tbuckley/cabot-search huggingface dataset:
Human Immunodeficiency Virus Presenting as Progressive Multifocal Leukoencephalopathy Restricted to the Posterior Fossa
Authors: Ryan D. Schubert, Megan B. Richie
Journal: JAMA Neurology (2017)

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The prognostic impact of the neutrophil-to-lymphocyte ratio in patients with small-cell lung cancer.
Authors: Myoung Hee Kang, Se-Il Go, Seok-Hyun Kim, Haa-na Song, Jung Hun Kang, Gyeong-won Lee
Journal: Journal of Clinical Oncology (2014)

e18550 Background: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are known as prognostic factors for various types of cancer. In this study we assessed the association of NLR and PLR with the prognosis of small-cell lung cancer (SCLC) in patients who received the standard treatment. Methods: We retrospectively reviewed patients who were diagnosed with SCLC and treated with platinum-based chemotherapy from July 2006 to October 2013 in Gyeongsang National University Hospital Regional Cancer Center and Chang-won Samsung Hospital. Results: A total of 187 patients were evaluated. Compared with low NLR (< 4), high NLR (≥ 4) at diagnosis was associated with poor performance status (PS), advanced stage and lower response rate. Median overall survival (OS) and progression-free survival (PFS) were worse in the high NLR group (high vs. low, 11.17 months vs. 9.20 months, p = 0.019 and 6.90 months vs. 5.49 months, p = 0.005, respectively). In contrast, PLR at diagnosis was not associated with OS and PFS (p = 0.467 and p= 0.205, respectively). In multivariate analysis, stage, lactate dehydrogenase and NLR at diagnosis were independent prognostic factors for OS and PFS. Conclusions: NLR is easily measurable and reflects the SCLC prognosis. A future prospective study is warranted to confirm our results.
E1A06: A phase III trial comparing melphalan, prednisone, and thalidomide (MPT) versus melphalan, prednisone, and lenalidomide (MPR) in newly diagnosed multiple myeloma (MM).
Authors: A. Keith Stewart, Susanna J. Jacobus, Rafael Fonseca, Matthias Weiss, Natalie Scott Callander, Asher Alban Akmal Chanan-Khan, Vincent Rajkumar
Journal: Journal of Clinical Oncology (2014)

8511 Background: Melphalan, prednisone and thalidomide (MPT) is an accepted regimen in newly diagnosed MM. Early studies suggested that lenalidomide (R) might be substituted for thalidomide (T) with equal efficacy and less toxicity. We present E1A06, a randomized, multicenter phase 3 trial comparing MPT vs. MPR in pts with untreated, symptomatic, transplant ineligible MM. Methods: The primary objective was PFS differences between pts receiving MPT: M 9 mg/m2 and P 100 mg p.o. each on days 1-4 with T 100 mg daily vs. MPR: M 5 mg/m2and P 100 mg p.o. each on days 1-4 with R 10 mg p.o. on days 1-21. MPT or MPR therapy was continued for twelve 28 day cycles followed by T 100mg or R 10mg daily until relapse. Aspirin prophylaxis was required. Pts were stratified by ISS stage (I-II vs. III) and age (<65 vs. ≥65). Inferiority of MPR was defined as a PFS treatment hazard ratio (HR) of MPT/MPR ≤ 0.82. Secondary objectives included OS between the arms, toxicities, response rates, depth of response and quality of life (QoL) change. Results: 306 pts were enrolled. Treatment arms were balanced for age, ISS stage and other major prognostic factors. Median age was 75.7y. The median follow-up was 40.7 months (m). Median time on therapy was 12m, and 23m for the 46% of pts on maintenance therapy, with no differences by arm. Per protocol partial response rate was 62% (MPT) vs. 61% (MPR) with no difference in VGPR/CR rates (18.8% vs. 23%). Grade ≥3 toxicity was 71.6% (MPT) vs. 56.7% (MPR); p=0.008. By ITT, the median PFS was 21m on MPT and 18.7m on MPR; HR 0.84 [95%CI: 0.64, 1.09]. The null hypothesis of inferiority of MPR was not rejected. Three year OS was identical by arm at 63% and median OS was not significantly different; p=0.476. Second primary malignancies were observed in 17 (MPT) vs. 14 (MPR) pts with incidence rates of 3.47 and 2.01 (/100 person years). DVT/PE occurred in 8.8% vs. 6.7% of pts. QoL analysis favored MPR by induction end; p=0.007. Conclusions: This phase III trial compares the efficacy of MPT and MPR in elderly patients with newly diagnosed MM. Response rates, PFS and OS were similar between the two arms; however, there was significantly better QOL at 12m and lower toxicity with MPR. Clinical trial information: NCT00602641.
Vinflunine (VFL) as second-line chemotherapy for patients with transitional cell carcinoma of the urothelium (TCCU): A multicenter retrospective study.
Authors: Guillermo De Velasco, Isabel Chirivella, Belen Gonzalez-Grajera, Ovidio Fernandez Calvo, Alvaro Pinto, Nicolas Mohedano, Carmen Santander, Daniel E. Castellano
Journal: Journal of Clinical Oncology (2013)

