bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stereotactic body radiation therapy (SBRT) combined with chemotherapy for locally advanced pancreatic adenocarcinoma.
Authors: Gurka Marie Kate , Kim Christine M , Haddad Nadim G , Carroll John , Charabaty Aline C , Jackson Patrick G , Harter K. William , Hwang Jimmy J. , Weiner Louis M. , Marshall John , Collins Sean P. , Pishvaian Michael J. , Unger Keith Robert 
Published: February 2017

361 Background: The role of conventionally fractionated radiation therapy in the management of locally advanced pancreatic cancer (LAPC) is controversial. One concern about concurrent chemoradiation relates to the timing of systemic chemotherapy. In contrast to conventional radiation therapy, SBRT delivers high doses in a shorter duration resulting in minimal disruption in chemotherapy. Here we report our results of patients treated with SBRT and chemotherapy for LAPC. Methods: Twenty-seven patients treated with SBRT for LAPC at our institution from January 1, 2008 to December 31, 2012 were included in this retrospective analysis. Treatment was delivered in 5 fractions of 5 or 6 Gy per fraction in one week. The PTV included the pancreatic mass plus adjacent vasculature in most patients. The majority of patients received concurrent chemotherapy. Median time from diagnosis to SBRT was 1.9 months. Toxicities were scored using the CTCAE v.3. Survival was calculated using the Kaplan-Meier method. Results: The median age was 63 (range 45 – 90). ECOG performance status ranged from 0 – 2 and median Charlson Comorbidity Index was 3, range 0 – 7. All patients completed radiation as prescribed except one, who is excluded from survival analysis. Twenty-five patients received concurrent chemotherapy: 18 received gemcitabine, 6 received mFOLFOX and 1 received capecitabine. Two other patients received sequential chemotherapy. At the time of this analysis, 25 patients had died and the median OS from diagnosis was 13 months. Median PFS was 8.7 months. The first site of radiographic failure was local in 2 patients, local and distant in 1, and distant in 17. Of the other 7 patients, most died after clinical deterioration with no evidence of progression at last imaging. Acute toxicity was minimal. Severe late SBRT-related toxicities included one grade 4 biliary stricture and a grade 5 gastric hemorrhage without prior radiographic tumor progression. Conclusions: SBRT combined with gemcitabine or 5-FU based chemotherapy for LAPC is convenient, feasible and generally well tolerated. The outcomes of SBRT combined with chemotherapy compare favorably to the results of treatment with chemotherapy and conventional RT.
Natural history of untreated patients who had metastatic biliary tract cancer (BTC) with good performance status (PS).
Authors: Kang Jung Hun , Park Se Hoon , Lee Su Jin , Ji Jun Ho , Lee Soon Il , Oh Sung Yong , Hwang In Gyu , Song Haa-na 
Published: February 2017

362 Background: Although chemotherapy is widely recommended to the patients with metastatic biliary tract cancer, the natural course of those group, especially with good PS who are indicated for chemotherapy was rarely known. Methods: We retrospectively reviewed metastatic or distant relapsed BTC patients seen between January 2005 and August 2011 at four cancer centers. Patients were eligible if they had good PS (ECOG 0-2), no history of surgery, chemotherapy, radiotherapy or any treatment for cancer. Results: A total of 1302 patient cohort was identified for metastatic or distantly relapsed BTC and 959 patients were categorized for non-treatment group, 343 patients for treatment group. Of 959 patients, 131 patients were eligible for inclusion criteria and 737 patients were excluded for referral to other hospitals or lost followup, 89 patients for poor PS. The patient demographics were median age of 71 (range:39-89) and male predominant (n=81, 61.8%). Extrahepatic cholangiocarcinoma (n=55, 42.0%) was the most common site of eligible BTC followed by intrahepatic cholangiocarcinoma (n=42,32.1%). Median overall survival was 6.0 months (95% confidence interval [CI];4.9-7.1 months). Univariate analysis showed significant difference of survival depending on the serum level of CA19-9 (CA19-9≥100; 8.2 months vs CA19-9<100;4.4 months, log-rank p-value<0.001). Another potential prognostic factors including age, sex, PS, leucocytosis, serum albumin, CEA level and bile drainage did not have statistical difference in survival. Multivariate analysis showed that elevated 19-9 level was an independent poor prognostic factor(p<0.001, odd ratio, 2.8; 95% CI;1.8-4.8). Conclusions: Metastatic BTC patients with good PS had modest survival. However, patients with normal CA19-9 level showed favorable survival. Further studies comparing chemotherapeutic effect with best supportive care in those group are warranted.
FOLFIRINOX in the real-world setting: The multicentric experience of six Canadian institutions.
Authors: Amireault Carl , Beaudet Julie , Gaudet Guylaine , Raymond Nicolas , Ayoub Jean-Pierre M. , Letourneau Richard , Loungnarath Rasmy , Tehfe Mustapha , Aubin Francine 
Published: February 2017

