bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends of clinical staging for cancer patients at primary presentation: Have we improved over time?
Authors: Reddy Sanjay S. , Handorf Elizabeth , Smaldone Marc C. , Ridge John A. , Farma Jeffrey M. , Sigurdson Elin R. 
Published: February 2017

737 Background: The efficacy of non-surgical and of neoadjuvant therapy for cancer cannot be determined without appropriate clinical staging. The absence of staging data has been a persistent problem. Methods: Using the National Cancer Database from 1998-2011 we reviewed patients diagnosed with cancers of three disease sites, head and neck (HNC), rectal (RC), and bladder (BC). Rates of clinical staging were assessed by institution type, either community (COM) or academic (ACA). Patients treated with surgery alone were excluded from analysis. Results: 166,670 patients with HNC, 125,699 patients with RC, and 15,433 patients with BC were identified. Prior to induction therapy, 91% and 92% of HNC patients were clinically staged in COM versus ACA, and 73% and 78% of RC patients, respectively (p<0.0001). BC patients were clinically staged 79% of the time in both institutions (p=0.43). Among HNC patients, clinical staging was assigned to 90% in 1998, which increased to 94% in 2011 (p<0.0001). For RC, clinical staging rates increased from 62% in 1998 to 89% in 2011 (p<0.0001). In BC, 74% were staged in 1998, which declined to 66% in 2007. However, the trend reversed, and 92% received a clinical stage by 2011 (p<0.0001). When comparing trends between COM and ACA, in 1998 stage was reported in 90% and 91% for HNC, respectively. By 2011, the proportions rose to 93% and 94%(p<0.0001). In 1998, 60% of RC patients were staged in the COM versus 66% in ACA. By 2011, 88% and 91% had staging reported (p<0.0001). For BC in 1998, 75% of patients were assigned a stage in both center types, which fell until 2007, when a steady increase was observed. By 2011, 92% of patients were staged in both center types (p<0.0001). Conclusions: Clinical staging improved in all classes of patients with time, although a substantial number still lack staging information. Clinical stage reporting varied by type of institution as well as disease sites. Patients with HNC had the highest rate of clinical staging prior to treatment and RC had the lowest. Between 1998 and 2011, RC has seen the most significant upward trend in recording clinical stage. Despite this, thousands of patients have received treatment without documentation of their clinical stage.
Liver resectability following S-1+L-OHP with cetuximab as the first-line treatment of unresectable liver limited metastases from KRAS exon 2 wild-colorectal cancer in Japanese patients (KSCC 1002).
Authors: Miyamoto Yuji , Emi Yasunori , Tokunaga Shoji , Beppu Toru , Kakeji Yoshihiro , Oki Eiji , Saeki Hiroshi , Mori Shinichiro , Inomata Masafumi , Akagi Yoshito , Baba Hideo , Natsugoe Shoji , Ogata Yutaka , Maehara Yoshihiko ,   Kyushu Study Group of Clinical Cancer (KSCC)
Published: February 2017

755 Background: There is no data concerning liver resectability following S-1+L-OHP (C-SOX) with cetuximab (Cmab) as the first-line treatment of unresectable liver limited metastases from KRAS exon 2 wild-colorectal cancer by prospective, multi-center study in Japan. The Kyushu Study group of Clinical Cancer (KSCC) conducted phase II trials in this setting. Methods: Eligibility criteria included unresectable liver limited metastases from histologically confirmed advanced colorectal cancer, ECOG PS 0-1 and adequate general condition. Patients (pts) received 4-6 cycles of C-SOX (oxaliplatin 130 mg/m2, day 1 followed by S-1 80 mg/m2 po [days 1-14] every 3 weeks) with weekly durable intravenous (DIV) Cmab administration at 400 mg/m2 (day 1) and 250 mg/m2/week (except day 1), followed by evaluating the liver resectability. Results: Of the 33 pts enrolled from March 2010 to July 2013; M/F, 20/13; median age, 64 years (range 48-83); ECOG PS 0/1, 27/6; primary lesion -/+, 18/15; number of liver metastasis 1-4/5 or more, 10/23; uni-/bi-lobular liver meta. 5/28; synchronous/metachronous 30/3. The number of FAS and SAS cases was 33. Response without confirmation for CR, PR, SD, PD and NE were 1 (3.0%), 20 (60.6%), 6 (18.2%), 3 (9.1%) and 3 (9.1%), respectively. An overall response rate was 63.6% (95% CI: 46.3–81.0%). The liver resectability for all time treatment was 16/33 (48.5%). The number of R0 cases was 13 pts (39.4%). Median progression free survival (liver resection was not censored and not event, events = relapse, progression, secondary cancer, and death) for 16 liver resection cases and 17 not-resection cases were 25.0 months (8.1-not reached), 4.5 months (3.0-10.8), respectively. Median overall survival (mOS) for all 33cases was 31.6 months (14.8, not reached). Median OS for 17 not-resection cases was 14.0 (6.4-not reached), and mOS for 16 liver resection cases was not reached and 3-year survival rate was 51.4%. Conclusions: C-SOX + Cmab regimen is safe and effective for unresectable liver limited metastases from KRAS exon 2 wild-colorectal cancer, and might be to lead the high liver resectability. Clinical trial information: UMIN000004331.
A phase I, dose-escalation, multicenter study of ACT-PFK-158, 2HCl in patients with advanced solid malignancies explores a first-in-human inhibitor of glycolysis.
Authors: Redman Rebecca Ann , Pohlmann Paula Raffin , Kurman Michael R. , Tapolsky Gilles , Chesney Jason 
Published: February 2017

