Emergent radiotherapy for pelvic malignancies: a narrative review.

BACKGROUND AND OBJECTIVE: Patients with primary genitourinary (GU), gynecologic (GYN) and gastrointestinal (GI) cancers can develop life-threatening or critical function-threatening symptoms that necessitate emergent intervention with palliative radiotherapy (RT). Unfortunately, research describing the use of RT in this critical setting is lacking. We aimed to review literature describing emergent palliative RT for primary pelvic malignancies and provide a narrative synthesis of relevant studies. METHODS: A medical librarian searched Ovid MEDLINE, Embase Classic, and Embase databases for relevant English language references from 1946-2022. No restrictions were placed on study type, publication type or date. References for GU, GYN and GI cancers were grouped and synthesized separately. KEY CONTENT AND FINDINGS: The treatment of bleeding from primary pelvic tumors was the only indication for emergent RT identified, however, no references reported dedicated cohorts of patients treated for bleeding in the emergent setting. Most references were retrospective single institution studies describing various dose fractionation schemes for non-emergent palliative RT. Outcome measures and response assessment times varied. The latency to hemostasis after RT commencement was not well described; most studies reported outcomes captured weeks or months following treatment. In general, high rates of hemostasis for GU, GYN and GI tumors have been reported following RT schedules ranging from a single fraction to many weeks of fractionated treatments. Bleeding seems to respond more favorably than other symptoms including pain and obstruction. CONCLUSIONS: Managing bleeding was the only indication for emergent RT identified in our search. Scant data exist that describe the latency to a hemostatic response following RT. This is an important knowledge gap in the literature given how commonly patients are affected by this complication of primary pelvic malignancies.

Uterine transposition versus uterine ventrofixation before radiotherapy as a fertility sparing option in young women with pelvic malignancies: Systematic review of the literature and dose simulation.

BACKGROUND: (Chemo)radiation may be a required treatment in young women with pelvic malignancies. Irradiation may result in ovarian and uterine failure, compromising the fertility of those patients. While ovarian transposition is an established method to move the ovaries away from the irradiation field, similar surgical procedures regarding the uterus remain investigational. The aim of this study was to carry out a systematic review of the literature on uterine displacement techniques (ventrofixation/transposition) and to simulate the radiation dose received by the uterus in different heights place after the procedures. METHODS: The systematic review was performed according PRISMA guidelines. PubMed, Scopus, Web of Science and EMBASE were queried to identify included study until March 2023. Retrospectively, a dosimetric study was also performed and Volumetric Modulated Arc Therapy (VMAT) radiotherapy treatment plans were calculated, to assess the dose received by the uterus according to hypothetical different displacement positions taking the case of irradiation for rectal or anal cancer as model. RESULTS: A total of 187 studies were included, after the screening 9 studies were selected for synthesis. Data from the dose simulation revealed that the transposition approach was the most protective with a maximum dose of about 3 and 8 Gy for anal and rectal cancer respectively. None of the simulated ventrofixation positions received a Dmean surpassing 14 Gy. CONCLUSION: According to the literature review and the simulation results of the present study we may conclude are feasible and safe as fertility sparing approach in young rectal/anal cancer patients.

[Management of radiation-induced intestinal injury:from multi-disciplinary team team to holistic integrative management].

Radiation-induced intestinal injury is a radiation injury of the colon and rectum after radiotherapy for pelvic malignant tumors. This condition affects multiple organs in the pelvis, making treatment challenging. In clinical practice, the most effective protocol is often determined through discussion by a multi-disciplinary team (MDT). However, due to the severity and complexity of radiation enteritis, many patients still experience poor diagnosis and treatment outcomes. Holistic integrative management (HIM) is a rapidly developing concept that has greatly enhanced clinical medicine in recent years. It improves the level of diagnosis, treatment, prevention, and rehabilitation from multiple dimensions of prevention, screening, diagnosis, treatment, and rehabilitation. In the context of radiation-induced intestinal injury, HIM also calls for the implementation of an individualized management system that focuses on the patient as a whole within the healthcare team. From the perspective of HIM, this article introduces some of the latest progress of radiation-induced intestinal injury in recent years.

Deep learning-based classification of organs at risk and delineation guideline in pelvic cancer radiation therapy.

