Eric D. Brooks

7-year follow-up after stereotactic ablative radiotherapy for patients with stage I non–small cell lung cancer: Results of a phase 2 clinical trial

The authors evaluated the efficacy, patterns of failure, and toxicity of stereotactic ablative radiotherapy (SABR) for patients with medically inoperable, clinical stage I non–small cell lung cancer (NSCLC) in a prospective clinical trial with 7 years of follow‐up. Clinical staging was performed according to the seventh edition of the American Joint Committee on Cancer TNM staging system.

Long-Term Outcomes of Salvage Stereotactic Ablative Radiotherapy for Isolated Lung Recurrence of Non–Small Cell Lung Cancer: A Phase II Clinical Trial

Objectives: Our goal was to evaluate stereotactic ablative radiotherapy (SABR) as a salvage option for isolated recurrence of NSCLC in the lung parenchyma after definitive treatment of stage I to III disease. Methods: Patients who had histologically confirmed, positron emission tomography–staged, isolated NSCLC recurring locally or metastasis in the lung parenchyma (≤3 cm, suitable for SABR) after previous definitive treatment were prospectively enrolled in this trial and treated with volumetric, image‐guided SABR to 50 Gy in four fractions. Patients were then followed with computed tomography or positron emission tomography/computed tomography. Primary end points included the pattern of failure after salvage SABR, overall survival (OS), and progression‐free survival (PFS). Results: Fifty‐nine patients with recurrent disease were treated with salvage SABR. The median age was 70 years (range 45–86 years), and the median follow‐up time after salvage SABR was 58.3 months. Re‐recurrence after salvage SABR developed in 19 patients (32%). Measuring from the date of salvage SABR, the estimated 5‐year rates of local, regional, and distant failure were 5.2%, 10.3%, and 22.4%, respectively; the estimated PFS was 46.2% at 3 years and 41.1% at 5 years; and the OS rates were 63.5% at 3 years and 56.5% at 5 years. A high post‐SABR neutrophil‐to‐lymphocyte ratio was found to predict poor survival. Grade 3 treatment‐related adverse events developed in three patients (5%). No patient had a grade 4 or 5 event. Conclusion: Our study showed that salvage SABR provides excellent 5‐year OS, local control, and PFS rates with minimal toxicity for patients with isolated NSCLC recurrence in the lung parenchyma. These results are striking and comparable to historically reported outcomes of patients with primary early‐stage NSCLC treated with definitive SABR. SABR appears to be a very effective and safe salvage option for patients with isolated lung parenchyma recurrent disease after definitive treatment and should be considered along with surgery as a potential first‐line option for patients with local lung parenchymal recurrent disease.

Uncovering the immune tumor microenvironment in non-small cell lung cancer to understand response rates to checkpoint blockade and radiation

The study of immunology has led to breakthroughs in treating non-small cell lung cancer (NSCLC). The recent approval of an anti-PD1 checkpoint drug for NSCLC has generated much interest in novel combination therapies that might provide further benefit for patients. However, a better understanding of which combinations may (or may not) work in NSCLC requires understanding the lung immune microenvironment under homeostatic conditions and the changes in that microenvironment in the setting of cancer progression and with radiotherapy. This review provides background information on immune cells found in the lung and the prognostic significance of these cell types in lung cancer. It also addresses current clinical directions for the combination of checkpoint inhibitors with radiation for NSCLC.

Chemoradiotherapy Versus Chemotherapy Alone for Unresected Nonmetastatic Gallbladder Cancer: National Practice Patterns and Outcomes

Purpose: Current guidelines recommend chemotherapy (CT) with or without radiotherapy for unresected nonmetastatic gallbladder cancer (GC), with little consensus. However, several small-volume, single-institution studies have documented the efficacy of local therapy for this population. This is the largest study to date evaluating outcomes of chemoradiotherapy (CRT) versus CT alone in unresected nonmetastatic GC. Methods: The National Cancer Database was queried for primary GC cases (2004-2013) receiving CT alone or CRT. Patients receiving resection or lack of CT were excluded, as were those with metastatic disease or unknown M classification. Logistic regression analysis ascertained factors associated with CRT delivery. Kaplan-Meier analysis evaluated overall survival (OS) between both cohorts. Cox proportional hazards modeling determined variables associated with OS. Results: In total, 1,199 patients were analyzed (CRT: n=327, 27%; CT: n=872, 73%). Groups were evenly balanced, with no factor on multivariate logistic regression analysis statistically predicting for receipt of a particular paradigm. Median OS in the CRT and CT groups was 12.9 versus 7.8 months, respectively (P=.001). On multivariate analysis, OS was associated with age and years of treatment (P=.001 each). Notably, receipt of CRT independently predicted for improved OS (P=.001). Conclusions: CRT, compared with CT alone, was independently associated with improved survival in unresected nonmetastatic GC. Although causation is not implied, these results support the necessity for prospective CRT evaluation.

Development of a Transcriptomic Signature Associated With Lung Adenocarcinoma Recurrence and Survival

Materials/Methods: Eighteen patients with 38 synchronous or metachronous lung nodules were treated between 2010 and 2016 at a tertiary hospital with SBRT. Demographic and clinicopathologic data as well as dosimetry for target volume coverage and organs at risk were collected. Pre-treatment, acute (<90 days), and late (>90 days) toxicities were retrospectively reviewed using standardized CTCAE 4.0 criteria. Radiographic and clinical pneumonitis was recorded. Local control (treatment field and ipsilateral lobe), regional control (ipsilateral lung or mediastinum), metastasis-free survival, progression-free survival, and overall survival were calculated. Results: Sixteen patients received SBRT to 2 sites, while two patients were treated at 3 sites. Six patients were treated for synchronous tumors, while 12 patients were treated for metachronous tumors. The median age at first treatment was 77 years (IQR: 68.5-79.8) and for metachronous lesions the median time interval between SBRT courses was 14.2 months (95% CI: 6.8-21.6). The majority (76.3%) of the treated nodules were primary lung tumors, while 23.7% were metastatic nodules of varying histologies. Forty percent of second or third SBRT courses were to nodules in the contralateral lung, while 40% were to nodules in the same lobe. The most common fractionation scheme was 50Gy in 5 fractions (cumulative range: 3000-6000 in 3-8 fractions). The mean treated nodule size was 2.0 cm (95% CI: 1.6-2.4). At median follow-up of 56.0 months from initial SBRT, local failure occurred in 10.8% of lesions. Median overall survival was 31.8 months (95% CI: 27.6-47.2) while median progression-free survival was 25.7 months (95% CI: 17.2-34.1). Six patients (16.6%) developed grade 1 pneumonitis, two patients (11.1%) developed grade 2 pneumonitis after their first SBRT course, while one patient (5.5%) developed grade 3 pneumonitis after her second course of SBRT. Conclusion: SBRT to synchronous or metachronous pulmonary malignancies appears to yield oncologic and toxicity outcomes similar to solitary lesion SBRT. Receipt of previous SBRT should not preclude consideration of further SBRT. Author Disclosure: C. Goodman: None.