bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health-related quality of life (HRQoL) and symptom burden in patients (Pts) with myelofibrosis (MF) in the COMFORT-II study.
Authors: Kiladjian Jean-Jacques , Gisslinger Heinz , Passamonti Francesco , Niederwieser Dietger , Mendelson Estella , Sirulnik L. Andres , Copley-Merriman Kati , Zhou Xiaolei , Levy Richard S. , Knoops Laurent , Cervantes Francisco , Barbui Tiziano , Barosi Giovanni , Vannucchi Alessandro M. , Harrison Claire N 
Published: March 2020

6626^ Background: Ruxolitinib has demonstrated rapid and durable reductions in splenomegaly and improved disease-related symptoms and QoL in 2 phase 3 studies (COMFORT-I and -II) in pts with primary MF (PMF), post-polycythemia vera-MF (PPV-MF), or post-essential thrombocythemia-MF (PET-MF). The prevalence of individual symptoms among these pts has not been defined. We evaluated the baseline HRQoL and symptoms among pts enrolled in COMFORT-II. Methods: COMFORT-II is a randomized, open-label, multicenter, phase 3 study comparing ruxolitinib with best available therapy. HRQoL and symptoms were assessed at baseline using the European Organisation for the Research and Treatment of Cancer QoL Questionnaire–Core 30 (EORTC QLQ‑C30) and Functional Assessment of Cancer Therapy–Lymphoma (FACT‑Lym); this analysis summarizes these scores for all pts, regardless of assigned treatment. Results: In COMFORT-II (N = 219), 52% of pts were aged > 65 years and 57% were male. By IPSS criteria (Cervantes et al. 2009), 40% had intermediate-2 and 60% had high-risk MF. Mean (95% CI) EORTC global health status/QoL (53.7 [50.6-56.7]; median, 50.0) and FACT-General total scores (73.0 [70.8-75.2]) were comparable to those for pts of similar age with other cancers (Oliva et al. 2011: median global health status score of 50 for acute myeloid leukemia [AML]). The most frequent symptoms (reported as “quite a bit” or “very much”) were fatigue (54%), dyspnea (30%), insomnia (30%), pain (29%), night sweats (23%), and itching (21%), and there were differences in baseline symptoms across MF subtypes (Table). Conclusions: This analysis shows that pts with MF experience severe disease-related symptoms and have diminished HRQoL similar to pts with AML, but because pts with MF have a longer life expectancy (an average of 2.3 to 4 years for high and intermediate-2 risk pts, respectively), they may suffer with a reduced QoL for many years. [Table: see text]
Post hoc analysis of association between treatment response and various indicators of efficacy and safety in a randomized phase III trial of decitabine in older patients with acute myeloid leukemia.
Authors: Minden Mark D , Arthur Chris , Mayer Jiri , Jones Mark M. , Tarassoff Peter G. , Kantarjian Hagop 
Published: March 2020

6627 Background: In a recent, large phase III trial (NCT00260832; Kantarjian, JCO; in press), 485 patients ≥65y with newly diagnosed acute myeloid leukemia (AML) received, every 4 wks, treatment choice (TC) of either supportive care or cytarabine (20 mg/m2 subcutaneous injection, 10 consecutive days) or decitabine (DAC) 20 mg/m2 (1-h intravenous [IV] infusion, 5 consecutive days). This post hoc analysis investigated relationships between response to treatment and indicators of efficacy and safety. Methods: Response was defined as morphologic complete remission (CR), or CR with incomplete blood count recovery (CRi) or partial response (PR). Transfusions (red blood cell [RBC] or platelets [PLT]), IV antibiotic use, and dose modifications were tabulated for responders and nonresponders to DAC or TC during the treatment period. Results: Fewer responders than nonresponders had dose modifications (30.4% vs 64.5%, respectively; P<.0001). Antibiotic use and transfusions were similar in both groups. Overall survival for responders was 16.1–18.5 mo vs 4.2–4.9 mo for nonresponders. Conclusions: These data suggest that response to DAC or TC treatment predicts clinically relevant benefits, with fewer dose modifications in older patients with newly diagnosed AML. The number of transfusions and antibiotic use was impacted by the longer survival time of responders vs nonresponders. Data on the impact of early response are being analyzed. [Table: see text]
Phase II study of short CHOP-rituximab combination with early consolidation with ibritumomab-tiuxetan-Y90 (IT-Y90) in non-pretreated patients age 65 to 80 with CD20+ diffuse large B-cell lymphoma (DLBCL).
