The authors have no acknowledgements.

Data on all patients treated with EBUS-guided cisplatin were reviewed. The institutional review board at the University of Florida approved this study (#IRB201400823). All data was prospectively collected and retrospectively analyzed. Use the following enrollment criteria.
1. Patient Selection
<ol>
	<li>Select patients between the ages of 18 and 80 years who have a biopsy-confirmed non-small cell lung cancer (NSCLC) or small cell lung carcinoma (SCLC) and have a pathologically-confirmed recurrence. Enroll patients who have received at least 50 gy of radiation to the hilar and mediastinal structures for 6 months or longer. Include patients with limited recurrence to the hilar, mediastinal, and peribronchial structures (lymph nodes, nodules, and masses) accessible through EBUS and distant metastases.</li>
	<li>Present all such patients to a multi-disciplinary thoracic oncology tumor board and obtain consensus on proceeding with the intratumoral cisplatin due to a lack of other localized therapeutic options. The decision to proceed with EBUS-guided ITC should be a joint recommendation of the institutional thoracic oncology tumor board.</li>
</ol>
2. Endobronchial Ultrasound (EBUS)-guided Cisplatin Injection
<ol>
	<li>Use a convex-probe EBUS, which has a built-in ultrasound probe on a flexible bronchoscope and enables real-time visualization of hilar, mediastinal, and peribronchial structures for ITC.</li>
	<li>Ensure that the patients abstain from oral food and fluids for at least 6 h prior to the procedure.</li>
	<li>Create an aqueous cisplatin solution at a concentration of 1 mg/mL with a maximal dose of 40 mg per session, based on previously-published literature9,10. Dissolve lyophilized cisplatin powder in 0.9% NaCl solution just before use.</li>
	<li>Give 10 mg of dexamethasone and 8 mg of ondansetron intravenously at the beginning of the procedure to prevent nausea.</li>
	<li>Perform the procedure with conscious sedation using midazolam and fentanyl intravenously (IV). Use topical anesthesia in the form of 5 mL of 4% lidocaine nebulization prior to the procedure.</li>
	<li>Start out with an IV injection of 2 mg of midazolam and 50 &#181;g of fentanyl. Reassess the patient every 1-2 min and give an additional 1 mg midazolam and 25 &#181;g fentanyl bolus to achieve and maintain conscious sedation (a minimally depressed consciousness such that the patient is able to continuously and independently maintain a patent airway, retain protective reflexes, and remain responsive to verbal commands and physical stimulation). Do not exceed the maximal permissible doses of fentanyl and midazolam, 200 &#181;g and 10 mg, respectively.</li>
	<li>Use standard monitoring, including a continuous 3-lead electrocardiogram monitoring the heart rate, continuous pulse oximetry, and respiratory rate measurements. Provide local anesthesia and supplemental O2 as required.</li>
	<li>&#160;Advance the scope through the vocal cords in the airways.&#160;Identify and locate the target lesion.</li>
	<li>Turn on the EBUS processor and inflate the balloon at the tip of the scope using 1-2 mL of normal saline. Flex the scope across the airway wall and locate the lesion. The location of the lesion will depend on CT/PET findings, but some of the common sites include the subcarinal area, the right and left paratracheal areas, and the right and left hilar areas.</li>
	<li>Deploy a 22 G EBUS needle that is housed in a sheath through the working channel of the scope and lock it in position. 
	NOTE: Although there are no precise surgical coordinates for the injection site, some of the commonly-treated sites include the subcarinal (medially at the junction of the left and right main bronchi), the right paratracheal (laterally at the right main bronchus, just above the right upper lobe orifice), the left paratracheal (at the junction of the distal trachea and the left main between the arch of the aorta and the left pulmonary artery), the right hilar (laterally at the proximal bronchus intermedius, below the right upper lobe opening), and the left hilar (at the junction of the left upper lobe and the left lower lobe bronchi).</li>
	<li>Under real-time ultrasound guidance, puncture the tracheobronchial wall and place the needle in the target lesion. Remove the stylet within the needle and inject cisplatin into the lesion 10 mL (1 mg/mL of cisplatin) at a time. Retract the needle within the sheet.</li>
	<li>Treat each lesion with four punctures per session at different locations to facilitate the injection of the medication throughout. Inject 10 mg of cisplatin per puncture.</li>
	<li>Treat one to two lesions per session. If more than one lesion is treated per session, inject each site with 20 mg of cisplatin, with total dose per session not exceeding 40 mg.</li>
	<li>Remove the needle from the working channel of the scope.</li>
	<li>Suction any additional drug from the distal airways and remove the bronchoscope.</li>
	<li>Allow the patients to recover as per hospital protocol and discharge them on the same day.</li>
	<li>Repeat the cisplatin injection (steps 2.7-2.13) once a week for a total of 4 weeks (on days 1, 8, 15, and 22). 
	NOTE: Once treated, a particular lesion should never be considered for retreatment with ITC on subsequent encounters.</li>
</ol>
3. Post-injection
<ol>
	<li>Evaluate the response by a follow-up chest computed tomography (CT) or a positron emission tomography (PET/CT) scan 8-12 weeks after the last treatment session. Define the local recurrence as the recurrence at the site of treatment and the regional recurrence as the recurrence in the mediastinum, hilum, or supraclavicular fossa.</li>
</ol>

