Pelvic Radiation Injuries After Cancer Treatment: Symptoms, Quality of Life and Experiences Before, Along and After Hyperbaric Oxygenation Treatment

Description:

Late effects following radiation of pelvic cancers:

Annually, more than 32000 Norwegians are diagnosed with cancer where approximately 70% will
be alive 5 years after diagnosis. About 50% of all cancer patients receive radiation as part
of their multimodal cancer treatment, and 50% of these will be long-term survivors.
Irradiation therapy is an essential part of the curative treatment of pelvic malignancies,
including rectal, uterine and cervical carcinoma. Although precautions and advances are
taken, radiation may affect surrounding healthy tissue and lead to acute or chronic radiation
injury. About 5-15% of the patients experience late radiation tissue injury (LRTI) that
develops months or years after radiation, characterized by poor microcirculation with
hypoxia, tissue damage and fibrosis. Consequently, frequent late-effects are related to
radiation cystitis, proctitis and enteritis, soft tissue necrosis (skin and vagina) and
fistulas with increased frequency, urgency and leakage of urine or faces, diarrhoea and pain.
Although these late- effects obviously interfere significantly with the survivors’ quality of
life (QOL) and psychosocial health, research regarding these consequences is extremely
limited.

Hyperbaric oxygen treatment (HBOT) for pelvic LRTI:

HBOT is a treatment modality where the patient is placed in a pressure chamber breathing 100%
oxygen while exposed to elevated ambient pressure. HBOT for pelvic LRTI typically involves a
treatment pressure of 2.4 ATA Atmospheres Absolute) while breathing oxygen once daily for
about 90 minutes for 6 weeks (about 30 ‘dives’ in total). HBOT for LRTI is based upon its
ability to increase tissue oxygenation, stimulate neoangiogenesis and cellular regeneration
and thereby induce revitalizing and healing of damaged tissue. Although HBOT is a time-
consuming treatment, it is well accepted and tolerated by the patients, with few and usually
harmless side effects.

Previous studies on the effect of HBOT to reduce pelvic LRTI have not yet yielded broadly
accepted and conclusive results. The available studies indicate that HBOT has a positive
effect on a variety of conditions, although some studies report no effect. A Cochrane review
concludes that HBOT may improve outcomes in various kinds of cancer related radiation
injuries (e.g. head and neck, proctitis, osteoradionecrosis), suggesting that other tissues
also are likely to respond (e.g. bladder). However, these studies operate with very
heterogeneous timepoints for follow-up, varying from right after HBOT is finished to several
weeks, months or years after, which may have influenced the outcomes. However, we could not
find any publication stating the course of symptomatic improvement for pelvic LRTI. This
knowledge-gap is a challenge when informing patients and handling their expectations for this
treatment.

QOL following HBOT:

Late-effects from cancer treatment, especially pelvic LRTI, may affect all parts of cancer
survivors’ life. Consequently, quality of life (QOL) is reckoned as an important outcome as
it comprises physiological, psychological and social aspects of well-being. However, there is
an evident research gap on how pelvic LRTI influences the patients’ QOL, as well as how these
outcomes develop in a longitudinal perspective. Two studies show QOL improvement in patients
with chronic diabetic foot ulcers after 6 weeks. One study found significant QOL improvements
from perioperative HBOT in the dimensions of pain, global health and dyspnoea in 66 patients
with head and neck cancers. Another study of 101 radiation-injured patients (54% head and
neck, 36 % intestine and 11% bladder) showed significant one-year improvements in the QOL
dimensions of vitality and physical-, role- and social function. A significantly improved
healing and increased bowel-specific QOL was found immediately after HBOT and at one-year
follow-up in a randomized controlled study of 120 patients with radiation proctitis. In
contrast, a systematic review state that no conclusion about HBOT’s influence on QOL can be
made.

In summing up, different outcomes of HBOT from pelvic radiation injured cancer survivors in a
longitudinal perspective are highly requested as the existing research comprises small
samples, has methodological limitations and yields scant results.