Authors: Peyrade Frederic , Lepeu Gerard , Gal Jocelyn , Fruchart Christophe , Coso Diane , Bologna Serge , Provencio Mariano , Kaphan Regis , Sohn Claudine , Audhuy Bruno , Codina Gomez , Thyss Antoine 
Published: March 2020

6633 Background: IT-Y90was approved in follicular lymphoma, and some data indicates that it could be used in DLBCL. It has been reported that early TEP-TDM negativity is associated with a longer survival in DLBCL, which suggest that these patients could benefit of a less intensive protocol. Methods: We conducted an international, open-label, phase II non-randomised study, in patients aged between 65 and 80 with age-adjusted (aa) IPI score of 0 and 1 and CD20+ DLBCL. The primary objective was to evaluate the efficacy of 3 cycles of RCHOP14 followed by, in case of complete response (CR), an injection of IT-Y90. Results: Thirty patients (M/F= 1) were included. Median age was 72.6 years (range 65 - 80). Patients had a stage III/IV, elevated LDH and IPI=1 in 38%, 16.6 and 57% respectively. 25 patients received the full treatment. Five obtained an uncomplete FDG-PET response and were excluded after 2 RCHOP cycles. 23 patients received the full IT-Y90 dosage (0.4mCi/Kg) and two received the attenuated dosage (0.3mCi/Kg). Mean treatment time was 54 days (median 52; min 48-max 69). The CR rate after RCHOP treatment was 85% [95% CI: 65-94]. No treatment-related deaths occurred. Grade III-IV neutropenia and thrombocytopenia was observed in 45% and 4%, respectively. Five patients experienced at least one febrile neutropenia. After IT-Y90, mean duration time for platelets <50G/l was 2.08 weeks (median 2; min 0-max 5). Two patients required platelet transfusion. With a median follow-up of 29.5 months [95% CI: 23-39], the estimated 3-year PFS was 90% [95% CI: 80-100] and the 3-year OS was 100% [95% CI: 100-100]. Among patients treated with 90Y-IT, only 3 relapsed were recorded (at 6, 16 and 24 months). Conclusions: this study suggested the feasibility, and efficacy of a short regimen including one injection of IT-Y90for selected DLBCL in complete response after 3 cycles of RCHOP14. This results need to be confirmed by further studies.
Accuracy of FDG-PET to diagnose lung cancer in the ACOSOG Z4031 trial.
Authors: Grogan Eric L. , Deppen Stephen A , Ballman Karla V. , Andrade Gabriela Maria , Verdail Francys C , Aldrich Melinda C , Chen Heidi , Decker Paul A. , Harpole David , Cerfolio Robert , Keenan Robert , Jones David R , D'Amico Thomas A. , Shrager Joseph B , Meyers Bryan F , Putnam Joe B. 
