Dose-response relationship between volume base dose and tumor local control in definitive radiotherapy for vaginal cancer.

OBJECTIVE: This study aimed to establish the dose-response relationship between volume base dose and tumor local control for vaginal cancer, including primary vaginal cancer and recurrent gynecologic malignancies in the vagina. MATERIALS AND METHODS: We identified studies that reported volume base dose and local control by searching the PubMed, the Web of Science, and the Cochrane Library Database through August 12, 2023. The regression analyses were performed using probit model between volume based dose versus clinical outcomes. Subgroup analyses were performed according to stratification: publication year, country, inclusion time of patients, patients with prior radiotherapy, age, primaries or recurrent, tumor size, concurrent chemoradiotherapy proportion, dose rate, image modality for planning, and interstitial proportion. RESULTS: A total of 879 patients with vaginal cancer were identified from 18 studies. Among them, 293 cases were primary vaginal cancer, 573 cases were recurrent cancer in the vagina, and 13 cases were unknown. The probit model showed a significant relationship between the HR-CTV (or CTV) D90 versus the 2-year and 3-year local control, P values were 0.013 and 0.014, respectively. The D90 corresponding to probabilities of 90% 2-year local control were 79.0 GyEQD2,10 (95% CI: 75.3-96.6 GyEQD2,10). CONCLUSIONS: A significant dependence of 2-year or 3-year local control on HR-CTV (or CTV) D90 was found. Our research findings encourage further validation of the dose-response relationship of radical radiotherapy for vaginal cancer through protocol based multicenter clinical trials.

Prevalence of trauma history and symptoms in patients who have received vaginal brachytherapy as part of their endometrial cancer treatment.

OBJECTIVE: Vaginal brachytherapy (VBT) is an essential component of curative intent treatment for many patients with endometrial cancer. The prevalence of trauma history in this population is unknown and important to understand considering VBT requires patients to have an instrument vaginally inserted while in the vulnerable lithotomy position. We aim to identify patients treated with intracavitary VBT and collect survey data to assess trauma endpoints. METHODS: We retrospectively identified patients with endometrial cancer who underwent intracavitary VBT at our institution between 01/2017 and 08/2022. Patients were mailed and/or electronically mailed a survey that included demographics, psychosocial background, and validated trauma surveys to be filled out as they relate to their trauma experiences prior to VBT and again considering any trauma symptomatology related to VBT. Electronic medical record review was performed. Descriptive statistics as well as multivariate analysis were performed. RESULTS: 206 patients met inclusion criteria, 66 (32.1%) of whom returned the survey and were included for analysis. Thirty-two percent of patients self-reported a personal history of any prior mental health diagnosis. Eighty-eight percent of patients screened positive for a history of trauma exposure, 23% endorsed symptoms of PTSD related to their VBT experience, and 5% screened positive for a likely PTSD diagnosis from VBT. CONCLUSION: A majority of included patients had a history of trauma exposure prior to VBT. In a subset of patients, VBT re-induced trauma and was considered to be an independent traumatic event. This study highlights the importance of practicing trauma informed care, particularly in this patient population.

Vulvovaginal Atrophy Following Treatment for Oncogynecologic Pathologies: Etiology, Epidemiology, Diagnosis, and Treatment Options.

Vulvovaginal atrophy, characterized by the thinning of vaginal mucosa typically resulting from reduced estrogen levels, is frequently exacerbated by oncogynecologic treatments such as chemotherapy, hormonal therapy, radiotherapy, or surgery. This condition significantly impacts the quality of life for cancer survivors, leading to persistent discomfort, heightened infection risk, and negative effects on sexual function and self-esteem. Despite being a relatively common complication, vulvovaginal atrophy is not always discussed before the start of treatment. Treatments typically mirror those used for natural menopause; however, efficacy and safety data specific to this population are limited due to the exclusion of these patients from clinical trials. A major safety concern is the risk of hormone-sensitive cancer recurrence associated with estrogen therapy, which drives a preference for non-hormonal alternatives. Newer treatments, such as laser therapy, radiofrequency, and vaginal injections, show promise with minimal side effects and hormone-independent mechanisms, though efficacy data varies, highlighting the need for further research. This narrative review explores the epidemiology, risk factors, diagnosis, and management of vulvovaginal atrophy after the treatment for oncogynecologic disorders.

