bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of delays in time to surgery for resectable stage IIIA non-small cell lung cancer with survival.
Authors: Combs Susan E , Tullio Katherine , Pennell Nathan A. 
Published: September 2018

e20056 Background: Delay in time to surgery (TTS) for early stage non-small cell lung cancer (NSCLC) may impact survival; however the effect of delayed TTS for patients with stage IIIA NSCLC is unclear. Methods: Patients with pathologic stage IIIA NSCLC who underwent curative intent resection with documented days from diagnosis to definitive surgery were identified in the National Cancer Database from 2004 to 2012. Patients with surgery on the day of diagnosis or more than 180 days after diagnosis, and those who received pre-operative systemic or radiation therapy were excluded. Association between TTS as a continuous variable by week and month was assessed by cox regression models. Multivariate cox proportional hazard models estimated the mortality risk associated with TTS as a continuous variable with age, sex, race, comorbidity score, pathologic T and N stage. Overall survival (OS) between immediate and delayed groups was estimated by Kaplan-Meier method and log-rank test. Results: Of patients with NSCLC who underwent definitive resection, 16,033 were confirmed to be pathologic stage IIIA. Median follow-up was 25 months, and 61% of patients died with a median survival of 32 months. Median time from diagnosis to surgery was 37 days. Five-year OS for patients with surgery in the first 37 days was 34.7%, compared to 30.1% in patients who had surgery after the first 37 days (p < 0.001). When grouped by increasing weeks of delay, the earliest significant survival difference was noted in patients resected within three weeks of diagnosis, with 5-yr OS of 35.2%, compared to 31.5% for patients treated more than three weeks later (p = 0.002). For each week of additional TTS, the associated risk of mortality increased by 1.2% (HR 1.012, 95% CI 1.007-1.016, p < 0.001) and 5.0% for each month of delay (HR 1.046, 95% CI 1.026-1.065, p < 0.001). In the multivariate model accounting for confounders, the mortality risk associated with delay to surgery increased by 0.75% with each additional week (HR 1.0075, 95% CI 1.003-1.012, p = 0.002). Conclusions: This analysis suggests that delays in time to curative intent resection for patients with stage IIIA NSCLC decreases the 5-year OS and thus the likelihood of cure.
Chemoradiotherapy (CRT) for locally-advanced (LA) lung cancer patients with interstitial lung abnormalities (ILA).
Authors: Kubo Toshio , Higo Hisao , Ninomiya Takashi , Ichihara Eiki , Ohashi Kadoaki , Sato Akiko , Hotta Katsuyuki , Tabata Masahiro , Makimoto Satoko , Ihara Hiroki , Masaoka Yoshihisa , Katsui Kuniaki , Kiura Katsuyuki 
Published: September 2018

