bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction FOLFIRINOX followed by chemoradiation with capecitabine for unresectable locally advanced pancreatic cancer (LAPC): Preliminary data.
Authors: Carvalho Rafael Ferreira de , Gil Erlon , Moreira Raphael Brandao , Peixoto Renata D'Alpino , Amarante Marcus Paulo Fernandes , Zanuncio Pedro , Ferrigno Robson , Moraes Paulo , Maluf Fernando C. , Buzaid Antonio C. , Cruz Marcelo Rocha De Sousa 
Published: February 2017

458 Background: FOLFIRINOX was found to have higher response rates and overall survival (OS) compared to gemcitabine-based regimens in the metastatic setting. However, the contribution of chemoradiotherapy to outcomes after FOLFIRINOX in LAPC remains uncertain. We aim at evaluating our experience with FOLFIRINOX followed by chemoradiation (IMRT) with capecitabine for patients with LAPC. Methods: Patients with unresectable LAPC who received induction FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan and oxaliplatin) followed by chemoradiation with capecitabine at our institution were screened and accrued at the time of radiotherapy and are being followed prospectively. Radiation technique consisted of IMRT with simultaneous integrated boost (SIB) - dose of 45 Gy (1.8Gy/day) to high-risk lymph nodes and 55 Gy (2.2Gy/day) to the primary tumor. Progression-free survival (PFS) and OS were estimated by the Kaplan-Meier method. Results: Fourteen patients (58% female) were included in the analyses. Median age at diagnosis of LAPC was 61 years (range 38-78). Median number of FOLFIRINOX cycles was 11 (range 4-13). With a median follow up fo 11.7 months, 43% of the patients have died. Median PFS and OS were 15.9 (95% CI 6.8 – 25.1) and 16.7 months (95% CI 10.9 – 22.4), respectively. There were no treatment-related deaths. Conclusions: Our data suggest that sequential treatment with FOLFIRINOX followed by chemoradiation with capecitabine is feasible and may offer promising PFS and OS among selected patients with LAPC. Randomized trials are urgently needed to assess the role of sequential treatment in this population.
Early radiotherapy versus late radiotherapy after incomplete transarterial chemoembolization in hepatocellular carcinoma.
Authors: Kim Mi Sun , Kim Do Young , Han Kwang-Hyub , Won Jong Yun , Lee Do Yun , Seong Jinsil 
Published: February 2017

459 Background: To investigate the efficacy of early RT (ERT) in comparison to late RT (LRT) in HCC patients after incomplete TACE. Methods: Between January 2006 and December 2011, 99 BCLC B and C stage HCC patients were reviewed. We defined ERT as curative aimed additional RT after the first TACE, and LRT was defined as salvage aimed additional RT for recurrent or re-growing remnant tumors after repeated TACE. The median prescribed dose was 45 Gy (range, 21.6 Gy–60 Gy) given in daily dose of 1.8 Gy–3 Gy. Three-dimensional conformal RT or intensity modulated RT was used for all patients. The in-field tumor response rate (IFTR) was evaluated using the modified response evaluation criteria in solid tumors. Results: Fifty eight (58.6%) patients received ERT and 41 (41.4%) patients received LRT. All patients had BCLC B-C stage HCC and the characteristics between two groups were not different significantly. However, vessel invasion was observed more often in the LRT group (p=0.039). The median interval between last TACE and RT was 2weeks in the ERT group, and 4 weeks in the LRT group. The IFTR at one month and three months were significantly higher in the ERT group. The one-year in-field progression-free survival rates were 79.5% and 45.9% in the ERT and LRT groups, respectively (p=0.007).The one-year overall survival rates were 75.9% and 48.8% in the ERT and LRT groups, respectively (p = 0.01). In the multivariate analysis, vessel invasion and treatment group (ERT vs.LRT) were independent predictor of OS (p=0.039 and p=0.035). PVTT and treatment group (ERT vs.LRT) showed correlation with IFPFS in the multivariate analysis (p=0.002 and p=0.01). Conclusions: While this finding may reflect differences in biological characteristics between the two groups, ERT within 2weeks after incomplete TACE should be considered.
An investigation of the safety of continued treatment with sorafenib in patients with unresectable hepatocellular carcinoma after the first disease progression: Multicenter, open-label, phase II safety study.
Authors: Akutsu Noriyuki , Sasaki Shigeru , Takagi Hideyasu , Kaneto Hiroyuki , Yonezawa Kazuhiko , Yawata Atsushi , Adachi Takeya , Yokoo Hideki , Kamiyama Toshiya , Hamamoto Yasuo , Shinomura Yasuhisa 
Published: February 2017

