. Although the pain score decreased significantly in both group (p=0.027), there were not any clinically and statistically significant difference between the two groups (p=0.77). Patients' satisfaction with pain management in both groups were almost similar (p=0.49). CONCLUSION: The reduction in pain score using IV lidocaine is not superior to IV morphine in adult ED patients with traumatic limb pain.

Abdominal and pelvic CT scan interpretation of emergency medicine physicians compared with radiologists' report and its impact on patients' outcome.

PURPOSE: In this study, the impact of contrast-enhanced abdominopelvic CT scan interpretations by emergency medicine team on patients' morbidity and mortality was evaluated and their interpretations were compared to radiologists' reports. METHODS: During a 3-month period, all patients who had undergone a contrast-enhanced abdominopelvic CT scan at the emergency department enrolled in this study. All CT scans were interpreted blindly by the emergency medicine (ED) attending physicians and the patients were treated accordingly. Radiologists reported all the CT scans within 12 h. Radiologists' reports were put into the agreement or disagreement group retrospectively. A panel of experts further evaluated the disagreement groups' medical charts and placed them in clinically significant or insignificant group based on the follow-up for 28 days. RESULTS: In this study, 170 CT scans were interpreted. The agreement rate was 68.2%. In the clinically significant disagreement group, eight patients did not receive the required treatment and three patients were over treated. Although the overall mortality rate was 5, none could have been prevented by a prompt radiologist's report. The disagreement group had longer hospital stay (p = 0.006) and transfer to other wards (p = 0.035). The inter-rater reliability between emergency medicine attending physicians and attending radiologists was substantial (kappa = 0.77) and statistically significant (p < 0.0001). CONCLUSION: Our findings support the cautious use of ED physicians' CT scan interpretations for patients' management. Ideally, the ED physicians should utilize a real-time radiologist interpretation in critical patients. This collaboration will result in better patient management.

Ketamine-propofol combination (ketofol) vs propofol for procedural sedation and analgesia: systematic review and meta-analysis.

OBJECTIVE: This meta-analysis of trials was conducted to evaluate the analgesic and side effects of ketamine-propofol combination (ketofol) in comparison to propofol in procedural sedation and analgesia (PSA). METHODS: Medline, EMBASE, Scopus, CINHAL, and Cochrane Central Register of Controlled Trials were searched for clinical trial. The administration complications were the key outcomes of interest. RESULT: Eighteen clinical trials that met our criteria were included in the analysis. Pooling of data showed that ketofol is significantly effective for reduction of respiratory complication and with relative risk (RR) of 0.31 in 14 trials (95% confidence interval [CI], 0.47-0.7; P = .001). Ketofol was also effective in reducing cardiovascular complications with hypotension RR of 0.11 in 9 trials (95% CI, 0.17-0.97; P = .04) and bradycardia RR of 0.47 in 8 trials (95% CI, 0.28-0.72; P = .008). The present study also showed that the summary of RR for psychomimetic complications was 1.95 in 13 trials were (95% CI, 0.79-4.81; P = .15) and for muscle rigidity was 0.52 for 2 trials (95% CI, 0.06-4.67; P = .56), and both were insignificant. In regard to nausea and vomiting, the RR was 1.23 in 12 trials (95% CI, 0.39-3.88; P = .72) and insignificant. CONCLUSION: This meta-analysis demonstrates good safety profile in cardiorespiratory problems and comparable rate of other complications with propofol in adult procedural sedation and analgesia.

Comparing the brain CT scan interpretation of emergency medicine team with radiologists' report and its impact on patients' outcome.

