Speed of environmental change frames relative ecological risk in climate change and climate intervention scenarios.

Stratospheric aerosol injection is a potential method of climate intervention to reduce climate risk as decarbonization efforts continue. However, possible ecosystem impacts from the strategic design of hypothetical intervention scenarios are poorly understood. Two recent Earth system model simulations depict policy-relevant stratospheric aerosol injection scenarios with similar global temperature targets, but a 10-year delay in intervention deployment. Here we show this delay leads to distinct ecological risk profiles through climate speeds, which describe the rate of movement of thermal conditions. On a planetary scale, climate speeds in the simulation where the intervention maintains temperature are not statistically distinguishable from preindustrial conditions. In contrast, rapid temperature reduction following delayed deployment produces climate speeds over land beyond either a preindustrial baseline or no-intervention climate change with present policy. The area exposed to threshold climate speeds places different scenarios in context to their relative ecological risks. Our results support discussion of tradeoffs and timescales in future scenario design and decision-making.

MicroRNA-34a-Dependent Attenuation of Angiogenesis in Right Ventricular Failure.

BACKGROUND: The right ventricle (RV) is at risk in patients with complex congenital heart disease involving right-sided obstructive lesions. We have shown that capillary rarefaction occurs early in the pressure-loaded RV. Here we test the hypothesis that microRNA (miR)-34a, which is induced in RV hypertrophy and RV failure (RVF), blocks the hypoxia-inducible factor-1α-vascular endothelial growth factor (VEGF) axis, leading to the attenuated angiogenic response and increased susceptibility to RV failure. METHODS AND RESULTS: Mice underwent pulmonary artery banding to induce RV hypertrophy and RVF. Capillary rarefaction occurred immediately. Although hypoxia-inducible factor-1α expression increased (0.12±0.01 versus 0.22±0.03, P=0.05), VEGF expression decreased (0.61±0.03 versus 0.22±0.05, P=0.01). miR-34a expression was most upregulated in fibroblasts (4-fold), but also in cardiomyocytes and endothelial cells (2-fold). Overexpression of miR-34a in endothelial cells increased cell senescence (10±3% versus 22±2%, P<0.05) by suppressing sirtulin 1 expression, and decreased tube formation by 50% via suppression of hypoxia-inducible factor-1α, VEGF A, VEGF B, and VEGF receptor 2. miR-34a was induced by stretch, transforming growth factor-ß1, adrenergic stimulation, and hypoxia in cardiac fibroblasts and cardiomyocytes. In mice with RVF, locked nucleic acid-antimiR-34a improved RV shortening fraction and survival half-time and restored capillarity and VEGF expression. In children with congenital heart disease-related RVF, RV capillarity was decreased and miR-34a increased 5-fold. CONCLUSIONS: In summary, miR-34a from fibroblasts, cardiomyocytes, and endothelial cells mediates capillary rarefaction by suppressing the hypoxia-inducible factor-1α-VEGF axis in RV hypertrophy/RVF, raising the potential for anti-miR-34a therapeutics in patients with at-risk RVs.

