tbuckley/cabot-search huggingface dataset:
Strategic 1-multi-line therapy trial in unresectable wild-type RAS metastatic colorectal cancer : A gercor randomized open-label phase III study.
Authors: Benoist Chibaudel, Christophe Tournigand, Franck Bonnetain, Marine Hug de larauze, Armand De Gramont, Pierre Laurent-Puig, Christophe Louvet, Thierry André, Aimery De Gramont
Journal: Journal of Clinical Oncology (2014)

TPS3648^ Background: Several strategies using chemotherapy and molecular targeted drugs are available for the treatment of unresectable metastatic colorectal cancer. Recent and ongoing randomized trials evaluate chemotherapy with bevacizumab or epidermal growth factor receptor (EGFR) inhibitors, but the prior and/or subsequent lines are not fixed and the imbalanced cross-overs will not allow to interpret overall survival. This STRATEGIC-1 trial is a study designed to determine the best sequence of therapy and to define subset populations that will benefit most from one sequence. Methods: This is an ongoing randomized, two-arm, phase III study comparing two multi-line therapeutic strategies in patients wild-type RAS unresectable metastatic colorectal adenocarcinoma, ECOG PS 0-2 and age ≥ 18years. Randomization is stratified by center, GERCOR prognostic score (using PS and LDH level), prior use of oxaliplatin in adjuvant setting and the extent of metastatic disease. Patients (n=474) are randomized (1:1) to either (arm A) FOLFIRI/cetuximab, followed by an oxaliplatin-based chemotherapy with bevacizumab or (arm B) OPTIMOX/bevacizumab, followed by an irinotecan-based chemotherapy with bevacizumab, followed by anti-EGFR mab (cetuximab or panitumumab) with or without irinotecan. The primary endpoint is Duration of Disease Control (DDC). The sample size was planned for testing the primary variable DDC with a two-sided 5% α type one error and a 10% β type two error (Software: EAST 5.3) and a planned interim analysis. A 33% reduction in the risk of event (HR 0.67) was assumed under H1 in the arm B. Secondary endpoints include OS, HR-QoL, TFS, ORR and PFS per sequence, salvage surgery rate, safety and correlations between biomarkers and clinical outcome. CRC tissue (primary or met.) and blood collection are mandatory for biomarker analyses. Enrolment began in October 2013. Clinical trial information: NCT01910610.
Increased expression of immunoreactive thymic stromal lymphopoetin in severe asthma
Authors: A. Shikotra, D.F. Choy, C.M. Ohri, E. Doran, C.M. Butler, B. Hargadon, M. Shelley, A.R. Abbas, C.D. Austin, J. Jackman, L.C. Wu, Liam Heaney, J.R. Arron, P. Bradding
Journal: Journal of Allergy and Clinical Immunology (2012)
Increased cancer-associated protein biomarker levels at bowel endoscopy and risk of extra-colonic primary cancer.
Authors: Thomas B Piper, Martin H. Hvolris, Emilie Hammer, Ib J. Christensen, Gerard Davis, Barry Dowell, Nils Brunner, Hans J. Nielsen
Journal: Journal of Clinical Oncology (2015)

e14550 Background: 20% of the subjects offered bowel endoscopy due to symptoms of colorectal cancer (CRC) get the diagnosis of diverticula. However, the symptoms may be associated with extra-colonic malignancies, which may remain undetected until the symptoms worsen. In addition to diverticula, soluble cancer-associated biomarkers may help elicit further examinations. The aim was to evaluate a possible association between increased levels of biomarkers at endoscopy with diverticula and the risk of developing a primary extra-colonic malignant disease. Methods: During 2004/05 4,509 subjects with symptoms of CRC were included in a study with collection of blood samples before large bowel endoscopy. Plasma levels of TIMP-1, CEA, CA19-9 and YKL-40 were determined. A subgroup of 1,025 subjects was diagnosed with diverticula. At the cut-point December 31st, 2012, subjects, who had developed a primary extra-colonic malignant disease, were identified. The biomarker levels were separated into three groups: 0 = none increased; 1 = one increased; 2 = two or more increased. The cumulative incidence was estimated with death of any cause as a competing risk. Results: 138 (13%) of the 1,025 subjects were diagnosed with a primary, extra-colonic malignant disease with a median time to final diagnosis of 44 (1-107) months. Univariate analyses of the biomarker levels showed that TIMP-1 (p = 0.0002), CEA (p = 0.039) and CA19-9 (p = 0.036) were significantly associated with extra-colonic malignancy. The significance was retained in a multivariate analysis including the three biomarkers (p = 0.0003). The cumulative incidence at 5 years was: 6.6% , 11.1% and 19.8% in group 0, 1 and 2, respectively. Conclusions: Increased plasma levels of TIMP-1, CEA and CA19-9 at endoscopy with findings of diverticula may elicit subsequent examination for extra-colonic malignancies.
Dose escalation study of <i>nab-</i>paclitaxel followed by carboplatin as first line therapy in advanced non-small cell lung cancer (NSCLC)
Authors: M. J. Hawkins, M. Georgy, A. Makhson, S. Cheporov, O. Sergey, P. Yablonsky, P. Bhar, M. Socinski
Journal: Journal of Clinical Oncology (2006)

