This research was supported by Taipei Medical University Hospital (106TMUH-NE-02).

Taipei Medical University Joint Institutional Review Board approval was obtained for this study.
1. SBRT Consultation
<ol>
	<li>Assess patient eligibility for SBRT for the treatment of liver metastases by consulting a multidisciplinary tumor board. 
	NOTE: The need for local ablation as well as operation and other treatment options must be evaluated by the tumor board. Our selection criteria were as follows: 1) adult patients with a good performance status (Eastern Cooperative Oncology Group 0-1), 2) controlled cancer status through anticancer medication and with only oligometastases in the liver, 3) number of hepatic lesions &#8804;3 and largest tumor &#8804;6 cm in diameter, 4) liver volume (liver excluding gross tumor) greater than 700 cm3, and 5) without acute hepatitis or chronic hepatitis B under stable antiviral control.</li>
	<li>Discuss SBRT and its associated risks as well as the differences between SBRT and conventional radiotherapy with the patient9,19.</li>
</ol>
2. CT Simulation
<ol>
	<li>Place the patient in a supine position, head-first on the couch with arms over the head.
	<ol>
		<li>Use a system (e.g., BodyFIX) to immobilize the patient. Position the patient in a personalized, evacuated vacuum bag and cover the patient with a cover sheet.</li>
		<li>Apply an abdominal compressor (AC), and mark the depth of the AC. 
		NOTE: The AC restricts the patient&#39;s breathing motion; therefore, some patients may develop dyspnea during this procedure. Oxygen supplementation through the nasal cannula should be provided to relieve their discomfort.</li>
		<li>Place the breath-tracking sensor on the chest wall and monitor the respiratory waveform.</li>
	</ol>
	</li>
	<li>Acquire CT images for radiotherapy treatment planning.
	<ol>
		<li>Choose 4D-CT scan mode with a 3 mm slice thickness.</li>
		<li>Conduct a surview scan (120 kV, 30 mA) to obtain both anterior-posterior (AP) and lateral view of the patient. Click on &#34;Go&#34; on both the screen and the control panel.</li>
		<li>Determine the CT scanning coverage under &#34;Helical scan&#34; pagination and decide the scanning field of 4D-CT under &#34;Pulmonary gating scan&#34; pagination. 
		NOTE: The coverage of the helical scan should extend from the apex of both the lungs to a distance of at least 5 cm from the caudal border of the liver. The field of pulmonary gating scan, which is smaller than helical scan, should cover the liver with a 3-5 cm extend from both cranial and caudal borders of the liver.</li>
		<li>Monitor the respiratory waveform until it remains stable for 3 min.</li>
		<li>Inject 100 mL of contrast agent (e.g., Omnipaque), at a rate of 4-5 mL/s, through an 18 G i.v. catheter into antecubital vein.</li>
		<li>Conduct a contrasted contiguous helical CT scan (120 kV, 400 mAs/slice), 15 s after the contrast injection.</li>
		<li>Subsequently conduct a non-contrasted 4D-CT scan (120 kV, 2,000 mAs/slice) by clicking &#34;Next Series&#34;.</li>
	</ol>
	</li>
</ol>
3. Radiotherapy Treatment Planning
<ol>
	<li>Import images from the CT simulation and diagnostic scans into the planning system. 
	NOTE: Diagnostic images may include positron emission tomography (PET)/PET-CT, magnetic resonance image, or diagnostic helical CT scans.</li>
	<li>Contour metastatic tumors into gross tumor volume and adjacent organs at risk (OARs).
	<ol>
		<li>Choose an organ (here, the stomach) and use the brush, pencil, etc. to contour the organ in each slice of the CT image. Circle or define the organ of interest. Use &#34;Up&#34; and &#34;Down&#34; buttons to view each image slice. 
		NOTE: The OARs include the lungs, stomach, duodenum, spinal cord, liver, small bowel, ribs, and kidneys.</li>
	</ol>
	</li>
	<li>Contour the internal target volume (ITV) of the tumors according to organ motion observed on dynamic tracking images. Add a 5-mm margin to the ITV to obtain the planning target volume (PTV).
	<ol>
		<li>Choose an organ (here, the stomach) and use the brush, pencil, etc. to contour the organ in each slice of the CT image. Circle or define the organ of interest. Use &#34;Up&#34; and &#34;Down&#34; buttons to view each image slice.</li>
	</ol>
	</li>
	<li>Prescribe radiation doses of 48 Gy in three fractions or 35 Gy in five fractions to the PTV for relatively large tumors. 
	NOTE: A treatment plan must consider constraints due to the OARs; a relatively high prescription dose may be acceptable if the radiation dose to the OARs is within the constraints (Table 1).</li>
</ol>
4. Treatment Delivery
<ol>
	<li>Reconfirm the radiation beam data by using daily quality assurance and ensure that the data are within the normal range.</li>
	<li>Identify the patient using the patient&#39;s name, birth date, and ID card. Position the patient in the vacuum bag, place the cover sheet, and fix the AC according to the procedure described in the CT simulation section.</li>
	<li>Acquire a 4D cone-beam CT (CBCT) image and adjust the couch to correlate the target location obtained on the 4D-CBCT image to that obtained on the simulation CT images.
	<ol>
		<li>Select 4D CBCT mode and confirm setup data. Click &#34;Go&#34; on the panel.</li>
	</ol>
	</li>
	<li>After 4D CBCT, load the acquired 4D CBCT images into the IGRT system. The upper left and lower right images are from CT simulation as the contouring and treatment planning. The upper right and lower left images are from 4D CBCT, which is performed daily before each fraction.
	<ol>
		<li>Use the software to adjust the set up. Then, manually adjust each parameter on the couch. The couch has only 3 linear motions in X, Y, and Z axes while the system could have adjustment in 6, including rotation, pitch and roll. Therefore, the technicians need to corroborate the adjustment.</li>
		<li>Record and print out the parameters for daily adjustment. 
		NOTE: If the tumor position shifts beyond the tolerance limit of 5 mm on any one of six axes, the patient should be repositioned.</li>
	</ol>
	</li>
	<li>Deliver radiation treatment. Confirm treatment plan and the system configuration. Click Go to start the treatment. Monitor the patient using real-time cameras during the entire treatment to ensure patient safety.</li>
</ol>

