Brachytherapy in children, adolescents, and young adults: An underutilized modality in the United States?

BACKGROUND: Brachytherapy (BT) delivers highly conformal radiation and spares surrounding tissues, which may limit late effects in pediatric, adolescent, and young adult (AYA) patients. We aimed to characterize trends in BT use for this population in the United States, focusing on patients with rhabdomyosarcoma (RMS). METHODS: The National Cancer Database was queried to identify patients ≤ 21 who were treated for solid tumor malignancies in the United States from 2004 to 2016. We obtained disease, treatment, and outcome data for patients treated with BT, in particular for RMS. RESULTS: 99 506 pediatric and AYA patients met study inclusion. Of these, 22 586 (23%) received radiation therapy (external beam radiation therapy [EBRT] and/or BT) and 240 (0.2%) received BT. Among patients treated with BT, 139 (58%) underwent surgery and 58 (24%) received EBRT. A total of 3836 patients were treated for RMS during this period. Of these, 2531 (66%) received any radiation and 37 (1%) received BT (EBRT + BT in 3, BT in 34). Of patients treated with BT for RMS, 28 (76%) underwent surgery + BT. Survival data were available for 31 patients treated with BT for RMS. With a median follow-up of 63 months, overall survival was 100% for patients with RMS of a favorable site treated with BT. CONCLUSIONS: BT is rarely used to treat pediatric and AYA patients in the United States. Patients treated with BT for RMS experienced favorable survival, suggesting that this approach may not compromise oncologic outcomes and warrants further study as a therapeutic option in pediatric and AYA patients, specifically in RMS.

Prostate Cancer in Older Adults: Risk of Clinically Meaningful Disease, the Role of Screening and Special Considerations.

PURPOSE OF REVIEW: Prostate cancer is the second most common cancer in men in the USA and several studies suggest more aggressive disease in older patients. However, screening remains controversial, especially in the older patient population. RECENT FINDINGS: Aggressive prostate cancers are more common in older men. Screening trial results are conflicting but data suggest an improvement in prostate cancer mortality and increased detection of metastatic disease with screening. When PSA is utilized with multiparametric MRI and biomarker assays, patients at significant risk of clinically meaningful prostate cancer can be appropriately selected for biopsy. A thoughtful and individualized approach is central when considering prostate cancer screening in older men. This approach includes life expectancy estimation, use of appropriate geriatric assessment tools, use of multiparametric MRI and biomarkers in addition to PSA, and most importantly shared decision-making with patients.

Evolving trends in the management of high-intermediate risk endometrial cancer in the United States.

OBJECTIVE: Gynecologic oncology group protocol 249 (GOG 249) is the contemporary US study that aimed to define the standard of care adjuvant therapy for patients with high-intermediate risk (HIR) endometrial cancer; patients were randomized to pelvic radiation therapy (RT) or vaginal brachytherapy (VBT) with chemotherapy (VBT-C). The preliminary results of GOG 249 were recently presented, yet the management of patients represented in this trial remains controversial. We set out to review US patterns of care for patients meeting eligibility criteria for GOG 249. METHODS: The National Cancer Database (NCDB) was used to identify patients meeting GOG 249 eligibility criteria between 2010 and 2015. The Man-Kendall trend test was used to assess for significant trends over time. RESULTS: We identified 23,015 patients that met study inclusion criteria. Between 2010 and 2015, there was a decline in the use of pelvic RT from 9.8% to 7.5%, although not meeting statistical significance (p = 0.136), and an increase in the use of VBT-C from 4.6% to 7.7% (p = 0.017). Most patients did not receive treatment per either arm of GOG 249, with observation being the most common approach throughout this era, although the percentage of patients observed decreased from 58.1% to 45.8% between 2010 and 2015 (p = 0.003). Further, 21.5% of patients received VBT alone in 2010, increasing to 30.3% by 2015 (p = 0.003). CONCLUSIONS: National practice trends in HIR endometrial cancer reveal that a large number of patients are observed in lieu of receiving adjuvant therapy. Further, the utilization of pelvic RT has declined below utilization of VBT-C, despite a lack of data supporting either improved disease outcomes or toxicity with this experimental regimen on GOG 249.

