The Assessment of Fatigue and Quality of Life in Patients With Bone Tumor, Undergoing Chemotherapy Treatment and Possible Predictive Factors
Conditions: Fatigue Syndrome, Chronic, Bone Tumor, Quality of Life
Sponsor: Istituto Ortopedico Rizzoli

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Title: The assessment of fatigue and quality of life in patients with bone tumor, undergoing 
chemotherapy treatment and possible predictive factors. 
 
Code: Fatigue-ONCO 
 
Sources of financing: this study is a spontaneous non-profit study 
 
Conflict of interest: No conflict of interest on the part of the principal investigator, nor of 
the Collaborators 
 
Principal Investigator:  Dr.ssa Paola Coluccino, SSD Chemioterapia 
Firma del PI _____________________________________ 
 
Promotor: Istituto Ortopedico Rizzoli – SSD Chemioterapia 
 
Co investigator: 
Mattia Morri, Physiotherapist,  Physical and Rehabilitative medicine 
Rita Boschi, Nurse, Chemotherapy ward 
Eugenio Brruku, Nurse, Chemotherapy ward 
Erika Romagnoli, Nurse, Chemotherapy ward 
Riccardo Boccomino, Nurse, Chemotherapy ward 
 
Acronyms used in the text 
BFI: Brief Fatigue Inventory 
EORTC QLQ C-30 
TESS: Toronto Extremity Salvage Score  

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BMI: Body mass index 
NRS: Numering Rate Scale 
CRF: Case Report Form 
 
Introduction 
Fatigue syndrome is defined as an altered physical, emotional and / or cognitive 
feeling of tiredness that is not proportional to the activities performed by the 
subject and interferes with the activity of daily life (NCCN, 2018, Bower, 2014). It is a 
clinical condition, linked to the oncological pathology, extremely widespread and in 
patients undergoing chemotherapy and / or radiotherapy it is common in 80% of patients 
(NCCN, 2018; Bower, 2014; Arajuo, 2017). 
At the same time this symptomatology is identified as under-estimated and under-treated. 
Hubbard et al (2014), in accordance with the guidelines, suggest the need to introduce 
assessment of fatigue as a screening element for normal clinical practice. Interventions 
aimed at increasing physical activity, psychosocial and pharmacological support can 
benefit patients even if a standard treatment model has not been described to date 
(Bower, 2014). One of the difficulties highlighted in the literature is the correct identification 
of this syndrome. Scott et al (2011) stress the need for systematic studies in cancer 
populations with different types of cancer and at different stages of the disease using 
patient-oriented fatigue assessment tools. The Brief Fatigue Inventory (BFI) is one of the 
scales used precisely in the evaluation of this syndrome and has proved to be a reliable 
and easy to use tool, also validated in Italian (Mendoza et al 1999, Catania et al. 2013). 
Several authors have also shown that reduced physical activity and a worse quality of life 
are associated with fatigue (Witt et al 2002; Stark et al 2012, Warner et al 2008), 
particularly in young patients (Poort et al 2017) . 

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In the area of bone tumors, the available data on fatigue syndrome are extremely poor and 
only two studies have emerged from the literature search. The study by Granada-Cameron 
et al (2011) describes the experience of 11 new sarcoma patients undergoing 
chemotherapy treatment. Fatigue had been described as the prevalent symptom and was 
related to a worse quality of life. 
Serveas et al (2003) observing patients two years after the conclusion of treatment for 
bone cancer found that in 28% of cases fatigue is a severe problem for patients. 
 
Objective 
The aim of the present study is to evaluate and describe the evolution over time of the 
fatigue and the quality of life of patients with bone tumor during the chemotherapy 
treatment and in the first phase of follow-up and to identify possible prognostic factors. 
Such knowledge is a necessary precondition for identifying patients and the periods most 
at risk due to the onset of fatigue, so as to be able to hypothesize adequate containment 
strategies. 
Setting: Rizzoli Orthopedic Institute. Department of Chemotherapy 
Methods 
Design: observational study  
Population: all patients belonging to the Chemotherapy ward will be recruited 
consecutively for a new antiblastic treatment protocol. The process of informing and 
collecting the participants' consent will take place during the first admission in which 
intravenous administration of the chemotherapy will be started. Potential participants will 
be identified / selected for recruitment through inclusion and exclusion criteria described 
below. Enrolled patients who will not continue the chemotherapy protocol within our 
Institute but at another facility will exit the study. 
 

