bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of capecitabine +/- erlotinib in advanced colorectal cancer, with retrospective KRAS and primary tumor site analysis.
Authors: Breadner Daniel Adam , Welch Stephen , Soulieres Denis , Sanatani Michael Susmoy , Klimo Paul , MacKenzie Mary J. , Whiston Frances , Stitt Larry , O'Connell Anne , Vincent Mark David 
Published: March 2017

781 Background: Palliative capecitabine (X) monotherapy for advanced colorectal colorectal cancer (aCRC) is generally well tolerated by elderly or frail pts. Epidermal growth factor receptor (EGFR) monoclonal antibodies improve efficacy when added to combination chemotherapy for mCRC. Erlotinib (E), an oral EGFR tyrosine kinase inhibitor (TKI) may add benefit when added to X. We conducted a randomized phase II trial to investigate the novel “all-oral” combination of X and E in aCRC. Methods: Pts with untreated aCRC who were either deemed unfit for, or chose against, combination chemotherapy were randomized to X (1000 mg/m2 PO BID x 14 days) alone or in combination with E (150 mg PO OD) on a 3-week schedule. Primary endpoint was time to disease progression (TTP); secondary endpoints included: objective response rate (ORR), overall survival (OS), and safety. Tumours were designated as left-sided if there were distal to the transverse colon. KRAS status was retrospectively analyzed for 72 of 82 pts. Results: From 2004 to 2008, 82 pts were randomized to X alone (40 pts) or XE (42 pts). TTP was not different between X and XE (7.9 m vs. 9.2 m; p = 0.890), however, KRAS subgroup analysis revealed pts with KRAS mutations did significantly worse when treated with XE compared to X alone (1.9m vs 7.4m; HR = 2.63; P = 0.038). Pts with KRAS wild-type (WT) treated with XE had an improved TTP compared to those treated with X (11.7m vs. 8.4m, HR = 0.73; Wilcoxon P = 0.061). KRAS-WT pts treated with XE with left-sided disease had an improved OS compared to pts with right-sided disease (16m vs. 12.1m, not significant). KRAS-WT pts with left-sided primaries treated with XE had a non-significant improvement in TTP compared to pts treated with X alone (11.7m vs 8.4m). XE was well tolerated but had significantly higher rates of diarrhea and acneform skin rash. Conclusions: The addition of E to X is generally well tolerated but associated with additional toxicities. E may benefit pts with KRAS-wild-type CRC, specifically those with left-sided primary tumours, and likely harms those with KRAS-mutated CRC. Further study of oral EGFR-TKIs in left-sided KRAS-wild-type aCRC is warranted.
Impact of clinical and molecular features on risk of recurrence following curative intent resection of metastases in metastatic colorectal cancer.
Authors: Burge Matthew E. , Lee Belinda , Lee Margaret , Wong Rachel , Parente Phillip , Desai Jayesh , Tran Ben , Nott Louise M. , Shapiro Jeremy David , Richardson Gary Edward , Zimet Allan Solomon , Gibbs Peter 
Published: March 2017

785 Background: Resection of metastases with curative intent is an integral component of mCRC management. However, relapse rates are high and identifying patients most likely to benefit from this approach is of considerable importance. Among patients with mCRC, mutations (mt) in RAS and BRAF genes portent a worse prognosis. Our hypothesis, therefore, is that patients harbouring these mutations may have a higher relapse rate after resection of metastases. We also wished to analyse clinical predictors of relapse, including site of metastases. Methods: We interrogated the TRACC database of patients undergoing resection with curative intent who had mutation status available. The frequency of RAS and BRAF mt was established and their association with clinical parameters determined. Relapse free (RFS) and overall survival (OS), from the date of resection, was estimated for the mt and wild type (wt) groups using the Kaplan Meier method. Multivariate analysis is planned to investigate factors associated with RFS, including stage of the primary tumour, synchronous metastases, site and number of metastases, CEA, peri-operative chemotherapy use, site of the primary (left v right) and RAS and BRAF mutation status. Results: 188 patients were identified. 89 were KRAS/BRAF wt, 92 KRAS mt and 7 BRAF mt. 40% had presented with metastatic disease and 27% had a right sided primary. 76%, 22% and 2% underwent resection of liver, lung or both metastases. Microscopic resection margin was involved in 6%. Resection was performed prior to any chemotherapy in 48%. No difference was seen in relapse free or overall survival between the mt and wt groups. Conclusions: We found no difference in relapse free or overall survival by mutation subgroup suggesting this should not influence suitability for curative intent resection, but analyses is planned on a much larger cohort once data is available. A multivariate analysis, adjusting for important prognostic variables, is planned.
Sex steroids, sex-binding globulin, and prolactin in tissues of adenocarcinoma and esophageal squamous cell carcinoma.
Authors: Kit Oleg Ivanovich , Frantsiyants Elena Mikhaylovna , Bandovkina Valeria , Kolesnikov Evgeniy N. , Myagkov Roman E. , Trifanov Vladimir , Tkalya Lyudmila Dmitriyevna , Chugunova Natalya , Tavaryan Irina Stasio 
Published: March 2017

