bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized controlled trial to compare the effectiveness between surgery and radiofrequency ablation for hepatocellular carcinoma: SURF trial.
Authors: Hasegawa Kiyoshi , Kokudo Norihiro , Matsuyama Yutaka 
Published: March 2017

TPS506 Background: Which is superior to treat hepatocellular carcinoma (HCC), surgery or percutaneous ablation? This has been one of the most important questions in clinical research of hepatology. However, it has long remained unanswered because it is difficult to approach, as we mentioned previously (Ann Surg 2008;247:557-8). Thus, in 2009, we started this multicenter study in Japan to reach a strong conclusion to the above question (UMIN:000001795). Methods: The major inclusion criteria are: tumor foci numbering three or fewer, and each measuring 3 cm or less); Child–Pugh score of 7 or less; aged between 20 and 79 years; and indications for either surgical resection or radiofrequency ablation (RFA), as described previously (Hepatol Res 2010;40:851-2). In the study design, we adopted two co-primary end-points: overall survival (OS) and recurrence-free survival (RFS). If assuming 3-year RFS following surgery and RFA are assumed as 45% and 35%, respectively, 600 cases are regarded as necessary. Because 600 cases would be also sufficient to detect 10% difference in OS, the target number of cases was set as 600. However, the recruitment was very difficult. The Independent Data Monitoring Committee recommended us to transiently stop the recruitment at the end of August 2015 when the number of the registered cases reached 308. At submission of this abstract, we are considering whether the current number (308) is enough or not to detect 10% difference in RFS by calculating conditional predictive power. We will describe the trial design, and the current situations in detail for debate. Clinical trial information: UMIN:000001795.
Phase Ib/II study of ALT-803 in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer.
Authors: Acoba Jared David , Rock Amy , Wong Hing C. 
Published: March 2017

TPS510 Background: IL-15 is one of the most promising new candidates in cancer immunotherapy. Similar to IL-2, IL-15 stimulates natural killer (NK) and CD8+ T cells, however IL-15 may be a more effective and safer therapy as it does not trigger regulatory T cells or induce capillary leak syndrome. Preclinical data also show that IL-15 is effective in eradicating murine pancreatic cancers. However, the use of rhIL-15 in the clinic however has been limited by its short half-life (30 minutes) and cytokine related adverse effects, such as fever and hypotension. Compared with IL-15, ALT-803, a novel IL-15 superagonist complex (IL-15N72D:IL-15RαSu/Fc), has a prolonged serum half-life and is capable of potently inducing NK and CD8+ T cell proliferation in vivo. Pancreatic cancer remains one of the most common causes of cancer death and novel therapies are needed. This study represents the first clinical experience of ALT-803 in the treatment of pancreatic cancer. Methods: This is a Phase Ib/II, multi-institution study of ALT-803 in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer. The study involves a phase Ib dose escalation phase to determine the MTD using a standard 3+3 design. Patients will receive gemcitabine 1,000 mg/m2 and nab-paclitaxel 125 mg/m2 D1, 8, 15 and ALT-803 at assigned dose on D2, 9, 16 of a 28d cycle. Primary endpoints are safety and tolerability. Phase II will be a two-stage expansion phase using a Simon two-stage design with a primary endpoint of survival at 8.5 months. Secondary endpoints include response rate, progression free survival, and overall survival. Response will be assessed q8 weeks by RECIST v1.1. Major inclusion criteria include: locally advanced (Phase Ib only) or metastatic pancreatic adenocarcinoma, adequate organ function, PS ECOG 0-2, and 0 or 1 (Phase Ib only) line of prior therapy for advanced pancreatic cancer. Prior nab-paclitaxel is not allowed Current enrollment: Enrollment to the first dose level is ongoing. Complete accrual of phase Ib is expected within nine months. Clinical trial information: NCT02559674.
A phase II pilot trial of nivolumab + albumin bound paclitaxel + paricalcitol + cisplatin + gemcitabine (NAPPCG) in patients (pts) with previously untreated metastatic pancreatic ductal adenocarcinoma.
Authors: Borazanci Erkut Hasan , Jameson Gayle S. , Borad Mitesh J. , Ramanathan Ramesh K. , Korn Ronald Lee , Caldwell Lana , Ansaldo Karen , Hendrickson Kristin , Von Hoff Daniel D. 
Published: March 2017

