bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microwave ablation for hepatic malignancies: A multi-institutional analysis.
Authors: Groeschl Ryan Thomas , Pilgrim Charles Henry Caldow , Hanna Erin Marie , Simo Kerri A , Swan Ryan Z , Sindram David , Martinie John B , Iannitti David A , Bloomston Mark , Schmidt Carl Richard , Khabiri Homan , Shirley Lawrence Andrew , Martin Robert C. G. , Christians Kathleen K. , Rilling William S , Gamblin T. Clark 
Published: February 2017

218 Background: Although many hepatobiliary centers have moved from radiofrequency ablation to microwave ablation (MWA), the factors that influence local control with MWA are not well described. We hypothesized that tumor size, number of tumors, and tumor histology significantly affected MWA success and recurrence-free survival (RFS). Methods: Consecutive patients with hepatic malignancy treated by MWA were included from 4 high-volume institutions (2003-2011), and grouped by histology: hepatocellular cancer (HCC), colorectal metastases (CM), neuroendocrine metastases (NM), and other cancers. Independent significance of variables was established with logistic regression and Cox proportional hazards models. Results: Four-hundred seventy three ablation procedures were performed (139 HCC, 198 CM, 61 NM, and 75 other) for a total of 875 tumors. Median follow-up was 18 months. Complete ablation was confirmed for 839 of 865 tumors (97.0%) on follow-up cross-sectional imaging (Table). NM had greater odds of an incomplete ablation compared to other histologies (odds ratio: 3.07, 95% confidence interval [CI]: 1.08-8.67, p=0.035), however this was not significant in adjusted models. The local recurrence rate was 6.1% overall, and was highest for HCC tumors (10.3%, p=0.051). RFS did not vary significantly between histologies. In adjusted models, tumor size ≥3cm was the only variable predicting poorer RFS (hazard ratio: 1.60, 95% CI: 1.02-2.50, p=0.039). Independent predictors of poorer OS included age, number of tumors ablated, and tumor size ≥3cm. Conclusions: In this large dataset, patients with ≥3cm tumors showed a propensity for early recurrence, regardless of histology. Higher rates of local recurrence were noted in HCC patients, which may reflect underlying liver disease. Accounting for recurrence at any site, however, there were no significant differences in RFS between tumor histologies. [Table: see text]
Phase I trial of chemoradiation with capecitabine and vorinostat in pancreatic cancer.
Authors: Chan Emily , Arlinghaus Lori R. , Cardin Dana Backlund , Goff Laura Williams , Yankeelov Thomas E. , Berlin Jordan , McClanahan Pamela , Holloway Melanie , Parikh Alexander A. , Abramson Richard G. , Merchant Nipun B. , Hiebert Scott , Chakravarthy Anuradha Bapsi 
Published: February 2017

225 Background: Histone deacetylase inhibitors (HDACi) and fluoropyrimidines are synergistic and are radiation (R) sensitizers. The combination of the fluoropyrimidine capecitabine ( C) and the HDACi vorinostat (V) with R was evaluated in the treatment (tx) of non-metastatic pancreatic cancer (NMPC). Methods: Patients (Pts) with NMPC were treated with C + V + R. C dose was 1000 mg q12 Monday (M) - Friday (F) on the days of R. R was given via 3D conformal therapy to a total dose of 3000 cGy in 10 fractions over 2 weeks (wk). V dose was given daily M-F x 4 wk. V doses evaluated were: 100, 200, 300, and 400 mg. Resectability assessment occurred within 6 wk after completion of tx. Diffusion weighted- MRIs (DW-MRIs) were obtained pre tx and one wk after tx initiation to assess tumor cellularity. Peripheral blood mononuclear cells (PBMCs) were collected pre tx, during tx, and after completion to assess whole cell HDAC activity. Unresectable pts could opt for continuation of C and V (CCV) at systemic doses (C 1000 mg q12 x 14 days and V 300 mg QD x 14 days of every 21 day cycle) or come off study. Results: 18 pts were enrolled and evaluable. Disease statuses pre-tx were: resectable (n=1), borderline resectable (n=9), and unresectable (n=8). One DLT occurred at dose levels 1, 3, and 4, 2 GI toxicities and one thrombocytopenia. Most common adverse events were lymphopenia, GI toxicity, and fatigue. On MRI, the apparent diffusion coefficient (ADC) increased in most, but not all, tumors after one wk of tx but did not correlate to change in tumor size at completion. PBMC histone acetylation increased in some pts. Eight pts (Pre-tx status: 1 resectable and 7 borderline resectable) underwent exploration with 4 undergoing tumor resection. No unresectable pt converted to resectable. Four of ten potential pts opted for CCV after being deemed unresectable, 2 with stable disease for 6 cycles. Conclusions: C + V + R is feasible with no unexpected toxicity. HDAC inhibition and ADC decrease on DWI-MRI was seen. Accrual to the final cohort (V 400 mg) is ongoing. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) from general research support provided by Merck & Co., Inc. Study was also supported by the Vanderbilt-Ingram Center Support Grant P30CA68485. Clinical trial information: NCT00983268.
Comparison of investigator-delineated GTV in chemoradiotherapy (CRT) for locally advanced nonmetastatic pancreatic cancer (LANPC): Analysis of the pretrial test case for the SCALOP trial.
Authors: Mukherjee Somnath , Halle Charlotte , Spezi Emiliano , Joseph George , Branagan Jennifer Mary Rose , Hurt Chris , Falk Stephen , Nixon Lisette , Abrams Ross A. , Staffurth John 
Published: February 2017

