A PI3K gene expression signature predicts for recurrence in early-stage non-small cell lung cancer treated with stereotactic body radiation therapy.

INTRODUCTION: Increasingly, early-stage non-small cell lung cancer (NSCLC) is treated with stereotactic body radiation therapy (SBRT). Although treatment is generally effective, a small subset of tumors will recur because of radioresistance. Preclinical studies suggested PI3K-AKT-mTOR activation mediates radioresistance. This study sought to validate this finding in tumor samples from patients who underwent SBRT for NSCLC. METHODS: Patients with T1-3N0 NSCLC treated with SBRT at our institution were included. Total RNA of formalin-fixed paraffin-embedded tumor biopsy specimens (pretherapy) was isolated and analyzed using the Clariom D assay. Risk scores from a PI3K activity signature and four published NSCLC signatures were generated and dichotomized by the median. Kaplan-Meier curves and Cox regressions were used to analyze their association with recurrence and overall survival (OS). The PI3K signature was also tested in a data set of resected NSCLC for additional validation. RESULTS: A total of 92 patients were included, with a median follow-up of 18.3 months for living patients. There was no association of any of the four published gene expression signatures with recurrence or OS. However, high PI3K risk score was associated with higher local recurrence (hazard ratio [HR], 11.72; 95% CI, 1.40-98.0; p = .023) and worse disease-free survival (DFS) (HR, 3.98; 95% CI, 1.57-10.09; p = .0035), but not OS (p = .49), regional recurrence (p = .15), or distant recurrence (p = .85). In the resected NSCLC data set (n = 361), high PI3K risk score was associated with decreased OS (log-rank p = .013) but not DFS (p = 0.54). CONCLUSIONS: This study validates that higher PI3K activity, measured by gene expression, is associated with local recurrence and worse DFS in early-stage NSCLC patients treated with SBRT. This may be useful in prognostication and/or tailoring treatment, and merits further validation.

The Association of Improved Overall Survival with NSAIDs in Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICI) are commonly used in the management of patients with advanced non-small cell lung cancer (NSCLC), but response is suboptimal. Preclinical data suggest ICI efficacy may be enhanced with concomitant nonsteroidal anti-inflammatory (NSAID) medications. PATIENTS AND METHODS: In this retrospective study, the Veterans Health Administration Corporate Data Warehouse was queried for patients diagnosed with NSCLC and treated with ICI from 2010 to 2018. Concomitant NSAID use was defined as NSAID dispensation by a VA pharmacy within 90 days of the any ICI infusion. To mitigate immortal time bias, patients who started NSAIDs 60 or more days after ICI initiation were excluded from analysis. Survival was measured from start of ICI. RESULTS: We identified 3634 patients with NSCLC receiving ICI; 2336 (64.3%) were exposed to concomitant NSAIDs. On multivariable analysis, NSAIDs were associated with better overall survival (HR = 0.90; 95% CI, 0.83-0.98; P = .010). When stratifying by NSAID type, diclofenac was the only NSAID with significant association with overall survival (HR = 0.75; 95% CI, 0.68-0.83; P < .001). Propensity score matching of the original cohort yielded 1251 patients per cohort balanced in characteristics. NSAIDs remained associated with improved overall survival (HR = 0.85; 95% CI, 0.78-0.92; P < .001). CONCLUSION: This study of Veterans with NSCLC treated with ICI demonstrated that concomitant NSAIDs are associated with longer OS. This may indicate that NSAIDs can enhance ICI-induced antitumor immunity and should prospectively validated.

Impact of concomitant fibrates on immunotherapy outcomes for advanced non-small cell lung cancer.

