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Hyperbaric oxygen treatment for late radiation-induced tissue toxicity in treated gynaecological cancer patients: a systematic review

This article has been updated

Abstract

Purpose

The aim of this study was to investigate the result of hyperbaric oxygen therapy (HBOT) in women with treated gynaecological malignancies who suffer from late radiation-induced tissue toxicity (LRITT). Moreover, which symptoms of LRITT benefit most from HBOT was evaluated as well.

Material and Methods

An online literature search was conducted using PubMed; Embase and the Cochrane Library. Studies were included if the study examined gynaecological cancer patients who had been treated with radiotherapy, who suffered from LRITT and who subsequently received HBOT. In addition, the outcome measures were based on examining the effects of HBOT.

Results

Twenty-one articles were included. The study investigating proctitis reported an improvement and three out of four studies investigating cystitis reported decreased complaints in women treated for gynaecological malignancies. In addition, all studies reported improvement in patients with wound complications and fifty percent of the studies reported better Patient Reported Outcome Measurements (PROMS) in women with gynaecological malignancies. Finally, all studies, except one related to pelvic malignancies reported reduced prevalence of symptoms for cystitis and proctitis and all studies reported better PROMS. However, only eleven studies reported p-values, nine of which were significant.

Conclusion

This study demonstrated that HBOT has a positive effect in women with gynaecological LRITT. Within the included patient group, gynaecological cancer patients with wound complications seem to benefit most from this treatment compared to other late side effects of LRITT.

Introduction

Worldwide, nearly 1.4 million women were diagnosed with gynaecological cancers in 2020 [1]. Due to aging populations and population growth in developed countries, this number will increase every year [2].

The gynaecological cancers included in this review are ovarian-, cervical-, vaginal-, uterine- and vulvar cancers. Gynaecological cancer patients are often treated using multimodality therapies, including surgery and radiotherapy or chemotherapy. Only in early stage gynaecological cancer patients, surgical treatment without adjuvant therapy is often sufficient [3,4,5,6]. In addition, radiotherapy is the standard treatment of vaginal cancer, as the cancer’s proximity to normal tissues limits its surgical options as a treatment for this type of cancer [7]. Radiotherapy as a component for the treatment of gynaecological malignancies has increased the local control of cervical-, uterine-, vulvar- and vaginal malignancies [8]. Although radiotherapy provides an increased chance of local control, it can also cause damage to surrounding organs and tissues [8]. This is referred to as late radiation-induced tissue toxicity (LRITT). LRITT can be described as damage to organs and tissues that occurs at least three months after radiotherapy has ended [9].

LRITT can arise through three underlying mechanisms whereby radiotherapy can damage both parenchymal and vascular cells. The first mechanism of oxidative damage to cells is caused by a local increase of reactive oxygen species (ROS) at the site of the tumor. As a result, these ROS also produce pro-inflammatory cytokines and chemokines that cause inflammation and ultimately tissue damage and cell death. Finally, radiotherapy can cause tissue damage and cell death via the innate immune response. This mechanism involves both bone marrow-derived cells and macrophages [10].

The average annual incidence of LRITT is 13.8% [11]. These late side effects of radiotherapy can be very diverse and present clinically as proctitis, cystitis or as necrosis and poor healing of wounds in the vaginal, vulvar and rectovaginal area.

One of the treatment modalities that could reduce or even cure complaints of LRITT is hyperbaric oxygen therapy (HBOT). LRITT is an internationally accepted indication for HBOT. This treatment implies creating a hyperbaric environment in which patients are being administered high oxygen concentrations. It uses a chamber in which the patient is administered 100% oxygen at a pressure ranging from 2.0 to 3.0 atmospheric pressure (ATA) for a duration of 60 to 120 min. Patients could be treated in monoplace chambers, in which one patient can be treated or multiplace chambers, in which multiple patients can be treated simultaneously [12].

The treatment effects of HBOT in LRITT are based on an increased systemic concentration of reactive oxygen species (ROS) and reactive nitrogen species (RNS), resulting in increased wound growth factors and a mobilization of stromal progenitor cells (SPc) from the bone marrow. As a result of these two processes, increased neovascularization will occur. In addition, the increased systemic concentrations of ROS and RNS cause neutrophil \(\upbeta\)-actin nitrosylation, reduced monocyte chemokine synthesis and changes in ischemic preconditioning. Subsequently, these processes result in a reduced inflammatory response and an improved post-ischemic tissue survival. All these processes result in a better neovascularization and wound healing. These pathways make HBOT clinically relevant for the treatment of LRITT [13].

