bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient reported distress is predictive of survival in patients with gastrointestinal tumors.
Authors: Whitaker Dale Alan , Hintenlang Lauren L. , Jagadsh Niveditha , Strong Gerald , Buskirk Steven J. , Peterson Jennifer Layton , Tzou Katherine S. , Ko Stephen , Vallow Laura , May Byron C. , Habboush Jacob , Hollant Laeticia , Miller Robert Clell 
Published: March 2017

764 Background: Psychosocial distress screening and assessment in patients with gastrointestinal (GI) cancers has an established importance due to the distress experienced during and post treatment. GI cancer patients receiving radiotherapy (RT) for curative or palliative measures were reviewed in order to determine if there was a relationship between patient reported distress (PRD) and survival. Methods: Patients at our institution who receive external beam RT for GI cancers completed a 30 question PRD survey that also included a linear analog measure of overall distress, the National Comprehensive Cancer Network (NCCN) Distress Thermometer, which ranged from 1 (low overall distress) to 10 (high overall stress) at the start of and/or during treatment. Each question on the PRD questionnaire concentrated on a possible cause of distress. It allowed patients to rate distress levels for each question from 1 to 5 (1 being the least distressed and 5 being the most distressed), and also overall distress according. The reported clinical results of the PRD questionnaire were retrospectively reviewed in patients receiving RT for GI cancers from Jan 2012 to Aug 2015. Patients were considered distressed if their overall PRD score was 5 or greater (PRD+) or not distressed (PRD-) if their score was 4 or under. Overall survival between PRD+ and PRD- was compared using the Kaplan-Meier method. Results: PRD surveys were completed by 134 consecutive patients, 67 (50%) male and 67 (50%) female within 30 days of starting RT. The median age was 65 years (range 28 to 93). The top histological finding was adenocarcinoma, 90 patients (60%). 113 (84%) received chemotherapy and 64 (48%) underwent surgery. 102 (75%) treatments were curative and 32 (25%) were palliative. Overall NCCN distress thermometer results ranged from 0 to 10, with a median of 4. Median follow-up was 2.7 years. Distressed patients (PRD+) had inferior survival to those not distressed (PRD-) at 2 years, 52% vs. 72%, p<0.02. Conclusions: Patient reported distress is associated with an inferior survival in patients receiving radiotherapy for gastrointestinal tumors.
Effect of extended postoperative recovery on long-term oncological outcomes.
Authors: Poli Elizabeth , Sekigami Yurie , Rajeev Rahul , Gamblin T. Clark , Turaga Kiran 
Published: March 2017

765 Background: Curative cancer surgery remains the cornerstone of treatment of localized malignancies. Extended post operative recovery (eLOS) is associated with debility and immunosuppression. We hypothesized that eLOS is associated with worse long term oncological outcome. Methods: The NCDB participant user file from 2004-13 was utilized to identify patients with localized gastrointestinal malignancies undergoing curative cancer resections. Quartiles (Qx) of length of stay (LOS) were calculated based on histology and site specific indicators. Survival modeling was performed using cox-proportional hazards and conditional models were created. Alpha of 0.05 was set for statistical significance. Results: Of 1,616,215 patients in the cohort, 577,860 patients were included who met inclusion criteria. Majority of patients were ≥65 years (56%) with a predominance of colon cancer (70%). The median length of stay (LOS) varied from 5 days (partial hepatectomy) to 10 days (esophagectomy). After adjusting for age, gender, stage, and site of disease, increasing length of stay was significantly associated with worse oncological survival with a dose response effect (Q1 HR 1.0, Q2 1.12 (1.10-1.14) p<0.001, Q3 1.42 (1.41-1.44) p<0.001 and Q4 1.82(1.80-1.85), p<0.001). Conditional overall survival for patients who survived 3, 6 and 12 months after surgery, was worse with eLOS (p<0.001). Conclusions: Longer than expected length of stay after an index curative cancer operation leads to worse overall oncological outcomes. This effect persists even after excluding patients who suffer delayed post-operative mortality within 12 months after the operation. More research needs to be done to determine if this outcome is related to perioperative immunosuppression.
Rapid characterization of candidate loss of function genes in primary organoid culture.
Authors: Hart Daniel James , Salahudeen Ameen Abdulla , de la O Sean , Han Kyuho , Morgens David , Bassik Michael , Kuo Calvin Jay 
Published: March 2017

