tbuckley/cabot-search huggingface dataset:
Abstract 16750: Heritability of Telomere Length and Interaction of Longevity Locus With Smoking in African American: the Jackson Heart Study
Authors: Stanford Mwasongwe, Alex P Reiner, Laura Raffield, Adolfo Correa, Mario Sims, James G Wilson, Solomon K Musani
Journal: Circulation (2017)

Background: Leukocyte telomere length (LTL) is associated with aging and longevity, as well as lifestyle factors such as smoking and socioeconomic status. In a large sample of related African Ameri...
Theoretical foundation of early intervention for chronic obstructive pulmonary disease
Authors: Guochao Shi
Journal: BMJ (2018)

慢性阻塞性肺疾病(慢阻肺)是一种常见的慢性气道疾病，晚期慢阻肺不仅对人类健康造成严重危害，而且临床疗效也受到严重影响，因此早期干预已成为慢阻肺防治的焦点。需要强调早期慢阻肺是一个时间概念，不应与轻度慢阻肺混淆。与晚期慢阻肺相比，虽然早期慢阻肺患者更多，但更容易被忽视，更多被漏诊。早期慢阻肺对人类健康同样可造成严重危害，包括急性加重，肺功能、活动能力和生命质量下降，医疗负担增加，疾病进展等。早期慢阻肺最早期的病理变化是外周气道炎症反应，该期别的疾病仍然是可逆的；一旦气道壁和肺实质出现结构异常，疾病治疗效果明显受到影响。虽然如此，目前我们已经有早期干预的措施，仍能阻止疾病的进展，这是我们早期干预的基础。积极提高人们对慢阻肺的认知是慢阻肺早期干预的关键。
Association of LINC00858 with clinical outcome of patients with cervical cancer who received standard concurrent chemo-radiotherapy.
Authors: Shun Lu, Siyao Deng, Jiayu Zhang, Jin Yi Lang
Journal: Journal of Clinical Oncology (2020)

e18002 Background: Cervical cancer is the second most common malignant tumour threatening women’s health and remains a vast challenge for many underdeveloped nations. Combination of concurrent chemotherapy with external beam radiation therapy (EBRT) followed by intracavitary brachytherapy (ICBT) boost achieved a favorable outcome for cervical cancer patients. However, the reduced sensitivity of cancer cells to radiotherapy is an important cause of re-currence and metastasis in some patients, it is necessary to constantly improve the radiotherapy technology and the treatment effect. Long noncoding RNAs (lncRNA) are noncoding RNA molecules greater than 200 nucleotides in size that are often critical regulators of gene expression, lncRNAs were implicated in stem cell pluripotency by examining the expression. Methods: Whole-exome sequencing and RNA sequencing were conducted in patients with locally advanced cervical cancer (LACC) to identify prognostic variants by using a two-stage case-control design. Patients developed local recurrences in 3 years after standard concurrent chemotherapy with EBRT followed by ICBT were divided in case group. While patients did not show local recurrences were regarded as a radio-sensitive group. In the first stage, DNA and RNA were extracted from formalin-fixed paraffin-embedded tumor tissues of 32 patients. In the second stage, to validate the significant association between LincRNA and Local control rate of patients found in first stage, RT-PCR was carried out in RNA samples from an independent 100 patients (with same criteria of selection). Cox regression models were used to analyze the association between genetic variants and time-to-event outcomes. Results: In the first stage, expression of 7 LincRNAs: RP11-335O4.(P = 0.01,HR = 10.86), CTD-2292M14.1(P = 0.01,HR = 9.47),RP11-94H6.1(P = 0.02,HR = 9.47), RP11-417L19.2(P = 0.0,HR = 9.36), RP4-683M8.2(P = 0.02,HR = 10.82), RP11-20B24.3(P = 0.02,HR = 8.90) and LINC00858(P = 0.03,HR = 6.41) were found to be markedly correlated with relapse-free survival in 32 patients. Among these LincRNAs, LINC00858 (P = 0.01, HR = 11.23) remained significant association with relapse-free survival in 100 independent patients. Conclusions: Our data suggest that LincRNA may be a useful predict marker for radiosencetivity of cervical cancer patients.
Consolidate the basis for heart failure management through enhancing professional education at grassroots levels in China
Authors: Yuhui Zhang, Jun Huang
Journal: BMJ (2019)

