bluuebunny/crossref_metadata_2025_split huggingface dataset:
BAP1 mutation-associated cholangiocarcinoma: An aggressive disease.
Authors: Anand Deepa , Churi Chaitanya , Rashid Asif , Shroff Rachna T. , Zuo Mingxin , Conrad Claudius , Vauthey Jean-Nicolas , Javle Milind M. 
Published: February 2017

420 Background: BRCA-associated protein-1 is a deubiquitylating enzyme encoded by the BAP1 gene, which is commonly mutated in uveal melanoma, mesothelioma and renal cancers. BAP1 mutations predict an aggressive disease course in these tumors. Recent data indicate that BAP1 mutation is also present in cholangiocarcinoma (CCA). The clinical phenotype of CCA with BAP1 mutations has not been defined. We investigated the clinico-pathologic features and treatment outcomes of these patients treated at a single center. Methods: A comprehensive chart review of CCA patients who had undergone genomic testing was performed. Data collected included clinical, pathological, genetic and radiological features and response to therapy. Results: Nine cases of BAP1 mutation associated CCA were diagnosed from January 2009 to May 2014 (Table). Seven patients had intrahepatic CCA and two had extra-hepatic CCA. Tumor size ranged from 6 to 14.7 cm (mean = 8.7 cm). Seven patients had poorly differentiated carcinoma whilst the other two had moderately differentiated tumors. Out of the nine patients, seven had nodal metastases and six had satellite lesions in liver. Six patients had distant metastases at presentation. Sites of metastases were bone, peritoneum, lung and abdominal wall. All nine patients showed progressive disease following primary therapy (primary chemotherapy or neoadjuvant chemotherapy after primary surgery). The average time to tumor progression after first therapy was 3 months. Conclusions: BAP1 mutation in CCA may be associated with an aggressive prognosis and poor response to standard therapies. [Table: see text]
Does the addition of adjuvant intraoperative postdissection tumor bed chemotherapy during GI neuroendocrine tumor debulking benefit patients?
Authors: Wang Yi-Zarn , Chauhan Aman , Ramirez Robert A , Stevens Melissa A , Boudreaux J Philip , Woltering Eugene , Anthony Lowell Brian 
Published: February 2017

442 Background: Midgut neuroendocrine tumor (NET) patients are often diagnosed at an advanced stage with extensive mesenteric lymph node and liver metastasis. The only treatment for potential cure and durable results is resection with extensive debulking. However, even with the most elegant surgical dissection/resection, macro and microscopic residual disease at the tumor resection bed remains a distinctive possibility. We hypothesize that local application of 5-florouracil (5-FU) within tumor bed would eliminate the microscopic residual disease post operatively. Methods: Surgical records of 188 consecutive patients who underwent extensive cytoreductive surgeries for stage IV, small bowel NETs with boggy mesenteric lymphadenopathy between 2003-2012 were reviewed. 85 Patients who had 5-Florouracil saturated gelfoam strips secured into their mesenteric resection defects served as the study group (n=85) with one hundred three patients who did not receive such intra-operative chemotherapy as the control (n=103). Survival from the time of diagnosis, postoperative morbidity and mortality between the two groups were collected and compared. Results: Mortality rates at immediate, 30, 60 and 90 days post operative period were 3; 0; 1; 0; and 0; 2; 0; 4 respectively for study and control group. Minor complications (Clavien-Dindo Grade I and II) at 30, 60 and 90 day postoperative period were 12; 0; 1 and 12; 5; 5 respectively. Major complications (Grade III and IV) at the same time intervals were 2; 0; 2 and 2; 3; 2 for study and control groups. Most of all, the mean survival from time of histological diagnosis for the study patients was 210 months (17.5 years) as compared to 177 months (14.7 years) for the control group with a difference of 33 months (2.75 years). Conclusions: Intra-operative tumor resection bed chemotherapy is a safe adjuvant without any discernible toxicity. Furthermore, it might provide survival benefit to midgut NET patients with extensive mesenteric lymphadenopathy undergoing extensive cytoreductive surgery without additional procedure related complications.
A tertiary cancer center experience with yttrium-90 radioembolization in hepatocellular carcinoma.
Authors: Schaffer Kerry , Noel Marcus Smith , Hezel Aram F. , Katz Alan W. , Sharma Ashwani , Baran Andrea , Connolly Gregory Clayton , Tejani Mohamedtaki Abdulaziz 
Published: February 2017