Topical estrogen, testosterone, and vaginal dilator in the prevention of vaginal stenosis after radiotherapy in women with cervical cancer: a randomized clinical trial.

BACKGROUND: We aimed to evaluate the effects of different therapeutic options to prevent the evolution of vaginal stenosis after pelvic radiotherapy in women with cervical cancer. METHODS: open-label randomized clinical trial of 195 women, stage I-IIIB, aged 18-75 years, using topical estrogen (66), topical testosterone (34), water-based intimate lubricant gel (66), and vaginal dilators (29) to assess the incidence and severity of vaginal stenosis after radiotherapy at UNICAMP-Brazil, from January/2013 to May/2018. The main outcome measure was vaginal stenosis assessed using the Common Terminology Criteria for Adverse Events (CTCAE) scale and percental changes in vaginal volume. The women were evaluated at four different times: shortly after the end of radiotherapy, and four, eight, and 12 months after the beginning of the intervention. Statistical analysis was carried out using Symmetry test, Kruskal-Wallis test and multiple regression. RESULTS: the mean age of women was 46.78 (±13.01) years, 61,03% were premenopausal and 73,84% had stage IIB-IIIB tumors. The mean reduction in vaginal volume in the total group was 25.47%, with similar worsening in the four treatment groups with no statistical difference throughout the intervention period. There was worsening of vaginal stenosis evaluated by CTCAE scale after 1 year in all groups (p < 0.01), except for the users of vaginal dilator (p = 0.37). CONCLUSIONS: there was a reduction in vaginal volume in all treatment groups analyzed, with no significant difference between them. However, women who used vaginal dilators had a lower frequency and severity of vaginal stenosis assessed by the CTCAE scale after one year of treatment. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials, RBR-23w5fv . Registered 10 January 2017 - Retrospectively registered.

Vaginal necrosis: A rare late toxicity after radiation therapy.

Vaginal necrosis is a late radiation tissue injury with serious morbidity complications. It is rare, and its incidence is not well assessed in prospective trials. Patient comorbidities and radiation dose can significantly increase the risk. As treatment of gynecologic malignancies often involve a multidisciplinary approach, timely diagnosis and appropriate management by physicians of the team are crucial. Untreated vaginal necrosis can lead to infection, hemorrhage, necrosis-related fistulation to the bladder or rectum, perforation, and death. In this review, we describe the pathophysiology of vaginal necrosis, its clinical course, and management options.

The first major complication due to laser treatment for stress urinary incontinence: a short report.

AIM: Stress urinary incontinence (SUI) is a common benign disease causing a markedly negative impact on quality of life. Vaginal laser is a minimally invasive treatment and no major complications of this technique have been published to date. The purpose of the article is to present the first major adverse event related to this treatment. MATERIALS AND METHODS: We present the case of a 48-year-old woman with an important complication after vaginal laser for SUI. RESULTS: The patient presented a transverse vaginal septum and shortening of vaginal length after two sessions of vaginal erbium:yttrium aluminum garnet laser treatment. She required two surgical interventions, local injections, and pelvic floor physiotherapy, although currently the patient has not experienced complete resolution of symptoms. DISCUSSION AND CONCLUSIONS: Vaginal laser use can lead to serious adverse events. Selection of patients and treatment must be carried out with caution.

Vaginal Dilator and Pelvic Floor Exercises for Vaginal Stenosis, Sexual Health and Quality of Life among Cervical Cancer Patients Treated with Radiation: Clinical Report.

