bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of preoperative modified FOLFIRINOX (mFOLFIRINOX) followed by postoperative gemcitabine (GEM) in patients (pts) with borderline resectable pancreatic ductal adenocarcinomas (BR-PDAC).
Authors: Yoo Changhoon , Kim Kyu-Pyo , Song Ki Byung , Lee Sang Soo , Park Do Hyun , Song Tae Jun , Lee Seung Soo , Park Jin-hong , Hwang Dae Wook , Lee Jae Hoon , Shin Sang Hyun , Shin Eunseon , Ryoo Baek-Yeol , Kim Song Cheol 
Published: January 2019

342 Background: mFOLFIRINOX and GEM are standard chemotherapy for metastatic and resected PDAC, respectively. This phase 2 trial assessed the efficacy and safety of perioperative chemotherapy consisted of preoperative mFOLFIRINOX and postoperative GEM in pts with BR-PDAC. Methods: Pts with histologically proven and radiologically confirmed BR-PDAC as defined by NCCN criteria were eligible. Pts received 8 cycles of preoperative mFOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, 5-FU 2,400 mg/m2 over 46 hours, and leucovorin 400 mg/m2), every 2 weeks. For pts who underwent surgery, postoperative GEM (1,000 mg/m2 D1, 8, 15, every 4 weeks) was given for 6 cycles. Primary endpoint was 1-year progression-free survival (PFS) rate and secondary endpoints were PFS, overall survival (OS) and curative surgery rate. A total of 44 pts were required to show the improvement in 1-year PFS rates from 30% to 50% with a two-sided alpha of 0.05, beta of 0.8 and drop-out rates of 10%. Results: Between May/2016 and Mar/2018, 44 patients were enrolled. Median age was 60 years (range, 35-76) and 26 pts (59%) were male. Pancreas head was most common site (n = 26, 59%). With mFOLFIRINOX, response rate was 34% and surgery was done in 27 patients (61%); 22 and 5 patients achieved R0 and R1 resection, respectively, and postoperative GEM was given in 24 patients (89%). With median follow-up of 16.6 months (95% CI, 10.9-22.2), 1-year PFS rate was 51.7% (95% CI, 35.2-68.2), and median PFS and OS was 13.0 months (95% CI, 7.7-18.4), and 14.3 months (95% CI, not available), respectively. PFS and OS were significantly differed according to the surgery (p < 0.001 for both) and response to mFOLFIRINOX (p < 0.001 and p = 0.03, respectively). Relative dose intensities of irinotecan, oxaliplatin and 5-FU were > 77% during mFOLFIRINOX. Grade 3-4 neutropenia (55%), anemia (14%), nausea (11%), and diarrhea (7%) were most common severe toxicities and 3 pts (7%) discontinued mFOLFIRINOX due to the toxicities. Conclusions: Perioperative chemotherapy using mFOLFIRINOX and GEM were feasible and effective for pts with BR-PDAC. Future randomized trial is warranted. Clinical trial information: NCT02749136.
Effect of neoadjuvant chemoradiotherapy on prognosis in resectable and borderline resectable pancreatic cancer with venous involvement.