<ol>
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The authors have nothing to disclose.

Our manuscript focuses on the management of isolated mediastinal and hilar recurrences of lung cancer for patients in whom more radiation is not an option. The incidence of IMHR is approximately 9%11. Different treatment options have been tried in these patients, including palliative chemotherapy, more external beam radiation therapy, or supportive care and surveillance. At our institution, we treat these patients with intratumoral cisplatin guided by bronchoscopy.
There has been a growing interest in intratumoral chemotherapy and immunotherapy over the last several years. One of the potential advantages of injecting chemotherapeutic agents into the tumor mass is that a significantly higher concentration (6-10 times) of the medication can be achieved in the tumor mass12. Cisplatin is commonly used for the treatment of lung cancer as a part of combination systemic chemotherapy13,14,and it has also been used intralesionally for head, neck, and malignant liver cancers15,16. Additionally, it has been utilized endoscopically for palliation of obstructive esophageal cancers17 and injected into gastric tumors18. Based on available evidence and experience, we chose to use cisplatin as the chemotherapeutic agent of choice for bronchoscopic ITC.
The critical step in this protocol involves the proper patient selection. All patients should demonstrate in-field recurrence from a previous disease, should present isolated disease in the chest, and should be discussed at a multidisciplinary tumor board to confirm their limited therapeutic options. From a procedural perspective, the ability to identify the site of recurrent disease on EBUS and to advance the needle reliably into the diseased node is important. Cisplatin should be injected into the tumor in 10 mL aliquots. An attempt must be made to inject 40 mg in four separate passes at different areas on the node. After injecting the drug, excess cisplatin should be suctioned from the distal airways. Due to concerns for developing bronchopleural fistula, concurrent radiation therapy to the same site is not recommended. Up to 2 sites can be treated in the same session. If more than one site is treated, each site should be injected with 20 mg of cisplatin.
In patients with stage III or stage IV NSCLC previously treated with chemotherapy who are treated with second-line chemotherapy, the median survival time is 4-10 months19,20. However, no studies to date have looked into the survival among patients with isolated hilar and mediastinal recurrence of lung cancer following full-dose radiation therapy. The overall median survival of 8 months in our cohort is comparable to the number quoted in existing literature and would suggest a survival benefit compared to best supportive care only. Additionally, the localized cisplatin injection is tolerated much better and has fewer side effects as compared to systemic chemotherapy.
There are several limitations to our study, including retrospective design. Although we have a very well-structured protocol, its performance outside of our institution has not been studied. Serum and tumor concentration of the drug were not analyzed, and some patients were receiving systemic therapy, which could have confounded the results. However, we believe that the response seen in our cohort can largely be attributed to localized cisplatin injection7,12.
EBUS-guided intratumoral injection of cisplatin is feasible, well-tolerated, and potentially safe and effective in patients with isolated hilar and mediastinal recurrence of lung cancer for whom no localized therapeutic options are available. Multicenter randomized trials should be conducted to further validate our findings.

