bluuebunny/crossref_metadata_2025_split huggingface dataset:
Truncation of BRAF and Raf1 in prostate cancer in China.
Authors: Lu Yong-Jie , Liu Xiaoyan , Mao Xueying , Hylands Lucy , Clark Jeremy , Cooper Colin , Ren Guoping 
Published: February 2017

77 Background: Chromosome translocations and fusion genes have been identified as common events in carcinomas in recent years and TMPRSS2:ERG fusions have been found in about half of human prostate cancers. However, by genome-wide analysis of Chinese prostate cancer cases, we found that certain genomic alterations, commonly identified in prostate cancer samples from the Western countries, occurred at a very low frequency in China, including the fusion of TMPRSS2:ERG. In 2010, recurrent fusion genes involving the RAF family gene BRAF and Raf1 were identified (Palanisamy et al, Nature Med. 16:793). Although the frequency of fusions involving BRAF and Raf1 are at a much lower frequency than fusion of TMPRSS2:ERG, BRAF and Raf1 are drugable, making them potential therapeutic targets. As the TMPRSS2:ERG fusion is infrequent in Chinese prostate cancers, we investigated if fusions involving BRAF and Raf1 occur at a higher frequency in prostate cancer in China than in Western countries. Methods: We used the fluorescence in situ hybridization signal split apart approach on prostate cancer samples made into tissue microarrays to detect the frequency of BRAF and Raf1 truncations. Three BAC probes on each side (5’ and 3’) of the two genes were labeled differentially using biotin and digoxigenin and subsequentially detected as red and green fluorescent signals, respectively. Results: We found that BRAF was truncated in four (two split signals, one 5’ deletions and one 3’ deletions) of the 193 informative cases (2.07%) and RAFaf1 (two 5’ deletions and one split signals) was truncated in three of 201 informative cases (1.49%). Although in some cases, three or four copies of these genes were detected, extensive copy number gain caused by amplification was not detected. Conclusions: These results indicate that truncations and potentially fusion of BRAF and Raf1 exist in Chinese prostate cancer, but at a similar low frequency as found in the Western samples (6/349 for BRAF and 4/450 for Raf1). Further studies are required to confirm the functional consequence of these truncations and to evaluate the therapeutic value of targeting these genes in this sub-group of prostate cancers.
C11-acetate PET for docetaxel prednisone (DP) response assessment in castrate-resistant prostate cancer (CRPC).
Authors: Sharma Nancy , Menda Yusuf , Boles-Ponto Laura , Vaena Daniel A. 
Published: February 2017

83 Background: C11-acetate (acetate) positron-emission tomogram (PET) has shown promise in detection of metastasis in prostate cancer in recent studies. Our study tested the feasibility of acetate-PET to predict early response to DP in CRPC. Methods: Men with metastatic CRPC for whom DP was indicated were enrolled in a prospective study of acetate-PET imaging and bone scans. Patients (pts) were imaged with both modalities at study entry and after 3 cycles of DP. DP was continued beyond cycle 3 until PCWG2-defined progression or toxicity. Treating physicians were blinded to acetate-PET results. No pts were on statins. The study was IRB-approved. Results: 6 pts with documented bone metastases were imaged (5 both pre and post-therapy.) Pre-therapy acetate-PET identified osseous metastases in all 6 pts. Remarkably, in one pt with previous radiation therapy, pre-therapy acetate-PET was negative for disease in the radiated area whereas bone scan showed persistent activity. The median number of DP cycles was 7 (5-16). 4 pts had ≥ 50% PSA decline. The median time to progression (TTP) was 5 months (mo). Of the 4 pts with PSA response, 2 had response on acetate-PET with TTP 5 mo and 10 mo respectively. One pt had > 50% PSA response but progression after 3 cycles based on PET, and met PCWG2 criteria for progression at 3.5 mo. The 4th pt with PSA response had stable findings on post-therapy PET and had >10 mo TTP. The pt who had no PSA response had stable post-therapy PET and had 2 mo TTP. Bone scan was stable in 4 pts and showed progression in 1 pt. Conclusions: Response or progression on acetate-PET can be seen after a few chemotherapy cycles for CRPC. This study supports the exploratory inclusion of acetate-PET in future therapeutic clinical trials, with the potential to enhance the early prediction of treatment outcome. Acetate-PET might also allow more precise identification of viable target lesions than bone scan.
Radiation Therapy Oncology Group (RTOG) 9413: Randomized trial comparing whole pelvic radiotherapy (WPRT) to prostate only (PORT) and neoadjuvant hormone therapy (NHT) to adjuvant hormone therapy (AHT).
Authors: Roach Mack , Yan Yan , Lawton Colleen Anne , Hsu I-Chow Joe , Lustig Robert A. , Jones Christopher U. , Rotman Marvin , Zeitzer Kenneth Lee , Werner-Wasik Maria , Kim Harold , Thomas Charles R. , Shipley William U. , Sandler Howard Mark 
Published: February 2017

