Assessing the impact of chemotherapy-induced peripheral neurotoxicity on the quality of life of cancer patients: The introduction of a new measure

Item does not contain fulltextPURPOSE: To investigate the impact of chemotherapy-induced neurotoxicity on daily activities and quality of life (QoL) of cancer patients. METHODS: QoL of all patients visiting the oncological outpatient ward of the Maxima Medical Centre in the Netherlands from October 2006 until March 2007 treated with taxanes, vinca-alkaloids and/or platinum compounds (n = 88) was compared with the QoL of patients that did not receive these treatments yet (n = 43). Patient-reported neuropathy symptoms were evaluated with the newly developed Chemotherapy Induced Neurotoxicity Questionnaire (CINQ) and the Functional Assessment of Cancer Therapy/Gynaecologic Oncology Group/Neurotoxicity (FACT/GOG-Ntx) questionnaire. RESULTS: Patients treated with chemotherapy reported significantly more complaints of neuropathy (p < 0.001) and more paresthesias and dysesthesias in the upper (p < 0.001; p < 0.01) and lower extremities (p < 0.001) compared to those not treated with chemotherapy. They additionally experienced problems with fine motor function (e.g., getting (un)dressed, writing, and picking up small objects). Moreover, cold-induced paresthesias were frequently reported. Overall, patients indicated that their neuropathy had a negative effect on QoL. CONCLUSIONS: The newly developed CINQ and the FACT/GOG-Ntx results suggest a considerable negative impact of patient-reported neuropathy symptoms on daily activities and QoL in cancer patients treated with chemotherapy. However, further validation of the CINQ is needed

Detecting acute neurotoxicity during platinum chemotherapy by neurophysiological assessment of motor nerve hyperexcitability

<p>Abstract</p> <p>Background</p> <p>Platinum-based drugs, such as cisplatin and oxaliplatin, are well-known for inducing chronic sensory neuropathies but their acute and motor neurotoxicities are less well characterised. Use was made of nerve conduction studies and needle electromyography (EMG) to assess motor nerve excitability in cancer patients during their first treatment cycle with platinum-based chemotherapy in this study.</p> <p>Methods</p> <p>Twenty-nine adult cancer patients had a neurophysiological assessment either before oxaliplatin plus capecitabine, on days 2 to 4 or 14 to 20 after oxaliplatin plus capecitabine, or on days 2 to 4 after carboplatin plus paclitaxel or cisplatin, undertaken by a neurophysiologist who was blinded to patient and treatment details. Patients completed a symptom questionnaire at the end of the treatment cycle.</p> <p>Results</p> <p>Abnormal spontaneous high frequency motor fibre action potentials were detected in 100% of patients (n = 6) and 72% of muscles (n = 22) on days 2 to 4 post-oxaliplatin, and in 25% of patients (n = 8) and 13% of muscles (n = 32) on days 14 to 20 post-oxaliplatin, but in none of the patients (n = 14) or muscles (n = 56) tested prior to oxaliplatin or on days 2 to 4 after carboplatin plus paclitaxel or cisplatin. Repetitive compound motor action potentials were less sensitive and less specific than spontaneous high frequency motor fibre action potentials for detection of acute oxaliplatin-induced motor nerve hyperexcitability but were present in 71% of patients (n = 7) and 32% of muscles (n = 32) on days 2 to 4 after oxaliplatin treatment. Acute neurotoxicity symptoms, most commonly cold-induced paraesthesiae and jaw or throat tightness, were reported by all patients treated with oxaliplatin (n = 22) and none of those treated with carboplatin plus paclitaxel or cisplatin (n = 6).</p> <p>Conclusions</p> <p>Abnormal spontaneous high frequency motor fibre activity is a sensitive and specific endpoint of acute oxaliplatin-induced motor nerve hyperexcitability, detectable on EMG on days 2 to 4 post-treatment. Objective EMG assessment of motor nerve excitability could compliment patient-reported symptomatic endpoints of acute oxaliplatin-induced neurotoxicity in future studies.</p

Polarised Quark Distributions in the Nucleon from Semi-Inclusive Spin Asymmetries

We present a measurement of semi-inclusive spin asymmetries for positively and negatively charged hadrons from deep inelastic scattering of polarised muons on polarised protons and deuterons in the range $0.003$1 GeV$^2$. Compared to our previous publication on this subject, with the new data the statistical errors have been reduced by nearly a factor of two. From these asymmetries and our inclusive spin asymmetries we determine the polarised quark distributions of valence quarks and non-strange sea quarks at $Q^2$=10 GeV$^2$. The polarised $u$ valence quark distribution, $\Delta u_v(x)$, is positive and the polarisation increases with $x$. The polarised $d$ valence quark distribution, $\Delta d_v(x)$, is negative and the non-strange sea distribution, $\Delta \bar q(x)$, is consistent with zero over the measured range of $x$. We find for the first moments $\int_0^1 \Delta u_v(x) dx = 0.77 \pm 0.10 \pm 0.08$, $\int_0^1 \Delta d_v(x) dx = -0.52 \pm 0.14 \pm 0.09$ and $\int_0^1 \Delta \bar q(x) dx= 0.01 \pm 0.04 \pm 0.03$, where we assumed $\Delta \bar u(x) = \Delta \bar d(x)$. We also determine for the first time the second moments of the valence distributions $\int_0^1 x \Delta q_v(x) dx$.Comment: 17 page

