Ensayo controlado aleatorio que prueba la viabilidad de una intervención de ejercicio y nutrición para pacientes con cáncer de ovario durante y después de la quimioterapia de primera línea (estudio BENITA)

Open access Original research
BMJ Open: first published as 10.1136/bmjopen-2021-054091 on 23 February 2022. Downloaded from http://bmjopen.bmj.com/ on September 4, 2023 at Universidad Peruana Cayetano
Randomised controlled trial testing the
feasibility of an exercise and nutrition
intervention for patients with ovarian
cancer during and after first-line
chemotherapy (BENITA-study)
Tabea Maurer,1 Matthias Hans Belau ‍ ‍,2 Julia von Grundherr,3 Zoe Schlemmer,4
Stefan Patra,5 Heiko Becher ‍ ‍,2 Karl-Heinz Schulz,5,6 Birgit-Christiane Zyriax,7
Barbara Schmalfeldt,4 Jenny Chang-Claude ‍ ‍1,8
To cite: Maurer T, Belau MH, ABSTRACT

von Grundherr J, et al. Strengths and limitations of this study
Objectives Advanced ovarian cancer is a severe
Heredia Facultad de Medicina. Protected by copyright.

Randomised controlled trial disease with major side effects caused by peritoneal
testing the feasibility of ► The trial uses objective measures to evaluate the
carcinomatosis, ascites and gastrointestinal involvement
an exercise and nutrition feasibility of an exercise and nutrition intervention in
intervention for patients with as well as exhaustive treatment like debulking surgery patients with ovarian cancer.
ovarian cancer during and and combination chemotherapy. Two most frequently ► The exercise and nutrition intervention commences
after first-line chemotherapy reported side effects are muscle wasting and malnutrition, during first-line chemotherapy and continues well
(BENITA-study). BMJ Open leading to frailty, decreased health-related quality of life into ovarian cancer survivorship.
2022;12:e054091. doi:10.1136/ (HRQoL) and cancer-related fatigue (CRF). As muscle ► The exercise and nutrition intervention has been
bmjopen-2021-054091 wasting and malnutrition often commence during first- developed by an interdisciplinary team of sport and
► Prepublication history for line chemotherapy and develop progressively into a nutrition experts.
this paper is available online. refractory state, an early intervention is warranted. This ► Sport and nutrition experts conducting the interven-
To view these files, please visit pilot study aimed to evaluate the safety and acceptance of tion and assessing the outcome in both groups could
the journal online (http://dx.doi. a combined exercise and nutrition intervention during and not be blinded due to the study design.
org/10.1136/bmjopen-2021- after first-line chemotherapy.
054091). Design The pilot study was conducted as a monocentric
1:1 randomised controlled trial (RCT) with an intervention randomised into IG (n=8) and CG (n=7). Eleven participants
TM and MHB are joint first
authors. group (IG) and a control group (CG). Participants were completed the study (completion rate, 73.3%), one patient
divided by chance into IG or CG. Information on group dropped out due to loss of interest, one due to poor health,
Received 09 June 2021 allocation was conveyed to the study coordinator one was lost to follow-up and one patient died.
Accepted 24 December 2021 responsible for making an appointment with the patients Conclusion The BENITA (Bewegungs- und
for the baseline assessment as well as the physiotherapist Ernährungsintervention bei Ovarialkrebs) study
and nutritionist responsible for the intervention and demonstrated the safety and acceptance of an exercise
outcome assessment in both groups. and nutrition intervention integrated into first-line therapy
Participants Eligibility criteria included women ≥18 and follow-up care of ovarian cancer. A large multicentre
years of age, diagnosed with ovarian cancer, tubal cancer RCT is planned to investigate the effectiveness of the
or peritoneal cancer and primary or interval debulking, intervention on HRQoL, CRF and survival and to establish
scheduled but not started adjuvant or neoadjuvant means of implementation into oncology guidelines and
chemotherapy and sufficient German-language skills. clinic routine.
Intervention The IG received a 12-month exercise and Trial registration number DRKS00013231.
nutrition programme, the CG continued to follow usual
© Author(s) (or their care. INTRODUCTION
employer(s)) 2022. Re-use Primary and secondary outcome measures Primary
Ovarian cancer is the second most common
permitted under CC BY-NC. No outcomes were recruitment rate, adherence to
commercial re-use. See rights gynecologic cancer in women and has the
intervention, completion rate and adverse events. In
and permissions. Published by addition, in-person assessments (eg, HRQoL, CRF, muscle fifth highest rate of cancer- related deaths
BMJ.
quality and function and dietary intake and quality) were for women in Germany1 with only 43% alive
For numbered affiliations see conducted at baseline (T0, before chemotherapy), week 9 5 years after diagnosis.2 Major side effects of
end of article. ovarian cancer and its treatment are cancer
(T1, mid-chemotherapy), week 19 (T2, after completion of
Correspondence to chemotherapy) and after 12 months of intervention (T3). cachexia, sarcopenia, frailty and malnutri-
Professor Jenny Chang-Claude; Results Of 60 eligible patients, 15 patients signed tion. All are leading to either loss of skeletal
j .chang-claude@uke.de informed consent (recruitment rate=25.0%) and were muscle mass and/or fat mass of the patient
Maurer T, et al. BMJ Open 2022;12:e054091. doi:10.1136/bmjopen-2021-054091 1

