Open Access
Effects of a multicomponent exercise program in older adults with non-small-cell lung cancer during adjuvant/palliative treatment: an intervention study
(MDPI, 2020) Rosero Rosero, Ilem Dayana; Ramírez Vélez, Robinson; Martínez Velilla, Nicolás; Cedeño Veloz, Bernardo Abel; Morilla Ruiz, Idoia; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
Clinical intervention studies support the efficacy and safety of exercise programs as a treatment modality for non-small-cell lung cancer (NSCLC) during adjuvant/palliative treatment, but the effectiveness of real-world oncogeriatric services is yet to be established. We aimed to examine the effects of a 10-week structured and individualized multicomponent exercise program on physical/cognitive functioning and mental wellness in elderly patients with NSCLC under adjuvant therapy or palliative treatment. A non-randomized, opportunistic control, longitudinal-design trial was conducted on 26 patients with NSCLC stage I-IV. Of 34 eligible participants, 21 were allocated into two groups: (i) control group (n = 7) received usual medical care; and (ii) intervention group (n =19) received multicomponent program sessions, including endurance, strength, balance, coordination and stretching exercises. Tests included the Short Physical Performance Battery (SPPB), 5-m habitual Gait Velocity Test (GVT), Timed Up & Go Test (TUG), 6-Min Walk Test (6MWT), independence of activities in daily living (IADL), muscular performance, cognitive function, and quality of life, which were measured at baseline and after 10weeks of the program. Results revealed a significant groupxtime interaction for SPPB (p = 0.004), 5-m GVT (p = 0.036), TUG (p = 0.007), and muscular performance (chest and leg power; p < 0.001). Similarly, significant changes were observed between groups for cognitive functioning (p = 0.021) and quality of life for EUROQoL 5D (p = 0.006). Our findings confirm that a multicomponent exercise program improves measures of physical/cognitive functioning and quality of life in the elderly with NSCLC under adjuvant therapy or palliative treatment. This is an interesting and important study that adds to our current body of knowledge on the safety of exercise interventions, especially in the elderly with solid tumors.
Open Access
PD-L1 expression in systemic immune cell populations as a potential predictive biomarker of responses to PD-L1/PD-1 blockade therapy in lung cancer
(MDPI, 2019) Bocanegra Gondán, Ana Isabel; Fernández Hinojal, Gonzalo; Zuazo Ibarra, Miren; Arasanz Esteban, Hugo; García Granda, María Jesús; Hernández, Carlos; Ibañez Vea, María; Hernandez Marin, Berta; Martínez Aguillo, Maite; Lecumberri, María José; Fernández de Lascoiti, Ángela; Teijeira, Lucía; Morilla Ruiz, Idoia; Vera García, Ruth; Escors Murugarren, David; Kochan, Grazyna; Ciencias de la Salud; Osasun Zientziak; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
PD-L1 tumor expression is a widely used biomarker for patient stratification in PD-L1/PD-1 blockade anticancer therapies, particularly for lung cancer. However, the reliability of this marker is still under debate. Moreover, PD-L1 is widely expressed by many immune cell types, and little is known on the relevance of systemic PD-L1+ cells for responses to immune checkpoint blockade. We present two clinical cases of patients with non-small cell lung cancer (NSCLC) and PD-L1-negative tumors treated with atezolizumab that showed either objective responses or progression. These patients showed major differences in the distribution of PD-L1 expression within systemic immune cells. Based on these results, an exploratory study was carried out with 32 cases of NSCLC patients undergoing PD-L1/PD-1 blockade therapies, to compare PD-L1 expression profiles and their relationships with clinical outcomes. Significant differences in the percentage of PD-L1+ CD11b+ myeloid cell populations were found between objective responders and non-responders. Patients with percentages of PD-L1+ CD11b+ cells above 30% before the start of immunotherapy showed response rates of 50%, and 70% when combined with memory CD4 T cell profiling. These findings indicate that quantification of systemic PD-L1+ myeloid cell subsets could provide a simple biomarker for patient stratification, even if biopsies are scored as PD-L1 null
Open Access
Tailored prevention of functional decline through a multicomponent exercise program in hospitalized oncogeriatric patients: study protocol for a randomized clinical trial