Immune checkpoint inhibitors and radiosurgery for newly diagnosed melanoma brain metastases.

INTRODUCTION: Brain metastases are common in metastatic melanoma and radiosurgery is often utilized for local control. Immune checkpoint inhibitors (CPIs) play a central role in contemporary melanoma management; however, there is limited data exploring outcomes and potential toxicities for patients treated with CPIs and radiosurgery. METHODS: We retrospectively identified all consecutive cases of newly diagnosed melanoma brain metastases (MBM) treated with Gamma Knife radiosurgery at a single institution between 2012 and 2017, and included only patients that initiated CPIs within 8 weeks before or after radiosurgery. RESULTS: Thirty-eight patients were included with a median follow-up of 31.6 months. Two-year local control was 92%. Median time to out-of-field CNS and extra-CNS progression were 8.4 and 7.9 months, respectively. Median progression-free survival (PFS) was 3.4 months and median overall survival (OS) was not reached (NR). Twenty-five patients (66%) received anti-CTLA4 and 13 patients (34%) received anti-PD-1+/-anti-CTLA4. Compared with anti-CTLA4, patients that received anti-PD-1+/-anti-CTLA4 had significant improvements in time to out-of-field CNS progression (p = 0.049), extra-CNS progression (p = 0.015), and PFS (p = 0.043), with median time to out-of-field CNS progression of NR vs. 3.1 months, median time to extra-CNS progression of NR vs. 4.4 months, and median PFS of 20.3 vs. 2.4 months. Six patients (16%) developed grade ≥ 2 CNS toxicities (grade 2: 3, grade 3: 3, grade 4/5: 0). CONCLUSIONS: Excellent outcomes were observed in patients that initiated CPIs within 8 weeks of undergoing radiosurgery for newly diagnosed MBM. There appears to be an advantage to anti-PD-1 or combination therapy compared to anti-CTLA4.

Rising Rates of Upfront Surgery in Early Locally Advanced Cervical Cancer: What Factors Predict for This Treatment Paradigm?

OBJECTIVE: In this study, we analyzed patterns of care for patients with locally advanced cervical cancer to identify predictors for upfront surgery compared with definitive chemoradiation (CRT). METHODS: The National Cancer Database was queried for patients aged 18 years or older with Federation of Gynecology and Obstetrics IB2-IIB cervical cancer. All patients underwent either upfront hysterectomy with or without postoperative radiation therapy versus definitive CRT. Logistic regression was used to assess variables associated with modality of treatment (surgery vs CRT). RESULTS: Of the 9494 patients included, 2151 (22.7%) underwent upfront surgery. Of those undergoing surgery, 380 (17.7%) had positive margins, 478 (22.2%) had positive nodes, and 458 (21.3%) had pathologic involvement of the parametrium. Under multiple logistic regression, rates of surgery significantly increased from 2004 (12.2%) to 2012 (31.2%) (odds ratio [OR] per year increase, 1.15; confidence interval [CI], 1.12-1.17; P < 0.001). Upfront surgery was more commonly performed in urban (OR, 1.21; 95% CI, 1.03-1.41; P = 0.018) and rural counties (OR, 1.79; 95% CI, 1.24-2.58; P = 0.002), for adenocarcinoma (OR, 2.14; 1.88-2.44; P < 0.001) and adenosquamous (OR, 2.69; 2.11-3.43; P < 0.001) histologies, and in patients from higher median income communities (ORs, 1.19-1.37). Upfront surgery was less common at academic centers (OR, 0.73; 95% CI, 0.58-0.93; P = 0.011). CONCLUSIONS: Rates of upfront surgery relative to definitive CRT have increased significantly over the past decade. In the setting of level 1 evidence supporting the use of definitive CRT alone for these women, the rising rates of upfront surgery raises concern for both unnecessary surgical procedures with higher rates of treatment-related morbidity and greater health care costs.

