bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of adjuvant chemoradiotherapy with survival in patients with resected gallbladder carcinoma: A systematic review and meta-analysis.
Authors: Chie Eui Kyu , Kim Byoung Hyuck , Kwon Jeanny , Kim Kyubo 
Published: January 2019

477 Background: The impact of adjuvant radiotherapy (ART) on survival in gallbladder carcinoma (GBC) remains underexplored, and conflicting results have been reported. We conducted a systematic review and meta-analysis to clarify the impact of ART in GBC. Methods: Systematic literature search was performed in the several databases following the PRISMA guidelines from inception to August 2016. We included the studies which reported survival outcome in the patients with or without ART following curative surgery. Results: Fourteen retrospective studies including 9364 analyzable patients met all inclusion criteria, but most of them had a moderate risk of bias. Generally, ART group had more patients with unfavorable characteristics than the surgery alone group. Nevertheless, pooled results showed that ART significantly reduced the risk of death (HR, 0.54; 95% CI, 0.44-0.67; p < 0.001) and recurrence (HR, 0.61; 95% CI, 0.38-0.98; p = 0.04) compared to the surgery alone group. Exploratory analyses demonstrated that subgroup of patients with lymph node positive disease (HR, 0.61; p < 0.001) and R1 resection (HR, 0.55; p < 0.001) had survival benefit from ART, while those with lymph node negative disease did not (HR 1.06; p = 0.78). No evidence of publication bias was found (p = 0.663). Conclusions: This work is the first meta-analysis evaluating the role of ART and provides convincing evidence that ART may offer survival benefit, especially in high risk patients. However, further confirmation with a randomized prospective study is needed to clarify the subgroup of GBC patients who would most benefit from ART.
Downstaging of unresectable intrahepatic or hilar cholangiocellular carcinoma by selective intra-arterial floxuridine and systemic cisplatin and gemcitabine. A dose finding single center phase IIa study.
Authors: Pietge Heike 
Published: January 2019

478 Background: Patients with unresectable cholangiocarcinomas (CCC) have a poor prognosis even if palliative systemic chemotherapy is offered. A combined approach of systemic and intrahepatic chemotherapy may improve local control rates and allow downstaging. The aim of the study was to determine the maximum tolerated dose (MTD) of systemic intravenous gemcitabine in combination with intravenous cisplatin and hepatic arterial infusion with floxuridine in patients with unresectable intrahepatic or hilar CCC. Safety, toxicity, response rates and resectability rates after 3 months of combination treatment are reported. Methods: 12 patients were treated within a 3+3 dose escalation algorithm with 600, 800 or 1000 mg/m2 gemcitabine and a fixed dose of cisplatin 25 mg/m2 systemic chemotherapy on day 1, 8 every 3 weeks for 4 cycles and floxuridine 0,2 mg/kg on day 1-14 continous hepatic intra-arterial chemotherapy every 4 weeks for 3 cycles. PET/CT and/or CT scan was performed after 12 weeks. Results: The MTD of gemcitabine was 800 mg/m2 in this setting. Dose-limiting toxicities were recurrent biliary tract infections (n = 1) and neutropenic fever (n = 1). Response rates were: 27% partial remission and 73% stable disease. Although none of the patients achieved resectability after 3 months, 3-year-overall survival (OS) was 33%, median OS 21,9 months (1-49) and median progression-free survival 10,5 months (2-40). Conclusions: Combination of systemic gemcitabine and cisplatin plus intraarterial floxuridine is feasible and appears effective in disease control, but achievement of resectability seems challenging. Randomized trials comparing this combination to gemcitabine/cisplatin alone are warranted. Clinical trial information: NCT01692704.
Can looking at density differences between liver parenchyma and oligometastatic lesions predict outcomes and toxicities in patients receiving stereotactic body radiation therapy for metastatectomy?
Authors: Jin Will , Toesca Diego Augusto Santos , Osmundson Evan , Shaffer Jenny , Koong Albert , Chang Daniel Tandel 
Published: January 2019

