bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stereotactic radiation treatment planning with volumetric modulated arc therapy: Impact of duodenal sparing on pancreatic tumor coverage.
Authors: Kumar R. , Kang J. , Herman J. M. , Tuli R. , Pawlik T. M. , Tryggestad E. , Smith K. , DeWeese T. L. , Wong J. , Ford E. C. 
Published: February 2017

301 Background: Volumetric modulated arc therapy (VMAT) allows for intensity-modulated radiation delivery with faster treatment times and fewer delivered monitor units (MU). The dose-limiting structure for pancreatic stereotactic body radiation therapy (SBRT) is the duodenum. We evaluate VMAT dose distribution, delivery times, and the effect of duodenal sparing (DS) for pancreas SBRT. Methods: Plans of 15 patients with unresectable pancreatic cancer (14 head/1 tail) were selected. VMAT treatment planning with the “SmartArc” function of Pinnacle v. 8.9 was used to plan one fraction of 25 Gy to the PTV (gross tumor + 2 mm expansion) normalized to the 80% isodose line. Two VMAT SBRT plans were conducted for each case; the first did not attempt to spare the duodenum (non DS) while the second did (DS). Constraints were stomach/duodenum any point max <30 Gy (for DS plan), liver D50 < 5 Gy, ipsilateral kidney D25 < 5 Gy, cord Dmax < 5 Gy and stomach D4 < 22.5 Gy. Results: Gross tumor volume ranged from 58.4cm3 to 320.3 cm3. The average overlap volume between PTV and the duodenum was 8.4 cm3. In 10/15 non-DS plans, the duodenal Dmax exceeded 30 Gy. With DS optimization, only 1/15 plans exceeded the 30 Gy threshold. These differences were statistically significant (p<0.001). Typical MU and delivery times, as calculated by the planning software, were 5494 MU and 775 secs vs. 5296 MU and 703 secs for the DS and non-DS plans, respectively. The difference in delivery times was significant (p=0.01), but amounted to only 1.2 min on average. The average duodenal Dmax for non-DS plans was 30.4Gy, D4% was 23.4 Gy. With DS, the average Dmax was reduced to 28.1Gy and D4% to <19.7 Gy (p<0.001). As expected, VMAT plans with greater overlap between the duodenum and PTV had a higher duodenal Dmax. Conclusions: This study demonstrates the feasibility of VMAT for high-dose SBRT treatment of pancreatic cancer incorporating constraints to limit the dose to the duodenum. Future studies will evaluate whether VMAT with fractionated SBRT results in improved duodenal sparing more efficiently than traditional IMRT. No significant financial relationships to disclose.
Concurrent chemoradiotherapy with gemcitabine and S-1 for unresectable locally advanced pancreatic adenocarcinoma: A phase I study.
Authors: Ioka T. , Fukutake N. , Ikezawa K. , Tanaka S. , Nakamura S. , Nishiyama K. 
Published: February 2017

305 Background: The primary objective of this study is to assess the toxicity of concurrent radiotherapy with a combination of gemcitabine (GEM) and S-1 for unresectable locally advanced pancreatic cancer. Methods: Chemotherapy-naive patients with histologically or cytologically proven unresectable locally advanced pancreatic adenocarcinoma were enrolled to this trial. The patients received gemcitabine intravenously over 30 min on days 1 and 8 and S-1 orally b.i.d. from days 1 to 14. Cycles were repeated every 21 days until disease progression. Patients were scheduled to receive gemcitabine (mg/msq/week) and S-1 (mg/msq/day) at five dose levels: 600/50 (level 1), 600/60 (level 2), 800/60 (level 3), 800/70 (level 4) and 1000/70(level 5). Radiation therapy was delivered through four fields as a total dose of 50.4 Gy in 28 fractions over 5.5 weeks, and no prophylactic nodal irradiation was given. Dose-limiting toxicity (DLT) was defined as grade 4 thrombocytopenia, grade 4 neutropenia, or grade 3 nonhematologic toxicity. All patients were evaluated for response with RECIST criteria by a radiologist. Results: Fifteen patients were enrolled in this study between 05/12 and 07/05. Treatment was well tolerated; 14 patients completed all protocol therapy, but one cannot because of anorexia. The maximum-tolerated dose was level 2, Gem 600mg/ S-1 60mg. Six patients experienced DLT (four patients with anorexia and two patients with Gr4 neutropenia). Response rate (RR) was 33.3% and disease control rate was 87.0%. And 1-year and 2-year survival rate was 86.7% and 44.4% respectively. Conclusions: The chemoradiation therapy a combination of gemcitabine (GEM) and S-1 can be delivered almost safely for unresectable locally advanced pancreatic cancer. No significant financial relationships to disclose.
Prognostic factors in patients with advanced hepatocellular carcinoma treated with sorafenib: A comparison with previously known prognostic models.
Authors: Baek K. , Kim J. , Um J. , Park S. , Lee J. , Park J. , Park Y. , Lim H. , Kang W. 
Published: February 2017

