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The aim of this study was to analyze the patterns of prostate bed (PB) recurrence in prostate cancer patients experiencing prostate-specific antigen (PSA) persistence (BCP) or biochemical recurrence (BCR) after radical prostatectomy using 68Ga-PSMA-11 PET/CT (68Ga-PSMA PET) in relation to the Radiation Therapy Oncology Group (RTOG) clinical target volumes (CTVs). Methods: This single-center, retrospective analysis included patients with BCP or BCR after radical prostatectomy and PB recurrence on 68Ga-PSMA PET. The PB recurrences were delineated by nuclear medicine physicians, the CTVs by radiation oncologists contouring guidelines on the 68Ga-PSMA PET, respectively, masked from each other. The coverage of the 68Ga-PSMA PET recurrence was categorized as PSMA recurrence completely covered, partially covered, or not covered by the RTOG-based CTV. Further, we evaluated the differences in PSMA recurrence patterns among patients with different 68Ga-PSMA PET staging (miTNM). Mann-Whitney U tests, the chi-square test, and Spearman (ρ) correlation analysis were used to investigate associations between CTV coverage and 68Ga-PSMA PET-based tumor volume, serum PSA levels, miTNM, and rectal/bladder involvement. Results: A total of 226 patients were included in the analysis; 127 patients had PSMA recurrence limited to the PB (miTrN0M0), 30 had pelvic nodal disease (miTrN1M0), 32 had extrapelvic disease (miTrN0M1), and 37 had both pelvic nodal disease and extrapelvic disease (miTrN1M1). In the miTrN0M0 cohort, the recurrence involved the rectal and bladder walls in 12 of 127 (9%) and 4 of 127 (3%), respectively. The PSMA-positive PB recurrences were completely covered by the CTV in 68 of 127 patients (53%), partially covered in 43 of 127 (34%), and not covered in 16 of 127 (13%). Full coverage was associated with a smaller tumor volume (P = 0.043), a lack of rectal/bladder wall involvement (P = 0.03), and lower miTNM staging (P = 0.035) but not with lower serum PSA levels (P = 0.979). Conclusion: Our study suggests that 68Ga-PSMA PET can be a valuable tool for guiding salvage radiation therapy (SRT) planning directed to the PB in the setting of postoperative BCR or BCP. These data should be incorporated into the redefinition of PB contouring guidelines.

PurposeTo identify any clinical or dosimetric parameters that predict which individuals may benefit from on-table adaptation during pancreas stereotactic body radiotherapy (SBRT) with MRI-guided radiotherapy.Methods and materialsThis was a retrospective study of patients undergoing MRI-guided SBRT from 2016 to 2022. Pre-treatment clinical variables and dosimetric parameters on the patient's simulation scan were recorded for each SBRT course, and their ability to predict for on-table adaptation was analyzed using ordinal logistic regression. The outcome measure was number of fractions adapted.ResultsSixty-three SBRT courses consisting of 315 fractions were analyzed. Median prescription dose was 40 Gy in five fractions (range, 33-50 Gy); 52% and 48% of courses were prescribed ≤40 Gy and >40 Gy, respectively. The median minimum dose delivered to 95% (D95) of the gross tumor volume (GTV) and planning target volume (PTV) was 40.1 Gy and 37.0 Gy, respectively. Median number of fractions adapted per course was three, with 58% (183 out of 315) total fractions adapted. On univariable analysis, the prescription dose (>40 Gy vs ≤40 Gy), GTV volume, stomach V20 and V25, duodenum V20 and dose maximum, large bowel V33 and V35, GTV dose minimum, PTV dose minimum, and gradient index were significant determinants for adaptation (all p

