tbuckley/cabot-search huggingface dataset:
Clinical significance of bolus 5-fluorouracil for recurrent or metastatic colorectal cancer treated with FOLFOX therapy.
Authors: Y. Yoshida, J. Hasegawa, R. Nezu, S. Mikata, Y. Kim, J. Nishimura, M. Hirota, K. Ota, K. Yoshikawa
Journal: Journal of Clinical Oncology (2010)

e14078 Background: In recurrent or metastatic colorectal cancer, a combination of leucovorin and fluorouracil with oxaliplatin (FOLFOX) is a standard first-line regimen. Although a variety of FOLFOX regimens are widely used, the neutropenia caused by FOLFOX is often problematic. The purpose of this study was to evaluate the clinical significance of bolus 5-fluorouracil for recurrent or metastatic colorectal cancer treated with FOLFOX therapy. Methods: From January 2008 to December 2009, 39 patients who had metastatic lesions from colorectal cancer treated with FOLFOX + bevacizumab at the Osaka Rosai Hospital were included. This study compared mFOLFOX6 + bevacizumab (mFF6 + BV) with mFOLFOX7 + bevacizumab (mFF7 + BV) to assess the clinical significance of bolus 5-fluorouracil. Results: Grade 3/4 neutropenia was significantly less in mFF7 + BV (58.8%: median 12 cycles) than in mFF6 + BV (22.7%: median 10 cycles) (p = 0.02). Response rates were 50% in mFF6 + BV and 57.9% in mFF7 + BV (p = N.S.). Relative dose intensities (RDI) during the first four cycles of oxaliplatin were 89% in mFF6 + BV and 94.6% in mFF7 + BV, respectively (p = N.S). Completion rates were 52.9% in mFF6 + BV and 68.2% in mFF7 + BV, respectively (p = N.S.). The main factor of RDI and completion rate decrease was hematologic toxicity. The median PFS was 12.5 months in mFF6 + BV compared with 14.8 months in mFF7 + BV (p = 0.91). Conclusions: The mFOLFOX7 + BV regimen seems beneficial as first-line therapy in recurrent or metastatic colorectal cancer, demonstrating a decreased toxicity with acceptable response rate and PFS. Bolus 5- fluorouracil may be unnecessary in a FOLFOX regimen. Further study is needed to fully evaluate bolus 5-fluorouracil. No significant financial relationships to disclose.
Phase I Study of Veliparib (ABT-888) Combined with Cisplatin and Vinorelbine in Advanced Triple-Negative Breast Cancer and/or<i>BRCA</i>Mutation–Associated Breast Cancer
Authors: Eve T. Rodler, Brenda F. Kurland, Melissa Griffin, Julie R. Gralow, Peggy Porter, Rosa F. Yeh, Vijayakrishna K. Gadi, Jamie Guenthoer, Jan H. Beumer, Larissa Korde, Sandra Strychor, Brian F. Kiesel, Hannah M. Linden, John A. Thompson, Elizabeth Swisher, Xiaoyu Chai, Stacie Shepherd, Vincent Giranda, Jennifer M. Specht
Journal: Clinical Cancer Research (2016)