(Elsevier, 2023) Martínez Velilla, Nicolás; Arrazubi, Virginia; Zambom Ferraresi, Fabíola; Morilla Ruiz, Idoia; López Sáez de Asteasu, Mikel; Ramírez Vélez, Robinson; Zambom Ferraresi, Fabrício; Casa Marín, Antón de la; Ollo Martínez, Iranzu; Gorospe-García, Itziar; Gurruchaga Sotés, Ibon; Galbete Jiménez, Arkaitz; Cedeño Veloz, Bernardo Abel; Martín-Nevado, L.; Izquierdo Redín, Mikel; Vera García, Ruth; Ciencias de la Salud; Osasun Zientziak; Estadística, Informática y Matemáticas; Estatistika, Informatika eta Matematika
BACKGROUND: Cancer mostly affects older adults, causing a wide variety of diagnostic and therapeutic dilemmas. One of the most important moments in cancer patients is the hospitalization period, in which older patients usually remain bedridden for many hours and this may lead to the appearance of sarcopenia and disability. METHODS: We present the research protocol for a randomized controlled trial that will analyze whether an intervention applied to older patients (≥ 65 years) who are hospitalized for acute medical conditions in an Oncology Department improves function. A total of 240 hospitalized older patients will be recruited in the Hospital Universitario de Navarra, Pamplona, Spain, and they will be randomized. The intervention consists of a multicomponent exercise training program that will take place for 4 consecutive days (2 sessions/day). The control group will receive usual hospital care, which will include physical rehabilitation when needed. The primary end point will be the change in functional capacity from baseline to hospital discharge, assessed with the Short Physical Performance Battery (SPPB). Secondary end points will be changes in cognitive and mood status, quality of life, fatigue, strength (dynamic and handgrip), pain, nutrition, length of stay, falls, readmission rate and mortality at 3 months after discharge. RESULTS: Basal data of the patients included in the RCT are described. The foreseen recruitment will not be achieved due to the context of the Covid pandemic and the significantly different responses observed during the clinical trial in oncogeriatric patients compared to our previous experience in older adults hospitalized for medical reasons. DISCUSSION: If our hypothesis is correct and shows that a multicomponent, individualized and progressive exercise program is an effective therapy for improving the capacity of acutely hospitalized older patients compared to usual care, a change in the current system of hospitalization may be justified in oncogeriatric patients.
Open Access
Early detection of hyperprogressive disease in non-small cell lung cancer by monitoring of systemic T cell dynamics
(MDPI, 2020) Arasanz Esteban, Hugo; Zuazo Ibarra, Miren; Bocanegra Gondán, Ana Isabel; Gato Cañas, María; Martínez Aguillo, Maite; Morilla Ruiz, Idoia; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
Hyperprogressive disease (HPD) is an adverse outcome of immunotherapy consisting of an acceleration of tumor growth associated with prompt clinical deterioration. The definitions based on radiological evaluation present important technical limitations. No biomarkers have been identified yet. In this study, 70 metastatic NSCLC patients treated with anti-PD-1/PD-L1 immunotherapy after progression to platinum-based therapy were prospectively studied. Samples from peripheral blood were obtained before the first (baseline) and second cycles of treatment. Peripheral blood mononuclear cells (PBMCs) were isolated and differentiation stages of CD4 lymphocytes quantified by flow cytometry and correlated with HPD as identified with radiological criteria. A strong expansion of highly differentiated CD28− CD4 T lymphocytes (CD4 THD) between the first and second cycle of therapy was observed in HPD patients. After normalizing, the proportion of posttreatment/pretreatment CD4 THD was significantly higher in HPD when compared with the rest of patients (median 1.525 vs. 0.990; p = 0.0007), and also when stratifying by HPD, non-HPD progressors, and responders (1.525, 1.000 and 0.9700 respectively; p = 0.0025). A cutoff value of 1.3 identified HPD with 82% specificity and 70% sensitivity. An increase of CD28− CD4 T lymphocytes ≥ 1.3 (CD4 THD burst) was significantly associated with HPD (p = 0.008). The tumor growth ratio (TGR) was significantly higher in patients with expansion of CD4 THD burst compared to the rest of patients (median 2.67 vs. 0.86, p = 0.0049), and also when considering only progressors (median 2.67 vs. 1.03, p = 0.0126). A strong expansion of CD28− CD4 lymphocytes in peripheral blood within the first cycle of therapy is an early differential feature of HPD in NSCLC treated with immune-checkpoint inhibitors. The monitoring of T cell dynamics allows the early detection of this adverse outcome in clinical practice and complements radiological evaluation.
