bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduction of nodal micrometastases in patients with histological node-negative esophageal cancer after neoadjuvant treatment.
Authors: Wang D. , Smit J. K. , Hollema H. , Plukker J. T. 
Published: February 2017

73 Background: Neoadjuvant chemoradiation (CRT) is important in the treatment ofesophageal cancer. Rationales are tumor-downstaging and elimination of micrometastases improving resectability and curability rate. In this study we evaluated the effect of neo-adjuvant CRT on nodal micrometastases (NMM) in pN0 esophageal cancer patients. Methods: From a prospective database, we selected a matched group of patients on cT-stage, histological type and treatment without (group 1) or with neo-adjuvant CRT (group 2). Patients were staged by EUS, PET-scan, CT-scan and EUS guided cytology. CRT was given in a randomized clinical trial and consisted of paclitaxel 50 mg/m2 and carboplatin AUC = 2 for 5 weeks and concurrent radiotherapy (41.4 Gy/23 frs). All patients (n = 19) underwent a curative intended transthoracic esophagectomy with extended 2-field nodal dissection. After reviewing routine pathological examination all tumors were confirmed as stage pN0. Four sections of every examined lymph node (n = 261) were made at different levels according to a sentinel node protocol and further analyzed immunohistochemically with anti-CK8/18 (CAM 5.2) to detect NMM. Results: Patients characteristics were equally distributed. All patients had a microscopically radical (R0) resection. In group 2 (n = 9) the response rate was 55% which was complete (CR) in 33%. The median number of resected nodes was comparable: 15 ± 6.5 and 15 ± 5.6 in both groups. Thirtheen of the 261 (5%) pN0 nodes in these 19 pts contained NMM. In group 1 (n = 10); 12 of the 136 (9%) examined pN0 lymph nodes were positive and in group 2 only one of the 125 (0.8%) examined pN0 nodes was positive (p = 0.003). NMM were found in 7 pts (70%) in group 1 and in only one patient (11%) in group 2 (p = 0.02). Interestingly, this last patient had responded well to CRT. Conclusions: Neo-adjuvant CRT seems to have a significant impact on the numbers of NMMs in esophageal cancer. Based on the presence of NMM even in patients with good responses, we still advocate a curatively intended nodal dissection. No significant financial relationships to disclose.
Validation study of sentinel lymph node mapping using radio- and dye-guided methods in gastric cancer: 431 cases at a single institution.
Authors: Niihara M. , Takeuchi H. , Kamiya S. , Kaburagi T. , Oyama T. , Saikawa Y. , Wada N. , Takahashi T. , Nakamura R. , Kitagawa Y. 
Published: February 2017

76 Background: Some papers have reported that sentinel lymph node (SLN) concept can be applied in patients with early gastric cancer, in particular clinically T1N0M0 or T2N0M0 with a tumor diameter of 4cm or less. Little is, however, available on the SLN study with the other criteria than listed above. The aim of the present work was to investigate the accuracy of the SLN biopsy of gastric cancer with various stages and evaluate the indication for SLN navigated gastrectomy. Methods: A total of 431 consecutive patients were diagnosed with operable gastric cancer during the period April 1999 through December 2007. Reasons for inclusion were, in principle, T1N0M0 or T2N0M0 gastric cancer. However, several patients diagnosed preoperatively with T3N0M0, T2N1M0, remnant gastric cancer, multiple gastric cancers and additional treatment after endoscopic therapy were also enrolled in this study according to their request. All patients underwent a radical gastrectomy with SLN mapping with an informed consent. The SLNs were identified using both radio-guided and dye-guided method. Results: Detection rate of hot and/or blue node was 95.8% (413/431). The accuracy of metastatic status based on SLN was 97.6% (403/413). In six of 10 false-negative cases, some clinical backgrounds and problems were present; scirrhous gastric cancer, the tumor penetration of serosa, multiple lesions, remnant gastric cancer after partial resection and the technical issue of tracer injection. Nine of these 10 false-negative cases had the metastatic lymph nodes within only the sentinel basins. Specifically, in the group of clinically T1N0M0 untreated gastric cancer with a tumor diameter of 4 cm or less, there were only 3 false- negative cases. In addition, all the metastatic lymph nodes of the 3 cases located within the sentinel basins. Conclusions: Our study suggested that SLN concept for untreated early gastric cancer could be validated. The sentinel basin dissection might be used to advantage to improve curativity for gastric cancer. No significant financial relationships to disclose.
The effect of preoperative chemotherapy on lymph node yield in gastric cancer.
Authors: Dikken J. L. , Krijnen P. , Van De Velde C. J. , Verheij M. , Gonen M. , van Grieken N. C. , Tang L. H. , Brennan M. F. , Coit D. G. 
Published: February 2017

