Phase II Multicenter Clinical Trial of Pulmonary Metastasectomy and Isolated Lung Perfusion with Melphalan in Patients with Resectable Lung Metastases

WA den Hengst, JMH Hendriks, B Balduyck, I Rodrigus, JB Vermorken, F Lardon, MIM Versteegh, J Braun, H Gelderblom, FMNH Schramel, WJ van Boven, BP van Putte, Ozcan Birim, A.P.W.M. Maat, PEY Van Schil

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Introduction: The 5-year overall survival rate of patients undergoing complete surgical resection of pulmonary metastases (PM) from colorectal cancer (CRC) and sarcoma remains low (20-50%). Local recurrence rate is high (48-66%). Isolated lung perfusion (ILuP) allows the delivery of high-dose locoregional chemotherapy with minimal systemic leakage to improve local control. Methods: From 2006 to 2011, 50 patients, 28 male, median age 57 years (15-76), with PM from CRC (n = 30) or sarcoma (n = 20) were included in a phase II clinical trial conducted in four cardiothoracic surgical centers. In total, 62 ILuP procedures were performed, 12 bilaterally, with 45 mg of melphalan at 37 degrees C, followed by resection of all palpable PM. Survival was calculated according to the Kaplan-Meier method. Results: Operative mortality was 0%, and 90-day morbidity was mainly respiratory (grade 3: 42%, grade 4: 2%). After a median follow-up of 24 months (3-63 mo), 18 patients died, two without recurrence. Thirty patients had recurrent disease. Median time to local pulmonary progression was not reached. The 3-year overall survival and disease-free survival were 57% +/- 9% and 36% +/- 8%, respectively. Lung function data showed a decrease in forced expiratory volume in 1 second and diffusing capacity of the alveolocapillary membrane of 21.6% and 25.8% after 1 month, and 10.4% and 11.3% after 12 months, compared with preoperative values. Conclusion: Compared with historical series of PM resection without ILuP, favorable results are obtained in terms of local control without long-term adverse effects. These data support the further investigation of ILuP as additional treatment in patients with resectable PM from CRC or sarcoma.
Original languageUndefined/Unknown
Pages (from-to)1547-1553
Number of pages7
JournalJournal of Thoracic Oncology
Issue number10
Publication statusPublished - 2014

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