Lung cancer is the most prevalent cancer worldwide in both men and women and accounts for 1 in 5 of all cancer-related deaths. It has a case fatality rate of 0.871,2. Recurrence after initial treatment accounts for most deaths in patients with lung cancer. Therapeutic options for recurrent lung cancer are limited. Recurrent lung cancer also leads to significant impairment in quality of life and to significant caregiver burnout and requires additional supportive care, all of which decrease the likelihood of acceptance and tolerance to further interventions3.
Nearly 30% of patients with NSCLC have locoregional recurrence after radiation4. Treatment options for these patients are limited and include systemic chemotherapy, which has an objective response rate of only 10%5,6. Although repeat chest radiation is feasible, it has been studied mainly for palliative purposes and symptom relief and has not been used for disease remission3.
At our institution, all patients with isolated mediastinal and hilar recurrence (IMHR) accessible through bronchoscopy were treated with an endobronchial ultrasound (EBUS)-guided transbronchial intratumoral injection of cisplatin (ITC). Concurrent treatment with systemic chemotherapy and/or external beam radiation therapy (EBRT) was allowed as per the treating oncologists&#39; discretions. This manuscript highlights the safety, efficacy, feasibility, and detailed methods of the protocol used at our institution.

<table><tbody><tr><td>Bronchoscope</td><td></td><td></td><td></td></tr><tr><td>22 Guage olympus EBUS needle</td><td></td><td></td><td></td></tr><tr><td>40 g of cisplatin in 40 mL of normal saline</td><td></td><td></td><td></td></tr></tbody></table>

endobronchial ultrasound-guided intratumoral injection of cisplatin for the treatment of isolated mediastinal recurrence of lung cancer

Isolated hilar and mediastinal recurrence (IMHR) following external beam radiation therapy (EBRT) in patients with lung cancer is common. These patients do not have many treatment options and are usually offered palliative chemotherapy or best supportive care. Endobronchial ultrasound (EBUS)-guided intratumoral injection of cisplatin (ITC) is a novel approach for these patients. The procedure is performed under conscious sedation. The lesion is located with a bronchoscopy using EBUS, and a 22-gauge EBUS needle is advanced through the working channel of the scope and locked in position. Under ultrasound guidance, the wall of the tracheobronchial tree is punctured and the needle is moved into the target lesion. The needle stylet is then removed and cisplatin (40 mg/40 mL) is injected into the lesion. One to two sites are treated per session. Details of the procedure are described in the protocol section of paper. At our center, 50 sites were treated in 36 patients (19 males, 17 females). The mean age of our cohort was 61.9 &#177;8.5 years. We performed final analyses on 35 patients and 41 sites. 24/35 (69%) had complete or partial response (responders), whereas 11/35 (31%) had stable or progressive disease (non-responders). Overall, survival in our group was 8 months (95% CI of 6-11 months), with patients who responded having significantly better survival than the ones who did not.