367 Background: FOLFIRINOX has emerged as a new standard for patients with performance status ECOG 0-1 in metastatic pancreatic cancer and non-randomized studies also support this regimen in locally advanced disease. This regimen is however associated with significant toxicity. The purpose of this study was to assess efficacy and toxicity outside of a clinical trial, including community hospitals. Methods: We conducted a retrospective study of patients with pancreatic adenocarcinoma who received FOLFIRINOX between January 2011 and June 2013 in six institutions in the province of Quebec, Canada. Patients' characteristics, objective response, survival and toxicities were collected. Results: Forty-six patients were included (23 metastatic and 23 locally advanced). Median age was 59 years. Tumor was localized at the head in 65% of patients and 41 % had a biliary stent. Median overall survival was 12,6 months and survival at one year was 61% for metastatic patients. Survival at one year was 95% for locally advanced pancreatic cancer patients and no one with locally advanced tumor became candidate for curative surgery after FOLFIRINOX. Hospitalization rate was 54% with sepsis being the leading cause. There were three treatment-related deaths (7%) and two of them occurred after the first cycle. Neutropenia grade ≥ 3 was observed in 33% of patients and four patients had febrile neutropenia (9 %) with 61% of patients receiving colony stimulating factors (CSFs) for primary prophylaxis. Three patients had cholangitis and diarrhea grade ≥ 3 occurred in 15% of patients. Five patients (11%) experienced transient dysarthria during Irinotecan administration. Conclusions: Survival in our cohort is comparable with data reported by previous studies. However, toxicities were significant and higher than reported. These data highlight the importance of patient selection and support the universal use of CSFs in this population.
A treatment planning evaluation of protons versus IMRT in pancreatic cancer: A comparative study.
Authors: Slater Jerry Monroe , Ling Ted Chen-Tai , Nookala Prashanth , Mifflin Rachel , Grove Roger , Ly Anh , Patyal Baldev , Slater Jerry D. , Yang Gary 
Published: February 2017

369 Background: The purpose of this study is to investigate dose distributions of proton and intensity-modulated radiation therapy (IMRT) photon treatment plans in patients with resected pancreatic adenocarcinoma, focusing specifically on dose reduction to the kidney, liver, and small bowel as organs at risk. Methods: Ten patients with pancreatic head adenocarcinoma underwent Whipple procedure between 2010 and 2013 were included in this study. Most of the patients had locally advanced disease (T3-4N1). All patients were simulated with contrast-enhanced CT imaging. The clinical target volume (CTV) consisted of the pre-operative extent of tumor plus a 10 mm manual expansion in all directions. The planning target volume (PTV) was generated by a further expansion on the CTV ranging from 10-15 mm. A dose of 50.4 Gy given in 28 fractions was delivered to the PTV. All plans were optimized to allow 95% isodose coverage of at least 95% of the PTV. Dose-volume histograms, conformity index (CI), uniformity index (UI), homogeneity index (HI), were calculated and analyzed in order to compare plans between the two modalities. The OAR being evaluated in this study are the kidneys, liver, small bowel, and spinal cord. To determine statistical significance, ANOVA and two-tailed paired t-tests were performed for all data parameters. Results: The proton plans resulted in a lower mean kidney dose (3.17 Gy vs. 9.59 Gy, p=0.039), a lower dose delivered to 1/3 of the liver, D1/3, (0.25 Gy vs. 4.56 Gy, p=0.003), and a lower mean liver dose (1.83 Gy vs. 5.24 Gy, p=0.021). See table for a summary of the results. Conclusions: For patients receiving postoperative radiotherapy for pancreatic cancer, the proton plans are technically feasible and dosimetrically appealing with superior organ at risk sparing compared to IMRT photon treatment plans.[Table: see text]
Impact of postoperative intra-abdominal infection on tumor recurrence and survival in hepatocellular carcinoma after curative liver resection.
Authors: Ruan Dan-yun , Li Yang , Lin Ze-Xiao , Wu Dong-Hao , Wang Tian-tian , Li Xing , Jiang Nan , Wu Xiang-Yuan 
Published: February 2017