7132 Background: Paclitaxel for injection formulated in Cremophor® and ethanol (Taxol®, Cremophor paclitaxel) 225 mg/m 2 and carboplatin area under the curve of 6 mg/min·ml (C6) administered every 3 weeks (q3w) has produced an overall response rate (ORR) of 17% in first line patients (pts) with NSCLC with a 1-year survival of 34% [Schiller et al., NEJM, 2002;346:92]. The aim of this phase II study is to obtain clinical experience with a 130-nanometer albumin-bound form of paclitaxel (Abraxane®, ABI-007, nab™ paclitaxel) followed by C6 in NSCLC to determine a dose that approximates the toxicity of Cremophor paclitaxel/C6. Methods: Pts with previously untreated, stage IIIB or IV NSCLC with measurable disease and a life expectancy of over 12 weeks were recruited. In a dose escalation schedule, 4 cohorts (n = 25 each) of successive pts received nab paclitaxel at doses of 225, 260, 300, or 340 mg/m 2 as 30-minute IV infusions followed by C6 q3w. The primary endpoints were the ORR (pts with an objective, confirmed complete or partial response) and toxicity. The primary efficacy analysis was based on all pts who received at least 1 dose of nab-paclitaxel and C6. Stable disease (SD) at ≥16 weeks was also assessed. Results: One hundred pts (100% white; 78% male; median age, 63; performance status score: 0 [11%], 1 [89%] were enrolled from 15 March–28 June of 2005. Accrual was completed in each cohort and serious adverse events reviewed prior to accrual at the next dose level. The results for ORR and SD at ≥16 weeks currently available are shown in the Table . The most common toxicities (any grade) were neutropenia, 43%; fatigue, 37%; sensory neuropathy, 37%; nausea, 35%; thrombocytopenia, 33%; anemia, 24%; alopecia, 24%; and vomiting, 21%. Conclusions: The combination demonstrated antitumor activity and was reasonably well tolerated. Mature data will be presented. [Table: see text] [Table: see text]
Hippocampal memory impairment in breast cancer survivors after chemotherapy measurement using covert testing.
Authors: Anthony J. Ryals, Alexandra C. Apple, Jane X. Wang, David Cella, Frank J. Penedo, Lei Wang, Joel L. Voss
Journal: Journal of Clinical Oncology (2015)

1024 Background: Cognitive impairments are frequently reported following adjuvant chemotherapy, yet potential neuropathological substrates remain uncertain. Chemotherapy and anti-estrogen therapy have neurotoxic effects in rodent models, with disproportionate impairment of the structure and function of the hippocampus, a critical structure for long-term declarative and relational memory. To date, there have been no detailed assessments of human hippocampal function following adjuvant chemotherapy. Methods: We used a specialized test of covert long-term memory processing sensitive to hippocampal impairment, involving eye-movement tracking coupled with functional MRI (fMRI). We compared 13 premenopausal breast cancer survivors on tamoxifen who were within 18 months of completing adjuvant chemotherapy to 14 healthy controls. Results: Relative to controls, patients were not impaired on standard delayed overt recognition memory testing or on neuropsychological tests. In contrast, patients were impaired in eye-movement-based discrimination of repeated visual scenes matched on configural similarity. Impairments were associated with less recruitment of hippocampal activity during covert memory testing. The location of hippocampal relative hypoactivity co-localized with regions of hippocampus that showed significant local volume reductions in survivors, demonstrating concurrence of structural and functional measures of hippocampal impairment. Conclusions: We identified hippocampal and memory abnormalities in breast cancer survivors that were not evident using standard testing. These deficits mapped onto structural measurements of hippocampal atrophy, possibly indicating a neurologic basis of self-reported cognitive difficulties frequently experienced by cancer survivors.
Primary Prevention Implantable Cardioverter Defibrillators in Patients With Nonischemic Cardiomyopathy
Authors: Sana M. Al-Khatib, Gregg C. Fonarow, Jose A. Joglar, Lurdes Y. T. Inoue, Daniel B. Mark, Kerry L. Lee, Alan Kadish, Gust Bardy, Gillian D. Sanders
Journal: JAMA Cardiology (2017)

