bluuebunny/crossref_metadata_2025_split huggingface dataset:
Total bilirubin as a predictive marker for irinotecan-induced toxicity in patients with gastrointestinal cancer.
Authors: Makihara Katsuya , Azuma Sayaka , Hasegawa Hiroko , Ikeda Masataka , Fujitani Kazumasa , Mishima Hideyuki , Tsujinaka Toshimasa 
Published: February 2017

68 Background: Irinotecan (CPT-11) is widely used for the treatment of patients with gastrointestinal cancer. However, CPT-11 can cause severe neutropenia and diarrhea.It has been reported that the AUC of SN-38, an active metabolite of CPT-11, correlated with Pre-treatment serum total bilirubin level (PTB), but there is no criteria of dose setting based on the PTB. Therefore, we retrospectively searched the PTB which can serve as an indicator for dose setting of CPT-11. Methods: We investigated the incidence of neutropenia and diarrhea at the first 28 days in patients with gastrointestinal cancer who were administered CPT-11 alone in Osaka National Hospital from June 2006 to July 2013. Correlation between PTB and grade 3-4 neutropenia or diarrhea were assessed. When toxicity of correlation exists, ROC (receiver operating characteristic) analysis was conducted to explore the cut-off value of the PTB. In addition, the incidence of febrile neutropenia (FN) in the cut-off value was compared. Results: 87 patients were analyzed. Of these, 65 were gastric cancer, 22 were colorectal cancer. Although PTB was significantly higher in patients who experienced grade 3-4 neutropenia than those who didn’t (p<0.001), PTB was not associated with grade 3-4 diarrhea. As the results of ROC analysis, cut-off value of PTB associated with grade 3-4 neutropenia was determined to 0.8 mg/dL. The incidence of FN was significantly higher in 20% of patients with PTB ≥ 0.8 mg/dL compared with 1.6% of patients with PTB < 0.8 mg/dL (OR: 15.5, p=0.01). On the other hand, in subgroup analysis showed no difference in the incidence of FN and neutropenia in patients whose dose was less than 100 mg/m². Conclusions: PTB was a predictive marker for CPT-11-induced severe neutropenia and FN. Results of this study suggested needs of dose reduction to less than 100 mg/m2 in patients with PTB ≥ 0.8mg/dL.
Monte Carlo (MC)-based volumetric modulated arc therapy (VMAT) in locally advanced esophageal cancer with potential for dose escalation.
Authors: Hasan Shaakir , Sethi Anil , Breunig Jennifer , Axelrud Gabriel , Small William , Thomas Tarita 
Published: February 2017

77 Background: Previous attempts at dose escalation in esophagus radiotherapy (RT), mostly based on older planning techniques, have not shown improved outcomes. We aimed to investigate the importance of newer, sophisticated dose algorithms and treatment techniques in escalating target dose and reducing dose to organs at risk (OAR). Methods: Treatment plans for 10 patients were retrospectively evaluated using 3D conformal radiotherapy (3DCRT), MC based intensity modulated radiotherapy (IMRT), and VMAT. Prescription dose was 45 Gy to the planning target volume (PTV) in 25 fractions followed by a 5.4 Gy boost in 3 fractions. PTV (mean±s.d. = 681±236 cc) were planned with BrainLab iPlan 4.1 software as IMRT and VMAT. Dose distributions were calculated with both pencil beam (PB) and MC algorithms. Each PTV was normalized to receive at least 95% of 50.4 Gy or 60 Gy dose. OARs were evaluated as per RTOG1010 dose guidelines. Paired t-tests were used for statistical analysis. Results: IMRT vs. 3DCRT PTV 50.4 Gy: IMRT plans decreased heart and lung average Dmean by 4.7 Gy (p = 0.053) and 1.9 Gy (p = 0.001) respectively when compared to 3DCRT. In addition, average values of lung V5, V10, and V30 also reduced by 7.1%, 5.5%, and 3.6% respectively (p < 0.05). There was a 12.1% decrease in heart V40 (p=0.053) and 3.7% reduction in liver V30 (p=0.08). PTV 60Gy: IMRT plans at 60 Gy led to lower OAR doses compared to 3DCRT at 50.4 Gy. MC based IMRT results did not significantly differ from PB, with the exception of lung V5 which was 4.4% higher (p <0.001). VMAT vs. IMRT PTV 50.4 Gy: VMAT based planning, compared to IMRT, lowered V20 (3.4%, p=0.029), V30 (1.6%, p = 0.013), and spinal cord Dmax (5.4 Gy, p = 0.001). However, lung Dmean, V5, and V10 increased by 1.2 Gy, 11.7%, 16.7% respectively (p < 0.001). PTV 60 Gy: With VMAT planning, all OAR dose parameters were within the RTOG 1010 limits, although lung V5 and V10 exceeded acceptable limits by 1.6% and 2.6% respectively. Conclusions: Compared to 3DCRT, target dose escalation with IMRT and VMAT is possible with improved OAR dose sparing, as evaluated with MC algorithms. Increased dose values for V5 and V10 as seen in MC based VMAT plans call for reassessment of RTOG 1010 guidelines.
