bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and patterns of phospho insulin growth factor receptor-1 (pIGF-1R) and matrilysin (MMP7) expression in metastatic colorectal cancer (mCRC), and correlation with KRAS status: A prospective evaluation in the PULSE trial—A GEMCAD study.
Authors: Alonso Vicente , Fernandez-Martos Carlos , Martin Marta , Salud Antonieta , Mendez Jose Carlos , Pericay Carles , Manzano Hermini , Gallego Javier , Horndler Carlos , Machado Isidro , Tobeña Maria , Garcia-Albeniz Xabier , Rubini Michele , Jares Pedro , Cuatrecasas Miriam , Maurel Joan 
Published: March 2020

e14041 Background: MMP7 can activate IGF-1R by IGF release due to IGFBP degradation. Activation of IGF-1R can contribute to EGFR resistance by transactivation. We previously described that concomitant expression of p-IGF-1R and MMP7 (Double positive; DP), correlates with poor prognosis, in KRAS WT patients (pts) treated with anti-EGFR compounds (Horndler el al, 2011). Therefore we designed a prospective clinical trial to validate DP as a marker of resistance in KRAS WT pts treated in first-line therapy with FOLFOX-6 plus panitumumab. Methods: mCRC pts in the ongoing prospective PULSE trial (NCT0128833) were prospectively evaluated for p-IGF-1R (p-1316), MMP7 expression and KRAS mutational status. Pts defined as DP should express MMP7 (++ or +++ intensity in >66% of tumor cells) and p-IGF-1R (++ or +++ intensity in >66% of tumor cells). KRAS pts with mutations at exon 2 were excluded. The study was designed to include 40 pts in the two groups (DP vs non-DP) to detect a Hazard ratio difference in PFS of <0.5 (DP vs non-DP) with 80% power. Results: From November 2010 to December 2011, 113 consecutive pts were screened from 24 Spanish Institutions. 54 KRAS WT (40 pts non-DP and 14 DP) have been included. The non-DP arm has being recently closed for inclusion, due to pre-planned complete accrual. Among DP pts, 27% were KRAS WT and 30% KRAS mutant; p=0.63. 48% of cases were positive for p-IGF-1R. Phospho-IGF-1R positive cases had different patterns of staining: peri-nuclear in 76%, 11% nuclear and only 13% membrane-apical staining. These patterns do not differ between KRAS WT; (n=70) and KRAS mutant pts (n=43) (p=0.60). Tumors with positive p-IGF-1R expression, independently of the pattern, have higher MMP7 co-expression (59%) compared with negative cases (13%) (p<0.0001). Conclusions: MMP7 contributes to activate IGF-1R pathway in pts with mCRC. Internalization of the activated IGF-1R, could explain in part, the lack of efficacy of IGF-1R inhibitors in mCRC clinical trials.
Preoperative chemoradiation with nimotuzumab and capecitabine in patients with locally advanced rectal cancer: A phase II study.
Authors: Zhu Yuan , Liu Luying , Luo Jialing , Li Dechuan , Zhu Yuping 
Published: March 2020

