Psychosocial well-being during the COVID-19 pandemic among women with and without breast cancer.

OBJECTIVE: Treatment delays in combination with general social distancing practices to reduce transmission may have negative impacts on the mental health of women with breast cancer who may need more social and emotional support. We sought to elucidate the psychosocial effects of the COVID-19 pandemic among women with and without breast cancer in New York City. METHODS: We conducted a prospective cohort study among women aged 18+ across the spectrum of breast health care at New York Presbyterian (NYP)-Weill Cornell, NYP-Brooklyn Methodist Hospital and NYP-Queens. Women were contacted between June and October 2021 to assess their self-reported depression, stress, and anxiety during the COVID-19 pandemic. We compared women who were recently diagnosed, those with a history of breast cancer, and women without cancer whose other health visits were delayed during the pandemic. RESULTS: There were 85 women who completed the survey. Breast cancer survivors (42%) were the least likely to report a delay in care due to COVID compared to breast cancer patients who were recently diagnosed (67%) and women without cancer (67%). Compared to women without cancer and breast cancer survivors, women recently diagnosed with breast cancer reported higher levels of anxiety and depression with a statistically significant difference in perceived stress. CONCLUSIONS: Our findings highlight the need to identify and risk-stratify patients facing a new breast cancer diagnosis in and around the COVID-19 pandemic who may benefit from additional resources to mitigate the adverse impacts of the pandemic and a breast cancer diagnosis on psychosocial health.

Mutant p53 and the response to chemotherapy and radiation.

In addition to playing roles in the genesis and progression of cancer, mutant p53 also appears to play a significant role in the response to cancer therapy. In response to chemotherapy and radiation, two mainstays of cancer treatment, most cancer cells harboring p53 mutations show a reduced sensitivity compared to cells lacking p53 or those with wild type p53. However, there are also many instances where mutant p53 has shown no effect or enhances cellular sensitivity to chemotherapy and radiation. Similar to the in vitro cellular studies, the majority of clinical studies show a correlation between the presence of mutant p53 in patient tumors and adverse outcomes following treatment with chemotherapy agents or radiation in comparison to tumors with wild-type p53. However, it still remains unclear whether the presence of mutant p53 in tumors can serve as a reliable prognostic factor and aid in treatment planning. Thus, as genomic analysis of patient tumors becomes more cost effective, the role of mutant p53 in tumor responses from cancer therapy ultimately needs to be addressed. This chapter will discuss current mechanisms of how p53 mutations affect cellular responses to chemotherapy and radiation and discuss patient outcomes based on p53 status.

Routine histopathologic characteristics can predict oncotype DX(TM) recurrence score in subsets of breast cancer patients.

This study assessed whether routine pathologic parameters could predict Oncotype DX(TM) recurrence score (RS) in 72 breast cancers diagnosed from 2008-2012. Comparing patients with low RS (0-17) vs. intermediate RS (18-30) vs. high RS (>30), the mean Nottingham score increased (5.5 vs. 6.3 vs. 7.2, respectively, p = .001) and the mean PR Allred score decreased (6.7 vs. 4.9 vs. 3.3, respectively, p = .001). A high RS was least likely for low-grade tumors (0% had high RS, p = .005), and strong PR positivity (9% had high RS, p = .017). A low RS was least likely for cancers that were both high grade and PR weak/negative.

The Significance of Lymph Node Ratio and Total Lymph Nodes Examined in Determining the Indications of Adjuvant Radiation in pN2 Non-small Cell Lung Cancer.

