bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison between the three oxaliplatin-based regimens with bevacizumab in patients with metastatic colorectal cancer.
Authors: Ohhara Yoshihito , Suenaga Mitsukuni , Matsusaka Satoshi , Shinozaki Eiji , Mizunuma Nobuyuki , Yamaguchi Toshiharu , Hatake Kiyohiko 
Published: February 2017

687 Background: XELOX (capecitabine/L-OHP) therapy that includes orally administered ﬂuoropyrimidine instead of infusional fluorouracil (5-FU) was approved for metastatic colorectal cancer (mCRC) in Sep 2009 in Japan. A pivotal trial (NO16966 study) demonstrated the non-inferiority of XELOX to FOLFOX (5-FU/L-OHP/LV) and the superiority of those L-OHP-based regimens plus bevacizumab (BV) to those without in the first-line treatment of mCRC. We evaluated the safety and efficacy of XELO+BV compared with FOLFOX4 or mFOLFOX6 plus BV in the first-line treatment for mCRC patients at a single institute. Methods: Between Jun 2007 and Nov 2008, 85 patients received FOLFOX4+BV (FF4 arm), between Dec 2008 and Sep 2009, 40 patients received mFOLFOX6+BV (FF6 arm), and between Oct 2009 and Sep 2010, 60 patients received XELOX+BV (XELOX arm). The best overall responses were evaluated using RECIST 1.0 during chemotherapeutic treatment, and adverse events were graded according to CTCAE ver.3.0. Progression-free survival (PFS) was estimated by Kaplan-Meier methods. Results: Characteristics of patients of FF4 arm, FF6 arm, and XELOX arm were below: median age, 60 yr vs. 62 yr vs. 60.5 yr; gender (male), 48.2 % vs. 62.5 % vs. 58.3%. The overall response rates (CR+PR) were 61.1 %, 72.5 %, and 75 % (95% CI; 50.6-71.8%, 58.0-87.0%, and 63.7-86.3%). Median PFS were 17.0 months, 15.5 months, and 14.4 months, respectively (cut-off: Aug 31, 2011). There were no statistical significances not only between FF4 arm and FF6 arm (log-rank; p=0.641), but also between XELOX arm and FF4+FF6 (FOLFOX) arm (log-rank; p=0.138). FOLFOX arm was associated with higher incidence of grade 3/4 neutropenia than XELOX arm. Grade3 diarrhea and hand-foot syndrome (HFS) were more frequent in XELOX arm. Conclusions: This study suggests that XELOX arm was equal to FOLFOX arm, regardless of regimen, in tumor response and PFS. Further follow-up is necessary to confirm the benefit on survival.
Cardiotoxicity of 5-fluorouracil in patients with gastrointestinal cancer.
Authors: Lopez Lourdes , Montenegro Paola Catherine 
Published: February 2017

689 Background: 5-fluorouracil (5-FU) is a agent of chemotherapy that has been associated with cardiotoxicity infrequently. The reports shown incidence of clinically apparent 5-FU cardiotoxicity in 1.6% for patients receiving 5-FU alone or in combination with another agents. Methods: We investigated the clinical characteristics of 5-FU cardiotoxicity in patients with gastrointestinal cancer treated in instituto nacional de enfermedades neoplasicas (INEN) Lima - Peru between October 2009 and October 2010. Results: Between October 2009 and October 2010, were evaluated 240 cases with gastrointestinal cancer treated with 5-FU alone or plus combinations with another chemotherapy agent, 8 cases (3.3%) had cardiotoxicity. 37.5 % had history of cardiovascular disease, 3 patients had a history of hypertension and 1 patient diabetes mellitus plus hypertension. 50% (4 patients ) had normal EKG prior to treatment, 25% (2 patients) had no EKG, In 12.5% (1patient) had sinus tachycardia and another patient had ventricular extrasystoles were detected. After chemotherapy infusion 75% (6) had changes in the EKG. In 8 patients was observed as the main symptom chest pain with radiation to left arm or upper back, without elevated cardiac enzymes. 87.5% (7 patients ) had symptoms after 6 pm. And the duration of symptoms was 48 hours in 62.5% (5 patients), 12.5% (1patient ) in 24 hours and 6 hours in 12.5% (1 patient). One patient died of acute heart failure and had history of hypertension and diabetes mellitus and received the combination cisplatin - 5-FU. Conclusions: The eight cases reports confirm the potential cardiotoxicity of 5-FU and argues the need for cardiovascular assessment by a specialist before the start of treatment in addition to cardiac monitoring in patients during treatment, especially in patients with risk factors especially in the first cycle, women and at night. The mechanism of 5-FU cardiotoxicity is not fully elucidated. Coronary spasm is the most accepted hypothesis.
Laparoscopic gastrectomy for gastric adenocarcinoma: A single institution’s experience and oncologic outcomes of 65 consecutive patients.
Authors: Arrington Amanda Kathleen , Ho Joyce , Kim Joseph , Trisal Vijay , Ellenhorn Joshua D. I. 
Published: February 2017