323 Background: Sorafenib, a multiple-targeted tyrosine kinase inhibitor, is now the treatment of choice for systemic therapy of patients with advanced hepatocellular carcinoma (HCC). Herein we present the clinical characteristics and outcomes of patients with advanced HCC who were treated with sorafenib. Methods: Data of 201 sorafenib-treated, metastatic HCC patients were collected from a single institution tumor registry. The primary and secondary endpoints were overall survival (OS) and failure-free survival (FFS). Results: Chronic hepatitis B was the predominant cause of HCC (84%).Of 162 evaluable patients, four partial responses were recorded. With a median follow-up of 15.7 months, the median FFS and OS were 2.5 months (95% confidence interval [CI], 2.3-2.7 months) and 5.3 months (95% CI, 4.4-6.3 months), respectively. In multivariate analysis, the prognostic factors associated with FFS were the presence of ascites, portal venous thrombosis, serum alpha- fetoprotein (AFP) ≥400 ng/mL, albumin, bilirubin, tumor size and number, and performance status. Likewise, the presence of ascites, portal venous thrombosis, tumor size and number, performance status, and baseline levels of AFP, albumin and bilirubin were significantly related with OS. After adjusting for performance status, the Cancer of the Liver Italian Program (CLIP) scoring system and Okuda stages can better predict the hazard of failure or death than Child-Pugh classification. Conclusions: Our results suggest that CLIP scores or Okuda stages, along with performance status, can be useful in stratifying patients with advanced HCC treated with sorafenib. No significant financial relationships to disclose.
Potential role of chemoradiotherapy for metastatic pancreatic cancer.
Authors: Lee D. Y. , Robertson J. M. , Huang J. , Margolis J. H. , Balaraman S. , Nadeau L. 
Published: February 2017

344 Background: Patients with metastatic pancreatic cancer have a poor outcome and the radiotherapy is typically only given to patients requiring palliation. We analyzed our institutional pancreas database to compare the outcome between chemotherapy alone vs. chemoradiotherapy. Methods: From January 2000 to December 2008, 199 metastatic pancreatic cancer patients were retrospectively analyzed. 13 (6.5%) patients received chemoradiotherapy and 186 (93.5%) patients received chemotherapy alone. Chemotherapy regimens consisted of 5-fluorouracil, gemcitabine, erlotinib, or cisplatin. The follow-up time was calculated from the time of diagnosis to the date of death or the last contact. Kaplan-Meier analysis was used to calculate the overall survival (OS). Results: Median OS was 5.3 months for all patients. Median OS was 4.9 months (0.4–27.0) for patients treated with chemotherapy alone and 7.8 months (0.6–44.1) for those treated with chemoradiotherapy (p = 0.013). Univariate survival analysis of categorical variables for patients treated with chemoradiotherapy revealed that age, race, gender, location of metastatic site, T stage (T3 v. T4) or nodal stage were not significant. However, ECOG performance status (1 v. 2/3) and the dose of radiation (<35 v. >35 Gy) received were associated with improved survival (p = 0.013, p=0.049). Median OS was 12.9 months for ECOG 1 vs. 5.6 months for ECOG 2/3. Median OS was 11.1 months for patients treated with radiotherapy dose > 35 Gy vs. 5.9 months for those who received less than 35 Gy. 3/13 (23%) patients who received chemoradiotherapy lived nearly two years or more. Conclusions: Metastatic pancreatic cancer patients with good performance score may benefit from chemoradiotherapy. Long-term survival was observed in this selected group. No significant financial relationships to disclose.
Adjuvant FOLFIRI with or without cetuximab in patients with resected stage III colon cancer: NCCTG Intergroup phase III trial N0147.
Authors: Huang J. , Sargent D. J. , Mahoney M. R. , Thibodeau S. N. , Smyrk T. C. , Sinicrope F. , Nelson G. D. , Alberts S. R. 
Published: February 2017

