bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of treatment outcomes in early stage hepatocellular carcinoma (HCC) detected in a surveillance program
Authors: Chan S. L. , Mo F. K. , Koh J. , Hui E. P. , Yu S. C. , Lai P. B. , Chan H. L. , Chan V. T. , Chan A. T. , Yeo W. , Mok T. 
Published: August 2020

4584 Background: Surveillance for HCC in hepatitis B virus (HBV) carriers aims to improve survival by detection of early resectable tumor. In 2005, our group reported low surgical resection rates despite detection of small sized tumors in a prospective surveillance cohort of 1018 HBV carriers (Mok TS et al. J Clin Oncol 05). In current study, we aim to identify predictive factors for treatment outcomes in HCC detected from our surveillance program. Methods: The prospective cohort was recruited at the Prince of Wales Hospital between Oct 1997 and Nov 2000. We updated the database in Dec 2008 and performed univariate and multivariate analysis on clinical (age, sex, cirrhosis, ascites, anti-viral therapy, bilirubin, ALT, albumin, INR), tumorous (size, number, resection) and virologic factors (HBV DNA, Genotype) for prediction of outcome in HCC patients (pts). Results: In the prospective cohort, total 923 HBV carriers were updated (95 lost to follow-up). After median follow-up of 9.95 years, we confirmed diagnosis of 105 HCC. Median age = 51 (range: 40–69); M:F = 82:23; Child's A and B cirrhosis = 38:67. Fifty seven pts (54.3%) had solitary tumor but only 34 (32.4%) are amenable to resection. Absence of cirrhosis (p=0.0072) and normal albumin level (p=0.0379) are predictors of surgical resection while tumor size and number are not. The median survival of all HCC pts was 2.26 years. Anti-viral therapy during the surveillance period is a strong predictor of survival (3.74 vs. 1.63 years; p=0.0115). In multivariate analysis, both anti- viral therapy (HR=0.35; 95%CI: 0.19–0.73; p=0.0041) and normal bilirubin level (HR=0.30; 95% CI: 0.25–0.80; p=0.0069) were predictive of improved survival in pts with HCC. The benefits of anti-viral therapy applied to both surgical and non-surgical candidates (p=0.17). Conclusions: Anti-viral therapy is a potent predictor of survival of HBV related HCC. Liver function is more important than tumor characteristics in determining the outcome of HCC detected in the surveillance program. No significant financial relationships to disclose.
A phase II study of bevacizumab (B) and erlotinib (E) in combination for Asian patients (pts) with advanced/metastatic hepatocellular carcinoma (HCC): An interim safety report
Authors: Hsu C. , Kang Y. , Yang T. , Su W. , Sandoval-Tan J. , Chiou T. , Jin K. , Button P. , Hsu C. , Cheng A. 
Published: August 2020

4585 Background: Asian pts with advanced HCC have a poor prognosis, and a median survival of 2–4 months with best supportive care (ph III). As HCCs are highly vascular tumors, dual inhibition of VEGF and EGFR with B plus E is an attractive combination strategy. B has demonstrated promising phase II results in 34 HCC patients, with 75% non-progression at 16 weeks (wks) (65% in Caucasians) (Thomas et al., 2007). However, 6–11% of pts had variceal bleeding, some cases of which were fatal. This study was initiated to investigate the safety and efficacy of B+E in Asian HCC pts. Methods: Screening esophagogastroduodenoscopy (EGD) was used to exclude pts with high risk of variceal bleeding. Asian pts with advanced/metastatic, measurable HCC who were unsuitable for surgery or other loco-regional therapies received B 5mg/kg q2w i.v. and E 150mg/day orally. The primary endpoint was PFS at 16 wks. Responses were evaluated using RECIST. Tumor tissue samples were collected for biomarker analysis. Results: Baseline characteristics of the 51 pts enrolled between March and October 2008 were median age: 58 years (range 26–84); male/female: 44/7; ECOG PS 0/1/2: 30/20/1; Child-Pugh A/B: 50/1; BCLC stage C n=44 (88%); hepatitis B/C/B+C/nonB+nonC: 42/4/3/2; grade I/II varices n=16 (none with red sign). Pts received a median 8 wks of study treatment. No variceal bleeding was observed; 3 pts had upper GI bleeding (grade 1/2; 2 peptic ulcer, 1 gastritis). See table for most common toxicities. 7/10 deaths were due to disease progression, none were due to study treatment. At the time of analysis, 2 pts had a confirmed partial response (PR; duration 24+ and 8+ wks). 1 pt with an unconfirmed PR continued on treatment. Data for the primary analysis were immature. Conclusions: Bevacizumab plus erlotinib was well tolerated. Screening EGD was feasible and reduced the risk of variceal bleeding. Follow-up is ongoing. [Table: see text] [Table: see text]
Circulating tumor cells (CTCs) as a surrogate marker for determining response to chemotherapy in advanced gastric cancer (AGC)
Authors: Matsusaka S. , Chin K. , Mizunuma N. , Ogura M. , Suenaga M. , Shinozaki E. , Terui Y. , Hatake K. 