Loss of prolyl hydroxylase 1 and 2 in SM22α-expressing cells prevents Hypoxia-Induced pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a disease characterized by increased vasoconstriction and vascular remodeling. Pulmonary artery smooth muscle cells (PASMCs) highly express the transcription factor hypoxia-inducible factor-1α (HIF-1α), yet the role of PASMC HIF-1α in the development of PAH remains controversial. To study the role of SMC HIF-1α in the pulmonary vascular response to acute and chronic hypoxia, we used a gain-of-function strategy to stabilize HIF-1α in PASMC by generating mice lacking prolyl hydroxylase domain (PHD) 1 and 2 in SM22α-expressing cells. This strategy increased HIF-1α expression and transcriptional activity under conditions of normoxia and hypoxia. Acute hypoxia increased right ventricular systolic pressure (RVSP) in control, but not in SM22α-PHD1/2-/- mice. Chronic hypoxia increased RVSP and vascular remodeling more in control SM22α-PHD1/2+/+ than in SM22α-PHD1/2-/- mice. In vitro studies demonstrated increased contractility and myosin light chain phosphorylation in isolated PHD1/2+/+ compared with PHD1/2-/- PASMC under both normoxic and hypoxic conditions. After chronic hypoxia, there was more p27 and less vascular remodeling in SM22α-PHD1/2-/- compared with SM22α-PHD1/2+/+ mice. Hypoxia increased p27 in PASMC isolated from control patients, but not in cells from patients with idiopathic pulmonary arterial hypertension (IPAH). These findings highlight an SM22α-expressing cell-specific role for HIF-1α in the inhibition of pulmonary vasoconstriction and vascular remodeling. Modulating HIF-1α expression in PASMC may represent a promising preventative and therapeutic strategy for patients with PAH.NEW & NOTEWORTHY In a mouse model wherein hypoxia-inducible factor 1 alpha (HIF-1α) is stabilized in vascular smooth muscle cells, we found that HIF-1α regulates vasoconstriction by limiting phosphorylation of myosin light chain and regulates vascular remodeling through p27 induction. These findings highlight a cell-specific role for HIF-1α in the inhibition of pulmonary vasoconstriction and vascular remodeling.

Prevalence of palliative radiotherapy abstracts presented at the annual scientific meetings of the Canadian Association of Radiation Oncology: 2003-2021.

PURPOSE: Approximately half of all radiotherapy (RT) is delivered with palliative intent. Clinical research in palliative RT aims to manage symptoms, improve quality of life (QoL), evaluate supportive care, and determine optimal dose-fractionation schedules. Our aim was to describe the prevalence of palliative research at the Canadian Association of Radiation Oncology (CARO) Annual Scientific Meeting (ASM) over time and compare this analysis to previously published work which evaluated the years 1992-2002. METHODS: Published abstracts (2003-2021) were independently reviewed by two authors who categorized each as curative-intent; palliative-intent; pertaining to both populations; or neither. Abstracts were considered palliative if they described incurable malignancy and interventions primarily for symptom control or QoL. Type of study, primary, site treated, and symptoms palliated were recorded. Descriptive and summary statistics were calculated including one-way ANOVA test for trend. RESULTS: Three hundred thirty-nine out of 4566 abstracts (7.4%, range 2.4-13.9% per year) were classified as palliative. 7.7% (26/339) described phase I-III trials. The main primary site was the lung (39/339) and the most common metastatic site was the bone (34.2%). QoL, symptom and toxicity outcomes were reported in 31.6% (107/339), 37.8% (128/339) and 17.7% (60/339), respectively. The most common symptom investigated was pain (38/339). The proportion of abstracts classified as curative, palliative or reporting toxicity endpoints demonstrated significant change over time (all p<0.0001). CONCLUSION: While proportion of palliative themed abstracts has increased with time, there remains a significant gap before equivalence with the prevalence of palliative RT in clinical practice is achieved.

Hypoxia-Inducible Factor-1α in SM22α-Expressing Cells Modulates Alveolarization.

Worldwide, the incidence of both preterm births and chronic lung disease of infancy, or bronchopulmonary dysplasia, remains high. Infants with bronchopulmonary dysplasia have larger and fewer alveoli, a lung pathology that can persist into adulthood. Although recent data point to a role for hypoxia-inducible factor-1α (HIF-1α) in mediating pulmonary angiogenesis and alveolarization, the cell-specific role of HIF-1α remains incompletely understood. Thus, we hypothesized that HIF-1α, in a distinct subset of mesenchymal cells, mediates postnatal alveolarization. To test the hypothesis, we generated mice with a cell-specific deletion of HIF-1α by crossing SM22α promoter-driven Cre mice with HIF-1αflox/flox mice (SM22α-HIF-1α-/-), determined SM-22α-expressing cell identity using single-cell RNA sequencing, and interrogated samples from preterm infants. Deletion of HIF-1α in SM22α-expressing cells had no effect on lung structure at day 3 of life. However, at 8 days, there were fewer and larger alveoli, a difference that persisted into adulthood. Microvascular density, elastin organization, and peripheral branching of the lung vasculature were decreased in SM22α-HIF-1α-/- mice, compared with control mice. Single-cell RNA sequencing demonstrated that three mesenchymal cell subtypes express SM22α: myofibroblasts, airway smooth muscle cells, and vascular smooth muscle cells. Pulmonary vascular smooth muscle cells from SM22α-HIF-1α-/- mice had decreased angiopoietin-2 expression and, in coculture experiments, a diminished capacity to promote angiogenesis that was rescued by angiopoietin-2. Angiopoietin-2 expression in tracheal aspirates of preterm infants was inversely correlated with overall mechanical ventilation time, a marker of disease severity. We conclude that SM22α-specific HIF-1α expression drives peripheral angiogenesis and alveolarization in the lung, perhaps by promoting angiopoietin-2 expression.