Deep learning (DL) models for radiation therapy (RT) image segmentation require accurately annotated training data. Multiple organ delineation guidelines exist; however, information on the used guideline is not provided with the delineation. Extraction of training data with coherent guidelines can therefore be challenging. We present a supervised classification method for pelvis structure delineations where bowel cavity, femoral heads, bladder, and rectum data, with two guidelines, were classified. The impact on DL-based segmentation quality using mixed guideline training data was also demonstrated. Bowel cavity was manually delineated on CT images for anal cancer patients (n = 170) according to guidelines Devisetty and RTOG. The DL segmentation quality from using training data with coherent or mixed guidelines was investigated. A supervised 3D squeeze-and-excite SENet-154 model was trained to classify two bowel cavity delineation guidelines. In addition, a pelvis CT dataset with manual delineations from prostate cancer patients (n = 1854) was used where data with an alternative guideline for femoral heads, rectum, and bladder were generated using commercial software. The model was evaluated on internal (n = 200) and external test data (n = 99). By using mixed, compared to coherent, delineation guideline training data mean DICE score decreased 3% units, mean Hausdorff distance (95%) increased 5 mm and mean surface distance (MSD) increased 1 mm. The classification of bowel cavity test data achieved 99.8% unweighted classification accuracy, 99.9% macro average precision, 97.2% macro average recall, and 98.5% macro average F1. Corresponding metrics for the pelvis internal test data were all 99% or above and for the external pelvis test data they were 96.3%, 96.6%, 93.3%, and 94.6%. Impaired segmentation performance was observed for training data with mixed guidelines. The DL delineation classification models achieved excellent results on internal and external test data. This can facilitate automated guideline-specific data extraction while avoiding the need for consistent and correct structure labels.

The effect of nutritional interventions in acute radiation-induced diarrhoea in patients with primary pelvic cancer: A systematic review.

Acute radiation-induced diarrhoea (RID) is a well-known side effect of external radiation therapy for pelvic cancer. Acute RID is an unresolved clinical problem in approximately 80% of patients. We investigated the effect of nutritional interventions on acute RID in patients with pelvic cancer treated with curative radiotherapy. A search was conducted using PubMed, Embase.com, CINAHL, and Cochrane Library, from 1 January 2005 until 10 October 2022. We included randomised controlled trials or prospective observational studies. Eleven of the 21 identified studies had low quality of evidence, mainly because of low patient numbers distributed among several cancer diagnoses, and non-systematic assessment of acute RID. Interventions included probiotics (n = 6), prebiotics (n = 6), glutamine (n = 4), and others (n = 5). Five studies, of which two provided high quality evidence, showed that probiotics improved acute RID. Future well-designed studies investigating the effects of probiotics on acute RID are warranted. PROSPERO ID: CRD42020209499).

Laparoscopic ovarian transposition prior to pelvic radiation in young women with anorectal malignancies: a systematic review and meta-analysis of prevalence.

AIM: Young women undergoing radiotherapy (RT) for pelvic malignancies are at risk of developing premature ovarian insufficiency. Ovarian transposition (OT) aims to preserve ovarian function in these patients. However, its role in anorectal malignancy has yet to be firmly established. The aim of this review was to determine the effectiveness of laparoscopic OT in preserving ovarian function in premenopausal women undergoing neoadjuvant pelvic RT for anorectal malignancies. METHODS: MEDLINE, Embase and CENTRAL were systematically searched from inception through to May 2022. Articles were included if they evaluated ovarian function after OT in women with anorectal malignancies undergoing pelvic RT. The primary outcome was ovarian function preservation. The secondary outcome was 30-day postoperative morbidity following OT. RESULTS: From 207 citations, 10 studies with 133 patients with rectal or anal cancer who underwent OT prior to RT were included. Meta-analysis of pooled proportions of preserved ovarian function demonstrated an incidence of 66.9% (95% CI 55.0-79.0%, I2 = 43%). The 30-day postoperative morbidity rate was 1.2% (n = 1). There was heterogeneity in interventions and outcome reporting. CONCLUSIONS: Laparoscopic OT in premenopausal patients undergoing pelvic radiation for anorectal malignancies might be an effective technique at reducing ovarian exposure to RT. The meta-analyses must be interpreted within the context of clinical heterogeneity of the included studies. Further studies are required to fully investigate the outcomes of OT in patients undergoing pelvic radiation for anorectal malignancies.

