Patient treatment and outcome after breast cancer orbital and periorbital metastases: a comprehensive case series including analysis of lobular versus ductal tumor histology.

BACKGROUND: Breast cancer is the most common malignancy to spread to the orbit and periorbit, and the invasive lobular carcinoma (ILC) histologic subtype of breast cancer has been reported to form these ophthalmic metastases (OM) more frequently than invasive ductal carcinomas (IDC). We herein report our single academic institution experience with breast cancer OM with respect to anatomical presentation, histology (lobular vs. ductal), treatment, and survival. METHODS: We employed the natural language processing platform, TIES (Text Information Extraction System), to search 2.3 million de-identified patient pathology and radiology records at our institution in order to identify patients with OM secondary to breast cancer. We then compared the resultant cohort, the "OM cohort," to two other representative metastatic breast cancer patient (MBC) databases from our institution. Histological analysis of selected patients was performed. RESULTS: Our TIES search and manual refinement ultimately identified 28 patients who were diagnosed with breast cancer between 1995 and 2016 that subsequently developed OM. Median age at diagnosis was 54 (range 28-77) years of age. ER, PR, and HER2 status from the 28 patients with OM did not differ from other patients with MBC from our institution. The relative proportion of patients with ILC was significantly higher in the OM cohort (32.1%) than in other MBC patients in our institution (11.3%, p = 0.007). Median time to first OM in the OM cohort was 46.7 months, and OM were the second most frequent first metastases after bony metastases. After diagnosis of the first distant metastasis of any kind, median survival of patients with ILC (21.4 months) was significantly shorter than that of patients with IDC (55.3 months, p = 0.03). Nine patients developed bilateral OM. We observed a significant co-occurrence of OM and central nervous system metastases (p = 0.0053). The histological analysis revealed an interesting case in which the primary tumor was of a mixed ILC/IDC subtype, while only ILC was present in the OM. CONCLUSIONS: OM from breast cancer are illustrative of the difference in metastatic behavior of ILC versus IDC and should be considered when treating patients with ILC, especially in those with complaints of visual acuity changes.

Overexpression of Flap Endonuclease 1 Correlates with Enhanced Proliferation and Poor Prognosis of Non-Small-Cell Lung Cancer.

Flap endonuclease 1 (FEN1) plays a crucial role in both DNA replication and damage repair. In this study, FEN1 expression and its clinical-pathologic significance in non-small-cell lung cancer (NSCLC) was investigated. Quantitative RT-PCR and immunohistochemistry analysis identified that both FEN1 mRNA and protein were highly overexpressed in about 36% of 136 cancer tissues compared to adjacent tissues, in which FEN1 was generally undetectable. Notably, patients with FEN1-overexpressed cancers were prone to have poor differentiation and poor prognosis. A strong positive correlation between the levels of FEN1 and Ki-67 staining was identified in these NSCLC tissues (r = 0.485), suggesting overexpressed FEN1 conferred a proliferative advantage to NSCLC. Furthermore, knockdown of FEN1 resulted in G1/S or G2/M phase cell cycle arrest and suppressed in vitro cellular proliferation in NSCLC cancer cells. Consistently, a selective FEN1 inhibitor was shown to effectively inhibit cellular proliferation of NSCLC cells in a dose-dependent manner. Additionally, knockdown of FEN1 significantly attenuated homologous DNA repair efficiency and enhanced cytotoxic effects of cisplatin in NSCLC cells. Taken together, these findings have indicated that overexpressed FEN1 represents a prognostic biomarker and potential therapeutic target for NSCLC treatment, which warrants further study.

Are the Affordable Care Act Restrictions Warranted? A Contemporary Statewide Analysis of Physician-Owned Hospitals.

