bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodality management of borderline resectable pancreatic neuroendocrine tumors: Sentinel report of a single-institutional experience.
Authors: Ambe Chenwi , Nguyen Phuong , Centeno Barbara , Choi Junsung , Strosberg Jonathan R. , Kvols Larry K. , Hodul Pamela Joy , Hoffe Sarah E. , Malafa Mokenge Peter 
Published: February 2017

418 Background: Pancreatic neuroendocrine tumors (PNET) constitute about 3% of pancreatic neoplasms. In borderline resectable disease, there is a lack of data to support an optimal neoadjuvant approach for curative outcomes. We describe our institutional experience with a multimodality approach. Methods: We identified all patients with borderline resectable PNET, using NCCN criteria for adenocarcinoma of the pancreas, who received neoadjuvant therapy at our institution between 2000 and 2013. The reason for borderline status was noted. Neoadjuvant regimen, radiographic response, pathologic response, surgical margins, nodal harvest, number of positive nodes, and recurrence were all documented. Results: A total of 112 patients had undergone pancreatic resections for neuroendocrine tumors during the study period. Six patients had borderline resectable disease. The mean age was 55 years (24-70). They all received at least 1 cycle of Temodar and Xeloda. Three of the six patients also received concurrent 5-FU and radiation. There was radiographic evidence of treatment response in all patients. Five of six patients (83 %) had negative margin (R0) resection. Low volume miliary metastatic disease in the liver was detected in 1 patient at the time of surgery. The median number of lymph nodes harvested was 12. Half of the patients had node positive disease. On pathologic review, 4 patients had histologic evidence of a moderate response. All patients are alive and 5/6 are free of disease. Range of follow up is 3.0-4.32 years. The patient with metastatic disease has had no progression and is the only one who is currently receiving any form of treatment. Conclusions: Neoadjuvant Temodar and Xeloda ± radiation with 5-FU sensitization can lead to R0 resection with durable response in patients with borderline resectable PNET. To our knowledge, this is the first report of the use of multimodality therapy (neoadjuvant chemotherapy ± chemoradiation and surgery) in the treatment of borderline resectable PNET.
A randomized phase II trial of antithrombin (AT) products in patients with disseminated intravascular coagulation (DIC) associated with sepsis in advanced pancreatic and biliary cancer.
Authors: Tamura Takeshi , Ioka Tatsuya , Sueyoshi Hironari , Takada Ryoji , Fukutake Nobuyasu , Ashida Reiko , Ohkawa Kazuyoshi , Katayama Kazuhiro 
Published: February 2017

423 Background: A randomized phase 2 trial was conducted in order to investigate the most effective administration method of antithrombin (AT) products in patients with disseminated intravascular coagulation (DIC) associated with sepsis during treatment for advanced pancreatic and biliary cancer (aPBC). Methods: Diagnoses of DIC were made according to the criteria of acute DIC of the Japan Association of acute Medicine. We examined 42 patients who were diagnosed with septic DIC and showed a level of AT lower than 70% during treatment for aPBC. The patients were evenly divided into two groups: Group A (21 patients) received continuous infusions of AT products 1500 IU per day for three days, and the group B (21 patients) received intermittent infusions of AT products 500 IU×3 per day for three days. Changes in the coagulation parameters, inflammatory markers, SIRS positive scores, and DIC scores that occurred during treatment were compared between the two groups. Furthermore, the survival outcomes of the patients were evaluated using the Kaplan-Meier method. Results: Before treatment, there were no significant differences between the two groups with respect to their backgrounds. During treatment, statistically significant differences were seen in the platelet counts, D-dimer test results, Fibrinogen levels, and CRP levels between the two groups. However, no differences were observed between the two groups regarding the changes of AT activity levels, SIRS positive scores, and DIC scores. No statistically significant differences were noted between the groups in regards to their survival outcomes (28 day survival rates: 85.7% versus 71.4%, p=0.283). A multivariate analysis indicated that baseline AT activity levels were the sole factor associated with the 28-day survival rates. The survival outcomes didn’t depend on the administration method of AT products. Conclusions: In this trial, we found that baseline AT activity levels were the sole factor associated with the 28-day survival rates. There was no difference in therapeutic effects between the continuous and intermittent infusions of AT products. Clinical trial information: UMIN 000015105.
Pretreatment diffusion weighted imaging for clinical outcome assessment in patients undergoing definitive chemoradiation for pancreatic adenocarcinoma.
Authors: Buchwald Zachary S , Olsen Jeffrey R. , Badiyan Shahed Nicolas , DeWees Todd A. , Hu Yanle , Fields Ryan C. , Wang-Gillam Andrea , Parikh Parag J. 
Published: February 2017

