bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of preoperative docetaxel, cisplatin, and capecitabine in patients with gastric carcinoma.
Authors: Voon Pei-Jye , Soe Mu-Yar , Zee Ying Kiat , Chuah Benjamin , Lim Robert S. C. , Shabbir Asim , So Jimmy , Yong Wei-Peng 
Published: February 2017

89 Background: Perioperative chemotherapy has been shown to improve outcomes among patients with locally advanced gastric adenocarcinoma. As docetaxel (D), cisplatin (C), and capecitabine (X) are active agents in gastric adenocarcinoma, we conducted a phase II trial to assess the efficacy and tolerability of preoperative DCX in patients with gastric adenocarcinoma. Methods: We enrolled patients with locally advanced gastric adenocarcinoma (clinical T3/4 or N positive) to preoperative DCX repeated every 21 days for three cycles, followed by surgery. The first cohort of 10 patients received docetaxel 35 mg/m2, cisplatin 35mg/m2 on days 1 and 8, with capecitabine 750 mg/m2 twice daily from day 1 to day 14. A subsequent cohort of another 11 patients had dose modifications for docetaxel and cisplatin, both to 30mg/ m2 on days 1 and 8. Results: Twenty-one patients were recruited. Median age was 61 years. Seventy-one percent of patients completed a total of 3 cycles of planned chemotherapy. Fourteen patients have successfully undergone surgery. R0 resection rate was 88%. Pathological complete response (pCR) and near complete response (pnCR) were both 17%. Preoperative radiological assessment showed a partial response rate of 65% after 2 cycles of treatment. Good pathological response (pCR and pnCR) was associated with better event-free survival (26 months vs 12 months, p=0.031). Common grade 3/4 toxicities were diarrhea (38%), neutropenia (30%), stomatitis (14%) and hypokalemia (14%). However, the diarrhea rate was reduced to 15% with dose modifications as mentioned above after 50% of the first cohort of 10 patients developed grade 3/4 diarrhea during the first cycle of chemotherapy. Febrile neutropenia rate was 14%. There was one treatment related death before surgery but no postoperative mortality. Conclusions: Preoperative DCX is highly active with modest toxicity in locally advanced gastric adenocarcinoma. DCX represents an attractive alternative regimen without the need for protracted infusional drug in perioperative chemotherapy for patients with locally advanced gastric adenocarcinoma. Good pathological response is associated with better outcome.
Cetuximab plus chemotherapy in patients with liver-limited or non-liver-limited KRAS wild-type colorectal metastases: A pooled analysis of the CRYSTAL and OPUS studies.
Authors: Kohne Claus-Henning , Bokemeyer Carsten , Sartorius Ute , Schlichting Michael , Rougier Philippe , Van Cutsem Eric 
Published: February 2017

96 Background: In the CRYSTAL and OPUS studies, adding cetuximab (cet) to first-line chemotherapy (CT) improved clinical benefit in patients (pts) with KRAS wild-type (wt) metastatic colorectal cancer. In a pooled analysis of these trials the benefit of treatment according to whether pts had liver-limited disease (LLD) or non-LLD was investigated. Methods: Cox‘s proportional hazards model for overall survival (OS) and progression-free survival (PFS) or logistic regression model for objective response rates (ORR) and R0 resection were used on individual pt data, stratified by study. Likelihood ratio tests were used to statistically explore interactions. Results: Adding cet to CT significantly improved PFS and ORR in LLD pts, and OS, PFS and ORR in non-LLD pts ( table ), and increased R0 resection rates: LLD 11.8% vs 5.3%, odds ratio=2.38, p=0.11 and non-LLD, 3.3% vs 1.7%, odds ratio=1.97, p=0.19. No treatment-by-study interactions were noted. Treatment effects did not vary significantly by LLD status (PFS, p=0.60, OS, p=0.68, ORR p=0.074). However LLD vs non-LLD pts had improved outcome in each treatment arm: PFS, CT HR=0.74, p=0.091; CT + cet HR=0.66, p=0.031; OS, CT HR=0.70, p=0.009; CT + cet HR=0.74, p=0.039; ORR, CT odds ratio=1.20, p=0.47, CT + cet odds ratio=2.32, p=0.002; R0 resection, CT odds ratio=3.15, p=0.050, CT + cet odds ratio=3.82, p=0.0018. Conclusions: The OS benefit from adding cet to CT is mainly seen in pts with non-LLD, thus strengthening the value of cet in palliative treatment. LLD status appears to be predictive for response in pts receiving CT + cet, facilitating potential resection. A larger number of pts (with R0 resection and longer follow-up) may be needed to confirm an OS benefit from CT + cet in LLD pts. [Table: see text]
Results of a comparison between European countries for esophagectomy and gastrectomy: Initiative for a European upper GI audit (EURECCA Upper GI).
Authors: Van De Velde Cornelis J. H. , Dikken Johan L. , Wouters Michel W. , Putter Hein , Lemmens Valery E. P. , Verheij Marcel , Cats Annemieke , Johansson Jan , Jensen Lone S. , Allum William H. , Coupland Victoria , van Sandick Johanna W. 
Published: February 2017

