Search

Lung cancer remains the leading cause of cancer‐related death worldwide. Affected patients frequently experience debilitating disease‐related symptoms, including dyspnea, cough, fatigue, anxiety, depression, insomnia, and pain, despite the progresses achieved in term of treatment efficacy. Physical activity and exercise are nonpharmacological interventions that have been shown to improve fatigue, quality of life, cardiorespiratory fitness, pulmonary function, muscle mass and strength, and psychological status in patients with lung cancer. Moreover, physical fitness levels, especially cardiorespiratory endurance and muscular strength, are demonstrated to be independent predictors of survival. Nevertheless, patients with lung cancer frequently present insufficient levels of physical activity and exercise, and these may contribute to quality of life impairment, reduction in functional capacity with skeletal muscle atrophy or weakness, and worsening of symptoms, particularly dyspnea. The molecular bases underlying the potential impact of exercise on the fitness and treatment outcome of patients with lung cancer are still elusive. Counteracting specific cancer cells' acquired capabilities (hallmarks of cancer), together with preventing treatment‐induced adverse events, represent main candidate mechanisms. To date, the potential impact of physical activity and exercise in lung cancer remains to be fully appreciated, and no specific exercise guidelines for patients with lung cancer are available. In this article, we perform an in‐depth review of the evidence supporting physical activity and exercise in lung cancer and suggest that integrating this kind of intervention within the framework of a global, multidimensional approach, taking into account also nutritional and psychological aspects, might be the most effective strategy. Implications for Practice: Although growing evidence supports the safety and efficacy of exercise in lung cancer, both after surgery and during and after medical treatments, most patients are insufficiently active or sedentary. Engaging in exercise programs is particularly arduous for patients with lung cancer, mainly because of a series of physical and psychosocial disease‐related barriers (including the smoking stigma). A continuous collaboration among oncologists and cancer exercise specialists is urgently needed in order to develop tailored programs based on patients' needs, preferences, and physical and psychological status. In this regard, benefit of exercise appears to be potentially enhanced when administered as a multidimensional, comprehensive approach to patients' well‐being. The potential effect of physical activity in lung cancer is not fully understood, and no specific exercise guidelines for lung cancer patients are available. This article reviews the evidence supporting physical activity and exercise in lung cancer and suggests that this type of intervention, along with considerations for the nutritional and psychological aspects of such an intervention, might be the most effective strategy. [ABSTRACT FROM AUTHOR]

Objectives. Trastuzumab (H) and pertuzumab (P) with standard chemotherapy is approved for use in the neoadjuvant setting for human epidermal growth receptor 2 -positive patients. A retrospective analysis was performed of patients treated with dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T), trastuzumab, and pertuzumab (THP) in the neoadjuvant setting. Here, the pathologic complete response (pCR) rates are reported. Methods. An electronic medical record review was conducted of patients treated with HP-based therapy in the neoadjuvant setting from September 1, 2013, to March 1, 2015. Data on patient demographics, stage of breast cancer, pathology reports, surgical data, and information on systemic therapy were collected. The pCR was defined as total (tpCR, ypT0/is ypN0), German Breast Group (GBG) pCR (ypT0 ypN0), breast pCR (bpCR) with in situ disease (ypT0/is) and without in situ disease (ypT0), and explored axillary pCR (ypN0). Results. Charts from 66 patients were reviewed, and 57 patients were evaluable for pCR. Median age was 46 years (range 26-68 years). Median tumor size was 4 cm. Of 57 patients, 53 (93%) had operable breast cancer (T1-3, N0-1, M0). Three patients (5.3%) had locally advanced disease (T2-3, N2-3, M0 or T4a-c, any N, M0), and 1 (1.7%) had inflammatory breast cancer (T4d, any N, M0). Overall, 44 (77%) and 13 (23%) had hormone receptor (HR)-positive and negative diseases, respectively. Median numbers of cycles of neoadjuvant treatment were as follows: AC (4, range 1-4), T (4, range 1-4), trastuzumab (6, range 3-8), and pertuzumab (6, range 2-8). In these 57 patients, the rates of tpCR and bpCR with in situ disease were demonstrated in 41/57 (72%) patients, and the rates of GBG pCR and bpCR without in situ disease were found in 30/57 (53%) patients. Of 26 patients with biopsy-proven lymph nodal involvement, axillary pCR occurred in 22 (85%) patients. Conclusion. At a single center, the tpCR and GBG pCR rates of dd AC followed by THP are high at 72% and 53%, respectively. [ABSTRACT FROM AUTHOR]

