Long-Term Patient-Reported Outcomes of Hyperbaric Oxygen Therapy for Haematuria Due to Radiation Cystitis Secondary to External Beam Radiotherapy for Pelvic Malignancy

Radiation proctitis and radiation cystitis are major complications for patients with cervical carcinoma following radiotherapy. In the present study, we aimed to determine the potential risk factors for the development of radiation proctitis and radiation cystitis after irradiation. A total of 1,518 patients with cervical carcinoma received external beam radiotherapy (EBRT) followed by high-dose-rate intracavitary brachytherapy (HDRICB) in our hospital. The incidences of radiation proctitis and radiation cystitis were recorded and associations with different factors (age, time period, tumor stage) were analyzed with χ2 (chi-squared) and Fisher exact tests. We found that 161 and 94 patients with cervical carcinoma were diagnosed with radiation proctitis and radiation cystitis, respectively, following radiotherapy. The prevalence of Grade I-II radiation proctitis or radiation cystitis was significantly lower than that of Grade III (radiation proctitis: 3.82% vs. 6.76%, P <0.05; radiation cystitis: 2.31% vs. 3.87%, P < 0.05) and was significantly enhanced in patients with late stage (IIIb) tumor progression compared to those in early stage (Ib, IIa) (P < 0.05). Moreover, the incidence of radiation proctitis and cystitis was not correlated with age or, time period following radiation, for each patient (P > 0.05). These observations indicate that a late stage of tumor progression is a potential risk factor for the incidence of radiation proctitis and cystitis in cervical carcinoma patients receiving radiotherapy.

To assess the effect of hyperbaric oxygen (HBO) therapy on radiation cystitis, clinical and histopathological characteristics were examined. Three women with radiation cystitis were treated with HBO therapy. Macrohaematuria was arrested in all patients. Cystoscopy demonstrated abnormal telangiectasia and inflammatory mucosa before treatment. After HBO therapy, the inflammatory mucosae were healed. However, abnormal vessels did not completely disappear. Histopathologically, the epithelium was atrophic and dilated lymph vessels and inflammatory cells were seen in the submucosa. These changes improved after treatment. HBO therapy is effective against radiation cystitis. With improvement of the clinical symptoms also the cystoscopic and histopathological findings changed favourably.

Hyperbaric Oxygen Treatment in Radiation-Induced Cystitis and Proctitis: A Prospective Cohort Study on Patient-Perceived Quality of Recovery

PD19-12 PATIENT REPORTED OUTCOME MEASURES FOLLOWING HYPERBARIC OXYGEN THERAPY FOR RADIATION CYSTITIS

The present study assessed the efficacy of hyperbaric oxygen therapy in reducing symptoms of radiation cystitis, a specific type of iatrogenic injury to the bladder, by systematic review of recent literature. The MEDLINE, Embase and Web of Science databases were searched using combinations of the terms "radiation," "cystitis" and "hyperbaric oxygen" to identify articles evaluating patients with radiation cystitis, treated with hyperbaric oxygen therapy. Only recent (≤10years) original studies were included. Data were extracted and pooled in order to calculate descriptive weighted averages. Articles were evaluated on their level of evidence. A total of 20 papers were obtained, resulting in a cohort of 815 patients who were treated with hyperbaric oxygen therapy for radiation cystitis. Overall and complete response rates varied from 64.8% to 100% and 20% to 100%, respectively. The weighted average overall and complete response rates were 87.3% and 65.3%, respectively. Adverse events were observed in 9.6% of the patients, but permanent side-effects were rare. The most prominent limitations were high cost and low availability. Hyperbaric oxygen therapy is effective in the treatment of radiation-induced cystitis, with minimal adverse events, but low availability and high cost. At present, evidence is low; therefore, more prospective studies are required.