Open access
and are associated with decreased health-related quality not started adjuvant or neoadjuvant chemotherapy and
of life (HRQoL), cancer- related fatigue (CRF) and sufficient German-language skills. Exclusion criteria were
poorer outcome.3 4 As these syndromes share similar aeti- an Eastern Cooperative Oncology Group status of two or
ological factors such as reduced food intake, inflamma- worse, any physical or mental condition that would hinder
tion, hormonal changes, increased energy requirements execution or completion of the training programme
and reduced physical activity (PA),5 more than one can and study procedures, a private engagement in exercise
be present in the same patient at the same time. Hence, training above the WHO recommendation of 150 min of
a combined intervention consisting of an exercise and moderate-intensity activity per week17 or a diagnosis of an
nutrition programme may be most successful to address eating disorder.
these syndromes in patients with advanced cancer.6 7 Exer-
cise has been shown to significantly improve CRF, cardio- Patient and public involvement
respiratory fitness, HRQoL and even survival in breast The patient with organisation in Germany (Verein Eier-
and colon cancer.8 9 Adherence to lifestyle recommenda- stockkrebs Deutschland e.V.) represented by its first chair-
tions such as PA and nutrition before diagnosis was asso- person, Andrea Krull, has provided input to the project
ciated with a significantly higher HRQoL10 and decreased from a patient’s perspective, reviewed ethical issues and
risk of cancers.11 However, there is paucity of knowledge commented on consent forms.
on postdiagnosis PA or nutrition behaviour on prognosis
or HRQoL in patients with ovarian cancer. In observa- Procedure
tional studies, patients with ovarian cancer with greater Two gynaecologists identified and approached partici-
postdiagnosis PA were found to experience a significantly pants meeting inclusion criteria. After written informed
better HRQoL.12–14 Yet, randomised controlled trials consent, patients were randomised into the IG to receive

(RCTs) evaluating the benefits of an exercise and nutri- a 12-months exercise and nutrition programme or the
tion intervention on survival and HRQoL are rare. Two CG to receive usual care. Group allocation was performed
RCTs on bimodal exercise and nutrition programmes for by a statistician not involved in data collection. Informa-
patients with ovarian cancer are currently ongoing.15 16 tion on group allocation was conveyed to the study coor-
One commences intervention after completion of treat- dinator responsible for making an appointment with the
ment15 and one investigates the effect of an intervention patients for the baseline assessment as well as the phys-
during first-line chemotherapy.16 However, no current or iotherapist and nutritionist responsible for the interven-
previous RCT offers a care programme during and after tion, and outcome assessment in both groups.
first-
line chemotherapy, which is necessary to prevent In-
person assessments were conducted independent
deterioration due to treatment as well as support mainte- of study arm at baseline (T0), mid-chemotherapy (T1),
nance of lifestyle changes thereafter. after completion of chemotherapy (T2), and at 1-year
It was the aim of this study to determine the feasibility follow-up (T3). Assessments include HRQoL (European
of a combined exercise and nutrition intervention for Organisation for Research and Treatment of Cancer
patients with ovarian cancer during and after first-line (EORTC)-QLQ-C30,16 CRF (Multidimensional Fatigue
chemotherapy. Main endpoints of the pilot trial were Inventory (MFI-20)),18 nutritional risk (Nutritional Risk
recruitment rate, adherence, completion rate as well Score−2002),19 PA (Short Questionnaire to Assess Health
as adverse events (safety). Furthermore, assessments enhancing physical activity),20 performance diagnostics
requiring visits to the hospital (in-person assessments) as including 6 min walk test,21 hand grip strength (hand
planned for a main trial were conducted (eg, HRQoL, grip dynamometer, ‘Kern MAP 80k1’),22 accelerometer
CRF, muscular strength and quality, nutrition habits and (‘Actigraph wGT3X-BT’) and body composition (bioelec-
quality) to investigate acceptance and safety in patients tric impedance analysis (BIA), ‘AKERN BIA 101 Anni-
with ovarian cancer. versary’).23 A detailed overview on scheduled in-person
assessments is described elsewhere.24 Safety of the
programme was analysed through adverse events linked
METHODS to the intervention during all phases of the study. All anal-
Study design, setting and participants yses were performed using STATA MP, version V.17.
This pilot study was a monocentric 1:1 RCT with an
intervention (IG) and a control group (CG). The ethics Intervention
committee of the Faculty of Medicine at Hamburg Univer- Participants received personalised exercise and nutri-
sity approved the study protocol. The trial was regis- tion programmes and counselling that were tailored to
tered at the German Study Registry for Clinical Studies different phases of patient’s treatment and recovery as well
(DRKS00013231). Participants were recruited from the as individual needs throughout the trial. In both phases
Department of Gynecology at the University Medical of the exercise intervention, patients are given instruc-
Center Hamburg-Eppendorf (UKE) in Germany at diag- tions and encouraged to participate in a daily 15–30 min
nosis. Eligibility criteria included women ≥18 years of age, unsupervised home-based training that includes endur-
diagnosed with ovarian cancer, tubal cancer or peritoneal ance, resistance and balance exercises to be performed in
cancer and primary or interval debulking, scheduled but gradual increments. An exercise catalogue was developed
2 Maurer T, et al. BMJ Open 2022;12:e054091. doi:10.1136/bmjopen-2021-054091