BACKGROUND: The Affordable Care Act placed a moratorium on physician-owned hospital (POH) expansion. Concern exists that POHs increase costs and target healthier patients. However, limited historical data support these claims and are not weighed against contemporary measures of quality and patient satisfaction. The purpose of this study was to investigate the quality, costs, and efficiency across hospital types. METHODS: One hundred forty-five hospitals in a single state were analyzed: 8 POHs; 16 proprietary hospitals (PHs); and 121 general, full-service acute care hospitals (ACHs). Multiyear data from the Centers for Medicare and Medicaid Services Medicare Cost Report and the statewide Health Care Cost Containment Council were analyzed. RESULTS: ACHs had a higher percentage of Medicare patients as a share of net patient revenue, with similar Medicare volume. POHs garnered significantly higher patient satisfaction: mean Hospital Consumer Assessment of Healthcare Providers and Systems summary rating was 4.86 (vs PHs: 2.88, ACHs: 3.10; P = .002). POHs had higher average total episode spending ($22,799 vs PHs: $18,284, ACHs: $18,856), with only $1435 of total spending on post-acute care (vs PHs: $3867, ACHs: $3378). Medicare spending per beneficiary and Medicare spending per beneficiary performance rates were similar across all hospital types, as were complication and readmission rates related to hip or knee surgery. CONCLUSION: POHs had better patient satisfaction, with higher total costs compared to PHs and ACHs. A focus on efficiency, patient satisfaction, and ratio of inpatient-to-post-acute care spending should be weighted carefully in policy decisions that might impact access to quality health care.

High Dose Intravenous Vitamin C Treatment for Zika Fever.

The Zika Fever is a viral disease caused by a single-stranded RNA virus from the Flavivirus genus, Flaviviridae family, from the Spondweni group. Its transmission occurs through mosquito vectors, principally Aedes Aegypti. The most common symptoms of Zika are fever, rash, joint pain, and conjunctivitis (red eyes). Other common symptoms include muscle pain and headache. As of now, no vaccine exists for the virus and no official treatment has been developed aside from standard procedures of the use of acetaminophen (paracetamol) and non-steroidal anti-inflammatory drugs. This is a case report of a 54 year-old Hispanic female who arrived at the clinic with symptomatology congruent with the Zika fever. The patient was treated with high doses of intravenous vitamin C over three days. The symptoms resolved after the infusions without any side effects at day four. Recovery from this viral infection takes normally around two weeks. Based on the positive outcome in this case, we propose that intravenous vitamin C should be studied further as a potential treatment for acute viral infections.

Difficult Diagnosis between B Cell Lymphoma and Classical Hodgkin's Lymphoma.

Although primary mediastinal large B-cell lymphoma and classic Hodgkin lymphoma of nodular sclerosis type are distinct disease, they share several clinical characteristics and biologic features. However, there are mediastinal lymphomas that not fit in either category. These types of lymphomas are recognized as mediastinal gray zone lymphomas. Gray zone lymphomas are lymphatic tumors that cannot be assigned to a defined lymphoma entity due to morphological, clinical, or genetic reasons. In this report, we present a case of a 22 year-old-Hispanic-female diagnosed with B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Hodgkin lymphoma.

Investigating how implementation intentions improve non-focal prospective memory tasks.

Implementation intentions are a self-regulatory strategy broadly studied in the area of social cognition that can improve realization of one's goals and improve performance on prospective memory tasks. Three experiments, using a non-focal task for which the prospective memory targets were specified at the time of intention formation, investigated whether (and how) implementation intentions can improve non-focal prospective memory performance. An improvement in prospective memory performance was accompanied by an increase in the allocation of conscious resources to the prospective memory task, but not by an increase in perceived importance of the prospective memory task. The third experiment also investigated the effects of implementation intentions on recall of the appropriate action and found that accurate action recall was improved by implementation intentions. Finally, the effect of implementation intention instructions on cognitive processes that underlie non-focal prospective memory performance was investigated using a multinomial model.

High Dose Intraveneous Vitamin C and Chikungunya Fever: A Case Report.

The Chikungunya (CHIKV) fever is a viral disease produced by a single-stranded RNA Alphavirus from the Togaviridae genus. Its transmission occurs only through mosquito vectors, principally Aedes aegypti. It requires a human-mosquito-human transmission cycle. It is associated with severe arthritis/arthralgias, myalgias, high fever, headache, and maculopapular rash. Joint ache appears to be symmetrical. The virus has an incubation period of 2 to 7 days, where the high fever is typically presented. It is followed by arthralgias and myalgias, and rashes, which last for 3 to 5 days. However, the arthralgias can persist for months after the infection, which can contribute to severe arthritis. As of now, no vaccine exists for the virus and no official treatment has been developed aside from standard procedures of the use of acetaminophen (paracetamol), and non-steroidal anti-inflammatory drugs. This is a case report of a 54-year old Hispanic individual that reported left shoulder pain, left knee pain and fever. The symptoms started on a Saturday in September 2014 in middle of the night. The patient was treated with high doses of intravenous vitamin C over two days. The symptoms resolved after the infusions without any side effects. Based on the positive outcome in this case, we propose that intravenous vitamin C should be studied further as a potential treatment for acute viral infections.

