Glomus jugulotympanicum tumor treated with radiation therapy: A case report with review of literature.

Glomus tumors (or paragangliomas) are rare, benign tumors of neuroendocrine origin that appear in tissues of paraganglionic origin. This clinical entity poses a significant treatment challenge due to its proximity to critical neurovascular structures, thus the potential of morbid functional damage caused by disease progression and/or treatment approach. While surgery remains the standard of care for such cases, there has been an increasing trend toward management with radiotherapy or close observation. Here, we present a case of a large and irregularly shaped glomus jugulotympanicum tumor that was treated with volumetric arc radiotherapy. Given the risk of cranial neuropathy with surgery, radiation was the preferred treatment modality. This case demonstrated the safety and efficacy of volumetric arc radiotherapy in the management of a large glomus tumor with a complex shape.

Bundling Colorectal Cancer Screening Outreach with Screening for Social Risk in Federally Qualified Health Centers: A Stepped-Wedge Implementation-Effectiveness Study.

BACKGROUND: Bundling is combining individual interventions to meet quality metrics. Bundling offers of cancer screening with screening for social determinants of health (SDOH) may enable health centers to assist patients with social risks and yield efficiencies. OBJECTIVE: To measure effects of bundling fecal immunochemical testing (FIT) and SDOH screening in federally qualified health centers (FQHCs). DESIGN: Clustered stepped-wedge trial. PARTICIPANTS: Four Massachusetts FQHCs randomized to implement bundled FIT-SDOH over 8-week "steps." INTERVENTION: Outreach to 50-75-year-olds overdue for CRC screening to offer FIT with SDOH screening. The implementation strategy used facilitation and training for data monitoring and reporting. MAIN MEASURES: Implementation process descriptions, data from facilitation meetings, and CRC and SDOH screening rates. Rates were compared between implementation and control FQHCs in each "step" by fitting generalized linear mixed-effects models with random intercepts for FQHCs, patients, and "step" by FQHC. KEY RESULTS: FQHCs tailored implementation processes to their infrastructure, workflows, and staffing and prioritized different groups for outreach. Two FQHCs used population health outreach, and two integrated FIT-SDOH within established programs, such as pre-visit planning. Of 34,588 patients overdue for CRC screening, 54% were female; 20% Black, 11% Latino, 10% Asian, and 47% white; 32% had Medicaid, 16% Medicare, 32% private insurance, and 11% uninsured. Odds of CRC screening completion in implementation "steps" compared to controls were higher overall and among groups prioritized for outreach (overall: adjusted odds ratio (aOR) 2.41, p = 0.005; prioritized: aOR 2.88, p = 0.002). Odds of SDOH screening did not differ across "steps." CONCLUSIONS: As healthcare systems are required to conduct more screenings, it is notable that outreach for a long-standing cancer screening requirement increased screening, even when bundled with a newer screening requirement. This outreach was feasible in a real-world safety-net clinical population and may conserve resources, especially compared to more complex or intensive outreach strategies. CLINICAL TRIALS REGISTRATION: NCT04585919.

Implications of siRNA Therapy in Bone Health: Silencing Communicates.

The global statistics of bone disorders, skeletal defects, and fractures are frightening. Several therapeutic strategies are being used to fix them; however, RNAi-based siRNA therapy is starting to prove to be a promising approach for the prevention of bone disorders because of its advanced capabilities to deliver siRNA or siRNA drug conjugate to the target tissue. Despite its 'bench-to-bedside' usefulness and approval by food and drug administration for five siRNA-based therapeutic medicines: Patisiran, Vutrisiran, Inclisiran, Lumasiran, and Givosiran, its use for the other diseases still remains to be resolved. By correcting the complications and complexities involved in siRNA delivery for its sustained release, better absorption, and toxicity-free activity, siRNA therapy can be harnessed as an experimental tool for the prevention of complex and undruggable diseases with a personalized medicine approach. The present review summarizes the findings of notable research to address the implications of siRNA in bone health for the restoration of bone mass, recovery of bone loss, and recuperation of bone fractures.

Leveraging an implementation science partnership network to understand how Federally Qualified Health Centers operationalize and address health equity.