80 Background: While a minimum of 15 lymphnodes (LNs) should be evaluated for accurate staging of gastric cancer, LN yield in western countries is generally low. With the increasing use of preoperative chemotherapy, it is unknown what the effect of this treatment is on lymph node yield. The aim of the study is therefore to determine whether preoperative chemotherapy influences the number of LNs that can be obtained from specimens of patients who underwent curative surgery for gastric adenocarcinoma. Methods: In1,205 patients from a high-volume U.S. center and 1,220 patients from the Netherlands Cancer Registry (NCR) who underwent a total or distal gastrectomy with curative intent for gastric adenocarcinoma, the LN yield was compared between patients who received preoperative chemotherapy and patients who received no neoadjuvant therapy. Multivariate Poisson regression was used to identify significant predictors of LN retrieval. Results: Of the 2,425 patients who underwent a gastrectomy, 340 patients (14%) received preoperative chemotherapy. Median LN yields were 23 in the U.S. institution and 10 in the NCR. Separate multivariate analyses of the U.S. institution data and the NCR population showed in both groups that preoperative chemotherapy was not associated with a significant difference in LN yield (Table). Factors that were associated with higher LN yield were the same in both groups: female sex, younger age (6% more nodes with every 10 years decrease in age), total gastrectomy (vs. distal gastrectomy) and increasing tumor (T) stage. Conclusions: In both a high-volume cancer center, and a population-based cancer registry, female sex, younger age, total gastrectomy and advanced tumor stage were associated with an increase in lymph node retrieval in surgical specimens. Preoperative chemotherapy did not influence lymph node yield after a resection for gastric cancer. The threshold for what should constitute an adequate assessment of regional lymph nodes after curative surgery for gastric cancer should not be changed after administration of preoperative chemotherapy. [Table: see text] No significant financial relationships to disclose.
Value of the primary tumor initial standardized uptake value (iSUV) of 18F-fluorodeoxyglucose positron emission tomography (PET) to predict overall survival (OS) in patients with esophageal or gastroesophageal junction carcinoma undergoing definitive chemoradiotherapy.
Authors: Suzuki A. , Xiao L. , Hayashi Y. , Welsh J. , Lin S. H. , Lee J. H. , Bhutani M. S. , Hofstetter W. L. , Mehran R. J. , Ajani J. A. 
Published: February 2017

82 Background: The value of iSUV of PET for predicting OS is unclear in patients with advanced esophageal or gastroesophageal carcinoma treated with definitive chemoradiotherapy. We tested the hypothesis that iSUV would correlate with OS and recurrence free survival (RFS). Methods: We performed retrospective analysis, selecting patients with esophageal or gastroesophageal carcinoma who had a pretreatment PET and endoscopic ultrasonography (EUS) and who received definitive chemoradiotherapy from 2002 to 2008. Correlations were performed with continuous and dichotomized iSUV, baseline EUS results, OS, and RFS. Results: Two hundred and nine patients were analyzed. The median OS time was 20.7 months (95% CI: 18.8-26.3 months) and the median RFS time was 11.2 months (95% CI: 9.44, 14.34). OS rate and RFS rate at 3 years were 35.7% (95% CI: 29.0-43.9%) and 24.8% (95 % CI: 19.1–32.1 %). The median iSUV was 12.7 (range: 0–51). In univariate analysis, iSUV was associated with OS (Cox model, P = 0.012; log-rank test, P = 0.002) and RFS (Cox model, P = 0.0003; log-rank test, P < 0.0001). In multivariate analysis, dichotomized iSUV cut off by median was associated with OS (P = 0.024) but not RFS (P = 0.11). Conclusions: Data from our study suggests that higher iSUV is associated with poor survival. Baseline PET may become a useful stratification factor in randomized trials and for individualized therapy. No significant financial relationships to disclose.
Overall survival benefit with masitinib mesylate in imatinib-naive, locally advanced, or metastatic gastrointestinal stromal tumor (GIST): 4-years follow-up of the French Sarcoma Group phase II trial.
Authors: Blay J. , Le Cesne A. , Bin Bui N. , Bouche O. , Adenis A. , Julien D. , Cioffi A. , Moussy A. , Hermine O. 
Published: February 2017

