bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-specific prognostic factors in patients treated surgically for pulmonary metastases of colorectal cancer: A multi-institutional cumulative follow-up study.
Authors: Nakao Sayumi , Itabashi Michio , Ubukata Mamiko , Bamba Yoshiko , Hirosawa Tomoichiro , Ogawa Shimpei , Kameoka Shingo , Sugihara Kenichi 
Published: February 2017

773 Background: The aim of this study was to investigate the age-specific prognostic factors for overall survival (OS) and disease-free interval (DFI) after pulmonary metastasectomy for colorectal cancer (CRC). Methods: We performed a retrospective analysis of 1,179 patients who underwent lung resection for colorectal metastases from 2001 to 2012 in 109 affiliated institutions of the Japanese Society for Cancer of the Colon and Rectum study group. The patients were divided into three groups by the age at pulmonary resection: Group A (GA) comprised of 396 patients who underwent lung resection under the age of 60 years old; Group B (GB) comprised of 604 patients who underwent lung resection between the ages of 61 and 74 years old; Group C (GC) comprised of 179 patients who underwent lung resection over the age of 75 years old. We used the Cox proportional hazard regression to identify independent prognostic factors for OS and DFI. Results: Median OS times after pulmonary resection were 45 months, 43 months, and 43 months for GA, GB, and GC, respectively. Two-year and 5-year overall survival rates were 73% and 54% for GA, 77% and 63% for GB, and 82% and 68% for GC, respectively. The independent unfavorable prognostic factors were recurrence after pulmonary resection (p<0.0001) in GA, detection of liver metastases before lung resection (p=0.0126), a high level of carcinoembryonic antigen (p=0.0003), and recurrence after pulmonary resection (p<0.0001) in GB, and recurrence after pulmonary resection (p<0.0001) in GC. Median DFI times were 11 months in all groups. The independent unfavorable prognostic factor was a removal of mediastinal lymph node (p=0.0335) in GB. Conclusions: Elder patients (GC) showed nearly the same OS rate compared with non-elder patients (GB), while younger patients (GA) showed poor OS rate. Recurrence after pulmonary resection revealed to be a poor prognostic factor in all groups.
Colorectal cancer mortality among Cuban and non-Cuban Hispanics.
Authors: Sussman Daniel A. , Tannenbaum Stacey L. , McClure Laura A. , Hernandez Monique N. , Zheng D. Diane , Koru-Sengul Tulay , Carrasquillo Olveen , Lee David J. 
Published: February 2017

775 Background: We examined all-cause mortality of Floridian colorectal cancer (CRC) patients among Hispanics of Cuban and non-Cuban origin, non-Hispanic Whites (NHWs) and non-Hispanic Blacks (NHBs). We hypothesized that Cuban Hispanics would have a higher mortality risk relative to other Hispanics in Florida with CRC. Methods: We obtained data from the Florida Cancer Data System for all incident CRC cases (2007-2011) among Floridians 18+ years and linked these files with data from Florida’s Agency for Health Care Administration and the 2006-2010 American Community Survey (n=46,579). Race/ethnic groups were Cuban, non-Cuban Hispanic, NHW, and NHB. Log-rank tests were performed among race/ethnic groups with multivariable Cox proportional hazard regression models for mortality adjusting for demographic and clinical factors to produce adjusted hazard ratios (HR). Results: Cubans’ mortality were not significantly different from NHWs (p=0.8254) or NHBs (p=0.3047) but significantly different from non-Cuban Hispanics (p=0.0006). Adjusting for all covariates and compared with highest SES within each race/ethnicity, residing in lower SES neighborhoods was associated with increased mortality risk for NHWs (HR=1.19; 95%CI=1.12-1.27) and NHBs (1.33; 1.13-1.57) but not for Hispanics. Among Hispanics, Cubans with proximal CRC had a 42% higher mortality risk than those with distal disease (1.42; 1.11-1.82); however, tumor location was not predictive of mortality for other racial/ethnic groups. Single or widowed Cuban Hispanics had higher mortality risk compared to those who were married (1.42; 1.07-1.88 for both comparisons) but this was not true for non-Cuban Hispanics. Conclusions: Cuban Hispanics are a distinct and understudied population group who should not be aggregated into a general category of Hispanic with respect to CRC mortality studies. Further research to understand the Cuban Hispanic differences in CRC mortality risk is needed to reduce the burden of disease, especially in the ever growing Hispanic population.
Triplet chemotherapy (TC) with FOLFIRINOX regimen in metastatic colorectal cancer (mCRC): Experience of two French centres.
Authors: Samalin Emmanuelle , De La Fouchardiere Christelle , Thézenas Simon , Sarabi Matthieu , Assenat Eric , Portales Fabienne , Carrere Sebastien , Rivoire Michel , Rouanet Philippe , Bleuse Jean-Pierre , Quenet François , Ychou Marc 
Published: February 2017

