bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comorbidity and survival for patients with advanced-stage non-small cell lung cancer.
Authors: Chrischilles Elizabeth A. , Abu Hejleh Taher , Carter Knute D. , Pendergast Jane F , Halfdanarson Thorvardur Ragnar , Fletcher Robert H. , Wallace Robert B 
Published: March 2020

e19065 Background: Treatment decisions for patients with advanced stage (stages IIIB and IV) non-small cell lung cancer (AS NSCLC) are influenced by comorbidity at time of diagnosis. We studied the effects of comorbidity on survival and whether effects differ for short-term (120 days) vs. for long-term (>120 days) survival. Methods: Data were from surveys and medical records of 1498 patients withnewly diagnosed AS NSCLC in the Cancer Care Outcomes Research and Surveillance Consortium (CanCORS). Respiratory disease severity and comorbidities at diagnosis were measured from the Adult Comorbidity Evaluation (ACE-27) index and model fitting used the Akaike Information Criteria. The log-rank test was used for univariable survival models, and Cox proportional hazards regression for multivariable survival models. Results: Five comorbidities were significantly associated with survival and 437 (29.2%) patients had one or more of these. Survival to 120 days was significantly poorer for patients with a baseline diagnosis of stroke [hazard ratio (HR) 1.92; 95% confidence interval (CI) 1.26–2.93], diabetes (HR 1.33, 95% CI 1.08–1.65), or congestive heart failure (HR 1.45, 95% CI 1.07–1.96), controlling for age, gender, smoking status, stage, severe respiratory disease, and brain metastases. Given survival to 120 days (885 pts, 59%), survival beyond that was significantly poorer only for patients with baseline arrhythmia (HR 1.47, 95% CI 1.15–1.87) or end stage renal disease (HR 1.82, 95% CI 1.09–3.04), controlling for the covariates above. Adjustment for chemotherapy use had no effect on these associations. Conclusions: Several comorbidities present at diagnosis affected survival for AS NSCLC, with some comorbidities having a more immediate relationship to survival than others. Our finding provides information that could be used to tailor treatment decisions to patients’ comorbidities at diagnosis.
Icotinib and whole brain radiotherapy (WBRT) for patients with brain metastases from non-small cell lung cancer (NSCLC): Preliminary results of a phase II study.
Authors: Yun Fan , Huang Zhiyu , Gong Lei , Yu Haifeng , Yang Haiyan , Lu Maio lu , Mao Weimin 
Published: March 2020

e19073 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, have shown efficacy in advanced NSCLC with brain metastases (BM). Icotinib is a new EGFR-TKI. A randomized, double blind phase III trial proved that icotinib was non-inferior to gefitinib in advanced NSCLC. We have conducted a phase II study to evaluate the efficacy and safety of icotinib in combination with WBRT in Chinese NSCLC patients with BM. Methods: From January 2012 to January 2013, 20 patients aged 18-75 years with ECOG PS 0-2 and BM from NSCLC,were recruited regardless of EGFR status. The treatment comprised icotinib 125mg, TID concurrently with WBRT (30Gy/10f/2w). CSF and plasma samples were collected at the same time from 10 patients at least 5 days after icotinib treatment. The concentrations of icotinib in the CSF and plasma were measured by high performance liquid chromatography coupled with tandem mass spectrometry. The primary end point was progression-free survival (PFS) . Additional end points were response rate, safety and CSF concentrations of icotinib. Results: The median PFS was 7.3 months [95% confidence interval (CI) 4. 2-9.8]. Patients with EGFR mutation-positive disease had significantly longer median PFS versus EGFR wild-type disease [NR versus 4.2 months (95% CI 2.9-5.1); P = 0.000]. The CNS response rates were 25% complete response (n=5), 55% partial response (n= 11), 15% stable disease (n=3), and 5% progressive disease (n =1). The overall CNS response rate was 80% (n = 16). The most common adverse events were rash (40.0%), diarrhea (15.0%),nausea (45.0%), vomiting (20.0%), headache (35.0%)and fatigue (45.0%). And no patient experienced grade ≥ 3 toxicity. The mean plasma and CSF concentrations of icotinib were 936.47 ± 503.80 and 8.93 ± 8.01 ng/ml, respectively, and the mean ratio of CSF-plasma concentration was 1.04% ± 0.95. Conclusions: Icotinib was well tolerated and showed promising activity in combination with WBRT in patients with BM from NSCLC. The concentrations of icotinib in CSF were low. Further randomized trials are warranted. Clinical trial information: NCT01514877.
CT image characteristics of anaplastic lymphoma kinase fusion gene positive (ALK-P) advanced stage non-small cell lung cancer (NSCLC).
Authors: Oyakawa Takuya , Takahashi Toshiaki , Imai Hisao , Akamatsu Hiroaki , Ono Akira , Taira Tetsuhiko , Kenmotsu Hirotsugu , Naito Tateaki , Murakami Haruyasu , Endo Masahiro , Yamamoto Nobuyuki 
Published: March 2020