98 Background: In Europe, several countries have implemented national audit programs to reduce variation in outcomes and improve care for esophageal and gastric cancer. These audits provide insight in national variations, but currently no international comparisons can be made. Purposes of the current study were to compare patterns of care and outcomes in several European countries, and to evaluate the effect of hospital volume on outcomes for esophagectomy and gastrectomy. Methods: Data were obtained from national cancer registries or audits in the Netherlands, Sweden, Denmark, and the United Kingdom. Differences in postoperative 30-day mortality and 2-year survival were adjusted for available case-mix variables and separately analyzed for esophagectomy and gastrectomy, using generalized estimated equations and Cox regression. In the current study, high-volume hospitals were defined as hospitals with an annual volume of > 20. Results: From 2004-2009, 10,854 esophagectomies and 9,010 gastrectomies were performed in the participating countries. Availability of case-mix variables varied between countries, and a limited number of variables could be used in the international comparison. On univariate analysis, 30-day mortality and 2 year survival differed significantly between participating countries, but on multivariate analysis, no significant differences were found. The percentage of resections performed in high-volume hospitals varied considerably between countries (esophagectomy: 20% to 94%, gastrectomy: 0% to 59%). Increasing annual hospital volume was associated with lower 30-day mortality after esophagectomy (P < 0.001) and gastrectomy (P = 0.025), and with improved 2-year survival after esophagectomy (P = 0.004), but not after gastrectomy. Conclusions: This study provides an initial step towards a European Upper GI Cancer Audit. However, with the available data only limited case-mix adjustments could be made. Future steps would include synchronization of registered variables and the use of uniform variable definitions. Increasing annual hospital volume is associated with improved short-term outcomes of upper GI cancer surgery.
Value of multimodality MRI and MR-guided biopsy at inclusion in an active surveillance protocol for prostate cancer.
Authors: Somford Diederik Meindert , Hoeks Caroline M. , van den Bergh Roderick C. , Vergunst Henk , van Oort Inge M , Smits Geert A. , Oddens Jorg R. , Hulsbergen - van de Kaa Christina A , Bangma Chris H. , Witjes J. Alfred , Barentsz Jelle O. 
Published: February 2017

105 Background: To prevent overtreatment of insignificant and/or low-risk prostate carcinoma in the PSA screening era, active surveillance is emerging as a treatment strategy for selected patients. In our series we aim to establish whether MRI could aid in correct risk assessment for these patients within the framework of the Prostate Cancer Research International Active Surveillance (PRIAS) study. Methods: We included patients in our protocol based on contemporary criteria for active surveillance: - Diagnosis of prostate cancer by TRUS-guided biopsy. - PSA ≤10 ng/mL, PSA density <0.2 ng/mL/mL - Clinical stage ≤ T2 - Gleason score (GS) ≤3+3=6 - ≤ 2 biopsy cores with cancer All patients underwent multimodality MRI of the prostate, including T2-weighted, diffusion-weighted and dynamic contrast-enhanced MR sequences. When a tumor-suspicious region (TSR) could be identified a targeted MR-guided biopsy (MRGB) was performed to obtain pathology. Patients were referred for definitive treatment in case of GS > 3+3=6 upon MRGB or T3 stage at MRI. Results: In 48 of 49 included patients at least one TSR was identified, with a median of 2 TSRs (range1-4) per patient. MRGB was obtained from every TSR, with a median of 4 MRGBs taken per patient. Five patients had a GS >3+3=6 upon MRGB and were excluded. Three patients were excluded due to suspicion of T3 stage on MRI. Five patient were excluded upon physician’s discretion due to multifocal prostate cancer upon MRGB. Combined multimodality MRI/MRGB in our active surveillance cohort thus excluded 27% (13/49) of patients who were incorrectly stratified as low-risk prostate carcinoma by contemporary criteria. Conclusions: Application of multimodality MRI and MRGB in an active surveillance protocol improves risk stratification, adding onto contemporary PSA and TRUS-guided biopsy criteria for low-risk prostate cancer. This approach might increase safety and reliability of active surveillance for prostate cancer and deserves ongoing prospective evaluation.
Comparing long-term toxicity between external beam radiotherapy modalities: A SEER/Medicare database study.
Authors: Reddy Chandana A. , Ciezki Jay P. , Abdel-Wahab May , Angermeier Kenneth , Ulchaker James , Stephans Kevin L. , Tendulkar Rahul D. , Altman Andrew , Chehade Nabil , Klein Eric A. 
Published: February 2017