e15620 Background: VFL is the standard chemotherapy in second-line advanced TCCU in Europe (EMA approval 21/09/2009). We set up a multicenter retrospective study to evaluate the efficacy and toxicity of VFL in patients (pts) with advanced TCCU after platinum failure within the framework of routine practice. Methods: Descriptive and retrospective study in pts who had demonstrated prior progression to a platinum-containing chemotherapy regimen at 7 centers. VFL standard dose (280-320/m 2 every three weeks) was administered until progression or unacceptable toxicity. Objective response was evaluated according to RECIST criteria v.1.1. Results: Between April 2010 and December 2012, a total of 45 pts with median age of 68 years (range 47-83) were analyzed. Main characteristics: ECOG 0-1-2 in 7pts (15.6%), 33pts (73.3%), 5pts (11.1%). Mean creatinine clearance was 59 ml/min. Primary sites of disease were bladder 39pts (86.7%), renal pelvis 5pts (11.1%) and prostatic urethra 1pt (2.2%). All pts had previously received platinum-based chemotherapy as a first-line treatment (cisplatin in 45% of pts). Metastatic locations were: 27pts (60%) lymph nodes, 18pts (40%) lung, 13pts (29%) bone and 10pts (22%) liver. The median number of cycles of VFL was 5 (1-18). All pts were assessed for response, one (2.2%) patient presented complete response (CR), 11pts (24.4%) partial response (PR), 18pts (40%) stable disease (SD) and 15pts (33.4%) progressive disease (PD). Median progression-free survival was 4 months (95% CI, 2.2-5.7). Median overall survival (OS) was 11 months (95% CI, 3.5-18). OS at 6 months was 45%. Liver metastasis was the main prognostic factor for OS (p=0.04). Grade 3/4 adverse events included neutropenia 6pts (13%), constipation 4pts (9%), abdominal pain 4pts (9%) and nausea/vomiting 3pts (6%). Conclusions: This retrospective analysis confirm VFL as an active agent in pts progressing after platinum-based combination for advanced TCCU in a daily clinical practice in Spain. As ESMO (Bellmunt J, 2011) and Spanish (Castellano D, 2012) guidelines recommend vinflunine, it should be offered in this setting or alternatively, treatment within a clinical trial.
Ethnic difference of driver mutation frequencies and correlations between driver mutations and histologic subtypes in lung adenocarcinoma.
Authors: Yuki Yamane, Koichi Goto, Akikazu Kawase, Katsuya Tsuchihara, Sachiyo Mimaki, Genichiro Ishii, Hironobu Ohmatsu, Seiji Niho, Kiyotaka Yoh, Shigeki Umemura, Kanji Nagai, Yuichiro Ohe, Atsushi Ochiai, Hiroyasu Esumi
Journal: Journal of Clinical Oncology (2012)

