tbuckley/cabot-search huggingface dataset:
Continued gefitinib treatment after disease stabilization prolongs survival of patients with advanced non-small-cell lung cancer
Authors: K. Hotta, K. Matsuo, H. Ueoka, K. Kiura, M. Tabata, S. Harita, K. Gemba, T. Yonei, A. Bessho, M. Tanimoto
Journal: Journal of Clinical Oncology (2005)

7088 Background: This study aimed to investigate the survival outcome of patients with NSCLC who had obtained disease stabilization (SD) with gefitinib treatment and to clarify the effect of continued treatment with gefitinib on prognosis. Methods: We reviewed the clinical records of 365 NSCLC patients who received gefitinib (250 mg/day) in 12 hospitals between 2000 and 2003. Survival was assessed using a landmark analysis and the impact of continued gefitinib treatment on survival was evaluated by considering gefitinib as a time-dependent covariate. Results: In total, 324 (89%) patients (male/female: 67/33%, Ad/others: 74/26%, median age: 67, and ECOG PS 0–1/2–4: 65/35%) were eligible for response analysis. SD occurred in 147 (45%) patients, whereas 71 (22%) patients achieved an objective response. Overall survival (OS) was significantly longer for patients with SD than for those with PD (median OS: 12.1 vs 4.4 months; p<0.0001 by a logrank-test). Gefitinib treatment was discontinued in 54/147 (37%) patients who had SD before disease progression, mainly due to gefitinib-related toxicities including interstitial lung disease(8), infection(7), skin rash(6), nausea/vomiting(4) and hepatotoxicity(3). OS and PFS were longer in those continuing gefitinib treatment compared with those who discontinued treatment (1-year OS: 52.1% vs 36.6%, p=0.08; 1-year PFS: 31.8% vs 5.2%, p=0.0001). Multivariate analysis showed that discontinuation of gefitinib treatment after disease stabilization had a significant impact on progression-free survival in patients with SD (hazard ratio: 1.66, 95%CI=1.07–2.56, p=0.022). Conclusions: Our findings indicate the importance of achieving SD with gefitinib and suggest that continuing gefitinib treatment after SD may prolong progression-free survival. Further studies are required to confirm this effect. No significant financial relationships to disclose.
Phase I/II Trial of Lenalidomide and High-Dose Melphalan with Autologous Stem Cell Transplantation for Relapsed Myeloma: Updated Results
Authors: Nina Shah, Peter F Thall, Denái R. Milton, Qaiser Bashir, Simrit Parmar, Pei Lin, Partow Kebriaei, Yago Nieto, Uday R. Popat, Chitra Hosing, Amanda Cornelison, Ruby Delgado, Elizabeth J. Shpall, Robert Z. Orlowski, Richard E. Champlin, Muzaffar Qazilbash
Journal: Blood (2016)
Phase II trial of temsirolimus (TEM) plus sorafenib (SOR) in hepatocellular carcinoma (HCC).
Authors: Robin Kate Kelley, Halla Sayed Nimeiri, John Dozier Gordan, Jimmy Hwang, Ryan M. McWhirter, Advaita Kanakamedala, Chloe Evelyn Atreya, Laura Kulik, Sheetal Kircher, Mary Frances Mulcahy, Al Bowen Benson, Alan P. Venook
Journal: Journal of Clinical Oncology (2015)