432 Background: Factors predicting patterns of failure for pancreatic ductal adenocarcinoma (PDA) are not well-established. Diffusion-weighted MRI (DWI) is useful in predicting recurrence for other gastrointestinal malignancies. The purpose of this study was to evaluate for correlation between tumor DWI parameters and clinical outcomes following chemoradiotherapy (CRT) for pancreatic adenocarcinoma. Methods: From 2009 to 2013, 27 patients with locally advanced (n=14), borderline resectable (n=12) or resectable (n=1) PDA underwent CRT. All patients received upfront FOLFIRINOX or gemcitabine-based chemotherapy prior to CRT, and gemcitabine (median weekly dose 800 mg/m2) concurrent with radiotherapy. DWI was obtained during radiotherapy treatment planning, and apparent diffusion coefficient (ADC) maps were generated to allow determination of median tumor ADC. Tumor-directed CRT was administered with respiratory gated intensity modulated radiation therapy, 55Gy in 25 fractions without elective nodal coverage. Patients were followed by imaging every 2-3 months. Log rank test was used to estimate an optimal ADC cut-point of 1.4*10-3mm2/sec based on distant metastasis free survival (DMFS) and overall survival (OS). Analysis of local recurrence was not performed due to limited events. The log-rank test was used to evaluate differences in outcome between groups based on ADC classification. Results: The median time to last follow-up from completion of CRT was 9.7 months for all patients and 11 months among living patients. 5 patients underwent resection following CRT. The 1-year DMFS for patients with median ADC<1.4*10-3mm2/sec was 79.5 percent, compared to 47.6 percent for those with median ADC >1.4. The 1-year OS for patients with median ADC<1.4 was 100 percent, compared to 46.3 percent for those with median ADC >1.4. Both DMFS (p=.041) and OS (p=.003) were significantly improved on log-rank test for ADC<1.4 compared to ADC>1.4. Conclusions: A correlation was observed between DWI parameters and clinical outcomes for PDA. Further prospective study should be explored to validate DWI as a prognostic imaging biomarker.
Pretreatment albumin may help select patients for intrahepatic Y-90 microsphere transarterial radioembolization (TARE) for malignancies of the liver.
Authors: Orwat Kelly Elizabeth , Cooper Samuel Lewis , Ashenafi Michael , Anderson M. Bret , Guimaraes Marcelo , Marshall David T. 
Published: February 2017

453 Background: Systemic therapies for unresectable liver malignancies may provide a survival benefit, but eventually prove intolerable or ineffective. TARE provides an additional liver-directed treatment option to improve local control for these patients, but there is limited data on patient factors associated with survival. Methods: All patients that received TARE at the Medical University of South Carolina from March 2006 through May of 2014 were included in this analysis of overall survival (OS) and toxicity. Kaplan-Meier estimates of OS from date of first procedure are reported. Potential prognostic factors for OS were evaluated using log rank tests and Cox proportional hazards models. Results: In 114 patients that received TARE at our institution, median follow-up was 6.4 months [range 0-86], with the following tumor histology: colorectal (CR) n=55, hepatocellular (HC) n=20, cholangiocarcinoma (CC) n=16, neuroendocrine (NE) n=12, breast (BR) n=6, other n=5. At least 1 line of systemic therapy prior to TARE was noted in 79% of patients. Median OS was 6.6 months and 1-year OS was 30.7%. The percentage of patients who died within 3 months of TARE were 46.2% for patients with albumin < 3 but only 20.3% for patients with albumin ≥ 3. Grade ≥ 2 toxicity was observed in 22 patients (19.3%) including 9 (7.9%) with Grade 3 and 1 (0.9%) with Grade 4 toxicity. A single patient with a pre-existing pulmonary arteriovenous malformation experienced Grade 3 pneumonitis that resolved with steroids. No deaths were attributed to radiation-induced liver disease. Conclusions: TARE is a relatively safe and effective treatment for unresectable intrahepatic malignancies. Patients with NE or BR histology as well as those with better hepatic synthetic function were associated with significantly better survival. Our data suggest that patients with albumin below 3 may not benefit from TARE. [Table: see text]
Incidence of brain metastasis in esophageal cancer.
Authors: McCann Brendan , Bhatti Kiran , MacLaren Vivienne 
Published: February 2017