BACKGROUND: Peroxisome proliferator-activated receptor agonists such as fibrates restore oxidative metabolism in cytotoxic T-lymphocytes, thereby enhancing response to immune checkpoint inhibitors (ICI) in preclinical models. However, there is no evidence in humans on the clinical impact of fibrates as an adjunct to ICI. METHODS: In this cohort study of Veterans with non-small cell lung cancer (NSCLC) receiving ICI, fibrate exposure was defined as a prescription filled within 90 days of an ICI infusion. Overall survival (OS), measured from the start of ICI, was compared between exposed and unexposed Veterans. Cox multivariable analysis (MVA) was used to identify factors associated with OS. A sensitivity analysis of Veterans with stage IV NSCLC who received docetaxel without ICI was similarly performed. RESULTS: The ICI cohort included 3593 Veterans, of whom 301 (8.5%) coincidentally received a fibrate. Veterans receiving fibrates were more likely to be older, white, male, and married, and to have greater comorbidity burden, but less likely to receive chemotherapy. Coincidental fibrates were associated with improved OS both on MVA (HR 0.86, 95%CI 0.75-0.99) and in a matched subset (HR 0.75, 95%CI 0.63-0.90). In contrast, among the cohort of 968 Veterans treated with chemotherapy, fibrates did not have a significant impact on OS by MVA (HR 0.99, 95%CI 0.79-1.25) or in a matched subset (HR 1.02, 95%CI CI 0.75-1.39). CONCLUSIONS: Concomitant fibrates are associated with improved OS among NSCLC patients receiving ICI but not among those receiving chemotherapy. This hypothesis-generating observation supports a potential role for fibrates as an adjunct to immunotherapy.

The Association of Radiation Therapy and Chemotherapy on Overall Survival in Merkel Cell Carcinoma: A Population-Based Analysis.

Purpose/objective(s) Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neoplasm traditionally managed with surgical resection followed by radiotherapy (RT). With the recent approval of checkpoint inhibitors, chemotherapy is less commonly utilized. We analyzed the impact of RT and chemotherapy on overall survival (OS) in patients with MCC using Surveillance, Epidemiology, and End Results (SEER), a population-level database. Materials and methods We performed retrospective analyses on SEER 18 Custom Data registries for MCC (ICD-0-3 8247). Data from 1980 to 2016 was queried for analysis, and an initial list of 9,792 patients was populated (ICD: C00, C07.9, C44, C80.9). Selection for cases with chemotherapy and RT status, single primary tumor, primary tumor location and surgery treatment type yielded 5,002 cases for analysis. Baseline characteristics were compared with Chi-square or Mann-Whitney U test. Univariate and multivariable analysis using Kaplan-Meier and Cox proportional hazards regression modeling were performed. Propensity-score matched analysis with inverse probability of treatment weighting (IPTW) was used to account for indication bias. Results Median follow-up time was 178 months (68 to 217 months). Independent prognostic factors positively correlated with increased OS, for both unadjusted Multivariate analysis and IPTW adjusted MVA were age, male sex, year of diagnosis, stage, RT status, and chemotherapy status. On adjusted MVA, use of chemotherapy was associated with worse OS (hazard ratio: 1.22 [95% CI 1.1-1.35], p<0.001), whereas RT was associated with improved OS (HR:0.9 [95% CI, 0.83-0.97], p=0.008). Conclusions The current study demonstrates that RT is associated with improved survival for patients with MCC. Chemotherapy was associated with worse OS. This supports the recent clinical shift towards immune checkpoints inhibitors as standard of care in the metastatic setting, and promising trials in the adjuvant and advanced settings.

