bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ofatumumab in combination with high-dose methylprednisolone for the treatment of patients with relapsed or refractory chronic lymphocytic leukemia.
Authors: Castro Januario E. , Choi Michael Y. , Carvajal Tomas , Li Hongying , James Danelle Frances , Messer Karen , Kipps Thomas J. ,   CLL Research Consortium
Published: March 2020

7124 Background: We performed a phase II, single-arm, clinical trial evaluating ofatumumab in combination with HDMP for the treatment of patients with relapsed or refractory CLL. Methods: Patients received ofatumumab at the dose of 1,000 mg weekly (half the conventional dose) for 12 weeks, without monthly maintenance doses. The HDMP dose was 1,000 mg/m2for 3 days of each of 3 monthly cycles. Prophylactic medications included acyclovir, bactrim, fluconazole, and allopurinol. Results: 21 patients were enrolled at a single center. The median age was 63 years (range 46–76). The median number of prior therapies was 3. 24% had unfavorable cytogenetics (Del 17p or Del 11q) and 76% had CLL cells that expressed unmutated IgVH genes or high levels of ZAP-70. 24% were fludarabine-refractory. Treatment was well tolerated. The majority of adverse events were grade 1 or 2, including insomnia, anxiety, fatigue, and infusion reactions. There were no grade 4 toxicities.19% of patients had grade 3 neutropenia, and 5% had grade 3 thrombocytopenia. Other grade 3 toxicities were hyperglycemia (71%), non-melanoma skin cancer and other skin lesions (19%), as well as acute coronary syndrome, atrial fibrillation, renal calculi, pneumonia, and hypocalcemia (1 patient each). Responses were assessed two months after completion of therapy. The overall response rate was 81% (17/21) with 5% CR (1/21), 10% nodular PR (2/21), 67% PR (14/21), 14% SD (3/21), and 5% PD. The median follow-up time was 12 months (range 5-23). The median progression-free survival (PFS) time was 9.1 months (95%CI: 7.5-NA) and the median treatment-free survival (TFS) was 11.5 months (95%CI: 10.0-NA). Patients with Del 17p or Del 11q had a significantly lower overall response rate (p-value <0.001, fisher’s exact test). Conclusions: The combination of HDMP and ofatumumab is an effective, tolerable, non-myelosuppressive treatment regimen. We observed a higher ORR and longer PFS than those previously reported with single agent mAb. This regimen may be useful for patients who are unable to tolerate more aggressive, myelosuppressive therapies, or have not responded to other treatments.
Application of the French prognostic score (FPS) to assess overall survival (OS) in a U.S.-based cohort of patients (pts) treated with azacitidine (Aza).
Authors: Zeidan Amer , Sun Zhuoxin , Prebet Thomas , Greenberg Peter , Juckett Mark , Smith Mitchell Reed , Paietta Elisabeth , Gabrilove Janice Lynn , Erba Harry P. , Gore Steven , Tallman Martin S. ,   on behalf of the Eastern Cooperative Oncology Group
Published: March 2020

7126 Background: In pts with IPSS high-risk myelodysplastic syndrome (HR-MDS), Aza prolonged OS. The FPS was developed for Aza-treated HR-MDS pts based on 4 baseline clinical criteria: Performance status, karyotype, presence of circulating blasts, and RBC transfusion dependency (TD) (Itzykson et al, Blood 2011). The FPS discriminated 3 risk groups [low-risk [LR), intermediate-risk (IR), and high-risk (HR), with significantly different median OS at 32, 15, and 6 months (M), respectively. We sought to validate the FPS in a U.S.-based cohort. Methods: The North American Leukemia Intergroup Trial E1905 randomized 150 pts with MDS, CMML, and AML with dysplastic changes to Aza 50 mg/m2/day (d) for 10 d +/- entinostat (Ent) 4 mg/m2/d on d3 and d10. OS was defined as time from registration to death from any cause, with follow-up censored at last contact. Kaplan-Meier estimates were used for survival distribution. Results: The FPS could be determined for 115 pts. Median follow-up was 48.5 M. The median OS was significantly different between the HR, IR, and LR FPS groups in the 115 pts (9.7, 14.7, 25.3 M, respectively, log Rank test P=0.017), and for pts in Aza arm (n=55) (7.8, 19.3, 26.4 M, respectively, P=0.008), but not for patients in the Aza+Ent arm (n=60) (12.5, 12.4, 24.1 M, respectively, P=0.21). Using multivariate Cox model with WBC count, hemoglobin, disease type, and platelet TD, the prognostic effect of HR vs. LR FPS groups remained significant for the entire cohort (P=0.046) and for the Aza arm (P=0.037). No significant differences in response rates were observed. Conclusions: The FPS warrants further evaluation as a baseline prognostic tool that can define a subgroup of pts with lower probabilities of achieving survival benefit from Aza therapy. Such pts might be considered from alternative therapeutic interventions.