TPS511 Background: Despite decades of basic and clinical research, effective therapy for the treatment of patients with pancreatic ductal adenocarcinoma (PDAC) remains one of the greatest unmet clinical needs in oncology today. Albumin-bound paclitaxel (AP) and gemcitabine (G) reported on an improvement in overall survival in metastatic (m) PDAC [NEJM 2013; 369:1691-1703]. The addition of cisplatin (C) has shown promising clinical data in previously reported studies [Cancer Res 2015; 75(15 Suppl):Abstract nr LB-003]. Through further preclinical work, vitamin D analog therapy decreases myeloid derived suppressor cell (MDSC) and regulating T cells (Tregs) thus turning PDAC into a more immune friendly microenvironment. This trial combines AP/C/G with the vitamin D analog paricalcitol (P) and the antibody-PD-1 drug Nivolumab (N) as a combination therapy for individuals with previously untreated metastatic PDAC. This trial evaluates the efficacy and safety of NAPPCG in patients in that population (NCT02754726). Methods: Key eligibility criteria include Stage IV PDAC, no prior chemotherapy for systemic disease, KPS ≥ 70; life expectancy ≥ 12 weeks and measurable disease. Key exclusion criteria include prior PD-1 or PD-L1 therapy. Doses are AP 125 mg/m2 undiluted, G 1000 mg/m2 in 500 ml of normal saline (NS), each infused over 30 minutes with C 25mg/ m2 in 500 ml of NS infused over 60 minutes on days 1, 8, 22, and 29 of a 42 day cycle. N is given at a fixed dose of 240 mg as a 60 minute infusion on days 1, 15, and 29. P is given at a fixed dose of 25 µg IV on days 1,4,8,12,15,22,26,29,32,36,and 39. Primary objective is to determine the efficacy of the combination NAPPCG for patients with previously untreated metastatic PDAC through determining CR, ORR, PFS, and OS. The secondary objective is to evaluate the safety of NAPPCG in patients with previously untreated metastatic PDAC. The study initiated accrual in April of 2016. If 4 of the first 10 patients are determined to have a PR the trial will expand to a total of 25 patients. Clinical trial information: NCT02754726.
Phase I study of definitive chemoradiation with gemcitabine and the WEE1 inhibitor AZD1775 in unresectable pancreatic cancer.
Authors: Cuneo Kyle Clifford , Morgan Meredith , Schipper Matthew J , Maybaum Jonathan , Al-Hawary Mahmoud , Simeone Diane M. , Sahai Vaibhav , Zalupski Mark , Lawrence Theodore Steven 
Published: March 2017

TPS512 Background: Targeting cell cycle checkpoints has the potential to enhance the efficacy of chemoradiation therapy. Tumor cells commonly have an abnormal G1 checkpoint due to mutations in the p53 pathway making them reliant on the G2 checkpoint to repair DNA damage. In our preclinical studies, WEE1 inhibition with AZD1775 abrogates the G2 checkpoint and sensitizes pancreatic cancer cell lines and xenografts to chemoradiation. Additionally, AZD1775 attenuates homologous recombination repair and promotes replication stress in cancer cells. Given our preclinical findings, we designed a phase I dose escalation study of the WEE1 inhibitor AZD1775 with gemcitabine and radiation in patients with unresectable pancreatic cancer (NCT02037230). Methods: The primary objective of our phase I study is to determine the MTD (maximum tolerated dose) of AZD1775 when combined with gemcitabine and radiation in patients with locally advanced pancreatic cancer. Our secondary objectives are to estimate the efficacy of this regimen at the target dose and to determine if WEE1 is inhibited by AZD1775 at or below its target dose in surrogate tissues (hair follicles). Patients with unresectable, non-metastatic pancreatic cancer are eligible for the study. Protocol therapy consists of the administration of AZD1775 and gemcitabine at the assigned dose levels in accordance with a Time-to-Event Continual Reassessment Method. All patients on the study are treated with four cycles of therapy consisting of AZD1775 given orally on days 1, 2 and 8, 9 of a 21 day cycle with gemcitabine given intravenously over 30 minutes on day 1 and day 8. Cycles 2 and 3 are administered with concurrent radiation therapy, 52.5 Gy in 25 fractions to the primary pancreatic tumor. The MTD will be determined by the development of dose limiting toxicities (DLT) within the first 4 cycles of therapy with a target DLT rate of 25%. Blood samples obtained at baseline and after cycles 1, 2, and 4 will be used for correlative studies on circulating tumor cells and tumor derived exosomes. Our estimated accrual is 36 patients. To date we have enrolled 21 patients. Supported by P50 CA130810, R01 CA163895, Cancer Center Core grant P30 CA46592, and the Taubman Institute. Clinical trial information: NCT02037230.
A single arm, prospective multicenter phase II study FOLFIRINOX in patients with advanced and recurrent biliary tract cancer.
Authors: Takahara Naminatsu , Isayama Hiroyuki , Nakai Yousuke , Ioka Tatsuya , Kanai Masashi , Sasaki Takashi , Furuse Junji , Koike Kazuhiko 
Published: March 2017

