{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:43:07Z","timestamp":1760060587195,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Roswell Park Comprehensive Cancer Center","award":["NCI P30CA016056"],"award-info":[{"award-number":["NCI P30CA016056"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Objectives: We sought to document interim methodologic improvements and preliminary results for pulmonary suffusion. Methods: A Phase I\/II trial of thoracoscopic lung suffusion for resectable sarcoma and colorectal carcinoma metastases followed a pilot study on oligometastatic lung malignancy at a comprehensive cancer center. Primary-specific chemotherapy doses (cisplatin, oxaliplatin, doxorubicin, or gemcitabine) suffused unilaterally for 30 min were escalated to amplify regional deliveries three-fold. Drug delivery was measured with tissue, blood samples, and 99Tc; pulmonary function tests and clinical adverse events (AEs) assessed safety and tolerance. Results: From 2008\u20132025, 31 ECOG 0\u20132 patients (10 male) aged 33\u201375 years had unilateral lung suffusion (16 right, 14 left, 1 aborted, and 8 sides selected randomly). Vascular occlusion intolerance was immediate or delayed (25 min) in two cases. Two catheter-positioning grade 3 AEs occurred: hypotension with troponin leak (1) and atrial fibrillation (1). Patients averaged 1.3 \u00b1 1.2 metastasectomies (17 sub-lobar, 8 lobar resections, and 2 intentional open cytoreductive metastasectomies). Hospitalizations were brief (1\u20134 days) except for 6\u20137 day stays in the only two open cases and one doxorubicin (grade 4 hypoxic respiratory failure) case. Ninety-day survival was 100%, and the Phase I delivery goal of 12.75 mg\/m2 65 (15% systemic) was achieved for oxaliplatin. Lung function was preserved according to 99Tc differentials within 6.1 \u00b1 7.1% of the predicted reductions at 30 days. Sampling delays, tracer discordances, and atypical pharmacokinetics reduced tissue drug detections. Recent pulmonary artery snaring cases (two) demonstrated in-flow control more stable than that of balloon occlusions. Conclusions: Suffusion for metastatic malignancies appears safe and warrants further investigation.<\/jats:p>","DOI":"10.3390\/cancers17172880","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T08:23:38Z","timestamp":1756801418000},"page":"2880","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pulmonary Suffusion Refinements for Primary and Secondary Malignancies: Preliminary Analyses of Phase I Safety and Drug Delivery Data"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4800-2297","authenticated-orcid":false,"given":"Todd","family":"Demmy","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Elm & Carlton Strs., Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samah","family":"Abdelhady","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Roswell Park Comprehensive Cancer Center, Elm & Carlton Strs., Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Garin","family":"Tomaszewski","sequence":"additional","affiliation":[{"name":"Department of Radiology, Roswell Park Comprehensive Cancer Center, Elm & Carlton Strs., Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Petroziello","sequence":"additional","affiliation":[{"name":"Department of Radiology, Roswell Park Comprehensive Cancer Center, Elm & Carlton Strs., Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Radiology, Roswell Park Comprehensive Cancer Center, Elm & Carlton Strs., Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Hennon","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Elm & Carlton Strs., Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Dexter","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Elm & Carlton Strs., Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepak","family":"Vadehra","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Roswell Park Comprehensive Cancer Center, Elm & Carlton Strs., Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6074-9847","authenticated-orcid":false,"given":"Ajay","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Roswell Park Comprehensive Cancer Center, Elm & Carlton Strs., Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Grand\u2018Maison","sequence":"additional","affiliation":[{"name":"Center for Cancer and Oncology Care, Erie County Medical Center, Buffalo, NY 14215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace","family":"Dy","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Roswell Park Comprehensive Cancer Center, Elm & Carlton Strs., Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sai","family":"Yendamuri","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Elm & Carlton Strs., Buffalo, NY 14263, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"ref_1","first-page":"45","article-title":"Epidemiology of Lung Cancer","volume":"25","author":"Thandra","year":"2021","journal-title":"Contemp. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Stella, G.M., Kolling, S., Benvenuti, S., and Bortolotto, C. (2019). Lung-Seeking Metastases. Cancers, 11.","DOI":"10.3390\/cancers11071010"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1186\/s13019-021-01740-3","article-title":"Survival Prognostic and Recurrence Risk Factors after Single Pulmonary Metastasectomy","volume":"16","author":"Forster","year":"2021","journal-title":"J. Cardiothorac. Surg."