Gender Representation Among Academic US Radiation Oncology Department Chairs: Who are They?

Purpose: Women are underrepresented in academic radiation oncology (RO), particularly in leadership positions. In this study, we sought to better understand the characteristics of individuals who currently serve as academic RO chairpersons at institutions with an associated Accreditation Council for Graduate Medical Education-accredited RO residency training program. Methods and Materials: We created a database of academic RO chairpersons in the United States by using publicly available sources, including residency training program websites, hospital/institutional websites, Doximity, LinkedIn, the American Society for Radiation Oncology (ASTRO) website, the American College of Radiation Oncology website, and the National Plan and Provider Enumeration System National Provider Identifier Registry. We used the χ2 Goodness of Fit test, Mann-Whitney U test, and Fisher exact test via R version 4.1.1 to evaluate for statistical significance among categorical variables, medians, and proportions, respectively. Results: We identified 85 of the 90 chairpersons (94.4%) currently serving at institutions with an Accreditation Council for Graduate Medical Education-accredited RO residency training program, 5 of whom hold interim positions and were thus excluded from further analyses. Of the remaining 80 chairpersons, 9 (11.3%) are women, and 71 (88.8%) are men (P < .01). Seventy-six chairpersons (95.0%) are full professors, and 19 (23.8%) hold dual MD PhD degrees. Thirty-two chairpersons (40.0%) hold an official leadership role in a cancer center affiliated with their current institution (43.7% of men vs 11.1% of women; P = .08). Seventy-three chairpersons (91.3%) secured their current positions a median of 16 years (range, 6-33 years) after completing RO residency. Thirty-five chairpersons (43.8%) were promoted to chair from positions within their current institutions (40.8% of men vs 66.7% of women; P = .17). The majority of chairpersons are ASTRO Fellows (62.5%); notably fewer are ASTRO (5.0%) or American College of Radiation Oncology (2.5%) Gold Medalists. Eight RO residency programs trained more than half of current chairpersons. Conclusion: Significantly more men than women currently serve as RO chairpersons. Future interventions that promote the recruitment, retention, and promotion of talented women in academic RO should be considered.

Comparison of prone and supine positioning for breast cancer radiotherapy using REQUITE data: dosimetry, acute and two years physician and patient-reported outcomes.

OBJECTIVE: Most patients receive whole breast radiotherapy in a supine position. However, two randomised trials showed lower acute toxicity in prone position. Furthermore, in most patients, prone positioning reduced doses to the organs at risk. To confirm these findings, we compared toxicity outcomes, photographic assessment, and dosimetry between both positions using REQUITE data. METHODS: REQUITE is an international multi-centre prospective observational study that recruited 2069 breast cancer patients receiving radiotherapy. Data on toxicity, health-related quality of life (HRQoL), and dosimetry were collected, as well as a photographic assessment. A matched case control analysis compared patients treated prone (n = 268) versus supine (n = 493). Exact matching was performed for the use of intensity-modulated radiotherapy, boost, lymph node irradiation, chemotherapy and fractionation, and the nearest neighbour for breast volume. Primary endpoints were dermatitis at the end of radiotherapy, and atrophy and cosmetic outcome by photographic assessment at two years. RESULTS: At the last treatment fraction, there was no significant difference in dermatitis (p = .28) or any HRQoL domain, but prone positioning increased the risk of breast oedema (p < .001). At 2 years, patients treated in prone position had less atrophy (p = .01), and higher body image (p < .001), and social functioning (p < .001) scores. The photographic assessment showed no difference in cosmesis at 2 years (p = .22). In prone position, mean heart dose (MHD) was significantly lower for left-sided patients (1.29 Gy vs 2.10 Gy, p < .001) and ipsilateral mean lung dose (MLD) was significantly lower for all patients (2.77 Gy vs 5.89 Gy, p < .001). CONCLUSIONS: Prone radiotherapy showed lower MLD and MHD compared to supine position, although the risk of developing breast oedema during radiotherapy was higher. At 2 years the photographic assessment showed no difference in the cosmetic outcome, but less atrophy was seen in prone-treated patients and this seems to have a positive influence on the HRQoL domain of body image.