776 Background: TC is a treatment option for mCRC to improve the tumour response rate in selected patients (pts) and the conversion rate of initially nonresectable liver metastases. The aim of this study was to evaluate the impact and feasibility of FOLFIRINOX regimen in mCRC pts. Methods: We selected all mCRC pts from the ICM and CLB French centres with unresectable disease treated from October 2000 to May 2012 with FOLFIRINOX alone or combined with bevacizumab or cetuximab. Clinical data were collected in a mCRC-specific data base and analysed. Results: 159 pts (52% of men), median age 58 yrs (range: 24-76) were treated with FOLFIRINOX (D1 oxaliplatin 85 mg/m² IV over 2H, then irinotecan 180 mg/m² IV over 90 min and elvorin 200 mg/m², then 5-fluorouracile 200 mg/m² and 2,400 mg/m² IV over 46H, D1=D15) alone (68%) or combined with cetuximab (24%) or bevacizumab (8%) as first–line treatment (88%). Primary tumour was located in colon (77%) or rectum (23%), and 134 pts (84%) presented with synchronous metastases: liver (96%), lung (46%), peritoneum (11%) and nodes (20%). Median number of courses was 8 (range: 1-26). There was 1 toxic death. Grade 3-4 toxicities were as follows: diarrhoea (23%), neuropathy (24%), cutaneous (9%), neutropenia (21%), febrile neutropenia (1%), thrombopenia (4%). Objective response rate according to RECIST V1.0 was 72% [95% CI: 65-79] including 12 pts with complete response. The primary tumour was resected in 127 pts (79%) and 19% had KRAS mutated tumour. Among the 105 pts (66%) with initially non-resectable liver-limited disease (LLD), 59 pts (56%) were eligible for secondary resection and a R0 resection rate was achieved for 44 pts. Median overall survival was 49 months [95% CI: 37-62] and 72 months [95% CI: 48-84] in resected LLD population. Conclusions: These results confirm the feasibility of FOLFIRINOX regimen with or without targeted therapies and its efficacy in LLD selected mCRC population.
Gastrointestinal organoid cultures for functional evaluation of oncogenic loci.
Authors: Salahudeen Ameen Abdulla , Li Xingnan , Cantrell Michael , Kuo Calvin Jay 
Published: February 2017

85 Background: Novel in vitro methods surpassing limitations of current gastrointestinal cancer models such as gastric and esophagus cancer are required to functionally validate putative oncogenic loci discovered by genome sequencing efforts. The in vitro culture of primary, non-transformed tissues as three-dimensional organoids that accurately recapitulate organ structure and physiology has diverse applications including cancer biology. Methods: Mouse wild type, or p53flox/flox in tandem with lox-stop-lox KRASG12D upper digestive tract tissue containing epithelial and mesenchymal components were cultured in an air-liquid-interface and subjected to adenovirus expressing either immunoglobulin Fc (control) or GFP tagged Cre recombinase. Results: 3-dimensional organoids were generated with histological adherence to normal tissue architecture including that seen in esophagus and were able to be maintained in long term culture. Organoids exposed to GFP tagged Cre adenovirus demonstrated green fluorescence not seen in organoids exposed to control virus. Conditional allele organoids that were exposed to Cre adenovirus demonstrated increased rate of growth compared to controls. Histology of these rapidly growing organoids demonstrated cellular features consistent with dysplasia. Conclusions: 3-dimensional organoids can be generated from upper digestive tract tissues, can undergo adenoviral mediated transfection to achieve oncogenic gene expression or inactivation resulting in dysplastic morphology. 3-dimensional organoids are therefore an attractive model to study or identify candidate oncogenic loci identified by recent genomic sequencing studies.
Evolution in the treatment of esophageal disease at a single institution: 2004-2013.
Authors: Pham David V , Dolan James P. , Diggs Brian S. , Gilbert Erin W. , Sheppard Brett C. , Tieu Brandon , Schipper Paul , Giraud Fernando M , Thomas Charles R. , Hunter John G. 
Published: February 2017

