bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidermal growth factor receptor (EGFR) serum level may predict response in patients with advanced colorectal cancer (ACC) treated with gefitinib
Authors: Zampino M. G. , Magni E. , Zorzino L. , Santoro L. , Massacesi C. , Zaniboni A. , Di Clemente F. , Martignetti A. , Boselli S. , de Braud F. 
Published: March 2020

4119 Background: EGFR-overexpression reported in colorectal cancer, justifies use of EGFR inhibitors. We conducted a phase II study (ESMO 2005) in ACC with the aim to assess efficacy of gefitinib plus oxaliplatin containing regimen. Main biological objective was to assess serum EGFR extra-cellular binding domain as surrogate marker of tyrosine-kinase inhibition and as predictor of outcome. Methods: 57 patients with EGFR-positive ACC,received gefitinib 250 mg/day combined with simplified FOLFOX-6 for at least 4 cycles,for a maximum of 10 courses.In not progressive disease, gefitinib was continued as maintenance treatment. Tumour assessment by RECIST criteria was performed at baseline and every 4 cycles.Serum EGFR extracellular binding-domain was evaluated by quantitative enzyme-linked immunoadsorbent.Serum EGFR as predictive factor was evaluated both taking into account the basal value only,and the whole EGFR pattern over time.The analyses were performed by logistic and Cox’s regression model with time-dependent covariate respectively;both models included centre, gender,age and site of primary tumours as adjusting factors. Results: Serum samples for EGFR were obtained at baseline and at every assessment.During mono-therapy phase the patients with serum samples decreased. Over treatment,34 patients reported a CR or PR as best objective response (BOR),while 9 patients showed SD or PD. Higher serum EGFR was associated to BOR both at baseline and over time.This result was confirmed by a similar analysis,which considered the whole EGFR profile,instead of the basal value only. Conclusions: Serum EGFR at baseline can be considered a significant predictor for the BOR.This observation is in line with data reported on lung cancer (Gregorc V, 2004).Although the EGFR trend over time seems to confirm the basal difference,this result should be taken with caution,due to the little number of cases reporting EGFR values besides the basal one. [Table: see text] No significant financial relationships to disclose.
A phase II study of preoperative chemotherapy with irinotecan(CPT) and cisplatin(CIS) for gastric cancer(NCI 5917): FDG-PET/CT predicts patient outcome
Authors: Shah M. A. , Yeung H. , Coit D. , Trocola R. , Ilson D. , Randazzo J. , Tang L. , Brennan M. , Divgi C. , Kelsen D. P. 
Published: March 2020

4502 Introduction: Preoperative chemotherapy is a standard option for the treatment of locally advanced gastric cancer(GC). FDG-PET scans have been examined to identify early treatment response in esophagus and GEJ adenocarcinoma. We evaluated the utility of an early change in FDG-PET/CT at several time points in predicting response to preoperative chemotherapy in gastric cancer. Methods: 42 pts with locally advanced GC(preoperative stage T2N+M0 or T3–4NanyM0) were treated with CPT 65 mg/m2 and CIS 30mg/m2 on day(d)1 and d8, every 21 days for 4 cycles. FDG-PET/CT scans were performed at baseline, and in FDG avid patients, again on d15 and d35. The primary objective was to demonstrate that a decrease in FDG-SUV discriminates treatment response. Response was defined pathologically based on microscopic inspection for residual cancer cells and fibrosis(Mandard, Cancer 1994). Disease free survival(DFS) and overall survival(OS) were secondary endpoints. Results: Pt characteristics are as follows: median age 59(35–77), KPS 90%(70–100%), 27 male, gastric:GEJ 31:11. Median follow up is 23.3 months, with median DFS 23.8 months(95%CI 14-infinity) and median OS 39.1 months(95%CI 31–39months). Surgical resection occurred at a median of 101 days from study initiation. Pathologic response correlates significantly with DFS(p=0.005) and with OS(p=0.01). Amongst 31 FDG avid pts, a drop in SUV from baseline to d35 significantly predicts pathologic response(p=0.007) and DFS(p=0.01), whereas the change at d15 does not. 45% decrease in SUV at d35 best distinguishes good from poor pathologic response. With this cutoff, median DFS has not been reached(eg.>23.3 months) for patients with good PET response, and is 14.4 months(95%CI 8.3-infinity) for poor PET responders, p=0.03. Conclusions: Following preoperative chemotherapy, pathologic response at the time of resection significantly correlates with DFS and OS. We confirm that FDG-PET/CT response predicts both pathologic response and DFS following preoperative chemotherapy for locally advanced GC, although at d35. An early PET response assessment provides an opportunity to change therapy in non responding patients, and is currently under investigation(supported by ASCO CDA). No significant financial relationships to disclose.
A double-blind, placebo-controlled, randomized phase III trial of gemcitabine (G) plus bevacizumab (B) versus gemcitabine plus placebo (P) in patients (pts) with advanced pancreatic cancer (PC): A preliminary analysis of Cancer and Leukemia Group B (CALGB
Authors: Kindler H. L. , Niedzwiecki D. , Hollis D. , Oraefo E. , Schrag D. , Hurwitz H. , McLeod H. L. , Mulcahy M. F. , Schilsky R. L. , Goldberg R. M. 
Published: March 2020