IntroductionOsimertinib is an effective treatment for metastatic NSCLC. Occasionally, thoracic radiation therapy (TRT) is delivered to patients receiving osimertinib to treat residual or progressing pulmonary tumors. Anecdotal reports suggest that the delivery of TRT in combination with osimertinib may be associated with a high risk of severe pneumonitis.MethodsA retrospective study was performed at a single academic medical center in the United States to investigate the incidence of severe pneumonitis among patients treated with combined TRT and osimertinib between June 2016 and December 2021. Baseline patient characteristics, tumor size and location, and dosimetric parameters were evaluated. The highest grade of radiation pneumonitis that developed within 6 months of treatment was scored in accordance with the Common Terminology Criteria for Adverse Events version 5.0.ResultsA total of 16 patients were identified who were treated with combined TRT and osimertinib. All had a diagnosis of metastatic NSCLC. Treatment-related grade greater than or equal to 2 pneumonitis developed in 56%, grade greater than or equal to 3 in 37.5%, and grade 4 in 6.3%; no patient developed grade 5 pneumonitis. Median time to any-grade pneumonitis was 29 days (1-84 d); all patients had symptom resolution with expectant management or oral steroid therapies. All patients discovered to have grade greater than or equal to 3 pneumonitis (n = 6) received TRT to tumors located within 2 cm of the proximal bronchial tree, including tumors abutting the proximal bronchial tree (n = 2) and within the mediastinum (n = 1).ConclusionsThe combination of TRT with osimertinib was associated with a high rate of severe pneumonitis that required oral steroid medications. Larger studies are needed to validate these findings and to understand the clinical and treatment factors that influence this risk and how they can be mitigated.

Non-small cell lung cancer (NSCLC) has a high rate of brain metastasis. The purpose of this study was to assess the differential distribution of brain metastases from primary NSCLC based on mutation status. Brain MRI scans of patients with brain metastases from primary NSCLC were retrospectively analyzed. Brain metastatic tumors were grouped according to mutation status of their primary NSCLC and the neuroimaging features of these brain metastases were analyzed. A total of 110 patients with 1386 brain metastases from primary NSCLC were included in this study. Gray matter density at the tumor center peaked at ~0.6 for all mutations. The median depths of tumors were 7.9 mm, 8.7 mm and 9.1 mm for EGFR, ALK and KRAS mutation groups, respectively (p = 0.044). Brain metastases for the EGFR mutation-positive group were more frequently located in the left cerebellum, left cuneus, left precuneus and right precentral gyrus. In the ALK mutation-positive group, brain metastases were more frequently located in the right middle occipital gyrus, right posterior cingulate, right precuneus, right precentral gyrus and right parietal lobe. In the KRAS mutation-positive patient group, brain metastases were more frequently located in the posterior left cerebellum. Our study showed differential spatial distribution of brain metastases in patients with NSCLC according to their mutation status. Information regarding distribution of brain metastases is clinically relevant as it could be helpful to guide treatment planning for targeted therapy, and for predicting prognosis.

BackgroundPatients with prostate cancer treated with stereotactic body radiation therapy (SBRT) may experience gastrointestinal (GI) toxicity. The hydrogel may mitigate this toxicity by reducing the rectal radiation dose. The purpose of this study is to compare rectal radiation dose and GI toxicity in patients receiving prostate SBRT with and without hydrogel.MethodsConsecutive patients treated with SBRT between February 2017 and January 2020 with and without hydrogel were retrospectively identified. Baseline characteristics including prostate volume, rectal diameter, body mass index (BMI), age, pretreatment prostate-specific antigen (PSA), Gleason score, T-stage, and androgen deprivation therapy (ADT) usage were compared. Dosimetric outcomes (V40Gy, V36Gy, V32Gy, V38Gy, and V20Gy), rates of acute (≤90 days) and late (>90 days) GI toxicity, and PSA outcomes were evaluated for patients with and without hydrogel.ResultsA total of 92 patients were identified (51 hydrogel and 41 non-hydrogel). There were no significant differences in baseline characteristics. Rectal V38(cc) was significantly less in the hydrogel group (mean 0.44 vs. mean 1.41 cc, p = 0.0002), and the proportion of patients with V38(cc) < 2 cc was greater in the hydrogel group (92% vs. 72%, p = 0.01). Rectal dose was significantly lower for all institutional dose constraints in the hydrogel group (p < 0.001). The hydrogel group experienced significantly less acute overall GI toxicity (16% hydrogel vs. 28% non-hydrogel, p = 0.006), while the difference in late GI toxicity trended lower with hydrogel but was not statistically significant (4% hydrogel vs. 10% non-hydrogel, p = 0.219). At a median follow-up of 14.8 months, there were no biochemical recurrences in either group.ConclusionHydrogel reduces rectal radiation dose in patients receiving prostate SBRT and is associated with a decreased rate of acute GI toxicity.

