bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrastaging of sentinel lymph nodes (SLNs) compared to non-SLNs in colorectal (CRca) cancer: Do we need both?
Authors: Wiese D. , Saha S. , Ghanem M. , Yestrepsky B. , Patel M. , Bassily N. , Ng P. , Liu W. , Quiachon E. , Badin J. 
Published: March 2020

4055 Background: SLN mapping (M) accurately stages many solid tumors including CRca. SLNs are 3–5 times more likely to have metastases (mets) when ultrastaged by microsections and IHC as compared to non-SLNs examined by standard pathological methods. It is unknown whether ultrastaging of initially -ve non-SLNs would lead to higher incidence of +ve nodes. Hence, we retrospectively analyzed all initially -ve non-SLNs by microsections and IHC similar to SLNs in CRca patients (pts) undergoing SLNM to determine its impact on final nodal staging. Methods: All CRca pts underwent SLNM by circumferential subserosal injection of 1% lymphazurin. First 1–4 blue nodes were marked as SLNs and ultrastaged by 4 section with H&E and 1 with IHC. All non-SLNs were initially examined by single H& E section and initial staging was made as per AJCC criteria. We re-examined all initially -ve non-SLNs similar to the SLNs by a senior pathologist blinded to prior results. Results: There were 156 pts with Cca and 44 pts with Rca. SLNM was successful in 100% pts with 94% accuracy rate. A total of 2,755 nodes (13.78/pt) were identified, of which 494 were SLNs and 2,261 were non-SLNs. Nodal positivity was 46% and 16% for Cca and Rca pts respectively. Mets were detected in 20.9% of SLNs vs. 8.6% of non-SLNs (p< 0.0001). The exclusive site of nodal mets was detected in 6.5% of SLNs vs.0.8% of non-SLNs (p< 0.0001). Skip mets were found in 6% of pts. After ultrastaging all initially -ve non-SLNs (n=2,065), only 0.58% (12/2065) nonSLNs became +ve in 12 pts. Of these, 10 pts already had +ve SLNs, hence no change of staging occurred. Only 2/200 pts (1%) with initially -ve non-SLNs were found to have a cluster of tumor cells. Thus, ultrastaging of 2065 initially -ve non-SLNs in 200 pts changed the staging from II to III only in 1% of pts. Conclusions: SLNM is highly accurate in staging CRca. The chance of finding additional mets by ultrastaging of all non-SLNs is extremely low (< 1%), hence of little benefit. Therefore, ultrastaging restricted to SLNs alone will assure accurate staging of CRca. [Table: see text] No significant financial relationships to disclose.
Predictors of a true complete response in colorectal liver metastases that disappear radiographically following chemotherapy
Authors: Taylor R. A. , White R. R. , Kemeny N. , Jarnagin W. R. , DeMatteo R. P. , Fong Y. , Blumgart L. H. , D’Angelica M. 
Published: March 2020

4058 Background: During chemotherapy for colorectal liver metastases (LM), some lesions disappear by CT scan. This may represent a true complete response (CR) with eradication of tumor or a reduced sensitivity of imaging due to chemotherapy induced hepatic steatosis. This study aimed to determine the significance of radiologic disappearance of LM treated with chemotherapy and factors predictive of a true CR. Methods: Between 2000 and 2003, 435 patients evaluated by a hepatobiliary surgeon were treated with neoadjuvant chemotherapy for LM. Inclusion criteria were fewer than 12 LM initially, disappearance of one or more LM by CT scan and a clinical follow-up of at least 1 year after disappearance. A pathologic CR (pCR) was defined as the absence of a LM in the resected specimen, a durable clinical CR (cCR) was defined as a LM that did not reappear during follow-up imaging. A LM was defined as found if it was detected by other imaging (MRI), at resection, or if it recurred during follow-up. LM that were found were compared to pCR and durable cCR to determine factors predictive of a true CR. Results: During chemotherapy, 39 (9%) patients had a total of 117 LM disappear by follow-up CT scan. The outcome is shown in the Table . Treatment with hepatic arterial infusion (HAI) chemotherapy (n=22) was associated with a significantly higher rate of pCR or durable cCR (42% vs. 14%, p<0.001). LM were also significantly more likely to represent a pCR or durable cCR when the surrounding liver did not demonstrate steatosis (p<0.001), when the patient’s BMI was <30 kg/m2 (p=0.002), and when a preoperative MRI was performed (p=0.01). Conclusions: Among disappearing LM, a pCR occurs in 37% and a durable cCR in 26%, yielding a true CR rate of 63%. The disappearing LM in patients treated with HAI chemotherapy were more likely to a represent true CR when compared to systemic chemotherapy alone. Hepatic steatosis and obesity impaired the ability to detect lesions by CT scan and MRI improved the preoperative detection rate of disappearing LM. [Table: see text] No significant financial relationships to disclose.