Requesting non-enhanced brain CT scans for trauma and non-trauma patients in ER is very common. In this study, the impact of incorrect brain CT scan interpretations by emergency medicine team on patients' primary and secondary outcome was evaluated in the setting where neuroradiologist reports are not always available. During a 3-month period, 450 patients were enrolled and followed for 28 days. All CT scans were interpreted by the emergency medicine team, and the patients were managed accordingly. Neuroradiologists' reports were considered as gold standard, and the patients were then grouped into the agreement or disagreement group. A panel of experts further evaluated the disagreement group and placed them in clinically significant and insignificant. The agreement rate between emergency medicine team and neuroradiologists was 86.4 %. The inter-rater reliability between emergency team and neuroradiologists was substantial (kappa = 0.68) and statistically significant (p < 0.0001). Only five patients did not receive the necessary management, and among them, only one patient died, and 12 patients received unnecessary management including repeated CT scan, brain MRI, and lumbar puncture. Forty-one patients were managed clinically appropriate in spite of misinterpretation. A 28-day follow-up showed a mortality rate of 0.2 %; however, expert panel believed the death of this patient was not related to the CT scan misinterpretation. We conclude that although the disagreement rate in this study was 13.6 %, primary and secondary outcomes were not clinically jeopardized according to the expert panel idea and 28-day follow-up results.

The impact of using RUSH protocol for diagnosing the type of unknown shock in the emergency department.

Clinical assessment and classification of shock is extremely difficult to conduct on critically ill patients especially upon arrival at the emergency department. Resuscitative point-of-care ultrasound could be used for rapid initial diagnosis and better management. In this study, the results of using the RUSH (Rapid Ultrasound in Shock) exam to determine the type of shock in the emergency department are compared to the final diagnosis of patients. This was a single-center prospective study in which all patients with an unknown type of shock and no prior treatment were included. Parallel to the standard resuscitative management and diagnosis of the emergency team, the RUSH exam was performed blindly on the patient by an emergency medicine staff who was not part of the patient's caregiving team. The results of the RUSH exam were then compared to the final diagnosis of the patients and the 48-h outcome. Twenty-five patients were enrolled in this study. The overall kappa correlation of the RUSH exam compared with the final diagnosis was 0.84 which is an almost perfect agreement. The overall sensitivity of the RUSH exam was 88 % and the specificity was 96 %. Although the mortality rate was 64 %, there was not a significant relationship between mortality and the protocol used for diagnosis. The RUSH exam could be used in emergency wards to detect types of shock.

Nebulized fentanyl vs intravenous morphine for ED patients with acute limb pain: a randomized clinical trial.

OBJECTIVE: Intravenous morphine has been used as a common method of pain control in emergency care. Nebulized fentanyl is also an effective temporary substitute. This study was designed to compare the effectiveness of nebulized fentanyl with intravenous (IV) morphine on management of acute limb pain. METHODS: This was a placebo-controlled, double-blind randomized clinical trial. Ninety emergency department patients with moderate to severe pain aged 15 to 50 years were blocked randomized and enrolled in this study. Forty-seven patients in the experimental group received nebulized fentanyl (4 µg/kg) and IV normal saline as placebo, and the remaining 43 patients in the control group received IV morphine (0.1 mg/kg) and nebulized normal saline as placebo. All participants' pain scores were assessed by Numerical Rating Scale before and after intervention at 5-, 10-, 15-, 30-, 45-, and 60-minute intervals. Patients' vital sign and possible adverse effects were recorded respectively. Finally, all participants were assessed for their satisfaction. RESULTS: The mean initial pain score in the experimental group was 8.7 and 8.4 in the control group (P = .1). Pain relief in both groups after 5 and 10 minutes were similar (P = .72). Although the pain relief was significantly greater with fentanyl at 15 minutes, this difference is not clinically significant. Pain management in both groups was successful and was more than 3 scores reduction in Numerical Rating Scale. Patient satisfaction in both groups was similar. No adverse effects were reported in the experimental group. CONCLUSION: This study suggests that nebulized fentanyl is a rapid, safe, and effective method for temporary control of acute limb pain in emergency department patients.

Master Breast Radiation Planning: Simple Guide for Radiation Oncology Residents.

