bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of genetic variants to predict clinical outcome in patients (pts) with metastatic colorectal cancer (mCRC) treated with first-line 5-FU or capecitabine in combination with oxaliplatin and bevacizumab (FOLFOX/BV or XELOX/BV)
Authors: Singh H. , Pohl A. , El-Khoueiry A. , Lurje G. , Zhang W. , Yang D. , Ning Y. , Shriki J. , Iqbal S. , Lenz H. 
Published: August 2020

4070 Background: Recent studies suggested polymorphisms involved in angiogenesis related genes associated with clinical outcome in pts treated with the VEGF-inhibitor bevacizumab. (Schneider et al. JCO 2008, Manegold et al ASCO 2008). We evaluated functional polymorphisms involved in angiogenesis- (VEGF, KDR, IL-6, CXCR1 and-2), apoptosis (p53) and cell-proliferation (MMP2,-7 and-9, ICAM)-related pathways in an expanded patient cohort for their potential prognostic or predictive role in clinical outcome. Methods: Genomic DNA was extracted from 79 mCRC pts (treated with first-line FOLFOX/BV or XELOX/BV at USC) from peripheral blood. Genotyping was performed using PCR-RFLP assays or direct sequencing. Results: 79 pts (47 men, 32 women) with a median age of 56 years (range 29–81), were treated with either FOLFOX/BV (33 pts) or XELOX/BV (46 pts). Radiologic response: 2/79 pts (3%) CR, 41/79 pts (52%) PR, 32/79 pts (41%) SD and 3/79 pts (4%) DP. At a median follow-up of 32.0 months (range: 1.4- 47.8 months), the median time to progression was 10.8 months (95% CI: 8.1–14.9). We found IL-6 G- 174C (p=0.025, Fisher's exact test) and p53 codon 72 (p=0.029, Fisher's exact test) polymorphisms associated with response to BV-therapy. Furthermore, there were statistically significant associations between genomic polymorphisms in MMP-9, CXCR-1 and PFS (p=0.023 and p=0.014, respectively, log-rank test). Pts with 2 G- alleles in CXCR-1 G+2607C (median PFS=13.7 months, 95% CI:8.4–16.4) and pts homozygous for the C-allele in MMP-9 C-1562T (median PFS= 13.9 months, 95% CI: 10.1–15.8) had longer PFS compared to pts with any C-allele in CXCR-1 G+2607C (median PFS = 7.9 months, 95% CI: 6.9–10.2) and pts with any T-allele in MMP-9 C-1562T (median PFS 7.2 months, 95% CI: 5.3–11.0), respectively. Conclusions: These are the first data to predict clinical outcome in mCRC pts treated with FOLFOX/BV or XELOX/BV. Our data demonstrate that functional polymorphisms in angiogenesis related genes predict response and PFS in pts treated with the angiogenesis- inhibitor BV. However, confirmation of these findings in larger, prospective genotype-guided clinical trials is warranted. [Table: see text]
Updated analysis of a phase II study (20060314) of panitumumab (pmab) with FOLFIRI as first-line treatment of patients (pts) with metastatic colorectal cancer (mCRC)
Authors: Greil R. , Letocha H. , Gamelin E. , Thaler J. , Hofheinz R. , Mineur L. , Fernebro E. , Karthaus M. , Wright L. , Köhne C. ,   20060314 Study Group
Published: August 2020

4085 Background: The fully human anti-epidermal growth factor receptor monoclonal antibody pmab, has proven monotherapy activity in chemotherapy refractory mCRC pts with wild-type KRAS-expressing tumors. This first-line, single-arm phase II study is prospectively evaluating whether KRAS status predicts response to treatment when pmab is combined with FOLFIRI. Methods: In this ongoing study, pts with histologically confirmed mCRC (no prior systemic treatment) and ECOG PS 0–2 were enrolled at 36 sites across Europe. Pmab (6mg/kg) and FOLFIRI are administered every 2 weeks. The primary endpoint is objective response rate; secondary endpoints include disease control rate, duration of response, time to response, progression-free survival, time to progression and safety. Results: Data cut-off for the initial interim analysis was 27 June 08 and pending approval of protocol amendment 2, the