Effectiveness of neoadjuvant chemotherapy including bevacizumab in patients with resectable colorectal cancer liver metastases
Authors: Gruenberger B. , Scheithauer W. , Tamandl D. , Zielinski C. , Schueller J. , Gruenberger T. 
Published: March 2020

4060 Background: Chemotherapy including bevacizumab has become the new standard in the first line treatment of patients with metastatic colorectal cancer (mCRC). Response to chemotherapy has been assessed as major prognostic factor for RFS in resectable mCRC patients, but safety concerns have been raised. We conducted a phase II trial to evaluate the safety of neoadjuvant chemotherapy including bevacizumab (Bev). Methods: Patients with resectable mCRC received six cycles (3 months) of neoadjuvant XELOX (capecitabine 3,500mg/m2/day days 1–7 plus oxaliplatin 85mg/m2 day 1) with bevacizumab (5mg/kg) every 2 weeks. The sixth cycle did not include Bev resulting in a gap of 5 weeks between last Bev and surgery. Primary end points were feasibility of neoadjuvant treatment with this regimen and response rate; secondary end points were feasibility of curative liver resection and perioperative morbidity of the surgical procedure. Results: 54 patients (32 male, 22 female) with a median age of 61 years (SD ± 10.6) were included. The median number of preoperative cycles was 6 (SD ± 2). Grade 3/4 side effects were PNP in 13%, H&F in 3%, diarrhea in 38%, anaemia in 3% and neutropenia in 12% of our patients. Thromboembolic events occurred in 4 patients (7%), hypertension grade III in 2 (4%) and perforation in 1 (2%) patients. A dose reduction of chemotherapy was required in 43%. There were no treatment related deaths. The overall objective response rate for all 54 patients was 74% (40 patients) including 11% pCR. 11 additional patients (20%) had stable disease and only 3 (6%) progressed. Potential curative surgery was performed in all but 5 patients (91%). 2 patients were not resected due to PD, 2 because of pulmonary embolism during chemotherapy and 1 patient because of positive hilar lymph nodes. Conclusions: These data provide evidence that neoadjuvant chemotherapy including bevacizumab can be safely administered in patients with resectable mCRC. A high response rate and a disease control rate of 94% suggest that XELOX + Bev is an effective regimen in this treatment setting. No significant financial relationships to disclose.
Bevacizumab plus XELOX as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer
Authors: Gruenberger T. , Tamandl D. , Puhalla H. , Scheithauer W. , Zielinski C. , Gruenberger B. 