<ol>
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Rev Clin Oncol. 8 (6), 378-382 (2011).</li><li>Comito, T., Clerici, E., Tozzi, A., D'Agostino, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Liver+metastases+and+SBRT:+A+new+paradigm?.">Liver metastases and SBRT: A new paradigm?.</a> Rep Pract Oncol Radiother. 20 (6), 464-471 (2015).</li><li>Scorsetti, M., Clerici, E., Comito, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stereotactic+body+radiation+therapy+for+liver+metastases.">Stereotactic body radiation therapy for liver metastases.</a> J Gastrointest Oncol. 5 (3), 190-197 (2014).</li><li>Shady, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Percutaneous+Radiofrequency+Ablation+of+Colorectal+Cancer+Liver+Metastases:+Factors+Affecting+Outcomes--A+10-year+Experience+at+a+Single+Center.">Percutaneous Radiofrequency Ablation of Colorectal Cancer Liver Metastases: Factors Affecting Outcomes--A 10-year Experience at a Single Center.</a> Radiology. 278 (2), 601-611 (2016).</li><li>van Hazel, G. 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The authors have no disclosures.

Respiration-induced liver deformity and organ motion contribute to the difficulties associated with radiation delivery, as well as contouring (target delineation) problems. Improvements in the techniques used for organ motion management have led to improvements in treatment accuracy and precision, which is fundamental to SBRT. Several image-guided techniques and respiratory motion management systems are currently available. Fiducial marker implantation is a common technique for target localization. A fiducial marker is u...