The aim of this literature review was to investigate the result of HBOT in women with treated gynaecological malignancies who suffer from LRITT. This systematic review specifically investigated the effect of HBOT on various symptoms, which has not been done in previous studies.

Material and methods

Literature search

An online literature search was conducted in PubMed, Embase and the Cochrane Library on August 18, 2021. The included studies were published between 1992 and 2020. The main terms, along with many synonyms, used in the literature search in PubMed were: ‘hyperbaric oxygen therapy’; ‘gynecological’; and various types of gynaecological cancers. The terms used in the literature search in Embase were: ‘gynecological cancer’; ‘female genital tract cancer’; and ‘hyperbaric oxygen therapy’. Finally, the terms ‘hyperbaric oxygenation’; ‘hyperbaric oxygen therapy’; ‘gynecological cancer’ and ‘genital diseases’ were used in the literature search in the Cochrane Library. A detailed overview of the literature searches is described in Additional files 1, 2, 3.

Outcome measures

For this review, the Late Effects Normal Tissue Task Force–Subjective, Objective, Management, Analytic (LENT—SOMA) score and clinical outcome score were used as primary outcome measures as these were the most commonly used outcome measures in the included studies. The Expanded Prostate Index Composite (EPIC) score, Inflammatory Bowel Disease Questionnaire (IBDQ) rectal bleeding score and many other outcome measures were used as secondary outcome measures. The EPIC score is often used to determine symptoms after radiotherapy in prostate cancer patients but can also be used for other types of pelvic cancers, such as vulvar malignancies. The urology and bowel sections of the EPIC score are not specifically based on symptoms of prostate cancer but answer questions about side effects after radiotherapy in the pelvic region [14].

Study selection

All articles of the literature search have been screened for title and abstract by the first author. Potentially eligible articles that could be included based on their title and abstract, were screened in full text for further assessment. The heading ‘similar articles’ was searched in PubMed in order to find additional articles.

Inclusion criteria

Articles were selected based on multiple inclusion criteria: (1) the patients must have had gynaecological malignancies in the past and had been treated with radiotherapy, (2) the patients must be affected by late radiation-induced tissue toxicity (LRITT) and (3) the patients have been treated with hyperbaric oxygen therapy (HBOT).

Exclusion criteria

The exclusion criteria were: (1) the study was not published in English, (2) the study was not performed in humans, (3) articles that were not available, including abstract, were excluded and (4) case reports and case series were excluded.

Data extraction

Data such as study characteristics, patient characteristics, characteristics of HBOT and outcome measures were extracted. In addition, the time from radiation to injury, the time from injury to treatment and the time to follow-up have been reported. The comparison of the symptoms and the side effects of HBOT have also been extracted. Finally, the results and significance levels, if available, were reported. This also included Patient Reported Outcome Measures (PROMS), in which the quality of life, pain scores and depression symptoms were evaluated.

Statistical description

Data were presented on a descriptive manner. The outcomes were presented with the p-values, 95% confidence interval (95% CI) or standard deviation (SD). Some studies have used the odds ratio (OR) to present the effect of HBOT. Finally, some studies only reported percentages or the improvement of the symptoms.

Results

Study selection

We have found 226 articles through the PubMed search. 173 articles were found through the search in Embase and 18 articles were found through the search in the Cochrane Library. Subsequently, 198 articles were excluded from the PubMed search, 136 articles were excluded from the Embase search and 18 articles were excluded from the Cochrane Library search based on title and abstract. For detailed exclusion criteria, see Additional files 4, 5, 6. After this exclusion, 32 articles from the PubMed search were screened for full-text and 27 articles from the Embase search were screened for full-text. After we excluded 17 articles from the PubMed search based on full-text, 15 articles were ultimately included in this review. In the Embase search, 21 articles were excluded based on full-text after which 6 articles were ultimately included in this review. Finally, the total number of included studies was 21 [14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34]. For the detailed flow chart, see Fig. 1.

Fig. 1
figure 1

Flow chart of the literature search

Included studies

Study designs

Of the included 21 studies, different types of research designs were used by the researchers. Four studies were randomized controlled trials, one was a cohort study, twelve studies used a retrospective analysis and two studies used prospective analysis. In addition, one study was a combined retrospective and prospective observational study. One study did not report a study design or the study design could not be inferred. For a detailed overview, see Additional file 7.

Patient characteristics

A total of 1026 patients were included in these twenty-one studies, of which 531 patients had gynaecological cancers. The age of the patients varied widely with a range of seven to ninety-one years. For a detailed overview, see Table 1.

Table 1 Study and patient characteristics

Technical characteristics regarding HBOT

In Table 1, all information about the technical characteristics of hyperbaric oxygen therapy (HBOT) are reported. HBOT was used in all studies, with pressure varying from 2.0 to 3.0 atmospheric pressure (ATA). The number of sessions varied between 18 and 44. The time of the sessions was ninety minutes by default but could range from sixty to hundred-twenty minutes.