e19074 Background: Although several clinical and pathological characteristics of ALK-P NSCLC have been reported, to our knowledge, only one report regarding CT findings of resected early stage ALK-P NSCLC have been published (Fukui T et al. Lung Cancer 2012). They concluded resected ALK-P tumors exhibited a solid pattern without ground glass opacities (GGO). However, there is no report regarding CT image characteristics of advanced stage ALK-P NSCLC. Methods: We retrospectively reviewed CT image findings of 20 patients with advanced ALK-P NSCLC and 32 patients with ALK-negative (ALK-N) NSCLC between November 2010 and January 2013 at Shizuoka Cancer Center in Japan. Primary lesion (PL) was classified into three types: GGO (Type G), focal GGO with solid central components (Type GS), solid nodules without GGO (Type S). Results: Characteristics of patients with ALK-P (N=20)/ ALK-N (N=32) were: 7 /17 males and 13/15 females, median age ;51/63 years, non-smokers 13/8 and smokers 7/24, adenocarcinoma;19/32, stage III; 2 /9, stage IV;18/23. None of PL of both ALK-P and ALK-N showed type G. PL of ALK-P (type GS/S;13/7) had a significant high frequency of type GS than that of ALK-N (type GS/S;8/24) (p=0.004). Lymph node metastases were observed in 16 of 20 ALK-P cases, and 26 of 32 ALK-N. The frequency of fusions of metastatic lymph nodes in ALK-P cases (75%) was significantly higher than that in ALK-N cases (31%) (p=0.010). And the frequency of increased concentration of mediastinal fat tissues around metastatic lymph nodes in ALK-P cases (50%) was also significantly higher than that in ALK-N cases (12%) (p=0.011). Intrapulmonary metastases on the initial CT were observed more frequently in ALK-P (12 of 20 cases) than in ALK-N (6 of 32 cases) (p=0.013). There were no specific features regarding liver, bone and brain metastases in ALK-P cases. Conclusions: Advanced stage ALK-P NSCLC has several CT image characteristics. These findings may reflect biological features of ALK-P NSCLC, and can help clinicians suspect their NSCLC patients of having ALK rearrangement.
Study KBP-2010-CPHG: Characteristics and management of 968 new cases of small-cell lung cancer (SCLC).
Authors: Dayen Charles , Coëtmeur Daniel , Lecerf Celine , Diximier Adrien , Lemaire Bertrand , Martin Michel , Lafourcade Marie-Pierre , Fraboulet Gislaine , Leveiller Guillaume , Lecuyer Emmanuelle , Mathieu Jean-Pierre , Nocent-Ejnaini Cecilia , Dumont Patrick , Peureux Marc , Dehette Stephanie , Locher Chrystele , Le Treut Jacques , Debieuvre Didier , Martin Francis , Grivaux Michel 
Published: March 2020

