bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective analysis of dose intensity, toxicity, and clinical outcomes in 5-fluorouracil (5FU)-based regimens in adjuvant treatment of colon cancer.
Authors: Loree Jonathan , Mulder Karen E. , Ghosh Sunita , Spratlin Jennifer L. 
Published: March 2020

e14575 Background: Adjuvant colon cancer treatment relies on 5FU containing regimens as either an IV formulation or as the oral pro-drug, capecitabine, combined with oxaliplatin (FOLFOX6 and CAPOX). We performed a retrospective chart review comparing average relative dose intensity (ARDI), overall survival (OS), disease free survival (DFS), and toxicity profiles of these two regimens. Methods: 233 patients between January 1, 2006 and December 31, 2011 received chemotherapy combining either FOLFOX6 (n= 128) or CAPOX (n=105) in Edmonton, Alberta. ARDI was compared by calculating a percent of target dose achieved in the average cycle for each patient. Data on OS, DFS, baseline demographics, and toxicities were gathered. Survival data was plotted using the Kaplan-Meier method and compared using the log-rank test. Variable comparisons were performed with the Student’s t-test or the Fisher’s Exact test. Follow up was complete until November 1, 2012. Results: Oxaliplatin ARDI was significantly lower in those treated with CAPOX compared to FOLFOX6 (80.72% vs 87.11%, p=0.0033), as was the 5-FU component (87.10% vs 93.60%, p<0.0001). More patients treated with CAPOX had dose limiting toxicities (84.76% vs 73.40%, p=0.039), and there were significantly more Grade 2 and higher toxicities in those on CAPOX (p<0.0001). A similar percentage of goal number of cycles was achieved between CAPOX and FOLFOX6 (87.38% vs 91.80%, p=0.13) and similar neuropathy was noted between groups. Survival analysis demonstrated similar OS and trends towards improved DFS with CAPOX (1 year – 89.55% vs 83.20%, 3 year – 67.13% vs 58.01%, p=0.051). Stage specific analysis showed stage III patients had improved DFS with CAPOX (1 year – 93.36% vs 86.69%, 3 year- 71.58% vs 68.10%, p=0.042) and trends towards improved OS with CAPOX (1 year – 100% vs 95.56%, 3 year – 95.08% vs 80.17%, p=0.16). The groups had similar age, gender, tumor size, and node status, while ECOG was slightly higher with FOLFOX6 (0.589 vs 0.419, p=0.0315). Conclusions: While patients on CAPOX had significantly lower doses of oxaliplatin and the 5-FU component of their treatment they appear to have improved outcomes compared to FOLFOX6.
Palliative chemotherapy in advanced colorectal cancer patients age 80 or older.
Authors: Lai Pamela , Sud Shelly , Zhang Tinghua , Asmis Timothy R. , Wheatley-Price Paul 
Published: March 2020

e14598 Background: Colorectal cancer (CRC) is the second most common cancer worldwide, with a median age at diagnosis of 71 years. While there has been significant progress in chemotherapy (CT) options for metastatic CRC (mCRC) patients (pts) over the past decade, there is very little data on outcomes or toxicity from CT in mCRC pts aged ≥80 years. We investigated palliative CT in the 80+ mCRC population, hypothesizing that high rates of hospitalization and toxicity may be observed. Methods: With ethics approval, a retrospective chart review was conducted of pts ≥80 years with mCRC who initiated a CT course between June 2005 and November 2009 at our institution. Baseline data on pt demographics were collected, in addition to CT data. The endpoints included: rates of hospitalization, CT discontinuation due to toxicity, and overall survival (OS). Results: CT was initiated on 88 occasions during the study period. The median age was 83 (range 80-92) and 52% of pts were male. Where data were available, 60% of pts had a good performance status (PS) of ECOG 0-1, 20% PS 2 and 9% PS 3 (10% unknown). 63 pts (72%) lived with family and 23% lived alone. 76% had a Charlson Comorbidity Index (CCI) ≥7 and 31% were taking ≥6 baseline prescription medications. At baseline, 33% of pts were anemic (Hgb <100), 36% had leukocytosis (WBC>11) and 48% had renal impairment (eGFR <60). Palliation was the intent for 95% of cases and 47 pts (53%) were receiving first line CT. The initial CT dose was adjusted from standard of care in 67% of cases. The most common CT was capecitabine monotherapy (45%). In total 19 pts (22%) were hospitalized during or within 30 days of CT; 26 pts (30%) discontinued CT due to toxicity, and 48 pts (55%) required at least 1 dose reduction, delay or omission. The median OS was 14.6 months (95% CI 11.7-18.6). No baseline factors (age, sex, PS, CCI, line of CT, baseline dose adjustment, baseline blood work) were associated with hospitalization, CT discontinuation due to toxicity, or OS. Conclusions: Palliative CT for mCRC in the ≥80 population is feasible, but most pts will require dose adjustments, and a significant minority will be hospitalized or stop CT due to toxicity. Prospective research incorporating geriatric assessment tools is required.