简要介绍《急性心力衰竭基层诊疗指南（2019年）》和《慢性心力衰竭基层诊疗指南（2019年）》撰写工作的背景和意义，指出指南从基层医疗卫生机构的实际工作出发，在心力衰竭早期识别与诊断、转诊和社区管理、患者自我管理和家庭管理方面给出了明确的指导。
Randomized phase I trial to evaluate <i>C</i>oncurrent <i>o</i>r <i>S</i>equential <i>I</i>pilimumab, <i>N</i>ivolumab, and stereotactic body <i>R</i>adiotherapy in patients with stage IV non-small cell lung cancer (<i>COSINR Study</i>).
Authors: Jyoti D. Patel, Christine M. Bestvina, Theodore Karrison, Michael J. Jelinek, Aditya Juloori, Kelli Pointer, Philip C. Hoffman, Sean P. Pitroda, Everett E. Vokes, Steven J. Chmura
Journal: Journal of Clinical Oncology (2020)

9616 Background: Stereotactic body radiotherapy (SBRT) provides high rates of treated metastasis control, stimulates innate and adaptive immune pathways, and is safe in patients treated with anti-PD1 monotherapy following SBRT. We hypothesize that SBRT may improve outcomes for patients receiving immunotherapy through both direct cytoreduction and increased immunogenicity. Within this context, we conducted a phase 1 trial designed to evaluate the safety of combination immune checkpoint blockade with nivolumab and ipilimumab(N/Ip) plus sequential (Seq) or concurrent (Con) multisite SBRT (mSBRT) in patients with stage IV NSCLC. Methods: Treatment naïve patients (EGFR/ALK WT) with advanced NSCLC received SBRT to 1 to 4 metastases. Not all metastases were targeted, and metastases &gt; 65 mL were partially irradiated. Brain metastases were allowed on protocol, and those &gt; 3mm were treated prior to enrollment. SBRT dose varied by anatomic site and ranged from 45 to 50 Gy in 3 to 5 fractions with predefined dose de-escalation if excess dose-limiting toxicities were observed. Patients on Seq arm received N/Ip between 1-7 days after completion of SBRT. Patients in Con arm received N/Ip prior to completion of SBRT. N/Ip continued until progression, development of toxicity, or up to 2 years. Patients underwent pre- and post-treatment biopsy of one irradiated lesion. Results: A total of 35 patients (Seq/Con 19/16) were enrolled and evaluable for toxicity analysis (SBRT and at least 1 cycle N/Ip). Brain metastases were present in 27%. PD-L1 expression: 0% (16), 1-49% (10), &gt;50% (9). Median number of metastases treated with SBRT was 3.2. 6 patients experienced DLT (4 pneumonitis), resulting in dose reduction in central lung Seq cohort of the organs at risk (OAR) by 20%. Median PFS by RECIST (total/Seq/Con) was 5.9 mo, 95% CI: 4.9-13.1/ 6.2 mo, 95% CI: 3.5-12.6/ 5.9 mo, 95% CI: 3.1-18.0. RECIST best response was 11% CR, 57% PR, 6% SD, and 26% PD. Treatment past first progression was allowed, and time to second line therapy (chemotherapy) by arm (Seq/Con) was NR/17.5 months. Median OS has not been reached with median follow up of 15mo. PDL1 status did not impact PFS (p = 0.64) nor OS (p = 0.77). Conclusions: Multisite SBRT and concurrent N/Ip was well tolerated. Responses appear durable as median OS was not reached. Multimodality therapy with mSBRT and dual checkpoint inhibitor therapy resulted in impressive tumor control and clinical benefit with promising efficacy. Clinical trial information: NCT03223155 .
Proton pump inhibitors and risk of hip fracture: a systematic review
Authors: Ying Zhang, Xiaofeng Yu, Gansheng Zhang, Zhengyang Guo, Ziyan Zhang
Journal: BMJ (2015)

Objective
To explore the effects of using proton pump inhibitors (PPIs) on the outcomes of hip fracture.


Methods
Searches were conducted through Medline, Embase, Cochrane Library and Chinese Biomedical Literature Database to identify the studies of the association between PPIs exposure and hip fracture. Quality of studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Pooled odds ratios (ORs) and 95% confidence interval (CIs) were calculated for the risk of hip fracture associated with current exposure of PPIs. And several subgroups were analyzed by dosing duration, dose, osteoporosis and corticosteroid usage to explore potential study heterogeneities. All statistical analyses were performed with STATA software.