Introduction. Myocardial strain imaging and blood biomarkers have been proposed as adjuncts to left ventricular ejection fraction (LVEF) monitoring for the early detection of cardiotoxicity during cancertherapy.We report the results of a preplanned cardiac safety analysis of global longitudinal strain (GLS), and troponin-I (TnI) and brain natriuretic peptide (BNP) levels in the phase II study of paclitaxel, trastuzumab, and pertuzumab (THP) for metastatic HER2-positive breast cancer. Patients and Methods. Patients with 0-1 lines of prior therapy were treated with weekly paclitaxel (80 mg/m²) plus trastuzumab (8 mg/kg loading dose followed by 6 mg/kg) and pertuzumab (840 mg loading dose followed by 420 mg) every 3 weeks. Exploratory endpoints were GLS measured with speckle-tracking echocardiography every 3 months and TnI and BNP levels measured every 6 weeks (immediately pre- and postchemotherapy infusion) at 6 time points. Results. Sixty-seven of 69 enrolled patients were treated with THP: 19 (28%) had hypertension, 8 (12%) had diabetes, 11 (16%) had hyperlipidemia, and 26 (38%) had smoking history. After a median follow-up of 21 months (range: 3-38 months), no patients developed symptomatic heart failure. Two patients (3.0%) experienced asymptomatic LVEF decline (grade 2). The mean GLS (6SD) was 19% ± 2% (baseline), 19% ± 2% (month 6), and 19% ± 3% (month 12). Detectable TnI (>0.06 ng/mL) and elevated BNP (>100 pg/mL) levels were observed in 3 (4.3%) and 2 (3.0%) patients, respectively, but were not associated with LVEF decline. Conclusion. The absence of any significant changes in GLS and cardiac biomarkers (TnI and BNP) further support the cardiac safety of THP in patients with metastatic HER2-positive breast cancer. [ABSTRACT FROM AUTHOR]

Background. Anthracycline-containing chemotherapy (Anth-C) is associated with long-term cardiovascular mortality. Although cardiovascular risk assessment has traditionally focused on the heart, evidence has demonstrated that vascular dysfunction also occurs during and up to 1 year following Anth-C. Whether vascular dysfunction persists long-term or negatively influences cardiac function remains unknown. Hence, the present study evaluated ventricular-arterial coupling, in concert with measures of vascular structure and function, in the years following Anth-C. Methods. Arterial elastance (Ea), end-systolic elastance (Ees), and ventricular-arterial coupling (Ea/Ees) were measured during rest and exercise using echocardiography. Resting vascular function (flow-mediated dilation) and structure (carotid intima-media thickness, arterial stiffness) were also measured. Results. Thirty breast cancer survivors (6.5 6 3.6 years after Anth-C) with normal left ventricular ejection fraction (LVEF) (60%66%) and 30 matched controls were studied. At rest, no differences were found in Ea, Ees, Ea/Ees, or LVEF between groups. The normal exercise-induced increase in Ees was attenuated in survivors at 50% and 75% of maximal workload (p, .01). Ea/Ees was also higher at all workloads in the survivors compared with the controls (p, .01). No differences in vascular structure and function were observed between the two groups (p . .05). Conclusion. In the years after Anth-C, ventricular-arterial coupling was significantly attenuated during exercise, primarily owing to decreased LV contractility (indicated by a reduced Ees). This subclinical dysfunction appears to be isolated to the heart, as no differences in Ea were observed. The previously reported adverse effects of Anth-C on the vasculature appear to not persist in the years after treatment, as vascular structure and function were comparable to controls. [ABSTRACT FROM AUTHOR]

