Current challenges in the assessment and management of radiotherapy-induced vaginal stenosis.

There are more than 13,000 new cases of cervical cancer each year in the United States and approximately 245,000 survivors. External beam radiation and brachytherapy are the front-line treatment modalities, and 60% of patients develop vaginal damage and constriction, i.e., stenosis of the vaginal vault, greatly impeding sexual function. The incidence of vaginal stenosis (VS) following radiotherapy (RT) for anorectal cancer is 80%. VS causes serious quality of life (QoL) and psychological issues, and while standard treatment using self-administered plastic dilators is effective, acceptance and compliance are often insufficient. Based on published patient preferences, we have pursued the design of a soft inflatable dilator for treating radiotherapy-induced vaginal stenosis (VS). The critical component of the novel device is the dilator balloon wall material, which must be compliant yet able to exert therapeutic lateral force levels. We selected a commercially available silicone elastomer and characterized its stress–strain characteristics and hyperelastic properties. These parameters were quantified using uniaxial tensile testing and digital image correlation (DIC). Dilator inflation versus internal pressure was modeled and experimentally validated in order to characterize design parameters, particularly the dilator wall thickness. Our data suggest that an inflatable silicone elastomer-based vaginal dilator warrants further development in the context of a commercially available, well-tolerated, and effective device for the graded, controlled clinical management of radiotherapy-induced VS.

The aim of our study was to determine the incidence, timing, and severity of vaginal stenosis in patients with carcinoma of the cervix who had received pelvic and/or vaginal radiotherapy as part of their treatment. We also sought to determine if there were any predisposing factors for the development of stenosis. A retrospective chart review was undertaken for all the patients diagnosed with carcinoma of the cervix between January 1, 1990, and December 31, 2000 and treated with pelvic and/or vaginal radiation at Westmead Hospital. Since January 1, 1990, data regarding vaginal stenosis has been prospectively recorded on all the patients. Data collected included patient demographics, stage of disease, treatments administered, and incidence, timing, and severity of vaginal stenosis. One hundred and eighty-eight patients were treated. Mean age was 58.6 years. Thirteen percent of patients had stage IB disease, 45% had stage II disease, 39.5% had stage III disease, and 1.5% had stage IV disease. One hundred and seventy-nine patients returned for follow-up, and data regarding vaginal toxicity were available in 98%. Twenty-seven percent had grade 1 toxicity (partial stenosis or shortening but not complete occlusion), and 11% had grade 2 (complete occlusion). Stenosis of any grade was noted at a mean of 9.6 months and median of 7.5 months (range, 26 days–5.6 years) from completion of treatment. The only prognostic factor associated with increased risk of stenosis was age greater than 50 years (odds ratio 2.26). Vaginal stenosis is a common complication of pelvic and vaginal radiotherapy, occurring in 38% of patients. Stenosis occurs most often in the first year after treatment. Patients over the age of 50 are most at risk.

PurposeTo compare the survival and toxicity outcomes in patients with endometrial cancer treated with either high-dose-rate (HDR) or low-dose-rate (LDR) vaginal brachytherapy (VBT) following external beam radiotherapy (EBRT).Material and methodsFrom January 2000 to December 2014, patients with endometrial cancer after radical hysterectomy with/without pelvic and/or para-aortic lymphadenectomy were treated with adjuvant EBRT (45 Gy, 1.8 Gy/day to the whole pelvis) and subsequent VBT boost (HDR dose of 7 Gy in one fraction or LDR VBT dose of 25 Gy). The dose was prescribed at 0.5 cm from the surface of the applicator and the proximal half to two-thirds of the vagina was irradiated. The outcomes of patients were evaluated in terms of local control (LC), overall survival (OS), and rates of adverse events.ResultsWe analyzed data of 200 patients treated with EBRT followed by HDR VBT boost in 78 patients and LDR VBT boost in 122 patients. With a median follow-up of 25 months (range, 6-163), 5-year OS was 98% and 97% in the LDR and HDR groups, respectively (p = 0.37). The 5-year LC was similar (93% in both groups) (p = 0.81). In multivariate analyses, none of the factors assessed (age, stage, grade) impacted OS (p = 0.37) or LC (p = 0.81). Patients treated with LDR VBT after EBRT had higher rates of acute gastrointestinal toxicity. No differences were found in acute genitourinary or hematological toxicities. Late toxicity such as vaginal stenosis was registered during regular follow-up visits and was similar in the two groups (p = 0.67).ConclusionsIn our analysis, there were no differences in terms of OS and late toxicity outcomes for patients receiving LDR or HDR VBT. HDR VBT is a safe technique in comparison to LDR VBT.

