bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of lymph node ratio improves staging and selection criteria for adjuvant therapy of gastric cancer
Authors: Coburn N. G. , Swallow C. J. , Kiss A. , Law C. 
Published: March 2020

4051 Background: Despite 1997 American Joint Commission on Cancer (AJCC) guidelines stipulating assessment of ≥15 lymph nodes (LN) for staging of gastric cancer, only one third of patients in the Surveillance, Epidemiology and End Results (SEER) database from 1998–2002 had ≥15 LN assessed (ASCO 2005 #4004), with resultant understaging and probable under-treatment. In series from Asia and Europe, Lymph Node Ratio (LNR), the ratio of positive to total LN assessed, has been shown to be more accurate for staging than number of positive LN. However, most of these excluded cases with <15 LN assessed. We examined the utility of LNR in a North American population. Methods: Using SEER data, we identified 9503 M0 resected gastric cancer cases from 1988–2002. LNR was categorized as 0%, 1–10%, 11–30%, 31–50% and >50%. For node negative cases (LNR = 0%, n = 3652), we stratified by number of LN assessed (A=1–4; B = 5–9; C = 10–14; D≥15). For each AJCC stage or LNR strata, the degree of understaging in patients with inadequate LN assessment was measured by survival difference on Kaplan-Meier curves. Cox proportional hazard ratio (HR) models determined the effect of stratifying node negative patients and the accuracy of LNR for prognostication. Results: 27% of patients had a LNR > 50%, a high proportion compared to Asian series. Fewer nodes assessed resulted in a higher likelihood of being node negative. In node negative cases, the HR of death increased for those with fewer LN assessed (vs. Group D, with 95% CI): A: HR=1.6 (1.5–1.8); B: HR = 1.3 (1.1–1.5); C: HR = 1.3 (1.1–1.5). Understaging was observed for patients with inadequate LN assessment when AJCC criteria were used (p < 0.0001); this effect significantly decreased by using LNR. LNR had superior prognostic accuracy in Cox models. Conclusions: This study examines LNR in the largest series of resected gastric cancer in the literature, and the only one in which the majority of cases were inadequately staged. LNR significantly decreases understaging and improves prognostic ability. Node negative patients, nearly one third of cases, should be risk stratified by number of LN assessed, and considered for adjuvant therapy on this basis. LNR should be used to stratify node positive patients in clinical trials, and to provide more accurate staging and prognostication. No significant financial relationships to disclose.
Possible individualized therapy by early assessment of response during neoadjuvant radiochemotherapy in esophageal squamous cell carcinoma patients by 18-FDG-PET
Authors: Brücher B. L. , Wieder H. , Busch R. , Becker K. , Lordick F. , Molls M. , Siewert J. , Schwaiger M. 
Published: March 2020

4060 Background: Response evaluation by positron emission tomography with the glucose analog [18F]-fluorodeoxyglucose (FDG-PET) has been used in patients with esophageal squamous cell carcinoma (ESCC) after neoadjuvant radiochemotherapy (RTx/CTx). This prospective study was undertaken to compare FDG-PET assessment of tumor response during RTx/CTx with histopathology in patients with ESCC, and to correlate the findings with survival. Methods: Patients (n=61) with histologically proven intrathoracic ESCC (cT3, cN0/+, cM0) underwent preoperative, simultaneous RTx/CTx followed by esophagectomy between 1996 and 2005. The patients underwent FDG-PET prior to and 2 weeks after the begin of RTx/CTx (20Gray). Histopathological response was quantified as the percentage of residual tumor cells. The threshold pre-therapy-to-during-therapy decrease in standardized uptake value by FDG-PET used to define metabolic responders (ΔSUVR) was -30%. Results: Receiving-operator-curve analysis (ROC) for determination of metabolic response revealed an area-under-curve (AUC) of 7140 (p=0.005) with a sensitivity of 76%, specificity (70%), a positive predictive value of 81% and a negative predictive value of 64% (p<0.0001). Responder by FDG-PET during the neoadjuvant treatment (p=0.016) as well as Histopathology (p<0.0001) showed substantially better survival compared to nonresponders. Conclusions: Changes in tumor metabolic activity by FDG-PET during neoadjuvant RTx/CTx allows an accurate determination of response due to the multimodal approach in patients with ESCC. This stratification may lead to a change of the neoadjuvant into a definitive therapy concept in nonresponders (individualized tumor therapy). [Table: see text]
The predictive value of baseline fluoro-deoxy-glucose positron emission tomography (FDG-PET) standardized uptake value (SUV) for overall survival in patients (pts) with locally advanced esophageal and gastroesophageal junction (GEJ) cancer
Authors: Abou-Jawde R. M. , Rybicki L. , Bybel B. , Rice T. , Carroll M. , Mekhail T. , Videtic G. , Adelstein D. J. 
Published: March 2020

