|Year : 2019 | Volume
| Issue : 1 | Page : 20-25
Exercise prehabilitation program for patients under neoadjuvant treatment for rectal cancer: A pilot study
Lidia B Alejo1, Itziar Pagola-Aldazabal1, Carmen Fiuza-Luces2, Daniel Huerga3, María Victoria de Torres4, Ana Soria Verdugo4, María Jesus Ortega Solano4, José Luis Felipe5, Alejandro Lucia1, Ana Ruiz-Casado6
1 School of Sports Sciences, European University of Madrid; Research in Physical Activity and Health, Research Institute “i+12” (12 Octubre University Hospital), Madrid, Spain
2 Research in Physical Activity and Health, Research Institute “i+12” (12 Octubre University Hospital), Madrid, Spain
3 Department of Surgery, Fuenlabrada University Hospital, Madrid, Spain
4 Department of Oncology, Fuenlabrada University Hospital, Madrid, Spain
5 School of Sports Sciences, European University of Madrid, Madrid, Spain
6 Department of Oncology, Puerta de Hierrro University Hospital, Majadahonda, Spain
|Date of Web Publication||13-Mar-2019|
Prof. Alejandro Lucia
European University of Madrid, 28670 Villaviciosa De Odón, Madrid
Source of Support: None, Conflict of Interest: None
Context: Prehabilitation is emerging as a method of preparing patients physically and mentally for the often disabling effects of cancer treatment.
Aims: This study aims to assess the feasibility and to explore the potential effects of a prehabilitation program consisting of educational physical exercise sessions in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy treatment (NCRT).
Settings and Design: This was a pilot study with 12 patients (3 males and 9 females, age 61 ± 7 years).
Subjects and Methods: The program included six educational sessions of exercise during NCRT. Adherence to the intervention; quality of life (QoL); anxiety and depression; body mass index; physical fitness (peak oxygen uptake (VO2peak), handgrip and dynamic leg strength); and physical activity (PA) levels were measured.
Statistical Analysis Used: Data are reported as the mean ± standard deviation or medians and interquartile ranges for questionnaire-derived data. Secondary outcome measures were compared using the nonparametric Wilcoxon test. The threshold P value for significance was calculated after correction for multiple comparisons using the Bonferroni method.
Results: Adherence to the program was 64 of 72 possible exercise education sessions completed, i.e., 89%. We detected a trend toward a significant improvement in VO2peak after the intervention (P = 0.015), together with reduced scores for both depression (P = 0.017) and the QoL domain “emotional function” (P = 0.027). Mean levels of moderate to vigorous PA tended to increase after the exercise program (P = 0.091).
Conclusions: Exercise might be an effective prehabilitation strategy for surgery during the period of NCRT.
Keywords: Oncology, physical activity, surgery
|How to cite this article:|
Alejo LB, Pagola-Aldazabal I, Fiuza-Luces C, Huerga D, de Torres MV, Verdugo AS, Ortega Solano MJ, Felipe JL, Lucia A, Ruiz-Casado A. Exercise prehabilitation program for patients under neoadjuvant treatment for rectal cancer: A pilot study. J Can Res Ther 2019;15:20-5
|How to cite this URL:|
Alejo LB, Pagola-Aldazabal I, Fiuza-Luces C, Huerga D, de Torres MV, Verdugo AS, Ortega Solano MJ, Felipe JL, Lucia A, Ruiz-Casado A. Exercise prehabilitation program for patients under neoadjuvant treatment for rectal cancer: A pilot study. J Can Res Ther [serial online] 2019 [cited 2019 May 20];15:20-5. Available from: http://www.cancerjournal.net/text.asp?2019/15/1/20/244450
| > Introduction|| |
Prehabilitation is emerging as a method of preparing patients both physically and mentally for the side effects of cancer treatment. Prehabilitation programs aim at improving an individual's functional capacity to confront an anticipated stressful situation such as surgery. In this context, the period of neoadjuvant chemoradiotherapy treatment (NCRT) represents an ideal scenario to assess the effects of an exercise prehabilitation intervention in cancer patients. Indeed, both the short duration of NCRT (~3 months in total, i.e., ~1.5 month, and thereafter, the surgery is delayed 6 weeks after the end of NCRT) and the emotional state of the patient make this period especially “teachable.” A low level of fitness, as assessed by cardiopulmonary exercise testing, has been associated with increased postoperative morbidity and more complications of anesthesia whereas prehabilitation can improve fitness and reduce perioperative risks. The present study assessed the feasibility and potential effects of a prehabilitation program consisting of educational physical exercise sessions in patients with rectal cancer undergoing NCRT. As the primary outcome, we targeted an adherence to the intervention of at least 60% and then examined the impact of the intervention on the patients' quality of life (QoL), psychological distress (anxiety and depression), body mass index (BMI), physical fitness, and physical activity (PA) level (secondary outcomes).