PurposeStereotactic body radiotherapy (SBRT) delivers ablative doses with excellent local control. However, implementing SBRT for abdominal and pelvic tumors has been limited by the risk for treatment-related gastrointestinal toxicity. MRI-guided radiotherapy may ameliorate these risks and increase the therapeutic ratio. We report the clinical outcomes of stereotactic MRI-guided adaptive radiotherapy (SMART) for primary and metastatic tumors in the abdomen and pelvis.MethodsFrom November 2014 to August 2017, the first 106 consecutive patients with 121 tumors in the abdomen and pelvis were treated with SMART at a single institution. Of the cohort, 41.5%, 15.1%, and 43.4% had primary, locally recurrent, and oligometastatic tumors, respectively. SMART was delivered using a tri-cobalt-60 gantry with on-board 0.35 Tesla MRI with respiratory breath-hold and daily adaptive re-planning when anatomically necessary. A median of 40Gy in five fractions was prescribed. The Common Terminology Criteria for Adverse Events v.4.03 was used to score treatment-related toxicities. Local control (LC), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier method.ResultsOf the 510 treatments, seventy-one (13.9%) were adapted. Fatigue, nausea, and pain were the most common acute toxicities. 0.9 and 0% of patients experienced acute grade three and four toxicities, respectively. 5.2 and 2.1% of patients experienced late grade three and four toxicities, respectively. After a median follow-up of 20.4 months, the 2-year LC rate was 74% on a per-lesion basis. Two-year LC was 96% for lesions that were treated with BED10 ≥100 versus 69% for BED10

PurposeThough utilization of medical procedures has been shown to vary considerably across the United States, similar efforts to characterize variation in the delivery of radiation therapy (RT) procedures have not been forthcoming. Our aim was to characterize variation in the delivery of common RT procedures in the Medicare population. We hypothesized that delivery would vary significantly based on provider characteristics.MethodsThe Centers for Medicare and Medicaid Services (CMS) Physician and Other Supplier Public Use File was linked to the CMS Physician Compare (PC) database by physician NPI to identify and sum all treatment delivery charges submitted by individual radiation oncologists in the non-facility-based (NFB) setting in 2016. Multivariable logistic regression analysis was carried out to determine provider characteristics (gender, practice rurality, practice region, and years since graduation) that predicted for the delivery of 3D conformal RT (3DCRT), intensity modulated RT (IMRT), stereotactic body RT (SBRT), stereotactic radiosurgery (SRS), low dose rate (LDR) brachytherapy, and high dose rate (HDR) brachytherapy delivery in the Medicare patient population. The overall significance of categorical variables in the multivariable logistic regression model was assessed by the likelihood ratio test (LRT).ResultsIn total, 1,802 physicians from the NFB practice setting were analyzed. Male gender predicted for greater LDR brachytherapy delivery (OR 8.19, 95% CI 2.58-26.05, p