Impact of external-beam radiation therapy on outcomes among patients with resected gastric cancer: A multi-institutional analysis.
Authors: Ejaz Aslam , Spolverato Gaya , Kim Yuhree , Squires Malcolm Hart , Weber Sharon M. , Poultsides George A. , Votanopoulos Konstantinos Ioannis , Bloomston Mark , Fields Ryan C. , Kooby David A. , Acher Alexandra W. , Worhunsky David J. , Swords Doug S. , Saunders Neil , Jin Linda X. , Cho Clifford Suhyun , Schmidt Carl Richard , Herman Joseph M. , Maithel Shishir Kumar , Pawlik Timothy M. ,   US Gastric Cancer Collaborative
Published: February 2017

84 Background: Use of perioperative chemotherapy (CTx) alone versus chemo-radiation therapy (cXRT) in the treatment of resectable gastric cancer remains varied. We sought to define the utilization and effect of CTx alone versus cXRT on patients having undergone curative-intent resection for gastric cancer. Methods: Using the multi-institutional U.S. Gastric Cancer Collaborative database, we identified 505 patients between 2000 and 2012 with gastric cancer who received perioperative therapy in addition to curative-intent resection. The impact of perioperative therapy on survival was analyzed by the use of propensity-score matching of clinicopathologic factors among patients who received CTx alone versus cXRT. Results: Median patient age was 62 years and the majority of patients were male (58%). Surgical resection involved either partial gastrectomy (54%) or total gastrectomy (46%). On pathology, median tumor size was 5.0 cm; most patients had a T3 (37%) or T4 (36%) lesion and lymph node metastasis (74%). Margin status was R0 in most patients (89%). 211 (42%) patients received perioperative CTx alone whereas the remaining 294 (58%) patients received 5-FU based cXRT. Factors associated with receipt of cXRT were younger age (OR 0.98), T3 tumors (OR 1.52), and lymph node metastasis (OR 2.03) (all P < .05). Recurrence occurred in 214 (39%) patients. At a median follow-up of 28 months, median overall survival (OS) was 33.4 months and 5-year survival was 36.7%. Factors associated with worse OS included tumor size (HR 1.1), T-stage (HR 1.5), and lymph node metastasis (HR 1.58) (all P<0.05). In contrast, receipt of cXRT was associated with improved long-term OS (CTx alone: 21 months vs. cXRT 45 months; p<0.001). In the propensity-matched multivariate model that adjusted for tumor size, T-stage, and nodal status, cXRT remained associated with an improved long-term disease-free (HR 0.43) and overall (HR 0.41) survival (both P<0.001). Conclusions: XRT was utilized in 58% of patients undergoing curative-intent resection for gastric cancer. Using propensity-matched analysis, cXRT was an independent factor associated with improved recurrence-free and overall survival.
Open versus minimally invasive management of gastric GIST: An international multi-institutional analysis of short- and long-term outcomes.
Authors: Bischof Danielle Anna , Kim Yuhree , Blazer Dan G. , Maithel Shishir Kumar , Gamblin T. Clark , Bauer Todd W. , Karanicolas Paul Jack , Law Calvin , Quereshy Fayez A. , Pawlik Timothy M. 