96 Background: RTOG 9413 demonstrated that NHT+WPRT improved progression-free survival (PFS) compared to NHT+PORT, WPRT+AHT and PORT+AHT. We update primary and secondary endpoints (SE): biochemical failure (BF), time to metastasis (Mets), prostate specific survival (PSS) and overall survival (OS). Methods: RTOG 9413 opened on April 1, 1995, and closed on June 1, 1999, with 1275 eligible pts who were required to have a risk of lymph node (LN) involvement >15% but LN-positive pts were ineligible. They were stratified by T Stage, GS (<7 vs 7-10) and PSA (>30 vs < 30ng/ml) and randomized to PORT +/- WPRT to 70 Gy and NHT or AHT. Hormonal therapy (HT) consisted of flutamide, and leuprolide or goserelin, monthly x 4 mos, beginning 2 mos before RT and continued until RT is completed (NHT) or beginning at the completion of RT (AHT). For this analysis PFS was defined as the first occurrence of local/regional or LN progression, Mets, BF (PSA nadir+2ng/mL), or death from any cause. PSS is defined as a death due to prostate cancer, treatment toxicity or unknown causes with local progression, Mets or BF. Results: For the entire cohort WPRT or NHT did not appear to improve any endpoint compared with PORT or AHT, (although there was a trend for improvement in regional failure for WPRT vs PORT, (p=0.07)). However, there were complex sequence/volume dependent interactions between HT and RT and statistically significant differences between the 4 arms in PFS (p=0.03). There was a trend for NHT+WPRT to improved PFS compared to NHT+PO (p=0.07) and WPRT+AHT (p=0.04). NHT+WPRT was associated with an increased risk of late GI toxicity, 5% compared to 0.6%, 2% and 2% for NHT+PORT, WPRT+AHT and PORT+AHT (p<0.001) but not in GU late toxicity. Conclusions: The failure to improve SE or definitively impact PFS may reflect sample size, pt selection, and inadequate RT doses. RTOG 0924 will test the hypotheses that modern techniques and doses will improve OS without increasing late toxicity.
Relationship of time to testosterone (T) and PSA rises during the first “off treatment” interval (1OFF) of intermittent androgen deprivation (IAD) with time to castration resistance (CRPC) and prostate cancer mortality (PCM) in men with biochemical relapse (BR).
Authors: Yu Evan Y. , Kuo Kevin F , Hunter-Merrill Rachel , Gulati Roman , Hall Suzanne P , Gambol Teresa E , Etzioni Ruth D , Higano Celestia S. 
Published: February 2017

99 Background: A recent phase III trial of intermittent vs. continuous AD supports IAD as standard of care for men treated with AD for BR. To identify potential factors during 1OFF prognostic for time to CRPC or PCM, relationships with times to T and PSA rises from our prospective trial of IAD in men with BR were analyzed. Methods: 72 patients were treated with IAD, each cycle consisting of 9 months of leuprolide and flutamide followed by a variable “off treatment” interval. T and PSA were followed monthly; AD was resumed when PSA reached a pre-specified value. Cycles repeated until CRPC, defined as ≥2 PSA rises with T<50 ng/dL. We evaluated patients who completed 1OFF and reached T>50 with a Cox proportional hazards model, controlling for age at study entry, to quantify association of time to first T>50 with time from this point to CRPC or PCM. Similarly we quantified association of PSA rise during 1OFF and after first T>50 with these endpoints. Results: A longer time to PSA rise during 1OFF or after T>50 was associated with longer time to CRPC, while longer time to first T>50 was marginally associated with shorter time to PCM. Specifically, a 30-day increase in time to PSA rise during 1OFF or after T>50 was associated with a 21% or 27% reduction in the risk of CRPC, while a 30-day increase in time to first T>50 was associated with a 39% increase in the risk of PCM. Conclusions: That longer time to PSA rise during 1OFF was associated with longer time to CRPC is not surprising, but the association between longer time to first T>50 and time to PCM has not been reported. To validate these findings, an extended analysis is underway and will be presented. [Table: see text]
Cosmetic outcome after intraoperative radiotherapy or external beam radiotherapy for early breast cancer: An objective assessment of patients from a randomized controlled trial.
Authors: Keshtgar Mohammed R. , Williams Norman R. , Corica Tammy , Bulsara Max , Saunders Christobel , Flyger Henrik , Bentzon Niels , Cardoso Jaime S. , Michalopoulos Nikolaus , Joseph David John ,   on behalf of the TARGIT Trialists' Group
Published: February 2017

