bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors associated with surgical resection for pancreatic and periampullary carcinomas in a cancer center in Mexico City.
Authors: Onate-Ocana Luis F. , Bermudez-Benitez Elyzabeth , Ortiz-Toledo Miguel Angel , Ochoa-Carrillo Francisco J. , Aiello-Crocifoglio Vincenzo 
Published: February 2017

191 Background: Medical information regarding periampullary neoplasms is scarce in Mexico. Therefore, our aim is to report our experience with pancreatic and periampullary neoplasms, with attention to factors associated to surgical resection in a Cancer Center. Methods: A retrospective analysis of medical records of all patients with malignant neoplasms located at periampullary region demonstrated by biopsy from January 2005 to December 2010. Factors associated to resectability or survival were calculated employing logistic regression or Cox models. Results: A total of 464 patients with neoplasms of the periampullary region were identified, 249 women and 215 males (mean age 60.2 years). Pancreatic cancer was reported in 269 cases (58%), ampullary in 91 (19.6%), duodenal in 63 (13.6%), intrapancreatic bile duct in 15 (3.2%), neuroendocrine neoplasms in 13 (2.8%) and other types in 13 (2.8%). Sixty-two pancreatoduodenectomies were performed in this 6-year period (13.4% resectability). Sixty-one patients were stages I or II, and 403 stages III or IV. Age (odds ratio [OR] 0.97; 95% confidence interval [CI] 0.96-0.99) and ampullary carcinoma (OR 6.09; 95% CI 3.4-10.8) were the only factors associated to resectability (p<0.0001). Median overall survival of the cohort was 2.9 months (95% CI 2.4-3.4). Factors associated to overall survival with their estimators of the Cox model (p<0.00001) are shown in the Table. Conclusions: Resectability is low and advanced stages are frequent. Young age and location in the ampulla defines increased probability of resection. Overall survival is associated to younger age, being female, ampullary carcinoma, neuroendocrine carcinoma and surgical resection. [Table: see text]
Activity of cabozantinib (XL184) in hepatocellular carcinoma patients (pts): Results from a phase II randomized discontinuation trial (RDT).
Authors: Cohn Allen Lee , Kelley Robin Katie , Yang Tsai-Shen , Su Wu-Chou , Verslype Chris , Ramies David A. , Lee Yihua , Shen Xiaodong , Van Cutsem Eric 
Published: February 2017

261 Background: Cabozantinib is an oral, potent inhibitor of MET and VEGFR2. MET over-expression has been observed in advanced hepatocellular carcinoma (HCC). Anti-VEGF pathway agents have shown clinical benefit in pts w/ HCC. Simultaneous targeting of the MET and VEGF signaling pathways with cabozantinib may therefore be a promising treatment strategy. Methods: HCC pts with progressive measurable disease, per mRECIST received cabozantinib at 100 mg qd PO over a 12 week Lead-in period. Up to one prior regimen was allowed and only pts with Child-Pugh score of A were eligible. Tumor response was assessed every 6 weeks. Treatment beyond Week 12 was based on response: pts with PR continued open-label cabozantinib, those with SD were randomized to cabozantinib vs. placebo, and those with PD discontinued study drug. The primary endpoint was overall response rate (RR) per mRECIST in the Lead-in period, and progression free survival for pts who entered the randomized period. Results: Enrollment has been completed with 41 pts. Results are available for 34 pts. Median age: 61 years (33 to 83). Males: 24/34 (71%). Asian: 13/34 (38%). HCC etiology: Hepatitis B or C 12/34 (35%); alcohol abuse 5/34 (15%); other 17/34 (50%). Extrahepatic spread was observed in 21/34 (62%). The median number of prior systemic treatments was 1; prior sorafenib: 16/34 (47%). Most common related AEs ≥Grade 3 were hand-foot syndrome (15%), diarrhea (9%) and thrombocytopenia (9%). 3/33 pts evaluable for tumor assessment at 12 weeks achieved PR by original RECIST (RR 9%). One additional pt randomized at Week 12 achieved PR at 18 weeks and treatment remains blinded on study for >1 year. 24/30 pts (80%) with ≥1 post-baseline scan had tumor regression (with no apparent relationship to prior sorafenib therapy). The overall disease control rate (DCR = PR+SD) at Week 12: 71% (Asian subgroup: 77%). Median time on study: 6 mos (1 to 15+ mos). AFP responses (defined as reduction from baseline of >50%) in 21 pts with ≥1 post-baseline result: 9/21 (43%). Conclusions: Cabozantinib exhibits clinical activity in HCC pts with advanced disease, regardless of prior sorafenib treatment as reflected by tumor reduction, high DCR and time on study.
