bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective analysis of clinical characteristics of mCRC patients receiving three or more lines of chemotherapy.
Authors: Garcia Alfonso Pilar , Martínez Delfrade Íñigo , Soto Alsar Javier , Bringas Beranek Marianela , Gutiérrez Alonso Natalia , Ortega Laura , Torres Gabriela , Muñoz Martín Andres J. , Blanco-Codesido Montserrat , Calvo Aitana , Martin Miguel 
Published: January 2019

682 Background: Prognostic and predictive factors are becoming more important in mCRC patients, and may have an impact in overall survival and in the number of lines of chemotherapy that a patient can receive. Methods: We conducted a retrospective analysis of 334 patients with mCRC. We analyzed the clinical characteristics of 113 (33.8%) mCRC patients who received ≥3 lines of chemotherapy. We apply the statistical test Chi square in order to identify significant association. Results: Several characteristics were significantly associated with receiving ≥ 3 lines of chemotherapy (n = 113): age < 80 years (n = 93, OR = 3.07, p = 0.001), ECOG 0-1 (n = 98, OR = 3.21, p = 0.055), primary tumor resection (n = 62, OR = 2.36, p = 0.000) and resection of metastases (n = 56, OR = 2.07, p = 0.002). Partial or complete response rate in the first line of chemotherapy was also significantly associated with receiving ≥ 3 lines of treatment (n = 65, p = 0.011). Tumor mutational status was analyzed in 333 patients: KRAS mutation was detected in 163 over 333 patients genotyped (48.9%), NRAS in 25/206 (12.1%), BRAF in 15/217 (6.9%) and PI3K in 31/213 (14.5%). In the group of patients receiving ≥ 3 lines of chemotherapy (n = 113): KRAS mutation was found in 60/113 patients (53.1%), NRAS in 5/77 (6.5 %), BRAF in 5/84 (5.9%) and PI3K in 8/80 (11.1%). Tumor mutations were not significantly associated with ≥ 3 lines of chemotherapy. No significant association was found between sex, tumor location (right [n = 33, 29.2%] or left [n = 76, 73%]), liver or lung isolated metastases and 3 or later lines of chemotherapy. We also performed in our database a survival analysis in the 334 patients: those who received ≥3 lines of chemotherapy had significantly higher survival rates (median OS 18 m in the group of < 3 lines of treatment vs. 37.2 m in the group of ≥ 3 lines of chemotherapy, HR = 1,6; CI 95% 1,2-2.1; p < 0,001). Conclusions: This retrospective analysis showed that mCRC patients with < 80 years, ECOG 0-1, primary tumor and or metastases resected and those with complete or partial response in the first line of treatment have a higher probability of receiving ≥ 3 lines of chemotherapy. [Table: see text]
Trecc: Re-challenge therapy with anti-EGFR in metastatic colorectal adenocarcinoma (mCRC).
Authors: Karani Amanda , Felismino Tiago , Diniz Lara Azevedo , Macedo Mariana Petaccia , Machado Larissa , De Brito Sales Diogo , Mello Celso Lopes 
Published: January 2019