Panitumumab after progression on cetuximab in patients with KRAS wild-TYPE (WT) metastatic colorectal cancer (MCRC): A single institution experience.
Authors: Marino Antonella , Caliolo Chiara , Sponziello Francesco , Nacci Angelo , Quaranta Annamaria , Mazzoni Enrica , Federico Federica , Rizzo Pietro , Calvani Nicola , Orlando Laura , Schiavone Paola , Fedele Palma , D' Amico Maria , Chetrì Maria Concetta , Cinefra Margherita , Ferrara Pasqualinda , Cinieri Saverio 
Published: March 2020

e14605 Background: Cetuximab and panitumumab are monoclonal antibodies that target EGFR, approved for the treatment of KRAS WT MCRC. Few data describe the activity of panitumumabafter cetuximab-irinotecan based regimen failure. Methods: The aim of this study is to assess if panitumumab has some activity in pts with KRAS WT MCRC that has progressed on prior cetuximab. Results: We retrospectively analysed 25 pts with KRAS WT MCRC who received from 07/2009 to 01/2013 panitumumab after progression on cetuximab. Median age: 63 yrs (40-78), primary site tumor: colon 64%, rectum 36%; synchronous metastases 36%, metachronous 64%. Sites of metastases: liver 44%, liver and lung 8%, other sites 48%. All pts had previously received cetuximab associated with irinotecan (20 pts) or oxaliplatin (5 pts) and subsequently received panitumumab. We withdrew cetuximab because of intolerance in 4 pts (16%), while 21 pts (84%) with ECOG PS 0-1 who had previously responded to cetuximab (ORR plus SD lasting more than 5 months) received panitumumab “off-label” after progression on cetuximab because strongly motivated to continue treatment. Median cycles of panitumumab were 7 (1-54). Only eighteen pts were evaluable for ORR (4 pts received 1-2 cycles and then died, 3 pts too early). We observed one PR (5%); five pts (28%) had SD, median duration 9 months. Median PFS was 5 months (3-28) and median OS 8 months (5-41). All pts were evaluable for toxicity. No pts developed anemia, nor neutropenia. One patient (4%) developed grade 2 CTCAE version 4.03 thrombocytopenia. Eight pts (32%) developed grade 2-3 CTCAE version 4.03 dry skin or rash, 2 pts (8%) grade 2 CTCAE version 4.03 nausea-vomiting. Conclusions: Panitumumab has minimal benefit in pts with KRAS WT MCRC who have progressed on prior cetuximab andthis approach up to date should not be adopted in the clinical practice. Our data anyway show a longer PFS and OS as compared to other few series in the same setting. Further confirmatory prospective studies with larger series of pts would be necessary.
Prognostic value of incidental betablockers use in metastatic colorectal cancer patients receiving first-line treatment.