Published: August 2020

4600 Background: The purpose of this study was to quantitate circulating tumor cells (CTCs) in advanced gastric cancer (AGC) patients and to demonstrate the role of CTCs in cancer therapy. This study investigates the hypothesis that CTC levels can predict clinical outcomes in patients with AGC. Methods: Eligibility criteria: PS (ECOG) of 0 to 2; histopathology of adenocarcinoma; adequate major organ functions. Chemotherapy regimen was S-1 based regimen (S-1 with or without cisplatin) or paclitaxel. Treatment was continued unless disease progression was observed. CTCs of whole blood in baseline, 2 week and 4 week after initiation of chemotherapy were isolated and enumerated using immunomagnetics. Results: From November 2007 to September 2008, thirty patients with unresectable or recurrent gastric cancer were enrolled onto a prospective study. Pts characteristics were as follows: median age: 60 years (range 24–78), PS 0/1/2: 21/8/1, primary tumor ±: 21/9 and regimen S-1/S-1with cisplatin/paclitaxel: 3/15/12. Among 30 pts, best response rates were 36.7% (CR/PR/SD/PD: 0/11/8/11). Patients with ≥4 CTCs at 2 week points and 4 week points had the shorter median progression-free survival (PFS) (1.4, 1.4 months, respectively), than the median PFS of <4 CTCs (6.3, 6.3 months, respectively) (logrank test; p=0.0008, p=8.78E-07, respectively). A finding of <4, CTCs of 2 week and 4 week after initiation of chemotherapy was associated with significantly longer overall survival (OS) as compared with these patients with ≥4 CTCs (p=0.016702, p=0.027788 respectively). Conclusions: These data demonstrate that CTC measurement may be useful as a surrogate marker for determining response to S1 based regimen or paclitaxel regimen in AGC. No significant financial relationships to disclose.
A randomized phase II trial of adjuvant chemotherapy with cisplatin, epirubicin, 5-fluorouracil, gemcitabine (PEFG regimen) or gemcitabine alone after curative resection for pancreatic cancer
Authors: Reni M. , Cereda S. , Aprile G. , Tronconi M. C. , Milandri C. , Passoni P. , Rognone A. , Balzano G. , Di Carlo V. , Villa E. 