e19078 Background: In recent years, many major advances have been made in non-small-cell lung cancer (NSCLC), and in particular in adenocarcinoma, but not in SCLC. In 2010, the French College of General Hospital Respiratory Physicians (CPHG) performed a prospective multicentre epidemiological study (KBP-2010-CPHG) to describe the baseline characteristics and management of all new cases of primary lung cancer and to evaluate survival. The present abstract reports results in SCLC patients. Methods: 7,051 patients ≥18 years presenting with a new case of primary lung cancer, histologically or cytologically diagnosed between 1 January and 31 December 2010 and managed in the respiratory department of one of the 104 general hospitals participating in the study, were included. A standardised form was completed for each patient. A steering committee checked data collection exhaustiveness. SCLC data were analysed separately. Results: There were 968 SCLC patients: mean age, 65.6 years (+/-10.6); 23.2% female; 4.4% non-smokers (11 % in women), 35.8% ex-smokers, 59.8% current smokers; 63.4% with performance status 0 or 1; 59.9% having lost weight within the previous 3 months (19.8% of whom had lost >10 kg). Main tumour characteristics at diagnosis were: 71.2% stage IV, 24.7% stage IIIA or IIIB, 4.1% of stage <III. 15.2% of patients received chemo-radiotherapy and 73.4% chemotherapy (86.2% platinum-based). Carboplatin was more commonly used in patients >70 (59.1%) than <70 years of age (40.9 %). One-year mortality was 64.2%. Compared with NSCLC patients, patients with SCLC more frequently were active smokers (59.8% vs.47.6%), lost weight (59.9% vs. 52.4%), and presented with stage IV tumour at diagnosis (71.2% vs. 58.3%); first line therapy was more frequently platinum-based chemotherapy (86.2% vs. 61.2%) and less frequently curative surgery (1.6% vs. 19%), and mortality was higher (64.2% vs. 55.2%). Conclusions: In 2010, prognosis remains poor in SCLC. Compared with NSCLC, it was more frequently associated with active smoking and stage IV disease, and showed a lower rate of surgery.
Natural history of malignant bone disease in non-small cell lung cancer: Preliminary results of a multicenter bone metastasis survey.
Authors: Santini Daniele , Intagliata Salvatore , Ibrahim Toni , Ferraù Francesco , Barni Sandro , Moscetti Luca I. , Mansueto Giovanni , Comito Francesca , Pantano Francesco , Longo Flavia , Russo Antonio , Satolli MAntonietta , Adamo Vincenzo , La Verde Nicla Maria , Badalamenti Giuseppe , Ottaviani Davide , Ferzi Antonella , Addeo Raffaele , Vasile Enrico , Tonini Giuseppe 
Published: March 2020

e19084 Background: Bone metastases represent an increasing clinical problem in advanced non-small cell lung cancer (NSCLC) as disease-related survival improves. This is a multicenter, retrospective survey aimed to explore the impact of bone involvement in this severe, life-threatening disease. Methods: Data on clinicopathology, skeletal outcomes, skeletal-related events (SREs), and bone-directed therapies for 421 deceased NSCLC patients (48.6% aged >66 years) with evidence of bone metastasis were statistically analyzed. Results: ECOG performance status at diagnosis of NSCLC was 0 in 41.4% of patients, 1 in 42.8% and 2 in 13.9%. The most frequent stage at diagnosis was IV (76.8%). Adenocarcinoma was the commonest histotype (70.3%) and EGFR status was unknown in 77.7%. Chemotherapy was the preferred I line treatment in 82.2%. Lung cancer frequently spreaded to bone, with metastases evident at diagnosis in up to 57.2% of patients. In the remaining cases median time to bone metastases was 9 months. Patients ECOG performance status when bone metastases were detected was 1 in 46.6% and 2 in 22.9%. In our sample multiple bone metastases were detected in 82.5% of patients and 71.2% were osteolitic. Axial skeleton was interested in 74.6% of cases, pelvic bones in 46.7% and limb bones in 29.3%. Bone metastases related pain was reported by 84% of patients. Median Verbal Numerical Rating Scale (VNRS) for pain was 4 and it measured >4 in 47.2% of cases. Bisphosphonates was administered in 65.6% of patients; zoledronic acid was mainly used (61.1%). Osteonecrosis of the jaw was reported in only 1.1 % of cases. Median number of SREs/patient was one, less than half of the patients (41.7%) experienced at least one SRE, 21.2% experienced at least two SREs, and only 2.1% experienced at least three SREs. The most common SRE was the need of radiotherapy (73.8%). Median time to first SRE was 3 months. Median survival after bone metastases diagnosis was 8 months and after first SRE was 6 months. Conclusions: These preliminary data suggest that bone metastases are a relevant clinical event in the natural history of patients affected by NSCLC. Final results will be available next ASCO meeting.
Racial disparities and survival with non-small lung cancer (NSCLC) at an urban safety net hospital.
Authors: Ernst David J. 
Published: March 2020

e19102 Background: Disparities in cancer outcomes have been documented for many tumor types. This study aims to investigate the influence of race on clinical presentation, treatment and outcome of non-small cell lung cancer at a safety net hospital. Methods: A retrospective review of all patients with NSCLC diagnosed at an urban safety net hospital was done. Demographic data, diagnostic approach, primary therapy, and survival were analyzed. Results: There were 359 patients with NSCLC who met study inclusion criteria. There were 179 Caucasian, 177 African American, and 3 Asian patients. Nearly half of all patients had metastatic disease at the time of diagnosis (Stage I 15%, Stage II 5%, Stage III 28%, and Stage IV 49%). Treatment varied by disease stage, but not by race, 35.2% Caucasians and 39.5% African Americans were treated with radiation, 42.5% Caucasians and 44.6% African Americans were treated with chemotherapy, and 26.3% Caucasians and 20.9% African Americans were treated with surgery. Median survival was very short and again, did not vary by race: for Caucasians diagnosed with any stage of NSCLC was 6.439 months, whereas in African Americans it was 7.852 months. Conclusions: In a safety net hospital setting, there were no disparities in treatment based on race and median survival in this study was uniformly poor. Significant comorbidity was likely and will be investigated further.
Role of IGF-1/IGFBP3 in non-small cell lung cancer sensitivity to therapy.
Authors: Ibañez de Cáceres Inmaculada , Holgado Esther , Pernia Olga , De Castro Javier , Hitt Ricardo , Conde Esther , López-Ríos Fernando , Cortes Semperes Maria , Perona Rosario , Belda-Iniesta Cristobal 
Published: March 2020

