Lifestyle and Subsequent Malignant Neoplasms in Childhood Cancer Survivors: A Report from the St. Jude Lifetime Cohort Study.

INTRODUCTION: This study aimed to assess longitudinal associations between lifestyle and subsequent malignant neoplasms (SMNs) in young adult childhood cancer survivors. METHODS: Members of the St. Jude Lifetime Cohort (SJLIFE) aged ≥18 years and surviving ≥5 years after childhood cancer diagnosis were queried and evaluated for physical activity, cardiorespiratory fitness (CRF), muscle strength, body mass index (BMI), smoking, risky drinking, and a combined lifestyle score. Time to first SMN, excluding nonmalignant neoplasms and nonmelanoma skin cancer, was the outcome of longitudinal analysis. RESULTS: Survivors (n = 4072, 47% female, 29% smokers, 37% risky drinkers, 34% obese, and 48% physically inactive) had a mean (SD) time between baseline evaluation and follow-up of 7.0 (3.3) years, an age of 8.7 (5.7) years at diagnosis, and an age of 30 (8.4) years at baseline lifestyle assessment. Neither individual lifestyle factors nor a healthy lifestyle score (RR 0.8, 0.4-1.3, p = 0.36) were associated with the risk of developing an SMN. CONCLUSIONS: We did not identify any association between lifestyle factors and the risk of SMN in young adult childhood cancer survivors.

Movement efficiency in survivors of childhood acute lymphoblastic leukemia: a report from the St. Jude lifetime cohort study.

PURPOSE: Movement efficiency, a measure of neuromuscular biomechanics, may be modified by physical activity. We aimed to assess the risk of and risk factors for low movement efficiency in survivors of childhood acute lymphoblastic leukemia (ALL). METHODS: Participants underwent an assessment of activity energy expenditure (AEE) with actigraphy, and the gold standard doubly labeled water, where the differences between elimination rates of oxygen and hydrogen from body water are evaluated over a week. Movement efficiency was assessed using the raw residuals of a linear regression between AEEs from accelerometers and doubly labeled water. Elastic-net logistic regressions were used to identify demographic, treatment, and functional variables associated with movement efficiency. RESULTS: The study cohort included 256 non-cancer controls and 302 ALL survivors (48% female), categorized as efficient (N = 24), normal (N = 245), or inefficient (N = 33) based on their movement efficiency. There was no difference in the odds for poor movement efficiency between survivors (n = 33, 10.9%) compared to controls (n = 23, 9.0%, odds ratio [OR]: 1.19, 95% confidence interval [CI]: 0.67, 2.10; p = 0.55). In survivors, neuropathy was associated with a higher risk of being inefficient compared to efficient (OR 4.30, 95% CI 1.03-17.96), while obesity (≥ 30 kg/m2) had a protective association (OR 0.18, 95% CI 0.04-0.87). CONCLUSIONS: Neuropathy was associated with a higher risk of poor movement efficiency in survivors of childhood ALL. IMPLICATIONS FOR CANCER SURVIVORS: These results further highlight impairments associated with treatment-induced neuropathy in survivors of childhood ALL.

Long-term results of a short-term home-based pre- and postoperative exercise intervention on physical recovery after colorectal cancer surgery (PHYSSURG-C): a randomized clinical trial.

AIM: The aim of this work was to assess the effect of a short-term, home-based exercise intervention before and after colorectal cancer surgery on 12-month physical recovery within a previously reported randomized control trial (RCT). METHOD: PHYSSURG-C is an RCT in six participating hospitals in Sweden. Patients aged ≥20 years planned for elective colorectal cancer surgery were eligible. The intervention consisted of unsupervised moderate-intensity physical activity 2 weeks preoperatively and 4 weeks postoperatively. Usual care was control. The primary outcome measure in PHYSSURG-C was self-assessed physical recovery 4 weeks postoperatively. The predefined long-term follow-up outcomes included: self-assessed physical recovery 12 months postoperatively and reoperations and readmissions 91-365 days postoperatively. The statistical models were adjusted with tumour site (colon or rectum), neoadjuvant therapy (none, radiotherapy or chemo/radiotherapy) and type of surgery (open or laparoscopic). RESULTS: A total of 616 participants were available for the 12-month follow-up. Groups were balanced at baseline regarding demographic and treatment variables. There was no effect from the intervention on self-reported physical recovery [adjusted odds ratio (OR) 0.91, p = 0.60], the risk of reoperation (OR 0.97, p = 0.91) or readmission (OR 0.88, p = 0.58). CONCLUSION: The pre- and postoperative unsupervised moderate-intensity exercise intervention had no effect on long-term physical recovery after elective colorectal cancer surgery. There is still not enough evidence to support clinical guidelines on preoperative exercise to improve outcome after colorectal cancer surgery.