Genome-wide association study of treatment-related toxicity two years following radiotherapy for breast cancer.

BACKGROUND AND PURPOSE: Up to a quarter of breast cancer patients treated by surgery and radiotherapy experience clinically significant toxicity. If patients at high risk of adverse effects could be identified at diagnosis, their treatment could be tailored accordingly. This study was designed to identify common single nucleotide polymorphisms (SNPs) associated with toxicity two years following whole breast radiotherapy. MATERIALS AND METHODS: A genome-wide association study (GWAS) was performed in 1,640 breast cancer patients with complete SNP, clinical, treatment and toxicity data, recruited across 18 European and US centres into the prospective REQUITE cohort study. Toxicity data (CTCAE v4.0) were collected at baseline, end of radiotherapy, and annual follow-up. A total of 7,097,340 SNPs were tested for association with the residuals of toxicity endpoints, adjusted for clinical, treatment co-variates and population substructure. RESULTS: Quantile-quantile plots showed more associations with toxicity above the p < 5 × 10-5 level than expected by chance. Eight SNPs reached genome-wide significance. Nipple retraction grade ≥ 2 was associated with the rs188287402 variant (p = 2.80 × 10-8), breast oedema grade ≥ 2 with rs12657177 (p = 1.12 × 10-10), rs75912034 (p = 1.12 × 10-10), rs145328458 (p = 1.06 × 10-9) and rs61966612 (p = 1.23 × 10-9), induration grade ≥ 2 with rs77311050 (p = 2.54 × 10-8) and rs34063419 (p = 1.21 × 10-8), and arm lymphoedema grade ≥ 1 with rs643644 (p = 3.54 × 10-8). Heritability estimates across significant endpoints ranged from 25% to 39%. Our study did not replicate previously reported SNPs associated with breast radiation toxicity at the pre-specified significance level. CONCLUSIONS: This GWAS for long-term breast radiation toxicity provides further evidence for significant association of common SNPs with distinct toxicity endpoints.

Gender Differences in the Research Productivity of Radiation Oncology Resident Graduates in the United States: 2015 to 2019.

Purpose: It is well-documented that gender disparities exist in academic radiation oncology departments. The purpose of this study was to analyze gender differences in research productivity during residency among recent graduates of radiation oncology training programs in the United States (US). Methods and Materials: We used several publicly available sources to create a database of US radiation oncology residents who graduated between 2015 and 2019. We systematically collected gender information from the National Plan and Provider Enumeration System National Provider Identifier Registry and Medicare claims registry. Postresidency employment information was collected using several publicly available sources. PubMed was queried to identify first-author publications of residents. A secondary analysis of metadata including impact factor, number of citations, modified Hirsch index (h index), and type of publication was performed. A multivariable linear regression was performed to evaluate the effect of gender on research productivity during residency. Results: There were 910 total graduates identified during this period and who were entered into this database, of whom all had available gender information. Female trainees comprised 29.0% (n = 264) of RO residents and had fewer first-author publications and citations, had lower mean modified h index, and were published in journals with lower impact factors. On multivariable linear regression analysis, female gender was independently associated with decreased total number of publications (P = .005), mean number of citations (P < .001), and modified h index (P = .001) when controlling for residency size and advanced (PhD or master's) degrees. Conclusions: In the US, female RO trainees had lower research productivity, which was not explained by advanced degrees or residency size. A significant gender gap in trainee research productivity persists, which has known implications in terms of academic achievement, promotions, and career trajectory. Future interventions to improve resident research productivity and mentorship are warranted.