Optimizing surface mould brachytherapy for treatment of nasal basal cell carcinoma using customized applicators.

PURPOSE: Surface mould brachytherapy (SMBT) is ideal in treating superficial skin cancer over the curved surface of the nasal ala. We describe the process of initiating and optimizing SMBT treatment at our institution including clinical workflow, generation of three dimensional (3D) printed custom applicators, and clinical outcomes. METHODS AND MATERIALS: Planning CT scans were used to acquire images for delineating target volumes. The applicator was designed with customized catheter positioning (3-5mm from target) to cover target volume while sparing dose to organs at risk (OAR) such as adjacent skin and nasal mucosa. Applicators were 3D printed, with transparent resin to aid visualization of underlying skin. Dosimetric parameters evaluated included CTV D90, CTV D0.1cc, and D2cc to OARs. Clinical outcomes assessed were local control, acute and late toxicity (Common Terminology Criteria for Adverse Events v5.0 [CTCAEv5.0]), and cosmesis (Radiation Therapy Oncology Group [RTOG]). RESULTS: Ten patients were treated with SMBT with a median followup of 17.8 months. Dose prescription was 40 Gy in 10 daily fractions. Mean CTV D90 was 38.5 Gy (range 34.7-40.6), mean CTV D0.1cc 49.2 Gy (range 45.6-53.5), which was <140% of the prescription dose in all patients. Treatment was well tolerated, with acceptable Grade 2 acute, Grade 0-1 late skin toxicity, and good-excellent cosmesis for all patients. Two patients experienced local failure, and both underwent surgical salvage. CONCLUSIONS: SMBT was successfully planned and delivered for superficial nasal BCC using 3D printed custom applicators. Excellent target coverage was achieved while minimizing dose to OAR. Toxicity and cosmesis rates were good-excellent.

Data-driven predictions of the time remaining until critical global warming thresholds are reached.

Leveraging artificial neural networks (ANNs) trained on climate model output, we use the spatial pattern of historical temperature observations to predict the time until critical global warming thresholds are reached. Although no observations are used during the training, validation, or testing, the ANNs accurately predict the timing of historical global warming from maps of historical annual temperature. The central estimate for the 1.5 °C global warming threshold is between 2033 and 2035, including a ±1σ range of 2028 to 2039 in the Intermediate (SSP2-4.5) climate forcing scenario, consistent with previous assessments. However, our data-driven approach also suggests a substantial probability of exceeding the 2 °C threshold even in the Low (SSP1-2.6) climate forcing scenario. While there are limitations to our approach, our results suggest a higher likelihood of reaching 2 °C in the Low scenario than indicated in some previous assessments-though the possibility that 2 °C could be avoided is not ruled out. Explainable AI methods reveal that the ANNs focus on particular geographic regions to predict the time until the global threshold is reached. Our framework provides a unique, data-driven approach for quantifying the signal of climate change in historical observations and for constraining the uncertainty in climate model projections. Given the substantial existing evidence of accelerating risks to natural and human systems at 1.5 °C and 2 °C, our results provide further evidence for high-impact climate change over the next three decades.