e20057 Background: Interstitial lung disease (ILD) is an independent risk factor for lung cancer. The incidence of ILD in lung cancer patients is 5–10%. Although CRT is the standard treatment for LA lung cancer and has potential for long-term disease-free survival or cure, the treatment is avoided in patients with ILD because of the risk of severe radiation pneumonitis or acute ILD exacerbation. ILA has recently been evaluated using high-resolution computed tomography (HRCT) to assess interstitial changes. The aim of this study was to determine the feasibility and efficacy of CRT for LA lung cancer patients with ILA. Methods: Patients who underwent CRT for LA lung cancer at Okayama University Hospital between 2012 and 2015 were reviewed retrospectively. HRCT prior to treatment was evaluated by one pulmonologist and two radiologists using sequential reading. Results: Of 74 patients, ILA was present in 25 (33.8%) and indeterminate ILA was present in 23 (31.1%); 26 patients (35.1%) did not have ILA. Patient characteristics are shown below. Desaturation at rest (SpO2< 95%) and honeycombing on HRCT were not observed in patients with ILA. Only one patient with ILA had a low vital capacity (VC% of predicted, < 80%). Severe radiation pneumonitis (≥ grade 2) occurred in 32.0% of patients with ILA and 19.2% of patients without ILA (P=0.35). All radiation pneumonitis was controllable and grade 4 or 5 was not observed. Using multivariate analyses, treatment > 20 Gy involving > 25% of the lung volume was a predictive factor for severe radiation pneumonitis, but not ILA. The 2-year survival percentages of patients with and without ILA were 56.8% and 72.5%, respectively (hazard ratio, 1.21; 95% confidence interval, 0.76–1.90; P=0.42). Conclusions: Although severe radiation pneumonitis tended to increase, CRT was appropriate for patients with ILA without desaturation, low VC, and honeycombing on HRCT. [Table: see text]
Genomic and transcriptomic profiling of localized sarcomatoid carcinoma of the lung to reveal association between immune activation and a lower risk of recurrence.
Authors: Seth Sahil , Lee Won-Chul , Zhang Jianhua , Fujimoto Junya , Behrens Carmen , McDowell Christina , Kalhor Neda , Weissferdt Annikka , Papadimitrakopoulou Vassiliki , Heymach John , Gibbons Don Lynn , Futreal Andrew , Wistuba Ignacio Ivan , Amit Moran , Kadara Humam , Zhang Jianjun 
Published: September 2018

e20058 Background: The sarcomatoid carcinoma of the lung (SCL) is a rare subtype of non-small cell lung cancers (NSCLC). The prognosis of SCL is poor with 5-year survival of ~20%. There have been only a few studies on genomic landscape of SCL. Comprehensive genomic and transcriptomic profiles of SCL have not been systematically studied. Methods: In this study, we performed whole-exome sequencing and ultra-deep targeted sequencing of 400 cancer genes on 21 resected localized SCLs and matched normal lung tissues. RNA sequencing (RNA-seq) was also performed to 17 SCLs and matched normal lung tissues for those with materials available. Results: On average, 688 mutations including 503 non-synonymous mutations were identified per tumor. Canonical cancer gene analysis demonstrated that the most frequently mutated gene in this cohort was TP53 (detected in 11 out of the 21 tumors) followed by KRAS (detected in 6 out of the 21 patients). The recently discovered potentially targetable MET exon 14-skipping mutation was also detected in 3 patients in our cohort. For the 17 tumors, for, whom RNA-seq was conducted, unsupervised clustering analysis using non-negative matrix factorization (NMF) led to two stable clusters of patients in our cohort. Of particular interest, all patients (7/7) in Cluster 1 have relapsed, while only 3 of 10 patients in Cluster 2 relapsed (p-value < 0.01). Further pathway analyses demonstrated that immune activation pathways are significantly up regulated in tumors from Cluster 2 compared to Cluster 1. Conclusions: SCLs seem to have similar genomic landscape and canonical cancer gene mutations compared to other types of NSCLCs such as squamous cell carcinoma and adenocarcinomas. Immune pathway activation may be associated with lower risk of postsurgical recurrence in patients with localized SCL.
A phase II trial of S-1 plus cisplatin with concurrent proton-beam therapy for locally advanced non-small cell lung cancer.
Authors: Akita Kenji , Iwata Hiromitsu , Ogino Hiroyuki , Yamaba Yusuke , Kunii Eiji , Mori Yuta , Yoshihara Misuzu , Horiuchi Minoru , Hattori Yukiko , Hashimoto Shingo , Nakajima Koichiro , Nakamae Katsumi , Baba Fumiya , Shibamoto Yuta , Mizoe Jun-etsu 
Published: September 2018