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Inclusion criteria: 
all patients diagnosed with bone tumors who start a new chemotherapy treatment protocol, 
both on admission and on an outpatient basis at the Chemotherapy ward for its antiblastic 
treatment over 12 years of age. The NCCN Guidelines Cancer-Related Fatigue identifies 
appropriate screening with rating scales with scores from 0 to 10 precisely for patients 
older than 12 years. 
Exclusion criteria: 
patients with little knowledge of the Italian language due to the impossibility of completing 
the assessment scales. 
Primary outcome:  
the patient's Fatigue will be measured during the treatment period with antiblastic drugs 
and part of the followup period. To this end the BFI scale validated in Italian will be used 
(Mendoza et al 1999; Catania et al, 2013) which includes 9 items with a score for each of 0 
to 10 and a consequent total score from 0 to 90. The measurement will take place in 4 
times: the day of enrollment, 6 months, 12 months and 24 months after enrollment. 
Secondary outcome: 
the quality of life of patients measured by the EORTC QLQ C-30 scale (Aaronson et al, 
1993) and the level of autonomy measured by the TESS scale (Davis et al, 1996) in 4 
steps: the enrollment day , at 6 months, at 12 months and at 24 months from enrollment. 
Variables taken into consideration: through the literature search and the comparison 
between professionals of different disciplines (nurses, physiotherapists, oncologists) 
involved, a panel of variables was established to collect: 
 Age 
 sex 
  BMI 
 Smoking 
 diabetes 

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 cardiopathies (hypertension, previous heart attack, ...) 
 Comorbidity (pulmonary, renal, anemia, arthritis, neuromuscular complications, 
sleep disorders, pain, emotional distress) 
 Diagnosis, 
  presence of metastases at the entrance 
 type of chemotherapeutic protocol / drug that will be administered from the time of 
enrollment (Methotrexate, Cisplatin, Adriamycin, Ifosfamide, Elastomer Ifosfamide, 
Gemcitabine, 
Taxotere, 
Vincristine-Adriamycin-ifosfamide, 
Vincristine 
-
phosphamide-Dactomycin, 
Ifosfamide-etoposide, 
Temiri, 
Topotecan, 
Cyclophosphamide, Eribulin) 
 previous chemotherapy treatments: chemotherapy protocol / drugs already 
performed (Methotrexate, Cisplatin, Adriamycin, Ifosfamide, Elastomer Ifosfamide, 
Gemcitabine, 
Taxotere, 
Vincristine-Adriamycin-ifosfamide, 
Vincristine 
-
phosphamide-Dactomycin, 
Ifosfamide-etoposide, 
Temiri, 
Topotecan, 
Cyclophosphamide , Eribulina) and number of cycles already carried out. 
  number of therapy cycles carried out from the moment of enrollment (to be 
collected at the 24th month) 
 tumor location 
 surgery (date and type) 
  Perceived pain measured with the NRS scale in the 4 expected data collection 
times 
Data collection: the data will be collected at the Chemotherapy ward at the time of 
admission of the patient in the ward or of his access to the outpatient service. Nurses and 
the research physiotherapist will be responsible for collecting data by administering the 
assessment scales and consulting the patient's clinical documentation. Data collection 
times and specific collection methods are shown in the following tables: 

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1° day 
 
 
 
DIAGNOSIS/new protocol 
 
Consent/CRF 
 
6 months  
 
 
 
BFI 
 
BFI 
 
12 months 
 
 
QLQ  
 
QLQ 
 
BFI 
 
24 months 
  
TESS 
 
TESS 
 
QLQ 
 
BFI 
 
 
 
TESS      
 
QLQ 
 
 
 
TESS 
 
 
Variables 
 
Collection methods  
Responsible for 
the collection 
Age 
Health documentation - to be included in the 
enrollment form, then a calculation sheet 
Nurse 
Sex 
Health documentation - to be included in the 
enrollment form, then a calculation sheet 
Nurse 
BMI 
To be calculated: report the patient's weight and 
height at the entrance 
Nurse 
Smoking 
 