85 Background: Masitinib is a novel tyrosine kinase inhibitor which, in vitro, has greater activity and selectivity than imatinib (IM) against both wild-type KIT receptor and its mutated form in the juxtamembrane region (IC 50=100 nM versus 200 nM for IM, 3 nM versus 27nM and 40 nM versus 120nM, respectively, for exons 9,11, and 13). This multicenter phase II study evaluated efficacy and safety of masitinib as a first-line treatment of advanced GIST. Methods: IM-naïve patients with inoperable, locally advanced or metastatic GIST received oral masitinib (7.5 mg/kg/day) until progression, refusal or toxicity. Efficacy variables included response rate, best response (RECIST), progression-free survival (PFS) and overall survival (OS). Initial results were previously reported in EJC 2010. We present here the same series with updated PFS and OS (median follow up of 48 months). Results: 30 patients with a median age of 58 years (60% of males) were included from June 2005 to April 2007 in five French institutions. At the cut-off date (31 august 2010), 9 patients are still under treatment with a median treatment duration of 41 months (min=33, max=52). Two additional progressions have been reported for a total of 14 events (13 progressions and 1 death). Updated median PFS is 41 months (95% CI: [17.5; NR]) with PFS rates of 60% [39; 77], 56% [35; 73] and 45% [24; 64] respectively at 2, 3 and 4 years. With 8 patients dead, median OS is not yet reached with OS rates of 90% [72; 97], 87% [68; 95] and 74% [52; 87], respectively, at 2, 3, and 4 years. The main frequent relevant grade 3 toxicities were: rash (10%), neutropenia (7%) and abdominal pain (7%) with one patient presented a grade 4 skin exfoliation. No other relevant long-term toxicities were reported and no more patients discontinued treatment due to suspected toxicity. Conclusions: The long term results observed with masitinib confirm a very interesting activity with prolonged PFS and OS. These results support the head to head comparison with imatinib in the currently ongoing phase III randomized clinical trial in first line locally advanced or metastatic GIST patients. [Table: see text]
The Prostate Cancer Clinical Trials Consortium (PCCTC) bone scan data capture tool for clinical trials using Prostate Cancer Working Group 2 (PCWG2) criteria: Effect on data accuracy and workload.
Authors: Morris M. J. , Farrelly J. S. , Fox J. J. , Dennis E. R. , Schwartz L. H. , Schöder H. 
Published: February 2017

121 Background: PCWG2 Concensus Criteria proposed time-to-event endpoints in early phase clinical trials. Chief among these was time to radiographic progression for bone scintigraphy (BS), based on a standardized definition with additional rulesets to account for early flare. The PCCTC created a tool to operationalize these definitions in clinical trials. We tested the impact of the tool on clinical trial workload and data adequacy. Methods: The BS capture tool was vetted and amended through nine versions by a multidisciplinary group from PCCTC participating institutions. Accruals at Memorial Sloan-Kettering Cancer Center on two phase III trials using the same drug, contracting research organization (CRO), and electronic data capture system were analyzed. The first trial did not use the PCCTC tool. The second incorporated the tool in its data collection plan and case report form. Workload and data capture adequacy for each trial were determine by examining the total number of imaging queries from the database query reports obtained from the CRO as a function of the total number of scans and patients. Results: Data from this analysis are found in the table . The relative number of queries per scan was reduced by 85.33% by use of the tool. The queries:scan ratios were 0.82 versus 0.12 before and after the use of the tool respectively; likewise, the ratios of queries: patient were 2.81 vs. 0.44. Conclusions: Using the PCCTC BS tool to standardize data capture and operationalize PCWG2 radiographic progression criteria, imaging data are more completely reported and workload for study research staff decreased. The reproducibility and feasibility of the BS tool is further being tested in two ongoing phase III studies in which PCWG2 criteria are being clinically qualified. These efforts to quantitate, standardize, and qualify imaging data advance the goal of developing an imaging biomarker in metastatic prostate cancer. [Table: see text] No significant financial relationships to disclose.
Use of variation in sex steroid methyl transferases to predict efficacy of androgen-deprivation therapy (ADT) in advanced prostate cancer.
Authors: Kohli M. , Mahoney D. W. , Chai H. S. , Hillman D. W. , Rider D. R. , Costello B. A. , Cerhan J. R. 
Published: February 2017