e14049 Background: To evaluate the efficacy and safety of preoperative chemoradiation with Nimotuzumab(a humanized monoclonal antibody that targets and binds to the epidermal growth factor receptor)and capecitabine in the patients with locally advanced rectal cancer. Methods: Twelve patients with locally advanced, nonmetastatic, and mid- to lower rectal cancer were enrolled. Radiotherapy was delivered at a dose of 50 Gy/25 fractions. Concurrent therapy consisted of Nimotuzumab 400 mg/m2,1 week before radiotherapy, and then Nimotuzumab 400 mg/m2/week for 5 weeks, and capecitabine 1,650 mg/m2/day for 5 days a week (weekdays only) from the first day during radiotherapy. Three weeks after the end of chemoradiation, 1 cycle chemotherapy with oxaliplatin and capecitabine(XELOX) was performed. Oxaliplatin 130mg/m2, Day1 and capecitabine 1000 mg/m2, bid, from Day 1 to Day 14. Postoperative chemotherapy after surgery followed by preoperative CRT was in all patients, The same dosage of XELOX was started within 3 to 4 weeks after surgery, repeated every 3 weeks for 6 cycles. Total mesorectal excision was performed within 6 ~ 8 weeks. The pathologic response was evaluated as study endpoint, and an additional KRAS mutation analysis was performed. Results: In total, 9 patients completed their planned preoperative chemoradiation and underwent R0 resection. The pathologic complete response rate was 33.3% (3/9), and 3 patients (33.3%) showed near total regression of tumor. Grade 3 toxicities was diarrhea (2/12, 16.7 %), No grade 4 toxicity was observed. KRAS mutations were found in 2 of 12 patients (16.7%) who had available tissue for testing. Clinical outcomes were not significantly correlated with KRAS mutation status. Conclusions: Preoperative chemoradiation with Nimotuzumab and capecitabine was active and well tolerated. KRAS mutation status was not a predictive factor for pathologic response in this study.
Colorectal cancer in young population: Yangon, Myanmar.
Authors: Nwe Khin Khin 
Published: March 2020

e14055 Background: CRC is the tenth most common cause of cancer in 2006 Myanmar Cancer Statistic. Recently, increased incidence of CRC among young age has been seen in our population. Methods: Demographic data of CRC pts registered in medical oncology unit, YGH from January 2009 to September, 2011 were studied. Age under 40 yrs was considered as a young patient. Stage distribution were analyzed to study about young onset CRC pattern. Results: Among 351 CRC patients registered, 120pts (34.19%) were under 40 yrs old. In young age group, age range from 12 to 40 yrs (median 29.5 yrs). Male to female ration was 1:1.26. Left-sided cancer (splenic flexure to rectum) in 93 patients (77.5%) and right sided (caecum to transverse colon) cancer in 27 pts (22.5%). Six pts (5%) were stage I, 41 people (34.17%) with stage II. Forty-four patients (36.67%) were node positive Stage III and 29 people (24.17%) with distant metastasis, Stage IV. Conclusions: Three percent of colorectal cancers occur in patients younger than 40 years of age in World Cancer Data. However, one third of CRC pts registered within 3 yrs in our unit were under age 40.The commonest stage seen in those pts were stage III at initial diagnosed. According to this data, younger onset of CRC in Myanmar is increasing although it doesn’t reflect the whole population. Further larger study is required to prove it. [Table: see text]
Adverse events (AE) following diagnosis (Dx) in older metastatic colorectal cancer (mCRC) patients (Pts).
Authors: Shankaran Veena , Mummy David G , Blough David K , Koepl Lisel , Yim Yeun Mi , Yu Elaine , Ramsey Scott David 
Published: March 2020