Time

The time between radiation and injury, the time between injury and therapy and the time to follow-up are reported in Additional file 8.

Outcome measures

Fifteen [17, 19,20,21,22,23,24,25,26, 29,30,31,32,33,34] out of twenty-one studies used clinical outcome measures. The Expanded Prostate Index Composite (EPIC) score was used in two studies [14, 16] and can be divided into a urinary and bowel domain. In addition, the Common Terminology Criteria for Adverse Events (CTCAE) scale has been used as a measure of gastrointestinal symptoms [15] and hematuria [32]. The Radiation Therapy Oncology Group (RTOG) criteria is based on the severity of the symptoms [27]. Finally, the LRMGS determines the Late Radiation Morbidity Grading Scheme.

Patient reported outcome measures

In addition to these outcome measures, the included studies used Patient Reported Outcome Measures (PROMS). The Late Effect Normal Tissues—Subjective Objective Management and Analytic (LENT—SOMA) score reflects the severity of the radiation induced problems and is represented by grades [35]. Jones 2006 [23] has not published or described the LENT-SOMA questionnaire and the questionnaires of the other studies differed. In addition, the 36-item Short Form (SF-36) scale and the Karnofsky score were used as the primary outcome for quality of life [16, 18]. The National Cancer Institute common toxicity criteria (NCI CTC) are related to the toxicity of tissues [22]. For a detailed overview of all outcome measures, see Table 1.

Difference of reported studies

Of all 21 included studies, 9 evaluated the treatment effects of HBOT on late radiation-induced tissue toxicity (LRITT) in gynaecological malignancies and 12 evaluated the effects of HBOT on LRITT in pelvic malignancies. As in the latter group it was not clearly reported where the primary tumour was located it was not possible to study the specific effects of HBOT on gynaecological malignancies. Therefore, both types of studies evaluating these different study populations are separately discussed below.

Results studies gynaecological malignancies

Table 2 shows all information about the results in the 9 studies investigating the gynaecological malignancies related to proctitis, cystitis, wound complications and PROMS.

Table 2 Results and significance level of gynaecological malignancies

Cystitis

Oliai 2012 [17], Parra 2011 [20], Safra 2008 [22] and Al-Ali 2010 [26] evaluated patients with cystitis who had suffered from gynaecological malignancies. Oliai 2012 [17] reported a mean reduction of the LENT-SOMA score of 0.89. In addition, Parra 2011 [20] reported a 100% complete resolution of macroscopic bleeding after HBOT. Safra 2008 [22] reported a 100% resolution of macroscopic hematuria and 3.0 points mean improvement of CTC change in cystitis (p = 0.001). Although three out of four studies reported an improvement in cystitis, only Safra 2008 [22] has reported p-values (p = 0.001). Al-Ali 2010 [26] reported no response to HBOT in the treatment group for hemorrhagic cystitis.

Proctitis and overall bowel symptoms

Safra 2008 [22] reported improvement in proctitis after HBOT. This study reported a significant 3.0 points mean improvement of CTC change in proctitis (p = 0.001) [22].

Wound complications

Safra 2008 [22], Williams 1992 [24], Feldmeier 1996 [25] and Fink 2006 [34] reported improvement in wound complications. Safra 2008 [22] reported 100% resolution of scar complications and 4.0 points mean improvement of the CTC change in wound healing complications (p = 0.001). In addition, Williams 1992 [24] reported a complete recovery or improvement of necrosis and fistulas in 92.9% of the patients. Feldmeier 1996 [25] reported a recovery from the injuries after HBOT in 61.3% of the patients. Finally, Fink 2006 [34] reported a complete healing of necrotic ulcers in 50% of the patients and a 50% improvement in 50% of the patients. Only Safra 2008 [22] reported a significant p-value (p = 0.001).

Patient reported outcome measures

Multiple studies have published PROMS, including quality of life, pain and depression symptoms. Sidik 2007 [18] reported a significant difference of 13.95% between the control group and the treatment group in the LENT-SOMA score (p = 0.008) and a difference of 12.80% in the Karnofsky score (p = 0.007) six months after HBOT. Rud 2009 [21] reported no improvement in the Brief Pain Inventory (BPI) score or Montgomery and Asberg Depression Rating Scale (MADRS) but fifty percent of the patients noticed some or good effect after treatment. This study did not report p-values at all.

Results studies pelvic radiotherapy

Twelve of the twenty-one studies included patients with LRITT after pelvic radiotherapy. For a detailed overview of these studies, see Table 3.