Advances in the management of radiation-induced cystitis in patients with pelvic malignancies.

OBJECTIVE: Radiotherapy plays a vital role as a treatment for malignant pelvic tumors, in which the bladder represents a significant organ at risk involved during tumor radiotherapy. Exposing the bladder wall to high doses of ionizing radiation is unavoidable and will lead to radiation cystitis (RC) because of its central position in the pelvic cavity. Radiation cystitis will result in several complications (e.g. frequent micturition, urgent urination, and nocturia) that can significantly reduce the patient's quality of life and in very severe cases become life-threatening. METHODS: Existing studies on the pathophysiology, prevention, and management of radiation-induced cystitis from January 1990 to December 2021 were reviewed. PubMed was used as the main search engine. Besides the reviewed studies, citations to those studies were also included. RESULTS AND DISCUSSIONS: In this review, the symptoms of radiation cystitis and the mainstream grading scales employed in clinical situations are presented. Next, preclinical and clinical research on preventing and treating radiation cystitis are summarized, and an overview of currently available prevention and treatment strategies as guidelines for clinicians is provided. Treatment options involve symptomatic treatment, vascular interventional therapy, surgery, hyperbaric oxygen therapy (HBOT), bladder irrigation, and electrocoagulation. Prevention includes filling up the bladder to remove it from the radiation field and delivering radiation based on helical tomotherapy and CT-guided 3D intracavitary brachytherapy techniques.

Inguinal nodal clinical target volume delineation based on analysis of anatomical locations of normal and metastatic lymph nodes in pelvic malignant tumors.

PURPOSE: To optimize inguinal nodal clinical target volume (CTV) delineation based on analysis of the anatomical locations and embryonic development of normal and metastatic inguinal lymph nodes (ILNs) in patients with pelvic malignant tumors, including cervical, vaginal, vulvar, and anal tumors. MATERIALS AND METHODS: One hundred and eighty-one patients with pelvic malignancies and 415 involved ILNs treated with intensity-modulated radiation therapy were selected. First, the inguinal nodal CTV was divided into three fields as follows: I, horizontal superficial inguinal field; II, vertical superficial inguinal field; and III, deep inguinal field. Initial CTV delineation of each field was based on analysis of the anatomical locations and embryonic development of normal ILNs. Subsequently, the positions of metastatic ILNs relative to the proper anatomical landmarks or vessels were determined to optimally delineate the final ILN CTV contours. Eighty percent of the data acquired (n = 145) were used as test data for optimization and analysis, the remaining 20% (n = 36) were used for delineation validation. RESULTS: In total, 252 positive ILNs in 103 cervical cancer patients, 94 positive ILNs in 41 vulvar cancer patients, 8 positive ILNs in 3 vaginal cancer patients, and 61 positive ILNs in 34 anal cancer patients were enrolled. Detailed target volume contouring guidelines for the three divisions were determined on images. All positive ILNs from the remaining 20% patients were located in the CTV boundaries delineated based on analysis of 80% of the data acquired. Importantly, the final inguinal nodal CTV field determined using our method was substantially smaller than defined by existing atlases, and the femoral vessels were excluded in the delineation. CONCLUSIONS: This study provided anatomical, embryonic, surgical, and statistical evidence to facilitate ILN CTV delineation in radiotherapy planning for patients with pelvic malignancies.

Dose estimation for cone-beam computed tomography in image-guided radiation therapy for pelvic cancer using adult mesh-type reference computational phantoms.