1552 Background: The frequencies of known driver mutation in lung adenocarcinoma from patients in the United States have been reported by the NCI’s Lung Cancer Mutation Consortium (LCMC), indicating driver mutations were detected in 54% (280/516) of tumors. In this report, mutations found: EGFR 17%, KRAS 22%, HER2 0.6%, PIK3CA 1.2%, BRAF 2%, MET amplification 0.6%, MAP2K1 0.4%, NRAS 0.4%, AKT 0%, ALK rearrangements 7%. However little is known about ethnic difference of driver mutation frequencies and correlations between driver mutations and histological subtypes in lung adenocarcinoma. Methods: Known driver mutations in tumors from 97 Japanese patients with lung adenocarcinoma who underwent surgical resection between 1999 and 2003 in National Cancer Center Hospital East were analyzed by next-generation sequencing and confirmed by Sanger sequencing. Correlations between driver mutations and histological subtypes were also assessed. Results: Driver mutations were detected in 72% of tumors. Mutations found: EGFR 57%, KRAS9%, HER2 2%, PIK3CA 2%, BRAF 1%, MET amplification 1%, MAP2K1 0%, NRAS 0%, AKT 0%. Due to the limitation of rearrangement detection by exon-sequencing, ALK rearrangements were not analyzed. Compared with the report by LCMC, the frequency of EGFR mutations was high and that of KRAS mutations was low in the present study. All mutations were mutually exclusive. The number of predominant histological subtypes of tumors harbored EGFR mutations were papillary 28, acinar 3, solid 5, lepidic 19. That with KRAS mutations showed papillary 2, acinar 2, solid 2, lepidic 3, and HER2 mutations showed papillary 1 and acinar 1. Two tumors harbored PIK3CA mutations showed both histological acinar pattern. Each of BRAF mutation and MET amplification showed lepidic and papillary pattern, respectively. Conclusions: It was suggested that there should be ethnic difference of driver mutation frequencies in lung adenocarcinoma between Asian and non-Asian patients, although the details of ethnic distribution included in LCMC study has not been opened. In addition, each driver mutations did not correspond to specific histological subtypes of lung adenocarcinoma.
Multicenter randomized double-blind controlled phase III study of hhpg-19K as prophylactic therapy in patients with advanced non-small cell lung cancer (NSCLC) receiving myelosuppressive chemotherapy.
Authors: Caicun Zhou, Yunchao Huang, Changshan An, Donglin Wang, Jianxing He, Fuxiang Zhou, Gongyan Chen, Yali Li, Changping Wu, Gang Wu, Xia Song, Jianfei Gao, Wei Liu, Baolan Li, Jianhua Shi, Cheng Huang, Ping Yu, Jueping Feng, Yi Liu, Jielai Xia
Journal: Journal of Clinical Oncology (2014)

9614^ Background: HHPG-19K (19K) is a long-acting pegylated recombinant G-CSF that can be dosed only once-per-chemo cycle. The aim of this phase III study was to investigate the efficacy/safety of HHPG-19K as prophylactic therapy in patients with advanced NSCLC treated with myelosuppressive chemotherapy. Methods: Patients were randomized (1:1:1) blindly to three treatment arms to receive 19K 100mg/kg, 6mg fixed dose or CONTROL (saline) in cycle 1. In cycles 2 to 4 following unblinding at the end of cycle 1, patients in CONTROL received short-acting G-CSF at dose of 5μg/kg once daily subcutaneously 48h after chemotherapy while patients randomized in 2 19K arms to receive the same doses as in cycle 1. All patients received 4 cycles of docetaxel (75mg/m2) plus cisplatin (75mg/m2) or carboplatin (AUC=5) per 21 days. The primary endpoint was the incidence of grade 3/4 neutropenia evaluated in cycle 1. Results: 151 chemo-naive patients with histopathology stage III/IV NSCLC enrolled into this study. The distribution of patients' baseline characteristics was well balanced among 3 arms. The incidence of grade 3/4 neutropenia was significantly decreased in patients received 19K 100µg/kg and 6mg-fixed compared to CONTROL in cycle 1 and showed no statistical difference in cycle 2 to 4. Mean duration of grade 3/4 neutropenia and median recovery time from neutropenia for two 19K arms were significantly shorter than that of CONTROL in cycle 1 and were similar in three arms in cycles 2 to 4. Four (8.00%) febrile neutropenia were observed in CONTROL in cycle 1 only. Nausea, fatigue and anorexia were the most common observed adverse events and no statistical difference among three arms in all cycles. Conclusions: This study demonstrated that the efficacy of HHPG-19K (either 100 µg/kg or 6 mg-fixed dose) was superior to placebo treatment and was comparable to short-acting G-CSF as prophylactic use in patients with NSCLC receiving chemotherapy. HHPG-19K was well tolerated and no unexpected adverse events were observed. The 6 mg-fixed dose is more convenient for administration and is recommended in further clinical practice. Clinical trial information: NCT01560195.
The early effect of breast density legislation on mammogram reporting.
Authors: Esther Jieun Lee, Kelli Kam, Seyed S. Pairawan, Kendra Anderson, Cherie Cora, Won Bae, Karen Kazanjian, Gayathri Nagaraj, Sharon S. Lum
Journal: Journal of Clinical Oncology (2015)