e20070 Background: Concurrent chemo-radiotherapy is the standard treatment for locally advanced (LA) non-small cell lung cancer (NSCLC). Recent phase II studies have demonstrated that S-1 plus cisplatin (CDDP) with concurrent radiotherapy yields promising results against LA NSCLC. Proton-beam therapy (PBT) is an alternative modality that is expected to reduce toxic effects against normal tissues compared with X-ray radiotherapy. We conducted a phase II trial of S-1 plus CDDP combined with concurrent PBT for patients (pts) with LA NSCLC. Methods: The eligibility criteria included unresectable stage III NSCLC, chemo-naïve status, PS 0 or 1, and age < 75 years. Pts received CDDP (80 mg/m2) on day 1 and S-1 (30-40 mg/m2 twice daily) on days 1 to 14, q4w, up to 4 cycles, plus concurrent PBT at a total dose of 70 GyE in 35 fractions for primary lesion and 66 GyE in 33 fractions for lymph node metastasis. PBT was performed using respiratory-gated and image-guided techniques, and adaptive plans were implemented according to a verification plan at 10, 20, and 30 days. Results: Thirty-two pts were enrolled between August 2013 and December 2016. The patient characteristics were as follows: median age, 66 (31-74); male/female, 24/8; PS 0, 26 pts; stage IIIA/IIIB, 19/13; non-squamous histology, 17 (53%). Twenty pts were out of indication for radical chemo-radiation with X rays. All 4 cycles of S-1 plus CDDP could be completed in 24 pts and the median number of cycles was 3.3 (range: 2 to 4). Grade 3/4 toxicities per pt were: neutropenia 28%, anemia 13%, thrombocytopenia 9.4%, fatigue, anorexia, esophagitis, mucositis and enteritis 3.1%, and radiation pneumonitis 0%. One case of febrile neutropenia was observed. PR + CR was achieved in 24 of 28 evaluable pts. The median PFS was 12.5 months, and 2-year OS was 63%, with a median follow-up period of 19.5 (range: 1.5-40.0) months. Conclusions: Concurrent chemo-PBT using S-1 plus CDDP with image-guided and adaptive techniques is considered to be effective and well tolerated for LA NSCLC. Further evaluations in a large randomized controlled trial are warranted.
Special considerations of DMCs for oncology studies.
Authors: Kerr David , Koprowicz Kent 
Published: September 2018

e20071 Background: Data Monitoring Committees (DMCs) are an important component of the clinical trial process. They are charged with reviewing interim data and making recommendations to protect the safety of trial participants and ensure the scientific integrity of the study. Oncologists may be involved with the DMC process in a number of ways – as a DMC member, as an investigator, as a sponsor, or in a regulatory role. This presentation will discuss novel aspects of the DMC review process that are particularly relevant for oncology trials. Methods: The authors are leaders of a Contract Research Organization (CRO) that specializes in providing independent DMC services for government and industry sponsored trials. They have worked with hundreds of unique DMCs and facilitated approximately 1,000 DMC meetings. The proposed methodologies for maximizing the efficiency and thoroughness of DMC reviews are based on extensive experience and well-established principles. Results: Topics that will be covered include: Discrepant trends in PFS vs. OS PFS results that are inconsistent between local and central assessment, or are not yet centrally assessed Co-primary endpoints – OS, PFS, ORR, CR Multiple populations of interest – ITT and a biomarker subgroup Interim analyses – overwhelming efficacy and statistical futility Program-wide DMCs – interpreting trends across multiple studies and logistical details Safety assessment in a study with thousands of AEs – novel graphics and tables Laboratory values and vital signs – novel graphics and tables Multiple comparisons and/or multiple p-values Non-standard tables, listings, figures that are particularly useful for DMC review Open-label studies – immediate withdrawals for those randomized to control arm and other potential biases Single-arm studies – how to interpret safety with no control arm Novel therapies – immune-oncology, CAR-T, small sample sizes CIOMS reports or patient narratives Conclusions: DMCs will perform a more thorough and efficient review of accumulating data upon adapting the guidance provided. A more thorough review will enhance the protection of the trial participants while a more efficient review will allow DMCs to focus their efforts appropriately.
A propensity-matched analysis of stereotactic body radiotherapy and sublobar resection for stage I non-small cell lung cancer in patients at high risk for lobectomy.
Authors: Chen Wucheng , Lin Qingren , Sun Xiaojiang , Liu Jinshi , Xu Yaping , Chen Qixun , Mao Weimin 
Published: September 2018

