bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic impact of response to second-line chemotherapy on overall survival of patients with advanced gastric cancer
Authors: Kim S. , Hwang M. , Park Y. , Park S. , Kim Y. , Ryu K. , Lee J. , Park Y. , Kim N. , Park S. 
Published: August 2020

e15551 Background: It has been debated on whether tumor response to first-line chemotherapy (CT) would be reliable predictor for overall survival (OS) of cancer patients (pts). In case of advanced gastric cancer (AGC), many pts receive 2nd line CT after failure to 1st line treatment, so response to 2nd line CT as well as 1st line could affect OS. Methods: We retrieved clinical data of a total of 1,335 pts with AGC treated with palliative CT from January 2000 to December 2006 in National Cancer Center, Korea, including 757 pts who also received 2nd line CT. Responses to 1st and 2nd line CT were evaluable in 504 pts. Retrospective analysis was done to find correlation between objective tumor response to 1st and 2nd line CT and OS of the 504 pts, whom we divided into 4 groups: responders to both 1st and 2nd line CT (RR group); responders to 1st but not to 2nd line CT (RN group); responders to 2nd but not to 1st line CT (NR group); and nonresponders to both 1st and 2nd line CT (NN group). Results: Objective response rate of 1st and 2nd line CT was 41.7% and 12.3%, respectively. Responders to 1st line CT had a trend to respond to 2nd line CT (ORR of 2nd line CT in responders vs nonresponders to 1st line CT: 15.7% vs 9.9%, p = 0.049). 33/177/29/265 pts were assigned to each of RR/RN/NR/NN group, respectively. With median follow-up of 48.7 mo (range 23.2 - 93.7), median OS was 12.7 mo (95% CI 11.8–13.6). Baseline characteristics were balanced between 4 groups except higher hemoglobin and serum albumin level in RR group, younger median age in NN group, and fewer pts with poor performance status or poorly differentiated histology in NR group. Overall survival of RR, RN, NR, and NN group was 31.8 mo, 15.5 mo, 18.9 mo, and 9.2 mo, respectively (p<0.001). Multivariate analysis revealed relapsed disease after curative surgery, well-differentiated histology, absence of pulmonary metastasis, higher serum albumin level, lower serum bilirubin and alkaline phosphatase level, response to both of 1st line and 2nd line CT were reliable factors for favorable survival. Conclusions: Among the patients who received 2nd line chemotherapy for AGC, response to 2nd line CT was strongly associated with OS regardless of previous response to 1st line CT. No significant financial relationships to disclose.
Effect of hospitals on survival and postoperative mortality of stomach cancer: A population-based study on type, referral, and volume-effect in the northeast Netherlands
Authors: Siemerink E. , Schaapveld M. , Hospers G. A. , Mulder N. H. , Plukker J. T. 
Published: August 2020

e15564 Background: To optimize treatment results of patients with stomach cancer some institutions prompt referral to high volume hospitals with experienced surgeon's analogue to esophageal cancer. We analyzed if evidence can be found for superior treatment outcome depending on hospital type, referral pattern or hospital volume. Methods: Data from all patients diagnosed with primary invasive stomach cancer from 1994–2006 were obtained from the nationwide Netherlands Cancer Registry of the north-east part of the Netherlands. This area is served by one university hospital (U), 4 teaching hospitals (T), and 18 non-teaching hospitals (N-T). Results: In the study period, 5243 patients were diagnosed with stomach cancer (65.6% men, 34.4% female), 44.5% underwent surgery. Older age, advanced stage and proximal tumor location resulted in a lower probability of tumor resection. The 5 year relative survival (5yrsurv) was similar in the three hospital types. However, patients with proximal tumors were more often referred for surgery to U (18%), especially by N-T hospitals. In the non-proximal tumors the 5yrsurv was significantly better in U versus T and N-T hospitals, also after multivariate analysis. The significantly better 5yrsurv of low referral centers disappeared after excluding hospital U. No volume effect could be observed. Postoperative mortality registered in the period from 2004–2006 showed no differences between the hospitals. Conclusions: We found highly superior survival for non-proximal tumors but not for proximal cancer in an university hospital. In this study no evidence was found for a referral or volume effect. [Table: see text] No significant financial relationships to disclose.
Clinical outcome of endoscopic mucosal resection (EMR) in clinical stage I (cSt I ) esophageal cancer
Authors: Yoshii T. , Tamai S. , Aoyama N. , Minamide J. , Takagi S. , Motohashi O. , Nakayama N. , Nishimura K. , Takata K. , Kameda Y. 
Published: August 2020