BACKGROUND: Centrally located lung tumors present treatment challenges given their proximity to mediastinal structures including the central airway, esophagus, major vessels, and heart. Therapeutic options can be limited for medically inoperable patients, particularly if they have received previous thoracic radiotherapy. High dose rate (HDR) brachyablation was developed to improve the therapeutic ratio for patients with central lung tumors. The purpose of this study is to report initial safety and efficacy outcomes with this treatment for central lung malignancies. METHODS: From September 2015 to August 2019, a total of 25 patients with 37 pulmonary tumors were treated with percutaneous HDR brachyablation. Treatment was delivered by a multi-disciplinary team of interventional radiologists, pulmonologists, and radiation oncologists. Twenty-three patients received a median dose of 21.5 Gy (range 15-27.5) in a single fraction, whereas two patients received median dose of 24.75 Gy (range 24-25.5) over 2-3 fractions. Tumor local control (LC) was evaluated by Response Evaluation Criteria in Solid Tumors v1.1. Treatment-related toxicities were graded by Common Terminology Criteria for Adverse Events v5.0, with adverse events less than 90 days defined as acute, and those occurring later were defined as late. LC, progression-free survival (PFS), and overall survival (OS) rates were estimated by the Kaplan-Meier method. RESULTS: Of 37 treated tumors, 88% were metastatic. Tumor location was central and ultra-central in 24.3% and 54.1%, respectively. Average tumor volume was 11.6 cm3 (SD 12.4, range 0.57-62.8). Median follow-up was 19 months (range 3-48). Two-year LC, PFS, and OS were 96.2%, 29.7%, and 65.5%, respectively. Thirteen of 39 (33.3%) catheter implantation procedures were associated with trace minor pneumothorax requiring no intervention, 1 (2.5%) procedure with minor radiographic pulmonary hemorrhage, and 4 (10.3%) with major pneumothorax requiring chest tube insertions. All procedural complications resolved within 24 h from treatment. Acute grade 1-2 toxicity was identified in 4 patients, whereas none developed late toxicity beyond 90 days of follow-up. CONCLUSION: Percutaneous HDR brachyablation is a safe and promising treatment option for centrally located primary and metastatic lung tumors. Future comparisons with stereotactic body radiotherapy and other ablative techniques are warranted to expand multi-disciplinary management options.

PURPOSE: To evaluate geometric variations of patients receiving stereotactic body radiotherapy (SBRT) after radical prostatectomy and the dosimetric benefits of stereotactic MRI guided adaptive radiotherapy (SMART) to compensate for these variations. MATERIALS/METHODS: The CTV and OAR were contoured on 55 MRI setup scans of 11 patients treated with an MR-LINAC and enrolled in a phase II trial of post-prostatectomy SBRT. All patients followed institutional bladder and rectum preparation protocols and received five fractions of 6-6.8 Gy to the prostate bed. Interfractional changes in volume were calculated and shape deformation was quantified by the Dice similar coefficient (DSC). Changes in CTV-V95%, bladder and rectum maximum dose, V32.5Gy and V27.5Gy were predicted by recalculating the initial plan on daily MRI. SMART was retrospectively simulated if the predicted dose exceeded pre-set criteria. RESULTS: The CTV volume and shape remained stable with a median volumetric change of 3.0% (IQR -3.0% to 11.5%) and DSC of 0.83 (IQR 0.79 to 0.88). Relatively large volumetric changes in bladder (median -24.5%, IQR -34.6% to 14.5%) and rectum (median 5.4%, IQR - 9.7% to 20.7%) were observed while shape changes were moderate (median DSC of 0.79 and 0.73, respectively). The median CTV-V95% was 98.4% (IQR 94.9% to 99.6%) for the predicted doses. However, SMART would have been deemed beneficial for 78.2% of the 55 fractions based on target undercoverage (16.4%), exceeding OAR constraints (50.9%), or both (10.9%). Simulated SMART improved the dosimetry and met dosimetric criteria in all fractions. Moderate correlations were observed between the CTV-V95% and target DSC (R2 = 0.73) and bladder mean dose versus volumetric changes (R2 = 0.61). CONCLUSIONS: Interfractional dosimetric variations resulting from anatomic deformation are commonly encountered with post-prostatectomy RT and can be mitigated with SMART.

Few studies have examined the cardiac volume and radiation dose differences among cardiac phases during radiation therapy (RT). Such information is crucial to dose reconstruction and understanding of RT related cardiac toxicity. In a cohort of nine patients, we studied the changes in the volume and doses of several cardiac substructures between the end-diastolic and end-systolic phases based on the clinical magnetic resonance-guided RT (MRgRT) treatment plans. Significant differences in the volume and dose between the two phases were observed. Onboard cardiac cine MRI holds promise for patient-specific cardiac sparing treatment designs.

