bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel data processing and image co-registration algorithm for region-specific lipid profiling in colorectal cancer tissue using DESI imaging mass spectrometry.
Authors: Mirnezami Reza , Veselkov Kirill , Strittmatter Nicole , Kinross James M , Goldin Robert D , Speller Abigail , Jones Emrys A , Holmes Elaine , Abramov Tigran , Nicholson Jeremy K , Darzi Ara W , Takats Zoltan 
Published: March 2020

e14620 Background: Imaging mass spectrometry (iMS) is a promising technique for cancer biomarker discovery. Clinical translation of iMS requires advanced data treatment methods and efficient co-registration of histology and iMS imaging modalities. In this study desorption electrospray ionisation (DESI) iMS has been used to address four aims: 1. To develop a data processing workflow to address current limitations; 2. To design an interactive software platform for image co-registration; 3. To investigate region-specific lipid biochemistry in colorectal cancer (CRC) tissue using the strategy outlined in aims 1-2; 4.To introduce an automated tissue recognition system based on multivariate molecular ion patterns (MIPs). Methods: Fresh CRC tissue sections (n=49) were subjected to DESI-iMS using a Thermo Exactive mass spectrometer coupled with a DESI ion source. Mass spectra were collected in the range m/z = 200-1000. Sections were then H&E stained and scanned at high resolution. DESI-iMS data pre-processing involved peak detection, removal of noise/solvent related peaks and variance stabilising normalisation. An interactive image co-registration interface was developed using a feature-based image alignment algorithm for precise exploration of tissue region-specific biochemistry. A Recursive Maximum Margin Criterion (RMMC) algorithm was introduced for improved extraction of tissue specific MIPs. Results: CRC DESI-iMS profiles consisted mainly of complex lipids including phosphatidyl-inositols, phosphatidyl-serines, and phosphatidyl-ethanolamine plasmalogens. Different histological tissue regions showed characteristic lipid profiles. An automated tissue recognition system using multivariate MIPs derived by the proposed RMMC approach demonstrated highly accurate (classification accuracy >98%) identification of pixels according to tissue type (cancer, healthy mucosa, smooth muscle, fibrous tissue, stroma). Conclusions: This workflow permits accurate tissue-specific lipidomic characterisation of the CRC tumor microenvironment and permits accurate reconstruction of different tissue types based on MIPs.
Global clinical experience with adjuvant oxaliplatin/5-fluorouracil (5-FU)-based chemotherapy for colon cancer: Outcomes of the ACCElox registry.
Authors: Park Young Suk , Ji Jiafu , Zalcberg John Raymond , Elserafy Mostafa M. , Buzaid Antonio C. 
Published: March 2020

e14624 Background: The ACCElox registry assessed the therapeutic management of early stage colon cancer with oxaliplatin/5-FU-based regimen and duration of adjuvant chemotherapy in current clinical practice. Methods: Newly diagnosed patients (N=1,548) with stage II or III colon cancer, who had undergone complete resection of the primary tumor and treated with at least one dose of "oxaliplatin" were enrolled in this prospective observational study (Feb-2006–Jul-2008) and followed up till 36 months post-treatment. Results: 72.7% and 27.3% of the patients were diagnosed with stage III and stage II colon cancer, respectively. 1,152 (74.4%) patients completed the prescribed chemotherapy. The most frequent causes of discontinuation were refusal (9.0%), adverse events (AEs) (8.1%) or relapse/recurrence of disease (3.6%). Overall, 1,512 (97.6%) patients received at least one cycle of oxaliplatin regimen. Treatment delay occurred in 1,013 patients (67%), mainly attributed to AEs (40.9%) and personal inconvenience (35.5%). During the 3-year follow-up period disease relapse/recurrence occurred in 285 (18.4%) patients with similar rates in the three groups (FOLFOX: 18.1%, FLOX: 19%, and XELOX: 18.6%). Overall number of deaths reported at the end of 3- year study period was 72 (4.7%). Majority of AEs reported during treatment were of grade 1–2 and the most common ones were neutropenia (63.9%), thrombocytopenia (23.3%), diarrhea (9.7%), sensory neuropathy (4.5%) and infection (2.6%). Sensory neuropathy was the most frequent AEs reported at 6 and 12 months of post-treatment follow-up. Conclusions: A majority of the patients completed the prescribed oxaliplatin/5-FU regimen. No unexpected AEs were reported. Our results confirm the favorable benefit/risk profile of oxaliplatin/5-FU based regimens in clinical practice. [caption]Distribution and treatment outcomes.[caption] Clinical trial information: NCT01310972. [Table: see text]
Comorbidity and other predictors of survival in veterans with colorectal cancer (CRC) at different stages.
