bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transient increase in serum CEA while on adjuvant chemotherapy for colon cancer: Is this of prognostic importance?
Authors: Mitchell Nicola Jane , Hinder Victoria , Murray Melissa , Macapagal Jerome , Thompson Paul Ivan , Sharples Katrina , Findlay Michael P. N. 
Published: February 2017

654 Background: Serum Carcinoembryonic Antigen (CEA) is used to monitor response to treatment in metastatic colon cancer. Transient surges in CEA can occur after initiation of chemotherapy and are not associated with worse outcome. There is little data on transient CEA surge in the adjuvant setting. We aimed to review patterns of change in CEA levels with adjuvant chemotherapy and investigate associations between transient rises and patient survival. Methods: A retrospective review of patients in Auckland with a new diagnosis of colon cancer in 2001 or 2005 was reported previously [Murray, NZMJ, 2011]. CEA results immediately pre-chemotherapy, during and up to 9 months post chemotherapy were collected and death data was updated. Increase in CEA during chemotherapy was measured as the maximum change from baseline; values more than 2 (within-person) standard deviations above baseline [Erden, Scand, J Clin Lab Inv, 2008] were classified as increased. An increase was transient if the last recorded CEA post chemotherapy was within 2 sd of baseline. Three patient groups were defined: NI (no increase in CEA); TI (transient increase in CEA); and CI (continuous increase in CEA). Kaplan-Meier methods were used to estimate 5-year survival; Cox regression and log-rank p-values were used to compare survival. Results: Of the 77 patients identified with stage II or III disease who had received adjuvant chemotherapy, 61 had sufficient CEA data to be included. The TI group were younger (median [quartiles]: TI 59 [54, 64]; NI 65 [53, 74]; CI 68 [62, 74]) but a greater proportion were stage II (TI 32%; NI 23%; CI 17%). Patients were followed up for a minimum of 7.3 years (or death). Number of deaths per group were: TI 3/19; NI 9/30; CI 7/12. The 5 year overall survival was: TI 95%; NI 83%; CI 42%. There was no significant difference between TI and NI (p = 0.1), but the confidence interval was wide (HR 0.3; 95% CI (0.07 to 1.5). For CI compared to NI, the HR was 2.8 (95% CI (1.0 to 7.6), p = 0.04). Conclusions: The observation that CEA surge does not signal poorer prognosis will be further examined as part of a separate population-based New Zealand-wide study of colorectal cancer diagnosis, treatment and outcome. Part funded by a Genesis Oncology Trust grant.
Radiosensitization by erlotinib and veliparib in esophageal squamous cell cancer.
Authors: Whitley Alexander , Cooper Tiffiny , Angajala Anusha , Trummell Hoa , Jackson Josh , Bonner James A. , Yang Eddy Shih-Hsin 
Published: February 2017

70 Background: Dysregulation of the HER/EGFR family is identified in esophageal cancers and confers resistance and inferior survival rates. In addition to their unique selectivity in killing DNA repair-deficient tumors, poly-ADP ribose polymerase inhibitors (PARPi) can enhance radiation-induced cytotoxicity. We and others have also previously demonstrated attenuation of DNA repair capacity in HER-inhibited cells to induce a contextual synthetic lethal interaction with PARPi. We thus hypothesized that erlotinib, a tyrosine kinase inhibitor directed against HER1/HER2, could induce a transient DNA repair deficit and subsequently increase DNA damage with the PARPi veliparib in esophageal cancer cells while increasing tumor radiation (RT) sensitivity. Methods: Esophageal SCC cell lines (KYSE-30, KYSE-410, and OE-21) were treated with combinations of vehicle, erlotinib, veliparib (a PARP1/2 inhibitor), and RT. DNA damage and repair and signaling proteins were assessed by immunofluorescence staining of cells for DNA damage and repair foci and/or western blot analysis. Cell viability and cytotoxicity were determined via cell proliferation assays and colony formation assays, respectively. Tumor growth delay was assessed in mice bearing esophageal tumor xenografts. Results: Consistent with our hypotheses, erlotinib increased γ-H2AX foci, a marker of DNA double strand breaks (DSBs), in all three esophageal SCC tumor cells. This coincided with reduced DSB-repair capacity as assessed via RAD51 foci and pDNA-PK. Triple combination with erlotinib, veliparib, and RT demonstrated enhanced cytotoxicity. A subsequent increase in Annexin positive cells was observed, indicative of activation of the apoptotic response. Importantly, the triple combination was most effective in suppressing the growth of esophageal tumor xenografts in vivo (2– to 5.5–fold lower tumor volume) relative to other treatment groups. Furthermore, we observed reductions in tumor volume from baseline with this triple combination in 3/6 mice. Conclusions: Thus, the combination of erlotinib, PARPi, and RT can be an innovative and effective treatment strategy to enhance the therapeutic ratio and improve outcomes in esophageal SCC cancer patients.
Factors associated with recurrence in lymph node-negative gastric adenocarcinoma: Results from the U.S. Gastric Cancer Collaborative.
Authors: Jin Linda X. , Squires Malcolm Hart , Poultsides George A. , Votanopoulos Konstantinos Ioannis , Weber Sharon M. , Bloomston Mark , Pawlik Timothy M. , Hawkins William G. , Linehan David , Strasberg Steven M. , Archer Alexandra W. , Cardona Kenneth , Cho Clifford Suhyun , Kooby David A. , Levine Edward Allen , Winslow Emily , Saunders Neil , Spolverato Gaya , Maithel Shishir Kumar , Fields Ryan C. ,   US Gastric Cancer Collaborative
Published: February 2017