Cisplatin is synergistic with vinorelbine and the PARP inhibitor veliparib, and has antineoplastic activity in triple-negative breast cancer (TNBC) and BRCA mutation-associated breast cancer. This phase I study assessed veliparib with cisplatin and vinorelbine.A 3+3 dose-escalation design evaluated veliparib administered twice daily for 14 days with cisplatin (75 mg/m(2) day 1) and vinorelbine (25 mg/m(2) days 1, 8) every 21 days, for 6 to 10 cycles, followed by veliparib monotherapy. Pharmacokinetics, measurement of poly(ADP-ribose) in peripheral blood mononuclear cells, and preliminary efficacy were assessed. IHC and gene-expression profiling were evaluated as potential predictors of response.Forty-five patients enrolled in nine dose cohorts plus five in an expansion cohort at the highest dose level and recommended phase II dose, 300 mg twice daily. The MTD of veliparib was not reached. Neutropenia (36%), anemia (30%), and thrombocytopenia (12%) were the most common grade 3/4 adverse events. Best overall response for 48 patients was radiologic response with 9-week confirmation for 17 (35%; 2 complete, 15 partial), and stable disease for 21 (44%). Germline BRCA mutation presence versus absence was associated with 6-month progression-free survival [PFS; 10 of 14 (71%) vs. 8 of 27 (30%), mid-P = 0.01]. Median PFS for all 50 patients was 5.5 months (95% confidence interval, 4.1-6.7).Veliparib at 300 mg twice daily combined with cisplatin and vinorelbine is well tolerated with encouraging response rates. A phase II randomized trial is planned to assess veliparib's contribution to cisplatin chemotherapy in metastatic TNBC and BRCA mutation-associated breast cancer. Clin Cancer Res; 22(12); 2855-64. ©2016 AACR.
The influence of margin width and volume of disease near margin on benefit of radiation therapy after breast-conserving surgery for DCIS: Results of long-term follow-up
Authors: U. Rudloff, E. Brogi, B. McCormick, J. P. Brockway, J. I. Goldberg, C. A. Wynveen, A. S. Reiner, S. Patil, K. J. Van Zee
Journal: Journal of Clinical Oncology (2009)

531 Background: There remains variation in the use of radiation (RT) in women with DCIS, despite prospective randomized trials documenting its benefit in reducing the risk of ipsilateral breast tumor recurrence (IBTR). Methods: Patients with DCIS treated with excision alone or excision plus radiation at our institution from 1991–1995 were identified. A dedicated breast pathologist assessed margin width, number of involved ducts at closest margin, nuclear grade, and presence of necrosis and lobular neoplasia. Pathological variables, age, and presence of palpable mass were tested in uni- and multivariate analysis for association with risk of IBTR and added value of RT. Results: 294 patients with a median follow-up of 11 years had actuarial 10- and 15-year overall IBTR rates of 22 and 29%. For lesions excised with margins of &lt;1mm, 1–9mm, and ≥10mm, the actuarial 10-year IBTR rates were 28, 21, and 19%, respectively. RT reduced adjusted IBTR rates by 62% (12 vs. 28%; p=0.002) for all patients; 83% for lesions with &lt;1mm margins (p=0.002), 70% for 1–9mm (p=0.05), and 27% (p=0.55) for ≥10mm. Following adjustment for other variables, higher volume of disease near the margin was associated with risk of IBTR in the no RT group (HR=3.37, p=0.002) and greater benefit of RT (HR 0.14; p=0.004). Conclusions: Effect of RT on local recurrence risk is influenced by both margin width and number of involved ducts at nearest margin. Patients with higher volume of disease near the margin derive a greater benefit from the addition of RT. Despite margins of ≥10mm, the risk of local recurrence remains substantial in patients with DCIS. [Table: see text] No significant financial relationships to disclose.
UN adopts new global health targets to supersede the millennium goals
Authors: Anne Gulland
Journal: BMJ (2015)

The global community formally adopted the sustainable development goals—the successors to the millennium development goals—at a meeting at the United Nations in New York this weekend.

The sustainable development goals consist of 17 goals and 169 targets, with only one goal focusing on health. Goal 3 is to “ensure healthy lives and promote wellbeing for all ages.”

New health related …
Analysis of Molecular Predictors of Response to 5-Azacitine Treatment in AML and MDS Patients Preemptively Treated for Molecular Relapse of Disease
Authors: Meredith Lilly, Beatrice Haack, Anne Otto, Katja Sockel, Jan Moritz Middeke, Anke Mütherig, Karolin Trautmann, Martin Bornhäuser, Gerhard Ehninger, Uwe Platzbecker, Christian Thiede
Journal: Blood (2014)
Creating An Adolescent and Young Adult Cancer Program: Lessons Learned From Pediatric and Adult Oncology Practice Bases
Authors: Damon Reed, Rebecca G. Block, Rebecca Johnson
Journal: Journal of the National Comprehensive Cancer Network (2014)