Authors: Zhong Fengming , Tang Ying Margie , Chang Victor Tsu-Shih , Patel Neal , Okoronkwo Nneoma Olivia , Gonzalez Melanie L. , Wang Trent P , Barnes Tanganyika , Paz-Querubin Emma R , Kasimis Basil 
Published: March 2020

e14625 Background: We analyzed comorbidity and other predictors of survival for patients (pts) with different stages of CRC. Methods: In an IRB-approved protocol, we reviewed the records of pts diagnosed with CRC at a VA medical center from 01/01/2003 to 12/31/2011 for demographics, stage, grade, ECOG performance status (PS), CEA, Hemoglobin (HGB), and Albumin (ALB) at diagnosis (dx). Comorbidity was assessed with the Charlson Comorbidity Index (CCI), the Cumulative Illness Rating Scales (CIRS), and the Kaplan-Feinstein Index (KFI). Statistical analyses were performed with SAS 9.2/Stata 11.0. We compared the pts with curative stage (0-III) vs late stage (IV) CRC. Results: There were 279 men. 156 pts (55.9%) were Caucasians, 106 pts (38%) African Americans, 15 pts (5.4%) Hispanics, and 2 pts (0.7%) Asians. The median (M) age at dx was 70 (45-90) years. 132 pts (47.3%) were deceased. 209 pts were curative stage at dx, 54 pts late stage and 16 pts unknown stage. Age and race were not different between the two stage groups. The late group had higher histological grades (P<0.001). In univariate analysis, age, stage, grade, ECOG PS, HGB, ALB, CCI, CIRS16, CIRS 17, CIRS 19, and KFI are significant predictors of survival for all stage pts. Significant predictors for curative stage pts are age, ECOG PS, HGB, CCI, CIRS16, CIRS17, and CIRS 18, and for late stage pts are grade, ECOG PS, ALB, and CCI. Significant factors by multivariate analysis are summarized in the table. Conclusions: These findings from this larger population confirm our earlier findings (ASCO 2012 e14125). Grade, stage, ECOG PS, and CIRS 19 (very severe comorbidity) are important independent survival predictors for veterans with CRC. Independent predictors for curative stage pts are ECOG PS and CIRS 16 (comorbidity severity summary score), and for late stage pts are ALB, CCI and CIRS 19. The late stage pts had higher grades. Further studies are needed to confirm this observation. Supported by NJCCR. [Table: see text]
Preoperative chemoradiotherapy (QT-RT) with capecitabine and oxaliplatin (CAPOX) in patients with locally advanced rectal cancer.