46 Background: Brain metastasis in oesophageal cancer is a rare but often fatal complication. In previous studies the incidence has ranged from 1.4% - 13% with the largest studies from China and Japan that have been retrospectively based over fifteen to twenty years. (Ogawa K, Toita T, Sueyama H. Brain metastases from esophageal carcinoma: natural history, prognostic factors, and outcome. Cancer. 2002 Feb 1;94(3):759-64.) With improving diagnostic techniques and differing histology of oesophageal cancer from Eastern countries we undertook a study to determine the incidence of brain metastases in oesophageal cancers in the West of Scotland. Methods: Data from all the new patients diagnosed with oesophageal cancer was obtained with permission from the Regional Managed Clinical Network from the years 2011 and 2012 yielding a total of 701 patients. The individual clinical records were examined to ascertain if the patient developed brain metastases on CT/MRI scan, their tumour type and management. Results: Of the 701 patients diagnosed with oesophageal cancer, 19 developed brain metastasis demonstrating an incidence of 2.7%. 12 of these patients primary diagnosis was adenocarcinoma. The others were small cell (3), neuroendocrine (2), squamous (1) and no histology (1). At the time of writing 17 out of 19 patients had died from their oesophageal cancer. The 2 surviving patients had a single brain metastasis that was resected and treated with adjuvant radiotherapy. 6 other patients had whole brain radiotherapy, 1 patient had partial brain radiotherapy and 10 were managed with best supportive care. Mean survival from diagnosis of brain metastasis for best supportive care was 26 +/- 14 days versus mean survival for radiotherapy treatment from 100+/- 57 days (p = 0.003) demonstrating a difference between the groups. Conclusions: The incidence of brain metastasis in oesophageal cancer in the West of Scotland was 2.7% with the prognosis generally poor unless resected.
The use of an interposed graft during portal vein and/or superior mesenteric vein reconstruction in pancreatic resection for pancreatic cancer.
Authors: Yamaue Hiroki , Hirono Seiko , Kawai Manabu , Okada Ken-Ichi , Miyazawa Motoki , Shimizu Atsushi , Kitahata Yuji , Ueno Masaki 
Published: February 2017

482 Background: Combined portal vein and/or superior mesenteric vein (PV/SMV) resection with pancreatectomy sometimes leads to prolonged survival for patients with periampullary tumors. In this study, we evaluated outcomes of patients with PV/SMV reconstruction, and we considered indications for the use of a graft during this procedure. Methods: We performed PV/SMV resection with pancreatectomy in 128 patients with periampullary tumors, including 14 using grafts. Short and long-term outcomes associated with PV/SMV reconstruction and harvesting venous grafts and reconstructed PV/SMV patency during follow-up were assessed. Results: Of the 128 patients with periampullary tumors, 5 underwent total pancreatectomy, 99 pancreaticoduodenectomy, and 24 distal pancreatectomy. In the 14 patients who underwent PV/SMV reconstruction with grafts, the grafts were harvested from external iliac vein in 10 patients and internal jugular vein in the other 4. Five patients (3.9%) had intraoperative or postoperative acute thrombus or stenosis of reconstructed PV/SMV after direct end-to-end anastomosis. However, PV/SMV patency was excellent after reconstruction using grafts. Among 228 patients with common pancreatic cancer, there were no significant differences in overall survival (OS) between the patients with PV/SMV resection (n=99) and without PV/SMV resection (n=206) (P=0.354), although the lymph node metastasis rates in the patients with PV/SMV resection were higher than those without PV/SMV resection (78.8 vs. 64.6%, P=0.012). Furthermore, the tumor size in the patients with the use of a graft was larger than that without a graft (Mean size; 40.5 vs. 29.3 mm, P=0.047), and the R0 rates and OS were not different between the patients with and without a graft (R0 rates; 50 vs. 73%, P=0.129 and OS; 23.4 vs. 16.6 months, P=0.323). Conclusions: Depending on the length and/or position of the removed PV/SMV segment, an interposed graft may be required for reconstruction in some patients.
Second primary cancers in young adult colorectal cancer survivors.
Authors: Shameem Raji , Hamid Muhammad Saad , Godwin James Luke , Sonpal Niket , Sullivan Kevin M. 
Published: February 2017