This clinical report aimed to evaluate the effectiveness of the combination of vaginal dilator (VD) and pelvic floor muscle exercises (PFME) on vaginal stenosis, sexual health and quality of life among women undergoing radiotherapy treatment for cervical cancer; PFME were instructed prior to radiotherapy with six-month follow-up. An intention-to-treat analysis was performed for the 28 women. At four-months after radiotherapy, most of the women (90.9%) maintained/increased one size of the VD and were sexually active (81.8%). Adherence to VD was high. Regarding quality of life, there was more limitation in emotional functioning. VD and PFME were effective at preventing stenosis.

DW-MRI predictive factors for radiation-induced vaginal stenosis in patients with cervical cancer.

AIM: To find diffusion-weighted (DW) magnetic resonance imaging (MRI) parameters predictive for radiation-induced vaginal stenosis (VS) in locally advanced cervical cancer (LACC) treated with neoadjuvant chemoradiation therapy (CRT). MATERIALS AND METHODS: Retrospective analysis of 43 patients with LACC who underwent 1.5 T DW-MRI before (baseline), after 2 weeks (early), and at the end of CRT (final). At MRI, vaginal length, thickness, width, and cervical tumour volume (TV) were measured. Vaginal signal intensity at DW-MRI was analysed at final MRI. CRT-induced VS was graded using Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Correlations between DW-MRI and clinical data were made using Wilcoxon's test, Mann-Whitney test, Fisher's exact test, or chi-squared test as appropriate. Receiver operating characteristic (ROC) curves were generated for variables to evaluate diagnostic ability to predict CRT-induced VS using a logistic regression model. RESULTS: Asymptomatic vaginal toxicity (CTCAE Grade 1) was observed in 14 patients and symptomatic CRT-induced VS (CTCAE Grade ≥2) was detected in 29 patients. Baseline TV was higher in Grade 1 than in Grade ≥2 (p=0.013). Median vaginal length, thickness, and width decreased between baseline and final MRI in all patients (p<0.0001) without significant variances between CTCAE grades. Significant differences were observed in DW-MRI patterns (p<0.0001). In Grade ≥2, DWI showed signal loss of vaginal mucosa in 17 patients (63%) and diffuse restricted diffusion of vaginal wall in eight patients (30%). AUC was 0.938 (coefficient=4.72; p<0.001) for DWI and 0.712 (coefficient=-2.623×10 -5; p=0.004) for TV. CONCLUSIONS: This is the first study using DW-MRI for predicting CRT-induced VS. DWI is useful tool in patients with LACC after CRT for early prevention and management strategies for VS.

At-Home Transvaginal Device Following Fractional Carbon Dioxide Laser Treatment for Genitourinary Syndrome of Menopause.

BACKGROUND: Device-based therapeutic approaches have been developed to treat women’s genitourinary post-menopausal symptoms. Fractional carbon dioxide laser resurfacing (FxCO2) has been demonstrated to be safe and effective in the treatment of GSM symptoms, however the results begin to wane by 12-months post-treatment. OBJECTIVE: This study aims at assessing the application of an at-home transvaginal red and infrared light device as a maintenance treatment commencing 12 months following FxCO2 laser treatment for genitourinary syndrome of menopause (GSM). STUDY DESIGN: Subjects completing 12-month follow-up after three fractional CO2 laser vulvovaginal treatments received an at-home device and monitored for GSM symptoms with long-term follow-up to 12 months (2 years post-laser). METHODS: 10 post-menopausal subjects completing 12-months follow-up after three FxCO2 vulvovaginal treatments for GSM were treated with an at-home red and infrared LED device. Treatment consisted of intravaginal application three times per week, and subjects were followed to 1, 3, 6, and 12 months. Subjects completed the vaginal assessment scale subject satisfaction, and QUID to assess for vulvovaginal and stress urinary incontinence (SUI) symptoms. RESULTS: Vulvovaginal symptoms measured by VAS were mean 89% improved at 12-month follow-up after FxCO2 and maintained at 73% improved over baseline (2 years post-laser) following an additional 12 months of at-home transvaginal light therapy (P<0.05). VAS symptoms gradually increased over the 12 months maintenance period by a mean of 17% (P<0.05). Mean subject satisfaction was 0 at baseline, 1.86 at 1 year following FxCO2, and 1.00 after an additional 1 year of at-home light therapy. SUI symptoms as measured by QUID were mean 81% improved at 12-month follow-up after FxCO2and maintained at 38% improved over baseline (2 years post-laser) following an additional 12-months of at-home light therapy (P<0.05). SUI symptoms gradually increased by a mean of 43% over the 12-month maintenance period (P<0.05). CONCLUSIONS: At-home transvaginal red and near infrared light therapy commencing at 12 months post-FxCO2 vulvovaginal treatment in a post-menopausal population maintained statistically significant improvements in vulvovaginal and SUI symptoms over the additional12-month period (2 years post-laser); however, a gradual return of symptoms suggests that laser re-treatment or combination withhormone therapy may be necessary to maintain optimal outcomes.J Drugs Dermatol. 2020;19(11):1076-1079. doi:10.36849/JDD.2020.1012.

