bluuebunny/crossref_metadata_2025_split huggingface dataset:
FOXP3+/CD8+ tumor-infiltrating T-cell ratio as a marker for pathologic response to induction therapy of non-small cell lung cancer.
Authors: Tao Hiroyuki , Shien Kazuhiko , Soh Junichi , Sano Fumiho , Hayashi Tatsuro , Yamamoto Hiromasa , Tanaka Toshiki , Matsuda Eisuke , Toyooka Shinichi , Okabe Kazunori , Sugi Kazurou , Miyoshi Shinichiro 
Published: March 2020

e17517 Background: Survival benefits of induction therapy followed by surgery for advanced non-small cell lung cancer (NSCLC) have been shown. Anti-cancer agents are suggested to mediate cytotoxic effect not only directly on tumor cells but also through the immune system. We investigated the relationship between the status of T-cell differentiation in tumor stroma and pathologic responses to induction therapy in patients with advanced NSCLC. Methods: A total of 69 patients with c-stage IIA to IIIB NSCLC who underwent induction therapy followed by R0 surgery between January 2002 and July 2011 were enrolled. Tumor-infiltrating T cells expressing CD8 or FOXP3 were detected by immunohistochemical staining from biopsy and surgically removed specimens using anti-CD8 antibody and anti-FOXP3 antibody. Staining-positive T cells were counted in 10 fields at 200× magnification of digital images, and then FOXP3+/CD8+ T cell ratio was determined based on the average counts. Results: The mean values of FOXP3+/CD8+ T cell ratio in operative specimens were 1.11 for the patients with pathological no change (p-NC), 0.32 for those with pathological partial response (p-PR), and 0.21 for those with pathological complete response (p-CR) (p = 0.002). There was no association of FOXP3+/CD8+ T cell ratio with gender, histologic types of tumor, or clinical stages. Patients with p-CR showed better relapse-free survival, though statistically no-significant (p = 0.323). Pre-treatment TBLB specimens were available in 12 patients (3 p-NCs, 7 p-PRs, and 2 p-CRs). FOXP3+/CD8+ T cell ratios in operative specimens after induction therapies were elevated compared with that of biopsy specimens in p-NC patients (p = 0.105), whereas the ratios were decreased in p-PR and p-CR patients (p = 0.021). Conclusions: The status of tumor-infiltrating T cell differentiation indicated by FOXP3+/CD8+ T cell ratio was correlated with pathologic response in patients treated with induction therapy followed by surgery for NSCLC. FOXP3+/CD8+ T cell ratio can be a marker for effectiveness of induction treatment.
Prognostic factors and trends in outcome for small cell lung cancer over 20 years.
Authors: Dawe David , Navaratnam Sri , Pitz Marshall W. 
Published: March 2020

e17518 Background: There has been little change in the chemotherapeutic treatment of small cell lung cancer (SCLC) over the last 30 years but changes in radiotherapy have demonstrated a survival benefit in clinical trails. There is substantial disagreement in the literature on whether or not there has been an improvement in survival for SCLC patients and which patient characteristics serve as important prognostic factors. The majority of the data comes from the selective population of patients included in clinical trials, which do not necessarily reflect real world therapeutic effectiveness. Methods: Using the Manitoba Cancer Registry and Manitoba’s physician billing database, we extracted information on all patients receiving a pathologic diagnosis of SCLC in the Canadian province of Manitoba between Jan 1, 1985 and Dec 31, 2004. Linear regression and Cox proportional hazard regression were then used to determine trends in SCLC incidence, survival, sex distribution, treatment, and prognostic factors. Results: Over the course of the study, the number of cases of SCLC diagnosed each year decreased by 1.41 cases/year (p=0.007), due entirely to a decrease in male cases. The proportion of females increased by 1%/year (p<0.001, 95% CI [0.007, 0.013]). In the whole study population, the proportion of patients receiving no antineoplastic treatment increased dramatically with age, from 11.7% in those ≤50 to 50.6% in patients >80 years old (p<0.001). There has been no change in 2 or 5-year survival (p>0.05 at both time points), which is true for both males and females. Two-year survival was 12.7% for females vs 8% for males (p<0.001), and at 5 years 5.3% of females vs 2.6% of males survive (p=0.002). Male sex was a negative prognostic factor with an adjusted hazard ratio of 1.27 (95% CI [1.16, 1.39]). Conclusions: Female sex is a positive prognostic factor in SCLC. In this population based trial, evolution of therapy over 20 years did not translate into improved survival. A further decline solely in the number of male cases may independently improve survival in the future.