| > Subjects and Methods|| |
The study's inclusion criteria were signed informed consent, age ≥18 years, rectal adenocarcinoma Stage II–III, NCRT at the Hospital Universitario de Fuenlabrada (Madrid, Spain) and Eastern Cooperative Oncology Group performance status <3. Exclusion criteria were need for transfusions and psychoactive drug use. Among 23 eligible patients, 12 (3 males and 9 females, mean ± standard deviation [SD] age 61 ± 7 years (range: 50, 73)) accepted our invitation to participate in this study. The study protocol received local review board approval and adhered to the tenets of the Declaration of Helsinki.
Adherence to the intervention was determined by considering each individual session completed when participants successfully completed ≥90% of the prescribed exercises for the session.
These outcomes were determined twice in each participant, i.e., at baseline (before NCRT) and immediately before surgery [Figure 1].
|Figure 1: Study protocol indicating the different health professionals involved. NCRT=Neoadjuvant chemoradiotherapy, PA=Physical activity, QoL=Quality of life|
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Quality of life
Health-related QoL was determined using the European Organisation for Research and Treatment of Cancer (EORTC)-QoL questionnaire (QLQ) C-30.
Anxiety and depression
Patient psychological distress was assessed using the Hospital Anxiety and Depression Scale.
Body mass index
To calculate BMI, in kg/m2, body weight was determined to the nearest 0.05 kg using a balance scale (Ano Sayol SL, Barcelona, Spain) with participants in their underwear.
Cardiorespiratory fitness was assessed through peak oxygen uptake (VO2peak) determined in a one-mile walk according to the method described by Kline et al. Participants' handgrip strength was measured using a dynamometer (TKK 5001 Grip-D, Takei, Tokyo, Japan) and scores recorded in kilograms (to the nearest 0.1 kg). Participants also performed a 5-repetition sit-to-stand test on a straight-backed chair (40 cm high). For this test, the subject was instructed to sit down and stand up with arms folded across the chest as quickly as possible five times. The process was timed to the nearest 0.1 s from the initial sitting position to the final standing position at the end of the fifth stand using a stopwatch.
We objectively assessed spontaneous PA levels through accelerometry. Subjects were required to wear a triaxial Actigraph GT3X monitor device (Actigraph, Pensacola, FL, USA) for a minimum of 5 and maximum of 10 consecutive days including 2 weekend days. A minimum of 10 h of complete accelerometry data were recorded per day. For participants providing more than 5 consecutive days of recordings, only the data for the last 5 days including 2 weekend days were used. Predefined epoch and sample rate were 15 s and 30 Hz, respectively. Data were analyzed using ActiLife5 LITE software (Actigraph, Pensacola, FL, USA). Outcome variables were expressed as average intensity (counts/min) and counts were transformed into the time spent (average min/day and total min/week) engaged in either physical inactivity, light, moderate, or vigorous PA using the following cutoffs: inactivity <100 counts/min; light PA = 100–1951 counts/min; moderate PA = 1952–5724 counts/min (corresponding to 3–5.9 metabolic equivalents [METs], where 1 MET is equivalent to an oxygen consumption of 3.5 mL/kg/min); and vigorous PA ≥5725 counts/min (≥6 METs). The postintervention accelerometry assessment was done the week immediately after the end of the intervention.