80 Background: Lymph node (LN) status is a predictor of recurrence after gastrectomy for gastric adenocarcinoma. Clinicopathologic predictors of recurrence in patients with node-negative disease are less well established. Methods: Patients who underwent surgery with curative intent for gastric adenocarcinoma from between 2000-2012 from participating institutions of the U.S. Gastric Cancer Collaborative were analyzed. Patients who died within 30 days of surgery were excluded. Univariate (UV) and multivariate (MV) analysis of clinicopathologic factors was associated with recurrence was performed. Results: Nine-hundred sixty-five patients from seven institutions were included in the analysis. Three-hundred forty-five (36%) had LN- disease, of whom 63 (18%) had disease recurrence after a median follow-up of 24 months. The most common patterns of recurrence were: peritoneal alone (44%), liver (22%), or combined liver/peritoneal (9%). This distribution did not differ significantly from LN+ disease. UV analysis identified tumor size, linitis plastica, diffuse histology, poor differentiation, signet ring histology, T stage ≥3, perineural invasion, and lymphvascular invasion as risk factors for recurrence (Table). On MV analysis, T stage≥3 (OR 3.6, 95% CI=1.7-7.5) and poorly differentiated histology (OR 2.4, 95% CI=1.2-4.9) were independent predictors of recurrence. Conclusions: Despite the presence of negative lymph nodes, patients with T stage ≥3 and poorly differentiated histology are at high risk of recurrence after gastrectomy for adenocarcinoma of the stomach. These factors, along with other patient and treatment-related variables, may be used to select patients who may benefit from more aggressive adjuvant therapy and to guide subsequent monitoring for disease recurrence. [Table: see text]
Robotic-assisted Ivor-Lewis esophagectomy in the elderly patient.
Authors: Abbott Andrea M. , Strom Tobin Joel Crill , Saeed Nadia , Shridhar Ravi , Hoffe Sarah E. , Almhanna Khaldoun , Meredith Kenneth L. 
Published: February 2017

93 Background: Esophageal cancer continues to increase in incidence worldwide with the age of diagnosis continuing to move towards an older onset. Robotic assisted approaches to esophagectomy have demonstrated decreased complications and length of hospitalization (LOH). We sought to examine the impact of age on outcomes in patients undergoing robotic assisted esophagectomy (RAIL). Methods: From 2009-2013, we identified patients undergoing robotic assisted Ivor Lewis esophagectomy. Patients were then stratified according to 3 age groups. Cohort 1, age less then 50, cohort 2, age 50-70, and cohort 3 >70. Statistical comparisons between LOH, operative time (OT), estimated blood loss (EBL), adverse events (AE) and mortality were made with Kruskal-Wallis and Chi-square tests. Results: We identified 134 patients who underwent RAIL and found no statistically significant difference between the three cohorts for OT, LOH, days spent in intensive care, AE or mortality. There was a difference in EBL with higher median blood loss (150 cc) seen in cohort 1 (50-600cc) and 3 (50-400cc) compared to cohort 2 (100 cc, (25-400cc)), p < 0.01. The most common AE were arrhythmia and pneumonia but this was not significantly different between the cohorts. The overall AE rate was 10% (cohort 1), 21% (cohort 2), 34% (cohort 3), p=0.14. There were 4 leaks (p =0.38) and 2 deaths (p=0.90) in the entire cohort. A separate analysis was done to compare elderly (>70) to the non-elderly (<70). Median EBL was higher in the elderly cohort (100cc (25-600) vs 150cc (50-400), p <0.01). There was a trend towards longer LOH in the elderly (9 (4-35) vs 11 (6-38) days, p =0.06). AE and mortality were not significantly different, although there was a trend toward increased AE (19.8% vs 34%, p=0.07) in the elderly, with arrhythmia being the most common AE. Conclusions: RAIL is a safe surgical technique for use in an aging patient population. We demonstrated there was no increased risk of LOH, AE or death in the elderly patients compared to their younger cohort.
Updated analysis of HERBIS-1: A phase ll study of trastuzumab (T-mab) in combination with tri-weekly S-1 plus CDDP in HER2-positive advanced gastric cancer.
Authors: Gamoh Makio , Sugimoto Naotoshi , Miwa Hiroto , Tsuda Masahiro , Nishina Shinichi , Okuda Hiroyuki , Imamura Hiroshi , Matsuyama Jin , Shimokawa Toshio , Sakai Daisuke , Kurokawa Yukinori , Komatsu Yoshito , Tsujinaka Toshimasa , Ishioka Chikashi , Furukawa Hiroshi 
Published: February 2017