PURPOSE: Stereotactic body radiotherapy (SBRT) in the post-prostatectomy setting is investigational. A major concern is the deformable prostate bed clinical target volume (CTV) and the closely juxtaposed organs-at-risk (OARs). We report a volumetric and dosimetric analysis of kilovoltage cone-beam CT (CBCT) data from the first 18 patients enrolled on a phase II trial of post-prostatectomy SBRT. With instructions on bladder filling and rectal preparation, we hypothesized acceptable CTV coverage while minimal overdosing to OARs could be achieved. METHODS: All patients received 5 fractions of 6-6.8 Gy to the prostate bed. CBCT were taken prior to and halfway through each fraction. CTV and OARs were contoured for each CBCT. Changes in inter- and intra-fraction volume and dose were calculated. Relative changes in CTV V95%, bladder V32.5 Gy, and rectal V32.5 Gy and V27.5 Gy were evaluated. RESULTS: Interfraction CTV volume remained stable, with median change +5.69% (IQR -1.73% to +9.84%). CTV V95% exhibited median change -0.74% (IQR -9.15% to -0.07%). Volumetric and dosimetric changes were minor from interfraction rotation and intrafraction motion. CTV V95% was ≥93% in 13 of 18 (72%) patients; in the remaining five, median change was -14.09% (IQR -16.64% to -13.56%). Interfraction CTV volume change was significantly larger among patients with CTV V95%

Purpose: The purpose of this paper is to explore how preservice teacher's beliefs change over time in a literacy methods elementary licensure course that encourages critical literacy and connects learning. The authors were interested in the interplay among identity, agency and structure within this process and how this connected with other literature on teacher beliefs and technology use. Design/methodology/approach: Utilizing data from a larger ethnographic study and mediated discourse analysis (Scollon and Scollon, 2004), this paper follows preservice teacher's use of digital tools and beliefs about using digital tools in the classroom over a semester-long hybrid course. Findings: Findings show changes in preservice teacher's beliefs about technology use, interest-driven learning and her own agency. These changes were influenced by the framework of the course and course practices. Research limitations/implications: This research study offers practical ways to support preservice teachers' implementation of digital tools with an emphasis on equity. Ultimately, preservice teachers' experience shapes the opportunities students have with digital tools in schools. Practical implications: Recognizing the competing discourses and pressures preservice teachers' experience, the results of this study offer tools to support preservice teachers' agency through the implementation of connected learning principles and critical literacy theories in preservice education courses, leading to the potential to expand equity in school settings. Originality/value: While there is research around connected learning in classrooms, there is limited research on a connected learning framework in preservice education programs. Additionally, this paper brings a new perspective on how pairing an emphasis of equity to a connected learning framework supports teachers' implementation of digital tools.

Despite the benefits of open pedagogy, its use in K-12 schools remains limited. Through this study, the authors examined the lack of open pedagogy usage in schools and potential barriers through the lens of teacher candidates' (n = 29) experiences with open pedagogy assignments. Within this qualitative study, the authors defined open pedagogy and utilized identity building and significance building tools to examine teacher candidates' perceptions of two different open pedagogy assignments. Candidates in one section worked on these assignments in a small group, while candidates in another section worked individually. Notable differences were observed among the candidates' responses that highlight the importance of opportunities for collaborative open pedagogy practices within teacher education programs. This analysis supports the field's understanding of ways teacher candidates' experiences might impact their use of open pedagogy assignments in the future, and, therefore, the advancement of open practices in schools. Implications highlight how open pedagogy in teacher preparation programs have the potential to increase equity-oriented practices in K-12 schools. From this analysis, recommendations are drawn for those who strive to increase equitable learning environments through open practices.

Whole-brain radiation treatment is often considered for patients with leptomeningeal disease. There are limited reports of the development of radiation necrosis after whole-brain radiation treatment and fewer associating the presence of germline mutations with risk. We present a case report to highlight the need for consideration of radiosensitizing mutations when recommending radiation therapy. [ABSTRACT FROM AUTHOR]

