Effects of a Pragmatic Home-based Exercise Program Concurrent With Neoadjuvant Therapy on Physical Function of Patients With Pancreatic Cancer: The PancFit Randomized Clinical Trial.

OBJECTIVE: To determine the effects of a preoperative, home-based exercise program on fitness and physical function in patients with pancreatic cancer. BACKGROUND: We previously established a well-tolerated preoperative exercise program after finding a high frequency of sarcopenia and frailty in patients with pancreatic cancer. METHODS: In this randomized, controlled trial (NCT03187951), patients with pancreatic cancer were randomized to Arm A: enhanced usual care or Arm B: prescribed aerobic and resistance exercise during neoadjuvant therapy. Patients received nutrition counseling and activity trackers. The primary endpoint was a 6-minute walk distance (6MWD; ≥14 meters improvement was clinically meaningful). Secondary endpoints included additional physical function tests, health-related quality of life, and clinical outcomes. RESULTS: One hundred fifty-one patients were randomized. Objectively measured weekly activity (153.2±135.6 and 159.8±122.8 min in Arm A and B, respectively, P =0.62) and self-reported weekly moderate-to-strenuous physical activity (107.4±160.4 and 129.6±161.6 min in Arm A and Arm B, respectively, P =0.49) were similar, but weekly strength training sessions increased more in Arm B (by 1.8±1.8 vs 0.1±2.4 sessions, P <0.001). 6MWD improved in both Arm A (mean change 18.6±56.8 m, P =0.01) and Arm B (27.3±68.1 m, P =0.002). Quality of life and clinical outcomes did not significantly differ between arms. Pooling patients in both study groups, exercise, and physical activity was favorably associated with physical performance and clinical outcomes. CONCLUSIONS: In this randomized trial of prescribed exercise versus enhanced usual care during neoadjuvant therapy for pancreatic cancer, a high volume of physical activity and increased exercise capacity were observed in both arms, highlighting the importance of activity among patients preparing for surgery.

The Role of Home-Based Exercise in Maintaining Skeletal Muscle During Preoperative Pancreatic Cancer Treatment.

Loss of skeletal muscle and inferior muscle quality are associated with poor prognosis in patients undergoing preoperative treatment for pancreatic cancer, so maintaining skeletal muscle health before surgery may help accelerate patients' functional recovery and improve their quality of life following surgery. While exercise helps maintain or increase skeletal muscle in individuals undergoing cancer treatment, its efficacy during pancreatic cancer treatment is unclear. Accordingly, in this study we compared changes in skeletal muscle quantity (skeletal muscle index [SMI]) and quality (skeletal muscle density [SMD]) during preoperative pancreatic cancer treatment in participants in a home-based exercise program (EP) and a historical cohort of patients who received the usual care (UC) with no formal exercise programming. Recommendations for the EP cohort included both aerobic and resistance exercise. We assessed changes in SMI and SMD using computed tomography scans administered at treatment planning (T0, prior to EP enrollment) and preoperative restaging (T1) for 33 EP and 64 UC patients and compared changes between groups. The UC patients had statistically significant SMI decreases from T0 to T1 (-1.4 ± 3.8 cm2/m2; p = .005), while the EP patients did not (0.2 ± 3.2 cm2/m2; p = .7). The SMI loss was significantly worse for the UC than for the EP patients (p = .03). Neither group demonstrated statistically significant changes in SMD from T0 to T1, nor did the groups differ in the amount of change in SMD. An adjusted linear regression model demonstrated that EP participation was significantly associated with better SMI maintenance (p = .02). These results suggest that participation in a home-based EP during preoperative treatment may help improve skeletal muscle health and clinical and quality of life outcomes for pancreatic cancer survivors.

Home-Based Exercise Prehabilitation During Preoperative Treatment for Pancreatic Cancer Is Associated With Improvement in Physical Function and Quality of Life.

Purpose: To investigate relationships among physical activity, changes in physical function, and health-related quality of life (HRQOL) among patients with pancreatic adenocarcinoma enrolled in a home-based exercise prehabilitation program. Methods: Patients with resectable pancreatic adenocarcinoma receiving preoperative chemotherapy and/or chemoradiation were enrolled on this prospective, single-arm trial and were advised to perform ≥60 minutes each of moderate-intensity aerobic exercise and strengthening exercise weekly. Activity was measured via self-report and accelerometers, including moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), and sedentary activity (SA). Physical function measures at baseline and restaging follow-up included 6-minute walk test (6MWT), 5 times sit-to-stand (5×STS), handgrip strength (HGS), 3-m walk for gait speed (GS), and the PROMIS Physical Function Short Form. HRQOL was measured via the FACT-Hep questionnaire. Results: Fifty participants with mean age 66 years (standard deviation = 8 years) were enrolled. The 6MWT, 5×STS, and GS significantly improved from baseline to restaging follow-up (P=.001, P=.049, and P=.009, respectively). Increases in self-reported aerobic exercise, weekly MVPA, and LPA were associated with improvement in 6MWT (ß=.19, P=.048; ß=.18, P=.03; and ß=.08, P=.03, respectively) and self-reported physical functioning (ß=.02, P=.03; ß=.03, P=.005; and ß=.01, P=.02, respectively). Increased weekly LPA was associated with increased HRQOL (ß=.03, P=.02). Increased SA was associated with decreased HRQOL (ß=-.02,P=.01). Conclusions: Patients with potentially resectable pancreatic cancer exhibit meaningful improvement in physical function with prehabilitation; physical activity was associated with improved physical function and HRQOL. These data highlight the importance of physical activity during treatment for pancreatic cancer.