Intravaginal energy-based devices and sexual health of female cancer survivors: a systematic review and meta-analysis.

A systematic review and meta-analysis was undertaken to assess the efficacy and safety of intravaginal energy-based therapies (laser and radiofrequency) on sexual health of cancer survivors (CS) (breast cancer (BCS) and/or gynecological cancer (GCS)). PubMed, Scopus, Web of Science, and Cochrane Library were searched until 21/02/2019. Quality of reporting, methodology, and body of evidence were assessed using STROBE, MINORS, and GRADE. Primary outcomes were dyspareunia, dryness, and sexual health (FSFI, FSDS-R). Secondary outcomes were burning, itching, dysuria, incontinence, Vaginal Health Index Score (VHIS), microbiome-cytokine evaluation, and adverse events. Main analyses, subgroup analyses, and sensitivity analyses were performed. Eight observational studies (n = 274) were eligible for inclusion. None of the studies evaluated radiofrequency. BCS and BCS-GCS were included in 87% and 13% of studies, respectively. All primary outcomes improved significantly with the exception of FSDS-R (dyspareunia (5 studies (n = 233), standardized mean difference (StdMD) (- 1.17), 95%CI [- 1.59, - 0.75]; p < 0.001; I2 = 55%), vaginal dryness (4 studies (n = 183), StdMD (- 1.98), 95%CI [- 3.31, - 0.65]; p = 0.003; I2 = 91%), FSFI (2 studies, n = 28, MD (12.79), 95%CI [7.69, 17.89]; p < 0.001; I2 = 0%). Itching, dysuria, and VHIS increased significantly, while burning was not improved. Serious adverse events were not observed by any of the studies. Intravaginal laser therapies appear to have a positive effect on dyspareunia, vaginal dryness, and FSFI of CS. However, the quality of evidence is "very low," with no data on intravaginal radiofrequency therapy. Further research with high-quality RCTs and long-term follow-up is needed to evaluate the value of energy-based devices as a therapeutic option for CS with sexual problems.

The impact of vaginal dilator use on vaginal stenosis and sexual quality of life in women treated with adjuvant radiotherapy for endometrial cancer.

BACKGROUND: Despite a lack of evidence and low compliance, current guidelines recommend the use of a vaginal dilator (VD) after pelvic radiotherapy (RT). We analyzed the effect of VD on vaginal stenosis (VS) and its influence on sexual quality of life (QoL) in women treated with adjuvant RT for endometrial cancer (EC). METHODS: Between 2014 and 2015, 56 consecutive patients were instructed to use a VD after completion of treatment. The maximum diameter of the comfortably introducible VD was measured before and at 1 year after treatment. The degree of VS was evaluated clinically, and sexual QoL was assessed with the European Organisation for Research and Treatment of Cancer (EORTC) sexual functioning items before RT, during RT, at 6 weeks, and at 1 year after RT. RESULTS: One year after RT, mean VD diameter had decreased by 2.7 ± 3.2 mm (p < 0.001) and 36 patients (64.3%) had clinical VS (grade I-III). A larger decrease in VD diameter correlated with a higher degree of clinical VS (p < 0.001). VD use (p = 0.81), RT modality (p = 0.68), and adjuvant ChT (p = 0.87) had no influence on VD diameter. Sexual activity decreased during RT and increased beyond pre-RT values 1 year after RT (p < 0.001). Sexual enjoyment decreased continuously during and after completion of RT (p = 0.013) and was influenced negatively by a higher degree of clinical VS (p = 0.01). CONCLUSION: Almost two thirds of patients developed clinical VS 1 year after adjuvant RT for EC, and sexual enjoyment was substantially reduced by VS. The use of a VD after RT may not serve to prevent sexual impairments and VS.