98 Background: The HERBIS study demonstrated the promising antitumor activity and manageable toxicities of S-1 plus cisplatin and T-mab (SPT) regimen in patients (pts) with HER2-positive advanced gastric cancer (AGC) (Sugimoto et al. ASCO GI 2012, Abstract 70). We report the updated time-to event analysis. Methods: Main eligibility criteria were gastric or esophagogastric junction adenocarcinoma, HER2-positive, unresectable or recurrent, measurable lesion, no history of chemotherapy or radiotherapy, ECOG PS of 0-1 and adequate organ function. Pts received S-1(80-120mg / day) on days 1-14, cisplatin 60 mg/m2on day 1 and T-mab 8 mg/ kg on day 1 (6 mg/ kg from 2nd course) repeated every 3 weeks until disease progression. Primary endpoint was response rate (RR) and secondary endpoints were overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF) and adverse events. The planned sample size was 50 pts. Results: A total of 56 pts were enrolled from July 2011 to May 2012. Two pts were ineligible and one patient did not receive any treatment. Therefore, the efficacy and safety analyses were conducted in the full analysis set of 53 pts. The confirmed response rate was 67.9% (95% CI: 53.7-80.1), and the disease control rate was 94.3% (95% CI: 84.3-98.9). Median OS was 16.0 months (95% CI: 13.3 - NaN), median PFS was 7.8 months (95% CI: 6.0 – 8.8) and median TTF was 5.7 months (95% CI: 4.2 - 7.1), respectively at the median follow-up time of 13.5 months. The main grade 3/4 adverse events were leukopenia 8%, neutropenia 36%, anemia 15%, increased creatinine 6%, hypoalbuminemia 9%, anorexia 23%, diarrhea 8% and vomiting 6%. Conclusions: SPT have promising antitumor activity and manageable toxicities in pts with HER2-positive AGC. Clinical trial information: UMIN000005739.
Effect of adjuvant and salvage radiotherapy after radical prostatectomy on urinary continence.
Authors: Adam Meike , Lanwehr Dominik , Wenzel Philipp , Graefen Markus , Michl Uwe , Huland Hartwig , Tennstedt Pierre , Becker Andreas , Schwarz Rudolf , Schlomm Thorsten 
Published: February 2017