77 Background: Genome scale sequencing efforts have identified chromosomal deletions and non-synonymous mutations as putative drivers of gastro-intestinal cancer. There is a need to rapidly validate these drivers in robust models. The culture of primary, non-transformed tissues in vitro as three-dimensional organoids that accurately recapitulate organ structure and physiology serves as an ideal model for such validation, and many other applications in biology. Methods: Mouse wild type and p53 flox/flox upper digestive tract tissue containing epithelial and mesenchymal components were cultured in an air-liquid interface and subjected to adenovirus expressing either a functional control or Cre recombinase. Resultant organoids were passaged at confluency until dysplasia was evident in histology. A lentiviral shRNA (loss-of-function) screen was then conducted, where proliferative activity was measured with barcode reads from the pooled library. Results: p53-null organoids showed histology consistent with human gastrointestinal cancer. These organoids were also able to form small tumors when injected subcutaneously into immune-deficient mice. The pooled lentiviral shRNA screen functionally validated candidate drivers. Conclusions: Gastrointestinal organoids are a suitable model for the introduction of oncogenic mutations in a tractable and replicable format. In future work we will validate loss-of function and gain-of-function screens with CRISPRi/a libraries, and replicate these screens in human gastrointestinal organoids.
Left versus right: Does location matter for refractory metastatic colorectal cancer (mCRC) patients in phase I clinical trials?
Authors: Patel Sukeshi R. , Ketchum Norma S. , Michalek Joel , Gelfond Jonathan , Mahalingam Devalingam 
Published: March 2017

771 Background: Location of the primary tumor is prognostic and predictive of efficacy with VEGF-inhibitors (I) vs EGFR-I given first-line to mCRC patients (pts) (ASCO 2016). However, little is known regarding the effect of location on prognosis and prediction in heavily pretreated mCRC pts. We assessed the efficacy of VEGF-I and EGFR-I in regards to location of the primary tumor in pts with refractory mCRC enrolled in early phase studies. Methods: A historical cohort analysis of mCRC pts enrolled amongst 44 phase I trials at the IDD from 3/2004 - 9/2012. Median Progression free survival (mPFS) and overall survival (mOS) were estimated from Kaplan-Meier curves and groups were statistically compared with the log rank test. The magnitude of association between dichotomous factors and survival was estimated with the hazard ratio (HR). Results: 139 pts, median age 59 (33-81), KRAS mut 20 %, wt 31 %, unknown 49 %. ≥ 3 prior lines therapy 73.9 %; Prior EGFR-I 75.5% (100% of KRAS wt). Location: Right 20.9 %, Left 61.9 %, Transverse 4.3 %, Unknown 12.9 %. Phase I agents: VEGF I 19.4%, EGFR/Growth Factor I 9.3%. For survival analysis, transverse were included with right. Of 112 pts, mOS: Left (n = 80) 6.6 months (mo) vs Right (n = 32) 5.9 mo, p = 0.18. mPFS: Left (n = 86) 2.0 mo vs Right (n = 35) 2.0 mo, p = 0.76. Survival in regards to location or biologic agent (table). Conclusions: In phase 1 clinical trials, although location alone was not prognostic in heavily pretreated pts, left-sided mCRC had improved survival with EGFR-I. Despite progression on EGFR I, left-sided KRAS wild mCRC pts should be considered for phase 1 studies of agents targeting the growth factor pathways. [Table: see text]
Impact of RAS testing on treatment duration among patients with metastatic colorectal cancer (mCRC).
Authors: Bach Bruce A. , Christodoulopoulou Alexandra , Klink Andrew , Hechmati Guy , Mujumdar Urvi , Feinberg Bruce A. , Fakih Marwan 
Published: March 2017

