Effects of exercise prehabilitation and/or rehabilitation on health-related quality of life and fatigue in patients with non-small cell lung cancer undergoing surgery: A systematic review.

BACKGROUND: This systematic review aimed to appraise the current available evidence regarding the effects of exercise prehabilitation and rehabilitation on perceived health-related quality of life (HRQoL) and fatigue in patients undergoing surgery for non-small cell lung cancer (NSCLC). METHODS: Studies were selected according to Cochrane guidelines and assessed for methodological quality and therapeutic quality (the international CONsensus on Therapeutic Exercise aNd Training (i-CONTENT)). Eligible studies included patients with NSCLC performing exercise prehabilitation and/or rehabilitation and postoperative HRQoL and fatigue up to 90-days postoperatively. RESULTS: Thirteen studies were included. Exercise prehabilitation and rehabilitation significantly improved postoperative HRQoL in almost half of the studies (47%), although none of the studies demonstrated a decrease in fatigue. Methodological quality and therapeutic quality were poor in respectively 62% and 69% of the studies. CONCLUSION: There was an inconsistent effect of exercise prehabilitation and exercise rehabilitation on improving HRQoL in patients with NSCLC undergoing surgery, with no effect on fatigue. Due to the low methodological and therapeutic quality of included studies, it was not possible to identify the most effective training program content to improve HRQoL and reduce fatigue. It is recommended to investigate the impact of a high therapeutic qualified exercise prehabilitation and exercise rehabilitation on HRQoL and fatigue in larger studies.

Feasibility of Rehabilitation during Chemoradiotherapy among Patients with Stage III Non-Small Cell Lung Cancer: A Proof-of-Concept Study.

Rehabilitation during chemoradiotherapy (CHRT) might (partly) prevent reduction in physical fitness and nutritional status and could improve treatment tolerance in patients with stage III non-small cell lung cancer (NSCLC). The aim of this proof-of-concept study was to investigate the feasibility of a multimodal program for rehabilitation during CHRT. A home-based multimodal rehabilitation program (partly supervised moderate-intensity physical exercise training and nutritional support) during CHRT was developed in collaboration with patients with stage III NSCLC and specialized healthcare professionals. A predetermined number of six patients with stage III NSCLC (aged > 50 years) who underwent CHRT and participated in this program were monitored in detail to assess its feasibility for further development and optimization of the program. The patient's level of physical functioning (e.g., cardiopulmonary exercise test, six-minute walking test, handgrip strength, body mass index, fat free mass index, energy and protein intake) was evaluated in order to provide personalized advice regarding physical exercise training and nutrition. The program appeared feasible and well-tolerated. All six included patients managed to perform the assessments. Exercise session adherence was high in five patients and low in one patient. The performed exercise intensity was lower than prescribed for all patients. Patients were motivated to complete the home-based rehabilitation program during CHRT. Preliminary effects on physical and nutritional parameters revealed relatively stable values throughout CHRT, with inter-individual variation. Supervised and personalized rehabilitation in patients with stage III NSCLC undergoing CHRT seems feasible when the intensity of the physical exercise training was adjusted to the possibilities and preferences of the patients. Future research should investigate the feasibility of a supervised and personalized rehabilitation program during CHRT with a low-to-moderate exercise intensity with the aim to prevent physical decline during CHRT.

Implementation of prehabilitation in colorectal cancer surgery: qualitative research on how to strengthen facilitators and overcome barriers.