462 Background: Randomized studies showed that sorafenib significantly improved outcome in patients with unresectable hepatocellular carcinoma (HCC). However, there is no clear evidence to support the safety and benefit of continued treatment of sorafenib beyond disease progression (PD) in patients with HCC treated with sorafenib. We prospectively evaluated the safety and efficacy of sorafenib beyond PD in patients with HCC whose disease has progressed after first-line treatment with sorafenib. Methods: Unresectable HCC patients with evaluable lesion were treated with sorafenib until 1st PD, followed by soafenib until 2nd PD. The primary endpoint of the study was the safety after 1st PD until 2nd PD. Secondary endpoints of the study were response rate (RR), disease control rate (DCR), time to first PD (TTP1), time to second PD during continued treatment (TTP2), overall survival (OS), and safety throughout the treatment period. Adverse event was evaluated as per The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was evaluated as per Modified Response Evaluation in Solid Tumors (mRECIST) criteria. The Kaplan–Meier method was used to determine TTP and OS. Results: Of 30 patients enrolled from 6 sites in Japan, 29 patients received sorafenib treatment, and one patient refused chemotherapy. Twenty patients continued sorafenib beyond PD. Grade 3/4 adverse events occurred less frequently during TTP2 than during TTP1. No critical events related to sorafenib were reported during TTP2. In the first-line therapy, 29 patients treated with sorafenib showed RR of 10.3%, DCR of 60.7% and median TTP1 of 102 days. Twenty patients who received continued sorafenib beyond PD and showed RR of 0%, DCR of 45%, and median TTP2 of 77 days. Median survival time was 306 days. Conclusions: Sorafenib beyond PD had acceptable tolerability and considerable efficacy. In the present conditions without second line treatment, sorafenib beyond PD might be one of the treatment options. Clinical trial information: UMIN000005818.
Video-assisted thoracoscopic transdiaphragmatic liver resection for malignant tumors located in the posterosuperior segments.
Authors: Sunahara Masao , Kurauchi Nobuaki , Tsunetoshi Yusuke , Sawano Takeyuki , Kasajima Hiroyuki , Hara Yutaka , Suzuki Shinsaku , Toyama Shigeru , Kimura Jun 
Published: February 2017

469 Background: Laparoscopic liver resection has recently become more common. However, it is difficult to resect laparoscopically the liver tumor located in the posterosuperior segments (IVa, VII and VIII), especillay for patients with liver cirrhosis. Compared to laparoscopy, gaining access to tumors in the dome of the liver may be more easily obtained via thoracoscopy.Therefore, we describe the technique and outcome of a video-assisted thoracoscopic transdiaphragmatic liver resection in patients with a malignant tumor of the liver. Methods: Five female patients underwent video-assisted thoracoscopic transdiaphragmatic partial hepatectomy. The tumors were located at segment VIII in 4 patients and segment VII in 1. Three patients were preoparatively diagnosed with hepatocellular carcinoma, and two were metastatic tumor of the colorectal cancer. Underlying cirrhosis was staged as Child-Pugh B in 2 cases and Child-Pugh A in 1. Thoracoscopic transdiaphragmatic partial hepatic resection was chosen due to the tumor’s location and impaired liver function. The patient was placed in an oblique position with her left side on the table. The ports were placed around the tumor at three levels, the ninth (3cm mini-thoracotomy), the seventh (two ports, 5mm and 12mm), and the fifth (12mm) intercostals spaces. Using thoracoscopic ultrasonography, the portion of the diaphragm located just above the tumor was cut and opened using electric cautery. The partial liver resection was performed using coagulating shears and electric cautery. Results: No conversion to laparotomy occurred. The median blood loss was 200 g (20-500g), and median operating time was 220 min (135-347 min). There were no perioperative deaths, and no patients underwent reoperation. Conclusions: Thoracoscopic hepatic resection can be safely performed in patients with subdiaphragmatic tumors, especially with cirrhosis or previous upper abdominal surgery.
A phase III clinical trial of intra-arterial yttrium-90 glass microspheres in the treatment of patients with unresectable hepatocellular carcinoma.
Authors: Karpf Maria Angela 
Published: February 2017