A comprehensive comparative analysis of treatment modalities for sinonasal malignancies.

BACKGROUND: Sinonasal malignancies are a rare and heterogeneous group of tumors for which there is a paucity of robust data with which to guide management decisions. The authors used the National Cancer Data Base to better understand the presenting characteristics of these tumors and to compare outcomes by treatment modality. METHODS: The National Cancer Data Base was queried for sinonasal malignancies diagnosed between 2004 and 2012. Overall survival was assessed using multivariate analyses and propensity score matching. RESULTS: A total of 11,160 patients were identified for the initial analysis. The majority were male, aged 40 to 69 years, with tumors of the nasal cavity or maxillary sinus. Squamous cell histology was most common. The majority of patients presented with advanced tumor stage but without locoregional lymph node or distant metastases. Treatment modalities were compared for squamous cell carcinomas. In multivariate analysis, compared with surgery alone, patients who received adjuvant radiotherapy (hazard ratio [HR], 0.658 [P<.001]), adjuvant chemoradiotherapy (HR, 0.696 [P = .002]), or neoadjuvant therapy (HR, 0.656 [P = .007]) had improved overall survival. Patients who received radiotherapy alone (HR, 1.294 [P = .001]) or chemotherapy alone (HR, 1.834 [P<.001]) had worse outcomes. These findings were validated in propensity score matching. It is important to note that neoadjuvant chemoradiotherapy was associated with achieving a negative surgical margin (odds ratio, 2.641 [P = .045]). CONCLUSIONS: Surgery is the mainstay of therapy for patients with sinonasal malignancies, but multimodality therapy is associated with improved overall survival. Cancer 2017;123:3040-49. © 2017 American Cancer Society.

Disparities in standard of care treatment and associated survival decrement in patients with locally advanced cervical cancer.

PURPOSE: Standard of care (SOC) treatment for locally advanced cervical cancer includes pelvic external beam radiation (EBRT) with chemotherapy and interdigitated brachytherapy. We evaluated national utilization trends and factors associated with receiving SOC therapy. MATERIALS AND METHODS: We utilized the National Cancer Database (NCDB) to identify women with locally advanced cervical cancer treated with definitive radiation or chemoradiation therapy and stratified these patients by treatment received. RESULTS: We identified 15,194 patients. Only 44.3% of patients received SOC treatment and this group had significantly improved OS. High volume centers, academic centers, comprehensive community cancer centers, private insurance, and higher income, were all associated with an increased likelihood of receiving SOC, whereas Black patients were less likely to receive SOC. We found 26.8% of patients received no radiation boost, 23.8% received an EBRT boost only, and 49.5% of patients received EBRT with brachytherapy. Although an EBRT boost was advantageous over no boost at all (HR 0.720, p<0.001), OS was superior in patients who received brachytherapy (HR 0.554, p<0.001). Patients were more likely to receive no radiotherapy boost if they had lower incomes, Medicaid, were treated at low volume centers, or were treated at non-comprehensive community cancer centers. CONCLUSIONS: SOC for locally advanced cervical cancer offers superior outcomes, yet less than half of patients receive SOC and there are disparities in which patients receive SOC treatment. No additional treatment, including sophisticated EBRT techniques including IMRT or SBRT, can make up for the survival decrement from lack of brachytherapy as a component of definitive care.

Allosteric inhibitors of the Eya2 phosphatase are selective and inhibit Eya2-mediated cell migration.