The response was measured by follow-up imaging 8-12 weeks after therapy. The response was classified as complete remission (CR), partial remission (PR), stable disease (SD), progressive disease (PD), or unable to assess response based on RECIST 1.1 criteria8. Patients with CR and PR were considered responders, and the others were classified as non-responders. Secondary outcomes included response based on tumor histology, size of recurrence, and concurrent systemic therapy. The side effects and feasibility of the protocol were also analyzed.
Kaplan-Meier curves were used to estimate the survival probabilities. The survival and PFS for responders versus non-responders was compared by the log-rank test. Associations between response rates and other factors were examined using Fisher&#39;s exact test.
Figure 1 shows a detailed distribution of patients, sites, and site-specific responses. The final analysis included 35 patients and 41 sites. 69% of the patients were classified as responders (24/35), and 31% were non-responders (11/35). Table 1 shows the outcomes of the treatment based on various sub-group analyses. The median survival for the group was 8 months (95% CI of 6-11 months): 10 months for responders (95% CI of 8-13 months) and 6 months for non-responders (95% CI of 3-10 months); this difference was statistically significant, with a p-value of 0.029 (Figure 2). Figure 3 shows the difference in PFS between responders and non-responders.
<img alt="Figure 1" src="/files/ftp_upload/54855/54855fig1.jpg" /> 
Figure 1: Number of Patients Analyzed and Their Outcomes. A detailed flow diagram of the number of patients and sites treated initially and the number of patients and sites presented here for final analysis. <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/54855/54855fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" src="/files/ftp_upload/54855/54855fig2.jpg" /> 
Figure 2: Kaplan-Meier Curves for Overall Survival in Months Amongst Responders and Non-responders. These curves show that patients who responded to therapy demonstrated statistically-significant overall survival as compared to non-responders. <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/54855/54855fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" src="/files/ftp_upload/54855/54855fig3.jpg" /> 
Figure 3: Kaplan-Meier Curves for Progression-free Survival in Months Amongst Responders and Non-responders. Patients who responded to treatment had statistically-significant improvements in progression-free survival. <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/54855/54855fig3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<table fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td></td>
			<td></td>
			<td>Responders</td>
			<td>Non Responders</td>
			<td>p value</td>
		</tr>
		<tr>
			<td>1</td>
			<td>Histology</td>
			<td></td>
			<td></td>
			<td>0.84</td>
		</tr>
		<tr>
			<td>-</td>
			<td>Adenoca</td>
			<td>13 (72%)</td>
			<td>5 (28%)</td>
			<td></td>
		</tr>
		<tr>
			<td>-</td>
			<td>Squamous</td>
			<td>7 (58%)</td>
			<td>5 (42%)</td>
			<td></td>
		</tr>
		<tr>
			<td>-</td>
			<td>Small cell</td>
			<td>3 (75%)</td>
			<td>1 (25%)</td>
			<td></td>
		</tr>
		<tr>
			<td>-</td>
			<td>Large cell</td>
			<td>1 (100%)</td>
			<td>0</td>
			<td></td>
		</tr>
		<tr>
			<td>2</td>
			<td>Concurrent systemic Rx</td>
			<td></td>
			<td></td>
			<td>1</td>
		</tr>
		<tr>
			<td>-</td>
			<td>Chemo</td>
			<td>5 (63%)</td>
			<td>3 (37%)</td>
			<td></td>
		</tr>
		<tr>
			<td>-</td>
			<td>Radiation</td>
			<td>2 (100%)</td>
			<td>0</td>
			<td></td>
		</tr>
		<tr>
			<td>-</td>
			<td>None</td>
			<td>17 (68%)</td>
			<td>8 (32%)</td>
			<td></td>
		</tr>
		<tr>
			<td>3</td>
			<td>Size of lesion</td>
			<td></td>
			<td></td>
			<td>0.066</td>
		</tr>
		<tr>
			<td>-</td>
			<td>&#60;=1cm</td>
			<td>8 (89%)</td>
			<td>1 (11%)</td>
			<td></td>
		</tr>
		<tr>
			<td>-</td>
			<td>1.1-2 cm</td>
			<td>10 (83%)</td>
			<td>2 (17%)</td>
			<td></td>
		</tr>
		<tr>
			<td>-</td>
			<td>2.1-3 cm</td>
			<td>3 (43%)</td>
			<td>4 (57%)</td>
			<td></td>
		</tr>
		<tr>
			<td>-</td>
			<td>&#62;3 cm</td>
			<td>3 (43%)</td>
			<td>4 (57%)</td>
			<td></td>
		</tr>
		<tr>
			<td colspan="5">Table 1: Response to ITC with cisplatin based on histology, concurrent systemic therapy and size</td>
		</tr>
	</tbody>
</table>
Table 1: Sub-group Analyses of Response to Cisplatin Based on a Few Select Variables. There was no statistically-significant difference in patient response based on tumor histology, size, or concurrent systemic therapy.

Watch this Scientific Journal Video about Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer at JoVE.com

Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer

The management of isolated recurrent lung cancer in a previously-irradiated field is challenging. Here, we describe an endobronchial ultrasound (EBUS)-guided cisplatin injection for the management of patients with localized lung cancer recurrence in a previously-radiated field.

Isolated hilar and mediastinal recurrence (IMHR) following external beam radiation therapy (EBRT) in patients with lung cancer is common. These patients ...

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Nanyang Technological University

Research

JoVE Journal

Cancer Research

10.4K Views.  University of Florida College of Medicine. The management of isolated recurrent lung cancer in a previously-irradiated field is challenging. Here, we describe an endobronchial ultrasound (EBUS)-guided cisplatin injection for the management of patients with localized lung cancer recurrence in a previously-radiated field. 