Open Access
Effects of an individualised exercise program in hospitalised older adults with cancer: a randomised clinical trial
(Springer, 2025-01-01) Ferrara, Maria Cristina; Zambom Ferraresi, Fabrício; Castillo, A.; Delgado, Marina; Galbete Jiménez, Arkaitz; Arrazubi, Virginia; Morilla Ruiz, Idoia; Zambom Ferraresi, Fabíola; Fernández González de la Riva, María Luisa; Vera García, Ruth; Martínez Velilla, Nicolás; Ciencias de la Salud; Osasun Zientziak; Estadística, Informática y Matemáticas; Estatistika, Informatika eta Matematika; Institute of Smart Cities - ISC; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
We aimed to examine the effects of an individualised multicomponent exercise program on functional outcomes in hospitalised older patients with cancer. Patients aged ¿ 65 were recruited upon admission to a Medical Oncology Department and randomly allocated to receive a multicomponent exercise training program twice daily for five days or standard hospital care. The primary outcome measure was the change in functional status using the Short Physical Performance Battery. This study allocated 30 patients in the Control group and 28 in the intervention group. The mean age was 74.4 years. The intervention group (n = 14) showed significant improvements vs the Control group (n = 20) in the Short Physical Performance Battery (SPPB) (between-group difference, 1.92; 95% CI = 0.80,3.07), knee extension strength (between-group difference 7.72; 95% CI = 1.83,13.8), as well as a significant reduction in fatigue (between-group difference —26.5; 95% CI = —38.6,—13.9). This individualised exercise program appears to have contributed to improving functional abilities and reducing fatigue in hospitalised older cancer patients.
Open Access
Systematic review and meta-analysis of randomized, controlled trials on preoperative physical exercise interventions in patients with non-small-cell lung cancer
(MDPI, 2019) Rosero Rosero, Ilem Dayana; Ramírez Vélez, Robinson; Lucía, Alejandro; Martínez Velilla, Nicolás; Santos Lozano, Alejandro; Valenzuela, Pedro L.; Morilla Ruiz, Idoia; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak
Preoperative physical exercise protocols prior to cancer surgery increased in popularity over recent years; however, the beneficial effect of such protocols is not well established, with conflicting results reported. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effects of different modalities or combinations of preoperative exercise interventions and/or prehabilitation multicomponent training in patients with non-small-cell lung cancer (NSCLC) after surgery on the outcomes related to functional capacity, mental wellness and medical care. We searched in OVID Embase, Pubmed, Cochrane Library, CINAHL, Scopus, and Web of Science. Characteristics of studies and program results and outcome data were extracted. Changes between the intervention and control groups, from baseline to follow-up (standardized mean difference (SMD) or relative risk (RR) with 95% confidence interval (CI) for each intervention was pooled using weighted random-effects models). A total of 676 participants from 10 RCTs were included in the final analysis (aerobic training + inspiratory muscle training, n = 5; aerobic training + strength training + inspiratory muscle training, n = 2; aerobic training + strength training, n = 1; multicomponent training, n = 1; aerobic training alone, n = 1). The results showed intervention-induced improvement in walking endurance (SMD = 0.27; 95% CI, 0.11 to 0.44; I2= 0.0%), peak exercise capacity (SMD = 0.78; 95% CI, 0.35 to 1.21; I2= 76.7%), dyspnoea (SMD = −0.30; 95% CI, −0.51 to −0.10; I2 = 0.0%), risk of hospitalization (SMD = −0.58; 95% CI, −0.97 to −0.20; I2= 70.7%), and postoperative pulmonary complications (relative risk (RR) = 0.50; 95% CI, 0.39 to 0.66; I2= 0.0%). For the functional capacity and medical care parameters, preoperative combined aerobic, resistance, and inspiratory muscle training was shown to be effective if comprising one to four weeks, performing 1–3 sessions per week, with moderate intensity (50% for endurance capacity). Further studies with larger samples and higher methodological quality are needed to clarify the potential benefits of preoperative exercise training for patients with NSCLC.