bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative outcomes for 3D conformal versus intensity modulated radiation therapy for esophageal cancer.
Authors: Freilich Jessica , Chuong Michael , Yue Binglin , Fulp William J. , Abuodeh Yazan Asad , Almhanna Khaldoun , Meredith Kenneth , Karl Richard C. , Hoffe Sarah , Shridhar Ravi 
Published: February 2017

76 Background: Emerging data suggests a benefit for using intensity modulated radiation therapy (IMRT) for the management of esophageal cancer. Methods: We retrospectively reviewed patients treated at our institution who received definitive or preoperative chemoradiation with either IMRT or 3D conformal radiation therapy (3DCRT) between October 2000 and January 2012. Kaplan Meier analysis and the Cox proportional hazard model were used to evaluate survival outcomes. Results: We evaluated a total of 232 patients (138 IMRT, 94 3DCRT) who received a median dose of 50.4 Gy (range, 44-64.8) to gross disease. Median follow up for all patients, IMRT patients alone, and 3DCRT patients alone was 18.5 (range, 2.5-124.2), 16.5 (range, 3-59), and 25.9 months (range, 2.5-124.2), respectively. We observed no significant difference based on radiation technique (3DCRT vs. IMRT) with respect to median overall survival (OS) (29 vs. 32 months; p=0.78) or median relapse free survival (RFS) (20 vs. 25 months; p=0.74). On multivariable analysis (MVA), not undergoing surgical resection resulted in worse OS (HR 2.255; p <0.0001) and RFS (HR 1.893; p<0.0001). Superior OS was associated on MVA with stage I/II disease (HR 0.523; p=0.010) and tumor length ≤5 cm (HR 0.567; p=0.006). Improved RFS on MVA was associated with stage I/II disease (HR 0.663; p=0.070), tumor length ≤5 cm (HR 0.611; p=0.011), adenocarcinoma histology (HR 0.532; p=0.055), and 3DCRT(HR 0.524; p=0.002). IMRT was also associated on univariate analysis with a significant decrease in acute weight loss (mean 6%+4.3% vs 9%+7.4%, p=0.0001) and on MVA with a decrease in objective grade ≥ 3 toxicity, defined as any hospitalization, feeding tube, or >20% weight loss (OR 0.51; p=0.050). Conclusions: Our data suggest that while IMRT-based chemoradiation for esophageal cancer does not impact survival there was significantly less toxicity. In the IMRT group there was significant decrease in weight loss and grade ≥3 toxicity compared to 3DCRT.
Reporting of subgroup analyses (SGA) in phase III randomized trials in gastrointestinal (GI) cancer.
Authors: Barton Sarah Rachel , Chau Ian , Peckitt Clare , Sclafani Francesco , Cunningham David 
Published: February 2017

78 Background: Correct interpretation of SGA is important as it influences selection of therapeutic interventions for patient subsets. We aimed to evaluate the association of prospectively determined study characteristics with reporting of SGA and claims of subgroup effects in GI cancer trials. Methods: We performed a systematic literature review and extracted data from all articles meeting the following criteria: published 01/01/2003-01/09/2012 in peer-reviewed journal; reporting results of phase III randomised controlled trial; n≥150; testing investigational medicinal product in GI cancer. The primary aim was to compare reporting of SGA between industry and nonindustry sponsored trials. Results: 145 trials were identified. SGA were reported in 100 (69%). A significantly larger median number of SGA were reported in industry than in non-industry sponsored trials (6 vs 2, p=0.004). In the 52 trials claiming subgroup effects, significant test of interaction was evident in only 25%, with no difference between industry and non-industry trials (Table). There was an association between larger number of trial subjects and more SGA reported (p<0.001). Trials of targeted therapy compared to cytotoxic (median 6 vs 2, p=0.004) and trials with significant primary endpoint (median 6 vs 2, p=0.006) reported more SGA. Industry sponsored trials with a significant primary endpoint reported more SGA (median 8) than others (p<0.001). Conclusions: Industry sponsored trials with positive result and trials of targeted therapy appear to report SGA more frequently. Since only quarter of trials claiming subgroup effects had evidence of significant test of interaction, circumspection should be adopted when using SGA as the basis for variance in GI cancer treatment. Conference abstracts may contain more SGA, and these will be incorporated into further analyses. [Table: see text]
Association of low serum levels of transforming growth factor β1 (TGF-β1) and high levels of vascular endothelial growth factor-A (VEGF-A) following neoadjuvant chemoradiotherapy with poor outcome in esophageal cancer patients receiving combined modality therapy: A preliminary analysis using proximity ligation assay.
Authors: Graber Madeline S , Cheng Jason C. , Hsu Feng-Ming , Koong Albert 
Published: February 2017