Internal variability and forcing influence model-satellite differences in the rate of tropical tropospheric warming.

Climate-model simulations exhibit approximately two times more tropical tropospheric warming than satellite observations since 1979. The causes of this difference are not fully understood and are poorly quantified. Here, we apply machine learning to relate the patterns of surface-temperature change to the forced and unforced components of tropical tropospheric warming. This approach allows us to disentangle the forced and unforced change in the model-simulated temperature of the midtroposphere (TMT). In applying the climate-model-trained machine-learning framework to observations, we estimate that external forcing has produced a tropical TMT trend of 0.25 ± 0.08 K⋅decade-1 between 1979 and 2014, but internal variability has offset this warming by 0.07 ± 0.07 K⋅decade-1. Using the Community Earth System Model version 2 (CESM2) large ensemble, we also find that a discontinuity in the variability of prescribed biomass-burning aerosol emissions artificially enhances simulated tropical TMT change by 0.04 K⋅decade-1. The magnitude of this aerosol-forcing bias will vary across climate models, but since the latest generation of climate models all use the same emissions dataset, the bias may systematically enhance climate-model trends over the satellite era. Our results indicate that internal variability and forcing uncertainties largely explain differences in satellite-versus-model warming and are important considerations when evaluating climate models.

Potential for perceived failure of stratospheric aerosol injection deployment.

As anthropogenic activities warm the Earth, the fundamental solution of reducing greenhouse gas emissions remains elusive. Given this mitigation gap, global warming may lead to intolerable climate changes as adaptive capacity is exceeded. Thus, there is emerging interest in solar radiation modification, which is the process of deliberately increasing Earth's albedo to cool the planet. Stratospheric aerosol injection (SAI)-the theoretical deployment of particles in the stratosphere to enhance reflection of incoming solar radiation-is one strategy to slow, pause, or reverse global warming. If SAI is ever pursued, it will likely be for a specific aim, such as affording time to implement mitigation strategies, lessening extremes, or reducing the odds of reaching a biogeophysical tipping point. Using an ensemble climate model experiment that simulates the deployment of SAI in the context of an intermediate greenhouse gas trajectory, we quantified the probability that internal climate variability masks the effectiveness of SAI deployment on regional temperatures. We found that while global temperature was stabilized, substantial land areas continued to experience warming. For example, in the SAI scenario we explored, up to 55% of the global population experienced rising temperatures over the decade following SAI deployment and large areas exhibited high probability of extremely hot years. These conditions could cause SAI to be perceived as a failure. Countries with the largest economies experienced some of the largest probabilities of this perceived failure. The potential for perceived failure could therefore have major implications for policy decisions in the years immediately following SAI deployment.

SM22α cell-specific HIF stabilization mitigates hyperoxia-induced neonatal lung injury.

Though survival rates for preterm infants are improving, the incidence of chronic lung disease of infancy, or bronchopulmonary dysplasia (BPD), remains high. Histologically, BPD is characterized by larger and fewer alveoli. Hypoxia-inducible factors (HIFs) may be protective in the context of hyperoxia-induced lung injury, but the cell-specific effects of HIF expression in neonatal lung injury remain unknown. Thus, we sought to determine whether HIF stabilization in SM22α-expressing cells can limit hyperoxia-induced neonatal lung injury. We generated SM22α-specific HIF-1α-stabilized mice (SM22α-PHD1/2-/- mice) by cross-breeding SM22α-promotor-driven Cre recombinase mice with prolyl hydroxylase PHD1flox/flox and PHD2flox/flox mice. Neonatal mice were randomized to 21% O2 (normoxia) or 80% O2 (hyperoxia) exposure for 14 days. For the hyperoxia recovery studies, neonatal mice were recovered from normoxia for an additional 10 wk. SM22α-specific HIF-1α stabilization mitigated hyperoxia-induced lung injury and preserved microvessel density compared with control mice for both neonates and adults. In SM22α-PHD1/2-/- mice, pulmonary artery endothelial cells (PAECs) were more proliferative and pulmonary arteries expressed more collagen IV compared with control mice, even under hyperoxic conditions. Angiopoietin-2 (Ang2) mRNA expression in pulmonary artery smooth muscle cells (PASMC) was greater in SM22α-PHD1/2-/- compared with control mice in both normoxia and hyperoxia. Pulmonary endothelial cells (PECs) cocultured with PASMC isolated from SM22α-PHD1/2-/- mice formed more tubes and branches with greater tube length compared with PEC cocultured with PASMC isolated from SM22α-PHD1/2+/+ mice. Addition of Ang2 recombinant protein further augmented tube formation for both PHD1/2+/+ and PHD1/2-/- PASMC. Cell-specific deletion of PHD1 and 2 selectively increases HIF-1α expression in SM22α-expressing cells and protects neonatal lung development despite prolonged hyperoxia exposure. HIF stabilization in SM22α-expressing cells preserved endothelial cell proliferation, microvascular density, increased angiopoietin-2 expression, and lung structure, suggesting a role for cell-specific HIF-1α stabilization to prevent neonatal lung injury.