59 Background: The international randomised contolled TARGeted Intraoperative radioTherapy (TARGIT) trial has demonstrated non-inferiority between the novel technique of TARGIT (intra-operative radiotherapy with Intrabeam) and conventional whole-breast external beam radiotherapy (EBRT) in women with early breast cancer, in terms of the primary outcome measure of risk of local relapse within the treated breast. With very low recurrence rates, cosmesis becomes an increasingly important outcome of breast conserving treatment with both surgery and radiotherapy. This study was performed to determine if the single high dose of TARGIT leads to impaired cosmesis. Methods: A validated, objective assessment tool for evaluation of cosmetic outcome was used. Frontal digital photographs were taken at baseline (before TARGIT or EBRT) and yearly thereafter for up to five years. The photographs were analysed by BCCT.core software which produces a composite score based on symmetry, colour and scar. Results: 342 patients were assessed, all over 50 years old with a median age at baseline of 64 years (IQR 59 to 68). The scores were dichotomised into Excellent and Good (EG), and Fair and Poor (FP). There were statistically significant increases in the odds of having an outcome of EG for patients in the TARGIT group relative to the EBRT group at year 1 (OR = 2.07, 95% CI 1.12 to 3.85, p = 0.021) and year 2 (OR = 2.11, 95% CI 1.0 to 4.45, p = 0.05). Conclusions: Following an objective assessment of aesthetic outcome in patients from a randomised setting, this study demonstrates that those treated with targeted intraoperative radiotherapy have a superior cosmetic result compared with those patients who received conventional whole-breast external beam radiotherapy.
Estimation of travel time and costs required for patients with cancer to receive outpatient treatment using electronic medical record data.
Authors: Isshiki Takahiro , Kimura Yuko , Takei Naoko , Hagino Noboru , Komatsu Tsunehiko 
Published: February 2017

270 Background: Cancer creates a tremendous financial burden. Cancer-related costs are categorized into direct, indirect and psychosocial costs. Although there have been many reports on medical care costs, which are direct, those on other costs are extremely scarce. We estimated travel time and costs required for cancer patients to receive outpatient treatment. Methods: We studied 524 cancer patients given anti-cancer treatment between February 2009 and December 2012 at the Outpatient Chemotherapy Center of Teikyo University Chiba Medical Center. Address data were extracted from Data Warehouse electronic medical records, and travel distance and time required for outpatient treatment were calculated via MapInfo and ACT Distance Calculator Package. Transportation costs were estimated on the basis of ¥274 (= $3.00) per kilometer. Results: Average round-trip travel distances, times, and costs by cancer type are shown below. Average round-trip travel distance, time, and cost for all patients were 26.7 km, 72.5 minutes, and ¥7,303 ($79.99), respectively. Conclusions: Cancer patients incurred a travel cost of approximately ¥4,000 to ¥9,000 ($40.00 to $100.00) for each outpatient treatment. With population aging, seniors living alone and senior households are increasing, and outpatient visits are becoming a common burden. [Table: see text]
Association of 2-O, 3-O desulfated heparin (ODSH) plus combination gemcitabine (G)/nab-paclitaxel (A) with preliminary benefit in untreated metastatic pancreatic cancer.
Authors: Sigal Darren , Marcus Stephen G , Rosen Peter J. , Cohen Steven J. , Lee Peter , Nguyen Timmy , Gribbin Thomas Edward , Quintana Diez Pedro , Borad Mitesh J. 
Published: February 2017