Health equity-focused implementation research requires using definitions and approaches that are relevant and meaningful to implementation partners. We examined how health equity was operationalized and addressed at Federally Qualified Health Centers (FQHCs). We conducted semi-structured interviews with leadership (n = 19) and staff (n = 12) at 10 FQHCs in an implementation science partnership network for cancer control equity to understand how they operationalized and addressed health equity. We performed rapid qualitative analysis and shared findings with a larger group of 13 community health centers (including the 10 FQHCs) at an Implementation Learning Community (ILC) to identify action areas for research and practice, followed by a second phase of synthesizing qualitative codes into themes and mapping themes onto a framework for advancing health equity in healthcare organizations. Participants defined health equity as central to the mission of FQHCs, and identified barriers (e.g. financing models) and facilitators (e.g. interpreter services) to advancing health equity at FQHCs. These findings resonated with ILC participants who emphasized the challenge of addressing root cause social determinants of inequities using limited available resources in FQHCs and the importance of developing meaningful collaboration with communities for data collection, data interpretation, data use, and data ownership. Themes captured recommendations to advance health equity in daily work at FQHCs, including investments in staffing, training, and resources. Mapping qualitative themes from health equity-centered interviews with FQHC partners onto a framework for advancing health equity in healthcare organizations can provide clear, context-specific direction for actions aimed at improving health and healthcare equity.

Health equity-focused implementation research requires using definitions and approaches that are relevant and meaningful to implementation partners. Toward this goal, our research team asked leadership and staff at Federally Qualified Health Centers (FQHCs) to share how they defined and addressed health equity at their practice settings. FQHC participants defined health equity as the essential mission of FQHCs as safety net organizations delivering care to medically underserved populations. In addition, key informants identified barriers (e.g. financing models) and facilitators (e.g. interpreter services) to advancing health equity at FQHCs. We presented these findings to a larger group of FQHC stakeholders who recommended that future implementation research and practice consider how FQHCs are challenged to address the root causes of healthcare inequities with limited resources. They also highlighted the importance of meaningful collaboration among researchers, FQHCs, and communities for data collection, data interpretation, data use, and data ownership to advance health equity. Conducting research to understand the perspectives and experiences of FQHC partners can provide clear, context-specific direction for actions to improve health equity and can inform future approaches to health equity-focused implementation research that ismeaningful to FQHC partners and the communities they serve.

Challenges and recommendations for measuring time devoted to implementation and intervention activities in health equity-focused, resource-constrained settings: a qualitative analysis.

BACKGROUND: There is little guidance for conducting health equity-focused economic evaluations of evidence-based practices in resource-constrained settings, particularly with respect to staff time use. Investigators must balance the need for low-touch, non-disruptive cost data collection with the need for data on providing services to priority subpopulations. METHODS: This investigation took place within a pilot study examining the implementation of a bundled screening intervention combining screening for social determinants of health and colorectal cancer at four federally qualified health centers (FQHCs) in the Boston metropolitan area. Methods for collecting data on personnel costs for implementation and intervention activities, including passive (automatic) and active (non-automatic, requiring staff time and effort) data collection, as well as three alternate wordings for self-reporting time-use, were evaluated qualitatively using data collected through interviews with FQHC staff (including clinicians, population health staff, and community health workers) and assessments of data completeness. RESULTS: Passive data collection methods were simple to execute and resulted in no missing data, but missed implementation and intervention activities that took place outside planned meetings. Active cost data collection using spreadsheets was simple for users when applied to care processes already tracked in this fashion and yielded accurate time use data. However, for tasks where this was not typical, and when tasks were broken up over multiple sessions, spreadsheets were more challenging to use. Questions asking about time use for a typical rather than specific time period, and for typical patients, yielded the most reliable and actionable data. Still, even the best-performing question had substantial variability in time use estimates. Participants noted that patient characteristics of interest for equity-focused research, including language spoken, adverse social determinants of health, and issues related to poverty or mental health, all contributed significantly to this variability. CONCLUSIONS: Passively collected time use data are the least burdensome and should be pursued in research efforts when possible, but should be accompanied by qualitative assessments to ensure the data are an accurate reflection of effort. When workflows are already tracked by active data collection, these are also strong data collection methods. Self-reported time use will be most accurate when questions inquire about "typical" tasks and specific types of patients.

