tbuckley/cabot-search huggingface dataset:
Did Reduced Alveolar Delivery of Surfactant Contribute to Negative Results in Adults with Acute Respiratory Distress Syndrome?
Authors: James B. Grotberg, Marcel Filoche, Douglas F. Willson, Krishnan Raghavendran, Robert H. Notter
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

conditions, bringing monitoring of regional ventilation a step closer.EIT was also capable of visualizing a more accurate regional redistribution of ventilation using a multiplane and optimized chest shape approach.
What’s in the ‘special sauce’ of protocol-driven outpatient palliative care consultations?
Authors: Gulcan Bagcivan, Marie Bakitas, J Nicholas Dionne-Odom, Jennifer Frost, Margaret Plunkett, Lisa A Lisa A Stephens, Peggy Bishop
Journal: Journal of Clinical Oncology (2016)

139 Background: Initial outpatient palliative care consultations (OPCC) in clinics are usually requested for uncontrolled symptoms. The purpose of this substudy was to determine the nature of recommendations made in early PC (EPC) protocol-driven OPCC. Methods: Using a standardized tool, we conducted a content analysis on the assessment and plan components of protocol-driven OPCCs. OPCCs were conducted as a component of the ENABLE [Educate, Nurture, Advise, Before Life Ends] RCT (10/2010-9/2013) consisting of an OPCC and 6 structured weekly telephone coaching sessions and monthly follow up either at study entry (early) or 12 weeks later (delayed). We coded OPCCS for 37 specific recommendations, grouped into 3 categories: general, symptom-specific or advance care planning (ACP). Results: Of 207 study participants, 142 (early = 71; delayed=71) had an OPCC; 65 (31%) did not receive OPCC due to unable (n=35), unknown (n=17), and declined (n = 13). OPCC patients were mostly female (51%), married or living with partner (65%), rural-dwelling (66%), high school graduates (54%), white (99%), Catholic (30%), retired (46%), and had GI cancers (44%). Patients who had OPCCs had statistically ↓ CAGE (p = 0.03), ↑rural-dwelling (p = 0.03), and ↓hospice referral (p = 0.03) at baseline. Median OPCC length was 60 minutes (range 15-105). The most frequent general recommendations were for counselling (34%, n = 48) and medication review (30%, n = 43); symptom-specific recommendations were for pain (16%, n = 23), depression (11%, n = 16), and constipation (8%, n = 11); and ACP were for AD completion (20%, n = 29), identifying surrogate (18%, n = 25), and discussion of illness trajectory (17%, n = 24). There were no significant differences in recommendations between early and delayed group (p &gt; 0.05) except hospice discussion was ↑ in delayed patients (p = 0.02). Conclusions: Protocol driven OPCCs for newly diagnosed advanced cancer patients can prospectively address patients’ needs for additional counseling, symptom control and ACP. Future analyses will focus on relationships regarding overall EPC ‘dose’ and longitudinal patient outcomes.
A phase II study of twice-daily (BID) cytarabine (A) and fludarabine (F) and gentuzumab ozogamycin (GO) in patients (pts) with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS).
Authors: H. Ghanem, H. Kantarjian, G. Garcia-Manero, F. Ravandi, S. Faderl, J. E. Cortes, A. Reyes, S. M. O'Brien, G. Borthakur, T. M. Kadia, J. A. Burger, M. Konopleva, E. Jabbour
Journal: Journal of Clinical Oncology (2011)

