bluuebunny/crossref_metadata_2025_split huggingface dataset:
CDKN2A-deletion to predict relapse in adult B-cell acute lymphoblastic leukemia (B-ALL).
Authors: Singh Preet Paul , Ketterling Rhett , Litzow Mark Robert , Tefferi Ayalew , Patnaik Mrinal M. , Pardanani Animesh Dev , Hogan William J. , Letendre Louis , Elliott Michelle A. , Begna Kebede , Wolanskyj Alexandra P. , Al-Kali Aref 
Published: March 2020

6614 Background: CDKN2A locus on chromosome 9p21 is implicated in altered molecular pathways leading to leukemogenesis as a tumor suppressor by inhibiting the proliferative kinases CDK4/CDK6 and blocking the cell-cycle division during G1/S phase. Deletion of CDKN2A locus is frequently seen in ALL, although prognostic significance remains unclear. Methods: Retrospective chart review at Mayo Clinic between 8/2005-11/2011 was performed on adult B-ALL patients (pts) who underwent fluorescent in situ hybridization (FISH) studies at diagnosis. Survival estimate was calculated using Kaplan-Meier statistics. Event-free survival (EFS) was defined as time between diagnosis and induction failure, relapse, or death, while overall survival (OS) as time between diagnosis and death Results: Out of 27 pts who had FISH studies for CDKN2A, 15 (56%) pts had CDKN2A deletions (8 homozygous/7 hemizygous), while 12 (44%) pts had diploid cytogenetics (none had abnormalities of MLL, bcr/abl fusion or CDKN2A deletion on FISH). There was no significant difference in median age, gender, WBC, hemoglobin, platelet count, LDH or complete remission (CR) rate (p=0.924) between the two groups. CDKN2A-deleted pts had higher circulating blasts (34% vs 16%, p=0.017). Of 13 CDKN2A-deleted pts, chromosome 9p was intact in 9 (69%) pts using routine cytogenetics. In the CDKN2A-deleted group, allogeneic stem cell transplant (ASCT) was performed in 7 (47%) pts at first CR and 1 at second CR. Four of 15 (27%) CDKN2A-deleted pts also had bcr/abl fusion. Five-year EFS was poorer in CDKN2A-deleted pts compared to normal FISH group (22% vs 60%, p=0.042), while 5-year OS was 72% vs 60% (p=0.308), respectively. Excluding the 4 bcr/abl fusion pts, 5-year EFS was still statistically significant (p=0.008). In the CDKN2A deleted group, both 5-yr EFS (80% vs 0%, p=0.006) and OS (100% vs 42%, p=0.016) were significantly superior in pts who received ASCT. Conclusions: CDKN2A deletions predict earlier relapse in pts with B-ALL. Majority of 9p abnormalities were only found by FISH testing and missed by conventional cytogenetics. In CDKN2A deleted pts, ASCT gave overall survival advantage. Further investigation through larger cohorts of pts is needed to validate these findings.
A seasonal pattern of presentation in younger patients with de novo acute myeloid leukemia (AML).