cut off date for 16 week response rate is 15 Oct 08. Of the 154 pts enrolled, 68% are male; median age is 64 yrs (range, 21–84) and the majority (95%) of pts had ECOG PS 0–1. All pts have received at least one cycle of study treatment; 18% of pts have received ≤2 cycles of full combination therapy and the median number of cycles received is 6. At time of data cut-off, 112 patients (73%) were still receiving at least one element of combination therapy and 29% had stopped treatment with pmab. The most common reason for discontinuing treatment was disease progression (10%). Median follow-up time was 14.3 weeks for all enrolled pts. A total of 97% of patients had experienced at least one adverse event (any grade) and 55% of patients had experienced a grade 3/4 adverse event. There were four reported grade 5 events (hematemesis, rectal hemorrhage, vena cava thrombosis, general physical health deterioration). At time of interim analysis, tissue samples for KRAS analysis are available for approximately 80% of patients. Conclusions: Combining pmab with FOLFIRI in the first-line setting appears to be a well-tolerated regimen. Response rate at 16 weeks in the overall population and by KRAS status and updated safety will be presented. [Table: see text]
Liver regenerative nodular hyperplasia consecutive to preoperative chemotherapy: Impact on outcome of liver surgery for colorectal metastases
Authors: Wicherts D. A. , de Haas R. J. , Sebagh M. , Ciacio O. , Lévi F. , Paule B. , Azoulay D. , Bismuth H. , Castaing D. , Adam R. 
Published: August 2020

4097 Background: Regenerative nodular hyperplasia (RNH) represents the worst evolutive stage of vascular lesions induced by prolonged chemotherapy on the liver. Its incidence and impact on the outcome of resection for colorectal liver metastases (CLM) are however unknown. We evaluated the effect of RNH on postoperative morbidity and assessed its evolution in time at repeat hepatectomy. Methods: All patients that underwent hepatectomy for CLM between January 1990 and November 2006 after 1 line of chemotherapy of more than 6 cycles were included. Detailed histopathologic analysis of the nontumoral liver was performed at first and repeat hepatectomies according to a standard format. Results: Of 146 included patients, 24 (16%) received 5- fluorouracil (5-FU) and leucovorin (LV) alone, 92 (63%) had 5-FU, LV and oxaliplatin, 18 (12%) had 5-FU, LV and irinotecan, and 12 (8%) were treated by 5-FU, LV, oxaliplatin and irinotecan. Overall, RNH occurred in 22 of 146 patients (15%). Patients treated by oxaliplatin more often had RNH compared to oxaliplatin-naïve patients (22% vs 4%) (P=0.003). The presence of RNH was associated with increased postoperative hepatic morbidity (23% vs 11%) (P=0.05). None of the RNH patients died within 60 days postoperatively. A preoperative gamma-glutamyltransferase level >80 U/L and a total bilirubin level >15 μmol/L were independent predictive factors of RNH at first hepatectomy. Two of 22 patients with RNH underwent repeat hepatectomy. RNH disappeared at second hepatectomy in both patients following prolonged treatment with irinotecan. Conclusions: Patients with CLM that receive prolonged courses of preoperative oxaliplatin have an increased risk of RNH and associated postoperative hepatic morbidity. Upfront treatment with short courses of highly effective regimens may therefore be most appropriate. In addition, the continuation of oxaliplatin should be discouraged in case of RNH to avoid its negative effects on further surgery. No significant financial relationships to disclose.
The need for a revised staging system of metastatic (M) colorectal cancer (CRC): Evidence from a national perspective on survival following surgically treated (HPX) liver metastases
Authors: Morris E. , Thomas J. , Forman D. , Quirke P. , Cottier B. , Poston G. J. 
