Synergistic activity of oxaliplatin and 5-fluorouracil in patients with metastatic colorectal cancer with progressive disease while on or after 5-fluorouracil

From February 1995 through October 1996, 25 patients with metastatic colorectal cancer showing a clinical resistance to 5-fluorouracil (5-FU) entered this study. Thirteen received oxaliplatin alone and 12 received it in combination with 5-FU. Oxaliplatin was administered at 130 mg/m(2) over a 2-hour infusion every 3 weeks, alone or added either to 5-FU as a continuous infusion at 200 mg/m(2) to 300 mg/m(2) (six patients) or to a 5-FU bolus, 375 mg/m(2), plus leucovorin, 100 mg/m(2) daily for 5 days every 3 weeks (6 patients). Eighty-six of 98 administered cycles were evaluable for toxicity (47 for oxaliplatin plus 5-FU and 39 for oxaliplatin alone). Hematologic toxicity was mild, occurring as grade 2 leukopenia in 23% of the cycles of 5-FU and oxaliplatin and in 5% of the cycles of oxaliplatin alone. The most common toxicity was neurologic (grade 1 to 2 in 60%-6% of the cycles of the combination, respectively, and 68%-10% of oxaliplatin given alone) as hand-foot paresthesia or hypersensitivity to cold. No grade 4 toxicity was reported and only three patients in the 5-FU group developed grade 3 diarrhea. Grade 2 nausea and vomiting occurred in 33% of the cycles when both drugs were given and in 15% when oxaliplatin was administered alone. The combination of oxaliplatin and 5-FU induced four partial remissions (33%; 95% confidence interval, 6%-60%), whereas eight patients of the whole group had stable disease. No response occurred when oxaliplatin was administered as a single agent. The results of this study confirm the antitumor activity of oxaliplatin when added to 5-FU in patients who have metastatic colorectal cancer previously refractory to 5-FU. The possible therapeutic synergy with 5-FU was not accompanied by increased toxicity

The FHI FEL Upgrade Design

Since coming on-line in November 2013, the Fritz-Haber-Institut (FHI) der Max-Planck-Gesellschaft (MPG) Free-Electron Laser (FEL) has provided intense, tunable infrared radiation to FHI user groups. It has enabled experiments in diverse fields ranging from bio-molecular spectroscopy to studies of clusters and nanoparticles, nonlinear solid-state spectroscopy, and surface science, resulting in 50 peer-reviewed publications so far. The MPG has now funded a significant upgrade to the original FHI FEL. A second short Rayleigh range undulator FEL beamline is being added that will permit lasing from 160 microns. Additionally, a 500 MHz kicker cavity will permit simultaneous two-color operation of the FEL from both FEL beamlines over an optical range of 5 to 50 microns by deflecting alternate 1 GHz pulses into each of the two undulators. We will describe the upgraded FHI FEL physics and engineering design and present the plans for two-color FEL operations in November 2020

High-dose ifosfamide plus adriamycin in the treatment of adult advanced soft tissue sarcomas: is it feasible?

Background: Adriamycin (ADM) and ifosfamide (IFO) are the two most active agents in the treatment of soft tissue sarcomas (STS) with a clear dose-response relationship. We evaluated the feasibility and toxicity of a high-dose IFO-plus-ADM combination. Patients and methods: Fourteen patients with advanced disease and nine patients in adjuvant setting received IFO 12.5 g/m(2) in 120-hour continuous infusion with Mesna uroprotection and ADM 20 mg/m(2) on days 1-3 and G-CSF every three weeks. Results: Twenty-three patients received 89 chemotherapy cycles (70 cycles at full dose). Seventeen patients received the planned treatment, and nine patients required dose reductions. We observed grade 3-4 neutropenia in 52 cycles (59%)/20 patients; grade 3-4 thrombocytopenia in 16 cycles (18%)/nine patients; grade 3-4 anaemia in 24 cycles (27%)/11 patients. Eight patients experienced febrile neutropenia and six patients required blood transfusions. Conclusions: While feasible, this regimen showed heavy toxicity. Nevertheless, 74% of the patients were able to complete the planned treatment. Adjustment of the schedule of IFO continuous infusion to improve this combination is currently under investigation