284 Background: ODSH, a low anticoagulant heparin derivative, interferes with several important pancreatic cancer cell survival pathways. A randomized phase II trial was initiated to determine if ODSH improves the activity of G/A, a promising pancreatic cancer investigational therapy. Preliminary data are presented here for the first 10 patients administered ODSH as part of an initial run-in phase prior to patient randomization. Methods: Patients with previously untreated, metastatic pancreatic cancer were treated with G (1,000 mg/m2) and A (125 mg/m2) plus ODSH (4 mg/kg bolus followed by a 48 hr. continuous IV infusion at a dose of 0.375 mg/kg/hr) on days 1, 8, and 15 every 28 days until disease progression or unacceptable toxicity. Patients were required to have ECOG ≤ 1 and appropriate blood and liver function levels. The primary endpoint was progression-free survival (PFS). Results: 10 patients (median age, 66 years) were administered up to 5 cycles of G/A plus ODSH. Per RECIST criteria, a partial response (PR) was achieved in 5 patients (50%) and the median PFS will exceed 6 months. Disease control (PR or stable disease for > 16 weeks) occurred in all 10 patients. Of 9 patients with baseline elevated CA 19-9 levels, 8 had > 60% reduction. ODSH was well tolerated and unexpectedly appeared to preserve marrow function as no patients had grade 3/4 thrombocytopenia or grade 4 neutropenia during any of the cycles. Conclusions: Although G/A and FOLFIRINOX are important advances, additional progress is necessary for metastatic pancreatic cancer patients. ODSH may interfere with pancreatic cancer invasion, metastasis, and chemo-resistance by inhibiting P- and L-selectins, heparanase, and the HMGB1-RAGE axis, respectively, suggesting that ODSH may enhance chemotherapy activity. This preliminary analysis in a small number of patients is encouraging and consistent with a previous report for this regimen (Von Hoff, J Clin Oncol, 2011). ODSH has also been very well tolerated and early data suggests that it may preserve platelet and neutrophil levels. Further follow-up of the ongoing randomized phase II trial is warranted. Clinical trial information: NCT01461915.
FOLFERA: A randomized phase II study of irinotecan, 5-fluorouracil (5-FU), and folinic acid (FOLFIRI) with or without addition of the endothelin receptor antagonist (ETAR) zibotentan in patients with metastatic colorectal cancer after failure of oxaliplatin-containing chemotherapy.
Authors: Thomas Anne L. , Casbard Angela Claire ,   FOLFERA Trial Management Group
Published: February 2017

406 Background: Zibotentan (Z) is an oral specific ETAR antagonist. The ETAR is over expressed in colorectal cancer, and pre-clinically, antagonism of the ETAR has been shown to enhance cytotoxicity when combined with cytotoxics such as 5-FU. This multi-center, randomized, double-blind, placebo-controlled phase II study evaluated the safety and anti-tumor activity of irinotecan and 5-FU (as the FOLFIRI regimen) in combination with Z in advanced colorectal cancer. Methods: Patients (pts) with advanced colorectal cancer who had progressed after oxaliplatin-containing chemotherapy (FOLFOX) were randomized (1:1) to receive 10 mg O.D Z/placebo (continuous dosing) with standard dose FOLFIRI for a maximum of 12 cycles. Z /placebo could be continued until progression or unacceptable toxicity in those patients with a documented response. The primary objective was progression–free survival (PFS) with secondary endpoints of safety and blood and archival tumor samples collected for translational work including circulating tumour cell (CTC) analysis. This study was run as part of the AZ/NCRN alliance, endorsed by Cancer Research UK (CRUKE/09/023) and coordinated by the Wales Cancer Trials Unit, Cardiff University. Results: A total of 111 patients were recruited: 61% men, median age of 62 years. Z was well tolerated with G3/4 toxicity balanced between both groups (34/55 patients in Z and 38/56 in placebo group). The study was terminated before the planned number of pts (122) were recruited due to lack of efficacy of the drug in two other tumour types. Median PFS was 4.0 months in the Z group and 7.4 months in the placebo group (HR=1.86, 95% CI 1.20 to 2.87, p=0.005). The CTC analysis in relation to outcome in the placebo group will be presented. Conclusions: Zibotentan does not have anti-cancer activity in combination with FOLFIRI in patients with colorectal cancer treated with previous FOLFOX. Taken in consideration with the other trial data we do not recommend the further development of zibotentan in oncology. Clinical trial information: 73199181.
Final results of first European phase II trial of intravenous cetuximab (Cet) and hepatic artery infusion of irinotecan, 5-fluorouracil, and oxaliplatin in patients (pts) with unresectable liver metastases from wt KRAS colorectal cancer (LM-CRC) after systemic treatment failure (OPTILIV, NCT00852228).
Authors: Levi Francis , Boige Valerie , Hebbar Mohamed , Smith Denis , Lepère Céline , Focan C. N. J. , Guimbaud Rosine , Carvalho Carlos , Tumolo Salvatore , Innominato Pasquale F. , Ajavon Yves , Truant Stephanie , Castaing Denis , De Baere Thierry , Kunstlinger Francis , Karaboué Abdoulaye , Bouchahda Mohamed , Rougier Philippe R , Adam Rene , Ducreux Michel ,   ARTBC International
Published: February 2017

