S1956 clinical utility of this liquid biopsy for response monitoring is under investigation. The aim of this study was to evaluate liquid biopsy as tool for monitoring response to treatment in a prospective cohort of ALK-positive NSCLC patients. Method: Consecutive ALK positive NSCLC patients treated with systemic therapies in our institution were enrolled. After informed consent, blood samples were prospectively collected for longitudinal analysis during treatment and at progression. Exosomal RNA and cfDNA co-isolated from plasma was used for detection of EML4-ALK fusion RNAs by the qPCR-based ExoDx Lung(ALK)TM-test as well as for analysis of ALK-resistance mutations by ExoDx NGS sequencing. Result: From Aug 2016 to date, 23 patients were enrolled in the study, 14 (61%) were females, 15 (65%) non-smokers, median age of 50 years (23-76). All patients had adenocarcinoma and were tissue positive for ALK by immunohistochemistry 14 (61%) and/or FISH 16 (70%). Nineteen patients (83%) had stage IV disease at diagnosis, with brain involvement in 7 patients (37%), bone in 11 (48%) and liver in 2 (11%). The median number of ALK inhibitors received was 2 (0-4). Twenty-one patients (91%) received ALK inhibitors (5 crizotinib, 3 ceritinib, 13 next-generation inhibitors) and 2 chemotherapy, with an objective response rate of 48%. Five out of 8 patients (63%) that were treatment naïve (baseline) or progressive disease (PD) at the time of collection, were positive for EML4-ALK by liquid biopsy, 1 of 4 samples (25%) at baseline, and 4 of 4 samples (100%) at PD, were positive by liquid biopsy. EML4-ALK variant 1 was detected in two (40%) and variant 3 in three patients (60%). All 26 samples collected during objective response or stable disease (100%) were negative for EML4-ALK by liquid biopsy. The ALK resistance mutation panel was performed on 2 samples from patients with PD, and both were detected positive for ALK resistance mutations, L1196M (variant 1) and G1202R (variant 3), respectively. Conclusion: The monitoring of ALK fusions on exosomal RNA by liquid biopsy is applicable in the clinic and closely correlated to disease control. ALK mutations detection using liquid biopsy can be an accurate tool for assessing the resistance to ALK inhibitors. Updated results from up to 30 patients will be available for the final presentation.
P1.03-014 Saline Alone vs Saline plus Mannitol Hydration for the Prevention of Acute Cisplatin Nephrotoxicity: A Randomized Trial W. Dela Cruz, F. Flynt, S. Terrazzino, N. Hullinger, M. King, J. Aden, D. Nelson, T. Byrd Department of Medicine, Hematology-Oncology Service, San Antonio Military Medical Center, San Antonio, TX/US Background: Cisplatin is widely used as an effective chemotherapy in diverse neoplasms and is associated with renal toxicity. Several studies suggest that pre-hydration plus mannitol prior to chemotherapy with cisplatin prevents nephrotoxicity. The aim of this study is to determine the acute effects of hydration plus mannitol on renal function in patients receiving cisplatin. Method: Fifty patients who were eligible to receive chemotherapy with cisplatin alone or in combination with other chemotherapy were randomized to receive 1L saline alone (A) or saline plus mannitol before and after chemotherapy. The mannitol group received 12.5 g of mannitol in saline solution. Serum Creatinine (Ser Cr), BUN, and GFR were measured at baseline (no more than 3 days prior to therapy) and on Day 1, 5, and 14. Baseline characteristics were analyzed using t-tests or chi-squared tests. Repeated Measures (RM) ANOVA was used to compare the change in BUN, creatinine, GFR, and BUN to Creatinine ratio. Result: Data for 48 patients (36 male and 12 female) were collected. The median age is 57 (range 18 to 78); 23 received saline alone and 25 received mannitol. There are no difference between