230 Background: SCALOP, a randomized, multicenter, phase II trial, tested efficacy/toxicity of gemcitabine (Gem) versus capecitabine (Cap) based CRT following 4 cycles of induction chemotherapy. 114 patients from 28 centers were registered and 75 patients had CRT. The RT Quality Assurance included a test case. GTVs outlined by investigators were evaluated by the chief investigator (CI). We report analysis of the test case. Methods: The test case was LANPC of head of pancreas. The gold standard GTV (gsGTV) was outlined by the CI and trial radiologist. Protocol specified margins (GTV + 2cm sup-inf, 1.5 cm radial) were applied to generate the gold standard PTV (gsPTV). CT-DICOM dataset of the planning scan was sent to participating centers for tumor volume delineation by investigators and individualized feedback was provided by CI. CERR software was used to compare the investigator volumes (iGTV and iPTV) against the gold standard. Results: Volumes from 25 investigators were analyzed. The results are summarized below (Table). Slice-by-slice conformity indices and qualitative review showed that most variation occurred at the superior and inferior extremes of the tumor and a peri-tumoral node was frequently missed by investigators. Conclusions: SCALOP is the first trial in LANPC to test investigator-delineated volumes using conformity indices, and has demonstrated considerable variation in iGTVs. Trial workshops and real-time central review of tumor outlines are proposed. [Table: see text]
Duodenal sparing stereotactic body radiation therapy for the treatment of locally advanced pancreatic cancer.
Authors: Ghaly Maged , Montchal Elaine , Cao Yijan , Marrero Mihala , Vijeh Lili , Xanthopoulos Eric , Vinciguerra Vincent , Kaushik Neeraj , Sullivan James , Bloom Beatrice , Knisely Jonathan 
Published: February 2017

254 Background: The proximity of the pancreas to bowel presents a unique challenge for pancreatic cancer SBRT. This study explores the safety and effectiveness of a novel approach optimizing pancreatic tumor coverage and duodenal sparing. Methods: Eighteen patients with locally advanced pancreatic cancer (15 head/3 body) were treated with initial chemotherapy (Gemcitabine or 5-FU/Cisplatin) for 2- 6 months. All underwent endoscopic US-guided fiducial placement in and around the tumor and had a 4D treatment planning CT scan with oral contrast. This CT was used in conjunction with EUS findings, PET, and biphasic CT scans to identify the GrossTumorVolume (GTV) on the expiration phases. The planning target volume (PTV) was created by expanding the GTV by 2 mm. Dose-volume histogram (DVH) endpoints were constructed, keeping V7/15/20 (stomach/duodenum volumes that receive 7 Gy/15 Gy/20 Gy) <40%,/<25%/ <15% ;the dose to 1/3 of the duodenal circumference <20Gy and duodenal point max dose <23 Gy. Additional dose constraints included liver D50<5 Gy, ipsilateral kidney D25<5 Gy, cord Dmax<10Gy. Three 10 Gy fractions, normalized to the 85% isodose were delivered to the PTV on consecutive weekdays using fiducial-based respiratory motion tracking on a dedicated 6 MV linac-integrated stereotactic delivery system . The patients were then offered systemic therapy for 6 months or until tolerance or disease progression. Follow-up occurred at 4 weeks, 12 weeks, and every 3 months. Results: All patients completed SBRT and a median of 5 total cycles of pre-and post-SBRT chemotherapy. Gross target volumes ranged from 14.2-205.7cm3 (median 39.5cm3). With a median follow-up of 10 months, 1 patient developed transient gastroparesis, 1 G 2 abdominal pain;1 G 2 hematologic toxicity. No late toxicity was observed in 15 patients with longer follow-up (median 12 month). All patients were free of local progression at the last follow-up visit (range 3-12 months). Conclusions: Linac-delivered organ-sparing SBRT with chemotherapy in locally advanced pancreatic cancer resulted in excellent local control and also was well tolerated acutely and subacutely. Longer follow-up is warranted. A phase I dose-escalation study is underway.
Outcomes with FOLFIRINOX for locally advanced pancreatic cancer.
Authors: Boone Brian A. , Steve Jennifer , Krasinskas Alyssa M. , Zureikat Amer H. , Lembersky Barry C. , Gibson Michael K. , Stoller Ronald , Zeh Herbert J. , Bahary Nathan 
Published: February 2017