TPS494 Background: In human cancers, loss of PTEN, stabilization of hypoxia inducible factor-1α, and activation of Ras and AKT converge to increase the activity of a regulator of glycolysis, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3). This enzyme synthesizes fructose-2,6-bisphosphate (F2,6BP), which is an activator of 6-phosphofructo-1-kinase, a crucial step of glycolysis that is tightly controlled by multiple metabolic feedback mechanisms and dictates the rate of glycolytic flow. The vast majority of pancreatic ductal adenocarcinomas and approximately 50% of colon adenocarcinomas harbor activating mutations in Ras and these tumors have been reported to be highly glycolytic. PFK158 is a potent small molecule inhibitor of PFKFB3 that is selectively cytotoxic to Ras-transformed epithelial cells and displays broad anti-tumor activity causing ~80% growth inhibition in several mouse models of human-derived tumors and syngeneic murine models of colon cancer. Importantly, IND-enabling safety and toxicity studies have demonstrated that PFK158 is well tolerated in rats and dogs with an expected good therapeutic index, lending support for a phase 1 trial that is now underway. Methods: The primary objective of the study is to describe the dose limiting toxicity and to determine either the maximum tolerated dose or biological effective dose of PFK-158 in a “3+3” cohort-based dose escalation design that follows a modified Fibonacci scheme. Multiple secondary endpoints have been incorporated to assess the effects of PFK-158 on peripheral blood mononuclear cell F2,6BP activity and on glucose uptake using FDG-PET imaging. This trial is currently enrolling at two US sites; Cohort 1 has been completed without dose-limiting toxicity and Cohort 2 is enrolling with two subjects under treatment as of September 2014. In conclusion, PFK158 is the first-in-man and first-in-class PFKFB3 inhibitor to be examined in a phase I trial and may have significant clinical utility either as a monotherapy or when combined with other targeted agents. Clinical trial information: NCT02044861.
A phase II clinical trial of carbon-ion radiotherapy and concurrent S-1 chemotherapy for locally advanced pancreatic cancer.
Authors: Shinoto Makoto , Shioyama Yoshiyuki , Suefuji Hiroaki , Matsunobu Akira , Toyama Shingo , Kudo Sho 
Published: February 2017

TPS504 Background: Despite recent advances in chemotherapy and radiotherapy, prognosis of unresectable locally advanced pancreatic cancer (LAPC) patients remains poor. To improve the outcome, a phase I/II clinical trial of carbon-ion radiotherapy (CIRT) with concurrent gemcitabine for LAPC was started in National Institute of Radiological Sciences in Japan.When compared to photon beams, carbon ion beams offer improved dose distribution, enabling us to concentrate a sufficient dose within a target volume while minimizing the dose in the surrounding radiosensitive normal tissue. In addition, carbon ions being heavier than protons provide a higher biological effectiveness, which increases with depth reaching the maximum at the end of the beam’s range. Although CIRT is expected to offer powerful local effect, whereas the potential risk of distant metastasis represent a critical problem for LAPC. To control distant metastases and subsequently prolong patient survival, a more effective systemic treatment might be essential. Recently, S-1 has shown favorable antitumor activity in several clinical trials for pancreatic cancer. Oral S-1 also has a great clinical advantage because the risks of complications associated with intravenous administration are avoided.We considered oral S-1 to be an attractive alternative to gemcitabine in the CIRT for LAPC. Thus, we planned a phase II clinical trial to evaluate the efficacy and safety of CIRT with concurrent S-1, which is the first trial in the world. Methods: Eligibility included pathological confirmation of pancreatic invasive ductal carcinomas and radiographically unresectable disease without metastasis. Concurrent S-1 is administered orally twice a day at a dose of 80mg/m2/day for 28 days every 6 weeks. Carbon-ion radiotherapy is prescribed with 55.2GyE at 12 fractions in 3 weeks. The primary endpoint is two year overall survival. Clinical trial information: UMIN000013803.
Physical activity in patients with unresectable pancreatic adenocarcinoma: A multicentric randomized controlled study (APACaP study).
Authors: Neuzillet Cindy , Vergnault Mathieu , Foucaut Aude-Marie , Touillaud Marina , Bonnetain Franck , Hammel Pascal ,   GERCOR
Published: February 2017