Video: Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer

Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression

The use of mouse models is indispensable for studying the pathophysiology of various diseases. With respect to lung cancer, several models are available, including genetically engineered models as well as transplantation models. However, genetically engineered mouse models are time-consuming and expensive, whereas some orthotopic transplantation models are difficult to reproduce. Here, a non-invasive intratracheal delivery method of lung tumor cells as an alternative orthotopic transplantation model is described. The use of mouse lung adenocarcinoma cells and syngeneic graft recipients allows studying tumorigenesis under the presence of a fully active immune system. Furthermore, genetic manipulations of tumor cells before transplantation makes this model an attractive time-saving approach to study the impact of genetic factors on tumor growth and tumor cell gene expression profiles under physiological conditions. Using this model, we show that lung adenocarcinoma cells express increased levels of the T-cell suppressor programmed death-ligand 1 (PD-L1) when grown in their natural environment as compared to cultivation in vitro.

Here we describe a minimally invasive syngeneic orthotopic transplantation model of mouse lung adenocarcinoma cells as a time- and cost-reducing model to study non-small cell lung cancer.

The use of mouse models is indispensable for studying the pathophysiology of various diseases. With respect to lung cancer, several models are available, ...

Substernal Thyroid Biopsy Using Endobronchial Ultrasound-guided Transbronchial Needle Aspiration

Substernal thyroid goiter (STG) represents about 5.8% of all mediastinal lesions1. There is a wide variation in the published incidence rates due to the lack of a standardized definition for STG. Biopsy is often required to differentiate benign from malignant lesions. Unlike cervical thyroid, the overlying sternum precludes ultrasound-guided percutaneous fine needle aspiration of STG. Consequently, surgical mediastinoscopy is performed in the majority of cases, causing significant procedure related morbidity and cost to healthcare. Endobronchial Ultrasound-guided Transbronchial Needle Aspiration (EBUS-TBNA) is a frequently used procedure for diagnosis and staging of non-small cell lung cancer (NSCLC). Minimally invasive needle biopsy for lesions adjacent to the airways can be performed under real-time ultrasound guidance using EBUS. Its safety and efficacy is well established with over 90% sensitivity and specificity. The ability to perform EBUS as an outpatient procedure with same-day discharges offers distinct morbidity and financial advantages over surgery. As physicians performing EBUS gained procedural expertise, they have attempted to diversify its role in the diagnosis of non-lymph node thoracic pathologies. We propose here a role for EBUS-TBNA in the diagnosis of substernal thyroid lesions, along with a step-by-step protocol for the procedure.

Substernal thyroid lesions are common, and need to be differentiated from malignancy. Obtaining percutaneous fine needle biopsy is not possible due to its retrosternal location. This article proposes a protocol for biopsy of substernal thyroid lesions using Endobronchial Ultrasound-guided Transbronchial Needle Aspiration (EBUS-TBNA).

Substernal thyroid goiter (STG) represents about 5.8% of all mediastinal lesions1. There is a wide variation in the published incidence rates due to the ...

Medicine

Intubation-mediated Intratracheal (IMIT) Instillation: A Noninvasive, Lung-specific Delivery System

Respiratory disease studies typically involve the use of murine models as surrogate systems. However, there are significant physiologic differences between the murine and human respiratory systems, especially in their upper respiratory tracts (URT). In some models, these differences in the murine nasal cavity can have a significant impact on disease progression and presentation in the lower respiratory tract (LRT) when using intranasal instillation techniques, potentially limiting the usefulness of the mouse model to study these diseases. For these reasons, it would be advantageous to develop a technique to instill bacteria directly into the mouse lungs in order to study LRT disease in the absence of involvement of the URT. We have termed this lung specific delivery technique intubation-mediated intratracheal (IMIT) instillation. This noninvasive technique minimizes the potential for instillation into the bloodstream, which can occur during more invasive traditional surgical intratracheal infection approaches, and limits the possibility of incidental digestive tract delivery. IMIT is a two-step process in which mice are first intubated, with an intermediate step to ensure correct catheter placement into the trachea, followed by insertion of a blunt needle into the catheter to mediate direct delivery of bacteria into the lung. This approach facilitates a &#62;98% efficacy of delivery into the lungs with excellent distribution of reagent throughout the lung. Thus, IMIT represents a novel approach to study LRT disease and therapeutic delivery directly into the lung, improving upon the ability to use mice as surrogates to study human respiratory disease. Furthermore, the accuracy and reproducibility of this delivery system also makes it amenable to Good Laboratory Practice Standards (GLPS), as well as delivery of a wide range of reagents which require high efficiency delivery to the lung.