516 Background: Second primary cancers are a major concern for young adult colorectal cancer (CRC) survivors. The impact of treatment with radiation on the risk for second solid and hematological malignancies, as well as the typical latency period before development of a second cancer, requires elucidation. Methods: The Surveillance Epidemiology and End Results (SEER) database was used to detect CRC cases in young adults (aged 20-40 years) diagnosed up to 12/31/2011. The Standardized Incidence Ratio (SIR) was calculated as the ratio of observed to expected cases of second primary malignancy based on incidence data in the general United States population. The latency exclusion period from the date of diagnosis was 5 years. We investigated the possible effect of radiation therapy on risk for a second cancer, and established the typical latency period after initial diagnosis (5-10 years and >10 years). Results: A total of 9,537 cases of CRC in young adults were available for analysis. Radiation was administered in 1,823 (19.1%) patients. Second primary cancers occurred in 798 cases, 754 (94.5%) solid tumors and 44 (5.5%) hematological malignancies respectively. In the latency period 5-10 years after initial diagnosis, “All Solid Tumors” (SIR: 1.85, p<0.05) and female genital tumors (SIR: 3.52, p<0.05) were increased. In the latency period >10 years after initial diagnosis, an increased risk of developing pancreatic cancer (SIR: 1.90, p<0.05) and female genital tumors (SIR: 1.77, p<0.05) was observed. In patients who received radiation the only significantly increased risk was for “All Solid Tumors” (SIR: 1.42, p<0.05). No significant increase in second hematological malignancies was observed in the entire cohort, including cases that received radiation. Conclusions: An increased risk of second primary female genital tumors was seen in both the 5-10 years and >10 years latency periods. Pancreatic cancer risk was increased specifically in the >10 years latency period. Radiation treatment did not pose an increased risk for any specific second primary cancers. Interestingly, young adult CRC survivors did not have an increased risk for hematological malignancies compared to the general population.
Circulating tumor DNA (ctDNA) in nonmetastatic colorectal cancer (CRC): Potential role as a screening tool.
Authors: Tie Jeanne , Wang Yuxuan , Kinde Isaac , Steel Malcolm , Elsaleh Hany , Singh Madhu Sudan , Turner Natalie Heather , Tran Ben , Strausberg Robert , Diaz Luis A. , Papadopoulos Nickolas , Kinzler Kenneth W. , Vogelstein Bert , Gibbs Peter 
Published: February 2017

518 Background: CRC screening significantly reduces cancer incidence and mortality. Participation rates in screening, both stool based and endoscopic, are often low. The value and safety of endoscopic screening in older individuals is also uncertain. Preliminary data indicate ctDNA can be detected in a high proportion of patients with early stage CRC, suggesting promise as a screening test that should have broad community acceptance. Methods: Plasma samples were collected at diagnosis from 100 patients (pts) with newly diagnosed CRC. Surgical, clinicopathologic and outcome data were prospectively captured. All samples were sent to Johns Hopkins Kimmel Cancer Center, where tumors were sequenced using a panel of 15 genes frequently mutated in CRC to identify candidate mutations for ctDNA analysis. For each pt, one tumor mutation was selected to assess for ctDNA in plasma samples using the Safe-SeqS digital genomic assay. Results: Preliminary data is available on 68 pts. Median follow-up is 15.2 months. Candidate mutations for ctDNA analysis were identified in all cases, with a matching mutation detectable in the plasma cell-free DNA in 41 pts (60%). Median mutant allele fraction was 0.24% (range 0.11% - 8.39%). Tumor stage did not appear to have a major impact on the detection rate of ctDNA (Table), and ctDNA detection was independent of CEA levels. Five pts have recurred, all of whom had detectable ctDNA at diagnosis, whereas CEA was elevated in only 1 of these cases. Conclusions: Preliminary data suggests ctDNA is detectable at diagnosis in the majority of pts with non-metastatic CRC. The potential for ctDNA as a CRC screening tool, and as a prognostic marker for patients with early stage cancer, should be further explored. [Table: see text]
Observational cohort study of first-line bevacizumab combined with chemotherapy in metastatic colorectal cancer (HGCSG0802): Comparison of infusional FU/oxaliplatin(OX)+BV and oral FU/OX+BV.
Authors: Hatanaka Kazuteru , Yuki Satoshi , Nakatsumi Hiroshi , Fukushima Hiraku , Naruse Hirohito , Kato Takashi , Meguro Takashi , Nakamura Michio , Iwanaga Ichiro , Uebayashi Minoru , Tateyama Miki , Eto Kazunori , Kudo Mineo , Kato Sosuke , Okuda Hiroyuki , Sogabe Susumu , Miyashita Kencho , Sakata Yuh , Komatsu Yoshito 
Published: February 2017

