Name: endobronchial ultrasound-guided intratumoral injection of cisplatin for the treatment of isolated mediastinal recurrence of lung cancer
Uploaded: 2017-02-12T14:00:00
Description: 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

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 recu...

<ol>
	<li>. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> International Agency for Research on Cancer. , (2012).</li><li>Siegel, R., Ma, J., Zou, Z., Jemal, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cancer+statistics,+2014.">Cancer statistics, 2014.</a> CA Cancer J Clin. 64 (1), 9-29 (2014).</li><li>Jeremic, B., Videtic, G. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chest+reirradiation+with+external+beam+radiotherapy+for+locally+recurrent+non-small-cell+lung+cancer:+a+review.">Chest reirradiation with external beam radiotherapy for locally recurrent non-small-cell lung cancer: a review.</a> Int J Radiat Oncol Biol Phys. 80 (4), 969-977 (2011).</li><li>Perez, C. A., 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=Impact+of+irradiation+technique+and+tumor+extent+in+tumor+control+and+survival+of+patients+with+unresectable+non-oat+cell+carcinoma+of+the+lung:+report+by+the+Radiation+Therapy+Oncology+Group.">Impact of irradiation technique and tumor extent in tumor control and survival of patients with unresectable non-oat cell carcinoma of the lung: report by the Radiation Therapy Oncology Group.</a> Cancer. 50 (6), 1091-1099 (1982).</li><li>Hainsworth, J. D., 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=Weekly+docetaxel+with+either+gemcitabine+or+vinorelbine+as+second-line+treatment+in+patients+with+advanced+nonsmall+cell+lung+carcinoma:+Phase+II+trials+of+the+Minnie+Pearl+Cancer+Research+Network.">Weekly docetaxel with either gemcitabine or vinorelbine as second-line treatment in patients with advanced nonsmall cell lung carcinoma: Phase II trials of the Minnie Pearl Cancer Research Network.</a> Cancer. 92 (9), 2391-2398 (2001).</li><li>Grossi, F., 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=Phase+II+study+of+irinotecan+and+docetaxel+in+patients+with+previously+treated+non-small+cell+lung+cancer:+an+Alpe-Adria+Thoracic+Oncology+Multidisciplinary+group+study+(ATOM+007).">Phase II study of irinotecan and docetaxel in patients with previously treated non-small cell lung cancer: an Alpe-Adria Thoracic Oncology Multidisciplinary group study (ATOM 007).</a> Lung Cancer. 52 (1), 89-92 (2006).</li><li>Celikoglu, F., Celikoglu, S. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intratumoural+chemotherapy+with+5-fluorouracil+for+palliation+of+bronchial+cancer+in+patients+with+severe+airway+obstruction.">Intratumoural chemotherapy with 5-fluorouracil for palliation of bronchial cancer in patients with severe airway obstruction.</a> J Pharm Pharmacol. 55 (10), 1441-1448 (2003).</li><li>Eisenhauer, E. A., 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=New+response+evaluation+criteria+in+solid+tumours:+revised+RECIST+guideline+(version+1.1).">New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).</a> Eur J Cancer. 45 (2), 228-247 (2009).</li><li>Celikoglu, F., Celikoglu, S. I., York, A. M., Goldberg, E. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intratumoral+administration+of+cisplatin+through+a+bronchoscope+followed+by+irradiation+for+treatment+of+inoperable+non-small+cell+obstructive+lung+cancer.">Intratumoral administration of cisplatin through a bronchoscope followed by irradiation for treatment of inoperable non-small cell obstructive lung cancer.</a> Lung Cancer. 51 (2), 225-236 (2006).</li><li>Celikoglu, S. I., Celikoglu, F., Goldberg, E. