bluuebunny/crossref_metadata_2025_split huggingface dataset:
A feasibility study of induction pemetrexed plus cisplatin followed by extrapleural pneumonectomy (EPP) and postoperative hemithoracic radiation (H-RT) for malignant pleural mesothelioma (MPM): First all-Japan trial.
Authors: Tanaka Fumihiro , Hasegawa Seiki , Okada Morihito , Yamanaka Takeharu , Soejima Toshinori , Kamikonya Norihiko , Fukuoka Kazuya , Yokoi Kohei , Nakano Takashi 
Published: March 2020

7583 Background: The first all Japan multi-institutional trial was conducted to evaluate the feasibility of tri-modality therapy for MPM with support by the Special Coordination Funds for Promoting Science and Technology from the Japanese Ministry of Education, Culture, Sports, Science and Technology, and the first analyses data including macroscopic complete resection (MCR) rate by EPP as well as treatment-related mortality were presented at the ESMO meeting 2011 after completion of planned patient enrollment, and all survival data collection has been completed in January 2013. Methods: Major eligibility criteria: a histologically confirmed diagnosis of MPM, including all subtypes clinical T0–3, N0–2, M0 disease considered to be completely resectable; no prior treatment for the disease; age between 20 and 75 years; ECOG performance status of 0 or 1; a predicted postoperative forced expiratory volume in 1 s of >1000 ml; and written informed consent. Treatment methods: Induction chemotherapy of pemetrexed 500 mg/m2 plus cisplatin 60 mg/m2 for 3 cycles, followed by EPP and postoperative H-RT (54 Gy). Primary endpoints: MCR rate by EPP and treatment-related mortality for tri-modality therapy. Results: A total of 17 institutions in Japan with certified specialists in oncology, surgery and radiation therapy participated in this trial. The study was initiated in May 2008 and patient enrollment was completed in November 2010 with 42 eligible patients. Median age 64.5 (range 43–74), M: F = 39:3, Clinical stage I:II:III = 14:13:15, Histological type epithelial: sarcomatous; biphasic; others = 28: 1: 9: 4. The trial met the primary endpoints with MCR rate of 71% and treatment-related mortality of 9.5%. All survival data to calculate disease-free survival and overall survival at 2 years after EPP have been collected, and results will be presented at the meeting. Conclusions: Results of the present trial will be the foundation of treatment strategy for resectable MPM. Clinical trial information: 000001154.
A clinical-based risk score for decision making for surgery after induction chemotherapy in malignant pleural mesothelioma patients.
Authors: Opitz Isabelle , Friess Martina , Stahel Rolf A. , Weder Walter 
Published: March 2020

7587 Background: Scoring tools predicting the potential benefit from surgery after induction chemotherapy in mesothelioma patients may influence decision making. Our score is based on 4 clinical variables available before surgery. Methods: 128 patients were uniformly treated with cisplatin based induction chemotherapy followed by extrapleural pneumonectomy between 1999 and 2011. Based on clinical experience and survival influencing factors resulting from uni-and multivariate analysis, we designed a risk score. All 4 variables building up the score were available for 59 patients: pre chemotherapy volumetry above 500 ml, non-epithelioid histotype in the diagnostic biopsy, pre chemotherapy CRP value above 30 mg/l and progressive disease after chemotherapy according to modified RECIST criteria. The 5 resulting groups were analyzed for overall survival (OAS) and progression free survival (PFS) using Kaplan-Meier and Cox regression model. Results: The score strongly stratified patients into high and low risk groups for shorter OAS (Table) (p<0.0005). As to PFS, patients with Score 0 also had significantly longer median PFS (16 months; 95% CI: 12; 20) in comparison to patients with score 3 or higher (6 months; 95% CI: -; -) (p<0.0005). In Cox regression analysis the risk factor for shorter OAS and PFS increased correspondingly to our score. Conclusions: Our new score based on 4 clinical variables available before surgery identifies patients’ subgroups who may benefit from surgery after induction chemotherapy, which will be further assessed prospectively. [Table: see text]
Phase I/IIa study of the novel combination of bendamustine (B) with irinotecan (I) followed by etoposide (E) and carboplatin (C) in untreated patients (Pts) with extensive-stage small cell lung cancer (ESSCLC).