80 Background: Currently, serum biomarkers do not influence the treatment of esophageal cancer. The purpose of this project is to investigate, using the proximity ligation assay (PLA), serum biomarkers that predict treatment response and survival outcome for patients with locally advanced esophageal cancer (LAEC) undergoing neoadjuvant concurrent chemoradiotherapy (CCRT) followed by radical esophagectomy. Methods: From 2004 to 2011, 79 patients with LAEC receiving CCRT of taxane-based chemotherapy and 40 Gy followed by curative surgery were enrolled in this study. Serum samples were collected before and within one month after CCRT. Fifteen biomarkers (Axl, BMP2/4, EGFR, FAM84B, Gas6, Her2, IGFBP3, MMP1, MMP13, OPN, PDGFR-α, Periostin, SPARC, TGF-β1, VEGF-A) were analyzed using PLA. Pathological responses were classified into complete response (CR), microscopic residual (MicroR), or macroscopic residual (MacroR). Associations between serum level of each biomarker and pathological response, disease-free survival (DFS), and overall survival (OS) were evaluated by ANOVA and Log-rank tests. Results: Of 79 patients, 30 had CR (38%), 37 had MicroR (47%) and 12 had MacroR (15%). With a median follow-up of 54.5 months, the median OS and DFS were 34 and 43 months, respectively. Among evaluated biomarkers, TGF-β1 was the most significant one associated with pathological response (p=0.009, two-way ANOVA), with higher post-CCRT TGF-β1 levels predicting better response (p=0.035, one-way ANOVA). Patients with higher post-CCRT TGF-β1 levels (≥3rd quartile) had significantly better DFS (median not reached vs. 27 months, p=0.03). Patients with both lower levels of post-CCRT TGF-β1 and higher levels of VEGF-A had significantly worse DFS (13 months, p=0.001) and OS (18 months, p=0.035). Conclusions: Post-CCRT serum TGF-β1 and VEGF-A levels by PLA may be used to predict pathological response and survival outcome for esophageal cancer patients receiving combined modality therapy.
The impact of race on gastric cancer outcomes in the United States.
Authors: Powers Benjamin Daniel , Daly Maureen Patricia , Davey Adam , Taghavi Sharven , Jayarajan Senthil N. , Willis Alliric Isaac 
Published: February 2017

83 Background: Disparities in gastric cancer outcomes are well-documented. We evaluate the association of race with gastric cancer outcomes using a diverse database of patients in the U.S. Methods: SEER was queried for gastric adenocarcinoma cases from 2004-2008, excluding cardia. Logistic (LR) and Cox regressions were used for analyses. Results: 9,440 cases were analyzed: 4,134 (43.8%) Whites (W), 2,015 (21.3%) Asian-American Pacific Islanders (AP), 1,826 (19.3%) Hispanics (H), and 1,465 (15.5%) Blacks (B). Presentation: Average age was 70.1. B, H, and AP were more likely than W to present younger. AP were more likely and H less likely than W to present at a lower stage. B were more likely to have a lower grade. No differences in gender were seen. Treatment: Compared to W, AP were more likely to have surgery. AP, H, and B were more likely to receive radiation (XRT). AP and H had increased odds of ≥15 lymph nodes examined (LNE). Survival: AP and H had improved but B had worse survival compared to W when stratified by receipt of surgery, XRT, and stage and adjusted for age, gender, LNE, anatomic site, and grade. Conclusions: AP were more likely to present with lower stage, have surgery, XRT, ≥15 LNE, and highly significantly better survival than W. H were more likely to present younger but with higher stage, have ≥15 LNE, XRT, and better survival. For B there were no differences in stage or receipt of surgery, though there were increased odds of XRT but had worse survival. These racial disparities in gastric cancer suggest potential differences in tumor or host biology and quality of treatment that impact outcomes and merit further study. [Table: see text]
A phase I dose-finding study of everolimus in combination with capecitabine and oxaliplatin (XELOX) as the first-line chemotherapy for patients with advanced gastric cancer.
Authors: Park Inkeun , Ryu Min-Hee , Ryoo Baek-Yeol , Kang Myoung Joo , Lee Changsuk , Park Young Soo , Kang Yoon-Koo 
Published: February 2017