Background. The purpose of this study was to investigate the prognostic importance of functional capacity in patients undergoing allogeneic hematopoietic cell transplantation (HCT) for hematological malignancies. Patients and Methods. Using a retrospective design, 407 patients completed a 6-minute walk distance (6MWD) test to assess functional capacity before HCT; 193 (47%) completed a 6MWD test after hospital discharge. Cox proportional hazards regression was used to estimate the risk of nonrelapse mortality (NRM) and overall survival (OS) according to the 6MWD category (<400 m vs. ≥400 m) and the change in 6MWD (before HCT to discharge) with or without adjustment for Karnofsky performance status (KPS), age, and other prognostic markers. Results. Compared with <400 m, the unadjusted hazard ratio for NRM was 0.65 (95% confidence interval, 0.44-0.96) for a 6MWD ≥400 m. A 6MWD of ≥400 m provided incremental information on the prediction of NRM with adjustment for age (p = .032) but not KPS alone (p = .062) or adjustment for other prognostic markers (p = .099). A significant association was found between the 6MWD and OS (p = .027). A 6MWD of $400 m provided incremental information on the prediction of OS with adjustment for age (p = .032) but not for other prognostic markers (p > .05 for all). Patients presenting with a pre-HCT 6MWD of ≥400 m and experiencing a decline in 6MWD had the highest risk of NRM. Conclusion.The 6MWD is a significant univariate predictor of clinical outcomes but did not provide prognostic information beyond that of traditional prognostic markers in HCT. [ABSTRACT FROM AUTHOR]

BACKGROUND: The purpose of this study was to investigate the extent of pre-exercise participation ('preparticipation') health screening in a heterogeneous cohort of adult cancer patients. METHODS: Patients (n = 413) with histologically confirmed solid or hematologic malignancy were categorized into preparticipation health screening risk stratification based on American College Sports Medicine (ACSM) recommendations. Risk of an exercise-related event was evaluated during a symptom-limited cardiopulmonary exercise test (CPET) with 12-lead electrocardiography (ECG). RESULTS: Participant risk was categorized as low risk (n = 59, 14%), moderate risk (n = 217, 53%), and high risk (n = 137, 33%). Mean peak oxygen consumption was 21.7 ± 6.7 mL/kg(-1) per minute(-1) or 19.5 ± 21.7% below age- and sex-predicted sedentary values. No major serious adverse events or fatal events were observed during CPET procedures. A total of 31 positive ECG tests were observed, for an event rate of 8%. ACSM risk stratification did not predict the risk of a positive test. Age, statin use, antiplatelet therapy use, cardiovascular disease, prior treatment with anthracycline or radiation therapy, and being sedentary were predictors of a positive test (all p < .10). CONCLUSION: The patient risk-stratification profile strongly suggests that the use of formalized preparticipation health screening is required in all oncology scenarios; however, risk of an exercise-induced event is low, suggesting that the use of exercise testing is not required for pre-exercise clearance in the majority of patients. [ABSTRACT FROM AUTHOR]

Molecularly targeted therapeutics (MTT) are the future of cancer systemic therapy. They have already moved from palliative therapy for advanced solid malignancies into the setting of curative-intent treatment for early-stage disease. Cardio-toxicity is a frequent and potentially serious adverse complication of some targeted therapies, leading to a broad range of potentially life-threatening complications, therapy discontinuation, and poor quality of life. Low-cost pleiotropic interventions are therefore urgently required to effectively prevent and/or treat MTT-induced cardiotoxicity. Aerobic exercise therapy has the unique capacity to modulate, without toxicity, multiple gene expression pathways in several organ systems, including a plethora of cardiac-specific molecular and cell-signaling pathways implicated in MTT-induced cardiac toxicity. In this review, we examine the molecular signaling of antiangiogenic and HER2-directed therapies that may underpin cardiac toxicity and the hypothesized molecular mechanisms underlying the cardioprotective properties of aerobic exercise. It is hoped that this knowledge can be used to maximize the benefits of small molecule inhibitors, while minimizing cardiac damage in patients with solid malignancies. [ABSTRACT FROM AUTHOR]