Imaging-defined necrosis after treatment with single-fraction stereotactic radiosurgery and immune checkpoint inhibitors and its potential association with improved outcomes in patients with brain metastases: an international multicenter study of 697 patients.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS) are commonly utilized in the management of brain metastases. Treatment-related imaging changes (TRICs) are a frequently observed clinical manifestation and are commonly classified as imaging-defined radiation necrosis. However, these findings are not well characterized and may predict a response to SRS and ICIs. The objective of this study was to investigate predictors of TRICs and their impact on patient survival. METHODS: This retrospective multicenter cohort study was conducted through the International Radiosurgery Research Foundation. Member institutions submitted de-identified clinical and dosimetric data for patients with non-small cell lung cancer (NSCLC), melanoma, and renal cell carcinoma (RCC) brain metastases that had been treated with SRS and ICIs. Data were collected from March 2020 to February 2021. Univariable and multivariable Cox and logistic regression analyses were performed. The Kaplan-Meier method was used to evaluate overall survival (OS). The diagnosis-specific graded prognostic assessment was used to guide variable selection. TRICs were determined on the basis of MRI, PET/CT, or MR spectroscopy, and consensus by local clinical providers was required. RESULTS: The analysis included 697 patients with 4536 brain metastases across 11 international institutions in 4 countries. The median follow-up after SRS was 13.6 months. The median age was 66 years (IQR 58-73 years), 54.1% of patients were male, and 57.3%, 36.3%, and 6.4% of tumors were NSCLC, melanoma, and RCC, respectively. All patients had undergone single-fraction radiosurgery to a median margin dose of 20 Gy (IQR 18-20 Gy). TRICs were observed in 9.8% of patients. The median OS for all patients was 24.5 months. On univariable analysis, Karnofsky Performance Status (KPS; HR 0.98, p < 0.001), TRICs (HR 0.67, p = 0.03), female sex (HR 0.67, p < 0.001), and prior resection (HR 0.60, p = 0.03) were associated with improved OS. On multivariable analysis, KPS (HR 0.98, p < 0.001) and TRICs (HR 0.66, p = 0.03) were associated with improved OS. A brain volume receiving ≥ 12 Gy of radiation (V12Gy) ≥ 10 cm3 (OR 2.78, p < 0.001), prior whole-brain radiation therapy (OR 3.46, p = 0.006), and RCC histology (OR 3.10, p = 0.01) were associated with an increased probability of developing TRICs. The median OS rates in patients with and without TRICs were 29.0 and 23.1 months, respectively (p = 0.03, log-rank test). CONCLUSIONS: TRICs following ICI and SRS were associated with a median OS benefit of approximately 6 months in this retrospective multicenter study. Further prospective study and additional stratification are needed to validate these findings and further elucidate the role and etiology of this common clinical scenario.

A Review of the Role of Stereotactic Radiosurgery and Immunotherapy in the Management of Primary Central Nervous System Tumors.

Stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICIs) are widely used in the management of brain metastases. These therapies are commonly administered concurrently; as SRS may enhance anti-tumor immunity and responsiveness to ICIs. However, the use of ICIs with and without SRS in the management of primary brain tumors remains a controversial topic. Meningiomas are the most common nonmalignant and extra-parenchymal brain tumor, which often respond well to surgery and radiotherapy. However, higher grade meningiomas tend to be resistant to these treatments, and the use of chemotherapy and targeted agents in this setting have yielded disappointing results. Thus, there is heightened interest in the utilization of ICIs. Glioblastoma is the most common malignant primary intraparenchymal brain tumor. It is associated with a grim prognosis with a median overall survival of approximately 20 months, despite optimal therapy. While SRS in the adjuvant setting, and ICI in the recurrent setting, have failed to demonstrate a survival benefit, SRS in the preoperative setting has the potential to enhance anti-tumor immunity and responsiveness to ICIs. Thus, these treatments represent an attractive option to add to the armamentarium of meningioma and glioblastoma management. In this review, we provide a detailed overview of the evidence supporting the use of ICIs and SRS in each of these settings.