TPS506 Background: Exercise during chemotherapy (CT) is a promising strategy to reduce fatigue and improve health-related quality of life (QoL). It has been shown feasible and efficient in various cancers, including at advanced stage. Effects of physical activity in advanced pancreatic ductal adenocarcinoma (PDAC) have never been explored to date. We aim to evaluate the effects of a physical activity intervention in this setting. Methods: Randomized national multicentric interventional study to test the efficacy of an unsupervised home-based 16-week physical exercise program. Specificities of PDAC for physical activity program implementation will be taken into account (physical activity partner instead of patients groups, nutritional management). Main inclusion criteria: histologically confirmed, unresectable PDAC; scheduled for CT; WHO PS 0-2; age ≥ 18; physical activity partner. Two study arms: intervention group invited for the exercise program (aerobic and resistance exercises) in addition to usual care; control group receiving usual care alone. Primary objective: effects on fatigue (MFI-20) and health-related QoL (EORTC-QLQ-C30) at week 16, unified as co-primary endpoint. Secondary objectives: effects on pain, anxiety and depression, nutritional status, insulin resistance, CT tolerance, survival; adherence to the program. Number of patients: 200. PDAC patients are strongly affected by fatigue, thus they are expected to benefit from a physical activity intervention. Moreover, exercise may have a beneficial effect on tumor outcomes, by reducing insulin resistance and insulin/IGF-1 secretions. Such intervention may appear challenging because of multiple cancer-related symptoms (fatigue, depression, pain, denutrition) that can appear as barriers to physical activity. Conversely, we hypothesize that a physical exercise program, by taking into account PDAC specificities, may improve symptoms and health-related QoL. If this intervention is proven to be feasible and effective, such standardized physical exercise programs might be proposed in complement to CT in patients with advanced PDAC as a logical next step. Clinical trial information: NCT02184663.
A pilot study of AMP-224—a PD-1 inhibitor—in combination with stereotactic body radiation therapy (SBRT) in patients with metastatic colorectal cancer.
Authors: Duffy Austin G. , Makarova-Rusher Oxana V. , Fioravanti Suzanne , Walker Melissa , Venkatesan Aradhana , Abi-Jaoudeh Nadine , Wood Bradford J. , Citrin Deborah E. , Greten Tim F. 
Published: February 2017

TPS788 Background: AMP-224, a B7-DC Fc fusion protein, binds to PD-1, an inhibitory receptor that is present on the cell surface of exhausted, activated, effector, and memory T cells. AMP-224 has a unique mechanism of action in that it binds specifically to PD-1HI T cells (chronically stimulated / exhausted T cells) but not to PD-1LOcells which represent the normal activated T cell population. Several preclinical studies have documented an increase in peripheral antitumor immunity following radiation, a phenomenon known as the “abscopal effect”. Tumor PD-L1 expression has also been shown to be induced by radiation, which can suppress the anti-tumor immune response. Inhibition of PD-1/PDL-1 axis has been shown to improve anti-tumor immunity by blocking the tumor-mediated suppression of cytotoxic T cells. The aim of the study is to evaluate whether the anti-tumor immunity of anti-PD1 therapy (with AMP-224) can be enhanced by radiation therapy. Methods: Patients with histologically confirmed metastatic colorectal cancer to liver are being enrolled to this pilot study. The objectives are to determine the safety, tolerability and feasibility of AMP-224 in combination with stereotactic body radiation therapy (SBRT) to metastatic hepatic metastasis in patients with advanced colorectal cancer. Select eligibility are as follows: at least 1 measurable metastatic hepatic lesion by RECIST 1.1 criteria and amenable to SBRT. Patient must have progressed on or been intolerant of at least one prior oxaliplatin- and/or irinotecan-containing regimen and have metastatic lesions that are not amenable to curative resection; ECOG ≤ 1; Life expectancy of greater than 3 months. Acceptable organ and bone marrow function. No active or prior documented autoimmune or inflammatory disorders. Clinical trial information: awaited.
Disparities in baseline magnetic resonance imaging (MRI) utilization and imaging characteristics for prostate cancer (PCa) patients.
Authors: Ajayi Ayobami , Rosen Mark Alan , Vapiwala Neha , Both Stefan , Agawu Atu , Christodouleas John Paul , Bekelman Justin E. , Tochner Zelig , Deville Curtiland 
Published: February 2017