Authors: Drapkin Benjamin Jacob , Sadrzadeh Hossein , Brunner Andrew Mark , Werner Lillian , Babirak Loren , Attar Eyal C. , Ballen Karen K. , McAfee Steven L , Amrein Philip C. , Chen Yi-Bin Albert , Stone Richard M. , Fathi Amir Tahmasb 
Published: March 2020

6617 Background: Seasonal variation in AML has been studied in a wide variety of populations and locations, with primarily negative results. These investigations may have been undermined by the heterogeneity of the disease, as de novo and secondary AML can vary in disease presentation and trajectory, likely reflecting distinct pathogenesis.We investigated seasonal variation in the incidence of AML diagnosed at Massachusetts General Hospital (MGH) from 1992 through 2011, focusing on de novo disease among younger patients. Methods: We assembled a database of 511 biopsy-proven cases of adult-onset AML (age > 18 years), from the MGH electronic medical record, using a systematic search algorithm with IRB approval. We subdivided this database into three cohorts: (1) de novo AML diagnosed prior to age 50 (2) de novo AML diagnosed after age 50, and (3) secondary AML, preceded by chemotherapy, myelodysplasia or myeloproliferative disease. Diagnosis dates were grouped into quarters (Jan-Mar, Apr-Jun, Jul-Sep, Oct-Dec). Divergence of quarterly incidence from a null hypothesis of uniformity was evaluated by chi square analysis. Results: Among patients under 50-years-old with de novo AML, we found a 44% increase in incidence between October and December (Table, p=0.04). There was no significant variation throughout the rest of the calendar year. Furthermore, the incidence of both de novo AML diagnosed after age 50 and secondary AML conformed to a uniform quarterly distribution. As expected, the majority of AML patients under age 50 demonstrated intermediate-risk cytogenetics, most frequently normal karyotype. Conclusions: We found a significantly increased incidence of de novo AML in younger patients between the months of October and December, diagnosed at MGH from 1992 through 2011. This may reflect a local environmental or infectious exposure that is not relevant to the pathogenesis of AML in older patients or those in whom AML develops due to prior therapy or previous hematological disorder. Investigation of this exposure is ongoing. [Table: see text]
Preliminary safety and efficacy of ruxolitinib in patients (pts) with primary and secondary myelofibrosis (MF) with platelet counts (PC) of 50–100x109/L.
Authors: Talpaz Moshe , Hamburg Solomon I. , Jamieson Katarzyna , Terebelo Howard R. , Afrin Lawrence , Winton Elliott F. , Scola Michael A. , Lyons Roger M. , Harvey Jimmie Huling , Holmes Chris E. , Ortega Gregory L. , Prchal Josef T. , Silver Richard T. , Baer Maria R. , Erickson-Viitanen Susan Kay , O'Neill Peter , Peng Wei , Leopold Lance , Kantarjian Hagop , Verstovsek Srdan 
Published: March 2020

6630 Background: Ruxolitinib (RUX) has demonstrated clinical benefit as therapy for MF. This study explores the safety and efficacy of RUX in pts with MF and low PC, where clinical data are limited. Methods: In this phase II study, pts with intermediate-1 to high-risk MF, and PC of 50–100x109/L started RUX at 5 mg BID. Doses could be increased in 5 mg QD increments every 4 weeks (wks) beginning at wk 4. Doses were decreased or held for PC <35x109/L and <25x109/L respectively. Assessments: Total Symptom Score (TSS, using the modified MF Symptom Assessment Form v2.0, and comprised of scores from 0=absent to 10=worst imaginable for night sweats, itching, bone/muscle pain, early satiety, abdominal discomfort and pain under left ribs); Patient Global Impression of Change (PGIC, a 7-point scale ranging from “very much improved” to “very much worse”); spleen size by palpation and by MRI (data not yet available); and safety. Results: At the time of analysis, 23 pts had completed ≥4 wks on study. At baseline: mean PC=72x109/L; high (4%), intermediate-2 (52%) and intermediate-1 (44%) risk group; mean spleen length=16.6 cm; mean TSS=25.5. At the time of analysis, 4%, 40%, 26%, 26% and 4% of pts were receiving RUX 5 mg QD, 5 mg BID, 5 mg AM/10 mg PM, 10 mg BID, and 10 mg AM/15 mg PM, respectively. At wk 4 (all pts on 5 mg BID), mean TSS improved 14%; 13% had ≥50% improvement. At wk 8 (52% on 5 mg AM/10 mg PM), mean TSS improved 23%; 30% had ≥50% improvement. Mean spleen length reduction of 22% (wk 4) and 27% (wk 8) was observed, and PGIC scores of “much improved” or “very much improved” were reported in 35% (wk 4) and 39% (wk 8) of pts. There were no Grade 4 PC, no dose holds for AEs and no discontinuations; 1 pRBC transfusion-dependent pt had Grade 4 anemia. Three pts experienced a total of 4 SAEs (fever; hypnagogic dreams; and spleen pain/pneumonitis) which resolved while on treatment. Conclusions: Effects on spleen size, PGIC, and TSS, even over the first weeks at low doses, are superior to those observed in the placebo group in the COMFORT-I study. These preliminary findings suggest a dosing strategy starting with 5 mg BID RUX with subsequent dose optimization may be efficacious and well tolerated in MF pts who have low platelets.