Background. We conducted a meta-analysis to determine the effects of supervised exercise training on peak oxygen consumption (VO2peak) in adults with cancer. Methods. A literature review using Ovid MEDLINE (1950-2010), the Cochrane Central Register of Controlled Trials (1991-2010), AMED (1985-2010), Em- base (1988-2010), PubMed (1966-2010), Scopus (1950-2010), and Web of Science (1950-2010) was performed to identify randomized controlled trials examining the effects of supervised exercise training on measurement of VO2peak (via gas exchange analysis) in adults with cancer. Studies were selected using predetermined criteria, and two independent reviewers extracted data. Weighted mean differences (WMDs) were calculated using random effect models. Results. Six studies evaluated VO2peak involving a total of 571 adult cancer patients (exercise, n = 344; usual care control, n = 227). Pooled data indicated that exer- eise training was associated with a statistically significant increase in VO2peak (WMD, 2.90 ml-kg"1-min~1; 95% confidence interval [CI], 1.16-4.64); however, significant heterogeneity was evident in this estimate (I2, 87%). Usual care (control) was associated with a significant decline in VO2peak from baseline to postinterven- tion (WMD, -1.02 ml-kg^-min"1; 95% CI, -1.46 to -0.58; I2,22%). Sensitivity analyses indicated superior improvements in VO2peak for studies conducted for a shorter duration (<4 months) and following the completion of adjuvant therapy (p-values < .001). Exercise training was not associated with a higher incidence of adverse events, although safety was not rigorously monitored or reported. Conclusions. Supervised exercise training is associated with significant improvements in VO2peak following a diagnosis of early-stage cancer, with minimal adverse events. The Oncologist 2011 ;16:112-120 [ABSTRACT FROM AUTHOR]

Purpose. To investigate the feasibility of longitudinal assessment of functional performance measures in newly diagnosed postsurgical malignant glioma patients. Methods. Patients with histologically confirmed, clinically stable, postsurgical, and previously untreated high-grade glioma (HGG) or low-grade glioma (LGG) were studied. Using a prospective design, all participants performed a cardiopulmonary exercise test with expired gas analysis to assess cardiorespiratory function (VO2peak) immediately following surgical resection (mean, 10 days). Additional functional outcomes were skeletal muscle cross-sectional area (CSA) via magnetic resonance imaging, isokinetic muscle strength (isokinetic dynamometry), and body composition (air displacement plethysmography). Quality of life (QOL) was assessed by the Functional Assessment of Cancer Therapy-Brain scale. All study assessments were repeated at 6 and 24 weeks following surgery. Results. Thirty-five patients (HGG, n=25; LGG, n=10) completed baseline assessments. Of these, 20 HGG (80%) and nine LGG (90%) and 15 HGG (60%) and nine LGG (90%) patients completed study assessments at 6 weeks and 24 weeks, respectively. Intention-to-treat analyses indicated several significant time-by-group interactions, with favorable improvements in functional and QOL endpoints from baseline to 24 weeks in the LGG cohort and unfavorable changes in the HGG cohort. Per-protocol analyses including participants assessed at all three study timepoints indicated significant improvements in VO2peak and fatigue from baseline to 24 weeks in the HGG cohort; peak workload, body composition, and muscle strength improved from baseline to 6 weeks (all pvalues < .05). Conclusions. Longitudinal quantitative functional assessments are safe and feasible among select patients undergoing chemoradiation for primary malignant glioma. Large prospective studies investigating the clinical importance of these measures appear warranted. [ABSTRACT FROM AUTHOR]

