Degradation Rate of 5-Fluorouracil in Metastatic Colorectal Cancer: A New Predictive Outcome Biomarker?

BACKGROUND: 5-FU based chemotherapy is the most common first line regimen used for metastatic colorectal cancer (mCRC). Identification of predictive markers of response to chemotherapy is a challenging approach for drug selection. The present study analyzes the predictive role of 5-FU degradation rate (5-FUDR) and genetic polymorphisms (MTHFR, TSER, DPYD) on survival. MATERIALS AND METHODS: Genetic polymorphisms of MTHFR, TSER and DPYD, and the 5-FUDR of homogenous patients with mCRC were retrospectively studied. Genetic markers and the 5-FUDR were correlated with clinical outcome. RESULTS: 133 patients affected by mCRC, treated with fluoropyrimidine-based chemotherapy from 2009 to 2014, were evaluated. Patients were classified into three metabolic classes, according to normal distribution of 5-FUDR in more than 1000 patients, as previously published: poor-metabolizer (PM) with 5-FU-DR ≤ 0,85 ng/ml/106 cells/min (8 pts); normal metabolizer with 0,85 < 5-FU-DR < 2,2 ng/ml/106 cells/min (119 pts); ultra-rapid metabolizer (UM) with 5-FU-DR ≥ 2,2 ng/ml/106 cells/min (6 pts). PM and UM groups showed a longer PFS respect to normal metabolizer group (14.5 and 11 months respectively vs 8 months; p = 0.029). A higher G3-4 toxicity rate was observed in PM and UM, respect to normal metabolizer (50% in both PM and UM vs 18%; p = 0.019). No significant associations between genes polymorphisms and outcomes or toxicities were observed. CONCLUSION: 5-FUDR seems to be significantly involved in predicting survival of patients who underwent 5-FU based CHT for mCRC. Although our findings require confirmation in large prospective studies, they reinforce the concept that individual genetic variation may allow personalized selection of chemotherapy to optimize clinical outcomes.

Predictors of mood disorders in cancer patients' caregivers.

INTRODUCTION: Patients' care has been associated with a high burden of psychological symptoms in caregivers. This study identifies characteristics associated with mood disorders in caregivers of cancer patients. METHODS: One hundred fifty-two caregivers, aged 24-78 years (average age 51; 60 % females), of cancer patients completed Family Strain Questionnaire (FSQ), Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), and Coping Orientations to the Problems Experienced. We combined this information with patient chart abstraction data. RESULTS: Sixty-three percent of females and 38 % of males were scored as positive when screened for mood disorders, as measured by HADS (total score ≥ 16), and 17 and 5 % for emotional distress as measured by IES (total score ≥ 50). High scores in FSQ-satisfaction with family relationships and FSQ-need for more information about cancer, and low scores in FSQ-thoughts about death are reported. FSQ-emotional burden and FSQ-problems in social involvement are the areas more compromised in females, compared to males. Females, compared to males, use emotional-oriented coping strategies more frequently. Factors independently associated with mood disorders included emotional burden, problems in social involvement, and non-attendance of meeting places; help and assistance from public local services (for patients) decreased the risk of mood disorders in caregivers. CONCLUSIONS: Prevalence of mood disorders is high in cancer patients' caregivers. These results highlight the need to develop family intervention strategies to minimize the impact of patient's care on caregivers' mental health.

Patient perception of disease control and psychological distress.

BACKGROUND: Risk perception and efficacy beliefs affect health behavior. The aim of this study was to measure cancer severity and curability (as proxy for risk perception and efficacy beliefs, respectively) and their association with clinical and psychosocial variables. METHODS: A consecutive sample of cancer patients were recruited and assessed for sociodemographic and medical data, patient perception of cancer severity and curability, and quality of life. The main outcome measures were the depression and anxiety components as measured by the Hospital Anxiety and Depression Scale (HADS). RESULTS: Subjective and objective measures of severity and curability were found to be associated. The perception of one's own disease as severe and difficult to cure, as opposed to severe but curable, was strongly associated with depression (OR = 6.93; P = 0.048) when adjusted for potential confounding factors. Factors independently associated with anxiety were the perception of difficulty to cure (OR = 15.73; P = 0.018), having religious beliefs (OR = 49.74; P = 0.013), and metastasis (OR = 18.42; P = 0.015), when adjusted for sex, marital status, site of cancer, and time from diagnosis. Differences in curability beliefs did not affect any quality of life domain. CONCLUSION: Patients and clinicians may have different perceptions of disease and treatment. The perception of control and curability must be taken into account to identify cancer patients who are suffering most and require special medical care, as these factors have an effect on depression and anxiety.

Treatment-related side effects and quality of life in cancer patients.