Intubation-mediated Intratracheal IMIT Instillation: A Noninvasive, Lung-specific Delivery System

Intubation-mediated intratracheal (IMIT) instillation of reagents is an excellent, noninvasive method for studying respiratory disease, as well as a method for instilling therapeutic reagents directly into the lung. It is a rapid and highly reproducible method which is suitable for preclinical testing.

Respiratory disease studies typically involve the use of murine models as surrogate systems. However, there are significant physiologic differences ...

Intrapulmonary Inoculation of Multicellular Spheroids to Model Orthotopic NSCLC

Construction of An Orthotopic Xenograft Model of Non-Small Cell Lung Cancer Mimicking Disease Progression and Predicting Drug Activities

Non-small cell lung cancer (NSCLC) is a highly lethal disease with a complex and heterogeneous tumor microenvironment. Currently, common animal models based on subcutaneous inoculation of cancer cell suspensions do not recapitulate the tumor microenvironment in NSCLC. Herein we describe a murine orthotopic lung cancer xenograft model that employs the intrapulmonary inoculation of three-dimensional multicellular spheroids (MCS). Specifically, fluorescent human NSCLC cells (A549-iRFP) were cultured in low-attachment 96-well microplates with collagen for 3 weeks to form MCS, which were then inoculated intercostally into the left lung of athymic nude mice to establish the orthotopic lung cancer model.
Compared with the original A549 cell line, MCS of the A549-iRFP cell line responded similarly to anticancer drugs. The long-wavelength fluorescent signal of the A549-iRFP cells correlated strongly with common markers of cancer cell growth, including spheroid volume, cell viability, and cellular protein level, thus allowing dynamic monitoring of the cancer growth in vivo by fluorescent imaging. After inoculation into mice, the A549-iRFP MCS xenograft reliably progressed through phases closely resembling the clinical stages of NSCLC, including the expansion of the primary tumor, the emergence of neighboring secondary tumors, and the metastases of cancer cells to the contralateral right lung and remote organs. Moreover, the model responded to the benchmark antilung cancer drug, cisplatin with the anticipated toxicity and slower cancer progression. Therefore, this murine orthotopic xenograft model of NSCLC would serve as a platform to recapitulate the disease&#39;s progression and facilitate the development of potential anticancer drugs.

Author Spotlight: Establishing a Murine Non-Small Cell Lung Cancer Model for Developing Nanoformulations of Anticancer Drugs

This study presents an orthotopic non-small cell lung cancer (NSCLC) model based on intrapulmonary inoculation of multicellular spheroids of fluorescent A549-iRFP cells. The model recapitulates clinical NSCLC stages and responds to cisplatin, according to dynamic in vivo monitoring of long-wavelength fluorescence.

Non-small cell lung cancer (NSCLC) is a highly lethal disease with a complex and heterogeneous tumor microenvironment. Currently, common animal models ...

Dynamic Lung Tumor Tracking for Stereotactic Ablative Body Radiation Therapy

Physicians considering stereotactic ablative body radiation therapy (SBRT) for the treatment of extracranial cancer targets must be aware of the sizeable risks for normal tissue injury and the hazards of physical tumor miss. A first-of-its-kind SBRT platform achieves high-precision ablative radiation treatment through a combination of versatile real-time imaging solutions and sophisticated tumor tracking capabilities. It uses dual-diagnostic kV x-ray units for stereoscopic open-loop feedback of cancer target intrafraction movement occurring as a consequence of respiratory motions and heartbeat. Image-guided feedback drives a gimbaled radiation accelerator (maximum 15 x 15 cm field size) capable of real-time &#177;4 cm pan-and-tilt action. Robot-driven &#177;60&#176; pivots of an integrated &#177;185&#176; rotational gantry allow for coplanar and non-coplanar accelerator beam set-up angles, ultimately permitting unique treatment degrees of freedom. State-of-the-art software aids real-time six dimensional positioning, ensuring irradiation of cancer targets with sub-millimeter accuracy (0.4 mm at isocenter). Use of these features enables treating physicians to steer radiation dose to cancer tumor targets while simultaneously reducing radiation dose to normal tissues. By adding respiration correlated computed tomography (CT) and 2-[18F] fluoro-2-deoxy-&#7429;-glucose (18F-FDG) positron emission tomography (PET) images into the planning system for enhanced tumor target contouring, the likelihood of physical tumor miss becomes substantially less1. In this article, we describe new radiation plans for the treatment of moving lung tumors.