773 Background: Current clinical guidelines recommend that all patients with mCRC have tumor tissue genotyped for RAS mutations. Tumor RAS testing enables the widest range of treatment options, with potential impact on patient outcomes. The aim of this study was to estimate the impact of RAS testing on the duration of treatment, across multiple lines of chemotherapy in mCRC. Methods: Adults with a diagnosis of mCRC (ICD-9 codes 153.x, 154.0x, or 154.1x and 197.x–198.x) were identified from a database of US public and private insurance claims (129 million covered lives) from 2012–2014. Time to treatment discontinuation, overall and by line of chemotherapy, was compared through univariate analysis between patients who were tested for RAS mutations (identified by CPT codes) to those who were not tested. Multivariate Cox proportional hazard regression model was used to estimate the risk of discontinuation attributable to prior RAS testing (i.e., hazard ratio [HR]), adjusting for patient characteristics. Results: We identified 4,527 mCRC patients (mean age at diagnosis, 61.2 years; 54% male), 39% (n = 1,787) of whom had a claim for RAS testing during the study period. Patients tested for RAS mutations stayed on treatment significantly longer in first-line (1LD), second-line (2LD), and overall treatment (OTD) vs those who were not tested for RAS mutations (1LD: median, 245 days [95% confidence interval–CI: 232–251] vs 196 days [95% CI: 189–205]; 2LD: median, 189 days [95% CI: 168–203] vs 147 days [95% CI: 133–161]; OTD: median, 903 days [95% CI: 815–1,040] vs 305 days [95% CI: 281–337]; all P < 0.01). Adjusting for patient characteristics, RAS testing significantly reduced the risk of discontinuation in 1LD, 2LD, and OTD (HRs: 0.83 [95% CI: 0.76–0.90], 0.80 [95% CI: 0.71–0.91], and 0.32 [95% CI: 0.27–0.37], respectively; all P< 0.01). Conclusions: These observational data show that RAS testing is associated with significantly greater time on treatment for mCRC patients compared to not testing, suggesting that patients under the care of physicians who decide to test for RAS mutations, regardless of test result, are on therapy for a longer period of time than untested patients.
Analysis of clinical and research implications of expanding next-generation sequencing (NGS) libraries in the treatment options of gastrointestinal cancers in a large cancer center.
Authors: Gonzalez Velez Miguel , Duma Narjust , Jaramillo Restrepo Valentina , Lopez-Zertuche Pablo , Kothadia Sejal , Mariotti Veronica , Parrondo Ricardo Daniel , Boseski Beth , Jennis Andrew , Gutierrez Martin 
Published: March 2017

774 Background: The use of next-generation sequencing (NGS) in clinical practice has increased the therapeutic options for many cancers. Multiple NGS assays are now commercially used. The genomic libraries used by these assays are continuously being expanded, resulting in increased detections of genomic alterations (GAs) leading to potential new treatments. The aim of this study was to identify the clinical and research implications of a database expansion in the detection of GAs in patients with gastrointestinal cancers (GIC). Methods: We retrospectively analyzed 83 consecutive patients with GIC that had NGS at the John Theurer Cancer Center between 01/2014 and 08/2016. GAs were identified using the FoundationOne assay (Foundation Medicine, Cambridge, MA). GAs, number of genomic-directed therapies and number of clinical trials were reviewed. Results: Period 1 (P1) comprised 01/2014-09/2014, period 2 (P2) comprised 10/2014-08/2016. The NGS assay interrogated 236 genes and introns of 19 genes during P1, and was expanded to 315 genes and introns of 28 genes during P2. The 21 samples analyzed during P1 harbored a total of 82 GAs with an average of 3.9 GAs/sample (range 1-7). The 62 samples analyzed during P2 harbored a total of 342 GAs with an average of 5.5 GAs/sample (range 1-20); representing an increase of 42% in GAs from P1 to P2. 41 GAs in 29 genes were detected in P2 that were not interrogated during P1. The average of genomic-directed therapies with potential clinical benefit increased from 1.8 during P1 vs 2.6 during P2 (44.4% increase in potential therapies). Based on new genomic findings, more clinical trials were made available during P2; an average of 8 vs 4 clinical trials (100% increase in available clinical trials). Conclusions: Periodical updates on NGS and the expansion of genomic libraries increase the detection of GAs, potential new genomic-directed therapies and available clinical trials. Continued expansions of NGS are needed to improve genomic characterization, and increase in the personalized therapeutic options for our patients with GIC.
Effect of subsequent chemotherapy on overall survival in first-line chemotherapy with targeted agents for patients with metastatic colorectal cancer: Systematic review and meta-analysis of randomized control trials.
Authors: Sakai Daisuke , Kudo Toshihiro , Kato Aya , Sueda Toshinori , Takahashi Hidekazu , Haraguchi Naotsugu , Nishimura Junichi , Hata Taishi , Matsuda Chu , Mizushima Tsunekazu , Doki Yuichiro , Mori Masaki , Satoh Taroh 
Published: March 2017