477 Background: Primary liver cancer is the fifth most commonly diagnosed cancer in men and eight most common in women. Currently, sorafenib is SOC treatment for pts with advanced hepatocellular carcinoma (HCC); however, it is associated with only modest improvement in median survival compared with best supportive care. Sorafenib is associated with significant toxicity. Yttrium 90 glass microspheres (TheraSphere; 90Y) have an HDE in the US for use in radiation treatment or as a neoadjuvant to surgery or transplantation in pts with unresectable HCC who can have placement of appropriately positioned hepatic arterial catheters. The purpose of this study is to evaluate treatment with 90Y in HCC pts who will then receive SOC sorafenib and to compare survival outcomes with those of pts receiving only sorafenib. The primary objective is to evaluate 90Y in pts with unresectable HCC where SOC sorafenib is planned. Methods: This Phase 3, open-label, multi-center, randomized study will evaluate 90Y treatment in ~390 pts with unresectable HCC. Eligible pts (where SOC sorafenib therapy is already planned) will be randomized 1:1 to control and treatment. Control patients will receive SOC sorafenib according to label. The treatment group will receive 90Y prior to SOC sorafenib. Primary outcome is overall survival from time of randomization. Secondary endpoints include time to progression/untreatable progression/symptomatic progression, tumor response, quality of life, and adverse events. Sorafenib pts will have study visits every 8 wks for as long as the patient remains in study. Pts randomized to 90Y will have pre-treatment evaluations and treatment to the first lobe during wks 3-4; patients with bilobar disease will have pre-treatment evaluations and treatment to the second lobe during wks 5-8. After 90Y treatment, study visits will occur every 8 wks as long as the pts remain in study. Follow-up visits will occur every 8 wks from randomization until disease progression. Results: This study is ongoing. Conclusions: This Phase 3 study will evaluate use of 90Y in advanced HCC patients given its potential to enhance survival with less toxicity than the current SOC. Clinical trial information: NCT01556490.
Management of chemotherapy‐induced anemia (CIA) with biosimilar epoetin alfa (Binocrit) in patients with pancreatic cancer (PC): An interim analysis of an ongoing French national observational study (The OncoBOS study).
Authors: Metges Jean Philippe , Desramé Jérôme , Bourgeois Vincent , Stamerra Otilia , Mouysset Jean-Loup , Aubron-Olivier Camille , Fernet Domitille , Boschetti Gilles 
Published: February 2017

479 Background: OncoBOS is a prospective, non-interventional study describing Binocrit use in routine practice in France in patients receiving chemotherapy treatment (CT) for solid tumors, lymphoma or myeloma. This interim sub-analysis focuses on patients with PC. Methods: Patients ≥18 years with PC, CIA and eligible for treatment with Binocrit were included in this analysis. Patients characteristics, data on CIA and its management and predominant factors considered by the physician in prescribing Binocrit were recorded at baseline (BL), 3-4 weeks and 12 (± 1) weeks later. Hemoglobin (Hb) outcomes assessed included the proportion of patients achieving a Hb increase ≥1 and ≥2 g/dL, and the mean Hb change from BL. Results: 59 patients with PC (32 females (54.2%), mean age 68.3 years) from 22 sites were recruited from September 2011 to April 2014. Mean and median BL Hb levels were both 10 g/dL. The mean increase in Hb level was 1.1 g/dL after 1 month and 1.2 g/dL after 3 months (p<0.001 vs BL) of Binocrit treatment. A Hb increase ≥1 g/dL was achieved by 48.3% of patients at week 3-4 and 54.2% at week 12; a Hb increase ≥2 g/dL was achieved by 25.9% and 35.4% of patients at the same time points. Patients received a median dose of 30,000 IU Binocrit once weekly. Three of the 59 patients (5.1%) required a dose increase. Transfusion rates remained stable at 11.9% and 15.1% at week 3-4 and week 12, respectively. Oral and intravenous (IV) iron supplementation rates were low: oral iron was received by 1.7% and 0% of patients at week 3-4 and week 12, respectively; 20.3% and 13.2% of patients received IV supplementation at the same time points. Of note, iron status was assessed in only 11.9% of subjects at BL. Physicians considered quality of life (37.3%), fatigue (25.4%) and avoidance of blood transfusion (10.2%) as predominant factors in the rationale for CIA management. Over the treatment period, three treatment-related adverse reactions (non-serious) were recorded. Conclusions: This sub-analysis indicates that Binocrit, used in routine practice, is effective and well tolerated for the treatment of CIA in patients with PC.
Retrospective analysis of prognostic and predictive markers in patients with locally advanced unresectable and metastatic pancreatic adenocarcinoma treated with gemcitabine/nabpaclitaxel: Influence of the presence of stent.
Authors: Montes Ana Fernandez , Gonzalez Villarroel Paula , Valladares Ayerbes Manuel , Gómez Juan Cruz De la Cámara , Quintero Guillermo , TuÃ±as Lidia Vazquez , Fernández Mercedes Salgado , Jorge Fernández Mónica 
Published: February 2017