1052 Background: Federal legislation mandating mammographic breast density reporting to patients has been introduced to Congress. California enacted breast density notification legislation (SB1538) on April 1, 2013. What, if any, effect legislation has on mammogram reporting is unknown. We sought to determine the impact of legislation on mammographic density reporting. Methods: A retrospective review of consecutive patients undergoing mammography at a tertiary-care institution in California between March 1, 2013 and May 31, 2013 was conducted. Demographic variables and pre- and post- legislation mammogram results were analyzed. Results: Of 2,020 mammograms performed during the study period, 5.4% did not report breast density, leaving 1,911 cases for study. Median patient age was 58 (26-92). Dense breast tissue was reported in 72.3% of cases in the month prior to legislation, compared with 50.1% and 41.3% in the first and second months post-legislation respectively (p < 0.0001). On multivariable logistic regression analysis, dense breast tissue was independently associated with age < 50 (OR 2.42, 95%CI 1.82-3.20 vs ³50), Asian (OR 2.36, 95%CI 1.49-3.72) and Hispanic (OR 1.39, 95%CI 1.04-1.86) vs. white race/ethnicity, and lower BMI ( < 25 OR 2.88, 95%CI 1.66-4.99, vs. ³30). Dense breast tissue was reported less frequently in the first month (April 2013, OR 0.65, 95%CI 0.42-1.00) and second month (May 2013, OR 0.30, 95%CI 0.17-0.52) post-legislation than pre-legislation (March 2013). Conclusions: Differences in breast density reporting pre- and post-legislation demonstrate the need for an objective measure of breast density. Breast density legislation has the potential to disproportionately target young, Asian, and Hispanic women. Health care providers, as well as legislators, should realize the full effects of this law on women undergoing mammograms who may have concerns regarding their results.
Correlation between the toxicity of erlotinib-based treatment and the detection of gene polymorphism of drug metabolic enzyme and multiresistant gene MDR.
Authors: Yi-sheng Huang, Zhiling Zhou, Zhihong Chen, Hong hong Yan, Jinji Yang, Yi-Long Wu
Journal: Journal of Clinical Oncology (2014)

e19061 Background: Erlotinib is a target drug in the treatment of non-small cell lung carcinoma. Subsequent toxic reactions after erlotinib-based therapy significantly vary among individuals. Methods: For the non-small cell lung carcinoma patients who received erlotinib treatment at a conventional dose for more than 1 month, subsequent treatment toxicity was observed. Meantime, the plasma concentration of erlotinib and its metabolites was determined. In addition, the gene polymorphism of cytochrome p450 3A4 enzyme, cytochrome p450 1A2 enzyme, cytochrome p450 2D6 enzyme and the gene polymorphism of multiresistant gene MDR were also analyzed. Then, the correlation among these three detections was statistically evaluated. Pair-wise correlation analysis was performed by using bivariate correlating method. Results: A total of 73 patients were enrolled in this study. Toxic reactions: 9 grade I (12.3%), 37 grade II (50.7%), 21 grade III (28.8%) and 6 grade IV (8.2%). Among the 6 patients with grade IV toxicity, 2 presented with liver damages and 4 had severe rash (exfoliative dermatitis). The severity of toxic reactions positively correlated with the plasma level of erlotinib and its metabolite OSI-420 ( both P=0.000). Cytochrome p450 3A4*18 and cytochrome p450 1A2 G-113A mutation significantly correlated with toxic reactions (P=0.047 and 0.011) and the plasma concentration of erlotinib and its metabolite( all P<0.05). There was no correlation of the mutation of Cytochrome p450 2D6 and multi-resistant gene MDR with toxic reactions and the plasma concentration of erlotinib and its metabolite. Conclusions: The severity of toxic reaction of erlotinib-based treatment correlates with the plasma concentration of erlotinib and its metabolite (OSI-420). Cytochrome p450 3A4*18 and cytochrome p450 1A2G-113A mutation are correlated with the toxic reactions of erlotinib-based therapy and the plasma level of erlotinib and its metabolite. The plasma concentration of erlotinib and its metabolite significantly increase in patients with cytochrome p450 3A4*18 mutation.
Inflammatory response affects the pharmacokinetics (PK) and pharmacodynamics (PD) of imatinib and CGP 74588 in patients with advanced gastro-intestinal-sarcoma (GIST)
Authors: C. Delbaldo, E. Chatelut, M. Ré, A. Deroussent, A. Jambu, A. Mackrodt, A. Lecesne, G. Vassal
Journal: Journal of Clinical Oncology (2004)