Conflicting data have emerged on the efficacy of implantable cardioverter defibrillators (ICDs) for primary prevention of sudden cardiac death (primary prevention ICDs) in patients with nonischemic cardiomyopathy.To investigate the association of primary prevention ICDs with all-cause mortality in patients with nonischemic cardiomyopathy.PubMed was searched from January 1, 2000, through October 31, 2016, for the terms implantable defibrillator OR implantable cardioverter defibrillator AND non-ischemic cardiomyopathy. Additional references were identified from bibliographies of pertinent articles and queries to experts in this field.Inclusion criteria consisted of a randomized clinical trial design and comparison of the ICD with medical therapy (control) in at least 100 patients with nonischemic cardiomyopathy. In addition, studies had to report on all-cause mortality during a follow-up period of at least 12 months and be published in English. The search yielded 10 studies, of which only 1 met the inclusion criteria. A search of bibliographies of pertinent articles and queries of experts in this field led to 3 additional studies.The PRISMA guidelines were used to abstract data and assess data quality and validity. Data were pooled using fixed- and random-effects models.The primary end point was all-cause mortality. Before data collection started, primary prevention ICDs were hypothesized to reduce all-cause mortality among patients with nonischemic cardiomyopathy.Four randomized clinical trials met the selection criteria and included 1874 unique patients; 937 were in the ICD group and 937 in the control group. Pooling data from these trials showed a significant reduction in all-cause mortality with an ICD (hazard ratio, 0.75; 95% CI, 0.61-0.93; P = .008; P = .87 for heterogeneity).Primary prevention ICDs are efficacious at reducing all-cause mortality among patients with nonischemic cardiomyopathy. These findings support professional guidelines that recommend the use of ICDs in such patients.
Response rate and bridging to hematopoietic stem cell transplantation (HSCT) with quizartinib (AC220) in patients with FLT3-ITD positive or negative relapsed/refractory AML after second-line chemotherapy or previous bone marrow transplant.
Authors: Jorge E. Cortes, Alexander E. Perl, Hervé Dombret, Hartmut Dohner, Bjoern Steffen, Philippe H. Rousselot, Giovanni Martinelli, Elihu Estey, Neil P. Shah, Alan K. Burnett, Guy Gammon, Denise Trone, Mark J. Levis
Journal: Journal of Clinical Oncology (2013)

