bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted radiopeptide therapy Re188-P2045 to treat neuroendocrine lung cancer.
Authors: Adams Christopher Peter , Saif Wasif M. 
Published: September 2018

e20016 Background: : Despite the recent success of checkpoint inhibitors, there continues to be a significant medical need for lung cancer therapies that can be directed to the patients most likely to respond. Somatostatin receptor subtype 2 (SSTR2) is the most widely up-regulated subtype in both small and non-small cell lung cancers and is also expressed in tumoral (but not mature) blood vessels. Peptide targeted radiotherapy has advantages over traditional targeted therapies in that targeted tumor cells as well as surrounding cancer cells and supporting stroma are selectively killed. This study was conducted to determine the ability of Rhenium Re 188 P2045, a radiolabeled somatostatin analog specific for SSTR2 to both image (to select the most appropriate patients) and treat lung cancer patients who over-express somatostatin receptors. Methods: In an open label, single arm study, refractory lung cancer patients to standard of care therapy were identified by image analysis using Rhenium Re 188 P2045, a radiolabeled somatostatin analog. 25 Patients received the imaging dose of 10uCi of Re188 and 265ng of peptide by intravenous injection. Three patients were selected based on high SSTR expression levels to receive 30uCi of Re188 P2045 as a therapeutic dose 14 days after imaging. Patients were followed for 8 weeks post treatment. Results: The imaging study revealed a high density of expression of the somatostatin receptor in the lungs of patients. Patients in the imaging and therapeutic treatment groups reported no adverse advents or signs of toxicity. The image analysis using Re188 P2045 was compared to CT images and demonstrated accurate detection of lung tumor lesions. The images obtained using Re188 P2045 were of sufficiently high quality to enable identification of receptor expression at the tumor site as shown in Figures 1&2. Conclusions: Rhenium Re 188 P2045, a radiolabeled somatostatin analog, may be used to both identify and treat lung cancer tumors. The ability to image and dose patients with the same targeted molecule enables a personalized medicine approach and this highly targeted patient therapy may significantly improve treatment of tumors that over express somatostatin receptor.
Predicting tumor-immune response to checkpoint inhibitors using a novel patient-derived live tumor explant model.
Authors: Radhakrishnan Padhma , Goldman Aaron , Ulaganathan Baraneedharan , Thaya Kumar Allen , Maciejko Laura , Gertje Hans , Shanthappa Basavaraja U , Mehrotra Debapriya G G , Biswas Manjusha , Thiyagarajan Saravanan , Majumder Biswanath 
Published: September 2018

e20035 Background: Immunotherapy has emerged as a powerful treatment paradigm wherein therapies primarily target immune components. For example, blockade of PD-1 and PD-L1 offers effective treatment options for patients with aggressive tumors such as head and neck squamous cell carcinoma (HNSCC) and in non-small cell lung carcinoma (NSCLC). However, clinical responses to immotherapy vary widely among patients. There is an unmet need to understand these disparities at the individual patient level. Rationally combining checkpoint inhibitors may address many of these underlying challenges. Methods: Here, we describe a patient-derived ex-vivo platform technology CANscript™, which captures the 3D profiles of native tumor microenvironment by incorporating tumor tissue, autologous immune cells, and immune-targeted agents. Utilizing late stage HNSCC and NSCLC patient tumors we interrogated the phenotypic changes in the tumor-immune contexture in response to standard-of-care agents, PD-1 and PD-L1 inhibitors. Flow cytometry and immunohistochemistry profiling of CD8, CD45, FOXP3, CXCR4, CD68, PDL1, PD1), cytokine profile (IL6, IL8, IFN-g, IL12 and others), and tumor proliferation/apoptosis were measured. Results: The data suggest that PD-1 and PD-L1 blockade induced patient-specific response, which was characterized by differential distribution and infiltration of CD8+ and CD4+ lymphocytes, distinct patterning of cytokines linked to functional dysregulation, and changes in tumor proliferation and apoptosis. Interestingly, the data demonstrated unique immune signatures associated with single agent vs. combination therapy that imply functionally distinct mechanisms of orchestration of response. Conclusions: Our data highlights the translational underpinnings of of CANScript™ as an ex vivo platform for predicting patient driven therapeutic response of immune checkpoint inhibitors where distinct tumor-immune networks influence clinical response to therapy. Information obtained from this study can re-shape our understanding of patient selection and rational combinations for novel immune checkpoint inhibitors.
Real-world data evaluating the value of PET-CT for mediastinal staging in patients diagnosed with non-small cell lung cancer in an area with high prevalence of granulomatous diseases: The LACOG-0114 study.
Authors: Fritscher Carlos Cezar , Zanini Mara Lise , Berdichevski Eduardo Herz , Vilas Eduardo , Hochhegger Bruno , da Silva Vinicius Duval , Pinto José Antônio Figueiredo , Fritscher Leandro Genehr , Hartmann Louise , Alba Marcos , Sartori Guilherme Parisotto , Matushita Cristina , Vieira Arthur , Bortolotto Vanessa Rezende , do Amaral Rayssa Ruszkowski , Zaffaroni Facundo , Martínez-Mesa Jeovany , Werutsky Gustavo , Barrios Carlos H. , Debiasi Marcio 
Published: September 2018