Published: August 2020

4608 Background: The PEFG regimen yielded a statistically relevant outcome advantage as compared with gemcitabine (G) in patients with advanced pancreatic adenocarcinoma (PA). The current trial assessed the impact upon disease control of PEFG regimen and single agent G after curative resection for PA. At time of trial design, both arms were experimental since the role of adjuvant therapy in PA was debated. Methods: After R0 or R1 resection for PA, patients with stage IB-III disease, aged 18–70 years, Karnofsky performance status (PS) >60 were randomized within 8 weeks from surgery to receive either G 1 g/m2/weekly Q3 every 4 weeks (Arm A), or PEFG (cisplatin and epirubicin at 40 mg/m2 each on day one, gemcitabine at 600 mg/m2 on days 1 and 8 and 5-FU at 200 mg/m2/day on days 1 to 28) every 4 weeks (Arm B). In both treatment arms chemotherapy was administered for 3 months and followed by radiotherapy (54–60 Gy in 27–30 fractions) with concurrent 5-FU 250 mg/m2/day. A CT scan was performed every three months. The primary endpoint was the probability of being disease-free at 1 year (DFS1y) from surgery. The Fleming design was used to calculate the sample size. Assuming P0=35% and P1=55%, α .05 and β.10, the study was to enroll 51 patients per arm. The treatment arm had to be considered of interest with > 23 patients being DFS1y. Results: Between August 2003 and August 2008, 102 patients were enrolled, stratified by center and resection margin and randomized (51 per arm). All patients were eligible. One patient in arm A and 2 in arm B refused the assigned treatment. An intent-to-treat analysis was performed. Patients’ characteristics were (A/B): median age 61/60, median PS 90/90, stage IIA 19/12%; stage IIB 73/81%; stage III 8/7%; grade 3 30/46; R1 36/30; pre- and post-surgery surgery CA19.9 > upper limit of laboratory normal 68/80% and 29/33%, tumor size > 2.9 cm 41/43%. To date, 41 patients per arm are assessable for the primary endpoint: 19 (46%) and 28 (68%) patients were DFS1. Main G3–4 toxicity was: neutropenia in 21/85% and thrombocytopenia in 0/23% of patients. Conclusions: With a mature follow-up for 80% of patients, PEFG reached the primary endpoint of the trial and warrants further study while G not yet. No significant financial relationships to disclose.
Detection of early-stage pancreatic carcinoma
Authors: Gold D. , Modrak D. E. , Newsome G. , Karanjawala Z. , Hruban R. , Goggins M. , Goldenberg D. M. 
Published: August 2020

4613 Background: Invasive pancreatic carcinoma is a virtually lethal disease, mostly because of the failure to detect it at a sufficiently early timepoint for successful treatment. Our laboratory has identified a unique biomarker detected by MAb PAM4 that shows high specificity for a mucin glycoprotein expressed by pancreatic carcinoma (PC). While identified in almost 90% of PC and its precursor lesions, the antigen is not detectable in normal pancreas. We are investigating this biomarker for the early detection of PC. Methods: Both immunohistochemical (IHC) and enzyme immunoassay (EIA) were employed for detection and/or quantitation of PAM4-mucin in tissue and sera, respectively. Results: We have extended our prior IHC results with precursor lesions (Clin Cancer Res 2007;13:7380–7); PAM4 gave an intense, diffuse labeling pattern in 81% of mucinous cystic neoplasms (MCN), with an additional 11% showing a focal pattern (n=27). Thus, a total of 92% of MCN showed evidence of PAM4-antigen expression. Of interest, a difference in the labeling pattern was observed in association with the grade of dysplasia, providing easy identification of MCN with high- grade dysplasia. We previously reported use of an EIA for quantitation of PAM4-antigen in sera. The assay demonstrated a sensitivity and specificity of 77% and 95%, respectively, for identification of PC (J Clin Oncol, 2006;24:252–8). We have now confirmed these results in a set of serum specimens (n= 49 PC, 13 normal) for which staging information was available. Overall specificity and sensitivity were 82% and 85%, respectively, calculated by ROC curve analysis (AUC=0.878±0.045; 95% CI=0.769–0.947). Although only a small number of specimens were from patients with stage I disease (n=12), 92% of these were above the cutoff value for positive response. A correlation was observed for average concentration of antigen in the circulation with stage of disease (R2=0.988). Conclusions: IHC and EIA results indicate that PAM4 identifies a biomarker for PC that is present at the earliest stages of neoplastic transformation, thus warranting controlled analyses of larger specimen numbers. (Supported in part by USPHS grant CA096924 from the NIH.) [Table: see text]
Multicenter study of radiosensitizing gemcitabine combined with fractionated radioimmunotherapy for repeated treatment cycles in advanced pancreatic cancer
Authors: Pennington K. , Guarino M. J. , Serafini A. N. , Rocha-Lima C. , Suppiah K. , Schneider C. J. , Gold D. V. , Sharkey R. M. , Wegener W. A. , Goldenberg D. M. 