Conventionally, metastasis is considered the terminal stage of cancer and is associated with poor prognosis and survival. However, Mountain et al. in 1984 reported that according to their 20-year experience, complete surgical removal of pulmonary metastasis results in a relatively higher survival rate if the primary tumor site is under systemic control at the time of surgery1. Hellman and Weichselbaum in 1995 first proposed oligometastases, an intermediate stage between localized lesions and systemic disease with polymetastases, which can be cured using additional local treatment2,3. Over the past decades, early detection of metastasis, novel surgical methods for treating oligometastases (metastasectomy), and effective chemotherapy have improved the prognosis in patients with metastasis. The liver is one of the most common metastatic organs for solid tumors, and surgical resection of hepatic oligometastases can improve survival. Local ablation methods, including radiofrequency ablation, radioembolization, and radiotherapy, for treating liver metastases have been recommended for some inoperable patients to achieve the necessary local tumor control3,4,5,6,7. In past years, several prospective and retrospective studies have reported effective local tumor control of hepatic metastases through stereotactic body radiotherapy (SBRT), also known as stereotactic ablative radiotherapy, with tolerable toxicity4,5,8,9.
Improvements have been made in patient positioning and immobilization methods; image acquisition, integration, and transfer to radiotherapy systems; respiratory motion management; high-dose output and fast radiation delivery; and steep dose gradients from target lesions to surrounding normal tissues. Because of these advances, SBRT achieves highly precise and accurate radiotherapy with minimal serious toxicity10,11. Respiratory motion management is fundamental to SBRT, particularly for hepatic and pulmonary lesions. A respiratory management technique that is noninvasive and clinically convenient would substantially increase the popularity of SBRT as a treatment option. This article details an SBRT protocol for liver metastases that uses four-dimensional computed tomography (4D-CT) with an abdominal compressor (AC) for image-guided assistance and liver motion management.

<table border="0" cellpadding="0" cellspacing="0" width="875">
	<tbody>
		<tr height="51">
			<td height="51" style="height:51px;width:195px;">CT scan</td>
			<td style="width:188px;">Philips</td>
			<td style="width:265px;">Brilliance&#160;Big Bore&#160;16 Slice&#160;CT, 7387</td>
			<td style="width:228px;">Acquire CT images for contouring and planning</td>
		</tr>
		<tr height="51">
			<td height="51" style="height:51px;width:195px;">CT contrast</td>
			<td style="width:188px;">GE Healthcare</td>
			<td style="width:265px;">Omnipaque 350 mg L/mL</td>
			<td style="width:228px;">Enhence lesion in CT images</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Linear accelerator</td>
			<td>Elekta</td>
			<td>Synergy</td>
			<td>Deliver radiotherapy</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Palnning system</td>
			<td>Pinnacle</td>
			<td>Pinnacle 9.8</td>
			<td>Implement radiotherapy planning</td>
		</tr>
		<tr height="65">
			<td height="65" style="height:65px;width:195px;">Immobilization: BlueBag BodyFix</td>
			<td>Elekta</td>
			<td>900 mm x 2325 mm, P10104840</td>
			<td>Immobilize the patient</td>
		</tr>
		<tr height="66">
			<td height="66" style="height:66px;width:195px;">Immobilization: BodyFix Cover sheet</td>
			<td>Elekta</td>
			<td>2700 mm x 1400 mm, P10102-304</td>
			<td>Immobilize the patient</td>
		</tr>
		<tr height="73">
			<td height="73" style="height:73px;width:195px;">Immobilization: BodyFix abdominal compressor</td>
			<td>Elekta</td>
			<td>diaphragm control, P10102-149</td>
			<td style="width:228px;">Restrict breath motion and organ/lesion motion</td>
		</tr>
		<tr height="57">
			<td height="57" style="height:57px;width:195px;">Immobilization: vacuum pump</td>
			<td>Elekta</td>
			<td>vacuum pump, p2 120V, P10102-110</td>
			<td style="width:228px;">Shape body bag and cover sheet according to the patient</td>
		</tr>
	</tbody>
</table>

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.

SBRT can be implemented by intense-modulated radiotherapy (IMRT) (with <img alt="image" src="/files/ftp_upload/57050/57050imgv2.jpg" /> 6 radiation beams) or volumetric arc radiotherapy (VMAT) (with continuous dose delivery and gantry rotation) to cover all targets in a single treatment because a single surgery may not achieve removal of all the tumors. A representative SBRT treatment plan demonstrated successful radiotherapy planning for two hepatic metastatic tumors when surgery was inf...