Association of decreased expressions of α1,6-fucosyltransferase (α1,6-FT), GDP-mannose-4,6-dehydratase (GMD), and GDP-fucose transporter (GDP-Fuc Tr) with squamous histology in non-small cell lung cancers (NSCLCs).
Authors: Honma Rio , Kinoshita Ichiro , Miyoshi Eiji , Matsuno Yoshihiro , Shimizu Yasushi , Kaga Kichizo , Taniguchi Naoyuki , Akita Hirotoshi 
Published: March 2020

e17520 Background: α1,6-FT, a key enzyme for the core fucosylation of N-glycans, has been shown to be needed for the function of EGF and TGF-β1 receptors. α1,6-FT expression is found in human normal bronchial epithelial cells and bronchial gland cells. However, α1,6-FT expression has not been previously examined in NSCLCs. GMD generates GDP-fucose from GDP-mannose, and is imperative for the synthesis of all fucosylated oligosaccharides. GDP-fucose is transported into the Golgi apparatus by GDP-Fuc Tr to serve as a substrate of FTs. Methods: We examined expressions of α1,6-FT, GMD and GDP-Fuc Tr by immunohistochemistry in 156 surgically resected NSCLCs. Results: High, moderate and low expression of α1,6-FT was found in 25 (16.0%), 35 (22.4%) and 96 (61.6%) NSCLCs, respectively. Multivariate logistic regression analysis for the correlation between α1,6-FT expression and various characteristics revealed a significant association between low α1,6-FT expression and squamous cell carcinomas, as compared with non-squamous cell carcinomas (low vs. moderate, p = 0.0005; low vs. high, p = 0.005). High, moderate and low expression of GMD was found in 32 (20.5%), 32 (20.5%) and 92 (59.0%) NSCLCs, respectively. Multivariate logistic regression analysis for the correlation between GMD expression and various characteristics revealed a significant association between low GMD expression and squamous cell carcinomas, as compared with non-squamous cell carcinomas (low vs. moderate, p = 0.005; low vs. high, p = 0.02). Low expression of α1,6-FT was more prevalent in tumors with low GMD expression than in those with moderate or high GMD expression (p = 0.002). High/moderate, low and no expression of GDP-Fuc Tr was found in 7 (4.5%), 23 (14.7%) and 126 (80.8%) NSCLCs, respectively. Low GDP-Fuc Tr expression was significantly more prevalent in squamous cell carcinomas compared with non-squamous cell carcinomas (p = 0.003). Conclusions: These results indicate that α1,6-FT, GMD and GDP-Fuc Tr may be new markers of NSCLCs with specificity for histology.
Stereotactic body radiation therapy for early-stage non-small-cell lung cancer utilizing a helical intensity modulated image-guided approach.