Authors: Allendorf Daniel Joseph , Bordani Rodolfo , Grant Stefan C. , Saleh Mansoor N. , Jerome Mary , Miley Debi , Cantor Alan , Reddy Vishnu , Robert Francisco 
Published: March 2020

7591 Background: Standard therapy for ESSCLC consisting of E and a platin drug (Plat) yields a median time to progression (TTP) of 4 months (m) and overall survival (OS) of 9 m. DNA damage from B is repaired by excision repair, akin to Plat. The activity of I, a topoisomerase (Top)-1 inhibitor, leads to increases in Top-2, the target of E. The sequence B+I → E+C was hypothesized to increase TTP by exploiting mitotic catastrophe. Methods: This is an open label trial enrolling pts with ESSCLC and evaluable disease. The phase I primary endpoint was to determine the maximum tolerated dose (MTD) of B+I; the phase IIa primary endpoint was TTP after B+I→E+C. Secondary endpoints were objective response rate (ORR) and OS. In the phase I (N=15), cohorts received I (150 mg/m2, d 1) with B at 80, 100, or 120 mg/m2/day (d 1,2) every 3 weeks for 3 cycles. Phase IIa Pts were treated at the recommended dose of B+I for 3 cycles followed by E (100 mg/m2, d 1-3) + C (AUC 6, d 1) for 3 cycles. Restaging was performed after 3 cycles of each regimen. The phase IIa was powered to detect a 30% increase in TTP from 4 to 5.2 m with a of 0.1. The Kaplan-Meier method was used to calculate TTP and OS. Toxicities were evaluated using the NCI CTCAE. Results: The MTD of B was not reached. The recommended phase IIa dose of B was 100 mg/m2; dose-escalation was allowed in subsequent cycles of therapy. Dose limiting toxicities were diarrhea, nausea, and vomiting. One treatment-related death from metabolic encephalopathy occurred in the phase IIa. The commonest grade 3/4 hematologic toxicity was neutropenia. Fatigue, nausea, vomiting, and diarrhea were common non-hematologic toxicities. Conclusions: B+I is an active regimen in ESSCLC and the treatment sequence B+I→E+C seems to improve the TTP and OS in ESSCLC compared to historic values for E+C. Toxicities were increased compared to historic values for E+C, but were manageable. Correlative studies with pre-treatment assessment of tumor ERCC-1, Top-1, and Top-2 as predictors of response are ongoing. Clinical trial information: NCT00856830. [Table: see text]
Small cell lung cancer (SCLC) among patients who are never smokers.
Authors: Varghese Anna M. , Yu Helena Alexandra , Won Helen H. , Sima Camelia S. , Riely Gregory J. , Krug Lee M. , Rekhtman Natasha , Kris Mark G. , Berger Michael F. , Zakowski Maureen Frances , Pietanza Maria Catherine 
Published: March 2020

7593 Background: Although most patients (pts) with SCLC are current or former smokers, SCLC has been reported in pts who are never smokers, most recently in pts with EGFR-mutant lung cancers who develop acquired resistance (AR) to EGFR tyrosine kinase inhibitors (TKIs). We describe clinical, pathologic, and molecular characteristics of never-smoking pts with SCLC at diagnosis and in the AR setting. Methods: We identified cases through systematic review of pts seen at MSKCC from 2005 – 2012. Smoking history was obtained prospectively. SCLC diagnosis was confirmed by expert pathology review. We collected age, sex, stage, treatment, and survival data. EGFR, KRAS, PIK3CA, and ALK testing and next generation sequencing of 279 cancer genes was performed on available samples. Results: 2.2% (23/1040, 95% CI 1.5 to 3.3%) of pts with SCLC seen at MSKCC were never smokers: 61% women, median 64 years, 74% extensive stage, and 22% with brain metastases at diagnosis. 83% (19/23) had de novo SCLC, whereas only 17% had SCLC as AR to EGFR TKI after treatment for EGFR-mutant lung cancers, all of whom had persistent EGFR mutation confirmed at resistance. Median survival from SCLC diagnosis is 23 months (95%CI: 11-26) for all pts and 23 months (95% CI: 8–27) for the 19 pts with de novo SCLC. Pathologic review demonstrated 19 cases of pure SCLC and 4 mixed histology cases with SCLC and other histologies. Treatment history was available for 15/19 pts with de novo SCLC: 53% etoposide-platinum sensitive. ALK rearrangement and KRAS mutations were identified in 0/5 and 0/10, respectively. One pt with de novo mixed SCLC and adenocarcinoma had an EGFR mutation and another pt with de novo pure SCLC had EGFR and PIK3CA mutations. Mutations were identified in p53 and Rb1 with amplification in TERT in 1 sample to date tested with next generation sequencing. Conclusions: 2% of pts with SCLC are never smokers. While transformation to SCLC can occur in the setting of AR to EGFR TKI, de novo SCLC occurs in the majority of our never smokers with this disease. EGFR mutations uniformly exist in SCLC in the AR setting. EGFR mutations were rare, and we found no KRAS mutations or ALK rearrangements. Comprehensive, multiplexed genotyping can aid in providing optimal care and facilitate research in this unique population.