Multimodality therapy for borderline resectable pancreatic cancer: A single-institution experience.
Authors: Pimiento Jose Mario , Hutchinson Tai , Weber Jill M. , Patel Manish R. , Hodul Pamela Joy , Chuong Michael D. , Springett Gregory M. , Hoffe Sarah E. , Karl Richard C. , Centeno Barbara , Klapman Jason , Shridhar Ravi , Chen Dung-Tsa , Malafa Mokenge Peter 
Published: February 2017

280 Background: Multimodality therapy has been advocated for borderline resectable pancreatic cancer (BRCP); however, specific regimens vary widely by institution. Outcomes of these interventions need to be examined to inform future investigation of the optimal therapy for these patients. This study represents the experience of multimodality therapy for BRPC at an NCI designated cancer center. Methods: We identified all patients (pts) with operable pancreatic ductal adenocarcinoma (PDA) from 2006 to 2011. Patients were divided into two groups: resectable group and BRPC group as per the NCCN and AHPBA consensus guidelines. Primary outcomes were resection rate, microscopic negative margin (R0) resection rate, overall survival (OS), and disease free survival (DFS). Fisher's exact and chi-square were used for group comparison while Kaplan-Meier estimates was used for survival analysis. Results: 160pts were identified with operable PDA. 100 (63%) pts had resectable tumors, and 60 (37%) pts had borderline resectable tumors. Neoadjuvant therapy (NT) was administered to 0% in the group with resectable tumors, and 100% in the group with borderline resectable tumors. The resection rate was 100% in pts with resectable tumors and 58% in pts with borderline resectable tumors. R0 resection rates were 80% in the resectable tumors and 97% in the borderline resectable tumors following NT. Perioperative mortality was <1% (1/125) for resectable tumors and 0% in borderline resectable tumors. Median OS was 22.6 months (m) for pts that had resectable tumors and 13.9m for all pts with borderline resectable tumors (p=0.017); however, the median OS for resected pts with borderline resectable tumors was 21.5m (p=0.6). Improved DFS was seen in patients with resectable tumors when compared with resected borderline resectable tumors (15 vs. 9.5m; p=0.04). Conclusions: Multimodality therapy leads to high rates of R0 resections in borderline resectable pancreatic cancer; however 42% of patients progressed during NT. The overall survival for patients with resected borderline resectable pancreatic cancer following NT is similar to patients who undergo resection for resectable pancreatic cancer.
Initial experience using percutaneous irreversible electroporation (IRE) in the treatment of locally advanced pancreatic adenocarcinoma (LAPC) with vascular encasement.