Published: March 2020

7008 Background: Fluoro-deoxyglucose positron emission tomography (FDG-PET) is recommended for diagnosis and staging of known or suspected NSCLC. Meta-analyses examining the accuracy of FDG-PET to diagnose lung cancer demonstrated high sensitivity 94% and specificity 83% but were performed in select centers. The purpose of this study is to evaluate the accuracy of FDG-PET to diagnose NSCLC and examine enrolling site differences in the national prospective ACOSOG Z4031 trial. Methods: 1,074 patients with clinical stage I (cT1-2N0M0) known or suspected NSCLC were enrolled between 2004 and 2006 in the Z4031 study and underwent surgical resection. The final diagnosis was determined by pathological examination. FDG-PET results were abstracted from radiology interpretations included in the case report forms. FDG-PET avidity was categorized based on either radiologist description or reported maximum standard uptake value (SUV). The four categories were: not avid and not cancerous (SUV=0), low avidity and likely not cancerous (SUV>0 and <2.5), avid and probably cancerous (SUV>2.5 and <5) and highly avid and likely cancerous (SUV>5). Sensitivity analysis of FDG-PET diagnostic accuracy was performed for varying levels of avidity and by preoperative lesion size. Differences in accuracy by enrolling site were examined. Results: There were 51 enrolling sites in 39 cities with 969 eligible participants. Preoperative FDG-PET results were available for 682 participants. Lung cancer prevalence was 83%. FDG-PET sensitivity was 82% (95% CI: 79-85), and specificity was 31% (95% CI: 23-40). Positive and negative predictive values were 85% and 26%, respectively and accuracy improved with lesion size. There were 80 false positive scans and 69% were granulomas. False negative scans occurred in 101 patients (11were ≤10mm) with adenocarcinoma, squamous, bronchoalveolar cell and neuroendocrine tumors responsible for 64%, 12%, 10% and 8% of false negative results, respectively. Specificity did not differ between the 8 sites with >25 patients (p=0.74). Conclusions: In a national surgical population with clinical stage I NSCLC, FDG-PET to diagnose lung cancer performed poorly compared to published studies. Reasons for poor test performance should be explored.
Stages I-II non-small cell lung cancer treated using either lobectomy by video-assisted thoracoscopic surgery (VATS) or stereotactic ablative radiotherapy (SABR): Outcomes of a propensity score-matched analysis.
Authors: Senan Suresh , Verstegen Naomi E , Palma David , Rodrigues George , Lagerwaard Frank J , van der Elst A , Mollema R , van Tets W F , Warner Andrew , Joosten J J.A. , Amir M I , Haasbeek Cornelis J , Smit Egbert F , Slotman Ben J. , Oosterhuis J W 
Published: March 2020

7009 Background: VATS procedures are increasingly used in early-stage NSCLC. As high local control rates are also seen with stereotactic ablative radiotherapy (SABR), we performed a propensity score-matched analysistocompare loco-regional control (LRC) after both treatments. Methods: Patients with stage I-II NSCLC treated at 6 hospitals (1 university and 5 regional hospitals) with VATS lobectomy were eligible. Details of SABR patients were obtained from a single-institutional database. All VATS-lobectomies were performed in accordance with ESTS guidelines. Patients were matched using propensity scores based on cTNM, age, gender, Charlson comorbidity score, lung function and performance score. Matching was performed blinded to all outcomes. Excluded were: synchronous lung tumors, COPD GOLD class 4 or history of prior lung cancer. A total of 86 VATS- and 527 SABR patients were eligible for matching (1:1 ratio, caliper distance of 0.025 without replacement). Loco-regional failure was defined as recurrence in/adjacent to the radiation planning target volume or surgical margins, the ipsilateral hilum or mediastinum. Recurrences were either biopsy-confirmed or PET-positive and reviewed by a tumor board. Patients upstaged during VATS and those developing recurrence were treated in accordance with national guidelines. Results: The matched cohort consisted of 128 patients with cT1-3N0 NSCLC following SABR (n=64) or VATS-lobectomy (n=64). Median follow-up was 30 and 16 months, respectively. The groups were well matched on baseline variables. SABR patients had better LRC rates at 1- and 3-years (96.8% and 93.3% vs. 86.9% and 82.6%, respectively, p= .03). Three-year progression-free survival (PFS) did not significantly differ after SABR (79.3% versus 63.2%, p = .09). Distant recurrence rates and overall survival (OS) did not significantly differ. Conclusions: Although loco-regional control was superior after SABR compared to VATS-lobectomy, PFS and OS did not differ at this time-point. Our findings support the current randomized controlled trial evaluating both treatments (ACOSOG Z4099).
MAGE-A3 cancer immunotherapeutic in resected stage IB-III NSCLC patients with or without sequential or concurrent chemotherapy.
Authors: Pujol Jean-Louis , Vansteenkiste Johan F. , De Pas Tommaso Martino , Atanackovic Djordje , Reck Martin , Thomeer Michiel , Douillard Jean-Yves , Fasola Gianpiero , Potter Vanessa , Taylor Paul , Bosquee Lionel , Debois Muriel , de Sousa Alves Pedro , Louahed Jamila , Lehmann Frederic , Brichard Vincent G. 