Authors: Del Prete Michela , Giampieri Riccardo , Scartozzi Mario , Maccaroni Elena , Faloppi Luca , Bianconi Maristella , Bittoni Alessandro , Cecchini Luca , Cascinu Stefano 
Published: March 2020

e14610 Background: Preclinical and retrospective studies suggested antitumor activity for the incidental use of betablockers in various tumour types. Data regarding colorectal cancer are lacking. We assessed the correlation between the incidental use of betablockers and clinical outcome in colorectal cancer patients receiving first-line therapy. Methods: 235 patients treated with first-line chemotherapy alone (128 patients) and with Bevacizumab (107 patients) were analysed. Patients were stratified for betablockers use, age, sex, site of metastases, previous adjuvant chemotherapy and ECOG performance status. Results: 29 patients (12%) were on treatment with betablockers at the time of first-line therapy: 20 (16%) in the chemotherapy alone group and 9 in the bevacizumab group (8%). In both groups patients receiving or not betablockers were similar for all main clinical characteristics. In the chemotherapy alone group, patients receiving betablockers showed an improved response rate (60% vs. 33%, p=0.044) and overall survival (mOS 41.3 vs 25.7 months, p=0.03, HR:2.26, 95% CI: 1.05-3.24). Only a trend for improved progression free survival was noticed. In the 107 patients receiving chemotherapy with bevacizumab a trend towards a worse overall survival was seen for patients receiving betablockers, although this was not statistically significant (mOS 16 vs 23.7 months, p=0.26, HR:0.64, 95% CI: 0.22-1.49). No significant differences were seen in regards of progression free survival or different response rate patterns between the two groups. Conclusions: Our analysis confirms a potential prognostic role for the use of betablockers in colorectal cancer patients treated with chemotherapy. Our findings are in line with preclinical studies suggesting that beta-adrenergic signalling may regulate cancerogenesis and tumor invasiveness. Our analysis suggests a potential worse outcome for patients on betablockers receiving Bevacizumab-based treatment, although the small number of patients precludes any definitive conclusion. We suggest that in future prospective trials the incidental use of betablockers will be considered a stratification factor for clinical outcome.
Addition of bevacizumab to compensate for the negative influence of attenuated relative dose intensity of cytotoxic agents on the outcome in patients with metastatic colorectal cancer.
Authors: Nakayama Goro , Hayashi Naomi , Tanaka Chie , Fujii Tsutomu , Ando Yuichi , Kodera Yasuhiro 
Published: March 2020

e14614 Background: We reported that relative dose intensity (RDI) of key cytotoxic agents, irinotecan (IRI) and oxaliplatin (OX), is a significant predictor of disease control in patients with metastatic colorectal cancer (mCRC). However, in concomitant therapy with bevacizumab (BEV), the influence of adding BEV on the relation between RDI of cytotoxic agents and outcomes are unclear. In this study, we evaluate the impact of BEV on RDI of IRI and OX-based chemotherapy on the outcome of mCRC. Methods: A retrospective analysis of mCRC patients entered into three prospective clinical trials, testing FOLFIRI (CCOG-0502), mFOLFOX6 (CCOG-0704), FOLFIRI plus BEV and mFOLFOX6 plus BEV (CCOG-0801), was performed. RDI was calculated as the delivered dose intensity divided by standard dose intensity calculated for each regimen and compared to response rate (RR), disease control rate (DCR) and progression-free survival (PFS). Results: In FOLFIRI therapy, higher RDI (IRI, >median: 80%) group achieved significant better RR, DCR and PFS than lower RDI (<median) group (RR: 65 vs. 6% [p=0.001], DCR: 100 vs. 41% [p=0.003] and PFS: 9.9 vs. 5.6 months [p=0.002]). The other hand, in FOLFIRI plus BEV therapy, there were no difference between higher and lower RDI (IRI, median: 76%) group in ORR, DCR and PFS (RR: 31 vs. 27% [p=0.779], DCR: 75 vs. 53% [p=0.208] and PFS: 6.2 vs. 7.3 months [p=0.903]). In mFOLFOX6 therapy, higher RDI (OX, >median: 79%) group achieved better disease control than lower RDI group (RR: 47 vs. 33% [p=0.456], DCR: 100 vs. 73% [p=0.032] and PFS: 8.5 vs. 6.2 months [p=0.064]). In addition of BEV, there were no difference between higher and lower RDI (OX, median: 76%) group in any outcomes (RR: 54 vs. 74% [p=0.159], DCR: 88 vs. 91% [p=0.672] and PFS: 11.6 vs. 11.7 months [p=0.797]). Conclusions: RDI of key cytotoxic agents is a significant predictor of disease control, especially in IRI-based regimen. Nevertheless, in concomitant therapy with BEV, there were no relations between RDI of cytotoxic agents and outcomes. These results suggest that BEV could have ‘covering effect’ to reduce the influence of dose modification of cytotoxic agents in mCRC patients.