Watch this Scientific Journal Video about Treatment of Liver Metastases Using an Internal Target Volume Method for Stereotactic Body Radiotherapy at JoVE.com

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

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 ...

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14.0K Views.  Taipei Medical University Hospital. 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. 

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

Combination Radiotherapy in an Orthotopic Mouse Brain Tumor Model

Glioblastoma multiforme (GBM) are the most common and aggressive adult primary brain tumors1. In recent years there has been substantial progress in the understanding of the mechanics of tumor invasion, and direct intracerebral inoculation of tumor provides the opportunity of observing the invasive process in a physiologically appropriate environment2. As far as human brain tumors are concerned, the orthotopic models currently available are established either by stereotaxic injection of cell suspensions or implantation of a solid piece of tumor through a complicated craniotomy procedure3. In our technique we harvest cells from tissue culture to create a cell suspension used to implant directly into the brain. The duration of the surgery is approximately 30 minutes, and as the mouse needs to be in a constant surgical plane, an injectable anesthetic is used. The mouse is placed in a stereotaxic jig made by Stoetling (figure 1). After the surgical area is cleaned and prepared, an incision is made; and the bregma is located to determine the location of the craniotomy. The location of the craniotomy is 2 mm to the right and 1 mm rostral to the bregma. The depth is 3 mm from the surface of the skull, and cells are injected at a rate of 2 &mu;l every 2 minutes. The skin is sutured with 5-0 PDS, and the mouse is allowed to wake up on a heating pad. From our experience, depending on the cell line, treatment can take place from 7-10 days after surgery. Drug delivery is dependent on the drug composition. For radiation treatment the mice are anesthetized, and put into a custom made jig. Lead covers the mouse's body and exposes only the brain of the mouse. The study of tumorigenesis and the evaluation of new therapies for GBM require accurate and reproducible brain tumor animal models. Thus we use this orthotopic brain model to study the interaction of the microenvironment of the brain and the tumor, to test the effectiveness of different therapeutic agents with and without radiation.

The purpose of this article is to describe the use of an orthotopic glioblastoma model for chemoradiation studies. This article will go though cell processing, implanting, and radiotherapy of the mouse using an intracranial model.

Glioblastoma multiforme (GBM) are the most common and aggressive adult primary brain tumors1. In recent years there has been substantial progress in the ...

Stereotactic Radiosurgery for Gynecologic Cancer

Stereotactic body radiotherapy (SBRT) distinguishes itself by necessitating more rigid patient immobilization, accounting for respiratory motion, intricate treatment planning, on-board imaging, and reduced number of ablative radiation doses to cancer targets usually refractory to chemotherapy and conventional radiation. Steep SBRT radiation dose drop-off permits narrow 'pencil beam' treatment fields to be used for ablative radiation treatment condensed into 1 to 3 treatments.
Treating physicians must appreciate that SBRT comes at a bigger danger of normal tissue injury and chance of geographic tumor miss. Both must be tackled by immobilization of cancer targets and by high-precision treatment delivery. Cancer target immobilization has been achieved through use of indexed customized Styrofoam casts, evacuated bean bags, or body-fix molds with patient-independent abdominal compression.1-3 Intrafraction motion of cancer targets due to breathing now can be reduced by patient-responsive breath hold techniques,4 patient mouthpiece active breathing coordination,5 respiration-correlated computed tomography,6 or image-guided tracking of fiducials implanted within and around a moving tumor.7-9 The Cyberknife system (Accuray [Sunnyvale, CA]) utilizes a radiation linear accelerator mounted on a industrial robotic arm that accurately follows patient respiratory motion by a camera-tracked set of light-emitting diodes (LED) impregnated on a vest fitted to a patient.10 Substantial reductions in radiation therapy margins can be achieved by motion tracking, ultimately rendering a smaller planning target volumes that are irradiated with submillimeter accuracy.11-13
Cancer targets treated by SBRT are irradiated by converging, tightly collimated beams. Resultant radiation dose to cancer target volume histograms have a more pronounced radiation "shoulder" indicating high percentage target coverage and a small high-dose radiation "tail." Thus, increased target conformality comes at the expense of decreased dose uniformity in the SBRT cancer target. This may have implications for both subsequent tumor control in the SBRT target and normal tissue tolerance of organs at-risk. Due to the sharp dose falloff in SBRT, the possibility of occult disease escaping ablative radiation dose occurs when cancer targets are not fully recognized and inadequate SBRT dose margins are applied. Clinical target volume (CTV) expansion by 0.5 cm, resulting in a larger planning target volume (PTV), is associated with increased target control without undue normal tissue injury.7,8 Further reduction in the probability of geographic miss may be achieved by incorporation of 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET).8 Use of 18F-FDG PET/CT in SBRT treatment planning is only the beginning of attempts to discover new imaging target molecular signatures for gynecologic cancers.