Published: March 2020

4064 Background: Patients (pts) with colorectal cancer (CRC) and liver metastases have a poor prognosis and may benefit from perioperative chemotherapy and disease resection. Bevacizumab (BEV) is proven to improve outcomes in patients with metastatic CRC; however, its impact on surgical complications and hepatic regeneration following liver resection needs to be assessed. Methods: Patients with metastatic CRC with liver metastases potentially curable by resection were eligible for this single-centre, nonrandomised phase II trial. Eligibility criteria define pts at high risk of early recurrence: synchronous liver metastases; primary non-optimally resectable disease or multiple liver metastases. Pts received BEV 5mg/kg q2 weeks plus XELOX (capecitabine 3500mg/m2/day days 1–7 plus oxaliplatin 85mg/m2 day 1 of a 2-week cycle) for 6 cycles. The sixth cycle of therapy did not include BEV, resulting in 5 weeks between the last BEV dose and surgery. Therapy with BEV plus XELOX was restarted 5 weeks after surgery for another 6 cycles. Results: 54 patients have been enrolled and are evaluable having received a median of 6 cycles of BEV plus XELOX: 39 pts underwent liver resection alone, 9 pts also had primary tumor resection (2 are awaiting surgery); major liver resections were performed in 17 pts (35%). 40 pts responded (ORR 74%) and 11 had stable disease. To date, peri- and postoperative events are consistent with previous studies evaluating chemotherapy alone: there was no intra-operative increased bleeding, perioperative blood transfusions were required in only 3 pts (6 %); further surgery was necessary in a single patient. Postoperative liver function and regeneration (assessed by CT 3 months after surgery) were normal in all but one patient (prolonged liver dysfunction due to steatohepatitis). No postoperative mortality occurred and morbidity was encountered in 8 pts (17%). Mean postoperative hospital stay was 8 days (SD ± 3.8). Conclusions: These data suggest that BEV can be safely administered until 5 weeks prior to liver resection in patients with mCRC without increasing the rate of surgical or wound healing complications or severity of bleeding. They are the first to show that neoadjuvant BEV does not affect liver regeneration after resection. No significant financial relationships to disclose.
A phase I study of AEE788, a multitargeted inhibitor of ErbB and VEGF receptor family tyrosine kinases, to determine safety, PK and PD in patients (pts) with advanced colorectal cancer (CRC) and liver metastases
Authors: Xiong H. Q. , Takimoto C. , Rojo F. , Davis D. , Huang J. , Abbruzzese J. L. , Dugan M. , Thomas A. , Mita A. , Steward W. P. 
Published: March 2020

4065 Background: AEE788 (AEE) is an oral inhibitor with potent activity against EGFR, ErbB2, and KDR. This phase I study was to assess the safety, PK, PD, and MTD/DLT of AEE in pts with CRC and liver metastases. Methods: AEE was given PO at 25, 50, 100, 250, 300 or 400 mg/day daily in 28-day cycles (C) to 3–6 pt cohorts. 24-hr PK was obtained on C1, days (D)1, 15 and 28. PK parameters of AEE and active metabolite, AQM674 (AQM) were computed by non-compartmental methods. PD markers were analyzed in skin (SK), and tumor (TU) biopsies pre- and post-treatment. Samples were evaluated by both IHC and Laser Scanning Cytometry (LSC). DCE-MRI was performed at baseline (BL), and on C1D2 and 28 and C2D28. Results: 22 pts were treated at doses of 25 (n=4), 50 (n=3), 100 (n=4), 250 (n=1), 300 (n=4), and 400 mg (n=6). No DLT was reported. The most common AE (> 15%): fatigue (55%), vomiting (46%), diarrhea (41%), nausea (36%), dyspnoea (23%), constipation (18%) pyrexia (18%) and rash (18%). 2 pts had reversible gr 3/4 LFTs. Serum concentration of AEE and AQM increases with dose and dose duration. 7 pts had stable disease at the end of C2. Median time on treatment was 56 days (range 7–168). In SK, at doses =100 mg, pEGFR, pMAPK and Ki67 were inhibited by an average of 51, 54 and 41%, respectively by IHC. In endothelial cell (EC) pKDR/KDR was significantly inhibited (4-fold) in the wound-induced SK in a dose-dependent manner by LSC. In TU, inhibition of pEGFR, pMAPK and Ki67 at 400 mg was 100%, 90% and 39%, respectively by IHC. EC pKDR decreased with dose, however, trend was not significant. 1 out 15 pts who had BL and end of C1 DCE-MRI had > 40% Ktrans reduction. Conclusions: A dose dependent inhibition of pKDR, pEGFR, and pMAPK in skin and tumor was observed. However, no significant effects were observed on Ki67 and apoptosis in TU. No dose dependent reduction in Ktrans from DCE-MRI was observed. These findings were consistent with the lack of clinical activity of AEE up to 400 mg in this patient population. The study has been discontinued without reaching DLT due to safety data from other phase I studies and in favor of different dosing schedules. No significant financial relationships to disclose.