Can hippocampus be spared in patients with small cell lung carcinoma (SCLC) during cranial radiation therapy (CRT)?
Authors: Kundapur Vijayananda , Ellchuk Tasha , Ahmed Shahid 
Published: March 2020

7596 Background: Although CRT is a standard therapy for prevention and treatment of brain metastases (BM) in patients with SCLC, neurocognitive impairment (NI) following therapeutic whole brain radiation treatment (WBRT) or prophylactic cranial irradiation (PCI) is a major problem and can cause impairment in quality of life. A RTOG study is assessing various outcomes by avoiding the hippocampus (AH) during WBRT in different malignancies. The estimated risk of hippocampal avoidance region metastases (HM) in patients with SCLC before & after WBRT/PCI is not known. AH during CRT may delay the onset of NI in such patients. Our study aims to determine risk of HM in patients with SCLC and to assess clinical factors correlate with it. Methods: A patients cohort of SCLC diagnosed and treated at the Saskatoon Cancer Center between 2005 and 2012 were followed. All MRI and/or CT scans were independently reviewed by a neuroradiologist. HM was defined as BM within 5 mm of hippocampus. Binary Logistic regression analysis was done to assess correlation between various clinical variables and HM using SPSS. Results: 162 patients with SCLC were identified, 60 (37%) have developed BM. The preliminary data of 39/60 patients is presented here. All 39 patients received CRT and 17 patients received upfront chemotherapy. Their median age was 63 yrs (range: 41-82) & M:F was 22:17. 30 (77%) had extensive stage SCLC and 30 (77%) had de novo BM before CRT. A total 198 (range: 1-33) BM were identified among these patients with a mean BM of 6.6 per patient. 4 (13.3%) of 30 patients had HM involvement with mean BM of 1.3 per patient. Median follow up was 13.5 months (range: 1-69). Post-CRT 13 (33%) of 39 patients (4 PCI, 9 WBRT) developed central nervous system (CNS) progression. None of 13 patients with CNS failure following CRT developed HM. Overall 4 (10.2%) of 39 patients developed HM. No clinical factors significantly correlated with HM. Conclusions: The preliminary result revealed that overall incidence of HM before and after WBRT/PCI is low. AH in such patients may consider during CRT to avoid NI. The study is ongoing and final analysis will be presented.
Development of a SOMAmer (slow off-rate modified aptamer)-based assay to detect NSCLC.