4062 Background: The predictive value of FDG-PET SUV in pts with esophageal and GEJ cancer has been subject of recent interest. The heterogeneity of disease stages and treatments made interpretation of reported data difficult.We evaluated the value of baseline FDG-PET SUV in a homogeneous patient (pt) population treated in a uniform fashion. Methods: Retrospective analysis of 71 pts with stages II-IVa esophageal and GEJ cancer treated on 2 phase 2 trials at the Cleveland Clinic Foundation. Data was collected on baseline pt and tumor characteristics, baseline SUV uptake, and outcomes. Results: All pts were treated with preoperative concurrent fluorouracil/cisplatin chemoradiotherapy (CRT); 69 pts proceeded to esophagectomy and 58 pts received additional postoperative adjuvant CRT. Median pt age was 60 (range 33–75) years, 86% were male, 89% had adenocarcinoma, 35%, 41% and 24% had stage II, III and IVa disease respectively. Pts have been followed for a median of 14 (range 3–50) months. All pts underwent a baseline FDG-PET scan with a mean primary site SUV of 8.9 (range 0–28.2). Pathological response (complete or partial) was achieved after induction CRT in 54% and was more likely in those with a baseline primary site SUV ≥ 7.3 (OR: 3.95, 1.43–10.9, P=0.008). Recurrence developed in 33 pts (46.5%) with distant metastases identified in 31 of these 33. The Kaplan-Meier 2-year projected overall survival for all 71 pts is 58% with a median of 31 months. Mortality was less in pts with baseline SUV ≥ 5.0 (HR: 0.44, 0.20–0.94, P = 0.033). After adjusting for clinical stage at diagnosis, tumor location and histology, baseline SUV ≥ 5 was still predictive of improved survival in multivariate analysis (HR: 0.35, 0.15–0.85, P = 0.02). Conclusions: In this retrospective analysis, esophageal and GEJ cancer pts with a higher baseline primary site SUV were more likely to respond to induction CRT and had better overall survival. This observation suggests that the subset of pts with more metabolically active tumor may derive greater benefit from multimodality treatments that include CRT. A prospectively designed trial would be required to confirm this hypothesis. No significant financial relationships to disclose.
Phase II cisplatin, irinotecan, cetuximab and concurrent radiation therapy followed by surgery for locally advanced esophageal cancer
Authors: Enzinger P. C. , Yock T. , Suh W. , Fidias P. , Mamon H. , Choi N. , Lehman N. , Lawrence C. , Lynch T. , Fuchs C. 
Published: March 2020

4064 Background: Weekly irinotecan, cisplatin, and concurrent radiation therapy is a well-tolerated, active regimen in locally advanced esophageal cancer. (Ilson. JCO 2003) Cetuximab, an EGFR inhibitor, is a potent radiation sensitizer in head and neck cancer. (Bonner. Proc ASCO 2004) Methods: In this phase II trial, patients (pts) with T2–4N0–1M0–1A esophageal adenocarcinoma (A) or squamous cell carcinoma (S) receive 5040 cGy/28 fractions of radiation therapy (RT) and concurrent weekly cisplatin 30mg/m2 plus irinotecan 65 mg/m2 on weeks 1, 2, 4, and 5, followed by surgery 4–8 weeks after completion of RT. Additionally, pts receive weekly infusions of cetuximab 250 mg during RT, up to one week before surgery, and for 6 months following surgery. Results: Seventeen pts have been entered: male: female = 14:3, median age 54, ECOG PS 0:1 = 6:11, A:S = 17:0, stage IIA:IIB:III:IVA = 6:1:8:2, tumor location-esophagus-mid:lower:gastroesophageal junction = 1:4:12, >10% weight loss-yes:no = 8:9. Of 17 pts entered, 15 pts have proceeded to surgery, 1 pt died from Aspergillus infection resulting in respiratory failure and sepsis, and 1 pt is pending surgery. Of the 15 pts who underwent surgery, 2 (13%) had a complete pathologic response; pathologic stage for other pts: 0 = 1, I = 3, IIA = 3, IIB = 1, III = 4, IV = 1. Grade III/IV toxicity (17 pts) was: diarrhea 9 pts, neutropenia 9 pts, febrile neutropenia 5 pts, anorexia 5 pts, vomiting 4 pts, fatigue 3 pts, mucositis 1 pt. Chemotherapy dose attenuation was required for diarrhea in 5 pts, for neutropenia in 4 pts, and for folliculitis in 1 pt. One patient was removed from study during week 6 for prolonged diarrhea/ dehydration. Due to the 2-step design of the trial, accrual is on hold pending a 3rd required pathologic CR in the first 17 patients. Conclusions: Compared to other trials of irinotecan, cisplatin, radiation therapy, and surgery in similar groups of esophageal cancer patients, early results for this combination with cetuximab suggest a lower complete response rate and higher overall toxicity. Additional data will be available at ASCO. Supported by Bristol-Myers Squibb. No significant financial relationships to disclose.
Phase II study evaluating trimodal therapy with cetuximab intensity modulated radiotherapy (IMRT) and gemcitabine for patients with locally advanced pancreatic cancer [ISRCTN56652283]
Authors: Krempien R. C. , Münter M. W. , Timke C. , Huber P. E. , Friess H. , Heeger S. , Herfarth K. K. , Abdollahi A. , Hartung G. , Buchler M. W. , Debus J. 
Published: March 2020

