bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of panobinostat (LBH589) in patients (pts) with refractory metastatic colorectal cancer (MCRC).
Authors: Gold Philip Jordan , Smith David A. , Iriarte Desiree , Boatman Barry , Kaplan Henry G. 
Published: February 2017

582 Background: LBH589 is a novel histone deacetylase inhibitor (HDACi) which induces apoptosis of tumor cells. LBH589 has been shown to cause regression of colon cancer in animal models and phase I trials have shown the agent to be well tolerated, providing rationale for studying this agent in pts with MCRC. Methods: This was a multicenter, open-label phase II study of single agent LBH589 in patients with MCRC who failed at least 2 prior regimens for metastatic disease. Measurable disease, adequate organ function and ECOG performance status of 0-2 were required. Pts received LBH589 30mg po on M/W/F until disease progression. Pts were evaluated for toxicity every 2 weeks and for response every 8 weeks. The primary endpoint was overall survival. Secondary endpoints included response rate, time to progression (TTP), and toxicity. Results: 29 pts were enrolled (16 male, 13 female). The median age was 59 (range 41-76). The median number of prior treatment regimes was 3 (2-11). The median survival was 5.1 months (range 1-24+). There were no objective responses. 3 pts had SD at 8 weeks. The median TTP was 7.7 weeks (range 1-38.). Six pts had grade 4 thrombocytopenia requiring platelet transfusion. Nine pts required dose reductions for toxicity. Conclusions: Single-agent LBH589 was not associated with objective tumor responses in this heavily pre-treated pt population. However, the median survival was comparable to that seen in other trials of single agent targeted therapy in the treatment of refractory MCRC. Thrombocytopenia was significant, and may complicate potential trials of combination therapy.
Gender differences in outcomes for early-stage colon cancer.
Authors: Alipour Sina , Kennecke Hagen F. , Lim Howard John , Cheung Winson Y. 
Published: February 2017

605 Background: Retrospective analyses of clinical trials suggest that gender may influence the risk of recurrence and survival in patients diagnosed with early stage colon cancer. Whether this association persists in the setting of routine clinical practice is unclear. Our aims were to 1) assess for gender differences in outcomes in early stage colon cancer and 2) evaluate if the effect of gender on outcomes is modified by adjuvant therapy (AT). Methods: Using a population-based cohort of patients diagnosed with stage II or III colon cancer and referred to any 1 of 5 regional cancer centers in British Columbia, Canada from 2001 to 2005, we compared 5-year outcomes between men and women. Multivariate Cox proportional hazard models were constructed to explore the relationships between gender and prognosis, while controlling for patient and tumor characteristics. Interaction terms between gender and AT were used to examine the predictive value of gender. Results: We included 1837 patients: 970 men and 867 women. Baseline characteristics were similar: median ages were 68 and 69 years; 39 and 38% had stage II colon cancer; and 46 and 44% received AT, respectively. Outcomes were better in women than in men (5-year cancer-specific survival rate 73 vs. 71% and 5-year overall survival rate 68 vs. 62%). In Cox regression models, women continue to experience better overall prognosis (HR for death = 0.80, 95% CI 0.69-0.92, p=0.003) when compared to men. Advanced age, stage III disease, and lack of AT also correlated with worse outcomes (all p<0.01). The effect of gender on outcomes remained similar regardless of AT (HR 0.86 among women with AT and HR 0.75 among women without AT, interaction p=0.35). Conclusions: Gender is a prognostic, but not a predictive, factor for this cohort of patients with early stage colon cancer. Studies to investigate the biological mechanisms underlying this gender difference in outcomes are warranted.
Variation in gross tumor volume delineation using CT, MRI, and FDG-PET in planning radiotherapy of anal cancer.
Authors: Serup-Hansen Eva , Hendel Helle Westergren , Johannesen Helle Hjorth , Ottosson Wiviann , Hollensen Christian , Persson Gitte Fredberg , Geertsen Poul F. , Havsteen Hanne 
Published: February 2017