INTRODUCTION/BACKGROUND: Past studies have shown mixed results of postoperative radiation (PORT) for pN2 NSCLC patients. We hypothesize that PORT can improve overall survival (OS) in pN2 NSCLC patients with high lymph node ratio (LNR). MATERIALS/METHODS: The National Cancer Database was queried for non-metastatic pN2 NSCLC patients with R0 surgery and adjuvant chemotherapy from 2004 to 2016. Cox models were used to assess the impact of PORT and LNR on OS adjusted for patient characteristics and treatment information. RESULTS: Among 4,050 patients, 1,728 (42.7%) had PORT. There was increased use of IMRT in the more recent period (53.8% in 2010-2016 vs 24.0% in 2004-2009). PORT was associated with better OS in the overall cohort. For patients with inadequate lymph node dissection (LND), PORT marginally improved OS (HR = 0.91, p = 0.058). Among patients with adequate LND, PORT did not improve OS for patients with LNR <15% (HR = 1.11, p = 0.21), or LNR 15-29% (HR = 1.03, p = 0.73), but it significantly improved OS for patients with LNR ≥30% (HR = 0.83, p = 0.006). In patients with LNR≥30%, IMRT significantly improved OS when compared to no PORT (HR = 0.75, p < 0.05) while 3D RT did not (HR = 0.89, p = 0.32). CONCLUSIONS: PORT was associated with better survival for pN2 NSCLC patients after R0 resection, adequate LND with high LNR, after accounting for multiple confounders. Among the whole cohort, most of the OS benefits of PORT were driven by patients with inadequate LND, high LNR or use of IMRT.

A multidisciplinary management algorithm for brain metastases.

The incidence of brain metastases continues to present a management issue despite the advent of improved systemic control and overall survival. While the management of oligometastatic disease (ie, 1-4 brain metastases) with surgery and radiation has become fairly straightforward in the era of radiosurgery, the management of patients with multiple metastatic brain lesions can be challenging. Here we review the available evidence and provide a multidisciplinary management algorithm for brain metastases that incorporates the latest advances in surgery, radiation therapy, and systemic therapy while taking into account the latest in precision medicine-guided therapies. In particular, we argue that whole-brain radiation therapy can likely be omitted in most patients as up-front therapy.

Characterization of TR-107, a novel chemical activator of the human mitochondrial protease ClpP.

We recently described the identification of a new class of small-molecule activators of the mitochondrial protease ClpP. These compounds synthesized by Madera Therapeutics showed increased potency of cancer growth inhibition over the related compound ONC201. In this study, we describe chemical optimization and characterization of the next generation of highly potent and selective small-molecule ClpP activators (TR compounds) and demonstrate their efficacy against breast cancer models in vitro and in vivo. We selected one compound (TR-107) with excellent potency, specificity, and drug-like properties for further evaluation. TR-107 showed ClpP-dependent growth inhibition in the low nanomolar range that was equipotent to paclitaxel in triple-negative breast cancer (TNBC) cell models. TR-107 also reduced specific mitochondrial proteins, including OXPHOS and TCA cycle components, in a time-, dose-, and ClpP-dependent manner. Seahorse XF analysis and glucose deprivation experiments confirmed the inactivation of OXPHOS and increased dependence on glycolysis following TR-107 exposure. The pharmacokinetic properties of TR-107 were compared with other known ClpP activators including ONC201 and ONC212. TR-107 displayed excellent exposure and serum t1/2 after oral administration. Using human TNBC MDA-MB-231 xenografts, the antitumor response to TR-107 was investigated. Oral administration of TR-107 resulted in a reduction in tumor volume and extension of survival in the treated compared with vehicle control mice. ClpP activation in vivo was validated by immunoblotting for TFAM and other mitochondrial proteins. In summary, we describe the identification of highly potent new ClpP agonists with improved efficacy against TNBC, through targeted inactivation of OXPHOS and disruption of mitochondrial metabolism.

Race Does Not Affect Survival in Patients With Prostate Cancer Treated With Radiation Therapy.