Authors: Sancho Aintzane , Marrodan Ines , Calvo Begoña , Muñoz Alberto , Mane Joan Manel , Carrera Sergio , Fuente Natalia , Azkona Eider , Arruti Mikel , Gutierrez Eddy Isabel , Ugalde Irene , Lopez-Vivanco Guillermo 
Published: March 2020

e14628 Background: Locally advanced rectal carcinoma is associated with high rate of abdomino-perineal amputation. We analyzed a cohort of patients (pts) diagnosed of locally advanced rectal cancer, treated with neoadjuvant QT-RT with CAPOX followed by four cycles of adjuvant CAPOX after surgery. Methods: Pts with locally advanced rectal cancer (T3-T4 and/or N+) were treated with oxaliplatin (50mg/m2 day 1, 8, 22 and 29) and capecitabine (1650mg/m2 on days 1 to 14 and 22 to 35) combined with pelvic radiotherapy (180cGy/day; 45Gy in 25 fractions). Surgery was scheduled 4 to 6 weeks after completion QT-RT. Four cycles of adjuvant XELOX were administered (capecitabine 2000mg/m2 on days 1 to 14) and oxaliplatin (130mg/m2 day 1) every 3 weeks. The main end points assessed were: rate of sphincter preservation, pathological complete response (pCR) rate, toxicity and feasibility of postoperative chemotherapy. Local staging was done with pelvic MRI and/or EUS. Results: From Sept 2005 to Nov 2012, 201 pts with locally advanced rectal cancer were included. Pts characteristics: M/F 135/66; ECOG 0/1/2: 48/149/4; median age 65 (28-81); upper/mid/distal rectum 29/105/67; stage cT3/N- 21, cT2-T3/N+ 140, cT4/N- 6, cT4/N+ 34. Full dose preoperative QT-RT was administered in 192 (95%). The main toxicities were diarrhea grade 2/3: 42/24 and neurotoxicity grade 1/2: 94/7. After treatment 198 pts underwent surgery. Sphincter preservation and R0 resections were achieved in 125 and 184 respectively. pCR was achieved in 35 pts (17.4%). 145 pts (72%) received all 4 cycles of adjuvant XELOX. Grade 3/4 toxicities included vomiting 3/0, diarrhea 7/0, skin-foot syndrome 2/0, mucositis 1/0, neurotoxicity 6/0, neutropenia 10/1 and thromopenia 6/1. Downstaging in T/N was achieved in 108/144 pts (53.7/71.6%) respectively. 3-year progression-free and overall survival were 75% and 83% respectively. No toxic deaths were reported. Conclusions: Combination QT-RT based in capecitabine and oxaliplatin is a well tolerated regimen and achieved encouring rates of pCR, R0 resection, sphincter preservation and tumor downstaging in patients with locally advanced rectal cancer.
Improving QOL and safety while reducing costs: Evidence-based adjuvant chemotherapy of colorectal cancer (CRC).
Authors: Shimp William S. , Kumar Akhil , Bobolts Laura Rose , Krook James Edward , Fishman Val , Davis Sharon , Anthony Carol , Walton Robert , Huff Dinah , Fishman Marc L. , Hrushesky William J. 
Published: March 2020

e14646 Background: The addition of oxaliplatin in adjuvant chemotherapy for stage II CRC and for elderly (≥ 70) patients with stage II or III CRC requires careful consideration. Most patients with stage II or III CRC receive oxaliplatin-based adjuvant regimens (Abrams. J Clin Oncol 2011). Mature results of the adjuvant MOSAIC and C-07 trials, however, failed to show improvement in OS or DFS among the elderly (≥ 70 years) and those with stage II CRC (Tournigand. J Clin Oncol 2012). Oxaliplatin causes neuropathy, increases the incidence and severity of febrile neutropenia, and adds substantial cost for both oxaliplatin and WBC growth factors. Methods: All chemotherapy requests submitted to Oncology Analytics for stage II and III CRC from 2009 through 2012 were analyzed. Utilization of oxaliplatin was retrospectively analyzed, with special attention to its use in those who were elderly (≥ 70 years), and for those of any age with stage II. Results: Our review showed a total of 242 adjuvant chemotherapy requests in stage II/III CRC. The majority of them, 57% (138/242), were elderly (≥ 70 years) with Stage II/III, and 24% (58/242) of any age had stage II. Thirty-four (14%) were both elderly and stage II. Overall, more than two thirds, 71% (171/242), received oxaliplatin containing regimens. More than two thirds of the elderly, regardless of stage, and more than half of all stage II patients, regardless of age, were treated with oxaliplatin containing regimens. Conclusions: The historical predominance of oxaliplatin use in the adjuvant setting, among patients over seventy years of age and/or those with stage II CRC, needs to be addressed as a priority. With mature data from the MOSAIC and C-07 trials, oncologists need to change prescribing behavior to provide less toxic therapies, thereby diminishing the incidence of neuropathy and reducing the risk of febrile neutropenia. The elimination of oxaliplatin in these subsets will also diminish costs for the Medicare population by a quarter billion dollars each year, without an adverse impact on outcome. [Table: see text]
Tolerability of raltitrexed when it is used in monotherapy and in combination with oxaliplatin (TOMOX) as advanced colorectal cancer treatment in normal clinical practice.