e20076 Background: The aim of this study was to perform a survival comparison between stereotactic body radiotherapy (SBRT) and sublobar resection (SLR) in patients with stage I non-small cell lung cancer (NSCLC) at high risk for lobectomy. Methods: All patients who underwent SBRT or SLR because of medical comorbidities for clinical stage I NSCLC from January 2008 to December 2015 were reviewed retrospectively. Propensity score matching was performed to reduce selection bias between SBRT and SLR patients based on age, gender, performance status, tumour characteristics, pulmonary function. Overall survival (OS) and recurrence-free survival (RFS) were estimated with Kaplan–Meier method. Results: Forty-nine patients were matched into each group of SBRT and SLR (include 27 underwent segmentectomy, 22 underwent wedge resection). There were 32 and 30 men with median age of 67 and 69 years, respectively. Median follow-up was 25 months. In terms of treatment-related mortality, the 30- day mortality rates for the SBRT and SLR groups were 0 and 2.0 %, respectively. Patients treated by SBRT had a tendency to increase 3-year OS compared with SLR (94.0% versus 78.1%; P = 0.064).There was no difference between two groups in 3-year RFS (61.8% versus 65.7%; P = 0.864). In a subanalysis, 3-year OS after SBRT was greatly better than wedge resection subgroup (94.0% versus 67.4%; P = 0.026), but there was no significant difference between SBRT and segmentectomy in 3-year OS (94.0% versus 88.0%; P = 0.212). Conclusions: SBRT had a tendency to increase OS compared with sublobar resection in patients who are not medically fit for lobectomy with clinical stage I NSCLC. However, OS after SBRT was better than wedge resection subgroup. SBRT can be an alternative treatment option to segmentectomy for patients who cannot tolerate lobectomy because of medical comorbidities. A randomized prospective study is necessary to determine survival in compromised SBRT and sublobar resection.
A phase I-II clinical trial to evaluate the safety, pharmacokinetics, and efficacy of high-dose intravenous ascorbic acid synergy with mEHT in Chinese patients with stage III-IV non-small cell lung cancer.
Authors: Ou Junwen , Zhu Xinyu , Lu Yimin , Zhao Changlin , Zhang Hongyu , Zhang Xinting , Zhang Tao , Pang Clifford L.K. 
Published: September 2018

e20078 Background: Ascorbic acid (AA) infusion and modulated electrohyperthermia (mEHT) are widely used by integrative cancer practitioners for many years. However, there are no safety and pharmacokinetics data in Chinese cancer patients. Methods: Blood ascorbic acid in the fasting state was obtained from 35 NSCLC patients; selecting from them 15 patients with stage III-IV entered the phase I-II study. They were randomized allocated into 3 groups. Pharmacokinetic profiles were obtained when they received solely IVAA at concentrations of 1g/kg, 1.2g/kg, and 1.5g/kg, and when IVAA in combination with mEHT. The process was applied 3 times a week for 4 weeks. Participants in the first group received IVAA when mEHT was finished, in the second group IVAA was administered simultaneously with mEHT and in the third group IVAA was applied first, and followed with mEHT. All patients started the trial doses of 1 g/kg for 8 treatments. When there was no DLT observed, the test dose for patients increased to 1.2 g/kg and 1.5 g/kg. DLT was defined as any reversible grade ≥3 adverse events, whether haematological or non-haematological. Results: Fasting plasma AA levels were significantly correlated with stage of the disease. Peak concentration of AA were significantly higher in the simultaneous treatments than in other combinations with mEHT or in solely IVAAmanaged groups. The average scores for the functioning scales continuously increased and the symptoms gradually decrease over the full cycle of the study.3/7 patients with squamous cell lung cancer were CR, 4/7 were PR. 1/8 patient with adenocarcinoma cell lung cancer was PR, 5/8 were SD, and 2/8 were died. Conclusions: IVAA synergies with simultaneous mEHT is safe and the concomitant application significantly increases the plasma AA level for NSCLC patients. QOL is improved when they receive the above treatments. Patients diagnosed with squamous cell lung cancer were sensitive to the above two treatments. Clinical trial information: NCT02655913.
Long-term survival in patients with NSCLC treated with single fraction vs multi-fraction palliative radiotherapy in the case of lung tumor, brain metastases, and bone metastases.
Authors: Szablewska Sylwia , Adamczak-Sobczak Magdalena , Roszkowska Zofia , Roszkowski Krzysztof 
Published: September 2018