Did the COVID-19 pandemic have an effect on oral cancer staging? A single-centre retrospective observational study.

Introduction This study aims to assess if the COVID-19 pandemic impacted upon oral cancer staging in a single centre in the UK.Materials and methods Data were collected from the head and neck cancer database of a teaching hospital in London. Oral cancer diagnosis and staging in the peak period of the pandemic (March 2020-2021) were assessed against the one-year period (March 2019-2020) before the pandemic.Results In total, 25 cases of oral cancer were diagnosed in the pre-COVID-19 group compared to 26 in the COVID-19 cohort. Referrals from dentists accounted for 30% of cases of confirmed oral cancer in the COVID-19 class in comparison to 48% the year prior. Higher rates of overall TNM (tumour, lymph node, metastasis) staging at level 4a and above were observed in the COVID-19 cohort at 68% in comparison to 48% the year before.Conclusion Marginal non-statistically significant differences were noted of worsening stages of oral cancer presentations in the first year of the COVID-19 pandemic in this unit. Long-term studies on the outcomes of those diagnosed with oral cancer during the pandemic at a regional and national level will facilitate greater analysis on the impact the pandemic had on this cohort.

Clinical Features and Therapeutic Outcomes Comparing Primary Mediastinal Large B-cell Lymphoma to Mediastinal Hodgkin Disease.

Currently, there is limited data available comparing Primary Mediastinal Large B-cell Lymphoma (PMBL) and mediastinal Hodgkin disease, nodular sclerosis type (HDNS). This is a retrospective cohort study that compares the clinical features, histology through immunohistochemistry (IHC) and treatment outcomes of 19 cases of PMBL and 39 cases of HDNS diagnosed over 13 years at a single institution in San Juan, PR. Superior Vena Cava syndrome (SVCS) and elevated Lactate Dehydrogenase (LDH) levels were more frequently seen in the PMBL cohort. At the median follow-up visit, of 74 months, no significant difference was seen in overall survival or progression free survival between PMBL and HDNS. Almost all of the relapses in the PMBL group occurred within 12 months of diagnosis. Our data suggests that PMBL and HDNS differ in their clinical presentation and have a favorable prognosis.

The role of glycerol-water mixtures in the stability of FKBP12-rapalog-FRB complexes.

The thermodynamic and biophysical implications of the introduction of a co-solvent during protein-ligand binding remain elusive. Using ternary complexes of 12-kDa FK506 binding protein (FKBP12), FKBP-rapamycin binding (FRB) domain of the mammalian/mechanistic target of rapamycin (mTOR) kinase, and rapamycin analogs (rapalogs) in glycerol-water mixtures, the influence of solvent composition on ligand binding dynamics was explored. The pharmaceutical potential of rapalogs and the utility of glycerol as a co-solvent in drug delivery applications were critical in deciding the system to be studied. Consolidation of existing studies on rapamycin modification was first performed to strategically design a new rapalog called T1. The results from 100-ns dual-boost Gaussian accelerated molecular dynamics simulations showed that protein stability was induced in the presence of glycerol. Reweighting of the trajectories revealed that the glycerol-rich solvent system lowers the energy barrier in the conformational space of the protein while also preserving native contacts between the ligand and the residues in the binding site. Calculated binding free energies using MM/GBSA also showed that electrostatic energy and polar contribution of solvation energy are heavily influenced by the changes in solvation. Glycerol molecules are preferentially excluded through electrostatic interactions from the solvation shell which induce complex stability as seen in existing experiments. Hence, using glycerol as a co-solvent in rapamycin delivery has a significant role in maintaining stability. In addition, compound T1 is a potential mTORC1-selective inhibitor with strong affinity for the FKBP12-FRB complex. This study aims to provide insights on the design of new rapalogs, and the applicability of glycerol as co-solvent for FKBP12-rapalog-FRB complexes.