96 Background: The aim of this study was to analyze the evolution in the surgical management of esophageal disease at an academic medical center during the last decade. Methods: We reviewed a retrospective cohort of patients who underwent esophagectomy between 2004 and 2013 for benign and malignant esophageal disease. Patient, institutional and postoperative variables were abstracted and reviewed across the study period. Results: 317 patients were analyzed. The median age was 63.5 years and 80% were male. Malignancy accounted for 88% of esophagectomy patients in 2004 and 97% in 2013. Operations for high grade dysplasia (HGD) decreased 75% in the same period (p=0.008). In 2004, an Ivor Lewis esophagectomy was the most common surgical technique but the 3-Field technique has become the operation of choice in 2013 (54% vs.71%, p<0.001). Likewise, a laparoscopic approach was used in 19% of cases in 2004 and 100% of cases in 2013 (p<0.001). Median lymph node harvest increased from 7 to 18 nodes (p=0.001). Atrial fibrillation was the most common perioperative complication (24%) and anastomotic leaks ranged between 3 to 14% (p=0.18), occurring in 3% of patients in 2013. Hospital stay decreased from 15 to 8 days over the study period (p=0.001). In 2013, 89% of patients were discharge to home compared to 73% in 2004 (p=0.04). The average mortality rate for our cohort was 3.5%. Conclusions: Over the last decade, our treatment of esophageal disease has evolved from a predominant open Ivor Lewis to a laparoscopic 3-Field approach. Operations for malignancy have also increased dramatically. Postoperative complications and mortality has been consistently low during the latter years of the study.
Discovery and validation of a 30-gene expression signature to identify prostate cancer patients who are candidates for active surveillance.
Authors: Gerke Travis , Tyekucheva Svitlana , Penney Kathryn , Sweeney Christopher , Lis Rosina , Sesso Howard D. , Nuttall Elizabeth , Loda Massimo , Stampfer Meir J. , Parmigiani Giovanni , Mucci Lorelei A. 
Published: February 2017

10 Background: Considerable attention has been devoted to the search for biomarkers of aggressive prostate cancer. While many promising markers have been proposed, it is often unclear whether their ability to risk classify is adequate to reduce overtreatment of indolent cancers. We present and validate a gene expression signature that is highly specific for indolent disease and that, when combined with Gleason, improves upon the prognostic power of Gleason alone. Methods: A 30-gene signature of indolent disease was derived from a case-control sample of men (n=254) from the Health Professionals Follow-Up Study (HPFS) who were followed prospectively from cancer diagnosis for a median of 13.7 years. Cases were defined as men with prostate cancer who experienced a metastatic event or died of cancer during follow-up, while indolent controls survived at least 8 years without metastases. Whole-transcriptome gene expression was quantified from archival formalin-fixed, paraffin-embedded (FFPE) tumor tissue specimens acquired at prostatectomy. Genes were selected by a novel analytic strategy that maximizes a partial area under the curve (pAUC) to accurately identify indolent tumors. We validated the signature in two independent cohorts: the Physicians’ Health Study (PHS; n=150) and a Swedish Watchful Waiting cohort (WW; n=253) with respective median follow-up times of 14.4 and 9.0 years. Results: When compared to a model with Gleason alone, application of the signature to both validation data sets significantly improved prognostic accuracy as measured by pAUC (p=0.003 in PHS and p<0.001 in WW). Performance was particularly strong among men diagnosed with Gleason 7, where unit standard deviation increases in the signature score were associated with odds ratios of indolence of 5.24 (95% CI 2.21-15.75; p<0.001) and 2.37 (95% CI 1.45-4.19; p=0.001) in the PHS and WW cohorts, respectively. Conclusions: We present a signature of indolent prostate cancer that adds prognostic information beyond Gleason and has the potential to guide men to active surveillance and avoid overtreatment. Validation across both treated and untreated cohorts supports the discovery of a robust signature.
Familial risk and heritability of genitourinary cancers in the Nordic Twin Cohorts.
Authors: Mucci Lorelei A. , Hjelmborg Jacob , Penney Kathryn , Skytthe Axel , Harris Jennifer , Adami Hans-Olov , Kaprio Jaakko 
Published: February 2017