e15569 Background: When a tumor invades to the muscularis mucosa or submucosal layer (T1a-MM or T1b, in Japan), cSt I esophageal cancer(EC) has 10–50%. risk of lymph node metastasis (LNM). Surgery, though very invasive, is the standard radical therapy for the patients(pts.) with such stage EC. Endoscopic mucosal resection (EMR), which conserves the esophagus, is a minimally invasive and attractive therapeutic modality for such pts. However, the clinical outcomes of EMR for these pts. have been not fully elucidated. Methods: We conducted retrospective analysis of the clinical courses of 44 pts. who underwent EMR for newly diagnosed T1a-MM or T1bcN0M0 EC between 1994 and 2007at our hospital, and who could be followed up for at least 1 year. Statistical analysis was performed by the Kaplan-Meier methods and the Cox proportional hazard model. Results: Patients decided on the following treatments immediately after EMR based on informed consent and their general condition; 2 underwent surgery, one underwent prophylactic chemotherapy(CHT) and 41 selected follow-up without any additional therapy. Of the 41, 20 selected this course by choice, 12 because of severe concurrent disease; 2 because of poor performance status and 7 because of other multiple primary cancers (MPCs). Twelve pts. died; 2 were cause specific; (4.5%), 8 from MPCs and, 2 from unknown causes. Median age was 67 years old (range 53–80), and 5 were female. No critical comlications were noted. Median follow-up time was 1542days (375–3786). 5 developed LNM. One with prophylactic CHT, was followed by surgery, and another was followed by CHT, who showed cause specific deaths later. Other 3 pts. followed by chemoradiotherapy, did not show cause specific death. Overall and cause specific survival rates at 5 years were 67.3% and 91.8%, respectively. Multivariate analysis revealed that either severe concurrent disease or MPCs significanctly influenced survival (p=0.041, HR 5.437(95%CI 1.073–25.542)). 8 and 6 pts. developed metachronous EC and local recurrence, respectively. Apart from one, they could be retreated endoscopicaly. Conclusions: EMR is a very useful therapeutic modality for cSt I EC, not only for local control but also as a clinically sufficient treatment; especially in pts. with severe concurrent disease. No significant financial relationships to disclose.
Safety and efficacy of single-day GemOx (S-GemOx) regimen in pts with pancreatobiliary cancer (PBC)
Authors: Merl M. Y. , Li J. , Lee M. X. , Saif M. W. 
Published: August 2020

e15577 Background: GemOx (G 1000 mg/m2 over 100 mins on d1 and Oxaliplatin (Ox) 100 mg/m2 on d2 q2 wks) achieved a RR of 26.8%, improved PFS but failed to demonstrate a benefit in OS vs G in PBC. This regimen has regained attention after recent pooled- and meta-analysis suggesting a survival benefit of G-platinum doublets over G. However, GemOx is associated with inconvenience to pts, early cumulative dose to develop neuropathy and thrombocytopenia. In addition, prolonged infusion of G showed no benefit over 30 mins in ECOG 6201study. Pharmacokinetic profile of both drugs did not show statistically significant differences regardless the order of administration. We modified GemOx as S-GemOx (G 1000 mg/m2 over 30 mins and Ox 85–100 mg/m2over 2 hrs on d1 q2 wks) given on same day to create a more convenient and equally effective regimen for these pts. Methods: A retrospective study was conducted to evaluate PBC pts who received S-GemOx from Sep 06 to Dec 08. Adverse events were graded according to NCI-CTC v3.0. Response was assessed with RECIST by a CT scan q 8 wks. Results: 34 pts (median age 60y, M/F: 17/17) who received S-GemOx were evaluated: PC (26), BC (7) and ampullary ca (1). 7 pts received S-GemOx plus a biological agent (3 bevacizumab, 3 cetuximab and 1 panitumumab). Median duration of therapy was 12 wks (r: 2–56). Median cumulative dose of Ox was 510mg/m2(r: 85–2380). 27 pts were evaluated for efficacy after initial staging: 1 (3.7%) CR, 4 (14.8%) PR, 18 (66.7%) SD and 4 (14.8%) PD. ORR (CR+PR) and ODC (CR+PR+SD) were 18.5% and 85.2% respectively. Median EFS, PFS and OS were 12, 16.7 and 37.6 wks respectively. 13 (38%) pts required Ox dose reduction due to toxicities (cytopenia, HSR, elevated LFTs and diarrhea). G3/4 hematological toxicities include anemia (8%), neutropenia (11%), thrombocytopenia (5%), N/V (3%), diarrhea (3%), HSR (14%) and neuropathy (3%). No deaths occurred due to therapy. 1 pt received a total of 1,025 mg/m2 of Ox on OPTIMOX approach. 9 pts discontinued therapy due to PD and 19 due to toxicities. Currently 4 pts are still receiving therapy. Conclusions: S-GemOx regimen provides convenient schedule, appears to be less toxic (G3/4 neuropathy: 3% vs 19.1%; thrombocytopenia 5% vs 14 %) and has comparable efficacy vs GemOx. Prospective studies of S-GemOx in a large pt population are warranted. [Table: see text]
Impact of first-line and second-line PFS definitions within a randomized phase III trial in patients (pts) with metastatic pancreatic adenocarcinoma (MPA)
Authors: Dahan L. , Methy N. , Seitz J. , Mitry E. , Ychou M. , Gasmi M. , Raoul J. , Mariette C. , Bedenne L. , Bonnetain F. 
Published: August 2020