Authors: Nagai Minako , Sho Masayuki , Akahori Takahiro , Nakagawa Kenji , Nakamura Kota , Takagi Tadataka , Tanaka Toshihiro , Nishiofuku Hideyuki , Kichikawa Kimihiko , Ikeda Naoya 
Published: January 2019

343 Background: The efficacy of neoadjuvant treatment for pancreatic cancer (PC) remains to be established. In this study, we have retrospectively evaluated the impact of neoadjuvant chemoradiothrapy (NACRT) on perioperative and long-term clinical outcome in PC. Methods: One hundred eighty one patients who preoperatively received full-dose gemcitabine (1000mg/m2) with concurrent radiation of 54 Gy between 2006 and 2017 were analyzed. One hundred forty nine patients who proposed upfront surgery were served as control. Results: Among the 181 patients treated with NACRT, 23 (13%) couldn’t undergo pancreatic resection after NACRT because of distant metastasis in 10, tumor progression in 7 and poor PS in 6. While among the 149 patients who proposed upfront surgery, 10 (7%) couldn’t undergo pancreatic resection at laparotomy, because of distant metastasis in 8 and tumor progression in 2. In overall survival analysis of all patients with resected and unresected tumor, patients treated with NACRT had a better prognosis than those without (median survival time: 37.0 vs. 27.1M, P = 0.049). According to tumor resectability status including R (resectable), BR-P (borderline resectable with venous involvement) and BR-A (borderline resectable with arterial involvement) PC, in the R and BR-P group, overall survival was significantly better in the patients with NACRT (45.7 vs. 33.8M, P = 0.049, 61.7 vs. 14.6M, P = 0.002). Also only for resected tumors, patients treated with NACRT had a better prognosis than those without in the R and BR-P group (53 vs. 36.5M, P = 0.033, 61.7 vs. 14.6M, P = 0.002), while NACRT had no significant impact on prognosis in the BR-A group. The rate of pancreatic fistula, delayed gastric emptying and abdominal abscess were lower in the NACRT group than the control group. Furthermore, the lymph node metastasis rate, R0 resection rate and pathological stage were favorable in the NACRT group (P < 0.001, P = 0.005, P < 0.001). The completion rate of adjuvant chemotherapy was also higher in the NACRT group (P = 0.001). Conclusions: NACRT had a variety of favorable impact in PC treatment. In particular, it significantly improved the prognosis in the R and BR-P, but not BR-A.
Changes in alpha-fetoprotein (AFP) and systemic therapy outcomes in advanced hepatocellular carcinoma (HCC): A multicenter retrospective analysis.
Authors: Bocobo Andrea Grace , Bracci Paige M. , Parks Anna , Hannan Lindsay Marie , Bauer Kelly , Goyal Lipika , Gordan John Dozier , Venook Alan P. , Harris William Proctor , Kelley Robin Kate 
Published: January 2019

346 Background: AFP is elevated in 70% of HCC and is associated with poor prognosis. The role of AFP as a biomarker of response to systemic treatments has not been established, though small, retrospective studies show association between AFP decline and survival on sorafenib. The relationship between AFP changes and response to immune checkpoint inhibitors (CPI) has not been reported. This study examines AFP changes on treatment for association with outcomes on first-line (1L) SOR and any subsequent CPI in a contemporary, multicenter U.S. population. Methods: Design: Multicenter retrospective case series. Key eligibility: Received 1L SOR or SOR-based combination for advanced HCC; ≥ 1 post-treatment AFP value available; enrolled on IRB-approved registry. Objectives: associate AFP changes within 3 months of start of treatment with overall survival (OS) and time on treatment (TOT) on 1L SOR and any subsequent CPI; associate baseline AFP with OS and TOT for SOR and CPI; relate baseline AFP and changes on treatment to clinical covariates. Results: 152 patients were identified from two centers. Baseline characteristics: M/F 132/20; HBV/HCV/nonviral 40/71/41; Child Pugh A/B 128/23; BCLC A/B/C: 4/15/133. Baseline AFP < 20/ ≥ 400: 43/59. 43 received CPI after SOR. See Table. Baseline AFP was not related to TOT or OS for SOR or CPI. Multivariable analyses for AFP with clinical covariates will be presented. Conclusions: This series is the largest multicenter analysis of AFP response to systemic therapy with SOR and CPI. AFP decrease and increase within the first 3 months of treatment with SOR and CPI were inversely and significantly associated with median OS. AFP warrants further study in randomized cohorts as a biomarker of response to systemic therapy in HCC, now with multiple treatment options available at progression.[Table: see text]
Real world usage of gemcitabine and nabpaclitaxel in older adults with metastatic pancreatic cancer: A single institution experience.
