Whole-Body Vibration Prevents Neuronal, Neurochemical, and Behavioral Effects of Morphine Withdrawal in a Rat Model.

Peripheral mechanoreceptor-based treatments such as acupuncture and chiropractic manipulation have shown success in modulating the mesolimbic dopamine (DA) system originating in the ventral tegmental area (VTA) of the midbrain and projecting to the nucleus accumbens (NAc) of the striatum. We have previously shown that mechanoreceptor activation via whole-body vibration (WBV) ameliorates neuronal and behavioral effects of chronic ethanol exposure. In this study, we employ a similar paradigm to assess the efficacy of WBV as a preventative measure of neuronal and behavioral effects of morphine withdrawal in a Wistar rat model. We demonstrate that concurrent administration of WBV at 80 Hz with morphine over a 5-day period significantly reduced adaptations in VTA GABA neuronal activity and NAc DA release and modulated expression of δ-opioid receptors (DORs) on NAc cholinergic interneurons (CINs) during withdrawal. We also observed a reduction in behavior typically associated with opioid withdrawal. WBV represents a promising adjunct to current intervention for opioid use disorder (OUD) and should be examined translationally in humans.

A general framework to develop a radiomic fingerprint for progression-free survival in cervical cancer.

PURPOSE: Treatment of locally advanced cervical cancer patients includes chemoradiation followed by brachytherapy. Our aim is to develop a delta radiomics (DRF) model from MRI-based brachytherapy treatment and assess its association with progression free survival (PFS). MATERIALS AND METHODS: A retrospective analysis of FIGO stage IB- IV cervical cancer patients between 2012 and 2018 who were treated with definitive chemoradiation followed by MRI-based intracavitary brachytherapy was performed. Clinical factors together with 18 radiomic features extracted from different radiomics matrices were analyzed. The delta radiomic features (DRFs) were extracted from MRI on the first and last brachytherapy fractions. Support Vector Machine (SVM) models were fitted to combinations of 2-3 DRFs found significant after Spearman correlation and Wilcoxon rank sum test statistics. Additional models were tested that included clinical factors together with DRFs. RESULTS: A total of 39 patients were included in the analysis with a median patient age of 52 years. Progression occurred in 20% of patients (8/39). The significant DRFs using two DRF feature combinations was a model using auto correlation (AC) and sum variance (SV). The best performing three feature model combined mean, AC & SV. Additionally, the inclusion of FIGO stages with the 2- and 3 DRF combination model(s) improved performance compared to models with only DRFs. However, all the clinical factor + DRF models were not significantly different from one another (all AUCs were 0.77). CONCLUSIONS: Our study shows promising evidence that radiomics metrics are associated with progression free survival in cervical cancer.

Considerations for pharmacologic thromboprophylaxis following inpatient brachytherapy for gynecologic malignancies.

PURPOSE: Brachytherapy irradiation carries risks of both bleeding and venous thromboembolism (VTE). No screening or management recommendations for VTE in this setting have been developed. Our study aims to understand the incidence of VTE, compile published anticoagulation guidelines, and call for future guidelines to address thromboprophylaxis in this population. METHODS AND MATERIALS: A retrospective, single institution study of patients undergoing brachytherapy irradiation between 2012 and 2022 was undertaken. We analyzed 2 cohorts: 87 patients undergoing brachytherapy with an inpatient admission, and 66 patients assessed for risk of VTE or bleeding after discharge from an inpatient admission for brachytherapy. Caprini risk scores were calculated for each patient, and statistical analyses were performed. RESULTS: Eighty-seven patients were included, and 25% had a VTE diagnosis. Forty-seven (54%) of patients included underwent brachytherapy as definitive treatment of cervical cancer, and 16 (18%) received brachytherapy irradiation to treat recurrent endometrial cancer. In the cohort of 66 patients assessed for risk of VTE or bleeding after brachytherapy discharge, 23 (34.8%) were discharged with thromboprophylaxis, and 43 (65.2%) were discharged without thromboprophylaxis. None of the patients discharged on thromboprophylaxis were diagnosed with a VTE within 90 days of discharge after brachytherapy, whereas 3 of 43 (7%) discharged without thromboprophylaxis were diagnosed with a VTE, OR and 95% CI: 0.25 (0.01-5.29), p = 0.37. Of the 23 patients discharged on thromboprophylaxis, 1 was readmitted for bleeding OR and 95% CI: 5.8 (0.22-155.18), p = 0.29. The median Caprini score was 11. CONCLUSIONS: VTE is a common occurrence in patients undergoing brachytherapy. Patients undergoing brachytherapy irradiation who require inpatient admission represent a unique population, and specialty organizations should develop consensus recommendations to address these clinical challenges.