683 Background: Anti-EGFR plus chemotherapy (CT) promotes high response rates (RR) and median overall survival (OS) surpasses 30 months in RASwt/BRAFwt mCRC. After disease progression (PD), resistance mechanisms have been described. The aim of our study was to evaluate efficacy of anti-EGFR re-challenge (TRECC). Methods: We retrospectively analyzed a cohort of patients (pts) with mCRC. All pts had received anti-EGFR plus CT and were discontinued for different reasons. During the treatment, there was re-challenge with an anti-EGFR + CT. We aimed to evaluate progression-free survival (PFS) and OS after re-challenge and prognostic factors associated with PFS. Results: Sixty eight pts met the study criteria. Median follow-up after re-challenge was 39.3m. Discontinuation after first exposure was 25% due to PD; 75% for other reasons. Median anti-EGFR free interval was 10.5m. At re-challenge, main CT regime was: FOLFIRI 58.8%, Cetuximab and Panitumumab were used in 59 and 9 pts respectively. mPFS after re-challenge was 6.6m; mOS was 24.4m. Objective response rate (CR + PR) at re-challenge was 42.6%. In an univariate analysis, adverse prognostic factors related to PFS were: absence of objective response at 1st EGFR exposure (HR 2.12, CI:1.20-3.74 p = 0.009); PD as reason for 1st discontinuation (HR 3.44, CI:1.88-6.29 p < 0.0001); re-challenge at fourth or later lines (HR 2,51, CI:1.49-4.23 p = 0.001); panitumumab use (HR 2.26 CI:1.18-5.54 p = 0.017). In a multivariate model, only PD as reason for 1st discontinuation remained statistically significant (HR = 2.63, CI:1.14-6.03 p = 0.022). mPFS was 3.3m and 8.4m and mOS was 7,5m and 33,4m in patients with PD as reason for 1st discontinuation and other reasons respectively. Conclusions: Re-challenge therapy is commonly used due to paucity of effective lines of treament for mCRC. In our analysis, pts that stopped 1st anti-EGFR therapy due to PD have shorter survival, suggesting these pts do not benefit from TRECC. However, interruption due to treatment holiday after PR/CR resulted in longer PFS. In conclusion, for a selected group of pts, TRECC could be considered a strategy of treatment. Due to the limited number of pts, our data should be evaluated in a prospective cohort of patients.
Impact of sarcopenia on outcomes in patients with rectal carcinoma treated with trimodality therapy.
Authors: Sandoval Maria Luisa , Yuan Zhigang , Grass G. Daniel , Felder Seth , Sanchez Julian , Dessureault Sophie , Imanirad Iman , Kim Richard D. , Hoffe Sarah E. , Frakes Jessica 
Published: January 2019

687 Background: Sarcopenia has been identified as a negative prognostic factor in several gastrointestinal malignancies. We sought to evaluate whether total psoas area (TPA) was predictive of grade ≥ 3 toxicity, recurrence and overall survival in patients with rectal carcinoma who received tri-modality therapy. Methods: After IRB approval, a retrospective analysis of 112 patients with biopsy-proven rectal cancer treated with neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy was performed. The L4 vertebra was identified on pre-treatment axial CT and the bilateral psoas muscles were manually contoured to determine the skeletal muscle index, which was normalized by height. Sarcopenia was defined as TPA less than the median of the cohort. (< 1463 mm3/m). Acute toxicity was defined as within 3 months of radiation based on Common Terminology Criteria for Adverse Events version 4. Chi-square was used to assess differences between groups. Time to event analysis was estimated by Kaplan-Meier methods followed by log rank comparison. Predictor variables for outcomes were assessed with Cox regression. Results: Median follow-up was 31 months. Female gender was strongly associated with being sarcopenic (P < 0.001) otherwise no other differences in clinical or treatment characteristics were found. 20 patients (17.8%) developed recurrence (95% distant). Patients with sarcopenia had a decreased risk of recurrence (P = 0.048) as well as a longer time to recurrence from radiation (50 vs. 21.4 months, P = 0.006) and surgery (47.2 vs. 17.9 months, P = 0.006). Gender was not associated with risk of recurrence (p = 0.131). On multivariable analysis, absence of sarcopenia was predictive of time to recurrence following radiation (HR 4.7, 95% CI: 1.2-18.8; P = 0.03). The presence of sarcopenia was not associated with overall survival (P = 0.12) or grade ≥ 3 acute toxicity (P = 0.242). Conclusions: In our cohort, patients with sarcopenia appear to have better tumor control when compared to patients without sarcopenia independent of gender, suggesting this may be a predictor of treatment response. However, sarcopenia was not associated with overall survival or probability of having grade ≥ 3 acute toxicity.
Updated results of the BEACON CRC safety lead-in: Encorafenib (ENCO) + binimetinib (BINI) + cetuximab (CETUX) for BRAFV600E-mutant metastatic colorectal cancer (mCRC).
Authors: Kopetz Scott , Grothey Axel , Yaeger Rona , Cuyle Pieter-Jan AR , Huijberts Sanne , Schellens Jan H. M. , Elez Elena , Fakih Marwan , Montagut Viladot Clara , Peeters Marc , Desai Jayesh , Yoshino Takayuki , Ciardiello Fortunato , Wasan Harpreet Singh , Maharry Kati , Christy-Bittel Janna , Gollerkeri Ashwin , Van Cutsem Eric , Tabernero Josep 
Published: January 2019

