bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between pancreatic tumor size as measured on 3D CT scan versus pathologic specimen: Impact on radiation treatment volume.
Authors: Qiu H. , Hsu C. C. , Fishman E. K. , Tuli R. , Wolfgang C. L. , Edil B. H. , Hruban R. H. , Zheng L. , Laheru D. , Herman J. M. 
Published: February 2017

276 Background: Definition of the target volume for irradiation of pancreatic cancer (PCA) must balance coverage of micrometastatic disease with toxicity. To determine differences between radiographically defined tumors and true pathologic tumor specimens, we correlated the maximum tumor diameter (TD) of preoperatively imaged tumors with resected tumor specimens. Methods: With IRB approval, a retrospective chart review of patients who underwent resection of PCA between 2006 and 2010 was conducted. 73 patients were identified with preoperative CT imaging and pathologic analysis of tumors. 70 of 73 patients had a preoperative 3D CT performed. The TD as measured by a radiologist (EF) on contrast CT and 3D CT reconstruction was compared with that measured by pathological analysis of the resected specimen. Results: 70 patients underwent resection with preoperative CT imaging; 14.1% of these patients had CT performed >6 weeks prior to surgery. The mean (SD) pathologic maximum TD was 31.3 mm (11.3) with range 3 mm to 60 mm. Whereas TD was underestimated by 1.9 mm (1.7 SE) with CT relative to pathologic analysis, this difference was not statistically significant (paired t-test, p=0.27) with a correlation coefficient of 0.265. 3D CT imaging had a smaller mean difference with a mean 3D CT diameter 0.4 mm (1.76 SE) larger than the pathologic specimen (p=0.82) with correlation coefficient 0.222. However, the max TD on 3D CT imaging was on average 2.3 mm larger than on CT (p=0.016) with correlation coefficient 0.798. Of patients with R0 resections (N=48), CT underestimated path size by 3.1 mm (p=0.020), whereas 3D CT was slightly larger (0.1 mm, p=0.949). For R1 resections (n=22), both CT and 3D CT overestimated size (0.8 mm and 1.1 mm, respectively, p>0.5). Conclusions: PCA TD is generally underestimated on CT imaging, yet better approximated with 3D CT. Improved correlation was seen between CT and pathologic specimens following R0 resection. Alternatively, R1 resection specimens were slightly overestimated by CT/3D CT imaging. As a result, clinical target volumes should be expanded accordingly during radiotherapy planning to properly account for these discrepancies in the gross tumor. No significant financial relationships to disclose.
Long-term results of full-dose gemcitabine with radiation therapy compared to 5-fluorouracil with radiation therapy for locally advanced pancreatic cancer.
Authors: Huang J. , Robertson J. M. , Margolis J. H. , Balaraman S. , Gustafson G. S. , Khilanani P. V. , Nadeau L. , Jury R. P. , McIntosh B. 
Published: February 2017

287 Background: To retrospectively compare the efficacy and toxicity of full-dose gemcitabine-based chemoradiotherapy (GemRT) vs. 5-fluorouracil (5-FU)-based chemoradiotherapy (5FURT) for locally advanced pancreas cancer (LAPC). Methods: From January 1998 to December 2008, 93 patients with LAPC were treated either with 5FURT (n=38) or GemRT (n=55). 5FURT consisted of standard-field radiotherapy given concurrently with infusional 5-FU or capecitabine. GemRT consisted of involved-field radiotherapy given concurrently with full-dose gemcitabine (1000 mg/m2 weekly) with or without erlotinib. The follow-up time was calculated from the time of diagnosis to the date of death or last contact. Results: Eighty-eight of 93 patients have died, and only one was lost to follow-up after developing DM. The median OS was 11.2 months (range 1.5-96). Patient characteristics (including Zubrod score, age, tumor stage, nodal stage, tumor location, and grade) were not significantly different between treatment groups. The OS was significantly better for GemRT compared to 5FURT (median 12.5 months vs. 10.2 months; 51% vs. 34% at 1 year; 12% vs. 0% at 3 years; 7% vs. 0% at 5 years; respectively; p=0.04), although the two groups had same DM (34% at 1 year). GemRT cohort was more likely to receive gemcitabine before or after chemoradiotherapy than 5FURT cohort (85% vs. 37%, p<0.001). Of the subset who received gemcitabine either before or after chemoradiotherapy, OS was still significantly better for GemRT without concurrent erlotinib compared to 5FURT (median 15.1 months vs. 10.7 months; 70% vs. 36% at 1 year; 21% vs. 0% at 3 years; 11% vs. 0% at 5 years; respectively; p=0.005), as was the rate of DM (23% vs. 45%; respectively; p=0.04). The subsequent hospitalization, percent of survival time spend in the hospital, acute and late grade 3-5 gastrointestinal toxicities were not significantly different between the GemRT and 5FURT groups. Conclusions: Full-dose GemRT was associated with improved OS compared to standard 5FURT. This approach yielded a moderate number of long-term survivors and was not associated with increased hospitalization or severe gastrointestinal toxicity. No significant financial relationships to disclose.
Resection of liver metastases from breast cancer: Effect of timing of surgery and estrogen receptor status on outcome.
Authors: Abbott D. E. , Brouquet A. , Meric-Bernstam F. , Valero V. , Green M. C. , Kuerer H. M. , Curley S. A. , Abdalla E. K. , Hunt K. , Vauthey J. 
Published: February 2017