BACKGROUND/AIM: Recent evidence has shown that African American men with prostate cancer may have more radiosensitive disease with greater overall survival (OS) with radiotherapy compared to Caucasian men. We compared OS in African American and Caucasian men receiving radiotherapy utilizing the National Cancer Database. PATIENTS AND METHODS: African American or Caucasian men with N0M0 prostate adenocarcinoma diagnosed between 2004 and 2013 were selected and grouped into favorable and unfavorable risk based on clinical T-stage, clinical Gleason score, and prostate-specific antigen. Patients with favorable risk received brachytherapy or dose-escalated external beam radiation (EBRT); those with unfavorable risk received EBRT plus anti-androgen therapy with/without brachytherapy. African American and Caucasian men in each subgroup were propensity score-matched and analyzed for survival. Sensitivity analysis used treatment-race and age-race interaction terms. RESULTS: 27,150 patients met the inclusion criteria, with a median age of 68 (range=38-90) years and median follow-up of 59.93 (range=48-142.62) months. OS was equivalent between African American and Caucasian race in favorable risk [log-rank p=0.82; hazard ratio (HR)=0.928; 95% confidence intervaI (CI)=0.583-1.477, p=0.753] and unfavorable-risk subgroups (log-rank p=0.87, HR=1.078, 95% CI=0.843-1.379, p=0.550). No significant interaction existed between treatment and race for either cohort but there was a significant interaction between race and age in those with unfavorable risk (HR=1.046, 95% CI=1.009-1.084, p=0.015), with greater OS in those of Caucasian race ≤60 years (HR=0.320, 95% CI=0.137-0.752, p=0.009). CONCLUSION: African American and Caucasian men have similar survival when treated with risk-appropriate definitive radiotherapy. However, younger (age ≤60 years) African American men with unfavorable risk have poorer survival than their Caucasian counterparts and may harbor a significantly different biology of disease.

Racial and Socioeconomic Disparities in the Treatments and Outcomes of Pancreatic Cancer Among Different Treatment Facility Types.

OBJECTIVES: The aim of this study was to investigate racial and socioeconomic disparities for patients with pancreatic cancer across different facility types. METHODS: The National Cancer Database was queried for pancreatic cancer cases from 2004 to 2015. Along with propensity score matching analysis, multivariate logistic and Cox model were used to assess effects of facility type, race, elements of socioeconomics on receipt of treatment, time to treatment, and overall survival, separately. RESULTS: Among 223,465 patients, 44.6%, 42.1%, and 13.3% were treated at academic, community, and integrated facilities, respectively. Private insurance was associated with more treatment (odds ratio, 1.41; P < 0.001) and better survival [hazards ratio (HR), 0.84; P < 0.001]. Higher education was associated with earlier treatment (HR, 1.09; P < 0.001). African Americans had less treatment (odds ratio, 0.97; P = 0.04) and delayed treatment (HR, 0.89; P < 0.001) despite later stage at diagnosis. After adjusting for socioeconomic status, African Americans had similar survival (HR, 0.99; P = 0.11) overall and improved survival (HR, 0.95; P = 0.016) at integrated facilities. CONCLUSIONS: Higher socioeconomic status was associated with better treatment and survival. After adjusting for socioeconomic disparities, race did not affect survival. Less racial disparity was observed at integrated facilities.

The Value of Total Lymph Nodes Examined and Number of Positive Lymph Nodes in Determining the Role of Adjuvant Radiation in Pancreatic Cancer Patients.

OBJECTIVES: The aim of this study was to determine the survival benefits by adjuvant radiation therapy (RT) in pancreatic cancer patients with different total lymph nodes examined (TNE), number of positive lymph nodes (NPN), and lymph nodes ratio (LNR). METHODS: National Cancer Database was queried for nonmetastatic pancreatic cancer patients from 2004 to 2015. Cox models were utilized. Interaction terms were applied to evaluate the effect of RT in different NPN, LNR, and margin strata. Multivariate analysis was performed. RESULTS: Of 19,759 patients identified, 10,910 patients qualified. Compared with TNE of 1 to 9, TNE of 10 to 14, 15 to 19, 20 to 24, and 25 or greater had progressive overall survival (OS) benefits. Adjuvant RT had similar OS benefits among them. In negative margin patients, adjuvant RT improved OS when NPN was 2 to 3 (hazards ratio [HR], 0.84; P = 0.01) or LNR was 0.15 to 0.25 (HR, 0.79; P = 0.002). In positive margin patients, adjuvant RT nonsignificantly improved OS when NPN was 1 to 3 (HR, 0.89; P = 0.36) or when NPN was 4 or greater (HR, 0.79; P = 0.07). CONCLUSIONS: Higher TNE correlates with better survival. Adjuvant RT may not compensate for inadequate lymph node dissection. Adjuvant RT improves survival in negative-margin patients with 2 to 3 positive lymph nodes or LNR of 0.15 to 0.25.