443 Background: Local-regional radioembolization with Yitrium-90 (Y-90) has become standard practice for patients with hepatocellular carcinoma (HCC) either as a bridge to transplant, or for local disease control. Outcomes data in the United States are limited and here we review our institutional experience with Y-90 radioembolization. Methods: We retrospectively reviewed charts from 70 patients with HCC who were treated with Y-90 from May 2010- January 2014. Clinical variables including Child-Pugh class and CLIP score were extracted from patient records. The Cox proportional hazards model was used to determine prognostic factors, and Kaplan-Meier curves were used to determine PFS and OS. Results: Median age was 61 (range 43-82), 79% Caucasian, 84% male, and 79% Child-Pugh class A. Median progression free survival (PFS) was 8.4 months (95% CI 6-10.7) and overall survival (OS) was 14.2 months (95% CI 9.7-21). Overall survival significantly differed by Child -Pugh score (p= 0.009), CLIP score (p=0.003), and presence of portal vein thrombosis (PVT) (p=0.0384), based on the log-rank test comparing Kaplan-Meier curves. Using univariate Cox proportional hazards models, both elevated baseline AFP, measured on a log scale (HR 1.79, 95% CI 1.32-2.43, p=0.0002) and post Y-90 treatment with sorafenib (HR=2.30, 95% CI 1.07-4.95, p=0.03) were associated with worse mortality. Elevated AFP (HR 2.45, 95% CI 1.73-3.47, p<0.0001) and Child-Pugh score of B (HR 4.83, 95% CI 2.23-10.43, p<0.0001) were associated with worse mortality in a multivariate Cox model adjusting for age and ethnicity. Furthermore, AFP values were significantly higher in the 10 patients who died within 4 months of Y-90 (p=0.001), and significantly lower in 7 patients who eventually received a liver transplant (p=0.0002). Conclusions: In patients undergoing treatment with Y-90 radioembolization, Child-Pugh class, CLIP score, presence of PVT, baseline AFP, and sorafenib post Y-90 were significantly associated with overall survival. Median PFS and OS data in this institutional cohort are encouraging. Further prospective studies on Y-90 treatment for HCC are warranted.
Stereotactic body radiotherapy (SBRT) reirradiation for recurrent pancreas cancer.
Authors: Dagoglu Rabia N , Callery Mark , Moser James , Tseng Jennifer F. , Kent Tara , Bullock Andrea J. , Miksad Rebecca A. , Mancias Joseph Douglas , Mahadevan Anand 
Published: February 2017

451 Background: After adjuvant or definitive radiation for pancreas cancer, there are limited conventional treatment options for recurrent pancreas cancer. We explored the role of (Stereotactic Body Radiotherapy) SBRT for reirradiation of recurrent pancreas cancer. Methods: Our institutional IRB approved database was retrospectively reviewed. All patients were deemed unresectable and treated with systemic therapy. Fiducial gold markers were used. CT simulation was performed with oral and IV contrast and patients were treated with respiratory motion tracking.The choice of fractionation was based on tumor volume, location of the tumor and prior radiation dose, interval between prior RT, adjacent normal tissue, patients’ performance status and co morbidities. The irradiation dose was prescribed to the isodose line covering at least 95% of the target volume. Maximum point dose to the gastric and duodenal walls was kept at or below prescription dose. Results: This study included 30 patients reirradiated for recurrent pancreas cancer at our center between September 2005 and September 2013. 17 males and 13 females were treated. The median age at the time of reirradiation was 67 years (range 44 to 88 years). Median follow-up was 11 months (4 to 24 months).The median target volume was 41.29cc. The median prescription dose was 25Gy (24-36 Gy) in a median of 5 fractions prescribed to a mean 78% isodose line. The median overall survival was 14 months. The 1 and 2 year local control was 78%. The worst toxicity included 3/30(10%) grade III acute toxicity for pain, bleeding and vomiting. There was 2/30 (7%) Grade III long-term bowel obstructions. Conclusions: Management of locally recurrent pancreatic cancer, particularly after prior radiation therapy, is challenging. We report the utility of SBRT for reirradiation of locally recurrent pancreas cancer after prior radiation, with reasonable local control, modest survival and acceptable toxicity. Future prospective studies are needed to define the role of SBRT reirradiation for local recurrences in the setting of systemic therapy.
Quality of life (QOL) in patients with pancreatic and periampullary adenocarcinoma (PPAC).
Authors: Sheng Jennifer , Wai Christina , Fang Carolyn Y , Devarajan Karthik , Huang Christine , Hoffman John Parker , Denlinger Crystal Shereen 
Published: February 2017