4508 Background: In a phase II trial in 52 PC pts, GB yielded a 21% response rate and a median survival of 8.8 months (mo) (Kindler, JCO 2005). These data led CALGB to conduct a phase III trial of GB vs. GP in advanced PC pts. Methods: This randomized trial was double-blind, placebo-controlled. Eligible pts had no prior therapy for advanced disease, PS 0–2, no tumor invasion of adjacent organs, no increased bleeding risk. Primary endpoint: overall survival (OS). Stratification: PS (0/1 or 2), disease extent (locally advanced or metastatic), prior radiation (RT) (yes/no). Statistics: 90% power to detect a difference in median OS of 6 vs. 8.1 mo. Treatment: Pts received G 1,000 mg/m2 over 30 minutes days (D) 1, 8, 15 Q28D; B 10 mg/kg or P D 1, 15 Q28D. CT scans: Q2 cycles. Results: 602 pts enrolled 6/30/04–4/14/06. Based on a protocol-specified interim analysis with 64% of information on OS, the CALGB Data Safety Monitoring Board released study data in 6/06 because a futility boundary was crossed. Pts on treatment were notified and unblinded. Pt characteristics (302GB/300GP): male 58%/51%; median age 63.8/65.0; PS 2 9%/9%; stage IV 85%/84%; prior RT 11%/11%. Median follow-up: 11.3/11.7 mo. As of 12/22/06, 436 pts (224/212) have died (93% of total expected deaths at planned final analysis). Median OS 5.7/6.0 mo (95% CI: 4.9, 6.5/5.0, 6.9). Median failure-free survival 4.8/4.3 mo (95% CI: 4.3, 5.7/3.8, 5.6). Response (includes unconfirmed responses): complete (CR) 1.9%/3.0%; partial (PR) 11.2%/8.3%, stable disease (SD) 40.7%/35.7%. Disease control rate (CR/PR/SD) 54%/47%. 525 pts (268/257) are currently evaluable for toxicity. Median cycles 3.5/3.1 (p=0.09). Total mg/m2 G received 9095/8334 (p=0.22). Grade ¾ toxicity (%pts GB/GP): neutropenia 33%/30%; anemia 5%/8%; thrombocytopenia 12%/12%; hypertension 8%/2%; perforation 0.4%/0%; GI bleed 3%/2%; CVA 2%/2%; proteinuria 4%/1%; venous thrombosis 9%/9%. Conclusion: The addition of B to G does not improve survival in advanced PC. [Table: see text]
Combination of endoscopic mucosal resection and chemoradiotherapy as a nonsurgical treatments for patients with clinical stage I esophageal squamous cell carcinoma
Authors: Minashi K. , Ohtsu A. , Mera K. , Muto M. , Yano T. , Tahara M. , Doi T. , Nishimura M. , Nihei K. 
Published: March 2020