Stereotactic ablative body radiation therapy (SBRT) involves the precise delivery of high-dose radiation to cancer tumor targets. A novel SBRT platform offers a first-of-its-kind gimbaled radiation accelerator mounted within a pivoting O-ring gantry capable of dynamic image-guided tumor tracking. Here, we describe dynamic tumor tracking for lung targets.

Physicians considering stereotactic ablative body radiation therapy (SBRT) for the treatment of extracranial cancer targets must be aware of the sizeable ...

Treatment of Liver Metastases Using an Internal Target Volume Method for Stereotactic Body Radiotherapy

The prognosis of patients with metastatic cancers has improved in the past decades due to effective chemotherapy and oligometastatic surgery. For inoperable patients, local ablation therapies, such as stereotactic body radiotherapy (SBRT), can provide effective local tumor control with minimal toxicity. Because of its high precision and accuracy, SBRT delivers a higher radiation dose per fraction, is more effective, and targets smaller irradiation volumes than does conventional radiotherapy. In addition, steep dose gradients from target lesions to surrounding normal tissues are achieved using SBRT; thus, SBRT provides more effective tumor control and exhibits fewer side effects than conventional radiotherapy. The use of SBRT is prevalent for treating intracranial lesions (known as stereotactic radiosurgery); however, it is now also used for treating spinal and adrenal metastases. Because of advancements in image-guided assistance and respiratory motion management, several studies have investigated the use of SBRT for treating lung or liver tumors, which move as a patient breathes. The results of these studies have suggested that SBRT favorably controls tumors in the case of moving lesions.
Four-dimensional computed tomography (4D-CT) with an abdominal compressor (AC) is clinically convenient for effective respiratory motion management. Because this method is noninvasive and allows free breathing, its use reduces complications. Furthermore, patients consider this method convenient. Moreover, it is considered more efficient than other methods of respiratory motion management by physicians and therapists. The use of 4D-CT with an AC for treating pulmonary lesions has also been widely investigated, and the technique is gaining acceptance for treating hepatic lesions. However, the protocols for using 4D-CT with an AC for treating hepatic lesions are different from those used for treating pulmonary lesions. In this article, we describe a new protocol for SBRT with 4D-CT and an AC for treating liver metastases.

Stereotactic body radiotherapy (SBRT) requires rigorous accuracy and precision for delivering high radiation doses per fraction to small treatment volumes to improve tumor control and simultaneously reduce toxicity. Herein, we present a noninvasive and clinically convenient respiratory motion management protocol for SBRT for liver metastases.

The prognosis of patients with metastatic cancers has improved in the past decades due to effective chemotherapy and oligometastatic surgery. For ...

Direct Intrabronchial Administration to Improve the Selective Agent Deposition Within the Mouse Lung

Intratracheal (IT) administration of experimental agents is an essential technique in murine models of diffuse lung diseases, such as bleomycin-induced pulmonary fibrosis.&#160; However, distribution of intratracheally-administered agents to the distal mouse lung is often asymmetric, with lung parenchymal concentrations increased in the smaller (but equally accessible) left lung of the mouse.&#160; Described in this report is a novel intrabronchial (IB) approach to cannulate the left and/or right lungs of living mice non-operatively.&#160; It is also demonstrated how this approach can be used to selectively administer agents to one lung or adapted (via dose-adjusted IB delivery) to improve the left-right symmetry of lung delivery of experimental agents, thereby improving models of diffuse lung disease such as bleomycin-induced pulmonary fibrosis.

Intratracheal (IT) administration of experimental agents in mice often results in asymmetric delivery to the distal lungs.&#160; In this report, we describe a direct intrabronchial (IB) approach to cannulate each lung in living mice non-operatively.&#160; This approach can be used to selectively administer agents to one lung or may be adapted to improve the symmetric agent delivery to both lungs.

Intratracheal (IT) administration of experimental agents is an essential technique in murine models of diffuse lung diseases, such as bleomycin-induced ...