Published: February 2017

85 Background: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the GI tract. Overall surgical experience with minimally invasive surgery (MIS) has increased, however, published reports on MIS resection of GIST are currently limited to small, single institution experiences. Methods: 397 patients who underwent surgical resection of a gastric GIST between 1998 and 2012 were identified from an international, multi-center database. The impact of the MIS approach on recurrence and survival was analyzed by the use of propensity-score matching by comparing clinicopathologic factors between patients who underwent open vs MIS resection. Results: Median patient age was 65 years and 50% were female. Median tumor size was 4.3cm (IQR 3.0-7.6cm). A minority of patients received neoadjuvant therapy (6%). Overall, 186 (47%) patients had a MIS approach: laparoscopic (89%), laparoscopic hand assist (4%), combined laparo-endoscopic (3%) and robotic (4%). There were 19 (10%) conversions to open; the most common reasons for conversion were tumor more extensive than anticipated (26%) and unclear anatomy (16%). Patients who underwent MIS resections had smaller tumors (MIS: 3.5cm vs open: 5.8cm; p<0.01). MIS resections were associated with minimal blood loss (MIS: 50 cc vs open: 225 cc) and shorter operative time (MIS: 160 min vs open: 201 min) (both p<0.01). There was no difference in rates of tumor rupture (MIS: 1.1% vs open: 0.9%; p=0.81). An R0 resection was achieved in the majority of patients (MIS: 98% vs open: 92%; p=0.07). MIS patients had a lower incidence of grade 3 or 4 complications (MIS: 3% vs open: 10%; p=0.01) and a shorter length of stay (MIS: 3d vs open: 8d; p<0.01). After propensity score matching for age, sex, tumor size, mitotic rate and tumor rupture, there was no difference in risk of recurrence or overall survival for the MIS treated group vs. the open group (HR 0.65 & HR 0.76, respectively; both p>0.05). Conclusions: An MIS approach for gastric GIST is associated with a low incidence of complications and a comparable R0 resection rate. The long-term oncological outcome following MIS is excellent and therefore the MIS approach should be considered preferable.
Clinical parameters’ model for predicting distant metastasis (DM) following definitive therapy in patients with localized esophageal and esophagogastric junction (E-EGJ) cancer.
Authors: Sudo Kazuki , Wang Xuemei , Wadhwa Roopma , Shiozaki Hironori , Hofstetter Wayne Lewis , Rice David C. , Lee Jeffrey H. , Bhutani Manoop S. , Weston Brian , Skinner Heath D. , Komaki Ritsuko , Maru Dipen M. , Blum Mariela A. , Ajani Jaffer A. 
Published: February 2017

89 Background: For localized E-EGJ cancer patients, chemoradiation followed by surgery (trimodality therapy [TMT]) or definitive chemoradiation (bimodality therapy [BMT]) are considered the standard of care. However, ˜30-40 % of patients with localized E-EGJ cancer develop DM. We hypothesized that a clinical parameters’ model can be established to predict DM. Methods: We analyzed E-EGJ cancer patients who completed TMT or BMT from our prospectively maintained database. Logistic regression models were used for analysis. Overall survival (OS) was estimated by the Kaplan-Meier method. We used the AJCC 6th edition. Results: Between 2002 and 2013, 356 TMT patients and 273 BMT patients were analyzed. 33% (119/356) of TMT patients and 40% (109/273) of BMT developed DM as a first relapse. The median OS from DM were 10.2 months (95% CI: 7.8-12.7) for TMT patients and 7.8 months (95% CI: 5.7-9.9) for BMT patients. In a logistic regression analysis for all patients, the following parameters were associated with a significantly increased risk of DM: age (odds ratio [OR]: 0.97 [95% CI: 0.96-0.99]), initial standardized uptake value (iSUV) of PET (OR: 1.02 [95% CI: 1.00-1.04]), Stage III/IVa (vs. I/II) (OR: 2.43 [95% CI 1.65-3.57]) and male (vs. female) (OR 3.99 [95% CI: 1.89-8.42]). For TMT patients, baseline T3/T4 (vs. T1/T2) (OR 2.75 [95%CI 1.10-6.86]), baseline N1 (vs. N0) (OR: 1.69 [95% CI: 1.03-2.77]), and poorly differentiated cancer (vs. well/moderately differentiated) (OR 1.78 [95% CI: 1.13-2.82]) were significantly associated with DM. Conclusions: Our data suggest that younger men with Stage III/IVa cancer and high iSUV are at risk for DM irrespective of local therapy (TMT or BMT). A nomogram to predict DM will be developed with a larger cohort. Supported by UT M. D. Anderson Cancer Center Multidisciplinary Research Grants, CA138671, CA172741, CA129926 from NCI (JAA) and Generous Donors.