e15583 Background: The FFCD phase III trial in pts with MPA comparing LV5FU2-P followed by gemcitabine (arm A) versus the opposite sequence (arm B) had failed to demonstrate a significant difference in median OS and PFS. The aim of this ancillary study was to investigate definitions of 1st and 2nd line PFS and their impacts on results. Methods: From 08/2003 to 05/2006, 202 pts with measurable MPA, PS 0–2, non prior CT were included in 33 centers, 102 in arm A and 100 in arm B. PFS1 in 1st line was defined as time interval between randomization and progression (P) or death (D) during the 1st line. Alive patients without P have been censored at the beginning of 2nd line or at the last FU. PFS2 in 2nd line was defined as time interval between randomization and P or D during the 2nd line. Alive patients without P during 2nd line have been censored at the last FU. For patients receiving only one line, PFS2 was defined as time interval between randomization and first P or D. Survival curves has been estimated using Kaplan Meier and compared using log-rank Tests. Strict ITT and modified ITT (ie pts receiving 2 lines) analyses were performed Results: Amongst the 202 pts after a median follow-up of 44 months, 69 pts (45 pts due to P) in Arm A and 55 pts (48 pts due to P) in Arm B have received a 2nd line. Median PFS was respectively equal to 3.4 months in Arm A and 3.5 months in Arm B (Stratified Log-Rank p = 0.78). For PFS1 we observed 77 and 93 events respectively in Arm A and B. Median PFS1 was equal to 4.0 months in Arm A and 3.5 months in Arm B (Stratified Log-Rank p = 0.57). For PFS2 we observed 99 and 100 events respectively in Arm A and B. Median PFS2 was equal to 5.0 months in Arm A and 5.8 months in Arm B (Stratified Log-Rank p = 0.68). Restraining PFS2 amongst patients receiving 2 lines (N = 124 pts), we observed 67 and 55 events respectively in Arm A and B, median PFS2 was equal to 6.3 months in Arm A and 8.8 months in Arm B (Stratified Log-Rank p = 0.03) Conclusions: Our results suggest that PFS2 for patients receiving 2 lines was longer when pts received Gemcitabine in 1st line. To be clinically meaningful definition of PFS1 and PFS2 should be optimized regarding censoring rules. New definitions should be proposed and assessed. No significant financial relationships to disclose.
Safety and tolerability of combined gemcitabine (G) and erlotinib (E) plus sorafenib (S) in the first-line treatment of metastatic pancreatic cancer
Authors: Cohen D. J. , Ryan T. , Moskovits T. , Cazeau N. , Newman E. , Pachter H. L. , Hochster H. S. 
Published: August 2020