The FHI FEL Upgrade Design

Since coming on-line in November 2013, the Fritz-Haber-Institut (FHI) der Max-Planck-Gesellschaft (MPG) Free-Electron Laser (FEL) has provided intense, tunable infrared radiation to FHI user groups. It has enabled experiments in diverse fields ranging from bio-molecular spectroscopy to studies of clusters and nanoparticles, nonlinear solid-state spectroscopy, and surface science, resulting in 50 peer-reviewed publications so far. A significant upgrade of the FHI FEL is now being prepared. A second short Rayleigh range undulator FEL beamline is being added that will permit lasing from 160 microns. Additionally, a 500 MHz kicker cavity will permit simultaneous two-color operation of the FEL from both FEL beamlines over an optical range of 5 to 50 microns by deflecting alternate 1 GHz pulses into each of the two undulators. We will describe the upgraded FHI FEL physics and engineering design and present the plans for two-color FEL operations in November 2020

The value of competitive employment:In-depth accounts of people with intellectual disabilities

BackgroundIncreasing the societal participation of people with intellectual disabilities via competitive employment requires a full understanding of what this means to them. This paper aims to provide an in‐depth examination of the lived experiences of people with intellectual disabilities in competitive employment.MethodInterviews were conducted with six participants with mild intellectual disability or borderline functioning and good verbal communication skills. Interviews were analysed according to the guidelines of interpretative phenomenological analysis (IPA). Member checks were conducted.ResultsAnalysis yielded three main themes: (a) Building on my life experiences, (b) My place at work and (c) Being a valuable member of society, like everyone else.ConclusionsCompetitive employment could make a substantial contribution to the sense of belonging to society and quality of life of people with intellectual disabilities. Nevertheless, they must cope with stigma‐related obstacles and feelings of being dependent on others in the work environment

In Quest of Neutrino Masses at O{\cal{O}}(eV) Scale

Neutrino oscillation and tritium beta decay experiments taken simultaneously into account are able to access the so far imperceptible absolute neutrino masses at the electronvolt level. The neutrino mass spectrum derived in this way is independent of the nature of neutrinos (Dirac or Majorana). Furthermore, the lack of neutrinoless double beta decay gives additional constraints on the Majorana neutrino mass spectrum. A case of three neutrinos is examined. Influence of different solutions to the solar neutrino deficit problem on the results is discussed. Apart from the present situation, four qualitatively distinct experimental situations which are possible in the future are investigated: when the two decay experiments give only upper bounds on effective neutrino masses, when either one of them gives a positive result, and when both give positive results. The discussion is carried out by taking into account the present experimental errors of relevant neutrino parameters as well as their much more precise expected estimations (e.g. by $\nu$ factories). It is shown in which cases the upgraded decay experiments simultaneously with neutrino oscillation data may be able to fix the absolute scale of the neutrino mass spectrum, answer the question of the neutrino nature and put some light on CP phases in the lepton sector.Comment: 30 pages, 6 figs, to appear in PR

Phase I and pharmacologic study of weekly gemcitabine and paclitaxel in chemo-naïve patients with advanced non-small-cell lung cancer

Background. Gemcitabine (GEM) and paclitaxel (TAX) are active, non-cross-resistant drugs in non-small-cell lung cancer (NSCLC). We performed a phase I study to determine the maximum-tolerated dose (MTD), antitumor activity and pharmacokinetics of GEM and TAX given weekly in chemo-naive patients with advanced NSCLC. Patients and methods: Escalating doses of GEM (800-2000 mg/m(2)) and TAX (60-100 mg/m(2)) were administered on days 1, 8, 15 every 4 weeks to 35 patients with advanced NSCLC. Plasma pharmacokinetics of TAX and GEM was assessed at the three higher dose-levels. Results: Dose-escalation was discontinued in absence of MTD because of increased cumulative toxicity leading to dose modification or treatment delay at levels 6 and 7 (TAX 100 mg/m(2) plus GEM 1750 and, respectively, 2000 mg/m(2)). Hematological toxicity included grade 4 neutropenia in 3% of cycles, grade 3 thrombocytopenia in one cycle and febrile neutropenia in three cycles. Maximal non-hemathological toxicity was grade 3 elevation in serum transaminases and grade 2 neuro-sensory toxicity in 8% and 5% of cycles, respectively. At the two higher dose-levels a non-linear pharmacokinetics of GEM was observed with a remarkable variability of C-max and AUG. No pharmacokinetic interactions were reported. Objectives responses were seen at all dose levels, with an overall response rate of 43% (95% confidence interval (95% CI): 25.5%-62.6%) in 30 evaluable patients. Conclusions: The weekly administration of GEM and TAX is very well tolerated, and has shown promising antitumor activity in NSCLC. In view of the cumulative toxicity and of the pharmacokinetic profile of GEM, doses of 1500 mg/m(2) of GEM and 100 mg/m2 of TAX are recommended for phase II studies