Eya proteins are essential co-activators of the Six family of transcription factors and contain a unique tyrosine phosphatase domain belonging to the haloacid dehalogenase family of phosphatases. The phosphatase activity of Eya is important for the transcription of a subset of Six1-target genes, and also directs cells to the repair rather than apoptosis pathway upon DNA damage. Furthermore, Eya phosphatase activity has been shown to mediate transformation, invasion, migration, and metastasis of breast cancer cells, making it a potential new drug target for breast cancer. We have previously identified a class of N-arylidenebenzohydrazide compounds that specifically inhibit the Eya2 phosphatase. Herein, we demonstrate that these compounds are reversible inhibitors that selectively inhibit the phosphatase activity of Eya2, but not Eya3. Our mutagenesis results suggest that this class of compounds does not bind to the active site and the binding does not require the coordination with Mg(2+). Moreover, these compounds likely bind within a site on the opposite face of the active site, and function as allosteric inhibitors. We also demonstrate that this class of compounds inhibits Eya2 phosphatase-mediated cell migration, setting the foundation for these molecules to be developed into chemical probes for understanding the specific function of the Eya2 phosphatase and to serve as a prototype for the development of Eya2 phosphatase specific anti-cancer drugs.

Treatment Intensification in Metastatic Hormone-Sensitive Prostate Cancer: An Analysis of Real-World Practice Patterns from the CancerLinQ Database.

BACKGROUND: In metastatic hormone-sensitive prostate cancer (mHSPC), androgen deprivation therapy and standard of care treatment intensification with docetaxel and/or an androgen receptor signaling inhibitor (ARSI) are associated with improved survival outcomes for appropriate patients. METHODS: This retrospective study selected patients with de novo mHSPC diagnosed between 2014 and 2023 from CancerLinQ Discovery®, a United States (US)-based, de-identified clinical database. Patient-level data, including clinical characteristics, treatments, and demographics, were collected from CancerLinQ. Treatment intensification was defined as the use of docetaxel, abiraterone, apalutamide, enzalutamide, or docetaxel plus abiraterone or darolutamide. Patient characteristics and treatment intensification data were analyzed descriptively and using multivariable logistic regression. RESULTS: Of the 3,684 patients with mHSPC, the overall rate of treatment intensification was 58.4% but increased from 32.5% in 2014 to 67.5% in 2023. A relative decline in docetaxel use was accompanied by an increase in ARSI use. Black patients with mHSPC were less likely to receive treatment identification (OR 0.78, 95% CI 0.64-0.95, P = 0.013). Treatment intensification was also less likely for patients of older age and increased ECOG performance status. Despite increasing treatment intensification for Black patients with mHSPC over time, rates of docetaxel use are disproportionately declining relative to White patients. CONCLUSIONS: Treatment intensification rates are increasing to include the majority of patients with mHSPC. However, treatment disparities exist for Black patients, who are less likely to receive intensification. These findings illustrate the importance of promoting treatment intensification in appropriate patients and addressing racial treatment disparities.

Clinical and Dosimetric Impact of 2D kV Motion Monitoring and Intervention in Liver Stereotactic Body Radiation Therapy.

Purpose: Positional errors resulting from motion are a principal challenge across all disease sites in radiation therapy. This is particularly pertinent when treating lesions in the liver with stereotactic body radiation therapy (SBRT). To achieve dose escalation and margin reduction for liver SBRT, kV real-time imaging interventions may serve as a potential solution. In this study, we report results of a retrospective cohort of liver patients treated using real-time 2D kV-image guidance SBRT with emphasis on the impact of (1) clinical workflow, (2) treatment accuracy, and (3) tumor dose. Methods and Materials: Data from 33 patients treated with 41 courses of liver SBRT were analyzed. During treatment, planar kV images orthogonal to the treatment beam were acquired to determine treatment interventions, namely treatment pauses (ie, adequacy of gating thresholds) or treatment shifts. Patients were shifted if internal markers were >3 mm, corresponding to the PTV margin used, from the expected reference condition. The frequency, duration, and nature of treatment interventions (ie, pause vs shift) were recorded, and the dosimetric impact associated with treatment shifts was estimated using a machine learning dosimetric model. Results: Of all fractions delivered, 39% required intervention, which took on average 1.9 ± 1.6 minutes and occurred more frequently in treatments lasting longer than 7 minutes. The median realignment shift was 5.7 mm in size, and the effect of these shifts on minimum tumor dose in simulated clinical scenarios ranged from 0% to 50% of prescription dose per fraction. Conclusion: Real-time kV-based imaging interventions for liver SBRT minimally affect clinical workflow and dosimetrically benefit patients. This potential solution for addressing positional errors from motion addresses concerns about target accuracy and may enable safe dose escalation and margin reduction in the context of liver SBRT.