Sex steroid hormone receptor expression in the vaginal wall in cervical cancer survivors after radiotherapy.

Background: Sex steroid hormones and their receptors are important in female sexual function. The aim of this study was to investigate the expression and distribution of estrogen receptor (ER)α, ERß, G-protein-coupled ER-1 (GPER), androgen receptor (AR), progesterone receptor (PR)A, PRB and connective tissue growth factor (CTGF) in the vaginal wall among women who had been treated for cervical cancer with radiotherapy. Material and methods: We included cervical cancer survivors treated with radiotherapy and premenopausal control women of the same age scheduled for benign gynecological surgery. We analyzed the expression and distribution of sex steroid hormone receptors and CTGF in biopsies from the vaginal wall, by real-time PCR and immunohistochemistry (IHC). Serum samples were analyzed for hormone levels and radiation dose at biopsy site were calculated and correlated to levels of the sex steroid hormone receptors. Results: In the cervical cancer survivors (n = 34), we found a lower expression of ERα at both mRNA and protein levels, compared to the control women (n = 37). In the survivors with high radiation dose at biopsy site, the immunostaining of ERα and AR was lower in the epithelium and the stroma, compared to survivors with minimal radiation dose. The later group showed expression of ERα comparable to the control women. The cancer survivors were sufficiently substituted with systemic estradiol with no difference in the serum estradiol levels compared to control women. Conclusions: We found that external radiation reduces the ERα and AR protein expression in the vaginal mucosa, indicating that the vaginal changes in irradiated cervical cancer survivors and the lack of response to hormonal treatment could be due to the decreases in sex steroid hormone receptor expression.

Extended duration of dilator use beyond 1 year may reduce vaginal stenosis after intravaginal high-dose-rate brachytherapy.

BACKGROUND: Vaginal dilators (VD) are recommended following vaginal or pelvic radiotherapy for patients with endometrial carcinoma (EC) to prevent vaginal stenosis (VS). The time course of VS is not fully understood and the optimal duration of VD use is unknown. METHODS: We reviewed 243 stage IA-II EC patients who received adjuvant brachytherapy (BT) at an academic tertiary referral center. Patients were instructed to use their VD three times per week for at least 1-year duration. The primary outcome was development of grade ≥ 1 VS using CTCAEv4 criteria during the follow-up period. The log-rank test and multivariable Cox proportional hazards modeling were used to evaluate the effect of VD use (noncompliance vs. standard compliance [up to 1 year] vs. extended compliance [over 1 year]) on VS. RESULTS: The median follow-up was 15.2 months over the 5-year study period. At 15 months, the incidence of VS was 38.8% for noncompliant patients, 33.5% for those with standard compliance, and 21.4% for those with extended compliance (median time to grade ≥ 1 VS was 17.5 months, 26.7 months, and not yet reached for these groups, respectively). On multivariable Cox regression analysis, extended compliance remained a significant predictor of reduced VS risk when compared to both noncompliance (HR 0.38, 95% CI 0.18-0.80, p = 0.012) and standard compliance (HR 0.43, 95% CI 0.20-0.89, p = 0.023). CONCLUSIONS: The risk of VS persists beyond 1 year after BT. Extended VD compliance beyond 1 year may mitigate this risk.

Blue light-emitting diode in healthy vaginal mucosa-a new therapeutic possibility.