11 Background: Twin studies estimate familial risk and heritability by leveraging the unique genetic relatedness of twins. We analyzed data from the Nordic Twin Study to investigate the genetic underpinnings of risk of genitourinary cancers. Methods: The cohort included 202,868 monozygotic (MZ) and same-sex dizygotic (DZ) twins from nationwide registries with follow-up via cancer registries. We examined cancers of the prostate, bladder, kidney and testes, and estimated familial risk, risk of a specific cancer in a twin, given that his co-twin was diagnosed with the same cancer, and heritability, the proportion of variation in cancer risk due to genetic differences. Statistical models used time-to-event analyses and accounted for censoring and competing risk of death. Results: During 32 years of follow-up, 5,041 cases of genitourinary cancer were diagnosed. The cumulative incidences in the cohort overall were 10.5% for prostate, 2.2% for bladder, 0.8% for kidney and 0.5% for testes. The strongest familial effects were found for testicular cancer. The familial risks of testicular cancer were 6% for DZ and 14% for MZ twins, i.e. a 12-fold and 28-fold higher risk for DZ and MZ twins, respectively, when their twin was also diagnosed with testicular cancer. Familial risk was also elevated for prostate, bladder, and kidney cancer and showed higher estimates among MZ than DZ twins. Statistically significant estimates of heritability were observed for prostate (57%) and kidney (38%) cancer, while testicular cancer showed evidence of both genetic (37%) and shared environmental (24%) effects. Conclusions: Familial risk estimates provide evidence of significant excess risks for individuals whose siblings develop genitourinary cancers. The higher concordance in MZ vs. DZ twins translated to strong heritability estimates for these malignancies. Results from this study have the potential to be directly translated to clinical practice and genetic counseling, and provide a context for the findings from genome wide association studies.
Primary focal cryosurgery of the prostate: Long-term clinical and biochemical outcomes in a large cohort at a tertiary referral center.
Authors: Pak Jamie Sungmin , Cheetham Philippa J. , Katz Aaron , Wenske Sven 
Published: February 2017

114 Background: Modern primary focal cryosurgery (PFC) has emerged as a primary therapy option for localized and minimal low-risk prostate cancer (PCa), achieving good local cancer control and survival outcome. The aim of this analysis was to report on the experience of PFC in our tertiary referral center in the management of localized PCa. Methods: We identified a consecutive series of patients that underwent PFC for localized PCa at our institution between 8/2000 and 1/2014. Demographics, PSA levels and Gleason scores before primary treatment and at time of recurrence were assessed; BDFS, OS, and DSS were assessed. BCR was defined by the Phoenix (PD) and Stuttgart Definitions (SD). Results: A total of 126 patients were included in the analysis, with a median follow-up of 40.3 (0.8-116, IQR 41) months. Median age was 73.5 (range 45-92, IQR 9) years. Median initial serum PSA level was 6.0 (1-44.5, IQR 3) ng/ml. Median primary and secondary Gleason score on initial biopsy was 3 (3-5, IQR 1) with a median sum of 6 (6-10, 1), and 15% (2-95%, IQR 0) of biopsy tissue involved with cancer. Median number of biopsy cores was 12 (2-32), with a median of 1 (1-12, IQR 1) core affected by cancer. Median PSA nadir post-treatment was 1.3 (0.1-13.1, IQR 2) ng/ml. According to PD and SD, 24 and 37 patients had BCR after a median of 14.9 (3.4-91.3, IQR 17) and 13.0 (2.9-90.3, IQR 11) months. Overall 4-year-BDFS was 83% and 73% by PD and SD, respectively. 5-year OS and DSS was 95%, and 99.2%. Of patients that met BCR criteria, almost 25% were proven to be negative on biopsy, confirming over-estimation of failures. Patients that recurred had significantly higher initial median PSA levels (8.5 vs. 5.8 ng/ml; p<0.01) and PSA-nadir (2.1 vs. 1.0 ng/ml; p<0.05). Conclusions: Our analysis confirms PFC being a good option with low rate of morbidities for patients with localized PCa, with excellent BDFS and DSS at a long follow-up of 40 months. Controversy exists regarding criteria of BCR-definitions after focal therapies. More stringent definitions, such as the SD, especially in a focal cryosurgery setting, significantly over-estimate failure rates, and prostate biopsy seems to be the only reliable means to assess for recurrence at this point.
Grade 3 or higher morbidity requiring urologic surgical management following curative-intent radiotherapy of localized prostate cancer: Patient characteristics.
Authors: Thorpe Cameron S. , Myers Jeremy B. , Shrieve Dennis C. , Tward Jonathan D. 
Published: February 2017