79 Background: The application of laparoscopy in the surgical treatment of gastric cancer has become more commonly utilized in recent years. Most of the published series are from Asia and few report on survival. Our objective was to elucidate the safety, efficacy, and oncologic outcomes of laparoscopic gastrectomy in patients with gastric adenocarcinoma. Methods: The medical records of all patients who underwent laparoscopic gastrectomy at City of Hope National Medical Center between 6/2005 and 8/2011 were retrospectively reviewed. Relevant data analyzed included patient demographics, operative parameters, complications, recurrence, and survival. Results: A total of 65 consecutive patients were identified. Of all laparoscopic procedures, 5 were proximal, 41 were distal, and 19 were total gastrectomies. Median age was 67 years (35-96). Median operative time was 370 min (228-583). Median EBL was 200 ml (10-900). Twenty-eight of the 65 laparoscopic gastrectomy cases employed robotic assistance in lymph node dissection. The median number of lymph nodes retrieved was 26. Forty-seven cases included D2 lymph node dissections, 16 cases were D1 dissections, and 2 cases involved D0 dissections. All intended D2 dissections had greater than 15 nodes retrieved. Median hospital stay was 7 days (3-39). Morbidity and mortality rates were 33% and 3%, respectively. Histological staging revealed most patients with Stage I or II disease. Median follow-up was 15 months (0.5 to 58). Cancer has recurred in 4 patients (6%). The 3-year overall survival for stage I disease (N=38) is 92%, stage II disease (N=17) is 71%, and for stage III (N=7) is 51%. Conclusions: The long-term oncologic outcomes and overall survival are comparable to that of open technique seen in other series. Our large institutional series shows that laparoscopic gastrectomy for gastric adenocarcinoma is feasible and safe and can be performed in patients with gastric cancer with excellent surgical and oncologic outcomes.
Definitive (chemo)radiotherapy in patients with esophageal cancer: A population-based study in northeast Netherlands.
Authors: Smit Justin Kendrick , Muijs Christina T. , Timmer Paul R. , Paardekooper Gabriel , Muller Karin , Woutersen Dankert , Mul Veronique E. , Beukema Jannet , Hospers Geke A. , Langendijk Johannes A. , Plukker John Theodorus 
Published: February 2017

83 Background: Definitive (chemo)radiation as primary treatment modality is offered to esophageal cancer (EC) patients, as an alternative for patients considered medically unfit for surgery or having irresectable tumors. We evaluated the results in our cohort to improve selection of patients for intensified non-surgical strategies and to identify which clinical factors have a prognostic impact on the overall (OS) and disease free survival (DFS). Methods: EC patients treated with definitive radiotherapy (RT) or chemoradiotherapy (CRT) from 4 radiotherapy referral centers between 1996 and 2008 were used. Only patients with squamouscellcarcinoma (SCC) or adenocarcinoma (AC) were included in the analyses. Results: In total 278 patients were identified of whom 106 (38.1%) were treated with CRT (platinum based, median 50.4 (46.8 – 70)Gy) and 172 (61.9%) with RT alone (median 60 (40-70)Gy). T- stage was cT1=5.6%;cT2=15.3%;cT3=60.9% and cT4=18.2%. Nodal stage consisted of cN0=35%;cN1=65%, including cM1a=5.8%. The male/female ratio was 78.3% to 21.7%. AC occurred in 57.6% and 42.4% had a SCC. The median age was 69 years. Median OS time was 11 (1-166) months with an OS of 45%, 22% and 6% and a DFS of 32%, 18% and 6% at 1, 2 and 5 years, respectively. There was no significant difference between the CRT and RT group in OS (p=0.09) and DFS (p=0.17). The DFS after 2 and 5 year was 25% and 12% for SCC patients versus 11% and 0% for AC patients (p=0.007). The OS at 2 and 5 year was 28% and 11% for SCC versus 14% and 0% for AC patients (p=0.020). Initial recurrence was seen locoregionally in 66.7% and distant metastases occurred in 33.3%. Common sites for distant recurrence were the liver with 52.4%, 17.5% bones and 15.5% lungs. Patients with SCC had a better response to (chemo)radiotherapy considering the OS (p=0.02, HR=0.7) and DFS (p=0.01, HR=0.69) in a multivariate analysis. Conclusions: Patients with a SCC esophageal tumor have better long-term results then AC patients after definitive (chemo)radiation. In this patient group SCC seems to be a strong prognostic factor for both OS and DFS. Furthermore the difference between RT and CRT is still small.
Effect of post-operative intra-abdominal infectious complications on overall and relapse-free survival following curative gastrectomy in patients with gastric cancer.
Authors: Tokunaga Masanori , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Terashima Masanori 
Published: February 2017