Supports and Barriers to Home-Based Physical Activity During Preoperative Treatment of Pancreatic Cancer: A Mixed-Methods Study.

BACKGROUND: Physical activity and exercise appear to benefit patients receiving preoperative treatment for cancer. Supports and barriers must be considered to increase compliance with home-based exercise prescriptions in this setting. Such influences have not been previously examined. METHODS: The authors used quantitative and qualitative methods to examine potential physical activity influences among patients who were prescribed home-based aerobic and strengthening exercises concurrent with preoperative chemotherapy or chemoradiation for pancreatic cancer. Physical activity was measured using exercise logs and accelerometers. Social support for exercise and perceived neighborhood walkability were measured using validated surveys. Relationships between influences and physical activity were evaluated using linear regression analyses and qualitative interviews. RESULTS: Fifty patients received treatment for a mean of 16 (9) weeks prior to planned surgical resection. Social support from friends and neighborhood esthetics were positively associated with physical activity (P < .05). In interviews, patients confirmed the importance of these influences and cited encouragement from health care providers and desire to complete and recover from treatment as additional motivators. CONCLUSIONS: Interpersonal and environmental motivators of exercise and physical activity must be considered in the design of future home-based exercise interventions designed for patients receiving preoperative therapy for cancer.

Association between frailty syndrome and survival in patients with pancreatic adenocarcinoma.

BACKGROUND: Frailty is a syndrome characterized by weakness, slow gait, weight loss, exhaustion, and low activity. We sought to determine whether frailty was associated with age or stage in newly diagnosed patients with pancreatic ductal adenocarcinoma (PDAC), and determine its association with survival. METHODS: Consecutive patients with newly diagnosed PDAC of all stages underwent baseline assessment. Frailty (per Fried criteria) was defined as having three or more abnormalities in: grip strength, gait speed, weight loss, self-reported exhaustion, or self-reported physical activity. Baseline clinicodemographic characteristics, anatomic stage, performance status, and laboratory markers of prognosis were included. The association between baseline characteristics, frailty, and survival was determined. The associations of individual frailty measures with age, stage, comorbidities, and performance status were examined. Body composition was measured from computed tomographic images using SliceOMatic software. RESULTS: Of 150 patients enrolled, 8 were excluded because they did not have PDAC on final diagnosis. The median age was 65 years (range, 32-89). Seventy-nine patients (55.6%) were sarcopenic, and 36 (25.4%) were frail. Frailty was associated with increasing comorbidities (P = 0.03) and worse performance status (P < 0.01). During follow-up, 79 patients (56%) died. Frailty was significantly associated with death during the follow-up period (P < 0.001) for the entire cohort, including patients with curative (P = 0.038) and palliative (P = 0.003) treatment plans. CONCLUSIONS: Frailty was seen frequently in patients with newly diagnosed PDAC and was not associated with increasing age or more advanced stage. Frailty was a predictor of survival, including patients treated with curative intent.

Pancreas Cancer-Associated Weight Loss.

Unintentional weight loss in patients with pancreatic cancer is highly prevalent and contributes to low therapeutic tolerance, reduced quality of life, and overall mortality. Weight loss in pancreatic cancer can be due to anorexia, malabsorption, and/or cachexia. Proper supportive care can stabilize or reverse weight loss in patients and improve outcomes. We review the literature on supportive care relevant to pancreatic cancer patients, and offer evidence-based recommendations that include expert nutritional assessment, counseling, supportive measures to ensure adequate caloric intake, pancreatic enzyme supplementation, nutritional supplement replacement, orexigenic agents, and exercise. Pancreatic Cancer Action Network-supported initiatives will spearhead the dissemination and adoption of these best supportive care practices. IMPLICATIONS FOR PRACTICE: Weight loss in pancreatic cancer patients is endemic, as 85% of pancreatic cancer patients meet the classic definition of cancer cachexia. Despite its significant prevalence and associated morbidity, there is no established approach to this disease entity. It is believed that this is due to an important knowledge gap in understanding the underlying biology and lack of optimal treatment approaches. This article reviews the literature regarding pancreas cancer-associated weight loss and establishes a new framework from which to view this complex clinical problem. An improved approach and understanding will help educate clinicians, improve clinical care, and provide more clarity for future clinical investigation.

Physical activity and exercise during preoperative pancreatic cancer treatment.