This article focuses on various aspects of breast radiation treatment planning, from simulation to field design. It covers the most common techniques including tangents, mono isocentric, dual isocentric, electron-photon match, and VMAT. This can serve as a guide for radiation oncology residents and medical students to advance their understanding of key aspects of breast radiation treatment and planning processes.

Multimodal radiotherapy dose prediction using a multi-task deep learning model.

BACKGROUND: In radiation therapy (RT), accelerated partial breast irradiation (APBI) has emerged as an increasingly preferred treatment modality over conventional whole breast irradiation due to its targeted dose delivery and shorter course of treatment. APBI can be delivered through various modalities including Cobalt-60-based systems and linear accelerators with C-arm, O-ring, or robotic arm design. Each modality possesses distinct features, such as beam energy or the degrees of freedom in treatment planning, which influence their respective dose distributions. These modality-specific considerations emphasize the need for a quantitative approach in determining the optimal dose delivery modality on a patient-specific basis. However, manually generating treatment plans for each modality across every patient is time-consuming and clinically impractical. PURPOSE: We aim to develop an efficient and personalized approach for determining the optimal RT modality for APBI by training predictive models using two different deep learning-based convolutional neural networks. The baseline network performs a single-task (ST), predicting dose for a single modality. Our proposed multi-task (MT) network, which is capable of leveraging shared information among different tasks, can concurrently predict dose distributions for various RT modalities. Utilizing patient-specific input data, such as a patient's computed tomography (CT) scan and treatment protocol dosimetric goals, the MT model predicts patient-specific dose distributions across all trained modalities. These dose distributions provide patients and clinicians quantitative insights, facilitating informed and personalized modality comparison prior to treatment planning. METHODS: The dataset, comprising 28 APBI patients and their 92 treatment plans, was partitioned into training, validation, and test subsets. Eight patients were dedicated to the test subset, leaving 68 treatment plans across 20 patients to divide between the training and validation subsets. ST models were trained for each modality, and one MT model was trained to predict doses for all modalities simultaneously. Model performance was evaluated across the test dataset in terms of Mean Absolute Percent Error (MAPE). We conducted statistical analysis of model performance using the two-tailed Wilcoxon signed-rank test. RESULTS: Training times for five ST models ranged from 255 to 430 min per modality, totaling 1925 min, while the MT model required 2384 min. MT model prediction required an average of 1.82 s per patient, compared to ST model predictions at 0.93 s per modality. The MT model yielded MAPE of 1.1033 ± 0.3627% as opposed to the collective MAPE of 1.2386 ± 0.3872% from ST models, and the differences were statistically significant (p = 0.0003, 95% confidence interval = [-0.0865, -0.0712]). CONCLUSION: Our study highlights the potential benefits of a MT learning framework in predicting RT dose distributions across various modalities without notable compromises. This MT architecture approach offers several advantages, such as flexibility, scalability, and streamlined model management, making it an appealing solution for clinical deployment. With such a MT model, patients can make more informed treatment decisions, physicians gain more quantitative insight for pre-treatment decision-making, and clinics can better optimize resource allocation. With our proposed goal array and MT framework, we aim to expand this work to a site-agnostic dose prediction model, enhancing its generalizability and applicability.

Meatal stenosis following three types of circumcision with frenular artery preservation (FAP), the Plastibell device (PD), and frenular artery ligation (FAL): a long-term follow-up.