527 Background: A few reports have shown no difference between the efficacy of infusional FU and that of oral FU (Capecitabine/S-1) for colorectal cancer, and some studies have reported the non-inferiority between infusional FU/Oxaliplatin (OX) and oral FU/OX for metastatic colorectal cancer (mCRC). We performed a sub-group comparison between infusional FU/OX (mFOLFOX6 + BV: iFU) and oral FU/OX (CapeOX/SOX + BV: oFU) from the HGCSG0802 observational cohort study with investigated Japanese patients (pts) treated with first line BV for mCRC. Methods: The objective of HGCSG0802 was to evaluate progression-free survival (PFS), overall survival (OS), time to treatment-failure (TTF), response rate (RR), safety and so on. The key eligibility criteria of HGCSG0802 were with evaluable lesions, older than 20 years, ECOG PS 0-2, and this analysis used the cohort treated with OX-based regimens.In this analysis, pts characteristics, RR and safety were compared using Fisher’s exact test. PFS and TTF were compared using log-rank test. Results: Of 108 pts (the full analysis set), 95 pts were evaluable for treated with OX-based regimens. Forty-eight pts (50.5%) were treated with iFU and 47 pts (49.5%) were treated with oFU (CapeOX + BV 42 pts/SOX + BV 5 pts). The pts characteristics between those were generally balanced except for PS 0-1 (72.9% in iFU/93.6% in oFU; p=0.012) and synchronous liver metastases (mets) (93.8% in iFU/78.8% in oFU; p=0.040). Adverse events ≥grade 3 were balanced except for leucopenia (25.0% in iFU versus 2.1% in oFU; p=0.002) and neutropenia (43.5% in iFU and 10.9% in oFU; p=0.001). Hand-foot skin reaction was not different between two cohorts. RR was 62.5% in iFU versus 71.1% in oFU (p=0.835). The median PFS was 8.3 months in iFU versus 8.2 months in oFU (p=0.835). Conclusions: The HGCSG0802 could be a database to investigate first line BV for mCRC in clinical practice. As a result of this analysis, in Japanese daily practice, efficacy was no significant difference between infusional FU/OX and oral FU/OX, and the profiles of adverse events varied from each regimens.
Incidence of hyponatremia in a cohort of patients with colorectal cancer.
Authors: Castillo Jorge J. , Glezerman Ilya , Boklage Susan , Chiodo Joseph , Schulman Kathy L. 
Published: February 2017

545 Background: Hyponatremia (HN), a common electrolyte disturbance in hospitalized patients, is a prognostic factor in some cancers. The incidence of HN in patients diagnosed with colorectal cancer (CRC) is unknown and is investigated here. Methods: This retrospective cohort analysis combined electronic medical record and tumor registry data from an integrated delivery network. Patients included were adults diagnosed with incident invasive CRC between 2005 and 2011 with ≥1 administration of radiation or chemotherapy within 6 months of diagnosis who met continuous clinical activity criteria. Exclusions included unknown index cancer stage or ≥1 post-index hypovolemic HN episode. Patients were followed until study end, death, clinical trial entry, new primary cancer onset, or end of continuous clinical activity. HN incidence (serum sodium ≤135 mEq/L) was measured per 1,000 person years (PY) of observation (95% confidence intervals [CI]) and classified as mild (131–135), moderate (125–130) or severe (<125) based on the lowest observed value. Results: In all, 132 CRC patients were included (52% male; mean [SD] age 64±13.1 years, 99% Caucasian). Mean (SD) follow-up was 3±2.6 years. Thirty-six percent of patients had metastatic disease at diagnosis and 80% received chemotherapy, 39% radiation therapy and 83% surgical resection. Patients with HN post-CRC diagnosis had significantly greater incidence of metastatic disease during follow-up (p=0.033) and exposure to anti-metabolites (p=0.023) or platinum based agents (p=0.017). Episodes of HN (n=262) occurred in 81 patients (61%) at a rate of 598 per 1,000 PY (95% CI, 523–680). Mean (SD) episodes per patient were 1.8±2.6. Overall, 84% of episodes were mild, 14% moderate and 2% severe; 52% were classified as syndrome of inappropriate antidiuretic hormone secretion. Mean (SD) time to first hyponatremia episode was 139±296 days, with a median duration of 12 days; 84% of patients had a first episode within the first 6 months. Conclusions: The incidence of HN after diagnosis with CRC was about 61% and episodes occurred primarily within 6 months of diagnosis. Based on these results, along with emergent evidence from other studies, clinicians should anticipate HN in newly-diagnosed CRC patients.