Lifestyle and subsequent meningioma in childhood cancer survivors: A report from the St. Jude Lifetime Cohort study.

BACKGROUND: Lifestyle is associated with meningioma risk in the general population. AIMS: We assessed longitudinal associations between lifestyle-associated factors and subsequent meningiomas in childhood cancer survivors. METHODS AND RESULTS: Childhood cancer survivors age ≥18 years in the St. Jude Lifetime Cohort Study were evaluated for body composition, self-reported physical activity, cardiopulmonary fitness, muscle strength, smoking, and alcohol consumption at baseline. Time to first meningioma analyses were performed, adjusted for sex, age at diagnosis and baseline assessment, treatment decade, and childhood cancer treatment exposures. The study included 4,072 survivors (47% female; [mean (SD)] 9 (6) years at diagnosis; 30 (8.5) years at the start of follow-up, with 7.0 (3.3) years of follow-up). 30% of the participants were survivors of acute lymphoblastic leukemia and 29% of the participants had received cranial radiation. During follow-up, 90 participants developed ≥1 meningioma, of whom 73% were survivors of acute lymphoblastic leukemia, with cranial radiation being the strongest risk factor (relative risk [RR] 29.7, 95% confidence interval [CI] 10.6-83.2). Muscle strength assessed by knee extension was associated with a lower risk of developing a meningioma in the adjusted analyses (RR 0.5, 95% CI 0.2-1.0, p = 0.04 for quartiles 3-4 vs. 1). No other lifestyle-associated variable was associated with subsequent meningioma. CONCLUSION: Independent of cranial radiation, muscle strength was associated with a lower risk of developing a subsequent meningioma in childhood cancer survivors.

Associations between BMI in youth and site-specific cancer in men-A cohort study with register linkage.

OBJECTIVE: This study examined BMI in young men and incident site-specific cancer to estimate population attributable fractions due to BMI based on projected obesity prevalence. METHODS: A population-based cohort study with measured height and weight at age 18. Cox regression models assessed linear associations for BMI and included age, year, and site of conscription as well as parental level of education as covariates. RESULTS: Primary analyses were performed in 1,489,115 men, of whom 78,217 subsequently developed cancer during a mean follow-up of 31 years. BMI was linearly associated with risk of developing all 18 site-specific cancers assessed (malignant melanoma; leukemia; myeloma; Hodgkin lymphoma; non-Hodgkin lymphoma; and cancer in the lungs, head and neck, central nervous system, thyroid, esophagus, stomach, pancreas, liver and gallbladder, colon, rectum, kidney, and bladder), in some instances evident at BMI levels usually defined as normal (20-25 kg/m2 ). Higher BMI was associated with lower risk of prostate cancer. The highest hazard ratios and population attributable fractions were seen for some gastrointestinal cancers. CONCLUSIONS: This study reports linear associations between BMI at age 18 and subsequent site-specific cancers, calling for rapid action to stem the obesity epidemic and to prepare the health care system for steep increases in cancer cases.

Cardiorespiratory fitness and BMI measured in youth and 5-year mortality after site-specific cancer diagnoses in men-A population-based cohort study with register linkage.

BACKGROUND: Our aim was to assess associations between cardiorespiratory fitness (CRF) and body mass index (BMI) in youth and 5-year mortality after site-specific cancer diagnoses in men. METHODS: Men with cancer from a population who underwent military conscription at ages 16-25 during 1968-2005 in Sweden were included. CRF was assessed as maximal aerobic workload on a cycle ergometer test and was classified as low, moderate, or high. BMI (kg/m2 ) was classified as underweight (<18.5), normal weight (18.5-24.9), overweight (25-29.9), or obesity (>30). Conscription data were linked with register data on cancer diagnosis and mortality. Analyses included CRF, BMI, date of diagnosis, and age, year, and center for conscription. RESULTS: A total of 84,621 cancer cases were included. Mean age at diagnosis was 52 years. Follow-up data were available during a mean of 6.5 years. There were linear protective associations between CRF and mortality after any cancer diagnosis (hazard ratio [HR] for high vs. low CRF 0.70), malignant skin cancer (HR 0.80), non-Hodgkin lymphoma (HR 0.78), and cancer in the lungs (HR 0.80), head and neck (HR 0.68), pancreas (HR 0.83), stomach (HR 0.78), liver (HR 0.84), rectum (HR 0.79), and bladder (HR 0.71). Overweight and/or obesity were associated with increased mortality after any cancer (HR for obesity vs. normal weight 1.89), malignant skin cancer (HR 2.03), Hodgkin lymphoma (HR 2.86) and cancer in the head and neck (HR 1.38), thyroid (HR 3.04), rectum (HR 1.53), kidney (HR 1.90), bladder (HR 2.10), and prostate (HR 2.44). CONCLUSION: We report dose-dependent associations between CRF and BMI in youth and mortality after site-specific cancer diagnoses in men. The associations with mortality could be due to both cancer inhibition and an improved tolerance to withstand cancer treatment. These results strengthen the incentive for public health efforts aimed at establishing a high CRF and normal weight in youth.