Development of a MicroRNA Signature Predictive of Recurrence and Survival in Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Optimal patient selection for radiotherapy in pancreatic ductal adenocarcinoma (PDAC) is unestablished. Molecular profiling may select patients at high risk for locoregional recurrence (LRR) who would benefit from radiation. METHODS: We included resectable pancreatic cancer (R-PDAC) patients, divided into training and validation cohorts, treated among three institutions with surgery and adjuvant chemotherapy, and borderline resectable or locally advanced pancreatic cancer (BR/LA-PDAC) patients treated with chemotherapy with or without radiation at the primary study institution. We isolated RNA from R-PDAC surgical specimens. Using NanoString, we identified miRNAs differentially expressed between normal and malignant pancreatic tissue. ElasticNet regression identified two miRNAs most predictive of LRR in the training cohort, miR-181b/d and miR-575, which were used to generate a risk score (RS). We evaluated the association of the median-dichotomized RS with recurrence and overall survival (OS). RESULTS: We identified 183 R-PDAC and 77 BR/LA-PDAC patients with median follow up of 37 months treated between 2001 and 2014. On multivariable analysis of the R-PDAC training cohort (n = 90), RS was associated with worse LRR (HR = 1.34; 95%CI 1.27-11.38; p = 0.017) and OS (HR = 2.89; 95%CI 1.10-4.76; p = 0.027). In the R-PDAC validation cohort, RS was associated with worse LRR (HR = 2.39; 95%CI 1.03-5.54; p = 0.042), but not OS (p = 0.087). For BR/LA-PDAC, RS was associated with worse LRR (HR = 2.71; 95%CI 1.14-6.48; p = 0.025), DR (HR = 1.93; 95%CI 1.10-3.38; p = 0.022), and OS (HR = 1.97; 95%CI 1.17-3.34; p = 0.011). Additionally, after stratifying by RS and receipt of radiation in BR/LA-PDAC patients, high RS patients who did not receive radiation had worse LRR (p = 0.018), DR (p = 0.006), and OS (p < 0.001) compared to patients with either low RS or patients who received radiation, irrespective of RS. CONCLUSIONS: RS predicted worse LRR and OS in R-PDAC and worse LRR, DR, and OS in BR/LA-PDAC. This may select patients who would benefit from radiation and should be validated prospectively.

Malignant ossifying fibromyxoid tumor of the brain treated with post-operative fractionated stereotactic radiation therapy: A case report and literature review.

BACKGROUND: Ossifying fibromyxoid tumor (OFMT) is a rare musculoskeletal soft-tissue neoplasm of uncertain histogenesis most frequently occurring in the lower extremities. Conventionally, considered benign, these tumors are often managed by surgical resection followed by surveillance. However, malignant OFMTs with an increased propensity for local recurrence and distant metastasis have been recently identified, and the role of adjuvant therapy in these more aggressive cases is unclear. CASE DESCRIPTION: We present, to the best of our knowledge, the first reported case of a primary, malignant, and intracranial OFMT. A 29-year-old female presented with recurrent headaches secondary to a large mass in her right frontal lobe. She underwent gross total resection of the brain mass with final pathology consistent with malignant OFMT demonstrating high-risk features including increased cellularity, grade, and mitotic activity. Due to these high-risk features, she received postoperative fractionated stereotactic radiation therapy (FSRT) to the resection cavity, and to the best of our knowledge, she represents the only known patient with OFMT to be treated with adjuvant FSRT. She tolerated the adjuvant treatment well with no acute or late toxicities and remains disease-free over 5 ½ years after resection. CONCLUSION: Adjuvant FSRT appears to be a safe and efficacious approach for managing this rare intracranial disease presentation. We review this patient's clinical course in the context of the literature to demonstrate the difficulties associated with accurate diagnosis of this rare tumor and the controversial role of adjuvant therapy in preventing disease recurrence in this patient population.

Association of Pre- and Posttreatment Neutrophil-Lymphocyte Ratio With Recurrence and Mortality in Locally Advanced Non-Small Cell Lung Cancer.