4529 Background: Endoscopic mucosal resection (EMR) has become the standard treatment for mucosal cancer. For the other clinical stage I esophageal squamous cell carcinoma (ESCC), radical surgery is standard and chemoradiotherapy (CRT) is optional but has high locoreginoal failure. If EMR and CRT are combined efficiently, these may improve outcomes with less invasion. A retrospective analysis was conducted to evaluate the efficacy of these combined nonsurgical modalities. Methods: Recruitment criteria were histologically proven SCC, clinically estimated as stage I except for the candidates of the standard EMR, age ≤ 75, PS ≤ 2, no prior therapy, no serious complication and no other active malignancy. Primary EMR was indicated if a tumor was within the focal submucosal (SM) invasion and a width of less than two-thirds of its circumference. EMR was followed by prophylactic CRT (5-FU + cisplatin + RT; 40Gy) for latent node metastasis when SM invasion was present pathologically. The remaining patients (pts) underwent primary CRT (5-FU + cisplatin + RT; 60Gy); salvage EMR was indicated for local residual, recurrent, or metachronous tumors. Results: Between Jan. 1996 and Apr. 2004, 86 pts fulfilled the criteria; median age 60 years (46–75), male/female; 74/12. Forty-one received primary EMR and 45 received primary CRT. Pathological diagnoses of primary EMR revealed eight mucosal cancers of the epithelium and lamina propria, 19 of the musclaris mucosae (MM), and 14 SM cancers. Eleven pts with SM cancers subsequently underwent prophylactic CRT, one with SM cancer underwent surgery, and the remaining 29 pts with mucosal and MM cancers received no additional treatment. Of the 45 CRT pts, 11 (24%) received salvage EMR. Three (3%) (one primary EMR pt and two primary CRT pts) underwent salvage surgery. With a median follow-up of 4.2 years, the 4-year overall survival of all, primary EMR, and primary CRT pts was 76%, 78%, and 72%, respectively; the disease-specific survival was 86%, 91%, and 81%, respectively. Conclusion: The survival of combination treatment with EMR and CRT for clinical stage I ESCC was comparable with that of surgery in Japan. EMR and/or CRT may be highly effective, minimally invasive treatments for stage I ESCC. No significant financial relationships to disclose.
Multi-centre prospective assessment of accuracy and impact on management of positron emission tomography (PET) in esophageal and gastroesophageal junction cancers (EC). Australian PET Data Collection Project
Authors: Chatterton B. E. , Ho-Shon I. , Lenzo N. , Patrikeos A. , Kelley B. , Baldey A. , Ramshaw J. , Scott A. 
Published: March 2020

4534 Background: In localized EC, radical surgery may be curative. This study evaluated PET and conventional imaging techniques (CI) for staging, and the potential impact of PET on management and prognosis of EC. Methods: Subjects had confirmed EC (SCC or adenocarcinoma), were fit for investigation and surgery and/or chemoradiotherapy and had no unequivocal distant metastatic disease clinically or by CT and endoscopy at presentation. Sensitivity, including N and M staging of pre-operative CT, PET and endoscopic ultrasound (EUS) and clinical impact of confirmation or detection of metastases on intent (curative or palliative) were recorded. Management changes, including radiotherapy field determined by new information from PET, were recorded. Variables, including standardized uptake value (SUV) were compared with progression-free survival (PFS.) Results: 129 patients (104 male), mean age 66 (range 36- 87) were evaluated. 127 of 129 primary lesions were detected. In 41% of patients, PET detected a total of 148 additional lesions, 75 regional lymph nodes, 72 distant metastases and 1 second EC primary. 22% of patients were upstaged from M0 to M1. CT detected regional and distant metastases in 57% and 0% (entry criterion), PET in 70% and 44%. Of 20 patients who had EUS, it detected regional metastases in 67%, PET in 33%.The number of patients intended to be treated palliatively increased from 10 pre- to 32 post-PET. Of patients with curative management intent based on PET 34% progressed in 12 months, with palliative intent 59%. Significant changes in management (high or medium impact) occurred in 38%. The PFS of 54 patients below and 54 above the median SUV(8) was no different (p=0.79) Conclusions: PET influenced management in 38% of patients with EC already studied by CI. No significant financial relationships to disclose.
Molecular detection of occult nodal metastases in esophageal adenocarcinoma
Authors: Altomare I. , Pennathur A. , Xi L. , Gooding W. E. , Litle V. R. , Luketich J. D. , Godfrey T. E. 
Published: March 2020