Published: August 2020

4620 Background: In a phase I study, a single dose of 90Y-labeled anti-mucin humanized antibody, hPAM4 (90Y-hPAM4), led to several transient reductions or stabilization of lesions in advanced pancreatic cancer, with bone marrow toxicity limiting the maximum tolerated dose to 20 mCi/m2. Preclinical studies showed gemcitabine enhanced radioimmunotherapy, so a phase Ib study was undertaken to evaluate repeated treatment cycles of 90Y-hPAM4 plus gemcitabine. Methods: Patients (pts) with previously untreated, locally advanced or metastatic, pancreatic cancer were treated in 4-week cycles (200 mg/m2 gemcitabine once-weekly; 111In-hPAM4 the 1st wk for imaging, biodistribution, and dosimetry; 90Y-hPAM4 once-weekly the last 3 wks), which could be repeated in the absence of progression or unacceptable toxicity. The 90Y-dose was escalated by patient cohort following a 3+3 design, with tumor responses assessed by CT and FDG/PET imaging, and by CA19.9 serum levels. Results: Eight pts (3F/5M, 56–72 years old, 7 with metastatic disease) have now been treated at the first 2 dose levels (6.5 and 9.0 mCi/m2 90Y-hPAM4 x 3) with hematologic toxicity all transient Grade 1–2 (NCI CTC v3). 111In-hPAM4 imaging showed normal biodistribution, evidence of tumor targeting and acceptable dosimetry estimates to normal organs per treatment cycle. Two pts had tumor responses to initial treatment with significant decreases in FDG metabolic activity on PET imaging, regression of lesion sizes on CT, and CA19.9 decreases. Both pts continue in excellent performance status now at 9 and 11 months after study entry, after receiving a total of 3 and 4 treatment cycles, respectively, without additional toxicity. A 3rd pt with a stable response by PET and CT 4 weeks after initial treatment and decreases in CA19.9 levels is now undergoing a 2nd treatment cycle. Four other pts had early progression of disease by or before post-treatment week-4 evaluation, and the remaining pt is still being evaluated. Conclusions: Dose escalation is continuing after fractionated radioimmunotherapy with 90Y-hPAM4 plus low-dose gemcitabine demonstrated therapeutic activity at the first two 90Y dose levels, with minimal hematologic toxicity, even after 4 treatment cycles. [Table: see text]
E4201: Randomized phase II study of gemcitabine in combination with radiation therapy versus gemcitabine alone in patients with locally advanced, unresectable, pancreatic cancer (LAPC): Quality-of-life (QOL) analysis
Authors: Cardenes H. R. , Powell M. , Loehrer P. J. , Wagner L. I. , Cella D. F. , Brell J. , Ramanathan R. K. , Crane C. H. , Alberts S. R. , Benson A. B. 
