bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of lymphocyte-to-monocyte ratio on efficacy of sorafenib for recurrent hepatocellular carcinoma after curative resection.
Authors: Yokoo Hideki , Kamiyama Toshiya , Sugiyama Ko , Orimo Tatsuya , Shimada Shingo , Nagatsu Akihisa , Kamachi Hirofumi , Taketomi Akinobu 
Published: January 2019

367 Background: Sorafenib, an oral multikinase inhibitor, is approved for advanced hepatocellular carcinoma (HCC) treatment. Predictive biomarkers of sorafenib are needed due to its frequent adverse effect. Lymphocyte to monocyte ratio (LMR) has been reported as a prognostic or predictive biomarker of chemotherapy in cancer. However, clinical significance of LMR are unclear as predictive biomarker of sorafenib. To investigate the efficacy prediction value of LMR in patients who received sorafenib for recurrent HCC after curative resection. Methods: Clinicopathological data of 59 patients who received sorafenib for recurrent HCC after surgical treatment between 2009 and 2017 were retrospectively analyzed. Sorafenib was administered at a dose of 400mg or 800mg. Survival outcomes were estimated using the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate analyses were performed to evaluate the predictive impact of LMR and other clinicopathological factors for efficacy of sorafenib on overall survival (OS) and progression free survival (PFS). Results: The optimal cutoff value of LMR for response evaluation was 3.1, which resulted in the most appropriate sensitivity of 60.5% and specificity of 71.4%, with the area under the curve (AUC) of 0.641 (95% C.I.: 0.515-0.806). All patients were divided into either a low ( < 3.1) LMR (LLMR) group (n = 27), or a high ( > 3.1) LMR (HLMR) group (n = 32). Patients with HLMR group had significantly increased OS (MST: 20.0M vs 8.0M, P = 0.001) and PFS (MST: 10.2M vs 5.1M, P < 0.001) compared to those with a LLMR group. Multivariate analyses indicated that a HLMR was a significantly independent predictor of superior OS (P = 0.006) and PFS (P < 0.001). Conclusions: LMR in pre-administration of sorafenib was demonstrated to serve as an independent efficacy prediction factor of sorafenib in recurrent HCC patients after curative resection.
Phase Ib study of WNT inhibitor ipafricept (IPA) with nab-paclitaxel (Nab-P) and gemcitabine (G) in patients (pts) with previously untreated stage IV pancreatic cancer (mPC).
Authors: Dotan Efrat , Cardin Dana Backlund , Lenz Heinz-Josef , Messersmith Wells A. , O'Neil Bert , Cohen Steven J. , Denlinger Crystal S. , Shahda Safi , Kapoun Ann M. , Brachmann Rainer Karl , Uttamsingh Shailaja , Weekes Colin D. 