Authors: Constenla Manuel , Aparicio Jorge , Gomez M.Auxiliadora , Gravalos Castro Cristina , Lopez-Gomez Miriam , Manzano Jose Luis , Pineda Maria Dolores , Cano Juana Maria , Sevilla Isabel , Vieitez de Prado Jose Maria , Viudez Antonio , Lopez-Gomez Luis , Camara Juan Carlos , Lopez-Vivanco Guillermo , Aranda Fuensanta , Palomo-Jimenez Paloma Isabel , Barbon Ana , Feliu Batlle Jaime 
Published: March 2020

e14648 Background: Fluoropyrimidines (FP) based chemotherapy continue to be the cornerstone of advanced colorectal cancer (aCRC) treatment. However, FP cannot be appropriated for some patients (FP intolerance, DPD deficit, history of ischemic heart disease, etc). In these cases, Raltitrexed (R) in monotherapy or in combination with oxaliplatin (TOMOX) could be an effective alternative to FP. Methods: We assessed in an observational retrospective study the patient profile and the tolerability of R when it is used in monotherapy or in combination with oxaliplatin (TOMOX) as aCRC treatment in the normal clinical practice setting. Data from patients treated between 2010 and 2012 were collected from 15 Spanish hospitals. Reason for choosing R as aCRC treatment, patient and disease characteristics, previous treatment and toxicity were gathered. Results: The data from 144 patients treated with R (72) and TOMOX (72) were included in the analysis (64% male, median age 68 years, ECOG PS 0/1/2 in 18%/62%/19%). The main reasons to choose R were: similar efficacy and safety to other treatments (19%), convenience of the administration (18%), cardiovascular disease (17%), resistance to FP (14%), previous FP inacceptable toxicity (10%) and old age (11%). R was mainly used as third or successive treatment line (64%) while TOMOX was equally used in all treatment lines (37%, 28% and 35%). The mean number of cycles was 5 (1-15). The dose was reduced in 26% of the patients and the treatment administration was delayed in 53%. The creatinine clearance was only calculated in 20% of the cycles. The most common grade 3-4 toxicities were neutropenia (8%), anaemia (5%), nausea (2%), vomiting (1%), diarrhoea (7%) and hepatic toxicity (4%). There were 2 toxic deaths (1.4%). Conclusions: R and TOMOX represent a safe alternative for aCRC patients in which FP are not appropriated. Despite R good tolerance in normal clinical practice, it is a must to assess creatinine clearance before each cycle.
Mortality risk factors and survival of colon cancer patient.