Authors: Rosen Lane R , Fischer-Valuck Benjamin W , Katz Sanford R. , Durci Michael , Wu Terry , Syh Joseph , Patel Bijal , Syh Jarron 
Published: March 2020

e17524 Background: To report the techniques and results of a large cohort of patients treated with stereotactic body radiotherapy (SBRT) for early-stage non-small-cell lung cancer (NSCLC) using image-guided helical intensity modulated radiation therapy (IMRT) and FDG-PET assisted targeting. Methods: Between February 2005 and August 2010, 79 patients with stage 1 NSCLC were treated with SBRT. 59 patients had T1 tumors and 20 patients had T2 tumors. 62 patients had biopsy proven malignancies and 17 patients were treated empirically based on strong clinical indications. Central tumor location did not disqualify patients. All patients underwent FDG-PET or FDG-PET/CT scanning in the treatment position for planned fusion with a separate kilovoltage (KV) CT simulation. Rigid immobilization was achieved during CT simulation using a double vacuum cast device with abdominal compression. SBRT was delivered via 12 Gy x 4 or 12 Gy x 5 fractionation scheme (48-60 Gy total). Megavoltage CT images were obtained on the treatment unit prior to therapy and repeated mid-fraction with comparison to the KV CT simulation planning images to assure set-up accuracy. Serial follow-up with FDG-PET or FDG-PET/CT studies were performed at 3 months and every 6 months thereafter on all surviving patients. Results: Median patient age was 73 years. Mean tumor size was 2.3 cm (range 0.5 – 6 cm). Median follow-up was 24 months (range 4-78 months). Overall local control rate (LCR) was 94% (95% confidence interval (CI), 86-97%) based on serial FDG-PET. LCR for T1 tumors was 95% vs. 90% for T2 tumors (p = 0.60). Entire cohort overall survival rate (OSR) was 87% (CI, 78-93%) at 1 year and 58% (CI, 47-68%) at 3 years. T1 patients had a 3-year OSR of 71% vs. 43% OSR for T2 patients (p = 0.04). No patients developed life threatening radiation pneumonitis or pulmonary complications. Chest wall pain or rib fracture was reported in 8 patients (10%; CI, 5-19%). Conclusions: Image-guided SBRT with helical IMRT delivered in 4 or 5 fractions of 12 Gy with rigid immobilization and FDG-PET assisted targeting is an effective treatment for early NSCLC and is associated with excellent local control rates and acceptable treatment-related morbidity.
Concomitant chemoradiotherapy phase II study comparing pemetrexed/carboplatin with paclitaxel/carboplatin in patients with unresectable stage III non-small cell lung cancer.
Authors: Ma Shenglin , Xu Yaping , Ji Yongling , Sun Xiaojiang , Zheng Yuanda 
Published: March 2020

e17527 Background: Concomitant chemoradiotherapy is the standard treatment of unresectable stage III non-small cell lung cancer (NSCLC). However, the optimal chemotherapy regimen is still controversial. We have conducted a phase II study to evaluate concomitant treatment using pemetrexed/carboplatin or paclitaxel/carboplatin in these patients. The purpose of this study is to compare the feasibility and activity, and also assess its impact on progression-free survival (PFS). Methods: A total of 37 patients were enrolled between January 2008 and May 2011. Patients received concomitant chemoradiotherapy [thoracic radiotherapy and pemetrexed 500mg/m2, carboplatin AUC 5 every 3 weeks for 2 cycles; or paclitaxel 50mg/m2, carboplatin AUC 2 weekly for 6 weeks. ] Objective response rate according to the RECIST criteria was recorded and toxicity was evaluated using the NCI Common Toxicity Criteria. The Kaplan–Meier method was used to evaluate patient survival. Univariate analysis of patient characteristics and tumor responses was conducted using the Chi-square and Fisher's exact test. Results: The overall response rate for pemetrexed/carboplatin was statistically superior to paclitaxel/carboplatin (P <0.05). In patients with adenocarcinoma, there was a signiﬁcant improvement in PFS with pemetrexed/carboplatin versus paclitaxel/carboplatin (11.6 vs. 9.3 months, respectively). For pemetrexed/carboplatin, rates of grade 3 or 4 neutropenia, anemia, thrombocytopenia, and febrile neutropenia were signiﬁcantly lower (P <0.05), whereas grade 3 or 4 fatigue (P = 0.08) was more common. Conclusions: This data suggests that concomitant chemoradiotherapy with pemetrexed/carboplatin was better tolerability and more efficacy than paclitaxel/carboplatin in a Chinese population with unresectable stage III NSCLC. Better outcomes were observed in patients with adenocarcinoma in pemetrexed/carboplatin. Although the data presented herewith appears more promising in pemetrexed/carboplatin, this study is relatively small, and more data from randomized trials are needed to further validate this regimen.