All the participants attended six exercise education sessions described in detail in [Table 1]. Briefly, sessions included an introductory lecture, 5 practical classes on aerobic, resistance and flexibility outdoor exercises (conducted in a park), and a final overall session including all the above.
|Table 1: Physical exercise education sessions conducted with the patients at the Hospital de Fuenlabrada (Madrid, Spain) or nearby park|
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The Kolmogorov–Smirnov test was used to determine the normal distribution of the study variables. Data are reported as the mean ± SD or medians and interquartile ranges for questionnaire-derived data. Secondary outcome measures were compared before and after the intervention using the nonparametric Wilcoxon test. To minimize the risk of a Type I error, the threshold P value for significance was calculated after correction for multiple comparisons using the Bonferroni method, by dividing 0.05 by the total number of comparisons (=24), yielding P = 0.002.
| > Results|| |
Adherence to the program was calculated as 64 out of 72 possible exercise education sessions completed, i.e., 89%. Out of 12 participants enrolled, 10 participants completed all the sessions: one patient completed only 4 out of the 6 sessions due to adverse events provoked by radiotherapy, and another patient was unable to complete any of the sessions due to rapid disease progression. No adverse effects or events associated to the exercise sessions were noted.
The secondary outcome variables recorded in the participants are provided in [Table 2] and [Table 3]. VO2peak could not be determined in one patient because he was on treatment with beta-blockers. The preversus postintervention differences detected were a trend toward significant improvement in VO2peak after the intervention (P = 0.015–importantly, all participants showed higher values after the intervention [mean difference: 5.2 mL/kg/min, 95% confidence interval for the difference postminus preintervention = 1.0, 9.3]); and reduced scores for both depression (P = 0.017, again all participants improved in this outcome measure after the intervention) and the QoL domain “emotional function” (P = 0.027). Mean levels of moderate to vigorous PA (MVPA) also tended to increase after the exercise program (P = 0.091) and inactivity also tended to decrease (P = 0.091).
|Table 2: Psychosocial stress and quality of life before and after the exercise education intervention|
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|Table 3: Antropometry, fitness, and physical activity before and after the exercise education intervention|
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| > Discussion|| |
The preoperative period may be a better time than the postoperative period to implement such an intervention in patients undergoing colorectal resection for cancer. Recent evidence also indicates that exercise is safe and feasible in patients with breast cancer or locally advanced rectal cancer undergoing neoadjuvant treatment and surgery. Prehabilitation has been found beneficial in reducing the incidence of postoperative complications after intra-abdominal surgery. Prehabilitation could also serve to improve the physical condition of older patients preoperatively, including elderly patients with colorectal cancer.
The cancer prehabilitation exercise education program designed here is one of the first of its kind in Spain (with only one previously published study in this area) and also the first in general to involve exercise education. This was, however, a pilot study and further work is needed to increase our understanding of the possible benefits of this type of program in the treatment of rectal cancer. Our preliminary results corroborate those recently reported in a cohort of British patients undergoing NCRT before surgery for locally advanced rectal cancer. In the intervention arm of the latter trial (n = 22), 100% adherence to a 6-week structured responsive exercise training program was observed, and VO2peak was improved on average by 2.1 mL/kg/min (vs. 5.2 mL/kg/min observed here). The additions of our study to this pioneer study were the assessment of other important outcome measures, i.e., QoL, psychological distress (anxiety and depression) and levels of PA. Our adherence and VO2peak data together with the results of this recent research support the feasibility of an exercise prehabilitation program during NCRT. However, further work is needed to also establish the postsurgery consequences of this program. We propose studies addressing the impacts of prehabilitation on outcome variables such as mean hospital stay and conversion to open surgery. The improvement detected here in cardiorespiratory fitness expressed as VO2peak in all patients after only 6 exercise education sessions (over a period of 5 weeks) is