Open access
by sports scientists and all exercises were categorised based patients met inclusion criteria and were invited into the
on their intensity. Each patient received an individually study. 45 refused to participate in the study. Main reasons
adapted programme consisting of exercises that are part were personal reasons, residence outside of Hamburg, not
of the catalogue. The programme was adjusted each week willing to be randomised and no interest in the research.
(phase I) or every other week (phase II) if needed based Fifteen patients signed informed consent (recruitment
on the patients’ individual abilities and current needs. rate, 25.0%) and were randomised into IG (n=8) and CG
Exercises using abdominal muscles were not included (n=7). Eleven participants completed the study (comple-
till full recovery from surgery. The exercise catalogue tion rate, 73.3%), one patient dropped out due to loss
used to build the exercise programmes can be found in of interest, one patient due to poor health (recurrence),
the supplements. The nutrition intervention in phase I one patient was lost to follow-up (could not be reached via
aimed to reduce malnutrition risk by increasing protein phone or mail) and one patient died. Figure 1 provides
and calorie intake. During chemotherapy, patients were the flow of participants through the study.
supervised by a nutritionist every 3 weeks. Those who were Table 1 summarises the baseline characteristics of
in need of an increased calorie and protein intake were participants by group assignment. The mean age of
advised to consume several smaller meals throughout the participants was 56.5±14.4 years ranging from 21 to
the day and, if necessary, to increase the use of oils and 77 years, with an average of 33.9±17.0 days since initial
butter. Furthermore, patients were educated about suit- diagnosis. The majority (73.3%) of patients was diag-
able types of foods and drinks that are high in protein, nosed as having advanced stage disease (stage III or IV).
fat or energy. If deemed necessary, oral sip feeding was After surgery, eight patients had no residual tumour, five
suggested. These recommendations were based on the patients’ tumours were resected to smaller than 1 cm and
patients’ development in weight as well as other body two patients’ tumours had residual tumour larger than 1

composition parameters derived from BIA measurements cm.
(eg, phase angle, muscle mass). In phase II (weeks 19–52) All 15 participants enrolled in the study completed
after chemotherapy, monthly nutrition counselling was T0 and T1 assessments. Between T1 and T2, one patient
focused on the Mediterranean diet, shown to reduce in the IG died and another dropped out due to loss of
malnutrition and cancer risk. To monitor adherence and interest. The remaining 13 patients completed the T1
progress in phase I, participants received a weekly tele- assessment. Between T2 and T3, a patient of the IG was
phone call by a sports scientist, and triweekly by a nutri- lost to follow-up and a patient of the CG dropped out due
tionist. In phase II, patients received monthly counselling to a recurrence. All 11 patients still enrolled in the study
by telephone or in person. The intervention is described completed the final assessment. Table 2 provides detailed
in more detail elsewhere.24 information on adherence to different assessments and
time points by group assignment. Adherence to the exer-
Statistical methods cise intervention in terms of completed intervention
Recruitment rate was defined as the ratio of patients sessions (face-to-face, by telephone) was 83.7% for exer-
eligible to participate and patients who signed informed cise intervention (phase I, 83.2%; phase II, 85.1%) and
consent. Completion rate was defined as the ratio of 76.8% for nutrition intervention (phase I, 92.3%; phase
patients who signed informed consent and those who II, 59.6%).
completed the 12- month intervention. General adher- Adherence to the exercise and nutrition programme
ence to the intervention was defined as the ratio of is shown in table 3. During phase I, five out of eight
planned and completed counselling sessions. Adherence patients documented their weekly home-based exercise
to the exercise programme was further assessed using for a total of 14–18 weeks. One patient documented
exercise diaries filled out every week until week 18 and their daily home-based exercise for 10 weeks, another
once a months until 12 months follow-up. Adherence patient dropped out after 6 weeks and one patient died
to the nutrition intervention in phase I was described in during phase I without documentation of home-based
terms of changes in protein and caloric intake compared training. Patients trained between 90 min/week and 180
with baseline. During phase II, adherence to the nutri- min/week. In phase II, three patients documented their
tion intervention was interpreted in terms of changes in exercise for 30–34 weeks. Two patients stopped their
MEDAS (Mediterranean Diet Adherence Screener) score documentation after 12 and 4 weeks, respectively. Two
points between T0 and T3.25 Descriptive analyses were patients dropped out of the study and one patient did not
conducted for all parameters assessed during the study. continue to document their daily practice, but remained
No inferential statistics were used as this feasibility trial in the study. In phase II, most patients trained for up to
was not powered for this purpose. 90 min/week.
Adherence to the nutrition intervention in terms of
caloric and protein intake showed that patients of the IG
RESULTS increased their protein intake from 65.8 g/day at baseline
Characteristics and feasibility (T0) to 107.9 g/day at T2. The calorie intake increased
Of 67 patients with initial diagnosis of ovarian cancer from 1860 kcal/day at T0 to 2389 kcal/day at T2. In phase
from April 2018 to Sept 2019 screened for eligibility, 60 II, adherence to the nutrition intervention based on the