Pilot Curriculum for Continued Professional Development of Radiation Oncology Nurses.

Purpose: Limited structured educational programs are available for the continued professional development of radiation oncology nurses. In this study, we evaluated a pilot curriculum focusing on clinical workflow and toxicity management for radiation oncology nurses at a single university-affiliated medical center network. Methods and Materials: Based on a previous multi-institutional needs assessment, a targeted curriculum on clinical workflow and toxicity management was developed, including didactic lectures, written disease-specific toxicity management guidelines, and standardized medication/laboratory order preference lists in the electronic health record. An anonymized survey was circulated to all participants pre- and postcurriculum. The survey was composed of Likert-type subjective questions and 11 objective knowledge-based questions (KBQs). Paired Likert-type data were analyzed using Wilcoxon signed ranks test. Objective question data were compared with the McNamar's mid P test. Results: Thirteen nurses participated in the pilot curriculum and 100% completed pre- and post curriculum surveys. After the didactics, nurses reported a significant increase in their understanding of the responsibilities of a nurse and overall process of care and their ability to explain computed tomography simulation, as well as their ability to assess, manage, and grade radiation-related toxicities (P < .01). There was significant improvement in the percent of correct answers on objective KBQs from a baseline of 52% to 80% after the curriculum (P < .01). Qualitatively, 70% (9/13) of nurses rated the curriculum as "extremely useful" and 30% (4/13) as "quite useful." Conclusions: Our pilot curriculum using a combination of in-person formal didactics, toxicity management guidelines, and electronic health record based order preference lists was well-received and showed promising results on KBQ assessment. This work may be used to guide the development of larger curricula for nurse onboarding and continuing education in a multicenter setting.

Cardiovascular Mortality and Duration of Androgen Deprivation in Locally Advanced Prostate Cancer: Long-term Update of NRG/RTOG 9202.

BACKGROUND: Androgen deprivation therapy (ADT) has been associated with coronary heart disease and myocardial infarction (MI) in prostate cancer patients, but controversy persists regarding its effects on cardiovascular mortality (CVM). OBJECTIVE: We assessed the long-term relationship between ADT and CVM in a prostate cancer randomized trial (NRG Oncology/Radiation Therapy Oncology Group 9202). DESIGN, SETTING, AND PARTICIPANTS: From 1992 to 1995, 1554 men with locally advanced prostate cancer (T2c-T4, prostate-specific antigen <150 ng/ml) received radiotherapy with 4 mo (short-term [STADT]) versus 28 mo (longer-term [LTADT]) of ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using the Fine-Gray and Cox regression models, the relationship between ADT and mortality was evaluated. RESULTS AND LIMITATIONS: With a median follow-up of 19.6 yr, LTADT was associated with improved overall survival (OS) versus STADT (adjusted hazard ratio [HR] 0.88; p = 0.03) and prostate cancer survival (subdistribution HR [sHR] 0.70, p = 0.003). Comparing LTADT with STADT, prostate cancer mortality improved by 6.0% (15.6% [95% confidence interval 13.0-18.3%] vs 21.6% [18.6-24.7%]) at 15 yr, while CVM increased by 2.2% (14.9% [12.4-17.6%] vs 12.7% [10.4-15.3%]). In multivariable analyses, LTADT was not associated with increased CVM versus STADT (sHR 1.22 [0.93-1.59]; p = 0.15). An association between LTADT and MI death was detected (sHR 1.58 [1.00-2.50]; p = 0.05), particularly in patients with prevalent cardiovascular disease (CVD; sHR 2.54 [1.16-5.58]; p = 0.02). CONCLUSIONS: With 19.6 yr of follow-up, LTADT was not significantly associated with increased CVM in men with locally advanced prostate cancer. Patients may have increased MI mortality with LTADT, particularly those with baseline CVD. Overall, there remained a prostate cancer mortality benefit and no OS detriment with LTADT. PATIENT SUMMARY: In a long-term analysis of a large randomized prostate cancer trial, radiation with 28 mo of hormone therapy did not increase the risk of cardiovascular death significantly versus 4 mo of hormone therapy. Future studies are needed for patients with pre-existing heart disease, who may have an increased risk of myocardial infarction death with longer hormone use.