6568 Background: High-dose A containing regimens are still considered standard options for pts with AML relapsing after a first Complete Remission (CR) lasting more than 12 months. We conducted a phase II study assessing the efficacy and safety of BID FA-GO. Methods: Pts with Relapsed/Refractory AML, de novo AML unfit for other medical therapies, intermediate-2 and high-risk MDS, and CML-BC, with a PS < 3, as well as normal organ functions were eligible. Pts were scheduled to receive F 15 mg/m2 IV q12 hrs day 1 to 5 as well as A at the dose of 0.5 g/m2 IV over 2 hrs q12 hrs day 1 to 5. GO was administered at the dose of 3 mg/m2 IV on day 1 for the 1st 66 pts enrolled. Courses were repeated every 4 to 6 weeks for a maximum of 7 courses. Pts with CML were allowed to receive concomitant TKIs. Results: 103 evaluable pts were enrolled: 13 (14%) with de novo AML, 10 (10%) with AML in 1st relapse with a duration of 1st CR (CRD1) of ≥12 months, 25 (26%) with AML with CRD1 <12 months, 48 (50%) with AML in 2nd relapse and beyond, 4 (4%) with MDS, and 8 (8%) with CML-BC. Median age was 62 years; 84 pts (88%) had a PS ≥1. Cytogenetic analyses were abnormal in 68 % including chromosomes 5 and 7 abnormalities in 20%. The overall response (OR) rate was 32% including CR in 25 pts (26%) and CRp in 6 (6%). The overall 4-week mortality rate was 9% (Table). With a median follow-up of 16 weeks, the 16-week EFS, OS, and CRD rates were 30%, 59%, and 88%, respectively. When compared to historical match cohort pts treated at our institution, BID FA-GO was better, with an ORR rate of 60 % in pts with AML in first relapse with CRD1 ≥12 months compared to an expected rate of 50%, 28% in pts with relapsed AML with CRD1< 12 months compared to 11%, and 23% in pts with AML beyond the first salvage compared to 7%. The treatment was well tolerated with only 3% of the pts experiencing grade 3 and 4 toxicities including mainly skin rash. Conclusions: BID FA-GO appears to be active with an ORR of 32% in heavily pre-treated population. This combination appears to be safe with a low rate of 4-week-mortality of 9%. Parameter (%) De novo S1 (CRD1 ≥ 12 mos) S1 (CRD1 < 12 mos) ≥ S2 OR 53 60 28 23 CR 38 50 28 17 CRP 15 10 0 6 4-wk mortality 8 0 12 10
Population-based impact on overall survival (OS) after the introduction of docetaxel as standard therapy for metastatic castration resistant prostate cancer (CRPC).
Authors: Robert Richard Zielinski, Scott Tyldesley, Kim N. Chi
Journal: Journal of Clinical Oncology (2013)

77 Background: Docetaxel (DOC) was the first systemic therapy to improve OS (Hazard Ratio (HR) = 0.79) for patients (pts) with CRPC and a standard therapy since 2004. Because of the potential for severe toxicity with DOC, its use has been subject to pt selection. Even with this selective use, we sought to determine whether the introduction of docetaxel has improved OS at a population level. Methods: We performed aretrospective review of all CRPC pts treated with palliative radiotherapy (PRT) to bone metastases in the province of British Columbia, Canada. The pre-docetaxel cohort (pre-D) received PRT from 1998-2001. The docetaxel-era cohort (post-D)received PRT from 2006-2009. Time of first PRT to bone was used to select pts at a similar point in their disease state (i.e., onset of bone pain). Mortality and cause of death was attained from public registries. OS was calculated from time of first PRT using the Kaplan-Meier method and compared using the log-rank test. Results: Comparative baseline characteristics for the 1876 patients split into the pre-D (n=919) and post-D (n=957) eras were: metastatic at diagnosis 30% vs. 33% (p = 0.09), median age at PRT 75.5 vs. 76.7 years (p=0.04), time from diagnosis to PRT 3.9 vs. 3.1 years (p = 0.31), received DOC 7% vs. 37% (p &lt; 0.0001). Median OS from time of first PRT was 7.5 months (m) vs. 10.3 m (HR: 0.79, 95% Confidence Interval 0.70 – 0.89, p &lt; 0.0001) in the pre-D and post-D cohorts respectively. Within the post-D cohort, the median OS from time of RT was longer in pts receiving DOC at 13.9 m vs. 7.4 m for pts not receiving DOC (p=0.004). Conclusions: In this population based analysis, the introduction of DOC as a standard of care was associated with a significant improvement in OS even though DOC penetrance was &lt;50%. This demonstrates for the first time the generalizability of the TAX-327 study results to the population at large. Even as the therapeutic landscape for CRPC evolves with the introduction of new agents that improve OS with favourable toxicity profiles, these data support the continued use of DOC in appropriately selected patients.
Prognostic utility of CCP score in men with prostate cancer after primary external beam radiation therapy.
Authors: Stephen J. Freedland, Leah Gerber, Julia E. Reid, William Welbourn, Eliso Tikishvili, Jimmy Park, Adib Younus, Alexander Gutin, Zaina Sangale, Jerry S. Lanchbury, Joseph Kamel Salama, Steven Stone
Journal: Journal of Clinical Oncology (2013)