86 Background: The purpose of this phase I study is to determine the recommended dose (RD) of everolimus (E), an mTOR inhibitor, in combination with capecitabine (XEL) and oxaliplatin (OX) and to explore feasibility of EXELOX at the RD in advanced gastric cancer (AGC). Methods: The standard 3+3 method was used to determine the RD of 3-weekly EXELOX during the first cycle. The doses of each drug [E (mg/day, D1-D21)/XEL (mg/m2/day, D1-D14)/OX (mg/m2, D1)] were as follows: level 1, 7.5/1600/100; level 2A, 7.5/1,600/130; level 2B, 7.5/2,000/100; level 3A, 10/1,600/130; level 3B, 10/2,000/100; level 4, 7.5/2,000/130. Results: During the first cycle of chemotherapy, no dose limiting toxicity (DLT) was noted in each cohort of 3 patients (pts) at dose levels 1-3A. At dose level 3B, 1 DLT (delay of the next cycle over 3 weeks because of Gr2 thrombocytopenia and Gr2 AST) was observed out of 6 pts. At dose level 4, DLTs (Gr3 fatigue and Gr4 thrombocytopenia) were found in 2 out of 3 pts. However, with frequent dose delay or reduction in subsequent cycles, the actual dose intensity of XELOX during the first 3 cycles was not higher at dose levels 2 or 3 than at dose level 1. Accordingly, dose level 1 was finally considered more suitable to maintain the actual dose intensity over chemotherapy cycles. At dose level 1, with no DLT during the first 3 cycles in 3 more pts accrued to confirm the safety, 12 additional pts were enrolled in the extension cohort to explore feasibility of EXELOX in the aspect of efficacy. Among 16 patients with measurable disease at dose level 1, 8 (50%) pts achieved a confirmed PR, 7 (44%) had SD, and 1 (6%) showed PD as a best response. With a median follow-up period of 12 months (range 4.9–12.8 months), the median progression-free survival and overall survival were 5.5 and 8.1 months, respectively at dose level 1. Conclusions: In this study, the doses of XEL (1,600 mg/m2/day), OX (100 mg/m2), and E (7.5 mg/day) were recommended with good tolerability for the 3 weekly EXELOX combination as the 1st line chemotherapy for AGC. The efficacy of this combination needs to be evaluated in future trials. Clinical trial information: NCT01049620.
Does radiation therapy increase late cardiac death in patients with esophageal cancer?
Authors: Lin Chi , Denniston Kyle A. 
Published: February 2017

90 Background: The objective of this study was to evaluate the effect of radiation therapy (RT) on late cardiac death in patients with esophageal cancer. Methods: A total of 35,618 patients diagnosed with esophageal squamous cell carcinoma (SCC) or adenocarcinoma (ADE) between 1973 and 2008 were identified from the SEER database. After excluding records with missing data, 24983 patients remained. Patients who survived ≥ 5 years (2075) were identified for this analysis. Examined risk factors for cardiac death include age (≤55/56-65/66-75/>75), gender, race (white/non-white), stage (local/regional/distant), histology (SCC/ADE), esophageal subsite (<18cm/18-24cm/25-32cm/33-40cm), diagnosis year (1973-1983/1984-1993/1994-2003), and treatment with surgery or RT. Time to cardiac death was evaluated using the Kaplan-Meier method. A multivariate logistic regression model with backward elimination and the Cox Proportional Hazards model were used to evaluate risk factors for cardiac death. Results: Patients who received RT tended to be younger, white, diagnosed more recently, have more advanced disease, SCC histology and not undergo surgery. RT group had a higher risk of cardiac death than no-RT group (Log-Rank p < 0.0001). Median time to cardiac death in RT group was 251 months (95% CI 223-367) and was not reached in no-RT group. The probability of cardiac death increased with age and decreased with diagnosis year. This trend was more pronounced in RT group. Multivariate analysis found RT to be associated with higher probability of cardiac death (OR 1.45, 95% CI 1.10-1.93), after adjusting for age and diagnosis year. Gender, race, histology, stage, esophageal subsite and surgery status were not associated with cardiac death. After adjusting for age, Cox model showed that patients who received RT were more likely to die of cardiac causes than those who did not receive RT (HR 1.91, 95% CI 1.47-2.47). Diagnosis year was not a risk factor in the Cox model. Conclusions: Patients with esophageal cancer who received RT and survived ≥ 5 years had a higher risk of cardiac death than those who did not receive RT. Further study of cardiac outcome in long term survivors of esophageal cancer treated with RT, and accounting for comorbidity, is warranted.
Phase II trial of sorafenib in esophageal (E) and gastroesophageal junction (GEJ) cancer: Response and prolonged stable disease observed in adenocarcinoma.
Authors: Ku Geoffrey Y. , Janjigian Yelena Yuriy , Shah Manish A. , Herrera Jessica , Tang Laura H. , Fuqua Louis , Capanu Marinela , Ilson David 
Published: February 2017