e14068 Background: The relative safety of newer drugs in older pts with mCRC is understudied. The objective of this analysis is to determine factors associated with AEs in a population-based sample of older mCRC pts treated in real-world clinical settings. Methods: Pts ≥ age 65 Dx with mCRC in 2004-2007 were identified from SEER-Medicare, and excluded if they were enrolled in a Medicare HMO or lacked Medicare parts A and B. Pts who received 1st line (1L) chemotherapy (CTx) within 3 mo of Dx were dichotomized as 1L CTx alone and 1L CTx + bevacizumab (BV). Preexisting conditions (PCs) identified from claims in the 12 mo prior to start of 1L CTx were grouped into 5 categories (cardiovascular (CV), cerebrovascular (CNS), gastrointestinal (GI), tissue integrity (TI), and pulmonary (Pulm)). Claims for any of these same conditions between start of 1L CTx and end of follow-up were identified as AEs. Crude AE incidence rates were determined. Logistic regression was used to examine factors associated with BV use. Factors associated with time to 1st AE were identified in a Cox model. Results: 4,514 pts (median age 77) met inclusion, of whom 1,139 (25%) received 1L CTx only and 669 (15%) received 1L CTx + BV. BV use was less likely among pts age ≥ 75 (OR 0.35, p<0.001), non-whites (OR 0.75, p=0.002), and women (OR 0.8, p=0.001). Bev use was as likely in pts with CV, Pulm, or CNS PCs, and more likely in pts with GI (OR 1.67, p <0.001) and TI (OR 2.75, p=0.001) PCs. In a Cox model of time to 1st AE with death as a competing risk, increased risk of AE was associated with age ≥ 75 (HR 1.13, p=0.02), CNS PC (HR 1.35, p=0.02), and CV PC (HR 1.13, p=0.05). Relative to 1L CTx alone, pts receiving 1L CTx + BV did not have a higher AE risk (HR 0.89, 95% CI 0.80-0.99). AE incidence was higher in pts receiving 1L CTx alone (without subsequent biologic) (185 events / 100,000 person-days (P-D) compared with pts receiving 1L CTx + BV (139 events / 100,000 P-D). Conclusions: In this cohort, pts who received 1L CTx + BV had neither increased AE incidence nor increased risk of 1st AE compared to pts who received 1L CTx alone. PCs were not associated with decreased BV use. These data suggests BV utilization may not increase AE risk among elderly mCRC pts tx in the community.
Molecular predictors of treatment response in colon and gastric cancer.
Authors: Shen John P. , Roeland Eric , Hwang Michael , Shimabukuro Kelly Anne , Sicklick Jason Keith , Ramamoorthy Sonia , McLemore Elisabeth C. , Reid Tony R. , Lowy Andrew M. , Fanta Paul Timothy 
Published: March 2020

e14069 Background: With the exception of KRAS mutational status, there is limited use of tumor-derived biomarkers in the clinical management of GI malignancies. High ERCC1 expression is associated with inferior outcomes in platinum-exposed patients with non-small cell lung, esophageal, and head and neck cancers. Previous studies have concluded ERCC-1 gene expression levels may identify patients unlikely to benefit from oxaliplatin-based chemotherapy in metastatic colon cancer and in the adjuvant therapy of esophageal/gastric cancer. Methods: Biomarkers were obtained from formalin fixed paraffin embedded tumor samples from 69 colorectal and 22 gastric cancer subjects. Each tumor was dissected using laser-captured microdissection and analyzed mRNA expression using a quantitative RT-PCR. A retrospective chart review was performed to evaluate clinical response. The primary objective was todetermine the prevalence of select tumor biomarkers including ERCC1, TS, VEGFR2a, Her2, KRAS, BRAF, and EGFR mutation status and and correlate these with overall survival. Results: Colon: Subjects with high ERCC1 expression had significantly worse OS survival compared to those with lower ERCC1 expression (26.0 vs 71.1 mo, p=0.0077). There was a trend towards decreased OS with high TS expression, but this was not statistically significant (71 vs 56 mo, p=0.49). Subjects with the V600E BRAF mutation had significantly worse OS compared to wild-type tumors (48.5 vs 61.3 mo, p=0.03). Gastric: Median OS was not reached due to a limited number of gastric subjects and only 9 of 22 had died at time of analysis. Updated analysis is planned. Conclusions: Even in this small population it is possible to detect survival differences using biomarker analysis of biopsy and resection specimens. Virtually all tumor samples yielded sufficient material for analyses. We suspect that the decreased OS in high ERCC1 expressing tumors is a result of platinum resistance. These results suggest that the use of biomarkers may identify patients unlikely to respond to conventional therapy, and warrant further investigation in a prospective clinical trial.
Predictors of pathologic complete response (pCR) after neoadjuvant chemoradiation (Neo CRT) for rectal cancer: A multicenter population-based study.
Authors: Armstrong Dawn Elizabeth , Ali Haider , Powell Erin Diana , Price Hiller Julie A. , Tang Patricia , Bebb D. Gwyn , Dowden Scot D. , Tam Vincent Channing , Lupichuk Sasha M. , MacLean Anthony , Easaw Jacob C. , Davies Janine Marie , Heng Daniel Yick Chin , Vickers Michael M. 
Published: March 2020