Stereotactic body radiotherapy (SBRT) involves image-guided, ablative radiation delivered to cancer targets refractory to chemotherapy or to conventional radiation treatment. The robotic-armed Cyberknife SBRT system, using sophisticated target localization, delivers hypofractionated radiation doses capable of sterilizing cancer targets. This article will consider new therapeutic roles of SBRT for gynecological cancers.

Stereotactic body radiotherapy (SBRT) distinguishes itself by necessitating more rigid patient immobilization, accounting for respiratory motion, ...

Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics

The molecular analysis of established cancer cell lines has been the mainstay of cancer research for the past several decades. Cell culture provides both direct and rapid analysis of therapeutic sensitivity and resistance. However, recent evidence suggests that therapeutic response is not exclusive to the inherent molecular composition of cancer cells but rather is greatly influenced by the tumor cell microenvironment, a feature that cannot be recapitulated by traditional culturing methods. Even implementation of tumor xenografts, though providing a wealth of information on drug delivery/efficacy, cannot capture the tumor cell/microenvironment crosstalk (i.e., soluble factors) that occurs within human tumors and greatly impacts tumor response. To this extent, we have developed an ex vivo (fresh tissue sectioning) technique which allows for the direct assessment of treatment response for preclinical and clinical therapeutics development. This technique maintains tissue integrity and cellular architecture within the tumor cell/microenvironment context throughout treatment response providing a more precise means to assess drug efficacy.

Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics

Established cancer cell lines and xenografts have been the mainstay of cancer research for the past several decades. However, recent evidence suggests that therapeutic response is greatly influenced by the tumor cell microenvironment. Therefore, we have developed an ex vivo analysis of primary tumor specimens for drug development purposes.

The molecular analysis of established cancer cell lines has been the mainstay of cancer research for the past several decades. Cell culture provides both ...

Isolated Hepatic Perfusion as a Treatment for Liver Metastases of Uveal Melanoma

Isolated hepatic perfusion (IHP) is a procedure where the liver is surgically isolated and perfused with a high concentration of the chemotherapeutic agent melphalan. Briefly, the procedure starts with the setup of a percutaneous veno-venous bypass from the femoral vein to the external jugular vein. Via a laparotomy, catheters are then inserted into the proper hepatic artery and the caval vein. The portal vein and the caval vein, both supra- and infrahepatically, are then clamped. The arterial and venous catheters are connected to a heart lung machine and the liver is perfused with melphalan (1 mg/kg body weight) for 60 min. This way it is possible to locally perfuse the liver with a high dose of a chemotherapeutic agent, without leakage to the systemic circulation.
In previous studies including patients with isolated liver metastases of uveal melanoma, an overall response rate of 33-100% and a median survival between 9 and 13 months, have been reported. The aim of this protocol is to give a clear description of how to perform the procedure and to discuss IHP as a treatment option for liver metastases of uveal melanoma.

Here, we present a protocol how to perform an isolated liver perfusion (IHP) with melphalan and we also discuss IHP as a treatment option for liver metastases of uveal melanoma.

Isolated hepatic perfusion (IHP) is a procedure where the liver is surgically isolated and perfused with a high concentration of the chemotherapeutic ...

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 ...