A healthy female genital mucosa has an ecosystem that remains in balance through interactions between endogenous and exogenous factors. The light-emitting diode (LED) is a device that emits light at different wavelengths, with varying color and effects. Blue light in humans is most commonly used for antimicrobial purposes and has been already applied to treat facial acne and gastric bacteria. Although blue LED therapy in humans has been reported, its properties against vaginal infections have not yet been investigated. This study aims to test the safety and effects of 401 ± 5 nm blue LED on healthy vaginal mucosa. Phase I clinical trial involving 10 women between 18 and 45 years old with healthy vaginal mucosa. The participants were illuminated by 401 ± 5 nm blue LED for 30 min and anamnesis, oncotic cytology, and pH measurement were made again after 21/28 days of treatment. In the re-evaluation, adverse effects were investigated. The mean age was 27 ± 5.4 years and one of the women was excluded due to interruption of use of oral contraceptives. Oncotic cytology done before and after therapy showed that the composition of the microflora remained normal in all participants. Vaginal pH remained unchanged in eight of the women and had a reduction in one woman (5.0-4.0). No adverse effects were observed during or after illumination. 401 ± 5 nm blue LED did not generate any adverse effects or pathogenic changes in the microflora and vaginal pH. The effects of 401 ± 5 nm blue LED still need to be tested in vulvovaginal pathogens. Trial registration number: NCT03075046.

Quality of life and oncological outcome in endometrial cancer patients after vaginal brachytherapy: comparison of two dosing schemes.

PURPOSE: Vaginal brachytherapy reduces the risk of local recurrence and was shown to be equieffective in preventing vaginal vault recurrence, but less toxic compared to external-beam radiotherapy in a subset of high intermediate-risk endometrial cancer patients and is administered as single adjuvant treatment in those patients. Different radiotherapeutic approaches with various dosing schemes exist toward brachytherapy. The aim of this study was to compare the outcome and long-term quality of life after brachytherapy with two different high-dose-rate dosing schemes. METHODS: Retrospective analysis was conducted of the recurrence and survival rates of 104 patients with endometrial cancer FIGO stage I-II that underwent adjuvant brachytherapy with three times 5 Gy or four times 5 Gy to the upper two-thirds of the vaginal vault in two different institutions between January 2010 and December 2013. Quality of life was assessed by EORTC QLQ-30 questionnaire and EN 24 module. RESULTS: The vaginal vault recurrence rates were 4.9% and 5.0% for patients treated with 3 × 5 Gy and 4 × 5 Gy, respectively (p = 0.98). We did not observe a difference in pelvic recurrence (p = 0.96), overall survival (p = 0.33) or quality of life between the different radiotherapy regimens. Metastatic recurrence and the use of chemotherapy contribute to impairment on quality of life. Younger patients (< 70 years) reported worse emotional functioning (p = 0.02) and higher symptom scales of diarrhea (p = 0.01) and financial problems (p = 0.03). Sexual activity was lower in patients younger than 70 years (p = 0.05). CONCLUSIONS: Further prospective studies are needed to evaluate the effect of dosing schemes on recurrence rates and quality of life. Younger patients (< 70 years) seem to experience greater reduction in quality of life due to endometrial cancer diagnosis.

Treatment to External Labia and Vaginal Canal With CO2 Laser for Symptoms of Vulvovaginal Atrophy in Postmenopausal Women.