Open access
Figure 1 Flow diagram of participant recruitment and randomisation.
MEDAS score showed that patients of the IG increased min walk distance from 411 m at baseline to 475 m at
their MEDAS scores from a median of 7.0 at baseline to a T3, whereas members of the CGs decreased their distance
median of 10 score points at week 52 (T3). from 440 m to 380 m. Patients of the IG increased their
Safety of the intervention was defined through any hand grip strength from 22.0 kg to 24.8 kg (median), the
adverse events that could be linked to either the exer- CG showed a slightly lower increase (from 21.8 kg to 22.4
cise or the nutrition intervention. There were no adverse kg). In terms of nutrition, calorie intake during chemo-
events reported to be due to the intervention or in-person therapy increased in both IG and CG. The IG showed a
assessments.
larger increase in protein intake from baseline to T1 and
Descriptive statistics of in-person assessments T2 compared with controls. Adherence to Mediterranean
Table 4 and figures 2 and 3 display descriptive results of diet or nutritional risk was comparable in IG and CG.
in-person assessments at different time points by group The HRQoL increased from baseline to T3 from 37.5
assignment. Participants who received personalised exer- to 70.8 score points in the IG and from 41.7 to 50.0
cise and nutrition programmes increased their median 6 score points in the CG. Both total and physical fatigue

Open access
Table 1 Baseline characteristics of participants by group assignment
All participants Intervention group Control group
N (=15) % N (=8) % N (=7) %
Age Median (range) 58 (21–77) 52 (21–64) 65 (48–77)
Education* Low 1 6.7 0 0.0 1 14.3
Medium 8 53.3 5 62.5 3 42.9
High 6 40.0 3 37.5 3 42.9
Smoking status Never smoker 8 53.3 4 50.0 4 57.1
Former smoker 5 33.3 3 37.5 2 28.6
Current smoker 2 13.3 1 12.5 1 14.3
Alcohol use per week <1 g 5 33.3 3 37.5 2 28.6
1–12 g 1 6.7 0 0.0 1 14.3
13–24 g 3 20.0 3 37.5 0 0.0
25–48 g 4 26.7 1 12.5 3 42.9
49–60 g 2 13.3 1 12.5 1 14.3
Body mass index Underweight (<18.5) 1 6.7 1 12.5 0 0.0
Normal weight (18.5–24.9) 9 60.0 4 50.0 5 71.4

Overweight (25.0–29.9) 2 13.3 1 12.5 1 14.3
Obesity (≥30.0) 3 20.0 2 25.0 1 14.3
Sports† 0–4 MET h/week 9 60.0 6 75.0 3 42.9
5–10 MET h/week 1 6.7 1 12.5 0 0.0
>10 MET h/week 5 33.3 1 12.5 4 57.1
Cancer stage‡ I 2 13.3 1 12.5 1 14.3
II 2 13.3 0 0.0 2 28.6
III 9 60.0 6 75.0 3 42.9
IV 2 13.3 1 12.5 1 14.3
Tumour size postop Tumor-free 8 53.3 4 50.0 4 57.1
<1 cm 5 33.3 2 25.0 3 42.9
>1 cm 2 13.3 2 25.0 0 0.0
Treatment Adjuvant chemotherapy 12 80.0 6 75.0 6 85.7
Neo-adjuvant chemotherapy 3 20.0 2 25.0 1 14.3
*CASMIN classification35
†SQUASH questionnaire20
‡FIGO classification36
CASMIN, Comparative Analysis of Social Mobility in Industrial Nations; FIGO, International Federation of Gynecology and Obstetrics; MET,
metabolic equivalent of task; SQUASH, Short Questionnaire to Assess Health enhancing physical activity.
decreased from T0 to T3 and was somewhat stronger in Patients with ovarian cancer are not only seriously ill
IG than CG for physical fatigue. but also undergo exhausting abdominal surgery and
chemotherapy. Therefore, it is not surprising that the
majority of patients with ovarian cancer report an inactive
DISCUSSION lifestyle and do not meet recommendations after diag-
This pilot trial investigating the safety, acceptance and nosis and treatment.26 Common side effects of ovarian
feasibility of a combined exercise and nutrition inter- cancer and its treatment are muscle wasting and malnour-
vention during and after first- line chemotherapy in ishment. Both can be targeted by nutrition and exercise
patients with ovarian cancer demonstrated that patients programmes.6 Consequently, it can be assumed that
were motivated to enrol and adhere to the programme patients with ovarian cancer may benefit from an individ-
and that the exercise and nutrition intervention as early ualised exercise and/or nutrition intervention to an even
as during chemotherapy were save for this vulnerable greater extent than already demonstrated in patients with
patient group. breast and colon cancer.8 9