TPS501 Background: The multikinase inhibitor SOR prolongs survival in patients with HCC not amenable to curative therapies. In HCC preclinical models, the combination of SOR with an inhibitor of the mammalian target of rapamycin (mTOR) pathway is synergistic, though single-agent mTOR inhibition did not improve survival in HCC patients after failure of SOR in a phase III trial. We previously completed a phase I study of the mTOR inhibitor TEM combined with SOR in 25 HCC patients which identified the maximum tolerated dose as TEM 10 mg IV weekly and SOR 200 mg PO BID. This two-center, phase II study was developed to examine the efficacy of the combination and to explore candidate biomarkers. The study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support, with activation October 2012. Methods: The study is registered on ClinicalTrials.gov (NCT01687673). Design: Single-arm, one stage phase II trial. Primary endpoint: Time to progression (TTP) by RECIST 1.1. Other endpoints: Progression-free survival, response rate, overall survival, proportion with alpha fetoprotein decline ≥ 50%, toxicity, hepatitis B virus reactivation rate, and exploratory biomarkers including mTOR pathway protein expression in tumor, circulating tumor cells, and blood and tumor micro-RNA profiles. Sample size: 25 evaluable patients are required to detect a difference between the null hypothesis of median TTP &lt; 3 months versus alternate hypothesis of median TTP ≥ 6 months (a clinically-meaningful outcome in advanced HCC), with 1-sided significance level of 10% and power 88% under the exact test. Main eligibility criteria: HCC not amenable to curative therapies, histologically-confirmed, ≥ 1 untreated, radiographically-measurable site of disease. No prior systemic therapy. ECOG ≤ 1. Child-Pugh score ≤ 7 with bilirubin ≤ 2 mg/dL. Treatment and procedures: TEM 10 mg IVweekly plus SOR 200 mg PO BID in 28-day cycles, with collection of archival tumor samples and blood samples at baseline, on treatment, and at progression. Accrual:Sixteen of 25 planned evaluable patients have enrolled. An interim analysis for safety after 30% enrollment met pre-specified target to continue. Clinical trial information: NCT01687673.
Cisplatin-associated nephrotoxicity in clinical trials using serum creatinine (SCr) versus calculated glomerular filtration rate (GFR) as inclusion criterion: A meta-analysis.
Authors: Arati Dahal, Brandon Kyle Bellows, Guru Sonpavde, Matt D. Galsky, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2013)

272 Background: Treatment with cisplatin (CIS) is associated with increased risk of nephrotoxicity and SCr is commonly used to screen patients for renal dysfunction prior to enrollment in trials using CIS. However, GFR is known to better estimate renal function than SCr. The objective of this trial-level meta-analysis was to indirectly compare incidence of WHO grade ≥3 nephrotoxicity associated with CIS therapy when renal function was assessed using SCr vs. calculated GFR during screening for these trials. Methods: A PubMed literature search was used to identify randomized trials comparing treatment regimens including CIS to those without CIS. Studies were included if they were performed between 1990 and 2005, reported SCr or GFR as inclusion criteria, and reported WHO grade ≥3 nephrotoxic events for both the CIS and non-CIS treatment arms. Studies were excluded if they were review articles, observational, phase 1, non-randomized, did not have a comparator group, or were not reported in English. Inverse variance weighted fixed effects (FE) and random effects (RE) methods were used to estimate the relative risk (RR) associated with CIS vs. non-CIS containing regimens with sub-group analyses of studies using SCr, GFR, and either SCr or GFR for screening. Results: The literature search identified 2359 studies. After exclusion criteria, 549 were reviewed and 24 studies (N=5524 patients) met all inclusion criteria for analysis. Of these, 16 studies used SCr (N=3955), 3 used GFR (N=692), and 5 used SCr or GFR (N=877) for screening. Overall incidence proportion of nephrotoxicity was higher for CIS vs. non-CIS regimens (2.1% vs. 0.7%). Overall RR for CIS vs. non-CIS regimens was 2.49 (95%CI 1.37-4.51, p=0.003). In sub-group analyses, the RR was 2.63 (95%CI 1.29-5.39, p=0.008) for SCr compared to 2.39 (95%CI 0.53-10.64, p=0.26) for GFR and 2.03 (95%CI 0.46-9.02, p=0.35) for either SCr or GFR. The RRs did not differ between the FE and RE methods. Conclusions: This indirect comparison meta-analysis shows CIS is associated with a higher likelihood of nephrotoxicity vs. non-CIS regimens, and may be higher when SCr is used instead of GFR as eligibility criteria.
Optogenetic manipulation of anatomical re-entry by light-guided generation of a reversible local conduction block
Authors: Masaya Watanabe, Iolanda Feola, Rupamanjari Majumder, Wanchana Jangsangthong, Alexander S. Teplenin, Dirk L. Ypey, Martin J. Schalij, Katja Zeppenfeld, Antoine A. F. de Vries, Daniël A. Pijnappels
Journal: Cardiovascular Research (2017)

