Accelerated high-dose radiotherapy alone or combined with either concomitant or sequential chemotherapy; treatments of choice in patients with Non-Small Cell Lung Cancer

<p>Abstract</p> <p>Background</p> <p>Results of high-dose chemo-radiotherapy (CRT), using the treatment schedules of EORTC study 08972/22973 or radiotherapy (RT) alone were analyzed among all patients (pts) with Non Small Cell Lung Cancer (NSCLC) treated with curative intent in our department from 1995–2004.</p> <p>Material</p> <p>Included are 131 pts with medically inoperable or with irresectable NSCLC (TNM stage I:15 pts, IIB:15 pts, IIIA:57 pts, IIIB:43 pts, X:1 pt).</p> <p>Treatment</p> <p>Group I: Concomitant CRT: 66 Gy/2.75 Gy/24 fractions (fx)/33 days combined with daily administration of cisplatin 6 mg/m²: 56 pts (standard).</p> <p>Group II: Sequential CRT: two courses of a 21-day schedule of chemotherapy (gemcitabin 1250 mg/m²d1, cisplatin 75 mg/m2 d2) followed by 66 Gy/2.75 Gy/24 fx/33 days without daily cisplatin: 26 pts.</p> <p>Group III: RT: 66 Gy/2.75 Gy/24 fx/33 days or 60 Gy/3 Gy/20 fx/26 days: 49 pts.</p> <p>Results</p> <p>The 1, 2, and 5 year actuarial overall survival (OS) were 46%, 24%, and 15%, respectively.</p> <p>At multivariate analysis the only factor with a significantly positive influence on OS was treatment with chemo-radiation (P = 0.024) (1-, 2-, and 5-yr OS 56%, 30% and 22% respectively). The incidence of local recurrence was 36%, the incidence of distant metastases 46%.</p> <p>Late complications grade 3 were seen in 21 pts and grade 4 in 4 patients. One patient had a lethal complication (oesophageal). For 32 patients insufficient data were available to assess late complications.</p> <p>Conclusion</p> <p>In this study we were able to reproduce the results of EORTC trial 08972/22973 in a non-selected patient population outside of the setting of a randomised trial. Radiotherapy (66 Gy/24 fx/33 days) combined with either concomitant daily low dose cisplatin or with two neo-adjuvant courses of gemcitabin and cisplatin are effective treatments for patients with locally advanced Non-Small Cell Lung Cancer. The concomitant schedule is also suitable for elderly people with co-morbidity.</p

Predictors for long-term mortality in COPD patients requiring non-invasive positive pressure ventilation for the treatment of acute respiratory failure

Introduction The effectiveness of non-invasive mechanical ventilation (NIV) in the management of COPD patients suffering from acute respiratory failure (ARF) as a consequence of exacerbation of the disease, is well established. However, data on long-term outcomes and their predictors, including the individual response to NIV, are scarce. Objectives To investigate predictors for short- and long-term mortality in this study population. Methods A retrospective cohort study was performed including all patients admitted to the Medium Respiratory Care Unit of Maastricht University Medical Center in Maastricht, the Netherlands, with hospitalized exacerbation of COPD (H-ECOPD) with ARF requiring NIV for the first time between January 2009 and December 2011. An extensive number of potential predictors of outcomes, including the response to NIV, were determined on admission and during hospitalization. Univariate and multivariate logistic regression was used for statistical analysis. Results Seventy-eight consecutive patients with moderate to severe COPD (mean age 71.0 +/- 10.7 years; 48.7% males) were included; In-hospital, 1-year and 2-year mortality rates were 14.1%, 43.6% and 56.4%, respectively. Independent risk factors for 2-year mortality were: advanced age (odds ratio(OR) 1.025; confidence interval (CI) 1.002-1.049;P = 0.037), prolonged NIV use more than 8 days (OR:1.054;CI:1.006-1.104;P = 0.027) and no successful response to NIV (OR:2.392;CI:1.297-4.413;P = 0.005). Conclusion Patients with an H-ECOPD requiring NIV for the first time, constitute a severely ill patient group with high in-hospital and 2-year mortality. This study identified advanced age, NIV use more than 8 days and unsuccessful response to NIV as clinical important independent predictors for long-term mortality

Predictors for long‐term mortality in COPD patients requiring non‐invasive positive pressure ventilation for the treatment of acute respiratory failure