GILT study: Oral vinorelbine (NVBo) and cisplatin (P) with concomitant radiotherapy (RT) followed by either consolidation (C) with NVBo plus P plus best supportive care (BSC) or BSC alone in stage (st) III non-small cell lung cancer (NSCLC): Final results of a phase (ph) III study.
Authors: Huber Rudolf M. , Engel-Riedel Walburga , Kollmeier Jens , Andreas Stefan , Staar Susanne , Klautke Gunther , Fietkau Rainer , Vaissiere Nathalie , Osowski Susanne , Flentje Michael 
Published: March 2020

7001 Background: Concurrent chemo-radiotherapy (CT-RT) is considered as a standard in st III NSCLC. Published trials with C after CT-RT show encouraging but discordant results. This ph III was set up to assess C in st III NSCLC. Methods: Patients (pts) received NVBo 50 mg/m² D1, D8, D15 + P 20 mg/m² D1-D4 q4w / 2 cycles (cy) + RT (66 Gy / 33 Fr). C for OR+SD pts: NVBo 60-80 mg/m² D1D8 + P 80 mg/m² D1 q3w / 2 cy + BSC (Arm A) or BSC (Arm B). PFS was the primary endpoint. Results: From 07/05 to 05/09, 279 pts received CT/RT and 201 pts (72%) were randomised to receive CT+BSC or BSC as C. Toxicity (tox) G3-4 (% pt) CT-RT/ C (Arm A/B): anaemia 3.2/3.5/1.1; thrombopenia 2.5/1.2/0.6; neutropenia (N) 11.2/11.7/5.7; febrile N 1.4/1.0/0; nausea (G3) 5.0/4.7/2.9; vomiting (G3) 3.9/3.5/2.0; anorexia 3.6/1.2/3.0; dysphagia 1.8/2.3/1.0; fatigue 3.3/ 2.3/1.0; pneumonia/ pneumonitis 2.6/0/2.0; CT-RT pain 2.2; CT-RT oesophagitis 8.6; 3 toxic deaths. Conclusions: In this ph III, NVBo+P+RT reports a high level of efficacy (OR 60.7%; DCR 86.0%) and low tox. The DCR is significantly improved in pts who received C with NVBo+ P in eval pts (p=0.0084). Lung tox was not enhanced by using NVBo+P as C. However no survival advantage for C was achieved. [Table: see text]
A phase III study comparing amrubicin and cisplatin (AP) with irinotecan and cisplatin (IP) for the treatment of extended-stage small cell lung cancer (ED-SCLC): JCOG0509.
Authors: Kotani Yoshikazu , Satouchi Miyako , Ando Masahiko , Nakagawa Kazuhiko , Yamamoto Nobuyuki , Ichinose Yukito , Ohe Yuichiro , Nishio Makoto , Hida Toyoaki , Takeda Koji , Kimura Tatsuo , Minato Koichi , Yokoyama Akira , Atagi Shinji , Shibata Taro , Fukuda Haruhiko , Tamura Tomohide , Saijo Nagahiro ,   Japan Clinical Oncology Group
Published: March 2020

7003 Background: IP is the standard treatment for ED-SCLC, however often cause severe diarrhea. AP have shown promising activity in SCLC with fewer diarrhea. We conducted a phase III trial comparing AP with IP. Methods: Eligibility criteria included patients (pts) with chemotherapy-naïve, ED-SCLC, aged 20 to 70, and ECOG PS 0-1. Pts were randomized to receive either IP or AP, balancing for site, sex, and PS. IP comprised administration of I (60 mg/m2) iv on days 1, 8, and 15, and P (60 mg/m2) iv on day1,every 4 weeks. AP comprised administration of A (40 mg/m2) iv on day 1-3, and P (60 mg/m2) iv on day1, every 3 weeks. The planned sample size was 141 pts in each arm with a one-sided alpha of 5% and power of 70% and a non-inferiority margin of hazard ratio (HR) as 1.31. The primary endpoint was overall survival (OS). The secondary endpoints were response rate (RR), progression-free survival (PFS), adverse events (AEs), and quality of life (QOL). We evaluated pts’ QOL twice: at the baseline and after completion of the second course. Results: 284 pts were randomized to IP (n=142) and AP (n=142). Median age was 63, 84% were male, and 56% had PS 0. When 191pts enrolled, more febrile neutropenia (FN) was observed in AP than anticipated, and the initial dose of