AimsAnatomical re-entry is an important mechanism of ventricular tachycardia, characterized by circular electrical propagation in a fixed pathway. It's current investigative and therapeutic approaches are non-biological, rather unspecific (drugs), traumatizing (electrical shocks), or irreversible (ablation). Optogenetics is a new biological technique that allows reversible modulation of electrical function with unmatched spatiotemporal precision using light-gated ion channels. We therefore investigated optogenetic manipulation of anatomical re-entry in ventricular cardiac tissue.
Methylation of MGMT in paired primary and recurrent GBMs.
Authors: Li Bie, Feng Xian Zhang
Journal: Journal of Clinical Oncology (2012)

65 Background: Epigenetic sliencing of the MGMT gene promoter in primary glioblastomas of patients subsequently treated with TMZ is associated with prolonged survival. Further, several studies have observed a change in MGMT silencing in paired primary and recurrent glioblastoma. However, the relationship between this “MGMT switch” and patients outcome is largely unknown. Methods: The study involved primary and recurrent tumor tissue samples from 53 glioblastoma patients diagnosed and treated within the First Hospital of Jilin University from January 2003 to November 2010. After surgical treatment, all patients were subjected to radiotherapy with concomitant administration of TMZ. Patients that experienced recurrent tumors received TMZ. 53 patients underwent 58 further operations after recurrence (5 pats received a third surgery). MGMT promoter methylation levels were determined using qMSP. The relationship between “MGMT switch” and clinical outcome was investigated. Results: 53 (M/F=33/20; median age: 49.2±3.6, 19.5-72.3 ys) underwent a first operation for GBM. qMSP analysis revealed MGMT promoter methylation in 19 pats (35.8%, A, OS 31.5 ms); no methylation in 34 pats (64.2%, B, OS 7.9 ms). In the recurrent tumors, MGMT promoter methylation was detected in 25 pats (47.2%); and no methylation in 28 pats (52.8%). Comparison of individual pairs of primary and recurrent GBMs revealed a changed methylation status in 10 (18.9%), including 8 changed from unmethylated to methylated tumors (15.1%, C, OS 29.4 ms), 2 changed from methylated to unmethylated tumors (3.8%, D, OS 10.5 ms). Median overall survival (OS) was 12.1 months. MGMT promoter methylation was significantly associated with a favorable clinical outcome (A vs B, p=0.0027). The outcome of patients were not significant different between group A and group C (p&gt;0.01). Conclusions: The methylation status of the MGMT promoter was altered in 10 (18.9%) of 53 recurrent GBM after chemoradiotherapy. 8 patients the promoter changed from unmethylated to methylated and these patients had a median overall survival similar to the better prognosis of patients who had a methylated promoter in their primary tumor. 2 pats where a change from methylated to unmethylated was observed had a poorer outcome.
Prognostic factors and survival of patients with brain metastasis (BM) from breast cancer (BC) who underwent craniotomy.
Authors: Jose Pablo Leone, Diana E. Cunningham, Adrian Lee, Rohit Bhargava, Ronald L. Hamilton, Erik Wiener, Hideho Okada, Adam Brufsky
Journal: Journal of Clinical Oncology (2013)

e22017 Background: BC is the second most frequent cause of BM after lung cancer, with metastases occurring in 10-16% of all patients. BM in patients with BC is a catastrophic event that results in poor prognosis. Identification of prognostic factors associated with breast cancer brain metastases (BCBM) could help to identify patients at risk. The aim of this study was to assess clinical characteristics, prognostic factors and survival of patients with BCBM who had craniotomy and resection in a series of patients treated with modern multimodality therapy. Methods: We analyzed 42 patients with BCBM who underwent resection. Patients were diagnosed with BC between April 1994 and May 2010. Cox proportional hazards regression was selected to describe factors associated with time to BM, survival from the date of first recurrence, and overall survival (OS). Results: Median age was 51 years (range 24-74). Median follow-up was 4.2 years (range 0.6-18.5). The mean time to BM from primary diagnosis was 49 months (range 0-206.22). Patients had a median of 2 BM with a median size of 3.25 cm. The proportion of the biological subtypes of BC was ER+/HER2- 25%, ER+/HER2+ 15%, ER-/HER2+ 30% and ER-/HER2- 30%. Brain radiotherapy was given to 28 patients, of which 10 had stereotactic radiosurgery, 7 whole brain radiation, and 11 both. Median OS from the date of primary diagnosis was 5.74 years. Median survival after diagnosis of BM was 1.33 years. In multivariate Cox regression analyses, stage was the only factor associated with shorter time to the development of BM (P=0.059), whereas age was the only factor associated with survival from the date of recurrence (P=0.027) and with OS (P=0.037). Controlling for age and stage, neither the biological subtype of cancer, the radiation modality nor the site of first recurrence showed any impact on survival. Conclusions: Stage at primary diagnosis correlated with shorter time to the development of BM, while age at diagnosis was associated with shorter survival in BCBM. None of the other clinical factors had influence on survival.
Impact of opioid use on survival in patients with newly diagnosed stage IV non-hematologic malignancies.
Authors: Dylan Michael Zylla, Sara Richter, Alice C. Shapiro, Pankaj Gupta
Journal: Journal of Clinical Oncology (2015)