Concurrent Administration of Immune Checkpoint Inhibitors and Stereotactic Radiosurgery Is Well-Tolerated in Patients With Melanoma Brain Metastases: An International Multicenter Study of 203 Patients.

BACKGROUND: Melanoma brain metastases are commonly treated with stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICIs). However, the toxicity of these 2 treatments is largely unknown when administered concurrently. OBJECTIVE: To evaluate the risk of radiation necrosis (RN) with concurrent and nonconcurrent SRS and ICIs. METHODS: The guidelines from the Strengthening the Reporting of Observational Studies in Epidemiology checklist were used. Inverse probability of treatment weighting, univariable and multivariable logistic regression, and the Kaplan-Meier method was utilized. RESULTS: There were 203 patients with 1388 brain metastases across 11 international institutions in 4 countries with a median follow-up of 15.6 months. The rates of symptomatic RN were 9.4% and 8.2% in the concurrent and nonconcurrent groups, respectively ( P =.766). On multivariable logistic regression, V12 ≥ 10 cm 3 (odds ratio [OR]: 2.76; P =.006) and presence of BRAF mutation (OR: 2.20; P =.040) were associated with an increased risk of developing symptomatic RN; the use of concurrent over nonconcurrent therapy was not associated with an increased risk (OR: 1.06; P =.877). There were 20 grade 3 toxic events reported, and no grade 4 events reported. One patient experienced a grade 5 intracranial hemorrhage. The median overall survival was 36.1 and 19.8 months for the concurrent and nonconcurrent groups (log-rank P =.051), respectively. CONCLUSION: Concurrent administration of ICIs and SRS are not associated with an increased risk of RN. Tumors harboring BRAF mutation, or perhaps prior exposure to targeted agents, may increase this risk. Radiosurgical optimization to maintain V12 < 10 cm 3 is a potential strategy to reduce the risk of RN.

Trauma-Informed Radiation Therapy: Implementation and Evaluation of a Sensitive Practice Tool for Female Patients Undergoing Radiotherapy for Breast Cancer.

PURPOSE: For childhood sexual abuse survivors, cancer care can be retraumatizing because of perceived similarities to the original sexual violence. The authors' group designed and implemented a sensitive practice tool (SPT) and evaluated the feasibility of the tool in female patients receiving breast radiation. METHODS: The SPT was offered as a "universal precaution" to patients with breast cancer as part of standard clinical care. Patients were given the SPT, which included an instructional video about radiotherapy and a survey about triggers and preferences. The survey results were provided to radiation therapists and used to personalize patients' care. A retrospective chart review and quality improvement survey of therapists were performed. RESULTS: Of 739 eligible patients, 493 (66.7%) completed the SPT from November 2013 to June 2019. Among respondents, 281 (57.0%) reported potential triggers, 395 (80.1%) reported distress management preferences, and 59 (12.0%) requested psychosocial referrals. Mean patient satisfaction was high, and a majority of patients were likely to recommend the SPT to other patients (85.3%). Among radiation therapists (n = 13), 100% reported that the SPT made it easier to customize or individualize patient care. Trauma disclosure was not significantly associated with increased frequency of trigger endorsement (P = .07) but was associated with increased endorsement of distress management preferences (P = .02) and psychosocial referral requests (P < .001). CONCLUSIONS: The reported experience with the SPT in the breast radiotherapy setting demonstrated that potential triggers and distress management preferences among patients are common and that patient satisfaction with the SPT is high, yielding clinically meaningful and actionable sensitive practice information.

The Cognitive Effects of Radiotherapy for Brain Metastases.