Published: January 2019

369 Background: The first-in-class recombinant fusion protein IPA blocks WNT signaling by binding WNT ligands, and in combination with Nab-P/G caused tumor regression in pt-derived PC xenografts. This open-label Phase 1b dose escalation study evaluated the combination of IPA with Nab-P/G in untreated mPC pts using a standard 3+3 design. Methods: Dose escalation in cohort 1 started with Nab-P 125 mg/m2 and G 1000 mg/m2 given on days 1, 8 ,15, with IV IPA (3.5 mg/kg) on days 1 and 15, in 28-day cycles. Due to fragility fractures seen in other studies with similar targeted agents, cohorts 2-4 were 6-pt cohorts treated with weekly Nab-P/G + IPA 3 mg/kg (cohort 2) or 5 mg/kg (cohorts 3 and 4) on day 1. These cohorts included strict bone marker monitoring and use of bisphosphonates as indicated. Based on pre-clinical data suggesting improved efficacy with sequential dosing, pts in Cohort 4 received IPA on day 1 followed by weekly chemotherapy starting on day 3 of 28-day cycles. Objectives included safety, maximum tolerated dose, recommended phase 2 dose, pharmacokinetics, immunogenicity, pharmacodynamics, and preliminary efficacy. Results: Twenty-six pts in four dose escalation cohorts were enrolled, five in the cohort one and seven each in cohorts 2-4. Median age was 61.7 years and a majority were male (73%). Reported IPA-related AEs of any grade occurring in ≥ 20% of pts included fatigue, nausea, vomiting, anorexia and pyrexia. IPA-related AEs grade ≥ 3 included 2 events of AST elevation, and 1 each of nausea, maculopapular rash, vomiting and WBC decrease. No dose limiting toxicities or fragility fractures were observed. Of 26 evaluable pts, 9 (34.6%) had a partial response and 12 (46.2%) stable disease, with clinical benefit rate of 80.8%. The study was closed due to termination of the program by the sponsor. At time of data cut off, median progression free survival was 5.9 months (95% CI 3.4-18.4), median overall survival was 9.7 months (95% CI: 7.0-14). One pt remains on therapy under compassionate use with ongoing response. Conclusions: IPA can be safely administered with Nab-P and G in pts with mPC. Additional studies targeting the WNT pathway in pancreatic cancer are warranted. Clinical trial information: NCT02050178.
Prospective trial of functional liver image-guided hepatic therapy (FLIGHT) with hepatobiliary iminodiacetic acid (HIDA) scans and update of institutional experience.
Authors: Long David Emmert , Huang Colin , Tann Mark , Dawson Benjamin , Bartlett Gregory , Maluccio Mary A. , Rhome Ryan , Kong Feng-Ming Spring , Ellsworth Susannah G. 
Published: January 2019

373 Background: Functional liver image-guided hepatic therapy (FLIGHT) is a novel stereotactic body radiation therapy (SBRT) planning technique. A functional map, generated from hepatobiliary iminodiacetic acid (HIDA) scans, is used to maximize the functional residual capacity of liver receiving < 15 Gy (FRC15HIDA). We present initial results of a prospective trial evaluating FLIGHT vs standard planning and update our institutional experience. Methods: Eligible patients were ≥ 18 yo with 1o or 2o liver malignancy and Child-Pugh ≤ B7. Liver function was assessed with HIDA and blood chemistry at baseline, mid-treatment, and 3, 6, and 12 months post SBRT. Both standard and FLIGHT (optimized to avoid high functioning liver) plans were generated for each patient. Treating MDs were blinded to planning technique before selecting the treatment plan. The primary endpoint was to show > 5% increase in FRC15HIDA in 3/15 pts. Secondary endpoints included the rate FLIGHT plans were selected and changes in HIDA and other liver function tests. Prior institutional experience included 27 pts with FLIGHT planned retrospectively. Paired t-test was used to compare dosimetric endpoints for FLIGHT vs. standard plans, including: FRC15HIDA, mean liver dose, effective uniform dose (EUD), and functional EUD (FEUD). Results: Fifteen pts were enrolled. The primary endpoint was met, as 4/15 pts had > 5% improvement in FRC15HIDA (mean 5.2%, range -2.3-19.8%). Notably, the FLIGHT plan was selected in 11/15. The mean improvements in FRC15HIDA (5.2 vs 5.0%), mean liver dose (11.9 vs. 13.0%), EUD (5.1 vs 5.2%), and FEUD (6.9 vs 7.1%) were similar between prospective and retrospective cohorts (p > 0.5). In the entire cohort (n = 42), FLIGHT improved FRC15HIDA, mean liver dose, EUD, and FEUD ( p ≤ 0.001). There were > 5% improvements in FRC15HIDA in 15, mean liver dose in 31, EUD in 19, and FEUD in 27. Conclusions: FLIGHT with HIDA led to improvements in all analyzed dosimetric parameters. The extent of benefit was similar in both cohorts, and there was individual variation in the extent of benefit. Longer follow-up is required to determine the effect of FLIGHT on post-SBRT liver function. Clinical trial information: NCT03338062.