688 Background: BRAFV600E mutation occurs in 10%-15% of patients (pts) with mCRC and confers a poor prognosis. After first-line therapy, standard second-line therapies provide limited benefit, with objective response rates (ORRs) < 10%, and overall survival (OS) of 46 months (mo). BEACON CRC (NCT02928224) is a 3-arm phase 3 trial of triplet therapy with the BRAF inhibitor ENCO + MEK inhibitor BINI + antiEGFR antibody CETUX vs ENCO + CETUX vs a control arm (irinotecan/FOLFIRI + CETUX) in pts with BRAFV600E mCRC in the second or third-line setting. A safety lead-in (SLI) of the triplet therapy was conducted in 30 pts prior to initiation of the randomized part of the trial. Previously reported confirmed ORR in 29 pts with BRAFV600E mCRC was 48% and median progression-free survival (PFS) was 8.0 mo (Van Cutsem E, et al. Ann Oncol. 2018;29:O-027). Here we present updated safety and efficacy results including mature OS. Methods: All pts in the SLI received ENCO 300 mg once daily + BINI 45 mg twice daily + CETUX standard weekly dose. Assessments included efficacy (ORR, duration of response, time to response, PFS, and OS), safety, and tolerability. Results: Among 30 pts treated, 1 had a BRAF non-V600E mutation and is not included in the efficacy analyses. At data cutoff, the median follow-up time for survival was 18.2 mo and median exposure was 7.8 mo (range 0.521.4 mo). The confirmed ORR and median PFS remain unchanged from the previous report (ORR, 48% [95%CI, 29.467.5]; PFS, 8.0 mo [95% CI, 5.69.3 mo]). Mature median OS is 15.3 mo (95% CI, 9.6 monot reached). The triplet continues to be well-tolerated with no unexpected toxicities. The most common grade 3/4 toxicities were fatigue (13%), anemia, increases in creatine phosphokinase and/or aspartate aminotransferase, and urinary tract infections (each 10%). The rate of grade 3/4 skin toxicities continues to be lower than generally observed with CETUX in mCRC. Conclusions: With longer follow-up, triplet therapy with ENCO + BINI + CETUX continues to be well tolerated. Median PFS and now mature median OS are substantially improved over historical data for current standard-of-care options. Clinical trial information: NCT02928224.
HIPEC scoring system: A preoperative model including clinical and radiographic parameters to improve patient selection.
Authors: Gauvin Gabrielle , Kilcoyne Maxwell , Ang Kwan-Keat , Selesner Leigh T , Egleston Brian L. , Farma Jeffrey M. , Sigurdson Elin R. , Reddy Sanjay S. 
Published: January 2019

695 Background: Most studies looking at long-term outcomes in patients undergoing cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CS/HIPEC) are based on scoring systems performed at the time of the operation. With a morbidity as high as 67%, it is crucial to carefully choose the patients who will benefit from this procedure. In this study, we evaluated preoperative factors that could impact patient outcomes. Results were used to create a predictive model for patients considered for CS/HIPEC. Methods: Patients assessed for CS/HIPEC at our tertiary cancer center between 2012 and 2017 were considered for this study. Postoperative complications, recurrence free survival (RFS) and overall survival (OS) were used as endpoints, and multivariable analysis accounting for demographics, clinical, bloodwork, radiologic and pathologic findings was performed. Results: Sixty-eight patients were considered for CS/HIPEC. Preoperative elements found to have an impact on OS were lymph node involvement (p = 0.001) and high extent of carcinomatosis (p < 0.001) on computed tomography (CT) scan. Findings that impacted RFS were lymphovascular invasion (p = 0.042), lymph node involvement (p = 0.061) and omental caking (p = 0.010) on CT. Our preoperative predictive model is presented in table. An increased rate of complications was seen in smokers (p = 0.031), obese patients (p = 0.005) and carcinomatosis diagnosed ≤ 12 months from the primary diagnosis (p = 0.069). In our experience, performing CS/HIPEC did improve OS (p = 0.036) after adjustment for age, race, smoking, and BMI. Conclusions: Preoperative findings could help physicians in their discussions with patients prior to pursue CS/HIPEC. These interesting findings will be used to inform the next step of our study: a prospective clinical trial. [Table: see text]
A multivariate model to define risk groups among patients with curatively resected stage I and II colon carcinoma: Final report of a retrospective cohort study.
Authors: Onate-Ocana Luis F. 
Published: January 2019