e15594 Background: The addition of E to G results in improved survival for patients(pts) with locally advanced and metastatic pancreatic cancer. Many pancreatic tumors have constitutively activated ras/raf pathways and overexpress VEGF. Sorafenib, a multitargeted tyrosine kinase inhibitor which targets VEGR 1–3, PDGFR-α and β and the RAF/MEK/ERK pathway, when combined with G and E may synergize with these agents resulting in a more complete blockade of the signal transduction cascade in pancreatic cancer growth and progression and therefore improve outcome. Methods: Pts with previously untreated, histologically confirmed, unresectable pancreatic adenocarcinoma, ECOG PS 0–1, and adequate organ function were eligible and received G 1,000 mg/m2 over 30 min weekly × 3 every 4 weeks. E 150 mg PO daily and S 400 mg PO bid were given continuously. CT scans were performed every 2 cycles (8 weeks). Endpoints included safety and tolerability of the novel combination, PFS at 4 months, response rate, and OS. Results: Between 9/07–12/08 19 pts were enrolled with a median age 59 (range 45- 75), M/F 13/6, PS (0/1) 14/5. All 19 had metastatic disease. 17 pts are evaluable for toxicity and efficacy. The median number of cycles on treatment was 2 (range 1–10). The most common grade (gr) 3 toxicities were thrombocytopenia (24%), venous thrombosis (12%), and hyperbilirubinemia (12%). The most common gr 4 toxicity was infection (12%). 1 pt each experienced gr 3 HFSR, gr 3 diarrhea, gr 3 bleeding (epistaxis) and 1 had a non-fatal bowel perforation. There was 1 PR and 6 SD for an overall RR of 6% and a DCR of 41%. Conclusions: The combination of G and E plus S in the treatment of advanced pancreatic cancer is a well tolerated regimen without significant increased toxicity as compared to gemcitabine alone, except for very manageable cutaneous reactions. Further follow up is required to determine the combination's efficacy, though some patients have achieved prolonged disease stabilization. Supported in part by grants from Bayer Healthcare Pharmaceuticals/Onyx and OSI. [Table: see text]
Identification of chromosomal regions that harbor novel genes important for pancreatic cancer pathogenesis by genome-wide screening methods
Authors: Thieltges S. , Kalinina T. , Krohn A. , Simon R. , Moeller-Krull M. , Dierlamm J. , Izbicki J. , Yekebas E. 
Published: August 2020

e15609 Background: Pancreatic adenocarcinoma is a genetically highly complex and heterogenous tumor type with strong genetic instability which makes it resistant to therapy. Known amplifications of oncogenes such as KRAS or MYC and deletions of tumor suppresor genes such as CDKN2A and SMAD4 have demonstrated the importance of genetic alteration in this tumor type. Methods: We report the use of an Affymetrix Genome-Wide Human single nucleotide polymorphism (SNP) Array 6.0 (906,600 SNPs) to screen for gene copy number changes and allelic imbalances in 8 microdissected primary pancreatic tumors and 7 established pancreatic cancer cell lines. Gene Chip Human Genome U133 2.0 Array was used to make an RNA expression profile. Mutation analysis of KRAS and M-FISH analysis of cell lines was performed. Results: SNP arrays confirmed the presence of previously reported cytogenetic abnormalities in the cell lines and primary tumor probes, including MYC amplifikation at 8q24, gain of 17q12 (ERBB2/HER2), 7p12 (EGFR) and 12p12.1 (KRAS). KRAS mutation was seen in 71% of cell lines (5/7). We identified several alterations in signaling pathways such as Wnt/Notch Signaling and KRAS signaling. A sizeable subset ( 7 of 15 cases; 47%) showed an amplikon at 19q13.1–13.2 in which the serine/threonine kinase Mirk/Dyrk1B is localized, a downstream effector of oncogenic k-ras. There was also strong concordance between primary tumors and cell lines with respect to gains on 8q, 12p and 18q. Analysis of gene expression was used to localize potential target genes. M-FISH analysis showed complex karyotypes with chromosomal deletions in 9p and 18q, regions that are known to harbor tumor suppressor genes (CDKN2A, SMAD4 and TP53). Conclusions: Several signaling pathways mediate tumor cell survival. Analysis of gene amplification and RNA expression profile provide molecular biological characteristics and an individual gene signature of the tumor which allow us to choose more efficient drugs to an individualized treatment. Pathways activated by KRAS such as DYRK1B may offer new therapeutic targets. Further functional characterization is needed to provide evidence for the actual role of any putative target gene. No significant financial relationships to disclose.
Concomitant chemoradiation using gemcitabine in locally advanced hepatocellular carcinoma
Authors: Masood A. I. , Javed A. A. , Mateen A. , Gurchani S. A. 
Published: August 2020