e19123 Background: Molecular mechanisms of drug-resistance remain still unclear; it is believed multifactorial, involving host factors, numerous molecular events as well as genetic and epigenetic changes. We were aimed to use massive expression assays before and after epigenetic treatment to explore predictors for platinum and radiation therapy in NSCLC. Methods: By using an expression microarray analysis, we looked for those genes reactivated in a set of two cisplatin (CDDP) resistant and sensitive NSCLC cell lines after epigenetic treatment. Gene expression, promoter methylation and CDDP-chemoresponse were further analyzed in three matched sets of sensitive/resistant cell lines, 23 human cancer cell lines and 36 NSCLC specimens. Then, to investigate the importance of methylation in radiosensitivity, we have developed radiation clonogenic cell survival assays with three paired Sensitive/CDDP-Resistant cell lines that present a different gene expression and promoter methylation profile. Finally, we have explored in vitro data into three cohorts of patients from different institutions that were treated with radio, chemoradiation or chemotherapy alone. Results: IGF-1/IGFBP3 axis was significantly associated with response to therapy and promoter methylation of IGFBP3 was critical to predict biological behavior. In this regard, hypermethylated and semimethylated cell lines presented a higher sensitivity to radiotherapy and cisplatin than cell lines completely unmethylated for IGFBP3 promoter. However, when resistance to cisplatin treatment was not mediated by IGFBP3 promoter methylation there were also not significant changes regarding sensitivity to radiotherapy treatment. Finally, in vitro data for IGF-1/IGFBP3 axis were confirmed in three cohorts of patients. Conclusions: IGF-1/IGFBP3 axis plays a central role in resistance to chemo- and radiation therapy in NSCLC patients.
Quantitative identification of mutant alleles derived from lung cancer in plasma cell-free DNA via anomaly detection using deep sequencing data.
Authors: Uchida Junji , Kukita Yoji , Taniguchi Kazuya , Oba Shigeyuki , Nishino Kazumi , Kumagai Toru , Okuyama Takako , Niki Toshie , Imamura Fumio , Kato Kikuya 
Published: March 2020

e19153 Background: Selection of lung cancer patients to be treated with EGFR-TKI (gefitinib and erlotinib) is currently based on the presence of activating mutations in the EGFR kinase domain. The diagnosis of the mutations is based on biopsy samples; the procedure is invasive, and often difficult to perform. A non-invasive diagnostic procedure is desirable. Methods: We established a non-invasive diagnostic system to detect somatic mutations including three activating mutations (exon 19 deletion, L858R, L861Q) and one resistant mutation (T790M) with single-pass deep sequencing of EGFR gene fragments amplified from patients’ plasma DNA using Ion Torrent PGM. In principle, substitutions or deletions significantly higher (p=0.00002) than the error rates determined with the normal samples were judged as mutations. Read errors of the system were determined with deep sequencing (>100,000 reads) of EGFR fragments. The detection limits were less than 0.01% for the exon 19 deletion and L858R, 0.01% for L861Q, and 0.05% for T790M. Results: We examined 155 samples, mostly plasma cell-free DNA, with mutation data of primary lesions. Exon 19 deletion, L858R, and L861Q were detected in 44 out of 72 samples (61.1%), 32 out of 56 (57.1%), and four out six, respectively. T790M was found in 26 samples, five of which did not accompany activating mutations. Considerable numbers of samples were collected from the same patients at different time points in the disease course. A temporal analysis revealed rapid disappearance of mutations by the EGFR-TKI therapy before radiological changes. Conclusions: Deep sequencing of amplified EGFR fragments from plasma DNA could detect mutations in lung cancer tissues. Results of the temporal analysis suggested potential applications for disease management and for therapeutic decision making to select EGFR-TKI. Clinical trial information: UMIN000006762.
Predictive value of serum nitric oxide for bevacizumab response in patients with non-small cell lung cancer.
Authors: Suzuki Hiroyuki , Ohsugi Jun , Hasegawa Takeo , Yaginuma Hiroshi , Okabe Naoyuki , Muto Satoshi , Owada Yuki , Gotoh Mitsukazu 
Published: March 2020