Stroke death in patients receiving radiation for head and neck cancer in the modern era.

Objectives: Head and neck cancer is a common malignancy frequently treated with chemotherapy and radiotherapy. Studies have shown an increased risk of stroke with the receipt of radiotherapy, but data on stroke-related mortality are limited, particularly in the modern era. Evaluating stroke mortality related to radiotherapy is vital given the curative nature of head and neck cancer treatment and the need to understand the risk of severe stroke in this population. Methods: We analyzed the risk of stroke death among 122,362 patients (83,651 patients who received radiation and 38,711 patients who did not) with squamous cell carcinoma of the head and neck (HNSCC) diagnosed between 1973 and 2015 in the SEER database. Patients in radiation vs. no radiation groups were matched using propensity scores. Our primary hypothesis was that radiotherapy would increase the hazard of death from stroke. We also examined other factors impacting the hazard of stroke death, including whether radiotherapy was performed during the modern era when IMRT and modern stroke care were available as well as increased HPV-mediated cancers of the head and neck. We hypothesized that the hazard of stroke death would be less in the modern era. Results: There was an increased hazard of stroke-related death in the group receiving radiation therapy (HR 1.203, p = 0.006); however, this was a very small absolute increase, and the cumulative incidence function of stroke death was significantly reduced in the modern era (p < 0.001), cohorts with chemotherapy (p=0.003), males (p=0.002), younger cohorts (p<0.001) and subsites other than nasopharynx (p=0.025). Conclusions: While radiotherapy for head and neck cancer increases the hazard of stroke death, this is reduced in the modern era and remains a very small absolute risk.

Sphenoid Sinus Aspergilloma in an Immunocompetent and an Immunocompromised Patient: A Case Report.

Sellar, supra-sellar aspergilloma are rare differentials for a sellar mass. CNS aspergilloma occurs due to intracranial extension of invasive fungal sinusitis, and often first manifests with symptoms of headache and visual disturbance. This complication is much more common in immunocompromised patients, but proliferation of fungal pathogens and low index for suspicion has led to more severe breakthrough cases in the immunocompetent. If treated timely, these CNS lesions can have a relatively good prognosis. Conversely, delays in diagnosis can confer very high rates of mortality among patients with invasive fungal disease. Originally from India, in this case report, we describe two patients presenting with sellar, supra-sellar tumors, who eventually were diagnosed with confirmed cases of invasive intracranial aspergilloma. We describe the clinical presentation, imaging techniques, and treatment modalities for this relatively rare disease in both the immunocompromised and the immunocompetent.

Early-Stage Primary Lung Neuroendocrine Tumors Treated With Stereotactic Body Radiation Therapy: A Multi-Institution Experience.

PURPOSE: Current guidelines recommend surgery as standard of care for primary lung neuroendocrine tumor (LNET). Given that LNET is a rare clinical entity, there is a lack of literature regarding treatment of LNET with stereotactic body radiation therapy (SBRT). We hypothesized that SBRT could lead to effective locoregional tumor control and long-term outcomes. METHODS AND MATERIALS: We retrospectively reviewed 48 tumors in 46 patients from 11 institutions with a histologically confirmed diagnosis of LNET, treated with primary radiation therapy. Data were collected for patients treated nonoperatively with primary radiation therapy between 2006 and 2020. Patient records were reviewed for lesion characteristics and clinical risk factors. Kaplan-Meier analysis, log-rank tests, and Cox multivariate models were used to compare outcomes. RESULTS: Median age at treatment was 71 years and mean tumor size was 2 cm. Thirty-two lesions were typical carcinoid histology, 7 were atypical, and 9 were indeterminate. The most common SBRT fractionation schedule was 50 to 60 Gy in 5 daily fractions. Overall survival at 3, 6, and 9 years was 64%, 43%, and 26%, respectively. Progression-free survival at 3, 6, and 9 years was 88%, 78%, and 78%, respectively. Local control at 3, 6, and 9 years was 97%, 91%, and 91%, respectively. There was 1 regional recurrence in a paraesophageal lymph node. No grade 3 or higher toxicity was identified. CONCLUSIONS: This is the largest series evaluating outcomes in patients with LNET treated with SBRT. This treatment is well tolerated, provides excellent locoregional control, and should be offered as an alternative to surgical resection for patients with early-stage LNET, particularly those who may not be ideal surgical candidates.