100 Background: The clinical value of adjuvant (aRT) or salvage radiation (sRT) for patient treated with radical prostatectomy (RP) is currently controversially debated. In this study, we assessed the impact of aRT and sRT on long-term urinary continence. Methods: Overall, 15,901 patients who underwent RP in our center between 1992 and 2012 were analyzed. aRT within the first 6 months was performed in 734 (2.9%) patients, and sRT after 6 months in 1405 (8.8%) patients (median time 21.6 months), respectively. Continence rates were assessed annually after RP using a self-administrated questionnaire. Median follow-up was 48.4 months. Continence was defined as the use of no pads or one safety pad. Incontinence was categorized by the number of used pads. The impact of additional radiation therapy on continence results was analyzed by logistic regression analyses, the chi2-likelyhood test and propensity score matching. Results: In multivariate logistic regression analysis, adjusted for age, prostate volume, extend of nerve-sparing, year of surgery, the event of additive RT (OR=1.2, p=0.17) was not statistically relevant correlated with the long-term continence status whereas all other variables significantly correlated with urinary incontinence (p<0.01, each). The lacking correlation of RT and continence remained in a second logistic regression model, adjusted for tumor features (pT, pN, Gleason, PSA, margin-status). The timing of RT (aRT vs. sRT) was not statistically relevant correlated with the long-term continence status (OR=1.7, p=0.09; OR=1.2, p=0.5) In addition, a comparison of all patients received aRT with a propensity score based matched cohort of RP only patients (corrected for age, prostate volume, extend of nerve-sparing and year of surgery) revealed no statistical significant impact of RT on continence (p>0.05). In 248 patients, the continence status was available pre and post RT, again not showing a negative impact of RT (p>0.05). Conclusions: Additive radiation therapy after radical prostatectomy does not negatively affect urinary continence.
Comparison of FRAX score to bone mineral density for estimating fracture risk in patients with CRPC on androgen-deprivation therapy (ADT).
Authors: Bienz Marc Nicolas , James Herbert , Aleksic Ilija , Pieczonka Christopher Michael , Albala David , Iannotta Peter , Alom Modar , Mariados Neil , Mouraviev Vladimir , Saad Fred 
Published: February 2017

101 Background: A FRAX algorithm has been elaborated to estimate the ten-year hip fracture risk associated with this under-diagnosed condition. We aim to evaluate the fracture risk of patients who would otherwise be left untreated by the conventional T-score. Methods: Clinical data from 613 PCa patients undergoing ADT was collected from our AMP large urology group. Fracture risk was assessed using the country specific (USA) Fracture Risk Assessment Tool (FRAX). Also, a subset of patients (n=94) had received Dual-energy X-ray Absorptiometry (DXA). We compared the proportion of patients suitable for treatment according to the threshold of the FRAX fracture risk calculated with the BMD (>3%) and the T-score (<-2.5). Results: According to the FRAX algorithm (without BMD), 61.6% of our cohort require treatment. The FRAX score (with BMD) identified 46.8% of patients who had DXA suitable for treatment, in contrast to 19.1% by the T-score alone. Correlations were calculated between the various methods (Table). Conclusions: Our results demonstrate that many patients unidentified for treatment by the conventional T-score are at significant risk for fracture according to the FRAX algorithm with BMD. When calculated without the BMD, an even greater proportion of patients is found to be at risk and suitable for treatment. [Table: see text]
One-step ultrasound-based high dose rate (HDR) prostate brachytherapy with dose escalation to the dominant intra-prostatic lesion.
Authors: Crook Juanita M. , Ots Ana , Parker Brent , Schmid Matt , Batchelar Deidre , Araujo Cynthia , Hilts Michelle , Bachand Francois 
Published: February 2017

106 Background: To demonstrate feasibility of using high dose rate (HDR) brachytherapy to deliver 25% higher than prescription dose to the dominant intra-prostatic lesion (DIL) as defined on multi-parametric MRI for intermediate and high risk prostate cancer. Methods: Twenty six patients with predominantly unilateral disease consented to a University Ethics-approved phase II study of selective dose escalation. HDR brachytherapy was performed in weeks 1 and 3 of treatment, each delivering one fraction of 10 Gy to the whole prostate. External beam consisted of 46Gy/23 fractions starting 3 days after the first HDR fraction.T2 FSE images were obtained using 1.5T endorectal MRI in transverse, sagittal and coronal planes followed by Dynamic Contrast Enhancement after injection of gadolinium. Apparent Diffusion Coefficient maps were calculated. The DIL was contoured on the MRI and, following image registration, transposed to the preoperative TRUS performed in the treatment position. Intra-operative TRUS with source-delivery catheters in place was fused to the pre-op TRUS with the transposed DIL. The DIL was included in dose optimization criteria. Results: Twenty five of 26 patients had a visible DIL. Mean prostate percentage receiving the prescription dose (V100) was 98.2% (SD:1.1). Mean dose to 90% of the DIL (D90) was 13.2 Gy (SD: 1.7). DIL mean volume was 2.9 cc (SD:1.8) representing 9.5% (SD: 7.6) of the prostate volume. Coverage of the DIL was excellent with a median of 97% receiving the planned escalation of 25%. Established dose constraints to rectum and urethra were respected in all cases. The factor that limited DIL coverage was proximity to organs at risk. Peri-urethral location of the DIL limited coverage in five cases and two had a posterior DIL such that dose to the rectum limited escalation. However, these seven cases still achieved a mean DIL D90 of 12.2 Gy. Conclusions: Dose manipulation using US-planned HDR brachytherapy is readily achievable within the practice setting of a community cancer center. Dose escalation to the DIL to a mean of 132% of the prescribed dose for selected intermediate and high risk prostate cancer patients is feasible while respecting critical organ constraints. Further escalation is planned. Clinical trial information: NCT01605097.
Androgen receptor independent acquired mechanisms of resistance to enzalutamide in castration-resistant prostate cancer.
Authors: Szmulewitz Russell Zelig , Kregel Steve , Isikbay Masis , Cai Yi , Chen James Lin , Vander Griend Donald J 
Published: February 2017