Can we reduce dose to ureters as avoidance organs for MRI based brachytherapy for cervical cancer? A dosimetric feasibility study.

BACKGROUND AND PURPOSE: Ureteral stenosis (US) is an underreported complication of brachytherapy (BT) for cervical cancer (CC), with limited data on toxicity risk reduction. A previous study demonstrated ureter EQD2 D0.1cc > 77 Gy correlated with US development. We sought to assess feasibility of this constraint while maintaining similar HR-CTV coverage. MATERIALS AND METHODS: Patients with locally advanced CC treated with EBRT plus HDR MRI-based brachytherapy boost without hydronephrosis at diagnosis and with ureter dose EQD2 D0.1cc > 77 Gy were included. Replan was attempted to achieve HR-CTV D90 ≥ 80-85 Gy and ureter dose reduction. Ureter distance from lateral margin of HR-CTV and tandem was recorded. t-test was performed to compare ureteral dose and HR-CTV D90. RESULTS: Of 25 patients were identified. Hundred percent received 45 Gy in 25 fractions to the pelvis ± paraaortic lymph nodes and 80% receiving median additional parametrial dose of 5.4 Gy. Replan meeting ureteral dose of ≤77 Gy was feasible in 18 of 25 patients, with a reduction in median ureter D0.1cc from 82.3 to 76.8 Gy (p < 0.001). Median HR-CTV D90 was similar (84.7 vs. 85.0 Gy). Replan achieved D0.1cc ≤77 Gy in 56% of patients who experienced US. All unilateral US cases occurred in the ureter closest to HR-CTV. CONCLUSIONS: Optimization to reduce ureter dose to ≤77 Gy is feasible when ureters are visible and contoured. Ureters may be considered as potential OAR during MRI-based brachytherapy treatment. Reduced ring to tandem total reference air kerma (TRAK) ratio may provide an additional metric by which to lower US risk.

Treatment of intermediate-risk prostate cancer with Cs-131: Long-term results from a single institution.

PURPOSE: To evaluate our institutional outcomes utilizing Cs-131 prostate brachytherapy (PB) for the intermediate-risk (IR) group of prostate cancer patients. METHODS AND MATERIALS: We reviewed a prospectively collected database of men treated with Cs-131 PB between 2006 and 2019. Patients with less than 24-months follow-up were excluded. Patients were classified as IR if they had one of the following factors: Gleason Score 7, prostate specific antigen >10 but <20 ng/mL, or T2b-c on clinical exam. We defined unfavorable-IR (UIR) as having either Grade Group 3, >1 IR factors, or ≥50% positive core biopsies. The Kaplan-Meier method was used to estimate actuarial event-time probabilities for biochemical freedom from disease (BFD). RESULTS: A total of 335 patients with a median follow-up of 70.1 months (IQR 48.3-106.3 months) were identified. Androgen deprivation therapy (ADT) was used in 7.2% of patients. Favorable-IR (FIR) patients were commonly treated with PB alone (91.8%). FIR patients who underwent PB alone had a 5-year BFD of 98.1%. UIR patients were commonly treated with external beam radiotherapy plus PB (61.2%). These patients had 5-year BFD of 91.1%. The 5-year BFD for UIR patients treated without ADT was 90.9%, whereas it was 95.0% among UIR patients treated with ADT (log-rank p = 0.83). CONCLUSIONS: FIR patients have excellent outcomes when treated with PB alone. External beam radiotherapy plus PB is a reasonable treatment approach for UIR patients. Future studies may elucidate which IR patients would benefit from treatment intensification.

Utility of Prophylactic Cranial Irradiation for Extensive-Stage Small-Cell Lung Cancer in the MRI Screening Era.