Introduction The effectiveness of non-invasive mechanical ventilation (NIV) in the management of COPD patients suffering from acute respiratory failure (ARF) as a consequence of exacerbation of the disease, is well established. However, data on long-term outcomes and their predictors, including the individual response to NIV, are scarce. Objectives To investigate predictors for short- and long-term mortality in this study population. Methods A retrospective cohort study was performed including all patients admitted to the Medium Respiratory Care Unit of Maastricht University Medical Center in Maastricht, the Netherlands, with hospitalized exacerbation of COPD (H-ECOPD) with ARF requiring NIV for the first time between January 2009 and December 2011. An extensive number of potential predictors of outcomes, including the response to NIV, were determined on admission and during hospitalization. Univariate and multivariate logistic regression was used for statistical analysis. Results Seventy-eight consecutive patients with moderate to severe COPD (mean age 71.0 +/- 10.7 years; 48.7% males) were included; In-hospital, 1-year and 2-year mortality rates were 14.1%, 43.6% and 56.4%, respectively. Independent risk factors for 2-year mortality were: advanced age (odds ratio(OR) 1.025; confidence interval (CI) 1.002-1.049;P = 0.037), prolonged NIV use more than 8 days (OR:1.054;CI:1.006-1.104;P = 0.027) and no successful response to NIV (OR:2.392;CI:1.297-4.413;P = 0.005). Conclusion Patients with an H-ECOPD requiring NIV for the first time, constitute a severely ill patient group with high in-hospital and 2-year mortality. This study identified advanced age, NIV use more than 8 days and unsuccessful response to NIV as clinical important independent predictors for long-term mortality

Longitudinal associations between inflammatory markers and fatigue up to two years after colorectal cancer treatment

BACKGROUND: Fatigue is often reported by colorectal cancer survivors (CRC) and largely impacts their quality of life. Inflammation has been linked to fatigue mainly in breast cancer patients. Therefore, we investigated how inflammation is longitudinally associated with fatigue in CRC survivors, up to 2 years post-treatment. METHODS: A total of 257 patients from the ongoing Energy for life after ColoRectal cancer (EnCoRe) cohort study were included in the analysis. Plasma levels of IL6, IL8, IL10, TNFα, hsCRP, and fatigue were measured at 6 weeks, 6, 12, and 24 months post-treatment. Fatigue was measured through the validated Checklist Individual Strength (CIS total, 20-140), consisting of four subscales - subjective fatigue (8-56), motivation (4-28), physical activity (3-21), and concentration (5-35), and the EORTC QLQ-C30 fatigue subscale (0-100). Linear mixed-models were used to assess the confounder-adjusted longitudinal associations between inflammatory markers and overall fatigue along with the subscales. RESULTS: Mean levels of CIS fatigue decreased from 62.9 at 6 weeks to 53.0 at 24 months. In general, levels of inflammatory markers also decreased over time. No statistically significant longitudinal associations were found between IL6, IL8, IL10, TNFα, and fatigue. Higher levels of hsCRP were associated with more CIS fatigue (β per SD 3.21, 95% CI 1.42; 5.01) and EORTC fatigue (β 2.41, 95% CI 0.72; 4.10). CONCLUSION: Increased levels of hsCRP are longitudinally associated with more post-treatment fatigue in CRC survivors. IMPACT: These findings suggest that low-grade inflammation may play a role in fatigue reported by CRC survivors up to 2 years post-treatment

Longitudinal associations of sedentary behavior and physical activity with body composition in colorectal cancer survivors up to 2 years post treatment

PURPOSE: We investigated longitudinal associations of sedentary behavior, light-intensity physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) with body composition in colorectal cancer (CRC) survivors, between 6 weeks and 24 months post treatment. In addition, we explored whether body composition mediated associations of sedentary behavior and MVPA with fatigue. METHODS: A prospective cohort study was conducted in 459 stage I-III CRC patients recruited at diagnosis. Measurements were performed of accelerometer-assessed sedentary time (hours/day), self-reported LPA and MVPA (hours/week), anthropometric assessment of body mass index (BMI), waist circumference and fat percentage (measures of adiposity), and muscle circumference and handgrip strength (measures of muscle mass/function) repeated at 6 weeks, and 6, 12 and 24 months post treatment. Longitudinal associations of sedentary time and physical activity with body composition were analyzed using confounder-adjusted linear mixed models. Mediation analyses were performed to explore the role of body mass index (BMI) and handgrip strength as mediators in associations of sedentary time and MVPA with fatigue. RESULTS: Less sedentary time and LPA were, independent of MVPA, longitudinally associated with increased handgrip strength, but not with measures of adiposity. More MVPA was associated with increased adiposity and increased handgrip strength. Higher BMI partly mediated associations between higher sedentary time and more fatigue. CONCLUSION: Within the first two years after CRC treatment, changes in sedentary behavior, physical activity and body composition are interrelated and associated with fatigue. Intervention studies are warranted to investigate causality. TRIAL REGISTRATION: The EnCoRe study is registered at trialregister.nl as NL6904 (former ID: NTR7099)