483 Background: Placement of a biliary stent is a standard measure for patients (pts) with pancreatic cancer. We evaluated prognostic/predictive factors that could predict the benefit of gemcitabine/nabpaclitaxel in pts with locally advanced unresectable and metastatic pancreatic adenocarcinoma and whether the presence of a biliary stent reduced the treatment efficacy Methods: We retrospectively analyzed 39 pts with locally advanced and metastatic pancreatic cancer treated with gemcitabine/nabpaclitaxel. Data included lactate dehydrogenase (LDH) level, alkaline phosphatase, neutrophil/lymphocyte ratio (NLR), performance status (PS), weight loss, presence of stent, analgesics use and CA 19.9 level. The correlation with response rate, progression-free survival (PFS) and overall survival (OS) was analyzed. Objective toxicities were assessed. Results: 30 pts (77%) had metastatic disease and 9 (23%) locally advanced pancreatic cancer. 46% had liver metastases and 41% lung metastases. Mean age of pts: 62 years (62% male). 20% had PS:0, 67% PS:1 and 13% PS:2. Stents were placed in 30% of pts, 69% had weight loss and 64% used analgesics at diagnosis. At the time of analysis 14 pts had died (25 alive). 56% had progressed, 3% were lost to follow-up and 41% had not progressed. A total of 54% disease stabilizations, 21% partial responses and 18% progressions were achieved (deaths: 7%). 43% required dose reduction. The main toxicity was hematologic (grade 1 anemia). Median PFS: 6 months (95%CI 4.4-7.6). Median OS: 15 months (95%CI 10.4-19.6). There was a statistically significant relationship between LDH level, NLR and PS and OS: LDH level higher than 363 increased the risk of death, NLR above 3.1 increased 1.8 times the risk of death and mean OS of pts with ECOG:0,1 was greater than that of pts with ECOG:2. No relationship between the presence of stent and PFS or OS was found, as well as with any of the other variables. Conclusions: The presence of stent did not reduce the efficacy of gemcitabine/nabpaclitaxel. Univariate analysis showed PS as a prognostic factor while multivariate showed LDH and NLR.
Histological evaluation of tumor response in metastatic lymph node after preoperative chemotherapy for gastric cancer.
Authors: Honda Shinsaku , Miki Yuichiro , Tanizawa Yutaka , Takagi Wataru , Hirata Fumiko , Omori Hayato , Tatsubayashi Taichi , Makuuchi Rie , Tokunaga Masanori , Bando Etsuro , Kawamura Taiichi , Nakajima Takashi , Terashima Masanori 
Published: February 2017

51 Background: Preoperative chemotherapy is thought to be an option for treatment of advanced gastric cancer. However, optimal predictive marker for survival of preoperative chemotherapy had not yet been established. Histological response is thought to be a good candidate of predictive marker, however, it had been determined only in primary tumor, not in the metastatic lymph node. The aim of this study is to evaluate the role of histological response in metastatic lymph node on the survival in patients received preoperative chemotherapy for advanced gastric cancer. Methods: A total of 38 patients who underwent curative resection after preoperative chemotherapy from were included. For histological evaluation in lymph node, we determined it as positive if remaining viable tumor cells are less than 30% of the tumor area at one or more of the resected metastatic lymph nodes. We also evaluated histological response in primary tumor according to the Japanese Gastric Cancer Classification. Results: 21 patients received preoperative chemotherapy as planned neo-adjuvant chemotherapy and remaining 17 received chemotherapy as palliative intent and then converted to surgery. Pathological TNM stage was 0 in 2, I in 5, II in 13, III in 11, and IV in 7, respectively. In lymph node, histological response was able to evaluate in 31 of 38 patients. Among them, positive response was observed in 15 patients. Histological tumor response in primary tumor was grade 0 in 2, grade 1a in 10, grade 1b in 7, grade 2 in 10, and grade 3 in 2. The 3-year relapse-free survival (RFS) rate was significantly better in patients with positive histological response in lymph node (71 %) than in those without response (21 %) (p = 0.003). Similarly, 3-year RFS rate was significantly better in patients with histological response in primary tumor (grade 2, 3) (73 %) than in those without response (grade 0, 1a, 1b) (30 %) (p=0.007). Three-year RFS in patients who demonstrate histological response both in primary tumor and lymph node was as high as 89 %. Conclusions: Histological responses in lymph nodes, as well as primary tumor, appear to be a useful predictive marker for survival in patients underwent curative resection after preoperative chemotherapy.
Expanded KRAS and NRAS assays increase detection of mutations that predict for resistance to therapy in colorectal cancer patients.
Authors: Larson Garrett , Israyelyan Anna , Lenz Heinz-Josef , Astrow Stephanie H. 
Published: February 2017