652 Background: Radiotherapy (RT) outcome depends on accurate delineation of gross tumor volume (GTV) regarding tumor size and position. CT and MRI are standard image modalities as they provide the necessary structural information. Positron emission tomography with flourodeoxyglucose (FDG-PET) visualizes glucose metabolism in active tumor tissue. The main objective was to explore the intra-observer and inter-modality variation of the GTV delineated on CT, MRI and PET images. Methods: Between November 2006 and July 2009, 22 patients with biopsy-proven anal carcinoma stage T1-T4/N0-3/M0-1 scheduled for curative RT were included in the study. All patients underwent FDG-PET/contrast enhanced CT and MRI. The delineations of GTV were done twice for each imaging modality with a minimum of 3 months in between. Delineations on the CT and MRI were done by routine methods. For the PET part three different cut-off values were used: SUV 2.5, 40% and 50% of maximum SUV. Non-overlap was calculated by subtracting the intersection from the union of two sets both regarding intra-observer variation and inter-modality variation. The GTV were compared for size, intra-observer variation and non-overlap using Wilcoxon rank sum test, where p < 0.05 was considered significant. Results: Volume size: the median GTV-CT was 25.6 cm3 which was significantly larger compared to GTV-MRI (7.2 cm3) and the GTV from the different PET cut offs (6.2 cm3, 10.6 cm3 and 7.0 cm3). Intra-observer variation: the median GTV delineated on CT, MRI and PET did not vary significant between delineation number 1 and 2. Non-overlap: the non-overlapping regions in GTV between delineation 1 and 2 using CT and MRI (20.5% and 22.5%) were significantly different from the PET cut offs (5.5% , 6.4% and 5.8%). Conclusions: Delineation of anal tumors is difficult; CT gives rise to the largest GTV with considerable intra-observer variation. MRI has the same degree of inaccuracy, but smaller GTV. PET-GTVs are the smallest with significant smaller intra-observer uncertainty.
Intensity-modulated radiation therapy (IMRT) with concurrent chemotherapy for anal cancer: A large single-institution experience.
Authors: Mitchell Melissa Pulfer , Abboud Mirna , Crane Christopher H. , Eng Cathy , Chang George J. , Rodriguez-Bigas Miguel A. , Skibber John Michael , You Y. Nancy , Beddar Sam , Krishnan Sunil , Delclos Marc E. , Das Prajnan 
Published: February 2017

661 Background: IMRT for squamous cell anal carcinoma enables sparing of normal tissues potentially leading to decreased toxicity. We evaluated toxicity, local control and survival in anal cancer patients treated with IMRT and concurrent chemotherapy. Methods: Between March 2007 and January 2011, 65 patients were treated at our institution with IMRT and concurrent chemotherapy for newly diagnosed, localized squamous cell carcinoma of the anal canal. Radiotherapy was delivered with a simultaneous integrated boost technique, with dose based on the T stage. The median total dose to the primary tumor was 54 Gy (range 50 – 58.8 Gy) and the median dose to the pelvis was 45 Gy (range 40.5-50.4 Gy) delivered in 25-29 fractions. The concurrent chemotherapy regimens were 5-fluorouracil (5-FU) and cisplatin (75%), capecitabine and oxaliplatin (11%), 5-FU and mitomycin C (MMC) (5%), cisplatin and MMC (2%), capecitabine and cisplatin (2%), capecitabine and MMC (2%), and 5-FU given alone due to other co morbidities (5%). Results: Median age at diagnosis was 57 years (range 35-80). The patient population was 71% female. The percentage of patients with stage I, II, IIIA, and IIIB disease were 12%, 28%, 14% and 42%, respectively. Stage was Tx in 5%. 8% of patients were HIV positive. Grade 3 gastrointestinal toxicity occurred in 9% and moist desquamation beyond the perianal area occurred in 17%. 91% of patients completed treatment without a break. The median follow-up was 19 months (range 1 to 49 months). The 2-year local control was 93%. Four patients had a local recurrence, of which two underwent salvage APR, one refused surgery, and one patient, who also had metastatic disease, received chemotherapy. Four patients developed metastasis. The 2 year distant control was 93%. There were two deaths due to the development of metastatic disease. The 2-year overall and disease-free survival were 96% and 89%, respectively. Conclusions: Concurrent IMRT and chemotherapy was well tolerated with low rates of acute toxicity, and excellent local control, disease-free survival and overall survival. Our results compare favorably with other published data despite a higher proportion of patients with advanced disease.
Clinical outcomes with high-dose image guided radiotherapy (IGRT) compared with non-IGRT for the treatment of clinically localized prostate cancer.
Authors: Zelefsky Michael J. , Kollmeier Marisa , Cox Brett Wayne , Pei Xin , Hunt Margie 
Published: February 2017