Published: March 2020

7013 Background: Previous trials with the MAGE-A3 recombinant (rec) protein formulated with an immunostimulant have shown induction of specific immune responses and signals of clinical activity in different cancer diseases. In this phase I/II study (NCT 00455572), we evaluated the safety profile of the MAGE-A3 cancer immunotherapeutic (CI), formulated with the rec MAGE-A3 protein and the AS15 immunostimulant, and the induction of specific immune response with or without adjuvant chemotherapy (CT). Methods: MAGE-A3 CI was administered i.m. 8q3w in resected MAGE-A3+ stage IB-III NSCLC patients (pts). Three cohorts (C) were evaluated: Immunization with concurrent cisplatin plus vinorelbine (C1), sequentially after the same CT (C2) or with no CT (C3). The anti-MAGE-A3 humoral and cellular immune responses were evaluated by ELISA and intracellular cytokine staining (T cells producing both IFNg and TNF) respectively. Adverse Events (AEs) were graded according to CTCAE v. 3.0. Results: A total of 38/55 treated pts received the 8 doses schedule (15/19 in C1, 14/18 in C2, 9/18 in C3). Almost all pts reported at least one AE, mostly general constitutional disorders and administration site reactions. Six patients reported related grade 3 AEs. No related grade 4-5 AE or related SAE were reported. Immunogenicity results in the total treated population are reported in the table below. Conclusions: In this trial, patients in cohorts 2 and 3 correspond to the two populations enrolled in the Phase III MAGRIT trial evaluating the same MAGE-A3 CI. The phase I/II results suggest that this CI is well tolerated and induces in all treated pts specific antibodies against MAGE-A3 after 4 doses in presence or not of concurrent or sequential adjuvant CT. About 25% of the treated pts are considered as CD4 responders in presence or not of concurrent or sequential adjuvant CT. [Table: see text]
Comparison of prognostic impact between metabolic and radiologic response after induction chemotherapy for resectable malignant pleural mesothelioma: A multicenter study.
Authors: Tsutani Yasuhiro , Takuwa Teruhisa , Miyata Yoshihiro , Fukuoka Kazuya , Hasegawa Seiki , Nakano Takashi , Okada Morihito 
Published: March 2020

7031 Background: Induction chemotherapy followed by extrapleural pneumonectomy (EPP) for resectable malignant pleural mesothelioma (MPM) is controversial. To select optimal candidates for EPP, we evaluates the usefulness of metabolic response on fluorodeoxyglucose-positron emission tomography (FDG-PET) compared with radiologic response on high-resolution computed tomography (HRCT) after induction chemotherapy to predict prognosis for patients with resectable MPM who underwent EPP in the setting of multicenter study. Methods: We performed HRCT and FDG-PET before and after induction platinum-based chemotherapy on 50 patients with clinical T1-3 N0-2 M0 MPM who underwent EPP ± postoperative hemithoracic radiation. A decrease of more than 30% in tumor maximum standardized uptake value (SUVmax) was defined as a metabolic responder. Radiologic response using modified RECIST or metabolic response and surgical results were analyzed. Results: In all cohort patients, median overall survival (OS) from diagnosis was 20.5 month (95% confidence interval [CI], 15.0-26.0 month). Fourteen patients were classified as metabolic responders (28%) and 36 as non-responders (72%). Metabolic responders significantly correlated to OS with median OS for metabolic responders of not reached (3-year OS of 60.0%) versus 18.7 month (95% CI, 13.3-24.2 month, 3-year OS of 26.5%) for non-responders (P = .025). No correlation was observed between OS and radiologic response with median OS for radiologic responders of 25.7 month (n = 20, 95% CI, 14.5-37.0 month, 3-year OS of 35.8%) versus 17.7 month (n = 30, 95% CI, 12.8-22.6 month, 3-year OS of 35.1%) for non-responder (p = .216). Based on the multivariate Cox analyses, decreased SUVmax (%) (p = .010) was a significantly independent factor for OS as well as epithelioid subtype (p = .044). Conclusions: Metabolic response on FDG-PET has higher predictive value of prognosis than radiologic response on HRCT after induction chemotherapy for patients with resectable MPM. Patients with metabolic responder and/or epithelioid subtype can be good candidates for EPP after induction chemotherapy.