454 Background: QOL includes perceived well-being, symptom burden, satisfaction, and enjoyment of normal activities. Limited data exist on QOL and long-term treatment effects in PPAC survivors. We evaluated factors that may impact QOL. Methods: Cross-sectional study (survey and chart review) of QOL, fear of recurrence, symptom burden, nutritional factors, and physical activity in disease free stage 0-III PPAC pts who completed treatment ≥ 12 months between 1990-2013. Pts identified via Tumor Registry and institutional database. Survey scales: FACT-Hep, Fear of Cancer Recurrence Inventory (FCRI), FACIT-AD, Hepatobiliary Symptom Index (FHSI-8), Godin Leisure Time Score (GLTS), Cancer Appetite and Symptom Scale (ASQ), and pancreatic enzyme use. Dillman mailed survey method used. Chart review yielded demographics, PPAC stage, therapy received, enzyme use, and comorbidities. Results: Of 90 identified pts, 78 mailed surveys (10 recurred; 2 died). Response rate 77% (n=60). 45 pts returned consent and survey (2 no consent, 6 opt-out, 7 ineligible). Median age at dx 65 yrs (46-87), at survey 70 yrs (51-89). Male 19/Female 26. Stage 0 (5), I (17), II (22), III (1). Median time from dx to survey 2156 days (385-6333), from surgery to survey 2134 days (343-6280). Mean scores (SD): FACT-Hep 144.5 (19.16), FCRI 51.57 (27.0), FACIT-AD 99.13 (14.47), FHSI-8 26.3 (4.15) and ASQ 34.58 (4.61), consistent with published cohorts. Pts insufficiently active with mean GLTS unit 11 (0-140, SD 25.85). Compared to those without, pts with hypertension (n=27) after surgery were less physically active (9.41 vs 13.61, p=0.046) and pts with diabetes (n=23) had poorer physical well-being (23.39 vs 25.13, p=0.017). Overall QOL was not associated with pancreatic enzyme use, time from diagnosis or surgery, primary tumor site, surgery type or physical activity. Conclusions: Despite small sample size, overall QOL, fear of recurrence, hepatobiliary cancer symptoms, and appetite in our cohort appear similar to other PPAC populations. Pts are insufficiently active, with hypertensive pts at higher risk for inactivity and diabetics with poor physical well-being. Additional evaluation of these in larger cohorts of PPAC survivors is warranted.
Role of second-line gemcitabine after FOLFIRINOX failure in advanced pancreatic adenocarcinoma: A retrospective analysis.
Authors: Lino Aline Da Rocha , Martins Junior Rodnei Merlrina , Abrahao Carina Mina , Moreira Raphael Brandao , Sousa Tarcia Tarciane Soares de , Gomes Jessica Ribeiro , Alessandretti Matheus Bongers , Amarante Marcus Paulo Fernandes , Ferrian Andrea Malta , Schutz Fabio Augusto Barros , Kawamura Carolina , Schmerling Rafael , Cruz Marcelo Rocha , Peixoto Renata D'Alpino , Machado Marcel Cerqueira Cesar , Buzaid Antonio C. , Maluf Fernando C. 
Published: February 2017

473 Background: Cancer of the exocrine pancreas is a highly lethal malignancy. Based on a phase III study, FOLFIRINOX regimen became the standard first-line treatment for patients with good performance status. However, the optimal management strategy for patients who fail initial FOLFIRINOX remains undefined. We aim at reporting our experience with single-agent gemcitabine as a second-line treatment for advanced pancreatic cancer patients who progressed on FOLFIRINOX. Methods: Patients with advanced exocrine pancreatic adenocarcinoma who received gemcitabine (1.000 mg/m² on days 1, 8 and 15 every 4 weeks) until disease progression, as second-line therapy after FOLFIRINOX failure at our institution were retrospectively evaluated. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Results: A total of 20 patients were reviewed. Most of them (60%) had metastatic disease while 40% had locally advanced tumors. Median age was 60 years (range 43–74) and 80% were male. Eastern Cooperative Oncology Group (ECOG) performance status was 0 or 1 in 65% and 2 or 3 in 35% of the patients. Median time on prior FOLFIRINOX therapy was 5 months. Median PFS and OS with gemcitabine were 2,0 (95% CI 1,2-2,8) and 5,7 months (95% CI 3,9-7,4), respectively. There were no deaths due to the treatment. Conclusions: In this study, gemcitabine was a reasonable second-line treatment option for patients with advanced pancreatic adenocarcinoma. Phase III trials are urgently needed exploring the role of gemcitabine in the second-line setting.
Phase 3 clinical Trial Evaluating 90y glass microspheres in patients with metastatic colorectal carcinoma of the liver who have failed first-line chemotherapy.
Authors: Karpf Maria Angela 
Published: February 2017