Table 3 Results and significance level of pelvic radiotherapy

Cystitis

Oscarsson 2013 [14], Oscarsson 2019 [16], Andren 2020 [28], Ngoo 2018 [29], Lin 2017 [30], Ribeiro de Oliveira 2015 [31], Mougin 2016 [32] and Ferreira 2014 [33] evaluated patients with cystitis who had suffered from pelvic malignancies. All studies reported an improvement in cystitis symptoms. Oscarsson 2013 [14] reported a significant improvement in the EPIC score in the urinary domain (p < 0.001). Secondly, Oscarsson 2019 [16] reported a significant improvement in the EPIC score (p = 0.013 and p = 0.0047) and LRMGS grades (p = 0.0012). In addition, Andren 2020 [28] reported a significant mean LENT-SOMA score reduction for cystitis of 3.7 (p < 0.001). Ngoo 2018 [29] reported a bleeding resolution in 77.8% of the patients and Lin 2017 [30] reported a resolution of macroscopic haematuria in 83.3% of the patients and a decrease of macroscopic haematuria in 7.1% of the patients. Moreover, Ribeiro de Oliveira 2015 [31] reported complete recovery from haematuria in 67% of the patients and a partially recovery from haematuria in 22.7% of the patients. Mougin 2016 [32] reported a complete resolution of haematuria in 52.1% of the patients and a partially resolution of haematuria in 12.7% of the patients. Finally, Ferreira 2014 [33] reported a response rate of haematuria resolution or haematuria improvement after a median follow-up period of 55.5 months of 91.4%. Ferreira 2014 [33] also reported a significant median difference in the sum of subjective LENT-SOMA scores before and after HBOT of 5 (p < 0.001). All studies except Lin 2017 [30] reported p-values. Ngoo 2018 [29], Ribeiro de Oliveira 2015 [31] and Mougin 2016 [32] only reported p-values of the results in subgroup analyses.

Proctitis and overall bowel symptoms

Glover 2016 [15] reported insignificant improvement in the Mann–Whitney U score (p = 0.50 and p = 0.092) and the Inflammatory Bowel Disease Questionnaire (IBDQ) rectal bleeding score (p = 0.12). This study also reported an insignificant improvement in the LENT-SOMA score (p = 0.11 and p = 0.16) and no differences in the CTCAE grades were found. Moreover, Oscarsson 2013 [14] and Oscarsson 2019 [16] reported a significant improvement in the EPIC score in the bowel domain with respectively a p-value < 0.001 and a 95% CI of 1.15 to 15.54. Clarke 2008 [19] reported a significant better improvement in the treatment group for the LENT-SOMA score with a difference of 2.39 points (p < 0.0001), a significant greater healing or improvement in the treatment group with a difference of 26.4% and a 32% risk reduction was found. Andren 2020 [28] reported a significant mean LENT-SOMA score reduction for proctitis of 3.8 (p = 0.004). Finally, Jones 2006 [23] reported an improvement in proctitis complaints, with no p-values reported.

Patient reported outcome measures

Bui 2004 [27] reported a 100% overall improvement in late side effects of pelvic radiotherapy, but no p-values have been reported. In addition, Oscarsson 2019 [16] reported a significant improvement in the mean SF-36 score for general health in the treatment group of 13.2 points (p = 0.0006).

Comparison of the symptoms

Within the included patient group, gynaecological cancer patients with wound complications benefit most from HBOT compared to other late side effects of LRITT with a range of 50%-100% resolution in three of the four studies. All four studies reported a marked improvement in patients with wound complications after HBOT.

Side effects

Fifteen studies [15,16,17, 19, 20, 23,24,25, 27,28,29, 31,32,33,34] reported adverse effects after HBOT and six studies [14, 18, 21, 22, 26, 30] did not report adverse effects after HBOT. In this study, the most reported adverse effects of HBOT were barotraumas or other complications in the ears, which is reported in fourteen studies. The calculated incidence of this symptom reported in these studies is approximately 1:10 [15,16,17, 19, 20, 23, 24, 27,28,29, 31,32,33,34]. In this review, the calculated percentage of patients with barotrauma or other complications in the ears was 10.3% and approximately corresponded to the study Blanshard 1996 [36]. A second common side effect reported in the included studies was myopia, or other complications in the eyes, with a calculated incidence of approximately 1:25 [15, 16, 19, 27, 28, 32]. A detailed overview of the side effects is presented in Additional file 9.