Outcomes of patients with malignant pleural mesothelioma (MPM) following the approval cisplatin/pemetrexed: Experience of a comprehensive cancer center.
Authors: Jagtap Deepa , Pass Harvey , Baciewicz Frank , Wozniak Antoinette J. , Alvelo-Rivera Miguel , Konski Andre A. , Chen Wei , Smith Daryn W. , Gadgeel Shirish M. 
Published: March 2020

e17528 Background: Mesothelioma is a rare cancer that is estimated to occur in about 2,500 people in the United States every year. MPM is the most common type of mesothelioma. Until 2003 there was no chemotherapeutic regimen approved for the treatment of MPM. The combination of cisplatin/pemetrexed was approved based on improved survival in a randomized phase III study. We analyzed the data of all MPM patients treated at our center, since the approval of this combination, to evaluate the outcomes of these patients. Methods: This retrospective analysis included all patients with MPM evaluated at Karmanos Cancer Institute in Detroit, Michigan, between 2005 to 2010. We analyzed the demographic data, history of asbestosis exposure, histology, clinical stage of diagnosis, treatment received and survival. A multiple Cox regression model was built on age, sex, histology, surgery or not and stage (I&IIvs.III&IV). Results: Fifty-four MPM patients were evaluated between 2005-2010. The median age of patients was 65 years, 70% were males, 74% had known history of asbestos exposure, 76% had epitheloid histology and 63% had stage III/IV disease at diagnosis. Seventy eight percent of patients received pemetrexed based therapy, 50% underwent pleural surgery (EPP-30%, Pleurectomy- 20%) and 37% received radiation therapy as part of the initial therapy. Twenty-one patients underwent surgery following neo-adjuvant chemotherapy. Thirty-nine percent of patients went on to receive second line therapy. The median overall survival was 18 months (95% CI 14- 22). COX model analysis showed that patients with epitheloid histology had a HR of 0.40, p= 0.0168) and patients who were stage I/II had a HR of 0.42, p = 0.0282. Surgery resulted in a HR of 0.66, but it was not statistically significant (p=0.2637). Age and sex were not significantly associated with survival. Conclusions: The median survival of MPM patients in this series was 18 months. As expected epitheloid histology and early stage at diagnosis were associated with improved survival. Surgery did improve survival but this improvement was not statistically significant.
A feasibility study of interventions to improve intraoperative lymph node (LN) collection and pathologic examination of lung cancer resection specimens.
Authors: Ramirez Robert A. , Miller Laura Elizabeth , Wang Christopher Gene , O'Brien Thomas , Khandekar Alim , Schoettle Glenn P , Robbins Samuel G , Robbins Edward T , Gibson Jeffrey B , Osarogiagbon Raymond U 
Published: March 2020

e17531^ Background: The number of LNs examined following lung cancer resection has prognostic value. The International Association for the Study of Lung Cancer (IASCLC) recommends a minimum of 6 LNs and other series have recommended greater than 11. Most resections in the United States fail to meet these recommendations. We hypothesized that simple interventions could improve on the number of LNs examined. Methods: We used a pre-labeled specimen collection kit to aid in collection of N2 LNs and developed a re-dissection protocol to retrieve discarded N1 LNs. We performed a 3 era case control study: Era 1, routine surgical examination (RSE) + routine pathology examination. Era 2, RSE + special pathology examination (SPE). Era 3, SPE + special surgical examination. The Chi-Square, Fishers Exact, Wilcoxon-Mann-Whitney and Kruskal-Wallis tests were used where appropriate for comparisons. Results: Patient demographic and tumor characteristics were similar across three groups. Significantly more N1 and total LNs were examined in eras 2 and 3 compared to era 1 (Table). Significantly more N2 LNs were examined in era 3 compared to eras 1 and 2. There was a non-significant trend toward detection of metastatic LNs. More cases met both IASLC recommendations and had at least 11 LNs examined LNs in eras 2 and 3 compared to era 1. Conclusions: The interventions were feasible and effective in improving LN examination. The number of LNs examined using these interventions exceeded consensus recommendations. A phase III trial incorporating these interventions is being designed. [Table: see text]
Evaluation of soluble mesothelin-related peptide as a marker additional to cytology for diagnosing malignant pleural mesothelioma effusions.