e14073 Background: pCR to Neo CRT for rectal cancer is associated with better outcomes and used as an early indicator of response. To assess the rate and predictors of pCR, as well as access to care, we performed a retrospective study in two Canadian provinces. Methods: Cancer registries identified consecutive patients with clinical stage I-III rectal cancer from the Tom Baker Cancer Center, Cross Cancer Institute, and Dr. H. Bliss Murphy Cancer Centre who received Neo CRT and had curative intent surgery (Sx) from 2005 to 2011. Patient, tumor and therapy characteristics were correlated with response. Results: 301 patients were included of which 59 (19.6%) had a pCR to Neo CRT. At a median follow-up of 17 months, disease free survival was 96.7% for pCR vs 82.3% for non-pCR (p=0.005). 43 (73%) patients with pCR received adjuvant chemotherapy including bolus FU 27 (63%), capecitabine 10 (23%) and oxaliplatin-based 6 (14%). Median time from diagnosis to consult was 4 weeks (wks), from consult to start of Neo CRT 3.3 wks and start of CRT to Sx 13 wks. On multivariate analysis a low pre-op CEA (p=0.0323) was a significant independent predictor of pCR while statin use at initial consult (p=0.077) and higher pre-op hemoglobin (p=0.0974) trended toward significance when adjusted for clinical stage. Conclusions: Rates of pCR in a population based setting are substantial. A lower pre-op CEA is associated with a pCR to Neo CRT. Statin use and pre-op hemoglobin require further investigation. Our access to care data provides a baseline for future comparisons. [Table: see text]
Heterogeneous prevalence of somatic mutations in KRAS, BRAF, and PIK3CA genes among patients with colorectal carcinoma: Clues from Sardinia.
Authors: Palomba Grazia , Colombino Maria , Contu Antonio Silverio , Massidda Bruno , Baldino Giovanni , Pazzola Antonio , Ionta Maria Teresa , Capelli Francesca , Trova Vittorio , Sedda Tito , Tanda Francesco , Palmieri Giuseppe , Cossu Antonio ,   Sardinian Translational Oncology Group (STOG)
Published: March 2020

e14094 Background: Role of KRAS, BRAF and PIK3CA mutations in pathogenesis of colorectal cancer (CRC) has been mostly clarified. In this population-based study, we investigated the incidence rates and roles for such somatic mutations in genetically isolated population of Sardinia. Methods: From April 2009 to July 2011, formalin-fixed paraffin-embedded tissues (n=478) were prospectively collected from Sardinian CRC patients at clinics across the entire island. Genomic DNA was isolated from tissue sections and screened for mutations in KRAS, BRAF, and PIK3CA genes by automated DNA sequencing. Results: Overall, KRAS tumor mutation rate was 30% (145/478 positive cases). Distribution of mutation carriers was however different within the island: 87/204 (43%) in North Sardinia vs. 58/274 (21%) in Middle-South Sardinia (p=0.023). Among 384 CRC cases whose DNA was available, only one (0.3%) mutation in BRAF gene was observed; conversely, PIK3CA was found mutated in 158/384 (41%) patients. An inverse distribution of PIK3CA mutation rates was observed within Sardinian population: 60/181 (33%) cases from northern vs. 98/203 (48%) cases from central-southern island. This heterogeneity in frequencies of KRAS/PIK3CA somatic mutations is consistent with already-reported discrepancies in distribution of germline mutations for other malignancies within Sardinian population. Preliminary clinical evaluation of 118 KRAS wild-type patients undergoing anti-EGFR-based treatment indicated lack of role for PIK3CA in predicting response to therapy in our series. Conclusions: Our findings further support the hypothesis that patients’ origin and genetic background may contribute to even determine the incidence rate of somatic mutations in candidate cancer genes.
Activity of neoadjuvant bevacizumab at the time of surgery after 6 weeks of preoperative cessation: A translational study.
Authors: Starlinger Patrick , Alidzanovic Lejla , Schauer Dominic , Maier Thomas , Sommerfeldt Silvia , Perisanidis Beata , Tamandl Dietmar , Gruenberger Birgit , Gruenberger Thomas , Brostjan Christine 
Published: March 2020