Brain metastases are the most common intracranial neoplasm and are seen in upwards of 10-30% of patients with cancer. For decades, whole brain radiation therapy (WBRT) was the mainstay of treatment in these patients. While WBRT is associated with excellent rates of intracranial tumor control, studies have demonstrated a lack of survival benefit, and WBRT is associated with higher rates of cognitive deterioration and detrimental effects on quality of life. In recent years, strategies to mitigate this risk, such as the incorporation of memantine and hippocampal avoidance have been employed with improved results. Furthermore, stereotactic radiosurgery (SRS) has emerged as an appealing treatment option over the last decade in the management of brain metastases and is associated with superior cognitive preservation and quality of life when compared to WBRT. This review article evaluates the pathogenesis and impact of cranial irradiation on cognition in patients with brain metastases, as well as current and future risk mitigation techniques.

Development and Optimization of a Machine-Learning Prediction Model for Acute Desquamation After Breast Radiation Therapy in the Multicenter REQUITE Cohort.

Purpose: Some patients with breast cancer treated by surgery and radiation therapy experience clinically significant toxicity, which may adversely affect cosmesis and quality of life. There is a paucity of validated clinical prediction models for radiation toxicity. We used machine learning (ML) algorithms to develop and optimise a clinical prediction model for acute breast desquamation after whole breast external beam radiation therapy in the prospective multicenter REQUITE cohort study. Methods and Materials: Using demographic and treatment-related features (m = 122) from patients (n = 2058) at 26 centers, we trained 8 ML algorithms with 10-fold cross-validation in a 50:50 random-split data set with class stratification to predict acute breast desquamation. Based on performance in the validation data set, the logistic model tree, random forest, and naïve Bayes models were taken forward to cost-sensitive learning optimisation. Results: One hundred and ninety-two patients experienced acute desquamation. Resampling and cost-sensitive learning optimisation facilitated an improvement in classification performance. Based on maximising sensitivity (true positives), the "hero" model was the cost-sensitive random forest algorithm with a false-negative: false-positive misclassification penalty of 90:1 containing m = 114 predictive features. Model sensitivity and specificity were 0.77 and 0.66, respectively, with an area under the curve of 0.77 in the validation cohort. Conclusions: ML algorithms with resampling and cost-sensitive learning generated clinically valid prediction models for acute desquamation using patient demographic and treatment features. Further external validation and inclusion of genomic markers in ML prediction models are worthwhile, to identify patients at increased risk of toxicity who may benefit from supportive intervention or even a change in treatment plan.

Modern radiation techniques in early stage breast cancer for the breast radiologist.

Partial breast irradiation (PBI) and ultra-hypofractionated whole breast irradiation (uWBI) are contemporary alternatives to conventional and standard hypofractionated whole breast irradiation (WBI), which shorten treatment from 3 to 6 weeks to 1-2 weeks for select patients. PBI and accelerated PBI (APBI) can be delivered with external beam radiation (3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT)), intraoperative radiation (IORT), or brachytherapy. These new radiation techniques offer the advantage of convenience and lower cost, which ultimately improves access to care. Globally, the COVID 19 pandemic has accelerated APBI/PBI and ultra-hypofractionated regimens into routine practice for carefully selected patients. Recent long-term data from randomized controlled trials (RCTs) have demonstrated these techniques are safe and effective in suitable patients demonstrating equivalent or improved local recurrence, acute/late toxicity, and cosmesis. PBI and APBI should be limited to low risk unifocal invasive ductal carcinoma and ductal carcinoma in situ with tumor size < 2 cm, clear margins (≥2 mm), ER+, and negative nodes. Based on the results from UK Fast-Forward and UK FAST ultra-hypofractionated breast radiation can be safely employed for early stage node negative patients, but is not yet considered an international standard of care. In this review, authors will appraise recent data for these shorter course radiation treatment regimens, as well as, considerations for breast radiologists including surveillance imaging and radiographic findings.

Multidisciplinary management of metastatic spine disease: initial symptom-directed management.