Radical Prostatectomy Without Pelvic Lymph Node Dissection Is Widely Practiced in High-Risk Patients Despite Poorer Survival.

PURPOSE: Radical prostatectomy with pelvic lymph node dissection (PLND) is the standard of care for unfavorable risk prostate cancer. We investigated dissection practice patterns and their impact on overall survival using a large national database. PATIENTS AND METHODS: Men with prostate adenocarcinoma diagnosed between 2004 and 2013 were identified from the National Cancer Data Base. Disease was classified as either favorable or unfavorable on the basis of National Comprehensive Cancer Network guidelines. Minimum follow-up was 4 years. All patients received risk-appropriate surgery: prostatectomy with or without PLND. Prostatectomy alone and prostatectomy with PLND was propensity score matched within each risk cohort. Survival analysis included Kaplan-Meier statistics, Cox proportional hazards model, and multivariate logistic regression. RESULTS: A total of 66,469 subjects met the inclusion criteria. Median (range) age was 63 (27-90) years. Median (range) follow-up was 59.53 (48-143.54) months. Within the cohort of patients with favorable risk disease, 51% did not undergo nodal dissection. Matched analysis demonstrated no difference in survival (P = .926). Within the cohort of patients with unfavorable risk disease, 39.2% did not receive nodal dissection. Matched analysis demonstrated that nodal dissection had superior survival (log-rank P = .002; hazard ratio = 0.624; 95% confidence interval, 0.466-0.835; P = .002). Greater odds of receiving nodal dissection included an open or robot-assisted approach compared to a laparoscopic approach, academic/research programs, and higher risk groups. CONCLUSION: Although PLND is associated with a significant survival benefit in men with unfavorable risk prostate cancer, nearly 40% of patients with unfavorable risk disease did not receive PLND.

Treatment patterns and outcomes among women with brain metastases from gynecologic malignancies.

BACKGROUND: Brain metastasis secondary to gynecologic malignancy is rare and has no definitive management guidelines. In this descriptive study, we aimed to identify prognostic factors and treatments that may be associated with longer overall survival. METHODS: Patients with brain metastases from gynecologic malignancies were identified between 2004 and 2019 at two institutions. Descriptive statistics were performed using N (%) and median (interquartile range). Univariate cox proportional hazards regression was performed to evaluate the effect of different factors on overall survival. RESULTS: 32 patients presented with brain metastasis from gynecologic primaries (ovarian/fallopian tube/primary peritoneal n = 14, uterine n = 11, cervical n = 7). Median age of initial cancer diagnosis was 61 (34-79). At initial cancer diagnosis 83% of patients were Stage III/IV and underwent surgery (66%), chemotherapy (100%), and/or pelvic radiation (33%). Median time from initial cancer diagnosis to brain metastasis was 18 months. Treatment of brain metastasis with surgery and radiation compared to stereotactic radiosurgery or whole brain radiation therapy alone revealed a trend toward longer overall survival (p = 0.07). Time from initial cancer diagnosis to brain metastasis was associated with longer overall survival with each one-month increase from initial cancer diagnosis associated with a 7% reduction in risk of death (HR 0.93, 95% CI = 0.89-0.97, p = 0.01). Initial cancer treatment, stage, histology, and number of brain lesions did not affect overall survival. CONCLUSIONS: Patients with brain metastasis secondary to gynecologic malignancies with the longest overall survival had the greatest lag time between initial cancer diagnosis and brain metastasis. Brain metastasis treated with surgery and radiation was associated with longer overall survival.