Stakeholder and Equity Data-Driven Implementation: a Mixed Methods Pilot Feasibility Study.

We conducted a mixed methods pilot feasibility study of a Stakeholder and Equity Data-Driven Implementation (SEDDI) process to facilitate using healthcare data to identify patient groups experiencing gaps in the use of evidence-based interventions (EBIs) and rapidly adapt EBIs to achieve greater access and equitable outcomes. We evaluated the feasibility and acceptability of SEDDI in a pilot hybrid type 2 effectiveness-implementation trial of a paired colorectal cancer (CRC) and social needs screening intervention at four federally qualified community health centers (CHCs). An external facilitator partnered with CHC teams to support initial implementation, followed by the SEDDI phase focused on advancing health equity. Facilitation sessions were delivered over 8 months. Preliminary evaluation of SEDDI involved convergent mixed methods with quantitative survey and focus group data. CHCs used data to identify gaps in outreach and completion of CRC screening with respect to race/ethnicity, gender, age, and language. Adaptations to improve access and use of the intervention included cultural, linguistic, and health literacy tailoring. CHC teams reported that facilitation and systematic review of data were helpful in identifying and prioritizing gaps. None of the four CHCs completed rapid cycle testing of adaptations largely due to competing priorities during the COVID-19 response. SEDDI has the potential for advancing chronic disease prevention and management by providing a stakeholder and data-driven approach to identify and prioritize health equity targets and guide adaptations to improve health equity. ClinicalTrials.gov Identifier: NCT04585919.

Patterns of recurrence after intracranial stereotactic radiosurgery for brain-only metastases from non-small cell lung cancer and the impact of upfront thoracic therapy with synchronous presentation.

Background: We characterized long-term organ-specific patterns of recurrence, time to progression (TTP) and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) with brain-only metastases treated with single-fraction stereotactic radiosurgery (SRS) and analyzed the impact of upfront thoracic therapy (UTT) in those with synchronous presentation of primary NSCLC and brain metastases. Methods: The clinical records of 137 patients with brain metastases from NSCLC treated with intracranial SRS, and no other metastatic sites, were retrospectively reviewed. Patients with available follow-up imaging (n=124) were analyzed for patterns of recurrence; all were analyzed for OS. Results: The majority of first distant recurrences were in brain and thoracic sites, while extra-thoracic sites were relatively uncommon. After median follow-up of 16.0 months, 24.8% did not develop recurrence outside of brain and/or thoracic sites and 43.5% were free of distant extracranial recurrence. Whole brain radiotherapy (WBRT) and UTT, but not systemic therapy, altered patterns of recurrence and intracranial or extracranial TTP. Multivariable analysis revealed UTT, but not systemic therapy or WBRT, was associated with more favorable OS [hazard ratio (HR) 0.515, P=0.029] among 88 patients with synchronous presentation. Within the subgroup of thoracic stage III patients (n=69), those treated with UTT experienced remarkable median extracranial TTP and OS of 19.3 and 22.7 months, respectively. Conclusions: First and cumulative recurrences in patients treated with intracranial SRS for NSCLC metastases limited to brain are most often in the brain and thorax. Long-term survival is possible, regardless of thoracic stage, and is dependent on UTT among other factors.

Oligoprogression in non-small cell lung cancer: a narrative review.