79 Background: Some researchers suggest that squamous cell carcinoma (SCC) and adenocarcinoma of the esophagus (ACE) are characterized by different pathogenesis, epidemiology and tumor biology, and therefore require different therapeutic strategies. The purpose of the study was to analyze local hormonal status in malignant esophageal tumors and surrounding tissues depending on the histogenesis. Methods: Levels of sex steroids – free testosterone (fT), estrone (E1), estriol (E3), prolactin (PRL) and sex steroid-binding globulin (SSBG) were studied by the standard ELISA methods in tumor tissue, perifocal zone and resection line of 39 patients aged 58-74 years: 27 SCC, 12 ACE, stage II, G2, pT1-2N1M0. Results: Differences were found in local hormonal content in all studied samples dependint on the tumor histotype. Levels of SSBG, PRL and E1 in ACE were higher than in SCC by 1.3, 3.3 and 1.4 times, respectively, while fT concentration was 2.4 times lower. Levels of PRL, E1 and E3 in perifocal zone of ACE compared to SCC were higher by 2.8, 3.3 and 3.1 times, and fT was 1.3 times lower. Resection line of ACE differed from that of SCC by higher tissue concentrations of SSBG – by 1.3 times, PRL – by 1.5 times, E1 – by 1.3 times, E3 – by 1.7 times and a lower level of fT – by 1.5 times. As a result, fT/E1 ratios in ACE and surrounding tissues were on average 3 times lower than in corresponding SCC samples. Conclusions: Levels of hormones in esophageal tumors and surrounding tissues depend on the histogenesis. ACE was characterized by hyperestrogenism in esophageal tissues along with a high prolactin concentration, while SCC – by hyperandrogenism with a low PRL level. Different pathogenesis of SCC and ACE was demonstrated by the fact that hormonal profile in both tumor and resection line depended on the tumor histology.
Rectal adenocarcinoma: Outcomes of adjuvant chemotherapy after neoajuvant chemoradiotherapy in a retrospective cohort.
Authors: Pachón Olmos Vanessa , Reguera Puertas Pablo , Ferreiro Monteagudo Reyes , LONGO FEDERICO , Rodríguez Garrote Mercedes , Vaz Salgado María Ángeles , Guillen Carmen , Gion Cortés Maria , Molina CerrilloMD Javier , Martinez Saez Olga , Villamayor Delgado Maria , Die Trill Javier , Tobaruela de Blas Estela , Moreno Montes Irene , García Pérez Juan Carlos , Pina Juan Diego , Caminoa-Lizarralde Aiza María Alejandra , Sempere Ortega Cayetano , López-Campos Fernando , Carrato Alfredo 
Published: March 2017

790 Background: The role of adjuvant chemotherapy (AC) after chemoradiotherapy and surgery in stage II and III of rectal cancer is not well defined. Neither the regimen nor the duration is clear. Besides, guidelines from different expert groups are conflicting. Methods: 224 patients diagnosed from January 2003 to December 2013 with rectal adenocarcinoma T3/T4 and/or positive node staged by ultrasound or magnetic resonance imaging was collected retrospectively from the Pathology Department data base. Results: Of the 224 patients 61.6% were male, median of age at diagnosis 68.6 years (range 31.3-85.4). All of them received 50.4 Gy with different concomitant regimens (capecitabine, continuous infusion of fluoracil or bolus of fluoracil-leucovorin). 13.4% of patients achieved a pathological complete response. 76.8% of the cohort received adjuvant chemotherapy. The main reasons for not receiving chemotherapy were ECOG ≥ 2, surgery complications and a decision of the patient. 51.2% of patients received an oxaliplatin based regimen and the median time of chemotherapy duration was 4 months (range 1-6 months). Local relapse was diagnosed in 6.3% of patients while a systemic relapse was found in 22.3%. Patients without AC had a mean overall survival (OS) of 85.5 months (CI 95% 70.7-100.4) versus 119.8 monts (CI 95% 110.8-128.8) in the AC cohort (p 0.002) without reaching the median after 58 months (range 8-153.9) median follow-up. Disease free survival (DFS) was also better in the AC cohort with a mean DFS of 104 months (CI 95% 94.3-113.6) versus 71.4 months (CI 95% 55.4-87.4), p = 0.01. Conclusions: AC after chemoradiotherapy and surgery in stage II and III rectal cancer as a standard does not exist. In our cohort, AC showed a significant improve in OS and DFS, but the limitations of a retrospective study should be considered, as well as the impact of surgery on metastasis and salvage chemotherapies. Randomized studies are clearly needed.
Vitamin D levels among patients with colorectal cancer (CRC) from the San Francisco Bay area.
Authors: Savoie Marissa Barbara , Paciorek Alan T , Zhang Li , Sommovilla Nili , Atreya Chloe Evelyn , Chern Hueylan , Kelley Robin Kate , Ko Andrew H. , Sarin Ankit , Varma Madhulika G. , Abrams Donald I. , Venook Alan P. , Van Loon Katherine 
Published: March 2017