4540 Introduction: Esophageal adenocarcinoma (EAC) is an aggressive malignancy whose incidence is on the rise. Approximately 40% of patients with N0 disease will recur after theoretically curative surgery, suggesting that in early stage disease, metastatic spread is often undetected by routine pathology. Molecular techniques may more accurately detect micrometastatic spread of EAC, but the correlation between molecular analysis of nodes and prognosis is unknown. Our lab has previously identified and validated 4 markers whose gene expression levels are able to distinguish benign nodes from nodes with metastatic EAC: CK19, CK20, CEA and TACSTD1. We used quantitative real-time RT-PCR to evaluate the expression of these 4 markers in lymph nodes from 68 N0 and 62 N1 EAC patients to see if molecular staging is predictive of a worse clinical outcome. Methods: RNA was isolated from 1456 lymph nodes obtained from 130 patients who underwent resection of EAC. QRT-PCR was used to analyze gene expression for each of the 4 markers. Relative expression of each marker was compared with expression in 53 benign esophageal lymph nodes previously analyzed. Results: Analysis of 778 lymph nodes from 68 pN0 patients identified 71 nodes (9%) from 30 patients (44%) which showed positive expression of at least one marker, indicating occult metastases (and molecular upstaging). Analysis of 678 lymph nodes from 62 pN1 patients revealed 141 nodes (21%) from 40 patients (65%) which had positive expression of at least one marker in nodes that were pathologically negative. In the pathologically positive nodes from N1 patients, there was an encouraging 88% concordance between pathological and molecular analysis. After a median follow-up of 2 years, 13 N0 patients had recurrence of their cancer. Gene expression levels of 3 of the 4 markers (CK20, CEA and TACSTD1) correlated with significantly worse disease-free and overall survival among these N0 patients, with p values <0.05. Conclusion: We have shown that QRT-PCR of 3 independent genetic markers is predictive of significantly worse disease-free and overall survival among node-negative EAC patients by identifying lymph nodes with occult metastatic disease. Further analysis will reveal if the N1 patients with molecularly positive lymph nodes had significantly worse outcomes as well. No significant financial relationships to disclose.
The impact of cetuximab on the gemcitabine/cisplatin combination in first-line treatment of EGFR-positive advanced pancreatic cancer (APC): A randomized phase II trial of GISCAD
Authors: Cascinu S. , Berardi R. , Siena S. , Labianca R. , Falcone A. , Aitini E. , Barni S. , Di Costanzo F. , Frontini L. , Tonini G. , Zaniboni A. 
Published: March 2020

4544 Background: Cetuximab, an EGFR antibody inhibitor, has been shown to increase the activity of gemcitabine (GEM) in APC. Based on data from randomised trials and meta-analyses suggesting that the combination of a GEM with a platinum analog significantly improves survival as compared to GEM alone, we assessed the activity and feasibility of a combination of GEM/cisplatin (CDDP) plus cetuximab. Methods: Multicenter, randomised two-arm phase II trial: GEM 1,000 mg/m2 day 1,8 and CDDP 35 mg/m2 day 1,8 every 21 days alone or in combination with cetuximab 250 mg/m2 weekly after a loading dose of 400 mg/m2. Treatment was limited to a maximum of 9 cycles. With 37 patients in each arm the power was 90% to select the truly better arm if the true between arm difference in response rate (RECIST) is at least 15%. The study was open for accrual until June 2005. Results: We present here the results of 74 patients including in the study. In all the patients, the first response rate are available (investigators’ assessment after 3 cycles) as well as toxicity data. Conclusions: Cetuximab does not seem to positively interact with GEM/CDDP combination in terms of activity especially concerning time to progression. Although toxicity was not increased by cetuximab, this combination should not be assessed in a phase III trial.The trial was supported in part by by Merck KGaA. [Table: see text] No significant financial relationships to disclose.
Sentinel node mapping for esophageal cancer
Authors: Takeuchi H. , Kitagawa Y. , Saikawa Y. , Suto A. , Mukai M. , Nakahara T. , Kubo A. , Kitajima M. 
Published: March 2020

4552 Background: Extended radical esophagectomy with three-field lymph node dissection has been recognized as a standard procedure for esophageal cancer in Japan, even for clinically node negative cases. However, a significant increase of morbidity and mortality after the invasive procedure was reported in randomized trials. To eliminate the uniform application of highly invasive surgery, we hypothesized that sentinel node (SN) mapping plays a key role to obtain individual information and allows modification of the surgical procedure for early esophageal cancer. Methods: We have established radio-guided method to detect SNs in patient with early esophageal cancer using endoscopic injection of technetium-99m tin colloid. Preoperative lymphoscintigraphy and intra-operative use of hand held gamma probe were reliable to locate the radioactive SNs. Intra-operative gamma probing was also feasible in thoracoscopic or laparoscopic surgery using a special gamma detector which is introducible from trocar ports. Results: SN mapping has been performed for 105 patients with clinically N0 early esophageal cancer in our institute since 1999. Detection rate of hot node using our procedure was 93% (98/105). The mean number of sentinel nodes per case was 5.1. Thirty-three of 37 cases with lymph node metastasis showed positive sentinel nodes. The sensitivity to detect metastasis based on SN status was therefore 89% in our experience. Accuracy of metastatic status based on SN was 96% (94/98). SNs widely spread from cervical to abdominal areas. In more than 80% of the cases, at least one SN was located in the 2nd or 3rd compartment of regional lymph nodes. Conclusions: Our results suggest that SN concept for clinically N0 early esophageal cancer could be validated, and individualized selective and modified lymphadenectomy targeted on sentinel node basins for clinically N0 early esophageal cancer should become feasible and clinically useful as less invasive surgical procedures. No significant financial relationships to disclose.
Polymorphisms of the serotonin transporter and Monoamine Oxidase A gene in patients with metastatic midgut carcinoid tumors
Authors: van der Horst-Schrivers A. , de Vries E. , Willemse P. , Kema I. , Links T. , Boezen H. , Wymenga A. 
Published: March 2020