4100 Background: The induction of EGFR targeting with cetuximab in radiation based therapy of solid tumors has yielded promising results. Thus, we initiated a prospective Phase II trial designed to analyze the feasibility and effectivity of trimodal therapy with gemcitabine-based chemoradiation and cetuximab in locally advanced inoperable pancreatic cancer. Methods: In this phase 2 study, pts with locally advanced pancreatic cancer without prior cytotoxic therapy were treated with radiotherapy (RT), gemcitabine weekly (300 mg/m2), and cetuximab weekly (loading dose 400 mg/m2 day 1, and concomitant with radiation day 8,15,22,29,36 250 mg/m2). RT was delivered by using an integrated IMRT boost concept (54 Gy GTV, 45 Gy CTV) over 5 weeks. RT was followed by gemcitabine (1000 mg/m2) weekly × 3 in 4 weeks. Response evaluation using computed tomography followed at week 12. All amenable patients were intended for surgical treatment between week 12–15. Results: 24 pts were enrolled until now. Preliminary results are presented on 20 pts with the following characteristics: pancreatic adenocarcinoma c2 T4 N1 20/20, median age = 63.5 (range 51–79); M/F = 13/7; ECOG PS 0/1/2 = 2/12/6; median days on treatment: 90 (range 70–100). Treatment-related toxicities were observed in 16 pts. Grade 3 toxicities included diarrhea (n = 4), fatigue (n = 2), nausea (n = 3), neutropenia (n = 6), thrombocytopenia (n = 2), and vomiting (n = 2). 18/20 pts developed some acneiforme rush during therapy. No omittance of cetuximab therapy was necessary. 1 patient died during RT due to tumor bleeding. Median follow-up at present is 6 month, median survival has not been reached. Partial remissions 8/20, stable disease 9/20, progressive disease 3/20. 12/20 patients were amenable for secondary potentially curative resection. 4 patients could be resected, while 3 patients were found to have abdominal metastatic spread. Conclusions: Early data from trimodal therapy in pancreatic adenocarcinoma with chemoradiation (IMRT), gemcitabine, and cetuximab indicate feasibility without increased toxicity profile. The local response appears to be very promising in pancreatic cancer, potentially allowing neoadjuvant treatment. [Table: see text]
Combined modality therapy for pancreatic carcinoma: An Australian Pancreatic Cancer Group study of the addition of gemcitabine (G) to concurrent infusional 5-fluorouracil (CI 5FU) and 3D conformal radiotherapy (RT)—Final outcomes
Authors: Goldstein D. , Spry N. , Van Hazel G. , Underhill C. , Kotasek D. , Harvey J. , Links M. , Shapiro J. , Iacopetta B. , Australia Eli Lilly 
Published: March 2020