Overcoming Burnout and Promoting Wellness in Radiation Oncology: A Report From the ACR Commission on Radiation Oncology.

Burnout, defined by the presence of emotional exhaustion, depersonalization, and decreased sense of personal accomplishment, impacts a significant portion of radiation oncologists. This has been exacerbated by the COVID-19 pandemic, is notably worse for women, and has been identified as an international concern. Key contributors to burnout within radiation oncology include inadequate clinical and administrative support, imbalanced personal and professional lives including time with family and for self-care, decreased job satisfaction secondary to increased electronic medical record and decreased patient time, unsupportive organizational culture, lack of transparency from leadership and inclusion in administrative decisions, emotionally intensive patient interactions, challenges within the radiation oncology workforce, financial security related to productivity-based compensation and increasing medical training-related debt, limited education on wellness, and fear of seeking mental health services due to stigma and potential negative impacts on the trajectory of one's career. Limited data exist to quantify the impacts of these factors on the overall levels of burnout within radiation oncology specifically, and additional efforts are needed to understand and address root causes of burnout within the field. Strategies should focus on improving the systems in which physicians work and providing the necessary skills and resources to thrive in high-stress, high-stakes work environments.

Access to Radiation Therapy and Related Clinical Outcomes in Patients With Cervical and Breast Cancer Across Sub-Saharan Africa: A Systematic Review.

PURPOSE: To better understand the barriers to accessing standard-of-care radiation therapy (RT) for breast and cervical cancer in sub-Saharan Africa and their impact on outcomes. METHODS: A comprehensive literature search was completed with a medical librarian. Articles were screened by title, abstract, and full text. Included publications were analyzed for data describing barriers to RT access, available technology, and disease-related outcomes, and further grouped into subcategories and graded according to predefined criteria. RESULTS: A total of 96 articles were included: 37 discussed breast cancer, 51 discussed cervical cancer, and eight discussed both. Financial access was affected by health care system payment models and combined burdens of treatment-related costs and lost wages. Staffing and technology shortages limit the ability to expand service locations and/or increase capacity within existing centers. Patient factors including use of traditional healers, fear of stigma, and low health literacy decrease the likelihood of early presentation and completion of therapies. Survival outcomes are worse than most high- and middle-income countries and are affected by many factors. Side effects are similar to other regions, but these findings are limited by poor documentation capabilities. Access to palliative RT is more expeditious than definitive management. RT was noted to lead to feelings of burden, lower self-esteem, and worsened quality of life. CONCLUSION: Sub-Saharan Africa represents a diverse region with barriers to RT that differ on the basis of funding, available technology and staff, and community populations. Although long-term solutions must focus on building capacity by increasing the number of treatment machines and providers, short-term improvements should be implemented, such as interim housing for traveling patients, increased community education to reduce late-stage diagnoses, and use of virtual visits to avoid travel.

Mechanical Stimulation Alters Chronic Ethanol-Induced Changes to VTA GABA Neurons, NAc DA Release and Measures of Withdrawal.

Therapeutic activation of mechanoreceptors (MStim) in osteopathy, chiropractic and acupuncture has been in use for hundreds of years with a myriad of positive outcomes. It has been previously shown to modulate the firing rate of neurons in the ventral tegmental area (VTA) and dopamine (DA) release in the nucleus accumbens (NAc), an area of interest in alcohol-use disorder (AUD). In this study, we examined the effects of MStim on VTA GABA neuron firing rate, DA release in the NAc, and behavior during withdrawal from chronic EtOH exposure in a rat model. We demonstrate that concurrent administration of MStim and EtOH significantly reduced adaptations in VTA GABA neurons and DA release in response to a reinstatement dose of EtOH (2.5 g/kg). Behavioral indices of EtOH withdrawal (rearing, open-field crosses, tail stiffness, gait, and anxiety) were substantively ameliorated with concurrent application of MStim. Additionally, MStim significantly increased the overall frequency of ultrasonic vocalizations, suggesting an increased positive affective state.