An analysis of the safety and efficacy of rivaroxaban (Riv) and low molecular weight heparin (LMWH) in gastrointestinal cancer-associated venous thromboembolism (GICA-VTE).
Authors: Recio Boiles Alejandro , Veeravelli Sumana , Vondrak Jessi , Babiker Hani M. , Scott Aaron James , McBride Ali , Elquza Emad 
Published: January 2019

374 Background: CAVTE has a significant morbidity and mortality burden, with higher incidence and bleeding complications of anticoagulation (AC) in GICA. Current guidelines prefer LMWH, and recently added Riv, as an alternative standard after the SELECT-D trial (S-D). There is a paucity of data comparing the safety and efficacy of other DOACs in pts with GICA. We indirectly compared the safety and efficacy of Riv vs LMWH of our pts with active GICA-VTE at the University of Arizona Cancer Center (UACC) to the S-D GI-population. Methods: Pts with biopsy proven GICA, symptomatic or incidental VTE, and 6 months or more treatment with Riv or LMWH at UACC from 11/2013 - 12/2017 were retrospectively reviewed. S-D GICA data was extracted. Primary efficacy outcome was recurrent deep vein thrombosis (DVT), nonfatal pulmonary embolism (PE), or fatal PE. Safety outcomes for major bleeding (MB) include Hg drop ≥ 2 g/dL, transfusion of ≥ 2 units PRBC, bleeding in critical site, or bleeding contributing to death. Fisher exact test was used for p-value < 0.05. Results: Our review included pts on LMWH (n = 40), and Riv (n = 37) balanced population to the S-D trial. Recurrent VTE at 6mo was noted in 7.5% and 2.7% of pts, compared to S-D trial 11% and 4%, for LMWH and Riv respectively. MB at 6mo was 5% and 21.6% [p < 0.04] of pts, compared to S-D trial 5.8% and 8.7%, for LMWH and Riv, respectively. There was a non-significant difference [p > 0.07] between Riv and LMWH efficacy and safety beyond 6mo of AC. Conclusions: VTE secondary prophylaxis in GICA pts is complicated by high rates of recurrence and bleeding risk, DOACs provide another AC option. The most recent systemic review that included the two published DOACs RCTs for CAVTE [Hokusai and SELECT-D 2018], showed a higher incidence at 6-month of MB compared to LMWH RR: 1.74 (95% CI: 1.05–2.88) [Ang Li 2018], mainly driven by GICA. Our retrospective study showed a non-significant improved efficacy outcome although worse safety profile with Riv versus LMWH in GICA pts, by indirect comparison. Future RCTs with multi-center participation, particularly focused on GICA, can further provide information to guide safe and effective AC selection.
Outcome analysis of chemotherapy duration for resected stage I-II and unresected stage III pancreatic cancer.