e14099 Background: The use of bevacizumab (BV), a monoclonal antibody against VEGF, together with an increase in hepatic resection has improved the outcome of colorectal cancer (CRC) patients with liver metastasis. However, despite the frequent use of BV, its accurate timing prior to liver resection to avoid surgical complications and to allow for hepatic regeneration remains discussed controversially. In this context, it is unclear to which extent VEGF is complexed by BV at the time of surgery. Methods: 42 CRC patients with liver metastases, potentially curable by resection, were included. Patients received neoadjuvant chemotherapy (CTx) either with or without concomitant biweekly BV. The last cycle of therapy did not include BV, resulting in a median 6 weeks between the last administration of BV and surgery. Plasma and wound fluid were obtained perioperatively. Immunoprecipitation was applied to determine the proportion of BV-bound VEGF. Alternative angiogenesis factors were evaluated. Results: No increased perioperative complications in BV treated patients were observed. At the time of surgery, the majority of plasma VEGF was inactivated by BV. In wound fluid, the actual site of wound healing and hepatic regeneration, VEGF was remarkably low and also complexed by BV. The anti-angiogenic protein thrombospondin-1 was reduced in BV treated patients. Conclusions: These data document that after the clinical standard cessation time of 6 weeks, BV is still fully active and binds to the majority of circulating and local (wound fluid) VEGF. Despite the potent VEGF inactivation at the time of liver resection no substantial increase in perioperative morbidity after neoadjuvant BV therapy has been documented in our study and the current literature. Compensatory mechanisms, such as thrombospondin-1 reduction during BV treatment may enable wound healing.
Neoadjuvant capecitabine and oxaliplatin (CAPOX) followed by chemoradiation (CRT) in high-risk rectal cancer: A single-institution experience.
Authors: Ahmad Saif , Parashar Deepak , Jephcott Catherine Rachel , Ford Hugo , Wilson Charles 
Published: March 2020

e14100 Background: Total Mesorectal Excision (TME) is standard of care in early rectal cancer. Pre-operative CRT facilitates microscopic complete resection (R0), improving outcome in high risk disease. Recent Phase 2 studies investigated the role of neoadjuvant CAPOX chemotherapy pre-CRT with promising results. We have adopted this strategy in high risk cancers with threatened circumferential resection margin (CRM) on MRI, and report our institution’s early outcome data. Methods: Retrospective data was collected on 37 patients with high risk disease treated March 2007 to December 2011. Patients received 12 weeks oxaliplatin (130mg/m2) and capecitabine (1000mg/m2 BD for 14 days) every 3 weeks, followed by CRT (45 Gy/ 25 #) with concurrent capecitabine (800mg/m2 BD). 11/37 patients had a 5.4 Gy/ 3 # boost with CRT. 4 patients were in a clinical trial, 2 of whom had cetuximab in addition to CAPOX. Patients deemed operable on repeat MRI had TME and 4 cycles of adjuvant CAPOX. Results: Median age was 64 (33-78) and male: female ratio 2.1:1. Median follow-up was 22 months (1.9-53.7). 2 patients did not complete 4 cycles neoadjuvant CAPOX due to toxicity. Median time to surgery post CRT was 6.6 weeks (4.7-10 weeks). 1 patient had an embolic event and femoral embolectomy. 7/31 (23%) patients had no post-operative chemotherapy (4 wound; 2 previous toxicity; 1 comorbidity). Radiological response rates post CRT were 26/34 (76%). 2 patients progressed and were unable to have radical surgery. 1 further patient was found to have unsuspected metastatic disease (liver) at time of surgery. 28/35 (80%) patients had R0 resection and pathological complete response (pCR) was 6/37 (16%). 2 year DFS and OS was 89% and 91.3%. Conclusions: Our outcomes, within an unselected cohort, reflect outcomes consistent with published trial data and support routine use of pre-operative CAPOX and CRT in high risk rectal cancers. This strategy is feasible in a non-trial population, and offers the benefit of early sterilisation of micrometastases, better prediction of chemotherapy response and facilitates the incorporation of novel agents within neoadjuvant window studies.
Capecitabine in early-stage colon cancer and metastatic colorectal cancer: Results from an Austrian noninterventional trial.
Authors: Eisterer Wolfgang , Jagdt Bjoern , Haeusler Christa , Krenn Markus 
Published: March 2020