Authors: Park Noh Jin , Root Dana , Wang Xiuqiang , Diaz Angelica , Esmailpour Taraneh , Birse Charlies e , Lagier Robert , Sun Weimin , Morrone Robert J. , Waldman Frederic , Strom Charles m 
Published: March 2020

7601 Background: Support for low-dose helical computed tomography (CT) screening for lung cancer in a high risk population has emerged from the National Lung Screening Trial (NLST). However, the low specificity of CT raises concerns regarding the cost and potential morbidity associated with resection of benign nodules. Non-invasive lung cancer biomarkers may serve as a useful complement to imaging, providing a simple means to further clarify the diagnosis of suspicious pulmonary nodules. SOMAmer-based chip technology was previously used to identify a panel of serological biomarkers capable of accurately classifying NSCLC. Here we assess the analytical and clinical performance of an automated assay that uses SOMAmer reagents and qPCR to simultaneously quantify a subset of these markers (n=12). Methods: Biomarker levels were measured in sera from 43 subjects with stage I-III NSCLC and 63 long-term smoker controls. qPCR results were analyzed by relative (ΔΔCT) quantitation, which uses calibrator serum and a set of normalizers. Linear mixed-effects models were fit to identify key sources of analytical variability (variance components), including plate-to-plate, within-sample, and between sample effects. Clinical performance for distinguishing NSCLC from control sera was established by a random forest predictive model. Results: Median within-sample %CV for the 12 markers was 6.7%. Variance components analyses suggest that, on average, 5.7% of the variance for a given biomarker was due to within-sample effects, 5.2% to plate-to-plate effects, and 86.2% to between-sample effects. A 10-marker random forest model exhibited an AUC [95% CI] of 0.915 [0.905, 0.924], classifying NSCLC from control sera with 79% sensitivity and 90% specificity. Conclusions: We have developed a highly reproducible automated assay designed for the clinical laboratory. Combining SOMAmer-based protein capture and qPCR-based quantification, the assay monitors the levels of 12 potential lung cancer markers. An algorithm-based model incorporating 10 of these markers showed good accuracy for distinguishing NSCLC from control sera. Further studies are warranted to evaluate the performance of the test in classifying pulmonary nodules.
Randomized phase III trial of erlotinib (E) versus docetaxel (D) as second- or third-line therapy in patients with advanced non-small cell lung cancer (NSCLC) who have wild-type or mutant epidermal growth factor receptor (EGFR): Docetaxel and Erlotinib Lung Cancer Trial (DELTA).
Authors: Okano Yoshio , Ando Masahiko , Asami Kazuhiro , Fukuda Masaaki , Nakagawa Hideyuki , Ibata Hidenori , Kozuki Toshiyuki , Endo Tateo , Tamura Atsuhisa , Kamimura Mitsuhiro , Sakamoto Kazuhiro , Yoshimi Michihiro , Soejima Yoshifumi , Tomizawa Yoshio , Isa Shunichi , Takada Minoru , Saka Hideo , Kubo Akihito , Kawaguchi Tomoya 
Published: March 2020

8006 Background: E and D are standard cares for previously treated patients with advanced NSCLC. Although E shows significant clinical benefits over best supportive care in the EGFR wild type tumors, it remains unknown whether E or D is more active against the disease. Methods: This is an open-label, multi-center phase III study, sponsored by the Japanese National Hospital Organization. Patients were randomized to E (150 mg, daily), or D (60 mg/m2, q3w) by the minimization method according to gender, performance status, histology, and institution. The primary endpoint was progression free survival (PFS), and secondary endpoints included overall survival (OS), response rate, safety, and analyses on EGFR wild type tumors. Eligible patients were those with pathologically proven NSCLC with stage IIIB or IV (AJCC version 6) previously treated with one or two chemotherapy regimens including at least one platinum agent, evaluable or measurable disease, and ECOG PS 0-2. Target sample size was calculated to be 280 based on the assumption that E was superior to D in PFS (3.5 months [m] v 2.5 m, α =0.05 [two sided], β =0.80). Results: From August 2009 to July 2012, 301 patients were accrued from 41 institutions. In the ITT population, 150 and 151 patients were randomly assigned to E and D, respectively, including respective 109 (73%, E) and 89 (59%, D) with EGFR wild type tumors. Median PFS and OS for E v D were 2.0 m (95% CI: 1.3-2.8) v 3.2 m (2.8-4.0, log-rank p=0.092; HR=1.22, 95% CI: 0.97-1.55), and 14.8 m (9.0-19.4) v 12.2 m (9.0-15.5, p=0.527; HR=0.91, 95% CI: 0.68-1.22), respectively. In the EGFR wild type tumors, PFS and OS for E v D were 1.3 m v 2.9 m (p=0.013; HR =1.44, 95% CI: 1.08-1.92), and 9.0 m v 9.2 m (p=0.914; HR =0.98, 95% CI: 0.69-1.39), respectively. Main grade 3/4 toxicities were rash (13.3% [E] v 0.7% [D]) and leukopenia (5.4% [E] v 62.9% [D]). Conclusions: E failed to show better PFS over D. While PFS was significantly longer in D than E in EGFR wild type tumors, the difference did not translate into OS in this pragmatic trial. Clinical trial information: 000002314.