188 Background: Pain is a challenging problem in patients with advanced cancers. Opioids are commonly required to treat cancer-related pain, but may be associated with tumor progression and shorter survival. We recently reported that high opioid use during the first 90 days after diagnosis is associated with shorter survival in patients with advanced lung cancer. Methods: We identified 1386 newly diagnosed stage IV non-hematologic malignancies from 2005-2013 and gathered pain and opioid utilization within 90 days of treatment using data from electronic medical records and the tumor registry. Opioid utilization was stratified into low opioid exposure (LOE; no opioid prescriptions or one prescription for a short-acting opioid) and high opioid exposure (HOE; any long-acting opioid prescription or 2 or more short-acting opioid prescriptions). Pain was analyzed by the proportion of time patients reported levels of moderate-severe pain (i.e., pain level ≥ 4). The effects of opioid exposure, prognosis of tumor type ( &lt; 1 year vs ≥ 1 year), and gender on overall survival were analyzed in univariable and multivariable models. Results: Patients in the HOE (n = 887) and LOE (n = 499) groups were well matched for age, gender, and tumor type. Moderate-severe pain was higher in the HOE group compared to the LOE group (29.3% vs 14.0%). HOE was associated with shorter median survival compared to LOE (7.2 vs 13.2 months, p-value &lt; 0.0001). On multivariable analysis, HOE was associated with shorter overall survival after adjusting for age, gender and tumor prognosis (HR 1.4, 95% CI 1.2- 1.6) (Table). Conclusions: Results support prior studies of advanced prostate and lung cancers, and show early utilization of opioids is a strong prognostic factor for survival. Further prospective investigation on the role of opioid receptors and opioid utilization is urgently needed. [Table: see text]
A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin in cancer patients.
Authors: Masashi Kanai, Yoshihiko Otsuka, Kazunori Otsuka, Takafumi Nishimura, Yukiko Mori, Shigemi Matsumoto, Yuzo Kodama, MIchiya Kawaguchi, Etsuro Hatano, Yoshiki Murakami, Atsushi Imaizumi, Tsutomu Chiba, Jun Nishihira, Hiroyuki Shibata
Journal: Journal of Clinical Oncology (2013)

290 Background: Curcumin is a natural polyphenol derived from turmeric (Curcuma longa). Growing preclinical data suggests that curcumin could be a promising anticancer drug, however, poor bioavailability has been a challenging problem for its clinical application. To overcome this problem, a new form of curcumin (Theracurmin) was developed using a microparticle and surface-controlled drug delivery system. We evaluated the safety and pharmacokinetics of Theracurmin in combination with gemcitabine-based chemotherapy in cancer patients. Methods: Pancreatic or biliary tract cancer patients who failed standard chemotherapy were eligible. Planned Theracurmin doses comprised Level 0: 100 mg/body/day; Level 1: 200 mg/body/day; and Level 2: 400 mg/body/day. Level 1 was selected as a starting dose, and daily oral Theracurmin was added to standard gemcitabine-based chemotherapy. In addition to plasma curcumin levels, quality of life (QOL) score scaled according to the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30), NF-κB activity, cytokine levels (interleukin-6 and tumor necrosis factor–α), and efficacy were investigated. Results: We enrolled 16 patients between February 2011 and January 2012. Peak plasma curcumin levels (median) after Theracurmin administration were 324 ng/mL (range: 47–1,029) at Level 1 and 440 ng/mL (range: 179–1,380) at Level 2. These values were significantly higher than those in our previous data achieved using 8 g of conventional curcumin. Long systemic exposure to high concentrations of curcumin did not increase the incidence of adverse events. Interestingly, fatigue- and functioning-associated QOL scores significantly improved after Theracurmin administration (p&lt; 0.01). Conclusions: Up to 400 mg/body/day of Theracurmin could safely increase plasma curcumin levels in cancer patients receiving gemcitabine-based chemotherapy. Clinical trial information: 000002950.
Variation in the use of intensity-modulated radiation therapy (IMRT) in the state of Michigan: 2005-2010.
Authors: James Hayman, Kent A. Griffith, Reshma Jagsi, Mary Uan-Sian Feng, Jean M. Moran, Tania L. Piotrowski, Lori J. Pierce
Journal: Journal of Clinical Oncology (2012)