Driven by reports of unmet clinical needs and lack of survival improvement, programs for adolescents and young adults (AYAs) with cancer have become increasingly common across the United States during the past 10 years. Programs generally originate from existing pediatric or adult hospitals, serve all or a subset of patients between 15 and 39 years of age at the time of cancer diagnosis, and aim to work collaboratively with other branches of their institution to deliver superior care for AYAs. Until recently, programs responded to local needs and evolved without an established framework for growth. Over the past several years, organizations including NCCN have published guidelines for AYA cancer care and for the development of clinical AYA programs. This article reviews these publications, describes the growth and development of 2 nationally recognized AYA centers--Seattle Children's Hospital and Moffitt Cancer Center--and offers practical suggestions to assist developing AYA programs. AYA oncology is entering a new era of increasing public recognition and nationally coordinated growth, as evidenced by the recent establishment of the Change it Back's Centers of Excellence Program that codifies criteria for excellence in AYA cancer care. AYA programs have the potential to improve care for a vital and underserved patient population, stimulate collaborative research, and enhance relationships with patients, the local community, referring physicians, and donors.
Gc Globulin and Prealbumin Serum Levels in Patients With Cancer and Benign Inflammatory Diseases and in Asymptomatic Smokers
Authors: I Rostenberg, R Rico, R Peñaloza
Journal: JNCI Journal of the National Cancer Institute (1979)

Gc globulin and prealbumin serum levels were determined in a coded serum panel from the National Cancer Institute- Mayo Clinic. Serum samples came from 100 patients with cancer (lung, prostate gland, or gastrointestinal tract), from 50 patients with benign inflammatory diseases from the same organs as those of the cancer patients, and from 50 clinically healthy smokers. No differences were observed among groups in the Gc globulin (vitamin D carrier) serum concentrations; however, pre-albumin (vitamin A carrier) serum levels were decreased for patients with benign inflammatory diseases and for cancer patients; the cancer group showed the greatest decrease.
Cutaneous anaplastic large-cell lymphoma (ALCL): A comparative clinical feature and survival outcome analysis of 52 cases according to primary tumor site
Authors: Woo Jin Lee, Ik Jun Moon, Sang Hyung Lee, Chong Hyun Won, Sung Eun Chang, Jee Ho Choi, Kee Chan Moon, Chan-Sik Park, Jooryung Huh, Mi Woo Lee
Journal: Journal of the American Academy of Dermatology (2016)
Phase I/II trial of the prostate-specific membrane antigen (PSMA)-targeted immunoconjugate MLN2704 in patients (pts) with progressive metastatic castration resistant prostate cancer (CRPC)
Authors: M. I. Milowsky, M. Galsky, D. J. George, J. M. Lewin, C. P. Rozario, T. Marshall, M. Chang, D. M. Nanus, I. J. Webb, H. I. Scher
Journal: Journal of Clinical Oncology (2006)

4500 Background: MLN2704 is an immunoconjugate that utilizes the PSMA-targeted monoclonal antibody MLN591 to deliver the maytansinoid antimicrotubule agent DM1 directly to prostate cancer cells. This multicenter trial was designed to determine the tolerability, optimal dosing schedule and efficacy of MLN2704 in pts with progressive metastatic CRPC. Methods: Pts aged ≥18 yrs with progressive metastatic CRPC received MLN2704 i.v. over 2.5 hr q1wk, q2wks or q3wks for 12 wks, with additional doses permitted in responders. Doses within a given schedule were escalated in 40% increments in the absence of excessive dose-limiting toxicity (DLT). Results: 61 pts have been treated. The most common adverse events (AEs) were nausea, fatigue, and schedule-dependent neurotoxicity. The only DLT was gr 3 hepatic transaminitis in 1/6 pts at 330 mg/m 2 q2wks; the only gr 4 AE was transient neutropenia, in 2 pts (330 mg/m 2 q2wks and q3wks). Declines in PSA were most frequent at 330 mg/m 2 q2wks ( table ), including 49–88% PSA declines in 4/6 pts. However, given the frequency of grade 2–3 peripheral neuropathy an additional cohort is being treated with 330mg/m 2 on days 1 and 15 of a 6-wk cycle. Initial results with this 6-wk schedule indicate PSA declines with a lower incidence of gr 2–3 toxicities, particularly neuropathy. Conclusions: Accrual to the dose-escalation phase is complete. Dose-dependent antitumor effects were seen. Peripheral neuropathy has limited continuous dosing at higher dose levels prompting a schedule change. Accrual to the 6-wk schedule is continuing. [Table: see text] [Table: see text]
Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis. Initial experience of a cancer center in Brazil
Authors: E. Akaishi, C. M. Massumoto, N. Mizumoto, F. Teixeira, A. Coimbra, E. Miyadahira, O. Martins, A. C. Buzaid
Journal: Journal of Clinical Oncology (2005)