Published: August 2020

4099 Background: AJCC V.6 (2002) places all patients with MCRC beyond the lymph node basin of the primary tumor in a homogenous Stage 4. Patients with inoperable hepatic MCRC can be made operable with curative intent with chemotherapy yet remaining in Stage 4. Via the linkage of routine health datasets across England this population-based study sought to determine the impact of HPX for MCRC on stage-matched survival at initial presentation. Methods: All patients between 1998–2001 undergoing surgery for CRC in England were identified via the national-linked cancer registry HES dataset. All care episodes in the 3 years following initial colorectal surgery were examined to determine the frequency of subsequent HPX. Kaplan-Meier curves and log- rank tests were used to examine 5-year survival following HPX for MCRC compared to all Stage 3 and Stage 4 at presentation. Survival was calculated from the date of resection of each patient's primary colorectal tumor. Results: 68,307 individuals were identified as undergoing surgery for primary CRC over the study period. 20,298 were Stage 3 at presentation. 1,483 (2.2%) subsequently underwent HPX <3 years of their colorectal operation. 55 patients died within 30 days of HPX (mortality rate: 3.7%). Crude 5-year survival of patients who underwent HPX was 41.6% (95%CI 39.0–44.1%) from time of initial colectomy. This survival rate was significantly better than that for both Stage 3 (38.6% (95%CI 37.9%-39.2%, P<0.01) and 4 (6.1% 95%CI 5.3–6.9%, P<0.01) overall. Conclusions: 5-year survival following HPX for MCRC is better than that seen overall for all Stage 3 patients (with MCRC confined to the regional draining lymph node basin) following initial colectomy. Our data support the hypothesis that all MCRC that is potentially resectable with curative intent should be stratified within Stage 3, and Stage 4 should only contain those MCRC patients for whom surgery is not an option. If further evidence emerges to support this theory then a revision of the current staging system will be required. [Table: see text]
Does microsatellite instability predict the effect of adjuvant chemotherapy in stage III colorectal cancer? A meta-analysis
Authors: Des Guetz G. , Uzzan B. , Nicolas P. , Chouahnia K. , Perret G. , Zelek L. , Morere J. 
Published: August 2020

4121 Background: Microsatellite instability (MSI) is a prognostic factor in colorectal cancer. Whether it predicts the effect of adjuvant chemotherapy (CT) on overall survival (OS) and relapse-free survival (RFS) is controversial. Methods: Studies were identified by an electronic search using online PubMed, with simultaneous keywords (colorectal neoplasm, microsatellite instability, chemotherapy, prognosis). Abstracts from ASCO and AACR proceedings were reviewed. Articles were obtained from cross-checking of references and from a previous prognostic meta-analysis (MA) (Popat, 2005). We used EasyMA software, available online. A Hazard Ratio (HR) < 1 for MSI-high (MSI-H) status compared with microsatellite stable (MSS) meant a better survival. Results: Our MA found 21 studies (4 abstracts). Statistical calculations were performed in 11 studies (5087 patients including 2879 receiving 5FU-based CT; mean age: 63 years; 1489 stage II, 2648 stage III (64%)). MSI-H was found in 644 patients (15% of total), MSS in 3624. Seven studies (2 randomized) assessed 2 cohorts receiving or not adjuvant CT, 4 studies only included patients receiving CT. Global HR OS (9 studies) was 0.79 (95% confidence interval or CI: 0.64–0.98; p = 0.03). Global HR RFS (8 studies) was 0.67 (95% CI: 0.54–0.83; p < 0.001). A MA on stage III patients (4 studies, 719 patients, 137 MSI-H) found a higher survival among MSI-H than MSS patients receiving CT (HR OS: 0.71, 95% CI 0.49–1.03; HR RFS 0.56, 95% CI 0.42–0.75). Interaction between MSI status and CT status was statistically significant on OS and RFS (4 studies). A MA among MSI-H patients (7 studies) found no survival difference between patients under CT or not: HR OS: 0.70 (95% CI 0.44–1.09), HR RFS: 0.96 (95% CI: 0.62–1.49). Conclusions: Adjuvant CT significantly improved survival in MSI-H compared with MSS patients. MSI-H stage III patients receiving CT survived more than MSS. MSI-H status did not predict response to CT compared with no treatment. No significant financial relationships to disclose.
