The intervention group will follow a physical exercise and lifestyle counselling program.

the intervention group will follow a physical exercise and health counselling intervention--see below.

The exercise program will be performed in the hospital gymnasium (3 supervised sessions/week of aerobic and muscle strength exercises) or in the patients' room (during phases of treatment-induced immunodepression, where isolation is needed to prevent infections). It will also include specific training of the respiratory ('inspiratory') muscles (e.g., diaphragm) on 5 days/week. The counselling program will include psychological (once weekly), nutritional (twice monthly), support (with survivors of adolescent cancer, twice/month) and educational (for relatives/caregivers, once monthly) sessions.

lifestyle and physical exercise

Alejandro Lucia

The investigators will study the effects of an inhospital exercise intervention combined with lifestyle--including diet--counselling along the duration of treatment (neoadjuvant \[solid tumours\]/intense chemotherapy \[leukemias\], expected median duration 5-6 months) on several health-related variables. Participants will be recruited from 3 hospitals in Madrid (Spain). Inclusion criteria: male/female aged 12-19 years, newly diagnosed with a malignant extracranial tumour; not having received any type of therapy--except surgery--at the time of diagnosis; adequate health status (Karnofsky/Eastern Cooperative Oncology Group scale score ≥50/2); to understand Spanish language and to provide written informed consent. The investigators will recruit ≥136 participants and conduct a randomised controlled trial. In addition to usual care, the control group will be informed of the benefits of a healthy lifestyle. The intervention group will follow a physical exercise and lifestyle counselling program. The exercise intervention will be performed in the hospital gymnasium, except for neutropenic phases--during which time sessions will be performed in the patients' ward--and will also include inspiratory muscle training). Health counselling will include a psychological intervention based on motivational interviewing techniques, guidance by a nutritionist, and support sessions with survivors who will share their experiences with the study participants. The following outcomes will be assessed at baseline (diagnosis), end of treatment, and at 3-month follow-up in all participants: echocardiography-determined left ventricular function (primary outcome); and blood pressure, blood lipids, body composition, physical activity levels, energy intake, cardiorespiratory fitness, muscle strength, functional mobility, health-related quality of life, cancer-related fatigue, stress coping, anxiety, depression, clinical variables, and potential biological underpinnings of exercise multisystemic benefits (metabolic and inflammatory \[cytokine panel\] markers, plasma proteome, gut microbiome, and immune function).

Background. Health promotion interventions are needed during adolescent cancer treatment to facilitate the acquisition of good health practices as patients transition to survivorship. Although meta-analytical evidence supports the health benefits of exercise in the context of childhood cancer, there is scant data focusing solely on adolescents.

Hypothesis and objectives. The investigators hypothesise that an inhospital exercise intervention combined with lifestyle counselling during treatment for adolescent cancer will provide several health benefits, particularly related to the cardiometabolic profile. Thus, the investigators will study the effects of an inhospital exercise intervention combined with lifestyle--including diet--counselling along the duration of treatment (neoadjuvant \[solid tumours\]/intense chemotherapy \[leukaemias\], expected median duration 5-6 months) on several health-related variables.

Setting and Methods. Participants will be recruited from 3 hospitals in Madrid (Spain). Inclusion criteria: male/female aged 12-19 years, newly diagnosed with a malignant extracranial tumour; not having received any type of therapy--except surgery--at the time of diagnosis; adequate health status (Karnofsky/Eastern Cooperative Oncology Group scale score ≥50/2); to understand Spanish language and to provide written informed consent. The investigators will recruit ≥136 participants and conduct a randomised controlled trial (1:1 ratio randomisation with a block on gender and tumour type \[leukaemias/lymphomas\]). In addition to usual care, the control group will be informed of the benefits of a healthy lifestyle. The intervention group will follow a physical exercise and lifestyle counselling program. The exercise intervention will be performed in the hospital gymnasium (3 sessions/week of aerobic and resistance exercises), except for neutropenic phases--during which time sessions will be performed in the patients' ward--and will also include inspiratory muscle training (5 days/week). Health counselling will include a psychological intervention (1 session/week) based on motivational interviewing techniques, guidance by a nutritionist (2 sessions/month), and support sessions (1/month) with survivors (≥5-year survivorship) who will share their experiences with the study participants. The following outcomes will be assessed at baseline (diagnosis), end of treatment, and at 3-month follow-up in all participants: echocardiographydetermined left ventricular function (primary outcome); and blood pressure, blood lipids, dual-energy X-ray absorptiometry-determined body composition (fat \[including visceral adipose tissue\]/lean mass, bone mineral content/density), accelerometry-determined physical activity, dietary recall determined energy intake, cardiorespiratory fitness, muscle strength, functional mobility, health-related quality of life, cancer-related fatigue, stress coping, anxiety, depression, clinical variables (survival, treatment tolerability, hospitalisation length, infections), and potential biological underpinnings of exercise multisystemic benefits (metabolic \[glucose homeostasis indicators, high-sensitivity C-reactive protein\] and inflammatory \[cytokine panel\] markers, plasma proteome, gut microbiome, and immune function \[lymphocyte subpopulations, natural killer cell cytotoxicity\]) (secondary outcomes).