Effect of maintenance bevacizumab (Bev) plus pemetrexed (Pem) after first-line cisplatin/Pem/Bev in advanced nonsquamous non-small cell lung cancer (nsNSCLC) on overall survival (OS) of patients (pts) on the AVAPERL (MO22089) phase III randomized trial.
Authors: Rittmeyer Achim , Scherpereel Arnaud , Gorbunova Vera A. , Gervais Radj , Vikström Anders , Chouaid Christos , Chella Antonio , Kim Joo-Hang , Ahn Myung-Ju , Reck Martin , Pazzola Antonio , Kim Heung Tae , Aerts Joachim , Groen Harry J.M. , Morando Claire , Loundou Anderson , Barlesi Fabrice 
Published: March 2020

8014 Background: Maintenance monotherapy has been associated with improved survival for NSCLC pts. AVAPERL was designed to evaluate the safety and efficacy of bevacizumab with or without pemetrexed as continuation maintenance treatment and demonstrated improved progression-free survival (PFS) (Barlesi, JCO in press). Methods: Pts with advanced nsNSCLC received first-line Bev (7.5 mg/kg), cisplatin (75 mg/m2), and Pem (500 mg/m2) every 3 weeks (q3w) for 4 cycles. Those non progressing were randomized to maintenance Bev (7.5 mg/kg) +/-Pem (500 mg/m2) q3w until progressive disease or unacceptable toxicity. The primary end point (PFS) was met. An independent update analysis has been conducted to assess OS. Results: A total of 376 pts receive induction treatment; 125 and 128 were randomized to the Bev-alone and Bev+Pem arms, respectively. Induction therapy resulted in confirmed disease control in 71.9% of pts. After a median follow-up of 14.8 months, PFS for the Bev+Pem arm was significantly improved both from induction (10.2 v 6.6 m, HR 0.58 [0.45-0.76], p<.0001) and randomization (7.4 v 3.7 m, HR 0.57 [0.44-0.75], p<.0001). With 58% of events, OS for the Bev+Pem arm was also improved both from induction (19.8 v 15.9 m, HR 0.88 [0.64-1.22], p=.32) and randomization (17.1 v 13.2 m, HR 0.87 [0.63-1.21], p=.29). The PFS and OS improvements were comparable across age, PS, smoking status, and response to induction (SD vPR/CR) subgroups. No new safety signal was observed during this updated analysis. Conclusions: Continuation maintenance with Bev+Pem in an unselected population of nsNSCLC pts who had achieved disease control after induction was associated with an increase by almost 4 months in OS benefit over standard Bev alone. Clinical trial information: NCT00961415.
LUX-Lung 6: A randomized, open-label, phase III study of afatinib (A) versus gemcitabine/cisplatin (GC) as first-line treatment for Asian patients (pts) with EGFR mutation-positive (EGFR M+) advanced adenocarcinoma of the lung.