e15611 Background: Hepatocellular carcinoma (HCC) is among the most common malignancies in Pakistan. There is currently no standard management for advanced HCC. Non-surgical modalities have demonstrated minimal improvements in survival. The aim of present study is to assess response rate and toxicity of concomitant gemcitabine and external radiation therapy (ERT) in locally advanced HCC. Methods: Thirty three biopsy proven advanced HCC patients having Okuda stage I and II disease were enrolled. 70 mg/m2 gemcitabine was given once weekly for three weeks during ERT. Partial liver ERT was delivered with 60Co upto 30 gray (Gy), 1.8 Gy/fraction and five fractions in a week. Tumor response was assessed by computed tomography (CT) eight weeks after completion of treatment. Response Evaluation Criteria in Solid Tumors (RECIST) was used to assess complete and partial response (CR, PR); progressive and stable disease (PD, SD). Hematological [neutropenia and thrombocytopenia], gastrointestinal (vomiting and diarrhea) and liver [encephalopathy, bilirubin, alanine and aspartate transferases (ALT and AST), and alkaline phosphatase (ALP)] toxicities were assessed weekly during treatment and then fortnightly upto 2 months according to Common Toxicity Criteria for Adverse Events version (3.0). Primary end point was to assess response rate at eight weeks after completion of treatment and Grade 3 or 4 toxicity during this period. Results: 28/33 patients were evaluable. No CR was seen. PR, SD and PD (%) were seen in 36, 39 and 25 of patients respectively. No grade 3 or 4 neutropenia was observed. 7/28 (25%) of patients developed grade 3 thrombocytopenia during treatment and needed a delay of one week for gemcitabine administration. Grade 3/4 toxicity (%) related to vomiting, diarrhea, encephalopathy, bilirubin, ALT, AST and ALP was seen in 18, 29, 21, 18, 14, 29 and 32 of the patients. Conclusions: The study showed that concomitant chemoradiation using 70mg/m2 gemcitabine is a feasible option with acceptable toxicity in locally advanced HCC. A larger study will be appropriate to define its definite role. No significant financial relationships to disclose.
Compare the diagnostic value of FLT and FDG PET/CT in assessment of regional lymph nodes in thoracic esophageal squamous cell carcinoma
Authors: Yu D. HanJ. , Zhong X. , Mu D. , Fu Z. , Zhang B. , Zhang L. , Zhang W. 
Published: August 2020

e15620 Background: To determine whether FLT PET/CT can detect regional lymph nodes metastases in untreated thoracic esophageal squamous cell carcinoma. In view of the reported high sensitivity of FDG PET/CT for the evaluation of thoracic nodules of esophageal carcinoma, we additionally performed FDG PET/CT for direct comparison with that of FLT. Methods: From March 2008 to December 2008, 18 patients with thoracic esophageal squamous cell carcinoma underwent dual-tracer PET/CT examinations before surgery. The results of reviewing side-by-side FDG PET/CT and FLT PET/CT images for the diagnosis of locoregional lymph node metastases were compared prospectively in relation to pathologic findings. The PET images were visually inspected with the maximum standardized uptake value (SUVmax) determined from a circular region of interest (ROI) over the entire lesion. The differential threshold for malignancy was set as SUVFDG≥2.5, and SUVFLT≥1.4, respectively. Results: All patients underwent esophagectomy and lymphadenectomy, and pathologic examination confirmed nodes positive for metastasis in 14 patients and 42 of 344 excised nodes. The uptake of FDG (median SUVmax, 5.59; range, 2.5–10.6) in locoregional lymph nodes metastasis was significantly higher than that of FLT (median SUVmax, 2.93; range, 1.6–4.6). There were 14 false positive nodes in FDG PET and only 3 in FLT PET, 7 false negative nodes in FDG PET, while 11 false negative nodes in FLT PET. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of FLT PET/CT were 73.81%, 99.01%, 95.93%, 91.18% and 96.45%, respectively, whereas those of FDG PET/CT were 83.33%, 95.36%, 93.90%, 71.43% and 95.36%, respectively. P values were 0.425, 0.014, 0.298, 0.055, and 0.541, respectively. Conclusions: FLT uptake in regional lymph node of esophageal carcinoma is significantly lower compared with FDG uptake.FLT PET has fewer false-positive findings compared with FDG PET. The specificity of FLT PET/CT is higher than that of FDG. We suggest that esophageal carcinoma N-staging need to combine FLT with FDG PET/CT images. No significant financial relationships to disclose.