Open access
Table 2 Adherence to assessment time points
N* % N* % N* %
Exercise assessment Performance diagnostics T0† 14/15 93.3 7/8 87.5 7/7 100.0
T1 11/15 73.3 6/8 75.0 5/7 71.4
T2 12/13 92.3 6/6 100.0 6/7 85.7
T3 11/11 100.0 5/5 100.0 6/6 100.0
T0 – T3 48/54 88.9 24/27 88.9 24/27 88.9

Accelerometer‡ T0 13/15 86.7 6/8 75.0 7/7 100.0
T1 11/15 73.3 6/8 75.0 5/7 71.4
T2 10/13 76.9 5/6 83.3 5/7 71.4
T3 11/11 100.0 5/5 100.0 6/6 100.0
T0 – T3 45/54 83.3 22/27 81.5 23/27 85.2
Nutrition diagnostics T0 14/15 93.3 8/8 100.0 6/7 85.7
T1 15/15 100.0 8/8 100.0 7/7 100.0
T2 12/13 92.3 6/6 100.0 6/7 85.7

T3 11/11 100.0 5/5 100.0 6/6 100.0
T0 – T3 52/54 96.3 27/27 100.0 25/27 92.6
Case report form§ T0 15/15 100.0 8/8 100.0 7/7 100.0
T1 15/15 100.0 8/8 100.0 7/7 100.0
T2 12/13 92.3 6/6 100.0 6/7 85.7
T3 11/11 100.0 5/5 100.0 6/6 100.0
T0 – T3 53/54 98.2 27/27 100.0 26/27 96.3
*Number of participants assessed/number eligible.
†T0 = baseline, T1=mid-chemotherapy, T2=after completion of chemotherapy, T3=1-year follow-up.
‡Worn at home for a week at each time of assessment.
§Included all questionnaires applied In the study.
As ovarian cancer is often diagnosed at a late stage (phase I, 92.3%; phase II, 59.6%). There were no adverse
of disease and the median age at initial diagnosis is 62 events associated with the intervention documented
years, it was anticipated that the recruitment and comple- throughout the trial. Therefore, this study, to our knowl-
tion rate would be lower than that reported in studies edge, is the first to show that a combined nutrition and
including patients with cancer diagnosed at an early stage exercise intervention in patients with ovarian cancer
or at a younger age.27 In our randomised feasibility trial, during and after first-line chemotherapy is feasible, safe
recruitment rate was 25.0%, which is in line with recruit- and accepted.
ment rates of 16%–63% and a retention rates of 70–100 To date, few RCTs on exercise and/or nutrition in
stated in a recent review.14 Reported reasons for refusal ovarian cancer exist and those few available mainly
of participation were symptoms, illness and exhaustion.14 recruited patiens after completion of treatment. Thus,
These reasons hold true for our study as well. In addi- these studies in principle predominantly recruited
tion, many patients declined to take part due to a distant patients in remission free of progression. The Women’s
residence, which was also the reason for not undergoing Activity and Lifestyle Study in Connecticut (WALC)28
chemotherapy at UKE, thus requiring separate trips to trial, a 6-month exercise intervention in ovarian cancer,
UKE for the study. Others did not participate because for example, included patients up to 4 years following
they were not willing to risk randomisation into the CG. initial diagnosis, and the patients’ sample was, therefore,
Patients who consented to participate in the study showed heterogeneous. The Resistance and Endurance exercise
a high commitment, and only two patient(s) dropped out, After ChemoTherapy (REACT) study9 including a few
leading to a completion rate of 73.3%. Adherence to the patients with ovarian cancer among other cancer survivors
exercise intervention in terms of completed counselling used a 12-week exercise intervention without combined
sessions was higher than reported by a systematic review14 nutrition counselling shortly after completion of treat-
with 83.7% for exercise intervention (phase I, 83.2%; ment. The currently ongoing Lifestyle Intervention for
phase II, 85.1%) and 76.8% for nutrition intervention Ovarian Cancer Enhanced Survival (LIVES) study15 also

Open access
Table 3 Adherence to the implementation of exercise and nutrition programme among participants from the intervention
group
Exercise programme
Number of Days per week Minutes per week Rating of perceived exertion (RPE)
Participant weeks reported Median Borg’s RPE scale37
Phase I P1 15 5.2 Up to 90 min Very light to light9–11
(week 1–18) P2 18 5.7 Up to 90 min Light to somewhat hard11–13
P3 6 4.3 Up to 90 min Light to somewhat hard11–13
P4 14 5.4 90 to 180 min Light to somewhat hard11–13
P5 10 5.4 Up to 90 min Somewhat hard to hard13–15
P7 18 5.1 Up to 90 min Very light to light9–11
P8* 0 0.0 – –
Phase II P1† 0 0.0 – –
(week 19–52) P2 32 4.1 Up to 90 min Light to somewhat hard11–13
P3‡ 0 0.0 – –