4104 Background: This open-label Phase II study (B9E-AY-S168) examined whether CI 5FU plus 3D conformal planning RT is well tolerated and may be combined with G pre and post chemoradiotherapy in patients (pts) with pancreatic cancer (PC). Methods: Eligible pts were enrolled in two strata: (1) inoperable PC in head or body without metastases (LAD) or (2) resected PC at high risk of relapse (Surg). G was given at 1000 mg/m2 weekly for 3 wks followed by 1 wk rest and a 5–6 wk period of RT and concurrent CI 5FU (200 mg/m2/day). The defined target volume was treated to 54Gy in 30# of 1.8Gy (LAD) or 45Gy in 25# (Surg). After 4 wks rest, G was given for 12 wks. Results: 63 pts were enrolled: 39 females, 24 males; mean age 61 yr, range 31–79; 43% ECOG PS 0, 51% PS 1, 5% PS 2. Follow-up was 2 yr. 1- and 2-yr survival (KM) were 46% and 10% (LAD) and 59% and 27% (Surg). 1- and 2-yr local control (KM) were 48% and 21% (LAD) and 80% and 80% (Surg). The % planned dose delivered was (i) G pre RT: 87.6% (LAD)/94.6% (Surg); (ii) 5FU: 100.7%/96.4%; (iii) RT: 96.2%/99.5%; (iv) G post RT: 67.4%/65.3%. The baseline CA 19.9 level was significantly associated with a shorter TTPD (p=0.0002) and a shorter survival time (p=0.0071). Using Time Dependent Covariate analysis, CA 19.9 levels were strongly associated with TTPD and survival (both p < 0.0001); a person with a 10-fold higher level has a 1.95-fold higher risk of death over the next time period than their counterpart (95% CI: 1.53–2.49-fold). In 22 pts we found no statistically significant associations between outcome and mutations in K-RAS or TP53 or with microsatellite instability. Grade 3/4 hematological and non-hematological toxicity was reported by 29 (46%) and 42 pts (67%), respectively. There was one treatment-related death. Conclusions: This approach to treatment is safe and promising, with good local control for a substantial proportion of patients, and merits testing in a randomized trial. [Table: see text] [Table: see text]
Phase I study of oral fluoropyrimidine anticancer agent (S-1) with concurrent external-beam radiotherapy for unresectable pancreatic cancer
Authors: Shinchi H. , Takao S. , Maemura K. , Noma H. , Aikou T. 
Published: March 2020

4109 Background: S-1 is an oral fluorouracil anticancer agent that was recently reported to demonstrate a response rate of 21% in 19 patients with advanced pancreatic cancer. Concurrent external-beam radiotherapy (EBRT) and 5-FU has been generally accepted as the standard treatment for locally advanced pancreatic cancer. However, there are no published data regarding the efficacy of combination therapy of S-1 and radiation in patients with pancreatic cancer. Our purpose of this study was to evaluate the safety of S-1 combined with EBRT and determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of S-1 in patients with locally advanced and unresectable pancreatic cancer. Methods: Eligible patients had UICC stage III or IV pancreatic cancer (either advanced unresectable or metastatic), adequate organ function, and no anticancer therapy in the preceding 4 weeks. S-1 was given orally at a dose of 60 mg/m2/day or 80 mg/m2/day in two divided doses after breakfast and supper. External-beam radiotherapy was delivered using a conformal technique in fraction of 1.25 Gy X 2/day, 5 days per week, totaling 50 Gy/40 fraction for 4weeks. S-1 at a dose of 60 mg/m2/day was given on days 1–7 and 15–21 in level 1, on days 1–14 in level 2, on days 1–21 in level 3a, respectively. S-1 at a dose of 80 mg/m2/day was given on days 1–21 in level 3b and on days 1–28 in level 4. DLT was defined as NCI-CTC grade 3/4 toxicity. Results: 18 patients were entered in this phase I trial: level 1 (4 patients), level 2 (5 patients), level 3a (3 patients), level 3b (3 patients), level 4 (3 patients). There were 1 of 5 patients with DLT in level 2: grade 3 vomiting. There were no DLT in levels 1, 3a, and 3b, respectively. Two of 3 patients in level 4 showed DLT: one patient developed grade 3 neutropenia and another patient developed grade 3 diarrhea. Clinical effects by CT scan included one PR, 15 SD and 2 PD. Reduced CA19–9 level less than a half of that at starting time was observed in 6 of 18 patients. Conclusions: S-1 at a dose of 80 mg/m2/day given on days 1–21 is safe and may be recommended for phase II study in patients with locally advanced and unresectable pancreatic cancer. This regimen appears to be a promising and well-tolerated approach with consideration of application to outpatients. No significant financial relationships to disclose.
Phase II study of volociximab (M200), an α5β1 anti-integrin antibody in metastatic adenocarcinoma of the pancreas (MPC)
Authors: Valle J. W. , Ramanathan R. K. , Glynne-Jones R. , Anthoney A. , Berlin J. , Yazji S. , Evans T. 
Published: March 2020