e20082 Background: Patients with advanced non-small cell lung cancer (NSCLC) are candidates for different types of treatment, including chemotherapy and radiotherapy or supportive care. Despite the fatal prognosis in advanced disease, many experienced radiation oncologists will apply radiation at low doses with the intention of palliative care. Choosing an effective radiation dose that does not cause significant complications remains under discussion. Methods: We used an extensive database of medical patients diagnosed with NSCLC, treated with palliative radiotherapy at the Oncology Centre in Bydgoszcz, Poland, from June 1998 to December 2013. A group of 3202 patients was divided into subgroups: A) 1762 patients irradiated on the lung tumor (without distant metastases): Total dose: A1) 6 Gy/1 fr.(n = 19); A2) 8 Gy/1 fr.(n = 276); A3) 20 Gy/5 fr.(n = 1349); A4) 30 Gy/10 fr.(n = 118). B) 548 patients irradiated on the central nervous system (CNS) metastases: B1) 20 Gy/5 fr.(n = 476); B2) 30 Gy/10 fr.(n = 72). C) 892 patients irradiated on the bone metastases: C1) 8 Gy/1 fr.(n = 452); C2) 10 Gy/1 fr.(n = 30); C3) 20 Gy/5 fr.(n = 341); C4) 30 Gy/10 fr.(n = 69). Date of death was obtained from medical records. Patients who were alive or whose date of death could not be determined were censored at the date of their last encounter. Survival was calculated from the start of treatment to the date of death or censorship. Results: Overall Survival (in months) for each group was: A1) = 6; A2) = 5; A3) = 7; A4) = 7. B1) = 4; B2) = 4. C1) = 5; C2) = 4; C3) = 4; C4) = 5. There was no significant difference in survival between patients treated with single fraction pRT or multi-fractionation schedules in all groups of patients. Conclusions: The patients who were prescribed single fraction palliative radiotherapy did not have poorer prognoses or experience shorter survival than patients who were prescribed multi-fraction pRT in the case of lung tumor, brain metastases and bone metastases.
A novel MAGE-A1-IgG antibody for lung adenocarcinoma.
Authors: Mao Yuan , Tang Qi , Fan Weifei , Tang Xiaojun , Xu Li , Zhu Jin , Feng Zhenqing , Wang Jun 
Published: September 2018

e20085 Background: Melanoma-associated antigen A1 (MAGE-A1) has been reported to perform oncogenically and act as an ideal candidate in tumor immunotherapy. Methods: One-step quantitative real-time polymerase chain reaction (qPCR) test and immunohistochemistry (IHC) analysis were used to detect the relationship between MAGE-A1 expression and the clinicopathological characteristics of lung adenocarcinoma (LAC). Then a novel MAGE-A1 IgG antibody was constructed on the previous MAGE-A1 scFv antibody by eukaryotic expression vectors. CCK-8, wound healing, transwell, matrigel, apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC) and CDC (complement-dependent cytotoxicity) assays were performed to evaluate the inhibitory effects of MAGE-A1-IgG on LAC in vitro. Results: High MAGE-A1 expression was observed in LAC tissues and MAGE-A1 expression was associated with several malignant properties of LAC patients, including overall survival. MAGE-A1-IgG revealed significant roles in inhibiting proliferation, inducing apoptosis and activating ADCC and CDC of LAC in a dose- and time- dependent manner in vitro. Conclusions: MAGE-A1-IgG may provide a promising therapeutic strategy for the treatment of MAGE-A1-positive LAC.
Adjuvant chemotherapy outcome in unselected single-center non-small cell lung cancer (NSCLC) population.
Authors: Florescu Marie , Blais Normand , Tehfe Mustapha Ali , Gravel Mathieu 
Published: September 2018