479 Background: Stereotactic body radiation therapy (SBRT) has found utility in oligometastatic liver lesions by providing excellent local control in most patients. These tumors are not routinely biopsied to evaluate for histologic grade due to high risk of seeding. Non-invasive pre-treatment radiographic findings may be able to identify a subset of patients at higher risk of local recurrence. Methods: Retrospective review of an IRB-approved database of liver metastases treated with SBRT yielded 55 patients for final analysis. Liver parenchyma and metastatic liver lesions were contoured using MIM version 6.6.5. Receiver Operating Characteristic curves and mean values were used to generate binary cutoffs for toxicities and Kaplan-Meier analysis, respectively. Computer Tomography features, like density, skew, kurtosis, variance, and volume, based on our pre-SBRT planning liver protocol images and their relationship with outcomes and toxicities were examined. Results: Largepre-SBRT density differences between oligometastatic lesions and liver parenchyma, as measured by Hounsfield Units, was associated with a 3.248 increased risk of local failures (p = 0.027) and grade 3 or higher late non-hepatobiliary toxicities (p = 0.032). There were no associations with overall survival. Lesions with large variance in density was associated with grade 3 or higher acute hepatobiliary toxicities (p = 0.043). Conclusions: Density metrics in metastatic liver lesions are readily available in most treatment planning systems and may be a prognostic indicator of tumor aggressiveness. Higher radiation doses may be needed to reduce rates of local recurrence in these patients. Further studies should examine if post-treatment density metrics are dose-dependent and correlate with outcomes.
The role of stereotactic body radiation therapy using the CyberKnife system in limited hepatic metastases.
Authors: ElAlfy Eman , Doyen Jerome , Bondiau Pierre-Yves 
Published: January 2019

481 Background: CyberKnife has shown increasing evidence supporting its use for liver metastases with high rates of local control (LC) and low toxicity. we aim to investigate its safety and efficacy for patients with limited hepatic metastases. Methods: 48 patients (pts) with 63 metastatic liver lesions were treated with Cyberknife between March 2007 and November 2012. Most of pts were aged more than 65 years (ys) (n = 25) and males (n = 25). ECOG Performance status was 2 in 20 pts and 1 in 17 pts. Primary tumors were from GIT (n = 34), breast (6), ovary (2), choroidal melanoma (2), lung (1), kidney (1), thyroid (1) and CUP (1). Number of lesions treated per pt was 1 in 36, 2 in 9 and 3 in 3. GTV volume ranged from 0.81 to 164.07 cm³ (median = 22.53). Median volume of PTV was 23.73 cm³ and mean was 44.11 cm³ (range 2.03 - 215.40). We do not use margin (CTV = GTV). Dose per fraction ranged from 5 Gy to 15 Gy, median total dose was 43.5 Gy (range 25 - 45) in 3 fractions (3-5) and 143 beams prescribed to 80 % isodose line. The delivered median min GTV dose was 39.01 Gy and the prescribed median min PTV dose was 35.55 Gy. Results: Treatment was well tolerated with minimal grade 1 toxicity. 2 acute toxicities as nausea, asthenia and moderate colics. No Grade 3 or higher toxicity. Median follow-up was 11.9 months, overall survival (OS) was 83.6% and 57% at 1 and 2 yrs respectively, disease free survival (DFS) was 69.5% and 46.1% at 1 and 2 yrs and LC was 76.3% and 57.9% at 1 and 2 yrs. OS influenced by; Age < 65 years (P = 0.033), Males (P = 0.050), PTV volume < 50 cm3 (P = 0.002), Coverage > 95% for GTV (P = 0.041). Factors affected DFS were ; Age < 65 years (P = 0.034), Males (P = 0.017), Total dose of 45 Gy (P = 0.001), Dose per fraction equal to 15 Gy (P = 0.001), P.S = 2 (P = 0.024), Max dose > 55 Gy for GTV (P = 0.000), CTV (P = 0.000), PTV (P = 0.000), coverage > 95% for GTV (P = 0.048), CTV (P = 0.031), PTV (P = 0.001), min dose > 35 Gy for GTV (P = 0.032), CTV (p = 0.013), LC affected by; Females (P = 0.013). min dose > 35 Gy for PTV (P = 0.05). Conclusions: Cyberknife is an effective modality with good LC and minimal side effects for limited hepatic metastases. We recommend further studies to define the role of combined modality treatment, clarify treatment parameters and illustrate the related quality of life.
Patterns of failure in a phase II trial of neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT) for resectable and borderline resectable (BLR) pancreatic cancer.
Authors: Kharofa Jordan , Mierzwa Michelle Lynn , Olowokure Olugbenga Olanrele , Sussman Jeffrey J. , Latif Tahir , Gupta Anumeha , Esslinger Hope , Poreddy Sampath , Mcgill Brian , Wolf Eric , Smith Milton T , Choe Kyuran Ann , Ahmad Syed A. 
Published: January 2019