Authors: Ma Sung Jun , Iovoli Austin J , Prezzano Kavitha M , Hermann Gregory , Serra Lucas M , Singh Anurag K 
Published: January 2019

375 Background: For resected early-stage pancreatic cancer, RTOG 9704 has evaluated the outcome of 3 weeks of adjuvant chemotherapy (C) followed by chemoradiation (CRT) and post-CRT C. For locally advanced pancreatic cancer, a recent literature review showed that the typical duration for induction C is between 1 and 6 months prior to CRT. The ideal duration of C prior to CRT remains unclear. This National Cancer Database (NCDB) study was performed to identify the optimal duration of C prior to CRT in patients with pancreatic cancer. Methods: The NCDB was queried for primary stage I-II, cT1-3N0-1M0, resected and stage III, cT4N0-1M0, unresected pancreatic adenocarcinoma treated with C+CRT (2004-2015). Cohorts I-II and III included stage I-II and stage III cases, respectively. In each cohort, the patients were stratified by the short (short C) and long duration (long C) of chemotherapy based on their median durations (70 and 90 days between the onset of chemotherapy and radiation for cohorts I-II and III, respectively). Baseline patient, tumor, and treatment characteristics were examined. The primary endpoint was overall survival (OS). Kaplan-Meier analysis, multivariable Cox proportional hazards method, and propensity score matching were used. Results: Among 1,577 patients, cohort I-II had 839 patients (n = 409 with short C, n = 430 with long C) and cohort III had 738 patients (n = 360 with short C, n = 378 with long C). Median follow-up was 39.5 months and 24.3 months for cohorts I-II and III, respectively. The long C group showed improved OS in the multivariable analysis in both cohort I-II (HR 0.72, p < 0.001) and cohort III (HR 0.83, p = 0.025). Using 1:1 propensity score matching, a total of 610 patients for cohort I-II and 542 patients for cohort III were matched. After matching, long C remained statistically significant for improved OS compared with short C in both cohort I-II (median OS 26.1 vs 21.9 months, p = 0.003) and cohort III (median OS 16.7 vs 14.2 months, p = 0.021). Conclusions: Our NCDB study using propensity score matched analysis showed a survival benefit in the use of longer duration chemotherapy compared to shorter duration chemotherapy for both resected stage I-II and unresected stage III pancreatic cancer.
Clinical characteristics and predictors of outcomes in patients with fibrolamellar carcinoma: An eleven-year analysis of the National Cancer Database (NCDB).
Authors: Assi Hussein , Hatoum Hassan , Mukherjee Sarbajit , Machiorlatti Michael , Vesely Sara , Pareek Vipul 
Published: January 2019

413 Background: Fibrolamellar carcinoma (FLC) is a very rare liver tumor, comprising only 1% of all primary liver tumors in the United Sates. There is no standard of care for unresectable disease. Current practices are based on small retrospective studies and case series. We aim to analyze the clinicopathologic factors and treatment modalities affecting overall survival (OS) in FLC. Methods: Using the National Cancer Data Base (NCDB), we identified 496 patients diagnosed with FLC between 2004 and 2015. Simple descriptive statistics were created for all covariates. Survival data was available on 461 patients. Kaplan Meier Survival analysis was used for unadjusted results, and Cox proportional hazards model was used for multivariable analysis. The objective of the study is to identify predictors of survival in FLC. Results: The median age at diagnosis was 32 (range 18-90) years. Fifty-six percent were males. Stage distribution included 114 (31.2%), 43 (11.8%), 89 (24.3%) and 120 (32.8%) patients for stages I, II, III and IV, respectively. Median follow-up was 24 months. Surgery of the primary site was performed on 282 (56.9%) of patients, 146 (51.2%) of which had regional lymph node dissection. Seventy (47.9%) patients had pN+ disease. Among patients with available serum alpha fetoprotein (AFP) data, 146 (42.5%) had abnormal AFP levels (> 20 ng/mL). Median OS by stage were 78.5, 87.2, 18.6, and 10.6 months for stages I, II, III, and IV, respectively. Multivariate analysis showed that age (HR 1.01, p < 0.0001), pN+ (HR 2.31, p = 0.0003), and abnormal AFP (HR 1.69, p = 0.0003) were negative predictors of survival. Among metastatic patients, 57 (11.4%) had metastatectomy. Metastatectomy improved overall survival in stage IV FLC, HR 0.51 (95% CI 0.29-0.89). Conclusions: Independent predictors of decreased OS in patients with FLC include age, pN+ and abnormal AFP. Metastatectomy improved OS. FLC is a rare disease entity that warrants further investigations to better delineate optimal treatment approaches.
SWOG S1505: Initial findings on eligibility and neoadjuvant chemotherapy experience with mfolfirinox versus gemcitabine/nab-paclitaxel for resectable pancreatic adenocarcinoma.
Authors: Sohal Davendra , McDonough Shannon , Ahmad Syed A. , Gandhi Namita , Beg Muhammad Shaalan , Wang-Gillam Andrea , Wade James Lloyd , Guthrie Katherine A , Lowy Andrew M. , Philip Philip Agop , Hochster Howard S. 