Background: Increasingly, women have sought alternatives to traditional options (lubricants, estrogen products, and hormone replacement therapy) for unwelcome vaginal changes of menopause. Objectives: This study evaluated whether a series of three monthly fractional CO2 laser treatments significantly improves and maintains vaginal health indices of elasticity, fluid volume, pH level, epithelial integrity, and moisture. Self-reported symptoms of vaginal atrophy were also measured. Biopsy samples after a series of three treatments were evaluated for histological changes to vaginal canal tissue. Methods: Forty postmenopausal women were treated extravaginally and internally with a fractional CO2 laser. Objective measurements of vaginal health index, as well as subjective measurements of symptoms of vulvovaginal atrophy (VVA), urinary incontinence, and sexual function were reported at baseline. Follow-up evaluations were at one, three, six, and 12 months after the third treatment. Results: Vaginal health index improved significantly after the first treatment and was maintained with mean improvement of 9.6 ± 3.3 (P < 0.001) and 9.5 ± 3.3 (P < 0.001) at the 6- and 12-month follow ups, respectively. Vaginal symptoms of dryness, itching, and dyspareunia improved significantly (P < 0.05) at all evaluations. Histological findings showed increased collagen and elastin staining, as well as a thicker epithelium with an increased number of cell layers and a better degree of surface maturation. Conclusions: Fractional CO2 laser treatments were well tolerated and were associated with improvement in vaginal health and amelioration of symptoms of VVA. Histological changes in the epithelium and lamina propria, caused by fractional CO2 laser treatments, correlated with clinical restoration of vaginal hydration and pH to premenopausal levels.

Ten-year results of the PORTEC-2 trial for high-intermediate risk endometrial carcinoma: improving patient selection for adjuvant therapy.

BACKGROUND: PORTEC-2 was a randomised trial for women with high-intermediate risk (HIR) endometrial cancer, comparing pelvic external beam radiotherapy (EBRT) with vaginal brachytherapy (VBT). We evaluated long-term outcomes combined with the results of pathology review and molecular analysis. METHODS: 427 women with HIR endometrial cancer were randomised between 2002-2006 to VBT or EBRT. Primary endpoint was vaginal recurrence (VR). Pathology review was done in 97.4%, combined with molecular analysis. RESULTS: Median follow-up was 116 months; 10-year VR was 3.4% versus 2.4% for VBT vs. EBRT (p = 0.55). Ten-year pelvic recurrence (PR) was more frequent in the VBT group (6.3% vs. 0.9%, p = 0.004), mostly combined with distant metastases (DM). Ten-year isolated PR was 2.5% vs. 0.5%, p = 0.10, and DM 10.4 vs. 8.9% (p = 0.45). Overall survival for VBT vs. EBRT was 69.5% vs. 67.6% at 10 years (p = 0.72). L1CAM and p53-mutant expression and substantial lymph-vascular space invasion were risk factors for PR and DM. EBRT reduced PR in cases with these risk factors. CONCLUSION: Long-term results of the PORTEC-2 trial confirm VBT as standard adjuvant treatment for HIR endometrial cancer. Molecular risk assessment has the potential to guide adjuvant therapy. EBRT provided better pelvic control in patients with unfavourable risk factors.

Radiotherapy for cervical cancer - impact on the vaginal epithelium and sexual function.

BACKGROUND: Women who have been treated for cervical cancer have persistent changes in their sexual function, which result in considerable distress. The aim of this study was to investigate the morphology of the vaginal epithelium in cervical cancer survivors treated with radiotherapy and its correlation to serum levels of sex steroid hormones and sexual function. MATERIAL AND METHODS: We included 34 patients treated for cervical cancer with radiotherapy and 37 healthy age-matched control women scheduled for benign gynecological surgery. After inspection and grading of vaginal atrophy, vaginal biopsies were taken. Epithelial structures were analyzed by measuring epithelial thickness as well as the number, height and width of the dermal papillae and the dermal papillae distance. Sex steroid hormone levels were analyzed and a questionnaire designed to assess sexual function was filled out. RESULTS: In the cervical cancer survivors treated with radiotherapy, the vaginal epithelium volume was reduced compared to control women. Longer distance between the dermal papillae (p < .001) and a shorter distance from basal layer to epithelial surface (p < .05) were measured. Mucosal atrophy was observed in 91% of the survivors. There was no difference in serum estradiol between cancer survivors and control women, implying that the cancer survivors were sufficiently substituted. The epithelial thickness correlated to serum levels of estradiol. The cervical cancer survivors reported more physical sexual symptoms. The highest relative risk (RR) was found for insufficient vaginal lubrication (RR 12.6), vaginal inelasticity (RR 6.5), reduced genital swelling when sexually aroused (RR 5.9), and for reduction of vaginal length during intercourse (RR 3.9). CONCLUSION: We found that cervical cancer treatment including radiotherapy is associated with vaginal epithelial atrophy and sexual dysfunction. To hamper the atrophic process affecting the sexual function, an early start of local estrogen after therapy might be of importance.