Associations between cardiorespiratory fitness in youth and the incidence of site-specific cancer in men: a cohort study with register linkage.

OBJECTIVES: To assess the associations between cardiorespiratory fitness (CRF) in young men and the incidence of site-specific cancer. METHODS: A Swedish population-based cohort study with register linkage of men who underwent military conscription in 1968-2005 was undertaken. CRF was assessed by maximal aerobic workload cycle test at conscription. Cox regression models assessed linear associations and included CRF, age, year and site of conscription, body mass index and parental level of education. CRF was also categorised into low, moderate and high for facilitated interpretation and results comparing high and low CRF are reported. RESULTS: Primary analyses were performed in 1 078 000 men, of whom 84 117 subsequently developed cancer in at least one site during a mean follow-up of 33 years. Higher CRF was linearly associated with a lower hazard ratio (HR) of developing cancer in the head and neck (n=2738, HR 0.81, 95% CI 0.74 to 0.90), oesophagus (n=689, HR 0.61, 95% CI 0.50 to 0.74), stomach (n=902, HR 0.79, 95% CI 0.67 to 0.94), pancreas (n=1280, HR 0.88, 95% CI 0.76 to 1.01), liver (n=1111, HR 0.60, 95% CI 0.51 to 0.71), colon (n=3222, HR 0.82, 95% CI 0.75 to 0.90), rectum (n=2337, HR 0.95, 95% CI 0.85 to 1.05), kidney (n=1753, HR 0.80, 95% CI 0.70 to 0.90) and lung (n=1635, HR 0.58, 95% CI 0.51 to 0.66). However, higher CRF predicted a higher hazard of being diagnosed with prostate cancer (n=14 232, HR 1.07, 95% CI 1.03 to 1.12) and malignant skin cancer (n=23 064, HR 1.31, 95% CI 1.27 to 1.36). CONCLUSION: We report a number of protective associations between higher CRF in healthy young men and the subsequent hazard of site-specific cancers. These results have implications for public health policymaking, strengthening the incentive to promote health through improving CRF in youth.

Survival in relation to time to start of curative treatment of colon cancer: A national register-based observational noninferiority study.

AIM: There are ample discussions regarding the timing of treatment, especially in the era after Covid that caused delay to treatment. The aim of this study was to determine whether a delayed start to curative treatment, within 29-56 days after a diagnosis of colon cancer, was noninferior to starting treatment within 28 days, with regard to all-cause mortality. METHOD: This is a national register-based observational noninferiority study, with a noninferiority margin of hazard ratio (HR) 1.1, including all patients treated with curative intent for colon cancer in Sweden between 2008 and 2016. The primary outcome was all-cause mortality. Secondary outcomes were length of hospital stay, readmissions and reoperations within 1 year after surgery. Exclusion criteria were emergency surgery, disseminated disease at diagnosis, missing diagnosis date and treatment for another cancer 5 years before colon cancer diagnosis. RESULTS: A total of 20 836 individuals were included. A period of 29-56 days from diagnosis to start of curative treatment was noninferior versus starting treatment within 28 days for the primary outcome of all-cause mortality (HR 0.95, 95% CI 0.89-1.00). Starting treatment within 29-56 days was associated with a shorter length of stay (average 9.2 vs. 10 days) but a higher risk of reoperation compared to within 28 days. Post hoc analyses demonstrated that surgical modality was driving survival rather than time to treatment. Overall survival was greater after laparoscopic surgery (HR 0.78, 95% CI 0.69-0.88). CONCLUSION: For patients with colon cancer, a period of up to 56 days from diagnosis to the start of curative treatment did not lead to worse overall survival.

The effect of nonsupervised physical activity before and after breast cancer surgery on quality of life: Results from a randomized controlled trial (PhysSURG-B).