Hyperbaric oxygen therapy for hemorrhagic radiation cystitis

This is the third update of the original Cochrane Review published in July 2005 and updated previously in 2012 and 2016. Cancer is a significant global health issue. Radiotherapy is a treatment modality for many malignancies, and about 50% of people having radiotherapy will be long-term survivors. Some will experience late radiation tissue injury (LRTI), developing months or years following radiotherapy. Hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for LRTI based on the ability to improve the blood supply to these tissues. It is postulated that HBOT may result in both healing of tissues and the prevention of complications following surgery and radiotherapy. To evaluate the benefits and harms of hyperbaric oxygen therapy (HBOT) for treating or preventing late radiation tissue injury (LRTI) compared to regimens that excluded HBOT. We used standard, extensive Cochrane search methods. The latest search date was 24 January 2022. We included randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing. We used standard Cochrane methods. Our primary outcomes were 1. survival from time of randomisation to death from any cause; 2. complete or substantial resolution of clinical problem; 3. site-specific outcomes; and 4. Our secondary outcomes were 5. resolution of pain; 6. improvement in quality of life, function, or both; and 7. site-specific outcomes. We used GRADE to assess certainty of evidence. Eighteen studies contributed to this review (1071 participants) with publications ranging from 1985 to 2022. We added four new studies to this updated review and evidence for the treatment of radiation proctitis, radiation cystitis, and the prevention and treatment of osteoradionecrosis (ORN). HBOT may not prevent death at one year (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.47 to 1.83; I2 = 0%; 3 RCTs, 166 participants; low-certainty evidence). There is some evidence that HBOT may result in complete resolution or provide significant improvement of LRTI (RR 1.39, 95% CI 1.02 to 1.89; I2 = 64%; 5 RCTs, 468 participants; low-certainty evidence) and HBOT may result in a large reduction in wound dehiscence following head and neck soft tissue surgery (RR 0.24, 95% CI 0.06 to 0.94; I2 = 70%; 2 RCTs, 264 participants; low-certainty evidence). In addition, pain scores in ORN improve slightly after HBOT at 12 months (mean difference (MD) -10.72, 95% CI -18.97 to -2.47; I2 = 40%; 2 RCTs, 157 participants; moderate-certainty evidence). Regarding adverse events, HBOT results in a higher risk of a reduction in visual acuity (RR 4.03, 95% CI 1.65 to 9.84; 5 RCTs, 438 participants; high-certainty evidence). There was a risk of ear barotrauma in people receiving HBOT when no sham pressurisation was used for the control group (RR 9.08, 95% CI 2.21 to 37.26; I2 = 0%; 4 RCTs, 357 participants; high-certainty evidence), but no such increase when a sham pressurisation was employed (RR 1.07, 95% CI 0.52 to 2.21; I2 = 74%; 2 RCTs, 158 participants; high-certainty evidence). These small studies suggest that for people with LRTI affecting tissues of the head, neck, bladder and rectum, HBOT may be associated with improved outcomes (low- to moderate-certainty evidence). HBOT may also result in a reduced risk of wound dehiscence and a modest reduction in pain following head and neck irradiation. However, HBOT is unlikely to influence the risk of death in the short term. HBOT also carries a risk of adverse events, including an increased risk of a reduction in visual acuity (usually temporary) and of ear barotrauma on compression. Hence, the application of HBOT to selected participants may be justified. The small number of studies and participants, and the methodological and reporting inadequacies of some of the primary studies included in this review demand a cautious interpretation. More information is required on the subset of disease severity and tissue type affected that is most likely to benefit from this therapy, the time for which we can expect any benefits to persist and the most appropriate oxygen dose. Further research is required to establish the optimum participant selection and timing of any therapy. An economic evaluation should also be undertaken.

297 Background: Although RC is a potentially significant acute and/or chronic complication of radiotherapy to the pelvic area (15-20% incidence), there is limited information about how it is managed in practice. Methods: The BUG membership (comprising of consultant Uro-oncologists) was surveyed as to their perception on and management of RC. Results: 87% (45/52) of respondents supervise radiotherapy to the bladder/pelvis. Of these 45, most consider acute RC during or immediately after treatment a significant problem in ‘some' (56%) or the ‘majority' (11%) of cases (‘minority': 33%). Late RC was mostly considered a significant problem in the ‘minority' of cases (73%), with the rest feeling it was a significant problem in ‘some' cases (27%). During radiotherapy or at follow-up the majority ‘always' (22%) or ‘sometimes' (60%) record the grade of cystitis (‘never': 18%). 93% do not have local guidelines for managing RC. The treatments most frequently used to treat acute RC are: fluids (71%); cranberry juice (36%); analgesia (36%); non-steroidal anti-inflammatory drugs (NSAIDs; 29%); and anti-spasmodics (18%). Mild late RC is treated similarly (fluids: 29%; analgesia: 22%; cranberry juice: 18%; NSAIDs: 16%), although 20% might consider no treatment. For moderate/severe late RC, most refer to an urologist (64%), with grade ≥2 cases, those with haemorrhagic cystitis (20%), and symptoms &gt;90 days post-radiotherapy (18%) being the most common reasons for referral. For those treating moderate/severe late RC, hyperbaric oxygen (38%), fluids (19%), and analgesia (19%) are most commonly used. Over half were not aware of alternative treatment options including mesna (69% not aware), sodium hyaluronate (62%), intravesical prostaglandin E1/E2 (62%), sodium pentosanpolysulphate (60%), or intravesical formalin (51%). All supported the development of national guidelines in collaboration with the British Association of Urological Surgeons and British Association of Urology Nurses. Conclusions: RC is acknowledged as a potentially significant issue, and, with the majority of cases managed by oncology, there is a recognised need for further guidance on optimal treatment and BUG has started this work.