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Endobronchial+intratumoral+chemotherapy+(EITC)+followed+by+surgery+in+early+non-small+cell+lung+cancer+with+polypoid+growth+causing+erroneous+impression+of+advanced+disease.">Endobronchial intratumoral chemotherapy (EITC) followed by surgery in early non-small cell lung cancer with polypoid growth causing erroneous impression of advanced disease.</a> Lung Cancer. 54 (3), 339-346 (2006).</li><li>Kilburn, J. M., 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=Management+of+mediastinal+relapse+after+treatment+with+stereotactic+body+radiotherapy+or+accelerated+hypofractionated+radiotherapy+for+stage+I/II+non-small-cell+lung+cancer.">Management of mediastinal relapse after treatment with stereotactic body radiotherapy or accelerated hypofractionated radiotherapy for stage I/II non-small-cell lung cancer.</a> J Thorac Oncol. 9 (4), 572-576 (2014).</li><li>Goldberg, E. P., Hadba, A. R., Almond, B. A., Marotta, J. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intratumoral+cancer+chemotherapy+and+immunotherapy:+opportunities+for+nonsystemic+preoperative+drug+delivery.">Intratumoral cancer chemotherapy and immunotherapy: opportunities for nonsystemic preoperative drug delivery.</a> J Pharm Pharmacol. 54 (2), 159-180 (2002).</li><li>Sandler, A. B., 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=Phase+III+trial+of+gemcitabine+plus+cisplatin+versus+cisplatin+alone+in+patients+with+locally+advanced+or+metastatic+non-small-cell+lung+cancer.">Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer.</a> J Clin Oncol. 18 (1), 122-130 (2000).</li><li>Ciotti, R., 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=Prospective+evaluation+of+anthracycline-related+early+cardiac+damage:+how+do+we+monitor+it.">Prospective evaluation of anthracycline-related early cardiac damage: how do we monitor it.</a> J Clin Oncol. 19 (22), 4269-4270 (2001).</li><li>Burris, H. A., 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=Intratumoral+cisplatin/epinephrine-injectable+gel+as+a+palliative+treatment+for+accessible+solid+tumors:+a+multicenter+pilot+study.">Intratumoral cisplatin/epinephrine-injectable gel as a palliative treatment for accessible solid tumors: a multicenter pilot study.</a> Otolaryngol Head Neck Surg. 118 (4), 496-503 (1998).</li><li>Vogl, T. J., 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=CT-guided+intratumoural+administration+of+cisplatin/epinephrine+gel+for+treatment+of+malignant+liver+tumours.">CT-guided intratumoural administration of cisplatin/epinephrine gel for treatment of malignant liver tumours.</a> Br J Cancer. 86 (4), 524-529 (2002).</li><li>Monga, S. P., 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=Endoscopic+treatment+of+gastric+cancer+with+intratumoral+cisplatin/epinephrine+injectable+gel:+a+case+report.">Endoscopic treatment of gastric cancer with intratumoral cisplatin/epinephrine injectable gel: a case report.</a> Gastrointest Endosc. 48 (4), 415-417 (1998).</li><li>Monga, S. P., 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=Intratumoral+therapy+of+cisplatin/epinephrine+injectable+gel+for+palliation+in+patients+with+obstructive+esophageal+cancer.">Intratumoral therapy of cisplatin/epinephrine injectable gel for palliation in patients with obstructive esophageal cancer.</a> Am J Clin Oncol. 23 (4), 386-392 (2000).</li><li>Shepherd, F. A., 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=Prospective+randomized+trial+of+docetaxel+versus+best+supportive+care+in+patients+with+non-small-cell+lung+cancer+previously+treated+with+platinum-based+chemotherapy.">Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy.</a> J Clin Oncol. 18 (10), 2095-2103 (2000).</li><li>Hanna, N., 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=Randomized+phase+III+trial+of+pemetrexed+versus+docetaxel+in+patients+with+non-small-cell+lung+cancer+previously+treated+with+chemotherapy.">Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy.</a> J Clin Oncol. 22 (9), 1589-1597 (2004).</li></ol>

