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The article discusses prostate cancer is the most common malignancy in men and the second leading cause of cancer mortality in men. Topics include advanced prostate cancer has a long natural history with continuous exposure to therapies that have impactful effects on overall health; radiation techniques have evolved, resulting in a reduced rate of acute and late toxicities; and the main drivers of prostate cancer cell growth and survival are androgens.

OBJECTIVE: The role of radiation therapy (RT) in the setting of surgically resected ampullary adenocarcinoma (AA) is not well defined. We examined the association of RT with survival in resected AA. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (8.2.1) was queried for patients with surgically resected AA diagnosed between 2004–2012 and aged = 20 years treated with or without RT. Patients were excluded if they had metastatic disease. Patients who were considered to be at high risk (defined as T4 or N+) were analyzed as a separate subgroup. Baseline characteristics were compared using the chi-squared test. Overall survival (OS) and cause-specific survival (CSS) were analyzed by Kaplan-Meier method and compared using log-rank test. Multivariable analysis with Cox regression was used to assess the association of survival and variables, including T stage, N stage, grade, age, and RT. RESULTS: A total of 2,034 patients with surgically resected AA were identified. Overall, 25.1% of patients received RT. Patients who received RT were younger (P < .001) and had higher T stage (P < .001), N stage (P < .001), and tumor grade (P < .001). At 5 years, RT use was associated with a worse OS (35.1% vs 43.4%; P =.050) and CSS (41.1% vs 52.5%; P =.005) in the overall cohort on univariate analysis. In the multivariate analysis, RT was not found to be detrimental to OS (hazard ratio [HR], 0.891 [95% CI, 0.763–1.041]) or CSS (HR, 0.811 [95% CI, 0.744–1.044]). A high-risk cohort of 1,129 patients was identified with T4 or N+ disease, of whom 35.8% received RT. At 5 years, RT was associated with improved OS (30.9% vs 24.2%; P =.001) and CSS (35.5% vs 30.9%; P =.016) on univariate analysis in this high-risk group. In the multivariate analysis, RT maintained its association with improved OS (HR, 0.784 [95% CI, 0.660–0.930]) and CSS (HR, 0.794 [95% CI, 0.661–0.954]) in this group. CONCLUSION: RT is associated with improved survival in surgically resected pT4 or N+ patients with AA. [ABSTRACT FROM AUTHOR]

Presents a response by Kevin A. Shulman et al to a letter to the editor about their study on reducing high blood cholesterol levels with drugs.

Purpose/objective(s): The PORTEC3 trial demonstrated a benefit for the use of adjuvant chemoradiation therapy (CRT) over whole pelvic radiotherapy (WPRT) in high risk endometrial cancer. While this trial included patients from Stage IB-III, unplanned subgroup analysis suggested the largest benefit in Stage III patients. This National Cancer Database (NCDB) analysis was performed to evaluate the staged-based differential benefit of CRT over WPRT across a broader number of patients with high-risk endometrial cancer.Materials/methods: Patients with endometrioid adenocarcinoma who underwent hysterectomy were identified in the NCDB from 2004 to 2017 who met enrollment criteria on the PORTEC3 trial: FIGO 2009 stage IA grade 3 with LVI, stage IB grade 3, stage II, stage IIIA, IIIB, or stage IIIC disease. Only patients receiving WPRT with or without chemotherapy were evaluated. Patients receiving chemotherapy alone or no adjuvant therapy were excluded. Chi-square analyses were performed to evaluate differences between patients receiving WPRT versus CRT. Kaplan-Meier survival analyses were performed and compared via log-rank analyses.Results: A total of 11,315 patients were analyzed, of which 7,334 (64.8%) patients received WPRT and 3,981 (35.2%) received WPRT and chemotherapy. Of patients receiving WPRT alone compared CRT, more patients were age 65 or greater (44.7% vs 36.0%, P < 0.001). Lymphovascular invasion (66.9% vs 52.8%, P < 0.001) and lymph node positivity were more common (58.7% vs 29.1%, P < 0.001) in patients receiving CRT versus WPRT alone. 5-year overall survival was improved in Stage III patients receiving CRT compared to those receiving radiation alone (76.2% vs 72.4%, P < 0.001). 5-year overall survival was not different in stage I-II patients receiving WPRT and chemotherapy versus WPRT alone (76.7% vs 77.7%, P = .91).Conclusion: The addition of chemotherapy to WPRT improves overall survival in stage III patients or greater with endometrioid adenocarcinoma but not in patients with high-risk, stage I-II disease.Author Disclosure: E. Yu: None. T.A. DiPetrillo: Patent/License Fees/Copyright; Thomas DiPetrillo. P.P. Koffer: None. C.J. Miller: None. [ABSTRACT FROM AUTHOR]