91 Background: Sorafenib is a tyrosine kinase inhibitor targeting VEGFr, PDGFr, Raf and other pathways. Encouraging response and survival were observed in a phase II trial of sorafenib with chemotherapy in GE cancer (J Clin Oncol 27:2947;2010). We performed a phase II trial of single-agent sorafenib with the primary endpoint of progression-free survival (PFS). Secondary endpoints include response and toxicity. Methods: Patients (Pts) with measurable metastatic E and GEJ cancer with ≤3 prior chemotherapy regimens were treated with sorafenib 400 mg BID. CT scans were performed monthly for the first 2 months, then every 2 months. Results: Thirty-five patients have been accrued, with 34 evaluable; median age 62, 31 male, 4 female, median KPS 80%, E 25, GEJ 10, adenocarcinoma (AC) 30 squamous 5, median no. of prior therapies 2. Of 31 response-evaluable Pts, 1 (3%) ongoing complete response was noted (34+ months) in a Pt with E AC with biopsy-proven lymph node recurrence after chemoradiation and surgery; 23 Pts (74%) had stable disease. Median PFS is 3.7 months (95% CI 1.9 to 4 months), with median overall survival 8.9 months (95% CI 6.9 to 11.6 months). Four patients remain on treatment. Significant grade 3 toxicities included hand foot reaction (3 Pts), rash (1 Pt), dehydration (3 Pts) and fatigue (2 Pts). Twenty-seven of 33 tumors (82%) tested positive for phospho-ERK by immunohistochemistry. Conclusions: Encouraging activity in terms of PFS has been noted in this heavily pre-treated population. Updated data will be presented. Supported by a grant from Bayer. Clinical trial information: NCT00917462.
Patterns of locoregional relapses for patients with esophageal cancer for whom exclusive chemoradiotherapy failed: A plea for dose escalation and elective nodal irradiation.
Authors: Chevalier Cedric , Vulquin Noemie , Gauthier Mélanie , Petitfils Aurelie , Martin Etienne , Truc Gilles , Peignaux-Casasnovas Karine , Khoury Cedric , Wiazzane Nadia , Maingon Philippe , Crehange Gilles 
Published: February 2017

99 Background: Nearly half of the patients (pts) with an esophageal cancer (EC) have a locoregional failure (LRF) after exclusive chemoradiation (eCRT). eCRT delivering 50Gy remains the standard of care for non operable pts. We aim to evaluate the patterns of LRF with respect to planned dose and/or the incidental (unplanned) dose that covered LRF. Methods: Twenty-two pts with EC who failed locally and/or regionally in their follow-up were exclusively reviewed. All the pts have been initially treated (t0) in a curative intent with eCRT. Co-image registration of CT or PET-CT at time of failure and planning CT at t0 was used for image fusion. Each nodal failure (Nf) and each local failure of the primary tumor (Lf) has been outlined, as well as each nodal station (NS) including Nf according to the RTOG classification. Dosimetric parameters in relation with Lf, Nf and involved NS were derived from the initial dosimetric plan. Results: All the patients underwent eCRT including a 5-FU based chemotherapy regimen. Eighteen patients were treated with elective nodal irradiation (ENI) whereas 4 pts did not. The median dose delivered was 50Gy [50Gy-64Gy]. In the follow-up period, 14 pts were in complete response, 3 pts in partial response, 4 pts had a progressive disease (1pt unknown). The median delay between the start of radiotherapy and LRF was 14.3 months [4.27-48.46]. 13 pts had a Lf (included in “planned-dose”), 9 pts had a Nf, 2 pts had a Lf with Nf and 7 pts had a concomittant distant failure. Among pts with Nf, 8 failures were in-field whereas 3 pts had an out-field relapse. Re-calculated doses for NS delineated on the CT performed at t0 were significantly less important than the planned dose (see Table). Conclusions: Our results suggest that an inadequate dose to both the primary tumor and NS could explain high LRF rates observed in EC. A French randomized phase III trial (NCT 01348217) is currently testing a higher dose to the primary tumor and/or ENI with IMRT in an attempt to improve locoregional control. [Table: see text]
Ex vivo prostate cancer explant organ culture model system for targeted drug development in prostate cancer
Authors: Gupta Shilpa , Gu Lei , Liao Zhiyong , McCue Peter , Trabulsi Edouard John , Nevalainen Marja T. 
Published: February 2017