Background and Objective: Non-small cell lung cancer (NSCLC) accounts for 80% of lung cancers and is the most common non-cutaneous cancer world-wide. In NSCLC, oligometastatic and oligoprogressive disease (OPD) have been recognized as separate entities within the realm of metastatic disease and are emerging concepts in the context of targeted systemic therapies. Our objectives are to discuss the current literature regarding the evolving definitions of OPD in the context of oligometastatic disease (OMD) for NSCLC. Further, to discuss current and future clinical trials that have shaped our local approach with stereotactic body radiation therapy (SBRT)/stereotactic ablative radiotherapy (SABR). Methods: Literature on OPD in NSCLC and local ablative therapy (LAT) including SBRT/SABR and stereotactic radiosurgery (SRS) was reviewed. Key Content and Findings: Oligoprogression is defined as limited (usually 3-5) metastatic areas progressing while on/off systemic therapy in the background of oligometastatic or polymetastatic disease. Prognosis in OPD with treatment (such as LAT and systemic therapy) may be more favorable. Outcomes for patients progressing on tyrosine kinase inhibitors (TKIs) with molecular mutations [such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK)] who receive LAT are promising. Conclusions: Patients presenting with NSCLC metastasis with progression at a limited number of sites on/off a given line of systemic therapy may have favorable outcomes with aggressive LAT, which includes SBRT/SABR/SRS. Further studies need to be completed to further optimize treatment recommendations.

New dosimetric guidelines for linear Boltzmann transport equations through comparative evaluation of stereotactic body radiation therapy for lung treatment planning.

PURPOSE: To propose guidelines for lung stereotactic body radiation therapy (SBRT) when using Acuros XB (AXB) equivalent to the existing ones developed for convolution algorithms such as analytic anisotropic algorithm (AAA), considering the difference between the algorithms. METHODS: A retrospective analysis was performed on 30 lung patients previously treated with SBRT. The original AAA plans, which were developed using dynamic conformal arcs, were recalculated and then renormalized for planning target volume (PTV) coverage using AXB. The recalculated and renormalized plans were compared to the original plans based on V100% and V90% PTV coverage, as well as V105%, conformality index, D2cm , Rx/Dmax , R50, and Dmin . These metrics were analyzed nominally and on variations according to RTOG and NRG guidelines. Based on the relative difference between each metric in the AAA and AXB plans, new guidelines were developed. The relative differences in our cohort were compared to previously documented AAA to AXB comparisons found in the literature. RESULTS: AAA plans recalculated in AXB had a significant reduction in most dosimetric metrics. The most notable changes were in V100% (4%) and the conformality index (7.5%). To achieve equal PTV coverage, AXB required an average of 1.8% more monitor units (MU). This fits well with previously published data. Applying the new guidelines to the AXB plans significantly increased the number of minor violations with no change in major violations, making them comparable to those of the original AAA plans. CONCLUSION: The relative difference found between AAA and AXB for SBRT lung plans has been shown to be consistent with previous works. Based on these findings, new guidelines for lung SBRT are recommended when planning with AXB.

Radiologically Occult Lung Cancer Curatively Treated with High-Dose Rate Endobronchial Brachytherapy.

Most patients diagnosed with early-stage non-small cell lung cancer (NSCLC) can be easily cured with surgery or stereotactic body radiotherapy (SBRT). Modalities such as photodynamic therapy, cryotherapy, or laser therapy only offer temporary palliation. A 79-year-old gentleman with early-stage NSCLC who underwent a left lower lobe lobectomy in 2009 presented to us again in 2010 with hemoptysis. A friable ~5 cm tumor along the bifurcation of anterior and the posterior segment of the right upper lobe was noted on bronchoscopic examination, and biopsy confirmed this to be squamous cell carcinoma. Because of his previous surgery, the patient was not a candidate for another surgery. SBRT was not possible as the lesion could not be seen on radiologic imaging. The patient was, therefore, treated with curative intent high-dose rate endobronchial brachytherapy (HDR-EBBT) in 4 weekly sessions of 7 Gy per fraction delivered at a depth of 8 mm, covering ~5 cm tumor plus 1 cm margin proximally and distally. He tolerated the treatment well without any acute or late side effects and was followed every 3 months thereafter with bronchoscopy examinations for 6 months and subsequently with computerized tomography (CT) imaging. In July 2018, the patient started having episodes of hemoptysis and evaluation leads to diagnosis of a third primary lung cancer, which was successfully treated with SBRT with image-guided radiotherapy using a five-fraction regimen. The patient's most recent CT from July 2019 showed no evidence of disease. We conclude that in patients with early-stage NSCLC, when surgery or SBRT is not feasible due to radiologic occult nature, HDR-EBBT can yield excellent long-term outcome.