BACKGROUND: Despite the simplicity of male circumcision, complications occur frequently. Post-circumcision meatal stenosis is a concerning complication that might require several interventions. AIM: This study aims to evaluate the incidence of meatal stenosis in long-term follow-up, following three common circumcision methods: frenular artery preservation, frenular ligation, and the Plastibell device. METHODS: This study is the continuation of the previous randomized clinical trial, the preliminary abstract of which has been accepted in the annual meeting of the American Urological Association in 2011. However, in this paper, we only included the patients with results of long-term follow-up. Patients were followed for a median of 11 years (range, 7-17). Follow-ups were recorded by evaluation of meatus and signs and symptoms of meatal stenosis. RESULTS: Two hundred six boys (80 neonates and 126 non-neonates) at the time of procedure were included in this study. The circumcision was conducted on 23.3% (48/206) of boys with the Plastibell device (PD) and 39.3% (81/206) of cases with frenular artery preservation (FAP) and 37.4% (77/206) of cases with frenular artery ligation (FAL). Meatal stenosis presented in 13 children during follow-up. Considering the three methods of circumcision, a significant difference in the incidence of meatal stenosis among the types of circumcisions was observed (6.3% in PD and 1.2% in FAP, 11.7% in FAL, P = 0.026). CONCLUSION: The present study revealed that the technique preserving the frenular artery is associated with a significantly lower incidence of meatal stenosis. Hence, the FAP is the recommended technique for circumcision as compared to two other methods.

Literature review of management of brain metastases from germ cell tumors.

OBJECTIVE: In this review article, we discuss the role of chemotherapy, surgery, and radiation therapy in the treatment of brain metastases from germ cell tumors (GCT). BACKGROUND: GCT rarely metastasize to the brain and there is limited data to guide management. Most instances of brain metastases occur in patients with non-seminomatous germ cell tumors (NSGCT). METHODS: We searched PubMed using the terms 'central nervous system (CNS) metastases' or 'brain metastases' and 'germ cell' from 2011 through August 2021. Review articles and prospective trials related to the treatment of brain metastases in GCT were included in addition to articles obtained by hand search of the references and clinical practice guidelines. CONCLUSIONS: We highlight the importance of using chemotherapy as first-line therapy in most situations. We discuss the very minimal data regarding surgery and its primary role when there is significant mass effect or brain shift. We also compare whole brain radiation therapy (WBRT) with the use of radiosurgery. We then provide overall recommendations based on the reviewed data and our experience as a referral center for GCT.

Neuroblastoma: Essential genetic pathways and current therapeutic options.

Neuroblastoma is a very diverse pediatric tumor that starts from the neural crest, and it is responsible over more than 15% of all juvenile cancer deaths. Clinical signs and symptoms are highly dependent on tumor origin and spread. Bone, lymph nodes, liver, intracranial and orbital tissues, lungs, and the central nervous system are frequently involved in metastatic neuroblastoma. Neuroblastoma enhances with contrast in Computed Tomography (CT) scans as a solid heterogeneous mass which might invade to adjacent ipsilateral or contralateral lymph nodes, tissues, and vessels. Whereas the Magnetic Resonance Imaging (MRI) acquires an acceptable diagnostic accuracy for detection of spinal cord and musculoskeletal metastases. Lorlatinib, a novel ALK inhibitor designed to overcome this resistance, is currently being tested in the New Approaches to Neuroblastoma Therapy (NANT) consortium. Aurora kinase inhibitors have been reported to disrupt MYCN, which is particularly attractive considering the lack of direct inhibitors targeting this driver in neuroblastoma. Sorafenib, a RAF kinase inhibitor, and newer PI3K inhibitors are being tested in children with neuroblastoma in an attempt to block the RAS pathway. Despite various therapies including chemotherapy, radiotherapy, immunotherapy and autologous stem cell transplantation in different neuroblastoma risk groups, most patients undergo surgical removal of the tumoral mass. This review is aimed to summarize the updated knowledge about the neuroblastoma, pathogenesis, it's essential genetic pathways and the current available therapeutic options for neuroblastoma.

Association between radiation dose to organs at risk and acute patient reported outcome during radiation treatment for head and neck cancers.