118 Background: The use of intensity modulated radiotherapy (IMRT) for the treatment of prostate cancer (CaP) has been widely promoted due to the hypothesized benefit of low late toxicity. Methods: The SEER-Medicare database was queried for CaP patients treated with external beam radiotherapy (EBRT), 1991-2007. CPT billing codes were used to identify patients treated with IMRT or standard EBRT (sEBRT), which was comprised of conformal radiotherapy or a four-field technique. Patients without a treatment billing code were excluded from the analysis. Information on dose is unavailable. CPT codes were also used to identify procedures associated with gastrointestinal (GI) or genitourinary (GU) toxicity related treatments. Cumulative incidence rates for GI and GU toxicity were calculated with death treated as a competing event. Results: A total of 137,427 patients who were 65 years or older at the time of CaP diagnosis and who had CaP as their only cancer diagnosis were retrieved from the SEER-Medicare database: 60,806 were treated with EBRT and a treatment billing code was identified for 35,388 patients. No patient received combined therapy. Seventeen percent of patients received IMRT. The median follow-up for patients receiving IMRT is 40 months (mo) (range 2-157) vs 77 mo (range 0-203) for patients receiving sEBRT. Overall, 3,699 (10%) patients experienced a toxicity requiring an intervention. The five year rate of GI The gastrointestinal (GI) and genitourinary (GU) toxicity comparisons are listed in the table. For both endpoints, rate of toxicity at five years was higher for the IMRT group. The most common GU toxicity for both groups was dilation of a urethral stricture (3.8% of all sEBRT patients vs 3.4 of all IMRT patients). Cauterization of rectal bleeding was the most common GI toxicity (2.4% of all sEBRT patients vs 1.6 of all IMRT patients). Conclusions: While the rates of GI toxicity between IMRT and sEBRT are comparable, of concern is the higher rate of GU toxicity for the IMRT patients despite this group having a shorter follow up than the sEBRT group. [Table: see text]
Role of homeobox pathway in prostate carcinogenesis.
Authors: Chen James Lin , Otto Kristen , Vander Griend Donald 
Published: February 2017

126 Background: Identifying aberrant activity of developmental pathways in prostate cancer provides therapeutic opportunities. To this end, despite a shared embryonic origin and similarities to prostate cancer in histology and androgen dependence, seminal vesicle cancer is exceptionally rare. Genomic pathway analyses of their critical developmental differences may reveal uncharacterized oncogenic pathways. Previous attempts to do so have used whole tissue preparations. We hypothesized that careful gene profiling of pure primary epithelial cultures from normal prostate and seminal vesicles would reduce confounding noise during analysis and provide more robust pathway prioritization. Methods: Paired normal prostate and seminal vesicle epithelium cultures were created from three de-identified patients. Derived gene expression profiles were grouped into cancer biomodules using a protein-protein network algorithm to analyze their relationship to known oncogenes. Each resultant biomodule was assayed for its prognostic ability in independent Kaplan-Meier analyses of prostate cancer patients for time to recurrence and overall survival. Protein products from prioritized biomodule genes were then evaluated in vitro. Results: Gene expression profiling and protein network prioritization resulted in three cancer biomodules. Survival analysis revealed that the embryonic developmental biomodule centered on homeobox genes Meis1, Meis2 and Pbx1 to have clinical import. This homeobox biomodule detected a survival difference in a set of active surveillance patients (n=172, p=0.05) and identified men who were more likely to recur biochemically post-prostatectomy (n=78, p=0.02). We analyzed in vitro protein expression of Meis1, Meis2, Pbx1 and confirmed decreased gene expression in independent datasets of prostate cancer versus normal tissue. Conclusions: The Meis1/Meis2/Pbx1 biomodule may explain key differences in seminal vesicle and normal prostate epithelium development. In contrast to other cancers, Meis1, Meis2, and Pbx1 may play a tumor suppressor role in prostate cancer. Thus deregulation of this biomodule may be critical in prostate cancer oncogenesis.
Overcoming chemotherapy resistance in patients (pts) with chemotherapy-failure, castration-resistant prostate cancer (CRPC) with sorafenib.
Authors: Nabhan Chadi , Cygan Peter Hubert , Meyer Andrew , Tolzien Kathy , Galvez Angel G. , Lestingi Timothy M. , Bitran Jacob D. 
Published: February 2017