Authors: Hosein Peter Joel , Barbery Katuska J , Perez-Rojas Evelyn , Froud Tatiana , Rocha Lima Caio Max S. , Franceschi Dido , Livingstone Alan S , Yrizarry Jose M , Narayanan Govindarajan 
Published: February 2017

291 Background: Neoadjuvant chemoradiation therapy can convert some patients (pts) with borderline or unresectable LAPC to resectability. Persistent vascular encasement after neoadjuvant therapy usually contraindicates resection. IRE using the Nanoknife is more versatile than other ablative modalities in that tumors abutting vascular structures can be treated with IRE without compromise of the vessels or concern for the heat sink effect of nearby blood flow. Methods: We examined the records of pts referred for IRE for LAPC. The procedures were all done percutaneously under general anesthesia using a standard protocol. The primary endpoint was safety. Secondary endpoints included survival and resection rate after the procedure. Results: Between 12/2010 and 8/2011, 8 pts with biopsy-proven PC underwent percutaneous ablation of pancreatic tumors using IRE. The median age was 53 years (range 51-72), the median time from diagnosis to IRE was 8.8 months (range 2.4-29.2) and the median tumor size treated was 2.8cm (range 2.5-6.8). All pts had prior chemotherapy and 7 had prior radiation, with a median of 2 lines of prior therapies (range 1-4). Two pts went to surgery after IRE after 4 and 5 months respectively. Both had margin-negative (R0) resections and one had a pathologic complete response. Both remain disease-free at 1 and 5 months after resection respectively. Among the 6 remaining pts, 2 were lost to follow-up, one had progressive disease after 3 months and 3 remain under follow-up to determine resectability. One of these 3 pts had a negative follow-up PET scan and surgery is planned. The procedure was complicated by a spontaneous pneumothorax during anesthesia in one patient, and another developed pancreatitis; both recovered completely. Conclusions: Percutaneous ablation of pancreatic tumors appears to be feasible and safe using the IRE modality. In our initial experience, 2 out of 8 pts with unresectable LAPC due to persistent vascular encasement after neoadjuvant therapy achieved a margin-negative resection after IRE. One had a pathological complete response. A prospective neoadjuvant trial in LAPC incorporating IRE is planned.
A phase I open-label, dose-escalation study of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer.
Authors: Littman Susan Joy , Monti Daniel , Newberg Andrew , Bazzan Anthony , Pillai Madhavan V. , Lewis Nancy , Yeo Charles , Levine Mark , Mitchell Edith P. 
Published: February 2017

323 Background: IV ascorbic acid (vit c) is a prodrug for steady state formation of ascorbate radical (Asc·-) in the extracellular space resulting in sustained production of H2O2 leading to selective killing of tumor cells by a pro-oxidative mechanism. In preclinical models of panc cancer pharmacologic concentrations of Asc·- with gem resulted in a synergistic cytotoxic response. We conducted a Phase I dose escalation study of IV ascorbic acid with gem plus erlotinib chemo as first line therapy in panc cancer. Methods: Patients with adv panc cancer were enrolled using a standard 3+3+3 design to assess the safety and pharmacology of IV vit c in combo with gem and erlotinib. Cohort 1 received 50 g IV vit c and subsequent cohorts were escalated by 25 g to a final dose of 100 g. Pts were given 3 infusions of vit c per week on separate days for 8 w (1 cycle). IV gem was given on day 1 (1000 mg/m2) and weekly for 7 w followed by a rest week. Oral erlotinib (100 mg) was given daily for 8 w. Trt continued until disease progression or toxicity. Steady state ascorbate PK was assessed in cohorts 2 and 3. AEs were determined using NCI CTCAE v3.0. Tumor responses were assessed per RECIST. Results: Of 14 pts enrolled, 9 or 3 per cohort completed the study. Median age was 64 years. 5 pts did not complete trt (2 discontinued, 3 died). 9 pts completed at least 24 ascorbic acid trts and 1 cycle of gem/erlotinib therapy. There were 24 AEs. These included 15 non-serious AEs and 8 SAEs. The most frequent AEs were grade 1/2 thrombocytopenia. Other grade 1/2 events included anemia, hyperglycemia, abd discomfort, ascites and infection. SAEs: 2 grade 3 heme, 1 grade 3 GI, 1 grade 3 infectious and 2 grade 4 thrombosis. Plasma asc levels were 25.3 - 31.9 mm/L for pts receiving the 100g dose. 8 of the 9 pts had a reduction in the panc primary with 1 pt having no change at 8 w. For non-target lesions, 2 had PD and 7 had SD per RECIST. Conclusions: Overall safety data do not reveal AEs other than those expected in patients with metastatic panc cancer and/or treatment with gem and erlotinib. Addition of IV ascorbic acid did not increase toxicity. Preliminary efficacy results are encouraging. A phase II study is planned.