47 Background: Accurate risk stratification improves decision making in localized prostate cancer. The CCP score, a prognostic RNA signature based on the average expression level of 31 cell cycle progression (CCP) genes, was developed to aid in this task. Previously, the CCP score was shown to be predictive of biochemical recurrence (BCR) after prostatectomy, and prostate cancer specific mortality in men undergoing observation. However, the value of CCP score in men undergoing primary electron beam radiation therapy (EBRT) was untested. Methods: The CCP score was derived retrospectively from the diagnostic biopsy of 141 patients treated with EBRT at the Durham VA medical Center. Inclusion criteria were disease diagnosis from 1991 to 2006 and available biopsy tissue. Approximately half of the cohort was African-American. Outcome was time from EBRT to BCR using Phoenix definition, and median follow-up for patients without BCR was 4.8 years. Association with outcome was evaluated by CoxPH survival analysis and likelihood ratio tests. Results: Patient data were censored at 5-years of follow-up and 19 patients (13%) had BCR. The median CCP score was 0.12(IQR -0.43 to 0.66). In univariable analysis, CCP score was a significant prognostic variable (p-value = 0.0017). The hazard ratio (HR) for BCR was 2.55 (95% CI (1.43, 4.55)) for a one-unit increase in CCP score (equivalent to a doubling of gene expression). In a predefined multivariable analysis that included Gleason score, PSA, and percent positive cores, the HR for CCP changed only marginally and remained significant (HR per CCP unit 2.09 (95% CI (1.05, 4.18), p-value = 0.035), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. Further adjustment for hormonal therapy or radiation dose did not materially alter this association. The score was also associated with prostate cancer specific mortality. There was no evidence for interaction between CCP and any clinical variable, including ethnicity. Conclusions: In a cohort of men treated with EBRT, the CCP score was significantly associated with outcome and provided prognostic information beyond what was available from clinical parameters. If validated in a larger cohort, CCP score could be used to select high-risk men undergoing EBRT who may need combination therapy for their clinically localized prostate cancer.
Use of methylation profiling to identify predictive markers in gastric cancer for respond to 5-fluorouracil (5FU)-based chemotherapy.
Authors: N. Liem, P. Lim, M. Loh, A. Vaithilingham, R. C. Soong, W. Yong
Journal: Journal of Clinical Oncology (2010)

e14546 Background: Fluoropyrimidine based adjuvant therapy has been demonstrated to improve outcome of patients with early gastric cancer. Hypermethylation of selected genes have been reported to have prognostic relevance in 5FU-based chemotherapy in colorectal cancer but no studies have been reported in gastric cancer. In this study we evaluate the utility of cancer DNA methylation status as predictive markers for 5FU therapy. Methods: 5FU was treated in 43 gastric cell lines to obtain their IC50. To investigate methylation markers relevant to 5FU response, methylation array profiling of these cell lines were carried out and segregated to the three most sensitive and resistant cell lines based on their 5FU IC50 values. Methylation profiling of 60 gastric tumours from patients who had received adjuvant 5FU was also carried out. Results: Sensitive cell lines had IC50 below 1.5 μM, compared to resistant cell lines with IC50 values of > 100 μM. Methylation profiling of gastric cell lines revealed 135 CpG loci that were differentially methylated between resistant and sensitive groups. 5FU sensitive cell lines had 127 CpG loci that were heavily methylated compared to 5FU resistant cell lines, suggesting that hypomethylation may play a role in the resistance to 5FU in vitro. By coupling the methylation markers of 28 genes from the in vitro sensitivity assay with the clinical samples, we found that patients with a high methylation score have significantly better survival. Furthermore 13/28 of the identified selected methylated genes were found also found to to be associated with proliferation, apoptosis and kinase. Conclusions: We have identified methylation markers that were predictive of patient outcome to 5FU therapy. These markers may have potential applications for individualized 5FU therapy in patients with gastric cancer. No significant financial relationships to disclose.
Analysis of Kohne's prognostic index in <i>KRAS</i> wild-type patients with metastatic colorectal cancer (mCRC) treated with salvage-line cetuximab-based regimen: HGCSG0901.
Authors: Ayako Doi, Satoshi Yuki, Yasushi Tsuji, Takahide Sasaki, Hiraku Fukushima, Kazuteru Hatanaka, Hirohito Naruse, Hiroyuki Okuda, Takaya Kusumi, Koshi Fujikawa, Yasuo Takahashi, Soh Saitoh, Shinya Kajiura, Ayumu Hosokawa, Yutaka Watanabe, Fumiyasu Yamamoto, Mineo Kudo, Nobuaki Akakura, Yuh Sakata, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2014)