Published: August 2020

4627 Background: E4201 compared radiation and gemcitabine (RT+Gem) versus Gem alone in LAPC. The primary endpoint was overall survival; secondary objectives included: objective response rate (RR), progression-free survival (PFS), toxicity and QOL. We previously reported that RT+Gem was associated with improved overall survival compared with Gem alone [median survival time, 11 months and 9.2 months, respectively; p=0.034], without impact in RR or PFS. (ASCO 2008, abstract # 4506). We now report on QOL as measured by the Hep subscale from the FACT-Hepatobiliary [FACT-Hep] between both arms. Methods: Eligible patients had LAPC adenocarcinoma, PS <2, without prior therapy. They were randomized to Arm A: Gem alone (1,000 mg/m2/week x 3, every 4 weeks, 7 cycles), or Arm B: RT (50.4Gy/28 fractions) plus Gem (600 mg/m2/weekly x 6) followed by 5 cycles of Gem alone (1,000 mg/m2/weekly x 3 every 4 wks). The FACT-Hep was administered at baseline (before starting induction), 6 weeks (immediately after completing induction), week 16 (Arm A) or week 15 (Arm B) mid-consolidation, and at 9 months. Results: From April, 2003 to December, 2005, 74 patients were enrolled, 71 were eligible [37 Arm A; 34 Arm B]. Grade ≥3 was reported in 80% and 82.4% in ARM A and B, respectively (p=1.00). Grade IV toxicities, mainly gastrointestinal and hematologic, were more common in ARM B (41.2% vs 5.7%, p=<0.0001). QOL compliance declined over time, most commonly attributable to either patients or staff choosing not to complete or administer the instrument due to declining health (96%, 69%, 60%, and 40% at baseline, week 6, 15/16 weeks and 9 months, respectively). Within Arm B, QoL scores dropped significantly from baseline to 6 weeks. By week 15, QoL scores for patients on Arm B rebounded to levels similar to baseline. Two-sided Wilcoxon rank sum tests failed to suggest differences in median FACT-Hep subscale score between treatment arms at any of the four time-points (alpha = 0.10). Conclusions: RT+Gem is associated with an overall survival benefit without apparent long term adverse impact on QOL when compared with Gem alone. No significant financial relationships to disclose.
Phase I study of intravenous Seneca Valley virus (NTX-010), a replication competent oncolytic virus, in patients with neuroendocrine (NE) cancers
Authors: Rudin C. M. , Senzer N. , Stephenson J. , Loesch D. , Burroughs K. , Police S. R. , Hallenbeck P. 
Published: August 2020

4629 Background: NTX-010 is a naturally occurring replication competent picornavirus with potent and selective tropism for human NE tumors, including small cell cancers and carcinoid. NTX-010 elicts rapid cytolysis in vitro and durable responses following IV dosing in multiple xenograft models. Methods: A first-in-human phase I study of IV NTX-010 was conducted across 5 log-increment dose cohorts from 107 vp/kg to 1011 vp/kg, in patients with NE cancers. Study endpoints included toxicity assessment, response assessment, evaluation of viral titers and clearance in blood, sputum, nasal swabs, urine, and stool, and assessment of neutralizing antibody (Ab) development. Results: 30 patients were treated (6 small cell, 24 carcinoid-type). All small cell patients were heavily pretreated (> third line) and received 107 vp/kg. In these patients, median PFS was 1.2 months and median OS was 4.1 months, including 1 long term (16 month +) survivor with prolonged SD after progressing through prior therapies. Carcinoid patients in cohorts 1–4 have 70% SD rate and median PFS of 5.4 months (95% CI 3.6 to NE); median OS has not been reached. Cohort 5, a 12 patient expansion cohort at 1011 vp/kg restricted to carcinoid, is still being monitored and shows promising antitumor activity including improvement in carcinoid syndrome symptoms, decline in 5HIAA and other serum markers, minor responses by CT scan, and an objective PET response (>50% decrease in SUV). There were no DLTs in any cohort. Evidence of intratumoral viral replication includes delayed kinetics in serum viral titer, post-infusion serum titers greater then the dose administered and positive immunohistochemistry and/or RT-PCR signal for viral antigens in tumor mass despite Ab production. Viral clearance was documented in all subjects and correlated temporally with development of antiviral Ab. Conclusions: NTX-010 is the first picornavirus to be evaluated as an anticancer therapeutic. A single IV dose of 1011 vp/kg of NTX-010 is safe, has predictable viral kinetics, and shows promising activity against NE tumors. Phase II testing of this novel agent either as a single agent or in combination with standard cytotoxic therapies is warranted. [Table: see text]
Phase II presurgical study of bevacizumab plus erlotinib in untreated patients with metastatic renal cell carcinoma
Authors: Jonasch E. , Tsavachdidou D. , Wood C. G. , Matin S. F. , Corn P. G. , Tamboli P. , Wang X. , Tannir N. 