363 Background: Irinotecan (CPT-11) has demonstrated antitumor activity against metastatic colorectal cancer used alone or with 5-fluorouracil (5FU)/leucovorin (LV). Two arms with CPT-11, 5FU, and LV (FOLFIRI) +/- cetuximab (Cmab) were originally included in N0147. However, after CALGB 89803 (J Clin Oncol. 25:3456, 2007), PETACC-3 (J Clin Oncol. 27:3117, 2009), and Accord02 (Ann Oncol. 20:674, 2009) showed no benefit to the three-drug combination in adjuvant therapy, the CPT-11 arms of N0147 were discontinued. We report the outcomes for patients given FOLFIRI +/- Cmab. Methods: Following a signed informed consent patients with resected stage III colon cancer were randomized to one of 6 arms including 12 biweekly cycles of CPT-11 180 mg/m2 d1 with LV 400 mg/m2, 5FU 400 mg/m2 bolus IV, then 46-hr IV 5FU 2,400 mg/m2 on d1-2 without (Arm B, FOLFIRI) or with Cmab (Arm E) 400 mg/m2 d1 cycle 1 then Cmab at 250 mg/m2 d1 and 8. Primary endpoint was 3-year disease-free survival (DFS). Secondary endpoints included overall survival (OS) and toxicity. Results: 156 patients (Arm B-111, Arm E-45) were enrolled; median follow-up on 81 patients in Arm B was 60.3 months and 58.2 months in Arm E for 41 patients. wtKRAS (vs mt) status was associated with improved DFS (HR=0.6 [95% CI 0.4-1.1], p = 0.09) and OS (HR 0.7 [95% CI 0.4-1.5], p = 0.38). The addition of Cmab improved DFS and OS in the overall group and within wtKRAS pts. Grade greater than III non-hematologic adverse effects were significantly increased in the Cmab arm (46% vs. 64%, p = 0.05). Conclusions: In this randomized phase III trial adjuvant FOLFIRI resulted in a 3-year DFS lower than that expected for FOLFOX. Trends for improved DFS and OS with the addition of Cmab were observed in patients with resected stage III colon cancer patients, regardless of KRAS status. Supported by NIH Grant CA25224, Bristol-Myers Squibb, ImClone, Sanofi-Aventis, and Pfizer. [Table: see text] [Table: see text]
Long-term update of U.S. GI Intergroup RTOG 98-11 phase III trial for anal carcinoma: Comparison of concurrent chemoradiation with 5FU-mitomycin versus 5FU-cisplatin for disease-free and overall survival.
Authors: Gunderson L. L. , Winter K. A. , Ajani J. A. , Pedersen J. E. , Benson A. B. , Thomas C. R. , Mayer R. J. , Haddock M. G. , Rich T. A. , Willett C. G. 
Published: February 2017

367 Background: On initial publication of GI Intergroup RTOG 98-11, concurrent chemoradiation with 5FU+mitomycin (MMC) decreased colostomy failure (CF) vs induction plus concurrent 5FU+cisplatin (CDDP), but did not significantly impact disease free or overall survival (DFS, OS). The intent of the current analysis is to determine the long-term impact of treatment on survival (DFS, OS, colostomy-free [CFS]), CF and relapse (local-regional [LRF], distant [DM]) in this patient group. Methods: Stratification factors included gender, clinical node status, and primary size. DFS/OS were estimated univariately by Kaplan-Meier method and treatment arms compared by log-rank test. Time to relapse/CF were estimated by cumulative incidence method and treatment arms compared by Gray's test. Multivariate analyses were done with Cox proportional hazard models to test for treatment differences, adjusting for stratification factors. Results: Of 682 patients accrued, 649 were analyzable for outcomes. As seen in the table, 5-yr DFS and OS were statistically better for RT+5FU/MMC vs RT+5FU/CDDP (67.7 v 57.6%, p=.0.0045; 78.2 v 70.5%, p=0.021) with trends toward statistical significance for CFS, LRF, and CF (71.8 v 64.9%, p=0.053; 20 v 26.5%, 11.9 v 17.3%, p=0.092 and 0.075). Similar results were seen in multivariate analysis. Conclusions: Concurrent chemoradiation with 5FU-MMC has a statistically significant impact on DFS and OS vs induction + concurrent 5FU-CDDP and borderline significance for CFS, CF and LRF. Therefore, RT+5FU/MMC remains the preferred standard of care. Potential strategies to improve outcomes include treatment intensification and individualized molecular-based treatment. Supported by RTOG grant U10 CA21661 and CCOP grant U10 CA37422 from the National Cancer Institute (NCI). [Table: see text] No significant financial relationships to disclose.
Role of obesity in a randomized placebo-controlled, double-blind trial of difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas.
Authors: Lin B. S. , Zell J. A. , Madson N. , McLaren C. E. , Gerner E. W. , Meyskens F. L. 
Published: February 2017