Authors: Winer Arthur , Handorf Elizabeth A. , Nagappan Lavanya , Blumenreich Aryeh , Chowdhury Farhana , Vijayvergia Namrata , Dotan Efrat 
Published: January 2019

358 Background: The median age at diagnosis for metastatic pancreatic cancer (mPC) is 72. Gemcitabine and Nab-Paclitaxel (GA) is often the preferred chemo regimen in this population due to presumed reduced toxicity compared with FOLFIRINOX. While the traditional GA schedule (TDS) includes treatment on days 1, 8, and 15 of a 28-day cycle, it can cause side effects and patients often require dose reductions. There is data for a modified dosing schedule (MDS) treating only on day 1 and 15. Therefore, we retrospectively analyzed our older adults treated with GA using the TDS versus the MDS and compared tolerability and outcomes between the two groups. Methods: We identified pts with mPC >64 y/o treated with GA at Fox Chase Cancer Center between 1/2010 - 7/2018 and collected their demographic, disease and treatment information. We analyzed discrete variables using Fisher’s exact test and continuous variables using Wilcoxon tests. Overall survival (OS) was analyzed by the Kaplan-Meier method and Cox proportional hazards regression. Results: Fifty-six pts were identified with a median age at diagnosis of 71 (range: 64-90) and 67.8% with metastatic disease at presentation. 57% received GA in the first line. 44% were treated with TDS while 56% received a MDS; an older median age was seen in the MDS group (73 vs 69 y/o, p<0.001). Up front dose reductions of GA were seen in 24% in the TDS vs 48% in MDS, and they were more common with nab-paclitaxel (26% in MDS vs 10% in TDS) than with gemcitabine (two pts in TDS vs one pt in MDS). Of pts who began with TDS only 11 (19% of all pts) were able to tolerate it without adjustment throughout treatment; 14 (25%) transitioned to the MDS. More pts suffered grade ≥3 toxicity with the TDS vs. MDS (68% vs. 51%; p=0.27) and more required a dose reduction (TDS 72% vs. MDS 48%; p=0.1). 58% required an additional GA dose reduction over the course of treatment. Median OS among GA treated pts in the front line (n=32) was not significantly different (MDS: 11.7 mo vs. TDS: 13 mo; p=0.1). Conclusions: These results demonstrate tolerability and similar efficacy of the GA MDS among older adults with mPC. Given the limited sample size, further studies are required to help establish the appropriate therapy for older patients.
Update result of HGCSG 1403: Phase I trial of oxaliplatin/irinotecan/S-1 (OX-IRIS) as first-line chemotherapy for unresectable pancreatic cancer.
Authors: Nakano Shintaro , Kawamoto Yasuyuki , Yuki Satoshi , Yagisawa Masataka , Sawada Kentaro , Muranaka Tetsuhito , Nakatsumi Hiroshi , Saiki Takuro , Ishiguro Atsushi , Harada Kazuaki , Kobayashi Yoshimitsu , Iwanaga Ichiro , Hatanaka Kazuteru , Sakata Yuh , Komatsu Yoshito 
Published: January 2019

359 Background: FOLFIRINOX has become one of the standard treatment for unresectable pancreatic cancer with distant metastasis. OX-IRIS is the combination therapy of oxaliplatin (L-OHP), irinotecan (IRI) and S-1. It is the useful treatment to dispense with a continuous infusion of 5FU by administering S-1 orally. For establishing OX-IRIS therapy as a new standard treatment, we planned this study for evaluating dose limiting toxicity (DLT) and maximum tolerated dose (MTD). Methods: This study was carried out as a multicenter phase I study. Chemotherapy-naïve patients with unresectable pancreatic cancer were included. L-OHP and IRI were administered on day 1 and 15, and S-1 was taken twice a day in day 1-14, and then 14 days were rest for 1 cycle. The primary endpoints were the frequency of DLT and estimating of MTD. Secondary endpoints were safety, response rate, progression-free survival (PFS) and overall survival (OS). Results: Between January 2016 and August 2017, 13 cases were enrolled. The patients’ backgrounds were median age 62; male /female, 9/4; the primary tumor sites head /body and tail, 8/5; ECOG PS 0/1, 7/6; UR-LA /UR-M, 4/9. Two of five enrolled in level 0 (L-OHP: 85 mg/m2, IRI: 100 mg/m2, S-1: 80 mg/m2) had DLT. One of six in level -1 (L-OHP: 65 mg/m2, IRI: 100 mg/m2, S-1: 80 mg/m2) had DLT. At level 0, 100% of cases had anemia and fatigue, 80% anorexia, diarrhea, peripheral sensory neuropathy, 60% platelet count decrease. At level -1, 100% had anemia, 75% nausea and fatigue, 63% anorexia. Response rate was 10% and disease control rate was 70% in ten cases with evaluable lesion. Median PFS was 4.1 months (95%C.I.; 0.0-8.6 months). Median OS was 13.7 months (95%C.I.; 5.9-21.5 months). Conclusions: In this study, MTD was estimated to be level 0, and determined recommended dose is level -1 for the planned future study. We are going to evaluate efficacy and safety in a phase II study. (UMIN ID: 000017002) Clinical trial information: 000017002.