129 Background: Enzalutamide (MDV3100) is a second generation androgen receptor (AR) antagonist with potent activity in the treatment of castration resistant prostate cancer (CRPC). However, most patients develop resistance and progression of disease; thus there is a critical need to identify novel targetable pathways mechanistically linked to this resistance. Methods: A panel of four prostate cancer cell lines (LAPC-4, LNCaP, VCaP, and CWRR1) was created each with a different AR status that are resistant to MDV3100 by culturing cells long-term less than 6 months in the drug at pharmacologic levels. The MDV3100 resistant (MDV-R) lines were assayed for proliferation, viability, resistance to docetaxel, and tumor take of subcutaneous xenografts. AR expression and ligand binding domain (LBD) DNA sequences were analyzed. Gene expression microarray comparison of resistant and non-resistant parental cell lines was performed. Prostate-specific antigen (PSA) and testosterone levels were analyzed from conditioned media. Results: Cell lines demonstrated heterogeneous growth characteristics.In vivo studies depicted increased or unaltered tumor take and growth in castrate athymic mice. In some cell lines growth was increased in vitro when drug was withdrawn; yet this growth was inhibited by physiological testosterone levels, both in vitro and in vivo. MDV-R cells remained sensitive to docetaxel in vitro and had increased levels of ARmRNA. However, total AR protein levels were lower or unchanged than the parental lines, with evidence for increased truncated forms of AR. The AR LBD acquired no new mutations. Secreted PSA was lower in all but one MDV-R line. Gene expression analyses demonstrated strong upregulation of IGFBP3 in all MDV-R cells. Pathway analysis implicated increased IGF and JAK/STAT signaling whereas mammalian target of rapamycin (mTOR) signaling was decreased. Conclusions: Although AR-mediated pathways contribute to enzalutamide resistance, a broader approach across several cell lines suggests that there may be even a greater contribution from pleiotropic, non-AR mediated mechanisms. Such mechanisms may include IGF signaling, JAK/STAT signaling and modulation of mTOR.
Identification of biologic and inflammatory markers for predicting clinical responses to sipuleucel-T in CRPC.
Authors: Hepgur Mehmet Faith , Dorff Tanya B. , Brining Lucy , Cai Jie , Pinski Jacek K. , Reed Mary , Luther Michael , Chan Betty , Quinn David I. 
Published: February 2017

134 Background: Sip-T prolongs OS in asymptomatic or minimally symptomatic CRPC. We prospectively evaluated biomarkers in men receiving Sip-T to identify predictors of SDP and OS. Methods: Circulating tumor cells (CTC), PSA, prostatic acid phosphatase (PAP), albumin (Alb), hemoglobin (Hb), serum alkaline phosphatase (SAP), LDH, C-reactive protein (CRP) and β2-microglobulin (β2m) were evaluated in a reference lab. SipT product parameters, CD54, CD54 upregulation (UPREG) and total nucleated cells (TNC) were measured by Dendreon. Survival was evaluated using Kaplan-Meier estimates; univariate Cox regression was used to investigate the effect of biomarkers on SDP and OS using 2-sided tests and corrected for multiple comparisons. Results: 92 men who received Sip-T were included. Median age was 69 (48-90). The median follow-up was 14 (1.3 –34.7) mos, and 33% of men had died. 21 men developed SDP at a median of 5.7 (1-19) mos. Univariate analyses of biomarkers and product parameters are shown in the table. In multivariate analysis independent risks factors were LDH (p=.04) and β2m (p=.004) for SDP; LDH (p=.04), PSA (p=.012), age (p=.012) and UPREG (p=.006) for OS. Conclusions: CTC, CRP, LDH are associated with outcomes after Sip-T, similar to findings with hormone or cytotoxic therapy. Correlation of improved OS with low PSA and higher Hgb, albumin and Sip-T immune parameters supports the hypothesis that SipT is more effective with low disease burden. Prediction of early disease progression by β2m and LDH warrants further study. [Table: see text]