TPS514 Background: The current standard of care for patients with advanced biliary tract cancer (BTC) is gemcitabine and cisplatin (GC) combination chemotherapy. Despite intensive researches, no trials have proved better overall survival (OS) over GC. Recently, FOLFIRINOX provided a remarkable survival benefit over gemcitabine in patients with metastatic pancreatic cancer. Given the promising results of FOLFIRI and FOLFOX in patients with advanced BTC, FOLFIRINOX can be an attractive option in patients with advanced BTC as well. Methods: This is a single-arm, open-label, multi-center phase II study to evaluate the safety and efficacy of FOLFIRINOX in patients with advanced BTC. The major inclusion criteria are as follows; unresectable or recurrent BTC, histologically or cytologically confirmed adenocarcinoma, no prior chemotherapy or radiation therapy, age of 20-75 years, an ECOG PS of 0 or 1, at least one measurable lesion, adequate hematological, liver and renal function. The major exclusion criteria are as follows; UGT genetic polymorphisms of homozygous UGT1A1*6 or *28 or heterozygous UGT1A1*6 and *28, massive pleural effusion or ascites. FOLFIRINOX consists of oxaliplatin of 85 mg/m2, irinotecan of 180 mg/m2, leucovorin of 400 mg/m2 administered by intravenous infusion and fluorouracil of 400 mg/m2 by intravenous bolus and of 2,400 mg/m2 by continuous intravenous infusion every 2 weeks. The primary outcome is progression-free survival (PFS), and the secondary outcomes are OS, tumor response and safety. PFS and OS will be calculated from the date of enrollment until the date of documentation of disease progression or death in patients without disease progression and the date of death. Tumor response will be evaluated according to the RECIST version 1.1 every 2 months. Safety will be evaluated with the CTCAE version 4.0. A total of 35 patients will be required to provide 75% power to detect an increase in median PFS from 6 months provided by standard care of GC to 10 months in patients receiving FOLFIRINOX, with a 24 months of recruitment and 18 months of follow-up. A phase III trial will be considered when this study shows the lower limit of the 80% confidence interval for PFS is longer than 6 months. Clinical trial information: UMIN000020801.
A phase II trial of neoadjuvant chemotherapy with GSL (GEM+TS-1+LV) for marginally resectable pancreatic cancer.
Authors: Sakamoto Yoshihiro , Isayama Hiroyuki , Saito Kei , Arita Junichi , Nakai Yousuke , Hasegawa Kiyoshi , Watadani Takeyuki , Aoki Taku , Koike Kazuhiko , Kokudo Norihiro 
Published: March 2017

TPS516 Background: The impact of neoadjuvant chemotherapy (NAC) for borderline resectable pancreatic cancer is under debate. In this context, a phase II trial of neoadjuvant chemotherapy for marginally resectable pancreatic cancer is undergoing since Jan 2014 (UMIN000012480). In this trial, we employed GSL regimen (Gemcitabine 1000mg/m2, TS-1 80mg/m2, LV 50mg) which have reported favorable results (33% of response rate, 93% of disease control rate and 16.6 months of overall survival) for unresectable pancreatic cancer (Cancer Chemother Pharmacol 2014; 74:911). Methods: The subjects were marginally resectable, pathologically proven pancreatic cancer, which consists of borderline resectable because of arterial attachment (BR-A) and locally advanced or unresectable (LA, UR) with short-segment ( = / < 3cm) arterial abutment based on NCCN guideline 2015. At least two surgeons, two medical oncologists, and one radiologist joined a consensus meeting to decide the indication of NAC and evaluated the efficacy of NAC every month. Patients with CR, PR or SD for 2-6 months underwent curative surgery combined with dissection of the nerve plexus around major arteries. The primary endpoint was R0 resectional rate, and the secondary endpoints were resectional rate, response rate, adverse effect, surgical morbidity, mortality, operative time and hospital stay period. Twenty-four patients are going to be enrolled, and 23 patients have undergone enrollment of NAC at the time of submission of the present abstract. Clinical trial information: 000012480.
Clinical utility of quasimonomorphic variation range (QMVR) on the determination of microsatellite instability (MSI) status in Japanese patients (pts) with colorectal cancer (CRC): GI-SCREEN-CRC-MSI sub-study 01.
Authors: Bando Hideaki , Okamoto Wataru , Fukui Takafumi , Yamanaka Takeharu , Akagi Kiwamu , Yoshino Takayuki 
Published: March 2017