4557 Background: In patients with metastatic midgut carcinoid tumors increased serotonin secretion is related to the carcinoid syndrome and mortality. Free serotonin is taken up via the serotonin transporter (5-HTT) in the liver and the lung and metabolized to 5- hydroxyindolacetic acid (5-HIAA) by Monoamine Oxidase A (MAO-A). The 5-HTT gene has a functional polymorphism in the promoter region (5-HTTPLR), with a short (S, less active) and long (L) allele and a polymorphic region in the second intron with variable number tandem repeats (VNTR-2). The MAO-A gene contains a length polymorphism in its promoter region (MAOA-LPR). To determine the clinical effects of the serotonin metabolizing capacity of individual patients, the association between different genotypes and symptoms (flushes and diarrhea) and survival was studied. Methods: 107 patients with metastatic midgut carcinoid tumors were genotyped for 5-HTTPLR, VNTR-2 and MAO-A-LPR. Differences were tested using Chi-square test and survival according to genotypes was analyzed using Kaplan Meier survival curves and tested with a log rank test. The independent effect of genotypes on survival was studied with multivariate Cox regression analysis with adjustments for the urinary 5-HIAA level, age at presentation and the presence of liver metastases. Results: The various genotypic variants were not related to flushes or diarrhea. Patients with the SS variant of 5-HTTLPR had a shorter median survival (45 months, 95% Confidence Interval (CI) 0.50–90) compared to patients with the LS (113 months, 95% CI 53–172) and the LL variant (90 months, 95% CI 64–115) (P=0.02). After adjustment, survival in patients with the SS variant remained worse with an odds ratio of 0.43 (95% CI 0.23–0.83; P=0.009) and 0.63 (95% CI 0.33–1.11; P=0.1) compared to patients with the LS and the LL variant respectively. Survival was not influenced by the VNTR-2 or MAOA-LPR. Conclusions: The SS genotype of the 5-HTTLPR is independently associated with a worse survival in patients with metastatic midgut carcinoid tumors. No significant financial relationships to disclose.
Biweekly oxaliplatin with gemcitabine and capecitabine in advanced gastrointestinal malignancies: A phase I study
Authors: Tan B. R. , Brenner W. S. , Picus J. , Suresh R. , Sorcher S. , James J. S. , Fournier C. , Mcleod H. L. 
Published: March 2020

4560 Background: Oxaliplatin (OX), gemcitabine (GEM) and capecitabine (CAP) are all active agents against various gastrointestinal and other malignancies and have different mechanisms of action and toxicity profiles. This Phase I study aims to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) associated with this triplet regimen. Methods: The modified Fibonacchi 3/cohort dose escalation schema was used to determine the MTD and DLT of OX, GEM and CAP. Oxalipaltin [85–100 mg/m2] IV over 2 hours and gemcitabine [800–1,000 mg/m2] were given at a constant rate infusion of 10 mg/m2/min on days 1 & 15, while CAP [600–800 mg/m2] was given PO BID on days 1–7 and 15–21. 1 cycle = 28 days. Pharmacogenomic correlates including ERCC2, GSTP1, TYMS, TS del and TSER G>C were also obtained. A structured neurological toxicity assessment and questionnaire was also performed. Once MTD was established, additional patients were treated at the MTD and pharmacokinetic studies were performed on these additional patients. Results: 30 patients (M:F 2:1; 23% non-caucasian) with median age of 62 (range: 38–78) and PS of 0–1 were enrolled from 3/05 to 8/06. All patients had advanced GI malignancies (19 pancreatic, 6 biliary, 2 duodenal, 1 gastric, 1 esophageal, 1 GI unknown primary). Dose levels, # patients, DLT and best responses are tabulated below. Conclusions: The MTD of this triplet regimen is OX at 100 mg/m2, GEM at 800 mg/m2 days 1 & 15 with CAP at 800 mg/m2 PO BID days 1–7, 15–21. DLTs for this regimen include grade 3 fatigue and dyspnea as well as Grade 4 thrombocytopenia. CR is achieved in 2 patients (cholangiocarcinoma and pancreatic), while a patient with a GI unknown primary achieved PR. Several patients with pancreatic cancer achieved prolonged SD. An exploration of any association of toxicities and response with pharmacogenomic correlates is ongoing. A Phase II study in patients with pancreaticobiliary cancers is planned. This study is supported by Sanofi-Aventis Pharmaceuticals. [Table: see text] [Table: see text]