Squamous cell carcinoma of the head and neck with unknown primary: trends and outcomes from a hospital-based registry.

BACKGROUND: Squamous cell carcinoma of unknown primary of the head and neck region is a known entity described mainly by retrospective reports. We searched a hospital-based registry to better describe the changing incidence, and to assess diagnostic and treatment strategies. METHODS: The National Comprehensive Cancer Database was queried for head and neck cancers from oropharynx, tonsil, tongue, larynx, hypopharynx primary sites with a designation of clinical T0, representing an unknown primary. Kaplan Meier, Cox multivariate models, and propensity matched cohorts were used to assess significant factors for overall survival. RESULTS: There were 964 cases that met the criteria, and 468 cases with known treatments, staging, and survival data. The incidence increased over time, with the highest rates supported in the last 5 years. In patients who underwent HPV testing, 72% were positive. Patients with AJCC 7th clinical N2c or N3 disease had significantly worse outcomes despite the majority receiving neck dissection, radiation, and chemotherapy. Local surgery, compared to incisional or excisional biopsy, had the highest diagnostic yield of finding a primary tumor. In multivariate models, no combination of surgical approach, radiation, or systemic therapy was significantly associated with improved survival. This remained true in 1:1 propensity matched cohorts for age, comorbidities, and clinical nodal burden. In a subset of cN1 patients, combined chemoradiation therapy after excisional biopsy or local surgery was associated with (not statistically significant) improved survival compared to radiation alone (P=0.054). CONCLUSIONS: The incidence of unknown primary head and neck carcinoma is increasing, and current cases have a high proportion of HPV positivity. HPV positivity predicts strongly for a tonsil primary. Local surgery was associated with the highest diagnostic yield. Clinical nodal burden strongly predicts for overall outcome, and type of treatment facility is an important driver of survival. A subset of cN1 patients may benefit from the addition of chemotherapy to radiation.

Second Primary Non-Small-Cell Lung Cancer After Head and Neck Cancer: A Population-Based Study of Clinical and Pathologic Characteristics and Survival Outcomes in 3597 Patients.

INTRODUCTION: Retrospective studies have shown an increased risk of second primary lung cancer in patients with a history of head and neck cancer (HNC). No population-based study has examined the overall survival (OS) outcomes of patients with second primary non-small-cell lung cancer (NSCLC) after HNC comparison with patients with first primary NSCLC. PATIENTS AND METHODS: Individuals with histologically confirmed NSCLC diagnosed after nonmetastatic squamous-cell carcinoma of the head and neck (HNC-NSCLC; n = 3597) were identified in Surveillance, Epidemiology, and End Results 18 registries (1988-2013). OS and baseline characteristics were compared in patients with first primary NSCLC (NSCLC-1; n = 365,551) in the same registries. RESULTS: Squamous NSCLC was more common in HNC-NSCLC (n = 745 [64.1%] localized, n = 833 [71.9%] regional, and n = 811 [63.5%] distant) than in the NSCLC-1 (n = 30,901 [38.3%] localized, n = 50,557 [48.2%] regional, and n = 53,720 [29.8%] distant; P < .001). The leading cause of death in HNC-NSCLC was NSCLC (n = 2183; 60.6%), and median OS after localized, regional, and distant NSCLC diagnosis was 2.50 years, 1.17 years, and 5 months, respectively. For NSCLC-1, median OS was 4.58 years, 1.58 years, and 6 months, respectively. These differences were significant (P < .001). In multivariable analysis, a history of HNC remained associated with worse OS for localized (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.29-1.51; P < .001), regional (HR, 1.26; 95% CI, 1.19-1.35; P < .001) and distant (HR, 1.11; 95% CI, 1.04-1.18; P < .01) stage NSCLC. CONCLUSION: A history of HNC adversely affects OS in patients who subsequently develop NSCLC. This OS decrement might have implications for NSCLC surveillance and NSCLC therapy selection in this population.

Stereotactic body radiotherapy in patients with multiple lung tumors: a focus on lung dosimetric constraints.