474 Background: Colorectal cancer (CRC) is the third most common cancer in the US. Half of pts diagnosed with CRC develop liver disease. Unresectable liver metastases are responsible for morbidity/mortality. Typically, pts with metastatic CRC receive an oxaliplatin- or irinotecan-based regimen as first-line chemotherapy, +/- bevacizumab. On progression, pts are treated with the regimen they did not receive during first-line chemo. A study to evaluate yttrium 90 glass microspheres (TheraSphere; 90Y) in pts with unresectable mCRC of the liver showed that pts with good performance status, no extrahepatic metastases, and ≤ 25% tumor may benefit most from 90Y. 90Y glass microspheres are approved by FDA under a Humanitarian Device Exemption (HDE). This study will evaluate outcomes in this patient subset when 90Y is added to second-line SOC chemo. The objective is to evaluate efficacy/safety of 90Y in patients with liver mCRC that has progressed after first-line chemo. Methods: Open-label, multi-center, randomized study to evaluate 90Y treatment in ~340 eligible pts, in whom SOC 2nd-line chemo with either an oxaliplatin or irinotecan-based regimen is planned. Eligible pts will be randomized 1:1 to control or treatment. Treatment pts will receive a first cycle of second-line chemo within 21 days of randomization and at least 14 days after the last dose of first-line agents including VEGF inhibitors. 90Y will be administered in place of the second chemotherapy cycle. Control pts will receive planned SOC second-line chemo. Primary endpoint is progression-free survival. Secondary: overall survival, hepatic progression-free survival, time to symptomatic progression, tumor response rate, and adverse events. Pts will have regular study visits as long as they participate, at which time safety/efficacy data will be collected and recorded. Results: NA Conclusions: Given the potential benefit to mCRC pts, this Phase 3 study will evaluate 90Y in the second-line setting in patients who have progressed following SOC first-line chemotherapy. Clinical trial information: NCT01483027.
Living longer with pancreatic cancer: More than FOLFIRINOX?
Authors: Chae Phillip , Punja Punam , Koutlas Nate , Atluri Prashanti 
Published: February 2017

476 Background: Effective treatment for uresectable locally advanced pancreatic cancer (LAPC) or metastatic pancreatic cancer is limited and has a poor prognosis with a five year survival rate of 6.7%. FOLFIRINOX has been studied as a neoadjuvant therapy for LAPC and has a response rate of 32%. We set out to investigate which factors, if any, have a meaningful impact on time to disease progression within this cohort of patients. Methods: A retrospective chart review was conducted. All patients who recieved FOLFIRINOX at our institution from 2011-2014 were included. 16 of 19 had unresectable LAPC or metastatic disease at time of diagnosis. A few recieved FOLFIRINOX upon first progression after adjuvant therapy. Results: See Table. Conclusions: Novel approaches are being used to get patients to R0 resection if they have borderline resectable pancreatic cancer or unresectable LAPC consisting of combination chemotherapy followed by radiation. Metastatic patients or unresectable LAPC who do not undergo surgery have limited survival. Reviewing our data we found that the addition of radiation in the metastatic setting may impact time to progression as determined by RECIST criteria. Of the three patients who had the longest time to progression, two were metastatic and both underwent palliative RT to the primary pancreatic lesion. Incorporation of RT to the primary lesion upon completion of FOLFIRINOX therapy should be considered as an innovative approach to increase time to progression and potentially progression free survival and overall survival. Clinical trials randomizing selected patients with metastatic or unresected LAPC to FOLFIRINOX followed by RT versus no RT should be considered. [Table: see text]
Is serum HER2-ECD testing significant for resectable gastric cancer?
Authors: Tanaka Tsutomu , Tajika Masahiro , Ishihara Makoto , Mizuno Nobumasa , Hara Kazuo , Hijioka Susumu , Imaoka Hiroshi , Hashimoto Mitsuyoshi , Yatabe Yasushi , Muro Kei , Yamao Kenji , Niwa Yasumasa 
Published: February 2017