466 Background: Multiple, large and bilateral LM-CRC can be downsized with chemotherapy (chemo) and resected with curative intent in ~15% pts (Adam et al. 2004). The complete resection rate (R0+R1) may be increased with Cet addition, triplet chemotherapy, chronomodulated delivery (Chrono) and hepatic artery infusion (HAI) (Bouchahda et al. 2009; Kemeny et al. 2009; Garufi et al. 2010; Goere et al. 2010). Purpose: To increase the R0+R1 rate from 15% to 30% in pts with unresectable KRAS wt LM-CRC despite failure of 1-3 prior chemo protocols. Methods: 64 pts received iv Cet (500 mg/m²) and Chrono (18 pts) or conventional (Conv, 46 pts) HAI of Irinotecan (180 mg/m²), 5-Fluorouracil (2800 mg/m²), and Oxaliplatin (85 mg/m²) q2 weeks. Liver surgery was performed according to q6wks multidisciplinary meetings. Results: There were 22F and 42 M, aged 33-76 years, with good PS (0/1/2: 40/22/2). Liver lesions were bilateral in 50 pts (78.1%), with a median of 10 metastases (1-50) and largest diameter of 52 mm (15-172). Five courses (1-13) were given to 61 pts (3 never treated), as 3-4th line for 35 pts (54.6%). Grade 3-4 toxicities per pt were neutropenia (40%), abdominal pain (26%), fatigue (18%) and diarrhea (16%). Tumor response (RECIST) was achieved in 28 pts (2 CR, 26 PR), with an objective response rate of 46% [95%CL, 33-58]. Disease control rate was 95% [90-100]. The main endpoint was met, with R0-R1 resections in 19/61 pts, for an overall complete macroscopic resection rate of 28% [17-39]. R0+R1 resections were performed in 33.3% Chrono pts and 25.6% Conv pts, with worse initial prognosis for the Chrono pts (>6 segments involved, 50% vs 9%; > 9 metastases, 75% vs 27%). Median progression-free and overall survival were 8.7 months [6.9-10.5], and 25.7 months [14.2-37.2] respectively. Conclusions: The combination of intravenous Cet and triplet hepatic artery infusion safely doubled the expected rate of complete resections of LM-CRC, despite prior failure of systemic chemo. This most effective treatment option now deserves upfront testing. Clinical trial information: NCT00852228.
Dosimetric coverage of anal sphincter by 3D conformal fields in patients undergoing neoadjuvant chemoradiation for rectal cancer: An implication in the concept of sphincter-preserving radiation therapy.
Authors: Chen Yi-Jen , Chen Michelle B. , Liu Alan Jianan , Tsai Peter Tsung Wen , Liu An 
Published: February 2017

558 Background: Functional impact related to dosimetric coverage of the anal sphincter in rectal cancer patients treated with neoadjuvant chemoradiation (NCRT) remains unknown. We evaluated the anatomic location of the anal sphincter to pelvic bony landmarks related to 3D conformal radiotherapy (3DRT) and studied the dosimetric coverage of the anal sphincter in patients undergoing NCRT for rectal cancer. Methods: Between June 2006 and March 2012, 64 patients with rectal cancer treated with NCRT were included. All patients were treated in prone position on a bellyboard by 3DRT with 3 or 4-field setup up to 5,040 (86%) or 5,400 (14%) cGy. The inferior borders of the RT fields used were the lower of either at 3-5 cm inferior to the lowest gross tumorous volume (GTV) or at the inferior border of the obturator foramina (IBOF). The anal sphincters were contoured retrospectively and dose distributions were determined using dose volume histograms. Results: The mean anal sphincter volume was 5.1 cm3 (range, 1.3 – 11.2 cm3). On average, the center of anal sphincter was 18.6 mm inferior to the IBOF. In 53 cases (82.8%), the anal sphincter was completely inferior to the IBOF. In the remaining 11 cases (17.2%), the anal sphincter was either overlapping the IBOF (10 cases; 15.6%), or completely superior to the IBOF (1 case; 1.7%). On average, the center of anal sphincter was 39 mm inferior to the lowest edge of GTV. In 19 cases (30%), the anal sphincter was completely outside of the inferior border of the RT fields. In another 10 cases (16%), the sphincter was more than 4 cm away from the GTV inferior border but was partially treated. The mean dose delivered to anal sphincter was 2795 cGy (range, 245–5441 cGy). Lower mean doses delivered to the anal sphincters were noted for larger distances from the center of the anal sphincter to the GTV. Conclusions: Minimizing dose delivered to anal sphincter is possible, especially for upper or mid rectal cancer. However, meticulous planning to define the inferior border of RT fields is necessary. Future studies will focus on the correlation between RT dose distribution to the anal sphincter and anal-rectal dysfunction.