PURPOSE: Prehabilitation is increasingly offered to patients with colorectal cancer (CRC) undergoing surgery as it could prevent complications and facilitate recovery. However, implementation of such a complex multidisciplinary intervention is challenging. This study aims to explore perspectives of professionals involved in prehabilitation to gain understanding of barriers or facilitators to its implementation and to identify strategies to successful operationalization of prehabilitation. METHODS: In this qualitative study, semi-structured interviews were performed with healthcare professionals involved in prehabilitation for patients with CRC. Prehabilitation was defined as a preoperative program with the aim of improving physical fitness and nutritional status. Parallel with data collection, open coding was applied to the transcribed interviews. The Ottawa Model of Research Use (OMRU) framework, a comprehensive interdisciplinary model guide to promote implementation of research findings into healthcare practice, was used to categorize obtained codes and structure the barriers and facilitators into relevant themes for change. RESULTS: Thirteen interviews were conducted. Important barriers were the conflicting scientific evidence on (cost-)effectiveness of prehabilitation, the current inability to offer a personalized prehabilitation program, the complex logistic organization of the program, and the unawareness of (the importance of) a prehabilitation program among healthcare professionals and patients. Relevant facilitators were availability of program coordinators, availability of physician leadership, and involving skeptical colleagues in the implementation process from the start. CONCLUSIONS: Important barriers to prehabilitation implementation are mainly related to the intervention being complex, relatively unknown and only evaluated in a research setting. Therefore, physicians' leadership is needed to transform care towards more integration of personalized prehabilitation programs. IMPLICATIONS FOR CANCER SURVIVORS: By strengthening prehabilitation programs and evidence of their efficacy using these recommendations, it should be possible to enhance both the pre- and postoperative quality of life for colorectal cancer patients during survivorship.

Study Protocol of the NVALT25-ELDAPT Trial: Selecting the Optimal Treatment for Older Patients With Stage III Non-small-cell Lung Cancer.

BACKGROUND: Patients aged 75 years or older with stage III non-small-cell lung cancer (NSCLC) are underrepresented in clinical trials, leading to a lack of evidence for selection of the optimal treatment strategy. Information on benefits and harms of concurrent chemoradiotherapy among medically fit elderly patients is largely unknown, and reliable tools are needed to distinguish fit from frail patients for treatment selection. Also, information regarding quality of life during and after treatment is scarce. PATIENTS AND METHODS: This multicenter NVALT25-ELDAPT (Dutch Association of Chest Physicians Trial Number 25 - Elderly with locally advanced Lung cancer: Deciding through geriatric Assessment on the oPtimal Treatment strategy) trial (NCT02284308) consists of a phase III randomized trial in combination with an observational study for all patients who do not participate in the randomized trial. The first aim of this study is to develop a reliable and clinically applicable screening tool to distinguish medically fit from frail patients. All patients ≥ 75 years diagnosed with stage III NSCLC are invited to undergo extensive geriatric assessment (part I). The second aim is to compare treatment tolerance, survival, and quality of life between concurrent and sequential chemoradiotherapy in fit patients (randomized trial, part II). For all patients, overall survival adjusted for quality of life (quality-adjusted survival) is described for each category of fitness and treatment strategy during and after treatment. CONCLUSION: With the results of the NVALT25-ELDAPT trial, treatment selection can be optimized and the best possible outcomes for each individual older patient with stage III NSCLC can be achieved.

Changes in treatment patterns and survival in elderly patients with stage I non-small-cell lung cancer with the introduction of stereotactic body radiotherapy and video-assisted thoracic surgery.

BACKGROUND: The optimal treatment of elderly patients with early-stage non-small-cell lung cancer (NSCLC) remains elusive. Still, the introduction of video-assisted thoracic surgery (VATS) and stereotactic body radiotherapy (SBRT) may have led to more elderly receiving treatment and improved median overall survival (OS). MATERIALS AND METHODS: We analysed data from the Netherlands Cancer Registry of 2168 patients ≥65 years with clinical stage I NSCLC and distinguished two periods: 2004-2008 (A) and 2009-2013 (B). The analyses focussed on treatment patterns and median OS for patients receiving surgery, radiotherapy or neither surgery nor radiotherapy. Furthermore, we explored the influence of the application of VATS and SBRT. RESULTS: The resection rate did not differ between the periods A and B (51% versus 53%; p = 0.37), despite significantly more VATS procedures in the latter period (0% versus 32%; p < 0.001). Application of radiotherapy increased (26% versus 33%; p = 0.001), especially SBRT (3% versus 63%; p < 0.001). The proportion of patients receiving neither therapy decreased (23% versus 14%; p < 0.001). Median OS for all patients significantly improved (31 versus 42 months; p = 0.001), and also for those receiving radiotherapy (23 versus 33 months; p = 0.02), but not significantly for surgical patients (65 versus 74 months; p = 0.16). Still, in multivariable analysis, surgical patients had an increased risk of death in period A compared with period B (hazard ratio [HR] 1.20; 95% confidence interval [CI], 1.01-1.43); this was not the case for patients receiving radiotherapy (HR 1.19; 95% CI, 0.99-1.43). Five-year OS was 57% for surgical patients and 23% for those receiving radiotherapy. CONCLUSION: In elderly patients with stage I NSCLC, the use of surgery remained constant, that of radiotherapy increased and fewer patients received neither treatment over the years. Median OS improved for all patients; surgery was associated with the highest long-term OS.