119 Background: Blacks with low risk PCa more likely to have adverse pathologic features at prostatectomy and larger dominant intraprostatic lesions (DIPL) with high anterior foci prevalence. Whether pretreatment MRI identifies these differences is unknown. The aim of this study was to determine whether disparities exist in MRI utilization and imaging characteristics for PCa patients. Methods: An institutional database of 617 PCa patients treated with proton and/or intensity modulated radiotherapy from 2005-2013 identified patients with pelvic MRI (T2 weighted, diffusion weighted, and/or dynamic contrast-enhanced sequences, 91% with endorectal coil). DIPL presence, size, extracapsular extension (ECE) and seminal vesicle invasion (SVI) were reviewed. Whites vs. Blacks overall and stratified by risk group were compared using Fishers exact test for categorical and student’s t-test for continuous variables (P<0.05 significant). Results: Race was 367 White (59%), 208 Black (34%), and 42 Asian/Other (7%). Age (mean 67±8), Gleason score, and risk group did not differ significantly for Whites vs Blacks; clinical stage and mean PSA (ng/mL) did (White 8±11 vs Black 14±22, P<0.001). Overall, 472 (77%) patients underwent baseline MRI, with Blacks (67%) less likely than Whites (81%), P<0.001. The disparity was greatest for low-risk Blacks (47% vs 90%, P<0.001), not significant in the intermediate-risk group (70% vs 78%, P=0.205), and reversed in high-risk (94% vs 75%, P=0.007). There were no significant differences in DIPL presence, diameter, area, ECE, or SVI overall or within low- and intermediate-risk groups. For high-risk, Blacks demonstrated smaller DIPL in maximum diameter 17 ± 8 mm (vs 21 ± 10; P=0.042) and area 185 ± 156 mm2(vs 295 ± 285; P=0.042), with no differences in DIPL presence, additional IPLs, ECE, or SVI. Conclusions: In this urban, academic center cohort, Black PCa patients were significantly less likely to undergo staging MRI. No differences were found in DIPL presence, area, ECE, or SVI, except in the high-risk group. Further investigation is required to better understand how pretreatment MRI utilization and imaging characteristics differ by race.
Radiogenomics of prostate cancer: Association between qunatitative multiparametric MRI features and PTEN.
Authors: VanderWeele David James , McCann Stephanie , Fan Xiaobing , Antic Tatjana , Jiang Yulei , Oto Aytekin 
Published: February 2017

126 Background: Better methods are needed to assess prior to prostatectomy the risk of aggressive prostate cancer. Radiogenomics is a promising new paradigm that aims to gain molecular and genomic insights from clinical images. Loss of PTEN expression correlates with clinically aggressive disease and is associated with a 7-fold increase in the risk of prostate cancer death. Methods: From 38 patients who had undergone multi-parametric prostate MRI prior to prostatectomy, a pathologist and a radiologist simultaneously identified 45 peripheral-zone cancer regions of interest (ROIs). Histologic sections of the cancer foci underwent immunohistochemical analysis and were scored according to percent of tumor cells expressing PTEN as: negative (0-20%), mixed (20-80%), or positive (80-100%). From the MRI ROIs, the average and 10th percentile ADC values, T2-weighted signal-intensity histogram skewness, and quantitative perfusion parameters were calculated. Both dynamic perfusion two-compartment model and an empirical mathematical model (EMM) were used to fit the average contrast concentration curves within the ROIs as a function of time. Associations between the quantitative image features and PTEN expression were analyzed with Pearson's correlation coefficient (r). Results: The PTEN scores were: positive (n = 21, 47%), mixed (n = 12, 27%), and negative (n = 12, 27%). Two perfusion imaging contrast uptake parameters obtained from EMM correlated with PTEN scores (r = 0.25, p < 0.1 and r = 0.43, p < 0.01), and T2-weighted signal-intensity skewness also showed some correlation tendency (r = −0.25, p < 0.1). No correlation was seen between mean ADC and 10th percentile ADC values and PTEN score. Conclusions: This preliminary study of radiogenomics of prostate cancer suggests that fast contrast uptake of cancer on DCE-MR imaging and a T2-weighted imaging feature are potentially associated with prostate cancer PTEN expression, which warrants further studies and validation.
Effect of radium-223 dichloride (Ra-223) on pain from US EAP.
Authors: Morris Michael J. , Sartor A. Oliver , Vogelzang Nicholas J. , Shore Neal D. , Cislo Paul , Bangerter Keith , Sweeney Christopher 
Published: February 2017