86 Background: The number of reports investigating the impact of postoperative complications on long-term outcome following curative gastrectomy is limited and still remains unclear. The aim of this study is to clarify the effect of postoperative intra-abdominal infectious complications on overall survival (OS) and relapse-free survival (RFS) following curative gastrectomy. Methods: Three hundred and sixty-seven patients pts who underwent curative gastrectomy for gastric cancer between June 2003 and December 2004 at Shizuoka Cancer Center were included. Clinicopathological features and effects of postoperative intra-abdominal infectious complications on OS and RFS were investigated. In this study, postoperative intra-abdominal infectious complications were defined as Clavien-Dindo grade II or more severe pancreas fistula, anastomotic leak, or intra-abdominal abscess. Results: Median age was 63 years, male-female ratio was 2:1. Pathological stage was Stage I; 225 patients, stage II; 72 patients, stage III; 64 patients, and stage IV; 6 patients. Median observation periods of survivors were 71 months. Of 367 patients, 32 patients (8.7%) had intra-abdominal infectious complications. Overall 5-year survival rate was significantly better in patients without complications than in those with complications (86.1 vs 67.9%, P<0.001). The same trend was observed even after stratification by pathological stage (Stage II; 76.9 vs 66.7%, P=0.254, Stage III; 62.1 vs 40.9%, P=0.218) although each difference was not statistically significant. Relapse free 5-year survival rate was significantly better in patient without complications (85.0 vs 64.9%, P=0.002), and the same trend was also observed after stratification by pathological stage. Conclusions: Postoperative intra-abdominal infectious complications adversely affect overall and relapse free survival of patients following curative gastrectomy. Reduced incidence of infectious complications may be beneficial to improve long-term outcome of patients with gastric cancer.
Patterns of failure following trimodality therapy for locally advanced esophageal cancer (EC).
Authors: Dorth Jennifer Anne , Willett Christopher , Czito Brian G. 
Published: February 2017

88 Background: Patterns of local-regional failure (LRF) after neoadjuvant chemoradiotherapy (CRT) and surgery for locally-advanced EC are poorly defined. Methods: This study reviewed pts treated with CRT followed by surgery for M0 esophageal cancer from 1995-2009. Staging and regional nodes (supraclavicular (SCV) through celiac) were defined based on AJCC 7th edition. Patterns of first failure were analyzed. LRF included: 1) initially involved nodal failure (INF), 2) initially uninvolved (subclinical) nodal failure (SNF), and/or 3) anastomotic. Abdominal para-aortic failure (PAF) at or below the superior mesenteric artery was scored separately. Isolated SNF or PAF was defined as no other local or distant failure. Actuarial local-regional control (LRC), event-free survival (EFS), and overall survival (OS) were estimated by the Kaplan-Meier method. Results: 156 patients were identified with a median age of 60 years. Primary location was upper in 1%, middle 17%, lower 32% and gastroesophageal junction (GEJ) 50% (Adeno: 79%; SCC: 21%). Staging included EUS (73%), CT (46%), and/or PET/CT (54%). 40% had stage II and 60% stage III disease. Concurrent CRT was primarily cisplatin/taxane and/or 5-FU-based. Primary RT fields (median dose: 45Gy) encompassed the tumor with an approximate 5 cm proximal and distal margin and included standard regional nodes. Boost fields (median total dose: 50.4Gy) encompassed gross disease with a 2 cm margin. Surgical technique was transhiatial (28%), Ivor-Lewis (47%), or tri-incisional (25%) with a median of 8 nodes dissected. Median f/u was 1.3 years. 2-yr LRC, EFS, and OS were 83%, 36%, and 49%. 2-yr SNF was 15% (n=14); anastomotic failure was 7% (n=7). SNFs were SCV (n=5), mediastinal (n=12), and/or celiac (n=3). 95% of SNFs were outside or near the margin of the primary RT fields. 2-yr isolated SNF was 3% (n=3), PAF was 11% (n=9), and isolated PAF 6% (n=5). Conclusions: SNF is the most common type of LRF after tri-modality therapy for locally-advanced EC. A limited subset of patients experience isolated SNF or PAF as first disease recurrence. The potential benefit of targeting additional SN or PA regions with RT is small and likely eclipsed by high rates of distant failure.
Chemoradiotherapy plus surgery versus surgery alone for resectable esophageal cancer: A systematic review of randomized control trials.
Authors: Njei Basile M. , Appiah Juliet , Ditah Ivo C. , Birk John W. 
Published: February 2017