In the past 2 decades, a deeper understanding of the cancer molecular signature has resulted in longer longevity of cancer patients, hence a greater population, who potentially can develop metastatic disease. Spine metastases (SM) occur in up to 70% of cancer patients. Familiarizing ourselves with the key aspects of initial symptom-directed management is important to provide SM patients with the best patient-specific options. We will review key components of initial symptoms assessment such as pain, neurological symptoms, and spine stability. Radiographic evaluation of SM and its role in management will be reviewed. Nonsurgical treatment options are also presented and discussed, including percutaneous procedures, radiation, radiosurgery, and spine stereotactic body radiotherapy. The efforts of a multidisciplinary team will continue to ensure the best patient care as the landscape of cancer is constantly changing.

Experiencing the Surge: Report From a Large New York Radiation Oncology Department During the COVID-19 Pandemic.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic is affecting all aspects of life and changing the practice of medicine. Multiple recommendations exist on how radiation oncology practices should deal with this crisis, but little information is available on what actually happens when the COVID-19 surge arrives. New York City experienced the first surge of COVID-19 in the United States and is now the epicenter of the global pandemic. This study reviews how COVID-19 has affected aspects of medicine, nursing, radiation therapy, and administration in a hospital system in New York. METHODS AND MATERIALS: A retrospective review was conducted of the department of radiation oncology in a single health system in New York from March 1, 2020, to April 1, 2020. Collaboration was obtained from physicians, nurses, radiation therapy staff, and administration to recall their policies and effect on specific duties. A timeline was reconstructed to chronicle significant events. Numbers were obtained for patients on treatment, treatment breaks, and COVID-19 infections among staff and patients. RESULTS: The COVID-19 surge has had a tremendous effect on the health system, such as cessation of all of surgeries, including oncologic surgery, and transfer of all inpatient oncology services to makeshift outpatient facilities. Radiation oncology has made aggressive efforts to reduce the number of patients in treatment to protect patients and staff and to reallocate staff and space for more acute clinical needs. Patients on-beam were reduced by 27% from 172 to 125 by April 1. Almost all visits were changed to telemedicine within 2 weeks. Infection rates and quarantine were quite low among staff and patients. The majority of residents were deployed into COVID-19 clinical settings. CONCLUSIONS: Although we "planned for the worst," our health system was able to make necessary changes to still function at a reduced capacity. Our experience will give other departments a concrete experience to help them make their own policies and manage expectations.

Communicating hydrocephalus after radiosurgery for vestibular schwannomas: does technique matter? A systematic review and meta-analysis.

BACKGROUND: Communicating hydrocephalus (cHCP) after radiosurgery (RS) for vestibular schwannomas (VS) has been reported. Many hypothetical mechanisms for this pathology have been proposed without consensus. The aim of this study is to determine if the platform used to treat the disease, Gamma Knife (GK) versus linear accelerator (LINAC)-based RS, makes a difference in outcome. METHODS: We conducted a meta-analysis of databases PubMed and Cochrane to identify all articles for the period January 2000-August 2018 with the following inclusion criteria: (1) VS treated with single fraction SRS (2) > 10 patients (3) original reports only (4) hydrocephalus reported as complication (5) human study. RESULTS: A total of 7039 and 988 VS patients reported in 35 and 10 papers were treated with GK or LINAC RS, respectively. Demographic baseline characteristics not reported in aggregate did not differ between the two groups. The incidence of cHCP was 3% [95% CI 2-4] and 2% [95% CI 1-3] for GK and LINAC RS patients, respectively. Surgical CSF diversion was performed in 88% and 68% of patients evaluated for cHPC in the GK and LINAC group, respectively. Follow-up range was 30-150 and 29-92 months for GK and LINAC, respectively. CONCLUSIONS: The incidence of cHCP following RS for VS is very low in both GK and LINAC treated patients, albeit not identical. The higher reported surgical intervention rate for VS patients treated with GK RS might be multi-factorial, including longer follow-up in the GK group.

von Willebrand Factor Gene Expression in Primary Lower Grade Glioma: Mutually Co-Occurring Mutations in von Willebrand Factor, ATRX, and TP53.