2112 Background: Peritoneal Carcinomatosis (PC) may represent a terminal manifestation of malignant abdominal neoplasm. The natural history of PC showed a median survival time between 6 and 8 months. In the last decade the use of Cytoreductive Surgery (CS) with Perioperative Intraperitoneal Chemotherapy (PIC) has been associated with improvements in survival and quality of life. Methods: All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy. All anesthesic procedures, as well as, all peritonectomy procedures were performed by the same anesthesiologist and surgeon. A combination of Cisplatin and Doxorubicin were used for gynecological malignancies in perioperative time, followed by 5-day cycle of intraperitoneal Paclitaxel in the postoperative period. For PC from digestive tract malignancies perioperative chemotherapy with CDDP/Mytomicin were used. The duration of chemotherapy was 90 minutes with a temperature of 41 - 42°C. Results: The study included 26 patients (17 female and 9 male) between October 2002 and November 2004. The median age was 52(range 46–72)years. Nine patients had PC from colorectal cancer, 8 ovarian cancer, 3 peritoneal mesothelioma, 3 appendiceal adenocarcinoma, 1 peritoneal pseudomixoma, 1 suprarenal carcinoma and 1 hepatic fibrolamelar tumor. All patiens had complete cytoreductive surgery (C0). The median operative time was 14,2 hours. The median time in ICU was 1,6 days. Abdominal septic complications occurred in 6 patients. Others abdominal complications as digestive and urinary fistulas and abdominal collections occurred in 3 patients and were treated by nonoperative procedures. Febrile neutropenia, leukopenia and thrombocytopenia occurred in 6 patients.Postoperative complications had associated with heavily pretreated patients. No deaths occurred in this series. Conclusions: With a judicious patients’s selection, the aggressive treatment of cytorreductive surgery combined with perioperative intraperitoneal chemotherapy is feasible. In specialized centers, postoperative complications occurs in an acceptable level. No significant financial relationships to disclose.
Effect of telemonitoring of cardiac implantable electronic devices on healthcare utilization: a meta-analysis of randomized controlled trials in patients with heart failure
Authors: Catherine Klersy, Giuseppe Boriani, Annalisa De Silvestri, Georges H. Mairesse, Frieder Braunschweig, Valeria Scotti, Anna Balduini, Martin R. Cowie, Francisco Leyva
Journal: European Journal of Heart Failure (2016)
Evaluation of quality of life (QoL) in 1,210 patients (pts) with metastatic colorectal cancer (MCRC) treated with capecitabine (X) in Brazil: Udated results from a large pt cohort with analysis as a function of pts’ ECOG PS
Authors: C. A. Beato, B. Van Eyll, M. H. Federico, N. Skare, M. R. Perdicaris, F. A. Franke, C. Oliveira, S. Cabral, R. Ribeiro, O. Gampel
Journal: Journal of Clinical Oncology (2006)