A randomized double-blind phase II study of the Seneca Valley virus (NTX-010) versus placebo for patients with extensive stage SCLC (ES-SCLC) who were stable or responding after at least four cycles of platinum-based chemotherapy: Alliance (NCCTG) N0923 study.
Authors: Molina Julian R. , Mandrekar Sumithra J. , Dy Grace K. , Aubry Marie-Christine , Allen Ziegler Katie L , Dakhil Shaker R. , Sachs Bradley A. , Nieva Jorge J. , Schild Steven E. , Burroughs Kevin , Williams Anthony , Rudin Charles M. , Adjei Alex A. 
Published: March 2020

7509 Background: NTX-010 is a naturally occurring replication-competent picornavirus with potent and selective tropism for SCLC tumor cells expressing neuroendocrine markers. A phase I study of NTX-010 showed evidence of antitumor activity in patients with SCLC. Methods: ES-SCLC patients (pts) with SD, PR or CR after at least 4 cycles of platinum-based chemotherapy were pre-registered to confirm diagnosis of SCLC with > 1 neuroendocrine marker by a central pathology review. Eligible pts were.randomized 1:1 to placebo (B) or NTX-010 (A). NTX-010 or placebo was administered intravenously as a 1-hour infusion in 100 mL normal saline as a single dose of 1 x1011vp/kg. Viral studies to determine distribution, clearance of the virus and the presence of neutralizing antibodies were done. The primary goal of this trial was to compare the progression-free survival (PFS) of arm A to B based on a sample size of 45 patients per arm to detect an improvement in median PFS from 3 to 5 months (m). A pre-planned interim futility analysis was done after 40 PFS events, and reported here. Results: The trial is permanently closed to accrual. One-hundred and twenty pts were pre-registered, of whom 58 were randomized. Baseline age, gender, ECOG performance status, and histology were balanced between arms. Median age was 63 (range: 44 - 82). 31% of pts had a PS of 0 and 69% of 1. Grade 4 adverse events were seen in 3 (12.5%) patients in arm A and none in arm B. Based on the interim futility analysis, PFS was 1.7 m (95% CI: 1.3-3.1) for arm A and 1.7 m (95% CI: 1.4-4.3) for arm B. Pts with viral RNA at 7 (7 pts) and 14 (6 pts) days had worse PFS compared to those with no detectable levels within arm A (1.0 vs 1.6 m, p=0.02; 0.9 vs. 1.2 m, p=0.06). Median follow-up in pts is 6.1 m. The 3-month OS estimates are 83% (95% CI: 69%-100%) and 85% (70%-100%) for arms A and B respectively. Conclusions: This phase II study showed no benefit in PFS for ES-SCLC patients receiving NTX-010. Pts with detectable virus at 7 and 14 days had worse PFS. Clinical trial information: NCT01017601.