374 Background: Chemoprevention with difluoromethylornithine (DFMO) plus sulindac markedly reduces risk of recurrence in colorectal adenoma (CRA) patients. Obesity is associated with risk of CRA and colorectal cancer (CRC). This study investigates how obesity influences CRA characteristics at baseline and risk of recurrence after treatment with DFMO plus sulindac vs. placebo. Methods: Our analysis included subjects enrolled in a phase III CRA prevention clinical trial investigating DFMO plus sulindac vs. placebo. Patients were classified by obesity (BMI > 30 kg/m2) status at baseline. Pearson's χ2 statistic or Fisher's exact test and Mann-Whitney U test were used to compare baseline characteristics with regard to obesity status. Log-binomial regression analysis was used to determine the relative risk of metachronous adenoma, adenoma with advanced histology, or multiple adenomas, adjusted for covariates. Results: At baseline, obesity was associated with increased adenoma number (p =0.017), size (p =0.003), advanced histology (p =0.042), high-risk adenomas (p =0.0002), and distal adenomas (p =0.038). Obesity did not modify adenoma recurrence after treatment with DFMO plus sulindac or placebo (p =0.80). Conclusions: Our results provide supporting evidence for the association of obesity with high-risk adenoma features at baseline; however, obesity does not substantially modify CRA risk reduction after treatment with DFMO plus sulindac vs. placebo. [Table: see text] [Table: see text]
Calcium and magnesium infusions for prevention of oxaliplatin-induced peripheral neuropathy.
Authors: Bupathi M. , Mahmud G. , Kovar J. , Wang E. , O'Brien T. E. 
Published: February 2017

387 Background: Oxaliplatin plays an important role in chemotherapy regimens for colorectal and other GI malignancies. Debilitating peripheral neuropathy (PN) often develops with use of this drug. One study (Grothey A et al, ASCO 2009, abst #4025) has shown that pre- and post-oxaliplatin infusions with calcium (Ca) and magnesium (Mg) may reduce this toxicity. To confirm this in an unselected indigent minority population, a retrospective review was performed comparing development of PN in oxaliplatin exposed patients treated with or without Ca/Mg. Methods: Records of patients who received oxaliplatin from 1/2008 to 12/2009 at MetroHealth Medical Center, a large safety net hospital in Cleveland, OH, were reviewed. 47 patients received Ca/Mg + oxaliplatin and 46 oxaliplatin alone. Data collected included age, race, gender, insurance status, performance status, tumor type, stage, concomitant diseases (DM and EtOH), number of cycles and cumulative dose of oxaliplatin. PN was determined using the Common Terminology Criteria of Adverse Events (CTCAE) version 3.0. Patients were followed 6 months after completion of oxaliplatin. Results: Demographic data was similar between the two groups. Colorectal cancer compromised 77% of the treatment group and 85% of control group. Patients who received Ca/Mg had significantly less PN in all three grades (1-3) compared with the control group (grade 1 89.4% vs. 71.7%, grade II 10.6% vs. 19.6%, grade 3 0% vs. 8.7%, respectively). The cumulative dose of oxaliplatin did not differ between the two groups (Ca/Mg median 1,143 range 260-2,169; control median 1,425 range 137-2,635). The combined total grades 2 and 3 in both the treatment and control (10.6% vs. 28.3%, p = 0.038) favored use of Ca/Mg. Conclusions: This small, retrospective study confirms that Ca/Mg infusions reduce the incidence of clinically significant (grade 2/3) PN in pts receiving oxaliplatin. No significant financial relationships to disclose.
Primary appendiceal mucinous adenocarcinoma in two first-degree relatives: Case report and retrospective chart review.
Authors: Racek A. R. , Rabe K. G. , Wick M. J. , Psychogios A. , Lindor N. M. 
Published: February 2017