Journal of Thoracic Oncology
Vol. 12 No. 11S2
randomized groups between Age, Gender, and Race. The mean BUN and BUN to creatinine ratio significantly increased by 46% and 37% respectively (p <0.001), while the corresponding mean Serum Cr did not significantly change over time and mean GFR peaked at day 1 then decreased by day 5 (p¼0.001). All variables returned to baseline by Day 15. Twenty patients (42%) had grade 1 increase in Ser Cr (25% in A and 17% in B, p¼0.078). No patients had grade 2 or greater in the mannitol group, while 2 patients had grade 2 or grade 3 in saline-only group. RM ANOVA analysis shows no difference between randomized groups from baseline through Day 1, Day 5, and Day 14 for BUN, creatinine, GFR, and BUN to Creatinine ratio. Conclusion: Cisplatin caused acute decline in renal function as determined by BUN, BUN to Ser Cr ratio and GFR, however, addition of mannitol to pre-hydration fluid did not change the outcome. Keywords: Cisplatin, Cisplatin, acute renal toxicity, mannitol, Mannitol
P1.03-015 The Relationship between the UGT1A1*27 and UGT1A1*7 Genetic Polymorphisms and IrinotecanRelated Toxicities in Patients with Lung Cancer M. Fukuda,1 M. Okumura,2 K. Arimori,2 A. Takahira,3 M. Mori,3 D. Nakamura,3 M. Shimada,4 H. Taniguchi,4 H. Gyotoku,4 H. Senju,4 T. Ikeda,4 H. Yamaguchi,4 K. Nakatomi,4 T. Tsuchiya,1 H. Mukae,4 K. Ashizawa3 1Clinical Oncology Center, Nagasaki University Hospital, Nagasaki/JP, 2Department of Pharmacy, Faculty of Medicine, University of Miyazaki Hospital, Miyazaki/JP, 3Department of Clinical Oncology, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki/JP, 4Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki/JP Background: Genetic polymorphisms in the UDP-glucuronosyltransferase 1A1 (UGT1A1), UGT1A7, and UGT1A9 genes are associated with interindividual differences in irinotecan toxicities. Purpose: To evaluate the effects of gene polymorphisms, including UGT1A1*7, *27, and *29, on the safety of irinotecan therapy. Method: The eligibility criteria were as follows: lung cancer patients who were scheduled to undergo irinotecan therapy, aged 20 years, and had a performance status of 0-2. After informed consent had been obtained, patients were enrolled, and their blood was collected and used to examine the frequency of the UGT1A1*6, *7, *27, *28, and *29 polymorphisms and the drug concentrations of irinotecan, SN-38, and SN-38G after irinotecan therapy. Result: Thirty-one patients were enrolled. The patients’ characteristics were as follows: male/female ¼ 25/6, median age (range) ¼ 71 (55-84), stage IIB/ IIIA/IIIB/IV ¼ 2/6/11/12, and Ad/Sq/Sm/Oth ¼ 14/10/3/4. The -/-, *6/-, *7/-, *27/-, *28/-, and *29/- UGT1A1 gene polymorphisms were observed in 10 (32%), 10 (32%), 2 (6%), 2 (6%), 7 (23%), and 0 (0%) cases, respectively. There were no homozygous or complex heterozygous polymorphisms. The UGT1A1*27 polymorphism occurred separately from the UGT1A1*28 polymorphism. The lowest leukocyte counts of the patients with the UGT1A1*27 and UGT1A1*6 gene polymorphisms were lower than those seen in the wild-type patients. SN-38 tended to remain in the blood for a prolonged period after the infusion of irinotecan in patients with the UGT1A1*27 or UGT1A1*28 polymorphism. No severe myelotoxicity was seen in the patients with UGT1A1*7. Conclusion: UGT1A1*27 and UGT1A1*7 are both rare gene polymorphisms. UGT1A1*27 can occur separately from UGT1A1*28 in some circumstances and is related to leukopenia during irinotecan treatment. UGT1A1*7 is less relevant to irinotecan-induced toxicities, and UGT1A1*29 seems to have little clinical impact. Keywords: polymorphism, UGT1A1*27, UGT1A1*7