The European Thoracic Oncology Platform Lungscape project: Clinical outcome data as a basis for molecular correlations in resected non-small cell lung cancer.
Authors: Peters Solange , Weder Walter , Meldgaard Peter , O'Byrne Kenneth John , Wrona Ania , Dooms Christophe , Hernandez-Losa Javier , Marchetti Antonio , Nicolson Marianne , Tan Qiang , Smit Egbert F. , Dingemans Anne-Marie C. , Savic Spasenija , Blackhall Fiona Helen , Baas Paul , Jantus-Lewintre Eloisa , Kerr Keith M , Dafni Urania , Rosell Rafael , Stahel Rolf A. ,   European Thoracic Oncology Platform (ETOP)
Published: March 2020

7514 Background: Lungscape allowed building the largest virtual biobank of radically resected NSCLC with comprehensive annotated clinical data, with the aims of expediting knowledge on biomarkers and facilitating translation of research to the clinic. Methods: 2,403 stage I-III radically resected NSCLC cases from 15 sites with mandatory comprehensive clinical annotations including at least 2 years of follow-up have been collected retrospectively. A systematic data review of every single case was performed. Relapse-free survival (RFS), time to relapse (TTR) and overall survival (OS) have been analyzed overall and by subgroups. Results: Median age of the cohort is 66 years, with 35% women, and respectively 14%, 32% and 49% never, current and former smokers. Histological types included 52% adenocarcinoma, 40% squamous cell carcinoma, and 4.5% large cell carcinoma and some rarer/mixed subtypes. As shown in the Table, median RFS, TTR and OS differ significantly by stage (p<0.001). Stage remained a significant predictor for outcome in the multivariate Cox models in the presence of other potential prognostic factors. Conclusions: This is the first report on the full Lungscape series based on 7th TNM classification on OS, RFS and TTR across clinical and pathological subgroups. This complete clinical dataset, in particular the information on TTR will be invaluable to investigate the impact of molecular characteristics on outcome, allowing refining TNM staging using biomarkers. Ultimately Lungscape will provide a platform for marker-driven trials of novel therapeutics. [Table: see text]
Pemetrexed-carboplatin adjuvant chemotherapy with or without gefitinib in resected stage IIIA-N2 non-small cell lung cancer harbouring EGFR mutations: A randomized phase II study.
Authors: Wang Si-Yu , Ou Wei , Li Ning , Sun Haibo , Zhang Liang , Fang Qin 
Published: March 2020

7519 Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) show great efficacy in patients with advanced non-small cell lung cancer (NSCLC) with EGFR mutations. The BR.19 trial exploring the role of adjuvant gefitinib in resected early stage NSCLC (stage IB 49%, II 38%, III 13%) did not show significant progression-free survival (PFS) or overall survival (OS) improvement in all patients. The efficacy of gefitinib following adjuvant chemotherapy in patients with EGFR mutation is unknown. Methods: In this open-label, phase II study, patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations (either the exon 19 deletion or L858R point mutation) were randomly assigned to receive pemetrexed (500mg/m2) and carboplatin (AUC=5), administered every 21 days for 4 cycles, followed with (n=30) or without (n=30) gefitinib (250mg per day) for 6 months. The primary end point was PFS. The second end point was OS. Results: From August 2008 toSeptember 2011, 60 patients (35 males and 25 females) were included in our center. Of the 60 patients (56 adenocarcinomas, 2 squamous cell carcinomas, 2 adenosquamous carcinomas), 20 patients (33.3%) had exon 19 deletion mutation, 40 (66.7%) patients had exon 21 L858R point mutation. The most common adverse event was rash (43.3%, 13 of 30) in the pemetrexed and carboplatin (PC)-gefitinib group and the addition of gefitinib to chemotherapy was well tolerated. The PFS was significantly longer among those who received PC-gefitinib than among those who received PC alone (median,39.8 months vs 27.0 months; hazard ratio [HR],0.369; 95% confidence interval [CI], 0.161-0.847; P=0.014). There was no significant difference in OS between the two group(median,41.6 months vs 32.6 months,P=0.066). The rates of 2-year PFS and OS were 78.9% and 92.4% in PC-gefitinib group, and 54.2% and 77.4% in PC alone group, respectively. Conclusions: The addition of gefitinib to pemetrexed and carboplatin adjuvant therapy showed significant improvement in PFS for patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations.