Dopamine D2-Subtype Receptors Outside the Blood-Brain Barrier Mediate Enhancement of Mesolimbic Dopamine Release and Conditioned Place Preference by Intravenous Dopamine.

Dopamine (DA) is a cell-signaling molecule that does not readily cross the blood-brain barrier. Despite this, peripherally administered DA enhances DA levels in the nucleus accumbens and alters DA-related behaviors. This study was designed to investigate whether DA subtype-2 receptors are involved in the enhancement of nucleus accumbens (NAc) DA levels elicited by intravenous DA administration. This was accomplished by using microdialysis in the NAc and extracellular single unit recordings of putative DA neurons in the ventral tegmental area (VTA). Additionally, the reinforcing properties of intravenous DA were investigated using a place conditioning paradigm and the effects of intravenous DA on ultrasonic vocalizations were assessed. Following administration of intravenous dopamine, the firing rate of putative DA neurons in the VTA displayed a biphasic response and DA levels in the nucleus accumbens were enhanced. Pretreatment with domperidone, a peripheral-only DA D2 receptor (D2R) antagonist, reduced intravenous DA mediated increases in VTA DA neuron activity and NAc DA levels. Pretreatment with phentolamine, a peripheral α-adrenergic receptor antagonist, did not alter the effects of IV DA on mesolimbic DA neurotransmission. These results provide evidence for peripheral D2R mediation of the effects of intravenous DA on mesolimbic DA signaling.

Treatment of cervical cancer: overcoming challenges in access to brachytherapy.

INTRODUCTION: Brachytherapy is an essential component of the cervical cancer treatment paradigm as it contributes to improved clinical outcomes and overall survival. Yet brachytherapy remains globally underutilized, with disparities in access at both national and international levels. AREAS COVERED: The review explores current brachytherapy utilization practices and efforts being undertaken to address barriers to implementation in low-, middle-, and high-income countries, and how these efforts are projected to impact future brachytherapy access. The content presented is based on a review of published literature and the authors' collective clinical experiences. EXPERT OPINION: There exists a tremendous opportunity to expand access to essential brachytherapy services for women with cervical cancer. Many national and international brachytherapy efforts exist; yet it remains imperative that such focused efforts continue to grow and provide further access to this critical treatment modality for women in need worldwide.

The peripheral dopamine 2 receptor antagonist domperidone attenuates ethanol enhancement of dopamine levels in the nucleus accumbens.

BACKGROUND: Dopamine neuron firing in the ventral tegmental area (VTA) and dopamine release in the nucleus accumbens have been implicated in reward learning. Ethanol is known to increase both dopamine neuron firing in the VTA and dopamine levels in the nucleus accumbens. Despite this, some discrepancies exist between the dose of ethanol required to enhance firing in vivo and ex vivo. In the present study we investigated the effects of peripheral dopamine 2 subtype receptor antagonism on ethanol's effects on dopamine neurotransmission. METHODS: Plasma catecholamine levels were assessed following ethanol administration across four different doses of EtOH. Microdialysis and voltammetry were used to assess the effects of domperidone pretreatment on ethanol-mediated increases in dopamine release in the nucleus accumbens. A place conditioning paradigm was used to assess conditioned preference for ethanol and whether domperidone pretreatment altered this preference. Open-field and loss-of-righting reflex paradigms were used to assess the effects of domperidone on ethanol-induced sedation. A rotarod apparatus was used to assess the effects of domperidone on ethanol-induced motor impairment. RESULTS: Domperidone attenuated ethanol's enhancement of mesolimbic dopamine release under non-physiological conditions at intermediate (1.0 and 2.0 g/kg) doses of ethanol. Domperidone also decreased EtOH-induced sedation at 2.0 g/kg. Domperidone did not alter ethanol conditioned place preference nor did it affect ethanol-induced motor impairment. CONCLUSIONS: These results show that peripheral dopamine 2 receptors mediate some of the effects of ethanol on nonphysiological dopamine neurotransmission, although these effects are not related to the rewarding properties of ethanol.

Magnetic Resonance Guided Radiation Therapy for Pancreatic Adenocarcinoma, Advantages, Challenges, Current Approaches, and Future Directions.