Fiducial Markers Allow Accurate and Reproducible Delivery of Liver Stereotactic Body Radiation Therapy.

Fiducial markers are utilized for image guided radiotherapy (IGRT) alignment during the delivery of liver stereotactic body radiosurgery (SBRT). There are limited data demonstrating the impact of matching fiducials on the accuracy of liver SBRT. This study quantifies the benefit of fiducial-based alignment and improvements in inter-observer reliability. Nineteen patients with 24 liver lesions were treated with SBRT. Target localization was performed using fiducial markers on cone-beam computed tomography (CBCT). Each CBCT procedure was retrospectively realigned to match both the liver edge and fiducial markers. The shifts were recorded by seven independent observers. Inter-observer variability was analyzed by calculating the mean error and uncertainty for the set-up. The mean absolute Cartesian error observed from fiducial and liver edge-based alignment was 1.5 mm and 5.3 mm, respectively. The mean uncertainty from fiducial and liver edge-based alignment was 1.8 mm and 4.5 mm, respectively. An error of 5 mm or greater was observed 50% of the time when aligning to the liver surface versus 5% of the time when aligning to fiducial markers. Aligning to the liver edge significantly increased the error, resulting in increased shifts when compared to alignment to fiducials. Tumors of 3 cm or farther from the liver dome had higher mean errors when aligned without fiducials (4.8 cm vs. 4.4 cm, p = 0.003). Our data support the use of fiducial markers for safer and more accurate liver SBRT.

Multicenter analysis of stereotactic radiosurgery for multiple brain metastases from EGFR and ALK driven non-small cell lung cancer.

INTRODUCTION: Patients with brain metastases (BrMs) arising from EGFR and ALK driven non-small cell lung cancer (NSCLC) have favorable prognoses and evolving treatment options. We evaluated multicenter outcomes for stereotactic radiosurgery (SRS) to multiple (≥4) BrMs, where randomized data remain limited. METHODS: Data were collected retrospectively from 5 academic centers on EGFR and ALK NSCLC who received SRS to ≥4 BrMs with their first SRS treatment between 2008 and 2018. Analyzed endpoints included overall survival (OS), freedom from CNS progression (FFCNSP), and freedom from whole-brain radiotherapy (FFWBRT). RESULTS: Eighty-nine patients (50 EGFR, 39 ALK) received a total of 159 SRS treatments to 1,080 BrMs, with a median follow up of 51.3 months. The median number of BrMs treated with SRS treatment-1 was 6 (range 4-26) and median for all treatments was 9 (range 4-47). Sixteen patients (18 %) had received WBRT prior to SRS treatment-1. The median OS was 24.2, 21.2, and 33.2 months for all patients, EGFR, and ALK subsets, respectively. After multivariable adjustment, only receipt of a next-generation tyrosine kinase inhibitor was associated with OS (HR 0.40, p = 0.005). No differences in OS were observed based on number of BrMs treated. The median FFCNSP was 9.4, 11.6, and 7.5 months, for all patients, EGFR, and ALK subsets, respectively. After multivariable adjustment, the number of BrMs (continuous) treated during treatment-1 was the only negative prognostic factor associated with FFCNSP (HR 1.071, p = 0.045). The 5-year FFWBRT was 73.6 %. CONCLUSIONS: This multicenter analysis over a >10-year period demonstrated favorable OS, FFCNSP, and FFWBRT, in patients with EGFR and ALK driven NSCLC receiving SRS to ≥4 BrMs. These data support SRS as an option in the upfront and salvage setting for higher burden CNS disease in this population.