The use of cone-beam computed tomography (CBCT) is expanding owing to its installation in linear accelerators for radiation therapy, and the imaging dose induced by this system has become the center of attention. Here, the dose to patients caused by the CBCT imager was investigated. Organ doses and effective doses for male and female mesh-type reference computational phantoms (MRCPs) and pelvis CBCT mode, routinely used for pelvic irradiation, were estimated using the Particle and Heavy Ion Transport Code System. The simulation results were confirmed based on the point-dose measurements. The estimated organ doses for male MRCPs with/without raised arms and for female MRCPs with/without raised arms were 0.00286-35.6 mGy, 0.00286-35.1 mGy, 0.00933-39.5 mGy, and 0.00931-39.0 mGy, respectively. The anticipated effective doses for male MRCPs with/without raised arms and female MRCPs with/without raised arms irradiated by pelvis CBCT mode were 4.25 mSv, 4.16 mSv, 7.66 mSv, and 7.48 mSv, respectively. The results of this study will be useful for patients who undergo image-guided radiotherapy with CBCT. However, because this study only covered one type of cancer with one type of imager, and image quality was not considered, more studies should be conducted to estimate the radiation dose from imaging devices in radiation therapy.

Complications and Functional Outcome Differences in Carbon Ion Radiotherapy and Surgery for Malignant Bone Tumors of the Pelvis: A Multicenter, Cohort Study.

BACKGROUND: Carbon ion radiotherapy (CIRT) is an evolving treatment option for malignant pelvic tumors in patients with poor surgical indications. However, the difference in complications and functional outcomes between CIRT and surgery is poorly understood. This study compares the complications and functional outcomes of CIRT and surgery to facilitate treatment selection. METHODS: A total of 28 patients who underwent CIRT for pelvic bone tumors while theoretically meeting the surgical resection criteria were included. Sixty-nine patients who underwent surgery for pelvic bone tumors were included as controls. Major complication rates and functional outcomes (ambulatory, pain, urination, constipation) were evaluated and compared at several time points (pretreatment, discharge, and final follow-up) between the groups. RESULTS: Early (within 90 days) major complications were not observed in the CIRT group but occurred in 30% of the surgery group, which was statistically significant (P < 0.001). In contrast, late (after 90 days) major complications occurred more often in the CIRT group than in the surgery group (18% and 4%, respectively; P = 0.042). From pretreatment until discharge, all functional outcomes in the surgery group deteriorated (P < 0.001 for all) but did not change in the CIRT group (P = 0.77-1.00). At the final follow-up, all functional outcomes showed no significant intergroup difference (P = 0.28-0.92) due to the recovery trend in the surgery group and the deterioration trend in the CIRT group. CONCLUSIONS: Compared with surgery, CIRT may have favorable safety and stable functional outcomes in the short-term but more late complications. Mid-term functional outcomes were similar between the groups.

Clinical efficacy and safety analysis of CT-guided 125I implantation in the treatment of recurrent or metastatic pelvic malignant tumor.

PURPOSE: This study was conducted to evaluate the clinical efficacy and safety of computed tomography (CT)-guided 125I implantation in the treatment of recurrent or metastatic pelvic malignant tumor. METHODS AND MATERIALS: This retrospective study analyzed the data of 30 patients with recurrent and metastatic pelvic malignant tumor who were treated with CT-guided 125I implantation between January 2016 and December 2020. Disease control rate, objective remission rate, overall survival (OS), pain relief rate, quality of life score, and complications were evaluated after the followup. RESULTS: Median followup was 20.1 (7-30) months. Disease control rate was 86.67% at 6 months. Objective response rates at 1, 3, and 6 months were 36.67%, 60%, and 56.67%, respectively. OS rates at 12 and 24 months were 76.67% (23/30) and 33.33% (10/30), respectively. Progression-free survival rates at 12 and 24 months were 63.33% (19/30) and 33.33% (10/30), respectively. Postoperative pain relief rate was 86.67% (26/30). There were no major bleeding, pelvic abscess, intestinal fistula, intestinal perforation, and other serious complications. CONCLUSIONS: CT-guided 125I seed implantation in the treatment of patients with pelvic malignant tumor is a simple operation and less traumatic and can improve patients' quality of life and reduce tumor load.

Safety and Efficacy of Palliative Radiotherapy (25 Gy × 5 Fractions) for Symptomatic Pelvic Tumors.