Authors: Shi Runhua , Kodali Manga Devi , Wang Stephani Chang , Lavu Kalyana C , Liu Lihong , Shows Joseph Ryan , Mills Glenn Morris 
Published: March 2020

e14653 Background: It is estimated that 142,820 people will be diagnosed and 50,830 will die from colon cancer in U.S. in 2013. The known risk factors include age (>50 years old), personal history of colon polyp(s) and Inflammatory bowel disease, family history of colon cancer, hereditary syndromes, Black race, type II Diabetes Mellitus, obesity, physical inactivity, smoking and alcohol use. In order to improve colon cancer survivorship, current study explores factors that affect it. Methods: Data of 524,613 colon cancer patients between 1973 and 2009 was obtained from the Surveillance Epidemiology and End Results (SEER) program. Factors evaluated in this study were age at diagnosis, gender, race, annual household income, education, unemployment, and smoking. Clinical factors evaluated include SEER historic stage and treatments received. The definition of these factors was based on the SEER data dictionary. Kaplan-Meier method and log rank test was used to estimate and compare survivals. Cox regressions were used to identify risk factors that affect survival. Results: Characteristics of this half millions colon cancer patients were 51.3% of males, 84.4% of whites, and 70% of adjusted household income <$50,000. Primary site: Sigmoid Colon (30.84%), Cecum (22.7%), Ascending Colon (9.42%), and others (9.42%). Stage: Localized (37%), Regional (36.26%), Distant (20.01%), and Unstaged (6.63%). In multivariate analysis, adjusting for other factors, age (≤49 vs. 60-69, HR=0.57), female gender (HR=0.87), stage (localized vs. distant stage, HR= 0.15) and race (Black HR=1.38, vs. Asian) are significant factors in colon cancer survival. People living in areas with a high percentage of smokers have increased risk by 8%. People living in areas of higher unemployment have 6% increased risk. Household income and education level have relatively less effect on colon cancer survival (40-55k vs. 0-40k, HR=1.02). Conclusions: We conclude that in a large database, age, race, stage, smoking, and unemployment have significant impact on colon cancer survival. Other factors such as insurance status, detailed treatments, screening effect, individual life styles and etc. need further investigation.
Comparison of survival predictors in colorectal cancer (CRC) patients of different races.
Authors: Patel Neal , Okoronkwo Nneoma Olivia , Tang Ying Margie , Chang Victor Tsu-Shih , Kasimis Basil , Wang Trent P , Barnes Tanganyika , Cogswell Janet , Gonzalez Melanie L. , Einhorn Jan , Sullivan Maryann , Zhong Fengming 
Published: March 2020

e14661 Background: We studied comorbidity and other survival predictors for patients (pts) with CRC and compared the pts of different races. Methods: In an IRB-approved protocol, we reviewed the records of pts diagnosed with CRC at a VA medical center from 01/01/2003 to 12/31/2011 for demographics, stage, grade, ECOG performance status (PS), CEA, hemoglobin (HGB), and albumin (ALB) at diagnosis (dx). Comorbidity was assessed with the Charlson Comorbidity Index (CCI), the Cumulative Illness Rating Scales (CIRS), and the Kaplan-Feinstein Index (KFI). Statistical analyses were performed with SAS 9.2/Stata 11.0. We compared the pts by race groups Caucasian (C) vs African American (A). Results: There were 279 men. 156 pts (55.9%) were race C, 106 pts (38%) race A, 15 pts (5.4%) Hispanics, and 2 pts (0.7%) Asians. The median (M) age at dx was 70 (45-90) years. 132 pts (47.3%) were deceased. Age, grade, stage, ECOG PS, HGB, ALB, and CEA were similar between group A and C. In group A, M CCI is 4.2 (0.8-14), M CIRS 15 3.0 (0-5), M CIRS16 5 (0-13), M CIRS17 2 (0-6), M CIRS18 0 (0-1), M CIRS 19 0 (0-1), M KFI 2 (0-3). In group C, Median (M) CCI is 4.2 (0.4-19.6), M CIRS15 3.0 (0-6), M CIRS16 6 (0-13), M CIRS17 2 (0-13), M CIRS18 0 (0-1), M CIRS 19 0 (0-1) and M KFI 2 (0-3). By univariate analysis, for group A, grade, stage, ECOG PS, HGB, CCI, CIRS16, CIRS 19 and KFI are significant predictors. For group C, age, grade, stage, ECOG PS, HGB, ALB, and CIRS16 are significant predictors for survival. Summary for significant multivariate predictors are shown in the Table. Conclusions: This study from a larger population confirms our earlier findings (ASCO 2012 e14125). Grade, stage, ECOG PS, and CIRS 19 are independent survival predictors for veterans with CRC. Age, stage, ECOG PS, ALB and CIRS19 are independent predictors of survival for group C pts with CRC. Grade, stage, ECOG PS, and CIRS19 are predictors for group A pts with CRC. This variation may suggest biological difference between races. More studies are needed to confirm this. Supported by NJCCR. [Table: see text]
Visceral fat as a predictive marker of response to bevacizumab-based treatment in metastatic colorectal cancer.