A was decreased from 40 mg/m2 to 35 mg/m2. At the second interim analysis conducted after the completion of patient accrual, the median OS of AP (15.0 m) was much worse than that of IP (18.3 m) and the HR (1.41; 96.3% CI, 1.03-1.93) exceeds even the non-inferiority margin, so the Data and Safety Monitoring Committee recommended early publication of the results. Median PFS was 5.7 (IP) vs. 5.2 months (AP) (HR 1.43, 95% CI, 1.13-1.82). RR was 69.5% (IP) vs. 77.9% (AP) (p=0.14). AEs in IP and AP arm were Grade 4 neutropenia (22.5% vs. 78.6%), G3-4 FN (10.7% vs. 32.1%), and G3-4 diarrhea (7.1% vs.1.4%). Proportion of improvement in physical status of QOL was 37.1%(IP) vs. 31.7%(AP), (odds ratio 0.72; 95%CI, 0.43-1.22; P=0.227). Conclusions: AP showed more bone marrow suppression than expected although it caused less diarrhea. The non-inferiority of AP to IP was not demonstrated and IP remains the standard treatment for ED-SCLC.
The SELECT study: A multicenter phase II trial of adjuvant erlotinib in resected epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC).
Authors: Neal Joel W. , Pennell Nathan A. , Govindan Ramaswamy , Lanuti Michael , Rosovsky Rachel Pam Greenerger , Heist Rebecca Suk , Shaw Alice Tsang , Temel Jennifer S. , Muzikansky Alona , Janne Pasi A. , Lynch Thomas James , Azzoli Christopher G. , Sequist Lecia V. 
Published: March 2020

7010 Background: Cancers with activating EGFR mutations are exquisitely sensitive to EGFR tyrosine kinase inhibitors (TKIs) and retrospective data suggests adjuvant TKIs may improve outcomes in EGFR mutants. This prospective trial investigates the safety and efficacy of adjuvant erlotinib in EGFR mutation-positive NSCLC. Methods: Patients (pts) with surgically resected stage IA-IIIA NSCLC harboring activating EGFR mutations were treated with 150 mg/day of erlotinib for 2 years (y) after completion of any standard adjuvant chemotherapy and/or radiotherapy. The trial was designed to enroll 36 patients, and powered to demonstrate a primary endpoint of 2 y disease free survival (DFS) exceeding 85%, which would suggest improvement over the historically expected 70% 2 y DFS in early stage EGFR-mutant NSCLC (J Thorac Oncol 6:569). Results: Thirty-six pts were enrolled at five sites between 1/08 and 11/09; 53% stage I; 19% stage II; 28% stage IIIA. Toxicities were typical of erlotinib; no grade 4 or 5 events or pneumonitis occurred. 8 pts (22%) required one dose reduction to 100 mg/day and 5 (14%) two reductions to 50 mg/day for grade 3 or persistent grade 2 toxicities. 11 pts discontinued before 2 full years (<1 month (mo) [4], 1-12 mo [2] and 12-23 mo [5]) for toxicities [6], patient preference [3], prostate cancer [1] and recurrence [1]. After a median follow-up of 2.5 y, the 2 y DFS from enrollment is 94% (95% CI 80%, 99%). 10 patients have recurred, 1 during erlotinib treatment and the others after stopping erlotinib (interval before recurrence 2 mo [1], 6-12 mo [4], >12 mo [4]). Genotyping on repeat biopsies from seven of the recurrent cases is underway, as is assessment of response to subsequent erlotinib therapy. Two pts have died of recurrence: one at 1.5 y who stopped erlotinib after 1 mo for toxicity, and one at 2 y who progressed while on erlotinib. Conclusions: This is the first prospective study to report the efficacy of adjuvant erlotinib in NSCLC pts with EGFR mutations. This approach is feasible and yields excellent 2y DFS compared to historical genotype-matched controls. This trial was subsequently expanded to 100 pts to permit subgroup analysis by stage.