94 Background: Several trials have demonstrated better survival when surgery is combined with neoadjuvant chemotherapy and concurrent radiotherapy (CRT) in the treatment of esophageal cancer (EC). However, it is unclear whether survival benefits are counterbalanced by a poor quality of life due to the adverse effects of the combination therapy. The aim of this study was to compare the efficacy and safety of CRT plus surgery versus surgery alone. Methods: Two authors independently conducted a comprehensive search of the Cochrane library PUBMED, MEDLINE, and published proceedings from major oncologic cancer meetings from January 1980 to July 2011. The titles and abstracts of all potentially relevant studies were screened for eligibility. In addition to overall outcome measures, subgroup analysis by histology of EC (squamous cell cancer [SCC] and adenocarcinoma [AC]), was also performed. Analysis was done using the fixed effect model. The Begg’s and Egger’s tests with visual inspection of the funnel plot were used to assess for population bias. Results: Fifteen studies involving 1,957 patients were included in the analysis. There was an overall statistically significant increase in the 5-year survival for the CRT plus surgery group versus the surgery only group (RR 1.47, 95% CI 1.24-1.76). By histological type, only patients with SCC showed prolonged survival: RR 1.53, 95% CI 1.26-1.85. We equally found an overall significant increase in grade 3 and 4 adverse events in the CRT plus surgery group compared to the group with surgery alone (RR 1.73, 95% CI 1.15-2.60). Again, a significant increase in serious adverse events was observed only in the sub-group of patients with SCC (RR 1.81, 95% CI 1.14-2.86). There was no evidence of heterogeneity or publication bias in these analyses. Conclusions: Overall, CRT plus surgery can improve long-term survival in EC patients. The results seem to be limited only to patients with SCC and not AC. However, the prolonged survival comes at the cost of poorer quality of life due to a higher incidence of adverse events. For the moment we recommend that the decision on what treatment strategy to use be based on informed patient preference.
Prostate cancer–specific mortality and competing causes of mortality among elderly men after local therapy for prostate cancer.
Authors: Mir Maria Carmen , Klink Joseph C. , Isariyawongse Brandon , Kibel Adam Stuart , Klein Eric A. , Stephenson Andrew J. 
Published: February 2017

103 Background: The benefit of definitive local therapy among elderly patients (> 65 years) with localized prostate cancer (PC) is uncertain, particularly for those with comorbid illness. Despite this uncertainty, the majority of these men currently receive local therapy. We analyzed the risk of prostate cancer-specific mortality (PCSM) relative to competing causes of mortality (CCM), stratified by disease severity and comorbidity, among contemporary men treated at two high-volume hospitals Methods: Between 1995-2005, 4237 consecutive men aged 65 years or older were managed by radical prostatectomy (N = 1634), external-beam radiotherapy (N = 1570), or brachytherapy (N = 1033) at Cleveland Clinic or Barnes-Jewish Hospital. Clinical information was obtained from prospective data bases. Comorbidity was assessed using ACE-27 and Charlson Comorbidity indices. PC risk was classified according to D’Amico criteria. Fine and Gray competing risk analysis was used to assess PCSM and CCM at 10 years. Results: Over a median follow-up of 72 months (IQR: 46-97), 88 and 748 PCSM and CCM events were observed. Among healthy men with low risk PC, 10 year PCSM was 2% and CCM was 19%. Among healthy men with high risk PC, PCSM was 11% and CCM was 27%. In the group with moderate-to-severe comorbidities, CCM was 49, 59%, and 58% and PCSM was 1%, 3%, and 21% among those with low-, intermediate- and high-risk PC, respectively. Among these unhealthy men, 26% were treated by radical prostatectomy, of whom 45% had low-risk PC and 16% had high-risk PC. Among healthy men, 41% were treated by radical prostatectomy, of whom 54% and 9% had low- and high-risk PC, respectively. Conclusions: The risk of PCSM vs. CCM for older men is low, particularly for those with moderate-to-severe comorbidity; 49-59% had died from CCM within 10 years. Current evidence suggests that local therapy for PC is associated with a 25% reduction in PCSM, at best. Thus, with active surveillance, it is unlikely that PCSM would exceed 5-7% in those with low- and intermediate-risk PC. These results should inform elderly men and physicians about the risk of PCSM and CCM when deciding upon treatment for localized PC.
Long-term results of MRI-guided partial prostate brachytherapy for favorable-risk prostate cancer: Implications for focal therapy.
Authors: Nguyen Paul Linh , Chen Ming-Hui , Zhang Yuanye , Tempany Clare M. , Cormack Robert A , Beard Clair , Hurwitz Mark D , Suh W. Warren , D'Amico Anthony Victor 
Published: February 2017