e20089 Background: Adjuvant chemotherapy with Cisplatinum/Vinorelbine is an established regimen since a decade in selected resected NSCLC population in order to improve DFS and overall survival. However, the outcome of patients treated outside the research protocols is not as good as in clinical trials. Methods: We retrospectively reviewed 209pts resected stage I to III NSCLC patients using our SARDO database, treated in our University hospital between 2006 and 2015 with a median follow-up of 13mos. Any adjuvant chemotherapy was recorded. Results: Amongst 209 resected NSCLC patients, 185pts (89%) had negative margins and 24pts (11%) have positive margins resection. The observation group and the chemotherapy group in both settings were well-balanced in terms of demographic, co-morbidities and tumor characteristics. As expected, the median overall survival (mOS) in negative margins was significantly better than in positive margins patients (43mos vs 24mos p = 0.029). In negative margins patients, no survival benefit was seen in stage I (A and B) (57 mos for chemo group vs 77 mos for observation group p = 0,217) and stage III (A and B) (39mos mOS for chemo group vs 40mos for observation group, p = 0.37), but a trend for improved mOS was seen in stage II (52 mos for chemo group vs 38 mos for observation group, p = 0.114), also consistent with mPFS results for each group. However, for the small number of patients with positive margins, a significant improvement in survival was seen in chemotherapy arm (mOS 37mos) compared to observational arm (mOS 11mos p = 0,039). No significant difference in survival was seen between Carbo/Taxol regimen and Cisplatinum/Vinorelbine regimen (43 mos vs 38 mos p = 0,658). Conclusions: In our unselected population, adjuvant chemotherapy did not show the improvement in survival expected with margin negative resected NSCLC. In positive resected NSCLC, adjuvant chemotherapy benefit was statistically significant, emphasizing need to treatment to these patients.
Real-world data on treatment patterns and survival among ALK+ NSCLC patients in Japan.
Authors: Nosaki Kaname , Toyozawa Ryo , Taguchi Kenichi , Edagawa Makoto , Shimamatsu Shin-ichiro , Toyokawa Goji , Hirai Fumihiko , Yamaguchi Masafumi , Takeda Yoko , Seto Takashi , Takenoyama Mitsuhiro , Ichinose Yukito 
Published: September 2018

e20505 Background: Three ALK inhibitors (ALKi) are approved in Japan for treatment of patients with ALK-positive (ALK+) advanced or metastatic non-small cell lung cancer (NSCLC). However, the optimal sequence of therapy with ALKi is unclear. The objective of this study was to provide real-world data on the treatment patterns and survival among ALK+ NSCLC patients. Methods: ALK+ patients treated with ALKi in our institute were included in this retrospective analysis. Data on the treatment patterns and outcomes were collected from medical records. Results: In total, 60 patients were included. The median age at the diagnosis was 52.5 years, with 60% female and 65% non-smokers. The first treatment was chemotherapy in 67% and ALKi in 33%. The median overall survival (OS) was 186 weeks. We found differences in the OS for Crizotinib use at any line (118 weeks; presence vs. NR; absence) and first-line use of an ALKi (127 weeks; Crizotinib vs. 416 weeks; Alecitinib or Ceritinib, p = 0.0048). Conclusions: The role of Crizotinib in the treatment of ALK+ NSCLC is decreasing. Alectinib followed by Ceritinib seems to be promising. Treatment decision-making based on a re-biopsy is immature at present. The development of sequential therapy with ALKi based on resistance mechanisms is urgently needed. [Table: see text]