Discussion

This review demonstrated that HBOT is an effective and safe way to treat LRITT in women with treated gynaecological cancers in reported complaints of proctitis, cystitis, wound complications and Patient Reported Outcome Measures (PROMS). All but three studies [15, 21, 26] investigating LRITT reported a positive result after the HBOT. In addition, nine studies [14, 16, 18, 19, 22, 28, 29, 32, 33] reported significant p-values. A low incidence of adverse effects after HBOT has been reported.

Several studies had been published regarding the treatment effects of HBOT in patients with LRITT. Most studies conclude that HBOT has a positive effect on gynaecological patients with LRITT. This review is therefore consistent with previous systematic reviews such as Craighead 2011 [37] and Allen 2012 [11]. This systematic review specifically investigated the effect of HBOT on various symptoms of LRITT in patients with treated gynaecological malignancies, whereas previous studies have often examined one symptom such as cystitis only or proctitis only.

All studies except Al-Ali 2010 [26] reported positive results with regard to HBOT on cystitis complaints [17, 20, 22]. However, only one study [22] reported significant p-values which indicates a low validity. Four studies [14, 16, 28, 33] investigating the effect of HBOT on cystitis in pelvic radiotherapy, showed a significant positive effect of HBOT and two studies [29, 32] reported significant p-values in the subgroup analyses. Most studies have reported a positive effect, so patients with cystitis may benefit from HBOT.

Regarding proctitis as LRITT, all seven studies except Glover 2016 [15] reported positive effects. These studies focused either on gynaecological malignancies or on patients with pelvic radiation. From this it is demonstrated that patients with proctitis may benefit from HBOT.

All four studies that examined wound complications in the vaginal, vulvar and rectovaginal area in gynaecological malignancies reported a positive result. The range for complete resolution of scar complications, necrotic ulcers and the healing of injuries was 50%-100% in three studies [22, 25, 34]. However, only one study [22] reported a significant result. From these results it can be concluded that gynaecological patients with wound complications in these areas benefit most from HBOT compared to other late side effects of LRITT.

Finally, three of the four studies [16, 18, 27] investigating Patient Reported Outcome Measures (PROMS), including quality of life, pain and depression symptoms reported positive results in gynaecological malignancies and pelvic radiotherapy. Sidik 2007 [18] showed a significant difference between the control and treatment group, Bui 2004 [27] reported a hundred percent overall improvement and Oscarsson 2019 [16] reported an improvement in mean SF-36 score for general health of 13.2 points. Therefore, it can be concluded that in most patients the quality of life, pain and depression symptoms improved after HBOT.

The main strength of this review was the fact that different symptoms of LRITT were compared with each other, which has not been done in previous studies.

However, an important limitation of this review is the low quality of the included studies. Although there appears to be a benefit in treating gynaecological cancer patients suffering from LRITT with HBOT, few studies have reported significance, studies included few patients, studies published descriptive results, and different outcome measures were used in the included studies, making the studies difficult to compare. Because of this low quality of the included studies and the difficulty to compare the studies, the conclusion that HBOT offers a benefit in gynaecological cancer patients who suffer from LRITT should be taken with care.

Only Ferreira 2014 [33] reported patients experiencing vaginitis. The effect of HBOT on sexual disfunction due to radiotherapy will require further investigation in future studies, as pelvic radiotherapy plays a significant negative role in sexual dysfunction [38]. Ideally, more high-quality studies should be done to be included in a future review in order to improve the reliability of the study results. Moreover, the long-term effect could be evaluated in future research, as most included studies reported a follow-up period of two years or less.

Conclusion

From this review it can be concluded that the hyperbaric oxygen therapy (HBOT) has a positive effect on late radiation-induced tissue toxicity (LRITT) in gynaecological malignancies. Within the included patient group, gynaecological patients with wound complications localized in the vaginal, vulvar and rectovaginal area benefit most from this treatment compared to other late side effects of LRITT. The hyperbaric oxygen therapy can therefore be used in women who suffer from LRITT three months after their radiation for gynaecological cancers has ended. However, an important limitation of this review is the low quality of the included studies.

Future studies should be of higher quality in order to improve the reliability of obtained evidence so far. Moreover, the long-term effect of HBOT on LRITT in treated gynaecological malignancies should be investigated in subsequent studies. Future studies should also investigate the effect of HBOT on sexual disfunction in treated gynaecological cancer patients. Finally, future studies could further investigate the effect of HBOT on the quality of life in treated gynaecological cancer patients by using the European Organization for Research on Treatment of Cancer (EORTC) questionnaires.

Availability of data and materials

All data generated or analysed during this study are included in this published manuscript.

Change history

  • 06 November 2022

    After publication of the original article, the authors reported that the link in the pdf file to the Supplementary information was wrong. The article has been updated to correct this.