BACKGROUND: Venous thromboembolism is a common complication in patients with glioma. The clotting factor von Willebrand factor (VWF) is a highly adhesive procoagulant molecule that mediates platelet adhesion to endothelial and subendothelial surfaces. In the current analysis, we examined The Cancer Genome Atlas (TCGA) data to assess the VWF gene in patients with lower grade gliomas. METHODS: For newly diagnosed gliomas, we evaluated the association between VWF and overall survival in the Genomic Data Commons TCGA Lower Grade Glioma (LGG) dataset in TCGA. Simple statistics were calculated to identify patterns of mutual exclusivity or co-occurrence of VWF mutations. For each pair of query genes an odds ratio was calculated that indicates the likelihood that the mutations in the two genes are mutually exclusive or co-occurrent across the selected cases. To determine whether the identified relationship was significant for a gene pair, Fisher's exact test was performed. RESULTS: Lower grade gliomas with less VWF gene expression had significantly better survival than those with more VWF gene expression (hazard ratio 0.64, 95% confidence interval 0.44 to 0.92, p=0.015 log rank test). When we analyzed the data with Cox regression, VWF expression had a significant effect on survival (p=0.02) that was unrelated to the effect of IDH1 expression (p=0.062), TP53 expression (p=0.135), independent of ATRX expression (p=0.021) and histology (astrocytoma versus oligoastrocytoma and oligodendroglioma, p=0.002). VWF mutations significantly co-occur with mutations in TP53 and ATRX (p<0.001). CONCLUSION: The deleterious prognostic effect of VWF expression and its co-occurrent mutations with TP53 and ATRX in lower grade gliomas are not surprising, given VWF's role in other cancers. Therefore, VWF gene expression may be a clinically important risk marker in lower grade glioma.

Increased RNA Expression of von Willebrand Factor Gene Is Associated With Infiltrating Lobular Breast Cancer and Normal PAM50 Subtype.

BACKGROUND: Infiltrating lobular carcinoma (ILC) is the second most common histologicaI subtype of breast cancer, accounting for 10% of all cases. ILC has a characteristic genomic profile. ILC shows a high frequency of cadherin 1 (CDH1) mutations, along with loss of phosphatase and tensin homolog (PTEN), activation of alpha serine/threonine kinase (AKT), and mutations in T-box transcription factor (TBX3) and forkhead box protein A1 (FOXA1). We suspected that another gene, von Willebrand factor (VWF), might also be part of the profile, since coagulation tests reveal significant differences in patients with breast cancer. MATERIALS AND METHODS: For newly-diagnosed breast cancer, the association between VWF and histology in the GDC Breast Cancer dataset in The Cancer Genome Atlas (TCGA) was evaluated. The following were used to access and analyze the data: Genomic Data Commons Data Portal (https://portal.gdc.cancer.gov/); Xena browser (https://xenabrowser.net); cBioportal (http://cbioportal.org); Oncomine (https://oncomine.org); and Prediction Analysis of Microarray 50 (PAM50). RESULTS: Patients with ILC had higher VWF RNA expression than patients with infiltrating ductal carcinoma and other histology. The difference of expression was present to the same degree in both pre-menopausal and post-menopausal patients. Nine alterations in VWF and PTEN were significantly co-occurrent. Considering all histologies in 843 samples, Tukey's honest significant difference post hoc test showed that VWF RNA expression of the normal subtype was significantly greater than that of the other subtypes (p<0.001). CONCLUSION: Our finding of significantly higher VWF RNA expression in the PAM50 normal (non-basal-like) breast cancer subtype suggests that VWF protein measurement might complement or corroborate PAM50 results. VWF and PAM50 results both suggesting a low risk of recurrence might make the decision whether to give chemotherapy easier, especially if VWF protein were an independent predictor.

Biological and psychosocial predictors of anxiety worsening in the postpartum period: A longitudinal study.