482 Background: There is emerging interest in the role of SBRT in locally advanced pancreas cancer, however little prospective data exists examining the safety, efficacy, and optimal target volumes for SBRT in the neoadjuvant setting for resectable or BLR pancreatic cancer. Methods: Eighteen patients were enrolled from 11/2014-6/2017. SBRT was delivered to the tumor and abutting vessel with fiducials/compression and a 3 mm PTV margin to 33 Gy (6.6 Gyx5fxn) with an optional elective PTV to 25 Gy (5 Gyx5fxn) customized to the nodal space and mesenteric vessels. Patients without progression underwent surgery 4-6 weeks following SBRT. The primary endpoint is ≥ Grade 3 acute and late GI toxicity. Secondary endpoints included overall survival (OS), progression-free survival (PFS),and cumulative incidence of local failure (LF). LF is defined as recurrence within conventional RT volumes from the time of resection to local failure or last CT with no progression. Local failures were fused to planning CTs for dose quantification. Results: Thirteen patients had BLR tumors due to arterial abutment (n = 7) or SMV encasement (n = 8); 3 patients had resectable tumors. All patients received 4 months of gemcitabine/nab-paclitaxel (n = 13) or FOLFIRNOX (n = 5) prior to SBRT. There were no ≥ Grade 3 acute or late GI events. Metastases were noted in 6 patients (33%) at restaging or surgery. Surgery was performed in 12 patients (67%) with 11 (92%) R0 resections. Median OS and PFS are 21 months and 11 months, respectively. Progression occurred in 67% (8/12) of resected patients with first site of failure as distant (n = 3, 38%), local only (n = 4, 50%), and local and distant (n = 1,13%). The cumulative incidence of LF at 12 months from resection was 50%. All LF were outside to the PTV33 with median D90 of 11.5 Gy (4-25 Gy), V25 Gy of 51% (0-90%), and V33 Gy of 45% (0-52%). Conclusions: SBRT as a component of neoadjuvant therapy was well tolerated. However, local failures were predominantly observed outside the PTV33 volume within conventional RT volumes. Therefore, the durability of local control after SBRT in the neoadjuvant setting relative to chemoradiation merits close examination. Clinical trial information: NCT02208024.
Impact of molecular tumor board on late-stage gastrointestinal malignancies at a tertiary center.
Authors: Cannon Timothy Lewis , Murphy Jo-Ellen , Carter Jennifer , Trump Donald L. , Elkin Sheryl Krevsky , Asif Anam , Knopp Laura , Jessup John Milburn 
Published: January 2019