Percutaneous tumor curettage and interstitial delivery of samarium-153 coupled with kyphoplasty for treatment of vertebral metastases.

OBJECT: The object of this study was to investigate the use of a minimally invasive technique for treating metastatic tumors of the vertebral body, aimed at relieving pain, preventing further tumor growth, and minimizing the adverse effects of systemic use of samarium-153 ((153)Sm). METHODS: The procedure is performed in the same fashion as a kyphoplasty, using a unilateral extrapedicular approach under local anesthesia/mild general sedation, with the patient in the lateral decubitus position. The tumor is accessed as in a standard kyphoplasty. The side is chosen according to the location of the metastasis. Prior to inflation of the balloon the tumor is debulked by percutaneous curettage. Balloon inflation is carried out as per standard kyphoplasty in an attempt to create a larger space and reduce a possible kyphotic deformity. Three mCi of (153)Sm-EDTMP (ethylenediaminetetramethylenephosphonic acid) is then mixed with bone cement (polymethylmethacrylate) and injected into the void created by the balloon tamp. RESULTS: Twenty-four procedures were performed in 19 patients. There was reliable and reproducible delivery of the radiolabeled (153)Sm-EDTMP to the metastatic site, without spillage. The procedure was safe. There were no procedure-related complications. There was no hematological toxicity with the low doses of (153)Sm used. Pain improved in all patients. The long-term results related to tumor control continue to be investigated. CONCLUSIONS: Combined percutaneous debulking of confined vertebral metastases and administration of local (153)Sm is feasible and safe. Furthermore, this technique leads to immediate relief of cancer-related pain and may help prevent or slow down the progression of vertebral metastatic tumors.

The effect of brain metastasis location on clinical outcomes: A review of the literature.

It is common clinical practice to consider the location of a brain metastasis when making decisions regarding local therapies and, in some scenarios, estimating clinical outcomes, such as local disease control and patient survival. However, the location of a brain metastasis is not included in any validated prognostic nomogram and it is unclear if this is due to a lack of a relationship or a lack of support from published data. We performed a comprehensive review of the literature focusing on studies that have investigated a relationship between brain metastasis location and clinical outcomes, including patient survival. The vast majority of reports anatomically categorized brain metastases as supratentorial or infratentorial whereas some reports also considered other subdivisions of the brain, including different lobes or with particular areas defined as eloquent cortex. Results were variable across studies, with some finding a relationship between metastasis location and survival, but the majority finding either no relationship or a weak correlation that was not significant in the context of multivariable analysis. Here, we highlight the key findings and limitations of many studies, including how neurosurgical resection might influence the relative importance of metastasis location and in what ways future analyses may improve anatomical categorization and resection status.

Challenging AJCC 8 Staging for Soft Tissue Sarcoma Using the NCDB.

PURPOSE: To determine whether the new American Joint Committee on Cancer (AJCC) 8 grouping of soft tissue sarcoma (STS) with nodal disease (N1M0) and metastatic disease (M1) as stage IV correctly represents the prognosis of these previously separate patient groups, using the National Cancer Database. METHODS AND MATERIALS: Adults with STS identified in the 2004 to 2014 National Cancer Database, classified by the World Health Organization 2013 system into 10 histologic subgroups, were grouped according to AJCC 8 staging and analyzed according to demographic characteristics, histology, primary site, disease extent, and adjuvant treatment. Primary retroperitoneal sites, "other/unusual" histologic subgroups, and those with delays in therapy (>180 days from diagnosis) were excluded. We used χ2 tests, Cox proportional hazard models, and propensity-score matched analyses. RESULTS: Of 82,987 patients identified, 55,417 met inclusion criteria; 29,855 (53.9%) were male, and 25,262 (46.1%) were female. Median age was 60 years (range, 18-90 years). Overall survival (OS) of STS of all sites was significantly different between N1M0 and N0-1M1 patients at 5 years (34.4%; [95% confidence interval {CI}, 30.1%-38.8%] vs 10.1% [95% CI, 9%-11%], respectively) and 10 years (27.3% [95% CI, 22.5%- 32.2%] vs 5.4% [95% CI, 4.5%-6.5%], respectively; log-rank test, P < .001). For STS of trunk and extremities in N1M0 and N0-1M1 patients, the N1M0 cohort was associated with significantly greater OS on multivariate Cox proportional hazards models (hazard ratio, 0.48; 95% CI, 0.41-0.58; P < .001), and this OS difference remained significant for propensity-matched cohorts of all primary sites (HR, 0.53; 95% CI, 0.44-0.64; P < .001). CONCLUSIONS: In adult STS, including those of the trunk and extremity, OS is superior with N1M0 compared with N0-1M1 disease. These results suggest that the AJCC 8th edition grouping of N1 and M1 patients into stage IV may obscure the more favorable prognosis of patients with N1M0 disease.