OBJECTIVES: Neutrophil-lymphocyte ratio (NLR) has been associated with mortality in non-small cell lung cancer (NSCLC), but its association with recurrence in locally advanced NSCLC (LA-NSCLC), specifically, is less established. We hypothesized pre- and posttreatment NLR would be associated with recurrence and mortality. METHODS: We studied the association of pretreatment NLR (pre-NLR) and posttreatment NLR at 1 (post-NLR1) and 3 months (post-NLR3) with outcomes in patients with LA-NSCLC treated with chemoradiation. Pre-NLR was dichotomized by 5, an a priori cutoff previously shown to be prognostic in LA-NSCLC. Post-NLR1 and post-NLR3 were dichotomized by their medians. RESULTS: We identified 135 patients treated with chemoradiation for LA-NSCLC between 2007 and 2016. Median follow-up for living patients was 61.1 months. On multivariable analysis, pre-NLR ≥ 5 was associated with worse overall survival (HR = 1.82; 95% CI 1.15 - 2.88; p = 0.011), but not with any recurrence, locoregional recurrence, or distant recurrence. Post-NLR1 ≥ 6.3 was not associated with recurrence or survival. Post-NLR3 ≥ 6.6 was associated with worse overall survival (HR = 3.27; 95% CI 2.01- 5.31; p < 0.001), any recurrence (HR = 2.50; 95% CI 1.53 - 4.08; p < 0.001), locoregional recurrence (HR = 2.50; 95% CI 1.40 - 4.46; p = 0.002), and distant recurrence (HR = 2.53; 95% CI 1.49 - 4.30; p < 0.001). CONCLUSION: Pretreatment NLR is associated with worse overall survival and posttreatment NLR is associated with worse survival and recurrence. These findings should be validated independently and prospectively studied.

A Pilot Trial Evaluating Stereotactic Body Radiation Therapy to Induce Hyperemia in Combination With Transarterial Chemoembolization for Hepatocellular Carcinoma.

PURPOSE: Despite the survival benefit of transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC), a majority of tumors recur, attributed to hypovascularity and treatment resistance. Preclinical studies show that moderate radiation doses induce changes in tumor permeability and perfusion, suggesting an opportunity for TACE sensitization by radiation. In this prospective phase 1 trial, we evaluated the feasibility, safety, tolerability, response, and functional magnetic resonance imaging (MRI) changes associated with single-fraction stereotactic body radiation therapy (SBRT) followed by TACE within 24 hours. METHODS AND MATERIALS: Patients with HCC, 1 to 3 lesions, Childs-Pugh A/B liver function, and no major vascular invasion were enrolled. The primary objective was to establish the feasibility of single-dose SBRT (7.5 or 10 Gy) followed by TACE within 24 hours. Secondary endpoints included safety, tolerability, perfusional changes via functional MRI, overall response rate (ORR), clinical benefit rate (CBR), freedom from local progression, progression-free survival, and overall survival. RESULTS: Sixteen patients were enrolled, and 13 received SBRT and TACE. Median follow-up was 15.3 months. Best overall ORR and CBR were 76.9% and 92.3%, respectively. The 1- and 3-month ORR was 76.9% and 69.2%, respectively, and 1- and 3-month CBR was 92.3% and 69.2%, respectively. Median overall survival, progression-free survival, and freedom from local progression were 14.0, 5.2, and 5.9 months, respectively. Crude rates of grade 1+ and grade 2+ toxicity were 85% and 38%, respectively. No grade 3 to 4 toxicities were recorded. One grade 5 toxicity occurred due to hemorrhage 4 days after TACE. On dynamic contrast-enhanced MRI, the transfer rate constant from blood plasma to extracellular extravascular space (kpe) increased within 6 hours post-SBRT but decreased by 24 hours. CONCLUSIONS: We hypothesized a strategy of SBRT preceding TACE for the purpose of enhancing TACE delivery and efficacy and tested this strategy in a small pilot study. We found that single-dose SBRT followed by TACE within 24 hours is feasible and tolerable. Dynamic contrast-enhanced MRI revealed acute changes in tumor permeability/perfusion after SBRT. Additional studies are needed to establish the safety and efficacy of this combination and the effects of SBRT on the HCC microenvironment.

Recurrence After Stereotactic Body Radiation Therapy Versus Lobectomy for Non-Small Cell Lung Cancer.