Identifying factors associated with COVID-19 vaccination acceptance among vulnerable groups, including autistic individuals, can increase vaccination rates and support public health. The purpose of this study was to determine differences among autistic adults who reported COVID-19 vaccination acceptance from those who did not. In this study we describe COVID-19 vaccination status and self-reported preferences among autistic adults and identify related factors. Vaccine accepters were more likely to report increased loneliness during COVID-19, lived in more populous counties (p = 0.02), and lived in counties won by President Biden in the 2020 US presidential election (p < 0.001). Positive correlations were found between desire to protect others, concern about contracting COVID-19, and trusting vaccine safety (p < 0.001). Concern about vaccine safety was common among the vaccine hesitant, while lack of concern about COVID-19 overall was not. Identifying health promotion strategies based on self-reported, lived experiences about COVID-19 among vulnerable groups is key for public health impact. [ABSTRACT FROM AUTHOR]

Background: With the increasing prevalence of autistic individuals, it is greatly needed to examine the factors impacting their community participation experiences. Where autistic adults live and how that may be related to their participation and quality of life is one environmental factor that has received little attention.Aims: This study explored the association between living arrangements in the community and community participation for autistic adults.Method: This study used data from a statewide survey of autistic adults (N = 744) to investigate the relationship between living arrangements (live alone with or without support, live with roommate/spouse, or live with family) and the amount, breadth, and sufficiency of community participation.Results: After controlling for sociodemographic and clinical factors known to be associated with community participation, autistic adults living with family members participated less frequently in community activities over 30 days than those living with a roommate/spouse. However, they experienced similar levels of sufficiency with their participation. Autistic adults living alone with support reported the lowest levels of sufficiency with their participation, although the amount and breadth of their participation were no different from other adults.Conclusion: These findings have several implications for providing support to enable autistic adults to participate in the areas that are important to them and to the extent they desire. Future research is needed to gain a better understanding of how interests and expectations for participation may be influenced by living situations. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Lobectomy followed by adjuvant chemotherapy is the standard of care for patients with clinically T1-T2N1 non-small cell lung cancer (NSCLC). However, the optimal treatment of patients who cannot undergo or refuse to undergo surgical resection is controversial. Currently, NCCN guidelines recommend concurrent chemoradiation; however, limited evidence exists to substantiate this recommendation for this particular patient population. Many groups advocate for radiation alone with standard or hypofractionated approaches. We hypothesized that concurrent chemoradiation would be associated with longer overall survival (OS) compared to hypofractionated or conventionally fractionated radiation.Materials/methods: We queried the National Cancer Database (NCDB) for patients with cT1-T2N1M0 NSCLC treated non-surgically with definitive radiation or concurrent chemoradiation between 2004 and 2016. We further restricted our cohort to patients receiving RT doses with an EQD2 ≥ 58.4 Gy and > 5 fractions. Patients were divided into four treatment groups: standard fractionated radiation (SFRT), hypofractionated radiation (HFRT), standard fractionated chemoradiation (SFRT+CT), and hypofractionated chemoradiation (HFRT+CT). Chemoradiation was defined as chemotherapy and radiation with start dates within 30 days. To address confounding by indication, inverse probability of treatment weights (IPTW) were constructed regressing sociodemographic, clinical, and facility characteristics on treatment group in a multinomial regression model. Weighted Cox proportional hazard regression models were then used to evaluate the relative hazard of death with SFRT set as the referent treatment group.Results: A total of 2,534 patients met inclusion criteria and of these 2,200 patients (57,462.83 person-months) had complete data for all confounders and were included in the analytic sample. Of the 2,200 patients 26.6% received SFRT, 7% received HFRT, 62.1% received SFRT+CT, and 4.2% received HFRT+CT. The median EQD2 (IQR) were: SFRT 66 Gy (60-68), HFRT 66.7 Gy (62.5-71.9), SFRT+CT 65.5 Gy (60-66), and HFRT+CT 67.6 Gy (65.1-72.3). 27% of patients were still alive 36 months after the initiation of RT (17.3% of SFRT, 20.3% of HFRT, 33.2% of SFRT+CT, and 21.8% of HFRT+CT). After IPTW propensity weighting, the probability of death at 3 years was compared between the treatment groups and only SFRT+CT was associated with longer OS. Compared with SFRT, the hazard ratio for all-cause mortality for those treated with SFRT+CT was 0.67 (95% CI: 0.57-0.75), for HFRT was 0.86 (95% CI: 0.61-1.06), and for HFRT+CT was 0.81 (95% CI 0.61-1.06).Conclusion: To our knowledge, this is the first large database propensity weighted analysis of patients with cT1-T2N1M0 NSCLC managed non-surgically with definitive radiation or chemoradiation. In this group, treatment with SFRT+CT is associated with longer OS relative to treatment with radiation alone. [ABSTRACT FROM AUTHOR]