Published: January 2019

414 Background: Clinical outcomes after curative therapy of resectable pancreatic ductal adenocarcinoma (PDA) remain suboptimal. For early control of systemic disease with aggressive perioperative chemotherapy (CTx), we conducted a prospective trial in the National Clinical Trials Network (NCTN) setting. Methods: S1505 was a randomized phase II trial of periop (12 weeks pre-, 12 weeks post-op) CTx with either mFOLFIRINOX (5-fluorouracil, irinotecan, oxaliplatin – without bolus 5-FU and leucovorin; Arm 1), or gemcitabine/nab-paclitaxel (Arm 2). Eligibility required adult patients with ECOG PS 0 or 1, confirmed tissue diagnosis of PDA, and resectable disease: no involvement of the celiac, common hepatic, or superior mesenteric arteries (and, if present, variants); < 180° interface between tumor and vessel wall, of the portal or superior mesenteric veins; patent portal vein/splenic vein confluence; no metastases. Primary outcome is 2-year overall survival (OS), using a “pick the winner” design; for 100 eligible patients, accrual up to 150 patients was planned, to account for cases deemed ineligible at central radiology review. Results: From 2015 to 2018, 147 patients were enrolled; 74 to Arm 1; 73 to Arm 2. At central radiology review, 42/147 (29%) were ineligible; of these, 15 (36%) had venous involvement ≥ 180°, 22 (52%) had arterial involvement, 28 (67%) had distant disease. One patient had distal cholangiocarcinoma (ineligible); one withdrew consent after randomization. Eligible patients (n = 103) had median age 64 years; males 58%; whites 89%; PS 0 64%. Of 103, 99 (96%) started and 86 (83%) completed preop CTx. There was one death due to sepsis and 61 additional patients experienced grade 3/4 toxicities. To date, 76 of 99 (77%) patients went to surgery and 72 (73%) underwent resection. Conclusions: This is the first-ever NCTN study of periop CTx for resectable PDA. Accrual was brisk, establishing feasibility. Ineligible cases after central radiology review highlight quality control and physician education imperatives for neoadjuvant PDA trials. Preop CTx safety and resection rates are encouraging. Follow up for OS is ongoing. Clinical trial information: NCT02562716.
Outcomes following liver SBRT for metastatic pancreatic cancer.
Authors: Oladeru Oluwadamilola Temilade , Vaios Eugene J , Eyler Christine , Noe Bridget N. , Fernandez Del-Castillo Carlos , Weekes Colin D. , Ferrone Cristina , Lillemoe Keith D , Qadan Motaz , Parikh Aparna , Clark Jeffrey W. , Ryan David P. , Allen Jill N , Hong Theodore Sunki , Wo Jennifer Y 
Published: January 2019

418 Background: Traditionally, the role of localized therapy for metastatic pancreatic cancer (MPC) has been limited. However, with more effective systemic therapies, recent studies have explored a potential role for local therapies. We aimed to report outcomes following SBRT (stereotactic body radiation therapy) for liver metastases (LM) in setting of MPC and to identify predictors of response. Methods: 41 patients who underwent ablative RT to LM for MPC (2005-17) were retrospectively identified. Median RT dose was 50 Gy (range: 8-60 Gy), delivered in 5-6 fractions. Kaplan Meier method was used to calculate local control (LC), progression-free survival (PFS) and overall survival (OS). Univariate (UVA) and multivariate (MVA) Cox proportional hazards models were used to identify predictors of clinical outcomes. Results: Median follow up was 14.6 months. This cohort included 19 men and 22 women. 