},{"key":"ref_4","first-page":"ivae028","article-title":"Outcomes and Prognostic Factors of Repeat Pulmonary Metastasectomy","volume":"38","author":"Kanzaki","year":"2024","journal-title":"Interdiscip. Cardiovasc. Thorac. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1590\/S1807-59322009000600008","article-title":"Surgical Resection of Lung Metastases: Results from 529 Patients","volume":"64","author":"Younes","year":"2009","journal-title":"Clinics"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kessel, K.A., Grosser, R.C.E., Kraus, K.M., Hoffmann, H., Oechsner, M., and Combs, S.E. (2020). Stereotactic Body Radiotherapy (Sbrt) in Patients with Lung Metastases\u2014Prognostic Factors and Long-Term Survival Using Patient Self-Reported Outcome (Pro). BMC Cancer, 20.","DOI":"10.1186\/s12885-020-6635-8"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s12943-025-02318-6","article-title":"Lung-Specific Metastasis: The Coevolution of Tumor Cells and Lung Microenvironment","volume":"24","author":"Xiao","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13019-022-01757-2","article-title":"The Full Cohort of 512 Patients and the Nested Controlled Trial in 93 Patients in the Pulmonary Metastasectomy in Colorectal Cancer (Pulmicc) Study Raise Doubts About the Effective Size at Present Claimed","volume":"17","author":"Treasure","year":"2022","journal-title":"J. Cardiothorac. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1177\/0267659106073984","article-title":"Isolated Lung Perfusion for Pulmonary Metastases, a Review and Work in Progress","volume":"21","author":"Grootenboers","year":"2006","journal-title":"Perfusion"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.thorsurg.2005.11.003","article-title":"Isolated Lung Perfusion for Pulmonary Metastases","volume":"16","author":"Hendriks","year":"2006","journal-title":"Thorac. Surg. Clin."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.thorsurg.2015.12.002","article-title":"Novel Technologies for Isolated Lung Perfusion: Beyond Lung Transplant","volume":"26","author":"Cypel","year":"2016","journal-title":"Thorac. Surg. Clin."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.thorsurg.2015.09.008","article-title":"Isolated Lung Perfusion for Pulmonary Metastases","volume":"26","author":"Ward","year":"2016","journal-title":"Thorac. Surg. Clin."},{"key":"ref_13","unstructured":"Ramadan, K., Garza, G., Montagne, J., Gokhale, H., Shan, H., Keshavjee, S., Yasufuku, K., Wakeam, E., Waddell, T., and Cypel, M. (2025, January 2\u20135). Phase I Dose Escalation Clinical Trial Using a Novel in Vivo Lung Perfusion Strategy in Patients with Multiple Pulmonary Metastases from Colorectal Carcinoma. Proceedings of the 105th Annual Meeting, Seattle, WA, USA."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1089\/jamp.2025.19211.js","article-title":"Inhaled Chemotherapy","volume":"38","author":"Subramanian","year":"2025","journal-title":"J. Aerosol Med. Pulm. Drug Deliv."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.lungcan.2012.04.006","article-title":"Prospective Study of Transarterial Infusion of Docetaxel and Cisplatin to Treat Non-Small-Cell Lung Cancer in Patients Contraindicated for Standard Chemotherapy","volume":"77","author":"Nakanishi","year":"2012","journal-title":"Lung Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1055\/s-0033-1342959","article-title":"Regional Chemotherapy of the Lung: Transpulmonary Chemoembolization in Malignant Lung Tumors","volume":"30","author":"Vogl","year":"2013","journal-title":"Semin. Interv. Radiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhang, F., and Liu, Y. (2025). Transcatheter Arterial Chemoembolization for Lung Malignant Tumors. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1551644"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"571","DOI":"10.2147\/DDDT.S46393","article-title":"Intratumoral Chemotherapy for Lung Cancer: Re-Challenge Current Targeted Therapies","volume":"7","author":"Zarogoulidis","year":"2013","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/imi.0b013e31820b1e63","article-title":"Regional Lung Chemotherapy Techniques","volume":"6","author":"Mallick","year":"2011","journal-title":"Innovations"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.athoracsur.2009.04.101","article-title":"Thoracoscopic Organ Suffusion for Regional Lung Chemotherapy (Preliminary Results)","volume":"88","author":"Demmy","year":"2009","journal-title":"Ann. Thorac. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1002\/jso.2930180305","article-title":"Regional Chemotherapy Via the Pulmonary Artery for Pulmonary Metastases","volume":"18","author":"Karakousis","year":"1981","journal-title":"J. Surg. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/S0022-5223(19)32588-7","article-title":"Selective Chemotherapy of the Lung during Unilateral Pulmonary Arterial Occlusion with a Balloon-Tipped Catheter","volume":"40","author":"Smyth","year":"1960","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1007\/BF02256589","article-title":"Isolated Lung Chemotherapeutic Infusions for Treatment of Pulmonary Metastases: A Pilot Study","volume":"9","author":"Demmy","year":"2002","journal-title":"J. Biomed. Sci."