Epidermal growth factor receptor mutation status and adjuvant chemotherapy in resected advanced non-small cell lung cancer.
Authors: Wang Si-Yu , Sun Haibo , Ou Wei , Fang Qin 
Published: March 2020

7034 Background: Mutations in the epidermal growth factor receptor (EGFR) are associated with response to chemotherapy in patients with advance NSCLC. The purpose of this study was to assess the association of mutations in the EGFR tyrosine kinase domain and the efficacy of adjuvant chemotherapy in patients with fully resected IIIA-N2 NSCLC tumors. Methods: Tumor samples (n =150) from patients in our prior trial with IIIA-N2 NSCLC who either had or had not received paclitaxel/vinorelbine plus carboplatin chemotherapy following removal of the tumor were analyzed for EGFR mutations in exons 19 and 21. The association of the presence of EGFR mutations and survival following treatment was assessed. Results: Mutations were identified in 33 (22%) patients (n=13 in the no chemotherapy [observation] arm and n=20 in the chemotherapy arm). Fourteen patients (9.3%) had deletion mutations in exon 19, and 19 patients (12.7%) had a substitution mutation in exon 21. Compared with patients wild-type for EGFR, patients with EGFR mutations had numerical but not statistically significant improved disease-free survival (35 months [95% CI, 14.6-55.4] versus 23 months [95% CI, 17.3-28.7], respectively, P=0.339) and overall survival (36 months [95% CI, 27.9 to 44.1] versus 26 months [95% CI, 20.1 to 31.9], respectively p=0.271) regardless of treatment. Patients with wild-type EGFR had greater overall survival with chemotherapy compared to no adjuvant therapy (HR=1.920; 95%CI, 1.245-2.963; p=0.003). In contrast, EGFR mutant patients in the observation group compared to the chemotherapy group had longer median disease-free survival (35 months [95% CI, 20.9 to 49.1] versus 27 months [95% CI, 5.3 to 48.7], respectively, p=0.671) and overall survival (33 months [95% CI, 24.2 to 41.8] versus 40 months [95% CI, 31.8 to 48.2] respectively, p =0.360). Conclusions: In this study, the status of mutations in exons 19 and 21 of EGFR was associated with different clinical outcomes in patients with resected IIIA-N2 NSCLC tumors either treated with or without adjuvant chemotherapy. These findings suggest that a patient’s treatment should be customized to their EGFR mutational status.
A phase II study of cisplatin (P), S-1 (S), and concurrent thoracic radiotherapy (TRT) for locally advanced non-small cell lung cancer (LA-NSCLC): Okayama Lung Cancer Study Group trial 0501.
Authors: Kishino Daizo , Nogami Naoyuki , Segawa Yoshihiko , Aoe Keisuke , Ueoka Hiroshi , Takigawa Nagio , Harita Shingo , Tabata Masahiro , Tanimoto Mitsune , Kiura Katsuyuki ,   Okayama Lung Cancer Study Group
Published: March 2020

7042 Background: We previously reported an efficacy and safety of fractionated schedule ofP and docetaxel (D) (days 1, 8, 29, and 36, each) and concurrent TRT (DP-TRT) for LA-NSCLC (JCO 2010). Although the median survival time (MST: 26.3 months) was excellent, grade 3 or greater pneumonitis (10%) and esophagitis (14%) were observed and treatment-related death was 3%.Thus, further improvement in the safety as well as efficacy is strongly warranted. S, an oral fluoropyrimidine, is a new active agent possessing a radio-sensitizing effect. Additionally, combining S and P offered an active and safe regimen for metastatic NSCLC. The objective of this study was to assess the efficacy and safety of S + P with concurrent TRT for LA-NSCLC. Methods: Patients with stage IIIA/IIIB, aged ≤75 years and PS 0-1, and without any prior chemotherapy were eligible for this study. Patients were treated with P (40 mg/m² on day 1, 8, 29 and 36) and S (40 mg/m²/dose b.i.d. on days 1-14 and 29-42) and TRT (60 Gy/30 fr over 6 weeks