696 Background: Patients with stage I or II colon carcinoma (CC) have a 10 or 20% risk, respectively, of presenting recurrent disease after a potentially curative surgical resection and adjuvant chemotherapy have not improved survival in this setting. In this study, we present a multivariate model to define risk groups. Methods: Consecutive cases with stage I and II CC treated at a single cancer center in Mexico City, from January 1992 to December 2016, were included in this 25-year cohort. Clinical history and biochemical data were registered, and colon resection was performed with curative intention with standard lymphadenectomy. Standard hematoxylin-eosin slides and CDX2 immunohistochemistry (IHC) slides were analyzed by two independent pathologists. The Kaplan-Meier method and Cox model were used to analyze the association of prognostic factors and overall survival (OS). Results: 3,301 cases of colorectal cancer were treated during this study, but only 556 patients with stage I and II CC were included in the database: 266 women (47.8%) and 290 males (52.2%) (mean age 57.9 years); 52 (9.4%), 431 (77.5%), 36 (6.5%) and 37 (6.7%) were pTNM stages I, IIa, IIb, and IIc, respectively. R0 resection was performed in 548 patients (98.6) and R1 in 8 (1.4%). Location in the left colon (HR 1.63), hemoglobin (HR 0.93), serum albumin (HR 2.45), prognostic nutritional index 0.915), platelet count (HR 0.998), body mass index (HR 0.94), basal carcinoembryonic antigen (HR 1.0), TNM stage [stage I reference category, IIa (HR 5.46), IIb (HR 4.42), IIc (HR 9.28)], R1 residual disease (HR 2.8), negative CDX2 IHC (HR 2.1), and use of adjuvant chemotherapy (HR 0.629) were included in the final model as independent predictors of OS (model p < 0.0001).Predicted survival functions using this model defined three distinct risk groups. Conclusions: This multivariate model adds significant prognostic value to the pTNM classification. This model can be useful for stratifying prognosis in patients with CC and will aid in the design of randomized clinical trials evaluating the usefulness of adjuvant chemotherapy in this subgroup of patients with CC.
Assessing hematologic ratios as biomarkers for psychosocial distress.
Authors: Fong Abigail , Lafaro Kelly , Li Arthur X , Melstrom Laleh Golkar , Rodriguez Jenny , Clark Karen L. , Loscalzo Matthew J. , Warner Susanne 
Published: January 2019

699 Background: Psychosocial distress is common among cancer patients and has been shown to have deleterious effects on a patient’s quality of life, treatment, and outcomes. Neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), and platelet-monocyte ratio (PMR) have been associated with poor outcomes in some cancers. Therefore we hypothesized that these ratios may be correlated to distress. This study looked at request for social work follow up as a surrogate marker for distress and investigated relationships between these ratios and markers of patient distress. Methods: A validated 48 item electronic distress screen was administered to patients in the medical and surgical oncology clinics of a large cancer center from 2009-2015. Patient requests for social work follow up were noted and patient charts reviewed for relevant labs and history. Patient demographics, NLR, LMR, PMR were reviewed. Chi-squared tests and univariate and multivariate regressions were performed to compare groups and relationships of variables and outcomes. Results: 43% of patients surveyed requested social work follow up. Of those, 75% received follow up, at a mean of 8 days. Non-Caucasian patients were more likely to request social work follow up (p = 0.03). Non-English speaking patients (p = 0.06) and those who saw medical oncologists trended towards significant desire for social work follow up. There was no significant correlation between NLR, PMR, LMR and desire to see a social worker. On multivariate analysis, patients with metastatic disease were less likely to want social work follow up (OR 0.43, 95% CI: 0.21-0.9, P = 0.02). Conclusions: In this study, non-white, non-English speaking patients, and those seeing medical oncologists were more likely to request social work follow up. We found no significant correlations between NLR, PMR, LMR and request for social work follow up. This suggests that desire for social work follow up is not a good correlate for physiologic distress in cancer patients. Further work is ongoing to provide better insight into determinants of psychosocial and physiologic stress in this patient population along with relevance of hematologic ratios.
Parallel-group controlled trial of esophagectomy versus chemoradiotherapy in patients with clinical stage I esophageal carcinoma (JCOG0502).
Authors: Kato Ken , Igaki Hiroyasu , Ito Yoshinori , Nozaki Isao , Daiko Hiroyuki , Yano Masahiko , Ueno Masaki , Nakagawa Satoru , Takagi Masakazu , Tsunoda Shigeru , Abe Tetsuya , Nakamura Tetsu , Hihara Jun , Toh Yasushi , Shibuya Yuichi , Mizusawa Junki , Katayama Hiroshi , Nakamura Kenichi , Kitagawa Yuko ,   Japan Esophageal Oncology Group of Japan Clinical Oncology Group (JCOG)
Published: January 2019