Updated results of a phase III trial comparing standard thoracic radiotherapy (RT) with or without concurrent daily low-dose carboplatin in elderly patients (pts) with locally advanced non-small cell lung cancer (NSCLC): JCOG0301.
Authors: Okamoto Hiroaki , Atagi Shinji , Kawahara Masaaki , Yokoyama Akira , Yamamoto Nobuyuki , Ohe Yuichiro , Sawa Toshiyuki , Shinkai Tetsu , Mori Kiyoshi , Takeda Koji , Harada Masao , Nakagawa Kazuhiko , Yoshimura Naruo , Tomizawa Yoshio , Takeda Yuichiro , Fukuda Haruhiko , Shibata Taro , Ishikura Satoshi , Saijo Nagahiro , Tamura Tomohide ,   Japan Clinical Oncology Group (JCOG)
Published: March 2020

7017 Background: We previously reported the superiority of combined chemo-radiotherapy (CRT) over RT alone in elderly pts with locally advanced NSCLC (Atagi et al. ECCO2011). One and a half years follow-up data from last accrual are presented. Methods: Pts older than 70 years with unresectable stage III NSCLC were randomized to either RT alone (RT arm), a total dose of 60 Gy, or CRT arm including the same RT plus concurrent chemotherapy with carboplatin 30 mg/m2/day, 5 days/week × 20 days. The primary endpoint was overall survival (OS). The planned sample size was 100 pts in each arm with one-sided alpha of 5% and 80% power to detect a difference in median survival time (MST) from 10 months in RT arm to 15 months in CRT arm. Results: Between Sep 2003 and May 2010, 200 pts were randomized. Baseline characteristics were similar in the RT (n=100) vs CRT (n=100) arms: median age, 77 vs 77 years; stage IIIB (n), 46 vs 49; PS 0/1/2 (n), 41/55/4 vs 41/56/3. The second planned interim analysis was performed 10 months after the completion of accrual. In accordance with the pre-specified stopping rule, the JCOG Data and Safety Monitoring Committee recommended early publication of this trial because of the difference in OS favoring the CRT arm. In the updated analysis, OS was better in the CRT arm than the RT arm (HR = .64, 95% CI = .46-.89, one-sided p = .0033 by stratified log-rank test). In each arm (RT/CRT), MST was 16.5 mo/22.4 mo with 3-year OS of 14.3%/34.6%, response rate of 44.9%/54.6% (p=.201) and median progression-free survival of 6.9 mo/8.9 mo (p=.003). Gr 3/4 toxicities were (RT/CRT): neutropenia 0%/57.3%, infection 4.1%/12.5%, dysphagia 0%/1.0%, late RT toxicities 7.4%/7.5%. The pattern of relapse site and post-protocol treatment were almost similar between the arms. Even after an adjustment by the Cox regression analysis with six variables [stage, PS, sex, age, histology, smoking status], CRT arm showed better survival (HR=.71, p=.038). Conclusions: The CRT using daily carboplatin is considered to be the standard treatment for elderly pts with locally advanced NSCLC.
SWOG S0533: A pilot trial of cisplatin (C)/etoposide (E)/radiotherapy (RT) followed by consolidation docetaxel (D) and bevacizumab (B) (NSC-704865) in three cohorts of patients (pts) with inoperable locally advanced stage III non-small cell lung cancer (NSCLC).