127 Background: SOR is an oral multi kinase inhibitor that promotes apoptosis through downstream pathways that can be deregulated in CRPC leading to chemotherapy resistance. We hypothesized that SOR Could overcome chemotherapy resistance in non-responders or in those who progress shortly after stopping chemotherapy. Methods: Eligible pts were those who progressed while receiving chemotherapy [docetaxel (D) or mitoxantrone (M)] or within 12 weeks from stopping it. Pts were then continued or resumed on their last chemotherapy with the addition of SOR at 400 mg PO BID. Pts were allowed a maximum of 6 cycles of chemotherapy +SOR followed by SOR as monotherapy until progression. Primary end point: Safety of SOR+ chemotherapy. Secondary end points: Toxicity, time to progression (TTP). And responses (biochemical and radiographic) Results: Twenty-two pts were enrolled; 21 evaluable (73% Gleason ≥ 7). Median age was 68 (59-83). Median PSA was 142 ng/dl (13.6-9,584). Median time from last chemotherapy to SOR was 4 weeks. Visceral and bone disease was present in 64%. D was given in 16 pts while M in 6. Ten pts (45%) showed biochemical response (18% with >50% PSA decline). Despite progression before being on study, 16 pts (76%) achieved SD after starting SOR for a median duration of 6 months (4-12). The combination of SOR with either chemotherapy agent proved safe. Main grade 3/4 non-hematologic toxicities: Fatigue 7 (32%), 4 (18%) hand/foot syndrome, hypocalcemia and hyperglycemia in 2 pts (9%) each. Grade 3/4 leukopenia was seen in 7 (31%), neutropenia in 6 (27%), and thrombocytopenia in 2 (9%). Dose reduction of SOR occurred at least once in 15 pts (68%). Major reasons are hand/foot syndrome (22%), fatigue (22%), rash (13%), and neutropenia (9%). With a median follow-up of 19 months (3-46), 5 pts (23%) remain alive for a median OS of 8 months. TTP by PSA was 3 months (2-6) and TTP by imaging and/or clinically was 6 months (2-12). Median number of treatment cycles given was 6 (1-10). Conclusions: SOR can safely be combined with chemotherapy. SOR overcomes chemotherapy-resistance and shows biochemical and radiographic stability in this refractory pt population.
Effect of neoadjuvant docetaxel treatment for locally advanced prostate cancer on miRNA expression: A pilot study.
Authors: Falzarano Sara Moscovita , Zhou Ming , Carver Paula , Klein Eric A. , Dreicer Robert , Magi-Galluzzi Cristina 
Published: February 2017

139 Background: Taxanes are microtubule-stabilizing drugs used investigationally in adjuvant and neoadjuvant settings of prostate cancer (PCA) treatment in an attempt to improve systemic control of high risk disease. Understanding mechanism of response to taxanes is an essential step in developing novel combination therapies to improve PCA response rates. MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression by binding target messenger RNAs and inhibiting their stability and/or translation. In cancer miRNAs can act as oncogenes and/or tumor suppressor genes. The objective of our study was to identify miRNAs that are affected by neoadjuvant docetaxel in high-risk PCA. Methods: Whole cell RNA was extracted from formalin-fixed paraffin-embedded (FFPE) radical prostatectomy specimens from 8 patients with high grade PCA treated with neoadjuvant docetaxel, 8 high grade untreated PCA and their corresponding untreated non-neoplastic tissue. Tumors were matched by Gleason score, patient age and year of surgery. The expression of 88 cancer-associated miRNAs was then quantified using a PCR-based miRNA microarray assay. Results: Thirty-eight (43%) of the 88 analyzed miRNAs (including miR-205, miR-222, and miR-1) were sgnificantly downregulated in untreated PCA compared with untreated non-neoplastic tissue, and one (miR-183) was upregulated. Twenty (23%) miRNAs (including miR-218, miR-124, and let-7b) were significantly upregulated in treated compared to untreated PCA. The expression levels of 16 of these miRNAs (including miR-9, miR-133b, and miR-27b) were reverted to values similar to untreated non-neoplastic prostatic tissue, as a result of docetaxel treatment. Conclusions: Our results indicate a potential role of miRNAs in PCA response to taxanes. A subset of miRNAs are downregulated in untreated tumors but upregulated in treated PCA to the levels compared to untreated non-neoplastic tissue, suggesting a miRNA modulation towards a non-neoplastic expression profile with neoadjuvant docetaxel treatment. Further studies are underway to evaluate the miRNA-mediated effects of taxanes in PCA.
Phase I study of imatinib mesylate (IM) and sorafenib (S) in patients (pts) with refractory castration-resistant prostate cancer (CRPC).
Authors: Nabhan Chadi , Villines Dana , Valdez Tina V. , Tolzien Kathy , Lestingi Timothy M. , Bitran Jacob D. , Susan Christner M. , Egorin Merrill J. , Beumer Jan H. 
Published: February 2017