110 Background: Effective drug development does not always occur successfully in prostate cancer despite discovery of pathways and targeted agents due to lack of pre-clinical models that effectively mimic prostate cancer in humans. We optimized a novel Ex vivo organ-culture model system using clinical human prostate cancers to test novel therapeutic agents targeting the Jak2/Stat5a/b pathway in prostate cancer; this pre-clinical model may be useful to test novel drugs in prostate cancer for target validation and efficacy. Methods: Organ explant cultures of prostate cancers from 16 patients undergoing radical prostatectomy were performed within 2 hours of surgery, 1-2 mm fresh tissue explants were cultured in a medium containing different doses of pharmacologic inhibitor of Stat5a/b (IST5-002) or a small molecule Jak2 inhibitor with appropriate controls and treated with the drug daily for 7 days. Explants were fixed and analyzed for viability by hematoxylin-eosin staining and “in situ DNA end-labeling” assays, Stat5 activation was analyzed by immunohistochemistry for phosphorylated Stat5a/b. Results: Morphology of prostate cancer was well maintained and dose-dependent tumor responsesoccurred with the Stat5a/b and Jak2 inhibitors. The minimum effective dose of each drug was 25 micromoles and considerable effects on morphology and apoptosis were seen at 50 micromoles. Conclusions: Inhibition of the /Stat5a/b pathway showed promising preclinical activity in prostate cancer as demonstrated by our 3D-ex vivo explant organ culture model system using clinical human prostate cancers, corroborating the data from prostate cancer cell lines and xenograft prostate tumors. This model system may also serve as an effective pre-clinical tool to explore new targets and analyze the effects of different targeted therapies in prostate cancer. Finally, since this uses Ex vivo prostate cancer explants from individual prostate cancer patients, once could test different targeted agents in parallel and based on the efficacy of individual drugs, select patients who would best respond to a particular drug, thus providing an effective personalized medicine approach.
A randomized phase II trial of dexamethasone versus prednisolone as secondary hormonal therapy in CRPC.
Authors: Venkitaraman Ramachandran , Thomas Karen , Murthy Vedang , Woode-Amissah Ruth , Dearnaley David Paul , Horwich Alan , Huddart Robert Anthony , De Bono Johann Sebastian , Parker Chris 
Published: February 2017

123 Background: Dexamethasone and prednisolone are glucocorticosteroids used as second line hormonal treatment for castration refractory prostate cancer (CRPC). The biochemical response rates in cohort studies suggest that dexamethasone may be the more active agent. We conducted an open label, randomised phase II trial of dexamethasone versus prednisolone. Methods: Patients with castration resistant prostate cancer with progressive disease on androgen deprivation therapy were eligible. They were randomized to receive either prednisolone 10mg daily or dexamethasone 0.5mg daily. The main endpoint was confirmed PSA response rate according to the PSA Working Group 2 criteria. Patients with PSA progression on prednisolone crossed over to dexamethasone. Secondary endpoints included time to PSA progression, radiologic response rate using RECIST criteria, and safety. Results: Seventy-five patients were randomized. Confirmed PSA response was achieved in 12/39 patients (31%) on dexamethasone compared to 6/36 (17%) on prednisolone (p = 0.153). Median time to PSA progression was 9.7 months on dexamethasone compared to 5.1 months on prednisolone (HR 1.57, 95% CI 0.90 -2.75). In 43 patients with measurable disease, the response rate by RECIST criteria was 15% and 6% for dexamethasone and prednisolone, respectively (p = 0.606). Clinically significant toxicities were rare. Of 23 patients who crossed over at progression on prednisolone to dexamethasone, 19 patients were evaluable for PSA response. Seven of the 19 patients (37%) had a confirmed PSA response to dexamethasone after progression on prednisolone. Conclusions: The data are consistent with the hypothesis that dexamethasone is more active than prednisolone in the treatment of CRPC. In the absence of definitive, larger trials, dexamethasone should be used in preference to prednisolone in this setting. Clinical trial information: 2005-006018-16.