INTRODUCTION: Pancreatic adenocarcinoma (PAC) has some of the worst treatment outcomes for any solid tumor. PAC creates substantial difficulty for effective treatment with traditional RT delivery strategies primarily secondary to its location and limited visualization using CT. Several of these challenges are uniquely addressed with MR-guided RT. We sought to summarize and place into context the currently available literature on MR-guided RT specifically for PAC. METHODS: A literature search was conducted to identify manuscript publications since September 2014 that specifically used MR-guided RT for the treatment of PAC. Clinical outcomes of these series are summarized, discussed, and placed into the context of the existing pancreatic literature. Multiple international experts were involved to optimally contextualize these publications. RESULTS: Over 300 manuscripts were reviewed. A total of 6 clinical outcomes publications were identified that have treated patients with PAC using MR guidance. Successes, challenges, and future directions for this technology are evident in these publications. MR-guided RT holds theoretical promise for the treatment of patients with PAC. As with any new technology, immediate or dramatic clinical improvements associated with its use will take time and experience. There remain no prospective trials, currently publications are limited to small retrospective experiences. The current level of evidence for MR guidance in PAC is low and requires significant expansion. Future directions and ongoing studies that are currently open and accruing are identified and reviewed. CONCLUSIONS: The potential promise of MR-guided RT for PAC is highlighted, the challenges associated with this novel therapeutic intervention are also reviewed. Outcomes are very early, and will require continued and long term follow up. MR-guided RT should not be viewed in the same fashion as a novel chemotherapeutic agent for which dosing, administration, and toxicity has been established in earlier phase studies. Instead, it should be viewed as a novel procedural intervention which must be robustly tested, refined and practiced before definitive conclusions on the potential benefits or detriments can be determined. The future of MR-guided RT for PAC is highly promising and the potential implications on PAC are substantial.

Impact of Concurrent Coincident Use of Metformin During Lung Stereotactic Body Radiation Therapy.

Introduction Recent data suggest synergy of chemoradiotherapy and metformin in locally-advanced non-small cell lung cancer (NSCLC). It remains unclear if similar synergy exists with stereotactic lung body radiation therapy (SBRT) and metformin. We analyzed the role of metformin on progression-free survival (PFS) and toxicity in the setting of lung SBRT. Methods We identified 31 patients on metformin-treated with SBRT for early-stage NSCLC. Eighty-nine similarly treated patients were chosen as controls. Kaplan-Meier method was used to estimate cumulative PFS probabilities. Results Median follow-up was 30.7 months. Forty-two patients had diabetes, 31 (74%) of which were taking metformin concurrent with SBRT. Median PFS for metformin-users vs. metformin non-users was 36.4 months vs 48.9 months, respectively (p = 0.29). Among diabetic patients, median PFS for metformin users was 36.4 months and was unobserved for non-users (p= 0.40). On univariable analysis, male sex (p = 0.03) and tumor size (p = 0.01) were associated with the risk of progression or death; use of metformin was not significant (p = 0.34). There was no difference in grade ≥2 radiation pneumonitis between metformin users vs non-users (p = 0.51) Conclusion In this retrospective sample of lung SBRT patients, we did not detect a meaningful effect of concurrent metformin use on PFS. Since SBRT and conventional RT may have different cell kill mechanisms, the previously described beneficial effects of metformin may not apply in a hypofractionated setting. These results should be validated in an independent dataset, and we await the results of ongoing clinical trials.

Pretreatment Factors Influencing Radiation Pneumonitis after Stereotactic Body Radiation Therapy in the Treatment of Lung Cancer.

Objective Radiation pneumonitis (RP) is a dose-limiting toxicity that affects the treatment of lung cancer. Data on factors predictive of developing symptomatic RP after stereotactic body radiation therapy (SBRT) are limited. We reviewed data to identify pretreatment factors predictive of the development of symptomatic RP in patients' lung cancer treated with SBRT. Methods Data were collected on 296 patients treated with SBRT for lung cancer. Factors available at time of consultation were analyzed for the development of symptomatic RP, defined as CTCAE v. 4.0 ≥ Grade 2. The factors analyzed included patient demographic, tumor-specific, and pretreatment pulmonary function data. Univariate and multivariate analyses were performed to assess for predictive factors. Results Median follow-up was 22 months. The rate of symptomatic RP was 16%. Univariate analysis showed an increased rate of symptomatic RP with treatments to the right lung (22% vs. 9%, p = 0.007), driven primarily by an increased rate of symptomatic RP when treating the right lower lobe (RLL) vs. other lobes (31 vs. 13%, p = 0.03). Patients with a history of prior lung directed therapy were also more likely to develop symptomatic RP (12% vs. 24%, p = 0.008). These statistical differences were retained on multivariate analysis. Conclusion SBRT to the right lung, especially the RLL, and to patients with a history of prior lung-directed therapy increases the risk of developing symptomatic RP after SBRT. Further studies on ways to predict and prevent symptomatic RP are needed.