374 Background: Postoperative intra-abdominal infection has been reported contributed to higher tumor recurrence rate and poor survival in cancer patients. The study aims to evaluate the impact of postoperative intra-abdominal infection on recurrence free survival (RFS) and overall survival (OS) in patients undergoing curative liver resection for hepatocellular carcinoma (HCC). Methods: ALL patients underwent liver resection from 2003 to 2010 were identified. The Clavien–Dindo (CD) classification was adopted to classify the complications and patients who died of postoperative complications within 30 days of surgery (grade V) were excluded form the study. Univariate and multivariate analyses were used to assess variables. Results: 215 patients were included, the overall 30-day postoperative complication rate was 36.74% (n=79), 13.95% (n=30) were intra-abdominal infectious complication. Patients with intra-abdominal infection had worse RFS (27.6% vs 50%, p<0.001) and OS (46.7% vs 82.2%, p<0.001) than those without it. In multivariate analyses, postoperative intra-abdominal infection was an independent prognostic factor of tumor recurrence (hazard ratio = 2.183; 95% confidence interval, 1.334-3.573) and overall survival (hazard ratio = 4.990; 95% confidence interval, 2.643-9.420). Hepatitis B surface antigen positive, tumor diameter (>5cm) and Child-Pugh class (B) were other three independent factors associated with poor prognosis. Conclusions: According to the study, postoperative intra-abdominal infection predicts tumor recurrence and poor survival after radical liver resection in HCC patients. These findings may have implications of the potential association between inflammatory response and cancer progression.
Pretreatment [18F] FDG-PET texture analysis to predict local response of pancreatic cancer to radiotherapy.
Authors: Tuli Richard , Fraass Benedick , Yang Wensha , Sandler Howard Mark , Hendifar Andrew , Nissen Nicholas N. , Yue Yong 
Published: February 2017

375 Background: Accurate assessment of radiographic response following radiotherapy (RT) for pancreatic adenocarcinoma is challenging. Morphologic and textural features of FDG-PET have been shown to correlate with pathologic response and clinical outcomes in other solid tumors (PMID 23204495). The goal of this study was to develop a predictive algorithm derived from textural features of PET scans to predict response to RT. Methods: With IRB approval, we reviewed 10 patients with locally advanced pancreatic cancer treated with stereotactic body radiation therapy (25-30 Gy in 5 daily fractions). 18FDG-PET/CT scans were obtained 2 weeks pre-RT and 6 weeks post-RT. Pre-RT PET/CT images were deformably registered to the RT planning CT. Tumor volumes of interest were divided into (4.8mm)^3 subvolumes and characterized by mean SUV uptake, RT dose and comprehensive texture analysis. These pre-RT variables were correlated to post-RT mean SUV to identify potential predictors of treatment response. Response prediction was modeled by logistic regression with the Lasso algorithm and validated by 10-fold cross-validation. Model performance was assessed using cross-validated area under the receiver operating characteristic curves (AUC). Results: Mean uptake, RT dose and 6 texture features (energy, correlation, variance, sum mean, cluster tendency, and inverse variance) on pre-RT PET scans were significant in predicting treatment response (AUC 0.85). Within this model, each of the above noted variables was predictive of post-RT response (p<.05). Conclusions: Subvolume-based metabolic and texture features of pre-treatment PET scans were predictive of response following RT. Studies are ongoing to further correlate these variables to RECIST and pathologic response. This should serve as a useful model to help direct response-driven adaptive radiotherapy in patients with locally advanced pancreatic cancer.
18F-FDG PET as a predictor of resectability and clinical outcomes in locally advanced pancreatic cancer patients treated with radiotherapy.
Authors: Tuli Richard , Yang Wensha , Tighiouart Mourad , Yue Yong , Fraass Benedick , Sandler Howard Mark , Hendifar Andrew Eugene , Nissen Nicholas N. 
Published: February 2017