Stereotactic body radiotherapy for head and neck skin cancer.

AIM: To report outcomes of Stereotactic Body Radiotherapy (SBRT) for head and neck skin cancer (HNSC) patients treated at a high-volume center. MATERIALS: A retrospective review of HNSC SBRT patients from 2012 to 2019 was conducted. Kaplan-Meier method was used to estimate local control (LC), locoregional control (LRC) outside of SBRT field, overall survival (OS), progression-free survival (PFS) and late toxicity (LT). Univariate and multivariate analyses were performed. Grade 3-4 acute and late toxicities were reported by the Common Terminology Criteria for Adverse Events v5.0. RESULTS: One hundred and six medically unfit HNSC patients (112 lesions) were included. Median follow-up was 8 months. Median patient age at diagnosis was 86 years (range: 56-102 years). The majority of patients had advanced disease (overall stage III-IV [n = 90, 85%]) with median gross tumor volumes (GTV) of 31 cm3 (range: 17-56 cm3). Treated sites were: primary (n = 51), nodal (n = 47) or primary plus nodal (n = 8). SBRT doses ranged from 32-50 Gy delivered twice weekly in 4-6 fractions to the gross tumor volume (GTV). One and 2-year LC rates were 78% (69-88) and 67% (53-82), respectively. One-year LRC outside of SBRT field, OS, PFS and LT rates were 72% (62-84), 53% (43-65), 52% (40-62), and 7% (2-17), respectively. Thirty-three patients (31%) developed acute grade ≥ 3 treatment-related toxicity, most commonly dermatitis (n = 31). Nine patients (8%) experienced late grade ≥ 3 toxicity, including 7 grade 3 fibrosis, 1 grade 3 bone radionecrosis and 1 grade 4 skin ulceration. No treatment-related deaths (grade 5) were observed. CONCLUSION: SBRT provides durable disease control with acceptable toxicity for medically unfit high-risk HNSC patients unable to undergo standard of care curative treatment approaches.

Additive manufacturing (3D printing) in superficial brachytherapy.

The aim of this work is to provide an overview of the current state of additive manufacturing (AM), commonly known as 3D printing, within superficial brachytherapy (BT). Several comprehensive database searches were performed to find publications linked to AM in superficial BT. Twenty-eight core publications were found, which can be grouped under general categories of clinical cases, physical and dosimetric evaluations, proof-of-concept cases, design process assessments, and economic feasibility studies. Each study demonstrated a success regarding AM implementation and collectively, they provided benefits over traditional applicator fabrication techniques. Publications of AM in superficial BT have increased significantly in the last 5 years. This is likely due to associated efficiency and consistency benefits; though, more evidences are needed to determine the true extent of these benefits.

Substantial lymphovascular space invasion predicts worse outcomes in early-stage endometrioid endometrial cancer.