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.
Ther...

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 border="0" cellpadding="0" cellspacing="0" width="261">
	<tbody>
		<tr height="20">
			<td colspan="2" height="20" style="height:20px;width:261px;">Bronchoscope</td>
		</tr>
		<tr height="20">
			<td colspan="2" height="20" style="height:20px;">22 Guage olympus EBUS needle</td>
		</tr>
		<tr height="20">
			<td colspan="2" height="20" style="height:20px;">40 g of cisplatin in 40 mls of normal saline</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 ...

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 ...

The overall goal of this procedure is to describe an endobronchial ultrasound or EBUS-guided cisplatin injection for the management of patients with localized lung cancer recurrence in a previously radiated field. This method can help answer key questions in the field of lung cancer treatment about the safety and efficacy of EBUS-guided trans-bronchial intratumoral injection of cisplatin for recurrence of lung cancers in the post-radiated field. The main advantage of this technique is that it provides an alternative treatment option to systemic chemotherapy for patients with isolated, hilar, and mediastinal recurrence of lung cancer.For real-time visualization of hilar, mediastinal, and peribronchial structures for intratumoral cisplatin injection, first intravenously administer dexamethasone and ondansetron to a patient who has abstained from oral food and fluids for at least six hours. Next, induce conscious sedation with intravenous Midazolam and Fentanyl treatment, coupled with the topical application of five milliliters of Lidocaine. Use standard monitoring, including a continuous 3-lead electrocardiogram for heart rate monitoring, continuous pulse oximetry, and respiratory rate measurements.Now locate the target lesion using a convex probe EBUS with a built-in ultrasound probe on a flexible bronchoscope to advance the scope through the vocal cords. When the scope reaches the airways, turn on the EBUS processor and use one to two milliliters of normal saline to inflate the balloon at the tip of the scope. Flex the scope across the airway wall to locate the lesion.Then deploy the 22-gauge EBUS needle through the working channel of the scope and lock the needle into position. Under real-time ultrasound guidance, puncture the tracheobronchial wall and insert the needle into the target lesion. Remove the stylet within the needle and inject 10 milliliters of cisplatin into the lesion.Then retract the needle back into the sheath and inject the needle into a separate area of the lesion for the injection of another 10 milliliters of cisplatin. Remove the needle from the working channel of the scope and suction any additional drug from the distal airways. Then remove the bronchoscope.In this representative study, 8 to 12 weeks after therapy, 69%of the patients were classified as responders and 31%as non-responders, with a median survival of 8 months, 10 months for the responders, and six months for the non-responders, with a significantly higher progression-free survival rate observed in the responders group. While attempting this procedure, it is important to select appropriate patients, and to perform all of the steps in the protocol in a systematic manner. After its development, this technique paved the way for us and other researchers in the field of lung cancer to explore intratumoral chemo and other immunotherapies in animal models and in humans.After watching this video, you should have a good understanding of how to treat mediastinal and hilar recurrence of lung cancer with EBUS-guided intratumoral cisplatin injection.

Research

JoVE Journal

Cancer Research

The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues

Metastasis is the major cause of cancer death. The role of circulating tumor cells (CTCs) in promoting cancer metastasis, in which lung colonization by ...

Utilization of Ultrasound Guided Tissue-directed Cellular Implantation for the Establishment of Biologically Relevant Metastatic Tumor Xenografts

Preclinical testing of anticancer therapies relies on relevant xenograft models that mimic the innate tendencies of cancer. Advantages of standard ...

Elastic Staining on Paraffin-embedded Slides of pT3N0M0 Gastric Cancer Tissue

The elastic lamina, which is usually located in the sub-mesothelial layer, adjacent to the peritoneum mesothelial cells, is amphiphilic on hematoxylin and ...

Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma

The recent success of immune checkpoint blockade in melanoma and lung adenocarcinoma has galvanized the field of immuno-oncology as well as revealed the ...

Perfusion and Inflation of the Mouse Lung for Tumor Histology

The ability to evaluate lung histology is critical for the fields of lung cancer research and cancer metastasis. It is equally important to perform ...

Pathological Analysis of Lung Metastasis Following Lateral Tail-Vein Injection of Tumor Cells

Metastasis, the primary cause of morbidity and mortality for most cancer patients, can be challenging to model preclinically in mice. Few spontaneous ...

Modeling Brain Metastases Through Intracranial Injection and Magnetic Resonance Imaging

Metastatic spread of cancer is an unfortunate consequence of disease progression, aggressive cancer subtypes, and/or late diagnosis. Brain metastases are ...

Modeling Brain Metastasis Via Tail-Vein Injection of Inflammatory Breast Cancer Cells

Metastatic spread to the brain is a common and devastating manifestation of many types of cancer. In the United States alone, about 200,000 patients are ...

Generation of an Orthotopic Xenograft of Pancreatic Cancer Cells by Ultrasound-Guided Injection

Pancreatic cancer (PCa) represents one of the deadliest cancer types worldwide. The reasons for PCa malignancy mainly rely on its intrinsic malignant ...

Modeling Brain Metastasis by Internal Carotid Artery Injection of Cancer Cells

Brain metastasis is a cause of severe morbidity and mortality in cancer patients. Critical aspects of metastatic diseases, such as the complex neural ...