e14103 Background: Capecitabine (Cap) is approved for adjuvant therapy in stage III colon cancer and for metastatic colorectal cancer (mCRC) in Austria. Methods: In this open-label, multicenter, single-arm non-interventional trial, Cap-based therapy in patients with early-stage colon cancer and mCRC was observed at 30 sites. Cap was prescribed at the physician’s discretion and according to drug labelling. 409 patients were included between 2008 and 2011. Safety of Cap in routine clinical practice was the primary study endpoint. All adverse events (AEs) were documented in an online CRF by participating investigators. Progression-free survival (PFS), defined as the time from study entry until tumour progression or death, and treatment duration were also assessed. Results: Most of the 409 patients were ≥65 years old (72.6%; n=297). 249 (60.9%) patients were male and 160 (39.1%) were female. 221 (54.0%) patients received Cap as adjuvant therapy; 111 (50.2%) of these received Cap alone, and 110 (49.8%) were treated with Cap plus oxaliplatin. 188 (46.0%) patients were treated for mCRC; 105 (55.9%) received first-line therapy, 48 (25.5%) second-line therapy and 35 (18.6%) third-line or later lines of therapy with different Cap-containing regimens. 163 mCRC patients were eligible for PFS evaluation. The median PFS was 8.1 (range 1.0–28.5) months. Patients who received Cap-based therapy for at least 8 cycles (n=97) had a profound increase in PFS to 9.4 months. The longest treatment duration with Cap was 47 cycles. The median duration of treatment for all patients was 8 cycles (range 1–47) at a median daily dose of 1944 mg/m2 (range 833–3055 mg/m²) for Cap alone and 1862 mg/m2 (range 1111–4166 mg/m²) as part of a combination regimen. The most common grade 3/4 AEs included diarrhoea (2.2%), hand-foot syndrome (2.0%), nausea (0.7%), neuropathy (0.7%), and leukopenia (0.2%). Conclusions: Cap therapy is well tolerated in routine clinical practice. The median number of 8 cycles correlates well with the suggested treatment duration. AEs included only known and previously documented safety reactions. Prolonged treatment with Cap in patients with mCRC leads to a meaningful increase in PFS.
Role of estrogen receptor-β as prognostic factor in colorectal cancer.
Authors: Alonso Lorenzo , Pérez-Ruiz Elisabeth , Perez-Villa L. , Sevilla Isabel , Torres Esperanza , de Luque V. , Alvarez Martina , Vicioso Luis , Alba E. 
Published: March 2020

e14115 Background: Gender-related differences in colorectal cancer (CRC) development have been reported with a higher incidence in males than in females and several studies suggest estrogens can be protective. The role of these receptors is controversial. The aim was to elucidate the association between estrogen receptor- β (ER- β), clinicopathological variables, disease-free survival (DFS), and overall survival (OS). Methods: Protein expression was evaluated by immunohistochemistry, and antibody staining detected in the nuclear compartment was taken into account in 109 CRC patients tissue. Results: The sample characteristics are summarized in Table 1. The expression of nuclear ERβ was found to be positive in 101 cases (92.7%), and only 8 cases (7.3%) were negative. The ERβ expression was found to be associated with mucinous histology (p<0.0001), while no association was found with any of the remaining variables examined. There was a non significant association between ERβ and IIIB-IV stage. Median follow-up was 38 months and there was no correlation with the clinical outcome and ERβ status. Conclusions: In our small sample, it appears that ERβ did not influence the clinical outcome although the number of events is too small to draw conclusions. We have described an association between negative ERβ and mucinous adenocarcinoma CRC which has not been reported previously. [Table: see text]