Authors: Miyamoto Yuji , Sakamoto Yasuo , Watanabe Masayuki , Baba Hideo 
Published: March 2020

e14665 Background: A large amount of visceral adipose tissue might be correlated with high VEGF levels and with resistance to bevacizumab-based regimens in metastasic colorectal cancer (mCRC). The aim is to evaluate that abdominal obesity can be a predictive marker of response to bevacizumab-based therapy in mCRC. Methods: From January 2005 to December 2010, we performed a retrospective analysis of 74 consecutive patients with mCRC received bevacizumab-based first line treatment. Pretreatment CT was used to measure visceral fat volume (VFV), subcutaneous fat volume (SFV) an waist circumference (WC) in 74 patients with mCRC who received bevacizumab-based first-line treatment (bevacizumab group, n=37) or chemotherapy alone (chemotherapy group, n=37). Associations linkingVFV, SFV and WC to tumor response, progression free survival (PFS) and overall survival (OS) were evaluated. For all analyses, VFV, SFV and WC were dichotomized using the median as the cut-off point. Results: In the bevacizumab group, median follow-up lasted for 25 months (7-47). VFV, SFV and WC values were not associated with response or OS. PFS was shorter in patients with high VFV (12.8 vs 7.7 months; p=0.04). By multivariate analysis, high VFA was independently associated with PFS (HR=4.32, p=0.045). In the chemotherapy group, median follow-up lasted for 26 months (2-68). VFV, SFV and WC were not associated with response, PFS or OS. Conclusions: Visceral fat volume plays a role of predictive marker of PFS to bevacizumab-based therapy for Japanese patients with mCRC.
Predictive significance of VEGF and HIF-1α expression in metastatic colorectal cancer patients receiving chemotherapy combined with bevacizumab.
Authors: Berk Veli , Deniz Kemal , Karaca Halit , Inanc Mevlude , Bozkurt Oktay , Duran Ayse Ocak , Ozkan Metin 
Published: March 2020

e14672 Background: There is no suggested molecular indicator in identifying which patients will benefit from anti-angiogenic treatment in metastatic colorectal cancer. Over expression of vascular endothelial growth factor (VEGF) and Hypoxia Inducible Factor 1-alpha (HIF-1α) are associated with bad prognosis. In this study, VEGF and HIF-1α expression and their clinical significance are studied in tumor tissues of patients with colorectal cancer receiving treatment with bevacizumab. Methods: VEGF and HIF-1α were observed immunohistochemically in primary tumors of 53 patients. The expressions were separated by evaluating low and high of VEGF and HIF-1α expression. We evaluated whether expression of VEGF and HIF-1α can help to predict treatment response, progression free survival (PFS), and overall survival (OS). Results: Fifty-three patients were enrolled in the study. Median age was 55. VEGF was strongly expressed in 30 patients (57%) whilst low expression was observed in 23 of them (43%). When VEGF expression was evaluated in association with therapy response rates; the clinical benefit rate was 38% in the low expression group whereas it was 62% in high expression group. This difference was statistically significant (p=0.01). In the group with strong VEGF expression PFS was 10 months whereas it was 8 months in the low expression group (p=0.009). When evaluated for OS, 26 months versus 15 months was in favor of highly expressed VEGF group (p=0.03). Highly expressed HIF-1α was found in 29 patients (55%), on the other hand low expressed HIF-1α was detected in 24 (%45) patients. For clinical benefit rates, PFS and OS there was no difference between high and low expressed HIF-1α groups. Conclusions: It has been demonstrated that VEGF and HIF-1α expressions are associated with poor prognosis in several tumors, mainly colorectal carcinomas. With the better understanding of carciogenesis and angiogenesis at molecular level, especially VEGF and HIF-1α became target molecules of the therapy. According to results of our study, VEGF expression is a predictive factor in designating the metastatic colorectal cancer treatment.