This issue deals with a wide range of clinical topics of urology, and contains three Review Articles, seven Original Articles and one Urological Note. Radiation cystitis is a specific type of iatrogenic injury to the bladder. Radiation cystitis can be a complication of radiation doses starting from 45 to 55 Gy, and the risk increases significantly at cumulative doses of ≥60 Gy. It is a potential, but often intractable, complication of pelvic radiation therapy for treatment of pelvic malignancies. Villeirs et al. (Ghent, Belgium) assessed the efficacy of hyperbaric oxygen therapy in reducing symptoms of radiation cystitis by systematic review of recent literature. Hyperbaric oxygen therapy was effective (the weighted average overall and complete response rates were 87.3% and 65.3%, respectively) in the treatment of radiation-induced cystitis, with minimal adverse events, but low availability and high cost. At present, as evidence is low, more prospective studies seem to be required. The term, bacillus Calmette–Guerin (BCG) failure, is ambiguous, and includes a very heterogeneous population of patients. By strictly focusing on patients who are unlikely to benefit from additional BCG therapy and who need to be treated with radical cystectomy, the new concept of “BCG unresponsive” was recently proposed. Kikuchi et al. (Kanagawa, Japan) demonstrated the definition of BCG unresponsive, and assessed the development of novel therapeutic options for BCG unresponsive disease. So far, the blockade of the programmed cell death-1/programmed cell death-ligand 1 pathway, which is considered to be activated by BCG therapy, is promising. Furthermore, clinical trials with other strategies, such as vaccines, gene therapy, and targeted and cytotoxic therapies, are ongoing. It is well known that cisplatin has various toxicities, including myelosuppression, gastrotoxicity and ototoxicity, and the main dose-limiting side-effect is nephrotoxicity. Shiraishi et al. (Kyoto, Japan) evaluated the safety and efficacy of the combined regimen of paclitaxel and ifosfamide plus nedaplatin for patients with refractory or relapsed germ cell tumors and impaired renal function. Their results showed that paclitaxel, ifosfamide and nedaplatin chemotherapy can be considered a safe and effective (overall response rate: 60%) regimen that results in less nephrotoxicity in germ cell tumor patients with renal dysfunction. In patients who show prostate-specific antigen failure after external beam radiotherapy for local or locally advanced prostate cancer, salvage therapy targeting the prostate is currently an option. Yamada et al. (Kyoto, Japan) examined the effect of permanent salvage brachytherapy in prostate cancer patients suffering recurrence after three-dimensional conformal external beam radiotherapy. Permanent salvage brachytherapy was carried out in 13 patients who suffered prostate-specific antigen failure. Their results showed that targeted fusion biopsy-based three-dimensional cancer mapping should be used for permanent salvage brachytherapy treatment planning to reduce the incidence of treatment-related adverse events while maintaining good oncological outcomes. In contrast, Takeda et al. (New York, USA) examined a set of proposed eligibility factors for hemi-ablative focal therapy in prostate cancer, and determined the likelihood of residual extensive disease. Hemi-ablative focal therapy, which involves ablation of an entire half of the prostate, is most frequently carried out now. They retrospectively analyzed data from 98 patients with the focal therapy consensus meeting the inclusion criteria who underwent radical prostatectomy. Their results showed that an important number of patients meeting the focal therapy consensus meeting the inclusion criteria can present extensive disease. Interestingly, their study also implied that targeted biopsies might provide more accurate information about the selection of focal therapy candidates. Until recently, there has been only limited information about the clinicopathological features of malignant urachal tumors (MUTs) from a large population-based study. Nagumo et al. (Ibaraki, Japan) used the hospital-based cancer registry data to extract 456 MUT cases. Their results showed that MUTs are quite rare (0.4% of all malignant bladder cancers) in Japan, and most of those without metastasis are likely to be treated with surgery alone, even at advanced stages. The necessity of establishing a standard of care for MUT patients at advanced stages or with metastasis is also reported. None declared.