Background: We sought to determine the outcomes of adjuvant small pelvic external beam radiotherapy (EBRT) and prognostic factors for survival and disease control. Patients and Methods: We retrospectively evaluated 113 cervical cancer patients treated with postoperative median 50.4-Gy small pelvic EBRT. We treated the surgical bed, bilateral parametria, paravaginal soft tissues, upper third of the vagina, and presacral lymphatics. Results: Median follow-up of all patients and survivors was 58 and 67 months, respectively. The 2- and 5-year overall survival (OS) and disease-free survival rates were 91 and 82%, and 85 and 74%, respectively. The locoregional failure rate was 10%. Age was a significant predictor for OS and distant metastasis-free survival (DMFS) on univariate analysis. The number of dissected lymph nodes being < 30 negatively affected the pelvic recurrence-free survival. The only independent predictor on multivariate analysis was older age for DMFS. Although no severe acute toxicity was observed, late grade ≥ 3 toxicity developed in 8 patients. Conclusion: Small pelvic EBRT produces satisfactory survival and locoregional control with acceptable toxicity, and can be an alternative to whole pelvic EBRT in selected cervical cancer patients.

Primary vaginal cancer treated with high-dose rate brachytherapy and intraprocedural magnetic resonance imaging.

Fibroblast to myofibroblast differentiation is a key feature of wound-healing in soft tissues, including the vagina. Vaginal fibroblasts maintain the integrity of the vaginal wall tissues, essential to keep pelvic organs in place and avoid pelvic organ prolapse (POP). The micro-environment of vaginal tissues in POP patients is stiffer and has different extracellular matrix (ECM) composition than healthy vaginal tissues. In this study, we employed a series of matrices with known stiffnesses, as well as vaginal ECMs, in combination with vaginal fibroblasts from POP and healthy tissues to investigate how matrix stiffness and composition regulate myofibroblast differentiation in vaginal fibroblasts. Stiffness was positively correlated to production of α-smooth muscle actin (α-SMA). Vaginal ECMs induced myofibroblast differentiation as both α-SMA and collagen gene expressions were increased. This differentiation was more pronounced in cells seeded on POP-ECMs that were stiffer than those derived from healthy tissues and had higher collagen and elastin protein content. We showed that stiffness and ECM content regulate vaginal myofibroblast differentiation. We provide preliminary evidence that vaginal fibroblasts might recognize POP-ECMs as scar tissues that need to be remodeled. This is fundamentally important for tissue repair, and provides a rational basis for POP disease modelling and therapeutic innovations in vaginal reconstruction.

Comorbidity and Primary Treatment for Localized Prostate Cancer: Data From C <scp>a</scp> PSURE™

Control of PET-Positive Lymph Nodes Treated with Definitive Chemoradiation in Locally Advanced Cervical Cancer

Brachytherapy (BT) plays a fundamental role in the treatment of gynecological cancers. Patient education for vaginal self-management and dilator use post-BT involves an interdisciplinary team of healthcare professionals (HCPs) and there is a paucity of post-BT education guidelines. Our objective was to determine the educational needs of gynecological cancer patients surrounding vaginal self-management post-BT and to determine enablers and barriers to the provision of education by HCPs. This cross-sectional study recruited gynecological oncology patients receiving external beam radiotherapy and BT for curative intent. Patients completed a questionnaire to assess their vaginal self-management educational needs, preferred education modality, and desired timing of post-BT education. HCPs were invited to complete a questionnaire to identify enablers and barriers to providing BT education. Twenty patients and 53 HCPs participated. All patients rated each topic as very important/important with information about preventing vaginal stenosis as the most important overall (89%). When asked about topics they addressed during BT education, most HCPs reported that "explaining what vaginal stenosis is and the negative effects of stenosis" was always discussed with patients (N = 37/49, 77%). Barriers to providing post-BT education, including the patients' language and culture, as well as enablers, such as the use of written resources and tools for patients, were identified. Despite a high level of engagement, current education surrounding vaginal self-management post-BT may be inadequate.

Postoperative vaginal cuff irradiation using high dose rate remote afterloading: A Phase II clinical protocol

Vaginal stenosis and hydrometrocolpos: late complication of inadvertent perivaginal placement of an artificial urinary sphincter in prepubertal girls