Analysis of KRAS/NRAS mutations in phase 3 study 20050181 of panitumumab (pmab) plus FOLFIRI versus FOLFIRI for second-line treatment (tx) of metastatic colorectal cancer (mCRC).
Authors: Peeters Marc , Oliner Kelly S. , Price Timothy Jay , Cervantes Andres , Sobrero Alberto F. , Ducreux Michel , Hotko Yevhen , Andre Thierry , Chan Emily , Lordick Florian , Punt Cornelis J. A. , Strickland Andrew , Wilson Gregory , Ciuleanu Tudor-Eliade , Roman Laslo , Van Cutsem Eric , Tian Ying , Jung Andre Scott , Sidhu Roger , Patterson Scott D. 
Published: February 2017

LBA387 Background: Previously, this study showed significant improvement in progression-free survival (PFS) in pmab + FOLFIRI vs FOLFIRI (HR=0.73; 95% CI: 0.59-0.90; p=0.004) and a trend toward improved overall survival (OS; HR=0.85; 95% CI: 0.70-1.04; P=0.12; Peeters et al. JCO 2010). Recently, analysis from 1st-line mCRC PRIME study showed that mutations in RAS genes (KRAS/NRAS exons 2/3/4) predicted a lack of response to pmab (Douillard et al. NEJM 2013). Methods: The primary objective was to assess the tx effect of pmab + FOLFIRI vs FOLFIRI on OS and PFS based on RAS mutation status in the primary analysis population. Bidirectional Sanger sequencing was used to detect mutations in KRAS exons 3, 4 and NRAS exons 2, 3, 4 in patients (pts) with known WT KRAS exon 2 mCRC. Results: In this prospective retrospective analysis, overall RAS ascertainment rate was 85% (n=1008/1186). 18% of the WT KRAS exon 2 pts harbored additional RAS mutations (n=107/597). Efficacy is shown (Table). Tx HR for pts with WT RAS was 0.803 (95% CI: 0.629-1.024; P=0.077) for OS and 0.695 (95% CI: 0.536-0.903; P=0.006) for PFS. Conclusions: Improvements were observed in the tx effect of pmab + FOLFIRI vs FOLFIRI on OS and PFS in the WT RAS group vs the WT KRAS exon 2 group. Pts with MT RAS mCRC are unlikely to benefit by the addition of pmab to FOLFIRI, similar to pts with MT KRAS exon 2 mCRC in this study. These findings are consistent with previously reported outcomes by RAS status and support RAS testing to determine potentially appropriate pts for pmab tx. Clinical trial information: NCT00339183. [Table: see text]
Utility of multiparametric MRI at 3 tesla and MRI/ultrasound fusion-guided biopsy in detecting seminal vesicle invasion by prostate cancer.
Authors: Raskolnikov Dima , Rais-Bahrami Soroush , George Arvin , Turkbey Baris , Okoro Chinonyerem , Rothwax Jason , Shakir Nabeel , Walton-Diaz Annerleim , Siddiqui Minhaj , Su Daniel , Stamatakis Lambros , Wood Bradford J. , Choyke Peter L. , Pinto Peter A. 