256 Background: Trials examining the use of FOLFIRINOX in metastatic pancreatic ductal adenocarcinoma demonstrate significantly higher response rates compared to gemcitabine-based regimens. These high response rates may be particularly important for patients with locally advanced pancreatic ductal adenocarcinoma (LAPD), in which there is currently limited experience with FOLFIRINOX. We examined the outcomes of patients with LAPD treated with neoadjuvant FOLFIRINOX at our high volume clinic. Methods: Retrospective review of a prospectively maintained pancreatic cancer database was used to identify patients who were recommended neoadjuvant treatment with FOLFIRINOX. Clinical outcomes were reviewed. Resectability was determined using SSO criteria. Results: Between 2/2011 and 9/2012 FOLFIRINOX was recommended for 25 patients with LAPD, 13 (52%) unresectable (UR) and 12 (48%) borderline resectable (BR). Median age was 59. 4 patients (16%) either refused treatment or were lost to follow up. 21 patients (84%) were treated with a median of 4.7 cycles (Range: 2-8). 5 patients (24%) required dose reductions secondary to toxicity. 2 patients (9%) were unable to tolerate treatment and 3 patients (14%) had disease progression on treatment. Of the remaining 16 patients, 13 patients (62%) displayed a radiologic response allowing for surgical exploration, 4 (31%) of which were initially unresectable. 6 of these patients (29%) received additional chemotherapy and/or radiation therapy prior to surgery. Peritoneal metastases were discovered at surgery in 2 (8%) patients. Of the patients who were BR, 7/8 (88%) had a R0 resection. Of the 10 UR patients, 3 (33%) underwent surgical resection, with 2 (20%) R0 resections. Overall R0 resection rate was 43%. A total of 4 patients (19%) demonstrated a major pathologic response (2 complete responses and 2 near complete responses) and 8 other patients (73%) had some pathological response. Conclusions: FOLFIRINOX alone or as part of multimodality approach is a biologically active regimen in LAPD with encouraging R0 resection rates, especially in BR LAPD. Further research is needed to determine the utility of additional chemoradiotherapy with FOLFIRINOX and to identify predictors of response in UR patients.
Intravenous and intraperitoneal paclitaxel with S-1 for refractory pancreatic cancer with malignant ascites: An interim analysis.
Authors: Takahara Naminatsu , Isayama Hiroyuki , Nakai Yousuke , Sasaki Takashi , Ishigami Hironori , Yamaguchi Hironori , Kogure Hirofumi , Yamamoto Natsuyo , Sasahira Naoki , Hirano Kenji , Tada Minoru , Kitayama Joji , Watanabe Toshiaki , Koike Kazuhiko 
Published: February 2017

267 Background: Here we reported an interim analysis of feasibility and safety in the first 10 cases of 30 cases in a phase II trial of intravenous and intraperitoneal paclitaxel combined with S-1 for gemcitabine-refractory pancreatic cancer with malignant ascites. Methods: Paclitaxel was administered intravenous at 50 mg/m2 and intraperitoneal at 20 mg/m2 on days 1 and 8 every 3 weeks, and S-1 was administered at 80 mg/m2/day for 14 consecutive days, followed by 7 days rest. Results: Between April 2011 to February 2012, 10 patients were enrolled. A partial response was achieved in two (20%) and a disease control rate of 50%. The median time to progression and overall survival were 3.2 and 5.9 months, respectively. Malignant ascites was completely resolved in two (20%). Major grade 3/4 adverse events weremyelosuppression including neutropenia (50%) and catheter-related infection (10%). Conclusions: This novel combination chemotherapy was feasible and showed promising results in pancreatic cancer patients with malignant ascites. Clinical trial information: UMIN000005306.
A phase I study of hyperfractionated low-dose radiotherapy (RT) as a chemotherapy sensitizer in combination with gemcitabine (G) and erlobtinib (E) in advanced pancreatic cancer.
Authors: Konski Andre A. , Meyer Joshua E. , Philip Philip Agop , Shields Anthony Frank , Hall Michael J. , Choi Minsig , Duncan Gail , Adaire Beth , McSpadden Erin , Cohen Steven J. 
Published: February 2017