288 Background: The oncologic benefit of resecting liver metastases (LM) in breast cancer patients is unclear. Identifying predictors of improved outcome would be useful in selecting appropriate candidates for surgery. Methods: From 1997 to 2010, 86 breast cancer patients underwent LM resection. RECIST criteria were used to define the best response to chemotherapy as the optimal response at any time during the course of metastatic disease and the preoperative response to chemotherapy as the response immediately before LM resection. Univariate and multivariate analyses were used to identify predictors of survival. Results: Sixty-four patients (74%) had primary tumors that were either estrogen receptor (ER) or progesterone receptor (PR) positive. Fifty-three patients (62%) had solitary LM, and 73 patients (85%) had LM smaller than 5 cm. Sixty-five patients (76%) received preoperative chemotherapy, and 10 patients (12%) received 2 or more chemotherapy regimens before LM resection. Only 2 patients (3%) had progressive disease (PD) as a best response to chemotherapy, whereas 19 patients (29%) had PD as preoperative response to chemotherapy (p < 0.001). No perioperative mortality was observed. At a median follow-up of 62 months, the median durations of overall and disease-free survival were 57 and 14 months. Univariate analysis revealed that ER and PR primary tumor status, best response to chemotherapy, and preoperative response to chemotherapy were associated with overall survival after LM resection. On multivariate analysis, an ER-negative primary tumor (p=.009, hazard ratio [HR] = 3.3, 95% confidence interval [CI] =1.4-8.2) and preoperative disease progression (p=.003, HR = 3.8, 95% CI = 1.6-9.2) were independently associated with worse survival after LM resection. Conclusions: Resection of liver metastases in breast cancer patients with ER positive disease that is responsive to chemotherapy is associated with prolonged survival. Timing of surgery is critical and resection before progression is associated with better outcome. No significant financial relationships to disclose.
Extrapulmonary neuroendocrine tumors: An institutional experience of 337 patients at the National Cancer Center Hospital in Japan.
Authors: Terashima T. , Morizane C. , Ueno H. , Ikeda M. , Saito Y. , Shimada Y. , Kushima R. , Hiraoka N. , Kanai Y. , Okusaka T. 
Published: February 2017

293 Background: Extrapulmonary neuroendocrine tumors (EPNET) are a rare and heterogeneous disease entity, and little information regarding these tumors is available. The aim of the present study was to clarify the clinical behavior, treatment strategy, and outcome of EPNET arising from various primary sites. Methods: We retrospectively reviewed the medical records of 337 patients with pathologically confirmed NET arising from extrapulmonary site between January 2000 and December 2008 at the National Cancer Center Hospital of Japan. Results: The major primary tumor site was the rectum followed by the pancreas and stomach. Among the gastrointestinal tract tumors, 113 patients had NET from the foregut, 92 patients from the hindgut, and only 4 patients from the midgut. The median patient age was 60 years, and 57% of the patients were male. The histologic grade was as follows: 39% were well-differentiated neuroendocrine tumors (WDNET); 20% were well-differentiated neuroendcrine carcinomas (WDNEC); 33% were poorly differentiated neuroendocrine carcinomas (PDNEC); and 8% were mixed exocrine-endocrine tumors (Mixed). Most NETs from the rectum or duodenum are WDNET, whereas the ratio of PDNEC was high among NET from the genital organs or esophagus. The treatment strategy was associated with the clinical stage or the primary organ; in particular, 94% of the localized rectal NET were resected endoscopically. The 2-year survival rate for all the patients were 70%. A multivariate analysis demonstrated that distant disease of clinical stage and PDNEC of histological grade had a stronger impact on a poor outcome than the primary tumor site. The 2-year survival rate among the patients with WDNET, WDNEC and PDNEC were 97%, 80% and 36%, respectively, and 94%, 72%, and 32% of the patients had localized, regional, and distant disease, respectively. Conclusions: Japanese patients with EPNET have different clinicopathological features such as the primary organ or treatment procedure compared with previous reports in Western countries. Identifying the precise clinical stage and histological grade of patients with NET is essential because these factors influence the patient outcome. No significant financial relationships to disclose.
Ethanol-induced DNA damage and the expression of repair-related molecules in human gastric carcinoma AGS cells with use of an acid pump antagonist and proton pump inhibitor.
Authors: Cho H. , Chun H. , Keum B. , Kim Y. , Jeen Y. , Seo Y. , Lee H. , Um S. , Kim C. , Ryu H. 
Published: February 2017