7012 Background: FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) in acute myeloid leukemia (AML) is associated with early relapse after chemotherapy and poor survival. Relapse after HSCT or failure of salvage chemotherapy in FLT3-ITD AML is rarely associated with subsequent HSCT or durable survival. Quizartinib, an oral FLT3 inhibitor, shows promising activity; a Ph 2 study (n=333) of quizartinib monotherapy (Levis et al, ASH 2012) reported that quizartinib often bridged patients (pts) to HSCT. Methods: 136 FLT3-ITD(+) and 40 FLT3-ITD(-) pts, relapsed/refractory after HSCT or 1-second line regimen, were included. The response category of composite complete remission (CRc) comprised complete remission [CR] + complete remission with incomplete platelet recovery [CRp] + complete remission with incomplete hematologic recovery [CRi]. Results: Quizartinib was discontinued for HSCT in 47/136 FLT3-ITD(+) pts (35%), with 44/47 having at least a PR (2 CRp, 24 CRi, 18 PR). Median overall survival (OS) was 41.5 wks for pts with CRc prior to HSCT and 29 wks for pts with PR. The 1y survival rate was 39% for both response groups. Pts with a CRc (n=36) or PR (n=20) but no HSCT, respectively, had a median OS of 24.5 and 20.9 wks and 1y survival rates of 25% and 5%. Of 27 pts with OS &gt;52 wks, 17 (63%) had HSCT. Quizartinib was discontinued for HSCT in 14/40 FLT3-ITD(-) pts (35%), with 13/14 having at least a PR (1 CR, 1 CRp, 7 CRi, 4 PR). Median OS was not yet reached for pts with CRc, and was 40.7 wks for pts with PR. The 1y survival rate was 78% for pts with CRc and 50% for pts with PR. 8 of these 14 pts had detectable ITD mutation but the level was below the prespecified 10% cutoff. Conclusions: Of clinical significance in these heavily pretreated pts who had failed salvage chemotherapy or HSCT, approximately 1/3 were successfully bridged to potentially curative HSCT, with encouraging 1y survival rates. To extend the potential benefits of FLT3 inhibitor therapy in combination with allogeneic HSCT, studies of maintenance quizartinib to prevent relapse post HSCT are ongoing. Clinical trial information: NCT00989261.
Response and survival in African American (AA) patients (pts) with non-small cell lung cancer (NSCLC) treated with erlotinib (E)
Authors: V. M. Villaflor, R. Kanteti, S. M. Watson, T. Karrison, E. E. Vokes, R. Salgia
Journal: Journal of Clinical Oncology (2009)

e19006 Background: Pts who respond to the EGFR- tyrosine kinase inhibitors (TKI's) frequently have activating mutations in the kinase domain of EGFR or EGFR overexpression. EGFR activating mutations correlate with adenocarcinoma histology, non-smoking history, female gender, and Asian ethnicity. The presence of EGFR kinase domain mutations is predictive of response but, the relationship is not always concordant. Furthermore, mutations may not predict survival benefit with TKI therapy and other factors are likely involved. It has also been determined that EGFR and met can crosstalk, and serve as potential mechanism of resistance in NSCLC. Most data collected to date on response and overall survival with EGFR-TKI's have been in the Caucasian or Asian community. Hence we collected data specific to the AA pt as they tend to have worse outcomes stage for stage. The purpose of this study is to report the response rate, overall survival, progression free survival (PFS) and clinical characteristics of AA pts with NSCLC treated with an EGFR-TKI. We will correlate these data with EGFR mutation and c-Met expression/mutations/amplifications for markers of NSCLC. Methods: We have listed patients with NSCLC receiving E therapy over the past 5 years. We then retrospectively collected demographic data (age, race, sex, and tobacco history), tumor histology, response rates, survival data and duration of response from AA pts treated with E as single agent. The response to E was correlated with outcome. Results: Data from 44 AA pts (27 women, 17 men) on erlotinib were reviewed. Mean age was 67.1 years (range 48–89 yrs), tobacco use (37 positive, 3 negative, and 4 not recorded). Histology included NSCLC not specified-14, squamous cell- 16, adenocarcinoma-11, large cell-1 and 2 not available. Overall response rate of 13.6% (6-PR, 16-SD, 18-progessive disease, and 4 patients lost to follow up). The PFS was 4.0 months; 95% CI: (2.5–6.6 mos) and overall survival 8.6 mos; 95% CI: (7.2–30.9 mos). EGFR mutations and c-Met analysis will be provided by ASCO meeting in May 2009. Conclusions: AA survival and response rates appear similar to previous data seen with all NSCLC patients receiving treatment with EGFR-TKI's. More data and relationship to biomarkers is needed in this population. [Table: see text]
Increased late mortality in underweight survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.
Authors: Emily S. Tonorezos, Lillian R. Meacham, Joanne F. Chou, Chaya S. Moskowitz, Wendy M. Leisenring, Danielle Novetsky Friedman, Charles A. Sklar, Kimberley Jo Dilley, Melissa M. Hudson, Ann C Mertens, Gregory T. Armstrong, Leslie L. Robison, Kevin C. Oeffinger
Journal: Journal of Clinical Oncology (2017)