793 Background: A growing body of literature suggests that 25-hydroxyvitamin D [25(OH)D] levels are inversely related to the risk of developing CRC and that deficiency is associated with CRC-specific mortality. Due to the unique racial-ethnic diversity and UV exposure patterns of the San Francisco Bay Area, we aimed to evaluate vitamin D levels among our CRC patients at time of diagnosis and during treatment. Methods: Permanent residents of the SF Bay Area with a new diagnosis of CRC of any stage were recruited between 2011 and 2015 prior to initiation of therapy. Self-reported data on sun exposure, diet, and exercise patterns were collected. Clinical data including disease stage and primary tumor location were abstracted from charts. Serum 25(OH)D levels at time of diagnosis and at 6-month follow-up were batched and measured using the Liaison XL assay (Heartland Assays). Supplement use was not restricted. Kruskal-Wallis and Pearson correlation tests were used for categorical or continuous variables, respectively, to evaluate the associations of patient characteristics with 25(OH)D levels. Results: Among 94 patients with a new diagnosis of CRC, median 25(OH)D level at baseline was 27.0 ng/mL (range 7.2-59.0); 26% had deficient levels (<20 ng/mL), 39% had insufficient levels (<20 and <30 ng/mL), and 35% had sufficient levels (<30 ng/mL). Race, multivitamin use, vitamin D supplementation, and disease stage were associated with baseline serum 25(OH)D levels (p<0.05). The median change in 25(OH)D from baseline to six months was -0.6 ng/mL (range -19.4-51.7) for patients treated with chemotherapy (n=60) and 1.6 ng/mL (range -6.4-33.2) for patients who did not receive chemotherapy (n=19) (p=0.51). Conclusions: Among patients with a new diagnosis of CRC in the San Francisco Bay area, vitamin D insufficiency was seen in more than half of patients, consistent with reports from other geographic areas. Allowing for vitamin D supplementation, serum 25(OH)D levels did not decrease significantly after 6 months of chemotherapy. We are routinely screening CRC patients for 25(OH)D insufficiency at time of diagnosis and during treatment.
A retrospective analysis on the impact of preoperative neutrophil to lymphocyte ratio in stage II colon cancer.
Authors: Jaiswal Deepna , Mantha Suparna , Wong Lucas , Seija Luis , Munoz Yolanda 
Published: March 2017

794 Background: Inflammation has a critical role in tumor genesis and progression of cancer. The neutrophil to lymphocyte ratio (NLR) is an indication of balance between the immune systems pro and defense mechanism against cancer. Elevated NLR is of interest in many cancers, including colon cancer. Although surgery is the mainstay of treatment for early stage colon cancer, adjuvant chemotherapy for stage II colon cancer has remained debatable. We proposed to study the impact of the NLR in patients with stage II colon cancer and to identify high risk patients who would benefit from adjuvant chemotherapy. Methods: Three hundred and eighty patients diagnosed with Stage II colon cancer at our institution were included in this retrospective study. Kaplan-Meir curves and multivariate Cox-regression analyses were calculated for overall survival. Results: Univariate analysis showed NLR was not statistically significant as predictor of mortality (p-value=0.0857). However, after adjusting for recurrence, chemotherapy, age, white blood cell count, the NLR was predictive for survival, with a hazard ratio of 1.05 and 95% confidence interval of (1.006 - 1.1). Recurrence and age were also significant predictors of survival (p-values of <0.0001 for both), and HR of 3.1 (2.0 – 4.6) and 1.4 (1.2 – 1.5), respectively. Conclusions: The neutrophil to lymphocyte ratio might be an independent prognostic marker for overall survival in stage II colon cancer patients. Given the retrospective nature of our study, further studies are indicated to confirm our findings.
Exploratory evaluation of pharmacodynamic biomarkers and pharmacokinetics (PK) of ziv-aflibercept (Z) + FOLFIRI in a phase II study of Japanese patients (pts) with metastatic colorectal cancer (mCRC).
Authors: Yoshino Takayuki , Sugimoto Naotoshi , Yamazaki Kentaro , Kajiwara Takeshi , Komatsu Yoshito , Sasaki Toru , Chiron Marielle , Ziti-Ljajic Samira , Brillac Claire , Hamaguchi Tetsuya 
Published: March 2017