BACKGROUND: Conflicting data exists regarding the benefit of prophylactic cranial irradiation (PCI) in patients with extensive-stage small-cell lung cancer (ES-SCLC). We sought to retrospectively review outcomes of patients within our network with ES-SCLC treated with and without PCI between 2009 and 2020. METHODS: Endpoints assessed using the Kaplan-Meier estimator were overall survival (OS), freedom from death with uncontrolled intracranial disease (UI-DFS), brain metastasis-free survival (BMFS), and symptomatic BMFS (SBMFS). Log-rank test was performed for univariate comparison of outcomes, with Cox regression performed for univariate and multivariable analysis of OS and UI-DFS. RESULTS: Some 250 patients were determined to be eligible for PCI based on any response to upfront chemotherapy, with 46 patients excluded owing to lack of negative staging brain magnetic resonance imaging (MRI). Brain MRI was performed both at diagnosis and near completion of chemotherapy in 108 patients, with brain metastases identified near completion of chemotherapy in 17 patients (15.7%), excluding them from further analysis. Median OS in remaining eligible 187 patients was 9.0 months, with 2-year Kaplan-Meier estimate of OS of 21.9%. PCI was associated with improved UI-DFS, BMFS, and SBMFS. However, PCI was not associated with improved OS in the entire cohort or the propensity matched cohort. CONCLUSION: Our study suggests screening with MRI following chemotherapy is important because of the identification of unsuspected brain metastases in nearly 16% of patients with response to chemotherapy. PCI is associated with reduction in brain metastases, without a demonstrable impact on OS in the era of MRI screening.

An Emergency Department Clinical Algorithm to Increase Early Palliative Care Consultation: Pilot Project.

Introduction: The emergency department (ED) is a primary entry point of hospitals but does not have a system to identify and consult palliative care (PC) early in patients who meet criteria. Objectives: To determine the measurable effects of an ED PC consultation on patients who meet criteria, hypothesizing that ED PC consultation would lead to decreased average length of stay (ALOS), average direct cost per patient, decreased number of surgeries, and radiological tests performed per patient. Materials and Methods: A physician-led data-driven evidence-based algorithm was designed and piloted with implementation in two hospitals during January-March 2019 in Orlando, FL. A retrospective review of health record data was completed, comparing patients receiving PC consultation ordered in the ED versus those ordered after admission. Results: ED patients (n = 662) met PC criteria. PC consultation was ordered in ED for 80 (12.1%) cases. The following outcomes were lower for patients who received ED PC consultation than those who did not: ALOS by 6.4 days (6.74 vs. 13.14 days; p < 0.001), in-hospital mortality (12.5% vs. 19.1%; p = 0.11), surgery (11% vs. 37%; p < 0.01), radiological tests per patient (4.01 vs. 10.57; p < 0.001), and average direct cost per patient ($7,193 vs. $22,354). However, 30-day hospital revisit rates were relatively higher in those who did receive ED PC consultation than those who did not (20% vs. 13% p = 0.15). Conclusions: In this pilot project, PC patients can be identified in the ED with an algorithm that leads to earlier consultation and improved patient outcomes. Larger research trials are needed to replicate this strategy and results.

Long term outcomes with linear accelerator stereotactic radiosurgery for treatment of jugulotympanic paragangliomas.

BACKGROUND: Data supporting linear accelerator (linac) stereotactic radiosurgery (SRS) for jugulotympanic paragangliomas (JTPs) come from small series with minimal follow-up. Herein, we report a large series of JTPs with extended follow-up after frameless linac-based SRS. METHODS: JTPs treated with linac-based SRS from 2002 to 2019 with 1+ follow-up image were reviewed for treatment failure (radiographic or clinical progression, or persistent symptoms after SRS requiring intervention) and late toxicities (CTCAE v5.0). RESULTS: Forty JTPs were identified; 30 were treated with a multifraction regimen. Median clinical and radiographic follow-up was 79.7 (interquartile range [IQR] 31.7-156.9) and 54.4 months (IQR 17.9-105.1), respectively, with a median 4.5 follow-up scans (IQR 2-9). Seven-year progression-free survival (PFS) was 97.0% (95% confidence interval 91.1%-100.0%). PFS was similar between single- and multifraction regimens (log rank P = .99). Toxicity was seen in 7.7% (no grade III). CONCLUSIONS: With extended clinical and radiographic follow-up, frameless linac-based SRS provides excellent local control with mild toxicity <8%.

Treatment selection and survival outcomes in Early-Stage peripheral T-Cell lymphomas: does anaplastic lymphoma kinase mutation impact the benefit of consolidative radiotherapy?