Results
Among 11 publications included for final analysis, there were a total of 1 107 577 subjects with an average age of over 60 years. A positive relationship existed between PPIs exposure and hip fracture with an OR of 1.46 (95%CI: 1.26-1.70, P=0.000) as compared with non-PPI-users, especially those on concurrent corticosteroid and PPIs. A significantly increased risk of hip fracture was found in the group of a short-term duration for under 1 year (OR=1.18, 95%CI: 1.01-1.38, P=0.041), medium-term for 1-3 years (OR=1.23, 95%CI: 1.01-1.49, P=0.038) and longer duration for over 6 years (OR=1.38, 95%CI: 1.27-1.50, P=0.000). Furthermore, concurrent use of PPIs was not associated with an increased risk of hip fracture in a definite dose-response manner. As compared with non-PPI-users, no significantly increased risk of hip fracture was found in PPI-users with osteoporosis (P>0.05). Publication bias was not present.


Conclusions
Use of PPIs may be somewhat associated with an increased risk of hip fracture. Considering potential adverse effects, clinicians should prescribe cautiously PPIs for high-risk patients, especially elders.


Key words: 
Fractures, bone; Hip; Proton pump inhibitor; Meta-analysis
Comment on: ‘Metagenome-wide association study of gut microbiome revealed novel aetiology of rheumatoid arthritis in the Japanese population’ by Kishikawa<i>et al</i>
Authors: Kaori Kitamura, Hiroshi Shionoya, Kuniaki Terato, Suguru Suzuki, Richio Fukai, Shinichi Uda, Chiyuki Abe, Hiromitsu Takemori, Keita Nishimura, Hisashi Baba, Takaki Waritani, Kou Katayama
Journal: Annals of the Rheumatic Diseases (2020)

The recent paper from Kishikawa et al 1 provides an extremely important new insight on the concept of oral-gut microbiome axis and rheumatoid arthritis (RA) pathogenesis.

Alterations in the gut microbiome at mucosal sites have been implicated in the pathogenesis of RA.2–4 Increasing evidence suggests a link between RA and periodontal infections caused by Porphyromonas gingivalis (Pg) .5 Oral infection by Pg in an animal model revealed increased serum levels of lipopolysaccharide (LPS), dysbiosis and aggravation of arthritis.6 7 Therefore, the pathogenesis of RA is considered to be associated with the immunomodulatory activity of oral and gut microbiome.8 However, few studies have explored the relationship between the oral-gut microbiome axis and RA pathogenesis.

We previously investigated the relationship between RA disease activity using activity indices and biomarkers; the total bacterial counts and the counts of five well-known gut bacteria species; LPS-related biomarkers and IgG and IgA anti- Pg -LPS antibodies in 87 patients with established RA showing inadequate responses to conventional synthetic disease-modifying antirheumatic drugs or exhibiting severe complications.9 (online supplementary table 1)### Supplementary data

[annrheumdis-2020-217808supp001.pdf]

Little significant relationship was observed between the counts of the total bacteria, five species of bacteria and activity indices and biomarkers.(table 1) The levels of LPS-related biomarkers, particularly serum LPS-binding protein (LBP), were positively correlated with activity indices and biomarkers, suggesting …
Inclisiran Durably Lowers Low-Density Lipoprotein Cholesterol and Proprotein Convertase Subtilisin/Kexin Type 9 Expression in Homozygous Familial Hypercholesterolemia
Authors: G. Kees Hovingh, Norman E. Lepor, David Kallend, Robert M. Stoekenbroek, Peter L.J. Wijngaard, Frederick J. Raal
Journal: Circulation (2020)
PD-1 blockade inhibits osteoclast formation and murine bone cancer pain
Authors: Kaiyuan Wang, Yun Gu, Yihan Liao, Sangsu Bang, Christopher R. Donnelly, Ouyang Chen, Xueshu Tao, Anthony J. Mirando, Matthew J. Hilton, Ru-Rong Ji
Journal: Journal of Clinical Investigation (2020)