61% of pts had metachronous LM, 39% had synchronous LM. At time of RT, the treated lesion was stable /responding to chemotherapy (CTX) in 36.6% of pts; 46.3% were progressing with mixed response; 17% were off/refused CTX. Median number of prior CTX regimens was 2 (range: 0-5). Median number of LM was 1 (range: 1-4). Median pre-RT CEA was 7 ng/mL, median pre-RT CA19-9 was 354 U/ml. The 12-month outcomes were 75.8% LC, 16.5% PFS, and 36.3% OS. 8/41 (20%) patients were off CTX for ≥ 4 months. On UVA for LC, pre-RT CA19-9 (log10 scale) was associated with LC (HR 2.28, p = 0.03). Timing of LM, CTX response of LM, number of lesions, RT dose and CEA did not predict LC. On UVA for PFS, extrahepatic disease at time of RT was associated with worse PFS (HR: 2.47, p = 0.04), and response to CTX (progressive vs. stable/responding) approached significance (HR 1.83, p = 0.10). On UVA for OS, lower pre-RT CEA (HR 1.009, p = 0.03), lower pre-RT CA19-9 (HR 1.67, p = 0.01), and response to CTX (HR 6.42, p < 0.001) were associated with improved OS. On MVA for OS, response to CTX at time of liver RT remained significant for OS. Conclusions: SBRT of LM for MPC offers high rate of LC. In a small subset of patients, SBRT to LM may offer prolonged duration off systemic therapy. Lower pre-RT CA 19-9 and CEA, absence of extrahepatic disease, and stability/response of CTX at time of liver RT may select for patients most likely to benefit.
A phase I/II study of RX-3117, an oral antimetabolite nucleoside, in combination with nab-paclitaxel (nab-pac) as first-line treatment of metastatic pancreatic cancer (met-PC): Preliminary results.
Authors: Babiker Hani M. , Schlegel Peter J. , Hicks Lee G. , Bullock Andrea J. , Burhani Nafisa , Benaim Ely , Peterson Christine , Heaton Callie , Ocean Allyson J. 
Published: January 2019

420 Background: RX-3117 is an oral small molecule antimetabolite, cyclopentyl pyrimidyl nucleoside that is activated by cancer-enriched uridine cytidine kinase 2. Single agent RX-3117 has demonstrated efficacy in a phase III single agent clinical study of RX-3117 in met-PC and bladder cancer. RX-3117 in combination with nab-pac is being evaluated as first line treatment of met-PC cancer. Methods: This is a multicenter, open label phase I/II study (NCT03189914). Eligible subjects (aged ≥ 18 years) have histologically or radiologically proven met-PC with no prior therapies for metastatic disease, ECOG PS 0-1, and normal lab values. phase I identified the MTD dose that is being further evaluated in the phase II: RX-3117 (700 mg administered orally once-daily for 5 consecutive days with 2 days off per week) and nab-pac (125 mg/m2 administered once weekly) for 3 weeks with 1 week off per 4-week cycle. The Safety Committee reviewed data from phase I before moving to phase II. The primary endpoint of phase II (dose expansion) is an adequate number of responders based on PFS at 4 months and/or objective clinical response per RECIST v1.1. Results: As of September 21, 2018, 8 phase I subjects and 13 phase II subjects were enrolled and treated (9 males and 12 females, median age 67 years). The most common (≥ 15%) related adverse events were nausea, diarrhea, fatigue, alopecia, decreased appetite, rash, vomiting, and anemia. Fourteen subjects had at least one on-study scan (after 2 cycles). One subject experienced a complete response (CR) after 6 cycles of therapy with normalization of CA19.9 (-76%). Three subjects exhibited a partial response (PR): two after 2 cycles (39-47%) and one after 4 cycles of therapy (36%). Eight subjects had stable disease for at least 2 months, and 4 subjects had PFS of at least 4 months. The disease control rate (CR+PR+SD) was 86% in evaluable subjects while the overall response rate (CR+PR) was 29%. Conclusions: RX-3117 in combination with nab-pac appears to be safe and well tolerated in subjects with met-PC. Antitumor activity per RECIST was observed in 12 subjects. Phase II of the clinical study is currently ongoing. Clinical trial information: NCT03189914.