Published: February 2017

128 Background: We aim to evaluate the correlation between multiparametric prostate MRI (MP-MRI) suspicion for seminal vesicle invasion (SVI) and pathology on MRI/US fusion-guided biopsy, as well as radical prostatectomy (RP). Methods: 822 patients underwent MP-MRI and MRI/US fusion-guided biopsy. 24 patients underwent targeted seminal vesicle biopsies. 5 patients had MRI findings suspicious for bilateral SVI, for a total of 29 lesions. MP-MRI targets were scored as low, moderate, or high suspicion for PCa involvement according to the validated NIH scoring system. Patient demographics were reviewed and positive predictive values (PPVs) of pre-biopsy suspicion levels were calculated with respect to correlative biopsy pathology and final RP pathology. Results: At the time of MP-MRI, the median age was 64 years with a median PSA of 10.74 ng/ml (Table). Thirteen (54.2%) had not been previously diagnosed with PCa. Of the 29 SV lesions on imaging, MP-MRI suspicions of low, moderate, and high were assigned to 3, 18, and 8 lesions, respectively. The PPVs of these MRI suspicion levels, confirmed by MRI/US fusion biopsy, were 0%, 77.7%, and 62.5%, respectively. The 3 patients in the low suspicion cohort all underwent RP, confirming targeted biopsy findings. Of those with moderate or high suspicion of SVI on MP-MRI, only 5 underwent RP, with a targeted biopsy accuracy of 80%. The overall accuracy of targeted SV biopsy was 87.5% (7/8) on final RP pathology. Conclusions: MP-MRI suspicion of SVI correlates highly with findings on targeted SV biopsy and final RP pathology, thus potentially playing a vital role in future preoperative staging for PCa. [Table: see text]
Impact of screening and treatment on racial and ethnic differences in health service use, cost, and mortality among advanced (T3 or greater) prostate cancer patients.
Authors: Malkowicz S. Bruce , Chhatre Sumedha , Schwartz Sanford , Jayadevappa Ravishankar 
Published: February 2017

131 Background: Limited information is available regarding the association between race/ethnicity, health service use, cost, and mortality in older patients with advanced (T3 or greater) stage prostate cancer. The objective is to analyze the race/ethnic differences in mortality, cost, and assess the mediating effect of prostate cancer screening and treatment on these differences in fee-for-service Medicare patients with advanced prostate cancer Methods: Retrospective, observational, case-control study using SEER-Medicare linked data. Cohort consisted of 15,054 elderly men diagnosed with advanced stage prostate cancer between 2001and 2004 and followed retrospectively for up to 2009. Cancer-free controls from Medicare data were used to determine the incremental cost of advanced stage prostate cancer. Racial/ethnic variation in health service use, cost, and mortality were analyzed using Poisson, GLM log-link, and Cox regression models. Results: For the age 66 to 75 and 76 to 85, age groups, racial/ethnic differences in health service use, cost, and all cause mortality were observed. Blacks were less likely to have received prostate cancer screening in the year prior to diagnosis of advanced prostate cancer, less likely to have received any treatment after diagnosis and had higher disease specific mortality. After adjusting for prostate cancer screening and treatment across age groups however, odds of prostate cancer-specific mortality were comparable between racial/ethnic groups suggesting that screening may have some mitigating effect on outcomes in the AA population HR 1.23 (1.07-1.41) versus HR 1.12(0.98-1.29). Conclusions: The pattern of racial/ethnic disparity varies by age group with higher mortality among black men. This may be attributable to disparity in prostate cancer screening or treatment. This suggests that the lack of consideration for racial considerations in the U.S. Preventive Services Task Force PSA recommendations could have disparate racial impact.
Molecular characterization of circulating tumor cells (CTC) and CTC subpopulations in progressive metastatic castration resistant prostate cancer (mCRPC).
Authors: Dittamore Ryan , Louw Jessica , Krupa Rachel , Anand Aseem , Danila Daniel Costin , Arslan Zaina , Bales Natalee , Marrinucci Dena , Scher Howard I. 