P5 12 2.0 Up to 90 min Light to somewhat hard11–13
P6 34 2.0 Up to 90 min Somewhat hard13
P7 34 6.1 Up to 90 min Somewhat hard13
P8* 0 0.0 – –
Nutrition programme
Protein intake Mediterranean diet§
(Gram per day) (Sum score)
Mean (SD) Median Mean (SD) Median
Phase I Week 1 65.8 (16.4) 64.8 7.0 (2.3) 7.0
(week 1–18)
Week 9 96.7 (29.4) 90.3 7.8 (2.1) 8.0
Phase II Week 19 107.9 (18.1) 113.5 8.7 (1.0) 9.0
(week 19–52)
Week 52 90.9 (9.1) 93.1 9.2 (1.6) 10.0
*Died in hospital.
†Dropped out.
‡Lost to follow-up.
§MEDAS sum score.
MEDAS, Mediterranean Diet Adherence Screener.
investigates the effect of a 24-month lifestyle intervention and/or nutrition interventions during first- line chemo-
after treatment for patients with ovarian cancer. Only therapy reported increased moderate to strenuous PA to be
the ongoing Physical Activity and Dietary intervention in correlated with improvements in HRQOL30–32 and physical
women with OVArian cancer (PADOVA) study offers a functioning (eg, muscular strength, 6 min walking test)30–32
combined exercise and nutrition intervention during first- as well as reduced fatigue.31 32 Our study showed similar
line chemotherapy.29 However, the exercise and nutrition tendencies for the 6 min walking test, physical fatigue as well
intervention are limited to the duration of chemotherapy as global health. However, these results are descriptive only
only, whereas our study aims to start with chemotherapy and no RCT exists to prove effectiveness of a combined exer-
and to continue well into ovarian cancer survivorship cise and nutrition intervention during and/or after primary
to ensure maintenance of the recommended lifestyle. care in patients with ovarian cancer.
Previous studies on postdiagnosis exercise in ovarian

cancer have shown that exercise leads to improvements CONCLUSION
in HRQOL, fatigue and additional physical and psycho- To date, guidelines on care programmes for patients
logical outcomes.14 The few feasibility studies on exercise with ovarian cancer in Germany are based solely on

Open access
Table 4 Results of assessments at different time points by group assignment
Mean (SD) Median Mean (SD) Median Mean (SD) Median
6 min walking test T0* 397.5 (109.8) 411.0 369.7 (126.3) 325.7 436.4 (77.3) 440.0
meter
T1 489.0 (95.5) 490.0 483.9 (96.2) 495.0 495.1 (105.6) 458.8
T2 496.2 (116.5) 507.7 511.9 (80.9) 524.4 477.4 (157.8) 410.0
T3 492.8 (134.6) 475.0 542.4 (91.1) 570.7 451.5 (158.4) 380.0
Hand grip strength† T0 22.4 (7.0) 21.9 22.2 (8.7) 22.0 22.6 (4.7) 21.8
kilogram
T1 24.1 (7.5) 21.6 23.5 (6.4) 21.6 25.0 (9.9) 21.3
T2 25.2 (6.9) 24.6 23.0 (6.0) 23.2 27.8 (7.6) 25.8
T3 25.6 (6.7) 24.8 26.3 (5.9) 24.8 25.1 (7.8) 22.4
Mediterranean diet‡ T0 7.0 (1.9) 8.0 7.0 (2.3) 7.0 7.0 (1.4) 8.0
sum core
T1 8.4 (2.2) 9.0 7.8 (2.1) 8.0 9.1 (2.2) 9.0
T2 9.0 (1.8) 9.0 8.7 (1.0) 9.0 9.3 (2.3) 9.5
T3 9.2 (1.9) 10.0 9.2 (1.6) 10.0 9.2 (2.3) 9.0
Nutritional risk§ T0 3.4 (1.1) 3.0 3.5 (1.2) 3.5 3.3 (1.1) 3.0
sum score
T1 3.1 (1.3) 3.0 3.0 (1.5) 2.5 3.3 (1.1) 3.0
T2 2.4 (1.8) 2.5 2.5 (2.1) 3.0 2.3 (1.6) 2.0