634 Background: In the treatment for mCRC, it is essential for understanding the prognosis of each individual patient. Köhne’s index (KI) based on performance status, white blood cell count, alkaline phosphatase and number of metastatic sites has been previously proposed. However, in the salvage setting, the validity of KI has not been reported in patients treated by cetuximab-based chemotherapy. Methods: 269 patients with mCRC treated by cetuximab contained chemotherapy were retrospectively registered from 27 centers in Japan. This analysis was included in the KRAS wild-type patients who were refractory to or intolerant for 5-FU/irinotecan/oxaliplatin and were never administered anti-EGFR-antibody. Univariate and multivariate analysis for overall survival were performed using patient characteristics. Survival analyses were performed with Kaplan-Meier method, log-rank test and Cox proportional hazards model. The analysis was also designed to determine whether the Köhne’s classification could be extended to other endpoints such as progression-free survival. Results: All data were available for prognostic categorization in 127 patients. Median overall and progression-free survival was 9.8 and 4.2 months. The distribution and median survival / progression-free survival for KI were as follows: low risk (L) (n = 40; 13.1/5.1 months), intermediate risk (I) (n = 17; 9.6/3.5 months), and high risk (H) (n = 70; 7.6/4.1 months). For overall survival, there was significant difference between L and H (p = 0.004), but not between L and I (p = 0.213), and between I and H (p = 0.321). For progression-free survival, there was tended to difference between L and H (p = 0.083), but not between L and I (p = 0.392), and between I and H (p = 0.630). In Cox multivariate analysis, KI showed an independent prognostic impact (HR 1.370, p = 0.010), but not predictive impact (HR 1.147, p = 0.212). Conclusions: In this analysis, KI might be a prognostic factor in salvage treatment with cetuximab-based regimen, but no effect predicted impact. Moreover, the prospective evaluation is needed for the further validation.
Trastuzumab emtansine (T-DM1) in previously treated HER2-positive metastatic breast cancer (MBC): Results from an expanded access study.
Authors: Denise Aysel Yardley, Ian E. Krop, Patricia LoRusso, Nicholas J. Robert, Musa Mayer, Oyewale O. Abidoye, Catherine Lai, Bongin Yoo, Edith A. Perez
Journal: Journal of Clinical Oncology (2013)

166 Background: T-DM1 is an antibody-drug conjugate composed of trastuzumab, a stable linker, and the cytotoxic agent DM1. Few T-DM1 data are available in settings approximating clinical practice. We present safety and efficacy data from T-PAS, an expanded access study of T-DM1 in patients (pts) with previously treated HER2-positive MBC. Methods: T-PAS is a US multicenter study of T-DM1 (3.6 mg/kg q3w) in HER2-positive (IHC 3+ or FISH/CISH+) locally advanced or MBC. Key eligibility criteria: prior anthracycline and taxane; prior capecitabine or 5-FU and ≥2 HER2-directed agents (including trastuzumab and lapatinib) for MBC; LVEF ≥50%. Primary endpoint: safety; secondary endpoint: investigator-assessed objective response rate (ORR) in pts with measurable disease. Safety was assessed on day 1 of each cycle; ECHO/MUGA scans were every 12 weeks. Results: This analysis includes 215 pts enrolled in May 2010–Sep 2011 (data cutoff 7/31/2012). Pts received a median of 7 prior systemic MBC therapies (range 1–23) with a median cumulative anthracycline dose of 240 mg/m 2 (range 6–2645). At baseline, median LVEF was 60% and 50% of pts had investigator-reported cardiovascular disease. Median follow-up was 5.9 months (range 0.1–25.3); median T-DM1 duration was 5.0 months (range 0–23) with 15.8% receiving &gt;18 cycles. ORR was 25.6% (42/164). Rate of grade ≥3 AEs was 43.7% and of SAEs of any grade was 18.1%. Most common all-grade AEs were fatigue (50.7%), nausea (36.3%), and headache (24.2%). Most common grade ≥3 AEs were thrombocytopenia (7.9%), fatigue (4.7%), and increased aspartate aminotransferase and anemia (each 3.7%). There were no grade ≥3 bleeding events. Cardiac dysfunction (primarily asymptomatic decreases in LVEF) was reported in 8 pts (3.7%); 4 were grade ≥3, 3 resulting in T-DM1 discontinuation. Conclusions: In this study that more closely reflects the real-world setting, the safety profile of T-DM1 was similar to that previously reported in conventional clinical trials, with no new safety signals. In this pretreated population (median of 7 prior therapies for HER2-positive MBC), significant activity was observed. Clinical trial information: NCT01120561.
Phase III study in stage IV non-small-cell lung cancer (NSCLC) patients (pts) treated with two cycles of cisplatin/gemcitabine followed by a randomization to three additional cycles of the same combination or gemcitabine alone
Authors: S. Novello, P. Bruzzi, C. Barone, A. Masotti, R. Buosi, G. Michetti, M. Fioretti, S. Barbera, G. Selvaggi, G. V. Scagliotti
Journal: Journal of Clinical Oncology (2005)