BACKGROUND/AIM: Palliative radiotherapy is one of the effective treatments for pelvic tumors with bleeding or pain. In this study, we evaluated the safety and efficacy of palliative radiotherapy (RT) for symptomatic pelvic tumors when delivered as 25 Gy in 5 fractions. PATIENTS AND METHODS: We retrospectively analyzed 34 patients (gynecological cancer: n=14, rectal cancer: n=5, metastatic pelvic bone tumor: n=7, metastatic pelvic lymph node tumor: n=5, synovial sarcoma of the pelvis: n=1, prostate cancer: n=1, and urothelial cancer: n=1), who were treated between July 2016 and July 2021. The symptoms were bleeding in 16 patients, pain in 17 patients, and both bleeding and pain in 1 patient. The hemostatic effect of RT was evaluated with pre- and post-treatment hemoglobin (Hb) values. If the Hb levels reached a nadir and increased thereafter, we considered that there is a hemostatic response. The pain was evaluated with a numerical rating scale (NRS) and treatment response was defined as a decrease in NRS. RESULTS: Their median follow-up period was 4 months. A hemostatic response was observed in 82% of patients (14 of 17 patients). A pain relief response was observed in 78% of patients (14 of 18 patients). Acute adverse effects (AEs) included grade 1 diarrhea (n=3), grade 1 dermatitis (n=1) and grade 1 urinary frequency (n=1); late AEs have not been observed so far. CONCLUSION: 25 Gy of palliative RT in 5 fractions seems to be safe and effective for symptomatic pelvic tumors, similar to conventional palliative RT schedules.

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

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.

Construction of a predictive model for radiation proctitis after radiotherapy for female pelvic tumors based on machine learning. / åŸºäºŽæœºå™¨å­¦ä¹ æž„å»ºå¥³æ€§ç›†è ”è‚¿ç˜¤æ”¾å°„æ²»ç–—åŽæ”¾å°„æ€§ç›´è‚ ç‚Žçš„é¢„æµ‹æ¨¡åž‹.

OBJECTIVES: Radiation therapy is a main method for female pelvic malignancies, which can cause some adverse reactions, such as radiation proctitis (RP). The incidence of RP is highly positively correlated with radiation dose. There is an urgent need for a scientific method to accurately predict the occurrence of RP to help doctors make clinical decisions. In this study, based on the clinical data of female pelvic tumor patients and dosimetric parameters of radiotherapy, the random forest method was used to screen the hub features related to the occurrence of RP, and then a machine learning algorithm was used to construct a risk prediction model for the occurrence of RP, in order to provide technical support and theoretical basis for the prediction and prevention of RP. METHODS: A total of 100 female patients with pelvic tumors, who received static three-dimensional conformal intensity-modulated radiation therapy in the Department of Radiation Oncology of the Affiliated Hospital of Xiangnan University from January 2019 to December 2020, were retrospectively collected, and their clinically relevant data and radiotherapy planning system data were collected. During radiotherapy and 18 months after radiotherapy, 35 cases developed RP (RP group), and the remaining 65 cases had no RP (non-RP group). The clinical and dosimetric characteristics of patients were ranked by the importance of random forest algorithm, and the independent prognostic characteristics associated with the occurrence of RP were selected for machine learning modeling. A total of 6 machine learning algorithms including support vector machines, random forests, logistic regression, lightweight gradient boosting machines, Gaussian naïve Bayes, and adaptive enhancement were used to build models. The performance of the model was evaluated by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1 score. Finally, the random forest model was determined as the prediction model, and the calibration curve and decision curve of the prediction model were drawn to evaluate the accuracy and clinical benefit of the model. RESULTS: The parameters for random forest prediction model in the training set were as follow: AUC, 1.000, accuracy, 0.988, sensitivity, 1.000, specificity, 1.000, positive predictive value, 1.000, negative predictive value, 0.981, and F1 score, 1.000. In validation set, AUC was 0.713, accuracy was 0.640, sensitivity was 0.618, specificity was 0.822, positive predictive value was 0.500, negative predictive value was 0.656, and F1 score was 0.440. Random forest showed high predictive performance. Moreover, the Brief of the calibration curve for the prediction model was 0.178, the prediction accuracy was high, and the decision curve showed that the prediction model could benefit clinically. CONCLUSIONS: Based on the clinical and dosimetric parameters for the female pelvic tumor patients, the prediction model of radiation proctitis constructed by random forest algorithm has high predictive ability and strong clinical usability.