Is chemotherapy failure a contraindication for liver resection in liver metastases of colorectal cancer? A multivariate analysis
Authors: Neumann U. P. , Thelen A. , Jonas S. , Riess H. , Neuhaus P. 
Published: March 2020

4066 Background: Liver resection is the only curative treatment offering a chance of long-term survival in patients with colorectal liver metastases. Chemotherapy is increasingly proposed as neoadjuvant treatment in patients with irresectable liver metastases. However, a large number of patients show progress while on chemotherapy. Recent data indicated that liver resection in patients receiving chemotherapy with tumor progress is associated with poor outcome. The aim of the study was to identify risk factors for poor outcome in patients with preoperative chemotherapy with resectable colorectal liver metastases (CRM). Methods: We retrospectively analyzed the outcome of 168 consecutive patients who underwent liver resection for CRM after systemic chemotherapy between 1995 and 2004. Overall, 132 (78.6%) patients had first line, 24 (14.3%) patients second line and 12 (7.2%) third or fourth line chemotherapy. Three groups of patients were identified according to the chemotherapy response. 48 patients (28.6%) had a tumor response (group 1), in 20 (11.9%) the condition stabilized (group 2), and 100 (59.5%) patients had tumor progression (group 3). Median follow-up was 1.8 yrs (range (6 days - 9.5 yrs). Results: Demographic data, size of largest node, number of nodes, extent of resection and postoperative course were equally distributed between groups. Overall, survival was 89%, 56%, and 31% at 1, 3, and 5 years, respectively. Five-year survival was similar between groups. In the univariate analysis, only incomplete resection and vascular invasion were associated with poor outcome. In the multivariate analysis, only vascular invasion was significantly associated with fatal outcome. Neither the number of lines nor the chemotherapeutic agent was associated with decreased survival. Conclusions: In a large patient population, liver resection offered long-term survival for patients with multiple colorectal metastases, even in cases with tumor growth whilst receiving chemotherapy. This underlines that, whenever a curative resection is possible, surgical resection of liver metastases is justified even in patients with therapy failure due to chemotherapy. No significant financial relationships to disclose.
N9741: Survival update and prognostic factor analysis of oxaliplatin (Ox) and irinotecan (Iri) combinations for metastatic colorectal cancer (MCRC)
Authors: Sanoff H. K. , Sargent D. J. , Campbell M. E. , Morton R. F. , Fuchs C. S. , Ramanathan R. K. , Williamson S. K. , Findlay B. P. , Pitot H. C. , Goldberg R. M. 