e20065 Background: Evaluation of the mediastinum is critical for therapeutic decision in patients with operable non-small cell lung cancer. This analysis aims to evaluate specificity and positive predictive value (PPV) of PET-CT in mediastinal staging of patients diagnosed with NSCLC in South Brazil, an area with high prevalence of infectious granulomatous disease, such as tuberculosis (estimated incidence of 45 cases/100.000 and only 63.7% of cure rate) (http://www.saude.rs.gov.br/upload/1459169540_RELATÓRIO%20TUBERCULOSE%202016.pdf). Methods: Patients with stages I-III NSCLC underwent 18FDG PET-CT before invasive mediastinal staging. Different SUV cut-offs were evaluated, but for the purpose of this analysis were considered positive all PET-CTs showing any mediastinal uptake > 5 SUV. This abstract shows the specificity and the PPV associated with PET-CT when this high-uptake cut-of is considered. Results: From Aug/2014 to Aug/2016, 100 patients were enrolled, all treated at the Brazilian Public Health System, of which 85 were submitted to mediastinoscopy after PET-CT. Median age was 65 years (range 47-80). At baseline, 49 (58%) patients were male and 68 (80%) white. Current or former smokers accounted for 94% (80/85) of the sample. The prevalence of mediastinal involvement was 27% (23/85) confirmed by histopathological evaluation. PET-CT showed specificity of 79% (95% CI 67%–88%) and PPV of 54% (95% CI 40%–67%) when a SUV > 5 was used as cut-off for positivity (see table). Conclusions: These findings consolidate the clinical impression that a positive PET-CT does not confirm the diagnosis of mediastinal involvement in NSCLC patients treated in areas with high prevalence of infectious granulomatous diseases. In this scenario, all positive findings should be confirmed with histopathological evaluation to assure the diagnosis. Clinical trial information: NCT02664792. [Table: see text]
Concurrent chemoradiation (CChRT) for locally advanced stage III non-small cell lung cancer (NSCLC) with cisplatin and vinorelbine and thoracic radiotherapy: A phase II study from the Galician Lung Cancer Group.
Authors: Gomez Garcia Susana , Costa Rivas Marinha , Areses Manrique Mª Carmen , Fernández Núñez Natalia , Garcia Jorge , Caeiro Manuel , Castro Enrrique , Formoso Ines , Calvo P , De Dios Alvarez Noemi , Firvida Jl , Campos Begoña , Azpitarte Cristina , Afonso Francisco Javier , Amenedo Margarita , Casal Rubio Joaquin 
Published: September 2018