146 Background: IM is an inhibitor of protein-tyrosine kinases including those that are over-expressed in bone metastases and primary prostatic adenocarcinoma. S is a potent inhibitor of wild-type and mutant BRAF, C-RAF, VEGFR2, VEGFR3, FLT3, and PDGFR-beta with modest activity in CRPC. We combined IM+S to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) in CRPC pts. Methods: CRPC pts with measurable disease and adequate organ function who failed chemotherapy were eligible. Dose escalation followed a 3+3 study design. Toxicity was scored following CTCAEv3. Responses were defined by RECIST1.0. IM pharmacokinetics (PK) were determined on day 15, 4 h post-dose with a validated LC-MS assay. Results: Seventeen pts were enrolled; 10 were evaluable. At dose level 0 (DL0), 6 pts received S at 400 mg S with 300 mg of IM both given daily. At DL1, 4 pts received 400 mg S twice/day with 300 mg IM daily; inevaluable pts received <1 cycle (5 withdrew consent, 1 rapid early progression, 1 non-compliant). Median age was 73 (57-89) and median PSA was 284 ng/ml (11.7–9027). Median number of prior non-hormonal therapies was 3 (1–12) and 12 pts had Gleason score ≥7 while 15 pts had bone as the major site of metastases. On DL0, 1/6 pts had DLT (gr 3 hand/foot). On DL1, 2/4 pts had DLT (1 gr 3 hand/foot, 1 gr 3 diarrhea). MTD was 300 mg IM and 400 mg S both qd. No biochemical responses were observed. Two pts on DL1 had stable disease radiographically by RECIST (overall clinical benefit for the entire cohort 20%). Median time to progression was 2 months (1-5) while median OS was 6 months (1-30+) with 3/17 patients (17%) remaining alive at a median follow-up of 21 months. Of patients enrolled, 10 had PK data, which suggested that S reduced IM clearance by 40%, resulting in 60% increased exposure (P = 0.009; two-tailed t-test on log-transformed values, compared to historic data). Conclusions: To our knowledge, this is the first report to show that IM+S can be safely combined in CRPC. The phase II recommended dose for future trials is 300 mg IM and 400 mg S, both given daily. The PK interaction might be of questionable clinical relevance because IM concentrations are within the commonly observed range.
Differences in prostate cancer survival between Denmark, Iceland, and Sweden: A high-resolution study.
Authors: Ingimarsdottir Inga Jona 
Published: February 2017

159 Background: Register-based studies have demonstrated large differences in relative survival and excess mortality following the diagnosis of PC in the Nordic countries. These differences may reflect differences in patient characteristics, diagnostics (PSA-use) and treatment strategies. This high-resolution study explores the background for the differences in PC survival between Denmark, Iceland and Sweden. Methods: Patients with newly diagnosed PC in 1997 were identified through population-based national cancer registers in Denmark and Iceland. Information on clinical findings was retrieved by reviewing hospital files. In Sweden information was gathered from two regional population-based prostate cancer registers providing both time of diagnosis and clinical information. Country specific excess mortality rates were compared adjusting for available information on known prognostic factors. Results: The overall relative survival in the cohorts was comparable to population-based results previously published. Across countries significant differences in excess mortality rates were seen. These differences were largely explained by differences in patient characteristics at diagnosis, and when adjusting for differences in patient characteristics i.e. metastatic / non-metastatic disease, clinical T-stage, and PSA level at diagnosis, the differences in excess mortality diminished or disappeared. The difference in percentage of patients with metastatic disease at diagnosis was the one factor responsible for the major differences in mortality-rates across countries. Conclusions: Register-based studies on relative survival and excess mortality following a PC diagnosis may be influenced by national differences in clinical presentation at diagnosis. Differences between countries in the proportion of patients with metastatic spread at diagnosis apparently explains most of the difference in relative survival previously reported. Further studies and cross country comparisons of survival and excess mortality for PC should adjust for differences in patient characteristics, mainly TNM.