TPS808 Background: The current analysis for the determination of Microsatellite Instability (MSI) status in tumor requires matched normal DNA as a reference. The Promega MSI panel included five monomorphic markers (NR-21, BAT-26, BAT-25, NR-24, and MONO-27) which were known to have few variant alleles in Caucasian as well as Japanese. Therefore, these markers might be able to determine the MSI status without matched normal DNA, although it is conceivable that Quasi-Monomorphic Variation Range (QMVR) in each ethnic group could be different. In our pilot study, the QMVR in 149 Japanese healthy individuals were 98.4-104.4 base pair (bp) in NR-21, 111.4-117.4 bp in BAT-26, 121.0-127.0 bp in BAT-25, 129.5-135.5 bp in NR-24, and 149.9-155.9 bp in MONO-27, respectively. Methods: This clinical evaluation study is to establish the QMVR in Japanese colorectal cancer (CRC) patients (pts) and to evaluate the clinical utility of the QMVR on the determination of MSI status without matched normal DNA. The primary endpoint is the concordance of MSI status between the standard method using DNA from tumor plus matched normal samples and testing method using DNA from only tumor samples. The new MSI kits including the Promega MSI panel were manufactured under the Quality Management System (QMS) for in vitro diagnostics (IVDs). As the decision algorithm, tumors exhibiting 2 or more markers outside the QMVR were classified as MSI-High, cases with 1 marker outside the QMVR were classified as MSI-Low, and those without any marker outside the QMVRs were classified as microsatellite stable (MSS). Planned enrollment will be 400 pts. Clinical trial information: UMIN000024144.
A randomized phase II study to investigate the deepness of response (DpR) of FOLFOXIRI plus cetuximab (Erbitux) versus FOLFOXIRI plus bevacizumab as the first-line therapy in metastatic colorectal cancer (mCRC) patients with RAS wild-type tumors: DEEPER.
Authors: Tsuji Akihito , Sunakawa Yu , Ichikawa Wataru , Kubota Yutaro , Kochi Mitsugu , Sekikawa Takashi , Sagawa Tamotsu , Kotaka Masahito , Nakamura Masato , Shimada Ken , Masuishi Toshiki , Satake Hironaga , Yabuno Taichi , Yoshida Taichi , Goto Masahiro , Ota Hirofumi , Okita Yoshihiro , Takeuchi Masahiro , Fujii Masashi , Nakajima Toshifusa 
Published: March 2017

TPS818 Background: The FIRE-3 study proved that early tumor shrinkage (ETS) and DpR were superior with FOLFIRI plus cetuximab (cet) compared to bevacizumab (bev) in mCRC patients with RAS wild-type tumors (Stintzing S, et al. Lancet Oncol 2016). A retrospective analysis of treatment groups between FOLFOXIRI plus anti-EGFR antibody and bev showed significantly better DpR and ETS in the anti-EGFR antibody group (48.6% vs. 37.8% for the median DpR; 40.8% vs. 26.4% for the median ETS)(Salvatore L, et al. ESMO 2014). However, there have been few studies comparing cet with bev in combination with the FOLFOXIRI regimen used as a platform. Therefore, it is great interest to investigate whether cet will be more beneficial than bev when combined with the triplet regimen as a promising treatment option. Methods: Key eligibility criteria are as follows: histologically proven unresectable metastatic/recurrent CRC; RAS wild-type tumors; patients who have not received any prior chemotherapies or patients with relapse after at least 12 months following adjuvant chemotherapy. Primary endpoint of this study is the DpR until progression. Key secondary endpoints are the ETS at Week 8, progression-free survival, overall survival, and safety. After randomization, patients receive up to 12 cycles of FOLFOXIRI (irinotecan: 150 mg/m2, oxaliplatin: 85 mg/m2, l-levofolinate: 200 mg/m2, continuous fluorouracil: 2400 mg/m2, every two weeks) plus cet (initial: 400 mg/m2, subsequent: 250 mg/m2, weekly) or bev (5 mg/kg, every two weeks) as induction treatment. Thereafter, fluorouracil, l-levofolinate, and cet or bev are administrated as maintenance treatment. Based on previous reports, the difference of 12.5% in the median DpR between the cet and bev groups was assumed. Each standard deviation was estimated to be 42% (cet group) and 34% (bev group). Under the conditions of significance level of 0.05 for a two-sided test and power of 0.85, the required sample size was calculated to be 360 patients. Thirty-three patients have been enrolled by August 2016. Clinical trial information: 000018217.
Prevention of lymphedema in women with breast cancer (BC): Results of CALGB (Alliance) 70305.
Authors: Paskett Electra D. , Le-Rademacher Jennifer , Oliveri Jill , Liu Heshan , Seisler Drew K. , Sloan Jeffrey , Armer Jane M. , Naughton Michelle Joy , Hock Karen , Schwartz Michael A. , Unzeitig Gary Walter , Padula Gilbert D. A. , Grubbs Stephen S. , Yee Lisa , Bailey Lisa , Willey Shawna C. , Sunnenberg Thomas Dean , Baddi Lisa L. , Fleming Gini F. ,   CALGB 70305 Investigators
Published: March 2017