Background. Anemia in patients with solid tumors is a common problem that is associated with impaired exercise capacity, increased fatigue, and lower quality of life (QoL). Erythropoiesis-stimulating agents (ESAs) have been shown to improve these outcomes; however, it is unknown if additional benefits can be achieved with aerobic exercise training. Methods. We conducted a single-center, prospective, randomized, controlled trial in 55 mild-to-moderately anemic patients with solid tumors. Patients were randomized to either darbepoetin alfa alone (DAL, n = 29) or darbepoetin alfa plus aerobic exercise training (DEX; n = 26). The DEX group performed aerobic exercise training three times per week at 60%-100% of baseline exercise capacity for 12 weeks. The primary endpoint was QoL assessed by the Functional Assessment of Cancer Therapy--Anemia scale. Secondary endpoints were fatigue, cardiorespiratory fitness (VO2peak), hemoglobin (Hb) response, and darbepoetin alfa dosing. Results. Intention-to-treat analyses indicated significant improvements in QoL and fatigue in both groups over time but there were no between-group differences. The DEX group had a significantly greater VO2peak than the DAL group (mean group difference, +3.0 ml/kg per minute; 95% confidence interval, 1.2- 4.7; p = .001) and there were borderline significant differences in favor of the DEX group for Hb response and darbepoetin alfa dosing. Conclusions. Aerobic exercise training did not improve QoL or fatigue beyond the established benefits of DAL but it did result in favorable improvements in exercise capacity and a more rapid Hb response with lower dosing requirements. Our results may be useful to clinicians despite the more recent restrictions on the indications for ESAs. [ABSTRACT FROM AUTHOR]

Purpose. To examine cardiovascular function and risk profile of postmenopausal women treated with chemoendocrine therapy (CET) for hormone receptor--positive operable breast cancer. Methods. Forty-seven breast cancer patients and 11 age-matched healthy controls were studied. Participants performed a cardiopulmonary exercise test with expired gas analysis and impedance cardiography to assess peak aerobic power (VO2peak) and cardiovascular function (stroke volume, cardiac output, cardiac power output, and cardiac reserve). Traditional (i.e., body mass index, lipid profile, and fasting insulin and glucose) and novel (i.e., C-reactive protein, brain natriuretic peptide) cardiovascular risk biochemical factors were also assessed. Results. Breast cancer patients had significantly lower peak exercise stroke volume (68 ± 9 versus 76 ± 11 ml/ beat), cardiac output (10.4 ± 1.5 versus 11.7 ± 2.4 l/minute), cardiac power output (3.0 ± 0.5 versus 3.5 ± 0.9 Watts), cardiac power output reserve (1.7±0.6 versus 2.4±0.8 Watts), and VO2peak (1.3±0.3 versus 1.6± 0.2 l·min-1) than control subjects (p-values < .05). Patients with the greatest impairment in VO2peak had the worse cardiovascular risk profile. Exploratory analyses revealed several differences in study outcomes between the 26 patients receiving hormonal therapy with tamoxifen (TAM) and the 21 patients receiving aromatase inhibitor (AI) therapy. Conclusion. Breast cancer patients treated with adjuvant CET have a significantly and markedly lower cardiorespiratory fitness and cardiac functional reserve compared with age- and sex-matched controls. AI therapy may be associated with a more unfavorable cardiovascular risk profile than TAM. Prospective studies are required to further investigate the clinical value of these findings. [ABSTRACT FROM AUTHOR]

The primary goal is to ensure that exercise training is safe for all cancer patients without creating unnecessary barriers to exercise participation. On the basis of the study findings, the conclusion that exercise testing does not need to be an aspect of pre‐exercise clearance for the majority of cancer patients remains appropriate. Nevertheless, these findings are preliminary, and it is hoped that they will stimulate further work. [ABSTRACT FROM AUTHOR]