782 Background: One of recent standard first line chemotherapies for metastatic colorectal cancer is doublet of cytotoxic agents, fluorouracil and oxaliplatin or irinotecan, in combination with target agent, bevacizumab, or anti-EGFR antibody as cetuximab or panitumumab for KRAS or RAS wild type (WT). In this decade, nevertheless progression free survival (PFS) of clinical trials was little improved, overall survival (OS) had been increased. Methods: We analyzed data from 14 recently published phase III randomized clinical trials in mCRC to correlate the percentage of patients receiving subsequent chemotherapy with the reported OS. Results: Median PFS and OS were 10.3 and 25.0 months, respectively. In all comer trials, median OS is significantly correlated with the percentage of patients who received subsequent chemotherapy after first line chemotherapy of their disease [regression coefficient (R2) = 0.85 p = 0.0018]. In trials with KRAS WT, a correlation between OS and the rate of subsequent therapy was modest [r2 = 0.605, p = 0.0637]. Median PFS and RR were not correlated with median OS. Conclusions: Our results support the strategy of making salvage chemotherapy available to all patients with advanced CRC to maximize OS. In addition, our findings suggest that, with the availability of effective salvage options, PFS might no longer be regarded as the appropriate surrogate end point of OS by which to assess the efficacy of a palliative first-line treatment in CRC.
Self-reported adherence to regorafenib for metastatic colorectal cancer: A retrospective cohort study.
Authors: Kawakami Kazuyoshi , Suenaga Mitsukuni , Soejima Azusa , Sugita Kazuo , Yokokawa Takashi , Suzuki Kenichi , Inoue Ayaka , Machida Yohiaki , Wakatsuki Takeru , Yamaguchi Kensei , Hama Toshihiro 
Published: March 2017

783 Background: Regorafenib is an oral multikinase inhibitor for metastatic colorectal cancer (mCRC) and it is frequently involved in various adverse events. The clinical factors affecting adherence to regorafenib remain unclear. The aim of this study is to evaluate adherence to regorafenib in patients with mCRC and to identify candidate factors which might have influence on adherence to regorafenib. Methods: We evaluated 106 consecutively enrolled patients with mCRC who received regorafenib between May 18, 2013 and March 2, 2015 at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. Adherence to regorafenib was checked by pharmacists using a self-reported treatment diary for patients at a pharmaceutical outpatient clinic. The adherence rate was defined as the number of actual intakes per 21 intakes scheduled in each cycle. We retrospectively surveyed median relative dose intensities of regorafenib and the factors deteriorating adherence across three cycles. Univariate analyses were then performed using patient socio-demographic factors and clinical factor. Multivariate analysis was performed using logistic regression. Significance levels for uni- and multivariate analyses were p < 0.2 and p< 0.05, respectively. Results: A total of 81 patients were evaluated in the study analysis. Adherence rates were 64.4% in the first cycle of regorafenib treatment, 77.4% in the second cycle, and 83.8% in the third cycle. The median relative dose intensity was 57.6%. The most common reasons for non-adherence were hand-foot skin reaction (34.3%, 331 instances), and liver dysfunction (15.3%, 148 instances). In multivariate analysis, increased non-adherence to regorafenib was significantly associated with gender (female) [odds ratio (OR) = 0.20; 95% confidence interval (CI): 0.06-0.68, p = 0.01] and adverse events ( ≥ Grade 3) [OR = 3.16; 95% CI: 1.00-9.97, p= 0.04) in the first cycle.] Conclusions: The high frequency of treatment-related hand-foot skin reaction and liver dysfunction is the main factor affecting adherence to regorafenib. Intensive supportive care in the management of these symptoms could assist adequate adherence to regorafenib.
Adjuvant treatment in extreme elderly patients with colorectal cancer.
Authors: Llopis Cuquerella Marta , Ors Castaño Maria del Carmen , Ballester Espinosa María , Magdaleno Cremades Alejandra , Boix Aracil Vicente , Ramirez Belloch María del Rocío , Morales Giménez Roberto , Gómez González Lucía , Asensio Martinez Elena , Navalón Coronado Juan Carlos , Navarro Rodriguez Jose Manuel , Soliveres Soliveres Edelmira , Morcillo Ródenas Miguel Ángel , Gallego Plazas Javier 
Published: March 2017