483 Background: Inova Schar Cancer Institute formed a molecular tumor board in early 2016 to identify treatment options for patients with gastrointestinal malignances based on molecular testing and to track outcomes. Methods: From March 2016 to June 2017, 78 patients with advanced gastrointestinal malignancies were presented at our molecular tumor board. The most common mutations, the percentage of patients who received targeted therapies, responded to targeted therapies, died or went on hospice prior to receiving a recommended therapy, and had an available Association of Molecular Pathology Tier 1 or Tier 2 recommendation available were reviewed retrospectively. We also compared the overall survival of patients who received a new treatment after MTB compared to those who did not. N-of-One, Inc. provided curation of molecular testing and participated in the MTB. Results: 78 patients with gastrointestinal cancers were presented between March 2016 and June 2017. Thirteen (19%) patients received targeted therapy and 31% had partial response, 15% had Stable Disease, and 54% had progression of disease. 12 patients (15%) died or went on hospice before recommendations could start and 11 patients (14%) are waiting to start recommended therapy. 38 (49%) patients did not have a mutation that prompted a MTB recommendation. Median OS of the 33 patients who started a new therapy (including chemotherapy or unrelated clinical trials) after MTB was 15.3 months vs. 11.5 months in 40 patients who continued current therapy (P = 0.016 Wilcoxon). The three most common mutations detected were TP53, KRAS, and APC. The majority of cases had more than one variant. 18% of cases had a variant classified as Tier 1; 74% of cases had a variant with the highest AMP classification of Tier 2. Conclusions: The majority of patients with Gastrointestinal malignancies presented to the Inova MTB had a finding that supported a molecularly-guided therapy, with a small but meaningful number of partial responses. Barriers to the use of molecular guided therapy included molecular testing and presentation at a late disease stage, and alternative chemotherapeutic options.
Everolimus and transarterial embolization (TAE) for hepatic metastasis in neuroendocrine tumors (NET).
Authors: Chauhan Aman , Magee Gray , Horn Millicent , Khouli Riham , Weiss Heidi , Krohmer Steven J , Anthony Lowell Brian 
Published: January 2019

485 Background: TAE of hepatic metastases is effective loco-regional therapy for neuroendocrine tumor (NET) patients. Transarterial chemotherapy (TACE) and transarterial radiotherapy (TARE) are other options in controlling hepatic metastases but deliver cytotoxic agents only at the time of the procedure. Systemic therapies such as everolimus or sunitinib are often held 2-4 weeks prior to and after the procedure. We hypothesize that concurrent oral treatment with everolimus and transarterial hepatic embolization is safe. Methods: Medical records of all NET patients (pts) treated at the Markey Cancer Center between July 2016 to July 2017 with concurrent transarterial embolization and everolimus were reviewed. Results: Total number of pts eligible for analysis was 15. Mean age of study cohort was 57.5 years (31-77). Seven pts were small bowel, 4 were pancreatic and remaining 4 were unknown NET primaries. Nine patients had grade 1 (Ki 67 < 2%) and 6 patients had grade 2 NETs (Ki-67 between 2-20%). Mean duration of treatment with everolimus prior to embolization was 3.8 months and mean dose was 10 mg orally every other day. Mean days of hospitalization were 1.46. Eleven (73%) pts were discharged the day after procedure. Ten (67%) pts reported nausea, 9 (60%) reported abdominal pain, 5 (30%) reported emesis. One patient had hematemesis immediately post procedure. Thirteen (87%) pts had no significant change in hemoglobin pre and post procedure (within one numerical point). No patient developed infectious complications. Conclusions: Combining everolimus with TAE is safe and does not result in longer hospitalizations or toxicities greater than that expected from TAE alone.
Palliative care and end-of-life health utilization in elder patients with pancreatic cancer.
Authors: Bhulani Nizar , Gao Ang , Gupta Arjun , Li Jenny Jing , Guenther Chad , Ahn Chul , Paulk M. Elizabeth , Houck Stephanie , Beg Muhammad Shaalan 
Published: January 2019