A Stepwise Approach for Performing Ultrasound Guided Transthoracic Lung Biopsy

Diagnosing patients with radiological lung lesions, especially those suspected of having primary lung cancer, is a common and critical clinical scenario. When selecting the most suitable invasive procedure to establish a diagnosis in these cases, a delicate balance must be struck between achieving a high diagnostic yield, providing staging information, minimizing potential complications, enhancing the patient experience, and controlling costs. The integration of thoracic ultrasound as a routine clinical tool in respiratory medicine has led to increased awareness and utilization of ultrasound-guided invasive techniques in chest procedures, including transthoracic biopsies. By following a systematic and stepwise approach, transthoracic ultrasound-guided lung biopsy emerges as a safe, cost-effective procedure with a remarkable diagnostic accuracy. These attributes collectively position it as an ideal invasive technique when technically feasible. Consequently, in patients presenting subpleural lung lesions suspected of malignancy, transthoracic ultrasound-guided lung biopsy has become a standard procedure in the realm of modern invasive pulmonology.

Transthoracic ultrasound-guided lung biopsy represents a safe, cost-effective, and efficient approach for patients presenting with subpleural lung lesions suspected of malignancy. Employing a systematic, step-by-step process is crucial to achieve optimal patient selection, minimize complication risks, and maximize diagnostic accuracy.

Diagnosing patients with radiological lung lesions, especially those suspected of having primary lung cancer, is a common and critical clinical scenario. ...

Advancements in Pulmonary Lesion Biopsy Through Robotic Bronchoscopy

Robotic-assisted Bronchoscopy Combined with Multimodal Imaging for Targeted Lung Cryobiopsies

Robotic-assisted bronchoscopy (RAB) allows for targeted bronchoscopic biopsy in the lung. A robotic-assisted bronchoscope is navigated through the airways under direct vision after establishing a pathway to a target lesion based on mapping performed on a 3-dimensional (3D) lung and airway reconstruction obtained from a pre-procedure thin-slice computed tomography chest. RAB has maneuverability to distal airways throughout the lung, precise catheter tip articulation, and stability with the robotic arm. Adjunct imaging tools such as fluoroscopy, radial endobronchial ultrasound (r-EBUS), and cone beam computed tomography (CBCT) can be used with RAB. Studies using shape-sensing robotic-assisted bronchoscopy (ssRAB) have shown favorable diagnostic outcomes and safety profiles in both malignant and non-malignant processes for the biopsy of peripheral pulmonary lesions (PPLs). A 1.1 mm cryoprobe combined with ssRAB has been shown to be safe and effective for the diagnosis of PPLs compared to a traditional bronchoscopy with forceps biopsy. This technique can also be used for targeted lung sampling in benign processes. The aim of this article is to describe a stepwise approach to performing RAB combined with fluoroscopy, r-EBUS, and CBCT to obtain targeted transbronchial lung cryobiopsies (TBLC).

Author Spotlight: Expanding Interventional Pulmonology Research with Robotic-Assisted Bronchoscopy

This article aims to describe a stepwise approach to performing robotic-assisted bronchoscopy combined with fluoroscopy, radial endobronchial ultrasound, and cone beam computed tomography to obtain targeted transbronchial lung cryobiopsies.&#160;

Robotic-assisted bronchoscopy (RAB) allows for targeted bronchoscopic biopsy in the lung. A robotic-assisted bronchoscope is navigated through the airways ...

A Near-Infrared Photoimmunotherapy Technique to Treat Lung Cancer in a Murine Model

Source: Yasui, H., et al. <a href="https://app-jove-com.remotexs.ntu.edu.sg/v/61593">Near Infrared Photoimmunotherapy for Mouse Models of Pleural Dissemination.</a> J. Vis. Exp. (2021)
This video demonstrates a near-infrared photoimmunotherapy technique to treat lung cancer in an engineered mouse model exhibiting luciferase-expressing tumor cells. Upon injecting an antibody-photosensitizer conjugate (APC) that binds to specific antigens on the tumor cells, the mouse is exposed to near-infrared radiation, inducing photochemical changes in the APC and leading to necrotic death of the bound tumor cells. The effectiveness of the treatment is monitored by injecting luciferin, a luciferase substrate, and measuring the bioluminescence over time, correlating with tumor growth.

Technika fotoimmunoterapii w bliskiej podczerwieni w leczeniu raka płuc w modelu mysim

All procedures involving animal models have been reviewed by the local institutional animal care committee and the JoVE veterinary review board.
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