Peptide receptor radiotherapy: a new option for the management of aggressive fibromatosis on behalf of the Italian Sarcoma Group

The management of aggressive fibromatosis (AF) is problematic, and few options are available to patients unsuitable for surgery and resistant to external-beam radiation therapy (EBRT). We report on two patients with fast-growing recurrences of AF resistant to EBRT who obtained protracted clinical benefits with 90Y-DOTATOC. 90Y-DOTATOC should be further investigated in this setting

Roles of computed tomography and [(18)F]fluorodeoxyglucose-positron emission tomography/computed tomography in the characterization of multiple solitary solid lung nodules

The purpose of this study is to compare the performance of multidetector computed tomography (CT) and positron emission tomography/CT (PET/CT) with [(18)F]fluorodeoxyglucose in the diagnosis of multiple solitary lung nodules in 14 consecutive patients with suspicious lung cancer. CT and PET/CT findings were reviewed by a radiologist and nuclear medicine physician, respectively, blinded to the pathological diagnoses of lung cancer, considering nodule size, shape, and location (CT) and maximum standardized uptake value normalized to body weight (SUVbw max). Nodules were judged malignant or benign. The sensitivity, specificity, and accuracy of the two techniques were compared. CT had a sensitivity, specificity, and accuracy of 93.7, 86.7, and 90.3%, respectively, whereas PET/CT had a sensitivity, specificity, and accuracy of 75, 100, and 87.1%, respectively. Clinical management would have been erroneous in two patients by CT alone and in four patients by PET/CT alone. In one patient, the two techniques misdiagnosed the nodules (2 CT and 1 PET/CT). CT and PET/CT have complimentary roles in characterization of multiple solitary pulmonary nodules. Small nodules are poorly characterized by CT, and small-sized low-SUV malignant nodules are difficult to detect with PET/CT

Endocrine-responsive lobular carcinoma of the breast: features associated with risk of late distant recurrence

BACKGROUND: Invasive lobular carcinomas (ILCs) account for 10-15% of all breast cancers. They are characterized by an elevated endocrine responsiveness and by a long lasting risk of relapse over time. Here we report for the first time an analysis of clinical and pathological features associated with the risk of late distant recurrence in ILCs. PATIENTS AND METHODS: We retrospectively analyzed all consecutive patients with hormone receptor-positive ILC operated at the European Institute of Oncology (EIO) between June 1994 and December 2010 and scheduled to receive at least 5\u2009years of endocrine treatment. The aim was to identify clinical and pathological variables that provide prognostic information in the period beginning 5\u2009years after definitive surgery. The cumulative incidence of distant metastases (CI-DM) from 5\u2009years after surgery was the prospectively defined primary endpoint. RESULTS: One thousand eight hundred seventy-two patients fulfilled the inclusion criteria. The median follow-up was 8.7\u2009years. Increased tumor size and positive nodal status were significantly associated with higher risk of late distant recurrence, but nodal status had a significant lower prognostic value in late follow-up period (DM-HR, 3.21; 95% CI, 2.06-5.01) as compared with the first 5\u2009years of follow-up (DM-HR, 9.55; 95% CI, 5.64-16.2; heterogeneity p value 0.002). Elevated Ki-67 labeling index (LI) retained a significant and independent prognostic value even after the first 5\u2009years from surgery (DM-HR, 1.81; 95% CI 1.19-2.75), and it also stratified the prognosis of ILC patients subgrouped according to lymph node status. A combined score, obtained integrating the previously validated Clinical Treatment Score post 5\u2009years (CTS5) and Ki-67 LI, had a strong association with the risk of late distant recurrence of ILCs. CONCLUSION: We identified factors associated with the risk of late distant recurrence in ER-positive ILCs and developed a simple prognostic score, based on data that are readily available, which warrants further validation