A low percentage of metastases in deep brain and temporal lobe structures.

BACKGROUND: Whole-brain radiotherapy (WBRT) in patients with brain metastases (BM) is associated with neurocognitive decline. Given its crucial role in learning and memory, efforts to mitigate this toxicity have mostly focused on sparing radiation to the hippocampus. We hypothesized that BM are not evenly distributed across the brain and that several additional areas may be avoided in WBRT based on a low risk of developing BM. METHODS: We contoured 2757 lesions in a large, single-institution database of patients with newly diagnosed BM. BM centroids were mapped onto a standard brain atlas of 55 anatomic subunits and the observed percentage of BM was compared with what would be expected based on that region's volume. A region of interest (ROI) analysis was performed in a validation cohort of patients from 2 independent institutions using equivalence and one-sample hypothesis tests. RESULTS: The brainstem and bilateral thalami, hippocampi, parahippocampal gyri, amygdala, and temporal poles had a cumulative risk of harboring a BM centroid of 4.83% in the initial cohort. This ROI was tested in 157 patients from the validation cohort and was found to have a 4.1% risk of developing BM, which was statistically equivalent between the 2 groups (P < 1 × 10-6, upper bound). CONCLUSION: Several critical brain structures are at a low risk of developing BM. A risk-adapted approach to WBRT is worthy of further investigation and may mitigate the toxicities of conventional radiation.

Mitochondrial Protease ClpP is a Target for the Anticancer Compounds ONC201 and Related Analogues.

ONC201 is a first-in-class imipridone molecule currently in clinical trials for the treatment of multiple cancers. Despite enormous clinical potential, the mechanism of action is controversial. To investigate the mechanism of ONC201 and identify compounds with improved potency, we tested a series of novel ONC201 analogues (TR compounds) for effects on cell viability and stress responses in breast and other cancer models. The TR compounds were found to be ∼50-100 times more potent at inhibiting cell proliferation and inducing the integrated stress response protein ATF4 than ONC201. Using immobilized TR compounds, we identified the human mitochondrial caseinolytic protease P (ClpP) as a specific binding protein by mass spectrometry. Affinity chromatography/drug competition assays showed that the TR compounds bound ClpP with ∼10-fold higher affinity compared to ONC201. Importantly, we found that the peptidase activity of recombinant ClpP was strongly activated by ONC201 and the TR compounds in a dose- and time-dependent manner with the TR compounds displaying a ∼10-100 fold increase in potency over ONC201. Finally, siRNA knockdown of ClpP in SUM159 cells reduced the response to ONC201 and the TR compounds, including induction of CHOP, loss of the mitochondrial proteins (TFAM, TUFM), and the cytostatic effects of these compounds. Thus, we report that ClpP directly binds ONC201 and the related TR compounds and is an important biological target for this class of molecules. Moreover, these studies provide, for the first time, a biochemical basis for the difference in efficacy between ONC201 and the TR compounds.

The impact of positron emission tomography/computed tomography in edge delineation of gross tumor volume for head and neck cancers.