BACKGROUND AND OBJECTIVE: The PhysSURG-B trial of prehabilitation before breast cancer surgery randomized patients to a nonsupervised physical activity or a control group. The effects of the intervention on short- and long-term quality of life (QoL) were examined, with a subgroup analysis of patients receiving adjuvant chemotherapy. METHODS: Female patients planned for surgery were randomly assigned to either an intervention of 30 min of self-administered physical aerobic activity daily 2 weeks before and 4 weeks after surgery or control. QoL was assessed with questionnaires at baseline, 4 weeks and 12 months postoperatively using the instruments FACT-B, RAND-36, and EQ-VAS. RESULTS: Of 354 included participants at 12 months after surgery, 287 were available for analysis. FACT- B scores at 4 weeks and 12 months showed no differences between intervention compared to control, odds ratio (OR) of 0.975 (95% confidence interval (CI) 0.636-1.495) and 0.883 (95% CI 0.581-1.342), respectively. There was no difference in EQ-VAS comparing intervention to control at 4 weeks and 12 months, respectively, OR 1.163 (95% CI 0.760-1.779) and 0.817 (95% CI 0.559-1.300). RAND-36 domains "role limitations due to physical health" and "pain" showed a decrease at 4 weeks in both groups, returning toward baseline at 12 months follow-up. The subgroup who received adjuvant chemotherapy had significantly lower QoL measured using FACT-B at 12 months compared to patients not receiving chemotherapy (OR 0.475; 95% CI 0.300-0.753). CONCLUSIONS: An intervention of non-supervised physical activity before and after surgery for breast cancer showed no effect on short or long-term QoL, compared to control. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT02560662.

[Physical activity supports cardiovascular fitness and muscle strength and has positive effects on quality of life among cancer survivors]. / Rekommendation om träning vid cancer kan förbättra livskvalitet.

Enhanced screening and efficient cancer treatments have led to a growing number of cancer survivors. In Sweden over 500 000 individuals have or have had cancer [1]. Cancer survivors can experience a wide range of disease and treatment related symptoms, that profoundly affect their health related quality of life. For example, women treated for breast cancer have on average 25 percent lower physical fitness compared to women without a cancer diagnosis. Recent evidence suggests that exercise has a positive effect on physical fitness, muscle strength, cancer related fatigue and quality of life among cancer survivors. An effective exercise prescription for health related outcomes in adult cancer survivors includes aerobic training at a moderate intensity for a total of 150 minutes per week. Adding resistance training two times per week has additional effects on muscle strength and physical functioning. Supervised exercise programs seem to be more effective than unsupervised or home based programs.

Effect of Short-term Homebased Pre- and Postoperative Exercise on Recovery After Colorectal Cancer Surgery (PHYSSURG-C): A Randomized Clinical Trial.

OBJECTIVE: To determine the effect of a short-term, unsupervised exercise intervention before and after colorectal cancer surgery on self-assessed physical recovery. SUMMARY OF BACKGROUND DATA: Preoperative exercise interventions could help improve recovery after colorectal cancer surgery and is currently recommended. METHODS: A randomized, parallel, open-label trial in six university or regional hospitals in Sweden. Inclusion criteria were age ≥20 years and planned elective colorectal cancer surgery. Participants were randomized to either a physical activity intervention with aerobic activity and inspiratory muscle training 2 weeks pre- and 4 weeks postoperatively or usual care. The primary outcome measure was self-assessed physical recovery 4 weeks postoperatively. Analyses were performed according to intention to treat. Outcome assessors were masked regarding the intervention while both participants and physiotherapists were informed due to the nature of the intervention. RESULTS: Between January 22, 2015, and May 28, 2020, 761 participants were recruited and assigned to either intervention (I) (n = 379) or control (C) (n = 382). After exclusions 668 participants (I = 317, C = 351) were included in the primary analysis. There was no effect from the intervention on the primary outcome measure (adjusted odds ratio 0.84, 95% confidence interval 0.62-1.15) with 13% and 15% of participants feeling fully physically recovered in I and C, respectively. There were no reported adverse events. CONCLUSIONS: There was no effect from a physical activity intervention before and after colorectal cancer surgery on short-term self-assessed physical recovery. The results from this study call for reconsiderations regarding current recommendations for preoperative physical activity interventions.

Association between self-assessed preoperative level of physical activity and postoperative complications - An observational cohort analysis within a randomized controlled trial (PHYSSURG-C).