Published: February 2017

132 Background: Numerous resistance mechanisms have been postulated in progressive mCRPC. Determining the presence of putative predictive biomarkers in patients requires a real-time tumor assessment because the biology changes under the influence of the specific therapy(ies) that a patient (Pt) has received. We examined CTC and CTC subpopulation incidence and molecular characterization of tumors from Pts with progressive mCRPC to assess if determinants of resistance can be assessed through a CTC test. Methods: 48 samples from 21 unique progressive mCRPC pts treated with androgen receptor targeted (AR tx) therapies, 9 (43%) on Abiraterone plus Prednisone (AA+P) and 12 (57%) on Enzalutamide (E). Samples were collected and shipped to Epic Sciences, where cells were stained and CTC identified by fluorescent scanners and algorithmic analysis. CTCs, defined as classic (CK+ CD45- w/intact DAPI nuclei and distinct), apopotic (CK+, CD45-, non-intact nuclei) and CK- (CK-, CD45-, intact and distinct) were identified. CTCs reported per mL of blood and were examined for AR, PTEN & ERG. CTC data were analyzed in context of PSA, Veridex CTC (reported per 7.5mL of blood), and clinical history. Results: With Epic, all 21 pts had detectable CTCs (mdn 23 cells/ml, range 2 to 249), whereas with Veridex, 14 (67%) pts had > 5 CTC/7.5 ml (mdn 5 cells/7.5 ml, range 0 to >200). 0/7 (0%) with high AR responded to AA+P or E, 8/14 (53%) with low AR had a PSA decline and stable radiographic disease (median follow-up 12 wks). Variations in AR protein expression and localization heterogeneity was seen in all pts to varying degrees. 6/21 (29%) Pts demonstrated CK- CTC/CTC ratio >50% (mdn 9 cells/ml, range 5-38). ERG rearrangement and PTEN loss were correlated. Conclusions: Epic CTC analysis provides higher detection rates, while enabling individual cell analyses for predictive biomarkers of sensitivity to AR directed therapies. Notable was the marked heterogeneity of detection of AR, ERG, and PTEN of individual CTCs. Studies are ongoing to further explore associations with outcomes. [Table: see text]
A randomized phase I/II study to examine the contribution of carboplatin to cabazitaxel for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) with and without anaplastic features.
Authors: Corn Paul Gettys , Tu Shi-Ming , Zurita Amado J. , Araujo John C. , Pagliaro Lance C. , Logothetis Christopher , Aparicio Ana 
Published: February 2017

148 Background: We recently described “anaplastic” prostate carcinomas (PC), a clinically distinct variant of lethal castration-resistant prostate cancer (CRPC) that share clinical features with small cell carcinomas despite heterogeneous morphology. To test the hypothesis that anaplastic PC are uniquely sensitive to platinum-based chemotherapy, we designed a randomized study of cabazitaxel with or without carboplatin in men with metastatic CRPC (mCRPC) stratified for the presence of at least 1 of 7 previously published anaplastic criteria (Aparicio, Clin Cancer Res 2013;19). Here we report results of the phase I study. Methods: Patients (pts) received intravenous cabazitaxel with carboplatin every 21 days with growth factor support and were imaged every two cycles. A 3+3 sequential dose-escalation design was employed to assess the frequency of dose-limiting toxicity after cycle one and establish a maximal tolerated dose (MTD). Three cohorts were tested: (i) cabazitaxel 20mg/m2 – carboplatin AUC 3, (ii) cabazitaxel 25 mg/m2 – carboplatin AUC 3, and (iii) cabazitaxel 25 mg/m2 - carboplatin AUC 4. Up to 10 cycles were administered in the absence of progression or toxicity. Results: Nine men with mCRPC (five anaplastic) previously treated with docetaxel, received a median of six cycles (2 to 10). All had bone involvement and 6 of 9 had RECIST measurable disease. An MTD was not identified. All pts reported 1 or more adverse event (AE) possibly treatment related (120 Grade 1; 53 Grade 2; 13 Grade 3), most commonly fatigue, anemia, nausea, and diarrhea. Grade 3 AE included anemia (n=2), fatigue (n=1), thrombocytopenia (n=1), hypomagnesemia (n=1), diarrhea (n=1), hypokalemia (n=1), and anorexia (n=1). Prostate-specific antigen declines of more than 70% occurred in 6 of 9 (67%) pts. Two of 6 pts had a partial response, three had stable disease, and one progressed. For pts with elevated bone markers at baseline, 2 of 3 had more than 50% declines in BAP and 4 of 7 had more than 30% declines in urinary N-telopeptide levels. Conclusions: The combination of cabazitaxel and carboplatin is safe and has significant clinical activity. The randomized phase II portion combines cabazitaxel 25 mg/m2 and carboplatin AUC4. Results will be updated at the time of the meeting. Clinical trial information: NCT01505868.