519 Background: The selection of targeted therapies is guided by the analysis of somatic mutations. The identification of RAS activating mutations can be used to examine tyrosine kinase inhibitor therapeutic eligibility and prognosis. Beyond known mutations in RAS exon 2 (codons 12 and 13), the identification of additional mutations in RAS exons 3 and 4 (codons 61, 117 and 146) also predict for resistance to EGFR therapy in colorectal cancer (CRC). Meta-analysis supports screening for these additional mutations in any screening strategy prior to administration of EGFR mAb therapy in metastatic CRC patients (Sorich, MJ, et al., Ann Oncol, Aug 12, 2014). Methods: We expanded our existing allele-specific KRAS and sequencing-based NRAS assays to include codons 61, 117, and 146 and analytically validated these assays to CAP/CLIA standards. DNA, from microdissected colon tumor tissue that was wild-type for RAS exon 2, was tested for exon 3 and 4 mutations and included over 15 additional mutations. Results: Forty-two (9.1%) samples were identified as bearing either an exon 3 or 4 KRAS mutation amongst 461 colon cancer specimens. Exon 4 codon 146 mutations were more prevalent than three of the commonly screened exon 2 mutations: G12A, G12R, and G12S. Five (1.8%) of samples were identified as carrying exon 3 or 4 NRAS mutations amongst 272 colon cancer specimens. This included a single codon 146 mutation in exon 4. As is seen with exon 2, RAS mutations at exons 3 and 4 were mutually exclusive of activating BRAF mutations with ~10% of patients harboring V600E. The collection of additional data studying KRAS and NRAS mutation status is currently ongoing. Conclusions: The KRAS expanded coverage contributed an additional 5.5% to overall burden of specimens bearing mutations. The NRAS expanded coverage contributed an additional 1.8% to the mutational burden. These analyses in clinical cohorts support the observations made in a trial population (Douillard JV, et al. NEJM 369:1023-34, 2013). The expanded RAS coverage identifies additional patients unlikely to respond to EGFR-targeted therapies that would otherwise have been assessed as “no mutation detected” in using assays restricted to RAS exon 2.
Baseline blood neutrophil-lymphocyte ratio to predict treatment response in gastric cancer.
Authors: Diaz Romero M 
Published: February 2017

52 Background: Several studies have shown that the neutrophil to lymphocyte ratio (NLR) in peripheral blood is a prognostic factor of various cancers. Some biomarkers have been associated with response and prognosis in gastric cancer (GC)identify depends specimens on biopsies and limits their use in clinical practice.Pheripheral blood tests at the time of diagnosis can reflect evolution within the tumor. We evaluated whether the NLR would predict response in patients with GC with treatment neoadyuvant or palliative. Methods: We retrospectively analyzed 190 patients with GC (2011-2013) in National Cancer Institute Mexico. 73 patients were treated with chemotherapy neoadjuvant, 30 with chemoradiotherapy neoadjuvant and 117 patients palliative chemotherapy. NLR were calculated from complete blood counts in laboratory test at diagnosis, cutt of values for the NLR were > 2.5 and < 2.5 using median values reported in previous studies. Results: Characteristics of Patients: male 107, female 83, mean age 54 (20-81).The median number of cycles of chemotherapy before of assess response by tomography was 4. The response rate was partial 20.5%, stable disease 36.3% and progression 43.2%.The median NLR :2.9 (1.1-15.2).84 patients were detected with NLR < 2.5 and 106 patients with NLR greater 2.5. Low NLR group patients had a better disease control (partial response and stable disease) in 68 % vs. 47.1% than high NLR( p = 0.028). Progression of disease was reported in 32 %( n=27) with low NLR and 52.9 %( n=56) of group high NLR (P=0.002). Patients with neoadjuvant treatment 50 underwent surgery 30 with NLR ratio lesser 2.5 and 20 high.There are more advanced disease in patients greater 2.5 NLR than < 2.5 80 vs 56 (p=0.036). Response pathological complete after surgery in 2 patients with a lower value and 1 patient with 2.5. Overall survival in low NLR is longer than in group patients NLR >2.5, 11.3 vs. 9.1 months (p=0.49). Conclusions: These data give evidence that baseline NLR could be predictive marker of response and prognosis in patients with GC undergoing treatment. Limitations to our analysis are a small number of patients, short follow-up and will need to be stratified according to patient characteristics and treatment.