INTRODUCTION: Physical activity has been suggested as a modifiable risk factor for postoperative recovery after major surgery. We aimed to further define the association between self-reported leisure time physical activity and postoperative complications and recovery on a group level. MATERIALS AND METHODS: An observational cohort analysis was performed within a randomized controlled trial. Patients ≥20 years with colorectal cancer were eligible. Between January 2015 and May 2020, 761 participants were recruited. Leisure time physical activity was self-assessed on a four-grade scale. The primary outcome in this analysis was postoperative complications within 90 days, measured with the comprehensive complication index (CCI). Secondary outcomes were CCI for the index hospital stay, CCI 30 days postoperatively, specific types of complications, length of hospital stay, and self-assessed physical recovery. Analyses were adjusted for gender, age, study center, alcohol consumption, tumor stage, colon/rectal cancer, neoadjuvant therapy, and open or laparoscopic surgery. RESULTS: Data on preoperative physical activity was available for 614 participants. Participants who reported some physical activity had on average a lower CCI 90 days postoperatively than sedentary participants (odds ratio 0.63, 95% CI 0.43-0.92). Similar patterns were shown for complications during hospital stay and within 30 days. There were trends towards lower risk for several types of complications, reoperations and length of hospital stay but the only difference shown was for respiratory insufficiency. CONCLUSION: Physically active participants experienced fewer postoperative complications, which suggests the information has a potential prognostic value. The work for increasing physical activity in the general population should continue.

Effects of a home-based exercise program on the insulin-like growth factor axis in patients operated for colorectal cancer in Sweden: Results from the randomised controlled trial PHYSSURG-C.

OBJECTIVES: We report results from a subgroup within the ongoing PHYSSURG-C trial with the aim to examine effects of exercise on IGF-1 and IGFBP-3 in patients undergoing colorectal cancer surgery. DESIGN: Randomised controlled trial. SETTING: A Swedish university hospital. PARTICIPANTS: Between 2015 and 2016, 217 patients were enrolled (I = 106, C = 111), with 122 patients that had given blood samples at baseline and at least at one follow-up (I = 51, C = 71). Patients 20 year or older with colorectal cancer were eligible. Exclusion criteria were emergency surgery, local surgery, language problems or inability to perform intervention. INTERVENTIONS: Patients were computer-randomised to either a daily home-based aerobic exercise intervention (I), or to usual care (C). The intervention lasted two weeks before surgery and four weeks after discharge from hospital and consisted of medium-intensity aerobic exercise and inspiratory muscle training. Circulating concentrations of IGF-1 and IGFBP-3 were determined by blinded personnel at baseline, time of surgery and 4-6 weeks postoperatively. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome of this subpopulation report was change in IGF-1/IGFBP-3 ratio, IGF-1 and IGFBP-3 concentrations from baseline to surgery, and 4-6 weeks postoperatively. RESULTS: The IGF-1/IGFBP-3 ratio increased from baseline to surgery by 11% in I and 8% in C with no difference between groups (I vs. C: 1.04, 95%CI: 0.97-1.11; p = 1.000). Postoperative change was 5% in I and 3% in C with no difference between groups (I vs. C:1.03, 95%CI: 0.96-1.10; p = 1.000). Results concerning IGF-1 and IGFBP-3 also showed statistically significant dynamics over time with no difference between groups. No adverse events were reported. CONCLUSIONS: The home-based exercise program in our trial did not have any effect on IGF-1, or IGFBP-3. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov with identifier NCT02299596. This work was funded externally.

Self-assessed preoperative level of habitual physical activity predicted postoperative complications after colorectal cancer surgery: A prospective observational cohort study.

INTRODUCTION: There is a growing interest in physical activity in relation to recovery after surgery. One important aspect of measuring recovery after surgical procedures is postoperative complications. The aim of this study was to determine if there is an association between the preoperative level of habitual physical activity and postoperative complications in patients undergoing elective surgery for colorectal cancer. MATERIALS AND METHODS: 115 patients scheduled for elective surgery due to colorectal cancer between February 2014 and September 2015 answered a questionnaire regarding physical activity and other baseline variables. Physical activity was assessed using the Saltin-Grimby physical activity level scale. Complications within 30 days after surgery were classified according to Clavien-Dindo, and the Comprehensive Complications Index (CCI) was calculated. Primary outcome was difference in CCI and key secondary outcome was risk for CCI ≥20. RESULTS: Physically inactive individuals had a CCI that was 12 points higher than individuals with light activity (p = 0.002) and 17 points higher than regularly active individuals (p = 0.0004). Inactive individuals had a relative risk for a CCI ≥20 that was 65% higher than for individuals reporting light activity (95% confidence interval (CI) for relative risk (RR) = 1.1-2.5) and 338% higher than for regularly active individuals (95% CI for RR = 2.1-9.4). CONCLUSION: Self-assessed level of habitual physical activity before colorectal cancer surgery was associated with fewer postoperative complications measured with CCI, in a dose-response relationship.