BACKGROUND: Cancer leads to a complicated pattern of change in quality of life (QoL). OBJECTIVE: The aims of this study were to assess the impact of treatment-related side effects on QoL in cancer patients and to explore which other factors, and to what extent, contribute to explain low QoL scores. METHODS: One hundred twenty-three cancer patients receiving chemotherapy completed the self-administered questionnaires (Medical Outcomes Short-Form-36 (SF-36) and 12-item General Health Questionnaire). Multiple regression analyses were conducted with the SF-36 physical component summary (PCS) and SF-36 mental component summary (MCS) scores as the dependent variables and demographic and clinical factors as independent variables. RESULTS: Seventy-two percent of patients experienced treatment-related side effects, and 32% resulted positive for psychiatric diseases. Two multivariate analyses showed that worse PCS scores, like worse MCS scores, were significantly and independently predicted by treatment-related side effects (odds ratio (OR) = 5.00, 95%CI 1.29-19.45; OR = 8.08, 95%CI 2.03-32.22, respectively) and changes in health over the last 12 months (OR =2.34, 95%CI 1.47-3.76; OR = 3.21, 95%CI 1.90-5.41, respectively), after adjustment for age, gender, years of school, time from cancer diagnosis, and psychiatric disease. CONCLUSIONS: Given the new emphasis on QoL, we suggest that physicians have a responsibility to openly discuss therapy efficacy, prognosis as well as the potential for adverse events with their patients. Changes in health, as perceived by patient, should also be monitored at follow-up.

Predictors of existential and religious well-being among cancer patients.

Well-being and mental health are not only direct functions of amount of stress, but also depend on how people appraise and face critical situations. Spiritual well-being seems to be a central component of psychological health in physically healthy individuals and it offers some protection against end-of-life despair in those with chronic diseases. In this study, 250 out and in-patients with a cancer diagnosis were interviewed with standardised instruments to measure two aspects of spirituality, existential and religious well-being, coping strategies, psychological state, and quality of life (QoL). Using multivariate logistic regression models we found that coping strategies characterized by acceptance and positive reinterpretation of the stressor, and the absence of anxiety disorder, independently increased the likelihood of the existential well-being (Odds Ratio, OR, 7.7, and OR, 4.5, respectively), whereas religious well-being was not significantly associated with these variables. Our findings show that existential and religious well-being may be very different. A spirituality-based intervention could be differently utilized by patients with different beliefs, cognitive and behaviour characteristics. Measure of coping strategies and psychological state should be part of routine management of cancer patients.

Intradermal lymphoscintigraphy at rest and after exercise: a new technique for the functional assessment of the lymphatic system in patients with lymphoedema.

AIM: The aim of this study was to evaluate the effect of implementing a new technique, intradermal injection lymphoscintigraphy, at rest and after muscular exercise on the functional assessment of the lymphatic system in a group of patients with delayed or absent lymph drainage. METHODS: We selected 44 patients (32 women and 12 men; 15 of 44 with upper limb and 29 of 44 with lower limb lymphoedema). Thirty of 44 patients had bilateral limb lymphoedema and 14 of 44 had unilateral disease; 14 contralateral normal limbs were used as controls. Twenty-three patients had secondary lymphoedema after lymphadenectomy and the remaining 21 had idiopathic lymphoedema. Each of the 44 patients was injected with 50 MBq (0.3-0.4 ml) of (99m)Tc-albumin-nanocolloid, which was administered intradermally at the first interdigital space of the affected limb. Two planar static scans were performed using a low-energy general-purpose collimator (acquisition matrix 128 x 128, anterior and posterior views for 5 min), and in which drainage was slow or absent, patients were asked to walk or exercise for 2 min. A postexercise scan was then performed to monitor and record the tracer pathway and the tracer appearance time (TAT) in the inguinal or axillary lymph nodes. RESULTS: The postexercise scans showed that (i) 21 limbs (15 lower and six upper limbs) had accelerated tracer drainage and tracer uptake in the inguinal and/or axillary lymph nodes. Two-thirds of these showed lymph stagnation points; (ii) 27 limbs had collateral lymph drainage pathways; (iii) in 11 limbs, there was lymph drainage into the deeper lymphatic channels, with unusual uptake in the popliteal or antecubital lymph nodes; (iv) six limbs had dermal backflow; (v) three limbs did not show lymph drainage (TAT=not applicable). TAT=15 + or - 3 min, ranging from 12 to 32 min in limbs with lymphoedema versus 5 + or - 2 min, ranging from 1 to 12 min in the contralateral normal limbs (P<0.001). CONCLUSION: Intradermal injection lymphoscintigraphy gives a better imaging of the lymph drainage pathways in a shorter time, including cases with advanced lymphoedema. In some patients with lymphoedema, a 2-min exercise can accelerate tracer drainage, showing several compensatory mechanisms of lymph drainage. The effect of the exercise technique on TAT and lymphoscintigraphy findings could result in a more accurate functional assessment of lymphoedema patients.