378 Background: Surgical resection is the preferred approach for localized pancreatic adenocarcinoma, yet likelihood of margin positive resection precludes its use in patients with locally advanced (LAPA) disease. Whereas CT imaging is the standard for defining resectability, studies suggest reduced accuracy following radiotherapy (RT). Given the potential clinical implications, improved methods to define resectability are needed. We investigate whether PET and other clinical factors can be used to predict likelihood of margin negative resection in LAPA patients. Methods: We reviewed LAPA patients treated with RT from 2011-2013 who also underwent pre- and 6-week post-RT PET/CT. Mann-Whitney test and Cox modeling were used to identify predictors of margin negative resection and progression-free survival (PFS), respectively. Variables assessed included: pre- and post-RT SUV max, mean, coefficient of variation (CV), total lesion glycolysis, CA19-9 and tumor size. Results: Eighteen LAPA patients treated with RT were identified. Median age was 66 years. Seven were considered resectable following RT. 6 patients underwent margin negative resection, while the 7thpatient refused surgery. An additional 2 patients were technically resectable, but developed metastatic disease. Mean value for post-RT SUV max was 3.5 in resected patients versus 4.9 in unresected patients. This difference was borderline significant (p=.08) for predicting resectability. Similarly, pre- to post-RT change in SUV max was -4.37 in resected patients and -1.26 in unresected patients, which was also not significant (p=.17). Median PFS was 13 months for resected patients and 8.5 months for unresected patients (p=.06). Predictors of PFS included post-RT SUV CV (p=.05) and pre-RT CA19-9 (p=.03). Conclusions: Mean post-RT SUV max was borderline significant for predicting which LAPA patients may undergo successful margin negative resection. Post-RT metabolic response was also predictive of improved PFS, further validating PET/CT as an important prognostic imaging tool. Studies are ongoing to further validate these predictors of resectability given the potential clinical significance.
Influence of histologic subtype on metastatic pattern in colorectal cancer.
Authors: Hugen Niek , Van De Velde Cornelis J. H. , de Wilt Johannes H. W. , Nagtegaal Iris D. 
Published: February 2017

395 Background: In colorectal cancer (CRC) mucinous adenocarcinoma (MC) and signet-ring cell carcinoma (SRCC) have been associated with differences in metastatic patterns compared to the more common adenocarcinoma (AC). This study systematically evaluates metastatic patterns of different histological subtypes and analyses metastatic disease based upon primary tumor localization. Methods: A nationwide retrospective review of pathological records of 5,813 patients diagnosed with CRC who underwent an autopsy between 1991 and 2010 was performed. Patients were selected from the Dutch Pathology Registry (PALGA). To validate metastatic patterns in rectal cancer patients, data was compared to the prospective randomized multicentre TME-trial that investigated efficacy of preoperative radiotherapy. Results: In the autopsy study 1,675 patients with CRC had metastatic disease. Metastatic disease was more frequently found in MC and SRCC than in AC (33.9%, 61.2% and 27.5%; P< 0.0001) and more often had metastases at multiple sites (58.6% and 70.7% versus 49.9%; P=0.001). AC more commonly metastasized to the liver compared with MC and SRCC, 73.0% versus 52.2% and 31.7% (P<0.0001). The occurrence of metastases exclusively to the liver was less common in MC and SRCC patients. In SRCC patients, liver metastases were almost always observed in combination with other metastases. MC and SRCC metastasized to the peritoneal surface frequently, 48.2% and 51.2%, compared with 20.1% in AC (P<0.0001). Colon cancer patients presented more frequently with intra-abdominal metastases, than rectal cancer patients. Rectal cancer patients presented more often with extra-abdominal metastases. Results from the TME-trial confirmed findings in rectal cancer patients from the autopsy study. Conclusions: There are profound differences in metastatic patterns between different histological subtypes and the localization of the primary tumor in CRC. Findings from this study should encourage to take histological subtype into account during pre-operative examination for metastases and during follow-up. Results also indicate that these factors should be considered a stratification factor in future research initiatives focusing on advanced disease.
Overlapping phenotypes with AFAP and FAP in patients with Lynch syndrome gene mutations.
Authors: Heckaman Erin , Moyes Kelsey , Arnell Christopher , Landon Michelle , Wenstrup Richard J. 
Published: February 2017