12 Background: To compare toxicity profiles and biochemical tumor control outcomes between patients treated with high-dose image-guided radiotherapy (IGRT) and high-dose intensity-modulated radiotherapy (IMRT) for clinically localized prostate cancer. Methods: 186 patients with prostate cancer were treated with IGRT to a dose of 86.4 Gy with daily correction of the target position based upon kilovoltage imaging of implanted prostatic fiducial markers. This group of patients was retrospectively compared with a similar cohort of 190 patients who were treated with IMRT to the same prescription dose without, implanted fiducial markers in place (non-IGRT). In both groups the margins used for the prostate were the same. The median follow-up time was 2.8 years (range, 2-4 years). Results: A significant reduction in late urinary toxicity was observed for IGRT patients compared with the non-IGRT patients. The 3-year likelihood of urinary toxicity for the IGRT and non-IGRT cohorts were 10.4% and 20.0%, respectively (p=0.02).Multivariate analysis identifying predictors for late urinary toxicity demonstrated that, in addition to the baseline IPSS, IGRT was associated with significantly less late urinary toxicity compared with non-IGRT. The incidence of late rectal toxicity was low for both treatment groups (1.0% and 1.6%, respectively; p = 0.81). No differences in prostate-specific antigen relapse–free survival outcomes were observed for low- and intermediate-risk patients when treated with IGRT and non-IGRT. For high-risk patients a significant improvement was observed at 3-years for patients treated with IGRT compared with non-IGRT. Conclusions: IGRT is associated with a reduction in late urinary toxicity and improvement in biochemical tumor control after definitive high-dose external beam radiotherapy compared with high-dose IMRT. These data suggest that, for definitive radiotherapy, the placement of fiducial markers and daily tracking of target positioning should be the preferred mode of external beam radiotherapy delivery for the treatment of prostate cancer.
A randomized phase II study of OGX-427 plus prednisone versus prednisone alone in patients with chemotherapy-naive metastatic castration-resistant prostate cancer.
Authors: Chi Kim N. , Hotte Sebastien J. , Ellard Susan , Gingerich Joel Roger , Joshua Anthony Michael , Kollmannsberger Christian K. , Yu Evan Y. , Gleave Martin Edwin 
Published: February 2017

121 Background: Heat Shock Protein 27 (Hsp27) is a stress-activated, multi-functional chaperone protein highly expressed in cancer that regulates cell signaling and survival pathways implicated in cancer progression. In prostate cancer models, Hsp27 complexes with androgen receptor (AR) and enhances transactivation of AR-regulated genes. OGX-427 is a 2nd generation antisense that inhibits Hsp27 expression with in vitro and in vivo efficacy. Phase I studies have demonstrated tolerability and single agent activity. Methods: Patients (pts) with CRPC, no/minimal symptoms and any prior treatment other than chemotherapy were randomized 1:1 to receive prednisone (P) 5 mg PO BID or P with OGX-427 600 mg IV x 3 loading doses followed by 1000 mg IV weekly. Primary endpoint was the proportion of pts progression free (PSAWG 2 criteria) at 12 weeks. A 2-stage MinMax design (H0 = 5%, HA >20%, α=0.1, β=0.1) will enrol 32 pts total per arm and provide 70% power to detect the difference at a 0.10 1-sided significance. Secondary endpoints include PSA decline, measurable disease response, and circulating tumour cell (CTC) enumeration. Results: In the first 22 pts randomized (11 to OGX-427+P, 11 to P), baseline median age was 71 years (53-86), ECOG PS 0 or 1 in 64% and 36% of pts, median PSA 89 (6-606), metastases in bone/lymph nodes/liver or lung in 77%/64%/10%, 23% had prior treatment with P, and 91% had ≥5 CTC/7.5 ml (median 18/7.5 ml). Thus far, 82% of pts randomized to OGX-427+P have had a PSA decline (55% with ≥30% decline) and 18% a PSA increase; 40% of pts treated with P have had a PSA decline (20% with ≥30% decline), 10% no change and 50% with PSA increase. CTC conversion from ≥5 to <5/7.5 ml has occurred in 60% of pts randomized to OGX-427+P and 20% of pts treated with P alone. Grade 1-2 infusion reactions (e.g., chills, diarrhea, flushing) have occurred in 45% of pts receiving OGX-427+P and 1 pt developed hemolytic uremic syndrome after week 7 probably related to OGX. Conclusions: Preliminary data provide clinical support for the role of Hsp27 in AR signalling and as a therapeutic target for prostate cancer. Enrolment on this study continues. Funded by a grant from the Terry Fox Research Institute.
Sick leave in patients with prostate cancer before, during, and after radiotherapy.
Authors: Sveistrup Joen , Meidahl Petersen Peter , Mortensen Ole Steen , Engelholm Svend Aage 
Published: February 2017