The role of consolidative radiotherapy (RT) is less substantiated in uncommon peripheral T-cell lymphomas (PTCLs). Anaplastic lymphoma kinase (ALK) mutation sub-categorizes PTCLs, with ALK (+) having a distinctly favorable prognosis. We aimed to use the National Cancer Database to examine the potential role of RT in PTCLs and if ALK mutation can be used to predict the benefit of consolidative RT after multi-agent chemotherapy (combined modality therapy). We identified 3670 stage I-II PTCL patients treated with multi-agent chemotherapy alone or combined modality therapy (CMT) between 1998-2012. After adjusting for immortal-time and indication bias, CMT was associated with better OS than multi-agent chemotherapy alone for ALK (-) patients (HR 0.69, 95% CI 0.52-0.92, p = .01); no significant difference was noted for ALK (+) (HR 1.03, 95% CI 0.75-1.41, p = .85). CMT is associated with improved OS for ALK (-) PTCLs; while no such benefit was seen for the ALK (+) subgroup.

Ureteral stenosis after 3D MRI-based brachytherapy for cervical cancer - Have we identified all the risk factors?

BACKGROUND AND PURPOSE: Ureteral stenosis (US) is a known complication from image-guided brachytherapy (IGBT); however, no dosimetric parameter has been associated with ureteral toxicity. We aimed to report the rate of late grade ≥3 US after MRI-based IGBT, and to identify clinical factors and dosimetric parameters predictive for US. MATERIALS AND METHODS: A retrospective review was performed on all cervical cancer patients treated with MRI-based IGBT between 2007 and 2017. Late grade ≥3 US was recorded according to CTCAE 4.03. The minimum dose to the maximally irradiated 0.1 cm3 of ureter (D0.1cm3) was extracted from dose-volume histograms. Binary logistic regression was performed to identify predictors of late grade ≥3 US. RESULTS: 242 patients with a median follow-up of 35.8 months (IQR, 19.2-60.8) were identified. Late grade ≥3 US occurred in 18 patients, and the actuarial 3-year rate was 7.3% (95% CI 3.3-11.3). After excluding patients with pre-existing hydronephrosis, late grade ≥3 US occurred in 11 patients with an actuarial 3-year rate of 4.4% (95% CI 1.7-7.1). Ureters with D0.1cm3 ≥77 Gy had a 28.6% incidence of late grade ≥3 US compared to 7.5% in those with D0.1cm3 <77 Gy (OR 2.39; 95% CI 1.23-4.65; p = 0.01). The incidence of late grade ≥3 US was 33.3%, and 40.0% for ureters receiving ≥85 and ≥90 Gy, to D0.1cm3, respectively. CONCLUSION: After MRI-based IGBT, there is an estimated 4.4% risk of developing late grade ≥3 US among patients without pre-existing hydronephrosis. Ureteral dose ≥77 Gy to D0.1cm3 correlates with development of late grade ≥3 US.

Intraprostatic calcification and biochemical recurrence in men treated with cesium-131 prostate brachytherapy.

PURPOSE: Baseline intraprostatic calcification (IC) has been shown to be associated with a higher rate of biochemical recurrence (BCR) in men treated with iodine-125 prostate brachytherapy (PB). We evaluated this association in a cohort of men treated with cesium-131 PB. METHODS AND MATERIALS: We retrospectively reviewed the charts of all low- and intermediate-risk prostate cancer patients treated with cesium-131 PB +/- external beam radiotherapy (EBRT) at our institution from 2/2011 to 7/2018. Patients with < 24 months of follow up or those who received androgen deprivation therapy were excluded. Baseline IC status (defined as one or more ICs ≥ 5 mm) was determined on post-PB CT scans. Cox analysis was used to assess predictors of BCR and Kaplan-Meier survival curves were calculated. RESULTS: Two hundred and sixteen low- and intermediate-risk prostate cancer patients treated with cesium-131 PB +/- EBRT were included. Median follow up was 56.9 months (range 24.1-111.4). Overall, 76 (35.2%) patients had baseline IC and 140 (64.8%) did not. Baseline disease characteristics did not differ significantly between groups. On univariate Cox analysis, only risk group (p = 0.047) and initial PSA (p = 0.016) were significant predictors of BCR, whereas baseline IC was not (p = 0.11). The 5-year BCR-free survival in patients with versus without baseline IC was 97.7% versus 93.8% (p = 0.405), respectively. CONCLUSIONS: In a cohort of low- and intermediate-risk prostate cancer patients treated with cesium-131 PB, the rate of BCR in men with baseline IC was low and baseline IC was not associated with a higher risk of BCR.