PURPOSE: Guidelines recommend exercise to cancer survivors, but limited data exists regarding exercise among patients undergoing preoperative cancer treatment. We examined differences in weekly self-reported exercise and accelerometer-measured physical activity among participants in a home-based exercise program administered during preoperative treatment for pancreatic cancer. METHODS: Participants were encouraged to perform at least 60 min/week of moderate-intensity aerobic exercise and at least 60 min/week of full-body strengthening exercises concurrent with chemotherapy, chemoradiation therapy or both sequentially and received resistance equipment, program instruction, and biweekly follow-up calls to encourage adherence. Self-reported aerobic and strengthening exercise minutes were measured using daily logs, and physical activity was measured objectively using accelerometers. RESULTS: Fifty participants (48% female, mean age 66 ± 8 years) participated for an average of 16 ± 9 preoperative weeks. Participants reported overall means of 126 ± 83 weekly minutes of aerobic exercise and 39 ± 33 weekly minutes of strengthening exercise in daily logs. Participants performed 158.7 ± 146.7 weekly minutes of accelerometer-measured moderate-to-vigorous physical activity. There were no significant differences in exercise or physical activity between treatment phases. CONCLUSIONS: These findings suggest that it is feasible to target the entire preoperative course for exercise prescription. Although participants exceeded aerobic exercise recommendations on average, we observed low strengthening exercise adherence and wide variability in self-reported exercise and accelerometer physical activity variables. These findings suggest that additional support, including program adaptations, may be necessary to overcome barriers to exercise or improve motivation when prescribing exercise in this clinical scenario.

Anthropometric Changes in Patients with Pancreatic Cancer Undergoing Preoperative Therapy and Pancreatoduodenectomy.

BACKGROUND: The changes in body composition that occur in response to therapy for localized pancreatic ductal adenocarcinoma (PDAC) and during the early survivorship period, as well as their clinical significance, are poorly understood. METHODS: One hundred twenty-seven consecutive patients with PDAC who received preoperative therapy followed by pancreatoduodenectomy (PD) at a single institution between 2009 and 2012 were longitudinally evaluated. Changes in skeletal muscle (SKM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were measured on serial computed tomography images obtained upon presentation, prior to pancreatectomy, and approximately 3 and 12 months after surgery. RESULTS: Prior to therapy, patients' mean baseline BMI was 26.5 ± 4.7 kg/m2 and 63.0% met radiographic criteria for sarcopenia. During a mean 5.4 ± 2.3 months of preoperative therapy, minimal changes in SKM (- 0.5 ± 7.8%, p > 0.05), VAT (- 1.8 ± 62.6%, p < 0.001), and SAT (- 4.8 ± 27.7%, p < 0.001) were observed. In contrast, clinically significant changes were observed on postoperative CT compared to baseline anthropometry: SKM - 4.1 ± 10.7%, VAT - 38.7 ± 30.2%, and SAT - 24.1 ± 22.6% (all p < 0.001) and these changes persisted at one year following PD. While anthropometric changes during preoperative therapy were not independently associated with survival, SKM gain between the postoperative period and one-year follow-up was associated with improved overall survival (OR 0.50, 95% CI 0.29-0.87). CONCLUSIONS: In contrast to the minor changes that occur during preoperative therapy for PDAC, significant losses in key anthropometric parameters tend to occur over the first year following PD. Ongoing SKM loss in the postoperative period may represent an early marker for worse outcomes.

Symptom Management and Palliative Care in Pancreatic Cancer.

Evidence documents the benefits of palliative care to ameliorate the symptoms of pancreatic cancer as well as those from its treatment. Professional organizations now recommend palliative care for all patients with pancreatic cancer early in the course of illness and concurrently with active treatment. Scrupulous symptom management as well as sensitive communication and advance care planning allow oncologists to provide "primary palliative care" and to care well for patients with pancreatic cancer throughout the course of their illness.

Nutrition Implications for Long-Term Survivors of Pancreatic Cancer Surgery [Formula: see text].

With slowly increasing survival rates in pancreatic cancer and international consensus guidelines recommending surgical resection of premalignant lesions, survival post-pancreatic resection is increasing. With longer survival time, the significant comorbidities of such major surgery have far-reaching effects on the nutrition status of the survivor of pancreatic cancer. This review describes the many nutrition-related side effects of pancreatic surgery, including the development of pancreatic enzyme insufficiency, micronutrient deficiencies, diabetes, fatty liver, and metabolic bone disease. Beyond causing additional medical problems, each of these can have significant effects on quality of life and functional status. The potential mechanisms, diagnosis criteria, and potential treatments of these conditions are described. Overall, little literature exists to fully describe the effects of these comorbidities, and even less is able to guide effective treatments for this population. Clinicians caring for these patients should begin incorporating goals for promotion of long-term health and reduction of these known and reported comorbidities in patients who have undergone pancreatic surgery. Treatment plans in this population remain understudied, and clinicians may need to consider recommendations for similar disease states when developing interventions for these patients.