30 Background: Proton pump inhibitor (PPI) inhibits gastric acid secretion by strongly suppressing H + / K +- ATPase of parietal cells and is a major drug for peptic ulcers and gastroesophageal reflux. Recently it was reported that PPI has antioxidant and anti- inflammatory effects as well as a powerful acid inhibitory effect. To analyze the DNA repair capacity from the antioxidant effect of acid pump antagonist (Revanex-RN) and proton pump inhibitor (Omeprazole-OP), this study examined ethanol-induced DNA damage and the expression of repair related molecules in human gastric cancer AGS cells pretreated with an acid pump antagonist and a proton pump inhibitor. Methods: AGS, a human gastric cancer cell line was obtained from ATCC, was treated with ethanol (0, 2, 4, 6, 8, 10%) during 1hr. MTT and Comet assay were performed to evaluate ethanol-induced DNA damage. The optimum concentration of ethanol which caused DNA damage was established. And AGS cells were cultured in proper concentration of RN or OP overnight. Then, these cells were treated with 5% ethanol during 1hr. DNA damage and recovery were represented the value of Olive tail moment in comet assay. Western blot was also performed to detect expression of DNA polymerase beta, APE/ref-1, PCNA, and GADD45. Results: The DNA damage of AGS cell depended upon ethanol concentration distinctly. Damaged cells showed up recovered tendency in the group treated with low dose RN or OP. In addition, DNA repair enzymes including DNA polymerase beta and APE/ref-1 which were associated with mechanism of base excision repair (BER) were increased. A relevant protein such as GADD45 was also increased significantly. Conclusions: PPI has capacity to recover damaged DNA, which is associated with increased expression of GADD45 directly. Therefore, PPI offers cancer prevention by reducing the level of DNA damage in the gastric mucosa. GADD45 is also likely to suggest that it could be used a major factor on the injury mechanism and an indicator of mucosal damage in stomach. Moreover, RN, an acid pump antagonist is expected to have the higher safety compared to the existing PPIs and considered to be equal to PPIs in terms of anti-cancer effect. No significant financial relationships to disclose.
Radioembolization of unresectable primary and secondary hepatic malignancies using yttrium-90: The University of Texas at Houston experience.
Authors: Subbiah I. M. , Cen P. , Tanikella R. , Bryant K. W. , Liaw V. J. , Fallon M. B. , Cohen A. M. 
Published: February 2017