e19162 Background: Bevacizumab (BEV), an inhibitory monoclonal antibody to VEGF, is widely used to treat patients with non-small cell lung cancer (NSCLC), but biomarkers that predict BEV response are controversial. Reportedly, hypertension is linked to response to BEV therapy, possibly because BEV might suppress vascular nitric oxide (NO) production. However, the usefulness of serum NO (NOs) as a predictive biomarker for BEV therapy has not previously been shown. Here, we studied the predictive value of NOsin BEV-treated patients with NSCLC. Methods: Fifteen patients with advanced or recurrent NSCLC treated with BEV-based regimens were evaluated retrospectively. Blood samples were taken before treatment (Pre), and after the 1st and 2nd chemotherapy courses (Post1 and Post2, respectively). NOs (NO2–/NO3–) was assayed by the Griess method. Relationships between clinical parameters (e.g., clinical responses, adverse events) were analyzed against NOs. This study was approved by the ethics committee of Fukushima Medical University. Results: Mean Pre NOs was 70.3 ±10.5 μmol/L (range: 7.7–138.6 μmol/L). Significant decreases were observed at Post1 (34.6 ± 6.4 μmol/L; P = 0.013) and Post2 (29.6 ± 7.6 μmol/L; P = 0.046) compared to Pre values. Post/Pre NO ratios correlated significantly with hypertension onset (Post1/Pre: P = 0.012; Post2/Pre: P = 0.001). Notably, Post/Pre NO ratios correlated with clinical treatment responses—significantly so for Post2/Pre (Post1/Pre: P = 0.06; Post2/Pre: P = 0.005). Conclusions: NOs, could be a predictive biomarker for response to BEV in patients with NSCLC. Prospective confirmation is needed; we are conducting a prospective translational study of NO in BEV therapy. [Table: see text]
A phase II pilot efficacy trial of the combination regimen peg asparaginase/peg liposomal doxorubicin/dexamethasone (ODD) in patients with refractory lymphoid malignancies (NCT00837200).
Authors: Drabick Joseph J. , Lapsiwala Ritu , Talamo Giampaolo , Epner Elliot E , Supko Jeffrey G. , Claxton David , Ehmann W. Christopher , Lander Mary , St. Pierre Michelle , Rybka Witold B. 
Published: March 2020

e19502 Background: Asparaginase is a mainstay of the treatment for ALL depriving the malignant cells of asparagine leading to cell death. There are reports of asparaginase activity in non-ALL malignancies including CLL, NHL, and multiple myeloma. We developed a combination regimen with full dose PEG-Asparagase (O) together with low dose liposomal doxorubin (D) and dexamethasone (D) (ODD regimen) as a non-myelotoxic regimen for pts with advanced lymphoid malignancies and impaired bone marrow function, hoping this novel approach of inducing asparaginine deficiency would translate into benefit. Methods: A phase II trial of ODD with the O given D1 and D15 at 2500 IU/m2, D given D1 and D15 as 20 mg/m2 and the Dex given as 20 mg D1, D8, D15 and D22 of a 28 day cycle was initiated. Pts with any non-ALL lymphoid malignancy were eligible if they had failed at least one prior standard regimen. The study had a Simon 2-stage design with Response Rate as the primary endpoint. Secondary endpoints were safety and correlation of asparginase levels with response/toxicity. Results: 13 pts enrolled of 16 screened of whom 12 were evaluable for response. These included 7 MM pts and 6 with diffuse large B-cell lymphoma. The pts were heavily pre-treated with 3 (range 1 to 8) median prior regimens. 6 of the13 pts were over 70 yrs. One pt progressed before one complete cycle was given so was not evaluable for response. 2 pts (both MM) had a response which was defined as Stable Disease > 2 months; the other 10 had Progressive Disease. One responding pt was later taken off for O-related toxicities (DVT/PE, elevated enzyme levels). Effective Asparaginase levels were obtained in the serum of most tested pts. In general, the regimen was well tolerated considering the advanced nature of these cases, but typical O related toxicities were observed. Conclusions: We conclude that the ODD regimen, although well tolerated, had little appreciable activity in this heavily pre-treated group of pts with refractory DLBCL and MM. Whether it would have meaningful activity in less advanced states of these diseases or other lymphoid neoplasms remains an open question. Clinical trial information: NCT00837200.