starting on day 1). Primary endpoint was response rate (RR), and required sample size was 48 patients. Results: Between 2006 and 2009, 48 patients were enrolled (37 men; median age, 66 years; PS 0/1, 36/14; IIIA/IIIB, 23/25; sq/non-sq, 22/26). Partial response was observed in 37 patients (77%; 95% confidence interval: 63-88%). The response rate was higher in older patients (≥65 yrs) than younger (<65 yrs) (89% vs. 64%, p=0.041). At a median follow-up of 40 months, median progression-free survival and MST were 9.3 months and 31.3 months, respectively. No difference in efficacy (response and survivals) was observed stratified by histology (sq vs. non-sq). Toxicities were generally mild, including G3/4 neutropenia (44%), G3/4 thrombocytopenia (13%), G3 febrile neutropenia (8%) and G3 pneumonitis (4%). No one developed Gr3/4 esophagitis. No toxic deaths occurred. Conclusions: This chemoradiotherapy regimen yielded a favorable overall survival data. Also, it was well-tolerated in patients with LA-NSCLC as compared with concurrent DP-TRT therapy especially in term of TRT-related toxicities. A phase III trial of this regimen vs. DP-TRT is now planned.
Would screening benefit 75- to 84-year-old patients with non-small cell lung cancer (NSCLC)?
Authors: Lake Jessica , Flickinger John Charles , Varlotto John M. , Recht Abram , DeCamp Malcolm M. , Belani Chandra Prakash , Mackley Heath B. , Sciamanna Chris , Reed Michael , Toth Jennifer , Lipton Allan , Ali Suhail M. 
Published: March 2020

7055 Background: The Lung Cancer Screening Trial has shown an overall survival (OS) benefit and reduced lung cancer mortality in the 55-74 age group (gp). We chose to evaluate whether NSCLC patients aged 75-84 are increasing in the USA and whether they would benefit from aggressive therapy. Methods: SEER-17 was used to calculate NSCLC rates during the years 2000-2008. SEER-9 was used to estimate the proportional change in both 55-74 and 75-84 gp from 1973-2008. OS was analyzed in a modern population from SEER-17 (2004-2008) to assess the effects of increasingly aggressive therapy (observation(Ob), radiation (RT) or lobectomy (LB)) for a proposed screening population with T1N0 tumors. Chi-square test and Cox Regression (CR) were used to evaluate OS. Paired T-tests assessed changes in rates and proportions over time. Results: The 55-74 gp rose from 64.4% in 1973 to 67.25% in 1984, but fell to 58.8% by 2008, while the 75-84 gp rose from 12.1% in 1973 to 24% in 2008 (p<0.01), similar in both sexes. The rates/100,000 have been increasing in the 75-84 gp (p=0.02), mainly in females (p=0.003) while the rates in the 55-74 gp did not vary, but fell for men (p=0.03). In the Ob gp (n=1344), NSCLC was the most common cause of death (COD) in the 55-74 (29.8%) and 75-84 gp (40.6%), more than all other CODs combined (median survival (MS) = 11mn). CR revealed that OS was associated with the 55-74 gp (0.59) and females (0.62) (p < 0.001). In the RT gp (n=1870), MS was 14mn and lung cancer was the most common COD at 27.7% (55-74) and 28.8% (75-84), again more than all other CODs combined. CR found that females (0.68) and black race (0.72) had better OS (p<0.017), but age was not. MS was 24 mn in the LB group (n=9384). COD from NSCLC and all other CODs was 8.2% and 6.1% (55-74) and 10.9% and 11.4% (75-84). CR showed that 55-74 (0.36), females (0.58), and Asians (0.73) had lower death rates (all p<0.015). Mean OS between the 55-74 (26.0) and 75-84 (24.2) gp showed a small yet significant difference. Conclusions: Rates and proportions of NSCLC have been steadily increasing in the 75-84 gp. These data show that COD by lung cancer decreased significantly with increasingly aggressive treatment and treatment reduced the effects of age gp on survival. We feel that screening may be of benefit to the 75-84 gp.