Authors: Wu Yi Long , Zhou Caicun , Hu Cheng-Ping , Feng Ji Feng , Lu Shun , Huang Yunchao , Li Wei , Hou Mei , Shi Jian Hua , Lee Kye Young , Massey Dan , Shi Yang , Chen Jiongjie , Zazulina Victoria , Geater Sarayut Lucien 
Published: March 2020

8016 Background: A is an oral, irreversible, ErbB Family Blocker, blocking signaling from EGFR (ErbB1), HER2 (ErbB2) and ErbB4. A was superior to first-line pemetrexed/cisplatin in a global phase III trial (LUX-Lung 3) in EGFR M+ NSCLC. This study compared the safety and efficacy of first-line A with GC in EGFR M+ Asian pts. Methods: The trial was conducted in Asian countries. Following central testing for EGFR mutations (TheraScreen EGFR RGQ PCR kit), 364 pts (stage IIIB/IV, PS 0–1, chemo-naïve) were randomized 2:1 (A: 242; GC: 122) to daily A 40 mg or IV GC (1,000 mg/m2 D1, 8 + 75 mg/m2q21 days up to 6 cycles). Primary endpoint was PFS by central independent review. Results: Baseline characteristics were balanced in both arms: Female (64.0 vs 68.0%), non-smoker (74.8 vs 81.1%), exon 19 deletion (51.2 vs 50.8%), L858R (38.0 vs 37.7%) in A and GC arms, respectively. PFS was significantly prolonged with A compared with GC by independent review (median PFS 11.0 vs 5.6 months, HR=0.28, p<0.0001); this finding was consistent across all subgroups. Results from the investigator review were similar: HR=0.26, p<0.0001, median 13.7 (A) vs 5.6 months (GC). Objective response (66.9% vs 23.0%, p<0.0001) and disease control (92.6% vs 76.2%, p<0.0001) rates (ORR/DCR) were significantly higher with A. OS, based on 43% of events shows HR=0.95, p=0.7593. Drug-related AEs of ≥G3 were reported in 36.0% (A) and 60.2% (GC) of pts, the most common of which were rash/acne (14.6%), diarrhea (5.4%) and stomatitis/mucositis (5.4%) with A and neutropenia (17.7%), vomiting (15.9%) and leukopenia (13.3%) with GC. Related AEs led to discontinuation in 5.9% (A) and 39.8% (GC) of pts. Patient reported-outcomes (PROs) showed significantly better control of cancer-related dyspnea, cough and pain with A. Conclusions: In EGFR M+ Asian pts, A significantly prolonged PFS with significant improvements in ORR, DCR, PROs. AEs in both arms were as expected, with a more favorable safety profile with A. LUX-Lung 6 is the largest prospective trial in EGFR M+ lung cancer, providing further evidence of superiority of A over standard chemotherapy in this setting. Clinical trial information: NCT01121393.
Explicit and implicit attitudes toward lung cancer (LC) relative to breast cancer (BC).
Authors: Schiller Joan H. , Bowden Chris J. , Mills Jennifer , Lang Edward , Dickson Holli , Hamann Heidi A , Sriram N. 
Published: March 2020

8017 Background: Emerging research suggests that LC may be associated with greater levels of stigma, shame and hopelessness compared to other cancers. This study measured explicit, conscious attitudes (EAs) and used the Implicit Association Test (IAT) to assess implicit, unconscious attitudes (IAs) of LC relative to BC. Methods: To assess EAs, participants (Ps), [people with cancer (n=243), caregivers (n=677), healthcare providers (HCPs, n=142), and the general public (n=864)] were asked to rate their agreement, on a six-point scale, with statements about how people with LC and BC “do feel” (descriptive attitudes) or “ought to feel” (normative attitudes) about their disease. IAs were measured with three IATs that used LC or BC images with words representing good/bad; hope/despair; or suitable/shameful. An IAT D score indicated the strength of bias against LC relative to BC: >0.65 = strong bias; 0.35-0.65 = moderate bias; 0.15-0.35 = slight bias; -0.15 -+0.15 = no bias, and < -0.15 indicated bias against BC. Results: EAs and IAs were substantially more negative towards LC. Most Ps provided more negative ratings for LC than BC for both descriptive (70%vs.8%) and normative statements (56% vs. 3%). Ps had strong negative IAs towards LC compared to BC (bad: 74% vs. 10%; despair: 75% vs. 9%; shame: 67% vs. 17%). These trends were consistent across caregivers, patients, HCPs, and the public. EAs and IAs were uncorrelated. Conclusions: Ps had greater explicit and implicit negative bias against LC compared to BC. [Table: see text]