Abbreviations

HBOT:

Hyperbaric oxygen therapy

LRITT:

Late radiation-induced tissue toxicity

PROMS:

Patient reported outcome measures

ATA:

Atmospheric pressure

ROS:

Reactive oxygen species

RNS:

Reactive nitrogen species

SPc:

Stromal progenitor cells

LENT-SOMA:

Late effects normal tissue task force–subjective, objective, management, analytic

EPIC:

Expanded prostate index composite

IBDQ:

Inflammatory bowel disease questionnaire

CI:

Confidence interval

SD:

Standard deviation

OR:

Odds ratio

CTCAE:

Common terminology criteria for adverse events

RTOG:

Radiation therapy oncology group

LRMGS:

Late radiation morbidity grading scheme

SF-36:

36-Item short form

NCI CTC:

National cancer institute common toxicity criteria

BPI:

Brief pain inventory

MADRS:

Montgomery and asberg depression scale

EORTC:

European organization for research on treatment of cancer

References

  1. International Agency for Research on Cancer World Health Organization. Estimated number of new cases in 2020, worldwide, females, all ages. https://gco.iarc.fr/today/online-analysis-table?v=2020&mode=cancer&mode_population=continents&population=900&populations=900&key=asr&sex=2&cancer=39&type=0&statistic=5&prevalence=0&population_group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&group_cancer=1&include_nmsc=1&include_nmsc_other=1. Accessed June 30th.

  2. Australian Institute of Health and Welfare & Cancer Australia 2012. Gynaecological cancers in Australia: an overview. Cancer series no.70. Cat. no. CAN 66. Canberra: Australian Institute of Health and Welfare; 2012.

  3. Hill EK. Updates in cervical cancer treatment. Clin Obstet Gynecol. 2020;63(1):3–11. https://doi.org/10.1097/GRF.0000000000000507.

    Article  PubMed  Google Scholar 

  4. Orr B, Edwards RP. Diagnosis and treatment of ovarian cancer. Hematol Oncol Clin North Am. 2018;32(6):943–64. https://doi.org/10.1016/j.hoc.2018.07.010.

    Article  PubMed  Google Scholar 

  5. Fung-Kee-Fung M, Dodge J, Elit L, Lukka H, Chambers A, Oliver T, et al. Follow-up after primary therapy for endometrial cancer: a systematic review. Gynecol Oncol. 2006;101(3):520–9. https://doi.org/10.1016/j.ygyno.2006.02.011.

    Article  PubMed  Google Scholar 

  6. Rogers LJ, Cuello MA. Cancer of the vulva. Int J Gynecol Obstet. 2018;143(Suppl 2):4–13. https://doi.org/10.1002/ijgo.12609.

    Article  Google Scholar 

  7. Jhingran A. Updates in the treatment of vaginal cancer. Int J Gynecol Cancer. 2022;32(3):344–51. https://doi.org/10.1136/ijgc-2021-002517.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Cohen JG, Chang AJ. Use of stereotactic body radiotherapy in gynecologic cancers: local control with systemic treatment implications. Gynecol Oncol. 2020;159(3):599–600. https://doi.org/10.1016/j.ygyno.2020.11.002.

    Article  PubMed  Google Scholar 

  9. Azria D, Betz M, Bourgier C, Jeanneret Sozzi W, Ozsahin M. Identifying patients at risk for late radiation-induced toxicity. Crit Rev Oncol Hematol. 2012;84(Suppl 1):e35-41. https://doi.org/10.1016/j.critrevonc.2010.08.003.

    Article  PubMed  Google Scholar 

  10. Kim JH, Jenrow KA, Brown SL. Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials. Radiat Oncol J. 2014;32(3):103–15. https://doi.org/10.3857/roj.2014.32.3.103.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Allen S, Kilian C, Phelps J, Whelan HT. The use of hyperbaric oxygen for treating delayed radiation injuries in gynecologic malignancies: a review of literature and report of radiation injury incidence. Support Care Cancer. 2012;20(10):2467–72. https://doi.org/10.1007/s00520-012-1379-x.

    Article  PubMed  Google Scholar 

  12. Moon RE, Bakker D, Barnes R, Bennett M, Camporesi E, Cianci P, et al. Hyperbaric oxygen therapy indications. 14th ed. North Palm Beach, Florida 33408: Best Publishing Company; 2019.

  13. Camporesi EM, Bosco G. Mechanisms of action of hyperbaric oxygen therapy. Undersea Hyperb Med. 2014;41(3):247–52.

    PubMed  Google Scholar 

  14. Oscarsson N, Arnell P, Lodding P, Ricksten S, Seeman-Lodding H. Hyperbaric oxygen treatment in radiation-induced cystitis and proctitis: a prospective cohort study on patient-perceived quality of recovery. Int J Radiat Oncol Biol Phys. 2013;87(4):670–5. https://doi.org/10.1016/j.ijrobp.2013.07.039.