799 Background: Z + 5-fluorouracil/levofolinate/irinotecan (FOLFIRI) is a 2nd-line treatment for mCRC. There are no established biomarkers that predict response to this treatment. This study aimed to identify such biomarkers. Methods: 62 pts with mCRC received Z (4 mg/kg) + FOLFIRI every 2 weeks. 78 potential protein biomarkers (e.g., cytokines) were chosen for analysis based on their roles in angiogenesis, tumor progression, and tumor-stroma interaction. Plasma levels of biomarkers at baseline and pre-dose 3 (Day 1 of Cycle 3) were measured in all pts by enzyme-linked immunosorbent assays. Relationships between these levels and efficacy endpoints were assessed. PK data were calculated. Results: 10 potential biomarkers had a ±30% change from baseline to pre-dose 3 (adjusted P < .001); the greatest changes were in placental growth factor (median: 4,716%) and vascular endothelial growth factor receptor 1 (2,171%). Baseline levels of 8 potential biomarkers correlated with overall survival (OS; see table) in a univariate Cox regression analysis; none correlated with progression-free survival or maximum tumor shrinkage. Pre-dose 3 levels did not correlate with any efficacy endpoints. Conclusions: Preliminary data show that these 8 biomarkers could be associated with OS. No significant drug interactions were found. Clinical trial information: NCT01882868. [Table: see text]
Efficacy of panitumumab plus irinotecan versus cetuximab plus irinotecan in patients with wild-type KRAS exon2 metastatic colorectal cancer previously treated with bevacizumab within 6 months.
Authors: Hayashi Kaori , Mitani Seiichiro , Taniguchi Hiroya , Hamauchi Satoshi , Sugiyama Keiji , Tsushima Takahiro , Honda Kazunori , Todaka Akiko , Masuishi Toshiki , Yokota Tomoya , Narita Yukiya , Machida Nozomu , Kadowaki Shigenori , Fukutomi Akira , Ura Takashi , Onozawa Yusuke , Ando Masashi , Yasui Hirofumi , Muro Kei , Yamazaki Kentaro 
Published: March 2017

800 Background: The ASPECCT study showed panitumumab (Pmab) is non-inferior to cetuximab (Cmab) for chemotherapy-refractory and intolerant wild-type (WT) KRAS exon2 metastatic colorectal cancer (mCRC). In the subgroup analysis, Pmab provided more favorable outcomes than Cmab for patients (pts) previously treated with bevacizumab (Bmab). However, some reports suggested that anti-EGFR antibody (anti-EGFR) efficacy was reduced when received within 6 months of last administration of Bmab. In this study, we aim to evaluate the difference in efficacy between Pmab and Cmab in pts who received prior Bmab and were treated with anti-EGFR after a short interval. Methods: We retrospectively evaluated pts treated with anti-EGFR and irinotecan (IRI) after failure of Bmab, fluoropyrimidine, oxaliplatin, and IRI at two institutions. The main inclusion criteria were WT KRAS exon2 mCRC, ECOG PS 0-2, and no prior administration of anti-EGFR within 6 months after Bmab. Results: From Sep. 2008 to Mar. 2016, 124 consecutive pts met the inclusion criteria (Pmab/Cmab, 30/94). Pts’ characteristics were as follows (Pmab/Cmab): median age (range): 63/62 (38-76/27-82); male, 63%/72%; ECOG PS 0, 43%/27%; PS1, 57%/66%; PS2 0%/7%; tumor in left colon, 87%/76%; histology (por, muc), 10%/16%; ≥2 metastases, 67%/66%; ≥1 subsequent therapy, 73%/63%. Overall response and disease control rates in Pmab/Cmab were 31%/26% and 69%/67%, respectively. In Pmab/Cmab, the median overall survival was 15.8/12.2 months (HR, 0.62; 95% CI, 0.4-0.97; P=0.04) and the median progression-free survival was 6.5/5.5 months (HR, 0.75; 95% CI, 0.49-1.16, P=0.20). The adjusted HR with 10 covariates such as age, gender, PS, tumor location, histology, primary tumor resection, number of metastatic sites, liver limited disease, time from diagnosis of metastasis and initiation date of anti-EGFR plus IRI was 0.61 for PFS (p=0.1) and 0.61 for OS (p=0.04). Conclusions: Pmab plus irinotecan showed favorable outcomes compared with Cmab plus irinotecan in pts with WT KRAS exon2 mCRC within 6 months between the last administration of Bmab and initial anti-EGFR.
Gender differences in hormonal statuses of patients with esophageal squamous cell carcinoma.
Authors: Kolesnikov Evgeniy N. , Kit Oleg Ivanovich , Frantsiyants Elena Mikhaylovna , Bandovkina Valeria , Kozlova Margarita , Cheryarina Natalia D. , Mezentsev Stanislav Stanislavovich , Snezhko Alexander V. 
Published: March 2017