BACKGROUND: Although lobectomy remains the standard of care for early-stage non-small cell lung cancer, several studies suggest equipoise between lobectomy and stereotactic body radiation therapy (SBRT). However randomized evidence is lacking. We compared outcomes of early-stage non-small cell lung cancer patients treated with lobectomy or SBRT. METHODS: We included clinical T1-2N0 non-small cell lung cancer treated with lobectomy or SBRT to a biologically effective dose of ≥100 Gy10. We used Cox proportional hazards and nearest-neighbor propensity score (2:1) matching to adjust for confounders. Kaplan-Meier curves were used to assess survival and recurrence. RESULTS: We identified 554 patients treated with lobectomy (n = 389) or SBRT (n = 165) at our institution between 2008 and 2018. After propensity score matching, there were 132 SBRT patients and 85 lobectomy patients. SBRT was associated with increased local recurrence (hazard ratio [HR], 6.80; 95% confidence interval [CI], 1.92-24.10; P = .003) and regional nodal recurrence (HR, 2.58; 95% CI, 1.17-5.68; P = .018), and with worse overall survival (HR, 2.00; 95% CI, 1.21-3.32; P = .007) and progression-free survival (HR, 2.34; 95% CI, 1.50-3.67; P < .001). There was no difference in distant recurrence (HR, 1.19; 95% CI, 0.57-2.52; P = .64). CONCLUSIONS: We found superior outcomes in patients with early-stage non-small cell lung cancer treated with lobectomy compared with SBRT, including locoregional control. These findings should be interpreted with caution because of selection bias but underscore the importance of robust randomized prospective data to clarify the relative efficacy of these modalities.

Linear accelerator-based radiosurgery is associated with lower incidence of radionecrosis compared with gamma knife for treatment of multiple brain metastases.

BACKGROUND: Gamma knife (GK) and linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) both offer excellent local control in the management of multiple brain metastases. The efficacy and toxicity of LINAC and GK SRS have not been directly compared in the modern era. We studied outcomes in patients treated with LINAC SRS and GK at two separate institutions. METHODS: We identified patients treated with either LINAC or GK who were treated to ≥2 lesions and had available follow up. LINAC patients were treated using single-isocenter multitarget technique. We used Cox regression, Fine and Gray competing risks regression, and nearest neighbor propensity score matching to account for confounders and imbalance between cohorts. Kaplan-Meier curves were used to estimate overall survival and rates of radionecrosis. RESULTS: We identified 391 patients who were treated in 537 courses to a total 2699 lesions (LINAC: 1014, GK: 1685). After propensity score matching, GK was associated with similar overall survival (HR = 0.86; 95% CI 0.59-1.24; p = 0.41) and higher rate of radionecrosis (HR = 3.83; 95% CI 1.66-8.84; p = 0.002) compared to LINAC. In a secondary propensity score matched analysis comparing radionecrosis in single-fraction LINAC and GK, GK remained associated with higher incidence of radionecrosis (HR = 4.42; 95% CI 1.28-15.29; p = 0.019). CONCLUSIONS: In this multi-institutional study, we found similar overall survival with lower incidence of radionecrosis in patients treated with LINAC compared to GK SRS. These findings are hypothesis generating and should be validated in an independent cohort.

Single-Isocenter Multitarget Stereotactic Radiosurgery Is Safe and Effective in the Treatment of Multiple Brain Metastases.

PURPOSE: Multiple studies have reported favorable outcomes for stereotactic radiosurgery (SRS) in the treatment of limited brain metastases. An obstacle of SRS in the management of numerous metastases is the longer treatment time using traditional radiosurgery. Single-isocenter multitarget (SIMT) SRS is a novel technique that permits rapid therapy delivery to multiple metastases. There is a lack of clinical evidence regarding its efficacy and safety. We report the outcomes of patients treated with this technique. METHODS AND MATERIALS: We reviewed the records of patients with intact or resected brain metastases treated with SRS in 1 to 5 fractions using SIMT technique at our institution, with at least 1 available follow-up brain magnetic resonance imaging. Survival, disease control, and toxicity were evaluated using Cox regression, logistic regression, and Kaplan-Meier analysis. RESULTS: We identified 173 patients with 1014 brain metastases. Median follow up was 12.7 months. Median beam-on time was 4.1 minutes. The median dose to the brain was 219.4 cGy. Median overall survival and freedom from intracranial progression were 13.2 and 6.3 months, respectively. Overall survival did not differ between patients treated with greater than or less than 4 lesions (hazard ratio, 1.03; 95% confidence interval 0.66-1.61; P = .91). Actuarial 1- and 2-year local control were 99.0% and 95.1%, respectively. Rates of grade 2 and grade 3 or higher radionecrosis were 1.4% and 0.9%, respectively. CONCLUSIONS: SIMT radiosurgery delivered in 1 to 5 fractions offers excellent local control and acceptable toxicity in the treatment of multiple intact and postoperative brain metastases. This technique should be evaluated prospectively.