7 Background: Esophagectomy (E) is the standard of care for stage I esophageal squamous cell carcinoma (ESCC), while chemoradiotherapy (CRT) is a treatment option. A parallel-group controlled trial including randomized arms to confirm the non-inferiority of CRT to E for stage IA ESCC was conducted. Methods: Patients (pts) with thoracic ESCC, adenosquamous cell, or basaloid cell carcinoma with stage IA (T1bN0M0), age 20 to 75, performance status 0 to 1, and adequate organ function were eligible. If pts accepted randomization, they were randomly allocated to E with 2-3 field lymph node dissection (arm A) or CRT (arm B). However, if pts had a preference and refused randomization, they were allocated to pts preference arm, E (arm C) or CRT (arm D). CRT consisted of cisplatin and 5-FU, with radiation at the dose of 60 Gy concurrently. The primary endpoint was overall survival (OS) of arm A and B, secondary endpoint included OS of arm C and D using inverse probability weighting with propensity score. The planned sample size in arm A and B was 114 pts in total with one-sided alpha of 10%, power of 75% and non-inferiority margin of HR as 1.78. The sample size in arm C and D was at least 156 pts in each arm with one-sided alpha of 2.5%, power of 85% and non-inferiority margin of HR as 1.78. Results: Between December 2006 and February 2013, 379 (Arm A: 4, B: 7, C: 209 C, D: 159) pts were enrolled. Primary endpoint was not calculated due to small number of randomized arms. Patients characteristics of arm C and D were as follows; median age: 62 and 65, male (%): 82.8 and 88.1, PS 0 (%): 99.5 and D 98.1. All histologic type was SCC except one basaloid cell carcinoma in arm C. The 3- and 5-year OS were 94.7% and 86.5% in arm C, and 93.1% and 85.5% in arm D (adjusted HR 1.05; 95% CI 0.67-1.64 [< 1.78]).Treatment related death were observed in two pts in arm C and none in arm D. Conclusions: Though the accrual of randomized arms was shortened, CRT showed trend toward non-inferiority compared to E in pts preference arms. CRT is considered as a treatment option for stage IA ESCC with organ preservation. Clinical trial information: UMIN000000551.
The relationship between aortoiliac calcification and long-term outcome in rectal cancer resection.
Authors: Knight Katrina , Boland Kate , McMillan Donald C , Horgan Paul G. , Roxburgh Campbell SD , Park James Hugh 
Published: January 2019

705 Background: The interaction between host and tumour factors is an important determinant of long-term outcome following rectal cancer resection. At cellular level, hypoxia within the tumour microenvironment stimulates neovascularisation, alters tumour metabolism and is implicated in dissemination and metastases. At host level, restricted blood flow to the tumour may play a role in tumour hypoxia. Significant calcification of the distal aortic and iliac arteries could result in impaired rectal perfusion. We aimed to investigate the relationship between aortoiliac calcification (AC) and long-term outcome following rectal cancer resection. Methods: Patients were identified from a prospectively maintained database. Recurrence and survival data were abstracted. On staging CT images, the sum of calcified quadrants of the distal aorta and iliac arteries at the level of the bifurcation was calculated. ROC analysis was used to identify the optimum threshold for determining significant calcification. Results: Between 2008-2016, 181 patients with available CT scans underwent surgery for rectal cancer. Most were male (60%), aged over 65 (53%) and TNM stage II/III (72%). Median follow-up was 63 months. Significant AC was identified in 44 patients (24%). Recurrence occurred in 42 patients: local in 16 (9%) and systemic in 26 (14%) patients. Recurrence was associated with significant AC (p = 0.017), TNM stage (p = 0.002) and venous invasion (p = 0.006). When considering those with and without significant AC, there were differences in the rates of local (11% vs. 8%) and systemic (25% vs. 11%) recurrence respectively (p = 0.043). On univariate Cox regression analysis, overall survival was related to age (p = 0.012), ASA grade (p = 0.042) and significant AC (p = 0.001). On multivariate analysis, significant AC (p = 0.011) was the only independent predictor of overall survival. Conclusions: The burden of aortoiliac calcification appears to play an important role in influencing long-term outcome following rectal cancer resection, independent of traditional determinants such as TNM stage and ASA grade. While validation is required, further investigation of the mechanism underlying this relationship is warranted.