488 Background: Prospective trials have shown that palliative care is associated with improved survival and quality of life, with lower rate of end-of-life health care utilization and cost. We examined trends in palliative care utilization in older pancreatic cancer patients. Methods: Pancreatic cancer patients with and without palliative care consults were identified using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database between 2000 and 2009. Trend of palliative care use was studied. Emergency room and Intensive Care utilization and costs in the last 30 days of life were assessed. Statistical analyses were performed with SAS version 9.4 (SAS Institute, Inc., Cary, NC). Results: Of the 72205 patients with pancreatic cancer, 3383 (4.1%) received palliative care. The proportion of patients receiving palliative care increased from 1.8% in 2000 to 7.8% in 2009 (p for trend < 0.001). Patients with palliative care were more likely to be Asian and women. Of those who received palliative care, 73% received it in the last 30 days of life, and only 11% at least 12 weeks before death. The average number of visits to the ED in the last 30 days of life were significantly higher for patients who received palliative care (0.93±0.62) versus those who did not (0.79±0.61), p < 0.001, and had a significantly higher cost of care ($1317 vs $842, p < 0.001). Intensive care unit length of stay in the last 30 days of life did not differ between patients who did and did not receive palliative care (1.14 days vs 1.04 days, p 0.08). Intensive care unit cost of care was significantly higher for patients with palliative care compared to their counterparts ($5202.641 vs $3896.750, p < 0.001). Conclusions: Palliative care use for pancreatic cancer patients has increased between 2000 and 2009 in this study of Medicare patients. However, it was largely offered close to the end of life and was not associated with reduced health care utilization or cost. Early palliative care referral may be more beneficial.
The pathway regulating RhoA activity to predict the survival of gastric cancers.
Authors: Gao Jing , Huang Wenwen , Mu Shuo , Zhao Songhui , Zhang Shuirong , Zhang Peng , Ge Sai , Li Zhongwu , Zhang Cheng , Yao Ming , Liu Zhenzhen , Wang Kai , Shi Weiwei , Shen Lin 
Published: January 2019

49 Background: RhoA mutation has been intensively studied for its association with progression in gastric cancer (GC). Recently, mutations in a pathway regulating RhoA activity have been identified as a predictive biomarker in breast cancer. Herein, our aim is to investigate the role of such pathway in the progression of patients with GC receiving chemotherapies. Methods: Two non-overlapped TCGA cohorts (TCGA1, downloaded from GDC, N = 123 and TCGA2, from Cbioportal, N = 312) and a third ACRG cohort (Nature Medicine 2015, N = 295) were assessed for their mutation status of RhoA pathway; meanwhile, a cohort from Chinese GC (CGC, N = 57) was examined with whole exome sequencing (WES). A subset of “Regulation of RhoA activity” pathway (NCI Pathway Interaction), denoted as RhoA_S, was derived from analyzing the expression of RhoA and mutations in TCGA1 without referring to its survival data. Subsequently, RhoA_S was evaluated for its prediction of overall survival (OS) in the above four GC cohorts receiving chemotherapies. Results: GCs with wild-type of RhoA_S as well as gain-of-function of RhoA mutation where the function of RhoA remained active were compared against those with mutated RhoA_S. The frequencies for the mutant RhoA_S were 46.3%, 24.0%, 16.3% and 50.9% for TCGA1, TCGA2, ACRG and CGC, respectively; while the “active” RhoA_S were found more unlikely to respond to chemotherapies and significantly associated with poor clinical outcomes in all four cohorts. The hazard ratios and p-values were 0.513, 0.009 for TCGA1; 0.509, 0.02 for TCGA2; 0.6, 0.04 for ACRG and 0.229, 0.014 for CGC, respectively. Conclusions: Four independent GC cohorts (totally 787 patients) validated RhoA_S as a predictive biomarker for their survival. Not only have our results confirmed gain-of-function in RhoA mutant facilitates the progression of GC patients, but also indicated the regulators of RhoA activity are implicated in their overall survival. This study has provided us an option to extend potentially druggable targets in highly malignant cancers with poor prognosis like GC.
Retrospective single center review of toxicity and efficacy of a modified FOLFIRINOX regimen in patients with locally advanced and metastatic pancreatic cancer.
Authors: Pulluri Bhargavi , Skelly Joan , Barry Maura Meredith 
Published: January 2019