Stereotactic body radiation therapy is associated with improved overall survival compared to chemoradiation or radioembolization in the treatment of unresectable intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly lethal malignancy. For patients with locally advanced, unresectable disease, numerous liver-directed therapy options exist, including chemoradiation (CRT), stereotactic body radiation therapy (SBRT), and transarterial radioembolization (TARE). There is no randomized data to inform clinicians regarding the optimal treatment modality. METHOD: We used the National Cancer Database (NCDB) to study the overall survival (OS) of patients with ICC treated with CRT, SBRT, and TARE. We used Cox proportional hazards modeling and inverse probability of treatment weighting (IPTW) to account for confounding variables. RESULTS: We identified 170 patients with unresected ICC treated with SBRT (n = 37), CRT (n = 61), or TARE (n = 72). SBRT was associated with higher OS compared to CRT (hazard ratio [HR] = 0.37; 95% confidence interval [CI] 0.20-0.68; p = 0.001) and TARE (HR = 0.40; 95% CI 0.22-0.74; p = 0.003). On multivariable analysis, SBRT remained associated with higher OS compared to CRT (HR = 0.44; 95% CI 0.21-0.91; p = 0.028) and TARE (HR = 0.42; 95% CI 0.21-0.84; p = 0.014). After IPTW (Bonferroni-adjusted significance threshold, α = 0.017), SBRT again had a statistically significant association with higher OS compared to CRT (HR = 0.22; 95% CI 0.11-0.44; p < 0.0001) and was nominally associated TARE (HR = 0.58; 95% CI 0.37-0.91; p = 0.019). CONCLUSIONS: We found SBRT is associated with higher OS when compared to CRT or TARE for the treatment of unresectable ICC. Due to the retrospective nature of the study and potential selection bias, these findings should be evaluated prospectively.

Association of Liver-Directed Local Therapy With Overall Survival in Adults With Metastatic Intrahepatic Cholangiocarcinoma.