The American Brachytherapy Society and Indian Brachytherapy Society consensus statement for the establishment of high-dose-rate brachytherapy programs for gynecological malignancies in low- and middle-income countries.

PURPOSE: The global cervical cancer burden is disproportionately high in low- and middle-income countries (LMICs), and outcomes can be governed by the accessibility of appropriate screening and treatment. High-dose-rate (HDR) brachytherapy plays a central role in cervical cancer treatment, improving local control and overall survival. The American Brachytherapy Society (ABS) and Indian Brachytherapy Society (IBS) collaborated to provide this succinct consensus statement guiding the establishment of brachytherapy programs for gynecological malignancies in resource-limited settings. METHODS AND MATERIALS: ABS and IBS members with expertise in brachytherapy formulated this consensus statement based on their collective clinical experience in LMICs with varying levels of resources. RESULTS: The ABS and IBS strongly encourage the establishment of HDR brachytherapy programs for the treatment of gynecological malignancies. With the consideration of resource variability in LMICs, we present 15 minimum component requirements for the establishment of such programs. Guidance on these components, including discussion of what is considered to be essential and what is considered to be optimal, is provided. CONCLUSIONS: This ABS/IBS consensus statement can guide the successful and safe establishment of HDR brachytherapy programs for gynecological malignancies in LMICs with varying levels of resources.

Comparison of first-line radiosurgery for small-cell and non-small cell lung cancer brain metastases (CROSS-FIRE).

INTRODUCTION: Historical reservations regarding stereotactic radiosurgery (SRS) for small-cell lung cancer (SCLC) brain metastases include concerns for short-interval and diffuse central nervous system (CNS) progression, poor prognoses, and increased neurological mortality specific to SCLC histology. We compared SRS outcomes for SCLC and non-small cell lung cancer (NSCLC) where SRS is well established. METHODS: Multicenter first-line SRS outcomes for SCLC and NSCLC from 2000 to 2022 were retrospectively collected (n = 892 SCLC, n = 4785 NSCLC). Data from the prospective Japanese Leksell Gamma Knife Society (JLGK0901) clinical trial of first-line SRS were analyzed as a comparison cohort (n = 98 SCLC, n = 814 NSCLC). Overall survival (OS) and CNS progression were analyzed using Cox proportional hazard and Fine-Gray models, respectively, with multivariable adjustment for cofactors including age, sex, performance status, year, extracranial disease status, and brain metastasis number and volume. Mutation-stratified analyses were performed in propensity score-matched retrospective cohorts of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) positive NSCLC, mutation-negative NSCLC, and SCLC. RESULTS: OS was superior for patients with NSCLC compared to SCLC in the retrospective dataset (median OS = 10.5 vs 8.6 months; P < .001) and in the JLGK0901 dataset. Hazard estimates for first CNS progression favoring NSCLC were similar in both datasets but reached statistical significance in the retrospective dataset only (multivariable hazard ratio = 0.82, 95% confidence interval = 0.73 to 0.92, P = .001). In the propensity score-matched cohorts, there were continued OS advantages for NSCLC patients (median OS = 23.7 [EGFR and ALK positive NSCLC] vs 13.6 [mutation-negative NSCLC] vs 10.4 months [SCLC], pairwise P values < 0.001), but no statistically significant differences in CNS progression were observed in the matched cohorts. Neurological mortality and number of lesions at CNS progression were similar for NSCLC and SCLC patients. Leptomeningeal progression was increased in patients with NSCLC compared to SCLC in the retrospective dataset only (multivariable hazard ratio = 1.61, 95% confidence interval = 1.14 to 2.26, P = .007). CONCLUSIONS: After SRS, SCLC histology was associated with shorter OS compared to NSCLC. CNS progression occurred earlier in SCLC patients overall but was similar in patients matched on baseline factors. SCLC was not associated with increased neurological mortality, number of lesions at CNS progression, or leptomeningeal progression compared to NSCLC. These findings may better inform clinical expectations and individualized decision making regarding SRS for SCLC patients.