48 Background: Accurate assessment of human epidermal growth factor receptor (HER) 2 is essential for patients with gastric cancer (GC) who may benefit from therapies targeting this surface receptor such as trastuzumab. The extracellular domain (ECD) of the HER2 protein may be shed into the serum and is detectable using an enzyme-linked immunosorbent assay. Correlations have been reported between raised baseline ECD levels, suggesting that serum ECD levels may be useful in making treatment decisions in patients with HER2 positive GC. We investigated this relationship in patients with resectable GC. Methods: This retrospective study was conducted in 71 patients with resectable GC between Apr. 2009 and May 2012. We assessed HER2 protein overexpression and gene amplification using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). HER2 positive was defined as IHC 3+ or IHC 2+/ positive FISH. The serum HER2-ECD level was measured using the blood serum before the surgical treatment. We examined the relationship between serum HER2-ECD level, HER2 expression in resected specimens, depth of invasion of cancer, lymph node metastasis, and clinical stage. Results: Baseline values were available in 71 patients, and of these, 2 (2.8%) had raised levels (> 15 ng/mL). Median serum ECD levels was 11.7 (7.5-17.9) ng/mL. Two patients showing high HER2-ECD without HER2 over-expression. No clear relationship was found between baseline ECD levels and HER2 over-expression. Serum HER2-ECD level was not associated with invasion depth and lymph node metastasis, and clinical stage. Conclusions: There is no significance of serum HER2-ECD testing in resectable gastric cancer.
Effects of dose-modified FOLFIRINOX on toxicity and effectiveness in Japanese patients with unresectable pancreatic cancer (PC).
Authors: Uesugi Kazuhiro , Asagi Akinori , Hino Kaori , Nadano Seijin , Iguchi Haruo 
Published: February 2017

480 Background: FOLFIRINOX has been shown superior to GEM in terms of OS, PFS and/or RR for treatment of metastatic PC in Accord 11, and this regimen has become the standard of care for the first-line chemotherapy. However, the major disadvantage of FOLFIRINOX is significantly higher toxicity, and, in particular, quite higher incidence of neutropenia(78%) and febrile neutropenia(22%) was observed in the PII clinical trial of FOLFIRINOX performed in Japan (LOHP-PII-05, JSCO 2013). Thus, in clinical practice for the Japanese patients, it should be needed to make modification on this regimen in terms of dose reduction without compromising in its effectiveness. We evaluated the safety and efficacy of modified(m) FOLFIRINOX in Japanese patients with unresectable locally advanced PC(LAPC) and/or metastatic PC(MPC). Methods: The modifications to FOLFIRINOX include discontinuation of the bolus 5-FU and dose-reduction(25%) of irinotecan. 20 patients with unresectable LAPC and/or MPC (PS 0-1) were treated with m FOLFIRINOX given every 2 weeks, and toxicity and efficacy were evaluated in these patients who received more than 3 courses. All patients did not receive prophylactic filgrastim. Results: Patient characteristics were as follows: LAPC/MPC 4/9; median age 65 yrs(range 39~75); male/female 15/5. Median number of cycles was 5.5 (range 1~17). Grade 3/4 toxicities included neutropenia(25%), nausea(30%), anorexia(35%) and diarrhea(20%). Grade 1/2 toxicities were sensory neuropathy(45%) and vomiting(40%). Febrile neutropenia was noted in 2 patients(10%). Toxic death was not observed, and 12 patients(60%) required dose reduction due to toxicity. Hematologic toxicities were decreased, however, those concerned with gastrointestinal toxicities were observed in a bit higher incidence compared to those in LOHP-PII-05. Response by CA19-9 was evaluable in 11 patients. 9 of 11 patients (82%) showed a decline in CA19-9 levels from baseline, and a greater than 50% decline was noted in 5 of 11 patients(45%). Conclusions: m FOLFIRINOX seems to have an improved safety profile even without prophylactic filgrastim and to maintain its efficacy.