Importance: Intrahepatic cholangiocarcinoma is an aggressive hepatobiliary malignant neoplasm characterized by local progression and frequent metastasis. Definitive local therapy to the liver in the setting of metastatic intrahepatic cholangiocarcinoma may improve overall survival. Objective: To compare the overall survival of patients with metastatic intrahepatic cholangiocarcinoma treated with chemotherapy alone vs chemotherapy with definitive liver-directed local therapy. Design, Setting, and Participants: This cohort study used the National Cancer Database to identify 2201 patients with metastatic intrahepatic cholangiocarcinoma diagnosed between January 2004 and December 2014 who received chemotherapy with or without hepatic surgery or external beam radiation to a dose 45 Gy or higher. Multiple imputation, Cox proportional hazards, propensity score matching, and landmark analysis were used to adjust for confounding variables. Analyses were performed between September 2018 and February 2019. Exposures: Chemotherapy alone and chemotherapy with liver-directed surgery or radiation. Main Outcomes and Measures: Overall survival. Results: A total of 2201 patients (1131 [51.4%] male; median [interquartile range] age, 63 [55-71] years) who received chemotherapy alone (2097 [95.3%]) or chemotherapy with liver-directed local therapy (total, 104 [4.7%]; surgery, 76 [73.1%]; radiation, 28 [26.9%]) were identified. Patients treated with chemotherapy alone had larger median (interquartile range) primary tumor size (7.0 [4.4-10.0] cm vs 5.6 [4.0-8.3] cm; P = .048) and higher frequency of lung metastases (383 [25.9%] vs 7 [6.7%]; P = .004). Patients treated with liver-directed local therapy had higher frequency of distant lymph node metastases (34 [32.7%] vs 528 [25.2%]; P = .045). Liver-directed local therapy was associated with higher overall survival compared with chemotherapy alone on multivariable analysis (hazard ratio [HR], 0.60; 95% CI, 0.48-0.74; P < .001). A total of 208 patients treated with chemotherapy alone were propensity score matched with 104 patients treated with chemotherapy plus liver-directed local therapy. Liver-directed local therapy continued to be associated with higher overall survival (HR, 0.57; 95% CI, 0.44-0.74; P < .001), which persisted on landmark analysis at 3 months (HR, 0.61; 95% CI, 0.47-0.79; log-rank P < .001), 6 months (HR, 0.68; 95% CI, 0.50-0.92; log-rank P = .01), and 12 months (HR, 0.68; 95% CI, 0.47-0.98; log-rank P = .04). Conclusions and Relevance: In this study, the addition of hepatic surgery or irradiation to chemotherapy was associated with higher overall survival when compared with chemotherapy alone in patients with metastatic intrahepatic cholangiocarcinoma. These findings may be valuable given the paucity of available data for this disease and should be validated in an independent cohort or prospective study.

Survival after radiotherapy vs. radical prostatectomy for unfavorable intermediate-risk prostate cancer.

BACKGROUND: The optimal treatment for unfavorable intermediate-risk prostate cancer is unknown. Given the lack of randomized evidence, large comparative studies may be useful in guiding clinical decision-making. METHODS: We queried the National Cancer Database for patients with unfavorable intermediate-risk prostate cancer, as defined by the National Comprehensive Cancer Network. We compared overall survival between patients treated with radical prostatectomy (RP), external beam radiation therapy (EBRT), brachytherapy, and EBRT plus brachytherapy (EBRT+BT) using Cox proportional hazards models and propensity score matching. RESULTS: A total of 10,439 patients were analyzed. There was no statistically significant difference in overall survival between RP and EBRT+BT (hazard ratio [HR] = 1.24; 95% confidence interval [CI] 0.58-2.65). RP was associated with higher survival when compared to EBRT (HR = 2.30, 95% CI 1.70-3.20) and brachytherapy (HR = 2.90, 95% CI 1.40-6.20). When accounting for androgen deprivation therapy (ADT), there was no statistically significant difference in survival between RP and brachytherapy with ADT (HR = 3.08; 95% CI 0.62-15.27) or EBRT to a dose of ≥7920 cGy with ADT (HR = 2.6, 95% CI 0.50-13.20). CONCLUSION: We found no statistically significant difference in survival between RP and EBRT+BT. EBRT and brachytherapy had higher mortality, respectively, compared to RP. When including only radiotherapy patients who received ADT and, in the case of EBRT, a total dose ≥ 7920 cGy, there was no statistically significant difference in survival when comparing RP to EBRT or brachytherapy. These findings should be prospectively studied.

Stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC): contemporary insights and advances.

The standard-of-care treatment for early-stage non-small cell lung cancer (NSCLC) continues to be surgery in the form of lobectomy or pneumonectomy. Stereotactic body radiation therapy (SBRT) has evolved as a viable alternative to surgery for medically inoperable patients, achieving excellent local control (LC) with relatively minimal toxicity in standard-risk patients. Nevertheless, the maturation of SBRT has fostered debate regarding its use, technique, dose, and fractionation, particularly in the context of patient- and disease-specific characteristics such as tumor size and location. This review will cover the recent trends and future directions of SBRT as it becomes an increasingly individualized modality in the treatment of early-stage NSCLC.