Placebo-controlled, double-blind, prospective, randomized study of the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: A report from the PROMID study group
Authors: Arnold R. , Müller H. , Schade-Brittinger C. , Rinke A. , Klose K. , Barth P. , Wied M. , Mayer C. , Aminossadati B. ,   PROMID Study Group
Published: August 2020

4508 Background: Octreotide is currently used for the control of symptoms in patients with gastroenteropancreatic neuroendocrine tumors (NETs). However, the ability of long-acting somatostatin analogues to control the growth of well-differentiated metastatic NETs is a matter of debate. The analysis of the first randomized, double-blind, placebo-controlled, multicenter, phase IIIb study of octreotide LAR in patients with metastatic NETs of the midgut is presented. Methods: Treatment-naïve patients with histologically confirmed locally inoperable or metastasized well-differentiated NETs and a Karnofsky index >60 were randomized to receive either octreotide LAR 30 mg/month (mo) or placebo for 18 mos, or until tumor progression or death. The primary endpoint was median time to tumor progression. Secondary endpoints included objective tumor response rate (WHO criteria), measured every 3 mos, as well as symptom control and overall survival. This was a planned interim analysis using the Lan-DeMets error spending approach. Results: Eighty-five patients (n=43 octreotide LAR; n=42 placebo) have been enrolled to date and data from 67 patients with tumor progressions and 16 deaths (n=7 octreotide LAR; n=9 placebo) are included here. Median time to tumor progression in the octreotide LAR and placebo groups were 14.3 mos and 6 mos, respectively (HR: 0.34; 95% CI: 0.20–0.59; P=0.000072). After 6 mos of treatment, stable disease was seen in 67% and 37.2% of patients treated with octreotide LAR and placebo, respectively. Due to the low number of observed deaths, median survival time could not be estimated. Conclusions: Octreotide LAR significantly lengthens median time to tumor progression compared with placebo in patients with metastatic NETs of the midgut. Patients treated with octreotide LAR had a 66% risk reduction of tumor progression compared with patients receiving placebo. Octreotide LAR demonstrates substantial tumor control and shows a more favorable antiproliferative response than placebo as two-thirds of patients treated with octreotide LAR achieved stable disease at 6 mos. [Table: see text]
A randomized phase II trial of irinotecan plus oxaliplatin versus oxaliplatin, fluorouracil (5 FU), leukovorin (LV) as first-line treatment in advanced gastric cancer
Authors: Boukovinas I. , Androulakis N. , Polyzos A. , Vardakis N. , Amarantidis K. , Bozionelou V. , Kouroussis C. , Giassas S. , Christophyllakis C. , Mavroudis D. 
Published: August 2020

4536 Background: To compare the efficacy and tolerance of two oxaliplatin-based regimens as first-line treatment of advanced gastric cancer. Methods: Chemotherapy-naïve patients with measurable recurrent or metastatic gastric adenocarcinoma, PS (ECOG) 0–2 and adequate organ functions were randomly assigned to receive either irinotecan 200mg/m2 and oxaliplatin 80mg/m2 (IO), every 21 days or oxaliplatin 85mg/m2 on day 1, 5-FU 400 mg/m2 (over 1 hour infusion) + 600mg/m2 (over 22 hours infusion) on days 1 and 2, leucovorin (LV) 200mg/m2 on days 1 and 2 (FOLFOX4) every 2 weeks. Study endpoints: Overall Response Rate (ORR), Toxicity Time to Progression (TTP) and Survival (S). Results: 138 patients were enrolled and all were evaluable for response. Median number of cycles administered was 5.5 (range 1–10) for IO and 7 (range 1–18) for FOLFOX4. In an intent-to treat analysis the ORR (RR+CR) was 29.4% for IO arm and 34.3 % for FOLFOX4 arm (p= 0.587). The median response duration was 5.63 months (mo) for IO arm and 6,6mo for FOLFOX4 arm. Median TTP was 4.2mo and 6,1mo for IO and FOLFOX4 arm respectively (p= 0.012). Median OS was 9.4mo for IO and 11.97mo for FOLFOX4 (p= 0.456). Toxicity was acceptable, with one toxic death in each arm. Grade 3–4 vomiting (7.3%), diarrhea (11.8%), neutropenia (22%) and febrile neutropenia (5.9%) occurred more frequently in IO arm, while anaemia (4.3%) and grade II neurotoxicity (11.4%) was more frequent in FOLFOX4 arm. Conclusions: Both regimens are well tolerated and active in advanced gastric cancer. Based on the TTP and toxicity profile, the FOLFOX4 regimen merits to be further evaluated in prospective phase III trials. No significant financial relationships to disclose.