219 Background: Interest is growing in value in health care, defined as better outcomes at lower costs. A primary driver of cost in radiation oncology is the use of IMRT. We examined the patterns and correlates of use of IMRT across Michigan using publicly available data. Methods: As a certificate of need state, Michigan requires every radiation oncology facility to report yearly the number of external beam and IMRT treatments delivered. Data for 2005-2008 were obtained through a Freedom of Information Act request of the Michigan Department of Community Health, while 2009-2010 data were available at its website. Percentage of external beam treatments delivered using IMRT (IMRT%) was examined across centers over time and repeated-measures longitudinal linear regression was used to identify factors associated with use. Results: During 2005-2010, 48 to 65 centers reported data. Median IMRT% (range) rose steadily during the study period: 2005 16% (0-64); 2006 21% (0-57); 2007 27% (0-79); 2008 37% (7-85); 2009 41% (0-87) 2010 45% (7-100). There was also significant between-center variation (see table). Regression modeling demonstrated that IMRT% was associated with year (+6.7% per year, p&lt;0.0001), facility type (+7.1% freestanding versus hospital, p&lt;0.11), facility annual volume (+5.0% high volume: 7,000+ versus low: &lt;7,000, p=0.01) and the interaction between year and volume (low volume +2.4% per year versus high volume p&lt;0.02). The significant interaction between year and volume suggests that the greatest IMRT% growth was in low volume centers (6.7% per year versus 4.3% per year for high volume). Conclusions: IMRT utilization has grown steadily across Michigan between 2005 and 2010. There is significant variation in its use that appears to be related in part to facility characteristics. The newly established Michigan Radiation Oncology Quality Collaborative (MROQC) is beginning to explore the use of IMRT in patients with breast and lung cancer statewide to identify those groups of patients where improved outcomes may justify its higher cost. [Table: see text]
Effect of Edmonton Symptom Assessment Scale (ESAS) on symptom data collection in a radiation oncology department.
Authors: Bansi Savla, Puja Venkat, Michael Yu
Journal: Journal of Clinical Oncology (2016)

83 Background: ESAS has been used to examine quality of life and symptom burden of patients undergoing cancer treatment. The purpose of this study is to examine attitudes towards ESAS among patients in a Radiation Oncology clinic in conjunction with the perspective of cancer care professionals, to establish ideal implementation of this tool to improve patient care. Methods: Routine use of ESAS in a single Radiation Oncology Department was initiated in July 2015. Six months after implementation, an anonymous, electronic survey was administered to 50 healthcare providers within this department, including attending physicians, resident physicians, advanced practice nurses, physician assistants, and registered nurses. The survey collected information regarding the value of ESAS with regards to patient care, the numerical value at which an intervention is made, which clinical interventions had been implemented due to patient-reported scores on ESAS, which patient populations benefit from ESAS administration, and how frequently ESAS should be administered. Closed and open questions were included. Results: Out of 50 providers, 36 completed the survey. Of these, 31 reported finding ESAS useful. The most common intervention was questioning the patient further about symptoms (29/36.) ESAS data are being reviewed by clinical teams and stored as part of the patient’s medical record in order to compile longitudinal data. An anonymous paper survey is currently being administered to 50 patients at the end of their radiation treatment or at their first follow-up. The survey will collect information about how well symptoms are being communicated with the clinical team, if symptoms should be added to ESAS, how often ESAS should be administered, which specific clinical interventions were provided due to ESAS, and if ESAS improved the overall patient experience. Conclusions: Our survey from the clinical team supports that ESAS is a useful modality to assess patient symptoms and to improve management for patient symptoms effectively. Our ongoing patient survey will validate these findings. These two surveys will be used to improve systematic collection of symptom data for radiation oncology patients.