8586 Background: The oral fluoropyrimidine X has superior efficacy and improved safety vs. 5-FU/LV in MCRC and early-stage colon cancer. Consequently, X is replacing 5-FU/LV as the backbone of MCRC therapy and is moving into the adjuvant setting. The QoL benefits of oral agents like X over traditional i.v. drugs are becoming more important in MCRC. Methods: Pts with MCRC who received standard oral X (1,250 mg/m 2 twice daily on days 1–14, every 3 weeks) until progressive disease or unacceptable toxicity completed EORTC QLQ C-30 (v3.0) and CR-38 questionnaires at baseline, before cycle 1, at weeks 7 and 13, and at end of treatment. The proportion of pts with improvement, stabilization or worsening of QoL scores from week 7 was analyzed using linear models with repeated measures (generalized estimating questions technique) and SAS (v8.2). Each questionnaire item was analyzed as a function of pts’ ECOG status before first cycle and the evaluation periods. Results: Here we report QoL findings in 1210 pts (male/female, 51%/49%); median age 60 years (range 20–91); 53% of males and 57% of females had ECOG 0 at baseline. Almost half of the pts completed QoL questionnaires through to the end of treatment. Around 42% of pts who presented ECOG ≥1 had ECOG 0 at the end of treatment. Regardless of the baseline ECOG score, pts had significant improvements (p&lt;0.0001 unless stated) in pain (p&lt;0.0002), stoma-related problems (p=0.0003), defecation problems (p=0.0112), appetite loss (p=0.001), weight loss, insomnia (p=0.0074), constipation, body image (p=0.0142), emotional functioning, social functioning (p=0.0170), financial problems (p=0.0407), future perspective, and global health status (p=0.0003). Conclusions: X was associated with improved QoL, with significant benefits observed in most functional/symptomatic QoL domains. The efficacy, safety and convenience benefits of X as reported previously appear to have a direct impact on QoL. These data support its increasing use in the first-line and adjuvant settings. No significant financial relationships to disclose.
“Wait – You're a conservative?” Political diversity and the dilemma of disclosure
Authors: Jim A. C. Everett
Journal: Behavioral and Brain Sciences (2015)

Abstract Many of the proposed recommendations for remedying the harmful effects of political homogeneity for psychology depend upon conservatives disclosing their political identity. Yet how likely is this, when disclosure is so harmful to the individual? Considering this issue as a social dilemma clarifies the pernicious nature of the problem, as well as suggesting how the dilemma can be resolved.
Abstract 13973: Takotsubo's Cardiomyopathy is Associated with Severe Subarachnoid Hemorrhage: Retrospective Analysis of 1,251 patients
Authors: Thura T Abd, Salim Hayek, Jeh-wei Cheng, Owen Samuels, Stamatios Lerakis
Journal: Circulation (2012)

Background: The relationship between Takotsubo’s cardiomyopathy (TCMP) and severity of subarachnoid hemorrhage (SAH) has not been well described. We hypothesized that patients with severe SAH are more likely to develop TCMP.

Methods: We retrospectively evaluated patients with aneurysmal SAH admitted to the Neurological Intensive Care Unit at a tertiary hospital from January 2004 through December 2009. Patients who had echocardiograms done during hospitalization were identified. TCMP was defined by all four of the following diagnostic criteria: (1) The presence of transient hypokinesis or akinesis in the left ventricular mid and apical segments, or the presence of regional wall motion abnormalities that extend beyond a single epicardial vascular distribution, (2) documentation of resolution of echocardiographic changes (3) new ECG abnormalities (ST-segment elevation or T wave inversion) or elevation of cardiac troponin levels, (4) and changes must not be secondary to coronary artery disease. Severity of SAH was assessed by the Hunt and Hess (H&H) score which ranges from 0 to 5. Fisher’s exact test and logistic regression analysis were used to compare H&H scores of patients with TCMP to those who did not develop cardiomyopathy.

Results: We identified 1,251 patients with aneurysmal SAH. Mean age is 52.8 years. Sixty five percent were women, 52% were white and 30.7% were African American. The mean HH similar to the 16.7% without TCMP (p=0.61).