Metformin and biomarkers relevant to neoplasia in nondiabetic patients.
Authors: Pollak Michael N. , Blouin Marie-Jose , Vasilevsky Carol-Ann , Cefis Luca , Frank Russell , Tao Yuzhen , Li Zhen , Tu Yinggang , Wang Ye , Zakikhani Mahvash , Trifiro Mark , Schwab Matthias 
Published: March 2020

e14615 Background: Use of the anti-diabetic drug Metformin has been associated with reduced risk or improved prognosis of several cancers in both lab models and retrospective population studies of diabetics. Plausible mechanisms of action include (1) reduction in serum levels of insulin or inflammatory cytokines and (2) direct effects on target cells due to action of the drug as an inhibitor of mitochondrial respiration, including activation of AMPK. Methods: Non-diabetic subjects (n = 47) consented to bloodwork and sigmoid biopsy at screening colonoscopy, metformin administration (500 mg TID) for 10 weeks, and end-of-study sigmoid biopsy and bloodwork. Serum assays were performed on both fasting and post standard oral glucose load specimens. Metformin levels were measured by mass spectroscopy. Anti-phospho-histone-3 immunostaining was used to quantify proliferation. Results: Metformin reduced fasting levels of c-peptide, insulin, and IL-6 levels by < 10%, a magnitude of change that laboratory studies suggest is unlikely to be biologically significant. However, postprandial insulin levels following metformin were reduced by 18 % relative to baseline postprandial levels, a finding of potential physiologic relevance. Serum metformin level showed considerable variation between subjects (1005 ± 769 ng/ml) and this variation was not correlated with effects of metformin on epithelial proliferation. Proliferation index fell from 5.9 to 3.3, (p<0.03), a change greater than predicted by in vitro studies of direct action of metformin at the concentrations measured in serum. Conclusions: Metformin lowers insulin levels even in non-diabetic subjects, and post prandial insulin levels are more sensitive indicators of metformin action than fasting biomarkers. As high insulin level has been linked to increased cancer risk and/or worse prognosis (eg J Natl Cancer Inst. 2004;96:546), this systemic action suggests clinical applications. However, direct exposure of colonic epithelial cells to high luminal concentrations of metformin may also be relevant and is one of several factors that may explain the greater inhibitory effect of the drug on colonic epithelium proliferation than that previously reported for breast or prostate.
Patterns of care of elderly patients with metastatic colorectal cancer.
Authors: Parakh Sagun , Ali Sayed Sahanawaz , Wong Hui-li , Field Kathryn M , Shapiro Jeremy David , Nott Louise M. , McKendrick Joseph James , Gibbs Peter , Yip Desmond 
Published: March 2020

e14640 Background: Elderly patients (pts) account for a large proportion of pts with metastatic colorectal cancer (mCRC). Despite this they are underrepresented in clinical trials and often undertreated. The purpose of this study is to review the patterns of care of elderly pts with mCRC in the community setting. Methods: Retrospective analysis of 507 elderly (age ≥ 65 years (yrs)) pts with mCRC on the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database enrolled between July 2009 and November 2012. Comprehensive clinical data was collected prospectively on pts with mCRC from 14 sites across Australia. In this analysis pts were grouped according to age: 65-75, 75-85 and ≥85 yrs. Treatment patterns and intent, performance status (PS), and overall survival (OS) were analysed by age cohorts. Kaplan-Meier method was used for survival analysis. Results: In this cohort, 213 (42.0%), 216 (42.6%) and 78 (15.4%) pts were aged 65-75, 75-85 and >85 yrs respectively. Older patients were more likely to be female (30.5% vs 42.1% vs 52.6%, p=0.0012) and have worse PS (PS≥2: 18.3% vs 25.9% vs 48.7%, p<0.0001). There were no differences in comorbidity score, primary tumour site or resection rates between age groups. In total, 358 (70.6%) elderly pts received chemotherapy. However, chemotherapy use declined significantly with increasing age (83.1% vs 70.8% vs 35.9%, p<0.0001). Among the very elderly (≥85 yrs) pts who received chemotherapy (n=28), 12 (42.9%) received combination chemotherapy and 6 (21.4%) were given bevacizumab. Median OS was 24.3, 17.7 and 11.3 months in the 65-75, 75-85 and >85 yrs age groups respectively (p<0.0001). Pts receiving chemotherapy had significantly longer OS than those who did not (median OS 22.7 vs 6.4 months, HR 0.28 (95% CI 0.21-0.38, p<0.0001)). Conclusions: This is the largest series of elderly pts with mCRC in Australia. Multiple studies have confirmed the safety and efficacy of fluorouracil and bevacizumab but in our cohort, chemotherapy and bevacizumab appear to be underutilised in the elderly. Chart review is planned to explore reasons for not administering chemotherapy.