Authors: Vigani Antonella , Ferro Paola , Canessa Pier Aldo , Battolla Enrico , Dessanti Paolo , Manta Carmen , Aschele Carlo , Franceschini Maria Cristiana , Fontana Vincenzo , Fedeli Franco , Roncella Silvio 
Published: March 2020

e17533 Background: Detection of soluble mesothelin-related peptide (SMRP) levels in serum has been proposed to help the diagnosis of malignant pleural mesothelioma (MPM). In this study we evaluated the SMRP levels in pleural effusions of MPM (MPM-PE), the clinical importance and usefulness of SMRP detection in MPM-PE and whether it can have an additional value to cytological analysis (Cyt). Methods: We studied 52 MPM-PE, 129 benign PE (B-PE) and 94 non-MPM pleural metastasis PE (Mts-PE). In all PE samples, both cytology and SMRP detection were performed. SMRP levels were estimated by means of the MesoMark ELISA kit (Fujirebio Diagnostic, Malvern, PA). Diagnostic performance parameters were estimated through the ROC analysis, Youden's index was applied to obtain the best cut-off level and the degree of correlation was estimated by Diagnostic Odds Ratio (DOR) and by P-value (P) with Chi-square test. Results: The median SMRP levels were significantly higher in MPM-PE (28.2 nM) than in B-PE (3.2 nM) or Mts-PE (3.8 nM). MPM-PE vs B-PE yielded an AUC of 84.5 (P<0.001) whereas MPM-PE vs Mts-PE yelded an AUC of 79.6 (P<0.001). The cut off level in MPM-PE was estimated in 9.30 nM at which value we established Se=75%, Sp=93% for MPM-PE vs BPE and SP=81% for MPM-PE vs Mts-PE. We found SMRP positive cases (≥ cut off) in 38/52 (73%) MPM-PE, in 9/129 (7%) B-PE (DOR=40, P<0.001) and in 18/94 (19%) Mts-PE (DOR=13, P< 0.001).Cyt was negative in 29/52 (56%) of MPM-PE, among which SMRP was positive in 20/29 (69%) cases. Cyt was positive in 15/52 (29%) of MPM-PE, among which SMRP was negative in 4/15 (27%) cases. Finally, in 8/52 (15%) MPM-PE Cyt diagnosis was suspicious and SMRP was found positive in 7/8 (88%) cases. Conclusions: Our results demonstrate that SMRP levels in PE are significantly higher in MPM-PE than in PE from other pathologies. However the test cannot be alternative to cyt but it may provide additional diagnostic value to Cyt. SMRP detection in MPM-PE can be applied in the workup of patients with a PE of unknown origin.
Frequency of actionable genomic alterations in early-stage lung adenocarcinoma (LA) detected by next-generation sequencing (NGS).
Authors: Wang Kai , Stephens Philip , Yelensky Roman , Ross Jeffrey S. , Miller Vincent A. , Dracopoli Nicholas J , Cronin Maureen T. , Platero Suso J. 