INTRODUCTION: Substantial as opposed to focal or no lymphovascular space invasion (LVSI) is proposed as an independent adverse prognostic factor in patients with early-stage endometrioid endometrial cancer (EEC). We reviewed outcomes of patients treated with adjuvant vaginal brachytherapy (VB) alone in a single institution, stratified by LVSI extent. METHODS AND MATERIALS: Retrospective review identified Stage I-II EEC patients receiving VB alone from 2010 to 2017. Extent of LVSI was reported as none, focal, or substantial. Kaplan-Meier estimates and Log-Rank test were used to determine significance between variables. Cox proportional hazards model was used for multivariate analyses. RESULTS: In total, 325 patients were identified with a median follow-up of 35 (23-48) months. LVSI was found in 112 patients with extent reported in 78, 45 (58%) had focal, and 33 (42%) substantial LVSI. Estimated disease-free survival for those with substantial LVSI was 73 (57-94)%, focal LVSI 89 (79-100)%, and no LVSI 94 (90-98)% at 48 months (p = 0.012). On multivariate analyses substantial LVSI was the only risk factor predictive of pelvic [HR substantial vs no: 7.2 (1.0-51.6); p = 0.048] and distant failure [HR substantial vs no: 4.4 (1.2-16.3); p = 0.027]. Both high-grade disease [HR 3 vs 1: 5.5 (1.2-25.6); p = 0.031] and extent of LVSI [HR substantial vs no: 4.4 (1.7-11.4); p = 0.002] predicted for worse disease-free survival. DISCUSSION: Substantial LVSI was the strongest adverse prognostic factor for pelvic and distant failure in this cohort of EEC patients receiving adjuvant VB alone, suggesting this subset may benefit from additional adjuvant therapy. This study underscores the importance of quantifying LVSI extent in EEC.

Radiation for below the knee skin cancers: a single institution experience.

Background: Historically, radiation to skin cancers for the lower legs has been avoided due to the perceived increased risk of radiation toxicity (poor wound healing, radiation necrosis). However, there is a paucity of published data regarding this perceived risk.Purpose: The objective was to review the risk of poor wound healing/radiation necrosis occurring post radiation and to determine rates of complete response (CR), partial response (PR), and progressive disease after radiation therapyMaterials and methods: A retrospective review of patients treated with radiation for skin cancer below the knee was undertaken from January 1, 2013 to May 31, 2018.Results: A total of 25 patients with 39 below the knee skin sites were treated with radiation. Mean follow-up time was 19 months (range 3 months-7.2 years). Crude CR, PR and progression rates for the treated lesions were 65%, 19%, and 16% respectively. Four out of 23 (17%) patients developed Grade 3 skin toxicity. There were no grades 4 or 5 toxicities.Conclusions: For patients not eligible for surgery, radiation therapy is an option with a moderate chance of complete response (65%) and a 17% risk of poor wound healing/radiation necrosis.

Multiple bone metastases: what the palliative care specialist should know about the potential, limitations and practical aspects of radiation therapy.

Bone metastases represent a significant health care problem in the cancer population. The most common symptom for bone metastases is pain. Bone metastases may also cause pathologic fracture, spinal cord compression, cauda equina compression and serum calcium disorders. This review article summarizes the epidemiology, diagnostic modalities, role for radiation, and future directions as it pertains to bone metastases. Radiotherapy is an effective and standard modality for the treatment of painful complicated and uncomplicated bony metastases. Further strategies are needed to optimize pain relief, quality of life and survival in the bone metastases cancer population.

Past Variance and Future Projections of the Environmental Conditions Driving Western U.S. Summertime Wildfire Burn Area.

Increases in vapor pressure deficit (VPD) have been hypothesized as the primary driver of future fire changes. The Coupled Model Intercomparison Project Phase 5 (CMIP5) models agree that western U.S. surface temperatures and associated dryness of air as defined by the VPD will increase in the 21st century for Representative Concentration Pathways (RCPs) 4.5 and 8.5. However, we find that averaged over seasonal and regional scales, other environmental variables demonstrated to be relevant to flammability, moisture abundances, and aridity-such as precipitation, evaporation, relative humidity, root zone soil moisture, and wind speed-can be used to explain observed variance in wildfire burn area as well or better than VPD. However, the magnitude and sign of the change of these variables in the 21st century are less certain than the predicted changes in VPD. Our work demonstrates that when objectively selecting environmental variables to maximize predictive skill of linear regressions (minimize square error on unseen data) VPD is not always selected and when it is not, the magnitude of future increases in burn area becomes less certain. Hence, this work shows that future burn area predictions are sensitive to what environmental predictors are chosen to drive burn area.