Updated result on the 2.5-year follow-up of GC0301/TOP-002: Randomized phase III study of irinotecan plus S-1 (IRI-S) versus S-1 alone as first-line treatment for advanced gastric cancer (AGC)
Authors: Tsuburaya A. , Narahara H. , Imamura H. , Hatake K. , Imamoto H. , Esaki T. , Kato M. , Furukawa H. , Hamada C. , Sakata Y. ,   GC0301/TOP-002 Study Group
Published: August 2020

4544 Background: IRI-S had longer in median survival time (MST) than S-1 alone, and was well tolerated in previously untreated AGC, but not statistically significant. Considering 68 patients (pts) were censored, further follow-up was needed to confirm the OS with more precision (Imamura et al. ASCO-GI 2008). We now present updated results of OS and exploratory analysis with the prolonged 2.5 year follow-up data. Methods: Treatments Arm A (oral S-1 80 mg/m2/day from Day 1 to 28, q6w), or Arm B (IRI-S; oral S-1 80 mg/m2/day from Day 1 to 21 and intravenous irinotecan 80 mg/m2 on Days 1 and 15, q5w) were continued until disease progression or unacceptable toxicities were observed. The primary endpoint was to compare OS between groups. This updated result was regarded as exploratory position. Results: Although the MST of Arm A was 319 days (95%Cl: 286–395) and of Arm B was 389 days (95%Cl: 324–459), Arm B didn’t show statistically significant superiority to Arm A (log-rank test p=0.54; hazard ratio (HR) =0.93). The 1-year survival was 45.0% in Arm A and 52.0% in Arm B, and the 2-year survival was 22.5% and 18.0%, respectively. Response rate was significantly different (Arm A/B, 26.9%/41.5%; chi-square test p=0.04) in 187 patient evaluated by RECIST criteria. Time to treatment failure was also favored in Arm B (median=138 days) compared to Arm A (111 days; log-rank test p=0.16; HR=0.85). In subset analyses, two groups showed possibility of clinical benefit in Arm B. The HR of diffuse type group was 0.71 (95%Cl: 0.52–0.96), and of PS1, 2 group was 0.63 (95%Cl: 0.42–0.95). As post protocol treatment, 45.6% of Arm A patients received an irinotecan-based regimen, and the MST of them was 496 days (95%Cl: 395–573). Conclusions: IRI-S did not show statistically significant superiority to S-1 alone in OS with this follow-up data. Post protocol treatment, effective treatment after S-1 failure might have affected survival. According to exploratory analyses, IRI-S may have clinical benefit in early-term of treatment, group of the diffuse type and that of PS1, 2. We need more considering predictive factors, because the gastric cancer is heterogeneous adenocarcinoma. [Table: see text]
The association of PET response with complete pathological response (CPR) and residual nodal disease (RND) after induction chemoradiotherapy (CRT) and resection of esophageal cancer: A review of 493 cases
Authors: Barnett S. A. , Rizk N. P. , Adusumilli P. S. , Park B. J. , Bains M. S. , Flores R. M. , Goodman K. A. , Ilson D. H. , Akhurst T. J. , Rusch V. W. 