Sexual health and wellbeing among female pelvic cancer survivors following individualized interventions in a nurse-led clinic.

PURPOSE: Treatment-induced sexual and intestinal dysfunctions coexist among women after pelvic radiotherapy. We aimed to explore if sexual health and wellbeing may be improved after radiotherapy following nurse-led interventions and if an association exists between improved intestinal health and sexual health. METHODS: A population-based cohort of women treated with pelvic radiotherapy underwent interventions at a nurse-led clinic at Sahlgrenska University Hospital, Sweden, from 2011 to 2017. Self-reported questionnaires were used, pre- and post-intervention, to compare self-reported changes in sexual health and wellbeing. A regression model was performed to explore the association between intestinal and wellbeing variables. RESULTS: Among the 260 female pelvic cancer survivors included in the study, more women reported increased than decreased satisfaction with overall sexual health post-intervention (26.0% vs. 15.3%, p = 0.035). They also reported significantly reduced superficial genital pain (25.8% vs. 13.1%, p ≤ 0.025), reduced deep genital pain (23.1% vs. 8.0%, p ≤ 0.001), increased QoL (42.7% vs. 22.4%, p < 0.001), and reduced levels of depression (43.1% vs. 28.0%, p = 0.003) or anxiety (45.9% vs. 24.4%, p < 0.001) post-intervention. We found a significant association between reduced urgency to defecate and improved satisfaction with overall sexual health (RR 3.12, CI 1.27-7.68, p = 0.004) and between reduced urgency to defecate with fecal leakage and reduced anxious mode (RR 1.56, CI 1.04-2.33, p = 0.021). CONCLUSION: Sexual health and wellbeing can be improved by interventions provided in a nurse-led clinic focusing on physical treatment-induced late effects. Further research to optimize treatment strategies in female pelvic cancer survivors is needed.

Symptom burden and health-related quality of life six months after hyperbaric oxygen therapy in cancer survivors with pelvic radiation injuries.

PURPOSE: Late radiation tissue injuries (LRTIs) after treatment for pelvic cancer may impair health related quality of life (HRQoL). Hyperbaric oxygen therapy is an adjuvant therapy for LRTIs, but limited studied. The aim of this study was to explore the development and association between symptoms of LRTI and HRQoL following hyperbaric oxygen treatment. METHODS: A pretest-posttest design was used to evaluate the changes in pelvic LRTIs and HRQoL from baseline (T1), immediately after treatment (T2) and at six-month follow-up (T3). EPIC and EORTC-QLQ-C30 were used to assess LRTIs and HRQoL. Changes were analysed with t-tests, and associations with Pearson's correlation and multiple regression analyses. RESULTS: Ninety-five participants (mean age 65 years, 52.6% men) were included. Scores for urinary and bowel symptoms, overall HRQoL, all function scales and the symptoms scales sleep, diarrhoea, pain and fatigue were significantly improved six months after treatment (P-range = 0.00-0.04). Changes were present already at T2 and maintained or further improved to T3. Only a weak significant correlation between changes in symptoms and overall HRQoL was found (Pearson r-range 0.20-0.27). CONCLUSION: The results indicate improvement of pelvic LRTIs and HRQoL following hyperbaric oxygen therapy, corresponding to minimal or moderate important changes. Cancer survivors with pelvic LRTIs and impaired HRQoL may benefit from undergoing hyperbaric oxygen therapy. Especially the reduced symptom-severity and improved social- and role function can influence daily living positively. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03570229. Released 2. May 2018.

Therapeutics in radiation-induced proctopathy: a systematic review

Malignant neoplasms are increasingly prevalent in the daily clinical practice. Up to 61% of patients with pelvic malignancies undergo pelvic radiotherapy in different doses, which may cause intestinal damage, and the rectum is the segment most frequently affected due to its fixed position in the pelvis. Currently, there are several strategies to minimize the effects of radiation on the tissues surrounding the neoplastic site; despite those strategies, radiotherapy can still result in serious damage to organs and structures, and these injuries accompany patients throughout their lives. One of the most common damages resulting from pelvic radiotherapy is acute proctitis.The diagnosis is confirmed by visualizing the rectal mucosa through rigid or flexible rectosigmoidoscopy and colonoscopy. The objective of the present study was to review the forms of radiation-induced proctopathytherapy, and to evaluate the results of each method to propose a standardization for the treatment of this pathology. Despite the prevalence of radiation-induced proctopathy, there is no definitive standardized treatment strategy so far. The first approach can be tried with local agents, such as mesalazine and formalin. For refractory cases, control can usually be achieved with argon plasma coagulation, hyperbaric oxygen, and radiofrequency ablation therapies. Regarding the study of radiation-induced proctopathy, there is a lack of robust studies with large samples and standardized therapies to be compared. There is a lack of double-blinded, randomized controlled studies to determine a definitive standard treatment algorithm. (AU)