The study’s goals and research questions:

This study embraces three main goals: The primary goal is to improve knowledge on how QOL is
affected in survivors of pelvic cancer with LRTI, and how this may change due to HBOT. The
second goal is to gain information on the patients’ knowledge and expectations concerning
HBOT and their experiences and satisfaction with the care along the HBOT process. The third
goal is to improve knowledge on the longitudinal changes in LRTI symptoms and the patients’
long-term QOL after finishing HBOT. Consequently, this study addresses the following research
questions:

1. How do patients experience that the LRTI symptoms influence their everyday life?

2. What perceived information, knowledge and expectations concerning HBOT do patients
express before HBOT?

3. What are the patients’ self-reported LRTI burden,QOL and psychosocial health before
HBOT?

4. How do LRTI symptoms change during and after the HBOT course?

5. How do QOL and psychosocial health change during the HBOT course?

6. What is the correlation between LRTI symptoms and QOL during and after the HBOT process?

7. How do patients experience the HBOT process?

8. How satisfied with care are patients along the HBOT process, and which factors do they
describe as important for their satisfaction?

9. What are the patients’ long-term QOL, psychosocial health and LRTI burden after HBOT?

Study design:

Based on the research questions, we will perform a mixed methods study with a prospective
longitudinal embedded design. Mixed method is reckoned as the third research paradigm, and in
this design quantitative data are collected longitudinal (> 3 time-points) and qualitative
data are collected at two time points. This design is especially recommended where
randomization is not suited or possible, and because it draws on the strengths and
minimalizes the weaknesses of both quantitative and qualitative methods. Consequently, it may
yield a more complete and nuanced picture of the topic, as validated questionnaires provide
quantitative outcome data and in-depth interviews provide process data to explore and
elaborate the quantitative results.

Recruitment and eligibility criteria: The study will recruit participants from patients that
have been referred to HBOT and will undergo the treatment independently from the study.
Participation in the study will neither influence whether patients are treated with HBOT, nor
time or lengths or any other HBOT-related measure.

Data collection: see elsewhere

Analyses of data:

Quantitative analyses: Statistical tests will be two-tailed, with statistical significance
defined as P< .05. Descriptive statistics, correlations, paired T-tests, multiple regression analyses and longitudinal analysis with linear mixed models (LMM) (or the equvalent non-Parametric tests dependent of the characteristics of the final data set) will be used for analysis of change. Effect sizes will be calculated by Cohen's d, while Z tests will be performed to analyze differences between the sample mean and the mean in the general populations. Qualitative analysis: Systematic text condensation (STC) will be used to analyze qualitative data. This is a descriptive and exploratory method for thematic cross-case analysis of interviews. STC is a four-step analysis that includes 1) gaining a total impression; 2) identifying units of meaning; 3) abstracting the contents of individual units of meaning; 4) summarizing their importance. Ethics: The Regional Committee for Medical and Health Research Ethics in northern Norway has approved the project (2018/706). The study will be conducted in line with the Helsinki Declaration, providing the participants with oral and written information and written consent. As all participants will be treated with HBOT independent of inclusion in the study, we do not anticipate any negative outcomes for study-patients. Project management, organization and cooperation: This study is a cooperation between Center for Crisis Psychology (CCP), Faculty of Psychology, University of Bergen and Section for Hyperbaric Medicine (SHM), Department of Occupational Medicine (DOM), at Haukeland University Hospital in Bergen, Norway. A project group, chaired by CCP's research leader, May Hauken, will run the project. As HBOT represents a narrow field internationally, the study is connected to DOM's already existing international partners in the Nordic cooperation. Additionally, a multidisciplinary and international Advisory Board will be connected to the project. User involvement will be include throughout the study and include patients, representative from the Norwegian Gynecological Cancer Organization and health care professionals working with HBOT. Progress plan and dissemination of results: This is a 4 year project with a specific progress plan. Based on the research questions and collected data, we plan to publish at least 8 scientific papers in international peer-reviewed journals. Results will also be disseminated via lectures, popular scientific papers, national and international conferences. At the end of the project period, we will arrange a summing -up conference.

Condition:

Cancer

Treatment:

Hyperbaric oxygen treatment

Start Date:

August 6, 2018

Sponsor:

University of Bergen

For More Information:

https://clinicaltrials.gov/show/NCT03570229