Introduction: Lung dosimetric constraints with stereotactic body/ablative radiotherapy (SBRT/SABR) for multiple lung lesions are not well-characterized in published literature. Classically, the lung is considered a 'parallel' organ, for which injury to functional subunits could result in partially compromised function of that organ/tissue. Therefore, with SBRT/SABR for >1 thoracic target (especially involving both lungs), lung dosimetry requires special consideration.Areas covered: Current cooperative group and multi-institutional studies of SBRT/SABR for oligometastases rely on lung constraints from expert opinion, including constraints of exposure (i.e., volume of lung receiving more than a threshold dose or mean lung dose) and/or critical volume (i.e. volume of lung receiving less than a threshold dose; also termed complementary volume). For radiation pneumonitis, which reflects inflammatory lung injury, it remains unclear which type of constraint is more predictive of toxicity risks.Expert opinion: With SBRT/SABR for multiple lung lesions, it is prudent to use both exposure and critical volume constraints. Treatment on alternate days (for radiation plans with separate treatment fields) or staging treatment may also lower lung toxicity risks. Further study on lung normal tissue complication probability in the setting of multiple lung targets is urgently needed, particularly analyses of critical volume metrics, which are relatively poorly studied.

Hypofractionated Stereotactic Radiotherapy for Non-breast or Prostate Cancer Oligometastases: A Tail of Survival Beyond 10 Years.

Purpose and Objective(s): We sought to analyze the long-term follow-up of patients treated with hypofractionated, stereotactic radiotherapy (HSRT) for oligometastases from malignancies other than breast or prostate cancer. Materials and Methods: From 2001 to 2006, 82 cancer patients with 1-5 radiographically apparent metastatic lesions (in 1-3 organs) from primary sites other than breast or prostate cancer, were enrolled on a prospective study of HSRT. Freedom from widespread metastasis (FFWM) was defined from date of enrollment until death, an event (i.e., widespread distant metastasis not amenable to local therapy), or last radiographic study. Local recurrence was scored as an event if pathologically confirmed or if a treated lesion increased by ≥20% using RECIST criteria. Prognostic variables were assessed using Cox regression analysis. Results: The mean age was 61 ± 11 years, with a male to female ratio of 46:36. The most common metastatic sites were liver (50%), lung (48%), thoracic lymph nodes (18%), and bone (5%). Sixty-one patients (74%) had 1 involved organ and 18 (22%) had 1 lesion treated. The preferred dose-fractionation scheduled was 50 Gy in 10 fractions (52 patients). The median follow-up was 1.7 years. Eleven patients lived >5 years, and 6 lived >10 years. The 5-year OS, PFS, FFWM, and LC rates were 13.4, 7.3, 18.3, and 63.4%, and the 10-years OS, PFS, FFWM, and patient LC rates were 7.3, 6.1, 13.4, and 62.2%, respectively. A greater net gross tumor volume (GTV) was significantly adverse for OS (p < 0.01) and LC (p < 0.01). For FFWM, net GTV was not a significant factor (p = 0.14). Four patients remain alive at >13 years from enrollment and treatment, without evidence of active disease. Conclusion: A small subset of select non-breast, non-prostate cancer patients with limited metastasis treated with HSRT are long-term survivors. Net GTV is a significant factor for tumor control and survival. Further research is needed to help better select patients most likely to benefit from local therapy for metastatic disease.

Inoperable Pulmonary Carcinoid Tumors: Local Control Rates With Stereotactic Body Radiotherapy/Hypofractionated RT With Image-Guided Radiotherapy.