Conclusion: Severity of aneurysmal subarachnoid hemorrhage as measured by Hunt and Huss score is significantly associated with development of Takotsubo’s cardiomyopathy.
A randomized phase II trial of mapatumumab, a TRAIL-R1 agonist monoclonal antibody, in combination with carboplatin and paclitaxel in patients with advanced NSCLC.
Authors: J. Von Pawel, J. H. Harvey, D. R. Spigel, M. Dediu, M. Reck, C. L. Cebotaru, E. Kumm, G. Gallant, N. Fox, D. R. Camidge
Journal: Journal of Clinical Oncology (2010)

LBA7501 Background: Mapatumumab, a fully human agonist monoclonal antibody, targets and activates the death receptor TRAIL-R1. We conducted this randomized, controlled phase II trial to evaluate mapatumumab in combination with carboplatin and paclitaxel as first-line therapy in advanced non-small call lung cancer (NSCLC). Methods: Patients were required to have histologically or cytologically confirmed Stage IIIB or IV advanced primary NSCLC with measurable disease by RECIST. Patients were randomly assigned to Arm A, paclitaxel 200 mg/m 2 + carboplatin AUC 6.0 (PC); Arm B, PC + mapatumumab 10 mg/kg; or Arm C, PC + mapatumumab 30 mg/kg. Cycles were repeated every 21 days; patients completed up to 6 cycles in the absence of evidence of disease progression or unacceptable toxicity. Patients in Arms B and C could receive additional cycles of mapatumumab in the absence of disease progression. The co-primary endpoints were response rate (RR; complete response + partial response) and progression-free survival (PFS). Images were read by independent radiologists blinded to treatment group assignment, as well as locally. Results: 111 patients were enrolled at 22 sites in 4 countries. Addition of mapatumumab to PC did not improve RR or PFS. RR and PFS, based on the independent read, and overall survival results are summarized below. The results based on local reading also showed no benefit from the addition of mapatumumab to PC. Adverse events were generally balanced across treatment groups; there was no evidence that mapatumumab exacerbated toxicities associated with PC. Conclusions: The results do not support further evaluation of mapatumumab in combination with PC in patients with advanced NSCLC. Additional trials of mapatumumab in other indications are ongoing. [Table: see text] [Table: see text]
Long-term follow-up of a randomized trial comparing conventional paclitaxel and carboplatin with dose-dense weekly paclitaxel and carboplatin in women with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer: JGOG 3016 trial.
Authors: Noriyuki Katsumata, Makoto Yasuda, Seiji Isonishi, Hirofumi Michimae, Eizo Kimura, Daisuke Aoki, Toshiko Jobo, Shoji Kodama, Fumitoshi Terauchi, Hiroshi Tsuda, Toru Sugiyama, Kazunori Ochiai
Journal: Journal of Clinical Oncology (2012)

5003 Background: The primary analysis of the JGOG3016 trial (Lancet 2009, 374:1331) showed that dose-dense weekly administration with paclitaxel and carboplatin (dd-TC) demonstrated statistically significant efficiency over tri-weekly administration withTC (c-TC) as first-line chemotherapy in patients with stage II-IV epithelial ovarian, fallopian tube or primary peritoneal cancer. We report the long-term follow-up results on progression-free survival (PFS) and overall survival (OS). Methods: Patients with stage II to IV ovarian cancer were randomly assigned to receive c-TC (carboplatin AUC 6 and paclitaxel 180 mg/m 2 on day 1) or dd-TC (carboplatin AUC 6 on day 1 and paclitaxel 80 mg/m 2 on day 1, 8, 15). The treatments were repeated every 3 weeks for six cycles; in responding patients, additional three cycles were administered. Results: The analysis included eligible 631 patients. At 6.4 years of median follow-up, there continues to be a highly statistically significant improvement in median PFS in favor of the dd-TC group compared with the c-TC group (28.1 vs. 17.5 months, hazard ratio [HR] 0.75, 95% CI, 0.62-0.91; P=0.0037). Median survival has not yet been reached in the dd-TC group, and OS at 5 years was higher in the dd-TC group than the c-TC group (58.6% vs. 51.0%, HR 0.79, 95% CI, 0.63-0.99; P =0.0448). Conclusions: The dd-TC improves long-term PFS and OS in patients with advanced epithelial ovarian cancer.