Radiotherapy practices in postoperative endometrial cancer: A survey of the ABS membership.

PURPOSE: This survey aimed to document the current practice patterns of postoperative radiotherapy (RT), including vaginal vault brachytherapy (VVB) and external beam radiotherapy (EBRT), in the management of patients with endometrial cancer. METHODS AND MATERIALS: A 30-item, multiple choice survey querying RT prescribing practices and planning techniques was distributed electronically to American Brachytherapy Society members in December 2018. RESULTS: Seventy-five surveys from 62 centers were completed. Eighty-nine percent of respondents practiced within the USA or Canada. Most (79%) respondents indicated a preference for recommending adjuvant VVB alone in FIGO Stage IB, Grade 2 margin and lymphovascular space invasion (LVSI) negative disease. For FIGO Stage IB, Grade 3, LVSI-positive disease, most respondents preferred incorporating EBRT either alone (33%) or with VVB (28%). For IIIC1, margin positive disease, VVB in addition to EBRT was most commonly recommended (75%). When planning adjuvant EBRT, 49% utilized CT simulation with both bladder full and empty. Internal target volume was utilized by 53%. Volumetric modulated arc therapy (53%) or intensity-modulated radiotherapy (19%) were commonly used planning techniques. The most common dose prescription was 45 Gy in 25 fractions (57%). When treating with VVB, 49% determined applicator size at the time of brachytherapy. Sixty-four percent planned treatments based on CT imaging with the applicator in situ and 33% repeated CT imaging before each subsequent fraction. The most common prescription was 21 Gy in three fractions prescribed to 0.5 cm depth (43%). CONCLUSIONS: This study identified variability in treatment recommendations and in both EBRT and VVB simulation and planning processes in postoperative endometrial cancer.

Vaginal brachytherapy alone for patients with Stage II endometrial cancer with inner half cervical stromal invasion.

PURPOSE: The purpose of this study was to review outcomes of women with Stage II endometrial carcinoma with inner half cervical stromal invasion treated with adjuvant vaginal brachytherapy (VB) alone. METHODS AND MATERIALS: A single-institution retrospective chart review identified consecutive patients with Stage II endometrial cancer and inner half cervical stromal invasion treated with VB alone from 2011 to 2015. Patients who received chemotherapy or external beam radiotherapy were excluded. Patient and disease characteristics were collected. Association between variables and outcomes were assessed using Fisher's exact or Wilcoxon rank sum test. RESULTS: Fifty-seven patients were identified over 5 years with a median followup of 46.8 months. Carcinoma was endometrioid Grade 1 (43.9%), 2 (36.8%), 3 (5.3%), or serous (14.0%). Depth of myometrial invasion was inner half in 75.4%. Lymphovascular invasion was seen in 28.1%, and lymph node assessment was performed in 43.9% of patients. The median depth of cervical stromal invasion was 1.25 mm (n = 48 patients). The median percentage of the cervical stromal wall invaded by tumor (obtained in 40 patients) was 16.7%. Seven (12.3%) patients recurred at a median of 16.9 months. Five-year estimates of progression-free survival and overall survival were 81.5% and 78.5%, respectively. The only factor associated with recurrence, progression-free survival or overall survival on bivariate analysis was high-grade (Grade 3 or serous) disease (p = 0.031). CONCLUSIONS: VB alone can be considered for Stage II patients with inner half cervical stromal invasion and Grade 1-2 disease. Systemic therapy may be required for patients with Grade 3 and serous histology as 75% (3/4) of these recurrences were outside the pelvis.