FOLFIRINOX in pancreatic cancer patients age 75 years or older.
Authors: Mizrahi Jonathan , Rogers Jane , Hess Kenneth R. , Wolff Robert A. , Varadhachary Gauri Rajani , Shroff Rachna T. , Ho Linus , Fogelman David R. , Raghav Kanwal Pratap Singh , Overman Michael J. , Pant Shubham 
Published: January 2019

362 Background: Although FOLFIRINOX (5-Fluorouracil + leucovorin + irinotecan + oxaliplatin) is now the standard of care for patients (pts) with metastatic pancreatic cancer (PC) based on the 2011 study by Conroy et al. which demonstrated improved median overall survival (mOS) (11.1 vs 6.8 months [m] with gemcitabine, P < 0.001), pts > 75 yrs old were excluded from this study. As per SEER 2011-2015 data, 38% of new PC cases are diagnosed in pts age > 75. The purpose of this study was to assess the safety and efficacy of FOLFIRINOX in this group of pts. Methods: We retrospectively analyzed unresectable PC pts, age ≥ 75, treated with FOLFIRINOX at MD Anderson since 2011. Data obtained include demographics, line of treatment (tx), starting dose, progression free survival (PFS), OS and toxicities. Response was determined by chart documentation. Primary outcomes were mOS and rates of grade 3/4 hematologic toxicity (HT). Results: A total of 24 pts (19 male) were included with median age of 76 (range 75 to 84). 18 had metastatic disease, and FOLFIRINOX was the 1st line of tx for 18 of the 24 pts. The median number of cycles administered was 4 (range 1 to 12). The most frequent starting doses of infusional 5-FU, irinotecan and oxaliplatin were 2400, 150 and 75 mg/m2, respectively. Bolus 5-FU and leucovorin were omitted in all but 3 pts. Median PFS was 3.7 m (95% CI: 3.0-5.7) with mOS of 11.6 m (95% CI: 6.14-15.7). 16 pts (67%) experienced disease control (response to tx or stable disease). Grade 3 or 4 HT occurred in 11 pts (46%), and 9 (38%) were supported with granulocyte colony-stimulating factor at some point during tx. 6 pts (25%) required hospital admission for any toxicity, most commonly infection (3 pts), and 10 (42%) stopped FOLFIRINOX due to toxicity, most commonly fatigue (6 pts). Conclusions: In this single-center retrospective analysis of 24 unresectable PC pts age 75 or older given FOLFIRINOX, OS outcomes were similar to those reported by Conroy et al in the original trial which excluded pts older than 75. In our review, toxicities including incidences of grade 3 or 4 HT were similar to those reported in the initial study. These data indicate that the use of modified dosing FOLFIRINOX in advanced PC pts older than 75 appears to maintain similar efficacy and toxicity when compared to younger pts.
Phase II study of pembrolizumab-based therapy in previously treated extrapulmonary poorly differentiated neuroendocrine carcinomas: Results of Part A (pembrolizumab alone).
Authors: Mulvey Claire , Raj Nitya Prabhakar , Chan Jennifer A. , Aggarwal Rahul Raj , Cinar Pelin , Hope Thomas A , Kolli Kanti , Zhang Li , Calabrese Susan , Grabowsky Jennifer Ann , Modarresi Lila , Kelly Virginia , Stonely Danielle , Munster Pamela N. , Reidy Diane Lauren , Fong Lawrence , Bergsland Emily K. 