e20067 Background: Platinum-based CChRT is recommended as the evidence-based approach for the management of patients (p) with locally advanced stage III NSCLC and a good performance status, although a clearly superior regimen has not been identified. The aim of our study was to evaluate the effectiveness and toxicities of CChRT with Cisplatin (C) and intravenous and oral vinorelbine (V) and thoracic radiotherapy. Methods: 39 p with histologically confirmed inoperable locally advanced NSCLC, stage IIIA (T4 or N2)/IIIB, PS 0-1 and adequate lung function (FEV1 > 1.1, V20 < 30%) were included in CChRT with: C 80 mg/m2 day 1 and intravenous V 25 mg/m2 day 1 and oral V 60 mg/m2 day 8 for three cycles, during conformal radical thoracic radiotherapy (66 Gys, 180 cGy/day). The primary objective was overall survival (OS); secondary objectives were progression free survival (PFS), response rate (RR) and toxicity. Median follow-up: 20,4 months. Results: The p characteristics were: mean age 69,8 years (44-75); male/female: 33/6; ECOG PS 0/1: 7/32; adeno/squamous/large cell carcinoma: 20/13/6; stage IIIA 19 p and stage IIIB 20 p. All p were evaluable for response and toxicity. RR: 3 CR, 27 PR (RR 77%; 95% CI: 64-90), 5 SD (12.8%) and 4 PD (10.2%). The median PFS was 12 months (95% CI: 7-17) and median OS was 36 months (95% CI: 14-58). The PFS at 1/3 years were 46%/22% and the OS at 1/3 years were 75%/47%. Main toxicities (NCI-CTC 4.0) per p in CChRT (109 cycles of chemotherapy, 2.9 per p; mean doses RT: 65,3 Gys) grade 1-2/3-4 (%) were: neutropenia 32.4/25.6; anemia 32.4/10.8; thrombocytopenia 13.5/2.7; nausea/vomiting 27/2.7; fatigue 28.2/0; esophagitis 43.5/5.4 and pneumonitis 17.9/0; hospitalizations were necesary in 13 p: the most important were febrile neutropenia (6 p) and grade 3 esophagitis (2 p). Conclusions: CChRT with Cisplatin and intravenous and oral Vinorelbine during thoracic radiotherapy is a feasible treatment option for inoperable locally advanced stage III NSCLC, showing good clinical efficacy and tolerability with excellent long-term survival.
Spatio-temporal distribution of lung cancer mortality rate in Peru: 2005-2014.
Authors: Flores Claudio J. , Torres-Roman Junior S , Mas Luis , Ruiz Mendoza Rossana Esther , Samanez Cesar Augusto , Aguilar Alfredo , Vallejos Sologuren Carlos 
Published: September 2018

e20081 Background: Lung cancer still remains as the principal death cause in many regions around the world. Its mortality varies according to the regions and study periods. In Peru it represents the sixth most frequent malignant neoplasm and the fourth cause of cancer related death. We reported the spatial autocorrelation and the temporal variation in lung cancer mortality rate in Peru. Methods: Data of lung cancer mortality in Peru between 2005-2014 was obtained from the Ministry of Health. Information on the number of inhabitants was obtained from National Institute of Statistics and Informatics. Age standardized mortality rate (ASMR) was calculated based on the 2011 world standard population. Spatial autocorrelation was determined according to Moran’s Index and the Local G Cluster Map to explore the cluster patterns between regions. Results: During the study period 16,839 deaths due to lung cancer were reported. The lung cancer mortality rate in Peru increased from an ASMR of 12.8 (95% CI: 11.9-13.7) by 100,000 persons in 2005 to 13.4 (95% CI: 12.5-14.3) in 2014. According to the quartiles, the ASMR was higher in the north, south and east, and lowest in others regions. The spatial distribution of the ASMR showed a significant spatial autocorrelation (Moran´s I: p = 0.025). Also, during the study period, the ASMR showed a significant increase and decrease in some regions and in others it was constant. Conclusions: In Peru, lung cancer mortality rate showed a spatial and temporal variation in different regions. The increase in mortality rate in some regions requires identification of risk factors in order to establish public measures to reduce the risk of lung cancer mortality.
The impact of four dimensions CT simulation on planning target volume in radiotherapy for primary lung cancer.
Authors: Abuhijla Fawzi Jamil , Hammoudeh Lubna Abdelrahman , Abu-Hijlih Ramiz Ahmad , Khader Jamal 
Published: September 2018