14 Background: We evaluated the association of germline variation in genes regulating hormonal pathways with duration of treatment response in prostate cancer patients receiving ADT, focusing on genes in the androgen biosynthesis (the C4 Δ; C5 Δ; C21 CYP pathways and the alternate “backdoor pathway”) and metabolism pathways. Methods: We successfully genotyped 747 single nucleotide polymorphisms (SNPs) from 84 genes in a cohort of 304 patients with advanced prostate cancer who progressed on ADT. Tagging SNPs with a minor allele frequency (MAF) of >5% and r2 ≥0.8 were selected from HapMap, NIEHS and Seattle SNP databases. The primary endpoint was time to ADT failure, and we conducted a gene-level test (principal components), along with individual SNP level tests adjusted for patient age and Gleason score. To account for multiple testing, we calculated the false discovery rate (FDR), and FDRs of 0.10 were considered noteworthy. Results: The median age of the cohort at ADT failure was 72 years (range 65-78 years), and the overall median time to ADT failure was 3.21 years (IQ [25-75]: 1.54-6.20 years). At the gene level, TRMT11 (tRNA methyltransferase 11 homologue) showed the strongest association with time to ADT failure (p<0.0008; adjusted p-value for FDR-0.068). Two of four TRMT11 tag SNPs were associated with time to ADT failure. The first was the intronic SNP rs1268121 (A>G) with a MAF of 15%, for which there was a positive association of median time to ADT failure with the number of variant alleles (p=0.023): 3.1 years for 0, 4.1 years for 1, and 5.9 years for 2 variant alleles. The second was the SNP rs6900796 (A>G) in the 3' untranscribed region with a MAF of 49%, for which the median time to ADT failure was 2.6 years for 0, 2.5 years for 1, and 3.8 years for 2 variant alleles (p=0.023). Four additional genes showed an association with ADT response at the p<0.10 level, including LOC390956, PRMT3, SLC7A6OS, and WBSCR22, although all FDRs were >0.95. Conclusions: Variation in TRMT11 was associated with time to ADT failure. Confirmation of these findings in an independent cohort is needed. No significant financial relationships to disclose.
Dose-finding and efficacy phase II study of inecalcitol, a new VDR agonist, in combination with docetaxel-prednisone regimen for castration-resistant prostate cancer (CRPC) patients (pts).
Authors: Medioni J. , Deplanque G. , Ferrero J. , Maurina T. , Rodier J. P. , Raymond E. , Allyon J. , Renaux S. , Dufour-Lamartinie J. , Oudard S. 
Published: February 2017

142 Background: Inecalcitol is a novel vitamin D receptor (VDR) agonist which shows high antiproliferative effects in human cancer cell lines and a 100-fold lower hypercalcemic activity than calcitriol the natural ligand of VDR. Methods: Escalating dosages of inecalcitol were combined to chemotherapy in naive metastatic CRPC patients. Safety and efficacy were evaluated in groups of 3-6 pts receiving inecalcitol every other day, daily or twice a day on a 21-day cycle in combination with docetaxel (75mg/m2 q3w) and oral prednisone (5mg bid). Pts received up to six cycles unless unacceptable toxicity or disease progression. Primary endpoint was dose limiting toxicity (DLT) defined as G3 hypercalcemia within the first cycle. Efficacy endpoint was PSA response defined as ≥30% decline within 3 months. Results: Eight dose levels from 40 to 8,000 μg have been evaluated in 54 pts; 83 % had bone metastases, 13% had visceral disease only. Median age was 71 years (range, 49-87), median Gleason score (Gs) 7 and median PSA 28.5 ng/mL (range, 0.8-962.4). DLT occurred in 2/4 patients receiving 8,000 μg/day after 1 and 2 weeks of treatment. Calcemia normalized in few days after interruption of treatment. The 2 other experienced only G2 and were stepped down to 4,000 μg. After dose reduction, calcemia remained within normal ranges and G1.The maximum tolerated dose is defined at 4,000 μg qd. Most of adverse events reported were grade 2. G3-4 were mainly hematological toxicity. Frequency of AEs related to docetaxel did not seem to be modified.82% of the patients had ≥30% PSA decline within 3 months of treatment whereas in historical data around 65% are responder with docetaxel as a single agent. PSA response was observed after 1 cycle of treatment in 43% of the patients. Time to biochemical relapse defined as an increase of 25% over nadir was 169 days. Conclusions: High antiproliferative daily dose of inecalcitol, a new VDR, agonist has been safely used in combination with docetaxel in CRPC patients. This combination treatment shows encouraging PSA response (> 30% PSA response: 82%). A multicenter randomized double blind phase III study is forecasted to confirm these results. [Table: see text]
Carboplatin plus weekly docetaxel as salvage chemotherapy in docetaxel-resistant and castration-resistant prostate cancer (DRPC).
Authors: Reuter C. W. , Morgan M. A. , Gruenwald V. , Fenner M. , Ivanyi P. , Ganser A. 
Published: February 2017