Dynamic manipulation of mechanical resonators in the high amplitude regime through optical backaction

Cavity optomechanics enables active manipulation of mechanical resonators through backaction cooling and amplification. This ability to control mechanical motion with retarded optical forces has recently spurred a race towards realizing a mechanical resonator in its quantum ground state. Here, instead of quenching optomechanical motion, we demonstrate high amplitude operation of nanomechanical resonators by utilizing a highly efficient phonon generation process. In this regime, the nanomechanical resonators gain sufficient energy from the optical field to overcome the large energy barrier of a double well potential, leading to nanomechanical slow-down and zero frequency singularity, as predicted by early theories . Besides fundamental studies and interests in parametric amplification of small forces, optomechanical backaction is also projected to open new windows for studying discrete mechanical states, and to foster applications. Here we realize a non-volatile mechanical memory element, in which bits are written and reset via optomechanical backaction by controlling the mechanical damping across the barrier. Our study casts a new perspective on the energy dynamics in coupled mechanical resonator - cavity systems and enables novel functional devices that utilize the principles of cavity optomechanics.Comment: 22 pages, 5 figure

Robotic-assisted laparoscopic prostatectomy

Prostate cancer remains a significant health problem worldwide and is the second highest cause of cancer-related death in men. While there is uncertainty over which men will benefit from radical treatment, considerable efforts are being made to reduce treatment related side-effects and in optimising outcomes. This article reviews the development and introduction of robotic-assisted laparoscopic radical prostatectomy (RALP), the results to date, and the possible future directions of RALP

Body mass index and annual increase of body mass index in long-term childhood cancer survivors; relationship to treatment

Evaluation of body mass index (BMI) at final height (FH) and annual BMI increase in adult childhood cancer survivors (CCS) after treatment with anthracyclines, platinum, and/or radiotherapy. BMI (weight/heightA(2)) was calculated retrospectively from diagnosis until FH. The prevalence of underweight (BMI < 18.5 kg/m(2)) and overweight (BMI a parts per thousand yenaEuro parts per thousand 25 kg/m(2))/obesity (BMI a parts per thousand yenaEuro parts per thousand 30 kg/m(2)) at FH was compared with age-matched controls. The association between underweight/overweight at FH and treatment was assessed by multivariate logistic regression. Annual BMI increase after treatment was assessed by multilevel analysis. Analyses were adjusted for age and underweight/overweight at diagnosis, and age at FH. At FH the prevalence of overweight had not increased, while CCS experienced more underweight as compared to controls (14% vs. 4%, P < 0.001). Overweight at FH was associated with cranial/craniospinal radiotherapy (CRT; OR, 2.23; 95% CI, 1.17-4.26) and underweight at FH with anthracyclines > 300 mg/m(2) (OR, 2.84; 95% CI, 1.33-6.06). Annual BMI increase was +0.47 (0.34-0.60) kg/m(2)/year. In CCS, the annual BMI increase was greater in those with CRT a parts per thousand yenaEuro parts per thousand 30 Gy as compared with those with less or no CRT (+0.15 kg/m(2)/year [0.04-0.25 kg/m(2)/year], P = 0.008) and smaller in those with a higher cumulative anthracycline dose (-0.03 kg/m(2)/year [-0.05 to -0.0005 kg/m(2)/year] per 100 mg/m(2), P = 0.046). After treatment with anthracyclines, platinum, and/or radiotherapy, CRT-treated survivors have more overweight at FH, and a greater annual BMI increase, while anthracycline-treated survivors have more underweight at FH and a lower annual BMI increase

Design of the Resistance and Endurance exercise After ChemoTherapy (REACT) study: A randomized controlled trial to evaluate the effectiveness and cost-effectiveness of exercise interventions after chemotherapy on physical fitness and fatigue