Examining the influence of incidentally using ACEI on survival outcomes in stage III non-small cell lung cancer patients treated with definitive radiotherapy.
Authors: Wang Hongmei , Liao Zhongxing X. , Zhuang Yan , Levy Lawrence B. , Xu Ting , Gomez Daniel Richard 
Published: March 2020

7521 Background: The influence of angiotensin-converting enzyme inhibitors (ACEIs) on tumor progression is controversial, with some reports showing an antitumor mechanism and others demonstrating an increased risk of progression while on these agents. Our aim was to better elucidate the effect of ACEIs on locally advanced non-small cell lung cancer (NSCLC) outcomes in the setting of conflicting prior results. Methods: We retrospectively reviewed 673 patients with stage III NSCLC who received definitive radiotherapy +/- chemotherapy. Cox proportional hazard models were utilized to determine the association between ACEI intake and locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). Results: Univariate analysis showed an increased hazard of LRP among patients who used ACEI. After adjusting for multiple variables, ACEI use remained significant. No association was found regarding DMFS, DFS, or OS (Table). Conclusions: The use of ACEI was associated with an increased risk of locoregional progression in this population of patients. These findings provide implications for continuing this treatment through radiation therapy, if further validated through prospective studies. [Table: see text]
Performance of a prognostic genomic signature for early-stage NSCLC in matched fresh frozen and RNA-stabilized tissue.
Authors: Huang Shuguang , Ewing Amy L , Reitze Nicholas J , Uihlein Arlette H , Wang Dakun , Gabrin Michael J , Keating Katherine E. , Mulligan Jude , Wilson Claire , Davison Timothy , McKenzie Stuart , Tsao Ming-Sound , Shepherd Frances A. , Brower Stacey L 
Published: March 2020

7532 Background: Recent clinical studies have demonstrated the benefit of adjuvant chemotherapy (ACT) in some early-stage non-small cell lung cancer (NSCLC) patients. A 15-gene signature, developed using fresh frozen (FF) tissue, has been shown to be an independent prognostic marker that identifies high risk patients who may benefit from ACT. Use of this signature in tissue preserved in an RNA stabilization reagent is desired for easier access to tumor tissue in the clinical setting. Methods: Matched FF and RNAlater-preserved (RNAL) tissues were obtained from 43 NSCLC patients. Patients provided written consent for the collection of tumor tissue at the time of surgery under an IRB approved protocol. Each tissue sample was split into 2 pieces, creating biological replicates for each tissue format. For each patient, RNA was extracted from 4 tissue pieces (2 FF, 2 RNAL), followed by microarray-based genomic profiling (Affymetrix U133 Plus 2.0). The 15-gene signature was applied to each profile, generating a numerical risk score and a risk category (high, low) using methods previously established (Zhu 2010 J Clin Oncol). The level of agreement was evaluated within biological replicates of each tissue format, as well as between the averaged biological replicates of matched FF and RNAL tissues. Results: The concordance in risk category between averaged biological replicates of matched FF and RNAL tissues was 84%, with a Pearson correlation of 0.74. This level of agreement is comparable to the inherent reproducibility of the assay observed within biological replicates of FF tissue, which demonstrated concordance of 79% and Pearson correlation of 0.83. In addition, a statistical in silico simulation was used to demonstrate that if the risk scores in this study had spanned the full dynamic range of the assay while maintaining the same level of inherent reproducibility observed in the current study, the level of concordance would be 89% with a Pearson correlation of 0.93. Conclusions: The level of agreement between matched FF and RNAL tissues is not inferior to that seen within FF biological replicates. Therefore, the 15-gene signature maintains its performance when used in RNAlater-preserved NSCLC tissues.