T3 0.4 (0.7) 0.0 0.2 (0.5) 0.0 0.5 (0.8) 0.0
Protein intake T0 68.0 (13.3) 64.8 65.8 (16.4) 64.8 70.6 (9.1) 68.1
gram per day
T1 89.6 (30.4) 87.0 96.7 (29.4) 90.3 78.2 (31.4) 79.6
T2 104.0 (23.5) 113.3 107.9 (18.1) 113.5 100.1 (29.1) 97.3
T3 89.3 (23.0) 93.1 90.9 (9.1) 93.1 87.9 (31.4) 93.6
Caloric intake T0 1830 (382) 1816 1860 (388) 1987 1795 (409) 1663
kilocalories per day
T1 2237 (612) 2439 2380 (429) 2350 2010 (835) 2439
T2 2237 (513) 2439 2389 (372) 2474 2147 (635) 2071
T3 2206 (548) 2355 2105 (398) 2219 2291 (675) 2387
HRQoL¶
Global health status T0 40.0 (10.5) 41.7 40.6 (8.3) 37.5 39.3 (13.4) 41.7
sum score
T1 55.6 (27.8) 66.7 62.5 (20.4) 66.7 47.6 (34.3) 33.3
T2 59.7 (20.7) 54.2 58.3 (14.9) 54.2 61.1 (26.7) 54.2
T3 65.8 (19.8) 66.7 72.9 (8.0) 70.8 61.1 (24.5) 50.0
Physical functioning T0 59.1 (25.1) 66.7 54.2 (27.5) 53.3 64.8 (22.7) 66.7
sum score
T1 69.3 (23.1) 73.3 66.7 (23.9) 76.7 72.4 (23.5) 73.3
T2 70.6 (21.9) 76.7 76.7 (12.5) 80.0 64.4 (28.5) 63.3
T3 78.2 (16.9) 73.3 76.0 (17.4) 73.3 80.0 (17.9) 76.7
CRF**
General fatigue T0 17.6 (5.3) 18.0 18.6 (5.2) 17.5 16.6 (5.7) 18.0
sum score
T1 14.9 (6.3) 14.0 13.9 (5.1) 14.0 16.1 (7.7) 14.0
T2 14.5 (6.2) 15.0 15.2 (6.1) 15.0 13.8 (7.0) 13.0
T3 12.8 (6.2) 12.0 13.8 (7.2) 11.0 11.8 (5.6) 13.0
Physical fatigue T0 18.5 (6.0) 17.0 19.1 (6.7) 18.5 17.7 (5.5) 17.0
sum score
T1 14.0 (7.1) 15.0 12.3 (7.4) 9.5 16.0 (6.6) 17.0
T2 12.9 (5.8) 12.0 12.0 (4.9) 11.0 14.0 (7.3) 16.0
T3 11.6 (5.9) 9.5 11.0 (6.4) 7.0 12.2 (5.9) 12.0
*T0 = baseline, T1=mid-chemotherapy, T2=after completion of chemotherapy, T3=1-year FU.

†dominant hand.
‡MEDAS.
§NRS-2002.
¶EORTC QLQ-C30.
**MFI-20.
CRF, cancer-related fatigue; EORTC, European Organisation for Research and Treatment of Cancer; HRQoL, health-related quality of life; MEDAS, Mediterranean Diet Adherence
Screener; MFI, Multidimensional Fatigue Inventory; NRS, Nutritional Risk Score.

Open access
Figure 2 Descriptive results of in-person assessments at baseline (T0), mid-chemotherapy (T1), after completion of

chemotherapy (T2), and 1 year follow-up (T3) by group assignment. MEDAS, Mediterranean Diet Adherence Screener.
expert consensus.33 Although aftercare programmes patients who survive for more than 8 years up to 70%
for ovarian cancer survivors to improve HRQoL and will suffer long-
term sequelae of cancer treatment,
CRF are recommended, current treatment guidelines including reduced HRQoL and CRF.34 A home-based
include a further 15–24- month maintenance therapy personalised standardised care intervention programme
after completion of chemotherapy, which renders it beginning already during chemotherapy and continued
difficult for patients to receive inpatient rehabilitation post-
treatment will enable the majority of patients
after first-line therapy.33 Therefore, of about a third of to participate and further empower them to achieve