311 Background: Few effective treatments exist for unresectable hepatic malignant lesions. The objective of this study was to analyze the patient outcomes and toxicities of yttrium-90 (Y90) radioembolization in patients with unresectable primary and secondary hepatic malignancies. Methods: A retrospective review from 3/03 to11/09 of pts with liver malignancies who received Y-90 (TheraSphere and SIR-Spheres) was conducted. Pretreatment CT scans characterized the liver lesions. Hepatic arterial Tc-99m MAA scans showed % lung shunt and liver flow. Postprocedure toxicities (including pt symptoms, lab values) were recorded. CT/MRI scans at 1-, 3-, and 6-month intervals measured tumor response as per RECIST 1.0. The Kaplan-Meier method was used for survival analyses. Results: 50 pts were initially screened, of which 44 pts received 63 Y90 treatments. Mean age was 62y (24 male, 20 female). Of the 44 pts, 15 had hepatocellular cancer (HCC), 2 had intrahepatic cholangiocarcinoma and 27 had liver metastases (10 colorectal, 8 breast, 4 carcinoid, 1 esophagus, 1 lung, 1 gallbladder, 1 pancreas, 1 gastric). Mean tumor size was 10.6 cm (range 2.2-23.5cm), mean tumor absorbed dose was 30.8 mCi (range 7.1-63.5 mCi). Post-procedure symptoms included fatigue (n=21, 47.7%), abdominal pain (n=35, 79.5%), nausea/vomiting (n=12, 27.2%). At 1 month, 20 pts (45.5%) had SD, 14 (31.8%) had PR, and 10 (22.7%) had PD. At 3 months, 25 patients had SD, 10 had PD and 9 pts were in hospice or were deceased. At 6 months, 11 pts had SD. Per RECIST, PD at 1, 3, 6- months were significant predictors of mortality (OR 25, p<0.0002) as was the preprocedure MELD (OR 1.208, p=0.0160). Caucasian pts had a lower overall mortality (OR 1.238, p=0.0363). Survival analyses will be updated. One pt with HCC was successfully downstaged after Y90 and listed for liver transplant; 26 patients were alive at 6-month follow-up. Conclusions: Y90 radioembolization represents a pragmatic option for hepatic lesions malignancies not amenable to resection. With an acceptable safety profile and the promising response on imaging, Y90 warrants further trials into its ideal use in the therapeutic algorithm for unresectable liver lesions. No significant financial relationships to disclose.
Phase I study of AMG 479, a fully human monoclonal antibody against the type 1 insulin-like growth factor receptor (IGF-1R), in Japanese patients (pts) with advanced solid tumors.
Authors: Doi T. , Fuse N. , Yoshino T. , Murakami H. , Yamamoto N. , Boku N. , Otani S. , Shibayama K. , Takubo T. , Elwyn L. 
Published: February 2017

318 Background: AMG 479 is a fully human monoclonal antibody against human IGF-1R that inhibits the survival and proliferative signals driven by IGF-1 and -2. Methods: Patients (Pts) were enrolled into 1 of 3 dose cohorts (6, 12 or 20 mg/kg) of single-agent AMG 479 administered intravenously Q2W. Dose-limiting toxicity (DLT) was assessed for the first 28 days. The primary objectives were to assess the safety, tolerability, and pharmacokinetics (PK) of AMG 479 in Japanese pts with advanced solid tumors. An exploratory pharmacodynamic (PD) analysis was done to investigate the relationship between exposure and changes in the level of circulating factors in IGF-1R pathway (IGFBP-3 and total IGF-1). Results: Nineteen pts with ECOG 0-1 (6 in cohort 1 and 3, 7 in cohort 2) received at least 1 dose of AMG 479. Median age was 58.0 years. Tumor types included: breast (4), gastric (3), rectal (2), NSCL (2), thymic (2), and other cancers (6). Enrollment has been completed; 5 pts remained on study as of 15 March 2010. No DLTs were observed. Three serious adverse events (SAE) were reported, only respiratory tract haemorrhage in a subject with thymic carcinoma was considered by the investigator to be related to AMG 479. The most common grade ≥3 AEs were neutropenia (21%), leukopenia (16%) and lymphopenia (11%). There was a trend of dose-dependency on severity of thrombocytopenia, but not on that of neutropenia. No neutralizing anti-AMG 479 antibodies were detected. PK was dose-linear and similar to PK in non-Japanese pts. Tumor response data were available for 17 pts. Stable disease (defined as a lack of progression at the first 8-week assessment) as best response was reported in 6 pts and progressive disease was reported in 11 pts. Exploratory PD marker analysis demonstrating exposure dependent changes will be presented. Conclusions: AMG 479 up to 20 mg/kg was tolerable in Japanese pts with advanced solid tumors. The AE and PK profiles were similar to those previously observed in non-Japanese pts. An international phase 3 study in metastatic pancreatic cancer pts is planned based on the promising results from phase 1b/2 study (ASCO 2010, Abs 4035). [Table: see text]
Pilot study of neoadjuvant FOLFIRINOX in unresectable locally advanced (LA) pancreatic carcinoma (PC).
Authors: Hosein P. J. , Kawamura C. , Macintyre J. , Loaiza-Bonilla A. , Merchan J. R. , Levi J. U. , Rocha Lima C. S. 
Published: February 2017