114 Background: To report long-term results of MRI-guided partial prostate brachytherapy and propose a definition of biochemical failure following focal therapy Methods: From 1997-2007, 318 men with cT1c, PSA < 15, Gleason ≤ 3 + 4 prostate cancer received MRI-guided brachtherapy in which only the peripheral zone was targeted. To exclude benign PSA increases due to prostatic hyperplasia, PSA failure was defined as nadir + 2 with PSA velocity >0.75 ng/mL/year. Cox multivariable analysis was used to determine factors associated with PSA failure. Results: After a median follow-up of 5.1 years (interquartile range: 2.8 to 7.3, maximum 12.1), 26 men failed. While 36 patients met nadir+2 criteria, all eight biopsy-proven local recurrences were among the 26 men who also had a PSA velocity >0.75 ng/mL/year. On multivariable analysis, having intermediate vs. low-risk disease (adjusted HR: 4.4 [95%CI: 1.3-5.5], p<0.001) was the only factor significantly associated with an increased risk of PSA failure. PSA failure-free survival at 5 and 8 years was 95.6% and 90.0% for low risk, and was 73.0% and 66.4% for intermediate risk, respectively. Conclusions: MRI-guided brachytherapy targeting the peripheral zone produced comparable cancer control rates to whole-gland treatment in men with PSA-detected low-risk disease, but may not be adequate for men with “favorable” intermediate-risk disease. Requiring a PSA velocity>0.75 in addition to nadir+2 may be a more appropriate way to define biochemical failure after therapies that target less than the whole gland.
Association of nuclear accumulation of p53 with ERG fusion and poor prognosis in prostate cancer.
Authors: Minner Sarah , Krohn Antje , Sirma Hueseyin , Simon Ronald , Graefen Markus , Sauter Guido , Schlomm Thorsten 
Published: February 2017

124 Background: We have previously shown that nuclear accumulation of p53 is rare in prostate cancer but strongly linked to early biochemical recurrence (Schlomm et al., Modern Pathology, 2008). The current study was designed to study the association between ERG fusion and p53 in a large series of prostate cancers. Methods: A prostate cancer tissue microarray (TMA) was constructed from 4,699 radical prostatectomie specimens with histological, pathological, and clinical follow-up data. Immunohistochemistry was applied to detect nuclear p53 accumulation as a marker for defective p53 and to detect ERG expression as a surrogate for ERG gene fusion. Results: Nuclear accumulation of p53 was detected in 62/3,667 (1.7%) analyzable tissue spots. Positive staining was significantly linked to advanced tumor stage (p<0.0001), high Gleason score (p<0.0001), presence of lymph node metastases (p=0.0005), and early PSA recurrence (p<0.0001) in all cancers. ERG expression was found in 1,990/4,266 (46.6%) analyzable cancers, but was unrelated to tumor phenotype or patient prognosis. Results of both p53 and ERG were available from 3,392 tumors. Presence of nuclear p53 staining was linked to ERG fusion positive cancers: 40 (2.7%) of 1,491 ERG-positive cancers, but only 20 (1.1%) of 1,901 ERG-negative tumors showed nuclear p53 staining (p=0.0004). A Kaplan-Meier survival analysis of p53 in the subsets of 1,699 ERG positive and 1,280 ERG negative cancers revealed that nuclear p53 accumulation was strongly linked to early PSA recurrence in both subsets (p<0.0001 each). Conclusions: These data demonstrate that the poor prognosis of prostate cancer patients with nuclear p53 accumulation is independently from the ERG fusion status, but suggest a distinct biological role of p53 inactivation in ERG fusion positive cancers. The very high number of prostate cancer samples included in the TMA used in this study allows for analysis of rare events such as p53 alterations with high statistical power.