85 Background: Esophageal squamous cell carcinoma (ESCC) is 4-8 times more frequent in men than in women, with poorer prognosis. The purpose of the study was to analyze systemic and local hormonal statuses in patients with ESCC in dependence on their gender. Methods: The study included 34 ESCC (G2, рT1-2N0-1M0) patients: 21 men and 13 women. 11 men (52.4%) had lymph node metastases. Levels of sex steroids – total (T) and free (fT) testosterone, progesterone (P4), estradiol (E2), estrone (E1), prolactin (PRL), LH, FSH and sex steroid-binding globulin (SSBG) – were studied in the peripheral blood, tumor and resection line by the standard RIA and ELISA methods. Results: Men showed a decrease in the blood T concentration by 1.4 times, P4 by 2 times, and E2 increase by 2.5 times, while women showed 1.3 times increase in T and 2 times decrease in P4. Metastases in men were accompanied by an increase in blood levels of anterior pituitary hormones: PRL by 2.5 times, LH by 2.3 times and FSH by 2.2 times compared to patients without metastases. Analysis of the local saturation with sex hormones in visually unchanged esophageal tissues of ESCC patients did not reveal any significant gender difference. However, women were characterized by a higher content of anterior pituitary hormones, PRL, LH and FSH, in esophageal tissues compared to men. Men with metastases showed local hyper-androgenization of tumor and surrounding tissues, as the fT to E1 ratio was increased. Conclusions: The results confirmed the data on T-stimulation of malignant growth in the esophagus and the possible protective effect of estrogens. The free testosterone to estrogens ratio in esophageal tissues can probably serve as one of prognostic factors for the disease course.
Thrombospondin-1 expressions in non-cancer tissue correlated with gastric carcinogenesis.
Authors: Kashihara Hideya , Shimada Mitsuo , Yoshikawa Kozo , Higashijima Jun , Nishi Masaaki , Takasu Chie 
Published: March 2017

88 Background: Thrombospondin-1 (TSP1) correlated with the carcinogenesis in the intestinal inflammation. TSP1 binding CD36 evoked inflammation via the activation of TGFβ and STAT3. The aim of this study is to clarify the role of TSP1 in gastric carcinogenesis. Methods: Thirty-nine patients with gastric cancer who underwent gastrectomy were enrolled. The expression of TSP1 mRNA in non-cancer tissue was determined in clinicopathological factors (including mucosal inflammation and atrophy based on Sydney system). The expressions of CD36, STAT3 and TGFβR2 mRNA in the TSP1 high and low expression group in non-cancer tissue were examined. Results: TSP1 expression was high in mucosal atrophy group and tended to be high in Helicobacter pylori (H.pylori) (+) and multiple cancer group. In TSP1 high group, CD36, STAT3 and TGFβR2 mRNA showed significantly high. The expressions of TSP1 signaling pathway in multiple cancer or atrophy (+) or H.pylori (+) showed high compared with that in single cancer and atrophy (-) and H.pylori (-). The expressions associated TSP1 signaling pathway in non-cancer tissue with multiple gastric cancer showed higher than that with single gastric cancer. Conclusions: Our results indicated TSP1 expressions in non-cancer tissue correlated with gastric carcinogenesis.