116 Background: Although there are prospective data reporting the incidence of grade 3 morbidity after treatment of prostate cancer (PCA), little has been reported on the specific morbidities, latency period and surgical management of these patients. We retrospectively evaluated the characteristics of patients treated for grade 3 or higher complications at the University of Utah. Methods: We identified patients with PCA from our institutional database who were treated with definitive or postoperative radiation between the years 1995 and 2012 with at least 1 CTCAE defined Grade 3 or higher adverse event (AE). We evaluated the details of surgery and/or radiation, time course to development of AE’s, and procedures performed to manage the AE’s. Descriptive statistics were performed. GI toxicities were not evaluated. Results: There were 208 Grade 3 events reported in 44 patients. Five had a single event, 8 had 2 events, and 31 patients had 3 or more. Following radiotherapy, 21 patients initially presented with a grade 3 toxicity, whereas 12 presented with a grade 1 and 11 presented with a grade 2 that progressed to grade 3. One subject had a grade 4 toxicity. There were 9 subjects who reported baseline grade 1 to 3 toxicity prior to curative-intent treatment. The most common Grade 3 events were: obstruction (100 events), incontinence (40 events) and fistula (21 events). Fourteen patients had surgery and EBRT, and at least 16 patients had HDR brachytherapy. The average latency period to the first grade 3 event was 76.8 months (range 0 to 195 months). Between 2005 and 2010 an average of 531 and 92 patients with PCA were treated with radiation in the state of Utah (SEER) and the University of Utah annually, respectively. Conclusions: Grade 3 or higher urologic morbidity is uncommon following prostate cancer radiation treatment. Combinations of radiation therapies and HDR brachytherapy appear to increase the risk of an adverse event. Outcome studies reporting late toxicity with median follow up of less than 5 years may significantly under-report the incidence.
Young age to predict for transient elevation in PSA after definitive stereotactic body radiation therapy for prostate cancer.
Authors: Blacksburg Seth , Katz Aaron , Witten Matthew R. , Clancey Owen , Haas Jonathan A. 
Published: February 2017

118 Background: Stereotactic Body Radiation Therapy (SBRT) is a standard therapeutic option for men with prostate adenocarcinoma. There is a small body of literature characterizing a PSA bump after treatment with SBRT. Despite this, there is a paucity of data addressing rates of transient PSA increase immediately after SBRT treatment and what factors portend for this rare occurrence. This study reports outcomes on initial PSA after SBRT therapy for men who have received definitive SBRT for prostate cancer. Methods: Between May 2006 and February 2014, 921 patients with prostate cancer were treated with SBRT delivered via Cyberknife therapy. The mean age was 67 years old. 68.5% of patients were Caucasian, 17.4% African American, and 14.1% were another ethnicity. Patients were divided into prognostic risk groups with 44.7%, 43.5%, and 11.1% of patients falling in the low, intermediate, and high risk stratifications. Gleason scores were < 6 in 44.4%, 7 in 41.3%, and 8-10 in 14.2%. 37 patients also received supplemental external beam radiation (median dose 4500cGy) and 8.9% of patients received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. Pre-treatment PSA was 0.8 – 205 ng/ml (median 6.1). Results: At 3 months’ follow-up, 2.8% of patients had a PSA elevated above their baseline value. 27.8% of patients age ≤50 (p<.0001) and 8.4% of patients age ≤60 (p=.001) experienced an increased in baseline PSA. African Americans were more likely to experience a transient increase in PSA over Caucasians (7.8% vs. 3.0%, p=.06). Patients treated with fewer beams were also more likely have a temporary rise in PSA (p=.056). Gleason Score, Risk grouping, prostate volume, ADT, and EBRT did not predict for rise on Pearson Chi-Square analysis. On multivariate analysis, only age ≤50 (p<.0001) portended for increased PSA at 3 months’ time. Conclusions: This represents the largest series evaluating elevation of PSA after definitive SBRT for prostate cancer. Temporary rise in baseline PSA after SBRT is rare. Despite that, a significant cohort of younger patients can experience transient elevation. Patient age ≤50 was found to be the only predictor of this otherwise rare occurrence.