    Article  CAS  PubMed  Google Scholar 

  15. Glover M, Smerdon GR, Andreyev HJ, Benton BE, Bothma P, Firth O, et al. Hyperbaric oxygen for patients with chronic bowel dysfunction after pelvic radiotherapy (HOT2): a randomised, double-blind, sham-controlled phase 3 trial. Lancet Oncol. 2016;17(2):224–33. https://doi.org/10.1016/S1470-2045(15)00461-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Oscarsson N, Müller B, Rosén A, Lodding P, Mölne J, Giglio D, et al. Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): a randomised, controlled, phase 2–3 trial. Lancet Oncol. 2019;20(11):1602–14. https://doi.org/10.1016/S1470-2045(19)30494-2.

    Article  PubMed  Google Scholar 

  17. Oliai C, Fisher B, Jani A, Wong M, Poli J, Brady LW, et al. Hyperbaric oxygen therapy for radiation-induced cystitis and proctitis. Int J Radiat Oncol Biol Phys. 2012;84(3):733–40. https://doi.org/10.1016/j.ijrobp.2011.12.056.

    Article  CAS  PubMed  Google Scholar 

  18. Sidik S, Hardjodisastro D, Setiabudy R, Gondowiardjo S. Does hyperbaric oxygen administration decrease side effect and improve quality of life after pelvic radiation? Acta Med Indones. 2007;39(4):169–73.

    PubMed  Google Scholar 

  19. Clarke RE, Tenorio LMC, Hussey JR, Toklu AS, Cone DL, Hinojosa JG, et al. Hyperbaric oxygen treatment of chronic refractory radiation proctitis: a randomized and controlled double-blind crossover trial with long-term follow-up. Int J Radiat Oncol Biol Phys. 2008;72(1):134–43. https://doi.org/10.1016/j.ijrobp.2007.12.048.

    Article  CAS  PubMed  Google Scholar 

  20. Parra C, Gómez R, Marchetti P, Rubio G, Felmer A, Castillo OA, et al. Management of hemorrhagic radiation cystitis with hyperbaric oxygen therapy. Actas Urol Esp. 2011;35(3):175–9. https://doi.org/10.1016/j.acuro.2010.09.006.

    Article  CAS  PubMed  Google Scholar 

  21. Rud AK, Bjørgo S, Kristensen GB, Kongsgaard UE. Hyperbaric oxygen therapy for late radiation tissue injury in gynaecological patients. Support Care Cancer. 2009;17(12):1517–21. https://doi.org/10.1007/s00520-009-0619-1.

    Article  PubMed  Google Scholar 

  22. Safra T, Gutman G, Fishlev G, Soyfer V, Gall N, Lessing JB, et al. Improved quality of life with hyperbaric oxygen therapy in patients with persistent pelvic radiation-induced toxicity. Clin Oncol (R Coll Radiol). 2008;20(4):284–7. https://doi.org/10.1016/j.clon.2007.12.005.

    Article  CAS  Google Scholar 

  23. Jones K, Evans AW, Bristow RG, Levin W. Treatment of radiation proctitis with hyperbaric oxygen. Radiother Oncol. 2006;78(1):91–4. https://doi.org/10.1016/j.radonc.2005.11.004.

    Article  CAS  PubMed  Google Scholar 

  24. Williams JA Jr, Clarke D, Dennis WA, Dennis EJ 3rd, Smith ST. The treatment of pelvic soft tissue radiation necrosis with hyperbaric oxygen. Am J Obstet Gynecol. 1992;167(2):412–5. https://doi.org/10.1016/s0002-9378(11)91421-5.

    Article  PubMed  Google Scholar 

  25. Feldmeier JJ, Heimbach RD, Davolt DA, Court WS, Stegmann BJ, Sheffield PJ. Hyperbaric oxygen an adjunctive treatment for delayed radiation injuries of the abdomen and pelvis. Undersea Hyperb Med. 1996;23(4):205–13.

    CAS  PubMed  Google Scholar 

  26. Al-Ali BM, Trummer H, Shamloul R, Zigeuner R, Pummer K. Is treatment of hemorrhagic radiation cystitis with hyperbaric oxygen effective? Urol Int. 2010;84(4):467–70. https://doi.org/10.1159/000296289.

    Article  Google Scholar 

  27. Bui Q, Lieber M, Withers HR, Corson K, van Rijnsoever M, Elsaleh H. The efficacy of hyperbaric oxygen therapy in the treatment of radiation-induced late side effects. Int J Radiat Oncol Biol Phys. 2004;60(3):871–8. https://doi.org/10.1016/j.ijrobp.2004.04.019.