110 Background: Approximately one-in-ten adult survivors of childhood cancer are underweight. While the consequences of being overweight or obese have been well-described, outcomes among underweight childhood cancer survivors are unknown. Methods: Underweight was defined as a body mass index (BMI)&lt; 18.5 kg/m 2 , calculated from self-reported height and weight on either the baseline or the first follow-up questionnaire from the Childhood Cancer Survivor Study (CCSS). National Death Index provided death data and self-reported subsequent malignant neoplasm were validated by pathology report. Chi-square test was used to examine the association between underweight status (&lt; 8.5 kg/m 2 vs ≥ 18.5 kg/m 2 ) and baseline demographic characteristics. Marginal models with generalized estimating equations were used to evaluate the associations between BMI and outcomes. Results: Of 9454 survivors (median age 35 years old, range 17-58, with an average of 17.5 years from diagnosis), 627 (6.6%) participants were underweight at baseline and had at least two years of additional follow-up. 29 of 184 deaths were among underweight survivors. In univariate analysis, underweight status was more common among females (9.1% vs 4.5 %, p&lt;0.01) and participants with younger age (8.2% for &lt;5 yrs vs. 6.1% for &gt;=5yr, p&lt;.01), lower household income (8.9% for &lt;$20,000 vs. 6.0% for &gt;=$20,000, p&lt;0.01), and a history of a grade 3 to 4 chronic condition (p = 0.05). After adjustment for these factors, in addition to race/ethnicity, prior smoking, and a history of radiation therapy, the odds of all-cause mortality within two years of BMI report was 2.82 (95% CI: 1.64-2.2; p&lt;0.01) for underweight survivors, compared to normal weight survivors. The risk of subsequent malignant neoplasms within two years of BMI report among underweight survivors compared to normal weight survivors was not significantly increased (OR 1.31; 95% CI: 0.60-2.85; p = 0.49). Conclusions: Childhood cancer survivors who are underweight are at significant risk for late mortality that is unrelated to smoking status, chronic illness, or second malignancy. Whether targeted nutritional interventions would ameliorate this risk is unknown.
Clinical outcomes of late relapse in stage I seminoma.
Authors: Ali Hosni, Padraig Richard Warde, Philippe L. Bedard, Michael A. Jewett, Robert James Hamilton, Malcolm J. Moore, Roger Huang, Martin O'Malley, Joan Sweet, Peter W. M. Chung
Journal: Journal of Clinical Oncology (2015)

4537 Background: This study aimed to identify characteristics associated with late relapse (LR) in stage I seminoma and determine clinical outcomes according to timing of relapse. Methods: Between 1981 and 2011, 949 stage I seminoma patients were managed at our institution. Of these, 254 were treated with adjuvant radiotherapy (aRT) and 695 were managed by active surveillance (AS). LR was defined as tumor recurrence more than 2 years after orchiectomy. Treatment at relapse was dependent on initial treatment and disease extent at relapse. Progression free survival (PFS) from end of treatment of first relapse and overall survival (OS) were calculated. Results: At median follow-up of 10.9 years, 129 patients relapsed at median of 12 months; 14 after aRT and 115 on AS. There was no significant difference between the proportion of patients with LR for aRT (3/14; 25%) vs. AS (29/115; 21%) with no specific clinicopathological features were associated with LR. Paraaortic node(s) was the most common relapse site in AS patients either in LR (n = 28, 97%; median size: 2.1 cm) or early relapse (n = 79, 92%; median size: 2 cm), whereas in aRT patients; all LR were in mediastinum, and early relapse was inguinal (n = 4), scrotal (n = 3) and distant (n = 4). Most LR occurred between 2-3 years (n = 14, 44%; 13 of them were AS patients), and 8 of 9 patients who had LR beyond 5 years were on AS. Treatment of first relapse for aRT group consisted of chemotherapy (n = 10), RT (n = 3) and surgery (n = 1); and for the AS group: RT (n = 87), chemotherapy (n = 26) and surgery (n = 2).Only 1 aRT patient developed second relapse. Nine AS patients had second relapse (7 after RT and 2 after chemotherapy) at a median (range) time of 13 (2–48) months. Second relapse was predominantly distant (9/10), however all were successfully salvaged with chemotherapy. The 5-year PFS from end of treatment of first relapse for the whole, aRT and AS groups were similar, 93%. Among AS group, there was no significant difference between early and late relapse in 5-year PFS (91% vs 100%, p= 0.1) or 10-year OS (96%, for both). Conclusions: In stage I seminoma, the extent and pattern of LR is similar to that for early relapse. For AS patients, selective use of RT/chemotherapy for relapse results in excellent outcomes regardless of timing of relapse.