Open access
Figure 3 Descriptive results (continued) of in-person assessments at baseline (T0), mid-chemotherapy (T1), after completion of
chemotherapy (T2), and 1 year follow-up (T3) by group assignment. EORTC, European Organisation for Research and Treatment
of Cancer; MFI, Multidimensional Fatigue Inventory; NRS, Nutritional Risk Score.
6
long-
term adherence to recommended exercise and Department of Medical Psychology, University Medical Center Hamburg-Eppendorf,
nutrition behaviour. Hamburg, Germany
7
Thus, following this pilot study, it will be important to Midwifery Science—Health Care Research and Prevention, Institute for Health
conduct a multicentre RCT (1) to provide evidence of Services Research in Dermatology and Nursing (IVDP), University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
the effectiveness of a personalised combined exercise and 8
Division of Cancer Epidemiology, DKFZ, Heidelberg, Baden-Württemberg, Germany
nutrition intervention during adjuvant and maintenance
chemotherapy compared with standard care to improve
Acknowledgements We would like to thank all patients who participated in the
HRQoL and reduce CRF in patients with ovarian cancer BENITA study as well as Andrea Krull (Verein Eierstockkrebs Deutschland e.V.) for
and (2) to establish an exercise and nutrition programme her helpful advice on the study plan. The authors would also like to thank Professor
ready for implementation into routine clinical practice Dr S C Bischoff of the University Hohenheim for providing them with the validated
for patients with ovarian cancer. German version of the MEDAS questionnaire.
Contributors TM, JvG, SP, KHS, BS, B-CZ and JC-C contributed to study
Author affiliations conception and design. TM, MHB, JvG and ZS contributed to data and sample
1
Cancer Epidemiology, University Cancer Center Hamburg (UCCH), University collection. JC-C obtained funding for the pilot project. TM, MHB and JC-C drafted
Medical Center Hamburg-Eppendorf, Hamburg, Germany the first version of the manuscript. MHB is responsible for data management
2
Medical Biometry and Epidemiology, University Medical Center Hamburg- of pilot study. HB performed the sample size calculations and supervised
Eppendorf, Hamburg, Germany randomisation process. All authors revised the protocol critically for important
3
Department of Oncology, Hematology, BMT with Section Pneumology, Hubertus intellectual content and read and approved the final version of the protocol. JC-C
Wald Tumour Center, University Cancer Center Hamburg (UCCH), University Medical is guarantor.
Center Hamburg-Eppendorf, Hamburg, Germany
4 Funding The pilot phase of the BENITA study has been funded for 2 years by
Department of Gynaecology and Gynaecologic Oncology, University Medical Center
the Hamburger Krebsgesellschaft e.V. (grant number: not applicable). There is no
Hamburg-Eppendorf, Hamburg, Germany
5
Center for Athletic Medicine (UKE Athleticum), University Medical Center Hamburg- pharmaceutical industry funding and there are no commercial interests.
Eppendorf, Hamburg, Germany Competing interests None declared.

Open access
Patient and public involvement Patients and/or the public were involved in the 15 Thomson CA, Crane TE, Miller A, et al. A randomized trial of diet
design, or conduct, or reporting, or dissemination plans of this research. Refer to and physical activity in women treated for stage II-IV ovarian cancer:
the Methods section for further details. rationale and design of the lifestyle intervention for ovarian cancer
enhanced survival (lives): an NRG Oncology/Gynecologic Oncology
Patient consent for publication Not applicable. Group (GOG-225) study. Contemp Clin Trials 2016;49:181–9.
16 Stelten S, Hoedjes M, Kenter GG, et al. Rationale and study
Ethics approval This study involves human participants and was approved by The
protocol of the physical activity and dietary intervention in women
ethics committee of the Faculty of Medicine at Hamburg University approved the with ovarian cancer (Padova) study: a randomised controlled
study Participants gave informed consent to participate in the study before taking trial to evaluate effectiveness of a tailored exercise and dietary
part. intervention on body composition, physical function and fatigue in
Provenance and peer review Not commissioned; externally peer reviewed. women with ovarian cancer undergoing chemotherapy. BMJ Open
2020;10:e036854.
Data availability statement Data are available upon reasonable request. Data 17 Piercy KL, Troiano RP, Ballard RM, et al. The physical activity
cannot be made publicly available for legal reasons. Due to data privacy rules guidelines for Americans. JAMA 2018;320:2020–8.
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responsible scientific personnel at UKE, Hamburg, Germany within the framework of inventory (MFI) psychometric qualities of an instrument to assess
fatigue. J Psychosom Res 1995;39:315–25.
the respective research project. It is not permitted to give third parties access to the
19 Kondrup J, Rasmussen HH, Hamberg O, et al. Nutritional risk
data without a research proposal approved by the principal investigator. screening (NRS 2002): a new method based on an analysis of
Open access This is an open access article distributed in accordance with the controlled clinical trials. Clin Nutr 2003;22:321–36.
Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which 20 Wendel-Vos GCW, Schuit AJ, Saris WHM, et al. Reproducibility and
permits others to distribute, remix, adapt, build upon this work non-commercially, relative validity of the short questionnaire to assess health-enhancing
physical activity. J Clin Epidemiol 2003;56:1163–9.
and license their derivative works on different terms, provided the original work is
21 Agarwala P, Salzman SH. Six-Minute walk test: clinical role,
properly cited, appropriate credit is given, any changes made indicated, and the use technique, coding, and reimbursement. Chest 2020;157:603–11.
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Heiko Becher http://orcid.org/0000-0002-8808-6667 for monitoring cancer patients receiving chemotherapy and home
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Previous studies on postdiagnosis exercise in ovarian

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*T0 = baseline, T1=mid-­chemotherapy, T2=after completion of chemotherapy, T3=1-­year FU.

8 Maurer T, et al. BMJ Open 2022;12:e054091. doi:10.1136/bmjopen-2021-054091

Figure 2 Descriptive results of in-­person assessments at baseline (T0), mid-­chemotherapy (T1), after completion of

Maurer T, et al. BMJ Open 2022;12:e054091. doi:10.1136/bmjopen-2021-054091 9

10 Maurer T, et al. BMJ Open 2022;12:e054091. doi:10.1136/bmjopen-2021-054091

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*T0 = baseline, T1=mid-chemotherapy, T2=after completion of chemotherapy, T3=1-year FU.

Figure 2 Descriptive results of in-person assessments at baseline (T0), mid-chemotherapy (T1), after completion of