268 Background: G can sensitize pancreatic cancer (PC) to radiotherapy (RT). However, this approach requires lower doses of G and thus delays aggressive systemic treatment, which may lead to distant failure. In preclinical models, hyperfractionated low-dose RT sensitizes PC cells to G and erlotinib. We thus initiated a Phase I trial combining hyperfractionated low-dose RT combined with full dose G and a tyrosine kinase inhibitor, E, in the treatment of patients with advanced PC. Methods: Patients (pts) with locally advanced or metastatic PC confined to the abdomen and an ECOG performance status (PS) of 0-1, who had received 0-1 prior regimens (without G or E) and no prior RT were enrolled to successive cohorts in a 3+3 design. Patients were treated in 21 day cycles with G IV days 1 & 8, E once PO QD, and twice daily RT fractions separated by at least 4 hours on days 1, 2, 8, and 9. Whole abdominal RT fields were used. Dosing cohorts were as follows (G in mg per m2, E in mg, XRT/fraction in cGy): 1 (1,000, 100, 40), 2 (1,000, 100, 50), 3 (1,000, 100, 60), 4 (1,000, 150, 60). Primary endpoint was to define dose limiting toxicity (DLT) and the maximum tolerated dose (MTD). Results: A total of 27 pts, (median age 64 yrs and 15 male), were enrolled between 11/24/08 and 4/12/12. 17 patients had a PS of 1. The majority of patients were stage IV. Seven pts were enrolled in dose level 1, with 1 pt experiencing a DLT of grade 3 ileus, 3 pts enrolled each in dose levels 2-4 without DLT and 11 pts enrolled in the expanded portion of level 4. Best response by RECIST in 24 evaluable pts and was as follows: partial response 8, stable disease 15 and progressive disease 1. One pt initially found to be unresectable at surgery was subsequently resected with only minimal microscopic residual disease. The majority of grade 3 toxicities were hematologic with 1 grade 5 bowel perforation in dose level 1 in cycle 4. Conclusions: This phase I study combining low-dose hyperfractionated RT as a sensitizer to full dose G plus E was well tolerated with the majority of pts experiencing either a partial response or stable disease. This represents a novel strategy worthy of further investigation in pts with advanced PC. Clinical trial information: NCT00761345.
Local control in resectable and borderline resectable pancreatic cancer (PCa) treated with preoperative chemoradiation using IMRT or chemotherapy alone.
Authors: Kharofa Jordan , Kelly Tracy R. , George Ben , Ritch Paul S. , Tsai Susan , Christians Kathleen K. , Evans Douglas B. , Erickson Beth 
Published: February 2017

282 Background: The primary objective is to review local control and failure patterns in PCa patients treated with preoperative chemoradiation (chemoXRT) using IMRT compared to patients treated with chemotherapy alone. Methods: All patients with resectable and borderline resectable PCa treated between 1/1/2009 -11/1/2011 were reviewed. During the study period, 68 patients (40 borderline resectable, 28 resectable) were treated with preoperative chemoXRT (50.4 Gy [1.8 Gy/fx] with concurrent gemcitabine [n=59] or capecitabine [n=7]). 12 patients with resectable tumors received gemcitabine based chemotherapy alone and did not receive radiation therapy due to enrollment on chemotherapy only protocols (n=10) or to patient preference (n=2). Radiation was delivered to a CTV that includes the primary mass, the SMA and SMV, +/- the celiac axis. A 4D-CT and daily image guidance were used in all patients. The local failure free interval was defined as the time from surgical resection to local failure or last documented CT scan of the abdomen with no evidence of local disease progression. Results: Following preoperative chemoXRT, 48/68 patients underwent resection with 47(98%) R0 resections. 11/12 patients in the No XRT group undwerent resection with 10 (91%) R0 resections. In the No XRT group, 8/11 (73%) patients failed locally at the SMA/SMV or resection bed as a component of first failure compared to 1/48 (2%) patients who received preoperative chemoXRT (p<0.001). Local failure was the sole site of first failure in 5/11 patients in the No XRT group and 0/48 patients who received preoperative chemoXRT. The actuarial rate of local failure 1 year from surgery was 5% in the preoperative chemoXRT group vs 27% in the No XRT group (p<0.001). All local failures in the No XRT group would have been encompassed using the CTV target volumes used in patients treated with preoperative chemoXRT. Conclusions: IMRT-based, conformal, preoperative chemoXRT for resectable and borderline resectable PCa may facilitate margin negative resection and increase local control. Omission of radiation therapy may result in high rates of local failures at the SMA/SMV vasculature or in the pancreatic bed.
High-volume centers for pancreatic cancer surgery: Does the media message matter?
Authors: Chau Zeling , Smith Jillian K , West James K. , Zhou Zheng , McDade Theodore P. , Ng Sing Chau , Whalen Giles Francis , Moser Arthur J. , Tseng Jennifer F. 
Published: February 2017