Do air gaps with image-guided vaginal cuff brachytherapy impact failure rates in patients with high-intermediate risk FIGO Stage I endometrial cancer?

PURPOSE: The aim of this study was to assess the impact of air gaps at the cylinder surface on the rate of vaginal cuff failure (VCF) after image-guided adjuvant vaginal cuff brachytherapy (VCBT) in the treatment of high-intermediate risk (HIR) FIGO (Fédération Internationale de Gynécologie et d'Obstétrique (International Federation of Gynecology and Obstetrics)) Stage I endometrial cancer. METHODS AND MATERIALS: A retrospective review of patients treated with image-guided VCBT from 2009 to 2016 for HIR FIGO Stage I endometrial cancer was performed. Air gaps present at the applicator surface on the first postinsertion CT were contoured. Vaginal cuff failure-free survival (VCFFS) was measured from the first fraction of VCBT to VCF. RESULTS: A total of 234 patients were identified. Air gaps were present on the first postinsertion CT scan in 82% of patients. The median number of air gaps was 2 (interquartile range [IQR] 1-3), median depth of the largest air gap was 2.7 mm (IQR 2.1-3.4 mm), and the median cumulative volume of air gaps was less than 0.1 cm3 (range < 0.1-0.7 cm3). At a median followup of 56 months (IQR 41-69), 12 patients (5%) experienced VCF, of which 4 had isolated VCF and 8 had synchronous pelvic or distant failure. Five-year VCFFS and isolated VCFFS were 96% (95% confidence interval 93-98%) and 98% (95% confidence interval 96-100%), respectively. On univariate analysis, no factors, including the presence, number, maximum depth, or cumulative volume of air gaps, were predictive for VCFFS. CONCLUSIONS: In this population, VCFFS remained high despite most patients having air gaps present on postinsertion CT scan.

Patterns of Failure After Adjuvant Stereotactic Body Radiation Therapy for Pancreatic Cancer With Close or Positive Margins.

PURPOSE: There is no consensus on treatment volumes for adjuvant stereotactic body radiation therapy (SBRT) for pancreatic cancer. Herein, we report patterns of failure after pancreatic SBRT for close/positive margins, which may inform target volume design. METHODS AND MATERIALS: An institutional review board-approved retrospective review of patients with pancreatic adenocarcinoma treated with adjuvant SBRT for close/positive margins from 2009 to 2018 was conducted. Patterns of failure were defined as local (LF) within the tumor bed, regional (RF) within lymph nodes or anastomoses, or distant (DF). The cumulative incidence of locoregional failure was calculated using the cumulative incidence function accounting for the competing risk of death. LFs were mapped to the planning target volume (PTV) and classified as in-field (completely within the PTV), marginal (partially within the PTV), or out-of-field (completely outside the PTV). The location of LFs was compared with the Radiation Therapy Oncology Group 0848 contouring atlas to determine whether standard postoperative radiation therapy volumes would have included the LF. RESULTS: Seventy-six patients were treated with adjuvant SBRT for close (51.3%) or positive (48.7%) margins. Most (81.6%) received 36 Gy in 3 fractions, with a median PTV volume of 17.8 cc (interquartile range, 12.1-25.6). With a median follow-up of 17.0 months (interquartile range, 7.3-28.4), crude rates of first isolated LF, isolated RF, and DF +/- LF or RF were 9.2%, 6.6%, and 56.6%, respectively. Two-year cumulative incidences of LF, RF, locoregional failure, and DF were 34.9%, 30.8%, 49.2%, and 60.4%, respectively. Of 28 reviewable LFs, 21.4% were in-field while the remainder were completely outside (60.7%) or partially outside (17.9%) the PTV. Most LFs (92.9%) would have been encompassed by the Radiation Therapy Oncology Group consensus target volumes. CONCLUSIONS: After adjuvant pancreatic SBRT for close/positive margins, the majority of LFs were outside the PTV but within contemporary target volumes for conventional radiation therapy.