7051 Background: Previously (Novello et al. Proc. ASCO 2004 abstr 7069) the preliminary results of this study were reported. Briefly, in a multi-center, phase III study pts with chemonaive, stage IV NSCLC, performance status 0–2, weight loss < 5% and measurable disease after two cycles of cisplatin (75 mg/m2 d2) plus gemcitabine (1250 mg/m2 d1,8) (CG) Q21 days, were randomized (in case of CR, PR or SD) to receive three additional courses of the same combination (arm A) or gemcitabine alone at the same dose and schedule (arm B). Primary objective was the non-inferiority of arm B in terms of 1-year and median survival time using an hazard ratio of 0.75. Results: We enrolled 340 pts and 250 (73%) were randomized. Median age was 62 years, 78% male, PS 0/1 94%, adenocarcinoma 54%, 13% with asymptomatic brain mts. After 2 courses of GC, response rate was: 1% CR,28% PR, 47% SD, 17% PD and 7% NE. Among randomised patients response rate at cycle 5 was: arm A 1%/53%/43%/3%; arm B 2%/35%/60%/3%. Among non-randomised pts median survival time was 4.9 months, while corresponding values in overall population, arm A and arm B were 11.7,15.6 and 13.5 months (arm A vs B, p=0.87, log-rank test). Time to progressive disease was 1.5 months in non randomised patients, 5.8 in all patients and 6.6 and 7.4 in arm A and B, respectively. Overall 1-year survival rate in non randomised pts was 17%, all pts 42%, arm A 54% and arm B 50%. As December 2004, 221 pts (35% censored) died and 295 progressed (13% censored). Toxicity profile favoured arm B in terms of hematological as well non-hematological toxicity. Conclusions: The mature data of this study confirm the non inferiority of arm B which, in consideration of the limited impact on survival of currently available chemotherapy, could be considered a reasonable alternative for the treatment of stage IV NSCLC. No significant financial relationships to disclose.
Oral treatment with uracil-tegafur, etoposide and leucovorin in non-Asian patients with recurrent non-small cell lung cancer: A non-randomized, phase II study
Authors: V. F. Surmont, J. Aerts, E. Pouw, R. M. Vernhout, E. J. Gras, K. Y. Tan, H. Hoogsteden, R. van Klaveren
Journal: Journal of Clinical Oncology (2008)

19019 Background: Maintenance of good quality of life is a very important aspect in the treatment of patients with recurrent advanced NSCLC. Therefore, out-patient treatment regimens with few side-effects are appealing. Purpose of our study was to investigate the activity and toxicity of oral etoposide, UFT and leucovorin in second or third line for non-Asian patients with advanced NSCLC. Methods: Patients with stage IIIB or IV NSCLC treated with one or two prior chemotherapy regimens were eligible. Patients were treated in a non-randomised phase II study with oral etoposide 50 mg/m2/d, Uracil-Tegafur 250 mg/m2/d and leucovorin 90 mg/d (fixed dose) in a 21 day cycle: 14 days treatment followed by 7 days of rest. Treatment was continued until PD. Primary endpoint was RR, secondary endpoints were toxicity and TTP. Minimum RR below which treatment is of no interest was set at 5%. The 2-phase Simon design was used. Results: Of the 35 patients entered in the study (mean age 60.4 yrs, range 42- 79.4 yrs) 25 were evaluable for response: 5 had PD, 17 SD and 3 PR (ORR 9%). Grade 3/4 neutropenia and thrombocytopenia occurred in 11% and 14%, respectively. No febrile neutropenia was observed. Grade 3 non-hematological toxicity included elevated transaminases (2/35), lethargy (5/35), diarrhea (1/35) and nausea (1/35). One patient developed treatment related peripheral arterial ischemia. For all participants the median TTP was 85 days (range 5–723days), for patients treated in 2nd line (18/35) 121 days (range 26–349), whereas for 3rd line patients (17/35) it was 91.5 days (range 5–723). Conclusions: The present study is the first to demonstrate activity of UFT combined with etoposide in 2nd or 3rd line treatment for advanced NSCLC in a non-Asian population. The TTP is comparable with other 2nd or 3rd line treatments, the combination is well tolerated and toxicity is mild. Randomized studies comparing the cost-effectiveness of UFT-etoposide with one of the other registered 2nd or 3rd line treatment are warranted. No significant financial relationships to disclose.