BACKGROUND: As many as 20% of women will experience an anxiety disorder during the perinatal period. Women with pre-existing anxiety disorders are at increased risk of worsening during this time, yet little is known about its predictors. STUDY AIM: To investigate the psychosocial and biological risk factors for anxiety worsening in the postpartum in women with pre-existing anxiety disorders. METHODS: Thirty-five (n = 35) pregnant women with pre-existing DSM-5 anxiety disorders were enrolled in this prospective study investigating the psychosocial (e.g., childhood trauma, intolerance of uncertainty, depression) and biological risk factors (e.g. C-reactive protein, interleukin-6, tumor necrosis factor-α) for anxiety worsening in the postpartum period. Anxiety worsening was defined as an increase of ≥50% or greater on Hamilton Anxiety Rating Scale scores from the third trimester of pregnancy (32.94 ± 3.35 weeks) to six weeks postpartum. RESULTS: Intolerance of uncertainty, depressive symptom severity, and obsessive-compulsive disorder symptoms present in pregnancy were significant predictors of anxiety worsening in the postpartum. LIMITATIONS: Sample heterogeneity and limited sample size may affect study generalizability. CONCLUSIONS: To our knowledge, this is the first longitudinal study to investigate psychosocial and biological risk factors for anxiety worsening in the postpartum in women with pre-existing anxiety disorders. Continued research investigating these risk factors is needed to elucidate whether they differ from women experiencing new-onset anxiety disorders in the perinatal period, and those in non-puerperal groups. Identifying these risk factors can guide the development of screening measures for early and accurate symptom detection. This can lead to the implementation of appropriate interventions aimed at decreasing the risk of perinatal anxiety worsening.

Analysis of Local Control and Pain Control After Spine Stereotactic Radiosurgery Reveals Inferior Outcomes for Hepatocellular Carcinoma Compared With Other Radioresistant Histologies.

PURPOSE: This study aimed to evaluate the efficacy of stereotactic radiosurgery (SRS) for spinal metastases from hepatocellular carcinoma (HCC) compared with other radioresistant histologies (renal cell carcinoma [RCC], melanoma, and sarcoma) in terms of local control (LC) and pain control. METHODS AND MATERIALS: We performed a retrospective review of patients treated with SRS to the spine for metastatic HCC, RCC, melanoma, and sarcoma between January 2007 and May 2014. Radiographic assessments of LC, overall survival, and patient-reported pain control were analyzed as univariable analyses and with various patient- and treatment-related parameters as multivariable analyses (MVA). RESULTS: Of the 96 patients treated with SRS, 41 patients had radioresistant histologies, including 18 HCC, 1 mixed HCC and cholangiocarcinoma, 15 RCC, 6 melanoma, and 1 leiomyosarcoma. Extraosseous disease was present in 63% of patients (74% in HCC; 55% in non-HCC; P = not significant). Spinal cord compression was present in 29% of patients (32% in HCC; 27% in non-HCC; P = not significant), and 24% of patients had decompressive surgery before SRS (26% in HCC; 23% in non-HCC; P = not significant). With a median follow-up time of 8.7 months, the actuarial 3-, 6-, and 12-month LC rates were 71%, 61%, 41%, respectively, for HCC, and 94%, 94%, and 85%, respectively, for non-HCC. The median time to local failure was 3 months for HCC and 11 months for non-HCC. On MVA, there was a strong trend toward inferior LC with HCC (P = .059). Of the 28 patients with pretreatment pain, pain relief was achieved in 93% of patients, but the 2 patients who did not experience pain relief both had HCC. The actuarial 3-, 6-, and 12-month pain control rates were 68%, 51%, 17%, respectively, for HCC, and 100%, 89%, and 89%, respectively, for non-HCC (P = .023), and remained significant on MVA (P = .034). CONCLUSIONS: Compared with other radioresistant histologies, HCC has inferior LC and pain relief after SRS. Whether HCC may benefit from further dose escalation or combined treatment with new therapies is an area of future research.