BACKGROUND: Associations between patient-reported outcomes and dose to organs at risk (OARs) may promote management and guide future investigations. METHODS: We retrospectively evaluated PROs and OAR dose in head and neck (H&N) cancer. RESULTS: In 169 patients, we identified weak associations between: "Difficulty swallowing/chewing" and increased mean RT dose to the oral cavity, larynx, pharyngeal constrictor muscles (PCM) and contralateral parotid; "choking/coughing" and larynx mean dose; "problems with mucus in mouth and throat" and oral cavity, contralateral parotid mean dose and parotid V30, contralateral submandibular gland and PCM mean dose; "difficulty with voice/speech" and oral cavity, contralateral parotid, contralateral submandibular gland and larynx mean dose; and "dry mouth" and ipsilateral submandibular gland, oral cavity and PCM mean dose. CONCLUSION: We identified weak associations between PRO and dose to OARs-these data can guide on treatment management, patient counseling, and serve as a baseline for future investigations.

Recurrent Pterygium: A Review.

PURPOSE: To summarize the recent evidence regarding different aspects of pterygium recurrence. METHODS: Human-based studies from PubMed, Scopus, and Google Scholar were identified using the following keywords: conjunctival disease, pterygium, recurrent pterygium, pterygium recurrence, pterygium management/surgery, conjunctival autograft (CAU), amniotic membrane graft/transplant, and adjuvant therapy (January 2009 to February 2021). We reviewed risk factors associated with the recurrence of pterygium, timing of recurrence, medical treatments to prevent from recurrence, and nonsurgical and surgical alternatives for management of recurrence. RESULTS: Dry eye disease, black race, and young age are considered definite risk factors for recurrence. However, fleshy appearance of the pterygium and preoperative size remain controversial. Surgical techniques such as excessive suturing, insufficient conjunctival graft size, thick conjunctival graft with remained Tenon tissue, and postoperative graft retraction are considered possible risk factors for recurrence. Using fibrin glue instead of sutures can further reduce recurrence rates. Although recurrence could occur even after many years, most recurrences happen in the first 3-6 months after surgery. Multiple kinds of adjuvant medications are used before, during, or after the operation including mitomycin C (MMC), 5-fluorouracil (5-FU), corticosteroids, and anti-vascular endothelial growth factors (anti-VEGFs). Multiple weekly subconjunctival 5-FU injections are shown to be safe and effective in halting the progression of recurrent pterygium. Although topical bevacizumab is found to inhibit the growth of impending recurrent pterygium, the effect is mostly temporary. CAU is superior to amniotic membrane transplantation in the treatment for recurrent pterygia. CONCLUSIONS: There is yet to be a panacea in treating recurrent pterygium. Currently, there is not a globally accepted recommendation for treating recurrent pterygium with anti-VEGFs or 5-FU as a nonsurgical treatment. We strongly recommend using MMC as an adjunct to surgery in recurrent cases, with consideration of its specific complications. CAU is the most effective surgical treatment for recurrent pterygium, and other new surgical therapies need further investigation.

Integrating Radiation Oncology Into Undergraduate Medical Education.

Cancer is one of the most important public health problems. However, medical education has not advanced at the same rate when it comes to cancer education. Currently, the United States Medical Licensing Examination subject examinations do not cover radiation oncology, prevention, and survivorship planning in its assessment model. Incorporating medical oncology and radiation oncology training into the undergraduate medical education curriculum can have a significant benefit in training future physicians. In this paper, we review current literature and propose some ideas that can help incorporate oncology, and specifically radiation oncology, into undergraduate medical education.

Patient reported outcomes in patients with head and neck cancer treated with concurrent chemoradiation with weekly versus bolus cisplatin.

BACKGROUND: Patient Reported Outcome (PRO) data comparing bolus (B-CP) with weekly (W-CP) cisplatin concurrent with radiation are lacking. METHODS: We performed a retrospective study comparing PRO among 99 patients with head and neck radiation, 26% who received concurrent B-CP and 73% treated with W-CP. RESULTS: W-CP patients had a higher Charlson comorbidity index (CCI) (P = .004). There were no differences in median cisplatin dose, PROs, percutaneous endoscopic gastrostomy (PEG) dependence or hospitalization between arms. Patients with a greater decline in their self-reported dysphagia score were more often PEG dependent at the end of radiation therapy (P = .03). There was also a trend toward PEG dependence with a higher maximum dysphagia score and greater change in aspiration score (P = .06). The maximum decline in white cell count and absolute neutrophil count were greater in the W-CP group (P = .04, P = .01). CONCLUSION: Both B-CP and W-CP are well tolerated. PROs do not suggest a benefit to W-CP.