Washington University experience with FOLFIRINOX in pancreatic cancer.
Authors: Peddi Parvin F. , Tan Benjamin R. , Picus Joel , Sorscher Steven , Suresh Rama , Lockhart Albert C. , Menias Christine , Linehan David , Wang-Gillam Andrea 
Published: February 2017

354 Background: The FOLFIRINOX (5-FU, leucovorin, irinotecan, oxaliplatin) regimen has recently been shown to be an effective treatment with a significant survival benefit in patients with metastatic pancreatic cancer. Concern for treatment-related toxicity, however, has hampered the adoption of this regimen in clinical practice. A FOLFIRINOX registry was created at our institution to document FOLFIRINOX tolerability and efficacy. Methods: Patients with pancreatic cancer who had received at least one dose of FOLFIRINOX were enrolled in the registry. Demographic information, treatment dosage, adverse events, and efficacy data were obtained. Radiographic response was independently verified by a radiologist. Results: Between January 2010 and August 2011, 29 patients were identified with a median age of 57 (range 37-71). 26 (92.8%) had ECOG performance status of 0-1. FOFIRINOX was given to 16 patients with metastatic disease, 12 with locally advanced disease, and one with borderline resectable disease. 17 (61%) received the first cycle with a dose reduction in either irinotecan and/or 5-FU dosage. UGT1A1*28/*28 homozygous genotype was found in 4 patients who all received dose reduced irinotecan. 13 patients (46%) were started on G-CSF prophylactically with the first cycle while 5 additional patients (18%) had G-CSF support added in later cycles. Main adverse events were neutropenia (grade 3-4 in 14.2%), and abdominal pain and diarrhea (grade 3-4 in 7% and 4% respectively). One incidence of neutropenic fever was observed. Four patients were hospitalized for treatment-related toxicity while three had therapy discontinued due to intolerance. At present, 19 patients have imaging available to determine efficacy: 5 (26%) had partial response, 12 (63%) stable disease, and 2 (11%) had progression of disease as their best response. For patients with locally advanced disease, 11 out of 12 had clinical benefit on FOLFIRINOX. Conclusions: In our practice, FOLFIRINOX was well tolerated and was efficacious, consistent with previously published data. It was frequently used in the setting of locally advanced disease and had similar benefit and tolerability in this setting.
Phase II study of sunitinib (SU) in Japanese patients with unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumor (NET).
Authors: Okusaka Takuji , Ito Tetsuhide , Nishida Toshirou , Igarashi Hisato , Mizuno Nobumasa , Hara Kazuo , Morizane Chigusa , Kondo Shunsuke , Hashigaki Satoshi , Kimura Nobuyuki , Okano Kyoko , Tanuma Junichi , Murakami Mami , Sawaki Akira , Yamao Kenji , Imamura Masayuki 
Published: February 2017

381 Background: SU is an oral, multitargeted, antiangiogenic, tyrosine kinase inhibitor effective in patients (pts) with unresectable, well-differentiated pancreatic NET. This open-label, phase II study examined whether SU is also effective in Japanese pts with this disease. Methods: Japanese pts received SU 37.5 mg/day on a continuous daily dosing (CDD) schedule (28-day cycle). The primary endpoint was clinical benefit rate (CBR; complete response [CR] + partial response [PR] + stable disease [SD] ≥24 weeks). Secondary endpoints included: objective response rate (ORR; CR + PR), 6-mos progression-free survival (PFS) probability, safety and pharmacokinetics. Tumor assessments were performed at baseline and 8-wk intervals by CT or MRI (RECIST). Results: Twelve patients were enrolled and received treatment (tx; median age 54 yrs, range 34–79); 9 were ongoing at data cut-off (July 1, 2011). CBR was 75.0% (95% CI 42.8, 94.5), comprising 5 PRs and 4 pts with SD ≥24 weeks. ORR was 41.7% (95% CI 15.2, 72.3). 