Geriatric Assessment for Older Patients with Non-small Cell Lung Cancer: Daily Practice of Centers Participating in the NVALT25-ELDAPT Trial.

INTRODUCTION: Geriatric assessment (GA) for older patients with lung cancer could provide insight into vulnerability, cognitive impairment, and risk of toxicity. Discontinuation and complications of intensive treatment could potentially be prevented in vulnerable and frail patients. This study aimed to evaluate current clinical practice of GA for older patients with lung cancer in the Netherlands and identify potential hurdles for implementation. METHODS: Pulmonologists and radiation oncologists participating in the NVALT25-ELDAPT trial completed an online questionnaire regarding current practice of GA, added value of GA for treatment decision-making and logistic barriers for patients with non-small cell lung cancer. RESULTS: 15 out of 17 centers responded. Three performed GA as standard procedure, three on indication, eight considered a frailty screening step before GA, and one did not perform GA. Suspicion of cognitive problems was mentioned most often as indication for GA and of added value for treatment decision-making, followed by older age, curative-intent treatment, and stage I-III lung cancer. Administered instruments for screening and extensive GA were diverse. Main barriers to implement GA in clinical practice were logistic problems (timescales and availability of trained personnel). CONCLUSION: The use of GA in clinical practice for patients with lung cancer varied widely across centers regarding instruments and domains. Physicians are uniform in their opinion about indications for GA and the added value for treatment decision-making. Research should focus on manageable instruments and important domains to assess for this heterogeneous group of older patients with lung cancer to optimize treatment selection. Trial registration The NVALT25-ELDAPT trial is registered under trial number NCT02284308. Details are available at http://www.eldapt.org (predominantly in Dutch).

Patterns of treatment and survival among older patients with stage III non-small cell lung cancer.

INTRODUCTION: Patterns of treatment and survival are largely unknown for older patients with stage III non-small cell lung cancer (NSCLC) in daily clinical practice. METHODS: All patients ≥65 years with stage III NSCLC (2009-2013) were included from the population-based Netherlands Cancer Registry. Descriptive and multivariable treatment and survival analyses were stratified for patients aged 65-74 years and ≥75 years. RESULTS: Compared to older patients (n = 3163), those aged 65-74 years (n = 3876) underwent more often surgery (21% vs 12% for stage IIIA), chemoradiotherapy (47% vs 22% for both stage IIIA and IIIB), and chemotherapy (23% vs 12% for stage IIIB), and received less radiotherapy (8% vs 22% for both stage IIIA and IIIB). One-year survival was significantly higher among patients aged 65-74 compared to those aged ≥75 (61% vs 43%, for stage IIIA and 45% vs 30% for stage IIIB; P < .01). However, stratification of treatment showed similar survival rates between age groups. Among patients aged 65-74 years, the multivariably adjusted hazard ratio (HR) of death was twice as high for patients receiving radiotherapy (HR 1.9 (95%CI 1.6-2.2) for stage IIIA and HR 2.5 (95%CI 2.1-3.0) for stage IIIB) and chemotherapy (HR 2.2 (95%CI 1.9-2.5) and HR 2.2 (95%CI 1.8-2.7), respectively) compared to chemoradiotherapy, and were slightly lower for patients aged ≥75 years receiving radiotherapy (HR 1.6 (95%CI 1.4-1.9) and HR 1.8 (95%CI 1.5-2.1), respectively) and chemotherapy (HR 2.2 (95%CI 1.8-2.7) and HR 1.8 (95%CI 1.5-2.2), respectively). Comorbidity was not significantly associated with poorer survival (p = .07). CONCLUSION: Chemoradiotherapy was more often applied among patients aged 65-74 years compared to those aged ≥75. While survival was worse for patients aged ≥75 years, differences between age groups largely disappeared after stratification for treatment. Future research should focus on predictive patient characteristics to distinguish patients within the heterogeneous older population who can benefit from curative-intent treatment.