153 Background: Returning to work following cancer treatment is a sign of recovery. Side-effects might result in sick leave rendering patients unable to work. The purpose of this study was to determine the pattern of sick leave in patients with prostate cancer (PCa) before, during and after definitive radiotherapy. Methods: The Danish DREAM-database contains information on all social benefits paid out to Danish citizens. Based on the DREAM-database it is possible to assess whether a patient is working, on sick leave, or retired. Data on 427 of 473 Danish citizens, treated with definitive intensity-modulated radiotherapy for PCa at our center between January 1 2005 and May 1 2010, were obtained from the DREAM-database. Of the 427 patients 118 patients were working or available to the job market at the start of radiotherapy. Of the 118 patients 59 patients were on sick leave at some point during the course of radiotherapy and they followed in the DREAM-database from one year prior to radiotherapy until one year after the treatment. The median age was 60 (age, range 49–65). Based on the data from the database the 59 patients were divided into the four categories “Working or unemployed”, “Sick leave”, “Retirement” or “Dead”. Furthermore, the patients’ statuses after sick leave were determined. Results: The results are shown in the table. Nearly all patients (91.5%) return to work following sick leave. One year after radiotherapy 64.4% of the patients are working, and 13.6% are on sick leave. Conclusions: The vast majority of patients that are on sick leave during the course of radiotherapy for PCa return to work. However, one year after RT only 64 % are working or available for work indicating that the return to work for a lot of the patients is relatively short-lasting. Further research is needed to clarify why. [Table: see text]
Urinary exosomes as a stable source of mRNA for prostate cancer analysis.
Authors: Russo Leileata M. , Bate Kendall , Motamedinia Piruz , Salazar Guillermo , Scott Anna , Lipsky Michael , Sadeghi Neda , Lin James , Comper Wayne D. , Petrylak Daniel Peter , McKiernan James M. 
Published: February 2017

174 Background: Exosomes are novel lipid bilayer vesicles that are released into biofluids such as urine and carry high integrity RNA from the parent cell which they were derived. Due to their unique stability and the fact that they contain prostate specific mRNA transcripts, we examined their potential as a non-invasive source of mRNA biomarkers for prostate cancer analysis. Methods: Following a Columbia University approved IRB protocol, random urine samples were collected from 163 men who were stratified into 4 groups: biopsy negative (Bx Neg, n=39), biopsy positive (Bx Pos, n=47), post-radical prostatectomy (RP, n=37) and controls (males <35 yrs, n=40). Urine samples were stored at 4°C and 0.8 μm filtration was used to remove whole cells and debris. Urinary exosomal RNA was isolated using our in-house technique. RT-qPCR was used to analyze PSA, PCA3, androgen receptor (AR), survivin, NCOA2, RAD21, transmembrane protease serine 2 (TMPRSS2), ERG and TMPRSS2:ERG fusion at the mRNA level. Results: Mean serum PSA protein level and age were similar in the Bx Neg and Bx Pos groups. Relative quantitation (RQ) of genes standardized to the PSA gene revealed that ERG (P<0.005), PCA3 (P<0.005), TMPRSS2:ERG fusion (P<0.05), TMPRSS2 (P<0.05) and survivin (P<0.005) were significantly increased in the Bx Pos vs. Bx Neg group. TMPRSS2:ERG fusion events occurred in 68% of Bx Pos vs. 44% of Bx Neg patients and were present in only 5% of controls. No patient in the RP group had positive TMPRSS2:ERG detection; this finding was further supported by the loss of TMPRSS2:ERG expression for 4 Bx Pos patients following prostatectomy suggesting specificity of the fusion event to the prostate. Conclusions: This study confirms urinary exosomes as a source of high quality RNA and showed significant differences in the expression of ERG, PCA3, TMPRSS2:ERG genes between the Bx Pos and Bx Neg groups. Our findings are consistent with previous studies based on tissue and post-prostate massage urinary cell analyses. The unique stability and yield of urinary exosomal RNA collected without a prostatic massage will hopefully simplify sample handing, obviate sample variability and patient discomfort inherent to prostate massage, and broaden the role of exosomes in future diagnostic testing.
11C-choline PET scanning is more accurate than biopsy in assessment of localized prostate cancer planned for radical prostatectomy.
Authors: Davis Ian D. , Lee Sze Ting , Shanker Lekshmy , Clouston David , Bolton Damien M , Angus David , Webb David , Lawrentschuk Nathan , Woon Dixon Teck Sing , Esler Stephen , Lim Joon Daryl , Chang Joe , O'Sullivan Richard , Pathmaraj Kunthi , Tochon-Danguy Henri , O'Keefe Graeme Joseph , Scott Andrew Mark 
Published: February 2017