160 Background: Ra-223, a first-in-class alpha-emitting radiopharmaceutical, has shown pain palliation in phase 2 trials (Parker 2013; Nilsson 2012). Here we present the results of Ra-223 effect on pain from US EAP. Methods: Pain was assessed at baseline, during treatment (trt) , and follow up (up to 6 mos after last trt visit) using the Brief Pain Inventory (BPI-SF) Questionnaire. The pain severity assessment was based on the worst pain item from the BPI-SF. The analysis was restricted to those not on opioids at baseline due to missing data for those on opioids. Hypotheses tests were based on changes from baseline. A meaningful change in score was defined as >2 points from baseline (Atkinson 2010). Results: Of 177 treated patients (pts) with baseline pain scores, 109 were not on opioids at baseline (6% had a score of 0 [no pain], 46% had 1-4 [mild pain], 34% had 5-7 [moderate pain], 14% had 8-10 [severe pain]). A significant decrease in mean pain severity from baseline (P<0.05) was observed at all trt visits. Among 97 pts who could have pain improvement (baseline score ≥2), 57 (59%) experienced a reduction in pain during at least one on-trt visit. Among all pts not on opioids at baseline and had baseline pain assessment, 46/109 (42%) had improved pain without worsening (decrease of ≥2 points), 20/109 (18%) had stable pain (no change of ≥2 points), 30/109 (28%) had worsening of pain (increase of ≥2 points or initiation of opioids) at some point and never had improvement, 11/109 (10%) had improvement and worsening at different times during trt, and 2/109 (2%) had no post baseline data. (Table presents data at each trt visit). Conclusions: Radium-223 was associated with meaningful pain relief in 42% of pts, whereas 28% had worse pain and 18% no change. The confounding effect of change in opioids after initiation prevents adequate interpretation of this finding for pts on opioids at baseline. Clinical trial information: NCT01516762. [Table: see text]
Preliminary activity of veliparib (V) in BRCA2-mutated metastatic castration-resistant prostate cancer (mCRPC).
Authors: Pahuja Shalu , Appleman Leonard Joseph , Belani Chandra Prakash , Chen Alice , Chu Edward , Beumer Jan Hendrik , Puhalla Shannon 
Published: February 2017

170 Background: Male BRCA mutation carriers have a 2-8-fold increased risk of prostate cancer when compared to the general population, and up to 3% of patients (pts) with prostate cancer carry an inherited mutation in BRCA1 or 2. The therapeutic implications of germline BRCA mutations in prostate cancer are largely unknown. BRCA mutation enhances sensitivity to inhibition of the PARP1 and PARP2 enzymes, due to a synthetic lethal effect on DNA repair. We therefore conducted a phase 1 study of the PARP 1, 2 inhibitor, veliparib (V), in 2 cohorts of pts- BRCA germline mutated (BRCA+) and BRCA-wild type (BRCA-wt; consisting of serous ovarian cancer and triple-negative breast cancer). Methods: A 3+3 dose escalation phase I trial was performed to determine a maximum tolerated dose (MTD) and recommended phase II dose (RP2D). V was administered orally continuously on a 28-day cycle. Results: A total of98 (70 BRCA+ and 28 BRCA-wt) pts were enrolled. The maximum administered dose (MAD) was 500 mg BID and the MTD/RP2D was 400 mg BID. In BRCA+ cohort at doses ≥ 400 mg BID, overall response rate (ORR) defined as complete response (CR)+ partial response (PR) was 37%, and clinical benefit rate (CBR) defined as CR+PR+stable disease (SD) > 6 cycles was 40%. Three pts with BRCA2+ metastatic castration-resistant prostate cancer (mCRPC) were enrolled on the RP2D and were evaluable for response. In these pts, the ORR was 2/3 (66%) and CBR 3/3 (100%) (summarized in table). One pt with rapidly progressive mCRPC involving liver and bone achieved PR and undetectable serum PSA, and remains on therapy at 19+ cycles. The most common adverse effects in these pts were grade 1/2 nausea/vomiting, fatigue, and leukopenia consistent with the overall study population. Conclusions: Single-agent V demonstrates evidence of activity in BRCA2+ mCRPC. These data support the role of genotype-directed therapy in prostate cancer. Clinical trial information: NCT00892736. [Table: see text]