2070 Background: PK analyses of Imatinib showed large inter-individual variability in patients with advanced GIST. This study was designed to explore factors affecting PK variability of Imatinib and CGP 74588, along with PK-PD correlations. Methods: Thirty-five patients (26 males; median age 55 yrs, range 28–84 yrs) with advanced GIST, registered in a phase III study, received400 mg/day (d) of Imatinib. Five blood samples were obtained before intake, between 1 and 3 and 6 and 9 hours on d1, prior to next dose on d2 and at steady state on d30 and 60. Imatinib and CGP 74588 plasma levels were quantitated by reverse-phase HPLC coupled with tandem mass spectometry, and analysed by population PK using NONMEM program. We examined the influence of 17 covariates on Imatinib clearance (CL) and apparent CGP 74 588 clearance (CLM/fm, with fm = fraction of Imatinib converted to CGP 74588). These covariates included age, weight, gender, inflammatory proteins, renal, hematological and liver biological values at baseline along with oedema, liver metastasis and occasion (OCC = 0 for PK at d1 or = 1 at d≥ 30). Results: The best regression formulas were: CL = 17.2/(1 + 0.961 * alpha-1-acid glycoprotein [AAG]) and CLM/fm = 164 * (1–0.46 * OCC)/(1 + 1.52 * AAG) (AAG in g/L), showing that both clearances decreased in case of elevated AAG (probably due to higher plasma protein binding). A significant time-dependent decrease in CLM/fm was evidenced with a mean ± SD CGP/Imatinib AUC ratio of 0.25 ± 0.07 at steady state compared to 0.14 ± 0.03 on d1. Hematological toxicity, measured by the relative decrease in absolute neutrophil count (ANC) (Δ ANC = [ANC nadir - ANC on d1]/ANC on d1) and in Δ platelets, was significantly correlated with high exposure to Imatinib (p = 0.0001 and 0.03, respectively). A significant correlation between Δ ANC and AAG was observed on d1 (p < 0.0001). Response and oedema occurrence were not correlated with any PK parameters. Conclusions: Inflammatory response might influence metabolism, disposition and hematological toxicity of Imatinib. (Supported by an IGR, IFR Grant and La Ligue Genevoise contre le Cancer). No significant financial relationships to disclose.
Pretreatment Patient Characteristics Associated with Achieving Bone Marrow Minimal Residual Disease-Free Status with Frontline Fludarabine, Cyclosphosphamide, Rituximab (FCR) Chemoimmunotherapy for CLL,
Authors: William G. Wierda, Susan O'Brien, Alessandra Ferrajoli, Charles Asa Koller, Jan A. Burger, Stefan Faderl, Guillermo Garcia-Manero, Tapan Kadia, Susan Lerner, Michael J Keating
Journal: Blood (2011)
Evaluating an educational intervention to alleviate distress among men with newly-diagnosed prostate cancer and their partners.
Authors: Lindsay Hedden, Richard J Wassersug, Sarah Mahovlich, Phil Pollock, Monita Sundar, Robert H Bell, Larry Goldenberg, Celestia S. Higano
Journal: Journal of Clinical Oncology (2017)

194 Background: Diagnoses of cancer distress both patients and their partners. Providing accurate information about diagnosis and treatment options promotes active and informed decision-making and can decrease distress and anxiety. We sought to determine whether an education session alleviated distress for both prostate cancer (PC) patients and their partners, and whether their partner’s attendance at the session, as well as specific disease, treatment, and socio-demographic characteristics affect changes in distress levels. Methods: The session consists of a 90-minute didactic presentation, followed by an 8- to 10-minute private session with a urologist and radiation oncologist. We assessed distress using the Distress Thermometer (DT) and compared pre- and post-session distress, and change in distress between patients and partners using matched and unmatched t-tests. We also assessed before-the-session anxiety using the Generalized Anxiety Disorder measure (GAD), and decisional certainty using the Decisional Conflict Scale. Results: 71 patients and 48 partners participated in the study. Attending the session led to a significant reduction in median DT score for both patients (4.0 to 3.0, p = 0.0009) and partners (5.0 vs. 4.0, p = 0.0176). Partners reported higher distress both before and after the session compared to patients (4.9 vs. 3.8, p = 0.025 pre-session and 4.2 vs. 3.1, p = 0.032 post-session). The presence of a partner at the session did not appear to affect patients’ pre- or post-session distress nor the success of the session at alleviating distress. Sociodemographic and clinical characteristics had little effect on distress levels. Conclusions: Our study demonstrates that an interdisciplinary education session is equally effective at alleviating distress for both PC patients and their partners. These results can be used to guide the development of supportive care programs more broadly in terms of their ability to address the physiological and psychological needs of PC patients and their families.