Published: August 2020

4552 Background: RND and lack of CPR of the primary tumor correlate with poor survival after induction CRT and resection of esophageal cancer. PET response to CRT (SUVmax change and post-induction SUVmax) is used by some clinicians as an indicator of CPR and RND in order to stratify patients after CRT to observation alone vs completion resection. We aimed to investigate the association of PET response with CPR and RND after induction CRT and resection of esophageal cancer. Methods: An IRB-approved retrospective review of an institutional surgical database identified patients who underwent resection of esophageal squamous cell (SCC) and adeno carcinoma (AC) following CRT. The database was locked on Sept 30, 2008. Categorical variables were analyzed by chi square, continuous variables by t-test, and survival by the Kaplan-Meier method. Results: From 1/96 to 3/08, 493 patients were identified, 82% were male. Median age was 62, chemotherapy cisplatin-based in 87%, mean radiation 50 Gy, in-hospital mortality 4.1% and R0 resection rate 88%. Pathology revealed AC in 80%, lack of CPR in 73% and RND in 35%. While in AC patients CPR and lack of RND were both associated with prolonged survival, PET response was not associated with either. In SCC patients, prolonged survival was associated with CPR but not with lack of RND. In SCC, PET response was associated with CPR but not RND. In these patients, reduction in SUVmax <50, 50–75 and >75% was associated with CPR rates of 29, 44 and 85% respectively (p=0.02). Conclusions: These results do not support the use of PET response to justify observation alone after CRT in esophageal AC. With respect to SCC, though exploratory, these provocative results support further study of the use of PET response to predict CPR. [Table: see text] No significant financial relationships to disclose.
A phase II study of bevacizumab, docetaxel, and oxaliplatin in gastric and GEJ cancer
Authors: El-Rayes B. F. , Patel B. , Zalupski M. , Hammad N. , Shields A. , Heilbrun L. , Venkatramanamoorthy R. , Philip P. 
Published: August 2020

4563 Background: VEGF (vascular endothelial growth factor) has a central role in angiogenesis, tumor growth and metastasis of gastric cancer. Bevacizumab, an anti-VEGF monoclonal antibody, has demonstrated anti-tumor activity in multiple diseases. This phase II study was undertaken to determine the effects of adding bevacizumab to a regimen of docetaxel and oxaliplatin. Methods: The primary endpoint was time to progression (TTP) in patients with locally advanced or metastatic adenocarcinoma of the gastric or gastroesophageal junction treated with docetaxel, oxaliplatin and bevacizumab. Previously untreated patients with a performance status (PS) of 0–1 were eligible for this study. Patients received bevacizumab 7.5 mg/kg, docetaxel 70 mg/m2 and oxaliplatin 75 mg/m2 administered on day 1 of a 21 day cycle. Results: A total of 23 patients (median age 57, males 70%, gastric 52%) were enrolled on the study. Median PS was 1. The median number of cycles was 5. Ten patients are still receiving treatment on study. Partial responses were documented in 10 (59%) patients and stable disease in 7 (41%). No treatment related deaths were observed. The most commonly reported grade 3–4 toxicities were neutropenia (13%), leukopenia (4%), fever (4%), acute neuropathy (4%), and hypertension (4%). Gastrointestinal (GI) perforation occurred in 3 patients. Perforation was not found at the tumor site in the patient who required surgery. The site of perforation could not be ascertained in the second patient who was managed medically. Both patients had had no prior surgical resection of the primary tumor. The third perforation presented as a tracho-bronchial fistula. The patient had previously undergone surgical resection of his primary tumor after receiving chemoradiotherapy to the thoracic area. Conclusions: The regimen of docetaxel, oxaliplatin and bevacizumab appears to be very active. The development of GI perforations in 3 patients is of concern. At this time, bevacizumab should not be used in gastric or gastroesophageal junction cancers outside of a clinical trial until its safety is well established. [Table: see text]