e20091 Background: 4D CT simulation has been evolved to estimate the internal body motion and considered as a useful tool for intra-thoracic tumor definition. This study aimed to evaluate the impact of using 4D simulation on the planning target volume (PTV) for primary lung tumor. Methods: Patients who underwent CT simulation for primary lung cancer radiotherapy between 2012-2016 using 3D- (free breathing) and 4D- (respiratory gated) institutional protocol were included in this retrospective review. For each patient, gross tumor volume (GTV) was contoured in free breathing scan (3D-GTV), exhale scan (e-GTV) and inhale scan (i-GTV). The corresponding CTVs (3D-CTV, e-CTV and i-CTV) were created by adding 1 cm in all directions. 3D-internal target volume (3D-ITV) was generated by 0.5 cm cranio-caudal expansion of 3D-CTV, while 4D-ITV was created by combination of e-CTV and i-CTV. Subsequently, a 0.5 cm margin was added to generate the 3D-PTV and 4D-PTV respectively. The volumes of 3D-PTV and 4D-PTV were compared to examine the impact of 4D CT simulation on changes in the volume of PTV. Univariable and multivariable analysis were performed to test the impact of volume and location of GTV on the changes of PTV volume by more than 10 % between free breathing and respiratory gated scans. Results: A total of 10 patients were identified. The median [range] GTV, i-GTV, e-GTV volumes were 13.55 [1.44-628.66], 13.17 [1.77-627.36], 12.85 [1.34-630.25] cc respectively. The 3D-CTV, i-CTV, e-CTV volumes were 86.37 [23.76-1209], 84.97 [25.5- 1220.4], 83.40 [23.36-1224.12] cc respectively. 3D-ITV and 4D-ITV median volume was 106.06 [3.99-1422.8], 88.02 [20.51-1338.18] cc respectively. 3D-PTV was significantly larger than the 4D-PTV; median [range] volumes were 182.79 [58.65- 1861.05] vs. 158.21 [52.76-1771.02] cc, p = 0.0068). On multivariable analysis, neither the volume of GTV (p = 0.4917), nor the location of the tumor (peripheral, p = 0.4914 or lower location, p = 0.9594) had an in impact on PTV differences between free breathing and respiratory gated scans. Conclusions: The use of 4D simulation reduces the PTV for primary lung cancer, and it should be routinely implemented in clinical practice regardless the tumor volume or location.
Brigatinib (BRG) in patients (pts) with crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC) and brain metastases in the pivotal randomized phase 2 ALTA trial.
Authors: Ou Sai-Hong Ignatius , Tiseo Marcello , Camidge D. Ross , Ahn Myung-Ju , Huber Rudolf M. , Hochmair Maximilian J. , Kim Sang-We , West Howard Jack , Reckamp Karen L. , Molina Julian R. , Liu Geoffrey , Delmonte Angelo , Viteri Ramirez Santiago , Bearz Alessandra , Summers Yvonne J. , Reichmann William , Kerstein David , Gettinger Scott N. , Kim Dong-Wan 
Published: September 2018

e20502 Background: The CNS is often a site of first disease progression in CRZ-treated ALK+ NSCLC. The ALTA trial is assessing BRG, an investigational next-generation ALK inhibitor, in pts with CRZ-refractory advanced ALK+ NSCLC, including pts with baseline brain metastases. Methods: In ALTA (NCT02094573), pts were stratified by presence of baseline brain metastases and best response to prior CRZ and randomized 1:1 to receive BRG at 90 mg qd (arm A) or 180 mg qd with a 7-d lead-in at 90 mg (arm B). Here, we show data for pts with baseline brain metastases. An independent review committee (IRC) assessed intracranial efficacy. Results: Of 222 pts (112 in arm A; 110 in arm B), 80 (71%)/74 (67%) in A/B had baseline brain metastases per investigators, with median age 49/55 y; 74%/76% had received chemotherapy. As of May 31, 2016, 51%/59% of these pts continued to receive BRG in A/B; median follow-up was 9.6/11.4 mo. Intracranial efficacy is shown in the table. Among these pts, most common treatment-emergent adverse events were: nausea 35%/46% (A/B), headache 30%/31%, vomiting 29%/31%, diarrhea 21%/38%, cough 25%/32%; grade ≥3: increased blood CPK 1%/12%, hypertension 4%/7%, increased lipase 4%/3%. Conclusions: BRG yielded substantial intracranial responses with robust iPFS and acceptable safety in ALK+ NSCLC pts with baseline brain metastases in ALTA. 180 mg (with lead-in) showed consistently improved intracranial efficacy compared with 90 mg. Clinical trial information: NCT02094573. [Table: see text]
Mutual transformation between adenocarcinoma and squamous carcinoma after EGFR tyrosine kinase inhibitors treatment in lung cancer.
Authors: Ying Zheng ming 
Published: September 2018

e20510 Background: Knowledge on the epidermal growth factor receptor (EGFR) has improved survival of non-small cell lung cancer (NSCLC). Several mechanisms underlying have been discovered, here we would report a rare resistant mechanism of histology mutual transformations. Methods: From July 2013 to June 2015, we retrospectively collected 135 NSCLC patients who were in resistance with TKI treatments. Patients’ clinical data including pathologic result, gene status, demographic information, clinical staging, and treatment were recorded. [YL1] Results: Among the 135 NSCLC patients, we found two cases of lung cancer with histological transformation from adenocarcinoma to squamous cell carcinoma, one case from squamous cell carcinoma to adenocarcima after TKI treatment. These cases still harbored sensitive epidermal growth factor gene mutations and developed acquired resistance T790M mutation. Conclusions: Histologic evolution may be a mechanism associated with TKI resistance .
Fully automated and sensitive detection of EGFR exon 18, 19, 20 and 21 mutational status in <2.5 hrs from a single FFPE slice.
Authors: Sablon Erwin , Reijans Martin , Vandercruyssen Genevieve , Keuleers Inge , Helsens Kenny , Vandesteene Charlotte , Elsen Natasja , Peelman Natania , Vandenbroucke Ina , Maertens Geert G. 
Published: September 2018