Emerging immune therapy, such as with the anti–programmed cell death–1 (anti–PD-1) monoclonal antibody nivolumab, has shown efficacy in tumor suppression. Patients with terminal cancer suffer from cancer pain as a result of bone metastasis and bone destruction, but how PD-1 blockade affects bone cancer pain remains unknown. Here, we report that mice lacking Pdcd1 (Pd1−/−) demonstrated remarkable protection against bone destruction induced by femoral inoculation of Lewis lung cancer cells. Compared with WT mice, Pd1−/− mice exhibited increased baseline pain sensitivity, but the development of bone cancer pain was compromised in Pd1−/− mice. Consistently, these beneficial effects in Pd1−/− mice were recapitulated by repeated i.v. applications of nivolumab in WT mice, even though nivolumab initially increased mechanical and thermal pain. Notably, PD-1 deficiency or nivolumab treatment inhibited osteoclastogenesis without altering tumor burden. PD-L1 and CCL2 are upregulated within the local tumor microenvironment, and PD-L1 promoted RANKL-induced osteoclastogenesis through JNK activation and CCL2 secretion. Bone cancer upregulated CCR2 in primary sensory neurons, and CCR2 antagonism effectively reduced bone cancer pain. Our findings suggest that, despite a transient increase in pain sensitivity following each treatment, anti–PD-1 immunotherapy could produce long-term benefits in preventing bone destruction and alleviating bone cancer pain by suppressing osteoclastogenesis.
Irinotecan and temozolomide upfront and in relapsed Ewing sarcoma: A translational study on MGMT (O6-methylguanine–DNA methyltransferase) and ABCG2 (MGMTLiberati).
Authors: Emanuela Palmerini, Michela Pasello, Robin Lewis Jones, Maria Cristina Manara, Franca Fagioli, Giovanni Grignani, Alessandra Longhi, Marilena Cesari, Massimo Eraldo Abate, Anna Paioli, Elisabetta Setola, Rossella Hakim, Lorenzo D'Ambrosio, Alessandro Parra, Asaftei Dorin Sebastian, Alberto Righi, Luca Morandi, Davide Maria Donati, Stefano Ferrari, Katia Scotlandi
Journal: Journal of Clinical Oncology (2020)

e23564 Background: Activity of temozolomide (TEM) and irinotecan (IRI) in recurrent Ewing sarcoma (EWS) was demonstrated. Few data are available on TEMIRI use upfront. Biological predictive factors are lacking. Methods: This multi-institutional retrospective study (NCT03542097) included 59 patients with EWS. 8 patients with very high risk (HR) EWS (multivisceral ± bone marrow) received TEMIRI (TEM 100 mg/m2/day oral, and IRI 40 mg/m2/day intravenous, days 1-5, every 21 days) upfront, 51 patients after relapse (28% in 1st line, 72% ≥ 2nd line). Overall response rate (ORR: CR+PR), SD, and PD, progression-free (PFS) and overall survival (OS) were assessed. The relationship between pre-treatment expression of MGMT and ABCG2 (when FFPE tissue available) with ORR, PFS and OS was evaluated. Results: Median age was 27 years (range 4-62 years): 47 patients (80%) were adults (≥18 years), 35 (61%) had ECOG 0 and 42 (71%) presented with multivisceral disease (+ bone marrow in 5). MGMT was positive in 16/30 (53%), ABCG2 in 4/33 (12%). ORR for upfront TEMIRI (n = 8) was 50% (CR + PR = 1 + 3), with SD 50%, while in recurrent EWS (n = 49, 2 patients no measurable by RECIST) ORR was 31% (CR + PR = 4 + 11), SD 38%, and PD 31%. A better ORR was observed in adult (p = 0.008) &amp; ECOG 0 (p = 0.001) patients; MGMT &amp; ABCG2 expression did not influence ORR. 6-mos PFS was 87% after TEMIRI upfront, 43% at recurrence (p = 0.06), and 65% vs 28% (p = 0.02) for ECOG 0 vs ECOG 1-2, respectively. 6-mos PFS was 62% in MGMT+ vs 33% in MGMT- (p = 0.4) and 75% in ABCG2+ vs 50% in ABCG2- (p = 0.7). Median time to progression (TTP) with upfront TEMIRI was 9 months (range 5-28 months), with 1 patient with ongoing CR at 56 months; median TTP at relapse was 3 months (1-29 months). MGMT and ABCG2 expression did not influence 1-yr OS, whereas ECOG (0 vs 1-2) did (88% vs 31% p &lt; 0.001). Grade 3-4 diarrhea, neutropenia, and thrombocytopenia incidence was &lt; 5%, 1 patient with recurrent kidney EWS died of acute liver failure. Conclusions: TEMIRI showed promising activity in a very unfavorable cohort of EWS patients, with manageable toxicity. Performance status correlated with 6-month PFS &amp; OS whereas MGMT &amp; ABCG2 did not. Clinical trial information: NCT03542097 .
Endoscopic and clinicopathological characteristics of gastrointestinal schistosomiasis
Authors: Chun-cui Ye, Shi-yun Tan, Xiao-fang Luo, Lei Shen, Zhi-xiang Shen
Journal: BMJ (2013)