Introduction In 2009, the Family Smoking Prevention and Tobacco Control Act prohibited flavored cigarettes but allowed for flavored cigars. Since, there has been a 34% increase in youth cigar use and widened racial disparities. State and local jurisdictions have increasingly enacted flavored tobacco product sales restrictions. As more jurisdictions consider implementing flavor restrictions, it is important to understand their effect on tobacco markets that have high flavor proliferation, including the cigar market. Aims and Methods This study uses data from Truth Initiative's flavor policy database and NielsenIQ retailer scanners for California, Illinois, Massachusetts, and New York. We use a three-way fixed-effect model to assess the impact of the percentage of the population covered by a flavored cigar sales restriction on per capita unit sales of cigars. Results We find that population coverage by cigar sales restrictions was significantly associated with decreases in per capita cigar sales. More specifically, a 25% increase in the percentage of the population covered by a flavored cigar sales restriction was associated with a decrease in per capita all cigar sales of 15%–19%, 4%–10% for large cigars, 17%–21% for cigarillos, and 2%–41% for little cigars. Conclusion Flavored cigar sales restrictions are an effective policy to reduce per capita cigar sales. The Food and Drug Administration (FDA)'s proposed product standards would increase population covered by a flavored cigar sales restriction to 100%, leading to potential significant reductions in cigar sales, especially little cigar, and cigarillo sales. This may also substantially reduce youth cigar use and racial disparities in cigar use. Implications In April 2022, the U.S. FDA published a proposed rule to prohibit characterizing flavors in all cigars and menthol cigarettes. Besides this proposed rule, there has been little federal action to date to reduce sales of flavored cigars. However, as of March 31, 2022, Massachusetts and 333 localities across 10 states have enacted policies that restrict the sale of flavored cigars and other tobacco products. We find that population coverage by cigar sales restrictions is significantly associated with decreases in per capita cigar sales. [ABSTRACT FROM AUTHOR]

Despite the high prevalence and poor outcome of patients with metastatic lung cancer the mechanisms of tumour progression and metastasis remain largely uncharacterized. Here we modelled human lung adenocarcinoma, which frequently harbours activating point mutations in KRAS and inactivation of the p53 pathway, using conditional alleles in mice. Lentiviral-mediated somatic activation of oncogenic Kras and deletion of p53 in the lung epithelial cells of Kras(LSL-G12D/+);p53(flox/flox) mice initiates lung adenocarcinoma development. Although tumours are initiated synchronously by defined genetic alterations, only a subset becomes malignant, indicating that disease progression requires additional alterations. Identification of the lentiviral integration sites allowed us to distinguish metastatic from non-metastatic tumours and determine the gene expression alterations that distinguish these tumour types. Cross-species analysis identified the NK2-related homeobox transcription factor Nkx2-1 (also called Ttf-1 or Titf1) as a candidate suppressor of malignant progression. In this mouse model, Nkx2-1 negativity is pathognomonic of high-grade poorly differentiated tumours. Gain- and loss-of-function experiments in cells derived from metastatic and non-metastatic tumours demonstrated that Nkx2-1 controls tumour differentiation and limits metastatic potential in vivo. Interrogation of Nkx2-1-regulated genes, analysis of tumours at defined developmental stages, and functional complementation experiments indicate that Nkx2-1 constrains tumours in part by repressing the embryonically restricted chromatin regulator Hmga2. Whereas focal amplification of NKX2-1 in a fraction of human lung adenocarcinomas has focused attention on its oncogenic function, our data specifically link Nkx2-1 downregulation to loss of differentiation, enhanced tumour seeding ability and increased metastatic proclivity. Thus, the oncogenic and suppressive functions of Nkx2-1 in the same tumour type substantiate its role as a dual function lineage factor.

This qualitative study examines open pedagogy as a critical instructional strategy in online community college settings to increase opportunities for authentic interactions that support student persistence. Discourse analysis was used to understand how community college students (n=78) perceive and connect with different aspects of open pedagogy activities. The study's findings underscore the students' awareness of their audience in online settings, their value of collaborative efforts to design digital materials, and the significance of acknowledging the digital learning context. Despite many students choosing to share their work publicly, challenges related to sharing work publicly were illuminated across reflective questionnaire responses. To address these issues, the study recommends enhancing media literacy, providing group collaboration options, and emphasizing institutional support. Further research should explore the influence of social media experiences and AI tools on the public sharing of open pedagogy activities. Ultimately, by embracing open pedagogy in online learning contexts while considering individual student identities and perceptions, community college settings can enhance online interactions, engagement, and student persistence. [ABSTRACT FROM AUTHOR]