<p>Abstract</p> <p>Background</p> <p>Preliminary studies suggest that physical exercise interventions can improve physical fitness, fatigue and quality of life in cancer patients after completion of chemotherapy. Additional research is needed to rigorously test the effects of exercise programmes among cancer patients and to determine optimal training intensity accordingly. The present paper presents the design of a randomized controlled trial evaluating the effectiveness and cost-effectiveness of a high intensity exercise programme compared to a low-to-moderate intensity exercise programme and a waiting list control group on physical fitness and fatigue as primary outcomes.</p> <p>Methods</p> <p>After baseline measurements, cancer patients who completed chemotherapy are randomly assigned to either a 12-week high intensity exercise programme or a low-to-moderate intensity exercise programme. Next, patients from both groups are randomly assigned to immediate training or a waiting list (i.e. waiting list control group). After 12 weeks, patients of the waiting list control group start with the exercise programme they have been allocated to.</p> <p>Both interventions consist of equal bouts of resistance and endurance interval exercises with the same frequency and duration, but differ in training intensity. Additionally, patients of both exercise programmes are counselled to improve compliance and achieve and maintain an active lifestyle, tailored to their individual preferences and capabilities.</p> <p>Measurements will be performed at baseline (t = 0), 12 weeks after randomization (t = 1), and 64 weeks after randomization (t = 2). The primary outcome measures are cardiorespiratory fitness and muscle strength assessed by means of objective performance indicators, and self-reported fatigue. Secondary outcome measures include health-related quality of life, self-reported physical activity, daily functioning, body composition, mood and sleep disturbances, and return to work. In addition, compliance and satisfaction with the interventions will be evaluated. Potential moderation by pre- and post-illness lifestyle, health and exercise-related attitudes, beliefs and motivation will also be assessed. Finally, the cost-effectiveness of both exercise interventions will be evaluated.</p> <p>Discussion</p> <p>This randomized controlled trial will be a rigorous test of effects of exercise programmes for cancer patients after chemotherapy, aiming to contribute to evidence-based practice in cancer rehabilitation programmes.</p> <p>Trial registration</p> <p>This study is registered at the Netherlands Trial Register (NTR2153)</p

Cigarette smoke and lipopolysaccharide induce a proliferative airway smooth muscle phenotype

Background: A major feature of chronic obstructive pulmonary disease (COPD) is airway remodelling, which includes an increased airway smooth muscle (ASM) mass. The mechanisms underlying ASM remodelling in COPD are currently unknown. We hypothesized that cigarette smoke (CS) and/or lipopolysaccharide (LPS), a major constituent of CS, organic dust and gram-negative bacteria, that may be involved in recurrent airway infections and exacerbations in COPD patients, would induce phenotype changes of ASM. Methods: To this aim, using cultured bovine tracheal smooth muscle (BTSM) cells and tissue, we investigated the direct effects of CS extract (CSE) and LPS on ASM proliferation and contractility. Results: Both CSE and LPS induced a profound and concentration-dependent increase in DNA synthesis in BTSM cells. CSE and LPS also induced a significant increase in BTSM cell number, which was associated with increased cyclin D1 expression and dependent on activation of ERK 1/2 and p38 MAP kinase. Consistent with a shift to a more proliferative phenotype, prolonged treatment of BTSM strips with CSE or LPS significantly decreased maximal methacholine- and KCl-induced contraction. Conclusions: Direct exposure of ASM to CSE or LPS causes the induction of a proliferative, hypocontractile ASM phenotype, which may be involved in airway remodelling in COPD

Phase II study of weekly vinorelbine and 24-h infusion of high-dose 5-fluorouracil plus leucovorin as first-line treatment of advanced breast cancer

We prospectively investigated the efficacy and safety of combining weekly vinorelbine (VNB) with weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and leucovorin (LV) in the treatment of patients with advanced breast cancer (ABC). Vinorelbine 25 mg m−2 30-min intravenous infusion, and high-dose 5-FU 2600 mg m−2 plus LV 300 mg m−2 24-h intravenous infusion (HDFL regimen) were given on days 1 and 8 every 3 weeks. Between June 1999 and April 2003, 40 patients with histologically confirmed recurrent or metastatic breast cancer were enrolled with a median age of 49 years (range: 36–68). A total of 25 patients had recurrent ABC, and 15 patients had primary metastatic diseases. The overall response rate for the intent-to-treat group was 70.0% (95% CI: 54–84%) with eight complete responses and 20 partial responses. All 40 patients were evaluated for survival and toxicities. Among a total of 316 cycles of VNB–HDFL given (average: 7.9: range: 4–14 cycles per patient), the main toxicity was Gr3/4 leucopenia and Gr3/4 neutropenia in 57 (18.0%) and 120 (38.0%) cycles, respectively. Gr1/2 infection and Gr1/2 stomatitis were noted in five (1.6%) and 59 (18.7%) cycles, respectively. None of the patients developed Gr3/4 stomatitis or Gr3/4 infection. Gr2/3 and Gr1 hand–foot syndrome was noted in two (5.0%) and 23 (57.5%) patients, respectively. Gr1 sensory neuropathy developed in three patients. The median time to progression was 8.0 months (range: 3–25.5 months), and the median overall survival was 25.0 months with a follow-up of 5.5 to 45+ months. This VNB–HDFL regimen is a highly active yet well-tolerated first-line treatment for ABC