4111 Background: Tumor angiogenesis occurs when pro-angiogenic growth factors are released, stimulating endothelial cell proliferation and migration to form neovessels. A critical survival step for angiogenesis is the ligation of fibronectin in the extracellular matrix to α5β1 on endothelial cells. M200 is an IgG4 chimeric monoclonal antibody targeting α5β1, thereby inducing apoptosis of proliferating endothelial cells. M200 activity is independent of growth factor stimulus, suggesting that binding of fibronectin to α5β1 occurs downstream of growth factor signalling, and is possibly a final common pathway for the development of neovasculature. Methods: This is a multicenter, open label, single cohort pilot Phase II study of 40 patients (pts) in MPC. Pts received M200 10 mg/kg IV every 2 weeks with Gemcitabine (Gem) 3 weeks on 1 week off for up to 13 cycles or disease progression. Pts were evaluated for efficacy every 8 weeks by objective response using RECIST criteria. An independent data safety monitoring board was utilized to review safety data. Results: A total of 20 pts have been enrolled. All pts were evaluable for safety and 16 pts for objective response (to date) using ITT population. Median age was 59.8 years. ECOG score was 0–1 in 19 (95%) and 2 in 1 (5%) pts. The most frequent side effects for M200 were vomiting in 7 (35%) pts and nausea in 8 (40%) pts and for (Gem) were nausea in 8 (40%) pts and vomiting in 8 (40%) pts. Eight pts died in the study, seven with progressive disease and 1 with GI perforation (possibly related to M200). One partial response was noted to date. Best overall response was (PR) 1/16 and stable disease in 8/16 pts. Median time to progression was 112+ days. Conclusions: M200 appears to be well tolerated at 10 mg/kg Q2W in combination with (Gem). Based on preliminary data from this trial and safety data from other trials, a higher dose level of M200 will be explored. [Table: see text]
A randomized phase II study comparing gemcitabine plus nadroparine versus gemcitabine in patients with locally advanced or metastatic pancreatic carcinoma: The GEMFRAX trial
Authors: Voorthuizen T. V. , Vervenne W. L. , Van Daalen E. H. , Phoa S. S. , Gouma D. J. , Bruno M. J. , Richel D. J. 
Published: March 2020

4112 Background: Gemcitabine is considered to be the standard chemotherapy regimen for advanced pancreatic cancer. The advantage of gemcitabine over best supportive care however is limited. Preclinical and clinical data have shown that low molecular weight heparin (LMWH) has an inhibitory effect on tumor progression. Two years ago provoking and promising results were presented at ASCO in a pancreatic cancer population. In this study we wanted to confirm these promising results, in which 6-month survival was the primary endpoint. Methods: Patients (pts) with advanced pancreatic carcinoma were randomized to either gemcitabine 1000 mg/m2 on day 1, 8 and 15 every 4 weeks (arm A) or gemcitabine plus nadroparine 5700 IU twice daily from day 1 to 21 every 4 weeks (arm B). Simon’s optimal two-stage design was applied to each arm to assess the treatment efficacy within each arm. This design required to enter 10 pts in the experimental arm in the first stage with the hypothesis that 70% instead of the expected 45% would be alive at 6 months. If 5 or less pts were alive at 6 months, the trial would be stopped and the regimen would be declared as ineffective. Results: 27 pts, all with metastatic disease, have been enrolled to date, 16 in arm A and 11 in arm B. Of the first 10 pts in the experimental arm only 4 were alive at 6 months (arm A: 6 of 10 pts alive).The median overall survival (OS) of these pts was 5.6 months and the median progression free survival (PFS) was 4.1 months (in arm A 8.7 and 5.1 months, respectively). The best response was stable disease (80%). No bleeding complications were seen. Conclusions: This small sized study was designed to detect a large, clinically relevant, difference in 6-month survival in pts with advanced pancreatic cancer treated with a combination of gemcitabine plus nadroparine compared to gemcitabine alone. Adding nadroparine to gemcitabine was feasible and gave no serious toxicity attributable to nadroparine. According to Simon’s two-step design a planned analysis after entering 10 pts in the experimental arm rejected the assumption that the combination induced an absolute increase in 6-month survival of 25% (5% type I error rate and 80% power). No significant financial relationships to disclose.