Published: March 2020

4067 Background: N9741 randomized 1691 patients (pts) to seven 5FU, Ox and Iri containing regimens for MCRC. After 20.4 months median follow-up, FOLFOX and IROX improved time to progression (TTP) and overall survival (OS) compared to IFL. Here we update OS and TTP, and report an analysis of factors prognostic of pt outcome. Methods: 5 yr OS and TTP were calculated by Kaplan-Meier per treatment (rx) arm. Pt factors [rx arm, age, gender, prior adjuvant rx, body mass index (BMI), performance status (PS), number of disease sites (#sites), neutrophil count (ANC), hemoglobin, platelets, bilirubin, alkaline phosphatase (ALK), aspartate aminotransferase (AST)] were assessed for univariate association with OS, TTP, response rate (RR), and any grade =3 toxicity. Associated factors were included in multivariate Cox and logistic regression models. Results: After a median follow-up of 4.3 yrs, FOLFOX treated pts were more likely to live 5 yrs, 9.2% versus 5.4% for IROX (p=.016) and 3.8% for IFL (p<.001). Median TTP was also significantly longer in the FOLFOX arm, 9.2 mo vs 6.5 mo for IROX (p=<.001) and 6.0 mo for IFL (p=<.001). The prognostic model found higher PS, ANC and ALK, and more disease sites were prognostic of worse OS (see table ). Age = 70 was associated with poorer survival (HR death 1.33, p=.03), but not TTP, RR, or grade =3 toxicity. FOLFOX rx was the most powerful prognostic factor for TTP and OS. The odds of grade =3 toxicity were significantly higher in FOLFOX treated pts (OR 1.65, p<.001) and lower in men (OR .63, p<.001). No significant interactions between rx arm and pt factors were present, suggesting no factor examined is predictive of rx-specific outcome. Conclusions: 9% 5 yr OS in MCRC pts treated with first-line FOLFOX sets a new benchmark. We confirmed pre-rx PS, WBC, and ALK are prognostic for OS, though FOLFOX rx was the strongest prognostic factor. No factor was associated with differential outcome or toxicity by rx arm, thus these factors cannot be used to guide rx selection. [Table: see text] [Table: see text]
Randomized strategical trial of chemotherapy in metastatic colorectal cancer (FFCD 2000–05): Preliminary results
Authors: Bouché O. , Castaing M. , Etienne P. L. , Texereau P. , Auby D. , Bedenne L. , Rougier P. , Gargot D. , Gasmi M. , Ducreux M. 
Published: March 2020

4069 Background: The survival benefit of using a combination therapy instead of keeping it for a second line (L2) has not been demonstrated in metastatic colorectal cancer. The purpose of this trial was to compare the efficacy of simplified LV5FU2 (s) followed by FOLFOX6 (arm A) to FOLFOX6 followed by FOLFIRI (arm B) on progression-free survival after two lines of chemotherapy. We present here preliminary results relating to toxicity, observance and overall survival. Methods: Inclusion criteria: a) non resectable metastases of histologically proven colorectal adenocarcinoma , b) evaluable disease (WHO criteria), c) absence of previous chemotherapy other than adjuvant. Treatment was as follows: LV5FU2s = at day 1, folinic acid 400 mg/m2, 5-FU bolus 400 mg/m2 and continuous infusion over 46 hours 2,400 mg/m2/2 weeks; FOLFOX6 = LV5FU2s + oxaliplatin 100 mg/m2 at day 1; FOLFIRI = LV5FU2s + irinotecan 180 mg/m2 at day 1. Results: 410 pts out of 570 initially planned (early stopping due to slow accrual and new treatments) were included from 02/2002 to 02/2006 (205 in each arm). Median follow-up was 25 months. The median number (range) of cycles (28 days) in first line (L1) was respectively 5 (1–24) and 6 (1–24) in the arms A and B (p=0.01), and for L2 (152 and 144 pts in the arms A/B): 5 (1–17) and 3 (1–33) (NS). In the arms A and B, 74% and 70% of pts had L2. L1 was stopped for toxicity for 1% and 16% of the pts in arms A and B (p<0.0001); L2 respectively for 15% and 2% pts (p<0.0001). The percentages of pts presenting at least a grade 3–4 hematologic toxicity (mainly neutropenia) by arm were: 6% versus 37% (p<0.0001) for L1 and 30% versus 27% (NS) for L2; grade 3–4 non hematological toxicity (grade 2–4 neurotoxicity): 26% (1%) versus 56% (64%)(p<0.0001; p<0.0001) for L1 and 54% (60%) versus 46% (40%) of the pts for L2 (NS; p<0.01). No toxic death was observed in the arm A against 5 in the arm B: 3 in L1 and 2 in L2. Overall survival medians were 17 and 16 months in arms A/B (logrank p=0.64) (preliminary results, 291 observed deaths). Conclusions: This trial does not show any substantial difference in treatment duration and overall survival between both arms and shows a more important toxicity in the arm with first line combined chemotherapy. No significant financial relationships to disclose.