490 Background: Conroy et al. (N Engl J Med 364:1817–1825, 2011) have shown significantly better overall survival with FOLFIRINOX compared to gemcitabine in metastatic pancreatic cancer patients (MPC). However, given the toxicity associated with FOLFIRINOX treatment, different institutions have adapted varying modifications to the original regimen. Methods: We performed a retrospective review of dose, toxicity, and efficacy of FOLFIRINOX in patients with unresectable locally advanced pancreatic cancer (LAPC) and MPC treated between Jan 2011 and Dec 2015 at University of Vermont Medical Center. Results: 43 patients were treated, of which 33 did not receive any prior treatment (6 LAPC, 27 MPC). 41 patients received dose attenuation with 1st cycle. Median relative dose of irinotecan, oxaliplatin and 5-FU were less than reported by Conroy (69 vs. 81%, 70 vs. 78% and 71 vs. 82%). Median number of treatment cycles 7.8 (range 1 to 41). Median progression free survival in our MPC cases compared to Conroy’s data was 5.7 vs. 6.4 months; overall survival at 6 and 12 months were 78 vs. 75.9% and 41 vs. 48.4% respectively. Grade ¾ toxicities were less, including neutropenia (p<0.001), fatigue (p =0.01) and neuropathy (p=0.04). One patient had grade 3 pneumonitis related to oxaliplatin. Conclusions: Our findings suggest that dose attenuation of 5-FU, irinotecan and oxaliplatin improve tolerability with fairly similar outcome as reported by Conroy et al. [Table: see text]
Is there any survival benefit of additional chemotherapy (C) following adjuvant C in pancreatic cancer (PC) patients (pts) with postsurgery elevated CA19-9?
Authors: Saif Wasif M. , Smith Melissa H , Goodman Martin D. , Russo Suzanne M. , Huber Kathryn , Salem Ronald R 
Published: January 2019

491 Background: Pancreatectomy offers only potential for cure but is only possible in a minority of pts. Even in those pts who receive adjuvant C, majority of them succumb to death due to metastases. RTOG 9704 showed that post-surgery CA 19-9 levels are an important predictor of survival. ESPAC-3 showed that completion of all 6 cycles of adjuvant C was an independent prognostic factor. Any survival benefit of an intensified C strategy has not been demonstrated in pts with persistently ↑ CA19-9. The object of this study was to investigate any benefit of additional C following adjuvant in these pts. Methods: 25 pts with R0 surgery of PC who received adjuvant C with post-surgery ↑ CA 19-9 but no radiographic evidence of cancer were identified between 2005-2017. Either biopsy or PET scan determined recurrence of PC. Efficacy endpoints were overall survival (OS) and disease-free survival (DFS). Results: The Table summarizes results. Additional C included 5-FU, capecitabine, platins, irinotecan and nab-paclitaxel. CA 19-9 normalized in 3 pts while 22 remained ↑ or further ↑. Two pts underwent metastatectomy. Median DFS was 14.5m (9-18), OS 29m (19-96) and OS rates were 80 %, 50 % at 1 and 2 years respectively. Conclusions: We believe that the longer OS of our pts with ↑ CA 19-9 post-surgery was due to additional C following adjuvant C, close monitoring with monthly CA19-9 and 3-monthly CT scans. Our study also underlines importance of collecting pre-surgery CA19-9 and complete staging including chest. Prospective study aiming to evaluate role of maintenance or intensified C are indicated.[Table: see text]