182 Background: A decision to treat prostate cancer (PC) with radical prostatectomy (RP) with curative intent requires confidence that the PC is confined to the prostate. PC outcomes will improve with better selection of surgical candidates. Current imaging modalities include CT and MRI but have limited accuracy. We assessed 18F-FDG (FDG) and 11C-choline (CHOL) PET in men planned for RP to determine the accuracy of PET, effects of PET on decision making by surgeons, and correlation with PSA. Methods: Written informed consent was obtained from eligible participants (pts) planned for RP. All men underwent TRUS-guided prostatic biopsies, CT and MRI scans, PSA and standard tests of organ function. The urologist then documented the treatment plan based on these results. Pts then underwent FDG and CHOL PET and the urologist then determined whether this information altered the treatment plan. After surgery the RP specimen was reconstructed, examined histologically and correlated with TRUS and imaging results on a sextant-based analysis (apex/mid/base on both sides). Results: 30 pts entered and completed the trial. Outcomes are shown in the table. Neither PET modality significantly affected decisions about surgery. Preoperative PSA did not correlate with degree of involvement. FDG PET was unhelpful. Conclusions: CHOL PET was the most sensitive and most accurate modality with highest congruity with pathology and had excellent positive predictive value, but was least specific. CHOL PET was superior to both TRUS biopsy and MRI. Supported by grant 487916 through Cancer Australia, Prostate Cancer Foundation Australia, Australian Government Department of Health and Aging. [Table: see text]
Effect of chronic treatment of combined statins and aspirin on the risk of prostate cancer detection.
Authors: Suarez Cristina , Morales Rafael , Placer Jose , Nunez Isaac , Planas Jacques , Valverde Claudia María , Ropero Jordi , Maldonado Xavier , Morote Juan , Carles Joan 
Published: February 2017

185 Background: The role of chronic treatment (ChT) with statins and aspirin on prostate cancer (PC) carcinogenesis is controversial. Both drugs are frequently used in adult men who are at risk of PC, and many of them receive both drugs simultaneously. The impact of the combined treatment (CT) with statins and aspirin on PC risk has never been reported. We proposed to explore the influence of ChT with statins and aspirin in the PC risk detection and their aggressiveness. Methods: 2408 men were consecutively biopsied for cause: PSA > 4 ng/mL (64.4%), abnormal DRE (9%) or both (26.6%). ChT with statins and aspirin (>1 year) was controlled. Median age was 68 years (46–86) and median PSA 7.0 ng/mL (0.7-1279). At least 10 cores, plus 1 to 8 additional cores, were obtained. The PC detection rate was 35.2% and the Gleason score was < 7 in 20.8%, 7 in 50.9% and > 7 (HGPC) in 28.3%. Multivariate and univariate analysis were done and OR calculated to analyze the strength of the relationships. Results: 440 men (18.3%) were receiving statins alone (SA), 160 (6.6%) aspirin alone (AA), and 304 (12.6%) both drugs simultaneously. Multivariate analysis showed that CT was the only independent predictor of a reduced risk of PC detection, p=0.025, (OR 0.589, 95%CI 0.370-0-936). PC was detected in 552 of 1502 men (36.7%) not receiving statins or aspirin, 34.5% (152/440) receiving SA, 40% (64/160) receiving AA, and in 26.3% (80/304) receiving statins and aspirin simultaneously. Related to cancer aggressiveness, multivariate analysis showed that combined treatment predicted significantly an increased risk of HGPC, p=0.013, (OR 2.672, 95%CI 1.226-5.825). HGPC was detected in 136 of 552 (24.6%) PCs detected in men not receiving statins or aspirin, in 40 of 152 (26.3%) PCs detected in men receiving SA, in 24 of 64 (37.7%) PCs detected in men receiving AA, and in 40 of 80 (50%) PCs detected in men receiving statins and aspirin simultaneously. Conclusions: This study suggests that ChT with the combination of statins and aspirin reduce significantly the risk of PC detection in men subjected to prostate biopsy for cause. However, this reduction of PC detection is accompanied by a significant increase of PC aggressiveness.