Cetuximab (C), oxaliplatin (Ox) and fluoropyrimidine (Fp): Toxicity during the first 12 weeks of treatment for the first 804 patients entered into the MRC COIN (CR10) trial
Authors: Maughan T. 
Published: March 2020

4070 Background: COIN is a 3-arm trial comparing continuous chemotherapy (CT) plus C or intermittent CT with standard continuous CT (OxFp) in the first-line treatment of advanced colorectal cancer (ACRC). Methods: Eligible patients have measurable, inoperable ACRC; no prior CT for metastases; PS 0–2; GFR >50; ALP <5 xULN; bili <1.25 xULN. Patients and/or clinicians choose the OxFp regimen, either FOLFOX (Braun,M BJC 89:1155f, 2003) or capecitabine (Cap) with Ox. Thereafter, randomization is 1:1:1 between: (A) OxFp; (B) OxFp plus weekly C; or (C) Intermittent OxFp. In Arms A and B treatment is given until progression, cumulative toxicity or patient choice, in Arm C it is stopped at 12 wks in stable/responding patients and reintroduced following progression off treatment. Primary endpoint is Overall Survival (OS). The trial aims to recruit 2,421 patients over 3.5 years. Release of this preliminary toxicity data has been approved by the independent Data Monitoring Committee (DMC). Results: 804 patients were randomised between 03/05 and 07/06 and 12 week toxicity is available on approx. 85% of patients. 62% of patients received Ox + cap and 38% received FOLFOX. Grade 3 /4 toxicities (%) in the first 12 weeks by regimen are reported below. Conclusions: The addition of cetuximab to OxFp combinations results in increased grade 3/4 toxicities overall and specifically in GI, skin rash and lethargy. Cap combination is associated with more GI toxicity but less neutropenia. Unexpectedly, no hypersensitivity reactions have yet been seen on FOLFOX (with or without C). [Table: see text] [Table: see text]
Irinotecan/5-FU/FA (I-FU) or 5-FU/FA (FU) first-line therapy in older and younger patients with metastatic colorectal cancer: Combined analysis of 2,691 patients in randomized controlled trials
Authors: Folprecht G. , Seymour M. T. , Saltz L. , Douillard J. Y. , Stephens R. J. , Van Cutsem E. , Rougier P. , Maughan T. S. , Köhne C. H. 
Published: March 2020

4071 Background: Irinotecan containing first line therapy has been shown to improve efficacy in first line therapy. Pooled analyses demonstrated that elderly patients benefit in a similar way as younger patients if 5-FU or 5-FU/oxaliplatin is administered as palliative or adjuvant treatment within clinical trials (Sargent, NEJM 2001, Folprecht, Ann Oncol 2004, Goldberg JCO 2006). Methods: We present an updated metaanalysis using source data of randomized trials (Saltz 2000, Douillard 2000, Köhne 2005 [EORTC 40986] and Seymour 2005 [FOCUS]) and compared the efficacy and toxicity in older (=70 years) and younger (<70 years) patients receiving first line 5- FU/FA with or without irinotecan. Randomized patients who did not receive treatment were excluded. Results: A total of 2,691 pts. was enrolled into the analysis ( table 1 ). There was no imbalance regarding risk factors (ECOG PS, WBC, No. of tumor sites, alkal. phosphatase, LDH) between elderly and younger patients. Older and younger patients had significantly improved response rates and PFS with I-FU compared to FU. Younger patients had significantly longer OS with I-FU, older patients a trend to longer OS with I-FU ( table 1 ). I- FU was associated with more grade >= 3 toxicity in the general population, but there were no significant differences regarding toxicity between older and younger patients ( table 1 ). Conclusion: Patients over 70 yrs who are selected for inclusion in phase III trials derive similar benefits from irinotecan-containing chemotherapy, and with similar risks of toxicity, compared with younger patients. [Table: see text] [Table: see text]