402 Background: Lynch syndrome is a well-described cause of hereditary colon cancer. A point of the Amsterdam II criteria, which defines Lynch syndrome, is to exclude familial adenomatous polyposis (FAP). FAP is caused by mutations in the APC gene and is defined as the presence of 100+ adenomas. The attenuated form of familial adenomatous polyposis (AFAP) can be considered when an individual has 10-99 adenomas. While adenomatous polyps may be a part of the Lynch syndrome phenotype (as a precursor to carcinoma), the assumption is that Lynch syndrome and APC-associated polyposis do not have overlapping phenotypes. Methods: A retrospective analysis was performed on 8,202 individuals with a personal history of adenomatous polyps that had clinical genetic testing for Lynch syndrome (including genes MLH1, MSH2, MSH6, PMS2, and EPCAM) between January 2006 and July 2013. Patient adenoma history was collected on the test request form. The inclusion criterion was limited to personal history of adenomatous polyps and did not depend on personal or family history of cancer. Patients were excluded if the test performed was either targeted mutation testing or single gene testing, presumably based on prior immunohistochemistry tumor testing. Results: Of 8,202 patients with a personal history of adenomatous polyps that underwent Lynch syndrome testing, 610 (7.4%) were positive for a mutation. Mutations were detected in patients with a wide distribution of cumulative adenomas (Table). Seventy-five of the patients with a Lynch syndrome mutation had an adenomatous polyp phenotype suggestive of either FAP (100+ adenomas) or AFAP (10-99 adenomas). Of these 75 patients, 19 underwent APCtesting, all of whom were negative for a mutation. Conclusions: Individuals with an adenoma history, who were tested for Lynch syndrome, had an overall 7.4% mutation positive rate, indicating an overlapping phenotype between Lynch syndrome and FAP/AFAP. This overlap supports consideration of a gene panel test approach. [Table: see text]
Identifying BRAF mutations in colorectal cancer (CRC) by initial immunohistochemical (IHC) staining for mismatched protein expression as part of a Lynch syndrome screening program: A distinct clinicopathologic entity.
Authors: Grote Thomas H. , Kilpatrick Scott E. , Webb Dena B. , Hughes Amy Herndon , Hughes Sarah 
Published: February 2017

405 Background: Multiple genetic mutations resulting in different clinical phenotypes have been found in colorectal adenocarcinoma. Mutation in the BRAF oncogene is a key step in malignant transformation within the methylator pathway leading to colorectal cancer. There is little data regarding the identification of the subset of CRCs exhibiting mutations in the BRAF oncogene with initial IHC staining, as well as a paucity of information describing this unique subset of colorectal cancers Methods: Between 1/1/11 to 12/31/12, all newly diagnosed CRCs underwent IHC testing for MLH1, MSH2, MHS6, and PMS2 protein expression if sufficient pathologic material existed. If MLH1 protein expression was absent, BRAF V600E mutation analysis was preformed. Patient demographics, pathology and outcomes were examined through chart review. Statistical associations were determined by the TTest, Fisher’s exact probability test and Cox regression analysis of Kaplan-Meier curves. Results: 314 newly diagnosed CRC patients were identified and 278 (89%) underwent IHC staining (study population). 48 had absent MLH1 protein expression (15%) and underwent BRAF mutational analysis. 35/48 had the V600E mutation. Comparing the BRAF mutated group to the study population without BRAF mutation showed statistically significant differences. These differences included median age at diagnosis (78 vs. 65 years, p < 0.0001), female sex (77% vs. 51%, p = 0.0037), right colon location (77% vs. 42%, p = 0.0001) and significant mucinous component denoted pathologically (31% vs. 7%, p = 0.0001). There was no difference in stage of CRC at diagnosis between the groups. Survival rates at one year based on Kaplan Meier curves were 65% vs. 82% and results will be updated. Conclusions: BRAF mutations in CRC are associated with unique clinicopathologic characteristics and overall worse prognosis. This subgroup of CRC can be identified as part of a Lynch Screening program via ICH staining of the mismatch repair proteins MLH1, MSH2, MSH6, and PMS2.