Chemotherapy-induced diarrhea in older patients with colorectal cancer receiving fluoropyrimidines: A retrospective review.
Authors: Iyer Laxmi H , Browner Ilene S. , Blackford Amanda L. , Laheru Daniel A. , Azad Nilofer Saba , Diaz Luis A. , Donehower Ross C. , Purtell Michael J. , Zheng Lei , Le Dung T. , Cosgrove David , Rasheed Zeshaan , Kadan Maura , De Jesus-Acosta Ana 
Published: March 2020

e14647 Background: Chemotherapy-induced diarrhea (CID) is a common treatment-limiting toxicity of regimens used for colorectal cancer (CRC). Fluoropyrimidines, the backbone of CRC regimens, are associated with diarrhea, but the frequency and severity in older patients are less known due to under-representation of older patients in CRC trials. As life expectancy increases, the prevalence of older CRC patients will increase. We aimed to evaluate if older patients are vulnerable to CID. Methods: We retrospectively studied patients >70 years old who received fluoropyrimidines based therapy for stages II-IV CRC at Johns Hopkins and Bayview Medical Center from 1996-2007. Patient demographics and cancer-specific data were retrieved. Diarrhea was graded per National Cancer Institute Clinical Toxicity Criteria. Results: We included 150 patients > 70 years old. Median age was 75 (range 70-87). 65 (43%) were 70-74 years old, 52 (35%) were 75-79 years and 33 (22%) > 80. Diarrhea occurred in 48% (n=72) of patients. Presence of diarrhea was not significantly associated with increasing age (70-74, 75-79 or >80 years), gender, ECOG performance, number of comorbidities or medications. Severe grade 3-4 diarrhea occurred in 16% (n=24) and was associated with advanced stage (p=0.04). CID (all grades) was more common in cycle 1 than subsequent cycles (p=0.002). Conclusions: Fluoropyrimidines based therapy was tolerated in older patients with CRC. Incidence of CID was not associated with increasing age, gender, performance, comorbidities or polypharmacy. Severe diarrhea occurs in advanced stage and early during therapy. Larger prospective studies are needed to definitively evaluate the impact of age on CID.
Retrospective analysis of 178 patients with stage I rectum cancer.