},{"key":"ref_24","unstructured":"Brobeck, J.R. (1979). The Cardiovascular System and Blood Flow. Best & Taylor\u2019s Physiologic Basis of Medical Practice, Williams & Wilkins."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.xjon.2024.12.012","article-title":"Preclinical Experience with Cisplatin, Gemcitabine, and Doxorubicin in Pulmonary Suffusion","volume":"24","author":"Nitsche","year":"2025","journal-title":"JTCVS Open"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.thorsurg.2015.09.013","article-title":"Thoracoscopic Lung Suffusion","volume":"26","author":"Demmy","year":"2016","journal-title":"Thorac. Surg. Clin."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1310\/hpj4807-550","article-title":"Docetaxel and Cisplatin Regimen for Non-Small-Cell Lung Cancer","volume":"48","author":"Yang","year":"2013","journal-title":"Hosp. Pharm."},{"key":"ref_28","unstructured":"National Comprehensive Cancer Network (2025). Colon Cancer, National Comprehensive Cancer Network. Available online: https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/colon.pdf."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/S1470-2045(17)30622-8","article-title":"Gemcitabine and Docetaxel Versus Doxorubicin as First-Line Treatment in Previously Untreated Advanced Unresectable or Metastatic Soft-Tissue Sarcomas (Geddis): A Randomised Controlled Phase 3 Trial","volume":"18","author":"Seddon","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.critrevonc.2015.10.020","article-title":"Gemcitabine-Based Chemotherapy in Sarcomas: A Systematic Review of Published Trials","volume":"98","author":"Ducoulombier","year":"2016","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1183\/13993003.02089-2015","article-title":"Use of the Modified Borg Scale and Numerical Rating Scale to Measure Chronic Breathlessness: A Pooled Data Analysis","volume":"47","author":"Miriam","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.5858\/arpa.2021-0287-OA","article-title":"Updating Normal Organ Weights Using a Large Current Sample Database","volume":"146","author":"Bell","year":"2022","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1093\/icvts\/ivt526","article-title":"Adrenalectomy for Isolated Metastasis from Operable Non-Small-Cell Lung Cancer","volume":"18","author":"Sastry","year":"2014","journal-title":"Interact. Cardiovasc. Thorac. Surg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100253","DOI":"10.1016\/j.jhlto.2025.100253","article-title":"Fluid Management of Cardiopulmonary Bypass during Pulmonary Endarterectomy for Cteph Patients Impacts Perioperative Outcome","volume":"9","author":"Furrer","year":"2025","journal-title":"JHLT Open"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.lungcan.2007.12.017","article-title":"Multi-Arterial Infusion Chemotherapy for Non-Small Cell Lung Carcinoma--Significance of Detecting Feeding Arteries and Tumor Staining","volume":"61","author":"Nakanishi","year":"2008","journal-title":"Lung Cancer"},{"key":"ref_36","first-page":"1","article-title":"Selective Pulmonary Artery Perfusion with Blood Flow Occlusion Delivers Concentrated Levels of Chemotherapy to Ipsilateral Hilar and Mediastinal Lymph Nodes","volume":"5","author":"Sparks","year":"2014","journal-title":"World J. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100918","DOI":"10.1016\/j.jpha.2023.12.008","article-title":"Perspective on In vivo SPME for Human Applications: Starting from Monitoring Doxorubicin during Lung Chemo-Perfusion","volume":"14","author":"Zhou","year":"2024","journal-title":"J. Pharm. Anal."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Jiang, R.W., Zhou, W., Cypel, M., Demmy, T.L., Shafirstein, G., Garza, G., Gawrys, E., Bogusiewicz, J., Bojko, B., and Pawliszyn, J. (2025). Minimally Invasive Chemical Biopsy Needle with Self-Wettable Extraction Phase for in Vivo Tissue Sampling during Medical Procedures. Adv. Sci. (Weinh), e00396. (in press).","DOI":"10.1002\/advs.202500396"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Yue, X., Cui, J., Huang, S., Liu, W., Qi, J., He, K., and Li, T. (2025). An Interpretable Radiomics-Based Machine Learning Model for Predicting Reverse Left Ventricular Remodeling in Stemi Patients Using Late Gadolinium Enhancement of Myocardial Scar. Eur. Radiol., (in press).","DOI":"10.1007\/s00330-025-11419-1"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhan, Y., Song, F., Zhang, W., Gong, T., Zhao, S., and Lv, F. (2024). Prediction of Benign and Malignant Pulmonary Nodules Using Preoperative CT Features: Using PNI-GARS as a Predictor. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1446511"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/17\/2880\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:37:37Z","timestamp":1760035057000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/17\/2880"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,2]]},"references-count":40,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["cancers17172880"],"URL":"https:\/\/doi.org\/10.3390\/cancers17172880","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2025,9,2]]}}}