striking, especially if we consider that VO2peak has been found to predict postoperative morbidity in a wide range of noncardiopulmonary surgical procedures. It should also be stressed that cardiorespiratory fitness assessed in the timed stair climb test seems to be a good predictor of perioperative complications in patients undergoing abdominal surgery. Further, in a recent study in patients scheduled to undergo colorectal surgery, meaningful benefits in cardiorespiratory fitness (assessed as walking capacity) were observed over several weeks (median = 38 weeks) of prehabilitation. However, such changes were not seen in all patients and 33% improved their walking capacity, 38% were within 20 m of their baseline capacity, and 29% deteriorated. Preintervention VO2peak in our participants averaged 24.4 mLO2/kg/min or ~7 (METs, where 1 MET is resting energy expenditure, i.e., ~3.5 mLO2/kg/min for the average person) and increased to 8.5 METs after the exercise education intervention lasting only 5 weeks. This finding deserves attention considering that in the absence of an exercise intervention, VO2peak tends to decrease from pre- to post-NRCT by 1.5 or ~2 mL/kg/min. Moreover, a VO2peak value below 8 METs is indicative of an increased risk of mortality and cardiovascular events in adult men and women (aged 40–60 years on average); cardiovascular disease being the leading cause of long-term morbidity and mortality among long-term cancer survivors. A VO2peak of <8 METs has been also associated with a more than 3-fold greater risk of digestive system cancer-related mortality. Although more research is needed, our results suggest that this type of prehabilitation programs might represent a viable strategy to prevent VO2peak decline during NRCT, and thus could provide a major benefit to the patients, notably by increasing their metabolic reserve and thus their ability to cope safely with a major stressor-like surgery.
Using the EORTC-QLQ30 QoL questionnaire, we recorded better preintervention scores to those reported for a Dutch cohort of rectal cancer patients and to reference scores reported for colorectal cancer. Such high QoL levels could be attributed, at least in some measure, to the high baseline MVPA levels of our patients (i.e., 332 min/week [Table 2], or double the minimum level recommended by the World Health Organization). In effect, there is evidence from a recent meta-analysis to suggest that regular exercise has a direct positive impact on QoL in patients with cancer in general, both during and following medical intervention. These high MVPA levels, nevertheless, do not necessarily imply a high VO2peak nor a healthy cardiometabolic profile in patients with cancer, as observed by in a cohort of survivors of cancer (mainly breast and colorectal) and could have a ceiling effect on further improvements in QoL.
The lack of a significant impact of the prehabilitation program on patient anxiety could be explained by the imminent nature of their surgery. Neither were any significant effects observed on BMI. We propose that future prehabilitation programs should be sufficiently ambitious to target a reduction in BMI. This is an important issue because mean BMI in the participants was >29 kg/m2, i.e., close to the obesity-threshold (=30 kg/m2); obesity having been identified to increase the conversion rate to open surgery and postoperative morbidity in rectal cancer. In contrast, we observed a tendency for depression to improve after the intervention.
A main limitation of our study was the lack of a control group, and its limited sample size owing to recruitment difficulties inherent to most exercise intervention studies. In addition, data on patients' lifestyle (e.g., smoking or dietary habits) should be taken into account as potential confounders in future research. Finally, the good results obtained could be the outcome of the very focused attention received by the participants which is not reproducible in usual collaborations with fitness specialists.
It is now clear that the optimal treatment for rectal cancer requires a multidisciplinary effort on the part of medical oncologists, radiotherapists, surgeons, pathologists, and nurses. Multimodal therapy together with advanced surgical techniques has led to a significant reduction in the incidence of local tumor recurrence. If it is confirmed that exercise is an effective prehabilitation strategy for surgery during the period of neoadjuvant treatment, this would provide further support for the idea that there is room for more players (e.g., fitness specialists) in the multidisciplinary approach to managing patients with rectal cancer.
We would like to acknowledge Ana Burton for her linguistic assistance.
Financial support and sponsorship
This study was financially supported by Foundation Real Madrid Chair 2099/07RM. €6,000.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]