REINFORCE: A randomized trial of resistance training in patients with radically treated respiratory cancer.
Authors: Surmont Veerle F , Salhi Bihiyga , Haenebalcke Christel , Bogerd Sylvia Perez , Nguyen Dang Delphine M , Colman Roos , Ninane Vincent , Vermaelen Karim Y , Malfait Thomas , Van Maele Georges , Derom Eric , Van Meerbeeck Jan P. 
Published: March 2020

7541 Background: Limited evidence suggest that patients (pts) with respiratory cancer improve their post-radical treatment (PRT) exercise capacity (EC) and quality of life (QoL) by rehabilitation (REH). Whole body vibration (WBV) is proposed as an alternative to conventional resistance training (CRT). REINFORCE investigates the effect of 2 supervised resistance training programs on functional and maximal EC and QoL, measured by resp. 6 minutes walking distance (6MWD), Wmax and EORTC-QLQ-C30 physical functioning (PF). Methods: Consecutive pts with cI-IIIB (N)SCLC or cI-II mesothelioma were evaluated before (M1) and after (M2) completion of either surgery (S) +/- platin-based chemotherapy (PCT) and postop. radiotherapy (RT) or RT +/- PCT, and then randomized to usual care (UC) or 38 sessions of either CRT or WBV. After stratification for COPD, S, PCT and center, 6MWD (primary endpoint), Wmax and PF were measured at M1, M2 and after 12 weeks (w) of REH (M3). Minimal clinical important difference in 6MWD is 54 m, in Wmax 10 Watt and in PF +9 points. Mean changes are compared within and in-between the intention-to-treat intervention groups using linear regression models. Results: 70 pts were randomized with balanced M1-characteristics: UC 24; CRT 24; WBV 22; male 73%, median age 62 y(29-79); median BMI 25 kg/m²(16-42); COPD 40%; NSCLC 91%; stage I-II 60%. 48% had S and 6% RT as sole therapy, 46% a combination of S or RT with PCT and/or PORT; pneumectomy in 19%. A median of 28 CRT-sessions (10 – 36) and 23 WBV-sessions (0 – 37) were attended with a median M2-M3 interval of 14 w (9-30). M2-M3 change in 6MWD is 95 m (58-132) in CRT (p<.0001), 37m (-1-76) in WBV (p =0.06), 1 m(-34-36) in UC and is significantly higher with CRT than with WBV (p value vs. UC 0.0006 and 0.16, resp.) and highest in CRT-pts without COPD (133 m (86-181), p< 0.0001). M3 values did not significantly exceed M1 with either intervention. M2-M3 change in Wmax significantly improved with 15 Watt (6-24) in both CRT and WBV(p= 0.002). M2-M3 PF increased 6 points (-1–14) in CRT (p= 0.1) and 8 points (0–16) in WBV (p=0.04). Conclusions: In pts with respiratory cancer, PRT REH is recommended, with CRT significantly improving functional and maximal EC and WBV increasing maximal EC and PF. Clinical trial information: NCT00752700.
The potential role of lung cancer screening in lung cancer survivors.
Authors: Varlotto John M. , Yao Nengliang , Mahraj Rickhesvar , Recht Abram , Flickinger John Charles , Belani Chandra Prakash , Toth Jennifer , Reed Michael , Sciamanna Chris , Gilbert Christopher , Ali Suhail M. , DeCamp Malcolm M. 