6-mos PFS probability was 91.7% (95% CI 53.9, 98.8). One PR occurred in a pt with gastrinoma, in whom gastrin levels decreased by 93% and tumor bulk decreased by 45%. All-causality, any-grade (G) AEs included diarrhea (n=9, 75%), HFS and hypertension (both n=8, 67%). Neutropenia was the most common G3 AE (n=5, 42%, all tx-related). Three pts (25%) experienced G4 AEs (herpes encephalitis, convulsion, loss of consciousness [n=1] and lipase increased [n=2], all tx-related).Two pts (17%) experienced serious AEs: convulsion and loss of consciousness (n=1, tx-related), and acute cholecystitis (n=1, unrelated to tx). There were no deaths on study; one death due to disease progression occurred 3 mos after study withdrawal. On day 15 (cycle 1), mean trough plasma concentrations (n=10) for SU, its metabolite, and SU + metabolite were 53.9, 23.7 and 77.5 ng/mL, respectively. SU on a CDD schedule resulted in sustained drug concentrations without accumulation across cycles. Conclusions: SU 37.5 mg/day on a CDD schedule demonstrated antitumor activity in Japanese pts with unresectable, well-differentiated pancreatic NET. Common AEs were consistent with the known safety profile of SU.
Final results from study 181: Randomized phase III study of FOLFIRI with or without panitumumab (pmab) for the treatment of second-line metastatic colorectal cancer (mCRC).
Authors: Sobrero Alberto F. , Peeters Marc , Price Timothy Jay , Hotko Yevhen , Cervantes-Ruiperez Andres , Ducreux Michel , Andre Thierry , Chan Emily , Lordick Florian , Tian Ying , Sidhu Roger 
Published: February 2017

387 Background: In the primary analysis of study 181, pmab+FOLFIRI significantly improved progression-free survival (PFS) vs FOLFIRI as second-line therapy in patients (pts) with wild-type (WT) KRAS mCRC. Here, we report the results of a prespecified final descriptive analysis planned for 30 months (mos) after the last pt was enrolled. Methods: Pts were randomised 1:1 to pmab 6.0 mg/kg Q2W+FOLFIRI (Arm 1) vs FOLFIRI alone (Arm 2). Pts had one prior fluoropyrimidine-based chemotherapy regimen for mCRC and ECOG 0-2. The co-primary endpoints were PFS (central assessment) and OS, and were independently tested. Secondary endpoints included objective response rate (ORR), and safety. KRAS status was determined by a blinded central lab. Results: 1,186 pts were randomised and received treatment (tx): 591 in Arm 1, 595 In Arm 2. 1,083/1,186 pts (91%) had KRAS results. Adverse event rates were consistent with the primary analysis. Results are shown in the table . Conclusions: In Arm 1, PFS (standard and on-treatment definition) and ORR were improved, and there was a trend toward improved OS in pts with WT KRAS mCRC. The large proportion of pts receiving post-progression anti-EGFR therapy may have affected the ability to observe a difference in OS between the tx arms. In pts with MT KRAS there was no difference in efficacy. KRAS testing is critical to select appropriate pts for tx with pmab. [Table: see text]
Interaction between intratumoral ERCC1 expression and adjuvant treatment with S-1 on the survival of patients enrolled in the ACTS-GC study.