Published: August 2020

5004 Background: The safety and efficacy of presurgical bevacizumab in patients with metastatic renal cell carcinoma (mRCC) is not known. The current study was designed to answer these clinical questions, and to define predictive tissue biomarkers using nephrectomy specimens from patients on trial. Methods: Patients with newly diagnosed clear cell mRCC whose primary tumor was considered resectable were enrolled. In this single arm phase II trial, patients received bevacizumab plus erlotinib or bevacizumab alone for 8 weeks, followed by restaging. Primary endpoint was progression free survival (PFS). If patients demonstrated progressive disease and had a declining performance status after eight weeks, nephrectomy was deferred. Postoperatively, patients continued on study drug(s) if disease stabilization or regression had occurred. Reverse phase protein arrays (RPPAs) were generated from nephrectomy specimens. Results: Between March 2005 and March 2008, 52 patients were enrolled on the study, and 50 were included in the analysis. By the Memorial Sloan-Kettering Cancer Center criteria, 82% of patients had intermediate-risk, and 18% had poor-risk features. Twenty-three patients received bevacizumab plus erlotinib, and 27 received bevacizumab alone. Forty-two patients underwent nephrectomy. Median progression-free survival was 11.0 months (95% CI: 5.5, 15.6 months). Median overall survival was 25.4 months (95% CI 11.4, not estimable). Two perioperative deaths occurred, and neither was attributable to study drug. Wound dehiscence resulted in treatment discontinuation for three patients. RPPA analysis demonstrated a clear separation of better versus worse responding patients. Conclusions: Presurgical treatment with bevacizumab therapy is relatively safe and yields clinical outcomes comparable to post surgical treatment with antivascular therapy in patients with mRCC. Prospective randomized trials testing the use of presurgical therapy to select appropriate patients for cytoreductive nephrectomy are warranted. [Table: see text]
Southwest Oncology Group S9921: Prolonged event-free survival in high-risk prostate cancer (PC) patients receiving adjuvant androgen deprivation
Authors: Glode L. M. , Tangen C. M. , Hussain M. H. , Wood D. P. , Swanson G. P. , Quinn D. I. , Dawson N. , Balzer-Haas N. , Crawford E. D. , Thompson I. M. 
Published: August 2020

5009 Background: Patients with adverse pathologic risk factors after radical prostatectomy are at high risk for biochemical relapse and eventual death from disease. Adjuvant hormonal therapy with or without chemotherapy may prolong event free survival. Methods: SWOG 9921 randomized 859 eligible high risk PC patients to receive 2 years of adjuvant combined androgen blockade (CAB) (goserelin + bicalutamide) with (433) or without (426) chemotherapy (mitoxantrone + prednisone). The primary endpoint is survival. The DSMC has approved this analysis. PSA was to be assessed every 3 mo for 5 yrs and then every 6 mo for 10 more yrs. PSA relapse was defined as 3 consecutive measurements > 0.2 ng/ml. Death w/o relapse is censored. The CAB only eligible group is being reported (n=426). Risk groups based on eligibility criteria are as follows: Risk Group 1= positive margins or extraprostatic extension only with Gleason 7; elevated PSA (pre-op > 15 ng/ml), or had a pre-op PSA > 10 ng/ml and a biopsy Gleason 7(N=113); Risk Group 2 = seminal vesicle invasion or Gleason >/= 8, but no positive nodes (N=240), Risk Group 3 =positive nodes (N=69), 397 patients from both arms who completed 2 years of CAB were assessed for time to testosterone (T) recovery. T was assessed every 6 mo until it reached the institutional lower limit of normal. The median follow-up time from randomization is 3.8 years. Results: See Table . The estimated median time to T recovery (> 50ng/ml) is 11.7 mo from the end of CAB (95% CI 11.3, 11.9 months). The 6 and 18 mo recovery rates were 16% and 89%. Of 17 deaths (including ineligibles), 7 were from prostate cancer; 4 from other cancers, one cardiovascular disease, and 5 from miscellaneous causes. Conclusions: These data indicate a markedly low PSA relapse and death rates in high risk PC patients who received CAB. This likely is the result of stage migration, patient selection and/or the effects of CAB itself. [Table: see text] [Table: see text]