Prognostic Significance of Nuclear Factor Kappa B Expression in Locally Advanced Cervical Cancer Patients Treated Definitively With Concurrent Chemoradiation.

OBJECTIVES: Nuclear factor kappa B (NFkB) is a transcription factor shown to confer treatment resistance in tumors. A previous report suggested an association between pretreatment NFkB and poorer outcomes for cervical cancer patients treated with chemoradiation therapy (CRT). We aimed to validate their findings in a larger patient cohort. MATERIALS AND METHODS: This Institutional Review Board approved study included patients with locally advanced cervical cancer patients treated with CRT. Evaluation of both nuclear and cytoplasmic immunoreactivity for NFkB was scored semiquantitatively by 3 pathologists. Cytoplasmic positivity incorporated both the intensity and percentage of immunoreactivity in invasive carcinoma (H-score), whereas nuclear positivity was assessed by percentage of positive cells. Outcomes were stratified by NFkB overexpression and tumor characteristics. Overall survival (OS), progression-free survival (PFS), distant metastases-free survival (DMFS), and local regional control (LC) were obtained using Kaplan-Meier and differences between groups were evaluated by the log-rank test. Hazard ratios were obtained using Cox regression for both univariate and multivariate analyses. RESULTS: The mean age was 51 years old and most (78.57%) had locally advanced disease. Five-year OS, PFS, LC, and DMFS in the entire cohort were 57.18% (confidence interval [CI], 34.06%-74.82%), 48.07% (CI, 25.50%-67.52%), 72.11% (CI, 49.96%-85.73%), and 62.85% (CI, 36.33%-80.82%), respectively. There was no significant association between NFkB expression (H-index ≥180) and 3-year and 5-year OS (P-value=0.34), PFS (P-value=0.21), LC (P-value=0.86), or DMFS (P-value=0.18). CONCLUSIONS: Our study demonstrated that cytoplasmic NFkB-p65 expression (H-index ≥180) was associated with a nonstatistically significant trend toward poor clinical outcomes in locally advanced cervical cancer patients treated definitively with CRT.

Monitoring ecological recovery of reclaimed wellsites: Protocols for quantifying recovery on forested lands.

We developed a scientifically robust and financially sustainable monitoring protocol to enable a consistent assessment of ecological recovery of physical, chemical, and biological indicators at certified reclaimed industrial wellsites in forested lands in noutheastern Alberta. Using the developed protocols, data can be generated from measurement of soil, vegetation, and landscape indicators at reclaimed wellsites and adjacent reference sites. We selected the appropriate vegetation, soil, and habitat indicators for a long-term reclamation monitoring program and have provided sampling protocols for the selected indicators here. The protocols may be used to identify and prioritize indicators of reduced ecosystem health and to track ecological recovery of reclaimed sites over time. The development of these integrated monitoring protocols is a first step towards successful and consistent long-term monitoring to assess ecological recovery of certified wellsites in Alberta. These protocols can be applied to wellsites and other similar sized disturbances in other forested regions too.

Predictors of Distant Failure After Stereotactic Body Radiation Therapy for Stages I to IIA Non-Small-Cell Lung Cancer.

PURPOSE: The use of stereotactic body radiation therapy (SBRT) has emerged as an effective treatment modality for patients with early-stage non-small-cell lung cancer (NSCLC), with excellent local control rates. Despite this, there is a predominant pattern of distant failure. We sought to identify factors that help predict which patients with stages I to IIA NSCLC treated with SBRT are at highest risk of distant failure, so that we may utilize these factors in the future to help determine which patients may benefit from the addition of systemic therapies. PATIENTS AND METHODS: We retrospectively reviewed 292 patients treated with SBRT for early stage NSCLC from 2006 to 2016 at 2 institutions. Patients were classified by T stage, tumor size, location and histology, pretreatment positron emission tomography/computed tomography (PET/CT) standardized uptake value (SUV), smoking status, and age. The primary endpoint of the study was distant failure. We aimed to analyze if patient characteristics could be identified that predicted for distant failure through the use of competing risk analysis. RESULTS: The median follow-up was 21.9 months. The median dose of radiation and fractionation delivered was 50 Gy (range, 45-65 Gy) in 5 fractions (range, 3-13 fractions). The median patient age was 72.8 years (interquartile range, 65.4-79.7 years). The 2-year distant failure was 22.0%, and overall survival at 2 years was found to be 61.0%. For every 1-year increase in patient age, the hazard of distant failure at any given time was 3% lower (hazard ratio, 0.97; 95% confidence interval, 0.94-0.99; P = .04). None of the remaining characteristics emerged as significant risk factors for distant failure on univariable or multivariable analysis. CONCLUSIONS: Overall, our cohort had distant failure and survival rates comparable with what has been described in the literature. Although we were unable to identify factors outside of age that correlated to risk of distant failure, this topic warrants further investigation, as distant failure is the primary pattern of failure with SBRT when used as the primary management for early-stage NSCLC. Additional molecular studies are needed to further inform on the role of systemic therapy in patients with early-stage NSCLC to improve clinical outcomes.