Exploiting tumor position differences between deep inspiration and expiration in lung stereotactic body radiation therapy planning.

PURPOSE: We demonstrate proof of principle that normal tissue doses can be greatly reduced in lung stereotactic body radiation therapy (SBRT) for mobile tumors, if the delivered dose is split between opposite respiratory states. METHODS: Patients that underwent 5 fraction lung SBRT at our institution and had deep inspiration breath hold (DIBH) and free breathing 4D computed tomography scans were included. Volumetric modulated arc therapy plans were generated on both respiratory phases and a third composite plan was generated delivering half the dose using the DIBH plan and the other half using the expiratory phase plan for each fraction. Computed tomography scans for the composite plan were fused based on ribs adjacent to the tumor to evaluate the dose volume histogram of critical structures. RESULTS: Four patients with 4 total tumors had requisite planning scans available. Tumor size was between 0.7 to 2.9 cm and tumor movement 1.4 to 2.9 cm. Median reduction in the chest wall (CW) V30Gy for the composite plan was 74.6% (range 33.7 to 100%), 76.9% (range 32.9 to 100%), and 89.3% (range 69.5 to 100%) compared to the DIBH, expiration phase, and free breathing plans, respectively. Median reduction in CW maximum dose for the composite plan was 23.3% (range 0.27% to 46.4%), 23.5% (range 3.2 to 48.2%), and 23.4% (range 0.27% to 48.4%) compared to the DIBH, expiration phase, and free breathing plans, respectively. Greater reduction in CW maximum dose was observed when patients had no overlap in planning target volumes between DIBH and expiration phases (median reduction 43.9% for no overlap vs 2.7% with overlap). Between all plans, lung V20Gy absolute differences were within 1.3%. For 2 of 4 patients, the composite plan met constraints for 3 fraction SBRT, while standard plans did not. CONCLUSIONS: We conclude that composite DIBH-expiration SBRT planning has the potential to improve organ at risk sparing.

Frontline Science: Escherichia coli use LPS as decoy to impair neutrophil chemotaxis and defeat antimicrobial host defense.

Bacterial infections and sepsis are leading causes of morbidity and mortality in critically ill patients. Currently, there are no effective treatments available to improve clinical outcome in sepsis. Here, we elucidated a mechanism by which Escherichia coli (E. coli) bacteria impair neutrophil (PMN) chemotaxis and we studied whether this mechanism can be therapeutically targeted to improve chemotaxis and antimicrobial host defense. PMNs detect bacteria with formyl peptide receptors (FPR). FPR stimulation triggers mitochondrial ATP production and release. Autocrine stimulation of purinergic receptors exerts excitatory and inhibitory downstream signals that induce cell polarization and cell shape changes needed for chemotaxis. Here we show that the bacterial cell wall product LPS dose-dependently impairs PMN chemotaxis. Exposure of human PMNs to LPS triggered excessive mitochondrial ATP production and disorganized intracellular trafficking of mitochondria, resulting in global ATP release that disrupted purinergic signaling, cell polarization, and chemotaxis. In mice infected i.p. with E. coli, LPS treatment increased the spread of bacteria at the infection site and throughout the systemic circulation. Removal of excessive systemic ATP with apyrase improved chemotaxis of LPS-treated human PMNs in vitro and enhanced the clearance of E. coli in infected and LPS-treated mice. We conclude that systemic ATP accumulation in response to LPS is a potential therapeutic target to restore PMN chemotaxis and to boost the antimicrobial host immune defense in sepsis.