324 Background: 5-flourouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) is superior to gemcitabine in patients (pts) with advanced PC who have a good performance status (Conroy et al, ACCORD 11 trial, ASCO 2010). After the initial data on FOLFIRINOX were presented at ASCO 2007, we began using it off-protocol as neoadjuvant therapy for LAPC. We report our experience herein. Methods: In this retrospective series, we included pts with unresectable LAPC who received neoadjuvant FOLFIRINOX. The doses were identical to the ACCORD 11 trial, with G-CSF prophylaxis from cycle 1. The primary endpoint was R0 resection rate. Secondary endpoints were overall survival (OS), safety and tolerability. Results: Between 5/2008 and 9/2010, we treated 12 pts with LAPC with neoadjuvant FOLFIRINOX. All pts met consensus criteria for unresectability after multidisciplinary review. The median age was 57.5 years and 9/12 were men. All had ECOG PS of 0 or 1. Two pts received gemcitabine prior to FOLFIRINOX and 10 were treatment-naive. Two pts are still on therapy and 10 completed a median of 6 cycles (range 3-17) and were evaluable; 6 were felt to have converted to resectability by imaging and were taken for surgery. Four had R0 resections (40% of evaluable, 33% of all patients), 1 had R1 resection, and 1 had unresectable disease at laparotomy. To date, 2 pts have died and 10 remain alive with a Kaplan-Meier estimated median OS of 20.7 months (95% CI 18.8-22.6). All 4 pts with R0 resections are alive and disease- free. Grade 3/4 chemotherapy-related toxicities were neutropenia (17%), neutropenic fever (8%) and fatigue (17%). Common grade 1/2 toxicities were neutropenia (42%), anemia (92%), thrombocytopenia (50%), fatigue (92%), nausea (58%), diarrhea (42%) and neuropathy (33%). Two of the 6 surgical pts had significant postoperative complications - 1 with C. Difficile colitis, gastroparesis and a subhepatic collection and another with an infected pancreatic bed collection requiring percutaneous drainage 3 times. Conclusions: FOLFIRINOX is feasible as neoadjuvant therapy in patients with unresectable LAPC, with manageable toxicities. In this small series, the R0 resection rate was at least 33%. A prospective trial is warranted. No significant financial relationships to disclose.
The feasibility, safety, and technique of endoscopic ultrasound (EUS)-guided fiducial marker placement for stereotactic body radiation therapy (SBRT) in borderline resectable pancreatic cancer.
Authors: Vignesh S. , Hoffe S. E. , Shridhar R. , Klapman J. , Barthel J. S. 
Published: February 2017

327 Background: Fiducial markers implanted into tumors that move with respiration facilitate planning for SBRT. To date, there is little evidence regarding the safety and utility of EUS implanted markers for “borderline resectable” pancreatic cancer. Methods: This is a retrospective review of 13 patients (7 men and 6 women) with “borderline resectable” pancreatic cancer as per NCCN guidelines. EUS-guided fiducial placement for stereotactic body radiation therapy was performed between January 2009 and September 2010. Gold cylindrical fiducials (0.35mmx 10mm or 0.75 mm X 10 mm; VISICOIL) were loaded into a 22g or 19 g EUS needle. With the needle in the target, the fiducial was deployed by retracting the needle and advancing the stylet. EUS confirmed fiducial position after deployment. A mean of 3 fiducials were placed (range 1-6) per patient. Fiducial position was analyzed at 4D CT simulation and daily cone beam imaging prior to SBRT. Results: Fiducial placement was successful in all. Technical difficulty was encountered in 2 patients secondary to retained food in stomach and uncinate tumors. Smaller (10x0.35mm) fiducials were successfully placed in these 2 patients. 3 patients had abdominal pain lasting < 12 hours after fiducial placement but none had any acute complications. In 2 patients, change in fiducial position was noted on follow-up cone beam CT. This apparent change in position was related to biliary drainage, gastric distension and a pre-existing pseudocyst. Though this is not indicative of fiducial migration, it impacts radiation planning and delivery. No complications were noted at the end of a mean follow-up period of 6 months. Conclusions: EUS fiducial placement to assist with stereotactic body radiation for “borderline resectable” pancreatic cancer is safe, feasible, and technically successful in most cases. True migration did not occur but other factors may cause an apparent change in fiducial position. Further studies are planned to optimize the best configuration of fiducial placement by virtue of tumor location for SBRT planning and treatment. No significant financial relationships to disclose.