PURPOSE: To study anatomic biologic contouring (ABC), using a previously described distinct halo, to unify volume contouring methods in treatment planning for head and neck cancers. METHODS AND MATERIALS: Twenty-five patients with head and neck cancer at various sites were planned for radiation therapy using positron emission tomography/computed tomography (PET/CT). The ABC halo was used in all PET/CT scans to contour the gross tumor volume (GTV) edge. The CT-based GTV (GTV-CT) and PET/CT-based GTV (GTV-ABC) were contoured by two independent radiation oncologists. RESULTS: The ABC halo was observed in all patients studied. The halo had a standard unit value of 2.19 +/- 0.28. The mean halo thickness was 2.02 +/- 0.21 mm. Significant volume modification (>or=25%) was seen in 17 of 25 patients (68%) after implementation of GTV-ABC. Concordance among observers was increased with the use of the halo as a guide for GTV determination: 6 patients (24%) had a

Ionizing radiation induces EphA2 S897 phosphorylation in a MEK/ERK/RSK-dependent manner.

PURPOSE: The EphA2 tyrosine kinase is frequently overexpressed in human tumors that are also treated with radiation. However, few studies have examined the effect of radiation on the EphA2 receptor itself. The purpose of this project was to investigate the impact of radiation on EphA2 to better understand mechanisms of radioresistance. MATERIALS AND METHODS: Cell lines were exposed to X-rays and assayed for changes in EphA2 protein levels and phosphorylation over time by Western blotting. HEK293 cells stably expressing wild-type EphA2 or the S897A mutant were analyzed for cell survival from X-rays. RESULTS: Treatment of different cancer cell lines with 2 Gy of X-rays induced the phosphorylation of EphA2 on S897 but no changes were found in EphA2 total levels or its tyrosine phosphorylation. Radiation-induced S897 phosphorylation was unaffected by an AKT inhibitor but blocked by a MEK or RSK inhibitor. HEK293 cells expressing the EphA2 S897A mutant had a nearly 2-fold lower level of cell survival from X-rays than cells expressing wild-type EphA2. CONCLUSIONS: These findings show that radiation induces S897 EphA2 phosphorylation, an event associated with increased cell survival. Therefore, targeting pathways that mediate EphA2 S897 phosphorylation may be a beneficial strategy to reduce radioresistance.

Brachytherapy improves outcomes in young men (≤60 years) with prostate cancer: A SEER analysis.

PURPOSE: The aim of the study was to compare prostate cancer-specific mortality (PCSM) in young men with clinically localized prostate cancer treated by either external beam radiation (EBRT) alone or brachytherapy with or without external beam radiation. METHODS AND MATERIALS: Utilizing the Surveillance, Epidemiology and End Results database, 15,505 patients ≤60 years of age diagnosed with prostate cancer between 2004 and 2009 and treated with radiation therapy alone were identified. Incidence of PCSM was determined for both groups and compared using competing risk models. RESULTS: The overall 8-year PCSM for the study population was 1.9% (95% confidence interval [CI]: 1.6-2.2). For patients treated with EBRT or brachytherapy with or without external beam, the 8-year PCSM was found to be 2.8% (CI: 2.2-3.4) and 1.2% (CI: 0.9-1.6), respectively (p < 0.001). Univariable analysis demonstrated that brachytherapy was associated with lower PCSM risk (hazard ratio = 0.40; CI: 0.30-0.54; p < 0.001). High Gleason risk category, black race, higher Tumor (T) stage, and higher grade were all associated with greater mortality risk (p < 0.01). On multivariable analysis, brachytherapy continued to be associated with a significantly lower mortality risk (hazard ratio = 0.65; CI: 0.47-0.89; p = 0.008). Subgroup analyses found that among those with Gleason score ≥8, younger patients had increased risk of PCSM (p = 0.001). CONCLUSIONS: In men ≤60 years of age with prostate cancer, radiation therapy continues to offer excellent outcomes. After adjusting for relevant variables, the use of brachytherapy was associated with reduced PCSM compared to treatment with EBRT alone.