Fractional CO2 laser treatment for vaginal laxity: A preclinical study.

BACKGROUND AND OBJECTIVE: Various studies have investigated treatment for vaginal laxity with microablative fractional carbon dioxide CO2 laser in humans; however, this treatment has not yet been studied in an animal model. Herein, we evaluate the therapeutic effects of fractional CO2 laser for tissue remodeling of vaginal mucosa using a porcine model, with the aim of improving vaginal laxity. STUDY DESIGN/MATERIALS AND METHODS: The fractional CO2 laser enables minimally invasive and non-incisional procedures. By precisely controlling the laser energy pulses, energy is sent to the vaginal canal and the introitus area to induce thermal denaturation and contraction of collagen. We examined the effects of fractional CO2 laser on a porcine model via clinical observation and ultrasound measurement. Also, thermal lesions were histologically examined via hematoxylin-eosin staining, Masson's trichrome staining, and Elastica van Gieson staining and immunohistochemistry. RESULTS: The three treatment groups, which were determined according to the amount of laser-energy applied (60, 90, and 120 mJ), showed slight thermal denaturation in the vaginal mucosa, but no abnormal reactions, such as excessive hemorrhaging, vesicles, or erythema, were observed. Histologically, we also confirmed that the denatured lamina propria induced by fractional CO2 laser was dose-dependently increased after laser treatment. The treatment groups also showed an increase in collagen and elastic fibers due to neocollagenesis and angiogenesis, and the vaginal walls became firmer and tighter because of increased capillary and vessel formation. Also, use of the fractional CO2 laser increased HSP (heat shock protein) 70 and collagen type I synthesis. CONCLUSION: Our results show that microablative fractional CO2 laser can produce remodeling of the vaginal connective tissue without causing damage to surrounding tissue, and the process of mucosa remodeling while under wound dressings enables collagen to increase and the vaginal wall to become thick and tightened. Lasers Surg. Med. 50:940-947, 2018. © 2018 Wiley Periodicals, Inc.

Histologic and Clinical Changes in Vulvovaginal Tissue After Treatment With a Transcutaneous Temperature-Controlled Radiofrequency Device.

BACKGROUND: Although transcutaneous temperature-controlled radiofrequency (TTCRF) may effectively treat vulvovaginal laxity (VVL), atrophic vaginitis (AV), orgasmic dysfunction (OD), and stress urinary incontinence (SUI), there is a lack of histopathologic evidence to validate its use. OBJECTIVE: Evaluate clinical and histological changes induced by vulvovaginal TTCRF. MATERIALS AND METHODS: This was a prospective, nonrandomized trial. Ten female subjects with mild-to-moderate VVL, with or without AV, OD, and/or SUI underwent 3 TTCRFs at 4-week intervals. Five subjects underwent pre- and post-treatment biopsies of the labia majora and vaginal canal for histology. Assessments were performed at baseline and Days 10, 30, 60, and 120. RESULTS: Investigator-rated VVL improved significantly from baseline to Day 10, with improvement maintained through Day 120 (p = .001 and .001, respectively). Sexual satisfaction improved significantly by Day 60 (p = .001). Improvement in AV reached significance at Day 120 (p = .048). Although OD and SUI improved steadily, the difference in improvement did not reach statistical significance. Histology revealed that post-treatment increases in collagen, elastin, vascularity, and small nerve fibers. CONCLUSION: Transcutaneous temperature-controlled RF resulted in significant improvements in AV, VVL, and sexual satisfaction with milder improvements in OD and SUI. Post-treatment histology demonstrated neocollagenesis, neoelastogenesis, neoangiogenesis, and the first reported finding of TTCRF-related neurogenesis.