Hyperbaric oxygen – an effective tool to treat radiation morbidity in prostate cancer

HYPERBARIC OXYGEN THERAPY FOR RADIATION INDUCED HEMORRHAGIC CYSTITIS

The purpose of this paper was to provide an evidence-based evaluation of the safety and effectiveness of hyperbaric oxygen therapy (HBOT) for the treatment of non-neurological soft tissue radiation-related injuries (STRI). Systematic searches of medical bibliographic databases, the Internet, and lists of references were conducted in December 2010 and April 2013 to identify relevant primary studies. Inclusion and classification of papers was resolved through the application of a predetermined protocol. Information on both the safety and effectiveness of HBOT was analyzed. Forty-one articles were included, with 11 comparing HBOT to a regimen without HBOT. Comparative evidence varied considerably in methodological quality, and numerous limitations were identified. Absolute data showed that serious adverse events after HBOT were rare, while more common adverse events were minor and self-limiting. Compared to observation, conventional, or sham therapies, evidence of benefit in clinical outcomes was shown for HBOT for radiation proctitis and wounds in irradiated soft tissue of the head and neck, but not for postirradiation soft tissue edema or radiation cystitis. Clinical outcomes differed little between HBOT and argon plasma coagulation for radiation proctitis and between HBOT and hyaluronic acid for radiation cystitis. HBOT is a safe intervention which may offer clinical benefits to patients suffering from radiation proctitis and non-neurological STRI of the head and neck. However, differing clinical responses across STRI demonstrate a need for further well-designed clinical trials to validate the use of HBOT for individual STRI, both as an adjunct to conventional treatments and relative to definitive treatments.

e24043 Background: Radiation therapy remains a critical modality in the treatment of various cancers, but it often leads to adverse effects in surrounding tissues and organs. These side effects may manifest months after treatment and commonly involve the skin, gastrointestinal tract, and urinary system, resulting in inflammation, fibrosis, and pain. Hyperbaric Oxygen Therapy (HBO2) is a treatment option that has shown potential in mitigating these side effects by promoting angiogenesis, reducing inflammation, and decreasing fibrosis. This retrospective study evaluates the impact of HBO2 treatments on the quality of life (QoL) in patients with radiation-induced tissue damage. Methods: We analyzed the quality of life in 40 patients who received HBO2 for radiation-induced injuries, including radiation cystitis (n = 22), head and neck radiation injury (n = 13), and other radiation-related complications (n = 5). Two validated surveys were used: the Rand Corporation's SF-36 and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-H&amp;N35). Statistical analysis focused on changes in QoL domains. Results: In the analysis of SF-36 data, patients with radiation cystitis experienced an improvement in the pain domain (Mean difference [MD] = 58.4 ± 14.9, 95% CI). No other significant improvements were observed in the SF-36 data. In the EORTC QLQ-H&amp;N35 data, patients with head and neck radiation injury experienced an overall QoL improvement (MD = 12.9 ± 8.6, 95% CI) post-HBO2 treatment. Conclusions: HBO2 treatment demonstrated a benefit in reducing pain for patients with radiation cystitis and improving overall QoL in those with head and neck radiation injuries. Despite limitations, including a small sample size and incomplete survey data, the findings suggest that HBO2 can be a valuable intervention for patients suffering from chronic effects of radiation therapy, particularly in head and neck injury cases.

Incidence and Management of Radiation Cystitis After Pelvic Radiotherapy for Prostate Cancer: Analysis From a National Database

Radiation therapy has widely been used for cancers in the pelvis. Radiation cystitis, one of the late complications, presents often as hemorrhagic cystitis, which is refractory to the conventional therapy and may threaten the patient's life. We used hyperbaric oxygen therapy on patients with radiation cystitis to test its potential benifit. Ten patients aged from 46 to 81 years with a mean of 62 years underwent one or more courses of hyperbaric oxygen therapy according to their symptoms, consisting of 20 sessions (3 to 5 sessions a week) at the Department of Hyperbaric Medicine, the University of the Ryukyus Hospital in the 9-year period from 1985 to 1994. They included 8 patients having a history of cervical cancer, one with external genital cancer and one with vaginal cancer. During the 75 min hyperbaric oxygen therapy patients received 100% oxygen at 2 absolute atmosphere pressure in the Multiplace Hyperbaric Chamber. Hematuria subsided and subjective symptoms including urinary frequency improved in seven patients. Cystoscopic findings including mucosal edema, redness, and capillary dilation were partially improved. The procedure subjectively and objectively palliated the 10 patients in a favorable manner. To date we have not armed any active procedure to control radiation-induced refractory hemorrhagic cystitis in terms of efficacy, invasiveness, and adverse effects. Therefore, in consideration of our clinical results, hyperbaric oxygen therapy appears to be useful for radiation cystitis.