Published: March 2020

e17541 Background: Early stage LA (≤T1N0) has a variable natural history. Although many patients are cured (~2/3) with surgery, many tumors recur and better methods are needed to distinguish these subsets and tailor therapy accordingly. We undertook a pilot study of NGS in such tumors to characterize the frequency and diversity of actionable genomic alterations in this setting. Methods: Formalin-fixed paraffin embedded (FFPE) tissues from 21 archival samples collected from 2007 to 2011 were obtained commercially with accompanying clinical and pathologic data. Clinical characteristics: female (17)/male (4); T1N0 (18), AIS (2), MIA (1). Pathologic LA subtype: acinar (n=8), mucinous (n=4), lepidic (n=4), and mixed (n=2) in addition to AIS (n=2) and MIA (n=1). Targeted NGS performed in a CLIA laboratory (Foundation Medicine) gave evaluable results in all cases. Genomic libraries were captured for 3230 exons in 182 cancer-related genes plus 37 introns from 14 genes often rearranged in cancer and sequenced to average median depth of 640X with 99% of bases covered >100X. Results: Forty-one driver mutations were identified in 17 genes among the 21 patients (avg= 1.9) including 28 base substitutions, 5 indels, 4 amplifications, 3 homozygous deletions and 1 rearrangement. Notably, 90% of cases (19/21) harbored at least one alteration that can be classified as actionable-linked to an approved therapy in LA or another tumor type or a clinical trial. Examples include alterations in EGFR (n=6), NF1 (n=2, PI3K/mTOR inhibitors), CDNK2A (n=1, CDK inhibitors), EML4-ALK (fusion, n=1, ALK inhibitor), ERBB2 (n=1, TKI inhibitors), STK11 (n=1, mTOR inhibitors), and MDM2 (n=1, nutlins). Conclusions: NGSidentified drivergenomic alterations in T1N0 LA, MIA and AIS. On average, two known driver mutations were identified per tumor, many of which are associated with existing or emerging targeted therapies. This provides rationale for future investigation of larger series of T1N0 LA, AIS and MIA, using NGS to evaluate the prognostic value of these changes and could presage adjuvant trials in higher risk patients.
A phase II study of cisplatin (CDDP) and oral vinorelbine (NVBO) concomitantly with radiotherapy (RT) in locally advanced (LA) non-small cell lung cancer (NSCLC) treatment: Interim analysis.
Authors: Juan Vidal Oscar , Vazquez-Estevez Sergio , Giner Vicente , Casal Rubio Joaquin , Firvida Jose-luis , Aparisi Francisco , Muñoz-Langa José , Garcia Sanchez Jose , Girones Regina , Perez Francisco Javier , Sanchez-Hernandez Alfredo 
Published: March 2020

e17545 Background: CDDP+NVBO as induction and concomitant regimen with RT has shown good efficacy outcomes and safety profile (Krzakowski, J Thor Oncol. 2008). The objective of this study was to evaluate the effectiveness and toxicities of the combination of CDDP and NVBO given at full doses concomitantly with RT in LA-NSCLC. Methods: Between February 2010 and May 2011, 26 chemo-naive patients (p) with histologically confirmed stage IIIA/IIIB unresectable LA NSCLC were treated. Treatment consisted of 4 cycles (cy) of NVBO 60 mg/m2 on days 1 and 8 and CDDP 80 mg/m2 every 3 weeks plus RT 66 Gy starting on day 1, cy 2. A standard Fleming two stage design is being used. The sample size is calculated with a power of 90% and a two-sided type 1 error allowance of 5%. Stage 1 included 25 pts, with subsequent expansion to a total of 45. Results: Patient’s characteristics were: Median age, 59 years (range 48-71); males, 92%; smokers, 60%; adenocarcinoma, 28% / squamous, 64%; stage IIIA, 54% / IIIB, 46%. 21 p completed the 4 cy treatment as per protocol. We analyzed 92 cy. Hematological toxicities (% cy): grade (g) 3/4 neutropenia, 42.3%; g3 anemia, 3.3%; g3 thrombocytopenia, 2.2%; febrile neutropenia, 1 p. Non-hematological toxicities (% cy): g3 oesophagitis, 6.5%; g4 diarrhea, 1.1%. 21 p were evaluable for response. 1 CR (4.8%), 17 PR (81%) and 1 SD (4.5%) were reported. ORR 85.8%. Survival analysis has not been performed due to short follow-up. Conclusions: The findings of this interim analysis confirm the previously reported outcomes of efficacy and safety with NVBO plus CDDP when administered concurrently with RT in stage IIIA/IIIB p. The trial has met the criteria for continuation into stage 2.