Published: January 2019

363 Background: Immune checkpoint inhibitor (CPI) efficacy has not been established in extrapulmonary poorly-differentiated neuroendocrine carcinomas (EP-PDNECs). In small cell lung cancer, promising antitumor activity of CPI led to accelerated approval of nivolumab in 8/2018. We investigated the efficacy and safety of pembrolizumab (PEM)-based therapy in biomarker-unselected EP-PDNECs. Methods: Open label, multicenter, phase 2 study of PEM-based therapy in patients (pts) with EP-PDNECs, excluding Merkel cell carcinoma and well differentiated grade 3 NET, with progression on first-line systemic therapy, ECOG 0-1, and adequate hepatic and renal function. Enrollment via an adaptive Simon’s 2-stage design. Plan for 14 pts treated with PEM alone (Part A Stage 1) 200 mg IV every 3 weeks. If > 2 of 14 pts respond by week 18, then 21 additional pts enroll in Part A Stage 2, corresponding to H0 10% vs. H1 26% response rate (RR) at type I error 0.05 with power 80%. Otherwise study proceeds to Part B: PEM plus chemotherapy (dealer's choice of weekly irinotecan or paclitaxel). Primary endpoint is objective RR (ORR) by RECIST 1.1. Secondary endpoints include safety, overall survival, and progression-free survival (PFS). Serial blood samples and baseline tumor biopsies required in all pts for future biomarker studies. Results: Preliminary data from Part A Stage 1 are available. Of 14 pts enrolled, male/female 9/5; median age 63; 1 large cell, 11 small cell, 2 NOS. Primary site of disease: GI 43%, GU 29%, and other 29%. Median Ki67 80% (available for 9 pts). Best response: CR (1), PR (0), SD (2), PD (10), unevaluable (1; early death from sepsis) for ORR 7%. Median PFS was 58 days. Six (43%) pts went off study for early PD or clinical deterioration before first scheduled scan at 9 weeks. PEM was well tolerated with no grade 3-5 AEs attributed to therapy. At last follow up, 9 (64%) pts were alive with 1 pt still on treatment after 19 cycles. Conclusions: PEM monotherapy was not effective in this pretreated, biomarker-unselected population of EP-PDNECs arising in different organs. Part B (PEM plus chemotherapy) enrollment is ongoing. Biomarker studies are planned (Parts A/B). Clinical trial information: NCT03136055.
The influence of renal function on gemcitabine-based chemotherapy for advanced biliary tract cancer: An exploratory subgroup analysis of JCOG1113.
Authors: Ueno Makoto , Morizane Chigusa , Okusaka Takuji , Ogawa Gakuto , Sato Yuya , Ikeda Masafumi , Ozaka Masato , Sugimori Kazuya , Fukutomi Akira , Hara Hiroki , Mizuno Nobumasa , Yanagimoto Hiroaki , Sano Keiji , Tobimatsu Kazutoshi , Yane Kei , Nakamori Shoji , Sata Naohiro , Nishina Tomohiro , Ishii Hiroshi , Furuse Junji 
Published: January 2019

368 Background: JCOG1113 is a randomized phase III trial to evaluate gemcitabine (GEM) plus S-1 (GS) versus GEM plus cisplatin (GC) regarding overall survival (OS) for advanced biliary tract cancer (BTC) (UMIN000001685) and the non-inferiority of GS was demonstrated. It is necessary to consider renal function using cisplatin or S-1 because cisplatin has renal toxicity, and the toxicity of S-1 is affected by renal function. Therefore, we evaluated the influence of renal function on the efficacy and safety of GC and GS in JCOG1113. Methods: All enrolled patients (pts) in JCOG1113 (n = 354) were analyzed. Eligibility criteria included chemotherapy-naïve pts with recurrent or unresectable biliary tract adenocarcinoma, ECOG-PS of 0–1, CCr > 50 ml/min, and adequate organ function. Renal function was classified into two groups by creatinine clearance (CCr) as calculated by the Cockcroft-Gault formula; high CCr (CCr ≥ 80 ml/min) or low CCr (80 > CCr ≥ 50 ml/min). The impact of