Randomised single centre double-blind placebo controlled phase II trial of Tocovid SupraBio in combination with pentoxifylline in patients suffering long-term gastrointestinal adverse effects of radiotherapy for pelvic cancer: The PPALM study.

BACKGROUND: Preclinical data suggest that combined gamma-tocotrienol with pentoxifylline ameliorates radiotherapy-induced gastrointestinal damage. AIM: To test whether gastrointestinal symptoms arising after radiotherapy, and persisting after maximal medical therapy, can be improved using Tocovid SupraBio 200 mg and pentoxifylline 400 mg orally twice daily for one year. Patients stratified by severity of symptoms, and randomised to active treatment or matched placebo were assessed after 12 months. The primary end point was improvement in gastrointestinal symptoms measured using the Inflammatory Bowel Disease Questionnaire, bowel subset score. Changes in bio-markers of fibrosis were assessed. RESULTS: 62 patients, median age 66, 34(55%) treated for prostate, 21(34%) gynaecological, 6(10%) anal and one(1%) rectal cancer were recruited; 40(65%) randomised to treatment, 22(35%) to placebo, 39 months (median) after radiotherapy completion. Gamma tocotrienol was not detected in serum in 41% of treated patients, despite good compliance with study medication. Treatment was completed in 28(70%) and 17(77%) patients in the treatment and placebo groups respectively. No improvement in symptom scores nor in quality of life was identified. Thirteen serious adverse events occurred. A transient ischaemic attack, was possibly related to pentoxifylline, others were assessed as unlikely to be related to treatment. Levels of EGF, PDGF and FGF were significantly reduced and consistent trends in reduced inflammation were seen during treatment but were not sustained once treatment ended. SUMMARY: This single centre study closed prematurely and therefore data interpretation is of necessity limited. No clinical benefit was demonstrated. However, biochemical data suggest that this intervention does have anti-inflammatory and anti-fibrotic effects.

Technical note: Evaluation of a silicone-based custom bolus for radiation therapy of a superficial pelvic tumor.

PURPOSE: Use of standard-of-care radiation therapy boluses may result in air-gaps between the target surface and bolus, as they may not adequately conform to each patient's unique topography. Such air-gaps can be particularly problematic in cases of superficial pelvic tumor radiation, as the density variation may result in the radiation delivered to the target site being inconsistent with the prescribed dose. To increase bolus fit and thereby dose predictability and homogeneity, we designed and produced a custom silicone bolus for evaluation against the clinical standard. METHODS: A custom bolus was created for the pelvic regions of both an anthropomorphic phantom and a pelvic patient with squamous cell carcinoma of the penile shaft. Molds were designed using computed tomography (CT) scans, then 3D-printed and cast with silicone rubber to yield the boluses. Air-gap measurements were performed on custom and standard-of-care Superflab gel sheet boluses by analyzing total volume between the bolus and target surface, as measured from CT scans. Therapeutic doses of radiation were delivered to both boluses. Radiation dose was measured and compared to the expected dose using nine optically stimulated luminescent dosimeters (OSLDs) placed on the phantom. RESULTS: Mean air-gap volume between the bolus and phantom was decreased from 314 ± 141 cm3 with the standard bolus to 4.56 ± 1.59 cm3 using the custom device. In the case of the on-treatment patient, air-gap volume was reduced from 169 cm3 with the standard bolus to 46.1 cm3 with the custom. Dosimetry testing revealed that the mean absolute difference between expected and received doses was 5.69%±4.56% (15.1% maximum) for the standard bolus and 1.91%±1.31% (3.51% maximum) for the custom device. Areas of greater dose difference corresponded to areas of larger air-gap. CONCLUSIONS: The custom bolus reduced air-gap and increased predictability of radiation dose delivered compared to the standard bolus. The custom bolus could increase the certainty of prescribed dose-delivery of radiation therapy for superficial tumors.