An Improved Method for Rapid Intubation of the Trachea in Mice

Despite some anatomical and physiological differences, mouse models continue to be an essential tool for studying human lung disease. Bleomycin toxicity is a commonly used model to study both acute lung injury and fibrosis, and multiple methods have been developed for administering bleomycin (and other toxic agents) into the lungs. However, many of these approaches, such as transtracheal instillation, have inherent drawbacks, including the need for strong anesthetics and survival surgery. This paper reports a quick, reproducible method of intratracheal intubation that involves mild inhaled anesthesia, visualization of the trachea, and the use of a surrogate spirometer to confirm exposure. As a proof of concept, 8-12 week old C57BL/6 mice were administered either 2.0 U/kg of bleomycin or an equivalent volume of PBS, and both damage and fibrotic endpoints were measured post-exposure. This procedure allows researchers to treat a large cohort of mice in a relatively short period with little expense and minimal post-procedure care.

This article presents a rapid and simple method for administering bleomycin directly into the mouse trachea via intubation. Key advantages of this method are that it is highly reproducible, easy to master, and does not require specialized equipment or lengthy recovery times.

Despite some anatomical and physiological differences, mouse models continue to be an essential tool for studying human lung disease. Bleomycin toxicity ...

Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver

Unresectable liver metastases of colorectal cancer can be treated with systemic chemotherapy, aiming to limit the disease, extend survival or turn unresectable metastases into resectable ones. Some patients however, suffer from side effects or progression under systemic treatment. For patients with metastasized uveal melanoma there are no standard systemic therapy options. For patients without extrahepatic disease, isolated liver perfusion (IHP) may enable local disease control with limited systemic side effects. Previously, this was performed during open surgery with satisfying results, but morbidity and mortality related to the open procedure, prohibited a widespread application. Therefore, percutaneous hepatic perfusion (PHP) with simultaneous chemofiltration was developed. Besides decreasing morbidity and mortality, this procedure can be repeated, hopefully leading to a higher response rate and improved survival (by local control of disease). During PHP, catheters are placed in the proper hepatic artery, to infuse the chemotherapeutic agent, and in the inferior caval vein to aspirate the chemosaturated blood returning through the hepatic veins. The caval vein catheter is a double balloon catheter that prohibits leakage into the systemic circulation. The blood returning from the hepatic veins is aspirated through the catheter fenestrations and then perfused through an extra-corporeal filtration system. After filtration, the blood is returned to the patient by a third catheter in the right internal jugular vein. During PHP a high dose of melphalan is infused into the liver, which is toxic and would lead to life threatening complications when administered systemically. Because of the significant hemodynamic instability resulting from the combination of caval vein occlusion and chemofiltration, hemodynamic monitoring and hemodynamic support is of paramount importance during this complex procedure.

Percutaneous Hepatic Perfusion PHP with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver

In this manuscript, we describe percutaneous isolated hepatic perfusion with simultaneous chemofiltration as treatment for unresectable liver metastases. This procedure is performed under general anaesthesia in the angiosuite by an experienced team, consisting of an interventional radiologist, a clinical perfusionist and anaesthesiologist.

Unresectable liver metastases of colorectal cancer can be treated with systemic chemotherapy, aiming to limit the disease, extend survival or turn ...

Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model

Major hepatic surgery with inflow occlusion, and liver transplantation, necessitate a period of warm ischemia, and a period of reperfusion leading to ischemia/reperfusion (I/R) injury with myriad negative consequences. Potential I/R injury in marginal organs destined for liver transplantation contributes to the current donor shortage secondary to a decreased organ utilization rate. A significant need exists to explore hepatic I/R injury in order to mediate its impact on graft function in transplantation. Rat liver hilar clamp models are used to investigate the impact of different molecules on hepatic I/R injury. Depending on the model, these molecules have been delivered using inhalation, epidural infusion, intraperitoneal injection, intravenous administration or injection into the peripheral superior mesenteric vein. A rat liver hilar clamp model has been developed for use in studying the impact of pharmacologic molecules in ameliorating I/R injury. The described model for rat liver hilar clamp includes direct cannulation of the portal supply to the ischemic hepatic segment via a side branch of the portal vein, allowing for direct segmental hepatic delivery. Our approach is to induce ischemia in the left lateral and median lobes for 60 min, during which time the substance under study is infused. In this case, pegylated-superoxide dismutase (PEG-SOD), a free radical scavenger, is infused directly into the ischemic segment. This series of experiments demonstrates that infusion of PEG-SOD is protective against hepatic I/R injury. Advantages of this approach include direct injection of the molecule into the ischemic segment with consequent decrease in volume of distribution and reduction in systemic side effects.