The clinical manifestation, endoscopic findings and histopathological characteristics of 162 patients with gastrointestinal schistosomiasis were retrospectively analyzed. Among 162 patients, there were 29 cases of gastric schistosomiasis and 133 cases of intestinal schistosomiasis. The main clinical manifestations included stomachache, diarrhea and mucous bloody stool. Endoscopic findings: in 29 cases of gastric schistosomiasis, 18 were ulcerative type, 5 inflammatory type, 6 proliferative type and 7 cases combined with gastric cancer. In 133 cases of intestinal schistosomiasis, 17 were acute inflammatory type, 81 chronic inflammatory type, 33 mixture inflammatory type and 32 combined with colorectal cancer. Forty nine cases (30.25%) were misdiagnosed for various reasons; commonly misdiagnosed as ulcerative colitis, intestinal tuberculosis, chronic gastritis, and gastrointestinal tumors. There are no specific clinical manifestations or endoscopic findings of gastrointestinal schistosomiasis; epidemiological data, endoscopy combined with multi-site multi-block biopsy may improve the diagnosis.


Key words: 
Schistosomiasis; Endoscope, gastrointestinal
Clinical analysis of elderly patients with osteoporotic hip fractures
Authors: Xi Zheng, Min Zhu
Journal: BMJ (2017)

Clinical data of 448 patients aged ≥60 years with osteoporotic hip fractures admitted in Shanghai Huashan Hospital between January 2010 and December 2014 were retrospectively analyzed. Among 448 cases, there were 143 males and 305 females; 196 cases aged 80-89 years (43.8%) and 137 cases aged 70-79 years (30.6%); 304 cases of femoral neck fracture (67.9%) and 144 cases of intertrochanteric femoral fracture (32.1%); the fractures caused by fall in 328 cases (73.2%) and comorbidity with hypertension and diabetes mellitus in 415 cases (92.6%). Two hundred and sixty eight patients were followed up for 2 years, among whom re-fractures occurred in 17 cases. The study indicates that health education is important for prevention of osteoporotic fractures in elderly people.


Key words: 
Osteoporosis fractures; Hip fracture; Elderly
MSK-ACCESS for noninvasive somatic mutation profiling of lung cancers utilizing circulating tumor DNA.
Authors: Emily S. Lebow, Yonina R. Murciano-Goroff, Angela Rose Brannon, Ahmet Zehir, Maria E. Arcila, Ryma Benayed, Jamie E. Chaft, Alexander E. Drilon, Mark G. Kris, Daniel Richard Gomez, Pedram Razavi, Jorge S. Reis-Filho, David Randolph Jones, Charles M. Rudin, James M. Isbell, David B. Solit, Marc Ladanyi, Dana Tsui, Michael F. Berger, Bob T. Li
Journal: Journal of Clinical Oncology (2020)