INTRODUCTION: Surgery is the standard of care for pulmonary carcinoid tumors; however, options for inoperable patients are few. We report the outcomes of inoperable pulmonary carcinoid patients treated with stereotactic body radiotherapy (SBRT). PATIENTS AND METHODS: From an institutional database, we retrospectively identified patients treated with SBRT for pulmonary carcinoid tumors from 2007 to 2017. Additional inclusion criteria were previous histopathologic diagnosis, age older than 18 years and Karnofsky performance status ≥ 70. RESULTS: Ten patients were treated for 12 pulmonary carcinoid lesions with 5 to 10 fractions of SBRT. Their median age was 66.5 years (range, 40-83 years) and most presented with nonspecific symptoms of cough, shortness of breath, or hemoptysis. Pathology revealed typical carcinoid for 9 patients, with the 10th with atypical histology. The median prescription dose for all patients was 50 Gy in 5 to 10 fractions (range, 40-60 Gy) with SBRT/hypofractionated radiation with daily image-guided radiotherapy (IGRT) delivered using a linear accelerator with respiratory monitoring. Four patients received 10-fraction hypofractionated radiation with daily IGRT and 6 others received 5-fraction SBRT. The follow-up after SBRT/hypofractionated IGRT ranged from 6 to 56 months (median, 25 months). Four patients were alive with stable disease at their last follow-up. Two patients died from disease progression in the mediastinal lymph nodes as well as in the lung. Both opted for palliative treatment. The other 4 patients died from their comorbid medical conditions, but had stable disease at their last follow-up. Median overall survival was 27.1 months (range, 5.5-56 months). CONCLUSION: Pulmonary carcinoid tumors treated with SBRT have a promising tumor control rate and survival.

Characterization of the ventricular-subventricular stem cell niche during human brain development.

Human brain development proceeds via a sequentially transforming stem cell population in the ventricular-subventricular zone (V-SVZ). An essential, but understudied, contributor to V-SVZ stem cell niche health is the multi-ciliated ependymal epithelium, which replaces stem cells at the ventricular surface during development. However, reorganization of the V-SVZ stem cell niche and its relationship to ependymogenesis has not been characterized in the human brain. Based on comprehensive comparative spatiotemporal analyses of cytoarchitectural changes along the mouse and human ventricle surface, we uncovered a distinctive stem cell retention pattern in humans as ependymal cells populate the surface of the ventricle in an occipital-to-frontal wave. During perinatal development, ventricle-contacting stem cells are reduced. By 7 months few stem cells are detected, paralleling the decline in neurogenesis. In adolescence and adulthood, stem cells and neurogenesis are not observed along the lateral wall. Volume, surface area and curvature of the lateral ventricles all significantly change during fetal development but stabilize after 1 year, corresponding with the wave of ependymogenesis and stem cell reduction. These findings reveal normal human V-SVZ development, highlighting the consequences of disease pathologies such as congenital hydrocephalus.

Comparison of Single- and Five-fraction Regimens of Stereotactic Body Radiation Therapy for Peripheral Early-stage Non-small-cell Lung Cancer: A Two-institution Propensity-matched Analysis.

PURPOSE: To evaluate differences in local control (LC), disease-specific (DC), and overall survival (OS) of patients with early-stage non-small-cell lung cancer (NSCLC) treated with single- (SF) versus 5-fraction (FF) stereotactic body radiation therapy (SBRT) at 2 institutions. PATIENTS AND METHODS: Peripheral early-stage NSCLC cases treated with a median dose of 30 Gy in SF or a median dose of 50 Gy in FF were included per institutional practice. Kaplan-Meier and Cox models were used to assess survival. A matched-pair analysis was performed to account for imbalances. Toxicities including Common Terminology Criteria for Adverse Events (CTCAE) grade 3 pneumonitis, chest wall pain requiring long-acting narcotics, and hospitalization for respiratory events 6 months posttreatment were recorded. RESULTS: A total of 163 lesions were treated between 2007 and 2015; 65 received SF SBRT and 98 received FF SBRT. Most tumors were T1 (n = 92) and T2 (n = 34) lesions and had adenocarcinoma (n = 77) and squamous cell carcinoma (n = 46) histologies, respectively. In the matched cohort, there were no differences in OS, LC, DC, or progression-free survival between the groups. LC and OS at 1 year in the matched cohort was 95% and 88%, and 87% and 84% in the SF and FF cohorts, respectively. There was 1 grade 3 pneumonitis in the FF group, and 9 total hospitalizations post-SBRT, 3 (5%) in the SF group and 6 (6%) in the FF group. CONCLUSIONS: No statistically significant differences were seen in LC or DC following SF or FF SBRT in this matched cohort of peripheral lesions. No grade 4 or higher toxicities were reported.