To assess local control, survival and complications in patients with cervical carcinoma Stage IIB treated radically with transperineal Iridium-192 low-dose rate interstitial brachytherapy following external beam radiotherapy. 65 women (age 25-70 years, mean 47 years) with cervical carcinoma Stage IIB were initially treated with external beam radiotherapy on a telecobalt or 6 MV linear accelerator to a dose of 50 Gy delivered in 5-6 weeks. After 2-3 weeks of completing external radiation, patients received interstitial brachytherapy with Iridium-192 (activity 0.5-1 mCi/cm) using a Syed-Neblett perineal template. The median dose delivered to the implant volume was 24 Gy (range 20-32 Gy) delivered at an average dose rate of 0.70 Gy/h (range 0.40-1.20 Gy/h). A point defined at 1.5 cm lateral to the central uterine tandem at the level of os was taken as a representative for assessing the dose to the cervix. Mean doses delivered by interstitial brachytherapy to point A, cervix, point B and rectum were 38 Gy, 34 Gy, 16 Gy and 16 Gy, respectively. At a median follow-up of 53 months, the actuarial disease free survival and overall survival for 65 patients at both 5 and 10 years was 64% and 44%, respectively. Response to radiotherapy was a strong predictor of local control with 82% of patients continuing to have pelvic control after initial complete response. Overall, nine (14%) patients had persistent disease, ten (15%) developed a central recurrence after initial control and three patients developed distant metastasis on follow-up. No patient had any immediate treatment-related complication. Late toxicity included grade I-II rectal reactions in five patients and grade IV bladder complication (vesico-vaginal fistula) in two patients. 5 years after treatment, one patient developed intestinal obstruction, which was relieved after conservative management. Two patients developed vaginal stenosis. The 5- and 10-year disease free survival was 48% in patients aged less than 45 years as compared to 80% in patients of more than 45 years (p = 0.009). Dose to the cervical point was a prognostic indicator with 5- and 10-year disease free survival of 47% in patients who received < 35 Gy in comparison to 80% in patients who had > 35 Gy (p = 0.03). There was no difference in local control and survival in patients with minimal and moderate parametrial involvement. Bulky disease (> 4 cm) at presentation and a longer gap between external radiation and brachytherapy showed a trend towards inferior local control. Interstitial brachytherapy after external beam irradiation in patients with cervical carcinoma Stage IIB results in acceptable local control, survival and complication rates. Increased dose to the cervical disease results in improved local control and survival and should therefore be considered while optimizing brachytherapy treatment plans. Comparison of the results with those of standard intracavitary therapy remains to be proven in a randomized trial.

Background: The COVID-19 pandemic has led both to an increased need for and a shortage of trained healthcare staff globally. The population of undergraduate students in health and social care is diverse and widening participation practices are vital to support these students to navigate through academic study. In post-pandemic higher education environments, where hybrid and blended approaches to learning are now more commonplace, research relating to students’ experience, use, perception and understanding of assessment criteria and feedback is ever more important. Aim: The present review and qualitative thematic meta-synthesis is a secondary analysis following a primary study that aimed to understand students’ understanding of the relationship between assessment criteria and assessment feedback. Methods: Using an integrative systematic review method, 1754 articles were initially identified via electronic searches. Study selection was conducted in a series of stages and by agreement between reviewers; 35 articles were selected that met the relevancy criteria. A screening process excluded quantitative and mixed-methods studies, leaving nine qualitative studies for analysis. Results: Findings highlighted two intersecting themes relating to the importance of “Scaffolding assessment and feedback” and how this linked to students’ “Engagement and perceived self-efficacy”. A constructivist educational framework is proposed to scaffold students’ engagement and perceived self-efficacy in relation to assessment criteria and assessment feedback. Elements in this framework include: (1) multiple modalities for feedback to support inclusive best practice; (2) the provision of mentorship and / or reflective spaces for processing assessment criteria and feedback; and (3) a goal-oriented approach to students’ engagement with assessment criteria and feedback. Conclusion: Such a framework will make assessment and feedback more transparent and accessible for students, broaden their focus beyond grade attainment, enable them to make links between assessment criteria, assignment writing and assessment feedback, and support inclusivity and staff-student relationships in the context of post-pandemic educational systems.

Cancer de la prostate 2010. Innovations thérapeutiques

Background: The causal link between elevated systemic inflammation biomarkers and poor survival has been demonstrated in cancer patients. However, the evidence for this correlation in endometrial cancer (EC) is too weak to influence current criteria of risk assessment. Here, we examined the role of inflammatory indicators as a tool to identify EC patients at higher risk of death in a retrospective observational study. Methods: A total of 155 patients surgically diagnosed with EC stage I-III FIGO 2009 and treated with postoperative External Beam Radiotherapy (EBRT) ± brachytherapy and chemotherapy according to ESMO-ESTRO-ESGO recommendation for patients at high risk of recurrence at the Gustave Roussy Institut, France, and Hospital Clínic, Spain, between 2008 and 2017 were evaluated. The impact of pre-treatment Neutrophil-to-Lymphocyte Ratio (NLR ≥ 2.2), Monocyte-to-Lymphocyte Ratio (MLR ≥ 0.18), Systemic Immune-Inflammatory Index (SII ≥ 1100) and lymphopenia (<1.0×109/L) on overall survival (OS), cancer-specific survival and progression-free survival was evaluated. Subsequently, a cohort of 142 patients within high-advanced risk groups according to ESMO-ESGO-ESTRO classification was evaluated. Results: On univariate analysis, NLR (HR = 2.2, IC 95% 1.1–4.7), SII (HR = 2.2, IC 95% 1.1–4.6), MLR (HR = 5.0, IC 95% 1.1–20.8) and lymphopenia (HR = 3.8, IC 95% 1.6–9.0) were associated with decreased OS. On multivariate analysis, NLR, MLR, SII and lymphopenia proved to be independent unfavorable prognostic factors. Conclusions: lymphopenia and lymphocytes-related ratio are associated with poorer outcome in surgically staged I-III FIGO EC patients classified as high risk and treated with adjuvant EBRT and could be considered at cancer diagnosis. External validation in an independent cohort is required before implementation for patients’ stratification.