Many proline-rich proteins participate in delivering actin monomers to specific cellular locations where actin-rich membrane protrusions, such as ruffles, filopodia and microspikes, are formed. These protrusions are necessary for cell motility. Actin monomer is usually delivered to the site of polymerization in the form of profilactin - a complex of G-actin with a polyproline-binding protein, profilin. Here, we describe proline-rich proteins involved in regulating actin polymerization and classify them according to their role in recruiting profilin to the membrane.

Treatment with metabolic inhibitors and addition of exogenous MgATP exerted different effects on secretion from streptolysin-O-permeabilized mast cells, responding to calcium and GTP-gamma-S as single effectors (i.e., independently of each other). These effects were also strongly dependent on the experimental conditions. Thus cells, triggered by Ca2+ at the time of permeabilization, did not require MgATP, but after metabolic inhibition rapidly became absolutely dependent on its provision, requiring high (> mM) concentrations. AMP-PNP was not effective. After longer treatment with metabolic inhibitors, the absolute dependence on MgATP was also exhibited by cells responding to dual effectors (i.e., Ca2+ and GTP-gamma-S applied together). In contrast, calcium independent secretion due to GTP-gamma-S was more resistant to metabolic inhibition, exhibiting no absolute requirements for MgATP. Once the responsiveness to GTP-gamma-S had been lost, it could not be restored by addition of MgATP. MgATP, in fact, inhibited the response of permeabilized cells to GTP-gamma-S. This effect could be mimicked by AMP-PNP. When permeabilized cells were washed before triggering, MgATP (0.1-1 mM concentration range) was no longer inhibitory but stimulatory. These differences between Ca(2+)- and GTP-gamma-S-induced responses indicate that ATP utilization is essential to the calcium, but not to the guanine nucleotide, pathway to secretion. The rate of the response to calcium/MgATP was much slower in the absence than in the presence of GTP-gamma-S. The onset of secretion occurred after an initial delay. This lag phase was abolished by addition of GTP-gamma-S, suggesting that a GTP-binding protein may control a reaction which constitutes a rate-limiting step in the secretory process.

Recent advances in the understanding of the terminal stages of the pathway of regulated secretion (exocytosis) have depended in large part on the use of permeabilized secretory cells in which the cytosol is directly accessible to manipulation from the outside. As well as Ca2+, a role for GTP, and hence a GTP-binding protein (GE), is plainly apparent in the exocytotic mechanism of some cells. In metabolically depleted and permeabilized mast cells, the combination of Ca2+ and a guanine nucleotide are a sufficient stimulus for the release of the total cell content of histamine and hexosaminidase. ATP is not required and so a phosphorylation reaction does not comprise a necessary step in the terminal pathway. Phosphorylating nucleotides, however, can modulate the exocytotic reaction in a manner that suggests that the reverse reaction, namely protein dephosphorylation, might be an enabling step. Support for this idea is derived from experiments in which the cells are conditioned to become responsive to Ca2+ alone; in these circumstances the dependence of secretion on the presence of a guanine nucleotide can be reimposed by okadaic acid, an inhibitor of protein phosphatases.