172 Background: Cabacitaxel has recently been approved by the FDA as second-line chemotherapy for patients progressing during or after first-line docetaxel chemotherapy. However, cabacitaxel treatment is hampered by high costs and toxicity. Carboplatin in combination with docetaxel may also be effective in DRPC. Platinum(II)-complexes have been shown to lower testosterone levels by inhibiting 3β-hydroxysteroid dehydrogenase and 17α hydroxylase (Schertl et al. J Cancer Res Clin Oncol. 2007;133:153-67). Methods: Docetaxel failure/resistance was defined according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Since February 2005, 55 consecutive DRPC pts were treated with at least two cycles of carboplatin AUC5 iv for 30 min on day 1 every 4 weeks (q4w), docetaxel at a dose of 35 mg/m2 iv for one hour on days 1, 8, (15) plus prednisone 2×5mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG2 recommendations. Free testosterone levels were measured before and during carboplatin/docetaxel chemotherapy (n=25). Results: Response of prostate-specific antigen (PSAR; ≥50% PSA) was observed in 28/55 (50.9%) patients. At the time of the current analysis the median follow-up time was 11.9 months and 32/55 patients had died. Median progression-free survival (PFS) for all patients was 7.5 months (CI 95% 5.7, 9.3) and median overall survival (OS) was 17.1 months (CI 95% 10.3, 23.9). In PSAR, PFS was 13.6 (CI 95% 7.8, 19.4) months versus 4.3 (CI 95% 2.9, 5.7) months in PSANR (p<0.001; hazard ratio HR 0.159) and OS was 24.4 months (CI 95% 18.1, 30.8) versus 8.1 (CI 95% 3.4, 12.8) months (p<0.001; HR 0.208). This regimen was reasonably well tolerated, with leukopenia/neutropenia as the most common reversible grade 3/4 toxicity (44.2/40.4%). Median free testosterone levels were 1.05 pg/ml before and 0.26 pg/ml during carboplatin/docetaxel treatment (p<0.01). Conclusions: Our data suggest that carboplatin/docetaxel may be an important therapeutic second-line treatment option for DRPC patients by inferfering with the testosterone synthesis. No significant financial relationships to disclose.
Can PSA testing stop 10 years after radical prostatectomy?
Authors: Loeb S. , Feng Z. , Ross A. , Trock B. J. , Humphreys E. B. , Walsh P. C. 
Published: February 2017

179 Background: Biochemical recurrence (BCR) most frequently occurs within the first five years following radical prostatectomy. Prior studies have suggested an association between lower-risk disease features and BCR at 5 years postoperatively. The objective of our study was to determine predictors of BCR ≥10 years after radical prostatectomy, and to examine the relationship between timing of BCR with the subsequent risk of metastases and cancer-specific mortality. Methods: Among 10,609 men from our institutional radical prostatectomy database, we identified 1684 men with BCR (PSA >0.2 ng/ml) without prior hormonal or radiation therapy. These men were classified into by the time of BCR: early (<5 years), intermediate (5-10 years), and late (>10 years). Univariable and multivariable models were used to examine the association of clinico-pathologic variables with the timing of BCR. We also examined metastasis-free and cancer-specific survival based upon the timing of BCR. Results: Of BCR, 77.0%, 16.6%, 4.9%, and 1.5% occurred at <5, 5-10, 10-15, and >15 years postoperatively. Late recurrences were associated with more favorable pathologic features, and were unlikely to develop metastases or prostate cancer-specific mortality. Conclusions: The majority of BCR occurs within 10 years of surgery. Although 6.4% of BCR occurred at ≥10 years, these patients were unlikely to subsequently develop metastases or die from prostate cancer. Patients who remain free from progression at 10 years postoperatively should be counseled that their risk of subsequent cancer-related morbidity and mortality is low. No significant financial relationships to disclose.