Impact on treatment time of MRI-based brachytherapy in two implants (4 doses) compared with CT-based brachytherapy in five implants for cervical cancer.

PURPOSE: Concurrent chemoradiotherapy and brachytherapy is the standard of care for locally advanced cervical cancer. Brachytherapy is an integral part of treatment and has improved overall survival. Research is needed to ascertain the planning modalities and schedules to best use resources and optimize treatment time course. We hypothesized that MRI-based brachytherapy when delivered with the described regimen would not prolong, and potentially shorten, overall treatment time as compared with CT-based brachytherapy. METHODS AND MATERIALS: This study was a single-institution retrospective review within the years 2008 through 2018. Patients with cervical cancer of any stage who underwent definitive chemoradiotherapy and either CT- or MRI-based brachytherapy were included. The primary outcome variable for this study was time (in days). Overall treatment time was defined as the number of days from the first until the last day of radiotherapy. Univariate analysis was performed using Stata statistical software. RESULTS: External beam radiotherapy doses were generally 45-50.4 Gy. CT-based and MRI-based brachytherapy were performed in 55 and 49 patients, respectively. The median treatment time for brachytherapy with CT-based planning was 19.0 days and with MRI-based planning was 9.0 days (p < 0.001). The median treatment time for total radiation therapy with CT-based planning was 53 days, and with MRI-based planning was 50 days (p = 0.781). CONCLUSIONS: This study found that MRI-based brachytherapy, when performed with the proposed regimen, did not prolong overall treatment time and significantly decreased time to complete brachytherapy in comparison with CT-based brachytherapy on nonconsecutive days. This regimen favorably impacts timely completion of treatment and uses MRI resources well within the construct of our institution.

Multi-institutional Analysis of Vaginal Brachytherapy Alone for Women With Stage II Endometrial Carcinoma.

PURPOSE: To investigate the survival endpoints in women with International Federation of Gynecology and Obstetrics (FIGO) stage II endometrial cancer who received adjuvant vaginal brachytherapy (VBT) alone using multi-institutional pooled data. METHODS AND MATERIALS: We performed a multi-institutional analysis of surgically staged patients with FIGO stage II endometrioid-type endometrial cancer treated with VBT alone. Patient, tumor, and treatment characteristics were collected and analyzed. Univariable and multivariable frailty survival models were performed to assess clinicopathologic risk factors for recurrence and death. RESULTS: One hundred six patients were included (92 VBT alone and 14 VBT with chemotherapy) with median follow-up of 39.0 months. Pelvic node dissection was performed in 89.6% of patients. One hundred four patients (98.1%) and 2 patients (1.9%) had microscopic and macroscopic cervical stromal invasion, respectively. Grade 1 or 2 disease occurred in 88.6% of patients. For patients treated with VBT without chemotherapy, the 5-year estimates of vaginal failure, pelvic nodal failure, and distant metastases were 2.6%, 4.2%, and 7.2%, respectively. Five-year progression-free survival and overall survival were 74.0% and 76.2%, respectively. On univariable and multivariable models for progression-free survival, increasing age and lack of pelvic node resection were hazardous (P < .05). CONCLUSIONS: Vaginal and pelvic failure rates were low in this selected population of stage II patients receiving adjuvant VBT without external beam radiation therapy. It is reasonable to consider adjuvant VBT alone in selected patients with grade 1 or 2 disease and microscopic cervical stromal invasion who underwent pelvic lymphadenectomy.