Authors: Wozniak Antoinette J. , Moon James , Thomas Charles R. , Kelly Karen , Mack Philip C. , Gaspar Laurie E. , Raben David , Pandya Kishan J. , Gandara David R. ,   Southwest Oncology Group
Published: March 2020

7018 Background: Bevacizumab combined with chemotherapy has improved survival in the treatment of advanced NSCLC. This pilot trial was conducted to determine if bevacizumab could be incorporated into the standard chemotherapy/RT for locally advanced NSCLC. Methods: Pts with unresectable stage III NSCLC, PS 0-1, and adequate organ function were eligible. Pts were accrued in two strata, low and high risk (squamous histology, hemoptysis, tumor with cavitation or near a major vessel). Pts were treated with C 50mg/m2 (d 1 and 8), E 50mg/m2 (d 1-5) for 2 cycles concurrent with RT (64.8 Gy at 1.8 Gy/fx for 36 fxs) followed by consolidation D 75mg/m2 and B 15 mg/kg for 3 cycles (Cohort 1). If safety was established then accrual would continue to Cohort 2 (B, d 15, 36, 57) and then Cohort 3 (B d 1, 22, 43). Results: 29 pts (17 Low, 12 High) were registered, all to Cohort 1. 26 pts (stage IIIB 19 pts, squamous 4 pt, adenosquamous 1 pt) were evaluable. 25 completed chemo/RT. Grade 3/4 toxicities during chemo/RT included: neutropenia 10 pts, thrombocytopenia 2, anemia 2, febrile neutropenia 3, esophagitis 2, pneumonitis 1. 21 were assessed for safety with D/B consolidation. The major adverse events during D/B consolidation were pneumonitis (Gr 3 - 2 pt) and 2 episodes of fatal hemoptysis in the high risk group resulting in closure of this stratum. The low risk stratum subsequently closed because of poor accrual. Median overall survival was 23 mos for low risk pts and 17 mos for the high risk stratum. Conclusions: In this trial, bevacizumab could not be successfully integrated into chemo-radiation for stage III NSCLC, particularly in pts considered at high risk for hemoptysis. The trial suffered from several temporary closures as mandated by CTEP when new bevacizumab-related toxicities were reported, contributing to slow accrual. In lower risk pts the data are insufficient to determine safety or efficacy. Supported in part by the following PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute, DHHS: CA32102 and CA38926.
A randomized, multicenter phase II study investigating additional weekly cetuximab to concurrent chemoradiotherapy in locally advanced non-small cell lung carcinoma: Reporting on the efficacy.
Authors: van den Heuvel Michel M , Vincent Andrew D. , Uyterlinde Wilma , Aerts Joachim , Koppe Fredirike , Codrington Henk , Kunst Peter W.E. , Dieleman Edith , van de Vaart Paul , Verheij Marcel , Belderbos Jose 
Published: March 2020

7019 Background: Modest benefits from concurrent chemoradiotherapy (CRT) in patients with locally advanced NSCLC warrant more effective treatment regimen. Cetuximab, a monoclonal antibody against the epidermal growth factor receptor has shown activity in NSCLC. Feasibility data and toxicity have been published previously. We report treatment outcome of a multicenter phase II study of the combination of high dose accelerated RT and daily dose cisplatin with or without weekly cetuximab. Methods: Patients with locally advanced NSCLC received accelerated RT (66 Gy in 24 fractions) and concurrent daily cisplatin (6 mg/m2) with (Arm A) or without (Arm B) additional weekly cetuximab (400 mg/m2 loading dose one week prior to the RT start followed by weekly 250 mg/m2). The Objective Local Response Control (OLRC) was determined at 6 and 24 weeks after treatment using response evaluation criteria in solid tumours criteria. Results: Between Feb 2009 and May 2011, 102 patients were included. Median follow-up was 13 months. Patients and tumor characteristics are shows in the Table. Stage distribution was: II (8%), IIIa (51%), and IIIb (40%). The CRT was well tolerated. The OLRC at 24 weeks was 79% in Arm A and 80% in Arm B. The one-year progression free survival and overall survival were 58% (45%-76%) and 76% (64%-91%) for Arm A and 49% (35%-68%) and 72% (58%-89%) for Arm B respectively. Conclusions: The addition of cetuximab to low dose cisplation CRT does not improve OLRC in an unselected patient cohort but data on longterm disease control and survival are to be awaited. [Table: see text]