    Article  CAS  PubMed  Google Scholar 

  28. Andren J, Bennett MH. An observational trial to establish the effect of hyperbaric oxygen treatment on pelvic late radiation tissue injury due to radiotherapy. Diving Hyperb Med. 2020;50(3):250–5. https://doi.org/10.28920/dhm50.3.250-255.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Ngoo KS, Panicker D. The utility of hyperbaric oxygen therapy in managing haemorrhagic radiation-induced cystitis. Int J Urol. 2018;25(1):311.

    Google Scholar 

  30. Lin KH, Lee HC, Huang WS, Huang PW, Ke SC, Lee MG. Hyperbaric oxygen therapy for hemorrhagic radiation cystitis. Formos J Surg. 2017;50(2):52–6.

    Article  Google Scholar 

  31. Ribeiro de Oliveira TM, Romão AJC, Guerreiro FMG, Lopes TMM. Hyperbaric oxygen therapy for refractory radiation-induced hemorrhagic cystitis. Int J Urol. 2015;22(10):962–6. https://doi.org/10.1111/iju.12857.

    Article  CAS  PubMed  Google Scholar 

  32. Mougin J, Souday V, Martin F, Azzouzi AR, Bigot P. Evaluation of hyperbaric oxygen therapy in the treatment of radiation-induced hemorrhagic cystitis. Urology. 2016;94:42–6. https://doi.org/10.1016/j.urology.2016.04.015.

    Article  PubMed  Google Scholar 

  33. Ferreira C, Reis F, Correia T, Cardoso A, Cerquiera M, Almeida M, et al. Hyperbaric oxygen for long-term complications of radiation cystitis. J Radiother Pract. 2014;14(1):18–26. https://doi.org/10.1017/S1460396914000375.

    Article  Google Scholar 

  34. Fink D, Chetty N, Lehm JP, Marsden DE, Hacker NF. Hyperbaric oxygen therapy for delayed radiation injuries in gynecological cancers. Int J Gynecol Cancer. 2006;16(2):638–42. https://doi.org/10.1111/j.1525-1438.2006.00388.x.

    Article  CAS  PubMed  Google Scholar 

  35. Routledge JA, Burns MP, Swindell R, Khoo VS, West CML, Davidson SE. Evaluation of the LENT-SOMA scales for the prospective assessment of treatment morbidity in cervical carcinoma. Int J Radiat Oncol Biol Phys. 2003;56(2):502–10. https://doi.org/10.1016/s0360-3016(02)04578-9.

    Article  PubMed  Google Scholar 

  36. Blanshard J, Toma A, Bryson P, Williamson P. Middle ear barotrauma in patients undergoing hyperbaric oxygen therapy. Clin Otolaryngol Allied Sci. 1996;21(5):400–3. https://doi.org/10.1046/j.1365-2273.1996.00813.x.

    Article  CAS  PubMed  Google Scholar 

  37. Craighead P, Shea-Budgell MA, Nation J, Esmail R, Evans AW, Parliament M, et al. Hyperbaric oxygen therapy for late radiation tissue injury in gynecologic malignancies. Curr Oncol. 2011;18(5):220–7. https://doi.org/10.3747/co.v18i5.767.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Incrocci L, Jensen PT. Pelvic radiotherapy and sexual function in men and women. J Sex Med. 2013;10(Suppl 1):53–64. https://doi.org/10.1111/jsm.12010.

    Article  CAS  PubMed  Google Scholar 

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NIG, RAH, MLR and DNT all contributed to the design of the manuscript, the interpretation of the results and the data extraction from all included studies. All authors have read and approved the final manuscript.

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Supplementary Information

Additional file 1.

Table 4. Literature search in PubMed.

Additional file 2.

Table 5. Literature search in Embase.

Additional file 3.

Table 6. Literature search in the Cochrane Library.

Additional file 4.

Table 7. Reasons of exclusion from PubMed search.

Additional file 5.

Table 8. Reasons of exclusion from Embase search.

Additional file 6.

Table 9. Reasons of exclusion from the Cochrane library search.

Additional file 7.

Table 10. Study design of the included studies.

Additional file 8.

Table 11. Time.

Additional file 9.

Table 12. Reported side effects.

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Geldof, N.I., van Hulst, R.A., Ridderikhof, M.L. et al. Hyperbaric oxygen treatment for late radiation-induced tissue toxicity in treated gynaecological cancer patients: a systematic review. Radiat Oncol 17, 164 (2022). https://doi.org/10.1186/s13014-022-02067-6

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