e20519 Background: Current molecular testing for mutations and indels in EGFRexons 18, 19, 20 and 21 is still laborious and often requires > 5 days in specialized labs. Multiple slices of FFPE tissue are often needed. Lack of experience, time or tissue for molecular testing are among the reasons why patients are often deprived of the proper targeted therapies. Therefore, a fast and fully automated assay with minimal hands-on time which can handle small samples should allow laboratories to quickly generate EGFR testing results as part of their precision medicine report. Methods: Idylla is a fully integrated MDx platform that combines speed and ease of use with high sensitivity and high multiplexing capabilities. For EGFR testing, it overcomes the current problem of lack of tissue and the time-consuming step of processing FFPE tissue samples. After insertion of a single 5 µm FFPE slice containing ≥10% neoplastic cells into the cartridge, the complete process of liquefication, extraction, rtPCR, data analysis and reporting is fully automated and takes < 2.5 hours. The Idylla EGFR Mutation Assay (RUO) allows the sensitive detection of 50+ mutations including indels in exons 18, 19, 20 and 21. Results: The Idylla EGFR Mutation Assay (RUO) was tested with single FFPE slices from 280 clinical NSCLC samples with known mutations as analyzed by NGS and digital droplet PCR. It demonstrated excellent specificity and sensitivity with an overall percentage agreement of > 96% and a positive and negative percentage agreement of > 97% and > 95%, respectively. Analytical sensitivity was assessed using cell line derived materials embedded in paraffin containing defined ratios of mutants and dilutions thereof in a WT background. Allelic frequencies ranging from 1 to 10% were tested in 6-fold and showed analytical sensitivities of 1% for all except one target which showed a sensitivity of 5%. Turnaround time of a run was < 2.5 hours and hands-on time was < 2 min. Conclusions:The new and fully automated Idylla EGFR Mutation Assay (RUO) demonstrates excellent specificity, high sensitivity, ease of use combined with a fast turnaround time for complete testing of more than 50 relevant EGFR mutations on FFPE samples from NSCLC patients.
Level of activated circulating endothelial cells to predict progression-free survival of Anlotinib treatment in patients with NSCLC: Analysis on ALTER-0303 study.
Authors: LI Kai , Wang Jing , Wang Xinyue , Liu Zhujun , Zhang Cuigui , Chen Peng , Meng Zhaoting , Chen Jinliang , Huang Chun , Jiang Xiangli , Liang Yan , Lin Li , Jiang Richeng , Wang Liuchun 
Published: September 2018

e20530 Background: Activated circulating endothelial cells (aCECs) have been indicated as a potential biomarker of angiogenesis in a variety of cancers. Several studies have revealed that aCECs may reflect the extent of tumor angiogenesis, and the level of aCECs counts may has correlation with progression-free survival (PFS) in anti-angiogenesis therapy on NSCLC patients. Therefore, we investigated the association between aCECs and PFS of Anlotinib treatment in ALTER-0303 study. Methods: NSCLC patients with aCECs counts in ALTER-0303 study were observed. Samples were prospectively collected at six time points: before treatment (baseline), on the 7th, 15th, 21th, 42th, 63thday of Anlotinib treatment. aCECs was identified by Flow cytometry (FCM). The prognostic value of aCECs counts was analyzed and, the patients were stratified according to their ratio of the minimum aCECs counts in all time points and counts on baseline (aCECs min/baseline) as <1 and ≥1. Results: Forty-nine patients were included of which 35 and 14 had an aCECs min/baseline<1 and ≥1, respectively in Anlotinib arm. Median follow-up was 8.6 months. In univariate survival analysis, patients with min/baseline<1 had longer PFS [HR=0.439, 95% CI (0.211-0.912), P = 0.023], the median PFS for the patients with aCECs min/baseline <1 and ≥1 were 193 days and 124 days, respectively (shown in Table). However, there were no significant relation between PFS and such aCECs min/baseline ratio found in control arm of ALTER-0303 study. Conclusions: A decrease of aCECs counts from baseline during an initial period of Anlotinib therapy may predict longer PFS and good response in NSCLC patients. Information: NCT02029209, NCT02388919 Clinical trial information: NCT02029209. [Table: see text]