397 Background: Carcinomas of the appendix are exceedingly rare tumors and have an annual age-adjusted incidence of around 0.4 cases per 100,000. Appendiceal adenocarcinoma accounts for <0.5% of all gastrointestinal neoplasms and, of these, mucinous adenocarcinomas account for the majority. Published accounts of familial instances of primary appendiceal tumors are strikingly rare. Methods: We report two siblings who both developed primary mucinous adenocarcinomas. A genetics evaluation was conducted to determine if there was a recognizable underlying single gene disorder: no DNA mismatch repair defect was evident and no other diagnosis was apparent. A review of appendiceal cancers seen at Mayo Clinic from l997 to the present was conducted to search for additional familial cases. Results: Among 316 cases of primary appendiceal cancer of any histologic type, this sib pair was the only family reporting a second affected family member. Conclusions: The occurrence of appendiceal cancer in siblings may represent a random occurrence. Adenocarcinomas of the most common type of appendiceal cancer and occur at older ages than other histologic subtypes. A strikingly rare predisposition syndrome cannot be ruled out. [Table: see text] No significant financial relationships to disclose.
Effect of surgeon education on lymphadenectomy in colon cancer.
Authors: Young S. E. , Cohn A. L. , Sellers G. , Gomez J. M. , Shapiro H. , Birdsey K. , Spaulding A. 
Published: February 2017

423 Background: The most important determinant of prognosis for localized colon cancer is metastatic lymph node involvement. The American Joint Commission on Cancer and the College of American Pathologists have recommended examination ≥ 12 lymph nodes to ensure adequate staging. We hypothesized that surgeon education would improve the extent of lymphadenectomy in patients being treated for colon cancer. A large community based metropolitan health care system served as a model for testing this hypothesis. Methods: 906 patients comprising AJCC stage I (n=265), stage II (n=304), and stage III (n=337) colon cancers were evaluated. Surgical approach was either open (n=567), laparoscopic (n=310), or unknown (n=29). Lymphadenectomy results obtained from post-operative pathology reports were tracked across four separate time periods: era 1 (1/1/02-1/31/04), era 2 (1/1/05-1/31/06), and era 3 (1/1/07-1/31/07). Results were then compared against a study endpoint measurement of 2008, era four. Results: Upon analysis and comparison of individual era results, a significant improvement in lymphadenectomy (percentage of patients with ≥12 nodes harvested) was noted for all AJCC stages (p-values compare era 4 versus era 1): I (34.2% vs. 59% vs. 65% vs. 69%, P=0.0001), II (62% vs. 76% vs. 90% vs. 91%, P=0.0004), and III (55% vs. 72% vs. 84% vs. 86%, P<0.0001; see table). Surgical approach was not a significant factor. Neither age nor sex was significant. Conclusions: Through physician education, we were able to increase awareness of optimal staging practice for lymphadenectomy in colon cancer. This resulted in significantly improved patient outcomes within a large metropolitan health care system. No significant financial relationships to disclose.
Development of an assay to predict oxaliplatin sensitivity from formalin-fixed, paraffin-embedded (FFPE) colorectal cancer tissues.
Authors: Freedman J. A. , Osada T. , Tsamis K. A. , Morse M. , Clary B. M. , Lyerly H. K. , Nevins J. R. , Clay T. M. , Hsu S. D. 
Published: February 2017

429 Background: Genomic profiling has improved our understanding of the underlying biology of tumors, accuracy of diagnosing disease, predictions of the courses of disease, and ability to determine the therapeutic agents that will be most effective in the treatment of particular tumors. However, in order for assays involving microarray data to be useful in the clinical setting, the ability to generate reliable and consistent data from FFPE tissues is essential. Methods: Cancer cell lines from the NCI-60 collection exhibiting greatest sensitivity or resistance to oxaliplatin were identified. These cells were grown in culture, fixed for 24 hours in formalin, and paraffin-embedded. RNA from the FFPE cells was isolated, amplified, and hybridized to Affymetrix arrays. A Bayesian binary regression analysis was used to generate a predictor of oxaliplatin sensitivity from the gene expression data. Metastatic derived xenografts (MDXs) from resected colorectal tumors were established and treated with oxaliplatin. Samples from tumors prior to treatment were paraffin-embedded and used for RNA extraction, amplification, and hybridization to Affymetrix arrays. The gene expression signature predicting sensitivity to oxaliplatin was then validated with response data from MDXs treated with oxaliplatin. Results: A predictor consisting of 300 genes that could predict sensitivity to oxaliplatin was generated using FFPE samples. Significant correlation was observed between the predicted probability of oxaliplatin sensitivity and the tumor growth inhibition measurement for a given MDX (p=0.0012). Conclusions: Reliable and consistent predictions of oxaliplatin sensitivity can be obtained from gene expression data from FFPE tissues. This method has potential utility in the clinical setting. The ability to predict response to a therapeutic in a FFPE sample has the potential to guide the choice of therapeutics, resulting in an option that could be most effective in treating an individual with metastatic colorectal cancer. No significant financial relationships to disclose.