Authors: Kitada Koji , Ochiai Atsushi , Ichikawa Wataru , Terashima Masanori , Kurahashi Issei , Sakuramoto Shinichi , Katai Hitoshi , Sano Takeshi , Imamura Hiroshi , Sasako Mitsuru 
Published: February 2017

53 Background: Excision repair cross-complementing group 1 (ERCC1) is thought to be involved in resistance to platinum-based therapy. Recently, expression of this gene was shown to be associated with the outcome in patients with gastric cancer. Biomarker analysis was conducted to evaluate the influence of this gene expression on the outcomes of patients enrolled in the ACTS-GC study, a randomized phase III trial, which demonstrated the efficacy of adjuvant treatment with S-1 after D2 dissection for stage II and III gastric cancer (Sakuramoto et al., NEJM 2007). Methods: Formalin-fixed paraffin-embedded specimens were available for 829 of a total of 1,059 (78.3%) patients. ERCC1 expression was measured by RT-PCR in the macrodissected tumor specimens and normalized to β-actin expression as the reference gene. The expression of ERCC1 was categorized into low and high values at the median. Results: The ERCC1 expression level was quantifiable in 97% of the 829 specimens and the distribution was balanced across the arms. In the S-1 group, overall survival (OS) tended to be longer in the high ERCC1 expression group than in the low ERCC1 expression group (HR, 0.698; 95% CI, 0.469-1.040; p= 0.076). On the contrary, in the surgery group, the OS was shorter in the high ERCC1 expression group than in the low ERCC1 expression group (HR, 1.216; 95% CI, 0.881-1.679; p= 0.232), although the difference was not statistically significant. The HR for OS of S-1 to surgery alone was smaller in the high-ERCC1 (HR, 0.465; 95% CI, 0.320-0.678) than in the low-ERCC1 group (HR, 0.805; 95% CI, 0.568-1.141). Significant interaction between the S-1 group and ERCC1 expression was observed (p= 0.033). Conclusions: This large biomarker study showed that intratumoral ERCC1 gene expression may be a predictive marker in gastric cancer patients receiving postoperative adjuvant chemotherapy with S-1.
A novel potential biomarker to monitor treatment response in gastric cancer.
Authors: Maturana Maria J. , Garrido Marcelo , Medina Lidia , Slako Milenko , Funke Ricardo , Acevedo Francisco , Giraldo Claudia , Sanchez Marianela , Munoz Cesar , Corvalan Alejandro 
Published: February 2017

55 Background: Gastric cancer (GC) is the second leading cause of death from cancer worldwide. No clinical useful biomarkers that detect early gastric cancer and have prognostic/predictive value are available. DNA methylation of promoter region of Reprimo (RPRM), a p53-dependent G2 arrest mediator candidate gene, has been postulated as a potential biomarker for early diagnosis of GC (Clin Cancer Res. 2008;14:6264-9). Since RPRM has been found methylated in more than >90% of GC cases, we evaluate RPRM as a biomarker for monitoring response to treatment. Methods: We enrolled 28 patients with GC. Staging classification was carried out by AJCC system and evaluation of clinical response by RECIST criteria. DNA was obtained from plasma/serum by Proteinase K/quiagen and bisulfite converted by EZ DNA Methlyation Direct Kit (Zymo Research). Absolute quantification of DNA Methylation in serum/plasma of RPRM was performed by MethyLight technology. The IRB of PUC approved this study. All patients gave informed consent. Results: Among 28 patients with histological diagnoses of GC, average age was 64 y.o.(38-81 y.o.), male/female ratio 1.3/1, number of cases stage I 2, stage II 4, stage III 8, stage IV 13 and In situ or with preneoplastic lesions 3 patients. 13 patients underwent total gastrectomy and 19 cases received standard chemotherapy (CHM), 6 of them on a neoadjuvancy basis. At initial diagnoses, RPRM was detected in 67,8% (19/28) of patients (X 1049,7 copies per mL[49-11991]). 79% of patients had an objective response with one patient developing a complete response. In cases with clinical response, and at least two detections of RPRM, agreement was 81% with RPRM levels. At the end of study, one third of the patients finally died of gastric cancer. Interestingly, the average initial level of RPRM was higher on those with a fatal outcome (1822 vs 483 copies per mL). The two highest levels were seen on patients who developed a rapid progressive disease and died within months of diagnosis. Conclusions: RPRM could be a potential biomarker to monitor treatment-response in GC. Levels of RPRM may anticipate clinical progression. All these findings should be evaluated in a large, prospective clinical trial.