3529 Background: Circulating cell-free DNA (cfDNA) next-generation sequencing (NGS) is a promising strategy for non-invasive molecular profiling of cancers. MSK-ACCESS (Analysis of Circulating cfDNA to Evaluate Somatic Status) is a hybridization-capture targeted NGS assay that detects somatic variants in select exons of 129 genes with matched white blood cell sequencing. We present the initial clinical experience with MSK-ACCESS among patients with advanced non-small cell lung cancer (NSCLC). Methods: Patients with stage IV NSCLC underwent prospective MSK-ACCESS testing at initial diagnosis or progression of disease on targeted therapy between June 2019 and January 2020. A subset of patients had matched tissue-based NGS testing with the MSK-IMPACT 468 gene assay. We assessed oncogenic driver detection, turnaround time, plasma-tissue concordance, and matching to therapy. National Comprehensive-Cancer Network designated driver alterations were included in evaluation of tissue-plasma concordance (EGFR, ALK, KRAS, MET, RET, BRAF, HER2, ROS1, NTRK). Turnaround time was compared by a two-sided Wilcoxon signed-rank test. Results: A total of 201 patients with NSCLC had MSK-ACCESS testing at initial diagnosis (n = 79) or following progression of disease (n = 122). The median turn-around-time from plasma collection to MSK-ACCESS report was 16 days (range: 9 – 36 days) compared to 19 days from lab receipt of tissue to report (range: 12 – 57) for MSK-IMPACT (p &lt; 0.001). Among patients with a driver detected on MSK-ACCESS, 100% (92/92) had an identical driver detected on MSK-IMPACT. Among patients with a driver detected on MSK-IMPACT, 75% (92/123) had an identical driver detected on MSK-ACCESS. This rate was similar among patients who were treatment-naive (74%; 64/86) and had disease progression (76%, 28/37) at the time of MSK-ACCESS. MSK-ACCESS identified driver alterations that directly guided first-line targeted therapy (n = 18) with response in all patients with available radiographic follow-up (n = 10), including a patient without confirmatory tissue testing. MSK-ACCESS identified resistance alterations among patients with disease progression including EGFR T790M, EGFR C797S, ROS1 G2032R, as well as a BRAF fusion. Conclusions: MSK-ACCESS successfully identified driver alterations with high concordance to tissue-based testing, directly guided patients to therapy with clinical responses, and detected known and novel resistance mechanisms. This assay warrants further clinical development to guide and facilitate precision oncology.
拉米呋啶治疗乙肝肝硬化停药后病情加重一例
Authors: 代永安, 骆名其, 高士成
Journal: BMJ (2004)

患者男,44岁,工人.1999年11月因乏力、纳差、腹胀,检查肝功能异常,HBsAg、HBcAb、HBeAb阳性诊断为乙型肝炎(CHB)在我院门诊间断行一般护肝、对症治疗.至2000年4月病情逐渐加重,检查提示为乙型肝炎肝硬化(ALC)并脾功能亢进.住院给予保肝、支持、利尿、对症、中西医结合治疗近3个月,腹水水肿消退、黄疸下降、肝功能改善,但总胆红素徘徊于70～80 μmol/L,丙氨酸转氨酶(ALT)60～70 U/L,天冬氨酸转氨酶(AST)70～80 U/L,脾功能亢进无改善。
Use of treatment pathways reduce cost and increase entry into clinical trials in patients (pts) with non-small cell lung cancer (NSCLC).
Authors: James L. Weese, Corey J. Shamah, Federico Augusto Sanchez, Maharaj Singh, Carol Huibregtse, Kevin Clement, Anne Marie Barry-Weers, Amy L. Bock, Dorothy L. Mitchell, Amy Beres
Journal: Journal of Clinical Oncology (2020)

e21000 Background: VIA Oncology evidence-based pathways have been integrated into our medical oncology workflows since November 2014. Within 3 months, compliance was high for our 42 medical oncologists at 19 sites working with a common EHR with over 85% of pts treated on pathway. The aim of this study was to determine if there was a significant difference in the overall cost of treatment between pts treated on pathway versus off pathway, and whether on pathway pts had a lower rate of ED use and unplanned admissions within 30 days of chemotherapy as required in the new CMS directives. Methods: Newly diagnosed NSCLC pts diagnosed between January 1, 2017 to December 31, 2018 were identified from the tumor registry for the system. The VIA database was queried to separate these pts into two groups – those pts who were treated on pathway, and those who were off pathway. In addition, we divided pts into early diagnosis, advanced/curative, and advanced/non-curative. The data warehouse was utilized to determine the total charges of adjuvant medical oncology treatment for these pts. In addition, data was extracted for the same groups to determine those pts who sought ED evaluation and or hospital admission within 30 days of chemotherapy treatment (CMS-35). Statistical analysis was performed using Chi-square/Fisher’s exact test to compare proportions and t-test for independent samples to compare treatment costs and ED/hospitalizations between the on and off pathway groups. Results: During the 2 years, 407 (81.4%) NSCLC pts were treated on pathway (including clinical trials); 93 (18.6%) were off pathway. All patients undergoing treatment were ECOG 0-2 Performance Status. Mean cost for treating the on-pathway group was $104,436 compared to $183,717 for the off-pathway pts (p = 0.01). Since implementing pathways, clinical trial entry rose from 27 to 66/yr. 25.8% of on pathway compared to 29% of off pathway fell into the CMS 35 group. Conclusions: Standardized usage of evidence-based pathways can be used successfully across a large number of providers over wide geography. Adherence to pathways results in significant cost savings for each patient and significant rise in clinical trial entry.