297 Background: Hospital procedure volume is associated with pancreatic cancer outcomes. However, differences between high-volume hospitals are less clear. Furthermore, consumers are barraged with grading systems for hospitals, whose relationship to volume and real outcomes are poorly delineated. Methods: Massachusetts Division of Health Care Finance and Policy Hospital Inpatient Discharge Database was queried to identify 5 highest-volume hospitals performing resection for pancreatic cancer 2005-2009. Primary outcomes included mortality, complications, median length of stay (LOS) and composite outcomes score (COS) including above. Ranks were determined for each outcome and compared to procedure volume order (highest to lowest), as well as ratings identified from popular media and internet-based hospital ratings including US News and World Reports (USN) Consumer Reports (CR), Healthgrades (HG) and Hospital Compare (HC). An inter-rater reliability analysis was performed with Spearman’s rank correlation coefficients calculated between outcomes and ratings. Results: 5 hospitals performing 82% (n=681) of statewide resections for pancreatic cancer were identified. In-hospital mortality ranged from 0-5.1%, complications 9.0-32.0%, median LOS 7-11 days. Within 5 highest-volume centers, outcomes did not improve in a consistent linear fashion with increased volume; however, volume remained more correlated with outcomes than consumer ratings. Of consumer ratings, HG ratings were most correlated with mortality, but had Spearman correlation coefficient of only 0.32. Complication measures were correlated with HG and USN equally at 0.22. USN rankings were highly correlated with LOS measures at 0.85. When all outcome measures were combined, HG was most correlated at 0.32. CR ratings were inversely correlated with all outcome measures. Conclusions: Between high-volume hospitals, outcome variation exists that does not completely correlate with either absolute volume numbers or by popular media grading systems, which can be discordant. Both consumer-directed ratings and volume data, where available, should be used only in appropriate contexts to direct patient care.
Analysis of recurrence after resection of pancreatic neuroendocrine tumors.
Authors: Newman Naeem A , Mann Gary N. , Shukla Mrinal , Swett Katrina R , Levine Edward A. , Bergquist John , Park James Oh , Pillarisetty Venu Gopal , Sham Jonathan G , Shen Perry 
Published: February 2017

304 Background: Outcomes after recurrence of resected pancreatic neuroendocrine tumors (PNETs) are not well described. Our aim is to assess the rate and sites of recurrence and its effect on clinical outcomes. Methods: Retrospective chart review of patients (n= 80) who underwent surgical resection of PNETs at two institutions. Patients were treated from September 2002 to July 2010. Charts were reviewed for disease recurrence, date, site, and treatment of recurrence. Results: There were a total of 14 (17.5%) recurrences. The most common site of recurrence was the liver (10 patients, 71.4%). The most common treatment of recurrences was chemotherapy (5 patients, 35.7%). The 1, 3, and 5 year disease-free survival (DFS) was 90.9%, 82.7%, and 72.5% respectively. Median recurrence free survival (RFS) was 127 months. The median follow-up for all PNET patients was 25.8 months (range 1 to 140 months). Three-year survival was 97%. Local, distant, and combined recurrences occurred in 7.5%, 12.5%, and 5% of all patients, respectively. Multivariate analysis found AJCC stage (p=0.03) to be an independent predictor for DFS. Median follow-up of patients after they were found to have a recurrence was 13.8 months. Three-year survival for those with and without recurrence was 96.3% and 100%, respectively (p=0.36). Conclusions: AJCC stage is a significant predictor of recurrence after resection of PNETs with hepatic metastases being most common. Survival of patients with recurrence is not significantly different from patients without recurrence and is likely due to the indolent nature of the disease.