[Chronic radiation-induced rectal injury after adjuvant radiotherapy for pelvic malignant tumors: report based on a phase 3 randomized clinical trial].

Objective: Radiotherapy is one of the standard treatments for pelvic malignant tumors. However, researches associated with intestinal radiation injury and the quality of life (QoL) of patients receiving radiotherapy were lacking in the past. This study aims to analyze the occurrence of radiation-induced rectal injury after adjuvant radiotherapy for pelvic malignant tumors and call for more attention on this issne. Methods: A retrospectively observational study was conducted. Case data of cervical cancer patients from the database of STARS phase 3 randomized clinical trial (NCT00806117) in Sun Yat-sen University Cancer Center were analyzed. A total of 848 cervical cancer patients who received adjuvant radiation following hysterectomy and pelvic lymphadenectomy in Sun Yat-sen University Cancer Center from February 2008 to August 2015 were recruited. The pelvic radiation dosage was 1.8 Gy/day or 2.0 Gy/day, five times every week, and the total dosage was 40-50 Gy. Among 848 patients, 563 patients received radiation six weeks after surgery, of whom 282 received adjuvant radiation alone and 281 received concurrent chemoradiotherapy (weekly cisplatin); other 285 patients received sequential chemoradiotherapy (paclitaxel and cisplatin). Acute adverse events, chronic radiation damage of rectum, and QoL were collected and analyed. The digestive tract symptoms and QoL were evaluated based on EORTC QLQ-C30 questionnaires at one week after surgery (M0), during adjuvant therapy period (M1), and at 12 months and 24 months after the completion of treatments (M12 and M24), respectively. Higher scores in the functional catalog and overall quality of life indicated better quality of life, while higher scores in the symptom catalog indicated severe symptoms and worse QoL. Chronic radiation rectal injury was defined as digestive symptoms that were not improved within three months after radiotherapy. Grading standard of acute adverse events and chronic radiation rectal injury was according to the gastrointestinal part of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI-CTCAE Version 4.0). Results: The mean total radiation dosage of 848 patients was (47.8±4.6) Gy. During adjuvant therapy, the common symptoms of acute intestinal dysfunction were nausea (46.0%, 390/848), vomiting (33.8%, 287/848), constipation (16.3%, 138/848) and abdominal pain (10.3%, 87/848). At M12 and M24, the number of 0 QLQ-C30 questionnaires collected was 346 and 250, respectively. QLQ-C30 questionnaires showed that the scores of nausea or vomiting, appetite decrease, diarrhea, constipation, etc. were improved obviously at M12 or M24 compared with those at M0 or during M1 (all P<0.05). As the extension of the follow-up time, the score of the overall QoL of patients gradually increased [M0: 59.7 (0.0-100.0); M1: 63.1 (0.0-100.0); M12: 75.2 (0.0-100.0); M24: 94.1 (20.0-120.0); H=253.800, P<0.001]. Twelve months after the completion of treatments, the incidence of chronic radiation rectal injury was 9.8% (34/346), mainly presenting as abdominal pain, constipation, stool blood, diarrhea, mostly at level 1 to 2 toxicity (33/34, 97.1%). One patient (0.3%) developed frequent diarrhea (>8 times/d), which was level 3 toxicity. Twenty-four months after all treatments, the incidence of chronic radiation rectal injury was 9.6% (24/250), which was not decreased significantly compared to that in the previous period (χ(2)=0.008, P=0.927). The symotoms of one patient with level 3 toxicity was not relieved. Conclusions: The common symptoms of patients with pelvic maligant tumors during postoperative adjuvant radiotherapy include nausea, vomiting, constipation, abdominal pain and diarrhea. These symptoms are alleviated obviously at 12 and 24 months after adjuvant radiotherapy, and the QoL is significantly improved. However, a few patients may develop chronic radiation rectal injury which is not improved for years or even decades, and deserves attention in clinical practice.