Practical Implementation of Emergent After-Hours Radiation Treatment Process Using Remote Treatment Planning on Optimized Diagnostic CT Scans.

The purpose of this report is to present the implementation of a process for after-hours radiation treatment (RT) utilizing remote treatment planning based on optimized diagnostic computed tomography (CT) scans for the urgent palliative treatment of inpatients. A standardized operating procedure was developed by an interprofessional panel to improve the quality of after-hours RT and minimize the risk of treatment errors. A new diagnostic CT protocol was created that could be performed after-hours on hospital scanners and would ensure a reproducible patient position and adequate field of view. An on-call structure for dosimetry staff was created utilizing remote treatment planning. The optimized CT protocol was developed in collaboration with the radiology department, and a novel order set was created in the electronic health system. The clinical workflow begins with the radiation oncologist notifying the on-call team (therapist, dosimetrist, and physicist) and obtaining an optimized diagnostic CT scan on a hospital-based scanner. The dosimetrist remotely creates a plan; the physicist checks the plan; and the patient is treated. Plans are intentionally simple (parallel opposed fields, symmetric jaws) to expedite care and reduce the risk of error. Education on the new process was provided for all relevant staff. Our process was successfully implemented with the use of an optimized CT protocol and remote treatment planning. This approach has the potential to improve the quality and safety of emergent after-hours RT by better approximating the normal process of care.

Breast cancer epithelial-to-mesenchymal transition: examining the functional consequences of plasticity.

The epithelial-to-mesenchymal transition (EMT) is a critical developmental process that has recently come to the forefront of cancer biology. In breast carcinomas, acquisition of a mesenchymal-like phenotype that is reminiscent of an EMT, termed oncogenic EMT, is associated with pro-metastatic properties, including increased motility, invasion, anoikis resistance, immunosuppression and cancer stem cell characteristics. This oncogenic EMT is a consequence of cellular plasticity, which allows for interconversion between epithelial and mesenchymal-like states, and is thought to enable tumor cells not only to escape from the primary tumor, but also to colonize a secondary site. Indeed, the plasticity of cancer cells may explain the range of pro-metastatic traits conferred by oncogenic EMT, such as the recently described link between EMT and cancer stem cells and/or therapeutic resistance. Continued research into this relationship will be critical in developing drugs that block mechanisms of breast cancer progression, ultimately improving patient outcomes.

Narrative review of immune checkpoint inhibitors and radiation therapy for brain metastases.

Radiation therapy plays a key role in the management of intracranial metastatic disease. Historically, systemic therapy was able to address extracranial disease but not cross the blood-brain barrier and radiation therapy and surgery were the only mechanisms to treat intracranial metastases. There are now several examples of contemporary systemic therapies with central nervous system efficacy in some patients. With such improvements in systemic therapies, patients are living longer and the optimal management of brain metastases is becoming an increasingly important clinical priority. However, the role of radiation therapy remains critical in treating brain metastases. The concurrent use of new systemic therapies with radiation brings about novel and significant questions regarding potential synergy between these therapies in the brain in regard to both oncologic efficacy and toxicity. One important systemic therapy to consider is immune checkpoint inhibitors. These drugs are now at the forefront of management of many malignancies and have changed the landscape of treatment for many common cancers, particularly those with a predilection for brain metastases. In this review we will examine the existing data on the efficacy and toxicity of concurrent radiation therapy and immunotherapy for brain metastases and explore potential mechanisms underlying the published clinical observations.