OBSERVATION sheet (CRF): report in a 
calculation sheet 
Nurse 
diabetes 
 
OBSERVATION sheet (CRF): report in a 
calculation sheet 
Nurse 
cardiopathies 
OBSERVATION sheet (CRF): report in a 
calculation sheet 
Nurse 
Diagnosis 
Enrollment form: to be reported in the 
calculation sheet 
Nurse 
presence of 
Sanitary documentation: to be included in the 
Nurse 

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metastases at the 
entrance 
OBSERVATION (CRF) form, then calculation 
sheet 
type of 
chemotherapeutic 
protocol 
Enrollment form: to be reported in the 
calculation sheet 
Nurse 
previous 
chemotherapy 
treatments 
Health documentation - to be included in the 
enrollment form, then a calculation sheet 
Nurse 
number of 
therapy cycles 
OBSERVATION sheet (CRF): to be found in 
health documentation and then in the 
calculation sheet) 
Nurse 
tumor location 
 
Enrollment form: to be reported in the 
calculation sheet 
Nurse 
surgery (date and 
type) 
OBSERVATION sheet (CRF): report in a 
calculation sheet 
Nurse 
Pain 
Measured with NRS scale. Data present in the 
BFI Sheet: to be reported in the calculation 
sheet  
Nurse 
Autonomy level 
TESS scale: self-filled by the patient (6-12-24 
months from enrollment) 
Physiotherapist 
 
Statistical analysis: The characteristics of the sample will be described using the mean 
and standard or median deviation and interquartile range for quantitative variables and 
absolute and percentage frequencies for qualitative variables. Simple and multiple linear 
regression analyzes will be performed and to identify predictors of primary and secondary 
outcome. 
Sample size: In a pilot study of 19 patients at the Chemotherapy SSD the average BFI 
score was 31.6 with DS 19.1 at a mean follow-up of 5.2 months and DS 3.7. On the basis 
of this data, the number of variables taken into consideration equal to 15 in a multiple 
linear regression, an effect size of 0.1, an alpha value of 0.05 and a power of 80% the 

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number of patients to be enrolled is equal to 183. The sample size was calculated with 
Stata 15.0. 
Duration of the study: The project lasted 5 years as follows: 
Month 1-3 Meeting and training of the team involved in the study 
Months 3–36 Patient enrollment and data collection. 
Months 36-48 Construction of the database and preliminary analysis 
Months 48-60 Follow-up and Statistical analysis of data 
The approval date of the Ethics Committee will be considered as the starting date of the 
trial. 
Safety assessment: as this is an observational study, patients will be treated in 
accordance with the rules of good clinical practice and in accordance with the protocols 
regularly used in the operating unit involved. 
Data management and informed consent: the personnel designated by the Investigator 
must report the information required by the protocol in the CRF form and subsequently in 
the prepared database. Each potential participant will be fully explained the progress of the 
study and will be given the opportunity to ask questions and receive answers to all his 
doubts. The informed consent form must be signed by the participant or a legally 
authorized representative prior to his participation. Patient documentation must be able to 
demonstrate that consent was given prior to participation in the study. A copy of the 
informed consent form must be left to the patient. The consent form, signed by the patient, 
must be kept at the site. 
Approval by the Ethics Committee: This protocol, the informed consent form and all the 
necessary relevant information related to the study must be submitted to the Ethics 
Committee for evaluation and must be approved before the start of the study. The study 
will be conducted in accordance with international standards ISO 14: 155, with the Good 
Clinical Practice and with the national laws in force. 

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Confidentiality of data and ownership of results: Adequate documentation will be 
maintained for everything concerning the patient's clinical data, work sheets, nursing 
notes; the database will be available in a protected environment and access allowed only 
with Password. The confidentiality of the patient's sensitive data is guaranteed by the 
Investigator. 
Publication of Results: The main investigator undertakes to produce the final report, 
publish all the data collected as described in the protocol and ensure that the data is 
reported responsibly and consistently. In particular, the publication of the data deriving 
from this study will take place regardless of the results obtained. The transmission or 
diffusion of the data, through scientific publications and / or presentation at congresses, 
conferences and seminars, will take place exclusively following the merely statistical 
elaboration of the same, or in any case in an absolutely anonymous form. 
 
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