The investigators will apply a two-arm RCT design, following the Consolidated Standards of Reporting Trials recommendations (1:1 randomisation ratio using a computer-generated random allocation sequence with a block on gender and main tumour type \[leukaemias/solid tumours\])

Assessment staff will be blinded to participant randomisation assignment. Yet, because of the nature of the study, it will not be possible to conceal the group assignment from the staff (i.e., fitness specialists, psycho-oncologists and nutritionists) involved in the different intervention (physical exercise and health counselling) sessions. Participants will be explicitly informed on the group to which they will be assigned as well as on the study hypotheses and will be reminded not to discuss their randomisation assignments with assessment staff and/or other patient.

Exercise and Lifestyle in Adolescent Cancer (HEALTHYADOL)

Exercise and Lifestyle Intervention for Patients With Adolescent Cancer: a Randomised Controlled Trial (HEALTHY ADOL)

Echocardiography-determined LV ejection fraction (unit = %)

Echocardiography-determined LV fractional shortening (unit = %)

Arterial blood pressure (BP) (ausculatory method) (units = mmHg)

Total/HDL/LDL-cholesterol will be quantified with an automated chemistry analyser (units = mg/dL).

Tiglycerides will be quantified with an automated chemistry analyser (units = mg/dL).

DXA-determined total lean and fat mass (grams)

DXA-determined bone mineral density (unit = g/m2)

PA levels (moderate/vigorous PA) determined using triaxial accelerometry (units =minutes/week)

PA levels (moderate/vigorous PA) determined using triaxial accelerometry (units = minutes/week)

3-day 24 h-dietary recalls to record the participants' energy intake by either themselves or parents/caregivers.

3-day, 24 h-dietary recalls will be used to record the participants' energy intake by either themselves or parents/caregivers. The investigators will provide participants with instructions on how to obtain a correct food record. Dietary recall data will be analysed using Dietsource 3.0 (Novartis) to determine total energy intake (kcal)

3-day 24 h-dietary recalls to record the participants' energy intake by either themselves or parents/caregivers.

3-day, 24 h-dietary recalls will be used to record the participants' energy intake by either themselves or parents/caregivers. The participants will provide participants with instructions on how to obtain a correct food record. Dietary recall data will be analysed using Dietsource 3.0 (Novartis) to determine protein, fat, carbohydrate, and fiber intake (g/day)

VO2peak will be determined with 'breath-by breath' analysis of expired gases on a metabolic cart using a ramp-like treadmill--or arm-crank ergometer--test (units = mL/kg/min)

The 5-repetition maximum (commonly abbreviated as 5RM), which is the maximum strength capacity to perform 5 repetitions until momentary muscular exhaustion, will be measured for leg press and bench press (units = kg).

PImax (units = cmH20) will be determined using a mouth pressure meter with the best result from 3 attempts (interspersed with rest periods of ≥1 min-duration) taken.

Health-related QoL (HRQoL) (Paediatric Quality of Life Inventory \[PedsQL\] 3.0 Cancer Module, designed to measure paediatric/adolescent cancer specific HRQoL) (0 to 100 scale, with higher scores indicating better HRQoL)

Health-related QoL (HRQoL) (Paediatric Quality of Life Inventory \[abbreviated as PedsQL\] 3.0 Cancer Module, designed to measure paediatric/adolescent cancer specific HRQoL) (0 to 100 scale, with higher scores indicating better HRQoL)

Cancer-related fatigue (Paediatric Quality of Life (PedsQL) Multidimensional Fatigue Scale) (0 to 100 score, higher scores meaning higher fatigue)

Cancer-related fatigue (Paediatric Quality of Life (PedsQL) Multidimensional Fatigue Scale) (0 to 100 score, higher scores meaning higher fatigue

Stress coping (General form of the Adolescent Coping Scale) (0 to 20 scale, with higher scores indicating higher resilience to stress)

Anxiety (six-item short-form of the state scale of the Spielberger State-Trait Anxiety Inventory \[abbbreviated as STAI\]) (0 to 100 score, with higher scores reflecting higher anxiety levels)

Anxiety (six-item short-form of the state scale of the Spielberger State-Trait Anxiety Inventory \[abbreviated as STAI\]) (0 to 100 score, with higher scores reflecting higher anxiety levels)

Depression (Child Depression Scale) (0 to 52 scale, with higher scores reflecting more depression)

Survival (numebr of days from diagnosis to the end of the study or death)

Survival (number of days from diagnosis to the end of the study or death)

Treatment tolerability (number of days of treatment interruption/delay

Total hospitalisation length (number of days)

Common Toxicity Criteria for Adverse Events \[CTCAE, global score, 1 (low toxicity) to 5 (highest\])

Homeostasis model assessment-insulin resistance index (HOMA-IR) (molar units)

Panel of 21 cytokines/chemokines measured in serum using Luminex® (all assessed in the same units, micrograms/dL)

The investigators will use liquid chromatography coupled to tandem-mass spectrometry (LC-MS/MS) to measure levels in blood of thousands of proteins

Spots Global Cancer Trial Database for lifestyle and physical exercise