104 Background: Lymphedema (LE), a side effect of BC treatment, affects 8%–56% of women. The study tested the effectiveness of an education only vs education + exercise intervention on LE incidence in a group randomized trial (NCT00376597) of 38 cooperative group sites. Methods: Newly diagnosed women with stage I-III BC were consented and arm circumference and range of motion were measured pre-surgery. After surgery, patients (pts) were enrolled based on the randomization assignment of their treating institution, stratified by their type of node dissection (sentinel or axillary), and received either: education only: its causes, signs, symptoms and risk reduction strategies, or education + personalized exercise instruction from a physical therapist, with elastic compression garments to wear during heavy arm use and air travel. Pts completed surveys and arm measurements at baseline (BL), 12 and 18 months with the LE endpoint defined as ≥ 10% difference in limb volume at any time from BL to 18 months or physician diagnosis of LE. Cochran-Mantel-Haenszel (CMH) tests were used to compare the LE-free rate between arms, adjusted for type of biopsy. Logistic regression assessed predictors of LE. Results: 568 pts were enrolled, 45% in education only, and 55% in education + exercise, with 554 (98%) included in the analyses. Pts were on average 57.7 years, White (83%), non-Hispanic (92%) and married (62%). 47% only had sentinel node dissection, 35% had mastectomy, and 37% had chemotherapy. The LE-free rate was 58% in education only vs 55% in education + exercise (CMH p = 0.73). Predictors of LE included surgery type (lumpectomy vs mastectomy, OR = 2.22, p < 0.001) and chemotherapy (no vs yes, OR = 1.73, p = 0.02), after adjusting for BMI and type of node dissection. Only one-third wore the sleeve at least 75% of the time and only 50% did LE exercises at least weekly. Conclusions: There was no difference by intervention arm in LE incidence by 18 months. Poor adherence in the education + exercise arm may have been a factor. Additional analyses will assess quality of life, body image and knowledge about LE by arm. Further research is needed to effectively prevent LE in pts after BC surgery. Research Support: UL1TR001409; U10CA037447, UG1CA189823 Clinical trial information: NCT00376597.
Fertility preservation and decisional regret in young breast cancer survivors: A longitudinal analysis.
Authors: Dewald Samantha Rose , Natarajan Loki , Su Irene 
Published: March 2017

106 Background: Fertility is important to many young breast cancer survivors (YBCS), who face difficult decisions on whether to undergo fertility preservation prior to treatment. Because few longitudinal data assessing decisional regret are available, the objectives of this study were to assess longitudinal changes in decisional regret on fertility preservation following breast cancer diagnosis; determine if fertility preservation treatment decisions are related to decreased decisional regret. Methods: From 3 academic breast cancer programs, 169 YBCS younger than age 45 were recruited at diagnosis between 2009 and 2012 and followed prospectively for ovarian function. Participants completed questionnaires on fertility preservation choices and the Decisional Regret Scale (DRS) during study visits every 6 months for up to 5 years. DRS is scored 0 (no regret) to 100 (highest regret). DRS was dichotomized as none versus any decisional regret. Generalized linear models estimated the change in DRS over time and the association between patient characteristics and DRS. Results: Mean age at diagnosis was 38.7 (SD 4.8). Median total follow-up was 176 days (IQR 84 to 1415 days). Enrollment DRS was available for 89 women; 48% reported decisional regret about fertility preservation (median DRS=20). Participants worried about future fertility were more likely to report decisional regret (p=0.009). 31% underwent fertility preservation, but this was not associated with decisional regret (p=0.65). In repeated measures analysis for the entire cohort, no significant change in DRS occurred over this time period (OR 0.8, 95% CI 0.4-1.7). Worry about future fertility remained significantly associated with DRS over time (OR 55.1, 95% CI 7.7-395.1). Conclusions: In a cohort of YBCS, experiencing decisional regret about fertility preservation persists for years after diagnosis. Those worried about future fertility are more likely to experience decisional regret regarding fertility preservation.