Published: March 2020

7553 Background: The National Lung Screening Trial demonstrated improved overall survival (OS) and lung cancer specific survival (LCSS) in the 55-74-year-old age group, likely due to finding early-stage lung cancer. Patients with a past history of lung cancer were excluded from this trial. The purpose of investigation is to assess whether there is an increasing frequency of second lung cancers and whether the first primary reduces survival in a proposed screening population with Stage I (tumor size <4cm) NSCLC (survivor population, SP) as compared to similar patients presenting with their first lung cancer (new patients, NP). Methods: The SEER databases were used to investigate incidence (1973-2009) and OS/LCSS (1998-2009) of secondary lung cancer. Incidence was examined by frequency analysis and trend analysis. A SP was chosen who was originally treated definitively for Stage I-III NSCLC and survived at least four years after diagnosis (N=515). They were compared to NP who were presenting with their first lung cancer (N = 21,040). OS/LCSS in NP and SP with Stage I NSCLC were analyzed by Kaplan-Meier estimation, log-rank tests, and multivariate proportional hazards modeling. Results: The annual incidence rate/100,000 for secondary lung cancer has increased almost 5-fold in last 36 years (2.5 in 1973; 12 in 2009; p<0.001), more so in male patients. OS was not significantly different between NP and SP after accounting for treatment, tumor, and patient characteristics (male, HR=1.111, p=0.330; female, HR=0.840, p=0.118). Multivariate analyses show that LCSS was significantly better in SP females than for NP females (HR=0.849, p=0.025) but did not differ for males (HR=0.923, p=0.388). In the SP, OS decreased significantly with less aggressive treatment compared to lobectomy as the reference treatment (sub-lobar resection, HR=1.841, p=0.009; radiation, HR=2.351, p=0.002; observation, HR=2.145, p=0.016). Patient and tumor characteristics of the first lung cancer diagnosis were not significantly linked to OS. Conclusions: NP and SP diagnosed at Stage I had similar survival rates. The SP group also benefitted from increasingly aggressive treatment. Screening for lung cancer might be of benefit to lung cancer survivors.
Long-term results of a phase II trial of S-1 and cisplatin with concurrent thoracic radiotherapy for locally advanced non-small cell lung cancer.
Authors: Ohyanagi Fumiyoshi , Yamamoto Nobuyuki , Horiike Atsushi , Horai Takeshi , Kozuka Takuyo , Murakami Haruyasu , Harada Hideyuki , Takahashi Toshiaki , Nakamura Yukiko , Nishio Makoto 
Published: March 2020

7556 Background: Concurrent chemoradiotherapy is the standard treatment for unresectable stage III non-small cell lung cancer (NSCLC). S-1 has been shown to be significant efficacious for treating advanced NSCLC. Our previous phase II study reported short-term outcomes of cisplatin (CDDP)/S-1 chemoradiotherapy. Because CDDP/S-1 chemoradiotherapy is considered to have advantages over others in overall survival (OS) and toxicity, we analyzed its long-term outcomes by following up patients included in the phase II study. Methods: Forty-eight patients (aged <75 years) with unresectable stage III NSCLC were evaluated. They were treated with CDDP (60 mg/m2 on day 1) intravenously and oral S-1 (40 mg/m2 twice daily on days 1–14); this regimen was repeated every 4 weeks for four cycles. A 60-Gy thoracic radiation dose was delivered in 30 fractions beginning on day 2. Results: After a median follow-up of 6.3 years (range, 5.7–7.4 years), the median OS was 2.8 years [95% confidence interval (CI); 1.04–4.63 years], and the 3- and 5-year OS rates were 49.7% (95% CI: 35.6%–63.8%) and 33.0% (95% CI: 20.0%–46.6%), respectively. Out of the several variables evaluated as predictors of OS, including gender, age, stage, histology, and performance status (PS), only PS proved to be a statistically significant predictor in both univariate and multivariate analyses. Conclusions: CDDP/S-1 concurrent thoracic radiotherapy is clinically feasible and highly efficacious. Despite our relatively small sample size, the benefits of this regimen revealed in this study warrant further research.