A unique rat liver hilar clamp model was developed for studying the impact of pharmacologic molecules in ameliorating ischemia-reperfusion injury. This model includes direct cannulation of the portal supply to the ischemic liver segment via a branch of the portal vein, allowing for direct hepatic delivery.

Major hepatic surgery with inflow occlusion, and liver transplantation, necessitate a period of warm ischemia, and a period of reperfusion leading to ...

Radiation Planning Assistant - A Streamlined, Fully Automated Radiotherapy Treatment Planning System

The Radiation Planning Assistant (RPA) is a system developed for the fully automated creation of radiotherapy treatment plans, including volume-modulated arc therapy (VMAT) plans for patients with head/neck cancer and 4-field box plans for patients with cervical cancer. It is a combination of specially developed in-house software that uses an application programming interface to communicate with a commercial radiotherapy treatment planning system. It also interfaces with a commercial secondary dose verification software. The necessary inputs to the system are a Treatment Plan Order, approved by the radiation oncologist, and a simulation computed tomography (CT) image, approved by the radiographer. The RPA then generates a complete radiotherapy treatment plan. For the cervical cancer treatment plans, no additional user intervention is necessary until the plan is complete. For head/neck treatment plans, after the normal tissue and some of the target structures are automatically delineated on the CT image, the radiation oncologist must review the contours, making edits if necessary. They also delineate the gross tumor volume. The RPA then completes the treatment planning process, creating a VMAT plan. Finally, the completed plan must be reviewed by qualified clinical staff.

Radiation therapy is a highly complex cancer treatment that requires multiple specialists to create a treatment plan and provide quality assurance (QA) prior to delivery to a patient. This protocol describes the use of a fully automated system, the Radiation Planning Assistant (RPA), to create high-quality radiation treatment plans.

The Radiation Planning Assistant (RPA) is a system developed for the fully automated creation of radiotherapy treatment plans, including volume-modulated ...

Predicting Treatment Response to Image-Guided Therapies Using Machine Learning: An Example for Trans-Arterial Treatment of Hepatocellular Carcinoma

Intra-arterial therapies are the standard of care for patients with hepatocellular carcinoma who cannot undergo surgical resection. The objective of this study was to develop a method to predict response to intra-arterial treatment prior to intervention.
The method provides a general framework for predicting outcomes prior to intra-arterial therapy. It involves pooling clinical, demographic and imaging data across a cohort of patients and using these data to train a machine learning model. The trained model is applied to new patients in order to predict their likelihood of response to intra-arterial therapy.
The method entails the acquisition and parsing of clinical, demographic and imaging data from N patients who have already undergone trans-arterial therapies. These data are parsed into discrete features (age, sex, cirrhosis, degree of tumor enhancement, etc.) and binarized into true/false values (e.g., age over 60, male gender, tumor enhancement beyond a set threshold, etc.). Low-variance features and features with low univariate associations with the outcome are removed. Each treated patient is labeled according to whether they responded or did not respond to treatment. Each training patient is thus represented by a set of binary features and an outcome label. Machine learning models are trained using N - 1 patients with testing on the left-out patient. This process is repeated for each of the N patients. The N models are averaged to arrive at a final model.
The technique is extensible and enables inclusion of additional features in the future. It is also a generalizable process that may be applied to clinical research questions outside of interventional radiology. The main limitation is the need to derive features manually from each patient. A popular modern form of machine learning called deep learning does not suffer from this limitation, but requires larger datasets.

Intra-arterial therapies are the standard of care for patients with hepatocellular carcinoma who cannot undergo surgical resection. A method for predicting response to these therapies is proposed. The technique uses pre-procedural clinical, demographic, and imaging information to train machine learning models capable of predicting response prior to treatment.

Intra-arterial therapies are the standard of care for patients with hepatocellular carcinoma who cannot undergo surgical resection. The objective of this ...