784 Background: Surgical and adjuvant treatment in extreme elderly ( > 80 years) patients with localized colorectal cancer is an unresolved issue. Owing to the lack of available neither clinical practice nor investigational data in this field we present our experience in this scenario. Methods: We retrospectively reviewed data regarding surgical and complementary treatment for colorectal cancer patients aged more than 80 consecutively attended by General Surgery Department in Vega Baja Hospital between 2008 and 2013. Results: A total number of 115 colorectal cancer patients were registered. 95 patients diagnosed of localized disease were selected for analysis. Colon vs rectal cancer ratio was 4:1. Median age was 83.6 years (80-94). Male sex was predominant (60 patients, 63.2%). Emergency surgery was performed in 15 patients (15.8%). Complementary treatment to surgery was advised, according to international guidelines, in 53 patients (55.8%). 10 patients (18.9%) with an advise of adjuvant treatment finally received it. More patients with rectal cancer received recommended treatment (41.7% rectal vs 12.2% colon cancer). Patients with stage III disease were more frequently finally treated according to guidelines (22.2 % stage III vs 11.8% stage II). More patients with stage II rectal cancer were advised and received treatment (recommendation: 66.7% rectal vs 36.1% colon cancer; administration: 25% rectal vs 7.7% colon cancer). Treatment was also more frequently administered to stage III rectal cancer (50% rectal vs 14.3% rectal cancer) (Table). Conclusions: Our experience in localized colorectal cancer in extreme elderly patients ( > 80 years) showed that, although advised according to guidelines, most of them did not receive adjuvant treatment to surgery. Complementary treatment administration was more common in rectal cancer patients and with more advanced disease. [Table: see text]
Prognostic impact of tumor (T) and lymph node (N) status in metastatic colon cancer (MCC): A validation study using the National Cancer Database (NCDB).
Authors: Mukkamalla Shiva Kumar Reddy , Somasundar Ponnandai Sadasivan , Rathore Bharti 
Published: March 2017

786 Background: T and N status are not routinely utilized in prognosis of MCC. We had previously demonstrated that T and N serve as independent predictors for overall survival (OS) in MCC using SEER [Ann Oncol (2014) 25 (suppl 4): iv172-iv173]. The current study is undertaken to validate our findings using the NCDB. Methods: The NCDB was queried for patients diagnosed with MCC from 2004-2008 with survival information up to 2013. Pearson Chi-square test, Kaplan Meier survival curves and Cox proportional hazards model were used for statistical analysis. Results: A cohort of 5,788 patients was identified for analysis. Frequencies of T1, T2, T3 and T4 among the study population were 6.6%, 4.2%, 52.6% and 36.6% respectively, whereas N0, N1 and N2 were noted in 28.5%, 29.9% and 41.6% respectively. 5-year OS worsened with advancing T and N status, with the exception of T1 disease (Table). T1 disease was associated with poor prognosis compared to T2 and T3, but showed better survival outcome than T4 (p < 0.05). Both T and N were identified as independent predictors of OS regardless of age, gender, race, comorbidity index, insurance status, income level, tumor sidedness, tumor grade, surgery, chemotherapy and academic level of treating institution. In multivariate analysis, we found left sided tumors to have better survival outcome compared to right (HR 0.85; p < 0.0001). Conclusions: Similar to our previous findings, in MCC patients, a T1 status portends poor prognosis compared to T2 or T3 disease. It is possible that an overrepresentation of tumors, with a distinct biological subtype characterized by a tendency for early dissemination in T1 disease could be associated with poor outcomes observed in this patient subgroup. In future, we plan to validate this finding through T1 subgroup analysis. Our study also demonstrates poor OS in right sided tumors compared to left sided tumors, similar to prior studies by Schrag et al and Venook et al. [Table: see text]