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Highlights • Stereotactic radiation was used for both lung cancer primaries and brain metastases. • Oligometastatic and stage I patients achieved similar survival and local control. • Both patient groups had low toxicity rates. • Local radiation alone is effective and safe for oligometastatic lung cancer., Background There is increasing interest in treating oligometastatic non-small cell lung cancer (NSCLC) patients with stereotactic radiation. We aimed to address whether patients definitively treated with synchronous thoracic stereotactic body radiation therapy (SBRT) and brain stereotactic radiosurgery (SRS) had favorable outcomes with local therapy. Materials and methods We reviewed a database of patients receiving lung SBRT as well as a database for brain metastasis patients treated with SRS between June 2004 and January 2016. We selected for cT1-2aN0M1 NSCLC patients with brain metastases and calculated their overall survival (OS), freedom from progression (FFP), and local control (LC) rates. Results Six patients had oligometastatic NSCLC with 1–3 synchronous brain metastases treated with lung SBRT and brain SRS. No patients received immunotherapy and two-thirds did not receive systemic therapy. Median follow-up was 9 months for the entire cohort (range, 2–95 months) and 95 months for the surviving patient. Median OS was 12.4 months (95% confidence interval [CI], 7–18 months). At 1 year, patients had 67% OS (95% CI, 29–100%), 17% FFP (95% CI, 0–46%), and 100% LC. Their brain disease had 80% 1-year LC (95% CI, 45–100%) and 53% 1-year FFP (95% CI, 5–100%). Two patients had no distant progression, two had brain progression, one had adrenal gland progression, and one had bone and liver progression. Conclusion In patients presenting with oligometastatic lung cancer limited to the brain, treatment with both lung SBRT and brain SRS achieves good LC of all sites with encouraging OS.

BACKGROUND: Patients with multiple primary lung cancers (MPLC) increasingly receive multiple courses of stereotactic body radiation therapy (SBRT). We aimed to clarify the efficacy and safety of such treatments. PATIENTS AND METHODS: We reviewed a prospective lung SBRT database for patients treated for stage I non-small cell lung cancer between June 2004 and December 2015. RESULTS: 374 patients received a single course of SBRT, 14 received synchronous SBRT, 48 received metachronous SBRT alone, and 108 received surgery and metachronous SBRT. Median follow-up was 37.0 months for survivors. Patients that received a single course had a three-year overall survival (OS) of 54.2% (95% confidence interval [CI], 48.8–59.3%), three-year freedom from progression (FFP) of 67.3% (95% CI, 60.9–72.9), and grade ≥3 toxicity of 3.5%. Compared to single-course patients, patients receiving metachronous SBRT alone and patients receiving surgery and metachronous SBRT had improved OS (79.7% [95% CI, 64.4–88.9%], P

Purpose/Objectives Before definitive stereotactic body radiation therapy (SBRT) for presumably node-negative, early-stage NSCLC, many patients are staged with PET/CT alone. In patients undergoing PET/CT prior to SBRT, the role of invasive nodal staging (INS) with endobronchial ultrasound (EBUS) or mediastinoscopy is uncertain. We sought to characterize the impact of nodal staging modality on outcomes. Materials/Methods Patients receiving definitive SBRT for T1-2N0 NSCLC deemed node-negative by either PET/CT plus INS (EBUS or mediastinoscopy) or PET/CT alone were identified. Patients with initially equivocal or positive nodes on PET/CT were excluded from this analysis. All patients received 3–5 fraction SBRT according to institutional guidelines. Control was assessed by at least one follow-up CT in all patients. Multivariable logistic regression (MVA) was performed to identify variables independently associated with use of INS. Results We identified 651 eligible patients at our institution from 2005–2016. INS was performed in 15.2% of patients (n = 99) with EBUS (n = 78) or mediastinoscopy (n = 21). Median follow-up was 19.4 months (0.2–135.1). Median survival was 28.5 months (0.6–140). Factors predictive of increased likelihood of INS after negative PET/CT on MVA were age (OR for decreasing age 1.033; 95% CI 1.058–1.010), Caucasian race (OR vs. non-white 1.852; 1.044–3.289), male sex (1.629; 1.031–2.575), central location (1.978; 1.218–3.211) and squamous histology (2.564; 1.243–5.287). Nodal and/or distant control at 2 years was similar between PET/CT alone (78%, 95% CI 74–82%) and INS + PET/CT (75%, 95% CI 65–85%) (p = 0.877) as well as on MVA. Overall survival did not differ based on staging modality. Conclusions In patients with early-stage NSCLC deemed node-negative by PET/CT, addition of INS did not appreciably alter patterns of failure or survival after definitive SBRT. This study does not question the established value of INS for equivocal or suspicious nodes.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic neoplasm resulting from the malignant transformation of T-cell progenitors, and comprises approximately 15% and 25% of pediatric and adult ALL cases respectively. It is well-established that activating NOTCH1 mutations are the major genetic lesions driving T-ALL in most patients, but efforts to develop targeted therapies against this pathway have produced limited success in decreasing leukemic burden and come with significant clinical side effects. A finer detailed understanding of the genetic and molecular mechanisms underlying T-ALL is required identify patients at increased risk for treatment failure and the development of precision medicine strategies. Generation of genetic models that more accurately reflect the normal developmental history of T-ALL are necessary to identify new avenues for treatment. The DNA methyltransferase enzyme DNMT3A is also recurrently mutated in T-ALL patients, and we show here that inactivation of Dnmt3a combined with Notch1 gain-of-function leads to an aggressive T-ALL in mouse models. Moreover, conditional inactivation of Dnmt3a in mouse hematopoietic cells leads to an accumulation of immature progenitors in the thymus which are less apoptotic. These data demonstrate that Dnmt3a is required for normal T-cell development, and acts as a T-ALL tumor suppressor.

Purpose Optimal management of isolated local recurrences after stereotactic body radiation therapy (SBRT) for early non-small cell lung cancer (NSCLC) is unknown and literature describing repeat SBRT for in-field recurrences after initial SBRT are sparse. We investigate the safety and efficacy of salvage SBRT for isolated local failures after initial SBRT for NSCLC. Methods/Materials Patients receiving SBRT for isolated local recurrence after initial SBRT for early NSCLC were identified using a prospective registry. Both courses were 3–5 fractions with a biologically effective dose (BED10) of ≥100 Gy. Local failure was defined as within 1 cm of the initial planning target volume (PTV) or an overlap of the ≥25% isodose lines of the first and second treatments. Failures >1 cm beyond the PTV and without ≥25% overlap, or with additional recurrence sites were excluded. Kaplan-Meier analysis was used to estimate survival. Results A total 21 patients receiving salvage SBRT from 2008 to 2017 were identified. Median interval from initial SBRT to salvage SBRT was 23 months (7–52). Six patients (29%) had central tumors. Median follow-up time from salvage SBRT was 24 months (3–60). Median overall survival after salvage was 39 months. After reirradiation, two-year primary tumor control was 81%, regional nodal control was 89%, distant control was 75% and overall survival was 68%. Grade 2 pneumonitis occurred in 2 patients (10%) and grade 2 chest wall toxicity in 4 patients (19%). No grade 3+ toxicity was observed. Conclusions Salvage SBRT for isolated local failures after initial SBRT appears safe, with low treatment-related toxicity and encouraging rates of tumor control.