Lung Cancer in the Oldest Old: A Nation-Wide Study in The Netherlands.

INTRODUCTION: An important step in improving research and care for the oldest patients with lung cancer is analyzing current data regarding diagnostic work-up, treatment choices, and survival. METHODS: We analyzed data on lung cancer from the Netherlands Cancer Registry (NCR-IKNL) regarding diagnostic work-up, treatment, and survival in different age categories; the oldest old (≥85 years of age) versus those aged 71-84 (elderly) and those aged ≤70 years (younger patients). RESULTS: 47,951 patients were included in the 2010-2014 NCR database. 2196 (5%) patients were aged ≥85 years. Histological diagnosis was obtained significantly less often in the oldest old (38%, p < 0.001), and less standard treatment regimen was given (8%, p < 0.001) compared to elderly and younger patients. 67% of the oldest old received best supportive care only versus 38% of the elderly and 20% of the younger patients (p < 0.001). For the oldest old receiving standard treatment, survival rates were similar in comparison with the elderly patients. In the oldest old, no survival differences were found when comparing standard or adjusted regimens for stage I and IV NSCLC; for stage III, oldest old receiving standard treatment had longer survival. No oldest old patients with stage II received standard treatment. CONCLUSION: Clinicians make limited use of diagnostics and invasive treatment in the oldest old; however, selected oldest old patients experienced similar survival rates as the elderly when receiving some form of anticancer therapy (standard or adjusted). More research is needed to further develop individualized treatment algorithms.

Stage III Non-Small Cell Lung Cancer in the elderly: Patient characteristics predictive for tolerance and survival of chemoradiation in daily clinical practice.

BACKGROUND: In unselected elderly with stage III Non-Small Cell Lung Cancer (NSCLC), evidence is scarce regarding motives and effects of treatment modalities. METHODS: Hospital-based multicenter retrospective study including unresectable stage III NSCLC patients aged ⩾70 and diagnosed between 2009 and 2013 (N=216). Treatment motives and tolerance (no unplanned hospitalizations and completion of treatment), and survival were derived from medical records and the Netherlands Cancer Registry. RESULTS: Patients received concurrent chemoradiation (cCHRT, 33%), sequential chemoradiation (sCHRT, 24%), radical radiotherapy (RT, 16%) or no curative treatment (27%). Comorbidity, performance status (58%) and patient refusal (15%) were the most common motives for omitting cCHRT. Treatment tolerance for cCHRT and sCHRT was worse in case of severe comorbidity (OR 6.2 (95%CI 1.6-24) and OR 6.4 (95%CI 1.8-22), respectively). One-year survival was 57%, 50%, 49% and 26% for cCHRT, sCHRT, RT and no curative treatment, respectively. Compared to cCHRT, survival was worse for no curative treatment (P=0.000), but not significantly worse for sCHRT and RT (P=0.38). CONCLUSION: Although relatively fit elderly were assigned to cCHRT, treatment tolerance was worse, especially for those with severe comorbidity. Survival seemed not significantly better as compared to sCHRT or RT. Prospective studies in this vital and understudied area are needed.