renal function on OS and progression-free survival (PFS) were compared using the Cox regression model. The adverse events (AEs) were compared using Fisher’s exact test. Results: Eighty-eight pts on GC and 88 pts on GS were included in the high CCr group, and 87 pts on GC and 91 pts on GS were included in the low CCr group. There were no differences between the groups regarding, sex, PS, primary site, biliary drainage, operation, or recurrence, except for age. The hazard ratio (HR) of GS to GC for OS was 1.12 (95% CI 0.81–1.56) in the high CCr group and 0.80 (95% CI 0.58–1.11) in the low CCr group. The HR of GS to GC for PFS was 1.06 (95% CI 0.78–1.44) in the high CCr group and 0.69 (95% CI 0.50–0.94) in the low CCr group. Grade 3-4 AEs of white blood cell count decreased (35.3%/23.6%), anemia (29.4%/7.9%) and platelet count decreased (18.8%/10.1%) were more common in GC than GS in the low CCr group. In contrast, the incidence of all grade 3-4 non-hematological AEs was higher (36.0%/11.8%) in GS than GC in the low CCr group ( p = 0.0002). Conclusions: GS was better in terms of OS, PFS, and hematological toxicities than GC in the low CCr group. GS might be recommended for the population with lower renal function in the treatment for advanced BTC.
Impact of initial imaging with gallium-68 dotatate PET/CT on diagnosis and management of patients with neuroendocrine tumors (NETs): A sequential case series.
Authors: Kennecke Hagen F. , Raghu Preethi , Lin Bruce , Funk Gayle L. , Alseidi Adnan , Hubka Michal , Rosales Joseph G , Rocha Flavio G. , Lee Marie E. 
Published: January 2019

379 Background: Somatostatin analogue functional imaging with Ga-68 Dotatate PET/CT has demonstrated superiority in lesion detection in patients with NETs. The effect of this novel imaging modality on US clinical practice and its usefulness in different types of NETs is not well described. We describe the impact of initial NETSPOT imaging on diagnosis and management in NET patients at a large urban medical center. Methods: Consecutive patients diagnosed with NETs and referred to our institution who received an initial Ga-68 Dotatate PET/CT between 07/2017-09/2018 were included. Imaging was reviewed and compared to prior available CT, MRI, and/or In-111 Pentetreotide scans. Results: Among 101 patients, 51/50 were female/male, tumor origins were gastroenteropancreatic (GEP) (75%), Unknown Primary (UP) (13%), lung (8%), thymic (2%), and other (2%). All tumors were histologically well/moderately differentiated and 37/51/3/10 were G1/G2/G3/Unknown, respectively. Initial imaging with Ga-68 Dotatate PET/CT revealed additional metastatic disease in 37 of 77(48%) patients with prior evidence of metastatic disease. Most common sites were distant lymph nodes (18), bone (15) and liver (9), peritoneal/pleural (4). A previously UP tumor was identified in 3 patients. No patients with metastatic lung carcinoids (6 atypical, 2 typical) or thymic NETs (2 atypical/G2) NETs had evidence of Ga-68 Dota PET/CT uptake above reference liver SUV levels. Results of imaging altered patient management as follows: 14 initiated systemic therapy due to documentation of progression, in 6 surgical therapy was altered, in 4 biopsy/other management was changed. In 11 patients with no tumor Ga-68 Dotatate uptake, decisions about use of PRRT and somatostatin analogues was altered. Conclusions: In this series, Ga-68 Dotatate PET/CT altered diagnosis and management in 35/101 NET patients. Among GEP and UP NETs, Dotatate imaging diagnosed primarily new nodal, bone, liver and pleural/peritoneal metastases missed by other imaging modalities. Results support the routine use of Ga-68 Dotatate PET/CT in the care of patients with advanced and early stage NETS.