Authors: Cihan Sener , Ozdemir Nuriye , Urakci Zuhat , Kucukoner Mehmet , Dane Faysal , Yazilitas Dogan , Durnali Ayse , Yuksel Sinemis , Colak Dilsen , Seker Metin , Taskoylu Burcu , Aksahin Arzu , Ozturk Banu , Demirci Umut , Turan Nedim , Aksoy Sercan , Atasoy Ajlan 
Published: March 2020

e14662 Background: There is no strong evidence to suggest that type of adjuvant therapy has any role in the management of stage I rectum cancer. The risks of local relapse and distant metastasis are higher in rectal cancer than colon cancer. Due to the more aggressive nature of rectal cancers, we explored the clinical and pathologic factors that could predict the risk of relapse in stage I disease. Methods: This multicenter study was carried out by Anatolian Society of Medical Oncology. 178 patients with rectal cancers who underwent curative surgery between 1994 and 2012 were included. Retrospective analyses were made using data collected from medical records. Results: The median age was 58 years (26-85). Low anterior resection (LAR) was the most preferred surgical method. Most tumors were well or moderately differentiated. After surgery, 13 patients (7.3%) received radiotherapy alone, 12 patients (6.7%) received chemotherapy alone and 15 patients (8.4%) were given chemoradiotherapy. Median follow-up was 29 months (3-225). 41 patients (23%) had relapse; relapses were local in 18 patients (10.1%) and distant in 12 patients (6.7%). 11 patients (6.2%) who had no relapse data were considered to be disease free. The 3-year disease free survival (DFS) was 74% and the overall survival (OS) was 94%. Mucinous histology and adjuvant therapy were found to have statistically insignificant correlations with relapse and survival. Conclusions: There is no strong evidence to support the role of any type of adjuvant therapy after resection in stage I rectal cancer. Approximately ¼ of patients had local or systemic relapse. This is a high rate for stage I tumors. The rates of relapse were slightly higher in the patients who had no adjuvant therapy and those who had mucinous tumors. There may be a role for adjuvant therapy in high-risk stage I rectal tumors. However, there is still a need for prospective studies in this regard. [Table: see text]
Outcomes of oxaliplatin-based adjuvant chemotherapy in pathologically lymph node positive (ypN+) rectal cancer.
Authors: Al Zahrani Ahmad , Brierley James D. , Kennedy Erin Diane , Krzyzanowska Monika 
Published: March 2020

e14664 Background: Standard therapy for locally advanced rectal cancer( LARC) with pre-operative chemoradiation(CRT) followed by curative surgery and adjuvant 5-flourouracil (5-FU) has resulted in a 5-year local relapse (LR) rate of less than 10% and incidence of distant metastases of about 36%. Accumulating data suggests that pathological lymph node status post CRT (ypN) is a major prognostic factor for long term outcomes in LARC .The role of adjuvant oxaliplatin-based therapy has not yet been well defined in ypN+ patients and is the focus of this study. Methods: Patients with ypN+ rectal cancer who underwent fluoropyrimidine-based preoperative CRT followed by curative surgery and received adjuvant oxaliplatin- (group 1) or fluoropyrimidine-based (group 2) chemotherapy at Princess Margaret Hospital were retrospectively reviewed.The study end point was comparison of three year disease free survival(DFS) and freedom from distant metastasis (FDM) in group 1 vs 2 using log-rank test. Results: Between 2003 and 2010, 25 pts in group 1 (adjuvant FOLFOX, n=23 and FOLFOX/bevacizumab, n=2) and 38 pts in group 2 ( adjuvant 5-FU/LV, n =37; capecitabine, n=1) were reviewed. Baseline characteristics were similar in both groups except more pts in group 2 had < 12 lymph nodes (LNs) retrieved (p=0.02), whereas more pts in group 1 were female (p=0.03)and had ypN2 vs ypN1 (p=0.01). Median follow-up was 33 months in group 1 and 38 months in group 2 (range: 3-86). Median age: 58 years. Male: 51, 80%. Five pts (8%) in the entire cohort experienced LR and 20 pts (31.7%) had distant metastasis. A trend toward better three-year DFS was observed in favour of oxaliplatin-based therapy (76% in group 1 vs. 51% in group 2; HR=0.4, 95%CI = 0.1-1.0; P=0.05). Corresponding three-year FDM rates were 83% and 58%, respectively (HR=0.23; 95% CI = 0.6-0.8; p= 0.01). In multivariate analysis, number of LNs retrieved of ≥12 and adjuvant oxaliplatin-based therapy were independent prognostic factors for improved DFS and FDM, respectively. Conclusions: Our analysis suggests that in ypN+ rectal cancer, addition of oxaliplatin to adjuvant therapy is associated with better outcomes. A prospective confirmatory randomized trial would be informative.